Effects of illumination on human nocturnal serum melatonin levels and performance

NASA Technical Reports Server (NTRS)

Dollins, A. B.; Lynch, H. J.; Wurtman, R. J.; Deng, M. H.; Lieberman, H. R.

1993-01-01

In humans, exposure to bright light at night suppresses the normal nocturnal elevation in circulating melatonin. Oral administration of pharmacological doses of melatonin during the day, when melatonin levels are normally minimal, induces fatigue. To examine the relationship between illumination, human pineal function, and behavior, we monitored the overnight serum melatonin profiles and behavioral performance of 24 healthy male subjects. On each of three separate occasions subjects participated in 13.5 h (1630-0800 h) testing sessions. Each subject was assigned to an individually illuminated workstation that was maintained throughout the night at an illumination level of approximately 300, 1500, or 3000 lux. Melatonin levels were significantly diminished by light treatment, F(2, 36) = 12.77, p < 0.001, in a dose-dependent manner. Performance on vigilance, reaction time, and other tasks deteriorated throughout the night, consistent with known circadian variations in these parameters, but independent of ambient light intensity and circulating melatonin levels.

Pulse wave imaging in normal, hypertensive and aneurysmal human aortas in vivo: a feasibility study

NASA Astrophysics Data System (ADS)

Li, Ronny X.; Luo, Jianwen; Balaram, Sandhya K.; Chaudhry, Farooq A.; Shahmirzadi, Danial; Konofagou, Elisa E.

2013-07-01

Arterial stiffness is a well-established biomarker for cardiovascular risk, especially in the case of hypertension. The progressive stages of an abdominal aortic aneurysm (AAA) have also been associated with varying arterial stiffness. Pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique that uses the pulse wave-induced arterial wall motion to map the propagation of the pulse wave and measure the regional pulse wave velocity (PWV) as an index of arterial stiffness. In this study, the clinical feasibility of PWI was evaluated in normal, hypertensive, and aneurysmal human aortas. Radiofrequency-based speckle tracking was used to estimate the pulse wave-induced displacements in the abdominal aortic walls of normal (N = 15, mean age 32.5 ± 10.2 years), hypertensive (N = 13, mean age 60.8 ± 15.8 years), and aneurysmal (N = 5, mean age 71.6 ± 11.8 years) human subjects. Linear regression of the spatio-temporal variation of the displacement waveform in the anterior aortic wall over a single cardiac cycle yielded the slope as the PWV and the coefficient of determination r2 as an approximate measure of the pulse wave propagation uniformity. The aortic PWV measurements in all normal, hypertensive, and AAA subjects were 6.03 ± 1.68, 6.69 ± 2.80, and 10.54 ± 6.52 m s-1, respectively. There was no significant difference (p = 0.15) between the PWVs of the normal and hypertensive subjects while the PWVs of the AAA subjects were significantly higher (p < 0.001) compared to those of the other two groups. Also, the average r2 in the AAA subjects was significantly lower (p < 0.001) than that in the normal and hypertensive subjects. These preliminary results suggest that the regional PWV and the pulse wave propagation uniformity (r2) obtained using PWI, in addition to the PWI images and spatio-temporal maps that provide qualitative visualization of the pulse wave, may potentially provide valuable information for the clinical characterization of aneurysms and other vascular pathologies that regionally alter the arterial wall mechanics.

Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects-A Narrative Review of Human and Animal Evidence.

PubMed

Harvie, Michelle; Howell, Anthony

2017-01-19

Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month) studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation.

A Study of Dielectric Properties of Proteinuria between 0.2 GHz and 50 GHz

PubMed Central

Mun, Peck Shen; Ting, Hua Nong; Ong, Teng Aik; Wong, Chew Ming; Ng, Kwan Hong; Chong, Yip Boon

2015-01-01

This paper investigates the dielectric properties of urine in normal subjects and subjects with chronic kidney disease (CKD) at microwave frequency of between 0.2 GHz and 50 GHz. The measurements were conducted using an open-ended coaxial probe at room temperature (25°C), at 30°C and at human body temperature (37°C). There were statistically significant differences in the dielectric properties of the CKD subjects compared to those of the normal subjects. Statistically significant differences in dielectric properties were observed across the temperatures for normal subjects and CKD subjects. Pearson correlation test showed the significant correlation between proteinuria and dielectric properties. The experimental data closely matched the single-pole Debye model. The relaxation dispersion and relaxation time increased with the proteinuria level, while decreasing with the temperature. As for static conductivity, it increased with proteinuria level and temperature. PMID:26066351

Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication.

PubMed

Volkow, N D; Gillespie, H; Mullani, N; Tancredi, L; Grant, C; Valentine, A; Hollister, L

1996-05-31

Despite the widespread abuse of marijuana, knowledge about its effects in the human brain is limited. Brain glucose metabolism with and without delta 9 tetrahydrocannabinol (THC) (main psychoactive component of marijuana) was evaluated in eight normal subjects and eight chronic marijuana abusers with positron emission tomography. At baseline, marijuana abusers showed lower relative cerebellar metabolism than normal subjects. THC increased relative cerebellar metabolism in all subjects, but only abusers showed increases in orbitofrontal cortex, prefrontal cortex, and basal ganglia. Cerebellar metabolism during THC intoxication was significantly correlated with the subjective sense of intoxication. The decreased cerebellar metabolism in marijuana abusers at baseline could account for the motor deficits previously reported in these subjects. The activation of orbitofrontal cortex and basal ganglia by THC in the abusers but not in the normal subjects could underlie one of the mechanisms leading to the drive and the compulsion to self-administer the drug observed in addicted individuals.

The 3-Second Rule in Hereditary Pure Cerebellar Ataxia: A Synchronized Tapping Study

PubMed Central

Matsuda, Shunichi; Matsumoto, Hideyuki; Furubayashi, Toshiaki; Hanajima, Ritsuko; Tsuji, Shoji; Ugawa, Yoshikazu; Terao, Yasuo

2015-01-01

The ‘3-second rule’ has been proposed based on miscellaneous observations that a time period of around 3 seconds constitutes the fundamental unit of time related to the neuro-cognitive machinery in normal humans. The aim of paper was to investigate the temporal processing in patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration, using a synchronized tapping task. Seventeen SCA patients (11 SCA6, 6 SCA31) and 17 normal age-matched volunteers participated. The task required subjects to tap a keyboard in synchrony with sequences of auditory stimuli presented at fixed interstimulus intervals (ISIs) between 200 and 4800 ms. In this task, the subjects required non-motor components to estimate the time of forthcoming tone in addition to motor components to tap. Normal subjects synchronized their taps to the presented tones at shorter ISIs, whereas as the ISI became longer, the normal subjects displayed greater latency between the tone and the tapping (transition zone). After the transition zone, normal subjects pressed the button delayed relative to the tone. On the other hand, SCA patients could not synchronize their tapping with the tone even at shorter ISIs, although they pressed the button delayed relative to the tone earlier than normal subjects did. The earliest time of delayed tapping appearance after the transition zone was 4800 ms in normal subjects but 1800 ms in SCA patients. The span of temporal integration in SCA patients is shortened compared to that in normal subjects. This could represent non-motor cerebellar dysfunction in SCA patients. PMID:25706752

A link between FTO, ghrelin, and impaired brain food-cue responsivity

PubMed Central

Karra, Efthimia; O’Daly, Owen G.; Choudhury, Agharul I.; Yousseif, Ahmed; Millership, Steven; Neary, Marianne T.; Scott, William R.; Chandarana, Keval; Manning, Sean; Hess, Martin E.; Iwakura, Hiroshi; Akamizu, Takashi; Millet, Queensta; Gelegen, Cigdem; Drew, Megan E.; Rahman, Sofia; Emmanuel, Julian J.; Williams, Steven C.R.; Rüther, Ulrich U.; Brüning, Jens C.; Withers, Dominic J.; Zelaya, Fernando O.; Batterham, Rachel L.

2013-01-01

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO “obesity-risk” rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans. PMID:23867619

A link between FTO, ghrelin, and impaired brain food-cue responsivity.

PubMed

Karra, Efthimia; O'Daly, Owen G; Choudhury, Agharul I; Yousseif, Ahmed; Millership, Steven; Neary, Marianne T; Scott, William R; Chandarana, Keval; Manning, Sean; Hess, Martin E; Iwakura, Hiroshi; Akamizu, Takashi; Millet, Queensta; Gelegen, Cigdem; Drew, Megan E; Rahman, Sofia; Emmanuel, Julian J; Williams, Steven C R; Rüther, Ulrich U; Brüning, Jens C; Withers, Dominic J; Zelaya, Fernando O; Batterham, Rachel L

2013-08-01

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans.

General anesthesia suppresses normal heart rate variability in humans

NASA Astrophysics Data System (ADS)

Matchett, Gerald; Wood, Philip

2014-06-01

The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

Estimating the concentration of urea and creatinine in the human serum of normal and dialysis patients through Raman spectroscopy.

PubMed

de Almeida, Maurício Liberal; Saatkamp, Cassiano Junior; Fernandes, Adriana Barrinha; Pinheiro, Antonio Luiz Barbosa; Silveira, Landulfo

2016-09-01

Urea and creatinine are commonly used as biomarkers of renal function. Abnormal concentrations of these biomarkers are indicative of pathological processes such as renal failure. This study aimed to develop a model based on Raman spectroscopy to estimate the concentration values of urea and creatinine in human serum. Blood sera from 55 clinically normal subjects and 47 patients with chronic kidney disease undergoing dialysis were collected, and concentrations of urea and creatinine were determined by spectrophotometric methods. A Raman spectrum was obtained with a high-resolution dispersive Raman spectrometer (830 nm). A spectral model was developed based on partial least squares (PLS), where the concentrations of urea and creatinine were correlated with the Raman features. Principal components analysis (PCA) was used to discriminate dialysis patients from normal subjects. The PLS model showed r = 0.97 and r = 0.93 for urea and creatinine, respectively. The root mean square errors of cross-validation (RMSECV) for the model were 17.6 and 1.94 mg/dL, respectively. PCA showed high discrimination between dialysis and normality (95 % accuracy). The Raman technique was able to determine the concentrations with low error and to discriminate dialysis from normal subjects, consistent with a rapid and low-cost test.

The potentiation by caffeine of X-ray damage to cultured human skin fibroblasts from normal subjects and ataxia-telangiectasia patients

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

Furcinitti, P.S.

1983-07-01

Caffeine was found to potentiate X-ray-induced killing of human diploid fibroblasts from a normal subject and an ataxia-telangiectasia (AT) patient when it was present at 2 mM concentration for 30 to 66 hr postirradiation. The dose-modifying factor for caffeine-treated normal cells had an average value of 1.26 +/- 0.13 which did not vary significantly with treatment time or X-ray dose. The dose-modifying factor for caffeine-treated AT cells was 1.12 +/- 0.12 at 30 hr, rose to 1.66 +/- 0.17 at 41 hr, and decreased to 1.31 +/- 0.13 at 66 hr. Thus no clear difference was observed between these twomore » cell strains' susceptibility to postirradiation caffeine treatment.« less

Potentiation by caffeine of x-ray damage to cultured human skin fibroblasts from normal subjects and ataxia-telangiectasia patients

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

Furcinitti, P.S.

1983-07-01

Caffeine was found to potentiate x-ray-induced killing of human diploid fibroblasts from a normal subject and an ataxia-telangiectasia (AT) patient when it was present at 2 mM concentration for 30 to 66 h postirradiation. The dose-modifying factor for caffeine-treated normal cells had an average value of 1.26 +- 0.13 which did not vary significantly with treatment time or x-ray dose. The dose-modifying factor for caffeine-treated AT cells was 1.12 +- 0.12 at 30 h, rose to 1.66 +- 0.17 at 41 h, and decreased to 1.31 +- 0.13 at 66 h. Thus no clear difference was observed between these twomore » cell strains' susceptibility to postirradiation caffeine treatment.« less

Canonical Wnt Signaling as a Specific Mark of Normal and Tumorigenic Mammary Stem Cells

DTIC Science & Technology

2011-02-01

aggressive mammary tumors. 15. SUBJECT TERMS Breast cancer stem cells, Wnt signaling, canonical Wnt signaling, B-catenin, normal stem cells, adult stem...Wnt pathway is associated with abnormal mouse mammary development, tumorigenesis, and human breast cancer. In addition, increasing evidence suggests...activation occurs in human breast cancer and is required for proliferation of various other stem cell compartments, addressing how Wnt signaling promotes

Correlation of Respirator Fit Measured on Human Subjects and a Static Advanced Headform

PubMed Central

Bergman, Michael S.; He, Xinjian; Joseph, Michael E.; Zhuang, Ziqing; Heimbuch, Brian K.; Shaffer, Ronald E.; Choe, Melanie; Wander, Joseph D.

2015-01-01

This study assessed the correlation of N95 filtering face-piece respirator (FFR) fit between a Static Advanced Headform (StAH) and 10 human test subjects. Quantitative fit evaluations were performed on test subjects who made three visits to the laboratory. On each visit, one fit evaluation was performed on eight different FFRs of various model/size variations. Additionally, subject breathing patterns were recorded. Each fit evaluation comprised three two-minute exercises: “Normal Breathing,” “Deep Breathing,” and again “Normal Breathing.” The overall test fit factors (FF) for human tests were recorded. The same respirator samples were later mounted on the StAH and the overall test manikin fit factors (MFF) were assessed utilizing the recorded human breathing patterns. Linear regression was performed on the mean log10-transformed FF and MFF values to assess the relationship between the values obtained from humans and the StAH. This is the first study to report a positive correlation of respirator fit between a headform and test subjects. The linear regression by respirator resulted in R2 = 0.95, indicating a strong linear correlation between FF and MFF. For all respirators the geometric mean (GM) FF values were consistently higher than those of the GM MFF. For 50% of respirators, GM FF and GM MFF values were significantly different between humans and the StAH. For data grouped by subject/respirator combinations, the linear regression resulted in R2 = 0.49. A weaker correlation (R2 = 0.11) was found using only data paired by subject/respirator combination where both the test subject and StAH had passed a real-time leak check before performing the fit evaluation. For six respirators, the difference in passing rates between the StAH and humans was < 20%, while two respirators showed a difference of 29% and 43%. For data by test subject, GM FF and GM MFF values were significantly different for 40% of the subjects. Overall, the advanced headform system has potential for assessing fit for some N95 FFR model/sizes. PMID:25265037

Radioimmunoassay of Human Serum Thyrotrophin

PubMed Central

Hall, Reginald; Amos, Jacqueline; Ormston, Brian J.

1971-01-01

The double antibody radioimmunoassay of serum thyroid-stimulating hormone (TSH) allows measurement of circulating levels of the hormone in most normal subjects. The serum TSH level in normal subjects is 1·6 ± 0·8μU/ml. Patients with non-toxic goitre and acromegaly have normal TSH levels. Values are always raised in hypothyroid patients (with primary thyroid disease) and are significantly lowered in those with hyperthyroidism. Of the many stimuli used in an attempt to raise TSH levels in normal adult subjects only three—synthetic thyrotrophin-releasing hormone, ethinyloestradiol, and carbimazole plus iodides—have been effective. The major clinical application of the TSH immunoassay lies in the diagnosis of minor degrees of hypothyroidism. An impaired response of serum TSH to synthetic thyrotrophin-releasing hormone should also help in the diagnosis of hypopituitarism affecting TSH production. PMID:5548300

Localization and molecular forms of galanin in human adrenals: elevated levels in pheochromocytomas.

PubMed

Bauer, F E; Hacker, G W; Terenghi, G; Adrian, T E; Polak, J M; Bloom, S R

1986-12-01

Galanin immunoreactivity was measured by RIA, using antibodies directed against both the non-C- and C-terminal positions of porcine galanin, in tissue extracts of normal adrenals and pheochromocytomas and also in the plasma of normal subjects and patients with pheochromocytomas. No C-terminal galanin-like immunoreactivity was detected in plasma or tissue, suggesting differences in the amino acid sequence of human compared with porcine galanin. A non-C-terminally directed antibody was, therefore, used to characterize human galanin immunoreactivity by gel permeation chromatography and reverse phase high pressure liquid chromatography and to localize it by immunocytochemistry. The galanin content of whole adrenal gland was 2.6 +/- 0.9 (+/- SEM) pmol/g (n = 5). In contrast, however, pheochromocytomas had much greater concentrations (21 +/- 2.3 pmol/g; n = 16). Gel chromatography and reverse phase high pressure liquid chromatography revealed 2 molecular forms of galanin immunoreactivity with identical elution positions in both normal adrenals and tumors. The concentration of galanin in plasma from both normal subjects and pheochromocytoma patients was below the detection limit of the assay (less than 10 pmol/liter). Using immunocytochemistry, galanin was localized to scattered cells or clusters of tumor cells in 5 of 11 pheochromocytomas and only a few chromaffin cells and cortical nerve fibers in normal adrenals.

Age-related changes in human posture control: Motor coordination tests

NASA Technical Reports Server (NTRS)

Peterka, R. J.; Black, F. O.

1989-01-01

Postural responses to support surface displacements were measured in 214 normal human subjects ranging in age from 7 to 81 years. Motor tests measured leg muscle Electromyography (EMG) latencies, body sway, and the amplitude and timing of changes in center of pressure displacements in response to sudden forward and backward horizontal translations of the support surface upon which the subjects stood. There were small increases in both EMG latencies and the time to reach the peak amplitude of center of pressure responses with increasing age. The amplitude of center of pressure responses showed little change with age if the amplitude measures were normalized by a factor related to subject height. In general, postural responses to sudden translations showed minimal changes with age, and all age related trends which were identified were small relative to the variability within the population.

Predicting variability of aquatic concentrations of human pharmaceuticals

EPA Science Inventory

Potential exposure to active pharmaceutical ingredients (APIs) in the aquatic environment is a subject of ongoing concern. We recently estimated maximum likely potency-normalized exposure rates at the national level for several hundred commonly used human prescription pharmaceut...

Native fluorescence characterization of human liver abnormalities

NASA Astrophysics Data System (ADS)

Ganesan, Singaravelu; Madhuri, S.; Aruna, Prakasa R.; Suchitra, S.; Srinivasan, T. G.

1999-05-01

Fluorescence spectroscopy of intrinsic biomolecules has been extensively used in biology and medicine for the past several decades. In the present study, we report the native fluorescence characteristics of blood plasma from normal human subjects and patients with different liver abnormalities such as hepatitis, leptospirosis, jaundice, cirrhosis and liver cell failure. Native fluorescence spectra of blood plasma -- acetone extract were measured at 405 nm excitation. The average spectrum of normal blood plasma has a prominent emission peak around 464 nm whereas in the case of liver diseased subjects, the primary peak is red shifted with respect to normal. In addition, liver diseased cases show distinct secondary emission peak around 615 nm, which may be attributed to the presence of endogenous porphyrins. The red shift of the prominent emission peak with respect to normal is found to be maximum for hepatitis and minimum for cirrhosis whereas the secondary emission peak around 615 nm was found to be more prominent in the case of cirrhosis than the rest. The ratio parameter I465/I615 is found to be statistically significant (p less than 0.001) in discriminating liver abnormalities from normal.

The Role of Standardized and Study-specific Human Brain Diffusion Tensor Templates in Inter-subject Spatial Normalization

PubMed Central

Zhang, Shengwei; Arfanakis, Konstantinos

2012-01-01

Purpose To investigate the effect of standardized and study-specific human brain diffusion tensor templates on the accuracy of spatial normalization, without ignoring the important roles of data quality and registration algorithm effectiveness. Materials and Methods Two groups of diffusion tensor imaging (DTI) datasets, with and without visible artifacts, were normalized to two standardized diffusion tensor templates (IIT2, ICBM81) as well as study-specific templates, using three registration approaches. The accuracy of inter-subject spatial normalization was compared across templates, using the most effective registration technique for each template and group of data. Results It was demonstrated that, for DTI data with visible artifacts, the study-specific template resulted in significantly higher spatial normalization accuracy than standardized templates. However, for data without visible artifacts, the study-specific template and the standardized template of higher quality (IIT2) resulted in similar normalization accuracy. Conclusion For DTI data with visible artifacts, a carefully constructed study-specific template may achieve higher normalization accuracy than that of standardized templates. However, as DTI data quality improves, a high-quality standardized template may be more advantageous than a study-specific template, since in addition to high normalization accuracy, it provides a standard reference across studies, as well as automated localization/segmentation when accompanied by anatomical labels. PMID:23034880

Normalizing and scaling of data to derive human response corridors from impact tests.

PubMed

Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A

2014-06-03

It is well known that variability is inherent in any biological experiment. Human cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine responses to impact loading for crashworthiness applications including civilian (motor vehicle) and military environments. It is important to transform measured variables from PMHS tests (accelerations, forces and deflections) to a standard or reference population, termed normalization. The transformation process should account for inter-specimen variations with some underlying assumptions used during normalization. Scaling is a process by which normalized responses are converted from one standard to another (example, mid-size adult male to large-male and small-size female adults, and to pediatric populations). These responses are used to derive corridors to assess the biofidelity of anthropomorphic test devices (crash dummies) used to predict injury in impact environments and design injury mitigating devices. This survey examines the pros and cons of different approaches for obtaining normalized and scaled responses and corridors used in biomechanical studies for over four decades. Specifically, the equal-stress equal-velocity and impulse-momentum methods along with their variations are discussed in this review. Methods ranging from subjective to quasi-static loading to different approaches are discussed for deriving temporal mean and plus minus one standard deviation human corridors of time-varying fundamental responses and cross variables (e.g., force-deflection). The survey offers some insights into the potential efficacy of these approaches with examples from recent impact tests and concludes with recommendations for future studies. The importance of considering various parameters during the experimental design of human impact tests is stressed. Published by Elsevier Ltd.

Regional Myocardial Blood Flow*

PubMed Central

Sullivan, Jay M.; Taylor, Warren J.; Elliott, William C.; Gorlin, Richard

1967-01-01

A method is described which measures the local effectiveness of the myocardial circulation, expressed as a clearance constant. Uniform clearance constants have been demonstrated in the normal canine and human myocardium. A distinct difference in clearance constants has been demonstrated between the normal canine myocardium and areas of naturally occurring disease. Heterogeneous clearance constants have been found in a majority of human subjects with coronary artery disease—the lowest rates being noted in areas of fibrous aneurysm. PMID:6036537

Biomechanical measurements of stopping and stripping torques during screw insertion in five types of human and artificial humeri.

PubMed

Aziz, Mina Sr; Tsuji, Matthew Rs; Nicayenzi, Bruce; Crookshank, Meghan C; Bougherara, Habiba; Schemitsch, Emil H; Zdero, Radovan

2014-05-01

During orthopedic surgery, screws are inserted by "subjective feel" in humeri for fracture fixation, that is, stopping torque, while trying to prevent accidental over-tightening that causes screw-bone interface failure, that is, stripping torque. However, no studies exist on stopping torque, stripping torque, or stopping/stripping torque ratio in human or artificial humeri. This study evaluated five types of humeri, namely, human fresh-frozen (n = 19), human embalmed (n = 18), human dried (n = 15), artificial "normal" (n = 13), and artificial "osteoporotic" (n = 13). An orthopedic surgeon used a torque screwdriver to insert 3.5-mm-diameter cortical screws into humeral shafts and 6.5-mm-diameter cancellous screws into humeral heads by "subjective feel" to obtain stopping and stripping torques. The five outcome measures were raw and normalized stopping torque, raw and normalized stripping torque, and stopping/stripping torque ratio. Normalization was done as raw torque/screw-bone interface area. For "gold standard" fresh-frozen humeri, cortical screw tests yielded averages of 1312 N mm (raw stopping torque), 30.4 N/mm (normalized stopping torque), 1721 N mm (raw stripping torque), 39.0 N/mm (normalized stripping torque), and 82% (stopping/stripping torque ratio). Similarly, fresh-frozen humeri gave cancellous screw average results of 307 N mm (raw stopping torque), 0.9 N/mm (normalized stopping torque), 392 N mm (raw stripping torque), 1.2 N/mm (normalized stripping torque), and 79% (stopping/stripping torque ratio). Of the five cortical screw parameters for fresh-frozen humeri versus other groups, statistical equivalence (p ≥ 0.05) occurred in four cases (embalmed), three cases (dried), four cases (artificial "normal"), and four cases (artificial "osteoporotic"). Of the five cancellous screw parameters for fresh-frozen humeri versus other groups, statistical equivalence (p ≥ 0.05) occurred in five cases (embalmed), one case (dried), one case (artificial "normal"), and zero cases (artificial "osteoporotic"). Stopping/stripping torque ratios were relatively constant for all groups at 77%-88% (cortical screws) and 79%-92% (cancellous screws). © IMechE 2014.

Microbiomes of the normal middle ear and ears with chronic otitis media.

PubMed

Minami, Shujiro B; Mutai, Hideki; Suzuki, Tomoko; Horii, Arata; Oishi, Naoki; Wasano, Koichiro; Katsura, Motoyasu; Tanaka, Fujinobu; Takiguchi, Tetsuya; Fujii, Masato; Kaga, Kimitaka

2017-10-01

The aim of this study was to profile and compare the middle ear microbiomes of human subjects with and without chronic otitis media. Prospective multicenter cohort study. All consecutive patients undergoing tympanoplasty surgery for chronic otitis media or ear surgery for conditions other than otitis media were recruited. Sterile swab samples were collected from the middle ear mucosa during surgery. The variable region 4 of the 16S rRNA gene in each sample were amplified using region-specific primers adapted for the Illumina MiSeq sequencer (Illumina, CA, USA)). The sequences were subjected to local blast and classified using Metagenome@KIN (World Fusion, Tokyo, Japan). In total, 155 participants were recruited from seven medical centers. Of these, 88 and 67 had chronic otitis media and normal middle ears, respectively. The most abundant bacterial phyla on the mucosal surfaces of the normal middle ears were Proteobacteria, followed by Actinobacteria, Firmicutes, and Bacteroidetes. The children and adults with normal middle ears differed significantly in terms of middle ear microbiomes. Subjects with chronic otitis media without active inflammation (dry ear) had similar middle ear microbiomes as the normal middle ears group. Subjects with chronic otitis media with active inflammation (wet ear) had a lower prevalence of Proteobacteria and a higher prevalence of Firmicutes than the normal middle ears. The human middle ear is inhabited by more diverse microbial communities than was previously thought. Alteration of the middle ear microbiome may contribute to the pathogenesis of chronic otitis media with active inflammation. 2b. Laryngoscope, 127:E371-E377, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence

PubMed Central

Harvie, Michelle; Howell, Anthony

2017-01-01

Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month) studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation. PMID:28106818

Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects.

PubMed

Le Prell, Colleen G; Dell, Shawna; Hensley, Brittany; Hall, James W; Campbell, Kathleen C M; Antonelli, Patrick J; Green, Glenn E; Miller, James M; Guire, Kenneth

2012-01-01

One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.

A Four-Dimensional Probabilistic Atlas of the Human Brain

PubMed Central

Mazziotta, John; Toga, Arthur; Evans, Alan; Fox, Peter; Lancaster, Jack; Zilles, Karl; Woods, Roger; Paus, Tomas; Simpson, Gregory; Pike, Bruce; Holmes, Colin; Collins, Louis; Thompson, Paul; MacDonald, David; Iacoboni, Marco; Schormann, Thorsten; Amunts, Katrin; Palomero-Gallagher, Nicola; Geyer, Stefan; Parsons, Larry; Narr, Katherine; Kabani, Noor; Le Goualher, Georges; Feidler, Jordan; Smith, Kenneth; Boomsma, Dorret; Pol, Hilleke Hulshoff; Cannon, Tyrone; Kawashima, Ryuta; Mazoyer, Bernard

2001-01-01

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype– phenotype–behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders. PMID:11522763

Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis

PubMed Central

Nakatsuji, Teruaki; Chen, Tiffany H.; Narala, Saisindhu; Chun, Kimberly A.; Two, Aimee M.; Yun, Tong; Shafiq, Faiza; Kotol, Paul F.; Bouslimani, Amina; Melnik, Alexey V.; Latif, Haythem; Kim, Ji-Nu; Lockhart, Alexandre; Artis, Keli; David, Gloria; Taylor, Patricia; Streib, Joanne; Dorrestein, Pieter C.; Grier, Alex; Gill, Steven R.; Zengler, Karsten; Hata, Tissa R.; Leung, Donald Y. M.; Gallo, Richard L.

2017-01-01

The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S.aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S.aureus. The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis. These AMPs were strain-specific, highly potent, selectively killed S.aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S.aureus. These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease. PMID:28228596

Protein Microarray Analysis in Patients With Asthma*

PubMed Central

Kim, Hyo-Bin; Kim, Chang-Keun; Iijima, Koji; Kobayashi, Takao; Kita, Hirohito

2010-01-01

Background Microarray technology offers a new opportunity to gain insight into global gene and protein expression profiles in asthma. To identify novel factors produced in the asthmatic airway, we analyzed sputum samples by using a membrane-based human cytokine microarray technology in patients with bronchial asthma (BA). Methods Induced sputum was obtained from 28 BA subjects, 20 nonasthmatic atopic control (AC) subjects, and 38 nonasthmatic nonatopic normal control (NC) subjects. The microarray samples of subjects were randomly selected from nine BA subjects, three AC subjects, and six NC subjects. Sputum supernatants were analyzed using a custom human cytokine array (RayBio Custom Human Cytokine Array; RayBiotech; Norcross, GA) designed to analyze 79 specific cytokines simultaneously. The levels of growth-regulated oncogene (GRO)-α, eotaxin-2, and pulmonary and activation-regulated chemokine (PARC)/CCL18 were measured by sandwich enzyme-linked immunosorbent assays (ELISAs), and eosinophil-derived neurotoxin (EDN) was measured by radioimmunoassay. Results By microarray, the signal intensities for GRO-α, eotaxin-2, and PARC were significantly higher in BA subjects than in AC and NC subjects (p = 0.036, p = 0.042, and p = 0.033, respectively). By ELISA, the sputum PARC protein levels were significantly higher in BA subjects than in AC and NC subjects (p < 0.0001). Furthermore, PARC levels correlated significantly with sputum eosinophil percentages (r = 0.570, p < 0.0001) and the levels of EDN(r = 0.633, p < 0.0001), the regulated upon activation, normal T cell expressed and secreted cytokine (r = 0.440, p < 0.001), interleukin-4 (r = 0.415, p < 0.01), and interferon-γ (r = 0.491, p < 0.001). Conclusions By a nonbiased screening approach, a chemokine, PARC, is elevated in sputum specimens from patients with asthma. PARC may play important roles in development of airway eosinophilic inflammation in asthma. PMID:19017877

I Vivo Characterization of Ultrasonic Backscattering from Normal and Abnormal Lungs.

NASA Astrophysics Data System (ADS)

Jafari, Farhad

The primary goal of this project has been to characterize the lung tissue in its in vivo ultrasonic backscattering properties in normal human subjects, and study the changes in the lung echo characteristics under various pathological conditions. Such a characterization procedure is used to estimate the potential of ultrasound for providing useful diagnostic information about the superficial region of the lung. The results of this study may be divided into three categories: (1) This work has resulted in the ultrasonic characterization of lung tissue, in vivo, and has investigated the various statistical features of the lung echo properties in normal human subjects. The echo properties of the lungs are characterized with respect to the mean echo amplitude relative to a perfect reflector and the mean autocorrelation of normalized echo signals. (2) A theoretical model is developed to simulate the ultrasonic backscattering properties of the lung under normal and various simulated abnormal conditions. This model has been tested on various phantoms simulating the strong acoustic interactions of the lung. When applied to the lung this model has shown excellent agreement to experimental data gathered on a population of normal human subjects. By varying a few of the model parameters, the effect of changes in the lung structural parameters on the detected ultrasonic echoes is investigated. It is found that alveoli size changes of about 50 percent and concentration changes of 40 percent may produce spectral changes exceeding the variability exhibited by normal lungs. (3) Ultrasonic echoes from the lungs of 4 groups of patients were studied. The groups included patients with edema, emphysema, pneumothorax, and patients undergoing radiation therapy for treatment of lung cancer. Significant deviations from normal lung echo characteristics is observed in more than 80 percent of the patients studied. These deviations are intercompared and some qualitative associations between the echo characteristics on each patient group and their pulmonary pathology is made. It is concluded that the technique may provide a potential tool in detecting pulmonary abnormalities. More controlled patient studies, however, are indicated as necessary to determine the sensitivity of the ultrasound technique.

Multi-frequency time-difference complex conductivity imaging of canine and human lungs using the KHU Mark1 EIT system.

PubMed

Kuen, Jihyeon; Woo, Eung Je; Seo, Jin Keun

2009-06-01

We evaluated the performance of the lately developed electrical impedance tomography (EIT) system KHU Mark1 through time-difference imaging experiments of canine and human lungs. We derived a multi-frequency time-difference EIT (mftdEIT) image reconstruction algorithm based on the concept of the equivalent homogeneous complex conductivity. Imaging experiments were carried out at three different frequencies of 10, 50 and 100 kHz with three different postures of right lateral, sitting (or prone) and left lateral positions. For three normal canine subjects, we controlled the ventilation using a ventilator at three tidal volumes of 100, 150 and 200 ml. Three human subjects were asked to breath spontaneously at a normal tidal volume. Real- and imaginary-part images of the canine and human lungs were reconstructed at three frequencies and three postures. Images showed different stages of breathing cycles and we could interpret them based on the understanding of the proposed mftdEIT image reconstruction algorithm. Time series of images were further analyzed by using the functional EIT (fEIT) method. Images of human subjects showed the gravity effect on air distribution in two lungs. In the canine subjects, the morphological change seems to dominate the gravity effect. We could also observe that two different types of ventilation should have affected the results. The KHU Mark1 EIT system is expected to provide reliable mftdEIT images of the human lungs. In terms of the image reconstruction algorithm, it would be worthwhile including the effects of three-dimensional current flows inside the human thorax. We suggest clinical trials of the KHU Mark1 for pulmonary applications.

Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

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

Romshe, C.A.; Zipf, W.B.; Miser, A.

1984-02-01

We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significantmore » differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.« less

Effects of vasopressin administration on diuresis of water immersion in normal humans

NASA Technical Reports Server (NTRS)

Epstein, M.; Denunzio, A. G.; Loutzenhiser, R. D.

1981-01-01

The influence of vasopressin suppression on the diuresis encountered during water immersion is investigated in studies on normal humans immersed to the neck. Six hydrated male subjects were studied on two occasions while undergoing 6 h of immersion without or during the administration of aqueous vasopressin for the initial 4 h. Neck immersion is found to result in a significant increase in urinary flow rate beginning in the first hour and persisting throughout the immersion. The administration of vasopressin markedly attenuated the diuretic response throughout the period of infusion, while cessation of vasopressin administration during the final 2 h of immersion resulted in a marked offset of the antidiuresis. Results thus support the view that the suppression of antidiuretic hormone contributes to the immersion diuresis of hydrated subjects.

Otolith and Vertical Canal Contributions to Dynamic Postural Control

NASA Technical Reports Server (NTRS)

Black, F. Owen

1999-01-01

The objective of this project is to determine: 1) how do normal subjects adjust postural movements in response to changing or altered otolith input, for example, due to aging? and 2) how do patients adapt postural control after altered unilateral or bilateral vestibular sensory inputs such as ablative inner ear surgery or ototoxicity, respectively? The following hypotheses are under investigation: 1) selective alteration of otolith input or abnormalities of otolith receptor function will result in distinctive spatial, frequency, and temporal patterns of head movements and body postural sway dynamics. 2) subjects with reduced, altered, or absent vertical semicircular canal receptor sensitivity but normal otolith receptor function or vice versa, should show predictable alterations of body and head movement strategies essential for the control of postural sway and movement. The effect of altered postural movement control upon compensation and/or adaptation will be determined. These experiments provide data for the development of computational models of postural control in normals, vestibular deficient subjects and normal humans exposed to unusual force environments, including orbital space flight.

The dependence of binocular contrast sensitivities on binocular single vision in normal and amblyopic human subjects

PubMed Central

Hood, A S; Morrison, J D

2002-01-01

We have measured monocular and binocular contrast sensitivities in response to medium to high spatial frequencies of vertical sinusoidal grating patterns in normal subjects, anisometropic amblyopes, strabismic amblyopes and non-amblyopic esotropes. On binocular viewing, contrast sensitivities were slightly but significantly increased in normal subjects, markedly increased in anisometropes and esotropes with anomalous binocular single vision (BSV) and significantly reduced in esotropes and exotropes without BSV. Application of a prismatic correction to the strabismic eye in order to achieve bifoveal stimulation resulted in a significant reduction in contrast sensitivity in esotropes with and without anomalous BSV, in exotropes and in non-amblyopic esotropes. Control experiments in normal subjects with monocular viewing showed that degradative effects of the prism occurred only with high prism powers and at high spatial frequencies, thus establishing that the reduced contrast sensitivities were the consequence of bifoveal stimulation rather than optical degradation. Displacement of the image of the grating pattern by 2 deg in normal subjects and anisometropes by a dichoptic method to simulate a small angle esotropia had no effect on the contrast sensitivities recorded through the companion eye. By contrast, esotropes showed similar reductions in contrast sensitivity to those obtained with the prism experiments, confirming a fundamental difference between subjects with normal and abnormal ocular alignments. The results have thus established a suppressive action of the fovea of the amblyopic eye acting on the companion, non-amblyopic eye and indicate that correction of ocular misalignments in adult esotropes may be disadvantageous to binocular visual performance. PMID:11956347

Upper-normal waist circumference is a risk marker for metabolic syndrome in normal-weight subjects.

PubMed

Okada, R; Yasuda, Y; Tsushita, K; Wakai, K; Hamajima, N; Matsuo, S

2016-01-01

To elucidate implication of upper-normal waist circumference (WC), we examined whether the normal range of WC still represents a risk of metabolic syndrome (MetS) or non-adipose MetS components among normal-weight subjects. A total of 173,510 persons (100,386 men and 73,124 women) with normal WC (<90/80 cm in men/women) and body mass index (BMI) of 18.5-24.9 were included. Subjects were categorized as having low, moderate, and upper-normal WC for those with WC < 80, 80-84, and 85-89 cm in men and <70, 70-74, and 75-79 cm in women, respectively. The prevalence of all the non-adipose MetS components (e.g. prediabetes and borderline dyslipidemia) was significantly higher in subjects with upper-normal WC on comparison with those with low WC. Overall, the prevalence of MetS (having three or more of four non-adipose MetS components) gradually increased with increasing WC (12%, 21%, and 27% in men and 11%, 14%, and 19% in women for low, moderate, and upper-normal WC, respectively). Moreover, the risk of having a greater number of MetS components increased in subjects with upper-normal WC compared with those with low WC (odds ratios for the number of one, two, three, and four MetS components: 1.29, 1.81, 2.53, and 2.47 in men and 1.16, 1.55, 1.49, and 2.20 in women, respectively). Upper-normal WC represents a risk for acquiring a greater number of MetS components and the early stage of MetS components (prediabetes and borderline dyslipidemia), after adjusting for BMI, in a large general population with normal WC and BMI. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Comparisons of auditory brainstem response and sound level tolerance in tinnitus ears and non-tinnitus ears in unilateral tinnitus patients with normal audiograms

PubMed Central

An, Yong-Hwi; Kim, Dong Hyun; Yoon, Ji Eun; Yoon, Ji Hyang

2017-01-01

Objective Recently, “hidden hearing loss” with cochlear synaptopathy has been suggested as a potential pathophysiology of tinnitus in individuals with a normal hearing threshold. Several studies have demonstrated that subjects with tinnitus and normal audiograms show significantly reduced auditory brainstem response (ABR) wave I amplitudes compared with control subjects, but normal wave V amplitudes, suggesting increased central auditory gain. We aimed to reconfirm the “hidden hearing loss” theory through a within-subject comparison of wave I and wave V amplitudes and uncomfortable loudness level (UCL), which might be decreased with increased central gain, in tinnitus ears (TEs) and non-tinnitus ears (NTEs). Subjects and methods Human subjects included 43 unilateral tinnitus patients (19 males, 24 females) with normal and symmetric hearing thresholds and 18 control subjects with normal audiograms. The amplitudes of wave I and V from the peak to the following trough were measured twice at 90 dB nHL and we separately assessed UCLs at 500 Hz and 3000 Hz pure tones in each TE and NTE. Results The within-subject comparison between TEs and NTEs showed no significant differences in wave I and wave V amplitude, or wave V/I ratio in both the male and female groups. Individual data revealed increased V/I amplitude ratios > mean + 2 SD in 3 TEs, but not in any control ears. We found no significant differences in UCL at 500 Hz or 3000 Hz between the TEs and NTEs, but the UCLs of both TEs and NTEs were lower than those of the control ears. Conclusions Our ABR data do not represent meaningful evidence supporting the hypothesis of cochlear synaptopathy with increased central gain in tinnitus subjects with normal audiograms. However, reduced sound level tolerance in both TEs and NTEs might reflect increased central gain consequent on hidden synaptopathy that was subsequently balanced between the ears by lateral olivocochlear efferents. PMID:29253030

Regulation of the oncodevelopmental expression of type 1 chain ABH and Lewis(b) blood group antigens in human colon by alpha-2-L-fucosylation.

PubMed Central

Orntoft, T F; Greenwell, P; Clausen, H; Watkins, W M

1991-01-01

Blood group antigen expression in the distal human colon is related to the development of the organ and is modified by malignant transformation. To elucidate the biochemical basis for these changes, we have (a) analysed the activity of glycosyltransferases coded for by the H, Se, Le, X, and A genes, in tissue biopsy specimens from normal and malignant proximal and distal human colon; (b) characterised the glycosphingolipids expressed in the various regions of normal and malignant colon by immunostaining of high performance thin layer chromatography plates; and (c) located the antigens on tissue sections from the same subjects by immunohistochemistry. In both secretors and non-secretors we found a significantly higher activity of alpha-2-L-fucosyltransferases in carcinomatous rectal tissue than in tissue from normal subjects, whereas the other transferase activities studied showed no significant differences. The acceptor substrate specificity suggested that both the Se and the H gene dependent alpha-2-L-fucosyltransferases are increased in carcinomas. In non-malignant tissue the only enzyme which showed appreciably higher activity in caecum than in rectum was alpha-2-L-fucosyltransferase. Immunochemistry and immunohistochemistry showed alpha-2-L-fucosylated structures in normal caecum from secretors and in tumour tissue from both secretors and non-secretors. We conclude that the alpha-2-L-fucosyltransferases control the expression of ABH, and Lewis(b) structures in normal and malignant colon. Images Figure 4 PMID:1826491

Plasma Shh levels reduced in pancreatic cancer patients

PubMed Central

El-Zaatari, Mohamad; Daignault, Stephanie; Tessier, Art; Kelsey, Gail; Travnikar, Lisa A.; Cantu, Esperanza F.; Lee, Jamie; Plonka, Caitlyn M.; Simeone, Diane M.; Anderson, Michelle A.; Merchant, Juanita L.

2012-01-01

Objectives Normally, sonic hedgehog (Shh) is expressed in the pancreas during fetal development and transiently after tissue injury. Although pancreatic cancers express Shh, it is not known if the protein is secreted into the blood and whether its plasma levels change with pancreatic transformation. The goal of this study was to develop an ELISA to detect human Shh in blood, and determine the levels in subjects with and without pancreatic cancer. Methods A human Shh ELISA assay was developed, and plasma Shh levels were measured in blood samples from normal volunteers and subjects with pancreatitis or pancreatic cancer. The biological activity of plasma Shh was tested using NIH-3T3 cells. Results The average levels of Shh in human blood were lower in pancreatitis and pancreatic cancer patients than in normal individuals. Hematopoietic cells did not express Shh suggesting that Shh is secreted into the bloodstream. Plasma fractions enriched for Shh did not induce Gli-1 mRNA suggesting that the protein was not biologically active. Conclusions Shh is secreted from tissues and organs into the circulation but its activity is blocked by plasma proteins. Reduced plasma levels were found in pancreatic cancer patients, but alone were not sufficient to predict pancreatic cancer. PMID:22513293

Digital music exposure reliably induces temporary threshold shift (TTS) in normal hearing human subjects

PubMed Central

Le Prell, C. G.; Dell, S.; Hensley, B.; Hall, J. W.; Campbell, K. C. M.; Antonelli, P. J.; Green, G. E.; Miller, J. M.; Guire, K.

2012-01-01

Objectives One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is availability of an established clinical paradigm with real world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal hearing human subjects. Design Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93–95 (n=10), 98–100 (n=11), or 100–102 (n=12) dBA in-ear exposure level for a period of four hours. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured prior to and after music exposure. Post-music tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and one week later. Results Changes in thresholds after the lowest level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a “notch” configuration, with the largest changes observed at 4 kHz (mean=6.3±3.9dB; range=0–13 dB). Recovery was largely complete within the first 4 hours post-exposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1-week post-exposure. Conclusions These data provide insight into the variability of TTS induced by music player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function following digital music player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values. PMID:22885407

CRALBP is a highly prevalent autoantigen for human autoimmune uveitis.

PubMed

Deeg, Cornelia A; Raith, Albert J; Amann, Barbara; Crabb, John W; Thurau, Stephan R; Hauck, Stefanie M; Ueffing, Marius; Wildner, Gerhild; Stangassinger, Manfred

2007-01-01

Cellular retinaldehyde binding protein (CRALBP) is an autoantigen in spontaneous equine recurrent uveitis. In order to test whether CRALBP contributes to human autoimmune uveitis, the specificity of antibodies from human uveitis patient's sera was first evaluated in two-dimensional (2D) Western blot analysis. Subsequent identification of the immunoreactive proteins by mass spectrometry resulted in the identification of CRALBP as a putative autoantigen. Additionally, sera from human uveitis and control patients were by Western blot using purified human recombinant CRALBP. Anti-CRALBP autoantibodies occur more frequently (P<.01) in human uveitis patients than in normal controls. Thirty out of 56 tested uveitis patient's sera contained autoantibodies reactive against CRALBP, compared to only four out of 23 normal control subjects. The presence of CRALBP autoantibodies in 54% of tested uveitis patients supports CRALBP as a possible autoantigen in human autoimmune uveitis.

Relation of dietary salt and aldosterone to urinary protein excretion in subjects with resistant hypertension.

PubMed

Pimenta, Eduardo; Gaddam, Krishna K; Pratt-Ubunama, Monique N; Nishizaka, Mari K; Aban, Inmaculada; Oparil, Suzanne; Calhoun, David A

2008-02-01

Experimental data indicate that the cardiorenal effects of aldosterone excess are dependent on concomitant high dietary salt intake. Such an interaction of endogenous aldosterone and dietary salt has not been observed previously in humans. We assessed the hypothesis that excess aldosterone and high dietary sodium intake combine to worsen proteinuria in patients with resistant hypertension. Consecutive subjects with resistant hypertension (n=84) were prospectively evaluated by measurement of 24-hour urinary aldosterone (Ualdo), sodium, and protein (Uprot) excretion. Subjects were analyzed according to aldosterone status (high: Ualdo >or=12 microg/24 hours; or normal: <12 microg/24 hours) and dietary salt intake based on tertiles of urinary sodium. The mean clinic blood pressure for all of the subjects was 161.4+/-22.4/89.8+/-13.5 mm Hg on an average of 4.3 medications. There was no blood pressure difference between study groups. Uprot was significantly higher in the 38 subjects with high Ualdo compared with the 46 subjects with normal Ualdo (143.0+/-83.8 versus 95.9+/-81.7 mg/24 hours; P=0.01). Among subjects with high Ualdo, Uprot increased progressively across urinary sodium groups (P<0.05). In contrast, there was no difference in Uprot across sodium tertiles among subjects with normal Ualdo. A positive correlation between Uprot and urinary sodium (r=0.47; P=0.003) was observed in subjects with high Ualdo but not in subjects with normal Ualdo (r=0.18; P value not significant). These results suggest that aldosterone excess and high dietary salt combine to increase urinary protein excretion.

Sour Ageusia in Two Individuals Implicates Ion Channels of the ASIC and PKD Families in Human Sour Taste Perception at the Anterior Tongue

PubMed Central

Huque, Taufiqul; Cowart, Beverly J.; Dankulich-Nagrudny, Luba; Pribitkin, Edmund A.; Bayley, Douglas L.; Spielman, Andrew I.; Feldman, Roy S.; Mackler, Scott A.; Brand, Joseph G.

2009-01-01

Background The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli. Methods and Findings Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1β, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-β2, the δ-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as β-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1β, PKD2L1, phospholipase C-β2, and δ-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells. Conclusions These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals (“natural knockouts”) suggests a cell lineage for sour that is independent of the other taste modalities. PMID:19812697

SHILAJIT: EVALUTION OF ITS EFFECTS ON BLOOD CHEMISTRY OF NORMAL HUMAN SUBJECTS

PubMed Central

Sharma, Praveen; Jha, Jagrati; Shrinivas, V.; Dwivedi, L.K.; Suresh, P.; Sinha, M.

2003-01-01

The effect of Shilajit on blood chemistry was studied in normal human volunteers. Administration of two gms of Shilajit for 45 days did not produced any significant change in physical parameters i.e. blood pressure, pulse rate and body weight and similarly no charge was observed in hematological parameters. A signification reduction in Serum Triglycerides, Serum cholesterol with simultaneous improvement in HDL Cholesterol was seen, besides Shilajit also improved antioxidant status of volunteers. Results of study suggest hypolipidemic and strong antioxidant activity of Shilajit. PMID:22557121

Shilajit: evalution of its effects on blood chemistry of normal human subjects.

PubMed

Sharma, Praveen; Jha, Jagrati; Shrinivas, V; Dwivedi, L K; Suresh, P; Sinha, M

2003-10-01

The effect of Shilajit on blood chemistry was studied in normal human volunteers. Administration of two gms of Shilajit for 45 days did not produced any significant change in physical parameters i.e. blood pressure, pulse rate and body weight and similarly no charge was observed in hematological parameters. A signification reduction in Serum Triglycerides, Serum cholesterol with simultaneous improvement in HDL Cholesterol was seen, besides Shilajit also improved antioxidant status of volunteers. Results of study suggest hypolipidemic and strong antioxidant activity of Shilajit.

Comparison of smooth pursuit and combined eye-head tracking in human subjects with deficient labyrinthine function

NASA Technical Reports Server (NTRS)

Leigh, R. J.; Thurston, S. E.; Sharpe, J. A.; Ranalli, P. J.; Hamid, M. A.

1987-01-01

The effects of deficient labyrinthine function on smooth visual tracking with the eyes and head were investigated, using ten patients with bilateral peripheral vestibular disease and ten normal controls. Active, combined eye-head tracking (EHT) was significantly better in patients than smooth pursuit with the eyes alone, whereas normal subjects pursued equally well in both cases. Compensatory eye movements during active head rotation in darkness were always less in patients than in normal subjects. These data were used to examine current hypotheses that postulate central cancellation of the vestibulo-ocular reflex (VOR) during EHT. A model that proposes summation of an integral smooth pursuit command and VOR/compensatory eye movements is consistent with the findings. Observation of passive EHT (visual fixation of a head-fixed target during en bloc rotation) appears to indicate that in this mode parametric gain changes contribute to modulation of the VOR.

Quantitative analysis of peripheral blood Th0, Th1, Th2 and the Th1:Th2 cell ratio during normal human pregnancy and preeclampsia

PubMed Central

Saito, S; Sakai, M; Sasaki, Y; Tanebe, K; Tsuda, H; Michimata, T

1999-01-01

We calculated the percentage of Th1, Th2, Th0 cells and the Th1:Th2 cell ratio of peripheral blood from normal pregnant subjects and preeclampsia patients using flow cytometry which can analyse both the surface marker, CD4, and intracellular cytokines, interleukin (IL)-4 and interferon (IFN)-γ. In normal pregnancy, the percentage of Th1 cells was significantly lower in the third trimester, and the ratios of Th1:Th2 were significantly lower in the second and third trimester than in nonpregnant subjects. In contrast, the percentage of Th1 cells and the ratios of Th1:Th2 in preeclampsia were significantly higher than in normal third trimester pregnant subjects. The percentage of Th2 cells in preeclampsia was significantly lower than in third trimester of normal pregnancy. Additionally, peripheral blood mononuclear cells from these subjects and patients were cultured with phytohemagglutinin stimulation, and IL-4 and IFN-γ concentrations were determined in the supernatant by enzymed linked immunosorbent assays. The percentage of Th1 and Th2, and the ratios of Th1:Th2 were correlated with cytokine (IFN-γ and IL-4) secretion level. These results demonstrated that Th2 cells were predominant in the second and third trimesters of normal pregnancy, but Th1 cells predominated in preeclamptic patients. PMID:10469061

Short-Term Plasticity of the Visuomotor Map during Grasping Movements in Humans

ERIC Educational Resources Information Center

Safstrom, Daniel; Edin, Benoni B.

2005-01-01

During visually guided grasping movements, visual information is transformed into motor commands. This transformation is known as the "visuomotor map." To investigate limitations in the short-term plasticity of the visuomotor map in normal humans, we studied the maximum grip aperture (MGA) during the reaching phase while subjects grasped objects…

Cardiovascular and respiratory physiopathological aspects of hypokinesia

NASA Technical Reports Server (NTRS)

Dagianti, A.

1980-01-01

The many effects of hypokinesia on the human organism are described. The differences in normally mobile subjects and hypokinetic subjects as relates to heart rate, average humeral pressure, cardiac capacity, cardia index, systolic range, and large cycle resistances are discussed. It is concluded that further studies must be carried out in seven specific areas of cariocirculatory damage due to hypokinesia.

EEG topography and tomography (LORETA) in the classification and evaluation of the pharmacodynamics of psychotropic drugs.

PubMed

Saletu, Bernd; Anderer, Peter; Saletu-Zyhlarz, Gerda M

2006-04-01

By multi-lead computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (QEEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping or topography), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ, the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects and therapeutic efficacy will be discussed. Imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be shown for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently. By considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. Thus, pharmaco-EEG topography and tomography are valuable methods in human neuropsychopharmacology, clinical psychiatry and neurology.

Mapping the human genome

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

Annas, G.C.; Elias, S.

1992-01-01

This article is a review of the book Mapping the Human Genome: Using Law and Ethics as Guides, edited by George C. Annas and Sherman Elias. The book is a collection of essays on the subject of using ethics and laws as guides to justify human gene mapping. It addresses specific issues such problems related to eugenics, patents, insurance as well as broad issues such as the societal definitions of normality.

Microtubule Abnormalities Underlying Gulf War Illness in Neurons from Human-Induced Pluripotent Cells

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-15-1-0433 TITLE: Microtubule Abnormalities Underlying Gulf War Illness in Neurons from Human -Induced Pluripotent Cells...2015 - 31 Aug 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Microtubule Abnormalities Underlying Gulf War Illness in Neurons from Human -Induced...functions to normal in neurons derived from human pluripotent cells exposed to Gulf War toxins. 15. SUBJECT TERMS microtubule, neuron, Gulf War Illness

Discussion of Source Reconstruction Models Using 3D MCG Data

NASA Astrophysics Data System (ADS)

Melis, Massimo De; Uchikawa, Yoshinori

In this study we performed the source reconstruction of magnetocardiographic signals generated by the human heart activity to localize the site of origin of the heart activation. The localizations were performed in a four compartment model of the human volume conductor. The analyses were conducted on normal subjects and on a subject affected by the Wolff-Parkinson-White syndrome. Different models of the source activation were used to evaluate whether a general model of the current source can be applied in the study of the cardiac inverse problem. The data analyses were repeated using normal and vector component data of the MCG. The results show that a distributed source model has the better accuracy in performing the source reconstructions, and that 3D MCG data allow finding smaller differences between the different source models.

Distribution and release of human pancreatic polypeptide.

PubMed

Adrian, T E; Bloom, S R; Bryant, M G; Polak, J M; Heitz, P H; Barnes, A J

1976-12-01

A simple and reliable radioimmunoassay has been developed for a new gut hormone, HPP. In the primate 93% of the total PP was found in the pancreas with a small amount throughout the remaining gastrointestinal tract. HPP has been shown to be produced by a number of pancreatic apudomas and their metastases. The immunoreactive PP from these tumours and from normal pancreas was chromatographically indistinguishable from the pure peptide. The plasma PP concentration rose rapidly after a meal in normal subjects and was still raised six hours later. Fasting plasma PP levels in patients with PP cell containing pancreatic endocrine tumours were higher than even the postprandial level in normal subjects. PP measurements is thus useful in diagnosis of pancreatic endocrine tumours.

Distribution and release of human pancreatic polypeptide.

PubMed Central

Adrian, T E; Bloom, S R; Bryant, M G; Polak, J M; Heitz, P H; Barnes, A J

1976-01-01

A simple and reliable radioimmunoassay has been developed for a new gut hormone, HPP. In the primate 93% of the total PP was found in the pancreas with a small amount throughout the remaining gastrointestinal tract. HPP has been shown to be produced by a number of pancreatic apudomas and their metastases. The immunoreactive PP from these tumours and from normal pancreas was chromatographically indistinguishable from the pure peptide. The plasma PP concentration rose rapidly after a meal in normal subjects and was still raised six hours later. Fasting plasma PP levels in patients with PP cell containing pancreatic endocrine tumours were higher than even the postprandial level in normal subjects. PP measurements is thus useful in diagnosis of pancreatic endocrine tumours. Images Fig. 2 PMID:828120

Comparisons of auditory brainstem response and sound level tolerance in tinnitus ears and non-tinnitus ears in unilateral tinnitus patients with normal audiograms.

PubMed

Shim, Hyun Joon; An, Yong-Hwi; Kim, Dong Hyun; Yoon, Ji Eun; Yoon, Ji Hyang

2017-01-01

Recently, "hidden hearing loss" with cochlear synaptopathy has been suggested as a potential pathophysiology of tinnitus in individuals with a normal hearing threshold. Several studies have demonstrated that subjects with tinnitus and normal audiograms show significantly reduced auditory brainstem response (ABR) wave I amplitudes compared with control subjects, but normal wave V amplitudes, suggesting increased central auditory gain. We aimed to reconfirm the "hidden hearing loss" theory through a within-subject comparison of wave I and wave V amplitudes and uncomfortable loudness level (UCL), which might be decreased with increased central gain, in tinnitus ears (TEs) and non-tinnitus ears (NTEs). Human subjects included 43 unilateral tinnitus patients (19 males, 24 females) with normal and symmetric hearing thresholds and 18 control subjects with normal audiograms. The amplitudes of wave I and V from the peak to the following trough were measured twice at 90 dB nHL and we separately assessed UCLs at 500 Hz and 3000 Hz pure tones in each TE and NTE. The within-subject comparison between TEs and NTEs showed no significant differences in wave I and wave V amplitude, or wave V/I ratio in both the male and female groups. Individual data revealed increased V/I amplitude ratios > mean + 2 SD in 3 TEs, but not in any control ears. We found no significant differences in UCL at 500 Hz or 3000 Hz between the TEs and NTEs, but the UCLs of both TEs and NTEs were lower than those of the control ears. Our ABR data do not represent meaningful evidence supporting the hypothesis of cochlear synaptopathy with increased central gain in tinnitus subjects with normal audiograms. However, reduced sound level tolerance in both TEs and NTEs might reflect increased central gain consequent on hidden synaptopathy that was subsequently balanced between the ears by lateral olivocochlear efferents.

Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias

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

Muta, K.; Nishimura, J.; Ideguchi, H.

1987-06-01

To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: number of binding sites; affinity; and recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of /sup 125/I-transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects. Among those with an aplastic anemia, hemolytic anemia, myelodysplastic syndrome, and polycythemia veramore » compared to normal subjects, there were no considerable differences in the numbers of binding sites. The dissociation constants (Kd) were measured using Scatchard analysis. The apparent Kd was unchanged (about 10 nmol/L) in patients and normal subjects. The kinetics of endocytosis and exocytosis of /sup 125/I-transferrin, examined by acid treatment, revealed no variations in recycling kinetics among the patients and normal subjects. These data suggest that iron uptake is regulated by modulation of the number of surface transferrin receptors, thereby reflecting the iron demand of the erythroblast.« less

Mucin-type O-glycans in Tears of Normal Subjects and Patients with Non-Sjögren’s Dry Eye

PubMed Central

Guzman-Aranguez, Ana; Mantelli, Flavio; Argüeso, Pablo

2009-01-01

Purpose O-linked carbohydrates (O-glycans) contribute to the hydrophilic character of mucins in mucosal tissues. This study aimed to identify the repertoire of O-glycans in the tear film, and the glycosyltransferases associated with their biosynthesis, in normal subjects and patients with non-Sjögren’s dry eye. Methods Human tear fluid was collected from the inferior conjunctival fornix. O-glycans were released by hydrazinolysis, labeled with 2-aminobenzamide, and analyzed by fluorometric, high-performance liquid chromatography (HPLC) coupled with exoglycosidase digestions. O-glycan structures identified in tears were related to potential biosynthetic pathways in human conjunctival epithelium using a glycogene microarray database. Lectin-binding analyses were performed using agglutinins from Arachis hypogaea, Maackia amurensis, and Sambucus nigra. Results The O-glycan profile of human tears consisted primarily of core 1 (Galβ1-3GalNAcα1-Ser/Thr)-based structures. Mono-sialyl O-glycans represented approximately 66% of the glycan pool, being α2-6-sialyl core 1 the predominant O-glycan structure in human tears (48%). Four families of glycosyltranferases potentially related to the biosynthesis of these structures were identified in human conjunctiva. These included thirteen polypeptide-GalNAc-transferases (GALNT), the core 1 β-3-galactosyltransferase (T-synthase), three α2-6-sialyltransferases (ST6GalNAc), and two α2-3-sialyltransferases (ST3Gal). No significant differences in total amount of O-glycans were detected between tears of normal subjects and dry eye patients, by HPLC and lectin blot. Likewise, no differences in glycosyltransferase expression were found by glycogene microarray. Conclusions This study identifies the most common mucin-type O-glycans in human tears and their expected biosynthetic pathways in ocular surface epithelia. Patients with non-Sjögren’s dry eye show no alterations in composition and amount of O-glycans in the tear fluid. PMID:19407012

Glucagon-like peptide-1 receptor expression on human eosinophils and its regulation of eosinophil activation.

