Effect of transforming growth factor-beta1 on embryonic and posthatch muscle growth and development in normal and low score normal chicken.

PubMed

Li, X; Velleman, S G

2009-02-01

During skeletal muscle development, transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of muscle cell proliferation and differentiation. The TGF-beta1 signal is carried by Smad proteins into the cell nucleus, inhibiting the expression of key myogenic regulatory factors including MyoD and myogenin. However, the molecular mechanism by which TGF-beta1 inhibits muscle cell proliferation and differentiation has not been well documented in vivo. The present study investigated the effect of TGF-beta1 on in vivo skeletal muscle growth and development. A chicken line, Low Score Normal (LSN) with reduced muscling and upregulated TGF-beta1 expression, was used and compared to a normal chicken line. The injection of TGF-beta1 at embryonic day (ED) 3 significantly reduced the pectoralis major (p. major) muscle weight in the normal birds at 1 wk posthatch, whereas no significant difference was observed in the LSN birds. The difference between normal and LSN birds in response to TGF-beta1 is likely due to different levels of endogenous TGF-beta1 where the LSN birds have increased TGF-beta1 expression in their p. major muscle at both 17 ED and 6 wk posthatch. Smad3 expression was reduced by TGF-beta1 from 10 ED to 1 wk posthatch in normal p. major muscle. Unlike Smad3, Smad7 expression was not significantly affected by TGF-beta1 until posthatch in both normal and LSN p. major muscle. Expression of MyoD was reduced 35% by TGF-beta1 during embryonic development in normal p. major muscle, whereas LSN p. major muscle showed a delayed decrease at 1 d posthatch in MyoD expression in response to the TGF-beta1 treatment. Myogenin expression was reduced 29% by TGF-beta1 after hatch in normal p. major muscle. In LSN p. major muscle, TGF-beta1 treatment significantly decreased myogenin expression by 43% at 1 d posthatch and 32% at 1 wk posthatch. These data suggested that TGF-beta1 reduced p. major muscle growth by inhibiting MyoD and myogenin expression during both embryonic and posthatch development. Furthermore, TGF-beta1 also reduced the expression of the cell adhesion receptor beta1 integrin subunit during embryonic and posthatch muscle growth in normal and LSN chickens. Therefore, the reduction of beta1 integrin in response to TGF-beta1 is also associated with decreased posthatch muscle growth. The results from this study indicate that TGF-beta1 inhibits skeletal muscle growth by regulating MyoD and myogenin expression. These data also suggest that a beta1 integrin-mediated alternative pathway is likely involved in the TGF-beta1-induced reduction of muscle growth.

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

Test performance of blood beta-glucan for Pneumocystis jirovecii pneumonia in patients with AIDS and respiratory symptoms.

PubMed

Wood, Brian R; Komarow, Lauren; Zolopa, Andrew R; Finkelman, Malcolm A; Powderly, William G; Sax, Paul E

2013-03-27

The objective of this study was to define the test characteristics of plasma beta-glucan for diagnosis of Pneumocystis jirovecii pneumonia (PCP) in AIDS patients with respiratory symptoms. Analysis of baseline blood samples in a randomized strategy study of patients with acute opportunistic infections, limited to participants with respiratory symptoms. Participants in the 282-person ACTG A5164 trial had baseline plasma samples assayed for beta-glucan testing. As part of A5164 trial, two study investigators independently adjudicated the diagnosis of PCP. Respiratory symptoms were identified by investigators from a list of all signs and symptoms with an onset or resolution in the 21 days prior to or 14 days following study entry. Beta-glucan was defined as positive if at least 80 pg/ml and negative if less than 80 pg/ml. Of 252 study participants with a beta-glucan result, 159 had at least one respiratory symptom, 139 of whom had a diagnosis of PCP. The sensitivity of beta-glucan for PCP in participants with respiratory symptoms was 92.8% [95% confidence interval (CI) 87.2-96.5], and specificity 75.0% (95% CI 50.9-91.3). Among 134 individuals with positive beta-glucan and respiratory symptoms, 129 had PCP, for a positive predictive value of 96.3% (95% CI 91.5-98.8). Fifteen of 25 patients with a normal beta-glucan did not have PCP, for a negative predictive value of 60% (95% CI 38.7-78.9). Elevated plasma beta-glucan has a high predictive value for diagnosis of PCP in AIDS patients with respiratory symptoms. We propose an algorithm for the use of beta-glucan as a diagnostic tool on the basis of the pretest probability of PCP in such patients.

Gaucher disease types 1, 2, and 3: differential mutations of the acid beta-glucosidase active site identified with conduritol B epoxide derivatives and sphingosine.

PubMed Central

Grabowski, G A; Dinur, T; Osiecki, K M; Kruse, J R; Legler, G; Gatt, S

1985-01-01

To elucidate the genetic heterogeneity in Gaucher disease, the residual beta-glucosidase in cultured fibroblasts from affected patients with each of the major phenotypes was investigated in vitro and/or in viable cells by inhibitor studies using the covalent catalytic site inhibitors, conduritol B epoxide or its bromo derivative, and the reversible cationic inhibitor, sphingosine. These studies delineated three distinct groups (designated A, B, and C) of residual activities with characteristic responses to these inhibitors. Group A residual enzymes had normal I50 values (i.e., the concentration of inhibitor that results in 50% inhibition) for the inhibitors and normal or nearly normal t1/2 values for conduritol B epoxide. All neuronopathic (types 2 and 3) and most non-Jewish nonneuronopathic (type 1) patients had group A residual activities and, thus, could not be distinguished by these inhibitor studies. Group B residual enzymes had about four- to fivefold increased I50 values for the inhibitors and similarly increased t1/2 values for conduritol B epoxide. All Ashkenazi Jewish type 1 and only two non-Jewish type 1 patients had group B residual activities. The differences in I50 values between groups A and B also were confirmed by determining the uninhibited enzyme activity after culturing the cells in the presence of bromo-conduritol B epoxide. Group C residual activity had intermediate I50 values for the inhibitors and represented a single Afrikaner type 1 patient: this patient was a genetic compound for the group A (type 2) and group B (type 1) mutations. These inhibition studies indicated that: Gaucher disease type 1 is biochemically heterogeneous, neuronopathic and non-Jewish nonneuronopathic phenotypes cannot be reliably distinguished by these inhibitor studies, and the Ashkenazi Jewish form of Gaucher disease type 1 results from a unique mutation in a specific active site domain of acid beta-glucosidase that leads to a defective enzyme with a decreased Vmax. PMID:4003396

Improving the chi-squared approximation for bivariate normal tolerance regions

NASA Technical Reports Server (NTRS)

Feiveson, Alan H.

1993-01-01

Let X be a two-dimensional random variable distributed according to N2(mu,Sigma) and let bar-X and S be the respective sample mean and covariance matrix calculated from N observations of X. Given a containment probability beta and a level of confidence gamma, we seek a number c, depending only on N, beta, and gamma such that the ellipsoid R = (x: (x - bar-X)'S(exp -1) (x - bar-X) less than or = c) is a tolerance region of content beta and level gamma; i.e., R has probability gamma of containing at least 100 beta percent of the distribution of X. Various approximations for c exist in the literature, but one of the simplest to compute -- a multiple of the ratio of certain chi-squared percentage points -- is badly biased for small N. For the bivariate normal case, most of the bias can be removed by simple adjustment using a factor A which depends on beta and gamma. This paper provides values of A for various beta and gamma so that the simple approximation for c can be made viable for any reasonable sample size. The methodology provides an illustrative example of how a combination of Monte-Carlo simulation and simple regression modelling can be used to improve an existing approximation.

Transforming growth factor-beta and nitrates in epithelial ovarian cancer.

PubMed

Khalifa, A; Kassim, S K; Ahmed, M I; Fayed, S T

1999-12-01

The role of transforming growth factor-beta (TGF-beta) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-beta by enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-beta, nitrate, and SPF were significant among different groups (X2 = 12.01, P = 0.0025, X2 = 67.42, P = 0.000, X2 = 9.06, P = 0.011 respectively). Nitrate mean ranks were significant among different FIGO stages of the disease (X2 = 17.6, P = 0.000). A significant correlation was shown between TGF-beta, and nitrate levels in all tissues (r = 0.24, P = 0.01), as well as in malignant tissues (r = 0.3, P = 0.026). Cutoff values were determined for both TGF-beta (290 pg/mg protein), and nitrates (310 nmole/mg non protein nitrogenous substances). At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-beta had 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-beta above the cut-off had worse prognosis (X2 = 12.69, P = 0.004). The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-beta and NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-beta could be of prognostic significance.

Study of long term structural and functional changes in medically controlled glaucoma

PubMed Central

Pandey, Achyut N; Sujata, S

2014-01-01

AIM Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. METHODS Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. RESULTS A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. CONCLUSION Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide. PMID:24634878

Study of long term structural and functional changes in medically controlled glaucoma.

PubMed

Pandey, Achyut N; Sujata, S

2014-01-01

Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide.

Proinflammatory cytokine activities, matrix metalloproteinase-3 activity, and sulfated glycosaminoglycan content in synovial fluid of dogs with naturally acquired cranial cruciate ligament rupture.

PubMed

Fujita, Yukihiro; Hara, Yasushi; Nezu, Yoshinori; Schulz, Kurt S; Tagawa, Masahiro

2006-06-01

To measure and compare activities of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and matrix metalloproteinase-3 (MMP-3); as well as sulfated glycosaminoglycan (S-GAG) content in synovial fluid from dogs with cranial cruciate ligament rupture (CCLR) and dogs with clinically normal stifles. To determine whether correlations exist between demographic and disease-related variables and these synovial markers. Prospective clinical study. Dogs with CCLR (n=23) and Beagles with normal stifle joints (n=21). Synovial fluid activities of proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) were determined by bioassay. MMP-3 activity was measured using fluorogenic substrate. S-GAG contents were determined by dimethylmethylene blue dye-binding assay. Mann-Whitney U-test was used to compare results from CCLR joints with normal controls. Spearman's rank correlation test was used to evaluate associations between demographic and disease-related markers and synovial markers. Mean values for synovial markers were significantly higher in CCLR joints compared with controls. IL-1beta and MMP-3 were positively correlated with lameness duration. Activities of proinflammatory cytokines, MMP-3 activity and S-GAG contents were significantly elevated in synovial fluid from canine stifle joints with naturally acquired CCLR. These results indicate that there is joint inflammation and increased release of GAGs into synovial fluid, suggesting that these inflammatory changes are associated with depletion of proteoglycan from articular cartilage. Medical and surgical treatments designed to decrease joint inflammation and breakdown of proteoglycans may be of value in the management of CCLR in the dog.

Changes in the turbulent boundary layer structure associated with net drag reduction by outer layer manipulators

NASA Technical Reports Server (NTRS)

Rashidnia, N.; Falco, R. E.

1987-01-01

A specially designed wind tunnel was used to examine the effects of tandemly arranged parallel plate manipulators (TAPPMs) on a turbulent boundary-layer structure and the associated drag. Momentum balances, as well as measurements of the local shear stress from the velocity gradient near the wall, were used to obtain the net drag and local skin friction changes. Two TAPPMs, identical except for the thickness of their plates, were used in the study. Results with .003 inch plates were a maximum net drag reduction of 10 percent at 58 beta sub o (using a momentum balance). At 20 beta sub o, simultaneous laser sheet flow visualization and hot-wire anemometry data showed that the Reynolds stress in the large eddies was significantly reduced, as were the streamwise and normal velocity components. Using space-time correlations the reductions were again identified. Furthermore, quantitative flow visualization showed that the outward normal velocity of the inner region was also significantly decreased in the region around 20 beta sub o. However, throughout the first 130 beta sub o, the measured sublayer thickness with the TAPPMs in place was 15 to 20 percent greater. The data showed that the skin friction, as well as the structure of the turbulence, was strongly modified in the first 35 beta sub o, but that they both significantly relaxed toward unmanipulated boundary layer values by 50 beta sub o.

Direct and indirect markers of cartilage metabolism in synovial fluid obtained from dogs with hip dysplasia and correlation with clinical and radiographic variables.

PubMed

Fujita, Yukihiro; Hara, Yasushi; Nezu, Yoshinori; Yamaguchi, Shinya; Schulz, Kurt S; Tagawa, Masahiro

2005-12-01

To compare activities of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and matrix metalloproteinase (MMP)-3 and contents of sulfated glycosaminoglycan (S-GAG) in joint fluid obtained from dogs with hip dysplasia (HD) and clinically normal dogs, evaluate correlations among these markers in joint fluid obtained from dogs with HD, and evaluate correlations between each marker and clinical and radiographic variables. Animals-26 dogs with HD (clinical group) and 43 clinically normal Beagles (control group). Joint fluid was aseptically collected from the hip joints of all dogs. For each dog in the clinical group, age, duration of lameness, radiographic osteoarthritis (OA) score, and Norberg angle in each affected joint were recorded. Activities of IL-1beta, IL-6, TNF-alpha, and MMP-3 and S-GAG contents were measured. Values were compared between groups by use of Mann-Whitney U tests, and the Spearman rank correlation test was used to evaluate correlations among markers and between each marker and clinical or radiographic variables. Values of all markers were significantly higher for the clinical group, compared with values for the control group. There was a moderate positive correlation between lameness duration and IL-6 activity and a strong negative correlation between the Norberg angle and IL-1beta activity. Analysis of our results indicated that there was a significant increase in markers of OA in dogs with HD. Activities of IL-1beta and IL-6 in joint fluid of dogs with HD may be influenced by the severity of laxity in the hip joint and lameness duration, respectively.

Expression of alpha and beta subunit isoforms of Na,K-ATPase in the mouse inner ear and changes with mutations at the Wv or Sld loci.

PubMed

Schulte, B A; Steel, K P

1994-07-01

Mice homozygous for mutations at the viable dominant spotting (Wv) and Steel-dickie (Sld) loci exhibit a similar phenotype which includes deafness. The auditory dysfunction derives from failure of the stria vascularis to develop normally and to generate a high positive endocochlear potential (EP). Because strial function is driven by Na,K-ATPase its expression was investigated in inner ears of Wv/Wv and Sld/Sld mice and their wild-type littermates by immunostaining with antisera against four of the enzyme's subunit isoforms. Wild-type mice from two different genetic backgrounds showed an identical distribution of subunit isoforms among inner ear transport cells. Several epithelial cell types coexpressed the alpha 1 and beta 1 subunits. Vestibular dark cells showed no reactivity for beta 1 but expressed abundant beta 2, whereas, strial marginal cells stained strongly for both beta isoforms. The only qualitative difference between mutant and wild-type mice was the absence of beta 1 subunit in marginal cells of the mutant's stria. However, it is unlikely that this difference accounts for failure of mutants to generate a high EP because the beta 1 subunit is not present in the stria vascularis of either rats or gerbils with normal EP values. Strong immunostaining for Na,K-ATPase in lateral wall fibrocytes of normal mice along with diminished immunoreactivity in the mutants supports the concept that these strategically located transport fibrocytes actively resorb K+ leaked across Reissner's membrane into scala vestibuli or effluxed from hair cells and nerves into scala tympani. It is further speculated that the resorbed K+ normally is siphoned down its concentration gradient into the intrastrial space through gap junctions between fibrocytes and strial basal and intermediate cells where it is recycled back to endolymph via marginal cells. Thus, failure of mutants to generate a positive EP could be explained by the absence of intermediate cells which may form the final link in the conduit for moving K+ from perilymph to the intrastrial compartment.

A model for hematopoietic death in man from irradiation of bone marrow during radioimmunotherapy.

PubMed

Scott, B R; Dillehay, L E

1990-11-01

There are numerous institutions worldwide performing clinical trials of radioimmunotherapy (RIT) for cancer. For RIT, an exponentially decaying radionuclide is attached by using a chelating agent to a specific monoclonal or polyclonal tumour antibody (e.g. antiferritin IgG). The major limitation to RIT is toxicity to normal tissue in organs other than the one containing the tumour (e.g. bone marrow). The focus of this manuscript is on modelling the risk (or probability) of hematopoietic death in man for exponentially decaying patterns of high-energy beta irradiation (e.g. 90Y) of bone marrow by radioimmunoglobulin injected into the blood. The analytical solutions presented are only applicable to protocols for which significant uptake of radioactivity by the bone marrow does not occur, and only for high energy beta emitters. However, the generic equation used to obtain the analytical solutions is applicable to any continuous pattern of high energy beta irradiation. A model called the "normalized dose model" was used to generate calculated values for the LD50 as a function of the effective half-time for the radioimmunoglobulin in the blood. A less complicated empirical model was used to describe the calculated values. This model is presumed to be valid for effective half-times in blood of up to about 20 days. For longer effective half-times, the LD50 can be estimated using the normalized-dose model presented. In this manuscript, we also provide a modified Weibull model that allows estimation of the risk of hematopoietic death for single or multiple injections (in one cycle) of radioimmunoglobulin, for patients with normal susceptibility to irradiation and for patients with heightened susceptibility. With the modified Weibull model, the risk of hematopoietic death depends on the level of medical treatment provided to mitigate radiation injuries.

Canine serum protein patterns using high-resolution electrophoresis (HRE).

PubMed

Abate, O; Zanatta, R; Malisano, T; Dotta, U

2000-03-01

Serum protein values were determined in 26 healthy dogs using agarose gel electrophoresis (SPE), splitting the electrophoretic separation into six regions: albumin, alpha(1), alpha(2), beta(1), beta(2)and gamma globulins. High-resolution electrophoresis (HRE) was used to separate single proteins. Serum proteins from dogs (26 healthy and 20 affected by various diseases) were then characterized by electrophoretic immunofixation (IFE) and Sudan black staining on HRE film. Haemoglobin and normal canine plasma and serum were used to identify haptoglobin and fibrinogen, respectively. In the standard pattern, determined by HRE, the following proteins were identified: albumin, alpha(1)-lipoprotein (alpha(1)-region), haptoglobin and alpha(2)-macroglobulin (alpha(2)-region), beta -lipoprotein and C3 (beta(1)-region), transferrin and IgM (beta(2)-region), IgG (mostly in gamma -region and partly in beta(2)-region). The HRE pattern shown by healthy dogs could be compared with those of dogs affected by various diseases to obtain clinical information. Copyright 2000 Harcourt Publishers Ltd.

Maternal serum free-beta-chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency thickness at 10-13(+6) weeks in relation to co-variables in pregnant Saudi women.

PubMed

Ardawi, Mohammed-Salleh M; Nasrat, Hasan A; Rouzi, Abdulrahim A; Qari, Mohammed H; Al-Qahtani, Mohammed H; Abuzenadah, Adel M

2007-04-01

To establish normative values and distribution parameters of first-trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13(+6) weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free beta-hCG and PAPP-A were determined at 10 to 13(+6) weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free beta-hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r = -0.296) or parity (r = -0.311), whereas both free beta-hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free beta-hCG in female fetuses. Smoking decreased MoM values of free beta-hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free beta-hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in each case). MoM values (body weight-corrected) of free beta-hCG were 25.2% higher in Africans and 19.4% higher in Orientals but 6.8% lower in other Arabian and Asian (by 5.8%) women as compared to Saudi women (P < 0.05; in each case). The normative values and distribution parameters for fetal NT, maternal serum free beta-hCG and PAPP-A were established in Saudi singleton pregnancies, the maternal body weight together with smoking, twin pregnancy and ethnicity being important first-trimester screening co-variables. Gravidity, parity and fetal gender are also considered to influence one or more of the first-trimester markers examined. Copyright (c) 2007 John Wiley & Sons, Ltd.

Prognostic value of repeated serum CA 125 measurements in first trimester pregnancy.

PubMed

Schmidt, T; Rein, D T; Foth, D; Eibach, H W; Kurbacher, C M; Mallmann, P; Römer, T

2001-08-01

To assess the diagnostic value of maternal CA 125 in patients with symptomatic first trimester pregnancy and to evaluate the prognostic significance of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat, complicated by vaginal bleeding. Two prospective open-label studies with longitudinal follow-up in the second trial. Academic Department of Obstetrics and Gynecology, University of Cologne. Study 1: 168 patients presenting between gestational weeks 6 and 12 with: extrauterine pregnancy, 29; missed abortion, 50; incomplete spontaneous abortion, 38; imminent abortion, 33; and normal pregnancy (no history of endometriosis or ovarian mass), 18. Study 2: Fifty consecutive patients with vaginal bleeding during gestational weeks 6-12 all of whom having demostrable fetal heartbeat. Eighteen patients finally aborted whereas the remainder had normally continuing pregnancy until term. Study 1: Single serum determinations of CA 125 and beta-hCG were correlated with the different disorders observed. Study 2: Two sequential measurements of serum CA 125 and beta-hCG performed within a 5-7 days interval were related to the outcome of pregnancy as indicated by changes of the ultrasound presentation, miscarriage, future hospitalization, or delivery. Study 1: Patients with vaginal bleeding generally had higher median CA 125 values (38 IU/ml; range 1.3-540) compared to non-bleeding patients (17.8 IU/ml; range 1.0-157). No statistically significant differences in regard to median serum CA 125 levels between symptomatic and normal pregnancies occurred: normal pregnancy, 25.5 IU/ml (range 3.2-97); ectopic pregnancy, 26 IU/ml (range 1.3-157); missed abortion, 19.1IU/ml (range 1-242); threatened abortion, 48 IU/ml (range 5.2-540); spontaneous abortion, 40 IU/ml (range 5.4-442). Study 2: Initial CA 125 levels did not differ significantly between both groups of patients with 27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml. After 5-7 days, CA 125 in all patients who eventually aborted remained high or increased whereas non-aborters all had constantly low or steeply declining CA 125 measures. beta-hCG increased in all non-aborters but also in 13/18 aborters during the 5-7 day interval. Single serum measurements of CA 125 in symptomatic first trimester pregnant patients failed to discriminate spontaneous abortion, ectopic or normal pregnancies. However, sequential determinations of maternal CA 125 measurements appear to be a highly sensitive prognostic marker in patients with viable pregnancy at risk for abortion.

Glycosaminoglycan and transforming growth factor beta1 changes in human plasma and urine during the menstrual cycle, in vitro fertilization treatment, and pregnancy.

PubMed

De Muro, Pierina; Capobianco, Giampiero; Formato, Marilena; Lepedda, Antonio Junior; Cherchi, Gian Mario; Gordini, Laila; Dessole, Salvatore

2009-07-01

To evaluate transforming growth factor beta1 (TGF-beta1) and glycosaminoglycans (GAG) changes in human plasma and urine during the menstrual cycle, IVF-ET, and pregnancy. Prospective clinical study. University hospital. Thirteen women with apparently normal menstrual cycle (group 1); 18 women undergoing IVF-ET (group 2); and 14 low-risk pregnant women (group 3). We assayed plasma and urine concentrations of TGF-beta1, urine content, and distribution of GAG. Blood and urine samples were collected during days 2 to 3, 12 to 13, and 23 to 24 in group 1; in group 2, samples were obtained at menstrual phase, oocyte pick-up day, and 15 days after ET; in group 3, samples were obtained during gestational weeks 10-12, 22-24, and 30-32 and 1 month after delivery. Changes in TGF-beta1 and GAG content. The mean value of total urinary trypsin inhibitor/chondroitin sulfate (UTI/CS) showed a distinct peak at day 12 of the menstrual cycle in the fertile women in whom we monitored the ovulatory period. In the IVF-ET group, GAG distribution and TGF-beta1 levels showed significant differences during the cycle. We observed increased levels of plasma TGF-beta1 15 days after ET. A significant increase of total UTI/CS value with increasing gestation was detected. Transforming growth factor beta1 and GAG levels could represent an additional tool to monitor reproductive events and could be useful, noninvasive markers of ovulation and ongoing pregnancy.

Evaluation of the transforming growth factor-beta activity in normal and dry eye human tears by CCL-185 cell bioassay.

PubMed

Zheng, Xiaofen; De Paiva, Cintia S; Rao, Kavita; Li, De-Quan; Farley, William J; Stern, Michael; Pflugfelder, Stephen C

2010-09-01

To develop a new bioassay method using human lung epithelial cells (CCL-185) to assess activity of transforming growth factor beta (TGF-beta) in human tear fluid from normal subjects and patients with dry eye. Two epithelial cell lines, mink lung cells (CCL-64) and human lung cells (CCL-185), were compared to detect the active form of TGF-beta by BrdU incorporation (quantitation of cell DNA synthesis) and WST assay (metabolic activity of viable cells). The effect of TGF-beta on the growth of CCL-185 cells was observed microscopically. Human tears from normal control subjects and patients with dry eye (DE) with and without Sjögren syndrome were evaluated for TGF-beta concentration by Luminex microbead assay, and TGF-beta activity by the CCL-185 cell growth inhibition bioassay. The metabolic activity of viable CCL-185 cells, measured by WST, was shown to be proportional to the TGF-beta1 concentration (R = 0.919) and confirmed by BrdU assay (R = 0.969). Compared with CCL-185, metabolic activity of viable cells and DNA synthesis, measured by WST and BrdU incorporation assays, were shown to be less proportional to the TGF-beta1 concentration in the CCL-64 line (R = 0.42 and 0.17, respectively). Coincubation with human anti-TGF-beta1 antibody (MAB-240) yielded a dose-dependent inhibition of TGF-beta1 (0.3 ng/mL) activity. CCL-185 cell growth observed microscopically was noted to decrease in response to increasing TGF-beta1 concentrations. Levels of immuodetectable TGF-beta1 and TGF-beta2 were similar in normal and DE tears. TGF-beta bioactivity in DE human tears measured by the CCL-185 cells assay was found to be higher (9777.5 +/- 10481.9 pg/mL) than those in normal controls (4129.3 +/- 1342.9 pg/mL) (P < 0.05). Among patients with DE, TGF-beta bioactivity was highest in those with Sjögren syndrome. Approximately, 79.1% of TGF-beta in DE tears and 37.6% TGF-beta in normal tears were found to be biologically active. The CCL-185 cell assay was found to be a suitable tool for assessing TGF-beta activity in human tears. Tear TGF-beta bioactivity increases in DE, particularly in Sjögren syndrome, where elevated levels of TGF-beta1 transcripts in the conjunctival epithelium have been previously detected.

Beta-catenin is required for memory consolidation.

PubMed

Maguschak, Kimberly A; Ressler, Kerry J

2008-11-01

beta-catenin has been implicated in neuronal synapse regulation and remodeling. Here we have examined beta-catenin expression in the adult mouse brain and its role in amygdala-dependent learning and memory. We found alterations in beta-catenin mRNA and protein phosphorylation during fear-memory consolidation. Such alterations correlated with a change in the association of beta-catenin with cadherin. Pharmacologically, this consolidation was enhanced by lithium-mediated facilitation of beta-catenin. Genetically, the role of beta-catenin was confirmed with site-specific deletions of loxP-flanked Ctnnb1 (encoding beta-catenin) in the amygdala. Baseline locomotion, anxiety-related behaviors and acquisition or expression of conditioned fear were normal. However, amygdala-specific deletion of Ctnnb1 prevented the normal transfer of newly formed fear learning into long-term memory. Thus, beta-catenin may be required in the amygdala for the normal consolidation, but not acquisition, of fear memory. This suggests a general role for beta-catenin in the synaptic remodeling and stabilization underlying long-term memory in adults.

Setting limits on q0 from gravitational lensing

NASA Technical Reports Server (NTRS)

Gott, J. Richard, III; Park, Myeong-Gu; Lee, Hyung Mok

1989-01-01

Gravitational lensing by galaxies in a wide variety of cosmological models is considered. For closed models, the lensing depends on the parameter beta(crit). If beta(crit) is greater than zero, a normal lensing case can be obtained with two bright images separated by an angle twice beta(crit) and a third, arbitrarily dim image between them coincident with the position of the lensing galaxy nucleus. As the QSO approaches the antipodal redshift, which can occur in models with large values of the cosmological constant, the cross sections for lensing blow up. An overfocused case where beta(crit) is less than zero can be obtained for a QSO beyond the antipodal redshift. In this case, when a lensing event occurs, only one arbitrarily dim image coincident with the position of the lensing galaxy nucleus is seen. If galaxy rotation curves are always flat or slowly rising, the overfocused case always produces one image.

Inhibin/activin-betaC and -betaE subunits in the Ishikawa human endometrial adenocarcinoma cell line.

PubMed

Kimmich, Tanja; Brüning, Ansgar; Käufl, Stephanie D; Makovitzky, Josef; Kuhn, Christina; Jeschke, Udo; Friese, Klaus; Mylonas, Ioannis

2010-08-01

Inhibins and activins are important regulators of the female reproductive system. Recently, two novel inhibin subunits, named betaC and betaE, have been identified and shown to be expressed in several human tissues. However, only limited data on the expression of these novel inhibin subunits in normal human endometrial tissue and endometrial adenocarcinoma cell lines exist. Samples of proliferative and secretory human endometrium were obtained from five premenopausal, non-pregnant patients undergoing gynecological surgery for benign diseases. Normal endometrial tissue and Ishikawa endometrial adenocarcinoma cell lines were analyzed by immunohistochemistry, immunofluorescence and RT-PCR. Expression of the inhibin betaC and betaE subunits could be demonstrated at the protein level by means of immunohistochemical evaluation and at the transcriptional level by establishing a betaC- and betaE-specific RT-PCR analysis in normal human endometrial tissue and the parental Ishikawa cell line. Interestingly, in a highly de-differentiated subclone of the Ishikawa cell line lacking estrogen receptor expression, the expression of the inhibin-betaC subunit appeared strongly reduced. Here, we show for the first time that the novel inhibin/activin-betaC and -betaE subunits are expressed in normal human endometrium and the estrogen receptor positive human endometrial carcinoma cell line Ishikawa using RT-PCR and immunohistochemical detection methods. Interestingly, the Ishikawa minus cell line (lacking estrogen receptor expression) demonstrated no to minimal expression of the betaC subunit as observed with immunofluorescence and RT-PCR, suggesting a possible hormone- dependency of this subunit in human endometrial cancer cells. Moreover, because the Ishikawa cell line minus is thought to be a more malignant endometrial cell line than its estrogen receptor positive counterpart, inhibin-betaC subunit might be substantially involved in the pathogenesis and malignant transformation in human endometrium.

A comparison of heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major.

PubMed

Amoozgar, Hamid; Zeighami, Samaneh; Haghpanah, Sezaneh; Karimi, Mehran

2017-01-01

The goal of this study was to compare heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major. In this cross-sectional study, 60 patients with beta thalassemia major and 60 patients with beta thalassemia intermedia who had clinically no symptoms of arrhythmia and clinically normal heart function were evaluated using 24-hour ambulatory electrocardiogram monitoring and echocardiography. For data analysis SPSS ver.20 software was used. A P-value of less than 0.05 was considered statistically significant. The mean age of the beta thalassemia intermedia patients was 24.18 ± 7.9 years and the mean age in beta thalassemia major was 24.38 ± 7.7 years (P>0.05). Premature atrial contractions (PACs) were observed in 14 (23.3%) patients with beta thalassemia intermedia and in 22 (36.6%) beta thalassemia major patients. Premature ventricular contractions (PVCs) were detected in 8 (13.3%) patients in the beta thalassemia intermediate group and 16 (26.6) patients in the beta thalassemia major group, respectively. The left ventricular diastolic dimension, end-diastolic volume, and stroke volume were significantly higher in beta thalassemia intermedia group (P<0.05). Pulmonary acceleration time as an indicator of pulmonary pressure was lower in beta thalassemia intermedia group. Both atrial and ventricular arrhythmias were more common in the beta thalassemia major group. Higher end-diastolic volume and stroke volume were detected in the beta thalassemia intermedia group. Pulmonary acceleration time was lower in the beta thalassemia intermedia group, which can be an indicator of higher pulmonary pressure.

Management of hypertension in actively exercising patients. Implications for drug selection.

PubMed

Klaus, D

1989-02-01

In general, rises in systolic blood pressure to over 200 mm Hg during exercise with a workload of 100W are regarded as pathological. Excessive exercise blood pressure values are to be expected in principle in all hypertensives. However, there are so far no generally accepted criteria for diagnosis of isolated systolic exercise hypertension (with normal values of resting blood pressure). The incidence of isolated systolic exercise hypertension is estimated to be about 10% of a selected population. In patients with excessive rises in blood pressure during exercise who want to engage actively in sport, general measures (reduction of obesity, restriction of alcohol and salt intake) and endurance training should be recommended initially. For endurance training, sporting activities that involve dynamic exercise are to be recommended (walking, running, mountain hiking, cycling, swimming, cross-country skiing). Activities involving isometric exercise (rowing, diving, tennis) and sport of a competitive nature are not suitable. In moderately severe and severe hypertension (diastolic blood pressure values in excess of 105 mm Hg), sporting activities and endurance training are contraindicated. If the exercise blood pressure values cannot be lowered below 220 mm Hg with the general measures mentioned, pharmacotherapy is to be considered. The drugs of choice for suppressing excessive rises in blood pressure during exercise are beta-blockers. In this group, beta 1-blockers are to be preferred to non-selective beta-blockers because of the metabolic neutrality of the former. beta-Blockers without intrinsic sympathomimetic activity (ISA) lower the blood pressure-pulse rate product more effectively than beta-blockers with ISA. Alternatively, calcium antagonists of the verapamil type and ACE inhibitors can be employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Radioimmunoassay of tumor markers in serum of patients with renal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cordoni-Voutsas, M.; Glaubitt, D.; Wagner, W.

1984-01-01

Having noted an increased serum level of TPA and CEA in patients with renal carcinoma the authors extended these studies by using a larger number of tumor markers. In 15 patients (11 men and 4 women after menopause) aged 33 to 74 years who had renal carcinoma, among them 3 with tumor metastases, the serum concentration of TPA, CA 12-5, CEA, AFP, ferritin, prolactin, ..beta..-HCG, and ..beta../sub 2/-microglobulin was measured by radioimmunoassay. Monoclonal antibodies were used in the determination of serum CA 12-5 and CEA. In all patients surgical treatment, irradiation, or cytostatic therapy had not been performed. In serummore » the normal range was exceeded by TPA in 7 patients, CA 12-5 in 3, CEA and AFP in one each, ferritin in 12, prolactin in 2, and ..beta../sub 2/-microglobulin in 10 patients. In one man serum prolactin was reduced. Serum ..beta..-HCG was normal in all patients. According to these results serum ferritin, TPA, and ..beta../sub 2/-microglobulin are of great value as tumor markers in patients with renal carcinoma. In several patients the increase of serum ..beta../sub 2/-microglobulin may be ascribed partly to deterioration of renal function. As no consistent patterns of tumor markers in serum were observed it is recommended to determine several tumor markers and not only one of them during the follow-up of patients. Radioimmunoassays for measuring the serum level of tumor markers, especially ferritin, TPA, and ..beta../sub 2/-microglobulin, may considerably assist in the management of patients with renal carcinoma by providing early information about tumor recurrence or metastases.« less

Measuring the Accuracy of Simple Evolving Connectionist System with Varying Distance Formulas

NASA Astrophysics Data System (ADS)

Al-Khowarizmi; Sitompul, O. S.; Suherman; Nababan, E. B.

2017-12-01

Simple Evolving Connectionist System (SECoS) is a minimal implementation of Evolving Connectionist Systems (ECoS) in artificial neural networks. The three-layer network architecture of the SECoS could be built based on the given input. In this study, the activation value for the SECoS learning process, which is commonly calculated using normalized Hamming distance, is also calculated using normalized Manhattan distance and normalized Euclidean distance in order to compare the smallest error value and best learning rate obtained. The accuracy of measurement resulted by the three distance formulas are calculated using mean absolute percentage error. In the training phase with several parameters, such as sensitivity threshold, error threshold, first learning rate, and second learning rate, it was found that normalized Euclidean distance is more accurate than both normalized Hamming distance and normalized Manhattan distance. In the case of beta fibrinogen gene -455 G/A polymorphism patients used as training data, the highest mean absolute percentage error value is obtained with normalized Manhattan distance compared to normalized Euclidean distance and normalized Hamming distance. However, the differences are very small that it can be concluded that the three distance formulas used in SECoS do not have a significant effect on the accuracy of the training results.

Treatment with unsaponifiable extracts of avocado and soybean increases TGF-beta1 and TGF-beta2 levels in canine joint fluid.

PubMed

Altinel, Levent; Saritas, Z Kadir; Kose, Kamil Cagri; Pamuk, Kamuran; Aksoy, Yusuf; Serteser, Mustafa

2007-02-01

Avocado and soya unsaponifiables (ASU) are plant extracts used as a slow-acting antiarthritic agent. ASU stimulate the synthesis of matrix components by chondrocytes, probably by increasing the production of transforming growth factor-beta (TGF-beta). TGF-beta is expressed by chondrocytes and osteoblasts and is present in cartilage matrix. This study investigates the effect of ASU treatment on the levels of two isoforms of TGFbeta, TGF-beta1 and TGF-beta2, in the knee joint fluid using a canine model. Twenty-four outbred dogs were divided into three groups. The control animals were given a normal diet, while the treated animals were given 300 mg ASU every three days or every day. Joint fluid samples were obtained prior to treatment, and at the end of every month (up to three months). TGF-beta1 and TGF-beta2 levels were measured using a quantitative sandwich enzyme immunoassay technique. ASU treatment caused an increase in TGF-beta1 and TGF-beta2 levels in the joint fluid when compared to controls. The different doses did not cause a significant difference in joint fluid TGF levels. TGF-beta1 levels in the treated animals reached maximum values at the end of the second month and then decreased after the third month, while TGF-beta2 levels showed a marginal increase during the first two months, followed by a marked increase at the end of the third month. In conclusion, ASU increased both TGF-beta1 and TGF-beta2 levels in knee joint fluid.

Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate.

PubMed Central

Knox, J. D.; Cress, A. E.; Clark, V.; Manriquez, L.; Affinito, K. S.; Dalkin, B. L.; Nagle, R. B.

1994-01-01

The epithelial basal lamina composition and integrin expression profile of normal and neoplastic human prostate was characterized using immunohistochemical analysis of frozen samples. The major components of the basal lamina surrounding normal acini were laminin, type IV collagen, entactin, and type VII collagen with variable amounts of tenascin. The basal lamina of neoplastic acini had a similar composition, except for the loss of type VII collagen, which was observed in all grades of carcinoma. The basal cells of the normal prostate express the alpha 6-, beta 1-, and beta 4-integrin subunits, suggesting that both the alpha 6 beta 1- and alpha 6 beta 4-integrin complexes are formed. In prostate carcinoma there is a complete loss of beta 4 expression and the alpha 6- and beta 1-integrin subunits, which are restricted to the basal and basal lateral surfaces of basal cells, are distributed diffusely throughout the cytoplasmic membrane. The differential expression of type VII collagen and beta 4 are discussed in relationship to their possible role in tumor progression. Images Figure 1 Figure 2 Figure 3 PMID:8030747

Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.

PubMed

Kanasaki, Keizo; Kanda, Yoshiko; Palmsten, Kristin; Tanjore, Harikrishna; Lee, Soo Bong; Lebleu, Valerie S; Gattone, Vincent H; Kalluri, Raghu

2008-01-15

The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.

Gamow-Teller Strength for the Mixed Ground State of ARGON-35 via the (proton, Neutron) Reaction.

NASA Astrophysics Data System (ADS)

Wagner, Anthony James

1988-12-01

Early asymmetry measurements of the mixed beta-decay of the ground state of ^{35}Ar to the ground state of ^{35}Cl showed an "anomalous" value of G_{rm V}. This anomalous value surprisingly would infer that unitary symmetry, believed to be spontaneously broken in nature, has been restored in this singular case. From the definition of rho^2, this "anomalous" value also infers a "anomalous" value for B(GT)/B(F). When the half-life data is used instead without the results of the asymmetry experiment, one obtains a different ("normal") value of B(GT)/B(F). The quantity rho^2 derived from the early asymmetry experiments is considered suspect. It has recently been shown that the (p,n) reaction at intermediate energies provides a strong interaction probe of the identical B(GT)/B(F) nuclear strength ratio that can be measured in beta-decay. The value of G_{rm A}/G _{rm V} has been determined very accurately from the beta -decay of the neutron. Thus, (p,n) can be used to determine via a totally independent measurement the value of B(GT)/B(F). The global proportionality constant E _{rm O} = 55 +/- 0.4 MeV is used to analyze the results of a 160 MeV Polarimeter experiment to distinguish between the normal and anomalous value. The results showed more spin-flip probability than was expected. A 120 MeV cross section experiment was required to check whether there was additional spin-flip probability due to a non-negligible DeltaL = 2 component. The results showed a negligible DeltaL = 2 component. The specific proportionality ({ sigma}_{rm GT} (Ground State) = {sigma} _{rm GT} (Excited State)) was then used to reanalyze the results of both experiments. The results showed a B(GT)/B(F) = 0.058 +/- 0.007. The specific proportionality gave a global proportionality constant of E_{rm O} = 32.2 +/- 1.9 MeV. The reason for this deviation in E_{rm O} is not understood.

A re-examination of the metabolic equivalent concept in individuals with coronary heart disease.

PubMed

Savage, Patrick D; Toth, Michael J; Ades, Philip A

2007-01-01

The metabolic equivalent (MET) is a commonly used method of quantifying the energy cost and intensity of physical activity. Recent studies have questioned the accuracy of the well-accepted value of a MET of 3.5 mL O2.kg(-1).min(-1). The goal of the present study was to compare the traditionally accepted value for 1 MET to direct measures of resting metabolic rate in a group of stable individuals with coronary heart disease (CHD). The primary cohort consisted of 109 (60 men and 49 women) subjects with documented coronary heart disease and a body mass index >or=25 kg/m2. Measurements included indirect calorimetry, body composition, and exercise capacity (peak oxygen uptake [VO2]). In a substudy of 17 (10 men, 7 women) normal weight subjects (body mass index <25 kg/m2), metabolic rate in the seated position was also measured. Mean resting value for 1 MET was a VO2 value of 2.58 +/- 0.4 mL O2.kg(-1).min(-1) for overweight subjects measured in the supine position and 2.84 +/- 0.59 mL O2.kg(-1).min(-1) for normal weight individuals measured in the seated position. Caloric expenditure value was 0.74 +/- 0.12 kcal.kg(-1).h(-1) rather than the expected value of 1 kcal.kg(-1).h(-1). Values were similar between men and women. Women on beta-blockers had a lower resting metabolic rate (2.47 +/- 0.27 vs. 2.71 +/- 0.38 mL O2.kg(-1).min(-1)) (P < .05) than women not on beta-blocker therapy, whereas there was no effect of beta-blockers in men. Findings confirm recent studies of otherwise healthy individuals and indicate that the average resting metabolic rate in subjects with coronary heart disease is 23% to 36% lower than the widely accepted value of 3.5 mL O2.kg(-1).min(-1). Results demonstrate the limitation of the convention of expressing energy expenditure in multiples of an assumed constant.

Characterization and membrane organization of beta 1----3- and beta 1----4-galactosyltransferases from human colonic adenocarcinoma cell lines Colo 205 and SW403: basis for preferential synthesis of type 1 chain lacto-series carbohydrate structures.

PubMed

Holmes, E H

1989-05-01

Evidence indicates that activation of a beta 1----3N-acetylglucosaminyltransferase is responsible for accumulation of large quantities of lacto-series tumor-associated antigens in human colonic adenocarcinomas. Expression of type 1 and 2 core chain derivatives characterize human colonic adenocarcinomas, whereas normal adult colonic epithelial cells express detectable quantities of only type 1 chain derivatives. The basis for preferential synthesis of type 1 chain lacto-series carbohydrate structures characteristic of normal colonic mucosa and human colonic adenocarcinoma Colo 205 cells has been studied. The beta 1----3- and beta 1----4galactosyltransferase enzymes associated with synthesis of type 1 and 2 core chain structures, respectively, have been separated from a Triton X-100 solubilized membrane fraction of Colo 205 cells by chromatography on an alpha-lactalbumin-Sepharose column and their properties studied. Optimal transfer of beta 1----3-linked galactose to acceptor Lc3 occurred in the presence of 0.1% Triton CF-54 with Triton X-100 providing 75% of maximal activity. The enzyme was active over a broad pH range from 6.5 to 7.5 and had a near absolute requirement for Mn2+. The Km values for donor UDPgalactose and acceptor Lc3 were determined to be 48 and 13 microM, respectively. In contrast, the beta 1----4galactosyltransferase required taurodeoxycholate for maximal activity and the Km for Lc3 was found to be 20-fold higher than that for the beta 1----3-specific enzyme under the same assay conditions. Studies with membrane-bound beta 1----3- and beta 1----4galactosyltransferases as found in Golgi-rich membrane fractions of SW403 and Colo 205 adenocarcinoma cells showed that preferential synthesis of type 1 chain structures occurs under conditions similar to those in vivo for biosynthesis of lacto-series core chains. The results suggest that both the higher affinity of the beta 1----3galactosyltransferase for acceptor Lc3 and the membrane organizational features result in preferential synthesis of type 1 chain structures.

Insulin-producing cells could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells

PubMed Central

2013-01-01

Objective The aim of this study was to compare the difference between insulin-producing cells (IPCs) and normal human pancreatic beta cells both in physiological function and morphological features in cellular level. Methods The levels of insulin secretion were measured by enzyme-linked immunosorbent assay. The insulin gene expression was determined by real-time quantitative polymerase chain reaction. The morphological features were detected by atomic force microscopy (AFM) and laser confocal scanning microscopy. Results IPCs and normal human pancreatic beta cells were similar to each other under the observation in AFM with the porous structure features in the cytoplasm. Both number of membrane particle size and average roughness of normal human beta cells were higher than those of IPCs. Conclusions Our results firstly revealed that the cellular ultrastructure of IPCs was closer to that of normal human pancreatic beta cells, but they still could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells. PMID:23421382

Effects of fenoterol on ventilatory responses to hypoxia and hypercapnia in normal subjects.

PubMed Central

Yoshiike, Y.; Suzuki, S.; Watanuki, Y.; Okubo, T.

1995-01-01

BACKGROUND--The effects of beta 2 adrenergic agonists on chemoreceptors remain controversial. This study was designed to examine whether fenoterol, a beta 2 adrenergic agonist, increases the ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR) in normal subjects. METHODS--HCVR was tested with a rebreathing method and HVR was examined with a progressive isocapnic hypoxic method in 11 normal subjects. Both HCVR and HVR were assessed by the slope of occlusion pressure (P0.1) or ventilation (VE) plotted against end tidal carbon dioxide pressure and arterial oxygen saturation, respectively. Respiratory muscle strength, spirometric values and lung volume were measured. After a single oral administration of 5 mg fenoterol or placebo HCVR and HVR were evaluated. RESULTS--Fenoterol treatment did not change the specific airway conductance or forced expiratory volume in one second. Respiratory muscle strength did not change. Fenoterol increased the slope of the HCVR of both P0.1 (from 0.251 (0.116) to 0.386 (0.206) kPa/kPa, average increase 71%) and VE (from 10.7 (3.4) to 15.1 (4.2) l/min/kPa, average increase 52%), and shifted the response curves to higher values. For the HVR fenoterol increased the slopes of both P0.1 and VE (from -4.06 (2.00) x 10(-3) to -7.99 (4.29) x 10(-3) kPa/%, an average increase of 83%, and from -0.221 (0.070) to -0.313 (0.112) l/min/%, a 44.5% increase, respectively), and shifted the response curves to higher values. CONCLUSION--Acute administration of fenoterol increases the ventilatory responses to both hypercapnia and hypoxia in normal subjects. PMID:7701451

Expression of transforming growth factor-beta1, -beta2 and -beta3 in normal and diseased canine mitral valves.

PubMed

Aupperle, H; März, I; Thielebein, J; Schoon, H-A

2008-01-01

The pathogenesis of chronic valvular disease (CVD) in dogs remains unclear, but activation and proliferation of valvular stromal cells (VSC) and their transdifferentiation into myofibroblast-like cells has been described. These alterations may be influenced by transforming growth factor-beta (TGF-beta), a cytokine involved in extracellular matrix (ECM) regulation and mesenchymal cell differentiation. The present study investigates immunohistochemically the expression of TGF-beta1, -beta2, -beta3 and smooth muscle alpha actin (alpha-SMA) in normal canine mitral valves (MVs) (n=10) and in the valves of dogs with mild (n=7), moderate (n=14) and severe (n=9) CVD. In normal mitral valves there was no expression of alpha-SMA but VSC displayed variable expression of TGF-beta1 (10% of VSC labelled), TGF-beta2 (1-5% labelled) and TGF-beta3 (50% labelled). In mild CVD the affected atrialis contain activated and proliferating alpha-SMA-positive VSC, which strongly expressed TGF-beta1 and -beta3, but only 10% of these cells expressed TGF-beta2. In unaffected areas of the leaflet there was selective increase in expression of TGF-beta1 and -beta3. In advanced CVD the activated subendothelial VSC strongly expressed alpha-SMA, TGF-beta1 and -beta3. Inactive VSC within the centre of the nodules had much less labelling for TGF-beta1 and -beta3. TGF-beta1 labelling was strong within the ECM. These data suggest that TGF-beta plays a role in the pathogenesis of CVD by inducing myofibroblast-like differentiation of VSC and ECM secretion. Changed haemodynamic forces and expression of matrix metalloproteinases (MMPs) may in turn regulate TGF-beta expression.

Could aspiration of the Graafian follicle cause luteal phase deficiency?

PubMed

Feichtinger, W; Kemeter, P; Szalay, S; Beck, A; Janisch, H

1982-02-01

Luteal phase quality was evaluated in 32 patients wih nonstimulated cycles after laparoscopic oocyte recovery for in vitro fertilization. A luteal phase deficiency occurred in two cases (6.2%), the mean duration of the luteal phase was 13.5 +/- 1.3 days in 30 patients, and two patients developed amenorrhea of 23 and 43 days respectively after laparoscopy in spite of normal progesterone values 7 and 9 days after oocyte recovery. Six embryo transfers were performed after fertilization and regular cleavage of the obtained oocytes. No pregnancy resulted from the embryo transfers, although the patients had apparently normal luteal phases. In one patient there was a transient beta-subunit human chorionic gonadotropin (beta-hCG) elevation in serum. Luteal phase deficiency should not be main cause of a nonsuccessful embryo transfer. However, a prophylactic luteal phase support after oocyte recovery and embryo transfer in nonstimulated cycles is proposed.

Hb Valletta [beta87(F3)Thr-->Pro] and Hb Marseille/Long Island [beta2(NA2)His-->Pro; (-1)Met-(+1)Val-(+2)Pro-Leu], in a unique compound heterozygote with a normal hemoglobin phenotype.

PubMed

Galdies, Ruth; Cassar, Wilhelmina; Pizzuto, Monica; Scerri, Christian A; Felice, Nicholas; Cassar, Olivianne A; Buttigieg, George; Felice, Alex E

2010-01-01

This study refers to the quantitative hemoglobin (Hb) phenotype of a 19-year-old female with Hb Valletta [beta87(F3)Thr-->Pro] in association with Hb Marseille/Long Island [beta2(NA2)His-->Pro; (-1)Met-(+1)Val-(+2)Pro-Leu] and a normal Hb electrophoretogram. The data serve to alert investigators to the possibility that relatives with apparently normal Hb phenotypes may be transmitting mutant alleles and suggest methods for identification.

[Beta-endorphin and obesity. Possible pathogenetic implications].

PubMed

Giugliano, D; Saccomanno, F; Quatraro, A; Ceriello, A; Torella, R

1990-01-01

Several experimental data have documented the ability of both opiates and opioid peptides to stimulate food intake. On the other hand, the plasma beta-endorphin levels found in obese patients are higher than those observed in normal-weight controls, which may have pathogenetic implications. We have investigated the responses of plasma glucose, insulin, C-peptide and glucagon to an infusion of human beta-endorphin in formerly obese subjects who had obtained by dieting the normalization of body weight and in lean controls. The data show that: a) the increased plasma beta-endorphin concentrations found in human obesity are not corrected by normalization of body weight; b) formerly obese subjects behave as obese subjects in their metabolic and hormonal responses to beta-endorphin.

Inhibition of beta-adrenergic receptor trafficking in adult cardiocytes by MAP4 decoration of microtubules.

PubMed

Cheng, Guangmao; Qiao, Fei; Gallien, Thomas N; Kuppuswamy, Dhandapani; Cooper, George

2005-03-01

Decreased beta-adrenergic receptor (beta-AR) number occurs both in animal models of cardiac hypertrophy and failure and in patients. beta-AR recycling is an important mechanism for the beta-AR resensitization that maintains a normal complement of cell surface beta-ARs. We have shown that 1) in severe pressure overload cardiac hypertrophy, there is extensive microtubule-associated protein 4 (MAP4) decoration of a dense microtubule network; and 2) MAP4 microtubule decoration inhibits muscarinic acetylcholine receptor recycling in neuroblastoma cells. We asked here whether MAP4 microtubule decoration inhibits beta-AR recycling in adult cardiocytes. [(3)H]CGP-12177 was used as a beta-AR ligand, and feline cardiocytes were isolated and infected with adenovirus containing MAP4 (AdMAP4) or beta-galactosidase (Adbeta-gal) cDNA. MAP4 decorated the microtubules extensively only in AdMAP4 cardiocytes. beta-AR agonist exposure reduced cell surface beta-AR number comparably in AdMAP4 and Adbeta-gal cardiocytes; however, after agonist withdrawal, the cell surface beta-AR number recovered to 78.4 +/- 2.9% of the pretreatment value in Adbeta-gal cardiocytes but only to 56.8 +/- 1.4% in AdMAP4 cardiocytes (P < 0.01). This result was confirmed in cardiocytes isolated from transgenic mice having cardiac-restricted MAP4 overexpression. In functional terms of cAMP generation, beta-AR agonist responsiveness of AdMAP4 cells was 47% less than that of Adbeta-gal cells. We conclude that MAP4 microtubule decoration interferes with beta-AR recycling and that this may be one mechanism for beta-AR downregulation in heart failure.

Recalibrated Equations for Determining Effect of Oil Filtration on Rolling Bearing Life

NASA Technical Reports Server (NTRS)

Needelman, William M.; Zaretsky, Erwin V.

2014-01-01

In 1991, Needelman and Zaretsky presented a set of empirically derived equations for bearing fatigue life (adjustment) factors (LFs) as a function of oil filter ratings. These equations for life factors were incorporated into the reference book, "STLE Life Factors for Rolling Bearings." These equations were normalized (LF = 1) to a 10-micrometer filter rating at Beta(sub x) = 200 (normal cleanliness) as it was then defined. Over the past 20 years, these life factors based on oil filtration have been used in conjunction with ANSI/ABMA standards and bearing computer codes to predict rolling bearing life. Also, additional experimental studies have been made by other investigators into the relationship between rolling bearing life and the size, number, and type of particle contamination. During this time period filter ratings have also been revised and improved, and they now use particle counting calibrated to a new National Institute of Standards and Technology (NIST) reference material, NIST SRM 2806, 1997. This paper reviews the relevant bearing life studies and describes the new filter ratings. New filter ratings, Beta(sub x(c)) = 200 and Beta(sub x(c)) = 1000, are benchmarked to old filter ratings, Beta(sub x) = 200, and vice versa. Two separate sets of filter LF values were derived based on the new filter ratings for roller bearings and ball bearings, respectively. Filter LFs can be calculated for the new filter ratings.

Transduction of beta3 integrin subunit cDNA confers on human keratinocytes the ability to adhere to gelatin.

PubMed

Kubo, Miyoko; Clark, Richard A F; Katz, Anne B; Taichman, Lorne B; Jin, Zaishun; Zhao, Ying; Moriguchi, Takahiko

2007-04-01

alphavbeta3 is a multiligand integrin receptor that interacts with fibrinogen (FG), fibrin (FB), fibronectin (FN), vitronectin (VN), and denatured collagen. We previously reported that cultured normal human keratinocytes, like in vivo keratinocytes, do not express alphavbeta3 on the cell surface, and do not adhere to and migrate on FG and FB. Furthermore, we reported that human keratinocytes transduced with beta3 integrin subunit cDNA by a retrovirus-mediated transduction method express alphavbeta3 on the cell surface and adhere to FG, FB, FN, and VN significantly compared with beta-galactosidase (beta-gal) cDNA-transduced keratinocytes (control). In this study, we determined whether these beta3 integrin subunit cDNA-transduced keratinocytes or normal human keratinocytes adhere to denatured collagen (gelatin) using a 1 h cell adhesion assay. beta3 cDNA-transduced keratinocytes adhered to gelatin, whereas no significant adhesion was observed with the control cells (beta-gal cDNA-transduced keratinocytes and normal human keratinocytes). The adhesion to gelatin was inhibited by LM609, a monoclonal antibody to alphavbeta3, and RGD peptides but not by normal mouse IgG1 nor RGE peptides. Thus, transduction of beta3 integrin subunit cDNA confers on human keratinocytes the ability to adhere to denatured collagen (gelatin) as well as to FG, FB, VN, and FN. Otherwise, normal human keratinocytes do not adhere to gelatin. These data support the idea that beta3 cDNA-transduced human keratinocytes can be a good material for cultured epithelium to achieve better take rate with acute or chronic wounds, in which FG, FB, and denatured collagen are abundantly present.

Determination of the Accommodation Coefficient Using Vapor/gas Bubble Dynamics in an Acoustic Field

NASA Technical Reports Server (NTRS)

Gumerov, Nail A.; Hsiao, Chao-Tsung; Goumilevski, Alexei G.; Allen, Jeff (Technical Monitor)

2001-01-01

Nonequilibrium liquid/vapor phase transformations can occur in superheated or subcooled liquids in fast processes such as in evaporation in a vacuum. The rate at which such a phase transformation occurs depends on the "condensation" or "accommodation" coefficient, Beta, which is a property of the interface. Existing measurement techniques for Beta are complex and expensive. The development of a relatively inexpensive and reliable technique for measurement of Beta for a wide range of substances and temperatures is of great practical importance. The dynamics of a bubble in an acoustic field strongly depends on the value of Beta. It is known that near the saturation temperature, small vapor bubbles grow under the action of an acoustic field due to "rectified heat transfer." This finding can be used as the basis for an effective measurement technique of Beta. We developed a theory of vapor bubble behavior in an isotropic acoustic wave and in a plane standing acoustic wave. A numerical code was developed which enables simulation of a variety of experimental situations and accurately takes into account slowly evolving temperature. A parametric study showed that the measurement of Beta can be made over a broad range of frequencies and bubble sizes. We found several interesting regimes and conditions which can be efficiently used for measurements of Beta. Measurements of Beta can be performed in both reduced and normal gravity environments.

[Investigation of adolescents' bone metabolism in the western part of Transdanubia].

PubMed

Csákváry, Violetta; Puskás, Tamás; Bödecs, Tamás; Lôcsei, Zoltán; Oroszlán, György; Kovács, L Gábor; Toldy, Erzsébet

2009-10-25

Childhood reference range based on the age is not available in Hungary, therefore the diagnosis and therapy of bone metabolic diseases of childhood are subject to difficulties. The aim of this work is to provide information about the adolescents' results of bone mineral density and bone biomarkers. Measurements were performed in 169 healthy adolescents (98 girls, 71 boys, age: 17.0+/-1.2 years). Bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine were measured using Double X-ray Absorptiometry (DXA, LUNAR, GE Health Care, USA) and Z-score values were analyzed using different reference population. In the serum, bone biomarkers osteocalcin (OC) and beta-crosslaps (beta-Cl) were measured by a fully automated, electrochemiluminescence immunoassay method (Elecsys-2010, Roche). Data were analyzed according to gender and the Tanner stage and grade system. Associations between body mass index (BMI), calcium intake, consumption of soft drinks and coke, and physical exercise were investigated. BMC values for both age groups were significantly elevated in boys of the Tanner stage V. (15-16 years: 62.9+/-14.3 g; 17-19 years: 69.8+/-9.3g) than in girls (58.1+/-10.4; 61.6+/-8.5 g) (p<0.001). BMD values were higher in girls, than in boys (1.17+/-0.12 g/cm 2 vs. 1.13+/-0.11 g/cm 2) (p<0.05). OC and beta-Cl levels showed negative correlation with age in both gender (p<0.01), while OC and beta-Cl levels were higher in boys, than in girls (p<0.001). Elevation of BMC and BMD values were associated with increase of BMI in both gender (p<0.05), but the biomarkers in thin girls were higher, than in overweight girls (p<0.05). Authors obtained excellent correlations between the BMD-Z-score values compared to the German standard and to their own population (girls: r=0.97, boys: 0.88), but the absolute values significantly differed from one another. 80% of adolescents are on a diet with insufficient calcium intake, while 38% of them do not play sport regularly. Excessive intake of soft drinks was determined in 60% of adolescents. In the case of insufficient calcium intake (4.7%, 6/127), low bone mass was measured using the Z-score of the German reference values. Among children with adequate calcium intake, BMD assessed by DXA was normal. These data help to determine normal reference values among healthy high school students. Further studies are needed in wider range of young population for the establishment of Hungarian reference values of bone markers.

[Expression of EP-CAM, beta-catenin in the carcinogenesis of squamous cell carcinoma of uterine cervix].

PubMed

Yang, Jian-zhu; Zhang, Xiang-hong; Wu, Wen-xin; Yan, Xia; Liu, Yan-li; Wang, Jun-ling; Wang, Feng-rong

2003-07-01

To study the expression of EP-CAM, beta-catenin in the carcinogenesis of squamous cell carcinoma of uterine cervix. The expressions of EP-CAM and beta-catenin were detected with immunohistochemical stain in 14 cases of normal cervical squamous epithelium, 32 cases of cervical intraepithelial neoplasia (CIN) and 38 cases of cervical invasive squamous cell carcinoma. The over-expression rates of EP-CAM were 0, 7.1%, 20.0%, 62.5% and 55.3% for normal cervical epithelium, CINI, CINII, CINIII and carcinoma groups. The EP-CAM over-expression rates in CINIII and cervical carcinoma groups were significantly higher than those in normal epithelium and CINI groups (P < 0.001). No aberrant expression of beta-catenin was shown in normal cervical epithelium, while the aberrant expression rates of beta-catenin in CINI, CINII, CINIII and cervical carcinoma group were 28.6%, 40.0%, 62.5% and 84.2%. The aberrant expression rate of beta-catenin increased with the increase in degree of CIN and development of cervical carcinoma. The over-expression rate of EP-CAM was reversely related to the differentiation of cervical squamous cell carcinoma (P < 0.001). EP-CAM and beta-catenin may be involved in the carcinogenesis of squamous cell carcinoma of uterine cervix. The over-expression of EP-CAM and aberrant expression of beta-catenin may serve as markers of squamous carcinogenesis of uterine cervix.

Fibrinogen variant B[beta]D432A has normal polymerization but does not bind knob 'B'

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowley, Sheryl R.; Lord, Susan T.; UNC)

2009-10-23

Fibrinogen residue B{beta}432Asp is part of hole 'b' that interacts with knob 'B,' whose sequence starts with Gly-His-Arg-Pro-amide (GHRP). Because previous studies showed B{beta}D432A has normal polymerization, we hypothesized that B{beta}432Asp is not critical for knob 'B' binding and that new knob-hole interactions would compensate for the loss of this Asp residue. To test this hypothesis, we solved the crystal structure of fragment D from B{beta}D432A. Surprisingly, the structure (rfD-B{beta}D432A+GH) showed the peptide GHRP was not bound to hole 'b.' We then re-evaluated the polymerization of this variant by examining clot turbidity, clot structure, and the rate of FXIIIa cross-linking.more » The turbidity and the rate of - dimer formation for B{beta}D432A were indistinguishable compared with normal fibrinogen. Scanning electron microscopy showed no significant differences between the clots of B{beta}D432A and normal, but the thrombin-derived clots had thicker fibers than clots obtained from batroxobin, suggesting that cleavage of FpB is more important than 'B:b' interactions. We conclude that hole 'b' and 'B:b' knob-hole binding per se have no influence on fibrin polymerization.« less

Dissociation between cardiomyocyte function and remodeling with beta-adrenergic receptor blockade in isolated canine mitral regurgitation.

PubMed

Pat, Betty; Killingsworth, Cheryl; Denney, Thomas; Zheng, Junying; Powell, Pamela; Tillson, Michael; Dillon, A Ray; Dell'Italia, Louis J

2008-12-01

The low-pressure volume overload of isolated mitral regurgitation (MR) is associated with increased adrenergic drive, left ventricular (LV) dilatation, and loss of interstitial collagen. We tested the hypothesis that beta1-adrenergic receptor blockade (beta1-RB) would attenuate LV remodeling after 4 mo of MR in the dog. beta1-RB did not attenuate collagen loss or the increase in LV mass in MR dogs. Using MRI and three-dimensional (3-D) analysis, there was a 70% increase in the LV end-diastolic (LVED) volume-to-LV mass ratio, a 23% decrease in LVED midwall circumferential curvature, and a >50% increase in LVED 3-D radius/wall thickness in MR dogs that was not attenuated by beta1-RB. However, beta1-RB caused a significant increase in LVED length from the base to apex compared with untreated MR dogs. This was associated with an increase in isolated cardiomyocyte length (171+/-5 microm, P<0.05) compared with normal (156+/-3 microm) and MR (165+/-4 microm) dogs. Isolated cardiomyocyte fractional shortening was significantly depressed in MR dogs compared with normal dogs (3.73+/-0.31 vs. 5.02+/-0.26%, P<0.05) and normalized with beta1-RB (4.73+/-0.48%). In addition, stimulation with the beta-adrenergic receptor agonist isoproterenol (25 nM) increased cardiomyocyte fractional shortening by 215% (P<0.05) in beta1-RB dogs compared with normal (56%) and MR (50%) dogs. In summary, beta1-RB improved LV cardiomyocyte function and beta-adrenergic receptor responsiveness despite further cell elongation. The failure to attenuate LV remodeling associated with MR could be due to a failure to improve ultrastructural changes in extracellular matrix organization.

Noninvasive prediction of shunt operation outcome in idiopathic normal pressure hydrocephalus

PubMed Central

Aoki, Yasunori; Kazui, Hiroaki; Tanaka, Toshihisa; Ishii, Ryouhei; Wada, Tamiki; Ikeda, Shunichiro; Hata, Masahiro; Canuet, Leonides; Katsimichas, Themistoklis; Musha, Toshimitsu; Matsuzaki, Haruyasu; Imajo, Kaoru; Kanemoto, Hideki; Yoshida, Tetsuhiko; Nomura, Keiko; Yoshiyama, Kenji; Iwase, Masao; Takeda, Masatoshi

2015-01-01

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, cognitive deterioration and urinary incontinence in elderly individuals. These symptoms can be improved by shunt operation in some but not all patients. Therefore, discovering predictive factors for the surgical outcome is of great clinical importance. We used normalized power variance (NPV) of electroencephalography (EEG) waves, a sensitive measure of the instability of cortical electrical activity, and found significantly higher NPV in beta frequency band at the right fronto-temporo-occipital electrodes (Fp2, T4 and O2) in shunt responders compared to non-responders. By utilizing these differences, we were able to correctly identify responders and non-responders to shunt operation with a positive predictive value of 80% and a negative predictive value of 88%. Our findings indicate that NPV can be useful in noninvasively predicting the clinical outcome of shunt operation in patients with iNPH. PMID:25585705

Structural relationships between human erythrocyte sialoglycoproteins beta and gamma and abnormal sialoglycoproteins found in certain rare human erythrocyte variants lacking the Gerbich blood-group antigen(s).

PubMed Central

Reid, M E; Anstee, D J; Tanner, M J; Ridgwell, K; Nurse, G T

1987-01-01

The human erythrocyte membrane sialoglycoproteins beta and gamma are important for the maintenance of the discoid shape of the normal erythrocyte. In this paper we show that the human erythrocyte sialoglycoproteins beta and gamma (hereafter called beta and gamma) are structurally related. Rabbit antisera produced against purified beta and beta 1 and rendered specific to the cytoplasmic portion of these proteins also react with the cytoplasmic portion of gamma. Some human anti-Gerbich (Ge) sera react with the extracellular portion of both beta and gamma. This reactivity is shown to be directed towards a common epitope on beta and gamma. However, most anti-Ge sera do not react with beta, but react with an extracellular epitope only present on gamma. All individuals who lack the Ge antigens lack beta and gamma. In some cases abnormal sialoglycoproteins are present in the erythrocytes, and these are shown to be structurally related to beta and gamma. Rabbit antisera raised against the purified abnormal sialoglycoprotein from a Ge-negative erythrocyte type reacted with the cytoplasmic portion of both beta and gamma. Unlike normal beta and gamma, the abnormal sialoglycoproteins found in Ge-negative erythrocytes migrate as a diffuse band on SDS/polyacrylamide-gel electrophoresis. Studies using endoglycosidases suggest that the diffuse nature of these bands results from carbohydrate heterogeneity and that the abnormal sialoglycoproteins contain N-glycosidically linked oligosaccharides with repeating lactosamine units. Such polylactosamine chains are not present on normal beta or gamma. Images Fig. 1. Fig. 2. Fig. 3. PMID:2444210

Specific radioimmunoassay of human. beta. -endorphin in unextracted plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiedemann, E.; Saito, T.; Linfoot, J.A.

1979-09-01

With an antiserum against human ..beta..-endorphin (..beta..-EP) crossreacting <2% with human ..beta..-lipotropin (..beta..-LPH) by weight we have developed a radioimmunoassay that can detect 1 pg ..beta..-EP in diluted raw plasma. In a.m. fasting plasma of 14 normal subjects ..beta..-EP ranged from <5 to 45 pg/ml. ..beta..-EP was elevated in untreated, but normal in successfully treated Cushing's disease; undetectable in a patient with adrenal adenoma; extremely high in Nelson's syndrome; and elevated in a patient with bronchogenic carcinoma before, but undetectable after tumor resection. In subjects with intact hypothalamic-pituitary-adrenal axis, ..beta..-EP was undectectable after dexamethasone and increased after metyrapone administration andmore » insulin-induced hypoglycemia. ..beta..-EP concentration was considerably lower in serum than in simultaneously collected plasma, but increased in serum left unfrozen for several hours after clot removal. Thus, ..beta..-EP behaves like a hormone responding to the same stimuli as ACTH and ..beta..-LPH and blood appears to contain enzymes both generating and destroying immunoreactive ..beta..-EP.« less

[Relationship between the expression of beta-cat, cyclin D1 and c-myc and the occurance and biological behavior of pancreatic cancer].

PubMed

Li, Yu-jun; Ji, Xiang-rui

2003-06-01

To study the relationship between the abnormal expression of beta-catenin (beta-cat) and the high expressions of cyclin D1 and c-myc and the occurance, proliferation, infiltration, metastasis and prognosis of pancreatic cancer, and to provide rational basis for the clinical diagnosis and treatment. Immunohistochemical PicTure trade mark was used to examine the expressions of beta-cat, cyclin D1 and c-myc in 47 cases of the cancerous tissue of pancreas, 12 cases of the pancreatic intraepithelial neoplasia and 10 cases of normal tissue of pancreas, respectively. Pancreatic cancer proliferation cell nuclear antigen (PCNA) was also tested as the index of the extent of proliferation of the pancreatic cancer. beta-cat was expressed normally in the 10 cases of the normal pancreatic tissue, while cyclin D1 and c-myc were negative. The expression rates of beta-cat, cyclin D1 and c-myc in the tissues of the pancreatic intraepithelial neoplasia and the pancreatic cancer had no significant difference [6/12 and 68.1% (32/47), 6/12 and 74.5% (35/47), 5/12 and 70.2% (33/47) respectively;P values were all more than 0.05]. The abnormal expression rate of beta-cat was significantly correlated to the metastasis of the pancreatic cancer and the one-year survival rate (both P < 0.05), but had no relation with the size, the extent of differentiation, the activity of proliferation, or infiltration of the pancreatic cancer (both P > 0.05). The expression rate of cyclin D1 was correlated with the proliferation of the pancreatic cancer and the extent of differentiation (both P < 0.05), but not with the size, infiltration, metastasis, or one-year survival rate of the pancreatic cancer (both P > 0.05). The expression rate of c-myc was not correlated with the size, the extent of proliferation, infiltration, metastasis, or one-year survival rate (both P > 0.05), but closely with the proliferation activity of the cancerous tissue of pancreas (P < 0.05). The abnormal expression of beta-cat and the high expressions of cyclin D1 and c-myc had a parallel relationship with the pancreatic intraepithelial neoplasia and pancreatic cancer (both P < 0.05, gamma = 1.000, 0.845, 0.437, 0.452). The abnormal expression of beta-cat activates cyclin D1 and c-myc, and results in the unchecked proliferation and differentiation, which may play an important role in the genesis of the pancreatic cancer. The abnormal expression of beta-cat is one of the mechanisms for the spread of pancreatic cancer and an index in the molecular biology to determine the metastasis and prognosis of pancreatic cancer.

Universal binding energy relations in metallic adhesion

NASA Technical Reports Server (NTRS)

Ferrante, J.; Smith, J. R.; Rose, J. H.

1981-01-01

Scaling relations which map metallic adhesive binding energy onto a single universal binding energy curve are discussed in relation to adhesion, friction, and wear in metals. The scaling involved normalizing the energy to the maximum binding energy and normalizing distances by a suitable combination of Thomas-Fermi screening lengths. The universal curve was found to be accurately represented by E*(A*)= -(1+beta A) exp (-Beta A*) where E* is the normalized binding energy, A* is the normalized separation, and beta is the normalized decay constant. The calculated cohesive energies of potassium, barium, copper, molybdenum, and samarium were also found to scale by similar relations, suggesting that the universal relation may be more general than for the simple free electron metals.

Expression of beta-dystroglycan is reduced or absent in many human carcinomas.

PubMed

Cross, S S; Lippitt, J; Mitchell, A; Hollingsbury, F; Balasubramanian, S P; Reed, M W R; Eaton, C; Catto, J W; Hamdy, F; Winder, S J

2008-11-01

Dystroglycan is an important structural and signalling protein that is expressed in most human cells. alpha-Dystroglycan has been investigated and found to be reduced in human cancers, but there is only one published study on the expression of beta-dystroglycan in human cancer and that was only on small numbers of breast and prostatic cancers. The aim was to conduct a comprehensive immunohistochemical survey of the expression of beta-dystroglycan in normal human tissues and common cancers. Triplicate tissue microarrays of 681 samples of normal human tissues and common cancers were stained using an antibody directed against the cytoplasmic component of beta-dystroglycan. beta-Dystroglycan was strongly expressed at the intercellular junctions and basement membranes of all normal human epithelia. Expression of beta-dystroglycan was absent or markedly reduced in 100% of oesophageal adenocarcinomas, 97% of colonic cancers, 100% of transitional cell carcinomas of the urothelium and 94% of breast cancers. In the breast cancers, the only tumours that showed any retention of beta-dystroglycan expression were small low-grade oestrogen receptor-positive tumours. The only cancers that showed retention of beta-dystroglycan expression were cutaneous basal cell carcinomas. There is loss or marked reduction of beta-dystroglycan expression (by immunohistochemistry) in the vast majority of human cancers surveyed. Since beta-dystroglycan is postulated to have a tumour suppressor effect, this loss may have important functional significance.

Fabry disease: multidisciplinary evaluation after 10 years of treatment with agalsidase Beta.

PubMed

Juan, Politei; Hernan, Amartino; Beatriz, Schenone Andrea; Gustavo, Cabrera; Antonio, Michref; Eduardo, Tanus; Raul, Dominguez; Margarita, Larralde; Mariana, Blanco; Daniela, Gaggioli; Marina, Szlago

2014-01-01

Fabry disease is an X linked disorder of metabolism due to deficient α-galactosidase A activity. Enzyme replacement therapy (ERT) with agalsidase Beta was approved by EMA in 2001 and FDA in 2003. Six patients were enrolled. Baseline data was measured for renal, cardiac, and cerebrovascular functioning. We compared baseline quality of life scales with the current results. These parameters were assessed during the 10 years of follow-up period. Before ERT four patients showed normal eGFR, one stage 2 of CKD, and one hyperfiltration stage. All presented microalbuminuria and just two cases showed proteinuria. After 10 years of ERT, no patient showed decrease in renal functioning. One patient decreased from proteinuria to microalbuminuria range. Before treatment one case showed left ventricular (LV) hypertrophy and LV Mass Index was abnormal in two female patients. After 10 years echocardiographic values did not present progression to LVH and one female showed regression to normal values of LV posterior wall and interventricular septum. Brain MRI showed ischemic lesions in one female and vertebrobasilar dolichoectasia in one male. From baseline and during the follow-up period MRI did not progress to new ischemic lesions and there were no clinical signs of cerebrovascular damage. After 10 years quality of life showed improvement in all domains measured. Early treatment of agalsidase Beta is related to a better outcome regarding stability and regression of signs and symptoms in Fabry disease. Our results in patients with mild organ involvement showed good outcomes and support an early and continuous ERT.

Anisotropic shock jump conditions: Theory and observations

NASA Technical Reports Server (NTRS)

Chao, J. K.; Zhang, X. X.; Song, P.

1995-01-01

The MHD Rankine-Hugoniot (RH) relations for shock waves in a collisionless plasma with bi-Maxwellian distribution functions are considered. While by introducing the pressure anisotropy parameter xi in the RH relations, the number of unknowns -- B, V, n, p and xi (a total of 9) -- becomes one more than the total number of the conservation equations, it is possible to use the observed quantities on both sides of the shock to study the anisotropy changes across the shock. A simple relation for the anisotropy change across the shock is derived as a function of the ratio of magnetic fields m(= B'/B), the shock normal angle theta(sub Bn) and the plasma beta and beta' (primes are downstream values). Since m and theta(sub Bn) can be determined accurately in observation, the reliability of the anisotropy change deduced is mostly dependent on the accuracy of the measurements beta and beta'. We have applied the results to six low-beta quasi-perpendicular (Q perpendicular) laminar bow shock crossings with temperature anisotropy measured in the magnetosheath. In the six test cases, it is found that the predicted pressure anisotropies agree well with those observed in the magnetosheath.

Acid-base balance and cardiac index in SO2-bronchitic, papaine-emphysematous and paraquat-fibrotic rats after isoproterenol treatment.

PubMed

Vértes, K; Debreczeni, L A

1990-01-01

SO2-bronchitis, papaine-emphysema and paraquat fibrosis were induced in Wistar rats. Blood pressure, cardiac index, total peripheral resistance, arterial blood gas values, parameters of acid-base balance were determined. Effects of 0.1 and 0.3 microgram.-1.min-1 isoproterenol iv. infusion were examined. Morphologic alterations of the lungs were verified by histopathological examinations. All the parameters investigated were found to be normal in the control rats. The treated groups differed from the normal ones: an increased blood pressure was observed in emphysema and fibrosis. A decreased cardiac index was characteristic of chronic bronchitis, high cardiac index of emphysema, high TPR of bronchitis and arterial hypoxaemy of fibrosis. The groups reacted differently to beta adrenergic stimulation: in bronchitic and fibrotic rats the cardiac index was augmented, whereas in emphysematous ones the increase proved to be smaller. The effects of isoproterenol infusion can be related to the altered beta-receptor function in the various experimental pulmonary diseases.

Dysfunctional C8 beta chain in patients with C8 deficiency.

PubMed

Tschopp, J; Penea, F; Schifferli, J; Späth, P

1986-12-01

Two sera from unrelated individuals, each lacking C8 activity, were examined by Western blot analysis. Using antisera raised against whole C8, the two sera are shown to lack the C8 beta chain, indicating a C8 beta deficiency, which is frequently observed in cases of dysfunctional C8. In contrast, by means of a specific anti-C8-beta antiserum, a C8 beta-like polypeptide chain of apparently identical molecular weight compared to normal C8 beta was detected. Digestion of normal and dysfunctional C8 beta with Staphylococcus aureus V8 protease revealed distinct differences in the enzymatic digestion pattern. We conclude that the dysfunction in the C8 protein in these two patients resides in the dysfunctional C8 beta chain, and that this form of C8 deficiency is distinct from C8 deficiencies previously reported, in which one or both C8 subunits are lacking.

Basal Ganglia Beta Oscillations Accompany Cue Utilization

PubMed Central

Leventhal, Daniel K.; Gage, Gregory J.; Schmidt, Robert; Pettibone, Jeffrey R.; Case, Alaina C.; Berke, Joshua D.

2012-01-01

SUMMARY Beta oscillations in cortical-basal ganglia (BG) circuits have been implicated in normal movement suppression and motor impairment in Parkinson’s disease. To dissect the functional correlates of these rhythms we compared neural activity during four distinct variants of a cued choice task in rats. Brief beta (~20 Hz) oscillations occurred simultaneously throughout the cortical-BG network, both spontaneously and at precise moments of task performance. Beta phase was rapidly reset in response to salient cues, yet increases in beta power were not rigidly linked to cues, movements, or movement suppression. Rather, beta power was enhanced after cues were used to determine motor output. We suggest that beta oscillations reflect a postdecision stabilized state of cortical-BG networks, which normally reduces interference from alternative potential actions. The abnormally strong beta seen in Parkinson’s Disease may reflect overstabilization of these networks, producing pathological persistence of the current motor state. PMID:22325204

Inflammatory Cytokine Pattern Is Sex-Dependent in Mouse Cutaneous Melanoma Experimental Model

PubMed Central

Surcel, Mihaela

2017-01-01

We present the evaluation of inflammatory cytokines in mouse cutaneous melanoma experimental model, as markers of disease evolution. Moreover, to test our experimental model, we have used low doses of dacarbazine (DTIC). C57 BL/6J mouse of both sexes were subjected to experimental cutaneous melanoma and treated with low doses of DTIC. Clinical parameters and serum cytokines were followed during tumor evolution and during DTIC therapy. Cytokine/chemokine pattern was assessed using xMAP technology and the following molecules were quantified: interleukins (IL)-1-beta, IL-6, IL-10, IL-12 (p70), interferon (IFN)-gamma, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, monocyte chemoattractant protein (MCP-1), and keratinocyte-derived chemokine (KC). Significant differences were found between normal females and males mice, female mice having a statistically higher serum concentration of IL-1-beta compared to male mice, while males have a significantly higher concentration of MIP-1-alpha. During melanoma evolution in the female group, IL-1-beta, MIP-1-alpha, and KC circulatory levels were found 10-fold increased, while other cytokines doubled their values. In the male mice group, only circulatory KC increased 4 times, while IL-1-beta and TNF-alpha doubled their circulatory values. Various serum cytokines correlated with the disease evolution in cutaneous melanoma mouse model. PMID:29318162

Physics Basis for the Advanced Tokamak Fusion Power Plant ARIES-AT

DOE Office of Scientific and Technical Information (OSTI.GOV)

S.C. Jardin; C.E. Kessel; T.K. Mau

2003-10-07

The advanced tokamak is considered as the basis for a fusion power plant. The ARIES-AT design has an aspect ratio of A always equal to R/a = 4.0, an elongation and triangularity of kappa = 2.20, delta = 0.90 (evaluated at the separatrix surface), a toroidal beta of beta = 9.1% (normalized to the vacuum toroidal field at the plasma center), which corresponds to a normalized beta of bN * 100 x b/(I(sub)P(MA)/a(m)B(T)) = 5.4. These beta values are chosen to be 10% below the ideal-MHD stability limit. The bootstrap-current fraction is fBS * I(sub)BS/I(sub)P = 0.91. This leads tomore » a design with total plasma current I(sub)P = 12.8 MA, and toroidal field of 11.1 T (at the coil edge) and 5.8 T (at the plasma center). The major and minor radii are 5.2 and 1.3 m, respectively. The effects of H-mode edge gradients and the stability of this configuration to non-ideal modes is analyzed. The current-drive system consists of ICRF/FW for on-axis current drive and a lower-hybrid system for off-axis. Tran sport projections are presented using the drift-wave based GLF23 model. The approach to power and particle exhaust using both plasma core and scrape-off-layer radiation is presented.« less

Insulin sensitivity and beta-cell function in healthy cats: assessment with the use of the hyperglycemic glucose clamp.

PubMed

Slingerland, L I; Robben, J H; van Haeften, T W; Kooistra, H S; Rijnberk, A

2007-05-01

A hyperglycemic clamp (HGC) was developed for use in conscious cats. In 21 healthy, normal glucose tolerant cats glucose disposal rate (M), insulin sensitivity (ISI (HGC)), and beta-cell response (I) at arterial plasma glucose of 9 mmol.l (-1) were measured. The HGC was tolerated well and steady state glucose infusion was achieved. Compared to values reported for humans, M values for the cats were low, which appeared to relate to both a low ISI (HGC) and a low I. HGC measures correlated with fasting plasma glucose and insulin concentrations as well as with their HOMA (homeostasis model assessment) and QUICKI (quantitative insulin sensitivity check index) counterparts. Also, I and ISI (HGC) correlated with their counterparts derived from intravenous glucose tolerance tests. In conclusion, this is the first report of hyperglycemic glucose clamping in cats. The procedure (HGC) allows for measurements of glucose disposal, beta-cell response and insulin sensitivity. Compared to human data, both insulin sensitivity and insulin secretion appeared to be low in cats. This is compatible with the carnivorous nature of this species, for which insulin resistance would be advantageous during periods of restricted food availability.

