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Sample records for metilbutirato hmb aumenta

  1. Photochemistry of a dual-bacteriorhodopsin system in Haloarcula marismortui: HmbRI and HmbRII.

    PubMed

    Tsai, Fu-Kuo; Fu, Hsu-Yuan; Yang, Chii-Shen; Chu, Li-Kang

    2014-07-03

    Recently, a dual-bacteriorhodopsin system, containing HmbRI and HmbRII, has been found in Haloarcula marismortui (Mol. Microbiol. 2013, 88, 551-561), and the light-driven proton pump activities were intrinsically different in a wide pH range. Compared with bacteriorhodopsin in H. salinarum (HsbR), the identical steady-state absorption contours of HsbR and HmbRs in the visible range indicated similarities in the retinal pocket. In addition, other reactive residues, including the proton relay channel, proton release group, and proton collecting funnel at the cytoplasm, were mostly conserved. We employed transient absorption spectroscopy and global analysis to characterize the photocycle intermediates and kinetics of HmbRI and HmbRII in the pH range of 4-8. The features of the time-resolved difference spectra of HmbRI indicated that the photocycle of HmbRI mainly followed the conventional pathway, including intermediates M, N, and O. A minute bypassed pathway from intermediate M needed to be included to better match the experimental data. The corresponding intermediate M' is attributed to the all-trans deprotonated Schiff base retinal, indicating the occurrence of retinal reisomerization prior to the reprotonation of the deprotonated Schiff base following the decay of intermediate M. Regarding HmbRII, its photocycle only followed the intermediates M and N, without intermediate O. The plausible molecular mechanisms, including the effects of the lengths of the loops and the distribution of the charged residues in the bacterio-opsin interior, were proposed to explain the differences in the photocycles. The pH-dependent photocycles were also investigated, and the results supported our proposed mechanism. Unravelling the photocycles of the HmbRs in the Haloarcula marismortui provided evidence that not only expanding the functional pH ranges but also the turnover kinetics are the strategies of the dual-bR system in the evolution of microbes in extreme environments.

  2. International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)

    PubMed Central

    2013-01-01

    Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations. PMID:23374455

  3. Epidemiological evidence for the role of the hemoglobin receptor, hmbR, in meningococcal virulence.

    PubMed

    Harrison, Odile B; Evans, Nicholas J; Blair, Jessica M; Grimes, Holly S; Tinsley, Colin R; Nassif, Xavier; Kriz, Paula; Ure, Roisin; Gray, Steve J; Derrick, Jeremy P; Maiden, Martin C J; Feavers, Ian M

    2009-07-01

    The distribution of the hemoglobin receptor gene (hmbR) was investigated among disease and carriage Neisseria meningitidis isolates, revealing that the gene was detected at a significantly higher frequency among disease isolates than among carriage isolates. In isolates without hmbR, the locus was occupied by the cassettes exl2 or exl3 or by a "pseudo hmbR" gene, designated exl4. The hmbR locus exhibited characteristics of a pathogenicity island in published genomes of N. meningitidis, Neisseria gonorrhoeae, and Neisseria lactamica sequence type-640. These data are consistent with a role for the hmbR gene in meningococcal disease.

  4. Characterisation of equine satellite cell transcriptomic profile response to β-hydroxy-β-methylbutyrate (HMB).

    PubMed

    Szcześniak, Katarzyna A; Ciecierska, Anna; Ostaszewski, Piotr; Sadkowski, Tomasz

    2016-10-01

    β-Hydroxy-β-methylbutyrate (HMB) is a popular ergogenic aid used by human athletes and as a supplement to sport horses, because of its ability to aid muscle recovery, improve performance and body composition. Recent findings suggest that HMB may stimulate satellite cells and affect expressions of genes regulating skeletal muscle cell growth. Despite the scientific data showing benefits of HMB supplementation in horses, no previous study has explained the mechanism of action of HMB in this species. The aim of this study was to reveal the molecular background of HMB action on equine skeletal muscle by investigating the transcriptomic profile changes induced by HMB in equine satellite cells in vitro. Upon isolation from the semitendinosus muscle, equine satellite cells were cultured until the 2nd day of differentiation. Differentiating cells were incubated with HMB for 24 h. Total cellular RNA was isolated, amplified, labelled and hybridised to microarray slides. Microarray data validation was performed with real-time quantitative PCR. HMB induced differential expressions of 361 genes. Functional analysis revealed that the main biological processes influenced by HMB in equine satellite cells were related to muscle organ development, protein metabolism, energy homoeostasis and lipid metabolism. In conclusion, this study demonstrated for the first time that HMB has the potential to influence equine satellite cells by controlling global gene expression. Genes and biological processes targeted by HMB in equine satellite cells may support HMB utility in improving growth and regeneration of equine skeletal muscle; however, the overall role of HMB in horses remains equivocal and requires further proteomic, biochemical and pharmacokinetic studies.

  5. [Contribution of monoclonal antibody HMB45 in the histopathologic diagnosis of melanoma].

    PubMed

    Pluot, M; Joundi, A; Grosshans, E

    1990-01-01

    We have tested the diagnostic value in malignant melanoma of HMB45, a monoclonal antibody available for use on paraffin-embedded tissue. MATERIAL AND METHOD. Tissues tested. The following pathological tissues were tested: 10 intradermal and 11 compound naevi; 6 spitz naevi; 20 dysplastic naevi; 10 blue naevi; 2 Bednar's tumours; 6 Sutton naevi; 15 melanonychias; 21 cutaneous and 11 ocular malignant melanomas (MM), and 3 achromic metastases. Control tissues were: vitiligo (20), carcinoma (5), malignant schwannoma of the orbit (1), soft tissue sarcoma (5) and malignant lymphoma (5). Antibodies. The antibodies used were antiprotein S100, antivimentin, anticytokeratin (KL1), monoclonal antileucocyte (CD45) antibodies and HMB45, a monoclonal antibody of the IgG 1 type obtained from lymph node metastases from pigmented malignant melanomas. RESULTS. None of the control tissues were stained by the HMB Ab. Intradermal naevi did not react positively. Compound naevi: the juntional cells were stained by HMB45 in 2/10 cases. Dysplastic naevi: HMB45 showed heterogeneous reactivity of junctional cells in 15/20 cases, and this correlated with the degree of atypia. Blue naevi: HMB45 stained the superficial and deep cells in 3/10 cases. Bednar's tumour: no cell was stained by HMB45. Spitz naevi: HMB45 gave an intensely positive reaction of junctional cells in 4/5 cases and a weaker reaction of dermal cells. Sutton naevi: the naevus cells were not stained by HMB45 in 5/6 cases. In simple melanocytic hyperplasia of the nail bed, only a few atypical cells were stained. In superficially spreading melanoma (SSM) all neoplastic cells were stained by HMB45 in proportion to their degree of atypia. Residual naevus cells were negative. The anti S100 and the antivimentin antibodies stained all neoplastic and naevus cells. In nodular melanoma (NM), HMB45 stained all neoplastic cells in proportion to their degree of atypia. The antivimentin Ab stained the neoplastic cells, and so did the anti

  6. A very rare case of uterine PEComa HMB45 negative: primitive or relapse?

    PubMed Central

    Pecorino, Basilio; Scibilia, Giuseppe; Galia, Antonio; Scollo, Paolo

    2016-01-01

    Perivascular epithelioid cell tumors (PEComas) represent a rare group of tumours with uncertain malignancy potential exhibiting an immunophenotype characterized by actin and Human Melanoma Black 45 (HMB45) immunoreactivity. Our case concerns about a rare malignant uterine perivascular epithelioid cell tumour diagnosed in a patient underwent to subtotal hysterectomy with unclear diagnosis, 12 years before. Histological diagnosis after colposcopic exam with biopsy revealed a perivascular epithelioid cell tumor, with immunohistochemical profle negative for HMB45. Negativity for HMB45, already described in literature, could be due to important cellular modifcations of tumoral tissue. In our case, tumour was unresectable, progression of disease occurred during medical treatment and the patient died after 6 months. Lack of information about frst surgery doesn't allow to surely categorized the tumor as primitive or relapse. Further studies are necessary to understand some immunohistochemical anomaly like negativity for HMB45. PMID:26900338

  7. β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells

    PubMed Central

    Girón, María D.; Cabrera, Elena; Campos, Nefertiti; Manzano, Manuel; Rueda, Ricardo; López-Pedrosa, Jose M.

    2015-01-01

    β-Hydroxy-β-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth. PMID:26267903

  8. β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells.

    PubMed

    Salto, Rafael; Vílchez, Jose D; Girón, María D; Cabrera, Elena; Campos, Nefertiti; Manzano, Manuel; Rueda, Ricardo; López-Pedrosa, Jose M

    2015-01-01

    β-Hydroxy-β-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth.

  9. Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program.

    PubMed

    Jówko, E; Ostaszewski, P; Jank, M; Sacharuk, J; Zieniewicz, A; Wilczak, J; Nissen, S

    2001-01-01

    We investigated whether creatine (CR) and beta-hydroxy-beta-methylbutyrate (HMB) act by similar or different mechanisms to increase lean body mass (LBM) and strength in humans undergoing progressive resistance-exercise training. In this double-blind, 3-wk study, subjects (n = 40) were randomized to placebo (PL; n = 10), CR (20.0 g of CR/d for 7 d followed by 10.0 g of CR/d for 14 d; n = 11), HMB (3.0 g of HMB/d; n = 9), or CR-and-HMB (CR/HMB; n = 10) treatment groups. Over 3 wk, all subjects gained LBM, which was assessed by bioelectrical impedance analysis. The CR, HMB and CR/HMB groups gained 0.92, 0.39, and 1.54 kg of LBM, respectively, over the placebo group, with a significant effect with CR supplementation (main effect P = 0.05) and a trend with HMB supplementation (main effect P = 0.08). These effects were additive because there was no interaction between CR and HMB (CR x HMB main effect P = 0.73). Across all exercises, HMB, CR, and CR/HMB supplementation caused accumulative strength increases of 37.5, 39.1, and 51.9 kg, respectively, above the placebo group. The exercise-induced rise in serum creatine phosphokinase was markedly suppressed with HMB supplementation (main effect P = 0.01). However, CR supplementation antagonized the HMB effects on serum creatine phosphokinase (CR x HMB interactive effect P = 0.04). Urine urea nitrogen and plasma urea were not affected by CR supplementation, but both decreased with HMB supplementation (HMB effect P < 0.05), suggesting a nitrogen-sparing effect. In summary, CR and HMB can increase LBM and strength, and the effects are additive. Although not definitive, these results suggest that CR and HMB act by different mechanisms.

  10. beta-hydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors.

    PubMed

    Nissen, S; Sharp, R L; Panton, L; Vukovich, M; Trappe, S; Fuller, J C

    2000-08-01

    The leucine metabolite, beta-hydroxy-beta-methylbutyrate (HMB) enhances the effects of exercise on muscle size and strength. Although several reports in animals and humans indicate that HMB is safe, quantitative safety data in humans have not been reported definitively. The objective of this work was to summarize safety data collected in nine studies in which humans were fed 3 g HMB/d. The studies were from 3 to 8 wk in duration, included both males and females, young and old, exercising or nonexercising. Organ and tissue function was assessed by blood chemistry and hematology; subtle effects on emotional perception were measured with an emotional profile test (Circumplex), and tolerance of HMB was assessed with a battery of 32 health-related questions. HMB did not adversely affect any surrogate marker of tissue health and function. The Circumplex emotion profile indicated that HMB significantly decreased (improved) one indicator of negative mood (Unactivated Unpleasant Affect category, P < 0.05). No untoward effects of HMB were indicated. Compared with the placebo, HMB supplementation resulted in a net decrease in total cholesterol (5.8%, P < 0.03), a decrease in LDL cholesterol (7.3%, P < 0.01) and a decrease in systolic blood pressure (4.4 mm Hg, P < 0.05). These effects of HMB on surrogate markers of cardiovascular health could result in a decrease in the risk of heart attack and stroke. In conclusion, the objective data collected across nine experiments indicate that HMB can be taken safely as an ergogenic aid for exercise and that objective measures of health and perception of well-being are generally enhanced.

  11. β-hydroxy β-methylbutyrate (HMB) supplementation effects on body mass and performance in elite male rugby union players.

    PubMed

    McIntosh, Nicholas D; Love, Thomas D; Haszard, Jillian; Osborne, Hamish; Black, Katherine E

    2016-10-27

    Pre-season is characterized by high training volumes with short recovery periods β-hydroxy β-methylbutyrate (HMB) has been postulated to assist with recovery. HMB has been shown to improve strength and body composition amongst untrained groups the benefits of HMB amongst trained populations are unclear due to the methodologies employed. This randomized control trail determined the effects of 11 weeks HMB supplementation on body mass and performance measures in 27 elite rugby players. HMB group (n=13) mean±SD age 20.3±1.2 years, body mass 99.6±9.1 kg; placebo group (n=14), age 21.9±2.8 years body mass 99.4±13.9 kg for placebo. During the supplementation period body mass increased with HMB 0.57±2.60 kg but decreased with placebo 1.39±2.02 kg (p=0.029). There were no significant differences in any of the four strength variables (p>0.05). However, on the YoYo IR-1 the placebo group improved 4.0±2.8 levels but HMB decreased 2.0±3.0 levels (p=0.003). The results of this study suggest HMB could be beneficial for gaining or maintaining body mass during periods of increased training load. However, it appears that HMB may be detrimental to intermittent running ability in this group, although further research is required before firm conclusions can be made. Only 6 participants on HMB managed to complete both YoYo IR-1 tests due to injury, a larger sample size is required to fully investigate this potentially negative effect. Further, the mechanisms behind this decrement in performance cannot be fully explained and requires further biochemical and psychological investigation.

  12. HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise.

    PubMed

    Park, Bong-Sup; Henning, Paul C; Grant, Samuel C; Lee, Won Jun; Lee, Sang-Rok; Arjmandi, Bahram H; Kim, Jeong-Su

    2013-12-01

    To investigate the efficacy and underlying mechanisms of β-hydroxy-β-methylbutyrate (HMB) on body composition, muscle mass and physical performance under catabolic versus normal training conditions. Mice were divided into four groups (n=10/group): (1) ALT=ad libitum+trained (1 h/d for 3 d/wk); (2) ALTH=ALT+HMB (0.5 g/kg BW/d); (3) C=calorie restricted (-30%)+trained (6 h/d, 6 d/wk); and (4) CH=C+HMB. Repeated in vivo assessments included body composition, grip strength and sensorimotor coordination before and after the experimental protocol, while in vitro analyses included muscle wet weights, expression of selected genes and proteins regulating muscle mass, and myofiber cross-sectional area. ANOVAs were used with significance set at p<0.05. ALTH had greater lean mass than ALT and sensorimotor function increased in ALTH, but decreased in ALT under normal training conditions. Grip strength decreased only in C, but was maintained in CH. Gastrocnemius mass and myofiber CSA were greater in CH than C following catabolic conditions. Gastrocnemius atrogin-1 mRNA expression was elevated in C but not in CH compared to all other groups whereas atrogin-1 protein levels showed no significant changes. HMB improves body composition and sensorimotor function during normal training and attenuates muscle mass and strength loss during catabolic conditions. © 2013.

  13. Prenatally administered HMB modifies the enamel surface roughness in spiny mice offspring: An atomic force microscopy study.

    PubMed

    Świetlicka, Izabela; Muszyński, Siemowit; Tomaszewska, Ewa; Dobrowolski, Piotr; Kwaśniewska, Anita; Świetlicki, Michał; Skic, Anna; Gołacki, Krzysztof

    2016-10-01

    The aim of this research was to check the effect of the prenatally administered β-hydroxy β-methylbutyrate (HMB) on the development of enamel surface of the spiny mice offspring. The spiny mice dams were randomly assigned into three groups: control group (not supplemented with HMB) and two experimental groups in which powdered HMB was given at the daily dosage of 0.2g/kg of body weight (group I) and 0.02g/kg of body weight (group II) during the last period of gestation. Newborn pups were euthanized by CO2 inhalation. The morphology of incisor teeth was analysed using atomic force microscopy (AFM) in semi-contact mode in the height, magnitude and phase domains. Height images became a basis for determination of surface roughness parameters. Conducted study indicated that maternal HMB administration markedly influences enamel development. Enamel of offspring's teeth in both experimental groups was characterized by significantly smaller values of indices describing surface roughness and profile. HMB supplementation influenced the calculated parameters regardless of the diet type and offspring sex, however higher dose of HMB caused stronger changes in enamel surface's physical properties and could be observed in higher intensity in the male group. HMB administration caused reduction in the irregularities of enamel surface, thereby possibly reducing the probability of bacteria adhesion and caries development. These observations may serve to improve nutrition and supplementation of animals and could be a lead for further research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. USEFULNESS OF Β-HYDROXY-Β-METHYLBUTYRATE (HMB) SUPPLEMENTATION IN DIFFERENT SPORTS: AN UPDATE AND PRACTICAL IMPLICATIONS.

    PubMed

    Albert, Francisco J; Morente-Sánchez, Jaime; Ortega, Francisco B; Castillo, Manuel J; Gutiérrez, Ángel

    2015-07-01

    although -hydroxy--methylbutyrate (HMB) is generally marketed as a supplement for increasing muscle mass and strength, it is still not fully understood how and in which particular sports and conditions HMB can be more effective. the primary purpose of this review is to update and summarize the current knowledge about the usefulness of HMB and to organize this information by different sports with specific reference to sports with high wear and tear phenomena as soccer, rugby or football. a search was performed in PubMed database. This review presents the results about HMB use in sport. the articles identified in this review support the notion that HMB could help to attenuate tissue catabolism and initiate muscle anabolism particularly in untrained individuals exposed to strenuous exercise or when trained individual are exposed to periods of high physical stress. HMB could therefore be applied in some specific periods of athlete's season where there are high-intensity training periods, high density of competitions and little recovery time between them, starting recovery phases from an injury period and/or any other different situation where performance or recovery could be affected by a great catabolic environment. this update contributes to clarify and define possible mechanisms and/or effectiveness of HMB supplementation related to endurance sports (i.e. cycling and athletics), strength-power sports (i.e. resistance training, football, rugby, soccer, judo, waterpolo and rowing) and recreational activities. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  15. β-Hydroxy-β-methylbutyrate (HMB) normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.

    PubMed

    Girón, María D; Vílchez, Jose D; Shreeram, Sathyavageeswaran; Salto, Rafael; Manzano, Manuel; Cabrera, Elena; Campos, Nefertiti; Edens, Neile K; Rueda, Ricardo; López-Pedrosa, Jose M

    2015-01-01

    Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

  16. Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways.

    PubMed

    Kornasio, Reut; Riederer, Ingo; Butler-Browne, Gillian; Mouly, Vincent; Uni, Zehava; Halevy, Orna

    2009-05-01

    Beta-hydroxy-beta-methylbutyrate (HMB), a leucine catabolite, has been shown to prevent exercise-induced protein degradation and muscle damage. We hypothesized that HMB would directly regulate muscle-cell proliferation and differentiation and would attenuate apoptosis, the latter presumably underlying satellite-cell depletion during muscle degradation or atrophy. Adding various concentrations of HMB to serum-starved myoblasts induced cell proliferation and MyoD expression as well as the phosphorylation of MAPK/ERK. HMB induced differentiation-specific markers, increased IGF-I mRNA levels and accelerated cell fusion. Its inhibition of serum-starvation- or staurosporine-induced apoptosis was reflected by less apoptotic cells, reduced BAX expression and increased levels of Bcl-2 and Bcl-X. Annexin V staining and flow cytometry analysis showed reduced staurosporine-induced apoptosis in human myoblasts in response to HMB. HMB enhanced the association of the p85 subunit of PI3K with tyrosine-phosphorylated proteins. HMB elevated Akt phosphorylation on Thr308 and Ser473 and this was inhibited by Wortmannin, suggesting that HMB acts via Class I PI3K. Blocking of the PI3K/Akt pathway with specific inhibitors revealed its requirement in mediating the promotive effects of HMB on muscle cell differentiation and fusion. These direct effects of HMB on myoblast differentiation and survival resembling those of IGF-I, at least in culture, suggest its positive influence in preventing muscle wasting.

  17. Pancreatic PEComa: a case report with ultrastructural localization of HMB-45 within melanosomes.

    PubMed

    Finzi, Giovanna; Micello, Donata; Wizemann, Giorgio; Sessa, Fausto; Capella, Carlo

    2012-04-01

    PEComas (perivascular epithelioid cell tumors) represent a group of mesenchymal neoplasms showing characteristic morphologic, immunohistochemical, ultrastructural, and genetic features. These neoplasms are usually considered benign, being often well circumscribed by a thin capsule and showing scarce atypia. However, in some cases, they show local invasion and multiple metastases and cause the patient's death. PEComas have been found in many locations, but only 7 cases have been described in the pancreas to date. Here, the authors report an additional case of this rare neoplasm and demonstrate the HMB-45 immunoreactivity of melanosomes or premelanosomes at the ultrastructural level.

  18. Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats.

    PubMed

    Kougias, Daniel G; Hankosky, Emily R; Gulley, Joshua M; Juraska, Janice M

    2017-03-01

    Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze. Female rats were ovariectomized at 11months of age to model human menopause. At 12months of age, male and female rats received relatively short- or long-term (1- or 7-month) dietary HMB (450mg/kg/dose) supplementation twice a day prior to testing. Spatial reference learning and memory was assessed across four days in the water maze with four trials daily and a probe trial on the last day. Consistent with previous work, there were age-related deficits in water maze performance in both sexes. However, these deficits were ameliorated in HMB-treated males during training and in both sexes during probe trial performance. Thus, HMB supplementation prevented the age-related decrement in water maze performance, especially in male rats.

  19. The ergogenic supplement β-hydroxy-β-methylbutyrate (HMB) attenuates insulin resistance through suppressing GLUT-2 in rat liver.

    PubMed

    Sharawy, Maha H; El-Awady, Mohammed S; Megahed, Nirmeen; Gameil, Nariman M

    2016-05-01

    This study investigates the effect of the ergogenic supplement β-hydroxy-β-methylbutyrate (HMB) on insulin resistance induced by high-fructose diet (HFD) in rats. Male Sprague Dawley rats were fed 60% HFD for 12 weeks and HMB (320 mg·kg(-1)·day(-1), orally) for 4 weeks. HFD significantly increased fasting insulin, fasting glucose, glycosylated hemoglobin (HBA1C), liver glycogen content, and homeostasis model assessment of insulin resistance (HOMA-IR) index, while it decreased glucose and insulin tolerance. Furthermore, HFD significantly increased serum triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL-C) levels, while it significantly decreased high density lipoprotein cholesterol (HDL-C). Moreover, HFD significantly increased mRNA expression of glucose transporter type-2 (GLUT-2), the mammalian target of rapamycin (mTOR), and sterol regulatory element-binding protein-1c (SREBP-1c) but decreased peroxisome proliferator-activated receptor-alpha (PPAR-α) in liver. Aortic relaxation to acetylcholine (ACh) was impaired and histopathology showed severe hepatic steatosis. HMB significantly increased insulin tolerance and decreased fasting insulin, HOMA-IR, HBA1C, hepatic glycogen content, serum TG, LDL-C, and VLDL-C. Additionally, HMB enhanced ACh-induced relaxation, ameliorated hepatic steatosis, and decreased mRNA expression of GLUT-2. In conclusion, HMB may attenuate insulin resistance and hepatic steatosis through inhibiting GLUT-2 in liver.

  20. Protective effect of quercetin and luteolin in human melanoma HMB-2 cells.

    PubMed

    Horváthová, Katarína; Chalupa, Ivan; Sebová, Lívia; Tóthová, Darina; Vachálková, Anna

    2005-01-03

    Multifunctional effects of flavonoids are reported to be markedly connected with their structure and the functional groups in the molecule. The important role in the activity play C2-C3 double bond, hydroxyl group at C3 and the number of hydroxyl groups at phenyl ring (B). In this paper, the DNA protective free radical scavenging potential of quercetin (QU) and luteolin (LU) against H2O2 and their clastogenic effect alone and in combination with melphalan (MH) were investigated in human melanoma HMB-2 cells. Elevated frequency of chromosomal aberrations induced by MH, that at high doses have shown a variety of toxic side effects, was statistically decreased by studied flavonoids regarding to control (QU at the concentration of 50 microM and LU already at the concentration of 20 microM). The results concerning DNA protective potential against free radicals in HMB-2 cells demonstrated that QU and LU have significant effect in dose dependent manner. The percentage of QU protective effect is 40% at the concentration 20 microM, resp. 80% at the concentration 100 microM. Comparable values were obtained with LU. Results are correlated to their structural arrangement and organization of the hydroxyl groups.

  1. The relationship of endogenous plasma concentrations of β-Hydroxy β-Methyl Butyrate (HMB) to age and total appendicular lean mass in humans.

    PubMed

    Kuriyan, Rebecca; Lokesh, Deepa P; Selvam, Sumithra; Jayakumar, J; Philip, Mamatha G; Shreeram, Sathyavageeswaran; Kurpad, Anura V

    2016-08-01

    The maintenance of muscle mass and muscle strength is important for reducing the risk of chronic diseases. The age- related loss of muscle mass and strength is associated with adverse outcomes of physical disability, frailty and death. β-Hydroxy β-Methyl Butyrate (HMB), a metabolite of leucine, has beneficial effects on muscle mass and strength under various catabolic conditions. The objectives of the present study were to determine if age- related differences existed in endogenous plasma HMB levels, and to assess if HMB levels correlated to total appendicular lean mass and forearm grip strength. Anthropometry, dietary and physical activity assessment, and the estimation of fasting plasma HMB concentrations and handgrip strength were performed on the 305 subjects (children, young adults and older adults). Lean mass, which serves as a surrogate for muscle mass was measured using dual energy X-ray absorptiometry (DEXA). Mean plasma HMB concentrations were significantly lower with increasing age groups, with children having highest mean HMB concentration (p<0.01) followed by young adults and older adults. Female subjects (across all ages) had significantly lower plasma HMB concentrations. A significant positive correlation between HMB concentrations and appendicular lean mass normalized for body weight (%), appendicular lean mass (r=0.37; p<0.001) was observed in the young adults and older adults group. Handgrip strength was positively associated with plasma HMB concentrations in young adults (r=0.58; p<0.01) and the older adults group (r=0.28; p<0.01). The findings of the present study suggest that there is an age- related decline in endogenous HMB concentrations in humans and the HMB concentrations were positively correlated with appendicular lean mass and hand grip strength in young adults and older adults group.

  2. Immunohistochemical double stains against Ki67/MART1 and HMB45/MITF: promising diagnostic tools in melanocytic lesions.

    PubMed

    Nielsen, Patricia Switten; Riber-Hansen, Rikke; Steiniche, Torben

    2011-06-01

    Distinction between benign and malignant melanocytic lesions may be difficult by today's methods, even for highly skilled dermatopathologists, emphasizing the need for improved diagnostic tools. We have studied the discriminative abilities of immunohistochemical (IHC) double stains using the IHC markers Ki67 combined with MART1, and HMB45 combined with MITF. Paraffin-embedded tissue sections from 50 melanomas and 78 benign nevi were stained using a simple simultaneous IHC double staining technique. Both simple semiquantitative estimates of the immunopositivity in the deepest third of the lesions and full-scale quantitative measurements of the Ki67 and HMB45 indices were performed, and scores for melanomas and nevi were compared. The differences between melanomas and nevi were significant (P < 0.0001) using either analysis or stain. The misclassification rates for melanomas and nevi were generally lower for Ki67/MART1 stains than for HMB45/MITF stains. In the simple semiquantitative Ki67/MART1 analysis, the misclassification rates were 6% (2%-17%) for melanomas and 12% (6%-21%) for nevi. In full-scale quantitative analysis the corresponding rates were 4% (1%-14%) and 8% (4%-16%), and by combining Ki67 and HMB45 indices, the misclassification rates were 0% (0%-7%) for melanomas and 13% (7%-22%) for nevi. We conclude that both semiscale and fullscale quantitative analyses of Ki67/MART1 stains are valuable diagnostic tools to distinguish melanomas and nevi with a large degree of certainty. The HMB45/MITF stains may serve as adjuncts to predict malignancy and the diagnostic potential of combining the HMB45 and Ki67 indices are promising. The IHC double stains may potentially reduce misinterpretations of melanomas in histopathology.

  3. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review

    PubMed Central

    Wilson, Gabriel J; Wilson, Jacob M; Manninen, Anssi H

    2008-01-01

    The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been extensively used as an ergogenic aid; particularly among bodybuilders and strength/power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy. While numerous studies have supported the efficacy of HMB in exercise and clinical conditions, there have been a number of conflicting results. Therefore, the first purpose of this paper will be to provide an in depth and objective analysis of HMB research. Special care is taken to present critical details of each study in an attempt to both examine the effectiveness of HMB as well as explain possible reasons for conflicting results seen in the literature. Within this analysis, moderator variables such as age, training experience, various states of muscle catabolism, and optimal dosages of HMB are discussed. The validity of dependent measurements, clustering of data, and a conflict of interest bias will also be analyzed. A second purpose of this paper is to provide a comprehensive discussion on possible mechanisms, which HMB may operate through. Currently, the most readily discussed mechanism has been attributed to HMB as a precursor to the rate limiting enzyme to cholesterol synthesis HMG-coenzyme A reductase. However, an increase in research has been directed towards possible proteolytic pathways HMB may operate through. Evidence from cachectic cancer studies suggests that HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins. HMB may also directly stimulate protein synthesis, through an mTOR dependent mechanism. Finally, special care has been taken to provide future research implications. PMID:18173841

  4. Cellular and Physiological Effects of Dietary Supplementation with β-Hydroxy-β-Methylbutyrate (HMB) and β-Alanine in Late Middle-Aged Mice

    PubMed Central

    Vallejo, Julian; Spence, Madoka; Cheng, An-Lin; Brotto, Leticia; Edens, Neile K.; Garvey, Sean M.; Brotto, Marco

    2016-01-01

    There is growing evidence that severe decline of skeletal muscle mass and function with age may be mitigated by exercise and dietary supplementation with protein and amino acid ingredient technologies. The purposes of this study were to examine the effects of the leucine catabolite, beta-hydroxy-beta-methylbutyrate (HMB), in C2C12 myoblasts and myotubes, and to investigate the effects of dietary supplementation with HMB, the amino acid β-alanine and the combination thereof, on muscle contractility in a preclinical model of pre-sarcopenia. In C2C12 myotubes, HMB enhanced sarcoplasmic reticulum (SR) calcium release beyond vehicle control in the presence of all SR agonists tested (KCl, P<0.01; caffeine, P = 0.03; ionomycin, P = 0.03). HMB also improved C2C12 myoblast viability (25 μM HMB, P = 0.03) and increased proliferation (25 μM HMB, P = 0.04; 125 μM HMB, P<0.01). Furthermore, an ex vivo muscle contractility study was performed on EDL and soleus muscle from 19 month old, male C57BL/6nTac mice. For 8 weeks, mice were fed control AIN-93M diet, diet with HMB, diet with β-alanine, or diet with HMB and β-alanine. In β-alanine fed mice, EDL muscle showed a 7% increase in maximum absolute force compared to the control diet (202 ± 3vs. 188± 5 mN, P = 0.02). At submaximal frequency of stimulation (20 Hz), EDL from mice fed HMB plus β-alanine showed an 11% increase in absolute force (88.6 ± 2.2 vs. 79.8 ± 2.4 mN, P = 0.025) and a 13% increase in specific force (12.2 ± 0.4 vs. 10.8 ± 0.4 N/cm2, P = 0.021). Also in EDL muscle, β-alanine increased the rate of force development at all frequencies tested (P<0.025), while HMB reduced the time to reach peak contractile force (TTP), with a significant effect at 80 Hz (P = 0.0156). In soleus muscle, all experimental diets were associated with a decrease in TTP, compared to control diet. Our findings highlight beneficial effects of HMB and β-alanine supplementation on skeletal muscle function in aging mice. PMID

  5. β-Hydroxy-β-methylbutyrate (HMB) enhances the proliferation of satellite cells in fast muscles of aged rats during recovery from disuse atrophy.

    PubMed

    Alway, Stephen E; Pereira, Suzette L; Edens, Neile K; Hao, Yanlei; Bennett, Brian T

    2013-09-01

    Loss of myonuclei by apoptosis is thought to contribute to sarcopenia. We have previously shown, that the leucine metabolite, β-hydroxy-β-methylbutyrate (HMB) suppresses apoptotic signaling and the apoptotic index (the ratio of apoptotic positive to apoptotic negative myonuclei) during muscle disuse and during reloading periods after disuse in aged rats. However, it was not clear if the apoptotic signaling indexes were due only to preservation of myonuclei or if perhaps the total myogenic pool increased as a result of HMB-mediated satellite cell proliferation as this would have also reduced the apoptotic index. In this study, we tested the hypothesis that HMB would augment myogenic cells (satellite cells) proliferation during muscle recovery (growth) after a period of disuse in senescent animals. The hindlimb muscles of 34 month old Fisher 344 × Brown Norway rats were unloaded for 14 days by hindlimb suspension (HLS), and then reloaded for 14 days. The rats received either Ca-HMB (340 mg/kg body weight; n = 16), or the vehicle (n = 10) by gavage throughout the experimental period. HMB prevented the functional decline in maximal plantar flexion isometric force production during the reloading period, but not during HLS. HMB-treatment enhanced the proliferation of muscle stem cells as shown by a greater percentage of satellite cells that had proliferated (more BrdU positive, Pax-7 positive, and more Pax7/Ki67 positive nuclei) and as a result, more differentiated stem cells were present (more MyoD/myogenin positive myonuclei), relative to total myonuclei, in reloaded plantaris muscles as compared to reloaded muscles from vehicle-treated animals. Furthermore HMB increased the nuclear protein abundance of proliferation markers, inhibitor of differentiation-2 and cyclin A, as compared to vehicle treatment in reloaded muscles. Although HMB increased phosphorylated Akt during reloading, other mTOR related proteins were not altered by HMB treatment. These data show that

  6. The effect of HMB ingestion on the IGF-I and IGF binding protein response to high intensity military training.

    PubMed

    Redd, Michael J; Hoffman, Jay R; Gepner, Yftach; Stout, Jeffrey R; Hoffman, Mattan W; Ben-Dov, Daniel; Funk, Shany; Church, David D; Avital, Guy; Chen, Yacov; Frankel, Hagai; Ostfeld, Ishay

    2017-02-01

    Insulin-like growth factor-I (IGF-I) is a metabolic and anabolic biomarker that has been proposed to reflect physiological adaptations resulting from multistressor environments. The bioactivity of IGF-I is regulated by seven different insulin-like growth factor binding proteins (IGFBPs) which act not only as carriers of IGF-1, but also function as a modulator of IGF-I availability and activity. Supplementing with β-hydroxy-β-methylbutyrate (HMB) has been shown to enhance physiological outcomes associated with intense training, and has been reported to augment the IGF-1 response. The purpose of this study was to examine the effect of 23days of HMB supplementation on circulating levels of IGF-I and IGFBPs in combat soldiers during highly intense military training. Thirteen male soldiers from an elite infantry unit volunteered to participate in this double-blind, parallel design study. Soldiers were provided 3g·day(-1) of either HMB (n=6) or placebo (PL; n=7). During the study soldiers performed advanced military training with periods of restricted sleep and severe environmental stressors. Blood samples were obtained prior to (PRE) and approximately 18h following the final supplement consumption (POST). No significant differences were observed for circulating IGF-1 concentrations between HMB and PL (p=0.568). In addition, no differences were seen between the groups for IGFBP-1 (p=1.000), IGFBP-2 (p=0.855), IGFBP-3 (p=0.520), IGFBP-4 (p=0.103), IGFBP-5 (p=0.886), or IGFBP-6 (p=0.775). A significant difference was noted between HMB (169.9±23.0ng·ml(-1)) and PL (207.2±28.0ng·ml(-1)) for IGFBP-7 at POST (p=0.042). Although the results of this study do not support the influence of HMB supplementation on circulating concentrations of IGF-1 or IGFBPs1-6 during high intensity military training, it does present initial evidence that it may lower circulating IGFBP-7 concentrations. This may provide some indication of a reduced stress response, but further investigation

  7. [β-hydroxy-β-methylbutyrate as a dietary supplement (I): metabolism and toxicity].

    PubMed

    Manjarrez-Montes-de-Oca, Rafael; Torres-Vaca, Mateo; González-Gallego, Javier; Alvear-Ordenes, Ildefonso

    2014-11-27

    Introducción: El -hidroxi--metilbutirato (HMB) es un metabolito de la leucina producido a partir del ácido -cetoisocaproico. El HMB se utiliza como suplemento nutricional en el deporte desde 1997, atribuyéndosele una disminución de la proteólisis muscular. En los últimos años, se han descrito efectos positivos del HMB en diversas patologías, lo cual aumenta su probable utilidad para la mejora de la salud. Objetivos: Los objetivos de la presente revisión son: conocer el metabolismo del HMB, así como su absorción y excreción; estudiar la posible toxicidad del HMB; e identificar los mecanismos celulares y moleculares de acción del HMB cuando se utiliza como suplemento nutricional. Métodos: Se utilizaron las bases de datos Web of Science, Pubmed y SportDiscus para realizar la búsqueda de artículos. Los resultados se dividieron en dos partes; en este artículo se abordan el metabolismo y la posible toxicidad del HMB. Resultados: Diversos estudios relacionan al HMB con el metabolismo del colesterol en el músculo esquelético, probablemente reduciendo la proteólisis, a través del 3-hidroxi-3-metilglutaril-coenzima A, que se transforma a mevalonato, actuando como precursor en la síntesis de colesterol. Sin embargo, el HMB podría transformarse en beta-hidroxi-butirato a través del metabolismo del acetoacetato, por medio de la beta-hidroxibutirato dehidrogenasa. Por otra parte, la forma química más habitual en los suplementos nutricionales es la sal de calcio de HMB y la dosis más utilizada, de 3 g de HMB/día. Los estudios realizados en humanos y en animales muestran que no existen efectos adversos por el consumo de HMB. Conclusiones: Los efectos metabólicos y la ausencia de toxicidad del HMB lo hacen adecuado para su uso como suplemento nutricional.

  8. PIXE Analysis of Metal Hull Bolts From HMB DeBraak

    NASA Astrophysics Data System (ADS)

    Correll, Francis D.; Cole, Lord K.; Slater, Charles J.; Vanhoy, Jeffrey R.; Fithian, Charles H.

    2009-03-01

    HMB DeBraak was a 16-gun British brig-sloop that sank in a squall on May 25, 1798 off Cape Henlopen, Delaware. Silt covered the wooden hull shortly after it sank, preserving it until DeBraak was raised in 1986. The items recovered from the ship include metal bolts that held the hull together. We used PIXE to measure the compositions of 45 of the bolts and found that they are nearly pure copper (98.3% on average), with most also containing small amounts of iron (0.87%), nickel (0.039%), arsenic (0.43%), silver (0.089%), lead (0.18%), and bismuth (0.12%). A few contain a little indium, tin, or antimony, but none contain zinc above the quantization level. The compositions are similar to those reported for 18th-century English copper, but different from several copper alloys also used to make hull bolts. We conclude that, when DeBraak was last fitted out in 1795-1797, the Royal Navy was still using bolts similar to William Forbes's mechanically hardened pure copper bolts. Forbes's process represents the successful innovation and application of new technology in Royal Navy ships during the wars of the late 18th century.

  9. PIXE Analysis of Metal Hull Bolts From HMB DeBraak

    SciTech Connect

    Correll, Francis D.; Cole, Lord K.; Slater, Charles J.; Vanhoy, Jeffrey R.; Fithian, Charles H.

    2009-03-10

    HMB DeBraak was a 16-gun British brig-sloop that sank in a squall on May 25, 1798 off Cape Henlopen, Delaware. Silt covered the wooden hull shortly after it sank, preserving it until DeBraak was raised in 1986. The items recovered from the ship include metal bolts that held the hull together. We used PIXE to measure the compositions of 45 of the bolts and found that they are nearly pure copper (98.3% on average), with most also containing small amounts of iron (0.87%), nickel (0.039%), arsenic (0.43%), silver (0.089%), lead (0.18%), and bismuth (0.12%). A few contain a little indium, tin, or antimony, but none contain zinc above the quantization level. The compositions are similar to those reported for 18th-century English copper, but different from several copper alloys also used to make hull bolts. We conclude that, when DeBraak was last fitted out in 1795-1797, the Royal Navy was still using bolts similar to William Forbes's mechanically hardened pure copper bolts. Forbes's process represents the successful innovation and application of new technology in Royal Navy ships during the wars of the late 18th century.

  10. Effects of β-hydroxy-β-methylbutyrate (HMB) on skeletal muscle mitochondrial content and dynamics, and lipids after 10 days of bed rest in older adults.

    PubMed

    Standley, Robert A; Distefano, Giovanna; Pereira, Suzette L; Tian, Min; Kelly, Owen J; Coen, Paul M; Deutz, Nicolaas E P; Wolfe, Robert R; Goodpaster, Bret H

    2017-07-13

    Loss of muscle mass during periods of disuse likely has negative health consequences for older adults. We have previously shown that β-hydroxy-β-methylbutyrate (HMB) supplementation during 10 days of strict bed rest (BR) attenuates the loss of lean mass in older adults. To elucidate potential molecular mechanisms of HMB effects on muscle during bed rest and resistance training rehabilitation (RT), we examined mediators of skeletal muscle mitochondrial dynamics, autophagy and atrophy, and intramyocellular lipids. Nineteen older adults (60-76years) completed 10 days BR followed by 8 weeks RT rehabilitation. Subjects were randomized to either HMB(3g/d,HMB,n=11) or control(CON,n=8) groups. Skeletal muscle cross-sectional area (CSA) was determined by histology from percutaneous vastus lateralis biopsies. We measured protein markers of mitochondrial content (OXPHOS), fusion and fission (MFN2, OPA1, FIS1, DRP1), autophagy (Beclin1, LC3B, BNIP3), and atrophy (poly-ubiquinated proteins (poly-ub) by Western blot. Fatty acid composition of several lipid classes in skeletal muscle was measured by infusion-MS analysis. Poly-ub proteins and OXPHOS complex I increased in both groups following BR (P<0.05, main effect for time) and muscle triglyceride content tended to increase following BR in the HMB group (P=0.055). RT rehabilitation increased OXPHOS complex II protein (P<0.05), and total OXPHOS content tended (P=0.0504) to be higher in HMB group. In addition, higher levels of DRP1 and MFN2 were maintained in the HMB group after RT (P<0.05). BNIP3 and poly-ub proteins were significantly reduced following rehabilitation in both groups (P<0.05). Collectively, these data suggest that HMB influences mitochondrial dynamics and lipid metabolism during disuse atrophy and rehabilitation. Copyright © 2017, Journal of Applied Physiology.

  11. Effects of combined β-hydroxy-β-methylbutyrate (HMB) and whey protein ingestion on symptoms of eccentric exercise-induced muscle damage.

    PubMed

    Shirato, Minayuki; Tsuchiya, Yosuke; Sato, Teruyuki; Hamano, Saki; Gushiken, Takeshi; Kimura, Naoto; Ochi, Eisuke

    2016-01-01

    The purpose of this study was to examine the effects of combined β-hydroxy-β-methylbutyrate (HMB) and whey protein ingestion on muscle strength and damage following a single bout of eccentric exercise. Eighteen untrained male subjects were assigned to HMB and Whey protein (HMB + Whey; 3 g/day HMB and 36.6 g/day whey protein, n = 6), HMB (3 g/day, n = 6), or whey protein (36.6 g/day, n = 6) groups. Ingestion commenced 7 days before non-dominant elbow flexor eccentric exercise (30 deg/sec, 6 reps × 7 sets) and continued until 4 days post-exercise. The maximal isometric strength, muscle soreness, plasma creatine kinase (CK), lactate dehydrogenase (LDH) were assessed pre-exercise, and at 1, 2, 3, and 5 days after exercise. The change scores of maximal isometric strength significantly decreased at day 1, 2, and 5 in the whey protein group compared to pre value and that in HMB + Whey protein and HMB groups decreased at day 1 and 5. The muscle soreness significantly increased in the whey and HMB + Whey protein groups at day 3 compared to pre value (p < 0.05). CK and LDH significantly increased (time effect: p < 0.05) after exercise. However, all data were not significant difference among the groups. These results suggest that ingestion of combined HMB and whey protein does not have a role to inhibit muscle strength loss and soreness, and decrease in muscle damage markers after eccentric exercise in comparison with HMB and whey protein alone.

  12. Investigation into the Antigenic Properties and Contributions to Growth in Blood of the Meningococcal Haemoglobin Receptors, HpuAB and HmbR

    PubMed Central

    Bidmos, Fadil A.; Chan, Hannah; Praekelt, Uta; Tauseef, Isfahan; Ali, Youssif M.; Kaczmarski, Edward B.; Feavers, Ian; Bayliss, Christopher D.

    2015-01-01

    Acquisition of iron from host complexes is mediated by four surface-located receptors of Neisseria meningitidis. The HmbR protein and heterodimeric HpuAB complex bind to haemoglobin whilst TbpBA and LbpBA bind iron-loaded transferrin and lactoferrin complexes, respectively. The haemoglobin receptors are unevenly distributed; disease-causing meningococcal isolates encode HmbR or both receptors while strains with only HpuAB are rarely-associated with disease. Both these receptors are subject to phase variation and 70–90% of disease isolates have one or both of these receptors in an ON expression state. The surface-expression, ubiquity and association with disease indicate that these receptors could be potential virulence factors and vaccine targets. To test for a requirement during disease, an hmbR deletion mutant was constructed in a strain (MC58) lacking HpuAB and in both a wild-type and TbpBA deletion background. The hmbR mutant exhibited an identical growth pattern to wild-type in whole blood from healthy human donors whereas growth of the tbpBA mutant was impaired. These results suggest that transferrin is the major source of iron for N. meningitidis during replication in healthy human blood. To examine immune responses, polyclonal antisera were raised against His-tagged purified-recombinant variants of HmbR, HpuA and HpuB in mice using monolipopolysaccharide as an adjuvant. Additionally, monoclonal antibodies were raised against outer membrane loops of HmbR presented on the surface of EspA, an E. coli fimbrial protein. All antisera exhibited specific reactivity in Western blots but HmbR and HpuA polyclonal sera were reactive against intact meningococcal cells. None of the sera exhibited bactericidal activity against iron-induced wild-type meningococci. These findings suggest that the HmbR protein is not required during the early stages of disease and that immune responses against these receptors may not be protective. PMID:26208277

  13. Investigation into the Antigenic Properties and Contributions to Growth in Blood of the Meningococcal Haemoglobin Receptors, HpuAB and HmbR.

    PubMed

    Bidmos, Fadil A; Chan, Hannah; Praekelt, Uta; Tauseef, Isfahan; Ali, Youssif M; Kaczmarski, Edward B; Feavers, Ian; Bayliss, Christopher D

    2015-01-01

    Acquisition of iron from host complexes is mediated by four surface-located receptors of Neisseria meningitidis. The HmbR protein and heterodimeric HpuAB complex bind to haemoglobin whilst TbpBA and LbpBA bind iron-loaded transferrin and lactoferrin complexes, respectively. The haemoglobin receptors are unevenly distributed; disease-causing meningococcal isolates encode HmbR or both receptors while strains with only HpuAB are rarely-associated with disease. Both these receptors are subject to phase variation and 70-90% of disease isolates have one or both of these receptors in an ON expression state. The surface-expression, ubiquity and association with disease indicate that these receptors could be potential virulence factors and vaccine targets. To test for a requirement during disease, an hmbR deletion mutant was constructed in a strain (MC58) lacking HpuAB and in both a wild-type and TbpBA deletion background. The hmbR mutant exhibited an identical growth pattern to wild-type in whole blood from healthy human donors whereas growth of the tbpBA mutant was impaired. These results suggest that transferrin is the major source of iron for N. meningitidis during replication in healthy human blood. To examine immune responses, polyclonal antisera were raised against His-tagged purified-recombinant variants of HmbR, HpuA and HpuB in mice using monolipopolysaccharide as an adjuvant. Additionally, monoclonal antibodies were raised against outer membrane loops of HmbR presented on the surface of EspA, an E. coli fimbrial protein. All antisera exhibited specific reactivity in Western blots but HmbR and HpuA polyclonal sera were reactive against intact meningococcal cells. None of the sera exhibited bactericidal activity against iron-induced wild-type meningococci. These findings suggest that the HmbR protein is not required during the early stages of disease and that immune responses against these receptors may not be protective.

  14. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on the expression of ubiquitin ligases, protein synthesis pathways and contractile function in extensor digitorum longus (EDL) of fed and fasting rats.

    PubMed

    Gerlinger-Romero, Frederico; Guimarães-Ferreira, Lucas; Yonamine, Caio Yogi; Salgueiro, Rafael Barrera; Nunes, Maria Tereza

    2017-01-12

    Beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, enhances the gain of skeletal muscle mass by increasing protein synthesis or attenuating protein degradation or both. The aims of this study were to investigate the effect of HMB on molecular factors controlling skeletal muscle protein synthesis and degradation, as well as muscle contractile function, in fed and fasted conditions. Wistar rats were supplied daily with HMB (320 mg/kg body weight diluted in NaCl-0.9%) or vehicle only (control) by gavage for 28 days. After this period, some of the animals were subjected to a 24-h fasting, while others remained in the fed condition. The EDL muscle was then removed, weighed and used to evaluate the genes and proteins involved in protein synthesis (AKT/4E-BP1/S6) and degradation (Fbxo32 and Trim63). A sub-set of rats were used to measure in vivo muscle contractile function. HMB supplementation increased AKT phosphorylation during fasting (three-fold). In the fed condition, no differences were detected in atrogenes expression between control and HMB supplemented group; however, HMB supplementation did attenuate the fasting-induced increase in their expression levels. Fasting animals receiving HMB showed improved sustained tetanic contraction times (one-fold) and an increased muscle to tibia length ratio (1.3-fold), without any cross-sectional area changes. These results suggest that HMB supplementation under fasting conditions increases AKT phosphorylation and attenuates the increased of atrogenes expression, followed by a functional improvement and gain of skeletal muscle weight, suggesting that HMB protects skeletal muscle against the deleterious effects of fasting.

  15. Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults.

    PubMed

    Deutz, Nicolaas E P; Pereira, Suzette L; Hays, Nicholas P; Oliver, Jeffery S; Edens, Neile K; Evans, Chris M; Wolfe, Robert R

    2013-10-01

    Loss of muscle mass due to prolonged bed rest decreases functional capacity and increases hospital morbidity and mortality in older adults. To determine if HMB, a leucine metabolite, is capable of attenuating muscle decline in healthy older adults during complete bed rest. A randomized, controlled, double-blinded, parallel-group design study was carried out in 24 healthy (SPPB ≥ 9) older adult subjects (20 women, 4 men), confined to complete bed rest for ten days, followed by resistance training rehabilitation for eight weeks. Subjects in the experimental group were treated with HMB (calcium salt, 1.5 g twice daily - total 3 g/day). Control subjects were treated with an inactive placebo powder. Treatments were provided starting 5 days prior to bed rest till the end rehabilitation phase. DXA was used to measure body composition. Nineteen eligible older adults (BMI: 21-33; age: 60-76 year) were evaluable at the end of the bed rest period (Control n = 8; Ca-HMB n = 11). Bed rest caused a significant decrease in total lean body mass (LBM) (2.05 ± 0.66 kg; p = 0.02, paired t-test) in the Control group. With the exclusion of one subject, treatment with HMB prevented the decline in LBM over bed rest -0.17 ± 0.19 kg; p = 0.23, paired t-test). There was a statistically significant difference between treatment groups for change in LBM over bed rest (p = 0.02, ANOVA). Sub-analysis on female subjects (Control = 7, HMB = 8) also revealed a significant difference in change in LBM over bed rest between treatment groups (p = 0.04, ANOVA). However, differences in function parameters could not be observed, probably due to the sample size of the study. In healthy older adults, HMB supplementation preserves muscle mass during 10 days of bed rest. These results need to be confirmed in a larger trial. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  16. Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ.

    PubMed

    Kim, Jinah; Taube, Janis M; McCalmont, Timothy H; Glusac, Earl J

    2011-10-01

    It is often challenging to reliably assess the number of lesional melanocytes in intraepidermal melanocytic proliferations involving sun-damaged skin. Therefore, dermatopathologists routinely use immunostains to help differentiate melanocytes from surrounding keratinocytes. Forty-three cases of solar lentigo or melanoma in situ (of the lentigo maligna type) were retrospectively chosen (20 melanomas in situ and 23 solar lentigo). Microphthalmia transcription factor (MiTF), HMB-45, Melan-A and Mel-5 immunostains were performed with an Azure blue counterstain, and the mean melanocyte counts were calculated within a 1-mm segment of epidermis. In solar lentigines, the mean melanocyte counts were 27 (MiTF), 23 (HMB-45 and Mel-5) and 41 (Melan-A), as compared to hematoxylin and eosin (H&E) (25). In melanoma in situ, the mean melanocyte counts were 112 (MiTF), 149 (Melan-A), 111 (HMB-45) and 80 (Mel-5), as compared to H&E (109). These results show that Melan-A significantly overestimates the density of melanocytes within dermatoheliotic skin. Compared to other tested stains, nuclear staining MiTF allowed greater distinction of melanocytes from keratinocytes with melanized cytoplasm. These findings indicate that MiTF is a superior marker for quantification of melanocytes in the evaluation of subtle intraepidermal melanocytic proliferations and in the differential diagnosis of solar lentigo. Copyright © 2011 John Wiley & Sons A/S.

  17. Effect of Oral Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation on Physical Performance in Healthy Old Women Over 65 Years: An Open Label Randomized Controlled Trial

    PubMed Central

    Berton, Linda; Bano, Giulia; Carraro, Sara; Veronese, Nicola; Pizzato, Simona; Bolzetta, Francesco; De Rui, Marina; Valmorbida, Elena; De Ronch, Irene; Perissinotto, Egle; Coin, Alessandra; Manzato, Enzo; Sergi, Giuseppe

    2015-01-01

    Although older people are particularly liable to sarcopenia, limited research is available on beta-hydroxy-beta-methylbutyrate (HMB) supplementation in this population, particularly in healthy subjects. In this parallel-group, randomized, controlled, open-label trial, we aimed to evaluate whether an oral supplement containing 1.5 g of calcium HMB for 8 weeks could improve physical performance and muscle strength parameters in a group of community-dwelling healthy older women. Eighty healthy women attending a twice-weekly mild fitness program were divided into two equal groups of 40, and 32 of the treated women and 33 control completed the study. We considered a change in the Short Physical Performance Battery (SPPB) score as the primary outcome and changes in the peak torque (PT) isometric and isokinetic strength of the lower limbs, 6-minute walking test (6MWT), handgrip strength and endurance as secondary outcomes. Body composition was assessed with dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). The mean difference between the two groups on pre-post change were finally calculated (delta) for each outcome. After 8 weeks, there were no significant differences between the groups’ SPPB, handgrip strength or DXA parameters. The group treated with HMB scored significantly better than the control group for PT isokinetic flexion (delta = 1.56±1.56 Nm; p = 0.03) and extension (delta = 3.32±2.61 Nm; p = 0.03), PT isometric strength (delta = 9.74±3.90 Nm; p = 0.02), 6MWT (delta = 7.67±8.29 m; p = 0.04), handgrip endurance (delta = 21.41±16.28 s; p = 0.02), and muscle density assessed with pQCT. No serious adverse effects were reported in either group. In conclusion, a nutritional supplement containing 1.5 g of calcium HMB for 8 weeks in healthy elderly women had no significant effects on SPPB, but did significantly improve several muscle strength and physical performance parameters. Trial Registration Clinical

  18. Effect of Oral Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation on Physical Performance in Healthy Old Women Over 65 Years: An Open Label Randomized Controlled Trial.

    PubMed

    Berton, Linda; Bano, Giulia; Carraro, Sara; Veronese, Nicola; Pizzato, Simona; Bolzetta, Francesco; De Rui, Marina; Valmorbida, Elena; De Ronch, Irene; Perissinotto, Egle; Coin, Alessandra; Manzato, Enzo; Sergi, Giuseppe

    2015-01-01

    Although older people are particularly liable to sarcopenia, limited research is available on beta-hydroxy-beta-methylbutyrate (HMB) supplementation in this population, particularly in healthy subjects. In this parallel-group, randomized, controlled, open-label trial, we aimed to evaluate whether an oral supplement containing 1.5 g of calcium HMB for 8 weeks could improve physical performance and muscle strength parameters in a group of community-dwelling healthy older women. Eighty healthy women attending a twice-weekly mild fitness program were divided into two equal groups of 40, and 32 of the treated women and 33 control completed the study. We considered a change in the Short Physical Performance Battery (SPPB) score as the primary outcome and changes in the peak torque (PT) isometric and isokinetic strength of the lower limbs, 6-minute walking test (6MWT), handgrip strength and endurance as secondary outcomes. Body composition was assessed with dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). The mean difference between the two groups on pre-post change were finally calculated (delta) for each outcome. After 8 weeks, there were no significant differences between the groups’ SPPB, handgrip strength or DXA parameters. The group treated with HMB scored significantly better than the control group for PT isokinetic flexion (delta = 1.56±1.56 Nm; p = 0.03) and extension (delta = 3.32±2.61 Nm; p = 0.03), PT isometric strength (delta = 9.74±3.90 Nm; p = 0.02), 6MWT (delta = 7.67±8.29 m; p = 0.04), handgrip endurance (delta = 21.41±16.28 s; p = 0.02), and muscle density assessed with pQCT. No serious adverse effects were reported in either group. In conclusion, a nutritional supplement containing 1.5 g of calcium HMB for 8 weeks in healthy elderly women had no significant effects on SPPB, but did significantly improve several muscle strength and physical performance parameters. ClinicalTrials.gov NCT02118181.

  19. The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study.

    PubMed

    Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podgórski, Tomasz

    2017-07-14

    The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased (p = 0.049) with a simultaneous reduction of fat mass (p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold (p < 0.0001), threshold load (p = 0.017) and the threshold HR (p < 0.0001), as well as anaerobic peak power (p = 0.005), average power (p = 0.029), maximum speed (p < 0.001) and post-exercise lactate concentrations (p < 0.0001). However, when compared to the placebo, no differences were observed in blood marker levels. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic and anaerobic capacity in combat sports athletes.

  20. The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study

    PubMed Central

    Jeszka, Jan; Podgórski, Tomasz

    2017-01-01

    The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased (p = 0.049) with a simultaneous reduction of fat mass (p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold (p < 0.0001), threshold load (p = 0.017) and the threshold HR (p < 0.0001), as well as anaerobic peak power (p = 0.005), average power (p = 0.029), maximum speed (p < 0.001) and post-exercise lactate concentrations (p < 0.0001). However, when compared to the placebo, no differences were observed in blood marker levels. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic and anaerobic capacity in combat sports athletes. PMID:28708126

  1. Microwave photochemical reactor for the online oxidative decomposition of p-hydroxymercurybenzoate (pHMB)-tagged proteins and their determination by cold vapor generation-atomic fluorescence detection.

    PubMed

    Campanella, Beatrice; Rivera, Jose González; Ferrari, Carlo; Biagi, Simona; Onor, Massimo; D'Ulivo, Alessandro; Bramanti, Emilia

    2013-12-17

    A novel method is presented for the characterization and determination of thiolic proteins. After the labeling with p-hydroxymercurybenzoate, the pHMB-labeled proteins underwent on-line oxidation with a novel microwave (MW)/UV photochemical reactor, followed by cold vapor generation-atomic fluorescence spectrometry (CVG-AFS) detection. The MW/UV process led to the conversion of pHMB to Hg(II) with a yield of 89.0 ± 0.5% without using chemical oxidizing reagents and avoiding the use of toxic carcinogenic compounds. Hg(II) was reduced to Hg(0) in a knotted reaction coil with NaBH4 solution, stripped from the solution by an argon flow and detected. The chromatographic method for labeled thiolic peptides was linear in the 0.2-100 μmol L(-1) range, with a LOD as mercury of 57 nmol L(-1). This system has proven to be a useful interface for liquid chromatography coupled with CVG-AFS in the determination and characterization of thiolic proteins. This method has been applied to the determination of thiolic peptides after tryptic digestion of serum albumins from different species (human, bovine, rat, horse, and sheep).

  2. Oral supplement enriched in HMB combined with pulmonary rehabilitation improves body composition and health related quality of life in patients with bronchiectasis (Prospective, Randomised Study).

    PubMed

    Olveira, Gabriel; Olveira, Casilda; Doña, Esperanza; Palenque, Francisco Javier; Porras, Nuria; Dorado, Antonio; Godoy, Ana M; Rubio-Martínez, Elehazara; Rojo-Martínez, Gemma; Martín-Valero, Rocío

    2016-10-01

    Pulmonary Rehabilitation (PR) is recommended for bronchiectasis but there is no data about its effect on body composition. The aim of this study is to assess the effect of Pulmonary Rehabilitation (PR) for 12 weeks in normally-nourished non-cystic-fibrosis bronchiectasis patients compared with the effect of PR plus a hyperproteic oral nutritional supplement enriched with beta-hydroxy-beta-methylbutyrate (HMB) on body composition, muscle strength, quality of life and serum biomarkers. single center randomized controlled trial, parallel treatment design: Participants were randomly assigned to receive PR for 12 weeks or PR plus ONS (PRONS) (one can per day). Outcome assessments were performed at baseline, 12 weeks and 24 weeks: body composition (Dual-energy X-Ray Absorptiometry (DEXA), mid-arm muscle circumference (MAMC), phase angle by Bio-impedance), health related quality of life (Spanish QOL-B-V3.0, Physical Functioning Scale), handgrip strength, diet questionnaire, and plasma levels of prealbumin, myostatin and somatomedin-c. Thirty patients were randomized (15 per group) without differences in clinical and respiratory variables. In the PRONS group bone mineral density (BMD), mean and maximum handgrip dynamometry, MAMC, QOLB and prealbumin were significantly increased from baseline at 12 and 24 weeks and Fat free Mass (FFM) and FFM index, at 12 weeks. In the PR group only mean handgrip dynamometry and prealbumin were significantly increased at 12 and 24 weeks. In both groups plasma myostatin was reduced at 12 weeks (without significant differences). The addition of a hyperproteic ONS enriched with HMB to Pulmonary Rehabilitation could improve body composition, BMD, muscle strength and health related quality of life in bronchiectasis patients. Clinical Trials Number NCT02048397. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  3. L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy

    PubMed Central

    2014-01-01

    Background The purpose of this study was to examine if L-leucine (Leu), β-hydroxy-β-methylbutyrate (HMB), or creatine monohydrate (Crea) prevented potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes. Methods After four days of differentiation, myotubes were treated with MSTN (10 ng/ml) for two additional days and four treatment groups were studied: 1) 3x per day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea, 4) DM only. Myotubes treated with DM without MSTN were analyzed as the control condition (DM/CTL). Following treatment, cells were analyzed for total protein, DNA content, RNA content, muscle protein synthesis (MPS, SUnSET method), and fiber diameter. Separate batch treatments were analyzed for mRNA expression patterns of myostatin-related genes (Akirin-1/Mighty, Notch-1, Ski, MyoD) as well as atrogenes (MuRF-1, and MAFbx/Atrogin-1). Results MSTN decreased fiber diameter approximately 30% compared to DM/CTL myotubes (p < 0.001). Leu, HMB and Crea prevented MSTN-induced atrophy. MSTN did not decrease MPS levels compared to DM/CTL myotubes, but MSTN treatment decreased the mRNA expression of Akirin-1/Mighty by 27% (p < 0.001) and MyoD by 26% (p < 0.01) compared to DM/CTL myotubes. shRNA experiments confirmed that Mighty mRNA knockdown reduced myotube size, linking MSTN treatment to atrophy independent of MPS. Remarkably, MSTN + Leu and MSTN + HMB myotubes had similar Akirin-1/Mighty and MyoD mRNA levels compared to DM/CTL myotubes. Furthermore, MSTN + Crea myotubes exhibited a 36% (p < 0.05) and 86% (p < 0.001) increase in Akirin-1/Mighty mRNA compared to DM/CTL and MSTN-only treated myotubes, respectively. Conclusions Leu, HMB and Crea may reduce MSTN-induced muscle fiber atrophy by influencing Akirin-1/Mighty mRNA expression patterns. Future studies are needed to examine if Leu, HMB and Crea independently or synergistically affect Akirin-1/Mighty expression, and how Akirin-1/Mighty

  4. Effects of combined maternal administration with alpha-ketoglutarate (AKG) and β-hydroxy-β-methylbutyrate (HMB) on prenatal programming of skeletal properties in the offspring

    PubMed Central

    2012-01-01

    Background Nutritional manipulations during fetal growth may induce long-term metabolic effects in postnatal life. The aim of the study was to test whether combined treatment of pregnant sows with alpha-ketoglutarate and β-hydroxy-β-methylbutyrate induces additive long-term effects on skeletal system properties in the offspring. Methods The study was performed on 290 pigs obtained from 24 sows divided into 4 equal groups and subjected to experimental treatment during two weeks before delivery. The first group consisted of control sows, while the second group received alpha-ketoglutarate. The third group was treated with β-hydroxy-β-methylbutyrate and the fourth group underwent combined administration of alpha-ketoglutarate and β-hydroxy-β-methylbutyrate. Piglets obtained from sows were reared until slaughter age to perform morphometric, densitometric and mechanical analyses of femur. Serum evaluations of growth hormone, insulin-like growth factor-1, bone-specific alkaline phosphatase and osteocalcin were performed in newborns and 90-day old piglets; additionally, plasma amino acid concentration was measured in newborns. Results Maternal treatment with alpha-ketoglutarate and β-hydroxy-β-methylbutyrate significantly reduced fattening time and increased birth body weight, daily body weight gain, bone weight, volumetric bone mineral density, geometrical parameters and mechanical endurance of femur. These effects were associated with increased serum concentrations of growth hormone, insulin-like growth factor-1, bone-specific alkaline phosphatase and osteocalcin. Furthermore, alpha-ketoglutarate and β-hydroxy-β-methylbutyrate administered solely or in combination significantly increased plasma level of 19 amino acids. Conclusions Hormonal and amino acid evaluations in pigs indicate additive effects of AKG and HMB on systemic growth and development; however, determination of bone properties has not shown such phenomenon. PMID:22578071

  5. [β-hydroxy-β-methylbutyrate as a dietary supplement (II): cell and molecular mechanism of action].

    PubMed

    Manjarrez-Montes-de-Oca, Rafael; Torres-Vaca, Mateo; González-Gallego, Javier; Alvear-Ordenes, Ildefonso

    2014-11-27

    Introducción: En los últimos años el -hidroxi--metilbutirato (HMB) ha sido foco de diversas investigaciones que le atribuyen un efecto sobre la disminución de la proteólisis muscular y un incremento de la masa muscular. Por tanto, se han realizado estudios centrados en los mecanismos celulares y moleculares responsables de dichos efectos. Objetivos: Los objetivos de la presente revisión son: conocer el metabolismo del HMB, así como su absorción y excreción; estudiar la posible toxicidad del HMB; e identificar los mecanismos celulares y moleculares de acción del HMB cuando se utiliza como suplemento nutricional. Métodos: Se utilizaron las bases de datos Web of Science, Pubmed y SportDiscus para realizar la búsqueda de artículos. Los resultados se dividieron en dos partes; en este artículo se presentan los resultados referentes a los mecanismos de acción del HMB. Resultados: No existen suficientes datos que apoyen que la ingesta de HMB incremente la síntesis de colesterol en el músculo. Es posible que existan efectos positivos en el metabolismo muscular a través de la vía mTOR y del sistema ubiquitin-proteasoma, aunque no se conoce su mecanismo de acción. Probablemente, el HMB eleva los niveles sanguíneos de hidroxibutirato y esto podría explicar sus principales efectos sobre la disminución de la proteólisis muscular. Conclusiones: De acuerdo a nuestros resultados, la posibilidad de justificar la acción del HMB a través de la vía del beta-hidroxibutirato abre una interesante línea de investigación para futuros estudios.

  6. PubMed

    Santesteban Moriones, Virginia; Ibáñez Santos, Javier

    2017-02-01

    Introducción: muy pocos suplementos nutricionales han demostrado científicamente su eficacia como ayuda ergogénica. Esta revisión analizará el monohidrato de creatina (MC), el β-hidroxi-β-metilbutirato (HMB), el bicarbonato sódico (BS), la β-alanina y la cafeína.Objetivos: analizar la eficacia, mecanismos de acción, dosis, efectos adversos y algunos deportes que se pueden beneficiar de su consumo.Métodos: búsqueda en la base de datos PubMed de revisiones bibliográficas de los últimos 15 años y artículos originales de los últimos 5 años de las sustancias estudiadas.Resultados: dosis de MC de 20 g/día durante 4-7 días son eficaces para mejorar la fuerza y la potencia muscular y el rendimiento en sprints cortos y repetidos. El HMB en dosis de 3 g/día durante un mínimo de 2 semanas contribuye al aumento de la masa magra y de la masa libre de grasa. La ingesta de 0,3 g/kg de BS mejora el rendimiento en pruebas de 400-1.500 m de atletismo y en sprintsintermitentes. Por su parte, dosis de 80 mg/kg/día de β-alanina durante 4-10 semanas pueden mejorar el rendimiento en ejercicios intermitentes de alta intensidad. Finalmente, la cafeína en dosis de 2 mg/kg mejora la capacidad de reacción y en dosis de 3-6 mg/kg mejora el rendimiento en pruebas de resistencia aeróbica.Conclusiones: los suplementos revisados presentan una demostrada eficacia en el rendimiento físico, pero hay que tener en cuenta que la mayoría de los estudios se han realizado con deportistas de nivel recreativo. Generalmente, la mejora del rendimiento físico con estos suplementos es menor cuanto mejor es el nivel deportivo del individuo; sin embargo, un incremento de apenas un 1% permite a veces avanzar varios puestos en una final. Finalmente, se debe llamar la atención sobre la importancia de optimizar la alimentación antes de plantearse la introducción de suplementos deportivos, especialmente en niños y jóvenes. Las sustancias que hemos analizado poseen una base cient

  7. Hypersensitivity to Mosquito Bites Associated with Natural Killer Cell–derived Large Granular Lymphocyte Lymphocytosis: A Case Report in Korea

    PubMed Central

    Chung, Joo Seop; Shin, Ho Jin; Lee, Eun Yup; Cho, Goon Jae

    2003-01-01

    Hypersensitivity to mosquito bites (HMB) is characterized by intense skin reactions at bite sites. The pathogenesis of HMB might be related to clonal lymphoproliferation of Epstein-Barr virus DNA-positive natural killer (NK) cells. We report the first case of HMB possibly associated with NK cell-derived large granular lymphocyte (NK-LGL) lymphocytosis in Korea. PMID:12760269

  8. Effect of Beta-Hydroxy Beta-Methylbutyrate on the Onset of Blood Lactate Accumulation and VO2peak in Endurance-Trained Cyclists.

    ERIC Educational Resources Information Center

    Vukovich, Matthew D.; Dreifort, Geri D.

    2001-01-01

    Examined the effect of beta-hydroxy beta-methylbutyrate (HMB) supplementation on maximal oxygen consumption (VO2peak) and onset of blood lactate accumulation (OBLA) in endurance-trained cyclists. Acute exercise did not affect plasma HMB concentrations. OBLA increased with HMB and leucine, with blood glucose significantly greater during the HMB…

  9. Effect of Beta-Hydroxy Beta-Methylbutyrate on the Onset of Blood Lactate Accumulation and VO2peak in Endurance-Trained Cyclists.

    ERIC Educational Resources Information Center

    Vukovich, Matthew D.; Dreifort, Geri D.

    2001-01-01

    Examined the effect of beta-hydroxy beta-methylbutyrate (HMB) supplementation on maximal oxygen consumption (VO2peak) and onset of blood lactate accumulation (OBLA) in endurance-trained cyclists. Acute exercise did not affect plasma HMB concentrations. OBLA increased with HMB and leucine, with blood glucose significantly greater during the HMB…

  10. Beta‐hydroxy‐beta‐methylbutyrate supplementation and skeletal muscle in healthy and muscle‐wasting conditions

    PubMed Central

    2017-01-01

    Abstract Beta‐hydroxy‐beta‐methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease. The data presented here indicate that the beneficial effects of HMB have been well characterized in strength‐power and endurance exercise. HMB attenuates exercise‐induced muscle damage and enhances muscle hypertrophy and strength, aerobic performance, resistance to fatigue, and regenerative capacity. HMB is particularly effective in untrained individuals who are exposed to strenuous exercise and in trained individuals who are exposed to periods of high physical stress. The low effectiveness of HMB in strength‐trained athletes could be due to the suppression of the proteolysis that is induced by the adaptation to training, which may blunt the effects of HMB. Studies performed with older people have demonstrated that HMB can attenuate the development of sarcopenia in elderly subjects and that the optimal effects of HMB on muscle growth and strength occur when it is combined with exercise. Studies performed under in vitro conditions and in various animal models suggest that HMB may be effective in treatment of muscle wasting in various forms of cachexia. However, there are few clinical reports of the effects of HMB on muscle wasting in cachexia; in addition, most of these studies evaluated the therapeutic potential of combinations of various agents. Therefore, it has not been possible to determine whether HMB was effective or if there was a synergistic effect. Although most of the endogenous HMB is produced in the liver, there are no reports regarding the levels and the effects of HMB supplementation

  11. Effects of β-hydroxy-β-methylbutyrate free acid and cold water immersion on post-exercise markers of muscle damage.

    PubMed

    Gonzalez, Adam M; Stout, Jeffrey R; Jajtner, Adam R; Townsend, Jeremy R; Wells, Adam J; Beyer, Kyle S; Boone, Carleigh H; Pruna, Gabriel J; Mangine, Gerald T; Scanlon, Tyler M; Bohner, Jonathan D; Oliveira, Leonardo P; Fragala, Maren S; Hoffman, Jay R

    2014-06-01

    The aim of the current study was to examine the effects of cold water immersion (CWI) with and without the free acid form of β-hydroxy-β-methylbutyrate (HMB-FA) on markers of muscle damage following acute lower body resistance exercise. Forty recreationally resistance-trained men (22.3 ± 2.4 years) were randomly divided into one of the four groups: (1) Placebo (PL); (2) HMB-FA; (3) HMB-FA-CWI; (4) PL-CWI. HMB-FA groups ingested 3 g day(-1) and CWI groups submersed their lower body into 10-12 °C water for 10-min post-exercise. No differences between groups were observed for CK; however, PL-CWI had significantly greater elevations in myoglobin 30-min post-exercise compared to HMB-FA (p = 0.009) and PL (p = 0.005), and HMB-FA-CWI was significantly greater than HMB-FA (p = 0.046) and PL (p = 0.028). No differences between groups were observed for IL-6 and IL-10, although CRP was significantly greater 24-h post-exercise for PL-CWI compared to HMB-FA-CWI (p = 0.02) and HMB-FA (p = 0.046). Only HMB-FA-CWI showed significantly (p = 0.02) greater improvements in average power per repetition. CWI appeared to elevate myoglobin compared to other groups, while HMB-FA may have attenuated the increase in CRP when combined with CWI. Nevertheless, HMB-FA or CWI treatments did not appear to provide benefit over PL for recovery. Instead, the combination of CWI and HMB-FA improved performance recovery compared to other groups.

  12. Hydroxy methoxy benzaldehyde from Sesbania grandilfora inhibits the advanced glycation end products (AGEs)-mediated fibrillation in hemoglobin.

    PubMed

    Prasanna, G; Hari, N; Saraswathi, N T

    2017-03-20

    The present study was aimed to identify the active anti-glycation constituent from the leaves of Sesbania grandiflora. Characterization of the active constituent resulted in the identification of hydroxy methoxy benzaldehyde (HMB). The potential of HMB as anti-glycation lead was analyzed by fluorescence spectroscopy, fluorescence microscopy, scanning electron microscopy (SEM) and molecular interaction studies. Our results suggested that HMB inhibited formation of early (HbA1c) and advanced glycation end products (AGEs). The amyloid-like fibrillation in hemoglobin was also inhibited by HMB. SEM images indicated the protective effect against the formation of acanthocytes. Molecular docking studies showed that HMB was interacting with hemoglobin through hydrogen bonds with Arg141, Tyr140, and Thr137. Our findings suggest that HMB could be a better anti-glycation lead molecule towards novel AGEs inhibitors.

  13. Na+-independent and nonstereospecific transport of 2-hydroxy 4-methylthiobutanoic acid by brush border membrane vesicles from chick small intestine.

    PubMed

    Brachet, P; Puigserver, A

    1989-01-01

    1. The transport of L- and DL-2-hydroxy 4-methylthiobutanoic acid (HMB), the methionine hydroxy analogue, by brush border membrane vesicles (BBMV) from chick small intestine was the sum of a saturable Michaelian component and a diffusive term. 2. Unlike that of L- and DL-MET, uptake was Na+-independent and electroneutral. 3. The inhibition of L-HMB transport by L-lactate, a structural analogue, and D-HMB as well, was of the competitive type. 4. Preloading of BBMV with D-HMB but not with L-lactate or L-MET trans-stimulated the influx of labelled L-HMB. 5. HMB uptake by rat and chick intestinal BBMV exhibited similar characteristics but the chick nonstereospecific transport system appeared to be unable to carry out L-lactate translocation.

  14. A case of hypersensitivity to mosquito bites without peripheral natural killer cell lymphocytosis in a 6-year-old Korean boy.

    PubMed

    Seon, Han-Su; Roh, Ji-Hyeon; Lee, Seung-Ho; Kang, Eun-Kyeong

    2013-01-01

    Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by intense skin reactions such as bulla and necrotic ulcerations at bite sites, accompanied by general symptoms such as high-grade fever and malaise occurred after mosquito bites. It has been suggested that HMB is associated with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukemia/lymphoma. We describe here a Korean child who presented with 3-yr history of HMB without natural killer cell lymphocytosis. He has been ill for 6 yr with HMB. Close observation and examination for the development of lymphoproliferative status or hematologic malignant disorders is needed.

  15. Reduced Transforming Growth Factor-β Activity in the Endometrium of Women With Heavy Menstrual Bleeding.

    PubMed

    Maybin, Jacqueline A; Boswell, Lyndsey; Young, Vicky J; Duncan, William C; Critchley, Hilary O D

    2017-04-01

    Heavy menstrual bleeding (HMB) is common and incapacitating. Aberrant menstrual endometrial repair may result in HMB. The transforming growth factor (TGF)-β superfamily contributes to tissue repair, but its role in HMB is unknown. We hypothesized that TGF-β1 is important for endometrial repair, and women with HMB have aberrant TGF-β1 activity at menses. Endometrial biopsies were collected from women, and menstrual blood loss objectively measured [HMB >80 mL/cycle; normal menstrual bleeding (NMB) <80 mL]. Immunohistochemistry and reverse transcription polymerase chain reaction examined endometrial TGF-β1 ligand, receptors, and downstream SMADs in women with NMB and HMB. The function and regulation of TGF-β1 were examined using cell culture. TGFB1 mRNA was maximal immediately prior to menses, but no differences detected between women with NMB and HMB at any cycle stage. Histoscoring of TGFB1 revealed reduced staining in the stroma during menses in women with HMB (P < 0.05). There were no significant differences in TGFBR1/2 or TGFBR1/2 immunostaining. Cortisol increased activation of TGFB1 in the supernatant of human endometrial stromal cells (HES; P < 0.05) via thrombospondin-1. Endometrial SMAD2 and SMAD3 were lower in women with HMB during menstruation (P < 0.05), and decreased phosphorylated SMAD2/3 immunostaining was seen in glandular epithelial cells during the late secretory phase (P < 0.05). Wound scratch assays revealed increased repair in HES cells treated with TGF-β1 versus control (P < 0.05). Women with HMB had decreased TGF-β1 and SMADs perimenstrually. Cortisol activated latent TGF-β1 to enhance endometrial stromal cell repair. Decreased TGF-β1 activity may hinder repair of the denuded menstrual endometrium, resulting in HMB.

  16. Peak Performance Through Nutrition and Exercise

    DTIC Science & Technology

    1999-09-01

    HMB), Chromium Picolinate No benefits demonstrated for many in this class. For HMB and chromium the research is inconclusive. Some may cause nausea...vomiting, cramps, and anemia. Chromium may cause DNA damage. Growth Hormone (GH) Releasers Arginine, Lysine, Ornithine, Branched chain Amino Acids

  17. Knowledge of Latin American Obstetricians and Gynecologists regarding Heavy Menstrual Bleeding

    PubMed Central

    Marin, Victor; Ciarmatori, Silvia; Silva-Filho, Agnaldo L.; Acuña, Juan Manuel; Makuch, Maria Y.

    2016-01-01

    Background. Heavy menstrual bleeding (HMB) is a common gynecological complaint affecting quality of life. Objectives. To assess knowledge on diagnosis and treatments of HMB of Latin American (LA) obstetricians and gynecologists (OBGYNs). Methods. A survey was conducted during a scientific meeting, organized to provide updated information on topics of reproductive medicine to OBGYNs from 12 LA countries who were invited to respond to a multiple-choice questionnaire. Results. Of the 210 OBGYNs participating in the survey, from 169 (80.4%) to 203 (96.7%) answered the questions. Most respondents (80%) gave accurate answers regarding the amount of blood loss which defines HMB, underreported the proportion of women who consulted due to HMB, and were aware that the use of combined oral contraceptives (COCs) with ethynyl estradiol is not an adequate treatment in women with HMB. Female OBGYNs and those who worked in the private sector were more prone to report a higher possibility of improvement of HMB with a COC that contained estradiol valerate and dienogest or with a levonorgestrel-releasing intrauterine system. Conclusions. In general, the respondents were aware of the importance of HMB in gynecological practice and of the new medical treatments and underreported the proportion of women who consulted due to HMB. PMID:27648073

  18. Improving the cardio protective effect of aFGF in ischemic myocardium with ultrasound-mediated cavitation of heparin modified microbubbles: preliminary experiment.