PubMed

Mitchell, P D; Salter, B M; Oliveria, J P; El-Gammal, A; Tworek, D; Smith, S G; Sehmi, R; Gauvreau, G M; Butler, M; O'Byrne, P M

2017-03-01

Glucagon-like peptide-1 (GLP-1) and its receptor are part of the incretin family of hormones that regulate glucose metabolism. GLP-1 also has immune modulatory roles. To measure the expression of the GLP-1 receptor (GLP-1R) on eosinophils and neutrophils in normal and asthmatic subjects and evaluate effects of a GLP-1 analog on eosinophil function. Peripheral blood samples were taken from 10 normal and 10 allergic asthmatic subjects. GLP-1R expression was measured on eosinophils and neutrophils. Subsequently, the asthmatic subjects underwent allergen and diluent inhalation challenges, and GLP-1R expression was measured. Purified eosinophils, collected from mild asthmatic subjects, were stimulated with lipopolysaccharide (LPS) and a GLP-1 analog to evaluate eosinophil cell activation markers CD11b and CD69 and cytokine (IL-4, IL-5, IL-8 and IL-13) production. Glucagon-like peptide-1 receptor is expressed on human eosinophils and neutrophils. Eosinophil, but not neutrophil, expression of GLP-1R is significantly higher in normal controls compared to allergic asthmatics. The expression of GLP-1R did not change on either eosinophils or neutrophils following allergen challenge. A GLP-1 analog significantly decreased the expression of eosinophil-surface activation markers following LPS stimulation and decreased eosinophil production of IL-4, IL-8 and IL-13, but not IL-5. Glucagon-like peptide-1 receptor is expressed on human eosinophils and neutrophils. A GLP-1 analog attenuates LPS-stimulated eosinophil activation. GLP-1 agonists may have additional adjunctive indications in treating persons with concomitant type 2 diabetes mellitus and asthma. © 2016 John Wiley & Sons Ltd.

Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: Evidence for further genetic heterogeneity in this syndrome

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

Brown, T.R.; Lubahn, D.B.; Wilson, E.M.

1988-11-01

The cloning of a cDNA for the human androgen receptor gene has resulted in the availability for cDNA probes that span various parts of the gene, including the entire steroid-binding domain and part of the DNA-binding domain, as well as part of the 5' region of the gene. The radiolabeled probes were used to screen for androgen receptor mutations on Southern blots prepared by restriction endonuclease digestion of genomic DNA from human subjects with complete androgen insensitivity syndrome (AIS). In this investigation, the authors considered only patients presenting complete AIS and with the androgen receptor (-) form as the mostmore » probably subjects to show a gene deletion. One subject from each of six unrelated families with the receptor (-) form of complete AIS and 10 normal subjects were studied. In the 10 normal subjects and in 5 of the 6 patients, identical DNA restriction fragment patterns were observed with EcoRI and BamHI. Analysis of other members of this family confirmed the apparent gene deletion. The data provide direct proof that complete AIS in some families can result from a deletion of the androgen receptor structural gene. However, other families do not demonstrate such a deletion, suggesting that point mutations may also result in the receptor (-) form of complete AIS, adding further to the genetic heterogeneity of this syndrome.« less

An ultrastructural study of the effect of neomycin on the colon in the human subject and in the conventional and the germ-free mouse.

PubMed

Aluwihare, A P

1971-05-01

An electron microscopic study of the colon of normal mice and human subjects and those treated with neomycin is reported; there is a close resemblance between the mouse and human colons. After rapid disinfection of the colon, there is epithelial cell damage due to a toxic effect of the drug, a reduction in epithelial turnover accompanying the change in flora, and an important reduction in the cellularity of the lamina propria mainly due to a reduction in inflammatory cells. The changes in the lamina propria probably represent changes in the antipathogenetic defences of the host.

Compass: clinical evaluation of a new instrument for the diagnosis of glaucoma.

PubMed

Rossetti, Luca; Digiuni, Maurizio; Rosso, Alberto; Riva, Roberta; Barbaro, Giuliano; Smolek, Michael K; Orzalesi, Nicola; De Cilla', Stefano; Autelitano, Alessandro; Fogagnolo, Paolo

2015-01-01

To evaluate Compass, a new instrument for glaucoma screening and diagnosis that combines scanning ophthalmoscopy, automated perimetry, and eye tracking. A total of 320 human subjects (200 normal, 120 with glaucoma) underwent full ophthalmological evaluation and perimetric evaluation using the Humphrey SITA standard 24° test (HFA), and the Compass test that consisted of a full-threshold program on the central 24° with a photograph of the central 30° of the retina. A subgroup of normal subjects and glaucoma patients underwent a second Compass test during the same day in order to study test-retest variability. After exclusion of 30 patients due to protocol rules, a database was created to compare the Compass to the HFA, and to evaluate retinal image quality and fixation stability. The difference in mean sensitivity between Compass and HFA was -1.02 ± 1.55 dB in normal subjects (p<0.001) and -1.01 ± 2.81 dB in glaucoma (p<0.001). Repeatability SD for the average sensitivity was 1.53 for normal subjects and 1.84 for glaucoma. Test time with the Compass was 634±96 s (607±78 for normals, 678±108 for glaucoma). Compass analysis showed the percentage of fixation within the central 1° was 86.6% in normal subjects, and 79.3% in glaucoma patients. Color image quality was sufficient for diagnostic use in >65% of cases; Image-based diagnosis was in accordance with the initial diagnosis in 85% of the subjects. Based on preliminary results, Compass showed useful diagnostic characteristics for the study of glaucoma, and combined morphological information with functional data.

Increased (/sup 125/I)trypsin-binding in serum from cystic fibrosis patients

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

Cox, K.L.; Frates, R.C. Jr.; Sheikholislam, B.M.

1982-01-01

The capacities of normal and cystic fibrosis (CF) sera to bind to exogenous human (/sup 125/I)trypsin were compared. Sera from eight older CF patients bound significantly more exogenous human (/sup 125/I)trypsin than did sera from eight normal subjects (p less than 0.001). Disregarding the increased trypsin-binding (TB) of CF sera, serum immunoreactive trypsinogen (SIRT) levels were not detectable in these eight older CF patients. However, when SIRT levels were corrected for TB, four CF patients had normal SIRT concentrations and four had low but detectable SIRT levels. As compared to five normal newborns' sera, serum from a newborn with CFmore » had normal TB and the SIRT levels were very high. In conclusion, increased TB in CF serum lowers results of SIRT assays. Therefore, unless SIRT levels are corrected for TB, results obtained from currently available SIRT kits may be invalid.« less

Reduction of blood serum cholesterol

NASA Technical Reports Server (NTRS)

Winitz, M. (Inventor)

1974-01-01

By feeding a human subject as the sole source of sustenance a defined diet wherein the carbohydrate consists substantially entirely of glucose, maltose or a polysaccharide of glucose, the blood serum cholesterol level of the human subject is substantially reduced. If 25 percent of the carbohydrate is subsequently supplied in the form of sucrose, an immediate increase from the reduced level is observed. The remainder of the defined diet normally includes a source of amino acids, such as protein or a protein hydrolysate, vitamins, minerals and a source of essential fatty acid.

Peripheral benzodiazepine receptors are decreased during cocaine withdrawal in humans.

PubMed

Javaid, J I; Notorangelo, M P; Pandey, S C; Reddy, P L; Pandey, G N; Davis, J M

1994-07-01

In the present study, homovanillic acid in plasma (pHVA) and benzodiazepine receptors (3H-PK11195 binding) in neutrophil membranes were determined in blood obtained from cocaine-dependent (DSM-III-R) adult male inpatients at baseline-(within 72 hr of last cocaine use) and after 3 weeks of cocaine abstinence, and normal controls. The mean (+/- SEM) pHVA at baseline (10.3 ng/ml +/- 1.1) was similar to normals and did not change after 3 weeks of cocaine abstinence. Similarly, the binding indices of benzodiazepine receptors in cocaine-dependent subjects as a group were not significantly different than in normal controls. In 10 cocaine-dependent subjects, however, where both blood samples were available, the number of 3H-PK11195 binding sites was significantly (p < 0.05) decreased after 3 weeks of cocaine abstinence (mean +/- sem: Bmax = 6371 +/- 657 fmol/mg protein) compared with baseline (Bmax = 7553 +/- 925 fmol/mg protein), although there were no differences in the binding affinity (mean +/- sem: KD = 8.6 +/- 1.2 nmol/L after 3 weeks of abstinence compared with 8.1 +/- 1.0 nmol/L at baseline). These preliminary results suggest that peripheral benzodiazepine receptors may play an important role in the pathophysiology of cocaine withdrawal in cocaine-dependent human subjects.

Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans.

PubMed

Cui, Jian; McQuillan, Patrick M; Blaha, Cheryl; Kunselman, Allen R; Sinoway, Lawrence I

2012-08-15

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P < 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects.

The biology of human psychosexual differentiation.

PubMed

Gooren, Louis

2006-11-01

Most attempts to identify biological underpinnings of gender identity and sexual orientation in humans have investigated effects of sex steroids, so pivotal in the differentiation of the genitalia, showing strong parallels between animals and the human. The information on humans is derived from the so-called 'experiments of nature', clinical entities with a lesser-than-normal androgen exposure in XY subjects and a higher than normal androgen exposure in XX subjects. Prenatal androgenization appears to predispose to a male gender identity development, but apparently not decisively since 40-50% of 46,XY intersexed children with a history of prenatal androgen exposure do not develop a male gender identity. Obviously, male-to-female transsexuals, with a normal androgen exposure prenatally (there is no serious evidence to the contrary) develop a female gender identity, through unknown biological mechanisms apparently overriding the effects of prenatal androgens. The latest studies in 46, XX subjects exposed to prenatal androgens show that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior but does not lead to gender confusion/dysphoria. The example of female-to-male transsexuals, without evidence of prenatal androgen exposure, indicates that a male gender identity can develop without a significant androgen stimulus. So we are far away from any comprehensive understanding of hormonal imprinting on gender identity formation. Brain studies in homosexuals have not held up in replication studies or are in need of replication in transsexuals. Genetic studies and the fraternal birth order hypothesis provide indications of familial clustering of homosexuality but in many homosexuals these genetic patterns cannot be identified. The biological explanations advanced for the birth order hypothesis lack any experimental support.

In vivo laser confocal microscopy of Bowman's layer of the cornea.

PubMed

Kobayashi, Akira; Yokogawa, Hideaki; Sugiyama, Kazuhisa

2006-12-01

To investigate in vivo microstructures of Bowman's layer in normal human subjects using a cornea-specific in vivo laser scanning confocal microscope (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT2-RCM). Single-center, prospective, observational case series. Nineteen normal volunteers (10 male, 9 female; mean age, 46.2+/-21.7 years [range, 18-77]). The central and peripheral cornea, specifically the epithelium, Bowman's layer, and its subjacent stroma, were examined using the HRT2-RCM. Selected images of the corneal layers were evaluated qualitatively for the shape and degree of light reflection of the microstructures. In all subjects, normal epithelial (superficial, wing, basal) cells, subbasal nerve plexus, Bowman's layer, and its subjacent stoma were observed clearly. However, in all subjects, polymorphic structures composed of fibrillar materials with less reflectivity than corneal nerves were observed beneath Bowman's layer. After application of pressure by a Tomo-cap, we observed numerous ridges that protruded into the epithelial basal and wing cell layers. Superficial stromal striae were also observed. These ridges and striae corresponded exactly to the orientation of the fibrous structures located beneath the epithelial cells. We report for the first time, the presence of polymorphic structures composed of fibrillar materials (K-structures) beneath Bowman's layer in normal human subjects, detected by HRT2-RCM. We surmise that these microstructures may correspond to the modified and condensed anterior stromal collagen fibers/lamellae that merge into Bowman's layer and that these fibrillar materials may be responsible for the formation of the anterior corneal mosaic. Further investigation of these microstructures in diseased eyes may provide insights into their pathophysiologic role in Bowman's layer.

Anthropometry. A Bibliography with Abstracts

DTIC Science & Technology

1975-08-01

nces fro signific e shirt- (Author) o US per ach ions wea ed. angu obta m t ant slee AF pilots sonal p en velone : d) s ring com...side measured bility. s of the human neck which may influence a person’s • whiplash ’ injury during lateral impact have oeen mal subjects. Subjects...group of lb subjects Deing n average stature close to the both ptrcentile tor data include: measures of head , neck and body anding and normal

Effect of amiloride and saline on nasal mucociliary clearance and potential difference in cystic fibrosis and normal subjects.

PubMed Central

Middleton, P. G.; Geddes, D. M.; Alton, E. W.

1993-01-01

BACKGROUND--Mucociliary clearance is an important component of pulmonary defence. Maximum clearance is thought to depend on an optimal depth of the sol layer, allowing the most efficient interaction between the cilia and the overlying mucus layer. Sodium absorption, the major ion transport in human airways, is thought to be important in the regulation of the depth of the sol layer. In the airways of patients with cystic fibrosis sodium absorption is increased and mucociliary clearance decreased. Amiloride, a sodium channel blocker, has been shown to improve pulmonary mucociliary clearance in patients with cystic fibrosis. However, its effects on nasal mucociliary clearance in either normal subjects or those with cystic fibrosis are unknown. A study was therefore performed to investigate whether nebulised amiloride improves nasal mucociliary clearance in normal or cystic fibrosis subjects. METHODS--Nasal mucociliary clearance was measured by the saccharin clearance technique in 12 normal subjects and 12 with cystic fibrosis. For the control study measurements were made on two consecutive days and the mean time for each subject averaged. For the drug study measurements were also made on two consecutive days, after administration of nasally nebulised amiloride or placebo (saline) in a double blind manner. Nasal potential difference was measured in eight patients with cystic fibrosis after the administration of amiloride or placebo to assess the efficacy of deposition and duration of action. RESULTS--Baseline values of mucociliary clearance were significantly faster in the normal subjects than in those with cystic fibrosis. In both groups mucociliary clearance was increased after both saline and amiloride, with no significant difference between either treatment. As previously reported, baseline nasal potential difference was significantly more negative in the subjects with cystic fibrosis. Amiloride significantly reduced the potential difference for at least 60 minutes in these subjects. CONCLUSIONS--Nebulised saline significantly improves nasal mucociliary clearance in both normal subjects and those with cystic fibrosis. Amiloride did not appear to exert any additional effects in either group of subjects, despite evidence of its efficacy of deposition. PMID:8211871

Detection of human papillomavirus in normal oral cavity in a group of Pakistani subjects using real-time PCR.

PubMed

Gichki, Abdul Samad; Buajeeb, Waranun; Doungudomdacha, Sombhun; Khovidhunkit, Siribang-on Pibooniyom

2012-01-01

Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the β-globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1 μg of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p=0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients.

Use of hydrogen peroxide to assess the sperm susceptibility to oxidative stress in subjects presenting a normal semen profile.

PubMed

Misro, M M; Choudhury, L; Upreti, K; Gautam, D; Chaki, S P; Mahajan, A S; Babbar, R

2004-04-01

Human sperm susceptibility to oxidative stress is vital as it affects various characteristics of sperm function. In the present study, we report a simple, sensitive and quick method of assessing the capacity of the sperms to withstand increased oxidative stress. The basis for the test was derived from the fact that human sperms suspended in Ham's F-10 medium tend to lose the forward progressive motility when co-incubated with H(2)O(2) (600 microm). Replacement of the medium with seminal plasma (1: 1) was able to reduce the loss of sperm motility (40%). Retention of sperm motility in semen (0-30%) following 10 min of H(2)O(2) (600 microm) exposure was taken as the criteria for delineating the quality of sperm as poor, moderate, good and excellent types. The protocol was tested in 87 subjects presenting a normal semen profile. On the basis of this test, 44% of the semen samples were classified as poor and the rest as moderate, good or excellent. Lipid peroxidation was found higher in the sperms from the 'poor' category. Activities of superoxide dismutase and catalase were also significantly elevated in the seminal plasma of these subjects as compared with combined categories of good or excellent. The test described here can be used routinely in laboratory investigations to assess sperm susceptibility to oxidative stress in subjects presenting a normal semen profile.

Statokinesigram normalization method.

PubMed

de Oliveira, José Magalhães

2017-02-01

Stabilometry is a technique that aims to study the body sway of human subjects, employing a force platform. The signal obtained from this technique refers to the position of the foot base ground-reaction vector, known as the center of pressure (CoP). The parameters calculated from the signal are used to quantify the displacement of the CoP over time; there is a large variability, both between and within subjects, which prevents the definition of normative values. The intersubject variability is related to differences between subjects in terms of their anthropometry, in conjunction with their muscle activation patterns (biomechanics); and the intrasubject variability can be caused by a learning effect or fatigue. Age and foot placement on the platform are also known to influence variability. Normalization is the main method used to decrease this variability and to bring distributions of adjusted values into alignment. In 1996, O'Malley proposed three normalization techniques to eliminate the effect of age and anthropometric factors from temporal-distance parameters of gait. These techniques were adopted to normalize the stabilometric signal by some authors. This paper proposes a new method of normalization of stabilometric signals to be applied in balance studies. The method was applied to a data set collected in a previous study, and the results of normalized and nonnormalized signals were compared. The results showed that the new method, if used in a well-designed experiment, can eliminate undesirable correlations between the analyzed parameters and the subjects' characteristics and show only the experimental conditions' effects.

Accumulation of methylsulfonylmethane in the human brain: identification by multinuclear magnetic resonance spectroscopy.

PubMed

Lin, A; Nguy, C H; Shic, F; Ross, B D

2001-09-15

Methylsulfonylmethane (MSM) is a widely available 'alternative' medicine. In vivo magnetic resonance spectroscopy (MRS) was used to detect and quantify MSM in the brains of four patients with memory loss and in three normal volunteers all of who had ingested MSM at the recommended doses of 1-3 g daily. MSM was detected in all subjects at concentrations of 0.42-3.40 mmole/kg brain and was equally distributed between gray and white matter. MSM was undetectable in drug-naïve normal subjects (N=25), patients screened for 'toxic exposure' (N=50) or patients examined with 1H MRS for the diagnosis of probable Alzheimer Disease (N=520) between 1991 and 2001. No adverse clinical or neurochemical effects were observed. Appearance of MSM in significant concentrations in the human brain indicates ready transfer across the intact blood-brain barrier, of a compound with no known medical benefits.

Benzodiazepine sensitivity in normal human subjects.

PubMed

Hommer, D W; Matsuo, V; Wolkowitz, O; Chrousos, G; Greenblatt, D J; Weingartner, H; Paul, S M

1986-06-01

Increasing intravenous doses of diazepam or placebo were administered to ten healthy normal volunteers, and the changes in saccadic eye velocity, self-rated sedation and anxiety, and plasma cortisol and growth hormone concentrations were measured. Diazepam administration (4.4 to 140 micrograms/kg, cumulative dose) resulted in a dose-dependent decrease in saccadic eye velocity and plasma cortisol level as well as a dose-dependent increase in self-rated sedation and plasma growth hormone level. Self-rated anxiety was unaffected in these relatively nonanxious subjects. The diazepam-induced changes in saccadic eye velocity, sedation, and growth hormone and cortisol levels were highly correlated with each other and with increasing plasma diazepam concentration. These results are consistent with a benzodiazepine receptor-mediated action of diazepam. The highly quantifiable and dose-dependent decrease in saccadic eye velocity by benzodiazepines should make this a useful measure of benzodiazepine receptor sensitivity in humans.

Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency or leptin administration in humans.

PubMed

Kang, Eun Seok; Magkos, Faidon; Sienkiewicz, Elizabeth; Mantzoros, Christos S

2011-06-01

Animal and in vitro studies indicate that leptin alleviates starvation-induced reduction in circulating vaspin and stimulates the production of visfatin. We thus examined whether vaspin and visfatin are affected by short- and long-term energy deprivation and leptin administration in human subjects in vivo. We measured circulating levels of vaspin and visfatin i) before and after 72 h of starvation (leading to severe hypoleptinemia) with or without leptin administration in replacement doses in 13 normal-weight subjects, ii) before and after 72 h of starvation with leptin administration in pharmacological doses in 13 lean and obese subjects, iii) during chronic energy deficiency in eight women with hypothalamic amenorrhea on leptin replacement for 3 months, and iv) during chronic energy deficiency in 18 women with hypothalamic amenorrhea on leptin replacement or placebo for 3 months. Acute starvation decreased serum leptin to 21% of baseline values, (P=0.002) but had no significant effect on vaspin and visfatin concentrations (P>0.05). Nor did normalization of leptin levels affect the concentrations of these two adipokines (P>0.9). Leptin replacement in women with hypothalamic amenorrhea did not significantly alter vaspin and visfatin concentrations, whether relative to baseline or placebo administration (P>0.25). Pharmacological doses of leptin did not affect circulating vaspin and visfatin concentrations (P>0.9). Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency leading to hypoleptinemia and are not regulated by leptin in human subjects, indicating that these adipocyte-secreted hormonal regulators of metabolism are independently regulated in humans.

Normalized value coding explains dynamic adaptation in the human valuation process.

PubMed

Khaw, Mel W; Glimcher, Paul W; Louie, Kenway

2017-11-28

The notion of subjective value is central to choice theories in ecology, economics, and psychology, serving as an integrated decision variable by which options are compared. Subjective value is often assumed to be an absolute quantity, determined in a static manner by the properties of an individual option. Recent neurobiological studies, however, have shown that neural value coding dynamically adapts to the statistics of the recent reward environment, introducing an intrinsic temporal context dependence into the neural representation of value. Whether valuation exhibits this kind of dynamic adaptation at the behavioral level is unknown. Here, we show that the valuation process in human subjects adapts to the history of previous values, with current valuations varying inversely with the average value of recently observed items. The dynamics of this adaptive valuation are captured by divisive normalization, linking these temporal context effects to spatial context effects in decision making as well as spatial and temporal context effects in perception. These findings suggest that adaptation is a universal feature of neural information processing and offer a unifying explanation for contextual phenomena in fields ranging from visual psychophysics to economic choice.

Hemispheric asymmetries in the orientation and location of the lateral geniculate nucleus in dyslexia.

PubMed

Giraldo-Chica, Mónica; Schneider, Keith A

2018-05-01

Human brain asymmetry reflects normal specialization of functional roles and may derive from evolutionary, hereditary, developmental, experiential, and pathological factors (Toga & Thompson, 2003). Geschwind and Galaburda (1985) suggested that processing difficulties in dyslexia are due to structural differences between hemispheres. Because of its potential significance to the controversial magnocellular theory of dyslexia, we investigated hemispheric differences in the human lateral geniculate nucleus (LGN), the primary visual relay and control nucleus in the thalamus, in subjects with dyslexia compared to normal readers. We acquired and averaged multiple high-resolution proton density (PD) weighted structural magnetic resonance imaging (MRI) volumes to measure in detail the anatomical boundaries of the LGN in each hemisphere. We observed hemispheric asymmetries in the orientation of the nucleus in subjects with dyslexia that were absent in controls. We also found differences in the location of the LGN between hemispheres in controls but not in subjects with dyslexia. Neither the precise anatomical differences in the LGN nor their functional consequences are known, nor is it clear whether the differences might be causes or effects of dyslexia. Copyright © 2018 John Wiley & Sons, Ltd.

Color analysis of the human airway wall

NASA Astrophysics Data System (ADS)

Gopalakrishnan, Deepa; McLennan, Geoffrey; Donnelley, Martin; Delsing, Angela; Suter, Melissa; Flaherty, Dawn; Zabner, Joseph; Hoffman, Eric A.; Reinhardt, Joseph M.

2002-04-01

A bronchoscope can be used to examine the mucosal surface of the airways for abnormalities associated with a variety of lung diseases. The diagnosis of these abnormalities through the process of bronchoscopy is based, in part, on changes in airway wall color. Therefore it is important to characterize the normal color inside the airways. We propose a standardized method to calibrate the bronchoscopic imaging system and to tabulate the normal colors of the airway. Our imaging system consists of a Pentium PC and video frame grabber, coupled with a true color bronchoscope. The calibration procedure uses 24 standard color patches. Images of these color patches at three different distances (1, 1.5, and 2 cm) were acquired using the bronchoscope in a darkened room, to assess repeatability and sensitivity to illumination. The images from the bronchoscope are in a device-dependent Red-Green-Blue (RGB) color space, which was converted to a tri-stimulus image and then into a device-independent color space sRGB image by a fixed polynomial transformation. Images were acquired from five normal human volunteer subjects, two cystic fibrosis (CF) patients and one normal heavy smoker subject. The hue and saturation values of regions within the normal airway were tabulated and these values were compared with the values obtained from regions within the airways of the CF patients and the normal heavy smoker. Repeated measurements of the same region in the airways showed no measurable change in hue or saturation.

The Effects on Muscle Activation of Flatfoot during Gait According to the Velocity on an Ascending Slope.

PubMed

Lee, Chang-Ryeol; Kim, Myoung-Kwon

2014-05-01

[Purpose] This study determined the difference between flatfeet and normal feet in humans on an ascending slope using electromyography (EMG). [Subjects] This study was conducted on 30 adults having normal feet (n=15) and flatfeet (n=15), all of whom were 21 to 30 years old. [Methods] A treadmill (AC5000M, SCIFIT,) was used to analyze kinematic features during gait. These features were analyzed at slow, normal, and fast gait velocities on an ascending slope. A surface electromyogram (TeleMyo 2400T, Noraxon Co., USA) was used to measure muscle activity changes. [Results] The activities of most muscles in the subjects with flatfeet were significantly different from the muscle activities in the subjects with normal feet at different gait velocities on an ascending slope. There were significant differences in the vastus medialis and abductor hallucis muscles. [Conclusion] Because muscle activation of the vastus medialis in relation to stability of the lower extremity has a tendency to increase with an increase in gait velocity on an ascending slope, we hypothesized that higher impact transfer to the knee joints occurs in subjects with flatfeet due to the lack of a medial longitudinal arch and that the abductor halluces muscles, which provide dynamic stability to the medial longitudinal arches, do not activate well when they are needed in subjects with flatfeet.

Rod Electroretinograms Elicited by Silent Substitution Stimuli from the Light-Adapted Human Eye

PubMed Central

Maguire, John; Parry, Neil R. A.; Kremers, Jan; Kommanapalli, Deepika; Murray, Ian J.; McKeefry, Declan J.

2016-01-01

Purpose To demonstrate that silent substitution stimuli can be used to generate electroretinograms (ERGs) that effectively isolate rod photoreceptor function in humans without the need for dark adaptation, and that this approach constitutes a viable alternative to current clinical standard testing protocols. Methods Rod-isolating and non-isolating sinusoidal flicker stimuli were generated on a 4 primary light-emitting diode (LED) Ganzfeld stimulator to elicit ERGs from participants with normal and compromised rod function who had not undergone dark-adaptation. Responses were subjected to Fourier analysis, and the amplitude and phase of the fundamental were used to examine temporal frequency and retinal illuminance response characteristics. Results Electroretinograms elicited by rod-isolating silent substitution stimuli exhibit low-pass temporal frequency response characteristics with an upper response limit of 30 Hz. Responses are optimal between 5 and 8 Hz and between 10 and 100 photopic trolands (Td). There is a significant correlation between the response amplitudes obtained with the silent substitution method and current standard clinical protocols. Analysis of signal-to-noise ratios reveals significant differences between subjects with normal and compromised rod function. Conclusions Silent substitution provides an effective method for the isolation of human rod photoreceptor function in subjects with normal as well as compromised rod function when stimuli are used within appropriate parameter ranges. Translational Relevance This method of generating rod-mediated ERGs can be achieved without time-consuming periods of dark adaptation, provides improved isolation of rod- from cone-based activity, and will lead to the development of faster clinical electrophysiologic testing protocols with improved selectivity. PMID:27617180

Human locognosic acuity on the arm varies with explicit and implicit manipulations of attention: implications for interpreting elevated tactile acuity on an amputation stump.

PubMed

O'Boyle, D J; Moore, C E; Poliakoff, E; Butterworth, R; Sutton, A; Cody, F W

2001-06-01

In Experiment 1, normal subjects' ability to localize tactile stimuli (locognosia) delivered to the upper arm was significantly higher when they were instructed explicitly to direct their attention selectively to that segment than when they were instructed explicitly to distribute their attention across the whole arm. This elevation of acuity was eliminated when subjects' attentional resources were divided by superimposition of an effortful, secondary task during stimulation. In Experiment 2, in the absence of explicit attentional instruction, subjects' locognosic acuity on one of three arm segments was significantly higher when stimulation of that segment was 2.5 times more probable than that of stimulation of the other two segments. We surmise that the attentional mechanisms responsible for such modulations of locognosic acuity in normal subjects may contribute to the elevated sensory acuity observed on the stumps of amputees.

Default, Cognitive and Affective Brain Networks in Human Tinnitus

DTIC Science & Technology

Tinnitus is a major health problem among those currently and formerly in military service. This project hypothesizes that many of the clinically...significant, non-auditory aspects of the tinnitus condition involve two major brain networks: the cognitive control network (CCN) and the default mode...function can be assessed. Subjects in three groups are being compared: (1) control subjects with clinically-normal hearing thresholds and no tinnitus

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

PubMed

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

2010-09-01

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

An optimal state estimation model of sensory integration in human postural balance

NASA Astrophysics Data System (ADS)

Kuo, Arthur D.

2005-09-01

We propose a model for human postural balance, combining state feedback control with optimal state estimation. State estimation uses an internal model of body and sensor dynamics to process sensor information and determine body orientation. Three sensory modalities are modeled: joint proprioception, vestibular organs in the inner ear, and vision. These are mated with a two degree-of-freedom model of body dynamics in the sagittal plane. Linear quadratic optimal control is used to design state feedback and estimation gains. Nine free parameters define the control objective and the signal-to-noise ratios of the sensors. The model predicts statistical properties of human sway in terms of covariance of ankle and hip motion. These predictions are compared with normal human responses to alterations in sensory conditions. With a single parameter set, the model successfully reproduces the general nature of postural motion as a function of sensory environment. Parameter variations reveal that the model is highly robust under normal sensory conditions, but not when two or more sensors are inaccurate. This behavior is similar to that of normal human subjects. We propose that age-related sensory changes may be modeled with decreased signal-to-noise ratios, and compare the model's behavior with degraded sensors against experimental measurements from older adults. We also examine removal of the model's vestibular sense, which leads to instability similar to that observed in bilateral vestibular loss subjects. The model may be useful for predicting which sensors are most critical for balance, and how much they can deteriorate before posture becomes unstable.

Corroboration of in vivo cartilage pressures with implications for synovial joint tribology and osteoarthritis causation.

PubMed

Morrell, Kjirste C; Hodge, W Andrew; Krebs, David E; Mann, Robert W

2005-10-11

Pressures on normal human acetabular cartilage have been collected from two implanted instrumented femoral head hemiprostheses. Despite significant differences in subjects' gender, morphology, mobility, and coordination, in vivo pressure measurements from both subjects covered similar ranges, with maximums of 5-6 MPa in gait, and as high as 18 MPa in other movements. Normalized for subject weight and height (nMPa), for free-speed walking the maximum pressure values were 25.2 for the female subject and 24.5 for the male subject. The overall maximum nMPa values were 76.2 for the female subject during rising from a chair at 11 months postoperative and 82.3 for the male subject while descending steps at 9 months postoperative. These unique in vivo data are consistent with corresponding cadaver experiments and model analyses. The collective results, in vitro data, model studies, and now corroborating in vivo data support the self-pressurizing "weeping" theory of synovial joint lubrication and provide unique information to evaluate the influence of in vivo pressure regimes on osteoarthritis causation and the efficacy of augmentations to, and substitutions for, natural cartilage.

Investigation of alterations in multifractality in optical coherence tomographic images of in vivo human retina

NASA Astrophysics Data System (ADS)

Das, Nandan Kumar; Mukhopadhyay, Sabyasachi; Ghosh, Nirmalya; Chhablani, Jay; Richhariya, Ashutosh; Divakar Rao, Kompalli; Sahoo, Naba Kishore

2016-09-01

Optical coherence tomography (OCT) enables us to monitor alterations in the thickness of the retinal layer as disease progresses in the human retina. However, subtle morphological changes in the retinal layers due to early disease progression often may not lead to detectable alterations in the thickness. OCT images encode depth-dependent backscattered intensity distribution arising due to the depth distributions of the refractive index from tissue microstructures. Here, such depth-resolved refractive index variations of different retinal layers were analyzed using multifractal detrended fluctuation analysis, a special class of multiresolution analysis tools. The analysis extracted and quantified microstructural multifractal information encoded in normal as well as diseased human retinal OCT images acquired in vivo. Interestingly, different layers of the retina exhibited different degrees of multifractality in a particular retina, and the individual layers displayed consistent multifractal trends in healthy retinas of different human subjects. In the retinal layers of diabetic macular edema (DME) subjects, the change in multifractality manifested prominently near the boundary of the DME as compared to the normal retinal layers. The demonstrated ability to quantify depth-resolved information on multifractality encoded in OCT images appears promising for the early diagnosis of diseases of the human eye, which may also prove useful for detecting other types of tissue abnormalities from OCT images.

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

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

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

1979-09-01

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

Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population.

PubMed

Rong, Rong; Tao, Ya-Xiong; Cheung, Bernard M Y; Xu, Aimin; Cheung, Grace C N; Lam, Karen S L

2006-08-01

Mutations in the melanocortin-4 receptor gene (MC4R) are the most common monogenic form of human obesity. However, the contribution of MC4R mutations to obesity in Chinese has not been investigated. We studied the frequency of MC4R mutations in an obese southern Chinese population and the functional consequences of the novel variants identified. We screened for MC4R mutations in 227 obese [body mass index (BMI) 35.29 +/- 5.75 kg/m2] and 100 lean (BMI 21.57 +/- 0.29 kg/m2) southern Chinese subjects using PCR-direct sequencing. In vitro functional studies, including cell surface expression, ligand binding, and cyclic adenosine monophosphate (cAMP) accumulation, were performed to examine the functional properties of three novel missense mutations. Apart from two previously reported polymorphisms, V103I and -176 A > C, three novel missense heterozygous variants (Y35C, C40R and M218T) were identified. The polymorphisms -176 A > C and Y35C were detected in both obese and normal subjects with similar frequency. C40R was identified only in an obese subject. Pedigree analysis revealed M218T carriers in both lean and obese subjects. The prevalence of V103I carriers in normal-weight controls was significantly higher than that in obese subjects (5.3%vs. 1.3%, P < 0.05). In vitro functional studies showed that all three novel missense variants have normal functions. Two known polymorphisms and three novel variants of the MC4R were identified. No overt functional defects were observed for the three novel MC4R variants, suggesting that they might not be the cause of obesity in variant carriers.

Plasma galanin concentrations in obese, normal weight and anorectic women.

PubMed

Invitti, C; Brunani, A; Pasqualinotto, L; Dubini, A; Bendinelli, P; Maroni, P; Cavagnini, F

1995-05-01

Galanin is believed to play a role in the control of eating behavior. No information is available on its concentrations in the biological fluids in human obesity, and this study aimed to clarify this. We measured plasma galanin and serum insulin levels in 30 obese, 35 normal weight and 11 anorectic women. Mean galanin values were quite similar in obese and control subjects (76.8 +/- 3.20 vs 76.1 +/- 2.33 pg/ml) and only slightly reduced in anorectic patients (67.9 +/- 2.30 pg/ml). Insulin levels were significantly increased and decreased in obese and anorectic patients, respectively, compared to controls. Insulin correlated positively with BMI in the whole group of subjects studied (r = 0.72, P < 0.0001) and in the obese subgroup (r = 0.56, P < 0.02). No correlations could be detected between WH ratio, insulin and galanin concentrations and between galanin and BMI. In conclusion, plasma galanin concentrations appear to be comparable in obese, normal weight and anorectic subjects. This does not exclude a role of galanin in the regulation of eating behavior since variations of the peptide in discrete brain areas may not be detectable in general circulation and peripheral sources of the peptide may contribute to its plasma levels. Also, our data suggest that galanin does not play a major role in the regulation of insulin secretion in humans.

Hereditary deficiency of the sixth component of complement in man. II. Studies of hemostasis.

PubMed Central

Heusinkveld, R S; Leddy, J P; Klemperer, M R; Breckenridge, R T

1974-01-01

Prompted by previous observations of defective blood clotting in rabbits deficient in the sixth component of complement (C6), an evaluation was made of the hemostatic functions of the homozygous proband of a newly recognized human kindred with hereditary C6 deficiency. This human subject, who had no clinical evidence of a bleeding disorder, exhibited a total lack of C6 by functional and immunoprecipitin assays of serum or plasma. Standard tests of hemostatic function were normal; however, when the whole blood clotting time was measured at 25 degrees C in plastic tubes, it was at the upper range of our normal values. In confirmation of this observation, prothrombin consumption, when performed at 37 degrees C in plastic tubes, was at the lower range of normal. Inulin and endotoxin, in concentrations shown to cause activation of human complement, had little or no effect on clotting times or prothrombin consumption of normal or C6-deficient human blood. These observations indicate that absence of C6 does not have a significant effect on hemostatic function in man. In the light of other investigations, the observed differences in clotting function between C6-deficient human blood and C6-deficient rabbit blood could be due to species differences governing the susceptibility of platelets to complement activation. PMID:11344569

Tryptophan as key biomarker to detect gastrointestinal tract cancer using non-negative biochemical analysis of native fluorescence and Stokes Shift spectroscopy

NASA Astrophysics Data System (ADS)

Wang, Leana; Zhou, Yan; Liu, Cheng-hui; Zhou, Lixin; He, Yong; Pu, Yang; Nguyen, Thien An; Alfano, Robert R.

2015-03-01

The objective of this study was to find out the emission spectral fingerprints for discrimination of human colorectal and gastric cancer from normal tissue in vitro by applying native fluorescence. The native fluorescence (NFL) and Stokes shift spectra of seventy-two human cancerous and normal colorectal (colon, rectum) and gastric tissues were analyzed using three selected excitation wavelengths (e.g. 300 nm, 320 nm and 340 nm). Three distinct biomarkers, tryptophan, collagen and reduced nicotinamide adenine dinucleotide hydrate (NADH), were found in the samples of cancerous and normal tissues from eighteen subjects. The spectral profiles of tryptophan exhibited a sharp peak in cancerous colon tissues under a 300 nm excitation when compared with normal tissues. The changes in compositions of tryptophan, collagen, and NADH were found between colon cancer and normal tissues under an excitation of 300 nm by the non-negative basic biochemical component analysis (BBCA) model.

Effects of water immersion on plasma catecholamines in normal humans

NASA Technical Reports Server (NTRS)

Epstein, M.; Johnson, G.; Denunzio, A. G.

1983-01-01

An investigation was conducted in order to determine whether water immersion to the neck (NI) alters plasma catecholamines in normal humans. Eight normal subjects were studied during a seated control study (C) and during 4 hr of NI, and the levels of norepinephrine (NE) and epinephrine (E) as determined by radioenzymatic assay were measured hourly. Results show that despite the induction of a marked natriuresis and diuresis indicating significant central hypervolemia, NI failed to alter plasma NE or E levels compared with those of either C or the corresponding prestudy 1.5 hr. In addition, the diuresis and natriuresis was found to vary independently of NE. These results indicate that the response of the sympathetic nervous system to acute volume alteration may differ from the reported response to chronic volume expansion.

Diurnal Variation of Sweet Taste Recognition Thresholds Is Absent in Overweight and Obese Humans

PubMed Central

Sanematsu, Keisuke; Nakamura, Yuki; Nomura, Masatoshi; Shigemura, Noriatsu; Ninomiya, Yuzo

2018-01-01

Sweet taste thresholds are positively related to plasma leptin levels in normal weight humans: both show parallel diurnal variations and associations with postprandial glucose and insulin rises. Here, we tested whether this relationship also exists in overweight and obese (OW/Ob) individuals with hyperleptinemia. We tested 36 Japanese OW/Ob subjects (body mass index (BMI) > 25 kg/m2) for recognition thresholds for various taste stimuli at seven different time points from 8:00 a.m. to 10:00 p.m. using the staircase methodology, and measured plasma leptin, insulin, and blood glucose levels before each taste threshold measurement. We also used the homeostatic model assessment of insulin resistance (HOMA-IR) to evaluate insulin resistance. The results demonstrated that, unlike normal weight subjects, OW/Ob subjects showed no significant diurnal variations in the recognition thresholds for sweet stimuli but exhibited negative associations between the diurnal variations of both leptin and sweet recognition thresholds and the HOMA-IR scores. These findings suggest that in OW/Ob subjects, the basal leptin levels (~20 ng/mL) may already exceed leptin’s effective concentration for the modulation of sweet sensitivity and that this leptin resistance-based attenuation of the diurnal variations of the sweet taste recognition thresholds may also be indirectly linked to insulin resistance in OW/Ob subjects. PMID:29498693

Comparison between Alzheimer's disease and subcortical vascular dementia: attentional cortex study in functional magnetic resonance imaging.

PubMed

Li, C; Zheng, J; Wang, J; Gui, L

2011-01-01

Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and the Stroop test were used to assess attentional cortex activation in patients with Alzheimer's disease, subcortical vascular dementia, and normal control subjects. Patients with Alzheimer's disease and subcortical vascular dementia demonstrated similar locations of cortical activation, including the bilateral middle and inferior frontal gyri, anterior cingulate and inferior parietal lobule in response to Stroop colour word stimuli. This activation was distinctly decreased in patients with dementia compared with normal control subjects. Different regions of the brain were activated in patients with Alzheimer's disease and subcortical vascular dementia compared with normal controls. fMRI is a useful tool for the study of dementia in humans and has some potential diagnostic value. Further studies with larger numbers of participants are required.

EOSINOPHIL INFLUX TO THE NASAL AIRWAY FOLLOWING LOCAL, LOW-LEVEL LPS CHALLENGE IN HUMANS

EPA Science Inventory

Background: Recent obervations show that atopic asthmatic subjects have increased sensitivity to respirable endotoxin (or LPS) compared with normal persons. In vitro studies demonstrate that LPS enchances eosinophil survival. These obervations suggest that the effects of inhal...

Eye-Target Synchrony and Attention

NASA Astrophysics Data System (ADS)

Contreras, R.; Kolster, R.; Basu, S.; Voss, H. U.; Ghajar, J.; Suh, M.; Bahar, S.

2007-03-01

Eye-target synchrony is critical during smooth pursuit. We apply stochastic phase synchronization to human pursuit of a moving target, in both normal and mild traumatic brain injured (TBI) subjects. Smooth pursuit utilizes the same neural networks used by attention. To test whether smooth pursuit is modulated by attention, subjects tracked a target while loaded with tasks involving working memory. Preliminary results suggest that additional cognitive load increases normal subjects' performance, while the effect is reversed in TBI patients. We correlate these results with eye-target synchrony. Additionally, we correlate eye-target synchrony with frequency of target motion, and discuss how the range of frequencies for optimal synchrony depends on the shift from attentional to automatic-response time scales. Synchrony deficits in TBI patients can be correlated with specific regions of brain damage imaged with diffusion tensor imaging (DTI).

Evaluation of concentric left ventricular geometry in humans: evidence for age-related systematic underestimation.

PubMed

de Simone, Giovanni; Daniels, Stephen R; Kimball, Thomas R; Roman, Mary J; Romano, Carmela; Chinali, Marcello; Galderisi, Maurizio; Devereux, Richard B

2005-01-01

There might be limitations in identifying concentric left ventricular (LV) geometry by ratio of diastolic posterior wall thickness (WT(p)) to cavity radius, defined as relative wall thickness (RWT(p)). This study has been designed to evaluate age effects on RWT(p). WT(p), mean of septal thickness and WT(p) (WT(m)), and cavity radius were cross-sectionally evaluated in 766 1- to 85-year-old, normotensive, nonobese subjects and 331 hypertensive Italians (used as a test series). RWT(p) > or =0.43 defined "traditional" concentric LV geometry. The ratios WT(m)/radius (RWT(m)) and RWT(p) increased by 0.005 and 0.006 per year of age in the age stratum up to 17 years and by 0.002 in the older age stratum (18 years or older; all P<0.0001). Thus, RWT(m) and RWT(p) were normalized to average age in both age strata (10 and 46 years) by age-specific regression coefficients. The 90th and 95th percentiles of age-normalized RWT(p) or RWT(m) were 0.40 and 0.42 or 0.41 and 0.43, respectively, in adults and 0.36 and 0.39 or 0.36 and 0.38, respectively in young subjects. In hypertensive subjects, traditional RWT(p) cutoff identified 74 subjects (22%) with concentric LV geometry; by 95th or 90th normal percentiles, normalized RWT(m) identified 112 (34%), or 149 (45%) subjects with concentric LV geometry, and normalized RWT(p) 29% and 39%, respectively (all P<0.0001 versus unadjusted RWT(p)). Thus, prevalence of concentric LV geometry increases with age-normalized RWT. Accordingly, we suggest that concentric LV hypertrophy be defined by coexistence of high LV mass with age-normalized RWT(m) >0.41 or RWT(p) >0.40. Further studies are required to establish prognostic implications of our findings.

The biologic effects of grounding the human body during sleep as measured by cortisol levels and subjective reporting of sleep, pain, and stress.

PubMed

Ghaly, Maurice; Teplitz, Dale

2004-10-01

Diurnal cortisol secretion levels were measured and circadian cortisol profiles were evaluated in a pilot study conducted to test the hypothesis that grounding the human body to earth during sleep will result in quantifiable changes in cortisol. It was also hypothesized that grounding the human body would result in changes in sleep, pain, and stress (anxiety, depression, irritability), as measured by subjective reporting. Twelve (12) subjects with complaints of sleep dysfunction, pain, and stress were grounded to earth during sleep for 8 weeks in their own beds using a conductive mattress pad. Saliva tests were administered to establish pregrounding baseline cortisol levels. Levels were obtained at 4-hour intervals for a 24-hour period to determine the circadian cortisol profile. Cortisol testing was repeated at week 6. Subjective symptoms of sleep dysfunction, pain, and stress were reported daily throughout the 8-week test period. Measurable improvements in diurnal cortisol profiles were observed, with cortisol levels significantly reduced during night-time sleep. Subjects' 24-hour circadian cortisol profiles showed a trend toward normalization. Subjectively reported symptoms, including sleep dysfunction, pain, and stress, were reduced or eliminated in nearly all subjects. Results indicate that grounding the human body to earth ("earthing") during sleep reduces night-time levels of cortisol and resynchronizes cortisol hormone secretion more in alignment with the natural 24-hour circadian rhythm profile. Changes were most apparent in females. Furthermore, subjective reporting indicates that grounding the human body to earth during sleep improves sleep and reduces pain and stress.

Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency

PubMed Central

Jackson, Robert S.; Creemers, John W.M.; Farooqi, I. Sadaf; Raffin-Sanson, Marie-Laure; Varro, Andrea; Dockray, Graham J.; Holst, Jens J.; Brubaker, Patricia L.; Corvol, Pierre; Polonsky, Kenneth S.; Ostrega, Diane; Becker, Kenneth L.; Bertagna, Xavier; Hutton, John C.; White, Anne; Dattani, Mehul T.; Hussain, Khalid; Middleton, Stephen J.; Nicole, Thomasina M.; Milla, Peter J.; Lindley, Keith J.; O’Rahilly, Stephen

2003-01-01

We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound heterozygosity for novel missense and nonsense mutations. While both subjects shared the phenotypes of obesity, hypoadrenalism, reactive hypoglycemia, and elevated circulating levels of certain prohormones, the clinical presentation of Subject B was dominated by severe refractory neonatal diarrhea, malabsorptive in type. Subsequent investigation of Subject A revealed marked small-intestinal absorptive dysfunction, which was not previously clinically suspected. We postulate that PC1, presumably in the enteroendocrine cells, is essential for the normal absorptive function of the human small intestine. The differences in the nature and severity of presentation between the two cases cannot readily be explained on the basis of allelic heterogeneity, as the nonsense and missense mutations from both subjects had comparably severe effects on the catalytic activity of PC1. Despite Subject A’s negligible PC1 activity, some mature ACTH and glucagon-like peptide 17-36amide were detectable in her plasma, suggesting that the production of these hormones, at least in humans, does not have an absolute dependence on PC1. The presence of severe obesity and the absence of growth retardation in both subjects contrast markedly with the phenotype of mice lacking PC1 and suggest that the precise physiological repertoire of this enzyme may vary between mammalian species. PMID:14617756

Velocity and Vorticity in the Right Heart from 4DMRI Measurements

NASA Astrophysics Data System (ADS)

Hertzberg, Jean; Browning, James; Fenster, Brett

2016-11-01

Measurements of blood flow in the human heart were made using time-resolved 3D cardiac magnetic resonance phase contrast flow imaging (4DMRI). This work focuses on blood flow in the right ventricle (RV) and right atrium (RA) in both normal subjects and patients with pulmonary hypertension (PH). Although cardiac output is unchanged early in the disease, details of the flow field differ between normals and PH patients. In particular, vorticity at peak diastole has been found to correlate with PH. The underlying physics of this difference are being explored by a qualitative visual comparison of 3D flow structures in the vena cava, RA, and RV between healthy subjects and pulmonary hypertensive patients.

Electrophysiological evidence of doubly innervated branched muscle fibers in the human brachioradialis muscle.

PubMed

Lateva, Zoia C; McGill, Kevin C

2007-12-01

Motor-unit action potentials (MUAPs) with unstable satellite (late-latency) components are found in EMG signals from the brachioradialis muscles of normal subjects. We analyzed the morphology and blocking behavior of these MUAPs to determine their anatomical origin. EMG signals were recorded from the brachioradialis muscles of 5 normal subjects during moderate-level isometric contractions. MUAP waveforms, discharge patterns, and blocking were determined using computer-aided EMG decomposition. Twelve MUAPs with unstable satellite potentials were detected, always two together in the same signal. Each MUAP also had a second unstable component associated with its main spike. The blocking behavior of the unstable components depended on how close together the two MUAPs were when they discharged. The latencies and blocking behavior indicate that the unstable components came from branched muscle fibers innervated by two different motoneurons. The satellite potentials were due to action potentials that traveled to the branching point along one branch and back along the other. The blockings were due to action-potential collisions when both motoneurons discharged close together in time. Animal studies suggest that branched muscle fibers may be a normal characteristic of series-fibered muscles. This study adds to our understanding of these muscles in humans.

Influence of regular black tea consumption on tobacco associated DNA damage and HPV prevalence in human oral mucosa.

PubMed

Pal, Debolina; Banerjee, Sarmistha; Indra, Dipanjana; Mandal, Shyamsundar; Dum, Anirudha; Bhowmik, Anup; Panda, Chinmay Kr; Das, Sukta

2007-01-01

Black tea is more widely consumed than green tea worldwide, particularly in India. Therefore, it is necessary to focus attention on black tea with respect to its health promoting and anti-cancer actions. In order to establish the concept that black tea is a potential candidate for cancer prevention, it is important to provide epidemiological evidence derived from investigations of human populations. In view of this, the objective of the present study was to determine the correlation between nature of black tea consumption and DNA damage in normal subjects with or without tobacco habit and oral cancer patients, taking the latter as positive controls. Much experimental evidence points to associations between tobacco habit and HPV 16 and HPV 18 (Human Papilloma virus) infection. But no studies have taken into account the possible confounding effect of black tea consumption on DNA damage along with HPV infection. A pilot study was therefore undertaken. Comet assay was used to evaluate the DNA damage among normal subjects including tobacco users (n = 86), non-tobacco users (n = 45) and Oral cancer patients (n = 37). Percentage of damaged cells was scored in the buccal squamous cells of all subjects mentioned above. HPV analysis was performed on 79 samples (including 37 oral cancer patients). The evaluation of various confounding factors like age, tenure of tobacco habit and tea habit showed significant associations with DNA damage. The observations strongly indicate that regular intake of black tea at least above four cups can reduce tobacco associated DNA damage among normal tobacco users. HPV prevalence was not seen to be associated with age, tenure of tobacco habit or the tea drinking habit.

Estimation of cortical magnification from positional error in normally sighted and amblyopic subjects

PubMed Central

Hussain, Zahra; Svensson, Carl-Magnus; Besle, Julien; Webb, Ben S.; Barrett, Brendan T.; McGraw, Paul V.

2015-01-01

We describe a method for deriving the linear cortical magnification factor from positional error across the visual field. We compared magnification obtained from this method between normally sighted individuals and amblyopic individuals, who receive atypical visual input during development. The cortical magnification factor was derived for each subject from positional error at 32 locations in the visual field, using an established model of conformal mapping between retinal and cortical coordinates. Magnification of the normally sighted group matched estimates from previous physiological and neuroimaging studies in humans, confirming the validity of the approach. The estimate of magnification for the amblyopic group was significantly lower than the normal group: by 4.4 mm deg−1 at 1° eccentricity, assuming a constant scaling factor for both groups. These estimates, if correct, suggest a role for early visual experience in establishing retinotopic mapping in cortex. We discuss the implications of altered cortical magnification for cortical size, and consider other neural changes that may account for the amblyopic results. PMID:25761341

Chemical mapping of anxiety in the brain of healthy humans: an in vivo 1H-MRS study on the effects of sex, age, and brain region.

PubMed

Grachev, I D; Apkarian, A V

2000-12-01

We recently presented results in an in vivo study of human brain chemistry in 'physiologic' anxiety, i.e., the anxiety of normal everyday life. Normal subjects with high anxiety demonstrated increased concentration of chemicals in orbital frontal cortex (OFC) as compared to lower anxiety. In a separate study of aging we demonstrated a decrease of total chemical concentration in OFC of middle-aged subjects, as compared with younger age. This brain region also showed gender dependence; men demonstrating decreased chemical concentration compared to women. We hypothesized that these sex- and age-dependent differences in OFC chemistry changes are a result of anxiety effects on this brain region. In the present study we examined these sex- and age-differential regional brain chemistry changes (as identified by localized in vivo proton magnetic resonance spectroscopy [1H-MRS]) in relation to the state-trait-anxiety (as measured by the State-Trait Anxiety Inventory) in 35 healthy subjects. The concentrations for all nine chemicals of 1H-MRS spectra were measured relative to creatine across multiple brain regions, including OFC in the left hemisphere. Analysis of variance showed anxiety-specific effects on chemical concentration changes in OFC, which were different for both sexes and age groups. Male subjects showed larger effect of anxiety on OFC chemistry as compared to females when the same sex high-anxiety subjects were compared to lower anxiety. Similarly, middle-aged subjects showed larger effect of anxiety on OFC chemistry as compared to younger age when the same age subjects with high anxiety were compared to lower anxiety. Largest effect of anxiety on OFC chemistry was due to changes of N-Acetyl aspartate. The results indicate that the state-trait anxiety has sex- and age-differential patterns on OFC chemistry in healthy humans, providing new information about the neurobiological roots of anxiety.

Biomechanics of normal and pathological gait: implications for understanding human locomotor control.

PubMed

Winter, D A

1989-12-01

The biomechanical (kinetic) analysis of human gait reveals the integrated and detailed motor patterns that are essential in pinpointing the abnormal patterns in pathological gait. In a similar manner, these motor patterns (moments, powers, and EMGs) can be used to identify synergies and to validate theories of CNS control. Based on kinetic and EMG patterns for a wide range of normal subjects and cadences, evidence is presented that both supports and negates the central pattern generator theory of locomotion. Adaptive motor patterns that are evident in peripheral gait pathologies reinforce a strong peripheral rather than a central control. Finally, a three-component subtask theory of human gait is presented and is supported by reference to the motor patterns seen in a normal gait. The identified subtasks are (a) support (against collapse during stance); (b) dynamic balance of the upper body, also during stance; and (c) feedforward control of the foot trajectory to achieve safe ground clearance and a gentle heel contact.

How the Alchemy Makes Inquiry, Evidence, and Exclusion.

ERIC Educational Resources Information Center

Popkewitz, Thomas S.

2002-01-01

Modern teaching and teacher education "magically" transform sciences, social sciences, and humanities. The alchemy of school subjects provides a way to think about frames of reference organizing inquiry and constitutes evidence in teacher education, also obscuring the normalizing and dividing practices of teaching (including…

Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias

ClinicalTrials.gov

2017-08-10

Inherited Cardiac Arrythmias; Long QT Syndrome (LQTS); Brugada Syndrome (BrS); Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT); Early Repolarization Syndrome (ERS); Arrhythmogenic Cardiomyopathy (AC, ARVD/C); Hypertrophic Cardiomyopathy (HCM); Dilated Cardiomyopathy (DCM); Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy); Normal Control Subjects

Clinical study of quantitative diagnosis of early cervical cancer based on the classification of acetowhitening kinetics

NASA Astrophysics Data System (ADS)

Wu, Tao; Cheung, Tak-Hong; Yim, So-Fan; Qu, Jianan Y.

2010-03-01

A quantitative colposcopic imaging system for the diagnosis of early cervical cancer is evaluated in a clinical study. This imaging technology based on 3-D active stereo vision and motion tracking extracts diagnostic information from the kinetics of acetowhitening process measured from the cervix of human subjects in vivo. Acetowhitening kinetics measured from 137 cervical sites of 57 subjects are analyzed and classified using multivariate statistical algorithms. Cross-validation methods are used to evaluate the performance of the diagnostic algorithms. The results show that an algorithm for screening precancer produced 95% sensitivity (SE) and 96% specificity (SP) for discriminating normal and human papillomavirus (HPV)-infected tissues from cervical intraepithelial neoplasia (CIN) lesions. For a diagnostic algorithm, 91% SE and 90% SP are achieved for discriminating normal tissue, HPV infected tissue, and low-grade CIN lesions from high-grade CIN lesions. The results demonstrate that the quantitative colposcopic imaging system could provide objective screening and diagnostic information for early detection of cervical cancer.

The Brainstem Switch for Gaze Shifts in Humans

DTIC Science & Technology

2001-10-25

Page 1 of 4 THE BRAINSTEM SWITCH FOR GAZE SHIFTS IN HUMANS A. N. Kumar1, R. J. Leigh1,2, S. Ramat3 Department of 1Biomedical Engineering, Case...omnipause neurons during gaze shifts. Using the scleral search coil technique, eye movements were measured in seven normal subjects, as they made...voluntary, disjunctive gaze shifts comprising saccades and vergence movements. Conjugate oscillations of small amplitude and high frequency were identified

Photodegradation of carotenoids in human subjects

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

Roe, D.A.

Photodegradation of vitamins in vitro is responsible for large losses of these nutrients in foods, beverages, and semisynthetic liquid formula diets. In vivo photodegradation of vitamins has been reported for riboflavin in jaundiced infants exposed to blue light and for folate in patients with chronic psoriasis given photochemotherapy. Two recent studies of normal subjects have also shown that photodegradation of carotenoids in plasma occurs with cumulative exposure of the skin to an artificial light source having maximal spectral emission in the UVA range. Females showed a larger effect of the UV light on their plasma carotenoid levels than males. Thesemore » observations have identified a need for further investigation of the role of sunlight exposure as a determinant of plasma carotenoid levels and vitamin A status in human subjects.« less

Glymphatic MRI in idiopathic normal pressure hydrocephalus

PubMed Central

Ringstad, Geir; Vatnehol, Svein Are Sirirud; Eide, Per Kristian

2017-01-01

Abstract The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer’s disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging. PMID:28969373

Glymphatic MRI in idiopathic normal pressure hydrocephalus.

PubMed

Ringstad, Geir; Vatnehol, Svein Are Sirirud; Eide, Per Kristian

2017-10-01

The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Insulin absorption and subcutaneous blood flow in normal subjects during insulin-induced hypoglycemia

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

Fernqvist-Forbes, E.; Linde, B.; Gunnarsson, R.

1988-09-01

We studied the effects of insulin-induced hypoglycemia on the absorption of 10 U /sup 125/I-labeled soluble human insulin injected sc in the thigh in 10 normal subjects. The disappearance of /sup 125/I from the injection site was followed by external gamma-counting. Subcutaneous blood flow (ATBF) was measured concomitantly with the 133Xe washout technique. The plasma glucose nadir (mean, 2.0 +/- 0.1 (+/- SE) mmol/L) occurred at 33 +/- 3 min and resulted in maximal arterial plasma epinephrine concentrations of approximately 6 nmol/L. From 30 min before to 60 min after the glucose nadir the (/sup 125/I)insulin absorption rate was depressedmore » compared to that during normoglycemia. The first order disappearance rate constants were reduced by approximately 50% (P less than 0.01) during the first 30-min interval after the glucose nadir. During the same period ATBF increased by 100% (P less than 0.05). The results suggest that in normal subjects the absorption of soluble insulin from a sc depot is depressed in connection with hypoglycemia, despite considerably elevated ATBF.« less

The effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responses to neurokinin A in normal humans in vivo.

PubMed

Cheung, D; Bel, E H; Den Hartigh, J; Dijkman, J H; Sterk, P J

1992-06-01

Neuropeptides such as neurokinin A (NKA) have been proposed as important mediators of bronchoconstriction and airway hyperresponsiveness in asthma. Inhaled NKA causes bronchoconstriction in patients with asthma, but not in normal subjects. This is possibly due to the activity of an endogenous neuropeptide-degrading enzyme: neutral endopeptidase (NEP). We investigated whether a NEP-inhibitor, thiorphan, reveals bronchoconstriction to NKA or NKA-induced changes in airway responsiveness to methacholine in normal humans in vivo. Eight normal male subjects participated in a double-blind crossover study, using thiorphan as pretreatment to NKA challenge. Dose-response curves to inhaled NKA (8 to 1,000 micrograms/ml, 0.5 ml/dose) were recorded on 2 randomized days 1 wk apart, and methacholine tests were performed 48 h before and 24 h after the NKA challenge. Ten minutes prior to NKA challenge the subjects inhaled either thiorphan (2.5 mg/ml, 0.5 ml) or placebo. To detect a possible nonspecific effect of thiorphan, we investigated the effect of the same pretreatment with thiorphan or placebo on the dose-response curve to methacholine in a separate set of experiments. The response was measured by the flow from standardized partial expiratory flow-volume curves (V40p), expressed in percent fall from baseline. NKA log dose-response curves were analyzed using the area under the curve (AUC) and the response to the highest dose of 1,000 micrograms/ml (V40p,1000). The methacholine dose-response curves were characterized by their position (PC40V40p) and the maximal-response plateau (MV40p). Baseline V40p was not affected by either pretreatment (p greater than 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

[Magnetic resonance imaging features in two Chinese family with congenital fibrosis of extraocular muscles].