Prevalence and prognostic significance of adrenergic escape during chronic beta-blocker therapy in chronic heart failure.

PubMed

Frankenstein, Lutz; Zugck, Christian; Schellberg, Dieter; Nelles, Manfred; Froehlich, Hanna; Katus, Hugo; Remppis, Andrew

2009-02-01

Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different beta-blocker agents and doses. This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual beta-blocker agents used and the dose equivalent taken, the prevalence of AE was 31-39%. Norepinephrine levels neither correlated with heart rate (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387-2.645; chi2: 15.60). We verified the presence of AE in CHF patients on chronic stable beta-blocker therapy, irrespective of the individual beta-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.

LET and ion-species dependence for cell killing and mutation induction in normal human fibroblasts.

PubMed

Tsuruoka, Chizuru; Suzuki, Masao; Fujitaka, Kazunobu

2003-10-01

We have been studying LET and ion species dependence of RBE values in cell killing and mutation induction. Normal human skin fibroblasts were irradiated with heavy-ion beams such as carbon (290 Mev/u and 135 Mev/u), neon (230 Mev/u and 400 Mev/u), silicon (490 Mev/u) and iron (500 Mev/u) ion beams, generated by Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS). Cell killing effect was detected as reproductive cell death using a colony formation assay. Mutation induction in hprt locus was detected to measure 6-thioguanine resistant colonies. The RBE-LET curves of cell killing and mutation induction were different each ion beam. So, we plotted RBE for cell killing and mutation induction as function of Z*2/beta2 instead of LET. RBE-Z*2/beta2 curves of cell killing indicated that the discrepancy of RBE-LET curves was reconciled each ion species. But RBE-Z*2/beta2 curves of mutation induction didn't corresponded between carbon- and silicon-ion beams. These results suggested that different biological endpoints may be suitable for different physical parameter, which represent the track structure of energy deposition of ion beams.

Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat

NASA Technical Reports Server (NTRS)

Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.

1986-01-01

The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

[Correlations of telomere length changing and pathogeny of keratoconus].

PubMed

Wang, Jiao-jiao; Li, Shao-wei; Wang, Yi-qiang; Wang, Ye; Zhong, Wen-xian; Zang, Xin-jie

2009-08-01

To study telomere length, senescence-associated-beta-galactosidase (SA-beta-galactosidase) and senescence marker protein-30 (SMP-30) in the stromal cells of keratoconus or normal corneas respectively, aiming finding the association of these indexes with the phenotype of keratoconus. Experiment research. 37 keratoconus lesions corneas were removed from 32 keratoconus patients who were operated in Shangdong Eye Institute between January 2006 and December 2006, and 20 normal corneas were collected from eye bank. The keratoconus corneas ages were from 13 to 34 years [mean ages (19 + or - 5) years] and the control group consists of 20 normal corneas donor ages from 9 to 30 years [mean ages (19 + or - 4) years]. And there was no statistical difference of ages between keratoconus and normal corneas. Southern blot method was utilized to detect telomere length of genomic DNA. SA-beta-galactosidase was detected by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining method respectively in keratoconus and normal corneas. Isolated mRNA from keratoconus and normal corneas were reverse-transcribed to cDNA and SMP-30 was detected using PCR with specific primers (sense: 5' ccg tgg atg cct ttg act at 3'; anti-sense: 5' caa ctt cat gc tgct ttg ga 3'). To compare normal corneas and keratoconus corneas by histopathological study. Statistical analysis by t test. The telomere length in stromal cells in keratoconus corneas were from 10.29 to 14.12 kb, mean (11.54 + or - 1.41) kb, while that of normal corneas were from 12.64 to 15.32 kb, mean (13.45 + or - 0.99) kb. The difference of telomere length in stromal cells of keratoconus and normal corneas reached a statistical significant level (t = 4.753, P < 0.05). That means the telomere length of keratoconus stroma was shorter than that of normal corneal stroma. Light microscopy revealed that collagen fibers in keratoconus corneal stroma were arranged in an irregular manner. Cells density in keratoconus stroma appeared lower than in normal ones but the decrease was not significant. The staining of SA-beta-galactosidase in the keratoconus section was evident, but there was no staining in the normal corneas. SMP-30 was not detectable with RT-PCR method in either keratoconus or normal corneas. Telomeres in the keratoconus stromas manifest higher SA-beta-galactosidase than control, implying that improper senescence might be involved in pathogenesis of keratoconus.

TGF-beta-induced apoptosis in human thyrocytes is mediated by p27kip1 reduction and is overridden in neoplastic thyrocytes by NF-kappaB activation.

PubMed

Bravo, Susana B; Pampín, Sandra; Cameselle-Teijeiro, José; Carneiro, Carmen; Domínguez, Fernando; Barreiro, Francisco; Alvarez, Clara V

2003-10-30

Millions of people worldwide suffer goiter, a proliferative disease of the follicular cells of the thyroid that may become neoplastic. Thyroid neoplasms have low proliferative index, low apoptotic index and a high incidence of metastasis. TGF-beta is overexpressed in thyroid follicular tumor cells. To investigate the role of TGF-beta in thyroid tumor progression, we established cultures of human thyrocytes from different proliferative pathologies (Grave's disease, multinodular goiter, follicular adenoma, papillary carcinoma), lymph node metastasis, and a normal thyroid sample. All cultures maintained the thyrocyte phenotype. TGF-beta induced cell-cycle arrest in all cultures, in contrast with results reported for other epithelial tumors. In deprived medium, TGF-beta induced apoptosis in normal thyrocyte cultures and all neoplastic cultures except the metastatic cultures. This apoptosis was mediated by a reduction in p27kip1 levels, inducing cell-cycle initiation. Antisense p27 expression induced apoptosis in the absence of TGF-beta. By contrast, in cells in which p27 was overexpressed, TGF-beta had a survival effect. In growth medium, a net survival effect occurs in neoplastic thyrocytes only, not normal thyrocytes, due to activation of the NF-kappaB survival program. Together, these findings suggest that (a) thyroid neoplasms are due to reduced apoptosis, not increased division, in line with the low proliferative index of these pathologies, and (b) TGF-beta induces apoptosis in normal thyrocytes via p27 reduction, but that in neoplastic thyrocytes this effect is overridden by activation of the NF-kappaB program.

Variations in Paper Electrophoretic Serum Lipoprotein Patterns in Healthy Subjects

PubMed Central

Buckley, G. C.; Little, J. A.; Csima, A.

1970-01-01

The normal variations in the paper electrophoretic lipoprotein patterns in 240 healthy Canadian males and females, aged 10 to 59 years, have been described and compared with serum cholesterol and triglyceride levels. The incidence of abnormal chylomicra, beta and pre-beta lipoproteins was similar in both sexes and increased with age in both sexes. Chylomicron bands and/or pre-beta trails from the origin occurred in 4% of subjects, pre-beta bands in 27% and “abnormally” dense beta bands in 28%. Five per cent of subjects were considered to have definite hyperlipoproteinemia, another 19% had slight and 21% had questionable hyperlipoproteinemia. Fifty-five per cent were normal. PMID:5538493

Bile alcohol metabolism in man. Conversion of 5beta-cholestane-3alpha, 7alpha,12alpha, 25-tetrol to cholic acid.

PubMed Central

Salen, G; Shefer, S; Setoguchi, T; Mosbach, E H

1975-01-01

To study the role of C25-HYDROXY BILE ALCOHOLS AS PRECURSORS OF CHOlic acid, [G-3-H]5beta-cholestane-3alpha,7alpha12alpha,25-tetrol was administered intravenously to two subjects with cerebrotendinous xanthomatosis (CTX) and two normal individuals. One day after pulse labeling, radioactivity was present in the cholic acid isolated from the bile and feces of the subjects with CTX and the bile of the normal individuals. In the two normal subjects, the sp act decay curves of [G-3-H]-cholic acid were exponential, and no traces of [G-3-H]-5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol were detected. In contrast, appreciable quantities of labeled 5beta-cholestane-3alpha,-7aopha,12alpha,25-tetrol were present in the bile and feces of the CTX subjects. The sp act vs. time curves of fecal [G-3-H]5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol and [G-3-H]-cholic acid showed a precursor-product relationship. Although these results suggest that 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol may be a precursor of cholic acid in man, the possibility that C26-hydroxy intermediates represent the normal pathway can not be excluded. PMID:1141434

Feasibility of Computed Tomography-Guided Methods for Spatial Normalization of Dopamine Transporter Positron Emission Tomography Image.

PubMed

Kim, Jin Su; Cho, Hanna; Choi, Jae Yong; Lee, Seung Ha; Ryu, Young Hoon; Lyoo, Chul Hyoung; Lee, Myung Sik

2015-01-01

Spatial normalization is a prerequisite step for analyzing positron emission tomography (PET) images both by using volume-of-interest (VOI) template and voxel-based analysis. Magnetic resonance (MR) or ligand-specific PET templates are currently used for spatial normalization of PET images. We used computed tomography (CT) images acquired with PET/CT scanner for the spatial normalization for [18F]-N-3-fluoropropyl-2-betacarboxymethoxy-3-beta-(4-iodophenyl) nortropane (FP-CIT) PET images and compared target-to-cerebellar standardized uptake value ratio (SUVR) values with those obtained from MR- or PET-guided spatial normalization method in healthy controls and patients with Parkinson's disease (PD). We included 71 healthy controls and 56 patients with PD who underwent [18F]-FP-CIT PET scans with a PET/CT scanner and T1-weighted MR scans. Spatial normalization of MR images was done with a conventional spatial normalization tool (cvMR) and with DARTEL toolbox (dtMR) in statistical parametric mapping software. The CT images were modified in two ways, skull-stripping (ssCT) and intensity transformation (itCT). We normalized PET images with cvMR-, dtMR-, ssCT-, itCT-, and PET-guided methods by using specific templates for each modality and measured striatal SUVR with a VOI template. The SUVR values measured with FreeSurfer-generated VOIs (FSVOI) overlaid on original PET images were also used as a gold standard for comparison. The SUVR values derived from all four structure-guided spatial normalization methods were highly correlated with those measured with FSVOI (P < 0.0001). Putaminal SUVR values were highly effective for discriminating PD patients from controls. However, the PET-guided method excessively overestimated striatal SUVR values in the PD patients by more than 30% in caudate and putamen, and thereby spoiled the linearity between the striatal SUVR values in all subjects and showed lower disease discrimination ability. Two CT-guided methods showed comparable capability with the MR-guided methods in separating PD patients from controls and showed better correlation between putaminal SUVR values and the parkinsonian motor severity than the PET-guided method. CT-guided spatial normalization methods provided reliable striatal SUVR values comparable to those obtained with MR-guided methods. CT-guided methods can be useful for analyzing dopamine transporter PET images when MR images are unavailable.

Feasibility of Computed Tomography-Guided Methods for Spatial Normalization of Dopamine Transporter Positron Emission Tomography Image

PubMed Central

Kim, Jin Su; Cho, Hanna; Choi, Jae Yong; Lee, Seung Ha; Ryu, Young Hoon; Lyoo, Chul Hyoung; Lee, Myung Sik

2015-01-01

Background Spatial normalization is a prerequisite step for analyzing positron emission tomography (PET) images both by using volume-of-interest (VOI) template and voxel-based analysis. Magnetic resonance (MR) or ligand-specific PET templates are currently used for spatial normalization of PET images. We used computed tomography (CT) images acquired with PET/CT scanner for the spatial normalization for [18F]-N-3-fluoropropyl-2-betacarboxymethoxy-3-beta-(4-iodophenyl) nortropane (FP-CIT) PET images and compared target-to-cerebellar standardized uptake value ratio (SUVR) values with those obtained from MR- or PET-guided spatial normalization method in healthy controls and patients with Parkinson’s disease (PD). Methods We included 71 healthy controls and 56 patients with PD who underwent [18F]-FP-CIT PET scans with a PET/CT scanner and T1-weighted MR scans. Spatial normalization of MR images was done with a conventional spatial normalization tool (cvMR) and with DARTEL toolbox (dtMR) in statistical parametric mapping software. The CT images were modified in two ways, skull-stripping (ssCT) and intensity transformation (itCT). We normalized PET images with cvMR-, dtMR-, ssCT-, itCT-, and PET-guided methods by using specific templates for each modality and measured striatal SUVR with a VOI template. The SUVR values measured with FreeSurfer-generated VOIs (FSVOI) overlaid on original PET images were also used as a gold standard for comparison. Results The SUVR values derived from all four structure-guided spatial normalization methods were highly correlated with those measured with FSVOI (P < 0.0001). Putaminal SUVR values were highly effective for discriminating PD patients from controls. However, the PET-guided method excessively overestimated striatal SUVR values in the PD patients by more than 30% in caudate and putamen, and thereby spoiled the linearity between the striatal SUVR values in all subjects and showed lower disease discrimination ability. Two CT-guided methods showed comparable capability with the MR-guided methods in separating PD patients from controls and showed better correlation between putaminal SUVR values and the parkinsonian motor severity than the PET-guided method. Conclusion CT-guided spatial normalization methods provided reliable striatal SUVR values comparable to those obtained with MR-guided methods. CT-guided methods can be useful for analyzing dopamine transporter PET images when MR images are unavailable. PMID:26147749

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rouyer-Fessard, P.; Garel, M.C.; Domenget, C.

The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with ({sup 3}H)N-ethylmaleimide. This pool of soluble alpha chains was 0.067 {plus minus} 0.017% of hemoglobin in blood of normal adult, 0.11 {plus minus} 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% inmore » the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using ({sup 3}H)N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups.« less

A test of the Hall-MHD model: Application to low-frequency upstream waves at Venus

NASA Technical Reports Server (NTRS)

Orlowski, D. S.; Russell, C. T.; Krauss-Varban, D.; Omidi, N.

1994-01-01

Early studies suggested that in the range of parameter space where the wave angular frequency is less than the proton gyrofrequency and the plasma beta, the ratio of the thermal to magnetic pressure, is less than 1 magnetohydrodynamics provides an adequate description of the propagating modes in a plasma. However, recently, Lacombe et al. (1992) have reported significant differences between basic wave characteristics of the specific propagation modes derived from linear Vlasov and Hall-magnetohydrodynamic (MHD) theories even when the waves are only weakly damped. In this paper we compare the magnetic polarization and normalization magnetic compression ratio of ultra low frequency (ULF) upstream waves at Venus with magnetic polarization and normalized magnetic compression ratio derived from both theories. We find that while the 'kinetic' approach gives magnetic polarization and normalized magnetic compression ratio consistent with the data in the analyzed range of beta (0.5 less than beta less than 5) for the fast magnetosonic mode, the same wave characteristics derived from the Hall-MHD model strongly depend on beta and are consistent with the data only at low beta for the fast mode and at high beta for the intermediate mode.

Expression and in vitro regulation of integrins by normal human urothelial cells.

PubMed

Southgate, J; Kennedy, W; Hutton, K A; Trejdosiewicz, L K

1995-08-01

Integrins are thought to be essential adhesion receptors for the maintenance of tissue histioarchitecture. The purpose of this study was to determine integrin expression patterns in the human stratified transitional epithelium of the urinary tract (urothelium). In situ expression patterns were compared with in vitro expression, using a normal cell culture model system in which the effects of cell stratification can be studied independently of differentiation. By immunohistological criteria, the urothelia of bladder, ureter and renal pelvis expressed alpha 2 beta 1 and alpha 3 beta 1 integrins in all layers at intercellular junctions, and cytoplasmically in the lower strata. By contrast, alpha 6 beta 4 and occasionally alpha v beta 4 were expressed only by basal cells and localised to the basal lamina. These expression patterns were unaltered in specimens where an inflammatory cell infiltrate was present. In long-term cultures of normal urothelial cells maintained in a low-Ca++ serum-free medium, the monolayer cultures expressed alpha 2 beta 1, alpha 3 beta 1 and alpha 5 beta 1 integrins at intercellular junctions and in cytoplasmic inclusions, whereas alpha 6 beta 4 was distributed in a random pattern over the substratum. Increasing exogenous Ca++ concentrations induced cell stratification and desmosome formation, but not cytodifferentiation. Under these conditions, alpha 6 beta 4 became cell-, rather than substratum-associated, localising particularly to filopodia and lamellipodia. Quantitation of integrin expression by flow cytometry confirmed increased surface expression of alpha 6 beta 4 in high Ca++ media, and also of alpha 3 and alpha 5, but not alpha 2, subunits. These results suggest that alpha 2 beta 1 and alpha 3 beta 1 integrins, although differentially regulated, are mainly involved in homotypic cell-cell interactions and the maintenance of a stratified morphology, whereas alpha 6 beta 4 is the principal integrin involved in substratum adhesion.

Hb Molfetta [beta126(H4)Val-->Leu, GTG-->CTG]: a new, silent, neutral beta chain variant found in an Italian woman.

PubMed

Qualtieri, Antonio; Le, Pera Maria; Pedace, Vera; Magariello, Angela; Brancati, Carlo

2002-02-01

We have identified a new neutral hemoglobin variant in a pregnant Italian woman, that resulted from a GTG-->CTG replacement at codon 126 of the beta chain, corresponding to a Val-->Leu amino acid change at position beta126(H4). Thermal and isopropanol stability tests were normal and there were no abnormal clinical features. Routine electrophoretic and ion exchange chromatographic methods for hemoglobin separation failed to show this variant, but reversed phase high performance liquid chromatography revealed an abnormal peak eluting near the normal beta chain. No abnormal tryptic peptide was revealed on the high performance liquid chromatographic elution pattern of the total globin digest. The mutation was determined at the DNA level by amplification of the three beta exons by polymerase chain reaction and direct sequencing of one exon that showed an abnormal migration on single strand conformational polymorphism analysis.

Triplex DNA-binding proteins are associated with clinical outcomes revealed by proteomic measurements in patients with colorectal cancer

PubMed Central

2012-01-01

Background Tri- and tetra-nucleotide repeats in mammalian genomes can induce formation of alternative non-B DNA structures such as triplexes and guanine (G)-quadruplexes. These structures can induce mutagenesis, chromosomal translocations and genomic instability. We wanted to determine if proteins that bind triplex DNA structures are quantitatively or qualitatively different between colorectal tumor and adjacent normal tissue and if this binding activity correlates with patient clinical characteristics. Methods Extracts from 63 human colorectal tumor and adjacent normal tissues were examined by gel shifts (EMSA) for triplex DNA-binding proteins, which were correlated with clinicopathological tumor characteristics using the Mann-Whitney U, Spearman’s rho, Kaplan-Meier and Mantel-Cox log-rank tests. Biotinylated triplex DNA and streptavidin agarose affinity binding were used to purify triplex-binding proteins in RKO cells. Western blotting and reverse-phase protein array were used to measure protein expression in tissue extracts. Results Increased triplex DNA-binding activity in tumor extracts correlated significantly with lymphatic disease, metastasis, and reduced overall survival. We identified three multifunctional splicing factors with biotinylated triplex DNA affinity: U2AF65 in cytoplasmic extracts, and PSF and p54nrb in nuclear extracts. Super-shift EMSA with anti-U2AF65 antibodies produced a shifted band of the major EMSA H3 complex, identifying U2AF65 as the protein present in the major EMSA band. U2AF65 expression correlated significantly with EMSA H3 values in all extracts and was higher in extracts from Stage III/IV vs. Stage I/II colon tumors (p = 0.024). EMSA H3 values and U2AF65 expression also correlated significantly with GSK3 beta, beta-catenin, and NF- B p65 expression, whereas p54nrb and PSF expression correlated with c-Myc, cyclin D1, and CDK4. EMSA values and expression of all three splicing factors correlated with ErbB1, mTOR, PTEN, and Stat5. Western blots confirmed that full-length and truncated beta-catenin expression correlated with U2AF65 expression in tumor extracts. Conclusions Increased triplex DNA-binding activity in vitro correlates with lymph node disease, metastasis, and reduced overall survival in colorectal cancer, and increased U2AF65 expression is associated with total and truncated beta-catenin expression in high-stage colorectal tumors. PMID:22682314

Serum amyloid protein A concentration in cryopyrin-associated periodic syndromes patients treated with interleukin-1 beta antagonist.

PubMed

Pastore, Serena; Paloni, Giulia; Caorsi, Roberta; Ronfani, Luca; Taddio, Andrea; Lepore, Loredana

2014-01-01

Cryopyrin-associated periodic syndromes (CAPS) are a group of chronic, relapsing autoinflammatory disorders which may be complicated by systemic AA amyloidosis. The aim of our study was to evaluate serum amyloid protein A (SAA) level in CAPS patients treated with Interleukin-1beta (IL-1β) antagonist and to correlate its level with treatment response. All patients of CAPS Italian Register treated with IL-1β inhibitor were enrolled. SAA levels before starting therapy, and at last visit were evaluated. Patients were then divided in complete responders and partial responders. Twenty-five patients were enrolled. SAA level before starting therapy was increased (median 118.5 mg/L, IQR 96.4-252.8; normal value <6.4 mg/L), while at last visit SAA was significantly reduced (median 4.3 mg/L, IQR 2.3-12.7) (p<0.001). However 12 patients still presented SAA levels beyond normal range, 10/25 patients (40%) showed a complete response to treatment. Conversely, 15 patients presented only a partial response, of which 12 for increased SAA value and 3 for increased CRP value. Patients with partial response had SAA values significantly higher than patients with complete response (median 12.6 mg/L; IQR 8.3-20.0 vs. 2.7 mg/L; IQR 1.6-4.1, p<0.001). Our results confirm the long term efficacy of anti IL-1β treatment in CAPS and the decrease of SAA levels; however 48% of patients still presented SAA elevation despite treatment. The real risk of these patients in developing amyloidosis is not clear but the persistent increase of SAA needs a close follow-up.

Effects of a beta-adrenergic blocking agent timolol on intra ocular pressure responses induced by stimulation of cervical sympathetic nerve in the cat.

PubMed

Naito, A; Izumi, H; Karita, K; Tamai, M

2001-12-01

We clarified whether the intraocular pressure (IOP) response elicited by stimulation of the cervical sympathetic nerve (CSN) is influenced by changes in the baseline of IOP level and by beta-adrenergic blockade. The CSN was stimulated electrically for 30 seconds (10 V, 0.1-100 Hz, 2 milliseconds pulse duration) in urethane (100 mg/kg i.v.)-chloralose (50 mg/kg i.v.)-anesthetized, paralyzed cats. The IOP was monitored manometrically, and a controlled saline infusion was delivered into the anterior chamber to gradually increase IOP. CSN stimulation was delivered at the various baseline IOP levels so obtained. When required, a beta-adrenergic blocker timolol (2%) was delivered into the conjunctival cul-de-sac. The normal IOP in our cats was 25+/-3 mmHg. This value decreased transiently on CSN stimulation. The amplitude of this IOP response depended on stimulus frequency and the pre-stimulus baseline IOP level. Topical administration of timolol increased the IOP response to CSN stimulation at a given baseline level. These results suggest that beta-adrenergic blockade increases the alpha-adrenergic mediated-IOP reduction elicited by CSN stimulation at given baseline IOP level.

Differential regulation of thyrotropin subunit apoprotein and carbohydrate biosynthesis by thyroid hormone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, T.; Weintraub, B.D.

1985-04-01

The regulation of TSH apoprotein and carbohydrate biosynthesis by thyroid hormone was studied by incubating pituitaries from normal and hypothyroid (3 weeks post-thyroidectomy) rats in medium containing (/sup 14/C)alanine and (/sup 3/H) glucosamine. After 6 h, samples were sequentially treated with anti-TSH beta to precipitate TSH and free TSH beta, anti-LH beta to clear the sample of LH and free LH beta, then anti-LH alpha to precipitate free alpha-subunit. Total proteins were acid precipitated. All precipitates were subjected to electrophoresis on sodium dodecyl sulfate-polyacrylamide gels, which were then sliced and assayed by scintillation spectrometry. In hypothyroid pituitaries plus medium, (/supmore » 14/C)alanine incorporation in combined and free beta-subunits was 26 times normal and considerably greater than the 3.4-fold increase seen in total protein; combined and free alpha-subunits showed no specific increase in apoprotein synthesis. (/sup 3/H)Glucosamine incorporation in combined alpha- and beta-subunits in hypothyroid samples was 13 and 21 times normal, respectively, and was greater than the 1.9-fold increase in total protein; free alpha-subunit showed no specific increase in carbohydrate synthesis. The glucosamine to alanine ratio, reflecting relative glycosylation of newly synthesized molecules, was increased in hypothyroidism for combined alpha-subunits, but not for combined beta-subunits, free alpha-subunits, or total proteins. In summary, short term hypothyroidism selectively stimulated TSH beta apoprotein synthesis and carbohydrate synthesis of combined alpha- and beta-subunits. Hypothyroidism also increased the relative glycosylation of combined alpha-subunit. Thus, thyroid hormone deficiency appears to alter the rate-limiting step in TSH assembly (i.e. beta-subunit synthesis) as well as the carbohydrate structure of TSH, which may play important roles in its biological function.« less

Determination of Clara cell protein urinary elimination as a marker of tubular dysfunction.

PubMed

Martín-Granado, Ascensión; Vázquez-Moncholí, Carmen; Luis-Yanes, María Isabel; López-Méndez, Marisela; García-Nieto, Víctor

2009-04-01

Clara cell 16-kDa protein (CC16) is a protein expressed primarily by the bronchial cells. It is rapidly eliminated by glomerular filtration, reabsorbed almost entirely, and catabolized in proximal tubule cells. To date, normal values for urinary CC16 in healthy children have not been determined. We have studied 63 pediatric patients (mean age 8.17 +/- 3.91 years) and 31 healthy children (control group; mean age 8.83 +/- 3.65 years). In the control group, the CC16/creatinine ratio was 1.22 +/- 1.52 microg/g. In 16 out of 31 control children, the value of the ratio was zero. Fourteen patients (22.2%) showed a high CC16/creatinine ratio; in contrast, among these same patients, the ratio N-acetyl-beta-D: -glucosaminidase (NAG)/creatinine was elevated in seven cases (11.1%) and the ratio beta2-microglobulin/creatinine was elevated in seven cases (11.1%). The three parameters were in agreement in 51 patients (80.9%). Among the patients, the CC16/creatinine ratio was correlated with both the beta2-microglobulin/creatinina ratio (r = 0.76, P < 0.001) and the NAG/creatinine ratio (r = 0.6, P < 0.001). Our findings indicate that CC16 is a good marker of proximal tubular function in childhood. The highest observed values were in children with proximal tubulopathies, in children with chronic renal failure, and in those treated with cyclosporine.

Influence of insulin on beta-endorphin plasma levels in obese and normal weight subjects.

PubMed

Brunani, A; Pincelli, A I; Pasqualinotto, L; Tibaldi, A; Baldi, G; Scacchi, M; Fatti, L M; Cavagnini, F

1996-08-01

To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

[Changes of proinflammatory cytokines and their receptors in serum from patients with pulmonary tuberculosis].

PubMed

Tang, Shenjie; Xiao, Heping; Fan, Yihu; Wu, Furong; Zhang, Zhongshun; Li, Hong; Yang, Yan

2002-06-01

OBJECTIVE To investigate the characteristics and clinical value of serum tumor necrosis factor-alpha (TNF-alpha) and its receptor (sTNF-R), interleukin-1beta(IL-1beta) and its receptor(IL-1R), interleukin-6(IL-6) and its receptor(IL-6R) in patients with pulmonary tuberculosis, and to evaluate their role in the immunopathogenesis of tuberculosis. METHODS The serum levels of TNF-alpha, sTNF-R Iota IL-1beta,IL-1R, IL-6 and IL-6R were measured using the sandwich ABC-ELISA method in 41 cases of active tuberculosis, 21 cases of inactive tuberculosis and 20 normal controls. The serum levels of the cytokines in 17 cases of active tuberculos is were followed. RESULTS The serum levels of TNF-alpha sTNF-RIota IL-1beta,IL-1R, IL-6 IL-6R and the TNF-alpha/sTNF-RIota ratio were significantly higher in both the active and the inactive tuberculosis groups than those in normal controls (P <0.01 approximately 0.05). The TNF-alpha sTNF-R Iota IL-1 beta, IL-1R, IL-6 IL-6R levels and the TNF-alpha/sTNF-R Iota ratio in the active tuberculosis group were significantly higher than those in the inactive tuberculosis(P <0.01 approximately 0.05). The serum levels of TNF-alpha sTNF-R Iota, IL-1beta and IL-6 and the TNF-alpha,/sTNF-R Iota ratio were significantly lower in cavernous tuberculosis than those in non- cavernous tuberculosis (P < 0.01 approximately 0.05). After 2 months' antituberculosis treatment, the serum levels of TNF-alpha,sTNF-R Iota IL-1 beta, IL-1R,IL-6, IL-6R and the TNF-alpha/sTNF-R Iota ratio in 15(15/17) cases were significantly lower than those before treatment(P < 0.01 approximately 0.05). CONCLUSIONS TNF-alpha, IL-1 beta, IL-6 and their receptors may be involved in the immunopathogenesis of tuberculosis. Measuring the serum levels of proinflammatory cytokines and their receptors may be useful in evaluating the activity, the clinical pattern, and the prognosis of the disease and monitoring the clinical effect of antituberculous therapy.

EEG Alpha and Beta Activity in Normal and Deaf Subjects.

ERIC Educational Resources Information Center

Waldron, Manjula; And Others

Electroencephalogram and task performance data were collected from three groups of young adult males: profoundly deaf Ss who signed from an early age, profoundly deaf Ss who only used oral (speech and speedreading) methods of communication, and normal hearing Ss. Alpha and Beta brain wave patterns over the Wernicke's area were compared across…

Expression of the leukemia-associated CBF{beta}/SMMHC chimeric gene causes transformation of 3T3 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hajra, A.; Liu, P.; Collins, E.S.

1994-09-01

A pericentric inversion of chromosome 16 (inv(16)(p13;q22)) is consistently seen in acute myeloid leukemia of the M4Eo subtype. This inversion fuses almost the entire coding region of the gene encoding of the {beta} subunit of the heterodimeric transcription factor CBF/PEBP2 to the region of the MYH11 gene encoding the rod domain for the smooth muscle myosin heavy chain (SMMHC). To investigate the biological properties of the CBF{beta}/SMMHC fusion protein, we have generated 3T3 cell lines that stably express the CBF{beta}/SMMHC chimeric cDNA or the normal, nonchimeric CBF{beta} and SMMHC cDNAs. 3T3 cells expressing CBF{beta}/SMMHC acquire a transformed phenotype, as indicatedmore » by altered cell morphology, formation of foci, and growth in soft agar. Cells constitutively overexpressing the normal CBF{beta} cDNA or the rod region of SMMHC remain nontransformed. Western blot analysis using antibodies to CBF{beta} and the SMMHC rod demonstrates that stably transfected cells express the appropriate chimeric or normal protein. Electrophoretic mobility shift assays reveal that cells transformed by the chimeric cDNA do not have a CBF-DNA complex of the expected mobility, but instead contain a large complex with CBF DNA-binding activity that fails to migrate out of the gel wells. In order to define the regions of CBF{beta}/SMMHC necessary for 3T3 transformation, we have stably transfected cells with mutant CBF{beta}/SMMHC cDNAs containing various deletions of the coding region. Analysis of these cell lines indicates that the transformation property of CBF{beta}/SMMHC requires regions of CBF{beta} known to be necessary for association with the DNA-binding CBF{alpha} subunit, and also requires an intact SMMHC carboxyl terminus, which is necessary for formation of the coiled coil domain of the myosin rod.« less

Specific signals involved in the long-term maintenance of radiation-induced fibrogenic differentiation: a role for CCN2 and low concentration of TGF-beta1.

PubMed

Haydont, Valérie; Riser, Bruce L; Aigueperse, Jocelyne; Vozenin-Brotons, Marie-Catherine

2008-06-01

The fibrogenic differentiation of resident mesenchymal cells is a key parameter in the pathogenesis of radiation fibrosis and is triggered by the profibrotic growth factors transforming growth factor (TGF)-beta1 and CCN2. TGF-beta1 is considered the primary inducer of fibrogenic differentiation and is thought to control its long-term maintenance, whereas CCN2 is considered secondary effector of TGF-beta1. Yet, in long-term established fibrosis like that associated with delayed radiation enteropathy, in situ TGF-beta1 deposition is low, whereas CCN2 expression is high. To explore this apparent paradox, cell response to increasing doses of TGF-beta1 was investigated in cells modeling initiation and maintenance of fibrosis, i.e., normal and fibrosis-derived smooth muscle cells, respectively. Activation of cell-specific signaling pathways by low TGF-beta1 doses was demonstrated with a main activation of the Rho/ROCK pathway in fibrosis-derived cells, whereas the Smad pathway was mainly activated in normal cells. This leads to subsequent and cell-specific regulation of the CCN2 gene. These results suggested a specific profibrotic role of CCN2 in fibrosis-initiated cells. Furthermore, the modulation of CCN2 expression by itself and the combination of TGF-beta1 and CCN2 was investigated in fibrosis-derived cells. In fibrosis-initiated cells CCN2 triggered its autoinduction; furthermore, low concentration of TGF-beta1-potentiated CCN2 autoinduction. Our findings showed a differential requirement and action of TGF-beta1 in the fibrogenic response of normal vs. fibrosis-derived cells. This study defines a novel Rho/ROCK but Smad3-independent mode of TGF-beta signaling that may operate during the chronic stages of fibrosis and provides evidence of both specific and combinatorial roles of low TGF-beta1 dose and CCN2.

Expression of HSP27, HSP72 and MRP proteins in in vitro co-culture of colon tumour cell spheroids with normal cells after incubation with rhTGF- beta1 and/or CPT-11.

PubMed

Paduch, Roman; Jakubowicz-Gil, Joanna; Kandefer-Szerszen, Martyna

2009-12-01

We studied the expression of inducible heat shock protein (HSP27, HSP72) and multidrug-resistance protein (MRP) in co-cultures of human colon carcinoma cell spheroids obtained from different grades of tumour with normal human colon epithelium, myofibroblast and endothelial cell monolayers. We also measured the influence of recombinant human transforming growth factor beta1 (rhTGF-beta1) and camptothecin (CPT-11), added as single agents or in combination, on the levels of the HSPs, MRP, interleukin (IL)-6 and nitric oxide (NO). An immunoblotting analysis with densitometry showed that rhTGF-beta1 and/or CPT-11 increased HSP27, HSP72 and MRP expression in tumour cells and myofibroblasts, as well as in co-cultures compared with appropriate controls. By contrast, in colonic epithelium, inhibition of HSPs and MRP was comparable with that of the control. In endothelial cells, HSP72 was undetectable. Direct interaction of colon tumour spheroids with normal myofibroblasts caused a significant, tumour-grade dependent increase in IL-6 production. Production of IL-6 was significantly lowered by rhTGF-beta1 and/or CPT-11. Tumour cell spheroids cultivated alone produced larger amounts of NO than normal cells. In co-culture, the level of the radical decreased compared with the sum of NO produced by the monocultures of the two types of cells. rhTGF-beta1 and/or CPT-11 decreased NO production both in tumour and normal cell monocultures and their co-cultures. In conclusion, direct interactions between tumour and normal cells influence the expression of HSP27, HSP72 and MRP, and alter IL-6 and NO production. rhTGF-beta1 and/or CPT-11 may potentate resistance to chemotherapy by increasing HSP and MRP expression but, on the other hand, they may limit tumour cell spread by decreasing the level of some soluble mediators of inflammation (IL-6 and NO).

17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean population.

PubMed

Rosler, Ariel

2006-08-01

Eighty-five males with 17 beta-HSD3 were identified among a highly inbred Arab population in Israel and 57 studied over a period of 25 years. The founders of this defect originated in the mountainous regions of present Lebanon and Syria, but most of the families now live in Jerusalem, Hebron, the Tel-Aviv area and, in particular, in Gaza, where the frequency of affected males is estimated at 1 in 100 to 150. Affected individuals are born with ambiguity of the external genitalia and reared as females until puberty. Thereafter marked virilization occurs, leading in many cases to the spontaneous adoption of a male gender identity and role. Adults develop a male habitus with abundant body hair and beard and the phallus and testes enlarge to adult proportions. Gender reassignment in infancy was only possible when enough erectile tissue was present at birth and developed into a normal size penis with testosterone. 17 beta-HSD3 deficiency can be reliably diagnosed by endocrine evaluation and mutation analysis. In adults the defect is characterized by markedly increased concentrations of androstenedione (A) with borderline low to normal testosterone (T) levels and a high A/T ratio. 5a-dihydrotestosterone (DHT) concentrations are moderately decreased, normal or high and dehydroepiandrosterone (DHEA) levels are high. The estrogen pathway is also impaired, even though both estrone (E-1) and estradiol-17 beta (E-2) levels are high. Children have low basal levels of all androgens, but the defect may be demonstrated after prolonged stimulation with human chorionic gonadotropin (HCG). LH and FSH levels are very high after puberty and normal in childhood. 17 beta-HSD3 isozyme is encoded by the chromosome 9q22 17 beta-HSD3 gene and expressed exclusively in testes. A point mutation in exon 3, codon 80 of the 17 beta-HSD3 gene, R80Q, caused by a single base substitution from CGG ( arginine) to CAG ( glutamine) was identified in both alleles of 24 individuals from 9 extended Arab families from Gaza, Jerusalem and Lod-Ramle. Twenty-one homozygote males (46,XY) were MPH with testicular 17 beta-HSD3 deficiency whereas the three homozygote females (46,XX) were asymptomatic, had normal internal and external genitalia, normal sexual development and revealed no biochemical evidence of 17 beta-HSD3 deficiency. The molecular pattern is compatible with an autosomal recessive mode of inheritance, sex dependent.

[Renal handling of beta2 microglobulin. Its significance in carriers of adolescent nephronophthisis (NPH3)].

PubMed

Fernández, Carmen; Araque, Carolina; Méndez, Jorge; Angulo, Luisa; Fargier, Bernardo

2007-06-01

The adolescent nephronophthisis (NPH3) is a variant of the nephronophthisis. In Venezuela, one to three patients have been registered each year, all of them belonging to the same family tree. The objective of this study was to evaluate the function of the proximal convoluted tubule in NPHP3 carriers; using the beta2M as biological marker. Eight carriers, 7 heterozygotes and 1 homozygote, with normal renal function were compared with a 10 healthy subjects (control group). Serum beta2 microglobulin (beta2M), urinary beta2M, the quotient urinary beta2M/urinary creatinine and the beta2M fractional excretion were determinated. The filtered beta2M and the percentage of reabsortion were calculated. We observed an increase in the plasmatic concentration of beta2M but not related with a decrease of the glomerular filtration. The urinary beta2M, the beta2M/urinary creatinine relation and the fractional excretion of beta2M were normal. The filtered load of beta2M was elevated without increase in the excretion or percentage of reabsortion. We conclude that in our group of NPH3 carriers, functional changes in the proximal convoluted tubule, when measured by urinary excretion of beta2M, were absent. This finding suggests the existence of other mechanism of uptake or degradation of the substance in the proximal convoluted tubule, which have yet to be elucidated.

Functional integrins from normal and glycosylation-deficient baby hamster kidney cells. Terminal processing of asparagine-linked oligosaccharides is not correlated with fibronectin-binding activity.

PubMed

Koyama, T; Hughes, R C

1992-12-25

We have examined the properties of the alpha 5 beta 1 integrin of baby hamster kidney (BHK) cells, a ricin-resistant variant Ric14 lacking N-acetylglucosaminyl transferase I, and hence unable to complete assembly of hybrid- or complex-type N-glycans, and BHK cells treated with 1-deoxymannojirimycin (dMM), an inhibitor of Golgi mannosidases involved in the initial processing of N-glycan precursors. Comparable amounts of alpha 5 beta 1 integrin were isolated from these cells by chromatography of detergent extracts on a fibronectin cell-binding fragment affinity column and elution with EDTA. The alpha 5 beta 1 integrin obtained from normal BHK cells by fibronectin affinity chromatography contained mainly endoglycosidase H-resistant oligosaccharides, whereas in RicR14 cells or dMM-treated BHK cells these were entirely endoglycosidase H-sensitive. Analysis of lactoperoxidase labeled or long term biosynthetically 35S-labeled proteins from cultures of normal or glycosylation deficient cells showed similar steady state levels of alpha 5 beta 1 integrin and expression at the cell surface. Pulse-chase experiments in normal BHK cells showed rapid conversion of the alpha 5 subunit into a mature form containing oligosaccharides resistant to endoglycosidase H and slower maturation of a precursor beta 1 subunit, as in other cell types. In Ric14 cells the precursor beta 1 subunit was found to carry glycans larger than the fully processed Man5GlcNAc2 glycan of the mature subunit, indicating that the bulk precursor pool had not been translocated into the cis-Golgi compartment containing mannosidase I. We conclude that in BHK cells terminal oligosaccharide processing of alpha 5 beta 1 integrin subunits is not required for dimer formation, surface expression, and fibronectin binding, and that expression of the glycosylation defect of Ric14 cells on the alpha 5 beta 1 integrin does not account for the reduced adhesiveness of these cells on fibronectin compared with normal and dMM-treated BHK cells.

Anxiety and beta-adrenergic receptor function in a normal population.

PubMed

Kang, Eun-Ho; Yu, Bum-Hee

2005-06-01

Many studies have shown a close relationship between anxiety and beta-adrenergic receptor function in patients with anxiety disorders. This study examined the relationship between beta-adrenergic receptor function and anxiety levels in a normal population. Subjects for this study included 36 men and 44 women between the ages of 20 and 40 years whose Body Mass Index (BMI) was between 18 and 26. All of them were healthy subjects who had no previous history of medical or psychiatric illnesses. The authors measured the Spielberger State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Chronotropic 25 Dose (CD25) of isoproterenol, previously developed to assess in vivo beta-adrenergic receptor sensitivity. We also examined correlations between log normalized CD25 and mood states. The mean of CD25 was 2.64+/-1.37 mug and the mean of CD25 in men was significantly higher (i.e., lower beta-adrenergic receptor sensitivity) than that of women (3.26+/-1.35 vs. 2.14+/-1.17 microg; t = 3.99, p < 0.001). CD25 showed negative correlations with STAI state anxiety (r = -0.344, p = 0.002), trait anxiety (r = -0.331, p = 0.003), and BDI (r = -0.283, p = 0.011). CD25 was positively correlated with BMI (r = 0.423, p < 0.001) and age (r = 0.271, p = 0.015). In stepwise multiple regression analyses, 34% of the variance in CD25 was accounted for by sex, state anxiety, and BMI. The sensitivity of beta-adrenergic receptors increased as anxiety levels became higher in a normal population. Thus, the relationship between anxiety and beta-adrenergic receptor function in healthy subjects may be different from that of patients with anxiety disorders.

Isomeric forms of specifically. beta. -subunit labeled mitochondrial F/sub 1/-adenosinetriphosphatase with different properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, J.H.; Wu, J.C.; Joshi, V.

1986-05-01

Treatment of the mitochondrial F/sub 1/-ATPase (MF/sub 1/) containing 1 specific 7-(4-nitro-2,1,3-(/sup 14/C)benzoxadiazolyl)-label (NBD) per enzyme molecule with acetylcysteine (AC) shows that the ratio r of specific ATPase activity of (O-NBD)/sub n/MF/sub 1/ to that of the control MF/sub 1/ increases linearly with the number of labels removed by AC from r < 0.1 to r > 0.9 and that dr/dn approx. = -1 as expected from specific labeling of an essential Tyr in the catalytic ..beta..' subunit. The r value of this labeled enzyme can also be increased 10-fold by LiCl-induced rearrangement of its subunits without removing any ofmore » the label. Similar treatment of the rearranged (O-NBD)/sub n/MF/sub 1/ shows that only a fraction of its radioactive labels can be removed at the normal rate by AC with dr/dn approx. = -1. The remaining labels have little inhibitory effect and are removed at much slower rates by AC with dr/dn approx. = 0. If the reaction with the rearranged (O-NBD)/sub n/MF/sub 1/ is terminated by gel-filtration when most of the labels on ..beta..' have been removed, an isomeric form of the covalently labeled enzyme is obtained with n > 0.5 but r approx. = 1, indicating that its labels are on the subunits (..beta..'') which do not catalyze directly. Incubation of O-..beta..'-NBD-MF/sub 1/ and O-BETA''-NBD-MF/sub 1/ at pH 8.95 gives N-..beta..'-NBD-MF/sub 1/ and N-..beta..''-NBD-MF/sub 1/ respectively with different fluorescence quenching characteristics.« less

Automated electroencephalography system and electroencephalographic correlates of space motion sickness, part 4

NASA Technical Reports Server (NTRS)

Frost, J. D., Jr.

1977-01-01

Comparative data for further assessments of the EEG alterations seen during Skylab are elaborated. The variability of alpha, beta, theta, and delta EEG characteristics was analyzed with quantitative computer techniques in a group of six normal individuals over a period of two months, and the EEG effects of a prolonged period of bed rest were evaluated in two subjects. The results confirm that the inflight EEG changes seen during Skylab are statistically significant, but the absolute values obtained for the various parameters do not exceed the maximal range expected in a normal population. Further, the EEG manifestations of extended bed rest do not appear similar to those of space flight.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptormore » density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.« less

Gender impact on first trimester markers in Down syndrome screening.

PubMed

Larsen, Severin Olesen; Wøjdemann, Karen R; Shalmi, Anne-Cathrine; Sundberg, Karin; Christiansen, Michael; Tabor, Ann

2002-12-01

The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free betahCG, being 16% higher for female than for male fetuses. Copyright 2002 John Wiley & Sons, Ltd.

Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias.

PubMed

Haidas, S; Zannos-Mariolea, L; Matsaniotis, N

1975-12-01

The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.

TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Eun Jee; Chun, Ji Na; Jung, Sun-Ah

2011-11-18

Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology inmore » pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases.« less

Inhibition of 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) activity of human lung microsomes by genistein, daidzein, coumestrol and C(18)-, C(19)- and C(21)-hydroxysteroids and ketosteroids.

PubMed

Blomquist, Charles H; Lima, Paul H; Hotchkiss, John R

2005-07-01

Epidemiologic data suggest a relationship between dietary intake of phytochemicals and a lower incidence of some cancers. Modulation of steroid hormone metabolism has been proposed as a basis for this effect. It has been shown that aromatase, 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) are inhibited by the isoflavones, genistein and daidzein, and by coumestrol. In general, the extent of inhibition has been expressed in terms of IC50-values, which do not give information as to the pattern of inhibition, i.e., competitive, non-competitive, or mixed. Less is known of the effects of these compounds on 3alpha-HSD. The human lung is known to have a high level of 17beta-HSD and 3alpha-HSD activity. During the course of studies to characterize both activities in normal and inflamed lung and lung tumors we noted that 3alpha-HSD activity with 5alpha-DHT of microsomes from normal, adult lung was particularly susceptible to inhibition by coumestrol. To clarify the pattern of inhibition, the inhibition constants Ki and K'i were evaluated from plots of 1/v versus [I] and [S]/v versus [I]. Genistein, daidzein and coumestrol gave mixed inhibition patterns versus both 5alpha-DHT and NADH. In contrast, 5alpha-androstane-3,17-dione and 5alpha-pregnane-3,20-dione were competitive with 5alpha-DHT. NAD inhibited competitively with NADH. Our findings demonstrate that phytochemicals have the potential to inhibit 5alpha-DHT metabolism and thereby affect the androgen status of the human lung. The observation of a mixed inhibition pattern suggests these compounds bind to more than one form of the enzyme within the catalytic pathway.

Cerebral utilization of glucose, ketone bodies and oxygen in starving infant rats and the effect of intrauterine growth retardation.

PubMed

Dahlquist, G

1976-10-01

Cerebral arteriovenous differences of acetoacetate, D-beta-hydroxybutyrate, glucose, lactate and oxygen and brain DNA content was measured at 20 days of age in intrauterine growth retarded (IUGR) rats and normal littermates after 48 and 72 h of starvation. Cerebral blood flow (CBF) was measured with labeled microspheres in other comparable groups of IUGR and control rats. CBF was similar in IUGR and normal littermates (0.57+/-0.09 and 0.58+/-0.10 ml/min respectively). After 48 h of starvation, arterial glucose was significantly lower in IUGR than control animals but the arterial concentrations of ketone bodies were similar. After 48 h of starvation, cerebral arteriovenous difference of beta-hydroxybutyrate was significantly higher in control than IUGR rats also when expressed per mg brain DNA as was the fractional uptake of D-beta-hydroxybutyrate. After 72 h of starvation, arterial concentrations of ketone bodies were significantly lower in IUGR rats than controls but the fractional uptake of D-beta-hydroxybutyrate was increased compared to IUGR rats starved for 48 h. The average percentage of calculated total substrate uptake (mumol/min) accounted for by ketone bodies increased in control animals from 31.1% after 48 h of starvation to 41.0% after 72 h of starvation. In IUGR rats these percentage values were 26.5 and 25.7 respectively. After 72 h of starvation the fraction of total cerebral uptake of substrates accounted for by ketone bodies was significantly higher in control that IUGR rats. As total cerebral uptake of substrates was similar between IUGR and control animals it is concluded that IUGR rats are more dependent on glucose as a substrate for the brain during starvation.

Integrins (alpha7beta1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy.

PubMed Central

Vachon, P H; Xu, H; Liu, L; Loechel, F; Hayashi, Y; Arahata, K; Reed, J C; Wewer, U M; Engvall, E

1997-01-01

Mutations in genes coding for dystrophin, for alpha, beta, gamma, and delta-sarcoglycans, or for the alpha2 chain of the basement membrane component merosin (laminin-2/4) cause various forms of muscular dystrophy. Analyses of integrins showed an abnormal expression and localization of alpha7beta1 isoforms in myofibers of merosin-deficient human patients and mice, but not in dystrophin-deficient or sarcoglycan-deficient humans and animals. It was shown previously that skeletal muscle fibers require merosin for survival and function (Vachon, P.H., F. Loechel, H. Xu, U.M. Wewer, and E. Engvall. 1996. J. Cell Biol. 134:1483-1497). Correction of merosin deficiency in vitro through cell transfection with the merosin alpha2 chain restored the normal localization of alpha7beta1D integrins as well as myotube survival. Overexpression of the apoptosis-suppressing molecule Bcl-2 also promoted the survival of merosin-deficient myotubes, but did not restore a normal expression of alpha7beta1D integrins. Blocking of beta1 integrins in normal myotubes induced apoptosis and severely reduced their survival. These findings (a) identify alpha7beta1D integrins as the de facto receptors for merosin in skeletal muscle; (b) indicate a merosin dependence for the accurate expression and membrane localization of alpha7beta1D integrins in myofibers; (c) provide a molecular basis for the critical role of merosin in myofiber survival; and (d) add new insights to the pathogenesis of neuromuscular disorders. PMID:9312189

Spectroscopic study of the star Canum Venat (G0)

NASA Astrophysics Data System (ADS)

Mentese, H. H.

In this work the effective temperature and surface gravity of the star BetaCVn were determined by means of the theoretical profiles calculated by De Jager and Neven (1967-1968). The best agreement was obtained for T(eff) = 5940 K and log g = 4. The values of the excitation temperatures for Ti, Cr, Mn, and Fe were calculated and found to be very close to each other. The abundances of the elements were obtained by the growth curve method and found to be normal.

Cutaneous beta human papillomaviruses and the development of male external genital lesions: A case-control study nested within the HIM Study.

PubMed

Pierce Campbell, Christine M; Gheit, Tarik; Tommasino, Massimo; Lin, Hui-Yi; Torres, B Nelson; Messina, Jane L; Stoler, Mark H; Rollison, Dana E; Sirak, Bradley A; Abrahamsen, Martha; Carvalho da Silva, Roberto J; Sichero, Laura; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

2016-10-01

Cutaneous human papillomaviruses (HPVs) increase the risk of non-melanoma skin cancer in sun-exposed skin. We examined the role of beta-HPV in the development of male external genital lesions (EGLs), a sun-unexposed site. In this nested case-control study (67 men with pathologically-confirmed EGLs and 134 controls), exfoliated cells collected from the surface of lesions and normal genital skin 0, 6, and 12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Beta-HPV prevalence was estimated and conditional logistic regression was used to evaluate the association with condyloma, the most common EGL. While beta-HPV prevalence among controls remained stable, the prevalence among cases was lowest on the surface of lesion. Detecting beta-HPV on the normal genital skin was not associated with the presence or development of condyloma. Cutaneous beta-HPV does not appear to be contributing to pathogenesis in male genital skin. Copyright © 2016. Published by Elsevier Inc.

Quantitative EEG in Children and Adults With Attention Deficit Hyperactivity Disorder: Comparison of Absolute and Relative Power Spectra and Theta/Beta Ratio.

PubMed

Markovska-Simoska, Silvana; Pop-Jordanova, Nada

2017-01-01

In recent decades, resting state electroencephalographic (EEG) measures have been widely used to document underlying neurophysiological dysfunction in attention deficit hyperactivity disorder (ADHD). Although most EEG studies focus on children, there is a growing interest in adults with ADHD too. The aim of this study was to objectively assess and compare the absolute and relative EEG power as well as the theta/beta ratio in children and adults with ADHD. The evaluated sample comprised 30 male children and 30 male adults with ADHD diagnosed according to DSM-IV criteria. They were compared with 30 boys and 30 male adults matched by age. The mean age (±SD) of the children's group was 9 (±2.44) years and the adult group 35.8 (±8.65) years. EEG was recorded during an eyes-open condition. Spectral analysis of absolute (μV 2 ) and relative power (%) was carried out for 4 frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-21 Hz). The findings obtained for ADHD children are increased absolute power of slow waves (theta and delta), whereas adults exhibited no differences compared with normal subjects. For the relative power spectra there were no differences between the ADHD and control groups. Across groups, the children showed greater relative power than the adults in the delta and theta bands, but for the higher frequency bands (alpha and beta) the adults showed more relative power than children. Only ADHD children showed greater theta/beta ratio compared to the normal group. Classification analysis showed that ADHD children could be differentiated from the control group by the absolute theta values and theta/beta ratio at Cz, but this was not the case with ADHD adults. The question that should be further explored is if these differences are mainly due to maturation processes or if there is a core difference in cortical arousal between ADHD children and adults. © EEG and Clinical Neuroscience Society (ECNS) 2016.

The quantified EEG characteristics of responders and non-responders to long-term treatment with atomoxetine in children with attention deficit hyperactivity disorders.

PubMed

Chiarenza, Giuseppe Augusto; Chabot, Robert; Isenhart, Robert; Montaldi, Luciano; Chiarenza, Marco Paolo; Torto, Maria Grazia Lo; Prichep, Leslie S

2016-06-01

The aim of our study is to examine quantitative Electroencephalogram (QEEG) differences between ADHD patients that are responders and non-responders to long-term treatment with Atomoxetine at baseline and after 6 and 12months of treatment. Patients with attention deficit hyperactivity disorder (ADHD) received atomoxetine titrated, over 7days, from 0.5 to 1.2mg/kg/day. QEEG and Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV) scores were recorded before treatment and after therapy. Twenty minutes of eyes closed resting EEG was recorded from 19 electrodes referenced to linked earlobes. Full frequency and narrow band spectra of two minutes of artifact-free EEG were computed as well as source localization using Variable Resolution Electrical Tomography (VARETA). Abnormalities were identified using Z-spectra relative to normative values. Patients were classified as responders, non-responders and partial responders based upon the SNAP-IV findings. At baseline, the responders showed increased absolute power in alpha and delta in frontal and temporal regions, whereas, non-responders showed increased absolute power in all frequency bands that was widely distributed. With treatment responders' absolute power values moved toward normal values, whereas, non-responders remained at baseline values. Patients with increased power in the alpha band with no evidence of alterations in the beta or theta range, might be responders to treatment with atomoxetine. Increased power in the beta band coupled with increased alpha seems to be related to non-responders and one should consider atomoxetine withdrawal, especially if there is persistence of increased alpha and beta accompanied by an increase of theta. Copyright © 2016 Elsevier B.V. All rights reserved.

Financial market dynamics: superdiffusive or not?

NASA Astrophysics Data System (ADS)

Devi, Sandhya

2017-08-01

The behavior of stock market returns over a period of 1-60 d has been investigated for S&P 500 and Nasdaq within the framework of nonextensive Tsallis statistics. Even for such long terms, the distributions of the returns are non-Gaussian. They have fat tails indicating that the stock returns do not follow a random walk model. In this work, a good fit to a Tsallis q-Gaussian distribution is obtained for the distributions of all the returns using the method of Maximum Likelihood Estimate. For all the regions of data considered, the values of the scaling parameter q, estimated from 1 d returns, lie in the range 1.4-1.65. The estimated inverse mean square deviations (beta) show a power law behavior in time with exponent values between  -0.91 and  -1.1 indicating normal to mildly subdiffusive behavior. Quite often, the dynamics of market return distributions is modelled by a Fokker-Plank (FP) equation either with a linear drift and a nonlinear diffusion term or with just a nonlinear diffusion term. Both of these cases support a q-Gaussian distribution as a solution. The distributions obtained from current estimated parameters are compared with the solutions of the FP equations. For negligible drift term, the inverse mean square deviations (betaFP) from the FP model follow a power law with exponent values between  -1.25 and  -1.48 indicating superdiffusion. When the drift term is non-negligible, the corresponding betaFP do not follow a power law and become stationary after certain characteristic times that depend on the values of the drift parameter and q. Neither of these behaviors is supported by the results of the empirical fit.

Adenoviral receptor expression of normal bladder and transitional cell carcinoma of the bladder.

PubMed

Buscarini, Maurizio; Quek, Marcus L; Gilliam-Hegarich, Susan; Kasahara, Nori; Bochner, Bernard

2007-01-01

The insertion of absent or underexpressed genes into cancer cells to alter their malignant phenotype is an important potential application of available gene therapy technology. One of the more common viral vector systems that has been extensively studied for this purpose are the replication-deficient adenoviruses (Ad). Adenoviral infection of cells is mediated through a complex pathway, initiated following viral-cell attachment. Adenoviral-cell attachment occurs following interactions with a 46-kDa transmembrane protein with high affinity for both the Coxsackie and adenovirus, designated the CAR (Coxsackie and adenoviral receptor). Additional important cell-viral interactions that occur involve the alpha(v)-based integrins, specifically alpha(v)beta3 and alpha(v)beta5. The purpose of the present study was to determine the extent of expression and localization of the known Ad receptor proteins (CAR, alpha(v)beta3, and alpha(v)beta5) in normal and cancerous human bladders. Frozen tissue samples of normal bladder and invasive transitional cell cancers of the bladder were evaluated. Tissue blocks containing muscle-invasive transitional cell carcinoma (TCC) were obtained following radical cystectomy, which were performed at our institution. Thirty-two invasive transitional cell bladder tumors were evaluated, each with a matched sample of histologically normal-appearing bladder used as a control. Four additional samples of normal bladder were obtained from patients with no evidence of disease of the bladder and served as further controls. Three additional cases of invasive bladder cancer with no matching normal tissue were also evaluated. Identification of the CAR receptor was performed using the anti-CAR mouse monoclonal antibody designated RmBC. The integrins alpha(v)beta3 and alpha(v)beta5 were identified using the mouse monoclonal antibodies designated LM609 and P1F6 respectively. All slides were evaluated by two of the authors (M.B., B.B.) without knowledge of the clinical and pathological data. Normal bladder: Normal bladder mucosa demonstrated a marked positivity for CAR in 29/35 (82.8%) cases. In contrast, normal transitional epithelial cells were uniformly negative when tested for the integrins alpha(v)beta3 and alpha(v)beta5. Subepithelial tissues, specifically the connective tissue components of the lamina propria and deep muscle wall of the bladder, were positive for alpha(v)beta3 and for alpha(v)beta5 in 61 and 75% of samples, respectively. Endothelial cells associated with the various layers throughout the bladder uniformly expressed both integrins and served as a consistent internal control for both antibodies. An almost identical staining pattern of the endothelium was observed using LM609 and P1F6 in all samples tested. Bladder transitional cell carcinoma: CAR immunoreactivity against TCC cells was uniformly decreased compared to normal transitional cells. Nine tumors exhibited a weak positivity for CAR while the remaining samples were negative. In some cases, the absence of CAR positivity was associated with histological evidence of carcinoma in situ. In 6 cases, it led to the identification of small regions of carcinoma in situ that were not noted on primary pathological evaluation. Peritumoral connective tissue expressed both integrins in the majority of cases, similar to the pattern described above for normal bladder. Transitional cell cancers demonstrated a similar pattern of expression of alpha(v)beta5, in which all tumor cells exhibited minimal or no staining. The success of all viral-mediated gene therapy strategies relies on the ability of the vector to efficiently deliver its genetic material to a target cell population. In the current study, we demonstrate that the bladder epithelial layer consistently expresses high levels of CAR. Deeper layers of the epithelium also express CAR, including the basal layer cells. A decrease in the expression of CAR appears as an early event in bladder carcinogenesis. We observed that both alpha(v)beta3 and alpha(v)beta5 are strongly expressed in muscle cells surrounding the neoplastic cells, as well as within the peritumoral connective tissue. In cases of invasive bladder cancer that have lost CAR expression, an adenoviral vector may still be utilized through the less efficient interactions with the integrins. Bladder tumor tissue may be less susceptible to an adenoviral-mediated gene therapy approach in which a significant percentage of tumor cells require transduction. Adenoviral uptake by tumor or peritumoral cells with subsequent gene transfer could be predicted by the level of CAR and alpha(v)-based integrin expression. This would enhance our ability to identify those patients whose tumors would be more susceptible to Ad-mediated gene delivery as part of an antitumor treatment. 2007 S. Karger AG, Basel

Effect of diet on oxidation of 17 beta-estradiol in vivo.

PubMed

Musey, P I; Collins, D C; Bradlow, H L; Gould, K G; Preedy, J R

1987-10-01

The effect of a high fat, low carbohydrate, low protein diet on the in vivo oxidation of 17 beta-estradiol was studied using radiometric methods. Five male chimpanzees were fed a normal (13%) fat diet or a high (65%) fat diet for 8 weeks. After a 4-week rest period, the animals were fed the alternative diet. The mean percent oxidation of 16 alpha-[3H]estradiol-17 beta 24 h after injection was 3.8 +/- 1.3% (+/- SD) on the normal diet vs. 18.4 +/- 4.7% on the high fat diet (P less than 0.01). In contrast, the mean percent oxidation of 2-[3H]estradiol 24 h after injection was 31.6 +/- 3.8% (+/- SD) on the normal diet vs. 20.0 +/- 3.5% on the high fat diet (P less than 0.05). These results suggest that the oxidation of 17 beta-estradiol to estriols relative to that to catechol estrogens is increased by a high fat diet.

Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue.

PubMed Central

Nagle, R. B.; Hao, J.; Knox, J. D.; Dalkin, B. L.; Clark, V.; Cress, A. E.

1995-01-01

The progression of prostate carcinoma may be influenced by the biochemical nature of the basal lamina surrounding the primary carcinoma cells. As a first step toward understanding this process, the composition and structure of the basal lamina in normal prostate, prostatic intraepithelial neoplasia, and human carcinoma were determined. In addition, a comparison was made between the attachments of the normal basal cell to its underlying basal lamina and those made by primary prostate carcinoma. The normal basal cells form both focal adhesions and hemidesmosomal-like structures as observed by transmission electron microscopy. The normal basal cells exhibited a polarized distribution of hemidesmosomal associated proteins including BP180, BP230, HD1, plectin, laminin-gamma 2(B2t), collagen VII, and the corresponding integrin laminin receptors alpha 6 beta 1 and alpha 6 beta 4. The expression and distribution pattern of these proteins were retained in the prostate intraepithelial neoplasia lesions. In contrast, the carcinoma cells uniformly lacked hemidesmosomal structures, the integrin alpha 6 beta 4, BP180, laminin-gamma 2 (B2t), and collagen VII but did express BP230 (30%), plectin, HD1 (15%), and the integrin laminin receptors alpha 3 beta 1 and alpha 6 beta 1. These results suggest that, although a detectable basal lamina structure is present in carcinoma, its composition and cellular attachments are abnormal. The loss of critical cellular attachments may play a role in influencing the progression potential of prostate carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7778688

Ultraviolet and optical spectrophotometry of the Seyfert 1.8 galaxy Markarian 609

NASA Technical Reports Server (NTRS)

Rudy, Richard J.; Cohen, Ross D.; Ake, T. B.

1988-01-01

Ultraviolet and optical observations of the Seyfert 1.8 galaxy Mrk 609 were collected simultaneously. The observations reveal strong line and continuum emission in the UV, an increase in the flux of H-beta and He I 5876, and a decrease in the H-alpha/H-beta value since the measurements by Osterbrock (1978, 1981), as well as an extended population of early-type stars, which is considered to be the source powering the larger part of the far-IR emission. Special attention is given to the origin of steep broad-line Balmer decrement measured by Osterbrock, since the strong UV continuum and the emission lines of Mrk 609 observed rule out reddening as the cause of the Balmer decrement. It is suggested that smaller-than-normal optical depths are likely to be the cause of the decrement.

Differential regulation of amyloid-. beta. -protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, G.A.; Lewis, D.A.; Bahmanyar, S.

1988-02-01

The authors have mapped the neuroanatomical distribution of amyloid-..beta..-protein mRNA within neuronal subpopulations of the hippocampal formation in the cynomolgus monkey (Macaca fascicularis), normal aged human, and patients with Alzheimer disease. Amyloid-..beta..-protein mRNA appears to be expressed in all hippocampal neurons, but at different levels of abundance. In the central nervous system of monkey and normal aged human, image analysis shows that neurons of the dentate gyrus and cornu Ammonis fields contain a 2.5-times-greater hybridization signal than is present in neurons of the subiculum and entorhinal cortex. In contrast, in the Alzheimer disease hippocampal formation, the levels of amyloid-..beta..-protein mRNAmore » in the cornu Ammonis field 3 and parasubiculum are equivalent. These findings suggest that within certain neuronal subpopulations cell type-specific regulation of amyloid-..beta..-protein gene expression may be altered in Alzheimer disease.« less

The contribution of light Majorana neutrinos to neutrinoless double beta decay and cosmology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dell'Oro, S.; Marcocci, S.; Viel, M.

Cosmology is making impressive progress and it is producing stringent bounds on the sum of the neutrino masses Σ, a parameter of great importance for the current laboratory experiments. In this letter, we exploit the potential relevance of the analysis of Palanque-Delabrouille et al. [JCAP 02 (2015) 045] to the neutrinoless double beta decay (0ν β β) search. This analysis indicates small values for the lightest neutrino mass, since the authors find Σ < 84 meV at 1σ C.L., and provides a 1σ preference for the normal hierarchy. The allowed values for the Majorana effective mass, probed by 0ν β β, turn out to be < 75more » meV at 3σ C.L. and lower down to less than 02 meV at 1σ C.L. . If this indication is confirmed, the impact on the 0ν β β experiments will be tremendous since the possibility of detecting a signal will be out of the reach of the next generation of experiments.« less

The contribution of light Majorana neutrinos to neutrinoless double beta decay and cosmology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dell’Oro, S.; Marcocci, S.; Viel, M.

Cosmology is making impressive progress and it is producing stringent bounds on the sum of the neutrino masses Σ, a parameter of great importance for the current laboratory experiments. In this letter, we exploit the potential relevance of the analysis of Palanque-Delabrouille et al. to the neutrinoless double beta decay (0νββ) search. This analysis indicates small values for the lightest neutrino mass, since the authors find Σ<84 meV at 1σ C.L., and provides a 1σ preference for the normal hierarchy. The allowed values for the Majorana effective mass, probed by 0νββ, turn out to be <75 meV at 3σ C.L.more » and lower down to less than 20 meV at 1σ C.L. . If this indication is confirmed, the impact on the 0νββ experiments will be tremendous since the possibility of detecting a signal will be out of the reach of the next generation of experiments.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

Oak Ridge Associated Universities (ORAU), under the Oak Ridge Institute for Science and Education (ORISE) contract, collected split surface water samples with Nuclear Fuel Services (NFS) representatives on March 20, 2013. Representatives from the U.S. Nuclear Regulatory Commission and the Tennessee Department of Environment and Conservation were also in attendance. Samples were collected at four surface water stations, as required in the approved Request for Technical Assistance number 11-018. These stations included Nolichucky River upstream (NRU), Nolichucky River downstream (NRD), Martin Creek upstream (MCU), and Martin Creek downstream (MCD). Both ORAU and NFS performed gross alpha and gross beta analyses,more » and Table 1 presents the comparison of results using the duplicate error ratio (DER), also known as the normalized absolute difference. A DER {<=} 3 indicates that at a 99% confidence interval, split sample results do not differ significantly when compared to their respective one standard deviation (sigma) uncertainty (ANSI N42.22). The NFS split sample report does not specify the confidence level of reported uncertainties (NFS 2013). Therefore, standard two sigma reporting is assumed and uncertainty values were divided by 1.96. In conclusion, most DER values were less than 3 and results are consistent with low (e.g., background) concentrations. The gross beta result for sample 5198W0012 was the exception. The ORAU result of 9.23 ± 0.73 pCi/L from location MCD is well above NFS's result of -0.567 ± 0.63 pCi/L (non-detected). NFS's data package included a detected result for U-233/234, but no other uranium or plutonium detection, and nothing that would suggest the presence of beta-emitting radionuclides. The ORAU laboratory reanalyzed sample 5198W0012 using the remaining portion of the sample volume and a result of 11.3 ± 1.1 pCi/L was determined. As directed, the laboratory also counted the filtrate using gamma spectrometry analysis and identified only naturally occurring or ubiquitous man-made constituents, including beta emitters that are presumably responsible for the elevated gross beta values.« less

Advanced ECCD based NTM control in closed-loop operation at ASDEX Upgrade (AUG)

NASA Astrophysics Data System (ADS)

Reich, Matthias; Barrera-Orte, Laura; Behler, Karl; Bock, Alexander; Giannone, Louis; Maraschek, Marc; Poli, Emanuele; Rapson, Chris; Stober, Jörg; Treutterer, Wolfgang

2012-10-01

In high performance plasmas, Neoclassical Tearing Modes (NTMs) are regularly observed at reactor-grade beta-values. They limit the achievable normalized beta, which is undesirable because fusion performance scales as beta squared. The method of choice for controlling and avoiding NTMs at AUG is the deposition of ECCD inside the magnetic island for stabilization in real-time (rt). Our approach to tackling such complex control problems using real-time diagnostics allows rigorous optimization of all subsystems. Recent progress in rt-equilibrium reconstruction (< 3.5 ms), rt-localization of NTMs (< 8 ms) and rt beam tracing (< 25 ms) allows closed-loop feedback operation using multiple movable mirrors as the ECCD deposition actuator. The rt-equilibrium uses function parametrization or a fast Grad-Shafranov solver with an option to include rt-MSE measurements. The island localization is based on a correlation of ECE and filtered Mirnov signals. The rt beam-tracing module provides deposition locations and their derivative versus actuator position of multiple gyrotrons. The ``MHD controller'' finally drives the actuators. Results utilizing closed-loop operation with multiple gyrotrons and their effect on NTMs are shown.

Genetic basis of human complement C8[beta] deficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaufmann, T.; Rittner, C.; Schneider, P.M.

1993-06-01

The eighth component of human complement (c8) is a serum protein consisting of three chains ([alpha], [beta], and [gamma]) and encoded by three different genes, C8A, C8B, and C8G. C8A and C8B are closely linked on chromosome 1p, whereas C8G is located on chromosome 9q. In the serum the [beta] subunit is non-covalently bound to the disulfide-linked [alpha]-[gamma] subunit. Patients with C8[beta] deficiency suffer from recurrent neisserial infections such as meningitis. Exon-specific polymerase chain reaction (PCR) amplification with primer pairs from the flanking intron sequences was used to amplify all 12 C8B exons separately. No difference regarding the exon sizesmore » was observed in a C8[beta]-deficient patient compared with a normal person. Therefore, direct sequence analysis of all exon-specific PCR products from normal and C8[beta]-deficient individuals was carried out. As a cause for C8[beta] deficiency, we found a single C-T exchange in exon 9 leading to a stop codon. An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the Taql polymorphism located in intron 11, five families with 7 C8[beta]-deficient members were investigated. The mutation was not found to be restricted to one of the two Taql RFLP alleles. The mutant allele was observed in all families investigated and can therefore be regarded as a major cause of C8[beta] deficiency in the Caucasian population. In addition, two C8[beta]-deficient patients were found to be heterozygous for the C-T exchange. The molecular basis of the alleles without this point mutation also causing deficiency has not yet been defined. 23 refs., 4 figs., 3 tabs.« less

Phospholipase C-beta4 is essential for the progression of the normal sleep sequence and ultradian body temperature rhythms in mice.

PubMed

Ikeda, Masayuki; Hirono, Moritoshi; Sugiyama, Takashi; Moriya, Takahiro; Ikeda-Sagara, Masami; Eguchi, Naomi; Urade, Yoshihiro; Yoshioka, Tohru

2009-11-09

THE SLEEP SEQUENCE: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the beta4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-beta4-deficient mutant (PLC-beta4-/-) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-beta4-/- mice, however. Therefore, we analyzed 24-h sleep electroencephalogram in PLC-beta4-/- mice. PLC-beta4-/- mice exhibited normal non-REM sleep both during the day and nighttime. PLC-beta4-/- mice, however, exhibited increased REM sleep during the night, their active period. Also, their sleep was fragmented with unusual wake-to-REM sleep transitions, both during the day and nighttime. In addition, PLC-beta4-/- mice reduced ultradian body temperature rhythms and elevated body temperatures during the daytime, but had normal homeothermal response to acute shifts in ambient temperatures (22 degrees C-4 degrees C). Within the most likely brain areas to produce these behavioral phenotypes, we found that, not orexin, but group-1 metabotropic glutamate receptor (mGluR)-mediated Ca(2+) mobilization was significantly reduced in the dorsal lateral geniculate nucleus (LGNd) of PLC-beta4-/- mice. Voltage clamp recordings revealed that group-1 mGluR-mediated currents in LGNd relay neurons (inward in wild-type mice) were outward in PLC-beta4-/- mice. These lines of evidence indicate that impaired LGNd relay, possibly mediated via group-1 mGluR, may underlie irregular sleep sequences and ultradian body temperature rhythms in PLC-beta4-/- mice.

Pittsburgh Compound B and AV-1451 positron emission tomography assessment of molecular pathologies of Alzheimer's disease in progressive supranuclear palsy.

PubMed

Whitwell, Jennifer L; Ahlskog, J Eric; Tosakulwong, Nirubol; Senjem, Matthew L; Spychalla, Anthony J; Petersen, Ronald C; Jack, Clifford R; Lowe, Val J; Josephs, Keith A

2018-03-01

Little is known about Alzheimer's disease molecular proteins, beta-amyloid and paired helical filament (PHF) tau, in progressive supranuclear palsy (PSP). Recent techniques have been developed to allow for investigations of these proteins in PSP. We determined the frequency of beta-amyloid deposition in PSP, and whether beta-amyloid deposition in PSP is associated with PHF-tau deposition pattern, or clinical features. Thirty probable PSP participants underwent MRI, [ 18 F]AV-1451 PET and Pittsburgh compound B (PiB) PET. Apolipoprotein (APOE) genotyping was also performed. A global PiB standard-uptake value ratio (SUVR) was calculated. AV-1451 SUVRs were calculated for a set of Alzheimer's disease (AD)-related regions and a set of PSP-related regions. Voxel-level analyses were conducted to assess for differences in AV-1451 uptake patterns and MRI atrophy between PiB(+) and PiB(-) cases compared to 60 normal PiB(-) controls. Statistical testing for correlations and associations between variables of interest were also performed. Twelve subjects (40%) showed beta-amyloid deposition. Higher PiB SUVR correlated with older age but not with AV-1451 SUVR in the AD- or PSP-related regions. Higher AV-1451 SUVR in AD-related regions was associated with higher AV-1451 SUVR in PSP-related regions. We found little evidence for beta-amyloid related differences in clinical metrics, proportion of APOE e4 carriers, pattern of AV-1451 uptake, or pattern of atrophy. Beta-amyloid deposition occurs in a relatively high proportion of PSP subjects. Unlike in Alzheimer's disease, however, there is little evidence that beta-amyloid, and PHF-tau, play a significant role in neurodegeneration in PSP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and beta2-agonist use.

PubMed

Hastie, Annette T; Wu, Min; Foster, Gayle C; Hawkins, Gregory A; Batra, Vikas; Rybinski, Katherine A; Cirelli, Rosemary; Zangrilli, James G; Peters, Stephen P

2006-02-15

Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo beta2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for beta2-adrenergic receptor haplotype determination. Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the beta2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to beta-agonist. The decreased phosphorylation does not appear to be associated with a particular beta2-adrenergic receptor haplotype. The observed decrease in VASP phosphorylation suggests greater inhibition of actin reorganization which is necessary for altering attachment and migration required during epithelial repair.

Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers.

PubMed

Zhang, S; Zhang, H S; Reuter, V E; Slovin, S F; Scher, H I; Livingston, P O

1998-02-01

Defining the expression of tumor-associated antigens on primary and metastatic prostate cancer is the crucial first step in selecting appropriate targets for immune attack. In this study, the distribution of the tumor-associated antigens GM2, Tn, sTn, Thompson-Friedenreich antigen (TF), Globo H, Le(y), MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC7, carcinoembryonic antigen, beta chain of human chorionic gonadotropin (hCG beta), HER2/neu, PSMA, and KSA on primary and metastatic prostate cancer and 16 types of normal tissues was compared by immunohistochemistry, using a panel of well-characterized monoclonal antibodies. Our results show that GM2, KSA, and MUC2 were strongly expressed on 8 or 9 of 9 metastatic prostate cancer biopsy specimens and, with PSMA, hCG beta, TF, Tn, and sTn, on 8 or more of 11 primary prostate cancer specimens. Tn, MUC1, and PSMA were expressed on 4-6 of 9 metastatic specimens. The remaining antigens were expressed on no more than three of nine metastatic specimens. Normal tissues were also tested with all antibodies. With regard to the eight antigens most widely expressed on prostate cancers, PSMA was not expressed significantly on any of the normal tissues except prostate epithelium. Tn, sTn, hCG beta, and MUC2 were detected on up to 3 of 10 types of normal epithelia. GM2, TF, MUC1, and KSA were more broadly distributed on normal epithelia, all primarily at the secretory borders. STn, KSA, and hCG beta were also detected in the testis, and GM2 was expressed on gray matter of brain. From the 30 antigens that we have screened, this study provides the basis for selecting GM2, TF, Tn, sTn, hCG beta, MUC1, MUC2, KSA, and PSMA as target antigens for specific immunotherapy of prostate cancer.

Gray matter network disruptions and amyloid beta in cognitively normal adults.

PubMed

Tijms, Betty M; Kate, Mara Ten; Wink, Alle Meije; Visser, Pieter Jelle; Ecay, Mirian; Clerigue, Montserrat; Estanga, Ainara; Garcia Sebastian, Maite; Izagirre, Andrea; Villanua, Jorge; Martinez Lage, Pablo; van der Flier, Wiesje M; Scheltens, Philip; Sanz Arigita, Ernesto; Barkhof, Frederik

2016-01-01

Gray matter networks are disrupted in Alzheimer's disease (AD). It is unclear when these disruptions start during the development of AD. Amyloid beta 1-42 (Aβ42) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between Aβ42 levels in cerebrospinal fluid (CSF) and single-subject cortical gray matter network measures. Single-subject gray matter networks were extracted from structural magnetic resonance imaging scans in a sample of cognitively healthy adults (N = 185; age range 39-79, mini-mental state examination >25, N = 12 showed abnormal Aβ42 < 550 pg/mL). Degree, clustering coefficient, and path length were computed at whole brain level and for 90 anatomical areas. Associations between continuous Aβ42 CSF levels and single-subject cortical gray matter network measures were tested. Smoothing splines were used to determine whether a linear or nonlinear relationship gave a better fit to the data. Lower Aβ42 CSF levels were linearly associated at whole brain level with lower connectivity density, and nonlinearly with lower clustering values and higher path length values, which is indicative of a less-efficient network organization. These relationships were specific to medial temporal areas, precuneus, and the middle frontal gyrus (all p < 0.05). These results suggest that mostly within the normal spectrum of amyloid, lower Aβ42 levels can be related to gray matter networks disruptions. Copyright © 2016 Elsevier Inc. All rights reserved.

Penning trap mass spectrometry Q-value determinations for highly forbidden β-decays

NASA Astrophysics Data System (ADS)

Sandler, Rachel; Bollen, Georg; Eibach, Martin; Gamage, Nadeesha; Gulyuz, Kerim; Hamaker, Alec; Izzo, Chris; Kandegedara, Rathnayake; Redshaw, Matt; Ringle, Ryan; Valverde, Adrian; Yandow, Isaac; Low Energy Beam Ion Trap Team

2017-09-01

Over the last several decades, extremely sensitive, ultra-low background beta and gamma detection techniques have been developed. These techniques have enabled the observation of very rare processes, such as highly forbidden beta decays e.g. of 113Cd, 50V and 138La. Half-life measurements of highly forbidden beta decays provide a testing ground for theoretical nuclear models, and the comparison of calculated and measured energy spectra could enable a determination of the values of the weak coupling constants. Precision Q-value measurements also allow for systematic tests of the beta-particle detection techniques. We will present the results and current status of Q value determinations for highly forbidden beta decays. The Q values, the mass difference between parent and daughter nuclides, are measured using the high precision Penning trap mass spectrometer LEBIT at the National Superconducting Cyclotron Laboratory.

IL1{beta}-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Yingting, E-mail: yitizhu@yahoo.com; Tissue Tech Inc, Miami, FL 33173; Zhu, Min

2012-11-15

COX-2 is a major inflammatory mediator implicated in colorectal inflammation and cancer. However, the exact origin and role of COX-2 on colorectal inflammation and carcinogenesis are still not well defined. Recently, we reported that COX-2 and iNOS signalings interact in colonic CCD18Co fibroblasts. In this article, we investigated whether activation of COX-2 signaling by IL1{beta} in primary colonic fibroblasts obtained from normal and cancer patients play a critical role in regulation of proliferation and invasiveness of human colonic epithelial cancer cells. Our results demonstrated that COX-2 level was significantly higher in cancer associated fibroblasts than that in normal fibroblasts withmore » or without stimulation of IL-1{beta}, a powerful stimulator of COX-2. Using in vitro assays for estimating proliferative and invasive potential, we discovered that the proliferation and invasiveness of the epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts than with normal fibroblasts, with or without stimulation of IL1{beta}. Further analysis indicated that the major COX-2 product, prostaglandin E{sub 2}, directly enhanced proliferation and invasiveness of the epithelial cancer cells in the absence of fibroblasts. Moreover, a selective COX-2 inhibitor, NS-398, blocked the proliferative and invasive effect of both normal and cancer associate fibroblasts on the epithelial cancer cells, with or without stimulation of IL-1{beta}. Those results indicate that activation of COX-2 signaling in the fibroblasts plays a major role in promoting proliferation and invasiveness of the epithelial cancer cells. In this process, PKC is involved in the activation of COX-2 signaling induced by IL-1{beta} in the fibroblasts.« less

A sensitive and reproducible fluorescent-based HPLC assay to measure the activity of acid as well as neutral beta-glucocerebrosidases.

PubMed

Hayashi, Yasuhiro; Zama, Kouta; Abe, Eriko; Okino, Nozomu; Inoue, Takehiko; Ohno, Kousaku; Ito, Makoto

2008-12-01

The activity of lysosomal acid beta-glucocerebrosidase (AGC, EC 3.2.1.45), which hydrolyzes the O-glycosidic linkage between D-glucose and ceramide of glucosylceramide (GlcCer), is a marker for the diagnosis of Gaucher disease because the disease is caused by dysfunction of AGC due to mutations in the gene. The activity of AGC is potently inhibited by conduritol B epoxide (CBE), whereas CBE-insensitive nonlysosomal neutral beta-glucocerebrosidase (NGC) activities have been found in various vertebrates, including humans. We report here a new reliable method to determine AGC as well as NGC activities using normal-phase high-performance liquid chromatography (HPLC) and NBD (4-nitrobenzo-2-oxa-1,3-diazole)- or BODIPY (4,4-difluoro-4-boro-3a,4a-diaza-s-indacene)-labeled GlcCer as a substrate. The reaction products of the enzymes, C6-NBD-ceramide and C12-BODIPY-ceramide, were clearly separated from the corresponding substrates on a normal-phase column within 5 min using a different solvent system. Reaction products could be detected quantitatively at concentrations ranging from 50 fmol to 50 pmol for C6-NBD-ceramide and from 10 fmol to 5 pmol for C12-BODIPY-ceramide. V(max)/K(m) values of human fibroblast AGC for fluorescent GlcCer were much higher than those for 4-methylumbelliferyl-beta-d-glucoside (4MU-Glc), which is used prevalently for Gaucher disease diagnosis. As a result, AGC activity was detected quantitatively using fluorescent GlcCer, but not 4MU-Glc, using 5 microl of human serum or 1 x 10(4) cultured human fibroblasts. The current method clearly showed the decrease of AGC activities in fibroblasts and serum from the patient with Gaucher disease compared with normal individuals, suggesting that the method is applicable for the diagnosis of Gaucher disease. Furthermore, this method was found to be useful for measuring the activities of nonlysosomal NGC of various cells and tissues in the presence of CBE.