    PubMed

    Zhao, Ying-Zheng; Lu, Cui-Tao; Li, Xiao-Kun; Tang, Qin-Qin; Tian, Xin-Qiao; Zhao, Ya-Ping; Zhang, Yan; Tian, Ji-Lai; Yang, Wei; Ge, Shuping; Nair, Chandra K; Shen, Xuedong

    2012-08-01

    Ultrasound (US)-mediated cavitation of microbubbles has evolved into a new tool for organ-specific gene and drug delivery. This paper was to investigate the feasibility of acidic fibroblast growth factor (aFGF) intravenous delivery to the ischemic myocardium of rats by ultrasonic microbubbles modified with heparin. Heparin modified microbubbles (HMB) were prepared by the freeze-dried method. Acute myocardial infarction (AMI) model was established and the cardio protective effect of the aFGF combing with HMB (aFGF-HMB) under US-mediated cavitation technique was investigated. aFGF-HMB combined with US-mediated cavitation technique was examined by ECG. Ejection fraction (EF), fractional shortening (FS) and left ventricular diastolic diameter (LVDd) were measured to monitor the improvement of global myocardial contractile function. Myocardial tissue was stained with hematoxylin and eosine (HE) to evaluate the elaborate general morphology of the ischemic myocardium. From morphologic observation and echocardiography in rat heart, aFGF-HMB had suitable size distribution, physical stability and good acoustic resonance function. From AMI rat experiments, aFGF-HMB under US-mediated cavitation technique exerted aFGF cardio protective effect in ischemic myocardium. From histological evaluation, US-mediated cavitation of aFGF-HMB showed improvement of myocardial ischemia. With the visual imaging and US-triggered drug release advantages, US-mediated cavitation of aFGF-HMB might be developed as a novel technique for targeting delivery of aFGF into ischemic myocardium.

  19. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of beta-hydroxy-beta-methylbutyrate

    USDA-ARS?s Scientific Manuscript database

    Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB). To determine the effects of HMB on protein synthesis and ...

  20. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of beta-hydroxy-beta-methylbutyrate

    USDA-ARS?s Scientific Manuscript database

    Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB). To determine the effects of HMB on protein synthesi...

  1. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of Beta-hydroxy-Beta-methylbutyrate

    USDA-ARS?s Scientific Manuscript database

    Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite Beta-hydroxy-Beta-methylbutyrate (HMB). To determine the effects of HMB on protein synthesi...

  2. Knowledge of Latin American Obstetricians and Gynecologists regarding Heavy Menstrual Bleeding.

    PubMed

    Bahamondes, Luis; Marin, Victor; Ciarmatori, Silvia; Silva-Filho, Agnaldo L; Acuña, Juan Manuel; Makuch, Maria Y

    2016-01-01

    Background. Heavy menstrual bleeding (HMB) is a common gynecological complaint affecting quality of life. Objectives. To assess knowledge on diagnosis and treatments of HMB of Latin American (LA) obstetricians and gynecologists (OBGYNs). Methods. A survey was conducted during a scientific meeting, organized to provide updated information on topics of reproductive medicine to OBGYNs from 12 LA countries who were invited to respond to a multiple-choice questionnaire. Results. Of the 210 OBGYNs participating in the survey, from 169 (80.4%) to 203 (96.7%) answered the questions. Most respondents (80%) gave accurate answers regarding the amount of blood loss which defines HMB, underreported the proportion of women who consulted due to HMB, and were aware that the use of combined oral contraceptives (COCs) with ethynyl estradiol is not an adequate treatment in women with HMB. Female OBGYNs and those who worked in the private sector were more prone to report a higher possibility of improvement of HMB with a COC that contained estradiol valerate and dienogest or with a levonorgestrel-releasing intrauterine system. Conclusions. In general, the respondents were aware of the importance of HMB in gynecological practice and of the new medical treatments and underreported the proportion of women who consulted due to HMB.

  3. Treatment of Women With an Endometrial Polyp and Heavy Menstrual Bleeding: A Levonorgestrel-Releasing Intrauterine Device or Hysteroscopic Polypectomy?

    PubMed

    van Dijk, Myrthe M; van Hanegem, Nehalennia; de Lange, Maria E; Timmermans, Anne

    2015-01-01

    We performed a literature review of reports comparing a levonorgestrel-releasing intrauterine device (LNG-IUD) with transcervical polyp resection (TCRP) as a treatment for heavy menstrual bleeding (HMB). Our second objective was to investigate the effectiveness of LNG-IUD and TCRP in reducing menstrual bleeding and the patient satisfaction with each technique. No previously reported studies have compared TCRP and LNG-IUD as treatment for HMB in premenopausal women with an endometrial polyp. Likewise, no studies are available on LNG-IUD as a treatment for HMB in the presence of an endometrial polyp. Several studies have found the LNG-IUD to be an effective treatment option for HMB, with high patient satisfaction rates. Evidence of the effectiveness of TCRP as treatment of HMB is scarce. Patient satisfaction is reported relatively good, although persistent or recurrent symptoms appear to be frequent. We conclude that no evidence is available on LNG-IUD as treatment for HMB in women with an endometrial polyp. We hypothesize that LNG-IUD could be a good alternative to TCRP for treating HMB in premenopausal women with a polyp; however, further evidence is needed, and a randomized controlled trial should be performed. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

  4. Downregulation of miR-150 Expression by DNA Hypermethylation Is Associated with High 2-Hydroxy-(4-methylthio)butanoic Acid-Induced Hepatic Cholesterol Accumulation in Nursery Piglets.

    PubMed

    Jia, Yimin; Ling, Mingfa; Zhang, Luchu; Jiang, Shuxia; Sha, Yusheng; Zhao, Ruqian

    2016-10-12

    Excess 2-hydroxy-(4-methylthio)butanoic acid (HMB) supplementation induces hyperhomocysteinemia, which contributes to hepatic cholesterol accumulation. However, it is unclear whether and how high levels of HMB break hepatic cholesterol homeostasis in nursery piglets. In this study, HMB oversupplementation suppressed food intake and decreased body weight in nursery piglets. Hyperhomocysteinemia and higher hepatic cholesterol accumulation were observed in HMB groups. Accordingly, HMB significantly increased the protein content of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and glycine N-methyltransferase (GNMT) but decreased that of acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1). Significant downregulation of miR-150, miR-181d-5p, and miR-296-3p targeting the 3'-untranslated regions (UTRs) of GNMT and HMGCR was detected in the liver of HMB-treated piglets, and their functional validation was confirmed by dual-luciferase reporter assay. Furthermore, hypermethylation of miR-150 promoter was detected in association with suppressed miR-150 expression in the livers of HMB-treated piglets. This study indicated a new mechanism of hepatic cholesterol unhomeostasis by dietary methyl donor supplementation.

  5. Acute β-Hydroxy-β-Methyl Butyrate Suppresses Regulators of Mitochondrial Biogenesis and Lipid Oxidation While Increasing Lipid Content in Myotubes.

    PubMed

    Schnuck, Jamie K; Johnson, Michele A; Gould, Lacey M; Gannon, Nicholas P; Vaughan, Roger A

    2016-10-01

    Leucine modulates synthetic and degradative pathways in muscle, possibly providing metabolic benefits for both athletes and diseased populations. Leucine has become popular among athletes for improving performance and body composition, however little is known about the metabolic effects of the commonly consumed leucine-derived metabolite β-hydroxy-β-methyl butyrate (HMB). Our work measured the effects of HMB on metabolic protein expression, mitochondrial content and metabolism, as well as lipid content in skeletal muscle cells. Specifically, cultured C2C12 myotubes were treated with either a control or HMB ranging from 6.25 to 25 μM for 24 h and mRNA and/or protein expression, oxygen consumption, glucose uptake, and lipid content were measured. Contrary to leucine's stimulatory effect on metabolism, HMB-treated cells exhibited significantly reduced regulators of lipid oxidation including peroxisome proliferator-activated receptor alpha (PPARα) and PPARβ/δ, as well as downstream target carnitine palmitoyl transferase, without alterations in glucose or palmitate oxidation. Furthermore, HMB significantly inhibited activation of the master regulator of energetics, AMP-activated protein kinase. As a result, HMB-treated cells also displayed reduced total mitochondrial content compared with true control or cells equivocally treated with leucine. Additionally, HMB treatment amplified markers of lipid biosynthesis (PPARγ and fatty acid synthase) as well as consistently promoted elevated total lipid content versus control cells. Collectively, our results demonstrate that HMB did not improve mitochondrial metabolism or content, and may promote elevated cellular lipid content possibly through heightened PPARγ expression. These observations suggest that HMB may be most beneficial for populations interested in stimulating anabolic cellular processes.

  6. Effects of addition of Aspergillus oryzae culture and 2-hydroxyl-4-(methylthio) butanoic acid on milk performance and rumen fermentation of dairy cows.

    PubMed

    Sun, Hua; Wu, Yueming; Wang, Yanming; Wang, Chong; Liu, Jianxin

    2017-04-01

    To investigate effects of Aspergillus oryzae culture (AOC) and 2-hydroxy-4-(methylthio) butanoic acid (HMB) on milk performance and rumen fermentation of dairy cows. Sixty-four multiparous Chinese Holstein cows were randomly allocated into four experimental diets: (i) Control diet; (ii) AOC diet: 5 g AOC/day per head; (iii) HMB diet: 25 g HMB/day; and (iv) AH diet: 5 g AOC plus 25 g HMB/day. Added HMB tended to increase the yield of milk protein (P = 0.06) and 3.5% fat-corrected milk (P = 0.08) and milk fat content (P = 0.09). Milk fat yield (P = 0.03) and the contents of milk protein (P = 0.05) were increased by adding HMB. The cows fed on AOC diet had a tendency for higher body weight (BW) gain (P = 0.08). Addition of AOC, HMB and AH increased content of microbial protein (MCP) and total volatile fatty acids (VFA) (P < 0.01) in rumen fluid. Populations of rumen fungi, Fibrobacter succinogenes and Ruminococcus flavefaciens relative to total bacterial 16S rDNA (P ≤ 0.03) and activity of carboxymethylcellulase (CMCase) (P < 0.01) were increased with added AOC or HMB. It is inferred that added AOC or HMB can increase the contents of MCP and total VFA potentially by stimulating rumen microbe populations and CMCase activity. © 2016 Japanese Society of Animal Science.

  7. β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats

    PubMed Central

    Hao, Yanlei; Jackson, Janna R.; Wang, Yan; Edens, Neile; Pereira, Suzette L.

    2011-01-01

    β-Hydroxy-β-methylbutyrate (HMB) is a leucine metabolite shown to reduce protein catabolism in disease states and promote skeletal muscle hypertrophy in response to loading exercise. In this study, we evaluated the efficacy of HMB to reduce muscle wasting and promote muscle recovery following disuse in aged animals. Fisher 344×Brown Norway rats, 34 mo of age, were randomly assigned to receive either Ca-HMB (340 mg/kg body wt) or the water vehicle by gavage (n = 32/group). The animals received either 14 days of hindlimb suspension (HS, n = 8/diet group) or 14 days of unloading followed by 14 days of reloading (R; n = 8/diet group). Nonsuspended control animals were compared with suspended animals after 14 days of HS (n = 8) or after R (n = 8). HMB treatment prevented the decline in maximal in vivo isometric force output after 2 wk of recovery from hindlimb unloading. The HMB-treated animals had significantly greater plantaris and soleus fiber cross-sectional area compared with the vehicle-treated animals. HMB decreased the amount of TUNEL-positive nuclei in reloaded plantaris muscles (5.1% vs. 1.6%, P < 0.05) and soleus muscles (3.9% vs. 1.8%, P < 0.05). Although HMB did not significantly alter Bcl-2 protein abundance compared with vehicle treatment, HMB decreased Bax protein abundance following R, by 40% and 14% (P < 0.05) in plantaris and soleus muscles, respectively. Cleaved caspase-3 was reduced by 12% and 9% (P < 0.05) in HMB-treated reloaded plantaris and soleus muscles, compared with vehicle-treated animals. HMB reduced cleaved caspase-9 by 14% and 30% (P < 0.05) in reloaded plantaris and soleus muscles, respectively, compared with vehicle-treated animals. Although, HMB was unable to prevent unloading-induced atrophy, it attenuated the decrease in fiber area in fast and slow muscles after HS and R. HMB's ability to protect against muscle loss may be due in part to putative inhibition of myonuclear apoptosis via regulation of mitochondrial

  8. A Case of Hypersensitivity to Mosquito Bite Associated with Epstein-Barr Viral Infection and Natural Killer Cell Lymphocytosis

    PubMed Central

    Roh, Eui Jung; Chang, Young Pyo; Myoung, Na Hye; Jee, Young Koo; Seo, Min; Kang, Jin Han

    2010-01-01

    Hypersensitivity to mosquito bites (HMB) is a disorder characterized by a necrotic skin reaction and generalized symptoms subsequent to mosquito bites. It has been suggested that HMB is associated with chronic Epstein-Barr virus (EBV) infection and natural killer cell leukemia/lymphoma. We describe here a Korean child who had HMB associated with chronic EBV infection and natural killer cell lymphocytosis. A 5-yr-old boy was suffered from necrotic skin lesions on the right ear lobe. Type A EB virus was detected from hlood cells and bone marrow biospy recognized hemophagocyrosis. PMID:20119592

  9. A case of hypersensitivity to mosquito bite associated with Epstein-barr viral infection and natural killer cell lymphocytosis.

    PubMed

    Roh, Eui Jung; Chung, Eun Hee; Chang, Young Pyo; Myoung, Na Hye; Jee, Young Koo; Seo, Min; Kang, Jin Han

    2010-02-01

    Hypersensitivity to mosquito bites (HMB) is a disorder characterized by a necrotic skin reaction and generalized symptoms subsequent to mosquito bites. It has been suggested that HMB is associated with chronic Epstein-Barr virus (EBV) infection and natural killer cell leukemia/lymphoma. We describe here a Korean child who had HMB associated with chronic EBV infection and natural killer cell lymphocytosis. A 5-yr-old boy was suffered from necrotic skin lesions on the right ear lobe. Type A EB virus was detected from hlood cells and bone marrow biospy recognized hemophagocyrosis.

  10. Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients.

    PubMed

    Kuhls, Deborah A; Rathmacher, John A; Musngi, M Diana; Frisch, Donald A; Nielson, Jeremiah; Barber, Annabel; MacIntyre, Allan D; Coates, Jay E; Fildes, John J

    2007-01-01

    Negative nitrogen balance and skeletal muscle loss are common in critically injured patients and may contribute to morbidity, mortality and resource utilization. Juven, an enteral supplement which is a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine (ARG), and glutamine (GLN) has been shown to restore muscle in cachetic acquired immunodeficiency syndrome (AIDS) and cancer patients. More recently HMB has been shown to attenuate cancer-induced muscle loss by decreasing muscle proteolysis. The purpose of this study was to analyze whether HMB alone or in combination with ARG and GLN would have a similar effect on critically injured trauma patients. We hypothesized that nitrogen balance would be improved and muscle proteolysis decreased with HMB and HMB/ARG/GLN supplementation. There were 100 adult trauma patients with Injury Severity Score (ISS) >18 were enrolled in this prospective, randomized, blinded study. All patients received standard tube feeds and one of three iso-nitrogenous supplements; HMB, HMB/ARG/ GLN, or placebo (PLAC) for 28 days. Urine, serum, and clinical data were collected for 72 patients receiving at least 7 days of supplementation during the first 14 days of treatment. Urinary 3-methylhistidine (3-MH) was used as a proxy for muscle proteolysis. The three groups were similar in age, gender, mechanism, and severity of injury, with the average ISS being 31.9. Utilizing covariant (ISS) repeated measure (days 1-14) mixed model (SAS) analysis, there was a significant treatment effect (p = 0.05) on nitrogen balance (g/d). Change in nitrogen balance from the first 7 days to the last 7 days was -4.3 for the HMB and -5.6 g/d HMB/ARG/GLN groups compared with -8.9 g/d for the PLAC group. 3-MH to creatinine ratios were not different in the PLAC group as compared with the HMB/ARG/GLN and HMB groups (Treatment Effect, p = 0.80). These data suggest that supplementation with HMB alone may improve nitrogen balance in critically injured adult patients

  11. Levonorgestrel intrauterine system: Current role in management of heavy menstrual bleeding

    PubMed Central

    Magon, Navneet; Chauhan, Monica; Goel, Poonam; Malik, Sonia; Kapur, Krishan; Kriplani, Alka; Dhaliwal, Lakhbir; Pandit, Suchitra N.

    2013-01-01

    A review of literature was conducted to report on the effectiveness of levonorgestrel intrauterine system (LNG-IUS) in women with heavy menstrual bleeding (HMB). The relevant data were obtained by computerized searches of PubMed up to December 2012 and other references available with the authors. Information was obtained from references listed. Studies and case reports were excluded if they did not specifically provide information about LNG-IUS usage in women with HMB. After perusal, each relevant publication was summarized and appraised in terms of whether it contained information relevant to the stated objective. Available data shows that LNG-IUS therapy is effective and safe, providing significant reduction of menstrual bleeding in patients with HMB. LNG-IUS is a good strategy to reduce the number of hysterectomies in women with HMB. PMID:23833527

  12. Utilization of supplemental methionine sources by primary cultures of chick hepatocytes

    SciTech Connect

    Dibner, J.J.

    1983-10-01

    Utilization of 2-hydroxy-4-(methylthio) butanoic acid (HMB) as a substrate for protein synthesis was studied by using primary cultures of chick liver cells. Cultures were prepared by enzymatic dissociation of livers from week old Hubbard broiler chicks and were maintained for 4 days under nonproliferative conditions. Hepatocyte differentiation was verified by using dexamethasone induction of tyrosine aminotransferase activity. Conversion of (14C)HMB to L-methionine was shown by chromatographic analysis of hepatocyte protein hydrolysate and incorporation into protein was proven by cycloheximide inhibition of synthesis. When incorporation of HMB was compared to that of DL-methionine (DLM) equimolar quantities of the two sources were found in liver cell protein. These results support, at a cellular level, the conclusion that HMB and DLM are biochemically equivalent sources of methionine for protein synthesis.

  13. Studies on the oxidation of hexamethylbenzene 2: Preparation of dimethylpyromellitic acid

    NASA Technical Reports Server (NTRS)

    Chiba, K.; Tomura, S.

    1986-01-01

    Hexamethylbenzene (HMB) was difficult to be oxidized with an alkaline potassium permanganate solution, since HMB was insoluble in an aqueous alkaline solution. But, when HMB was warmed with 50% nitric acid for a short time, and then treated with aqueous potassium permanganate, the reaction occurred readily and dimethylpyromellitic acid was obtained. When HMB was warmed with 50% nitric acid for 1 to 2 minutes, a yellow material was produced, which was soluble in hot aqueous potassium hydroxide, though free from carboxylic acids. It contained a little amount of bis-(nitromethyl)prehnitene and several unknown compounds. Further, the heat stability of polyimide prepared by the reaction of tetramethyldimethylpyromellitate with 4,4 prime-diaminodiphenylmethane turned out to be nearly equal to that of polyimide prepared from tetramethylpyromellitate.

  14. Evaluation and Management of Adolescents with Abnormal Uterine Bleeding.

    PubMed

    Mullins, Tanya L Kowalczyk; Miller, Rachel J; Mullins, Eric S

    2015-09-01

    The International Federation of Gynecology and Obstetrics and the American Congress of Obstetricians and Gynecologists support the use of new terminology for abnormal uterine bleeding (AUB) to consistently categorize AUB by etiology. The term AUB can be further classified as AUB/heavy menstrual bleeding (HMB) (replacing the term "menorrhagia") or AUB/intermenstrual bleeding (replacing the term "metrorrhagia"). Although many cases of AUB in adolescent women are attributable to immaturity of the hypothalamic-pituitary-ovarian axis, underlying bleeding disorders should be considered in women with AUB/HMB. This article reviews the new terminology for AUB, discusses important relevant features of history and examination, presents the laboratory evaluation of HMB, and describes hormonal (oral contraceptive pills, progestin-only methods, long-acting reversible contraceptives including intrauterine systems), hematologic (tranexamic acid and desmopressin), and surgical management options for AUB/HMB.

  15. β-Hydroxy-β-methylbutyrate attenuates cytokine response during sustained military training.

    PubMed

    Hoffman, Jay R; Gepner, Yiftach; Stout, Jeffrey R; Hoffman, Mattan W; Ben-Dov, Daniel; Funk, Shany; Daimont, Ido; Jajtner, Adam R; Townsend, Jeremy R; Church, David D; Shelef, Ilan; Rosen, Philip; Avital, Guy; Chen, Yacov; Frankel, Hagai; Ostfeld, Ishay

    2016-06-01

    This study tested the hypothesis that of 23 days of β-hydroxy-β-methylbutyrate (HMB) supplementation can maintain muscle mass and attenuate the immune and inflammatory response in combat soldiers during highly intense military training. Soldiers were randomly assigned to either a HMB (n = 6) or placebo (PL; n = 7) group and provided with 3 g · day(-1) of either HMB or PL. During the final week of supplementation soldiers participated in extreme physical training, which included night navigation of 6-8 hours across difficult terrain carrying heavy loads combined with sleep deprivation (3.8 ± 3.0 h per night). Blood draws were performed prior to and following the supplementation period. Magnetic resonance imaging, which included diffusion tensor imaging sequence, was used for muscle fiber tracking analysis. Data was analyzed using a two-way mixed factorial analysis of variance. Magnitude-based inferences were used to provide inferences on the true effects that HMB may have had on the dependent variables compared to PL, calculated from 90% confidence intervals. Changes in tumor necrosis factor-α for HMB (-3.9 ± 8.2 pg · mL(-1)) were significantly lower (P = .043) compared to the change in PL (+4.0 ± 3.7 pg · mL(-1)). HMB ingestion was also very likely (92%-95% Likelihood) to lower granulocyte colony-stimulating factor and interleukin 10 compared to PL. In addition, HMB supplementation was likely (78%-87% likelihood) to reduce interferon-γ, interleukin 8, CX3CL1, and increase muscle volume for the adductor magnus (77% likelihood) compared to PL. In summary, the results of this study provides evidence that HMB supplementation may attenuate the inflammatory response to high intense military training, and maintain muscle quality. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. β-Hydroxy β-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.

    PubMed

    Noh, Kyung Kyun; Chung, Ki Wung; Choi, Yeon Ja; Park, Min Hi; Jang, Eun Ji; Park, Chan Hum; Yoon, Changshin; Kim, Nam Deuk; Kim, Mi Kyung; Chung, Hae Young

    2014-01-01

    Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β-hydroxy β-methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy.

  17. Seismic stratigraphy of the Heuksan mud belt in the southeastern Yellow Sea, Korea

    NASA Astrophysics Data System (ADS)

    Lee, Gwang-Soo; Yoo, Dong Geun; Bae, Sung Ho; Min, Gun-Hong; Kim, Seong-Pil; Choi, Hunsoo

    2015-12-01

    To establish the seismic stratigraphy of the Heuksan mud belt (HMB) and reconstruct its depositional history, approximately 1,600 km of high-resolution seismic data were newly obtained using chirp acoustic sub-bottom profiler, sparker, and air-gun seismic systems. Based on seismic stratigraphic analysis, the HMB can be divided into three major seismic units (I, II, and III, from top to bottom) and four subunits (II-a, II-b, III-a, and III-b) overlying transgressive sands, pre-last glacial maximum (LGM) deposits, and the acoustic basement. Each unit and subunit show different seismic facies and geometry, being clearly separated from each other by bounding surfaces formed since the LGM. The spatial distribution, thicknesses and volumes of the seismic units were determined and plotted to document the sequential formation of the HMB. The correlation between deep drill core data (HMB-101, HMB-102, HMB-103, YSDP-101, and YSDP-102) and the seismic data suggests that subunits III-b and III-a were formed by the continuous accumulation of fine-grained sediment with partial sandy sediment in an estuarine/deltaic environment during the early to middle transgressive stage, accompanied by landward migration of the shoreline. Subunits II-b and II-a were probably formed by re-deposition of large volumes of sediment eroded from unit III during the middle transgressive to early highstand stage. Unit I is interpreted as the most recent mud deposit representing the highstand systems tract when sea-level rise terminated. The careful definition of seismic units and their interpretation proposed in this study, on the basis of the large and partly new seismic dataset covering the entire HMB together with deep drill core data, have been instrumental in reconstructing the depositional environment and formation mechanisms of the HMB.

  18. Structural dynamics of a noncovalent charge transfer complex from femtosecond stimulated Raman spectroscopy.

    PubMed

    Fujisawa, Tomotsumi; Creelman, Mark; Mathies, Richard A

    2012-09-06

    Femtosecond stimulated Raman spectroscopy is used to examine the structural dynamics of photoinduced charge transfer within a noncovalent electron acceptor/donor complex of pyromellitic dianhydride (PMDA, electron acceptor) and hexamethylbenzene (HMB, electron donor) in ethylacetate and acetonitrile. The evolution of the vibrational spectrum reveals the ultrafast structural changes that occur during the charge separation (Franck-Condon excited state complex → contact ion pair) and the subsequent charge recombination (contact ion pair → ground state complex). The Franck-Condon excited state is shown to have significant charge-separated character because its vibrational spectrum is similar to that of the ion pair. The charge separation rate (2.5 ps in ethylacetate and ∼0.5 ps in acetonitrile) is comparable to solvation dynamics and is unaffected by the perdeuteration of HMB, supporting the dominant role of solvent rearrangement in charge separation. On the other hand, the charge recombination slows by a factor of ∼1.4 when using perdeuterated HMB, indicating that methyl hydrogen motions of HMB mediate the charge recombination process. Resonance Raman enhancement of the HMB vibrations in the complex reveals that the ring stretches of HMB, and especially the C-CH(3) deformations are the primary acceptor modes promoting charge recombination.

  19. The Prevalence and Impact of Heavy Menstrual Bleeding (Menorrhagia) in Elite and Non-Elite Athletes

    PubMed Central

    Bruinvels, Georgie; Burden, Richard; Brown, Nicola; Richards, Toby; Pedlar, Charles

    2016-01-01

    To identify the prevalence and impact of heavy menstrual bleeding (HMB) in exercising females where anemia may have a significant effect on training and performance a ‘Female Health Questionnaire’ was designed incorporating a validated diagnostic HMB series, demographics, exercise ability data, training status, anemia, iron supplementation and whether the menstrual cycle had affected training and performance. The survey was conducted in two stages; initially online, advertised via social media, and then repeated via face-to-face interviews with runners registered for the 2015 London Marathon. 789 participants responded to the online survey, and 1073 completed the survey at the marathon. HMB was reported by half of those online (54%), and by more than a third of the marathon runners (36%). Surprisingly, HMB was also prevalent amongst elite athletes (37%). Overall, 32% of exercising females reported a history of anemia, and 50% had previously supplemented with iron. Only a minority (22%) had sought medical advice. HMB is highly prevalent in exercising females, associated with self-reported anemia, increased use of iron supplementation and a perceived negative impact on performance. Further research is needed to investigate the impact of HMB, iron deficiency and anemia in exercising females. PMID:26901873

  20. Increased plasma clot permeability and susceptibility to lysis are associated with heavy menstrual bleeding of unknown cause: a case-control study.

    PubMed

    Szczepaniak, Piotr; Zabczyk, Michał; Undas, Anetta

    2015-01-01

    Formation of compact and poorly lysable clots has been reported in thromboembolic disorders. Little is known about clot properties in bleeding disorders. We hypothesized that more permeable and lysis-sensitive fibrin clots can be detected in women with heavy menstrual bleeding (HMB). We studied 52 women with HMB of unknown cause and 52 age-matched control women. Plasma clot permeability (Ks), turbidity and efficiency of fibrinolysis, together with coagulation factors, fibrinolysis proteins, and platelet aggregation were measured. Women with HMB formed looser plasma fibrin clots (+16% [95%CI 7-18%] Ks) that displayed lower maximum absorbancy (-7% [95%CI -9 - -1%] ΔAbsmax), and shorter clot lysis time (-17% [95%CI -23 - -11%] CLT). The HMB patients and controls did not differ with regard to coagulation factors, fibrinogen, von Willebrand antigen, thrombin generation markers and the proportion of subjects with defective platelet aggregation. The patients had lower platelet count (-12% [95%CI -19 - -2%]), tissue plasminogen activator antigen (-39% [95%CI -41 - -29%] tPA:Ag), and plasminogen activator inhibitor-1 antigen (-28% [95%CI -38 - -18%] PAI-1:Ag) compared with the controls. Multiple regression analysis upon adjustment for age, body mass index, glucose, and fibrinogen showed that decreased tPA:Ag and shortened CLT were the independent predictors of HMB. Increased clot permeability and susceptibility to fibrinolysis are associated with HMB, suggesting that altered plasma fibrin clot properties might contribute to bleeding disorders of unknown origin.

  1. Increased Plasma Clot Permeability and Susceptibility to Lysis Are Associated with Heavy Menstrual Bleeding of Unknown Cause: A Case-Control Study

    PubMed Central

    Szczepaniak, Piotr; Zabczyk, Michał; Undas, Anetta

    2015-01-01

    Background Formation of compact and poorly lysable clots has been reported in thromboembolic disorders. Little is known about clot properties in bleeding disorders. Objectives We hypothesized that more permeable and lysis-sensitive fibrin clots can be detected in women with heavy menstrual bleeding (HMB). Methods We studied 52 women with HMB of unknown cause and 52 age-matched control women. Plasma clot permeability (Ks), turbidity and efficiency of fibrinolysis, together with coagulation factors, fibrinolysis proteins, and platelet aggregation were measured. Results Women with HMB formed looser plasma fibrin clots (+16% [95%CI 7–18%] Ks) that displayed lower maximum absorbancy (-7% [95%CI -9 – -1%] ΔAbsmax), and shorter clot lysis time (-17% [95%CI -23 – -11%] CLT). The HMB patients and controls did not differ with regard to coagulation factors, fibrinogen, von Willebrand antigen, thrombin generation markers and the proportion of subjects with defective platelet aggregation. The patients had lower platelet count (-12% [95%CI -19 – -2%]), tissue plasminogen activator antigen (-39% [95%CI -41 – -29%] tPA:Ag), and plasminogen activator inhibitor-1 antigen (-28% [95%CI -38 – -18%] PAI-1:Ag) compared with the controls. Multiple regression analysis upon adjustment for age, body mass index, glucose, and fibrinogen showed that decreased tPA:Ag and shortened CLT were the independent predictors of HMB. Conclusions Increased clot permeability and susceptibility to fibrinolysis are associated with HMB, suggesting that altered plasma fibrin clot properties might contribute to bleeding disorders of unknown origin. PMID:25909989

  2. Optimization of a Hybrid Magnetic Bearing for a Magnetically Levitated Blood Pump via 3-D FEA

    PubMed Central

    Cheng, Shanbao; Olles, Mark W.; Burger, Aaron F.; Day, Steven W.

    2011-01-01

    In order to improve the performance of a magnetically levitated (maglev) axial flow blood pump, three-dimensional (3-D) finite element analysis (FEA) was used to optimize the design of a hybrid magnetic bearing (HMB). Radial, axial, and current stiffness of multiple design variations of the HMB were calculated using a 3-D FEA package and verified by experimental results. As compared with the original design, the optimized HMB had twice the axial stiffness with the resulting increase of negative radial stiffness partially compensated for by increased current stiffness. Accordingly, the performance of the maglev axial flow blood pump with the optimized HMBs was improved: the maximum pump speed was increased from 6000 rpm to 9000 rpm (50%). The radial, axial and current stiffness of the HMB was found to be linear at nominal operational position from both 3-D FEA and empirical measurements. Stiffness values determined by FEA and empirical measurements agreed well with one another. The magnetic flux density distribution and flux loop of the HMB were also visualized via 3-D FEA which confirms the designers’ initial assumption about the function of this HMB. PMID:22065892

  3. Optimization of a Hybrid Magnetic Bearing for a Magnetically Levitated Blood Pump via 3-D FEA.

    PubMed

    Cheng, Shanbao; Olles, Mark W; Burger, Aaron F; Day, Steven W

    2011-10-01

    In order to improve the performance of a magnetically levitated (maglev) axial flow blood pump, three-dimensional (3-D) finite element analysis (FEA) was used to optimize the design of a hybrid magnetic bearing (HMB). Radial, axial, and current stiffness of multiple design variations of the HMB were calculated using a 3-D FEA package and verified by experimental results. As compared with the original design, the optimized HMB had twice the axial stiffness with the resulting increase of negative radial stiffness partially compensated for by increased current stiffness. Accordingly, the performance of the maglev axial flow blood pump with the optimized HMBs was improved: the maximum pump speed was increased from 6000 rpm to 9000 rpm (50%). The radial, axial and current stiffness of the HMB was found to be linear at nominal operational position from both 3-D FEA and empirical measurements. Stiffness values determined by FEA and empirical measurements agreed well with one another. The magnetic flux density distribution and flux loop of the HMB were also visualized via 3-D FEA which confirms the designers' initial assumption about the function of this HMB.

  4. Heavy menstrual bleeding and health-associated quality of life in women with von Willebrand's disease

    PubMed Central

    GOVOROV, IGOR; EKELUND, LENA; CHAIRETI, ROZA; ELFVINGE, PETRA; HOLMSTRÖM, MARGARETA; BREMME, KATARINA; MINTS, MIRIAM

    2016-01-01

    Women with the inherited bleeding disorder von Willebrand's disease (VWD) face gender-specific hemostatic challenges during menstruation. Heavy menstrual bleeding (HMB) can negatively affect their overall life activities and the health-associated quality of life. The purpose of the present study was to investigate whether women with VWD experienced HMB and an impaired health-associated quality of life. The study subjects were recruited from the Coagulation Unit of Karolinska University Hospital. Information was retrieved from various self-administered forms and medical records. Of the 30 women (18–52 years) that were included in the present study, 50% suffered from HMB, although the majority received treatment for HMB. In addition, almost all the included women perceived limitations in the overall life activities due to menstruation. The health-associated quality of life for women with HMB was significantly lower (P<0.10) with regards to ‘bodily pain’ compared with Swedish women of the general population. In conclusion, women with VWD experienced reduced health-associated quality of life as a result of HMB. Therefore, preventing limitations in overall life activities and improving their health-associated quality of life thorough counseling on menstrual bleeding is important for women with VWD. PMID:27168829

  5. Heavy menstrual bleeding: work-up and management.

    PubMed

    James, Andra H

    2016-12-02

    Heavy menstrual bleeding (HMB), which is the preferred term for menorrhagia, affects ∼90% of women with an underlying bleeding disorder and ∼70% of women on anticoagulation. HMB can be predicted on the basis of clots of ≥1 inch diameter, low ferritin, and "flooding" (a change of pad or tampon more frequently than hourly). The goal of the work-up is to determine whether there is a uterine/endometrial cause, a disorder of ovulation, or a disorder of coagulation. HMB manifest by flooding and/or prolonged menses, or HMB accompanied by a personal or family history of bleeding is very suggestive of a bleeding disorder and should prompt a referral to a hematologist. The evaluation will include the patient's history, pelvic examination, and/or pelvic imaging, and a laboratory assessment for anemia, ovulatory dysfunction, underlying bleeding disorder, and in the case of the patient on anticoagulation, assessment for over anticoagulation. The goal of treatment is to reduce HMB. Not only will the treatment strategy depend on whether there is ovulatory dysfunction, uterine pathology, or an abnormality of coagulation, the treatment strategy will also depend on the age of the patient and her desire for immediate or long-term fertility. Hemostatic therapy for HMB may serve as an alternative to hormonal or surgical therapy, and may even be life-saving when used to correct an abnormality of coagulation. © 2016 by The American Society of Hematology. All rights reserved.

  6. The Prevalence and Impact of Heavy Menstrual Bleeding (Menorrhagia) in Elite and Non-Elite Athletes.

    PubMed

    Bruinvels, Georgie; Burden, Richard; Brown, Nicola; Richards, Toby; Pedlar, Charles

    2016-01-01

    To identify the prevalence and impact of heavy menstrual bleeding (HMB) in exercising females where anemia may have a significant effect on training and performance a 'Female Health Questionnaire' was designed incorporating a validated diagnostic HMB series, demographics, exercise ability data, training status, anemia, iron supplementation and whether the menstrual cycle had affected training and performance. The survey was conducted in two stages; initially online, advertised via social media, and then repeated via face-to-face interviews with runners registered for the 2015 London Marathon. 789 participants responded to the online survey, and 1073 completed the survey at the marathon. HMB was reported by half of those online (54%), and by more than a third of the marathon runners (36%). Surprisingly, HMB was also prevalent amongst elite athletes (37%). Overall, 32% of exercising females reported a history of anemia, and 50% had previously supplemented with iron. Only a minority (22%) had sought medical advice. HMB is highly prevalent in exercising females, associated with self-reported anemia, increased use of iron supplementation and a perceived negative impact on performance. Further research is needed to investigate the impact of HMB, iron deficiency and anemia in exercising females.

  7. Iron deficiency and fatigue in adolescent females with heavy menstrual bleeding.

    PubMed

    Wang, W; Bourgeois, T; Klima, J; Berlan, E D; Fischer, A N; O'Brien, S H

    2013-03-01

    Iron deficiency and fatigue are common problems in adolescent females. Heavy menstrual bleeding (HMB) is associated with both iron deficiency and fatigue. The aim of this study was to define baseline ferritin values and fatigue symptoms in a population of young females with excessive menstrual blood loss, as compared to healthy controls. The study population included 11 to 17-year-old menstruating females presenting to an Adolescent Gynaecology Clinic, Menorrhagia Clinic or Sports Medicine clinic. To evaluate the degree and effects of menstrual blood loss, we utilized the Ruta Menorrhagia Severity Score. We investigated the symptoms of fatigue using the Fatigue Severity Scale. We evaluated possible predictors of ferritin level (age, body mass index, fatigue scores and Menorrhagia Severity Score) using generalized linear models. A total of 48 adolescents with HMB and 102 healthy adolescents completed the study. Iron deficiency and elevated fatigue scores were common findings in young women with HMB. Both fatigue severity scores and menorrhagia severity scores were significantly higher in young women with HMB as compared to healthy controls. In adolescents with HMB, 87.5% had ferritin levels ≤40 ng mL(-1), and 29.2% had ferritin levels ≤15 ng mL(-1). Our generalized linear models did not identify any significant univariate relationships between ferritin levels and patient age, body mass index, fatigue score or menorrhagia score. Iron deficiency and symptoms of fatigue are common findings in young women with HMB. Fatigue severity scores are significantly higher in young women with HMB as compared to healthy controls. © 2012 Blackwell Publishing Ltd.

  8. Dietary supplementation with β-hydroxy-β-methylbutyrate calcium during the early postnatal period accelerates skeletal muscle fibre growth and maturity in intra-uterine growth-retarded and normal-birth-weight piglets.

    PubMed

    Wan, Haifeng; Zhu, Jiatao; Su, Guoqi; Liu, Yan; Hua, Lun; Hu, Liang; Wu, Caimei; Zhang, Ruinan; Zhou, Pan; Shen, Yong; Lin, Yan; Xu, Shengyu; Fang, Zhengfeng; Che, Lianqiang; Feng, Bin; Wu, De

    2016-04-01

    Intra-uterine growth restriction (IUGR) impairs postnatal growth and skeletal muscle development in neonatal infants. This study evaluated whether dietary β-hydroxy-β-methylbutyrate Ca (HMB-Ca) supplementation during the early postnatal period could improve muscle growth in IUGR neonates using piglets as a model. A total of twelve pairs of IUGR and normal-birth-weight (NBW) male piglets with average initial weights (1·85 (sem 0·36) and 2·51 (sem 0·39) kg, respectively) were randomly allotted to groups that received milk-based diets (CON) or milk-based diets supplemented with 800 mg/kg HMB-Ca (HMB) during days 7-28 after birth. Blood and longissimus dorsi (LD) samples were collected and analysed for plasma amino acid content, fibre morphology and the expression of genes related to muscle development. The results indicate that, regardless of diet, IUGR piglets had a significantly decreased average daily weight gain (ADG) compared with that of NBW piglets (P<0·05). However, IUGR piglets fed HMB-Ca had a net weight and ADG similar to that of NBW piglets fed the CON diet. Irrespective of body weight (BW), HMB-Ca supplementation markedly increased the type II fibre cross-sectional area and the mRNA expression of mammalian target of rapamycin (mTOR), insulin-like growth factor-1 and myosin heavy-chain isoform IIb in the LD of piglets (P<0·05). Moreover, there was a significant interaction between the effects of BW and HMB on mTOR expression in the LD (P<0·05). In conclusion, HMB-Ca supplementation during the early postnatal period could improve skeletal muscle growth and maturity by accelerating fast-twitch glycolytic fibre development in piglets.

  9. Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

    PubMed Central

    Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

    2015-01-01

    BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

  10. β-hydroxy-β-methylbutyrate did not enhance high intensity resistance training-induced improvements in myofiber dimensions and myogenic capacity in aged female rats.

    PubMed

    Kim, Jeong-Su; Park, Young-Min; Lee, Sang-Rok; Masad, Ihssan S; Khamoui, Andy V; Jo, Edward; Park, Bong-Sup; Arjmandi, Bahram H; Panton, Lynn B; Lee, Won Jun; Grant, Samuel C

    2012-11-01

    Older women exhibit blunted skeletal muscle hypertrophy following resistance training (RT) compared to other age and gender cohorts that is partially due to an impaired regenerative capacity. In the present study, we examined whether β-hydroxy-β-methylbutyrate (HMB) provision to aged female rodents would enhance regenerative mechanisms and facilitate RT-induced myofiber growth. Nineteen-month old female Sprague-Dawley rats were randomly divided into three groups: HMB (0.48 g/kg/d; n = 6), non-HMB (n = 6), and control (n = 4). HMB and non-HMB groups underwent RT every third day for 10 weeks using a ladder climbing apparatus. Whole body strength, grip strength, and body composition was evaluated before and after RT. The gastrocnemius and soleus muscles were analyzed using magnetic resonance diffusion tensor imaging, RT-PCR, and immunohistochemistry to determine myofiber dimensions, transcript expression, and satellite cells/myonuclei, respectively. ANOVAs were used with significance set at p < 0.05. There were significant time effects (pre vs. post) for whole body strength (+262%), grip strength (+17%), lean mass (+20%), and fat mass (-19%). Both RT groups exhibited significant increases in the mean myofiber cross-sectional area (CSA) in the gastrocnemius and soleus (+8-22%) compared to control. Moreover, both groups demonstrated significant increases in the numbers of satellite cells (+100-108%) and myonuclei (+32%) in the soleus but not the gastrocnemius. A significant IGF-I mRNA elevation was only observed in soleus of the HMB group (+33%) whereas MGF and myogenin increased significantly in both groups (+32-40%). Our findings suggest that HMB did not further enhance intense RT-mediated myogenic mechanisms and myofiber CSA in aged female rats.

  11. Effect of excess methionine and methionine hydroxy analogue on growth performance and plasma homocysteine of growing Pekin ducks.

    PubMed

    Xie, M; Hou, S S; Huang, W; Fan, H P

    2007-09-01

    One experiment was conducted to study the effect of excess dl-methionine (DLM) and dl-2-hydroxy-4-methylthiobutanoic acid free acid (dl-HMB-FA) on duck growth. One-day-old male white Pekin ducklings were fed common starter diets from hatch to 21 d of age and then fed the experimental diets from 21 to 42 d of age. Three hundred twenty 21-d-old birds were allotted to 40 raised wire-floor pens with 8 birds per pen according to similar pen weight. There were 5 dietary treatments that included a methionine-adequate control diet and control diets supplemented with 2 levels of dry DLM (1 or 2%) or 2 equimolar levels of liquid dl-HMB-FA (1.13 or 2.26%). Each dietary treatment was replicated 8 times. At 42 d of age, weight gain, feed intake, and gain/feed were measured and plasma was collected to analyze homocysteine. Compared with ducks fed control diets, excess DLM or dl-HMB-FA supplementation reduced weight gain and feed intake of birds significantly. However, on the equimolar basis, at 1 or 2% supplemental methionine activity, dl-HMB-FA was less growth-depressing than DLM. According to the growth response to excess methionine, the tolerable upper limit of dietary methionine for growing ducks may be less than 1.38% when the methionine level of the control diet (0.38%) was considered. On the other hand, plasma homocysteine was elevated markedly when 2% DLM or 2.26% dl-HMB-FA was added to control diets, but plasma homocysteine of ducks fed 2.26% dl-HMB-FA supplemented diets was lower significantly than birds fed equimolar DLM-supplemented diets, which indicated the toxicity of excess methionine sources and less toxicity of dl-HMB-FA relative to DLM.

  12. Formation of isobutene from 3-hydroxy-3-methylbutyrate by diphosphomevalonate decarboxylase.

    PubMed

    Gogerty, David S; Bobik, Thomas A

    2010-12-01

    Isobutene is an important commercial chemical used for the synthesis of butyl rubber, terephthalic acid, specialty chemicals, and a gasoline performance additive known as alkylate. Currently, isobutene is produced from petroleum and hence is nonrenewable. Here, we report that the Saccharomyces cerevisiae mevalonate diphosphate decarboxylase (ScMDD) can convert 3-hydroxy-3-methylbutyrate (3-HMB) to isobutene. Whole cells of Escherichia coli producing ScMDD with an N-terminal 6×His tag (His(6)-ScMDD) formed isobutene from 3-HMB at a rate of 154 pmol h(-1) g cells(-1). In contrast, no isobutene was detected from control cells lacking ScMDD. His(6)-ScMDD was purified by nickel affinity chromatography and shown to produce isobutene from 3-HMB at a rate of 1.33 pmol min(-1) mg(-1) protein. Controls showed that both His(6)-ScMDD and 3-HMB were required for detectable isobutene formation. Isobutene was identified by gas chromatography (GC) with flame ionization detection as well as by GC-mass spectrometry (MS). ScMDD was subjected to error-prone PCR, and two improved variants were characterized, ScMDD1 (I145F) and ScMDD2 (R74H). Whole cells of E. coli producing ScMDD1 and ScMDD2 produced isobutene from 3-HMB at rates of 3,000 and 5,888 pmol h(-1) g cells(-1), which are 19- and 38-fold increases compared to rates for cells producing His(6)-ScMDD. This showed that genetic modifications can be used to increase the rate at which ScMDD converts 3-HMB to isobutene. Because 3-HMB can be produced from l-leucine, ScMDD has a potential application for the production of renewable isobutene. Moreover, isobutene is a gas, which might simplify its purification from a fermentation medium, substantially reducing production costs.

  13. Effects of β-hydroxy-β-methyl butyrate on working memory and cognitive flexibility in an animal model of aging.

    PubMed

    Hankosky, Emily R; Sherrill, Luke K; Ruvola, Lauren A; Haake, Rachel M; Kim, Taehyeon; Hammerslag, Lindsey R; Kougias, Daniel G; Juraska, Janice M; Gulley, Joshua M

    2017-09-01

    Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) on working memory and cognitive flexibility. Beginning ∼12 months of age, male and female Long-Evans rats were given twice daily access to sipper tubes containing calcium HMB (450 mg/kg) or vehicle (285 mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.

  14. Interaction of Beta-Hydroxy-Beta-Methylbutyrate Free Acid and Adenosine Triphosphate on Muscle Mass, Strength, and Power in Resistance Trained Individuals.

    PubMed

    Lowery, Ryan P; Joy, Jordan M; Rathmacher, John A; Baier, Shawn M; Fuller, John C; Shelley, Mack C; Jäger, Ralf; Purpura, Martin; Wilson, Stephanie M C; Wilson, Jacob M

    2016-07-01

    Lowery, RP, Joy, JM, Rathmacher, JA, Baier, SM, Fuller, JC Jr, Shelley, MC II, Jäger, R, Purpura, M, Wilson, SMC, and Wilson, JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30(7): 1843-1854, 2016-Adenosine-5'-triphosphate (ATP) supplementation helps maintain performance under high fatiguing contractions and with greater fatigue recovery demands also increase. Current evidence suggests that the free acid form of β-hydroxy-β-methylbutyrate (HMB-FA) acts by speeding regenerative capacity of skeletal muscle after high-intensity or prolonged exercise. Therefore, we investigated the effects of 12 weeks of HMB-FA (3 g) and ATP (400 mg) administration on lean body mass (LBM), strength, and power in trained individuals. A 3-phase double-blind, placebo-, and diet-controlled study was conducted. Phases consisted of an 8-week periodized resistance training program (phase 1), followed by a 2-week overreaching cycle (phase 2), and a 2-week taper (phase 3). Lean body mass was increased by a combination of HMB-FA/ATP by 12.7% (p < 0.001). In a similar fashion, strength gains after training were increased in HMB-FA/ATP-supplemented subjects by 23.5% (p < 0.001). Vertical jump and Wingate power were increased in the HMB-FA/ATP-supplemented group compared with the placebo-supplemented group, and the 12-week increases were 21.5 and 23.7%, respectively. During the overreaching cycle, strength and power declined in the placebo group (4.3-5.7%), whereas supplementation with HMB-FA/ATP resulted in continued strength gains (1.3%). In conclusion, HMB-FA and ATP in combination with resistance exercise training enhanced LBM, power, and strength. In addition, HMB-FA plus ATP blunted the typical response to overreaching, resulting in a further increase in strength during that period. It seems that the combination of HMB-FA/ATP could benefit those who

  15. The effect of increasing concentrations of dl-methionine and 2-hydroxy-4-(methylthio) butanoic acid on hepatic genes controlling methionine regeneration and gluconeogenesis.

    PubMed

    Zhang, Qian; Bertics, Sandra J; Luchini, N Daniel; White, Heather M

    2016-10-01

    Metabolizable methionine (Met) concentrations can be increased by feeding rumen-protected dl-Met or the isopropyl ester of 2-hydroxy-4-(methylthio) butanoic acid (HMBi). Hepatic responses to increasing concentrations of metabolizable Met as a result of supplementation of different Met sources have not been comparatively examined. The objective of this experiment was to examine the regulation of key genes for Met metabolism, gluconeogenesis, and fatty acid oxidation in response to increasing concentrations of dl-Met or 2-hydroxy-4-(methylthio) butanoic acid (HMB) in bovine primary hepatocytes. Hepatocytes isolated from 4 Holstein calves less than 7d old were maintained as monolayer cultures for 24h before addition of treatments. Cells were then exposed to treatments of dl-Met or HMB (0, 10, 20, 40, or 60 µM) in Met-free medium for 24h and collected for RNA isolation and quantification of gene expression by quantitative PCR. Expression of betaine-homocysteine methyltransferase (BHMT), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and 5,10 methylenetetrahydrofolate reductase (MTHFR) genes, which catalyze regeneration of Met from betaine and homocysteine, decreased linearly with increasing dl-Met concentration. We observed similar effects with increasing HMB concentration, except expression of MTHFR, which was not altered. Expression of Met adenosyltransferase 1A (MAT1A), which catalyzes the first step of Met metabolism to generate S-adenosylmethionine (SAM), a primary methyl donor, was decreased with increasing dl-Met or HMB concentration. Expression of S-adenosylhomocysteine hydrolase (SAHH) was decreased linearly with increasing HMB concentration, but not altered by dl-Met. Increasing concentrations of dl-Met and HMB decreased cytosolic phosphoenolpyruvate carboxykinase (PCK1) expression, but did not alter the expression of mitochondrial phosphoenolpyruvate carboxykinase (PCK2) or pyruvate carboxylase (PC). Expression of glucose-6-phosphatase(G6PC

  16. Structural Insights into E. coli Porphobilinogen Deaminase during Synthesis and Exit of 1-Hydroxymethylbilane

    PubMed Central

    Bulusu, Gopalakrishnan

    2014-01-01

    Porphobilinogen deaminase (PBGD) catalyzes the formation of 1-hydroxymethylbilane (HMB), a crucial intermediate in tetrapyrrole biosynthesis, through a step-wise polymerization of four molecules of porphobilinogen (PBG), using a unique dipyrromethane (DPM) cofactor. Structural and biochemical studies have suggested residues with catalytic importance, but their specific role in the mechanism and the dynamic behavior of the protein with respect to the growing pyrrole chain remains unknown. Molecular dynamics simulations of the protein through the different stages of pyrrole chain elongation suggested that the compactness of the overall protein decreases progressively with addition of each pyrrole ring. Essential dynamics showed that domains move apart while the cofactor turn region moves towards the second domain, thus creating space for the pyrrole rings added at each stage. Residues of the flexible active site loop play a significant role in its modulation. Steered molecular dynamics was performed to predict the exit mechanism of HMB from PBGD at the end of the catalytic cycle. Based on the force profile and minimal structural changes the proposed path for the exit of HMB is through the space between the domains flanking the active site loop. Residues reported as catalytically important, also play an important role in the exit of HMB. Further, upon removal of HMB, the structure of PBGD gradually relaxes to resemble its initial stage structure, indicating its readiness to resume a new catalytic cycle. PMID:24603363

  17. Intermediates in the Recycling of 5-Methylthioribose to Methionine in Fruits 1

    PubMed Central

    Kushad, Mosbah M.; Richardson, Daryl G.; Ferro, Adolph J.

    1983-01-01

    The recycling of 5-methylthioribose (MTR) to methionine in avocado (Persea americana Mill, cv Hass) and tomato (Lycopersicum esculentum Mill, cv unknown) was examined. [14CH3]MTR was not metabolized in cell free extract from avocado fruit. Either [14CH3]MTR plus ATP or [14CH3]5-methylthioribose-1-phosphate (MTR-1-P) alone, however, were metabolized to two new products by these extracts. MTR kinase activity has previously been detected in these fruit extracts. These data indicate that MTR must be converted to MTR-1-P by MTR kinase before further metabolism can occur. The products of MTR-1-P metabolism were tentatively identified as α-keto-γ-methylthiobutyric acid (α-KMB) and α-hydroxy-γ-methylthiobutyric acid (α-HMB) by chromatography in several solvent systems. [35S]α-KMB was found to be further metabolized to methionine and α-HMB by these extracts, whereas α-HMB was not. However, α-HMB inhibited the conversion of α-KMB to methionine. Both [U-14C]α-KMB and [U-14C]methionine, but not [U-14C]α-HMB, were converted to ethylene in tomato pericarp tissue. In addition, aminoethoxyvinylglycine inhibited the conversion of α-KMB to ethylene. These data suggest that the recycling pathway leading to ethylene is MTR → MTR-1-P → α-KMB → methionine → S-adenosylmethionine → 1-aminocyclopropane-1-carboxylic acid → ethylene. PMID:16663204

  18. Effect of ginger (Zingiber officinale) on heavy menstrual bleeding: a placebo-controlled, randomized clinical trial.

    PubMed

    Kashefi, Farzaneh; Khajehei, Marjan; Alavinia, Mohammad; Golmakani, Ebrahim; Asili, Javad

    2015-01-01

    A wide range of herbal plants have been reported to treat various gynecological problems of women. This study was set out to investigate the effect of ginger (Zingiber officinale) on heavy menstrual bleeding (HMB) in high school girls. Ninety-two young women who experienced HMB and met the inclusion criteria were recruited in this study. Participants were evaluated for six consecutive menstrual cycles. During 3 assessment cycles, their HMB was confirmed by Pictorial Blood Assessment Chart. They were then randomly allocated to two study groups to receive either ginger or placebo capsules. The participants filled in the same chart during three intervention cycles. The level of menstrual blood loss dramatically declined during the three intervention cycles in ginger-receiving group. The decrease of blood loss in ginger-receiving group was significantly more remarkable than that of participants receiving placebo (p<0.001). Minimum number of participants reported adverse effects. HMB is highly prevalent among young women. Considering the significance of appropriate and timely treatment and also the importance of prevention of unwanted consequences, ginger may be considered as an effective therapeutic option for HMB. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Exercise-induced muscle damage is not attenuated by beta-hydroxy-beta-methylbutyrate and alpha-ketoisocaproic acid supplementation.

    PubMed

    Nunan, David; Howatson, Glyn; van Someren, Ken A

    2010-02-01

    The purpose of this study was to examine the effects of combined oral beta-hydroxy-beta-methylbutyrate (HMB) and alpha-ketoisocaproic acid (KIC) supplementation on indices of exercise-induced muscle damage (EIMD) after an acute bout of eccentric-biased exercise. Fourteen male subjects were allocated to 2 groups: a placebo group (3 g.d corn flour, N = 7) or an HMB + KIC group (3 g.d HMB and 0.3 g.d KIC, N = 7). Supplementation commenced 11 days before a 40-minute bout of downhill running and continued for 3 days post-exercise. Delayed-onset muscle soreness, mid-thigh girth, knee extensor range of motion, serum creatine kinase (CK) activity, and isometric and concentric torque were assessed pre-exercise and at 24, 48, and 72 hours post-exercise. Delayed-onset muscle soreness, CK activity, and isometric and concentric torque all changed over the 72-hour period (p < 0.05); however, HMB + KIC had no significant effect on any of the indices of muscle damage. Although 14 days HMB and KIC supplementation did not attenuate indices of EIMD after an acute bout of unaccustomed eccentric-biased exercise, there was a trend for a more rapid rate of recovery in isometric and isokinetic muscle function. beta-hydroxy-beta-methylbutyrate and KIC may therefore provide limited benefit in the recovery of muscle function after EIMD in untrained subjects or after unaccustomed exercise.

  20. Menstrual questionnaires for clinical and research use.

    PubMed

    Matteson, Kristen A

    2017-04-01

    Patient-reported outcome measures (PROMs) have the potential to be extremely valuable in the clinical care delivery for women who report heavy menstrual bleeding (HMB). Increasingly, studies on HMB have incorporated PROMs to evaluate the impact of bleeding on quality of life. These measures have included semiquantitative charts and pictograms, questionnaires to assess symptoms and impact on quality of life, and health-related quality of life questionnaires. Recent systematic reviews have highlighted inconsistency of outcome measurement across studies on HMB as a challenge limiting the interpretability of the body of literature and the ability to generate consensus on the relative effectiveness of treatment options. Consequently, research initiatives and international collaborations are working to harmonize outcome measurement. Harmonizing the use of questionnaires in research and clinical care has the potential to improve patient-centered care delivery for women with HMB and improve the generation of patient-focused evidence-based guidelines for the evaluation and treatment of HMB. Copyright © 2016. Published by Elsevier Ltd.

  1. The knowns and unknowns of human milk banking.

    PubMed

    Simmer, Karen; Hartmann, Ben

    2009-11-01

    The PREM Bank has been providing pasteurised donor human milk (PDHM) to very preterm for the past 3 years. It is the first human milk bank (HMB) to operate in Australia in over 20 years. Our community has rapidly embraced the concept of human milk banking, with both donations and demand for PDHM exceeding expectations. Providing PDHM in 'exceptional circumstances' where a mothers' own milk is unavailable is supported by the WHO and UNICEF. We submit that neonatal intensive care is an exceptional circumstance. Although evidence supporting PDHM use from randomised control trial (RCT) is limited, the latest systematic reviews suggest a lower risk of necrotising enterocolitis with PDHM as opposed to artificial formula. Study design and ethical issues may limit future evidence from RCT. We therefore support the ongoing use of PDHM in neonatal care, where provided by an appropriately managed HMB. Internationally many HMBs operate unregulated, and this is also the case in Australia. To ensure safety the PREM Bank has committed to meet the appropriate standards recommended in the Code of Good Manufacturing Practices (Blood and Tissues) in Australia and models risk management during processing on Codex HACCP (Hazard Analysis Critical Control Point) requirements. There is scope to continually re-evaluate the screening of donors and quality standards recommended during HMB. This will be most effective if strong networks of HMBs are developed with regional reference laboratories to encourage compliance with safety guidelines. HMB networks will facilitate collection of evidence for refining HMB practice and improving outcomes for preterm and sick infants.

  2. Flywheel Energy Storage System Suspended by Hybrid Magnetic Bearing

    NASA Astrophysics Data System (ADS)

    Owusu-Ansah, Prince; Hu, Yefa; Misbawu, Adam

    This work presents a prototype flywheel energy storage system (FESS) suspended by hybrid magnetic bearing (HMB) rotating at a speed of 20000rpm with a maximum storage power capacity of 30W with a maximum tip speed of 300m/s. The design presented is an improvement of most existing FESS, as the design incorporates a unique feature in that the upper and the lower rotor and stator core are tapered which enhances larger thrust and much lower radial force to be exerted on the system. Without any adverse effect being experienced by the model. The work also focuses on the description of developing a prototype FESS suspended by HMB using solid works as a basis of developing in the nearer future a more improved FESS suspended by HMB capable of injecting the ever increasing high energy demand situation in the 21st century and beyond.

  3. Hypersensitivity to mosquito bites as the primary clinical manifestation of an Epstein-Barr virus infection.

    PubMed

    Chiu, Tsu-Man; Lin, Yueh-Min; Wang, Shing-Chuang; Tsai, Yi-Giien

    2016-08-01

    Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by intense local skin reactions with general symptoms, such as high fever and regional lymphadenopathy after mosquito bites. Epstein-Barr virus (EBV) chronic infection and NK cell lymphoproliferative disease have been reported first in diagnosed HMB patients. Here, we present the case of a 6-year-old girl with 2 months' history of bullae and necrotic skin lesions, accompanied by a high temperature, visual hallucinations, and liver dysfunction after mosquito bites. A histopathologic examination of the skin lesion showed vasculitis and EBV infection. We could not detect any findings of hematologic malignancies or NK cell proliferative disease in the patient. Clinicians should closely evaluate HMB patients for possible development of lymphoproliferative status or hematologic malignant disorders. Copyright © 2014. Published by Elsevier B.V.

  4. Effects of β-hydroxy-β-methylbutyrate free acid and cold water immersion on expression of CR3 and MIP-1β following resistance exercise.

    PubMed

    Gonzalez, Adam M; Fragala, Maren S; Jajtner, Adam R; Townsend, Jeremy R; Wells, Adam J; Beyer, Kyle S; Boone, Carleigh H; Pruna, Gabriel J; Mangine, Gerald T; Bohner, Jonathan D; Fukuda, David H; Stout, Jeffrey R; Hoffman, Jay R

    2014-04-01

    The inflammatory response to muscle-damaging exercise requires monocyte mobilization and adhesion. Complement receptor type 3 (CR3) and macrophage inflammatory protein (MIP)-1β enables monocyte recruitment, adhesion, and subsequent infiltration into damaged muscle tissue. The purpose of this study was to examine the effects of cold water immersion (CWI) and/or β-hydroxy-β-methylbutyrate free acid (HMB-FA) on CR3 expression and MIP-1β concentration after four sets of up to 10 repetitions of squat, dead lift, and split squat exercises at 70-80% 1-repetition maximum. Thirty-nine resistance-trained men (22.2 ± 2.5 yr) were randomly divided into four groups: 1) placebo (PL), 2) HMB-FA, 3) HMB-FA-CWI, and 4) PL-CWI. The HMB-FA groups ingested 3 g/day, and CWI groups were submersed into 10-12°C water for 10 min after exercise. Blood was sampled at baseline (PRE), immediately post- (IP), 30 min post- (30P), 24 h post- (24P), and 48 h post (48P)-exercise. Circulating MIP-1β was assayed and CR3 expression on CD14+ monocytes was measured by flow cytometry. Without treatment, CR3 expression significantly elevated at 30P compared with other time points (P = 0.030-0.047). HMB-FA significantly elevated the percentage of monocytes expressing CR3 between IP and 24P (P = 0.046) and between IP and 48P (P = 0.046). No time effect was observed for MIP-1β concentration. The recovery modalities showed to attenuate the rise in CR3 following exercise. Additionally, supplementation with HMB-FA significantly elevated the percentage of monocytes expressing CR3 during recovery. Although the time course that inflammatory responses are most beneficial remains to be determined, recovery modalities may alter immune cell mobilization and adhesion mechanisms during tissue recovery.

  5. Necessity of human milk banking in Japan: Questionnaire survey of neonatologists.

    PubMed

    Mizuno, Katsumi; Sakurai, Motoichiro; Itabashi, Kazuo

    2015-08-01

    If their own mother's milk (OMM) is not available, another mother's milk may be used for extremely low-birthweight (ELBW) infants. Human milk is a bodily fluid, however, therefore we have assumed that other mother's milk is currently seldom given to infants despite its superiority to formula. Although the World Health Organization and the American Academy of Pediatrics have recommended using donor human milk (DHM) from a human milk bank (HMB) in the case that OMM is not available, there is no HMB in Japan. To assess whether other mother's milk is used for ELBW infants and whether an HMB is necessary in Japan, we surveyed neonatal intensive care units (NICU) via questionnaire. The questionnaire was sent by email to members of the Japanese Neonatologist Association who are responsible for NICU. In total, 126 completed questionnaires (70.7%) were returned and analyzed. One-fourth of NICU give other mother's milk to ELBW infants. The first choice of nutrition is OMM, but other mother's milk or formula is given to infants at 19% of NICU if OMM is unavailable. Approximately three-fourths of NICU would like an HMB. Although human milk contains contagious agents and authorities do not recommend giving other mother's milk as a substitute for OMM, other mother's milk is still a choice in NICU in Japan. Many neonatologists, however, would prefer a safer alternative, that is, DHM obtained from an accredited HMB. A well-regulated HMB should be established and safe DHM should be available for all preterm infants if necessary. © 2015 Japan Pediatric Society.

  6. Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis.

    PubMed

    Wu, Hongmei; Xia, Yang; Jiang, Jin; Du, Huanmin; Guo, Xiaoyan; Liu, Xing; Li, Chunlei; Huang, Guowei; Niu, Kaijun

    2015-01-01

    Beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of the branched-chain amino acid leucine, has been investigated as a potential supplement to improve muscle quality; however, whether HMB supplementation has beneficial effects on muscle loss in older adults remains unclear. Systematic review with meta-analysis. PubMed, Medline and EMBASE databases were searched from the earliest possible year to September 2014. Individuals aged 65 years and older that reported absolute changes in body composition with use of HMB. Two review authors working independently reviewed the trials, and standard mean difference was calculated using a fixed effects model. A total of seven randomized controlled trials were included, in which 147 older adults received HMB intervention and 140 were assigned to control groups. The meta-analysis showed greater muscle mass gain in the intervention groups compared with the control groups (standard mean difference=0.352kg; 95% confidence interval: 0.11, 0.594; Z value=2.85; P=0.004). There were no significant fat mass changes between intervention and control groups (standard mean difference=-0.08kg; 95% confidence interval: -0.32, 0.159; Z value=0.66; P=0.511). Beta-hydroxy-beta-methylbutyrate supplementation contributed to preservation of muscle mass in older adults. HMB supplementation may be useful in the prevention of muscle atrophy induced by bed rest or other factors. Further studies are needed to determine the precise effects of HMB on muscle strength and physical function in older adults. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Presence of human milk bank is associated with elevated rate of exclusive breastfeeding in VLBW infants.

    PubMed

    Arslanoglu, Sertac; Moro, Guido E; Bellù, Roberto; Turoli, Daniela; De Nisi, Giuseppe; Tonetto, Paola; Bertino, Enrico

    2013-03-01

    Human milk confers health benefits of vital importance for the sick and preterm infants in neonatal intensive care units (NICUs). Mother's own milk is the first choice in preterm infant feeding, and every effort should be made to promote lactation. When mother's milk is not available or is insufficient, donor human milk (DHM) is recommended. Yet, occasionally, the concern that the use of DHM might decrease breastfeeding is being raised. The present data collection planned by the Italian Association of Human Milk Banks (AIBLUD) in collaboration with the Italian Neonatal Network (INN) attempted to address this concern. A total of 4277 very low birth weight (VLBW) infants from 83 Italian NICUs were evaluated for this comparative analysis. The 83 Italian NICUs were divided into two groups: centers with a human milk bank (HMB) and centers without a HMB; the available parameters in the network--"any and exclusive breastfeeding rates" and "exclusive formula rate" at discharge--were compared. Exclusive breastfeeding rate at discharge was significantly higher in NICUs with a HMB than in NICUs without (29.6% vs. 16.0%, respectively). Any breastfeeding rate at discharge tended to be higher in the NICUs with HMB (60.4% vs. 52.8%, P = 0.09), and exclusive formula rate was lower in the NICUs with HMB (26.5% vs. 31.3%), but this difference was not significant. This report shows that the presence of a HMB and the use of DHM in NICU are associated with increased breastfeeding rate at discharge from the hospital for VLBW infants.

  8. Resources and procedures in the treatment of heavy menstrual bleeding with the levonorgestrel-releasing intrauterine system (LNG-IUS) or hysterectomy in Brazil.

    PubMed

    Bahamondes, M Valeria; de Lima, Yuri; Teich, Vanessa; Bahamondes, Luis; Monteiro, Ilza

    2012-09-01

    Heavy menstrual bleeding (HMB) is the most common complaint of women seeking gynecological care. Treatments included surgical or medical options including hysterectomy and the levonorgestrel-releasing intrauterine system (LNG-IUS) due to the profound suppression of endometrial growth that intrauterine LNG exerts which results in amenorrhea or in a reduction of blood loss. The study was conducted to evaluate the resources and procedures involved in inserting an LNG-IUS compared to performing hysterectomy in women with HMB in a public sector hospital in Brazil. Two cohorts of women were studied: women who accepted an LNG-IUS (n=124) and matched women who underwent hysterectomy on the same day (n=122). We evaluate the number of procedures carried out in each group of women, including those performed before the decision was made to insert an LNG-IUS or to perform hysterectomy, the insertion of the device itself and the surgical procedure, in addition to the procedures and complications registered up to 1 year after LNG-IUS insertion or hysterectomy. Age and the duration of HMB were significantly lower in the LNG-IUS acceptors than women at the hysterectomy group. The numbers of gynecological consultations and Pap smears were similar in both groups; however, women in the hysterectomy group also underwent laboratory tests, ultrasonography, chest X-ray and electrocardiogram. In the hysterectomy group, the main complications were hemorrhage (six), bladder/bowel perforation (four), complications with anesthesia (one), ureteral reimplantation required (one) and abdominal pain (two). At 1 year, HMB was controlled in 83.1% of women in the LNG-IUS group, and 106 women continued with the device. Both treatments were effective in HMB control. Fewer resources and complications were observed in LNG-IUS acceptors when compared to hysterectomy. The LNG-IUS represents a good strategy for reducing the number of hysterectomies and the resources required for women with HMB. Copyright

  9. β-Hydroxy-β-methylbutyrate free acid reduces markers of exercise-induced muscle damage and improves recovery in resistance-trained men.

    PubMed

    Wilson, Jacob M; Lowery, Ryan P; Joy, Jordan M; Walters, Joe A; Baier, Shawn M; Fuller, John C; Stout, Jeffrey R; Norton, Layne E; Sikorski, Eric M; Wilson, Stephanie M C; Duncan, Nevine M; Zanchi, Nelo E; Rathmacher, John

    2013-08-28

    The purpose of the present study was to determine the effects of short-term supplementation with the free acid form of b-hydroxyb-methylbutyrate (HMB-FA) on indices of muscle damage, protein breakdown, recovery and hormone status following a high-volume resistance training session in trained athletes. A total of twenty resistance-trained males were recruited to participate in a high-volume resistance training session centred on full squats, bench presses and dead lifts. Subjects were randomly assigned to receive either 3 g/d of HMB-FA or a placebo. Immediately before the exercise session and 48 h post-exercise, serum creatine kinase (CK), urinary 3-methylhistadine (3-MH), testosterone, cortisol and perceived recovery status (PRS) scale measurements were taken. The results showed that CK increased to a greater extent in the placebo (329%) than in the HMB-FA group (104%) (P¼0·004, d ¼ 1·6). There was also a significant change for PRS, which decreased to a greater extent in the placebo (9·1 (SEM 0·4) to 4·6 (SEM 0·5)) than in the HMB-FA group (9·1 (SEM 0·3) to 6·3 (SEM 0·3)) (P¼0·005, d ¼ 20·48). Muscle protein breakdown, measured by 3-MH analysis, numerically decreased with HMB-FA supplementation and approached significance (P¼0·08, d ¼ 0·12). There were no acute changes in plasma total or free testosterone, cortisol or C-reactive protein. In conclusion, these results suggest that an HMB-FA supplement given to trained athletes before exercise can blunt increases in muscle damage and prevent declines in perceived readiness to train following a high-volume, muscle-damaging resistance-training session.

  10. Alkenone temperature of 84 core tops and Holocene sediments in the southeastern Yellow Sea

    NASA Astrophysics Data System (ADS)

    Bae, S. W.; Lee, K. E.; Chang, T. S.

    2016-12-01

    The C37 alkenones have been widely used for reconstruction of past sea surface temperatuer (SST) in open ocean, but there is an uncertainty about the applicability of alkenone paleothermometry at marginal sea, especially in the Yellow Sea. To test that, alkenone-based temperatures estimated using 84 surface sediments from the Heuksan Mud Belt (HMB), which is located in the southeastern Yellow Sea, were compared with horizontal, vertical, and seasonal distriubution pattern of in-situ temperature (data from NFRDI in Korea, 2005-2014). In addition, we reconstruct variations in Holocene high-resolution SST from the deep drilled core sediments (HMB-101 and HMB-103) recovered from the HMB. The values of core top alkenone temperatues and its spatial distribution pattern correspond well with those of in-situ temperature in spring to summer at depths of 0-10 m. Especially, the alkenone temperatures of southern part were relatively high compared to those of the northern part and they decreased northward, which is consistent to the general trend of in-situ temperature. These indicate that reconstructed alkenone temperature from the HMB marine sediments seems to represent the SST in spirng to summer. During the Holocene, the alkenone temperatures which were reconstructed from HMB cores ranged from 15.5 to 19 °C. The study area is characterized by high sedimentation rate of approximately 0.2 cm/yr and average temporal resolution of the reconstructed alkenone temperature record is 20 yr. Hence multi-centennial to millennial time scale SST variations during the Holocene will be able to be investigated based on the alkenone record.

  11. Mode of bindings of zinc oxide nanoparticles to myoglobin and horseradish peroxidase: A spectroscopic investigations

    NASA Astrophysics Data System (ADS)

    Mandal, Gopa; Bhattacharya, Sudeshna; Ganguly, Tapan

    2011-07-01

    The interactions between two heme proteins myoglobin (HMb) and horseradish peroxidase (HRP) with zinc oxide (ZnO) nanoparticles are investigated by using UV-vis absorption, steady state fluorescence, synchronous fluorescence, time-resolved fluorescence, FT-IR, atomic force microscopy (AFM) and circular dichroism (CD) techniques under physiological condition of pH˜7.4. The presence of mainly static mode in fluorescence quenching mechanism of HMb and HRP by ZnO nanoparticle indicates the possibility of formation of ground state complex. The processes of bindings of ZnO nanoparticles with the two proteins are spontaneous molecular interaction procedures. In both cases hydrogen bonding plays a major role. The circular dichroism (CD) spectra reveal that a helicity of the proteins is reduced by increasing ZnO nanoparticle concentration although the α-helical structures of HMb and HRP retain their identity. On binding to the ZnO nanoparticles the secondary structure of HRP molecules (or HMb molecules) remains unchanged while there is a substantial change in the environment of the tyrosin active site in case of HRP molecules and tryptophan active site in case of HMb molecules. Tapping mode atomic force microscopy (AFM) was applied for the investigation the structure of HRP adsorbed in the environment of nanoparticles on the silicon and on the bare silicon. HRP molecules adsorb and aggregate on the mica with ZnO nanoparticle. The aggregation indicates an attractive interaction among the adsorbed molecules. The molecules are randomly distributed on the bare silicon wafer. The adsorption of HRP in the environment of ZnO nanoparticle changes drastically the domains due to a strong interaction between HRP and ZnO nanoparticles. Similar situation is observed in case of HMb molecules. These findings demonstrate the efficacy of biomedical applications of ZnO nanoparticles as well as in elucidating their mechanisms of action as drugs in both human and plant systems.

  12. CAA modeling of helicopter main rotor in hover

    NASA Astrophysics Data System (ADS)

    Kusyumov, Alexander N.; Mikhailov, Sergey A.; Batrakov, Andrey S.; Kusyumov, Sergey A.; Barakos, George

    In this work rotor aeroacoustics in hover is considered. Farfield observers are used and the nearfield flow parameters are obtained using the in house HMB and commercial Fluent CFD codes (identical hexa-grids are used for both solvers). Farfield noise at a remote observer position is calculated at post processing stage using FW-H solver implemented in Fluent and HMB. The main rotor of the UH-1H helicopter is considered as a test case for comparison to experimental data. The sound pressure level is estimated for different rotor blade collectives and observation angles.

  13. Benzothiazolium Single Crystals: A New Class of Nonlinear Optical Crystals with Efficient THz Wave Generation.

    PubMed

    Lee, Seung-Heon; Lu, Jian; Lee, Seung-Jun; Han, Jae-Hyun; Jeong, Chan-Uk; Lee, Seung-Chul; Li, Xian; Jazbinšek, Mojca; Yoon, Woojin; Yun, Hoseop; Kang, Bong Joo; Rotermund, Fabian; Nelson, Keith A; Kwon, O-Pil

    2017-08-01

    Highly efficient nonlinear optical organic crystals are very attractive for various photonic applications including terahertz (THz) wave generation. Up to now, only two classes of ionic crystals based on either pyridinium or quinolinium with extremely large macroscopic optical nonlinearity have been developed. This study reports on a new class of organic nonlinear optical crystals introducing electron-accepting benzothiazolium, which exhibit higher electron-withdrawing strength than pyridinium and quinolinium in benchmark crystals. The benzothiazolium crystals consisting of new acentric core HMB (2-(4-hydroxy-3-methoxystyryl)-3-methylbenzo[d]thiazol-3-ium) exhibit extremely large macroscopic optical nonlinearity with optimal molecular ordering for maximizing the diagonal second-order nonlinearity. HMB-based single crystals prepared by simple cleaving method satisfy all required crystal characteristics for intense THz wave generation such as large crystal size with parallel surfaces, moderate thickness and high optical quality with large optical transparency range (580-1620 nm). Optical rectification of 35 fs pulses at the technologically very important wavelength of 800 nm in 0.26 mm thick HMB crystal leads to one order of magnitude higher THz wave generation efficiency with remarkably broader bandwidth compared to standard inorganic 0.5 mm thick ZnTe crystal. Therefore, newly developed HMB crystals introducing benzothiazolium with extremely large macroscopic optical nonlinearity are very promising materials for intense broadband THz wave generation and other nonlinear optical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Direct, simple derivatization of disulfide bonds in proteins with organic mercury in alkaline medium without any chemical pre-reducing agents.

    PubMed

    Campanella, Beatrice; Onor, Massimo; Ferrari, Carlo; D'Ulivo, Alessandro; Bramanti, Emilia

    2014-09-16

    In this work we have studied the derivatization of protein disulfide bonds with p-Hydroxymercurybenzoate (pHMB) in strong alkaline medium without any preliminary reduction. The reaction has been followed by the determination of the protein-pHMB complex using size exclusion chromatography coupled to a microwave/UV mercury oxidation system for the on-line oxidation of free and protein-complexed pHMB and atomic fluorescence spectrometry (SEC-CVG-AFS) detection. The reaction has been optimized by an experimental design using lysozyme as a model protein and applied to several thiolic proteins. The proposed method reports, for the first time, that it is possible to label 75-100% cysteines of proteins and, thus, to determine thiolic proteins without the need of any reducing step to obtain reduced SH groups before mercury labelling. We obtained a detection limit of 100 nmol L(-1) based on a signal-to-noise ratio of 3 for unbound and complexed pHMB, corresponding to a detection limit of proteins ranged between 3 and 360 nmol L(-1), depending on the number of cysteines in the protein sequence.

  15. Effect of feeding different sources of rumen-protected methionine on milk production and N-utilization in lactating dairy cows

    USDA-ARS?s Scientific Manuscript database

    Objectives of this study were to quantify production responses of lactating dairy cows to supplying absorbable Met as isopropyl-2-hydroxy-4-(methylthio)-butanoic acid (HMBi), or rumen-protected Met (RPM, Smartamine® M) fed with or without 2-hydroxy-4-(methylthio)-butanoic acid (HMB), and to determin...

  16. Solar Cycle Variations in Polar Cap Area Measured by the SuperDARN Radars

    NASA Astrophysics Data System (ADS)

    Imber, S. M.; Milan, S. E.; Lester, M.

    2013-12-01

    We present a long term study, from January 1996 - August 2012, of the latitude of the Heppner-Maynard Boundary (HMB) measured at midnight using the northern hemisphere SuperDARN radars. The HMB represents the equatorward extent of ionospheric convection, and is used in this study as a measure of the global magnetospheric dynamics and activity. We find that the yearly distribution of HMB latitudes is single-peaked at 64° magnetic latitude for the majority of the 17-year interval. During 2003 the envelope of the distribution shifts to lower latitudes and a second peak in the distribution is observed at 61°. The solar wind-magnetosphere coupling function derived by Milan et al. (2012) suggests that the solar wind driving during this year was significantly higher than during the rest of the 17-year interval. In contrast, during the period 2008-2011 HMB distribution shifts to higher latitudes, and a second peak in the distribution is again observed, this time at 68° magnetic latitude. This time interval corresponds to a period of extremely low solar wind driving during the recent extreme solar minimum. This is the first statistical study of the polar cap area over an entire solar cycle, and the results demonstrate that there is a close relationship between the phase of the solar cycle and the area of the polar cap on a large scale statistical basis.