PubMed

Wu, Li; Zhou, Lian-Hong; Liu, Chang-Sheng; Cha, Yun-Fei; Wang, Jiong; Xing, Yi-Qiao

2009-11-01

The aim of this article was to investigate the structural basis of ocular motility and visual abnormalities in humans with congenital fibrosis of the extraocular muscles (CFEOM). 17 volunteers from 2 CFEOM pedigrees Clinical ophthalmic and motility examed and 18 normal control subjects were correlated with thin-sectioned magnetic resonance imaging (MRI) across the orbit and the brain-stem level. Subjects with CFEOM had severe bilateral blepharoptosis, limited supraduction, and variable ophthalmoplegia. In affected subjects, MRI demonstrated atrophy of the levator palpebrae superioris, all EOMs, and the optic nerves, and small or absent orbital motor nerves. The oculomotor nerve was most severely hypoplastic, but the abducens was also affected. Subjects with CFEOM exhibited subclinical but highly significant reduction from normal in mean optic nerve size (P < 0.05). There are also some difference between the two CFEOM pedigrees. These findings suggest that neuronal disease is primary in CFEOM, with myopathy arising secondary to abnormal innervation and the oculomotor nucleus and trochlear nucleus of the abnormalities defects.

The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study.

PubMed

Zhang, Qiongyue; Miao, Qing; Ye, Hongying; Zhang, Zhaoyun; Zuo, Chuantao; Hua, Fengchun; Guan, Yihui; Li, Yiming

2014-09-01

Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

The Environment and the Microbial Ecology of Human Skin

PubMed Central

McBride, Mollie E.; Duncan, W. Christopher; Knox, J. M.

1977-01-01

Microbial flora of the skin of three human population groups representing different natural environments was examined quantitatively and qualitatively to determine whether environmental differences in temperature and humidity can influence the microbial flora of normal skin. Five anatomical skin sites - hands, back, axillae, groin, and feet - were sampled from 10 subjects working in a high-humidity, high-temperature environment, 10 subjects from a low-temperature, high-humidity environment, and 10 subjects working in a moderate-temperature and low-humidity environment. Bacterial populations were significantly larger from the back, axillae, and feet in individuals from the high-temperature and high-humidity environment as compared to the moderate-temperature, low-humidity environment. High humidity and low temperature had no significant effect on total populations, but this group showed a higher frequency of isolation of fungi, and gram-negative bacteria from the back and feet. Although there was an indication that increase in the environmental humidity could result in an increased frequency of isolation of gram-negative bacteria, there was no evidence that an increase in either temperature or humidity altered the relative proportions of gram-negative bacteria in the predominantly gram-positive microbial flora found on normal skin. It was concluded that, although climatic changes may cause fluctation in microbial populations from certain sites, they are not a major influence on the ecology of the microbial flora of normal skin in the natural environment. The variables introduced by studying individuals in their natural environment and the influence of these on the results are discussed. PMID:16345214

Interaction of brain noradrenergic system and the hypothalamic-pituitary-adrenal (HPA) axis in man.

PubMed

Young, Elizabeth A; Abelson, James L; Cameron, Oliver G

2005-09-01

Numerous interactions between the brainstem locus coeruleus system and the HPA axis have been shown in experimental animals. This relationship is less well characterized in humans and little is known about the influence of psychiatric disorders, which disturb one of these systems, on this relationship. Untreated subjects with pure MDD (n = 13), MDD with comorbid anxiety disorders (n = 17), and pure anxiety disorders (n = 15) were recruited by advertising. Age and sex matched control subjects were recruited for each subject with a psychiatric diagnosis (n = 45). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for ACTH assay. These same subjects also underwent a clonidine challenge study for assessment of growth hormone release as a marker of tonic noradrenergic activation. Examining log transformed area under the curve response for each hormone, a significant negative relationship (simple regression) was observed between systems in normal subjects. This relationship was preserved in anxiety subjects. However, both pure depressed and comorbid depressed and anxiety subjects demonstrated disruption of this relationship. Under normal circumstances, noradrenergic systems can influence the magnitude of the HPA axis response to stress. However, in subjects with major depression, HPA axis activation appears autonomous of noradrenergic influence.

Hyperglycemia may determine fibrinopeptide A plasma level increase in humans.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Marchi, E; Torella, R

1989-12-01

The effects of hyperglycemia on plasma fibrinopeptide A (FPA) levels in normal subjects are reported. An increase of FPA concentration parallel to sustained hyperglycemia was observed; when the glycemia returned to basal values, FPA showed values in normal range. Heparin infusion was able to significantly decrease the hyperglycemia-induced augment of FPA levels. Isovolumic-isotonic NaCl solution infusion produced a slight (NS) increase in FPA levels; however, mild hyperglycemia, achieved by glucagon, was also able to produce a significant increase in FPA concentration. These data demonstrate the direct role of hyperglycemia in conditioning FPA level, and suggest that hyperglycemia, by itself, is a sufficient stimulus to produce thrombin activation in humans.

Modeling Longitudinal Data Containing Non-Normal Within Subject Errors

NASA Technical Reports Server (NTRS)

Feiveson, Alan; Glenn, Nancy L.

2013-01-01

The mission of the National Aeronautics and Space Administration’s (NASA) human research program is to advance safe human spaceflight. This involves conducting experiments, collecting data, and analyzing data. The data are longitudinal and result from a relatively few number of subjects; typically 10 – 20. A longitudinal study refers to an investigation where participant outcomes and possibly treatments are collected at multiple follow-up times. Standard statistical designs such as mean regression with random effects and mixed–effects regression are inadequate for such data because the population is typically not approximately normally distributed. Hence, more advanced data analysis methods are necessary. This research focuses on four such methods for longitudinal data analysis: the recently proposed linear quantile mixed models (lqmm) by Geraci and Bottai (2013), quantile regression, multilevel mixed–effects linear regression, and robust regression. This research also provides computational algorithms for longitudinal data that scientists can directly use for human spaceflight and other longitudinal data applications, then presents statistical evidence that verifies which method is best for specific situations. This advances the study of longitudinal data in a broad range of applications including applications in the sciences, technology, engineering and mathematics fields.

Cardiovascular effects of variations in habitual levels of physical activity

NASA Technical Reports Server (NTRS)

Blomqvist, C. G.; Mitchell, J. H.

1975-01-01

Mechanisms involved in human cardiovascular adaption to stress, particularly adaption to different levels of physical activity are determined along with quantitative noninvasive methods for evaluation of cardiovascular function during stess in normal subjects and in individuals with latent or manifest cardiovascular disease. Results are summarized.

On children's dyslexia with NIRS

NASA Astrophysics Data System (ADS)

Gan, Zhuo; Li, Chengjun; Gong, Hui; Luo, Qingming; Yao, Bin; Song, Ranran; Wu, Hanrong

2003-12-01

Developmental dyslexia is a kind of prevalent psychologic disease. Some functional imaging technologies, such as FMRI and PET, have been used to study the brain activities of dyslexics. NIRS is a kind of novel technology which is more and more widely being used for study of the cognitive psychology. However, there aren"t reports about the dyslexic research using NIRS to be found until now. This paper introduces a NIRS system of four measuring channels. Brain activities of dyslexic subjects and normal subjects during reading task were studied with the NIRS system. Two groups of subjects, the group of dyslexia and the group of normal, were appointed to perform two reading tasks. At the same time, their cortical activities were measured with the NIRS system. This experimental result indicates that the brain activities of the dyslexic group were significantly higher than the control group in BA 48 and that NIRS can be used for the study of human brain activity.

C/EBPα expression is downregulated in human nonmelanoma skin cancers and inactivation of C/EBPα confers susceptibility to UVB-induced skin squamous cell carcinomas.

PubMed

Thompson, Elizabeth A; Zhu, Songyun; Hall, Jonathan R; House, John S; Ranjan, Rakesh; Burr, Jeanne A; He, Yu-Ying; Owens, David M; Smart, Robert C

2011-06-01

Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBPα (CCAAT/enhancer-binding protein-α) in the DNA damage response network, where C/EBPα is induced following UVB DNA damage, regulates the G(1) checkpoint, and diminished or ablated expression of C/EBPα results in G(1) checkpoint failure. In the current study we observed that C/EBPα is induced in normal human epidermal keratinocytes and in the epidermis of human subjects exposed to UVB radiation. The analysis of human skin precancerous and cancerous lesions (47 cases) for C/EBPα expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBPα similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBPα. To determine the significance of C/EBPα in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBPα (CKOα) were exposed to UVB. CKOα mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKOα mice displayed keratinocyte cell cycle checkpoint failure in vivo in response to UVB that was characterized by abnormal entry of keratinocytes into S phase. Our results demonstrate that C/EBPα is silenced in human SCC and loss of C/EBPα confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB.

C/EBPα Expression Is Downregulated in Human Nonmelanoma Skin Cancers and Inactivation of C/EBPα Confers Susceptibility to UVB-Induced Skin Squamous Cell Carcinomas

PubMed Central

Thompson, Elizabeth A.; Zhu, Songyun; Hall, Jonathan R.; House, John S.; Ranjan, Rakesh; Burr, Jeanne A.; He, Yu-Ying; Owens, David M.; Smart, Robert C.

2012-01-01

Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBPα (CCAAT/enhancer-binding protein-α) in the DNA damage response network, where C/EBPα is induced following UVB DNA damage, regulates the G1 checkpoint, and diminished or ablated expression of C/EBPα results in G1 checkpoint failure. In the current study we observed that C/EBPα is induced in normal human epidermal keratinocytes and in the epidermis of human subjects exposed to UVB radiation. The analysis of human skin precancerous and cancerous lesions (47 cases) for C/EBPα expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBPα similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBPα. To determine the significance of C/EBPα in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBPα (CKOα) were exposed to UVB. CKOα mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKOα mice displayed keratinocyte cell cycle checkpoint failure in vivo in response to UVB that was characterized by abnormal entry of keratinocytes into S phase. Our results demonstrate that C/EBPα is silenced in human SCC and loss of C/EBPα confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB. PMID:21346772

Three-dimensional facial recognition using passive long-wavelength infrared polarimetric imaging.

PubMed

Yuffa, Alex J; Gurton, Kristan P; Videen, Gorden

2014-12-20

We use a polarimetric camera to record the Stokes parameters and the degree of linear polarization of long-wavelength infrared radiation emitted by human faces. These Stokes images are combined with Fresnel relations to extract the surface normal at each pixel. Integrating over these surface normals yields a three-dimensional facial image. One major difficulty of this technique is that the normal vectors determined from the polarizations are not unique. We overcome this problem by introducing an additional boundary condition on the subject. The major sources of error in producing inversions are noise in the images caused by scattering of the background signal and the ambiguity in determining the surface normals from the Fresnel coefficients.

The effect of diphenylhydantoin on metabolic and growth hormone changes during and after exercise.

PubMed Central

Chalmers, R J; Johnson, R H

1983-01-01

Metabolic and human growth hormone responses to exercise were investigated in six normal healthy subjects on two occasions with and without an oral dose of diphenylhydantoin (500 mg). Serum diphenylhydantoin concentrations were similar in all subjects and were just below the accepted therapeutic range for epileptic patients. There was no significant difference in blood lactate, pyruvate or glucose concentrations with diphenylhydantoin. Plasma free fatty acids, and blood glycerol and total ketone concentrations were greater after exercise following diphenylhydantoin. Significantly greater concentrations of human growth hormone occurred during exercise with diphenylhydantoin. Further investigation of the mechanisms by which diphenylhydantoin alters lipolysis and human growth hormone release would be of value as these metabolic and hormonal effects could influence exercise tolerance in athletics and other pursuits. PMID:6886706

Appearance is a function of the face.

PubMed

Borah, Gregory L; Rankin, Marlene K

2010-03-01

Increasingly, third-party insurers deny coverage to patients with posttraumatic and congenital facial deformities because these are not seen as "functional." Recent facial transplants have demonstrated that severely deformed patients are willing to undergo potentially life-threatening surgery in search of a normal physiognomy. Scant quantitative research exists that objectively documents appearance as a primary "function" of the face. This study was designed to establish a population-based definition of the functions of the human face, rank importance of the face among various anatomical areas, and determine the risk value the average person places on a normal appearance. Voluntary adult subjects (n = 210) in three states aged 18 to 75 years were recruited using a quota sampling technique. Subjects completed study questionnaires of demography and bias using the Gamble Chance of Death Questionnaire and the Rosenberg Self-Esteem Scale. The face ranked as the most important anatomical area for functional reconstruction. Appearance was the fifth most important function of the face, after breathing, sight, speech, and eating. Normal facial appearance was rated as very important for one to be a functioning member of American society (p = 0.01) by 49 percent. One in seven subjects (13 percent) would accept a 30 to 45 percent risk of death to obtain a "normal" face. Normal appearance is a primary function of the face, based on a large, culturally diverse population sample across the lifespan. Normal appearance ranks above smell and expression as a function. Restoration of facial appearance is ranked the most important anatomical area for repair. Normal facial appearance is very important for one to be a functional member of American society.

[Asu(1,7)E-CT, an analog of eel calcitonin. A comparative study in man with reference to other synthetic calcitonins].

PubMed

Caniggia, A; Nuti, R; Vattimo, A; Galli, M; Turchetti, V; Franci, B; Martorelli, T; Righi, G

1983-04-28

(Asu) E-CT is a deaminodicarba-analog of the synthetic eel-calcitonin (E-CT) that shows specific activity and the potency reasonably high in comparison with that of the most potent natural hormone. The structure of its molecule indicates that the disulphide bond in calcitonins is not essential for the biological activity but only for the maintenance of the specific conformation by forming an intramolecular bridge. The instability of calcitonins should mainly be attributed to the presence of the disulfide bond and (Asu)E-CT proved to be more stable "in vitro" than native calcitonins. The more prolonged hypocalcemic effect of E-CT and its aminosuberic analog (Asu)E-CT has been accounted for to a greater stability of and persistence at the receptor site. (Asu) E-CT has been largely studied in Japan on experimental animals and successfully used in the treatment of hypercalcemia in man. On the contrary investigations on human administration of this analog are very scarce. The present paper reports studies carried out in normal subjects and Paget's disease patients to investigate the effects of (Asu)E-CT in man in comparison with the effects of synthetic human calcitonin (H-CT) and synthetic salmon calcitonin (S-CT). Two different experimental procedures have been used: 1) rapid intravenous injection of (Asu)E-CT (80 MRC. U.) or respectively of H-CT and S-CT (100 MRC. U.) in 15 subjects (7 normals and 8 with Paget's disease); 2) slow 7 days continuous subcutaneous infusion of similar daily amounts of (Asu)E-CT, H-CT and S-CT administered by a microjet pump device in 21 subjects (7 normals and 14 with Paget's disease). The intravenous administration of (Asu)E-CT induced a rapid and persistent decrease in total plasma calcium, ionized calcium and plasma phosphate that was more evident in Paget's disease patients than in normal subjects. No clearly cut differences have been observed with the hypocalcemic and hypophosphatemic effect of H-CT and S-CT administered intravenously; nevertheless the hypocalcemic effect proved to be more persistent in Paget's disease patients treated with (Asu)E-CT. After intravenous infusion of (Asu)E-CT the plasma level of cAMP rose more evidently in pagetic than in normal subjects but the rise was lower than in H-CT and S-CT treated subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Normalized Index of Synergy for Evaluating the Coordination of Motor Commands

PubMed Central

Togo, Shunta; Imamizu, Hiroshi

2015-01-01

Humans perform various motor tasks by coordinating the redundant motor elements in their bodies. The coordination of motor outputs is produced by motor commands, as well properties of the musculoskeletal system. The aim of this study was to dissociate the coordination of motor commands from motor outputs. First, we conducted simulation experiments where the total elbow torque was generated by a model of a simple human right and left elbow with redundant muscles. The results demonstrated that muscle tension with signal-dependent noise formed a coordinated structure of trial-to-trial variability of muscle tension. Therefore, the removal of signal-dependent noise effects was required to evaluate the coordination of motor commands. We proposed a method to evaluate the coordination of motor commands, which removed signal-dependent noise from the measured variability of muscle tension. We used uncontrolled manifold analysis to calculate a normalized index of synergy. Simulation experiments confirmed that the proposed method could appropriately represent the coordinated structure of the variability of motor commands. We also conducted experiments in which subjects performed the same task as in the simulation experiments. The normalized index of synergy revealed that the subjects coordinated their motor commands to achieve the task. Finally, the normalized index of synergy was applied to a motor learning task to determine the utility of the proposed method. We hypothesized that a large part of the change in the coordination of motor outputs through learning was because of changes in motor commands. In a motor learning task, subjects tracked a target trajectory of the total torque. The change in the coordination of muscle tension through learning was dominated by that of motor commands, which supported the hypothesis. We conclude that the normalized index of synergy can be used to evaluate the coordination of motor commands independently from the properties of the musculoskeletal system. PMID:26474043

Sensorimotor integration in human postural control

NASA Technical Reports Server (NTRS)

Peterka, R. J.

2002-01-01

It is generally accepted that human bipedal upright stance is achieved by feedback mechanisms that generate an appropriate corrective torque based on body-sway motion detected primarily by visual, vestibular, and proprioceptive sensory systems. Because orientation information from the various senses is not always available (eyes closed) or accurate (compliant support surface), the postural control system must somehow adjust to maintain stance in a wide variety of environmental conditions. This is the sensorimotor integration problem that we investigated by evoking anterior-posterior (AP) body sway using pseudorandom rotation of the visual surround and/or support surface (amplitudes 0.5-8 degrees ) in both normal subjects and subjects with severe bilateral vestibular loss (VL). AP rotation of body center-of-mass (COM) was measured in response to six conditions offering different combinations of available sensory information. Stimulus-response data were analyzed using spectral analysis to compute transfer functions and coherence functions over a frequency range from 0.017 to 2.23 Hz. Stimulus-response data were quite linear for any given condition and amplitude. However, overall behavior in normal subjects was nonlinear because gain decreased and phase functions sometimes changed with increasing stimulus amplitude. "Sensory channel reweighting" could account for this nonlinear behavior with subjects showing increasing reliance on vestibular cues as stimulus amplitudes increased. VL subjects could not perform this reweighting, and their stimulus-response behavior remained quite linear. Transfer function curve fits based on a simple feedback control model provided estimates of postural stiffness, damping, and feedback time delay. There were only small changes in these parameters with increasing visual stimulus amplitude. However, stiffness increased as much as 60% with increasing support surface amplitude. To maintain postural stability and avoid resonant behavior, an increase in stiffness should be accompanied by a corresponding increase in damping. Increased damping was achieved primarily by decreasing the apparent time delay of feedback control rather than by changing the damping coefficient (i.e., corrective torque related to body-sway velocity). In normal subjects, stiffness and damping were highly correlated with body mass and moment of inertia, with stiffness always about 1/3 larger than necessary to resist the destabilizing torque due to gravity. The stiffness parameter in some VL subjects was larger compared with normal subjects, suggesting that they may use increased stiffness to help compensate for their loss. Overall results show that the simple act of standing quietly depends on a remarkably complex sensorimotor control system.

The serotonin-dopamine interaction measured with positron emission tomography (PET) and C-11 raclopride in normal human subjects

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

Smith, G.S.; Dewey, S.L.; Logan, J.

1994-05-01

Our previous studies have shown that the interaction between serotonin and dopamine can be measured with C-11 raclopride and PET in the baboon brain. A series of studies was undertaken to extend dim findings to the normal human brain. PET studies were conducted in male control subjects (n=8) using the CTI 931 tomograph. Two C-11 raclopride scans were performed, prior to and 180 minutes following administration of the selective serotonin releasing agent, fenfluramine (60mg/PO). The neuroendocrine response to fenfluramine challenge is commonly used in psychiatric research as an index of serotonin activity. The C-11 raclopride data were analyzed with themore » distribution volume method. For the group of subjects, an increase was observed in the striatum to cerebellum ratio (specific to non-specific binding ratio), in excess of the test-retest variability of the ligand. Variability in response was observed across subjects. These results are consistent with our previous findings in the baboon that citalopram administration increased C-11 raclopride binding, consistent with a decrease in endogenous dopamine. In vivo microdialysis studies in freely moving rats confirmed that citalopram produces a time-dependent decrease in extracellular dopamine levels, consistent with the PET results. In vivo PET studies of the serotonin-dopamine interaction are relevant to the evaluation of etiologic and therapeutic mechanisms in schizophrenia and affective disorder.« less

[Motor behavior of human fetuses during the second trimester of gestation: a longitudinal ultrasound study].

PubMed

Reynoso, C; Crespo-Eguílaz, N; Alcázar, J L; Narbona, J

2015-03-01

The aim of this research is to contribute to knowledge of the normal spontaneous motor behavior of the human fetus during the second trimester of pregnancy. This study focuses on five patterns of spontaneous fetal movement: startle (S), axo-rhizomelic rhythmia (ARR), axial stretching (AS), general movement (GM), and diaphragmatic contraction (DC). A cohort of 13 subjects was followed up using 2D obstetrical ultrasound images at 12, 16, 20, and 24 weeks of gestation. As inclusion criteria, neonatal neurological examination and general movements after eutocic delivery at term were normal in all of the subjects, and their neuromotor and cognitive development until the end of pre-school age were also normal. All these five motor patterns are present at the beginning of the 2(nd) gestational trimester, but their quantitative and qualitative traits are diverse according to gestational ages. The phasic, isolated or rhythmically repeated movements, S and ARR, are prominent at 12 and 16 weeks of gestation, and then their presence gradually diminishes. By contrast, tonic and complex AS and GM movements increase their presence and quality at 20 and 24 weeks. RAR constitute a particular periodic motor pattern not described in previous literature. Moreover, the incidence of DC is progressive throughout the trimester, in clusters of 2-6 arrhythmic and irregular beats. Fetal heart rate increases during fetal motor active periods. All five normal behavioral patterns observed in the ultrasounds reflect the progressive tuning of motor generators in human nervous system during mid-pregnancy. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Long-Term Green Tea Supplementation Does Not Change the Human Gut Microbiota

PubMed Central

Janssens, Pilou L. H. R.; Penders, John; Hursel, Rick; Budding, Andries E.; Savelkoul, Paul H. M.; Westerterp-Plantenga, Margriet S.

2016-01-01

Background Green tea catechins may play a role in body weight regulation through interactions with the gut microbiota. Aim We examined whether green tea supplementation for 12 weeks induces changes in composition of the human gut microbiota. Methods 58 Caucasian men and women were included in a randomized, placebo-controlled design. For 12 weeks, subjects consumed either green tea (>0.56 g/d epigallocatechin-gallate + 0.28 ∼ 0.45 g/d caffeine) or placebo capsules. Fecal samples were collected twice (baseline, vs. week 12) for analyses of total bacterial profiles by means of IS-profiling, a 16S-23S interspacer region-based profiling method. Results No significant changes between baseline and week 12 in subjects receiving green tea or placebo capsules, and no significant interactions between treatment (green tea or placebo) and time (baseline and week 12) were observed for body composition. Analysis of the fecal samples in subjects receiving green tea and placebo showed similar bacterial diversity and community structures, indicating there were no significant changes in bacterial diversity between baseline and week 12 in subjects receiving green tea capsules or in subjects receiving placebo capsules. No significant interactions were observed between treatment (green tea or placebo) and time (baseline and week 12) for the gut microbial diversity. Although, there were no significant differences between normal weight and overweight subjects in response to green tea, we did observe a reduced bacterial alpha diversity in overweight as compared to normal weight subjects (p = 0.002). Conclusion Green tea supplementation for 12 weeks did not have a significant effect on composition of the gut microbiota. Trial Registration ClinicalTrials.gov NCT01556321 PMID:27054321

Human-Computer Interactions: Are There Adverse Health Consequences?

ERIC Educational Resources Information Center

Emurian, Henry H.

1989-01-01

Discusses the hypothesis that similarities may exist between laboratory research paradigms evoking elevated blood pressure during task performance by normal subjects and video display terminal (VDT) work done by data clerks and college students. Type A behavior and the development of coronary heart disease are discussed, and further research needs…

Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep.

PubMed

Huupponen, E; Maksimow, A; Lapinlampi, P; Särkelä, M; Saastamoinen, A; Snapir, A; Scheinin, H; Scheinin, M; Meriläinen, P; Himanen, S-L; Jääskeläinen, S

2008-02-01

Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, induces a unique, sleep-like state of sedation. The objective of the present work was to study human electroencephalogram (EEG) sleep spindles during dexmedetomidine sedation and compare them with spindles during normal physiological sleep, to test the hypothesis that dexmedetomidine exerts its effects via normal sleep-promoting pathways. EEG was continuously recorded from a bipolar frontopolar-laterofrontal derivation with Entropy Module (GE Healthcare) during light and deep dexmedetomidine sedation (target-controlled infusions set at 0.5 and 3.2 ng/ml) in 11 healthy subjects, and during physiological sleep in 10 healthy control subjects. Sleep spindles were visually scored and quantitatively analyzed for density, duration, amplitude (band-pass filtering) and frequency content (matching pursuit approach), and compared between the two groups. In visual analysis, EEG activity during dexmedetomidine sedation was similar to physiological stage 2 (S2) sleep with slight to moderate amount of slow-wave activity and abundant sleep spindle activity. In quantitative EEG analyses, sleep spindles were similar during dexmedetomidine sedation and normal sleep. No statistically significant differences were found in spindle density, amplitude or frequency content, but the spindles during dexmedetomidine sedation had longer duration (mean 1.11 s, SD 0.14 s) than spindles in normal sleep (mean 0.88 s, SD 0.14 s; P=0.0014). Analysis of sleep spindles shows that dexmedetomidine produces a state closely resembling physiological S2 sleep in humans, which gives further support to earlier experimental evidence for activation of normal non-rapid eye movement sleep-promoting pathways by this sedative agent.

Subject-Specific Sparse Dictionary Learning for Atlas-Based Brain MRI Segmentation.

PubMed

Roy, Snehashis; He, Qing; Sweeney, Elizabeth; Carass, Aaron; Reich, Daniel S; Prince, Jerry L; Pham, Dzung L

2015-09-01

Quantitative measurements from segmentations of human brain magnetic resonance (MR) images provide important biomarkers for normal aging and disease progression. In this paper, we propose a patch-based tissue classification method from MR images that uses a sparse dictionary learning approach and atlas priors. Training data for the method consists of an atlas MR image, prior information maps depicting where different tissues are expected to be located, and a hard segmentation. Unlike most atlas-based classification methods that require deformable registration of the atlas priors to the subject, only affine registration is required between the subject and training atlas. A subject-specific patch dictionary is created by learning relevant patches from the atlas. Then the subject patches are modeled as sparse combinations of learned atlas patches leading to tissue memberships at each voxel. The combination of prior information in an example-based framework enables us to distinguish tissues having similar intensities but different spatial locations. We demonstrate the efficacy of the approach on the application of whole-brain tissue segmentation in subjects with healthy anatomy and normal pressure hydrocephalus, as well as lesion segmentation in multiple sclerosis patients. For each application, quantitative comparisons are made against publicly available state-of-the art approaches.

Cortisol as a Biomarker of Stress in Term Human Labor: Physiological and Methodological Issues

PubMed Central

Newton, Edward R.; Tanner, Charles J.; Heitkemper, Margaret M.

2013-01-01

Literature on the use of plasma cortisol to quantify psychophysiological stress in humans is extensive. However, in parturition at term gestation the use of cortisol as a biomarker of stress is particularly complex. Plasma cortisol levels increase as labor progresses. This increase seems to be important for maintenance of maternal/fetal wellbeing and facilitation of normal labor progress. Unique physiological and methodological issues involved in the use of cortisol as a biomarker of stress in labor present challenges for researchers. This review examines these issues, suggests mixed methods and within-subject repeated measures designs, and offers recommendations for assay procedures for parturient sampling. Documentation of clinical interventions and delivery outcomes may elucidate relationships among psychophysiological stressors, cortisol and normal labor progress. With attention to these methodological issues, analysis of plasma cortisol may lead to clinical interventions that support normal labor physiology. PMID:23338011

Understanding the complexity of human gait dynamics

NASA Astrophysics Data System (ADS)

Scafetta, Nicola; Marchi, Damiano; West, Bruce J.

2009-06-01

Time series of human gait stride intervals exhibit fractal and multifractal properties under several conditions. Records from subjects walking at normal, slow, and fast pace speed are analyzed to determine changes in the fractal scalings as a function of the stress condition of the system. Records from subjects with different age from children to elderly and patients suffering from neurodegenerative disease are analyzed to determine changes in the fractal scalings as a function of the physical maturation or degeneration of the system. A supercentral pattern generator model is presented to simulate the above two properties that are typically found in dynamical network performance: that is, how a dynamical network responds to stress and to evolution.

Differential effects of mental stress on plasma homovanillic acid in schizophrenia and normal controls.

PubMed

Sumiyoshi, T; Saitoh, O; Yotsutsuji, T; Itoh, H; Kurokawa, K; Kurachi, M

1999-04-01

We previously reported that mental stress by Kraepelin's arithmetic test decreases plasma homovanillic acid (pHVA) levels in psychiatrically normal healthy human subjects. The present study was undertaken to determine whether this pattern of changes in pHVA concentrations resulting from mental stress is altered in patients with schizophrenia. Fourteen male patients with schizophrenia including those under ongoing neuroleptic treatment and 14 normal male volunteers participated in the study. Following overnight fast and restricted physical activity, the subjects performed Kraepelin's arithmetic test for 30 minutes. Plasma samples were collected immediately before and after the test for measurement of pHVA levels. A significant diagnosis by Kraepelin's test effect was observed due to a decrease in pHVA levels by the Kraepelin test in control subjects but not in patients with schizophrenia. Changes in pHVA levels during the Kraepelin test positively correlated with pre-test pHVA levels in control subjects, while this correlation was not observed in patients with schizophrenia. These results may be further support for the presence of a dopamine-dependent restitutive system in the brain. The absence of response of pHVA levels to mental stress in patients with schizophrenia may indicate that the dopamine restitutive system in these patients is disrupted or already down-regulated, as previously predicted.

48-h Glucose infusion in humans: effect on hormonal responses, hunger and food intake

PubMed Central

Teff, Karen L.; Petrova, Maja; Havel, Peter J.; Townsend, Raymond R.

2009-01-01

Experimentally-induced hyperglycemia by prolonged glucose infusion allows investigation of the effects of sustained stimulation of the pancreatic β-cell on insulin secretion and sensitivity. Hormonal responses to a meal following prolonged glucose infusions have not been investigated. To determine if a 48-h glucose infusion alters hormonal responses to a test meal as well as food intake and hunger in normal weight individuals, 16 subjects (8 men, 8 women, age 18–30 y, mean BMI=21.7±1.6 kg/m2) were infused for 48-h with either saline (50 ml/h) or 15% glucose (200 mg/m2/min). Subjects ingested a 600 kcal mixed nutrient meal 3-h after infusion termination. Blood samples were taken during the 48-h and for 4 hours following food ingestion. The 48-h glucose infusion elicited a metabolic profile of a glucose intolerant obese subjects, with increased plasma glucose, insulin and leptin (all P<0.01) and increased HOMA-IR (P<0.001). During meal ingestion, early insulin secretion was increased (P<0.05) but postprandial glucose (P<0.01) and insulin (P<0.01) excursions were lower following the glucose infusion. Postprandial plasma triglyceride concentrations were increased after glucose compared with saline. Food intake and hunger ratings were not different between the two conditions. Plasma leptin levels were inversely correlated with hunger (P<0.03) in both conditions and with food intake (P<0.003) during the glucose condition only. Thus, a 48-h glucose infusion does not impair postprandial hormonal responses, alter food intake or hunger in normal weight subjects. The glucose-induced increases in plasma leptin result in a stronger inverse relationship between plasma leptin and hunger as well as food intake. These data are the first to demonstrate a relationship between leptin and hunger in normal weight, non-calorically restricted human subjects. PMID:17275862

In vivo Raman spectroscopy of human uterine cervix: exploring the utility of vagina as an internal control

NASA Astrophysics Data System (ADS)

Shaikh, Rubina; Dora, Tapas Kumar; Chopra, Supriya; Maheshwari, Amita; Kedar K., Deodhar; Bharat, Rekhi; Krishna, C. Murali

2014-08-01

In vivo Raman spectroscopy is being projected as a new, noninvasive method for cervical cancer diagnosis. In most of the reported studies, normal areas in the cancerous cervix were used as control. However, in the Indian subcontinent, the majority of cervical cancers are detected at advanced stages, leaving no normal sites for acquiring control spectra. Moreover, vagina and ectocervix are reported to have similar biochemical composition. Thus, in the present study, we have evaluated the feasibility of classifying normal and cancerous conditions in the Indian population and we have also explored the utility of the vagina as an internal control. A total of 228 normal and 181 tumor in vivo Raman spectra were acquired from 93 subjects under clinical supervision. The spectral features in normal conditions suggest the presence of collagen, while DNA and noncollagenous proteins were abundant in tumors. Principal-component linear discriminant analysis (PC-LDA) yielded 97% classification efficiency between normal and tumor groups. An analysis of a normal cervix and vaginal controls of cancerous and noncancerous subjects suggests similar spectral features between these groups. PC-LDA of tumor, normal cervix, and vaginal controls further support the utility of the vagina as an internal control. Overall, findings of the study corroborate with earlier studies and facilitate objective, noninvasive, and rapid Raman spectroscopic-based screening/diagnosis of cervical cancers.

In vivo Raman spectroscopy of human uterine cervix: exploring the utility of vagina as an internal control.

PubMed

Shaikh, Rubina; Dora, Tapas Kumar; Chopra, Supriya; Maheshwari, Amita; Kedar K, Deodhar; Bharat, Rekhi; Krishna, C Murali

2014-08-01

In vivo Raman spectroscopy is being projected as a new, noninvasive method for cervical cancer diagnosis. In most of the reported studies, normal areas in the cancerous cervix were used as control. However, in the Indian subcontinent, the majority of cervical cancers are detected at advanced stages, leaving no normal sites for acquiring control spectra. Moreover, vagina and ectocervix are reported to have similar biochemical composition. Thus, in the present study, we have evaluated the feasibility of classifying normal and cancerous conditions in the Indian population and we have also explored the utility of the vagina as an internal control. A total of 228 normal and 181 tumor in vivo Raman spectra were acquired from 93 subjects under clinical supervision. The spectral features in normal conditions suggest the presence of collagen, while DNA and noncollagenous proteins were abundant in tumors. Principal-component linear discriminant analysis (PC-LDA) yielded 97% classification efficiency between normal and tumor groups. An analysis of a normal cervix and vaginal controls of cancerous and noncancerous subjects suggests similar spectral features between these groups. PC-LDA of tumor, normal cervix, and vaginal controls further support the utility of the vagina as an internal control. Overall, findings of the study corroborate with earlier studies and facilitate objective, noninvasive, and rapid Raman spectroscopic-based screening/diagnosis of cervical cancers.

Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Lefebvre, P J

1991-12-01

1. In this study an acute anti-hypertensive effect of three anti-oxidant agents (vitamin C, thiopronine and glutathione) in hypertensive subjects and in both hypertensive and non-hypertensive diabetic patients is reported. 2. The anti-oxidants had no effect on blood pressure in healthy normal subjects at a dose of 6 mmol, but thiopronine and glutathione produced a significant hypotensive effect at a dose of 12 mmol. 3. These data suggest that anti-oxidants might have a dilatatory effect and that an imbalance of the nitric oxide-free radical interaction might facilitate the development of hypertension in humans.

Extracts from black carrot tissue culture as potent anticancer agents.

PubMed

Sevimli-Gur, Canan; Cetin, Burcu; Akay, Seref; Gulce-Iz, Sultan; Yesil-Celiktas, Ozlem

2013-09-01

Black carrots contain anthocyanins possessing enhanced physiological activities. Explants of young black carrot shoots were cultured in Murashige and Skoog (MS) medium for callus initiation and were transferred to new MS medium supplemented with four different combinations of 2,4-dichlorophenoxyacetic acid and kinetin. Subsequently, the lyophilized calli and black carrot harvested from fields were subjected to ultrasound extraction with ethanol at a ratio of 1:15 (w:v). Obtained extracts were applied to various human cancer cell lines including MCF-7 SK-BR-3 and MDA-MB-231 (human breast adenocarcinomas), HT-29 (human colon adenocarcinoma), PC-3 (human prostate adenocarcinoma), Neuro 2A (Musmusculus neuroblastoma) cancer cell lines and VERO (African green monkey kidney) normal cell line by MTT assay. The highest cytotoxic activity was achieved against Neuro-2A cell lines exhibiting viability of 38-46% at 6.25 μg/ml concentration for all calli and natural extracts. However, a significantly high IC50 value of 170.13 μg/ml was attained in normal cell line VERO indicating that its natural counterpart is an ideal candidate for treatment of brain cancer without causing negative effects to normal healthy cells.

Multiscale entropy analysis of human gait dynamics

NASA Astrophysics Data System (ADS)

Costa, M.; Peng, C.-K.; L. Goldberger, Ary; Hausdorff, Jeffrey M.

2003-12-01

We compare the complexity of human gait time series from healthy subjects under different conditions. Using the recently developed multiscale entropy algorithm, which provides a way to measure complexity over a range of scales, we observe that normal spontaneous walking has the highest complexity when compared to slow and fast walking and also to walking paced by a metronome. These findings have implications for modeling locomotor control and for quantifying gait dynamics in physiologic and pathologic states.

The SRI24 multichannel brain atlas: construction and applications

NASA Astrophysics Data System (ADS)

Rohlfing, Torsten; Zahr, Natalie M.; Sullivan, Edith V.; Pfefferbaum, Adolf

2008-03-01

We present a new standard atlas of the human brain based on magnetic resonance images. The atlas was generated using unbiased population registration from high-resolution images obtained by multichannel-coil acquisition at 3T in a group of 24 normal subjects. The final atlas comprises three anatomical channels (T I-weighted, early and late spin echo), three diffusion-related channels (fractional anisotropy, mean diffusivity, diffusion-weighted image), and three tissue probability maps (CSF, gray matter, white matter). The atlas is dynamic in that it is implicitly represented by nonrigid transformations between the 24 subject images, as well as distortion-correction alignments between the image channels in each subject. The atlas can, therefore, be generated at essentially arbitrary image resolutions and orientations (e.g., AC/PC aligned), without compounding interpolation artifacts. We demonstrate in this paper two different applications of the atlas: (a) region definition by label propagation in a fiber tracking study is enabled by the increased sharpness of our atlas compared with other available atlases, and (b) spatial normalization is enabled by its average shape property. In summary, our atlas has unique features and will be made available to the scientific community as a resource and reference system for future imaging-based studies of the human brain.

In vivo traffic of indium-111-oxine labeled human lymphocytes collected by automated apheresis

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

Read, E.J.; Keenan, A.M.; Carter, C.S.

1990-06-01

The in vivo traffic patterns of autologous lymphocytes were studied in five normal human volunteers using lymphocytes obtained by automated apheresis, separated on Ficoll-Hypaque gradients, and labeled ex vivo with {sup 111}In-oxine. Final lymphocyte infusions contained 1.8-3.1 X 10(9) cells and 270-390 microCi (9.99-14.43 MBq) {sup 111}In, or 11-17 microCi (0.41-0.63 MBq) per 10(8) lymphocytes. Gamma imaging showed transient lung uptake and significant retention of radioactivity in the liver and spleen. Progressive uptake of activity in normal, nonpalpable axillary and inguinal lymph nodes was seen from 24 to 96 hr. Accumulation of radioactivity also was demonstrated at the forearm skinmore » test site, as well as in its associated epitrochlear and axillary lymph nodes, in a subject who had been tested for delayed hypersensitivity with tetanus toxoid. Indium-111-oxine labeled human lymphocytes may provide a useful tool for future studies of normal and abnormal lymphocyte traffic.« less

A brain imaging repository of normal structural MRI across the life course: Brain Images of Normal Subjects (BRAINS).

PubMed

Job, Dominic E; Dickie, David Alexander; Rodriguez, David; Robson, Andrew; Danso, Sammy; Pernet, Cyril; Bastin, Mark E; Boardman, James P; Murray, Alison D; Ahearn, Trevor; Waiter, Gordon D; Staff, Roger T; Deary, Ian J; Shenkin, Susan D; Wardlaw, Joanna M

2017-01-01

The Brain Images of Normal Subjects (BRAINS) Imagebank (http://www.brainsimagebank.ac.uk) is an integrated repository project hosted by the University of Edinburgh and sponsored by the Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) collaborators. BRAINS provide sharing and archiving of detailed normal human brain imaging and relevant phenotypic data already collected in studies of healthy volunteers across the life-course. It particularly focusses on the extremes of age (currently older age, and in future perinatal) where variability is largest, and which are under-represented in existing databanks. BRAINS is a living imagebank where new data will be added when available. Currently BRAINS contains data from 808 healthy volunteers, from 15 to 81years of age, from 7 projects in 3 centres. Additional completed and ongoing studies of normal individuals from 1st to 10th decades are in preparation and will be included as they become available. BRAINS holds several MRI structural sequences, including T1, T2, T2* and fluid attenuated inversion recovery (FLAIR), available in DICOM (http://dicom.nema.org/); in future Diffusion Tensor Imaging (DTI) will be added where available. Images are linked to a wide range of 'textual data', such as age, medical history, physiological measures (e.g. blood pressure), medication use, cognitive ability, and perinatal information for pre/post-natal subjects. The imagebank can be searched to include or exclude ranges of these variables to create better estimates of 'what is normal' at different ages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Serum thymulin in human zinc deficiency.

PubMed Central

Prasad, A S; Meftah, S; Abdallah, J; Kaplan, J; Brewer, G J; Bach, J F; Dardenne, M

1988-01-01

The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions. Images PMID:3262625

Core body temperature in obesity.

PubMed

Heikens, Marc J; Gorbach, Alexander M; Eden, Henry S; Savastano, David M; Chen, Kong Y; Skarulis, Monica C; Yanovski, Jack A

2011-05-01

A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity. We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals. In study 1, nonobese [body mass index (BMI; in kg/m(2)) <30] and obese (BMI ≥30) adults swallowed wireless core temperature-sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18-25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for ≥48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis. Mean (±SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 ± 0.03°C compared with 36.89 ± 0.03°C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature ≈0.23°C greater than that of men (36.99 ± 0.03°C compared with 36.76 ± 0.03°C; P < 0.0001). Obesity is not generally associated with a reduced core body temperature. It may be necessary to study individuals with function-altering mutations in core temperature-regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500.

Core body temperature in obesity123

PubMed Central

Heikens, Marc J; Gorbach, Alexander M; Eden, Henry S; Savastano, David M; Chen, Kong Y; Skarulis, Monica C

2011-01-01

Background: A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity. Objective: We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals. Design: In study 1, nonobese [body mass index (BMI; in kg/m2) <30] and obese (BMI ≥30) adults swallowed wireless core temperature–sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18–25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for ≥48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis. Results: Mean (±SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 ± 0.03°C compared with 36.89 ± 0.03°C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature ≈0.23°C greater than that of men (36.99 ± 0.03°C compared with 36.76 ± 0.03°C; P < 0.0001). Conclusions: Obesity is not generally associated with a reduced core body temperature. It may be necessary to study individuals with function-altering mutations in core temperature–regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500. PMID:21367952

Histogram-based normalization technique on human brain magnetic resonance images from different acquisitions.

PubMed

Sun, Xiaofei; Shi, Lin; Luo, Yishan; Yang, Wei; Li, Hongpeng; Liang, Peipeng; Li, Kuncheng; Mok, Vincent C T; Chu, Winnie C W; Wang, Defeng

2015-07-28

Intensity normalization is an important preprocessing step in brain magnetic resonance image (MRI) analysis. During MR image acquisition, different scanners or parameters would be used for scanning different subjects or the same subject at a different time, which may result in large intensity variations. This intensity variation will greatly undermine the performance of subsequent MRI processing and population analysis, such as image registration, segmentation, and tissue volume measurement. In this work, we proposed a new histogram normalization method to reduce the intensity variation between MRIs obtained from different acquisitions. In our experiment, we scanned each subject twice on two different scanners using different imaging parameters. With noise estimation, the image with lower noise level was determined and treated as the high-quality reference image. Then the histogram of the low-quality image was normalized to the histogram of the high-quality image. The normalization algorithm includes two main steps: (1) intensity scaling (IS), where, for the high-quality reference image, the intensities of the image are first rescaled to a range between the low intensity region (LIR) value and the high intensity region (HIR) value; and (2) histogram normalization (HN),where the histogram of low-quality image as input image is stretched to match the histogram of the reference image, so that the intensity range in the normalized image will also lie between LIR and HIR. We performed three sets of experiments to evaluate the proposed method, i.e., image registration, segmentation, and tissue volume measurement, and compared this with the existing intensity normalization method. It is then possible to validate that our histogram normalization framework can achieve better results in all the experiments. It is also demonstrated that the brain template with normalization preprocessing is of higher quality than the template with no normalization processing. We have proposed a histogram-based MRI intensity normalization method. The method can normalize scans which were acquired on different MRI units. We have validated that the method can greatly improve the image analysis performance. Furthermore, it is demonstrated that with the help of our normalization method, we can create a higher quality Chinese brain template.

Measurement of glutathione S-transferase and its class-pi in plasma and tissue biopsies obtained after laparoscopy and endoscopy from subjects with esophagus and gastric cancer.

PubMed

Mohammadzadeh, G S; Nasseri Moghadam, S; Rasaee, M J; Zaree, A B; Mahmoodzadeh, H; Allameh, A

2003-06-01

To develop an indirect enzyme-linked immunosorbent assay (ELISA) for measuring class-pi glutathione S-transferase (GST) in plasma, and tissue biopsies obtained from upper gastrointestinal cancer (UGI Ca) patients. GST activity and GST-pi concentration were detected in normal human squamous esophageal epithelium, normal gastric cardia and their corresponding malignant tumor biopsies. Plasma GST was significantly higher (p < 0.05) in UGI Ca patients as compared to those obtained from normal individuals. Plasma GST-pi concentration in normal subjects was 6.6 +/- 1.9 ng/mg protein, whereas it was higher in UGI Ca patients (esophageal, 10.0 +/- 1.8; gastric, 10.7 +/- 1.7 ng/mL, p

Development of Software for Automatic Analysis of Intervention in the Field of Homeopathy.

PubMed

Jain, Rajesh Kumar; Goyal, Shagun; Bhat, Sushma N; Rao, Srinath; Sakthidharan, Vivek; Kumar, Prasanna; Sajan, Kannanaikal Rappayi; Jindal, Sameer Kumar; Jindal, Ghanshyam D

2018-05-01

To study the effect of homeopathic medicines (in higher potencies) in normal subjects, Peripheral Pulse Analyzer (PPA) has been used to record physiologic variability parameters before and after administration of the medicine/placebo in 210 normal subjects. Data have been acquired in seven rounds; placebo was administered in rounds 1 and 2 and medicine in potencies 6, 30, 200, 1 M, and 10 M was administered in rounds 3 to 7, respectively. Five different medicines in the said potencies were given to a group of around 40 subjects each. Although processing of data required human intervention, a software application has been developed to analyze the processed data and detect the response to eliminate the undue delay as well as human bias in subjective analysis. This utility named Automatic Analysis of Intervention in the Field of Homeopathy is run on the processed PPA data and the outcome has been compared with the manual analysis. The application software uses adaptive threshold based on statistics for detecting responses in contrast to fixed threshold used in manual analysis. The automatic analysis has detected 12.96% higher responses than subjective analysis. Higher response rates have been manually verified to be true positive. This indicates robustness of the application software. The automatic analysis software was run on another set of pulse harmonic parameters derived from the same data set to study cardiovascular susceptibility and 385 responses were detected in contrast to 272 of variability parameters. It was observed that 65% of the subjects, eliciting response, were common. This not only validates the software utility for giving consistent yield but also reveals the certainty of the response. This development may lead to electronic proving of homeopathic medicines (e-proving).

Abnormal Facial Emotion Recognition in Depression: Serial Testing in an Ultra-Rapid-Cycling Patient.

ERIC Educational Resources Information Center

George, Mark S.; Huggins, Teresa; McDermut, Wilson; Parekh, Priti I.; Rubinow, David; Post, Robert M.

1998-01-01

Mood disorder subjects have a selective deficit in recognizing human facial emotion. Whether the facial emotion recognition errors persist during normal mood states (i.e., are state vs. trait dependent) was studied in one male bipolar II patient. Results of five sessions are presented and discussed. (Author/EMK)

EFFECTS OF PREDNISOLONE AND TRIAMCINOLONE ON CORTICOSTEROID LEVELS IN PAROTID FLUID, SERUM, AND URINE.

DTIC Science & Technology

A simultaneous determination was made of 17-OHCS in serum, urine, and parotid fluid, by the Porter-Silber reaction, after the oral administration of...prednisolone, triamcinolone, or placebo to 240 normal human subjects. The data clearly demonstrate the homology of serum and parotid fluid 17-OHCS

REGIONAL DEPOSITION DOSE OF INHALED NANO-SIZE PARTICLES IN HUMAN LUNGS DURING CONTROLLED NORMAL BREATHING

EPA Science Inventory

INTRODUCTION

One of the key factors for affecting respiratory

deposition of particles is the breathing pattern of

individual subjects. Although idealized breathing

patterns (square or sine wave form) are frequently used

for studying lung deposit...

Performance of Junctional Tourniquets in Normal Human Volunteers

DTIC Science & Technology

2014-12-01

cross-hatch marks, and the left side was the zero point that anchored the line. The subject made a cross mark on the line, which went from the left...the ankle . The AAJT, which aims to compress the distal aorta and adjacent blood vessels when used over the umbilicus where there appears to be no

Unprocessed real-time imaging of vitreoretinal surgical maneuvers using a microscope-integrated spectral-domain optical coherence tomography system.

PubMed

Hahn, Paul; Migacz, Justin; O'Connell, Rachelle; Izatt, Joseph A; Toth, Cynthia A

2013-01-01

We have recently developed a microscope-integrated spectral-domain optical coherence tomography (MIOCT) device towards intrasurgical cross-sectional imaging of surgical maneuvers. In this report, we explore the capability of MIOCT to acquire real-time video imaging of vitreoretinal surgical maneuvers without post-processing modifications. Standard 3-port vitrectomy was performed in human during scheduled surgery as well as in cadaveric porcine eyes. MIOCT imaging of human subjects was performed in healthy normal volunteers and intraoperatively at a normal pause immediately following surgical manipulations, under an Institutional Review Board-approved protocol, with informed consent from all subjects. Video MIOCT imaging of live surgical manipulations was performed in cadaveric porcine eyes by carefully aligning B-scans with instrument orientation and movement. Inverted imaging was performed by lengthening of the reference arm to a position beyond the choroid. Unprocessed MIOCT imaging was successfully obtained in healthy human volunteers and in human patients undergoing surgery, with visualization of post-surgical changes in unprocessed single B-scans. Real-time, unprocessed MIOCT video imaging was successfully obtained in cadaveric porcine eyes during brushing of the retina with the Tano scraper, peeling of superficial retinal tissue with intraocular forceps, and separation of the posterior hyaloid face. Real-time inverted imaging enabled imaging without complex conjugate artifacts. MIOCT is capable of unprocessed imaging of the macula in human patients undergoing surgery and of unprocessed, real-time, video imaging of surgical maneuvers in model eyes. These capabilities represent an important step towards development of MIOCT for efficient, real-time imaging of manipulations during human surgery.

Cardiovascular Adjustments to Gravitational Stress

NASA Technical Reports Server (NTRS)

Blomqvist, C. Gunnar; Stone, H. Lowell

1991-01-01

The effects of gravity on the cardiovascular system must be taken into account whenever a hemodynamic assessment is made. All intravascular pressure have a gravity-dependent hydrostatic component. The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn this distribution largely determines cardiac pump function. Multiple control mechanisms are activated to preserve optimal tissue perfusion when the magnitude of the gravitational field or its direction relative to the body changes. Humans are particularly sensitive to such changes because of the combination of their normally erect posture and the large body mass and blood volume below the level of the heart. Current aerospace technology also exposes human subjects to extreme variations in the gravitational forces that range from zero during space travel to as much an nine-times normal during operation of high-performance military aircraft. This chapter therefore emphasizes human physiology.

Partial recovery of hemiparesis following hemispherectomy in infant monkeys.

PubMed

Burke, Mark W; Zangenehpour, Shahin; Ptito, Maurice

2010-01-22

Hemiparesis, unilateral weakness or partial paralysis, is a common outcome following hemispherectomy in humans. We use the non-human primate as an invaluable translational model for our understanding of developmental plasticity in response to hemispherectomy. Three infant vervet monkeys (Chlorocebus sabeus) underwent hemispherectomy at a median age of 9 weeks and two additional monkeys at 48 months. Gross motor assessment was conducted in a large open field that contained a horizontal bar spanning the width of the cage. Subjects were assessed yearly following surgery in infantile lesions for a period of 3 years. Adult-lesioned subjects were assessed 40 months following surgery. Shortly after surgery both infant and adult-lesioned subjects were unable to move the contralateral side of their body, but all subjects were able to walk within 6 months following surgery. At each time point the lower limb gait was normal in infant-lesioned subjects with no apparent limp or dragging, however the upper limb demonstrated significant impairment. Horizontal bar crossing was significantly impaired during the first 24 months following surgery. Adult-lesioned subjects also displayed upper limb movement impairments similar to infant-lesioned subjects. In addition the adult-lesioned subjects displayed a noticeable lower limb limp, which was not observed in the infant-lesioned group. Both groups at each time point showed a propensity for ipsiversive turning. The upper limb gait impairment and horizontal bar crossing of lesioned subjects are reminiscent of hemiparesis seen in hemisperectomized humans with the young-lesioned subjects showing a greater propensity for recovery. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Long latency postural responses are functionally modified by cognitive set.

PubMed

Beckley, D J; Bloem, B R; Remler, M P; Roos, R A; Van Dijk, J G

1991-10-01

We examined how cognitive set influences the long latency components of normal postural responses in the legs. We disturbed the postural stability of standing human subjects with sudden toe-up ankle rotations. To influence the subjects' cognitive set, we varied the rotation amplitude either predictably (serial 4 degrees versus serial 10 degrees) or unpredictably (random mixture of 4 degrees and 10 degrees). The subjects' responses to these ankle rotations were assessed from the EMG activity of the tibialis anterior, the medial gastrocnemius, and the vastus lateralis muscles of the left leg. The results indicate that, when the rotation amplitude is predictable, only the amplitude of the long latency (LL) response in tibialis anterior and vastus lateralis varied directly with perturbation size. Furthermore, when the rotation amplitude is unpredictable, the central nervous system selects a default amplitude for the LL response in the tibialis anterior. When normal subjects are exposed to 2 perturbation amplitudes which include the potential risk of falling, the default LL response in tibialis anterior appropriately anticipates the larger amplitude perturbation rather than the smaller or an intermediate one.

STUDIES ON STRUCTURAL UNITS OF THE γ-GLOBULINS

PubMed Central

Edelman, G. M.; Poulik, M. D.

1961-01-01

When human and rabbit 7S γ-globulins were reduced in strong urea solutions by a number of procedures, their molecular weights fell to approximately ⅓ of the original values. Partial separation of the reduction products was achieved using chromatography and starch gel electrophoresis in urea solutions. One of the components of reduced human 7S γ-globulin was isolated by chromatography, identified by starch gel electrophoresis, and subjected to amino acid analyses. The amino acid composition of this component differed from that of the starting material and also from that of the remaining components. A reduced pathological macroglobulin dissociated to components with an average molecular weight of 41,000. Several reduced human myeloma proteins, when subjected to starch gel electrophoresis, yielded individual patterns that nevertheless had features in common with those of reduced normal γ-globulins. Reduction of normal and abnormal γ-globulins was accompanied by the appearance of titratable sulfhydryl groups. Chemical treatments other than reduction were used to determine the type of bond holding the subunits together. It was tentatively concluded that they were linked by disulfide bonds. An hypothesis is presented to relate the structural features of the various γ-globulins in terms of the multiplicity of polypeptide chains in these molecules. PMID:13725659

Prostacyclins have no direct inotropic effect on isolated atrial strips from the normal and pressure-overloaded human right heart.

PubMed

Holmboe, Sarah; Andersen, Asger; Jensen, Rebekka V; Kimose, Hans Henrik; Ilkjær, Lars B; Shen, Lei; Clapp, Lucie H; Nielsen-Kudsk, Jens Erik

2017-01-01

Prostacyclins are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostacyclins on right heart function are still not clarified. The aim of this study was to investigate the possible direct inotropic properties of clinical available prostacyclin mimetics in the normal and the pressure-overloaded human right atrium. Trabeculae from the right atrium were collected during surgery from chronic thromboembolic pulmonary hypertension (CTEPH) patients with pressure-overloaded right hearts, undergoing pulmonary thromboendarterectomy (n = 10) and from patients with normal right hearts operated by valve replacement or coronary bypass surgery (n = 9). The trabeculae were placed in an organ bath, continuously paced at 1 Hz. They were subjected to increasing concentrations of iloprost, treprostinil, epoprostenol, or MRE-269, followed by isoprenaline to elicit a reference inotropic response. The force of contraction was measured continuously. The expression of prostanoid receptors was explored through quantitative polymerase chain reaction (qPCR). Iloprost, treprostinil, epoprostenol, or MRE-269 did not alter force of contraction in any of the trabeculae. Isoprenaline showed a direct inotropic response in both trabeculae from the pressure-overloaded right atrium and from the normal right atrium. Control experiments on ventricular trabeculae from the pig failed to show an inotropic response to the prostacyclin mimetics. qPCR demonstrated varying expression of the different prostanoid receptors in the human atrium. In conclusion, prostacyclin mimetics did not increase the force of contraction of human atrial trabeculae from the normal or the pressure-overloaded right heart. These data suggest that prostacyclin mimetics have no direct inotropic effects in the human right atrium.

Ocular counterrolling measured during eight hours of sustained body tilt

NASA Technical Reports Server (NTRS)

Miller, E. F., II; Graybiel, A.

1972-01-01

Adaptation of otolith organ activity was investigated by monitoring the ocular counterrolling response of four normal individuals and three persons with severe bilateral loss of labyrinthine function. Several eye photographs were recorded every 30 minutes during a period of 8 hours in which the subject was held in a lateral tilt (60 deg) position. The recorded eye roll position varied to an expected small extent within each test session; this variation about a given mean roll position was similar among the test sessions for all subjects. The mean roll position, on the other hand, changed from session to session in substantial amounts, but these changes appeared to be random with respect to time and among subjects. Furthermore, the intersessional variation in the mean torsional eye position of the normal subjects was equivalent to that of the labyrinthine-defective subjects who displayed little or no counterrolling. These results suggest that the human counterrolling response is maintained either by essentially nonadapting macular receptors or by extremely fine movements of the head in the gravitational field, such as may have been allowed by the biteboard/headrest restraint system used in this study, which served as an everchanging accelerative stimulus.

Medical experimentation in the elderly.

PubMed

Bernstein, J E; Nelson, F K

1975-07-01

Participation in human experimental research constitutes a major problem for the geriatric subject. Because there is a high incidence of noncontagious disease in the elderly, they are the group most useful for the study of new therapeutic agents or procedures. However, normal aging processes, often coupled with disease of the central nervous system, render elderly persons less able to comprehend the nature and risks of such studies. These factors permit easy exploitation of geriatric subjects in medical experimentation, with possible exposure to a significant risk of serious drug reactions and unnecessary hospitalization. Recent federal regulations have given "special protections" to children, prisoners, and the mentally infirm in experimental research, to guard against abuse of their human rights. A basic requirement is that informed consent be carefully obtained and documented. Such "special protections" should now be extended to geriatric subjects so that there will be no further exploitation in the course of valid clinical research.

Effects of alprazolam and clonidine on carbon dioxide-induced increases in anxiety rating in healthy human subjects

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

Woods, S.W.; Krystal, J.H.; Heninger, G.R.

1989-01-01

In order to investigate possible neurobiologic mechanisms underlying carbon dioxide-induced anxiety, the effects of oral alprazolam 0.75 mg and intravenous clonidine 2 mcg/kg on CO/sub 2/-induced increases in ratings of subjective anxiety, pulse rate, and ventilation were measured in healthy human subjects. Pretreatment with alprazolam but not with clonidine significantly reduced the CO/sub 2/-induced increases in ratings of anxiety. Neither drug altered CO/sub 2/-induced increases in pulse rate or ventilatory responses. Clonidine did produce potent sedative and hypotensive effects. The behavioral data suggest that the mechanisms through which CO/sub 2/ induces anxiety-like effects involve neural systems regulated by benzodiazepine receptorsmore » and, secondly, that they appear not to require normal functioning of noradrenergic systems. Carbon dioxide may provide a useful model system for identification of new drugs with anxiolytic properties.« less

Normative aspects of the human body.

PubMed

Siep, Ludwig

2003-04-01

In cultural history the human body has been the object of a great variety of opposing valuations, ranging from "imago dei" to "the devil's tool". At present, the body is commonly regarded as a mere means to fulfill the wishes of its "owner". According to these wishes it can be technically improved in an unlimited way. Against this view the text argues for a conception of the human body as a valuable "common heritage". The "normal" human body as the result of natural and cultural history is an essential condition of the modern social and legal order. The consequences of its technical alteration should be the subject of public debates and common decisions.