Improvement of macrophage dysfunction by administration of anti-transforming growth factor-beta antibody in EL4-bearing hosts.

PubMed

Maeda, H; Tsuru, S; Shiraishi, A

1994-11-01

An experimental therapy for improvement of macrophage dysfunction caused by transforming growth factor-beta (TGF-beta) was tried in EL4 tumor-bearing mice. TGF-beta was detected in cell-free ascitic fluid from EL4-bearers, but not in that from normal mice, by western blot analysis. The ascites also showed growth-suppressive activity against Mv1Lu cells, and the suppressive activity was potentiated by transient acidification. To investigate whether the functions of peritoneal macrophages were suppressed in EL4-bearers, the abilities to produce nitric oxide and tumor necrosis factor-alpha (TNF-alpha) upon lipopolysaccharide (LPS) stimulation were measured. Both abilities of macrophages in EL4-bearing mice were suppressed remarkably on day 9, and decreased further by day 14, compared with non-tumor-bearing controls. TGF-beta activity was abrogated by administration of anti-TGF-beta antibody to EL4-bearing mice. While a large amount of TGF-beta was detected in ascitic fluid from control EL4-bearers, little TGF-beta was detectable in ascites from EL4-bearers given anti-TGF-beta antibody. Furthermore, while control macrophages exhibited little or no production of nitric oxide and TNF-alpha on LPS stimulation in vitro, macrophages from EL4-bearers administered with anti-TGF-beta antibody showed the same ability as normal macrophages. These results clearly indicate that TGF-beta contributes to macrophage dysfunction and that the administration of specific antibody for TGF-beta reverses macrophage dysfunction in EL4-bearing hosts.

ALK and TGF-Beta Resistance in Breast Cancer

DTIC Science & Technology

2017-10-01

and H.F. Lodish, Role of transforming growth factor beta in human disease. N Engl J Med, 2000. 342(18): p. 1350-8. 3. Massague, J., S.W. Blain, and... Transforming growth factor-beta signaling in normal and malignant hematopoiesis. Leukemia, 2003. 17(9): p. 1731-7. 5. Lehman, H.L., et al., Modeling and

REM Sleep EEG Instability in REM Sleep Behavior Disorder and Clonazepam Effects.

PubMed

Ferri, Raffaele; Rundo, Francesco; Silvani, Alessandro; Zucconi, Marco; Bruni, Oliviero; Ferini-Strambi, Luigi; Plazzi, Giuseppe; Manconi, Mauro

2017-08-01

We aimed to analyze quantitatively rapid eye movement (REM) sleep electroencephalogram (EEG) in controls, drug-naïve idiopathic REM sleep behavior disorder patients (iRBD), and iRBD patients treated with clonazepam. Twenty-nine drug-naïve iRBD patients (mean age 68.2 years), 14 iRBD patients under chronic clonazepam therapy (mean age 66.3 years), and 21 controls (mean age 66.8 years) were recruited. Power spectra were obtained from sleep EEG (central derivation), using a 2-second sliding window, with 1-second steps. The power values of each REM sleep EEG spectral band (one every second) were normalized with respect to the average power value obtained during sleep stage 2 in the same individual. In drug-naïve patients, the normalized power values showed a less pronounced REM-related decrease of power in all bands with frequency <15 Hz than controls and an increase in the beta band, negatively correlated with muscle atonia; in patients treated with clonazepam there was a partial return of all bands <15 Hz toward the control values. The standard deviation values of the normalized power were higher for untreated patients in all EEG bands and were almost completely normalized in patients treated with clonazepam. The REM sleep EEG structure changes found in this study disclose subtle but significant alterations in the cortical electrophysiology of RBD that might represent the early expression of the supposed neurodegenerative processes already taking place at this stage of the disease and might be the target of better and effective future therapeutic strategies for this condition. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Kinetic effects on Alfven wave nonlinearity. II - The modified nonlinear wave equation

NASA Technical Reports Server (NTRS)

Spangler, Steven R.

1990-01-01

A previously developed Vlasov theory is used here to study the role of resonant particle and other kinetic effects on Alfven wave nonlinearity. A hybrid fluid-Vlasov equation approach is used to obtain a modified version of the derivative nonlinear Schroedinger equation. The differences between a scalar model for the plasma pressure and a tensor model are discussed. The susceptibilty of the modified nonlinear wave equation to modulational instability is studied. The modulational instability normally associated with the derivative nonlinear Schroedinger equation will, under most circumstances, be restricted to left circularly polarized waves. The nonlocal term in the modified nonlinear wave equation engenders a new modulational instability that is independent of beta and the sense of circular polarization. This new instability may explain the occurrence of wave packet steepening for all values of the plasma beta in the vicinity of the earth's bow shock.

Estimating the age of Hb G-Coushatta [β22(B4)Glu→Ala] mutation by haplotypes of β-globin gene cluster in Denizli, Turkey.

PubMed

Ozturk, Onur; Arikan, Sanem; Atalay, Ayfer; Atalay, Erol O

2018-05-01

Hb G-Coushatta variant was reported from various populations' parts of the world such as Thai, Korea, Algeria, Thailand, China, Japan and Turkey. In our study, we aimed to discuss the possible historical relationships of the Hb G-Coushatta mutation with the possible migration routes of the world. For this purpose, associated haplotypes were determined using polymorphic loci in the beta globin gene cluster of hemoglobin G-Coushatta and normal populations in Denizli, Turkey. We performed statistical analysis such as haplotype analysis, Hardy-Weinberg equilibrium, measurement of genetic diversity and population differentiation parameters, analysis of molecular variance using F-statistics, historical-demographic analyses, mismatch distribution analysis of both populations and applied the test statistics in Arlequin ver. 3.5 software program. The diversity of haplotypes has been shown to indicate different genetic origins for two populations. However, AMOVA results, molecular diversity parameters and population demographic expansion times showed that the Hb G-Coushatta mutation develops on the normal population gene pool. Our estimated τ values showed the average time since the demographic expansion for normal and Hb G-Coushatta populations ranged from approximately 42,000 to 38,000 ybp, respectively. Our data suggest that Hb G-Coushatta population originate in normal population in Denizli, Turkey. These results support the hypothesis that the multiple origin of Hb G-Coushatta and indicate that mutation may have been triggered the formation of new variants on beta globin haplotypes. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Secondary metabolism in simulated microgravity: beta-lactam production by Streptomyces clavuligerus

NASA Technical Reports Server (NTRS)

Fang, A.; Pierson, D. L.; Mishra, S. K.; Koenig, D. W.; Demain, A. L.

1997-01-01

Rotating bioreactors designed at NASA's Johnson Space Center were used to simulate a microgravity environment in which to study secondary metabolism. The system examined was beta-lactam antibiotic production by Streptomyces clavuligerus. Both growth and beta-lactam production occurred in simulated microgravity. Stimulatory effects of phosphate and L-lysine, previously detected in normal gravity, also occurred in simulated microgravity. The degree of beta-lactam antibiotic production was markedly inhibited by simulated microgravity.

Treatment of prediabetes

PubMed Central

Kanat, Mustafa; DeFronzo, Ralph A; Abdul-Ghani, Muhammad A

2015-01-01

Progression of normal glucose tolerance (NGT) to overt diabetes is mediated by a transition state called impaired glucose tolerance (IGT). Beta cell dysfunction and insulin resistance are the main defects in type 2 diabetes mellitus (type 2 DM) and even normoglycemic IGT patients manifest these defects. Beta cell dysfunction and insulin resistance also contribute to the progression of IGT to type 2 DM. Improving insulin sensitivity and/or preserving functions of beta-cells can be a rational way to normalize the GT and to control transition of IGT to type 2 DM. Loosing weight, for example, improves whole body insulin sensitivity and preserves beta-cell function and its inhibitory effect on progression of IGT to type 2 DM had been proven. But interventions aiming weight loss usually not applicable in real life. Pharmacotherapy is another option to gain better insulin sensitivity and to maintain beta-cell function. In this review, two potential treatment options (lifestyle modification and pharmacologic agents) that limits the IGT-type 2 DM conversion in prediabetic subjects are discussed. PMID:26464759

Anomalous heat conduction and anomalous diffusion in nonlinear lattices, single walled nanotubes, and billiard gas channels.

PubMed

Li, Baowen; Wang, Jiao; Wang, Lei; Zhang, Gang

2005-03-01

We study anomalous heat conduction and anomalous diffusion in low-dimensional systems ranging from nonlinear lattices, single walled carbon nanotubes, to billiard gas channels. We find that in all discussed systems, the anomalous heat conductivity can be connected with the anomalous diffusion, namely, if energy diffusion is sigma(2)(t)=2Dt(alpha) (01) implies an anomalous heat conduction with a divergent thermal conductivity (beta>0), and more interestingly, a subdiffusion (alpha<1) implies an anomalous heat conduction with a convergent thermal conductivity (beta<0), consequently, the system is a thermal insulator in the thermodynamic limit. Existing numerical data support our theoretical prediction.

Cafeteria feeding induces interleukin-1beta mRNA expression in rat liver and brain.

PubMed

Hansen, M K; Taishi, P; Chen, Z; Krueger, J M

1998-06-01

intake affects gut-immune function and can provide a strong intestinal antigen challenge resulting in activation of host defense mechanisms in the digestive system. Previously, we showed that feeding rats a cafeteria diet increases non-rapid eye movement sleep by a subdiaphragmatic mechanism. Food intake and sleep regulation and the immune system share the regulatory molecule interleukin-1beta (IL-1beta). Thus this study examined the effects of a cafeteria diet on IL-1beta mRNA and IL-1 receptor accessory protein (IL-1RAP) mRNA expression in rat liver and brain. Rats were fed normal rat chow or a palatable diet consisting of bread, chocolate, and shortbread cookies (cafeteria diet). After 3 days, midway between the light period of the light-dark cycle, rats were killed by decapitation. Feeding rats a cafeteria diet resulted in increased IL-1beta mRNA expression in the liver and hypothalamus compared with rats fed only the normal rat chow. In addition, cafeteria feeding decreased IL-1RAP mRNA levels in the liver and brain stem. These results indicate that feeding has direct effects on cytokine production and together with other data suggest that the increased sleep that accompanies increased feeding may be the result of increased brain IL-1beta. These results further suggest that cytokine-to-brain communication may be important in normal physiological conditions, such as feeding, as well as being important during inflammatory responses.

Placental lactogen secretion during prolonged-pregnancy in the rat: the ovary plays a pivotal role in the control of placental function.

PubMed

Shiota, K; Furuyama, N; Takahashi, M

1991-10-01

The serum of rats at mid-pregnancy contains at least 2 distinct placental lactogen (PL)-like substances tentatively termed placental lactogen-alpha (PL-alpha) and placental lactogen-beta (PL-beta) (Endocrinol Japon 38: 533-540, 1991). We have investigated the secretory patterns of three placental lactogens (PL-alpha, PL-beta and placental lactogen-II) during normal pregnancy and in two prolonged-pregnancy models. Pregnancy was prolonged by the introduction of new corpora lutea by inducing ovulation on day 15 of pregnancy by successive treatments with PMSG (30 IU/rat, sc on day 12) and hCG (10 IU/rat, iv on day 14), and in the second model by progesterone implants on day 15 of pregnancy. During normal pregnancy, each of the 3 PLs exhibited only one secretory peak in the serum; PL-alpha and PL-beta on day 12 and placental lactogen II (PL-II) on day 20. Interestingly, in the rats with new sets of corpora lutea, serum PL-alpha and PL-beta levels began to increase again on day 18 and showed peaks on day 20 for PL-alpha and on day 22 for PL-beta. In this model, the initiation of PL-II secretion was not affected, but high levels were maintained until day 26, when parturition occurred. In rats receiving either PMSG or hCG, the secretory patterns of the PLs were similar to as those during normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta-cell function in former gestational diabetes.

PubMed

Tura, A; Mari, A; Prikoszovich, T; Pacini, G; Kautzky-Willer, A

2008-08-01

Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance. A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT. Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4.2 +/- 0.3 vs. 5.4 +/- 0.4 10(-4) min(-1) (microU/ml)(-1); OGTT: 440 +/- 7 vs. 472 +/- 9 ml min(-1) m(-2)). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 +/- 5 vs. 124 +/- 7 pmol min(-1) m(-2) mm(-1), P = 0.0407) and insulin secretion at 5 mm glucose (168 +/- 9 vs. 206 +/- 10 pmol min(-1) m(-2), P = 0.003). Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis.

Forbidden Mass Ranges for Shower Meteoroids

NASA Technical Reports Server (NTRS)

Moorhead, Althea V.

2017-01-01

Burns et al. (1979) use the parameter beta to describe the ratio of radiation pressure to gravity for a particle in the Solar System. The central potential that these particles experience is effectively reduced by a factor of (1- beta ), which in turn lowers the escape velocity. Burns et al. (1979) derived a simple expression for the value of beta at which particles ejected from a comet follow parabolic orbits and thus leave the Solar System; we expand on this to derive an expression for critical beta values that takes ejection velocity into account, assuming geometric optics. We use our expression to compute the critical value and corresponding mass for cometary ejecta leading, trailing, and following the parent comet's nucleus for 10 major meteor showers. Finally, we numerically solve for critical beta values in the case of non-geometric optics. These values determine the mass regimes within which meteoroids are ejected from the Solar System and therefore cannot contribute to meteor showers.

Purification and characterization of NADP-dependent 7 beta-hydroxysteroid dehydrogenase from Peptostreptococcus productus strain b-52.

PubMed

Masuda, N; Oda, H; Tanaka, H

1983-01-04

An NADP-dependent 7 beta-hydroxysteroid dehydrogenase was purified 11.5-fold over the activity in crude cell extracts prepared from Peptostreptococcus productus strain b-52, by using Sephadex G-200 and DEAE-cellulose column chromatography. 7 beta-Dehydrogenation was the sole transformation of bile acids catalyzed by the partially purified enzyme. The enzyme preparation (spec. act. 2.781 IU per mg protein) had an optimum pH of 9.8. Lineweaver-Burk plots showed a Michaelis constant (Km) value of 0.05 mM for 3 alpha, 7 beta-dihydroxy-5 beta-cholanoic acid whereas higher values were obtained with 3 alpha,7 beta-dihydroxy-5 beta-cholanoyl glycine (0.20 mM), and 3 alpha,7 beta-dihydroxy-5 beta-cholanoyl taurine (0.26 mM). NADP but not NAD could function as an electron acceptor, and had a Km value of 0.30 mM. A molecular weight of 64000 was determined by SDS-polyacrylamide gel electrophoresis. The addition of 0.4 mM of either bile acid to the growth medium suppressed not only cell growth, but also the enzyme yield.

Evidence for the absence of cerebral glucose-6-phosphatase activity in glycogen storage disease type I (Von Gierke's disease)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phelps, M.E.; Mazziotta, J.C.; Hawkins, R.A.

1981-01-01

Glycogen storage disease type I (GSD-I) is characterized by a functional deficit in glucose-6-phosphatase that normally hydrolyzes glucose-6-PO/sub 4/ to glucose. This enzyme is primarily found in liver, kidney, and muscle but it is also present in brain, where it appears to participate in the regulation of cerebral tissue glucose. Since most neurological symptoms in GSD-I patients involve systemic hypoglycemia, previous reports have not examined possible deficiencies in phosphatase activity in the brain. Positron computed tomography, F-18-labeled 2-fluorodeoxyglucose (FDG) and a tracer kinetic model for FDG were used to measure the cortical plasma/tissue forward and reverse transport, phosphorylation and dephosphorylationmore » rate constants, tissue/plasma concentration gradient, tissue concentration turnover rate for this competitive analog of glucose, and the cortical metabolic rates for glucose. Studies were carried out in age-matched normals (N = 13) and a single GSD-I patient. The dephosphorylation rate constant in the GSD-I patient was about one tenth the normal value indicating a low level of cerebral phosphatase activity. The other measured parameters were within normal limits except for the rate of glucose phosphorylation which reflected a cortical glucose metabolic rate one half the normal value. Since glucose transport and tissue glucose concentration was normal, the reduced cortical glucose metabolism probably results from the use of alternative substrates (..beta..-hydroxybutyrate and acetoacetate) which are consistently elevated in the plasma of GSD-I patients.« less

Effects of preventing O-glycosylation on the secretion of human chorionic gonadotropin in Chinese hamster ovary cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matzuk, M.M.; Krieger, M.; Corless, C.L.

1987-09-01

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common ..cap alpha.. subunit but differ in their hormone-specific ..beta..-subunits. The ..beta.. subunit of hCG (hCG..beta..) is unique among the ..beta.. subunits in that it contains four mucin-like O-linked oligosaccharides attached to a carboxyl-terminal extension. To study the effects of O-glycosylation on the secretion and assembly of hCG, expression vectors containing either hCG..beta.. gene alone or together with the hCG..cap alpha.. gene were transfected into a mutant Chinese hamster ovary cell line, 1d1D, which exhibits a reversible defect in O-glycosylation. The results revealmore » that hCG..beta.. can be secreted normally in the absence of its O-linked oligosaccharides. hCG..beta.. devoid of O-linked carbohydrate can also combine efficiently with hCG..cap alpha.. and be secreted as an intact dimer. The authors conclude that in Chinese hamster ovary cells, the hCG..beta.. O-linked chains play no role in the assembly and secretion of hCG. The normal and O-linked oligosaccharide-deficient forms of hCG secreted by these cells should prove useful in examining the role of O-linked chains on the biological function of hCG.« less

Particle Orbit Analysis in the Finite Beta Plasma of the Large Helical Device using Real Coordinates

NASA Astrophysics Data System (ADS)

Seki, Ryousuke; Matsumoto, Yutaka; Suzuki, Yasuhiro; Watanabe, Kiyomasa; Itagaki, Masafumi

High-energy particles in a finite beta plasma of the Large Helical Device (LHD) are numerically traced in a real coordinate system. We investigate particle orbits by changing the beta value and/or the magnetic field strength. No significant difference is found in the particle orbit classifications between the vacuum magnetic field and the finite beta plasma cases. The deviation of a banana orbit from the flux surfaces strongly depends on the beta value, although the deviation of the orbit of a passing particle is independent of the beta value. In addition, the deviation of the orbit of the passing particle, rather than that of the banana-orbit particles, depends on the magnetic field strength. We also examine the effect of re-entering particles, which repeatedly pass in and out of the last closed flux surface, in the finite beta plasma of the LHD. It is found that the number of re-entering particles in the finite beta plasma is larger than that in the vacuum magnetic field. As a result, the role of reentering particles in the finite beta plasma of the LHD is more important than that in the vacuum magnetic field, and the effect of the charge-exchange reaction on particle confinement in the finite beta plasma is large.

Regressive changes in finasteride-treated human hyperplastic prostates correlate with an upregulation of TGF-beta receptor expression.

PubMed

Sáez, C; González-Baena, A C; Japón, M A; Giráldez, J; Segura, D I; Miranda, G; Rodríguez-Vallejo, J M; González-Esteban, J; Torrubia, F

1998-10-01

Prostatic atrophy has been documented histologically as a consequence of finasteride action on human hyperplastic prostates. An increase in apoptotic rates has also been reported in androgen-deprived hyperplastic prostates. Transforming growth factor beta (TGF-beta) signaling is implicated in apoptotic cell death. TGF-betas have been detected in normal and diseased human prostate. In the normal prostate, TGF-beta acts as a predominantly negative growth regulator. TGF-beta signaling receptors TbetaRI and TbetaRII have been shown to be negatively regulated by androgens. We studied the histological changes in 9 selected finasteride-treated patients with benign prostatic hyperplasia (BPH), and analyzed the levels of expression and localization of TGF-beta receptor types TbetaRI and TbetaRII in these patients as compared to selected BPH controls. The prostatic epithelial compartment seemed to be a primary target site for finasteride action, since we observed moderate to severe glandular atrophy after 4-6 months of treatment. TGF-beta receptors were upregulated in treated cases. We assessed a twofold increase in TbetaRII mRNA levels in treated cases as compared to controls. An increase in both TbetaRI and TbetaRII at the protein level by immunostaining was observed, which also provided a helpful means for detecting glands undergoing regression. We conclude that finasteride may modulate the TGF-beta signaling system to promote changes leading to apoptosis of epithelial cells and prostatic glandular atrophy.

TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways.

PubMed

Tacheau, Charlotte; Fontaine, Juliette; Loy, Jennifer; Mauviel, Alain; Verrecchia, Franck

2008-12-01

One of the shared physiological roles between TGF-beta and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-beta1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-beta1 plays a key role in the control of NMuMG cells proliferation by TGF-beta1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-beta1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-beta1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-beta1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-beta1-induced Cx43 gene expression.

Bmi-1 extends the life span of normal human oral keratinocytes by inhibiting the TGF-{beta} signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Reuben H., E-mail: rkim@dentistry.ucla.edu; UCLA Dental Research Institute, Los Angeles, CA 90095; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095

2010-10-01

We previously demonstrated that Bmi-1 extended the in vitro life span of normal human oral keratinocytes (NHOK). We now report that the prolonged life span of NHOK by Bmi-1 is, in part, due to inhibition of the TGF-{beta} signaling pathway. Serial subculture of NHOK resulted in replicative senescence and terminal differentiation and activation of TGF-{beta} signaling pathway. This was accompanied with enhanced intracellular and secreted TGF-{beta}1 levels, phosphorylation of Smad2/3, and increased expression of p15{sup INK4B} and p57{sup KIP2}. An ectopic expression of Bmi-1 in NHOK (HOK/Bmi-1) decreased the level of intracellular and secreted TGF-{beta}1 induced dephosphorylation of Smad2/3, andmore » diminished the level of p15{sup INK4B} and p57{sup KIP2}. Moreover, Bmi-1 expression led to the inhibition of TGF-{beta}-responsive promoter activity in a dose-specific manner. Knockdown of Bmi-1 in rapidly proliferating HOK/Bmi-1 and cancer cells increased the level of phosphorylated Smad2/3, p15{sup INK4B}, and p57{sup KIP2}. In addition, an exposure of senescent NHOK to TGF-{beta} receptor I kinase inhibitor or anti-TGF-{beta} antibody resulted in enhanced replicative potential of cells. Taken together, these data suggest that Bmi-1 suppresses senescence of cells by inhibiting the TGF-{beta} signaling pathway in NHOK.« less

Elevated plasma TGF-beta1 in renal diseases: cause or consequence?

PubMed

Junker, U; Haufe, C C; Nuske, K; Rebstock, K; Steiner, T; Wunderlich, H; Junker, K; Reinhold, D

2000-07-01

We previously reported elevated levels of TGF-beta1 in patients with renal carcinoma. Certain aspects led us to ask whether they might be caused by chronic damage to the kidney(s). Here we report on an extended set of patients with various renal diseases, lung cancer, humoral immunodeficiency and controls. For latent TGF-beta1 in plasma, we find that the control, immunodeficiency, lung cancer and kidney transplant groups do not differ significantly (means, 7.0-8.8 ng/ml). Also, acute short-term renal stress (extracorporal lithotrypsy) does not lead to an increase of TGF-beta1. However, the pyelonephritis patients present with levels of 19.0 ng/ml, chronic extracorporal dialysis patients with 15.5 ng/ml, and renal cell carcinoma patients with 22.8 ng/ml. For active TGF-beta1 these findings are exactly recovered. For serum levels, only the renal carcinoma group presents with significantly elevated levels of TGF-beta1. Kidney transplantation seems to normalize TGF-beta1 levels, while in the kidney cancer patients surgery has an effect only in part of the group. We conclude that elevated plasma TGF-beta1 levels are common in at least two chronic renal disease conditions, and that it normalizes with restoration of renal function. It is tempting to speculate that chronic elevation of TGF-beta1 in these patients may be critically involved in these conditions predisposing to renal cancer. Copyright 2000 Academic Press.

Role of 11beta-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure.

PubMed

Yeyati, N L; Altuna, M E; Damasco, M C; Mac Laughlin, M A

2010-01-01

Aldosterone concentrations vary in advanced chronic renal failure (CRF). The isozyme 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2), which confers aldosterone specificity for mineralocorticoid receptors in distal tubules and collecting ducts, has been reported to be decreased or normal in patients with renal diseases. Our objective was to determine the role of aldosterone and 11beta-HSD2 renal microsome activity, normalized for glomerular filtration rate (GFR), in maintaining K+ homeostasis in 5/6 nephrectomized rats. Male Wistar rats weighing 180-220 g at the beginning of the study were used. Rats with experimental CRF obtained by 5/6 nephrectomy (N = 9) and sham rats (N = 10) were maintained for 4 months. Systolic blood pressure and plasma creatinine (Pcr) concentration were measured at the end of the experiment. Sodium and potassium excretion and GFR were evaluated before and after spironolactone administration (10 mg.kg-1.day-1 for 7 days) and 11beta-HSD2 activity on renal microsomes was determined. Systolic blood pressure (means +/- SEM; Sham = 105 +/- 8 and CRF = 149 +/- 10 mmHg) and Pcr (Sham = 0.42 +/- 0.03 and CRF = 2.53 +/- 0.26 mg/dL) were higher (P < 0.05) while GFR (Sham = 1.46 +/- 0.26 and CRF = 0.61 +/- 0.06 mL/min) was lower (P < 0.05) in CRF, and plasma aldosterone (Pald) was the same in the two groups. Urinary sodium and potassium excretion was similar in the two groups under basal conditions but, after spironolactone treatment, only potassium excretion was decreased in CRF rats (sham = 0.95 +/- 0.090 (before) vs 0.89 +/- 0.09 microEq/min (after) and CRF = 1.05 +/- 0.05 (before) vs 0.37 +/- 0.07 microEq/min (after); P < 0.05). 11beta-HSD2 activity on renal microsomes was lower in CRF rats (sham = 0.807 +/- 0.09 and CRF = 0.217 +/- 0.07 nmol.min-1.mg protein-1; P < 0.05), although when normalized for mL GFR it was similar in both groups. We conclude that K+ homeostasis is maintained during CRF development despite normal Pald levels. This adaptation may be mediated by renal 11beta-HSD2 activity, which, when normalized for GFR, became similar to that of control rats, suggesting that mineralocorticoid receptors maintain their aldosterone selectivity.

beta. -adrenergic relaxation of smooth muscle: differences between cells and tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheid, C.R.

1987-09-01

The present studies were carried out in an attempt to resolve the controversy about the Na/sup +/ dependence of ..beta..-adrenergic relaxation in smooth muscle. Previous studies on isolated smooth muscle cells from the toad stomach had suggested that at least some of the actions of ..beta..-adrenergic agents, including a stimulatory effect on /sup 45/Ca efflux, were dependent on the presence of a normal transmembrane Na/sup +/ gradient. Studies by other investigators using tissues derived from mammalian sources had suggested that the relaxing effect of ..beta..-adrenergic agents was Na/sup +/ independent. Uncertainty remained as to whether these discrepancies reflected differences betweenmore » cells and tissues or differences between species. Thus, in the present studies, the authors utilized both tissues and cells from the same source, the stomach muscle of the toad Bufo marinus, and assessed the Na/sup +/ dependence of ..beta..-adrenergic relaxation. They found that elimination of a normal Na/sup +/ gradient abolished ..beta..-adrenergic relaxation of isolated cells. In tissues, however, similar manipulations had no effect on relaxation. The reasons for this discrepancy are unclear but do not appear to be attributable to changes in smooth muscle function following enzymatic dispersion. Thus the controversy concerning the mechanisms of ..beta..-adrenergic relaxation may reflect inherent differences between tissues and cells.« less

Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice.

PubMed

Ezquer, Fernando E; Ezquer, Marcelo E; Parrau, Daniela B; Carpio, Daniel; Yañez, Alejandro J; Conget, Paulette A

2008-06-01

Multipotent mesenchymal stromal cells (MSCs), often labeled mesenchymal stem cells, contribute to tissue regeneration in injured bone and cartilage, as well as in the infarcted heart, brain, and kidney. We hypothesize that MSCs might also contribute to pancreas and kidney regeneration in diabetic individuals. Therefore, in streptozotocin (STZ)-induced type 1 diabetes C57BL/6 mice, we tested whether a single intravenous dose of MSCs led to recovery of pancreatic and renal function and structure. When hyperglycemia, glycosuria, massive beta-pancreatic islets destruction, and mild albuminuria were evident (but still without renal histopathologic changes), mice were randomly separated in 2 groups: 1 received 0.5 x 10(6) MSCs that have been ex vivo expanded (and characterized according to their mesenchymal differentiation potential), and the other group received the vehicle. Within a week, only MSC-treated diabetic mice exhibited significant reduction in their blood glucose levels, reaching nearly euglycemic values a month later. Reversion of hyperglycemia and glycosuria remained for 2 months at least. An increase in morphologically normal beta-pancreatic islets was observed only in MSC-treated diabetic mice. Furthermore, in those animals albuminuria was reduced and glomeruli were histologically normal. On the other side, untreated diabetic mice presented glomerular hyalinosis and mesangial expansion. Thus, MSC administration resulted in beta-pancreatic islets regeneration and prevented renal damage in diabetic animals. Our preclinical results suggest bone marrow-derived MSC transplantation as a cell therapy strategy to treat type 1 diabetes and prevent diabetic nephropathy, its main complication.

Synergy between TGF-beta 3 and NT-3 to promote the survival of spiral ganglia neurones in vitro.

PubMed

Marzella, P L; Clark, G M; Shepherd, R K; Bartlett, P F; Kilpatrick, T J

1998-01-09

Transforming growth factor-betas (TGF-betas) have been implicated in normal inner ear development and in promoting neuronal survival. Early rat post-natal spiral ganglion cells (SGC) in dissociated cell culture were used as a model of auditory innervation to test the trophic factors TGF-beta3 and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings from this study suggest that TGF-beta3 supports neuronal survival in a concentration-dependent manner. Moreover TGF-beta3 and NT-3-potentiated spiral ganglion neuronal survival in a synergistic fashion.

Critical analysis of the discrepancy between V(beta) and V(ss) for drugs exhibiting different two-compartment disposition profiles.

PubMed

Sobol, Eyal; Bialer, Meir

2005-03-01

It is well known that in the two-compartment open body model the values of apparent volume of distribution (V(beta)) and volume of distribution at steady state (V(ss)) are never identical. There are at least two conditions when V(beta) significantly overestimates V(ss). The first is when most of a drug is eliminated relatively rapidly but a small fraction of the dose persists and gives rise to an extremely long half-life. The second is when a drug is rapidly cleared from the central compartment with a short half-life. The primary purpose of the current paper was to investigate how different two-compartment disposition profiles affect the magnitude of difference between V(beta) and V(ss). Novel equations have been developed that relate the V(beta)/V(ss) ratio to f1 (fraction of drug elimination associated with the distributive phase) and to beta/alpha (ratio of the exponential coefficients). This paper demonstrates mathematically that an increasing value of f1 is associated with a greater divergence between V(beta) and V(ss). A similar relationship was also found for the divergence between the terminal half-life (t(1/2beta)) and the mean residence time (MRT). An increase in the beta/alpha ratio results in a substantial decrease of this discrepancy and provides a maximal possible value, or an upper limit to the V(beta)/V(ss) ratio. The newly derived equations along with their graphical presentation may serve as an excellent predictive tool for checking the accuracy of the experimentally obtained values of V(beta) and V(ss). Copyright 2004 John Wiley & Sons, Ltd.

Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion.

PubMed

Horai, R; Asano, M; Sudo, K; Kanuka, H; Suzuki, M; Nishihara, M; Takahashi, M; Iwakura, Y

1998-05-04

Interleukin (IL)-1 is a major mediator of inflammation and exerts pleiotropic effects on the neuro-immuno-endocrine system. To elucidate pathophysiological roles of IL-1, we have first produced IL-1alpha/beta doubly deficient (KO) mice together with mice deficient in either the IL-1alpha, IL-1beta, or IL-1 receptor antagonist (IL-1ra) genes. These mice were born healthy, and their growth was normal except for IL-1ra KO mice, which showed growth retardation after weaning. Fever development upon injection with turpentine was suppressed in IL-1beta as well as IL-1alpha/beta KO mice, but not in IL-1alpha KO mice, whereas IL-1ra KO mice showed an elevated response. At this time, expression of IL-1beta mRNA in the diencephalon decreased 1.5-fold in IL-1alpha KO mice, whereas expression of IL-1alpha mRNA decreased >30-fold in IL-1beta KO mice, suggesting mutual induction between IL-1alpha and IL-1beta. This mutual induction was also suggested in peritoneal macrophages stimulated with lipopolysaccharide in vitro. In IL-1beta KO mice treated with turpentine, the induction of cyclooxygenase-2 (EC 1.14.99.1) in the diencephalon was suppressed, whereas it was enhanced in IL-1ra KO mice. We also found that glucocorticoid induction 8 h after turpentine treatment was suppressed in IL-1beta but not IL-1alpha KO mice. These observations suggest that IL-1beta but not IL-1alpha is crucial in febrile and neuro-immuno-endocrine responses, and that this is because IL-1alpha expression in the brain is dependent on IL-1beta. The importance of IL-1ra both in normal physiology and under stress is also suggested.

hCG Test (Pregnancy Test)

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... Us Also Known As Pregnancy Test Qualitative hCG Quantitative hCG Beta hCG Total hCG Total beta hCG ...

Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

USDA-ARS?s Scientific Manuscript database

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

Dynamic radioactive particle source

DOEpatents

Moore, Murray E; Gauss, Adam Benjamin; Justus, Alan Lawrence

2012-06-26

A method and apparatus for providing a timed, synchronized dynamic alpha or beta particle source for testing the response of continuous air monitors (CAMs) for airborne alpha or beta emitters is provided. The method includes providing a radioactive source; placing the radioactive source inside the detection volume of a CAM; and introducing an alpha or beta-emitting isotope while the CAM is in a normal functioning mode.

Immune defects in families and patients with xeroderma pigmentosum and trichothiodystrophy.

PubMed Central

Mariani, E; Facchini, A; Honorati, M C; Lalli, E; Berardesca, E; Ghetti, P; Marinoni, S; Nuzzo, F; Astaldi Ricotti, G C; Stefanini, M

1992-01-01

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity, a high incidence of cancer in sun-exposed portions of the skin and a reduced capacity to repair the u.v.-induced DNA damage. One of the XP mutations (XP-D) has also been identified in patients affected by trichothiodystrophy (TTD), a rare autosomal recessive disease characterized by brittle hair, mental and physical retardation, peculiar face and ichthyosis. However, in these patients there is no evidence of increased skin tumour incidence. Since an impairment of cell-mediated immunity has been proposed as a co-factor in the cancer proneness of XP patients, we investigated the involvement of immune defect(s) in five XP patients, five TTD patients, their parents, and 24 TTD relatives. We evaluated the phenotype of circulating lymphocytes, natural killer (NK) cell lytic activity, target cell binding of NK cells at single cell level and the effect of interferons (IFN) alpha and beta on NK cell activity. The relative proportion of CD3+ and CD4+ circulating lymphocytes was reduced in XP but not in TTD patients. NK cell lytic activity was decreased in XP patients and their mothers, but their fathers showed normal lytic activity. NK activity varied among TTD families: four out of five patients and their relatives presented low NK cell activity, and one family was normal. In TTD family members, NK activity increased after incubation with IFN-alpha or IFN-beta, but never reached normal values. In contrast, in XP patients and their mothers, the defect was almost completely corrected after in vitro incubation with IFN-alpha or IFN-beta. Our study indicates impaired NK lytic activity in the majority of TTD and XP patients and that this defect is present also in members of their families. In addition, XP patients present a low number of circulating T cells. These multiple abnormalities, together with DNA repair defects, could be related to the increased cancer risk in XP patients. PMID:1535035

Loss of intra-islet heparan sulfate is a highly sensitive marker of type 1 diabetes progression in humans.

PubMed

Simeonovic, Charmaine J; Popp, Sarah K; Starrs, Lora M; Brown, Debra J; Ziolkowski, Andrew F; Ludwig, Barbara; Bornstein, Stefan R; Wilson, J Dennis; Pugliese, Alberto; Kay, Thomas W H; Thomas, Helen E; Loudovaris, Thomas; Choong, Fui Jiun; Freeman, Craig; Parish, Christopher R

2018-01-01

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells in pancreatic islets are progressively destroyed. Clinical trials of immunotherapies in recently diagnosed T1D patients have only transiently and partially impacted the disease course, suggesting that other approaches are required. Our previous studies have demonstrated that heparan sulfate (HS), a glycosaminoglycan conventionally expressed in extracellular matrix, is present at high levels inside normal mouse beta cells. Intracellular HS was shown to be critical for beta cell survival and protection from oxidative damage. T1D development in Non-Obese Diabetic (NOD) mice correlated with loss of islet HS and was prevented by inhibiting HS degradation by the endoglycosidase, heparanase. In this study we investigated the distribution of HS and heparan sulfate proteoglycan (HSPG) core proteins in normal human islets, a role for HS in human beta cell viability and the clinical relevance of intra-islet HS and HSPG levels, compared to insulin, in human T1D. In normal human islets, HS (identified by 10E4 mAb) co-localized with insulin but not glucagon and correlated with the HSPG core proteins for collagen type XVIII (Col18) and syndecan-1 (Sdc1). Insulin-positive islets of T1D pancreases showed significant loss of HS, Col18 and Sdc1 and heparanase was strongly expressed by islet-infiltrating leukocytes. Human beta cells cultured with HS mimetics showed significantly improved survival and protection against hydrogen peroxide-induced death, suggesting that loss of HS could contribute to beta cell death in T1D. We conclude that HS depletion in beta cells, possibly due to heparanase produced by insulitis leukocytes, may function as an important mechanism in the pathogenesis of human T1D. Our findings raise the possibility that intervention therapy with dual activity HS replacers/heparanase inhibitors could help to protect the residual beta cell mass in patients recently diagnosed with T1D.

Numerical Analysis of the Effects of Normalized Plasma Pressure on RMP ELM Suppression in DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orlov, D. M.; Moyer, R.A.; Evans, T. E.

2010-01-01

The effect of normalized plasma pressure as characterized by normalized pressure parameter (beta(N)) on the suppression of edge localized modes (ELMs) using resonant magnetic perturbations (RMPs) is studied in low-collisionality (nu* <= 0.2) H-mode plasmas with low-triangularity ( = 0.25) and ITER similar shapes ( = 0.51). Experimental results have suggested that ELM suppression by RMPs requires a minimum threshold in plasma pressure as characterized by beta(N). The variations in the vacuum field topology with beta(N) due to safety factor profile and island overlap changes caused by variation of the Shafranov shift and pedestal bootstrap current are examined numerically withmore » the field line integration code TRIP3D. The results show very small differences in the vacuum field structure in terms of the Chirikov (magnetic island overlap) parameter, Poincare sections and field line loss fractions. These differences do not appear to explain the observed threshold in beta(N) for ELM suppression. Linear peeling-ballooning stability analysis with the ELITE code suggests that the ELMs which persist during the RMPs when beta(N) is below the observed threshold are not type I ELMs, because the pedestal conditions are deep within the stable regime for peeling-ballooning modes. These ELMs have similarities to type III ELMs or low density ELMs.« less

Gray Matter Network Disruptions and Regional Amyloid Beta in Cognitively Normal Adults.

PubMed

Ten Kate, Mara; Visser, Pieter Jelle; Bakardjian, Hovagim; Barkhof, Frederik; Sikkes, Sietske A M; van der Flier, Wiesje M; Scheltens, Philip; Hampel, Harald; Habert, Marie-Odile; Dubois, Bruno; Tijms, Betty M

2018-01-01

The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects ( n = 318, mean age 76.1 ± 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [ 18 F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering ( β = -0.12, p < 0.05), and small world values ( β = -0.16, p < 0.01). Associations were most prominent in orbito- and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.

Electroencephalographic coherences discriminate between children with different pedagogical evaluation.

PubMed

Marosi, E; Harmony, T; Becker, J; Reyes, A; Bernal, J; Fernández, T; Rodríguez, M; Silva, J; Guerrero, V

1995-02-01

The relationship of reading-writing ability and EEG coherences was studied in 84 subjects from two age groups 7.0-8.9 and 9-11.2 years old. All children were divided into three groups according to their performance on a pedagogical test: ped1, normal children; ped2, children with mild problems; ped3, children with reading-writing disability. The following results were obtained: in general, children showed higher coherences in groups with poor performance in the delta, theta and beta bands. In the alpha band, higher coherence values were related to better performance. The exceptions to this general pattern were rare. Group ped2 had higher coherences in delta, theta and alpha bands than ped1 and ped3, in left temporal leads. In older children the same tendency was observed, but group differences in the theta, alpha and beta bands were few. In this age range, the significant group differences were almost all interhemispheric coherences. The discriminant analysis that classified subjects by their coherence values gave very good results, fact that demonstrates, that EEG coherence is a highly sensitive measurement indicating not only the existence of a reading-writing problem, but also the degree of its severity.

Normal T lymphocytes can express two different T cell receptor beta chains: implications for the mechanism of allelic exclusion

PubMed Central

1995-01-01

We have examined the extent of allelic exclusion at the T cell receptor (TCR) beta locus using monoclonal antibodies specific for V beta products. A small proportion (approximately 1%) of human peripheral blood T cells express two V beta as determined by flow cytometric analysis, isolation of representative clones, and sequencing of the corresponding V beta chains. Dual beta T cells are present in both the CD45R0+ and CD45R0- subset. These results indicate that dual beta expression is compatible with both central and peripheral selection. They also suggest that the substantial degree of TCR beta allelic exclusion is dependent only on asynchronous rearrangements at the beta locus, whereas the role of the pre-TCR is limited to signaling the presence of at least one functional beta protein. PMID:7699339

Vitamin E supplement improves erythrocyte membrane fluidity of thalassemia: an ESR spin labeling study.

PubMed

Sutipornpalangkul, Werasak; Morales, Noppawan Phumala; Unchern, Supeenun; Sanvarinda, Yupin; Chantharaksri, Udom; Fucharoen, Suthat

2012-01-01

Beta-thalassemia/Hemoglobin E (beta-thal/Hb E) is prevalent in Thailand. The imbalance of globin chains in red blood cells is the primary cause of this anemic disease. The excess alpha-globin in beta-thal/Hb E causes typical damage(s) to membrane of erythroblasts and erythrocytes. By using three paramagnetic labeled compounds (5-, 12-, and 16-spin labeled stearic acids, SLS), the changes of the molecular motion in the lipid bilayer of thalassemic RBCs that have structural modification can be detected. to investigate erythrocyte membrane fluidity and the effect of vitamin E treatment in beta-thalassemia/Hemoglobin E patients by using spin labeling techniques. The erythrocyte membrane fluidity was investigated in nine splenectomized and five non-splenectomized beta-thalassemia/hemoglobin E (beta-thal/Hb E) patients using EPR spin labeling techniques. To determine the effect of vitamin E on erythrocyte membrane fluidity, only the splenectomized patients were enrolled. Patients were divided into two groups. The first group received 350 mg vitamin E daily for a period of 1 month (n = 5) and the second group received placebo for an equal period (n = 4). Three paramagnetic fatty acid, 5-, 12-, and 16-doxyl stearic acids, (5-, 12- and 16-DS) were used to label phospholipids layer near both the surface (5-DS) and the deeper hydrophobic region of membrane (12-and 16-DS). Lipid peroxidation (TBARs) was measured using a colorimetric method. Vitamin E was measured with high performance liquid chromatography (HPLC). Significantly higher values of erythrocyte membrane fluidity were revealed with 12-, 16-DS in splenectomized patients, as compared with non-splenectomized patients and normal subjects. In 3-thal/Hb E patients, fluidity values, both outer hyperfine splitting (2T(//)) and order parameter (S) of 12-DS showed inverse correlation with serum TBARs. There was no significant difference between the fluidity values measured with 5-DS. After vitamin E supplementation, the erythrocyte membrane fluidity was decreased in almost all patients. In contrast to the vitamin E supplementation group, increased erythrocyte membrane fluidity was demonstrated in the placebo group. Vitamin E supplementation also had effect on other clinical parameters such as increased plasma vitamin E, decreased serum TBARs and no change in hemoglobin. The present results suggested the abnormal motion of lipid in the deeper phospholipids region of membrane. In addition, vitamin E supplementation may have a role in the prevention of erythrocyte membrane damage of these patients.

The costo-uterine muscle of the rat contains a homogeneous population of beta-adrenoceptors.

PubMed Central

Hartley, M. L.; Pennefather, J. N.

1985-01-01

The effects of two selective beta-adrenoceptor antagonists on the inhibitory responses to some sympathomimetic amines of electrically-stimulated preparations of costo-uterine muscle, taken from virgin rats, have been examined quantitatively. pA2 values for the antagonist, atenolol (beta 1-selective) and ICI 118,551 (beta 2-selective) were obtained using as agonists, fenoterol (beta 2-selective agonist) and noradrenaline (alpha- and beta-adrenoceptor agonist, beta 1-selective); and in addition, with ICI 118,551 only, isoprenaline (beta-agonist, non-selective) and adrenaline (alpha- and beta-adrenoceptor agonist, beta 2-selective). Catecholamine uptake mechanisms and alpha-adrenoceptors were not blocked in any of these experiments. Atenolol competitively antagonized the effects of fenoterol and noradrenaline to a similar extent, the pA2 values being 5.4 and 5.7, respectively. ICI 118,551 competitively antagonized the effects of fenoterol, isoprenaline, adrenaline and noradrenaline to a similar extent; pA2 values ranged from 8.7 with noradrenaline to 9.1 with isoprenaline. These results extend our previous observations which indicated that the adrenoceptors mediating inhibition of electrically-evoked contractions of costo-uterine muscle of the virgin rat are homogeneous and of the beta 2-subtype. The potency of the beta 1-selective agonist RO 363 in producing inhibition of electrically-evoked contractions of this tissue was also examined. RO 363 was 200 times less potent than isoprenaline but was a full agonist. This indicates that there is efficient coupling between beta 2-adrenoceptor activation and tissue response in this non-innervated preparation. PMID:2858239

Characterization of a beta-glucanase produced by Rhizopus microsporus var. microsporus, and its potential for application in the brewing industry.

PubMed

Celestino, Klecius R Silveira; Cunha, Ricardo B; Felix, Carlos R

2006-12-05

In the barley malting process, partial hydrolysis of beta-glucans begins with seed germination. However, the endogenous 1,3-1,4-beta-glucanases are heat inactivated, and the remaining high molecular weight beta-glucans may cause severe problems such as increased brewer mash viscosity and turbidity. Increased viscosity impairs pumping and filtration, resulting in lower efficiency, reduced yields of extracts, and lower filtration rates, as well as the appearance of gelatinous precipitates in the finished beer. Therefore, the use of exogenous beta-glucanases to reduce the beta-glucans already present in the malt barley is highly desirable. The zygomycete microfungus Rhizopus microsporus var. microsporus secreted substantial amounts of beta-glucanase in liquid culture medium containing 0.5% chitin. An active protein was isolated by gel filtration and ion exchange chromatographies of the beta-glucanase activity-containing culture supernatant. This isolated protein hydrolyzed 1,3-1,4-beta-glucan (barley beta-glucan), but showed only residual activity against 1,3-beta-glucan (laminarin), or no activity at all against 1,4-beta-glucan (cellulose), indicating that the R. microsporus var. microsporus enzyme is a member of the EC 3.2.1.73 category. The purified protein had a molecular mass of 33.7 kDa, as determined by mass spectrometry. The optimal pH and temperature for hydrolysis of 1,3-1,4-beta-glucan were in the ranges of 4-5, and 50-60 degrees C, respectively. The Km and Vmax values for hydrolysis of beta-glucan at pH 5.0 and 50 degrees C were 22.39 mg.mL-1 and 16.46 mg.min-1, respectively. The purified enzyme was highly sensitive to Cu+2, but showed less or no sensitivity to other divalent ions, and was able to reduce both the viscosity and the filtration time of a sample of brewer mash. In comparison to the values determined for the mash treated with two commercial glucanases, the relative viscosity value for the mash treated with the 1,3-1,4-beta-glucanase produced by R. microsporus var. microsporus. was determined to be consistently lower. The zygomycete microfungus R. microsporus var. microsporus produced a 1,3-1,4-beta-D-glucan 4-glucanhydrolase (EC 3.2.1.73) which is able to hydrolyze beta-D-glucan that contains both the 1,3- and 1,4-bonds (barley beta-glucans). Its molecular mass was 33.7 kDa. Maximum activity was detected at pH values in the range of 4-5, and temperatures in the range of 50-60 degrees C. The enzyme was able to reduce both the viscosity of the brewer mash and the filtration time, indicating its potential value for the brewing industry.

Atypical neural synchronization to speech envelope modulations in dyslexia.

PubMed

De Vos, Astrid; Vanvooren, Sophie; Vanderauwera, Jolijn; Ghesquière, Pol; Wouters, Jan

2017-01-01

A fundamental deficit in the synchronization of neural oscillations to temporal information in speech could underlie phonological processing problems in dyslexia. In this study, the hypothesis of a neural synchronization impairment is investigated more specifically as a function of different neural oscillatory bands and temporal information rates in speech. Auditory steady-state responses to 4, 10, 20 and 40Hz modulations were recorded in normal reading and dyslexic adolescents to measure neural synchronization of theta, alpha, beta and low-gamma oscillations to syllabic and phonemic rate information. In comparison to normal readers, dyslexic readers showed reduced non-synchronized theta activity, reduced synchronized alpha activity and enhanced synchronized beta activity. Positive correlations between alpha synchronization and phonological skills were found in normal readers, but were absent in dyslexic readers. In contrast, dyslexic readers exhibited positive correlations between beta synchronization and phonological skills. Together, these results suggest that auditory neural synchronization of alpha and beta oscillations is atypical in dyslexia, indicating deviant neural processing of both syllabic and phonemic rate information. Impaired synchronization of alpha oscillations in particular demonstrated to be the most prominent neural anomaly possibly hampering speech and phonological processing in dyslexic readers. Copyright © 2016 Elsevier Inc. All rights reserved.

Direct-normal solar irradiance measurements and turbidity coefficient evaluation in central Spain.

NASA Astrophysics Data System (ADS)

Bllbao, Julia; Román, Roberto; Miguel, Argimiro

2013-04-01

In order to study the characteristics of solar direct radiation and the atmospheric turbidity in Valladolid, Spain, global, diffuse and direct irradiance data were recorded from May 2010 to December 2011, with a frequency of 10 minute. Measurements used were taken by the Energy and Atmosphere Group (http://www3.uva.es/renova), University of Valladolid, Spain at the Solar Radiometric Station (41,81°N 4.93°W, 840m a.s.l.) located on the Atmosphere Researcher Centre, Villalba de los Alcores, Valladolid, Spain. Sensors were installed in a Sun tracker (Solys 2, Kipp & Zonen) that blocks direct solar radiation using a shadow ball. The system consists of two pyranometers CMP-21 and one pyrheliometer CHP-1 (Kipp & Zonen), respectively. Based on these measurements, the characteristics of direct solar irradiance data were evaluated in order to know the main statistical parameters of the distribution. Angström turbidity coefficient values, beta, were estimated from direct solar irradiance and clear sky conditions. The beta coefficient values were obtained from MODIS satellite instrument, and the aerosol optical depth values, AOD(550nm), were evaluated. The turbidity coefficient beta shows seasonal variation, with higher values in summer (< 0.15) and lower in winter (< 0.05). It could be due to high temperatures in summer and less rainy days which would induce more atmospheric turbidity, increasing vertical convection and particles enhancement. The scattered graph of aerosol optical depth from satellite and the obtained from Angström expression has been plotted. The slope presents a value around the unity, 0.96, and the correlation coefficient shows a value of 0.6 . It was observed that turbidity coefficients increased in April 2011, and in order to now the origin the change, air masses trajectories, deduced from HYSPLIT model (http://ready.arl.noaa.gov/HYSPLIT.php) were studied. From the results it has been obtained that a situation of low pressures in the Atlantic Portuguese coast and high pressure in the North of Spain induced the movement of dust from Sahara desert into the Iberian Peninsula.

The effect of a low carotenoid diet on malondialdehyde-thiobarbituric acid (MDA-TBA) concentrations in women: a placebo-controlled double-blind study.

PubMed

Dixon, Z R; Shie, F S; Warden, B A; Burri, B J; Neidlinger, T R

1998-02-01

The purpose of the study was to evaluate the effect of a low carotenoid diet (83 micrograms Beta-carotene) on malondialdehyde-thiobarbituric acid (MDA-TBA) concentrations of nine pre-menopausal women. Subjects lived on the metabolic research unit of the Western Human Nutrition Research Center (WHNRC), where diet, exercise and other activities were controlled. Five subjects (Group C, control group) consumed a low carotenoid diet and received an additional 0.5 mg/day of Beta-carotene while four subjects (Group P, placebo group) received only the low carotenoid diet during days 1 to 60 (period 1). All subjects received 0.5 mg/day of Beta-carotene during days 60 to 100 (period 2), plus three capsules/day mixed carotenoid supplement (Neo-Life Company) during study days 100 to 120. Changes in MDA-TBA concentrations were analyzed during the study periods and between the groups. At the start of the study (day 1), no significant difference in the MDA-TBA concentration was observed between the control (Group C) and the placebo (Group P) subjects. During period 1 (days 2 to 60), when Group P subjects consumed the low carotenoid diet without supplementation, the MDA-TBA values for Group P rose markedly and were significantly (p < 0.05) higher than the MDA-TBA values for Group C subjects who were receiving carotenoid supplementation. During period 2 (days 60 to 100) when both groups received carotenoid supplementation, the MDA-TBA values of Group P subjects were significantly (p < 0.05) reduced to the point where they were similar to the MDA-TBA values for Group C subjects. These findings provide evidence to support the beneficial effects of carotenoids in preventing lipid peroxidation in the cells. Further studies are needed to identify the exact mechanism by which carotenoids prevent lipid peroxidation and the amount needed for normal activity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, G.F.; Marks, B.H.

This study examines the beta adrenergic receptors of the rabbit detrusor smooth muscle, employing (/sup 125/I)iodocyanopindolol (ICYP) as a ligand for the binding of beta adrenergic receptors. Saturation binding experiments on the isolated membrane fraction yielded a KD for ICYP of 14.7 pM and a maximum binding of 147.6 fmol/mg of protein. Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM. When these displacement experimental results weremore » compared to KD values from other reported binding studies with ICYP for beta adrenoreceptors, both the order of potency and the KD values indicated primarily beta-2 adrenergic receptor subtypes. Computer program Scatfit analysis of the displacement curves indicated a single slope and affinity constant for all five beta adrenergic agents. Hofstee plots for zinterol, ICI 118,551 and metoprolol, however, were not linear and indicated that minor populations of beta-1 adrenoreceptors were also present as both high and low affinity binding sites could be defined. It is concluded that the primary receptor population is beta-2 and that this tissue is heterogenous with a small population of beta-1 adrenoreceptors representing approximately 13 to 23% of the total beta adrenoreceptor population.« less

Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus.

PubMed

Bellinger, F P; Madamba, S; Siggins, G R

1993-11-19

Cytokines such as interleukin-1 beta (IL-1 beta) are released in the nervous system following inflammation or infection. Recently, IL-1 beta was shown to enhance synaptic inhibitory mechanisms. We therefore investigated the effect of IL-1 beta superfusion on long-term potentiation (LTP), the cellular model of memory and learning, evoked in the CA1 region by tetanic stimulation of the stratum radiatum in the rat hippocampal slice. IL-1 beta (150 pM-1.5 nM) superfused 10 min before tetanic stimulation significantly reduced LTP of the slope of the population excitatory postsynaptic potential (pEPSP) and the population spike (PS) amplitude in CA1 in a concentration-dependent manner. IL-1 beta (1.5 nM) applied for 10 min 1 h before tetanus significantly inhibited LTP of the PS amplitude and pEPSP slope and reduced pEPSP and PS values before tetanus as well, although the PS returned to control values before tetanus. Heat-inactivated IL-1 beta had no effect on pre-tetanus pEPSP or PS values or the induction of LTP. These data demonstrate that IL-1 beta modulates synaptic potentials and reduces LTP. These findings have important implications for the role of IL-1 beta in neuronal disorders following infection, perhaps best exemplified by HIV-1-associated dementia.

Metabolic clearance and blood production rates of estradiol in hyperthyroidism.

PubMed

Ridgway, E C; Longcope, C; Maloof, F

1975-09-01

The metabolic clearance rate of 17beta-estradiol (MCR2), the plasma levels of 17beta-estradiol (E2)1, sex-steroid binding globulin (SSBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in 10 hyperthyroid subjects (7 men and 3 women). The blood production rate of 17beta-estradiol (PB2) was calculated for all subjects. Nine of the 10 hyperthyroid subjects had a decreased MCR2 which returned towards normal in 5 of the 6 subjects restudied following therapy. In all 10 subjects the levels of SSBG were increased when they were hyperthyroid and returned toward normal with therapy. It is concluded that the decrease in MCR2 is largely due to the increased binding of 17beta-estradiol to SSBG. In 7 of the 10 hyperthyroid the plasma E2 concentrations were normal whereas 3 had slightly elevated levels. In 8 of the 10 hyperthyroid the PB2 was within the normal range. Only 2 hyperthyroid subjects had slightly elevated PB2. In the 6 subjects who were restudied after therapy, there was no consistent change in PB2 which remained in the normal range in all cases. It is concluded that the MCR2 is decreased in most subjects with hyperthyroidism in association with an increase of SSBG. Despite this change in MCR2 there is no significant change in PB2. The increase in SSBG levels in hyperthyroidism appears to be a direct effect of the elevation of thyroid hormone activity and is not mediated through estrogen.

GM2-gangliosidosis variant 0 (Sandhoff-like disease) in a family of Japanese domestic cats.

PubMed

Yamato, O; Matsunaga, S; Takata, K; Uetsuka, K; Satoh, H; Shoda, T; Baba, Y; Yasoshima, A; Kato, K; Takahashi, K; Yamasaki, M; Nakayama, H; Doi, K; Maede, Y; Ogawa, H

2004-12-04

A five-month-old, female Japanese domestic shorthair cat with proportionate dwarfism developed neurological disorders, including ataxia, decreased postural responses and generalised body and head tremors, at between two and five months of age. Leucocytosis due to lymphocytosis with abnormal cytoplasmic vacuolations was observed. The concentration of G(M2)-ganglioside in its cerebrospinal fluid was markedly higher than in normal cats, and the activities of beta-hexosaminidases A and B in its leucocytes were markedly reduced. On the basis of these biochemical data, the cat was diagnosed antemortem with G(M2)-gangliosidosis variant 0 (Sandhoff-like disease). The neurological signs became more severe and the cat died at 10 months of age. Histopathologically, neurons throughout the central nervous system were distended, and an ultrastructural study revealed membranous cytoplasmic bodies in these distended neurons. The compound which accumulated in the brain was identified as G(M2)-ganglioside, confirming G(M2)-gangliosidosis. A family study revealed that there were probable heterozygous carriers in which the activities of leucocyte beta-hexosaminidases A and B were less than half the normal value. The Sandhoff-like disease observed in this family of Japanese domestic cats is the first occurrence reported in Japan.

CLINICAL APPLICATION OF RECOMBINANT ERYTHROPOIETIN IN BETA-THALASSAEMIA INTERMEDIA.

PubMed

Asadov, Ch; Alimirzoyeva, Z; Hasanova, M; Mammadova, T; Shirinova, A

2016-06-01

Research objective is to study the efficacy of recombinant erythropoietin (epoetin alfa) as alternative method of treatment beta-thalassemia intermedia. Study involved 58 patients with beta-thalassemia intermedia (23 women and 35 men). In all observed patients was defined levels of hemoglobin (Hb), red blood cells (RBC), erythrocyte indexes (MCV, MCH, MCHC), hemoglobin fractions (HbA, HbA2, HbF), serum ferritin, serum erythropoietin before and after administrated rEPO. All patients received rEPO during 6 month at the dose - 10000 IU subcutaneously. The majority of patients - 39 (67%) had a good response to rEPO (increase in hemoglobin level more than 20 g/l); 16 patients (28%) had a mean response (increase in Hb 10 - 20 g/l); in 3 (5%) patients occurred poor response to rEPO therapy (increase in Hb <10 g/l). After rEPO treatment of beta-thalassemia intermedia patients there was a statistically significant change in the number of RBC, levels of HbF and sEPO. The evaluation of interdependence between the indices of the baseline sEPO and increased Hb values in patients after rEPO treatment revealed the presence of the reverse direct relationship (r=-0.67). Based on the results, it can be concluded that the use of rEPO in complex therapy of beta-thalassemia intermedia leads to increased levels of Hb and consequently reducing the need for blood transfusions, and accordingly expected to prevent severe complications of blood transfusion (alloimmunization, hypersplenism, iron overload, contamination transmissible infections) facilitating normal growth and development, and a better quality of life.

New insights into the dual role of TGF-beta | Center for Cancer Research

Cancer.gov

The dual role of TGF-beta in cancer continues to challenge investigators in the field. TGF-beta is a well-known factor associated with tumor suppression in normal cells and yet promotes tumor progression in advanced stages of cancer. For years, the mechanisms that underpin this conundrum have not been fully understood. Ying Zhang, Ph.D., senior investigator in the Laboratory

A molecular study of a family with Greek hereditary persistence of fetal hemoglobin and beta-thalassemia.

PubMed Central

Giglioni, B; Casini, C; Mantovani, R; Merli, S; Comi, P; Ottolenghi, S; Saglio, G; Camaschella, C; Mazza, U

1984-01-01

A family was studied in which two inherited defects of the non-alpha-globin cluster segregate: Greek hereditary persistence of fetal hemoglobin (HPFH) and beta-thalassemia. Fragments of the non-alpha-globin cluster from two patients were cloned in cosmid and phage lambda vectors, and assigned to either the HPFH or beta-thalassemic chromosome on the basis of the demonstration of a polymorphic BglII site in the HPFH gamma-globin cluster. The thalassemic beta-globin gene carries a mutation at nucleotide 1 of the intervening sequence I, known to cause beta zero-thalassemia; the beta-globin gene from the HPFH chromosome is entirely normal, both in the intron-exon sequence and in 5' flanking regions required for transcription. As the compound HPFH/beta-thalassemia heterozygote synthesizes HbA, these data prove that the HPFH beta-globin gene is functional, although at a decreased rate; its lower activity is likely to be due to a distant mutation. The HPFH A gamma-globin gene shows only two mutations: a T----C substitution in the large intervening sequence (responsible for the BglII polymorphic site) and a C----T substitution 196 nucleotides 5' to the cap site; the 5' flanking sequence is normal up to -1350 nucleotides upstream from the gene. Circumstantial evidence suggests that the mutation at -196 may be responsible for the abnormally high expression of the A gamma-globin gene. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. PMID:6210198

Serum 11 beta-hydroxyandrostenedione as an indicator of the source of excess androgen production in women with polycystic ovaries.

PubMed

Polson, D W; Reed, M J; Franks, S; Scanlon, M J; James, V H

1988-05-01

Serum 11 beta-hydroxyandrostenedione levels (11-OHA) were measured in normal women and women with polycystic ovaries (PCO) to assess their value in localizing the source of excessive androgen production in women with PCO. Serum 11-OHA was undetectable (less than 1.5 nmol/L) in an adrenalectomized woman, a woman with 11-hydroxylase deficiency, and a woman receiving chronic dexamethasone therapy, confirming the specificity of the antiserum used in this study. Serum 11-OHA concentrations were similar in normal women [mean, 5.0 +/- 2.3 (+/- SD) nmol/L] and women with PCO (5.0 +/- 2.1 nmol/L); serum androstenedione concentrations were increased in women with PCO. Thus, the ratio of androstenedione to 11-OHA was significantly higher (P less than 0.001) in women with PCO (2.0 +/- 0.7) than in normal women (1.1 +/- 0.5). Serum 11-OHA levels after adrenal suppression or stimulation were similar in women with PCO who had an ovulatory response and those who failed to ovulate after clomiphene administration. Administration of dexamethasone (1 mg) and injection of ACTH (250 micrograms) were associated with marked suppression and subsequent stimulation of serum 11-OHA levels in both normal women and women with PCO, and the responses were similar in the two groups. Also, the hour to hour and diurnal variations in serum 11-OHA were similar to those of androstenedione and cortisol during a 24-h period, indicating the adrenal origin of 11-OHA. Our finding of similar serum 11-OHA levels in the presence of increased serum androstenedione levels in women with PCO supports the concept that the ovary is the major source of excess androgen production in women with PCO.

β-Arrestin2 plays a key role in the modulation of the pancreatic beta cell mass in mice.

PubMed

Ravier, Magalie A; Leduc, Michele; Richard, Joy; Linck, Nathalie; Varrault, Annie; Pirot, Nelly; Roussel, Morgane M; Bockaert, Joël; Dalle, Stéphane; Bertrand, Gyslaine

2014-03-01

Beta cell failure due to progressive secretory dysfunction and limited expansion of beta cell mass is a key feature of type 2 diabetes. Beta cell function and mass are controlled by glucose and hormones/neurotransmitters that activate G protein-coupled receptors or receptor tyrosine kinases. We have investigated the role of β-arrestin (ARRB)2, a scaffold protein known to modulate such receptor signalling, in the modulation of beta cell function and mass, with a specific interest in glucagon-like peptide-1 (GLP-1), muscarinic and insulin receptors. β-arrestin2-knockout mice and their wild-type littermates were fed a normal or a high-fat diet (HFD). Glucose tolerance, insulin sensitivity and insulin secretion were assessed in vivo. Beta cell mass was evaluated in pancreatic sections. Free cytosolic [Ca(2+)] and insulin secretion were determined using perifused islets. The insulin signalling pathway was evaluated by western blotting. Arrb2-knockout mice exhibited impaired glucose tolerance and insulin secretion in vivo, but normal insulin sensitivity compared with wild type. Surprisingly, the absence of ARRB2 did not affect glucose-stimulated insulin secretion or GLP-1- and acetylcholine-mediated amplifications from perifused islets, but it decreased the islet insulin content and beta cell mass. Additionally, there was no compensatory beta cell mass expansion through proliferation in response to the HFD. Furthermore, Arrb2 deletion altered the islet insulin signalling pathway. ARRB2 is unlikely to be involved in the regulation of insulin secretion, but it is required for beta cell mass plasticity. Additionally, we provide new insights into the mechanisms involved in insulin signalling in beta cells.

9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson's disease.

PubMed

Wernicke, Catrin; Hellmann, Julian; Zieba, Barbara; Kuter, Katarzyna; Ossowska, Krystyna; Frenzel, Monika; Dencher, Norbert A; Rommelspacher, Hans

2010-01-01

In a previous study, a primary culture of midbrain cells was exposed to 9-methyl-beta-carboline for 48 h, which caused an increase in the number of tyrosine hydroxylase-positive cells. Quantitative RT-PCR revealed increased transcription of genes participating in the maturation of dopaminergic neurons. These in vitro findings prompted us to investigate the restorative actions of 9-methyl-beta-carboline in vivo. The compound was delivered for 14 days into the left cerebral ventricle of rats pretreated with the neurotoxin 1-methyl-4-phenyl-pyridinium ion (MPP+) for 28 days applying a dose which lowered dopamine by approximately 50%. Interestingly, 9-methyl-beta-carboline reversed the dopamine-lowering effect of the neurotoxin in the left striatum. Stereological counts of tyrosine hydroxylase-immunoreactive cells in the substantia nigra revealed that the neurotoxin caused a decrease in the number of those cells. However, when treated subsequently with 9-methyl-beta-carboline, the number reached normal values. In search of an explanation for the restorative activity, we analyzed the complexes that compose the respiratory chain in striatal mitochondria by 2-dimension gel electrophoresis followed by MALDI-TOF peptide mass fingerprinting.We found no changes in the overall composition of the complexes. However, the activity of complex I was increased by approximately 80% in mitochondria from rats treated with MPP+ and 9-methyl-beta-carboline compared to MPP+ and saline and to sham-operated rats, as determined by measurements of nicotinamide adenine dinucleotide dehydrogenase activity. Microarray technology and single RT-PCR revealed the induction of neurotrophins: brain-derived neurotrophic factor, conserved dopamine neurotrophic factor, cerebellin 1 precursor protein, and ciliary neurotrophic factor. Selected western blots yielded consistent results. The findings demonstrate restorative effects of 9-methyl-beta-carboline in an animal model of Parkinson's disease that improve the effectiveness of the respiratory chain and promote the transcription and expression of neurotrophin-related genes.

Structural characterization and evaluation of antioxidant, anticancer and hypoglycemic activity of radiation degraded oat (Avena sativa) β- glucan

NASA Astrophysics Data System (ADS)

Hussain, Peerzada R.; Rather, Sarver A.; Suradkar, Prashant P.

2018-03-01

Oat β-D-glucan after extraction was degraded at doses of 3, 6, 9, 12 and 15 kGy. The average molecular weight decreased to 45 kDa at dose of 15 kGy from an initial value of 200 kDa in native sample. XRD analysis revealed no significant change in diffraction pattern of irradiated samples when compared with control, except a decrease in intensity of x-ray diffraction. The results of the antioxidant activity revealed decrease in EC50 values and corresponding increase in antioxidant activity of radiation degraded oat β-D-glucan. Results of the anticancer studies indicated that cytotoxicity of gamma irradiated oat β-D-glucan in cancer cell lines was highest against colo-205 and MCF7 cancer cells compared to T47D cell and no cytotoxicity was observed in normal cell lines at all concentrations used. Evaluation of hypoglycemic activity showed highest inhibition in α-glucosidase activity compared to α-amylase activity due to gamma irradiation of oat β-D-glucan. Comparison of the EC50 values of known standards and gamma irradiated oat beta-glucan samples indicates that radiation treatment significantly modified the biological activity of the beta-glucan samples. Therefore, it is suggested that gamma irradiation can be used for producing low molecular weight oat β-D-glucan; which can help in modifying the biological activities.

Prediction of beta-turns from amino acid sequences using the residue-coupled model.

PubMed

Guruprasad, K; Shukla, S

2003-04-01

We evaluated the prediction of beta-turns from amino acid sequences using the residue-coupled model with an enlarged representative protein data set selected from the Protein Data Bank. Our results show that the probability values derived from a data set comprising 425 protein chains yielded an overall beta-turn prediction accuracy 68.74%, compared with 94.7% reported earlier on a data set of 30 proteins using the same method. However, we noted that the overall beta-turn prediction accuracy using probability values derived from the 30-protein data set reduces to 40.74% when tested on the data set comprising 425 protein chains. In contrast, using probability values derived from the 425 data set used in this analysis, the overall beta-turn prediction accuracy yielded consistent results when tested on either the 30-protein data set (64.62%) used earlier or a more recent representative data set comprising 619 protein chains (64.66%) or on a jackknife data set comprising 476 representative protein chains (63.38%). We therefore recommend the use of probability values derived from the 425 representative protein chains data set reported here, which gives more realistic and consistent predictions of beta-turns from amino acid sequences.

Effects of transcutaneous electrical stimulation (1 pulse/sec) through custom-made disposable surface electrodes covering Omura's ST36 area of both legs on normal cell telomeres, oncogen C-fosAb2, integrin alpha5beta1, chlamydia trachomatis, etc. in breast cancer & alzheimer patients.

PubMed

Omura, Yoshiaki; Chen, Yemeng; Lermand, Olivia; Jones, Marilyn; Duvvi, Harsha; Shimotsuura, Yasuhiro

2010-01-01

Our previous study indicated that when extremely reduced normal cell (NC) telomeres in various cancer patients are increased over 500 ng BDORT units, abnormally high cancer cell telomeres and cancer-related markers such as Oncogen C-fosAb2 (Onco.)& Integrin alpha5beta1 (Integ.), & 8-OH-dG as well as bacterial & viral infections, mercury, asbestos, chromium, & beta-amyloid (1-42) markedly reduced due to improved circulation & excretion of these substances in urine. Since 1995, we have been using press-needle stimulation of Omura's ST36 with 200x press-release procedure 4x a day, with significant improvements in various cancer patients. In this study, Transcutaneous Electrical Stimulation (TES) at 60 pulses/min, which is close to patient's heart rate, was given between Omura's ST36 of both legs of the breast cancer & Alzheimer's patients. After about 10 minutes of TES, NC telomeres increased from 1 yg (= 10-24 g) to 500-525 ng; Integ. reduced from 85-75 ng to 0.5 ng & Chlamydia trachomatis (CT) reduced from 4500-3500 ng to 0.5 ng. An additional 10 minutes TES increased NC telomeres to 800-875 ng, while Integ. reduced to 0.5 yg & CT became less than 0.1 yg. After a total 30 minutes of TES, NC telomeres increased to 1000-1200ng BDORT units, with decreases in Integ. and Onco. to less than 0.1 yg. CT reduced to < 0.1 yg. About 24 hours later, NC telomeres were still 300 ng & both Integ. and Onco. were 2.5 ng. CT was approximately 20 ng. In Alzheimer patient, abnormally high beta-Amyloid (1-42) of 7-12 ng markedly reduced to within normal value of less than 1.5 ng by 20-30 min TES. Stimulation beyond 30 minutes gradually reduced NC telomeres. TES pulse rate of 4 pulses/sec for the same patient initially increased NC telomere up to 750-950 ng BDORT units within 20 minutes, but when stimulation continued more than 20 min, NC telomeres rapidly reduced to -150 ng in less than 10 min of TES with reduced beneficial effects.

Studies on human urinary arylamidases

NASA Technical Reports Server (NTRS)

Raina, P. N.; Ellis, S.

1975-01-01

Human urinary protein was found to contain enzymes that hydrolyze leucyl-, alanyl-, and glycyl-prolyl-beta-naphthylamides. The kinetic constants of these enzymes were determined and their chemical properties studied. The pH optima for the hydrolysis of the various naphthylamides were also determined. Glycyl-prolyl-arylaminade was inhibited by Co(2+) and Mn(2+), while two other arylamidases were slightly activated by Co(2+). p-Chloromercuriphenyl-sulfonate and puromycin significantly inhibited leucyl and alanyl arylamidases. The mean values for 24-hour urinary output for leucyl-, alanyl-, and glycyl-prolyl arylamidases in normal human male subjects were 4.32, 9.97, and 2.2 units, respectively.

Which routine test for kidney function?

PubMed Central

Parkin, A; Smith, H C; Brocklebank, J T

1989-01-01

Eighty measurements of plasma creatinine concentration, height:creatinine ratio, and plasma beta 2 microglobulin concentration were made on 72 children (age 4 months-18.5 years) with known renal disease. Results were compared with simultaneous measurements of glomerular filtration rate using plasma clearance of 51Cr edetic acid to assess the performance of each test as an initial screening procedure of renal insufficiency. Height:creatinine index less than 2.1 was found to have a higher sensitivity and predictive value of a normal result than the other tests and is therefore the preferred test for a screening procedure. PMID:2510609

Prospective validation of first-trimester combined screening for trisomy 21.

PubMed

Kagan, K O; Etchegaray, A; Zhou, Y; Wright, D; Nicolaides, K H

2009-07-01

To examine the performance of the new algorithm in screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). This was a prospective screening study for trisomy 21 in singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation using an algorithm combining maternal age, fetal NT thickness based on the mixture model for the assessment of NT, and maternal serum free beta-hCG and PAPP-A based on a multiple regression model for the assessment of serum biochemistry. The NT measurements were performed by 60 operators who had obtained The Fetal Medicine Foundation certificate of competence in the 11-13-week scan. The study population consisted of 19 614 pregnancies with a normal karyotype or delivery of a phenotypically normal baby (euploid group) and 122 cases of trisomy 21. In the euploid fetuses the NT was above the previously defined 50(th), 95(th) and 99(th) centiles in 10 033 (51.2%), 618 (3.2%) and 123 (0.6%) cases and the respective values for trisomy 21 were 117 (95.9%), 94 (77.0%) and 57 (46.7%). The median fetal NT was within 0.1 mm of the expected in 47 (78.3%) of the 60 sonographers and within 0.2 mm in all. In the euploid fetuses the median free beta-hCG was 1.0 (range, 0.1-29.4) multiples of the median (MoM) and the median PAPP-A was 1.0 (range, 0.2-3.3) MoM. The median MoM values were 1.0 or close to 1.0 MoM for each subgroup of pregnancy characteristics, including gestations of 11, 12 and 13 weeks, maternal weight of < 60 kg, 60-80 kg and > 80 kg, different ethnic origins, cigarette smokers and non-smokers, natural conception and in vitro fertilization. For a false-positive rate of 3%, the detection rate of trisomy 21 in screening by maternal age and fetal NT was 81% (95% CI, 73-89%), by maternal age and maternal serum biochemistry it was 63% (95% CI, 56-72%) and by combined screening based on maternal age, fetal NT and maternal serum biochemistry it was 90% (95% CI, 84-96%). This study has validated the new risk algorithm and demonstrated that in combined screening for trisomy 21 based on maternal age, fetal NT and free beta-hCG and PAPP-A the detection rate is about 90% for a 3% false-positive rate. (c) 2009 ISUOG.

[Beta-endorphin--physiologic role and menstrual cycle disorders].

PubMed

Meczekalski, B; Warenik-Szymankiewicz, A

1995-10-01

There are three classes of endogenous opioid peptides: endorphins, enkephalins, dynorphins. Beta-endorphin is the main representative of endogenous opioid peptides. Beta-endorphin plays a role in the regulation of the normal menstrual cycle and possibly in the onset of puberty. This peptide is also involved in the pathophysiology of such menstrual disorders as: exercise-associated amenorrhoea, stress-induced amenorrhoea, weight loss related amenorrhoea and premenstrual syndrome. Probable mechanism is that alterations in the levels of beta-endorphin may change the pulsatile release of GnRH. This article reviews contemporary views on the role of beta-endorphin in the physiology and disorders of the menstrual cycle.

New insights into the dual role of TGF-beta | Center for Cancer Research

Cancer.gov

The dual role of TGF-beta in cancer continues to challenge investigators in the field. TGF-beta is a well-known factor associated with tumor suppression in normal cells and yet promotes tumor progression in advanced stages of cancer. For years, the mechanisms that underpin this conundrum have not been fully understood. Ying Zhang, Ph.D., senior investigator in the Laboratory of Cellular and Molecular Biology, has been exploring this problem by examining and characterizing several key molecules in the TGF-beta signaling pathway. Read more…

The role of transforming growth factor-beta in PEG-rHuMGDF-induced reversible myelofibrosis in rats.

PubMed

Yanagida, M; Ide, Y; Imai, A; Toriyama, M; Aoki, T; Harada, K; Izumi, H; Uzumaki, H; Kusaka, M; Tokiwa, T

1997-12-01

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 microg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6-8 d followed by gradual decreases to control levels at 10-20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6-8 d, the levels of transforming growth factor-beta1 (TGF-beta1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7- and 2-fold, respectively. The elevated levels of TGF-beta1 were gradually reduced to baseline levels at 13-20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 microg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-beta1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.

Consumption of both resistant starch and beta-glucan improves postprandial plasma glucose and insulin in women.

PubMed

Behall, Kay M; Scholfield, Daniel J; Hallfrisch, Judith G; Liljeberg-Elmståhl, Helena G M

2006-05-01

Consumption of a meal high in resistant starch or soluble fiber (beta-glucan) decreases peak insulin and glucose concentrations and areas under the curve (AUCs). The objective was to determine whether the effects of soluble fiber and resistant starch on glycemic variables are additive. Ten normal-weight (43.5 years of age, BMI 22.0 kg/m2) and 10 overweight women (43.3 years of age, BMI 30.4 kg/m2) consumed 10 tolerance meals in a Latin square design. Meals (1 g carbohydrate/kg body wt) were glucose alone or muffins made with different levels of soluble fiber (0.26, 0.68, or 2.3 g beta-glucan/100 g muffin) and three levels of resistant starch (0.71, 2.57, or 5.06 g/100 g muffin). Overweight subjects had plasma insulin concentrations higher than those of normal-weight subjects but maintained similar plasma glucose levels. Compared with low beta-glucan-low resistant starch muffins, glucose and insulin AUC decreased when beta-glucan (17 and 33%, respectively) or resistant starch (24 and 38%, respectively) content was increased. The greatest AUC reduction occurred after meals containing both high beta-glucan-high resistant starch (33 and 59% lower AUC for glucose and insulin, respectively). Overweight women were somewhat more insulin resistant than control women. Soluble fiber appears to have a greater effect on postprandial insulin response while glucose reduction is greater after resistant starch from high-amylose cornstarch. The reduction in glycemic response was enhanced by combining resistant starch and soluble fiber. Consumption of foods containing moderate amounts of these fibers may improve glucose metabolism in both normal and overweight women.

Specific radioimmunoassay for human. beta. -lipotropin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeffcoate, W.J.; Rees, L.H.; Lowry, P.J.

1978-07-01

A homologous RIA for human ..beta..-lipotropin (..beta..hLPH) has been developed. At a final dilution of 1:24,000, the antiserum employed shows cross-reaction with ..beta..hLPH but none with human ..beta..-MSH (..beta..hMSH), and it is concluded that the antigenic determinant lies within the N-terminal 1 to 36 region of ..beta..hLPH. With extraction of 3-ml plasma samples, the assay is sufficiently sensitive to measure circulating ..beta..hLPH levels in normal individuals at 0900 h (25 to 200 pg/ml). There is a circadian variation with levels falling to (less than 20 to 80 pg/ml) at 2300 h. ..beta..hLPH levels rise after metyrapone and after insulin-induced hypoglycemia,more » and fall after administration of dexamethasone. In patients with a variety of diseases of the pituitary-adrenal axis, levels of ..beta..hLPH follow immunoreactive ACTH levels, although the two are not always secreted on a 1:1 molar basis.« less

Anemia of chronic disease is the more frequent type of anemia seen in patients with chronic idiopathic neutropenia of adults.

PubMed

Papadaki, H A; Eliopoulos, D G; Valatas, V; Eliopoulos, G D

2001-04-01

This study describes the frequency and the type of anemia seen in patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). We found that NI-CINA patients had low hemoglobin levels and increased serum concentrations of erythropoietin (EPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). The hemoglobin levels correlated positively with the number of circulating neutrophils and inversely with the levels of EPO and TNF-alpha but not of IL-1beta. Anemia, defined as the reduction of the hemoglobin below 12.0 g/dl for women and 13.3 g/dl for men, was found in 23 out of 148 patients studied, a proportion of 15.5%. Two of the anemic patients had iron deficiency anemia (8.7%), 11 had anemia of chronic disease (ACD; 47.8%) presenting with normal or slightly reduced erythrocytic indices, low serum iron, and increased serum ferritin, and the remaining ten had anemia of undefined pathogenesis (AUP; 43.5%) with normal or slightly decreased erythrocytic indices, serum iron ranging from 43 to 88 microg/dl, and ferritin values ranging from 12 to 50 ng/ml. We conclude that ACD is the more frequent type of anemia seen in patients with NI-CINA, and that pro-inflammatory cytokines, notably TNF-alpha, may be involved in the pathogenesis of both ACD and AUP, given that serum levels of the cytokine were significantly increased and that the EPO response to anemia was blunted in these patients. These findings further support our previously reported suggestion for the possible existence, in NI-CINA patients, of an unrecognized low-grade chronic inflammatory process that may be involved in the pathogenesis of the disorder.

Non-specific filtering of beta-distributed data.