  17. The Determination of Molecular Quantities from Measurements on Macroscopic Systems.V. Existence and Properties of 1:1 and 2:1-Electron-Donor-Acceptor Complexes of Hexamethylbenzene with Tetracyanoethylene

    NASA Astrophysics Data System (ADS)

    Liptay, Wolfgang; Rehm, Torsten; Wehning, Detlev; Schanne, Lothar; Baumann, Wolfram; Lang, Werner

    1982-12-01

    The formation of electron-donor-acceptor complexes of hexamethylbenzene (HMB) with tetracyanoethylene (TCNE) was investigated by measurements of the optical absorptions, the densities, the permittivities and the electro-optical absorptions of solutions in CCl4. The careful evaluation of data based on some previously reported models, has shown that the assumption of the formation of the 1: 1 and the 2 : 1 complex agrees with all experimental data, but that the assumption of the formation of only the 1: 1 complex is contradictory to experimental facts even if the activity effects on the equilibrium constant and of the solvent dependences of observed molar quantities are taken into account. The evaluation leads to the molar optical absorption coefficients and the molar volumes of both complexes and to their electric dipole moments in the electronic ground state and the considered excited state. According to these results the complexes are of the sandwich type HMB-TCNE and HMB-TCNE-HMB. In spite of the fact that the 2: 1 complex owns a center of symmetry, at least approximately, there is a rather large electric dipole moment in its excited state. Furthermore, values for the equilibrium constants and for the standard reaction enthalpies of both complex formation reactions are estimated from experimental data.

  18. Bleeding patterns with the levonorgestrel-releasing intrauterine system when used for heavy menstrual bleeding in women without structural pelvic pathology: a pooled analysis of randomized controlled studies.

    PubMed

    Jensen, Jeffrey; Mansour, Diana; Lukkari-Lax, Eeva; Inki, Pirjo; Burock, Karin; Fraser, Ian S

    2013-01-01

    The study was conducted to characterize the changes in bleeding pattern over time in women receiving the levonorgestrel-releasing intrauterine system (LNG-IUS) for heavy menstrual bleeding (HMB). The reduction in menstrual blood loss volume has been well documented elsewhere. Post hoc pooled analysis of the impact of the LNG-IUS on bleeding patterns in four comparator studies of medical and surgical treatment options for HMB. We enrolled women aged ≥18 years with HMB without organic pathology. The change in the number of bleeding and spotting (B/S) days and bleeding patterns was assessed over the duration of the studies pooled. One hundred and sixty-three women received the LNG-IUS in randomized trials. Relative to pretreatment baseline, there was a transient increase in the mean number of bleeding days in the first month of treatment, which returned to baseline by the second month and declined thereafter. Although the number of spotting days also increased during the first month of treatment, these declined with continued use but remained elevated relative to baseline during the first year of treatment. In women with HMB, the LNG-IUS is associated with an initial increase in number of B/S days that improve over time. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. The knowns and unknowns of human milk banking.

    PubMed

    Simmer, Karen

    2011-01-01

    The provision of donor human milk instead of formula is an important contribution to the nutrition and protection from infections for preterm infants. Systematic reviews suggest a lower risk of necrotizing enterocolitis with pasteurized donor human milk (PDHM) as opposed to artificial formula, although evidence supporting PDHM use from randomized control trials is limited. Human milk banks (HMBs) must have a risk management system to maintain a safe product especially as many operate in an unregulated environment. To ensure safety, the HMB in Australia has committed to meet the appropriate standards recommended in the Code of Good Manufacturing Practices (Blood and Tissues) and models risk management during processing on Codex HACCP (Hazard Analysis Critical Control Point) requirements. There is scope to continually reevaluate the screening of donors and quality standards recommended during HMB. This will be most effective if strong networks of HMBs are developed with regional reference laboratories to encourage compliance with safety guidelines. Further research and development is needed to refine technology for treating donor milk such as thermal ultrasound and ultraviolet light, aimed at the retention of full bioactivity. HMB networks will facilitate collection of evidence for refining HMB practice which should translate to improved outcomes for preterm and sick infants. Cost effectiveness is most likely when HMBs are associated with large neonatal intensive care units.

  20. CHIRONOMID EMERGENCE AND RELATIVE EMERGENT BIOMASS FROM TWO ALABAMA STREAMS

    EPA Science Inventory

    Chironomid pupal exuviae were sampled monthly using drift nets and hand sieves over an annual cycle from Hendrick Mill Branch (HMB; Blount County, AL) and Payne Creek (PC; Hale County, AL). Taxon richness, community composition, and emergence phonologies were similar despite mar...

  1. Randomized controlled trial of thermal balloon ablation versus vaginal hysterectomy for leiomyoma-induced heavy menstrual bleeding.

    PubMed

    Jain, Prachi; Rajaram, Shalini; Gupta, Bindiya; Goel, Neerja; Srivastava, Himsweta

    2016-11-01

    To compare the efficacy of thermal balloon ablation (TBA) with that of vaginal hysterectomy in the treatment of leiomyoma-induced heavy menstrual bleeding (HMB). An open-label randomized controlled trial was conducted between November 1, 2012, and October 31, 2014, in a tertiary care hospital in Delhi, India. Eligible women with HMB (aged ≥40 years, uterus size ≤14 weeks of pregnancy, leiomyoma ≤5 cm, uterocervical length ≤12 cm) were randomly assigned (1:1) to undergo TBA or vaginal hysterectomy using computer-generated random number tables. The primary outcome was the number of women in the TBA group with HMB 6 months after surgery. Analyses were by intention to treat. Each group contained 20 women. No women in the TBA group had HMB at 6 months. Nineteen women were amenorrheic by 6 months and one was hypomenorrheic. TBA can replace vaginal hysterectomy in some perimenopausal women with uterine leiomyomas. Clinical Trials Registry India: CTRI/2016/07/007119. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Influence of in ovo injection of disaccharides, glutamine and β-hydroxy-β-methylbutyrate on the development of small intestine in duck embryos and neonates.

    PubMed

    Chen, W; Wang, R; Xiong, X L; Wan, H F; Xu, J; Peng, J

    2010-10-01

    1. The objective of the present study was to examine the effect of in ovo injection of disaccharides (DS), disaccharides and glutamine (DS + Gln) or disaccharides and β-hydroxy-β-methylbutyrate (DS + HMB) at d 23 of incubation on the development of the small intestine. 2. In DS + Gln-injected ducks, the greatest relative small intestine mass and muscularis layer thickness among 4 treatments was observed from d 25 of incubation to 7 d of age. 3. Jejunal sucrase activity in DS-injected ducks was significantly greater than in controls at hatch and on d 7. 4. In DS + HMB-treated ducks, a tendency toward slightly higher jejunal DNA concentration was observed throughout the experiment. 5. Greater body weight was found in DS + Gln and DS + HMB treated ducks in the first two weeks. However, there was no significant difference in the market weight (35 d) of ducks among the 4 treatments. 6. The results of present study suggest that administering disaccharides and Gln, or disaccharides and HMB, to the duck embryos exerted a beneficial effect on the early development of small intestine and on growth performance.

  3. Direct Analysis of Leucine and Its Metabolites β-Hydroxy-β-methylbutyric Acid, α-Ketoisocaproic Acid, and α-Hydroxyisocaproic Acid in Human Breast Milk by Liquid Chromatography-Mass Spectrometry.

    PubMed

    Ehling, Stefan; Reddy, Todime M

    2015-09-02

    A direct, quantitative, and confirmatory method based on stable isotope dilution liquid chromatography-mass spectrometry was developed and validated for the analysis of leucine and metabolites β-hydroxy-β-methylbutyric acid (HMB), α-ketoisocaproic acid (KIC), and α-hydroxyisocaproic acid (HICA) in human breast milk. Chromatographic resolution was achieved between isobaric leucine and isoleucine. Accuracy and intermediate precision were 89-117% and <10% relative standard deviation (RSD) across three validation runs. Limits of quantitation for HMB, KIC, HICA, and leucine in human breast milk were 20 μg/L, 20 μg/L, 10 μg/L, and 1 mg/L. Measured concentrations of HMB, KIC, HICA, and free leucine in human breast milk from six donors at various stages of lactation were 42-164 μg/L, < 20-1057 μg/L, < 10 μg/L, and 2.1-88.5 mg/L. HMB and KIC were confirmed in human breast milk by orthogonal hydrophilic interaction chromatography (HILIC). This work provides a tool for further study of human breast milk composition and its effect on protein turnover in developing infants.

  4. CHIRONOMID EMERGENCE AND RELATIVE EMERGENT BIOMASS FROM TWO ALABAMA STREAMS

    EPA Science Inventory

    Chironomid pupal exuviae were sampled monthly using drift nets and hand sieves over an annual cycle from Hendrick Mill Branch (HMB; Blount County, AL) and Payne Creek (PC; Hale County, AL). Taxon richness, community composition, and emergence phonologies were similar despite mar...

  5. Heavy menstrual bleeding.

    PubMed

    Pearce, Lynne

    2016-10-05

    Essential facts Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss that interferes with a woman's physical, emotional, social or material quality of life. In England and Wales, around 80,000 women a year will be referred for the first time to secondary care, with 30,000 requiring surgical treatment.

  6. Levonorgestrel-Releasing Intrauterine Device Use in Female Adolescents with Heavy Menstrual Bleeding and Bleeding Disorders: Single Institution Review.

    PubMed

    Adeyemi-Fowode, Oluyemisi A; Santos, Xiomara M; Dietrich, Jennifer E; Srivaths, Lakshmi

    2017-08-01

    To identify complications and efficacy of the levonorgestrel-releasing intrauterine device (LNgIUD) in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD). A retrospective chart review of 13 postmenarchal adolescent girls with HMB/BD who underwent placement of an LNgIUD. Placement of an LNgIUD. Primary outcome was to identify complications from placement of an LNgIUD. Secondary outcome was to evaluate the efficacy of the LNgIUD in adolescents with BD. Thirteen patients met study criteria. The mean age of diagnosis of HMB was 14.08 ± 1.75 years. BD or bleeding risk factor diagnoses included low von Willebrand (VW) activity in 5, type I VW disease in 5, type IIM VW disease in 1, low VW activity and factor 7 deficiency in 1, and acquired VW disease and factor 7 deficiency in 1. Before LNgIUD placement, other hormonal therapy (n = 13) and hemostatic therapy (antifibrinolytic agents, desmopressin acetate; n = 8) yielded poor control of HMB. The LNgIUD was placed using anesthesia with periprocedure hemostatic therapy with no complications. All patients reported significant improvement in HMB after LNgIUD placement and 60% achieved amenorrhea, with mean time to improvement of 94 ± 69 days. Mean hemoglobin and ferritin levels increased after LNgIUD placement compared with before LNgIUD placement values (P = .02, P = .0085, respectively). Use of supplemental hormonal and hemostatic agents decreased (n = 4) after LNgIUD placement. None required LNgIUD removal; 1 spontaneously expelled the LNgIUD with subsequent replacement. Study results indicated the LNgIUD is an effective therapeutic option in postmenarchal adolescents with HMB due to BD/bleeding risk factor with minimal complications, high compliance rate, improvement in HMB and anemia, and no periprocedural bleeding with hemostatic management. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  7. The association between subjective assessment of menstrual bleeding and measures of iron deficiency anemia in premenopausal African-American women: a cross-sectional study.

    PubMed

    Bernardi, Lia A; Ghant, Marissa S; Andrade, Carolina; Recht, Hannah; Marsh, Erica E

    2016-08-15

    Both iron deficiency and iron deficiency anemia are common in the United States with a prevalence amongst women of 12 % and 4 % respectively. These numbers are even higher in African-American women (AAW) and are often a result of heavy menstrual bleeding (HMB). The primary objective of this study was to determine if perceived assessment of menstrual bleeding was associated with objective and subjective measures of anemia in AAW. Quantitative cross-sectional pilot study with surveys and venipuncture. 44 premenopausal AAW (mean age 37.9 years ± 9. 4) participated in the study. Iron deficiency was present in 68.2 % of the participants and 18.2 % were anemic. Almost half of the participants reported that their menses were heavy or very heavy, and there was a relationship between perceived heaviness of menstrual flow and anemia (P = 0.021). Of the individuals who reported that their menses were heavy or very heavy, 35.0 % were anemic. AAW who reported heavy or very heavy menses had significantly lower hemoglobin (P = 0.015), hematocrit (P = 0.003), and ferritin (P = 0.012) levels, as well as more general (P = 0.006) and menses-associated symptoms of anemia (P = 0.015) than those who reported normal or light menses. This pilot study of premenopausal AAW found that a significant percentage of women who report HMB are not only iron deficient, but also anemic. AAW should be educated on the consequences of HMB and counseled to seek care with a women's health provider when they perceive HMB. More importantly, providers should be aware that when AAW report HMB, evaluation for iron deficiency and anemia are essential.

  8. Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding: long-term randomised pragmatic trial in primary care

    PubMed Central

    Kai, Joe; Middleton, Lee; Daniels, Jane; Pattison, Helen; Tryposkiadis, Konstantinos; Gupta, Janesh

    2016-01-01

    Background Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. Aim To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. Design and setting A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. Method In total, 571 women aged 25–50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen–progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. Results At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = −0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Conclusion Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery. PMID:27884916

  9. Effects of zinc and sodium monensin on ruminal degradation of lysine-HCl and liquid 2-hydroxy-4-methylthiobutanoic acid.

    PubMed

    Bateman, H G; Williams, C C; Gantt, D T; Chung, Y H; Beem, A E; Stanley, C C; Goodier, G E; Hoyt, P G; Ward, J D; Bunting, L D

    2004-08-01

    Four nonlactating, mature, Holstein cows were fitted with ruminal cannula and used in a 4 x 4 Latin square-designed experiment to evaluate the impact of supplemental Zn and monensin on ruminal degradation of Lys and liquid 2-hydroxy-4-methylthiobutanoic acid (HMB). Cows were fed 4.54 kg (as fed) of alfalfa hay top-dressed with 4.54 kg (as fed) concentrate once daily. Concentrates were formulated to provide 0 or 500 mg/kg of Zn as ZnSO4 and 0 or 40 mg/kg of monensin in the total diet. Zinc supplementation provided approximately 22-fold greater dietary Zn than estimated by NRC requirements. On d 14 of each period, cows were dosed via the rumen cannula with 50 g of HMB and 100 g of Lys-HCl, and the concentrations of Lys and HMB were monitored every 0.5 h for 8 h. Supplemental Zn tended to decrease the proportion of acetate in ruminal fluid postfeeding and increased the proportion of propionate in ruminal fluid postfeeding. Supplemental Zn increased mean fluid passage rate from the rumen. Monensin decreased the proportion of acetate and increased the mean proportion of propionate in ruminal fluid, resulting in a decrease in the ratio of acetate to propionate. Monensin also increased the mean fluid passage rate from the rumen. Neither Zn nor monensin affected the apparent rate of ruminal disappearance of HMB or Lys. However, Zn and monensin interacted to alter the ruminal degradability of free Lys but not HMB. These data indicate that Zn and monensin may interact to alter ruminal degradability of free amino acids.

  10. Effect of β-hydroxy-β-methylbutyrate in masticatory muscles of rats.

    PubMed

    Daré, Leticia R; Dias, Daniel V; Rosa Junior, Geraldo M; Bueno, Cleuber R S; Buchaim, Rogerio L; Rodrigues, Antonio de C; Andreo, Jesus C

    2015-01-01

    The aim of this research was to examine the influence of β-hydroxy-β-methylbutyrate (HMB) on changes in the profile of muscle fibers, whether these alterations were similar between the elevator and depressor muscles of the jaw, and whether the effects would be similar in male and female animals. Fifty-eight rats aged 60 days (29 animals of each gender) were divided into four groups: the initial control group (ICG) was sacrificed at the beginning of the experiment; the placebo control group (PCG) received saline and was fed ad libitum; the experimental group (EG) received 0.3 g kg(-1) of HMB daily for 4 weeks by gavage as well as the same amount of food consumed by the PCG in the previous day; and the experimental ad libitum group (EAG) received the same dose of the supplement along with food ad libitum. Samples included the digastric and masseter muscles for the histoenzymological analysis. Data were subjected to statistical analysis with a significance level of P < 0.05. Use of HMB caused a decrease in the percentage of fast twitch glycolytic (FG) fibers and an increase in fast twitch oxidative glycolytic (FOG) fibers in males in both experimental groups (EG and EAG). However, it produced no increase in the muscle fiber area, in either gender, in the masseter muscle. In the digastric muscle, the HMB did not change the frequency or the area of any muscle fiber types in either gender. Our data suggest that the use of HMB caused small changes in the enzymological profile of fibers of the mastication muscles; the changes were different in the elevator and depressor muscles of the jaw and the results were different depending on gender. © 2014 Anatomical Society.

  11. A subset of fat-predominant angiomyolipomas label for MDM2: a potential diagnostic pitfall.

    PubMed

    Asch-Kendrick, Rebecca J; Shetty, Shashi; Goldblum, John R; Sharma, Rajni; Epstein, Jonathan I; Argani, Pedram; Cimino-Mathews, Ashley

    2016-11-01

    Angiomyolipomas (AMLs) are typically benign mesenchymal tumors with variable histologic composition. Fat-predominant AMLs can mimic well-differentiated liposarcomas (WDLSs) both radiographically and histologically because of the abundance of fat with admixed atypical cells resembling lipoblasts. However, the treatment and prognosis of AMLs and WDLSs are vastly different. Immunohistochemistry for murine double minute 2 (MDM2) has been used to support a diagnosis of WDLS; however, MDM2 labeling has not been specifically evaluated in fat-predominant AMLs. Here, we evaluated MDM2 immunohistochemistry in 36 AMLs (including 14 conventional AMLs, 13 fat-predominant AMLs, 6 fat-rich AMLs, 3 epithelioid AMLs) and 10 WDLSs. In addition, we labeled cases for HMB45, calponin, or actin, which are immunostains traditionally used to label AML. We performed fluorescence in situ hybridization (FISH) for MDM2 amplification on selected cases. By immunohistochemistry, 14% (5/36) of AMLs were MDM2+, including 23% (3/13) of fat-predominant AMLs. All MDM2+ AMLs evaluated by FISH (n=4) were negative for MDM2 amplification. By immunohistochemistry, 90% of WDLSs were MDM2+, and both MDM2+ WDLSs evaluated by FISH (n=2) were MDM2 amplified. All 36 AMLs labeled with HMB45 and calponin or actin. No WDLS labeled with HMB45; however, 80% of WDLSs labeled with calponin or actin. Although uncommon, MDM2 labeling is seen in a subset of fat-predominant AMLs and is a potential diagnostic pitfall in the evaluation of fatty tumors of the retroperitoneum. HMB45 is more sensitive and specific for AML than calponin or actin, and an immunopanel containing both HMB45 and MDM2 may be warranted to distinguish between fat-predominant AML and WDLS in histologically ambiguous cases. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Rapid immunohistochemistry of sentinel lymph nodes for metastatic melanoma.

    PubMed

    Eudy, Grant E; Carlson, Grant W; Murray, Douglas R; Waldrop, Sandra M; Lawson, Dianne; Cohen, Cynthia

    2003-08-01

    Sentinel lymph node (SLN) biopsy is performed on patients with malignant melanoma (MM) to assess the need for selective complete lymphadenectomy. Melanoma metastasis to regional lymph nodes is an important prognostic indicator in patients with MM. This study assesses the sensitivity and specificity of rapid immunohistochemistry (RIHC) in intraoperative delineation of melanoma metastasis to SLN. RIHC for S-100 protein, HMB45, and a melanoma marker cocktail (melan A, HMB45, and tyrosinase) was performed on 71 SLNs obtained from 28 patients with MM. Frozen sections (6 micro thick) on plus slides were fixed for 2 to 3 minutes in cold acetone and then stored at -70 degrees C. The EnVision kit (Dako, Carpinteria, CA) for rapid immunohistochemistry (RIHC) on frozen tissue sections was used, and the staining technique took 19 minutes. Together with preparation of the frozen sections and fixation in acetone, immunostained slides were available in approximately 25 minutes. Of the 71 SNLs examined, 7 showed melanoma metastasis in permanent sections. RIHC of frozen sections detected metastatic melanoma in 6 SLNs, with a sensitivity of 86% for HMB45 and 71% for S-100 protein and the melanoma cocktail and a specificity of 97% for HMB45 and 100% for S-100 and the melanoma cocktail. We conclude that RIHC for HMB45, S-100 protein, and the melanoma cocktail may help detect melanoma metastasis in SLN intraoperatively, leading to total lymph node dissection and obviating the need for 2 surgical procedures. Section folds and background stain can make interpretation difficult. Intraoperative time constraints require a more rapid technique. A recent consensus group has discouraged frozen-section examination of SLN.

  13. Production of proinflammatory cytokines without invocation of cytotoxic effects by an Epstein-Barr virus-infected natural killer cell line established from a patient with hypersensitivity to mosquito bites.

    PubMed

    Suzuki, Daisuke; Tsuji, Kazuhide; Yamamoto, Takenobu; Fujii, Kazuyasu; Iwatsuki, Keiji

    2010-10-01

    Cumulative evidence supports that Epstein-Barr virus (EBV)-infected natural killer (NK) cells induce severe systemic and cutaneous inflammation in patients with hypersensitivity to mosquito bites (HMB). In order to understand the pathogenesis of HMB, we established an EBV-infected cell line and characterized the cytological profiles. A novel EBV-infected NK-cell line, designated NKED, was established from a patient with HMB and used for the present study along with two other NK-cell lines, KAI3 and KHYG-1. NKED expressed the latency II-related transcripts. NKED cells were positive for CD2 and CD161 antigens, and negative for CD3, CD16, CD34, CD56, and T-cell receptor α/β and γ/δ antigens. Although NKED cells contained several cytotoxic molecules, the cells had an extremely poor cytotoxic activity. The majority of NKED cells were negative for perforin, major histocompatibility complex class I-restricted NK-cell receptors, CD94 and KIR2D, and an activating receptor, NKG2D. NKED cells, however, secreted higher levels of tumor necrosis factor-α. Stimulation with phorbol 12-myristate 13-acetate or tumor necrosis factor-α induced expression of BZLF1 messenger RNA in the NKED and KAI3 cells, indicating the transition from the latent- to the lytic-cycle infection. These data suggested that NKED cells revealed a very low cytotoxic effect probably because of the low expression levels of perforin, but had the ability to release proinflammatory cytokines. NKED cells did not reflect the characteristics of HMB, as they were different from pathogenic NK cells proliferating in the HMB patient, but the difference indicated that pathogenic NK cells could change their character in the presence of interleukin-2. Copyright © 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  14. Identification and expression of mutations in the hydroxymethylbilane synthase gene causing acute intermittent porphyria (AIP).

    PubMed Central

    Solis, C.; Lopez-Echaniz, I.; Sefarty-Graneda, D.; Astrin, K. H.; Desnick, R. J.

    1999-01-01

    BACKGROUND: Acute intermittent porphyria (AIP), an autosomal dominant inborn error, results from the half-normal activity of the heme biosynthetic enzyme hydroxymethylbilane synthase (EC 4.3.1.8; HMB-synthase). This disease is characterized by acute, life-threatening neurologic attacks that are precipitated by various drugs, hormones, and other factors. The enzymatic and/or biochemical diagnosis of AIP heterozygotes is problematic; therefore, efforts have focused on the identification of HMB-synthase mutations so that heterozygotes can be identified and educated to avoid the precipitating factors. In Spain, the occurrence of AIP has been reported, but the nature of the HMB-synthase mutations causing AIP in Spanish families has not been investigated. Molecular analysis was therefore undertaken in nine unrelated Spanish AIP patients. MATERIALS AND METHODS: Genomic DNA was isolated from affected probands and family members of nine unrelated Spanish families with AIP. The HMB-synthase gene was amplified by long-range PCR and the nucleotide sequence of each exon was determined by cycle sequencing. RESULTS: Three new mutations, a missense, M212V; a single base insertion, g4715insT; and a deletion/insertion, g7902ACT-->G, as well as five previously reported mutations (G111R, R116W, R149X R167W, and R173W) were detected in the Spanish probands. Expression of the novel missense mutation M212V in E. coli revealed that the mutation was causative, having <2% residual activity. CONCLUSIONS: These studies identified the first mutations in the HMB-synthase gene causing AIP in Spanish patients. Three of the mutations were novel, while five previously reported lesions were found in six Spanish families. These findings enable accurate identification and counseling of presymptomatic carriers in these nine unrelated Spanish AIP families and further demonstrate the genetic heterogeneity of mutations causing AIP. Images Fig. 1 PMID:10602775

  15. Effect of β-hydroxy-β-methylbutyrate in masticatory muscles of rats

    PubMed Central

    Daré, Leticia R; Dias, Daniel V; Rosa Junior, Geraldo M; Bueno, Cleuber R S; Buchaim, Rogerio L; Rodrigues, Antonio de C; Andreo, Jesus C

    2015-01-01

    The aim of this research was to examine the influence of β-hydroxy-β-methylbutyrate (HMB) on changes in the profile of muscle fibers, whether these alterations were similar between the elevator and depressor muscles of the jaw, and whether the effects would be similar in male and female animals. Fifty-eight rats aged 60 days (29 animals of each gender) were divided into four groups: the initial control group (ICG) was sacrificed at the beginning of the experiment; the placebo control group (PCG) received saline and was fed ad libitum; the experimental group (EG) received 0.3 g kg−1 of HMB daily for 4 weeks by gavage as well as the same amount of food consumed by the PCG in the previous day; and the experimental ad libitum group (EAG) received the same dose of the supplement along with food ad libitum. Samples included the digastric and masseter muscles for the histoenzymological analysis. Data were subjected to statistical analysis with a significance level of P < 0.05. Use of HMB caused a decrease in the percentage of fast twitch glycolytic (FG) fibers and an increase in fast twitch oxidative glycolytic (FOG) fibers in males in both experimental groups (EG and EAG). However, it produced no increase in the muscle fiber area, in either gender, in the masseter muscle. In the digastric muscle, the HMB did not change the frequency or the area of any muscle fiber types in either gender. Our data suggest that the use of HMB caused small changes in the enzymological profile of fibers of the mastication muscles; the changes were different in the elevator and depressor muscles of the jaw and the results were different depending on gender. PMID:25400135

  16. A (14)C-leucine absorption, distribution, metabolism and excretion (ADME) study in adult Sprague-Dawley rat reveals β-hydroxy-β-methylbutyrate as a metabolite.

    PubMed

    Lee, Anthony J; Beno, David W A; Zhang, Xiaolin; Shapiro, Robin; Mason, Mark; Mason-Bright, Tanita; Surber, Bruce; Edens, Neilé K

    2015-05-01

    Leucine is an essential branched-chain amino acid that acts as a substrate for protein synthesis and as a signaling molecule. Leucine not incorporated into muscle protein is ultimately oxidized through intermediates such as β-hydroxy-β-methylbutyrate (HMB) which itself is reported to enhance muscle mass and function in rats and humans. HMB has been reported in the plasma following oral leucine administration in sheep and pigs but not in Sprague-Dawley rats, the standard preclinical model. Therefore, we conducted radiolabeled absorption, distribution, metabolism and excretion (ADME) studies in rats using a low (3 mg/kg) or high dose (1,000 mg/kg) of (14)C-leucine. Blood, tissue, and urine samples were analyzed for (14)C-leucine and its metabolites by HPLC-MS. Our results show for the first time that (14)C-HMB appears in plasma and urine of rats following an oral dose of (14)C-leucine. (14)C-leucine appears in plasma as (14)C-α-ketoisocaproic acid (KIC) with a slower time course than (14)C-HMB, a putative product of KIC. Further, two novel metabolites of leucine were detected in urine, N-acetyl leucine and glycyl leucine. Mass balance studies demonstrate that excretory routes accounted for no more than 0.9 % of the radiolabel and approximately 61 % of the dose was recovered in the carcass. Approximately 65 % of the dose was recovered in total, suggesting that approximately one-third of the leucine dose is oxidized to CO2. In conclusion, this study demonstrates endogenous production of HMB from leucine in adult rats, a standard preclinical model used to guide design of clinical trials in nutrition.

  17. Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding: long-term randomised pragmatic trial in primary care.

    PubMed

    Kai, Joe; Middleton, Lee; Daniels, Jane; Pattison, Helen; Tryposkiadis, Konstantinos; Gupta, Janesh

    2016-12-01

    Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. In total, 571 women aged 25-50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen-progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = -0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery. © British Journal of General Practice 2016.

  18. Effects of two training protocols on the forehand drive performance in tennis.

    PubMed

    Genevois, Cyril; Frican, Baptiste; Creveaux, Thomas; Hautier, Christophe; Rogowski, Isabelle

    2013-03-01

    The aim of this study was to examine the effects of 2 training modalities on the tennis forehand drive performance. Forty-four tennis players (mean ± SD: age = 26.9 ± 7.5 years; height = 178.6 ± 6.7 cm; mass = 72.5 ± 8.0 kg; International Tennis Number = 3) were randomly assigned into 3 groups. During 6 weeks, the first group performed handled medicine ball (HMB) throws included in the regular tennis practice, the second group (overweight racket-OWR) played tennis forehand drives with an overweighed racket during the regular tennis practice, and the third group (regular tennis training-RTT) practiced only tennis training as usual. Before and after the 6-week program, velocity and accuracy of tennis crosscourt forehand drives were evaluated in the 3 groups. The main results showed that after 6-week training, the maximal ball velocity was significantly increased in HMB and OWR groups in comparison with RTT (p < 0.001 and p = 0. 001, respectively). The estimated averaged increase in ball velocity was greater in HMB than in OWR (11 vs. 5%, respectively; p = 0.017), but shot accuracy tended to be deteriorated in HMB when compared with OWR and RTT (p = 0.043 and p = 0.027, respectively). The findings of this study highlighted the efficiency of both training modalities to improve tennis forehand drive performance but also suggested that the HMB throws may be incorporated into the preseason program preferably, whereas the OWR forehand drives may be included in the on-season program.

  19. Mitigation of Salmonella on Pet Food Kibbles by Using Liquid and Powdered 3-Hydroxy-3-Methylbutyric Acid.

    PubMed

    Huss, Anne R; Fuller, John C; Centrella, William; Marshall, Douglas L; Deliephan, Aiswariya; Jones, Cassandra K

    2017-07-01

    In recent years, several pet food recalls have been attributed to Salmonella contamination. In addition to the negative impacts on animal health, Salmonella-contaminated pet foods have been linked to infection in humans. With that in mind, the U.S. Food and Drug Administration has set forth a zero-tolerance policy for Salmonella in pet foods. Typically, pet foods are extruded or processed at high temperatures that are sufficient to reduce pathogenic bacteria. However, the possibility for postextrusion contamination still exists. One potential method to reduce the risk of postextrusion contamination of pet foods with Salmonella is through the addition of a chemical additive coating. The objective of this research was to evaluate the ability of β-hydroxy-β-methylbutyrate (HMB), in either free acid (HMBFA) or calcium salt (CaHMB) form, to reduce postextrusion contamination of dry extruded dog kibble with Salmonella. Three trials were conducted with HMBFA and CaHMB coated onto the kibbles at levels of 0, 0.1, 0.3, 0.5, 0.9, and 1.5% (w/w). The coated kibbles were then inoculated with Salmonella enterica subsp. enterica Enteritidis (ATCC 13076), with enumeration done on days 0, 1, 2, 7, and 14 postinoculation. Subsamples on each day were serially diluted, spread plated to xylose lysine deoxycholate agar, and incubated at 37°C for 24 h. Salmonella colonies were then counted and log CFU per gram was calculated. The 1.5% HMBFA reduced counts by 4.9 ± 0.2 log units on day 1, whereas the positive control only decreased 2.2 ± 0.1 log units (P < 0.0001). The 1.5% CaHMB level decreased counts by 7.1 ± 0.04 log units by day 7 compared with the control decrease of 2.1 ± 0.1 log units (P < 0.0001). All HMBFA and CaHMB treatments resulted in the elimination of detectable Salmonella counts by day 14 (P < 0.0001 versus controls). In conclusion, HMB coating was effective at reducing Salmonella artificially inoculated to dog kibbles in a model of postextrusion contamination.

  20. Highly Active Microbial Phosphoantigen Induces Rapid yet Sustained MEK/Erk- and PI-3K/Akt-Mediated Signal Transduction in Anti-Tumor Human γδ T-Cells

    PubMed Central

    Cardoso, Bruno A.; Lança, Telma; Grosso, Ana R.; deBarros, Ana; Martins, Leila R.; Barata, João T.; Silva-Santos, Bruno

    2009-01-01

    Background The unique responsiveness of Vγ9Vδ2 T-cells, the major γδ subset of human peripheral blood, to non-peptidic prenyl pyrophosphate antigens constitutes the basis of current γδ T-cell-based cancer immunotherapy strategies. However, the molecular mechanisms responsible for phosphoantigen-mediated activation of human γδ T-cells remain unclear. In particular, previous reports have described a very slow kinetics of activation of T-cell receptor (TCR)-associated signal transduction pathways by isopentenyl pyrophosphate and bromohydrin pyrophosphate, seemingly incompatible with direct binding of these antigens to the Vγ9Vδ2 TCR. Here we have studied the most potent natural phosphoantigen yet identified, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), produced by Eubacteria and Protozoa, and examined its γδ T-cell activation and anti-tumor properties. Methodology/Principal Findings We have performed a comparative study between HMB-PP and the anti-CD3ε monoclonal antibody OKT3, used as a reference inducer of bona fide TCR signaling, and followed multiple cellular and molecular γδ T-cell activation events. We show that HMB-PP activates MEK/Erk and PI-3K/Akt pathways as rapidly as OKT3, and induces an almost identical transcriptional profile in Vγ9+ T-cells. Moreover, MEK/Erk and PI-3K/Akt activities are indispensable for the cellular effects of HMB-PP, including γδ T-cell activation, proliferation and anti-tumor cytotoxicity, which are also abolished upon antibody blockade of the Vγ9+ TCR Surprisingly, HMB-PP treatment does not induce down-modulation of surface TCR levels, and thereby sustains γδ T-cell activation upon re-stimulation. This ultimately translates in potent human γδ T-cell anti-tumor function both in vitro and in vivo upon transplantation of human leukemia cells into lymphopenic mice, Conclusions/Significance The development of efficient cancer immunotherapy strategies critically depends on our capacity to maximize anti

  1. Human Neutrophil Clearance of Bacterial Pathogens Triggers Anti-Microbial γδ T Cell Responses in Early Infection

    PubMed Central

    Roberts, Gareth W.; Heuston, Sinéad; Brown, Amanda C.; Chess, James A.; Toleman, Mark A.; Gahan, Cormac G. M.; Hill, Colin; Parish, Tanya; Williams, John D.; Davies, Simon J.; Johnson, David W.; Topley, Nicholas; Moser, Bernhard; Eberl, Matthias

    2011-01-01

    Human blood Vγ9/Vδ2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vγ9/Vδ2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vγ9/Vδ2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vγ9/Vδ2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-α dependent proliferation of Vγ9/Vδ2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting γδ T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vγ9/Vδ2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The γδ T cell-driven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of γδ T cells and TNF-α and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive γδ T cells in early

  2. Human neutrophil clearance of bacterial pathogens triggers anti-microbial γδ T cell responses in early infection.

    PubMed

    Davey, Martin S; Lin, Chan-Yu; Roberts, Gareth W; Heuston, Sinéad; Brown, Amanda C; Chess, James A; Toleman, Mark A; Gahan, Cormac G M; Hill, Colin; Parish, Tanya; Williams, John D; Davies, Simon J; Johnson, David W; Topley, Nicholas; Moser, Bernhard; Eberl, Matthias

    2011-05-01

    Human blood Vγ9/Vδ2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vγ9/Vδ2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vγ9/Vδ2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vγ9/Vδ2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-α dependent proliferation of Vγ9/Vδ2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting γδ T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis--characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity--show a selective activation of local Vγ9/Vδ2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The γδ T cell-driven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of γδ T cells and TNF-α and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive γδ T cells in early

  3. Studies on the oxidation of hexamethylbenzene 1: Oxidation of hexamethylbenzene with nitric acid

    NASA Technical Reports Server (NTRS)

    Chiba, K.; Tomura, S.; Mizuno, T.

    1986-01-01

    The oxidative reaction of hexamethylbenzene (HMB) with nitric acid was studied, and the hitherto unknown polymethylbenzenepolycarboxylic acids were isolated: tetramethylphthalic anhydride, tetramethylisophthalic acid, 1,3,5-, 1,2,4- and 1,2,3-trimethylbenzenetricarboxylic acids. When HMB was warmed with 50% nitric acid at about 80 C, tetramethylphthalic anhydride and tetramethylisophthalic acid were initially produced. The continued reaction led to the production of trimethylbenzenetricarboxylic acids, but only slight amounts of dimethylbenzenetetracarboxylic acids were detected in the reaction mixture. Whereas tetramethylphthalic anydride and tetramethylisophthalic acid were obtained, pentamethylbenzoic acid, a possible precursor of them, was scarcely produced. On the other hand, a yellow material extracted with ether from the initial reaction mixture contained bis-(nitromethyl)prehnitene (CH3)4C6(CH2NO2)2, which was easily converted into the phthalic anhydride.

  4. Submucosal uterine fibroid prolapsed into vagina in a symptomatic patient with IUS

    PubMed Central

    Matytsina-Quinlan, Lyubov; Matytsina, Laura

    2014-01-01

    A female patient in her mid 40s presents with heavy menstrual bleeding (HMB) and a history of spotting/irregular light per vagina (PV) bleeding since intrauterine system (IUS) insertion 1 year ago. She is known to have submucosal uterine fibroid (SMUF). The patient reported abdominal pain and sudden onset of ‘miscarriage-like’ HMB with clots 2 days ago. On speculum examination there was a smooth round-shaped mass lying over the external cervical os. On bimanual examination PV, a round-shaped smooth mass of a walnut's size was palpable in the upper third of the vagina. Subsequent ultrasound imaging revealed an SMUF prolapsed into the vagina. Further surgical treatment was undertaken. Histology showed a fibroid (leiomyoma) with no evidence of malignancy. PMID:24739657

  5. Genomic Hotspots for Adaptation: The Population Genetics of Müllerian Mimicry in the Heliconius melpomene Clade

    PubMed Central

    Baxter, Simon W.; Nadeau, Nicola J.; Maroja, Luana S.; Wilkinson, Paul; Counterman, Brian A.; Dawson, Anna; Beltran, Margarita; Perez-Espona, Silvia; Chamberlain, Nicola; Ferguson, Laura; Clark, Richard; Davidson, Claire; Glithero, Rebecca; Mallet, James; McMillan, W. Owen; Kronforst, Marcus; Joron, Mathieu; ffrench-Constant, Richard H.; Jiggins, Chris D.

    2010-01-01

    Wing patterning in Heliconius butterflies is a longstanding example of both Müllerian mimicry and phenotypic radiation under strong natural selection. The loci controlling such patterns are “hotspots” for adaptive evolution with great allelic diversity across different species in the genus. We characterise nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium, and candidate gene expression at two loci and across multiple hybrid zones in Heliconius melpomene and relatives. Alleles at HmB control the presence or absence of the red forewing band, while alleles at HmYb control the yellow hindwing bar. Across HmYb two regions, separated by ∼100 kb, show significant genotype-by-phenotype associations that are replicated across independent hybrid zones. In contrast, at HmB a single peak of association indicates the likely position of functional sites at three genes, encoding a kinesin, a G-protein coupled receptor, and an mRNA splicing factor. At both HmYb and HmB there is evidence for enhanced linkage disequilibrium (LD) between associated sites separated by up to 14 kb, suggesting that multiple sites are under selection. However, there was no evidence for reduced variation or deviations from neutrality that might indicate a recent selective sweep, consistent with these alleles being relatively old. Of the three genes showing an association with the HmB locus, the kinesin shows differences in wing disc expression between races that are replicated in the co-mimic, Heliconius erato, providing striking evidence for parallel changes in gene expression between Müllerian co-mimics. Wing patterning loci in Heliconius melpomene therefore show a haplotype structure maintained by selection, but no evidence for a recent selective sweep. The complex genetic pattern contrasts with the simple genetic basis of many adaptive traits studied previously, but may provide a better model for most adaptation in natural populations that has arisen over

  6. The relationship of melanocytic differentiation with prognostic markers in medullary thyroid carcinomas.

    PubMed

    Karaarslan, Serap; Nur Yurum, Fatma; Ebru Pala, Emel; Ortac, Ragip; Husnu Bugdayci, Mehmet

    2015-05-01

    Medullary thyroid carcinoma (MTC) makes up 5-10% of thyroid malignancies. Small cell, squamous, giant cell or melanocytic differentiation can rarely be seen in MTCs. It is important to determine those with the potential to act aggressively such as cases with melanocytic differentiation at the time of diagnosis. A total of 46 MTC cases diagnosed at four different centers between 2002 and 2013 were included in the study. Immunohistochemical (IHC) staining with Melan-A and HMB-45 was performed in all cases. Six of the 46 MTC cases were medullary microcarcinomas and three were multicentric medullary carcinomas. There were 34 females and 12 males with a mean age at onset of 51.4 years and mean tumor diameter of 23.2mm. Lymph node metastasis (LNM) was found in 13 of the 38 cases that had data regarding the lymph nodes. Immunohistochemically, Melan A staining was seen in four cases. HMB45 staining was seen in four cases. A statistically significant relationship was found between LNM and diameter, Melan A expression (p=0.02, p=0.03 respectively) but there was no significant relationship with HMB45 expression (p=0.07). General survival data were present for 35 of the 46 cases. All cases without lymph node metastasis survived (21/21) while 8 of 11 cases with lymph node metastasis survived among cases with survival data; one case that was diffuse-strong positive for both HMB45 and Melan A was lost due to distant organ metastasis six months after the diagnosis. Should the possibility of melanocytic differentiation be evaluated in cases where melanocytic differentiation is not reflected in the morphology (lack of pigment) in MTCs? We did not come across a study on the subject in the English literature. The effect of melanocytic differentiation on the prognosis in MTCs should be investigated in larger series. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. Choice of primary outcomes evaluating treatment for heavy menstrual bleeding.

    PubMed

    Herman, M C; Penninx, Jpm; Geomini, P M; Mol, B W; Bongers, M Y

    2016-09-01

    Heavy menstrual bleeding (HMB) is a common problem with a variety of treatment options and many studies have been performed evaluating treatment effects. Consistency in the choice and definition of primary and secondary outcomes is important for the interpretation of data and for the synthesis of data in systematic reviews or individual patient data meta-analysis (IPDMA). To give insight into the primary endpoints and outcome measures chosen in randomised controlled trials (RCTs) and systematic reviews regarding the treatment of HMB. Published systematic reviews and RCTs. Full reports of RCTs or systematic reviews. For RCTs, we used the primary outcomes, as they were used for the sample size calculation. For systematic reviews, all outcomes listed as primary were included. Four authors selected the studies. Twelve different primary outcomes were reported by 66 RCTs, most blood loss- related (44/66 studies). Amenorrhoea was the most common blood loss primary outcome (16/44 studies) and the Pictorial Blood Loss Assessment Chart (PBAC) was the most used measurement tool (27/44 studies). Satisfaction was the second most prevalent primary outcome measure (13/66 studies). In all, 14/26 (54%) systematic reviews prespecified a single primary outcome, whereas all other reviews used composite primary outcomes. Blood loss was the most studied outcome (12/26 reviews). The most used primary outcomes in HMB studies relate to blood loss but there is no consistency regarding the endpoints chosen or measurement tools used to describe blood loss. Standardising outcomes will aid valid comparison and interpretation of data pertaining to the treatment of HMB. A standardised collection of outcomes in heavy menstrual bleeding research is urgently needed. © 2016 Royal College of Obstetricians and Gynaecologists.

  8. Epstein-Barr virus reactivation is induced, but abortive, in cutaneous lesions of systemic hydroa vacciniforme and hypersensitivity to mosquito bites.

    PubMed

    Yamamoto, Takenobu; Hirai, Yoji; Miyake, Tomoko; Hamada, Toshihisa; Yamasaki, Osamu; Morizane, Shin; Fujimoto, Wataru; Iwatsuki, Keiji

    2016-06-01

    Epstein-Barr virus (EBV)-associated T/natural killer (NK)-lymphoproliferative disorders (LPDs) include hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). The pathomechanisms of these diseases are still unclear. To understand the inflammatory process, we examined EBV reactivation markers, BZLF1 and BDRF1 mRNA in the tissue and blood from patients with EBV-associated T/NK-LPDs. Sixty-four patients with EBV-associated LPDs and epithelial neoplasms, and EBV+ cell line cells were studied. DNase-treated and resistant EBV DNA load in blood and cell culture supernatants were calculated. An EBV reactivation signal was analyzed in the tissue, blood and cell line cells. In the tissue, BZLF1 mRNA was detected in 5 of 6 (83%) samples of EBV+ epithelial neoplasms, 16 of 21 (76%) of EBV+ lymphomas, and 5 of 15 (33%) of systemic HV and/or HMB, but negative in all 15 patients with classical HV. In the blood, BZLF1 mRNA was detected in only one of 19 (5.3%) samples of EBV-associated T/NK-LPDs. A down-stream reactivation signal, BDRF1 mRNA was expressed in all 6 samples of EBV+ epithelial neoplasms, but it was positive in only one of 15 (6.7%) samples from systemic HV and HMB in the tissue. EBV+ T/NK-cell line cells treated with phorbol 12-myristate 13-acetate produced BZLF1 and BDRF1 mRNA, and encapsidated EBV DNA was detected in the culture supernatants of cell line cells. Stimulation-induced EBV reactivation occurred both in vivo and in vitro, but it was almost abortive in vivo. Reactivation-related EBV antigens might be responsible for induction of systemic HV and HMB. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Disordered expression of inhibitory receptors on the NK1-type natural killer (NK) leukaemic cells from patients with hypersensitivity to mosquito bites

    PubMed Central

    Seo, N; Tokura, Y; Ishihara, S; Takeoka, Y; Tagawa, S; Takigawa, M

    2000-01-01

    Recent studies have revealed the existence of a distinct type of NK cell leukaemia of the juvenile type, which presents with hypersensitivity to mosquito bites (HMB) as an essential clinical manifestation and is infected with clonal Epstein–Barr virus (EBV). This disorder is thus called HMB-EBV-NK disease and has been reported in Orientals, mostly from Japan. We investigated the profile of cytokine production and the expression of both types of NK inhibitory receptors, i.e. CD94 lectin-like dimers and killer-cell immunoglobulin-like receptors, in NK leukaemic cells from three patients with HMB-EBV-NK disease. It was found that freshly isolated NK leukaemic cells expressed mRNA for interferon-gamma (IFN-γ) and additionally produced IL-10 upon stimulation with IL-2, indicating that the NK cells were of NK1 type. More than 98% of NK cells from the patients bore CD94 at a higher level than did normal NK cells, whereas p70 or NKAT2, belonging to immunoglobulin-like receptor, was not expressed in those NK cells. Freshly isolated leukaemic NK cells transcribed mRNA for CD94-associated molecule NKG2C at an abnormally high level, and upon stimulation with IL-2 and/or IL-12 they expressed NKG2A as well. The disordered expression of these inhibitory receptors not only provides some insights into the pathogenesis of HMB-EBV-NK disease but also can be used as phenotypic markers for the diagnosis of this type of NK cell leukaemia. PMID:10844517

  10. Genomic hotspots for adaptation: the population genetics of Müllerian mimicry in the Heliconius melpomene clade.

    PubMed

    Baxter, Simon W; Nadeau, Nicola J; Maroja, Luana S; Wilkinson, Paul; Counterman, Brian A; Dawson, Anna; Beltran, Margarita; Perez-Espona, Silvia; Chamberlain, Nicola; Ferguson, Laura; Clark, Richard; Davidson, Claire; Glithero, Rebecca; Mallet, James; McMillan, W Owen; Kronforst, Marcus; Joron, Mathieu; Ffrench-Constant, Richard H; Jiggins, Chris D

    2010-02-05

    Wing patterning in Heliconius butterflies is a longstanding example of both Müllerian mimicry and phenotypic radiation under strong natural selection. The loci controlling such patterns are "hotspots" for adaptive evolution with great allelic diversity across different species in the genus. We characterise nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium, and candidate gene expression at two loci and across multiple hybrid zones in Heliconius melpomene and relatives. Alleles at HmB control the presence or absence of the red forewing band, while alleles at HmYb control the yellow hindwing bar. Across HmYb two regions, separated by approximately 100 kb, show significant genotype-by-phenotype associations that are replicated across independent hybrid zones. In contrast, at HmB a single peak of association indicates the likely position of functional sites at three genes, encoding a kinesin, a G-protein coupled receptor, and an mRNA splicing factor. At both HmYb and HmB there is evidence for enhanced linkage disequilibrium (LD) between associated sites separated by up to 14 kb, suggesting that multiple sites are under selection. However, there was no evidence for reduced variation or deviations from neutrality that might indicate a recent selective sweep, consistent with these alleles being relatively old. Of the three genes showing an association with the HmB locus, the kinesin shows differences in wing disc expression between races that are replicated in the co-mimic, Heliconius erato, providing striking evidence for parallel changes in gene expression between Müllerian co-mimics. Wing patterning loci in Heliconius melpomene therefore show a haplotype structure maintained by selection, but no evidence for a recent selective sweep. The complex genetic pattern contrasts with the simple genetic basis of many adaptive traits studied previously, but may provide a better model for most adaptation in natural populations that has arisen over

  11. Thermal balloon ablation versus laparoscopic supracervical hysterectomy for the surgical treatment of heavy menstrual bleeding: a randomized study.

    PubMed

    Sesti, Francesco; Ruggeri, Velia; Pietropolli, Adalgisa; Piancatelli, Raffaella; Piccione, Emilio

    2011-11-01

    To compare postoperative outcomes and effects on quality of life following thermal balloon ablation (TBA) or laparoscopic supracervical hysterectomy (LSH) in women with heavy menstrual bleeding (HMB). Sixty-eight women requiring surgical treatment for HMB were randomly allocated into two treatment arms: TBA (n = 34) and LSH (n = 34). The randomization procedure was based on a computer-generated list. The primary outcome was a comparison of the effects on menstrual bleeding (Pictorial Blood Loss Assessment Chart [PBAC]) between the two procedures. The secondary outcome measures were quality of life, improvement of bleeding patterns, intensity of postoperative pain, and early postoperative complications. Continuous outcome variables were analyzed using Student's t-test. Discrete variables were analyzed with the χ2 test or Fisher's exact test. P < 0.05 was considered statistically significant. The PBAC score was significantly reduced in both treatment groups. After LSH all women had amenorrhea. After TBA there was a significant improvement of bleeding frequency and length. The postoperative pain intensity at 24 h was significantly minor in women treated with TBA rather than with LSH. The Medical Outcomes Survey Short Form 36 (SF-36) score improved in both groups. However, LSH showed a negative impact on the emotional state. No intraoperative complications occurred, and no case was returned to the theatre in either group. The effectiveness of TBA as a possible treatment of HMB is confirmed. However, LSH showed a definitive improvement of the symptoms, and a better life quality profile. Further controlled prospective studies are required for identifying the best surgical approach in women with HMB. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

  12. JPRS Report, East Asia, Southeast Asia.

    DTIC Science & Technology

    1988-04-11

    supported economic and politico -military pro- grams which invariably run counter to the interest of the broad masses. There is a tendency among the... Partido Demokratiko Sosyalista ng Pili- pinas (PDSP) also has ties with the MNLF. How are your relations with this group? [Answer] Negligible. Some...invasion by the Partido Komunista ng Phili- pinas (PKP),—regrouped in 1948 to form the Hukbong Mapagpalaya ng Bayan (HMB) in an attempt to seize

  13. Breast milk donation after neonatal death in Australia: a report.

    PubMed

    Carroll, Katherine E; Lenne, Brydan S; McEgan, Kerri; Opie, Gillian; Amir, Lisa H; Bredemeyer, Sandra; Hartmann, Ben; Jones, Rachel; Koorts, Pieter; McConachy, Helen; Mumford, Patricia; Polverino, Jan

    2014-01-01

    Lactation and breast milk can hold great value and meaning for grieving mothers who have experienced a recent death of an infant. Donation to a human milk bank (HMB) as an alternative to discarding breast milk is one means of respecting the value of breast milk. There is little research, national policy discussion, or organizational representation in Australia on the subject of breast milk donation after infant death. On 29 November 2013 the Mercy Hospital for Women in Melbourne, Australia hosted Australia's first National Stakeholder Meeting (NSM) on the topic of milk donation after neonatal death. The NSM drew together representatives from Australian HMBs, neonatal intensive care units (NICUs) currently using donor human milk, and Australia's chief NICU parent support organization. The NSM was video-recorded and transcribed, and analyzed thematically by researchers. This article reports the seven dominant themes discussed by stakeholders during the NSM: the spectrum of women's lactation and donation experiences after infant death; the roles of the HMB and NICU in meeting the needs of the bereaved donor; how bereaved mothers' lactation autonomy may interface with a HMB's donation guidelines; how milk donation may be discussed with bereaved mothers; the variation between four categories of milk donation after neonatal death; the impact of limited resources and few HMBs on providing donation programs for bereaved mothers in Australia. This article provides evidence from researchers and practitioners that can assist HMB staff in refining their bank's policy on milk donation after infant death, and provides national policy makers with key considerations to support lactation, human milk banking, and bereavement services nation-wide.

  14. Effects of amino acid derivatives on physical, mental, and physiological activities.

    PubMed

    Luckose, Feby; Pandey, Mohan Chandra; Radhakrishna, Kolpe

    2015-01-01

    Nutritional ergogenic aids have been in use for a long time to enhance exercise and sports performance. Dietary components that exhibit ergogenic activity are numerous and their consumption is common and popular among athletes. They often come under scrutiny by legal authorities for their claimed benefits and safety concerns. Amino acid derivatives are propagated as being effective aids to enhance physical and mental performance in many ways, even though studies have pointed out that individuals who are deficient are more likely to benefit from dietary supplementation of amino acid derivatives than normal humans. In this review, some of the most common and widely used amino acids derivatives in sports and athletics namely creatine, tyrosine, carnitine, HMB, and taurine have been discussed for their effects on exercise performance, mental activity as well as body strength and composition. Creatine, carnitine, HMB, and taurine are reported to delay the onset of fatigue, improve exercise performance, and body strength. HMB helps in increasing fat-free mass and reduce exercise induced muscle injury. Taurine has been found to reduce oxidative stress during exercise and also act as an antihypertensive agent. Although, studies have not been able to find any favorable effect of tyrosine administration on exercise performance, it has been proved to be very effective in fighting stress, improving mood and cognitive performance particularly in sleep-deprived subjects. While available data from published studies and findings are equivocal about the efficacy of creatine, tyrosine, and HMB, more comprehensive researches on carnitine and taurine are necessary to provide evidence for the theoretical basis of their ergogenic role in nutritional modification and supplementation.

  15. P3 and P4 position analysis of vinyl ester pseudopeptide proteasome inhibitors.

    PubMed

    Marastoni, Mauro; Baldisserotto, Anna; Trapella, Claudio; Gavioli, Riccardo; Tomatis, Roberto

    2006-06-15

    Two small libraries of tripeptidic-based vinyl ester derivative proteasome inhibitors were synthesized and tested, starting with the Hmb-Val-Gln-Leu-VE prototype. The P3 and P4 positions were investigated with a complete set of amino acid residues, some of which showed remarkable selective inhibition of the trypsin-like (beta2) subunit. In both positions, aromatic and hydrophobic residues were preferred.

  16. Endometrial haemostasis and menstruation.

    PubMed

    Davies, Joanna; Kadir, Rezan A

    2012-12-01

    Under normal physiological circumstances menstruation is a highly regulated, complex process that is under strict hormonal control. During normal menstruation, progesterone withdrawal initiates menstruation. The cessation of menstrual bleeding is achieved by endometrial haemostasis via platelet aggregation, fibrin deposition and thrombus formation. Local endocrine, immunological and haemostatic factors interact at a molecular level to control endometrial haemostasis. Tissue factor and thrombin play a key role locally in the cessation of menstrual bleeding through instigation of the coagulation factors. On the other hand, fibrinolysis prevents clot organisation within the uterine cavity while plasminogen activator inhibitors (PAI) and thrombin-activatable fibrinolysis inhibitors control plasminogen activators and plasmin activity. Abnormalities of uterine bleeding can result from imbalance of the haemostatic factors. The most common abnormality of uterine bleeding is heavy menstrual bleeding (HMB). Modern research has shown that an undiagnosed bleeding disorder, in particular von Willebrand disease (VWD) and platelet function disorders, can be an underlying cause of HMB. This has led to a change in the approach to the management of HMB. While full haemostatic assessment is not required for all women presenting with HMB, menstrual score and bleeding score can help to discriminate women who are more likely to have a bleeding disorder and benefit from laboratory haemostatic evaluation. Haemostatic agents (tranexamic acid and DDAVP) enhance systemic and endometrial haemostasis and are effective in reducing menstrual blood loss in women with or without bleeding disorders. Further research is required to enhance our understanding of the complex interactions of haemostatic factors in general, and specifically within the endometrium. This will lead to the development of more targeted interventions for the management of abnormal uterine bleeding in the future.

  17. [Histological findings in an irradiated choroidal melanoma].

    PubMed

    Koinzer, S; Hasselbach, H; Bräsen, J H; Leuschner, I; Roider, J

    2011-06-01

    Histological findings of choroidal melanomas after proton beam irradiation have been reported for complicated cases after enucleation. We present specimens of a tumor after transretinal probe excision. One year after irradiation, the biopsy was examined histologically. The specimens showed pigmented, spindle-shaped cells staining positively for Melan-A and HMB-45. Ki-67 showed low proliferation. Caspase-3 staining was normal. The melanoma still contained vital and even single proliferating cells, but regressed afterwards without additional therapy.

  18. Factors controlling mud accumulation in the Heuksan mud belt off southwestern Korea

    NASA Astrophysics Data System (ADS)

    Chang, Tae Soo; Ha, Hun Jun; Chun, Seung Soo

    2015-12-01

    The Heuksan mud belt (hereafter HMB) is 20~50 km wide, ~200 km long, and ~50 m thick, having accumulated in the course of the Holocene transgression on the tide-dominated epicontinental shelf southwest of Korea. The internal architecture of the HMB is characterized by offshore prograding clinoforms. Of particular interest are the depositional processes responsible for this anomalously thick mud accumulation within a relatively short period of time. Tidal currents are important in the dispersal of mud in the HMB, although these alone cannot explain such an enormous mud deposit. In order to understand the formative processes of the HMB, a detailed sedimentary facies analysis, including high-resolution grain-size measurements, has been conducted on more than 30 short cores and three long drill cores recovered from the mud belt. Five major mud facies were identified. Of these, mud sequences showing a thickening-thinning trend of alternating silt and clay laminae suggestive of a tidal origin occur dominantly at inner to mid shelf locations. By contrast, internally structureless muds with sharp bases and no bioturbation, which are interpreted of representing fluid-mud deposits, are widespread at mid to outer shelf locations. Wave-generated mud ripples and storm beds on the inner shelf suggest that storm waves in winter resuspend previously deposited mud to form near-bed fluid-mud suspensions with resulting gravity-driven mud transport across the low-gradient outer shelf. This previously not recognized process is probably a major factor controlling depositional processes on the giant mud belt, enabling rapid accumulation and offshore progradation even during transgression, i.e., at times of sea-level rise.

  19. Metabolism of 5-methylthioribose to methionine

    SciTech Connect

    Miyazaki, J.H.; Yang, S.F.

    1987-06-01

    During ethylene biosynthesis, the H/sub 3/CS-group of S-adenosylmethionine is released as 5'-methylthioadenosine, which is recycled to methionine via 5-methylthioribose (MTR). In mungbean hypocotyls and cell-free extracts of avocado, (/sup 14/C)MTR was converted into labeled methionine via 2-keto-4-methylthiobutyric acid (KMB) and 2-hydroxy-4-methylthiobutyric acid (HMB), as intermediates. Incubation of (ribose-U-/sup 14/C)MTR with avocado extract resulted in the production of (/sup 14/C)formate, indicating the conversion of MTR to KMB involves a loss of formate, presumably from C-1 of MTR. Tracer studies showed that KMB was converted readily in vivo and in vitro to methionine, while HMB was converted much more slowly. The conversion of KMB to methionine by dialyzed avocado extract requires an amino donor. Among several potential donors examined, L-glutamine was the most efficient. Anaerobiosis inhibited only partially the oxidation of MTR to formate, KMB/HMB, and methionine by avocado extract. The role of O/sub 2/ in the conversion of MTR to methionine is discussed.

  20. Effect of dacarbazine (DTIC) on cultures from malignant melanoma of the choroid: an immunohistochemical and electron microscopic study.

    PubMed

    Sivkova, N; Steuhl, K P; Rohrbach, J; Popova, L

    1999-01-01

    Dacarbazine (DTIC) is a very effective chemotherapeutic agent used in the treatment of cutaneous melanoma; it also could have a potential therapeutic value as an antimetastatic agent in the treatment of choroidal melanoma. To study the HMB-45 and S100 protein expression in choroidal melanoma cultures with and without DTIC, and compare the immunohistochemical and electron microscopic changes in both groups. Five- and seven-day cultures of choroidal melanoma (n = 21) were cultivated in diffusion chambers. The cultures were divided in two groups: I group (control group)--the cells were grown in 199-medium; II group--the cells were in 199-medium supplemented with 0.03 mg/ml of DTIC. Immunohistochemical studies were performed with paraffin-embedded material of the cultures by the avidin-biotin-alkaline phosphatase technique. Araldit-embedded material was studied by electron microscopy. The expression of HMB-45 and S100 protein in the cultures with DTIC ranged from slightly positive to negative. The tumor cells were severely damaged. Electron microscopy in this group showed presence only of cellular fragments. In the DTIC-free group the HMB-45 and S100 expressions were strongly positive. There were no electron microscopic evidence of cellular death. DTIC suppresses the growth of choroidal melanoma in vitro. These results indicate that further studies are warranted to elucidate the effect of DTIC in vivo.

  1. Long-term incidence of hysterectomy following endometrial resection or endometrial ablation for heavy menstrual bleeding.

    PubMed

    Kalampokas, Emmanouil; McRobbie, Sarah; Payne, Fiona; Parkin, David E

    2017-10-01

    To estimate the incidence of hysterectomy following endometrial resection or endometrial ablation (ERA). The present retrospective study enrolled women who underwent ERA for benign heavy menstrual bleeding (HMB) at Aberdeen Royal Infirmary, UK, between February 1, 1990, and December 31, 1997; follow-up data to the end of 2015 were included from the pathology laboratory report system from the single pathology laboratory in the region. Data were compared between patients who did or did not require a hysterectomy after ERA. There were 901 patients who underwent ERA for HMB during the study period. The mean age of patients was 42.3 ± 5.7 years; of the patients included, 206 (22.9%) women underwent hysterectomy and these patients had a mean age of 40.1 years. Of the patients who had hysterectomies, 155 (75.2%) did so in the first 5 years following ERA, 31 (15.0%) did within 6-10 years, 11 (5.3%) did within 11-15 years, and 9 (4.4%) did within 16-20 years. In total, 51 (24.8%) of these patients had hysterectomies within 6-25 years of ERA. A significant majority of women who underwent ERA for HMB did not require hysterectomy up to 25 years after the procedure. © 2017 International Federation of Gynecology and Obstetrics.

  2. Impact of a new levonorgestrel intrauterine system, Levosert(®), on heavy menstrual bleeding: results of a one-year randomised controlled trial.

    PubMed

    Mawet, Marie; Nollevaux, Fabrice; Nizet, Dominique; Wijzen, Fabienne; Gordenne, Valérie; Tasev, Niso; Segedi, Dimitrije; Marinescu, Bogdan; Enache, Andreea; Parhomenko, Vadim; Frankenne, Francis; Foidart, Jean-Michel

    2014-06-01

    To evaluate a new levonorgestrel-releasing intrauterine system (LNG-IUS) called Levosert(®) for the treatment of heavy menstrual bleeding (HMB) in comparison to the reference product Mirena(®). A multicentre, randomised, controlled trial, in non-menopausal women diagnosed with functional HMB (defined as menstrual blood loss [MBL] ≥ 80 mL) randomised to either Levosert(®) or Mirena(®) and followed for up to one year. MBL was evaluated using a validated modified version of the Wyatt pictogram. A total of 280 women were randomised (141 to Levosert(®) and 139 to Mirena(®)). During the one-year treatment period, both Levosert(®) and Mirena(®) dramatically decreased MBL and increased haemoglobin and ferritin levels. There were no statistically significant differences between Levosert(®) and Mirena(®) regarding any of the parameters evaluated during the study. Similar bleeding patterns were observed in both groups. Levosert(®) was inserted with the same ease as Mirena(®). Both treatments were associated with identical expulsion rates and no perforations occurred in either treatment group. Levosert(®), a new LNG-IUS designed to release the same daily amount of LNG as Mirena(®), is highly effective in the treatment of HMB. No differences were observed between Levosert(®) and Mirena(®) regarding all evaluated outcomes, including safety profile.

  3. Rogue waves of the Hirota and the Maxwell-Bloch equations.

    PubMed

    Li, Chuanzhong; He, Jingsong; Porsezian, K; Porseizan, K

    2013-01-01

    In this paper, we derive a Darboux transformation of the Hirota and the Maxwell-Bloch (H-MB) system which is governed by femtosecond pulse propagation through an erbium doped fiber and further generalize it to the matrix form of the n-fold Darboux transformation of this system. This n-fold Darboux transformation implies the determinant representation of nth solutions of (E([n]),p([n]),η([n])) generated from the known solution of (E,p,η). The determinant representation of (E([n]),p([n]),η([n])) provides soliton solutions, positon solutions, and breather solutions (both bright and dark breathers) of the H-MB system. From the breather solutions, we also construct a bright and dark rogue wave solution for the H-MB system, which is currently one of the hottest topics in mathematics and physics. Surprisingly, the rogue wave solution for p and η has two peaks because of the order of the numerator and denominator of them. Meanwhile, after fixing the time and spatial parameters and changing two other unknown parameters α and β, we generate a rogue wave shape.

  4. Primary oral melanoma: A histopathological and immunohistochemical study of 22 cases of Latin America

    PubMed Central

    Toral-Rizo, Víctor H.; León, Jorge E.; Contreras, Elisa; Carlos, Román; Delgado-Azañero, Wilson; Mosqueda-Taylor, Adalberto; de-Almeida, Oslei P.

    2012-01-01

    Objective: The aim of this study was to analyze the histopathological and immunohistochemical characteristics of 22 cases of primary oral melanomas (OM). Study Design: Twenty two cases of primary oral melanoma were analyzed by description of their histopathological features and immunohistochemical study using the antibodies S-100, HMB-45, Melan-A and Ki-67. Results: The mean age was 58 years and 14 cases were female. The main affected sites were the hard palate, followed by the upper gingiva. Microscopically, 15 cases presented level III of invasion, 2 cases were amelanotic and 13 showed a mixed epithelioid and plasmacytoid or spindle cells composition. Some cases showed necrosis, perivascular and perineural invasion. S-100 and HMB-45 were positive in all cases, but 3 cases were negative for Melan-A. The proliferative index with Ki-67 was high, with labeling index ranging from 15.51% to 63% of positive cells. Conclusion: S-100 and HMB-45 are more frequently expressed than Melan-A in primary oral melanomas and these markers are helpful to confirm the diagnosis. Key words:Oral melanoma, histopathology, immunohistochemistry. PMID:22143732

  5. An international response to questions about terminologies, investigation, and management of abnormal uterine bleeding: use of an electronic audience response system.

    PubMed

    Munro, Malcolm G; Broder, Michael; Critchley, Hilary O D; Matteson, Kristen; Haththotuwa, Rohana; Fraser, Ian S

    2011-09-01

    More than 600 registrants attended a two-hour interactive symposium on abnormal uterine bleeding (AUB) at the Federation of Gynecology and Obstetrics World Congress in Cape Town, October 2009. Nearly 250 of these participants answered multiple questions through an electronic audience responder system. The audience heard five structured presentations on clinically important and controversial aspects of AUB, including terminologies and definitions, classification of causes, mechanisms of AUB in the absence of structural lesions of the reproductive tract, the potential for a structured menstrual history, and management of heavy menstrual bleeding (HMB) in low-resource settings. Numerous demographic details were collected, and a total of 30 questions to the audience were interspersed through each of the presentations. The audience demonstrated great variation in the way the terms AUB, menorrhagia, and dysfunctional uterine bleeding (DUB) are used, and considerable majorities agreed that the terms menorrhagia and DUB should be abolished. AUB should be the overarching term to describe all symptomatic departures from normal menstruation or the menstrual cycle. HMB is a suitable replacement term for menorrhagia. DUB can be replaced by the three clinical entities comprising "nonstructural" causes of AUB. There was a high consistency across demographic subgroups in answers to most questions. Acute and chronic AUB were defined, and aspects of a classification system for causes of AUB and of a structured menstrual history were explored. Issues related to investigation and hormonal treatment of HMB in low-resource settings were explored by registrants from developing countries.

  6. Efficacy and Safety of Leucine Supplementation in the Elderly.

    PubMed

    Borack, Michael S; Volpi, Elena

    2016-12-01

    Leucine supplementation has grown in popularity due to the discovery of its anabolic effects on cell signaling and protein synthesis in muscle. The current recommendation is a minimum intake of 55 mg ⋅ kg(-1)(.) d(-1) Leucine acutely stimulates skeletal muscle anabolism and can overcome the anabolic resistance of aging. The value of chronic leucine ingestion for muscle growth is still unclear. Most of the research into leucine consumption has focused on efficacy. To our knowledge, very few studies have sought to determine the maximum safe level of intake. Limited evidence suggests that intakes of ≤1250 mg ⋅ kg(-1)(.) d(-1) do not appear to have any health consequences other than short-term elevated plasma ammonia concentrations. Similarly, no adverse events have been reported for the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), although no studies have tested HMB toxicity in humans. Therefore, future research is needed to evaluate leucine and HMB toxicity in the elderly and in specific health conditions. © 2016 American Society for Nutrition.

  7. Impact of a new levonorgestrel intrauterine system, Levosert®, on heavy menstrual bleeding: results of a one-year randomised controlled trial

    PubMed Central

    Nollevaux, Fabrice; Nizet, Dominique; Wijzen, Fabienne; Gordenne, Valérie; Tasev, Niso; Segedi, Dimitrije; Marinescu, Bogdan; Enache, Andreea; Parhomenko, Vadim; Frankenne, Francis; Foidart, Jean-Michel

    2014-01-01

    Objective To evaluate a new levonorgestrel-releasing intrauterine system (LNG-IUS) called Levosert® for the treatment of heavy menstrual bleeding (HMB) in comparison to the reference product Mirena®. Methods A multicentre, randomised, controlled trial, in non-menopausal women diagnosed with functional HMB (defined as menstrual blood loss [MBL] ≥ 80 mL) randomised to either Levosert® or Mirena® and followed for up to one year. MBL was evaluated using a validated modified version of the Wyatt pictogram. Results A total of 280 women were randomised (141 to Levosert® and 139 to Mirena®). During the one-year treatment period, both Levosert® and Mirena® dramatically decreased MBL and increased haemoglobin and ferritin levels. There were no statistically significant differences between Levosert® and Mirena® regarding any of the parameters evaluated during the study. Similar bleeding patterns were observed in both groups. Levosert® was inserted with the same ease as Mirena®. Both treatments were associated with identical expulsion rates and no perforations occurred in either treatment group. Conclusion Levosert®, a new LNG-IUS designed to release the same daily amount of LNG as Mirena®, is highly effective in the treatment of HMB. No differences were observed between Levosert® and Mirena® regarding all evaluated outcomes, including safety profile. PMID:24666176

  8. Ovalbumin labeling with p-hydroxymercurybenzoate: The effect of different denaturing agents and the kinetics of reaction.

    PubMed

    Campanella, Beatrice; Onor, Massimo; Biancalana, Lorenzo; D'Ulivo, Alessandro; Bramanti, Emilia

    2015-08-15

    The aim of our study was to investigate how denaturing agents commonly used in protein analysis influence the labeling between a reactive molecule and proteins. For this reason, we investigated the labeling of ovalbumin (OVA) as a globular model protein with p-hydroxymercurybenzoate (pHMB) in its native state (phosphate buffer solution) and in different denaturing conditions (8 molL(-1) urea, 3 molL(-1) guanidinium thiocyanate, 6 molL(-1) guanidinium chloride, 0.2% sodium dodecyl sulfate, and 20% methanol). In addition to chemical denaturation, thermal denaturation was also tested. The protein was pre-column simultaneously denatured and derivatized, and the pHMB-labeled denatured OVA complexes were analyzed by size exclusion chromatography (SEC) coupled online with chemical vapor generation-atomic fluorescence spectrometry (CVG-AFS). The number of -SH groups titrated greatly depends on the protein structure in solution. Indeed, we found that, depending on the adopted denaturing conditions, OVA gave different aggregate species that influence the complexation process. The results were compared with those obtained by a common alternative procedure for the titration of -SH groups that employs monobromobimane (mBBr) as tagging molecule and molecular fluorescence spectroscopy as detection technique. We also investigated the labeling kinetics for denatured OVA and pHMB, finding that the 4 thiolic groups of OVA have a very different reactivity toward mercury labeling, in agreement with previous studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Genetic transformation of Knufia petricola A95 - a model organism for biofilm-material interactions

    PubMed Central

    2014-01-01

    We established a protoplast-based system to transfer DNA to Knufia petricola strain A95, a melanised rock-inhabiting microcolonial fungus that is also a component of a model sub-aerial biofilm (SAB) system. To test whether the desiccation resistant, highly melanised cell walls would hinder protoplast formation, we treated a melanin-minus mutant of A95 as well as the type-strain with a variety of cell-degrading enzymes. Of the different enzymes tested, lysing enzymes from Trichoderma harzianum were most effective in producing protoplasts. This mixture was equally effective on the melanin-minus mutant and the type-strain. Protoplasts produced using lysing enzymes were mixed with polyethyleneglycol (PEG) and plasmid pCB1004 which contains the hygromycin B (HmB) phosphotransferase (hph) gene under the control of the Aspergillus nidulans trpC. Integration and expression of hph into the A95 genome conferred hygromycin resistance upon the transformants. Two weeks after plating out on selective agar containing HmB, the protoplasts developed cell-walls and formed colonies. Transformation frequencies were in the range 36 to 87 transformants per 10 μg of vector DNA and 106 protoplasts. Stability of transformation was confirmed by sub-culturing the putative transformants on selective agar containing HmB as well as by PCR-detection of the hph gene in the colonies. The hph gene was stably integrated as shown by five subsequent passages with and without selection pressure. PMID:25401079

  10. Mosquito salivary gland extracts induce EBV-infected NK cell oncogenesis via CD4 T cells in patients with hypersensitivity to mosquito bites.

    PubMed

    Asada, Hideo; Saito-Katsuragi, Mamiko; Niizeki, Hironori; Yoshioka, Akira; Suguri, Setsuo; Isonokami, Masaaki; Aoki, Toshiyuki; Ishihara, Shigehiko; Tokura, Yoshiki; Iwatsuki, Keiji; Miyagawa, Sachiko

    2005-11-01

    Severe hypersensitivity to mosquito bites (HMB) is characterized by intense local skin reactions and systemic symptoms such as high fever, lymphadenopathy, and hepatosplenomegaly. Patients with HMB often have natural killer (NK) cell lymphocytosis associated with Epstein-Barr virus (EBV) infection. Here we investigated whether mosquito bites have any influence on the oncogenesis of EBV-infected NK cells. We examined six HMB patients with EBV-infected NK cell lymphocytosis. We first demonstrated that CD4+ T cells, but not NK cells, proliferated well in response to mosquito salivary gland extracts (SGE), especially to SGE of Aedes albopictus. When NK cells were cocultured with autologous CD4+ T cells stimulated by mosquito SGE, the expression of viral oncogene latent membrane protein 1 (LMP1) was remarkably enhanced. Next, we stimulated mononuclear cells of the patients with mosquito SGE, and NK cell counts were monitored for 28 d. The counts changed little from initial levels in the culture with mosquito SGE, whereas they decreased steadily in the culture without the extracts. Furthermore, we detected LMP1 mRNA in the skin lesion induced by mosquito SGE. These results suggest that mosquito bites can induce expression of the viral oncogene LMP1 in NK cells via mosquito antigen-specific CD4+ T cells, which is involved in the oncogenesis of NK cells in vivo.

  11. β-Hydroxy-β-methylbutyrate, mitochondrial biogenesis, and skeletal muscle health.

    PubMed

    He, Xi; Duan, Yehui; Yao, Kang; Li, Fengna; Hou, Yongqing; Wu, Guoyao; Yin, Yulong

    2016-03-01

    The metabolic roles of mitochondria go far beyond serving exclusively as the major producer of ATP in tissues and cells. Evidence has shown that mitochondria may function as a key regulator of skeletal muscle fiber types and overall well-being. Maintaining skeletal muscle mitochondrial content and function is important for sustaining health throughout the lifespan. Of great importance, β-hydroxy-β-methylbutyrate (HMB, a metabolite of L-leucine) has been proposed to enhance the protein deposition and efficiency of mitochondrial biogenesis in skeletal muscle, as well as muscle strength in both exercise and clinical settings. Specifically, dietary supplementation with HMB increases the gene expression of peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α), which represents an upstream inducer of genes of mitochondrial metabolism, coordinates the expression of both nuclear- and mitochondrion-encoded genes in mitochondrial biogenesis. Additionally, PGC-1α plays a key role in the transformation of skeletal muscle fiber type, leading to a shift toward type I muscle fibers that are rich in mitochondria and have a high capacity for oxidative metabolism. As a nitrogen-free metabolite, HMB holds great promise to improve skeletal muscle mass and function, as well as whole-body health and well-being of animals and humans.

  12. Effects of beta-hydroxy-beta-methylbutyrate supplementation during resistance training on strength, body composition, and muscle damage in trained and untrained young men: a meta-analysis.

    PubMed

    Rowlands, David S; Thomson, Jasmine S

    2009-05-01

    Beta-hydroxy-beta-methylbutyrate (HMB) is a popular supplement in the resistance training community, with its use supported by claims of increased strength, muscle growth, and improved recovery; however, research outcomes are variable. Therefore, we meta-analyzed the effectiveness of HMB on strength, body composition, and muscle damage. Nine qualifying studies yielded 14 comparisons subcategorized by training experience (trained, untrained) to provide 12-13 estimates of strength (upper body, lower body, overall average), 13 estimates of fat and fat-free mass, and 7 estimates of the muscle-damage marker creatine kinase. The meta-analysis comprised 394 subjects (age 23 +/- 2 years, mean +/- between-study SD) with 5 +/- 2 weeks' intervention and 5 +/- 6 h.wk of training. The estimates were analyzed using a meta-analytic mixed model with study sample size as the weighting factor that included the main-effect covariates to control for between-study differences in HMB dose, intervention duration, training load, and dietary cointervention. To interpret magnitudes, meta-analyzed effects were standardized using the composite baseline between-subject SD and were qualified using modified Cohen effect size thresholds. There were small benefits to lower-body (mean +/- 90% confidence limit: 9.9% +/- 5.9%) and average strength (6.6 +/- 5.7%), but only negligible gains for upper-body strength (2.1 +/- 5.5%) were observed in untrained lifters. In trained lifters, all strength outcomes were trivial. Combined (all studies), the overall average strength increase was trivial (3.7 +/- 2.4%), although uncertainty allows for a small benefit. Effects on fat and fat-free mass were trivial, and results regarding creatine kinase were unclear. Supplementation with HMB during resistance training incurs small but clear overall and leg strength gains in previously untrained men, but effects in trained lifters are trivial. The HMB effect on body composition is inconsequential. An explanation for

  13. [Sarcopenia intervention with progressive resistance training and protein nutritional supplements].

    PubMed

    Palop Montoro, M Victoria; Párraga Montilla, Juan Antonio; Lozano Aguilera, Emilio; Arteaga Checa, Milagros

    2015-04-01

    Introducción: El envejecimiento viene acompañado de cambios en la composición corporal entre los que se encuentra una reducción progresiva de la masa muscular, que puede contribuir al desarrollo de limitaciones funcionales en las personas mayores, y donde el estilo de vida juega un papel de especial relevancia. Objetivos: Comprobar la efectividad del entrenamiento de resistencia progresiva, los suplementos nutricionales proteicos y ambas intervenciones combinadas en el tratamiento de la sarcopenia. Método: Revisión de la literatura en las bases de datos Medline, ScienceDirect, CINAHL, ISI WOK y PEDro, mediante la combinación de los descriptores del Medical Subjects Headings (MeSH) referentes a sarcopenia, entrenamiento de fuerza progresiva, suplementos proteicos y personas mayores. Resultados: Un total de 147 estudios fueron encontrados los cuales realizaban ejercicio de resistencia, mediante sesiones de 45-60 minutos, 2-3 veces por semana, y 3-4 series de 8 repeticiones, a una intensidad creciente. Este ejercicio produjo un aumento de la masa muscular y la fuerza, así como incremento en la síntesis de proteínas musculoesqueléticas y tamaño de la fibra muscular. Los suplementos nutricionales tales como el beta-hidroxi-beta-metilbutirato, la leucina y los aminoácidos esenciales produjeron beneficios en la masa muscular. Todos los suplementos aumentaron la fuerza, especialmente cuando se combinaron con el ejercicio de resistencia. Conclusión: La combinación del entrenamiento de resistencia progresiva y las proteínas incluidas en la dieta, o bien en forma de suplementos nutricionales, refuerza los efectos que cada una de estas intervenciones puede tener en el tratamiento de la sarcopenia en las personas mayores.