Quantifying Pilot Contribution to Flight Safety during Drive Shaft Failure

NASA Technical Reports Server (NTRS)

Kramer, Lynda J.; Etherington, Tim; Last, Mary Carolyn; Bailey, Randall E.; Kennedy, Kellie D.

2017-01-01

Accident statistics cite the flight crew as a causal factor in over 60% of large transport aircraft fatal accidents. Yet, a well-trained and well-qualified pilot is acknowledged as the critical center point of aircraft systems safety and an integral safety component of the entire commercial aviation system. The latter statement, while generally accepted, cannot be verified because little or no quantitative data exists on how and how many accidents/incidents are averted by crew actions. A joint NASA/FAA high-fidelity motion-base simulation experiment specifically addressed this void by collecting data to quantify the human (pilot) contribution to safety-of-flight and the methods they use in today's National Airspace System. A human-in-the-loop test was conducted using the FAA's Oklahoma City Flight Simulation Branch Level D-certified B-737-800 simulator to evaluate the pilot's contribution to safety-of-flight during routine air carrier flight operations and in response to aircraft system failures. These data are fundamental to and critical for the design and development of future increasingly autonomous systems that can better support the human in the cockpit. Eighteen U.S. airline crews flew various normal and non-normal procedures over a two-day period and their actions were recorded in response to failures. To quantify the human's contribution to safety of flight, crew complement was used as the experiment independent variable in a between-subjects design. Pilot actions and performance during single pilot and reduced crew operations were measured for comparison against the normal two-crew complement during normal and non-normal situations. This paper details the crew's actions, including decision-making, and responses while dealing with a drive shaft failure - one of 6 non-normal events that were simulated in this experiment.

The Plasma Disappearance Time and Catabolic Half-Life of I 131-Labelled Normal Human Gamma Globulin in Amyloidosis and in Rheumatoid Arthritis

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

Mills, John A.; Calkins, Evan; Cohen, Alan S.

1961-10-01

The serum survival time and catabclic half-life of intravenously injected I 131-labeled pooled human gamma globulin - were studied in three patients with amyloidosis, four patients with rheumatoid arthritis, and three normal controls. The half-time of gamma globulin survival in the controsubjects ranged from 16.5 to 30 days. Two patients with amyloidosis, one primary and one secondary, both with the nephrotic syndrome, exhibited shortened serum half-times of 4.5 and 11 days, respectively. The serum half-time of the latter patient, before the appearance of clinical amyloidosis, was 14 days. One patient with primary amyloidosis but without nephrosis exhibited a half-time ofmore » serum gamma globulin disappearance of 21 days. The half-time of gamma globulin disappearance in four patients with chronic active rheumatoid arthritis varied between 19.5 and 8.5 days. The lower figure was found in a patient having a high titer of rheumatoid factor. If this subject is excepted, the average half- time in three rheumatoid subjects is 17 days. The catabolic half-life of the iodinated gamma globulin agreed in most instances with the serum half-time. The calculated distribution space of the injected gamma globulin showed no consistent alteration in either amyloidosis or rheumatoid arthritis as compared with the control subjects. Since the nephrotic syndrome from other causes may produce an accelerated catabolic half-life, a similar finding on these subjects cannot be ascribed to amyloidosis.« less

Experience with a commercial preparation of 125I-labelled human albumin for study of albumin metabolism

PubMed Central

Ballantyne, Fiona C.; Fleck, A.

1973-01-01

Evaluation of a commercial preparation of 125I-labelled albumin for use in the study of albumin metabolism is described. In eight subjects with normal albumin metabolism the proportion of the dose of radioiodide excreted was stable throughout a period of 17 days, indicating that there was no excessive denaturation of the iodinated albumin. Characteristics of albumin metabolism—pool sizes, catabolic rate, etc—were in agreement with currently accepted normal values. It is concluded that this preparation of iodinated albumin is suitable for metabolic use. PMID:4727059

Elevated serum level of human alkaline phosphatase in obesity.

PubMed

Khan, Abdul Rehman; Awan, Fazli Rabbi; Najam, Syeda Sadia; Islam, Mehboob; Siddique, Tehmina; Zain, Maryam

2015-11-01

To investigate a correlation between serum alkaline phosphatase level and body mass index in human subjects. The comparative cross-sectional study was carried out at the National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan, from April 2012 to June 2013. Blood serum alkaline phosphatase levels were estimated and the subjects were divided into three sub-groups on the basis of their body mass. normal weight (<25kg/m2), overweight (25-27kg/m2) and obese (>27kg/m2) subjects. The serum samples were used for the estimation of clinically important biochemical parameters, using commercial kits on clinical chemistry analyser. Of the 197 subjects, 97(49%) were obese and 100(51%) were non-obese. The serum alkaline phosphatase level increased in obese (214±6.4 IU/L) compared to the non-obese subjects (184.5±5 IU/L). Furthermore, a significant linear relationship (r=0.3;p-0.0001) was found between serum alkaline phosphatase and body mass index. Other biochemical variables were not correlated to the body mass index. Over activity and higher amounts of alkaline phosphatase were linked to the development of obesity.

Dynamic Knee Alignment and Collateral Knee Laxity and Its Variations in Normal Humans

PubMed Central

Deep, Kamal; Picard, Frederic; Clarke, Jon V.

2015-01-01

Alignment of normal, arthritic, and replaced human knees is a much debated subject as is the collateral ligamentous laxity. Traditional quantitative values have been challenged. Methods used to measure these are also not without flaws. Authors review the recent literature and a novel method of measurement of these values has been included. This method includes use of computer navigation technique in clinic setting for assessment of the normal or affected knee before the surgery. Computer navigation has been known for achievement of alignment accuracy during knee surgery. Now its use in clinic setting has added to the inventory of measurement methods. Authors dispel the common myth of straight mechanical axis in normal knees and also look at quantification of amount of collateral knee laxity. Based on the scientific studies, it has been shown that the mean alignment is in varus in normal knees. It changes from lying non-weight-bearing position to standing weight-bearing position in both coronal and the sagittal planes. It also varies with gender and race. The collateral laxity is also different for males and females. Further studies are needed to define the ideal alignment and collateral laxity which the surgeon should aim for individual knees. PMID:26636090

Effect of external viscous load on head movement

NASA Technical Reports Server (NTRS)

Nam, M.-H.; Lakshminarayanan, V.; Stark, L. W.

1984-01-01

Quantitative measurements of horizontal head rotation were obtained from normal human subjects intending to make 'time optimal' trajectories between targets. By mounting large, lightweight vanes on the head, viscous damping B, up to 15 times normal could be added to the usual mechanical load of the head. With the added viscosity, the head trajectory was slowed and of larger duration (as expected) since fixed and maximal (for that amplitude) muscle forces had to accelerate the added viscous load. This decreased acceleration and velocity and longer duration movement still ensued in spite of adaptive compensation; this provided evidence that quasi-'time optimal' movements do indeed employ maximal muscle forces. The adaptation to this added load was rapid. Then the 'adapted state' subjects produced changed trajectories. The adaptation depended in part on the differing detailed instructions given to the subjects. This differential adaptation provided evidence for the existence of preprogrammed controller signals, sensitive to intended criterion, and neurologically ballistic or open loop rather than modified by feedback from proprioceptors or vision.

Experimental human exposure to inhaled grain dust and ammonia: towards a model of concentrated animal feeding operations.

PubMed

Sigurdarson, Sigurdur T; O'Shaughnessy, Patrick T; Watt, Janet A; Kline, Joel N

2004-10-01

Ammonia and endotoxin-rich dust are present in high concentrations in swine confinement facilities; exposure to this environment is linked to workers' respiratory problems. We hypothesized that experimental exposure to ammonia and dust would impair pulmonary function, and that these exposures would be synergistic. We exposed six normal subjects and eight subjects with mild asthma to ammonia (16-25 ppm) and/or endotoxin-rich grain dust (4 mg/m3). Pulmonary function and exhaled NOx were measured before and after exposure. There was no significant change in pulmonary function in the normal subjects following any of the exposure conditions. Among asthmatics, a significant transient decrease in FEV1 was induced by grain dust, but was not altered by ammonia; increased bronchial hyperreactivity was also noted in this group. In a vulnerable population, exposure to grain dust results in transient airflow obstruction. Short-term exposure to ammonia does not increase this response.

Part A: Assessing the performance of the COMFA outdoor thermal comfort model on subjects performing physical activity

NASA Astrophysics Data System (ADS)

Kenny, Natasha A.; Warland, Jon S.; Brown, Robert D.; Gillespie, Terry G.

2009-09-01

This study assessed the performance of the COMFA outdoor thermal comfort model on subjects performing moderate to vigorous physical activity. Field tests were conducted on 27 subjects performing 30 min of steady-state activity (walking, running, and cycling) in an outdoor environment. The predicted COMFA budgets were compared to the actual thermal sensation (ATS) votes provided by participants during each 5-min interval. The results revealed a normal distribution in the subjects’ ATS votes, with 82% of votes received in categories 0 (neutral) to +2 (warm). The ATS votes were significantly dependent upon sex, air temperature, short and long-wave radiation, wind speed, and metabolic activity rate. There was a significant positive correlation between the ATS and predicted budgets (Spearman’s rho = 0.574, P < 0.01). However, the predicted budgets did not display a normal distribution, and the model produced erroneous estimates of the heat and moisture exchange between the human body and the ambient environment in 6% of the cases.

Zn concentration in plasma and gastric fluid in patients with upper gastrointestinal disease

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

Kadakia, S.C.; Wong, R.H.K.; Maydonovitch, C.

1986-03-05

Very few data are available about Zn in gastrointestinal fluids in humans. To obtain data in one such fluid Zn was measured in plasma and gastric fluid, obtained by direct visual aspiration through an endoscope placed into the gastric fundus, in 36 subjects with normal gastrointestinal mucosa (N) and in 36 patients with the following upper gastrointestinal pathology confirmed by endoscopy: 13 with esophagitis (E), 9 with gastritis (G) and 14 with duodenal ulcer disease (DU). Plasma and gastric fluid Zn were estimated by flame atomic absorption spectrophotometry. Mean plasma Zn was significantly lower than normal in patients with Emore » (N, 87 +/- 2 ..mu..g/dl, M +/- SEM; E, 75 +/- 4, p < 0.01) but plasma values were similar to normal in the other patient groups (G, 89 +/- 4; DU, 87 +/- 2). Mean gastric fluid zinc in G was significantly higher than in normal subjects (G, 664 +/- 159 ..mu..g/L; N, 360 +/- 43, p < 0.02) but not significantly different from normal in patients with DU or E (DU, 402 +/- 76; E, 307 +/- 55). Mean gastric fluid Zn in women with DU was approximately 45% higher than in men with DU, although it was 17% lower in normal women than in normal men. Compared to other normal tissues gastric fluid Zn is about 1/3 that in serum and about 3 times that in saliva. These results indicate that Zn in plasma and gastric fluid is altered in some upper gastrointestinal diseases.« less

Studies on human urinary arylamidases

NASA Technical Reports Server (NTRS)

Raina, P. N.; Ellis, S.

1975-01-01

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

Human disturbances of waterfowl: An annotated bibliography

USGS Publications Warehouse

Dahlgren, R.B.; Korschgen, C.E.

1992-01-01

The expansion of outdoor recreation greatly increased the interaction between the public, waterfowl, and waterfowl habitat. The effects of these interactions on waterfowl habitats are visible and obvious, whereas the effects of interactions that disrupt the normal behavior of waterfowl are subtle and often overlooked, but perhaps no less harmful than destruction of habitat. Resource managers and administrators require information on the types, magnitude, and effect of disturbances from human contact with wildlife. This bibliography contains annotations for 211 articles with information about effects of human disturbances on waterfowl. Indexes are provided by subject or key words, geographic locations, species of waterfowl, and authors.

Lactose digestion by human jejunal biopsies: the relationship between hydrolysis and absorption.

PubMed Central

Dawson, D J; Lobley, R W; Burrows, P C; Miller, V; Holmes, R

1986-01-01

The relationship between lactose hydrolysis and absorption of released glucose was investigated by determining the kinetics of lactose digestion by jejunal biopsies incubated in vitro. Lactase activity in intact biopsies correlated with conventional assay of tissue homogenates (r = 0.85, p less than 0.001), and glucose uptake from 28 mM lactose was directly proportional to lactase activity (r = 0.95, p less than 0.001) in 21 subjects with normal lactase levels, six with hypolactasia (primary or secondary to coeliac disease) and two with lactose intolerance but normal lactase activity. Kinetic analysis at 0.56-56 mM lactose in five normal subjects showed saturable kinetics for hydrolysis (app Km = 33.9 +/- 2.2 mM; app Vmax = 26.5 +/- 1.1 nmol/min/mg dry weight) but glucose uptake could be fitted to a model either of saturable uptake (app Kt = 47.2 +/- 0.3 mM; app Jmax = 14.1 +/- 0.2 nmol/min/mg) or saturable uptake plus a linear component (app Kt = 21.3 +/- 1.15; app Jmax = 4.59 +/- 0.12; app Kd = 0.093 +/- 0.010 nmol/min/mg/mM). The proportion of glucose taken into the tissue did not significantly exceed 50% of the total released at any lactose concentration suggesting the lack of an efficient capture mechanism for the released glucose. The results suggest that lactose hydrolysis is the rate limiting step in the overall absorption of glucose from lactose in vitro, and that the relationship between hydrolysis and absorption is the same in normal subjects and in hypolactasic subjects. PMID:3084346

The relationship of normal body temperature, end-expired breath temperature, and BAC/BrAC ratio in 98 physically fit human test subjects.

PubMed

Cowan, J Mack; Burris, James M; Hughes, James R; Cunningham, Margaret P

2010-06-01

The relationship between normal body temperature, end-expired breath temperature, and blood alcohol concentration (BAC)/breath alcohol concentration (BrAC) ratio was studied in 98 subjects (84 men, 14 women). Subjects consumed alcohol sufficient to produce a BrAC of at least 0.06 g/210 L 45-75 min after drinking. Breath samples were analyzed using an Intoxilyzer 8000 specially equipped to measure breath temperature. Venous blood samples and body temperatures were then taken. The mean body temperature of the men (36.6 degrees C) was lower than the women (37.0 degrees C); however, their mean breath temperatures were virtually identical (men: 34.5 degrees C; women: 34.6 degrees C). The BAC exceeded the BrAC for every subject. BAC/BrAC ratios were calculated from the BAC and BrAC analytical results. There was no difference in the BAC/BrAC ratios for men (1:2379) and women (1:2385). The correlation between BAC and BrAC was high (r = 0.938, p < 0.0001), whereas the correlations between body temperature and end-expired breath temperature, body temperature and BAC/BrAC ratio, and breath temperature and BAC/BrAC ratio were much lower. Neither normal body temperature nor end-expired breath temperature was strongly associated with BAC/BrAC ratio.

Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma

PubMed Central

Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick

2002-01-01

Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

A SCN10A SNP biases human pain sensitivity

PubMed Central

Duan, Guangyou; Han, Chongyang; Wang, Qingli; Guo, Shanna; Zhang, Yuhao; Ying, Ying; Huang, Penghao; Zhang, Li; Macala, Lawrence; Shah, Palak; Zhang, Mi; Li, Ningbo; Dib-Hajj, Sulayman D; Zhang, Xianwei

2016-01-01

Background: Nav1.8 sodium channels, encoded by SCN10A, are preferentially expressed in nociceptive neurons and play an important role in human pain. Although rare gain-of-function variants in SCN10A have been identified in individuals with painful peripheral neuropathies, whether more common variants in SCN10A can have an effect at the channel level and at the dorsal root ganglion, neuronal level leading to a pain disorder or an altered normal pain threshold has not been determined. Results: Candidate single nucleotide polymorphism association approach together with experimental pain testing in human subjects was used to explore possible common SCN10A missense variants that might affect human pain sensitivity. We demonstrated an association between rs6795970 (G > A; p.Ala1073Val) and higher thresholds for mechanical pain in a discovery cohort (496 subjects) and confirmed it in a larger replication cohort (1005 female subjects). Functional assessments showed that although the minor allele shifts channel activation by −4.3 mV, a proexcitatory attribute, it accelerates inactivation, an antiexcitatory attribute, with the net effect being reduced repetitive firing of dorsal root ganglion neurons, consistent with lower mechanical pain sensitivity. Conclusions: At the association and mechanistic levels, the SCN10A single nucleotide polymorphism rs6795970 biases human pain sensitivity. PMID:27590072

Minimizing center of mass vertical movement increases metabolic cost in walking.

PubMed

Ortega, Justus D; Farley, Claire T

2005-12-01

A human walker vaults up and over each stance limb like an inverted pendulum. This similarity suggests that the vertical motion of a walker's center of mass reduces metabolic cost by providing a mechanism for pendulum-like mechanical energy exchange. Alternatively, some researchers have hypothesized that minimizing vertical movements of the center of mass during walking minimizes the metabolic cost, and this view remains prevalent in clinical gait analysis. We examined the relationship between vertical movement and metabolic cost by having human subjects walk normally and with minimal center of mass vertical movement ("flat-trajectory walking"). In flat-trajectory walking, subjects reduced center of mass vertical displacement by an average of 69% (P = 0.0001) but consumed approximately twice as much metabolic energy over a range of speeds (0.7-1.8 m/s) (P = 0.0001). In flat-trajectory walking, passive pendulum-like mechanical energy exchange provided only a small portion of the energy required to accelerate the center of mass because gravitational potential energy fluctuated minimally. Thus, despite the smaller vertical movements in flat-trajectory walking, the net external mechanical work needed to move the center of mass was similar in both types of walking (P = 0.73). Subjects walked with more flexed stance limbs in flat-trajectory walking (P < 0.001), and the resultant increase in stance limb force generation likely helped cause the doubling in metabolic cost compared with normal walking. Regardless of the cause, these findings clearly demonstrate that human walkers consume substantially more metabolic energy when they minimize vertical motion.

Prodromal disease: Immune responses of the host macrophage system to humoral factors

NASA Technical Reports Server (NTRS)

Criswell, B. S.; Knight, V.

1973-01-01

A composite is presented of nine studies, each yielding information contributing toward an understanding of methods designed to detect disease during the prodromal stages. The data further point to new areas of study that might be useful in early diagnoses. Five of the none experiments were done in mice. Four of these involved acute infectious disease states and one involved a chronic autoimmune type disease. Of the numerous perimeters studied of the acute diseases, the uptake of H3- thymidine by peripheral blood lymphocytes appeared to yield the earliest indication of disease. This test was not useful in studying the chronic disease state. Four of the nine studies involved application of diagnostic technics to human disease. A normal baseline for H3-thymidine incorporation by human lymphocytes was determined. A subject with severe combined immunodeficiency disease was studied. A human volunteer study was done using Influenza A live attenuated vaccine. Finally, a human volunteer study of subjects infected with Influenza A was done.

Method for quantifying optical properties of the human lens

DOEpatents

Loree, T.R.; Bigio, I.J.; Zuclich, J.A.; Shimada, Tsutomu; Strobl, K.

1999-04-13

A method is disclosed for quantifying optical properties of the human lens. The present invention includes the application of fiberoptic, OMA-based instrumentation as an in vivo diagnostic tool for the human ocular lens. Rapid, noninvasive and comprehensive assessment of the optical characteristics of a lens using very modest levels of exciting light are described. Typically, the backscatter and fluorescence spectra (from about 300- to 900-nm) elicited by each of several exciting wavelengths (from about 300- to 600-nm) are collected within a few seconds. The resulting optical signature of individual lenses is then used to assess the overall optical quality of the lens by comparing the results with a database of similar measurements obtained from a reference set of normal human lenses having various ages. Several metrics have been identified which gauge the optical quality of a given lens relative to the norm for the subject`s chronological age. These metrics may also serve to document accelerated optical aging and/or as early indicators of cataract or other disease processes. 8 figs.

Viscoelastic properties of the posterior eye of normal subjects, patients with age-related macular degeneration, and pigs.

PubMed

Zhang, Zhen Huan; Pan, Meng Xin; Cai, Jia Tong; Weiland, James D; Chen, Kinon

2018-03-26

The purpose of this study is to measure, characterize, and compare the viscoelastic properties of the posterior eye of advanced dry age-related macular degeneration (AMD) patients, age-matched normal subjects, and pigs (3 groups). Ten horizontal and ten vertical strips of the macula retina and the underneath choroid and sclera were obtained for each group, respectively. They were examined by incremental stress-relaxation cycles in body-temperature saline. Mechanical response was characterized by the quasi-linear viscoelastic model. All the tissues were shown to be nonlinear viscoelastic. Stiffening and isotropization, increased relaxation, and softening and isotropization were found in AMD retina, choroid, and sclera, respectively, which are the mechanical features of the atherosclerotic process. The patients' medical records were in accordance with epidemiological studies indicating a relationship between the advanced AMD and atherosclerotic vascular disease (ASVD). Moreover, many differences were found between the viscoelastic properties of porcine and normal human retina, choroid, and sclera. The results suggest that AMD is associated with ASVD through a mechanism involving abnormal retinal, choroidal, and scleral mechanics similar to those seen in the atherosclerotic process. Moreover, researchers should be aware of mechanical differences when using porcine posterior eyes as a substitute for human posterior eyes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

Zn concentration in esophageal tissue in patients with and without upper gastrointestinal disease

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

Wong, R.K.H.; Kadakia, S.C.; Maydonovitch, C.

1986-03-05

Measurements of tissue Zn in humans with upper gastrointestinal disease could provide information about underlying pathophysiology but these data have never been obtained. With recent endoscopic methods they obtained 2-6 mg pinch mucosal biopsies of epithelium and lamina propria from proximal (P), middle (M) and distal (D) areas of esophagus under direct vision through a flexible 1 cm endoscope in 35 subjects without gastrointestinal disease (N) and in 35 patients with the following endoscopically proven gastrointestinal pathology: 12 with esophagitis (E), 14 with duodenal ulcer disease (DU) and 9 with gastritis (G). Samples were dried, weighed, digested with HNO/sub 3/,more » dried, resuspended in 3% HNO/sub 3/ and Zn estimated by flame atomic absorption spectrophotometry. Esophageal Zn in N decreased progressively as biopsies extended from P to D (P, 108 +/- 29 ..mu..g/g dry weight, Mean +/- SEM; M, 158 +/- 23; D, 134 +/- 16) but this pattern was generally reversed in patients, with D consistently demonstrating Zn elevated 50-120% above normal. The greatest increase was in G in whom Zn in D was more than twice normal (DU, 290 +/- 76, p < 0.01). These are the first Zn levels obtained from esophagus in living human subjects and indicate (1) a specific pattern of Zn distribution in normal esophagus and (2) a significantly altered pattern in D in several diseases of the upper gastrointestinal tract.« less

75 FR 35279 - Revocation of Regulations Banning Certain Baby-Walkers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-21

... injuring portions of the human body when in normal use or when subjected to reasonably foreseeable damage... allow an infant's finger, toe, or other body part to be inserted, in whole or in part, and injured by... of Michigan, May 31, 1975.) This data set sampled body measurements of children from 2 weeks to 13...

Metabolic effects of dark chocolate consumption on energy, gut microbiota, and stress-related metabolism in free-living subjects.

PubMed

Martin, Francois-Pierre J; Rezzi, Serge; Peré-Trepat, Emma; Kamlage, Beate; Collino, Sebastiano; Leibold, Edgar; Kastler, Jürgen; Rein, Dietrich; Fay, Laurent B; Kochhar, Sunil

2009-12-01

Dietary preferences influence basal human metabolism and gut microbiome activity that in turn may have long-term health consequences. The present study reports the metabolic responses of free living subjects to a daily consumption of 40 g of dark chocolate for up to 14 days. A clinical trial was performed on a population of 30 human subjects, who were classified in low and high anxiety traits using validated psychological questionnaires. Biological fluids (urine and blood plasma) were collected during 3 test days at the beginning, midtime and at the end of a 2 week study. NMR and MS-based metabonomics were employed to study global changes in metabolism due to the chocolate consumption. Human subjects with higher anxiety trait showed a distinct metabolic profile indicative of a different energy homeostasis (lactate, citrate, succinate, trans-aconitate, urea, proline), hormonal metabolism (adrenaline, DOPA, 3-methoxy-tyrosine) and gut microbial activity (methylamines, p-cresol sulfate, hippurate). Dark chocolate reduced the urinary excretion of the stress hormone cortisol and catecholamines and partially normalized stress-related differences in energy metabolism (glycine, citrate, trans-aconitate, proline, beta-alanine) and gut microbial activities (hippurate and p-cresol sulfate). The study provides strong evidence that a daily consumption of 40 g of dark chocolate during a period of 2 weeks is sufficient to modify the metabolism of free living and healthy human subjects, as per variation of both host and gut microbial metabolism.

Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans.

PubMed

Saunders, J P; Donner, T W; Sadler, J H; Levin, G V; Makris, N G

1999-04-01

D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics. In addition, effects of subchronic D-tagatose ingestion on fasting plasma phosphorus, magnesium, lipids, and glucose homeostasis were studied. Eight normal subjects and eight subjects with Type 2 diabetes participated in this two-phase study. Each group was comprised of four males and four females. In the first phase, all subjects were given separate 75 g 3-h oral glucose and D-tagatose tolerance tests. Uric acid, phosphorus, and magnesium were determined in blood samples collected from each subject at 0, 30, 60, 120, and 180 min after dose. In the 8-week phase of the study, the normals were randomly placed into two groups which received 75 g of either D-tagatose or sucrose (25 g with each meal) daily for 8 weeks. The diabetics were randomized into two groups which received either 75 g D-tagatose or no supplements of sugar daily for 8 weeks. Uric acid, phosphorus, magnesium, lipids, glycosylated hemoglobin, glucose, and insulin were determined in fasting blood plasma of all subjects at baseline (time zero) and biweekly over the 8 weeks. The 8-week test did not demonstrate an increase in fasting plasma uric acid in response to the daily intake of D-tagatose. However, a transient increase of plasma uric acid levels was observed after single doses of 75 g of D-tagatose in the tolerance test. Plasma uric acid levels were found to rise and peak at 60 min after such dosing. No clinical relevance was attributed to this treatment-related effect because excursions of plasma uric acid levels above the normal range were small and were of short duration. Consistent with earlier observations on fructose, the increase of plasma uric acid was associated with a slight decrease of plasma phosphorus and a slight increase of magnesium. The daily ingestion of D-tagatose for 8 weeks had no effect on fasting plasma magnesium, phosphorus, cholesterol, triglycerides, glycosylated hemoglobin, glucose, and insulin levels. The ingestion of three 25-g doses per day for a period of 8 weeks resulted in varying amounts of flatulence in seven of the eight subjects, and some degree of diarrhea in six subjects. D-tagatose holds promise as a sweetener with no adverse clinical effects observed in these studies. Copyright 1999 Academic Press.

Pronounced reduction of acquisition of conditioned eyeblink responses in young adults with focal cerebellar lesions impedes conclusions on the role of the cerebellum in extinction and savings.

PubMed

Ernst, T M; Beyer, L; Mueller, O M; Göricke, S; Ladd, M E; Gerwig, M; Timmann, D

2016-05-01

Human cerebellar lesion studies provide good evidence that the cerebellum contributes to the acquisition of classically conditioned eyeblink responses (CRs). As yet, only one study used more advanced methods of lesion-symptom (or lesion-behavior) mapping to investigate which cerebellar areas are involved in CR acquisition in humans. Likewise, comparatively few studies investigated the contribution of the human cerebellum to CR extinction and savings. In this present study, young adults with focal cerebellar disease were tested. A subset of participants was expected to acquire enough conditioned responses to allow the investigation of extinction and saving effects. 19 participants with chronic surgical lesions of the cerebellum and 19 matched control subjects were tested. In all cerebellar subjects benign tumors of the cerebellum had been surgically removed. Eyeblink conditioning was performed using a standard short delay protocol. An initial unpaired control phase was followed by an acquisition phase, an extinction phase and a subsequent reacquisition phase. Structural 3T magnetic resonance images of the brain were acquired on the day of testing. Cerebellar lesions were normalized using methods optimized for the cerebellum. Subtraction analysis and Liebermeister tests were used to perform lesion-symptom mapping. As expected, CR acquisition was significantly reduced in cerebellar subjects compared to controls. Reduced CR acquisition was significantly more likely in participants with lesions of lobule VI and Crus I extending into Crus II (p<0.05, Liebermeister test). Cerebellar subjects could be subdivided into two groups: a smaller group (n=5) which showed acquisition, extinction and savings within the normal range; and a larger group (n=14) which did not show acquisition. In the latter, no conclusions on extinction or savings could be drawn. Previous findings were confirmed that circumscribed areas in lobule VI and Crus I are of major importance in CR acquisition. In addition, the present data suggest that if the critical regions of the cerebellar cortex are lesioned, the ability to acquire CRs is not only reduced but abolished. Subjects with lesions outside these critical areas, on the other hand show preserved acquisition, extinction and saving effects. As a consequence, studies in human subjects with cerebellar lesions do not allow drawing conclusions on CR extinction and savings. In light of the present findings, previous reports of reduced extinction in humans with circumscribed cerebellar disease need to be critically reevaluated. Copyright © 2016 Elsevier Ltd. All rights reserved.

High altitude cognitive performance and COPD interaction

PubMed Central

Kourtidou-Papadeli, C; Papadelis, C; Koutsonikolas, D; Boutzioukas, S; Styliadis, C; Guiba-Tziampiri, O

2008-01-01

Introduction: Thousands of people work and perform everyday in high altitude environment, either as pilots, or shift workers, or mountaineers. The problem is that most of the accidents in this environment have been attributed to human error. The objective of this study was to assess complex cognitive performance as it interacts with respiratory insufficiency at altitudes of 8000 feet and identify the potential effect of hypoxia on safe performance. Methods: Twenty subjects participated in the study, divided in two groups: Group I with mild asymptomatic chronic obstructive pulmonary disease (COPD), and Group II with normal respiratory function. Altitude was simulated at 8000 ft. using gas mixtures. Results: Individuals with mild COPD experienced notable hypoxemia with significant performance decrements and increased number of errors at cabin altitude, compared to normal subjects, whereas their blood pressure significantly increased. PMID:19048098

Sleep-wake cycle effects on sleep stages, and plasma cortisol and growth secretions

NASA Technical Reports Server (NTRS)

1971-01-01

Studies were made of the effects of various stimuli on sleep stages and of secretion of a number of different hormones during sleep in human subjects. Among the stimuli were vestibular stimulation, the action of L-Dopa, and a three-hour sleep-wake cycle. Hormones observed included plasma cortisol, growth hormone, dehydroisoandrosterone, and luteinizing hormone. Relationships between sleep onset, the presence of Cushing's syndrome or sleep disorders, and ultradian rhythmicity, and hormone secretion were investigated. Sleep patterns and hormone secretion in normal subjects were also studied.

Correction of mutant Fanconi anemia gene by homologous recombination in human hematopoietic cells using adeno-associated virus vector.

PubMed

Paiboonsukwong, Kittiphong; Ohbayashi, Fumi; Shiiba, Haruka; Aizawa, Emi; Yamashita, Takayuki; Mitani, Kohnosuke

2009-11-01

Adeno-associated virus (AAV) vectors have been shown to correct a variety of mutations in human cells by homologous recombination (HR) at high rates, which can overcome insertional mutagenesis and transgene silencing, two of the major hurdles in conventional gene addition therapy of inherited diseases. We examined an ability of AAV vectors to repair a mutation in human hematopoietic cells by HR. We infected a human B-lymphoblastoid cell line (BCL) derived from a normal subject with an AAV, which disrupts the hypoxanthine phosphoribosyl transferase1 (HPRT1) locus, to measure the frequency of AAV-mediated HR in BCL cells. We subsequently constructed an AAV vector encoding the normal sequences from the Fanconi anemia group A (FANCA) locus to correct a mutation in the gene in BCL derived from a FANCA patient. Under optimal conditions, approximately 50% of BCL cells were transduced with an AAV serotype 2 (AAV-2) vector. In FANCA BCL cells, up to 0.016% of infected cells were gene-corrected by HR. AAV-mediated restoration of normal genotypic and phenotypic characteristics in FANCA-mutant cells was confirmed at the DNA, protein and functional levels. The results obtained in the present study indicate that AAV vectors may be applicable for gene correction therapy of inherited hematopoietic disorders.

Increased medial olivocochlear reflex strength in normal-hearing, noise-exposed humans

PubMed Central

2017-01-01

Research suggests that college-aged adults are vulnerable to tinnitus and hearing loss due to exposure to traumatic levels of noise on a regular basis. Recent human studies have associated exposure to high noise exposure background (NEB, i.e., routine noise exposure) with the reduced cochlear output and impaired speech processing ability in subjects with clinically normal hearing sensitivity. While the relationship between NEB and the functions of the auditory afferent neurons are studied in the literature, little is known about the effects of NEB on functioning of the auditory efferent system. The objective of the present study was to investigate the relationship between medial olivocochlear reflex (MOCR) strength and NEB in subjects with clinically normal hearing sensitivity. It was hypothesized that subjects with high NEB would exhibit reduced afferent input to the MOCR circuit which would subsequently lead to reduced strength of the MOCR. In normal-hearing listeners, the study examined (1) the association between NEB and baseline click-evoked otoacoustic emissions (CEOAEs) and (2) the association between NEB and MOCR strength. The MOCR was measured using CEOAEs evoked by 60 dB pSPL linear clicks in a contralateral acoustic stimulation (CAS)-off and CAS-on (a broadband noise at 60 dB SPL) condition. Participants with at least 6 dB signal-to-noise ratio (SNR) in the CAS-off and CAS-on conditions were included for analysis. A normalized CEOAE inhibition index was calculated to express MOCR strength in a percentage value. NEB was estimated using a validated questionnaire. The results showed that NEB was not associated with the baseline CEOAE amplitude (r = -0.112, p = 0.586). Contrary to the hypothesis, MOCR strength was positively correlated with NEB (r = 0.557, p = 0.003). NEB remained a significant predictor of MOCR strength (β = 2.98, t(19) = 3.474, p = 0.003) after the unstandardized coefficient was adjusted to control for effects of smoking, sound level tolerance (SLT) and tinnitus. These data provide evidence that MOCR strength is associated with NEB. The functional significance of increased MOCR strength is discussed. PMID:28886123

As the world turns: short-term human spatial memory in egocentric and allocentric coordinates.

PubMed

Banta Lavenex, Pamela; Lecci, Sandro; Prêtre, Vincent; Brandner, Catherine; Mazza, Christian; Pasquier, Jérôme; Lavenex, Pierre

2011-05-16

We aimed to determine whether human subjects' reliance on different sources of spatial information encoded in different frames of reference (i.e., egocentric versus allocentric) affects their performance, decision time and memory capacity in a short-term spatial memory task performed in the real world. Subjects were asked to play the Memory game (a.k.a. the Concentration game) without an opponent, in four different conditions that controlled for the subjects' reliance on egocentric and/or allocentric frames of reference for the elaboration of a spatial representation of the image locations enabling maximal efficiency. We report experimental data from young adult men and women, and describe a mathematical model to estimate human short-term spatial memory capacity. We found that short-term spatial memory capacity was greatest when an egocentric spatial frame of reference enabled subjects to encode and remember the image locations. However, when egocentric information was not reliable, short-term spatial memory capacity was greater and decision time shorter when an allocentric representation of the image locations with respect to distant objects in the surrounding environment was available, as compared to when only a spatial representation encoding the relationships between the individual images, independent of the surrounding environment, was available. Our findings thus further demonstrate that changes in viewpoint produced by the movement of images placed in front of a stationary subject is not equivalent to the movement of the subject around stationary images. We discuss possible limitations of classical neuropsychological and virtual reality experiments of spatial memory, which typically restrict the sensory information normally available to human subjects in the real world. Copyright © 2011 Elsevier B.V. All rights reserved.

Ultra-high-sensitive optical micro-angiography provides depth resolved visualization of microcirculations within human skin under psoriatic conditions

NASA Astrophysics Data System (ADS)

Qin, Jia; An, Lin; Wang, Ruikang

2011-03-01

Adequate functioning of the peripheral micro vascular in human skin is necessary to maintain optimal tissue perfusion and preserve normal hemodynamic function. There is a growing body of evidence suggests that vascular abnormalities may directly related to several dermatologic diseases, such as psoriasis, port-wine stain, skin cancer, etc. New in vivo imaging modalities to aid volumetric microvascular blood perfusion imaging are there for highly desirable. To address this need, we demonstrate the capability of ultra-high sensitive optical micro angiography to allow blood flow visualization and quantification of vascular densities of lesional psoriasis area in human subject in vivo. The microcirculation networks of lesion and non-lesion skin were obtained after post processing the data sets captured by the system. With our image resolution (~20 μm), we could compare these two types of microcirculation networks both qualitatively and quantitatively. The B-scan (lateral or x direction) cross section images, en-face (x-y plane) images and the volumetric in vivo perfusion map of lesion and non-lesion skin areas were obtained using UHS-OMAG. Characteristic perfusion map features were identified between lesional and non-lesional skin area. A statistically significant difference between vascular densities of lesion and non-lesion skin area was also found using a histogram based analysis. UHS-OMAG has the potential to differentiate the normal skin microcirculation from abnormal human skin microcirculation non-invasively with high speed and sensitivity. The presented data demonstrates the great potential of UHS-OMAG for detecting and diagnosing skin disease such as psoriasis in human subjects.

Assessment of 1H NMR-based metabolomics analysis for normalization of urinary metals against creatinine.

PubMed

Cassiède, Marc; Nair, Sindhu; Dueck, Meghan; Mino, James; McKay, Ryan; Mercier, Pascal; Quémerais, Bernadette; Lacy, Paige

2017-01-01

Proton nuclear magnetic resonance ( 1 H NMR, or NMR) spectroscopy and inductively coupled plasma-mass spectrometry (ICP-MS) are commonly used for metabolomics and metal analysis in urine samples. However, creatinine quantification by NMR for the purpose of normalization of urinary metals has not been validated. We assessed the validity of using NMR analysis for creatinine quantification in human urine samples in order to allow normalization of urinary metal concentrations. NMR and ICP-MS techniques were used to measure metabolite and metal concentrations in urine samples from 10 healthy subjects. For metabolite analysis, two magnetic field strengths (600 and 700MHz) were utilized. In addition, creatinine concentrations were determined by using the Jaffe method. Creatinine levels were strongly correlated (R 2 =0.99) between NMR and Jaffe methods. The NMR spectra were deconvoluted with a target database containing 151 metabolites that are present in urine. A total of 50 metabolites showed good correlation (R 2 =0.7-1.0) at 600 and 700MHz. Metal concentrations determined after NMR-measured creatinine normalization were comparable to previous reports. NMR analysis provided robust urinary creatinine quantification, and was sufficient for normalization of urinary metal concentrations. We found that NMR-measured creatinine-normalized urinary metal concentrations in our control subjects were similar to general population levels in Canada and the United Kingdom. Copyright © 2016 Elsevier B.V. All rights reserved.

The biomechanical effect of artificial and human bone density on stopping and stripping torque during screw insertion.

PubMed

Tsuji, Matthew; Crookshank, Meghan; Olsen, Michael; Schemitsch, Emil H; Zdero, Rad

2013-06-01

Orthopedic surgeons apply torque to metal screws manually by "subjective feel" to obtain adequate fracture fixation, i.e. stopping torque, and attempt to avoid accidental over-tightening that leads to screw-bone interface failure, i.e. stripping torque. Few studies have quantified stripping torque in human bone, and only one older study from 1980 reported stopping/ stripping torque ratio. The present aim was to measure stopping and stripping torque of cortical and cancellous screws in artificial and human bone over a wide range of densities. Sawbone blocks were obtained having densities from 0.08 to 0.80g/cm(3). Sixteen fresh-frozen human femurs of known standardized bone mineral density (sBMD) were also used. Using a torque screwdriver, 3.5-mm diameter cortical screws and 6.5-mm diameter cancellous screws were inserted for adequate tightening as determined subjectively by an orthopedic surgeon, i.e. stopping torque, and then further tightened until failure of the screw-bone interface, i.e. stripping torque. There were weak (R=0.25) to strong (R=0.99) linear correlations of absolute and normalized torque vs. density or sBMD. Maximum stopping torques normalized by screw thread area engaged by the host material were 15.2N/mm (cortical screws) and 13.4N/mm (cancellous screws) in sawbone blocks and 20.9N/mm (cortical screws) and 6.1N/mm (cancellous screws) in human femurs. Maximum stripping torques normalized by screw thread area engaged by the host material were 23.4N/mm (cortical screws) and 16.8N/mm (cancellous screws) in sawbone blocks and 29.3N/mm (cortical screws) and 8.3N/mm (cancellous screws) in human femurs. Combined average stopping/ stripping torque ratios were 80.8% (cortical screws) and 76.8% (cancellous screws) in sawbone blocks, as well as 66.6% (cortical screws) and 84.5% (cancellous screws) in human femurs. Surgeons should be aware of stripping torque limits for human femurs and monitor stopping torque during surgery. This is the first study of the effect of sawbone density or human bone sBMD on stopping and stripping torque. Copyright © 2013 Elsevier Ltd. All rights reserved.

In vivo delineation of subdivisions of the human amygdaloid complex in a high-resolution group template

PubMed Central

Tyszka, J. Michael; Pauli, Wolfgang M.

2016-01-01

The nuclei of the human amygdala remain difficult to distinguish in individual subject structural magnetic resonance images. However, interpretation of the amygdala’s role in whole brain networks requires accurate localization of functional activity to a particular nucleus or subgroup of nuclei. To address this, we constructed high spatial resolution, three-dimensional templates, using joint high accuracy diffeomorphic registration of T1- and T2-weighted structural images from 168 typical adults between 22 and 35 years old released by the Human Connectome Project. Several internuclear boundaries are clearly visible in these templates, which would otherwise be impossible to delineate in individual subject data. A probabilistic atlas of major nuclei and nuclear groups was constructed in this template space and mapped back to individual spaces by inversion of the individual diffeomorphisms. Group level analyses revealed a slight (approximately 2%) bias towards larger total amygdala and nuclear volumes in the right hemisphere. No substantial sex or age differences were found in amygdala volumes normalized to total intracranial volume, or subdivision volumes normalized to amygdala volume. The current delineation provides a finer parcellation of the amygdala with more accurate external boundary definition than current histology-based atlases when used in conjunction with high accuracy registration methods, such as diffeomorphic warping. These templates and delineation are intended to be an open and evolving resource for future functional and structural imaging studies of the human amygdala. PMID:27354150

Cross-orientation suppression in human visual cortex

PubMed Central

Heeger, David J.

2011-01-01

Cross-orientation suppression was measured in human primary visual cortex (V1) to test the normalization model. Subjects viewed vertical target gratings (of varying contrasts) with or without a superimposed horizontal mask grating (fixed contrast). We used functional magnetic resonance imaging (fMRI) to measure the activity in each of several hypothetical channels (corresponding to subpopulations of neurons) with different orientation tunings and fit these orientation-selective responses with the normalization model. For the V1 channel maximally tuned to the target orientation, responses increased with target contrast but were suppressed when the horizontal mask was added, evident as a shift in the contrast gain of this channel's responses. For the channel maximally tuned to the mask orientation, a constant baseline response was evoked for all target contrasts when the mask was absent; responses decreased with increasing target contrast when the mask was present. The normalization model provided a good fit to the contrast-response functions with and without the mask. In a control experiment, the target and mask presentations were temporally interleaved, and we found no shift in contrast gain, i.e., no evidence for suppression. We conclude that the normalization model can explain cross-orientation suppression in human visual cortex. The approach adopted here can be applied broadly to infer, simultaneously, the responses of several subpopulations of neurons in the human brain that span particular stimulus or feature spaces, and characterize their interactions. In addition, it allows us to investigate how stimuli are represented by the inferred activity of entire neural populations. PMID:21775720

Determination of steady state and nonsteady-state glycerol kinetics in humans using deuterium-labeled tracer

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

Beylot, M.; Martin, C.; Beaufrere, B.

1987-04-01

Using deuterium-labeled glycerol as tracer and gas-liquid chromatography-mass spectrometry techniques for the determination of isotopic enrichment, we have developed a simple and ethically acceptable method of determining glycerol appearance rate in humans under steady-state and nonsteady-state conditions. In normal subjects, the appearance rate of glycerol in the post-absorptive state was 2.22 +/- 0.20 mumol X kg-1 X min-1, a value in agreement with those reported in studies with radioactively labeled tracers. The ratio nonesterified fatty acid (NEFA) appearance rate/glycerol appearance rate ranged from 1.95 to 3.40. In insulin-dependent diabetic patients with a mild degree of metabolic control, the appearance ratemore » of glycerol was 2.48 +/- 0.29 mumol X kg-1 X min-1. The volume of distribution of glycerol, determined by the bolus injection technique, was (mean) 0.306 l X kg-1 in normal subjects and 0.308 l X kg-1 in insulin-independent diabetic patients. To evaluate the usefulness of the method for determination of glycerol kinetics in nonsteady-state conditions, we infused six normal subjects with natural glycerol and calculated the isotopically determined glycerol appearance rate using a single compartment model (volume of distribution 0.31 l X kg-1). During these tests, the expected glycerol appearance rates were successively 5.03 +/- 0.33, 7.48 +/- 0.39, 9.94 +/- 0.34, 7.48 +/- 0.39, and 5.03 +/- 0.33 mumol +/- kg-1 X min-1, whereas the corresponding isotopically determined appearance rates were 4.62 +/- 0.45, 6.95 +/- 0.56, 10.85 +/- 0.51, 7.35 +/- 0.34, and 5.28 +/- 0.12 mumol X kg-1 X min-1.« less

Comparison of Serum rAAV Serotype-Specific Antibodies in Patients with Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Inclusion Body Myositis, or GNE Myopathy.

PubMed

Zygmunt, Deborah A; Crowe, Kelly E; Flanigan, Kevin M; Martin, Paul T

2017-09-01

Recombinant adeno-associated virus (rAAV) is a commonly used gene therapy vector for the delivery of therapeutic transgenes in a variety of human diseases, but pre-existing serum antibodies to viral capsid proteins can greatly inhibit rAAV transduction of tissues. Serum was assayed from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), inclusion body myositis (IBM), and GNE myopathy (GNE). These were compared to serum from otherwise normal human subjects to determine the extent of pre-existing serum antibodies to rAAVrh74, rAAV1, rAAV2, rAAV6, rAAV8, and rAAV9. In almost all cases, patients with measurable titers to one rAAV serotype showed titers to all other serotypes tested, with average titers to rAAV2 being highest in all instances. Twenty-six percent of all young normal subjects (<18 years old) had measurable rAAV titers to all serotypes tested, and this percentage increased to almost 50% in adult normal subjects (>18 years old). Fifty percent of all IBM and GNE patients also had antibody titers to all rAAV serotypes, while only 18% of DMD and 0% of BMD patients did. In addition, serum-naïve macaques treated systemically with rAAVrh74 could develop cross-reactive antibodies to all other serotypes tested at 24 weeks post treatment. These data demonstrate that most DMD and BMD patients should be amenable to vascular rAAV-mediated treatment without the concern of treatment blockage by pre-existing serum rAAV antibodies, and that serum antibodies to rAAVrh74 are no more common than those for rAAV6, rAAV8, or rAAV9.

Dysregulation of Galectin-3. Implications for Hermansky-Pudlak Syndrome Pulmonary Fibrosis

PubMed Central

Cullinane, Andrew R.; Yeager, Caroline; Dorward, Heidi; Carmona-Rivera, Carmelo; Wu, Hai Ping; Moss, Joel; O’Brien, Kevin J.; Nathan, Steven D.; Meyer, Keith C.; Rosas, Ivan O.; Helip-Wooley, Amanda; Huizing, Marjan; Gahl, William A.

2014-01-01

The etiology of Hermansky-Pudlak syndrome (HPS) pulmonary fibrosis (HPSPF), a progressive interstitial lung disease with high mortality, is unknown. Galectin-3 is a β-galactoside–binding lectin with profibrotic effects. The objective of this study was to investigate the involvement of galectin-3 in HPSPF. Galectin-3 was measured by ELISA, immunohistochemistry, and immunoblotting in human specimens from subjects with HPS and control subjects. Mechanisms of galectin-3 accumulation were studied by quantitative RT-PCR, Northern blot analysis, membrane biotinylation assays, and rescue of HPS1-deficient cells by transfection. Bronchoalveolar lavage galectin-3 concentrations were significantly higher in HPSPF compared with idiopathic pulmonary fibrosis or that from normal volunteers, and correlated with disease severity. Galectin-3 immunostaining was increased in HPSPF compared with idiopathic pulmonary fibrosis or normal lung tissue. Fibroblasts from subjects with HPS subtypes associated with pulmonary fibrosis had increased galectin-3 protein expression compared with cells from nonfibrotic HPS subtypes. Galectin-3 protein accumulation was associated with reduced Galectin-3 mRNA, normal Mucin 1 levels, and up-regulated microRNA-322 in HPSPF cells. Membrane biotinylation assays showed reduced galectin-3 and normal Mucin 1 expression at the plasma membrane in HPSPF cells compared with control cells, which suggests that galectin-3 is mistrafficked in these cells. Reconstitution of HPS1 cDNA into HPS1-deficient cells normalized galectin-3 protein and mRNA levels, as well as corrected galectin-3 trafficking to the membrane. Intracellular galectin-3 levels are regulated by HPS1 protein. Abnormal accumulation of galectin-3 may contribute to the pathogenesis of HPSPF. PMID:24134621

Hard to “tune in”: neural mechanisms of live face-to-face interaction with high-functioning autistic spectrum disorder

PubMed Central

Tanabe, Hiroki C.; Kosaka, Hirotaka; Saito, Daisuke N.; Koike, Takahiko; Hayashi, Masamichi J.; Izuma, Keise; Komeda, Hidetsugu; Ishitobi, Makoto; Omori, Masao; Munesue, Toshio; Okazawa, Hidehiko; Wada, Yuji; Sadato, Norihiro

2012-01-01

Persons with autism spectrum disorders (ASD) are known to have difficulty in eye contact (EC). This may make it difficult for their partners during face to face communication with them. To elucidate the neural substrates of live inter-subject interaction of ASD patients and normal subjects, we conducted hyper-scanning functional MRI with 21 subjects with autistic spectrum disorder (ASD) paired with typically-developed (normal) subjects, and with 19 pairs of normal subjects as a control. Baseline EC was maintained while subjects performed real-time joint-attention task. The task-related effects were modeled out, and inter-individual correlation analysis was performed on the residual time-course data. ASD–Normal pairs were less accurate at detecting gaze direction than Normal–Normal pairs. Performance was impaired both in ASD subjects and in their normal partners. The left occipital pole (OP) activation by gaze processing was reduced in ASD subjects, suggesting that deterioration of eye-cue detection in ASD is related to impairment of early visual processing of gaze. On the other hand, their normal partners showed greater activity in the bilateral occipital cortex and the right prefrontal area, indicating a compensatory workload. Inter-brain coherence in the right IFG that was observed in the Normal-Normal pairs (Saito et al., 2010) during EC diminished in ASD–Normal pairs. Intra-brain functional connectivity between the right IFG and right superior temporal sulcus (STS) in normal subjects paired with ASD subjects was reduced compared with in Normal–Normal pairs. This functional connectivity was positively correlated with performance of the normal partners on the eye-cue detection. Considering the integrative role of the right STS in gaze processing, inter-subject synchronization during EC may be a prerequisite for eye cue detection by the normal partner. PMID:23060772

Contributions of dysglycemia, obesity and insulin resistance to impaired endothelium-dependent vasodilation in humans

PubMed Central

Han, KA; Patel, Y; Lteif, AA; Chisholm, R; Mather, KJ

2011-01-01

Background Individual effects of hyperglycemia and obesity to impair vascular health are recognized. However, the relative contributions of dysglycemia versus other obesity-related traits to vascular dysfunction have not been systematically evaluated. Methods We undertook a cross-sectional evaluation of factors contributing to vascular function in 271 consecutive subjects, categorized as non-obese normal glucose tolerant (n=115), non-obese dysglycemic (n=32), obese normal glucose tolerant (n=57), obese dysglycemic (n=38), or type 2 diabetic (n=29). Vascular function was measured invasively as leg blood flow responses to methacholine chloride, an endothelium-dependent vasodilator. Categorical and continuous analyses were used to assess the contributions of hyperglycemia to vascular dysfunction. Results Even among normoglycemic subjects, obese subjects had impaired vascular function compared to non-obese subjects (p=0.004). Vascular function was also impaired in non-obese dysglycemic subjects (p=0.04 versus non-obese normoglycemic subjects), to a level comparable to normoglycemic obese subjects. Within obese subject groups, gradations of dysglycemia including the presence of diabetes were not associated with further worsening of these vascular responses beyond the effect of obesity alone (p=NS comparing all obese groups, p<0.001 versus lean normoglycemic subjects). In univariate and multivariable modeling analyses we found that effects of glycemia were less powerful than effects of insulin resistance and obesity on vascular dysfunction. Conclusions Dysglycemia contributes to impaired vascular function in non-obese subjects, but obesity and insulin resistance are more important determinants of vascular function in obese and diabetic subjects. PMID:21309061

The laser Doppler flowmeter for measuring microcirculation in human nasal mucosa.

PubMed

Olsson, P; Bende, M; Ohlin, P

1985-01-01

A new technique, based on the laser doppler principle, for measuring nasal mucosal microcirculation in humans, is presented. With this technique the relation between the blood flow and the temperature of the nasal mucosa was evaluated in healthy subjects exposed to peripheral cold stimulus. A decrease in blood flow and in mucosal temperature was found in all subjects when the feet were exposed to cold water for 5 min. The decrease in blood flow occurred almost momentarily and was restored to normal within the 5 min of exposure, while the drop in mucosal temperature was more gradual and persisted for a longer time. The implication of this study is that the laser doppler flowmeter seems to be a useful tool for estimation of changes in nasal mucosal microcirculation.

Effects of muscle contraction on cervical vestibular evoked myogenic potentials in normal subjects.

PubMed

Rosengren, Sally M

2015-11-01

Cervical vestibular evoked myogenic potentials (cVEMPs) are vestibular-dependent muscle reflexes recorded from the sternocleidomastoid (SCM) muscles in humans. cVEMP amplitude is modulated by stimulus intensity and SCM muscle contraction strength, but the effect of muscle contraction is less well-documented. The effects of intensity and contraction were therefore compared in 25 normal subjects over a wide range of contractions. cVEMPs were recorded at different contraction levels while holding stimulus intensity constant and at different intensities while holding SCM contraction constant. The effect of muscle contraction on cVEMP amplitude was linear for most of the range of muscle contractions in the majority of subjects (mean R(2)=0.93), although there were some nonlinearities when the contraction was either very weak or very strong. Very weak contractions were associated with absent responses, incomplete morphology and prolonged p13 latencies. Normalization of amplitudes, by dividing the p13-n23 amplitude by the muscle contraction estimate, reduced the effect of muscle contraction, but tended to underestimate the amplitude with weak contractions. Minimum contraction levels are required for accurate interpretation of cVEMPs. These data highlight the importance of measuring SCM contraction strength when recording cVEMPs. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension.

PubMed

Nyberg, M; Mortensen, S P; Hellsten, Y

2013-03-01

Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design. Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

[Activities of Psychology Dept., California Univ.

NASA Technical Reports Server (NTRS)

Bridgeman, Bruce

1998-01-01

We have completed two studies during the grant period, with manuscripts published or ready for submission for publication: (1) Dual adaptation and adaptive generalization in the human vestibuloocular reflex and (2) Frequency vs. acceleration specificity in human VOR adaptation. In the 1st study two studies examined the possibility that rotational VOR plasticity is subject to dual adaptation and adaptive generalization. Subjects in the experimental condition were exposed to an altered visual-vestibular environment for about four minutes every day for five consecutive days. The working hours between these testing sessions constituted re-exposure to the normal visual environment. Thus, subjects were repeatedly adapting and re-adapting to both environments which is a condition designed to produce dual adaptation. In each training session a measure of baseline VOR gain was obtained (in the dark). A small laser spot (the only visual stimulus) was systematically moved in the same direction as the subject's head, but by half the angle of rotation (target/head gain = 0.5). This resulted in adaptation values relativized to the non-adapted gain of each subject. These values were then analyzed using an analysis of variance with day and session (within a day) as factors. In the 2nd study human VOR adaption has been assumed to be frequency specific, despite the fact that the semicircular canals are simulated by rotational acceleration and not frequency per se.

Acute hyperhydration reduces athlete biological passport OFF-hr score.

PubMed

Bejder, J; Hoffmann, M F; Ashenden, M; Nordsborg, N B; Karstoft, K; Mørkeberg, J

2016-03-01

Anecdotal evidence suggests that athletes hyperhydrate to mask prohibited substances in urine and potentially counteract suspicious fluctuations in blood parameters in the athlete biological passport (ABP). It is examined if acute hyperhydration changes parameters included in the ABP. Twenty subjects received recombinant human erythropoietin (rhEPO) for 3 weeks. After 10 days of rhEPO washout, 10 subjects ingested normal amount of water (∼ 270 mL), whereas the remaining 10 ingested a 1000 mL bolus of water. Blood variables were measured 20, 40, 60, and 80 min after ingestion. Three days later, the subjects were crossed-over with regard to water ingestion and the procedure was repeated. OFF-hr was reduced by ∼ 4%, ∼ 3%, and ∼ 2% at 40, 60, and 80 min, respectively, after drinking 1000 mL of water, compared with normal water ingestion (P < 0.05). Forty percent of the subjects were identified with atypical blood profiles (99% specificity level) before drinking 1000 mL of water, whereas 11% (n = 18), 10% and 11% (n = 18) were identified 40, 60, and 80 min, respectively, after ingestion. This was different (P < 0.05) compared with normal water intake, where 45% of the subjects were identified before ingestion, and 54% (n = 19), 45%, and 47% (n = 19) were identified 40, 60, and 80 min, respectively, after ingestion. In conclusion, acute hyperhydration reduces ABP OFF-hr and reduces ABP sensitivity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A comparative study on the mechanical energy of the normal, ACL, osteoarthritis, and Parkinson subjects.

PubMed

Bahreinizad, Hossein; Salimi Bani, Milad; Hasani, Mojtaba; Karimi, Mohammad Taghi; Sharifmoradi, Keyvan; Karimi, Alireza

2017-08-09

The influence of various musculoskeletal disorders has been evaluated using different kinetic and kinematic parameters. But the efficiency of walking can be evaluated by measuring the effort of the subject, or by other words the energy that is required to walk. The aim of this study was to identify mechanical energy differences between the normal and pathological groups. Four groups of 15 healthy subjects, 13 Parkinson subjects, 4 osteoarthritis subjects, and 4 ACL reconstructed subjects have participated in this study. The motions of foot, shank and thigh were recorded using a three dimensional motion analysis system. The kinetic, potential and total mechanical energy of each segment was calculated using 3D markers positions and anthropometric measurements. Maximum value and sample entropy of energies was compared between the normal and abnormal subjects. Maximum value of potential energy of OA subjects was lower than the normal subjects. Furthermore, sample entropy of mechanical energy for Parkinson subjects was low in comparison to the normal subjects while sample entropy of mechanical energy for the ACL subjects was higher than that of the normal subjects. Findings of this study suggested that the subjects with different abilities show different mechanical energy during walking.

Effects of Aging and Alterations in Dietary Sodium Intake on Total Nitric Oxide Production

PubMed Central

Schmidt, Rebecca J.; Beierwaltes, William H.; Baylis, Chris

2009-01-01

Animal studies suggest that nitric oxide (NO) deficiency is linked to salt-sensitive hypertension and that NO activity decreases during normal aging. This study investigates the impact of increasing age and manipulations in dietary salt intake on biochemical indices of the NO system in healthy humans. We measured NO2 + NO3 (NOX; stable oxidation products of NO) and cyclic guanosine monophosphate (cGMP; major second messenger) in plasma and urine of 30 healthy subjects aged 22 to 77 years. Subjects were maintained on controlled low NOX and low-, normal-, or high-salt diets for 3 days. Salt sensitivity of blood pressure was seen only in the oldest subjects. Plasma renin activity was suppressed by a high salt intake in all age groups, and baseline values declined with advancing age. Neither age nor salt intake correlated with indices of NO activity over the third 24-hour period of controlled salt intake. In a subgroup of subjects aged 33 ± 4 years challenged with ultrahigh sodium intake (400 mEq/24 h), again there was no increase in NO2 + NO3 or cGMP measures. In contrast to animal studies, there is no correlation in humans between either salt intake or age and total NO production and activity, indicated by NO2 + NO3 and cGMP measures. This does not preclude undetected alterations occurring in NO production and/or activity in strategic locations in the kidney and cardiovascular system. Limitations of blood and urine measurements of NO2 + NO3 and cGMP as indices of NO activity are discussed. PMID:11325670

Cooperative Health Occupation Education (Course Outline), Body Structure and Function I: 8009.08.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

GRADES OR AGES: Twelfth grade. SUBJECT MATTER: The human body processes in normal and in certain abnormal conditions. ORGANIZATION AND PHYSICAL APPEARANCE: The document contains a preface, a list of goals, a list of specific block objectives, a bibliography, a course outline for each of the six blocks, and a quinmester posttest. The six blocks are…

MUC19 expression in human ocular surface and lacrimal gland and its alteration in Sjögren syndrome patients.