PubMed

Wang, Xinhui; Laird, Peter W; Hinoue, Toshinori; Groshen, Susan; Siegmund, Kimberly D

2014-06-19

Non-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methylation is measured as a proportion, bounded between 0 and 1, with variance a function of the mean. Filtering on standard deviation biases the selection of probes to those with mean values near 0.5. We explore the effect this has on clustering, and develop alternate filter methods that utilize a variance stabilizing transformation for Beta distributed data and do not share this bias. We compared results for 11 different non-specific filters on eight Infinium HumanMethylation data sets, selected to span a variety of biological conditions. We found that for data sets having a small fraction of samples showing abnormal methylation of a subset of normally unmethylated CpGs, a characteristic of the CpG island methylator phenotype in cancer, a novel filter statistic that utilized a variance-stabilizing transformation for Beta distributed data outperformed the common filter of using standard deviation of the DNA methylation proportion, or its log-transformed M-value, in its ability to detect the cancer subtype in a cluster analysis. However, the standard deviation filter always performed among the best for distinguishing subgroups of normal tissue. The novel filter and standard deviation filter tended to favour features in different genome contexts; for the same data set, the novel filter always selected more features from CpG island promoters and the standard deviation filter always selected more features from non-CpG island intergenic regions. Interestingly, despite selecting largely non-overlapping sets of features, the two filters did find sample subsets that overlapped for some real data sets. We found two different filter statistics that tended to prioritize features with different characteristics, each performed well for identifying clusters of cancer and non-cancer tissue, and identifying a cancer CpG island hypermethylation phenotype. Since cluster analysis is for discovery, we would suggest trying both filters on any new data sets, evaluating the overlap of features selected and clusters discovered.

Rest-activity rhythm and sleep characteristics associated with depression symptom severity in strained dementia caregivers.

PubMed

Smagula, Stephen F; Krafty, Robert T; Taylor, Briana J; Martire, Lynn M; Schulz, Richard; Hall, Martica H

2017-12-01

Depression is associated with disturbances to sleep and the 24-h sleep-wake pattern (known as the rest-activity rhythm: RAR). However, there remains a need to identify the specific sleep/RAR correlates of depression symptom severity in population subgroups, such as strained dementia caregivers, who are at elevated risk for major depressive disorder. We assessed the cross-sectional associations of sleep/RARs with non-sleep depression symptom severity among 57 (mean age: 74 years, standard deviation: 7.4) strained dementia caregivers who were currently without clinical depression. We derived sleep measures from polysomnography and actigraphy, modelled RARs using a sigmoidally transformed cosine curve and measured non-sleep depression symptom severity using the Hamilton Depression Rating Scale (HRDS) with sleep items removed. The following sleep-wake measures were associated with greater depression symptom severity (absolute Spearman's correlations ranged from 0.23 to 0.32): more time awake after sleep onset (WASO), higher RAR middle level (mesor), relatively shorter active periods (alpha), earlier evening settling time (down-mesor) and less steep RARs (beta). In multivariable analysis, high WASO and low RAR beta were associated independently with depression symptom severity. Predicted non-sleep HDRS means (95% confidence intervals) in caregivers with and without these characteristics were: normal WASO/beta = 3.7 (2.3-5.0), high WASO/normal beta = 5.5 (3.5-7.6), normal WASO/low beta = 6.3 (3.6-8.9) and high WASO/low beta = 8.1 (5.3-10.9). Thus, in our sample of strained caregivers, greater sleep fragmentation (WASO) and less sustained/sharply segregated resting and active periods (low RAR beta) correlate uniquely with depression symptom severity. Longitudinal studies are needed to establish whether these independent sleep-wake correlates of depression symptoms explain heightened depression risk in dementia caregivers. © 2017 European Sleep Research Society.

Pharmacological characterization of the inhibitory activity of beta h-endorphin (beta h-EP), [Arg9,19,24,28,29]-beta h-EP, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, in the neuroeffector junction of the mouse vas deferens.

PubMed

Valenzuela, R; Li, C H; Huidobro-Toro, J P

1991-08-01

The inhibitory opioid activities of beta h-endorphin (beta h-EP), its structurally related peptide analogues [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 (Gly-Gly-beta h-EP), [Arg9,19,24,28,29]-beta h-EP (Arg-beta h-EP) and methionine enkephalin have been examined in the electrically stimulated mouse vas deferens bioassay. All four peptides behaved as full agonists; methionine enkephalin was the most potent followed by Arg-beta h-EP, beta h-EP and Gly-Gly-beta h-EP. Neither Gly-Gly-beta h-EP nor Arg-beta h-EP antagonized the inhibitory action of beta h-EP or methionine enkephalin. An hour of tissue exposure to 30 nM beta-funaltrexamine followed by thorough washing, displaced to the right, in a parallel fashion, the concentration-response curves of beta h-EP and analogues. Whereas the displacement of the concentration response curves was 8 to 10-fold for beta h-EP and Arg-beta h-EP, it was only about 3-fold for Gly-Gly-beta h-EP and methionine enkephalin. Naltrindole was the most potent antagonist of methionine enkephalin with an apparent pA2 of 9.4; its potency as an antagonist of beta h-EP and related analogues was approximately one-tenth of this with pA2 values approximately 8.5. Norbinaltorphimine also antagonized the action of the opioid peptides with pA2 values close to 7.8.

Comparative evaluation of hepatoprotective activity of carotenoids of microalgae.

PubMed

Murthy, K N Chidambara; Rajesha, J; Swamy, M Mahadeva; Ravishankar, G A

2005-01-01

The present study deals with evaluation of the hepatotoprotective activity of carotenoids from two well-known microalgae, Spirulina platensis and Dunaliella salina. Carotenoids were extracted in hexane:isopropyl alcohol (1:1 vol/vol) and fed orally in olive oil to Wistar albino rats at a dose of 100 microg/kg of body weight/day (in terms of carotenoids). The degree of hepatoprotection was measured by estimation of biochemical parameters like serum transaminases [serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT)], serum alkaline phosphatase, total albumin, and total protein. The results were compared with those for a control group, a CCl4-induced hepatic damage group, and a group treated with synthetic beta-carotene (all-trans) at the same dose. The protein content of the CCl4-treated group, which received normal diet and a dose of toxin, showed a significant decrease, i.e., 3.92 mg/mL, whereas the protein levels were higher, i.e., 6.96 and 6.32 mg/mL, in the case of the Dunaliella and Spirulina, respectively, carotenoid-treated groups. The CCl4-treated group shown higher activity of transaminases (128.68 units/mL SGPT and 171.52 units/mL SGOT). However, the activity of SGPT was 62.83 units/mL for Dunaliella and 76.83 units/mL for Spirulina, i.e., carotenoids of Dunaliella showed a higher degree of protection. For serum alkaline phosphatase, the standard beta-carotene value was 81.52 units/mL, compared with 84.46 units/mL for the CCl4-treated group; however, natural algal carotenoids yielded 38.45 units/mL (D. salina) and 44.73 units/mL (Spirulina). The total albumin value diminished with CCl4 treatment (2.46 mg/mL); the effect was highest for Dunaliella, followed by the Spirulina carotenoid-treated group. The results clearly indicate that carotenoids from Dunaliella possess better hepatoprotection compared with those from Spirulina. High-performance liquid chromatography of the carotenoids indicated that Spirulina contains only beta-carotene and Dunaliella contains other carotenoids and xanthophyll. The increase in protection with Dunaliella indicates that mixed carotenoids exhibit better biological activity than beta-carotene alone. The results of this study indicate that carotenoids obtained from an algal source have a higher antihepatotoxic effect, compared with synthetic beta-carotene and with beta-carotene alone from a natural source.

Antidiabetic Evaluation of Momordica charantia L Fruit Extracts

PubMed Central

Tahira, S; Hussain, F

2014-01-01

To investigate hypoglycaemic, hypolipidaemic and pancreatic beta cell regeneration activities of Momordica charantia L fruits (MC). Alloxan-induced diabetic rabbits were treated with methanolic and ethanolic MC extract. Effects of plant extracts and the drug glibenclamide on serum glucose, lipid profile and pancreatic beta cell were determined after two weeks of treatment. Serum glucose and lipid profiles were assayed by kit methods. Pancreatic tissue histopathology was performed to study pancreatic beta cell regeneration. Momordica charantia extracts produced significant hypoglycaemic effects (p < 0.05). Hypolipidaemic activity of MC was negligible. Momordica charantia supplementations were unable to normalize glucose and lipid profiles. Glibenclamide, a standard drug, not only lowered hyperglycaemia and hyperlipidaemia but also restored the normal levels. Regeneration of pancreatic beta cells by MC extracts was minimal, with fractional improvement produced by glibenclamide. The most significant finding of the present study was a 28% reduction in hyperglycaemia by MC ethanol extracts. To determine reliable antidiabetic potentials of MC, identification of the relevant antidiabetic components and underlying mechanisms is warranted. PMID:25429471

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liebhaber, S.A.; Weiss, I.; Cash, F.E.

Synthesis of normal human hemoglobin A, {alpha}{sub 2}{beta}{sub 2}, is based upon balanced expression of genes in the {alpha}-globin gene cluster on chromosome 15 and the {beta}-globin gene cluster on chromosome 11. Full levels of erythroid-specific activation of the {beta}-globin cluster depend on sequences located at a considerable distance 5{prime} to the {beta}-globin gene, referred to as the locus-activating or dominant control region. The existence of an analogous element(s) upstream of the {alpha}-globin cluster has been suggested from observations on naturally occurring deletions and experimental studies. The authors have identified an individual with {alpha}-thalassemia in whom structurally normal {alpha}-globin genesmore » have been inactivated in cis by a discrete de novo 35-kilobase deletion located {approximately}30 kilobases 5{prime} from the {alpha}-globin gene cluster. They conclude that this deletion inactivates expression of the {alpha}-globin genes by removing one or more of the previously identified upstream regulatory sequences that are critical to expression of the {alpha}-globin genes.« less

Stability analysis of the high poloidal bet scenario on DIII-Dtowards operation athigher plasma current

NASA Astrophysics Data System (ADS)

Guo, W. F.; Gong, X. Z.; Huang, J.; Ren, Q. L.; Qian, J. P.; Ding, S. Y.; Pan, C. K.; Li, G. Q.; Xia, T. Y.; Garofalo, A. M.; Lao, L.; Hyatt, A.; Ferron, J.; Meneghini, O.; Liu, Y. Q.; McClenaghan, J.; Holcomb, C. T.

2017-10-01

The high poloidal beta scenario with plasma current IP 600 kA and large-radius internal transport barrier (ITB) on DIII-D is subject to n =1 MHD kink modes when the current profile becomes very broad at internal inductance values li 0.5-0.6. It is desirable to extend this scenario to higer plasma current ( 1 MA) for highernormalized fusionperformance. However, higher current at constant normalized beta, ?N 3, would reducethe poloidal bet, ?P, below the threshold for ITB sustainment, observed at ?P 1.9. Thus, to avoid loss of the IT, ?N?? must be increased together with IP while avoiding the kink instability. MHD analysis is presented that explains possible paths to high ?N stability limit for the kink mode in tis scenario. Work supported by National Magnetic Confinement Fusion Program of Chin under 2015GB110001 and 2015GB102000 - National Natural Science Foundation of China under Grant No. 1147521 and by US DOE under DE-FC02-04ER54698.

The beta2- and beta3-adrenoceptor-mediated relaxation induced by fenoterol in guinea pig taenia caecum.

PubMed

Akimoto, Yurie; Horinouchi, Takahiro; Tanaka, Yoshio; Koike, Katsuo

2002-10-01

Fenoterol, a beta2-adrenoceptor selective agonist, belongs to the arylethanolamine class. To understand the receptor subtypes responsible for beta-adrenoceptor-mediated relaxation of guinea pig taenia caecum, we investigated the effect of fenoterol. Fenoterol caused concentration-dependent relaxation of the guinea pig taenia caecum. Propranolol, bupranolol and butoxamine produced shifts of the concentration-response curve for fenoterol. Schild regression analyses carried out for propranolol, butoxamine and bupranolol against fenoterol gave pA2 values of 8.41, 6.33 and 8.44, respectively. However, in the presence of 3 x 10(-4) M atenolol, 10(-4) M butoxamine and 10(-6) M phentolamine to block the beta1-, beta2- and a-adrenoceptor effects, respectively, Schild regression analysis carried out for bupranolol against fenoterol gave pA2 values of 5.80. These results suggest that the relaxant response to fenoterol in the guinea pig taenia caecum is mediated by both the beta2- and the beta3-adrenoceptors.

Pituitary resistance to thyroid hormone associated with a base mutation in the hormone-binding domain of the human 3,5,3'-triiodothyronine receptor-beta.

PubMed

Sasaki, S; Nakamura, H; Tagami, T; Miyoshi, Y; Nogimori, T; Mitsuma, T; Imura, H

1993-05-01

Point mutations in the human T3 receptor-beta (TR beta) gene causing single amino acid substitutions have been identified in several different kindreds with generalized resistance to thyroid hormone. Until now, no study has been reported on the TR gene in cases of pituitary resistance (PRTH). In the present study, we analyzed the TR beta gene in a 30-yr-old Japanese female with PRTH. She exhibited clinical features of hyperthyroidism, elevated serum thyroid hormone levels accompanied by inappropriately increased secretion of TSH, mildly elevated basal metabolic rate, and increased urinary excretion of hydroxyproline. No pituitary tumor was detected. DNA fragments of exons 3-8 of the genomic TR beta gene were generated by the polymerase chain reaction and analyzed by a single stranded conformation polymorphism method. Exon 7 of the patient's TR beta gene showed an abnormal band, suggesting the existence of mutation(s). By subcloning and sequencing the DNA, a point mutation was identified in one allele at nucleotide 1297 (C to T), which altered the 333rd amino acid, arginine, to tryptophan. Neither of her apparently normal parents had any mutations of the TR beta gene. In vitro translation products of the mutant TR beta gene showed remarkably decreased T3-binding activity (Ka, 2.1 x 10(8) M-1; normal TR beta Ka, 1.1 x 10(10) M-1). Since the molecular defect detected in a patient with PRTH is similar to that seen in subjects with generalized resistance to thyroid hormone, both types of the syndrome may represent a continuous spectrum of the same etiological defect with variable tissue resistance to thyroid hormone.

Augmented cell survival in eutopic endometrium from women with endometriosis: Expression of c-myc, TGF-beta1 and bax genes

PubMed Central

Johnson, M Cecilia; Torres, Marisa; Alves, Alessandra; Bacallao, Ketty; Fuentes, Ariel; Vega, Margarita; Boric, M Angélica

2005-01-01

Background Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside of the uterus. The fragments in normal menstruation are composed of necrotic and living cells, which do not survive in ectopic locations because of programmed cell death. The aim of this study was to evaluate if the balance between cell proliferation and apoptosis is changed in eutopic endometrium from women with endometriosis throughout the menstrual cycle by studying bax (pro-apoptotic), c-myc (regulator of cell cycle) and TGF-beta1 (involved in cell differentiation) genes. Methods Eutopic endometrium was obtained from: 30 women with endometriosis (32.8 +/- 5 years) and 34 fertile eumenorrheic women (36 +/- 5.3 years). We analyzed apoptosis (TUNEL: DNA fragmentation); cell proliferation (immunohistochemistry (IHC) for Ki67); c-myc, bax and TGF-beta1 mRNA abundance (RT-PCR) and TGF-beta1 protein (IHC) in endometrial explants. Results Cell proliferation strongly decreased from proliferative to late secretory phases in glands, but not in stroma, in both endometria. Positive staining in glands and stroma from proliferative endometrium with endometriosis was 1.9- and 2.2-fold higher than control endometrium, respectively (p < 0.05). Abundance of c-myc mRNA was 65% higher in proliferative endometrium from endometriosis than normal tissue (p < 0.05). TGF-beta1 (mRNA and protein) augmented during mid secretory phase in normal endometrium, effect not observed in endometrium with endometriosis. In normal endometrium, the percentage of apoptotic epithelial and stromal cells increased more than 30-fold during late secretory phase. In contrast, in endometrium from endometriosis, not only this increase was not observed, besides bax mRNA decreased 63% versus normal endometrium (p < 0.05). At once, in early secretory phase, apoptotic stromal cells increased 10-fold with a concomitant augment of bax mRNA abundance (42%) in endometria from endometriosis (p < 0.05). Conclusion An altered expression of c-myc, TGF-beta1 and bax was observed in eutopic endometrium from endometriosis, suggesting its participation in the regulation of cell survival in this disease. The augmented cell viability in eutopic endometrium from these patients as a consequence of a reduction in cell death by apoptosis, and also an increase in cell proliferation indicates that this condition may facilitate the invasive feature of the endometrium. PMID:16150151

Three mouse models of human thalassemia.

PubMed Central

Martinell, J; Whitney, J B; Popp, R A; Russell, L B; Anderson, W F

1981-01-01

Three types of mice with globin gene mutations, called 352HB, 27HB, and Hbath-J, appear to be true animal models of human thalassemia. Expression of the alpha-globin genes in three stocks of mice, each one heterozygous for one of the alpha-globin mutations, was examined at the polypeptide, RNA, and DNA levels. alpha-Globin polypeptide chains, relative to beta-globin chains in heterozygous thalassemic mice, are present at approximately 80% of normal. The ratios of alpha-globin to beta-globin RNA sequences are also 75-80% of normal, exactly reflecting the alpha-globin to beta-globin chain ratios. In the case of mutant 352HB, at least one alpha-globin gene is deleted. Thalassemic mouse erythroid cells appear to compensate partially for the loss of half of their alpha-globin genes. Images PMID:6946454

Probability density function of non-reactive solute concentration in heterogeneous porous formations.

PubMed

Bellin, Alberto; Tonina, Daniele

2007-10-30

Available models of solute transport in heterogeneous formations lack in providing complete characterization of the predicted concentration. This is a serious drawback especially in risk analysis where confidence intervals and probability of exceeding threshold values are required. Our contribution to fill this gap of knowledge is a probability distribution model for the local concentration of conservative tracers migrating in heterogeneous aquifers. Our model accounts for dilution, mechanical mixing within the sampling volume and spreading due to formation heterogeneity. It is developed by modeling local concentration dynamics with an Ito Stochastic Differential Equation (SDE) that under the hypothesis of statistical stationarity leads to the Beta probability distribution function (pdf) for the solute concentration. This model shows large flexibility in capturing the smoothing effect of the sampling volume and the associated reduction of the probability of exceeding large concentrations. Furthermore, it is fully characterized by the first two moments of the solute concentration, and these are the same pieces of information required for standard geostatistical techniques employing Normal or Log-Normal distributions. Additionally, we show that in the absence of pore-scale dispersion and for point concentrations the pdf model converges to the binary distribution of [Dagan, G., 1982. Stochastic modeling of groundwater flow by unconditional and conditional probabilities, 2, The solute transport. Water Resour. Res. 18 (4), 835-848.], while it approaches the Normal distribution for sampling volumes much larger than the characteristic scale of the aquifer heterogeneity. Furthermore, we demonstrate that the same model with the spatial moments replacing the statistical moments can be applied to estimate the proportion of the plume volume where solute concentrations are above or below critical thresholds. Application of this model to point and vertically averaged bromide concentrations from the first Cape Cod tracer test and to a set of numerical simulations confirms the above findings and for the first time it shows the superiority of the Beta model to both Normal and Log-Normal models in interpreting field data. Furthermore, we show that assuming a-priori that local concentrations are normally or log-normally distributed may result in a severe underestimate of the probability of exceeding large concentrations.

Superconducting Prototype Cavities for the Spallation Neutron Source (SNS) Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

G. Ciovati; P. Kneisel; K. Davis

2002-06-01

The Spallation Neutron Source project includes a superconducting linac section in the energy range from 186 MeV to 1000 MeV operating at a frequency of 805 MHz at 2.1 K. For this energy range two types of cavities are needed with geometrical Beta-values of Beta=0.61 and Beta=0.81. An aggressive cavity prototyping program is being pursued at JLab, which calls for fabricating and testing of four Beta=0.61 cavities and two Beta=0.81 cavities. Both types consist of six cells made from high purity niobium and feature one HOM coupler of the TESLA type on each beam pipe and a port for amore » high power coaxial input coupler. Three of the four Beta=0.61 cavities will be used for a cryomodule test in early 2002. At this time, four medium beta cavities and one high beta cavity have been completed and tested at JLab. In addition, the three medium beta cavities for the prototype cryomodule have been equipped with the integrated Ti-Helium vessel, successfully retested and will be assembled into a cavity string. Results from the cryo-module test should be available by the time of the conference. The tests on the Beta=0.61 cavity and the Beta=0.81 cavity exceeded the design values for gradient and Q - value: E{sub acc} =10.1 MV/m and Q = 5 x 10{sup 9} at 2.1K for Beta=0.61 and E{sub acc} = 12.3 MV/m and Q=5 x 10{sup 9} at 2.1K for Beta = 0.81. The medium beta cavities reached gradients between E{sub acc} = 15 MV/m and 21 MV/m. This paper will describe the test results obtained with the various cavities, some aspects of the HOM damping at cryogenic temperatures, results from microphonics and Lorentz force detuning tests and the cavity string assembly at the time of this workshop.« less

Contribution of beta 1- and beta 2-adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (-)-atenolol.

PubMed Central

Lemoine, H.; Schönell, H.; Kaumann, A. J.

1988-01-01

1. (-)-Atenolol was used as a tool to assess the function of beta 1- and beta 2-adrenoceptors in human heart. Right atrial and left ventricular preparations from patients undergoing open heart surgery were set up to contract isometrically. Membrane particles were prepared for beta-adrenoceptor labelling with [3H]-(-)-bupranolol and adenylate cyclase assays. 2. The positive inotropic effects of (-)-noradrenaline were antagonized to a similar extent by (-)-atenolol in atrial and ventricular preparations. (-)-Atenolol consistently antagonized the effects of (-)-adrenaline to a lesser extent than those of (-)-noradrenaline in atrial preparations. In ventricular preparations (-)-atenolol antagonized the effects of low concentrations of (-)-adrenaline to a lesser extent than those of high concentrations. 3. pKB values (M) of (-)-atenolol, estimated with non-linear analysis from the blockade of the positive inotropic effects of the catecholamines, were 7.4 for beta 1-adrenoceptors and 6.0 for beta 2-adrenoceptors. 4. (-)-Atenolol inhibited the binding of [3H]-(-)-bupranolol to ventricular beta 1-adrenoceptors with a pKD (M) of 5.9 and to ventricular beta 2-adrenoceptors with a pKD of 4.6. 5. (-)-Atenolol inhibited the catecholamine-induced adenylate cyclase stimulation in the atrium and ventricle with pKB values of 5.8-6.4 for beta 1- and pKB values of 4.7-5.7 for beta 2-adrenoceptors. The binding and cyclase assays suggest a partial affinity loss for (-)-atenolol inherent to membrane preparations. 6. beta 1-Adrenoceptors mediate the maximum positive inotropic effects of (-)-noradrenaline in both the atrium and ventricle of man. beta 2-Adrenoceptors appear to be capable of mediating maximal positive inotropic effects of (-)-adrenaline in atrium. In contrast, ventricular beta 2-adrenoceptors mediated only submaximal effects of (-)-adrenaline. PMID:2851354

Inverse expression of estrogen receptor-beta and nuclear factor-kappaB in urinary bladder carcinogenesis.

PubMed

Kontos, Stylianos; Kominea, Athina; Melachrinou, Maria; Balampani, Eleni; Sotiropoulou-Bonikou, Georgia

2010-09-01

To investigate the expression of nuclear factor-kappaB (NF-kappaB) and estrogen receptor-beta (ER-beta) signalling pathways in bladder urothelial carcinoma according to clinicopathological features, in order to elucidate their role during carcinogenesis. Immunohistochemical methodology was carried out on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females) who underwent transurethral resection of bladder neoplasms. Correlations between ER-beta and NF-kappaB, and tumor grade and T-stage were evaluated, along with demographic data, sex and age. A significant decrease in ER-beta expression in the nucleus of bladder cells during loss of cell differentiation (r(s) = -0.61, P-value < 0.001, test of trend P-value = 0.003) and in muscle invasive carcinomas (T2-T4; test of trend P-value < 0.001) was found. p65 Subunit of NF-kappaB was expressed in the nucleus and in the cytoplasm of bladder epithelial cells. A strong positive association between tumor grade and nuclear expression of NF-kappaB was shown. No correlation between NF-kappaB, nuclear or cytoplasmic staining, with T-stage was observed. An inverse correlation between ER-beta and nuclear p65 immunoreactivity was observed (r(s) = -0.45, P-value < 0.001). There was no correlation with demographic data. Our immunohistochemical study suggests the possible inverse regulation of NF-kappaB and ER-beta transcription factor during bladder carcinogenesis. Selective ER-beta agonists and agents, inhibitors of NF-kappaB, might represent a possible new treatment strategy for bladder urothelial tumors.

Pregnancy outcomes among women with beta-thalassemia trait.

PubMed

Charoenboon, Chitrakan; Jatavan, Phudit; Traisrisilp, Kuntharee; Tongsong, Theera

2016-04-01

To compare the obstetric outcomes between pregnant women affected by beta-thalassemia trait and normal controls. A retrospective cohort study was conducted on singleton pregnant women complicated by beta-thalassemia trait and normal controls, randomly selected with the controls-to-case ratio of 2:1. All were low-risk pregnancies without underlying medical diseases and fetal anomalies. The pregnancies undergoing invasive prenatal diagnosis were excluded. A total of 597 pregnant women with beta-thalassemia trait and 1194 controls were recruited. Baseline characteristics and maternal outcomes in the two groups were similar, except that hemoglobin levels were slightly lower in the study group. The prevalence of small for gestational age and preterm birth tended to be higher in the study group but not reached the significant levels but the rate of low birth weight was significantly higher in the study group (relative risk 1.25; 95 % CI 1.00-1.57). Additionally, abortion rate was also significantly higher in the study group (relative risk 3.25; 95 % CI 1.35-7.80). Beta-thalassemia trait could minimally, but significantly, increase risk of low birth weight but did not increase rates of maternal adverse outcomes.

Modifiable Risk Factors for Increased Arterial Stiffness in Outpatient Nephrology

PubMed Central

Elewa, Usama; Fernandez-Fernandez, Beatriz; Alegre, Raquel; Sanchez-Niño, Maria D.; Mahillo-Fernández, Ignacio; Perez-Gomez, Maria Vanessa; El-Fishawy, Hussein; Belal, Dawlat; Ortiz, Alberto

2015-01-01

Arterial stiffness, as measured by pulse wave velocity (PWV), is an independent predictor of cardiovascular events and mortality. Arterial stiffness increases with age. However, modifiable risk factors such as smoking, BP and salt intake also impact on PWV. The finding of modifiable risk factors may lead to the identification of treatable factors, and, thus, is of interest to practicing nephrologist. We have now studied the prevalence and correlates of arterial stiffness, assessed by PWV, in 191 patients from nephrology outpatient clinics in order to identify modifiable risk factors for arterial stiffness that may in the future guide therapeutic decision-making. PWV was above normal levels for age in 85/191 (44.5%) patients. Multivariate analysis showed that advanced age, systolic BP, diabetes mellitus, serum uric acid and calcium polystyrene sulfonate therapy or calcium-containing medication were independent predictors of PWV. A new parameter, Delta above upper limit of normal PWV (Delta PWV) was defined to decrease the weight of age on PWV values. Delta PWV was calculated as (measured PWV) - (upper limit of the age-adjusted PWV values for the general population). Mean±SD Delta PWV was 0.76±1.60 m/sec. In multivariate analysis, systolic blood pressure, active smoking and calcium polystyrene sulfonate therapy remained independent predictors of higher delta PWV, while age, urinary potassium and beta blocker therapy were independent predictors of lower delta PWV. In conclusion, arterial stiffness was frequent in nephrology outpatients. Systolic blood pressure, smoking, serum uric acid, calcium-containing medications, potassium metabolism and non-use of beta blockers are modifiable factors associated with increased arterial stiffness in Nephrology outpatients. PMID:25880081

Effect of delayed toxicity of chemical barriers to control Argentine ants (Hymenoptera: Formicidae).

PubMed

Soeprono, Andrew M; Rust, Michael K

2004-12-01

Brief exposures of Argentine ants to four different insecticide treatments, bifenthrin, beta-cyfluthrin, bifenthrin + beta-cyfluthrin, and fipronil, were conducted to determine Kaplan-Meier product limit survivorship percentiles (SPs) at 21-23 and 27-29 degrees C. Bifenthrin, beta-cyfluthrin, and bifenthrin + beta-cyfluthrin provided rapid kill at 21-23 degrees C with SP10 values ranging from 11.2 to 33.7 min. Fipronil provided delayed toxicity at 21-23 degrees C with SP10 values ranging from 270 to 960 min. At 27-29 degrees C, all of the SP10 values significantly decreased. Field tests in which Argentine ants were induced to forage across insecticide-treated surfaces were used to determine the effect that speed of action has on foraging and recruitment ability, and whether these insecticides are repellent. The slower-acting fipronil allowed a greater amount of foraging and consequently a greater fraction of the colony to be exposed, whereas fast-acting bifenthrin, beta-cyfluthrin, and bifenthrin + beta-cyfluthrin inhibited recruitment, resulting in fewer ants being exposed and killed. Implications for controlling ants by using perimeter barrier treatments are discussed.

Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence.

PubMed

Fernandez-Mendoza, Julio; Li, Yun; Vgontzas, Alexandros N; Fang, Jidong; Gaines, Jordan; Calhoun, Susan L; Liao, Duanping; Bixler, Edward O

2016-05-01

To examine whether insomnia is associated with spectral electroencephalographic (EEG) dynamics in the beta (15-35Hz) range during sleep in an adolescent general population sample. A case-control sample of 44 adolescents from the Penn State Child Cohort underwent a 9-h polysomnography, clinical history and physical examination. We examined low-beta (15-25 Hz) and high-beta (25-35 Hz) relative power at central EEG derivations during sleep onset latency (SOL), sleep onset (SO), non-rapid eye movement (NREM) sleep, and wake after sleep onset (WASO). Compared to controls (n = 21), individuals with insomnia (n = 23) showed increased SOL and WASO and decreased sleep duration and efficiency, while no differences in sleep architecture were found. Insomniacs showed increased low-beta and high-beta relative power during SOL, SO, and NREM sleep as compared to controls. High-beta relative power was greater during all sleep and wake states in insomniacs with short sleep duration as compared to individuals with insomnia with normal sleep duration. Adolescent insomnia is associated with increased beta EEG power during sleep, which suggests that cortical hyperarousal is present in individuals with insomnia as early as adolescence. Interestingly, cortical hyperarousal is greatest in individuals with insomnia with short sleep duration and may explain the sleep complaints of those with normal sleep duration. Disturbed cortical networks may be a shared mechanism putting individuals with insomnia at risk of psychiatric disorders. © 2016 Associated Professional Sleep Societies, LLC.

Radiation leukemia virus-induced thymic lymphomas express a restricted repertoire of T-cell receptor V beta gene products.

PubMed Central

Sen-Majumdar, A; Weissman, I L; Hansteen, G; Marian, J; Waller, E K; Lieberman, M

1994-01-01

We have investigated the phenotypic changes that take place during the process of neoplastic transformation in the thymocytes of C57BL/Ka mice infected by the radiation leukemia virus (RadLV). By the combined use of antibodies against the envelope glycoprotein gp70 of RadLV, the transformation-associated cell surface marker 1C11, and the CD3-T-cell receptor (TCR) complex, we found that in the RadLV-infected thymus, the earliest expression of viral gp70 is in 1C11hi cells; a small but significant percentage of these cells also express CD3. A first wave of viral replication, manifested by the expression of high levels of gp70 in thymocytes (over 70% positive), reaches a peak at 2 weeks; during this period, no significant changes are observed in the expression of 1C11 or CD3. The population of gp70+ cells is drastically reduced at 3 to 4 weeks after infection. However, a second cohort of gp70+ cells appears after 4 weeks, and these cells express high levels of 1C11 and TCR determinants as well. RadLV-induced lymphomas differ from normal thymocytes in their CD4 CD8 phenotype, with domination by one or more subsets. Characterization of TCR gene rearrangements in RadLV-induced lymphomas shows that most of these tumors are clonal or oligoclonal with respect to the J beta 2 TCR gene, while the J beta 1 TCR gene is rearranged in a minority (4 of 11) of lymphomas. TCR V beta repertoire analysis of 12 tumors reveals that 6 (50%) express exclusively the V beta 6 gene product, 2 (17%) are V beta 5+, and 1 (8%) each are V beta 8+ and V beta 9+. In normal C57BL/Ka mice, V beta 6 is expressed on 12%, V beta 5 is expressed on 9%, V beta 8 is expressed on 22%, and V beta 9 is expressed on 4% of TCRhi thymocytes. Thus, it appears that RadLV-induced thymic lymphomas are not randomly selected with respect to expressed TCR V beta type. Images PMID:8289345

A novel NADP(+)-dependent dehydrogenase activity for 7alpha/beta- and 11beta-hydroxysteroids in human liver nuclei: A third 11beta-hydroxysteroid dehydrogenase.

PubMed

Robinzon, B; Prough, R A

2009-06-15

Human tissue from uninvolved liver of cancer patients was fractionated using differential centrifugation and characterized for 11betaHSD enzyme activity against corticosterone, dehydrocorticosterone, 7alpha- and 7beta-hydroxy-dehydroepiandrosterone, and 7-oxo-dehydroepiandrosterone. An enzyme activity was observed in nuclear protein fractions that utilized either NADP(+) or NAD(+), but not NADPH and NADH, as pyridine nucleotide cofactor with K(m) values of 12+/-2 and 390+/-2microM, compared to the K(m) for microsomal 11betaHSD1 of 43+/-8 and 264+/-24microM, respectively. The K(m) for corticosterone in the NADP(+)-dependent nuclear oxidation reaction was 102+/-16nM, compared to 4.3+/-0.8microM for 11betaHSD1. The K(cat) values for nuclear activity with NADP(+) was 1687nmol/min/mg/micromol, compared to 755nmol/min/mg/micromol for microsomal 11betaHSD1 activity. Inhibitors of 11betaHSD1 decreased both nuclear and microsomal enzyme activities, suggesting that the nuclear activity may be due to an enzyme similar to 11betaHSD Type 1 and 2.

5Beta,6beta-epoxy-17-oxoandrostan-3beta-yl acetate and 5beta,6beta-epoxy-20-oxopregnan-3beta-yl acetate.

PubMed

Pinto, Rui M A; Salvador, Jorge A R; Paixão, José A

2008-05-01

In the title compounds, C(21)H(30)O(4), (I), and C(23)H(34)O(4), (II), respectively, which are valuable intermediates in the synthesis of important steroid derivatives, rings A and B are cis-(5beta,10beta)-fused. The two molecules have similar conformations of rings A, B and C. The presence of the 5beta,6beta-epoxide group induces a significant twist of the steroid nucleus and a strong flattening of the B ring. The different C17 substituents result in different conformations for ring D. Cohesion of the molecular packing is achieved in both compounds only by weak intermolecular interactions. The geometries of the molecules in the crystalline environment are compared with those of the free molecules as given by ab initio Roothan Hartree-Fock calculations. We show in this work that quantum mechanical ab initio methods reproduce well the details of the conformation of these molecules, including a large twist of the steroid nucleus. The calculated twist values are comparable, but are larger than the observed values, indicating a possible small effect of the crystal packing on the twist angles.

Hb taradale [beta82(EF6)Lys-->Arg]: a novel mutation at a 2,3-diphosphoglycerate binding site.

PubMed

Brennan, Stephen O; Sheen, Campbell; Chan, Tim; George, Peter M

2005-01-01

Hb Taradale [beta82(EF6)Lys-->Arg] was initially detected as a split Hb A0 peak on Hb A1c, monitoring. Red cell parameters, hemoglobin (Hb) electrophoresis and stability tests were normal. Mass spectrometry (ms) clearly identified a variant beta chain with a mass increase of 28 Da and peptide mapping located the mutation site to peptide betaT-9. DNA sequencing confirmed the presence of a novel beta82(EF6)Lys-->Arg mutation. This conservative substitution at a 2,3-diphosphoglycerate (2,3-DPG) binding site did not, however, appear to affect the P50 for oxygen binding.

[Glucocorticoid pathway mediated the inhibition of testosterone in rats exposed to dibutyl phthalate].

PubMed

Zhang, Xiao-feng; Zheng, Jing; Li, Zi; Zhang, Yang

2009-08-01

To investigate the inhibitory mechanisms of testosterone (T) biosynthesis in rats exposed to dibutyl phthalate (DBP). Male Wistar rats were randomly divided into five groups by weight, including 0.25, 0.50, 1.00, 2.00 g/kg DBP groups and corn oil control group, with 16 rats in each group. DBP was administered by gavage once a day. After 30 days exposure, eight rats in each group were killed and the others were killed after 15 days without DBP administration. The levels of T and glucocorticoid (GC) in serum were determined by radioimmunoassay. The expression levels of 11 beta-dedroxysteriod dehydrogenase (11 beta-HSD) mRNA and steroidogenesis acute regulatory protein (StAR) mRNA were determined by RT-PCR. The protein expression level of glucocorticoid receptor (GR) was investigated by Western blotting. During exposure period, in 1.00 and 2.00 g/kg DBP groups, the levels of T were (0.260 +/- 0.218) ng/ml and (0.260 +/- 0.342) ng/ml, the levels of GC were (13.470 +/- 5.661) ng/ml and (13.740 +/- 3.977) ng/ml, the levels of T and GC in control group were (1.045 +/- 1.222) ng/ml and (9.224 +/- 3.496) ng/ml. There were statistic differences between 1.00 and 2.00 g/kg DBP groups and control group (t(T) values were -2.295 and -2.295, t(GC) values were 2.159 and 2.296, respectively, P < 0.05). The expression level of StAR mRNA was significantly down-regulated in 1.00 and 2.00 g/kg DBP groups, while StAR/beta-Actin values were 0.657 +/- 0.060 and 0.407 +/- 0.033, and compared to control group (0.871 +/- 0.081), there was statistic difference (t values were -3.707 and -8.037, P < 0.05). In 1.00 and 2.00 g/kg DBP groups, the expression of 11 beta-HSD mRNA and the expression of GR protein were increased in DBP dose-dependent manner, while 11 beta-HSD/beta-Actin values were 0.538 +/- 0.138 and 0.988 +/- 0.133, and GR/beta-Actin were 0.785 +/- 0.106 and 0.956 +/- 0.076, respectively. There were statistic difference, as compared to the controls (0.285 +/- 0.106 and 0.275 +/- 0.035) (t(11 beta-HSD/beta-Actin) values were 2.829 and 7.860, t(GR/beta-Actin) values were 8.064 and 10.77, respectively, P < 0.05).Linear correlation and regression revealed that there were positive correlation between DBP dose and the expression levels of 11 beta-HSD mRNA and GR protein, with r values of 0.766 and 0.790, respectively. In post-exposure period, there were no statistic differences of all above index among DBP groups and control group. DBP might inhibit T production in rats through GR mediation.

On heat loading, novel divertors, and fusion reactors

NASA Astrophysics Data System (ADS)

Kotschenreuther, M.; Valanju, P. M.; Mahajan, S. M.; Wiley, J. C.

2007-07-01

The limited thermal power handling capacity of the standard divertors (used in current as well as projected tokamaks) is likely to force extremely high (˜90%) radiation fractions frad in tokamak fusion reactors that have heating powers considerably larger than ITER [D. J. Campbell, Phys. Plasmas 8, 2041 (2001)]. Such enormous values of necessary frad could have serious and debilitating consequences on the core confinement, stability, and dependability for a fusion power reactor, especially in reactors with Internal Transport Barriers. A new class of divertors, called X-divertors (XD), which considerably enhance the divertor thermal capacity through a flaring of the field lines only near the divertor plates, may be necessary and sufficient to overcome these problems and lead to a dependable fusion power reactor with acceptable economics. X-divertors will lower the bar on the necessary confinement to bring it in the range of the present experimental results. Its ability to reduce the radiative burden imparts the X-divertor with a key advantage. Lower radiation demands allow sharply peaked density profiles that enhance the bootstrap fraction creating the possibility for a highly increased beta for the same beta normal discharges. The X-divertor emerges as a beta-enhancer capable of raising it by up to roughly a factor of 2.

Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caselli, E.; Powers, R.A.; Blaszczak, L.C.

2010-03-05

Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well asmore » four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta}-lactamases. Surprisingly, there is little correlation between the affinity contributed by R1 side chains and their occurrence in {beta}-lactam inhibitors or {beta}-lactam substrates of serine {beta}-lactamases. Nevertheless, presented in acylglycineboronic acids, these side chains can lead to inhibitors with high affinities and specificities. The structures of their complexes with AmpC give a molecular context to their affinities and may guide the design of anti-resistance compounds in this series.« less

Incretin hormone receptors are required for normal beta cell development and function in female mice.

PubMed

Omar, Bilal; Ahlkvist, Linda; Yamada, Yuchiro; Seino, Yutaka; Ahrén, Bo

2016-05-01

The incretin hormones, glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), potentiate insulin secretion and are responsible for the majority of insulin secretion that occurs after a meal. They may also, however, have a fundamental role in pancreatic beta cell development and function, independently of their role in potentiating insulin secretion after a meal. This has led to observations that a loss of GIP or GLP-1 action affects normal beta cell function, however each one of the incretin hormones may compensate when the action of the other is lost and therefore the overall impact of the incretin hormones on beta cell function is not known. We therefore utilized a mouse line deficient in both the GLP-1 and GIP receptor genes, the double incretin receptor knockout (DIRKO), to determine the consequences of a lifelong, complete lack of incretin hormone action on beta cell function, in vivo, in intact animals. We found that DIRKO mice displayed impaired glucose tolerance and insulin secretion in response to both oral glucose and mixed meal tolerance tests compared to wild-type mice. Assessment of beta cell function using the hyperglycemic clamp technique revealed an 80% decrease in first phase insulin response in DIRKO mice, but a normal second phase insulin secretion. A similar decline was seen when wild-type mice were given acute intravenous injection of glucose together with the GLP-1 receptor antagonist Ex9-39. Ex vivo assessments of the pancreas revealed significantly fewer islets in the pancreata of DIRKO mice despite no differences in total pancreatic mass. Insulin secretion from isolated islets of DIRKO mice was impaired to a similar extent to that seen during the hyperglycemic clamp. Insulin secretion in wild-type islets was impaired by acute treatment with Ex9-39 to a similar extent as the in vivo intravenous glucose tolerance tests. In conclusion, a loss of the action of both incretin hormones results in direct impairment of beta cell function both in vivo and in vitro in a process that appears to be independent of the intestinally secreted incretin hormones. We therefore conclude that the incretin hormones together significantly impact both beta-cell function and beta-cell development. Copyright © 2016. Published by Elsevier Inc.

Superconducting Prototype Cavities for the Spallation Neutron Source (SNS) Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

G. Ciovati, P. Kneisel , J. Brawley, R. Bundy, I. Campisi, K. Davis; K. Macha; D. Machie

2001-09-01

The Spallation Neutron Source project includes a superconducting linac section in the energy range from 192 MeV to 1000 MeV, operating at a frequency of 805 MHz at 2.1 K. For this energy range two types of cavities are needed with geometrical beta - values of beta= 0.61 and beta= 0.81. An aggressive cavity prototyping program is being pursued at Jlab, which calls for fabricating and testing of four beta= 0.61 cavities and two beta= 0.81 cavities. Both types consist of six cells made from high purity niobium and feature one HOM coupler on each beam pipe and a portmore » for a high power coaxial input coupler. Three of the four beta= 0.61 cavities will be used for a cryomodule test in early 2002. At this time four medium beta cavities and one high beta cavity have been completed at JLab. The first tests on the beta=0.61 cavity and the beta= 0.81 exceeded the design values for gradient and Q - value: E{sub acc} = 1 0.3 MV/m and Q = 5 x 10{sup 9} at 2.1K for beta= 0.61 and E{sub acc} = 12.3 MV/m and Q = 5 x 10{sup 9} at 2.1K for beta= 0.81. One of the medium beta cavities has been equipped with an integrated helium vessel and measurements of the static and dynamic Lorentz force detuning will be done and compared to the ''bare'' cavities. In addition two single cell cavities have been fabricated, equipped with welded-on HOM couplers. They are being used to evaluate the HOM couplers with respect to multipacting, fundamental mode rejection and HOM damping as far as possible in a single cell. This paper will describe the cavity design with respect to electrical and mechanical features, the fabrication efforts and the results obtained with the different cavities existing at the time of this workshop.« less

[Changes of insulin resistance and islet beta cells function in subjects with high-normal blood pressure].

PubMed

Xu, Ling-Ling; Xiang, Hong-Ding; Zhang, Li-Hong; Chen, Wei; Fang, Jing-Hui

2009-08-01

To investigate the changes of insulin resistance and islet beta cells function in subjects with euglycemia and high-normal blood pressure. Total 423 subjects were divided into normal blood pressure group and high-normal blood pressure group. Body height, weight, waist and hip circumference, and biochemical data were measured. Homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISI)-composite, and first-phase (1 PH) Stumvoll index were calculated. Results Waist circumference, total cholesterol, triglyceride, low-density lipoprotein cholesterol, HOMA-IR were significantly higher and IPH Stumvoll index and ISI-composite were significantly lower in high-normal blood pressure group than in normal blood pressure group (P < 0.05). Systolic blood pressure (SBP) was positively correlated with HOMA-IR (r = 0.122) and negatively correlated with 1PH Stumvoll index (r = -0. 159) and ISI-composite (r = -0.131) (P < 0.05). SBP and triglyceride were independent factors for IPH Stumvoll index. Insulin resistance and islet dysfunction may exist in subjects with high-normal blood pressure.

Superconducting Prototype Cavities for the Spallation Neutron Source (SNS) Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peter Kneisel; John Brawley; Richard Bundy

2001-06-01

The Spallation Neutron Source project includes a superconducting linac section in the energy range from 192 MeV to 1000 MeV. For this energy range two types of cavities are needed with geometrical beta - values of beta = 0.61 and beta = 0.81. An aggressive cavity prototyping program is being pursued at Jlab, which calls for fabricating and testing of four beta = 0.61 cavities and two beta = 0.81 cavities. Both types consist of six cells made from high purity niobium and feature one HOM coupler of the TESLA type on each beam pipe and a port for amore » high power coaxial input coupler. Three of the four beta = 0.61 cavities will be used for a cryomodule test at the end of the year 2001. At this time two cavities of each type have been fabricated and the first tests on the beta = 0.61 cavity exceeded the design values for gradient and Q - value: Eacc = 10.3 MV/m and Q = 6.5 x 10{sup 9} at 2.1K. This paper will describe the cavity design with respect to electrical and mechanical features, the fabrication efforts and the results obtained with the different cavities existing at the time of the conference.« less

Dosimetry of radium-223 and progeny

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, D.R.; Sgouros, G.

Radium-223 is a short-lived (11.4 d) alpha emitter with potential applications in radioimmunotherapy of cancer. Radium-223 can be complexed and linked to protein delivery molecules for specific tumor-cell targeting. It decays through a cascade of short-lived alpha- and beta-emitting daughters with emission of about 28 MeV of energy through complete decay. The first three alpha particles are essentially instantaneous. Photons associated with Ra-223 and progeny provide the means for tumor and normal-organ imaging and dosimetry. Two beta particles provide additional therapeutic value. Radium-223 may be produced economically and in sufficient amounts for widescale application. Many aspects of the chemistry ofmore » carrier-free isotope preparation, complexation, and linkage to the antibody have been developed and are being tested. The radiation dosimetry of a Ra-223-labeled antibody shows favorable tumor to normal tissue dose ratios for therapy. The 11.4-d half-life of Ra-223 allows sufficient time for immunoconjugate preparation, administration, and tumor localization by carrier antibodies before significant radiological decay takes place. If 0.01 percent of a 37 MBq (1 mCi) injection deposits in a one gram tumor mass, and if the activity is retained with a typical effective half-time (75 h), the absorbed dose will be 163 mGy MBq{sup {minus}1} (600 rad mCi{sup {minus}1}) administered. 49 refs., 5 figs., 2 tabs.« less

Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis.

PubMed

Rubinstein, M; Mogil, J S; Japón, M; Chan, E C; Allen, R G; Low, M J

1996-04-30

A physiological role for beta-endorphin in endogenous pain inhibition was investigated by targeted mutagenesis of the proopiomelanocortin gene in mouse embryonic stem cells. The tyrosine codon at position 179 of the proopiomelanocortin gene was converted to a premature translational stop codon. The resulting transgenic mice display no overt developmental or behavioral alterations and have a normally functioning hypothalamic-pituitary-adrenal axis. Homozygous transgenic mice with a selective deficiency of beta-endorphin exhibit normal analgesia in response to morphine, indicating the presence of functional mu-opiate receptors. However, these mice lack the opioid (naloxone reversible) analgesia induced by mild swim stress. Mutant mice also display significantly greater nonopioid analgesia in response to cold water swim stress compared with controls and display paradoxical naloxone-induced analgesia. These changes may reflect compensatory upregulation of alternative pain inhibitory mechanisms.

Hb Potomac (101 Glu replaced by Asp): speculations on placental oxygen transport in carriers of high-affinity hemoglobins.

PubMed

Charache, S; Jacobson, R; Brimhall, B; Murphy, E A; Hathaway, P; Winslow, R; Jones, R; Rath, C; Simkovich, J

1978-02-01

Blood from a woman with unexplained erythrocytosis had increased oxygen affinity, but no abnormality could be detected by electrophoresis or chromatography of her hemolysate. Separation of the tryptic peptides of her beta chains disclosed two half-sized peaks in the regions of beta T-11. The faster of these was abnormal, with the structure beta 101 Glu replaced by Asp. The new hemoglobin was called "Potomac." Three of the proband's four surviving siblings and both of her children were carriers. Differences in the ratio of carrier: normal children born to male of female carriers of 23 other high-affinity hemoglobins were not significant. The high proportion of carriers in this kindred was probably due to chance alone, and not because high maternal oxygen affinity interfered with oxygen transport to fetuses with normal hemoglobin.

High internal inductance for steady-state operation in ITER and a reactor

DOE PAGES

Ferron, John R.; Holcomb, Christopher T.; Luce, Timothy C.; ...

2015-06-26

Increased confinement and ideal stability limits at relatively high values of the internal inductance (more » $${{\\ell}_{i}}$$ ) have enabled an attractive scenario for steady-state tokamak operation to be demonstrated in DIII-D. Normalized plasma pressure in the range appropriate for a reactor has been achieved in high elongation and triangularity double-null divertor discharges with $${{\\beta}_{\\text{N}}}\\approx 5$$ at $${{\\ell}_{i}}\\approx 1.3$$ , near the ideal $n=1$ kink stability limit calculated without the effect of a stabilizing vacuum vessel wall, with the ideal-wall limit still higher at $${{\\beta}_{\\text{N}}}>5.5$$ . Confinement is above the H-mode level with $${{H}_{98\\left(\\text{y},2\\right)}}\\approx 1.8$$ . At $${{q}_{95}}\\approx 7.5$$ , the current is overdriven, with bootstrap current fraction $${{f}_{\\text{BS}}}\\approx 0.8$$ , noninductive current fraction $${{f}_{\\text{NI}}}>1$$ and negative surface voltage. For ITER (which has a single-null divertor shape), operation at $${{\\ell}_{i}}\\approx 1$$ is a promising option with $${{f}_{\\text{BS}}}\\approx 0.5$$ and the remaining current driven externally near the axis where the electron cyclotron current drive efficiency is high. This scenario has been tested in the ITER shape in DIII-D at $${{q}_{95}}=4.8$$ , so far reaching $${{f}_{\\text{NI}}}=0.7$$ and $${{f}_{\\text{BS}}}=0.4$$ at $${{\\beta}_{\\text{N}}}\\approx 3.5$$ with performance appropriate for the ITER Q=5 mission, $${{H}_{89}}{{\\beta}_{\\text{N}}}/q_{95}^{2}\\approx 0.3$$ . Modeling studies explored how increased current drive power for DIII-D could be applied to maintain a stationary, fully noninductive high $${{\\ell}_{i}}$$ discharge. Lastly, stable solutions in the double-null shape are found without the vacuum vessel wall at $${{\\beta}_{\\text{N}}}=4$$ , $${{\\ell}_{i}}=1.07$$ and $${{f}_{\\text{BS}}}=0.5$$ , and at $${{\\beta}_{\\text{N}}}=5$$ with the vacuum vessel wall.« less

Quantitative Assessment of Proliferative Effects of Oral Vanadium on Pancreatic Islet Volumes and Beta Cell Numbers of Diabetic Rats

PubMed Central

Pirmoradi, Leila; Noorafshan, Ali; Safaee, Akbar; Dehghani, Gholam Abbas

2016-01-01

Background: Oral vanadyl sulfate (vanadium) induces normoglycemia, proliferates beta cells and prevents pancreatic islet atrophy in streptozotocin-induced diabetic rats. Soteriological method is used to quantitate the proliferative effects of vanadium on beta-cell numbers and islet volumes of normal and diabetic rats. Methods: Adult male Sprague-Dawley rats were made diabetic with intravenous streptozotocin injection (40 mg/kg). Normal and diabetic rats were divided into four groups. While control normal and diabetic (CD) groups used water, vanadium-treated normal (VTN) and diabetic (VTD) groups used solutions containing vanadyl sulfate (0.5-1 mg/mL, VOSO4+5H2O). Tail blood samples were used to measure blood glucose (BG) and plasma insulin. Two months after treatment, rats were sacrificed, pancreata prepared, and stereology method was used to quantitatively evaluate total beta cell numbers (TBCN) and total islet volumes (TISVOL). Results: Normoglycemia persisted in VTN with significantly decreased plasma insulin (0.190.08 vs. 0.970.27 ng/dL, P<0.002). The respective high BG (53249 vs. 14446 mg/dL, P<0.0001) and reduced plasma insulin (0.260.15 vs. 0.540.19 ng/dL, P<0.002) seen in CD were reversed in VTD during vanadium treatment or withdrawal. While the induction of diabetes, compared to their control, significantly decreased TISVOL (1.90.2 vs. 3.030.6 mm3, P<0.003) and TBCN (0.990.1 vs. 3.20.2 x 106, P<0.003), vanadium treatment significantly increased TISVOL (2.90.8 and 4.071.0 mm3, P<0.003) and TBCN (1.50.3 and 3.80.6 x 106, P<0.03). Conclusion: Two-month oral vanadium therapy in STZ-diabetic rats ameliorated hyperglycemia by partially restoring plasma insulin. This action was through proliferative actions of vanadium in preventing islet atrophy by increasing beta-cell numbers. PMID:26459400

Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sako, Takeo; Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047; Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017

2013-12-06

Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focusedmore » on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.« less

Beta-endorphin-induced inhibition and stimulation of insulin secretion in normal humans is glucose dependent.

PubMed

Giugliano, D; Cozzolino, D; Salvatore, T; Torella, R; D'Onofrio, F

1988-09-01

This study evaluated the effect of human beta-endorphin on pancreatic hormone levels and their responses to nutrient challenges in normal subjects. Infusion of 0.5 mg/h beta-endorphin caused a significant rise in plasma glucose concentrations preceded by a significant increase in peripheral glucagon levels. No changes occurred in the plasma concentrations of insulin and C-peptide. Acute insulin and C-peptide responses to intravenous pulses of different glucose amounts (0.33 g/kg and 5 g) and arginine (3 g) were significantly reduced by beta-endorphin infusion (P less than .01). This effect was associated with a significant reduction of the glucose disappearance rates, suggesting that the inhibition of insulin was of biological relevance. beta-Endorphin also inhibited glucose suppression of glucagon levels and augmented the glucagon response to arginine. To verify whether the modification of prestimulus glucose level could be important in these hormonal responses to beta-endorphin, basal plasma glucose concentrations were raised by a primed (0.5 g/kg) continuous (20 mg kg-1.min-1) glucose infusion. After stabilization of plasma glucose levels (350 +/- 34 mg/dl, t = 120 min), beta-endorphin infusion caused an immediate and marked increase in plasma insulin level (peak response 61 +/- 9 microU/ml, P less than .01), which remained elevated even after the discontinuation of opioid infusion. Moreover, the acute insulin response to a glucose pulse (0.33 g/kg i.v.) given during beta-endorphin infusion during hyperglycemia was significantly higher than the response obtained during euglycemia (171 +/- 32 vs. 41 +/- 7 microU/ml, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Role for transforming growth factor-beta1 in alport renal disease progression.

PubMed

Sayers, R; Kalluri, R; Rodgers, K D; Shield, C F; Meehan, D T; Cosgrove, D

1999-11-01

Alport syndrome results from mutations in either the alpha3(IV), alpha4(IV), or alpha5(IV) collagen genes. The disease is characterized by a progressive glomerulonephritis usually associated with a high-frequency sensorineural hearing loss. A mouse model for an autosomal form of Alport syndrome [collagen alpha3(IV) knockout] was produced and characterized. In this study, the model was exploited to demonstrate a potential role for transforming growth factor-beta1 (TGF-beta1) in Alport renal disease pathogenesis. Kidneys from normal and Alport mice, taken at different stages during the course of renal disease progression, were analyzed by Northern blot, in situ hybridization, and immunohistology for expression of TGF-beta1 and components of the extracellular matrix. Normal and Alport human kidney was examined for TGF-beta1 expression using RNase protection. The mRNAs encoding TGF-beta1 (in both mouse and human), entactin, fibronectin, and the collagen alpha1(IV) and alpha2(IV) chains were significantly induced in total kidney as a function of Alport renal disease progression. The induction of these specific mRNAs was observed in the glomerular podocytes of animals with advanced disease. Type IV collagen, laminin-1, and fibronectin were markedly elevated in the tubulointerstitium at 10 weeks, but not at 6 weeks, suggesting that elevated expression of specific mRNAs on Northern blots reflects events associated with tubulointerstitial fibrosis. The concomitant accumulation of mRNAs encoding TGF-beta1 and extracellular matrix components in the podocytes of diseased kidneys may reflect key events in Alport renal disease progression. These data suggest a role for TGF-beta1 in both glomerular and tubulointerstitial damage associated with Alport syndrome.

Renormalization of loop functions for all loops

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brandt, R.A.; Neri, F.; Sato, M.

1981-08-15

It is shown that the vacuum expectation values W(C/sub 1/,xxx, C/sub n/) of products of the traces of the path-ordered phase factors P exp(igcontour-integral/sub C/iA/sub ..mu../(x)dx/sup ..mu../) are multiplicatively renormalizable in all orders of perturbation theory. Here A/sub ..mu../(x) are the vector gauge field matrices in the non-Abelian gauge theory with gauge group U(N) or SU(N), and C/sub i/ are loops (closed paths). When the loops are smooth (i.e., differentiable) and simple (i.e., non-self-intersecting), it has been shown that the generally divergent loop functions W become finite functions W when expressed in terms of the renormalized coupling constant and multipliedmore » by the factors e/sup -K/L(C/sub i/), where K is linearly divergent and L(C/sub i/) is the length of C/sub i/. It is proved here that the loop functions remain multiplicatively renormalizable even if the curves have any finite number of cusps (points of nondifferentiability) or cross points (points of self-intersection). If C/sub ..gamma../ is a loop which is smooth and simple except for a single cusp of angle ..gamma.., then W/sub R/(C/sub ..gamma../) = Z(..gamma..)W(C/sub ..gamma../) is finite for a suitable renormalization factor Z(..gamma..) which depends on ..gamma.. but on no other characteristic of C/sub ..gamma../. This statement is made precise by introducing a regularization, or via a loop-integrand subtraction scheme specified by a normalization condition W/sub R/(C-bar/sub ..gamma../) = 1 for an arbitrary but fixed loop C-bar/sub ..gamma../. Next, if C/sub ..beta../ is a loop which is smooth and simple except for a cross point of angles ..beta.., then W(C/sub ..beta../) must be renormalized together with the loop functions of associated sets S/sup i//sub ..beta../ = )C/sup i//sub 1/,xxx, C/sup i//sub p/i) (i = 2,xxx,I) of loops C/sup i//sub q/ which coincide with certain parts of C/sub ..beta../equivalentC/sup 1//sub 1/. Then W/sub R/(S/sup i//sub ..beta../) = Z/sup i/j(..beta..)W(S/sup j//sub ..beta../) is finite for a suitable matrix Z/sup i/j(..beta..).« less

Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dudas, Jozsef, E-mail: Jozsef.Dudas@i-med.ac.at; Fullar, Alexandra, E-mail: fullarsz@gmail.com; 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest

2011-09-10

Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated withmore » IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the presence of SCC-25 tumor cells. IL1-{beta} receptor expression in fibroblasts, especially in CAFs represents a major option in coordination of fibroblast and tumor behavior. A key event in IL1-{beta} signaling, the phosphorylation of IRAK1, occurred in co-cultured fibroblasts, which has lead to nuclear translocation of NF{kappa}B{alpha}, and finally to induction of several genes, including BDNF, IRF1, IL-6 and COX-2. The most enhanced induction was found for IL-6 and COX-2.« less

A Synopsis of Factors Regulating Beta Cell Development and Beta Cell Mass

PubMed Central

Prasadan, Krishna; Shiota, Chiyo; Xiangwei, Xiao; Ricks, David; Fusco, Joseph; Gittes, George

2016-01-01

The insulin-secreting beta cells in the endocrine pancreas regulate blood glucose levels, and loss of functional beta cells leads to insulin deficiency, hyperglycemia (high blood glucose) and diabetes mellitus. Current treatment strategies for type-1 (autoimmune) diabetes are islet transplantation, which has significant risks and limitations, or normalization of blood glucose with insulin injections, which is clearly not ideal. The type-1 patients can lack insulin counter-regulatory mechanism; therefore, hypoglycemia is a potential risk. Hence, a cell-based therapy offers a better alternative for the treatment of diabetes. Past research was focused on attempting to generate replacement beta cells from stem cells, however, recently there has been an increasing interest in identifying mechanisms that will lead to the conversion of pre-existing differentiated endocrine cells into beta cells. The goal of this review is to provide an overview of several of the key factors that regulate new beta cell formation (neogenesis) and beta cell proliferation. PMID:27105622

Effect of electroacupuncture on the expression of interlukin-1beta mRNA after transient focal cerebral ischemia.

PubMed

Xu, Zhen-Feng; Wu, Gen-Cheng; Cao, Xiao-Ding

2002-01-01

It has been reported that interleukin-1beta (IL-1beta ) play a key role in the pathogenesis of cerebral ischemia. Acupuncture is an effective traditional medical therapy in China. The aim of present study was to evaluate the effect of electroacupuncture (EA) on IL-1beta mRNA expression after middle cerebral artery occlusion (MCAO) in rats. Using in situ hybridization technique, it was found that in the MCAO group the expression of IL-1beta mRNA was significantly increased at 2h, 6h, 12h after reperfusion in cerebral ischemic cortex compared with normal group. In EA+ MCAO group the expression of IL-1beta mRNA was significantly decreased at 2h, 6h and 12h in ischemic cortex compared with MCAO group. The results indicated that EA might decrease the IL-1beta protein expression by reducing the IL-beta mRNA expression in ischemic cortex.

The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation.

PubMed

Spencer, K; Ong, C Y; Liao, A W; Papademetriou, D; Nicolaides, K H

2000-08-01

In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21 we have shown a significant difference in the median MoM of the markers: fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a female fetus compared with a male fetus. For maternal serum free beta-hCG levels are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal fetuses are 10% higher in the presence of a female fetus and 13% higher if the fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in both chromosomally normal and trisomy 21 female fetuses. The consequence of such changes when screening for trisomy 21 will be a reduction in the detection rate in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal sex, however, is probably not feasible, since ultrasound detection of fetal sex is only 70-90% accurate in the 10-14 week period. Copyright 2000 John Wiley & Sons, Ltd.

A review and comparison of Bayesian and likelihood-based inferences in beta regression and zero-or-one-inflated beta regression.

PubMed

Liu, Fang; Eugenio, Evercita C

2018-04-01

Beta regression is an increasingly popular statistical technique in medical research for modeling of outcomes that assume values in (0, 1), such as proportions and patient reported outcomes. When outcomes take values in the intervals [0,1), (0,1], or [0,1], zero-or-one-inflated beta (zoib) regression can be used. We provide a thorough review on beta regression and zoib regression in the modeling, inferential, and computational aspects via the likelihood-based and Bayesian approaches. We demonstrate the statistical and practical importance of correctly modeling the inflation at zero/one rather than ad hoc replacing them with values close to zero/one via simulation studies; the latter approach can lead to biased estimates and invalid inferences. We show via simulation studies that the likelihood-based approach is computationally faster in general than MCMC algorithms used in the Bayesian inferences, but runs the risk of non-convergence, large biases, and sensitivity to starting values in the optimization algorithm especially with clustered/correlated data, data with sparse inflation at zero and one, and data that warrant regularization of the likelihood. The disadvantages of the regular likelihood-based approach make the Bayesian approach an attractive alternative in these cases. Software packages and tools for fitting beta and zoib regressions in both the likelihood-based and Bayesian frameworks are also reviewed.

Beyond low beta-decay Q values

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mustonen, M. T.; Suhonen, J.

Beta decays with low Q values can be utilized in the quest to determine the neutrino mass scale. This is being realized in two experiments, KATRIN and MARE, using tritium and {sup 187}Re, respectively. The beta-decay of {sup 187}Re had the lowest known Q value until 2005, when the beta decay of {sup 115}In to the first excited state of {sup 115}Sn was discovered in Gran Sasso underground laboratory. Last year two independent ion trap measurements confirmed that this decay breaks the former record by an order of magnitude.Our theoretical study on this tiny decay channel complemented the experimental effortmore » by the JYFLTRAP group in Finland and HADES underground laboratory in Belgium. A significant discrepancy between the experimental and theoretical results was found. This might be explained by various atomic contributions known to grow larger as the Q value decreases. However, the traditional recipes for taking these effects into account break down on this new ultra-low Q value regime, providing new challenges for theorists on the borderline between nuclear and atomic physics.« less

Designing Predictive Models for Beta-Lactam Allergy Using the Drug Allergy and Hypersensitivity Database.

PubMed

Chiriac, Anca Mirela; Wang, Youna; Schrijvers, Rik; Bousquet, Philippe Jean; Mura, Thibault; Molinari, Nicolas; Demoly, Pascal

Beta-lactam antibiotics represent the main cause of allergic reactions to drugs, inducing both immediate and nonimmediate allergies. The diagnosis is well established, usually based on skin tests and drug provocation tests, but cumbersome. To design predictive models for the diagnosis of beta-lactam allergy, based on the clinical history of patients with suspicions of allergic reactions to beta-lactams. The study included a retrospective phase, in which records of patients explored for a suspicion of beta-lactam allergy (in the Allergy Unit of the University Hospital of Montpellier between September 1996 and September 2012) were used to construct predictive models based on a logistic regression and decision tree method; a prospective phase, in which we performed an external validation of the chosen models in patients with suspicion of beta-lactam allergy recruited from 3 allergy centers (Montpellier, Nîmes, Narbonne) between March and November 2013. Data related to clinical history and allergy evaluation results were retrieved and analyzed. The retrospective and prospective phases included 1991 and 200 patients, respectively, with a different prevalence of confirmed beta-lactam allergy (23.6% vs 31%, P = .02). For the logistic regression method, performances of the models were similar in both samples: sensitivity was 51% (vs 60%), specificity 75% (vs 80%), positive predictive value 40% (vs 57%), and negative predictive value 83% (vs 82%). The decision tree method reached a sensitivity of 29.5% (vs 43.5%), specificity of 96.4% (vs 94.9%), positive predictive value of 71.6% (vs 79.4%), and negative predictive value of 81.6% (vs 81.3%). Two different independent methods using clinical history predictors were unable to accurately predict beta-lactam allergy and replace a conventional allergy evaluation for suspected beta-lactam allergy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Modulation of Neck Intermuscular Beta Coherence during Voice and Speech Production

ERIC Educational Resources Information Center

Stepp, Cara E.; Hillman, Robert E.; Heaton, James T.

2011-01-01

Purpose: The purpose of this study was to better understand neck intermuscular beta coherence (15-35 Hz; NIBcoh) in healthy individuals, with respect to modulation by behavioral tasks. Method: Mean NIBcoh was measured using surface electromyography at 2 anterior neck locations in 10 individuals during normal speech, static nonspeech maneuvers,…

An inversion of 25 base pairs causes feline GM2 gangliosidosis variant.

PubMed

Martin, Douglas R; Krum, Barbara K; Varadarajan, G S; Hathcock, Terri L; Smith, Bruce F; Baker, Henry J

2004-05-01

In G(M2) gangliosidosis variant 0, a defect in the beta-subunit of lysosomal beta-N-acetylhexosaminidase (EC 3.2.1.52) causes abnormal accumulation of G(M2) ganglioside and severe neurodegeneration. Distinct feline models of G(M2) gangliosidosis variant 0 have been described in both domestic shorthair and Korat cats. In this study, we determined that the causative mutation of G(M2) gangliosidosis in the domestic shorthair cat is a 25-base-pair inversion at the extreme 3' end of the beta-subunit (HEXB) coding sequence, which introduces three amino acid substitutions at the carboxyl terminus of the protein and a translational stop that is eight amino acids premature. Cats homozygous for the 25-base-pair inversion express levels of beta-subunit mRNA approximately 190% of normal and protein levels only 10-20% of normal. Because the 25-base-pair inversion is similar to mutations in the terminal exon of human HEXB, the domestic shorthair cat should serve as an appropriate model to study the molecular pathogenesis of human G(M2) gangliosidosis variant 0 (Sandhoff disease).

Subunit assembly of hemoglobin: an important determinant of hematologic phenotype.

PubMed

Bunn, H F

1987-01-01

Hemoglobin's physiologic properties depend on the orderly assembly of its subunits in erythropoietic cells. The biosynthesis of alpha- and beta-globin polypeptide chains is normally balanced. Heme rapidly binds to the globin subunit, either during translation or shortly thereafter. The formation of the alpha beta-dimer is facilitated by electrostatic attraction of a positively charged alpha-subunit to a negatively charged beta-subunit. The alpha beta-dimer dissociates extremely slowly. The difference between the rate of dissociation of alpha beta- and alpha gamma-dimers with increasing pH explains the well-known alkaline resistance of Hb F. Two dimers combine to form the functioning alpha 2 beta 2-tetramer. This model of hemoglobin assembly explains the different levels of positively charged and negatively charged mutant hemoglobins that are encountered in heterozygotes and the effect of alpha-thalassemia and heme deficiency states in modifying the level of the variant hemoglobin as well as Hb A2. Electrostatic interactions also affect the binding of hemoglobin to the cytoplasmic surface of the red cell membrane and may underlie the formation of target cells. Enhanced binding of positively charged variants such as S and C trigger a normally dormant pathway for potassium and water loss. Thus, the positive charge on beta c is responsible for the two major contributors to the pathogenesis of Hb SC disease: increased proportion of Hb S and increased intracellular hemoglobin concentration. It is likely that electrostatic interactions play an important role in the assembly of a number of other multisubunit macromolecules, including membrane receptors, cytoskeletal proteins, and DNA binding proteins.

Metabolic Stress and Compromised Identity of Pancreatic Beta Cells

PubMed Central

Swisa, Avital; Glaser, Benjamin; Dor, Yuval

2017-01-01

Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types. The loss of beta cell identity appears to be driven by glucotoxicity inhibiting the activity of key beta cell transcription factors including Pdx1, Nkx6.1, MafA and Pax6, thereby silencing beta cell genes and derepressing alternative islet cell genes. The loss of beta cell identity is at least partly reversible upon normalization of glycemia, with implications for the reversibility of T2D, although it is not known if beta cell failure reaches eventually a point of no return. In this review we discuss current evidence for metabolism-driven compromised beta cell identity, key knowledge gaps and opportunities for utility in the treatment of T2D. PMID:28270834

Metabolic Stress and Compromised Identity of Pancreatic Beta Cells.

PubMed

Swisa, Avital; Glaser, Benjamin; Dor, Yuval

2017-01-01

Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types. The loss of beta cell identity appears to be driven by glucotoxicity inhibiting the activity of key beta cell transcription factors including Pdx1, Nkx6.1, MafA and Pax6, thereby silencing beta cell genes and derepressing alternative islet cell genes. The loss of beta cell identity is at least partly reversible upon normalization of glycemia, with implications for the reversibility of T2D, although it is not known if beta cell failure reaches eventually a point of no return. In this review we discuss current evidence for metabolism-driven compromised beta cell identity, key knowledge gaps and opportunities for utility in the treatment of T2D.

Characterization of a beta 1----3-N-acetylglucosaminyltransferase associated with synthesis of type 1 and type 2 lacto-series tumor-associated antigens from the human colonic adenocarcinoma cell line SW403.

PubMed

Holmes, E H

1988-01-01

Previous studies have indicated that activation of a normally unexpressed beta 1----3-N-acetylglucosaminyltransferase is responsible for the accumulation of a wide diversity of both type 1 and 2 lacto-series antigens in human colonic adenocarcinomas. A beta 1----3-N-acetylglucosaminyltransferase has been solubilized from the human colonic adenocarcinoma cell line SW403 by 0.2% Triton X-100 and some of its properties have been studied. The enzyme was active over a broad pH range from 5.8 to 7.5 and had a strict requirement for Mn2+ as a divalent metal ion. Transfer of N-acetylglucosamine (GlcNAc) to lactosylceramide was optimal when assayed in the presence of a final concentration of Triton CF-54 of 0.3%. Inclusion of CDPcholine in the reaction mixture stimulated the activity by protecting the UDP[14C]GlcNAc from hydrolysis by endogenous enzymes. The kinetic parameters of the enzyme were studied. Km values for acceptors nLc4 and nLc6 were determined to be 0.19 mM for each. However, the Vmax values calculated for these acceptors were 150 and 110 pmol/h/mg protein for nLc4 and nLc6, respectively, suggesting reduced potential for further elongation as the chain length increases. The Km for UDPGlcNAc was determined to be 0.17 mM. Studies of the acceptor specificity have indicated transfer of GlcNAc occurs mainly to type 2 chain nonfucosylated structures. However, elongation of the type 1 chain structure Lc4 was also detected.

Exercise- and cold-induced changes in plasma beta-endorphin and beta-lipotropin in men and women.

PubMed

Viswanathan, M; Van Dijk, J P; Graham, T E; Bonen, A; George, J C

1987-02-01

The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response of men, eumenorrheic women, and amenorrheic women (n = 6) to 1 h of rest or to a bicycle ergometer test [20 min at 30% maximum O2 uptake (VO2max), 20 min at 60% VO2max, and at 90% VO2max to exhaustion] was studied in both normal (22 degrees C) and cold (5 degrees C) environments. beta-EP and beta-LPH was measured by radioimmunoassay in venous samples collected every 20 min during rest or after each exercise bout. Exhaustive exercise at ambient temperature (Ta) 22 degrees C induced significant increases in plasma beta-EP and beta-LPH in all subjects as did work at 60% VO2max in amenorrheic and eumenorrheic women. During work at Ta 5 degrees C, the relative increase in beta-EP and beta-LPH was suppressed in eumenorrheic women and completely prevented in amenorrheic women. Although significant lowering of beta-EP and beta-LPH was observed in men and eumenorrheic women during rest at 5 degrees C, amenorrheic women maintained precold exposure levels. These findings suggest that plasma beta-EP and beta-LPH may reflect a thermoregulatory response to heat load. There appears to be a sexual dimorphism in exercise- and cold-induced release of beta-EP and beta-LPH and amenorrhea may be accompanied by alterations in these responses.

Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency.

PubMed

Lutfallah, Chantal; Wang, Weihua; Mason, J Ian; Chang, Ying Tai; Haider, Anzar; Rich, Barry; Castro-Magana, Mariano; Copeland, Kenneth C; David, Raphael; Pang, Songya

2002-06-01

To define the hormonal criteria via genotypic proof for 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency in the adrenals and gonads, we investigated the type II 3beta-HSD genotype in 55 patients with clinical and/or hormonal presentation suggesting compromised adrenal with or without gonadal 3beta-HSD activity. Fourteen patients (11 males and 3 females) had ambiguous genitalia with or without salt wasting and with or without premature pubarche. One female neonate had salt wasting only. Twenty-five children (4 males and 21 females) had premature pubarche only. Fifteen adolescent and adult females had hirsutism with or without menstrual disorder. The type II 3beta-HSD gene, including the promoter region up to -1053 base, all exons I, II, III, IV, and exon and intron boundaries, was sequenced in all subjects. Eight patients had a proven or predictably deleterious mutation in both alleles of the type II 3beta-HSD gene, and 47 patients had no apparent mutation in the gene. ACTH-stimulated (1 h post iv bolus of 250 microg Cortrosyn) serum 17-hydroxypregnenolone (Delta5-17P) levels and basal and ACTH-stimulated ratios of Delta5-17P to cortisol (F) in the genotypic proven patients were unequivocally higher than those of age-matched or pubic hair stage matched genotype-normal patients or control subjects (n = 7-30 for each group). All other baseline and ACTH-stimulated hormone parameters, including dehydroepiandrosterone (DHEA) levels, ratios of Delta5-17P to 17-OHP and DHEA to androstenedione in the genotype-proven patients, overlapped with the genotype-normal patients or control subjects. The hormonal findings in the genotype-proven patients suggest that the following hormonal criteria are compatible with 3beta-HSD deficiency congenital adrenal hyperplasia (numeric and graphic reference standards from infancy to adulthood are provided): ACTH-stimulated Delta5-17P levels in 1) neonatal infants with ambiguous genitalia at or greater than 378 nmol/liter equivalent to or greater than 5.3 SD above the control mean level [95 +/- 53 (SD) nmol/liter]; 2) Tanner I children with ambiguous genitalia at or greater than 165 nmol/liter equivalent to or greater than 35 SD above the control mean level [12 +/- 4.3 (SD) nmol/liter]; 3) children with premature pubarche at or greater than 294 nmol/liter equivalent to or greater than 54 SD above Tanner II pubic hair stage matched control mean level [17 +/- 5 (SD) nmol/liter]; and 4) adults with at or greater than 289 nmol/liter equivalent to or greater than 21 SD above the normal mean level [25 +/- 12 (SD) nmol/liter]. ACTH-stimulated ratio of Delta5-17P to F in 1) neonatal infants at or greater than 434 equivalent to or greater than 6.4 SD above the control mean ratio [88 +/- 54 (SD)]; 2) Tanner I children at or greater than 216 equivalent to or greater than 23 SD above the control mean ratio [12 +/- 9 (SD)]; 3) children with premature pubarche at or greater than 363 equivalent to or greater than 38 SD above the control mean ratio [20 +/- 9 (SD)]; and 4) adults at or greater than 4010 equivalent to or greater than 221 SD above the normal mean ratio [29 +/- 18 (SD)]. Conversely, the hormonal data in the genotype-normal patients suggest the following hormonal criteria are not consistent with 3beta-HSD deficiency congenital adrenal hyperplasia: ACTH-stimulated Delta5-17P levels in children with premature pubarche up to 72 nmol/liter equivalent to up to 11 SD above the control mean level, and in hirsute females up to 150 nmol/liter equivalent to up to 12 SD above the normal female mean level [28 +/- 10 (SD) nmol/liter]; and ACTH-stimulated Delta5-17P to F ratio in children with premature pubarche up to 67 equivalent to up to 5 SD above the control mean ratio, and in hirsute females up to 151 equivalent to up to 10 SD above the normal mean ratio [32 +/- 12 (SD)]. These findings help define newly proposed hormonal criteria to accurately predict inherited 3beta-HSD deficiency.

Demonstration of interleukin-1 beta transcripts in acute myeloblastic leukemic cells by in situ hybridization.

PubMed

Nakamura, M; Kanakura, Y; Furukawa, Y; Ernst, T J; Griffin, J D

1990-07-01

The cells from some patients with acute myeloblastic leukemia will secrete autostimulatory cytokines in tissue culture without the addition of stimulators such as phorbol 12-myristate 13-acetate. Production of interleukin-1 beta (IL-1 beta), for example, has been observed in up to 50% of cases. In order to investigate the nature of the cell secreting IL-1 beta in AML, we used an antisense RNA probe to detect specific IL-1 beta transcripts in individual leukemic cells by in situ hybridization. In fresh, uncultured cells, IL-1 beta transcripts were observed in 1-40% of undifferentiated leukemic blast cells in 17 of 19 cases. In situ hybridization was at least as sensitive as Northern blot analysis in detecting IL-1 beta transcripts. No correlation of IL-1 beta transcript expression with FAB classification was observed. Normal blood and bone marrow mononuclear cells did not contain cells expressing IL-1 beta transcripts. These results support the concept that the regulation of cytokine genes in AML cells is aberrant.

GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells.

PubMed

Tran, Dat Q; Andersson, John; Wang, Rui; Ramsey, Heather; Unutmaz, Derya; Shevach, Ethan M

2009-08-11

TGF-beta family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-beta is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFbeta-binding protein (LTBP) to produce a large latent form. Latent TGF-beta is also found on the surface of activated FOXP3(+) regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-beta to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-beta and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-beta expression on activated Tregs and recombinant latent TGF-beta1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-beta on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism.

Soft epidermis of a scaleless snake lacks beta-keratin.

PubMed

Toni, M; Alibardi, L

2007-01-01

Beta-keratins are responsible for the mechanical resistance of scales in reptiles. In a scaleless crotalus snake (Crotalus atrox), large areas of the skin are completely devoid of scales, and the skin appears delicate and wrinkled. The epidermis of this snake has been assessed for the presence of beta-keratin by immunocytochemistry and immunoblotting using an antibody against chicken scale beta-keratin. This antibody recognizes beta-keratins in normal snake scales with molecular weights of 15-18 kDa and isoelectric points at 6.8, 7.5, 8.3 and 9.4. This indicates that beta-keratins of the stratum corneum are mainly basic proteins, so may interact with cytokeratins of the epidermis, most of which appear acidic (isoelectric points 4.5-5.5). A beta-layer and beta-keratin immunoreactivity are completely absent in moults of the scaleless mutant, and the corneous layer comprises a multi-layered alpha-layer covered by a flat oberhautchen. In conclusion, the present study shows that a lack of beta-keratins is correlated with the loss of scales and mechanical protection in the skin of this mutant snake.

Quantitative electroencephalogram (QEEG) Spectrum Analysis of Patients with Schizoaffective Disorder Compared to Normal Subjects.

PubMed

Moeini, Mahdi; Khaleghi, Ali; Amiri, Nasrin; Niknam, Zahra

2014-10-01

The aim of this study was to achieve a better understanding of schizoaffective disorder. Therefore, we obtained electroencephalogram (EEG) signals from patients with schizoaffective disorder and analyzed them in comparison to normal subjects. Forty patients with schizoaffective disorder and 40 normal subjects were selected randomly and their electroencephalogram signals were recorded based on 10-20 international system by 23 electrodes in open- and closed-eyes while they were sitting on a chair comfortably. After preprocessing for noise removal and artifact reduction, we took 60- second segments from each recorded signals. Then, the absolute and relative powers of these segments were evaluated in all channels and in 4 frequency bands (i.e., delta, theta, alpha and beta waves). Finally, Data were analyzed by independent t-test using SPSS software. A significant decrease in relative power in the alpha band, a significant decrease in power spectra in the alpha band and a significant increase in power spectra in the beta band were found in patients compared to normal subjects (P < 0.05). The predominant wave in the centro-parietal region was the beta wave in patients, but it was the alpha band in normal subjects (P = 0.048). Also, the predominant wave of the occipital region in patients was the delta wave, while it was the alpha wave in normal subjects (P = 0.038). Considering the findings, particularly based on the significant decrease of the alpha waves in schizoaffective patients, it can be concluded that schizoaffective disorder can be seen in schizophrenia spectrum.

A trait-based approach to community assembly: partitioning of species trait values into within- and among-community components.

PubMed

Ackerly, D D; Cornwell, W K

2007-02-01

Plant functional traits vary both along environmental gradients and among species occupying similar conditions, creating a challenge for the synthesis of functional and community ecology. We present a trait-based approach that provides an additive decomposition of species' trait values into alpha and beta components: beta values refer to a species' position along a gradient defined by community-level mean trait values; alpha values are the difference between a species' trait values and the mean of co-occurring taxa. In woody plant communities of coastal California, beta trait values for specific leaf area, leaf size, wood density and maximum height all covary strongly, reflecting species distributions across a gradient of soil moisture availability. Alpha values, on the other hand, are generally not significantly correlated, suggesting several independent axes of differentiation within communities. This trait-based framework provides a novel approach to integrate functional ecology and gradient analysis with community ecology and coexistence theory.

EI-2128-1, a novel interleukin-1beta converting enzyme inhibitor produced by Penicillium sp. E-2128.

PubMed

Koizumi, Fumito; Agatsuma, Tsutomu; Ando, Katsuhiko; Kondo, Hidemasa; Saitoh, Yutaka; Matsuda, Yuzuru; Nakanishi, Satoshi

2003-11-01

EI-2128-1, a novel interleukin-1beta converting enzyme (ICE) inhibitor, was isolated from the culture broths of Penicillium sp. E-2128. EI-2128-1 selectively inhibited human recombinant ICE activity with IC50 value of 0.59 microM, without inhibiting elastase and cathepsin B. EI-2128-1 also inhibited mature interleukin-1beta secretion from THP-1 cells induced by LPS with IC50 value of 0.28 microM.