  14. Is duration of postoperative fasting associated with infection and prolonged length of stay in surgical patients?

    PubMed

    de Assis, Michelli Cristina Silva; Silveira, Carla Rosane de Moraes; Beghetto, Mariur Gomes; de Mello, Daniel Elza

    2014-10-01

    Objetivo: Constatar si el periodo de ayuno postoperatorio aumenta el riesgo de infeccion y prolonga la estancia hospitalaria. Métodos: Estudio de cohorte prospectivo. Fueron incluidos pacientes en cirugia selectiva. Se excluyeron aquellos sin posibilidades de evaluacion nutricional, ingresados a unidades de cuidado minimo y con.

  15. Cost-effectiveness of diagnostic strategies for the management of abnormal uterine bleeding (heavy menstrual bleeding and post-menopausal bleeding): a decision analysis.

    PubMed

    Cooper, Natalie A M; Barton, Pelham M; Breijer, Maria; Caffrey, Orla; Opmeer, Brent C; Timmermans, Anne; Mol, Ben W J; Khan, Khalid S; Clark, T Justin

    2014-04-01

    Heavy menstrual bleeding (HMB) and post-menopausal bleeding (PMB) together constitute the commonest gynaecological presentation in secondary care and impose substantial demands on health service resources. Accurate diagnosis is of key importance to realising effective treatment, reducing morbidity and, in the case of PMB, reducing mortality. There are many tests available, including transvaginal scan (TVS), endometrial biopsy (EBx), saline infusion sonography and outpatient hysteroscopy (OPH); however, optimal diagnostic work-up is unclear. To determine the most cost-effective diagnostic testing strategy for the diagnosis and treatment of (i) HMB and (ii) PMB. Parameter inputs were derived from systematic quantitative reviews, individual patient data (IPD) from existing data sets and focused searches for specific data. In the absence of data estimates, the consensus view of an expert clinical panel was obtained. Two clinically informed decision-analytic models were constructed to reflect current service provision for the diagnostic work-up of women presenting with HMB and PMB. The model-based economic evaluation took the form of a cost-effectiveness analysis from the perspective of the NHS in a contemporary, 'one-stop' secondary care clinical setting, where all indicated testing modalities would be available during a single visit. Two potentially cost-effective testing strategies for the initial investigation of women with HMB were identified: OPH alone or in combination with EBx. Although a combination testing strategy of OPH + EBx was marginally more effective, the incremental cost-effectiveness ratio (ICER) was approximately £21,000 to gain one more satisfied patient, whereas for OPH it was just £360 when compared with treatment with the levonorgestrel intrauterine system (LNG-IUS) without investigation. Initial testing with OPH was the most cost-effective testing approach for women wishing to preserve fertility and for women with symptoms refractory to

  16. Hydroxymethylbilane synthase: Complete genomic sequence and amplifiable polymorphisms in the human gene

    SciTech Connect

    Yoo, Hanwook; Warner, C.A.; Chen, Chiahsiang; Desnick, R.J. )

    1993-01-01

    Acute intermittent porphyria (AIP), an autosomal dominant inborn error of heme biosynthesis, results from the half-normal activity of the heme biosynthetic enzyme hydroxymethylbilane synthase (HMB-synthase). Heterozygous individuals are prone to life-threatening acute neurologic attacks, which are precipitated by certain drugs and other metabolic, hormonal, and nutritional factors. Since the biochemical diagnosis of heterozygous individuals has been problematic, recent efforts have focused on the identification of mutations and diagnostically useful restriction fragment length polymorphisms (RFLPS) in the HMB-synthase gene. To facilitate these endeavors, the human HMB-synthase gene, including 1.1 kb of the 5[prime] flanking region, was isolated and completely sequenced in both orientations. The 10,024-bp gene contained 15 exons ranging in size from 39 to 438 bp and 14 introns ranging from 87 to 2913 bp. All intron/exon boundaries conformed to the GT/AG consensus rule. There were six Alu repetitive elements, one of the J and five of the Sa subfamilies. Analysis of the 1. I -kb 5[prime]flanking region revealed putative regulatory elements for the housekeeping promoter including AP1, AP4, SP1, TRE, ENH, and CAC. This region contained 10 HpaII sites and had an overall GC content of 54%. Three new polymorphic sites were identified by the single-strand conformation polymorphism (SSCP) technique, a common BsmAI site in intron 3 (3581 A/G), a common HinfI RFLP in intron 10 (7064 C/A), and a rare MnlI site in intron 14 (7998G/A). The allele frequencies of five previously known and the new polymorphic sites in a normal Caucasian population indicated that the intron 1 and intron 3 RFLPs were in linkage disequilibrium; however, the Hint I site segregated independently. 54 refs., 6 figs., 3 tabs.

  17. Immunohistochemical study of melanocyte-melanocyte stem cell lineage in vitiligo; a clue to interfollicular melanocyte stem cell reservoir.

    PubMed

    Seleit, Iman; Bakry, Ola Ahmed; Abdou, Asmaa Gaber; Dawoud, Noha Mohammed

    2014-05-01

    There has been a long lasting controversy over whether melanocytes (MCs) in vitiligo are actually lost or still present but functionally inactive. We aimed to evaluate the MC cell lineage in follicular and interfollicular vitiliginous epidermis through immunohistochemical localization of Human Melanoma Black-45 (HMB-45) and Tyrosinase Related Protein 2 (TRP2) and to correlate it with clinicopathologic parameters. Using immunohistochemical techniques, skin biopsies from 50 vitiligo patients and 20 age- and gender-matched healthy subjects were examined. Differentiated active MCs were detected in 44% of interfollicular epidermis (IFE) and 46.7% of follicular epidermis (FE) in lesional skin. Melanocyte precursors/stem cells were detected in 54% of IFE and 63.3% of FE in lesional skin. Melanocyte precursors/stem cells of IFE were significantly associated with residual melanin pigment (p = 0.007) and with absence of angiogenesis (p = 0.05). HMB-45 percentage of expression in IFE was positively correlated with MC precursors/stem cells percentage in FE (r = +0.65, p < 0.001) and IFE (r = +0.33, p = 0.01). Melanocyte precursors/stem cells positivity (p < 0.001) was progressively decreasing with advanced histopathologic grading. There was no significant association between interfollicular or follicular expression of HMB-45, TRP2 or MC precursors/stem cells and the clinical type of vitiligo or its duration. In conclusion, functioning MCs may exist in vitiligo. The presence of MC precursors/stem cells in IFE may provide an additional reservoir needed for repigmentation.

  18. Donor human milk for preterm infants: current evidence and research directions.

    PubMed

    Arslanoglu, Sertac; Corpeleijn, Willemijn; Moro, Guido; Braegger, Christian; Campoy, Cristina; Colomb, Virginie; Decsi, Tamas; Domellöf, Magnus; Fewtrell, Mary; Hojsak, Iva; Mihatsch, Walter; Mølgaard, Christian; Shamir, Raanan; Turck, Dominique; van Goudoever, Johannes

    2013-10-01

    The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding tolerance and with reduced cardiovascular risk factors during adolescence. Presence of a human milk bank (HMB) does not decrease breast-feeding rates at discharge, but decreases the use of formula during the first weeks of life. This commentary emphasizes that fresh own mother's milk (OMM) is the first choice in preterm infant feeding and strong efforts should be made to promote lactation. When OMM is not available, DHM is the recommended alternative. When neither OMM nor DHM is available, preterm formula should be used. DHM should be provided from an established HMB, which follows specific safety guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research should focus on the improvement of milk processing in HMB, particularly of heat treatment; on the optimization of HM fortification; and on further evaluation of the potential clinical benefits of processed and fortified DHM.

  19. Distribution and diversity of the haemoglobin-haptoglobin iron-acquisition systems in pathogenic and non-pathogenic Neisseria.

    PubMed

    Harrison, Odile B; Bennett, Julia S; Derrick, Jeremy P; Maiden, Martin C J; Bayliss, Christopher D

    2013-09-01

    A new generation of vaccines containing multiple protein components that aim to provide broad protection against serogroup B meningococci has been developed. One candidate, 4CMenB (4 Component MenB), has been approved by the European Medicines Agency, but is predicted to provide at most 70-80 % strain coverage; hence there is a need for second-generation vaccines that achieve higher levels of coverage. Prior knowledge of the diversity of potential protein vaccine components is a key step in vaccine design. A number of iron import systems have been targeted in meningococcal vaccine development, including the HmbR and HpuAB outer-membrane proteins, which mediate the utilization of haemoglobin or haemoglobin-haptoglobin complexes as iron sources. While the genetic diversity of HmbR has been described, little is known of the diversity of HpuAB. Using whole genome sequences deposited in a Bacterial Isolate Genome Sequence Database (BIGSDB), the prevalence and diversity of HpuAB among Neisseria were investigated. HpuAB was widely present in a range of Neisseria species whereas HmbR was mainly limited to the pathogenic species Neisseria meningitidis and Neisseria gonorrhoeae. Patterns of sequence variation in sequences from HpuAB proteins were suggestive of recombination and diversifying selection consistent with strong immune selection. HpuAB was subject to repeat-mediated phase variation in pathogenic Neisseria and the closely related non-pathogenic Neisseria species Neisseria lactamica and Neisseria polysaccharea but not in the majority of other commensal Neisseria species. These findings are consistent with HpuAB being subject to frequent genetic transfer potentially limiting the efficacy of this receptor as a vaccine candidate.

  20. Liver Transplantation for Acute Intermittent Porphyria: Biochemical and Pathologic Studies of the Explanted Liver

    PubMed Central

    Yasuda, Makiko; Erwin, Angelika L; Liu, Lawrence U; Balwani, Manisha; Chen, Brenden; Kadirvel, Senkottuvelan; Gan, Lin; Fiel, M Isabel; Gordon, Ronald E; Yu, Chunli; Clavero, Sonia; Arvelakis, Antonios; Naik, Hetanshi; Martin, L David; Phillips, John D; Anderson, Karl E; Sadagoparamanujam, Vaithamanithi M; Florman, Sander S; Desnick, Robert J

    2015-01-01

    Acute intermittent porphyria (AIP) is an autosomal-dominant hepatic disorder caused by the half-normal activity of hydroxymethylbilane (HMB) synthase. Symptomatic individuals experience life-threatening acute neurovisceral attacks that are precipitated by factors that induce the hepatic expression of 5-aminolevulinic acid synthase 1 (ALAS1), resulting in the marked accumulation of the putative neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). Here, we provide the first detailed description of the biochemical and pathologic alterations in the explanted liver of an AIP patient who underwent orthotopic liver transplantation (OLT) due to untreatable and debilitating chronic attacks. After OLT, the recipient’s plasma and urinary ALA and PBG rapidly normalized, and her attacks immediately stopped. In the explanted liver, (a) ALAS1 mRNA and activity were elevated approximately ~3- and 5-fold, and ALA and PBG concentrations were increased ~3- and 1,760-fold, respectively; (b) uroporphyrin III concentration was elevated; (c) microsomal heme content was sufficient, and representative cytochrome P450 activities were essentially normal; (d) HMB synthase activity was approximately half-normal (~42%); (e) iron concentration was slightly elevated; and (f) heme oxygenase I mRNA was increased approximately three-fold. Notable pathologic findings included nodular regenerative hyperplasia, previously not reported in AIP livers, and minimal iron deposition, despite the large number of hemin infusions received before OLT. These findings suggest that the neurovisceral symptoms of AIP are not associated with generalized hepatic heme deficiency and support the neurotoxicity of ALA and/or PBG. Additionally, they indicate that substrate inhibition of hepatic HMB synthase activity by PBG is not a pathogenic mechanism in acute attacks. PMID:26062020

  1. Submucosal fibroids and the relation to heavy menstrual bleeding and anemia

    PubMed Central

    PURI, Kanchan; FAMUYIDE, Abimbola O.; ERWIN, Patricia J.; STEWART, Elizabeth A.; LAUGHLIN-TOMMASO, Shannon K.

    2014-01-01

    Objectives To determine the contribution of submucosal fibroids to heavy menstrual bleeding (HMB) and anemia among women with HMB. Study Design Our retrospective study included premenopausal women, who presented to a tertiary care center for HMB between January, 2007 and October, 2011. All women in this cohort underwent flexible office hysteroscopy (n=1,665) and 259 (15.6%) had submucosal fibroids. We also reviewed clinical ultrasounds (n=914) from these women to determine if submucosal fibroids (n=148) or any fibroids (n=434) were present in the uterus. Clinical evaluation of bleeding included hemoglobin and pictorial blood loss assessment charts (PBLAC). Results In our cohort, hysteroscopically-diagnosed submucosal fibroids were associated with significantly lower hemoglobin (adjusted difference −0.35 g/dL (95% confidence interval (CI) −0.56 g/dL, −0.13g/dL) and higher risk of anemia (odds ratio (OR) 1.46, 95% CI 1.04, 2.03). Women with ultrasound-diagnosed submucosal fibroids had lower hemoglobin and anemia, but results were not significant once adjusted for confounders (hemoglobin: adjusted difference −0.21 g/dL, 95%CI −0.47g/dL, 0.06g/dL and anemia: OR 1.28, 95% CI 0.82, 1.97). Ultrasound-diagnosed fibroids anywhere in the uterus were not associated with hemoglobin (p=0.7) or anemia (p=0.8). Self-reported PBLAC scores did not differ between women with and without fibroids diagnosed by either hysteroscopy or ultrasound (p=0.4 & 0.9 respectively). Conclusion Submucosal fibroids were related to lower hemoglobin and higher risk of anemia, but not self-reported bleeding scores. Diagnostic modality was important: hysteroscopically-diagnosed submucosal fibroids had lower hemoglobin and more anemia than ultrasound-diagnosed submucosal fibroids. This may explain inconsistent results in the literature. PMID:24080304

  2. The effect of several organic acids on phytate phosphorus hydrolysis in broiler chicks.

    PubMed

    Liem, A; Pesti, G M; Edwards, H M

    2008-04-01

    Supplementation of some organic acids to a P-deficient diet has been shown to improve phytate P utilization. Two experiments were conducted from 0 to 16 d in battery brooders to determine the effect of various organic acids supplementation on phytate P utilization. In both experiments, birds were fed P-deficient corn and soybean meal-based diets. In experiment 1, citric acid, malic acid, fumaric acid, and EDTA were supplemented. Experiment 2 had a 2 x 2 factorial design with 2 sources of Met, 2-hydroxy-4-(methylthio) butanoic acid (HMB) and dl-Met, with or without 500 U/kg of phytase. In experiment 1, the addition of citric, malic, and fumaric acids increased percentage of bone ash, but only the effect of citric acid was significant. The addition of citric and malic acids also significantly increased the retention of P and phytate P (P<0.05). In experiment 2, the addition of phytase to the diet significantly increased 16-d BW gain, feed intake, percentage of bone ash, milligrams of bone ash, phytate P disappearance, and decreased the incidence of P-deficiency rickets. Methionine source did not affect 16-d BW gain, feed intake, feed efficiency, milligrams of bone ash, or P rickets incidence. However, the birds fed HMB had a higher percentage of bone ash and phytate P disappearance compared with the groups fed dl-Met only when phytase was added to the diets. The additions of citric acid and HMB improved phytate P utilization. However, the reason why some organic acids are effective whereas others are not is not apparent.

  3. Parameter estimation and actuator characteristics of hybrid magnetic bearings for axial flow blood pump applications.

    PubMed

    Lim, Tau Meng; Cheng, Shanbao; Chua, Leok Poh

    2009-07-01

    Axial flow blood pumps are generally smaller as compared to centrifugal pumps. This is very beneficial because they can provide better anatomical fit in the chest cavity, as well as lower the risk of infection. This article discusses the design, levitated responses, and parameter estimation of the dynamic characteristics of a compact hybrid magnetic bearing (HMB) system for axial flow blood pump applications. The rotor/impeller of the pump is driven by a three-phase permanent magnet brushless and sensorless motor. It is levitated by two HMBs at both ends in five degree of freedom with proportional-integral-derivative controllers, among which four radial directions are actively controlled and one axial direction is passively controlled. The frequency domain parameter estimation technique with statistical analysis is adopted to validate the stiffness and damping coefficients of the HMB system. A specially designed test rig facilitated the estimation of the bearing's coefficients in air-in both the radial and axial directions. Experimental estimation showed that the dynamic characteristics of the HMB system are dominated by the frequency-dependent stiffness coefficients. By injecting a multifrequency excitation force signal onto the rotor through the HMBs, it is noticed in the experimental results the maximum displacement linear operating range is 20% of the static eccentricity with respect to the rotor and stator gap clearance. The actuator gain was also successfully calibrated and may potentially extend the parameter estimation technique developed in the study of identification and monitoring of the pump's dynamic properties under normal operating conditions with fluid.

  4. Non-contraceptive benefits of hormonal and intrauterine reversible contraceptive methods.

    PubMed

    Bahamondes, Luis; Valeria Bahamondes, M; Shulman, Lee P

    2015-01-01

    Most contraceptive methods present benefits beyond contraception; however, despite a large body of evidence, many healthcare professionals (HCPs), users and potential users are unaware of those benefits. This review evaluates the evidence for non-contraceptive benefits of hormonal and non-hormonal contraceptive methods. We searched the medical publications in PubMed, POPLINE, CENTRAL, EMBASE and LILACS for relevant articles, on non-contraceptive benefits of the use of hormonal and intrauterine reversible contraceptive methods, which were published in English between 1980 and July 2014. Articles were identified using the following search terms: 'contraceptive methods', 'benefits', 'cancer', 'anaemia', 'heavy menstrual bleeding (HMB)', 'endometrial hyperplasia', 'endometriosis' and 'leiomyoma'. We identified, through the literature search, evidence that some combined oral contraceptives have benefits in controlling HMB and anaemia, reducing the rate of endometrial, ovarian and colorectal cancer and ectopic pregnancy as well as alleviating symptoms of premenstrual dysphoric disorder. Furthermore, the use of the levonorgestrel-releasing intrauterine system also controls HMB and anaemia and endometrial hyperplasia and cancer, reduces rates of endometrial polyps in users of tamoxifen and alleviates pain associated with endometriosis and adenomyosis. Depot medroxyprogesterone acetate controls crises of pain associated with sickle cell disease and endometriosis. Users of the etonogestrel-releasing contraceptive implant have the benefits of a reduction of pain associated with endometriosis, and users of the copper intrauterine device have reduced rates of endometrial and cervical cancer. Despite the high contraceptive effectiveness of many hormonal and intrauterine reversible contraceptive methods, many HCPs, users and potential users are concerned mainly about side effects and safety of both hormonal and non-hormonal contraceptive methods, and there is scarce information

  5. Steroids Regulate CXCL4 in the Human Endometrium During Menstruation to Enable Efficient Endometrial Repair.

    PubMed

    Maybin, Jacqueline A; Thiruchelvam, Uma; Madhra, Mayank; Saunders, Philippa T K; Critchley, Hilary O D

    2017-06-01

    Repair of the endometrial surface at menstruation must be efficient to minimize blood loss and optimize reproductive function. The mechanism and regulation of endometrial repair remain undefined. To determine the presence/regulation of CXCL4 in the human endometrium as a putative repair factor at menses. Endometrial tissue was collected throughout the menstrual cycle from healthy women attending the gynecology department. Menstrual blood loss was objectively measured in a subset, and heavy menstrual bleeding (HMB) was defined as >80 mL per cycle. Monocytes were isolated from peripheral blood. CXCL4 messenger RNA (mRNA) and protein were identified by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The function/regulation of endometrial CXCL4 was explored by in vitro cell culture. CXCL4 mRNA concentrations were significantly increased during menstruation. Intense staining for CXCL4 was detected in late secretory and menstrual tissue, localized to stromal, epithelial and endothelial cells. Colocalization identified positive staining in CD68+ macrophages. Treatment of human endometrial stromal and endothelial cells (hESCs and HEECs, respectively) with steroids revealed differential regulation of CXCL4. Progesterone withdrawal resulted in significant increases in CXCL4 mRNA and protein in hESCs, whereas cortisol significantly increased CXCL4 in HEECs. In women with HMB, CXCL4 was reduced in endothelial cells during the menstrual phase compared with women with normal menstrual bleeding. Cortisol-exposed macrophages displayed increased chemotaxis toward CXCL4 compared with macrophages incubated with estrogen or progesterone. These data implicate CXCL4 in endometrial repair after menses. Reduced cortisol at the time of menses may contribute to delayed endometrial repair and HMB, in part by mechanisms involving aberrant expression of CXCL4.

  6. Effects of six-month supplementation with beta-hydroxy-beta-methylbutyrate, glutamine, and arginine on vascular endothelial function of older adults

    PubMed Central

    Ellis, Amy; Patterson, Morgan; Dudenbostel, Tanja; Calhoun, David; Gower, Barbara

    2015-01-01

    Background Vascular endothelial function declines with advancing age, due in part to increased oxidative stress and inflammation, and this age-related vascular dysfunction has been identified as an independent risk factor for cardiovascular diseases (CVD). This double-blind, placebo-controlled trial investigated the effects of a dietary supplement containing β-hydroxy-β-methylbutyrate (HMB), glutamine, and arginine on endothelial-dependent vasodilation of older adults. Subjects/Methods Thirty-one community-dwelling men and women aged 65-87 years were randomly assigned to two groups. The treatment group received two doses of the supplement daily (totaling 3g HMB, 14g glutamine, 14g arginine) for six months while the control group received an isocaloric placebo. At baseline and week 24, vascular endothelial function was measured by flow-mediated dilation of the brachial artery, and fasting blood samples were obtained to measure high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α). Results Paired samples t-tests revealed a 27% increase in flow-mediated dilation among the treatment group (p=0.003) while no change was observed in the placebo group (p=0.651). Repeated-measures ANOVA verified a significant time by group interaction (p=0.038). Although no significant changes were observed for hsCRP or TNF-α, a trend was observed for increasing hsCRP among the placebo group only (p=0.059). Conclusions These results suggest that dietary supplementation of HMB, glutamine, and arginine may favorably impact vascular endothelial function in older adults. Additional studies are needed to elucidate whether reduced inflammation or other mechanisms may underlie the benefits of supplementation. PMID:26306566

  7. Distribution and diversity of the haemoglobin–haptoglobin iron-acquisition systems in pathogenic and non-pathogenic Neisseria

    PubMed Central

    Harrison, Odile B.; Bennett, Julia S.; Derrick, Jeremy P.; Bayliss, Christopher D.

    2013-01-01

    A new generation of vaccines containing multiple protein components that aim to provide broad protection against serogroup B meningococci has been developed. One candidate, 4CMenB (4 Component MenB), has been approved by the European Medicines Agency, but is predicted to provide at most 70–80 % strain coverage; hence there is a need for second-generation vaccines that achieve higher levels of coverage. Prior knowledge of the diversity of potential protein vaccine components is a key step in vaccine design. A number of iron import systems have been targeted in meningococcal vaccine development, including the HmbR and HpuAB outer-membrane proteins, which mediate the utilization of haemoglobin or haemoglobin–haptoglobin complexes as iron sources. While the genetic diversity of HmbR has been described, little is known of the diversity of HpuAB. Using whole genome sequences deposited in a Bacterial Isolate Genome Sequence Database (BIGSDB), the prevalence and diversity of HpuAB among Neisseria were investigated. HpuAB was widely present in a range of Neisseria species whereas HmbR was mainly limited to the pathogenic species Neisseria meningitidis and Neisseria gonorrhoeae. Patterns of sequence variation in sequences from HpuAB proteins were suggestive of recombination and diversifying selection consistent with strong immune selection. HpuAB was subject to repeat-mediated phase variation in pathogenic Neisseria and the closely related non-pathogenic Neisseria species Neisseria lactamica and Neisseria polysaccharea but not in the majority of other commensal Neisseria species. These findings are consistent with HpuAB being subject to frequent genetic transfer potentially limiting the efficacy of this receptor as a vaccine candidate. PMID:23813677

  8. Quantitative determination of β-hydroxymethylbutyrate and leucine in culture media and microdialysates from rat brain by UHPLC-tandem mass spectrometry.

    PubMed

    Santos-Fandila, A; Zafra-Gómez, A; Barranco, A; Navalón, A; Rueda, R; Ramírez, M

    2014-05-01

    The main objective of the present work was to develop a method to determine β-hydroxymethylbutyrate (HMB) and leucine (Leu) in culture media and brain microdialysates. An accurate, selective, and cost-effective method, based on the use of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), was developed for the identification and quantification of both compounds. The method consisted of sample dilution, direct injection onto the chromatographic equipment, and quantification with a triple quadrupole mass spectrometer using an electrospray ionization interface in positive mode. The procedure and the UHPLC-MS/MS parameters were accurately optimized to achieve the highest recoveries and to enhance the analytical characteristics of the method. For chromatographic separation, an Acquity UPLC BEH Hilic column using acetonitrile-water gradient with formic acid as additive was employed. The total run time was 4 min. The limits of detection (LODs) obtained ranged from 0.01 to 0.04 μg mL(-1), and the limits of quantification (LOQs) ranged from 0.04 to 0.12 μg mL(-1). Precision (expressed as relative standard deviation) was lower than 15 %, and the determination coefficient (R (2)) was higher than 99.0 % with a residual deviation for each calibration point lower than ±25 %. Mean recoveries were between 85 and 115 %. The method was successfully applied to the analysis of both compounds, HMB and Leu, in samples obtained from an experiment of blood-brain barrier (BBB) passage in vitro and to an experiment of brain microdialysis in rats in vivo after an oral challenge with HMB to detect its appearance in the brain.

  9. Characterization of the inositol 1,4,5-trisphosphate-induced calcium release from permeabilized endocrine cells and its inhibition by decavanadate and p-hydroxymercuribenzoate.

    PubMed Central

    Föhr, K J; Scott, J; Ahnert-Hilger, G; Gratzl, M

    1989-01-01

    The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ compartment of endocrine cells was studied with alpha-toxin- and digitonin-permeabilized rat insulinoma (RINA2) and rat pheochromocytoma (PC12) cells. The Ca2+ uptake was ATP-dependent, and submicromolar concentrations of IP3 specifically released the stored Ca2+. Half-maximal Ca2+ release was observed with 0.25-0.5 mumol of IP3/l, and the amount of Ca2+ released due to IP3 could be enhanced by additional loading of the Ca2+ compartment. Consecutive additions of the same concentration of IP3 for 1-2 h always released the same amount of Ca2+ without desensitization, providing an ideal basis to further characterize the IP3-induced Ca2+ release. Here we describe for the first time a reversible inhibitory effect of decavanadate on the IP3-induced Ca2+ release. Among the vanadium species tested (decavanadate, oligovanadate and monovanadate), only decavanadate was inhibitory, with a half-maximal effect at 5 mumol/l in both cell types. The effect of decavanadate could be overcome by increasing the amount of sequestered Ca2+ or added IP3. Decavanadate did not affect the ATP-driven Ca2+ uptake but oligovanadate was inhibitory on Ca2+ uptake. p-Hydroxymercuribenzoate (pHMB) at concentrations between 10 and 30 mumol/l also inhibited the Ca2+ release due to IP3. Thiol compounds such as dithiothreitol (DTT; 1 mmol/l) added before pHMB removed all its inhibitory effect on the IP3-induced Ca2+ release, whereas the inhibition caused by decavanadate was unaffected by DTT. Thus, the decavanadate-dependent inhibition functions by a distinctly different mechanism than pHMB and could serve as a specific tool to analyse various aspects of the IP3-induced Ca2+ release within endocrine cells. PMID:2818578

  10. Human uroporphyrinogen III synthase: NMR-based mapping of the active site.

    PubMed

    Cunha, Luis; Kuti, Miklos; Bishop, David F; Mezei, Mihaly; Zeng, Lei; Zhou, Ming-Ming; Desnick, Robert J

    2008-05-01

    Uroporphyrinogen III synthase (URO-synthase) catalyzes the cyclization and D-ring isomerization of hydroxymethylbilane (HMB) to uroporphyrinogen (URO'gen) III, the cyclic tetrapyrrole and physiologic precursor of heme, chlorophyl, and corrin. The deficient activity of human URO-synthase results in the autosomal recessive cutaneous disorder, congenital erythropoietic porphyria. Mapping of the structural determinants that specify catalysis and, potentially, protein-protein interactions is lacking. To map the active site and assess the enzyme's possible interaction in a complex with hydroxymethylbilane-synthase (HMB-synthase) and/or uroporphyrinogen-decarboxylase (URO-decarboxylase) by NMR, an efficient expression and purification procedure was developed for these cytosolic enzymes of heme biosynthesis that enabled preparation of special isotopically-labeled protein samples for NMR characterization. Using an 800 MHz instrument, assignment of the URO-synthase backbone (13)C(alpha) (100%), (1)H(alpha) (99.6%), and nonproline (1)H(N) and (15)N resonances (94%) was achieved as well as 85% of the side-chain (13)C and (1)H resonances. NMR analyses of URO-synthase titrated with competitive inhibitors N(D)-methyl-1-formylbilane (NMF-bilane) or URO'gen III, revealed resonance perturbations of specific residues lining the cleft between the two major domains of URO synthase that mapped the enzyme's active site. In silico docking of the URO-synthase crystal structure with NMF-bilane and URO'gen III was consistent with the perturbation results and provided a 3D model of the enzyme-inhibitor complex. The absence of chemical shift changes in the (15)N spectrum of URO-synthase mixed with the homogeneous HMB-synthase holoenzyme or URO-decarboxylase precluded occurrence of a stable cytosolic enzyme complex.

  11. Combined Endometrial Ablation and Levonorgestrel Intrauterine System Use in Women With Dysmenorrhea and Heavy Menstrual Bleeding: Novel Approach for Challenging Cases.

    PubMed

    Papadakis, Efstathios P; El-Nashar, Sherif A; Laughlin-Tommaso, Shannon K; Shazly, Sherif A M; Hopkins, Matthew R; Breitkopf, Daniel M; Famuyide, Abimbola O

    2015-01-01

    To evaluate the feasibility and impact of levonorgestrel intrauterine system (LNG-IUS) on treatment failure after endometrial ablation (EA) in women with heavy menstrual bleeding (HMB) and dysmenorrhea at 4 years. Cohort study (Canadian Task Force II-2). An academic institution in the upper Midwest. All women with HMB and dysmenorrhea who underwent EA with combined placement of LNG-IUS (EA/LNG-IUS cohort, 23 women) after 2005 and an historic reference group from women who had EA alone (EA cohort, 65 women) from 1998 through the end of 2005. Radiofrequency EA, thermal balloon ablation, and LNG-IUS. The primary outcome was treatment failure defined as persistent pain, bleeding, and hysterectomy after EA at 4 years. The combined treatment failure outcome was documented in 2 patients (8.7%) in the EA/LNG-IUS group and 19 patients (29.2%) in the EA group with an unadjusted OR of .23 (95% CI, .05-1.08). After adjusting for known risk factors of failure, the adjusted OR was .19 (95% CI, .26-.88). None of the women who underwent EA/LNG-IUS had hysterectomy for treatment failure compared with 16 (24%) in the EA group (p = .009); postablation pelvic pain was documented in 1 woman (4.3%) in the EA/LNG-IUS group compared with 8 women (12.3%) in the EA group (p = .24). One woman in the EA/LNG-IUS group (4.3%) presented with persistent bleeding compared with 15 (23.1%) in the EA group (p = .059). Office removal of the intrauterine device was performed in 4 women with no complications. LNG-IUS insertion at the time of EA is feasible and can provide added benefit after EA in women with dysmenorrhea and HMB. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

  12. Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations

    PubMed Central

    Clavero, Sonia; Bishop, David F.; Haskins, Mark E.; Giger, Urs; Kauppinen, Raili; Desnick, Robert J.

    2010-01-01

    Human acute intermittent porphyria (AIP), the most common acute hepatic porphyria, is an autosomal dominant inborn error of heme biosynthesis due to the half-normal activity of hydroxymethylbilane synthase (HMB-synthase). Here, we describe the first naturally occurring animal model of AIP in four unrelated cat lines who presented phenotypically as congenital erythropoietic porphyria (CEP). Affected cats had erythrodontia, brownish urine, fluorescent bones, and markedly elevated urinary uroporphyrin (URO) and coproporphyrin (COPRO) consistent with CEP. However, their uroporphyrinogen-III-synthase (URO-synthase) activities (deficient in CEP) were normal. Notably, affected cats had half-normal HMB-synthase activities and elevated urinary 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), the deficient enzyme and accumulated metabolites in human AIP. Sequencing the feline HMB-synthase gene revealed different mutations in each line: a duplication (c.189dupT), an in-frame 3 bp deletion (c.842_844delGAG) identical to that causing human AIP and two missense mutations, c.250G>A (p.A84T) and c.445C>T (p.R149W). Prokaryotic expression of mutations c.842_844delGAG and c.445C>T resulted in mutant enzymes with <1% wild-type activity, whereas c.250G>A expressed a stable enzyme with ∼35% of wild-type activity. The discolored teeth from the affected cats contained markedly elevated URO I and III, accounting for the CEP-like phenocopy. In three lines, the phenotype was an autosomal dominant trait, while affected cats with the c.250G>A (p.A84T) mutation were homozygous, a unique recessive form of AIP. These animal models may permit further investigation of the pathogenesis of the acute, life-threatening neurological attacks in human AIP and the evaluation of therapeutic strategies. GenBank Accession Numbers: GQ850461–GQ850464. PMID:19934113

  13. Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations.

    PubMed

    Clavero, Sonia; Bishop, David F; Haskins, Mark E; Giger, Urs; Kauppinen, Raili; Desnick, Robert J

    2010-02-15

    Human acute intermittent porphyria (AIP), the most common acute hepatic porphyria, is an autosomal dominant inborn error of heme biosynthesis due to the half-normal activity of hydroxymethylbilane synthase (HMB-synthase). Here, we describe the first naturally occurring animal model of AIP in four unrelated cat lines who presented phenotypically as congenital erythropoietic porphyria (CEP). Affected cats had erythrodontia, brownish urine, fluorescent bones, and markedly elevated urinary uroporphyrin (URO) and coproporphyrin (COPRO) consistent with CEP. However, their uroporphyrinogen-III-synthase (URO-synthase) activities (deficient in CEP) were normal. Notably, affected cats had half-normal HMB-synthase activities and elevated urinary 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), the deficient enzyme and accumulated metabolites in human AIP. Sequencing the feline HMB-synthase gene revealed different mutations in each line: a duplication (c.189dupT), an in-frame 3 bp deletion (c.842_844delGAG) identical to that causing human AIP and two missense mutations, c.250G>A (p.A84T) and c.445C>T (p.R149W). Prokaryotic expression of mutations c.842_844delGAG and c.445C>T resulted in mutant enzymes with <1% wild-type activity, whereas c.250G>A expressed a stable enzyme with approximately 35% of wild-type activity. The discolored teeth from the affected cats contained markedly elevated URO I and III, accounting for the CEP-like phenocopy. In three lines, the phenotype was an autosomal dominant trait, while affected cats with the c.250G>A (p.A84T) mutation were homozygous, a unique recessive form of AIP. These animal models may permit further investigation of the pathogenesis of the acute, life-threatening neurological attacks in human AIP and the evaluation of therapeutic strategies. GenBank Accession Numbers: GQ850461-GQ850464.

  14. Synergistic Effects of Polyphenols and Methylxanthines with Leucine on AMPK/Sirtuin-Mediated Metabolism in Muscle Cells and Adipocytes

    PubMed Central

    Bruckbauer, Antje; Zemel, Michael B.

    2014-01-01

    The AMPK-Sirt1 pathway is an important regulator of energy metabolism and therefore a potential target for prevention and therapy of metabolic diseases. We recently demonstrated leucine and its metabolite β-hydroxy-β-methylbutyrate (HMB) to synergize with low-dose resveratrol (200 nM) to activate sirtuin signaling and stimulate energy metabolism. Here we show that leucine exerts a direct effect on Sirt1 kinetics, reducing its Km for NAD+ by >50% and enabling low doses of resveratrol to further activate the enzyme (p = 0.012). To test which structure elements of resveratrol are necessary for synergy, we assessed potential synergy of structurally similar and dissimilar polyphenols as well as other compounds converging on the same pathways with leucine using fatty acid oxidation (FAO) as screening tool. Dose-response curves for FAO were constructed and the highest non-effective dose (typically 1–10 nM) was used with either leucine (0.5 mM) or HMB (5 µM) to treat adipocytes and myotubes for 24 h. Significant synergy was detected for stilbenes with FAO increase in adipocytes by 60–70% (p<0.05) and in myotubes >2000% (p<0.01). Sirt1 and AMPK activities were stimulated by ∼65% (p<0.001) and ∼50% (p<0.03), respectively. Similarly, hydroxycinnamic acids and derivatives (chlorogenic, cinnamic, and ferulic acids) combined with leucine/HMB increased FAO (300–1300%, p<0.01), AMPK activity (50–150%, p<0.01), and Sirt1 activity (∼70%, p<0.001). In contrast, more complex polyphenol structures, such as ellagic acid and epigallocatechin gallate required higher concentrations (>1 µM) and exhibited little or no synergy. Thus, the six-carbon ring structure bound to a carboxylic group seems to be a necessary element for leucine/HMB synergy with other stilbenes and hydroxycinnamic acids to stimulate AMPK/Sirt1 dependent FAO; these effects occur at concentrations that produce no independent effects and are readily achievable via oral administration. PMID:24551237

  15. Use of mixed-treatment-comparison methods in estimating efficacy of treatments for heavy menstrual bleeding

    PubMed Central

    2013-01-01

    Background A variety of pharmacological and surgical treatments have been developed for heavy menstrual bleeding (HMB), which can have negative physical, social, psychological, and economic consequences. We conducted a systematic literature review and mixed-treatment-comparison (MTC) meta-analysis of available data from randomized controlled trials (RCTs) to derive estimates of efficacy for 8 classes of treatments for HMB, to inform health-economic analysis and future studies. Methods A systematic review identified RCTs that reported data on menstrual blood loss (MBL) at baseline and one or more follow-up times. Eight treatment classes were considered: COCs, danazol, endometrial ablation, LNG-IUS, placebo, progestogens given for less than 2 weeks out of 4 during the menstrual cycle, progestogens given for close to 3 weeks out of 4, and TXA. The primary measure of efficacy was the proportion of women who achieved MBL < 80 mL per cycle (month), as measured by the alkaline hematin method. A score less than 100 on an established pictorial blood-loss assessment chart (PBAC) was considered an acceptable substitute for MBL < 80 mL. Estimates of efficacy by treatment class and time were obtained from a Bayesian MTC model. The model also included effects for treatment class, study, and the combination of treatment class and study and an adjustment for baseline mean MBL. Several methodological challenges complicated the analysis. Some trials reported various summary statistics for MBL or PBAC, requiring estimation (with less precision) of % MBL < 80 mL or % PBAC < 100. Also, reported follow-up times varied substantially. Results The evidence network involved 34 RCTs, with follow-up times from 1 to 36 months. Efficacy at 3 months of follow-up (estimated as the posterior median) ranged from 87.5% for the levonorgestrel-releasing intrauterine system (LNG-IUS) to 14.2% for progestogens administered for less than 2 weeks out of 4 in the menstrual cycle. The 95% credible intervals

  16. Concentrations of putrescine, spermidine, and spermine in duodenum and pancreas as affected by the ratio of arginine to lysine and source of methionine in broilers under heat stress.

    PubMed

    Gonzalez-Esquerra, R; Leeson, S

    2006-08-01

    An experiment was designed to investigate the effect of Arg, Lys, Met, and environmental temperature on broiler performance and associated changes in duodenal and pancreatic polyamines. Two groups of 26-d-old Ross male broilers raised under thermoneutral (TN) conditions were reallocated to 4 rooms kept at heat stress (HS) or TN. Birds were fed equimolar amounts of 2-hydroxy-4-(methylthio) butanoic acid (HMB) or DL-Met (DLM) at requirement levels with Arg:Lys at 0.95 or 1.40. Twelve replicates of 4 birds were offered each diet ad libitum. Body weight gain, efficiency of dietary CP accretion (CPE), feed intake, and feed conversion ratio were ascertained from 26 to 33 d and from 34 to 47 d of age. One bird per cage was killed at 33 and 47 d, and samples of duodenum and pancreas were assayed for putrescine, spermidine, and spermine (Spm), together with estimates of duodenal villus height. From 26 to 33 d, birds fed HMB performed better than those fed DLM, but only at TN conditions. From 34 to 47 d, feeding HMB tended to optimize CPE when added to diets high in Arg. However, lower CPE was obtained when HMB was added to low-Arg diets, whereas birds fed DLM were unaffected by these treatments (P < 0.10). Methionine source, Arg:Lys, or both affected the concentrations of duodenal and pancreatic polyamines, with some changes correlating with performance variables during HS (P > 0.05). It was found that HS caused lower tissue spermidine (P < 0.001) and higher pancreatic Spm (P = 0.08) from 34 to 47 d. Putrescine concentrations were affected by diet and HS, depending on tissue and experimental period. Pancreatic Spm correlated negatively with changes in CPE influenced by Arg:Lys by Met source interaction in chronically heat-stressed birds. The possible association between polyamine metabolism and some of the effects of the Arg:Lys by Met source interaction observed in chronically stressed birds deserves further investigation.

  17. Fatty Acid Synthase and Acetyl-CoA Carboxylase Are Expressed in Nodal Metastatic Melanoma But Not in Benign Intracapsular Nodal Nevi.

    PubMed

    Saab, Jad; Santos-Zabala, Maria Laureana; Loda, Massimo; Stack, Edward C; Hollmann, Travis J

    2017-06-13

    Melanoma is a potentially lethal form of skin cancer for which the current standard therapy is complete surgical removal of the primary tumor followed by sentinel lymph node biopsy when indicated. Histologic identification of metastatic melanoma in a sentinel node has significant prognostic and therapeutic implications, routinely guiding further surgical management with regional lymphadenectomy. While melanocytes in a lymph node can be identified by routine histopathologic and immunohistochemical examination, the distinction between nodal nevus cells and melanoma can be morphologically problematic. Previous studies have shown that malignant melanoma can over-express metabolic genes such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). This immunohistochemical study aims to compare the utility of FASN and ACC in differentiating sentinel lymph nodes with metastatic melanomas from those with benign nodal nevi in patients with cutaneous melanoma. Using antibodies against FASN and ACC, 13 sentinel lymph nodes from 13 patients with metastatic melanoma and 14 lymph nodes harboring benign intracapsular nevi from 14 patients with cutaneous malignant melanoma were examined. A diagnosis of nodal melanoma was based on cytologic atypia and histologic comparison with the primary melanoma. All nodal nevi were intracapsular and not trabecular. Immunohistochemistry for Melan-A, S100, human melanoma black 45 (HMB45), FASN, and ACC were performed. The percentage of melanocytes staining with HMB45, FASN, and ACC was determined and graded in 25% increments; staining intensity was graded as weak, moderate, or strong. All metastatic melanomas tested had at least 25% tumor cell staining for both FASN and ACC. Greater than 75% of the tumor cells stained with FAS in 7/13 cases and for ACC in 5/12 cases. Intensity of staining was variable; strong staining for FASN and ACC was observed in 69% and 50% of metastatic melanoma, respectively. HMB45 was negative in 40% of nodal

  18. Dietary supplements selected by young people exercising in fitness rooms in Kraków and environs.

    PubMed

    Chłopicka, Joanna; Wandas, Piotr; Zachwieja, Zofia

    2007-01-01

    The purpose of this study was to determine the prevalence of the use of dietary supplements among the young people exercising in fitness rooms in Krak6w and environs. In this study, 81% of the population used some form of dietary supplement; nutritional supplements were used by 21% of women and 60% of men, and were used most frequently by young people 21-25 years of age. The most popular supplement s were creatine, (20%) and HMB-beta-hydroxy-betamethylbutyrate (19%). Only 14% of the respondents asked for the opinion of qualified personnel, such as doctors, pharmacists or dieticians.

  19. Antibacterial activities of the methanol extracts, fractions and compounds from Harungana madagascariensis Lam. ex Poir. (Hypericaceae).

    PubMed

    Tankeo, Simplice B; Damen, Francois; Sandjo, Louis P; Celik, Ilhami; Tane, Pierre; Kuete, Victor

    2016-08-22

    Harungana madagascariensis Lam. ex Poir. (Hypericaceae) is used in folk medicine to treat a variety of human ailments, mainly antibacterial, antifungal, antiviral and viral infections. In the present study, the methanol extract from the leaves (HML) and bark (HMB) of this plant as well as fractions (HMBa-c), sub-fractions (HMBa1-5) and compounds isolated from HMBa and HMBb namely betulinic acid (1), madagascin (2), ferruginin A (3) and Kaempferol-3-O-β-d-glucopyranoside (4) were tested for their antimicrobial activities against a panel of 28 g-negative bacteria including multidrug resistant (MDR) phenotypes. The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; column chromatography was used for the fractionation and purification of the bark extract whilst the chemical structures of compounds were determined using spectroscopic techniques. Crude extract HMB together with fraction HMBa and sub-fraction HMBa3 were active on the 28 tested bacterial strains. HML as well as fractions HMBb, HMBc and sub-fractions HMBa1, HMBa2, HMBa4 and HMBa5 were selectively active. MIC values below or equal to 1024µg/mL were recorded with these samples on 92.9% (for HML and HMBa 4), 82.1% (for HMBb), 78.6% (for HMBa2), 50.0% (for HMBa5) and 42.9% (for HMBc) tested bacteria. For crude material, the lowest MIC value below 8µg/mL was obtained with HMB against Escherichia coli ATCC10536 and W3110 strains, and with sub-fraction HMBa3 against Klebsiella pneumoniae K2 strains. MIC values below 10µg/mL were recorded with compound 3 against E. coli ATCC10536, Enterobacter aerogenes ATCC13048 and EA294, Pseudomonas aeruginosa PA01, K. pneumoniae K2 and Kp55 and Enterobacter cloacae BM67. Harungana madagascariensis is a potential source of antimicrobial drugs to fight against MDR bacteria. The anthranol 3 is the main antibacterial constituents of the bark of the plant. HMB and compound

  20. Primary angiomatoid melanoma as an exceptional morphologic pattern in cutaneous melanoma. A case report and review of the literature.

    PubMed

    Ramos-Rodríguez, G; Ortiz-Hidalgo, C

    2015-04-01

    We report a case of angiomatoid melanoma on the right thigh of a 59-year-old man. The histologic growth pattern of the tumor mimicked vascular proliferation, and the cells lining the pseudovascular spaces were positive for protein S-100, HMB-45, and MITF-1. The differential diagnosis is with angiosarcoma and pseudovascular adenoid squamous cell carcinoma. The case we present is the fifth reported to date. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

  1. Renal Pelvis Leiomyoma- An Infrequent Clinical Case.

    PubMed

    Romano, Fernando Ugarte-Y; González-Serrano, Adolfo; Moreno-Aranda, Jorge

    2017-05-01

    Renal pelvis leiomyomas are infrequent benign tumours. These tumours are more frequent in women, usually asymptomatic and difficult to distinguish from malign kidney masses. A 27-year-old female presented with an asymptomatic renal mass discovered after abdominal ultrasound during routine check-up. Percutaneous renal biopsy was performed and reported urothelial carcinoma. After open nephroureterectomy, histopathological evaluation and immunohistochemistry were positive for Smooth Muscle Actin (SMA), Ki67 <5%, and negative for cytokeratin and HMB-45. Thus, confirming the diagnosis of renal leiomyoma. The diagnosis of these infrequent tumours is often difficult and it is usually made by immunohistochemistry after surgical treatment.

  2. Entamoeba histolytica: increase of enterotoxicity and of 53- and 75-kDa cysteine proteinases in a clone of higher virulence.

    PubMed

    Navarro-García, F; Chávez-Dueñas, L; Tsutsumi, V; Posadas del Río, F; López-Revilla, R

    1995-05-01

    We compared the enterotoxicity and cysteine proteinases (CP) of the low-virulence Entamoeba histolytica HM1 strain with the highly virulent 1659 clone, derived from HM1 by hamster liver passages. Enterotoxicity of 50,000 freeze-thawed trophozoites was determined on 0.28-cm2 intestinal segments mounted in Ussing chambers; CP activity of Nonidet-P40 amebal lysates was assayed by gelatin-sodium dodecyl sulfate-polyacrylamide gel electrophoresis and carbobenzoxy-L-arginine-L-arginyl-p-nitroaniline, a CP-specific substrate. Treatment of gerbil cecum segments with amebal lysates caused an immediate fall of their electrophysiologic properties (potential difference, short-circuit current, and transmural resistance) whose decay rates were clearly faster with 1659 than with HM1 lysates. Nonimmune and immune antiamebic human sera and the CP-specific inhibitor E-64 (trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane) prevented the fall of the electrophysiologic properties. Gelatinases, less active in HM1 than in 1659 trophozoites, were better preserved in lysates containing 10 mM p-hydroxymercuribenzoate (pHMB) to prevent autoproteolysis: in lysates without pHMB nearly no gelatinase bands were observed in HM1 samples, whereas intense 30K, 35K, 44K, and 75K bands were seen in 1659 samples; in lysates with pHMB only 53K and 75K bands were found that were much more intense in 1659 samples, 75K being barely visible in HM1 samples. The overall CP activity was 17 times higher in 1659 than in HM1 lysates, was inhibited by E-64 (mean inhibitory dose, 20 microM), was stimulated by 2-mercaptoethanol (ME) 3.7 times in HM1 and 2.4 times in 1659 lysates, and was reactivated by ME in lysates containing pHMB. Most of the CP activity in HM1 lysates sedimented at 15,600g but predominated in 1659 supernatants. The increase of E. histolytica virulence thus correlates with a remarkable increase both of in vitro enterotoxicity and of two CPs (53K and 75K), suggesting that these proteinases are

  3. Immunohistochemical features of multifocal melanoacanthoma in the hard palate: a case report

    PubMed Central

    2013-01-01

    Background Melanoacanthoma (MA) has been described in the oral mucosa as a solitary lesion or, occasionally, as multiple lesions. MA mainly affects dark skinned patients and grows rapidly, showing a plane or slightly raised appearance and a brown to black color. The differential diagnosis includes oral nevi, amalgam tattoos, and melanomas. We report here the case of a 58-year-old black woman who presented multiple pigmented lesions on the hard palate. Case presentation Based on the differential diagnosis of melanoma, a punch biopsy (4 mm in diameter) was performed. The material was fixed in 10% formalin, embedded in paraffin, and stained with hematoxylin-eosin or submitted to immunohistochemical analysis. Immunohistochemistry using antibodies against protein S-100, melan-A, HMB-45, MCM-2, MCM-5, Ki-67 and geminin was performed. Immunohistochemical analysis revealed strong cytoplasmic immunoreactivity of dendritic melanocytes for proteinS-100, HMB-45 and melan-A.Positive staining for proliferative markers (MCM-2, MCM-5, Ki-67) was only observed in basal and suprabasal epithelial cells, confirming the reactive etiology of the lesion. The diagnosis was oral Melanoacanthoma (MA). Conclusion The patient has been followed up for 30 months and shows no clinical alterations. MA should be included in the differential diagnosis of pigmented lesions of the oral cavity. PMID:23356913

  4. Immunohistochemical and molecular pathology of ocular uveal melanocytoma: evidence for somatic GNAQ mutations.

    PubMed

    Mudhar, Hardeep Singh; Doherty, Rachel; Salawu, Abdulazeez; Sisley, Karen; Rennie, Ian G

    2013-07-01

    Intraocular melanocytoma is a rare naevus variant that can be located at the optic disc or within the uvea, and belongs to the group of non-epithelial-associated melanocytic lesions. We wanted to gain an understanding of the role of GNAQ, GNA11 and BRAF V600E in the pathogenesis of uveal melanocytoma and in cases of transformation to uveal melanoma and also to perform a differential immunohistochemical study comparing melanocytoma with uveal melanoma. Two patients were identified with melanocytoma, one of which had transformed to melanoma. In the latter case, the melanocytoma exhibited an immunophenotype that featured nuclear p27 and no HMB45 staining, with very low Cyclin D1 expression compared with the melanoma that featured little nuclear but more cytoplasmic p27 positivity, much higher Cyclin D1 expression and HMB45 positivity. The melanocytomas were negative for CD68 allowing distinction from melanophages. Both melanocytomas and the melanoma harboured mutations in GNAQ, with no mutations of GNA11 or BRAF V600E. GNAQ mutations are present in uveal melanocytomas and in a case of transformation to melanoma, implicating GNAQ-dependent mitogen activation signals, in the pathogenesis of uveal melanocytoma. This assists in explaining why a proportion of uveal melanocytoma can transform to uveal melanoma, known to harbour high-frequency GNAQ mutations at exon 5, codon 209.

  5. Methionine salvage pathway in relation to ethylene biosynthesis

    SciTech Connect

    Miyazaki, J.H.

    1987-01-01

    The recycling of methionine during ethylene biosynthesis (the methionine cycle) was studied. During ethylene biosynthesis, the H/sub 3/CS-group of S-adenosylmethionine (SAM) is released at 5'-methylthioadenosine (MTA), which is recycled to methionine via 5'-methylthioribose (MTS). In mungbean hypocotyls and cell-free extracts of avocado fruit, (/sup 14/C)MTR was converted to labeled methionine via 2-keto-4-methylthiobutyric acid (KMB) and 2-hydroxy-4-methylthiobutyric acid (HMB) as intermediates. Radioactive tracer studies showed that KMB was converted readily in vivo and in vitro to methionine, while HMB was converted much more slowly. The conversion of KMB to methionine by dialyzed avocado extract required an amino group donor. Among several potential donors tested, L-glutamine was the most efficient. Incubation of (ribose-U-/sup 14/C)MTR with avocado extract resulted in the production of (/sup 14/C)formate, with little evolution of other /sup 14/C-labeled one-carbon compounds, indicating that the conversion of MTR to KMB involves a loss of formate, presumably from C-1 of MTR.

  6. Acute intermittent porphyria: A single-base deletion and a nonsense mutation in the human hydroxymethylbilane synthase gene, predicting truncations of the enzyme polypeptide

    SciTech Connect

    Lee, G.L.; Astrin, K.H.; Desnick, R.J.

    1995-08-28

    Acute intermittent porphyria (AIP) is an autosomal-dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase (HMB-synthase). AIP is an ecogenetic condition, since the life-threatening acute attacks are precipitated by various factors, including drugs, alcohol, fasting, and certain hormones. Biochemical diagnosis is problematic, and the identification of mutations in the HMB-synthase gene provides accurate detection of presymptomatic heterozygotes, permitting avoidance of the acute precipitating factors. By direct solid-phase sequencing, two mutations causing AIP were identified, an adenine deletion at position 629 in exon 11(629delA), which alters the reading frame and predicts premature truncation of the enzyme protein after amino acid 255, and a nonsense mutation in exon 12 (R225X). These mutations were confirmed by either restriction enzyme analysis or family studies of symptomatic patients, permitting accurate presymptomatic diagnosis of affected relatives. 29 refs., 2 figs.

  7. Iron deficiency and iron deficiency anaemia in women.

    PubMed

    Percy, Laura; Mansour, Diana; Fraser, Ian

    2017-04-01

    Iron deficiency (ID) is the most common micronutrient deficiency worldwide with >20% of women experiencing it during their reproductive lives. Hepcidin, a peptide hormone mostly produced by the liver, controls the absorption and regulation of iron. Understanding iron metabolism is pivotal in the successful management of ID and iron deficiency anaemia (IDA) using oral preparations, parenteral iron or blood transfusion. Oral preparations vary in their iron content and can result in gastrointestinal side effects. Parenteral iron is indicated when there are compliance/tolerance issues with oral iron, comorbidities which may affect absorption or ongoing iron losses that exceed absorptive capacity. It may also be the preferred option when rapid iron repletion is required to prevent physiological decompensation or given preoperatively for non-deferrable surgery. As gynaecologists, we focus on managing women's heavy menstrual bleeding (HMB) and assume that primary care clinicians are treating the associated ID/IDA. We now need to take the lead in diagnosing, managing and initiating treatment for ID/IDA and treating HMB simultaneously. This dual management will significantly improve their quality of life. In this chapter we will summarise the importance of iron in cellular functioning, describe how to diagnose ID/IDA and help clinicians choose between the available treatment options. Copyright © 2016. Published by Elsevier Ltd.

  8. Human Milk Composition and Preservation: Evaluation of High-pressure Processing as a Nonthermal Pasteurization Technology.

    PubMed

    Sousa, Sílvia G; Delgadillo, Ivonne; Saraiva, Jorge A

    2016-01-01

    Human milk is seen not only as a food, but as a functional and dynamic biologic system. It provides nutrients, bioactive components, and immune factors, promoting adequate and healthy growth of newborn infants. When mothers cannot supply their children, donated breast milk is the nutrition recommended by the World Health Organization, as it is a better alternative than infant formula. However, because of the manner in which donor milk is handled in human milk banks (HMB) many of the properties ascribed to mother's own milk are diminished or destroyed. The major process responsible for these losses is Holder pasteurization. High-pressure processing (HPP) is a novel nonthermal pasteurization technology that is being increasingly applied in food industries worldwide, primarily as an alternative to thermal treatment. This is due to its capacity to inactivate microorganisms while preserving both nutritional and bioactive components of foods. This review describes human milk composition and preservation, and critically discusses HMB importance and practices, highlighting HPP as a potential nonthermal pasteurization technology for human milk preservation. HPP technology is described and the few currently existing studies of its effects in human milk are presented.

  9. "Malignant" uterine perivascular epithelioid cell tumor, pelvic lymph node lymphangioleiomyomatosis, and gynecological pecomatosis in a patient with tuberous sclerosis: a case report and review of the literature.

    PubMed

    Liang, Sharon X; Pearl, Michael; Liu, Jingxuan; Hwang, Sonia; Tornos, Carmen

    2008-01-01

    We report a case of uterine perivascular epithelioid cell tumor (PEComa) with malignant histological features in a 59-year-old woman with tuberous sclerosis (TBS). The patient also had extrapulmonary lymphangioleiomyomatosis involving pelvic lymph nodes, myometrium, cervix, and ovary ("pecomatosis"). The uterine tumor measured 2.6 cm and had marked nuclear pleomorphism, necrosis, and 2 mitoses per 50 high-powered field, with an occasional atypical mitosis and infiltrative borders. The nonneoplastic myometrium, the cervical wall, and the hilum of the ovary had multiple clusters of bland-looking epithelioid clear cells that ranged from 1 to 5 mm (pecomatosis). The uterine tumor cells were positive for HMB-45 (90%), Melan-A (70%), smooth muscle actin (50%), and estrogen receptor (30%). Of the 16 pelvic lymph nodes excised, 3 were involved with lymphangioleiomyomatosis that was positive for HMB-45 and estrogen receptor. This is only the second reported PEComa associated with pecomatosis and the fourth PEComa described in a patient with TBS. The clinical significance of pecomatosis is still uncertain but seems to be seen only in patients with TBS.

  10. Improving care and treatment options for women and girls with bleeding disorders.

    PubMed

    Kulkarni, Roshni

    2015-12-01

    Women and girls may experience increased bleeding symptoms as carriers of haemophilia. They can also be affected by other hereditary bleeding diatheses such as von Willebrand disease, platelet dysfunction defects or deficiencies of coagulation factors (F) such as FI, FII, FV, FVII, FX, FXI and FXIII. In addition to general bleeding symptoms, such disorders pose unique problems for women due to their impact on reproductive health. Women and adolescent girls with undiagnosed bleeding disorders frequently experience heavy menstrual bleeding (HMB; menorrhagia), leading to impairment of daily activities. Other gynaecological and obstetric manifestations, for example miscarriage, bleeding during pregnancy and postpartum haemorrhage (PPH), can occur. Treatment for HMB should consider patient wishes relating to preservation of fertility, and management options include hormonal measures, desmopressin, antifibrinolytics, platelet concentrate transfusions and clotting factor therapy. During pregnancy, monitoring clotting factor levels informs the need for prophylactic therapy; subsequent haemostatic cover can minimise PPH. Under-recognition of bleeding disorders in females may lead to inappropriate, or lack of, treatment. This may be avoided by increased disease awareness, prompt and accurate diagnosis, and a multidisciplinary approach to patient care. This review considers the range of hereditary bleeding disorders that may affect women and adolescent girls, and their evaluation and management. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Fine needle aspiration biopsy to reestablish cell culture in an animal model of uveal melanoma.

    PubMed

    Correa, Zelia Maria da Silva; Marshall, Jean-Claude; Souza Filho, João Pessoa; Odashiro, Alexandre Nakao; Burnier Jr, Miguel Noel

    2009-01-01

    To access the reliability of fine-needle aspiration biopsy in harvesting a sufficient amount of viable melanoma cells to establish a cell culture and maintain a melanoma cell line from an animal model of uveal melanoma. For this study, fifteen male New Zealand albino rabbits had their right eye surgically inoculated with uveal melanoma cell line 92.1. The animals were immunosupressed with cyclosporine A using a dose schedule previously published. The animals were followed for 12 weeks. Intraocular tumor growth was monitored weekly by indirect ophthalmoscopy. After the fourth week, one animal was sacrificed per week preceded by fine-needle aspiration biopsy using a sharp 25-gauge, 1-inch long needle. Two separate aspirates were made from different areas of the tumor. Each aspirate was flushed to a separate cell culture media and sent for cell culture. The cells were frozen after two weeks when there were at least 1 million cells, which is enough to maintain a cell line. Cells were defrosted for HMB-45 immuno-stains to confirm the melanoma origin. Cell growth was observed from the samples harvested from 11 out of the 15 animals inoculated with uveal melanoma. All cell cultures, after defrost, immunoassayed positive for HMB-45. Fine needle aspiration biopsy seems to be a reliable method to harvest cells from solid intraocular melanomas in an animal model, to establish cell culture and to maintain a melanoma cell line.

  12. Perivascular Epithelioid Cell Tumor of the Ileum Presenting as Diverticulitis

    PubMed Central

    Unluoglu, Saime; Bayol, Umit; Korkmaz, Nilay; Ozenen, Bekir; Ipekci, Fuat; Pala, Emel Ebru

    2012-01-01

    Perivascular epithelioid cell tumors (PEComas) are a group of rare mesenchymal neoplasms. Gastrointestinal PEComas are exceptionally rare, there being only a few case reports in the literature involving the colon and small intestine. Nearly all PEComas show immunoreactivity for both melanocytic (HMB45 and/or Melan-A) and smooth muscle (actin and/or desmin) markers. A 36-year-old male was admitted to the hospital with acut- abdomen. At laparatomy, a nodular mass protruding from the ileum which clinically simulated a diverticulitis was noticed. Gross examination of the specimen revealed a 2 × 1,5 × 1 cm secondarily ulcerated, solid, nodular, gray white tumor mass in the ileal wall. Histologically, tumor cells were composed of nests of round-polygonal epithelioid cells with abundant clear to slightly eosinophilic granular cytoplasm and round vesicular nuclei. The nests were separated by thin fibrovascular septa. Minimal necrosis and low mitotic activity were noticed in the tumor. Immunohistochemically, tumor cells were positive for SMA, HMB45, and Melan-A and negative for CD10, RCC, CD45, CD117, CD34, EMA, and Desmin. Diagnosis was PEComa of the ileum. We report the case of ileal PEComa to remind the unusual presentation (diverticulitis) of these tumors, besides rarity and diagnostic difficulties. PMID:22953133

  13. Nutritional supplements to increase muscle mass.

    PubMed

    Clarkson, P M; Rawson, E S

    1999-07-01

    Although nutritional supplements purported to increase muscle mass are widely available at health food stores, gyms, by mail order, and over the Internet, many of these supplements have little or no data to support their claims. This article reviews the theory and research behind popular nutritional supplements commonly marketed as muscle mass builders. Included are the minerals chromium, vanadyl sulfate, and boron, the steroid hormone dehydroepiandrosterone (DHEA), beta-methyl-hydroxy-beta-methylbutyrate (HMB), creatine, protein supplements, and amino acids. Research has shown that chromium vanadyl sulfate, and boron do not appear to be effective in increasing lean body mass. The few studies examining DHEA have not supported the claim of increased muscle gain. Preliminary work on HMB supports an anticatabolic effect, but only one human study is currently available. Many studies reported increased body mass and several have reported increased lean body mass following creatine ingestion. This weight gain is most likely water retention in muscle but could also be due to some new muscle protein. Although athletes have a greater protein requirement than sedentary individuals, this is easily obtained through the diet, negating the use of protein supplements. Studies on amino acids have not supported their claim to increase growth hormone or insulin secretion. Nutritional supplements can be marketed without FDA approval of safety or effectiveness. Athletes who choose to ingest these supplements should be concerned with unsubstantiated claims, questionable quality control, and safety of long-term use.

  14. Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis.

    PubMed

    Nissen, Steven L; Sharp, Rick L

    2003-02-01

    The purpose of this study was to quantify which dietary supplements augment lean mass and strength gains during resistance training. Peer-reviewed studies between the years 1967 and 2001 were included in the analysis if they met a predetermined set of experimental criteria, among which were at least 3-wk duration and resistance-training 2 or more times a week. Lean mass and strength were normalized for meta-analysis by conversion to percent change per week and by calculating the effect size for each variable. Of the 250 supplements examined, only 6 had more than 2 studies that met the criteria for inclusion in the meta-analysis. Creatine and beta-hydroxy-beta-methylbutyrate (HMB) were found to significantly increase net lean mass gains of 0.36 and 0.28%/wk and strength gains of 1.09 and 1.40%/wk (P < 0.05), respectively. Chromium, dehydroepiandrosterone, androstenedione, and protein did not significantly affect lean gain or strength. In conclusion, two supplements, creatine and HMB, have data supporting their use to augment lean mass and strength gains with resistance training.

  15. Submicrodeterminations of thiols, disulphides and thiol esters in serum by using o-hydroxymercuribenzoic acid and dithiofluorescein

    PubMed Central

    Wroński, Mieczysław

    1967-01-01

    1. Methods are described for selective estimation of thiols, disulphides and thiol esters in standard solutions and in serum. The methods are based on the reaction with the excess of o-hydroxymercuribenzoic acid (HMB) in alkaline solution with subsequent addition of dithiofluorescein in excess and determination of the extinction at 588mμ. The sensitivity of the methods amounts to 1·5×10−9g.equiv. in 5ml. of final solution. Of results obtained on standard solutions 80% have the errors within the range ±4%. 2. It has been found that serum contains an unidentified substance (substance X) producing green complexes with dithiofluorescein which undergo decomposition on addition of formaldehyde. The correction for substance X must be estimated in a separate sample and taken into account. The concentration of substance X can be calculated from extinctions measured at 588mμ and 635mμ in the presence of dithiofluorescein in excess. 3. The selective determination of thiols and disulphides is based on different reaction rates with formaldehyde. The complexes between HMB and cysteine can be selectively decomposed by formaldehyde, and free glutathione can be selectively removed by formaldehyde in the presence of protein thiols. 4. Thiols are determined in the presence of triethylamine, thiols plus disulphides in the presence of triethylamine and sulphite, and thiols plus thiol esters in the presence of dimethylamine, with subsequent addition of ammonium sulphate. PMID:6049936

  16. Nutritional interventions in sarcopenia: a critical review.

    PubMed

    Hickson, Mary

    2015-11-01

    The aim of the present paper is to critically review the details of the published nutrition intervention trials, with and without exercise, targeting sarcopenia. Sarcopenia is the loss of muscle mass, strength and/or performance with age. Since amino acids and energy are required for muscle synthesis it is possible that nutritional intake influences sarcopenia. Nutritional studies are challenging to carry out because of the complexity of modulating dietary intake. It is very difficult to change one nutrient without influencing many others, which means that many of the published studies are problematic to interpret. The studies included evaluate whole protein, essential amino acids and β-hydroxyl β-methylbutyrate (HMB). Whole-protein supplementation failed to show a consistent effect on muscle mass, strength or function. This can be explained by the variations in study design, composition of the protein supplement and the failure to monitor voluntary food intake, adherence and baseline nutritional status. Essential amino-acid supplements showed an inconsistent effect but there are only two trials that have significant differences in methodology and the supplement used. The HMB studies are suggestive of a beneficial effect on older adults, but larger well-controlled studies are required that measure outcomes relevant to sarcopenia, ideally in sarcopenic populations. The issues of timing and distribution of protein intake, and increased splanchnic amino-acid sequestration are discussed, and recommendations for future trials are made.

  17. Assessment of an Electronic Intervention in Young Women with Heavy Menstrual Bleeding.

    PubMed

    Dietrich, Jennifer E; Yee, Donald L; Santos, Xiomara M; Bercaw-Pratt, Jennifer L; Kurkowski, Jennifer; Soni, Heather; Lee-Kim, Youngna J; Shah, Mona D; Mahoney, Donald; Srivaths, Lakshmi V

    2016-10-15

    STUDY OBJECTIVE, DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Bleeding disorders (BD) occur in up to 50% of adolescents with heavy menstrual bleeding (HMB). This presents unique challenges to health care providers because of the complexity of treating the condition and such complexity can result in difficulty with patients understanding basic information about their condition, limit communication with medical providers, and patient compliance. The aim of the study was to use an electronic approach to enhance patient compliance with medications used to treat their HMB, and to provide educational access to adolescents with BD. This was a prospective cohort study involving patients in a Young Women's Bleeding Disorder Clinic at a single children's hospital. Subjects were given an iPod Touch (Apple Inc, Cupertino, CA) device (ITD), preloaded with the iPeriod (Winkpass Creations) application. Participants recorded information about their BD that they learned about on BD Web sites, and menses, and medications. Electronic and charted data were collected to monitor compliance with prescribed treatment regimens. All ITD allowed Wi-Fi access to allow teens to explore BD Web sites and knowledge was assessed.

  18. The role of leucine and its metabolites in protein and energy metabolism.

    PubMed

    Duan, Yehui; Li, Fengna; Li, Yinghui; Tang, Yulong; Kong, Xiangfeng; Feng, Zemeng; Anthony, Tracy G; Watford, Malcolm; Hou, Yongqing; Wu, Guoyao; Yin, Yulong

    2016-01-01

    Leucine (Leu) is a nutritionally essential branched-chain amino acid (BCAA) in animal nutrition. It is usually one of the most abundant amino acids in high-quality protein foods. Leu increases protein synthesis through activation of the mammalian target of rapamycin (mTOR) signaling pathway in skeletal muscle, adipose tissue and placental cells. Leu promotes energy metabolism (glucose uptake, mitochondrial biogenesis, and fatty acid oxidation) to provide energy for protein synthesis, while inhibiting protein degradation. Approximately 80 % of Leu is normally used for protein synthesis, while the remainder is converted to α-ketoisocaproate (α-KIC) and β-hydroxy-β-methylbutyrate (HMB) in skeletal muscle. Therefore, it has been hypothesized that some of the functions of Leu are modulated by its metabolites. Both α-KIC and HMB have recently received considerable attention as nutritional supplements used to increase protein synthesis, inhibit protein degradation, and regulate energy homeostasis in a variety of in vitro and in vivo models. Leu and its metabolites hold great promise to enhance the growth and health of animals (including humans, birds and fish).

  19. Epithelioid angiomyolipoma of the kidney.

    PubMed

    Kato, Ikuma; Inayama, Yoshiaki; Yamanaka, Shoji; Ohshiro, Hisashi; Gomi, Kiyoshi; Shirai, Sumiko; Aoki, Ichiro; Uemura, Hiroji; Miyoshi, Yasuhide; Kubota, Yoshinobu; Yao, Masahiro; Nagashima, Yoji

    2009-01-01

    Epithelioid angiomyolipoma (eAMLoma) is an uncommon renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis (TSC). It is composed of polygonal large-sized tumor cells arranged in an epithelioid manner. Differential diagnosis from renal cell carcinoma (RCC) is often challenging because of its epithelioid morphology. Herein is reported three cases of eAMLoma, involving one in a 28-year-old man with TSC and two in women without TSC (34 and 62 years of age, respectively). The male TSC patient had microscopic conventional AMLomas in the same kidney. All patients were positive for melanoma (reactive with HMB45 antibody, and positive for melan A, tyrosinase and microphthalmia transcription factor) and smooth muscle markers (positive for alpha-smooth muscle-specific actin), but not for epithelial markers (cytokeratin, epithelial membrane antigen). In particular, the translocation RCC is an important differential diagnostic candidate, in terms of the positive reaction with HMB45 and morphological similarity. The present tumor samples did not show any reactivity for transcription factor binding to IGHM enhancer 3 or transcription factor EB, which excluded the possibility of translocation RCC. The possibility of eAMLoma should be evaluated as a diagnostic candidate, especially in cases of renal tumors (i) in young patients; (ii) associated with TSC; or (iii) with an epithelioid morphology and a high nuclear grade.

  20. Comparison of combined hormonal vaginal ring with ultralow-dose combined oral contraceptive pills in the management of heavy menstrual bleeding: A pilot study.

    PubMed

    Agarwal, N; Gupta, M; Kriplani, A; Bhatla, N; Singh, N

    2016-01-01

    The aim of this study was to compare combined hormonal vaginal ring with ultralow-dose combined oral contraceptive (COC) pills in management of heavy menstrual bleeding (HMB). Fifty patients were randomised into Group I: vaginal ring (n = 25) and group II: COC pills (n = 25). Menstrual blood loss (MBL) was assessed at baseline, 1, 3 and 6 months (while on treatment) and at 9 months (3 months after stopping therapy). There was significant reduction in baseline pictorial blood loss assessment chart (PBAC) score from 440 ± 188 (Mean ± SD) to 178 ± 95, 139 ± 117, 112 ± 84 and 120 ± 108 in group I and from 452 ± 206 to 204 ± 152, 179 ± 125, 176 ± 164 and 202 ± 167 in group II at 1, 3, 6 and 9 months, respectively (p = 0.001). Reduction in MBL was 72% and 62% at 6 months and up to 71% and 55% at 9 months in group I and group II, respectively (p = 0.001). Reduction in MBL with ring was greater at higher baseline PBAC score but lesser in patients with fibroid > 2 cm. Combined vaginal hormonal treatment for HMB is as effective as oral hormonal therapy, with minor and transient side effects and persistence of response after cessation of therapy.

  1. Effect of 4-hydroxy-2-nonenal on myoglobin-mediated lipid oxidation when varying histidine content and hemin affinity.

    PubMed

    Grunwald, Eric W; Tatiyaborworntham, Nantawat; Faustman, Cameron; Richards, Mark P

    2017-07-15

    The compound 4-hydroxy-2-nonenal (HNE) dissolved in water was examined to remove potential effects of using ethanol to solubilize the aldehyde such as altering protein structure or redox properties of myoglobin (Mb). HNE became covalently bound to sperm whale Mb at up to five sites based on ESI-MS analysis. Adducted Mb promoted lipid oxidation in washed muscle more effectively than non-adducted Mb. Alkylation of P88H/Q152HMb with HNE accelerated metMb formation and subsequent lipid oxidation. P88H/Q152HMb exposed to HNE enhanced lipid oxidation compared to wild-type Mb exposed to HNE. Results using H97A Mb suggested that the combination of HNE and low hemin affinity facilitated rapid decomposition of preformed lipid hydroperoxides to secondary lipid oxidation products. HNE and HHE (4-hydroxy-2-hexenal) facilitated Mb-mediated lipid oxidation similarly. The potential mechanisms by which Mb binding of α,β-unsaturated aldehydes affect Mb oxidation and the onset of lipid oxidation are discussed.

  2. S-100 Negative Granular Cell Tumor (So-called Primitive Polypoid Non-neural Granular Cell Tumor) of the Oral Cavity.

    PubMed

    Rawal, Yeshwant B; Dodson, Thomas B

    2016-10-05

    Four cases of cutaneous S-100 negative granular cell tumor were described in 1991. Until now, only 3 cases of oral involvement have been documented in English literature. Two additional cases of oral S-100 negative granular cell tumor are described. Immunohistochemical markers were applied to exclude other lesions that may show the presence of granular cells. The clinical findings were correlated with the histopathological and immunohistochemical features to arrive at the appropriate diagnosis. S-100 negative granular cell tumors are erythematous polypoid masses commonly mistaken for granulation tissue or a pyogenic granuloma. Any part of the oral cavity may be affected. Histopathologically, the lesions consist of sheets, nests, and fascicles of granular cells that are S-100 negative. The granular cells are non-reactive to SMA, HMB45, Melan A, and CD163. The intracytoplasmic granules are diffusely and strongly positive to NKI/C3. The cell lineage of the S-100 negative granular cell tumor is obscure. Absence of staining with CD163 excludes a histiocytic lineage. Absence of staining with S-100 excludes a neural origin. Absence of staining with S-100 and key melanoma markers HMB45 and Melan A also excludes a melanocytic origin. In this context, positive reactivity with NKI/C3 is indicative of presence of intracytoplasmic lysosomal granules only. Greater awareness of this lesion in the oral cavity will result in better characterization of its biologic potential.

  3. Differentiating intratumoral melanocytes from Langerhans cells in nonmelanocytic pigmented skin tumors in vivo by label-free third-harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Weng, Wei-Hung; Liao, Yi-Hua; Tsai, Ming-Rung; Wei, Ming-Liang; Huang, Hsin-Yi; Sun, Chi-Kuang

    2016-07-01

    Morphology and distribution of melanocytes are critical imaging information for the diagnosis of melanocytic lesions. However, how to image intratumoral melanocytes noninvasively in pigmented skin tumors is seldom investigated. Third-harmonic generation (THG) is shown to be enhanced by melanin, whereas high accuracy has been demonstrated using THG microscopy for in vivo differential diagnosis of nonmelanocytic pigmented skin tumors. It is thus desirable to investigate if label-free THG microscopy was capable to in vivo identify intratumoral melanocytes. In this study, histopathological correlations of label-free THG images with the immunohistochemical images stained with human melanoma black (HMB)-45 and cluster of differentiation 1a (CD1a) were made. The correlation results indicated that the intratumoral THG-bright dendritic-cell-like signals were endogenously derived from melanocytes rather than Langerhans cells (LCs). The consistency between THG-bright dendritic-cell-like signals and HMB-45 melanocyte staining showed a kappa coefficient of 0.807, 84.6% sensitivity, and 95% specificity. In contrast, a kappa coefficient of -0.37, 21.7% sensitivity, and 30% specificity were noted between the THG-bright dendritic-cell-like signals and CD1a staining for LCs. Our study indicates the capability of noninvasive label-free THG microscopy to differentiate intratumoral melanocytes from LCs, which is not feasible in previous in vivo label-free clinical-imaging modalities.