PubMed

Yu, D F; Chen, Y; Han, J M; Zhang, H; Chen, X P; Zou, W J; Liang, L Y; Xu, C C; Liu, Z G

2008-02-01

This study investigated the expression of MUC19, a newly discovered gel-forming mucin gene, in normal human lacrimal functional unit components and its alteration in Sjögren syndrome patients. Real-time PCR and immunohistochemistry were performed to determine the expression of MUC19 and MUC5AC in human cornea, conjunctiva, and lacrimal gland tissues. Conjunctival impression cytology specimens were collected from normal control subjects and Sjögren syndrome patients for Real-time PCR, PAS staining, and immunohistochemistry assays. In addition, conjunctiva biopsy specimens from both groups were examined for the expression differences of MUC19 and MUC5AC at both mRNA and protein level. The MUC19 mRNA was found to be present in cornea, conjunctiva and lacrimal gland tissues. The immunohistochemical staining of mucins showed that MUC19 was expressed in epithelial cells from corneal, conjunctival, and lacrimal gland tissues. In contrast, MUC5AC mRNA was only present in conjunctiva and lacrimal gland tissues, but not in cornea. Immunostaining demonstrates the co-staining of MUC19 and MUC5AC in conjunctival goblet cells. Consistent with the significant decrease of mucous secretion, both MUC19 and MUC5AC were decreased in conjunctiva of Sjögren syndrome patients compared to normal subjects. Considering the contribution of gel-forming mucins to the homeostasis of the ocular surface, the decreased expression of MUC19 and MUC5AC in Sjögren syndrome patients suggested that these mucins may be involved in the disruption of the ocular surface homeostasis in this disease.

Hexose transporter mRNAs for GLUT4, GLUT5, and GLUT12 predominate in human muscle.

PubMed

Stuart, Charles A; Yin, Deling; Howell, Mary E A; Dykes, Rhesa J; Laffan, John J; Ferrando, Arny A

2006-11-01

In the past few years, 8 additional members of the facilitative hexose transporter family have been identified, giving a total of 14 members of the SLC2A family of membrane-bound hexose transporters. To determine which of the new hexose transporters were expressed in muscle, mRNA concentrations of 11 glucose transporters (GLUTs) were quantified and compared. RNA from muscle from 10 normal volunteers was subjected to RT-PCR. Primers were designed that amplified 78- to 241-base fragments, and cDNA standards were cloned for GLUT1, GLUT2, GLUT3, GLUT4, GLUT5, GLUT6, GLUT8, GLUT9, GLUT10, GLUT11, GLUT12, and GAPDH. Seven of these eleven hexose transporters were detectable in normal human muscle. The rank order was GLUT4, GLUT5, GLUT12, GLUT8, GLUT11, GLUT3, and GLUT1, with corresponding concentrations of 404 +/- 49, 131 +/- 14, 33 +/- 4, 5.5 +/- 0.5, 4.1 +/- 0.4, 1.2 +/- .0.1, and 0.9 +/- 0.2 copies/ng RNA (means +/- SE), respectively, for the 10 subjects. Concentrations of mRNA for GLUT4, GLUT5, and GLUT12 were much higher than those for the remainder of the GLUTs and together accounted for 98% of the total GLUT isoform mRNA. Immunoblots of muscle homogenates verified that the respective proteins for GLUT4, GLUT5, and GLUT12 were present in normal human muscle. Immunofluorescent studies demonstrated that GLUT4 and GLUT12 were predominantly expressed in type I oxidative fibers; however, GLUT5 was expressed predominantly in type II (white) fibers.

Anatomically Realistic Three-Dimensional Meshes of the Pelvic Floor & Anal Canal for Finite Element Analysis

PubMed Central

Noakes, Kimberley F.; Bissett, Ian P.; Pullan, Andrew J.; Cheng, Leo K.

2014-01-01

Three anatomically realistic meshes, suitable for finite element analysis, of the pelvic floor and anal canal regions have been developed to provide a framework with which to examine the mechanics, via finite element analysis of normal function within the pelvic floor. Two cadaver-based meshes were produced using the Visible Human Project (male and female) cryosection data sets, and a third mesh was produced based on MR image data from a live subject. The Visible Man (VM) mesh included 10 different pelvic structures while the Visible Woman and MRI meshes contained 14 and 13 structures respectively. Each image set was digitized and then finite element meshes were created using an iterative fitting procedure with smoothing constraints calculated from ‘L’-curves. These weights produced accurate geometric meshes of each pelvic structure with average Root Mean Square (RMS) fitting errors of less than 1.15 mm. The Visible Human cadaveric data provided high resolution images, however, the cadaveric meshes lacked the normal dynamic form of living tissue and suffered from artifacts related to postmortem changes. The lower resolution MRI mesh was able to accurately portray structure of the living subject and paves the way for dynamic, functional modeling. PMID:18317929

Automated Identification of Abnormal Adult EEGs

PubMed Central

López, S.; Suarez, G.; Jungreis, D.; Obeid, I.; Picone, J.

2016-01-01

The interpretation of electroencephalograms (EEGs) is a process that is still dependent on the subjective analysis of the examiners. Though interrater agreement on critical events such as seizures is high, it is much lower on subtler events (e.g., when there are benign variants). The process used by an expert to interpret an EEG is quite subjective and hard to replicate by machine. The performance of machine learning technology is far from human performance. We have been developing an interpretation system, AutoEEG, with a goal of exceeding human performance on this task. In this work, we are focusing on one of the early decisions made in this process – whether an EEG is normal or abnormal. We explore two baseline classification algorithms: k-Nearest Neighbor (kNN) and Random Forest Ensemble Learning (RF). A subset of the TUH EEG Corpus was used to evaluate performance. Principal Components Analysis (PCA) was used to reduce the dimensionality of the data. kNN achieved a 41.8% detection error rate while RF achieved an error rate of 31.7%. These error rates are significantly lower than those obtained by random guessing based on priors (49.5%). The majority of the errors were related to misclassification of normal EEGs. PMID:27195311

The importance of light, postural and social cues in the regulation of the plasma cortisol rhythm in man

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Winget, C. M.

1979-01-01

A series of experiments was conducted to assess the role of photoperiodic postural and social cues in the regulation of the plasma cortisol rhythm in normal human subjects. Young healthy adult male volunteers, aged 20-25, were used as the test subjects and were selected following extensive physical and psychological examinations. The time at which peak plasma cortisol concentration occurred was calculated from harmonic curves fitted to each set of 24-hr data from each subject. The findings suggest that the plasma cortisol rhythm is not affected appreciably by the absence of postural change, whereas light and social interaction affect this rhythm profoundly.

Cooperative dynamics in auditory brain response

NASA Astrophysics Data System (ADS)

Kwapień, J.; DrożdŻ, S.; Liu, L. C.; Ioannides, A. A.

1998-11-01

Simultaneous estimates of activity in the left and right auditory cortex of five normal human subjects were extracted from multichannel magnetoencephalography recordings. Left, right, and binaural stimulations were used, in separate runs, for each subject. The resulting time series of left and right auditory cortex activity were analyzed using the concept of mutual information. The analysis constitutes an objective method to address the nature of interhemispheric correlations in response to auditory stimulations. The results provide clear evidence of the occurrence of such correlations mediated by a direct information transport, with clear laterality effects: as a rule, the contralateral hemisphere leads by 10-20 ms, as can be seen in the average signal. The strength of the interhemispheric coupling, which cannot be extracted from the average data, is found to be highly variable from subject to subject, but remarkably stable for each subject.

Braille character discrimination in blindfolded human subjects.

PubMed

Kauffman, Thomas; Théoret, Hugo; Pascual-Leone, Alvaro

2002-04-16

Visual deprivation may lead to enhanced performance in other sensory modalities. Whether this is the case in the tactile modality is controversial and may depend upon specific training and experience. We compared the performance of sighted subjects on a Braille character discrimination task to that of normal individuals blindfolded for a period of five days. Some participants in each group (blindfolded and sighted) received intensive Braille training to offset the effects of experience. Blindfolded subjects performed better than sighted subjects in the Braille discrimination task, irrespective of tactile training. For the left index finger, which had not been used in the formal Braille classes, blindfolding had no effect on performance while subjects who underwent tactile training outperformed non-stimulated participants. These results suggest that visual deprivation speeds up Braille learning and may be associated with behaviorally relevant neuroplastic changes.

High-frequency hearing impairment assessed with cochlear microphonics.

PubMed

Zhang, Ming

2012-09-01

Cochlear microphonic (CM) measurements may potentially become a supplementary approach to otoacoustic emission (OAE) measurements for assessing low-frequency cochlear functions in the clinic. The objective of this study was to investigate the measurement of CMs in subjects with high-frequency hearing loss. Currently, CMs can be measured using electrocochleography (ECochG or ECoG) techniques. Both CMs and OAEs are cochlear responses, while auditory brainstem responses (ABRs) are not. However, there are inherent limitations associated with OAE measurements such as acoustic noise, which can conceal low-frequency OAEs measured in the clinic. However, CM measurements may not have these limitations. CMs were measured in human subjects using an ear canal electrode. The CMs were compared between the high-frequency hearing loss group and the normal-hearing control group. Distortion product OAEs (DPOAEs) and audiogram were also measured. The DPOAE and audiogram measurements indicate that the subjects were correctly selected for the two groups. Low-frequency CM waveforms (CMWs) can be measured using ear canal electrodes in high-frequency hearing loss subjects. The difference in amplitudes of CMWs between the high-frequency hearing loss group and the normal-hearing group is insignificant at low frequencies but significant at high frequencies.

The l-α-Lysophosphatidylinositol/GPR55 System and Its Potential Role in Human Obesity

PubMed Central

Moreno-Navarrete, José María; Catalán, Victoria; Whyte, Lauren; Díaz-Arteaga, Adenis; Vázquez-Martínez, Rafael; Rotellar, Fernando; Guzmán, Rocío; Gómez-Ambrosi, Javier; Pulido, Marina R.; Russell, Wendy R.; Imbernón, Mónica; Ross, Ruth A.; Malagón, María M.; Dieguez, Carlos; Fernández-Real, José Manuel; Frühbeck, Gema; Nogueiras, Ruben

2012-01-01

GPR55 is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenic genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans. PMID:22179809

Microarray analysis on gene regulation by estrogen, progesterone and tamoxifen in human endometrial stromal cells.

PubMed

Ren, Chun-E; Zhu, Xueqiong; Li, Jinping; Lyle, Christian; Dowdy, Sean; Podratz, Karl C; Byck, David; Chen, Hai-Bin; Jiang, Shi-Wen

2015-03-13

Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen. We demonstrated that stromal cells express appreciable levels of estrogen and progesterone receptors and undergo different morphological changes upon hormonal stimulation. Microarray analysis indicated that both estrogen and progesterone induced dramatic alterations in a variety of genes associated with cell structure, transcription, cell cycle, and signaling. However, divergent patterns of changes, and in some genes opposite effects, were observed for the two hormones. A large number of genes are identified as novel targets for hormonal regulation. These hormone-responsive genes may be involved in normal uterine function and the development of endometrial malignancies.

Photoacoustic evaluation of human inflammatory arthritis in human joints

NASA Astrophysics Data System (ADS)

Jo, Janggun; Xu, Guan; Marquardt, April; Girish, Gandikota; Wang, Xueding

2017-03-01

Photoacoustic (PA) imaging combined with ultrasonography (US) holds promise to offer a novel and powerful tool for clinical management of inflammatory arthritis, including early detection and treatment monitoring. As a complement to US, PA imaging can assess additional hemodynamic changes in inflammatory synovium, including hyperemia and hypoxia, both important and early physiological biomarkers of synovitis reflecting the increased metabolic demand and the relatively inadequate oxygen delivery of the inflammatory synovial tissue. In this study on arthritis patients and normal volunteers, the targeted metacarpophalangeal (MCP) joints were imaged using our real-time US-PA dual-modality imaging system. The blood volume and the blood oxygenation in the segmented synovium were quantified, and the results from the arthritis patients were compared to those from the normal volunteers. This initial study on human subjects demonstrated that PA imaging, by working at the optical wavelengths that are sensitive to oxygenated and deoxygenated hemoglobin, is capable of identifying and characterizing inflammation in joints based on the detection of hemodynamic changes.

Development and Feasibility Assessment of a Rotational Orthosis for Walking with Arm Swing.

PubMed

Fang, Juan; Xie, Qing; Yang, Guo-Yuan; Xie, Le

2017-01-01

Interlimb neural coupling might underlie human bipedal locomotion, which is reflected in the fact that people swing their arms synchronously with leg movement in normal gait. Therefore, arm swing should be included in gait training to provide coordinated interlimb performance. The present study aimed to develop a Rotational Orthosis for Walking with Arm Swing (ROWAS), and evaluate its feasibility from the perspectives of implementation, acceptability and responsiveness. We developed the mechanical structures of the ROWAS system in SolidWorks, and implemented the concept in a prototype. Normal gait data were used as the reference performance of the shoulder, hip, knee and ankle joints of the prototype. The ROWAS prototype was tested for function assessment and further evaluated using five able-bodied subjects for user feedback. The ROWAS prototype produced coordinated performance in the upper and lower limbs, with joint profiles similar to those occurring in normal gait. The subjects reported a stronger feeling of walking with arm swing than without. The ROWAS system was deemed feasible according to the formal assessment criteria.

Brain Entropy Mapping Using fMRI

PubMed Central

Wang, Ze; Li, Yin; Childress, Anna Rose; Detre, John A.

2014-01-01

Entropy is an important trait for life as well as the human brain. Characterizing brain entropy (BEN) may provide an informative tool to assess brain states and brain functions. Yet little is known about the distribution and regional organization of BEN in normal brain. The purpose of this study was to examine the whole brain entropy patterns using a large cohort of normal subjects. A series of experiments were first performed to validate an approximate entropy measure regarding its sensitivity, specificity, and reliability using synthetic data and fMRI data. Resting state fMRI data from a large cohort of normal subjects (n = 1049) from multi-sites were then used to derive a 3-dimensional BEN map, showing a sharp low-high entropy contrast between the neocortex and the rest of brain. The spatial heterogeneity of resting BEN was further studied using a data-driven clustering method, and the entire brain was found to be organized into 7 hierarchical regional BEN networks that are consistent with known structural and functional brain parcellations. These findings suggest BEN mapping as a physiologically and functionally meaningful measure for studying brain functions. PMID:24657999

Development and Feasibility Assessment of a Rotational Orthosis for Walking with Arm Swing

PubMed Central

Fang, Juan; Xie, Qing; Yang, Guo-Yuan; Xie, Le

2017-01-01

Interlimb neural coupling might underlie human bipedal locomotion, which is reflected in the fact that people swing their arms synchronously with leg movement in normal gait. Therefore, arm swing should be included in gait training to provide coordinated interlimb performance. The present study aimed to develop a Rotational Orthosis for Walking with Arm Swing (ROWAS), and evaluate its feasibility from the perspectives of implementation, acceptability and responsiveness. We developed the mechanical structures of the ROWAS system in SolidWorks, and implemented the concept in a prototype. Normal gait data were used as the reference performance of the shoulder, hip, knee and ankle joints of the prototype. The ROWAS prototype was tested for function assessment and further evaluated using five able-bodied subjects for user feedback. The ROWAS prototype produced coordinated performance in the upper and lower limbs, with joint profiles similar to those occurring in normal gait. The subjects reported a stronger feeling of walking with arm swing than without. The ROWAS system was deemed feasible according to the formal assessment criteria. PMID:28203142

Urine trouble: a social history of bedwetting and its regulation.

PubMed

Hurl, Chris

2011-01-01

Bedwetting has confounded the presumed boundaries of the human body, existing in a fluid space, between the normal and pathological, its treatment has demanded the application of a wide array of different technologies, each based on a distinct conception of the relationship between the body and personality, human organs and personal conduct. In tracing the social history of bedwetting and its regulation, this article examines the ontological assumptions underpinning the treatment of bedwetting and how they have changed over the past two centuries. Through the analysis of medical journals, newspaper articles and magazine advertisements, different topologies are identified which redefine the boundaries of the human body and its capacities. From 16th-century naturalism, in which the human body is subordinated to a cosmic totality, to the circumscribed space of 19th-century paediatrics and the expansive circuits of behavioural psychology and modern psychoanalysis, the body has become multiplied, differently enacted through the application of diverse technologies. It was be shown how coordinating the messy and divergent conceptions of the human body has posed an endemic problem for the human sciences, and how the enduring tension between object enactment and subject constitution is an expression of modern "baroque" subjectivity.

The impact of systemic cortical alterations on perception

NASA Astrophysics Data System (ADS)

Zhang, Zheng

2011-12-01

Perception is the process of transmitting and interpreting sensory information, and the primary somatosensory (SI) area in the human cortex is the main sensory receptive area for the sensation of touch. The elaborate neuroanatomical connectivity that subserves the neuronal communication between adjacent and near-adjacent regions within sensory cortex has been widely recognized to be essential to normal sensory function. As a result, systemic cortical alterations that impact the cortical regional interaction, as associated with many neurological disorders, are expected to have significant impact on sensory perception. Recently, our research group has developed a novel sensory diagnostic system that employs quantitative sensory testing methods and is able to non-invasively assess central nervous system healthy status. The intent of this study is to utilize quantitative sensory testing methods that were designed to generate discriminable perception to objectively and quantitatively assess the impacts of different conditions on human sensory information processing capacity. The correlation between human perceptions with observations from animal research enables a better understanding of the underlying neurophysiology of human perception. Additional findings on different subject populations provide valuable insight of the underlying mechanisms for the development and maintenance of different neurological diseases. During the course of the study, several protocols were designed and utilized. And this set of sensory-based perceptual metrics was employed to study the effects of different conditions (non-noxious thermal stimulation, chronic pain stage, and normal aging) on sensory perception. It was found that these conditions result in significant deviations of the subjects' tactile information processing capacities from normal values. Although the observed shift of sensory detection sensitivity could be a result of enhanced peripheral activity, the changes in the effects of adaptation most likely reflect changes in central nervous system. The findings in this work provide valuable information for better understanding the underlying mechanisms involved in the development and maintenance of different neurological conditions.

Calcium orthophosphates

PubMed Central

Dorozhkin, Sergey V.

2011-01-01

The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates. This type of materials is of special significance for human beings, because they represent the inorganic part of major normal (bones, teeth and antlers) and pathological (i.e., those appearing due to various diseases) calcified tissues of mammals. For example, atherosclerosis results in blood vessel blockage caused by a solid composite of cholesterol with calcium orthophosphates, while dental caries and osteoporosis mean a partial decalcification of teeth and bones, respectively, that results in replacement of a less soluble and harder biological apatite by more soluble and softer calcium hydrogenphosphates. Therefore, the processes of both normal and pathological calcifications are just an in vivo crystallization of calcium orthophosphates. Similarly, dental caries and osteoporosis might be considered an in vivo dissolution of calcium orthophosphates. Thus, calcium orthophosphates hold a great significance for humankind, and in this paper, an overview on the current knowledge on this subject is provided. PMID:23507744

Brain Biochemistry and Personality: A Magnetic Resonance Spectroscopy Study

PubMed Central

Ryman, Sephira G.; Gasparovic, Chuck; Bedrick, Edward J.; Flores, Ranee A.; Marshall, Alison N.; Jung, Rex E.

2011-01-01

To investigate the biochemical correlates of normal personality we utilized proton magnetic resonance spectroscopy (1H-MRS). Our sample consisted of 60 subjects ranging in age from 18 to 32 (27 females). Personality was assessed with the NEO Five-Factor Inventory (NEO-FFI). We measured brain biochemistry within the precuneus, the cingulate cortex, and underlying white matter. We hypothesized that brain biochemistry within these regions would predict individual differences across major domains of personality functioning. Biochemical models were fit for all personality domains including Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness. Our findings involved differing concentrations of Choline (Cho), Creatine (Cre), and N-acetylaspartate (NAA) in regions both within (i.e., posterior cingulate cortex) and white matter underlying (i.e., precuneus) the Default Mode Network (DMN). These results add to an emerging literature regarding personality neuroscience, and implicate biochemical integrity within the default mode network as constraining major personality domains within normal human subjects. PMID:22073190

Effect of mental stress on plasma homovanillic acid in healthy human subjects.

PubMed

Sumiyoshi, T; Yotsutsuji, T; Kurachi, M; Itoh, H; Kurokawa, K; Saitoh, O

1998-07-01

Plasma levels of homovanillic acid (pHVA) have been suggested to provide a measure of dopaminergic activity in the central nervous system. The present study investigated the effect of mental stress by the Kraepelin test, a test of continuous arithmetic addition of single-digit figures for 30 min, on pHVA levels in 13 male psychiatrically normal healthy volunteers. Following an overnight fast and restricted physical activity, plasma samples were collected immediately before and after the administration of the Kraepelin test. Plasma HVA levels following the administration of the Kraepelin test were significantly lower than the pretest pHVA levels. The percent change in pHVA levels by the Kraepelin test positively correlated with pretest pHVA levels. The observed reduction in pHVA levels by mental stress in normal subjects may reflect some aspects of a dopamine-dependent restitutive system in the brain.

Recycling energy to restore impaired ankle function during human walking.

PubMed

Collins, Steven H; Kuo, Arthur D

2010-02-17

Humans normally dissipate significant energy during walking, largely at the transitions between steps. The ankle then acts to restore energy during push-off, which may be the reason that ankle impairment nearly always leads to poorer walking economy. The replacement of lost energy is necessary for steady gait, in which mechanical energy is constant on average, external dissipation is negligible, and no net work is performed over a stride. However, dissipation and replacement by muscles might not be necessary if energy were instead captured and reused by an assistive device. We developed a microprocessor-controlled artificial foot that captures some of the energy that is normally dissipated by the leg and "recycles" it as positive ankle work. In tests on subjects walking with an artificially-impaired ankle, a conventional prosthesis reduced ankle push-off work and increased net metabolic energy expenditure by 23% compared to normal walking. Energy recycling restored ankle push-off to normal and reduced the net metabolic energy penalty to 14%. These results suggest that reduced ankle push-off contributes to the increased metabolic energy expenditure accompanying ankle impairments, and demonstrate that energy recycling can be used to reduce such cost.

Cue-dependent memory-based smooth-pursuit in normal human subjects: importance of extra-retinal mechanisms for initial pursuit.

PubMed

Ito, Norie; Barnes, Graham R; Fukushima, Junko; Fukushima, Kikuro; Warabi, Tateo

2013-08-01

Using a cue-dependent memory-based smooth-pursuit task previously applied to monkeys, we examined the effects of visual motion-memory on smooth-pursuit eye movements in normal human subjects and compared the results with those of the trained monkeys. These results were also compared with those during simple ramp-pursuit that did not require visual motion-memory. During memory-based pursuit, all subjects exhibited virtually no errors in either pursuit-direction or go/no-go selection. Tracking eye movements of humans and monkeys were similar in the two tasks, but tracking eye movements were different between the two tasks; latencies of the pursuit and corrective saccades were prolonged, initial pursuit eye velocity and acceleration were lower, peak velocities were lower, and time to reach peak velocities lengthened during memory-based pursuit. These characteristics were similar to anticipatory pursuit initiated by extra-retinal components during the initial extinction task of Barnes and Collins (J Neurophysiol 100:1135-1146, 2008b). We suggest that the differences between the two tasks reflect differences between the contribution of extra-retinal and retinal components. This interpretation is supported by two further studies: (1) during popping out of the correct spot to enhance retinal image-motion inputs during memory-based pursuit, pursuit eye velocities approached those during simple ramp-pursuit, and (2) during initial blanking of spot motion during memory-based pursuit, pursuit components appeared in the correct direction. Our results showed the importance of extra-retinal mechanisms for initial pursuit during memory-based pursuit, which include priming effects and extra-retinal drive components. Comparison with monkey studies on neuronal responses and model analysis suggested possible pathways for the extra-retinal mechanisms.

Effect of voluntary hypocapnic hyperventilation on cutaneous circulation in resting heated humans.

PubMed

Fujii, Naoto; Honda, Yasushi; Delliaux, Stephane; Tsuji, Bun; Watanabe, Kazuhito; Sugihara, Akira; Kondo, Narihiko; Nishiyasu, Takeshi

2012-11-01

Hypocapnia attenuates the sweat response normally seen in hyperthermic resting subjects, but its effect on the blood flow response in their nonglabrous skin under the same hyperthermic conditions remains unclear. In the present study, we investigated whether hypocapnia induced by voluntary hyperventilation affects the blood flow response to heat stress in the nonglabrous skin of resting humans. Nine healthy male subjects were passively heated using legs-only hot water immersion and a water-perfused suit, which caused esophageal temperature (T(es)) to increase by as much as 1.0°C. During normothermia and at +0.6°C T(es) and +1.0°C T(es), the subjects performed two voluntary 7-min hyperventilation (minute ventilation = 40 l/min) trials (hypocapnic and eucapnic) in random order. End-tidal CO(2) pressure was reduced by 23-25 torr during hypocapnic hyperventilation, but it was maintained at the spontaneous breathing level during eucapnic hyperventilation. Cutaneous blood flow was evaluated as the cutaneous red blood cell flux in the forearm (CBF(forearm)) or forehead (CBF(forehead)) and was normalized to the normothermic spontaneous breathing value. Hypocapnic hyperventilation at +0.6°C T(es) was associated with significantly reduced CBF(forearm), compared with eucapnic hyperventilation, after 5-7 min of hyperventilation (395 to 429 vs. 487 to 525% baseline, P < 0.05). No significant difference in CBF(forehead) was seen during hypocapnic hyperventilation compared with eucapnic hyperventilation at +0.6°C T(es) or +1.0°C T(es). These results suggest that in resting humans, hypocapnia achieved through voluntary hyperventilation attenuates the increase in cutaneous blood flow elicited by moderate heat stress in the nonglabrous skin of the forearm, but not the forehead.

Obesity changes the human gut mycobiome

PubMed Central

Mar Rodríguez, M.; Pérez, Daniel; Javier Chaves, Felipe; Esteve, Eduardo; Marin-Garcia, Pablo; Xifra, Gemma; Vendrell, Joan; Jové, Mariona; Pamplona, Reinald; Ricart, Wifredo; Portero-Otin, Manuel; Chacón, Matilde R.; Fernández Real, José Manuel

2015-01-01

The human intestine is home to a diverse range of bacterial and fungal species, forming an ecological community that contributes to normal physiology and disease susceptibility. Here, the fungal microbiota (mycobiome) in obese and non-obese subjects was characterized using Internal Transcribed Spacer (ITS)-based sequencing. The results demonstrate that obese patients could be discriminated by their specific fungal composition, which also distinguished metabolically “healthy” from “unhealthy” obesity. Clusters according to genus abundance co-segregated with body fatness, fasting triglycerides and HDL-cholesterol. A preliminary link to metabolites such as hexadecanedioic acid, caproic acid and N-acetyl-L-glutamic acid was also found. Mucor racemosus and M. fuscus were the species more represented in non-obese subjects compared to obese counterparts. Interestingly, the decreased relative abundance of the Mucor genus in obese subjects was reversible upon weight loss. Collectively, these findings suggest that manipulation of gut mycobiome communities might be a novel target in the treatment of obesity. PMID:26455903

Mapping population-based structural connectomes.

PubMed

Zhang, Zhengwu; Descoteaux, Maxime; Zhang, Jingwen; Girard, Gabriel; Chamberland, Maxime; Dunson, David; Srivastava, Anuj; Zhu, Hongtu

2018-05-15

Advances in understanding the structural connectomes of human brain require improved approaches for the construction, comparison and integration of high-dimensional whole-brain tractography data from a large number of individuals. This article develops a population-based structural connectome (PSC) mapping framework to address these challenges. PSC simultaneously characterizes a large number of white matter bundles within and across different subjects by registering different subjects' brains based on coarse cortical parcellations, compressing the bundles of each connection, and extracting novel connection weights. A robust tractography algorithm and streamline post-processing techniques, including dilation of gray matter regions, streamline cutting, and outlier streamline removal are applied to improve the robustness of the extracted structural connectomes. The developed PSC framework can be used to reproducibly extract binary networks, weighted networks and streamline-based brain connectomes. We apply the PSC to Human Connectome Project data to illustrate its application in characterizing normal variations and heritability of structural connectomes in healthy subjects. Copyright © 2018 Elsevier Inc. All rights reserved.

“Ready-to-Recruit” or “Ready-to-Consent” Populations?: Informed Consent and the Limits of Subject Autonomy

PubMed Central

Fisher, Jill A.

2011-01-01

This paper queries the pharmaceutical industry’s concept of “ready-to-recruit” populations by examining its recruitment strategies for clinical trials and the types of human subjects who participate in these drug studies. The argument is that the pharmaceutical industry has profited from a system comprised of what can more aptly be characterized as ready-to-consent populations, meaning populations who do not have better alternatives than participation in clinical trials. Further, through qualitative research, this paper aims to highlight some of the limitations of current U.S. federal regulation and to show how these limits signal problems that are not normally discussed in the medical ethics literature about research on human subjects. It does this by examining the impotence of informed consent – both as a concept and as a practice – in light of recruitment strategies and the structural reasons motivating individuals to participate in clinical trials. PMID:21359125

Optimizing cryopreservation of human spermatogonial stem cells: comparing the effectiveness of testicular tissue and single cell suspension cryopreservation

PubMed Central

Yango, Pamela; Altman, Eran; Smith, James F.; Klatsky, Peter C.; Tran, Nam D.

2015-01-01

Objective To determine whether optimal human spermatogonial stem cell (SSC) cryopreservation is best achieved with testicular tissue or single cell suspension cryopreservation. This study compares the effectiveness between these two approaches by using testicular SSEA-4+ cells, a known population containing SSCs. Design In vitro human testicular tissues. Setting Academic research unit. Patients Adult testicular tissues (n = 4) collected from subjects with normal spermatogenesis and normal fetal testicular tissues (n = 3). Intervention(s) Testicular tissue vs. single cell suspension cryopreservation. Main Outcome Measures Cell viability, total cell recovery per milligram of tissue, as well as, viable and SSEA-4+ cell recovery. Results Single cell suspension cryopreservation yielded higher recovery of SSEA-4+ cells enriched in adult SSCs whereas fetal SSEA-4+ cell recovery was similar between testicular tissue and single cell suspension cryopreservation. Conclusions Adult and fetal human SSEA-4+ populations exhibited differential sensitivity to cryopreservation based on whether they were cryopreserved in situ as testicular tissues or as single cells. Thus, optimal preservation of human SSCs depends on the patient age, type of samples cryopreserved, and end points of therapeutic applications. PMID:25241367

Is MMTV associated with human breast cancer? Maybe, but probably not.

PubMed

Perzova, Raisa; Abbott, Lynn; Benz, Patricia; Landas, Steve; Khan, Seema; Glaser, Jordan; Cunningham, Coleen K; Poiesz, Bernard

2017-10-13

Conflicting results regarding the association of MMTV with human breast cancer have been reported. Published sequence data have indicated unique MMTV strains in some human samples. However, concerns regarding contamination as a cause of false positive results have persisted. We performed PCR assays for MMTV on human breast cancer cell lines and fresh frozen and formalin fixed normal and malignant human breast epithelial samples. Assays were also performed on peripheral blood mononuclear cells from volunteer blood donors and subjects at risk for human retroviral infections. In addition, assays were performed on DNA samples from wild and laboratory mice. Sequencing of MMTV positive samples from both humans and mice were performed and phylogenetically compared. Using PCR under rigorous conditions to prevent and detect "carryover" contamination, we did detect MMTV DNA in human samples, including breast cancer. However, the results were not consistent and seemed to be an artifact. Further, experiments indicated that the probable source of false positives was murine DNA, containing endogenous MMTV, present in our building. However, comparison of published and, herein, newly described MMTV sequences with published data, indicates that there are some very unique human MMTV sequences in the literature. While we could not confirm the true presence of MMTV in our human breast cancer subjects, the data indicate that further, perhaps more traditional, retroviral studies are warranted to ascertain whether MMTV might rarely be the cause of human breast cancer.

The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age.

PubMed

Trabado, Séverine; Al-Salameh, Abdallah; Croixmarie, Vincent; Masson, Perrine; Corruble, Emmanuelle; Fève, Bruno; Colle, Romain; Ripoll, Laurent; Walther, Bernard; Boursier-Neyret, Claire; Werner, Erwan; Becquemont, Laurent; Chanson, Philippe

2017-01-01

Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the "normal" metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the "normal" metabolome and its main sources of variation.

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

Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena

Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical datamore » have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.« less

Changes in Ultrastructure and Cytoskeletal Aspects of Human Normal and Osteoarthritic Chondrocytes Exposed to Interleukin-1β and Cyclical Hydrostatic Pressure.

PubMed

Pascarelli, Nicola Antonio; Collodel, Giulia; Moretti, Elena; Cheleschi, Sara; Fioravanti, Antonella

2015-10-30

The aim of this study was to examine the ultrastructure and cytoskeletal organization in human normal and Osteoarhritic (OA) chondrocytes, exposed to interleukin-1β (IL-1β) and cyclic hydrostatic pressure (HP). Morphological examination by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed differences between normal and OA chondrocytes at the nuclear and cytoplasmic level. IL-1β (5 ng/mL) induced a decrease of the number of mitochondria and Golgi bodies and a significant increase on the percentage of cells rich in vacuolization and in marginated chromatin. Cyclical HP (1-5 MPa, 0.25 Hz, for 3 h) did not change the morphology of normal chondrocytes, but had a beneficial effect on OA chondrocytes increasing the number of organelles. Normal and OA cells subjected to IL-1β and HP recovered cytoplasmic ultrastructure. Immunofluorescence (IF) examination of normal chondrocytes showed an actin signal polarized on the apical sides of the cytoplasm, tubulin and vimentin uniformly distributed throughout cytoplasm and vinculin revealed a punctuated pattern under the plasma membrane. In OA chondrocytes, these proteins partially lost their organization. Stimulation with IL-1β caused, in both type of cells, modification in the cytoskeletal organization; HP counteracted the negative effects of IL-1β. Our results showed structural differences at nuclear, cytoplasmic and cytoskeletal level between normal and OA chondrocytes. IL-1β induced ultrastructural and cytoskeletal modifications, counteracted by a cyclical low HP.

Changes in Ultrastructure and Cytoskeletal Aspects of Human Normal and Osteoarthritic Chondrocytes Exposed to Interleukin-1β and Cyclical Hydrostatic Pressure

PubMed Central

Pascarelli, Nicola Antonio; Collodel, Giulia; Moretti, Elena; Cheleschi, Sara; Fioravanti, Antonella

2015-01-01

The aim of this study was to examine the ultrastructure and cytoskeletal organization in human normal and Osteoarhritic (OA) chondrocytes, exposed to interleukin-1β (IL-1β) and cyclic hydrostatic pressure (HP). Morphological examination by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed differences between normal and OA chondrocytes at the nuclear and cytoplasmic level. IL-1β (5 ng/mL) induced a decrease of the number of mitochondria and Golgi bodies and a significant increase on the percentage of cells rich in vacuolization and in marginated chromatin. Cyclical HP (1–5 MPa, 0.25 Hz, for 3 h) did not change the morphology of normal chondrocytes, but had a beneficial effect on OA chondrocytes increasing the number of organelles. Normal and OA cells subjected to IL-1β and HP recovered cytoplasmic ultrastructure. Immunofluorescence (IF) examination of normal chondrocytes showed an actin signal polarized on the apical sides of the cytoplasm, tubulin and vimentin uniformly distributed throughout cytoplasm and vinculin revealed a punctuated pattern under the plasma membrane. In OA chondrocytes, these proteins partially lost their organization. Stimulation with IL-1β caused, in both type of cells, modification in the cytoskeletal organization; HP counteracted the negative effects of IL-1β. Our results showed structural differences at nuclear, cytoplasmic and cytoskeletal level between normal and OA chondrocytes. IL-1β induced ultrastructural and cytoskeletal modifications, counteracted by a cyclical low HP. PMID:26528971

The Complexity of Human Walking: A Knee Osteoarthritis Study

PubMed Central

Kotti, Margarita; Duffell, Lynsey D.; Faisal, Aldo A.; McGregor, Alison H.

2014-01-01

This study proposes a framework for deconstructing complex walking patterns to create a simple principal component space before checking whether the projection to this space is suitable for identifying changes from the normality. We focus on knee osteoarthritis, the most common knee joint disease and the second leading cause of disability. Knee osteoarthritis affects over 250 million people worldwide. The motivation for projecting the highly dimensional movements to a lower dimensional and simpler space is our belief that motor behaviour can be understood by identifying a simplicity via projection to a low principal component space, which may reflect upon the underlying mechanism. To study this, we recruited 180 subjects, 47 of which reported that they had knee osteoarthritis. They were asked to walk several times along a walkway equipped with two force plates that capture their ground reaction forces along 3 axes, namely vertical, anterior-posterior, and medio-lateral, at 1000 Hz. Data when the subject does not clearly strike the force plate were excluded, leaving 1–3 gait cycles per subject. To examine the complexity of human walking, we applied dimensionality reduction via Probabilistic Principal Component Analysis. The first principal component explains 34% of the variance in the data, whereas over 80% of the variance is explained by 8 principal components or more. This proves the complexity of the underlying structure of the ground reaction forces. To examine if our musculoskeletal system generates movements that are distinguishable between normal and pathological subjects in a low dimensional principal component space, we applied a Bayes classifier. For the tested cross-validated, subject-independent experimental protocol, the classification accuracy equals 82.62%. Also, a novel complexity measure is proposed, which can be used as an objective index to facilitate clinical decision making. This measure proves that knee osteoarthritis subjects exhibit more variability in the two-dimensional principal component space. PMID:25232949

Real-Time Classification of Patients with Balance Disorders vs. Normal Subjects Using a Low-Cost Small Wireless Wearable Gait Sensor.

PubMed

Nukala, Bhargava Teja; Nakano, Taro; Rodriguez, Amanda; Tsay, Jerry; Lopez, Jerry; Nguyen, Tam Q; Zupancic, Steven; Lie, Donald Y C

2016-11-29

Gait analysis using wearable wireless sensors can be an economical, convenient and effective way to provide diagnostic and clinical information for various health-related issues. In this work, our custom designed low-cost wireless gait analysis sensor that contains a basic inertial measurement unit (IMU) was used to collect the gait data for four patients diagnosed with balance disorders and additionally three normal subjects, each performing the Dynamic Gait Index (DGI) tests while wearing the custom wireless gait analysis sensor (WGAS). The small WGAS includes a tri-axial accelerometer integrated circuit (IC), two gyroscopes ICs and a Texas Instruments (TI) MSP430 microcontroller and is worn by each subject at the T4 position during the DGI tests. The raw gait data are wirelessly transmitted from the WGAS to a near-by PC for real-time gait data collection and analysis. In order to perform successful classification of patients vs. normal subjects, we used several different classification algorithms, such as the back propagation artificial neural network (BP-ANN), support vector machine (SVM), k -nearest neighbors (KNN) and binary decision trees (BDT), based on features extracted from the raw gait data of the gyroscopes and accelerometers. When the range was used as the input feature, the overall classification accuracy obtained is 100% with BP-ANN, 98% with SVM, 96% with KNN and 94% using BDT. Similar high classification accuracy results were also achieved when the standard deviation or other values were used as input features to these classifiers. These results show that gait data collected from our very low-cost wearable wireless gait sensor can effectively differentiate patients with balance disorders from normal subjects in real time using various classifiers, the success of which may eventually lead to accurate and objective diagnosis of abnormal human gaits and their underlying etiologies in the future, as more patient data are being collected.

Patellar maltracking is prevalent among patellofemoral pain subjects with patella alta: an upright, weightbearing MRI study

PubMed Central

Pal, Saikat; Besier, Thor F.; Beaupre, Gary S.; Fredericson, Michael; Delp, Scott L.; Gold, Garry E.

2012-01-01

The purpose of this study is to determine if patellar maltracking is more prevalent among patellofemoral (PF) pain subjects with patella alta compared to subjects with normal patella height. We imaged 37 PF pain and 15 pain free subjects in an open-configuration magnetic resonance imaging scanner while they stood in a weightbearing posture. We measured patella height using the Caton-Deschamps, Blackburne-Peel, Insall-Salvati, Modified Insall-Salvati, and Patellotrochlear indices, and classified the subjects into patella alta and normal patella height groups. We measured patella tilt and bisect offset from oblique-axial plane images, and classified the subjects into maltracking and normal tracking groups. Patellar maltracking was more prevalent among PF pain subjects with patella alta compared to PF pain subjects with normal patella height (two-tailed Fisher’s exact test, p < 0.050). Using the Caton-Deschamps index, 67% (8/12) of PF pain subjects with patella alta were maltrackers, whereas only 16% (4/25) of PF pain subjects with normal patella height were maltrackers. Patellofemoral pain subjects classified as maltrackers displayed a greater patella height compared to the pain free and PF pain subjects classified as normal trackers (two-tailed unpaired t-tests with Bonferroni correction, p < 0.017). This study adds to our understanding of PF pain in two ways - 1) we demonstrate that patellar maltracking is more prevalent in PF pain subjects with patella alta compared to subjects with normal patella height; and 2) we show greater patella height in PF pain subjects compared to pain free subjects using four indices commonly used in clinics. PMID:23165335

Effects of income on drug choice in humans.

PubMed Central

DeGrandpre, R J; Bickel, W K; Rizvi, S A; Hughes, J R

1993-01-01

The effects of income (money available to spend during the experimental session) on human choice were examined in a concurrent-schedule arrangement. Subjects were 7 nicotine-dependent smokers, and reinforcers were puffs on the subject's usual brand of cigarette ("own") and puffs on a less preferred brand of cigarette with equal nicotine content ("other"). Across sessions, income varied and the price of the two reinforcers was held constant, with the other puffs one fifth the price of the own puffs. As income increased, consumption of own puffs increased while consumption of the less expensive other puffs decreased. These effects of income on choice were highly consistent across subjects. For some subjects, however, income had little effect on total puff consumption. Finally, an additional condition examined whether price and income manipulations would have functionally equivalent effects on choice by repeating an income condition in which the price of the other brand was increased. Although the increased price of the other puffs decreased their consumption in 4 subjects, 2 subjects showed increased consumption of the other puffs at the higher price. The results, when defined in economic terms, indicate that the own puffs were a normal good (consumption and income are directly related), the other puffs were an inferior good (consumption and income are inversely related), and the direct relationship between consumption of the other puffs and their price is defined as a Giffengood effect. The latter result also suggests that for these 2 subjects, price and income manipulations had equivalent effects on choice. These results extend findings from previous studies that have examined the effects of income on choice responding to human subjects and drug reinforcers, and provide a framework for further experimental tests of the effects of income on human choice behavior. Methodological and theoretical implications for the study of choice and for behavioral pharmacology are discussed. PMID:8315366

Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans.

PubMed

Cedernaes, Jonathan; Fanelli, Flaminia; Fazzini, Alessia; Pagotto, Uberto; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Schiöth, Helgi B; Benedict, Christian

2016-12-01

Following binding to cannabinoid receptors, endocannabinoids regulate a variety of central nervous system processes including appetite and mood. Recent evidence suggests that the systemic release of these lipid metabolites can be altered by acute exercise and that their levels also vary across the 24-h sleep-wake cycle. The present study utilized a within-subject design (involving 16 normal-weight men) to determine whether daytime circulating endocannabinoid concentrations differ following three nights of partial sleep deprivation (4.25-h sleep opportunity, 2:45-7a.m. each night) vs. normal sleep (8.5-h sleep opportunity, 10:30p.m.-7a.m. each night), before and after an acute bout of ergometer cycling in the morning. In addition, subjective hunger and stress were measured. Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5h after awakening (vs. normal sleep, p<0.05) when participants were sleep-deprived. This coincided with increased hunger ratings (+25% vs. normal sleep, p<0.05). Moreover, plasma 2AG was elevated 15min post-exercise (+44%, p<0.05). Sleep duration did not however modulate this exercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (p<0.05). Given that activation of the endocannabinoid system has been previously shown to acutely increase appetite and mood, our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway. In contrast, more pronounced exercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Proton spectroscopy in the narcoleptic syndrome. Is there evidence of a brainstem lesion?

PubMed

Ellis, C M; Simmons, A; Lemmens, G; Williams, S C; Parkes, J D

1998-02-01

There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome.

Metabolic Studies in Military Nutrition.

DTIC Science & Technology

1977-05-01

The Surgeon General’s Office over a period of years has undertaken an extensive research program into the chemistry, nutrition , and wholesomeness of...Research and Nutrition Laboratory has undertaken the studies of the wholesomeness of food preserved by ionizing radiation. Work on radiated food has been...physiological, metabolic, and nutritional research in normal young adult men has been going on making use of volunteer human test subjects.

Angiotensin-converting enzyme activity and cognitive impairment during hypoglycaemia in healthy humans.

PubMed

Pedersen-Bjergaard, Ulrik; Thomsen, Carsten E; Høgenhaven, Hans; Smed, Annelise; Kjaer, Troels W; Holst, Jens J; Dela, Flemming; Hilsted, Linda; Frandsen, Erik; Pramming, Stig; Thorsteinsson, Birger

2008-03-01

In type 1 diabetes increased risk of severe hypoglycaemia is associated with high angiotensin-converting enzyme (ACE) activity. We tested in healthy humans the hypothesis that this association is explained by the reduced ability of subjects with high ACE activity to maintain normal cognitive function during hypoglycaemia. Sixteen healthy volunteers selected by either particularly high or low serum ACE activity were subjected to hypoglycaemia (plasma glucose 2.7 mmol/L). Cognitive function was assessed by choice reaction tests. Despite a similar hypoglycaemic stimulus in the two groups, only the group with high ACE activity showed significant deterioration in cognitive performance during hypoglycaemia. In the high ACE group mean reaction time (MRT) in the most complex choice reaction task was prolonged and error rate (ER) was increased in contrast to the low ACE group. The total hypoglycaemic symptom response was greater in the high ACE group than in the low ACE group (p=0.031). There were no differences in responses of counterregulatory hormones or in concentrations of substrates between the groups. Healthy humans with high ACE activity are more susceptible to cognitive dysfunction and report higher symptom scores during mild hypoglycaemia than subjects with low ACE activity.

Plasma Shh levels reduced in pancreatic cancer patients.

PubMed

El-Zaatari, Mohamad; Daignault, Stephanie; Tessier, Art; Kelsey, Gail; Travnikar, Lisa A; Cantu, Esperanza F; Lee, Jamie; Plonka, Caitlyn M; Simeone, Diane M; Anderson, Michelle A; Merchant, Juanita L

2012-10-01

Normally, sonic hedgehog (Shh) is expressed in the pancreas during fetal development and transiently after tissue injury. Although pancreatic cancers express Shh, it is not known if the protein is secreted into the blood and whether its plasma levels change with pancreatic transformation. The goal of this study was to develop an enzyme-linked immunosorbent assay to detect human Shh in blood and determine its levels in subjects with and without pancreatic cancer. A human Shh enzyme-linked immunosorbent assay was developed, and plasma Shh levels were measured in blood samples from healthy subjects and patients with pancreatitis or pancreatic cancer. The biological activity of plasma Shh was tested using NIH-3T3 cells. The mean levels of Shh in human blood were lower in patients with pancreatitis and pancreatic cancer than in healthy subjects. Hematopoietic cells did not express Shh, suggesting that Shh is secreted into the bloodstream. Plasma fractions enriched with Shh did not induce Gli-1 messenger RNA, suggesting that the protein was not biologically active. Shh is secreted from tissues and organs into the circulation, but its activity is blocked by plasma proteins. Reduced plasma levels were found in pancreatic cancer patients, but alone were not sufficient to predict pancreatic cancer.

The effect of chromium picolinate on serum cholesterol and apolipoprotein fractions in human subjects.

PubMed Central

Press, R. I.; Geller, J.; Evans, G. W.

1990-01-01

Chromium has been implicated as a cofactor in the maintenance of normal lipid and carbohydrate metabolism. A deficiency of chromium results from diets low in biologically available chromium. Picolinic acid, a metabolite of tryptophan, forms stable complexes with transitional metal ions, which results in an improved bioavailability of the metal ion chromium. To determine whether or not chromium picolinate is effective in humans, 28 volunteer subjects were given either chromium tripicolinate (3.8 micromol [200 micrograms] chromium) or a placebo daily for 42 days in a double-blind crossover study. A 14-day period off capsules was used between treatments. Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B, the principal protein of the LDL fraction, decreased significantly while the subjects were ingesting chromium picolinate. The concentration of apolipoprotein A-I, the principal protein of the high-density lipoprotein (HDL) fraction, increased substantially during treatment with chromium picolinate. The HDL-cholesterol level was elevated slightly but not significantly during ingestion of chromium picolinate. Only apolipoprotein B, of the variables measured, was altered significantly during supplementation with the placebo. These observations show that chromium picolinate is efficacious in lowering blood lipids in humans. PMID:2408233

Human osteopontin splicing isoforms: known roles, potential clinical applications and activated signaling pathways.

PubMed

Gimba, E R; Tilli, T M

2013-04-30

Human osteopontin is subject to alternative splicing, which generates three isoforms, termed OPNa, OPNb and OPNc. These variants show specific expression and roles in different cell contexts. We present an overview of current knowledge of the expression profile of human OPN splicing isoforms (OPN-SIs), their tissue-specific roles, and the pathways mediating their functional properties in different pathophysiological conditions. We also describe their putative application as biomarkers, and their potential use as therapeutic targets by using antibodies, oligonucleotides or siRNA molecules. This synthesis provides new clues for a better understanding of human OPN splice variants, their roles in normal and pathological conditions, and their possible clinical applications. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Balancing justice and autonomy in clinical research with healthy volunteers.

PubMed

Kass, N E; Myers, R; Fuchs, E J; Carson, K A; Flexner, C

2007-08-01

In clinical research, ethics review generally first examines whether study risks are reasonable in light of benefits provided. Through informed consent, then, prospective subjects consider whether the risk/benefit balance and procedures are reasonable for them. Unique ethics issues emerge in clinical research with healthy volunteers. Certain types of studies only recruit healthy volunteers as participants. Phase 1 studies, for example, including first time in human studies of investigational drugs and vaccines, generally are conducted in healthy volunteers. Although such research carries inherent and often unknown risks, healthy subjects provide the most efficient target population in which to conduct such research, as these volunteers generally are free of concurrent diseases or medications that could confound interpretation of toxicity. Other studies enrolling healthy volunteers often are simply looking for the most scientifically sound population for the study of normal human physiology.

Eyes open versus eyes closed - Effect on human rotational responses

NASA Technical Reports Server (NTRS)

Wall, Conrad, III; Furman, Joseph M. R.

1989-01-01

The effect of eyelid closure on the response to rotational vestibular stimulation was assessed by evaluating 16 normal human subjects with both earth vertical axis (EVA) and earth horizontal axis (EHA) yaw rotations with either eyes closed (EC) or eyes open in the dark (EOD). Results indicated that for EVA rotation, the subjects' responses were of larger magnitude and less variable with EOD than with EC. However, for EHA rotation, responses were of larger magnitude and equally variable with EC as compared to EOD. Data also indicated that the quality of the EHA response with EC was altered because eyelid closure influenced the amount of periodic gaze. It is concluded that eyelid closure has an effect upon both canalocular and otolithocular reflexes and it is suggested that both EVA and EHA rotational testing be performed with EOD rather than with EC.

[Emotional response to music by postlingually-deafened adult cochlear implant users].

PubMed

Wang, Shuo; Dong, Ruijuan; Zhou, Yun; Li, Jing; Qi, Beier; Liu, Bo

2012-10-01

To assess the emotional response to music by postlingually-deafened adult cochlear implant users. Munich music questionnaire (MUMU) was used to match the music experience and the motivation of use of music between 12 normal-hearing and 12 cochlear implant subjects. Emotion rating test in Musical Sounds in Cochlear Implants (MuSIC) test battery was used to assess the emotion perception ability for both normal-hearing and cochlear implant subjects. A total of 15 pieces of music phases were used. Responses were given by selecting the rating scales from 1 to 10. "1" represents "very sad" feeling, and "10" represents "very happy feeling. In comparison with normal-hearing subjects, 12 cochlear implant subjects made less active use of music for emotional purpose. The emotion ratings for cochlear implant subjects were similar to normal-hearing subjects, but with large variability. Post-lingually deafened cochlear implant subjects on average performed similarly in emotion rating tasks relative to normal-hearing subjects, but their active use of music for emotional purpose was obviously less than normal-hearing subjects.

Cortical NMDA receptor expression in human chronic alcoholism: influence of the TaqIA allele of ANKK1.

PubMed

Ridge, Justin P; Dodd, Peter R

2009-10-01

Real-time RT-PCR normalized to GAPDH was used to assay N-methyl-D-aspartate (NMDA) receptor NR1, NR2A and NR2B subunit mRNA in human autopsy cortex tissue from chronic alcoholics with and without comorbid cirrhosis of the liver and matched controls. Subunit expression was influenced by the subject's genotype. The TaqIA polymorphism selectively modulated NMDA receptor mean transcript expression in cirrhotic-alcoholic superior frontal cortex, in diametrically opposite ways in male and female subjects. Genetic make-up may differentially influence vulnerability to brain damage by altering the excitation: inhibition balance, particularly in alcoholics with comorbid cirrhosis of the liver. The TaqIA polymorphism occurs within the poorly characterised ankyrin-repeat containing kinase 1 (ANKK1) gene. Using PCR, ANKK1 mRNA transcript was detected in inferior temporal, occipital, superior frontal and primary motor cortex of control human brain. ANKK1 expression may mediate the influence of the TaqIA polymorphism on phenotype.

Effects of Local Compression on Peroneal Nerve Function in Humans

NASA Technical Reports Server (NTRS)

Hargens, Alan R.; Botte, Michael J.; Swenson, Michael R.; Gelberman, Richard H.; Rhoades, Charles E.; Akeson, Wayne H.

1993-01-01

A new apparatus was developed to compress the anterior compartment selectively and reproducibly in humans. Thirty-five normal volunteers were studied to determine short-term thresholds of local tissue pressure that produce significant neuromuscular dysfunction. Local tissue fluid pressure adjacent to the deep peroneal nerve was elevated by the compression apparatus and continuously monitored for 2-3 h by the slit catheter technique. Elevation of tissue fluid pressure to within 35-40 mm Hg of diastolic blood pressure (approx. 40 mm Hg of in situ pressure in our subjects) elicited a consistent progression of neuromuscular deterioration including, in order, (a) gradual loss of sensation, as assessed by Semmes-Weinstein monofilaments, (b) subjective complaints, (c) reduced nerve conduction velocity, (d) decreased action potential amplitude of the extensor digitorum brevis muscle, and (e) motor weakness of muscles within the anterior compartment. Generally, higher intracompartment at pressures caused more rapid deterioration of neuromuscular function. In two subjects, when in situ compression levels were 0 and 30 mm Hg, normal neuromuscular function was maintained for 3 h. Threshold pressures for significant dysfunction were not always the same for each functional parameter studied, and the magnitudes of each functional deficit did not always correlate with compression level. This variable tolerance to elevated pressure emphasizes the need to monitor clinical signs and symptoms carefully in the diagnosis of compartment syndromes. The nature of the present studies was short term; longer term compression of myoneural tissues may result in dysfunction at lower pressure thresholds.

Dietary fat oxidation as a function of body fat.

PubMed

Westerterp, Klaas R; Smeets, Astrid; Lejeune, Manuela P; Wouters-Adriaens, Mirjam P E; Westerterp-Plantenga, Margriet S

2008-01-01

It is hypothesized that low dietary fat oxidation makes subjects prone to weight gain. The aim of the study was to determine dietary fat oxidation in normal, overweight, and obese subjects. The subjects were 38 women and 18 men with a mean (+/-SD) age of 30+/-12 y and a body mass index (in kg/m2) of 25+/-4 (range: 18-39). Dietary fat oxidation was measured with deuterated palmitic acid, given simultaneously with breakfast, while the subjects were fed under controlled conditions in a respiration chamber. Body composition was measured by hydrodensitometry and deuterium dilution. Dietary fat oxidation, measured over 12 h after breakfast, ranged from 4% to 28% with a mean (+/-SD) of 16+/-6%. Dietary fat oxidation was negatively related to percentage body fat, and lean subjects had the highest and obese subjects the lowest values (r=-0.65, P<0.001). The observed reduction in dietary fat oxidation in subjects with a higher percentage body fat may play a role in human obesity.

[A comparative study on family perception between abused children and normal children by Kinetic Family Drawing].

PubMed

Lee, Haeng Ja; Kim, Young Hae; Park, Nam Hee

2006-04-01

The study attempted to find family perception differences between abused children and normal children by Kinetic Family Drawing. The subjects of the study consisted of two groups, 143 abused who were in the upper 25th percentile, and 150 normal who were in the lower 25th percentile. Collected Kinetic Family Drawings were divided into five dimensions such as actions, human figure characteristics, dynamics, styles and symbols, and they was analyzed with SPSS/WIN 10.0. In the perception about their family in action dimension, their family in figure characteristics dimension, their family in dynamics dimensions, and their family in symbols dimension, there is a sharp contrast between the two groups. Putting these results together, abused children feel lower self-esteem and feel more sense of alienation in their family than normal children do. In addition, abused children perceive their parents as negative and aggressive people.

Preserved circadian rhythm of serum insulin concentration at low plasma glucose during fasting in lean and overweight humans.

PubMed

Merl, Volker; Peters, Achim; Oltmanns, Kerstin M; Kern, Werner; Hubold, Christian; Hallschmid, Manfred; Born, Jan; Fehm, Horst L; Schultes, Bernd

2004-11-01

Circadian rhythms in glucose metabolism are well documented. Most studies, however, evaluated such variations under conditions of continuous glucose supply, either via food intake or glucose infusion. Here we assessed in 30 subjects circadian variations in concentrations of plasma glucose, serum insulin, and C-peptide during a 72-hour fasting period to evaluate rhythms independent from glucose supply. Furthermore we assessed differences in these parameters between normal-weight (n = 20) and overweight (n = 10) subjects. Blood was sampled every 4 hours. During fasting, plasma glucose, serum insulin, and C-peptide levels gradually decreased (all P < .001). While there was no circadian variation in plasma glucose levels after the first day of fasting, serum levels of insulin were constantly higher in the morning (8.00 h) than at night (0.00 h) (P < .001), although the extent of this morning-associated rise in insulin levels decreased with the time spent fasting (P = .001). Also, morning C-peptide concentrations were higher compared to the preceding night (P < .001). The C-peptide/insulin ratio (CIR) decreased during prolonged fasting (P = .030), suggesting a decrease in hepatic insulin clearance. Moreover, CIR was significantly lower in the morning than at the night of day 1 and day 2 of fasting (P = .010 and P = .004, respectively). Compared to normal-weight subjects, overweight subjects had higher plasma glucose, as well as serum insulin and C-peptide levels (all P < .03). Data indicate preserved circadian rhythms in insulin concentrations in the presence of substantially decreased glucose levels in normal-weight and overweight subjects. This finding suggests a central nervous system contribution to the regulation of insulin secretion independent of plasma glucose levels.

Evaluation of nasal IgA secretion in normal subjects by nasal spray and aspiration.

PubMed

Fujimoto, Chisa; Kido, Hiroshi; Sawabuchi, Takako; Mizuno, Dai; Hayama, Masaki; Yanagawa, Hiroaki; Takeda, Noriaki

2009-06-01

Nasal washing (NW) is a popular method for collecting human nasal lavage fluid. However, for NW the subject must be trained, and the method is unsuitable for field studies on untrained subjects. To overcome this problem, we have developed an easy and painless method, a nasal spray and aspiration (NSA) method. This method is different from NW in that the nasal cavity is misted over with saline, and the nasal lavage fluid is aspirated from the nostrils through a silicon tube. First, nasal lavage fluid was obtained twice by NSA with an interval of a week between lavages to evaluate intraindividual variability, and the IgA and protein levels in the nasal lavage fluid were measured by enzyme-linked immunosorbent assay and bicinchoninic acid assay, respectively. Next, the IgA value determined by NSA was compared with that by NW in another 12 normal subjects 2 days after NSA. In 10 normal subjects, mean volume of saline sprayed into the nose was 0.46+/-0.15 ml (mean+/-S.D.). Mean volume of aspirated nasal lavage fluid containing both sprayed saline and nasal secretion was 0.44+/-0.37 ml. The mean IgA level/mg protein in the nasal lavage fluid determined by NSA was 112+/-18 microg/mg protein at the first and 99+/-20 at the second times of measurement, being highly reproducible. The mean value by NSA was 114+/-19 microg/mg protein, being almost the same as that by NW of 99+/-27. These findings suggest that the IgA level/mg protein in nasal lavage fluid determined by NSA instead of NW might be useful for assessing the variability of nasal IgA secretion.

Gut Microbiota and Metabolic Endotoxemia in Young Obese Mexican Subjects

PubMed Central

Radilla-Vázquez, Romina Belén; Parra-Rojas, Isela; Martínez-Hernández, Norma Edith; Márquez-Sandoval, Yolanda Fabiola; Illades-Aguiar, Berenice; Castro-Alarcón, Natividad

2016-01-01

Background The gut microbiota plays an important role in human metabolism; previous studies suggest that the imbalance can cause a metabolic endotoxemia that may be linked to weight gain and insulin resistance. The purpose of this study was to investigate the relationship between the gut microbiota composition, the lipopolysaccharide levels and the metabolic profile in obese and normal-weight young subjects. Methods We studied 32 obese (BMI ≥ 30 kg/m2) and 32 normal-weight subjects (BMI = 18.5-24.9 kg/m2), aged 18-25 years. Quantification of intestinal bacteria was performed by real-time PCR. Endotoxin units were determined with the test QCL-1000, and biochemical profile was performed under a standard protocol of Spinreact. Results Obese individuals had a BMI of 34.5 (32.9-36.45) kg/m2, increased triglycerides (123 vs. 70 mg/dl), total cholesterol (168 vs. 142 mg/dl), and LDL-cholesterol (114 vs. 96.5 mg/dl). In obese subjects body temperature was higher than in normal-weight subjects. We found a greater number of Clostridum leptum and Lactobacillus (p < 0.001) and lower numbers of Prevotella and Escherichia coli (p < 0.001) in the obese group. A decrease of E. coli was associated with an increased risk of lipopolysaccharide levels ranging from 1 to 1.3 EU/ml. A positive correlation was found between serum lipopolysaccharides and BMI (r = 0.46, p = 0.008), triglyceride levels (r = 0.44, p = 0.011) as well as waist circumference (r = 0.34, p = 0.040), being more evident in young obese females. Conclusion Subclinical metabolic endotoxemia determined by serum concentration of lipopolysaccharides was related to the smallest amount of E. coli, high triglyceride levels, and central adiposity in obese young persons. PMID:26745497

Acute effects of clonidine and growth-hormone-releasing hormone on growth hormone secretion in patients with hyperthyroidism.