Differences in cultural beliefs and values among African American and European American men with prostate cancer.

PubMed

Hughes Halbert, Chanita; Barg, Frances K; Weathers, Benita; Delmoor, Ernestine; Coyne, James; Wileyto, E Paul; Arocho, Justin; Mahler, Brandon; Malkowicz, S Bruce

2007-07-01

Although cultural values are increasingly being recognized as important determinants of psychological and behavioral outcomes following cancer diagnosis and treatment, empirical data are not available on cultural values among men. This study evaluated differences in cultural values related to religiosity, temporal orientation, and collectivism among African American and European American men. Participants were 119 African American and European American men who were newly diagnosed with early-stage and locally advanced prostate cancer. Cultural values were evaluated by self-report using standardized instruments during a structured telephone interview. After controlling for sociodemographic characteristics, African American men reported significantly greater levels of religiosity (Beta = 24.44, P < .001) compared with European American men. African American men (Beta = 6.30, P < .01) also reported significantly greater levels of future temporal orientation. In addition, men with more aggressive disease (eg, higher Gleason scores) (Beta = 5.11, P < .01) and those who were pending treatment (Beta = -6.42, P < .01) reported significantly greater levels of future temporal orientation. These findings demonstrate that while ethnicity is associated with some cultural values, clinical experiences with prostate cancer may also be important. This underscores the importance of evaluating the effects of both ethnicity and clinical factors in research on the influence of cultural values on cancer prevention and control.

Estimation of the initial slope of the cell survival curve after irradiation from micronucleus frequency in cytokinesis-blocked cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ono, K.; Masunaga, S.; Akaboshi, M.

1994-04-01

We have already reported that the {alpha}/{beta} ratio of the cell survival curve could be estimated from the micronucleus frequency in cytokinesis-blocked cells treated with cytochalasin-B after irradiation. In this paper, we investigate the direct relationship between the {alpha} value and the appearance of micronuclei. Cells of the SCCVII, RIF-1, EMT6, V-79, CHO, HeLa and human esophageal cancer cell lines were used for the study. Low-dose-rate irradiation was used to determine the {alpha} component of the relationship between dose and micronucleus frequency according to the linear-quadratic (LQ) model. A reduction of the dose rate from 3.09 to 0.0142 Gy/min correspondinglymore » decreased the micronucleus frequency; however, the fraction of binucleate cells without micronuclei was not affected in SCCVII and RIF-1 cells. When this fraction was defined as the normal nuclear division fraction, it decreased exponentially as a function of radiation dose. Then dose vs normal nuclear division fraction (NNDF) was fitted as follows: -In NNDF = aD + C, where D is radiation dose in grays and C is constant. The slope of the dose vs normal nuclear division fraction was not affected by dose rate. The correlation was also explored between the slope (a) and the {alpha} value of the cell survival curve determined by the colony formation assay in cells of eight cell lines. These two values showed extremely high agreement: {alpha} = 1.01a + 0.00795 (r = 0.99, P < 0.01). This assay was applied to estimate the {alpha} value of the cell survival curve of human esophageal cancer cell lines established from surgical specimens. 13 refs., 5 figs.« less

Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis.

PubMed Central

Rubinstein, M; Mogil, J S; Japón, M; Chan, E C; Allen, R G; Low, M J

1996-01-01

A physiological role for beta-endorphin in endogenous pain inhibition was investigated by targeted mutagenesis of the proopiomelanocortin gene in mouse embryonic stem cells. The tyrosine codon at position 179 of the proopiomelanocortin gene was converted to a premature translational stop codon. The resulting transgenic mice display no overt developmental or behavioral alterations and have a normally functioning hypothalamic-pituitary-adrenal axis. Homozygous transgenic mice with a selective deficiency of beta-endorphin exhibit normal analgesia in response to morphine, indicating the presence of functional mu-opiate receptors. However, these mice lack the opioid (naloxone reversible) analgesia induced by mild swim stress. Mutant mice also display significantly greater nonopioid analgesia in response to cold water swim stress compared with controls and display paradoxical naloxone-induced analgesia. These changes may reflect compensatory upregulation of alternative pain inhibitory mechanisms. Images Fig. 1 Fig. 2 PMID:8633004

[Clinical use of RU 486: control of the menstrual cycle and effect on the hypophyseal-adrenal axis].

PubMed

Gaillard, R C; Herrmann, W

1983-01-01

RU 486 is a synthetic 19 norsteroid with a great affinity for progesterone and glucocorticosteroid receptors. The antiprogesterone activity of RU 486 permits interruption of the luteal phase of the menstrual cycle and of early pregnancy, while the antiglucocorticosteroid activity interrupts the feedback mechanisms of cortisol at the hypothalamic-pituitary axis. 11 women aged 18-34 years who were 6-8 weeks pregnant were given daily doses of 200 mg of sensation of lipothymia. Blood pressure and laboratory test results remained normal. The daily increase of beta human chorionic gonadotropin (HCG) and progesterone was stopped by the antiprogesterone. It has been demonstrated in vitro that RU 486 inhibits secretion of beta HCG by cells of trophoblastic origin. 2 weeks after expulsion of the products of conception, the blood levels of beta HCG, progesterone, and estradiol had returned to nonpregnant values and ovarian activity was normal in women not using oral contraceptives. The reason for failure of expulsion in 2 cases was not known. RU 486 was also used to interrupt the luteal phase of normal menstrual cycles in 3 young women. 50 mg/day of RU 486 starting on the 22nd day was sufficient to induce bleeding within 48 hours. Studies using RU 486 50 mg/day beginning on the 10th cycle day indicate that progesterone plays a central and follicular role during the preovulatory period. The antiglucocorticosteroid activity of RU 486 was observed in pregnant women who received the abortifacient dose of 200 mg/day. The 8 a.m. plasma level of ACTH and beta-LPH cortisol remained elevated for thee 4 days of treatment. Nonpregnant women receiving 50 mg of RU 486 for 4 days beginning on the 22nd cycle day had no change in the level of hypophyseal-adrenal hormones.dd Tests in young male volunteers showed that RU 486 amplified circadian rhythms of the hypophysealadrenal axis, affecting specifically the morning hormonal levels without influencing afternoon levels. A test in which RU 486 was used to antagonize the inhibition producedd by dexamethasone during a test of suppression of the hypophyseal-adrenal axis confirmed that the antiglucocorticosteroid effect of RU 486 is produced at the level of the glucocorticosteroid receptors. The antiglucocorticosteroid effect is independent of the antiprogesterone effect. RU 486 may be utilizable in fertility control, to control undesirable effects of steroids in cases of hypercorticism, and perhaps eventually to test the hypophyseal-adrenal axis.

Polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns.

PubMed

Sipiläinen, R; Uusitupa, M; Heikkinen, S; Rissanen, A; Laakso, M

1997-01-01

Low basal metabolic rate (BMR) is a risk factor for weight gain and obesity. The polymorphism at codon 64 of the beta3-adrenergic receptor gene has been suggested to be associated with BMR. We investigated the frequency of the Trp64Arg of the beta3-adrenergic receptor gene and the effects of this polymorphism on BMR in obese Finns. Altogether, 170 obese subjects (29 men, 141 women, BMI 34.7 +/- 3.8 kg/m2, mean +/- SD) participated in the study. The frequency of the Trp64Arg polymorphism was 19%. None of the obese subjects were homozygous for the Arg-encoding allele. The frequency of the Trp64Arg polymorphism in obese Finns did not differ from nonobese and normoglycemic control subjects. BMR adjusted for lean body mass and age was lower in subjects with the Trp64Arg polymorphism (n = 20) than in normal homozygotes Trp64Trp (n = 99) (1,569 +/- 73 vs. 1,635 +/- 142 kcal/day, P = 0.004). For the female group (n = 98), the respective values were 1,501 +/- 66 kcal/day vs. 1,568 +/- 127 kcal/day (P = 0.004). There were no significant differences in weight, BMI, waist-to-hip ratio, lean body mass, percentage of fat, and respiratory quotient between the groups with or without the Trp64Arg polymorphism. Neither serum glucose nor insulin levels differed between the two groups. We conclude that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns but does not have significant effect on glucose metabolism.

Cyclic Adenosine Monophosphate Accumulation and beta-Adrenergic Binding in Unweighted and Denervated Rat Soleus Muscle

NASA Technical Reports Server (NTRS)

Kirby, Christopher R.; Woodman, Christopher R.; Woolridge, Dale; Tischler, Marc E.

1992-01-01

Unweighting, but not denervation, of muscle reportedly "spares" insulin receptors, increasing insulin sensitivity. Unweighting also increases beta-adrenergic responses of carbohydrate metabolism. These differential characteristics were studied further by comparing cyclic adenosine monophosphate (cAMP) accumulation and beta-adrenergic binding in normal and 3-day unweighted or denervated soleus muscle. Submaximal amounts of isoproterenol, a p-agonist, increased cAMP accumulation in vitro and in vivo (by intramuscular (IM) injection) to a greater degree (P less than .05) in unweighted muscles. Forskolin or maximal isoproterenol had similar in vitro effects in all muscles, suggesting increased beta-adrenergic sensitivity following unweighting. Increased sensitivity was confirmed by a greater receptor density (B(sub max)) for iodo-125(-)-pindolol in particulate preparations of unweighted (420 x 10(exp -18) mol/mg muscle) than of control or denervated muscles (285 x 10(exp-18) mol/mg muscle). The three dissociation constant (Kd) values were similar (20.3 to 25.8 pmol/L). Total binding capacity (11.4 fmol/muscle) did not change during 3 days of unweighting, but diminished by 30% with denervation. This result illustrates the "sparing" and loss of receptors, respectively, in these two atrophy models. In diabetic animals, IM injection of insulin diminished CAMP accumulation in the presence of theophylline in unweighted muscle (-66% +/- 2%) more than in controls (-42% +'- 6%, P less than .001). These results show that insulin affects CAMP formation in muscle, and support a greater in vivo insulin response following unweighting atrophy. These various data support a role for lysosomal proteolysis in denervation, but not in unweighting, atrophy.

Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis.

PubMed

Matsuzaki, K

2006-06-01

Transforming growth factor-beta (TGF-beta) signaling occurring during human colorectal carcinogenesis involves a shift in TGF-beta function, reducing the cytokine's antiproliferative effect, while increasing actions that promote invasion and metastasis. TGF-beta signaling involves phosphorylation of Smad3 at serine residues 208 and 213 in the linker region and serine residues 423 and 425 in the C-terminal region. Exogenous TGF-beta activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), changing unphosphorylated Smad3 to its phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker phosphorylated Smad3 (pSmad3L). Either pSmad3C or pSmad3L oligomerizes with Smad4, and translocates into nuclei. While the TbetaRI/pSmad3C pathway inhibits growth of normal epithelial cells in vivo, JNK/pSmad3L-mediated signaling promotes tumor cell invasion and extracellular matrix synthesis by activated mesenchymal cells. Furthermore, hepatocyte growth factor signaling interacts with TGF-beta to activate the JNK/pSmad3L pathway, accelerating nuclear transport of cytoplasmic pSmad3L. This reduces accessibility of unphosphorylated Smad3 to membrane-anchored TbetaRI, preventing Smad3C phosphorylation, pSmad3C-mediated transcription, and antiproliferative effects of TGF-beta on epithelial cells. As neoplasia progresses from normal colorectal epithelium through adenoma to invasive adenocarcinoma with distant metastasis, nuclear pSmad3L gradually increases while pSmad3C decreases. The shift from TbetaRI/pSmad3C-mediated to JNK/pSmad3L-mediated signaling is a major mechanism orchestrating a complex transition of TGF-beta signaling during sporadic human colorectal carcinogenesis. This review summarizes the recent understanding of Smad3 phosphoisoform-mediated signaling, particularly 'cross-talk' between Smad3 and JNK pathways that cooperatively promote oncogenic activities. Understanding of these actions should help to develop more effective therapy against human colorectal cancer, involving inhibition of JNK/pSmad3L pathway.

[Relation between the level of TPS, NSE, CEA and beta2-mG in the serum and the biological behavior of small cell lung cancer].

PubMed

Chen, Ming-sheng; Xu, Yan; Ma, Jing; Wu, Chang-gui; Hao, Xiao-ke; Lu, Bao-bi; Liu, Tian

2007-08-01

To study the relation between the level of tissue polypeptide specific antigen (TPS), neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and beta(2)-microglobulin (beta(2)-mG) in serum and the biological behavior of lung cancer for the more scientific diagnosis of lung cancer. To detect the level of TPS, NSE, CEA and beta(2)-mG in the serum of 94 patients with small cell lung cancer (SCLC), 86 patients with benign pulmonary diseases (BPD) and 89 patients in normal control group, the level of serum were examined by ELISA and immunoradiometric assay. The level of TPS and NSE in the serum of SCLC group [(437.8+/-516.6) U/L, (76.8+/-91.4) microg/L] were much higher than those in BPD group [(143.6+/-78.7) U/L, (13.3+/-10.8) microg/L] and normal group [(98.4+/-58.9) U/L, (10.1+/-5.7) microg/L, P<0.01)], and the level of CEA and beta(2)-mG in the serum of SCLC group were also obviously higher than those in normal group and BPD group (P<0.01). The sensitivity, specificity and accuracy of SCLC'S diagnosis by an indicator of TPS and NSE were 84.4%, 87.8%, 83.6% and 79.3%, 93.7%, 88.3%, respectively, and were much higher than CEA and beta(2)-Mg. In addition, the level of TPS and NSE in the patients' serum with metastatic SCLC were markedly higher than those in the patients with SCLC without metastasis, increased with the number of metastatic focuses. In clinical practice, the possibility of smokers suffering from lung cancer disease is 8 to 10 times higher than that of no-smokers, and 10 to 24 times higher of the people who smoked 30 to 40 cigarettes per day. From this comparison, the amount of smoking was closely related to the occurrence of lung cancer. TPS, NSE, CEA and beta(2)-mG in serum are useful for early diagnosis of lung cancer. There is complementarity in the combined detection of the level of TPS, NSE, CEA and beta(2)-MG. Their levels have close correlation with lung cancer, histological grades and lymphoid nodule metastasis.

Strong linkage disequilibrium of a HbE variant with the (AT)9(T)5 repeat in the BP1 binding site upstream of the beta-globin gene in the Thai population.

PubMed

Ohashi, Jun; Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Brittenham, Gary; Looareesuwan, Sornchai; Clark, Andrew G; Tokunaga, Katsushi

2005-01-01

A binding site for the repressor protein BP1, which contains a tandem (AT)x(T)y repeat, is located approximately 530 bp 5' to the human beta-globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)9(T)5 allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)x(T)y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; beta26Glu-->Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)9(T)5 and (AT)7(T)7 alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT)9(T)5 allele, which can explain why the betaE chain is inefficiently synthesized compared to the normal betaA chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT)9(T)5 repeat on the HbE chromosome. In addition, a novel (AC)n polymorphism adjacent to the (AT)x(T)y repeat (i.e., (AC)3(AT)7(T)5) was found through the variation screening in this study.

Pathogenic prions deviate PrPC signaling in neuronal cells and impair A-beta clearance

PubMed Central

Pradines, E; Hernandez-Rapp, J; Villa-Diaz, A; Dakowski, C; Ardila-Osorio, H; Haik, S; Schneider, B; Launay, J-M; Kellermann, O; Torres, J-M; Mouillet-Richard, S

2013-01-01

The subversion of the normal function exerted by the cellular prion protein (PrPC) in neurons by pathogenic prions is assumed to have a central role in the pathogenesis of transmissible spongiform encephalopathies. Using two murine models of prion infection, the 1C11 neuronal cell line and neurospheres, we document that prion infection is associated with the constitutive activation of signaling targets normally coupled with PrPC, including the Fyn kinase, the mitogen-associated protein kinases ERK1/2 and the CREB transcription factor. PrPC-dependent signaling overactivation in infected cells is associated with the recruitment of p38 and JNK stress-associated kinases. Downstream from CREB, prion-infected cells exhibit reduced activity of the matrix metalloprotease (MMP)-9. As MMP-9 catalyzes the degradation of the amyloid A-beta peptide, the decrease in MMP-9 activity in prion-infected cells causes a significant impairment of the clearance of A-beta, leading to its accumulation. By exploiting two 1C11-infected clones accumulating high or moderate levels of prions, we show that the prion-induced changes are correlated with the level of infectivity. Of note, a dose-dependent increase in A-beta levels was also found in the cerebrospinal fluid of mice inoculated with these infected clones. By demonstrating that pathogenic prions trigger increases in A-beta levels through the deviation of PrPC signaling, our data argue that A-beta may exacerbate prion-induced toxicity. PMID:23303130

Heterogeneity of cellular proliferation within transitional cell carcinoma: correlation of protein kinase C alpha/betaI expression and activity.

PubMed

Aaltonen, Vesa; Koivunen, Jussi; Laato, Matti; Peltonen, Juha

2006-07-01

A total of 18 histological samples containing both transitional cell carcinoma (TCC) and normal urothelial epithelium were analyzed for protein kinase C (PKC)-alpha and -betaI expression, and for their phosphorylated substrates. The results showed an increased expression of PKC-alpha in 13 out of 18 samples and -betaI in 11 out of 18 TCC samples when compared with normal urothelium. In addition, 11 out of 18 of the TCC tumors displayed heterogeneous expression of the PKC isoenzymes, with different levels of immunosignal in different areas of the tumor. Within the same sample, areas of highest PKC isoenzyme expression also showed highest classical PKC activity, as estimated by immunodetection of phosphorylated forms of PKC substrates. The areas of highest expression of PKC-alpha and/or -betaI isoenzymes showed also the highest number of cells positive for Ki67, an indicator of proliferation. Immunofluorescence and Western blotting demonstrated that in cultured TCC cells, PKC-alpha was located in the cytoplasm, whereas PKC-betaI was located primarily in the nucleus as a 65-kDa fragment and in the cytoplasm as a full-size 79-kDa protein. Our results indicate that increased expression of PKC-alpha and -betaI leads to increased total classical PKC kinase activity and suggest that increased activity of the isoenzymes plays a role in accelerated growth of TCC. Furthermore, these results suggest that even in carcinoma tissue, PKC expression and activity are under strict control.

The lifespan trajectory of neural oscillatory activity in the motor system.

PubMed

Heinrichs-Graham, Elizabeth; McDermott, Timothy J; Mills, Mackenzie S; Wiesman, Alex I; Wang, Yu-Ping; Stephen, Julia M; Calhoun, Vince D; Wilson, Tony W

2018-04-01

Numerous studies connect beta oscillations in the motor cortices to volitional movement, and beta is known to be aberrant in multiple movement disorders. However, the dynamic interplay between these beta oscillations, motor performance, and spontaneous beta power (e.g., during rest) in the motor cortices remains unknown. This study utilized magnetoencephalography (MEG) to investigate these three parameters and their lifespan trajectory in 57 healthy participants aged 9-75 years old. Movement-related beta activity was imaged using a beamforming approach, and voxel time series data were extracted from the peak voxels in the primary motor cortices. Our results indicated that spontaneous beta power during rest followed a quadratic lifespan trajectory, while movement-related beta oscillations linearly increased with age. Follow-on analyses showed that spontaneous beta power and the beta minima during movement, together, significantly predicted task performance above and beyond the effects of age. These data are the first to show lifespan trajectories among measures of beta activity in the motor cortices, and suggest that the healthy brain compensates for age-related increases in spontaneous beta activity by increasing the strength of beta oscillations within the motor cortices which, when successful, enables normal motor performance into later life. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Unraveling the contribution of pancreatic beta-cell suicide in autoimmune type 1 diabetes✩

PubMed Central

Jaberi-Douraki, Majid; Schnell, Santiago; Pietropaolo, Massimo; Khadra, Anmar

2014-01-01

In type 1 diabetes, an autoimmune disease mediated by autoreactive T-cells that attack insulin-secreting pancreatic beta-cells, it has been suggested that disease progression may additionally require protective mechanisms in the target tissue to impede such auto-destructive mechanisms. We hypothesize that the autoimmune attack against beta-cells causes endoplasmic reticulum stress by forcing the remaining beta-cells to synthesize and secrete defective insulin. To rescue beta-cell from the endoplasmic reticulum stress, beta-cells activate the unfolded protein response to restore protein homeostasis and normal insulin synthesis. Here we investigate the compensatory role of unfolded protein response by developing a multi-state model of type 1 diabetes that takes into account beta-cell destruction caused by pathogenic autoreactive T-cells and apoptosis triggered by endoplasmic reticulum stress. We discuss the mechanism of unfolded protein response activation and how it counters beta-cell extinction caused by an autoimmune attack and/or irreversible damage by endoplasmic reticulum stress. Our results reveal important insights about the balance between beta-cell destruction by autoimmune attack (beta-cell homicide) and beta-cell apoptosis by endoplasmic reticulum stress (beta-cell suicide). It also provides an explanation as to why the unfolded protein response may not be a successful therapeutic target to treat type 1 diabetes. PMID:24831415

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patrick, N.; Miyakawa, F.; Hunt, J.A.

The distribution of {beta}-thalassemia [{beta}{sup Th}] mutations is unique to each ethnic group. Most mutations affect one or a few bases; large deletions have been rare. Among families screened in Hawaii, [{beta}{sup Th}] heterozygotes were diagnosed by microcytosis, absence of abnormal hemoglobins on isoelectric focusing, and raised Hb A{sub 2} by chromatography. Gene frequency for {beta}{sup Th} was 0.02 in Filipinos. In Filipinos, polymerase chain reaction [PCR] with denaturing gradient gel electrophoresis for {beta}{sup Th} mutations detected a mutation in only 6 of 42 {beta}{sup Th} heterozygotes; an IVS2-666 C/T polymorphism showed non-heterozygosity in 37 and heterozygosity in only 5more » of these {beta}{sup Th} heterozygotes. One {beta}{sup Th}/{beta}{sup Th} major patient and his mother had no mutation detected by allele-specific oligomer hybridization; PCR failed to amplify any DNA from his {beta}-globin gene. After a total {beta}-globin gene deletion [{beta}{sup Del}] was found in a Filipino family in Ontario, specific PCR amplification for {beta}{sup Del} detected this in 43 of 53 {beta}{sup Th} Filipino samples tested; the above {beta}{sup Th}/{beta}{sup Th} patient was a ({beta}{sup Del}/{beta}{sup Del}) homozygote. The {beta}{sup Del} may account for over 60% of all {beta}{sup Th} alleles in Filipinos; this is the highest proportion of a deletion {beta}{sup Th} mutation reported from any population. Most but not all {beta}{sup Del} heterozygotes had high Hb F [5.13 {plus_minus} 3.94 mean {plus_minus} 1 s.d.] compared to the codon 41/42 four base deletion common in Chinese [2.30 {plus_minus} 0.86], or to {beta}{sup Th} heterozygotes with normal {alpha}-globin genes [2.23 {plus_minus} 0.80].« less

Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovary disease.

PubMed

Martínez-Guisasola, J; Guerrero, M; Alonso, F; Díaz, F; Cordero, J; Ferrer, J

2001-02-01

The aim of this study was to determine the influence of body weight on circulating plasma levels of beta-endorphin and insulin in women with polycystic ovary disease (PCOD), as well as the correlation between the plasma levels of beta-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with PCOD were recruited, 117 of whom had normal weight (body mass index (BMI) < 25) while 50 were obese (BMI > 25). A venous blood sample was taken and plasma concentrations of beta-endorphin, insulin, gonadotropins, prolactin, progesterone, 17 beta-estradiol, estrone, androgens, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) were measured. Mean beta-endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese PCOD women than in non-obese ones. Correlation analysis showed a positive association between insulin and beta-endorphin, beta-endorphin and BMI (and weight), insulin and BMI (and weight), and a negative correlation was found between insulin and SHBG. A weak association was found between beta-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma beta-endorphin concentrations correlate more with BMI than with insulinemia.

Impaired expression of importin/karyopherin {beta}1 leads to post-implantation lethality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miura, Katsutaka; Yoshinobu, Kumiko; Imaizumi, Takashi

2006-03-03

Importin {beta}1 (Imp{beta})/karyopherin {beta}1 (Kpnb1) mediates the nuclear import of a large variety of substrates. This study aimed to investigate the requirement for the Kpnb1 gene in mouse development, using a gene trap line, B6-CB-Ayu8108 {sup GtgeoIMEG} (Ayu8108 {sup geo}), in which the trap vector was inserted into the promoter region of the Kpnb1 gene, but in reverse orientation of the Kpnb1 gene. Ayu8108 {sup geo/geo} homozygous embryos could develop to the blastocyst stage, but died before embryonic day 5.5, and expression of the Kpnb1 gene in homozygous blastocysts was undetectable. We also replaced the {beta}geo gene with Imp{beta} cDNAmore » through Cre-mediated recombination to rescue Imp{beta} expression. Homozygous mice for the rescued allele Ayu8108 {sup Imp{beta}}{sup /Imp{beta}} were born and developed normally. These results demonstrated that the cause of post-implantation lethality of Ayu8108 {sup geo/geo} homozygous embryos was impaired expression of the Kpnb1 gene, indicating indispensable roles of Imp{beta}1 in early development of mice.« less

Cannabinoid receptor CB1 mRNA is highly expressed in the rat ciliary body: implications for the antiglaucoma properties of marihuana.

PubMed

Porcella, A; Casellas, P; Gessa, G L; Pani, L

1998-07-15

We used RT-PCR to measure relative differences in cannabinoid receptor (CB) mRNAs in the rat eye, comparing CB1 or CB2 transcripts to that of the normalizing reference gene beta2 microglobulin (beta2m). Significantly higher levels of CB1 mRNA levels were found in the ciliary body (0.84+/-0.05% of beta2m) than in the iris, (0.34+/-0.04% of beta2m), retina (0.07+/-0.005% of beta2m) and choroid (0.06+/-0.005% of beta2m). CB2 mRNA was undetectable. This expression pattern supports a specific role for the CB1 receptor in controlling intraocular pressure, helping to explain the antiglaucoma property of cannabinoids. Copyright 1998 Elsevier Science B.V. All rights reserved.

Structure-activity relationship studies of (+/-)-terbutaline and (+/-)-fenoterol on beta3-adrenoceptors in the guinea pig gastric fundus.

PubMed

Horinouchi, T; Nakagawa, Y; Wakabayashi, M; Koike, K

2001-08-01

(+/-)-Terbutaline and (+/-)-fenoterol are both arylethanolamine analogs that have tertbutyl and aryliso-propyl substituents respectively at the a position on the nitrogen of the ethanolamine side chain. In the present study, we have investigated the structure-activity relationships of (+/-)-terbutaline and (+/-)-fenoterol as beta3-adrenoceptor agonists in the guinea pig gastric fundus. (+/-)-Terbutaline and (+/-)-fenoterol induced concentration-dependent relaxation of the precontracted gastric fundus with pD2 values of 4.45+/-0.10 and 5.90+/-0.09, and intrinsic activities of 1.00+/-0.03 and 0.99+/-0.01 respectively. The combination of the selective beta1-adrenoceptor antagonist (+/-)-atenolol (100 microM), and the selective beta2-adrenoceptor antagonist (+/-)-butoxamine (100 microM), produced a 2 and 6 fold rightward shift of the concentration-response curves for (+/-)-terbutaline and (+/-)-fenoterol respectively, without depressing the maximal responses. The order of potency of these agonists was (pD2 value): (+/-)-fenoterol (5.09+/-0.10) > (+/-)-terbutaline (4.13+/-0.08). In the presence of (+/-)-atenolol and (+/-)-butoxamine, however, the non-selective beta1, beta2- and beta3-adrenoceptor antagonist (+/-)-bupranolol caused a concentration-dependent rightward shift of the concentration-response curves for (+/-)-terbutaline and (+/-)-fenoterol. Schild plot analyses of the effects of (+/-)-bupranolol against these agonists gave pA2 values of 6.21+/-0.07 ((+/-)-terbutaline) and 6.37+/-0.06 ((+/-)-fenoterol) respectively, and the slopes of the Schild plot were not significantly different from unity (p>0.05). These results suggest that the relaxant responses to (+/-)-terbutaline and (+/-)-fenoterol are mainly mediated through beta3-adrenoceptors in the guinea pig gastric fundus. The beta3-adrenoceptor agonist potencies of arylethanolamine analogs depend on the size of the end of the alkylamine side chain.

Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function.

PubMed

Takasu, Toshiyuki; Ukai, Masashi; Sato, Shuichi; Matsui, Tetsuo; Nagase, Itsuro; Maruyama, Tatsuya; Sasamata, Masao; Miyata, Keiji; Uchida, Hisashi; Yamaguchi, Osamu

2007-05-01

We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human beta3-adrenoceptor (AR). The half-maximal effective concentration (EC50) value was 22.4 nM. EC50 values of YM178 for human beta1- and beta2-ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective beta-AR agonist) was 0.8 for human beta3-ARs, 0.1 for human beta1-ARs, and 0.1 for human beta2-ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (beta3-AR agonist). EC50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10(-6) M CCh were 5.1 and 1.4 microM, respectively, whereas those in human bladder strips precontracted with 10(-7) M CCh were 0.78 and 0.28 microM, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence.

Activities and sources of beta-lactamase in sputum from patients with bronchiectasis.

PubMed Central

Dragicevic, P; Hill, S L; Burnett, D; Merrikin, D; Stockley, R A

1989-01-01

beta-Lactamase activity was measured in secretions from patients with bronchiectasis. Of 28 sputum samples, 23 contained measurable amounts of activity; values were significantly higher (P less than 0.01) in purulent samples than in mucoid or mucopurulent samples. beta-Lactamase activity was usually present in saliva collected before and between sputum expectorations, although values for sputum were higher than for either group of saliva samples (P less than 0.025 and P less than 0.005, respectively). This difference suggests that at least part of sputum beta-lactamase activity originates in the bronchial tree. Detailed microbiological study of a further eight specimens (seven were beta-lactamase positive) led to the isolation of Haemophilus influenzae from six, although only two of these isolates were beta-lactamase positive. Several other beta-lactamase-producing organisms were also isolated, including Staphylococcus aureus (n = 3), Escherichia coli (n = 1), Proteus spp. (n = 1), and Bacteroides spp. (n = 3). Size-exclusion high-performance liquid chromatography of the sputum showed several peaks of beta-lactamase activity which usually coeluted in fractions similar to those of their beta-lactamase-positive isolates. Therefore, sources of sputum beta-lactamases are often bacteria not considered truly pathogenic or not isolated during routine bacteriological assessment. These observations should be considered when embarking on antimicrobial therapy in bronchiectatic patients and suggest that increased dosages of penicillins are indicated. PMID:2663911

Preparation of powders suitable for conversion to useful .beta.-aluminas

DOEpatents

Morgan, Peter E. D.

1982-01-01

A process for forming a precursor powder which, when suitably pressed and sintered forms highly pure, densified .beta.- or .beta."-alumina, comprising the steps of: (1) forming a suspension (or slurry) of Bayer-derived Al(OH).sub.3 in a water-miscible solvent; (2) adding an aqueous solution of a Mg compound, a Li compound, a Na compound or mixtures thereof to the Bayer-derived Al(OH).sub.3 suspension while agitating the mixture formed thereby, to produce a gel; (3) drying the gel at a temperature above the normal boiling point of water to produce a powder material; (4) lightly ball milling and sieving said powder material; and (5) heating the ball-milled and sieved powder material at a temperature of between 350.degree. to 900.degree. C. to form the .beta.- or .beta."-alumina precursor powder. The precursor powder, thus formed, may be subsequently isopressed at a high pressure and sintered at an elevated temperature to produce .beta.- or .beta."-alumina. BACKGROUND OF THE INVENTION

Bioactive metabolites from the fungus Nectria galligena, the main apple canker agent in Chile.

PubMed

Gutiérrez, Margarita; Theoduloz, Cristina; Rodríguez, Jaime; Lolas, Mauricio; Schmeda-Hirschmann, Guillermo

2005-10-05

The phytopathogenic fungus Nectria galligena Bres. is the most common canker disease agent of hardwood trees. The terpenoids colletochlorin B, colletorin B, ilicicolin C, E, and F, as well as the phytotoxin alpha,beta-dehydrocurvularin have been isolated from liquid cultures of N. galligena obtained from the xylem of infected apple trees in central Chile. Ilicicolin C and F and alpha,beta-dehydrocurvularin were active against Pseudomonas syringae with IC50 values of 28.5, 28.5, and 14.2 microg/mL, respectively, in the same range as streptomycin and penicillin G (11 and 15 microg/mL, respectively). All of the compounds showed moderate inhibitory activity toward the enzymes acetylcholinesterase (AChE) and beta-glucuronidase. The most active enzyme inhibitors were colletochlorin B and ilicicolin C and E, with IC50 values of 30-36 microg/mL in the AChE assay and 32-43 microg/mL in the beta-glucuronidase test. All of the chlorinated compounds showed some toxicity toward human lung fibroblasts, with IC50 values in the range of 64-120 microg/mL. alpha,beta-Dehydrocurvularin proved to be the most toxic compound, showing IC50 values less than 12 microg/mL. The effect of the isolated compounds on seed germination and radicle and epicotyl growth was assessed in lettuce and millet seeds. At 100 and 200 microg/disk, alpha,beta-dehydrocurvularin significantly reduced radicle length and epicotyl growth in Lactuca sativa. This is the first report on the occurrence of colletochlorin B, colletorin B, ilicicolin C, E, and F, as well as alpha,beta-dehydrocurvularin associated to N. galligena.

High beta-N experiments at JET

NASA Astrophysics Data System (ADS)

Challis, Clive

2007-11-01

JET has investigated the performance potential and limitations of highly triangular plasmas relevant to fully non-inductive tokamak operation. The q-profile shape has been varied from cases with highly negative core magnetic shear to low shear with q0 close to 1, allowing the effect on confinement and stability to be studied. Operation with beta-N above the no-wall `limit' has been demonstrated for durations comparable with the resistive time and direct measurements of the no-wall beta have been developed as a tool for systematic performance optimization. Regimes have been developed with ITBs at reduced plasma current and toroidal field (1.2-1.5MA/2.3-2.7T) to obtain high values of beta-N and beta-P with either impurity seeding or quasi-double-null plasma configurations used to mitigate ELMs. The importance of the q-profile shape for performance optimization has been demonstrated in plasmas without ITBs (1.2MA/1.8T) with low values of minimum q (1-2) providing access to the highest beta-N (above 3).

Length dependence of electron transport through molecular wires--a first principles perspective.

PubMed

Khoo, Khoong Hong; Chen, Yifeng; Li, Suchun; Quek, Su Ying

2015-01-07

One-dimensional wires constitute a fundamental building block in nanoscale electronics. However, truly one-dimensional metallic wires do not exist due to Peierls distortion. Molecular wires come close to being stable one-dimensional wires, but are typically semiconductors, with charge transport occurring via tunneling or thermally-activated hopping. In this review, we discuss electron transport through molecular wires, from a theoretical, quantum mechanical perspective based on first principles. We focus specifically on the off-resonant tunneling regime, applicable to shorter molecular wires (<∼4-5 nm) where quantum mechanics dictates electron transport. Here, conductance decays exponentially with the wire length, with an exponential decay constant, beta, that is independent of temperature. Different levels of first principles theory are discussed, starting with the computational workhorse - density functional theory (DFT), and moving on to many-electron GW methods as well as GW-inspired DFT + Sigma calculations. These different levels of theory are applied in two major computational frameworks - complex band structure (CBS) calculations to estimate the tunneling decay constant, beta, and Landauer-Buttiker transport calculations that consider explicitly the effects of contact geometry, and compute the transmission spectra directly. In general, for the same level of theory, the Landauer-Buttiker calculations give more quantitative values of beta than the CBS calculations. However, the CBS calculations have a long history and are particularly useful for quick estimates of beta. Comparing different levels of theory, it is clear that GW and DFT + Sigma calculations give significantly improved agreement with experiment compared to DFT, especially for the conductance values. Quantitative agreement can also be obtained for the Seebeck coefficient - another independent probe of electron transport. This excellent agreement provides confirmative evidence of off-resonant tunneling in the systems under investigation. Calculations show that the tunneling decay constant beta is a robust quantity that does not depend on details of the contact geometry, provided that the same contact geometry is used for all molecular lengths considered. However, because conductance is sensitive to contact geometry, values of beta obtained by considering conductance values where the contact geometry is changing with the molecular junction length can be quite different. Experimentally measured values of beta in general compare well with beta obtained using DFT + Sigma and GW transport calculations, while discrepancies can be attributed to changes in the experimental contact geometries with molecular length. This review also summarizes experimental and theoretical efforts towards finding perfect molecular wires with high conductance and small beta values.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorodetsky, R.; Goldfarb, A.; Dagan, I.

Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for noninvasive determination of iron and zinc in two distinct skin areas, representing predominantly dermal and epidermal tissues, in 56 patients with beta-thalassemia major and intermedia. The mean iron levels in the skin of patients with beta-thalassemia major and intermedia were elevated by greater than 200% and greater than 50%, respectively, compared with control values. The zinc levels of both skin areas examined were within the normal range. The data indicate that the rate and number of blood transfusions, which correlated well with serum ferritin levels (r .more » 0.8), are not the only factors that determine the amount of iron deposition in the skin (r less than 0.6). Other sources of iron intake contribute to the total iron load in the tissues, particularly in patients who are not given multiple transfusions. The noninvasive quantitation of skin levels may reflect the extent of iron deposition in major parenchymal organs. Repeated DXS examinations of the skin could monitor the clearance of iron from the tissues of patients with iron overload in the course of therapy with chelating agents.« less

Statistical analysis of m/ n = 2/1 locked and quasi-stationary modes with rotating precursors at DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sweeney, Ryan Myles; Choi, W.; La Haye, R. J.

A database has been developed to study the evolution, the nonlinear effects on equilibria, and the disruptivity of locked and quasi-stationary modes with poloidal and toroidal mode numbers m = 2 and n = 1 at DIII-D. The analysis of 22500 discharges shows that more than 18% of disruptions are due to locked or quasi-stationary modes with rotating precursors (not including born locked modes). A parameter formulated by the plasma internal inductance l i divided by the safety factor at 95% of the poloidal flux, q 95, is found to exhibit predictive capability over whether a locked mode will cause a disruption or not, and does so up to hundreds of milliseconds before the disruption. Within 20 ms of the disruption, the shortest distance between the island separatrix and the unperturbed last closed flux surface, referred to as d edge, performs comparably tomore » $${{l}_{i}}/{{q}_{95}}$$ in its ability to discriminate disruptive locked modes. Out of all parameters considered, d edge also correlates best with the duration of the locked mode. Disruptivity following a m/n = 2/1 locked mode as a function of the normalized beta, $${{\\beta}_{\\text{N}}}$$ , is observed to peak at an intermediate value, and decrease for high values. The decrease is attributed to the correlation between $${{\\beta}_{\\text{N}}}$$ and q 95 in the DIII-D operational space. Within 50 ms of a locked mode disruption, average behavior includes exponential growth of the n = 1 perturbed field, which might be due to the 2/1 locked mode. Surprisingly, even assuming the aforementioned 2/1 growth, disruptivity following a locked mode shows little dependence on island width up to 20 ms before the disruption. Separately, greater deceleration of the rotating precursor is observed when the wall torque is large. At locking, modes are often observed to align at a particular phase, which is likely related to a residual error field. Timescales associated with the mode evolution are also studied and dictate the response times necessary for disruption avoidance and mitigation. Lastly, observations of the evolution of $${{\\beta}_{\\text{N}}}$$ during a locked mode, the effects of poloidal beta on the saturated width, and the reduction in Shafranov shift during locking are also presented.« less

Statistical analysis of m/ n = 2/1 locked and quasi-stationary modes with rotating precursors at DIII-D

DOE PAGES

Sweeney, Ryan Myles; Choi, W.; La Haye, R. J.; ...

2016-11-01

A database has been developed to study the evolution, the nonlinear effects on equilibria, and the disruptivity of locked and quasi-stationary modes with poloidal and toroidal mode numbers m = 2 and n = 1 at DIII-D. The analysis of 22500 discharges shows that more than 18% of disruptions are due to locked or quasi-stationary modes with rotating precursors (not including born locked modes). A parameter formulated by the plasma internal inductance l i divided by the safety factor at 95% of the poloidal flux, q 95, is found to exhibit predictive capability over whether a locked mode will cause a disruption or not, and does so up to hundreds of milliseconds before the disruption. Within 20 ms of the disruption, the shortest distance between the island separatrix and the unperturbed last closed flux surface, referred to as d edge, performs comparably tomore » $${{l}_{i}}/{{q}_{95}}$$ in its ability to discriminate disruptive locked modes. Out of all parameters considered, d edge also correlates best with the duration of the locked mode. Disruptivity following a m/n = 2/1 locked mode as a function of the normalized beta, $${{\\beta}_{\\text{N}}}$$ , is observed to peak at an intermediate value, and decrease for high values. The decrease is attributed to the correlation between $${{\\beta}_{\\text{N}}}$$ and q 95 in the DIII-D operational space. Within 50 ms of a locked mode disruption, average behavior includes exponential growth of the n = 1 perturbed field, which might be due to the 2/1 locked mode. Surprisingly, even assuming the aforementioned 2/1 growth, disruptivity following a locked mode shows little dependence on island width up to 20 ms before the disruption. Separately, greater deceleration of the rotating precursor is observed when the wall torque is large. At locking, modes are often observed to align at a particular phase, which is likely related to a residual error field. Timescales associated with the mode evolution are also studied and dictate the response times necessary for disruption avoidance and mitigation. Lastly, observations of the evolution of $${{\\beta}_{\\text{N}}}$$ during a locked mode, the effects of poloidal beta on the saturated width, and the reduction in Shafranov shift during locking are also presented.« less

Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence

PubMed Central

Fernandez-Mendoza, Julio; Li, Yun; Vgontzas, Alexandros N.; Fang, Jidong; Gaines, Jordan; Calhoun, Susan L.; Liao, Duanping; Bixler, Edward O.

2016-01-01

Study Objectives: To examine whether insomnia is associated with spectral electroencephalographic (EEG) dynamics in the beta (15–35Hz) range during sleep in an adolescent general population sample. Methods: A case-control sample of 44 adolescents from the Penn State Child Cohort underwent a 9-h polysomnography, clinical history and physical examination. We examined low-beta (15–25 Hz) and high-beta (25–35 Hz) relative power at central EEG derivations during sleep onset latency (SOL), sleep onset (SO), non-rapid eye movement (NREM) sleep, and wake after sleep onset (WASO). Results: Compared to controls (n = 21), individuals with insomnia (n = 23) showed increased SOL and WASO and decreased sleep duration and efficiency, while no differences in sleep architecture were found. Insomniacs showed increased low-beta and high-beta relative power during SOL, SO, and NREM sleep as compared to controls. High-beta relative power was greater during all sleep and wake states in insomniacs with short sleep duration as compared to individuals with insomnia with normal sleep duration. Conclusions: Adolescent insomnia is associated with increased beta EEG power during sleep, which suggests that cortical hyperarousal is present in individuals with insomnia as early as adolescence. Interestingly, cortical hyperarousal is greatest in individuals with insomnia with short sleep duration and may explain the sleep complaints of those with normal sleep duration. Disturbed cortical networks may be a shared mechanism putting individuals with insomnia at risk of psychiatric disorders. Citation: Fernandez-Mendoza J, Li Y, Vgontzas AN, Fang J, Gaines J, Calhoun SL, Liao D, Bixler EO. Insomnia is associated with cortical hyperarousal as early as adolescence. SLEEP 2016;39(5):1029–1036. PMID:26951400

EEG activation differences in the pre-motor cortex and supplementary motor area between normal individuals with high and low traits of autism.

PubMed

Puzzo, Ignazio; Cooper, Nicholas R; Vetter, Petra; Russo, Riccardo

2010-06-25

The human mirror neuron system (hMNS) is believed to provide a basic mechanism for social cognition. Event-related desynchronization (ERD) in alpha (8-12Hz) and low beta band (12-20Hz) over sensori-motor cortex has been suggested to index mirror neurons' activity. We tested whether autistic traits revealed by high and low scores on the Autistic Quotient (AQ) in the normal population are linked to variations in the electroencephalogram (EEG) over motor, pre-motor cortex and supplementary motor area (SMA) during action observation. Results revealed that in the low AQ group, the pre-motor cortex and SMA were more active during hand action than static hand observation whereas in the high AQ group the same areas were active both during static and hand action observation. In fact participants with high traits of autism showed greater low beta ERD while observing the static hand than those with low traits and this low beta ERD was not significantly different when they watched hand actions. Over primary motor cortex, the classical alpha and low beta ERD during hand actions relative to static hand observation was found across all participants. These findings suggest that the observation-execution matching system works differently according to the degree of autism traits in the normal population and that this is differentiated in terms of the EEG according to scalp site and bandwidth. Copyright 2010 Elsevier B.V. All rights reserved.

Restitution of defective glucose-stimulated insulin secretion in diabetic GK rat by acetylcholine uncovers paradoxical stimulatory effect of beta-cell muscarinic receptor activation on cAMP production.

PubMed

Dolz, Manuel; Bailbé, Danielle; Giroix, Marie-Hélène; Calderari, Sophie; Gangnerau, Marie-Noelle; Serradas, Patricia; Rickenbach, Katharina; Irminger, Jean-Claude; Portha, Bernard

2005-11-01

Because acetylcholine (ACh) is a recognized potentiator of glucose-stimulated insulin release in the normal beta-cell, we have studied ACh's effect on islets of the Goto-Kakizaki (GK) rat, a spontaneous model of type 2 diabetes. We first verified that ACh was able to restore the insulin secretory glucose competence of the GK beta-cell. Then, we demonstrated that in GK islets 1) ACh elicited a first-phase insulin release at low glucose, whereas it had no effect in Wistar; 2) total phospholipase C activity, ACh-induced inositol phosphate production, and intracellular free calcium concentration ([Ca2+]i) elevation were normal; 3) ACh triggered insulin release, even in the presence of thapsigargin, which induced a reduction of the ACh-induced [Ca2+]i response (suggesting that ACh produces amplification signals that augment the efficacy of elevated [Ca2+]i on GK exocytosis); 4) inhibition of protein kinase C did not affect [Ca2+]i nor the insulin release responses to ACh; and 5) inhibition of cAMP-dependent protein kinases (PKAs), adenylyl cyclases, or cAMP generation, while not affecting the [Ca2+]i response, significantly lowered the insulinotropic response to ACh (at low and high glucose). In conclusion, ACh acts mainly through activation of the cAMP/PKA pathway to potently enhance Ca2+-stimulated insulin release in the GK beta-cell and, in doing so, normalizes its defective glucose responsiveness.

[Effects of jingui shenqi pill combined prednisone on expression of glucocorticoid receptor and its clinical effect in treating bullous pemphigoid patients].

PubMed

Liu, Bao-guo; Li, Zhi-ying; Du, Ming

2006-10-01

To investigate the effect of Jingui Shenqi Pill (JSP) on the expression of glucocorticoid receptor (GR) in the skin lesion and its clinical effect in treating bullous pemphigoid (BP) patients. Thirty BP patients were randomly divided into the treatment group (n=15) treated with JSP plus prednisone and the prednisone group (n=15) with prednisone alone both for 4 weeks. And a normal control group was set up also. Expressions of GR-alpha and GR-beta in the skin lesion of BP patients and the normal skin of the normal control were detected by immunohistochemical assay. Results The total effective rate was 93.33% in the treatment group, significantly higher than that in the prednisone group which was 73.33% (P < 0.05); GR-alpha expression was higher in the treatment group than that in other two groups (P < 0.01), while GR-beta expression in the treatment group was lower than that in the prednisone group (P < 0.01). JSP could increase GR-alpha expression and decrease GR-beta expression in the skin lesion of BP patients, so as to improve sensitivity of skin to glucocorticoid.

Evidence against involvement of the acid lysosomal sphingomyelinase in the tumor-necrosis-factor- and interleukin-1-induced sphingomyelin cycle and cell proliferation in human fibroblasts.

PubMed Central

Andrieu, N; Salvayre, R; Levade, T

1994-01-01

The hydrolysis of sphingomyelin (SPM) has been reported to mediate a number of responses to extracellular agents, including cytokines. The so-called SPM cycle may result from the activation of different types of sphingomyelinases (SPMases). We investigated the hypothetical contribution of acid lysosomal SPMase in the SPM signal-transduction pathway. We examined the ability of human skin fibroblasts with a genetic deficiency of acid lysosomal SPMase activity to respond to tumour necrosis factor alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). We report that both cytokines promoted SPM hydrolysis in fibroblasts derived from patients with Niemann-Pick disease or I-cell disease, similar to that observed in normal cells. Treatment of normal fibroblasts with cationic amphiphilic drugs resulted in inhibition of acid SPMase activity, but had no effect on cytokine-induced SPM turnover. In addition, TNF-alpha and IL-1 beta stimulated [3H]thymidine incorporation in Niemann-Pick fibroblasts, as in normal cells. Thus our results argue against a role for acid endolysosomal SPMase in mediating the cytokine-induced SPM signalling cascade. Images Figure 2 PMID:7980390

Hb Alesha [beta67(E11)Val-->Met, GTG-->ATG] in an Argentinean girl.

PubMed

Eberle, Silvia Eandi; Noguera, Nélida I; Sciuccati, Gabriela; Bonduel, Mariana; Díaz, Lilian; Staciuk, Raquel; Targovnik, Héctor M; Feliu-Torres, Aurora

2007-01-01

Hb Alesha is caused by a GTG-->ATG mutation at codon 67 of the beta-globin gene, resulting in abnormal beta-globin chains in which the normal beta67(E11) valine is changed to methionine. This hemoglobin (Hb) is also known as Hb Bristol, the first unstable Hb described, since in a fraction of the variant the methionine is modified into an aspartic acid by a posttranslational modification. This replacement disrupts the apolar bonds between the valine and the heme group, producing an unstable Hb and severe hemolysis. We have identified this rare hemoglobinopathy in an Argentinean girl with severe hemolytic anemia, splenomegaly and frequent requirement for red blood cell transfusions.

Hypothyroidism in utero stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation.

PubMed

Harris, Shelley E; De Blasio, Miles J; Davis, Melissa A; Kelly, Amy C; Davenport, Hailey M; Wooding, F B Peter; Blache, Dominique; Meredith, David; Anderson, Miranda; Fowden, Abigail L; Limesand, Sean W; Forhead, Alison J

2017-06-01

Thyroid hormones are important regulators of growth and maturation before birth, although the extent to which their actions are mediated by insulin and the development of pancreatic beta cell mass is unknown. Hypothyroidism in fetal sheep induced by removal of the thyroid gland caused asymmetric organ growth, increased pancreatic beta cell mass and proliferation, and was associated with increased circulating concentrations of insulin and leptin. In isolated fetal sheep islets studied in vitro, thyroid hormones inhibited beta cell proliferation in a dose-dependent manner, while high concentrations of insulin and leptin stimulated proliferation. The developing pancreatic beta cell is therefore sensitive to thyroid hormone, insulin and leptin before birth, with possible consequences for pancreatic function in fetal and later life. The findings of this study highlight the importance of thyroid hormones during pregnancy for normal development of the fetal pancreas. Development of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long-term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration in utero. Organ growth and pancreatic islet cell proliferation and mass were examined in sheep fetuses following removal of the thyroid gland in utero. The effects of triiodothyronine (T 3 ), insulin and leptin on beta cell proliferation rates were determined in isolated fetal ovine pancreatic islets in vitro. Hypothyroidism in the sheep fetus resulted in an asymmetric pattern of organ growth, pancreatic beta cell hyperplasia, and elevated plasma insulin and leptin concentrations. In pancreatic islets isolated from intact fetal sheep, beta cell proliferation in vitro was reduced by T 3 in a dose-dependent manner and increased by insulin at high concentrations only. Leptin induced a bimodal response whereby beta cell proliferation was suppressed at the lowest, and increased at the highest, concentrations. Therefore, proliferation of beta cells isolated from the ovine fetal pancreas is sensitive to physiological concentrations of T 3 , insulin and leptin. Alterations in these hormones may be responsible for the increased beta cell proliferation and mass observed in the hypothyroid sheep fetus and may have consequences for pancreatic function in later life. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Reduced expression of TGF beta is associated with advanced disease in transitional cell carcinoma.

PubMed Central

Coombs, L. M.; Pigott, D. A.; Eydmann, M. E.; Proctor, A. J.; Knowles, M. A.

1993-01-01

The gene structure and expression of the related peptide regulatory factors TGF beta 1 and TGF beta 2 were studied in a panel of seven urothelial carcinoma cell lines and 40 transitional cell carcinomas. The latter comprised 15 grade 1, 18 grade 2 and 5 grade 3 tumours and two cases of carcinoma in situ. Control tissues included ten matched 'field' biopsies and 17 other biopsies including 11 biopsies of macroscopically normal urothelium, two of which were from patients with no history of bladder cancer. No amplification of rearrangements of either TGF beta 1 or TGF beta 2 were detected in any sample. A complex pattern of expression or the two genes was found in the urothelial cell lines. High, but variable levels of the 2.5 kb TGF beta 1 transcript were detected and lower and more variable levels of the three (4.1 kb, 5.1 kb and 6.5 kb) transcripts of TGF beta 2 were detected. Although those cell lines expressing most TGF beta 1 tended to express less TGF beta 2 transcript there was no clear-cut relationship. In comparison, no TGF beta 2 transcript was identified in any primary transitional cell carcinoma or control tissue. Markedly reduced or undetectable levels of TGF beta 1 transcript were detected in 4/15 (26%) grade 1, 5/18 (28%) grade 2 and 3/5 (60%) grade 3 tumours. There was no clear relationship to tumour stage, lymphocytic infiltration or stromal content of the tumours. Clinical review one year after the 2 year period of tumour collection showed that 6/9 (66%) of patients with tumours with reduced levels of transcript had died or had disease which was not controllable by local resection and 3/9 (33%) had developed tumour re-occurrences. In comparison, in the group with normal levels of expression of TGF beta 1, 3/18 (17%) had disease which was not controllable by local means, 9/18 (50%) had tumour re-occurrence and 6/18 (33%) had no evidence of disease. The association of reduced expression of TGF beta 1 and advanced disease was statistically significant P < 0.02 (Fisher's test). Although the sample size is small, we suggest that the loss of expression of TGF beta 1 may be a potential marker of progressive disease or prognosis in transitional cell carcinoma and warrants further study. Images Figure 1 Figure 2 Figure 3 PMID:8439507

Evaluation of the time-concentration-mortality responses of Plutella xylostella larvae to the interaction of Isaria fumosorosea with the insecticides beta-cypermethrin and Bacillus thuringiensis.

PubMed

Nian, Xiao-ge; He, Yu-rong; Lu, Li-hua; Zhao, Rui

2015-02-01

Entomopathogenic fungi are potential candidates for controlling Plutella xylostella, a cosmopolitan pest of crucifers. In this study, bioassays were conducted to evaluate the interaction between Isaria fumosorosea and sublethal doses of two insecticides, beta-cypermethrin and Bacillus thuringiensis, against P. xylostella. Data of each assay were in good agreement with the time-concentration-mortality model, indicating a strong dependence of the fungus and insecticide interaction on both concentration and post-exposure time. Using beta-cypermethrin 58-116 µg mL(-1) or B. thuringiensis 222.5-890 µg mL(-1) with the fungus significantly enhanced fungal efficacy. The LC50 values of the fungus declined over a 1-7 day period after exposure, and the LT50 values decreased with increasing concentration. Based on LC50 or LC90 estimates, synergism between the fungus and beta-cypermethrin resulted in a 2.7-28.3-fold reduction in LC50 values and a 12.1-19.6-fold reduction in LC90 values, while synergism of the fungus with B. thuringiensis led to a 2.4-385.0-fold reduction in LC50 values and a 4.4-151.7-fold reduction in LC90 values. Results show that sublethal doses of B. thuringiensis and beta-cypermethrin can synergise I. fumosorosea activity on P. xylostella, suggesting that combination of I. fumosorosea with the two insecticides might offer an integrated approach to controlling P. xylostella in practice. © 2014 Society of Chemical Industry. © 2014 Society of Chemical Industry.

The region of formation of the ultraviolet high temperature resonance lines in the eclipsing binary Beta Persei (Algol)

NASA Technical Reports Server (NTRS)

Brandi, E.; Garcia, L. G.; Kondo, Y.; Sahade, J.

1989-01-01

A new series of IUE observations of Beta Persei has shown that the high temperature resonance lines of Si IV and C IV arise in a region that surrounds the brighter, early-type component of the system. The continuum spectrum corresponds to that of a B8V object, and the value of E(B-V) that yielded the best match between the two IUE regions was 0.06, the value quoted for Beta Per in Jamar et al.'s (1976) Catalog.

Characterization and inhibition of beta-adrenergic receptor kinase in intact myocytes.

PubMed

Laugwitz, K L; Kronsbein, K; Schmitt, M; Hoffmann, K; Seyfarth, M; Schömig, A; Ungerer, M

1997-08-01

beta-Adrenergic receptor kinase (beta ARK) phosphorylates and thereby inactivates agonist-occupied beta-adrenergic receptors (beta AR). beta ARK is thought to play an important role in the regulation of cardiac function. Therefore, we studied beta ARK activation and its inhibition in intact smooth muscle cells and in cardiomyoblasts. beta AR agonist-stimulated translocation of beta ARK was monitored by immunofluorescence labelling with specific antibodies and confocal laser scanning microscopy in DDT-MF 2 hamster smooth muscle cells and in H9c2 rat cardiomyoblasts. In unstimulated cells. beta ARK was mainly located in the cytosol. After beta AR agonist stimulation, the beta ARK signal was partially translocated to the membranes. Liposomal gene transfer of the COOH-terminus of beta ARK ('beta ARKmini') as a beta ARK inhibitor led to functional expression of this protein in both cell lines with high efficiency. Western blots with beta ARK antibodies showed a gene concentration-dependent immunoreactivity of the 'beta ARKmini' protein. 'beta ARKmini'-transfected myocytes demonstrated reduced membrane targeting of the beta ARK immuno-fluorescence signal. Additionally, the effect of 'beta ARKmini' on beta AR-induced desensitization of myocytic cAMP accumulation was investigated. In control cells, desensitization with isoproterenol led to a subsequent reduction of beta AR-induced cAMP accumulation. In 'beta ARKmini'-transfected myocytes, this beta AR-induced desensitization was significantly diminished, whereas normal beta AR-induced cAMP accumulation was unaffected. A gene concentration of 2 micrograms 'beta ARKmini' DNA/100,000 cardiomyoblasts, and of 0.7 microgram 'beta ARKmini' DNA/100,000 DDT-MF2 smooth muscle cells led to approximately 5.9- and approximately 5.6-fold overexpressions of 'beta ARKmini' vs. native beta ARK, respectively. These gene doses proved sufficient to attenuate beta-adrenergic desensitization significantly. (1) beta ARK translocation was evidenced in DDT-MF2 smooth muscle cells and in cardiomyoblasts by confocal laser scanning microscopy. (2) Feasibility of 'beta ARKmini' gene transfer to myocytes was demonstrated, and necessary gene doses for beta ARK inhibition were titered. (3) Overexpression of 'beta ARKmini' functionally interacted with endogenous beta-adrenergic signal transduction, leading to sustained cAMP accumulation after prolonged beta-adrenergic stimulation.

The role of outer membrane in Serratia marcescens intrinsic resistance to antibiotics.

PubMed

Sánchez, L; Ruiz, N; Leranoz, S; Viñas, M; Puig, M

1997-09-01

Three different porins from Serratia marcescens were described. They were named Omp1, Omp2 and Omp3 and their molecular weights were 42, 40 and 39 kDa respectively. Omp2 and Omp3 showed osmoregulation and thermoregulation in a similar way to OmpC and OmpF of Escherichia coli. Permeability coefficients of the outer membrane of this species were calculated following the Zimmermann and Rosselet method. P values were similar to those obtained in Escherichia coli, which suggests that the chromosomal beta-lactamase would play a major role in the resistance of Serratia marcescens to beta-lactam antibiotics. Both MIC values and permeabilities were modified by salycilates and acetylsalycilate. Synergism between the outer membrane and the beta-lactamase was also evaluated. When bacteria grew in the presence of a beta-lactam in the medium, the beta-lactamase accounted for most of the resistance.

Cytotoxicity of cardenolides and cardenolide glycosides from Asclepias curassavica.

PubMed

Li, Jun-Zhu; Qing, Chen; Chen, Chang-Xiang; Hao, Xiao-Jiang; Liu, Hai-Yang

2009-04-01

A new cardenolide, 12beta,14beta-dihydroxy-3beta,19-epoxy-3alpha-methoxy-5alpha-card-20(22)-enolide (6), and a new doubly linked cardenolide glycoside, 12beta-hydroxycalotropin (13), together with eleven known compounds, coroglaucigenin (1), 12beta-hydroxycoroglaucigenin (2), calotropagenin (3), desglucouzarin (4), 6'-O-feruloyl-desglucouzarin (5), calotropin (7), uscharidin (8), asclepin (9), 16alpha-hydroxyasclepin (10), 16alpha-acetoxycalotropin (11), and 16alpha-acetoxyasclepin (12), were isolated from the aerial part of ornamental milkweed, Asclepias curassavica and chemically elucidated through spectral analyses. All the isolates were evaluated for their cytotoxic activity against HepG2 and Raji cell lines. The results showed that asclepin (9) had the strongest cytotoxic activity with an IC(50) value of 0.02 microM against the two cancer cell lines and the new compound 13 had significant cytotoxic activity with IC(50) values of 0.69 and 1.46 microM, respectively.

Influence of Ginkgo Biloba extract (EGb 761) on expression of IL-1 Beta, IL-6, TNF-alfa, HSP-70, HSF-1 and COX-2 after noise exposure in the rat cochlea.

PubMed

Dogan, Remzi; Sjostrand, Alev Pektas; Yenıgun, Alper; Karatas, Ersin; Kocyigit, Abdurrahim; Ozturan, Orhan

2018-08-01

The objective of this study was to investigate the influence of Ginkgo Biloba in early treatment of noise induced hearing loss on expression of IL-6, IL-1 Beta, TNF-alfa, HSP-70, HSF-1 and COX-2 in the rat cochlea. Thirty two female rats were randomly divided into four groups (Acoustic Trauma, Ginkgo Biloba, Acoustic Trauma+Ginkgo Biloba, Non Treatment). Auditory brainstem response (ABR) was applied in all the groups. At the end of the study, IL-1Beta, IL-6, TNF-alpha, HSP-70, HSF-1 and COX-2 were studied in cochlear tissue with ELISA and Western blot analysis. There were significant increases in ABR values measured at days 1 and 7 compared to baseline values in Group 3. IL-1 Beta, IL-6 and TNF-alpha values were significantly higher in Group 1 than in the other groups. Whereas HSP-70 and HSF-1 values were found to be significantly lower in Group 1 compared to those in Group 2 and Group 3. COX-2 of Group 1 was significantly higher than the other groups. Ginkgo Biloba is helpful in the treatment of noise induced hearing loss and exerts its effect by inhibiting expression of IL-1 Beta, IL-6, TNF-alpha and COX-2 and increasing HSP-70 and HSF-1 values in rat cochlea. Copyright © 2017 Elsevier B.V. All rights reserved.

Defining a Role for the Oncogene Beta-Catenin in Prostate Epithelial Growth and Invasion

DTIC Science & Technology

2011-07-01

receptor function. To determine in increased or decreased Wnt signaling can affect androgen receptor function, we harvested E15.5 UGSs from Esr1 -Cre x...beta-cateninfl/fl and Esr1 -Cre APCfl/fl embryos and treated them with 2 uM tamoxifen and zero, low, normal, or high androgen to determine if high

Cloning, expression in Pichia pastoris, and characterization of a thermostable GH5 mannan endo-1,4-beta-mannosidase from Aspergillus niger BK01.

PubMed

Do, Bien-Cuong; Dang, Thi-Thu; Berrin, Jean-Guy; Haltrich, Dietmar; To, Kim-Anh; Sigoillot, Jean-Claude; Yamabhai, Montarop

2009-11-13

Mannans are key components of lignocellulose present in the hemicellulosic fraction of plant primary cell walls. Mannan endo-1,4-beta-mannosidases (1,4-beta-D-mannanases) catalyze the random hydrolysis of beta-1,4-mannosidic linkages in the main chain of beta-mannans. Biodegradation of beta-mannans by the action of thermostable mannan endo-1,4-beta-mannosidase offers significant technical advantages in biotechnological industrial applications, i.e. delignification of kraft pulps or the pretreatment of lignocellulosic biomass rich in mannan for the production of second generation biofuels, as well as for applications in oil and gas well stimulation, extraction of vegetable oils and coffee beans, and the production of value-added products such as prebiotic manno-oligosaccharides (MOS). A gene encoding mannan endo-1,4-beta-mannosidase or 1,4-beta-D-mannan mannanohydrolase (E.C. 3.2.1.78), commonly termed beta-mannanase, from Aspergillus niger BK01, which belongs to glycosyl hydrolase family 5 (GH5), was cloned and successfully expressed heterologously (up to 243 microg of active recombinant protein per mL) in Pichia pastoris. The enzyme was secreted by P. pastoris and could be collected from the culture supernatant. The purified enzyme appeared glycosylated as a single band on SDS-PAGE with a molecular mass of approximately 53 kDa. The recombinant beta-mannanase is highly thermostable with a half-life time of approximately 56 h at 70 degrees C and pH 4.0. The optimal temperature (10-min assay) and pH value for activity are 80 degrees C and pH 4.5, respectively. The enzyme is not only active towards structurally different mannans but also exhibits low activity towards birchwood xylan. Apparent Km values of the enzyme for konjac glucomannan (low viscosity), locust bean gum galactomannan, carob galactomannan (low viscosity), and 1,4-beta-D-mannan (from carob) are 0.6 mg mL-1, 2.0 mg mL-1, 2.2 mg mL-1 and 1.5 mg mL-1, respectively, while the kcat values for these substrates are 215 s-1, 330 s-1, 292 s-1 and 148 s-1, respectively. Judged from the specificity constants kcat/Km, glucomannan is the preferred substrate of the A. niger beta -mannanase. Analysis by thin layer chromatography showed that the main product from enzymatic hydrolysis of locust bean gum is mannobiose, with only low amounts of mannotriose and higher manno-oligosaccharides formed. This study is the first report on the cloning and expression of a thermostable mannan endo-1,4-beta-mannosidase from A. niger in Pichia pastoris. The efficient expression and ease of purification will significantly decrease the production costs of this enzyme. Taking advantage of its acidic pH optimum and high thermostability, this recombinant beta-mannanase will be valuable in various biotechnological applications.

Masses of {sup 130}Te and {sup 130}Xe and Double-{beta}-Decay Q Value of {sup 130}Te

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redshaw, Matthew; Mount, Brianna J.; Myers, Edmund G.

The atomic masses of {sup 130}Te and {sup 130}Xe have been obtained by measuring cyclotron frequency ratios of pairs of triply charged ions simultaneously trapped in a Penning trap. The results, with 1 standard deviation uncertainty, are M({sup 130}Te)=129.906 222 744(16) u and M({sup 130}Xe)=129.903 509 351(15) u. From the mass difference the double-{beta}-decay Q value of {sup 130}Te is determined to be Q{sub {beta}}{sub {beta}}({sup 130}Te)=2527.518(13) keV. This is a factor of 150 more precise than the result of the AME2003 [G. Audi et al., Nucl. Phys. A729, 337 (2003)].

Quantitative Assessment of Proliferative Effects of Oral Vanadium on Pancreatic Islet Volumes and Beta Cell Numbers of Diabetic Rats.

PubMed

Pirmoradi, Leila; Noorafshan, Ali; Safaee, Akbar; Dehghani, Gholam Abbas

2016-01-01

Oral vanadyl sulfate (vanadium) induces normoglycemia, proliferates beta cells and prevents pancreatic islet atrophy in streptozotocin-induced diabetic rats. Soteriological method is used to quantitate the proliferative effects of vanadium on beta-cell numbers and islet volumes of normal and diabetic rats. Adult male Sprague-Dawley rats were made diabetic with intravenous streptozotocin injection (40 mg/kg). Normal and diabetic rats were divided into four groups. While control normal and diabetic (CD) groups used water, vanadium-treated normal (VTN) and diabetic (VTD) groups used solutions containing vanadyl sulfate (0.5-1 mg/mL, VOSO4+5H2O). Tail blood samples were used to measure blood glucose (BG) and plasma insulin. Two months after treatment, rats were sacrificed, pancreata prepared, and stereology method was used to quantitatively evaluate total beta cell numbers (TBCN) and total islet volumes (TISVOL). Normoglycemia persisted in VTN with significantly decreased plasma insulin (0.19±0.08 vs. 0.97±0.27 ng/dL, P<0.002). The respective high BG (532±49 vs. 144±46 mg/dL, P<0.0001) and reduced plasma insulin (0.26±0.15 vs. 0.54±0.19 ng/dL, P<0.002) seen in CD were reversed in VTD during vanadium treatment or withdrawal. While the induction of diabetes, compared to their control, significantly decreased TISVOL (1.9±0.2 vs. 3.03±0.6 mm3, P<0.003) and TBCN (0.99±0.1 vs. 3.2±0.2 x 106, P<0.003), vanadium treatment significantly increased TISVOL (2.9±0.8 and 4.07±1.0 mm3, P<0.003) and TBCN (1.5±0.3 and 3.8±0.6 x 106, P<0.03). Two-month oral vanadium therapy in STZ-diabetic rats ameliorated hyperglycemia by partially restoring plasma insulin. This action was through proliferative actions of vanadium in preventing islet atrophy by increasing beta-cell numbers.

Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

PubMed

Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia; Norrild, Bodil; Prause, Jan Ulrik; Vinding, Troels; Heegaard, Steffen

2007-08-01

To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

A thymosin beta15-like peptide promotes intersegmental myotome extension in the chicken embryo.

PubMed

Chankiewitz, Verena; Morosan-Puopolo, Gabriela; Yusuf, Faisal; Rudloff, Stefan; Pröls, Felicitas; Kleff, Veronika; Hofmann, Dietrich Kurt; Brand-Saberi, Beate

2014-03-01

Beta-thymosins constitute a group of small actin-sequestering peptides. These highly conserved peptides are involved in cytoskeleton dynamics and can influence different cell properties such as motility, substrate adhesion, shape and chemotaxis. As a marker for tumour metastasis, the mammalian thymosin beta15 is believed to have an important diagnostic relevance in cancer prognosis, although little is known about its physiological function. In order to study the role of thymosin beta15(avian) in embryogenesis, we cloned the chicken and quail orthologues of thymosin beta15 and used the chicken as a model for vertebrate development. Avian thymosin beta15, the first known non-mammalian thymosin beta15-like gene, encodes a peptide that possesses a cysteine at position one after the methionine which is a significant difference compared to its mammalian counterparts. Thymosin beta15(avian) expression starts at an early stage of development. The expression pattern changes rapidly with development and differs from that of the related thymosin beta4 gene. The most prominent expression domain is seen in developing muscles of limbs and trunk. Gain-of-function experiments revealed that thymosin beta15(avian) has a function in normal myotome development. Ectopic over-expression of thymosin beta15(avian) leads to premature elongation of myotome cells trespassing segment borders. We conclude that thymosin beta15(avian) has a still undescribed function in promoting myocyte elongation.

[Establishment of the mathematic model of total quantum statistical moment standard similarity for application to medical theoretical research].

PubMed

He, Fu-yuan; Deng, Kai-wen; Huang, Sheng; Liu, Wen-long; Shi, Ji-lian

2013-09-01

The paper aims to elucidate and establish a new mathematic model: the total quantum statistical moment standard similarity (TQSMSS) on the base of the original total quantum statistical moment model and to illustrate the application of the model to medical theoretical research. The model was established combined with the statistical moment principle and the normal distribution probability density function properties, then validated and illustrated by the pharmacokinetics of three ingredients in Buyanghuanwu decoction and of three data analytical method for them, and by analysis of chromatographic fingerprint for various extracts with different solubility parameter solvents dissolving the Buyanghanwu-decoction extract. The established model consists of four mainly parameters: (1) total quantum statistical moment similarity as ST, an overlapped area by two normal distribution probability density curves in conversion of the two TQSM parameters; (2) total variability as DT, a confidence limit of standard normal accumulation probability which is equal to the absolute difference value between the two normal accumulation probabilities within integration of their curve nodical; (3) total variable probability as 1-Ss, standard normal distribution probability within interval of D(T); (4) total variable probability (1-beta)alpha and (5) stable confident probability beta(1-alpha): the correct probability to make positive and negative conclusions under confident coefficient alpha. With the model, we had analyzed the TQSMS similarities of pharmacokinetics of three ingredients in Buyanghuanwu decoction and of three data analytical methods for them were at range of 0.3852-0.9875 that illuminated different pharmacokinetic behaviors of each other; and the TQSMS similarities (ST) of chromatographic fingerprint for various extracts with different solubility parameter solvents dissolving Buyanghuanwu-decoction-extract were at range of 0.6842-0.999 2 that showed different constituents with various solvent extracts. The TQSMSS can characterize the sample similarity, by which we can quantitate the correct probability with the test of power under to make positive and negative conclusions no matter the samples come from same population under confident coefficient a or not, by which we can realize an analysis at both macroscopic and microcosmic levels, as an important similar analytical method for medical theoretical research.

Supplements of transgenic malt or grain containing (1,3-1,4)-beta-glucanase increase the nutritive value of barley-based broiler diets to that of maize.

PubMed

Von Wettstein, D; Warner, J; Kannangara, C G

2003-07-01

1. A diet with addition to normal barley of malt from transgenic barley expressing a protein engineered, thermotolerant Bacillus (1,3-1,4)-beta-glucanase during germination has previously been demonstrated to provide a broiler chicken weight gain comparable to maize diets. It also reduced dramatically the number of birds with adhering sticky droppings, but did not entirely eliminate sticky droppings. One of the objectives of the broiler chicken trials reported here was to determine if higher concentrations of transgenic malt could alleviate the sticky droppings. 2. Another aim was to investigate the feasibility of using mature transgenic grain containing the thermotolerant (1,3-1,4)-beta-glucanase as feed addition and to compare diets containing transgenic grain to a diet with the recommended amount of a commercial beta-glucanase-based product. 3. Inclusion of 75 or 151 g/kg transgenic malt containing 4.7 or 98 mg/kg thermotolerant (1,3-1,4)-beta-glucanase with 545 or 469 g/kg non-transgenic barley instead of maize yielded a weight gain in Cornish Cross broiler chickens indistinguishable from presently used maize diets. The gene encoding the enzyme is expressed in the aleurone with a barley alpha-amylase gene promoter and the enzyme is synthesised with a signal peptide for secretion into the endosperm of the malting grain. 4. Equal weight gain was achieved, when the feed included 39 g/kg transgenic barley grain [containing 66 mg/kg thermotolerant (1,3-1,4)-beta-glucanase] and 581 g/kg non-transgenic barley instead of maize. In this case, the gene encoding the enzyme has been expressed with the D-hordein gene (Hor3-1) promoter during grain maturation. The enzyme is synthesised as a precursor with a signal peptide for transport through the endoplasmic reticulum and targeted into the storage vacuoles. Deposition of the enzyme in the prolamin storage protein bodies of the endosperm protects it from degradation during the programmed cell death of the endosperm in the final stages of grain maturation and provides extraordinary heat stability. The large amount of highly active (1,3-1,4)-beta-glucanase in the mature grain allowed the reduction of the transgenic grain ingredient to 0.2 g/kg diet, thus making the ingredient comparable to that of the trace minerals added to standard diets. 5. A direct comparison using transgenic grain supplement at the level of 1 g/kg of feed with the standard recommended addition of the commercial enzyme preparation Avizyme 1100 at 1 g/kg yielded equal weight gain, feed consumption and feed efficiency in birds fed a barley-based diet. 6. The production of sticky droppings characteristic of broilers fed on barley diets was avoided with all 9 experimental diets and reduced to the level observed with a standard maize diet by supplementation with transgenic barley. 7. The excellent growth and normal survival of the 400 broilers tested on barley diets supplemented with transgenic grain or malt showed the grain and malt not to be toxic. 8. The barley feed with added transgenic grain or malt containing thermotolerant (1,3-1,4)-beta-glucanase provides an environmentally friendly alternative to enzyme additives, as it uses photosynthetic energy for production of the enzyme in the grain and thus avoids use of non-renewable energy for fermentation. The deposition of the enzyme in the protein bodies of the grain in the field makes coating procedures for stabilisation of enzyme activity superfluous. 9. Barley feed with the small amount of transgenic grain as additive to normal barley provides an alternative for broiler feed in areas where grain maize cannot be grown for climatic reasons or because of unsuitable soil and thus has to be imported.

Hemoglobin Hiroshima (β143 histidine → aspartic acid): a newly identified fast moving beta chain variant associated with increased oxygen affinity and compensatory erythremia

PubMed Central

Hamilton, Howard B.; Iuchi, Iwao; Miyaji, Takaoki; Shibata, Susumu

1969-01-01

During a survey for hemoglobinopathies in over 9000 residents of Hiroshima Prefecture, Japan, a fast moving hemoglobin was identified in eight members of three generations in a Japanese family. The abnormal hemoglobin, named Hb Hiroshima, constitutes about 50% of the total hemoglobin in hemolysates from the carriers who have a mild erythremia but are otherwise apparently clinically unaffected. All preparations of Hb Hiroshima have increased affinity for oxygen, by either tonometric or oxygen electrode determinations. At pH 7.0, the oxygen pressure, P50 required to half saturate an unfractionated hemolysate from a carrier was one-half that of Hb A, and the P50 of a purified sample containing no Hb A was one-fourth that of Hb A. The pH dependence of the oxygen equilibrium (Bohr effect) is below normal, as shown by the absolute value of the Bohr effect factor which is about half that of Hb A, in the pH range between 7.0 and 7.4. The Hill constant, n, for Hb Hiroshima between pH 7.0 and 7.4 is 2-2.4, compared to 2.8-3 for Hb A under the same conditions, indicating reduction of, but not complete abolition of heme-heme interaction. Urea dissociation and canine hybridization tests located the biochemical lesion in the beta chain. Fingerprints (Ingram), carboxypeptidase digestion, and amino acid analysis demonstrated that the substitution was at residue 143 in the beta chain, where histidine was replaced by aspartic acid. In contrast to other recently described high oxygen affinity mutants that show intact Bohr effects, all three of the major characteristics of the reversible combination of hemoglobin with oxygen (oxygen equilibrium, heme-heme interaction, and pH dependence) are affected in Hb Hiroshima. A tentative interpretation of these effects, relating structure to function, is offered in terms of recently developed models of normal hemoglobin. Images PMID:5773089

Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

PubMed

Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

2009-06-01

In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

Involvement of Smad3 phosphoisoform-mediated signaling in the development of colonic cancer in IL-10-deficient mice.

PubMed

Hachimine, Daisaku; Uchida, Kazushige; Asada, Masanori; Nishio, Akiyoshi; Kawamata, Seiji; Sekimoto, Go; Murata, Miki; Yamagata, Hideo; Yoshida, Katsunori; Mori, Shigeo; Tahashi, Yoshiya; Matsuzaki, Koichi; Okazaki, Kazuichi

2008-06-01

Chronic inflammation predisposes to cancer. Transforming growth factor (TGF)-beta, a multifunctional protein, suppresses the growth of normal colonic epithelial cells, whereas it stimulates the proliferation of cancer cells. Interleukin (IL)-10-deficient mice, which develop colitis and colorectal cancer, show an increased level of plasma TGF-beta. Although TGF-beta may be a key molecule in the development of colon cancer arising from chronic colitis in IL-10-deficient mice, the role of TGF-beta still remains unclear. TGF-beta activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), which converts the mediator Smad3 into two distinctive phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). We studied C57BL/6-IL-10-deficient mice (n=18) at 4 to 32 weeks of age. We investigated histology, and pSmad2/3L, pSmad2/3C, and p53 by immunohistochemistry. pSmad3L staining was detected in the cancer cells in all 10 mice with colonic cancer and in the epithelial cells in 7 of 12 mice with colonic dysplasia, but not in the normal or colitic mice. pSmad3c was detected without any significant difference between stages. p53 was weakly stained in a few cancer cells in 5 out of 10 mice. Smad3L signaling plays an important role in the carcinogenesis of chronic colitis in IL-10-deficient mice.

[Clinical value of combined detection of LDH, TPS, CEA and beta2-MG in patients with non- Hodgkin's lymphoma].

PubMed

Chen, Wei; Luo, Rong-cheng; Fan, Wei-wen; Ma, Shu-dong

2006-02-01

To study the clinical value of combined detection of 4 tumor markers, namely lactic dehydrogenate (LDH), tissue polypeptide specific antigen (TPS), carcinoembryonic antigen (CEA) and beta2-microglobulin (beta2-MG) in patients with non-Hodgkin's lymphoma (NHL). The serum level of LDH was determined with automatic biochemical analyzer and TPS, CEA and beta2-MG levels were determined by enzyme-linked immumosorbent assay (ELISA) in 59 patients with NHL and 40 healthy adults. The levels of the 4 tumor markers were significantly higher in NHL patients than in the healthy control subjects (P<0.05). After chemotherapy, the serum levels of TPS and beta2-MG were significantly lowered in the patients who showed favorable response to the treatment (P<0.05), but the levels of LDH and CEA showed no significant change (P>0.05). The serum levels of LDH, TPS, CEA and beta2-MG in the patients in a stable or progressive phase did had no significant changes after chemotherapy (P>0.05). Combined detection of LDH, TPS, CEA and beta2-MG can be helpful to assist diagnosis of NHL and treatment evaluation.

Bilateral Functional Connectivity of the Basal Ganglia in Patients with Parkinson’s Disease and Its Modulation by Dopaminergic Treatment

PubMed Central

Little, Simon; Tan, Huiling; Anzak, Anam; Pogosyan, Alek; Kühn, Andrea; Brown, Peter

2013-01-01

Parkinson’s disease is characterised by excessive subcortical beta oscillations. However, little is known about the functional connectivity of the two basal ganglia across hemispheres and specifically the role beta plays in this. We recorded local field potentials from the subthalamic nucleus bilaterally in 23 subjects with Parkinson’s disease at rest, on and off medication. We found suppression of low beta power in response to levodopa (t22 = −4.4, p<0.001). There was significant coherence between the two sides in the beta range in 19 of the subjects. Coherence was selectively attenuated in the low beta range following levodopa (t22 = −2.7; p = 0.01). We also separately analysed amplitude co-modulation and phase synchronisation in the beta band and found significant amplitude co-modulation and phase locking values in 17 and 16 subjects respectively, off medication. There was a dissociable effect of levodopa on these measures, with a significant suppression only in low beta phase locking value (t22 = −2.8, p = 0.01) and not amplitude co-modulation. The absolute mean values of amplitude co-modulation (0.40±0.03) and phase synchronisation (0.29±0.02) off medication were, however, relatively low, suggesting that the two basal ganglia networks may have to be approached separately with independent sensing and stimulation during adaptive deep brain stimulation. In addition, our findings highlight the functional distinction between the lower and upper beta frequency ranges and between amplitude co-modulation and phase synchronization across subthalamic nuclei. PMID:24376574

IL-1beta, IL-6 and IL-8 levels in gyneco-obstetric infections.

PubMed Central

Basso, Beatriz; Giménez, Francisco; López, Carlos

2005-01-01

OBJECTIVE: During pregnancy cytokines and inflammatory mediators stimulate the expression of prostaglandin, the levels of which determine the onset of labor. The aim of this work was to study interleukin IL-1beta, IL-6 and IL-8 levels in the vaginal discharge, serum and urine of pregnant women with genitourinary infection before and after specific treatment. One hundred and fifty-one patients were studied during the second or third trimester of their pregnancy. METHODS: The selected patients were: healthy or control group (n = 52), those with bacterial vaginosis (n = 47), those with vaginitis (n = 37), those with asymptomatic urinary infection (n = 15) and post-treatment. The level of cytokines was assayed by ELISA test. The Mann-Whitney U-test was used for statistical analysis. RESULTS: The IL-1beta levels in vaginal discharge were: control 103.5 +/- 24.2 pg/ml, bacterial vaginosis 1030 +/- 59.5, vaginitis 749.14 +/- 66.7l ( p < 0.0001), post-treatment 101.4 +/- 28.7. IL-6 values were similar in both control and infected groups, and there were no patients with chorioamnionitis. In vaginal discharge IL-6: control 14.2 +/- 3.9 pg/ml, bacterial vaginosis 13.2 +/- 3.8, vaginitis 13 +/- 4.2. IL-8 levels were: control 1643 +/- 130.3 pg/ml, bacterial vaginosis 2612.7 +/- 257.7, vaginitis 3437 +/- 460 (p < 0.0001), post-treatment 1693 +/- 126.6. In urine the results were: control 40.2 +/- 17 pg/ml, asymptomatic urinary infection 1200.7 +/- 375 (p < 0.0001). In patients with therapeutic success both IL-1beta and IL-8 returned to normal levels. CONCLUSIONS: Genitourinary infections induce a significant increase in IL-1beta and IL-8 levels in vaginal secretions, and IL-8 in urine as well. Both cytokines could be useful as evolutive markers of infection. PMID:16338780

Mantle plumes on Venus revisited

NASA Technical Reports Server (NTRS)

Kiefer, Walter S.