  4. Minute perivascular epithelioid cell (PEC) nests in the abdominal lymph nodes--a putative precursor of PEComa.

    PubMed

    Nagasaka, Toru; Murakami, Yoshiko; Sasaki, Eiichi; Hosoda, Waki; Nakanishi, Toru; Yatabe, Yasushi

    2015-04-01

    A perivascular epithelioid cell tumor (PEComa) is a peculiar growth defined as a mesenchymal tumor composed of histologically and immunohistochemically distinct perivascular epithelioid cells (PECs). Because neither normal counterparts nor precursor lesions of PEComa have been identified, we examined minute PEC nests, ranged from 0.8 mm to 10 mm, to investigate the possible origin of the PEComa. We examined a total of 80 677 para-aortic and pelvic lymph nodes that were systematically dissected from 1656 patients for gynecological malignancies. The identified lesions were confirmed immunohistochemically with multiple PEC markers, including smooth muscle actin, HMB45, melan-A, MiTF, ER and PgR. A total of 66 minute PEC nests were found in 21 patients (1.3% of the total population) with an average frequency of 3.1 lesions per patient. In cases of multiple involvement, 11 of 13 nests were located at the same level of multiple lymph node or on continuous levels. The lesions were preferentially distributed at the level of para-aortic and high pelvic lymph nodes. All nests were positive for actin and HMB45, whereas the other markers were positive with varying frequencies. The minute PEC nests may be associated with the possible normal counterpart of PEComas. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  5. Microbial-mammalian co-metabolites dominate the age-associated urinary metabolic phenotype in Taiwanese and American Populations

    PubMed Central

    Swann, Jonathan R.; Spagou, Konstantina; Lewis, Matthew; Nicholson, Jeremy K.; Glei, Dana A.; Seeman, Teresa E.; Coe, Christopher L.; Goldman, Noreen; Ryff, Carol D.; Weinstein, Maxine; Holmes, Elaine

    2013-01-01

    Understanding the metabolic processes associated with aging is key to developing effective management and treatment strategies for age-related diseases. We investigated the metabolic profiles associated with age in a Taiwanese and an American population. 1H NMR spectral profiles were generated for urine specimens collected from the Taiwanese Social Environment and Biomarkers of Aging Study (SEBAS; n= 857; age 54-91 years) and the Mid-Life in the USA study (MIDUS II; n= 1148; age 35-86 years). Multivariate and univariate linear projection methods revealed some common age-related characteristics in urinary metabolite profiles in the American and Taiwanese populations, as well as some distinctive features. In both cases, two metabolites--4-cresyl sulfate (4CS) and phenylacetylglutamine (PAG)—were positively associated with age. In addition, creatine and β-hydroxy-β-methylbutyrate (HMB) were negatively correlated with age in both populations (p<4×10-6). These age-associated gradients in creatine and HMB reflect decreasing muscle mass with age. The systematic increase in PAG and 4CS was confirmed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Both are products of concerted microbial-mammalian host co-metabolism and indicate an age-related association with the balance of host-microbiome metabolism. PMID:23701591

  6. Recent advances in managing and understanding menstrual disorders

    PubMed Central

    Ali, Moazzam

    2015-01-01

    Menstrual disorders are a major reason for gynaecological consultations worldwide and, unfortunately there are many different definitions and classifications of this condition. Clear definitions and terminology are necessary for scientific literature, particularly for clinicians, and for clinical trials comparing two treatments. The International Federation of Gynaecology and Obstetrics (FIGO) Menstrual Disorders Working Group has proposed abandoning the use of one common term, dysfunctional uterine bleeding (DUB), while continuing to use the terms abnormal uterine bleeding (AUB) and heavy menstrual bleeding (HMB). Furthermore, the group issued the PALM-COEIN classification system for menstrual disorders, which has quickly been adopted around the world. The PALM-COEIN system allows clinicians and researchers to identify and classify women with both AUB and HMB in a systematic manner, provides reliable information for research purposes and for epidemiological and prevalence studies in different settings, and supports accurate diagnoses and treatment. Additionally, this classification system is useful for selecting treatments appropriate for different stages of women's reproductive years and for different patterns of menstrual bleeding. Among the proposed treatments are the use of combined oral contraceptives, the levonorgestrel-releasing intrauterine system, tranexamic acid, mefenamic acid, and other nonsteroidal anti-inflammatory drugs (NSAIDs). PMID:25926984

  7. Increased Activity and Number of Epidermal Melanocytes in Lesional Psoriatic Skin.

    PubMed

    Abdel-Naser, Mohamed Badawy; Liakou, Aikaterini I; Elewa, Rana; Hippe, Sabine; Knolle, Jürgen; Zouboulis, Christos C

    2016-01-01

    Psoriatic lesions may resolve with hypo- or hyperpigmentation. The involvement of melanocytes in this dichotomous clinical outcome is not fully investigated. Qualitative and quantitative assessment of melanocytes in untreated lesional and non-lesional psoriatic skin (n = 15) and healthy controls (n = 10). Skin biopsies were labelled immunohistochemically (APAAP technique) with the antimelanocyte monoclonal antibodies (MoAbs) HMB45, Melan A, tyrosinase and microphthalmia-associated transcription factor (MITF). The labelled melanocytes were evaluated by an independent investigator with a digital image analyser. Lesional melanocytes, in contrast to those in non-lesional and healthy skin, exhibited features of activation in the form of dilatation, prominent and long dendrites and intense labelling. The number of melanocytes was significantly increased in psoriatic lesions in comparison with non-lesional psoriatic and healthy skin as shown by counts of cells labelled with the MoAbs HMB45 (3-fold; p < 0.001), Melan A (1.6-fold; p < 0.01) and tyrosinase (1.5-fold; p < 0.01). In contrast, labelling with MITF revealed no significant difference (1.2-fold increase; p > 0.05). Likewise, no significant difference between non-lesional psoriatic and healthy skin control was found (p > 0.05). Furthermore, no positively labelled dermal cells were detected, apart from few only detected with Melan A. Epidermal melanocyte activity and numbers are increased in the epidermal compartment of psoriatic lesions providing an explanation for postinflammatory hyperpigmentation. © 2016 S. Karger AG, Basel.

  8. Expression of basement membrane antigens in spindle cell melanoma.

    PubMed

    Prieto, V G; Woodruff, J M

    1998-07-01

    Spindle cell melanoma (SCM) is an uncommon form of melanoma that may be confused histologically with other tumors, including malignant peripheral nerve sheath tumors (MPNST). Tumors with neural differentiation and melanocytic nevi may both show basement membrane immunohistochemically and at the ultrastructural level. However, most ultrastructural studies of melanoma have failed to demonstrate well formed basement membrane around tumor cells. The presence of basement membrane has been used by some authors as evidence favoring MPNST, as opposed to SCM. To evaluate this distinction immunohistochemically, 22 primary and metastatic cutaneous melanomas having a spindle cell component (SCM) were studied using monoclonal antibodies against laminin and Type IV collagen. S100 protein and HMB45 antigen expression were also studied. All but one of the SCM were reactive for S100 protein in at least 25% of the cells. Thirteen of 20 tumors (65%) were focally reactive with HMB45. Laminin was expressed in 42% of the tumors (only membranous pattern in 3; cytoplasmic and membranous in 5). Seventeen tumors (77%) expressed type IV collagen (only membranous pattern in 7; cytoplasmic and membranous pattern in 10). Laminin and type IV collagen, known components of basement membrane, are often found in SCM. Therefore, their detection cannot be used to distinguish SCM from MPNST.

  9. Melanosis of the vagina and human papillomavirus infection, an uncommon pathology: case report.

    PubMed

    Núñez-Troconis, José; Delgado, Mariela; González, Gerardo; Rivas, Airiaudis; Molero, Katherine

    2011-09-01

    Benign melanotic lesions of the vagina are uncommon and only a few cases have been reported in the literature. A 34-year-old woman was referred because of a Vaginal Intraepithelial Neoplasia 1 biopsy result. On the gynecological examination, two different hyperpigmented areas were noted in the vagina. The colposcopic visualization of the cervix and vagina found an aceto-white lesion at the right lateral wall of the upper third of the vagina. Biopsies from three areas were taken. Histological study reported a melanosis of the vagina and HPV infection. An immunohistochemical panel of epithelial markers was performed in vaginal samples, such as Cytokeratin AE1/AE3 and epithelial membrane antigen, mesenchymal marker: vimentin; melanocytic makers: protein S-100 and HMB45 (Human Melanoma Black); proliferating cell marker: proliferating cell nuclear antigen (PCNA), and P-53 oncoprotein. High Risk (16, 18, 31, 45) and Low Risk (6, 11) HPV types were studied by In Situ Hybridization using the same vaginal samples. CK, EMA and Vimentin were 2+. Melanocytic markers, HMB45 and S100, and PCNA were 1+ in basal cell layer. P-53 was negative. The melanotic tissue and acetowhite lesion were positives to HPV Types 6,11. In conclusion, melanosis of the vagina is a uncommon benign pathology. Usually, melanosis is present in women over 40 years old. We present a case of melanosis of the vagina in a young woman infected with low-risk HPV types and review the literature.

  10. Synthesis of peptide analogues using the multipin peptide synthesis method.

    PubMed

    Valerio, R M; Benstead, M; Bray, A M; Campbell, R A; Maeji, N J

    1991-08-15

    Modification of the multipin peptide synthesis method which allows the simultaneous synthesis of large numbers of different peptide analogues is described. Peptides were assembled on polyethylene pins derivatized with a 4-(beta-alanyloxymethyl)benzoate (beta-Ala-HMB) handle. For comparative purposes, peptides were also assembled on the diketopiperazine-forming handle N epsilon-(beta-alanyl)lysylprolyloxylactate. In model studies it was demonstrated that beta-Ala-HMB-linked peptides were cleaved from polyethylene pins with dilute sodium hydroxide or 4% methylamine/water to yield analogues with beta-Ala-free acid (beta-Ala-CO2H) and beta-Ala-methylamide (beta-Ala-CONHCH3), respectively. To assess the suitability of this approach for T-cell determinant analysis, analogues of a known T-cell determinant were synthesized with the various C-terminal endings. Peptides were characterized by amino acid analysis and fast atom bombardment-mass spectrometry. HPLC of the crude cleaved peptides indicated that 22 of the 24 peptides were greater than 95% pure. These crude peptide solutions were nontoxic in sensitive cell culture assays without further purification. All three cleavage procedures gave comparable activities in T-cell proliferation assays. These results demonstrate the potential of the multipin peptide synthesis method for the production of large numbers of different peptide analogues.

  11. Microbial-mammalian cometabolites dominate the age-associated urinary metabolic phenotype in Taiwanese and American populations.

    PubMed

    Swann, Jonathan R; Spagou, Konstantina; Lewis, Matthew; Nicholson, Jeremy K; Glei, Dana A; Seeman, Teresa E; Coe, Christopher L; Goldman, Noreen; Ryff, Carol D; Weinstein, Maxine; Holmes, Elaine

    2013-07-05

    Understanding the metabolic processes associated with aging is key to developing effective management and treatment strategies for age-related diseases. We investigated the metabolic profiles associated with age in a Taiwanese and an American population. ¹H NMR spectral profiles were generated for urine specimens collected from the Taiwanese Social Environment and Biomarkers of Aging Study (SEBAS; n = 857; age 54-91 years) and the Mid-Life in the USA study (MIDUS II; n = 1148; age 35-86 years). Multivariate and univariate linear projection methods revealed some common age-related characteristics in urinary metabolite profiles in the American and Taiwanese populations, as well as some distinctive features. In both cases, two metabolites--4-cresyl sulfate (4CS) and phenylacetylglutamine (PAG)--were positively associated with age. In addition, creatine and β-hydroxy-β-methylbutyrate (HMB) were negatively correlated with age in both populations (p < 4 × 10⁻⁶). These age-associated gradients in creatine and HMB reflect decreasing muscle mass with age. The systematic increase in PAG and 4CS was confirmed using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). Both are products of concerted microbial-mammalian host cometabolism and indicate an age-related association with the balance of host-microbiome metabolism.

  12. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding.

    PubMed

    Lethaby, Anne; Hussain, Munawar; Rishworth, Josephine R; Rees, Margaret C

    2015-04-30

    Heavy menstrual bleeding (HMB) is an important cause of ill health in women and it accounts for 12% of all gynaecology referrals in the UK. Heavy menstrual bleeding is clinically defined as greater than or equal to 80 mL of blood loss per menstrual cycle. However, women may complain of excessive bleeding when their blood loss is less than 80 mL. Hysterectomy is often used to treat women with this complaint but medical therapy may be a successful alternative.The intrauterine device was originally developed as a contraceptive but the addition of progestogens to these devices resulted in a large reduction in menstrual blood loss. Case studies of two types of progesterone or progestogen-releasing systems, Progestasert and Mirena, reported reductions of up to 90% and improvements in dysmenorrhoea (pain or cramps during menstruation). Insertion, however, may be regarded as invasive by some women, which affects its acceptability as a treatment. Frequent intermenstrual bleeding and spotting is also likely during the first few months after commencing treatment. To determine the effectiveness, acceptability and safety of progesterone or progestogen-releasing intrauterine devices in achieving a reduction in heavy menstrual bleeding. All randomised controlled trials of progesterone or progestogen-releasing intrauterine devices for the treatment of heavy menstrual bleeding were obtained by electronic searches of The Cochrane Library, the specialised register of MDSG, MEDLINE (1966 to January 2015), EMBASE (1980 to January 2015), CINAHL (inception to December 2014) and PsycINFO (inception to January 2015). Additional searches were undertaken for grey literature and for unpublished trials in trial registers. Companies producing progestogen-releasing intrauterine devices and experts in the field were contacted for information on published and unpublished trials. Randomised controlled trials in women of reproductive age treated with progesterone or progestogen

  13. Effects of glutamine on wound healing.

    PubMed

    Kesici, Ugur; Kesici, Sevgi; Ulusoy, Hulya; Yucesan, Fulya; Turkmen, Aygen U; Besir, Ahmet; Tuna, Verda

    2015-06-01

    Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 < 0·001). We conclude that in adults who eat healthy food, who do not have any factor that can affect wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing.

  14. Low-dose dexamethasone as a treatment for women with heavy menstrual bleeding: protocol for response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM)

    PubMed Central

    Warner, P; Weir, C J; Hansen, C H; Douglas, A; Madhra, M; Hillier, S G; Saunders, P T K; Iredale, J P; Semple, S; Walker, B R; Critchley, H O D

    2015-01-01

    Introduction Heavy menstrual bleeding (HMB) diminishes individual quality-of-life and poses substantial societal burden. In HMB endometrium, inactivation of cortisol (by enzyme 11β hydroxysteroid dehydrogenase type 2 (11βHSD2)), may cause local endometrial glucocorticoid deficiency and hence increased angiogenesis and impaired vasoconstriction. We propose that ‘rescue’ of luteal phase endometrial glucocorticoid deficiency could reduce menstrual bleeding. Methods and analysis DexFEM is a double-blind response-adaptive parallel-group placebo-controlled trial in women with HMB (108 to be randomised), with active treatment the potent oral synthetic glucocorticoid dexamethasone, which is relatively resistant to 11βHSD2 inactivation. Participants will be aged over 18 years, with mean measured menstrual blood loss (MBL) for two screening cycles ≥50 mL. The primary outcome is reduction in MBL from screening. Secondary end points are questionnaire assessments of treatment effect and acceptability. Treatment will be for 5 days in the mid-luteal phases of three treatment menstrual cycles. Six doses of low-dose dexamethasone (ranging from 0.2 to 0.9 mg twice daily) will be compared with placebo, to ascertain optimal dose, and whether this has advantage over placebo. Statistical efficiency is maximised by allowing randomisation probabilities to ‘adapt’ at five points during enrolment phase, based on the response data available so far, to favour doses expected to provide greatest additional information on the dose–response. Bayesian Normal Dynamic Linear Modelling, with baseline MBL included as covariate, will determine optimal dose (re reduction in MBL). Secondary end points will be analysed using generalised dynamic linear models. For each dose for all end points, a 95% credible interval will be calculated for effect versus placebo. Ethics and dissemination Dexamethasone is widely used and hence well-characterised safety-wise. Ethical approval has been

  15. Lymphangioma of the small bowel mesentery: a case report and review of the literature.

    PubMed

    Suthiwartnarueput, Worapop; Kiatipunsodsai, Siriphut; Kwankua, Amolchaya; Chaumrattanakul, Utairat

    2012-11-21

    Lymphangioma is a rare benign condition characterized by proliferation of lymphatic spaces. It is usually found in the head and neck of affected children. Lymphangioma of the small-bowel mesentery is rare, having been reported for less than 1% of all lymphangiomas. Importantly, it can cause fatal complications such as volvulus or involvement of the main branch of the mesenteric arteries, requiring emergency surgery. Moreover, the gross and histopathologic findings may resemble benign multicystic mesothelioma and lymphangiomyoma. Immunohistochemical study for factor VIII-related antigen, D2-40, calretinin and human melanoma black-45 (HMB-45) are essential for diagnosis. Factor VIII-related antigen and D2-40 are positive in lymphangioma but negative in benign multicystic mesothelioma. HMB-45 shows positive study in the smooth-muscle cells around the lymphatic spaces of the lymphangiomyoma. We report a case of small-bowel volvulus induced by mesenteric lymphangioma in a 2-year-and-9-mo-old boy who presented with rapid abdominal distension and vomiting. The abdominal computed tomography scan showed a multiseptated mass at the right lower quadrant with a whirl-like small-bowel dilatation, suggestive of a mesenteric cyst with midgut volvulus. The intraoperative findings revealed a huge, lobulated, yellowish pink, cystic mass measuring 20 cm × 20 cm × 10 cm, that was originated from the small bowel mesentery with small-bowel volvulus and small-bowel dilatation. Cut surface of the mass revealed multicystic spaces containing a milky white fluid. The patient underwent tumor removal with small-bowel resection and end-to-end anastomosis. Microscopic examination revealed that the cystic walls were lined with flat endothelial cells and comprised of smooth muscle in the walls. The flat endothelial cells were positive for factor VIII-related antigen and D2-40 but negative for calretinin. HMB-45 showed negative study in the smooth-muscle cells around the lymphatic spaces. Thus

  16. Management of abnormal uterine bleeding in low- and high-resource settings: consideration of cultural issues.

    PubMed

    Haththotuwa, Rohana; Goonewardene, Malik; Desai, Shyam; Senanayake, Lakshman; Tank, Jaydeep; Fraser, Ian S

    2011-09-01

    In non industrialized countries the incidence of heavy menstrual bleeding (HMB) appears to be similar to that of industrialized countries, although data is scanty. In low-resource settings, women with abnormal uterine bleeding (AUB) often delay seeking medical care because of cultural beliefs that a heavy red menstrual bleed is healthy. Efforts to modify cultural issues are being considered. A detailed history and a meticulous examination are the important foundations of a definitive diagnosis and management in low-resource settings but are subject to time constraints and skill levels of the small numbers of health professionals. Women's subjective assessment of blood loss should be combined, if possible, with a colorimetric hemoglobin assessment, if full blood count is not possible. Outpatient endometrial sampling, transvaginal sonography, and hysteroscopy are available in some non industrialized countries but not in the lowest resource settings. After exclusion of serious underlying pathology, hematinics should be commenced and antifibrinolytic or nonsteroidal anti-inflammatory drugs considered during menses to control the bleeding. Intrauterine or oral progestogens or the combined oral contraceptive are often the most cost-effective long-term medical treatments. When medical treatment is inappropriate or has failed, the surgical options available most often are myomectomy or hysterectomy. Hysteroscopic endometrial resection or newer endometrial ablation procedures are available in some centers. If hysterectomy is indicated the vaginal route is the most appropriate in most low-resource settings. In low-resource settings, lack of resources of all types can lead to empirical treatments or reliance on the unproven therapies of traditional healers. The shortage of human resources is often compounded by a limited availability of operative time. Governments and specialist medical organizations have rarely included attention to AUB and HMB in their health programs

  17. Primary mandibular xanthoma: case report.

    PubMed

    de Araujo, Melissa Rodrigues; Scariot, Rafaela; Uetanabaro, Lucas; Luvison Gomes da Silva, Larissa; Giovanini, Allan Fernando

    2015-10-01

    Xanthoma is a very rare bone tumor, especially in the mandible, that can be associated with metabolic diseases such as hyperlipidemia. A 14-year-old girl presented with a non-corticated unilocular radiolucent lesion observed on panoramic radiography. The lesion was located between the roots of the left first and second premolar teeth, extending from the cervical to the apical region, measuring approximately 1 cm in greatest dimension. An excisional biopsy revealed foam cells and occasional nonfoamy mononuclear macrophage-like cells spread among a discrete fibrous stroma. Immunohistochemically, the xanthomatous cells were CD68 and vimentin positive, focally positive for S100, CD1a, and CD3 and negative for AE1/AE3, CD20, CD117, and HMB45. Hematologic and biochemical investigations ruled out systemic disease.

  18. Primary anorectal malignant melanoma: an uncommon anorectal pathology.

    PubMed

    Juanmartiñena Fernández, José Francisco; Fernández-Urien, Ignacio; Córdoba, Alicia

    2016-09-01

    Anorectal malignant melanoma (AMM) is most common primary melanoma of gastrointestinal tract, accounting for 0.05% and 1% of all colorectal and anal cancers. We reported an 85 year-old woman with no significant past medical history who presented two-month period of rectal bleeding, abdominal pain, tenesmus and 2kg weight-loss. Laboratory markers were unremarkable, although rectal examination revealed two small haemorrhoids and a firm, non-obstructing mass in the lower rectum. Colonoscopy confirmed presence of an ulcerated pigmented neoplasm arising at dental line [A,B]. No distant metastases were found on computed tomography [C] although presented metastatic regional lymph nodes on pelvic MRI [D]. Therefore, abdominoperineal resection was performed, confirming loco-regional disease. Histopathology showed malignant melanoma with positive stains in immunohistochemistry for protein S100, HMB-45 and Melan-A [E,F,G,H] and stained negative for c-Kit.

  19. Angiomyolipome épithélioïde rénal mimant un carcinome rénal

    PubMed Central

    Bouaziz, Hanen; Khiari, Ramzi; Dridi, Mohamed; Ghozzi, Samir; Rais, Nawfel Ben

    2016-01-01

    L'angiomyolipome épithélioide est une forme rare d'angiomyolipome à potentiel malin, considéré récemment par l'OMS comme une entité à part dans la classification des tumeurs rénales. Cette lésion pose un problème dans le diagnostic différentiel avec les carcinomes à cellules claires. Il n'y a pas de critère spécifique clinique ou radiologique caractérisant cette tumeur. L'immunohistochimie en révélant la positivité des cellules épithélioide au marqueur HMB45 est essentielle au diagnostic. Le traitement doit être discuté en concertation pluridisciplinaire. PMID:27642438

  20. Signet ring cell melanocytic nevus: report of a case over trichilemmal cyst and review of the literature.

    PubMed

    Sabater Marco, Vicente; Escutia Muñoz, Begoña; Morera Faet, Arturo; Botella Estrada, Rafael

    2012-02-01

    Different melanocytic nevi have been reported as being associated with dermal cysts. Signet ring cell melanocytic nevus is a rare variant of melanocytic nevus characterized by cells with signet ring morphology within a common melanocytic nevus. This article describes an exceptional case of melanocytic nevus composed exclusively of signet ring cells over a trichilemmal cyst. Histologically, above the cyst, there was a small, symmetrical and sharply demarcated lesion showing a compound proliferation of small, round, monomorphous cells with signet ring morphology. Immunohistochemically, signet ring cells were negative for cytokeratin AE1/3, leukocyte common antigen, HMB-45, and CD34. Occasionally, isolated signet ring cells were positive for S-100 and melan A. Melanocytic nevus composed of signet ring cells should raise the differential diagnosis with other cutaneous tumors exhibiting signet ring cells. Previous cases of this entity reported in the literature are also reviewed.

  1. Ruptured pericardial perivascular epithelioid cell tumor (PEComa) leading to sudden death: an autopsy case report and review of the literature.

    PubMed

    Zhang, Lingxin; Carpenter, Danielle; Dehner, Louis P

    2016-01-01

    A 30-year-old man with past medical history of atrial fibrillation/flutter passed away after presenting with sudden-onset cardiac dysfunction. The postmortem examination revealed cardiac tamponade secondary to rupture of a 7.2-cm pericardial perivascular epithelioid cell tumor (PEComa). The tumor grossly appeared to arise from the transverse pericardial sinus and focally penetrated the epicardium of the right atrium. Microscopically, it was composed of predominately spindle cells with low nuclear grade, no pleomorphism, or readily apparent mitoses. Immunohistochemistry revealed cytoplasmic reactivity for HMB-45, desmin, and smooth muscle actin. Electron microscopic findings were characterized by melanosome-like structures intermixed with intermediate filaments and abundant stacked endoplasmic reticulum. The present case is unique among previously reported pericardial/myocardial PEComas as a first example resulting in unexpected cardiac tamponade and sudden cardiac death. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Hepatic perivascular epithelioid cell tumor (PEComa): a case report with a review of literatures

    PubMed Central

    Son, Hyun-Jin; Kang, Dong Wook; Kim, Joo Heon; Han, Hyun Young; Lee, Min Koo

    2017-01-01

    Hepatic perivascular epithelioid cell tumors (PEComas) are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45) and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA). PMID:28288506

  3. Melanotic neuroectodermal tumor of infancy arising in the temporal bone.

    PubMed

    Zhang, Jian-guo; Zhao, Rui-jiao; Kong, Ling-fei

    2015-04-01

    Melanotic neuroectodermal tumor of infancy is a rare melanin-containing neoplasm with locally aggressive and rapid expansile growth, usually involving the maxilla, skull, and mandible of early infancy. Radical surgery is critical for a long-term outcome. We present a case of 14-month-old girl with rapid-growing subcutaneous mass arising in the right temporal bone and extending intracranially on computed tomographic scan. Radical surgery was performed. A brownish-black tumor composed of large pigmented epithelioid cells, positive for cytokeratins and HMB-45, and nests of small neuroblast-like cells positive for neuron-specific enolase and synaptophysin, was diagnosed as melanotic neuroectodermal tumor of infancy. The patient remained well without evidence of recurrence for 1 year after surgery. Clinicopathological features, management alternatives and outcome were discussed. © The Author(s) 2013.

  4. Quantitative determination of the human breast milk macronutrients by near-infrared Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Motta, Edlene d. C. M.; Zângaro, Renato A.; Silveira, Landulfo, Jr.

    2012-03-01

    This work proposes the evaluation of the macronutrient constitution of human breast milk based on the spectral information provided by near-infrared Raman spectroscopy. Human breast milk (5 mL) from a subject was collected during the first two weeks of breastfeeding and stocked in -20°C freezer. Raman spectra were measured using a Raman spectrometer (830 nm excitation) coupled to a fiber based Raman probe. Spectra of human milk were dominated by bands of proteins, lipids and carbohydrates in the 600-1800 cm-1 spectral region. Raman spectroscopy revealed differences in the biochemical constitution of human milk depending on the time of breastfeeding startup. This technique could be employed to develop a classification routine for the milk in Human Milk Banking (HMB) depending on the nutritional facts.

  5. Molecular and functional aspects of menstruation in the macaque.

    PubMed

    Brenner, Robert M; Slayden, Ov D

    2012-12-01

    Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

  6. Uterine angioleiomyoma: A rare variant of uterine leiomyoma--A case report and literature review.

    PubMed

    Diwaker, Preeti; Pradhan, Dinesh; Garg, Garima; Bisaria, Dipti; Gogoi, Kamakhya; Mohanty, Sambit K

    2015-01-01

    Uterine angioleiomyoma (AL) is an extremely rare variant of leiomyoma and only 15 cases have been reported till date. Herein we present a case of AL of the uterus in a 39-year-old multiparous female with polymenorrhagia and pain abdomen. A pelvic ultrasonogram showed a large heterogeneously hypoechoic intramural nodule in the posterior myometrium. The patient underwent a total abdominal hysterectomy. Histological examination of the nodule revealed a moderately cellular spindle cell tumor composed of interlacing fascicles of spindle to plump cells swirling around the thick walled vessels. No hypercellularity, pleomorphism, mitotic figures, or necrosis was identified. The spindle to plump cells showed strong and diffuse immunoreactivity for smooth muscle actin, desmin and progesterone receptor, focal and weak positivity for CD10 and estrogen receptor and were negative for CD34 and HMB-45. The Ki-67 labeling index was low (1%). A diagnosis of AL was offered. The patient is on follow up for over 10 months and is asymptomatic.

  7. [Colorectal melanoma: review of two distinct forms of presentation].

    PubMed

    Díaz-Sánchez, Antonio; Lara, Miguel Ángel; Ortega, Patricia; Aramendi, Teresa; González, Carmen; Alberdi, José M; Del Valle, Emilio; Casado, Isabel; Campos, Rocío; Aldeguer, Mercedes

    2011-02-01

    Malignant melanoma of the colon and rectum is an infrequent disease. Primary anorectal melanoma accounts for 0.1-4.6% of all malignant neoplasms of the anal canal. Melanoma metastatic to the colon is symptomatic only in 4.4% of patients with a primary melanoma at another site and most of these tumors are diagnosed postmortem. We report two cases of colorrectal malignant melanoma. The first case concerned a patient with rectal bleeding who was diagnosed with a rectal lesion compatible with melanoma. Abdominoperineal resection was performed due to positivity of the sentinel lymph node. We discuss the utility of sentinel lymph node detection in this kind of tumor. In the second case, we discovered a polyp compatible with metastatic melanoma in the transverse colon in a patient with a previous diagnosis of melanoma. In both surgical specimens, the diagnosis of melanoma was confirmed by positivity for protein S-100, Melan-A and HMB-45.

  8. Multifocal oral melanoacanthoma associated with Addison's disease and hyperthyroidism: a case report.

    PubMed

    Dantas, Thinali Sousa; Nascimento, Isabelly Vidal do; Verde, Maria Elisa Quezado Lima; Alves, Ana Paula Negreiros Nunes; Sousa, Fabrício Bitu; Mota, Mário Rogério Lima

    2017-01-01

    Oral melanoacanthoma is a mucocutaneous, pigmented, rare, benign, and probably reactive lesion. This paper reports for the first time in the literature a case of multifocal oral melanoacanthoma in a patient diagnosed with Addison's disease and concomitant Graves' disease with hyperthyroidism. The patient presented with oral pigmented lesions, which were hypothesized to be mucosal pigmentation associated with Addison's disease. Due to their unusual clinical pattern, these oral lesions were biopsied and diagnosed as oral melanoacanthoma on histopathology and immunohistochemistry for HMB-45. At the moment of this report, the patient was being treated for her systemic conditions, but the lesions had not regressed. Reactive hyperpigmentation of the skin and mucous membranes may be found in Addison's disease and hyperthyroidism. This case reinforces the hypothesis of a reactive nature for oral melanoacanthoma and highlights the need for investigation of endocrine disorders in patients with multifocal oral melanoacanthoma.

  9. Use of nutritional supplements by high school football and volleyball players.

    PubMed

    Mason, M A; Giza, M; Clayton, L; Lonning, J; Wilkerson, R D

    2001-01-01

    The known use of performance enhancing agents by athletes has occurred throughout history. In the 1960s and 1970s steroids and amphetamines were the supplements most often used. Now athletes are turning to supplements that are either natural or stimulate the release of natural hormones. The purpose of this study is to evaluate the prevalence of use of nutritional supplements among high school football and volleyball players. This study surveyed 495 male football players and 407 female volleyball players from 20 high schools in Northwest Iowa. These athletes completed anonymous surveys and returned them to their coaches. Results showed that 8% of the male athletes and 2% of the female athletes were using supplementation. Supplements used included creatine, androstiendione, HMB, amino acids, DHEA, phosphogen, weight gainer 1850, Tribulus, muscle plus, multivitamins, calcium, GABA, and Shaklee Vita Lea and Physique.

  10. Subungual Acral Fibromyxoma Involving the Bone: A Mimicker of Malignancy.

    PubMed

    Carranza, Carmen; Molina-Ruiz, Ana María; Pérez de la Fuente, Teresa; Kutzner, Heinz; Requena, Luis; Santonja, Carlos

    2015-07-01

    Superficial acral fibromyxoma (SAF) is a recently recognized myxoid tumor that usually occurs on the fingers and toes of middle-aged adults. We report the case of a 53-year-old man with a SAF on the first left toe that had been slowly growing for 2 years. Hispathologically, the lesion was nonencapsulated and was composed of stellate and spindle cells, arranged in a myxoid matrix. No atypia or mitotic figures were found. Neoplastic cells showed positive staining for CD34 and negative staining for epithelial membrane antigen, actin, desmin, keratins, S-100 protein, and HMB45. Main differential diagnoses of SAF include benign and malignant myxoid and spindle cells tumors, such as myxoid fibrous histiocytoma, superficial angiomyxoma, myxoid neurofibroma, myxoid dermatofibrosarcoma protuberans, and low-grade fibromyxoid sarcoma.

  11. Diagnostic utility of epithelial and melanocitic markers with double sequential immunohistochemical staining in differentiating melanoma in situ from invasive melanoma.

    PubMed

    Parra-Medina, Rafael; Morales, Samuel David

    2017-02-01

    Identification of melanoma in situ and its distinction from invasive melanoma is important because of its significant impact on morbidity and mortality. However, this interpretation can cause pitfalls in the diagnosis even with the use of immunohistochemistry. The aim of this study is to evaluate the diagnostic utility of epithelial makers (AE1/AE3, CK5/6, and p63) combined with melanocytic markers (HMB-45, S-100, or Melan-A) using dual-color immunohistochemical staining, performed on a single slide by sequentially applying the antibodies. In this study, we show 4 cases in which examination of routine hematoxylin and eosin slides did not allow for clear-cut distinction between in situ and invasive melanoma and highlight the utility of the double-staining method. Therefore, we recommend this double-staining method with melanocytic and epithelial markers as a helpful adjunct to the diagnosis of cases with a differential diagnosis between in situ and invasive melanoma.

  12. Primary malignant melanoma of uterine cervix with probable origin from benign cervical melanosis

    PubMed Central

    Singh, Nilanchali; Tripathi, Reva; Mala, Yedla Manikya

    2013-01-01

    We report a case of primary malignant melanoma of cervix which is a rare malignancy with only around 60 cases being reported. This patient presented with bleeding per vaginum. A large exophytic growth from cervix with black discolouration was seen. International Federation of Gynaecology and Obsterics (FIGO) staging was stage IIa. Histoimmunocytology confirmed the diagnosis of malignant melanoma of cervix. S-100 and HMB-45 are reliable markers for cervical melanomas. We attempted Wertheim's hysterectomy; but, due to extensive disease, paravescical and pararectal fossae could not be dissected and we had to perform type I hysterectomy. The patient was started on adjuvant chemotherapy with dacarbazine. Despite counselling, she refused a complete course of chemotherapy and died after 6 months. Radical surgery, chemotherapy and immunotherapy are the therapeutic modalities used. In bulky disease, neoadjuvant chemotherapy should be considered to reduce the tumour bulk and facilitate required surgery. Prognosis is poor and unpredictable. PMID:23737592

  13. Controlled radical polymerization of an acrylamide containing L-alanine moiety via ATRP.

    PubMed

    Rafiee, Zahra

    2016-02-01

    Homopolymerization of an optically active acrylamide having an amino acid moiety in the side chain, N-acryloyl-L-alanine (AAla) was carried out via atom transfer radical polymerization (ATRP) at room temperature using 2-hydroxyethyl-2'-methyl-2'-bromopropionate (HMB) or sodium-4-(bromomethyl)benzoate (SBB) as initiator in pure water, methanol/water mixture and pure methanol solvents. The polymerization reaction resulted in the optically active biocompatible amino acid-based homopolymer in good yield with narrow molecular weight distribution. The number average molecular weight increased with conversion and polydispersity was low. The structure and molecular weight of synthesized polymer were characterized by (1)H NMR, FT-IR spectroscopic techniques and size-exclusion chromatography.

  14. Melanocytic Malignant Peripheral Nerve Sheath Tumor of the Male Breast.

    PubMed

    Wang, Haijun; Ge, Jing; Chen, Lirong; Xie, Panpan; Chen, Fangfang; Chen, Yiding

    2009-01-01

    SUMMARY: BACKGROUND: Malignant peripheral nerve sheath tumors are rare tumor entities that originate from peripheral nerve sheaths and have an unfavorable prognosis. Common sites include deeper soft tissues, usually in the proximity of a nerve trunk. Breast is an absolutely rare location of this lesion, and presentation as a breast lump in the male breast is even rarer. CASE REPORT: A 65-year-old man presented with a 6-month history of a painless mass of the left breast. Tissue biopsy was performed. Histopathology revealed a malignant spindle cell tumor which was confirmed to be a melanocytic malignant peripheral nerve sheath tumor on the basis of immunopositivity for HMB45 and S-100. CONCLUSION: There are no generally accepted guidelines for the treatment of malignant peripheral nerve sheath tumors in the male breast. The patient was referred for radiation therapy after simple mastectomy.

  15. Amelanotic Melanoma in the Vicinity of Acquired Melanocytic Nevi and not Arising from Agminated Melanocytic Nevi: Masquerading as Pyogenic Granuloma

    PubMed Central

    Rao, Angoori Gnaneshwar; Babu, V Ashok; Koppada, Divya; Haritha, M; Chandana, P; Swapna; Anoosha

    2016-01-01

    Amelanotic melanoma (AMM) presenting as pyogenic granuloma and occurring in the vicinity of acquired melanocytic nevi is rare. Herein, we report such a manifestation in a 68-year-old male who presented with the painful red nodule and multiple pigmented patches involving the left great toe. Histopathological examination of skin biopsy taken from the nodule with an immunohistochemical study using HMB45 and S-100 confirmed the diagnosis of AMM. Biopsy from the pigmented patch near the nodule showed features of melanocytic nevus. Investigative work up revealed metastatic deposits in the left inguinal lymph node with no evidence of systemic involvement, placing him in malignant melanoma Stage IIIC of American Joint Committee on Cancer (AJCC) tumor node metastasis system. The development of AMM in the vicinity of acquired melanocytic nevi and manifesting as granuloma pyogenicum is unique in this case. PMID:26955141

  16. Nuclear localization of the testis determining gene product SRY

    PubMed Central

    1995-01-01

    We have studied the expression of the human SRY protein (termed p27SRY) in two different cell lines by using specific antibodies. Confocal microscopy enabled us to localize p27SRY precisely in the nucleus in a discrete punctuate pattern. Furthermore, through microinjection experiments, we have demonstrated that the localization of the p27SRY protein into the nucleus was an event involving the NH2-terminal part of the high mobility group (HMG) domain. With the help of several synthetic peptides and various p27SRY mutants, we have characterized a bipartite basic motif in this part of the protein corresponding to a nuclear localization signal. This nuclear localization signal appears to be highly conserved in SRY box- and HMB box-containing proteins, suggesting common properties of nuclear targeting within the HMG box protein family. PMID:7876301

  17. Rapid method for determination of 2-hydroxy-4-(methylthio)butanoic acid in poultry feeds by capillary isotachophoresis.

    PubMed

    Vinjamoori, D V; Schisla, R M

    1986-01-01

    Capillary isotachophoresis, which involves the separation of charged species under an electric field, has been applied to the rapid determination of 2-hydroxy-4-(methylthio)butanoic acid at 0.04-0.50% concentration levels in corn/soy-based poultry feeds, using conductivity detection. The procedure merely involves a 15 min cold water extraction of the sample and a 15 min analysis after injection of the filtrate into the instrument. Since only charged species migrate and non-ionic species stay virtually at the front of the column, extraordinary selectivity can be achieved. The isotachophoresis method is an order of magnitude faster than the gas chromatographic method reported recently and also provides information on HMB-monomer/dimer ratio in the same run. The sample recoveries exceeded 90% in all concentration ranges studied with coefficients of variation less than +/- 10%.

  18. Primary solitary fibrous tumors of liver: a case report and literature review

    PubMed Central

    2013-01-01

    A 42-year-old male presented right upper abdomen pain for more than 6 days, which misdiagnose calculus of intrahepatic duct and acute cholecystitis. An approximately 1.5 cm x 1.0 cm x 1.0 cm nodule was found and resected in left lateral lobe of hepatic. Pathological examination showed spindle cell and fibroblast -like cells within the collagenous stroma. Immunohistochemically, these spindle tumor cells showed diffuse Vim and Bcl-2 positive reactivity, but S-100 protein and HMB45 were negative. The post-operative course was uneventful. Solitary fibrous tumors of the liver, although rare, should be differentiated from mesenchymal lesions of the liver. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4214341041091088. PMID:24294990

  19. Fine-needle aspiration of metastatic melanoma presenting as bilateral breast cysts.

    PubMed

    Inouye, Casey M; Cimino-Mathews, Ashley; Eisner, David; Rosenthal, Dorothy L; VandenBussche, Christopher J

    2017-05-01

    Melanoma is the second most common non-hematopoietic malignancy after carcinomas to metastasize to the breast and often appears as a well-circumscribed, dense nodule on imaging. Although metastatic lesions presenting as bilateral cysts have been reported, this presentation is not common and may mimic benign breast cysts. We present a challenging case of metastatic melanoma presenting as bilateral breast cysts with spindled cytomorphology in a patient with a history of mammary carcinoma. Discordance between the spindled cytomorphology and the morphology of the core biopsy, which was similar to the patient's primary breast cancer, allowed for entertainment of other tumors and disease processes. Confirmatory immunostaining of the cytology material with HMB-45 was important to establish the diagnosis of metastatic melanoma. Diagn. Cytopathol. 2017;45:446-451. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Ureteric Obstruction From Malignant Melanoma in Both Right Double Moiety and Left Single Moiety Ureters.

    PubMed

    March, Brayden; Calopedos, Ross John Spero; Latif, Edward; Ouyang, Rupert

    2017-05-01

    We report the first documented case of malignant melanoma obstructing ureters of both moieties of a duplex kidney and contralateral single moiety ureter in a 51-year-old male. The patient presented with fever, coryzal symptoms, and liver function test derangement several years after 2 superficial spreading melanomas were excised with clear margins. Ultrasonography demonstrated hydronephroureter in both moieties of a complete right-sided duplex kidney. Retrograde pyelograms showed bilateral hydronephroureter and filling defects in all 3 ureters. Biopsied tumor cells were positive for S100, Melan A, and HMB45. Cutaneous melanoma metastasizing to ureters is a rare phenomenon and can present a diagnostic challenge to clinicians if clinically silent. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Epithelioid angiomyolipoma of the liver: a case report

    PubMed Central

    Lee, Soo Yeon; Kim, Baek-hui

    2017-01-01

    Epithelioid angiomyolipoma (EAML) of liver is a rare neoplasm. Hepatic EAML is often misdiagnosed as other neoplasms such as hepatocellular carcinoma due to non-specific clinical and radiologic features. The morphologic features under microscope and immunohistochemistry staining profile are important in the diagnosis EAML. Here, we report a case of 52-year-old man who found 1.2 cm mass in liver by routine checkup. On the impression of hepatocellular carcinoma, lateral sectionectomy of the liver was done. Microscopically, the tumor is composed of predominant epithelioid cells with vascular component and foamy cells. These cells were positive for HMB45, MelanA, and smooth muscle actin and negative for epithelial membrane antigen. The final diagnosis was hepatic EAML. PMID:28301898

  2. CFD and Aeroelastic Analysis of the MEXICO Wind Turbine

    NASA Astrophysics Data System (ADS)

    Carrión, M.; Woodgate, M.; Steijl, R.; Barakos, G.; Gómez-Iradi, S.; Munduate, X.

    2014-12-01

    This paper presents an aerodynamic and aeroelastic analysis of the MEXICO wind turbine, using the compressible HMB solver of Liverpool. The aeroelasticity of the blade, as well as the effect of a low-Mach scheme were studied for the zero-yaw 15m/s wind case and steady- state computations. The wake developed behind the rotor was also extracted and compared with the experimental data, using the compressible solver and a low-Mach scheme. It was found that the loads were not sensitive to the Mach number effects, although the low-Mach scheme improved the wake predictions. The sensitivity of the results to the blade structural properties was also highlighted.

  3. Synthesis and high expression of chitin deacetylase from Colletotrichum lindemuthianum in Pichia pastoris GS115.

    PubMed

    Kang, Lixin; Chen, Xiaomei; Zhai, Chao; Ma, Lixin

    2012-09-01

    A gene, ClCDA, encoding chitin deacetylase from Colletotrichum lindemuthianum, was optimized according to the codon usage bias of Pichia pastoris and synthesized in vitro by overlap extension PCR. It was secretorily expressed in P. pastoris GS115 using the constitutive expression vector pHMB905A. The expression level reached the highest with 110 mg/l culture supernatant after 72 h of methanol induction, which comprised 77.27 U/mg chitin deacetylase activity. SDS-PAGE, mass spectrometry, and deglycosylation assays demonstrated that partial recombinant protein was glycosylated with an apparent molecular mass of 33 kDa. The amino acid sequences of recombinant proteins were confirmed by mass spectrometry.

  4. Preparation and Surface Property of Fluoroalkyl End-Capped Vinyltrimethoxysilane Oligomer/Talc Composite-Encapsulated Organic Compounds: Application for the Separation of Oil and Water.

    PubMed

    Oikawa, Yuri; Saito, Tomoya; Yamada, Satoshi; Sugiya, Masashi; Sawada, Hideo

    2015-07-01

    Fluoroalkyl end-capped vinyltrimethoxysilane oligomer [R(F)-(CH2-CHSi(OMe)3)n-R(F); n = 2, 3; R(F) = CF(CF3)OC3F7 (R(F)-VM oligomer)] can undergo the sol-gel reaction in the presence of talc particles under alkaline conditions at room temperature to provide the corresponding fluorinated oligomeric silica/talc nanocomposites (RF-VM-SiO2/Talc). A variety of guest molecules such as 2-hydroxy-4-methoxybenzophenone (HMB), bisphenol A (BPA), bisphenol AF, 3-(hydroxysilyl)-1-propanesulfonic acid (THSP), and perfluoro-2-methyl-3-oxahexanoic acid (R(F)-COOH) are effectively encapsulated into the R(F)-VM-SiO2/Talc composite cores to afford the corresponding fluorinated nanocomposites-encapsulated these guest molecules. The R(F)-VM-SiO2/Talc composites encapsulated low molecular weight aromatic compounds such as HMB and BPA can exhibit a superoleophilic-superhydrophobic characteristic on the surfaces; however, the R(F)-VM-SiO2/Talc composite-encapsulated THSP and R(F)-COOH exhibit a superoleophobic-superhydrophilic characteristic on the modified surfaces. In these nanocomposites, the R(F)-VM-SiO2/Talc/THSP composites are applicable to the surface modification of polyester fabric, and the modified polyester fabric possessing a superoleophobic-superhydrophilic characteristic on the surface can be used for the membrane for oil (dodecane)/water separation. In addition, the R(F)-VM-SiO2/Talc composites-encapsulated micrometer-size controlled cross-linked polystyrene particles can be also prepared under similar conditions, and the obtained composite white-colored particle powders are applied to the packing material for the column chromatography to separate water-in-oil (W/O) emulsion.

  5. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS)

    PubMed Central

    Cruz-Jentoft, Alfonso J.; Landi, Francesco; Schneider, Stéphane M.; Zúñiga, Clemente; Arai, Hidenori; Boirie, Yves; Chen, Liang-Kung; Fielding, Roger A.; Martin, Finbarr C.; Michel, Jean-Pierre; Sieber, Cornel; Stout, Jeffrey R.; Studenski, Stephanie A.; Vellas, Bruno; Woo, Jean; Zamboni, Mauro; Cederholm, Tommy

    2014-01-01

    Objective: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). Methods: PubMed and Dialog databases were searched (January 2000–October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected. Results: prevalence of sarcopenia was, with regional and age-related variations, 1–29% in community-dwelling populations, 14–33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function. Conclusion: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes. PMID:25241753

  6. Treating sarcopenia in older and oldest old.

    PubMed

    Martone, Anna Maria; Lattanzio, Fabrizia; Abbatecola, Angela Marie; Carpia, Domenico La; Tosato, Matteo; Marzetti, Emanuele; Calvani, Riccardo; Onder, Graziano; Landi, Francesco

    2015-01-01

    The presence of sarcopenia is not only rapidly rising in geriatric clinical practice and research, but is also becoming a significant concept in numerous medical specialties. This rapidly rising concept has encouraged the need to identify methods for treating sarcopenia. Physical activity measures using resistance training exercise, combined with nutritional interventions (protein and amino acid supplementation) have shown to significantly improve muscle mass and strength in older persons. Moreover, resistance training may improve muscle strength and mass by improving protein synthesis in skeletal muscle cells. Aerobic exercise has also shown to hold beneficial impacts on sarcopenia by improving insulin sensitivity. At the moment, the literature indicates that most significant improvement in sarcopenia is based on exercise programs. Thus, this type of intervention should be implemented in a persistent manner over time in elders, with or at risk of muscle loss. At the same time, physical training exercise should include correcting nutritional deficits with supplementation methods. For example, in older sarcopenic patients with adequate renal function, daily protein intake should be increased to >1. 0 grams of protein per kilogram of body weight. In particular, leucine, - hydroxy β-methylbutyrate (HMB), creatine and some milk-based proteins have been shown to improve skeletal muscle protein balance. In addition, it is also recommended for adjustment of for vitamin D deficiency, if present, considering the crucial role of vitamin D in the skeletal muscle. In this review, we provide evidence regarding the effects of different physical exercise protocols, specific nutritional intervention, and some new metabolic agents (HMB, citrulline malate, ornithine, and others) on clinical outcomes related to sarcopenia in older adults.

  7. Morphological and Morphometrical Characterization of Meloidogyne incognita from Different Host Plants in Four Districts of Punjab, India

    PubMed Central

    Kaur, Harpreet; Attri, Rajni

    2013-01-01

    The population of M. incognita, the root knot nematode (RKN) was found infesting five different host plants (okra, banana, sunflower, bottle gourd, and brinjal) out of 24 examined from four districts of Punjab, India (Gurdaspur, Ludhiana, Patiala, and Hoshiarpur). Morphological and morphometrical characterization indicated that in the case of mature female, the characters of body length and width, neck length, ratio ‘a’, anus to tail terminus (ATT), interphasmid distance (IPD), and perineal pattern were recorded as stable characters. These taxonomic characters can be reliable for identification. All characters of second-stage juvenile (J2) such as body length, stylet length, head to median bulb length (H-MB), distance from median bulb to excretory pore (MB-EP), tail length, anal body width (ABW), and ratios C and C’ were highly variable. Analysis of interpopulation morphometric characters of mature female of M. incognita, namely, body length, width, and ratio ‘a’ were moderately variable characters (CV 0.26% to 20%) and stylet length, neck length, length of median bulb (LMB), and width of median bulb (WMB) were highly variable (CV 1.0% to 36.1%). In the perineal pattern, the two characters ATT and IPD were moderately variable (CV 8.8% to 17.6%) and two characters, anus to vulval slit (AVS) and length of vulval slit (LVS), were highly variable (CV 2.1% to 40.5%). In J2, body length, stylet length, H-MB, MB-EP, ABW, tail length, ratios C, and C’ were highly variable characters (CV > 12%). PMID:23833327

  8. Morphological and Morphometrical Characterization of Meloidogyne incognita from Different Host Plants in Four Districts of Punjab, India.

    PubMed

    Kaur, Harpreet; Attri, Rajni

    2013-06-01

    The population of M. incognita, the root knot nematode (RKN) was found infesting five different host plants (okra, banana, sunflower, bottle gourd, and brinjal) out of 24 examined from four districts of Punjab, India (Gurdaspur, Ludhiana, Patiala, and Hoshiarpur). Morphological and morphometrical characterization indicated that in the case of mature female, the characters of body length and width, neck length, ratio 'a', anus to tail terminus (ATT), interphasmid distance (IPD), and perineal pattern were recorded as stable characters. These taxonomic characters can be reliable for identification. All characters of second-stage juvenile (J2) such as body length, stylet length, head to median bulb length (H-MB), distance from median bulb to excretory pore (MB-EP), tail length, anal body width (ABW), and ratios C and C' were highly variable. Analysis of interpopulation morphometric characters of mature female of M. incognita, namely, body length, width, and ratio 'a' were moderately variable characters (CV 0.26% to 20%) and stylet length, neck length, length of median bulb (LMB), and width of median bulb (WMB) were highly variable (CV 1.0% to 36.1%). In the perineal pattern, the two characters ATT and IPD were moderately variable (CV 8.8% to 17.6%) and two characters, anus to vulval slit (AVS) and length of vulval slit (LVS), were highly variable (CV 2.1% to 40.5%). In J2, body length, stylet length, H-MB, MB-EP, ABW, tail length, ratios C, and C' were highly variable characters (CV > 12%).

  9. Photochemical Oxidation of a Manganese(III) Complex with Oxygen and Toluene Derivatives to Form a Manganese(V)-Oxo Complex

    PubMed Central

    Jung, Jieun; Ohkubo, Kei; Prokop-Prigge, Katharine A.; Neu, Heather M.; Goldberg, David P.; Fukuzumi, Shunichi

    2013-01-01

    Visible light photoirradiation of an oxygen-saturated benzonitrile solution of a manganese(III) corrolazine complex [(TBP8Cz)MnIII (1): [TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato3−] in the presence of toluene derivatives resulted in formation of the manganese(V)-oxo complex [(TBP8Cz)MnV(O)]. The photochemical oxidation of (TBP8Cz)MnIII with O2 and hexamethylbenzene (HMB) led to the isosbestic conversion of 1 to (TBP8Cz)MnV(O), accompanied by the selective oxidation of HMB to pentamethylbenzyl alcohol (87%). The formation rate of (TBP8Cz)MnV(O) increased with methyl group substitution, from toluene, p-xylene, mesitylene, durene, pentamethylbenzene, up to hexamethylbenzene. Deuterium kinetic isotope effects (KIEs) were observed for toluene (KIE = 5.4) and mesitylene (KIE = 5.3). Femtosecond laser flash photolysis of (TBP8Cz)MnIII revealed the formation of a tripquintet excited state, which was rapidly converted to a tripseptet excited state. The tripseptet excited state was shown to be the key, activated state that reacts with O2 via a diffusion-limited rate constant. The data allow for a mechanism to be proposed in which the tripseptet excited state reacts with O2 to give the putative (TBP8Cz)MnIV(O2•−), which then abstracts a hydrogen atom from the toluene derivatives in the rate-determining step. The mechanism of hydrogen abstraction is discussed by comparison of the reactivity with the hydrogen abstraction from the same toluene derivatives by cumylperoxyl radical. Taken together, the data suggest a new catalytic method is accessible for the selective oxidation of C-H bonds with O2 and light, and the first evidence for catalytic oxidation of C–H bonds was obtained with 10-methyl-9,10-dihydroacridine as a substrate. PMID:24219426

  10. Abrupt Intralesional Color Change on Dermoscopy as a New Indicator of Early Superficial Spreading Melanoma in a Japanese Woman.

    PubMed

    Sadayasu, Anna; Tanaka, Masaru; Maumi, Yoshifumi; Ikeda, Eriko; Sawada, Mizuki; Ishizaki, Sumiko; Murakami, Yoshiyuki; Fujibayashi, Mariko

    2015-01-01

    Diagnosis of superficial spreading melanoma in the early stage is often difficult, even with dermoscopy. We report the case of a 37-year-old Japanese woman with superficial spreading melanoma in her left buttock. The lesion developed 20 years before becoming visible and gradually enlarged over the past few years without any symptoms. Physical examination showed a well-demarcated dark-brown macule 10 mm in diameter. Dermoscopy demonstrated a central dark area with a blue-grey structureless area, a milky-red area with irregular blue-grey dots or globules suggestive of regression structures, and multifocal black pigmentation with whitish scaly areas. An abrupt intralesional change in color from a central dark area to a peripheral light-brown area was also seen. The peripheral area showed an atypical pigment network with an obscure mesh and holes. Histopathologic examination of the lesion showed acanthosis with melanocytic proliferation and nuclear atypia, a band-like lymphocytic infiltrate, melanophages and a few nests of melanocytes just beneath the epidermis. The epidermal melanocytes were positive for S-100, Melan-A and HMB-45, but the dermal nests of melanocytes were negative for HMB-45 and positive for S-100 and Melan-A. A diagnosis of superficial spreading melanoma with a tumor thickness of 0.4 mm (pT1aN0M0, stage 1A) was established based on the clinical, dermoscopic and histopathologic findings. This case suggests that dermoscopy is useful in the diagnosis of this condition. An abrupt intralesional change of color might be a new indicator of early superficial spreading melanoma.

  11. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS).

    PubMed

    Cruz-Jentoft, Alfonso J; Landi, Francesco; Schneider, Stéphane M; Zúñiga, Clemente; Arai, Hidenori; Boirie, Yves; Chen, Liang-Kung; Fielding, Roger A; Martin, Finbarr C; Michel, Jean-Pierre; Sieber, Cornel; Stout, Jeffrey R; Studenski, Stephanie A; Vellas, Bruno; Woo, Jean; Zamboni, Mauro; Cederholm, Tommy

    2014-11-01

    to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected. prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function. prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society.

  12. Synthesis, Characterization and Conductivity Study of Poly(vinyl 4-HYDROXY-3-METHOXY Benzal) and its Sodio Salt in Solid State

    NASA Astrophysics Data System (ADS)

    Borah, P.; Hussain, S.; Dutta, A.

    Among the various ion-conducting materials, polymer salt complexes are of current interest due to their possible application as solid electrolyte as well as their physical nature in advanced high-energy electrochemical devices such as batteries, fuel cells, electrochromic display devices, photo electro-chemical solar cells52-55 etc. The main advantages of polymeric electrolytes are their mechanical properties, ease of fabrication of thin films of desired sizes and their ability to form proper electrode-electrolyte contact. Polymer electrolyte usually consists of a polymer and a salt and is considered to be solid solutions in which the polymer functions as solvent. In the present paper the synthesis, characterization and the conductivity study of the polymer poly (vinyl 4-hydroxy-3-methoxy benzal) (PV-HMB) and its sodio salt (PV-HMB-Na) have been reported. The polymer was prepared by carrying out homogenous acetalization between the prepolymer poly vinylalcohol (PVA) and 4-hydroxy-3-methoxy benzaldehyde (vanilline). PVA was dissolved in dimethyl formamide (DMF) and lithium chloride (LiCl) system i.e., in non-aqueous medium. The sodio salt was prepared by alkalization. The polymer and its salt were characterized by IR, 1H NMR and DSC. Frequency and temperature dependence of ac conductivity has been studied to learn about the electrical conduction behaviour in this material. The electrical conductivity of the new polymeric salt was found to be in the range 10-4 to 10-6 Scm-1. There is about 103 to 104 fold increase in the conductivity of the new polymer salt. Apparent activation energy of the polymer and its salt were found to be 0.139 and 0.08998 ev respectively.

  13. Muscle Oxygen Changes following Sprint Interval Cycling Training in Elite Field Hockey Players

    PubMed Central

    Jones, Ben; Hamilton, David K.; Cooper, Chris E.

    2015-01-01

    This study examined the effects of Sprint Interval Cycling (SIT) on muscle oxygenation kinetics and performance during the 30-15 intermittent fitness test (IFT). Twenty-five women hockey players of Olympic standard were randomly selected into an experimental group (EXP) and a control group (CON). The EXP group performed six additional SIT sessions over six weeks in addition to their normal training program. To explore the potential training-induced change, EXP subjects additionally completed 5 x 30s maximal intensity cycle testing before and after training. During these tests near-infrared spectroscopy (NIRS) measured parameters; oxyhaemoglobin + oxymyoglobin (HbO2+ MbO2), tissue deoxyhaemoglobin + deoxymyoglobin (HHb+HMb), total tissue haemoglobin (tHb) and tissue oxygenation (TSI %) were taken. In the EXP group (5.34±0.14 to 5.50±0.14m.s-1) but not the CON group (pre = 5.37±0.27 to 5.39±0.30m.s-1) significant changes were seen in the 30-15IFT performance. EXP group also displayed significant post-training increases during the sprint cycling: ΔTSI (−7.59±0.91 to −12.16±2.70%); ΔHHb+HMb (35.68±6.67 to 69.44±26.48μM.cm); and ΔHbO2+ MbO2 (−74.29±13.82 to −109.36±22.61μM.cm). No significant differences were seen in ΔtHb (−45.81±15.23 to −42.93±16.24). NIRS is able to detect positive peripheral muscle oxygenation changes when used during a SIT protocol which has been shown to be an effective training modality within elite athletes. PMID:25807517

  14. Pigmented squamous cell carcinoma of the cheek skin probably arising from solar keratosis.

    PubMed

    Terada, Tadashi; Yamagami, Jun; Fugimoto, Atsushi; Tanaka, Kyoko; Sugiura, Makoto

    2003-07-01

    We report a rare case of pigmented squamous cell carcinoma (SCC) of the cheek skin probably arising from solar keratosis. An 80-year-old man was referred to our clinic because of a black skin nodule in the right cheek. The nodular lesion was 1 cm in diameter, dome-shaped, hard, sharply demarcated, partially erosive and telangiectatic at the border. The lesion was completely excised under the clinical diagnosis of probable seborrheic keratosis. Microscopically, cutaneous horn and mildly atypical squamous epithelia suggestive of previous solar keratosis were present in the surface of the lesion. The lesion consisted of atypical squamous cells with keratinization and intercellular bridges, and it was regarded as SCC. The SCC cells were seen to invade lightly into the upper dermis, where lymphocytic infiltrations and melanophages were noted. Characteristically, heavy deposition of melanin pigment was recognized in the SCC cells as well as in proliferated dendritic and pigment blockade melanocytes that were scattered or colonized within the SCC cell nests. Masson-Fontana stain revealed numerous melanin granules in the SCC cells, as well as in dendritic and pigment blockade melanocytes. Immunohistochemically, the SCC cells were positive for cytokeratins and epithelial membrane antigen, and negative for S-100 protein and HMB45 antigen. Dendritic and pigment blockade melanocytes were negative for cytokeratins, epithelial membrane antigen, and HMB45 antigen, but positive for S-100 protein. The present case suggests that SCC cells of the skin may induce proliferation of melanocytes. The differential diagnosis and the histogenesis of pigmented SCC of the skin are discussed.

  15. The Effect of Levonorgestrel on Fibrinolytic Factors in Human Endometrial Endothelial Cells.

    PubMed

    Pakrashi, Tarita; Taylor, Joelle E; Nelson, Ashley; Archer, David F; Jacot, Terry

    2016-11-01

    The levonorgestrel-releasing intrauterine system is considered a highly effective treatment of heavy menstrual bleeding (HMB). While LNG has established effects on the stromal and glandular compartments of the endometrial tissue, its effect on the endometrial endothelial cells has not been investigated. We examined whether LNG regulates fibrinolytic factors, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) secreted by human endometrial endothelial cells (HEECs) and determined the steroid receptor through which LNG exerts its effect on the endothelium. The HEECs were treated with LNG or progesterone and levels of tPA and plasminogen activator inhibitor 1 (PAI-1) measured. The HEECs were specifically examined for the presence of androgen receptors through Western blot. Levonorgestrel ± flutamide were added to HEECs and the levels of tPA and uPA were examined. An enzyme-linked immunosorbent assay performed on culture media confirmed a statistically significant decrease in tPA levels in cells treated with LNG (77.80% ± 8.0% of control; n = 5, P < .05 vs control) but not progesterone. The androgen receptor (110 kDa) was detected in HEEC lysates. The decrease in tPA was blocked by the addition of flutamide (101.3% ± 16% of control), a classic nonsteroidal androgen receptor blocker. There was no change in uPA or PAI-1 levels in cells treated with LNG. Levonorgestrel decreases tPA levels through the androgen receptor in HEECs. Thus, LNG inhibits tPA secretion by the endometrial endothelial cell. This response suggests reduction in HMB with LNG-IUS could reflect an LNG-mediated promotion of hemostasis. © The Author(s) 2016.

  16. A multimodal assessment of melanin and melanocyte activity in abnormally pigmented hypertrophic scar.

    PubMed

    Travis, Taryn E; Ghassemi, Pejhman; Ramella-Roman, Jessica C; Prindeze, Nicholas J; Paul, Dereck W; Moffatt, Lauren T; Jordan, Marion H; Shupp, Jeffrey W

    2015-01-01

    Using a validated swine model of human scar formation, hyperpigmented and hypopigmented scar samples were examined for their histological and optical properties to help elucidate the mechanisms and characteristics of dyspigmentation. Full-thickness wounds were created on the flanks of red Duroc pigs and allowed to heal. Biopsies from areas of hyperpigmentation, hypopigmentation, and uninjured tissue were fixed and embedded for histological examination using Azure B and primary antibodies to S100B, HMB45, and α-melanocyte-stimulating hormone (α-MSH). Spatial frequency domain imaging (SFDI) was then used to examine the optical properties of scars. Hyperpigmentation was first noticeable in healing wounds around weeks 2 to 3, gradually becoming darker. There was no significant difference in S100B staining for the presence of melanocytes between hyperpigmented and hypopigmented scar samples. Azure B staining of melanin was significantly greater in histological sections from hyperpigmented areas than in sections from both uninjured skin and hypopigmented scar (P < .0001). There was significantly greater staining for α-MSH in hyperpigmented samples compared with hypopigmented samples (P = .0121), and HMB45 staining was positive for melanocytes in hyperpigmented scar. SFDI at a wavelength of 632 nm resulted in an absorption coefficient map correlating with visibly hyperpigmented areas of scars. In a red Duroc model of hypertrophic scar formation, melanocyte number is similar in hyperpigmented and hypopigmented tissues. Hyperpigmented tissues, however, show a greater amount of melanin and α-MSH, along with immunohistochemical evidence of stimulated melanocytes. These observations encourage further investigation of melanocyte stimulation and the inflammatory environment within a wound that may influence melanocyte activity. Additionally, SFDI can be used to identify areas of melanin content in mature, pigmented scars, which may lead to its usefulness in wounds at earlier

  17. Reelin and its receptors, VLDLR and ApoER2, in melanocytic nevi

    PubMed Central

    Mihail, A; Coman, G; Staniceanu, F; Coman, L; Zurac, S; Coman, OA

    2017-01-01

    Reelin is an extracellular signaling protein synthesized by Cajal-Retius cells in utero and early after birth, its presence being signaled in adult life too. Reelin acts on its receptors, VLDLR and ApoER2, acting on cytoskeleton, controlling migration and subsequently positioning and stabilizing the cortical neurons. We investigated the reelin presence and its receptors, VLDLR and ApoER2, in melanocytic nevi considering the neural crest origin of the nevus cells and their migration into skin during embrionary period. Melanocytic nevi present a strict cellular architecture and an increased malignant transforming capacity. We investigated reelin presence in 32 melanocytic nevi (5 junctional, 27 compound or 14 dysplastic nevi and 18 non dysplastic nevi). The assessment of reelin presence was performed by histological semiquantitative criteria. Results showed the presence of reelin in 29 cases (29/ 32). The presence of reelin was elevated in junctional areas as in dysplastic nevi. VLDLR presented positive values in 16 cases (16/ 32) and ApoER2 was weak positive in 7 cases. Reelin or its receptors was peritumorally absent. Our study showed the presence of reelin in nevus cells from cutaneous melanocytic nevi and, in these cells, only the VLDLR receptor was present in half of the cases. The significance of the reelin presence in cutaneous nevus cells may be hypothetically considered correlated with the position maintenance of the nevus cells or migration of these cells in malignant transforming situation. Abbreviations: ApoER2 = apolipoprotein receptor 2, VLDLR = very low density lipoprotein receptor, DAB-1 = DIABLO protein, HMB45 = gene HMB45 PMID:28255385

  18. Immunohistochemical diagnosis of canine oral amelanotic melanocytic neoplasms.

    PubMed

    Smedley, R C; Lamoureux, J; Sledge, D G; Kiupel, M

    2011-01-01

    Definitive diagnosis of canine oral melanocytic neoplasms is often difficult because of variability in pigmentation and cellular pleomorphism. These neoplasms can resemble carcinomas, sarcomas, and round cell neoplasms, which differ in prognosis and treatment. A variety of immunohistochemical antibodies have been used for diagnosis of melanocytic neoplasms in humans and dogs; however, sensitivity and specificity of many markers have not been determined in amelanotic melanocytic neoplasms in dogs. The authors investigated a comprehensive panel of immunohistochemical markers in 49 canine oral amelanotic melanocytic neoplasms--namely, Melan-A, PNL2, HMB-45, microphthalmia transcription factor (MiTF), S-100, tyrosine hydroxylase, tyrosinase, tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2), and CD34. Ten well-differentiated cutaneous soft tissue spindle cell sarcomas were negative controls. Melan-A, PNL2, TRP-1, and TRP-2 were highly sensitive and 100% specific for the diagnosis of canine oral amelanotic melanocytic neoplasms. S-100 and MiTF showed high sensitivity but were less specific; that is, they also labeled a proportion of the soft tissue spindle cell sarcomas. HMB-45, tyrosinase, and tyrosine hydroxylase were 100% specific but had low sensitivities. CD34 did not label any of the melanocytic neoplasms but did label 80% of the soft tissue spindle cell sarcomas. A cost-effective and efficient immunodiagnostic cocktail containing antibodies against PNL2, Melan-A, TRP-1, and TRP-2 was created that had 100% specificity and 93.9% sensitivity in identifying canine oral amelanotic melanocytic neoplasms. The spindloid variant was the variant with the lowest sensitivity to the cocktail. The likelihood of correctly diagnosing canine oral amelanotic melanocytic neoplasms was dramatically higher when biopsy samples contained ample overlying and adjacent epithelium.

  19. Endometrial resection and ablation techniques for heavy menstrual bleeding.

    PubMed

    Lethaby, Anne; Penninx, Josien; Hickey, Martha; Garry, Ray; Marjoribanks, Jane

    2013-08-30

    Heavy menstrual bleeding (HMB) is a significant health problem in premenopausal women; it can reduce their quality of life and cause anaemia. First-line therapy has traditionally been medical therapy but this is frequently ineffective. On the other hand, hysterectomy is obviously 100% effective in stopping bleeding but is more costly and can cause severe complications. Endometrial ablation is less invasive and preserves the uterus, although long-term studies have found that the costs of ablative surgery approach the cost of hysterectomy due to the requirement for repeat procedures. A large number of techniques have been developed to 'ablate' (remove) the lining of the endometrium. The gold standard techniques (laser, transcervical resection of the endometrium and rollerball) require visualisation of the uterus with a hysteroscope and, although safe, require skilled surgeons. A number of newer techniques have recently been developed, most of which are less time consuming. However, hysteroscopy may still be required as part of the ablative techniques and some of these techniques must be considered to be still under development, requiring refinement and investigation. To compare the efficacy, safety and acceptability of of endometrial destruction techniques to reduce heavy menstrual bleeding (HMB) in premenopausal women. We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials CENTRAL), MEDLINE, EMBASE, CINAHL, and PsycInfo, (from inception to June 2013). We also searched trials registers, other sources of unpublished or grey literature and reference lists of retrieved studies, and made contact with experts in the field and pharmaceutical companies that manufacture ablation devices. Randomised controlled trials (RCTs) comparing different endometrial ablation techniques in women with a complaint of HMB without uterine pathology were eligible. The outcomes included

  20. The correlation of TRPM1 (Melastatin) mRNA expression with microphthalmia-associated transcription factor (MITF) and other melanogenesis-related proteins in normal and pathological skin, hair follicles and melanocytic nevi

    PubMed Central

    Lu, Song; Slominski, Andrzej; Yang, Sung-Eun; Sheehan, Christine; Ross, Jeffrey; Carlson, J. Andrew

    2010-01-01

    Background Melastatin (TRPM1), a.k.a. transient receptor potential cation channel, subfamily M, member 1 (TRPM-1) regulates melanocyte differentiation and proliferation. TRPM1 is transcriptionally regulated by the essential melanocyte transcription factor MITF (microphthalmia-associated transcription factor). For the most part, MITF expression is preserved during melanoma progression, while TRPM1 mRNA expression decreases or is completely lost. The loss of TRPM1 is associated with melanomas that are more aggressive. Objective To assess the relationship between TRPM1 mRNA expression and the expression of MITF and nine other markers of melanocytes and melanin-related proteins by immunohistochemistry in normal skin, scars, hair follicles and ordinary melanocytic nevi. Methods Samples of normal skin (n = 102; from tumor excisions and plastic procedures), scars (n = 5; from re-excision specimens) and compound melanocytic nevi (n = 4) were evaluated for the presence of TRPM1 mRNA transcripts as detected by chromogenic in situ hybridization (CISH). Immunohistochemical techniques were used to detect melanin-related proteins including: MITF, S100 protein, Mart-1, tyrosinase, Mel5, HMB45, tyrosinase-related protein-1 (TRP1), TRP2 and α-melanocyte stimulating hormone (αMSH). The labeling index (LI) was defined as the number of intraepidermal cells expressing mRNA or protein per one hundred basal keratinocytes. Results A wide range of LI was found for all markers (0–33 positive cells/100 keratinocytes). When these LI were compared, no significant differences in the expression of MITF, S100, Mart1, tyrosinase proteins and TRPM1 mRNA were identified. The LI for TRPM1 mRNA expression ranged from 74% of that for MITF to 86% for tyrosinase. The LI for TRP-1, TRP-2 and Mel5 was similar to that of TRPM1, while HMB-45 had a significantly lower LI than all other markers. TRPM1 mRNA correlated most tightly with MITF and tyrosinase expression (r = 0.81 and 0.68, respectively, both p

  1. Premenopausal abnormal uterine bleeding and risk of endometrial cancer.

    PubMed

    Pennant, M E; Mehta, R; Moody, P; Hackett, G; Prentice, A; Sharp, S J; Lakshman, R

    2017-02-01

    Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding. Search of PubMed, Embase and the Cochrane Library from database inception to August 2015. Studies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding. Data were independently extracted by two reviewers and cross-checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study. Sixty-five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23-0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96-1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04-0.32%, n = 8352; 9 cases) compared with inter-menstrual bleeding (IMB) (0.52%, 95% CI 0.23-1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases. The risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co-morbidities is needed. Contrary to practice, premenopausal women with heavy periods or inter-menstrual bleeding rarely require biopsy. © 2016 The Authors BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal

  2. Exposure to the mass media, body shape concerns, and use of supplements to improve weight and shape among male and female adolescents.

    PubMed

    Field, Alison E; Austin, S Bryn; Camargo, Carlos A; Taylor, C Barr; Striegel-Moore, Ruth H; Loud, Keith J; Colditz, Graham A

    2005-08-01

    To assess the prevalence and correlates of products used to improve weight and shape among male and female adolescents. A cross-sectional study was conducted of 6212 girls and 4237 boys who were 12 to 18 years of age and enrolled in the ongoing Growing Up Today Study. The outcome measure was at least weekly use of any of the following products to improve appearance, muscle mass, or strength: protein powder or shakes, creatine, amino acids/hydroxy methylbutyrate (HMB), dehydroepiandrosterone, growth hormone, or anabolic/injectable steroids. Approximately 4.7% of the boys and 1.6% of the girls used protein powder or shakes, creatine, amino acids/HMB, dehydroepiandrosterone, growth hormone, or anabolic/injectable steroids at least weekly to improve appearance or strength. In multivariate models, boys and girls who thought a lot about wanting more defined muscles (boys: odds ratio [OR]: 1.6; 95% confidence interval [CI]: 1.1-2.2; girls: OR: 2.3; 95% CI: 1.2-3.2) or were trying to gain weight (boys: OR: 3.0; 95% CI: 2.0-4.6; girls: OR: 4.3; 95% CI: 1.6-11.4) were more likely than their peers to use these products. In addition, boys who read men's, fashion, or health/fitness magazines (OR: 2.3; 95% CI: 1.1-4.9) and girls who were trying to look like women in the media (OR: 2.9; 95% CI: 1.4-4.0) were significantly more likely than their peers to use products to improve appearance or strength, but hours per week watching television, watching sports on television, and participation in team sports were not independently associated with using products to improve appearance or muscle mass. Girls and boys who frequently thought about wanting toned or well-defined muscles were at increased risk for using potentially unhealthful products to enhance their physique. These results suggest that just as girls may resort to unhealthful means to achieve a low body weight, girls and boys may also resort to unhealthful means to achieve other desired physiques.

  3. Photocatalytic Oxygenation of Substrates by Dioxygen with Protonated Manganese(III) Corrolazine.

    PubMed

    Jung, Jieun; Neu, Heather M; Leeladee, Pannee; Siegler, Maxime A; Ohkubo, Kei; Goldberg, David P; Fukuzumi, Shunichi

    2016-04-04

    UV-vis spectral titrations of a manganese(III) corrolazine complex [Mn(III)(TBP8Cz)] with HOTf in benzonitrile (PhCN) indicate mono- and diprotonation of Mn(III)(TBP8Cz) to give Mn(III)(OTf)(TBP8Cz(H)) and [Mn(III)(OTf)(H2O)(TBP8Cz(H)2)][OTf] with protonation constants of 9.0 × 10(6) and 4.7 × 10(3) M(-1), respectively. The protonated sites of Mn(III)(OTf)(TBP8Cz(H)) and [Mn(III)(OTf)(H2O)(TBP8Cz(H)2)][OTf] were identified by X-ray crystal structures of the mono- and diprotonated complexes. In the presence of HOTf, the monoprotonated manganese(III) corrolazine complex [Mn(III)(OTf)(TBP8Cz(H))] acts as an efficient photocatalytic catalyst for the oxidation of hexamethylbenzene and thioanisole by O2 to the corresponding alcohol and sulfoxide with 563 and 902 TON, respectively. Femtosecond laser flash photolysis measurements of Mn(III)(OTf)(TBP8Cz(H)) and [Mn(III)(OTf)(H2O)(TBP8Cz(H)2)][OTf] in the presence of O2 revealed the formation of a tripquintet excited state, which was rapidly converted to a tripseptet excited state. The tripseptet excited state of Mn(III)(OTf)(TBP8Cz(H)) reacted with O2 with a diffusion-limited rate constant to produce the putative Mn(IV)(O2(•-))(OTf)(TBP8Cz(H)), whereas the tripseptet excited state of [Mn(III)(OTf)(H2O)(TBP8Cz(H)2)][OTf] exhibited no reactivity toward O2. In the presence of HOTf, Mn(V)(O)(TBP8Cz) can oxidize not only HMB but also mesitylene to the corresponding alcohols, accompanied by regeneration of Mn(III)(OTf)(TBP8Cz(H)). This thermal reaction was examined for a kinetic isotope effect, and essentially no KIE (1.1) was observed for the oxidation of mesitylene-d12, suggesting a proton-coupled electron transfer (PCET) mechanism is operative in this case. Thus, the monoprotonated manganese(III) corrolazine complex, Mn(III)(OTf)(TBP8Cz(H)), acts as an efficient photocatalyst for the oxidation of HMB by O2 to the alcohol.

  4. [Nutritional status in university students: its relation to the number of daily intakes and macronutrients consumption].

    PubMed

    Pi, Romina Antonella; Vidal, Paula Daniela; Brassesco, Bárbara Romina; Viola, Lorena; Aballay, Laura Rosana

    2015-04-01

    Introducción: existe una creciente evidencia científica de que la nutrición ejerce una influencia tanto positiva como negativa en la salud a lo largo de la vida. Diversos autores han destacado que la población universitaria es un grupo especialmente vulnerable desde el punto de vista nutricional ya que se caracteriza por omitir comidas con frecuencia y realizar pequeñas ingestas repetidas veces entre las comidas principales. Objetivo General: establecer la relación existente entre el número de ingestas alimentarias diarias (NIAD), el consumo de macronutrientes y el estado nutricional (EN) en estudiantes de 23-33 años de la Universidad Tecnológica Nacional (UTN), de la ciudad de Córdoba, en el año 2013. Métodos: se utilizó un diseño prospectivo de tipo descriptivo simple correlacional de corte transversal. Se realizó análisis descriptivo e inferencial mediante modelos de regresión logística múltiple. Resultados: de la muestra analizada casi un 50% presentó sobrepeso (SP) y un 40% grasa corporal (GC) elevada. En relación al número de ingestas, los estudiantes que realizaron menos de 4 y más de 6 ingestas tuvieron 2 veces más chance de presentar exceso de peso y de GC. A medida que aumenta la edad también lo hacen los depósitos de GC, y cuando disminuyen los niveles de actividad física (AF) aumenta la chance de presentar un índice de masa corporal (IMC) y GC elevada. Por otro lado, el consumo excesivo de glúcidos aumenta la chance de presentar GC elevada y SP, y el de proteínas y lípidos, el riesgo de GC elevada. Conclusión: Se reconoce al NIAD inferior o superior al recomendado, el bajo nivel de AF, el elevado consumo de carbohidratos, y la edad superior a 29 años como variables relacionados con el SP y la GC elevada.

  5. Establishment of a new continuous clear cell sarcoma cell line. Morphological and cytogenetic characterization and detection of chimaeric EWS/ATF-1 transcripts.

    PubMed

    Hiraga, H; Nojima, T; Abe, S; Yamashiro, K; Yamawaki, S; Kaneda, K; Nagashima, K

    1997-07-01

    Clear cell sarcoma (CCS), a rare tumour of deep soft tissues, often has a t(12; 22) (q13; q12) translocation that induces the formation of a hybrid EWS/ATF-1 gene. To investigate these alterations further, we established a new continuous cell line directly from a CCS taken from a 9-year-old girl. The cultures were characterized with respect to morphological, ultrastructural, immunohistochemical and karyotypical features and were tested by reverse transcription PCR (RT-PCR) for chimaeric EWS/ATF-1 transcripts. The continuous cell line, designated KAO, is tumorigenic in nude mice, and the resultant tumours resemble the primary CCS. The tumour cells and the cultured cells have melanosomes in their cytoplasm and are immunoreactive with the melanoma-specific antibody HMB45, but do not express S-100 protein. The cultured CCS cells have the t(12; 22)(q13; q12) translocation and express the hybrid EWS/ATF-1 gene. No transcripts of the hybrid gene were detected in a malignant cutaneous melanoma tested simultaneously. Although CCS and malignant melanoma are morphologically related, the present results suggest that their geneses differ at the chromosome and molecular levels. They also indicate that chromosome analysis and detection of fusion EWS/ATF-1 transcripts may be useful adjuvant tools for the diagnosis of CCS.

  6. A rare case of TFE-related pigmented renal tumor with overlapping features between melanotic Xp11 translocation renal cancer and Xp11 renal cell carcinoma with melanotic features.

    PubMed

    Cardili, Leonardo; Wrublevsky Pereira, Gregório; Viana, Cristiano Ribeiro

    2017-02-16

    In recent years, an increasing number of TFE3 rearrangement-associated tumors with melanotic features have been reported as primary neoplasm in different anatomical sites, including the kidney. Melanotic Xp11 translocation renal cancer (MXTRC) and Xp11 renal cell carcinoma with melanotic features (XRCCM) have been proposed to be main categories for pigmented lesions in the microophthalmia-associated transcription factor (MiTF/TFE3) family of renal tumors that may show variable degrees of melanocytic differentiation. Herein we report a rare case of TFE3-related pigmented renal tumor showing unusual immunoexpression of cytokeratins (AE1/AE3) and renal cell carcinoma markers (RCC, CD10). Cathepsin-K and Vimentin were diffusely positive whereas melanocytic markers (HMB-45 and Melan-A) displayed weak and patchy expression. We found no labelling for PAX-8, muscle markers (desmin, smooth muscle actin, muscle-specific actin and caldesmon) and S-100. TFE3 fusion was confirmed by break-apart fluorescence in situ hybridization (FISH). This case corroborates previous evidence for overlap in the TFE3-associated cancer family and illustrates that it may not be possible to set a clear cutoff between epithelial (XRCCM) and mesenchymal (MXTRC) subgroups.