PubMed

Giustina, A; Buffoli, M G; Bussi, A R; Wehrenberg, W B

1991-01-01

Patients with hyperthyroidism have reduced growth hormone (GH) responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of clonidine on GH secretion has been suggested to depend on an enhancement of hypothalamic GH-releasing hormone (GHRH) release. The aim of our study was to evaluate the effects of clonidine and GHRH on GH secretion in patients with hyperthyroidism. Eight hyperthyroid females with recent diagnosis of Graves' disease (age range 20-55 years, body mass index range 19.2-26.2 kg/m2) and 6 healthy female volunteers (age range 22-35 years, body mass index range 19-25 kg/m2) underwent two experimental trials at no less than 7-day intervals: (a) an intravenous infusion of clonidine 150 micrograms in 10 ml of saline, or (b) a bolus intravenous injection of human GHRH (1-29)NH2, 100 micrograms in 1 ml of saline. Hyperthyroid patients showed blunted GH peaks after clonidine (7.1 +/- 1.7 micrograms/l) as compared to normal subjects receiving clonidine (28.5 +/- 4.9 micrograms/l, p less than 0.05). GH peaks after GHRH were also significantly lower in hyperthyroid subjects (8.0 +/- 1.7 micrograms/l) as compared to normal subjects receiving GHRH (27.5 +/- 4.4 micrograms/l, p less than 0.05). No significant differences in the GH values either after clonidine or GHRH were observed in the two groups of subjects examined. Our data demonstrate that the GH responses to clonidine as well as to GHRH in patients with hyperthyroidism are inhibited in a similar fashion with respect to normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomography arthrography with traction in the human hip for three-dimensional reconstruction of cartilage and the acetabular labrum

PubMed Central

Henak, C.R.; Abraham, C.L.; Peters, C.L.; Sanders, R.K.; Weiss, J.A.; Anderson, A.E.

2014-01-01

AIM To develop and demonstrate the efficacy of a computed tomography arthrography (CTA) protocol for the hip that enables accurate three-dimensional reconstructions of cartilage and excellent visualization of the acetabular labrum. MATERIALS AND METHODS Ninety-three subjects were imaged (104 scans); 68 subjects with abnormal anatomy, 11 patients after periacetabular osteotomy surgery, and 25 subjects with normal anatomy. Fifteen to 25 ml of contrast agent diluted with lidocaine was injected using a lateral oblique approach. A Hare traction splint applied traction during CT. The association between traction force and intra-articular joint space was assessed qualitatively under fluoroscopy. Cartilage geometry was reconstructed from the CTA images for 30 subjects; the maximum joint space under traction was measured. RESULTS Using the Hare traction splint, the intra-articular space and boundaries of cartilage could be clearly delineated throughout the joint; the acetabular labrum was also visible. Dysplastic hips required less traction (~5 kg) than normal and retroverted hips required (>10 kg) to separate the cartilage. An increase in traction force produced a corresponding widening of the intra-articular joint space. Under traction, the maximum width of the intra-articular joint space during CT ranged from 0.98–6.7 mm (2.46 ± 1.16 mm). CONCLUSIONS When applied to subjects with normal and abnormal hip anatomy, the CTA protocol presented yields clear delineation of the cartilage and the acetabular labrum. Use of a Hare traction splint provides a simple, cost-effective method to widen the intra-articular joint space during CT, and provides flexibility to vary the traction as required. PMID:25070373

Right hemispheric dominance in gaze-triggered reflexive shift of attention in humans.

PubMed

Okada, Takashi; Sato, Wataru; Toichi, Motomi

2006-11-01

Recent findings suggest a right hemispheric dominance in gaze-triggered shifts of attention. The aim of this study was to clarify the dominant hemisphere in the gaze processing that mediates attentional shift. A target localization task, with preceding non-predicative gaze cues presented to each visual field, was undertaken by 44 healthy subjects, measuring reaction time (RT). A face identification task was also given to determine hemispheric dominance in face processing for each subject. RT differences between valid and invalid cues were larger when presented in the left rather than the right visual field. This held true regardless of individual hemispheric dominance in face processing. Together, these results indicate right hemispheric dominance in gaze-triggered reflexive shifts of attention in normal healthy subjects.

A passive exoskeleton with artificial tendons: design and experimental evaluation.

PubMed

van Dijk, Wietse; van der Kooij, Herman; Hekman, Edsko

2011-01-01

We developed a passive exoskeleton that was designed to minimize joint work during walking. The exoskeleton makes use of passive structures, called artificial tendons, acting in parallel with the leg. Artificial tendons are elastic elements that are able to store and redistribute energy over the human leg joints. The elastic characteristics of the tendons have been optimized to minimize the mechanical work of the human leg joints. In simulation the maximal reduction was 40 percent. The performance of the exoskeleton was evaluated in an experiment in which nine subjects participated. Energy expenditure and muscle activation were measured during three conditions: Normal walking, walking with the exoskeleton without artificial tendons, and walking with the exoskeleton with the artificial tendons. Normal walking was the most energy efficient. While walking with the exoskeleton, the artificial tendons only resulted in a negligibly small decrease in energy expenditure. © 2011 IEEE

Detection of human papilloma virus 16 and 18 DNA sequences by southern blot hybridization in oral leukoplakia and squamous cell carcinoma.

PubMed

Khanna, Rahul; Rao, G R K; Tiwary, S K; Rai, Ashish; Khanna, Seema; Khanna, A K

2009-04-01

The etiopathological role of human papilloma virus (HPV) in the causation of oral cancer is till a subject of speculation. We used the technique of Southern blot hybridization to detect the presence of HPV types 16 & 18 in biopsy specimens from oral cancer and leukoplakia patients as well as normal oral mucosal biopsies. The prevalence of either HPV type 16 or 18 was found in 64.5% (29/45) of oral cancer, 40%(12/30) of leukoplakia and 20%(9/45) of normal oral mucosal biopsies. No association could be demonstrated between tobacco usage habits or a history of genital warts with HPV prevalence. A significant finding was that none of the oral cancer patients were negative for both: a history of tobacco usage as well as presence of HPV infection, on Southern blot hybridization.

Fluid-dynamics modelling of the human left ventricle with dynamic mesh for normal and myocardial infarction: preliminary study.

PubMed

Khalafvand, S S; Ng, E Y K; Zhong, L; Hung, T K

2012-08-01

Pulsating blood flow patterns in the left ventricular (LV) were computed for three normal subjects and three patients after myocardial infarction (MI). Cardiac magnetic resonance (MR) images were obtained, segmented and transformed into 25 frames of LV for a computational fluid dynamics (CFD) study. Multi-block structure meshes were generated for 25 frames and 75 intermediate grids. The complete LV cycle was modelled by using ANSYS-CFX 12. The flow patterns and pressure drops in the LV chamber of this study provided some useful information on intra-LV flow patterns with heart diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nonpathologizing trauma interventions in abnormal psychology courses.

PubMed

Hoover, Stephanie M; Luchner, Andrew F; Pickett, Rachel F

2016-01-01

Because abnormal psychology courses presuppose a focus on pathological human functioning, nonpathologizing interventions within these classes are particularly powerful and can reach survivors, bystanders, and perpetrators. Interventions are needed to improve the social response to trauma on college campuses. By applying psychodynamic and feminist multicultural theory, instructors can deliver nonpathologizing interventions about trauma and trauma response within these classes. We recommend class-based interventions with the following aims: (a) intentionally using nonpathologizing language, (b) normalizing trauma responses, (c) subjectively defining trauma, (d) challenging secondary victimization, and (e) questioning the delineation of abnormal and normal. The recommendations promote implications for instructor self-reflection, therapy interventions, and future research.

Sensation seeking as a common factor in opioid dependent subjects and high risk sport practicing subjects. A cross sectional study.

PubMed

Franques, P; Auriacombe, M; Piquemal, E; Verger, M; Brisseau-Gimenez, S; Grabot, D; Tignol, J

2003-03-01

Animal research has outlined a vulnerability trait to drug dependence like behavior. The behavioral characteristic of this vulnerability is hyperactivity in response to a novel environment of which sensation seeking (SS) has been suggested as a possible equivalent in humans. If this is the case, SS should be more frequent in drug dependent and risky sports practicing subjects then controls. The objective of this study was to determine if opioid dependent subjects (ODS) and regular paragliders (RP) would be more SS then normal controls. Cross sectional study. Three groups of 34 individuals (total 102) matched for age and sex were selected from ODS seeking treatment, a paragliding club, and a college staff. Global and sub-scores of the Zuckerman sensation seeking scale (SSS). Non parametric statistics (Kruskal Wallis and Wilcoxon 2-Sample Tests) were used given the non-normal distribution of SSS scores in the ODS and RP groups. Significant differences were found across the three groups for the Thrill and Adventure Seeking (TAS) (P = 0.001), dishinibition (Dis) (P = 0.0003) and total score (P = 0.001). ODS and RP scored significantly higher than controls on two (Dis and the TAS scales). RP also scored significantly higher on the Boredom Susceptibility (BS) scale (P = 0.04). Our results show that RP and ODS differ from controls and have some similarities based on the SSS. In this study, the ODS and the RP could express different forms of a general tendency to seek intense and abrupt sensations through various behaviors. Our results in humans are in favor of the hypothesis that the behavioral trait of vulnerability to drug dependence behavior is expressed through SS. Copyright 2002 Elsevier Science Ireland Ltd.

Self-oscillating Vocal Fold Model Mechanics: Healthy, Diseased, and Aging

NASA Astrophysics Data System (ADS)

Hiubler, Elizabeth P.; Pollok, Lucas F. E.; Apostoli, Adam G.; Hancock, Adrienne B.; Plesniak, Michael W.

2014-11-01

Voice disorders have been estimated to have a substantial economic impact of 2.5 billion annually. Approximately 30% of people will suffer from a voice disorder at some point in their lives. Life-sized, self-oscillating, synthetic vocal fold (VF) models are fabricated to exhibit material properties representative of human VFs. These models are created both with and without a polyp-like structure, a pathology that has been shown to produce rich viscous flow structures not normally observed for healthy VFs during normal phonation. Pressure measurements are acquired upstream of the VFs and high-speed images are captured at varying flow rates during VF oscillation to facilitate an understanding of the characteristics of healthy and diseased VFs. The images are analyzed using a videokymography line-scan technique. Clinically-relevant parameters calculated from the volume-velocity output of a circumferentially-vented mask (Rothenberg mask) are compared to human data collected from two groups of males aged 18-30 and 60-80. This study extends the use of synthetic VF models by assessing their ability to replicate behaviors observed in human subject data to advance a means of investigating changes associated with normal, pathological, and the aging voice. Supported by the GWU Institute for Biomedical Engineering (GWIBE) and GWU Center for Biomimetics and Bioinspired Engineering (COBRE).

Creatinine and HMH (5-hydroxy-1-methylhydantoin, NZ-419) as intrinsic hydroxyl radical scavengers.

PubMed

Ienaga, K; Yokozawa, T

2011-08-01

Creatinine (Crn) is one of the main intrinsic hydroxyl radical (•OH) scavengers and an ideal one for healthy or normal mammals, although this fact has not yet become widely accepted. Our results from urinary data estimated that ca. 0.4-0.6% of Crn is used daily to scavenge •OH in normal mammals [ca. 50 μmole and ca. 400 pmole of •OH in healthy subjects and normal rats, respectively]. In human subjects, Crn reacts non-enzymatically with •OH to form creatol (CTL: 5-hydroxycreatinine) and demethylcreatinine (DMC) in a one to one ratio, and CTL partially decomposes to methylguanidine (MG). And so, the scavenged mole of •OH by Crn is nearly equal to their molar total sum (CTL + MG + DMC) or 2 × (CTL + MG). The molar ratio of (scavenged •OH)/Crn in healthy subjects and normal rats are 4.4 and 6.0 mmole/mole, respectively, i.e. almost similar, but in patients with chronic kidney disease (CKD) the ratio increases up to ca. 60 mmole/mole in proportion to the severity of CKD. Since the level of Crn might not be enough to scavenge all •OH, and MG starts accumulating as a uremic toxin, Crn is not really the ideal scavenger. 5-Hydroxy-1-methylhydantoin (HMH, NZ-419), a Crn metabolite, is another antioxidant, having •OH scavenging ability, and has been shown to inhibit the progression of CKD in rats in stead of Crn, if sufficient amounts are given orally.

Impact of body fat percentage change on future diabetes in subjects with normal glucose tolerance.

PubMed

Zhao, Tianxue; Lin, Ziwei; Zhu, Hui; Wang, Chen; Jia, Weiping

2017-12-01

The aim of the work was to determine the effect of body fat change on risk of diabetes in normal glucose tolerance (NGT) population. A total of 1,857 NGT subjects were included and followed up for an average period of 44.57 months. Body fat percentage (BF%) was measured by bioelectrical impedance analysis. Subjects were grouped based on the BF% and/or body mass index (BMI) state. Among all subjects, 28 developed diabetes after follow-up. Compared with subjects with stable normal BF% (control), subjects who became obesity at follow-up were defects in insulin secretion and had a higher risk of developing diabetes (7.102, 95% confidence intervals [CI] 1.740-28.993), while no difference in diabetic risk could be viewed between subjects with abnormal BF% at baseline but normal at the end of follow-up and control subjects after adjustment of confounding factors. Moreover, compared with those keeping normal BF% and BMI both at baseline and follow-up, subjects who had normal BMI at baseline and follow-up, but abnormal BF% at baseline or/and follow-up still had a higher risk to develop diabetes (4.790, 95% CI 1.061-21.621), while those with normal BF% at baseline and follow-up, but abnormal BMI at baseline or/and follow-up had not. Subjects from normal BF% at baseline to obese at follow-up are associated with an increased risk of diabetes. Maintaining normal body fat is more relevant than BMI in preventing diabetes. © 2017 IUBMB Life, 69(12):947-955, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Loadcell supports for a dynamic force plate. [using piezoelectric tranducers and electromyography to study human gait

NASA Technical Reports Server (NTRS)

Keller, C. W.; Musil, L. M.; Hagy, J. L.

1975-01-01

An apparatus was developed to accurately measure components of force along three mutually perpendicular axes, torque, and the center of pressure imposed by the foot of a subject walking over its surface. The data obtained were used to supplement high-speed motion picture and electromyographic (EMG) data for in-depth studies of normal or abnormal human gait. Significant features of the design (in particular, the mechanisms used to support the loadcell transducers) are described. Results of the development program and typical data obtained with the device are presented and discussed.

Skin strain patterns provide kinaesthetic information to the human central nervous system.

PubMed Central

Edin, B B; Johansson, N

1995-01-01

1. We investigated the contribution of skin strain-related sensory inputs to movement perception and execution in five normal volunteers. The dorsal and palmar skin of the middle phalanx and the proximal interphalangeal (PIP) joint were manipulated to generate specific strain patterns in the proximal part of the index finger. To mask sensations directly related to this manipulation, skin and deeper tissues were blocked distal to the mid-portion of the proximal phalanx of the index finger by local anaesthesia. 2. Subjects were asked to move their normal right index finger either to mimic any perceived movements of the anaesthetized finger or to touch the tip of the insentient finger. 3. All subjects readily reproduced actual movements induced by the experimenter at the anaesthetized PIP joint. However, all subjects also generated flexion movements when the experimenter did not induce actual movement but produced deformations in the sentient proximal skin that were similar to those observed during actual PIP joint flexion. Likewise, the subjects indicated extension movement at the PIP joint when strain patterns corresponding to extension movements were induced. 4. In contrast, when the skin strain in the proximal part of the index finger was damped by a ring applied just proximal to the PIP joint within the anaesthetized skin area, both tested subjects failed to perceive PIP movements that actually took place.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 Figure 3 PMID:7473253

Transport and metabolism of sarcosine in hypersarcosinemic and normal phenotypes

PubMed Central

Glorieux, Francis H.; Scriver, Charles R.; Delvin, Edgard; Mohyuddin, Fazl

1971-01-01

An adolescent male proband with hypersarcosinemia was discovered incidentally in a French-Canadian family; no specific disease was associated with the trait. The hypersarcosinemia is not diminished by dietary folic acid even in pharmacologic doses (30 mg/day). The normal absence of sarcosine dehydrogenase in cultured human skin fibroblasts and in leukocytes was confirmed, thus eliminating these tissues as useful sources for further investigation of mutant sarcosinemic phenotypes and genotypes. The response in plasma of sarcosine and glycine, after sarcosine loading, distinguished the normal subject from the subjects who were presumably homozygous and heterozygous for the hypersarcosinemia allele. Sarcosine clearance from plasma was delayed greatly (t½, 6.1 hr) in the presumed homozygote and slightly (t½, 2.2 hr) in the presumed heterozygote, while plasma glycine remained constant in the former and rose in the latter. Normal subjects clear sarcosine from plasma rapidly (t½, 1.6 hr) while their plasma glycine trend is downward. The phenotypic responses suggest that hypersarcosinemia is an autosomal recessive trait in this pedigree. Renal tubular transport of sarcosine was normal in the proband even though he presumably lacked the sarcosine oxidation which should normally occur in kidney. Sarcosine catabolism is thus not important for its own renal uptake. Sarcosine interacts with proline and glycine during its absorption in vivo. Studies in vitro in rat kidney showed that sarcosine transport is mediated, saturable, and energy dependent. Sarcosine has no apparent transport system of its own; it uses the low Km transport systems for L-proline and glycine to a minor extent and a high Km system shared by these substances for the major uptake at concentrations encountered in hypersarcosinemia. Intracellular sarcosine at high concentration will exchange with glycine on one of these systems, which may explain a paradoxical improvement in renal transport of glycine after sarcosine loading in the hypersarcosinemic proband. PMID:5096515

Vessel Sampling and Blood Flow Velocity Distribution With Vessel Diameter for Characterizing the Human Bulbar Conjunctival Microvasculature.

PubMed

Wang, Liang; Yuan, Jin; Jiang, Hong; Yan, Wentao; Cintrón-Colón, Hector R; Perez, Victor L; DeBuc, Delia C; Feuer, William J; Wang, Jianhua

2016-03-01

This study determined (1) how many vessels (i.e., the vessel sampling) are needed to reliably characterize the bulbar conjunctival microvasculature and (2) if characteristic information can be obtained from the distribution histogram of the blood flow velocity and vessel diameter. Functional slitlamp biomicroscope was used to image hundreds of venules per subject. The bulbar conjunctiva in five healthy human subjects was imaged on six different locations in the temporal bulbar conjunctiva. The histograms of the diameter and velocity were plotted to examine whether the distribution was normal. Standard errors were calculated from the standard deviation and vessel sample size. The ratio of the standard error of the mean over the population mean was used to determine the sample size cutoff. The velocity was plotted as a function of the vessel diameter to display the distribution of the diameter and velocity. The results showed that the sampling size was approximately 15 vessels, which generated a standard error equivalent to 15% of the population mean from the total vessel population. The distributions of the diameter and velocity were not only unimodal, but also somewhat positively skewed and not normal. The blood flow velocity was related to the vessel diameter (r=0.23, P<0.05). This was the first study to determine the sampling size of the vessels and the distribution histogram of the blood flow velocity and vessel diameter, which may lead to a better understanding of the human microvascular system of the bulbar conjunctiva.

Androgen receptor is overexpressed in boys with severe hypospadias, and ZEB1 regulates androgen receptor expression in human foreskin cells

PubMed Central

Qiao, Liang; Tasian, Gregory E.; Zhang, Haiyang; Cao, Mei; Ferretti, Max; Cunha, Gerald R.; Baskin, Laurence S.

2012-01-01

INTRODUCTION ZEB1 is overexpressed in patients with severe hypospadias. We examined the interaction between ZeB1 and the androgen receptor (AR) in vitro and the expression of AR in boys with hypospadias. RESULTS ZEB1 and AR colocalize to the nucleus. Estrogen upregulated ZEB1 and AR expression. Chromatin immunoprecipitation (ChIP) demonstrated that ZEB1 binds to an E-box sequence in the AR gene promoter. AR expression is higher in subjects with severe hypospadias than those with mild hypospadias and control subjects (P < 0.05). ZEB1 physically interacts with AR in human foreskin cells. DISCUSSION AR is overexpressed in patients with severe hypospadias. Environmental estrogenic compounds may increase the risk of hypospadias by facilitating the interaction between ZEB1 and AR. METHODS Hs68 cells, a fibroblast cell line derived from neonatal human foreskin, were exposed to 0, 10, and 100 nmol/l of estrogen, after which the cellular localization of ZEB1 and AR was assessed using immunocytochemistry. To determine if ZEB1 interacted with the AR gene, ChIP was performed using ZEB1 antibody and polymerase chain reaction (PCR) for AR. Second, AR expression was quantified using real-time PcR and western blot in normal subjects (n = 32), and subjects with mild (n = 16) and severe hypospadia (n = 16). PMID:22391641

Urea inhibits NaK2Cl cotransport in human erythrocytes.

PubMed Central

Lim, J; Gasson, C; Kaji, D M

1995-01-01

We examined the effect of urea on NaK2Cl cotransport in human erythrocytes. In erythrocytes from nine normal subjects, the addition of 45 mM urea, a concentration commonly encountered in uremic subjects, inhibited NaK2Cl cotransport by 33 +/- 7%. Urea inhibited NaK2Cl cotransport reversibly, and in a concentration-dependent fashion with half-maximal inhibition at 63 +/- 10 mM. Acute cell shrinkage increased, and acute cell swelling decreased NaK2Cl cotransport in human erythrocytes. Okadaic acid (OA), a specific inhibitor of protein phosphatase 1 and 2A, increased NaK2Cl cotransport by nearly 80%, suggesting an important role for these phosphatases in the regulation of NaK2Cl cotransport. Urea inhibited bumetanide-sensitive K influx even when protein phosphatases were inhibited with OA, suggesting that urea acted by inhibiting a kinase. In cells subjected to shrinking and OA pretreatment, maneuvers expected to increase the net phosphorylation, urea inhibited cotransport only minimally, suggesting that urea acted by causing a net dephosphorylation of the cotransport protein, or some key regulatory protein. The finding that concentrations of urea found in uremic subjects inhibited NaK2Cl cotransport, a widespread transport pathway with important physiological functions, suggests that urea is not only a marker for accumulation of other uremic toxins, but may be a significant uremic toxin itself. PMID:7593597

The epidermal growth factor receptor (EGF-R) is present on the basolateral, but not the apical, surface of enterocytes in the human gastrointestinal tract.

PubMed Central

Playford, R J; Hanby, A M; Gschmeissner, S; Peiffer, L P; Wright, N A; McGarrity, T

1996-01-01

BACKGROUND: While it is clear that luminal epidermal growth factor (EGF) stimulates repair of the damaged bowel, its significance in maintaining normal gut growth remains uncertain. If EGF is important in maintaining normal gut growth, the EGF receptor (EGF-R) should be present on the apical (luminal) surface in addition to the basolateral surface. AIMS/SUBJECTS/METHODS: This study examined the distribution of the EGF-R in the epithelium throughout the human gastro-intestinal tract using immunohistochemistry, electron microscopy, and western blotting of brush border preparations. RESULTS: Immunostaining of the oesophagus showed circumferential EGF-R positivity in the cells of the basal portions of the stratified squamous epithelium but surface cells were EGF-R negative. In the normal stomach, small intestine, and colon, immunostaining localised the receptor to the basolateral surface with the apical membranes being consistently negative. EGF-R positivity within the small intestine appeared to be almost entirely restricted to the proliferative (crypt) region. Western blotting demonstrated a 170 kDa protein in whole tissue homogenates but not in the brush border vesicle preparations. CONCLUSIONS: As the EGF-R is located only on the basolateral surfaces in the normal adult gastrointestinal tract, the major role of luminal EGF is probably to stimulate repair rather than to maintain normal gut growth. Images Figure 1 Figure 2 Figure 3 PMID:8977341

Psychological effects of MDE in normal subjects. Are entactogens a new class of psychoactive agents?

PubMed

Hermle, L; Spitzer, M; Borchardt, D; Kovar, K A; Gouzoulis, E

1993-02-01

The so-called entactogens 3,4-methylenedioxymethamphetamine ([MDMA] also known as "Ecstasy," or "Adam") and its analog 3,4-methylenedioxyethamphetamine ([MDE] also known as "Eve") exert similar psychotropic effects in humans. Two double-blind placebo-controlled psychometric studies with normal control subjects were conducted. Placebo or MDE (140 mg) was administered orally to eight male volunteers at 1:30 P.M. and to six subjects (3 male, 3 female) at 11 P.M. Psychologic tests and clinical ratings were performed 1 hour before the administration of the drugs, as well as 2, 5, and 24 hours after drug intake and 7 days thereafter in the first study. In the second study, measures were taken at times -1, +8.5, +24 hours, and +7 days. The majority of the psychotropic effects resembled those that have already been described in anecdotal reports. The substance produced a partially controllable state of enhanced insight, empathy, and peaceful feelings. All subjects displayed a general stimulation with increased psychomotor drive, logorrhea, and facilitation of communication. One of the fourteen volunteers developed a toxic psychosis. One volunteer displayed a dysphoric reaction, one suffered from episodes of anxiety for some days after the experiment. The findings support the hypothesis that MDMA and MDE represent a novel pharmacologic class.

Eye Dominance Predicts fMRI Signals in Human Retinotopic Cortex

PubMed Central

Mendola, Janine D.; Conner, Ian P.

2009-01-01

There have been many attempts to define eye dominance in normal subjects, but limited consensus exists, and relevant physiological data is scarce. In this study, we consider two different behavioral methods for assignment of eye dominance, and how well they predict fMRI signals evoked by monocular stimulation. Sighting eye dominance was assessed with two standard tests, the Porta Test, and a ‘hole in hand’ variation of the Miles Test. Acuity dominance was tested with a standard eye chart and with a computerized test of grating acuity. We found limited agreement between the sighting and acuity methods for assigning dominance in our individual subjects. We then compared the fMRI response generated by dominant eye stimulation to that generated by non-dominant eye, according to both methods, in 7 normal subjects. The stimulus consisted of a high contrast hemifield stimulus alternating with no stimulus in a blocked paradigm. In separate scans, we used standard techniques to label the borders of visual areas V1, V2, V3, VP, V4, V3A, and MT. These regions of interest (ROIs) were used to analyze each visual area separately. We found that percent change in fMRI BOLD signal was stronger for the dominant eye as defined by the acuity method, and this effect was significant for areas located in the ventral occipital territory (V1v, V2v, VP, V4). In contrast, assigning dominance based on sighting produced no significant interocular BOLD differences. We conclude that interocular BOLD differences in normal subjects exist, and may be predicted by acuity measures. PMID:17194544

Insulin resistance is associated with diminished endoplasmic reticulum stress responses in adipose tissue of healthy and diabetic subjects.

PubMed

Boden, Guenther; Cheung, Peter; Kresge, Karen; Homko, Carol; Powers, Ben; Ferrer, Lucas

2014-09-01

We recently showed that insulin increased ER stress in human adipose tissue. The effect of insulin resistance on ER stress is not known. It could be decreased, unchanged, or increased, depending on whether insulin regulates ER stress via the metabolic/phosphoinositide 3-kinase (PI3K) or alternate signaling pathways. To address this question, we examined effects of lipid-induced insulin resistance on insulin stimulation of ER stress. mRNAs of several ER stress markers were determined in fat biopsies obtained before and after 8-h hyperglycemic-hyperinsulinemic clamping in 13 normal subjects and in 6 chronically insulin-resistant patients with type 2 diabetes mellitus (T2DM). In normal subjects, hyperglycemia-hyperinsulinemia increased after/before mRNA ratios of several ER stress markers (determined by ER stress pathway array and by individual RT-PCR). Lipid infusion was associated with inhibition of the PI3K insulin-signaling pathway and with a decrease of hyperinsulinemia-induced ER stress responses. In chronically insulin-resistant patients with T2DM, hyperglycemic-hyperinsulinemia did not increase ER stress response marker mRNAs. In summary, insulin resistance, either produced by lipid infusions in normal subjects or chronically present in T2DM patients, was associated with decreased hyperinsulinemia-induced ER stress responses. This suggests, but does not prove, that these two phenomena were causally related. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

A computer analysis of reflex eyelid motion in normal subjects and in facial neuropathy.

PubMed

Somia, N N; Rash, G S; Epstein, E E; Wachowiak, M; Sundine, M J; Stremel, R W; Barker, J H; Gossman, D

2000-12-01

To demonstrate how computerized eyelid motion analysis can quantify the human reflex blink. Seventeen normal subjects and 10 patients with unilateral facial nerve paralysis were analyzed. Eyelid closure is currently evaluated by systems primarily designed to assess lower/midfacial movements. The methods are subjective, difficult to reproduce, and measure only volitional closure. Reflex closure is responsible for eye hydration, and its evaluation demands dynamic analysis. A 60Hz video camera incorporated into a helmet was used to analyze blinking. Reflective markers on the forehead and eyelids allowed for the dynamic measurement of the reflex blink. Eyelid displacement, velocity and acceleration were calculated. The degree of synchrony between bilateral blinks was also determined. This study demonstrates that video motion analysis can describe normal and altered eyelid motions in a quantifiable manner. To our knowledge, this is the first study to measure dynamic reflex blinks. Eyelid closure may now be evaluated in kinematic terms. This technique could increase understanding of eyelid motion and permit more accurate evaluation of eyelid function. Dynamic eyelid evaluation has immediate applications in the treatment of facial palsy affecting the reflex blink. Relevance No method has been developed that objectively quantifies dynamic eyelid closure. Methods currently in use evaluate only volitional eyelid closure, and are based on direct and indirect observer assessments. These methods are subjective and are incapable of analyzing dynamic eyelid movements, which are critical to maintenance of corneal hydration and comfort. A system that quantifies eyelid kinematics can provide a functional analysis of blink disorders and an objective evaluation of their treatment(s).

A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults123

PubMed Central

Stote, Kim S; Baer, David J; Spears, Karen; Paul, David R; Harris, G Keith; Rumpler, William V; Strycula, Pilar; Najjar, Samer S; Ferrucci, Luigi; Ingram, Donald K; Longo, Dan L; Mattson, Mark P

2009-01-01

Background Although consumption of 3 meals/d is the most common pattern of eating in industrialized countries, a scientific rationale for this meal frequency with respect to optimal health is lacking. A diet with less meal frequency can improve the health and extend the lifespan of laboratory animals, but its effect on humans has never been tested. Objective A pilot study was conducted to establish the effects of a reduced-meal-frequency diet on health indicators in healthy, normal-weight adults. Design The study was a randomized crossover design with two 8-wk treatment periods. During the treatment periods, subjects consumed all of the calories needed for weight maintenance in either 3 meals/d or 1 meal/d. Results Subjects who completed the study maintained their body weight within 2 kg of their initial weight throughout the 6-mo period. There were no significant effects of meal frequency on heart rate, body temperature, or most of the blood variables measured. However, when consuming 1 meal/d, subjects had a significant increase in hunger; a significant modification of body composition, including reductions in fat mass; significant increases in blood pressure and in total, LDL-, and HDL-cholesterol concentrations; and a significant decrease in concentrations of cortisol. Conclusions Normal-weight subjects are able to comply with a 1 meal/d diet. When meal frequency is decreased without a reduction in overall calorie intake, modest changes occur in body composition, some cardiovascular disease risk factors, and hematologic variables. Diurnal variations may affect outcomes. PMID:17413096

Altered inflammation, paraoxonase-1 activity and HDL physicochemical properties in obese humans with and without Prader-Willi syndrome

PubMed Central

Ferretti, Gianna; Bacchetti, Tiziana; Masciangelo, Simona; Grugni, Graziano; Bicchiega, Virginia

2012-01-01

SUMMARY Prader-Willi syndrome (PWS) represents the most common form of genetic obesity. Several studies confirm that obesity is associated with inflammation, oxidative stress and impairment of antioxidant systems; however, no data are available concerning PWS subjects. We compared levels of plasma lipids and C-reactive protein (CRP) in 30 subjects of ‘normal’ weight (18.5–25 kg/m2), 15 PWS obese (>30 kg/m2) subjects and 13 body mass index (BMI)-matched obese subjects not affected by PWS. In all subjects, we evaluated the levels of lipid hydroperoxides and the activity of paraoxonase-1 (PON1), an enzyme involved in the antioxidant and anti-inflammatory properties exerted by high-density lipoproteins (HDLs). Furthermore, using the fluorescent molecule of Laurdan, we investigated the physicochemical properties of HDLs isolated from normal weight and obese individuals. Altogether, our results demonstrated, for the first time, higher levels of lipid hydroperoxides and a lower PON1 activity in plasma of obese individuals with PWS with respect to normal-weight controls. These alterations are related to CRP levels, with a lower PON1:CRP ratio in PWS compared with non-PWS obese subjects. The study of Laurdan fluorescence parameters showed significant modifications of physicochemical properties in HDLs from PWS individuals. Whatever the cause of obesity, the increase of adiposity is associated with inflammation, oxidative stress and alterations in HDL compositional and functional properties. PMID:22822045

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage.

PubMed

Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

2016-07-01

Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele.

ELECTROMAGNETIC PHENOMENA WHICH RADIATE FROM THE HUMAN BRAIN DURING INTENSE PSYCHOSENSORIAL ACTIVITY FROM DREAMY, HALLUCINATORY AND TELEPSYCHIC STATES,

DTIC Science & Technology

intense psychosensorial activity (oneirism, hallucinations, telepsychism). Oneirism is the peculiar psychic condition that is favorable to dreams ...normal hallucinatory phenomena during the sleep and dream -like stages of the beginning sleep and of the reverie. As hallucinations, are designated as the...whole gamut of subjective metapsychics (cryptesthesia, spontaneous or pragmatic; lucidity: clairvoyance: telepathy ; rhabdomancy; radiesthesia; graphonomy; cartomancy; chiromancy). (Author)

A Comparison of National Policies on Research Involving Human Subjects to Facilitate Review and Approval of Collaborative Research

DTIC Science & Technology

2008-11-26

Exemptions: 1. Routine educational testing 2. Quality assurance studies 3. Strict performance reviews 4. Occupational training 5. Anonymous data...following categories are exempt from this policy: (1) Research conducted in established or commonly accepted educational settings, involving normal... educational practices, such as (i) research on regular and special education instructional strategies, or (ii) research on the effectiveness of or the

Cardiovascular studies in the rhesus monkey. [brain circulation during stress

NASA Technical Reports Server (NTRS)

Stone, H. L.; Sandler, H.

1977-01-01

Criteria are given for selecting the macaca mulatta as the analogue of the human in the study of cerebral circulation, particularly the control of the cerebral vascular bed during normal and stressful conditions. Topics discussed include surgical preparation of subject; responses to changes in arterial pressure, oxygen, and carbon dioxide; innervation of cerebral vessels; cerebral flow response to acceleration; and cerebral blood flow and cerebellar stimulation.

Dietary strawberries increase proliferative response of CD3/CD28-activated CD8+ T cells and production of TNF-alpha in lipopolysaccharide-stimulated monocytes from obese human subjects

USDA-ARS?s Scientific Manuscript database

Obesity increases the risk of developing bacterial and viral infections compared to normal weight. In a 7 wk double-blind, randomized, crossover trial, twenty obese volunteers (20-50 y old, BMI between 30-40 kg/m2) were fed freeze-dried strawberry powder or strawberry-flavored placebo preparations ...

Biomedical Effects of Chemical-Threat-Agent Antidote and Pretreatment Drugs. An Abstracted Bibliography. Volume 1.

DTIC Science & Technology

1986-04-01

Adams, R., Venna, P., Jackson, A., and Miller, R. TITLE: Plasma pharmacokinetics of intravenously administered atropine in normal human subjects Journal...atropine by i.v. route and inhalation. Measurements of respiratory airway resistance, N2 closing volume, maximal expiratory flow volume, pressure volume...maximum flow -static recoil and esophageal elasticity were compared to non-atropinized values. FINDINGS: "I.V. administration produced a marked

Human Response to Pyridostigmine Bromide.

DTIC Science & Technology

1984-03-01

Lack of adverse effects other than overdose symptoms, it can be concluded that administration of pyridostigmine to normal subject is prob- abLy safe...neuromuscular transmission. Based on the results of the military studies and the general lack M of side effects other than overdose symptoms cited in the...Bentz, E.W., and StoeLting, R.K., Prolonged Response to Succiny l choline Fol lowing Pancuronium Reversal with Pyridostigmine, Anesthesiology 44, 258

Dietary grape powder increases IL-1ß and IL-6 production by lipopolysaccharide-activated monocytes and reduces plasma concentrations of large LDL-cholesterol particles in obese humans

USDA-ARS?s Scientific Manuscript database

Obesity increases the risk of developing cardiovascular disease, hypertension, type 2 diabetes, and bacterial and viral infections when compared to the normal weight population. In a 9 wk randomised, double-blind crossover study, 24 obese subjects between 20-60 y old and with a BMI between 30-45 k...

Within-step modulation of leg muscle activity by afferent feedback in human walking

PubMed Central

Klint, Richard af; Nielsen, Jens Bo; Cole, Jonathan; Sinkjaer, Thomas; Grey, Michael J

2008-01-01

To maintain smooth and efficient gait the motor system must adjust for changes in the ground on a step-to-step basis. In the present study we investigated the role of sensory feedback as 19 able-bodied human subjects walked over a platform that mimicked an uneven supporting surface. Triceps surae muscle activation was assessed during stance as the platform was set to different inclinations (±3 deg, ±2 deg and 0 deg rotation in a parasagittal plane about the ankle). Normalized triceps surae muscle activity was significantly increased when the platform was inclined (2 deg: 0.153 ± 0.051; 3 deg: 0.156 ± 0.053) and significantly decreased when the platform was declined (−3 deg: 0.133 ± 0.048; −2 deg: 0.132 ± 0.049) compared with level walking (0.141 ± 0.048) for the able-bodied subjects. A similar experiment was performed with a subject who lacked proprioception and touch sensation from the neck down. In contrast with healthy subjects, no muscle activation changes were observed in the deafferented subject. Our results demonstrate that the ability to compensate for small irregularities in the ground surface relies on automatic within-step sensory feedback regulation rather than conscious predictive control. PMID:18669536

Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor

NASA Technical Reports Server (NTRS)

Brainard, G. C.; Hanifin, J. P.; Greeson, J. M.; Byrne, B.; Glickman, G.; Gerner, E.; Rollag, M. D.

2001-01-01

The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 +/- 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects' pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 0.91), which identifies 446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.

EEG mapping and low-resolution brain electromagnetic tomography (LORETA) in diagnosis and therapy of psychiatric disorders: evidence for a key-lock principle.

PubMed

Saletu, Bernd; Anderer, Peter; Saletu-Zyhlarz, Gerda M; Pascual-Marqui, Roberto D

2005-04-01

Different psychiatric disorders, such as schizophrenia with predominantly positive and negative symptomatology, major depression, generalized anxiety disorder, agoraphobia, obsessive-compulsive disorder, multi-infarct dementia, senile dementia of the Alzheimer type and alcohol dependence, show EEG maps that differ statistically both from each other and from normal controls. Representative drugs of the main psychopharmacological classes, such as sedative and non-sedative neuroleptics and antidepressants, tranquilizers, hypnotics, psychostimulants and cognition-enhancing drugs, induce significant and typical changes to normal human brain function, which in many variables are opposite to the above-mentioned differences between psychiatric patients and normal controls. Thus, by considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. This is supported by 3-dimensional low-resolution brain electromagnetic tomography (LORETA), which identifies regions within the brain that are affected by psychiatric disorders and psychopharmacological substances.

Psychiatric symptomatology and the recall of positive and negative personality information.

PubMed

Furnham, A; Cheng, H

1996-09-01

Various studies from the cognitive information processing tradition have shown that neuroticism is particularly associated with the preferential processing of negative information about the self. Just over 60 'normal' subjects completed the Langner (1962, Journal of Health and Human Behaviour, 3, 269-276) 22 measure of minor psychiatric symptoms. Later, they were presented with a list of positive, neutral and negative trait words for self-rating. After 1 hr, subjects were asked to recall all the trait words. As predicted, the Langner (1962) score was associated with an increased probability of recalling negative self-referent information (r = 0.36). Implications for therapy are considered.

Do enteric neurons make hypocretin?

PubMed

Baumann, Christian R; Clark, Erika L; Pedersen, Nigel P; Hecht, Jonathan L; Scammell, Thomas E

2008-04-10

Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, sectioned tissue, pre-treatment of mice with colchicine, and the use of various primary antisera), we could not identify hypocretin-producing cells in enteric nervous tissue collected from mice or normal human subjects. These results raise doubts about whether enteric neurons produce hypocretin.

Evidence for a possible role of oxygen free radicals in the abnormal functional arterial vasomotion in insulin dependent diabetes.

PubMed

Ceriello, A; Quatraro, A; Caretta, F; Varano, R; Giugliano, D

1990-01-01

A functional arterial spasm, revealed by reduced post-ischemic response, is present in diabetic subjects with no overt evidence of vascular damage. The administration of three different antioxidant agents, vitamin C, thiopronine and glutathione, produces an increase of basal blood flow in both diabetic and normal subjects, and ameliorates significantly the vascular functional response in diabetes. These data suggest that free radicals may play a role in the regulation of arterial resistance in humans, and that a de-regulation of their action may be involved in the development of arterial dysfunction in diabetes.

Transient elastographic evaluation in adult subjects without overt liver disease: influence of alanine aminotransferase levels.

PubMed

Kumar, Manoj; Sharma, Praveen; Garg, Hitendra; Kumar, Ramesh; Bhatia, Vikram; Sarin, Shiv K

2011-08-01

  Studies on normal values of liver stiffness (LS) in subjects at "low risk" for liver disease are scant. The aim of the present study was to assess liver stiffness values in the subjects without overt liver disease with normal alanine aminotransferases (ALT) and to determine potential factors, which may influence these values with special reference to newly suggested updated upper limits of normal for ALT.   Liver stiffness measurements were performed in 445 subjects without overt liver disease (mean age, 41.1±13.6; male, 73.5%) and normal liver enzymes.   Mean LS value was 5.10±1.19kPa. LS values were higher in men than in women (5.18±1.67 vs 4.86±1.24kPa, respectively, P=0.008); in subjects with higher body mass index (BMI) category (Normal, overweight and obese subjects; 4.10±0.75, 5.08±0.66, and 6.05±1.28kPa, respectively; P<0.001); in subjects with metabolic syndrome than in those without (5.63±1.37 vs 5.01±1.14kPa, P=0.001); and in subjects with ALT levels more than updated limits of normal compared to subjects with ALT levels less than updated limits of normal (5.68±1.21 vs 4.77±1.05kPa, P<0.001). On multiple linear regression, BMI and ALT was found to be significant predictor of LS.   Liver stiffness values in subjects without overt liver disease with normal ALT are influenced by BMI and ALT levels. Subjects with ALT levels less than updated limits of normal have lower LS values as compared to those with higher levels. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Non-nutritive sweeteners: no class effect on the glycemic or appetite responses to ingested glucose

PubMed Central

Bryant, Charlotte E.; Wasse, Lucy K.; Astbury, Nerys; Nandra, Gurinder; McLaughlin, John T.

2014-01-01

There is considerable interest in whether non-nutritive sweeteners are sensed in the gastrointestinal tract to modulate appetitive or absorptive responses to ingested carbohydrate. We determined the effect of a panel of non-nutritive sweeteners, aspartame, saccharin and acesulfame-K, delivered in doses that would be consumed in normal usage. Each was given in combination with glucose, assessing their effect on glycemic responses and appetite in ten healthy human subjects. There was no additional effect of aspartame or saccharin on the blood glucose response to oral glucose at any time point, although acesulfame-K exerted a small effect. However, none had an effect on perceptions of hunger or fullness. We conclude that there is no consistent evidence that non-nutrient sweeteners, when acutely consumed with glucose in dietetically relevant doses, have a class effect in modulating blood glucose in healthy human subjects. However, acesulfame-K may require further exploration. PMID:24595225

Inflammation and immune system activation in aging: a mathematical approach.

PubMed

Nikas, Jason B

2013-11-19

Memory and learning declines are consequences of normal aging. Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects. By employing a rigorous, multi-method bioinformatic approach, I identified 36 genes that were the most significant in terms of differential expression; and by employing mathematical modeling, I demonstrated that 7 of the 36 genes were able to discriminate between the old and young subjects with high accuracy. Remarkably, 90% of the known genes from those 36 most significant genes are associated with either inflammation or immune system activation. This suggests that chronic inflammation and immune system over-activity may underlie the aging process of the human brain, and that potential anti-inflammatory treatments targeting those genes may slow down this process and alleviate its symptoms.

Studies in porphyria: functional evidence for a partial deficiency of ferrochelatase activity in mitogen-stimulated lymphocytes from patients with erythropoietic protoporphyria.

PubMed Central

Sassa, S; Zalar, G L; Poh-Fitzpatrick, M B; Anderson, K E; Kappas, A

1982-01-01

In this paper we show that the ferrochelatase defect in erythropoietic protoporphyria (EPP) can readily be identified in mitogen-stimulated lymphocytes since such cells from patients with EPP accumulate approximately twice as much protoporphyrin IX as cells from normal subjects when incubated with a porphyrin precursor, gamma-aminolevulinic acid (ALA). Treatment of cultures with ALA and with the iron chelator, CaMgEDTA significantly increased the level of protoporphyrin IX in mitogen-stimulated lymphocytes from normal subjects, while the same treatment failed to produce an increase in protoporphyrin IX in cell preparations from EPP patients. In contrast to the results with the chelator treatment, supplementation of the cultures with iron and ALA reduced the level of protoporphyrin IX in normal cells, but not in EPP cells. These findings are compatible with a partial deficiency of ferrochelatase in EPP lymphocytes. The gene defects of acute intermittent porphyria and hereditary coproporphyria have previously been identified using lymphocyte preparations from the gene carriers of these diseases. The present study demonstrates that EPP represents another form of human porphyria in which the gene defect of the disease can now be identified in lymphocyte preparations. PMID:6804493

Midkine and pleiotrophin concentrations in needle biopsies of breast and lung masses.

PubMed

Giamanco, Nicole M; Jee, Youn Hee; Wellstein, Anton; Shriver, Craig D; Summers, Thomas A; Baron, Jeffrey

2017-09-07

Midkine (MDK) and pleiotrophin (PTN) are two closely related heparin-binding growth factors which are overexpressed in a wide variety of human cancers. We hypothesized that the concentrations of these factors in washout of biopsy needles would be higher in breast and lung cancer than in benign lesions. Seventy subjects underwent pre-operative core needle biopsies of 78 breast masses (16 malignancies). In 11 subjects, fine needle aspiration was performed ex vivo on 7 non-small cell lung cancers and 11 normal lung specimens within surgically excised lung tissue. The biopsy needle was washed with buffer for immunoassay. The MDK/DNA and the PTN/DNA ratio in most of the malignant breast masses were similar to the ratios in benign masses except one lobular carcinoma in situ (24-fold higher PTN/DNA ratio than the average benign mass). The MDK/DNA and PTN/DNA ratio were similar in most malignant and normal lung tissue except one squamous cell carcinoma (38-fold higher MDK/DNA ratio than the average of normal lung tissue). Both MDK and PTN are readily measurable in washout of needle biopsy samples from breast and lung masses and levels are highly elevated only in a specific subset of these malignancies.

Detection of erythropoietin misuse by the Athlete Biological Passport combined with reticulocyte percentage.

PubMed

Bejder, Jacob; Aachmann-Andersen, Niels Jacob; Bonne, Thomas Christian; Olsen, Niels Vidiendal; Nordsborg, Nikolai Baastrup

2016-10-01

The sensitivity of the adaptive model of the Athlete Biological Passport (ABP) and reticulocyte percentage (ret%) in detection of recombinant human erythropoietin (rHuEPO) misuse was evaluated using both a long-term normal dose and a brief high dose treatment regime. Sixteen subjects received either 65 IU rHuEPO × kg -1 every second day for two weeks (normal-dose), 390 IU rHuEPO × kg -1 on three consecutive days (high-dose), or frequent placebo treatment for 13 days in a randomized, placebo-controlled, double-blind crossover design. Blood variables were measured 4, 11, and 25 days following treatment initiation. The ABP based on haemoglobin concentration ([Hb]) and OFF-hr score ([Hb] - 60 × √ret%) yielded atypical profiles following both normal-dose and high-dose treatment (0 %, 31 %, 13 % vs. 21 %, 33 %, 20 % at days 4, 11, and 25 after normal and high dose, respectively). Including ret% as a stand-alone marker for atypical blood profiles increased (P < 0.05) the sensitivity of the adaptive model at day 11 to 63 % and 67 % for normal-dose and high-dose rHuEPO administration, respectively. In conclusion, ~30 % of subjects injecting a normal-dose rHuEPO for two weeks or a high-dose rHuEPO for three days will present an atypical ABP profile. Including ret% as a stand-alone parameter improves the sensitivity two-fold. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

The efficacy of vitamin C supplementation on reducing total serum cholesterol in human subjects: a review and analysis of 51 experimental trials

PubMed Central

McRae, Marc P.

2006-01-01

Abstract Objective Observational studies in humans have shown an inverse relationship between plasma vitamin C concentration and total serum cholesterol. However, experimental studies have shown inconsistent results regarding the ability of vitamin C to reduce total serum cholesterol. Methods Published reports of trials studying the effects of vitamin C on serum lipids were identified by a search of Medline from 1966 to 2004. Data from 51 experimental studies comprising of 1666 pooled subjects were selected for analysis. Results A very strong negative association was observed between baseline total serum cholesterol and the percent change in cholesterol (r = −0.585, p<0.001). When subjects were divided into 4 groups based on their baseline total serum cholesterol levels, the following weighted mean percent changes in cholesterol from baseline were observed: normal cholesterol (<199mg/dl): 0.91±6.8% (n=508); borderline high cholesterol (200–239mg/dl): 3.90±5.78% (n=605); high cholesterol (240–279mg/dl): 11.40±7.96% (n=300); severe cholesterol (>280mg/dl): 14.30±8.36% (n=253). A significant inverse relationship was found between the baseline plasma vitamin C concentrations and mean percent change in total cholesterol from baseline (r = −0.500, p<0.005). It was also observed that the high and severe baseline cholesterol groups possessed lower baseline plasma vitamin C concentrations than those in the normal cholesterol groups (0.79 and 0.55 versus 1.24 mg/dl respectively). Conclusion This finding strengthens the hypothesis that the cholesterol lowering and cardio-protective benefit of vitamin C supplementation may be in its ability to elevate plasma vitamin C concentrations in those patients who initially possess lower than normal vitamin C plasma concentrations. PMID:19674666

CCDC65 Mutation Causes Primary Ciliary Dyskinesia with Normal Ultrastructure and Hyperkinetic Cilia

PubMed Central

Horani, Amjad; Brody, Steven L.; Ferkol, Thomas W.; Shoseyov, David; Wasserman, Mollie G.; Ta-shma, Asaf; Wilson, Kate S.; Bayly, Philip V.; Amirav, Israel; Cohen-Cymberknoh, Malena; Dutcher, Susan K.; Elpeleg, Orly; Kerem, Eitan

2013-01-01

Background Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by impaired ciliary function, leading to chronic sinopulmonary disease. The genetic causes of PCD are still evolving, while the diagnosis is often dependent on finding a ciliary ultrastructural abnormality and immotile cilia. Here we report a novel gene associated with PCD but without ciliary ultrastructural abnormalities evident by transmission electron microscopy, but with dyskinetic cilia beating. Methods Genetic linkage analysis was performed in a family with a PCD subject. Gene expression was studied in Chlamydomonas reinhardtii and human airway epithelial cells, using RNA assays and immunostaining. The phenotypic effects of candidate gene mutations were determined in primary culture human tracheobronchial epithelial cells transduced with gene targeted shRNA sequences. Video-microscopy was used to evaluate cilia motion. Results A single novel mutation in CCDC65, which created a termination codon at position 293, was identified in a subject with typical clinical features of PCD. CCDC65, an orthologue of the Chlamydomonas nexin-dynein regulatory complex protein DRC2, was localized to the cilia of normal nasal epithelial cells but was absent in those from the proband. CCDC65 expression was up-regulated during ciliogenesis in cultured airway epithelial cells, as was DRC2 in C. reinhardtii following deflagellation. Nasal epithelial cells from the affected individual and CCDC65-specific shRNA transduced normal airway epithelial cells had stiff and dyskinetic cilia beating patterns compared to control cells. Moreover, Gas8, a nexin-dynein regulatory complex component previously identified to associate with CCDC65, was absent in airway cells from the PCD subject and CCDC65-silenced cells. Conclusion Mutation in CCDC65, a nexin-dynein regulatory complex member, resulted in a frameshift mutation and PCD. The affected individual had altered cilia beating patterns, and no detectable ultrastructural defects of the ciliary axoneme, emphasizing the role of the nexin-dynein regulatory complex and the limitations of certain methods for PCD diagnosis. PMID:23991085

Lipid-free apolipoprotein A-I and discoidal reconstituted high-density lipoproteins differentially inhibit glucose-induced oxidative stress in human macrophages.

PubMed

Tabet, Fatiha; Lambert, Gilles; Cuesta Torres, Luisa F; Hou, Liming; Sotirchos, Irene; Touyz, Rhian M; Jenkins, Alicia J; Barter, Philip J; Rye, Kerry-Anne

2011-05-01

The goal of this study was to investigate the mechanisms by which apolipoprotein (apo) A-I, in the lipid-free form or as a constituent of discoidal reconstituted high-density lipoproteins ([A-I]rHDL), inhibits high-glucose-induced redox signaling in human monocyte-derived macrophages (HMDM). HMDM were incubated under normal (5.8 mmol/L) or high-glucose (25 mmol/L) conditions with native high-density lipoproteins (HDL) lipid-free apoA-I from normal subjects and from subjects with type 2 diabetes (T2D) or (A-I)rHDL. Superoxide (O2-) production was measured using dihydroethidium fluorescence. NADPH oxidase activity was assessed using lucigenin-derived chemiluminescence and a cyotochrome c assay. p47phox translocation to the plasma membrane, Nox2, superoxide dismutase 1 (SOD1), and SOD2 mRNA and protein levels were determined by real-time polymerase chain reaction and Western blotting. Native HDL induced a time-dependent inhibition of O2- generation in HMDM incubated with 25 mmol/L glucose. Lipid-free apoA-I and (A-I)rHDL increased SOD1 and SOD2 levels and attenuated 25 mmol/L glucose-mediated increases in cellular O2-, NADPH oxidase activity, p47 translocation, and Nox2 expression. Lipid-free apoA-I mediated its effects on Nox2, SOD1, and SOD2 via ABCA1. (A-I)rHDL-mediated effects were via ABCG1 and scavenger receptor BI. Lipid-free apoA-I from subjects with T2D inhibited reactive oxygen species generation less efficiently than normal apoA-I. Native HDL, lipid-free apoA-I and (A-I)rHDL inhibit high-glucose-induced redox signaling in HMDM. The antioxidant properties of apoA-I are attenuated in T2D.

Stationary Apparatus Would Apply Forces of Walking to Feet

NASA Technical Reports Server (NTRS)

Hauss, Jessica; Wood, John; Budinoff, Jason; Correia, Michael; Albrecht, Rudolf

2006-01-01

A proposed apparatus would apply controlled cyclic forces to both feet for the purpose of preventing the loss of bone density in a human subject whose bones are not subjected daily to the mechanical loads of normal activity in normal Earth gravitation. The apparatus was conceived for use by astronauts on long missions in outer space; it could also be used by bedridden patients on Earth, including patients too weak to generate the necessary forces by their own efforts. The apparatus (see figure) would be a modified version of a bicycle-like exercise machine, called the cycle ergometer with vibration isolation system (CEVIS), now aboard the International Space Station. Attached to each CEVIS pedal would be a computer-controlled stress/ vibration exciter connected to the heel portion of a special-purpose pedal. The user would wear custom shoes that would amount to standard bicycle shoes equipped with cleats for secure attachment of the balls of the feet to the special- purpose pedals. If possible, prior to use of the apparatus, the human subject would wear a portable network of recording accelerometers, while walking, jogging, and running. The information thus gathered would be fed to the computer, wherein it would be used to make the exciters apply forces and vibrations closely approximating the forces and vibrations experienced by that individual during normal exercise. It is anticipated that like the forces applied to bones during natural exercise, these artificial forces would stimulate the production of osteoblasts (bone-forming cells), as needed to prevent or retard loss of bone mass. In addition to helping to prevent deterioration of bones, the apparatus could be used in treating a person already suffering from osteoporosis. For this purpose, the magnitude of the applied forces could be reduced, if necessary, to a level at which weak hip and leg bones would still be stimulated to produce osteoblasts without exposing them to the full stresses of walking and thereby risking fracture.

Ultrasonic propulsion of kidney stones: preliminary results of human feasibility study.

PubMed

Bailey, Michael; Cunitz, Bryan; Dunmire, Barbrina; Paun, Marla; Lee, Franklin; Ross, Susan; Lingeman, James; Coburn, Michael; Wessells, Hunter; Sorensen, Mathew; Harper, Jonathan

2014-09-03

One in 11 Americans has experienced kidney stones, with a 50% average recurrence rate within 5-10 years. Ultrasonic propulsion (UP) offers a potential method to expel small stones or residual fragments before they become a recurrent problem. Reported here are preliminary findings from the first investigational use of UP in humans. The device uses a Verasonics ultrasound engine and Philips HDI C5-2 probe to generate real-time B-mode imaging and targeted "push" pulses on demand. There are three arms of the study: de novo stones, post-lithotripsy fragments, and the preoperative setting. A pain questionnaire is completed prior to and following the study. Movement is classified based on extent. Patients are followed for 90 days. Ten subjects have been treated to date: three de novo , five post-lithotripsy, and two preoperative. None of the subjects reported pain associated with the treatment or a treatment related adverse event, beyond the normal discomfort of passing a stone. At least one stone was moved in all subjects. Three of five post-lithotripsy subjects passed a single or multiple stones within 1-2 weeks following treatment; one subject passed two (1-2 mm) fragments before leaving clinic. In the pre-operative studies we successfully moved 7 - 8 mm stones. In four subjects, UP revealed multiple stone fragments where the clinical image and initial ultrasound examination indicated a single large stone.

Abdominal Fat and Sarcopenia in Women Significantly Alter Osteoblasts Homeostasis In Vitro by a WNT/β-Catenin Dependent Mechanism

PubMed Central

Wannenes, Francesca; Papa, Vincenza; Greco, Emanuela A.; Fornari, Rachele; Marocco, Chiara; Di Luigi, Luigi; Donini, Lorenzo M.; Lenzi, Andrea

2014-01-01

Obesity and sarcopenia have been associated with mineral metabolism derangement and low bone mineral density (BMD). We investigated whether imbalance of serum factors in obese or obese sarcopenic patients could affect bone cell activity in vitro. To evaluate and characterize potential cellular and molecular changes of human osteoblasts, cells were exposed to sera of four groups of patients: (1) affected by obesity with normal BMD (O), (2) affected by obesity with low BMD (OO), (3) affected by obesity and sarcopenia (OS), and (4) affected by obesity, sarcopenia, and low BMD (OOS) as compared to subjects with normal body weight and normal BMD (CTL). Patients were previously investigated and characterized for body composition, biochemical and bone turnover markers. Then, sera of different groups of patients were used to incubate human osteoblasts and evaluate potential alterations in cell homeostasis. Exposure to OO, OS, and OOS sera significantly reduced alkaline phosphatase, osteopontin, and BMP4 expression compared to cells exposed to O and CTL, indicating a detrimental effect on osteoblast differentiation. Interestingly, sera of all groups of patients induced intracellular alteration in Wnt/β-catenin molecular pathway, as demonstrated by the significant alteration of specific target genes expression and by altered β-catenin cellular compartmentalization and GSK3β phosphorylation. In conclusion our results show for the first time that sera of obese subjects with low bone mineral density and sarcopenia significantly alter osteoblasts homeostasis in vitro, indicating potential detrimental effects of trunk fat on bone formation and skeletal homeostasis. PMID:24963291

Seropositivity for the human heat shock protein (Hsp)60 accompanying seropositivity for Chlamydia trachomatis is less prevalent among tubal ectopic pregnancy cases than individuals with normal reproductive history.

PubMed

Ozyurek, Eser S; Karacan, Tolga; Ozdalgicoglu, Cenk; Yilmaz, Salih; Isik, Salman; San, Mevlide; Kaya, Erdal

2018-04-01

To investigate the role of anti-human heat shock protein 60 (hHsp60) antibody positivity in the pathogenesis of ectopic pregnancy, following Chlamydia trachomatis (CT) infection. In a case-control study, serological tests for anti-hHsp60 were performed in ectopic pregnancies (study group) and parturients with normal reproductive histories (control group). All participants in both groups were CT IgG(+). hHsp60 IgG(+) prevalences were compared between the two groups, by semiquantitative ELISA. Data were evaluated using nonparametric and parametric tests and multivariable regression. After an initial pilot study, two groups were formed: 63 ectopic gestations (study group) and 95 normal parturients (control group), all CT IgG(+). Blood samples from all cases were tested for anti-hHsp60 IgG. Age, gravidity, and practising contraception were higher in the control group, while a history of pelvic infections were more common in the study group. Hsp60 IgG(+) was found to be significantly higher in the control group (63/95, 66.3%) compared to study group (30/63, 47.6%). Regression analysis revealed anti-hHsp60 positivity was an independent factor delineating the two groups. Immunity to hHsp60 is less common in CT IgG(+) ectopic pregnancies than CT IgG(+) fertile subjects without a history of ectopic pregnancies. Hence, our findings suggest that hHsp60 seropositivity may decrease the probability of an ectopic gestation in subjects with previous CT infections. Copyright © 2018 Elsevier B.V. All rights reserved.