1992-01-01

The Equatorial Highlands of Venus consist of a series of quasicircular regions of high topography, rising up to about 5 km above the mean planetary radius. These highlands are strongly correlated with positive geoid anomalies, with a peak amplitude of 120 m at Atla Regio. Shield volcanism is observed at Beta, Eistla, Bell, and Atla Regiones and in the Hathor Mons-Innini Mons-Ushas Mons region of the southern hemisphere. Volcanos have also been mapped in Phoebe Regio and flood volcanism is observed in Ovda and Thetis Regiones. Extensional tectonism is also observed in Ovda and Thetis Regiones. Extensional tectonism is also observed in many of these regions. It is now widely accepted that at least Beta, Atla, Eistla, and Bell Regiones are the surface expressions of hot, rising mantel plumes. Upwelling plumes are consistent with both the volcanism and the extensional tectonism observed in these regions. The geoid anomalies and topography of these four regions show considerable variation. Peak geoid anomalies exceed 90 m at Beta and Atla, but are only 40 m at Eistla and 24 m at Bell. Similarly, the peak topography is greater at Beta and Atla than at Eistla and Bell. Such a range of values is not surprising because terrestrial hotspot swells also have a side range of geoid anomalies and topographic uplifts. Kiefer and Hager used cylindrical axisymmetric, steady-state convection calculations to show that mantle plumes can quantitatively account for both the amplitude and the shape of the long-wavelength geoid and topography at Beta and Atla. In these models, most of the topography of these highlands is due to uplift by the vertical normal stress associated with the rising plume. Additional topography may also be present due to crustal thickening by volcanism and crustal thinning by rifting. Smrekar and Phillips have also considered the geoid and topography of plumes on Venus, but they restricted themselves to considering only the geoid-topography ratio and did not examine either the geoid and topography amplitudes separately or the shapes of anomalies.

High-beta steady-state research with integrated modeling in the JT-60 Upgrade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozeki, T.

2007-05-15

Improvement of high-beta performance and its long sustainment was obtained with ferritic steel tiles in the JT-60 Upgrade (JT-60U) [T. Fujita et al., Phys. Plasmas 50, 104 (2005)], which were installed inside the vacuum vessel to reduce fast ion loss by decreasing the toroidal field ripple. When a separation between the plasma surface and the wall was small, high-beta plasmas reached the ideal wall stability limit, i.e., the ideal magnetohydrodynamics stability limit with the wall stabilization. A small rotation velocity of 0.3% of the Alfven velocity was found to be effective for suppressing the resistive wall mode. Sustainment of themore » high normalized beta value of {beta}{sub N}=2.3 has been extended to 28.6 s ({approx}15 times the current diffusion time) by improvement of the confinement and increase in the net heating power. Based on the research in JT-60U experiments and first-principle simulations, integrated models of core, edge-pedestal, and scrape-off-layer (SOL) divertors were developed, and they clarified complex features of reactor-relevant plasmas. The integrated core plasma model indicated that the small amount of electron cyclotron (EC) current density of about half the bootstrap current density could effectively stabilize the neoclassical tearing mode by the localized EC current accurately aligned to the magnetic island center. The integrated edge-pedestal model clarified that the collisionality dependence of energy loss due to the edge-localized mode was caused by the change in the width of the unstable mode and the SOL transport. The integrated SOL-divertor model clarified the effect of the exhaust slot on the pumping efficiency and the cause of enhanced radiation near the X-point multifaceted asymmetric radiation from edge. Success in these consistent analyses using the integrated code indicates that it is an effective means to investigate complex plasmas and to control the integrated performance.« less

Magnetic ramp scale at supercritical perpendicular collisionless shocks: Full particle electromagnetic simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Zhongwei; SOA Key Laboratory for Polar Science, Polar Research Institute of China, Shanghai, 200136; Lu, Quanming

2013-09-15

Supercritical perpendicular collisionless shocks are known to exhibit foot, ramp, and overshoot structures. The shock ramp structure is in a smaller scale in contrast to other microstructures (foot and overshoot) within the shock front. One-dimensional full particle simulations of strictly perpendicular shocks over wide ranges of ion beta β{sub i}, Alfvén Mach number M{sub A}, and ion-to-electron mass ratio m{sub i}/m{sub e} are presented to investigate the impact of plasma parameters on the shock ramp scale. Main results are (1) the ramp scale can be as small as several electron inertial length. (2) The simulations suggest that in a regimemore » below the critical ion beta value, the shock front undergoes a periodic self-reformation and the shock ramp scale is time-varying. At higher ion beta values, the shock front self-reformation is smeared. At still higher ion beta value, the motion of reflected ions is quite diffuse so that they can lead to a quasi-steady shock ramp. Throughout the above three conditions, the shock ramp thickness increases with β{sub i}. (3) The increase (decrease) in Mach number and the decrease (increase) in the beta value have almost equivalent impact on the state (i.e., stationary or nonstationary) of the shock ramp. Both of front and ramp thicknesses are increased with M{sub A}.« less

Progressive loss of sensitivity to growth control by retinoic acid and transforming growth factor-beta at late stages of human papillomavirus type 16-initiated transformation of human keratinocytes.

PubMed

Creek, K E; Geslani, G; Batova, A; Pirisi, L

1995-01-01

Retinoids (vitamin A and its natural and synthetic derivatives) have shown potential as chemopreventive agents, and diets poor in vitamin A and/or its precursor beta-carotene have been linked to an increased risk of cancer at several sites including the cervix. Human papillomavirus (HPV) plays an important role in the etiology of cervical cancer. We have developed an in vitro model of cancer progression using human keratinocytes (HKc) immortalized by HPV16 DNA (HKc/HPV16). Although immortal, early passage HKc/HPV16, like normal HKc, require epidermal growth factor (EGF) and bovine pituitary extract (BPE) for proliferation and undergo terminal differentiation in response to serum and calcium. However, following prolonged culture, growth factor independent HKc/HPV16 lines that no longer require EGF and BPE can be selected (HKc/GFI). Further selection of HKc/GFI produces lines that are resistant to serum- and calcium- induced terminal differentiation (HKc/DR). HKc/DR, but not early passage HKc/HPV16, are susceptible to malignant conversion following transfection with viral Harvey ras or Herpes simplex virus type II DNA. We have investigated the sensitivity of low to high passage HKc/HPV16 and HKc/GFI to growth control by all-trans-retinoic acid (RA, an active metabolite of vitamin A). Early passage HKc/HPV16 are very sensitive to growth inhibition by RA, and in these cells RA decreases the expression of the HPV16 oncogenes E6 and E7. However, as the cells progress in culture they lose their sensitivity to RA. Growth inhibition by RA may be mediated through the cytokine transforming growth factor-beta (TGF-beta), a potent inhibitor of epithelial cell proliferation. RA treatment of HKc/HPV16 and HKc/GFI results in a dose-and time-dependent induction (maximal of 3-fold) in secreted levels of TGF-beta. Also, Northern blot analysis of mRNA isolated from HKc/HPV16 demonstrated that RA treatment induced TGF-beta 1 and TGF-beta 2 expression about 3- and 50-fold, respectively. We next studied the effect of TGF-beta 1 and TGF-beta 2 on the proliferation of early to late passage HKc/HPVa6, HKc/GFI and HKc/DR. While early passage HKc/HPV16 were as sensitive as normal HKc to growth inhibition by TGF-beta 1 and TGF-beta 2, the cells became increasingly resistant to TGF-beta during in vitro progression, with the proliferation of HKc/DR being virtually unaffected by TGF-beta 1 or TGF-beta 2 treatment. Overall, loss of growth inhibition by RA parallels loss of TGF-beta sensitivity.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.

PubMed

Wheeldon, N M; McDevitt, D G; Lipworth, B J

1994-08-01

1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2-adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative basis for component factors of gas flow proportional counting efficiencies

NASA Astrophysics Data System (ADS)

Nichols, Michael C.

This dissertation investigates the counting efficiency calibration of a gas flow proportional counter with beta-particle emitters in order to (1) determine by measurements and simulation the values of the component factors of beta-particle counting efficiency for a proportional counter, (2) compare the simulation results and measured counting efficiencies, and (3) determine the uncertainty of the simulation and measurements. Monte Carlo simulation results by the MCNP5 code were compared with measured counting efficiencies as a function of sample thickness for 14C, 89Sr, 90Sr, and 90Y. The Monte Carlo model simulated strontium carbonate with areal thicknesses from 0.1 to 35 mg cm-2. The samples were precipitated as strontium carbonate with areal thicknesses from 3 to 33 mg cm-2 , mounted on membrane filters, and counted on a low background gas flow proportional counter. The estimated fractional standard deviation was 2--4% (except 6% for 14C) for efficiency measurements of the radionuclides. The Monte Carlo simulations have uncertainties estimated to be 5 to 6 percent for carbon-14 and 2.4 percent for strontium-89, strontium-90, and yttrium-90. The curves of simulated counting efficiency vs. sample areal thickness agreed within 3% of the curves of best fit drawn through the 25--49 measured points for each of the four radionuclides. Contributions from this research include development of uncertainty budgets for the analytical processes; evaluation of alternative methods for determining chemical yield critical to the measurement process; correcting a bias found in the MCNP normalization of beta spectra histogram; clarifying the interpretation of the commonly used ICRU beta-particle spectra for use by MCNP; and evaluation of instrument parameters as applied to the simulation model to obtain estimates of the counting efficiency from simulated pulse height tallies.

Ap4A and ADP-beta-S binding to P2 purinoceptors present on rat brain synaptic terminals.

PubMed Central

Pintor, J.; Díaz-Rey, M. A.; Miras-Portugal, M. T.

1993-01-01

1. Diadenosine tetraphosphate (Ap4A) a dinucleotide stored and released from rat brain synaptic terminals presents two types of affinity binding sites in synaptosomes. When [3H]-Ap4A was used for binding studies a Kd value of 0.10 +/- 0.014 nM and a Bmax value of 16.6 +/- 1.2 fmol mg-1 protein were obtained for the high affinity binding site from the Scatchard analysis. The second binding site, obtained by displacement studies, showed a Ki value of 0.57 +/- 0.09 microM. 2. Displacement of [3H]-Ap4A by non-labelled Ap4A and P2-purinoceptor ligands showed a displacement order of Ap4A > adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) > 5'-adenylyl-imidodiphosphate (AMP-PNP) > alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP) in both sites revealed by the Ki values of 0.017 nM, 0.030 nM, 0.058 nM and 0.147 nM respectively for the high affinity binding site and values of 0.57 microM, 0.87 microM, 2.20 microM and 4.28 microM respectively for the second binding site. 3. Studies of the P2-purinoceptors present in synaptosomes were also performed with [35S]-ADP-beta-S. This radioligand showed two binding sites the first with Kd and Bmax values of 0.11 +/- 0.022 nM and 3.9 +/- 2.1 fmol mg-1 of protein respectively for the high affinity binding site obtained from the Scatchard plot. The second binding site showed a Ki of 0.018 +/- 0.0035 microM obtained from displacement curves. 4. Competition studies with diadenosine polyphosphates of [35S]-ADP-beta-S binding showed a displacement order of Ap4A > Ap5A > Ap6A in the high affinity binding site and Ki values of 0.023 nM, 0.081 nM and 5.72 nM respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8485620

The physiology of rodent beta-cells in pancreas slices.

PubMed

Rupnik, M

2009-01-01

Beta-cells in pancreatic islets form complex syncytia. Sufficient cell-to-cell electrical coupling seems to ensure coordinated depolarization pattern and insulin release that can be further modulated by rich innervation. The complex structure and coordinated action develop after birth during fast proliferation of the endocrine tissue. These emergent properties can be lost due to various reasons later in life and can lead to glucose intolerance and diabetes mellitus. Pancreas slice is a novel method of choice to study the physiology of beta-cells still embedded in their normal cellulo-social context. I present major advantages, list drawbacks and provide an overview on recent advances in our understanding of the physiology of beta-cells using the pancreas slice approach.

Comparison of the canine and human acid {beta}-galactosidase gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahern-Rindell, A.J.; Kretz, K.A.; O`Brien, J.S.

Several canine cDNA libraries were screened with human {beta}-galactosidase cDNA as probe. Seven positive clones were isolated and sequenced yielding a partial (2060 bp) canine {beta}-galactosidase cDNA with 86% identity to the human {beta}-galactosidase cDNA. Preliminary analysis of a canine genomic library indicated conservation of exon number and size. Analysis by Northern blotting disclosed a single mRNA of 2.4 kb in fibroblasts and liver from normal dogs and dogs affected with GM1 gangliosidosis. Although incomplete, these results indicate canine GM1 gangliosidosis is a suitable animal model of the human disease and should further efforts to devise a gene therapy strategymore » for its treatment. 20 refs., 2 figs., 1 tab.« less

Antioxidant activity of beta-blockers: an effect mediated by scavenging reactive oxygen and nitrogen species?

PubMed

Gomes, Ana; Costa, David; Lima, José L F C; Fernandes, Eduarda

2006-07-01

The therapeutic effects of beta-blockers are normally explained by their capacity to block the beta-adrenoceptors, however, some of the beneficial cardiovascular effects shown by this group of compounds have already been associated with the antioxidant properties that some of them seem to possess. The beta-blockers atenolol, labetalol, metoprolol, pindolol, propranolol, sotalol, timolol, and carvedilol were tested for their putative scavenging activity for ROS (O(2)(-), H(2)O(2), HO(.), HOCl, and ROO(.)) and RNS ((.)NO and ONOO(-)). Some of the studied compounds are effective ROS and/or RNS scavengers, these effects being possibly useful in preventing oxidative damage verified in hypertension as well as in other cardiovascular diseases that frequently emerge in association with oxidative stress.

Linear solvation energy relationships: 36. Molecular properties governing solubilities of organic nonelectrolytes in water.

PubMed

Kamlet, M J; Doherty, R M; Abboud, J L; Abraham, M H; Taft, R W

1986-04-01

Molar solubilities of non-hydrogen bond donor and weak hydrogen bond donor liquid aliphatic solutes in water, or the nearly equivalent quantities, Sg/Kgw, where Kgw is the gas-water partition coefficient and Sg is the solute concentration in the solute saturated vapor (Sg = Patm/24.5) are well correlated by the equation: log Sw congruent to log (Sg/Kgw) = 0.54 - 3.32V/100 + 0.46 pi* + 5.17 (beta or beta m) (at 25 degrees C) n = 105, r = 0.9954, SD = 0.137 V is the solute molar volume (the molecular weight divided by the liquid density at 20 degrees C), and pi* and beta are the solvatochromic parameters that are measures of solute dipolarity-polarizability and hydrogen bond acceptor basicity. The equation, which applies to liquid monofunctional aliphatic solutes is used to calculate additional new beta and beta m values. The beta m values, which are intended to apply to self-associated compounds when acting as "monomer" solutes, are: methanol, 0.42; all primary alkanols, 0.45; all secondary alkanols, 0.51; and all tertiary alkanols, 0.57.

Identification and characterization of a human smad3 splicing variant lacking part of the linker region.

PubMed

Kjellman, Christian; Honeth, Gabriella; Järnum, Sofia; Lindvall, Magnus; Darabi, Anna; Nilsson, Ingar; Edvardsen, Klaus; Salford, Leif G; Widegren, Bengt

2004-03-03

Smad3 is one of the signal transducers that are activated in response to transforming growth factor-beta (TGF-beta). We have identified and characterized a splicing variant of smad3. The splicing variant (smad3-Delta3) lacks exon 3 resulting in a truncated linker region. We could detect mRNA expression of smad3-Delta3 in all investigated human tissues. Real-time PCR analyses demonstrated that the fraction of smad3-Delta3 mRNA compared to normal smad3 varies between tissues. The amount of spliced mRNA was estimated to represent 0.5-5% of the normal smad3 mRNA. When smad3-Delta3 is overexpressed in a fibrosarcoma cell line, the Smad3-Delta3 is translocated to the nucleus upon TGF-beta stimulation and binds the Smad responsive element. Using a CAGA luciferase reporter system, we demonstrate that Smad3-Delta3 has transcriptional activity and we conclude that Smad3-Delta3 possesses functional transactivating properties.

[Changes in levels of chorionic gonadotrophin (hCG) and its subunit alpha and beta in pregnancy complicated by diabetes (GDM)].

PubMed

Olszewski, J; Szczurowicz, A; Wójcikowski, C

1995-02-01

The aim of the study was estimation of endocrinological function of placenta in pregnancy complicated by GDM. The study were performed on a group 13 women with GDM and 14 women in normal pregnancy. All women with GDM were treat by diet and intensive insulinotherapy with self monitoring levels of glucose. In women with GDM level of fructosamine and HbAlc were significant higher but in normal range. In 28 and 36 week of pregnancy were determined levels of hCG, alpha hCG, beta hCG, in serum. Level of hCG in control group and in women with GDM were respectively 97.29 U/ml vs. 29.29 U/ml, p < 0.01 in 28 week of pregnancy and 77.23 U/ml vs. 37.93 U/ml, p < 0.05 in 36 week. Level of alpha hCG was lower and beta hCG was higher in group with GDM.

LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

PubMed

Amsterdam, Abraham; Raanan, Calanit; Schreiber, Letizia; Polin, Nava; Givol, David

2013-04-05

Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Generating Low Beta Regions with Quadrupoles for Final Muon Cooling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acosta, J. G.; Cremaldi, L. M.; Hart, T. L.

2017-05-01

Muon beams and colliders are rich sources of new physics, if muons can be cooled. A normalized rms transverse muon emittance of 280 microns has been achieved in simulation with short solenoids and a betatron function of 3 cm. Here we use ICOOL, G4beamline, and MAD-X to explore using a 400 MeV/c muon beam and strong focusing quadrupoles to approach a normalized transverse emittance of 100 microns and finish 6D muon cooling. The low beta regions produced by the quadrupoles are occupied by dense, low Z absorbers, such as lithium hydride or beryllium, that cool the beam. Equilibrium transverse emittancemore » is linearly proportional to the beta function. Reverse emittance exchange with septa and/or wedges is then used to decrease transverse emittance from 100 to 25 microns at the expense of longitudinal emittance for a high energy lepton collider. Work remains to be done on chromaticity correction.« less

CLIC4 Moves Into Nucleus to Stabilize Anti-Growth Signal | Center for Cancer Research

Cancer.gov

In cancer, the delicate balance of signaling pathways that control cell growth and function is disrupted. One signaling pathway commonly altered in cancer is the TGF-beta pathway. TGF-beta significantly inhibits growth of normal cells, particularly epithelial cells. Many cancer cells have developed ways to bypass one or more steps of this pathway in order to achieve uncontrolled growth.

CLIC4 Moves Into Nucleus to Stabilize Anti-Growth Signal | Center for Cancer Research

Cancer.gov

In cancer, the delicate balance of signaling pathways that control cell growth and function is disrupted. One signaling pathway commonly altered in cancer is the TGF-beta pathway. TGF-beta significantly inhibits growth of normal cells, particularly epithelial cells. Many cancer cells have developed ways to bypass one or more steps of this pathway in order to achieve

Calculation of Free-Atom Fractions in Hydrocarbon-Fueled Rocket Engine Plume

NASA Technical Reports Server (NTRS)

Verma, Satyajit

2006-01-01

Free atom fractions (Beta) of nine elements are calculated in the exhaust plume of CH4- oxygen and RP-1-oxygen fueled rocket engines using free energy minimization method. The Chemical Equilibrium and Applications (CEA) computer program developed by the Glenn Research Center, NASA is used for this purpose. Data on variation of Beta in both fuels as a function of temperature (1600 K - 3100 K) and oxygen to fuel ratios (1.75 to 2.25 by weight) is presented in both tabular and graphical forms. Recommendation is made for the Beta value for a tenth element, Palladium. The CEA computer code was also run to compare with experimentally determined Beta values reported in literature for some of these elements. A reasonable agreement, within a factor of three, between the calculated and reported values is observed. Values reported in this work will be used as a first approximation for pilot rocket engine testing studies at the Stennis Space Center for at least six elements Al, Ca, Cr, Cu, Fe and Ni - until experimental values are generated. The current estimates will be improved when more complete thermodynamic data on the remaining four elements Ag, Co, Mn and Pd are added to the database. A critique of the CEA code is also included.

Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts.

PubMed

Lee, K H; Song, S U; Hwang, T S; Yi, Y; Oh, I S; Lee, J Y; Choi, K B; Choi, M S; Kim, S J

2001-09-20

Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popp, R.A.; Popp, D.M.; Johnson, F.M.

Mice homozygous for a spontaneous mutation, in which the ..beta..-major globin gene is deleted, have clinical symptoms of ..beta..-thalassemia. These mice have a hypocellular, hypochromic, microcytic anemia that becomes more severe with increasing age. The defective red cell morphology, decreased osmotic fragility of erythrocytes and shortened red cell life span found in ..beta..-thalassemic mice are similar to those observed in human ..beta..-thalassemia. Synthesis of ..beta..-globin is depressed but not as much as might be expected because the expression of the..beta..-minor globin gene is enhanced to encode two to three times more globin than in normal mice. Splenomegaly, an enlarged poolmore » of stem cells for erythropoiesis, and iron overloading occur in older mice. The fact that these mice remain moderately healthy makes them a very suitable animal model in which to develop and test alternative techniques of gene therapy that could be successfully applied to the treatment of human thalassemia. Homozygous ..beta..-thalassemic mice have large deposits of iron in their tissues, which might make these mice also useful for in vivo tests of the effectiveness and possible long-term side effects for newly developed iron chelators.« less

TGF-beta antisense oligonucleotides reduce mRNA expression of matrix metalloproteinases in cultured wound-healing-related cells.

PubMed

Philipp, Katrin; Riedel, Frank; Germann, Günter; Hörmann, Karl; Sauerbier, Michael

2005-02-01

The pathology of chronic dermal ulcers is characterized by excessive proteolytic activity which degrades extracellular matrix. The transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta. We investigated the effect of TGF-beta antisense oligonucleotides on the mRNA expression of matrix metalloproteinases in cultured human keratinocytes, fibroblasts and endothelial cells using multiplex RT-PCR. The treatment of keratinocytes and fibroblasts with TGF-beta antisense oligonucleotides resulted in a significant decrease of expression of mRNA of MMP-1 and MMP-9 compared to controls. Accordingly, a decreased expression of MMP-1 mRNA in endothelial cells was detectable. Other MMPs were not affected. Affecting all dermal wound-healing-related cell types, TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in chronic wounds. Pharmaceutical intervention in this area ultimately may help clinicians to proactively intervene in an effort to prevent normal wounds from becoming chronic.

The 60 kDa heat shock proteins in the hyperthermophilic archaeon Sulfolobus shibatae.

PubMed

Kagawa, H K; Osipiuk, J; Maltsev, N; Overbeek, R; Quaite-Randall, E; Joachimiak, A; Trent, J D

1995-11-10

One of the most abundant proteins in the hyperthermophilic archaeon Sulfolobus shibatae is the 59 kDa heat shock protein (TF55) that is believed to form a homo-oligomeric double ring complex structurally similar to the bacterial chaperonins. We discovered a second protein subunit in the S. shibatae ring complex (referred to as alpha) that is stoichiometric with TF55 (renamed beta). The gene and flanking regions of alpha were cloned and sequenced and its inferred amino acid sequence has 54.4% identity and 74.4% similarity to beta. Transcription start sites for both alpha and beta were mapped and three potential transcription regulatory regions were identified. Northern analyses of cultures shifted from normal growth temperatures (70 to 75 degrees C) to heat shock temperatures (85 to 90 degrees C) indicated that the levels of alpha and beta mRNAs increased during heat shock, but at all temperatures their relative proportions remained constant. Monitoring protein synthesis by autoradiography of total proteins from cultures pulse labeled with L(-)[35S]methionine at normal and heat shock temperatures indicated significant increases in alpha and beta synthesis during heat shock. Under extreme heat shock conditions (> or = 90 degrees C) alpha and beta appeared to be the only two proteins synthesized. The purified alpha and beta subunits combined to form high molecular mass complexes with similar mobilities on native polyacrylamide gels to the complexes isolated directly from cells. Equal proportions of the two subunits gave the greatest yield of the complex, which we refer to as a "rosettasome". It is argued that the rosettasome consists of two homo-oligomeric rings; one of alpha and the other of beta. Polyclonal antibodies against alpha and beta from S. shibatae cross-reacted with proteins of similar molecular mass in 10 out of the 17 archaeal species tested, suggesting that the two rosettasome proteins are highly conserved among the archaea. The archaeal sequences were aligned with bacterial and eukaryotic chaperonins to generate a phylogenetic tree. The tree reveals the close relationship between the archaeal rosettasomes and the eukaryotic TCP1 protein family and the distant relationship to the bacterial GroEL/HSP60 proteins.

The role of the atrial electromechanical delay in predicting atrial fibrillation in beta-thalassemia major patients.

PubMed

Rago, Anna; Russo, Vincenzo; Papa, Andrea Antonio; Ciardiello, Carmine; Pannone, Bruno; Mayer, Maria Carolina; Cimmino, Giovanni; Nigro, Gerardo

2017-03-01

Paroxysmal atrial tachyarrhythmias frequently occur in beta-thalassemia major (β-TM) patients. The aim of the current study was to evaluate the atrial electromechanical delay (AEMD) in a large β-TM population with normal cardiac function and its relationship to atrial fibrillation (AF) onset. Eighty β-TM patients (44 men, 36 women), with a mean age of 36.2 ± 11.1 years, and 80 healthy subjects used as controls, matched for age and gender, were studied for the occurrence of AF during a 5-year follow-up, through 30-day external loop recorder (ELR) monitoring performed every 6 months. Intra-AEMD and inter-AEMD of both atria were measured through tissue Doppler echocardiography. P-wave dispersion (PD) was carefully measured using 12-lead electrocardiogram (ECG). Compared to the healthy control group, the β-TM patients showed a statistically significant increase in inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD. Dividing the β-TM group into two subgroups (patients with or without AF), the inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD were significantly higher in the subgroup with AF compared to the subgroup without AF. There were significant good correlations of intra-left AEMD and inter-AEMD with PD. A cut-off value of 40.1 ms for intra-left AEMD had a sensitivity of 76.2% and a specificity of 97.5% in identifying β-TM patients with AF risk. A cut-off value of 44.8 ms for inter-AEMD had a sensitivity of 81.2% and a specificity of 98.7% in identifying this category of patients. Our results showed that the echocardiographic atrial electromechanical delay indices (intra-left and inter-AEMD) and the PD were significantly increased in β-TM subjects with normal cardiac function. PD and AEMD represent non-invasive, inexpensive, useful, and simple parameters to assess the AF risk in β-TM patients.

Effects of fast ions on interchange modes in the Large Helical Device plasmas

NASA Astrophysics Data System (ADS)

Pinon, Jonhathan; Todo, Yasushi; Wang, Hao

2018-07-01

Effects of fast ions on the magnetohydrodynamic (MHD) instabilities in a Large Helical Device (LHD) plasma with the central beta value (=pressure normalized by the magnetic pressure) 4% have been investigated with hybrid simulations for energetic particles interacting with an MHD fluid. When fast ions are neglected, it is found that the dominant instability is an ideal interchange mode with the dominant harmonic m/n = 2/1, where m, n are respectively the poloidal and toroidal numbers. The spatial peak location of the m/n = 2/1 harmonic is close to the ι = 1/2 magnetic surface located at r/a = 0.29, where ι is the rotational transform and r/a is the normalized radius. The second unstable mode is a resistive interchange mode with m/n =3/2 that peaks at r/a = 0.65 nearby the ι = 2/3 surface, which grows more slowly than the m/n = 2/1 mode. The nonlinear coupling of the m/n = 3/2 and 2/1 mode results in the growth of the m/n = 5/3 mode and other modes leading to the global reduction and flattening of the pressure profile. When fast ions are considered with the central beta value 0.2% and the total pressure profile is kept the same, the ideal interchange mode with m/n = 2/1 located close to the plasma center is stabilized while the resistive interchange mode with m/n = 3/2 located far from the plasma center is less affected. The stabilization is attributed to the reduction of bulk pressure gradient, which is the dilution of the free energy source, because the energy transfer between the fast ions and the interchange modes is found to be negligible. For higher fast-ion pressure, Alfvén eigenmodes are destabilized by fast ions.

Serum oestradiol and beta-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome.

PubMed

Kumbak, Banu; Oral, Engin; Karlikaya, Guvenc; Lacin, Selman; Kahraman, Semra

2006-10-01

The aim of this study was to assess the clinical value of serum oestradiol concentration 8 days after embryo transfer (D8E2) and beta-human chorionic gonadotrophin (HCG-beta) concentration 12 days after embryo transfer (D12HCG-beta) in the prediction of pregnancy and the outcome of pregnancy following assisted reproduction, taking into account the day of transfer, which was either day 3 (D3) or day 5 (D5). The objective was to improve patient counselling by giving quantitative and reliable predictive information instead of non-specific uncertainties. A total of 2035 embryo transfer cycles performed between January 2003 and June 2005 were analysed retrospectively. Biochemical pregnancy, ectopic pregnancy and first-trimester abortions were classified as non-viable pregnancies; pregnancies beyond 12 weeks gestation were classified as ongoing pregnancies (OP). Significantly higher D8E2 and D12HCG-beta were obtained in D5 transfers compared with D3 transfers with regard to pregnancy and OP (P

Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice.

PubMed

Hamelet, J; Aït-Yahya-Graison, E; Matulewicz, E; Noll, C; Badel-Chagnon, A; Camproux, A-C; Demuth, K; Paul, J-L; Delabar, J M; Janel, N

2007-12-01

Hyperhomocysteinaemia is a metabolic disorder associated with the development of premature atherosclerosis. Among the determinants which predispose to premature thromboembolic and atherothrombotic events, serum activity of paraoxonase 1, mainly synthesized in the liver, has been shown to be a predictor of cardiovascular disease and to be negatively correlated with serum homocysteine levels in human. Even though treatments of hyperhomocysteinaemic patients ongoing cardiovascular complications are commonly used, it still remains unclear above which homocysteine level a preventive therapy should be started. In order to establish a threshold of plasma homocysteine concentration we have analyzed the hepatic cystathionine beta synthase and paraoxonase 1 activities in a moderate to intermediate murine model of hyperhomocysteinaemia. Using wild type and heterozygous cystathionine beta synthase deficient mice fed a methionine enriched diet or a control diet, we first studied the link between cystathionine beta synthase and paraoxonase 1 activities and plasma homocysteine concentration. Among the animals used in this study, we observed a negative correlation between plasma homocysteine level and cystathionine beta synthase activity (rho=-0.52, P=0.0008) or paraoxonase 1 activity (rho=-0.49, P=0.002). Starting from these results, a homocysteine cut-off value of 15 microm has been found for both cystathionine beta synthase (P=0.0003) and paraoxonase 1 (P=0.0007) activities. Our results suggest that both cystathionine beta synthase and paraoxonase 1 activities are significantly decreased in mice with a plasma homocysteine value greater than 15 microm. In an attempt to set up preventive treatment for cardiovascular disease our results indicate that treatments should be started from 15 microm of plasma homocysteine.

Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with 68Ga-DOTA-octreotide: a potential PET tracer for beta cell mass measurement.

PubMed

Sako, Takeo; Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky; Senda, Michio; Watanabe, Yasuyoshi

2013-12-06

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with (68)Gallium ((68)Ga). After intravenous injection of (68)Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that (68)Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of (68)Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with (68)Ga-DOTA-octreotide could be a potential tool for evaluating BCM. Copyright © 2013 Elsevier Inc. All rights reserved.

Biochemical properties of beta-glucosidase in leukocytes from patients and obligated heterozygotes for Gaucher disease carriers.

PubMed

Michelin, Kristiane; Wajner, Alessandro; Bock, Hugo; Fachel, Angela; Rosenberg, Roberto; Pires, Ricardo Flores; Pereira, Maria Luiza Saraiva; Giugliani, Roberto; Coelho, Janice Carneiro

2005-12-01

Gaucher's disease (GD) is a disorder caused by the deficiency of lysosomal beta-glucosidase, an enzyme that participates in the degradation of glycosphingolipids. Deficiency of this enzyme results in the storage of glucocerebrosides in lysosomes of macrophage. No studies are available in the literature comparing biochemical and kinetic behavior of this enzyme in leukocytes and fibroblasts from normal individuals, obligate heterozygotes and patients with GD. The behavior of beta-glu in terms of optimum pH, heat stability, Km and Vmax in leukocytes from patients with GD and obligated heterozygotes with different genotypes and normal individuals were characterized. Optimum pH was similar in all groups analyzed. In terms of Km and Vmax, several differences among heterozygotes and homozygotes groups and among these groups and normal enzyme were observed. Enzyme from all groups were inactivated when preincubated at 60 degrees C, but some enzymes were more stable than other. Results showed a different behavior of the enzyme in the 3 groups under analysis. Such behavior varied according to individual mutation. The catalytic gradient presented by beta-glu allowed the correlation of N370S mutation-which presented more stable biochemical properties-with the non-neurological clinical condition of the disease and the catalytically less stable mutation (D409H), with the neurological clinical condition of GD. This study contributes to a better understanding of the repercussion of the different mutations on the protein function, thus allowing to predict the severity of such complex metabolic disorder and to anticipate the most appropriate intervention for each case specifically.

Primary defect of congenital dyserythropoietic anemia type II. Failure in glycosylation of erythrocyte lactosaminoglycan proteins caused by lowered N-acetylglucosaminyltransferase II.

PubMed

Fukuda, M N; Dell, A; Scartezzini, P

1987-05-25

Congenital dyserythropoietic anemia type II or hereditary erythroblastic multinuclearity with positive acidified serum test (HEMPAS) is a genetic disease caused by membrane abnormality. Previously we have found that Band 3 and Band 4.5 are not glycosylated by lactosaminoglycans in HEMPAS erythrocytes, whereas normally these proteins have lactosaminoglycans (Fukuda, M. N., Papayannopoulou, T., Gordon-Smith, E. C., Rochant, H., and Testa, U. (1984) Br. J. Haematol. 56, 55-68). In order to find out where glycosylation of lactosaminoglycans stops, we have analyzed the carbohydrate structures of HEMPAS Band 3. By fast atom bombardment-mass spectrometry, methylation analysis, and hydrazinolysis followed by exoglycosidase treatments, the following structure was elucidated: (formula; see text) N-Linked glycopeptides synthesized in vitro by reticulocyte microsomes from HEMPAS were shown to be predominantly the above short oligosaccharide, whereas those from normal reticulocytes contain large molecular weight carbohydrates. The N-acetylglucosaminyltransferase II, which transfers N-acetylglucosamine to the C-2 position of the Man alpha 1----6Man beta 1----arm of the biantennary core structure, was therefore examined by using Man alpha 1----6(GlcNAc beta 1----2Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcol as an acceptor. N-Acetylglucosaminyltransferase II activity was demonstrated in the lymphocyte microsome fraction from normal individuals. However, this enzyme activity was found to be decreased in those from HEMPAS patients. These results suggest that the primary defect of HEMPAS lies in the lowered activity of N-acetylglucosaminyltransferase II.

A class-A beta-lactamase from Pseudomonas stutzeri that is highly active against monobactams and cefotaxime.

PubMed Central

Franceschini, N; Galleni, M; Frère, J M; Oratore, A; Amicosante, G

1993-01-01

A beta-lactamase produced by Pseudomonas stutzeri was purified to protein homogeneity, and its physicochemical and catalytic properties were determined. Its profile was unusual since, in addition to penicillins, the enzyme hydrolysed second- and third-generation 'beta-lactamase-stable' cephalosporins and monobactams with similar efficiencies. On the basis of the characteristics of the interaction with beta-iodopenicillanic acid, the enzyme could be classified as a class-A beta-lactamase. However, when compared with most class-A beta-lactamases, it exhibited significantly lower kcat./Km values for the compounds usually considered to be the best substrates of these enzymes. PMID:8318000

The mechanism of chromosome 7 inversion in human lymphocytes expressing chimeric gamma beta TCR.

PubMed

Retière, C; Halary, F; Peyrat, M A; Le Deist, F; Bonneville, M; Hallet, M M

1999-01-15

Functional chimeric TCR chains, encoded by V gamma J gamma C beta or V gamma J beta C beta hybrid gene TCR, are expressed at the surface of a small fraction of alpha beta T lymphocytes in healthy individuals. Their frequency is dramatically increased in patients with ataxia-telangiectasia, a syndrome associated with inherited genomic instability. As the TCR gamma and beta loci are in an inverted orientation on chromosome 7, the generation of such hybrid genes requires at least an inversion event. Until now, neither the sequences involved in this genetic mechanism nor the number of recombinations leading to the formation of functional transcriptional units have been characterized. In this manuscript, we demonstrate that at least two rearrangements, involving classical recombination signal sequence and the V(D)J recombinase complex, lead to the formation of productive hybrid genes. A primary inversion 7 event between D beta and J gamma genic segments generates C gamma V beta and C beta V gamma hybrid loci. Within the C gamma V beta locus, secondary rearrangements between V gamma and J gamma or V gamma and J beta elements generate functional genes. Besides, our results suggest that secondary rearrangements were blocked in the C beta V gamma locus of normal but not ataxia-telangiectasia T lymphocytes. We also provide formal evidence that the same D beta-3' recombination signal sequence can be used in successive rearrangements with J gamma and J beta genic segments, thus showing that a signal joint has been involved in a secondary recombination event.

Hypertrophic stimulation increases beta-actin dynamics in adult feline cardiomyocytes.

PubMed

Balasubramanian, Sundaravadivel; Mani, Santhosh K; Kasiganesan, Harinath; Baicu, Catalin C; Kuppuswamy, Dhandapani

2010-07-12

The myocardium responds to hemodynamic stress through cellular growth and organ hypertrophy. The impact of cytoskeletal elements on this process, however, is not fully understood. While alpha-actin in cardiomyocytes governs muscle contraction in combination with the myosin motor, the exact role of beta-actin has not been established. We hypothesized that in adult cardiomyocytes, as in non-myocytes, beta-actin can facilitate cytoskeletal rearrangement within cytoskeletal structures such as Z-discs. Using a feline right ventricular pressure overload (RVPO) model, we measured the level and distribution of beta-actin in normal and pressure overloaded myocardium. Resulting data demonstrated enriched levels of beta-actin and enhanced translocation to the Triton-insoluble cytoskeletal and membrane skeletal complexes. In addition, RVPO in vivo and in vitro hypertrophic stimulation with endothelin (ET) or insulin in isolated adult cardiomyocytes enhanced the content of polymerized fraction (F-actin) of beta-actin. To determine the localization and dynamics of beta-actin, we adenovirally expressed GFP-tagged beta-actin in isolated adult cardiomyocytes. The ectopically expressed beta-actin-GFP localized to the Z-discs, costameres, and cell termini. Fluorescence recovery after photobleaching (FRAP) measurements of beta-actin dynamics revealed that beta-actin at the Z-discs is constantly being exchanged with beta-actin from cytoplasmic pools and that this exchange is faster upon hypertrophic stimulation with ET or insulin. In addition, in electrically stimulated isolated adult cardiomyocytes, while beta-actin overexpression improved cardiomyocyte contractility, immunoneutralization of beta-actin resulted in a reduced contractility suggesting that beta-actin could be important for the contractile function of adult cardiomyocytes. These studies demonstrate the presence and dynamics of beta-actin in the adult cardiomyocyte and reinforce its usefulness in measuring cardiac cytoskeletal rearrangement during hypertrophic stimulation.

Caveolae are negative regulators of transforming growth factor-beta1 signaling in ureteral smooth muscle cells.

PubMed

Stehr, Maximilian; Estrada, Carlos R; Khoury, Joseph; Danciu, Theodora E; Sullivan, Maryrose P; Peters, Craig A; Solomon, Keith R; Freeman, Michael R; Adam, Rosalyn M

2004-12-01

The mechanisms underlying ureteral cell regulation are largely unknown. Previous studies have identified lipid rafts/caveolae as regulators of growth stimulatory signals in ureteral smooth muscle cells (USMCs). In this study we determined whether growth inhibitory signaling by transforming growth factor-beta1 (TGF-beta1) is also regulated by caveolae in USMC. Expression of components of the TGF-beta1 signaling axis in USMCs was determined by immunoblot and mRNA analyses. Growth regulatory activity of TGF-beta1 was assessed by H-thymidine incorporation. In select experiments caveolae were disrupted reversibly by cholesterol depletion and replenishment prior to TGF-beta1 treatment. TGF-beta1-responsive gene expression was evaluated using the TGF-beta1 responsive promoter-reporter construct 3TP-Lux. USMCs expressed TGF-beta1, types I and II TGF-beta1 receptors, and the effector Smad-2. TGF-beta1 potently inhibited DNA synthesis in USMCs (IC50 60 pM). TGF-beta1 mediated DNA synthesis inhibition was potentiated following the disruption of caveolae by cholesterol depletion. This effect was reversible with membrane cholesterol restoration. TGF-beta1 stimulated gene activity was augmented by caveolae disruption, while caveolae reformation returned promoter activity to baseline levels. TGF-beta1 is a potent growth inhibitor of USMCs and its activity can be enhanced by caveolae ablation. These findings suggest a role for TGF-beta1 in the growth regulation of normal ureteral cells and implicate caveolar membrane domains in the negative regulation of TGF-beta1 signaling. These studies may be relevant to ureteral pathologies that are characterized by smooth muscle dysplasia.

Association between educational attainment and amyloid deposition across the spectrum from normal cognition to dementia: neuroimaging evidence for protection and compensation.

PubMed

Arenaza-Urquijo, Eider M; Bejanin, Alexandre; Gonneaud, Julie; Wirth, Miranka; La Joie, Renaud; Mutlu, Justine; Gaubert, Malo; Landeau, Brigitte; de la Sayette, Vincent; Eustache, Francis; Chételat, Gaël

2017-11-01

The brain mechanisms underlying the effect of intellectual enrichment may evolve along the normal aging Alzheimer's disease (AD) cognitive spectrum and may include both protective and compensatory mechanisms. We assessed the association between early intellectual enrichment (education, years) and average cortical florbetapir standardized uptake value ratio as well as performed voxel-wise analyses in a total of 140 participants, including cognitively normal older adults, mild cognitive impairment (MCI), and AD patients. Higher education was associated with lower cortical florbetapir positron emission tomography (florbetapir-PET) uptake, notably in the frontal lobe in normal older adults, but with higher uptake in frontal, temporal, and parietal regions in MCI after controlling for global cognitive status. No association was found in AD. In MCI, we observed an increased fluorodeoxyglucose positron emission tomography (FDG-PET) uptake with education within the regions of higher florbetapir-PET uptake, suggesting a compensatory increase. Early intellectual enrichment may be associated with protection and compensation for amyloid beta (Aβ) deposition later in life, before the onset of dementia. Previous investigations have been controversial as regard to the effects of intellectual enrichment variables on Aβ deposition; the present findings call for approaches aiming to evaluate mechanisms of resilience across disease stages. Copyright © 2017 Elsevier Inc. All rights reserved.

Q Values of the Superallowed {beta} Emitters {sup 26}Al{sup m}, {sup 42}Sc, and {sup 46}V and Their Impact on V{sub ud} and the Unitarity of the Cabibbo-Kobayashi-Maskawa Matrix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eronen, T.; Elomaa, V.; Hager, U.

2006-12-08

The {beta}-decay Q{sub EC} values of the superallowed beta emitters {sup 26}Al{sup m}, {sup 42}Sc, and {sup 46}V have been measured with a Penning trap to a relative precision of better than 8x10{sup -9}. Our result for {sup 46}V, 7052.72(31) keV, confirms a recent measurement that differed from the previously accepted reaction-based Q{sub EC} value. However, our results for {sup 26}Al{sup m} and {sup 42}Sc, 4232.83(13) keV and 6426.13(21) keV, are consistent with previous reaction-based values. By eliminating the possibility of a systematic difference between the two techniques, this result demonstrates that no significant shift in the deduced value ofmore » V{sub ud} should be anticipated.« less

Is serum zinc level associated with prediabetes and diabetes?: a cross-sectional study from Bangladesh.

PubMed

Islam, Md Rafiqul; Arslan, Iqbal; Attia, John; McEvoy, Mark; McElduff, Patrick; Basher, Ariful; Rahman, Waliur; Peel, Roseanne; Akhter, Ayesha; Akter, Shahnaz; Vashum, Khanrin P; Milton, Abul Hasnat

2013-01-01

To determine serum zinc level and other relevant biological markers in normal, prediabetic and diabetic individuals and their association with Homeostasis Model Assessment (HOMA) parameters. This cross-sectional study was conducted between March and December 2009. Any patient aged ≥ 30 years attending the medicine outpatient department of a medical university hospital in Dhaka, Bangladesh and who had a blood glucose level ordered by a physician was eligible to participate. A total of 280 participants were analysed. On fasting blood sugar results, 51% were normal, 13% had prediabetes and 36% had diabetes. Mean serum zinc level was lowest in prediabetic compared to normal and diabetic participants (mean differences were approximately 65 ppb/L and 33 ppb/L, respectively). In multiple linear regression, serum zinc level was found to be significantly lower in prediabetes than in those with normoglycemia. Beta cell function was significantly lower in prediabetes than normal participants. Adjusted linear regression for HOMA parameters did not show a statistically significant association between serum zinc level, beta cell function (P = 0.07) and insulin resistance (P = 0.08). Low serum zinc accentuated the increase in insulin resistance seen with increasing BMI. Participants with prediabetes have lower zinc levels than controls and zinc is significantly associated with beta cell function and insulin resistance. Further longitudinal population based studies are warranted and controlled trials would be valuable for establishing whether zinc supplementation in prediabetes could be a useful strategy in preventing progression to Type 2 diabetes.

Expression of membrane-bound mucins in human nasal mucosa: different patterns for MUC4 and MUC16.

PubMed

Woo, Hyun-Jae; Bae, Chang Hoon; Song, Si-Youn; Lee, Heung-Man; Kim, Yong-Dae

2010-06-01

To acquire basic information concerning the function of the membrane-bound mucin MUC16 in nasal mucosa compared with the best-characterized membrane-bound mucin, MUC4. In vitro study using semiquantatitive reverse transcription-polymerase chain reaction analysis and immunoassay. Yeungnam University College of Medicine. We examined the nasal polyps obtained during endoscopic sinus surgery in 10 patients, the normal ethmoid sinus mucosa obtained from 10 patients, and human nasal polyp epithelial (HNPE) cells. Gene expression of MUC4 and MUC16 in nasal polyps and normal nasal mucosa. In addition, we evaluated the effect of 4 physiologically relevant agents, including retinoic acid, interleukin 1beta, phorbol 12-myristate 13-acetate (PMA), and dexamethasone, on the expression of MUC4 and MUC16 in HNPE cells at the gene and protein levels. In nasal polyps, MUC4 was upregulated compared with normal nasal mucosa (P = .009), whereas MUC16 expression did not differ between nasal polyps and normal nasal mucosa. Retinoic acid and interleukin 1beta increased MUC4 expression at the gene and protein level in HNPE cells, whereas MUC16 expression was not affected. Unlike retinoic acid and interleukin 1beta, PMA and dexamethasone increased MUC16 expression, whereas they had no significant effect on MUC4 expression. Expression of MUC4 and MUC16 are regulated differently in nasal mucosa. Dexamethasone and PMA are potent mediators for the expression of MUC16 in nasal polyps.

Evaluation of risk of atherosclerosis in Indian adults.

PubMed

Pandit, Deepa; Chiplonkar, Shashi; Khadilkar, Anuradha; Kinare, Arun; Khadilkar, Vaman; Divate, Uma

2013-05-01

To investigate interrelationship of arterial measurements with metabolic syndrome (MS) components and zinc status in apparently healthy Indian adults. Anthropometry and biochemical data were recorded in 110 men and 139 women (25-50 yr). Carotid Intima media thickness (CIMT), stiffness (beta), pulse wave velocity (PWV), elasticity modulus (Ep), and arterial compliance (AC) of the right carotid artery were evaluated ultrasonically. According to definition of MS, subjects were categorized as MS-1, MS-2, MS-3. Further, normal and MS subjects were divided as zinc sufficient and deficient. In all, 12.1% subjects had 3 risk factors for MS. Mean CIMT, beta, Ep and PWV were significantly higher by 6%, 11.6%, 29.5% and 12.4% in subjects with MS than normal (p < 0.05). AC showed significant decline in MS subjects by only 3% than normal (p < 0.05). Serum zinc was inversely correlated with beta, Ep and PWV in both the genders in subjects with MS (p < 0.05). A synergistic effect of serum zinc deficiency with MS further envisages the elevated risk of arterial stiffness. Risk of atherosclerosis is marked by increase in stiffness parameters even in presence of a single MS risk and zinc deficiency may further aggravate the risk indicating need for early diagnosis.

Acceleration of Smad2 and Smad3 phosphorylation via c-Jun NH(2)-terminal kinase during human colorectal carcinogenesis.

PubMed

Yamagata, Hideo; Matsuzaki, Koichi; Mori, Shigeo; Yoshida, Katsunori; Tahashi, Yoshiya; Furukawa, Fukiko; Sekimoto, Go; Watanabe, Toshihiko; Uemura, Yoshiko; Sakaida, Noriko; Yoshioka, Kazuhiko; Kamiyama, Yasuo; Seki, Toshihito; Okazaki, Kazuichi

2005-01-01

Conversion of normal epithelial cells to tumors is associated with a shift in transforming growth factor-beta (TGF-beta) function: reduction of tumor suppressor activity and increase of oncogenic activity. However, specific mechanisms of this functional alteration during human colorectal carcinogenesis remain to be elucidated. TGF-beta signaling involves Smad2/3 phosphorylated at linker regions (pSmad2/3L) and COOH-terminal regions (pSmad2/3C). Using antibodies specific to each phosphorylation site, we herein showed that Smad2 and Smad3 were phosphorylated at COOH-terminal regions but not at linker regions in normal colorectal epithelial cells and that pSmad2/3C were located predominantly in their nuclei. However, the linker regions of Smad2 and Smad3 were phosphorylated in 31 sporadic colorectal adenocarcinomas. In particular, late-stage invasive and metastatic cancers typically showed a high degree of phosphorylation of Smad2/3L. Their extent of phosphorylation in 11 adenomas was intermediate between those in normal epithelial cells and adenocarcinomas. Whereas pSmad2L remained in the cytoplasm, pSmad3L was located exclusively in the nuclei of Ki-67-immunoreactive adenocarcinomas. In contrast, pSmad3C gradually decreased as the tumor stage progressed. Activated c-Jun NH(2)-terminal kinase in cancers could directly phosphorylate Smad2/3L. Although Mad homology 2 region sequencing in the Smad4 gene revealed a G/A substitution at codon 361 in one adenocarcinoma, the mutation did not correlate with phosphorylation. No mutations in the type II TGF-beta receptor and Smad2 genes were observed in the tumors. In conclusion, pSmad3C, which favors tumor suppressor activity of TGF-beta, was found to decrease, whereas c-Jun NH(2)-terminal kinase tended to induce the phosphorylation of Smad2/3L in human colorectal adenoma-carcinoma sequence.

Biochemical and kinetic analysis of the GH3 family beta-xylosidase from Aspergillus awamori X-100.

PubMed

Eneyskaya, Elena V; Ivanen, Dina R; Bobrov, Kirill S; Isaeva-Ivanova, Lyudmila S; Shabalin, Konstantin A; Savel'ev, Andrew N; Golubev, Alexander M; Kulminskaya, Anna A

2007-01-15

The beta-xylosidase from Aspergillus awamori X-100 belonging to the family 3 glycoside hydrolase revealed a distinctive transglycosylating ability to produce xylooligosaccharides with degree of polymerization more than 7. In order to explain this fact, the enzyme has been subjected to the detailed biochemical study. The enzymatic hydrolysis of p-nitrophenyl beta-D-xylopyranoside was found to occur with overall retention of substrate anomeric configuration suggesting cleavage of xylosidic bonds through a double-displacement mechanism. Kinetic study with aryl beta-xylopyranosides substrates, in which leaving group pK(a)s were in the range of 3.96-10.32, revealed monotonic function of log(k(cat)) and no correlation of log(k(cat)/Km) versus pKa values indicating deglycosylation as a rate-limiting step for the enzymatic hydrolysis. The classical bell-shaped pH dependence of k(cat)/Km indicated two ionizable groups in the beta-xylosidase active site with apparent pKa values of 2.2 and 6.4. The kinetic parameters of hydrolysis, Km and k(cat), of p-nitrophenyl beta-D-1,4-xylooligosaccharides were very close to those for hydrolysis of p-nitrophenyl-beta-D-xylopyranoside. Increase of p-nitrophenyl-beta-D-xylopyranoside concentration up to 80 mM led to increasing of the reaction velocity resulting in k(cat)(app)=81 s(-1). Addition of alpha-methyl D-xylopyranoside to the reaction mixture at high concentration of p-nitrophenyl-beta-D-xylopyranoside (50 mM) caused an acceleration of the beta-xylosidase-catalyzed reactions and appearance of a new transglycosylation product, alpha-methyl D-xylopyranosyl-1,4-beta-D-xylopyranoside, that was identified by 1H NMR spectroscopy. The kinetic model suggested for the enzymatic reaction was consistent with the results obtained.

Functional analysis of a proline to serine mutation in codon 453 of the thyroid hormone receptor {beta}1 gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozata, M.; Suzuki, Satoru; Takeda, Teiji

Mutations in the gene encoding human thyroid hormone receptor {beta}(hTR{beta}) have been associated with generalized resistance to thyroid hormone (GRTH). This disorder is associated with significant behavoral abnormalities. We examined the hTR{beta} gene in a family with members who manifest inappropriately normal TSH, elevated free T{sub 4}, and free and total T{sub 3}. Sequence analysis showed a cytosine to thymine transition at nucleotide 1642 in one allele of the index patient`s genomic DNA. This altered proline to serine at codon 453. The resulting mutant receptor when expressed in vitro bound DNA with high affinity, but the T{sub 3} affinity ofmore » the receptor was impaired. The mutant TR demonstrated a dominant negative effect when cotransfected with two isoforms of wild-type receptor and also in the presence of TR variant {alpha}2 in COS-1 cells. Mutations of codon 453 occur more frequently than at other sites, and four different amino acid substitutions have been reported. Significant differences in phenotype occur among affected individuals, varying from normality to moderately severe GRTH. There is no clear correlation between K{sub a} or in vitro function of the mutant receptor, and phenotype. This study extends the association between GRTH and illness, and indicates that early diagnosis and counseling are needed in families with TR{beta}1 abnormalities. 34 refs., 5 figs., 2 tabs.« less

Frequent premature ventricular contractions in an orbital spaceflight participant.

PubMed

Jennings, Richard T; Stepanek, Jan P; Scott, Luis R; Voronkov, Yury I

2010-06-01

Commercial spaceflight participants on orbital flights typically are older than career astronauts and they often have medical conditions that have not been studied at high g or in microgravity. This is a case report of a 56-yr-old orbital spaceflight participant with essential tremor and frequent premature ventricular contractions that occurred at rates up to 7000 per day. Before training and spaceflight, he was required to complete extensive clinical investigations to demonstrate normal cardiac structures and the absence of cardiac pathology. The evaluation included signal averaged ECG, transthoracic stress echocardiography, exercise tolerance tests, electrophysiological studies, cardiac MRI, electron beam CT, Holter monitoring, and overnight oximetry. While no cardiac pathology was demonstrated, the Russian medical team required that the PVCs be treated prior to training and spaceflight. For the initial flight, a selective beta-1 receptor beta blocker was used and for the second a calcium channel blocker was used in combination with a nonselective beta blocker for tremor control. Analogue environment testing assured that this combination of medications was compatible. The spaceflight participant's PVCs were incompletely suppressed with a low-dose selective beta-1 blocker, but were well suppressed by a calcium channel blocker. He tolerated in-flight periodic use of a nonselective beta blocker in combination with a calcium channel blocker. In-flight ECG and blood pressure monitoring results were normal, and an ECG obtained midmission and on landing day showed successful PVC suppression. He did not have any cardiac difficulty with launch, on-orbit operations, entry, or recovery

Self-consistent asset pricing models

NASA Astrophysics Data System (ADS)

Malevergne, Y.; Sornette, D.

2007-08-01

We discuss the foundations of factor or regression models in the light of the self-consistency condition that the market portfolio (and more generally the risk factors) is (are) constituted of the assets whose returns it is (they are) supposed to explain. As already reported in several articles, self-consistency implies correlations between the return disturbances. As a consequence, the alphas and betas of the factor model are unobservable. Self-consistency leads to renormalized betas with zero effective alphas, which are observable with standard OLS regressions. When the conditions derived from internal consistency are not met, the model is necessarily incomplete, which means that some sources of risk cannot be replicated (or hedged) by a portfolio of stocks traded on the market, even for infinite economies. Analytical derivations and numerical simulations show that, for arbitrary choices of the proxy which are different from the true market portfolio, a modified linear regression holds with a non-zero value αi at the origin between an asset i's return and the proxy's return. Self-consistency also introduces “orthogonality” and “normality” conditions linking the betas, alphas (as well as the residuals) and the weights of the proxy portfolio. Two diagnostics based on these orthogonality and normality conditions are implemented on a basket of 323 assets which have been components of the S&P500 in the period from January 1990 to February 2005. These two diagnostics show interesting departures from dynamical self-consistency starting about 2 years before the end of the Internet bubble. Assuming that the CAPM holds with the self-consistency condition, the OLS method automatically obeys the resulting orthogonality and normality conditions and therefore provides a simple way to self-consistently assess the parameters of the model by using proxy portfolios made only of the assets which are used in the CAPM regressions. Finally, the factor decomposition with the self-consistency condition derives a risk-factor decomposition in the multi-factor case which is identical to the principal component analysis (PCA), thus providing a direct link between model-driven and data-driven constructions of risk factors. This correspondence shows that PCA will therefore suffer from the same limitations as the CAPM and its multi-factor generalization, namely lack of out-of-sample explanatory power and predictability. In the multi-period context, the self-consistency conditions force the betas to be time-dependent with specific constraints.

Heart Rate Dynamics During A Treadmill Cardiopulmonary Exercise Test in Optimized Beta-Blocked Heart Failure Patients

PubMed Central

Carvalho, Vitor Oliveira; Guimarães, Guilherme Veiga; Ciolac, Emmanuel Gomes; Bocchi, Edimar Alcides

2008-01-01

BACKGROUND Calculating the maximum heart rate for age is one method to characterize the maximum effort of an individual. Although this method is commonly used, little is known about heart rate dynamics in optimized beta-blocked heart failure patients. AIM The aim of this study was to evaluate heart rate dynamics (basal, peak and % heart rate increase) in optimized beta-blocked heart failure patients compared to sedentary, normal individuals (controls) during a treadmill cardiopulmonary exercise test. METHODS Twenty-five heart failure patients (49±11 years, 76% male), with an average LVEF of 30±7%, and fourteen controls were included in the study. Patients with atrial fibrillation, a pacemaker or noncardiovascular functional limitations or whose drug therapy was not optimized were excluded. Optimization was considered to be 50 mg/day or more of carvedilol, with a basal heart rate between 50 to 60 bpm that was maintained for 3 months. RESULTS Basal heart rate was lower in heart failure patients (57±3 bpm) compared to controls (89±14 bpm; p<0.0001). Similarly, the peak heart rate (% maximum predicted for age) was lower in HF patients (65.4±11.1%) compared to controls (98.6±2.2; p<0.0001). Maximum respiratory exchange ratio did not differ between the groups (1.2±0.5 for controls and 1.15±1 for heart failure patients; p=0.42). All controls reached the maximum heart rate for their age, while no patients in the heart failure group reached the maximum. Moreover, the % increase of heart rate from rest to peak exercise between heart failure (48±9%) and control (53±8%) was not different (p=0.157). CONCLUSION No patient in the heart failure group reached the maximum heart rate for their age during a treadmill cardiopulmonary exercise test, despite the fact that the percentage increase of heart rate was similar to sedentary normal subjects. A heart rate increase in optimized beta-blocked heart failure patients during cardiopulmonary exercise test over 65% of the maximum age-adjusted value should be considered an effort near the maximum. This information may be useful in rehabilitation programs and ischemic tests, although further studies are required. PMID:18719758

[Nutritional value of daily diets prepared in several regions of the country. Part VI. Value of retinol, beta-carotene and vitamin E].

PubMed

Nadolna, I; Okolska, G; Kunachowicz, H

1992-01-01

Determinations of retinol, beta-carotene and vitamin E were carried out in daily diets of manual and mental workers with medium incomes. The diets were prepared on the basis of the analysis of the Central Statistical Office in 1986 under laboratory conditions in five regions of Poland (Warszawa, Lublin, Olsztyn, Poznań, Wrocław). It was found that these diets contained respectively: vitamin A (retinol and beta-carotene) 844 and 859 micrograms, retinol 466 and 496 micrograms, beta-carotene 2267 and 2167 micrograms and vitamin E 4.82 and 5.12 mg per day. In relation to the realization of daily recommended dietary allowances by these diets, for vitamin A were met respectively 102 and 104% and for vitamin E 58 and 61%. There were considerable differences in the content of beta-carotene and vitamin E between diets prepared in all five regions of Poland.

Beta cell function after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention

PubMed Central

Hofsø, D; Jenssen, T; Bollerslev, J; Ueland, T; Godang, K; Stumvoll, M; Sandbu, R; Røislien, J; Hjelmesæth, J

2011-01-01

Objective The effects of various weight loss strategies on pancreatic beta cell function remain unclear. We aimed to compare the effect of intensive lifestyle intervention (ILI) and Roux-en-Y gastric bypass surgery (RYGB) on beta cell function. Design One year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104). Methods One hundred and nineteen morbidly obese participants without known diabetes from the MOBIL study (mean (s.d.) age 43.6 (10.8) years, body mass index (BMI) 45.5 (5.6) kg/m2, 84 women) were allocated to RYGB (n=64) or ILI (n=55). The patients underwent repeated oral glucose tolerance tests (OGTTs) and were categorised as having either normal (NGT) or abnormal glucose tolerance (AGT). Twenty-nine normal-weight subjects with NGT (age 42.6 (8.7) years, BMI 22.6 (1.5) kg/m2, 19 women) served as controls. OGTT-based indices of beta cell function were calculated. Results One year weight reduction was 30 % (8) after RYGB and 9 % (10) after ILI (P<0.001). Disposition index (DI) increased in all treatment groups (all P<0.05), although more in the surgery groups (both P<0.001). Stimulated proinsulin-to-insulin (PI/I) ratio decreased in both surgery groups (both P<0.001), but to a greater extent in the surgery group with AGT at baseline (P<0.001). Post surgery, patients with NGT at baseline had higher DI and lower stimulated PI/I ratio than controls (both P<0.027). Conclusions Gastric bypass surgery improved beta cell function to a significantly greater extent than ILI. Supra-physiological insulin secretion and proinsulin processing may indicate excessive beta cell function after gastric bypass surgery. PMID:21078684

Joint capsule treatment with enkephalin-encoding HSV-1 recombinant vector reduces inflammatory damage and behavioural sequelae in rat CFA monoarthritis.

PubMed

Lu, Ying; McNearney, Terry A; Wilson, Steven P; Yeomans, David C; Westlund, Karin N

2008-03-01

This study assessed enkephalin expression induced by intra-articular application of recombinant, enkephalin-encoding herpes virus (HSV-1) and the impact of expression on nociceptive behaviours and synovial lining inflammation in arthritic rats. Replication-conditional HSV-1 recombinant vectors with cDNA encoding preproenkephalin (HSV-ENK), or control transgene beta-galactosidase cDNA (HSV-beta-gal; control) were injected into knee joints with complete Freund's adjuvant (CFA). Joint temperatures, circumferences and nociceptive behaviours were monitored on days 0, 7, 14 and 21 post CFA and vector treatments. Lumbar (L4-6) dorsal root ganglia (DRG) and spinal cords were immunostained for met-enkephalin (met-ENK), beta-gal, HSV-1 proteins and Fos. Joint tissues were immunostained for met-ENK, HSV-1 proteins, and inflammatory mediators Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and cyclo-oxygenase-2, or stained with haematoxylin and eosin for histopathology. Compared to exuberant synovial hypertrophy and inflammatory cell infiltration seen in arthritic rats treated with CFA only or CFA and HSV-beta-gal, the CFA- and HSV-ENK-treated arthritic rats had: (i) striking preservation of synovial membrane cytoarchitecture with minimal inflammatory cell infiltrates; (ii) significantly improved nociceptive behavioural responses to mechanical and thermal stimuli; (iii) normalized Fos staining in lumbar dorsal horn; and (iv) significantly increased met-ENK staining in ipsilateral synovial tissue, lumbar DRG and spinal cord. The HSV-1 and transgene product expression were confined to ipsilateral lumbar DRG (HSV-1, met-ENK, beta-gal). Only transgene product (met-ENK and beta-gal) was seen in lumbar spinal cord sections. Targeted delivery of enkephalin-encoding HSV-1 vector generated safe, sustained opioid-induced analgesia with protective anti-inflammatory blunting in rat inflammatory arthritis.

Effect of modified wuzi yanzong granule on patients with mild cognitive impairment from oxidative damage aspect.

PubMed

Wang, Xue-mei; Fu, Hong; Liu, Geng-xin; Zhu, Wei; Li, Li; Yang, Jin-xia

2007-12-01

To observe the effects of modified Wuzi Yanzong Granule (WYG) on memory function and the activity of serum superoxide dismutase (SOD), malondialdehyde (MDA) levels, leukocyte mitochondrial DNA (mtDNA) deletion rate and beta-amyloid protein(1-28) (A beta(1-28)) in patients with mild cognitive impairment (MCI). Thirty-six patients with MCI were selected based on the internationally recognized Petersen's criteria, and equally and randomly assigned to two groups. The treated group was treated with WYG and the control group was treated with placebo for 3 months. In addition, 20 healthy subjects were included in the study as the normal control group. Changes of memory function, SOD activity, MDA content, leukocyte mtDNA deletion rate and A beta(1-28) content were observed before and after treatment. Compared with the normal control group, the memory quotient and SOD activity in patients with MCI decreased significantly (P < 0.01), while MDA, A beta(1-28) levels and the leukocyte mtDNA deletion rate increased significantly (P < 0.01). After treatment, levels of memory quotient and serum SOD activity increased while the serum MDA level, leukocyte mtDNA deletion rate and A beta(1-28) level decreased in the treated group compared with those before treatment (P<0.01, P<0.05). Meanwhile, leukocyte mtDNA deletion rate and A beta(1-28) content in the treated group were all lower than those in the control group (P<0.05). WYG could improve memory function in patients with MCI and the therapeutic mechanism is possibly related to the increased activity of anti-oxidase, the improved free radical metabolism and the alleviation of leukocyte mtDNA oxidation damage. WYG shows clinical significance in delaying the progression of MCI.

TGF-{beta} receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian

2010-09-10

Skeletal muscle differentiation is strongly inhibited by transforming growth factor type {beta} (TGF-{beta}), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-{beta}-receptors (TGF-{beta}-Rs) during skeletal muscle differentiation. We found a decrease of TGF-{beta} signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-{beta}. No changemore » in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-{beta}-R type I (TGF-{beta}-RI) and type II (TGF-{beta}-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-{beta}-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-{beta}-RII lacking the cytoplasmic domain. The TGF-{beta}-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-{beta}-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-{beta} receptors independent of Smad proteins are essential for skeletal muscle differentiation.« less

Nonessential role of beta3 and beta5 integrin subunits for efficient clearance of cellular debris after light-induced photoreceptor degeneration.

PubMed

Joly, Sandrine; Samardzija, Marijana; Wenzel, Andreas; Thiersch, Markus; Grimm, Christian

2009-03-01

During light-induced photoreceptor degeneration, large amounts of cellular debris are formed that must be cleared from the subretinal space. The integrins alphavbeta5 and alphavbeta3 are involved in the normal physiological process of phagocytosis in the retina. This study was conducted to investigate the question of whether the lack of beta5 and/or beta3 integrin subunits might influence the course of retinal degeneration and/or clearance of photoreceptor debris induced by acute exposure to light. Wild-type, beta5(-/-) and beta3(-/-) single-knockout, and beta3(-/-)/beta5(-/-) Ccl2(-/-)/beta5(-/-) double-knockout mice were exposed to 13,000 lux of white light for 2 hours to induce severe photoreceptor degeneration. Real-time PCR and Western blot analysis were used to analyze gene and protein expression, light- and electron microscopy to judge retinal morphology, and immunofluorescence to study retinal distribution of proteins. Individual or combined deletion of beta3 and beta5 integrin subunits did not affect the pattern of photoreceptor cell loss or the clearance of photoreceptor debris in mice compared with that in wild-type mice. Invading macrophages may contribute to efficient phagocytosis. However, ablation of the MCP-1 gene did not prevent macrophage recruitment. Several chemokines in addition to MCP-1 were induced after light-induced damage that may have compensated for the deletion of MCP-1. Acute clearance of a large amount of cellular debris from the subretinal space involves invading macrophages and does not depend on beta3 and beta5 integrins.

HIGH ENERGY RATE EXTRUSION OF URANIUM

DOEpatents

Lewis, L.

1963-07-23

A method of extruding uranium at a high energy rate is described. Conditions during the extrusion are such that the temperature of the metal during extrusion reaches a point above the normal alpha to beta transition, but the metal nevertheless remains in the alpha phase in accordance with the Clausius- Clapeyron equation. Upon exiting from the die, the metal automatically enters the beta phase, after which the metal is permitted to cool. (AEC)

Prenatal diagnosis of beta-thalassaemia: experience in a developing country.

PubMed

Saxena, R; Jain, P K; Thomas, E; Verma, I C

1998-01-01

We present our experience with the amplification refractory mutation system (ARMS) for the prenatal diagnosis of beta-thalassaemia in 415 pregnancies of 360 women. Five mutations of the beta-thalassaemia gene common in Asian Indians accounted for 89.2 per cent and rare mutations for 7.2 per cent of all mutant chromosomes, while 3.3 per cent of chromosomes remained uncharacterized. Identical mutations were present in both parents in 43.2 per cent of cases, due to caste-based marriages in India. A confirmed diagnosis was given in 401 (98.3 per cent) cases, of which a complete diagnosis (whether the fetus was normal, a carrier, or homozygous) was possible in 391 (94.2 per cent) of the cases. In 15 couples, the mutation was identified in only one parent. In nine of these, the identified mutation was not present in the fetus, predicting normal/carrier status, while in five the identified mutation was present in the fetus, suggesting carrier/affected status. The abortion rate was 3.9 per cent. Pitfalls in diagnosis were failure of oligonucleotides to work, maternal contamination, and false paternity. The ARMS provides an inexpensive, robust and non-isotopic method for the prenatal diagnosis of beta-thalassaemia in India. Recommendations are outlined for establishing a prenatal diagnostic service in developing countries.

Altered expression of extracellular matrix molecules and their receptors in chronic pancreatitis and pancreatic adenocarcinoma in comparison with normal pancreas.

PubMed

Shimoyama, S; Gansauge, F; Gansauge, S; Oohara, T; Beger, H G

1995-12-01

The aim of this study was to elucidate the expression and distribution patterns of both integrins and extracellular matrix (ECM) molecules in chronic pancreatitis (CP) and pancreatic adenocarcinoma (PC) compared with normal pancreas (NP). Expression of nine alpha-subunits (alpha 2-alpha 6, alpha V, alpha L, alpha M, and alpha X), four beta-subunits (beta 1, beta 3-beta 5), and four ECM molecules (type IV collagen, laminin, fibronectin, and vitronectin) was investigated immunohistochemically. In CP, all integrins except alpha V showed nearly the same staining patterns compared with NP. Some acinar cells in CP expressed alpha V. Whereas alpha 2, alpha 3, and alpha 6 expression was stronger and diffuse, no alpha 5 expression was seen in PC. Basement membrane (BM) showed continuous staining in CP, whereas it showed discontinuous/absent staining in PC with antitype IV collagen, laminin, and vitronectin antibodies. Some carcinoma cells showed reverse correlation between alpha 2, alpha 3, and alpha 6 expression and type IV collagen and laminin expression. Fibronectin showed diffuse stromal expression in CP and PC. Some acinar cells or duct cells in CP carcinoma cells in PC showed intracellular VN expression. These results suggest that these integrins and ECM molecules are involved in inflammatory and malignant processes in pancreas.

Development of hepatocellular carcinoma in Iqgap2-deficient mice is IQGAP1 dependent.

PubMed

Schmidt, Valentina A; Chiariello, Carmine S; Capilla, Encarnación; Miller, Frederick; Bahou, Wadie F

2008-03-01

IQGAPs are multidomain scaffolding proteins that integrate Rho GTPase and Ca2+/calmodulin signals with cell adhesive and cytoskeletal reorganizational events. Targeted disruption of the murine Iqgap2 gene resulted in the age-dependent development of apoptosis and hepatocellular carcinoma (HCC), characterized by the overexpression of IQGAP1, the loss of membrane E-cadherin expression, the cytoplasmic translocation (and activation) of beta-catenin, and the overexpression of a nuclear target of beta-catenin, cyclin D1. In normal hepatocytes, IQGAP2 was found to exist as one component of a multifunctional scaffolding complex comprising IQGAP1, beta-catenin, and E-cadherin, with no evidence for direct IQGAP1-IQGAP2 interactions. Interbreeding of Iqgap2(-/-) mice into the Iqgap1(-/-) background resulted in the phenotypic correction of the preexisting hepatopathy, decreases in the incidence and sizes of HCC tumors, and the normalization of overall survival rates compared to those of Iqgap2(-/-) mice, suggesting that maximal penetrance of the Iqgap2(-/-) HCC phenotype requires the coordinate expression of IQGAP1. These results identify Iqgap2 as a novel tumor suppressor gene specifically linked to the development of HCC and the activation of the Wnt/beta-catenin signaling pathway, while also suggesting that IQGAP1 and IQGAP2 retain functionally divergent roles in hepatocellular carcinogenesis.

Quadrupole deformation ({beta},{gamma}) of light {Lambda} hypernuclei in a constrained relativistic mean field model: Shape evolution and shape polarization effect of the {Lambda} hyperon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu Bingnan; Zhao Enguang; Center of Theoretical Nuclear Physics, National Laboratory of Heavy Ion Accelerator, Lanzhou 730000

2011-07-15

The shapes of light normal nuclei and {Lambda} hypernuclei are investigated in the ({beta},{gamma}) deformation plane by using a newly developed constrained relativistic mean field (RMF) model. As examples, the results of some C, Mg, and Si nuclei are presented and discussed in details. We found that for normal nuclei the present RMF calculations and previous Skyrme-Hartree-Fock models predict similar trends of the shape evolution with the neutron number increasing. But some quantitative aspects from these two approaches, such as the depth of the minimum and the softness in the {gamma} direction, differ a lot for several nuclei. For {Lambda}more » hypernuclei, in most cases, the addition of a {Lambda} hyperon alters slightly the location of the ground state minimum toward the direction of smaller {beta} and softer {gamma} in the potential energy surface E{approx}({beta},{gamma}). There are three exceptions, namely, {sub {Lambda}}{sup 13}C, {sub {Lambda}}{sup 23}C, and {sub {Lambda}}{sup 31}Si in which the polarization effect of the additional {Lambda} is so strong that the shapes of these three hypernuclei are drastically different from their corresponding core nuclei.« less

A novel glycoside from Acanthus hirsutus (Acanthaceae).

PubMed

Capanlar, Seval; Böke, Nazli; Yaşa, Ihsan; Kirmizigül, Süheyla

2010-04-01

A novel glycoside, hirsutusoide (1), characterized as 2-(o-hydroxyphenyl)-2-hydroxyethenyl-O-beta-glucopyranoside, was isolated from the endemic Acanthus hirsutus Boiss. In addition to compound 1, three known glycosides, luteolin-7-O-beta-D-glucuronide (2), beta-sitosterol-3-O-beta-D-glucopyranoside (3) and (2R)-2-O-beta-D-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one (4), were also isolated. Compound 2 was the first report from this genus. Antimicrobial and antioxidant activity of the extracts and the novel compound were investigated by determining MIC (microg/mL) and IC50 (microg/mL) values, respectively.

An Investigation of the Neutral Cascade Muon Semileptonic Decay and its Observation at KTeV, Fermilab (in Portuguese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomes, Ricardo Avelino

2005-07-01

The authors report an investigation of the semileptonic decay Ξ 0 → Σ + μ -more » $$\\bar{v}$$ μ. This decay was observed for the first time with nine identified events using the KTeV beam line and detector at Fermilab. The decay is normalized to the Ξ 0 beta decay mode and yields a value for the ratio of decay rates Γ(Ξ 0 → Σ 0 μ -$$\\bar{v}$$ μ)/Γ(Ξ 0 → Σ +e -$$\\bar{v}$$ e) of (1.8$$+0.7\\atop{-0.5}$$(stat.) ± 0.2(syst.)) x 10 -0 at the 68.27% confidence level, being the official measurement of KTeV Collaboration. They also used the dominant decay Ξ 0 → Γπ 0(Γ → pπ -) as normalization mode in an independent analysis which corroborated with the main result. In addition, a new measurement of the Ξ 0 → Σ + e -$$\\bar{v}$$ e branching ratio is presented, based on 1139 events and normalized to the Ξ 0 → Γπ 0(Γ → pπ -) decay mode. The results are in agreement with the SU(3) flavor symmetric quark model.« less

Preliminary study of Alzheimer's Disease diagnosis based on brain electrical signals using wireless EEG

NASA Astrophysics Data System (ADS)

Handayani, N.; Akbar, Y.; Khotimah, S. N.; Haryanto, F.; Arif, I.; Taruno, W. P.

2016-03-01

This research aims to study brain's electrical signals recorded using EEG as a basis for the diagnosis of patients with Alzheimer's Disease (AD). The subjects consisted of patients with AD, and normal subjects are used as the control. Brain signals are recorded for 3 minutes in a relaxed condition and with eyes closed. The data is processed using power spectral analysis, brain mapping and chaos test to observe the level of complexity of EEG's data. The results show a shift in the power spectral in the low frequency band (delta and theta) in AD patients. The increase of delta and theta occurs in lobus frontal area and lobus parietal respectively. However, there is a decrease of alpha activity in AD patients where in the case of normal subjects with relaxed condition, brain alpha wave dominates the posterior area. This is confirmed by the results of brain mapping. While the results of chaos analysis show that the average value of MMLE is lower in AD patients than in normal subjects. The level of chaos associated with neural complexity in AD patients with lower neural complexity is due to neuronal damage caused by the beta amyloid plaques and tau protein in neurons.

Selection of suitable reference genes for normalization of genes of interest in canine soft tissue sarcomas using quantitative real-time polymerase chain reaction.

PubMed

Zornhagen, K W; Kristensen, A T; Hansen, A E; Oxboel, J; Kjaer, A

2015-12-01

Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) is a sensitive technique for quantifying gene expression. Stably expressed reference genes are necessary for normalization of RT-qPCR data. Only a few articles have been published on reference genes in canine tumours. The objective of this study was to demonstrate how to identify suitable reference genes for normalization of genes of interest in canine soft tissue sarcomas using RT-qPCR. Primer pairs for 17 potential reference genes were designed and tested in archival tumour biopsies from six dogs. The geNorm algorithm was used to analyse the most suitable reference genes. Eight potential reference genes were excluded from this final analysis because of their dissociation curves. β-Glucuronidase (GUSB) and proteasome subunit, beta type, 6 (PSMB6) were most stably expressed with an M value of 0.154 and a CV of 0.053 describing their average stability. We suggest that choice of reference genes should be based on specific testing in every new experimental set-up. © 2014 John Wiley & Sons Ltd.

Investigation of the fracture mechanism of Ti-5Al-2.5Sn at cryogenic temperatures

NASA Technical Reports Server (NTRS)

Van Stone, R. H.; Low, J. R., Jr.; Shannon, J. L., Jr.

1978-01-01

Fractography and metallographic sectioning were used to investigate the influence of microstructure on the fracture mechanism and fracture toughness (KIC) of normal interstitial and extra low interstitial (ELI) Ti-5Al-25Sn at 20 K (-423 F) and 77 K (-320 F). Plates of each grade were mill annealed at 815 C followed by either air or furnace cooling. These variations in composition and cooling rate resulted in differences in the volume fraction and internal structure of the dispersed beta phase and in the ordering of the alpha matrix. The ELI alloys were tougher than the normal interstitial plates. KIC of the furnace-cooled ELI plate was 25% lower than that of the air-cooled ELI material. Variations in cooling rate had no influence of KIC of the normal interstitial alloys. Fractography showed that a large portion of the fracture surfaces were covered with elongated dimples. Metallographic sections of specimens deformed at 77 K showed that these features form at the intersections of slip bands or deformation twins with grain or twin boundaries. Ordering and higher interstitial levels increase the local strain in slip bands resulting in void nucleation at lower macroscopic strains and lower KIC values.

Obsessive-compulsive dimension localized using low-resolution brain electromagnetic tomography (LORETA).

PubMed

Sherlin, Leslie; Congedo, Marco

2005-10-21

Electroencephalographic mapping techniques have been used to show differences between normal subjects and those diagnosed with various mental disorders. To date, there is no other research using the techniques of low-resolution brain electromagnetic tomography (LORETA) with the obsessive-compulsive disorder (OCD) population. The current investigation compares current source density measures of persons with OCD symptoms to an age-matched control group. The main finding is excess current source density in the Beta frequencies in the cingulate gyrus. This Beta activity is primarily located in the middle cingulate gyrus as well as adjacent frontal parieto-occipital regions. Lower frequency Beta is prominent more anteriorly in the cingulate gyrus whereas higher frequency Beta is seen more posteriorly. These preliminary findings indicate the utility of LORETA as a clinical and diagnostic tool.

The neurotrophins act synergistically with LIF and members of the TGF-beta superfamily to promote the survival of spiral ganglia neurons in vitro.

PubMed

Marzella, P L; Gillespie, L N; Clark, G M; Bartlett, P F; Kilpatrick, T J

1999-12-01

A number of growth factor families have been implicated in normal inner ear development, auditory neuron survival and protection. Several growth factors, including transforming growth factor-beta5 (TGF-beta5) and TGF-beta3, neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were tested for their ability, individually or in combination, to promote auditory neuron survival in dissociated cell cultures of early rat post-natal spiral ganglion cells (SGCs). The results indicate that at discrete concentrations all growth factors act in an additive fashion and some in synergy when promoting neuronal survival. These findings support the hypothesis that growth factors from different families may be interdependent when sustaining neuronal integrity.

OXIDATION YIELD IN FRICKE DOSIMETRY OF P$sup 32$ BETA RADIATION (in Portuguese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baptista, A.M.; da Silva, J.G.

1962-05-01

A determination was made of the G-value, the number of ions formed by the absorption of 100 ev of energy, in the ferrous sulfate dosimetry of P/sup 32/ beta particles. The value obtained was: G = 15.6 plus or minus 0.07. A discussion is included of the errors which may possibly affect the results. (tr- auth)

The impact of Chinese cultural values on Taiwan nursing leadership styles: comparing the self-assessments of staff nurses and head nurses.