  7. Lack of standards for the detection of melanoma in sentinel lymph nodes: a survey and recommendations.

    PubMed

    Dekker, John; Duncan, Lyn M

    2013-11-01

    Detection of microscopic melanoma metastases in sentinel lymph nodes drives clinical care; patients without metastases are observed, and patients with metastases are offered completion lymphadenectomy and adjuvant therapy. We sought to determine common elements in currently used analytic platforms for sentinel lymph nodes in melanoma patients. An electronic survey was distributed to 83 cancer centers in North America. Seventeen responses (20%) were received. The number of sentinel lymph node mapping procedures for melanoma ranged from less than 11 to more than 100 patients per year, with 72% of institutions mapping more than 50 melanoma patients a year. Uniform practices included (1) processing all of the lymph node tissue rather than submitting representative sections and (2) use of immunohistochemical stains if no tumor was identified on the hematoxylin-eosin-stained sections. Significant variability existed regarding the method of sectioning lymph nodes at grossing and in the histology laboratory; most bisected nodes longitudinally (94%) and performed deeper levels into the block (67%), but these were not uniform practices. S-100 was the most commonly used immunohistochemical stain (78%), followed by Melan-A (56%), MART-1 (50%), HMB-45 (44%), tyrosinase (33%), MiTF (11%), and pan-melanoma (6%). There is a need for a standardized platform for detecting melanoma in sentinel lymph nodes. Current practices by a majority of laboratories and findings in the reported literature support the following: histologic evaluation of all lymph node tissue, use of immunohistochemical stains, bisecting lymph nodes longitudinally, and performing deeper levels into the tissue block.

  8. Primary Gliosarcoma of the Optic Nerve: A Unique Adult Optic Pathway Glioma.

    PubMed

    Cimino, Patrick J; Sychev, Yevgeniy V; Gonzalez-Cuyar, Luis F; Mudumbai, Raghu C; Keene, C Dirk

    2016-10-11

    A 90-year-old woman presented with 1-year history of right-sided progressive proptosis, neovascular glaucoma, blindness, and worsening ocular pain. No funduscopic examination was possible because of a corneal opacity. Head CT scan without contrast demonstrated a heterogeneous 4.1 cm (anterior-posterior) by 1.7 cm (transverse) cylindrical mass arising in the right optic nerve and extending from the retrobulbar globe to the optic canal. She underwent palliative enucleation with subtotal resection of the orbital optic nerve and tumor. Pathological examination showed effacement of the optic nerve by an infiltrative high-grade glial neoplasm with biphasic sarcomeric differentiation. Invasion into the uvea and retina was present. The neoplasm was negative for melan-A, HMB45, tyrosinase, synaptophysin, smooth muscle actin, and epithelial membrane antigen. The glioma had strongly intense, but patchy immunopositivity for glial fibrillary acidic protein. Multiple foci of neoplastic cells had pericellular reticulin staining. The overall features were diagnostic of a gliosarcoma (World Health Organization grade IV) of the optic nerve. Postoperative MRI demonstrated postsurgical changes and residual gliosarcoma with extension into the optic chiasm. The patient died 2 and a half months after her enucleation surgery at her nursing home. Autopsy was unavailable due to the caregiver wishes, making a definitive cause of death unknown. Gliosarcoma is a rare variant of glioblastoma, and this is the first documented case presenting as a primary neoplasm of the optic nerve.

  9. Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes

    PubMed Central

    Liang, Chunzi; Curry, Benjamin J.; Brown, Patricia L.; Zemel, Michael B.

    2014-01-01

    Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover, β-hydroxy-β-methyl butyrate (HMB), a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5 mM), alanine (0.5 mM), valine (0.5 mM), EX527 (SIRT1 inhibitor, 25 μM), and Compound C (AMPK inhibitor, 25 μM) alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD+, SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event. PMID:25400942

  10. Ulcerative Granular Cell Tumor: A Clinicopathological and Immunohistochemical Study

    PubMed Central

    El-Khalawany, Mohamed; Mosbeh, Al-Sadat; Abd-Al Salam, Fatma; Abou-Bakr, Amany

    2011-01-01

    Granular cell tumor (GCT) is uncommonly presented with cutaneous ulcer. We examined the clinicopathological and immunohistochemical features of this ulcerative form in fourteen cases that may raise the awareness of this variant. The study included 11 males and 3 females with a mean age 31.5 ± 7.42 years. All cases were presented with large solitary ulcer with indurated base, elevated border, skin colored margin, and necrotic floor. Twelve lesions were located on the extremities and two lesions on the genital region. Histologically, the lesions showed dermal infiltrate composed of large polygonal cells with granular cytoplasm and characteristic infiltration of the dermal muscles in all cases. Immunostaining showed positive reaction for S100 (14/14), NSE (14/14), CD68 (5/14), and Vimentin (7/14) while HMB45, CK, EMA, and Desmin were negative. We hope that this paper increases the awareness of ulcerative GCT and consider it in the differential diagnosis of ulcerative lesions. PMID:22132340

  11. Angiomyolipomes épithélioïdes rénal bénin: à propos de deux cas

    PubMed Central

    Bagayogo, Tidiani; Othmane, Yddoussalah; Tarik, Karmouni; Khalid, Elkhader; Abdellatif, Koutani; Ahmed, Ibn Attya Andaloussi

    2015-01-01

    Les angiomyolipomes épithélioïdes rénaux (AMLeR) sont des tumeurs rares (identifiées chez moins de 0,1 patients pour 1000 habitants) et représentent 8% des angiomyolipomes (AML) opérés. Il a longtemps été considérécomme un hamartome mais plusieurs articles récents font penser qu'il s'agir d'une tumeur dérivant de cellules épithélioïdespérivasculaires. L'angiomyolipome épithélioïde est une forme rare d'angiomyolipome à potentiel malin, composé decellules épithélioïdes posant des problèmes de diagnostic différentiel avec les carcinomes à cellules rénales. L'immunohistochimie,en révélant la positivité des cellules épithélioïdes au marqueur HMB45 est essentielle au diagnostic. Les auteursrapportent l'aspect tomodensitométrique et histologique d'angiomyolipomes épithélioïdes chez deux patientes. PMID:26953738

  12. The role of bronchoscopy in the diagnosis of early lung cancer: a review

    PubMed Central

    Potenza, Rossella; Capozzi, Rosanna; Liparulo, Valeria; Puma, Francesco; Yasufuku, Kazuhiro

    2016-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide with an overall 5-year survival rate of 17% after diagnoses. Indeed many patients tend to have a very poor prognosis, due to being diagnosed at an advanced stage. Conversely patients who are diagnosed at an early stage have a 5-year survival >70%, indicating that early detection of lung cancer is crucial to improve survival. Although flexible bronchoscopy is a relatively non-invasive procedure for patients suspected of having lung cancer, only 29% of carcinoma in situ (CIS) and 69% of microinvasive tumors were detectable using white light bronchoscopy (WLB) alone. As a result, in the past two decades, new bronchoscopic techniques have been developed to increase the yield and diagnostic accuracy, such as autofluorescence bronchoscopy (AFB), narrow band imaging (NBI) and high magnification bronchovideoscopy (HMB). However, due to the low specificity and the limitation to detect only proximal bronchial tree, new probe-based technologies have been introduced: radial endobronchial ultrasound (R-EBUS), optical coherence tomography (OCT), confocal laser endomicroscopy (CLE) and laser Raman spectroscopy (LRS). To date, although tissue biopsy remains the gold standard for diagnosing malignant/premalignant airway disease and some techniques are still investigational, bronchoscopic technologies can be considered the safest and most accurate tools to evaluate both central and distal airway mucosa. PMID:28066614

  13. Comparative evaluation of diode laser ablation and surgical stripping technique for gingival depigmentation: A clinical and immunohistochemical study

    PubMed Central

    Bakutra, Gaurav; Shankarapillai, Rajesh; Mathur, Lalit; Manohar, Balaji

    2017-01-01

    Introduction: There are various treatment modalities to remove the black patches of melanin pigmentation. The aim of the study is to clinically compare the diode laser ablation and surgical stripping technique for gingival depigmentation and to evaluate their effect on the histological changes in melanocyte activity. Materials and Methods: A total of 40 sites of 20 patients with bilateral melanin hyperpigmentation were treated with the surgical stripping and diode laser ablation technique. Change in Hedin index score, change in area of pigmentation using image analyzing software, pain perception, patient preference of treatment were recorded. All 40 sites were selected for immunohistochemical analysis using HMB-45 immunohistochemical marker. Results: At 12 months post-operative visit, in all sites, repigmentation was observed with different grades of Hedin index. Paired t-test, analysis of variance, and Chi-square tests were used for statistical analysis. Repigmentation in surgical stripping is significantly lesser compared to laser ablation. Lesser numbers of melanocytes were found on immunohistological examination at 12 months postoperatively. Comparison for patient preference and pain indices give statistically significant values for diode laser techniques. Conclusion: Gingival hyperpigmentation is effectively managed by diode laser ablation technique and surgical stripping method. In this study, surgical stripping technique found to be better compared to diode laser ablation. PMID:28539864

  14. [Eating habits of a group of professional volleyball players].

    PubMed

    Gacek, Maria

    2011-01-01

    The aim of the research was an analysis of the eating habits of professional volleyball players according to their sex and age. The research has been carried out on a group of 210 men players and women players at the age of 13-25, representatives of sports clubs in Ostrołeka, Myślenice, Bydgoszcz and Warszawa. The research has revealed a limited realisation of rational diets by both men and women players. The most common mistakes made by them include a smaller number of meals during the day than recommended (especially among men), taking up training on empty stomach and insufficient frequency of consumption of dairy products, fish, vegetables and fruit. The research has also revealed excessive consumption of sweets, sweet sparkling drinks and fast food (mainly among men). The examined players to some extent only apply regular strategies of rehydration of their organisms. A high percentage of them do not pay attention to supplementation of liquids after an effort or they drink a lot of liquids at one time. The most frequently chosen drinks were mineral water and isotonic drinks. Supplementation was applied by a small percentage of the players, mainly men, who most often chose vitamins, Izostar, creatine, L-carnitine and HMB.

  15. Multiple clear-cell sarcomas of small intestine with parotid gland metastasis: A case report

    PubMed Central

    Su, Hao; Liu, Wen-Sheng; Ren, Wen-Hao; Wang, Peng; Shi, Lei; Zhou, Hai-Tao

    2017-01-01

    Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays melanocytic differentiation with a distinct molecular profile. It is rarely localized in the gastrointestinal tract. Herein we reported a case of multiple synchronous clear-cell sarcomas of the gastrointestinal tract with parotid gland metastasis. A 51-year-old male patient presented with a growing painless mass under the right ear. A preoperative positron emission tomography/computed tomography showed multiple intestinal masses and a mass in the right parotid with increased glucose uptake, and he underwent operative treatment with resection of three tumors in the jejunum and ileum and then received a right parotidectomy. Postoperative pathological examination showed that cells in the intestinal tumor were consistent with clear-cell sarcoma of the gastrointestinal tract, and the malignant cells in the parotid gland were similar to the intestinal tumor. Immunohistochemical studies revealed positive expression of HMB-45, Melan-A, and S-100. EWSR1 gene fusion transcripts were undetectable by fluorescence in situ hybridization. PMID:28405155

  16. Paraganglioma-like dermal melanocytic tumor: a unique entity distinct from cellular blue nevus, clear cell sarcoma, and cutaneous melanoma.

    PubMed

    Deyrup, Andrea T; Althof, Pamela; Zhou, Ming; Morgan, Michael; Solomon, Alvin R; Bridge, Julia A; Weiss, Sharon W

    2004-12-01

    We are reporting a previously undescribed primary dermal melanocytic tumor identified by reviewing all dermal melanocytic tumors referred in consultation that did not qualify histologically as a previously described entity. From these cases, 8 were remarkably similar. We termed them "paraganglioma-like dermal melanocytic tumor" (PDMT) based on their nested growth pattern. This term is used descriptively and does not imply any histogenetic or biologic similarity to true paraganglioma. PDMT is primarily a tumor of the extremities of adult females (18-53 years, mean 35 years; males 2; females 6) which present as a dermal nodule (range, 0.5-4.2 cm; mean, 1.4 cm) composed of nests of clear to amphophilic oval cells separated by delicate fibrous strands. Nuclear atypia was mild and mitotic activity low (1-4 mitoses/10 HPF). Melanin was not obvious on light microscopy. Tumors expressed S-100 protein (8 of 8), Melan-A (4 of 8), HMB-45 (8 of 8), and microphthalmia transcription factor (8 of 8) and lacked pancytokeratin (8 of 8) and smooth muscle actin (8 of 8). FISH analysis of 5 cases revealed an intact EWS gene locus, supporting absence of the clear cell sarcoma 12;22 translocation. Follow-up information in 8 patients (range, 35-92 months; mean, 54 months) indicated that all were alive without disease. PDMT comprises a clinically and pathologically unique subtype of dermal melanocytic tumors. Our study suggests a benign course, although a lesion of low malignant potential cannot be excluded.

  17. Spitz nevus arising in the eyelid of a teenager.

    PubMed

    Shields, Patrick W; Jakobiec, Frederick A; Stagner, Anna M; Yoon, Michael K

    2016-01-01

    A 16-year-old boy developed over a 2-month interval a lightly pigmented left upper eyelid lesion measuring 1.5 mm in greatest diameter that, when excised, microscopically was hypercellular and composed almost exclusively of nonpigmented epithelioid cells that created florid, large intraepidermal junctional nests and sheets and nests of subepidermal cells. The diagnosis was a Spitz nevus. HMB-45, MART-1, and microphthalmia-associated transcription factor were all positive and established the melanocytic nature of the benign tumor. The Ki-67 proliferation index (5%) and 2 mitoses/mm(2) were both low; p16 protein was immunohistochemically identified in the nevoid cells. We review the clinical, histopathologic, and other immunohistochemical features of this entity and provide a brief differential diagnosis (including separation from a Spitzoid melanoma). This is only the third eyelid Spitz nevus reported in the literature and is the most fully characterized immunohistochemically. At their present stage of development, contemporary immunohistochemical biomarkers, while providing supplemental information, nonetheless remain less than definitive in terms of reliably distinguishing benign from malignant Spitz lesions.

  18. A case report of pigmented mammary Paget's disease mimicking nevus of the nipple.

    PubMed

    Tang, Xiaoyan; Umemura, Shinobu; Kumaki, Nobue; Izumi, Miki; Saito, Yuki; Suzuki, Yasuhiro; Ozawa, Akira; Tokuda, Yutaka

    2014-05-01

    A 43-year-old Japanese woman consulted our hospital for a pigmented lesion on her right nipple. Two years later, the lesion became enlarged, measuring 5 × 5 mm. It was dark brown, had an irregular shape and relatively clear borders. Incisional biopsy yielded a pathological diagnosis of junctional nevus of the skin. An additional 2 years later, a small mass developed under the right nipple area and core needle biopsy yielded a pathologic diagnosis of invasive ductal carcinoma. Partial resection of the right EC areas included the skin of the nipple and sentinel lymph node biopsy was performed. Histologically, the skin of the nipple demonstrated small clusters of pigmented carcinoma cells that were low molecular weight cytokeratin (CAM5.2) positive. Most of the carcinoma cells were small and did not have abundant cytoplasm, but nuclear enlargement and prominent nucleoli indicated malignancy, and the cytoplasm was pale compared with that of the surrounding squamous epithelial cells. Scattered dendritic melanocytes were identified by S-100 protein and HMB-45 immunohistochemically. In the upper dermis, carcinoma cells also involved the lactiferous ducts. A small focus of carcinoma cells that invaded the fat tissues did not contain melanin pigment. The final diagnosis was pigmented mammary Paget's disease. Pigmented lesions on the nipple should be carefully examined, because pigmented mammary Paget's disease sometimes mimics malignant melanoma or junctional nevus.

  19. Melanotic Translocation Renal Cell Carcinoma With a Novel ARID1B-TFE3 Gene Fusion.

    PubMed

    Antic, Tatjana; Taxy, Jerome B; Alikhan, Mir; Segal, Jeremy

    2017-09-04

    A 36-year-old male was found to have a 7.0 cm left upper pole renal mass on renal ultrasound. Following nephrectomy, the mass was grossly ill-demarcated, friable and red-brown, invading renal parenchyma, hilar fat and the renal vein. Microscopically, the tumor had a nested and papillary architecture. The cells demonstrated abundant clear and eosinophilic cytoplasm and focal intracytoplasmic melanin pigment. Nucleoli were prominent. By immunohistochemistry, the tumor was positive for TFE3; HMB-45 stained approximately 5% of tumor cells corresponding to the histologic melanin pigment, which was confirmed with Fontana-Masson stain with bleach. Immunostains for PAX8, CD10, MiTF, and CAIX were negative; keratins Cam 5.2 and AE1/AE3 were focally positive. Targeted next-generation sequencing revealed an ARID1B-TFE3 gene fusion. Melanotic Xp11 renal cell carcinoma is a rare, pigment containing translocation variant demonstrating overlapping features with melanoma and is usually associated with an SFPQ-TFE3 gene fusion. The patient is alive and without evidence of disease 7 years after his diagnosis. The combination of high grade histopathology, the presence of melanin, absent PAX8, keratin positivity, and relatively indolent clinical behavior with a unique translocation may warrant recognition as a distinct renal cell carcinoma translocation subtype.

  20. Vascular leiomyoma of the lung arising from pulmonary artery.

    PubMed

    Terada, Tadashi

    2013-01-01

    Leiomyoma of the lung is extremely rare. The entity is not described in WHO blue book. Less than 100 cases of leiomyoma of the lung have been reported in the literature. However, vascular leiomyoma has not been reported in the literature, to the author's best knowledge. Herein reported is the first case of vascular leiomyoma of the lung arising from smooth muscles of the pulmonary artery. A 62-year-old woman (non-smoker) was found to have a small tumor in the upper lobe in the right lung in routine check. Imaging modalities including CT demonstrated no metastatic lesions. Although clinical cytology and biopsy revealed no malignant cell, right upper lobectomy was performed under the clinical diagnosis of lung carcinoma. Grossly, a white tumor of 1 x 0.8 cm was recognized in the lung. Microscopically, the tumor was connected to the pulmonary arteries. The tumor was composed of mature smooth muscles. Small pulmonary arteries are embedded in the tumor. No lymphatics were seen. Immunohistochemically, the tumor cells were poisitive for alpha-smooth muscle actin, vimentin and Ki-67 (labeling 2%). However, they were negative for cytokeratin (CK) AE1/3, CK CAM5.2, desmin, S100 protein, p53, CD34, KIT, HMB45, estrogen receptor, progesterone receptor, and myoglobin. A pathological diagnosis of primary vascular leiomyoma arising from the smooth muscle of pulmonary artery was made. The patient is now free from tumor, and is now alive 10 year after the operation.

  1. Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course.

    PubMed

    Shaco-Levy, Ruthy; Bean, Sarah M; Vollmer, Robin T; Papalas, John A; Bentley, Rex C; Selim, Maria Angelica; Robboy, Stanley J

    2010-01-01

    The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course was examined: pseudo-invasion, adnexal involvement, signet-ring cells, cytologic atypia, glands formation, epidermal acantholysis, parakeratosis, hyperkeratosis, and chronic inflammation. The recurrence rate after surgical management was 32%, with epidermal acantholysis being the only statistically significant risk factor. Stromal invasion occurred in 10 patients (18%), and was not a statistically significant adverse prognostic indicator, although the single patient who died of the disease had the deepest stromal invasion. Recurrence was more common after resections with positive surgical margins, but this correlation was not statistically significant. Intraoperative frozen section analysis of the margins did not reduce recurrence rate, nor was it useful in attaining permanent free margins. The Paget cells were consistently reactive with cytokeratin-7 and carcinoembryonic antigen and unreactive with S-100 protein, HMB-45, and Mart-1. In addition, the tumor cells were usually positive for mucin stains. This profile helps distinguish vulvar Paget disease from its mimics, Pagetoid squamous cell carcinoma and malignant melanoma.

  2. MiT Family Translocation-Associated Renal Cell Carcinoma: A Contemporary Update With Emphasis on Morphologic, Immunophenotypic, and Molecular Mimics.

    PubMed

    Magers, Martin J; Udager, Aaron M; Mehra, Rohit

    2015-10-01

    Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon subtype of renal cell carcinoma characterized by recurrent gene rearrangements involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia transcription factor (MiT) family, which regulates differentiation in melanocytes and osteoclasts, and MiT family gene fusions activate unique molecular programs that can be detected immunohistochemically. Although the overall clinical behavior of t-RCC is variable, emerging molecular data suggest the possibility of targeted approaches to advanced disease. Thus, distinguishing t-RCC from its morphologic, immunophenotypic, and molecular mimics may have important clinical implications. The differential diagnosis for t-RCC includes a variety of common renal neoplasms, particularly those demonstrating clear cell and papillary features; in addition, because of immunophenotypic overlap and/or shared molecular abnormalities (ie, TFE3 gene rearrangement), a distinctive set of nonepithelial renal tumors may also warrant consideration. Directed ancillary testing is an essential aspect to the workup of t-RCC cases and may include a panel of immunohistochemical stains, such as PAX8, pancytokeratins, epithelial membrane antigen, carbonic anhydrase IX, HMB-45, and Melan-A. Dual-color, break-apart fluorescent in situ hybridization for TFE3 or TFEB gene rearrangement may be helpful in diagnostically challenging cases or when molecular confirmation is needed.

  3. Unusual multicentric angiomyolipoma of knee joint and soft tissue foot.

    PubMed

    Varshney, Manish Kumar; Jain, Manjula; Sud, Alok; Agarwal, Savita; Nain, Manupriya

    2011-01-01

    To report unusual occurrence of angiomyolipoma at intraarticular location with another lesion in the same side foot. A 12-year-old girl was referred to us after initial inconclusive work-up done elsewhere for swelling of left knee joint. There was a 15 × 12 cm swelling in the knee joint partially encasing patella while also a similar hourglass shaped swelling measuring 9 × 4 cm was noted in the same side foot. After clinical and radiological evaluation an excision biopsy was planned for both sites. The specimen sent for histopathological evaluation revealed angiomyolipoma with identical characteristics in the two locations and was HMB45 immunostain negative. Patient was evaluated for possibility of tuberous sclerosis but there was no contributory evidence. Angiomyolipoma is typically a solitary renal tumor with rare occurrence at musculoskeletal sites. Multicentric variety is still infrequent. Intraarticular occurrence of angiomyolipoma presents a diagnostic challenge not only in terms of unfamiliarity but also unusual presentation with absence of characteristic immunostaining and multicentricity requiring careful exclusion of other lesions that may require a more radical approach for treatment. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  4. A Review of the Literature on Extrarenal Retroperitoneal Angiomyolipoma

    PubMed Central

    Venyo, Anthony Kodzo-Grey

    2016-01-01

    Background. Extrarenal retroperitoneal angiomyolipomas are rare. Aim. To review the literature. Results. Angiomyolipomas, previously classified as hamartomas, are now classified as benign tumours. Thirty cases of primary retroperitoneal angiomyolipomas have been reported. Diagnosis of the disease upon is based radiological and pathological findings of triphasic features of (a) fat and (b) blood vessels and myoid tissue. Immunohistochemistry tends to be positive for HMB45, MART1, HHF35, calponin, NKI-C3, and CD117. The lesion is common in women. Treatment options have included the following: (a) radical surgical excision of the lesion with renal sparing surgery or radical nephrectomy in cases where malignant tumours could not be excluded and (b) selective embolization of the lesion alone or prior to surgical excision. One case of retroperitoneal angiomyolipoma was reported in a patient 15 years after undergoing radical nephrectomy for angiomyolipoma of kidney and two cases of distant metastases of angiomyolipoma have been reported following radical resection of the tumour. Conclusions. With the report of two cases of metastases ensuing surgical resection of the primary lesions there is need for academic pathologists to debate and review angiomyolipomas to decide whether to reclassify angiomyolipomas as slow-growing malignant tumours or whether the reported cases of metastases were de novo tumours or metastatic lesions. PMID:26989509

  5. Malignant perivascular epithelioid cell tumor of the kidney with rare pulmonary and ileum metastases

    PubMed Central

    Shi, Huijuan; Cao, Qinghua; Li, Hui; Zhen, Tiantian; Lai, Yingrong; Han, Anjia

    2014-01-01

    Aims: To report one case of malignant perivascular epithelioid cell tumor (PEComa) of the kidney with rare pulmonary and ileum metastases and analyze its clinicopathological features. Methods: We analyzed the clinicopathological features of one case of malignant PEComa of the kidney with pulmonary and ileum metastases. Immunohistochemistry staining was performed. Results: The patient was a 48-year-old man with a renal mass approximately 14 cm × 11 cm × 8 cm in size. Microscopically, the tumor was mainly composed of polygonal epithelioid cells with dense eosinophilic cytoplasm and round nuclei with small nucleoli. Focal tumor cells showed pleomorphism with multinucleated giant cells and prominent nucleoli. The tumor cells nests were surrounded by thick-walled irregular blood vessels. Focal fat cells were found within the tumor. Hemorrhage and coagulative necrosis were also present. The tumor cells were positive for vimentin, HMB45, and Melan-A, and focally positive for SMA and S-100 protein. After 5 years and 5.6 years of nephrectomy, the tumor metastasized to the right lung and ileum, respectively. Conclusion: We first reported one case of malignant PEComa of the kidney with pulmonary and ileum metastases. Metastatic PEComa of the lung and ileum should differentiate from primary carcinoma, metastatic carcinoma, malignant melanoma, and gastrointestinal stromal tumor. PMID:25337291

  6. Malignant perivascular epithelioid cell tumor of mesentery with lymph node involvement: a case report and review of literature

    PubMed Central

    2013-01-01

    Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1309992178882788 Perivascular epithelioid cell tumor (PEComa) is a rare but distinct mesenchymal neoplasm composed of histologically and immunohistochemically unique perivascular epithelioid cells. Due to its relative rarity, little is known about the histogenesis and prognostic factors of this tumor. We describe a case of unusual mesenteric PEComa in a 38-year-old female patient with regional lymph node involvement. Histologically, the tumor was composed of sheet of epithelioid cells with abundant clear or eosinophillic cytoplasms. Extensive coagulative necrosis and a few mitotic figures (2/50 high power field) could be found in tumor. The epithelioid tumor cells were diffusely positive for HMB-45, Melan-A, and focally positive for calponin. One of enlarged mesenteric lymph nodes was observed to be involved by tumor. A diagnosis of malignant mesenteric PEComa with lymph node involvement was made. The patient received chemotherapy after total resection of tumor and segmental resection of involved jejunum. There was no sign of recurrence of tumor found in period of 6-month regular follow-up after chemotherapy. To our knowledge, this is the first case of malignant PEComa in mesentery accompanied with regional lymph node involvement. The literature on this rare tumor is reviewed and diagnostic criteria of malignant PEComa are discussed. PMID:23587410

  7. Spontaneous Splenic Rupture in Melanoma

    PubMed Central

    Oryan, Ahmad; Davari, Aida; Daneshbod, Khosrow; Daneshbod, Yahya

    2014-01-01

    Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin) confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic) rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen. PMID:24795827

  8. Low-frequency spectra of the hexamethylbenzene/tetracyanoethylene electron donor-acceptor complexes in solution studied by terahertz time-domain spectroscopy.

    PubMed

    Yamamoto, Kohji; Kabir, Md Humayun; Hayashi, Michitoshi; Tominaga, Keisuke

    2005-05-07

    We have measured the frequency dependent extinction coefficients and refractive indices of electron donor-acceptor (EDA) complexes consisting of hexamethylbenzene (HMB; electron donor) and tetracyanoethylene (TCNE; electron acceptor) in the low-frequency region by terahertz time-domain spectroscopy (THz-TDS). A mixture of the 1:1 (DA) and 2:1 (D2A) EDA complexes exist in carbon tetrachloride solution, and we successfully obtained the spectral components of the 1:1 and 2:1 EDA complexes separately by analyzing the concentration dependence of the THz spectra. The 1:1 and 2:1 complexes show quite different THz spectra of the extinction coefficient, reflecting unique features of dynamics, fluctuations and intermolecular interactions of these complexes. Polarization-selective THz-TDS on the crystalline DA complex shows two peaks at 53 and 70 cm(-1) in the spectral component perpendicular to the crystal axis. On the other hand, the crystalline D2A complex exhibits peaks at 42 and 50 cm(-1) in the perpendicular spectral component. We compare the obtained spectra of the crystalline complex and the results of molecular orbital calculations at the HF/6-31G(d) level of theory to discuss the intermolecular vibrational modes of the complexes.

  9. Fibrosarcoma of the jaws: two cases of primary tumors with intraosseous growth.

    PubMed

    Angiero, Francesca; Rizzuti, Tommaso; Crippa, Rolando; Stefani, Michele

    2007-01-01

    Fibrosarcoma (FS) is a malignant mesenchymal neoplasm of the fibroblasts that rarely affects the oral cavity. Two cases of primary FS of the jaws with intraosseous growth (2 men, aged 53 and 71 years) are described. Microscopically, in one case the tumor showed an intense proliferation of spindle-shaped cells, varying little in size and shape and arranged in parallel bands, partly crossing each other, with significant mitotic activity and nuclear pleomorphism; the second case was characterized by low cellularity comprising spindle-shaped cells, deposited in a variably fibrous and myxoid stroma. On immunohistochemistry, cells in both cases were strongly immunoreactive for MIB-1 and vimentin, focally positive for CD68, and negative for S-100 protein, pancytokeratin, HMB45, CD34, desmin, smooth muscle actin (SMA) and epithelial membrane antigen (EMA). Based on clinical, histological and immunohistochemical findings, the final diagnosis was FS in the first case, myxofibrosarcoma in the second. Treatment was radical surgery with mandibular reconstruction. After two years, the first patient displayed multiple metastases and died during the third year after the initial diagnosis; the second patient was still alive and doing well five years after treatment. We discuss the differential diagnosis versus other forms of sarcoma, examining the morphological appearance that is frequently very similar, the immunohistochemical expression of MIB-1, vimentin, S-100, CD-34, CD68, EMA, as well as conventional clinicopathological features that may help to distinguish FS from other sarcomas.

  10. Aggressive angiomyxoma of the liver: a case report and literature review.

    PubMed

    Sato, Koki; Ohira, Masahiro; Shimizu, Seiichi; Kuroda, Shintarou; Ide, Kentaro; Ishiyama, Kohei; Kobayashi, Tsuyoshi; Tahara, Hiroyuki; Shiroma, Noriyuki; Arihiro, Koji; Imamura, Michio; Chayama, Kazuaki; Ohdan, Hideki

    2017-08-23

    Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that occurs almost exclusively in the soft tissue of the pelvis and perineum. AAM has both locally infiltrative and recurrent characteristics. Very few cases of AAM occurring outside of the pelvis and perineum have been reported. Here, we report a case of AAM originating in the liver of a 33-year-old female patient. A 33-year-old woman underwent S8 subsegmentectomy after clinical diagnosis of a mucinous cystic neoplasm of the liver. Histological analysis revealed a tumor composed of spindle-shaped cells with vascular proliferation in a myxoid stroma. Immunohistochemically, the tumor cells stained positively for CD34, estrogen receptor (ER), and progesterone receptor (PgR) and negatively for S-100, EMA, CK19, CD99, HMB45, and α-smooth muscle actin. The tumor was diagnosed as AAM originating from the liver. The patient received no adjuvant chemotherapy. No sign of recurrence or distant metastasis has been noted for 10 months after the surgery. We here report a second case of AAM originating from the liver, which is an uncommon location for this particular tumor.

  11. Evaluation of quality of life and cost-effectiveness of definitive surgery and the levonorgestrel intrauterine system as treatment options for heavy menstrual bleeding.

    PubMed

    Adigüzel, Cevdet; Seyfettinoğlu, Sevtap; Aka Satar, Deniz; Arlier, Sefa; Eskimez, Eda; Kaya, Fatma; Nazik, Hakan

    2017-06-12

    This study aimed to compare the levonorgestrel intrauterine system (LNG-IUS) with abdominal hysterectomy (TAH) and total laparoscopic hysterectomy (TLH) as first-line treatments for heavy menstrual bleeding (HMB). Ninety-eight patients aged 20-55 years who complained of regular heavy menstrual bleeding were enrolled in the study. The TAH group included 29 patients, the LNG-IUS group included 34, and the TLH group included 35. These groups were compared in terms of quality of life and the cost-effectiveness of the selected methods. Quality of life was assessed using the 36-Item Short Form (SF-36), and cost-effectiveness was assessed according to the current cost of each approach. The quality of life parameters, with the exception of mental health, improved significantly in the LNG-IUS, TAH, and TLH groups. The mean costs of the LNG-IUS, TAH, and TLH procedures were $99.15 ± 4.90, $538.82 ± 193.00 and $1617.05 ± 258.44, respectively (P < 0.05). Overall, LNG-IUS was the most cost-effective treatment option. The outcome measures of the SF-36 revealed that after 6 months, these treatments were equal in terms of quality of life, except for mental health. LNG-IUS was the most cost-effective approach.

  12. [Primary hepatic lymphoma: an infrequent cause of focal hepatic lesion].

    PubMed

    Balduzzi, Carolina; Yantorno, Martin; Mosca, Iván; Apraiz, Mirta; Velázquez, María J; Puente, María del Carmen; Moragrega, Valeria; Ligorría, Regina; Ottino, Anabel; Belloni, Rodrigo; Barbero, Rodolfo; Jmelniztky, Alejandro; Chopita, Néstor

    2010-12-01

    Primary hepatic lymphoma (PHL) is confined to the liver with no evidence of extrahepatic lymphomatosis. Histopathologically, the PHL belongs to the group of non-Hodgkin's lymphomas and the most common subtype is the diffise large B-cell lymphoma. We present a 72-year-old woman, with no relevant antecedents and the following symptoms: early satiety, abdominal discomfort and rapid weight loss. Liver function tests are normal, erythrocyte sedimentation rate is accelerated and LDH progressively increases during the hospitalization. Imaging studies (ultrasound, CT scan, nuclear magnetic resonance) show a multilobued mass of around 12 cm of diameter in the right hepatic lobe. Tumoral and virological markers are negative. The pathology of an echo-guided biopsy informs a massive infiltration by a diffuse large B-cell lymphoma. The immunohistochemical study shows CD20+, CD45+ and negative CD3, CKAE1, AE3, Hepatocyte and HMB45. The citology of pleural liquid is negative for atypia, peripheral blood smear shows no signs of leukemia, bone marrow biopsy is negative for lymphomatous infiltration, and gallium scintigraphy and body CT scan do not reveal extrahepatic lesions. The patient starts chemotherapy with cyclophosphamide and methylprednisolone but worsens and dies two weeks after beginning treatment. We conclude that our patient had a rare disease with an unresectable lesion, poor prognostic factors and high recurrence risk. Chemotherapy is the treatment of choice in these cases.

  13. A case of multiple metastatic malignant melanoma with the largest lesion in the ileum and no skin lesion.

    PubMed

    Suzuki, Shuji; Watanabe, Shoichi; Kato, Hiroshi; Hattori, Hideo; Morita, Akimichi

    2012-12-01

    We report the case of a 72-year-old woman with malignant melanoma and multiple metastases; the largest tumor was in the ileum. The patient experienced general fatigue and bloody feces for 1 month before consulting a nearby clinic. Blood tests revealed anemia, and fecal occult blood was positive, but no abnormalities were detected using gastrointestinal endoscopy and colonoscopy or the skin of the entire body. Computed tomography images of the chest, abdomen, and pelvic region, and positron emission tomography-computed tomography images of the entire body revealed multiple nodules in the ileum, left mammary gland, left thyroid, right inguinal lymph node, and on the fascia of the right thoracic area and right buttocks. The tumor in the left mammary gland was excised and immunohistochemical analysis revealed that the excised tissue was positive for HMB45, melan-A, and MITF, but negative for S-100 protein. Diagnosed with melanoma with multiple metastases, the patient underwent four cycles of dacarbazine, nimustine hydrochloride, and vincristine (DAV) plus interferon beta chemotherapy and one cycle of dacarbazine, nimustine hydrochloride, cisplatin, and tamoxifen (DAC-Tam) chemotherapy. Two series of embolizations of the artery feeding the ileum tumors, as well as a series of plasma and red blood cell transfusions, were performed for ileum tumor hemorrhage. The patient was hospitalized eight times, for a total of 204 days during the 1-year survival period before her death from respiratory failure.

  14. A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial.

    PubMed

    Gupta, Janesh K; Daniels, Jane P; Middleton, Lee J; Pattison, Helen M; Prileszky, Gail; Roberts, Tracy E; Sanghera, Sabina; Barton, Pelham; Gray, Richard; Kai, Joe

    2015-10-01

    Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena®, Bayer) compared with usual medical treatment, with exploration of women's perspectives on treatment. A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. Women who presented in primary care. A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced

  15. Natural transformation and phase variation modulation in Neisseria meningitidis.

    PubMed

    Alexander, Heather L; Richardson, Anthony R; Stojiljkovic, Igor

    2004-05-01

    Neisseria meningitidis has evolved the ability to control the expression-state of numerous genes by phase variation. It has been proposed that the process aids this human pathogen in coping with the diversity of microenvironments and host immune systems. Therefore, increased frequencies of phase variation may augment the organism's adaptability and virulence. In this study, we found that DNA derived from various neisserial co-colonizers of the human nasopharynx increased N. meningitidis switching frequencies, indicating that heterologous neisserial DNA modulates phase variation in a transformation-dependent manner. In order to determine whether the effect of heterologous DNA was specific to the Hb receptor, HmbR, we constructed a Universal Rates of Switching cassette (UROS). With this cassette, we demonstrated that heterologous DNA positively affects phase variation throughout the meningococcal genome, as UROS phase variation frequencies were also increased in the presence of neisserial DNA. Overexpressing components of the neisserial mismatch repair system partially alleviated DNA-induced changes in phase variation frequencies, thus implicating mismatch repair titration as a cause of these transformation-dependent increases in switching. The DNA-dependent effect on phase variation was transient and may serve as a mechanism for meningococcal genetic variability that avoids the fitness costs encountered by global mutators.

  16. Hashimoto's thyroiditis could be secondary to vitiligo: the possibility of antigen crossover and oxidative stress between the two diseases.

    PubMed

    Gong, Qingli; Li, Xue; Gong, Qixing; Zhu, Wenyuan; Song, Guoxin; Lu, Yan

    2016-05-01

    Autoimmune thyroid diseases (AITDs) are often accompanied by vitiligo, and the sera of patients with vitiligo often demonstrate increased frequencies of thyroid autoantibodies. In this study, we investigated the expression of melanocyte-associated antigens in tissues from patients with Hashimoto's thyroiditis (HT) without vitiligo using immunohistochemistry. Tissues of HT without vitiligo, as well as normal thyroid tissues, were both negative for the expression of NKI/beteb, gp100, tyrosinase-related protein 1 (TRP1), HMB-45 and S100, whereas they were positive for the expression of tyrosinase-related protein 2 (TRP2), lysosome-associated membrane protein 1 (LAMP1) and CD69. Tyrosinase (TYR) was only detected in tissues of HT, and levels of LAMP1 and CD69 were higher in tissues of HT than in normal thyroid tissues (p < 0.005). These results suggest the possibility of antigen crossover and oxidative stress between vitiligo and HT that might represent an immunological basis for secondary HT associated with vitiligo.

  17. Infiltrating hybrid mesenchymal tumor of skeletal muscle showing lipomatous, hemangiomatous, leiomyomatous and osseous features - An unusual soft tissue tumor providing insight into the pathogenesis of lipoma variants.

    PubMed

    Chow, Louis Tsun Cheung

    2015-06-01

    Infiltrating angiolipoma and osteolipoma of the hand are rare. A 40-year-old man presented with slowly enlarging swelling of his right hand for two and half years without functional deficit but it became painful with slight limitation of movement for the past few months. Plain radiograph showed a large soft tissue swelling with specks of calcifications. Ultrasonography and magnetic resonance imaging revealed an infiltrative mass in the right palm deep to the flexor tendons. As biopsy suggested infiltrative angiolipoma of skeletal muscle, debulking of the tumor was performed. The tumor showed coexistence of all four mesenchymal elements, fat, blood vessel, smooth muscle and bone in various combinations in the form of angiolipomatous, osteolipomatous, ossified intramuscular hemangiomatous, myolipomatous and angiomyolipomatous patterns throughout the entire tumor. Small meningothelial-like whorls of spindle cells were focally seen, some showed intramembranous ossification forming small woven bony spicules in their centers. There were no atypical cells or lipoblasts. Staining for CDK4, MDM2, p16, HMB45 and Melan A was negative. The diagnosis was "infiltrating hybrid mesenchymal tumor of skeletal muscle showing lipomatous, hemangiomatous, leiomyomatous and osseous features". The fairly even admixture of the various components supports the neoplastic participation of each individual element. Hybrid mesenchymal tumor most probably originates from multipotent neoplastic cells showing multidirectional differentiation.

  18. Histologic differentiation of desmoplastic melanoma from cicatrices.

    PubMed

    Kaneishi, N K; Cockerell, C J

    1998-04-01

    Desmoplastic malignant melanoma (DMM) is a rare variant of melanoma that can be very difficult to diagnose correctly both clinically and histologically. The problem is compounded by the fact that many lesions persist at previous biopsy or excision sites so that scar tissue is often present admixed with or adjacent to the spindle cell neoplasm which may exhibit fibroblastic differentiation itself. In order to assess this problem, we compared and contrasted the histologic features of six DMM with 15 examples of cicatrices from various sources. Mature scars were readily differentiated from DMM by light microscopy. In contrast, immature scar and DMM had many features in common including hypercellularity, nodular lymphoid infiltrates, myxoid stroma, and atypical nuclei. The presence of a melanocytic proliferation within the epidermis above the dermal component, neurotropism, and S-100 and/or HMB-45 positivity of neoplastic cells were the only features that permitted reliable differentiation between the two. Clinical correlation and review of previous biopsy specimens are crucial in preventing a delayed diagnosis of DMM. Re-excision is advised in all questionable cases.

  19. Adrenal oncocytic phaeochromocytoma with putative adverse histologic features: a unique case report and review of the literature.

    PubMed

    Kasem, Kais; Lam, Alfred K-Y

    2014-12-01

    Oncocytic phaeochromocytomas are exceedingly rare tumours. To date, there are three reported cases in the literature. This report describes a case of adrenal oncocytic phaeochromocytoma with unique features and malignant potential in a 68-year-old man. The patient presented with an incidental non-functional mass discovered on routine radiological investigation, which was subsequently excised. Histologically, the tumour cells showed oncocytic features with high-grade nuclear abnormalities and foci of extension to the peri-adrenal fat. Immunohistochemistry performed was positive for chromogranin, CD56, S-100 and p53 and negative for inhibin, HMB-45, EMA, AE1/AE3, Cam 5.2 and calretinin. Electron microscopy showed electron dense granules of neurosecretory type, which confirmed the diagnosis. The malignant potential of the tumour was assessed on available histologic scoring systems, which demonstrated a high malignant potential. However, no recurrence was detected after 5 years of follow-up. Compared to all the previously reported cases of oncocytic phaeochromocytoma, this patient was the oldest on presentation, was the only case with identified high malignant potential and has the longest follow-up. A review of the literature showed that all the oncocytic phaeochromocytomas reported were non-functional, non-metastasizing and were described in women. To conclude, oncocytic phaeochromocytoma should be in the differential diagnoses of oncocytic tumours of the adrenal gland. Additional studies are needed to predict the behaviour of this entity.

  20. Synthesis, Structure, and Anticancer Activity of Arene-Ruthenium(II) Complexes with Acylpyrazolones Bearing Aliphatic Groups in the Acyl Moiety.

    PubMed

    Palmucci, Jessica; Marchetti, Fabio; Pettinari, Riccardo; Pettinari, Claudio; Scopelliti, Rosario; Riedel, Tina; Therrien, Bruno; Galindo, Agustin; Dyson, Paul J

    2016-11-21

    A series of neutral ruthenium(II) arene complexes [(arene)Ru(Q(R))Cl] (arene = p-cymene (cym) or hexamethylbenzene (hmb)) containing 4-acyl-5-pyrazolonate Q(R) ligands with different electronic and steric substituents (R = 4-cyclohexyl, 4-stearoyl, or 4-adamantyl) and related ionic complexes [(arene)Ru(Q(R))(PTA)][PF6] (PTA = 1,3,5-triaza-7-phosphaadamantane) were synthesized and characterized by spectroscopy (IR, UV-vis, ESI-MS, and (1)H and (13)C NMR), elemental analysis, X-ray crystallography, and density functional theory studies. The cytotoxicity of the proligands and metal complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR), as well as against nontumorous human embryonic kidney (HEK293) cells. In general the cationic PTA-containing complexes are more cytotoxic than their neutral precursors with a chloride ligand in place of the PTA. Moreover, the complexes do not show cross-resistance and are essentially equally cytotoxic to both the A2780 and A2780cisR cell lines, although they only show limited selectivity toward the cancer cell lines.

  1. Cytological aspects of melanotic variant of medullary thyroid carcinoma.

    PubMed

    de Lima, M A; Dias Medeiros, J; Rodrigues Da Cunha, L; de Cássia Caldas Pessôa, R; Silveira Tavares, F; de Fátima Borges, M; Marinho, E O

    2001-03-01

    We had the opportunity to examine a case of fine-needle aspiration (FNA) of a melanotic variant of medullary thyroid carcinoma (MTC) in a 20-yr-old man. The patient presented a single node, hardened and mobile upon deglutition, in the right lobe of the thyroid, for 9 mo, without symptoms of glandular dysfunction. Calcitonin (138 pg/ml), urinary calcium (177 mg/dl), and the carcinoembryonic antigen (341 ng/ml) were increased. The nodular aspirate, drawn by FNA, was represented by pleomorphic cells, with frequent intranuclear cytoplasmic inclusions, sometimes bi- or multinucleated, with abundant, finely granular cytoplasm, sometimes containing a brown pigment resembling melanin. An immunohistochemical study using monoclonal antibodies (Dako Corp., Carpinteria, CA) showed that the neoplastic cells were intensely and diffusely positive for calcitonin and chromogranin, and focally positive for HMB45. In view of these findings, the case was characterized as a melanotic variant of medullary carcinoma, a rare type of neoplasia, but having a prognosis similar to the classical variant of MTC.

  2. Benign myoepithelioma of the lung - a case report and review of the literature.

    PubMed

    Kourda, Jihene; Ismail, Olfa; Smati, Bel Hssan; Ayadi, Aida; Kilani, Tarek; El Mezni, Faouzi

    2010-01-13

    Benign myoepithelioma is extremely rare in the lung, to the best of our knowledge; only five cases have been reported in the literature. An 18-years woman complained from tiredness and fever during four months. Laboratory findings and fibroscopies were normal. CT of the thorax demonstrated a nodule in the left segment of the Fowler. Left inferior lobectomy was performed comporting a firm nodule of 25 mm, lifting the bronchial mucous membrane. Histologically, there was a proliferation of small cells of a plasmocytoid-type, with a predominantly whorled pattern. No mitotic activity or necrosis was seen in the tumor. Immuhistochemically, the tumor cells positive for smooth muscle actin, vimentine, and S100 protein. They were negatives for cytokeratine, chromogranine and HMB45. The diagnosis of benign myoepithelioma of the lung is so confirmed. The patient recovered well at 6 months follow-up. Benign myoepithelioma is a rare pulmonary neoplasm distinct from pleomorphic adenoma, which should be considered in the differential diagnosis of lung nodules.

  3. Benign myoepithelioma of the lung - a case report and review of the literature

    PubMed Central

    2010-01-01

    Introduction Benign myoepithelioma is extremely rare in the lung, to the best of our knowledge; only five cases have been reported in the literature. Case Report An 18-years woman complained from tiredness and fever during four months. Laboratory findings and fibroscopies were normal. CT of the thorax demonstrated a nodule in the left segment of the Fowler. Left inferior lobectomy was performed comporting a firm nodule of 25 mm, lifting the bronchial mucous membrane. Histologically, there was a proliferation of small cells of a plasmocytoid-type, with a predominantly whorled pattern. No mitotic activity or necrosis was seen in the tumor. Immuhistochemically, the tumor cells positive for smooth muscle actin, vimentine, and S100 protein. They were negatives for cytokeratine, chromogranine and HMB45. The diagnosis of benign myoepithelioma of the lung is so confirmed. The patient recovered well at 6 months follow-up. Conclusion Benign myoepithelioma is a rare pulmonary neoplasm distinct from pleomorphic adenoma, which should be considered in the differential diagnosis of lung nodules. PMID:20180958

  4. Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor.

    PubMed

    Fang, Chia-Lang; Lin, Yun-Ho; Chen, Wei-Yu

    2012-09-03

    Perivascular epithelioid cell (PEC) tumors (PEComas) are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643.

  5. Positive and negative quenches induced excitation dynamics for ultracold bosons in one-dimensional lattices

    NASA Astrophysics Data System (ADS)

    Mistakidis, Simeon; Cao, Lushuai; Schmelcher, Peter

    2015-05-01

    The correlated non-equilibrium dynamics of few-boson systems in one-dimensional finite lattices is investigated. Focusing on the low-lying modes of the finite lattice we observe the emergence of density-wave tunneling, breathing and cradle-like processes. In particular, the tunneling induced by the quench leads to a global density-wave oscillation. The resulting breathing and cradle modes are inherent to the local intrawell dynamics and related to excited-band states. Positive interaction quenches couple the density-wave and the cradle modes allowing for resonance phenomena. Moreover, the cradle mode is associated with the initial delocalization and following a negative interaction quench can be excited for setups with filling larger than unity. For subunit fillings it can be accessed with the aid of a negative quench of the lattice depth. Finally, our results shed light to possible controlling schemes for the cradle and the breathing modes. The evolution of the system is obtained numerically using the ab-initio multi-layer multi-configuration time-dependent Hartree method for bosons. (1)Hamburgisches Gesetz zur Förderung des wissenschaftlichen und künstlerischen Nachwuchses (HmbNFG), (2,3) Deutsche Forschungsgemeinschaft (DFG).

  6. Solitary metastatic cancer to the thyroid: a report of five cases with fine-needle aspiration cytology

    PubMed Central

    Lee, Mark W; Batoroev, Yuri K; Odashiro, Alexandre N; Nguyen, Gia-Khanh

    2007-01-01

    Three men and 2 women with ages ranging from 37 to 70 years, clinically and histologically confirmed solitary, palpable metastatic cancers to the thyroid (SMCT) and preoperative cytologic investigation of their thyroid lesions by fine-needle aspiration (FNA), were reviewed. Four patients were known to have a solid cancer treated by radical surgery 1 to 4 years prior [1 bronchogenic squamous cell carcinoma, 1 parotid adenoid cystic carcinoma, 1 renal cell carcinoma (RCC) and 1 cutaneous melanoma], and 1 patient had no past history of cancer. Direct smears prepared from the patients' thyroid FNAs were fixed in 95% ethanol and stained with the Papanicolaou method. In 3 cases, immunostaining of the aspirated tumor cells with thyroglobulin antibody was performed, and in 1 case an aspiration smear was stained with commercial HMB-45 antibody. A correct cytodiagnosis of metastatic cancer to the thyroid was made in all 5 cases. In 1 patient the thyroid FNA revealed a metastatic RCC that led to the discovery of a clinically occult RCC. All 5 patients died of metastatic disease 27 to 40 months after surgical resection of their SMCTs. PMID:17263878

  7. Unusual sinonasal small-cell neoplasms following radiotherapy for bilateral retinoblastomas

    SciTech Connect

    Frierson, H.F. Jr.; Ross, G.W.; Stewart, F.M.; Newman, S.A.; Kelly, M.D. )

    1989-11-01

    Two patients developed sinonasal small-cell neoplasms that arose 22 years and 37 years, respectively, following radiotherapy for bilateral retinoblastomas. The tumors were composed of small cells with scant cytoplasm and had a few scattered Homer-Wright rosettes. Immunohistochemically, one tumor was positive for keratin (CAM 5.2 and AE1/AE3), epithelial membrane antigen, and neuron-specific enolase. The other neoplasm was immunoreactive for keratin (CAM 5.2 only) and neuron-specific enolase; it also had focal immunopositivity for S-100 protein, desmin, and muscle-specific actin. Both were negative for CEA, vimentin, melanocyte-specific antigen (HMB45), chromogranin A, synaptophysin, Leu-7, 200 kd neurofilament, and retinal S-antigen. Despite aggressive multimodal therapy, the patients died of metastatic tumor 7 months and 10 months following their initial diagnosis, respectively. Although osteosarcoma is the most frequent second cancer following bilateral retinoblastomas, some patients develop clinically aggressive sinonasal small-cell tumors that are difficult to place into conventional classifications. Both of our cases showed evidence of multidirectional differentiation; one tumor labeled with epithelial and neural markers, and the other expressed epithelial, neural, and myogenous antigens.49 references.

  8. Reverse polarity capillary zone electrophoresis analysis of nitrate and nitrite in natural water samples

    SciTech Connect

    Metcalf, S.G.

    1998-06-11

    This paper describes the application of reverse polarity capillary zone electrophoresis (RPCE) for rapid and accurate determination of nitrate and nitrite in natural water samples. Using hexamethonium bromide (HMB) as an electroosmotic flow modifier in a borate buffer at pH 9.2, the resolution of nitrate and nitrite was accomplished in less than 3 minutes. RPCE was compared with ion chromatographic (IC) and cadmium reduction flow injection analysis (Cd-FIA) methods which are the two most commonly used standard methods for the analysis of natural water samples for nitrate and nitrite. When compared with the ion chromatographic method for the determination of nitrate and nitrite, RPCE reduced analysis time, decreased detection limits by a factor of 10, cut laboratory wastes by more than two orders of magnitude, and eliminated interferences commonly associated with IC. When compared with the cadmium reduction method, RPCE had the advantage of simultaneous determination of nitrate and nitrite, could be used in the presence of various metallic ions that normally interfere in cadmium reduction, and decreased detection limits by a factor of 10.

  9. Medications affecting functional status in older persons.

    PubMed

    Corsonello, Andrea; Onder, Graziano; Maggio, Marcello; Corica, Francesco; Lattanzio, Fabrizia

    2014-01-01

    Current evidence suggests that functional status is an important outcome of pharmacologic treatments in older people. At the moment, studies have shown diverse effects of medications on functional status. For example, some have shown potentially detrimental effects, while others have found improvements on physical function in elders. Overall, suboptimal prescribing and the occurrence of adverse drug reactions (ADRs) may negatively affect functional status. The use of selected drugs acting on central nervous system (CNS), e.g. benzodiazepines and antipsychotics, is generally associated with an increased risk of functional decline. The greater sensitivity of older people to these drugs, together with age-related changes in pharmacokinetics and pharmacodynamics, account for the observed detrimental effect and suggests a cautious approach to older and frail patients when prescribing CNS agents. On the other hand, selected drugs may slow or delay functional decline in older people. In particular, drugs aimed at targeting sarcopenia (loss in muscle mass and strength), such as testosterone in androgen deficiency, ACE-inhibitors, vitamin D and β-hydroxy β-methyl butyrate (HMB), as well as the recently developed selective androgen receptor modulators (SARMs) may hold extreme importance. This review will provide available evidence of the diverse impacts of drug medications on functional status in older persons.

  10. [Primary renal angiosarcoma].

    PubMed

    Costero-Barrios, Cesáreo B; Oros-Ovalle, Cuauhtémoc

    2004-01-01

    The twenty-fourth case of primary renal angiosarcoma is described, according to the available international literature, this present in a 71-year-old male, a mechanic by trade, without carcinogenic antecedents. Hematuria, pain in flank, and left-side tumoral mass of approximately 20 cm in diameter located in kidney by computerized axial tomography (CT) constituted manifestations. A left nefrectomy was performed. No metastasis was found. The tumor replaced 4/5 of the organ and weighed 1145 g. It showed angiomatous structure with atypical proliferation of endothelial cells in a sinusoldal trauma and anastomosatic vascular channels that invaded neighboring parenchymal and capsule. Tymorous cells were positive for CD31 and CD34 and negative for cytokeratins, S100 and HMB 45 proteins. The patient was subjected to treatment with chemotherapy and radiotherapy (lineal accelerator), but 12 months after surgery he presented retroperitonal tumoral relapse and hepatic metastasis. Diagnostic differentiation with benign vascular tumors is pointed out, as well as carcinomas and sarcomas that showed an outstanding angiomatous component, both primary and/or secondary. Primary renal angiosarcoma exposes the multiplicity of localizations that it is capable of with a tumor of this type, as well as renal parenquimatous capacity to be the seat of a great variety of neoplasias.

  11. Prognostic impact of tumour burden measured by quantitative real-time PCR from sentinel lymph nodes of melanoma patients: data from 10-year follow-up.

    PubMed

    Eigentler, Thomas Kurt; Hinderer, Joachim; Noor, Seema; Garbe, Claus; Leiter, Ulrike

    2017-04-01

    Sentinel node (SN) biopsy is regarded as standard of care for patients (pts) with cutaneous melanoma ≥1.0 mm of thickness. In the recent AJCC classification, findings in the SN are simply classified as positive or negative. In our analyses, we were interested whether quantitative real-time PCR (qRT-PCR) is able to predict disease-free survival (DFS) and overall survival (OS) depending on tumour burden in the SN. One hundred and forty-five pts were analysed using qRT-PCR for tyrosinase. Results were analysed using accelerated failure time survival model and cox proportional hazards models using the R statistics framework. Forty-one pts (28%) were positive according to qRT-PCR. In total, 12 of 41 pts showed tumour deposits in the SN using S100 and/or HMB-45-labelled immunohistochemistry as well. One patient had micrometastases detected by immunohistochemistry staining but failed in the qRT-PCR. After 10 years of follow-up, 34 patients recurred and 27 patients died. Significant differences for DFS and OS were detected for sex, increasing tumour thickness, ulceration of the primary tumour, and metastatic spread in the SN determined by histology as well as qRT-PCR. Quantitative analyses showed a logarithmic correlation between tumour burden and prognosis. However, as multivariate analyses reveal qRT-PCR was not superior compared to classical histology or immunohistology.

  12. Extramedullary plasmacytoma associated with an ectopic tooth in the nasal cavity.

    PubMed

    Zhang, Yi; Xu, Yong; Xu, Yu; Tao, Zezhang

    2015-01-01

    Extramedullary plasmacytoma and tooth eruption into the nasal cavity are both rare events. We report a case of plasmacytoma associated with an ectopic tooth. To the best of our knowledge, such a case has not been previously reported in the literature. A 63-year-old woman presented for evaluation of an 8-month history of a bloody nasal discharge from the posterior naris. Nasal endoscopy detected a slight eminence approximately 0.5 cm in diameter in the right nasal floor. Computed tomography demonstrated a tooth-like, high-attenuation shadow. A biopsy identified chronic inflammation of the mucosa and tissue. A diagnosis of an ectopic tooth in the right nasal cavity was initially considered. The mass and the tooth-like neoplasm were removed via nasal endoscopy. Immunohistochemistry of the excised mucosa showed strong positivity for kappa light chains, positivity for leukocyte common antigen and CD138, and negativity for lambda light chains, epithelial membrane antigen, CD1, and HMB-45. The final diagnosis was an extramedullary plasmacytoma in the right nasal cavity associated with an ectopic tooth. No bone metastasis was observed. Definitive radiotherapy was performed after the operation. During 40 months of follow-up, the patient exhibited no evidence of local recurrence or metastasis. The diagnosis in this case was made difficult by the nonspecific clinical manifestations, the presence of the ectopic tooth, and incorrect interpretation of preoperative histopathology. Physicians should maintain a clinical suspicion for the possibility that an ectopic tooth might be associated with a tumor.

  13. [Vaginal Follicular dendritic cell sarcoma in patient with previous urinary tract carcinoma. Case Report].

    PubMed

    Zaya, Alejandro Martin; González, Ana Carolina; Sandrone, Silvana S; Sambuelli, Ruben Horacio

    2016-01-01

    follicular dendritic cell sarcoma (FDC sarcoma) is an uncommon neoplasm derived from FDC present in lymphoid follicles. It usually presents in lymph nodes, being extranodal location a very unusual event. A 78 year old female, with prior left nephrectomy for invasive urothelial carcinoma, consulted for genitorragia. At examination, a polypoid vaginal lesion, measuring 3.5 cm in diameter was discovered. It was reported as squamous cell carcinoma in incisional biopsy. A polipectomy was performed. Examination of resected specimen showed a tumor having pushing edges, arranged in a solid pattern with spindle and epithelioid cells, having a syncytial appearance, diffusely sprinkled with numerous lymphocytes and granulocytes. At immunohistochemistry neoplastic cells were positive for vimentin, CD 68, CD 21 and fascine, and focally positive for S-100 and CD45. Occasional scattered neoplastic cells expressed CD30 and CD 23. They were negative for CD3, CD20, myeloperoxidase, AE1 / AE3, EMA, HMB45, Melan A, desmin, Chromogranin, CD1a and CD35. Infiltrating lymphocites were mainly of T cell lineage (CD3 +). We report a case of FDC sarcoma in an unusual location, being to our knowledge, the first one at this site. The fact of having a prior neoplasia posed additional difficulties in differential diagnosis. Histological findings with expression of a specific marker of FDC (in this case CD21) allowed us to establish an accurate diagnosis.

  14. Interaction Quench Induced Multimode Dynamics of Finite Atomic Ensembles

    NASA Astrophysics Data System (ADS)

    Mistakidis, Simeon; Cao, Lushuai; Schmelcher, Peter

    2015-05-01

    The correlated non-equilibrium dynamics of few-boson systems in one-dimensional finite lattices is investigated. Starting from weak interactions we perform a sudden interaction quench and employ the numerically exact Multi-Layer Multi-Configuration time-dependent Hartree method for bosons to obtain the resulting quantum dynamics. Focusing on the low-lying modes of the finite lattice we observe the emergence of density-wave tunneling, breathing and cradle-like processes. In particular, the tunneling induced by the quench leads to a ``global'' density-wave oscillation. The resulting breathing and cradle modes are inherent to the local intrawell dynamics and connected to excited-band states. Moreover, the interaction quenches couple the density-wave and the cradle modes allowing for resonance phenomena. These are associated with an avoided-crossing in the respective frequency spectrum and lead to a beating dynamics for the cradle. Hamburgisches Gesetz zur Förderung des wissenschaftlichen und künstlerischen Nachwuchses (HmbNFG).

  15. Primary malignant neuroectodermal tumor of the ileum with predominantly uncommon pseudopapillary architecture.

    PubMed

    Zhao, Zhihua; Zhang, Dandan; Li, Wencai; Zhang, Lan; Li, Zhen; Zhou, Jun

    2014-01-01

    A malignant gastrointestinal neuroectodermal tumor (GNET), a distinctive entity covering the characteristics of clear cell sarcoma (CCS) of gastrointestinal tract described recently, arising primarily in the ileum of a 33-year-old woman is reported. Histologically, the neoplasm involved the full thickness of the intestinal wall. Tumor cells, mainly displayed epithelioid or polygonal appearance with oval or round nuclei, arranged in strand, nested, and solid pattern with prominent pseudopapillary architecture instead of the familiar histological image with multinucleated osteoclast-like giant cells. They were positive for vimentin, S-100, synaptophysin, CD56 and CD99 protein, but negative for AE1/AE3, EMA, CEA, LCA, Desmin, CK7, CK20, Villin, CgA, CD117, Dog-1, GFAP, Melan-A, HMB-45, CD34, CR, WT1, D2-40. Fluorescence in situ hybridization (FISH) showed the presence of chromosomal translocation involving EWSR. The patients lived through a calm period after a tumor resection and 4 cycles of chemotherapy combining ifosfamide and epirubicin. This case demonstrates that GNET is a rare tumor in gastrointestinal tract, and furthermore, various misleading histological characteristics should been taken into consideration in the diagnosis.

  16. Esophageal subepithelial lesion diagnosed as malignant gastrointestinal neuroectodermal tumor.

    PubMed

    Kim, Sung Bum; Lee, Si Hyung; Gu, Mi Jin

    2015-05-14

    A 21-year-old male visited our hospital with a complaint of aggravating dysphagia and odynophagia for a few days. Esophagogastroduodenoscopy showed huge bulging mucosa with an intact surface causing luminal narrowing at 35 cm from the incisor teeth. Endoscopic ultrasonography showed an about 35 mm sized irregular margined in-homogenous hypoechoic lesion with an obscure layer of origin. Endoscopic ultrasonography fine needle aspiration revealed spindle cell proliferation without immunoreactivity for CD117, SMA, and cytokeratin. The patient underwent excision of the subepithelial lesion at the distal esophagus. On pathologic examination of the specimen, the tumor was composed of short fascicles of oval to spindle cells with eosinophilic and clear cytoplasm and vesicular nuclei. The tumor cells were positive for S-100 and SOX10 and negative for CD117, SMA, HMB-45, melan-A, cytokeratin, and CD99. The split-apart signal was detected in EWSR1 on FISH, suggesting a malignant gastrointestinal neuroectodermal tumor. At the time of writing, the patient is on radiation therapy at the operated site of esophagus and doing well, with no recurrence for three months. Malignant gastrointestinal neuroectodermal tumor is a rare gastrointestinal tumor with features of clear cell sarcoma, without melanocytic differentiation, and shows a poor prognosis. This is the first reported case of malignant gastrointestinal neuroectodermal tumor arising as subepithelial lesion in the esophagus.

  17. Squamomelanocytic tumor: a new case of a unique biphenotypic neoplasm of uncertain biological potential.

    PubMed

    Rongioletti, Franco; Baldari, Manuela; Carli, Carla; Fiocca, Roberto

    2009-04-01

    Squamomelanocytic tumor is an uncommon cutaneous neoplasm composed of an admixture of melanocytic and squamous cellular phenotypes. We describe a case of this tumor in a 94-year-old man who presented with a nodule on the back. Histologically, a well-demarcated expansive dermal nodule was composed of anastomosing epithelial strands with focal formation of squamous pearls and ductal structures commixed with elongated spindle cells with clear cytoplasm grouped in nests. The two cell types were diffusely admixed or clustered in groups within the nodule. Immunohistochemical studies showed that the spindle cells grouped in nests expressed S-100 and HMB-45 antigens, and the squamoid cells expressed cytokeratins and carcinoembrionic antigen (CEA) protein only in the inner layer of the ducts and the cystic space. Atypical features and high mitotic activity was observed in the melanocytic cells but slight atypia, mild dyskeratosis and mitotic figures were observed also in the squamoid component. This tumor represents a proliferation of two phenotypic cells that are distinctive for their intimate admixture and singular immunohistochemical profile. The authors discuss the histogenesis of this tumor, suggesting that it could represent an atypical solid-cystic hidradenoma colonized by a melanocytic malignant component. The biological behavior of this neoplasm remains currently uncertain.

  18. Inflammatory angiomyolipoma of the liver: a rare hepatic tumor

    PubMed Central

    2012-01-01

    Angiomyolipoma (AML) is a rare mesenchymal neoplasm of the tumor, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle and adipose cells. Hepatic AML may demonstrate a marked histological diversity. We herein present one case of hepatic AML exhibiting prominent inflammatory cells in the background, which happened in a 61-year-old Chinese female patient, without signs of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background, including small lymphocytes, plasma cells, and eosnophils. The tumor cells were spindled and histiocytoid in shape, with slightly eosinophilic cytoplasm, and arranged along the vessels or scattered among the inflammatory background. Sinusoid structure was obviously seen in the tumor. Mature adipocytes and thick-walled blood vessels were focally observed at the boundaries between the tumor and surrounding liver tissues. The tumor cells were positive immunostaining for HMB-45, Melan-A, and smooth muscle actin. The inflammatory AML should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor and deserves wider recognition for its occurrence as a primary hepatic tumor. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1828633072762370 PMID:22978636

  19. Comparative evaluation of diode laser ablation and surgical stripping technique for gingival depigmentation: A clinical and immunohistochemical study.

    PubMed

    Bakutra, Gaurav; Shankarapillai, Rajesh; Mathur, Lalit; Manohar, Balaji

    2017-01-01

    There are various treatment modalities to remove the black patches of melanin pigmentation. The aim of the study is to clinically compare the diode laser ablation and surgical stripping technique for gingival depigmentation and to evaluate their effect on the histological changes in melanocyte activity. A total of 40 sites of 20 patients with bilateral melanin hyperpigmentation were treated with the surgical stripping and diode laser ablation technique. Change in Hedin index score, change in area of pigmentation using image analyzing software, pain perception, patient preference of treatment were recorded. All 40 sites were selected for immunohistochemical analysis using HMB-45 immunohistochemical marker. At 12 months post-operative visit, in all sites, repigmentation was observed with different grades of Hedin index. Paired t-test, analysis of variance, and Chi-square tests were used for statistical analysis. Repigmentation in surgical stripping is significantly lesser compared to laser ablation. Lesser numbers of melanocytes were found on immunohistological examination at 12 months postoperatively. Comparison for patient preference and pain indices give statistically significant values for diode laser techniques. Gingival hyperpigmentation is effectively managed by diode laser ablation technique and surgical stripping method. In this study, surgical stripping technique found to be better compared to diode laser ablation.

  20. Impact of protein concentration on the determination of thiolic groups of ovalbumin: a size exclusion chromatography-chemical vapor generation-atomic fluorescence spectrometry study via mercury labeling.

    PubMed

    Campanella, Beatrice; Onor, Massimo; D'Ulivo, Alessandro; Giannarelli, Stefania; Bramanti, Emilia

    2014-02-18

    We optimized a hyphenated system based on size exclusion chromatography coupled to a microwave/UV mercury oxidation system and an atomic fluorescence detector (SEC-CVG-AFS) for the online oxidation of free and protein-complexed p-hydroxymercuribenzoic acid (pHMB) without the employment of chemical oxidizing agents. This system has been applied to the study of labeling of thiolic groups of native ovalbumin (OVA) as a function of protein concentration. We found that the protein concentration strongly affects the species distribution of OVA, the number of thiolic groups titrated in each species, and thus, the accuracy in the determination of the total number of thiolic groups. The amount of titrated sulfhydryl groups in the protein concentration range investigated (5-100 μmol L(-1)) varied from 2.40 ± 0.01 to 1.85 ± 0.05 for the monomeric form of OVA and from 4.63 ± 0.01 to 5.63 ± 0.05 for the total OVA, which represents more than four theoretical number of reduced Cys. This information is important from the analytical point of view because it suggests that, unless to operate with diluted concentration of protein, the number of titrated thiolic groups results from both the aspecific interaction of the probe with aggregates species and to the specific bond of the probe with the accessible -SH groups.

  1. Computer modelling of dynamics of Ser92X deoxymyoglobin mutants.

    PubMed

    Nowak, W

    1998-01-01

    The hydrogen bond between His93 and Ser92, recently discovered in crystal structures of myoglobins (Mbs), may contribute to the oxygen storage capacity of the heme proteins through a stabilization of the proximal ligand. The possible influence of this H-bond on the geometry of the heme proximal side and ligand binding properties of Mb were computationally studied using model proteins with point mutations affecting this bond. The results of the computer modelling of Ser92X (X = Ala, Ile, Thr, Val) mutants of human (H) and sperm whale (SW) Mbs are presented. The OPLS-AMBER-CHARMM forcefield was used in the calculations. Several 10-50 ps molecular dynamics simulations (300 K, in vacuo) were performed. Our results show that the Ser92X mutants are stable molecules. In the wild types and Ser92Thr mutants, the H-bond studied is observed only for a relatively short period of time. It is expected that in both HMb and SW Mb molecules the impact of the proximal histidine interaction with the Ser92(F7) residue on the iron reactivity is rather low. However, the limited torsional flexibility of the proximal histidine imidazole ring was found in hydrogen bonding mutants. This effect may be attributed to the specific long range electrostatic interactions.

  2. Treatment of an amelanotic melanoma using radiation therapy in a lesser Madagascar hedgehog tenrec (Echinops telfairi).

    PubMed

    Harrison, Tara M; Dominguez, Pedro; Hanzlik, Kim; Sikarskie, James G; Agnew, Dalen; Bergin, Ingrid; Fitzgerald, Scott D; Kitchell, Barbara E; McNiel, Elizabeth

    2010-03-01

    A 15-yr-old, male lesser Madagascar hedgehog tenrec (Echinops telfairi) presented with a mass caudal to the right ear. Cytology suggested a sarcoma. Surgical removal was attempted. Histology was consistent with a soft tissue sarcoma. The mass recurred within 331 days post operation. Radiation therapy was initiated. Computed tomography was used for staging in conjunction with three-dimensional computerized treatment planning software to permit accurate lesion localization and to optimize normal tissue sparing. A total dose of 6,480 cGy was administered in 24 fractions over 46 days. Transient hind limb paresis developed during the course of the radiation therapy, but resolved after 7 days with prednisone treatment. Minimal acute radiation toxicity was observed. The mass responded with at least a 90% reduction in volume following radiation treatment. The animal survived 266 days from the initiation of treatment. On necropsy, a small mass and granulation tissue were found at the site of the initial neoplasm, indicating good regional control of the tumor; however, extensive metastases to the spleen and liver were present. Immunohistochemically, the original, recurrent, and metastatic populations were strongly positive for HMB 45 and weakly positive for S-100, and the final diagnosis was metastatic amelanotic melanoma.

  3. Primary malignant melanoma of cervix and vagina

    PubMed Central

    Lee, Jae Hoon; Yun, Jisun; Seo, Jung-Won; Bae, Go-Eun; Lee, Jeong-Won

    2016-01-01

    Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The overall prognosis of melanomas of the female genital tract is very poor. Two cases of MM of the female genital tract are presented. The first case is of a 70-year-old female patient who complained of left thigh pain and underwent magnetic resonance imaging that showed cervical cancer with involvement of the vagina, bladder, and parametrium, in addition to multiple bony metastases of the proximal femur, acetabulum, and both iliac bones. The second case is of a 35-year-old female patient who suffered from vaginal bleeding for 5 months, and she was diagnosed as having primary vaginal melanoma. The patient underwent radical surgery and two additional surgeries because of recurrence of cancer in both inguinal areas. After surgery, the patient received adjuvant immunotherapy, radiation therapy, and chemotherapy. In both the aforementioned cases, the pathologic diagnosis was made after immunohistochemical analysis, i.e., the tumor cells were stained with HMB-45 and S100, and were found to be positive for both immunostains. PMID:27668208

  4. [Study on distribution and countermeasures of Oncomelania snails in beach wetlands of Runzhou section of lower reaches of Yangtze River].

    PubMed

    Xia, Ai; Huang, Yixin; Jiang, Jun; Zhou, Ya-Min; Hang, De-rong; Tao, Heng-ye

    2014-04-01

    To understand the distribution of the river beach wetlands and Oncomelania snails in the lower reaches of the Yangtze River, and explore the countermeasures of snail control. The river beach wetlands outside the Yangtze River levee were investigated and classified according to the hierarchical and classification system of wetlands of China. The snail survey was carried out in the beach wetlands of Runzhou section of lower reaches of the Yangtze River from 2004 to 2013. The change trend of snail areas and the densities was analyzed in the wetlands. The river beach of Runzhou section of lower reaches of the Yangtze River belongs to the riverine wetland. There was Oncomelania snail breeding except the permanent water area. At present, there were natural wetlands of 1303.0 hm2, human-made wetlands of 1479.0 hmb2 and wetland function changes of 1059.0 hm2 in the river beach of Runzhou section. There was the snail area of 181.4 hm2 in the natural wetland in 2013. The area of snail control by the molluscicide and environmental modification was 4624.55 hm2 from 2004 to 2013. The decline rates of snail areas and densities were 66.53% and 77.66% respectively. The existing Oncomelania snails were distributed in the natural wetlands. The human-made wetland is helpful to snail control. The snail control in the river beach wetlands should attach a great importance to the protection of wetland ecology.

  5. Cytologic Interpretation of Melanotic Neuroectodermal Tumour of Infancy Involving Cranial Bones: Clue to Diagnosis

    PubMed Central

    Biswal, Priyadarshini; Behera, Susmita; Dhal, Ipsita; Surabhi

    2015-01-01

    Melanotic neuroectodermal tumour of infancy (MNTI) is a rare, benign but locally aggressive neoplasm of infants commonly affecting the maxilla. It can also involve other areas like skull, mandible, brain and epididymis. The tumour comprise of dual populations of cells like small, basophilic neuroblast like cells and large pigment laden epithelial cells arranged in tubular and pseudoglandular pattern. The proportion of two components varies and therefore the diagnosis can be difficult in absence of the large cells. We describe the cytologic, histologic and immunohistochemical findings in a case of MNTI involving left side orbit with frontal, temporal and parietal bones. The cytologic interpretation could be made due to the suggestive clinical and radiologic findings and detection of large epithelial pigmented cells on thorough searching. The neuroblast like cells was positive for Neuron specific enolase, large cells for HMB-45 and Pan CK. Both the cellular components were negative for desmin. This case report is presented due to its rarity and also to aid the surgical pathologists in diagnosis where the findings are not too straight forward. PMID:26500916

  6. ORAL AMELANOTIC MELANOMA

    PubMed Central

    Adisa, A.O.; Olawole, W.O.; Sigbeku, O.F.

    2012-01-01

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases are amelanotic. No etiologic factors or risk factors have been recognized for oral melanomas. Some authors have suggested that oral habits and selfmedication may be of etiological significance. Oral melanoma is rare but it is relatively frequent in countries like Japan, Uganda, and India. It is rarely identified under the age of 20 years. In Australia where cutaneous melanomas are relatively common primary melanoma of the oral mucosa is rare. The surface architecture of oral melanomas ranges from macular to ulcerated and nodular. The lesion is said to be asymptomatic in the early stages but may become ulcerated and painful in advanced lesions. The diagnosis of amelanotic melanoma is more difficult than that of pigmented lesions. The neoplasm consists of spindle-shaped cells with many mitotic figures and no cytoplasmic melanin pigmentation. Immunohistochemistry using S-100, HMB-45, Melan-A and MART-1 will help in establishing the correct diagnosis. Radical surgery with ample margins and adjuvant chemotherapy are appropriate management protocol for malignant melanoma. Oral melanoma is associated with poor prognosis but its amelanotic variant has even worse prognosis because it exhibits a more aggressive biology and because of difficulty in diagnosis which leads to delayed treatment. PMID:25161399

  7. Non psammomatous melanocytic schwannoma presenting as a subcutaneous nodule: A rare presentation of a rare lesion

    PubMed Central

    Gulati, Harveen Kaur; Joshi, Avinash R.; Anand, Mani; Deshmukh, S. D.

    2016-01-01

    Melanocytic schwannoma (MS) is an extremely rare soft tissue tumor accounting for less than 1% of all primitive nerve sheath tumors, with a predilection for spinal nerve involvement. To date, only 20 cases of cutaneous/subcutaneous MS have been described in literature. Here, we describe a case of MS presenting as a subcutaneous nodule in a 22-year-old male in right thigh. On examination, the nodule measured 2.5 × 2.0 × 1.5 cm with overlying skin showing a bluish hue and an ulcer. With a preoperative diagnosis of hemangioma, the patient was taken up for wide local excision and was diagnosed as a case of non psammomatous melanocytic schwannoma based on clinical, histological, and immunohistochemical studies. Immunohistochemistry revealed positivity with S-100, HMB-45, and Melan A with pericellular Laminin positivity. Carney's syndrome was ruled out. MS needs to be differentiated from other pigmented lesions like pigmented neurofibroma, Bednar tumor, cellular blue neavus, and especially malignant melanoma, which has an obvious ominous prognosis. Since MS can show unpredictable behavior especially in absence of overt malignant features, a long term follow up with or without radiotherapy is recommended. PMID:27366278

  8. Bizarre stromal cells in the esophagus: report of 2 cases and literature review.

    PubMed

    Dhungel, Bal M; De Petris, Giovanni

    2013-08-01

    A significant mimicker of malignancy in the esophagus is the presence of atypical/bizarre stromal cells (BSCs). Two patients, a 60-year-old woman and a 59-year-old man, with esophageal polyps at the gastroesophageal junction showed highly atypical/bizarre cells in the polyps' stroma. BSCs were admixed with inflammatory cells and had large atypical nuclei, prominent nucleoli, and variably abundant amphophilic cytoplasm. Immunohistochemical studies showed that BSCs expressed vimentin whereas S-100, CD68, HMB45, CD45, Pan-cytokeratin, CK5/6, p63, CD10, EMA, MART-1, desmin, smooth muscle actin, CD31, CD34, and CMV were negative. Ki-67 showed low proliferative rate (less than 1% positivity). No evidence of intracellular mucin was found after histochemical stains (AB/PAS and mucicarmine). Follow-up endoscopic mucosal resection was available in both cases and showed benign esophageal mucosa and submucosa with disappearance, in one case, or marked decrease of BSCs. Esophageal BSCs reports in the literature invariably locate them in distal esophagus polyps or masses. Awareness of BSCs, of their location and associations, may help to prevent misdiagnosis of malignancy. The literature of esophageal BSCs is reviewed and the approach to this abnormality is discussed.