Impaired spontaneous anthropomorphizing despite intact perception and social knowledge

PubMed Central

Heberlein, Andrea S.; Adolphs, Ralph

2004-01-01

Humans spontaneously imbue the world with social meaning: we see not only emotions and intentional behaviors in humans and other animals, but also anger in the movements of thunderstorms and willful sabotage in crashing computers. Converging evidence supports a role for the amygdala, a collection of nuclei in the temporal lobe, in processing emotionally and socially relevant information. Here, we report that a patient with bilateral amygdala damage described a film of animated shapes (normally seen as full of social content) in entirely asocial, geometric terms, despite otherwise normal visual perception. Control tasks showed that the impairment did not result from a global inability to describe social stimuli or a bias in language use, nor was a similar impairment observed in eight comparison subjects with damage to orbitofrontal cortex. This finding extends the role of the amygdala to the social attributions we make even to stimuli that are not explicitly social and, in so doing, suggests that the human capacity for anthropomorphizing draws on some of the same neural systems as do basic emotional responses. PMID:15123799

Rotational movement (circling) in normal humans: sex difference and relationship to hand, foot and eye preference.

PubMed

Bracha, H S; Seitz, D J; Otemaa, J; Glick, S D

1987-05-19

An endogenous asymmetry in striatal dopaminergic function has been identified in rats, and related to spontaneous and drug-induced circling (rotation, turning). We have developed an electronic device for measuring in humans the same kinds of rotational movements observed in rats. Our data indicate that, without being aware of the type of information being obtained, normal men and women rotate preferentially to the left or to the right during a routine day. Women had higher average rates of rotation than men. Males that were consistently right-sided (left-hemisphere dominant) for hand, foot and eye dominance rotated more to the right than to the left, whereas left-hemisphere dominant females rotated more to the left than to the right. Subjects tested on two occasions, 6 weeks apart, exhibited consistent (significantly correlated) rotational preferences--this was much more evident in left-hemisphere dominant than in mixed dominance individuals. In view of similar animal data, the device used in this study may become a useful and objective means for obtaining quantitative information regarding the status of basal ganglia function in humans.

Profiling CpG island field methylation in both morphologically normal and neoplastic human colonic mucosa.

PubMed

Belshaw, N J; Elliott, G O; Foxall, R J; Dainty, J R; Pal, N; Coupe, A; Garg, D; Bradburn, D M; Mathers, J C; Johnson, I T

2008-07-08

Aberrant CpG island (CGI) methylation occurs early in colorectal neoplasia. Quantitative methylation-specific PCR profiling applied to biopsies was used to quantify low levels of CGI methylation of 18 genes in the morphologically normal colonic mucosa of neoplasia-free subjects, adenomatous polyp patients, cancer patients and their tumours. Multivariate statistical analyses distinguished tumour from mucosa with a sensitivity of 78.9% and a specificity of 100% (P=3 x 10(-7)). In morphologically normal mucosa, age-dependent CGI methylation was observed for APC, AXIN2, DKK1, HPP1, N33, p16, SFRP1, SFRP2 and SFRP4 genes, and significant differences in CGI methylation levels were detected between groups. Multinomial logistic regression models based on the CGI methylation profiles from normal mucosa correctly identified 78.9% of cancer patients and 87.9% of non-cancer (neoplasia-free+polyp) patients (P=4.93 x 10(-7)) using APC, HPP1, p16, SFRP4, WIF1 and ESR1 methylation as the most informative variables. Similarly, CGI methylation of SFRP4, SFRP5 and WIF1 correctly identified 61.5% of polyp patients and 78.9% of neoplasia-free subjects (P=0.0167). The apparently normal mucosal field of patients presenting with neoplasia has evidently undergone significant epigenetic modification. Methylation of the genes selected by the models may play a role in the earliest stages of the development of colorectal neoplasia.

Sensory Feedback in Interlimb Coordination: Contralateral Afferent Contribution to the Short-Latency Crossed Response during Human Walking.

PubMed

Gervasio, Sabata; Voigt, Michael; Kersting, Uwe G; Farina, Dario; Sinkjær, Thomas; Mrachacz-Kersting, Natalie

2017-01-01

A constant coordination between the left and right leg is required to maintain stability during human locomotion, especially in a variable environment. The neural mechanisms underlying this interlimb coordination are not yet known. In animals, interneurons located within the spinal cord allow direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with the legs moving in opposite directions). An inverse dynamics model was applied to estimate the gastrocnemius muscle proprioceptors' firing rate. During normal walking, a significant correlation was observed between the magnitude of SLCRs and the estimated muscle spindle secondary afferent activity (P = 0.04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary afferents, likely plays a significant role in generating the SLCR. This observation has important implications for our understanding of what future research should be focusing on to optimize locomotor recovery in patient populations.

Neural connectivity of the posterior body of the fornix in the human brain: diffusion tensor imaging study.

PubMed

Jang, Sung Ho; Kwon, Hyeok Gyu

2013-08-09

Little is known about the neural connectivity of the fornix in the human brain. In the current study, using diffusion tensor imaging, we attempted to investigate the neural connectivity of the posterior body of the fornix in the normal human brain. A total of 43 healthy subjects were recruited for this study. DTIs were acquired using a sensitivity-encoding head coil at 1.5T. For connectivity of the posterior body of the fornix, a seed region of interest was used on the posterior body of the fornix. Connectivity was defined as the incidence of connection between the posterior body of the fornix and any neural structure of the brain at the threshold of 5, 25, and 50 streamline. At the threshold of 5, 25, and 50, the posterior body of the fornix showed connectivity to the precentral gyrus (37%, 19%, and 15%), the postcentral gyrus (25%, 11.5%, and 7%), the posterior parietal cortex (16.5%, 5%, and 5%), the brainstem (12%, 4.5%, and 3.5%), the crus of the fornix (34%, 10.5%, and 7%), the contralateral splenium of the corpus callosum (12.5%, 5%, and 0%), and the ipsilateral splenium of the CC (69.8%%, 33.7%, and 23.3%), respectively. Findings of this study showed that the posterior body of the fornix had connectivity with the cerebral cortex, the brainstem, the fornical crus, and the contralateral splenium through the splenium of the corpus callosum in normal subjects. We believe that the results of this study would be helpful in investigation of the neural network related to memory and recovery mechanisms following fornical injury in the human brain. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Human lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy

PubMed Central

Modi, S; Stanton, A W B; Svensson, W E; Peters, A M; Mortimer, P S; Levick, J R

2007-01-01

Axillary surgery for breast cancer partially obstructs lymph outflow from the arm, chronically raising the lymphatic smooth muscle afterload. This may lead to pump failure, as in hypertensive cardiac failure, and could explain features of breast cancer treatment-related lymphoedema (BCRL) such as its delayed onset. A new method was developed to measure human lymphatic contractility non-invasively and test the hypothesis of contractile impairment. 99mTc-human IgG (Tc-HIG), injected into the hand dermis, drained into the arm lymphatic system which was imaged using a gamma-camera. Lymph transit time from hand to axilla, ttransit, was 9.6 ± 7.2 min (mean ±s.d.) (velocity 8.9 cm min−1) in seven normal subjects. To assess lymphatic contractility, a sphygmomanometer cuff around the upper arm was inflated to 60 mmHg (Pcuff) before 99mTc-HIG injection and maintained for >> ttransit. When Pcuff exceeded the maximum pressure generated by the lymphatic pump (Ppump), radiolabelled lymph was held up at the distal cuff border. Pcuff was then lowered in 10 mmHg steps until 99mTc-HIG began to flow under the cuff to the axilla, indicating Ppump≥Pcuff. In 16 normal subjects Ppump was 39 ± 14 mmHg. Ppump was 38% lower in 16 women with BCRL, namely 24 ± 19 mmHg (P = 0.014, Student's unpaired t test), and correlated negatively with the degree of swelling (12–56%). Blood radiolabel accumulation proved an unreliable measure of lymphatic pump function. Lymphatic congestion lymphoscintigraphy thus provided a quantitative measure of human lymphatic contractility without surgical cut-down, and the results supported the hypothesis of lymphatic pump failure in BCRL. PMID:17569739

Sensor Spatial Distortion, Visual Latency, and Update Rate Effects on 3D Tracking in Virtual Environments

NASA Technical Reports Server (NTRS)

Ellis, S. R.; Adelstein, B. D.; Baumeler, S.; Jense, G. J.; Jacoby, R. H.; Trejo, Leonard (Technical Monitor)

1998-01-01

Several common defects that we have sought to minimize in immersing virtual environments are: static sensor spatial distortion, visual latency, and low update rates. Human performance within our environments during large amplitude 3D tracking was assessed by objective and subjective methods in the presence and absence of these defects. Results show that 1) removal of our relatively small spatial sensor distortion had minor effects on the tracking activity, 2) an Adapted Cooper-Harper controllability scale proved the most sensitive subjective indicator of the degradation of dynamic fidelity caused by increasing latency and decreasing frame rates, and 3) performance, as measured by normalized RMS tracking error or subjective impressions, was more markedly influenced by changing visual latency than by update rate.

Calcium orthophosphates: occurrence, properties, biomineralization, pathological calcification and biomimetic applications.

PubMed

Dorozhkin, Sergey V

2011-01-01

The present overview is intended to point the readers' attention to the important subject of calcium orthophosphates. This type of materials is of special significance for human beings, because they represent the inorganic part of major normal (bones, teeth and antlers) and pathological (i.e., those appearing due to various diseases) calcified tissues of mammals. For example, atherosclerosis results in blood vessel blockage caused by a solid composite of cholesterol with calcium orthophosphates, while dental caries and osteoporosis mean a partial decalcification of teeth and bones, respectively, that results in replacement of a less soluble and harder biological apatite by more soluble and softer calcium hydrogenphosphates. Therefore, the processes of both normal and pathological calcifications are just an in vivo crystallization of calcium orthophosphates. Similarly, dental caries and osteoporosis might be considered an in vivo dissolution of calcium orthophosphates. Thus, calcium orthophosphates hold a great significance for humankind, and in this paper, an overview on the current knowledge on this subject is provided.

Postprandial endothelial dysfunction: role of glucose, lipids and insulin.

PubMed

Nitenberg, A; Cosson, E; Pham, I

2006-09-01

Endothelium plays a key role in the regulation of vascular tone and development of atherosclerosis. Endothelial function is impaired early in patients with risk factors and endothelial dysfunction is a strong and independent predictor of cardiovascular events. Because in normal subjects blood concentrations of glucose, lipids and insulin are increased after each meals, and postprandial changes last a long time after the meals, these changes might be of importance in the process of atherosclerosis initiation and development. Experimental and human studies have shown that a transient increase of blood concentrations of glucose, triglycerides and fatty acids, and insulin are able to depress endothelium-dependent vasodilation in healthy subjects and that hyperglycemia, hypertriglyceridemia and hyperinsulinemia are generator of reactive oxygen species at the origin of a cascade of pathophysiological events resulting in the activation of nuclear factor-kappaB. Nuclear factor-kappaB is an ubiquitous transcription factor controlling the expression of numerous genes and is involved in immunity, inflammation, regulation of cell proliferation and growth and apoptosis. These mechanisms may be involved in the development of atherosclerosis in normal subjects when food intake is chronically modified towards glucids and lipids with cumulative effects both on depression of endothelium dependent dilation and oxidative stress.

Development of Vision Based Multiview Gait Recognition System with MMUGait Database

PubMed Central

Ng, Hu; Tan, Wooi-Haw; Tong, Hau-Lee

2014-01-01

This paper describes the acquisition setup and development of a new gait database, MMUGait. This database consists of 82 subjects walking under normal condition and 19 subjects walking with 11 covariate factors, which were captured under two views. This paper also proposes a multiview model-based gait recognition system with joint detection approach that performs well under different walking trajectories and covariate factors, which include self-occluded or external occluded silhouettes. In the proposed system, the process begins by enhancing the human silhouette to remove the artifacts. Next, the width and height of the body are obtained. Subsequently, the joint angular trajectories are determined once the body joints are automatically detected. Lastly, crotch height and step-size of the walking subject are determined. The extracted features are smoothened by Gaussian filter to eliminate the effect of outliers. The extracted features are normalized with linear scaling, which is followed by feature selection prior to the classification process. The classification experiments carried out on MMUGait database were benchmarked against the SOTON Small DB from University of Southampton. Results showed correct classification rate above 90% for all the databases. The proposed approach is found to outperform other approaches on SOTON Small DB in most cases. PMID:25143972

Effects of varied doses of psilocybin on time interval reproduction in human subjects.

PubMed

Wackermann, Jirí; Wittmann, Marc; Hasler, Felix; Vollenweider, Franz X

2008-04-11

Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5s. The effects were assessed by parameter kappa of the 'dual klepsydra' model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates kappa were in the same order of magnitude as in earlier studies. In both experiments, kappa was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

Heightened sexual interest and sleep disturbance

NASA Technical Reports Server (NTRS)

Zarcone, V.; De La Pena, A.; Dement, W. C.

1974-01-01

The study demonstrates a behavioral effect of selective sleep disturbance in normal human subjects. Ten male subjects were selectively REM-deprived for two nights by awakening them at the onset of REM sleep. In addition, there were baseline and non-REM awakening conditions. Heightened sexual interest was defined by the number of film frames (using a Mackworth camera) in which subjects fixated on parts of the female figure in photographs. The largest mean difference in sexual interest was found between baseline and REM-deprivation. Both the non-REM awakenings and REM-sleep deprivation enhanced sexual interest. The failure to demonstrate a significant difference between REM-deprivation and non-REM awakenings may be due to the fact that subjects were REM-sleep-deprived in both conditions. It is suggested that REM-sleep loss may lead to increased selective attention and preoccupation with any cues which are usually interesting.

Tryptophan, kynurenine, and kynurenine metabolites: Relationship to lifetime aggression and inflammatory markers in human subjects

PubMed Central

Coccaro, Emil F.; Lee, Royce; Fanning, Jennifer R.; Fuchs, Dietmar; Goiny, Michel; Erhardt, Sophie; Christensen, Kyle; Brundin, Lena; Coussons-Read, Mary

2017-01-01

Inflammatory proteins are thought to be causally involved in the generation of aggression, possibly due to direct effects of cytokines in the central nervous system and/or by generation of inflammatory metabolites along the tryptophan-kynurenine (TRP/KYN) pathway, including KYN and its active metabolites kynurenic acid (KA), quinolinic acid (QA), and picolinic acid (PA). We examined plasma levels of TRP, KYN, KA, QA, and PA in 172 medication-free, medically healthy, human subjects to determine if plasma levels of these substances are altered as a function of trait aggression, and if they correlate with current plasma levels of inflammatory markers. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble interleukin-1 receptor-II (sIL-1RII) protein were also available in these subjects. We found normal levels of TRP but reduced plasma levels of KYN (by 48%), QA (by 6%), and a QA/KA (by 5%) ratio in subjects with Intermittent Explosive Disorder (IED) compared to healthy controls and psychiatric controls. Moreover, the metabolites were not associated with any of the inflammatory markers studied. These data do not support the hypothesis that elevated levels of KYN metabolites would be present in plasma of subjects with IED, and associated with plasma inflammation. However, our data do point to a dysregulation of the KYN pathway metabolites in these subjects. Further work will be necessary to replicate these findings and to understand their role in inflammation and aggression in these subjects. PMID:27318828

Out of sight, out of mind: Categorization learning and normal aging.

PubMed

Schenk, Sabrina; Minda, John P; Lech, Robert K; Suchan, Boris

2016-10-01

The present combined EEG and eye tracking study examined the process of categorization learning at different age ranges and aimed to investigate to which degree categorization learning is mediated by visual attention and perceptual strategies. Seventeen young subjects and ten elderly subjects had to perform a visual categorization task with two abstract categories. Each category consisted of prototypical stimuli and an exception. The categorization of prototypical stimuli was learned very early during the experiment, while the learning of exceptions was delayed. The categorization of exceptions was accompanied by higher P150, P250 and P300 amplitudes. In contrast to younger subjects, elderly subjects had problems in the categorization of exceptions, but showed an intact categorization performance for prototypical stimuli. Moreover, elderly subjects showed higher fixation rates for important stimulus features and higher P150 amplitudes, which were positively correlated with the categorization performances. These results indicate that elderly subjects compensate for cognitive decline through enhanced perceptual and attentional processing of individual stimulus features. Additionally, a computational approach has been applied and showed a transition away from purely abstraction-based learning to an exemplar-based learning in the middle block for both groups. However, the calculated models provide a better fit for younger subjects than for elderly subjects. The current study demonstrates that human categorization learning is based on early abstraction-based processing followed by an exemplar-memorization stage. This strategy combination facilitates the learning of real world categories with a nuanced category structure. In addition, the present study suggests that categorization learning is affected by normal aging and modulated by perceptual processing and visual attention. Copyright © 2016 Elsevier Ltd. All rights reserved.

Direct recordings from the auditory cortex in a cochlear implant user.

PubMed

Nourski, Kirill V; Etler, Christine P; Brugge, John F; Oya, Hiroyuki; Kawasaki, Hiroto; Reale, Richard A; Abbas, Paul J; Brown, Carolyn J; Howard, Matthew A

2013-06-01

Electrical stimulation of the auditory nerve with a cochlear implant (CI) is the method of choice for treatment of severe-to-profound hearing loss. Understanding how the human auditory cortex responds to CI stimulation is important for advances in stimulation paradigms and rehabilitation strategies. In this study, auditory cortical responses to CI stimulation were recorded intracranially in a neurosurgical patient to examine directly the functional organization of the auditory cortex and compare the findings with those obtained in normal-hearing subjects. The subject was a bilateral CI user with a 20-year history of deafness and refractory epilepsy. As part of the epilepsy treatment, a subdural grid electrode was implanted over the left temporal lobe. Pure tones, click trains, sinusoidal amplitude-modulated noise, and speech were presented via the auxiliary input of the right CI speech processor. Additional experiments were conducted with bilateral CI stimulation. Auditory event-related changes in cortical activity, characterized by the averaged evoked potential and event-related band power, were localized to posterolateral superior temporal gyrus. Responses were stable across recording sessions and were abolished under general anesthesia. Response latency decreased and magnitude increased with increasing stimulus level. More apical intracochlear stimulation yielded the largest responses. Cortical evoked potentials were phase-locked to the temporal modulations of periodic stimuli and speech utterances. Bilateral electrical stimulation resulted in minimal artifact contamination. This study demonstrates the feasibility of intracranial electrophysiological recordings of responses to CI stimulation in a human subject, shows that cortical response properties may be similar to those obtained in normal-hearing individuals, and provides a basis for future comparisons with extracranial recordings.

Spatial Nonuniformity of the Resting CBF and BOLD Responses to Sevoflurane: In Vivo Study of Normal Human Subjects With Magnetic Resonance Imaging

PubMed Central

Qiu, Maolin; Ramani, Ramachandran; Swetye, Michael; Constable, Robert Todd

2009-01-01

Pulsed arterial spin labeling magnetic resonance imaging (MRI) was performed to investigate the local coupling between resting regional cerebral blood flow (rCBF) and BOLD (blood oxygen level dependent) signal changes in 22 normal human subjects during the administration of 0.25 MAC (minimum alveolar concentration) sevoflurane. Two states were compared with subjects at rest: anesthesia and no-anesthesia. Regions of both significantly increased and decreased resting-state rCBF were observed. Increases were limited primarily to subcortical structures and insula, whereas, decreases were observed primarily in neocortical regions. No significant change was found in global CBF (gCBF). By simultaneously measuring rCBF and BOLD, region-specific anesthetic effects on the coupling between rCBF and BOLD were identified. Multiple comparisons of the agent-induced rCBF and BOLD changes demonstrated significant (P < 0.05) spatial variability in rCBF–BOLD coupling. The slope of the linear regression line for AC, where rCBF was increased by sevoflurane, was markedly smaller than the slope for those ROIs where rCBF was decreased by sevoflurane, indicating a bigger change in BOLD per unit change in rCBF in regions where rCBF was increased by sevoflurane. These results suggest that it would be inaccurate to use a global quantitative model to describe coupling across all brain regions and in all anesthesia conditions. The observed spatial nonuniformity of rCBF and BOLD signal changes suggests that any interpretation of BOLD fMRI data in the presence of an anesthetic requires consideration of these insights. PMID:17948882

High-speed adaptive optics line scan confocal retinal imaging for human eye

PubMed Central

Wang, Xiaolin; Zhang, Yuhua

2017-01-01

Purpose Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. Methods A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye’s optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. Results The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. Conclusions We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss. PMID:28257458

High-speed adaptive optics line scan confocal retinal imaging for human eye.

PubMed

Lu, Jing; Gu, Boyu; Wang, Xiaolin; Zhang, Yuhua

2017-01-01

Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye's optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss.

Identification of walking human model using agent-based modelling

NASA Astrophysics Data System (ADS)

Shahabpoor, Erfan; Pavic, Aleksandar; Racic, Vitomir

2018-03-01

The interaction of walking people with large vibrating structures, such as footbridges and floors, in the vertical direction is an important yet challenging phenomenon to describe mathematically. Several different models have been proposed in the literature to simulate interaction of stationary people with vibrating structures. However, the research on moving (walking) human models, explicitly identified for vibration serviceability assessment of civil structures, is still sparse. In this study, the results of a comprehensive set of FRF-based modal tests were used, in which, over a hundred test subjects walked in different group sizes and walking patterns on a test structure. An agent-based model was used to simulate discrete traffic-structure interactions. The occupied structure modal parameters found in tests were used to identify the parameters of the walking individual's single-degree-of-freedom (SDOF) mass-spring-damper model using 'reverse engineering' methodology. The analysis of the results suggested that the normal distribution with the average of μ = 2.85Hz and standard deviation of σ = 0.34Hz can describe human SDOF model natural frequency. Similarly, the normal distribution with μ = 0.295 and σ = 0.047 can describe the human model damping ratio. Compared to the previous studies, the agent-based modelling methodology proposed in this paper offers significant flexibility in simulating multi-pedestrian walking traffics, external forces and simulating different mechanisms of human-structure and human-environment interaction at the same time.

Speaker normalization for chinese vowel recognition in cochlear implants.

PubMed

Luo, Xin; Fu, Qian-Jie

2005-07-01

Because of the limited spectra-temporal resolution associated with cochlear implants, implant patients often have greater difficulty with multitalker speech recognition. The present study investigated whether multitalker speech recognition can be improved by applying speaker normalization techniques to cochlear implant speech processing. Multitalker Chinese vowel recognition was tested with normal-hearing Chinese-speaking subjects listening to a 4-channel cochlear implant simulation, with and without speaker normalization. For each subject, speaker normalization was referenced to the speaker that produced the best recognition performance under conditions without speaker normalization. To match the remaining speakers to this "optimal" output pattern, the overall frequency range of the analysis filter bank was adjusted for each speaker according to the ratio of the mean third formant frequency values between the specific speaker and the reference speaker. Results showed that speaker normalization provided a small but significant improvement in subjects' overall recognition performance. After speaker normalization, subjects' patterns of recognition performance across speakers changed, demonstrating the potential for speaker-dependent effects with the proposed normalization technique.

Scaling and the frequency dependence of Nyquist plot maxima of the electrical impedance of the human thigh.

PubMed

Shiffman, Carl

2017-11-30

To define and elucidate the properties of reduced-variable Nyquist plots. Non-invasive measurements of the electrical impedance of the human thigh. A retrospective analysis of the electrical impedances of 154 normal subjects measured over the past decade shows that 'scaling' of the Nyquist plots for human thigh muscles is a property shared by healthy thigh musculature, irrespective of subject and the length of muscle segment. Here the term scaling signifies the near and sometimes 'perfect' coalescence of the separate X versus R plots into one 'reduced' Nyquist plot by the simple expedient of dividing R and X by X m , the value of X at the reactance maximum. To the extent allowed by noise levels one can say that there is one 'universal' reduced Nyquist plot for the thigh musculature of healthy subjects. There is one feature of the Nyquist curves which is not 'universal', however, namely the frequency f m at which the maximum in X is observed. That is found to vary from 10 to 100 kHz. depending on subject and segment length. Analysis shows, however, that the mean value of 1/f m is an accurately linear function of segment length, though there is a small subject-to-subject random element as well. Also, following the recovery of an otherwise healthy victim of ankle fracture demonstrates the clear superiority of measurements above about 800 kHz, where scaling is not observed, in contrast to measurements below about 400 kHz, where scaling is accurately obeyed. The ubiquity of 'scaling' casts new light on the interpretation of impedance results as they are used in electrical impedance myography and bioelectric impedance analysis.

Mechanical work as an indirect measure of subjective costs influencing human movement.

PubMed

Zelik, Karl E; Kuo, Arthur D

2012-01-01

To descend a flight of stairs, would you rather walk or fall? Falling seems to have some obvious disadvantages such as the risk of pain or injury. But the preferred strategy of walking also entails a cost for the use of active muscles to perform negative work. The amount and distribution of work a person chooses to perform may, therefore, reflect a subjective valuation of the trade-offs between active muscle effort and other costs, such as pain. Here we use a simple jump landing experiment to quantify the work humans prefer to perform to dissipate the energy of landing. We found that healthy normal subjects (N = 8) preferred a strategy that involved performing 37% more negative work than minimally necessary (P<0.001) across a range of landing heights. This then required additional positive work to return to standing rest posture, highlighting the cost of this preference. Subjects were also able to modulate the amount of landing work, and its distribution between active and passive tissues. When instructed to land softly, they performed 76% more work than necessary (P<0.001), with a higher proportion from active muscles (89% vs. 84%, P<0.001). Stiff-legged landings, performed by one subject for demonstration, exhibited close to the minimum of work, with more of it performed passively through soft tissue deformations (at least 30% in stiff landings vs. 16% preferred). During jump landings, humans appear not to minimize muscle work, but instead choose to perform a consistent amount of extra work, presumably to avoid other subjective costs. The degree to which work is not minimized may indirectly quantify the relative valuation of costs that are otherwise difficult to measure.

Glial dysfunction in abstinent methamphetamine abusers

PubMed Central

Sailasuta, Napapon; Abulseoud, Osama; Harris, Kent C; Ross, Brian D

2010-01-01

Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized 13C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P>0.1). However, glial 13C-bicarbonate production rate from [1-13C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 μmol/g per min (N=5) versus controls 0.11 μmol/g per min (N=5), P=0.001). This is equivalent to 36% of the normal glial TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises 10% of total cerebral metabolic rate may impact operation of the neuronal glial glutamate cycle and result in accumulation of frontal brain glutamate, as observed in these recovering methamphetamine abusers. Although these are the first studies to define directly an abnormality in glial metabolism in human methamphetamine abuse, sequential studies using analogous 13C MRS methods may determine ‘cause and effect' between glial failure and neuronal injury. PMID:20040926

A Comprehensive Repository of Normal and Tumor Human Breast Tissues and Cells

DTIC Science & Technology

1999-07-01

mother was reported to have had cancer of the uterine cervix at the age of 22. Both maternal grandparents had died of colon cancer in their sixties...1 mutation). The repository also includes breast epithelial and stromal cell strains derived from non cancerous breast tissue as well as peripheral...tissue banks. 14. SUBJECT TERMS Breast Cancer 17. SECURITY CLASSIFICATION OF REPORT Unclassified 18. SECURITY CLASSIFICATION OF THIS PAGE

Studies of the Ability to Hold the Eye in Eccentric Gaze: Measurements in Normal Subjects with the Head Erect

NASA Technical Reports Server (NTRS)

Reschke, Millard F.; Somers, Jeffrey T.; Feiveson, Alan H.; Leigh, R. John; Wood, Scott J.; Paloski, William H.; Kornilova, Ludmila

2006-01-01

We studied the ability to hold the eyes in eccentric horizontal or vertical gaze angles in 68 normal humans, age range 19-56. Subjects attempted to sustain visual fixation of a briefly flashed target located 30 in the horizontal plane and 15 in the vertical plane in a dark environment. Conventionally, the ability to hold eccentric gaze is estimated by fitting centripetal eye drifts by exponential curves and calculating the time constant (t(sub c)) of these slow phases of gazeevoked nystagmus. Although the distribution of time-constant measurements (t(sub c)) in our normal subjects was extremely skewed due to occasional test runs that exhibited near-perfect stability (large t(sub c) values), we found that log10(tc) was approximately normally distributed within classes of target direction. Therefore, statistical estimation and inference on the effect of target direction was performed on values of z identical with log10t(sub c). Subjects showed considerable variation in their eyedrift performance over repeated trials; nonetheless, statistically significant differences emerged: values of tc were significantly higher for gaze elicited to targets in the horizontal plane than for the vertical plane (P less than 10(exp -5), suggesting eccentric gazeholding is more stable in the horizontal than in the vertical plane. Furthermore, centrifugal eye drifts were observed in 13.3, 16.0 and 55.6% of cases for horizontal, upgaze and downgaze tests, respectively. Fifth percentile values of the time constant were estimated to be 10.2 sec, 3.3 sec and 3.8 sec for horizontal, upward and downward gaze, respectively. The difference between horizontal and vertical gazeholding may be ascribed to separate components of the velocity position neural integrator for eye movements, and to differences in orbital mechanics. Our statistical method for representing the range of normal eccentric gaze stability can be readily applied in a clinical setting to patients who were exposed to environments that may have modified their central integrators and thus require monitoring. Patients with gaze-evoked nystagmus can be flagged by comparing to the above established normative criteria.

Novel approach to ambulatory assessment of human segmental orientation on a wearable sensor system.

PubMed

Liu, Kun; Liu, Tao; Shibata, Kyoko; Inoue, Yoshio; Zheng, Rencheng

2009-12-11

A new method using a double-sensor difference based algorithm for analyzing human segment rotational angles in two directions for segmental orientation analysis in the three-dimensional (3D) space was presented. A wearable sensor system based only on triaxial accelerometers was developed to obtain the pitch and yaw angles of thigh segment with an accelerometer approximating translational acceleration of the hip joint and two accelerometers measuring the actual accelerations on the thigh. To evaluate the method, the system was first tested on a 2 degrees of freedom mechanical arm assembled out of rigid segments and encoders. Then, to estimate the human segmental orientation, the wearable sensor system was tested on the thighs of eight volunteer subjects, who walked in a straight forward line in the work space of an optical motion analysis system at three self-selected speeds: slow, normal and fast. In the experiment, the subject was assumed to walk in a straight forward way with very little trunk sway, skin artifacts and no significant internal/external rotation of the leg. The root mean square (RMS) errors of the thigh segment orientation measurement were between 2.4 degrees and 4.9 degrees during normal gait that had a 45 degrees flexion/extension range of motion. Measurement error was observed to increase with increasing walking speed probably because of the result of increased trunk sway, axial rotation and skin artifacts. The results show that, without integration and switching between different sensors, using only one kind of sensor, the wearable sensor system is suitable for ambulatory analysis of normal gait orientation of thigh and shank in two directions of the segment-fixed local coordinate system in 3D space. It can then be applied to assess spatio-temporal gait parameters and monitoring the gait function of patients in clinical settings.

Gaze-stabilizing deficits and latent nystagmus in monkeys with brief, early-onset visual deprivation: eye movement recordings.

PubMed

Tusa, R J; Mustari, M J; Burrows, A F; Fuchs, A F

2001-08-01

The normal development and the capacity to calibrate gaze-stabilizing systems may depend on normal vision during infancy. At the end of 1 yr of dark rearing, cats have gaze-stabilizing deficits similar to that of the newborn human infant including decreased monocular optokinetic nystagmus (OKN) in the nasal to temporal (N-T) direction and decreased velocity storage in the vestibuloocular reflex (VOR). The purpose of this study is to determine to what extent restricted vision during the first 2 mo of life in monkeys affects the development of gaze-stabilizing systems. The eyelids of both eyes were sutured closed in three rhesus monkeys (Macaca mulatta) at birth. Eyelids were opened at 25 days in one monkey and 40 and 55 days in the other two animals. Eye movements were recorded from each eye using scleral search coils. The VOR, OKN, and fixation were examined at 6 and 12 mo of age. We also examined ocular alignment, refraction, and visual acuity in these animals. At 1 yr of age, visual acuity ranged from 0.3 to 0.6 LogMAR (20/40-20/80). All animals showed a defect in monocular OKN in the N-T direction. The velocity-storage component of OKN (i.e., OKAN) was the most impaired. All animals had a mild reduction in VOR gain but had a normal time constant. The animals deprived for 40 and 55 days had a persistent strabismus. All animals showed a nystagmus similar to latent nystagmus (LN) in human subjects. The amount of LN and OKN defect correlated positively with the duration of deprivation. In addition, the animal deprived for 55 days demonstrated a pattern of nystagmus similar to congenital nystagmus in human subjects. We found that restricted visual input during the first 2 mo of life impairs certain gaze-stabilizing systems and causes LN in primates.

Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.

PubMed

Kuo, Anderson H; Li, Cun; Li, Jinqi; Huber, Hillary F; Nathanielsz, Peter W; Clarke, Geoffrey D

2017-02-15

Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group and sex (with P < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non-human primate model. Further studies across the life span will determine progression of cardiac dysfunction. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Identification of novel inhibitors of human Chk1 using pharmacophore-based virtual screening and their evaluation as potential anti-cancer agents

NASA Astrophysics Data System (ADS)

Kumar, Vikash; Khan, Saman; Gupta, Priyanka; Rastogi, Namrata; Mishra, Durga Prasad; Ahmed, Shakil; Siddiqi, Mohammad Imran

2014-12-01

Kinases are one of the major players in cancer development and progression. Serine threonine kinases such as human checkpoint kinase-1 (Chk1), Mek1 and cyclin-dependent kinases have been identified as promising targets for cancer treatment. Chk1 is an important kinase with vital role in cell cycle arrest and many potent inhibitors targeted to Chk1 have been reported and few are currently in clinical trials. Considering the emerging importance of Chk1 inhibitors in cancer treatment there is a need to widen the chemical space of Chk1 inhibitors. In this study, we are reporting an integrated in silico approach to identify novel competitive Chk1 inhibitors. A 4-features pharmacophore model was derived from a co-crystallized structure of known potent Chk1 inhibitor and subjected to screen Maybridge compound library. Hits obtained from the screening were docked into the Chk1 active site and filtered on the basis of docking score and the number of pharmacophoric features showing conserved interaction within the active site of Chk1. Further, five compounds from the top ranking hits were subjected to in vitro evaluation as Chk1 inhibitor. After the kinase assay, four compounds were found to be active against human Chk1 (IC50 range from 4.2 to 12.5 µM). Subsequent study using the cdc25-22 mutant yeast cells revealed that one of compound (SPB07479; IC50 = 4.24 µM) promoted the formation of multinucleated cells, therefore overriding the cell cycle checkpoint. Validation studies using normal and human cancer cell lines, indicated that SPB07479 significantly inhibited proliferation of cervical cancer cells as a single agent and chemosensitized glioma and pancreatic cancer cell lines to standard chemotherapy while sparing normal cells. Additionally SPB07479 did not show significant cytotoxicity in normal cells. In conclusion we report that SPB07479 appear promising for further development of Chk1 inhibitors. This study also highlights the role of conserved water molecules in the active site of Chk1 for the successful identification of novel inhibitors.

Experimental studies of breaking of elastic tired wheel under variable normal load

NASA Astrophysics Data System (ADS)

Fedotov, A. I.; Zedgenizov, V. G.; Ovchinnikova, N. I.

2017-10-01

The paper analyzes the braking of a vehicle wheel subjected to disturbances of normal load variations. Experimental tests and methods for developing test modes as sinusoidal force disturbances of the normal wheel load were used. Measuring methods for digital and analogue signals were used as well. Stabilization of vehicle wheel braking subjected to disturbances of normal load variations is a topical issue. The paper suggests a method for analyzing wheel braking processes under disturbances of normal load variations. A method to control wheel baking processes subjected to disturbances of normal load variations was developed.

Outcome analysis of individualized vestibular rehabilitation protocols

NASA Technical Reports Server (NTRS)

Black, F. O.; Angel, C. R.; Pesznecker, S. C.; Gianna, C.

2000-01-01

OBJECTIVE: To determine the outcome of vestibular rehabilitation protocols in subjects with peripheral vestibular disorders compared with normal and abnormal control subjects. STUDY DESIGN: Prospective study using repeated measure, matched control design. Subjects were solicited consecutively according to these criteria: vestibular disorder subjects who had abnormal results of computerized dynamic posturography (CDP) sensory organization tests (SOTs) 5 and 6 and underwent rehabilitation; vestibular disorder subjects who had abnormal results of SOTs 5 and 6 and did not undergo rehabilitation; and normal subjects (normal SOTs). SETTING: Tertiary neurotology clinic. SUBJECTS: Men and women over age 18 with chronic vestibular disorders and chief complaints of unsteadiness, imbalance, and/or motion intolerance, and normal subjects. INTERVENTIONS: Pre- and post-rehabilitation assessment included CDP, vestibular disability, and activities of daily living questionnaires. Individualized rehabilitation plans were designed and implemented to address the subject's specific complaints and functional deficits. Supervised sessions were held at weekly intervals, and self-administered programs were devised for daily home use. MAIN OUTCOME MEASURES: CDP composite and SOT scores, number of falls on CDP, and self-assessment questionnaire results. RESULTS: Subjects who underwent rehabilitation (Group A) showed statistically significant improvements in SOTs, overall composite score, and reduction in falls compared with abnormal (Group B) control groups. Group A's performances after rehabilitation were not significantly different from those of normal subjects (Group C) in SOTs 3 through 6, and close to normal on SOTs 1 and 2. Subjects in Group A also reported statistically significant symptomatic improvement. CONCLUSIONS: Outcome measures of vestibular protocol physical therapy confirmed objective and subjective improvement in subjects with chronic peripheral vestibular disorders. These findings support results reported by other investigators.

Increased regional cerebral blood flow but normal distribution of GABAA receptor in the visual cortex of subjects with early-onset blindness.

PubMed

Mishina, Masahiro; Senda, Michio; Kiyosawa, Motohiro; Ishiwata, Kiichi; De Volder, Anne G; Nakano, Hideki; Toyama, Hinako; Oda, Kei-ichi; Kimura, Yuichi; Ishii, Kenji; Sasaki, Touru; Ohyama, Masashi; Komaba, Yuichi; Kobayashi, Shirou; Kitamura, Shin; Katayama, Yasuo

2003-05-01

Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.

Two-dimensional electrophoretic profiling of normal human kidney glomerulus proteome and construction of an extensible markup language (XML)-based database.

PubMed

Yoshida, Yutaka; Miyazaki, Kenji; Kamiie, Junichi; Sato, Masao; Okuizumi, Seiji; Kenmochi, Akihisa; Kamijo, Ken'ichi; Nabetani, Takuji; Tsugita, Akira; Xu, Bo; Zhang, Ying; Yaoita, Eishin; Osawa, Tetsuo; Yamamoto, Tadashi

2005-03-01

To contribute to physiology and pathophysiology of the glomerulus of human kidney, we have launched a proteomic study of human glomerulus, and compiled a profile of proteins expressed in the glomerulus of normal human kidney by two-dimensional gel electrophoresis (2-DE) and identification with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Kidney cortices with normal appearance were obtained from patients under surgical nephrectomy due to renal tumor, and glomeruli were highly purified by a standard sieving method followed by picking-up under a phase-contrast microscope. The glomerular proteins were separated by 2-DE with 24 cm immobilized pH gradient strips in the 3-10 range in the first dimension and 26 x 20 cm sodium dodecyl sulfate polyacrylamide electrophoresis gels of 12.5% in the second dimension. Gels were silver-stained, and valid spots were processed for identification through an integrated robotic system that consisted of a spot picker, an in-gel digester, and a MALDI-TOF MS and / or a LC-MS/MS. From 2-DE gel images of glomeruli of four subjects with no apparent pathologic manifestations, a synthetic gel image of normal glomerular proteins was created. The synthetic gel image contained 1713 valid spots, of which 1559 spots were commonly observed in the respective 2-DE gels. Among the 1559 spots, 347 protein spots, representing 212 proteins, have so far been identified, and used for the construction of an extensible markup language (XML)-based database. The database is deposited on a web site (http://www.sw.nec.co.jp/bio/rd/hgldb/index.html) in a form accessible to researchers to contribute to proteomic studies of human glomerulus in health and disease.

Comparison of range of motion and function of subjects with reverse anatomy Bayley-Walker shoulder replacement with those of normal subjects.

PubMed

Masjedi, Milad; Lovell, Cara; Johnson, Garth R

2011-12-01

Patients with rotator cuff tear and degenerative shoulder joint disease commonly experience severe pain and reduced performance during activities of daily living. A popular way to treat these patients is by means of reverse anatomy shoulder prosthesis. Studying the kinematics of subjects with reverse anatomy implant would be useful in order to gain knowledge about functionality of different designs. It is hypothesized that the kinematics of these subjects, in the absence of rotator cuff muscles, differs from that of normal subjects. In this study the upper limb kinematics of 12 subjects with a Bayley-Walker reverse anatomy shoulder prosthesis while performing tasks common in everyday activities and those that represent the range of motion was analyzed and compared to that of 12 normal subjects. Each patient also completed an Oxford Shoulder Score. Substantial reduction in the Bayley-Walker subjects' ranges of motion was observed compared to normal subjects. The mean abduction angle decreased from 109° (±20) for normal subjects to 64° (±25). A similar trend was observed during flexion and axial rotation tasks. Furthermore, the normal group showed less variable ranges of motion performing the standard tasks, whereas for the prosthetic group this varied greatly, which is likely to be dependent on muscle strength. Although the decreased range of motion was prominent, subjects were able to complete most of the tasks by compensating with their elbow and trunk. The most challenging task for Bayley-Walker subjects was lifting an object to head height. Copyright © 2010 Elsevier B.V. All rights reserved.

Cerebral activation evoked by the mirror illusion of the hand in stroke patients compared to normal subjects.

PubMed

Wang, Jing; Fritzsch, Claire; Bernarding, Johannes; Krause, Thomas; Mauritz, Karl-Heinz; Brunetti, Maddalena; Dohle, Christian

2013-01-01

Mirror therapy (MT) was found to improve motor function after stroke, but its neural mechanisms remain unclear, especially in single stroke patients. The following imaging study was designed to compare brain activation patterns evoked by the mirror illusion in single stroke patients with normal subjects. Fifteen normal volunteers and five stroke patients with severe arm paresis were recruited. Cerebral activations during movement mirroring by means of a video chain were recorded with functional magnetic resonance imaging (fMRI). Single-subject analysis was performed using SPM 8. For normal subjects, ten and thirteen subjects displayed lateralized cerebral activations evoked by the mirror illusion while moving their right and left hand respectively. The magnitude of this effect in the precuneus contralateral to the seen hand was not dependent on movement speed or subjective experience. Negative correlation of activation strength with age was found for the right hand only. The activation pattern in stroke patients is comparable to that of normal subjects and present in four out of five patients. In summary, the mirror illusion can elicit cerebral activation contralateral to the perceived hand in the majority of single normal subjects, but not in all of them. This is similar even in stroke patients with severe hemiparesis.

Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry.

PubMed

Li, Bing; Sheng, Minjie; Xie, Liqi; Liu, Feng; Yan, Guoquan; Wang, Weifang; Lin, Anjuan; Zhao, Fei; Chen, Yihui

2014-01-09

Diabetes mellitus has been shown to be associated with and complicated by dry eye syndrome. We sought to examine and compare the tear film proteome of type 2 diabetic patients with or without dry eye syndrome and normal subjects using two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry (MS)-based proteomics. Tears were collected from eight type 2 diabetes patients with dry eye syndrome, eight type 2 diabetes patients without dry eye syndrome, and eight normal subjects. Tear breakup time (BUT) was determined, and tear proteins were prepared and analyzed using two-dimensional strong cation-exchange/reversed-phase nano-scale liquid chromatography MS. All MS/MS spectra were identified by using SEQUEST against the human International Protein Index (IPI) database and the relative abundance of individual proteins was assessed by spectral counting. Tear BUT was significantly lower in patients with diabetes and dry eye syndrome than in patients with diabetes only and normal subjects. Analysis of spectral counts of tear proteins showed that, compared to healthy controls, patients with diabetes and dry eye syndrome had increased expression of apoptosis-related proteins, like annexin A1, and immunity- and inflammation-related proteins, including neutrophil elastase 2 and clusterin, and glycometabolism-related proteins, like apolipoprotein A-II. Dry eye syndrome in diabetic patients is associated with aberrant expression of tear proteins, and the findings could lead to identification of novel pathways for therapeutic targeting and new diagnostic markers.

Results of the first-in-human clinical trial for MB-102, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Debreczeny, Martin P.; Dowling, Thomas C.

2015-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated MB-102, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in progress. This clinical trial is the first in a series of trials necessary to obtain regulatory clearance from the FDA. We report herein the comparison of plasma pharmacokinetics between MB-102 and the known standard exogenous GFR agent Iohexol in healthy subjects with normal renal function. Post simultaneous administration of both agents, blood samples over a period of 12 hours were collected from each subject to assess pharmacokinetic parameters including GFR. Urine samples were collected over this same period to assess percent injected dose recovered in the urine. Results indicate MB-102 is a GFR agent in humans from the comparison to the standard agent.

A model of fluid and solute exchange in the human: validation and implications.

PubMed

Bert, J L; Gyenge, C C; Bowen, B D; Reed, R K; Lund, T

2000-11-01

In order to understand better the complex, dynamic behaviour of the redistribution and exchange of fluid and solutes administered to normal individuals or to those with acute hypovolemia, mathematical models are used in addition to direct experimental investigation. Initial validation of a model developed by our group involved data from animal experiments (Gyenge, C.C., Bowen, B.D., Reed, R.K. & Bert, J.L. 1999b. Am J Physiol 277 (Heart Circ Physiol 46), H1228-H1240). For a first validation involving humans, we compare the results of simulations with a wide range of different types of data from two experimental studies. These studies involved administration of normal saline or hypertonic saline with Dextran to both normal and 10% haemorrhaged subjects. We compared simulations with data including the dynamic changes in plasma and interstitial fluid volumes VPL and VIT respectively, plasma and interstitial colloid osmotic pressures PiPL and PiIT respectively, haematocrit (Hct), plasma solute concentrations and transcapillary flow rates. The model predictions were overall in very good agreement with the wide range of experimental results considered. Based on the conditions investigated, the model was also validated for humans. We used the model both to investigate mechanisms associated with the redistribution and transport of fluid and solutes administered following a mild haemorrhage and to speculate on the relationship between the timing and amount of fluid infusions and subsequent blood volume expansion.

Quantitative Structure-Cytotoxicity Relationship of Oleoylamides.

PubMed

Sakagami, Hiroshi; Uesawa, Yoshihiro; Ishihara, Mariko; Kagaya, Hajime; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Takao, Koichi; Sugita, Yoshiaki

2015-10-01

Eighteen oleoylamides were subjected to quantitative structure-activity relationship analysis based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to assess their biological activities. Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and five human oral normal cells (gingival fibroblast, periodontal ligament fibroblast, pulp cell, oral keratinocyte, primary gingival epithelial cells) was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor-selectivity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against normal human oral cells to that against OSCC cell lines. Potency-selectivity expression (PSE) was determined by the ratio of TS to CC50 against OSCC. Anti-HIV activity was evaluated by the ratio of CC50 to the concentration leading to 50% cytoprotection from HIV infection (EC50). Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method. Among 18 derivatives, compounds 8: with a catechol group) and 18: with a (2-pyridyl)amino group) had the highest TS. On the other hand, doxorubicin and 5-fluorouracil (5-FU) were more highly cytotoxic to normal epithelial cells, displaying unexpectedly lower TS and PSE values. None of the compounds had anti-HIV activity. Among 330 chemical descriptors, 75, 73 and 19 descriptors significantly correlated to the cytotoxicity to normal and tumor cells, and TS, respectively. Multivariate statistics with chemical descriptors for molecular polarization and hydrophobicity may be useful for the evaluation of cytotoxicity and TS of oleoylamides. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Gastrocnemius mitochondrial respiration: are there any differences between men and women?

PubMed

Thompson, Jonathan R; Swanson, Stanley A; Casale, George P; Johanning, Jason M; Papoutsi, Evlampia; Koutakis, Panagiotis; Miserlis, Dimitrios; Zhu, Zhen; Pipinos, Iraklis I

2013-11-01

Work on human and mouse skeletal muscle by our group and others has demonstrated that aging and age-related degenerative diseases are associated with mitochondrial dysfunction, which may be more prevalent in males. There have been, however, no studies that specifically examine the influence of male or female sex on human skeletal muscle mitochondrial respiration. The purpose of this study was to compare mitochondrial respiration in the gastrocnemius of adult men and women. Gastrocnemius muscle was obtained from male (n = 19) and female (n = 11) human subjects with healthy lower-extremity musculoskeletal and arterial systems and normal ambulatory function. All patients were undergoing operations for the treatment of varicose veins in their legs. Mitochondrial respiration was determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Complex I-, II-, III-, and IV-dependent respiration was measured individually and normalized to muscle weight, total protein content, and citrate synthase (CS, index of mitochondrial content). Male and female patients had no evidence of musculoskeletal or arterial disease and did not differ with regard to age, race, body mass index, or other clinical characteristics. Complex I-, II-, III-, and IV-dependent respiration normalized to muscle weight, total protein content, and CS did not statistically differ for males compared with females. Our study evaluates, for the first time, gastrocnemius mitochondrial respiration of adult men and women who have healthy musculoskeletal and arterial systems and normal ambulatory function. Our data demonstrate there are no differences in the respiration of gastrocnemius mitochondria between men and women. Copyright © 2013 Elsevier Inc. All rights reserved.

Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects.

PubMed

Reyna, Sara M; Ghosh, Sangeeta; Tantiwong, Puntip; Meka, C S Reddy; Eagan, Phyllis; Jenkinson, Christopher P; Cersosimo, Eugenio; Defronzo, Ralph A; Coletta, Dawn K; Sriwijitkamol, Apiradee; Musi, Nicolas

2008-10-01

OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IkappaB/NFkappaB via TLR4 and whether FFAs increase TLR4 expression/content in muscle. RESULTS- Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IkappaBalpha content, an indication of elevated IkappaB/NFkappaB signaling. The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IkappaB/NFkappaB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IkappaB/NFkappaB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.

Suppression tuning of distortion-product otoacoustic emissions: Results from cochlear mechanics simulation

PubMed Central

Liu, Yi-Wen; Neely, Stephen T.

2013-01-01

This paper presents the results of simulating the acoustic suppression of distortion-product otoacoustic emissions (DPOAEs) from a computer model of cochlear mechanics. A tone suppressor was introduced, causing the DPOAE level to decrease, and the decrement was plotted against an increasing suppressor level. Suppression threshold was estimated from the resulting suppression growth functions (SGFs), and suppression tuning curves (STCs) were obtained by plotting the suppression threshold as a function of suppressor frequency. Results show that the slope of SGFs is generally higher for low-frequency suppressors than high-frequency suppressors, resembling those obtained from normal hearing human ears. By comparing responses of normal (100%) vs reduced (50%) outer-hair-cell sensitivities, the model predicts that the tip-to-tail difference of the STCs correlates well with that of intra-cochlear iso-displacement tuning curves. The correlation is poorer, however, between the sharpness of the STCs and that of the intra-cochlear tuning curves. These results agree qualitatively with what was recently reported from normal-hearing and hearing-impaired human subjects, and examination of intra-cochlear model responses can provide the needed insight regarding the interpretation of DPOAE STCs obtained in individual ears. PMID:23363112

Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin

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

Mintun, M.A.; Dennis, D.R.; Welch, M.J.

1987-11-01

We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-(/sup 68/Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of (/sup 68/Ga)citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escapemore » rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury.« less

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

PubMed Central

Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

2016-01-01

Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

Effect of laryngeal anesthesia on pulmonary function testing in normal subjects.

PubMed

Kuna, S T; Woodson, G E; Sant'Ambrogio, G

1988-03-01

Pulmonary function tests (PFT) were performed on 11 normal subjects before and after topical anesthesia of the larynx. The PFT consisted of flow volume loops and body box determinations of functional residual capacity and airway resistance, each performed in triplicate. After the first set of tests, cotton pledgets soaked in 4% lidocaine were held in the pyriform sinuses for 2 min to block the superior laryngeal nerves. In addition, 1.5 ml of 10% cocaine was dropped on the vocal cords via indirect laryngoscopy. PFT were repeated 5 min after anesthesia. Besides routine analysis of the flow volume loops, areas under the inspiratory (Area I) and expiratory (Area E) portions of the loops were calculated by planimetry. Area I, peak inspiratory flow (PIF), as well as forced inspiratory flow at 25, 50, and 75% forced vital capacity (FVC), decreased after anesthesia. Peak expiratory flow decreased after anesthesia, but Area E and forced expiratory flow at 25, 50, and 75% FVC were unchanged. This protocol also was performed in 12 normal subjects with isotonic saline being substituted for the lidocaine and cocaine. In this group, no significant differences were observed when flow volume loop parameters were compared before and after topical application of saline. In 5 spontaneously breathing anesthetized dogs, posterior cricoarytenoid muscle and afferent superior laryngeal nerve activity were recorded before and after laryngeal anesthesia performed with the same procedure used in the human subjects. Laryngeal anesthesia resulted in a substantial decrease or a complete disappearance of afferent SLN activity recorded during unobstructed and obstructed respiration. The data suggest that laryngeal receptors help modulate upper airway patency in man.

Cytokine and chemokine levels in tears from healthy subjects.

PubMed

Carreño, Ester; Enríquez-de-Salamanca, Amalia; Tesón, Marisa; García-Vázquez, Carmen; Stern, Michael E; Whitcup, Scott M; Calonge, Margarita

2010-11-01

There is growing evidence for the existence of an 'immune tone' in normal tears. The aim of this study was to determine the levels of a large panel of cytokines and chemokines in tears obtained from healthy subjects. These levels can then serve as baseline values for comparison with patients suffering from ocular surface diseases. Nine healthy subjects participated in this study, and normal ocular surface health was documented by the results of a dry eye questionnaire, Schirmer strip wetting, and vital staining of the cornea. Four microliters of tears were collected from each eye and analysed separately with multiplex bead-based assays for the concentration of 30 cytokines and chemokines. Twenty-five cytokines/chemokines were detected. CCL11/Eotaxin1, GM-CSF, G-CSF, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-10, IL-13, IL-12p70, IL-15, CX3CL1/Fractalkine, TNF-α, epidermal growth factor, and CCL4/MIP-1β were present at 5-100 pg/ml. IL-1β, IL-6, IL-7A, CXCL8/IL-8, and CCL2/MCP-1 were present at 100-400 pg/ml. IL-1Ra, CXCL10/IP-10 and vascular endothelial growth factor were present at more than 1000 pg/ml. Multiplex bead-based assays are convenient for cytokine/chemokine detection in tears. Fracktalkine has been detected in human healthy tears for the first time. The knowledge of cytokine/chemokine concentrations in tears from normal subjects is an important reference for further comparison with patients suffering from ocular surface diseases. Variability in their levels can reflect a phenomenon of potential importance for the understanding of the ocular surface cytokine pattern. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

Metabolism of dietary sulphate: absorption and excretion in humans.

PubMed Central

Florin, T; Neale, G; Gibson, G R; Christl, S U; Cummings, J H

1991-01-01

Dietary sulphate may affect colonic pathophysiology because sulphate availability determines in part the activity of sulphate reducing bacteria in the bowel. The main product of sulphate reducing bacterial oxidative metabolism, hydrogen sulphide, is potentially toxic. Although it is generally believed that the sulphate ion is poorly absorbed, there are no available data on how much sulphate reaches the colon nor on the relative contributions from diet and endogenous sources. To resolve these questions, balance studies were performed on six healthy ileostomists and three normal subjects chosen because they did not have detectable sulphate reducing bacteria in their faeces. The subjects were fed diets which varied in sulphate content from 1.6-16.6 mmol/day. Sulphate was measured in diets, faeces (ileal effluent in ileostomists), and urine by anion exchange chromatography with conductivity detection. Overall there was net absorption of dietary sulphate, with the absorptive capacity of the gastrointestinal tract plateauing at 5 mmol/day in the ileostomists and exceeding 16 mmol/day in the normal subjects. Endogenous secretion of sulphate in the upper gastrointestinal tract was from 0.96-2.6 mmol/day. The dietary contribution to the colonic sulphate pool ranged up to 9 mmol/day, there being linear identity between diet and upper gastrointestinal losses for intakes above 7 mmol/day. Faecal losses of sulphate were trivial (less than 0.5 mmol/day) in the normal subjects at all doses. It is concluded that diet and intestinal absorption are the principal factors affecting the amounts of sulphate reaching the colon. Endogenous secretion of sulphate by colonic mucosa may also be important in determining amounts of sulphate in the colon. PMID:1855683

Information processing deficits in psychiatric populations: Implications for normal workload assessment

NASA Technical Reports Server (NTRS)

Harvey, Philip D.

1988-01-01

In one study, schizophrenics, bipolar manics, and mentally normal individuals were administered a digit recall task. The total performance of schizophrenics looked much like that of a normal processor under a higher load level. The manics' performance was intermediate. Primary performance was particularly poor among the mentally ill subjects. In a second study, three groups in the same populations as in the first study were asked to shadow and recall verbatim eight descriptive text passages. Distraction effects were found for schizophrenics only in the areas of percentage of words correctly shadowed and recall variables; the two areas were not correlated, however. It appears that, for schizophrenics, distraction disrupts the ability to effectively shadow information to a greater extent than it disrupts the ability to encode information for recall. The two studies imply that capacity-carrying abnormalities that affect the quantity but not the quality of information processing can be useful in pointing to information processing of normal humans under high load conditions.

Physiologic and Genetic Evidence Links Hemopexin to Triglycerides in Mice and Humans

PubMed Central

Lawson, Heather A; Zayed, Mohamed; Wayhart, Jessica P; Fabbrini, Elisa; Love-Gregory, Latisha; Klein, Samuel; Semenkovich, Clay F

2017-01-01

Background/Objectives Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. Subjects/Methods Hemopexin was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F16 advanced intercross between the LG/J and SM/J strains of mice. Hpx expression was evaluated in both reproductive fatpads and livers of mice representing three strains, LG/J (n = 25), SM/J (n = 27) and C57Bl/6J (n = 19), on high- and low-fat diets. The effect of altered Hpx expression on adipogenesis was studied in 3T3-L1 cells. Circulating HPX protein along with HPX expression were characterized in subcutaneous white adipose tissue samples obtained from a cohort of metabolically abnormal (n = 18) and of metabolically normal (n = 24) obese human subjects. We further examined the relationship between HPX and triglycerides in human atherosclerotic plaques (n = 18). Results Hemopexin expression in mouse adipose tissue, but not liver, was regulated by dietary fat regardless of genetic background. Hemopexin increased in concert with adipogenesis in 3T3-L1 cells, and disruption of its expression impaired adipocyte differentiation. RNAseq data from the adipose tissue of obese humans showed differential expression of hemopexin based on metabolic disease status (p < 0.05), and circulating hemopexin levels were correlated with serum triglycerides in these subjects (r = 0.33; p = 0.03). Hemopexin was also found in an unbiased proteomic screen of human atherosclerotic plaques, and shown to display differential abundance based on extent of disease and triglyceride content (p < 0.05). Conclusions Our findings suggest that hemopexin is associated with triglycerides and provide a framework for understanding mechanisms underlying lipid metabolism and metabolic disease. PMID:28119529

The Gap Detection Test: Can It Be Used to Diagnose Tinnitus?

PubMed

Boyen, Kris; Başkent, Deniz; van Dijk, Pim

2015-01-01

Animals with induced tinnitus showed difficulties in detecting silent gaps in sounds, suggesting that the tinnitus percept may be filling the gap. The main purpose of this study was to evaluate the applicability of this approach to detect tinnitus in human patients. The authors first hypothesized that gap detection would be impaired in patients with tinnitus, and second, that gap detection would be more impaired at frequencies close to the tinnitus frequency of the patient. Twenty-two adults with bilateral tinnitus, 20 age-matched and hearing loss-matched subjects without tinnitus, and 10 young normal-hearing subjects participated in the study. To determine the characteristics of the tinnitus, subjects matched an external sound to their perceived tinnitus in pitch and loudness. To determine the minimum detectable gap, the gap threshold, an adaptive psychoacoustic test was performed three times by each subject. In this gap detection test, four different stimuli, with various frequencies and bandwidths, were presented at three intensity levels each. Similar to previous reports of gap detection, increasing sensation level yielded shorter gap thresholds for all stimuli in all groups. Interestingly, the tinnitus group did not display elevated gap thresholds in any of the four stimuli. Moreover, visual inspection of the data revealed no relation between gap detection performance and perceived tinnitus pitch. These findings show that tinnitus in humans has no effect on the ability to detect gaps in auditory stimuli. Thus, the testing procedure in its present form is not suitable for clinical detection of tinnitus in humans.