PubMed

Chang, Yuanmay

2008-06-01

The purpose of this study was to investigate the influence of Chinese culture on nursing leadership behavior in Taiwan nurses. A descriptive study compared staff nurses' assessment of Chinese value in the leadership behavior of their head nurses. Data analysis was made on a convenience sample in Taiwan of 214 head nurses and 2,127 staff nurses who had worked with their head nurse for at least one year. Six medical centers and regional hospitals in northern (Taipei), central (Taichung) and southern (Kaohsiung) Taiwan were recruited for this study. Instruments included the demographic questionnaire, Chinese Value Survey, and Kang's Chinese Leadership Behaviors Module Scale. Results indicated that head nurses scored significantly higher than staff nurses in terms of all cultural values and leadership behaviors. Both staff nurses and head nurses scored the highest mean scores in personal integrity (Yi) and human connectedness (Ren) and the lowest in moral discipline (Li). Staff nurse perceptions of leadership behavior indicated the role of parent to be higher than either the role of director or mentor. Head nurses perceptions of leadership behavior emphasized the role of the director more than either parent or mentor. There were no significant differences between the staff nurses and head nurses in terms of expectative leadership behavior, which gave the role of director higher mean scores than those of either the parent or mentor. Positive and significant associations (r = .266 to r = .334) were found between cultural values and perceptions of leadership behavior. Cultural values predicted 10.6% of leadership behavior variance. The three demographic characteristics of location in northern Taiwan (beta = .09), intention to leave (beta = -.14), and general unit (beta = .10) and the two cultural values of human connectedness (Ren) (beta = .16) and personal integrity (Yi) (beta = .16) together reported a cumulative R2 of 14.6% to explain variance in leadership behavior perceptions. Results of this study identified the important cultural values "Ren" and "Yi". Managers and administrators could add the consideration of such cultural values into nursing leadership to enhance the organization in which Taiwan nurses work.

Molecular analysis of Hb Q-H disease and Hb Q-Hb E in a Singaporean family.

PubMed

Tan, J; Tay, J S; Wong, Y C; Kham, S K; Bte Abd Aziz, N; Teo, S H; Wong, H B

1995-01-01

Hb Q (alpha 74Asp-His) results from a mutation in the alpha-gene such that abnormal alpha Q-chains are synthesized. The alpha Q-chains combine with the normal Beta A-chains to form abnormal Hb alpha 2Q beta 2A (Hb Q). Hb Q-H disease is rare, and has been reported only in the Chinese. We report here a Chinese family, were the mother diagnosed with Hb Q-H disease and the father with Hb E heterozygosity and a child with Hb Q-E-thalassemia. Thalassemia screening of the mother's blood revealed a Hb level of 6.8g/dl with low MCV and MCH. Her blood film was indicative of thalassemia. Cellulose acetate electrophoresis showed Hb H and Hb Q with the absence of Hb A. Globin chain biosynthesis was carried out and alpha Q- and beta-chains were detected. Normal alpha- chains were absent. Digestion of the mother's DNA with Bam HI and Bgl II followed by hybridization with the 1.5 kb alpha-Pst probe showed a two alpha-gene deletion on one chromosome and the -alpha Q chain mutant with the -alpha 4.2 defect on the other chromosome. DNA amplification studies indicated the two-gene deletion to be of the -SEA/ defect. The patient was concluded to possess Hb Q-H disease (--SEA/-alpha 4.2Q). Cellulose acetate electrophoresis of the father's blood showed the presence of Hb A, F and E. Molecular analysis of the father's DNA confirmed an intact set of alpha-genes (alpha alpha/alpha alpha). Globin chain biosynthesis of fetal blood of their child showed gamma, beta A, beta E, alpha A and alpha Q-chains. Molecular analysis of the child's DNA showed one alpha-gene deletion, thus giving a genotype of alpha alpha/-alpha 4.2Q beta beta E.

Plasma beta-endorphin, beta-lipotropin and corticotropin in polycystic ovarian disease.

PubMed

Laatikainen, T; Salminen, K; Virtanen, T; Apter, D

1987-04-01

In 9 women with polycystic ovarian disease (PCOD) and in 11 control subjects at the follicular phase of the normal cycle, blood samples were collected at 15-min intervals during a 2 h period of bed rest for the assay of beta-endorphin, beta-lipotropin, corticotropin, cortisol and prolactin. During the study period, the plasma levels of these hormones decreased more significantly in the PCOD than in the control group, suggesting that the PCOD patients had a more significant stress response to the puncture of the vein than the control subjects. The second hour of the study period was considered to represent resting levels of hormones. The mean resting levels (+/- S.E.) of the hormones between the PCOD and control groups, respectively, were as follows: beta-E, 2.0 +/- 0.4 vs. 1.1 +/- 0.1 pmol/l, p less than 0.05; beta-LPH, 3.4 +/- 0.6 vs. 2.1 +/- 0.5 pmol/l, N.S.; corticotropin, 2.0 +/- 0.3 vs. 1.1 +/- 0.5 pmol/l, p less than 0.05; cortisol, 176 +/- 24 vs. 128 +/- 16, N.S.; and prolactin; 3.9 +/- 0.6 vs. 5.6 +/- 1.2 ng/ml, N.S. These results confirm the previous findings on increased circulating levels of beta-E in PCOD. A concomitant increase of the plasma level of corticotropin suggests that the basal secretion of both beta-E and corticotropin from the anterior pituitary gland is increased in women with PCOD.

V(D)J recombination and allelic exclusion of a TCR beta-chain minilocus occurs in the absence of a functional promoter.

PubMed

Alvarez, J D; Anderson, S J; Loh, D Y

1995-08-01

Transcriptional activation of rearranging Ag receptor gene segments has been hypothesized to regulate their accessibility to V(D)J recombination. We analyzed the role of a functional promoter in the rearrangement of the murine TCR beta-chain locus using two transgenic minilocus constructs. These miniloci each contain an unrearranged V beta 8.3 gene. One has a wild-type V beta 8.3 gene, but the other has a V beta 8.3 gene with a promoter mutation that was previously shown to abrogate transcription in tissue culture. FACS analysis of thymus and lymph node cells from transgenic mouse lines showed that only the lines with the wild-type V beta 8.3 gene promoter express an 8.3 TCR beta-chain. Consistent with the protein expression data, V beta 8.3 gene transcripts were found only in the transgenic lines with the wild-type promoter. Using a quantitative PCR-based assay, it was shown that both types of transgenic lines recombine the V beta 8.3 gene at similar levels. Rearrangement of the transgenes was normal with respect to thymic development and junctional reading frame. Interestingly, both types of miniloci also underwent allelic exclusion in that recombination was blocked by the expression of a rearranged TCR beta-chain transgene. We conclude that a functional V beta gene promoter is not necessary for proper V(D)J recombination to occur.

A recombinant tail-less integrin beta 4 subunit disrupts hemidesmosomes, but does not suppress alpha 6 beta 4-mediated cell adhesion to laminins

PubMed Central

1995-01-01

To examine the function of the alpha 6 beta 4 integrin we have determined its ligand-binding ability and overexpressed two potentially dominant negative mutant beta 4 subunits, lacking either the cytoplasmic or extracellular domain, in bladder epithelial 804G cells. The results of cell adhesion and radioligand-binding assays showed that alpha 6 beta 4 is a receptor for several laminin isoforms, including laminin 1, 2, 4, and 5. Overexpression of the tail-less or head-less mutant beta 4 subunit did not suppress alpha 6 beta 4-mediated adhesion to laminins, as both types of transfectants adhered to these ligands in the presence of blocking anti-beta 1 antibodies as well as the controls. However, immunofluorescence experiments indicated that the endogenous alpha 6 beta 4 integrin and other hemidesmosomal markers were not concentrated in hemidesmosomes in cells overexpressing tail- less beta 4, while the distribution of these molecules was not altered in cells overexpressing the head-less subunit. Electron microscopic studies confirmed that cells overexpressing tail-less beta 4 had a drastically reduced number of hemidesmosomes, while cells expressing the head-less subunit had a normal number of these structures. Thus, expression of a tail-less, but not a head-less mutant beta 4 subunit leads to a dominant negative effect on hemidesmosome assembly without suppressing initial adhesion to laminins. We conclude that the alpha 6 beta 4 integrin binds to several laminins and plays an essential role in the assembly and/or stability of hemidesmosomes, that alpha 6 beta 4- mediated adhesion and hemidesmosome assembly have distinct requirements, and that it is possible to use a dominant negative approach to selectively interfere with a specific function of an integrin. PMID:7721947

Expression of a mutation causing hypertrophic cardiomyopathy disrupts sarcomere assembly in adult feline cardiac myocytes.

PubMed

Marian, A J; Yu, Q T; Mann, D L; Graham, F L; Roberts, R

1995-07-01

Mutations in the beta-myosin heavy chain (beta MyHC) induce hypertrophic cardiomyopathy (HCM), cardiac hypertrophy, and sarcomere disarray, with the latter being the characteristic hallmark. Thus, we sought to determine whether expression of mutant beta MyHC in adult feline cardiac myocytes, a species known to develop HCM with a phenotype identical to that in humans, induces sarcomere disarray. A full-length beta MyHC cDNA was cloned from a human heart cDNA library, and an HCM-causing mutation (Arg403Gln) was induced in the beta MyHC cDNA by site-directed mutagenesis using polymerase chain reaction (PCR). The normal and mutant beta MyHC cDNAs were cloned into p delta E1spIB shuttle vector, downstream from a cytomegalovirus (CMV) promoter. Replication-deficient recombinant adenoviral constructs (Ad5/CMV/beta MyHC-N and Ad5/CMV/beta MyHC-403) were generated through homologous recombination of p delta E1spIB/CMV/beta MyHC-N or Ad5/CMV/beta MyHC-403 and pBHG10 after cotransfection in 293 host cells. Infection of COS-1 cells with the beta MyHC construct resulted in the expression of a full-length myosin protein. Efficiency of infection of isolated adult cardiac myocytes was > 95%. Expression of the beta MyHC constructs into mRNA at 48 hours after infection of feline cardiac myocytes was confirmed by reverse transcription-PCR. The net total protein and beta-myosin synthesis were determined by using the amount of incorporation of [3H]phenylalanine into total protein and beta-myosin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A simple approach for assessing equilibrated Kt/V beta 2-M on a routine basis.

PubMed

Casino, Francesco G; Pedrini, Luciano A; Santoro, Antonio; Mandolfo, Salvatore; David, Salvatore; De Cristofaro, Vincenzo; Teatini, Ugo; Lomonte, Carlo; Lopez, Teodoro

2010-09-01

Large observational studies have shown a reduction in morbidity and mortality in patients on high-flux haemodialysis (HD) or convective techniques, compared with low-flux HD. An index to evaluate treatment efficiency in middle molecule (MM) removal would be recommended. Since beta-2-microglobulin (beta2-M) is a recognized MM marker, we evaluated an easy approach for Kt/V(beta2-M) assessment on a routine basis, avoiding other complex methods. An equation that estimates single-pool (sp) Kt/V(beta2-M) was derived from Leypoldt's formula, which calculates beta2-M dialyser clearance (K(beta2-M)) from the post/pre-dialysis beta2-M concentration (C(t)/C(0)) ratio and the weight loss/end-dialysis weight (Delta W/W) ratio. Our equation, spKt/V(beta2-M) = 6.12 Delta W/W [1 - ln(C(t)/C(0))/ln(1 + 6.12 Delta W/W)], was derived by assuming urea distribution volume (V(u)) as 49% of W and beta2-M volume (V(beta2-M)) as V(u)/3, in agreement with the average patient values in the HEMO Study. The spKt/V(beta2-M) values calculated with our equation (F) in 129 patients on 407 sessions of different high-flux treatments were compared with those calculated with the method applied in the HEMO Study (HM). Equilibrated beta2-M concentration (C(eq)) of the same sessions was also estimated with the equation for C(eq) by Tattersall, and equilibrated Kt/V (eKt/V(beta2-M)) was calculated by introducing Tattersall's equation into our simplified spKt/V(beta2-M) formula. Mean results of our spKt/V(beta2-M) equation (F) were very close to those of the HM method (1.48 +/- 0.38 vs 1.47 +/- 0.37). The difference was less than +/-0.1 in 95% of cases. A mean end-session beta2-M rebound of 44 +/- 14% was predicted, which caused a mean reduction in actual Kt/V(beta2-M) of ~27% (eKt/V(beta2-M) = 1.08 +/- 0.26). The method proposed to estimate spKt/V(beta2-M) and eKt/V(beta2-M) could become a simple tool to monitor the efficiency of high-flux HD and convective techniques and to evaluate the adequacy of treatments in terms of MM removal. Moreover, it might help to better understand the effects of different dialysis schedules. Validation on a larger dialysis population is required.

[The disease of beta 2-amyloid deposition in the differential diagnosis of juxta-articular subchondral geode lesions].

PubMed

Marri, C; Romagnoli, C; Solano, G; Caldeo, A; Emiliani, G

1993-01-01

Beta-2 amyloidosis deposition is a new type of amyloidosis recently observed in long-term hemodialysis patients. One of the major osteoarticular complications of this disease is the appearance of subchondral bone cysts. In this paper the radiologic features of such radiolucencies are described and the criteria are outlined of the differential diagnosis from the geodes found in other arthropathies or para-physiologic conditions. The importance of the status of the joint space is stressed: on the basis of its patterns, arthropathies may be grouped as follows: inhomogeneous space narrowing in degenerative arthritis; homogeneous space narrowing in inflammatory arthritis; normal or nearly normal joint space if there is no/not-prevalent involvement of articular cartilage.

Biological effects of radiation, metabolic and replication kinetics alterations

NASA Technical Reports Server (NTRS)

Post, J.

1972-01-01

The biological effects of radiation upon normal and cancerous tissues were studied. A macromolecular precursor of DNA, 3ETdR, was incorporated into the cell nucleus during synthesis and provided intranuclear beta radiation. Tritium labeled cells were studied with autoradiographic methods; cell cycle kinetics were determined and cell functions modified by radiation dosage or by drugs were also evaluated. The long term program has included; (1) effects of radiation on cell replication and the correlation with incorporated dose levels, (2) radiation induced changes in cell function, viz., the response of beta irradiated spleen lymphocytes to antigenic stimulation by sheep red blood cells (SRBC), (3) kinetics of tumor and normal cell replication; and (4) megakaryocyte formation and modification by radiomimetic drugs.

Superallowed Beta Decay Studies at TRIUMF --- Nuclear Structure and Fundamental Symmetries

NASA Astrophysics Data System (ADS)

Zganjar, E. F.; Achtzehn, T.; Albers, D.; Andreoiu, C.; Andreyev, A. N.; Austin, R. A. E.; Ball, G. C.; Behr, J. A.; Biosvert, G. C.; Bricault, P.; Bishop, S.; Chakrawarthy, R. S.; Churchman, R.; Cross, D.; Cunningham, E.; D'Auria, J. M.; Dombsky, M.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hackman, G.; Hanemaayer, V.; Hardy, J. C.; Hodgson, D. F.; Hyland, B.; Iacob, V.; Klages, P.; Koopmans, K. A.; Kulp, W. D.; Lassen, J.; Lavoie, J. P.; Leslie, J. R.; Linder, T.; MacDonald, J. A.; Mak, H.-B.; Melconian, D.; Morton, A. C.; Ormand, W. E.; Osborne, C. J.; Pearson, C. J.; Pearson, M. R.; Phillips, A. A.; Piechaczek, A.; Ressler, J.; Sarazin, F.; Savard, G.; Schumaker, M. A.; Scraggs, H. C.; Svensson, C. E.; Valiente-Dobon, J. J.; Towner, I. S.; Waddington, J. C.; Walker, P. M.; Wendt, K.; Wood, J. L.

2007-04-01

Precision measurement of the beta -decay half-life, Q-value, and branching ratio between nuclear analog states of Jpi = 0+ and T=1 can provide critical and fundamental tests of the Standard Model's description of electroweak interactions. A program has been initiated at TRIUMF-ISAC to measure the ft values of these superallowed beta transitions. Two Tz = 0, A > 60 cases, 74Rb and 62Ga, are presented. These are particularly relevant because they can provide critical tests of the calculated nuclear structure and isospin-symmetry breaking corrections that are predicted to be larger for heavier nuclei, and because they demonstrate the advance in the experimental precision on ft at TRIUMF-ISAC from 0.26% for 74Rb in 2002 to 0.05% for 62Ga in 2006. The high precision world data on experimental ft and corrected Ft values are discussed and shown to be consistent with CVC at the 10-4 level, yielding an average Ft = 3073.70(74) s. This Ft leads to Vud = 0.9737(4) for the up-down element of the Standard Model's CKM matrix. With this value and the Particle Data Group's 2006 values for Vus and Vub, the unitarity condition for the CKM matrix is met. Additional measurements and calculations are needed, however, to reduce the uncertainties in that evaluation. That objective is the focus of the continuing program on superallowed-beta decay at TRIUMF-ISAC.

Multichannel linear descriptors analysis for event-related EEG of vascular dementia patients during visual detection task.

PubMed

Lou, Wutao; Xu, Jin; Sheng, Hengsong; Zhao, Songzhen

2011-11-01

Multichannel EEG recorded in a task condition could contain more information about cognition. However, that has not been widely investigated in the vascular-dementia (VaD)- related studies. The purpose of this study was to explore the differences of brain functional states between VaD patients and normal controls while performing a detection task. Three multichannel linear descriptors, i.e. spatial complexity (Ω), field strength (Σ) and frequency of field changes (Φ), were applied to analyse four frequency bands (delta, theta, alpha and beta) of multichannel event-related EEG signals for 12 VaD patients (mean age ± SD: 69.25 ± 10.56 years ; MMSE score ± SD: 22.58 ± 4.42) and 12 age-matched healthy subjects (mean age ± SD: 67.17 ± 5.97 years ; MMSE score ± SD: 29.08 ± 0.9). The correlations between the three measures and MMSE scores were also analysed. VaD patients showed a significant higher Ω value in the delta (p = 0.013) and theta (p = 0.021) frequency bands, a lower Σ value (p = 0.011) and a higher Φ (p = 0.008) value in the delta frequency band compared with normal controls. The MMSE scores were negatively correlated with the Ω (r = -0.52, p = 0.01) and Φ (r = -0.47, p = 0.02) values in the delta frequency band. The results indicated the VaD patients presented a reduction of synchronization in the slow frequency band during target detection, and suggested more neurons might be activated in VaD patients compared with normal controls. The Ω and Φ measures in the delta frequency band might be used to evaluate the degree of cognitive dysfunction. The multichannel linear descriptors are promising measures to reveal the differences in brain functions between VaD patients and normal subjects, and could potentially be used to evaluate the degree of cognitive dysfunction in VaD patients. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Behaviour of beta 2-adrenoceptors on lymphocytes under continuous and pulsatile tocolysis with Fenoterol.

PubMed

Schmidt-Rhode, Peter; Brunke, Björn; Schröer, Heinrich; Obert, Kirstin; Schlegel, Kerstin; Sturm, Gerhard; Schulz, Klaus-Dieter; von Wichert, Peter

2003-01-01

The present study investigates the population of beta 2-receptors on lymphocytes in pregnant women with premature labor between the 29th and 34th week of pregnancy. The population of receptors on lymphocytes correlates with that on the myometrium, which is not accessible for study during pregnancy. Fourteen patients received a pulsatile tocolysis, while ten women received a continuous tocolysis with Fenoterol. Assuming an equal population of receptors in both groups before commencement of therapy, the numbers of receptors in the patients with continuous tocolysis fell to about 35% of the initial value after 72 hours. Under pulsatile tocolysis, the numbers of receptors remained unchanged for a period of three days and was still only just below 70% of the initial value by the seventh day. Our data demonstrate that continuous administration of the short-acting beta 2-agonist Fenoterol resulted in a substantial loss of beta 2-adrenoceptors on lymphocytes. In contrast, intermittent administration of the same beta 2-adrenergic agonist prevented the onset of receptor down-regulation in pregnant women with preterm labor. Further studies are required to investigate the impact of the decreased loss of beta 2-adrenoceptor density on the good clinical experience with intermittent tocolysis.

Comprehensive authentication of (E)-alpha(beta)-ionone from raspberries, using constant flow MDGC-C/P-IRMS and enantio-MDGC-MS.

PubMed

Sewenig, Sabine; Bullinger, Dino; Hener, Uwe; Mosandl, Armin

2005-02-23

A new coupling system of GC-GC, connected via a Multi Column Switching Device MCS2 for measuring isotope ratios, is introduced. By means of several standard substances the precise and accurate measurement of isotopic values is proved. First applications concerning the authentication of raspberry aroma compounds are established. Consequently, the combination of constant flow multidimensional gas chromatography-combustion/pyrolysis-isotope ratio mass spectrometry (MDGC-C/P-IRMS) is applied to the authenticity assessment of (E)-alpha(beta)-ionone from six different raspberry cultivars. Furthermore, 12 commercially available raspberry products and samples of (E)-alpha(beta)-ionone, some declared to be natural, are investigated. delta(2)Eta(V)(-)(SMOW) and delta(13)C(V)(-)(PDB) values of (E)-alpha(beta)-ionone are determined, and characteristic authenticity ranges were concluded from raspberries by correlation of both delta(2)Eta(V)(-)(SMOW) and delta(13)C( V)(-)(PDB) values. The results are correlated with the determination of enantiomeric purities of (E)-alpha-ionone, using stir bar sorptive extraction enantio-multidimensional gas chromatography mass spectrometry (SBSE-enantio-MDGC-MS).

Purification and properties of beta-galactosidase from Aspergillus nidulans.

PubMed

Díaz, M; Pedregosa, A M; de Lucas, J R; Torralba, S; Monistrol, I F; Laborda, F

1996-12-01

Beta-Galactosidase from mycelial extract of Aspergillus nidulans has been purified by substrate affinity chromatography and used to obtain anti-beta-galactosidase polyclonal antibodies. A. nidulans growing in lactose as carbon source synthesizes one active form of beta-galactosidase which seems to be a multimeric enzyme of 450 kDa composed of monomers with 120 and 97 kDa. Although the enzyme was not released to the culture medium, some enzymatic activity was detected in a cell-wall extract, thus suggesting that it can be an extracellular enzyme. Beta-Galactosidase of A. nidulans is a very unstable enzyme with an optimum pH value of 7.5 and an optimum temperature of 30 degrees C. It was only active against beta-galactoside substrates like lactose and p-nitrophenyl-beta-D-galactoside (PNPG).

Amyloid-beta-sheet formation at the air-water interface.

PubMed Central

Schladitz, C; Vieira, E P; Hermel, H; Möhwald, H

1999-01-01

An amyloid(1-40) solution rich in coil, turn, and alpha-helix, but poor in beta-sheet, develops monolayers with a high beta-sheet content when spread at the air-water interface. These monolayers are resistant to repeated compression-dilatation cycles and interaction with trifluoroethanol. The secondary structure motifs were detected by circular dichroism (CD) in solution and with infrared reflection-absorption spectroscopy (IRRAS) at the interface. Hydrophobic influences are discussed for the structure conversion in an effort to understand the completely unknown reason for the natural change of the normal prion protein cellular (PrP(C)) into the abnormal prion protein scrapie (PrP(Sc)). PMID:10585952

The effect of microstructure on the fracture toughness of titanium alloys

NASA Technical Reports Server (NTRS)

Vanstone, R. H.; Low, J. R., Jr.; Shannon, J. L., Jr.

1974-01-01

The microstructure of the alpha titanium alloy Ti-5Al-2.5Sn and the metastable beta titanium alloy Beta 3 was examined. The material was from normal and extra low interstitial grade plates which were either air-cooled or furnace-cooled from an annealing treatment. Beta 3 was studied in alpha-aged and omega-aged plates which were heat treated to similar strength levels. Tensile and plane strain fracture toughness tests were conducted at room temperature on the alpha-aged material. The microstructure and fracture mechanisms of alloys were studied using optical metallography, electron microscopy, microprobe analyses, and texture pole figures. Future experiments are described.

Myopia prevention and therapy. The role of pharmaceutical agents. Japanese studies.

PubMed

Hosaka, A

1988-01-01

In order to normalize the condition of pseudomyopia, the following can be summarized: One percent cyclopentolate was effective in 63%, and 0.4% tropicamide was effective in 59% of the cases. With a value of 68% after labetalol eye drops there were no significant differences in efficacy between this drug and the above cycloplegics. In subjects treated only with placebo, 4 out of 16 eyes, i.e. 25% were relieved. A significant difference (P less than 0.01) was found between the results with the above 3 drugs and placebo. On the other hand, the efficacy of 0.25% timolol (effect in 28%) and chemical X (effect in 37%) were not significantly different from the effect of placebo, though the results with chemical X encourage further trials. It can be postulated that by releasing an abnormal tension cycloplegics reduce the myopic condition. Regarding the hypotensive action of beta-adrenergic blockers on intraocular pressure, it presumably depends mainly on inhibition of secretion in the ciliary body. The fact that labetalol appeared effective, and timolol not, in treatment trials of slight myopia might imply that the mechanism behind an effect of labetalol on slight myopia is not merely a beta-adrenergic blocking action.

Criticality in charge-asymmetric hard-sphere ionic fluids.

PubMed

Aqua, Jean-Noël; Banerjee, Shubho; Fisher, Michael E

2005-10-01

Phase separation and criticality are analyzed in z:1 charge-asymmetric ionic fluids of equisized hard spheres by generalizing the Debye-Hückel approach combined with ionic association, cluster solvation by charged ions, and hard-core interactions, following lines developed by Fisher and Levin for the 1:1 case (i.e., the restricted primitive model). Explicit analytical calculations for 2:1 and 3:1 systems account for ionic association into dimers, trimers, and tetramers and subsequent multipolar cluster solvation. The reduced critical temperatures, Tc* (normalized by z), decrease with charge asymmetry, while the critical densities increase rapidly with . The results compare favorably with simulations and represent a distinct improvement over all current theories such as the mean spherical approximation, symmetric Poisson-Boltzmann theory, etc. For z not equal to 1, the interphase Galvani (or absolute electrostatic) potential difference, Deltaphi(T), between coexisting liquid and vapor phases is calculated and found to vanish as absolute value (T-Tc) beta when T-->Tc-with, since our approximations are classical, beta = (1/2). Above Tc, the compressibility maxima and so-called k-inflection loci (which aid the fast and accurate determination of the critical parameters) are found to exhibit a strong z dependence.

Intraoperative anaphylaxis: verba volant, scripta manent!

PubMed

Bilò, M B; Cinti, B; Chiarello, M; Bonifazi, F; Moneret-Vautrin, D A

2005-11-01

We describe a case of intraoperative gelatine-induced anaphylaxis whose diagnosis was delayed as the use of gelatine during surgical procedures was omitted for two times in patient's medical records. The subject is a 66-year old woman, with a negative medical history of atopy, food and drug allergy, with arterial hypertension on a course of beta-blockers and with bladder carcinoma requiring surgery. The patient had tolerated both general and local anaesthesia on several previous occasions. On the first occasion she experienced arterial fibrillation secondary to a severe episode of hypotension following local anaesthesia, while on a course of beta-blockers. On the second occasion she developed a very severe episode of hypotension followed by the outbreak of a generalised rash during general anaesthesia. The tryptase sera level was 109 mg/L one hour after the reaction had subsided, while the basal values were normal. On the third occasion the patient redeveloped severe hypotension and a generalised rash during general anaesthesia. The allergological work-up was negative, except for intradermal test with gelatine. A study of the intra-cellular cytokines in blood lymphocytes showed a production of IL4 from CD4+ lymphocytes after stimulation by gelatine. The patient underwent a successive surgical procedure without any adverse event.

Over, and Underexpression of Endothelin 1 and TGF-Beta Family Ligands and Receptors in Lung Tissue of Broilers with Pulmonary Hypertension

PubMed Central

Dominguez-Avila, Norma; Ruiz-Castañeda, Gabriel; González-Ramírez, Javier; Fernandez-Jaramillo, Nora; Escoto, Jorge; Sánchez-Muñoz, Fausto; Marquez-Velasco, Ricardo; Bojalil, Rafael; Espinosa-Cervantes, Román; Sánchez, Fausto

2013-01-01

Transforming growth factor beta (TGFβ) is a family of genes that play a key role in mediating tissue remodeling in various forms of acute and chronic lung disease. In order to assess their role on pulmonary hypertension in broilers, we determined mRNA expression of genes of the TGFβ family and endothelin 1 in lung samples from 4-week-old chickens raised either under normal or cold temperature conditions. Both in control and cold-treated groups of broilers, endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher than levels from healthy birds (P < 0.05), whereas levels in animals with cardiac failure were intermediate. Conversely, TGFβ2 and TGFβ3 gene expression in lungs were higher in healthy animals than in ascitic animals in both groups (P < 0.05). TGFβ1, TβRI, and TβRII mRNA gene expression among healthy, ascitic, and chickens with cardiac failure showed no differences (P > 0.05). BAMBI mRNA gene expression was lowest in birds with ascites only in the control group as compared with the values from healthy birds (P < 0.05). PMID:24286074

Beta blocker effects on plasma homocysteine levels in patients with hypertension.

PubMed

Atar, Ilyas; Korkmaz, Mehmet Emin; Demircan, Senol; Atar, Inci Asli; Bozbaş, Hüseyin; Aydinalp, Alp; Ozin, Bülent; Yildirir, Aylin; Müderrisoğlu, Haldun

2005-08-01

Recent studies have shown that hyperhomocysteinemia might play a role in the pathogenesis of hypertension. The effects of antihypertensive agents on plasma homocysteine levels have not been tested extensively. We investigated the effects of beta-blocker therapy on homocysteine levels in patients with hypertension. In the study, 120 patients with newly diagnosed hypertension were enrolled. All patients received metoprolol succinate 100 mg/day initially. If blood pressure was above normal on the 15th day of follow-up, the metoprolol dosage was doubled. Before initiation of the antihypertensive medication and after the fourth month of treatment, homocysteine levels were measured. Of the 120 patients enrolled, 39 could not complete the study. Homocysteine levels decreased significantly by the end of the fourth month when compared with basal values (13.5+/-4.5 micromol/l versus 12.4+/-4.9 micromol/l; P = 0.001). There was no relation between homocysteine level and blood pressure control. There was a significant decrease in homocysteine levels in the women treated in this study (P = 0.001); however, this effect was absent in men (P = 0.185). We demonstrate that metoprolol succinate treatment significantly decreases plasma homocysteine levels in patients with hypertension, especially in women.

Escape driven by alpha-stable white noises.

PubMed

Dybiec, B; Gudowska-Nowak, E; Hänggi, P

2007-02-01

We explore the archetype problem of an escape dynamics occurring in a symmetric double well potential when the Brownian particle is driven by white Lévy noise in a dynamical regime where inertial effects can safely be neglected. The behavior of escaping trajectories from one well to another is investigated by pointing to the special character that underpins the noise-induced discontinuity which is caused by the generalized Brownian paths that jump beyond the barrier location without actually hitting it. This fact implies that the boundary conditions for the mean first passage time (MFPT) are no longer determined by the well-known local boundary conditions that characterize the case with normal diffusion. By numerically implementing properly the set up boundary conditions, we investigate the survival probability and the average escape time as a function of the corresponding Lévy white noise parameters. Depending on the value of the skewness beta of the Lévy noise, the escape can either become enhanced or suppressed: a negative asymmetry parameter beta typically yields a decrease for the escape rate while the rate itself depicts a non-monotonic behavior as a function of the stability index alpha that characterizes the jump length distribution of Lévy noise, exhibiting a marked discontinuity at alpha=1. We find that the typical factor of 2 that characterizes for normal diffusion the ratio between the MFPT for well-bottom-to-well-bottom and well-bottom-to-barrier-top no longer holds true. For sufficiently high barriers the survival probabilities assume an exponential behavior versus time. Distinct non-exponential deviations occur, however, for low barrier heights.

Systemic and lung protein changes in sarcoidosis. Lymphocyte counts, gallium uptake values, and serum angiotensin-converting enzyme levels may reflect different aspects of disease activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Check, I.J.; Kidd, M.R.; Staton, G.W. Jr.

1986-01-01

BAL lymphocyte percentages, quantitated gallium-67 lung uptake, and SACE levels have all been proposed as measures of disease activity in sarcoidosis. We analyzed 32 paired sera and BAL fluids from sarcoidosis patients by high-resolution agarose electrophoresis to look for protein changes characteristic of systemic or local inflammation and compared the results with those from the above tests. Nine patients (group 1) had serum inflammatory protein changes and increased total protein, albumin, beta 1-globulin (transferrin), and gamma-globulin levels in fluid recovered by BAL. Thirteen patients (group 2) had normal protein levels in sera but abnormal protein levels in BAL specimens. Tenmore » patients (group 3) had normal protein levels in sera and in BAL specimens. Patients in groups 1 and 2 had a disproportionate increase in beta 1-globulin (transferrin) and gamma-globulin levels in their BAL specimens. The BAL lymphocyte percentage changes paralleled the BAL protein level changes, suggesting relationships among the immunoregulatory role of these cells, increased local immunoglobulin synthesis, and the pathogenesis of altered alveolar permeability. Gallium-67 uptake was highest in patients with serum inflammatory protein changes. Thus, systemic inflammation may facilitate pulmonary gallium-67 uptake, possibly by changes in BAL fluid or serum transferrin saturation and/or kinetics. SACE levels showed no relationship to changes in the levels of serum or BAL proteins. These data suggest that the various proposed measures of disease activity reflect different aspects of inflammation in sarcoidosis.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

Oak Ridge Associated Universities (ORAU), under the Oak Ridge Institute for Science and Education (ORISE) contract, collected split surface water samples with Nuclear Fuel Services (NFS) representatives on June 12, 2013. Representatives from the U.S. Nuclear Regulatory Commission (NRC) and the Tennessee Department of Environment and Conservation were also in attendance. Samples were collected at four surface water stations, as required in the approved Request for Technical Assistance number 11-018. These stations included Nolichucky River upstream (NRU), Nolichucky River downstream (NRD), Martin Creek upstream (MCU), and Martin Creek downstream (MCD). Both ORAU and NFS performed gross alpha and gross betamore » analyses, and Table 1 presents the comparison of results using the duplicate error ratio (DER), also known as the normalized absolute difference. A DER ≤ 3 indicates at a 99% confidence interval that split sample results do not differ significantly when compared to their respective one standard deviation (sigma) uncertainty (ANSI N42.22). The NFS split sample report specifies 95% confidence level of reported uncertainties (NFS 2013). Therefore, standard two sigma reporting values were divided by 1.96. In conclusion, most DER values were less than 3 and results are consistent with low (e.g., background) concentrations. The gross beta result for sample 5198W0014 was the exception. The ORAU gross beta result of 6.30 ± 0.65 pCi/L from location NRD is well above NFS's non-detected result of 1.56 ± 0.59 pCi/L. NFS's data package includes no detected result for any radionuclide at location NRD. At NRC's request, ORAU performed gamma spectroscopic analysis of sample 5198W0014 to identify analytes contributing to the relatively elevated gross beta results. This analysis identified detected amounts of naturally-occurring constituents, most notably Ac-228 from the thorium decay series, and does not suggest the presence of site-related contamination.« less

Expression of class III beta tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome.

PubMed

Ferrandina, Gabriella; Martinelli, Enrica; Zannoni, Gian Franco; Distefano, Mariagrazia; Paglia, Amelia; Ferlini, Cristiano; Scambia, Giovanni

2007-02-01

Alterations of the beta subunit of tubulin have been reported to be predictive of resistance to radiation and antitubulin agents in several solid tumors. The aim of the study was to investigate the clinical role of beta III tubulin expression as prognostic factor for survival and as a predictive parameter of response to preoperative radiochemotherapy in a single institutional series of locally advanced cervical cancer (LACC) patients. The study included 98 LACC patients admitted to the Gynecologic Oncology Unit, Catholic University of Rome and Campobasso between January 1998 and January 2005. Immunohistochemistry was performed by using the polyclonal rabbit anti-beta III tubulin antibody (Covance, Princeton, NJ, USA). The value of 10% immunostained tumor cells was arbitrarily chosen as cut-off value to distinguish cases with high versus low beta III tubulin content. In the whole series, beta III tubulin immunoreaction was detectable in 66/98 cases (67.3%), and the percentage of positively stained cells ranged from 0 to 100% (median=10%). The percentages of cases with high beta III tubulin expression were shown not to be differently distributed according to clinico-pathological characteristics. There was no statistically significant difference in the distribution of cases with high beta III tubulin expression according to clinical and pathological response to treatment. During the follow-up period, recurrence and death of disease occurred in 15 and 13 cases, respectively. There was no difference in disease-free and overall survival in cases with high versus low beta III tubulin expression. The assessment of class III beta tubulin status seems of little usefulness in order to identify LACC patients with poor chance of response to concomitant radiochemotherapy and unfavorable prognosis.

Beta oscillatory responses in healthy subjects and subjects with mild cognitive impairment☆

PubMed Central

Güntekin, Bahar; Emek-Savaş, Derya Durusu; Kurt, Pınar; Yener, Görsev Gülmen; Başar, Erol

2013-01-01

The aim of the present study was to investigate the role of beta oscillatory responses upon cognitive load in healthy subjects and in subjects with mild cognitive impairment (MCI). The role of beta oscillations upon cognitive stimulation is least studied in comparison to other frequency bands. The study included 17 consecutive patients with MCI (mean age = 70.8 ± 5.6 years) according to Petersen's criteria, and 17 age- and education-matched normal elderly controls (mean age = 68.5 ± 5.5 years). The experiments used a visual oddball paradigm. EEG was recorded at 30 cortical locations. EEG-evoked power, inter-trial phase synchronization, and event-related beta responses filtered in 15–20 Hz were obtained in response to target and non-target stimuli for both groups of subjects. In healthy subjects, EEG-evoked beta power, inter-trial phase synchronization of beta responses and event-related filtered beta responses were significantly higher in responses to target than non-target stimuli (p < 0.05). In MCI patients, there were no differences in evoked beta power between target and non-target stimuli. Furthermore, upon presentation of visual oddball paradigm, occipital electrodes depict higher beta response in comparison to other electrode sites. The increased beta response upon presentation of target stimuli in healthy subjects implies that beta oscillations could shift the system to an attention state, and had important function in cognitive activity. This may, in future, open the way to consider beta activity as an important operator in brain cognitive processes. PMID:24179847

Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma.

PubMed Central

Altomonte, M.; Montagner, R.; Fonsatti, E.; Colizzi, F.; Cattarossi, I.; Brasoveanu, L. I.; Nicotra, M. R.; Cattelan, A.; Natali, P. G.; Maio, M.

1996-01-01

Human endoglin (CD105) is a member of the transforming growth factor beta (TGF-beta) receptor family that binds TGF-beta1 and -beta3, but not TGF-beta2, on human endothelial cells. Immunohistochemical analyses demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAEND3, stained 50, 25 and 34% of intradermal naevi, primary and metastatic melanomas investigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that CD105 expressed by melanoma cells consists of a homodimeric protein with an apparent molecular weight of 180 and 95 kDa under non-reducing and reducing conditions. Cross-linking of 125I-labelled TGF-beta1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DSS) demonstrated that CD105 expressed on pigmented cells binds TGF-beta1; the pattern of binding of TGF-beta1 to melanoma cells was found to be similar to that of human umbilical vein endothelial cells. The addition of exogenous, bioactive TGF-beta1 significantly (P<0.05) inhibited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altogether, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma cells by regulating their sensitivity to TGF-betas. Images Figure 1 Figure 3 Figure 4 PMID:8932339

The first armadillo repeat is involved in the recognition and regulation of beta-catenin phosphorylation by protein kinase CK1.

PubMed

Bustos, Victor H; Ferrarese, Anna; Venerando, Andrea; Marin, Oriano; Allende, Jorge E; Pinna, Lorenzo A

2006-12-26

Multiple phosphorylation of beta-catenin by glycogen synthase kinase 3 (GSK3) in the Wnt pathway is primed by CK1 through phosphorylation of Ser-45, which lacks a typical CK1 canonical sequence. Synthetic peptides encompassing amino acids 38-64 of beta-catenin are phosphorylated by CK1 on Ser-45 with low affinity (K(m) approximately 1 mM), whereas intact beta-catenin is phosphorylated at Ser-45 with very high affinity (K(m) approximately 200 nM). Peptides extended to include a putative CK1 docking motif (FXXXF) at 70-74 positions or a F74AA mutation in full-length beta-catenin had no significant effect on CK1 phosphorylation efficiency. beta-Catenin C-terminal deletion mutants up to residue 181 maintained their high affinity, whereas removal of the 131-181 fragment, corresponding to the first armadillo repeat, was deleterious, resulting in a 50-fold increase in K(m) value. Implication of the first armadillo repeat in beta-catenin targeting by CK1 is supported in that the Y142E mutation, which mimics phosphorylation of Tyr-142 by tyrosine kinases and promotes dissociation of beta-catenin from alpha-catenin, further improves CK1 phosphorylation efficiency, lowering the K(m) value to <50 nM, approximating the physiological concentration of beta-catenin. In contrast, alpha-catenin, which interacts with the N-terminal region of beta-catenin, prevents Ser-45 phosphorylation of CK1 in a dose-dependent manner. Our data show that the integrity of the N-terminal region and the first armadillo repeat are necessary and sufficient for high-affinity phosphorylation by CK1 of Ser-45. They also suggest that beta-catenin association with alpha-catenin and beta-catenin phosphorylation by CK1 at Ser-45 are mutually exclusive.

Effect of dialyzer membranes on beta-2 microglobulin production in Thai hemodialysis patients.

PubMed

Domrongkitchaiporn, S; Chuncharunee, S; Archararit, N; Atamasirikul, K; Vanichakarn, S

1997-09-01

Responses to different types of dialyzer membranes in an Asian population may differ from those of a Caucasian population. Comparative studies on the effects of different dialyzer membranes on beta-2 microglobulin production are also limited. Therefore, we conducted this study to determine the effects of different dialyzer membranes on in vitro mononuclear cell production of beta-2 microglobulin in 9 Thai hemodialysis patients. Each patient was dialysed with 4 different types of dialyzer, including cuprophane (CUP), cellulose diacetate (CD), polysulphone (PS), and polyacrylonitrile membrane (PAN), each for a 1-month period in a randomized sequence. Mononuclear cell culture was done by taking an immediate post-dialysis blood sample at the end of the 1-month period. Beta-2 microglobulin production from cell culture was determined 24 hours later. Mononuclear cell culture and determination of beta-2 microglobulin production from the culture were also done in 10 normal controls and 10 predialysis ESRD patients. The beta-2 microglobulin productions (microgram/L) were shown as follows; Control CUP CD PS PAN [table: see text] (*p < 0.05 compared to cuprophane membrane). polysulphone and polyacrylonitrile membrane induced significantly less beta-2 microglobulin production compared to cuprophane and slightly less compared to cellulose diacetate membrane.

Drug testing data from the 2007 Pan American Games: delta13C values of urinary androsterone, etiocholanolone and androstanediols determined by GC/C/IRMS.

PubMed

Aguilera, Rodrigo; Chapman, Thomas E; Pereira, Henrique; Oliveira, Giselle C; Illanes, Renata P; Fernandes, Telma F; Azevedo, Débora A; Neto, Francisco Aquino

2009-07-01

The main purpose of this article is to show the application of the CG/C/IRMS in real time during competition in the steroid confirmation analysis. For this reason, this paper summarizes the results obtained from the doping control analysis during the period of the 2007 Pan American Games held in Rio de Janeiro, Brazil. Approximately 5600 athletes from 42 different countries competed in the games. Testing was performed in accordance to World Anti-Doping Agency (WADA) technical note for prohibited substances. This paper reports data where abnormal urinary steroid profiles, have been found with the screening procedures. One 8 mL urine sample was used for the analysis of five steroid metabolites with two separate analyses by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). Urine samples were submitted to GC/C/IRMS for confirmation analysis to determine the (13)C/(12)C ratio of selected steroids. Fifty-seven urine samples were analyzed by GC/C/IRMS and the delta(13)C values ( per thousand) of androsterone, etiocholanolone, 5beta-androstane-3alpha, 17beta-diol (5beta-diol), 5alpha-androstane-3alpha, 17beta-diol (5alpha-diol) and 5beta-pregnane-3alpha, 20alpha-diol (5beta-pdiol), the endogenous reference compound are presented. One urine sample with a testosterone/epitestosterone (T/E) ratio of 4.7 was confirmed to be positive of doping by GC/C/IRMS analysis. The delta values of 5beta-diol and 5alpha-diol were 3.8 and 10.8, respectively, compared to the endogenous reference compound 5beta-pdiol, which exceeded the WADA limit of 3 per thousand. The results obtained by CG/C/IRMS confirmation analyses, in suspicious samples, were conclusive in deciding whether or not a doping steroid violation had occurred.

Increased oral AUC of baicalin in streptozotocin-induced diabetic rats due to the increased activity of intestinal beta-glucuronidase.

PubMed

Liu, Li; Deng, Yuan-Xiong; Liang, Yan; Pang, Xiao-Yan; Liu, Xiao-Dong; Liu, Yao-Wu; Yang, Jian-Song; Xie, Lin; Wang, Guang-Ji

2010-01-01

The purpose of the study was to investigate the pharmacokinetics of baicalin, a major bioactive component of Scutellariae radix, in diabetic conditions. The 4-week diabetic rats were induced by intraperitoneal administration of streptozotocin. Plasma concentrations of baicalin were measured following oral (200 mg/kg) or intravenous (12 mg/kg) administration. Everted intestinal transport, intestinal mucosal metabolism of baicalin and intestinal beta-glucuronidase activity were also investigated. It was found that the diabetic condition significantly increased the exposure of baicalin following oral doses (AUC 100.77 +/- 4.16 microg x h/mL in diabetic rats vs. 48.48 +/- 7.94 microg x h/mL in normal rats). In contrast, the diabetic condition significantly decreased the exposure of baicalin following intravenous doses (AUC 11.20 +/- 2.28 microg x h/mL in diabetic rats vs. 18.02 +/- 3.45 microg x h/mL in normal rats). We also found lower apparent permeability coefficients of baicalin in the ileum of diabetic rats (8.43 x 10 (-6) +/- 2.40 x 10 (-6) cm/s in diabetic rats vs. 5.21 x 10 (-5) +/- 1.55 x 10 (-5) cm/s in normal rats). Further studies showed that the diabetic condition enhanced the hydrolysis of baicalin to baicalein in intestinal mucosal, accompanied by an increase of beta-glucuronidase activity. All these results suggested that the higher oral exposure of baicalin in diabetic rats did not result from the decreased hepatic metabolism or increased intestinal absorption of baicalin. The enhancement of intestinal beta-glucuronidase activity may partly account for the higher exposure of baicalin in diabetic rats after oral administration. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Development of in-vitro models to elucidate mechanisms of intrinsic cellular and tissue fluorescence

NASA Astrophysics Data System (ADS)

Savage, Howard E.; Kolli, Venkateswara; Saha, Sanjoy; Zhang, Jian C.; Glasgold, Mark; Sacks, Peter G.; Alfano, Robert R.; Schantz, Stimson P.

1995-04-01

In vitro cell model systems have been used to study the mechanisms of intrinsic cellular and tissue fluorescence as a potential biomarker for cancer. Phenotypic characteristics of cancer that are different from normal tissue include changes in histoarchitecture, proliferation rates and differentiation. a nitrosmethlybenzylamine (NMBA)/rat esophageal carcinogenesis model (NMBA), a transforming growth factor beta (TGF- (beta) )/normal epithelial cell model, and a retinoic acid (RA)/multicellular tumor spheroid model (RAMTS) were used to assess fluorescence changes associated respectively with changes in histoarchitecture, proliferation rates and differentiation. A xenon based fluorescence spectrophotometer (Mediscience Corp.) was used to collect excitation and emission spectra. Two excitation scans ((lambda) Ex 200-360 nm, (lambda) Em 380 nm; (lambda) Ex 240-430 nm, (lambda) Em 450 nm) and two emission scans ((lambda) Ex 300 nm, (lambda) Em 320-580 nm; (lambda) Ex 340 nm, (lambda) Em 360-660 nm) were used to analyze the three model systems. Using the NMBA model. Differences were seen in the excitation scan ((lambda) Ex 200-360 nm, (lambda) Em 380 nm) and the emission scan ((lambda) Ex 340 nm, (lambda) Em 360-660 nm) when normal rat esophageal tissue was compared to hyperplastic and tumor tissue. In the (TGF-(beta) ) model, differences were seen in the excitation scan ((lambda) Ex 240-430 nm, (lambda) Em 450 nm) when comparing proliferation slowed (TGF-(beta) treated) epithelial cells to their untreated controls. In the RAMTS model, differences were seen with all four scans when RA treated multicellular tumor spheroids (nondifferentiating) were compared to untreated control cells (differentiating). The data indicate that fluorescence changes seen in these model systems may relate to changes in histoarchitecture, proliferation rates and differentiation. Their relationship to in vivo fluorescence changes seen in cancer patients remains to be elucidated.

Decreased interleukin-7 and transforming growth factor-beta1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid. Opposite behavior of TNF-alpha, interleukin-4 and interleukin-10.

PubMed

Giacalone, B; D'Auria, L; Bonifati, C; Ferraro, C; Riccardi, E; Mussi, A; D'Agosto, G; Cordiali-Fei, P; Ameglio, F

1998-08-01

This study analyzes both the blister fluid (BF) and serum levels of IL-7 and TGF-beta1 in samples from 18 patients affected with bullous pemphigoid (BP). These cytokines clearly present lower concentrations (P<0.001) in BFs than in the sera (1/20 and 1/2, respectively). In contrast, TNF-alpha, IL-10 and IL-4 present increased amounts in BFs that were 12, 12 and 17-fold, respectively. Eighteen sera (and 10 suction BF) from normal individuals were also employed as control. Normal sera presented significantly lower serum IL-7 concentrations than BP, while no significant TGF-beta1 variations were observed between normal and pathologic serum samples. In addition, the serum levels detected in BP patients were significantly correlated with disease intensity (r=0.64, P=0.003, evaluated as the number of blisters/erosions for each patient) as well as with the peripheral B-lymphocyte counts (r=0.80, P<0.001) and antibodies directed against the basement membrane zone (r=0.65, P<0.005). Although a clear explanation of this phenomenon is lacking, the data presented in this report agree with a strong decrease of IL-7 production at the local level (keratinocyte is known to produce IL-7 and the latter is known to be down-regulated by IL-10, and in other models also by TGF-beta1 and IL-4, whose levels are elevated in BP BFs) as opposed to an increased peripheral release of the same modulator. The IL-7 reduction may have a biological relevance in controlling a chronic, progressive disease.

Plasma progesterone levels and luteal activity during gestation and prolonged oviductal egg retention in a tropical lizard, Calotes versicolor.

PubMed

Shanbhag, B A; Radder, R S; Saidapur, S K

2001-07-01

Plasma progesterone (P) levels and luteal and adrenal activities were studied during normal gestation and unusual prolonged period of oviductal egg retention in a polyautochronic, multiclutched lizard, Calotes versicolor. The normal gestation period (approximately 15 days) was categorized into four stages: stage I--a few hours following ovulation, stage II--eggs with shell and embryo at primitive streak, stage III--embryonic stages 16-20, and stage IV--prior to ovipostion (stages 26-27). The gravid lizards maintained in captivity retained eggs in their oviducts for 45 days. Plasma P levels were low in stage I, increased significantly during stage II, declined in stage III, and reached their lowest in stage IV of gestation. 3Beta-hydroxysteroid dehydrogenase (3beta-HSDH) activity was greater in lutein cells at stage II and was present in traces in stage IV gestation. Interestingly, plasma P titers that were high in lizards with eggs retained longer though the corpora lutea (CL) showed a trace 3beta-HSDH activity. However, 3beta-HSDH activity was greater in the adrenocortical cells in these lizards than that in lizards during a normal gestation period. The present study on C. versicolor shows that the CL remains active and secretes P only during the early part of the gestation. The drop in P level during the later part of gestation might facilitate growth of a second set of vitellogenic follicles. During unfavorable conditions when the lizards are forced to retain eggs in the oviduct, the adrenal glands seem to secrete progesterone to help in egg retention and in inhibition of oviposition.

Acacia nilotica leave extract and glyburide: comparison of fasting blood glucose, serum insulin, beta-thromboglubulin levels and platelet aggregation in streptozotocin induced diabetic rats.

PubMed

Asad, Munnaza; Munir, Tahir Ahmad; Afzal, Nasir

2011-03-01

To evaluate the hypoglycaemic and anti-platelet aggregation effect of aqueous methanol extract of Acacia Nilotica (AN) leaves compared with glyburide on streptozotocin induced diabetic rats. Diabetes mellitus was induced in 90 out of 120 albino rats by administering 50 mg/kg body weight (b.w) streptozotocin and was confirmed by measuring fasting blood glucose level >200 mg/dL on 4th post-induction day. The rats were equally divided into 4 groups, A (normal control), B (diabetic control), C (diabetic rats treated with AN extract) and group D (diabetic rats treated with glyburide). The rats of group C and D were given 300 mg/kg b.w AN extract and 900 microgm/kg b.w glyburide respectively for 3 weeks. Blood glucose was measured by glucometer, platelet aggregation by Dia-Med method and insulin and beta-thromboglobulin by ELISA technique. A significant increase (p<0.05) in fasting blood glucose, beta-thromboglobulin and platelet aggregation and a significant decrease (p<0.05) in insulin levels was observed in streptozotocin induced diabetic rats than the normal controls. The rats treated with AN extract and glyburide showed a significant decrease (p<0.05) in fasting blood glucose and increase (p<0.05) in insulin levels than the diabetic control rats. However, the levels in both the treatment groups remained significantly different than the normal controls. A significant decrease (p<0.05) in beta-thromboglobulin levels was seen in diabetic rats treated with glyburide than the diabetic control rats and diabetic rats treated with AN extract. AN leaves extract result into hypoglycaemic and anti-platelet aggregation activity in diabetic rats as that of glyburide.

Coexistence of Southeast Asian ovalocytosis and beta-thalassemia: a molecular and hematological analysis.

PubMed

Fucharoen, Goonnapa; Fucharoen, Supan; Singsanan, Sanita; Sanchaisuriya, Kanokwan

2007-05-01

We describe hematological and molecular characterization of a Thai female who had Southeast Asian ovalocytosis (SAO) associated with beta+-thalassemia trait. The proband had mild microcytosis with Hb 12.9 g/dl, Hct 35.8%, MCV 74.4 fl, MCH 26.8 pg, MCHC 36.0 g/dl, and elevated Hb A2 (5.6%), characteristics of beta-thalassemia trait. Peripheral blood film examination revealed prominent ovalocytosis. However, a one-tube osmotic fragility (OF) test commonly used for thalassemia screening was negative and a normal OF curve was observed. Further polymerase chain reaction (PCR) analyses identified the beta(-28A-G) mutation in the beta-globin gene and a 27 bp deletion in erythrocyte band 3 protein gene, indicating a genetically compound heterozygote. Hematological data of the proband was comparatively presented with those of eight female and 15 male carriers of pure beta-thalassemia with the same mutation. The finding demonstrates that although the association of the SAO and beta-thalassemia does not produce a more severe clinical picture, this could lead to a mis-screening of beta-thalassemia using an OF test as a primary screening test. Additional blood film examination followed by PCR could help in the detection of this unusual genetic interaction in the region. (c) 2006 Wiley-Liss, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baserga, S.J.; Benz, E.J. Jr.

A number of premature translation termination mutations (nonsense mutations) have been described in the human {alpha}- and {beta}-globin genes. Studies on mRNA isolated from patients with {beta}{sup 0}-thalassemia have shown that for both the {beta}-17 and the {beta}-39 mutations less than normal levels of {beta}-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human {beta}-globin mRNA). In vitro studies using the cloned {beta}-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. Themore » authors have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, they have studied the effect of five nonsense mutations and two missense mutations on the expression of human {beta}-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation.« less

Exercise testing after beta-blockade: improved specificity and predictive value in detecting coronary heart disease.

PubMed Central

Marcomichelakis, J; Donaldson, R; Green, J; Joseph, S; Kelly, H B; Taggart, P; Somerville, W

1980-01-01

The value of exercise testing in detecting myocardial ischaemia resulting from coronary atheroma remains controversial. In order to increase the reliability of exercise testing, all its components (asymptomatic, haemodynamic, and electrocardiographic) have been scrutinised. In this study, concerned only with the electrocardiographic response to exercise, the incorporation of beta-blockade into the standard exercise procedure has improved specificity and predictive value without affecting sensitivity. Fifty patients with anginal pain and 50 asymptomatic subjects with an abnormal electrocardiogram were investigated by exercise testing before and after beta-blockade (oxprenolol). All subjects had coronary arteriograms and left ventriculograms, and the results of exercise testing were related to the presence or absence of obstructive coronary artery disease. Possible causes of false positive exercise tests were eliminated by echocardiography. Though beta-blockade was unreliable in distinguishing ischaemic from non-ischaemic resting electrocardiograms, it eliminated all the false positive electrocardiographic responses to exercise in both groups and did not abolish any of the true positive electrocardiographic responses. Thus, specificity and predictive value were improved without reduction in sensitivity. This technique may not necessarily be applicable to other groups of patients or to a random population, but the results of this study suggest it will be a useful additional routine procedure in the investigation of coronary heart disease. PMID:7437172

IRAS sky survey atlas: Explanatory supplement

NASA Technical Reports Server (NTRS)

Wheelock, S. L.; Gautier, T. N.; Chillemi, J.; Kester, D.; Mccallon, H.; Oken, C.; White, J.; Gregorich, D.; Boulanger, F.; Good, J.

1994-01-01

This Explanatory Supplement accompanies the IRAS Sky Survey Atlas (ISSA) and the ISSA Reject Set. The first ISSA release in 1991 covers completely the high ecliptic latitude sky, absolute value of beta is greater than 50 deg, with some coverage down to the absolute value of beta approx. equal to 40 deg. The second ISSA release in 1992 covers ecliptic latitudes of 50 deg greater than the absolute value of beta greater than 20 deg, with some coverage down to the absolute value of beta approx. equal to 13 deg. The remaining fields covering latitudes within 20 deg of the ecliptic plane are of reduced quality compared to the rest of the ISSA fields and therefore are released as a separate IPAC product, the ISSA Reject Set. The reduced quality is due to contamination by zodiacal emission residuals. Special care should be taken when using the ISSA Reject images. In addition to information on the ISSA images, some information is provided in this Explanatory Supplement on the IRAS Zodiacal History File (ZOHF), Version 3.0, which was described in the December 1988 release memo. The data described in this Supplement are available at the National Space Science Data Center (NSSDC) at the Goddard Space Flight Center. The interested reader is referred to the NSSDC for access to the IRAS Sky Survey Atlas (ISSA).

Decreased intelligence in children and exposure to fluoride and arsenic in drinking water.

PubMed

Rocha-Amador, Diana; Navarro, Maria Elena; Carrizales, Leticia; Morales, Raúl; Calderón, Jaqueline

2007-01-01

Recent evidence suggests that fluoride (F) and arsenic (As) may adversely affect intelligence quotient (IQ) scores. We explore the association between exposure to F and As in drinking water and intelligence in children. Three rural communities in Mexico with contrasting levels of F and As in drinking water were studied: Moctezuma (F 0.8+/-1.4 mg/L; As 5.8+/-1.3 microg/L); Salitral (F 5.3+/-0.9 mg/L; As 169+/-0.9 microg/L) and 5 de Febrero (F 9.4+/-0.9 mg/L; As 194+/-1.3 microg/L). The final study sample consisted of 132 children from 6 to 10 years old. After controlling for confounders, an inverse association was observed between F in urine and Performance, Verbal, and Full IQ scores (beta values = -13, -15.6, -16.9, respectively). Similar results were observed for F in drinking water (beta values = -6.7, -11.2, -10.2, respectively) and As in drinking water (beta values= -4.30, -6.40, -6.15, respectively). The p-values for all cases were < 0.001. A significant association was observed between As in urine and Full IQ scores (beta = -5.72, p = 0.003). These data suggest that children exposed to either F or As have increased risks of reduced IQ scores.

Right ventricular beneficial effects of beta adrenergic receptor kinase inhibitor (betaARKct) gene transfer in a rat model of severe pressure overload.

PubMed

Molina, Ezequiel J; Gupta, Dipin; Palma, Jon; Gaughan, John P; Macha, Mahender

2009-06-01

Heart failure is associated with abnormalities in betaAR cascade regulation, calcium cycling, expression of inflammatory mediators and apoptosis. Adenoviral mediated gene transfer of betaARKct has beneficial indirect effects on these pathologic processes upon the left ventricular myocardium. The concomitant biochemical changes that occur in the right ventricle have not been well characterized. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After a decrease in fractional shortening of 25% from baseline, intracoronary injection of adenoviral-betaARKct (n=14) or adenoviral-beta-galactosidase (control, n=13) was performed. Rats were randomly euthanized on post-operative day 7, 14 or 21. Protein analysis including RV myocardial levels of betaARKct, betaARK1, SERCA(2a), inflammatory tissue mediators (IL-1, IL-6 and TNF-alpha), apoptotic markers (bax and bak), and MAP kinases (jnk, p38 and erk) was performed. ANOVA was employed for group comparison. Adenoviral-betaARKct treated animals showed increased expression of betaARKct and decreased levels of betaARK1 compared with controls. This treatment group also demonstrated normalization of SERCA(2a) expression and decreased levels of the inflammatory markers IL-1, IL-6 and TNF-alpha. The pro-apoptotic markers bax and bak were similarly improved. Ventricular levels of the MAP kinase jnk were increased. Differences were most significant 7 days after gene transfer, but the majority of these changes persisted at 21 days. These results suggest that attenuation of the pathologic mechanisms of beta adrenergic receptor desensitization, SERCA(2a) expression, inflammation and apoptosis, not only occur in the left ventricle but also in the right ventricular myocardium after intracoronary gene transfer of betaARKct during heart failure.

A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia.

PubMed

Lemper, Marie; De Groef, Sofie; Stangé, Geert; Baeyens, Luc; Heimberg, Harry

2016-09-01

When the beta cell mass or function declines beyond a critical point, hyperglycaemia arises. Little is known about the potential pathways involved in beta cell rescue. As two cytokines, epidermal growth factor (EGF) and ciliary neurotrophic factor (CNTF), restored a functional beta cell mass in mice with long-term hyperglycaemia by reprogramming acinar cells that transiently expressed neurogenin 3 (NGN3), the current study assesses the effect of these cytokines on the functional beta cell mass after an acute chemical toxic insult. Glycaemia and insulin levels, pro-endocrine gene expression and beta cell origin, as well as the role of signal transducer and activator of transcription 3 (STAT3) signalling, were assessed in EGF+CNTF-treated mice following acute hyperglycaemia. The mice were hyperglycaemic 1 day following i.v. injection of the beta cell toxin alloxan, when the two cytokines were applied. One week later, 68.6 ± 4.6% of the mice had responded to the cytokine treatment and increased their insulin(+) cell number to 30% that of normoglycaemic control mice, resulting in restoration of euglycaemia. Although insulin(-) NGN3(+) cells appeared following acute EGF+CNTF treatment, genetic lineage tracing showed that the majority of the insulin(+) cells originated from pre-existing beta cells. Beta cell rescue by EGF+CNTF depends on glycaemia rather than on STAT3-induced NGN3 expression in acinar cells. In adult mice, EGF+CNTF allows the rescue of beta cells in distress when treatment is given shortly after the diabetogenic insult. The rescued beta cells restore a functional beta cell mass able to control normal blood glucose levels. These findings may provide new insights into compensatory pathways activated early after beta cell loss.

Beta-blocking agents in patients with insulin resistance: effects of vasodilating beta-blockers.

PubMed

Jacob, S; Balletshofer, B; Henriksen, E J; Volk, A; Mehnert, B; Löblein, K; Häring, H U; Rett, K

1999-01-01

Essential hypertension is--at least in many subjects--associated with a decrease in insulin sensitivity, while glycaemic control is (still) normal. It seems that in hypertensive patients, two major functions of insulin are impaired: there is insulin resistance of peripheral glucose uptake (primarily skeletal muscle) and insulin resistance of insulin-stimulated vasodilation. In view of some retrospective data and meta-analyses, which showed a less than expected reduction in coronary events (coronary paradox), the metabolic side effects of the antihypertensive treatment have received more attention. Many groups have shown that conventional antihypertensive treatment, both with beta-blockers and/or diuretics, decreases insulin sensitivity by various mechanisms. While low-dose diuretics seem to be free of these metabolic effects, there is no evidence for this in the beta-adrenergic blockers. However, recent metabolic studies evaluated the effects of vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. None of them decreased insulin sensitivity, as has been described for the beta-blockers with and without beta1 selectivity. This supports the idea that peripheral vascular resistance and peripheral blood flow play a central role in mediating the metabolic side effects of the beta-blocking agents, as the vasodilating action (either via beta2 stimulation or alpha1-blockade) seems to more than offset the detrimental effects of the blockade of beta (or beta1) receptors. Further studies are needed to elucidate the relevance of the radical scavenging properties of these agents and their connection to their metabolic effects. Therefore, the beneficial characteristics of these newer beta-adrenoreceptor blockers suggest that the vasodilating beta-blocking agents could be advantageous for hypertensive patients with insulin resistance or type 2 diabetes.

Is Serum Zinc Level Associated with Prediabetes and Diabetes?: A Cross-Sectional Study from Bangladesh

PubMed Central

Islam, Md. Rafiqul; Arslan, Iqbal; Attia, John; McEvoy, Mark; McElduff, Patrick; Basher, Ariful; Rahman, Waliur; Peel, Roseanne; Akhter, Ayesha; Akter, Shahnaz; Vashum, Khanrin P.; Milton, Abul Hasnat

2013-01-01

Aims To determine serum zinc level and other relevant biological markers in normal, prediabetic and diabetic individuals and their association with Homeostasis Model Assessment (HOMA) parameters. Methods This cross-sectional study was conducted between March and December 2009. Any patient aged ≥30 years attending the medicine outpatient department of a medical university hospital in Dhaka, Bangladesh and who had a blood glucose level ordered by a physician was eligible to participate. Results A total of 280 participants were analysed. On fasting blood sugar results, 51% were normal, 13% had prediabetes and 36% had diabetes. Mean serum zinc level was lowest in prediabetic compared to normal and diabetic participants (mean differences were approximately 65 ppb/L and 33 ppb/L, respectively). In multiple linear regression, serum zinc level was found to be significantly lower in prediabetes than in those with normoglycemia. Beta cell function was significantly lower in prediabetes than normal participants. Adjusted linear regression for HOMA parameters did not show a statistically significant association between serum zinc level, beta cell function (P = 0.07) and insulin resistance (P = 0.08). Low serum zinc accentuated the increase in insulin resistance seen with increasing BMI. Conclusion Participants with prediabetes have lower zinc levels than controls and zinc is significantly associated with beta cell function and insulin resistance. Further longitudinal population based studies are warranted and controlled trials would be valuable for establishing whether zinc supplementation in prediabetes could be a useful strategy in preventing progression to Type 2 diabetes. PMID:23613929

Investigation of compositional segregation during unidirectional solidification of solid solution semiconducting alloys

NASA Technical Reports Server (NTRS)

Wang, J. C.

1982-01-01

Compositional segregation of solid solution semiconducting alloys in the radial direction during unidirectional solidification was investigated by calculating the effect of a curved solid liquid interface on solute concentration at the interface on the solid. The formulation is similar to that given by Coriell, Boisvert, Rehm, and Sekerka except that a more realistic cylindrical coordinate system which is moving with the interface is used. Analytical results were obtained for very small and very large values of beta with beta = VR/D, where V is the velocity of solidification, R the radius of the specimen, and D the diffusivity of solute in the liquid. For both very small and very large beta, the solute concentration at the interface in the solid C(si) approaches C(o) (original solute concentration) i.e., the deviation is minimal. The maximum deviation of C(si) from C(o) occurs for some intermediate value of beta.

High-Precision Half-Life Measurement for the Superallowed {beta}{sup +} Emitter {sup 26}Al{sup m}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finlay, P.; Svensson, C. E.; Green, K. L.

2011-01-21

A high-precision half-life measurement for the superallowed {beta}{sup +} emitter {sup 26}Al{sup m} was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T{sub 1/2}=6346.54{+-}0.46{sub stat{+-}}0.60{sub syst} ms, consistent with, but 2.5 times more precise than, the previous world average. The {sup 26}Al{sup m} half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed {beta} decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for {sup 26}Al{sup m}, 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi {beta}-decay studies used to test the conserved vector current hypothesismore » and determine the V{sub ud} element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.« less

The beta(+) decay and cosmic-ray half-life of Mn-54

NASA Astrophysics Data System (ADS)

Dacruz, M. T. F.; Norman, E. B.; Chan, Y. D.; Garcia, A.; Larimer, R. M.; Lesko, K. T.; Stokstad, R. G.; Wietfeldt, F. E.

1993-03-01

We performed a search for the beta(+) branch of Mn-54 decay. As a cosmic ray, Mn-54, deprived of its atomic electrons, can decay only via beta(+) and beta(-) decay, with a half-life of the order of 106 yr. This turns Mn-54 into a suitable cosmic chronometer for the study of cosmic-ray confinement times. We searched for coincident back-to-back 511-keV gamma-rays using two germanium detectors inside a Nal(Tl) annulus. An upper limit of 2 x 10-8 was found for the beta(+) decay branch, corresponding to a lower limit of 13.7 for the log ft value.

Low Background Signal Readout Electronics for the MAJORANA DEMONSTRATOR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guinn, I.; Abgrall, N.; Avignone, III, F. T.

The MAJORANA DEMONSTRATOR is a planned 40 kg array of Germanium detectors intended to demonstrate the feasibility of constructing a tonne-scale experiment that will seek neutrinoless double beta decay (0 nu beta beta) in Ge-76. Such an experiment would require backgrounds of less than 1 count/tonne-year in the 4 keV region of interest around the 2039 keV Q-value of the beta beta decay. Designing low-noise electronics, which must be placed in close proximity to the detectors, presents a challenge to reaching this background target. This paper will discuss the MAJORANA collaboration's solutions to some of these challenges.

Stabilization of beta-catenin induces pancreas tumor formation.

PubMed

Heiser, Patrick W; Cano, David A; Landsman, Limor; Kim, Grace E; Kench, James G; Klimstra, David S; Taketo, Maketo M; Biankin, Andrew V; Hebrok, Matthias

2008-10-01

beta-Catenin signaling within the canonical Wnt pathway is essential for pancreas development. However, the pathway is normally down-regulated in the adult organ. Increased cytoplasmic and nuclear localization of beta-catenin can be detected in nearly all human solid pseudopapillary neoplasms (SPN), a rare tumor with low malignant potential. Conversely, pancreatic ductal adenocarcinoma (PDA) accounts for the majority of pancreatic tumors and is among the leading causes of cancer death. Whereas activating mutations within beta-catenin and other members of the canonical Wnt pathway are rare, recent reports have implicated Wnt signaling in the development and progression of human PDA. Here, we sought to address the role of beta-catenin signaling in pancreas tumorigenesis. Using Cre/lox technology, we conditionally activated beta-catenin in a subset of murine pancreatic cells in vivo. Activation of beta-catenin results in the formation of large pancreatic tumors at a high frequency in adult mice. These tumors resemble human SPN based on morphologic and immunohistochemical comparisons. Interestingly, stabilization of beta-catenin blocks the formation of pancreatic intraepithelial neoplasia (PanIN) in the presence of an activating mutation in Kras that is known to predispose individuals to PDA. Instead, mice in which beta-catenin and Kras are concurrently activated develop distinct ductal neoplasms that do not resemble PanIN lesions. These results demonstrate that activation of beta-catenin is sufficient to induce pancreas tumorigenesis. Moreover, they indicate that the sequence in which oncogenic mutations are acquired has profound consequences on the phenotype of the resulting tumor.

Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.

PubMed

Takashima, Seiki; Schlidt, Scott A; Koukoulis, Giovanna; Sevala, Mayura; Egan, Thomas M

2005-06-01

If lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of beta-stimulation, or would persist despite beta-blockade. Donor rats were treated intraperitoneally with beta-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the beta-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP. Lungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with beta-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of beta-blockade. Lung cAMP levels were increased only with iso in the absence of beta-blockade. The attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of beta-blockade, and may not be a result of beta-stimulated increased cAMP.

Effects of low intensity laser acupoint irradiation on inhibiting islet beta-cell apoptosis in rats with type 2 diabetes

NASA Astrophysics Data System (ADS)

Xiong, Guoxin; Xiong, Leilei; Li, Xinzhong

2016-09-01

To investigate the effects of low intensity semiconductor laser acupoint irradiation on inhibiting islet beta-cell apoptosis in rats with type 2 diabetes, a method using a high-fat diet and low-dose intraperitoneal injections of streptozotocin established a type 2 diabetes mellitus rat model. Model rats were randomly divided into a laser acupoint irradiation group, rosiglitazone control group, and placebo group; each group had 10 rats. In addition, 10 normal male rats were selected for the normal control group. The Housanli, Neiting and Yishu acupoints of the rats in the laser acupoint irradiation group were irradiated with a 10 mW semiconductor laser; each point was irradiated for 15 min, once every 2 d over 28 d, for a total of 14 episodes of irradiation. The rosiglitazone group rats were given rosiglitazone (0.2 mg kg-1) intragastrically; the placebo group rats were given 0.9% brine (0.2 mg kg-1) intragastrically, once daily, for four consecutive weeks. The change of fasting blood glucose was determined before and after each treatment. The islet beta-cell apoptosis was determined. The islet beta-cell apoptosis rates of the laser acupoint irradiation group and the rosiglitazone group were significantly lower than the rate of the placebo group. Even though the rate was lower in the laser acupoint irradiation group than in the rosiglitazone group, there was no significant difference between them. It is shown that acupoint irradiation with a semiconductor laser can effectively inhibit islet beta-cell apoptosis in rats with type 2 diabetes.

Predictors of linear growth in the first year of life of a prospective cohort of full term children with normal birth weight.

PubMed

Queiroz, Valterlinda A O; Assis, Ana Marlúcia O; Pinheiro, Sandra Maria C; Ribeiro, Hugo C Ribeiro

2012-01-01

To investigate covariates that could affect the variation in mean length/age z scores in the first year of life of children born full term with normal birth weight. This was a prospective study of a cohort of mother-infant pairs recruited at public maternity units in two municipalities in the Brazilian state of Bahia, from March 2005 to October 2006. This paper reports the results for linear growth of 489 children who were followed-up for the first 12 months of their lives. A mixed-effect regression model was used to investigate the influence of covariates of mean length/age z score during the first year of life. The multivariate mixed effect analysis indicated that mothers not cohabiting with a partner (beta = 0.2347; p = 0.004) and increased duration of exclusive breastfeeding (beta = 0.0031; p < 0.001) had a positive impact, whereas mother's height less than 150 cm (beta = -0.4393; p < 0.001), birth weight of 2,500-2,999 g (beta = -0.8084; p < 0.001) and anemia in the child (beta = -0.0875; p < 0.001) all had a negative impact on the variation in estimated length/age z score. Therefore, the results of this study indicate that short maternal stature, birth weight < 3,000 g and anemia in the infant had a negative effect on linear growth during the first year of life, whereas longer duration of exclusive breastfeeding and mothers who did not cohabit with a partner had a positive effect.

Beta activity in the premotor cortex is increased during stabilized as compared to normal walking

PubMed Central

Bruijn, Sjoerd M.; Van Dieën, Jaap H.; Daffertshofer, Andreas

2015-01-01

Walking on two legs is inherently unstable. Still, we humans perform remarkable well at it, mostly without falling. To gain more understanding of the role of the brain in controlling gait stability we measured brain activity using electro-encephalography (EEG) during stabilized and normal walking. Subjects walked on a treadmill in two conditions, each lasting 10 min; normal, and while being laterally stabilized by elastic cords. Kinematics of trunk and feet, electro-myography (EMG) of neck muscles, as well as 64-channel EEG were recorded. To assess gait stability the local divergence exponent, step width, and trunk range of motion were calculated from the kinematic data. We used independent component (IC) analysis to remove movement, EMG, and eyeblink artifacts from the EEG, after which dynamic imaging of coherent sources beamformers were determined to identify cortical sources that showed a significant difference between conditions. Stabilized walking led to a significant increase in gait stability, i.e., lower local divergence exponents. Beamforming analysis of the beta band activity revealed significant sources in bilateral pre-motor cortices. Projection of sensor data on these sources showed a significant difference only in the left premotor area, with higher beta power during stabilized walking, specifically around push-off, although only significant around contralateral push-off. It appears that even during steady gait the cortex is involved in the control of stability. PMID:26578937

PEG-rHuMGDF ameliorates thrombocytopenia in carboplatin-treated rats without inducing myelofibrosis.

PubMed

Ide, Y; Harada, K; Imai, A; Yanagida, M

1999-08-01

We examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on carboplatin-induced thrombocytopenia in rats. The focus was on whether myelofibrosis is associated with the PEG-rHuMGDF treatment in this chemotherapy model. After a single injection of carboplatin, rats received subcutaneous PEG-rHuMGDF at pharmacologic doses (1,3, or 30 micrograms/kg) or a vehicle daily for 7 days. PEG-rHuMGDF at more than 3 micrograms/kg ameliorated the thrombocytopenia at day 10. Histologically, no myelofibrosis was detected in the rats treated with PEG-rHuMGDF or vehicle. Subsequently, PEG-rHuMGDF at a suprapharmacologic dose (100 micrograms/kg) was subcutaneously administered to normal and to carboplatin-treated rats daily for 7 days. Histological analysis revealed that the treatment with PEG-rHuMGDF induced myelofibrosis in the normal rats but not in the carboplatin-treated rats. Additionally, the transforming growth factor-beta 1 (TGF-beta 1) levels in the extracellular fluid and the whole extract of the bone marrow were increased to a much lesser degree in the carboplatin-treated rats compared to the normal rats. These findings suggest that PEG-rHuMGDF is effective for carboplatin-induced thrombocytopenia. Proper control of platelet counts and TGF-beta 1 levels is essential so that myelofibrosis is not induced in clinical use.

Self absorption of alpha and beta particles in a fiberglass filter.

PubMed

Luetzelschwab, J W; Storey, C; Zraly, K; Dussinger, D

2000-10-01

Environmental air sampling uses fiberglass filters to collect particulate matter from the air and then a gas flow detector to measure the alpha and beta activity on the filter. When counted, the filter is located close to the detector so the alpha and beta particles emerging from the filter travel toward the detector at angles ranging from zero to nearly 90 degrees to the normal to the filter surface. The particles at small angles can readily pass through the filter, but particles at large angles pass through a significant amount of filter material and can be totally absorbed. As a result, counting losses can be great. For 4 MeV alpha particles, the filter used in this experiment absorbs 43% of the alpha particles; for 7.5 MeV alphas, the absorption is 13%. The measured beta activities also can have significant counting losses. Beta particles with maximum energies of 0.2 and 2.0 MeV have absorptions of 44 and 2%, respectively.

Hydraulic pressure inducing renal tubular epithelial-myofibroblast transdifferentiation in vitro.

PubMed

Li, Fei-yan; Xie, Xi-sheng; Fan, Jun-ming; Li, Zi; Wu, Jiang; Zheng, Rong

2009-09-01

The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) were investigated. We applied hydraulic pressure (50 cm H2O) to normal rat kidney tubular epithelial cells (NRK52E) for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression of myofibroblastic marker protein and transforming growth factor-beta1 (TGF-beta1) of NRK52E cells were examined. Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression of alpha-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-beta1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-beta1. We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-beta1 secretion.

beta. -Adrenoceptors in human tracheal smooth muscle: characteristics of binding and relaxation

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Koppen, C.J.; Hermanussen, M.W.; Verrijp, K.N.

1987-06-29

Specific binding of (/sup 125/I)-(-)-cyanopindolol to human tracheal smooth muscle membranes was saturable, stereo-selective and of high affinity (K/sub d/ = 5.3 +/- 0.9 pmol/l and R/sub T/ = 78 +/- 7 fmol/g tissue). The ..beta../sub 1/-selective antagonists atenolol and LK 203-030 inhibited specific (/sup 125/I)-(-)-cyanopindolol binding according to a one binding site model with low affinity in nearly all subjects, pointing to a homogeneous BETA/sub 2/-adrenoceptor population. In one subject using LK 203-030 a small ..beta../sub 1/-adrenoceptor subpopulation could be demonstrated. The beta-mimetics isoprenaline, fenoterol, salbutamol and terbutaline recognized high and low affinity agonist binding sites. Isoprenaline's pK/sub H/-more » and pK/sub L/-values for the high and low affinity sites were 8.0 +/- 0.2 and 5.9 +/- 0.3 respectively. In functional experiments isoprenaline relaxed tracheal smooth muscle strips having intrinsic tone with a pD/sub 2/-value of 6.63 +/- 0.19. 32 references, 4 figures, 2 tables.« less

The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthritic subchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein.

PubMed

Maxis, Kelitha; Delalandre, Aline; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Duval, Nicolas; Lajeunesse, Daniel

2006-01-01

Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E2 (PGE2) or leukotriene B4 (LTB4) by subchondral osteoblasts, PGE2 levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2 (COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low OA osteoblasts subgroup. The addition of PGE2 to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup. LTB4 levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plus transforming growth factor-beta (TGF-beta), a situation corresponding to their effect on FLAP mRNA levels. Treatments with 1,25(OH)2D3 and TGF-beta also modulated PGE2 production. TGF-beta stimulated PGE2 production in both OA osteoblast groups, whereas 1,25(OH)2D3 alone had a limited effect but decreased the effect of TGF-beta in the low OA osteoblasts subgroup. This modulation of PGE2 production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts compared with normal; however, no relationship was observed overall between IL-18 and PGE2 levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE2 to LTB4 is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is also modulated differently by 1,25(OH)2D3 and TGF-beta depending on their endogenous low and high PGE2 levels.

Spectrofluorimetric determination of stoichiometry and association constants of the complexes of harmane and harmine with beta-cyclodextrin and chemically modified beta-cyclodextrins.

PubMed

Martín, L; León, A; Olives, A I; Del Castillo, B; Martín, M A

2003-06-13

The association characteristics of the inclusion complexes of the beta-carboline alkaloids harmane and harmine with beta-cyclodextrin (beta-CD) and chemically modified beta-cyclodextrins such as hydroxypropyl-beta-cyclodextrin (HPbeta-CD), 2,3-di-O-methyl-beta-cyclodextrin (DMbeta-CD) and 2,3,6-tri-O-methyl-beta-cyclodextrin (TMbeta-CD) are described. The association constants vary from 112 for harmine/DMbeta-CD to 418 for harmane/HPbeta-CD. The magnitude of the interactions between the host and the guest molecules depends on the chemical and geometrical characteristics of the guest molecules and therefore the association constants vary for the different cyclodextrin complexes. The steric hindrance is higher in the case of harmine due to the presence of methoxy group on the beta-carboline ring. The association obtained for the harmane complexes is stronger than the one observed for harmine complexes except in the case of harmine/TMbeta-CD. Important differences in the association constants were observed depending on the experimental variable used in the calculations (absolute value of fluorescence intensity or the ratio between the fluorescence intensities corresponding to the neutral and cationic forms). When fluorescence intensity values were considered, the association constants were higher than when the ratio of the emission intensity for the cationic and neutral species was used. These differences are a consequence of the co-existence of acid-base equilibria in the ground and in excited states together with the complexation equilibria. The existence of a proton transfer reaction in the excited states of harmane or harmine implies the need for the experimental dialysis procedure for separation of the complexes from free harmane or harmine. Such methodology allows quantitative results for stoichiometry determinations to be obtained, which show the existence of both 1:1 and 1:2 beta-carboline alkaloid:CD complexes with different solubility properties.

The relationships between half-life (t1/2) and mean residence time (MRT) in the two-compartment open body model.

PubMed

Sobol, Eyal; Bialer, Meir

2004-05-01

In the one-compartment model following i.v. administration the mean residence time (MRT) of a drug is always greater than its half-life (t(1/2)). However, following i.v. administration, drug plasma concentration (C) versus time (t) is best described by a two-compartment model or a two exponential equation:C=Ae(-alpha t)+Be(-beta t), where A and B are concentration unit-coefficients and alpha and beta are exponential coefficients. The relationships between t(1/2) and MRT in the two-compartment model have not been explored and it is not clear whether in this model too MRT is always greater than t(1/2). In the current paper new equations have been developed that describe the relationships between the terminal t(1/2) (or t(1/2 beta)) and MRT in the two-compartment model following administration of i.v. bolus, i.v. infusion (zero order input) and oral administration (first order input). A critical value (CV) equals to the quotient of (1-ln2) and (1-beta/alpha) (CV=(1-ln2)/(1-beta/alpha)=0.307/(1-beta/alpha)) has been derived and was compared with the fraction (f(1)) of drug elimination or AUC (AUC-area under C vs t curve) associated with the first exponential term of the two-compartment equation (f(1)=A/alpha/AUC). Following i.v. bolus, CV ranges between a minimal value of 0.307 (1-ln2) and infinity. As long as f(1)t(1/2) and vice versa, and when f(1)=CV, then MRT=t(1/2). Following i.v. infusion and oral administration the denominator of the CV equation does not change but its numerator increases to (0.307+beta T/2) (T-infusion duration) and (0.307+beta/ka) (ka-absorption rate constant), respectively. Examples of various drugs are provided. For every drug that after i.v. bolus shows two-compartment disposition kinetics the following conclusions can be drawn (a) When f(1)<0.307, then f(1)t(1/2). (b) When beta/alpha>ln2, then CV>1>f(1) and thus(,) MRT>t(1/2). (c) When ln2>beta/alpha>(ln4-1), then 1>CV>0.5 and thus, in order for t(1/2)>MRT, f(1) has to be greater than its complementary fraction f(2) (f(1)>f(2)). (d) When beta/alpha<(ln4-1), it is possible that t(1/2)>MRT even when f(2)>f(1), as long as f(1)>CV. (e) As beta gets closer to alpha, CV approaches its maximal value (infinity) and therefore, the chances of MRT>t(1/2) are growing. (f) As beta becomes smaller compared with alpha, beta/alpha approaches zero, the denominator approaches unity and consequently, CV gets its minimal value and thus, the chances of t(1/2)>MRT are growing. (g) Following zero and first order input MRT increases compared with i.v. bolus and so does CV and thus, the chances of MRT>t(1/2) are growing. Copyright 2004 John Wiley & Sons, Ltd.

Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.

Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloidmore » fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.« less

Noise-Enhanced Measurement of Weak Doublet Spectra with a Fourier-Transform Spectrometer and a 1-Bit Analog-to-Digital Converter.

PubMed

Lim, M; Saloma, C

2001-04-10

We demonstrate an efficient noise dithering procedure for measuring the power spectrum of a weak spectral doublet with a Fourier-transform spectrometer in which the subthreshold interferogram is measured by a 1-bit analog-to-digital converter without oversampling. In the absence of noise, no information is obtained regarding the doublet spectrum because the modulation term s(x) of its interferogram is below the instrumental detection limit B, i.e., |s(x)| < B, for all path difference x values. Extensive numerical experiments are carried out concerning the recovery of the doublet power spectrum that is represented by s(x) = (s(0)/2)exp(-pi(2)x(2)/beta)[cos(2pif(1)x) + cos(2pif(2)x)], where s(0) is a constant, beta is the linewidth factor, and ?f? = (f(1) + f(2))/2. Different values of ?f?, s(0), and beta are considered to evaluate thoroughly the accuracy of the procedure to determine the unknown values of f(1) and f(2), the spectral linewidth, and the peak values of the spectral profiles. Our experiments show that, even for short observation times, the resonant frequencies of s(x) could be located with high accuracy over a wide range of ?f? and beta values. Signal-to-noise ratios as high as 50 are also gained for the recovered power spectra. The performance of the procedure is also analyzed with respect to another method that recovers the amplitude values of s(x) directly.

Functional characterization of the beta-adrenergic receptor subtypes expressed by CA1 pyramidal cells in the rat hippocampus.

PubMed

Hillman, Kristin L; Doze, Van A; Porter, James E

2005-08-01

Recent studies have demonstrated that activation of the beta-adrenergic receptor (AR) using the selective beta-AR agonist isoproterenol (ISO) facilitates pyramidal cell long-term potentiation in the cornu ammonis 1 (CA1) region of the rat hippocampus. We have previously analyzed beta-AR genomic expression patterns of 17 CA1 pyramidal cells using single cell reverse transcription-polymerase chain reaction, demonstrating that all samples expressed the beta2-AR transcript, with four of the 17 cells additionally expressing mRNA for the beta1-AR subtype. However, it has not been determined which beta-AR subtypes are functionally expressed in CA1 for these same pyramidal neurons. Using cell-attached recordings, we tested the ability of ISO to increase pyramidal cell action potential (AP) frequency in the presence of subtype-selective beta-AR antagonists. ICI-118,551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol] and butoxamine [alpha-[1-(t-butylamino)ethyl]-2,5-dimethoxybenzyl alcohol) hydrochloride], agents that selectively block the beta2-AR, produced significant parallel rightward shifts in the concentration-response curves for ISO. From these curves, apparent equilibrium dissociation constant (K(b)) values of 0.3 nM for ICI-118,551 and 355 nM for butoxamine were calculated using Schild regression analysis. Conversely, effective concentrations of the selective beta1-AR antagonists CGP 20712A [(+/-)-2-hydroxy-5-[2-([2-hydroxy-3-(4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenoxy)propyl]amino)ethoxy]-benzamide methanesulfonate] and atenolol [4-[2'-hydroxy-3'-(isopropyl-amino)propoxy]phenylacetamide] did not significantly affect the pyramidal cell response to ISO. However, at higher concentrations, atenolol significantly decreased the potency for ISO-mediated AP frequencies. From these curves, an apparent atenolol K(b) value of 3162 nM was calculated. This pharmacological profile for subtype-selective beta-AR antagonists indicates that beta2-AR activation is mediating the increased AP frequency. Knowledge of functional AR expression in CA1 pyramidal neurons will aid future long-term potentiation studies by allowing selective manipulation of specific beta-AR subtypes.

Plasma growth hormone, insulin, and glucagon responses to arginine infusion in children and adolescents with idiopathic short stature, isolated growth hormone deficiency, panhypopituitarism, and anorexia nervosa.

PubMed

Sizonenko, P C; Rabinovitch, A; Schneider, P; Paunier, L; Wollheim, C B; Zahnd, G

1975-09-01

The effects of intravenous infusion of arginine (20 g/m2) after an overnight fast on plasma immunoreactive growth hormone (GH), insulin (IRI), and glucagon (IRG), and blood glucose were examined in five groups of children and adolescents: 10 normal individuals, 18 with idiopathic short stature, 6 with isolated growth hormone deficiency, 8 with panhypopituitarism, and 6 with anorexia nervosa. The mean fasting plasma GH concentration was significantly elevated in the group with anorexia nervosa (P less than 0.05), and similar to the value for the normal group in all other groups. After arginine infusion, four- to sixfold increases of plasma GH were observed in the normal children, and similar increases were seen in those with idiopathic short stature as well as in those with anorexia nervosa; whereas, in the children with isolated growth hormone deficiency or panhypopituitarism, there was no significant increase in plasma GH. Fasting blood glucose concentrations were significantly lower than normal in subjects with isolated growth hormone deficiency (P less than 0.05), panhypopituitarism (P less than 0.001), and anorexia nervosa (P less than 0.001), whereas fasting plasma IRI and IRG concentrations were similar to the values in the normal group. Plasma IRI increased eightfold at the end of the 30-min arginine infusion in the normal subjects; the increase was slightly but not significantly less in those with idiopathic short stature, and significantly less in those with isolated growth hormone deficiency (P less than 0.05), panhypopituitarism (P less than 0.001), and anorexia nervosa (P less than 0.05). Arginine infusion resulted in two- to threefold increases of plasma IRG in the normal group, and similar increases were observed in all of the other groups tested. These results suggest that whereas pancreatic beta cell responsiveness may be deficient in children and adolescents with isolated growth hormone deficiency, panhypopituitarism, or anorexia nervosa, pancreatic alpha cell responsiveness, to arginine at least, appears to be intact under these conditions.

TGF-beta and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker regions.

PubMed

Mori, Shigeo; Matsuzaki, Koichi; Yoshida, Katsunori; Furukawa, Fukiko; Tahashi, Yoshiya; Yamagata, Hideo; Sekimoto, Go; Seki, Toshihito; Matsui, Hirofumi; Nishizawa, Mikio; Fujisawa, Jun-ichi; Okazaki, Kazuichi

2004-09-23

Although hepatocyte growth factor (HGF) can act synergistically or antagonistically with transforming growth factor-beta (TGF-beta) signaling, molecular mechanism of their crosstalk remains unknown. Using antibodies which selectively distinguished receptor-regulated Smads (R-Smads) phosphorylated at linker regions from those at C-terminal regions, we herein showed that either HGF or TGF-beta treatment of normal stomach-origin cells activated the JNK pathway, thereafter inducing endogenous R-Smads phosphorylation at linker regions. However, the phosphorylation at their C-terminal regions was not induced by HGF treatment. The activated JNK could directly phosphorylate R-Smads in vitro at the same sites that were phosphorylated in response to TGF-beta or HGF in vivo. Thus, the linker regions of R-Smads were the common phosphorylation sites for HGF and TGF-beta signaling pathways. The phosphorylation induced by simultaneous treatment with HGF and TGF-beta allowed R-Smads to associate with Smad4 and to translocate into the nucleus. JNK pathway involved HGF and TGF-beta-mediated infiltration potency since a JNK inhibitor SP600125 caused the reduction of invasive capacity induced by HGF and TGF-beta signals. Moreover, a combined treatment with HGF and TGF-beta led to a potent increase in plasminogen activator inhibitor type 1 transcriptional activity through Smad3 phosphorylation at the linker region. In contrast, HGF treatment reduced TGF-beta-dependent activation of p15INK4B promoter, in which Smad3 phosphorylation at the C-terminal region was involved. In conclusion, HGF and TGF-beta transmit the signals through JNK-mediated R-Smads phosphorylation at linker regions.

Pin1 promotes transforming growth factor-beta-induced migration and invasion.

PubMed

Matsuura, Isao; Chiang, Keng-Nan; Lai, Chen-Yu; He, Dongming; Wang, Guannan; Ramkumar, Romila; Uchida, Takafumi; Ryo, Akihide; Lu, Kunping; Liu, Fang

2010-01-15

Transforming growth factor-beta (TGF-beta) regulates a wide variety of biological activities. It induces potent growth-inhibitory responses in normal cells but promotes migration and invasion of cancer cells. Smads mediate the TGF-beta responses. TGF-beta binding to the cell surface receptors leads to the phosphorylation of Smad2/3 in their C terminus as well as in the proline-rich linker region. The serine/threonine phosphorylation sites in the linker region are followed by the proline residue. Pin1, a peptidyl-prolyl cis/trans isomerase, recognizes phosphorylated serine/threonine-proline motifs. Here we show that Smad2/3 interacts with Pin1 in a TGF-beta-dependent manner. We further show that the phosphorylated threonine 179-proline motif in the Smad3 linker region is the major binding site for Pin1. Although epidermal growth factor also induces phosphorylation of threonine 179 and other residues in the Smad3 linker region the same as TGF-beta, Pin1 is unable to bind to the epidermal growth factor-stimulated Smad3. Further analysis suggests that phosphorylation of Smad3 in the C terminus is necessary for the interaction with Pin1. Depletion of Pin1 by small hairpin RNA does not significantly affect TGF-beta-induced growth-inhibitory responses and a number of TGF-beta/Smad target genes analyzed. In contrast, knockdown of Pin1 in human PC3 prostate cancer cells strongly inhibited TGF-beta-mediated migration and invasion. Accordingly, TGF-beta induction of N-cadherin, which plays an important role in migration and invasion, is markedly reduced when Pin1 is depleted in PC3 cells. Because Pin1 is overexpressed in many cancers, our findings highlight the importance of Pin1 in TGF-beta-induced migration and invasion of cancer cells.

Interactions of Plakoglobin and [beta]-Catenin with Desmosomal Cadherins BASIS OF SELECTIVE EXCLUSION OF [alpha]- AND [beta]-CATENIN FROM DESMOSOMES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Hee-Jung; Gross, Julia C.; Pokutta, Sabine

2009-11-18

Plakoglobin and {beta}-catenin are homologous armadillo repeat proteins found in adherens junctions, where they interact with the cytoplasmic domain of classical cadherins and with {alpha}-catenin. Plakoglobin, but normally not {beta}-catenin, is also a structural constituent of desmosomes, where it binds to the cytoplasmic domains of the desmosomal cadherins, desmogleins and desmocollins. Here, we report structural, biophysical, and biochemical studies aimed at understanding the molecular basis of selective exclusion of {beta}-catenin and {alpha}-catenin from desmosomes. The crystal structure of the plakoglobin armadillo domain bound to phosphorylated E-cadherin shows virtually identical interactions to those observed between {beta}-catenin and E-cadherin. Trypsin sensitivity experimentsmore » indicate that the plakoglobin arm domain by itself is more flexible than that of {beta}-catenin. Binding of plakoglobin and {beta}-catenin to the intracellular regions of E-cadherin, desmoglein1, and desmocollin1 was measured by isothermal titration calorimetry. Plakoglobin and {beta}-catenin bind strongly and with similar thermodynamic parameters to E-cadherin. In contrast, {beta}-catenin binds to desmoglein-1 more weakly than does plakoglobin. {beta}-Catenin and plakoglobin bind with similar weak affinities to desmocollin-1. Full affinity binding of desmoglein-1 requires sequences C-terminal to the region homologous to the catenin-binding domain of classical cadherins. Although pulldown assays suggest that the presence of N- and C-terminal {beta}-catenin 'tails' that flank the armadillo repeat region reduces the affinity for desmosomal cadherins, calorimetric measurements show no significant effects of the tails on binding to the cadherins. Using purified proteins, we show that desmosomal cadherins and {alpha}-catenin compete directly for binding to plakoglobin, consistent with the absence of {alpha}-catenin in desmosomes.« less

Effects of propranolol and pindolol on plasma ANP levels in humans at rest and during exercise.

PubMed

Bouissou, P; Galen, F X; Richalet, J P; Lartigue, M; Devaux, F; Dubray, C; Atlan, G

1989-08-01

In attempt to elucidate whether the beta-adrenoceptor is involved in the control of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP level was measured at rest, in recumbent and upright positions, and during graded maximal ergocycle exercise in nine healthy male subjects (23 +/- 0.5 years of age) treated for 3 days with nonselective beta-blockers propranolol (150 mg/day) or pindolol (15 mg/day) or with placebo. The effects of beta-blockers, which differ by their hemodynamic actions at rest because of the intrinsic sympathomimetic activity of pindolol, were compared. Maximal O2 consumption (VO2max) during beta-blockade was not significantly different from the placebo value. Resting heart rate was not affected by pindolol treatment but was decreased with propranolol (-10 beats/min). Both beta-blockers caused a reduction in heart rate at all the exercise intensities. Mean blood pressure was not affected by beta-blockade at rest but was significantly reduced during exercise. During placebo treatment, plasma ANP increased in response to exercise intensities greater than 65% of VO2max. At 100% VO2max plasma ANP was nearly doubled (101.5 +/- 14 pg/ml) compared with the basal value in upright position (56.6 +/- 15 pg/ml). beta-Blockade caused a marked elevation in plasma ANP at all the levels of activity. Despite different hemodynamic responses to pindolol and propranolol, both beta-blockers produced similar increases in the basal level of plasma ANP. These rises were maintained in the course of exercise tests, and no significant difference was found between propranolol and pindolol. We conclude that beta-adrenoceptor mechanisms are not directly responsible for tonic and exercise-induced ANP secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Safe cervical spine clearance in adult obtunded blunt trauma patients on the basis of a normal multidetector CT scan--a meta-analysis and cohort study.

PubMed

Raza, Mushahid; Elkhodair, Samer; Zaheer, Asif; Yousaf, Sohail

2013-11-01

A true gold standard to rule out a significant cervical spine injury in subset of blunt trauma patients with altered sensorium is still to be agreed upon. The objective of this study is to determine whether in obtunded adult patients with blunt trauma, a clinically significant injury to the cervical spine be ruled out on the basis of a normal multidetector cervical spine computed tomography. Comprehensive database search was conducted to include all the prospective and retrospective studies on blunt trauma patients with altered sensorium undergoing cervical spine multidetector CT scan as core imaging modality to "clear" the cervical spine. The studies used two main gold standards, magnetic resonance imaging of the cervical spine and/or prolonged clinical follow-up. The data was extracted to report true positive, true negatives, false positives and false negatives. Meta-analysis of sensitivity, specificity, negative and positive predictive values was performed using Meta Analyst Beta 3.13 software. We also performed a retrospective investigation comparing a robust clinical follow-up and/or cervical spine MR findings in 53 obtunded blunt trauma patients, who previously had undergone a normal multidetector CT scan of the cervical spine reported by a radiologist. A total of 10 studies involving 1850 obtunded blunt trauma patients with initial cervical spine CT scan reported as normal were included in the final meta-analysis. The cumulative negative predictive value and specificity of cervical spine CT of the ten studies was 99.7% (99.4-99.9%, 95% confidence interval). The positive predictive value and sensitivity was 93.7% (84.0-97.7%, 95% confidence interval). In the retrospective review of our obtunded blunt trauma patients, none was later diagnosed to have significant cervical spine injury that required a change in clinical management. In a blunt trauma patient with altered sensorium, a normal cervical spine CT scan is conclusive to safely rule out a clinically significant cervical spine injury. The results of this meta-analysis strongly support the removal of cervical precautions in obtunded blunt trauma patient after normal cervical spine computed tomography. Any further imaging like magnetic resonance imaging of the cervical spine should be performed on case-to-case basis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Infrared spectroscopy and surface chemistry of beta-Ga(2)O(3) nanoribbons.

PubMed

Bermudez, V M; Prokes, S M

2007-12-04

The structure and surface chemistry of crystalline beta-Ga2O3 nanoribbons (NRs), deposited in a thin layer on various metallic and dielectric substrates (mainly on Au), have been characterized using vibrational spectroscopy. The results have been analyzed with the aid of a previous ab initio theoretical model for the beta-Ga2O3 surface structure. Raman spectra and normal-incidence infrared (IR) transmission data show little if any difference from corresponding results for bulk single crystals. For a layer formed on a metallic substrate, IR reflection-absorption spectroscopy (IRRAS) shows longitudinal-optic (LO) modes that are red-shifted by approximately 37 cm-1 relative to those of a bulk crystal. Evidence is also seen for a bonding interaction at the Ga2O3/Au interface following heating in room air. Polarization-modulated IRRAS has been used to study the adsorption of pyridine under steady-state conditions in ambient pressures as high as approximately 5 Torr. The characteristic nu19b and nu8a modes of adsorbed pyridine exhibit little or no shift from the corresponding gas-phase values. This indicates that the surface is only weakly acidic, consistent with the theoretical prediction that singly unsaturated octahedral Ga sites are the only reactive cation sites on the NR surface. However, evidence for adsorption at defect sites is seen in the form of more strongly shifted modes that saturate in intensity at low pyridine coverage. The effect of H atoms, formed by thermal cracking of H2, has also been studied. No Ga-H or O-H bonds are observed on the pristine NR surface. This suggests that the previously reported presence of such species on Ga2O3 powders heated in H2 is a result of a partial reduction of the oxide surface. The heat of adsorption of atomic H on the pristine beta-Ga2O3(100) surface at 0 K is computed to be -1.79 eV per H at saturation (average of Ga-H and O-H sites), whereas a value of +0.45 eV per H is found for the dissociative adsorption of H2. This suggests that rapid recombinative desorption of H2 may limit the coverage of chemisorbed H on this surface.

Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs.

PubMed

Xiao, Y; Smith, R D; Caruso, F S; Kellar, K J

2001-10-01

The opioid agonist properties of (+/-)-methadone are ascribed almost entirely to the (-)-methadone enantiomer. To extend our knowledge of the pharmacological actions of methadone at ligand-gated ion channels, we investigated the effects of the two enantiomers of methadone and its metabolites R-(+)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium perchlorate (EDDP) and R-(+)-2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline hydrochloride (EMDP), as well as structural analogs of methadone, including (-)-alpha-acetylmethadol hydrochloride (LAAM) and (+)-alpha-propoxyphene, on rat alpha3beta4 neuronal nicotinic acetylcholine receptors (nAChRs) stably expressed in a human embryonic kidney 293 cell line, designated KXalpha3beta4R2. (+/-)-methadone inhibited nicotine-stimulated 86Rb+ efflux from the cells in a concentration-dependent manner with an IC50 value of 1.9 +/- 0.2 microM, indicating that it is a potent nAChR antagonist. The (-)- and (+)-enantiomers of methadone have similar inhibitory potencies on nicotine-stimulated 86Rb+ efflux, with IC50 values of approximately 2 microM. EDDP, the major metabolite of methadone, is even more potent, with an IC50 value of approximately 0.5 microM, making it one of the most potent nicotinic receptor blockers reported. In the presence of (+/-)-methadone, EDDP, or LAAM, the maximum nicotine-stimulated 86Rb+ efflux was markedly decreased, but the EC50 value for nicotine stimulation was altered only slightly, if at all, indicating that these compounds block alpha3beta4 nicotinic receptor function by a noncompetitive mechanism. Consistent with a noncompetitive mechanism, (+/-)-methadone, its metabolites, and structural analogs have very low affinity for nicotinic receptor agonist binding sites in membrane homogenates from KXalpha3beta4R2 cells. We conclude that both enantiomers of methadone and its metabolites as well as LAAM and (+)-alpha-propoxyphene are potent noncompetitive antagonists of alpha3beta4 nAChRs.

Screening of beta-glucan contents in commercially cultivated and wild growing mushrooms.

PubMed

Sari, Miriam; Prange, Alexander; Lelley, Jan I; Hambitzer, Reinhard

2017-02-01

Mushrooms have unique sensory properties and nutritional values as well as health benefits due to their bioactive compounds, especially beta-glucans. Well-known edible and medicinal mushroom species as well as uncommon or unknown species representing interesting sources of bioactive beta-glucans have been widely studied. Commercially cultivated and wild growing mushrooms were analysed for their beta-glucan contents. Enzymatic determinations of all glucans, alpha-glucans and beta-glucans in 39 mushrooms species were performed, leading to very remarkable results. Many wild growing species present high beta-glucan contents, especially Bracket fungi. The well-known cultivated species Agaricus bisporus, Lentinula edodes and Cantharellus cibarius as well as most screened wild growing species show higher glucan contents in their stipes than caps. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cooperative alpha-helix formation of beta-lactoglobulin induced by sodium n-alkyl sulfates.

PubMed

Chamani, J; Moosavi-Movahedi, A A; Rajabi, O; Gharanfoli, M; Momen-Heravi, M; Hakimelahi, G H; Neamati-Baghsiah, A; Varasteh, A R

2006-01-01

It is generally assumed that folding intermediates contain partially formed native-like secondary structures. However, if we consider the fact that the conformational stability of the intermediate state is simpler than that of the native state, it would be expected that the secondary structures in a folding intermediate would not necessarily be similar to those of the native state. beta-Lactoglobulin is a predominantly beta-sheet protein, although it has a markedly high intrinsic preference for alpha-helical structure. The formation of non-native alpha-helical intermediate of beta-lactoglobulin was induced by n-alkyl sulfates including sodium octyl sulfate, SOS; sodium decyl sulfate, SDeS; sodium dodecyl sulfate, SDS; and sodium tetradecyl sulfate, STS at special condition. The effect of n-alkyl sulfates on the structure of native beta-lactoglobulin at pH 2 was utilized to investigate the contribution of hydrophobic interactions to the stability of non-native alpha-helical intermediate. The addition of various concentrations of n-alkyl sulfates to the native state of beta-lactoglobulin (pH 2) appears to support the stabilized form of non-native alpha-helical intermediate at pH 2. The m values of the intermediate state of beta-lactoglobulin by SOS, SDeS, SDS and STS showed substantial variation. The enhancement of m values as the stability criterion of non-native alpha-helical intermediate state corresponded with increasing chain length of the cited n-alkyl sulfates. The present results suggest that the folding reaction of beta-lactoglobulin follows a non-hierarchical mechanism and hydrophobic interactions play important roles in stabilizing the non-native alpha-helical intermediate state.

Effects of first postpartum progesterone rise, metabolites, milk yield, and body condition score on the subsequent ovarian activity and fertility in lactating Holstein dairy cows.

PubMed

Kafi, Mojtaba; Mirzaei, Abdolah

2010-04-01

Seventy multiparous healthy lactating Holstein cows (fat-corrected milk yield = 7,561.8 kg) were monitored from 14 days before to 70 days after calving. Transrectal ultrasound scanning was performed twice weekly from 7 to 65 days postpartum. Blood samples were also collected twice weekly to measure serum P(4) and biweekly to detect serum beta-hydroxybutyrate (betaHB) and nonesterified fatty acid (NEFA) concentrations. Body condition score (BCS) was taken biweekly after calving. Based on the serum P(4) profile of 59 cows (11 cows were excluded due to the occurrence of postpartum diseases) studied, 27 (45.8%) had normal ovarian activity, while 21 (35.6%), six (10.1%), three (5.1%), and two (3.4%) had delayed ovulation (DOV), prolonged luteal phase (PLP), short luteal phase (SLP), and cessation of ovarian activity, respectively. Cows with PLP had an earlier ovulation compared to that of cows with normal ovarian activity (23.16 +/- 4.02 vs 31.9 +/- 8.35 days; P < 0.05). PLP cows also had a greater mean +/- standard deviation peak milk yield (44.2 +/- 5.8 vs 37.2 +/- 5.7 kg/day, 75 days postpartum; P < 0.05) than cows with normal postpartum ovarian activity. The PLP group also had greater milk production in the previous lactation period. Logistic regression analysis indicated that cows with P(4) concentration > or =1 ng/ml on day 24 after calving were more at risk for PLP by 1.1 for each 1 kg increase in mean peak milk yield during 75 days after calving. BCS was lower in cows with DOV compared to that of cows with normal ovarian activity at any time after calving (P < 0.05). Serum betaHB concentrations in DOV cows were significantly higher than that of normal cows on day 42 after calving (0.69 +/- 0.29 vs 0.54 +/- 0.12 mmol/L, P < 0.05). No significant difference was found in the mean concentrations of NEFA between cows in different groups at any time after calving (P > 0.05). The concentrations of P(4) on days 28 and 31 were negatively correlated with betaHB concentration on day 42 after calving in cows with normal ovarian activity (R = -0.44, P = 0.02). In conclusion, these findings suggest that early ovulation and hence early postpartum P(4) rise in addition to the high milk production could partly be responsible for the occurrence of PLP in dairy cows.

A survey of the kinetic parameters of class C beta-lactamases. Penicillins.

PubMed Central

Galleni, M; Frère, J M

1988-01-01

The interaction between six class C beta-lactamases and various penicillins has been studied. All the enzymes behaved in a very uniform manner. Benzylpenicillin exhibited relatively low kcat. values (14-75 s-1) but low values of Km resulted in high catalytic efficiencies [kcat./Km = 10 X 10(6)-75 X 10(6) M-1.s-1]. The kcat. values for ampicillin were 10-100-fold lower. Carbenicillin, oxacillin cloxacillin and methicillin were very poor substrates, exhibiting kcat. values between 1 x 10(-3) and 0.1 s-1. The Km values were correspondingly small. It could safely be hypothesized that, with all the tested substrates, deacylation was rate-limiting, resulting in acyl-enzyme accumulation. PMID:3264154

Guinea-pig liver testosterone 17 beta-dehydrogenase (NADP+) and aldehyde reductase exhibit benzene dihydrodiol dehydrogenase activity.

PubMed Central

Hara, A; Hayashibara, M; Nakayama, T; Hasebe, K; Usui, S; Sawada, H

1985-01-01

We have kinetically and immunologically demonstrated that testosterone 17 beta-dehydrogenase (NADP+) isoenzymes (EC 1.1.1.64) and aldehyde reductase (EC 1.1.1.2) from guinea-pig liver catalyse the oxidation of benzene dihydrodiol (trans-1,2-dihydroxycyclohexa-3,5-diene) to catechol. One isoenzyme of testosterone 17 beta-dehydrogenase, which has specificity for 5 beta-androstanes, oxidized benzene dihydrodiol at a 3-fold higher rate than 5 beta-dihydrotestosterone, and showed a more than 4-fold higher affinity for benzene dihydrodiol and Vmax. value than did another isoenzyme, which exhibits specificity for 5 alpha-androstanes, and aldehyde reductase. Immunoprecipitation of guinea-pig liver cytosol with antisera against the testosterone 17 beta-dehydrogenase isoenzymes and aldehyde reductase indicated that most of the benzene dihydrodiol dehydrogenase activity in the tissue is due to testosterone 17 beta-dehydrogenase. PMID:2983661

[BiOBr promoted the photocatalytic degradation of beta-cypermethrin under visible light].

PubMed

Peng, Yi-Zhu; Zhao, Xiao-Rong; Jia, Man-Ke; Zhou, Wei; Huang, Ying-Ping

2014-05-01

As a visible light photocatalyst, bismuth oxide bromide (BiOBr) was used to catalyze the degradation of beta-cypermethrin (beta-CP). The photocatalytic degradation of beta-CP was studied with gas chromatography. The effects of pH and catalyst dose on the photocatalytic degradation efficiency were discussed. The oxidization and mineralization of beta-CP were detected by chemical oxygen demand (COD) analyzer. The results showed that beta-CP could be effectively degraded under visible light irradiation using BiOBr as the catalyst. At given experimental conditions, the degradation rate of beta-CP reached 94. 68% after 10 h and the COD removal rate reached 67. 99% after 36 h. With the increase of catalyst dose and pH value, the degradation rate was improved. The photocatalytic oxidation species was determined by peroxidase method and terephthalic acid fluorescence method. These results suggested that the photocatalytic degradation process mainly referred to hydroxyl radical ( OH) mechanism.

Mathematical beta function formulation for maxillary arch form prediction in normal occlusion population.

PubMed

Mina, Morteza; Borzabadi-Farahani, Ali; Tehranchi, Azita; Nouri, Mahtab; Younessian, Farnaz

2017-04-01

The aim of this study was to assess the dental arch curvature in subjects with normal occlusion in an Iranian population and propose a beta function formula to predict maxillary arch form using the mandibular intermolar widths (IMW) and intermolar depths (IMD). The materials used were study casts of 54 adolescents with normal occlusion and mean age of 14.1 years (25 males, 29 females, age range 12-16 years). Curve-fitting analyses were carried out and the curves passing through the facial-axis point of the canines, premolars, first molars, and the incisal edges of the anterior teeth were studied using a 3D laser scanner. Using the measured IMW and IMD of the dental arches at the maxillary and mandibular first molar region, a beta function formula proposed for predicting maxillary arch form. The accuracy of the proposed formula was assessed on 10 randomly selected dental casts. The mean (SD) of the maxillary and mandibular IMW and IMD were 57.92 (4.75), 54.19 (5.31), and 31.59 (2.90) and 28.10 (2.59) mm, respectively. There was no gender dimorphism (P > 0.05) for both variables (IMW, IMD). There was a strong positive association (n = 10, Pearson r = 0.98, P < 0.05) between the measured (actual) maxillary arch length and proposed arch length derived from generated formula. The goodness of fit (whole arch) for the proposed beta function formula, using adjusted r square measure and root mean square in 10 patients averaged 0.97 and 1.49 mm, respectively. The corresponding figures for the maxillary anterior arch (canine to canine) were 0.90 and 0.92 mm, respectively. The proposed beta function formula used for predicting maxillary arch form based on two mandibular measures (IMW, IMD) was found to have a high accuracy for maxillary arch prediction in the Iranian population and may be used as a guide to fabricate customized arch wires or as an aid in maxillary reconstructive surgery.

Insulin-like growth factor I in inclusion-body myositis and human muscle cultures.

PubMed

Broccolini, Aldobrando; Ricci, Enzo; Pescatori, Mario; Papacci, Manuela; Gliubizzi, Carla; D'Amico, Adele; Servidei, Serenella; Tonali, Pietro; Mirabella, Massimiliano

2004-06-01

Possible pathogenic mechanisms of sporadic inclusion-body myositis (sIBM) include abnormal production and accumulation of amyloid beta (A beta), muscle aging, and increased oxidative stress. Insulin-like growth factor I (IGF-I), an endocrine and autocrine/paracrine trophic factor, provides resistance against A beta toxicity and oxidative stress in vitro and promotes cell survival. In this study we analyzed the IGF-I signaling pathway in sIBM muscle and found that 16.2% +/- 2.5% of nonregenerating fibers showed increased expression of IGF-I, phosphatidylinositide 3'OH-kinase, and Akt. In the majority of sIBM abnormal muscle fibers, increased IGF-I mRNA and protein correlated with the presence of A beta cytoplasmic inclusions. To investigate a possible relationship between A beta toxicity and IGF-I upregulation, normal primary muscle cultures were stimulated for 24 hours with the A beta(25-35) peptide corresponding to the biologically active domain of A beta. This induced an increase of IGF-I mRNA and protein in myotubes at 6 hours, followed by a gradual reduction thereafter. The level of phosphorylated Akt showed similar changes. We suggest that in sIBM. IGF-I overexpression represents a reactive response to A beta toxicity, possibly providing trophic support to vulnerable fibers. Understanding the signaling pathways activated by IGF-I in sIBM may lead to novel therapeutic strategies for the disease.

First Compilation and Evaluation of Beta-Delayed Neutron Emission Probabilities and Associated Half-Lives for A ≤72 Nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Birch, M.; Singh, B.; Abriola, D.

2014-06-01

After a comprehensive compilation and evaluation of beta-delayed neutron (β -n) emission probabilities, P n, and associated half-lives for A ≤ 72 nuclei has been performed for the first time. The recommended values have been used to analyze the systematics of β -nemission in this region. The ratio P n/T 1/2 is better correlated with the Q-value of the β -n decay mode than the previously proposed Kratz-Herrmann Formula (KHF). Moreover, the recommended values are also compared with theoretical quasi-particle random phase approximation (QRPA) calculations.

Determination of carotenoids in foods by high-performance liquid chromatography.

PubMed

Abdel-Kader, Z M

1991-01-01

The mean values of alpha and beta-carotene of 10 fruits and vegetables from supermarkets in Cairo and Alexandria have been determined using HPLC method, and the average vitamin A activities (in retinol equivalents) calculated. Carrots, spinach and sweet potatoes were the best sources of provitamin A activity. Beta-carotene was the more prevalent carotenoid compared with alpha-carotene. An analysis of variance including all foods investigated demonstrated that there were no significant differences among either locations or times of analysis. There was no difference between the analysed values of vitamin A activity and the USDA Handbook No. 8 values.

Identification of some important metabolites of boldenone in urine and feces of cattle by gas chromatography-mass spectrometry.

PubMed

Van Puymbroeck, M; Kuilman, M E; Maas, R F; Witkamp, R F; Leyssens, L; Vanderzande, D; Gelan, J; Raus, J

1998-12-01

17 alpha-Boldenone (17 alpha-BOL) and/or 17 beta-boldenone (17 beta-BOL) appear occasionally in fecal matter of cattle. In addition to 17 alpha-BOL, a whole array of boldenone related substances can be found in the same samples. In vitro experiments with microsomal liver preparations and isolated hepatocytes combined with the excretion profiles found in urine and feces samples of in vivo experiments made it possible to identify several metabolites of 17 beta-BOL in 17 beta-BOL positive feces samples. In one animal treated with 17 beta-BOL, no 17 beta-BOL or its metabolites were present before treatment and most of these compounds disappeared gradually in time after the treatment was stopped. It is not clear what the origin is of 17 alpha-BOL and boldenone metabolites in samples screened routinely for the abuse of anabolic steroids and considered to be 'negative' because of the absence of 17 beta-BOL since other workers showed some evidence that 17 alpha-BOL can be of endogenous origin. However, in our hands, most of these 17 alpha-BOL positive samples, obtained during routinely performed screenings of cattle, contained large amounts of delta 4-androstene-3,17-dione (AED), which normally is absent from routinely screened negative samples. Furthermore, AED was absent in all samples obtained from the animals treated with 17 beta-BOL. We have no direct evidence that 17 alpha-BOL or 17 beta-BOL is of endogenous origin.

MafK/NF-E2 p18 is required for beta-globin genes activation by mediating the proximity of LCR and active beta-globin genes in MEL cell line.

PubMed

Du, Mei-Jun; Lv, Xiang; Hao, De-Long; Zhao, Guo-Wei; Wu, Xue-Song; Wu, Feng; Liu, De-Pei; Liang, Chih-Chuan

2008-01-01

Evidences indicate that locus control region (LCR) of beta-globin spatially closes to the downstream active gene promoter to mediate the transcriptional activation by looping. DNA binding proteins may play an important role in the looping formation. NF-E2 is one of the key transcription factors in beta-globin gene transcriptional activation. To shed light on whether NF-E2 is involved in this process, DS19MafKsiRNA cell pools were established by specifically knocked down the expression of MafK/NF-E2 p18, one subunit of NF-E2 heterodimer. In the above cell pools, it was observed that the occupancy efficiency of NF-E2 on beta-globin gene locus and the expression level of beta-globin genes were decreased. H3 acetylation, H3-K4 methylation and the deposition of RNA polymerase II, but not the recruitment of GATA-1, were also found reduced at the beta-globin gene cluster. Chromosome Conformation Capture (3C) assay showed that the cross-linking frequency between the main NF-E2 binding site HS2 and downstream structural genes was reduced compared to the normal cell. This result demonstrated that MafK/NF-E2 p18 recruitment was involved in the physical proximity of LCR and active beta-globin genes upon beta-globin gene transcriptional activation.

Developing injectable immunoglobulins to treat cognitive impairment in Alzheimer's disease.

PubMed

Steinitz, Michael

2008-05-01

Alzheimer's disease is a devastating disorder, clinically characterized by a comprehensive cognitive decline. The novel strategy of anti-amyloid-beta immunotherapy has been suggested following encouraging results obtained in murine models of Alzheimer's disease, in non-human primates, and in small-scale clinical trials. To examine the choice between active or passive anti-amyloid-beta immunization and the choice of the molecule to which the immune machinery should be targeted, which are central issues in future immune therapy of Alzheimer's disease. Research into the new area of Alzheimer's disease immune therapy is primarily based on in vivo and in vitro studies of murine models of Alzheimer's disease. The studies are hence limited to defined genetic deficiencies. In humans, infusion of anti-amyloid-beta antibodies is considered a safer approach than active anti-amyloid-beta vaccination. Alzheimer's-disease-protective anti-amyloid-beta monoclonal antibodies should target specific epitopes within the amyloid beta(1 42) peptide, avoiding possibly harmful binding to the ubiquitous normal amyloid precursor protein. Since Alzheimer's disease immunotherapy requires repeated infusion of antibodies over a prolonged period of time, Alzheimer's disease patients will tolerate such antibodies provided the latter are exclusively of human origin. Human monoclonal antibodies that correspond to ubiquitous anti-amyloid-beta, present in all healthy humans, might bear important protective characteristics.

Effect of metoprolol on the beta-adrenoceptor density of lymphocytes in patients with dilated cardiomyopathy.

PubMed

Ishida, S; Makino, N; Masutomo, K; Hata, T; Yanaga, T

1993-05-01

We investigated the effect of the beta 1-selective blocker metoprolol on the beta-adrenergic receptor density of circulating lymphocytes in patients with dilated cardiomyopathy. Nine men in New York Heart Association functional classes II (six patients) and III were given metoprolol for 6 months (mean dose 45.6 +/- 18.1 mg). Their cardiac function was assessed by echocardiography. Although there was no difference in the heart rate or pressure rate products, the end-systolic and end-diastolic dimensions significantly decreased in six patients after metoprolol treatment. The ejection fraction, fractional shortening, and mean left ventricular circumferential shortening were significantly increased after the treatment. beta-Adrenoceptor densities of lymphocytes, examined by iodine 125-labeled iodocyanopindolol, were reduced in patients at entry but recovered to normal levels after the metoprolol treatment. The dissociation constants did not differ at any stage of the disease. The relationship between beta-adrenoceptor densities in lymphocytes and echocardiographic parameters showed a positive correlation with the plasma norepinephrine concentration. This study thus provides evidence that long-term metoprolol therapy for dilated cardiomyopathy is associated with beta-receptor up-regulation, and the restoration of myocardial beta-receptor density may be associated with the improved cardiac function as determined by echocardiography.

Induction of myofibroblastic differentiation in vitro by covalently immobilized transforming growth factor-beta(1).

PubMed

Metzger, Wolfgang; Grenner, Nadine; Motsch, Sandra E; Strehlow, Rothin; Pohlemann, Tim; Oberringer, Martin

2007-11-01

Growth factors are an important tool in tissue engineering. Bone morphogenetic protein-2 and transforming growth factor-beta(1) (TGF-beta(1)) are used to provide bioactivity to surgical implants and tissue substitute materials. Mostly growth factors are used in soluble or adsorbed form. However, simple adsorption of proteins to surfaces is always accompanied by reduced stability and undefined pharmacokinetics. This study aims to prove that TGF-beta(1) can be covalently immobilized to functionalized surfaces, maintaining its ability to induce myofibroblastic differentiation of normal human dermal fibroblasts. In vivo, fibroblasts differentiate to myofibroblasts (MFs) during soft tissue healing by the action of TGF-beta(1). As surfaces for our experiments, we used slides bearing aldehyde, epoxy, or amino groups. For our in vitro cell culture experiments, we used the expression of alpha-smooth muscle actin as a marker for MFs after immunochemical staining. Using the aldehyde and the epoxy slides, we were able to demonstrate the activity of immobilized TGF-beta(1) through a significant increase in MF differentiation rate. A simple immunological test was established to detect TGF-beta(1) on the surfaces. This technology enables the creation of molecular "landscapes" consisting of several factors arranged in a distinct spatial pattern and immobilized on appropriate surfaces.

What is beta-carotene doing in the photosystem II reaction centre?

PubMed Central

Telfer, Alison

2002-01-01

During photosynthesis carotenoids normally serve as antenna pigments, transferring singlet excitation energy to chlorophyll, and preventing singlet oxygen production from chlorophyll triplet states, by rapid spin exchange and decay of the carotenoid triplet to the ground state. The presence of two beta-carotene molecules in the photosystem II reaction centre (RC) now seems well established, but they do not quench the triplet state of the primary electron-donor chlorophylls, which are known as P(680). The beta-carotenes cannot be close enough to P(680) for triplet quenching because that would also allow extremely fast electron transfer from beta-carotene to P(+)(680), preventing the oxidation of water. Their transfer of excitation energy to chlorophyll, though not very efficient, indicates close proximity to the chlorophylls ligated by histidine 118 towards the periphery of the two main RC polypeptides. The primary function of the beta-carotenes is probably the quenching of singlet oxygen produced after charge recombination to the triplet state of P(680). Only when electron donation from water is disturbed does beta-carotene become oxidized. One beta-carotene can mediate cyclic electron transfer via cytochrome b559. The other is probably destroyed upon oxidation, which might trigger a breakdown of the polypeptide that binds the cofactors that carry out charge separation. PMID:12437882

Agaritine purified from Agaricus blazei Murrill exerts anti-tumor activity against leukemic cells.

PubMed

Endo, Masahiro; Beppu, Hidehiko; Akiyama, Hidehiko; Wakamatsu, Kazumasa; Ito, Shosuke; Kawamoto, Yasuko; Shimpo, Kan; Sumiya, Toshimitu; Koike, Takaaki; Matsui, Taei

2010-07-01

Mushrooms of the genus Agaricus are a common folk remedy against carcinoma. The active ingredients, polysaccharides and protein-polysaccharide complexes containing beta-glucan, have been isolated and shown to have indirect tumor-suppressing activity via an immunological activation. The diffusible fraction of a hot-water extract of Agaricus blazei Murrill (ABM) powder was fractionated by HPLC based on the anti-tumor activity against leukemic cells in vitro. The structure of the anti-tumor substance was determined by NMR and MS analyses. We purified a tumorcidal substance from the diffusible fraction of ABM and identified it as agaritine, beta-N-(gamma-l(+)-glutamyl)-4-(hydroxymethyl) phenylhydrazine, having a molecular mass of 267 Da. This compound inhibited the proliferation of leukemic cell lines such as U937, MOLT4, HL60 and K562 with IC(50) values of 2.7, 9.4, 13.0, and 16.0 microg/mL, respectively, but showed no significant effect on normal lymphatic cells at concentrations up to 40 microg/mL. Although agaritine has been suspected of having genotoxic or carcinogenic properties, agaritine did not activate the umu gene of Salmonella, which reacts to carcinogens. The results indicate that agaritine from ABM has direct anti-tumor activity against leukemic tumor cells in vitro. This is in contrast to the carcinogenic activity previously ascribed to this compound. Our results also show that this activity is distinct from that of beta-glucan, which indirectly suppresses proliferation of tumor cells. Copyright 2010 Elsevier B.V. All rights reserved.

Method for Phenotypic Detection of Extended-Spectrum Beta-Lactamases in Enterobacter Species in the Routine Clinical Setting ▿

PubMed Central

Stuart, James Cohen; Diederen, Bram; al Naiemi, Nashwan; Fluit, Ad; Arents, Niek; Thijsen, Steven; Vlaminckx, Bart; Mouton, Johan W.; Leverstein-van Hall, Maurine

2011-01-01

In 271 Enterobacter blood culture isolates from 12 hospitals, extended-spectrum beta-lactamase (ESBL) prevalence varied between 0% and 30% per hospital. High prevalence was associated with dissemination, indicating the potential relevance of infection control measures. Screening with cefepime or Vitek 2, followed by a cefepime/cefepime-clavulanate Etest, was an accurate strategy for ESBL detection in Enterobacter isolates (positive predictive value, 100%; negative predictive value, 99%). PMID:21562100

Epstein-Barr virus associated modulation of Wnt pathway is not dependent on latent membrane protein-1.

PubMed

Webb, Natasha; Connolly, Geoff; Tellam, Judy; Yap, Alpha S; Khanna, Rajiv

2008-09-22

Previous studies have indicated that Epstein-Barr virus (EBV) can modulate the Wnt pathway in virus-infected cells and this effect is mediated by EBV-encoded oncogene latent membrane protein 1 (LMP1). Here we have reassessed the role of LMP1 in regulating the expression of various mediators of the canonical Wnt cascade. Contradicting the previous finding, we found that the levels of E-cadherin, beta-catenin, Glycogen Synthase Kinase 3ss (GSK3beta), axin and alpha-catenin were not affected by the expression of LMP1 sequences from normal B cells or nasopharyngeal carcinoma. Moreover, we also show that LMP1 expression had no detectable effect on the E-cadherin and beta-catenin interaction and did not induce transcriptional activation of beta-catenin. Taken together these studies demonstrate that EBV-mediated activation of Wnt pathway is not dependent on the expression of LMP1.

Zinc-Amyloid Interactions on a Millisecond Time-Scale Stabilize Non-Fibrillar Alzheimer Related Species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noy,D.; Solomonov, I.; Sinkevich, O.

2008-01-01

The role of zinc, an essential element for normal brain function, in the pathology of Alzheimer's disease (AD) is poorly understood. On one hand, physiological and genetic evidence from transgenic mouse models supports its pathogenic role in promoting the deposition of the amyloid {beta}-protein (A{beta}) in senile plaques. On the other hand, levels of extracellular ('free') zinc in the brain, as inferred by the levels of zinc in cerebrospinal fluid, were found to be too low for inducing A{beta} aggregation. Remarkably, the release of transient high local concentrations of zinc during rapid synaptic events was reported. The role of suchmore » free zinc pulses in promoting A{beta} aggregation has never been established. Using a range of time-resolved structural and spectroscopic techniques, we found that zinc, when introduced in millisecond pulses of micromolar concentrations, immediately interacts with A{beta} 1-40 and promotes its aggregation. These interactions specifically stabilize non-fibrillar pathogenic related aggregate forms and prevent the formation of A{beta} fibrils (more benign species) presumably by interfering with the self-assembly process of A{beta}. These in vitro results strongly suggest a significant role for zinc pulses in A{beta} pathology. We further propose that by interfering with A{beta} self-assembly, which leads to insoluble, non-pathological fibrillar forms, zinc stabilizes transient, harmful amyloid forms. This report argues that zinc represents a class of molecular pathogens that effectively perturb the self-assembly of benign A{beta} fibrils, and stabilize harmful non-fibrillar forms.« less

A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, L.; Sakkal-Alkaddour, S.; Chang, Ying T.

1996-01-01

We report a new compound heterozygous frameshift mutation in the type II 3{Beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) gene in a Pakistanian female child with the salt-wasting form of 3{Beta}-HSD deficiency congenital adrenal hyperplasia. The etiology for her congenital adrenal hyperplasia was not defined. Although the family history suggested possible 3{beta}-HSd deficiency disorder, suppressed adrenal function caused by excess glucocorticoid therapy in this child at 7 yr of age did not allow hormonal diagnosis. To confirm 3{beta}-HSD deficiency, we sequenced the type II 3{beta}-HSD gene in the patient, her family, and the parents of her deceased paternal cousins. The type II 3{beta}-HSD genemore » region of a putative promotor, exons I, II, III, and IV, and exon-intron boundaries were amplified by PCR and sequenced in all subjects. The DNA sequence of the child revealed a single nucleotide deletion at codon 318 [ACA(Thr){r_arrow}AA] in exon IV in one allele, and two nucleotide deletions at codon 273 [AAA(Lys){r_arrow}A] in exon IV in the other allele. The remaining gene sequences were normal. The codon 318 mutation was found in one allele from the father, brother, and parents of the deceased paternal cousins. The codon 273 mutation was found in one allele of the mother and a sister. These findings confirmed inherited 3{beta}-HSD deficiency in the child caused by the compound heterozygous type II 3{beta}-HSD gene mutation. Both codons at codons 279 and 367, respectively, are predicted to result in an altered and truncated type II 3{beta}-HSD protein, thereby causing salt-wasting 3{beta}-HSD deficiency in the patient. 21 refs., 2 figs., 1 tab.« less

25-hydroxyvitamin D in obese youth across the spectrum of glucose tolerance from normal to prediabetes to type 2 diabetes

USDA-ARS?s Scientific Manuscript database

The objective of this study was to 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and Beta-cell ...

Adverse effects of nicotine and interleukin-1beta on autoresuscitation after apnea in piglets: implications for sudden infant death syndrome.

PubMed

Frøen, J F; Akre, H; Stray-Pedersen, B; Saugstad, O D

2000-04-01

Maternal cigarette smoking is established as a major dose-dependent risk factor for sudden infant death syndrome (SIDS). Both prenatal and postnatal exposures to constituents of tobacco smoke are associated with SIDS, but no mechanism of death attributable to nicotine has been found. Breastfeeding gives a substantial increase in absorbed nicotine compared with only environmental tobacco smoke when the mother smokes, because the milk:plasma concentration ratio of nicotine is 2.9 in smoking mothers. Furthermore, many SIDS victims have a slight infection and a triggered immune system before their death, thus experiencing a release of cytokines like interleukin-1beta (IL-1beta) that may depress respiration. Because apneas in infancy are associated with SIDS, we have tested the hypothesis that postnatal exposure to tobacco constituents and infections might adversely affect an infant's ability to cope with an apneic episode. This is performed by investigating the acute effects of nicotine and IL-1beta on apnea by laryngeal reflex stimulation and on the subsequent autoresuscitation. Thirty 1-week-old piglets (+/-1 day) were sedated with azaperone. A tracheal and an arterial catheter were inserted during a short halothane anesthesia. The piglets were allowed a 30-minute stabilization period before baseline values were recorded and they were randomized to 4 pretreatment groups (avoiding siblings in the same group): 1) immediate infusion of 10 pmol IL-1beta intravenously/kg (IL-1beta group; n = 8); 2) slow infusion of 5 microg nicotine intravenously/kg 5 minutes later (NIC group; n = 8); 3) both IL-1beta and NIC combined (NIC + IL-1beta group; n = 6); or 4) placebo by infusion of 1 ml .9% NaCl (CTR group; n = 8). Fifteen minutes later, apnea was induced by insufflation of .1 ml of acidified saline (pH = 2) in the subglottic space 5 times with 5-minute intervals, and variables of respiration, heart rate, blood pressure, and blood gases were recorded. Stimulation of the laryngeal chemoreflex by insufflation of acidified saline in the subglottic space produced apneas, primarily of central origin. This was followed by a decrease in heart rate, a fall in blood pressure, swallowing, occasional coughs, and finally autoresuscitation with gasping followed by rapid increase in heart rate, rise in blood pressure, and (in the CTR group) an increase of respiratory rate. Piglets pretreated with nicotine had more spontaneous apneas, and repeated spontaneous apneas caused an inability to perform a compensatory increase of the respiratory rate after induced apnea. This resulted in a lower SaO(2) than did CTR at 2 minutes after apnea (data shown as median [interquartile range]: 91% [91-94] vs 97% [94-98]). The pretreatment with IL-1beta caused prolonged apneas in piglets and an inability to hyperventilate causing a postapneic respiratory rate similar to the NIC. When nicotine and IL-1beta were combined, additive adverse effects on respiratory control and autoresuscitation compared with CTR were observed: NIC + IL-1beta had significantly more spontaneous apneas the last 5 minutes before induction of apnea (2 [.3-3] vs 0 [0-0]). Apneas were prolonged (46 seconds [39-51] vs 26 seconds [22-31]) and followed by far more spontaneous apneas the following 5 minutes (6.6 [4.0-7.9] vs.5 [.2- .9]). Instead of normal hyperventilation after apnea, a dramatic decrease in respiratory rate was seen (at 20 seconds: -45% [-28 to -53] vs +29% [+24-+50], and at 60 seconds: -27% [-23 to -32] vs +3% [-2-+6), leading to SaO(2) below 90% 3 minutes after end of apnea: 89% (87-93) versus 97% (95-98). These prolonged adverse effects on ventilation were reflected in lowered PaO(2), elevated PaCO(2) and lowered pH 2 minutes, and even 5 minutes, after induction of apnea. Nicotine interferes with normal autoresuscitation after apnea when given in doses within the range of what the child of a smoking mother could receive through environmental t

An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

PubMed

Chronowski, Gregory M; Wilder, Richard B; Tucker, Susan L; Ha, Chul S; Sarris, Andreas H; Hagemeister, Fredrick B; Barista, Ibrahim; Hess, Mark A; Cabanillas, Fernando; Cox, James D

2002-12-15

The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10998

A preliminary path analysis of expectancy and patient-provider encounter in an open-label randomized controlled trial of spinal manipulation for cervicogenic headache.

PubMed

Haas, Mitchell; Aickin, Mikel; Vavrek, Darcy

2010-01-01

The purpose of this article was to present a preliminary model to identify the effects of expectancy of treatment success and the patient-provider encounter (PPE) on outcomes in an open-label randomized trial. Eighty participants with chronic cervicogenic headache (CGH) were randomized to 4 groups: 2 levels of treatment dose (8 or 16) and 2 levels of therapy from a chiropractor (spinal manipulation or light massage). Providers were instructed to have equal enthusiasm for all care. Structural equation modeling with standardized path coefficients (beta) was used in a path analysis to identify the effects of patient expectancy and the PPE on CGH pain. The model included monthly pain from baseline to 12 weeks. Expectancy and PPE were evaluated on Likert scales. The patient-provider encounter was measured as patient perception of chiropractor enthusiasm, confidence, and comfort with care. Baseline patient expectancy was balanced across groups. The PPE measures were balanced across groups and consistent over the 8-week treatment period. Treatment and baseline pain had the strongest effects on pain outcomes (|beta| = .46-.59). Expectations had little effect on pain (abs value(beta) < .15). The patient-provider encounter had a weak effect on pain (abs value(beta)= .03-.27) and on subsequent confidence in treatment success (abs value(beta)= .09 and .12). Encouraging equipoise in the PPE and balancing expectancy across treatment groups may protect against some confounding related to the absence of blinding in a randomized controlled trial of pain. In this trial, their effects were found to be small relative to the effects of treatment and baseline values. Copyright 2010 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

The Roles of TGF-Beta and TGF-Beta Signaling Receptors in Breast Carcinogenesis.

DTIC Science & Technology

1997-07-01

phosphorylation of these molecules in a normal mammary epithelial cell line. Subsequently, we have focused on the functional role of Smad3 and Smad4 as...serine residues in the C-terminal portion of Smadl and Smad2, though the corresponding highly conserved sites in Smad3 and Smad5 most likely serve the...far, it appears that Smad2 and Smad3 , which share 92% sequence identity, are likely mediators for the TGF-B signal, whereas Smadl and Smad5, which

Influence of antibody formation on reduction of globotriaosylceramide (GL-3) in urine from Fabry patients during agalsidase beta therapy.

PubMed

Ohashi, Toya; Sakuma, Mio; Kitagawa, Teruo; Suzuki, Ken; Ishige, Nobuyuki; Eto, Yoshikatsu

2007-11-01

Two recombinant human agalsidase preparations are available for treatment of Fabry disease. We assayed urinary GL-3 (uGL-3) concentration in seronegative and seropositive patients receiving agalsidase beta (1mg/kg). Antibody formation and residual enzyme activity were strongly correlated. Normalization of uGL-3 was achieved more efficiently in seronegatives. But different from previous reports, reduction of uGL-3 level was observed in some seropositive patients.

[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

PubMed

Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

2013-01-01

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

Synthetic Beta-Lactam Antibiotics as a Selective Breast Cancer Cell Apoptosis Inducer: Significance in Breast Cancer Prevention and Treatment

DTIC Science & Technology

2008-03-01

Learned from Diet-Gene-Environment Interaction. Environmental Toxicology Graduate Program and Department of Chemistry , University of California at...College of Chemistry , Central China Normal University, Wuhan, China, June 29, 2007 Dou QP. Invited Speaker. Molecular Prevention of Human Cancer: Role of...Discovery Today 2002; 7: 471-8. 3. Morin RB and Gorman M. Chemistry and Biology of beta-Lactam Antibiotics, Vol. 1-3. New York: Academic Press, 1982. 4

Lymphocyte changes in beta-thalassaemia major.

PubMed Central

Musumeci, S; Schiliro, G; Romeo, M A; Sciotto, A; Rosalba, A; Pizzarelli, G

1979-01-01

Lymphocyte subpopulations were studied in 20 hypertransfused patients with beta-thalassaemia major, some of whom had been splenectomised. B-lymphocytes were normal but T-lymphocytes were decreased in all patients. The T-cell count was lower in the splenectomised patients than in the nonsplenectomised ones. In the former, the active rosette-forming lymphocytes were also diminished, but the difference was not significant. In all patients the percentage of null cells was greater and the activity of K-cells increased compared with controls. PMID:316991

In vitro biosynthesis of galactans by membrane-bound galactosyltransferase from radish ( Raphanus sativus L.) seedlings.

PubMed

Kato, Hideaki; Takeuchi, Yoshimi; Tsumuraya, Yoichi; Hashimoto, Yohichi; Nakano, Hirofumi; Kovác, Pavol

2003-06-01

We investigated a galactosyltransferase (GalT) involved in the synthesis of the carbohydrate portion of arabinogalactan-proteins (AGPs), which consist of a beta-(1-->3)-galactan backbone from which consecutive (1-->6)-linked beta-Gal p residues branch off. A membrane preparation from 6-day-old primary roots of radish ( Raphanus sativus L.) transferred [(14)C]Gal from UDP-[(14)C]Gal onto a beta-(1-->3)-galactan exogenous acceptor. The reaction occurred maximally at pH 5.9-6.3 and 30 degrees C in the presence of 15 mM Mn(2+) and 0.75% Triton X-100. The apparent K(m) and V(max) values for UDP-Gal were 0.41 mM and 1,000 pmol min(-1) (mg protein)(-1), respectively. The reaction with beta-(1-->3)-galactan showed a bi-phasic kinetic character with K(m) values of 0.43 and 2.8 mg ml(-1). beta-(1-->3)-Galactooligomers were good acceptors and enzyme activity increased with increasing polymerization of Gal residues. In contrast, the enzyme was less efficient on beta-(1-->6)-oligomers. The transfer reaction for an AGP from radish mature roots was negligible but could be increased by prior enzymatic or chemical removal of alpha- l-arabinofuranose (alpha- l-Ara f) residues or both alpha- l-Ara f residues and (1-->6)-linked beta-Gal side chains. Digestion of radiolabeled products formed from beta-(1-->3)-galactan and the modified AGP with exo-beta-(1-->3)-galactanase released mainly radioactive beta-(1-->6)-galactobiose, indicating that the transfer of [(14)C]Gal occurred preferentially onto consecutive (1-->3)-linked beta-Gal chains through beta-(1-->6)-linkages, resulting in the formation of single branching points. The enzyme produced mainly a branched tetrasaccharide, Galbeta(1-->3)[Galbeta(1-->6)] Galbeta(1-->3)Gal, from beta-(1-->3)-galactotriose by incubation with UDP-Gal, confirming the preferential formation of the branching linkage. Localization of the GalT in the Golgi apparatus was revealed on a sucrose density gradient. The membrane preparation also incorporated [(14)C]Gal into beta-(1-->4)-galactan, indicating that the membranes contained different types of GalT isoform catalyzing the synthesis of different types of galactosidic linkage.

Studies on the bioavailability of the provitamin A carotenoid, beta-carotene, using human exfoliated colonic epithelial cells.

PubMed

Gireesh, T; Nair, P P; Sudhakaran, P R

2004-08-01

The possibility of using exfoliated colonic epithelial cells for assessing the bioavailability of beta-carotene was examined. Analysis of exfoliated colonic epithelial cells showed the presence of beta-carotene and vitamin A. The beta-carotene content was significantly lower in cells from stool samples of subjects on a beta-carotene-poor diet than those receiving a single dose of a beta-carotene supplement. Colonic epithelial cells isolated from stool samples collected daily during a wash-out period while the subjects were on a beta-carotene-poor diet showed a steady decrease in beta-carotene content, reaching the lowest value on day 7. Kinetic analysis showed that a single dose of a beta-carotene supplement in the form of spirulina (Spirulina platensis) or agathi (Sesbania grandiflora) after the wash-out period caused an increase in the beta-carotene content after a lag period of 5-7 d, but the vitamin A levels during these periods were not significantly affected. Analysis of plasma beta-carotene concentration also showed similar changes, which correlated with those of exfoliated colonic cells. A relationship between the beta-carotene content of the diet and that of the colonic epithelial cells suggests that analysis of the beta-carotene content in exfoliated human colonic epithelial cells is a useful non-invasive method to assess the bioavailability of provitamin A beta-carotene.

Analysis of codon usage in beta-tubulin sequences of helminths.

PubMed

von Samson-Himmelstjerna, G; Harder, A; Failing, K; Pape, M; Schnieder, T

2003-07-01

Codon usage bias has been shown to be correlated with gene expression levels in many organisms, including the nematode Caenorhabditis elegans. Here, the codon usage (cu) characteristics for a set of currently available beta-tubulin coding sequences of helminths were assessed by calculating several indices, including the effective codon number (Nc), the intrinsic codon deviation index (ICDI), the P2 value and the mutational response index (MRI). The P2 value gives a measure of translational pressure, which has been shown to be correlated to high gene expression levels in some organisms, but it has not yet been analysed in that respect in helminths. For all but two of the C. elegans beta-tubulin coding sequences investigated, the P2 value was the only index that indicated the presence of codon usage bias. Therefore, we propose that in general the helminth beta-tubulin sequences investigated here are not expressed at high levels. Furthermore, we calculated the correlation coefficients for the cu patterns of the helminth beta-tubulin sequences compared with those of highly expressed genes in organisms such as Escherichia coli and C. elegans. It was found that beta-tubulin cu patterns for all sequences of members of the Strongylida were significantly correlated to those for highly expressed C. elegans genes. This approach provides a new measure for comparing the adaptation of cu of a particular coding sequence with that of highly expressed genes in possible expression systems.Finally, using the cu patterns of the sequences studied, a phylogenetic tree was constructed. The topology of this tree was very much in concordance with that of a phylogeny based on small subunit ribosomal DNA sequence alignments.

Thalassemia major and consanguinity in Shiraz city, Iran.

PubMed

Asadi-Pooya, Ali Akbar; Doroudchi, Mehrnoosh

2004-09-05

Beta-thalassemia is among the most common genetic disorders in the world and in Iran, with widespread occurrence. A cross-sectional study on 648 beta-thalassemia patients in Shiraz, Iran was carried out to determine the demography of beta-thalassemia major in Shiraz city, Fars province, Iran and also the rate of consanguinity and the significance of pre-marriage counseling in decreasing familial marriages and consequently preventing this autosomal recessive genetic disease. All interviewed patients had thalassemia major and their age, sex, and the consanguinity between parents were recorded. 40.6% of beta-thalassemia patients were outcomes of first-cousin marriages. Comparison of the percentages of familial marriages (consanguinity) between parents of beta-thalassemia patients and a sample of normal population, revealed a statistically significant difference (p< 0.00001). A nonstatistically significant difference was observed between male (53.5%) and female (46.5%) thalassemia patients. Comparison of data with the situation in 22 years ago revealed a 16.4% decrease in familial marriages among thalassemic families, however, more education and awareness of young women and men about the increased risk of beta-thalassemia after familial marriage through pre-marriage counseling is still necessary.

Influence of beta-carotene on fertility in rabbits when using embryo transfer programs.

PubMed

Besenfelder, U; Solti, L; Seregi, J; Brem, G

1993-05-01

The effect of beta-carotene on reproduction traits in rabbits was studied in 509 (superovulated and normally ovulated) donors and 239 recipients by using embryo/gene transfer performed at 2 different locations. All of the bucks and the half of the females were fed a diet supplemented with 40 mg synthetic beta-carotene (Rovimix((R)))/kg feed. Embryos at the pronucleus stage were collected 19 to 21 hours after induction of ovulation with human chorionic gonadotropin (hCG); they were then microinjected into the male pronucleus and transferred to synchronized recipients. Data were obtained from the time when the donors and recipients were caged, until the pups resulting from the embryo transfers were weaned. Supplemented beta-carotene did not affect most of the 30 traits that were analyzed. However superovulated donors in Project 2 that received the beta-carotene enriched diet had a 14% lighter ovary weight (P<0.05) and less than half of the oocytes were unfertilized (P<0.05). In Project 1 (beta-carotene group) there was a greater number of pups born (36%, P<0.05) and more of these pups were born alive (53%, P<0.05).

Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kyle, J.W.; Vogler, C.; Hoffmann, J.W.

1990-05-01

The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{supmore » mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.« less

beta-catenin mediates insulin-like growth factor-I actions to promote cyclin D1 mRNA expression, cell proliferation and survival in oligodendroglial cultures.

PubMed

Ye, Ping; Hu, Qichen; Liu, Hedi; Yan, Yun; D'ercole, A Joseph

2010-07-01

By promoting cell proliferation, survival and maturation insulin-like growth factor (IGF)-I is essential to the normal growth and development of the central nervous system. It is clear that IGF-I actions are primarily mediated by the type I IGF receptor (IGF1R), and that phosphoinositide 3 (PI3)-Akt kinases and MAP kinases signal many of IGF-I-IGF1R actions in neural cells, including oligodendrocyte lineage cells. The precise downstream targets of these signaling pathways, however, remain to be defined. We studied oligodendroglial cells to determine whether beta-catenin, a molecule that is a downstream target of glycogen synthase kinase-3beta (GSK3beta) and plays a key role in the Wnt canonical signaling pathway, mediates IGF-I actions. We found that IGF-I increases beta-catenin protein abundance within an hour after IGF-I-induced phosphorylation of Akt and GSK3beta. Inhibiting the PI3-Akt pathway suppressed IGF-I-induced increases in beta-catenin and cyclin D1 mRNA, while suppression of GSK3beta activity simulated IGF-I actions. Knocking-down beta-catenin mRNA by RNA interference suppressed IGF-I-stimulated increases in the abundance of cyclin D1 mRNA, cell proliferation, and cell survival. Our data suggest that beta-catenin is an important downstream molecule in the PI3-Akt-GSK3beta pathway, and as such it mediates IGF-I upregulation of cyclin D1 mRNA and promotion of cell proliferation and survival in oligodendroglial cells. Copyright 2010 Wiley-Liss, Inc.

Mutational analysis of the folding transition state of the C-terminal domain of ribosomal protein L9: a protein with an unusual beta-sheet topology.

PubMed

Li, Ying; Gupta, Ruchi; Cho, Jae-Hyun; Raleigh, Daniel P

2007-01-30

The C-terminal domain of ribosomal protein L9 (CTL9) is a 92-residue alpha-beta protein which contains an unusual three-stranded mixed parallel and antiparallel beta-sheet. The protein folds in a two-state fashion, and the folding rate is slow. It is thought that the slow folding may be caused by the necessity of forming this unusual beta-sheet architecture in the transition state for folding. This hypothesis makes CTL9 an interesting target for folding studies. The transition state for the folding of CTL9 was characterized by phi-value analysis. The folding of a set of hydrophobic core mutants was analyzed together with a set of truncation mutants. The results revealed a few positions with high phi-values (> or = 0.5), notably, V131, L133, H134, V137, and L141. All of these residues were found in the beta-hairpin region, indicating that the formation of this structure is likely to be the rate-limiting step in the folding of CTL9. One face of the beta-hairpin docks against the N-terminal helix. Analysis of truncation mutants of this helix confirmed its importance in folding. Mutations at other sites in the protein gave small phi-values, despite the fact that some of them had major effects on stability. The analysis indicates that formation of the antiparallel hairpin is critical and its interactions with the first helix are also important. Thus, the slow folding is not a consequence of the need to fully form the unusual three-stranded beta-sheet in the transition state. Analysis of the urea dependence of the folding rates indicates that mutations modulate the unfolded state. The folding of CTL9 is broadly consistent with the nucleation-condensation model of protein folding.

Anti-Toxoplasma gondii antibodies in patients with beta-hemoglobinopathies: the first report in the Americas.

PubMed

Ferreira, Marina Neves; Bonini-Domingos, Claudia Regina; Fonseca Estevão, Isabeth; de Castro Lobo, Clarice Lopes; Souza Carrocini, Gisele Cristina; Silveira-Carvalho, Aparecida Perpétuo; Ricci, Octávio; de Mattos, Luiz Carlos; Brandão de Mattos, Cinara Cássia

2017-06-14

In Brazil, there have been no previous studies of Toxoplasma gondii infection in sickle cell anemia patients and carriers of severe forms of beta-thalassemia. This study evaluated T. gondii infection in patients with beta-hemoglobinopathies. A total of 158 samples, 77 (48.7%) men and 81 (51.3%) women, were evaluated. Three groups were formed: G1 (85 patients with sickle cell disease); G2 (11 patients with homozygous beta-thalassemia; G3 (62 patients with heterozygous beta-thalassemia). ELISA was employed to identify anti-T. gondii IgM and IgG antibodies, and molecular analysis was performed to determine beta-hemoglobin mutations. Fisher's exact test was used to compare frequencies of anti-T. gondii IgM and IgG antibodies in respect to gender and age. Anti-T. gondii IgG antibodies were found in 43.5% of individuals in G1, 18.1% in G2 and 50% in G3. All samples from G1 and G2 were seronegative for anti-T. gondii IgM antibodies, but 3.2% from G3 were seropositive. Considering anti-T. gondii IgG antibodies, no statistical significant differences were found between these groups nor in seroprevalence between genders within each group. Despite this, comparisons of the mean ages between G1, G2 and G3 were statistically significant (G2 vs. G1: p value = 0.0001; G3 vs. G1: p-value <0.0001; G3 vs. G2: p-value = 0.0001). A comparison by age of patients with sickle cell anemia showed a trend of lower risk of infection among younger individuals. Therefore, this study demonstrates that T. gondii infection occurs in patients with beta-thalassemia and sickle cell anemia in Brazil as seen by the presence of anti-T. gondii IgM and IgG antibodies.

The radial-azimuthal stability of accretion disks - Gas pressure contributions

NASA Technical Reports Server (NTRS)

Mckee, M. R.

1991-01-01

A radial-azimuthal stability analysis of a thin, alpha disk accretion flow is presented. The proportion of radiation pressure, Pr, of the unperturbed flow is allowed to vary according to the parameter beta = Pr/P, where P is the total pressure. As is the case for a purely radial analysis, the disk is stable for beta equal to or less than 0.6. However, the coupling of radial and azimuthal perturbations eliminates the viscous instability for such nonradial modes for all values of beta. The group velocity of the retrograde thermal mode is calculated as a function of beta.

Radioactive status of seawater and its assessment in the northeast South China Sea and the Luzon Strait and its adjacent areas from 2011 to 2014.

PubMed

Zhou, Peng; Li, Dongmei; Zhao, Li; Li, Haitao; Zhao, Feng; Zheng, Yuanlai; Fang, Hongda; Lou, Quansheng; Cai, Weixu

2018-06-01

To understand the impact of the Fukushima nuclear accident (FNA), 137 Cs, 134 Cs, 90 Sr, and gross beta were analyzed in the northeast South China Sea (NSCS), the Luzon Strait (LS) and its adjacent areas. 137 Cs, 90 Sr, and gross beta values in the NSCS were similar to those prior to the FNA. 90 Sr and 137 Cs in the LS and its adjacent areas were consistent with those in the NSCS. The high 137 Cs-peak values occurred at depth of 150 m whereas the high 90 Sr-peak values occurred at depth of 0.5 m. The 137 Cs and gross beta mean values in Cruise I were higher than those in Cruise II whereas the 90 Sr mean value was just the reverse. 134 Cs in all seawater were below the minimum detectable activity. The past and present data since the 1970s suggested 137 Cs and 90 Sr in the study areas still originated from global fallout and the FNA influence were negligible. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extraction and characterization of beta-D-glucan from oat for industrial utilization.

PubMed

Ahmad, Asif; Anjum, Faqir Muhammad; Zahoor, Tahir; Nawaz, Haq; Ahmed, Zaheer

2010-04-01

Oat beta-D-glucan is a valuable functional ingredient having numerous industrial, nutritional and health benefits. Its extraction needs careful attention as extraction process may affect the physiochemical and functional properties of extracted beta-D-glucan. The present study aimed at analyzing the effect of extraction of beta-D-glucan gum pellets from oat cultivar followed by detailed chemical and functional analysis. Enzymatic extraction process resulted in highest yield and recovery. Chemical analysis revealed protein as a dominating impurity. The water binding capacity of the beta-D-glucan ranged between 3.14 and 4.52 g g(-1) of sample. beta-D-Glucan exhibited ideal foaming stability when appropriate extraction technique was used. The viscosity of beta-D-glucan gum ranged between 35.6 and 56.16 cp. The color analysis showed L* value of beta-D-glucan gum pellet ranged between 72.18 and 83.54. Phosphorus, potassium and calcium appeared as major minerals in beta-D-glucan gum whereas iron, manganese and copper appeared as minor minerals. FTIR spectroscopy also confirms the presence of beta-D-glucan, protein and other components in extracted beta-D-glucan gum pellets. Overall, extracted beta-D-glucan showed a good potential for industrial usage. Copyright 2010 Elsevier B.V. All rights reserved.

The impact of fetal gender on first trimester nuchal translucency and maternal serum free beta-hCG and PAPP-A MoM in normal and trisomy 21 pregnancies.

PubMed

Cowans, Nicholas J; Stamatopoulou, Anastasia; Maiz, Nerea; Spencer, Kevin; Nicolaides, Kypros H

2009-06-01

To investigate if fetal sex has an impact on 1st trimester combined screening for aenuploidy. We studied the first trimester PAPP-A, free beta-human chorionic gonadatropin (beta-hCG) and nuchal translucency levels in 56,024 normal, singleton pregnancies with known fetal sex at birth. We also examined the distributions in 722 pregnancies with trisomy 21 of known fetal sex. We have found a 14.74% increase in first trimester maternal serum (MS) median free beta-hCG MoM, 6.25% increase of PAPP-A and a 9.41% decrease in delta NT, when the fetus was female. Analysis of data has shown that women carrying a female fetus were 1.084 times more likely to be in the 'at risk' group than those carrying a male fetus. In examining data from 722 pregnancies in which the fetus was affected by trisomy 21, we observed a similar 20.8% increase in free beta-hCG MoM, 5.7% increase in PAPP-A and a 12% decrease in delta NT when the fetus was female. Amongst the trisomy 21 cases, 88.8% of male trisomy 21 cases were detected compared with 91.2% in female cases, this difference was not statistically significant. Correcting for fetal sex redressed the balance in screen-positive rate between the sexes and had a minimal impact on detection rate. Correcting for fetal sex may be a worthwhile consideration. A cost-benefit analysis would be required to determine if it is feasible to introduce fetal gender assignment into the routine first trimester scan for the purpose of marker correction and whether this would have any significant impact. (c) 2009 John Wiley & Sons, Ltd.

Depression and anxiety as predictors of heart rate variability after myocardial infarction.

PubMed

Martens, E J; Nyklícek, I; Szabó, B M; Kupper, N

2008-03-01

Reduced heart rate variability (HRV) is a prognostic factor for cardiac mortality. Both depression and anxiety have been associated with increased risk for mortality in cardiac patients. Low HRV may act as an intermediary in this association. The present study examined to what extent depression and anxiety differently predict 24-h HRV indices recorded post-myocardial infarction (MI). Ninety-three patients were recruited during hospitalization for MI and assessed on self-reported symptoms of depression and anxiety. Two months post-MI, patients were assessed on clinical diagnoses of lifetime depressive and anxiety disorder. Adequate 24-h ambulatory electrocardiography data were obtained from 82 patients on average 78 days post-MI. In unadjusted analyses, lifetime diagnoses of major depressive disorder was predictive of lower SDNN [standard deviation of all normal-to-normal (NN) intervals; beta=-0.26, p=0.022] and SDANN (standard deviation of all 5-min mean NN intervals; beta=0.25, p=0.023), and lifetime anxiety disorder of lower RMSSD (root mean square of successive differences; beta=-0.23, p=0.039). Depression and anxiety symptoms did not significantly predict HRV. After adjustment for age, sex, cardiac history and multi-vessel disease, lifetime depressive disorder was no longer predictive of HRV. Lifetime anxiety disorder predicted reduced high-frequency spectral power (beta=-0.22, p=0.039) and RMSSD (beta=-0.25, p=0.019), even after additional adjustment of anxiety symptoms. Clinical anxiety, but not depression, negatively influenced parasympathetic modulation of heart rate in post-MI patients. These findings elucidate the physiological mechanisms underlying anxiety as a risk factor for adverse outcomes, but also raise questions about the potential role of HRV as an intermediary between depression and post-MI prognosis.

Prediction of beta-turns at over 80% accuracy based on an ensemble of predicted secondary structures and multiple alignments.

PubMed

Zheng, Ce; Kurgan, Lukasz

2008-10-10

beta-turn is a secondary protein structure type that plays significant role in protein folding, stability, and molecular recognition. To date, several methods for prediction of beta-turns from protein sequences were developed, but they are characterized by relatively poor prediction quality. The novelty of the proposed sequence-based beta-turn predictor stems from the usage of a window based information extracted from four predicted three-state secondary structures, which together with a selected set of position specific scoring matrix (PSSM) values serve as an input to the support vector machine (SVM) predictor. We show that (1) all four predicted secondary structures are useful; (2) the most useful information extracted from the predicted secondary structure includes the structure of the predicted residue, secondary structure content in a window around the predicted residue, and features that indicate whether the predicted residue is inside a secondary structure segment; (3) the PSSM values of Asn, Asp, Gly, Ile, Leu, Met, Pro, and Val were among the top ranked features, which corroborates with recent studies. The Asn, Asp, Gly, and Pro indicate potential beta-turns, while the remaining four amino acids are useful to predict non-beta-turns. Empirical evaluation using three nonredundant datasets shows favorable Q total, Q predicted and MCC values when compared with over a dozen of modern competing methods. Our method is the first to break the 80% Q total barrier and achieves Q total = 80.9%, MCC = 0.47, and Q predicted higher by over 6% when compared with the second best method. We use feature selection to reduce the dimensionality of the feature vector used as the input for the proposed prediction method. The applied feature set is smaller by 86, 62 and 37% when compared with the second and two third-best (with respect to MCC) competing methods, respectively. Experiments show that the proposed method constitutes an improvement over the competing prediction methods. The proposed prediction model can better discriminate between beta-turns and non-beta-turns due to obtaining lower numbers of false positive predictions. The prediction model and datasets are freely available at http://biomine.ece.ualberta.ca/BTNpred/BTNpred.html.

Role of the Frank-Starling mechanism in maintaining cardiac output during increasing levels of treadmill exercise in beta-blocked normal men.

PubMed

Bevilacqua, M; Savonitto, S; Bosisio, E; Chebat, E; Bertora, P L; Sardina, M; Norbiato, G

1989-04-01

To determine the effects of beta blockade on hemodynamics during increasing levels of treadmill exercise, 10 healthy volunteers were studied after 1 week of placebo, and then after 1 week of treatment with oral propranolol, 80 mg twice daily, or dilevalol, 400 mg once daily. The study was randomized and double-blind, with a crossover sequence. Hemodynamics were measured by CO2 rebreathing at rest and at 25, 50, 75 and 100% of VO2 max. After placebo, cardiac output increased from 5.8 +/- 2.1 (rest), to 19.4 +/- 6.4 liters/min (100% VO2 max), mainly due to an increase in heart rate from 84 +/- 6 to 169 +/- 15 beats/min. Stroke volume increased from 70 +/- 27 (rest), to 137 +/- 65 ml (25% VO2 max), and then leveled off to 116 +/- 41 at 100% VO2 max. After both beta blockers, exercise cardiac output was maintained at 100% VO2 max: 20.1 +/- 9.3 liters/min with propranolol and 19.1 +/- 8.6 with dilevalol. However, a significant reduction versus placebo values was observed for cardiac output at 25% VO2 max, from 13.7 +/- 5.9 during placebo, to 9.4 +/- 2.5 during propranolol, and to 9.6 +/- 2.3 during dilevalol (both p less than 0.01 vs placebo). Maintenance of cardiac output with both beta blockers at higher levels of exercise came from an increased stroke volume (p less than 0.05 vs placebo), while heart rate (in beats/min) was greatly reduced (propranolol 61.6 +/- 9.4 rest, 90.1 +/- 10.7 at 100% VO2 max; dilevalol 70.8 +/- 6.4 rest, 99.2 +/- 11.8 at 100% VO2 max, p less than 0.01 vs placebo for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.

PubMed

Bartlett, Thomas E; Zaikin, Alexey; Olhede, Sofia C; West, James; Teschendorff, Andrew E; Widschwendter, Martin

2013-01-01

Epigenetic processes--including DNA methylation--are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that methylation levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene methylation architecture is corrupted in cancer and whether the variability of levels of methylation of individual CpGs within a defined gene is able to discriminate cancerous from normal tissue, and is associated with heterogeneous tumour phenotype, as defined by gene expression. We analysed 270985 CpGs annotated to 18272 genes, in 3284 cancerous and 681 normal samples, corresponding to 14 different cancer types. In doing so, we found novel differences in intra-gene methylation pattern across phenotypes, particularly in those genes which are crucial for stem cell biology; our measures of intra-gene methylation architecture are a better determinant of phenotype than measures based on mean methylation level alone (K-S test [Formula: see text] in all 14 diseases tested). These per-gene methylation measures also represent a considerable reduction in complexity, compared to conventional per-CpG beta-values. Our findings strongly support the view that intra-gene methylation architecture has great clinical potential for the development of DNA-based cancer biomarkers.

Brain Cell Swelling During Hypocapnia Increases with Hyperglycemia or Ketosis

PubMed Central

Glaser, Nicole; Bundros, Angeliki; Anderson, Steve; Tancredi, Daniel; Lo, Weei; Orgain, Myra; O'Donnell, Martha

2014-01-01

Severe hypocapnia increases the risk of DKA-related cerebral injury in children, but the reason for this association is unclear. To determine whether the effects of hypocapnia on the brain are altered during hyperglycemia or ketosis, we induced hypocapnia (pCO2 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451± 78 mg/dL) and 15 ketotic rats (beta-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO2 (40±3 mmHg). In a subset (n=35), after 2 hrs of hypocapnia, pCO2 levels were normalized (40±3 mmHg) and ADC and CBF measurements repeated. Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO2 after hypocapnia resulted in striatal hyperemia. These effects were not substantially altered by hyperglycemia or ketosis, however, declines in ADC during hypocapnia were greater during both hyperglycemia and ketosis. We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia. PMID:24443981

Trajectories of BMI change impact glucose and insulin metabolism.

PubMed

Walsh, E I; Shaw, J; Cherbuin, N

2018-03-01

The aim of this study was to examine, in a community setting, whether trajectory of weight change over twelve years is associated with glucose and insulin metabolism at twelve years. Participants were 532 community-living middle-aged and elderly adults from the Personality and Total Health (PATH) Through Life study. They spanned the full weight range (underweight/normal/overweight/obese). Latent class analysis and multivariate generalised linear models were used to investigate the association of Body Mass Index (BMI, kg/m 2 ) trajectory over twelve years with plasma insulin (μlU/ml), plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at follow-up. All models were adjusted for age, gender, hypertension, pre-clinical diabetes status (normal fasting glucose or impaired fasting glucose) and physical activity. Four weight trajectories were extracted; constant normal (mean baseline BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI, individuals in the constant high and increase trajectories had significantly higher plasma insulin, greater insulin resistance, and higher beta cell function than those in the constant normal trajectory. Individuals in the decrease trajectory did not differ from the constant normal trajectory. Current BMI significantly interacted with preceding BMI trajectory in its association with plasma insulin, insulin resistance, and beta cell function. The trajectory of preceding weight has an independent effect on blood glucose metabolism beyond body weight measured at any given point in time. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.