  9. Aerodynamic performance investigation on waverider with variable blunt radius in hypersonic flows

    NASA Astrophysics Data System (ADS)

    Li, Shibin; Wang, Zhenguo; Huang, Wei; Xu, Shenren; Yan, Li

    2017-08-01

    Waverider is an important candidate for the design of hypersonic vehicles. However, the ideal waverider cannot be manufactured because of its sharp leading edge, so the leading edge should be blunted. In the paper, the HMB solver and laminar flow model have been utilized to obtain the flow field properties around the blunt waverider with the freestream Mach number being 8.0, and several novel strategies have been suggested to improve the aerodynamic performance of blunt waverider. The numerical method has been validated against experimental data, and the Stanton number(St) of the predicted result has been analyzed. The obtained results show good agreement with the experimental data. Stmax decreases by 58% and L/D decreases by 8.2% when the blunt radius increases from 0.0002 m to 0.001 m. ;Variable blunt waverider; is a good compromise for aerodynamic performance and thermal insulation. The aero-heating characteristics are very sensitive to Rmax. The position of the smallest blunt radius has a great effect on the aerodynamic performance. In addition, the type of blunt leading edge has a great effect on the aero-heating characteristics when Rmax is fixed. Therefore, out of several designs, Type 4is the best way to achieve the good overall performance. The ;Variable blunt waverider; not only improves the aerodynamic performance, but also makes the aero-heating become evenly-distributed, leading to better aero-heating characteristics.

  10. Primary colonic melanoma presenting as ileocecal intussusception: case report and literature review.

    PubMed

    Li, Wen-Xiang; Wei, Ye; Jiang, Yi; Liu, Ya-Lan; Ren, Li; Zhong, Yun-Shi; Ye, Le-Chi; Zhu, De-Xiang; Niu, Wei-Xin; Qin, Xin-Yu; Xu, Jian-Min

    2014-07-28

    Primary malignant melanoma originating in the colon is an extremely rare disease. Herein, we report a case of primary melanoma of the ascending colon. The patient was a 57-year-old male who was admitted to our hospital for persistent abdominal pain and episodes of bloody stool, nausea and vomiting. A computed tomography scan revealed lower intestinal intussusception and enlarged lymph nodes in the abdominal cavity and retroperitoneum. During laparoscopic operation, multiple enlarged lymph nodes were found. Several segments of the proximal small intestine were incarcerated into the distal small intestine, forming an internal hernia and obstruction. The necrotic terminal ileum was invaginated into the ascending cecum. Subsequently, adhesive internal hernia reduction and palliative right hemicolectomy were performed. Pathologic examination of the excised specimen revealed a polypoid mass in the ascending colon. Histological examination showed epithelioid and spindle tumor cells with obvious cytoplasmic melanin deposition. Immunohistochemical staining revealed that the tumor cells were positive for S-100, HMB-45 and vimentin, confirming the diagnosis of melanoma. The patient history and a thorough postoperative investigation excluded the preexistence or coexistence of a primary lesion elsewhere in the skin, anus or oculus or at other sites. Thus, we consider our case to represent an aggressive primary colon melanoma presenting as ileocecal intussusception and intestinal obstruction.

  11. Primary colonic melanoma presenting as ileocecal intussusception: Case report and literature review

    PubMed Central

    Li, Wen-Xiang; Wei, Ye; Jiang, Yi; Liu, Ya-Lan; Ren, Li; Zhong, Yun-Shi; Ye, Le-Chi; Zhu, De-Xiang; Niu, Wei-Xin; Qin, Xin-Yu; Xu, Jian-Min

    2014-01-01

    Primary malignant melanoma originating in the colon is an extremely rare disease. Herein, we report a case of primary melanoma of the ascending colon. The patient was a 57-year-old male who was admitted to our hospital for persistent abdominal pain and episodes of bloody stool, nausea and vomiting. A computed tomography scan revealed lower intestinal intussusception and enlarged lymph nodes in the abdominal cavity and retroperitoneum. During laparoscopic operation, multiple enlarged lymph nodes were found. Several segments of the proximal small intestine were incarcerated into the distal small intestine, forming an internal hernia and obstruction. The necrotic terminal ileum was invaginated into the ascending cecum. Subsequently, adhesive internal hernia reduction and palliative right hemicolectomy were performed. Pathologic examination of the excised specimen revealed a polypoid mass in the ascending colon. Histological examination showed epithelioid and spindle tumor cells with obvious cytoplasmic melanin deposition. Immunohistochemical staining revealed that the tumor cells were positive for S-100, HMB-45 and vimentin, confirming the diagnosis of melanoma. The patient history and a thorough postoperative investigation excluded the preexistence or coexistence of a primary lesion elsewhere in the skin, anus or oculus or at other sites. Thus, we consider our case to represent an aggressive primary colon melanoma presenting as ileocecal intussusception and intestinal obstruction. PMID:25071362

  12. Diffuse hyperplastic mesothelial cells in multiple lymph nodes: case report with review of the literature

    PubMed Central

    Peng, Libo; Shen, Qin; Liu, Xia; Wang, Jiandong; Shi, Shanshan; Yu, Bo; Zhou, Xiaojun

    2013-01-01

    We report a case of diffuse hyperplastic mesothelial cells in multiple lymph nodes. Microscopically, the lymph nodes had a normal follicular pattern. The lymphatic sinus was extremely expanded, within the sinuses the epithelial-like cells proliferated actively in the form of sheets and clusters. Epithelioid-like cells had eosinophilic cytoplasm, prominent nucleoli and vesicular nuclei. Mitotic figures were rarely observed. These cells were immunopositive for Calretinin, CK5/6, D2-40, MC and Ckpan and immunonegative for S-100, HMB45, MelanA, TTF-1, CDX-2, Villin, ALK, CD30, CD20, CD3, CD1a and CD68. In addition, during a 22 months follow-up period failed to identify any malignant neoplasms, thus confirming the benign nature of these cells. It is the first reported case of diffuse hyperplastic of mesothelial cells mainly in the cervical lymph nodes associated with systemic multiple lymph node involvement. Awareness of this event is important for the pathologist in preventing the misdiagnosis of malignancy. PMID:23638225

  13. Signet-ring cell melanoma with sentinel lymph node metastasis: A case report with immunohistochemical analysis and review of the clinicopathological features

    PubMed Central

    ISHIDA, MITSUAKI; IWAI, MUNEO; YOSHIDA, KEIKO; KAGOTANI, AKIKO; OKABE, HIDETOSHI

    2014-01-01

    Signet-ring cell melanoma is an extremely rare variant of malignant melanoma. A 68-year-old male presented with a black nodule on the left thigh. Histopathological examination revealed proliferation of sheet-like or variable-sized nests of atypical melanocytes. Neoplastic cells showing signet-ring cell appearance, characterized by the presence of eccentrically located enlarged nuclei and abundant pale cytoplasm, were also present. Immunohistochemically, the tumor cells were positive for S-100 protein, vimentin and Melan-A. Moreover, mammalian target of rapamycin (mTOR) pathway proteins were diffusely expressed. The current case report presents the 21st reported case of signet-ring cell melanoma. Analyses of the clinicopathological features revealed that this disease commonly affects middle-aged males and the presence of metastatic signet-ring cell melanoma with an unknown primary tumor. Immunohistochemical analyses of melanocytic markers have been useful for establishing the diagnosis of this type of disease, however, HMB-45 is occasionally found to be negative. In addition, the present case report is the first to analyze the expression of mTOR pathway proteins, which are central proteins involved in carcinogenesis and its inhibitor has been proposed as a therapeutic target for various types of tumor. Therefore, the mTOR inhibitor may also be a potential candidate for the treatment of this type of tumor. PMID:24348822

  14. Primary uterine cervix melanoma resembling malignant peripheral nerve sheath tumor: a case report.

    PubMed

    Pusceddu, Sara; Bajetta, Emilio; Buzzoni, Roberto; Carcangiu, Maria Luisa; Platania, Marco; Del Vecchio, Michele; Ditto, Antonino

    2008-10-01

    A rare variant of malignant melanoma (MM) of the uterine cervix that mimics a malignant peripheral nerve sheath tumor (MPNST) is described. A 43-year-old white woman was admitted to the hospital complaining of genital discharge and vaginal bleeding. Neoadjuvant chemotherapy and total abdominal hysterectomy and bilateral salpingo-ovariectomy plus pelvic lymphadenectomy were performed, and the diagnosis was MPNST, FIGO IIB. Pathological examination showed a diffuse proliferation of amelanotic spindle cells and large, highly atypical, frequently multinucleated, bizarre, and S100-, HMB-45-, vimentin-positive cells. The patient remained disease-free for 43 months, when an abdominal computed tomographic scan showed local polypoid vaginal lesions, with histological features of typical MM. A pathological review was obtained in our institution by a gynecological pathologist, who defined the primary neoplasm in the cervix as an MM, with a pattern of growth histologically simulating an MPNST, metastatic to the vagina. To our knowledge, this is the first report in literature of MM of the uterine cervix resembling MPNST. Despite its rarity, this variant of MM should be considered when a diagnosis of cervix MPNST is made. The histological and immunohistochemical features of these different entities should be considered in the differential diagnosis.

  15. Determination of nitrate and nitrite in Hanford defense waste(HDW) by reverse polarity capillary zone electrophoresis (RPCE)method

    SciTech Connect

    Metcalf, S.G.

    1998-06-10

    This paper describes the first application of reverse polarity capillary zone electrophoresis (RPCE) for rapid and accurate determination of nitrate and nitrite in Hanford Defense Waste (HDW). The method development was carried out by using Synthetic Hanford Waste (SHW), followed by the analysis of 4 real HDW samples. Hexamethonium bromide (HMB) was used as electroosmotic flow modifier in borate buffer at pH 9.2 to decrease the electroosmotic flow (EOF) in order to enhance the speed of analysis and the resolution of nitrate and nitrite in high ionic strength HDW samples. The application of this capillary zone electrophoresis method, when compared with ion chromatography for two major components of HDW, nitrate and nitrite slightly reduced analysis time, eliminated most pre-analysis handling of the highly radioactive sample, and cut analysis wastes by more than 2 orders of magnitude. The analysis of real HDW samples that were validated by using sample spikes showed a concentration range of 1.03 to 1.42 M for both nitrate. The migration times of the real HDW and the spiked HDW samples were within a precision of less than 3% relative standard deviation. The selectivity ratio test used for peak confirmation of the spiked samples was within 96% of the real sample. Method reliability was tested by spiking the matrix with 72.4 mM nitrate and nitrite. Recoveries for these spiked samples were 93-103%.

  16. Expanding the Spectrum of Colonic Manifestations in Tuberous Sclerosis: L-Cell Neuroendocrine Tumor Arising in the Background of Rectal PEComa.

    PubMed

    Kolin, David L; Duan, Kai; Ngan, Bo; Gerstle, J Ted; Krzyzanowska, Monika K; Somers, Gino R; Mete, Ozgur

    2017-07-21

    Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous condition that predisposes to numerous proliferative lesions, including perivascular epithelioid cell tumors (PEComas), such as lymphangioleiomyomatosis (LAM) and angiomyolipomas, and rare neuroendocrine neoplasms. We describe herein a TSC2-harboring tuberous sclerosis patient manifesting with a synchronous well-differentiated L-cell rectal neuroendocrine tumor and leiomyomatosis-like LAM of the rectum. The background large bowel wall was thickened by confluent nodular areas comprising vessels and spindle-to-epithelioid cells, which are immunoreactive for myoid (smooth muscle actin, muscle specific actin, and desmin) and melanocytic markers (HMB45, Melan-A, microphthalmia transcription factor, and CD117). With the exception of TSC-related pancreatic neuroendocrine tumors, the association between tuberous sclerosis and neuroendocrine neoplasms remains largely unknown in the gastrointestinal tract. Neuroendocrine tumorigenesis in tuberous sclerosis is often linked to inactivating mutations of TSC2 leading to aberrant activation of mammalian target of rapamycin (mTOR) pathway. In this report, we document, for the first time, two foci of L-cell rectal neuroendocrine tumor arising in the setting of tuberous sclerosis, thus broadening the spectrum of TSC-associated endocrine disorders. Moreover, to our knowledge, this is only the second documented case of gastrointestinal leiomyomatosis-like LAM in a patient with tuberous sclerosis. The current case provides further evidence that, similar to pancreatic neuroendocrine tumors, neuroendocrine tumors of the luminal gastrointestinal tract may also be a feature of tuberous sclerosis and can be seen in association with PEComas.

  17. Angiogenesis and lymphangiogenesis in sporadic hepatic angiomyolipoma.

    PubMed

    Xian, Zhi-Hong; Cong, Wen-Ming; Lu, Xin-Yuan; Yu, Hua; Wu, Meng-Chao

    2011-07-15

    Angiogenesis and lymphangiogenesis are critical processes for tumor growth, invasion, and metastasis. The present study aimed to investigate the distribution and clinical significance of angiogenesis and lymphangiogenesis in hepatic angiomyolipoma (AML). We performed immunohistochemical staining for endothelial cell markers (CD34 and podoplanin) on 80 cases of sporadic hepatic AMLs. Microvessel density (MVD) and lymphatic vessel density (LVD) were determined in intratumoral and peritumoral regions and adjacent non-tumorous liver tissues. All hepatic AMLs showed positive staining for CD34 and podoplanin. Intratumoral and peritumoral MVDs and LVDs were significantly higher than those in adjacent liver tissues (P<0.001). No statistical difference in both MVD and LVD was found between intratumoral and peritumoral areas. Large tumors (>5cm) had a significantly increased MVD and LVD as compared with smaller tumors. A significant positive correlation was found between average LVDs and MVDs (r=0.567, P<0.001), and LVDs were a relatively lower event as compared with MVDs. Double immunostaining revealed that no neoplastic cells positive for HMB-45, an antibody reacting with melanosome-associated antigen, were concurrently immunoreactive for endothelial cell markers. In conclusion, intratumoral and peritumoral angiogenesis and lymphangiogenesis commonly occur in hepatic AMLs, thus representing potential therapeutic targets for this disease.

  18. Site-specific migration of human fetal melanocytes in volar skin.

    PubMed

    Nakamura, Motoki; Fukunaga-Kalabis, Mizuho; Yamaguchi, Yuji; Furuhashi, Takuya; Nishida, Emi; Kato, Hiroshi; Mizuno, Toshihiko; Sugiura, Mayumi; Morita, Akimichi

    2015-05-01

    Melanocytes originate from the neural crest and migrate ventrally from the dorsal neural tube during embryogenesis. How human melanocytes locate at their suitable positions during embryogenesis, however, is unclear. Although a growing body of evidence indicates that melanocytes, melanoblasts, and melanocyte stem cells are closely related to hair follicles, little is known about volar skin. The aim of this study was to observe skin development during human fetal period and clarify the site-specific migration process of human fetal sole melanocytes. We obtained 4-mm punch biopsies from the scalp, back, abdomen, and right sole of 36 aborted fetuses (gestational age 12-21 weeks). We compared the migration process between hairly areas and volar areas by immunohistochemical staining. Immunohistochemical examination revealed that gp100 (HMB-45) sensitively detects human melanocytes in embryogenesis. Melanocytes were present at the epidermal base, where hair placodes/buds form at 12-15 weeks gestation. Fetal melanocytes in hair follicles are supplied from the epidermis. In volar skin, melanocytes originally localize only in the acrosyringium, where they migrate deeper into with gland development at 16-18 weeks gestation. Palmoplantar melanocyte migration and maturation processes differ considerably from those of the other hairy skin sites. Eccrine sweat glands seem to have a central role in the palmoplantar melanocyte migration process, similar to the role of hair follicles in hairy sites. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Pilonidal sinus associated with cellular blue nevus. A previously unrecognized association.

    PubMed

    Val-Bernal, José Fernando; González-Vela, María Carmen; Hermana, Sandra; Garijo, María Francisca; González-López, Marcos A

    2007-12-01

    A neoplasm associated with a pilonidal sinus (PS) is a rare occurrence in the course of a common disease. Early detection is imperative. To our knowledge, pilonidal disease associated with a cellular blue nevus (CBN) has not been reported. There is a 10% diagnostic error rate with this last lesion. Here we report the case of a 19-year-old man with recurrent sacrococcygeal PS infection associated with an indurated dome-shaped blue-black nodule 1.7 cm in diameter. Clinical diagnosis of the nodule was uncertain suggesting a pigmentary or a vascular tumor. A complete resection of the two lesions was achieved. Pathological study showed a CBN showing a predominantly alveolar pattern associated with a chronic pilonidal disease. The tumor cells showed diffuse strong reactivity for melan-A and HMB-45, and focal reactivity for S-100 protein. Staining for Ki-67 (MIB1) was virtually negative. Differential diagnoses included atypical CBN, borderline melanocytic tumor and malignant melanoma. Radical excision provides a good prognosis for the rare association consisting of a common disease such as PS with the uncommon CBN.

  20. Pediatric Papillary Renal Cell Carcinoma in a Horseshoe Kidney: A Case Report with Review of the Literature

    PubMed Central

    Loya-Solis, Abelardo; Alemán-Meza, Lucía; Canales-Martínez, Luis Carlos; Franco-Márquez, Rodolfo; Rincón-Bahena, Alim Adriana; Nuñez-Barragán, Karla María; Garza-Guajardo, Raquel; Ponce-Camacho, Marco Antonio

    2015-01-01

    Renal cell carcinoma is the most common malignancy of the kidney in adults. In children, however, it only accounts for an estimated 1.8 to 6.3% of all pediatric malignant renal tumors. Papillary renal cell carcinoma is the second most common type of renal cell carcinoma in children. We present the case of a 12-year-old boy with a 2-month history of abdominal pain, unexplained weight loss, and gross hematuria. Computed tomography revealed a horseshoe kidney and a well-defined mass of 4 cm arising from the lower pole of the right kidney. Microscopically the tumor was composed of papillae covered with cells with abundant eosinophilic cytoplasm and high-grade nuclei with prominent nucleoli. Immunohistochemistry was performed; EMA, Vimentin, and AMACR were strongly positive while CK7, CD10, RCC antigen, TFE3, HMB-45, and WT-1 were negative. Currently, 10 months after the surgical procedure, the patient remains clinically and radiologically disease-free. PMID:26301110

  1. Point of care assessment of melanoma tumor signaling and metastatic burden from μNMR analysis of tumor fine needle aspirates and peripheral blood.

    PubMed

    Gee, Michael S; Ghazani, Arezou A; Haq, Rizwan; Wargo, Jennifer A; Sebas, Matthew; Sullivan, Ryan J; Lee, Hakho; Weissleder, Ralph

    2017-04-01

    This study evaluates μNMR technology for molecular profiling of tumor fine needle aspirates and peripheral blood of melanoma patients. In vitro assessment of melanocyte (MART-1, HMB45) and MAP kinase signaling (pERK, pS6K) molecule expression was performed in human cell lines, while clinical validation was performed in an IRB-approved study of melanoma patients undergoing biopsy and blood sampling. Tumor FNA and blood specimens were compared with BRAF genetic analysis and cross-sectional imaging. μNMR in vitro analysis showed increased expression of melanocyte markers in melanoma cells as well as increased expression of phosphorylated MAP kinase targets in BRAF-mutant melanoma cells. Melanoma patient FNA samples showed increased pERK and pS6K levels in BRAF mutant compared with BRAF WT melanomas, with μNMR blood circulating tumor cell level increased with higher metastatic burden visible on imaging. These results indicate that μNMR technology provides minimally invasive point-of-care evaluation of tumor signaling and metastatic burden in melanoma patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The histological diagnosis of metastases to the breast from extramammary malignancies

    PubMed Central

    Lee, Andrew H S

    2007-01-01

    This study aims to review histological and immunohistochemical features that are useful in the diagnosis of metastases to the breast. Histological features were compared between non‐haematological metastases to the breast and 100 consecutive core biopsy specimens of primary invasive carcinomas of the breast. 18 non‐haematological metastases to the breast were diagnosed over a 10‐year period (0.3% of malignant mammary tumours). Elastosis and carcinoma in situ were seen only in primary mammary cancers. Two‐thirds of tumours had features raising the possibility of metastasis, such as clear cell carcinoma suggestive of renal origin and small cell carcinoma suggestive of pulmonary origin. The features observed in haematological metastases are also described. Immunohistochemical panels to distinguish mammary carcinoma (oestrogen receptor, gross cystic fluid protein‐15) from common metastases to the breast, including carcinoma of the lung (thyroid transcription factor‐1), malignant melanoma (S100, HMB45, melan‐A) and ovarian serous papillary carcinoma (Wilms' tumour 1), are discussed. The pathologist has a key role in considering the diagnosis of metastasis to the breast if the histological features are unusual for a primary mammary tumour. The clinical history is vital in some cases. Immunohistochemistry plays a useful supplementary role. PMID:18042689

  3. Sinonasal Melanoma: A Case Report and Literature Review

    PubMed Central

    Alves, I. S. S.; Berriel, L. G. S.; Pinto, M. B.; Oliveira, C. F. P.; Cazzotto, A. C.; Moura, W. V.

    2017-01-01

    Purpose. Sinonasal malignant mucosal melanoma is a rare, aggressive tumour. Nasal obstruction and epistaxis are the most commonly reported symptoms, although symptomatology may develop late and be nonspecific, which tends to delay diagnosis, resulting in a poorer prognosis. Case Report. This report describes a 64-year-old male patient with nasal obstruction and epistaxis. Computed tomography of the facial sinuses revealed a large lesion in the right nasal cavity, with infiltration into the left cavity, ethmoidal cells, and erosion of the cribriform plate. Initial incisional biopsy revealed an undifferentiated carcinoma of the right maxillary sinus, staged as T4aN0M0. Induction chemotherapy was initiated with cisplatin and etoposide. Response to treatment was complete. The patient was then submitted to radiotherapy with concomitant cisplatin. Immunochemical analysis revealed positivity for vimentin, S100, and HMB-45 (human melanoma black 45), a result compatible with a diagnosis of malignant melanoma. Discussion. Due to the rarity of the tumour and the patient's complete response to chemotherapy and since no blackened lesion had been found at the previous exam, treatment was continued as planned. The patient remains healthy, with no metastasis or recurrence. He is currently being monitored by the clinical oncology team. PMID:28255482

  4. Pleomorphic leiomyosarcoma of the adrenal gland with osteoclast-like giant cells.

    PubMed

    Candanedo-González, Fernando A; Vela Chávez, Teresa; Cérbulo-Vázquez, Arturo

    2005-01-01

    Pleomorphic leiomyosarcoma (PLMS) of the adrenal gland is a rare tumor in an unusual location. A primary PLMS of the left adrenal gland is reported in a 59-yr-old Mexican woman who presented progressive flank pain and weight loss. The tumor measured 16 cm in diameter, showed markedly pleomorphic and osteoclast-like giant cells, necrosis, and high mitotic activity (average 15 per 10 high-power fields). The phenotype was supported by light microscopy and corroborated by immunohistochemistry. The neoplastic cells were strongly positive for muscle-specific actin, desmin, vimentin, and p53. They were negative for CD34, HMB45, estrogen receptors, and S-100 protein. The percentage of Ki-67 positive neoplastic cells was 7.6%. DNA content analysis by flow cytometry showed that tumor was diploid, with a high level of apoptosis. Extra-adrenal primary sites of origin were clinically excluded. The patient developed local recurrence and liver metastases 12 mo after initial treatment. She then received adjuvant chemotherapy and radiotherapy and the metastasis was resected. Twenty-four months later, she is alive with no evidence of disease. This is the second case of adrenal PLMS reported. This case exhibited a high histologic grade, aggressive behavior, and p53 overexpression, but diploid DNA content.

  5. Sentinel lymph node biopsy for conjunctival malignant melanoma: surgical techniques

    PubMed Central

    Wainstein, Alberto JA; Drummond-Lage, Ana P; Kansaon, Milhem JM; Bretas, Gustavo O; Almeida, Rodrigo F; Gloria, Ana LF; Figueiredo, Ana RP

    2015-01-01

    Background The purpose of this report is to examine the viability and safety of preoperative lymphoscintigraphy and radio guided sentinel lymph node (SLN) biopsy for conjunctival melanoma, and to identify the best technique to perform this procedure. Methods Three patients diagnosed with malignant melanoma of the conjunctiva underwent lymphoscintigraphy and SLN biopsy using a dual technique comprising isosulfan blue dye and technetium Tc 99m sulfur colloid. Each patient was anesthetized and the conjunctival melanoma was excised. SLNs were localized by a gamma probe, identified according to radioactivity and sentinel blue printing, and dissected, along with drainage of the associated lymphatic basins. The SLNs were evaluated by a pathologist using hematoxylin-eosin staining following serial sectioning and immunohistochemistry using a triple melanoma cocktail (S-100, Melan-A, and HMB-45 antigens). Results Two SLNs were stained in the jugular chain during preoperative lymphoscintigraphy in the first patient, two SLNs were identified in the preauricular and submandibular areas in the second patient, and two SLNs were identified in the submandibular and parotid areas in the third patient. All lymph nodes identified by lymphoscintigraphy were dissected and identified at surgery with 100% accuracy in all three patients. All SLNs were histologically and immunohistochemically negative. Patients had good cosmetic and functional results, and maintained their visual acuity and ocular motility. Conclusion Patients with conjunctival melanoma can undergo preoperative lymphoscintigraphy and SLN biopsy safely using radioactive technetium and isosulfan blue dye. PMID:25565762

  6. The role of bronchoscopy in the diagnosis of early lung cancer: a review.

    PubMed

    Andolfi, Marco; Potenza, Rossella; Capozzi, Rosanna; Liparulo, Valeria; Puma, Francesco; Yasufuku, Kazuhiro

    2016-11-01

    Lung cancer is the leading cause of cancer-related deaths worldwide with an overall 5-year survival rate of 17% after diagnoses. Indeed many patients tend to have a very poor prognosis, due to being diagnosed at an advanced stage. Conversely patients who are diagnosed at an early stage have a 5-year survival >70%, indicating that early detection of lung cancer is crucial to improve survival. Although flexible bronchoscopy is a relatively non-invasive procedure for patients suspected of having lung cancer, only 29% of carcinoma in situ (CIS) and 69% of microinvasive tumors were detectable using white light bronchoscopy (WLB) alone. As a result, in the past two decades, new bronchoscopic techniques have been developed to increase the yield and diagnostic accuracy, such as autofluorescence bronchoscopy (AFB), narrow band imaging (NBI) and high magnification bronchovideoscopy (HMB). However, due to the low specificity and the limitation to detect only proximal bronchial tree, new probe-based technologies have been introduced: radial endobronchial ultrasound (R-EBUS), optical coherence tomography (OCT), confocal laser endomicroscopy (CLE) and laser Raman spectroscopy (LRS). To date, although tissue biopsy remains the gold standard for diagnosing malignant/premalignant airway disease and some techniques are still investigational, bronchoscopic technologies can be considered the safest and most accurate tools to evaluate both central and distal airway mucosa.

  7. Hepatic perivascular epithelioid cell tumor

    PubMed Central

    Tang, Da; Wang, Jianmin; Tian, Yuepeng; Li, Qiuguo; Yan, Haixiong; Wang, Biao; Xiong, Li; Li, Qinglong

    2016-01-01

    Abstract Rational: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm which expresses both myogenic and melanocytic markers. PEComas are found in a variety locations in the body, but up to now only approximately 30 cases about hepatic perivascular epithelioid cell tumor are reported in English language worldwide. Patient concerns: A 32-year-old woman was admitted in our hospital with intermittent right upper quadrant pain for 1 month and recent (1 day) progressive deterioration. Diagnoses: Based on the results of the laboratory examinations and the findings of the computed tomography, the diagnosis of hepatic hamartoma or the hepatocecullar carcinoma with hemorrhage was made. Interventions: The patient underwent a segmentectomy of the liver, and the finally diagnosis of hepatic PEComa was made with immunohistochemical confirmation with HMB-45 and SMA. Outcomes: There is no clinical or radiographic evidence of recurrence 9 months after surgery. Lessons: This kind of tumor is extremely rare and the natural history of PEComa is uncertain, as the treatment protocol for hepatic PEComa has not reached a consensus. But the main treatment of the disease may be surgical resection. Only after long term follow-up can we know whether the tumor is benign or malignant. It appears that longer clinical follow-up is necessary in all patients with hepatic PEComas. PMID:28002331

  8. Clinical categories of exaggerated skin reactions to mosquito bites and their pathophysiology.

    PubMed

    Tatsuno, Kazuki; Fujiyama, Toshiharu; Matsuoka, Hiroyuki; Shimauchi, Takatoshi; Ito, Taisuke; Tokura, Yoshiki

    2016-06-01

    Mosquito bites are skin irritating reactions, which usually resolve spontaneously without intensive medical care. However, in certain situations, mosquito bites may form a more vicious reaction, sometimes accompanying fever and systemic symptoms. In such cases, the presence of rare hematological disorders, abnormalities in eosinophils and/or association with Epstein-Barr virus (EBV) may underlie. Importantly, hypersensitivity to mosquito bites (HMB), which is characterized by necrotic skin reactions to mosquito bites with various systemic symptoms, is often observed in association with EBV infection and natural killer (NK) cell lymphoproliferative disorder. Exaggerated skin reaction to mosquito bites is also seen in Wells' syndrome. While strong Th2-skewing immune dysregulation is apparent in the patients, they also show robust CD4(+) T cell proliferation in response to mosquito salivary gland extracts, indicating close association between Wells' syndrome and mosquito bites. Similar skin reaction to mosquito bites is also noticed in certain types of B cell neoplasm, although the role of B cells in this peculiar reaction to mosquito bites is yet to be elucidated. In this review, we will discuss the current knowledge of exaggerated reaction toward mosquito bites seen in conjunction with these unique hematological disorders, and examine the scientific studies and observations reported in previous literatures to organize our current understanding of the pathogenesis of this distinct disorder.

  9. γδ T-cell function is inhibited in end-stage renal disease and impacted by latent tuberculosis infection.

    PubMed

    Juno, Jennifer A; Waruk, Jillian L M; Harris, Angela; Mesa, Christine; Lopez, Carmen; Bueti, Joe; Ball, T Blake; Kiazyk, Sandra A

    2017-10-01

    Patients with end-stage renal disease (ESRD) are at elevated risk of acquiring infectious diseases, including tuberculosis (TB). Inflammation and uremia negatively impact immune function in this population, but specific pathways involved in TB immunity have not been identified. Although γδ T cells are known to contribute to protection from TB, their phenotype and function in patients with ESRD is relatively unknown. To determine this we recruited 20 patients with and 20 without ESRD (controls), with or without latent TB infection to assess γδ T cell frequency, surface phenotype, and cytokine production by flow cytometry in response to stimulation. γδ T cells derived from patients with ESRD exhibited significantly lower expression of CCR5, CXCR3, and CD26 compared to controls. Furthermore, patients with ESRD, particularly the group with latent TB infection, exhibited poor IFNγ, TNFα, and GMCSF responses to stimulation with either phosphoantigen HMB-PP, IL-12/IL-18, E. coli, or phorbol myristate acetate and ionomycin. Similar dysfunctional responses were observed in patients with active TB. Surprisingly, neither the γδ phenotype nor its function was associated with plasma markers of inflammation or microbial translocation. Thus, there is significant perturbation of the γδ T-cell population in patients with ESRD, particularly in those with latent TB infection. Copyright © 2017 International Society of Nephrology. All rights reserved.

  10. Como Lo Hago Yo: Myelomeningocele

    PubMed Central

    Lazareff, Jorge

    2014-01-01

    Fortificación con ádico fólico es efectiva, pero aún falta conciencia en los jóvenes. La legalidad del aborto aumenta la importancia de la consulta prenatal. Realizo la cirugía bajo microcoscopio por razones didácticas. Irrigación continua para reducir la temperatura del tejido. Trato a la plaqueta como tejido viable. No suturo la plaqueta. No cierro músculo. ATB por una semana después de cirugía. Hidrocefalia: Válvula en todos los casos de ventriculomegalia. Médula anclada: Desanclar una sola vez. Chiari II: Revisar la válvula. Incluir en el seguimiento rendimiento escolar, puede indicar obstrucción de la válvula o médula anclada. PMID:24791217

  11. [TOBACCO CONSUMPTION AMONG ADULTS IN MONTERREY: RELATION TO EXERCISE REGULARLY AND FAMILY].

    PubMed

    Ruiz-Juan, Francisco; Isorna-Folgar, Manuel; Ruiz-Risueño, Jorge; Vaquero-Cristóbal, Raquel

    2015-08-01

    Objetivo: determinar la relación entre práctica físico- deportiva y consumo de tabaco en adultos mexicanos en función de una serie de variables sociodemográficas y la influencia de la familia sobre estos hábitos. Métodos: 978 adultos mexicanos (483 varones y 495 mujeres) fueron entrevistados mediante cuestionario por rutas aleatorias. Se utilizó una regresión logística multinomial para calcular odds ratio (OR) e intervalo de confianza (IC = 95%). Resultados: ser hombre es un factor de riesgo en cuanto a la frecuencia y cantidad de tabaco consumido. La franja de edad en la que aumenta la probabilidad de consumir tabaco es la de 18 a 45 años, siendo el riesgo de fumar menor a medida que la edad aumenta. El riesgo de consumir tabaco se ve significativamente disminuido entre aquellos que no tienen estudios. Los que nunca han realizado ejercicio físico tienen una menor probabilidad de fumar, siendo los que la han abandonado los que con más frecuencia fuman. El contexto familiar constituye un factor de riesgo manifiesto en relación con la frecuencia de consumo de tabaco. Con respecto a la relación con el consumo de alcohol, se ha detectado que los consumidores de alcohol tienen más probabilidad de ser fumadores. Conclusiones: el consumo de tabaco en altas frecuencias y cantidades y la práctica de actividad física son conductas que están inversamente relacionadas. También se ha detectado una relación directamente proporcional entre la frecuencia y la cantidad de consumo de tabaco y alcohol, así como una gran influencia de la familia en el hábito de fumar.

  12. Bipyrimidine ruthenium(II) arene complexes: structure, reactivity and cytotoxicity.

    PubMed

    Betanzos-Lara, Soledad; Novakova, Olga; Deeth, Robert J; Pizarro, Ana M; Clarkson, Guy J; Liskova, Barbora; Brabec, Viktor; Sadler, Peter J; Habtemariam, Abraha

    2012-10-01

    The synthesis and characterization of complexes [(η(6)-arene)Ru(N,N')X][PF(6)], where arene is para-cymene (p-cym), biphenyl (bip), ethyl benzoate (etb), hexamethylbenzene (hmb), indane (ind) or 1,2,3,4-tetrahydronaphthalene (thn), N,N' is 2,2'-bipyrimidine (bpm) and X is Cl, Br or I, are reported, including the X-ray crystal structures of [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)I][PF(6)] and [(η(6)-etb)Ru(bpm)Cl][PF(6)]. Complexes in which N,N' is 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione or 4,7-diphenyl-1,10-phenanthroline (bathophen) were studied for comparison. The Ru(II) arene complexes undergo ligand-exchange reactions in aqueous solution at 310 K; their half-lives for hydrolysis range from 14 to 715 min. Density functional theory calculations on [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-p-cym)Ru(bpm)Br][PF(6)], [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)Br][PF(6)] and [(η(6)-bip)Ru(bpm)I][PF(6)] suggest that aquation occurs via an associative pathway and that the reaction is thermodynamically favourable when the leaving ligand is I > Br ≈ Cl. pK (a)* values for the aqua adducts of the complexes range from 6.9 to 7.32. A binding preference for 9-ethylguanine (9-EtG) compared with 9-ethyladenine (9-EtA) was observed for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-hmb)Ru(bpm)Cl](+), [(η(6)-ind)Ru(bpm)Cl](+), [(η(6)-thn)Ru(bpm)Cl](+), [(η(6)-p-cym)Ru(phen)Cl](+) and [(η(6)-p-cym)Ru(bathophen)Cl](+) in aqueous solution at 310 K. The X-ray crystal structure of the guanine complex [(η(6)-p-cym)Ru(bpm)(9-EtG-N7)][PF(6)](2) shows multiple hydrogen bonding. Density functional theory calculations show that the 9-EtG adducts of all complexes are thermodynamically preferred compared with those of 9-EtA. However, the bmp complexes are inactive towards A2780 human ovarian cancer cells. Calf thymus DNA interactions for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)] and [(η(6)-p

  13. The addition of beta-hydroxy-beta-methylbutyrate and isomaltulose to whey protein improves recovery from highly demanding resistance exercise.

    PubMed

    Kraemer, William J; Hooper, David R; Szivak, Tunde K; Kupchak, Brian R; Dunn-Lewis, Courtenay; Comstock, Brett A; Flanagan, Shawn D; Looney, David P; Sterczala, Adam J; DuPont, William H; Pryor, J Luke; Luk, Hiu-Ying; Maladoungdock, Jesse; McDermott, Danielle; Volek, Jeff S; Maresh, Carl M

    2015-01-01

    This study evaluated whether a combination of whey protein (WP), calcium beta-hydroxy-beta-methylbutyrate (HMB), and carbohydrate exert additive effects on recovery from highly demanding resistance exercise. Thirteen resistance-trained men (age: 22.6 ± 3.9 years; height: 175.3 ± 12.2 cm; weight: 86.2 ± 9.8 kg) completed a double-blinded, counterbalanced, within-group study. Subjects ingested EAS Recovery Protein (RP; EAS Sports Nutrition/Abbott Laboratories, Columbus, OH) or WP twice daily for 2 weeks prior to, during, and for 2 days following 3 consecutive days of intense resistance exercise. The workout sequence included heavy resistance exercise (day 1) and metabolic resistance exercise (days 2 and 3). The subjects performed no physical activity during day 4 (+24 hours) and day 5 (+48 hours), where recovery testing was performed. Before, during, and following the 3 workouts, treatment outcomes were evaluated using blood-based muscle damage markers and hormones, perceptual measures of muscle soreness, and countermovement jump performance. Creatine kinase was lower for the RP treatment on day 2 (RP: 166.9 ± 56.4 vs WP: 307.1 ± 125.2 IU · L(-1), p ≤ 0.05), day 4 (RP: 232.5 ± 67.4 vs WP: 432.6 ± 223.3 IU · L(-1), p ≤ 0.05), and day 5 (RP: 176.1 ± 38.7 vs 264.5 ± 120.9 IU · L(-1), p ≤ 0.05). Interleukin-6 was lower for the RP treatment on day 4 (RP: 1.2 ± 0.2 vs WP: 1.6 ± 0.6 pg · ml(-1), p ≤ 0.05) and day 5 (RP: 1.1 ± 0.2 vs WP: 1.6 ± 0.4 pg · ml(-1), p ≤ 0.05). Muscle soreness was lower for RP treatment on day 4 (RP: 2.0 ± 0.7 vs WP: 2.8 ± 1.1 cm, p ≤ 0.05). Vertical jump power was higher for the RP treatment on day 4 (RP: 5983.2 ± 624 vs WP 5303.9 ± 641.7 W, p ≤ 0.05) and day 5 (RP: 5792.5 ± 595.4 vs WP: 5200.4 ± 501 W, p ≤ 0.05). Our findings suggest that during times of intense conditioning, the recovery benefits of WP are enhanced with the addition of HMB and a slow-release carbohydrate. We

  14. Bleeding pattern and user satisfaction in second consecutive levonorgestrel-releasing intrauterine system users: results of a prospective 5-year study

    PubMed Central

    Heikinheimo, O.; Inki, P.; Schmelter, T.; Gemzell-Danielsson, K.

    2014-01-01

    STUDY QUESTION What is the bleeding pattern during second consecutive levonorgestrel-releasing intrauterine system (LNG-IUS) use? SUMMARY ANSWER Consecutive use of LNG-IUS is associated with a predictable bleeding pattern, characterized by the absence of the initial period of irregular bleeding seen after interval insertion of an LNG-IUS and a non-bleeding pattern in the vast majority of women. WHAT IS KNOWN ALREADY With increased popularity of the LNG-IUS for long-term birth control and treatment of heavy menstrual bleeding (HMB), consecutive use of the system is becoming more frequent. One previous study showed 60% amenorrhea rate in consecutive IUS users; however, the sample size was small. STUDY DESIGN, SIZE, DURATION A prospective multicenter study in four European countries recruited women who wished to continue with LNG-IUS use immediately after the first 5-year period. A total of 204 women were followed up until the end of the first year of the second IUS. Thereafter 170 women continued into the extension phase of the study up to the full 5 years of use of the second IUS and 144 women continued to the end of the study. PARTICIPANTS, SETTING, METHODS A total of 170 women (mean age 39 years) who had been using their first LNG-IUS for between 4 years 3 months and 4 years 9 months, either for contraception or for treatment of HMB, and who planned to replace the device with a new LNG-IUS, were recruited and followed up to 5 years of the second IUS use. A total of 17 centers in four European countries were involved in the study. Bleeding patterns were analyzed using daily bleeding diaries using 90-day reference periods (RP) for the first year of the second IUS use and for the last RP of each year during Years 2–5 of use. MAIN RESULTS AND THE ROLE OF CHANCE Approximately 70% of women were free of bleeding during Years 2–5 and up to 49% were amenorrheic. There was a slight increase in the number of bleeding/spotting days of ∼3 days during the first RP

  15. Setaria cervi dual specific phosphatase: characterization and its effect on eosinophil degranulation.

    PubMed

    Rathaur, S; Rai, R; Srikanth, E; Srivastava, S

    2009-07-01

    Setaria cervi, a bovine filarial parasite contains significant acid phosphatase (AcP) activity in its various life stages. Two forms of AcP were separated from somatic extract of adult female parasite using cation exchange, gel filtration and concavalin affinity chromatography. One form having a molecular mass of 79 kDa was characterized as dual specific protein tyrosine phosphatase (ScDSP) based on substrate specificity and inhibition studies. With various substrates tested, it showed significant activity in the order of phospho-L-tyrosine>pNPP>ADP>phospho-L-serine. Inhibition by orthovanadate, fluoride, molybdate, and zinc ions further confirms protein tyrosine phosphatase nature of the enzyme. Km and Vmax determined with various substrates were found to be 16.66 mM, 25.0 microM/ml/min with pNPP; 20.0 mM, 40.0 microM/ml/min with phospho-L-tyrosine and 27.0 mM, 25.0 microM/ml/min with phospho-L-serine. KI with pNPP and sodium orthovanadate (IC50 33.0 microM) was calculated to be 50.0 mM. Inhibition with pHMB, silver nitrate, DEPC and EDAC suggested the presence of cysteine, histidine and carboxylate residues at its active site. Cross-reactivity with W. bancrofti-infected sera was demonstrated by Western blotting. ScDSP showed elevated levels of IgE in chronic filarial sera using ELISA. Under in vitro conditions, ScDSP resulted in increased effector function of human eosinophils when stimulated by IgG, which showed a further decrease with increasing enzyme concentration. Results presented here suggest that S. cervi DSP should be further studied to determine its role in pathogenesis and the persistence of filarial parasite.

  16. A new device for magnetic stirring-assisted dispersive liquid-liquid microextraction of UV filters in environmental water samples.

    PubMed

    Zhang, Ping-Ping; Shi, Zhi-Guo; Yu, Qiong-Wei; Feng, Yu-Qi

    2011-02-15

    A new method based on dispersive liquid-liquid microextraction (DLLME) in combination with high-performance liquid chromatography (HPLC) has been developed for the analysis of UV filters. A specially designed flask, which has two narrow open necks with one of them having a capillary tip, was employed to facilitate the DLLME process. By adopting such a device, the extraction and subsequent phase separation were conveniently achieved. A binary solvent system of water sample and low-density extraction solvent (1-octanol) was used for the DLLME and no disperser solvent was involved. The extraction was accelerated by magnetic agitation of the two phases. After extraction, phase separation of the extraction solvent from the aqueous sample was easily achieved by leaving the extraction system statically for a while. No centrifugation step involving in classical DLLME was necessary. The analyte-enriched phase, floating above the sample solution, was elevated and concentrated into the narrow open tip of the flask by adding pure water into it via the other port, which was withdrawn with a microsyringe for the subsequent HPLC analysis. Under the optimized conditions, the limits of detection for the analytes were in range of 0.2-0.8ngmL(-1) .The linearity ranges were 8-20,000 ng mL(-1) for HB, 7-20,000 ng mL(-1) for DB, 8-10,000 ng mL(-1) for BP and 5-20,000 ng mL(-1) for HMB, respectively. Enrichment factors ranging from 59 to 107 folders were obtained for the analytes. The relative standard deviations (n=3) at a spiked level of 80 ng mL(-1) were between 1.4 and 4.8%. The proposed magnetic stirring-assisted DLLME method was successfully applied to the analysis of lake water samples.

  17. Malignant melanoma in the penguin: characterization of the clinical, histologic, and immunohistochemical features of malignant melanoma in 10 individuals from three species of penguin.

    PubMed

    Duncan, Ann E; Smedley, Rebecca; Anthony, Simon; Garner, Michael M

    2014-09-01

    Malignant melanomas are aggressive neoplasms that are relatively common in penguins compared to other avian species. In this study, the clinical and pathologic characteristics of melanocytic neoplasms in five macaroni (Eudyptes chrysolophus), three rock hopper (Eudyptes chrysocome), and two Humboldt (Spheniscus humboldti) penguins are described. Tumors most commonly occurred in the skin of the foot or hock, and were seen in the subcutaneous muscle, especially near the beak/oral cavity. Gross lesions were usually heavily pigmented, becoming raised and ulcerated over time. Humboldt penguins had a unique presentation, forming variably pigmented, cornified lesions in the inguinal area. Original case materials were obtained from all but two cases, and were assessed to define the characteristics of malignancy, evaluate four immunohistochemical markers for melanoma, and look for factors useful to informing prognosis and clinical decisions. Diagnosis was made histologically, based on morphologic features and pigmentation. Though not necessary for diagnosis, PNL-2 was found to be a useful immunohistochemical marker. HMB-45 showed unreliable positive labelling and S-100, Melan-A and Ki67 were not useful. Several factors were associated with prognosis, including gross surface dimension, mitotic index, depth of neoplastic cell invasion, and degree of surface ulceration. Metastatic spread occurred to the liver, lung, adrenal gland, brain, and bone; all lesions showed positive labelling to PNL-2. The average survival after diagnosis was 7 mo, though complete surgical excision of tumors less than 2.0 cm was curative in two cases and radiation therapy prolonged survival in one penguin. The underlying pathogenesis associated with the high prevalence of melanocytic neoplasms in captive penguins could not be identified. Three different molecular methods were performed to look for viral particles and results were negative. Advanced age is the most probable associated risk factor

  18. Primary histiocytic sarcoma of the brain mimicking cerebral abscess.

    PubMed

    Almefty, Rami O; Tyree, Tammy L; Fusco, David J; Coons, Stephen W; Nakaji, Peter

    2013-09-01

    Histiocytic sarcoma is a rare malignancy with only 10 reports confirmed primarily involving the CNS. The diagnosis is dependent on the finding of malignant cells with histiocytic morphology and immunophenotype. The authors report a case of pathologically proven HS of the CNS. A 16-year-old boy presented with headaches, emesis, and altered sensorium. Noncontrast head CT scanning demonstrated a left parietal mass consistent with a tumor. Surgery was undertaken. Intraoperative findings revealed green-yellow exudates consistent with an abscess. Cultures were obtained and broad-spectrum antibiotics were started. The patient subsequently underwent multiple surgical procedures, including drainage and debulking of abscesses and hemicraniectomy. Two months after initial presentation, the patient's diagnosis of histiocytic sarcoma was confirmed. Pathological examination demonstrated necrotizing inflammation with preponderant neutrophil infiltration, variably atypical mononuclear and multinucleate histiocytes, and numerous mitoses. Additional immunohistochemistry studies confirmed immunoreactivity for CD68, CD45, CD45RO, and CD15 and were negative for CD3, CD20, melanoma cocktail, CD30, CD1a, CD34, HMB-45, and melan-A. Once the diagnosis of histiocytic sarcoma was confirmed, antibiotics were stopped and radiation therapy was undertaken. Despite treatment, the patient's neurological status continued to decline and the patient died 126 days after initial presentation. This case represents a rare confirmed example of CNS histiocytic sarcoma. A profound inflammatory infiltrate seen on pathology and green exudates seen intraoperatively make the condition difficult to distinguish from an abscess. Immunohistochemistry showing a histiocytic origin and negative for myeloid, dendritic, or other lymphoid markers is essential for the diagnosis. Further research is needed to establish consensus on treatment.

  19. MiT family translocation renal cell carcinoma.

    PubMed

    Argani, Pedram

    2015-03-01

    The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Melanotic MiT family translocation neoplasms: Expanding the clinical and molecular spectrum of this unique entity of tumors.

    PubMed

    Saleeb, Rola M; Srigley, John R; Sweet, Joan; Doucet, Cedric; Royal, Virginie; Chen, Ying-Bei; Brimo, Fadi; Evans, Andrew

    2017-08-25

    MiT family translocation tumors are a group of neoplasms characterized by translocations involving MiT family transcription factors. The translocation renal cell carcinomas, TFE3 (Xp11.2) and TFEB (t6;11) are known members of this family. Melanotic Xp11 translocation renal cancer is a more recently described entity. To date only 14 cases have been described. It is characterized by a distinct set of features including a nested epithelioid morphology, melanin pigmentation, labeling for markers of melanocytic differentiation, lack of labeling for markers of renal tubular differentiation, predominance in a younger age population and association with aggressive clinical behavior. There are noted similarities between that entity and TFE3 associated PEComas. There are no cases reported of equivalent melanotic TFEB translocation renal cancer. We report 2 rare cases of melanotic translocation renal neoplasms. The first is a melanotic TFE3 translocation renal cancer with an indolent clinical course, occurring in a patient more than 3-decades older than the usual average age in which such tumors have been described. The other case is, to our knowledge, the first reported melanotic TFEB translocation cancer of the kidney. Both cases exhibit the same H&E morphology as previously reported in melanotic translocation renal cancers and label accordingly with HMB45 and Melan-A. While the TFE3 melanotic tumor lacked any evidence of renal tubular differentiation, the TFEB melanotic cancer exhibited some staining for renal tubular markers. Based on the unique features noted above, these two cases expand the clinical and molecular spectrum of the melanotic translocation renal cancers. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Validation of putative reference genes for gene expression studies in heat stressed and α-MSH treated melanocyte cells of Bos indicus using real-time quantitative PCR.

    PubMed

    Choudhary, Renuka; Kumar, Sudarshan; Singh, Sohan V; Sharma, Anil K; Goud, Talla Sridhar; Srivastava, Amrendra K; Kumar, Anil; Mohanty, Ashok K; Upadhyay, Ramesh C

    2016-06-01

    Normalization of cellular mRNA data using internal reference gene (IRG) is an essential step in expression analysis studies. MIQE guidelines ensure that the choice and appropriateness of IRG should be validated for particular tissues or cell types and specific experimental designs. The objective of the present study was to assess 15 IRGs from different functional classes that could serve as best IRGs for Bos indicus (Tharparkar cattle) melanocyte cells under heat stress and hormonal treatment. We implemented the use of geNorm, NormFinder and BestKeeper algorithm to measure the stability of the gene transcript. A total of 15 IRGs (ACTB, BZM, EEF1, GAPDH, GTP, HMBS, HPRT, RPL22, RPL4, RPS15, RPS18, RPS23, RPS9, UBC and UXT) from different functional classes were evaluated. Pair wise comparisons using geNorm revealed that HPRT and RPS23 were the most stable combination of IRGs with M-value of 0.29 followed by UXT (0.30) and RPL4 (0.31). The NormFinder analysis also identified the same set of stably expressed genes (UXT, RPL4, RPS23 and HPRT); however, the rank order was little different. The UXT gene showed lowest crossing point SD and CV values of 0.30 and 1.17, respectively indicating its maximum expression stability through BestKeeper analysis. The present study indicated that, ACTB and HMB were not reliable IRGs for melanocytes cells on account of their lower expression stability. Current study further revealed that UXT, HPRT and RPS23 are the best IRGs for normalization of qPCR data in Bos indicus melanocyte cells under heat stress and hormonal treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Transcriptional profiling of Actinobacillus pleuropneumoniae under iron-restricted conditions

    PubMed Central

    Deslandes, Vincent; Nash, John HE; Harel, Josée; Coulton, James W; Jacques, Mario

    2007-01-01

    Background To better understand effects of iron restriction on Actinobacillus pleuropneumoniae and to identify new potential vaccine targets, we conducted transcript profiling studies using a DNA microarray containing all 2025 ORFs of the genome of A. pleuropneumoniae serotype 5b strain L20. This is the first study involving the use of microarray technology to monitor the transcriptome of A. pleuropneumoniae grown under iron restriction. Results Upon comparing growth of this pathogen in iron-sufficient versus iron-depleted medium, 210 genes were identified as being differentially expressed. Some genes (92) were identified as being up-regulated; many have confirmed or putative roles in iron acquisition, such as the genes coding for two TonB energy-transducing proteins and the hemoglobin receptor HgbA. Transcript profiling also led to identification of some new iron acquisition systems of A. pleuropneumoniae. Genes coding for a possible Yfe system (yfeABCD), implicated in the acquisition of chelated iron, were detected, as well as genes coding for a putative enterobactin-type siderophore receptor system. ORFs for homologs of the HmbR system of Neisseria meningitidis involved in iron acquisition from hemoglobin were significantly up-regulated. Down-regulated genes included many that encode proteins containing Fe-S clusters or that use heme as a cofactor. Supplementation of the culture medium with exogenous iron re-established the expression level of these genes. Conclusion We have used transcriptional profiling to generate a list of genes showing differential expression during iron restriction. This strategy enabled us to gain a better understanding of the metabolic changes occurring in response to this stress. Many new potential iron acquisition systems were identified, and further studies will have to be conducted to establish their role during iron restriction. PMID:17355629

  3. Impact of human papillomavirus coinfections on the risk of high-grade squamous intraepithelial lesion and cervical cancer.

    PubMed

    Carrillo-García, Adela; Ponce-de-León-Rosales, Sergio; Cantú-de-León, David; Fragoso-Ontiveros, Verónica; Martínez-Ramírez, Imelda; Orozco-Colín, Asunción; Mohar, Alejandro; Lizano, Marcela

    2014-09-01

    The molecular and epidemiologic effect of human papillomavirus (HPV) coinfections in the risk of developing cervical cancer is yet unclear. The aim of this study was to determine the frequency HPV coinfections at different stages of cervical lesions in the development of cervical cancer and the impact of HPV specific type interactions on high-grade squamous intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) risk. HPV testing was performed in 931 cervical samples diagnosed as: negative for intraepithelial lesion or malignancy (NILM); low-grade squamous intraepithelial lesion (LSIL); HSIL; and ICC. For HPV detection and typing two sets of primers from the L1 region were used in the polymerase chain reaction method (PCR) (MY09/MY11/HMB01 and L1C1/L1C2.1/L1C2.2) and HPV type was determined by PCR product sequence. To look for multiple HPV infections, the E6 nested multiplex PCR method was performed in all DNA samples. Odds ratios were calculated as indexes of the strength of the association between the sample category (LSIL/NILM or ICC/HSIL) and the presence of a given viral combination. In HPV positive samples, coinfections are as common in ICC/HSIL as in LSIL/NILM (47.12% and 40.17%, respectively). There is an increased risk to ICC/HSIL when multiple high-risk HPV types are present. The coinfection of HPV68 with HPV16 increases the risk of ICC/HSIL (OR=14.54, P=0.012, after multivariate adjustment), related to the presence of HPV16 or HPV68 alone. These results sustain that specific HPV coinfections confer an increased risk to develop ICC/HSIL. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Purification and properties of three NAD(P)+ isozymes of L-glutamate dehydrogenase of Chlamydomonas reinhardtii.

    PubMed

    Moyano, E; Cárdenas, J; Muñoz-Blanco, J

    1992-02-13

    Three isozymes of glutamate dehydrogenase (GDH) of Chlamydomonas reinhardtii, induced under different trophic and stress conditions, have been purified about 800-1000-fold to electrophoretic homogeneity. They are hexamers of Mr 266,000-269,000 as deduced from gel filtration and sedimentation coefficient data. GDH1 consisted of six identical subunits of 44 kDa each, whereas both GDH2 and GDH3 consisted of six similar-sized monomers (4 of 44 kDa and 2 of 46 kDa). Optimum pH for the three activities with each pyridine nucleotide was identical (8.5 with NADH; 7.7 with NADPH; and 9.0 with NAD+). The isozymes exhibited similar high optimum temperature values (60-62 degrees C) and isoelectric points (7.9-8.1). Activity was enhanced in vitro by Ca2+ ions and strongly inhibited by pyridoxal 5'-phosphate, KCN, o-phenanthroline and EDTA, and to a lesser extent by pHMB and methylacetimidate. In the aminating reaction the three isozymes were inhibited in a concentration-dependent process by both NADH and NADPH, with apparent Km values for NH4+ ranging from 13-53 mM; 0.36-1.85 mM for 2-oxoglutarate and 0.07-0.78 mM for NADH and NADPH. In the deaminating reaction apparent Km values ranged from 0.64-3.52 mM for L-glutamate and 0.20-0.32 for NAD+. In addition, the three isozymes exhibited a non-hyperbolic kinetics for NAD+ with negative cooperativity (n = 0.8).

  5. Safety, Correlative Markers, and Clinical Results of Adjuvant Nivolumab in Combination with Vaccine in Resected High-Risk Metastatic Melanoma

    PubMed Central

    Gibney, Geoffrey T.; Kudchadkar, Ragini R.; DeConti, Ronald C.; Thebeau, Melissa S.; Czupryn, Maria P.; Tetteh, Leticia; Eysmans, Cabell; Richards, Allison; Schell, Michael J.; Fisher, Kate J.; Horak, Christine E.; Inzunza, H. David; Yu, Bin; Martinez, Alberto J.; Younos, Ibrahim; Weber, Jeffrey S.

    2015-01-01

    Purpose The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients. Experimental Design HLA-A*0201 positive patients with HMB-45, NY-ESO-1, and/or MART-1 positive resected tumors received nivolumab (1 mg/kg, 3 mg/kg, or 10 mg/kg i.v.) with a multi-peptide vaccine (gp100, MART-1, and NY-ESO-1 with Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 12 weeks for 8 doses. Primary objective was safety and determination of a maximum tolerated dose (MTD). Secondary objectives included relapse-free survival (RFS), overall survival (OS), and immunologic correlative studies. Results Thirty-three patients were enrolled. Median age was 47 years; 55% were male. Two patients had stage IIIC disease; 31 patients had stage IV disease. Median follow-up was 32.1 months. MTD was not reached. Most common related adverse events (>40%) were vaccine injection site reaction, fatigue, rash, pruritus, nausea, and arthralgias. Five related grade 3 adverse events [hypokalemia (1), rash (1), enteritis (1), and colitis (2)] were observed. Ten of 33 patients relapsed. Estimated median RFS was 47.1 months; median OS was not reached. Increases in CTLA-4+/CD4+, CD25+Treg/CD4+, and tetramer specific CD8+ T-cell populations were observed with treatment (P < 0.05). Trends for lower baseline myeloid-derived suppressor cell and CD25+Treg/CD4+ populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with RFS. Conclusions Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. PMID:25524312

  6. Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma.

    PubMed

    Gibney, Geoffrey T; Kudchadkar, Ragini R; DeConti, Ronald C; Thebeau, Melissa S; Czupryn, Maria P; Tetteh, Leticia; Eysmans, Cabell; Richards, Allison; Schell, Michael J; Fisher, Kate J; Horak, Christine E; Inzunza, H David; Yu, Bin; Martinez, Alberto J; Younos, Ibrahim; Weber, Jeffrey S

    2015-02-15

    The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients. HLA-A*0201 positive patients with HMB-45, NY-ESO-1, and/or MART-1 positive resected tumors received nivolumab (1 mg/kg, 3 mg/kg, or 10 mg/kg i.v.) with a multi-peptide vaccine (gp100, MART-1, and NY-ESO-1 with Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 12 weeks for 8 doses. Primary objective was safety and determination of a maximum tolerated dose (MTD). Secondary objectives included relapse-free survival (RFS), overall survival (OS), and immunologic correlative studies. Thirty-three patients were enrolled. Median age was 47 years; 55% were male. Two patients had stage IIIC disease; 31 patients had stage IV disease. Median follow-up was 32.1 months. MTD was not reached. Most common related adverse events (>40%) were vaccine injection site reaction, fatigue, rash, pruritus, nausea, and arthralgias. Five related grade 3 adverse events [hypokalemia (1), rash (1), enteritis (1), and colitis (2)] were observed. Ten of 33 patients relapsed. Estimated median RFS was 47.1 months; median OS was not reached. Increases in CTLA-4(+)/CD4(+), CD25(+)Treg/CD4(+), and tetramer specific CD8(+) T-cell populations were observed with treatment (P < 0.05). Trends for lower baseline myeloid-derived suppressor cell and CD25(+)Treg/CD4(+) populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with RFS. Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. ©2014 American Association for Cancer Research.

  7. Synthesis, crystal growth, structural and physicochemical studies of novel binary organic complex: 4-chloroaniline-3-hydroxy-4-methoxybenzaldehyde

    SciTech Connect

    Sharma, K.P.; Reddi, R.S.B.; Bhattacharya, S.; Rai, R.N.

    2012-06-15

    The solid-state reaction, which is solvent free and green synthesis, has been adopted to explore the novel compound. The phase diagram of 4-chloroaniline (CA) and 3-hydroxy-4-methoxybenzaldehyde (HMB) system shows the formation of a novel 1:1 molecular complex, and two eutectics on either sides of complex. Thermochemical studies of complex and eutectics have been carried out for various properties such as heat of fusion, entropy of fusion, Jackson's parameters, interfacial energy and excess thermodynamic functions. The formation of molecular complex was also studied by IR, NMR, elemental analysis and UV-Vis absorption spectra. The single crystal of molecular complex was grown and its XRD study confirms the formation of complex and identifies the crystal structure and atomic packing of crystal of complex. Transmission spectra of grown crystal of the complex show 70% transmittance efficiency with cut off wavelength 412 nm. The band gap and refractive index of the crystal of complex have also been studied. - Graphical abstarct: Exploiting phase diagram study and solvent free synthesis a novel compound was synthesized and its single crystal growth, atomic packing, energy band gap and refractive index were studied. Highlights: Black-Right-Pointing-Pointer Novel organic complex was synthesized using Green or solvent free synthesis. Black-Right-Pointing-Pointer Phase diagram study provided the information to identify the worthy composition of novel complex. Black-Right-Pointing-Pointer The single crystal of the sufficient size was grown from the ethanol solution. Black-Right-Pointing-Pointer Crystal analysis suggested that the covalent bond is formed between the two parent compounds. Black-Right-Pointing-Pointer The transmittance of the crystal was found to be 70% and it was transparent from 412 to 850 nm.

  8. Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis.

    PubMed

    Lambros, Maria Polikandritou; Parsa, Cyrus; Mulamalla, HariChandana; Orlando, Robert; Lau, Bernard; Huang, Ying; Pon, Doreen; Chow, Moses

    2011-02-04

    Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this is an important first step towards the development 3-D tissue as a screening tool.

  9. Pigmented Pheochromocytoma: an Unusual Variant of a Common Tumor.

    PubMed

    Kakkar, Aanchal; Kaur, Kavneet; Kumar, Tarun; Cherian, Libin Babu; Kaushal, Rohit; Sharma, Mehar Chand; Dhar, Anita; Seth, Amlesh; Jain, Deepali

    2016-03-01

    Pheochromocytoma is a neuroendocrine tumor arising from the adrenal medulla. A number of variants of pheochromocytoma are known; however, pigmented pheochromocytoma is extremely rare, with only few cases reported in literature. We report the cases of two patients with pigmented pheochromocytoma. Case 1 was a 28-year-old female who presented with complaints of breathlessness, palpitations, and anxiety for 5 years, which had worsened over the last 8 months. Computed tomography (CT) abdomen showed a right suprarenal mass. Case 2 was that of an 18-year-old girl who presented with similar complaints and was diagnosed with hypertension. CT abdomen showed bilateral adrenal masses. Urinary vanillyl mandelic acid was raised in both patients. Sections examined from all three tumors showed cells arranged in Zellballen pattern, separated by thin fibrovascular septae. Tumor cells showed moderate to marked nuclear pleomorphism in case 1. Mitoses were, however, not seen. There was no evidence of capsular or vascular invasion. Many of the tumor cells showed intracytoplasmic black pigment, which was positive for Fontana-Masson and was bleach-labile, confirming it as melanin. Hemosiderin deposition was also identified. Large areas of hemorrhagic necrosis were seen in case 1. Tumor cells were immunopositive for chromogranin and synaptophysin, while they were negative for HMB-45. Electron microscopy was performed. A final diagnosis of pigmented pheochromocytoma was rendered in both cases. Pigmented pheochromocytoma is a very rare tumor, which needs to be differentiated from other pigmented tumors like malignant melanoma of adrenal gland and pigmented adrenal adenoma. Histochemistry and immunohistochemistry help in making this distinction.

  10. Immuno-Histochemical and Quantitative Study of Melanocytes and Melanin Granules in Oral Epithelial Dysplasia.

    PubMed

    Honwad, Swapna; Ravi, S V; Donoghue, Mandana; Joshi, Manjiri

    2017-07-01

    Oral Epithelial dysplasia (OED) is a potentially malignant disorder that is characterized by the presence of architectural and cytological changes. One of the prime factors responsible for the development of these lesions is the usage of tobacco. A variety of factors provide protective mechanism in order to prevent the effects of chemotoxic agents including tobacco products of which, melanin pigmentation is one of the vital elements. Role of melanocytes in progression of OED has remained unclear, so the present study was done to evaluate density of melanocyte and melanin granules in different grades of epithelial dysplasia and to correlate both findings with different grades of epithelial dysplasia. The study included 60 OED cases, of which three histopathogical sections were prepared from each block. The sections were stained with Hematoxylin and Eosin, Masson Fontana and Human Melanoma Black (HMB-45), an immunohistochemical stain. Quantification of melanin granules was evaluated under 40X magnification using arbitrary scale with micrometer square as, 0= Absence of melanin granules, 1= Rare and scattered melanin granules, 2= Dense but not aggregated melanin granules, 3= Dense and aggregated melanin granules. Density of melanocytes was evaluated under 10X magnification. Five consecutive fields were evaluated for melanocytes and melanin granules starting from the field of highest density. There was an insignificant increase in number of melanocytes and melanin granules in mild and moderate dysplasia compared to normal but significant reduction was observed in severe dysplasia. The decrease in number of melanocytes and melanin granules was proportional to severity of epithelial dysplasia. This could be due to chronic irritation by chemical products leading to death of melanocytes.

  11. Renal cell carcinoma metastatic to the nasal cavity.

    PubMed

    Terada, Tadashi

    2012-01-01

    Metastatic renal cell carcinoma of the nasal cavity is very rare. A 76-year-old man presented with epistaxis and admitted to our hospital. His past histories were right radical nephrectomy for renal cell carcinomas at the age of 68 years and brain infarction at the age of 75 years. Laryngoscopic examination revealed a red polyp of the right nasal cavity. Imaging modalities including CT and MRI also revealed a tumor measuring 2 x 3 x 2 cm. Angiography showed that the tumor is very hypervascular. Clinical diagnosis was angiogenic tumors including hemangioma, sinonasal hemangiopericytoma, and paraganglioma. A blood data showed anemia and low platerets, and bone marrow biopsy revealed myelodysplastic syndrome. A coiling embolization of the feeding artery was performed, and the tumor reduced markedly. The tumor was resected almost entirely. Pathologically, the tumor was 2 x 1.5 x 1.5 cm red tumor. The tumor cells had clear cytoplasm, and arranged in a trabecular pattern lined by a layer of endothelial cells. Atypia is mild. Immunohistochemically, the tumor cells were positive for pancytokeratin (AE1/3, CAM5.2), RCC ma, CD10, and Ki-67 (labeling=20%), but negative for CD34, factor-VIII-related antigen, CEA, EMA, melanosome (HMB45), S100 protein, p53, and HepPar-1. The pathological diagnosis was made without knowledge of kidney status. A pathological diagnosis of metastatic renal cell carcinoma of clear cell type (grade 1) was made. The patient is now free from tumor, and palliative chemoradiation is considered.

  12. Oncocytic variant of malignant gastrointestinal neuroectodermal tumor: a potential diagnostic pitfall.

    PubMed

    Boland, Jennifer M; Folpe, Andrew L

    2016-11-01

    Malignant gastrointestinal neuroectodermal tumor (MGNET) is a very rare, aggressive malignant neoplasm that may occur in any location in the gastrointestinal tract. Malignant gastrointestinal neuroectodermal tumors typically consist of sheet-like to pseudopapillary proliferation of primitive-appearing epithelioid cells with a moderate amount of lightly eosinophilic cytoplasm, round nuclei and small nucleoli, often in association with osteoclast-like giant cells. By immunohistochemistry, these tumors show expression of S100 protein and SOX10, in the absence of expression of more specific melanocytic markers (eg, HMB45, Melan A). Genetically, malignant gastrointestinal neuroectodermal tumors are characterized by rearrangements of the EWSR1 or FUS genes with CREB1 or ATF1. We report a case of gastric malignant gastrointestinal neuroectodermal tumor occurring in a 46-year-old woman and showing striking oncocytic cytoplasmic change, a previously undescribed potential diagnostic pitfall. An initial needle biopsy showed large, eosinophilic cells with S100 protein and SOX10 expression and lacking expression of KIT, DOG1, Melan A, keratin, chromogranin, or smooth muscle actin, and was interpreted as representing a granular cell tumor. The subsequent excision specimen showed similar-appearing areas, but also contained small more primitive-appearing areas, lacking oncocytic change and having high nuclear grade and brisk mitotic activity. This resection specimen was initially diagnosed as a malignant granular cell tumor. However subsequent gene expression profiling studies showed an EWSR1-ATF1 fusion, confirmed with fluorescence in situ hybridization for EWSR1, and a final diagnosis of MGNET with oncocytic change was made. This case highlights a previously undescribed pitfall in the diagnosis of MGNET, oncocytic change, and suggests that MGNET should be included in the differential diagnosis for unusual oncocytic neoplasms of the gastrointestinal tract.

  13. A systematic review on the role of vitamins, minerals, proteins, and other supplements for the treatment of cachexia in cancer: a European Palliative Care Research Centre cachexia project

    PubMed Central

    Mochamat; Cuhls, Henning; Marinova, Milka; Kaasa, Stein; Stieber, Christiane; Conrad, Rupert; Radbruch, Lukas

    2016-01-01

    Abstract We provide a systematic review to support the European Palliative Care Research Collaboration development of clinical guidelines for cancer patients suffering from cachexia. CENTRAL, MEDLINE, PsycINFO, ClinicalTrials.gov, and a selection of cancer journals have been searched up until 15 April 2016. The systematic literature research yielded 4214 publications with 21 of these included in the final evaluation. Regarding minerals, our search identified only one study examining the use of magnesium with no effect on weight loss. As far as vitamins are concerned, vitamin E in combination with omega‐3 fatty acids displayed an effect on survival in a single study, vitamin D showed improvement of muscle weakness in prostate cancer patients, and vitamin C supplementation led to an improvement of various quality of life aspects in a sample with a variety of cancer diagnoses. For proteins, a combination therapy of β‐hydroxy‐β‐methylbutyrate (HMB), arginine, and glutamine showed an increase in lean body mass after 4 weeks in a study of advanced solid tumour patients, whereas the same combination did not show a benefit on lean body mass in a large sample of advanced lung and other cancer patients after 8 weeks. L‐carnitine led to an increase of body mass index and an increase in overall survival in advanced pancreatic cancer patients. Adverse effects of food supplementation were rare and showed mild intensity. There is not enough solid evidence for the use of minerals, vitamins, proteins, or other supplements in cancer. No serious adverse effects have been reported with dietary supplementation. PMID:27897391

  14. Molecular confirmation of t(6;11)(p21;q12) renal cell carcinoma in archival paraffin-embedded material using a break-apart TFEB FISH assay expands its clinicopathologic spectrum.

    PubMed

    Argani, Pedram; Yonescu, Raluca; Morsberger, Laura; Morris, Kerry; Netto, George J; Smith, Nathan; Gonzalez, Nilda; Illei, Peter B; Ladanyi, Marc; Griffin, Constance A

    2012-10-01

    A subset of renal cell carcinomas (RCCs) is characterized by t(6;11)(p21;q12), which results in fusion of the untranslated Alpha (MALAT1) gene to the TFEB gene. Only 21 genetically confirmed cases of t(6;11) RCCs have been reported. This neoplasm typically demonstrates a distinctive biphasic morphology, comprising larger epithelioid cells and smaller cells clustered around basement membrane material; however, the full spectrum of its morphologic appearances is not known. The t(6;11) RCCs differ from most conventional RCCs in that they consistently express melanocytic immunohistochemical (IHC) markers such as HMB45 and Melan A and the cysteine protease cathepsin K but are often negative for epithelial markers such as cytokeratins. TFEB IHC has been proven to be useful to confirm the diagnosis of t(6;11) RCCs in archival material, because native TFEB is upregulated through promoter substitution by the gene fusion. However, IHC is highly fixation dependent and has been proven to be particularly difficult for TFEB. A validated fluorescence in situ hybridization (FISH) assay for molecular confirmation of the t(6;11) RCC in archival formalin-fixed, paraffin-embedded material has not been previously reported. We report herein the development of a break-apart TFEB FISH assay for the diagnosis of t(6;11)(p21;q12) RCCs. We validated the assay on 4 genetically confirmed cases and 76 relevant expected negative control cases and used the assay to report 8 new cases that expand the clinicopathologic spectrum of t(6;11) RCCs. An additional previously reported TFEB IHC-positive case was confirmed by TFEB FISH in 46-year-old archival material. In conclusion, TFEB FISH is a robust, clinically validated assay that can confirm the diagnosis of t(6;11) RCC in archival material and should allow a more comprehensive clinicopathologic delineation of this recently recognized neoplastic entity.

  15. A "tumour trifecta:" myelolipomata arising within an adrenocortical adenoma ipsilateral to a synchronous clear cell renal cell carcinoma.

    PubMed

    Mahe, Etienne; El-Shinnawy, Ihab

    2010-12-01

    We present an intriguing case of adrenal myelolipomata occurring within an adrenocortical adenoma in concert with an ipsilateral clear cell renal cell carcinoma. A 50-year-old female presented with dull right flank pain and hematuria. Computed tomography indicated a 2.5 cm right renal mass as well as a 5 cm right adrenal mass. Both masses were surgically resected concurrently. Histology of the renal mass was consistent with conventional clear cell renal cell carcinoma, Fuhrman grade III. There was no extra-renal extension or lymphovascular invasion. The adrenal mass was a cortical adenoma with solid and nested patterns, with discrete zones consisting of erythroid, myeloid and megakaryocytic cells intermixed with mature adipocytes. Mitoses were inconspicuous. The solid tumour component was strongly positive for vimentin, inhibin and CD56, focally positive for low-molecular-weight cytokeratin (Cam 5.2), calretinin and CD10 (chiefly in the myelolipomatous zones), and negative for chromogranin, S100, HMB-45, melan-A (A103), Mart-1, synaptophysin, SMA, CK7, CK20, ER, PR, TTF-1, CD99 and GCDFP (BRST-2). Ki67 (MIB1) staining indicated a low tumour proliferation index. Although well-described individually, a search of the English language literature suggests that this is the first such documented case of synchrony of these three lesions. We also present a relevant review of the literature pertaining to adrenal lesions. In particular, we emphasize the epidemiological, histological and immunohistochemical features that are helpful in determining the origin and malignant potential of adrenal lesions.

  16. Diagnostic Approach to Eosinophilic Renal Neoplasms

    PubMed Central

    Kryvenko, Oleksandr N.; Jorda, Merce; Argani, Pedram; Epstein, Jonathan I.

    2015-01-01

    Context Eosinophilic renal neoplasms include a spectrum of solid and papillary tumors ranging from indolent benign oncocytoma to highly aggressive malignancies. Recognition of the correct nature of the tumor, especially in biopsy specimens, is paramount for patient management. Objective To review the diagnostic approach to eosinophilic renal neoplasms with light microscopy and ancillary techniques. Data Sources Review of the published literature and personal experience. Conclusions The following tumors are in the differential diagnosis of oncocytic renal cell neoplasm: oncocytoma, chromophobe renal cell carcinoma (RCC), hybrid tumor, tubulocystic carcinoma, papillary RCC, clear cell RCC with predominant eosinophilic cell morphology, follicular thyroid-like RCC, hereditary leiomyomatosis–associated RCC, acquired cystic disease–associated RCC, rhabdoid RCC, microphthalmia transcription factor translocation RCC, epithelioid angiomyolipoma, and unclassified RCC. In low-grade nonpapillary eosinophilic neoplasms, distinction between oncocytoma and low-grade RCC mostly rests on histomorphology; however, cytokeratin 7 immunostain may be helpful. In high-grade nonpapillary lesions, there is more of a role for ancillary techniques, including immunohistochemistry for cytokeratin 7, CA9, CD10, racemase, HMB45, and Melan-A. In papillary eosinophilic neoplasms, it is important to distinguish sporadic type 2 papillary RCC from microphthalmia transcription factor translocation and hereditary leiomyomatosis–associated RCC. Histologic and cytologic features along with immunohistochemistry and fluorescence in situ hybridization tests for TFE3 (Xp11.2) and TFEB [t(6;11)] are reliable confirmatory tests. Eosinophilic epithelial neoplasms with architecture, cytology, and/or immunoprofile not qualifying for either of the established types of RCC should be classified as unclassified eosinophilic RCC and arbitrarily assigned a grade (low or high). PMID:25357116

  17. Quantification of β-hydroxymethylbutyrate and leucine by ultrahigh performance liquid chromatography tandem mass spectrometry at different situations and stages of a rodent life.

    PubMed

    Santos-Fandila, A; Bueno-Vargas, P; Zafra-Gómez, A; López-Pedrosa, J M; Ramírez, M

    2015-07-15

    The main objective of this work was to develop a method to measure Leucine (Leu) and β-hydroxymethylbutyrate (HMB) at basal levels in serum, urine, milk and brain microdialysates in rats. Ultrahigh performance liquid chromatography-electrospray-tandem mass spectrometry (UHPLC-ESI-MS/MS) was used as analytical technique. The sample treatment was simple and consisted of dilution with methanol and centrifugation for serum and urine, dilution with water and filtration with an Amicon filter for milk, and treatment with formic acid with no further dilution for microdialyzates. The procedures for sampling and the UHPLC-MS/MS parameters were accurately optimized to achieve the highest recoveries and to enhance the analytical characteristics of the method. For chromatographic separation, an Acquity UPLC BEH Amide column using acetonitrile-water gradient with formic acid as additive was used. The total run time was 4min. The analytical characteristics (accuracy, selectivity and sensitivity) of the proposed method were evaluated. The limits of detection (LODs) obtained ranged from 0.4 to 7ngmL(-1) and the limits of quantification (LOQs) from 1 to 22ngmL(-1). Precision, expressed as relative standard deviation (% RSD), was lower than 15% in all cases, and the determination coefficient (R(2)) was equal or higher than 99.0% with a residual deviation for each calibration point lower than ±25%. Mean recoveries were between 85 and 115%. The method was successfully applied to these matrices being able to detect significant differences between physiological situations, strains and stages of life.

  18. Melanotic Schwannoma of the Cervical Spine Progressing With Pulmonary Metastasis: Case Report

    PubMed Central

    Faria, Mário Henrique Girão; Dória-Netto, Ricardo Henrique; Osugue, Gustavo Jun; Queiroz, Luciano de Souza; Chaddad-Neto, Feres Eduardo

    2013-01-01

    Melanotic schwannoma (MS) is an unusual variant of nerve sheath neoplasm. Only 10% of these tumors will undergo malignant degeneration, with exceedingly rare reported metastasis. We present a 32-year-old woman with a 6-month history of cervical pain and left arm progressive weakness. Neurological examination showed a left upper limb radicular pain, with pyramidal syndrome at C5 level. The magnetic resonance imaging (MRI) study highlighted an intradural extramedullary heterogeneous mass along the spinal cord at the C4–C5 level, slightly hyperintense with T1 and hypointense with T2-weighted sequences, invading the left neural foramen. The patient underwent C3–C5 laminectomy with total resection of a black tumor. In the postoperative period, a patent deficit of shoulder abduction ensued related to the nervous section. Microscopically, compactly fascicles of spindle-shaped cells with pleomorphic and hypercromatic nuclei, dark brown intracellular pigments, as well as some mitotic figures were seen. Immunohistochemical stains for S-100, Human Melanoma Black-45 (HMB-45), and vimentin were positive, with Ki-67 labelling index (LI) of 15% compatible with MS. Six months after radiotherapy she presents local recurrence and lung metastatic dissemination of the MS. She underwent left pulmonary segmentectomy, followed by chemotherapy and radiosurgery. The patient developed a febrile neutropenia and worsening of general status, and died after 3 months due to respiratory complications. MS are rare tumors with potential for local recurrence and distal metastasis. Complete surgical resection remains as the treatment of choice, once the uncommon cases with malignant progression shows low response to chemo and radiotherapy. PMID:24077273

  19. Seismic stratigraphy and depositional history of late Quaternary deposits at the eastern Yellow Sea shelf

    NASA Astrophysics Data System (ADS)

    Yoo, Dong-Geun; Lee, Gwang-Soo; Kim, Gil-Young; Chang, Se-Won; Kim, Kyoung-Jin

    2017-04-01

    The late Quaternary stratigraphy and sedimentation at the eastern Yellow Sea shelf was studied using a dense network of high-resolution, single-channel seismic reflection profiles and sediment data. The shelf sequence in this area consists of six seismic units formed since the LGM. During the LGM, the study area was completely exposed, resulting in subaerial erosion associated with paleo-channel incision by the Huanghe and Korean Rivers. As the shelf was flooded, the incised channels were backfilled fluvial or coastal sediments, forming incised channel-fill deposits (SU1). The paleo-river may have supplied abundant terrigenous sediments to the study area around the paleo-river mouth and adjacent area. These sediments were trapped within the paleo-estuary and formed SU2, regarded as an estuarine deposit. Two types of serial sand ridges (SU3 and SU5) which correspond to transgressive deposits developed. SU3 on the southern part, west of Jeju Island (80 110 m deep) is regarded as a moribund-type mainly formed during the early to middle stage of transgression. These are thought to have ceased growing and remobilizing. In contrast, SU5 (occurring 30 50 m deep off the Korean Peninsula) is generally regarded as active sand ridges deposited during the late stage of transgression and is partly modified by modern tidal currents. As the transgression continued, the near-surface sediments were reworked and redistributed by shelf erosion, resulting in a thin veneer of transgressive sands (SU4). The uppermost unit (SU6) formed the Heuksan Mud Belt (HMB), which is one of the most prominent mud deposits in the Yellow Sea. The lower part of the HMD corresponds to shelf-mud deposited during the late stage of transgression, whereas the upper part consists of a recent shelf-delta developed after the highstand sea level at about 7 ka BP.

  20. Osteoprotegerin Contributes to the Metastatic Potential of Cells with a Dysfunctional TSC2 Tumor-Suppressor Gene

    PubMed Central

    Steagall, Wendy K.; Pacheco-Rodriguez, Gustavo; Glasgow, Connie G.; Ikeda, Yoshihiko; Lin, Jing-Ping; Zheng, Gang; Moss, Joel

    2014-01-01

    In addition to its effects on bone metabolism, osteoprotegerin (OPG), a soluble member of the tumor necrosis factor family of receptors, promotes smooth muscle cell proliferation and migration and may act as a survival factor for tumor cells. We hypothesized that these cellular mechanisms of OPG may be involved in the growth and proliferation of lymphangioleiomyomatosis (LAM) cells, abnormal smooth muscle-like cells with mutations in one of the tuberous sclerosis complex tumor-suppressor genes (TSC1/TSC2) that cause LAM, a multisystem disease characterized by cystic lung destruction, lymphatic infiltration, and abdominal tumors. Herein, we show that OPG stimulated proliferation of cells cultured from explanted LAM lungs, and selectively induced migration of LAM cells identified by the loss of heterozygosity for TSC2. Consistent with these observations, cells with TSC2 loss of heterozygosity expressed the OPG receptors, receptor activator of NF-κB ligand, syndecan-1, and syndecan-2. LAM lung nodules showed reactivities to antibodies to tumor necrosis factor–related apoptosis-inducing ligand, receptor activator of NF-κB ligand, syndecan-1, and syndecan-2. LAM lung nodules also produced OPG, as shown by expression of OPG mRNA and colocalization of reactivities to anti-OPG and anti-gp100 (HMB45) antibodies in LAM lung nodules. Serum OPG was significantly higher in LAM patients than in normal volunteers. Based on these data, it appears that OPG may have tumor-promoting roles in the pathogenesis of lymphangioleiomyomatosis, perhaps acting as both autocrine and paracrine factors. PMID:23867796

  1. Detection of toxin proteins from Bacillus thuringiensis strain 4.0718 by strategy of 2D-LC-MS/MS.

    PubMed

    Yang, Qi; Tang, Sijia; Rang, Jie; Zuo, Mingxing; Ding, Xuezhi; Sun, Yunjun; Feng, Pinghui; Xia, Liqiu

    2015-04-01

    Bacillus thuringiensis is a kind of insecticidal microorganism which can produce a variety of toxin proteins, it is particularly important to find an effective strategy to identify novel toxin proteins rapidly and comprehensively with the discovery of the wild-type strains. Multi-dimensional high-performance liquid chromatography combined with mass spectrometry has become one of the main methods to detect and identify toxin proteins and proteome of B. thuringiensis. In this study, protein samples from B. thuringiensis strain 4.0718 were analyzed on the basis of two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS), and tryptic peptides of whole cell from the late sporulation phase were eluted at different concentration gradients of ammonium chloride and followed by secondary mass spectrum identification. 831 and 894 proteins were identified from two biological replicates, respectively, while 1,770 and 1,859 peptides were detected correspondingly. Among the identified proteins and peptides, 606 proteins and 1,259 peptides were detected in both replicates, which mean that 1,119 proteins and 2,370 peptides were unique to the proteome of this strain. A total of 15 toxins have been identified successfully, and seven of them were firstly discovered in B. thuringiensis strain 4.0718 that were Crystal protein (A1E259), pesticidal protein (U5KS09), Cry2Af1 (A4GVF0), Cry2Ad (Q9RM89), Cry1 (K4HMB5), Cry1Bc (Q45774), and Cry1Ga (Q45746). The proteomic strategy employed in the present study has provided quick and exhaustive identification of toxins produced by B. thuringiensis.

  2. Muse Cells Derived from Dermal Tissues Can Differentiate into Melanocytes.

    PubMed

    Tian, Ting; Zhang, Ru-Zhi; Yang, Yu-Hua; Liu, Qi; Li, Di; Pan, Xiao-Ru

    2017-02-07

    The objective of the authors has been to obtain multilineage-differentiating stress-enduring cells (Muse cells) from primary cultures of dermal fibroblasts, identify their pluripotency, and detect their ability to differentiate into melanocytes. The distribution of SSEA-3-positive cells in human scalp skin was assessed by immunohistochemistry, and the distribution of Oct4, Sox2, Nanog, and SSEA-3-positive cells was determined by immunofluorescence staining. The expression levels of Sox2, Oct4, hKlf4, and Nanog mRNAs and proteins in Muse cells were determined by reverse transcription polymerase chain reaction (RT-PCR) analyses and Western blots, respectively. These Muse cells differentiated into melanocytes in differentiation medium. The SSEA-3-positive cells were scattered in the basement membrane zone and the dermis, with comparatively more in the sebaceous glands, vascular and sweat glands, as well as the outer root sheath of hair follicles, the dermal papillae, and the hair bulbs. Muse cells, which have the ability to self-renew, were obtained from scalp dermal fibroblasts by flow cytometry sorting with an anti-SSEA-3 antibody. The results of RT-PCR, Western blot, and immunofluorescence staining showed that the expression levels of Oct4, Nanog, Sox2, and Klf4 mRNAs and proteins in Muse cells were significantly different from their parental dermal fibroblasts. Muse cells differentiated into melanocytes when cultured in melanocyte differentiation medium, and the Muse cell-derived melanocytes expressed the melanocyte-specific marker HMB45. Muse cells could be obtained by flow cytometry from primary cultures of scalp dermal fibroblasts, which possessed the ability of pluripotency and self-renewal, and could differentiate into melanocytes in vitro.

  3. Insect bite reactions.

    PubMed

    Singh, Sanjay; Mann, Baldeep Kaur

    2013-01-01

    Insects are a class of living creatures within the arthropods. Insect bite reactions are commonly seen in clinical practice. The present review touches upon the medically important insects and their places in the classification, the sparse literature on the epidemiology of insect bites in India, and different variables influencing the susceptibility of an individual to insect bites. Clinical features of mosquito bites, hypersensitivity to mosquito bites Epstein-Barr virus NK (HMB-EBV-NK) disease, eruptive pseudoangiomatosis, Skeeter syndrome, papular pruritic eruption of HIV/AIDS, and clinical features produced by bed bugs, Mexican chicken bugs, assassin bugs, kissing bugs, fleas, black flies, Blandford flies, louse flies, tsetse flies, midges, and thrips are discussed. Brief account is presented of the immunogenic components of mosquito and bed bug saliva. Papular urticaria is discussed including its epidemiology, the 5 stages of skin reaction, the SCRATCH principle as an aid in diagnosis, and the recent evidence supporting participation of types I, III, and IV hypersensitivity reactions in its causation is summarized. Recent developments in the treatment of pediculosis capitis including spinosad 0.9% suspension, benzyl alcohol 5% lotion, dimethicone 4% lotion, isopropyl myristate 50% rinse, and other suffocants are discussed within the context of evidence derived from randomized controlled trials and key findings of a recent systematic review. We also touch upon a non-chemical treatment of head lice and the ineffectiveness of egg-loosening products. Knockdown resistance (kdr) as the genetic mechanism making the lice nerves insensitive to permethrin is discussed along with the surprising contrary clinical evidence from Europe about efficacy of permethrin in children with head lice carrying kdr-like gene. The review also presents a brief account of insects as vectors of diseases and ends with discussion of prevention of insect bites and some serious adverse effects

  4. A systematic review on the role of vitamins, minerals, proteins, and other supplements for the treatment of cachexia in cancer: a European Palliative Care Research Centre cachexia project.

    PubMed

    Mochamat; Cuhls, Henning; Marinova, Milka; Kaasa, Stein; Stieber, Christiane; Conrad, Rupert; Radbruch, Lukas; Mücke, Martin

    2017-02-01

    We provide a systematic review to support the European Palliative Care Research Collaboration development of clinical guidelines for cancer patients suffering from cachexia. CENTRAL, MEDLINE, PsycINFO, ClinicalTrials.gov, and a selection of cancer journals have been searched up until 15 April 2016. The systematic literature research yielded 4214 publications with 21 of these included in the final evaluation. Regarding minerals, our search identified only one study examining the use of magnesium with no effect on weight loss. As far as vitamins are concerned, vitamin E in combination with omega-3 fatty acids displayed an effect on survival in a single study, vitamin D showed improvement of muscle weakness in prostate cancer patients, and vitamin C supplementation led to an improvement of various quality of life aspects in a sample with a variety of cancer diagnoses. For proteins, a combination therapy of β-hydroxy-β-methylbutyrate (HMB), arginine, and glutamine showed an increase in lean body mass after 4 weeks in a study of advanced solid tumour patients, whereas the same combination did not show a benefit on lean body mass in a large sample of advanced lung and other cancer patients after 8 weeks. L-carnitine led to an increase of body mass index and an increase in overall survival in advanced pancreatic cancer patients. Adverse effects of food supplementation were rare and showed mild intensity. There is not enough solid evidence for the use of minerals, vitamins, proteins, or other supplements in cancer. No serious adverse effects have been reported with dietary supplementation.

  5. Oncogene abnormalities in a series of primary melanomas of the sinonasal tract: NRAS mutations and cyclin D1 amplification are more frequent than KIT or BRAF mutations.

    PubMed

    Chraybi, Meriem; Abd Alsamad, Issam; Copie-Bergman, Christiane; Baia, Maryse; André, Jocelyne; Dumaz, Nicolas; Ortonne, Nicolas

    2013-09-01

    Primary malignant melanoma of sinonasal tract is a rare but severe form of melanoma. We retrospectively analyzed 17 cases and focused on the histologic presentation and the expression of c-Kit, epidermal growth factor receptor (EGFR), cyclin D1/Bcl-1, PS100, and HMB45 and searched for BRAF, NRAS, and KIT mutations that are known to be associated with melanoma subtypes, together with amplifications of KIT, cyclin D1, cyclin-dependent kinase 4, MDM2, and microphthalmia-associated transcription factor using quantitative polymerase chain reaction. In most cases (78%), an in situ component was evidenced. Invasive components were composed of diffuse areas of rhabdoid, epithelioid, or spindle cells and, in most cases, lacked inflammatory reaction, suggesting that an immune escape phenomenon probably develops when the disease progresses. EGFR was rarely and weakly expressed in the in situ component of 2 cases. None of the investigated case showed BRAF V600E, but 1 had a D594G mutation. NRAS mutations in exon 2 (G12D or G12A) were found in 3 cases (18%), and a KIT mutation in exon 11 (L576P), in 1, whereas c-Kit was expressed at the protein level in half of the cases. Amplifications of cyclin D1 were evidenced in 5 cases, confirmed in 3 by fluorescence in situ hybridization, but this was not always correlated with protein expression, found in 8 patients (62.5%), 3 having no significant amplification. In conclusion, primary malignant melanoma of sinonasal tract is not associated with BRAF V600E mutations. Instead, NRAS or KIT mutations and cyclin D1 amplification can be found in a proportion of cases, suggesting that primary malignant melanoma of sinonasal tract is heterogeneous at the molecular level and should not be sensitive to therapeutic approaches aiming at BRAF.

  6. Primary mucosal melanoma arising from the eustachian tube with CTLA-4, IL-17A, IL-17C, and IL-17E upregulation

    PubMed Central

    Wei, Calvin; Sirikanjanapong, Sasis; Lieberman, Seth; Delacure, Mark; Martiniuk, Frank; Levis, William; Wang, Beverly Y.

    2013-01-01

    Primary malignant melanoma arising from the eustachian tube is extremely rare. We report the case of a 63-year-old white man who presented with a 1-month history of left-sided hearing loss and aural fullness. Flexible fiberoptic laryngoscopy detected a blue-purple mass that appeared to arise from the left lateral nasopharynx. Computed tomography demonstrated an enhancing mass arising from an orifice of the left eustachian tube. The tumor was debulked endoscopically and was confirmed to have originated in the left eustachian tube. Histologically, the tumor was made up of heavily pigmented pleomorphic spindle cells with frequent mitoses. The tumor cells were immunohistochemically positive for S-100 protein, HMB-45, Melan-A, and PNL-2. The final diagnosis was a mucosal malignant melanoma. We also performed a nested polymerase chain reaction assay for several genes of interest, including CTLA-4, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F, PLZF, Foxp3, RORγt, CD27, and CD70. These genes have been studied mainly in cutaneous melanomas, especially for the development of immunotherapy. But only very limited studies have been done on mucosal melanomas. Our investigation found upregulation of CTLA-4, IL-17A, IL-17C, and IL-17E. Based on our finding of CTLA-4 upregulation, it may be suggested that our patient may have had low antitumor immunity and that he might have benefitted from CTLA-4 blockade. On the other hand, upregulation of IL-17A and IL-17E might reflect increased antitumor immunity, which could suggest that patients with a mucosal melanoma might benefit from immunomodulators associated with the effect of Th17. These genes also have great potential to help melanoma patients obtain tailored treatment, and they can be used as biomarkers for predicting prognosis. PMID:23354891

  7. Transmission of human papillomavirus DNA from patient to surgical masks, gloves and oral mucosa of medical personnel during treatment of laryngeal papillomas and genital warts.

    PubMed

    Ilmarinen, Taru; Auvinen, Eeva; Hiltunen-Back, Eija; Ranki, Annamari; Aaltonen, Leena-Maija; Pitkäranta, Anne

    2012-11-01

    The risk of occupational human papillomavirus (HPV) transmission from patient to medical personnel during laser vaporization procedures remains controversial. The purpose of this study was to determine the risk of HPV transmission from the patient to the protective surgical masks, gloves and oral mucosa of medical personnel during the treatment of laryngeal papillomas and genital warts. The study involved five male patients scheduled for the surgical treatment of laryngeal papillomas, and five male patients undergoing carbon dioxide (CO(2)) laser treatment for urethral warts. Oral mucosa specimens were obtained from the study patients and the employees pre- and postoperatively. Samples were collected from the HPV-infected patient tissue, and from the surgical masks and gloves used by the employees. A total of 120 samples were analyzed for the presence of HPV DNA by PCR, using the degenerated MY09/11/HMB01 primers. After the papilloma procedures, the surgeons' gloves tested HPV positive in one of the five cases and those of the surgical nurse in three of the five cases. After the treatment of genital warts, HPV DNA corresponding to the patient tissue specimens was present in all the samples obtained from the surgical gloves of the operators. All oral mucosa samples obtained from 18 different employees tested HPV negative, as did the surgical mask specimens. According to our study, HPV may contaminate protective equipment, most of all surgical gloves, but transmission of HPV DNA to medical personnel is unlikely to occur provided that protective surgical gloves and masks are applied and disposed of properly.

  8. The effectiveness of the levonorgestrel intrauterine system in obese women with heavy menstrual bleeding.

    PubMed

    Shaw, Valentina; Vandal, Alain C; Coomarasamy, Christin; Ekeroma, Alec J

    2016-12-01

    To evaluate the effectiveness of the levonorgestrel intrauterine system (LNG-IUS) in obese women with heavy menstrual bleeding in Counties Manukau Auckland area, New Zealand. Prospective observational study in a tertiary teaching hospital. Twenty women with heavy menstrual bleeding (HMB) who agreed to treatment with the LNG-IUS and had a body mass index (BMI) of >30 kg/m(2) were recruited between May and December 2014. The women completed two validated tools (Menstrual Impact Questionnaire and the Pictorial Bleeding Assessment Chart) at recruitment, 6 and 12 months follow-up. Demographic, medical and laboratory variables were obtained from the relevant CMH databases. Data on side effects and satisfaction were obtained from the women at 12 months. The median age (range) and BMI of the 20 women were 40.5 years (27-52 years) and 40.6 kg/m(2) (30-68), respectively. Three LNG-IUS were removed due to infection and pain and these women were subsequently booked for a hysterectomy. The reduction in menstrual loss was estimated at 19.7% per month (95% CI (12.5%, 26.2%); P < 0.001), which translates to 73.2% per period of 6 months (95% CI (55.3%, 83.9%)) and 92.8% per period of 12 months (95% CI (80.0%, 97.4%)). The six items in the quality of life measure improved significantly in 14 women but only 12 women were satisfied with the treatment. The LNG-IUS was an effective treatment for 67% of obese women with heavy menstrual bleeding over a 12-month period, as assessed by the reduction in menstrual bleeding and the improvement in the quality of life measures. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  9. Establishment of a novel clear cell sarcoma cell line (Hewga-CCS), and investigation of the antitumor effects of pazopanib on Hewga-CCS.

    PubMed

    Outani, Hidetatsu; Tanaka, Takaaki; Wakamatsu, Toru; Imura, Yoshinori; Hamada, Kenichiro; Araki, Nobuhito; Itoh, Kazuyuki; Yoshikawa, Hideki; Naka, Norifumi

    2014-06-19

    Clear cell sarcoma (CCS) is a therapeutically unresolved, aggressive, soft tissue sarcoma (STS) that predominantly affects young adults. This sarcoma is defined by t(12;22)(q13;q12) translocation, which leads to the fusion of Ewing sarcoma gene (EWS) to activating transcription factor 1 (ATF1) gene, producing a chimeric EWS-ATF1 fusion gene. We established a novel CCS cell line called Hewga-CCS and developed an orthotopic tumor xenograft model to enable comprehensive bench-side investigation for intensive basic and preclinical research in CCS with a paucity of experimental cell lines. Hewga-CCS was derived from skin metastatic lesions of a CCS developed in a 34-year-old female. The karyotype and chimeric transcript were analyzed. Xenografts were established and characterized by morphology and immunohistochemical reactivity. Subsequently, the antitumor effects of pazopanib, a recently approved, novel, multitargeted, tyrosine kinase inhibitor (TKI) used for the treatment of advanced soft tissue sarcoma, on Hewga-CCS were assessed in vitro and in vivo. Hewga-CCS harbored the type 2 EWS-ATF1 transcript. Xenografts morphologically mimicked the primary tumor and expressed S-100 protein and antigens associated with melanin synthesis (Melan-A, HMB45). Pazopanib suppressed the growth of Hewga-CCS both in vivo and in vitro. A phospho-receptor tyrosine kinase array revealed phosphorylation of c-MET, but not of VEGFR, in Hewga-CCS. Subsequent experiments showed that pazopanib exerted antitumor effects through the inhibition of HGF/c-MET signaling. CCS is a rare, devastating disease, and our established CCS cell line and xenograft model may be a useful tool for further in-depth investigation and understanding of the drug-sensitivity mechanism.

  10. Establishment of a novel clear cell sarcoma cell line (Hewga-CCS), and investigation of the antitumor effects of pazopanib on Hewga-CCS

    PubMed Central

    2014-01-01

    Background Clear cell sarcoma (CCS) is a therapeutically unresolved, aggressive, soft tissue sarcoma (STS) that predominantly affects young adults. This sarcoma is defined by t(12;22)(q13;q12) translocation, which leads to the fusion of Ewing sarcoma gene (EWS) to activating transcription factor 1 (ATF1) gene, producing a chimeric EWS-ATF1 fusion gene. We established a novel CCS cell line called Hewga-CCS and developed an orthotopic tumor xenograft model to enable comprehensive bench-side investigation for intensive basic and preclinical research in CCS with a paucity of experimental cell lines. Methods Hewga-CCS was derived from skin metastatic lesions of a CCS developed in a 34-year-old female. The karyotype and chimeric transcript were analyzed. Xenografts were established and characterized by morphology and immunohistochemical reactivity. Subsequently, the antitumor effects of pazopanib, a recently approved, novel, multitargeted, tyrosine kinase inhibitor (TKI) used for the treatment of advanced soft tissue sarcoma, on Hewga-CCS were assessed in vitro and in vivo. Results Hewga-CCS harbored the type 2 EWS-ATF1 transcript. Xenografts morphologically mimicked the primary tumor and expressed S-100 protein and antigens associated with melanin synthesis (Melan-A, HMB45). Pazopanib suppressed the growth of Hewga-CCS both in vivo and in vitro. A phospho-receptor tyrosine kinase array revealed phosphorylation of c-MET, but not of VEGFR, in Hewga-CCS. Subsequent experiments showed that pazopanib exerted antitumor effects through the inhibition of HGF/c-MET signaling. Conclusions CCS is a rare, devastating disease, and our established CCS cell line and xenograft model may be a useful tool for further in-depth investigation and understanding of the drug-sensitivity mechanism. PMID:24946937

  11. The in-vitro spheroid culture induces a more highly differentiated but tumorigenic population from melanoma cell lines.

    PubMed

    Mo, Jing; Sun, Baocun; Zhao, Xiulan; Gu, Qiang; Dong, Xueyi; Liu, Zhiyong; Ma, Yuemei; Zhao, Nan; Liu, Yanrong; Chi, Jiadong; Sun, Ran

    2013-08-01

    Cancer stem cells (CSCs) have been identified in various malignancies, and different properties have been examined to characterize CSCs: tumorigenicity in immunocompromised mice, stem cell surface markers, label-retaining properties, and proliferation as nonadherent spheres. This study explored the consistency and efficiency among these methods. Among the melanoma cell lines examined (A375, A875, MUM-2b, and MUM-2c), only A375 and MUM-2c grew as nonadherent spheres and continuously propagated in a defined serum-free medium in vitro. Flow cytometry and immunofluorescence analysis indicated that sphere-derived cells contained a smaller proportion of cells expressing the candidate surface markers of melanoma stem cells such as ABCB5, CD133, CD20 and CD271, and a larger proportion of cells expressing melanocytic differentiation markers such as HMB45 and S100 protein, compared with adherent cells. Surprisingly, the more highly differentiated sphere-derived melanoma cells exhibited increased tumorigenic potential in vivo, as indicated by shorter tumor incubation (A375) and smaller number of cells required to initiate tumor formation (A375 and MUM-2c) compared with those of parental cells. Despite the similarity in histopathological characteristics, the expression profile indicated that xenografts derived from sphere-derived melanoma cells exhibited a more tumorigenic phenotype with respect to the stem or the differentiation markers detected by immunohistochemical analysis. Therefore, sphere formation in nonadherent cultures may not be a preferred surrogate in-vitro method for enriching melanoma stem cells according to candidate markers but may be a favorable condition for activating potential CSCs.

  12. Prevalence of uterine and adnexal involvement in pulmonary lymphangioleiomyomatosis: a clinicopathologic study of 10 patients.

    PubMed

    Hayashi, Takuo; Kumasaka, Toshio; Mitani, Keiko; Terao, Yasuhisa; Watanabe, Masao; Oide, Takashi; Nakatani, Yukio; Hebisawa, Akira; Konno, Ryo; Takahashi, Kazuhisa; Yao, Takashi; Seyama, Kuniaki

    2011-12-01

    Lymphangioleiomyomatosis (LAM), a systemic disorder affecting almost exclusively young women, is characterized by the abnormal proliferation of smooth muscle-like cells (LAM cells). LAM can occur either in association with the tuberous sclerosis complex (TSC) (TSC-LAM) or without TSC (sporadic LAM). Recent studies have demonstrated that LAM is a neoplasm arising from constitutive activation of the mammalian target of rapamycin signaling pathway dysregulated by a functional loss of TSC genes, but the primary organ of origin remains unclear. Therefore, we performed histologic and immunohistologic analyses of gynecologic organs in 20 patients, half with and the other half without pulmonary LAM, to determine how often LAM involves the uterus. The results showed that 9 of 10 (90%) patients with pulmonary LAM had uterine LAM lesions. In contrast, no patients without pulmonary LAM had so. All uterine LAM lesions were accompanied by LAM lesions in retroperitoneal or pelvic lymph nodes and LAM cell clusters, each enveloped by a monolayer of vascular endothelial growth factor receptor-3-positive lymphatic endothelial cells. Furthermore, when we compared uterine lesions of TSC-LAM with those of sporadic LAM, proliferation of HMB45-positive epithelioid-shaped LAM cells and infiltrates with a tongue-like growth pattern was more prominent in the former, whereas the extent of lymphangiogenesis within the myometrium was greater in the latter. These results indicate that uterine involvement is a common manifestation of LAM, and, possibly, that the uterus or an adjacent locale in the retroperitoneum or pelvic cavity is the primary site of origin of LAM.

  13. Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding.

    PubMed

    Fergusson, Rosalie J; Lethaby, Anne; Shepperd, Sasha; Farquhar, Cindy

    2013-11-29

    Heavy menstrual bleeding (HMB), which includes both menorrhagia and metrorrhagia, is an important cause of ill health in women. Surgical treatment of HMB often follows failed or ineffective medical therapy. The definitive treatment is hysterectomy, but this is a major surgical procedure with significant physical and emotional complications, as well as social and economic costs. Several less invasive surgical techniques (e.g. transcervical resection of the endometrium (TCRE), laser approaches) and various methods of endometrial ablation have been developed with the purpose of improving menstrual symptoms by removing or ablating the entire thickness of the endometrium. The objective of this review is to compare the effectiveness, acceptability and safety of techniques of endometrial destruction by any means versus hysterectomy by any means for the treatment of heavy menstrual bleeding. Electronic searches for relevant randomised controlled trials (RCTs) targeted but were not limited to the following: the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsycINFO and the Cochrane CENTRAL register of trials. Attempts were made to identify trials by examining citation lists of review articles and guidelines and by performing handsearching. Searches were performed in 2007, 2008 and 2013. Included in the review were any RCTs that compared techniques of endometrial destruction by any means with hysterectomy by any means for the treatment of heavy menstrual bleeding in premenopausal women. Two review authors independently searched for studies, extracted data and assessed risk of bias. Risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes were estimated from the data. Outcomes analysed included improvement in menstrual blood loss, satisfaction, change in quality of life, duration of surgery and hospital stay, time to return to work, adverse events and requirements for repeat surgery due to failure

  14. Influence of hormonal contraceptives and the occurrence of stroke: integrative review.

    PubMed

    Lima, Adman Câmara Soares; Martins, Larissa Castelo Guedes; Lopes, Marcos Venícios de Oliveira; Araújo, Thelma Leite de; Lima, Francisca Elisângela Teixeira; Aquino, Priscila de Souza; Moura, Escolástica Rejane Ferreira

    2017-01-01

    To identify scientific evidence regarding the influence of hormonal contraceptive use and the occurrence of stroke. Integrative review of the literature, through database search using the descriptors "contraceptive agents", "contraceptive devices", "contraceptives, Oral" and "Stroke". Original studies in Portuguese, Spanish and English, published in full and available online were included. Studies that did not answer our guiding questions and duplicated studies were excluded. Women using combined oral contraceptives have higher risk of stroke, even with a lower hormonal dosage and different types of progestogen, regardless of the duration of use. The use of contraceptives associated with smoking, hypertension, migraine, hypercholesterolemia, obesity and sedentary lifestyle increases the chance of stroke. Contraceptive patch and vaginal ring are associated to increased risk. Use of combined hormonal contraceptives, except for the injectable and the transdermal ones, increases the chance of occurrence of the event. Progestogen-only contraceptives were considered safe. Identificar evidências científicas acerca da influência do uso de anticoncepcionais hormonais na ocorrência do acidente vascular cerebral (AVC). Revisão integrativa da literatura, com pesquisa em bases de dados, utilizando os descritores "contraceptive agents", "contraceptive devices", "contraceptives, Oral" e "stroke". Foram incluídos artigos originais nos idiomas português, espanhol e inglês, publicados na íntegra e disponíveis eletronicamente. Foram excluídos artigos que não respondiam às questões norteadoras e repetidos. Usuárias de anticoncepcional oral combinado apresentam risco maior de AVC, mesmo com dosagem hormonal menor e diferentes tipos de progestágeno, independente do tempo de uso. A presença associada de tabagismo, hipertensão arterial, enxaqueca, hipercolesterolemia, obesidade e sedentarismo aumenta a chance desse desfecho. Adesivo anticoncepcional e anel vaginal s

  15. Vulnerability of caregivers of the elderly with dementia: a cross-sectional descriptive study.

    PubMed

    Leite, Bruna Silva; Camacho, Alessandra Conceição Leite Funchal; Joaquim, Fabiana Lopes; Gurgel, Jonas Lírio; Lima, Thiago Rodrigues; Queiroz, Raquel Santos de

    2017-01-01

    to evaluate the sociodemographic and clinical profile of the caregivers and its relation with the overburden from the care of the elderly with dementia. a cross-sectional descriptive study; the sample was non-probabilistic, developed with caregivers of elderly people with dementia. The field of investigation was the Health Care Center of the Elderly and their Caregivers (CASIC), in the city of Niterói, Rio de Janeiro, Brazil. Data collection took place from February to June 2016, with the following instruments: a sociodemographic questionnaire and Zarit scale. fifty percent of the caregivers presented moderate overburden; 38% presented little overburden; and 12% moderate/severe overburden. It was observed that the median of weekly care hours increases as the overburden increases. Caregivers with moderate to severe overburden, in the majority, do not share care. it is clear that the overburden of care places the caregiver in conditions of biological and psychological vulnerability. avaliar o perfil sociodemográfico e clínico dos cuidadores e sua relação com a sobrecarga proveniente do cuidado ao idoso com demência. estudo descritivo transversal, a amostra foi do tipo não probabilística, desenvolvida com os cuidadores de idosos com demência. O campo de investigação foi o Centro de Atenção à Saúde do Idoso e seus Cuidadores (CASIC), Niterói, Rio de Janeiro, Brasil. A coleta de dados ocorreu de fevereiro a junho de 2016, com os seguintes instrumentos: questionário sociodemográfico e escala de Zarit. 50% dos cuidadores apresentaram sobrecarga moderada, 38% apresentaram pouca sobrecarga e 12%, sobrecarga moderada/severa. Observou-se que a mediana das horas de cuidados semanais aumenta conforme a sobrecarga aumenta. Cuidadores com sobrecarga de moderada a severa, em caráter majoritário, não dividem o cuidado. Dessa forma, fica claro que a sobrecarga do cuidado coloca o cuidador em condições de vulnerabilidade biológica e psicológica.

  16. [TOXIC RISK ASSESSMENT OF FLUORIDE PRESENCE IN BOTTLED WATER CONSUMPTION IN THE CANARY ISLANDS].

    PubMed

    Jáudenes Marrero, Juan Ramón; Hardisson de la Torre, Arturo; Gutiérrez Fernández, Angel José; Rubio Armendáriz, Carmen; Revert Gironés, Consuelo

    2015-11-01

    Introducción: el flúor, como hormetina, es necesario en el organismo para evitar las caries, pero en cantidades excesivas puede llevar a efectos tóxicos adversos como la fluorosis dental o la fluorosis invalidante. Así, será importante no sobrepasar de forma crónica las IDR (Ingestas Diarias Recomendadas) para cada rango de edad y sexo. Se asume que la principal fuente de aporte de fluoruros es el agua. Objetivos: establecer las concentraciones de fluoruro en determinadas marcas de agua envasada que se consumen en Canarias, para renovar los datos ya desactualizados, y hacer la correspondiente evaluación del riesgo tóxico. Método: se han utilizado 25 muestras de siete marcas registradas y comercializadas diferentes, siendo analizadas mediante determinación potenciométrica con electrodo ion selectivo de fluoruro. Resultados: todas las marcas de agua analizadas cumplen con los criterios de calidad según la legislación actual española, ninguna puede considerarse “agua fluorada” y todas se pueden usar en la preparación de alimentos infantiles. Además, según las ingestas diarias de agua recomendadas por la EFSA para cada rango de edad, no se supera la IDR para ningún individuo mayor de cuatro años ni para ninguna de las marcas de agua analizadas. Conclusiones: las aguas envasadas producidas en Canarias tienen niveles de fluoruro similares a las producidas en la península (todas en un rango de 0,24 a 0,62 mg/L). Los individuos sobre los que recaen las restricciones más amplias de consumo de agua son los menores de un año, pero en cualquier caso, a medida que el individuo crece va aumentando la permisibilidad del aporte de fluoruros (aumenta hasta los 19 años) y, por tanto, aumenta la variedad de aguas envasadas que se pueden consumir sin superar la IDR. En ciertos lugares de la Comunidad Autónoma Canaria sería recomendable consumir agua envasada respecto al agua de abastecimiento público.

  17. Dietary potential renal Acid load in venezuelan children.

    PubMed

    López-Sayers, Mayerling; Bernal, Jennifer; López, Michelle

    2015-05-01

    Objetivo: Determinar y analizar la carga acida potencial renal de la dieta (Potential Renal Acid Load PRAL) y el patron de alimentacion de ninos entre 1 a 6 anos aparentemente sanos. Métodos: Se seleccionaron segun conveniencia a padres de 52 ninos asistentes a una consulta de ninos sanos. La calidad de la dieta y el patron de alimentacion se evaluo mediante un recordatorio de 24 horas y un cuestionario de frecuencia de alimentos. Se calculo la ingesta de macronutrientes y grupos de alimentos, como carnes, lacteos, frutas y verduras. La ingesta de nutrientes se comparo con las recomendaciones de energia y nutrientes. El PRAL se determino segun el metodo de Remer y Manz, para determinar la carga acida de la dieta. Se aplico estadistica descriptiva y correlaciones entre el PRAL, nutrientes y grupos de alimentos. Resultados: La ingesta de proteinas, de leche y de carnes fue elevada, mientras que la ingesta de rutas y hortalizas fue baja. El PRAL fue positivo en 92% de los ninos, se asocio con mayor ingesta de energia, proteinas, grasas, carne y lacteos. La ingesta de proteinas fue > 2,5 g/kg/ dia en 46,2% de los ninos. Los grupos de alimentos con mayor desequilibrio debido a exceso fueron la carne y los productos lacteos, mientras que por deficit fue el grupo de frutas y hortalizas. Conclusión: La dieta se caracteriza por una elevada carga de acido o PRAL, lo que aumenta el riesgo de acidosis sistemica y sus consecuencias metabolicas.

  18. Neuroprotective effects of tibolone against oxidative stress induced by ozone exposure.

    PubMed

    Pinto-Almazán, Rodolfo; Rivas-Arancibia, Selva; Farfán-García, Eunice D; Rodríguez-Martínez, Erika; Guerra-Araiza, Christian

    2014-05-16

    Introduccion. El estres oxidativo aumenta la lipoperoxidacion, produce deficits de memoria y de actividad motora asi como una neurodegeneracion progresiva en el sistema nervioso central. La tibolona es un tratamiento para los sintomas de la menopausia que disminuye los niveles de peroxidacion de lipidos y mejora la memoria y el aprendizaje. Objetivo. Estudiar el efecto de la tibolona sobre la peroxidacion de lipidos, los deficits de memoria y motor en el modelo de estres oxidativo inducido por la exposicion cronica al ozono. Materiales y metodos. Se dividieron aleatoriamente 100 ratas adultas Wistar en 10 grupos: control (C), que recibio aire durante 60 dias; (C + tibolona), aire mas 1 mg/kg de tibolona durante 60 dias; los grupos 3-6, ozono durante 7, 15, 30, y 60 dias; y los grupos 7-10, 1 mg/kg de tibolona durante 7, 15, 30 y 60 dias previo a la exposicion al ozono. Se realizaron pruebas de memoria y motoras y se determino el contenido del 4-hidroxinonenal y de la nitrotirosina por Western blot, asi como la muerte neuronal en el hipocampo. Resultados. La administracion de tibolona disminuyo el contenido de lipidos peroxidados, la oxidacion de proteinas y la muerte neuronal en el hipocampo; mejoro la memoria y previno las alteraciones motoras en los animales expuestos a ozono. Conclusion. Nuestros resultados indican un posible papel neuroprotector de la tibolona como un tratamiento util para prevenir la neurodegeneracion inducida por el estres oxidativo.

  19. A correlação índice espectral vs. luminosidade em QSOs e suas implicações

    NASA Astrophysics Data System (ADS)

    Garcia-Rissmann, A.

    2003-08-01

    Estudos de variabilidade de núcleos ativos já demonstraram ser comum o fato de seu contínuo óptico/UV tornar-se mais "duro" à medida que a luminosidade aumenta. Essa tendência ocorre tanto de forma individual quanto global, e pode ter implicações importantes (1) para estudos fotométricos de variabilidade conduzidos numa banda fixa no referencial do observador, comparando objetos a diferentes redshifts, e (2) no cálculo da correção K, com consequente impacto na determinação de massas de buracos negros e bojos de galáxias hospedeiras (através da relação de Magorrian). Confirmo aqui as correlações positivas entre o índice espectral e a luminosidade óptica, utilizando dados espectroscópicos de 11 QSOs monitorados no Brasil e no Chile, durante ~2 anos. O estudo é complementado com parâmetros extraídos de espectros e de dados fotométricos públicos de quasares. Destaco ainda as diferenças observadas em tais correlações para objetos do tipo radio-loud e radio-quiet. Este projeto é financiado pelo I. Milênio/CNPq.

  20. [Drugs having latex and therapeutic alternatives in hospital formulary].

    PubMed

    Damas Fuentes, Rosa María; Pérez León, Moisés; Piñero González, Marta; Sangil Monroy, Nayra; Molero Gómez, Rafael; Domínguez Lantigua, Pablo

    2015-01-01

    Objetivo: Analizar el contenido en látex de los medicamentos en la guía farmacoterapéutica y establecer alternativas en un hospital de tercer nivel. Método: Se seleccionaron los medicamentos susceptibles de contener látex en su material de acondicionamiento, se solicitó al laboratorio fabricante información y se buscaron posibles alternativas incluidas en guía farmacoterapéutica. Resultados: De las 618 especialidades seleccionadas se obtuvo información escrita del laboratorio para 605 (97.9%) y en ficha técnica para 8. De las 57 (9,2%) especialidades con riesgo en pacientes con alergia al látex se encontró una alternativa en guía para el 43,9%. Conclusiones: Conocer las especialidades con látex aumenta la seguridad en la prescripción, mientras que la disponibilidad de una tabla de equivalencias terapéuticas facilita la validación. Los datos publicados vienen a actualizar la información del contenido en látex de los medicamentos para pacientes y personal sanitario, generalmente escasa y variable.

  1. COST-EFFECTIVENESS OF EARLY NUTRITIONAL THERAPY IN MALNOURISHED ADULT PATIENTS IN A HIGH COMPLEXITY HOSPITAL.

    PubMed

    Giraldo Giraldo, Nubia Amparo; Vásquez Velásquez, Johanna; Roldán Cano, Paula Andrea; Ospina Astudillo, Carolina; Sosa Cardona, Yuliet Paulina

    2015-12-01

    Introducción: la malnutrición hospitalaria es un problema frecuente en el mundo que aumenta las complicaciones, los días de estancia, la mortalidad y los costes sanitarios. Objetivos: el objetivo de este estudio fue establecer la coste-efectividad de la terapia nutricional precoz en pacientes malnutridos en un hospital de alta complejidad. Materiales y métodos: este estudio analítico con valoración económica, incluyó 227 adultos hospitalizados y malnutridos según Valoración Global Subjetiva. La cohorte prospectiva recibió Terapia Nutricional Precoz (TNP), mientras que la cohorte retrospectiva recibió Terapia Nutricional Tardía (TNT). Las medidas del coste- efectividad incluyeron costes por: días de estancia, complicaciones y condición de egreso. Resultados: las cohortes fueron similares en cuanto a características clínicas y demográficas, excepto en la mediana de edad; para la TNP fue 61 años (rango intercuartil [RIQ]: 48-71) y para la TNT fue 55 años (RIQ: 44-67) (p=0,024). La TNP se encontró costo-efectiva en la reducción de los días de estancia hospitalaria (11 días, RIQ: 7-17) en comparación con la TNT (18 días, RIQ: 10-28) (p.

  2. Discos de acresção em sistemas Be-X

    NASA Astrophysics Data System (ADS)

    Lopes de Oliveira, R.; Janot-Pacheco, E.

    2003-08-01

    Alguns fenômenos de outbursts em Be-X sugerem a existência, mesmo que temporária, de um disco de acresção quando da passagem do objeto compacto pelo periastro orbital. Neste trabalho avaliamos a possibilidade de formação do disco de acresção em sistemas Be+estrela de neutrons e Be+anã branca, e a influência da excentricidade orbital na ocorrência deste fenômeno. Utilizamos a expressão analítica para o momento angular específico da matéria constituinte de um meio em expansão lenta, como é o caso do disco circunstelar das estrelas Be, proposta por Wang(1981), sob a condição básica de que o raio de circularização deva ser maior do que o raio de Alfvén. Concluímos que existe um limite para o período orbital do sistema acima do qual não é possível a formação do disco de acresção, e que este valor aumenta para sistemas com excentricidade orbital maior.

  3. PubMed

    Dussaillant, Catalina; Echeverría, Guadalupe; Rozowski, Jaime; Velasco, Nicolás; Arteaga, Antonio; Rigotti, Attilio

    2017-06-05

    El huevo es un alimento que aporta proteína de alta calidad y numerosos nutrientes con potenciales beneficios para la salud. Sin embargo, la aparición de la enfermedad cardiovascular como importante causa de morbilidad y mortalidad en el mundo, junto con la identificación de los niveles elevados de colesterol plasmático como factor de riesgo para esta patología, llevó, en los años 70, a profesionales e instituciones de salud a limitar el consumo de colesterol y, por tanto, de huevo en la población. Hasta la fecha, los análisis de cohortes prospectivas tienden a mostrar que el consumo de hasta un huevo diario no aumenta significativamente el riesgo cardiovascular en la población sana. Sin embargo, esta evidencia no es clara en los pacientes diabéticos y pone en duda que este alimento consumido en cantidades elevadas sea del todo inocuo en esta población en particular. Asimismo, estudios de intervención a corto plazo han mostrado que, en general, el consumo de huevo no afecta negativamente los factores de riesgo cardiovascular en individuos sanos así como en aquellos con enfermedad cardiometabólica. Además, estos estudios sugieren que la incorporación del huevo en la dieta podría traer beneficios adicionales, promoviendo un perfil lipídico menos aterogénico.

  4. ORGANIC INFLAMMATORY RESPONSE TO REDUCED PREOPERATIVE FASTING TIME, WITH A CARBOHYDRATE AND PROTEIN ENRICHED SOLUTION; A RANDOMIZED TRIAL.

    PubMed

    de Andrade Gagheggi Ravanini, Guilherme; Portari Filho, Pedro Eder; Abrantes Luna, Renato; Almeida de Oliveira, Vinicius

    2015-08-01

    Introducción: El objetivo de este estudio es la evaluación de la respuesta inflamatoria orgánica a la colecistectomía laparoscópica mediante vídeo con una reducción del tiempo de ayuno preoperatorio a 2h y empleando una solución enriquecida con carbohidratos y proteínas. Métodos: Se trata de un estudio aleatorizado, prospectivo con pacientes divididos en los dos grupos siguientes: grupo A, ayuno convencional y grupo B, ayuno abreviado de 2h con ingesta oral de una solución enriquecida con carbohidratos y proteínas. Antes de la ingesta de la solución, se hicieron mediciones de glucosa sérica, insulina, interleucina 1y TNF-α; también se realizaron mediciones durante la inducción de la anestesia y 4h después de la intervención quirúrgica. Resultados: Treinta y ocho pacientes completaron el estudio sin presentar complicaciones pulmonares relacionadas con el broncoaspirado. La varianza HOMA-IR postoperatoria fue superior en el grupo A (p = 0,001). Conclusión: La reducción del tiempo de ayuno preoperatorio a 2h, empleando soluciones enriquecidas con carbohidratos y proteínas, es segura, reduce la resistencia a la insulina, y no aumenta el riesgo de broncoaspirado.

  5. A comparison of two questionnaires on Informed Consent for extended criteria liver donors.

    PubMed

    Bruzzone, Paolo; Giannarelli, Diana

    2015-01-01

    Un questionario riguardante il consenso informato del ricevente per i cosiddetti donatori marginali di fegato (“extended criteria donors”-ECD) è stato inviato, previa approvazione del Comitato Etico, via e-mail ai membri di 2 società scientifiche, ELPAT(Ethical,Legal and Psychologic Aspects of Organ Transplantation) ed ELITA (European Liver and Intestine Transplant Association)-ELTR(European Liver Transplant Registry). I risultati sono stati pubblicati in diversi lavori apparsi su Transplantation Proceedings. Analizzando statisticamente le tabelle negli articoli 2011 ELPAT e 2013 ELITA, nel lavoro più recente meno Centri Trapianto di fegato (LTC) hanno considerato l’età fino a 80 anni (p<.002) e SGOT>90 IU (p<.02), o tutti i criteri insieme (p<.0001), come indicatori di donatore marginale. Ciò potrebbe riflettere il fatto che nel tempo i LTC sono divenuti meno selettivi, a causa della crescente mortalità dei pazienti in lista di attesa. Considerando che in tutti i nostri studi abbiamo riscontrato un notevole ricorso agli ECD, è necessario che i pazienti ricevano tutte le informazioni che vogliano richiedere sia al momento dell’iscrizione in lista di attesa, sia quando il fegato di un donatore venga effettivamente loro proposto. E’ anche possibile creare una lista di attesa separata, per pazienti che non accettano ECD: tale scelta però ritarda in modo inevitabile il trapianto e quindi, potenzialmente, aumenta la mortalità in lista di attesa.

  6. [Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain].

    PubMed

    Domínguez, Alazne; Álvarez, Antonia; Suárez-Merino, Blanca; Goñi-de-Cerio, Felipe

    2014-03-01

    Introduccion. La incidencia de enfermedades del sistema nervioso central (SNC) aumenta a causa del envejecimiento de la sociedad. Desgraciadamente, los tratamientos clasicos para tratarlas no resultan efectivos debido a la presencia de la barrera hematoencefalica. Objetivo. Abordar las propiedades de la barrera hematoencefalica que impiden el transporte de los farmacos al cerebro y las principales estrategias para tratar las afecciones neurologicas. Desarrollo. La barrera hematoencefalica esta compuesta principalmente por un endotelio vascular especializado y las celulas de la glia. Esta constituye una herramienta a disposicion del organismo para aislar al SNC del resto del cuerpo. Sin embargo, tambien supone un impedimento para que muchos farmacos alcancen su diana en el cerebro. Conclusiones. Para poder tratar las afecciones neurologicas, los farmacos deben ser capaces de alcanzar el cerebro. Los agentes terapeuticos pueden diseñarse para que sean capaces de atravesar esta barrera, o bien facilitar su entrada mediante el uso de sistemas de liberacion. Para evaluar la efectividad de los tratamientos dirigidos a enfermedades del SNC, se emplean los modelos animales de enfermedades neurologicas asi como modelos in vitro de barrera hematoencefalica.

  7. Uso de Sustancias en Mujeres con Desventaja Social: Riesgo para el Contagio de VIH/SIDA

    PubMed Central

    Cianelli, R.; Ferrer, L; Bernales, M.; Miner, S.; Irarrázabal, L.; Molina, Y.

    2009-01-01

    Antecedentes La caracterización epidemiológica en Chile apunta a feminización, pauperización y heterosexualización de la epidemia del VIH, lo que implica un mayor riesgo para las mujeres en desventaja social. Si a esto se suma la utilización de sustancias, la vulnerabilidad de este grupo frente al VIH/SIDA aumenta. Objetivo Describir el uso de sustancias en mujeres con desventaja social e identificar factores de riesgo de contagio de VIH, asociados a este consumo. Material y Método 52 mujeres fueron entrevistadas como parte del proyecto “Testeando una intervención en prevención de VIH/SIDA en mujeres chilenas” GRANT # RO1 TW 006977. Se describen variables sociodemográficas y de consumo de sustancias a través de estadísticas descriptivas y se analiza la relación entre variables a través de pruebas de correlación. Resultados Los resultados indican un perfil sociodemográfico que sitúa a las mujeres en situación de vulnerabilidad frente al contagio de VIH/SIDA, con alto índice de uso de sustancias que acentúa el riesgo. Conclusiones Los hallazgos apuntan a la necesidad de considerar intervenciones que se enfoquen en la prevención de VIH en mujeres, abordando los riesgos asociados al consumo de sustancias. PMID:21197380

  8. Effects of multi-ingredient supplementation on resistance training in young males

    PubMed Central

    Willems, Mark ET; Sallis, Chris W; Haskell, Jonathan A

    2012-01-01

    Muscle strength and fatigue resistance increases with resistance training. Resistance training adaptations can be enhanced with single-ingredient or dual-ingredient supplementation but less is known about resistance training adaptations by multi-ingredient supplementation. We examined the effects of a commercial multi-ingredient supplement on resistance training adaptations for training-specific and non-training-specific tasks in young males. Male participants (n = 16, age 21±2 years, body mass 74.5±5.9 kg, body height 177±5 cm) had at least 1 year experience with resistance training exercises. Training (7 muscle groups, 4 sessions/week, weekly adjustments) consisted of two 6 weeks blocks with 4 weeks between blocks. During training, participants consumed placebo (i.e. maltodextrin, n = 7) or the sports nutritional supplement Cyclone (Maximuscle Ltd, UK, n = 9) (main ingredients creatine monohydrate, whey protein, glutamine and HMB) twice daily with one intake <15 min following a training session. Unpaired Student’s t-test was used for placebo and Cyclone group comparison of percentage changes with p < 0.05. Effect sizes (Cohen’s d) were calculated for the Cyclone group. Cyclone did not enhance maximal voluntary isometric force (MVIF) (p = 0.56), time to fatigue at 70% MVIF (p = 0.41) and peak concentric strength (60°·s−1) (p = 0.66) of m.quadriceps femoris (i.e. the non-specific training tasks). For the specific-training tasks, Cyclone did not enhance one-repetition maximum (1-RM) of lateral pull (p = 0.48) but there was a trend and large effect size for 1-RM of bench press (p = 0.07, d = 0.98) and 45° leg press (p = 0.07, d = 1.41). Cyclone resulted in an increase in number of repetitions for 80% pre-training 1-RM for lateral pull (p = 0.02, d = 1.30), bench press (p = 0.03, d = 1.20) with a trend for 45° leg press (p = 0.08, d = 0.96). Cyclone during resistance training enhanced the performance of 1-RM and number of repetitions at 80% of pre

  9. [New synthesis empathogenic agents].

    PubMed

    Velea, D; Hautefeuille, M; Vazeille, G; Lantran-Davoux, C

    1999-01-01

    The use of synthesis drugs is the object of numerous written articles and TV programs in the last, decade. These synthesis drugs or "designer drugs", are well known for their ability to enhance, reinforce or appease social difficulties and relationships. In the research for empathetic and entactogenic relations one discover an obvious lack of communication and "warmth" in personal or professional relationship. An image of chemical "well being" has become a frequent stereotype of a society with an atrophying of performance and values while supposedly dedicating itself to individual performance. The youths are the first victims of these new drugs, the economical and social environment are the main reinforcing factors of this behaviour. The main characteristic of these drugs, is the non-recognition of their danger, some users go so far as to describe this category of substances as "drugs which are not drugs". As a characteristic, the use of a these synthesis drugs is almost recreative, during the week-end and holiday. The drug addiction is different than that of opiates or cocaine. One can observe some cases of real dependence--corresponding to the DSW IV criterion--when the personality of the users is the main characteristic (narcissic failure, immature personality, family and school problems). Many adverse effects--hypertension, kidney failure, psychoses--were declared. The mass-media has presented many articles concerning Ecstasy (MDMA). This is the most used drug during the rave parties. Its adverse effects are well known and proven. The authors would like to present other more recent synthesis drugs, also known as "analogs". These drugs, a kind of mixture between amphetamine-like (MDMA, MBDB, MDA) and misused medicines (ketamine, gamma OH, atropine) represent a real danger. GHB, 2 CB, HMB, are some of these recent substances. The possibility to procure them on the Web, or to produce them by oneself, add to their danger because of the lack of controls on toxicity

  10. Metastatic Malignant Melanoma With Complete Loss of Differentiation Markers (Undifferentiated/Dedifferentiated Melanoma): Analysis of 14 Patients Emphasizing Phenotypic Plasticity and the Value of Molecular Testing as Surrogate Diagnostic Marker.

    PubMed

    Agaimy, Abbas; Specht, Katja; Stoehr, Robert; Lorey, Thomas; Märkl, Bruno; Niedobitek, Gerald; Straub, Melanie; Hager, Thomas; Reis, Anna-Carinna; Schilling, Bastian; Schneider-Stock, Regine; Hartmann, Arndt; Mentzel, Thomas

    2016-02-01

    Metastatic malignant melanoma is notorious for its phenotypic diversity and loss of differentiation markers. We herein summarized our experience with 14 metastatic melanomas showing complete loss of immunohistochemical melanocytic markers (with or without heterologous differentiation). Patients included 11 men and 3 women aged 24 to 78 years (median, 67 y). Thirteen patients had histologically confirmed primary skin melanoma, and 1 had metastatic melanoma of unknown primary. Undifferentiated metastasis was diagnosed synchronous to primary tumor (n=1), following skin melanoma by 3 months to 9 years (n=11) and preceding it by 1 year (n=1). Sites of undifferentiated metastases were axillary (3), inguinal (1), or submandibular (1) lymph nodes, digestive tract (2), bone/soft tissue (2), lung/pleura (2), and disseminated (n=3). Histology of metastases mimicked undifferentiated pleomorphic or spindle cell sarcoma with variable myxoid and giant cell areas (n=10) and cytokeratin-positive undifferentiated small cell sarcoma (n=1). Three cases showed heterologous dedifferentiation: pleomorphic rhabdomyosarcoma (n=1), teratocarcinosarcoma-like with prominent rhabdomyoblasts (n=1), and adenocarcinoma-like with metaplastic bone (n=1). All cases were negative for S100, melanoma cocktail, HMB45, Melan A, and SOX10. Other markers showed following results: smooth muscle actin (1/14), p16 (1/14), TP53 (2/12), pancytokeratin (4/14), desmin (5/14), h-caldesmon (0/9), and MDM2/CDK4 (0/5). SMARCB1 was intact in 8/8 cases. Genotyping showed BRAF(V600E) mutation (5/14), NRAS mutation (5/14), and BRAF/NRAS wild-type (4/14). In conclusion, undifferentiated/dedifferentiated metastatic melanoma is likely underrecognized and frequently mistaken for undifferentiated sarcoma or other neoplasms. Diagnosis of undifferentiated sarcoma at sites where melanoma metastasis are frequent (eg, inguinal and axillary region) should be made with great caution and warrants exploration of the remote history

  11. Expression of S-100 protein in renal cell neoplasms.

    PubMed

    Lin, Fan; Yang, Wannian; Betten, Mark; Teh, Bin Tean; Yang, Ximing J

    2006-04-01

    Polyclonal antibody to S-100 protein has been routinely applied for initial screening of various types of tumors, including, melanocytic tumors and neurogenic tumors. S-100 protein has been shown to have a broad distribution in human tissues, including renal tubules. The potential utility of S-100 protein in renal cell neoplasms has not been extensively investigated. Using an EnVision-Horseradish Peroxidase (HRP; Dako, Carpinteria, Calif) kit, we evaluated the diagnostic value of S-100 protein on tissue microarray sections from 175 cases of renal epithelial neoplasm (145 primary renal neoplasms and 30 metastatic renal cell carcinomas) and 24 non-neoplastic renal tissues. Immunohistochemical stains for pancytokeratin, HMB-45, and Mart-1 were also performed. Western blot using the same antibody (anti-S-100 protein) was performed on 10 cases of renal cell neoplasm. The results demonstrated that nuclear and cytoplasmic staining pattern for S-100 protein was observed in 56 (69%) of 81 conventional (clear cell) renal cell carcinomas (RCCs), 10 (30%) of 33 papillary RCCs, 1 (6%) of 16 ChRCCs, and 13 (87%) of 15 oncocytomas. Among the 81 cases of CRCC, positivity for S-100 protein was seen in 41 (71%) of 58 and 15 (65%) of 23 cases with Furhman nuclear grade I/II and III/IV, respectively. Focal immunostaining was present in 22 (92%) of 24 normal renal tubules. Similar staining pattern was observed in 21 (70%) of 30 metastatic RCCs. Western blotting demonstrated the S-100 protein expression in both renal cell neoplasm and normal renal tissue. Overexpression of S-100 in oncocytomas compared with ChRCCs was confirmed by the data of Western blot and cDNA microarray analysis. Importantly, 14.8% (12/81) of clear cell RCC and 13.3% (4/30) of metastatic RCC revealed an immunostaining profile of pancytokeratin (-)/S-100 protein (+). These data indicate that caution should be taken in interpreting an unknown primary with S-100 positivity and cytokeratin negativity. In addition, it

  12. AB046. The limitations in the diagnosis of mesenchymal neoplasms in bronchoscopy biopsy material—a case report

    PubMed Central

    Cheva, Angeliki; Kilmpasani, Maria; Karafoulidou, Ioanna; Pastelli, Nikoleta; Rampiadou, Christina; Tryfon, Stavros; Papaemmanouil, Styliani

    2016-01-01

    Background The case of a male patient, 68, who presented with one week’s history of cough, dyspnoe and hemosputum. Chest X-ray showed a shadow near the hilum of the right-sided lung. Furthtermore, CT scan of the thorax demonstrated a right middle lobe mass with signs of peripheral obstructive pneumonitis. Bronchoscopy revealed a stenosis of the right middle lobe, of which biopsy material was taken for microscopic examination. Methods The bioptic material consisted of seven pale-white tissue specimens, 0.2–0.3 cm in greatest diameter. Results The material contained blood clots, fibrin, and mucin, as well as superficial mucosal specimens. The submucosa of the latter was infiltrated by mainly medium-sized, neoplastic cells with crush artifacts and degenerative changes. These cells showed increased pleomorphy and atypia, with enlarged, abnormal nuclei and distinct nucleoli. Among the immunohistochemical stains, Vimentin, Desmin and Calponin were positively expressed, a fact that implies the mesenchymal origin of the neoplasm. On the other hand, SMA, Caldesmon, MyOD1, CD56, AE1/AE3, CK8/18, CK7, CK5/6, TTF-1, p63, CD45, HMB-45, S-100 and CD34 were negative. The proliferation marker (Ki67) was expressed in 80% of the neoplastic cells. Given the above findings, the diagnosis referred to a mesenchymal neoplasm (sarcoma) of myogenic origin, with high-grade malignancy. The patient received a platinum and taxane chemotherapy. Conclusions The microscopic examination of bronchoscopy biopsy material usually leads to the diagnosis of a variety of pulmonary diseases. Immunohistochemistry has significantly expanded the pathologist’s diagnostic abilities. However, in some cases, due to the rarity of the disease or the inappropriacy of the biopsy material, there can only be a rough estimation of the origin of the malignant neoplasm. In this case, the differential diagnosis would include, among else, a leiomyosarcoma, a synovial sarcoma, a fibrosarcoma, the spindle-cell variant

  13. ASASSN-17fp rebrightening event and ongoing monitoring

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2017-05-01

    ASASSN-17fp, discovered on 2017 April 28 and classified as a helium dwarf nova, was observed to be in outburst again on May 16 after fading 2.5 magnitudes from its original outburst. Dr. Tom Marsh (University of Warwick) and Dr. Elme Breedt (University of Cambridge) requested immediate time-series coverage. Dr. Breedt wrote: "The transient was identified as a helium dwarf nova (also known as an AMCVn star) from a spectrum taken by the PESSTO survey and reported in ATel #10334. Since then, we have been observing the target using the New Technology Telescope on La Silla in Chile. We measured a photometric period of 51 minutes in the first few nights during which the object was bright at g=16.03 (Marsh et al., ATel #10354), and then it faded to about g 18. However last night [ May 16] it brightened back to g 16 again, apparently starting a second outburst. Time series observations during this bright state would be very valuable to determine whether the 51 min period we saw in earlier data returns, and whether it is the orbital period of the binary or related to the distortion of the accretion disc in outburst (superhumps). If the 51 min signal is the orbital period or close to it, this would be the helium dwarf nova with the longest orbital period known. Multiple successive outbursts are not uncommon in binaries like this..." Observers should continue to monitor ASASSN-17fp with nightly snapshots for two weeks after it fades, in case it rebrightens again. It appears to have faded, according to an observation in the AAVSO International Database by F.-J. Hambsch (HMB, Mol, Belgium), who observed it remotely from Chile on 2017 May 24.2252 UT at magnitude 19.944 CV ± 0.595. Continue nightly snapshots through June 6 at least, and if it brightens again, resume time series. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (https://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Databa! se. See full Alert Notice

  14. Purification and characterization of α-Amylase from Miswak Salvadora persica

    PubMed Central

    2014-01-01

    Background The miswak (Salvadora persica) is a natural toothbrush. It is well known that very little information has been reported on enzymes in miswak as medicinal plant. Recently, we study peroxidase in miswak. In the present study, the main goal of this work is to purify and characterize α-amylase from miswak. The second goal is to study the storage stability of α-amylase in toothpaste. Method The purification method included chromatographaphy of miswak α-amylase on DEAE-Sepharose column and Sephacryl S-200 column. Molecular weight was determined by gel filtration and SDS-PAGE. Results Five α-amylases A1, A4a, A4b, A5a and A5b from miswak were purified and they had molecular weights of 14, 74, 16, 30 and 20 kDa, respectively. α-Amylases had optimum pH from 6 to 8. Affinity of the substrates toward all enzymes was studied. Miswak α-amylases A1, A4a, A4b, A5a and A5b had Km values for starch and glycogen of 3.7, 3.7, 7.1, 0.52, 4.3 mg/ml and 5.95, 5.9 4.16, 6.3, 6.49 mg/ml, respectively. The optimum temperature for five enzymes ranged 40°C- 60°C. Miswak α-amylases were stable up to 40°C- 60°C after incubation for 30 min. Ca+2 activated all the miswak α-amylases, while Ni2+, Co+2 and Zn+2 activated or inhibited some of these enzymes. The metal chelators, EDTA, sodium citrate and sodium oxalate had inhibitory effects on miswak α-amylases. PMSF, p-HMB, DTNB and 1,10 phenanthroline caused inhibitory effect on α-amylases. The analysis of hydrolytic products after starch hydrolysis by miswak α-amylases on paper chromatography revealed that glucose, maltose, maltotriose and oligosaccharide were the major products. Crude miswak α-amylase in the toothpaste retained 55% of its original activity after 10 months of storage at room temperature. Conclusions From these findings, α-amylases from miswak can be considered as beneficial enzymes for pharmaceuticals. Therefore, we study the storage stability of the crude α-amylase of miswak, which contained the five

  15. Inflammatory fibroid polyps of the gastrointestinal tract: evidence for a dendritic cell origin.

    PubMed

    Pantanowitz, Liron; Antonioli, Donald A; Pinkus, Geraldine S; Shahsafaei, Ali; Odze, Robert D

    2004-01-01

    Inflammatory fibroid polyps (IFPs) are rare mesenchymal tumors of the gastrointestinal tract that consist of spindle-shaped stromal cells and an inflammatory infiltrate rich in eosinophils. Their etiology and histogenesis remain unknown. Based on previous reports of their immunoreactivity for CD34 and c-kit biomarkers, IFPs have been thought to be related to gastrointestinal stromal tumors (GISTs). After reviewing the current literature and examining IFPs at the light microscopic level, we evaluated a series of IFPs using an extensive panel of immunohistochemical and in situ hybridization markers in an effort to gain insight into their etiology and histogenesis and to determine their true relationship to GISTs. Sixteen routinely processed IFP specimens (14 gastric, 1 ileal, and 1 rectal) were immunohistochemically stained for antibodies to CD34, HMB-45, desmin, smooth muscle actin, calponin, h-caldesmon, anaplastic lymphoma kinase, S-100 protein, epithelial membrane antigen, c-kit (CD117), stem cell factor (SCF/N19 or kit ligand), p53, bcl-2, cyclin D1, and human herpesvirus-8 (HHV8). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was also performed. Ten cases were further evaluated for the dendritic cell markers fascin, CD21, CD23, and CD35. Stromal cells were diffusely positive for CD34 and fascin in all (100%) cases, and these stromal cells were, in addition, immunoreactive for calponin and smooth muscle actin in 88% and 25% of cases, respectively. CD35 was also found to be focally reactive in the stromal cells. Cyclin-D1 was overexpressed in all (100%) IFPs. All other immunohistochemical markers and EBER were negative in the stromal cells. These findings suggest that the proliferating stromal cells in IFPs are of dendritic cell origin, with some cases also exhibiting myofibroblastic features. Absence of c-kit, SCF, and h-caldesmon immunoreactivity fails to support a relationship to GISTs. We also conclude that Epstein Barr virus and HHV8 are

  16. Xp11.2 translocation renal cell carcinoma with NONO-TFE3 gene fusion: morphology, prognosis, and potential pitfall in detecting TFE3 gene rearrangement.

    PubMed

    Xia, Qiu-Yuan; Wang, Zhe; Chen, Ni; Gan, Hua-Lei; Teng, Xiao-Dong; Shi, Shan-Shan; Wang, Xuan; Wei, Xue; Ye, Sheng-Bing; Li, Rui; Ma, Heng-Hui; Lu, Zhen-Feng; Zhou, Xiao-Jun; Rao, Qiu

    2017-03-01

    Xp11 translocation renal cell carcinomas are characterized by several different translocations involving the TFE3 gene. Tumors with different specific gene fusions may have different clinicopathological manifestations. Fewer than 10 renal cell carcinoma cases with NONO-TFE3 have been described. Here we examined eight additional cases of this rare tumor using clinicopathological, immunohistochemical, and molecular analyses. The male-to-female ratio of our study cohort was 1:1, and the median age was 30 years. The most distinctive feature of the tumors was that they exhibited glandular/tubular or papillary architecture that was lined with small-to-medium cuboidal to high columnar cells with indistinct cell borders and an abundantly clear or flocculent eosinophilic cytoplasm. The nuclei were oriented toward the luminal surface and were round and uniform in shape, which resulted in the appearance of secretory endometrioid subnuclear vacuolization. The distinct glandular/tubular or papillary architecture was often accompanied by sheets of epithelial cells that presented a biphasic pattern. Immunohistochemically, all eight cases demonstrated moderate (2+) or strong (3+) positive staining for TFE3, CD10, RCC marker, and PAX-8. None of the tumors were immunoreactive for CK7, Cathepsin K, Melan-A, HMB45, Ksp-cadherin, Vimentin, CA9, 34βE12 or CD117. NONO-TFE3 fusion transcripts were identified in six cases by RT-PCR. All eight cases showed equivocal split signals with a distance of nearly 2 signal diameters and sometimes had false-negative results. Furthermore, we developed a fluorescence in situ hybridization (FISH) assay to serve as an adjunct diagnostic tool for the detection of the NONO-TFE3 fusion gene and used this method to detect the fusion gene in all eight cases. Long-term follow-up (range, 10-102 months) was available for 7 patients. All 7 patients were alive with no evidence of recurrent disease or disease progression after their initial resection. This report

  17. Pleomorphic lymphoepithelioma-like carcinoma of the urinary bladder.

    PubMed

    Fadare, Oluwole; Renshaw, Idris L; Rubin, Christopher

    2009-01-01

    Lymphoepithelioma-like carcinoma (LELC) of the urinary bladder is often mixed with conventional transitional cell carcinoma and/or other histotypes. The pathologist's determination of the morphologic purity of a given LELC at the biopsy stage is a clinically relevant endeavour, because there is some anecdotal evidence suggesting that pure or predominant LELC may be comparatively chemosensitive and have a favorable prognostic profile, which may potentially offer the possibility of effective therapy without bladder resection. The precise degree of cellular pleomorphism that is allowed in a pure LELC is unclear. We describe herein an otherwise conventional and pure LELC that showed, in a localized area that constituted approximately 25% of the overall tumor volume, a two to six fold variation in nuclear size, including multinucleated tumor cells. These pleomorphic areas were set in the same lymphoplasmacytic infiltrate as their conventional counterparts, and similarly displayed cellular syncytia. We performed a detailed immunophenotypic comparison between the conventional areas and the pleomorphic areas. No significant differences were found between the 2 areas in overall lymphoplasmacytic or histiocytic density, lymphocytic CD4/CD8 ratio, and lymphoplasmacytic kappa/lambda ratio. Similarly, both displayed similar qualitative and quantitative staining indices for p53, Ki67, cytokeratin AE1/AE3 and p16(INKa). Scattered cells were cytoplasmically beta-catenin positive exclusively in the pleomorphic areas; however these cells were not notably larger than the cells in the conventional areas. Both components were immunohistochemically negative for HMB-45, CD1a, the estrogen receptor, Epstein-Barr virus, CD117, D2-40, CD56, cytokeratin 20 and chromogranin. Clinicopathologic analysis of a series of cases is required to establish if there is any significance to nuclear pleomorphism in LELC. However, the phenotypic similarity between the 2 areas in this case, the intimate

  18. A systematic review: perivascular epithelioid cell tumor of gastrointestinal tract

    PubMed Central

    Chen, Zehong; Han, Siqi; Wu, Jialin; Xiong, Minmin; Huang, Yanqiao; Chen, Jianhui; Yuan, Yujie; Peng, Jianjun; Song, Wu

    2016-01-01

    Abstract Perivascular epithelioid cell tumor (PEComa) is a rare entity with distinctive morphology and of expressing myomelanocytic markers. Gastrointestinal tract (GI) is one of the most common anatomic sites of origin and counts for 20% to 25% of all reported cases of perivascular epithelioid cell tumors not otherwise specified (PEComas-NOS). However, the biologic behavior of perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas-NOS) is still unclear. The aim of conducting this systematic review is to sum up what is known so far of the epidemiology, natural history, management and prognosis of GI PEComas-NOS. A systematic research was performed on PubMed and EMBASE using the following terms: (“perivascular epithelioid cell tumor” or “PEComa”) and (“gastrointestinal tract” or “GI” or “oral ” or “mouth” or “esophagus” or “gullet” or “gastric” or “stomach” or “duodenum” or “jejunum” or “ileum” or “cecum” or “colon” or “colorectal” or “sigmoid” or “rectum” or “anus” or “mesentery”) up to December 1, 2015. Retrieved GI PEComas-NOS publications, which included these terms, contains case reports, case series to case characteristic researches. A total of 168 articles were reviewed, 41 GI PEComa-NOS English studies among which were retrieved for analysis. We reviewed epidemiology, natural history, management and prognosis of GI PEComa-NOS. Generally GI PEComa-NOS is believed to have women predomination. The most frequently involved location is colon with non-specific clinical signs. Pathologically, GI PEComas-NOS shows epithelioid predominance (70%), meanwhile coexpresses melanocytic and muscle markers characteristically, while immunohistochemistry is a useful tool for identify, which indicates that HMB-45 is regarded as the most sensitive reagent. Complete resection served as mainstay of treatment, while chemotherapy should be unanimously considered to apply in malignant

  19. Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis

    SciTech Connect

    Lambros, Maria Polikandritou; Parsa, Cyrus; Mulamalla, HariChandana; Orlando, Robert; Lau, Bernard; Huang, Ying; Pon, Doreen; Chow, Moses

    2011-02-04

    Research highlights: {yields} We irradiated a 3-D human oral cell culture of keratinocytes and fibroblasts with 12 and 2 Gy. {yields} 6 h after irradiation the histopathology and apoptosis of the 3-D culture were evaluated. Microarrays were used to assess the gene expression in the irradiated 3-D tissue. {yields} 12 Gy induced significant histopathologic changes and cellular apoptosis. {yields} 12 Gy significantly affected genes of the NF-kB pathway, inflammatory cytokines and DAMPs. -- Abstract: Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this

  20. Comparative profiling of the transcriptional response to iron restriction in six serotypes of Actinobacillus pleuropneumoniae with different virulence potential

    PubMed Central

    2010-01-01

    Background Comparative analysis of gene expression among serotypes within a species can provide valuable information on important differences between related genomes. For the pig lung pathogen Actinobacillus pleuropneumoniae, 15 serotypes with a considerable variation in virulence potential and immunogenicity have been identified. This serotypic diversity can only partly be explained by amount of capsule and differences in the RTX toxin genes in their genomes. Iron acquisition in vivo is an important bacterial function and in pathogenic bacteria, iron-limitation is often a signal for the induction of virulence genes. We used a pan-genomic microarray to study the transcriptional response to iron restriction in vitro in six serotypes of A. pleuropneumoniae (1, 2, 3, 5b, 6, and 7), representing at least two levels of virulence. Results In total, 45 genes were significantly (p < 0.0001) up-regulated and 67 genes significantly down-regulated in response to iron limitation. Not previously observed in A. pleuropneumoniae was the up-regulation of a putative cirA-like siderophore in all six serotypes. Three genes, recently described in A. pleuropneumoniae as possibly coding for haemoglobin-haptoglobin binding proteins, displayed significant serotype related up-regulation to iron limitation. For all three genes, the expression appeared at its lowest in serotype 3, which is generally considered one of the least virulent serotypes of A. pleuropneumoniae. The three genes share homology with the hmbR haemoglobin receptor of Neisseria meningitidis, a possible virulence factor which contributes to bacterial survival in rats. Conclusions By comparative analysis of gene expression among 6 different serotypes of A. pleuropneumoniae we identified a common set of presumably essential core genes, involved in iron regulation. The results support and expand previous observations concerning the identification of new potential iron acquisition systems in A. pleuropneumoniae, showing that

  1. Purification and characterization of α-Amylase from Miswak Salvadora persica.

    PubMed

    Mohamed, Saleh A; Almulaiky, Yaaser Q; Ahmed, Youssri M; Al-Bar, Omar A M; Ibrahim, Ibrahim H

    2014-04-01

    The miswak (Salvadora persica) is a natural toothbrush. It is well known that very little information has been reported on enzymes in miswak as medicinal plant. Recently, we study peroxidase in miswak. In the present study, the main goal of this work is to purify and characterize α-amylase from miswak. The second goal is to study the storage stability of α-amylase in toothpaste. The purification method included chromatography of miswak α-amylase on DEAE-Sepharose column and Sephacryl S-200 column. Molecular weight was determined by gel filtration and SDS-PAGE. Five α-amylases A1, A4a, A4b, A5a and A5b from miswak were purified and they had molecular weights of 14, 74, 16, 30 and 20 kDa, respectively. α-Amylases had optimum pH from 6 to 8. Affinity of the substrates toward all enzymes was studied. Miswak α-amylases A1, A4a, A4b, A5a and A5b had Km values for starch and glycogen of 3.7, 3.7, 7.1, 0.52, 4.3 mg/ml and 5.95, 5.9 4.16, 6.3, 6.49 mg/ml, respectively. The optimum temperature for five enzymes ranged 40°C- 60°C. Miswak α-amylases were stable up to 40°C- 60°C after incubation for 30 min. Ca+2 activated all the miswak α-amylases, while Ni2+, Co+2 and Zn+2 activated or inhibited some of these enzymes. The metal chelators, EDTA, sodium citrate and sodium oxalate had inhibitory effects on miswak α-amylases. PMSF, p-HMB, DTNB and 1,10 phenanthroline caused inhibitory effect on α-amylases. The analysis of hydrolytic products after starch hydrolysis by miswak α-amylases on paper chromatography revealed that glucose, maltose, maltotriose and oligosaccharide were the major products. Crude miswak α-amylase in the toothpaste retained 55% of its original activity after 10 months of storage at room temperature. From these findings, α-amylases from miswak can be considered as beneficial enzymes for pharmaceuticals. Therefore, we study the storage stability of the crude α-amylase of miswak, which contained the five α-amylases, in toothpaste. The enzyme in

  2. Fractality in complex networks: critical and supercritical skeletons.

    PubMed

    Kim, J S; Goh, K-I; Salvi, G; Oh, E; Kahng, B; Kim, D

    2007-01-01

    connected to different boxes from a given box alpha as a function of the box mass M(B,alpha). It is obtained that the average perimeter over the boxes with box mass M(B) is likely to scale as <H(M(B))> approximately M(B), irrespective of the box size l(B).

  3. Morphological, immunohistochemical, and chromosomal analysis of multicystic chromophobe renal cell carcinoma, an architecturally unusual challenging variant.

    PubMed

    Foix, Maria Pané; Dunatov, Ana; Martinek, Petr; Mundó, Enric Condom; Suster, Saul; Sperga, Maris; Lopez, Jose I; Ulamec, Monika; Bulimbasic, Stela; Montiel, Delia Perez; Alaghehbandan, Reza; Peckova, Kvetoslava; Pivovarcikova, Krystina; Ondrej, Daum; Rotterova, Pavla; Skenderi, Faruk; Prochazkova, Kristyna; Dusek, Martin; Hora, Milan; Michal, Michal; Hes, Ondrej

    2016-12-01

    Chromophobe renal cell carcinoma (ChRCC) is typically composed of large leaf-like cells and smaller eosinophilic cells arranged in a solid-alveolar pattern. Eosinophilic, adenomatoid/pigmented, or neuroendocrine variants have also been described. We collected 10 cases of ChRCC with a distinct multicystic pattern out of 733 ChRCCs from our registry, and subsequently analyzed these by morphology, immunohistochemistry, and array comparative genomic hybridization. Of the 10 patients, 6 were males with an age range of 50-89 years (mean 68, median 69). Tumor size ranged between 1.2 and 20 cm (mean 5.32, median 3). Clinical follow-up was available for seven patients, ranging 1-19 years (mean 7.2, median 2.5). No aggressive behavior was documented. We observed two growth patterns, which were similar in all tumors: (1) variable-sized cysts, resembling multilocular cystic neoplasm of low malignant potential and (2) compressed cystic and tubular pattern with slit-like spaces. Raisinoid nuclei were consistently present while necrosis was absent in all cases. Half of the cases showed eosinophilic/oncocytic cytology, deposits of pigment (lipochrome) and microcalcifications. The other half was composed of pale or mixed cell populations. Immunostains for epithelial membrane antigen (EMA), CK7, OSCAR, CD117, parvalbumin, MIA, and Pax 8 were positive in all tumors while negative for vimentin, TFE3, CANH 9, HMB45, cathepsin K, and AMACR. Ki67 immunostain was positive in up to 1 % of neoplastic cells. Molecular genetic examination revealed multiple chromosomal losses in two fifths analyzable tumors, while three cases showed no chromosomal numerical aberrations. ChRCC are rarely arranged in a prominent multicystic pattern, which is probably an extreme form of the microcystic adenomatoid pigmented variant of ChRCC. The spectrum of tumors entering the differential diagnosis of ChRCC is quite different from that of conventional ChRCC. The immunophenotype of ChRCC is identical with

  4. PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity.

    PubMed

    Rao, Qiu; Shen, Qin; Xia, Qiu-yuan; Wang, Zi-yu; Liu, Biao; Shi, Shan-shan; Shi, Qun-li; Yin, Hong-lin; Wu, Bo; Ye, Sheng-bing; Li, Li; Chen, Jie-Yu; Pan, Min-hong; Li, Qing; Li, Rui; Wang, Xuan; Zhang, Ru-song; Yu, Bo; Ma, Heng-hui; Lu, Zhen-feng; Zhou, Xiao-jun

    2015-09-01

    An increasing number of TFE3 rearrangement-associated tumors, such as TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas), melanotic Xp11 translocation renal cancers, and melanotic Xp11 neoplasms, have recently been reported. We examined 12 such cases, including 5 TFE3 rearrangement-associated PEComas located in the pancreas, cervix, or pelvis and 7 melanotic Xp11 translocation renal cancers, using clinicopathologic, immunohistochemical, and molecular analyses. All the tumors shared a similar morphology, including a purely nested or sheet-like architecture separated by a delicate vascular network, purely epithelioid cells displaying a clear or granular eosinophilic cytoplasm, a lack of papillary structures and spindle cell or fat components, uniform round or oval nuclei containing small visible nucleoli, and, in most cases (11/12), melanin pigmentation. The levels of mitotic activity and necrosis varied. All 12 cases displayed moderately (2+) or strongly (3+) positive immunoreactivity for TFE3 and cathepsin K. One case labeled focally for HMB45 and Melan-A, whereas the others typically labeled moderately (2+) or strongly (3+) for 1 of these markers. None of the cases were immunoreactive for smooth muscle actin, desmin, CKpan, S100, or PAX8. PSF-TFE3 fusion genes were confirmed by reverse transcription polymerase chain reaction in cases (7/7) in which a novel PSF-TFE3 fusion point was identified. All of the cases displayed TFE3 rearrangement associated with Xp11 translocation. Furthermore, we developed a PSF-TFE3 fusion fluorescence in situ hybridization assay for the detection of the PSF-TFE3 fusion gene and detected it in all 12 cases. Clinical follow-up data were available for 7 patients. Three patients died, and 2 patients (cases 1 and 3) remained alive with no evidence of disease after initial resection. Case 2 experienced recurrence and remained alive with disease. Case 5, a recent case, remained alive with extensive abdominal cavity

  5. [Duration of Atrial Fibrillation Episodes and Implications for the Thromboembolic Risk].