Endocannabinoids Measurement in Human Saliva as Potential Biomarker of Obesity

PubMed Central

Tabarin, Antoine; Clark, Samantha; Leste-Lasserre, Thierry; Marsicano, Giovanni; Piazza, Pier Vincenzo; Cota, Daniela

2012-01-01

Background The discovery of the endocannabinoid system and of its role in the regulation of energy balance has significantly advanced our understanding of the physiopathological mechanisms leading to obesity and type 2 diabetes. New knowledge on the role of this system in humans has been acquired by measuring blood endocannabinoids. Here we explored endocannabinoids and related N-acylethanolamines in saliva and verified their changes in relation to body weight status and in response to a meal or to body weight loss. Methodology/Principal Findings Fasting plasma and salivary endocannabinoids and N-acylethanolamines were measured through liquid mass spectrometry in 12 normal weight and 12 obese, insulin-resistant subjects. Salivary endocannabinoids and N-acylethanolamines were evaluated in the same cohort before and after the consumption of a meal. Changes in salivary endocannabinoids and N-acylethanolamines after body weight loss were investigated in a second group of 12 obese subjects following a 12-weeks lifestyle intervention program. The levels of mRNAs coding for enzymes regulating the metabolism of endocannabinoids, N-acylethanolamines and of cannabinoid type 1 (CB1) receptor, alongside endocannabinoids and N-acylethanolamines content, were assessed in human salivary glands. The endocannabinoids 2-arachidonoylglycerol (2-AG), N-arachidonoylethanolamide (anandamide, AEA), and the N-acylethanolamines (oleoylethanolamide, OEA and palmitoylethanolamide, PEA) were quantifiable in saliva and their levels were significantly higher in obese than in normal weight subjects. Fasting salivary AEA and OEA directly correlated with BMI, waist circumference and fasting insulin. Salivary endocannabinoids and N-acylethanolamines did not change in response to a meal. CB1 receptors, ligands and enzymes were expressed in the salivary glands. Finally, a body weight loss of 5.3% obtained after a 12-weeks lifestyle program significantly decreased salivary AEA levels. Conclusions/Significance Endocannabinoids and N-acylethanolamines are quantifiable in saliva and their levels correlate with obesity but not with feeding status. Body weight loss significantly decreases salivary AEA, which might represent a useful biomarker in obesity. PMID:22860123

Model of reticuloendothelial iron metabolism in humans: Abnormal behavior in idiopathic hemochromatosis and in inflammation

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

Fillet, G.; Beguin, Y.; Baldelli, L.

1989-08-01

Iron transport in the reticuloendothelial (RE) system plays a central role in iron metabolism, but its regulation has not been characterized physiologically in vivo in humans. In particular, why serum iron is elevated and RE cells are much less iron-loaded than parenchymal cells in idiopathic hemochromatosis is not known. The processing of erythrocyte iron by the RE system was studied after intravenous (IV) injection of 59Fe heat-damaged RBCs (HDRBCs) and 55Fe transferrin in normal subjects and in patients with iron deficiency, idiopathic hemochromatosis, inflammation, marrow aplasia, or hyperplastic erythropoiesis. Early release of 59Fe by the RE system was calculated frommore » the plasma iron turnover and the 59Fe plasma reappearance curve. Late release was calculated from the ratio of 59Fe/55Fe RBC utilization in 2 weeks. The partitioning of iron between the early (release from heme catabolism) and late (release from RE stores) phases depended on the size of RE iron stores, as illustrated by the inverse relationship observed between early release and plasma ferritin (P less than .001). There was a strong correlation between early release and the rate of change of serum iron levels during the first three hours in normal subjects (r = .85, P less than .001). Inflammation produced a blockade of the early release phase, whereas in idiopathic hemochromatosis early release was considerably increased as compared with subjects with similar iron stores. Based on these results, we describe a model of RE iron metabolism in humans. We conclude that the RE system appears to determine the diurnal fluctuations in serum iron levels through variations in the immediate output of heme iron. In idiopathic hemochromatosis, a defect of the RE cell in withholding iron freed from hemoglobin could be responsible for the high serum iron levels and low RE iron stores.« less

Assessment of the menstrual cycle upon total hemoglobin, water concentration, and oxygen saturation in the female breast

NASA Astrophysics Data System (ADS)

Jiang, Shudong; Pogue, Brian W.; Srinivasan, Subhadra; Soho, Sandra; Poplack, Steven P.; Tosteson, Tor D.; Paulsen, Keith D.

2003-07-01

Near-infrared imaging can be used in humans to characterize changes in breast tumor tissue by imaging total hemoglobin and water concentrations as well as oxygen saturation. In order to improve our understanding of these changes, we need to carefully quantify the range of variation possible in normal tissues for these parameters. In this study, the effect of the subject"s menstrual cycle was examined by imaging their breast at the follicular (7-14 days of the cycle) and secretory phases (21-28 days of the cycle), using our NIR tomographic system. In this system, a three layer patient interface is used to measure 3 planes along the breast from chest wall towards the nipple at 1cm increments. Seven volunteers in their 40s were observed for 2 menstrual cycles and all of these volunteers recently had normal mammograms (ACR 1) with heterogeneously dense breast composition. The results show that average total hemoglobin in the breast increased in many subjects between 0 to 15% from the follicular phase to secretory phase. Oxygen saturation and water concentration changes between these 2 parts of the cycle were between -6.5% to 12% for saturation and between -33% to 28% for water concentration. While the data averaged between subjects showed no significant change existed between phases, it was clear that individual subjects did exhibit changes in composition which were consistent from cycle to cycle. Understanding what leads to this heterogeneity between subjects will be an important factor in utilizing these measurements in clinical practice.

Effect of magnetic micropulsations on the biological systems — A bioenvironmental study

NASA Astrophysics Data System (ADS)

Subrahmanyam, S.; Narayan, P. V. Sanker; Srinivasan, T. M.

1985-09-01

During the last decade considerable interest has been evinced by scientists on the possible influence of earth's electromagnetic environment on human and animal physiology. While some studies on this topic have been reported from high magnetic latitudes — USSR and central Europe — no work has been done in very low latitude and equatorial regions. The present study, undertaken to fill this gap, has been carried out at the low latitude of Madras (Magnetic Dip ≅ 10°). Pulsating magnetic fields in the frequency range of 0.01 Hz to 20 Hz and with amplitudes of ±5 and ±50 gamma were impressed on test animals, normal human subjects and Yoga practitioners lying supine inside a 4-member Fanselau-Braunbeck coil system with the heads oriented in the four cardinal directions with respect to earth's magnetic field. The entire set of exposures of the test animals and humans was given under two ambient magnetic fields namely, against full local geomagnetic field of about 40,000 gamma and half this value. In the animals ECG, EEG, Tail Blood Flow and Respiration were recorded continuously on a polygraph. The biochemical tests carried out were postprandial blood sugar, serum cholesterol and plasma cortisol. Neurochemical assays of Noradrenaline, Adrenaline, Dopamine, Serotonin and 5 Hydroxy Indole Acetic acid were done on the brain tissue, myocardium and adrenal glands, immediately after complete set of exposures of the animals in all four orientations. Motor activity and rectal temperature were also noted before and after the exposures. The ‘Control’ animals were also subjected to exactly the same investigations as the test animals without, however, exposing them to the magnetic fields. These observations revealed some decisive changes in certain parameters for certain frequencies of the impressed field and also in specific orientations of the test animals. Similar studies carried out on normal human subjects and practitioners of Yoga and Meditation, also showed certain decisive changes in the electrophysiology, neurochemistry and biochemistry when oriented to North and East. The North orientation appeared to induce inhibition of brain electrical activity and associated neurochemical and biochemical changes, whereas the East orientation showed a response of calm, blissful alertness.

Human's Capability to Discriminate Spatial Forces at the Big Toe.

PubMed

Hagengruber, Annette; Höppner, Hannes; Vogel, Jörn

2018-01-01

A key factor for reliable object manipulation is the tactile information provided by the skin of our hands. As this sensory information is so essential in our daily life it should also be provided during teleoperation of robotic devices or in the control of myoelectric prostheses. It is well-known that feeding back the tactile information to the user can lead to a more natural and intuitive control of robotic devices. However, in some applications it is difficult to use the hands as natural feedback channels since they may already be overloaded with other tasks or, e.g., in case of hand prostheses not accessible at all. Many alternatives for tactile feedback to the human hand have already been investigated. In particular, one approach shows that humans can integrate uni-directional (normal) force feedback at the toe into their sensorimotor-control loop. Extending this work, we investigate the human's capability to discriminate spatial forces at the bare front side of their toe. A state-of-the-art haptic feedback device was used to apply forces with three different amplitudes-2 N, 5 N, and 8 N-to subjects' right big toes. During the experiments, different force stimuli were presented, i.e., direction of the applied force was changed, such that tangential components occured. In total the four directions up (distal), down (proximal), left (medial), and right (lateral) were tested. The proportion of the tangential force was varied corresponding to a directional change of 5° to 25° with respect to the normal force. Given these force stimuli, the subjects' task was to identify the direction of the force change. We found the amplitude of the force as well as the proportion of tangential forces to have a significant influence on the success rate. Furthermore, the direction right showed a significantly different successrate from all other directions. The stimuli with a force amplitude of 8 N achieved success rates over 89% in all directions. The results of the user study provide evidence that the subjects were able to discriminate spatial forces at their toe within defined force amplitudes and tangential proportion.

Human's Capability to Discriminate Spatial Forces at the Big Toe

PubMed Central

Hagengruber, Annette; Höppner, Hannes; Vogel, Jörn

2018-01-01

A key factor for reliable object manipulation is the tactile information provided by the skin of our hands. As this sensory information is so essential in our daily life it should also be provided during teleoperation of robotic devices or in the control of myoelectric prostheses. It is well-known that feeding back the tactile information to the user can lead to a more natural and intuitive control of robotic devices. However, in some applications it is difficult to use the hands as natural feedback channels since they may already be overloaded with other tasks or, e.g., in case of hand prostheses not accessible at all. Many alternatives for tactile feedback to the human hand have already been investigated. In particular, one approach shows that humans can integrate uni-directional (normal) force feedback at the toe into their sensorimotor-control loop. Extending this work, we investigate the human's capability to discriminate spatial forces at the bare front side of their toe. A state-of-the-art haptic feedback device was used to apply forces with three different amplitudes—2 N, 5 N, and 8 N—to subjects' right big toes. During the experiments, different force stimuli were presented, i.e., direction of the applied force was changed, such that tangential components occured. In total the four directions up (distal), down (proximal), left (medial), and right (lateral) were tested. The proportion of the tangential force was varied corresponding to a directional change of 5° to 25° with respect to the normal force. Given these force stimuli, the subjects' task was to identify the direction of the force change. We found the amplitude of the force as well as the proportion of tangential forces to have a significant influence on the success rate. Furthermore, the direction right showed a significantly different successrate from all other directions. The stimuli with a force amplitude of 8 N achieved success rates over 89% in all directions. The results of the user study provide evidence that the subjects were able to discriminate spatial forces at their toe within defined force amplitudes and tangential proportion. PMID:29692718

Light microscopic localization of calcitonin gene-related peptide in the normal feline trigeminal system and following retrogasserian rhizotomy.

PubMed

Henry, M A; Johnson, L R; Nousek-Goebl, N; Westrum, L E

1996-02-19

Calcitonin gene-related peptide (CGRP) is a neuropeptide that has been implicated in the transmission and modulation of primary afferent nociceptive stimuli. In this study, we describe the light microscopic distribution of CGRP immunoreactivity (IR) within the feline trigeminal ganglion and trigeminal nucleus of normal adult subjects and in subjects 10 and 30 days following complete retrogasserian rhizotomy. Within the trigeminal ganglion of normal subjects, cell bodies and fibers showed CGRP-IR, whereas immunoreactive fibers were rare in the central root region. Within the normal spinal trigeminal and main sensory nuclei, CGRP-IR was seen to form a reproducible pattern that varied between the different nuclei. Following rhizotomy, most, but not all, of the CGRP-IR was lost from the spinal trigeminal and main sensory nuclei, except in regions where the upper cervical roots and cranial nerves VII, IX and X project into the trigeminal nucleus. The pattern seen at 10 days contained more CGRP-IR than that seen at 30 days and suggests that degenerating fibers still show CGRP-IR. In contrast to the decrease seen in the nuclei after rhizotomy, examination of the central root that was still attached to the trigeminal ganglion showed an increase in CGRP-IR within fibers, some of which ended in growth conelike enlargements. Rhizotomy induced a dramatic increase in CGRP-IR within trigeminal motoneurons and their fibers, which was strongest 10 days after rhizotomy and weaker at 30 days, which was still stronger than normal. These results indicate that the majority of CGRP-IR found in the trigeminal nucleus originates from trigeminal primary afferents and that an upregulation of CGRP-IR occurs in trigeminal motoneurons and in regenerating fibers in the part of the central root that was still attached to the ganglion. In addition, the persistence of CGRP-IR fibers in the trigeminal nucleus provides one possible explanation for the preservation of pain in humans following trigeminal rhizotomy.

Blood glucose may condition factor VII levels in diabetic and normal subjects.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Torella, R

1988-12-01

Increased factor VII levels have been reported in Type 1 (insulin-dependent) diabetic subjects. A direct correlation between fasting plasma glucose and factor VII level was found to exist in both diabetic and normal subjects. Induced-hyperglycaemia was able to increase factor VII levels in both diabetic patients and normal control subjects while, when euglycaemia was achieved in diabetic patients, factor VII values returned to normal range. This study shows that the level of factor VII may be directly conditioned by circulating blood glucose and, therefore, stresses the role of hyperglycaemia in conditioning coagulation abnormalities in diabetes mellitus.

Human organ-on-a-chip BioMEMS devices for testing new diagnostic and therapeutic strategies

NASA Astrophysics Data System (ADS)

Leary, James F.; Key, Jaehong; Vidi, Pierre-Alexandre; Cooper, Christy L.; Kole, Ayeeshik; Reece, Lisa M.; Lelièvre, Sophie A.

2013-03-01

MEMS human "organs-on-a-chip" can be used to create model human organ systems for developing new diagnostic and therapeutic strategies. They represent a promising new strategy for rapid testing of new diagnostic and therapeutic approaches without the need for involving risks to human subjects. We are developing multicomponent, superparamagnetic and fluorescent nanoparticles as X-ray and MRI contrast agents for noninvasive multimodal imaging and for antibody- or peptide-targeted drug delivery to tumor and precancerous cells inside these artificial organ MEMS devices. Magnetic fields can be used to move the nanoparticles "upstream" to find their target cells in an organs-on-achip model of human ductal breast cancer. Theoretically, unbound nanoparticles can then be removed by reversing the magnetic field to give a greatly enhanced image of tumor cells within these artificial organ structures. Using branched PDMS microchannels and 3D tissue engineering of normal and malignant human breast cancer cells inside those MEMS channels, we can mimic the early stages of human ductal breast cancer with the goal to improve the sensitivity and resolution of mammography and MRI of very small tumors and test new strategies for treatments. Nanomedical systems can easily be imaged by multicolor confocal microscopy inside the artificial organs to test targeting and therapeutic responses including the differential viability of normal and tumor cells during treatments. Currently we are using 2-dimensional MEMS structures, but these studies can be extended to more complex 3D structures using new 3D printing technologies.

Voluntary suppression of hyperthermia-induced hyperventilation mitigates the reduction in cerebral blood flow velocity during exercise in the heat.

PubMed

Tsuji, Bun; Honda, Yasushi; Ikebe, Yusuke; Fujii, Naoto; Kondo, Narihiko; Nishiyasu, Takeshi

2015-04-15

Hyperthermia during prolonged exercise leads to hyperventilation, which can reduce arterial CO2 pressure (PaCO2 ) and, in turn, cerebral blood flow (CBF) and thermoregulatory response. We investigated 1) whether humans can voluntarily suppress hyperthermic hyperventilation during prolonged exercise and 2) the effects of voluntary breathing control on PaCO2 , CBF, sweating, and skin blood flow. Twelve male subjects performed two exercise trials at 50% of peak oxygen uptake in the heat (37°C, 50% relative humidity) for up to 60 min. Throughout the exercise, subjects breathed normally (normal-breathing trial) or they tried to control their minute ventilation (respiratory frequency was timed with a metronome, and target tidal volumes were displayed on a monitor) to the level reached after 5 min of exercise (controlled-breathing trial). Plotting ventilatory and cerebrovascular responses against esophageal temperature (Tes) showed that minute ventilation increased linearly with rising Tes during normal breathing, whereas controlled breathing attenuated the increased ventilation (increase in minute ventilation from the onset of controlled breathing: 7.4 vs. 1.6 l/min at +1.1°C Tes; P < 0.001). Normal breathing led to decreases in estimated PaCO2 and middle cerebral artery blood flow velocity (MCAV) with rising Tes, but controlled breathing attenuated those reductions (estimated PaCO2 -3.4 vs. -0.8 mmHg; MCAV -10.4 vs. -3.9 cm/s at +1.1°C Tes; P = 0.002 and 0.011, respectively). Controlled breathing had no significant effect on chest sweating or forearm vascular conductance (P = 0.67 and 0.91, respectively). Our results indicate that humans can voluntarily suppress hyperthermic hyperventilation during prolonged exercise, and this suppression mitigates changes in PaCO2 and CBF. Copyright © 2015 the American Physiological Society.

Voluntary suppression of hyperthermia-induced hyperventilation mitigates the reduction in cerebral blood flow velocity during exercise in the heat

PubMed Central

Tsuji, Bun; Honda, Yasushi; Ikebe, Yusuke; Fujii, Naoto; Kondo, Narihiko

2015-01-01

Hyperthermia during prolonged exercise leads to hyperventilation, which can reduce arterial CO2 pressure (PaCO2) and, in turn, cerebral blood flow (CBF) and thermoregulatory response. We investigated 1) whether humans can voluntarily suppress hyperthermic hyperventilation during prolonged exercise and 2) the effects of voluntary breathing control on PaCO2, CBF, sweating, and skin blood flow. Twelve male subjects performed two exercise trials at 50% of peak oxygen uptake in the heat (37°C, 50% relative humidity) for up to 60 min. Throughout the exercise, subjects breathed normally (normal-breathing trial) or they tried to control their minute ventilation (respiratory frequency was timed with a metronome, and target tidal volumes were displayed on a monitor) to the level reached after 5 min of exercise (controlled-breathing trial). Plotting ventilatory and cerebrovascular responses against esophageal temperature (Tes) showed that minute ventilation increased linearly with rising Tes during normal breathing, whereas controlled breathing attenuated the increased ventilation (increase in minute ventilation from the onset of controlled breathing: 7.4 vs. 1.6 l/min at +1.1°C Tes; P < 0.001). Normal breathing led to decreases in estimated PaCO2 and middle cerebral artery blood flow velocity (MCAV) with rising Tes, but controlled breathing attenuated those reductions (estimated PaCO2 −3.4 vs. −0.8 mmHg; MCAV −10.4 vs. −3.9 cm/s at +1.1°C Tes; P = 0.002 and 0.011, respectively). Controlled breathing had no significant effect on chest sweating or forearm vascular conductance (P = 0.67 and 0.91, respectively). Our results indicate that humans can voluntarily suppress hyperthermic hyperventilation during prolonged exercise, and this suppression mitigates changes in PaCO2 and CBF. PMID:25632021

Lower Leg Injury Reference Values and Risk Curves from Survival Analysis for Male and Female Dummies: Meta-analysis of Postmortem Human Subject Tests.

PubMed

Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A; Banerjee, Anjishnu

2015-01-01

Derive lower leg injury risk functions using survival analysis and determine injury reference values (IRV) applicable to human mid-size male and small-size female anthropometries by conducting a meta-analysis of experimental data from different studies under axial impact loading to the foot-ankle-leg complex. Specimen-specific dynamic peak force, age, total body mass, and injury data were obtained from tests conducted by applying the external load to the dorsal surface of the foot of postmortem human subject (PMHS) foot-ankle-leg preparations. Calcaneus and/or tibia injuries, alone or in combination and with/without involvement of adjacent articular complexes, were included in the injury group. Injury and noninjury tests were included. Maximum axial loads recorded by a load cell attached to the proximal end of the preparation were used. Data were analyzed by treating force as the primary variable. Age was considered as the covariate. Data were censored based on the number of tests conducted on each specimen and whether it remained intact or sustained injury; that is, right, left, and interval censoring. The best fits from different distributions were based on the Akaike information criterion; mean and plus and minus 95% confidence intervals were obtained; and normalized confidence interval sizes (quality indices) were determined at 5, 10, 25, and 50% risk levels. The normalization was based on the mean curve. Using human-equivalent age as 45 years, data were normalized and risk curves were developed for the 50th and 5th percentile human size of the dummies. Out of the available 114 tests (76 fracture and 38 no injury) from 5 groups of experiments, survival analysis was carried out using 3 groups consisting of 62 tests (35 fracture and 27 no injury). Peak forces associated with 4 specific risk levels at 25, 45, and 65 years of age are given along with probability curves (mean and plus and minus 95% confidence intervals) for PMHS and normalized data applicable to male and female dummies. Quality indices increased (less tightness-of-fit) with decreasing age and risk level for all age groups and these data are given for all chosen risk levels. These PMHS-based probability distributions at different ages using information from different groups of researchers constituting the largest body of data can be used as human tolerances to lower leg injury from axial loading. Decreasing quality indices (increasing index value) at lower probabilities suggest the need for additional tests. The anthropometry-specific mid-size male and small-size female mean human risk curves along with plus and minus 95% confidence intervals from survival analysis and associated IRV data can be used as a first step in studies aimed at advancing occupant safety in automotive and other environments.

Do enteric neurons make hypocretin? ☆

PubMed Central

Baumann, Christian R.; Clark, Erika L.; Pedersen, Nigel P.; Hecht, Jonathan L.; Scammell, Thomas E.

2008-01-01

Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, sectioned tissue, pre-treatment of mice with colchicine, and the use of various primary antisera), we could not identify hypocretin-producing cells in enteric nervous tissue collected from mice or normal human subjects. These results raise doubts about whether enteric neurons produce hypocretin. PMID:18191238

Discriminative stimulus effects of caffeine and benzphetamine in amphetamine-trained volunteers.

PubMed

Chait, L D; Johanson, C E

1988-01-01

The discriminative stimulus (DS) and subjective effects of caffeine (100 and 300 mg, PO) and benzphetamine (12.5 and 50 mg, PO) were studied in 18 normal human volunteers trained to discriminate between d-amphetamine (10 mg) and placebo. d-Amphetamine increased ratings of drug liking and activity level and produced a profile of subjective effects characteristic of amphetamine and related psychomotor stimulants. The DS effects of d-amphetamine generalized only partially to caffeine and benzphetamine; mean percent d-amphetamine-appropriate responding was 42 and 58 after 100 and 300 mg caffeine, respectively, and 17 and 56 after 12.5 and 50 mg benzphetamine, respectively. Neither dose of caffeine affected ratings of drug liking or activity level, but 300 mg caffeine did produce a profile of subjective effects that partially overlapped with that produced by d-amphetamine. Benzphetamine 50 mg, but not 12.5 mg, increased ratings of drug liking and activity level and produced a profile of subjective effects qualitatively similar to, but weaker than, that produced by d-amphetamine. For both caffeine and benzphetamine, a close relationship was observed between their subjective effects and their ability to substitute for the DS effects of d-amphetamine. These results correspond well with findings obtained from similar studies conducted with laboratory animals, providing further support for the reliability and validity of human drug discrimination paradigms.

Cerebrospinal Fluid Concentration of Key Autophagy Protein Lamp2 Changes Little During Normal Aging

PubMed Central

Loeffler, David A.; Klaver, Andrea C.; Coffey, Mary P.; Aasly, Jan O.

2018-01-01

Autophagy removes both functional and damaged intracellular macromolecules from cells via lysosomal degradation. Three autophagic mechanisms, namely macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy, have been described in mammals. Studies in experimental systems have found macroautophagy and CMA to decrease with normal aging, despite the fact that oxidative stress, which can activate both processes, increases with normal aging. Whether autophagic mechanisms decrease in the human brain during normal aging is unclear. The primary objective of this study was to examine the association of a major autophagy protein, lysosome-associated membrane glycoprotein (lamp2), with age in cerebrospinal fluid (CSF) samples from healthy subjects. Lamp2 consists of three isoforms, lamp2a, 2b and 2c, all of which participate in autophagy. Lamp2’s CSF concentration decreases in Parkinson’s disease (PD) and increases in Alzheimer’s disease (AD), but whether its CSF concentration changes during normal aging has not been investigated. Our secondary objectives were to examine the associations of lamp2’s CSF concentration with CSF levels of the molecular chaperone heat shock 70-kDa protein (HSPA8), which interacts with lamp2a in CMA, and oxidative stress markers 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-isoprostane (8-ISO) and Total Antioxidant Capacity (TAC) in healthy subjects. We found lamp2’s observed associations with these variables to be weak, with all Kendall’s tau-b absolute values ≤0.20. These results suggest that CSF lamp2 concentration changes little during normal aging and does not appear to be associated with HSPA8 or oxidative stress. Further studies are indicated to determine the relationship between CSF lamp2 concentration and brain autophagic processes.

Color vision with rapid-onset acceleration.

PubMed

Balldin, U I; Derefeldt, G; Eriksson, L; Werchan, P M; Andersson, P; Yates, J T

2003-01-01

Only sporadic information exists concerning perceived color shifts at increased G-loads. The purpose of this study was to investigate whether or not color vision is affected by rapid onset high G7-loads up to +9 Gz, and specifically whether perception of hue changes. There were 10 male subjects, 9 with normal color vision and 1 with red-green protanomaly, all accustomed to Gz-loads in a human centrifuge. Each subject was tested on a total of 60 Gz-exposures with 10 s periods at +3, +5, +7, and +9 Gz in the centrifuge on three different days. G-onset rate was 6 G x s(-1). The subjects wore an anti-G suit and performed straining maneuvers if necessary to maintain vision. Five square color stimuli of medium saturation (yellow, red, blue, green, and gray) were projected one at a time on a screen in front of the subject, who gave his hue response orally. In 96.6% of exposures to various Gz-loads, the subjects responded by correctly naming colors. (The statistical analyses of the results were done for the subjects with normal color vision, with the protanomalous subject excluded.) Hue shifts occurred at the higher +Gz-levels, including 7.7% of the +9 Gz exposures. Yellow was the hue most frequently perceived as changed. Hue shifts were reported for yellow in 11% and 16% of the +7 and +9 Gz exposures, respectively. Hue shifts at +9 Gz occurred as frequently as blackout and G-LOC together. However, statistical analyses showed no significant effects for +Gz-load. Absolute identification of the color stimuli of medium saturation was stable and was not significantly affected by the rapid onset +Gz-loads up to and including +9 Gz.

Cardiovascular effects of vasopressin following V(1) receptor blockade compared to effects of nitroglycerin.

PubMed

Cooke, C R; Wall, B M; Huch, K M; Mangold, T

2001-09-01

Studies to more clearly determine the mechanisms associated with arginine vasopressin (AVP)-induced vasodilation were performed in normal subjects and in quadriplegic subjects with impaired efferent sympathetic responses. Studies to compare the effects of AVP with the hemodynamic effects of nitroglycerin, an agent that primarily affects venous capacitance vessels, were also performed in normal subjects. Incremental infusions of AVP following V(1)-receptor blockade resulted in equivalent reductions in systemic vascular resistance (SVRI) in normal and in quadriplegic subjects. However, there were major differences in the effect on mean arterial pressure (MAP), which was reduced in quadriplegic subjects but did not change in normal subjects. This difference in MAP can be attributed to a difference in the magnitude of increase in cardiac output (CI), which was twofold greater in normal than in quadriplegic subjects. These observations are consistent with AVP-induced vasodilation of arterial resistance vessels with reflex sympathetic enhancement of CI and are clearly different from the hemodynamic effects of nitroglycerin, i.e., reductions in MAP, CI, and indexes of cardiac preload, with only minor changes in SVRI.

Detection of cow's milk proteins and minor components in human milk using proteomics techniques.

PubMed

Coscia, A; Orrù, S; Di Nicola, P; Giuliani, F; Varalda, A; Peila, C; Fabris, C; Conti, A; Bertino, E

2012-10-01

Cow's milk proteins (CMPs) are the best characterized food allergens. The aim of this study was to investigate cow's milk allergens in human colostrum of term and preterm newborns' mothers, and other minor protein components by proteomics techniques, more sensitive than other techniques used in the past. Sixty-two term and 11 preterm colostrum samples were collected, subjected to a treatment able to increase the concentration of the most diluted proteins and simultaneously to reduce the concentration of the proteins present at high concentration (Proteominer Treatment), and subsequently subjected to the steps of proteomic techniques. The most relevant finding in this study was the detection of the intact bovine alpha-S1-casein in human colostrum, then bovine alpha-1-casein could be considered the cow's milk allergen that is readily secreted in human milk and could be a cause of sensitization to cow's milk in exclusively breastfed predisposed infants. Another interesting result was the detection, at very low concentrations, of proteins previously not described in human milk (galectin-7, the different isoforms of the 14-3-3 protein and the serum amyloid P-component), probably involved in the regulation of the normal cell growth, in the pro-apoptotic function and in the regulation of tissue homeostasis. Further investigations are needed to understand if these families of proteins have specific biological activity in human milk.

Extracting Information from Narratives: An Application to Aviation Safety Reports

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

Posse, Christian; Matzke, Brett D.; Anderson, Catherine M.

2005-05-12

Aviation safety reports are the best available source of information about why a flight incident happened. However, stream of consciousness permeates the narratives making difficult the automation of the information extraction task. We propose an approach and infrastructure based on a common pattern specification language to capture relevant information via normalized template expression matching in context. Template expression matching handles variants of multi-word expressions. Normalization improves the likelihood of correct hits by standardizing and cleaning the vocabulary used in narratives. Checking for the presence of negative modifiers in the proximity of a potential hit reduces the chance of false hits.more » We present the above approach in the context of a specific application, which is the extraction of human performance factors from NASA ASRS reports. While knowledge infusion from experts plays a critical role during the learning phase, early results show that in a production mode, the automated process provides information that is consistent with analyses by human subjects.« less

Common Genetic Variant in VIT Is Associated with Human Brain Asymmetry.

PubMed

Tadayon, Sayed H; Vaziri-Pashkam, Maryam; Kahali, Pegah; Ansari Dezfouli, Mitra; Abbassian, Abdolhossein

2016-01-01

Brain asymmetry varies across individuals. However, genetic factors contributing to this normal variation are largely unknown. Here we studied variation of cortical surface area asymmetry in a large sample of subjects. We performed principal component analysis (PCA) to capture correlated asymmetry variation across cortical regions. We found that caudal and rostral anterior cingulate together account for a substantial part of asymmetry variation among individuals. To find SNPs associated with this subset of brain asymmetry variation we performed a genome-wide association study followed by replication in an independent cohort. We identified one SNP (rs11691187) that had genome-wide significant association (P Combined = 2.40e-08). The rs11691187 is in the first intron of VIT. In a follow-up analysis, we found that VIT gene expression is associated with brain asymmetry in six donors of the Allen Human Brain Atlas. Based on these findings we suggest that VIT contributes to normal brain asymmetry variation. Our results can shed light on disorders associated with altered brain asymmetry.

Potential for Stable Flies and House Flies (Diptera: Muscidae) to Transmit Rift Valley Fever Virus

DTIC Science & Technology

2010-01-01

14. ABSTRACT Rift Valley fever ( RVF ), a disease of ruminants and humans, has been responsible for large outbreaks in Africa that have resulted in...regions. Although RVF virus (RVFV) is normally transmitted by mosquitoes, we wanted to determine the potential for this virus to replicate in 2 of...of a RVF outbreak. Other Stomoxys species present in Africa and elsewhere may also play similar roles. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION

Effect of arm swing strategy on local dynamic stability of human gait.

PubMed

Punt, Michiel; Bruijn, Sjoerd M; Wittink, Harriet; van Dieën, Jaap H

2015-02-01

Falling causes long term disability and can even lead to death. Most falls occur during gait. Therefore improving gait stability might be beneficial for people at risk of falling. Recently arm swing has been shown to influence gait stability. However at present it remains unknown which mode of arm swing creates the most stable gait. To examine how different modes of arm swing affect gait stability. Ten healthy young male subjects volunteered for this study. All subjects walked with four different arm swing instructions at seven different gait speeds. The Xsens motion capture suit was used to capture gait kinematics. Basic gait parameters, variability and stability measures were calculated. We found an increased stability in the medio-lateral direction with excessive arm swing in comparison to normal arm swing at all gait speeds. Moreover, excessive arm swing increased stability in the anterior-posterior and vertical direction at low gait speeds. Ipsilateral and inphase arm swing did not differ compared to a normal arm swing. Excessive arm swing is a promising gait manipulation to improve local dynamic stability. For excessive arm swing in the ML direction there appears to be converging evidence. The effect of excessive arm swing on more clinically relevant groups like the more fall prone elderly or stroke survivors is worth further investigating. Excessive arm swing significantly increases local dynamic stability of human gait. Copyright © 2014 Elsevier B.V. All rights reserved.

Haplotypes identified by 10 DNA restriction fragment length polymorphisms at the human low density lipoprotein receptor gene locus.

PubMed Central

Kotze, M J; Langenhoven, E; Retief, A E; Seftel, H C; Henderson, H E; Weich, H F

1989-01-01

Ten useful two allele restriction fragment length polymorphisms of the low density lipoprotein receptor gene were used for haplotype analysis in 45 unrelated familial hypercholesterolaemic (FH) patients, 60 normal controls, and 32 FH homozygotes, all of whom were white Afrikaners. Pedigree analysis in 27 informative heterozygous FH and 23 normal families has shown the segregation of at least 17 haplotypes in the normal population (111 chromosomes) compared to a predominant association of two of these haplotypes with the disease in the FH subjects. This association was further confirmed in 32 FH homozygotes, indicating at least two 'founder' members for the disease in the Afrikaner population. Recombination events were not detected in any of the families studied and we thus conclude that the haplotypes associated with FH function as specific markers for the disease and will allow presymptomatic diagnosis in affected families. PMID:2565980

Anisotropic analysis of trabecular architecture in human femur bone radiographs using quaternion wavelet transforms.

PubMed

Sangeetha, S; Sujatha, C M; Manamalli, D

2014-01-01

In this work, anisotropy of compressive and tensile strength regions of femur trabecular bone are analysed using quaternion wavelet transforms. The normal and abnormal femur trabecular bone radiographic images are considered for this study. The sub-anatomic regions, which include compressive and tensile regions, are delineated using pre-processing procedures. These delineated regions are subjected to quaternion wavelet transforms and statistical parameters are derived from the transformed images. These parameters are correlated with apparent porosity, which is derived from the strength regions. Further, anisotropy is also calculated from the transformed images and is analyzed. Results show that the anisotropy values derived from second and third phase components of quaternion wavelet transform are found to be distinct for normal and abnormal samples with high statistical significance for both compressive and tensile regions. These investigations demonstrate that architectural anisotropy derived from QWT analysis is able to differentiate normal and abnormal samples.

Comparison of single-microphone noise reduction schemes: can hearing impaired listeners tell the difference?

PubMed

Huber, Rainer; Bisitz, Thomas; Gerkmann, Timo; Kiessling, Jürgen; Meister, Hartmut; Kollmeier, Birger

2018-06-01

The perceived qualities of nine different single-microphone noise reduction (SMNR) algorithms were to be evaluated and compared in subjective listening tests with normal hearing and hearing impaired (HI) listeners. Speech samples added with traffic noise or with party noise were processed by the SMNR algorithms. Subjects rated the amount of speech distortions, intrusiveness of background noise, listening effort and overall quality, using a simplified MUSHRA (ITU-R, 2003 ) assessment method. 18 normal hearing and 18 moderately HI subjects participated in the study. Significant differences between the rating behaviours of the two subject groups were observed: While normal hearing subjects clearly differentiated between different SMNR algorithms, HI subjects rated all processed signals very similarly. Moreover, HI subjects rated speech distortions of the unprocessed, noisier signals as being more severe than the distortions of the processed signals, in contrast to normal hearing subjects. It seems harder for HI listeners to distinguish between additive noise and speech distortions or/and they might have a different understanding of the term "speech distortion" than normal hearing listeners have. The findings confirm that the evaluation of SMNR schemes for hearing aids should always involve HI listeners.

Dichotic listening in patients with situs inversus: brain asymmetry and situs asymmetry.

PubMed

Tanaka, S; Kanzaki, R; Yoshibayashi, M; Kamiya, T; Sugishita, M

1999-06-01

In order to investigate the relation between situs asymmetry and functional asymmetry of the human brain, a consonant-vowel syllable dichotic listening test known as the Standard Dichotic Listening Test (SDLT) was administered to nine subjects with situs inversus (SI) that ranged in age from 6 to 46 years old (mean of 21.8 years old, S.D. = 15.6); the four males and five females all exhibited strong right-handedness. The SDLT was also used to study twenty four age-matched normal subjects that were from 6 to 48 years old (mean 21.7 years old, S.D. = 15.3); the twelve males and twelve females were all strongly right-handed and served as a control group. Eight out of the nine subjects (88.9%) with SI more often reproduced the sounds from the right ear than sounds from the left ear; this is called right ear advantage (REA). The ratio of REA in the control group was almost the same, i.e., nineteen out of the twenty-four subjects (79.1%) showed REA. Results of the present study suggest that the left-right reversal in situs inversus does not involve functional asymmetry of the brain. As such, the system that produces functional asymmetry in the human brain must independently recognize laterality from situs asymmetry.

Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

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

Buchsbaum, M.S.; Wu, J.; Hazlett, E.

The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increasemore » in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep.« less

Low-dose caffeine physical dependence in humans.

PubMed

Griffiths, R R; Evans, S M; Heishman, S J; Preston, K L; Sannerud, C A; Wolf, B; Woodson, P P

1990-12-01

This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized.

Research ethics across the 49th parallel: the potential value of pilot testing "equivalent protections" in Canadian research institutions.

PubMed

Lavery, James V; McDonald, Michael; Meslin, Eric M

2005-01-01

Canada and the United States share the world's largest trade partnership and an increasing concern about divergent regulatory approaches to common industries. Canadian research institutes receive more research funding from the U.S. National Institutes of Health than any other country, much of it to fund multi-centre and collaborative research between the two countries. Because of these close economic and research ties, and the extensive similarities between the two countries in the review and oversight of ethics in human subjects research, we propose that Canada would be an ideal country for a pilot-test of the feasibility of "equivalent protections," a U.S. regulation that permits comparison of protections for human subjects between institutions in the two countries. The "equivalent protections" has been advocated by various bodies in the United States as a potentially beneficial mechanism for improving oversight of foreign trials. As well, we argue that "equivalent protections" could prove to be valuable for Canada in five specific ways: (1) by potentially reducing administrative burden on Canadian research institutions administering U.S. federal research funding; (2) by creating symbolic value of an explicit recognition by the United States that procedures normally followed for the protection of human subjects in Canadian research institutions are at least equivalent to those provided by the U.S. regulations; (3) by lowering the opportunity cost of investing in research in Canada; (4) by affording Canada an opportunity to enhance its leadership role in international research by offering an alternative to the U.S. regulatory model for the protection of human subjects; and (5) by providing a model for how the idea of equivalent protections might be addressed for research funded by Canadian agencies but conducted in other countries.

Hyperoxia and hypergravity are independent risk factors of atelectasis in healthy sitting humans: a pulmonary ultrasound and SPECT/CT study.

PubMed

Dussault, C; Gontier, E; Verret, C; Soret, M; Boussuges, A; Hedenstierna, G; Montmerle-Borgdorff, S

2016-07-01

Aeroatelectasis has developed in aircrew flying routine peacetime flights on the latest generation high-performance aircraft, when undergoing excessive oxygen supply. To single out the effects of hyperoxia and hypergravity on lung tissue compression, and on ventilation and perfusion, eight subjects were studied before and after 1 h 15 min exposure to +1 to +3.5 Gz in a human centrifuge. They performed the protocol three times, breathing air, 44.5% O2, or 100% O2 and underwent functional and topographical imaging of the whole lung by ultrasound and single-photon emission computed tomography combined with computed tomography (SPECT/CT). Ultrasound lung comets (ULC) and atelectasis both increased after exposure. The number of ULC was <1 pre protocol (i.e., normal lung) and larger post 100% O2 (22 ± 3, mean ± SD) than in all other conditions (P < 0.001). Post 44.5% O2 differed from air (P < 0.05). Seven subjects showed low- to medium-grade atelectasis post 100% O2 There was an effect on grade of gas mixture and hypergravity, with interaction (P < 0.001, respectively); 100% O2, 44.5% O2, and air differed from each other (P < 0.05). SPECT ventilation and perfusion were always normal. Ultrasound concurred with CT in showing normal lung in the upper third and ULC/atelectasis in posterior and inferior areas, not for other localizations. In conclusion, hyperoxia and hypergravity are independent risk factors of reversible atelectasis formation. Ultrasound is a useful screening tool. Together with electrical impedance tomography measurements (reported separately), these findings show that zones with decreased ventilation prone to transient airway closure are present above atelectatic areas. Copyright © 2016 the American Physiological Society.

Screening of missing proteins in the human liver proteome by improved MRM-approach-based targeted proteomics.

PubMed

Chen, Chen; Liu, Xiaohui; Zheng, Weimin; Zhang, Lei; Yao, Jun; Yang, Pengyuan

2014-04-04

To completely annotate the human genome, the task of identifying and characterizing proteins that currently lack mass spectrometry (MS) evidence is inevitable and urgent. In this study, as the first effort to screen missing proteins in large scale, we developed an approach based on SDS-PAGE followed by liquid chromatography-multiple reaction monitoring (LC-MRM), for screening of those missing proteins with only a single peptide hit in the previous liver proteome data set. Proteins extracted from normal human liver were separated in SDS-PAGE and digested in split gel slice, and the resulting digests were then subjected to LC-schedule MRM analysis. The MRM assays were developed through synthesized crude peptides for target peptides. In total, the expressions of 57 target proteins were confirmed from 185 MRM assays in normal human liver tissues. Among the proved 57 one-hit wonders, 50 proteins are of the minimally redundant set in the PeptideAtlas database, 7 proteins even have none MS-based information previously in various biological processes. We conclude that our SDS-PAGE-MRM workflow can be a powerful approach to screen missing or poorly characterized proteins in different samples and to provide their quantity if detected. The MRM raw data have been uploaded to ISB/SRM Atlas/PASSEL (PXD000648).

In the carotid body, galanin is a signal for neurogenesis in young, and for neurodegeneration in the old and in drug-addicted subjects

PubMed Central

Mazzatenta, Andrea; Marconi, Guya D.; Zara, Susi; Cataldi, Amelia; Porzionato, Andrea; Di Giulio, Camillo

2014-01-01

The carotid body is a highly specialized chemoreceptive structure for the detection of and reaction to hypoxia, through induction of an increase in hypoxia inducible factor. As tissue hypoxia increases with aging and can have dramatic effects in respiratory depression induced by drug addiction, we investigated the carotid body in young and old healthy subjects in comparison with drug-addicted subjects, including the expression of the neurotransmitter galanin. Galanin expression was recently reported for neuronal-like cells of the human carotid body, and it is implicated in several functions in neurons. In particular, this includes the regulation of differentiation of neural stem cells, and participation in the development and plasticity of the nervous system. Using immunohistochemistry detection, we demonstrate that galanin expression in the human carotid body in healthy older subjects and drug-addicted subjects is significantly reduced in comparison with healthy young subjects. This demonstrates not only the effects of normal aging and senescence, but also in the drug-addicted subjects, this appears to be due to a disorganization of the chemo-sensory region. With both aging and drug addiction, this results in a physiological reduction in neuronal-like cells, coupled with interlobular and intralobular increases in connective tissue fibers. Consequently, in both aging and drug addiction, this reduction of neuronal-like cells and the regeneration suggest that the carotid body is losing its sensory capabilities, with the transmission of chemoreceptive signals dramatically and vitally reduced. The level of galanin expression would thus provide a signal for neurogenesis in young subjects, and for neurodegeneration in older and drug-addicted subjects. PMID:25400591

Microvascular Endothelial Dysfunction in Sedentary, Obese Humans is mediated by NADPH Oxidase; Influence of Exercise Training

PubMed Central

La Favor, Justin D.; Dubis, Gabriel S.; Yan, Huimin; White, Joseph D.; Nelson, Margaret A.M.; Anderson, Ethan J.; Hickner, Robert C.

2016-01-01

Objective The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and to determine the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results Young, sedentary men and women were divided into lean (BMI 18–25; n=14), intermediate (BMI 28–32.5; n=13), and obese (BMI 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2O2) and superoxide levels in the vastus lateralis of obese compared to both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase (Nox) inhibitor, lowered (normalized) H2O2 and superoxide levels and reversed microvascular endothelial dysfunction in obese subjects. Following 8-weeks of exercise, H2O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the Nox subunits p22phox, p47phox, and p67phox were increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions This study implicates Nox as a source of excessive ROS production in skeletal muscle of obese individuals, and links excessive Nox derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladies. PMID:27765769

Safety assessment of 4-week oral intake of proanthocyanidin-rich grape seed extract in healthy subjects.

PubMed

Sano, Atsushi

2017-10-01

A clinical study was conducted to assess the safety and tolerability of oral doses of proanthocyanidin-rich grape seed extract (GSE) in healthy Japanese adult volunteers. In an open-label, 4-week toxicity test, 29 subjects daily received 1000, 1500, or 2500 mg GSE orally. Serum Fe levels of two subjects in the 2500 mg GSE group decreased to 61 and 60 μg/100 mL from 205 and 182 μg/100 mL at baseline respectively, at second week of GSE consumption; these values are low but within the normal range for the Japanese population. Two weeks after completing the 4-week course of GSE ingestion, the serum Fe levels of both subjects returned to near baseline levels (210 and 189 μg/100 mL). No subject discontinued the study. Oral intake of GSE up to 2500 mg for 4 weeks was found to be generally safe and well tolerated in humans. Research with a larger number of subjects is required to confirm these findings. Copyright © 2016. Published by Elsevier Ltd.

The perception of verticality in lunar and Martian gravity conditions.

PubMed

de Winkel, Ksander N; Clément, Gilles; Groen, Eric L; Werkhoven, Peter J

2012-10-31

Although the mechanisms of neural adaptation to weightlessness and re-adaptation to Earth-gravity have received a lot of attention since the first human space flight, there is as yet little knowledge about how spatial orientation is affected by partial gravity, such as lunar gravity of 0.16 g or Martian gravity of 0.38 g. Up to now twelve astronauts have spent a cumulated time of approximately 80 h on the lunar surface, but no psychophysical experiments were conducted to investigate their perception of verticality. We investigated how the subjective vertical (SV) was affected by reduced gravity levels during the first European Parabolic Flight Campaign of Partial Gravity. In normal and hypergravity, subjects accurately aligned their SV with the gravitational vertical. However, when gravity was below a certain threshold, subjects aligned their SV with their body longitudinal axis. The value of the threshold varied considerably between subjects, ranging from 0.03 to 0.57 g. Despite the small number of subjects, there was a significant positive correlation of the threshold with subject age, which calls for further investigation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Longitudinal Lung Function Decrease in Subjects with Spontaneous Healed Pulmonary Tuberculosis.

PubMed

Lee, Seung Heon; Kwon, Amy M; Yang, Hae-Chung; Lee, Seung Ku; Kim, Young; Choi, Jong Hyun; Kim, Je Hyeong; Shin, Chol

2016-01-01

We compared the longitudinal course of post-bronchodilator Forced Expiratory Volume in 1 second (pFEV1) over a 10-year period in subjects with spontaneous healed pulmonary tuberculosis (SHPTB) with that in normal subjects. We prospectively investigated 339 subjects with SHPTB and 3211 normal subjects. pFEV1 values measured biannually over 10 years were analyzed using mixed effects model. At baseline, there were no differences in gender, smoking amount, and mean height, except mean age (50.0 ± 8.1 VS. 48.1 ± 7.3, P< 0.001) between the SHPTB and normal group. 52% of the 339 participants with SHPTB and 56% of the 3211 normal participants participated till the end of study. According to the final model, the SHPTB group showed significantly larger decrease in the average pFEV1 over the time than the normal group (P< 0.001) adjusted for gender, age, height, smoking pack years, and time effects. Especially, the interaction effect between time and group was statistically significant (P = 0.036). The average lung function in terms of pFEV1 decreases faster in subjects with SHPTB than in normal individuals over time.

Allopurinol therapy and cataractogenesis in humans

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

Lerman, S.; Megaw, J.M.; Gardner, K.

1982-08-01

Long-term ingestion of allopurinol, an antihyperuricemic agent used to treat gout, may be related to the development of lens opacities in relatively young patients (second to fifth decades of life). Cataracts obtained from three patients taking allopurinol were subjected to high-resolution phosphorescence spectroscopy. The characteristic allopurinol triplet was demonstrated in all three cataracts. Identical spectra were obtained for normal human lenses incubated in media containing 10(-3)M allopurinol and exposed to 1.2 mW/cm2 ultraviolet radiation for 16 hours; control lenses (irradiated without allopurinol) showed no allopurinol triplets. Similar data were obtained for lenses from rats given one dose of allopurinol andmore » exposed to ultraviolet radiation overnight. These data provide evidence that allopurinol can be photobound in rat and human lenses and suggest its cataractogenic potential.« less

Apparent respiration rate of the human corneal epithelium with tetracaine HCl and benoxinate HCl.

PubMed

Bentley, C R; Larke, J R

1983-12-01

Local anesthetics may have a cytotoxic effect which causes a depression in the apparent epithelial oxygen uptake rate (AEOR) of the cornea. We measured the AEOR of human corneas in vivo before and after applying 1% tetracaine (amethocaine) HCl and 0.4% benoxinate HCl. These drugs had no effect on AEOR. In human corneas that had been subjected to a period of hypoxia, AEOR was slightly higher after administration of benoxinate, a result in the opposite direction to that expected on the grounds of toxicity. The increase was not statistically significant. We conclude that clinical doses of tetracaine HCl and benoxinate HCl normally have a minimal cytotoxic effect, and that this is similarly true when benoxinate is applied to the cornea after contact lens wear.

Measurement of Young's modulus in the in vivo human vocal folds.

PubMed

Tran, Q T; Berke, G S; Gerratt, B R; Kreiman, J

1993-08-01

Currently, surgeons have no objective means to evaluate and optimize results of phonosurgery intraoperatively. Instead, they usually judge the vocal folds subjectively by visual inspection or by listening to the voice. This paper describes a new device that measures Young's (elastic) modulus values for the human vocal fold intraoperatively. Physiologically, the modulus of the vocal fold may be important in determining the nature of vocal fold vibration in normal and pathologic states. This study also reports the effect of recurrent laryngeal nerve stimulation on Young's modulus of the human vocal folds, measured by means of transcutaneous nerve stimulation techniques. Young's modulus increased with increases in current stimulation to the recurrent laryngeal nerve. Ultimately, Young's modulus values may assist surgeons in optimizing the results of various phonosurgeries.

Modulation of high-frequency vestibuloocular reflex during visual tracking in humans

NASA Technical Reports Server (NTRS)

Das, V. E.; Leigh, R. J.; Thomas, C. W.; Averbuch-Heller, L.; Zivotofsky, A. Z.; Discenna, A. O.; Dell'Osso, L. F.

1995-01-01

1. Humans may visually track a moving object either when they are stationary or in motion. To investigate visual-vestibular interaction during both conditions, we compared horizontal smooth pursuit (SP) and active combined eye-head tracking (CEHT) of a target moving sinusoidally at 0.4 Hz in four normal subjects while the subjects were either stationary or vibrated in yaw at 2.8 Hz. We also measured the visually enhanced vestibuloocular reflex (VVOR) during vibration in yaw at 2.8 Hz over a peak head velocity range of 5-40 degrees/s. 2. We found that the gain of the VVOR at 2.8 Hz increased in all four subjects as peak head velocity increased (P < 0.001), with minimal phase changes, such that mean retinal image slip was held below 5 degrees/s. However, no corresponding modulation in vestibuloocular reflex gain occurred with increasing peak head velocity during a control condition when subjects were rotated in darkness. 3. During both horizontal SP and CEHT, tracking gains were similar, and the mean slip speed of the target's image on the retina was held below 5.5 degrees/s whether subjects were stationary or being vibrated at 2.8 Hz. During both horizontal SP and CEHT of target motion at 0.4 Hz, while subjects were vibrated in yaw, VVOR gain for the 2.8-Hz head rotations was similar to or higher than that achieved during fixation of a stationary target. This is in contrast to the decrease of VVOR gain that is reported while stationary subjects perform CEHT.(ABSTRACT TRUNCATED AT 250 WORDS).

Amount of HIV DNA in Peripheral Blood Mononuclear Cells is Proportional to the Severity of HIV-1-Associated Neurocognitive Disorders

PubMed Central

Shiramizu, Bruce; Williams, Andrew E.; Shikuma, Cecilia; Valcour, Victor

2009-01-01

Human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells was previously associated with neuropsychological function. By including individuals encompassing the full range of HIV-1-associated neurocognitive disorders, this study reports results from subjects with normal cognition, minor cognitive motor disorder, and HIV-1-associated dementia. Individuals with normal cognition had relatively low HIV DNA levels compared to those with minor cognitive motor disorder and HIV-1-associated dementia. Neuropsychological deficits were significantly associated with entry HIV DNA in all domains. These findings demonstrate for the first time that the severity of HIV-1-associated neurocognitive disorders is proportional to the amount of circulating HIV DNA. PMID:19359454

Phenformin-induced Hypoglycaemia in Normal Subjects*

PubMed Central

Lyngsøe, J.; Trap-Jensen, J.

1969-01-01

Study of the effect of phenformin on the blood glucose level in normal subjects before and during 70 hours of starvation showed a statistically significant hypoglycaemic effect after 40 hours of starvation. This effect was not due to increased glucose utilization. Another finding in this study was a statistically significant decrease in total urinary nitrogen excretion during starvation in subjects given phenformin. These findings show that the hypoglycaemic effect of phenformin in starved normal subjects is due to inhibition of gluconeogenesis. PMID:5780431

Abnormal lung sounds in patients with asthma during episodes with normal lung function.

PubMed

Schreur, H J; Vanderschoot, J; Zwinderman, A H; Dijkman, J H; Sterk, P J

1994-07-01

Even in patients with clinically stable asthma with normal lung function, the airways are characterized by inflammatory changes, including mucosal swelling. In order to investigate whether lung sounds can distinguish these subjects from normal subjects, we compared lung sound characteristics between eight normal and nine symptom-free subjects with mild asthma. All subjects underwent simultaneous recordings of airflow, lung volume changes, and lung sounds during standardized quiet breathing, and during forced maneuvers. Flow-dependent power spectra were computed using fast Fourier transform. For each spectrum we determined lung sound intensity (LSI), frequencies (Q25%, Q50%, Q75%) wheezing (W), and W%. The results were analyzed by ANOVA. During expiration, LSI was lower in patients with asthma than in healthy controls, in particular at relatively low airflow values. During quiet expiration, Q25% to Q75% were higher in asthmatics than in healthy controls, while the change of Q25% to Q75% with flow was greater in asthmatic than in normal subjects. The W and W% were not different between the subject groups. The results indicate that at given airflows, lung sounds are lower in intensity and higher in pitch in asthmatics as compared with controls. This suggests that the generation and/or transmission of lung sounds in symptom-free patients with stable asthma differ from that in normal subjects, even when lung function is within the normal range. Therefore, airflow standardized phonopneumography might reflect morphologic changes in airways of patients with asthma.

Enhanced anatomical calibration in human movement analysis.

PubMed

Donati, Marco; Camomilla, Valentina; Vannozzi, Giuseppe; Cappozzo, Aurelio

2007-07-01

The representation of human movement requires knowledge of both movement and morphology of bony segments. The determination of subject-specific morphology data and their registration with movement data is accomplished through an anatomical calibration procedure (calibrated anatomical systems technique: CAST). This paper describes a novel approach to this calibration (UP-CAST) which, as compared with normally used techniques, achieves better repeatability, a shorter application time, and can be effectively performed by non-skilled examiners. Instead of the manual location of prominent bony anatomical landmarks, the description of which is affected by subjective interpretation, a large number of unlabelled points is acquired over prominent parts of the subject's bone, using a wand fitted with markers. A digital model of a template-bone is then submitted to isomorphic deformation and re-orientation to optimally match the above-mentioned points. The locations of anatomical landmarks are automatically made available. The UP-CAST was validated considering the femur as a paradigmatic case. Intra- and inter-examiner repeatability of the identification of anatomical landmarks was assessed both in vivo, using average weight subjects, and on bare bones. Accuracy of the identification was assessed using the anatomical landmark locations manually located on bare bones as reference. The repeatability of this method was markedly higher than that reported in the literature and obtained using the conventional palpation (ranges: 0.9-7.6 mm and 13.4-17.9, respectively). Accuracy resulted, on average, in a maximal error of 11 mm. Results suggest that the principal source of variability resides in the discrepancy between subject's and template bone morphology and not in the inter-examiner differences. The UP-CAST anatomical calibration could be considered a promising alternative to conventional calibration contributing to a more repeatable 3D human movement analysis.

Sex and menopausal status influence human dietary requirements for the nutrient choline.

PubMed

Fischer, Leslie M; daCosta, Kerry Ann; Kwock, Lester; Stewart, Paul W; Lu, Tsui-Shan; Stabler, Sally P; Allen, Robert H; Zeisel, Steven H

2007-05-01

Although humans require dietary choline for methyl donation, membrane function, and neurotransmission, choline can also be derived from the de novo synthesis of phosphatidylcholine, which is up-regulated by estrogen. A recommended Adequate Intake (AI) exists for choline; however, an Estimated Average Requirement has not been set because of a lack of sufficient human data. The objective of the study was to evaluate the dietary requirements for choline in healthy men and women and to investigate the clinical sequelae of choline deficiency. Fifty-seven adult subjects (26 men, 16 premenopausal women, 15 postmenopausal women) were fed a diet containing 550 mg choline x 70 kg(-1) x d(-1) for 10 d followed by <50 mg choline x 70 kg(-1) x d(-1) with or without a folic acid supplement (400 microg/d per randomization) for up to 42 d. Subjects who developed organ dysfunction during this diet had normal organ function restored after incremental amounts of choline were added back to the diet. Blood and urine were monitored for signs of toxicity and metabolite concentrations, and liver fat was assessed by using magnetic resonance imaging. When deprived of dietary choline, 77% of men and 80% of postmenopausal women developed fatty liver or muscle damage, whereas only 44% of premenopausal women developed such signs of organ dysfunction. Moreover, 6 men developed these signs while consuming 550 mg choline x 70 kg(-1) x d(-1), the AI for choline. Folic acid supplementation did not alter the subjects' response. Subject characteristics (eg, menopausal status) modulated the dietary requirement for choline, and a daily intake at the current AI was not sufficient to prevent organ dysfunction in 19 of the subjects.

Long-Term Changes in Adiposity and Glycemic Control Are Associated With Past Adenovirus Infection

PubMed Central

Lin, Wan-Yu; Dubuisson, Olga; Rubicz, Rohina; Liu, Nianjun; Allison, David B.; Curran, Joanne E.; Comuzzie, Anthony G.; Blangero, John; Leach, Charles T.; Göring, Harald; Dhurandhar, Nikhil V.

2013-01-01

OBJECTIVE Ad36, a human adenovirus, increases adiposity but improves glycemic control in animal models. Similarly, natural Ad36 infection is cross-sectionally associated with greater adiposity and better glycemic control in humans. This study compared longitudinal observations in indices of adiposity (BMI and body fat percentage) and glycemic control (fasting glucose and insulin) in Ad36-infected versus uninfected adults. RESEARCH DESIGN AND METHODS Baseline sera from Hispanic men and women (n = 1,400) were screened post hoc for the presence of Ad36-specific antibodies. Indices of adiposity and glycemic control at baseline and at ∼10 years past the baseline were compared between seropositive and seronegative subjects, with adjustment for age and sex. In addition to age and sex, indices of glycemic control were adjusted for baseline BMI and were analyzed only for nondiabetic subjects. RESULTS Seropositive subjects (14.5%) had greater adiposity at baseline, compared with seronegative subjects. Longitudinally, seropositive subjects showed greater adiposity indices but lower fasting insulin levels. Subgroup analyses revealed that Ad36-seropositivity was associated with better baseline glycemic control and lower fasting insulin levels over time in the normal-weight group (BMI ≤25 kg/m2) and longitudinally, with greater adiposity in the overweight (BMI 25–30 kg/m2) and obese (BMI >30 kg/m2) men. Statistically, the differences between seropositive and seronegative individuals were modest in light of the multiple tests performed. CONCLUSIONS This study strengthens the plausibility that in humans, Ad36 increases adiposity and attenuates deterioration of glycemic control. Panoptically, the study raises the possibility that certain infections may modulate obesity or diabetes risk. A comprehensive understanding of these under-recognized factors is needed to effectively combat such metabolic disorders. PMID:23160725

Quantitative evaluation of human cerebellum-dependent motor learning through prism adaptation of hand-reaching movement.

PubMed

Hashimoto, Yuji; Honda, Takeru; Matsumura, Ken; Nakao, Makoto; Soga, Kazumasa; Katano, Kazuhiko; Yokota, Takanori; Mizusawa, Hidehiro; Nagao, Soichi; Ishikawa, Kinya

2015-01-01

The cerebellum plays important roles in motor coordination and learning. However, motor learning has not been quantitatively evaluated clinically. It thus remains unclear how motor learning is influenced by cerebellar diseases or aging, and is related with incoordination. Here, we present a new application for testing human cerebellum-dependent motor learning using prism adaptation. In our paradigm, the participant wearing prism-equipped goggles touches their index finger to the target presented on a touchscreen in every trial. The whole test consisted of three consecutive sessions: (1) 50 trials with normal vision (BASELINE), (2) 100 trials wearing the prism that shifts the visual field 25° rightward (PRISM), and (3) 50 trials without the prism (REMOVAL). In healthy subjects, the prism-induced finger-touch error, i.e., the distance between touch and target positions, was decreased gradually by motor learning through repetition of trials. We found that such motor learning could be quantified using the "adaptability index (AI)", which was calculated by multiplying each probability of [acquisition in the last 10 trials of PRISM], [retention in the initial five trials of REMOVAL], and [extinction in the last 10 trials of REMOVAL]. The AI of cerebellar patients less than 70 years old (mean, 0.227; n = 62) was lower than that of age-matched healthy subjects (0.867, n = 21; p < 0.0001). While AI did not correlate with the magnitude of dysmetria in ataxic patients, it declined in parallel with disease progression, suggesting a close correlation between the impaired cerebellar motor leaning and the dysmetria. Furthermore, AI decreased with aging in the healthy subjects over 70 years old compared with that in the healthy subjects less than 70 years old. We suggest that our paradigm of prism adaptation may allow us to quantitatively assess cerebellar motor learning in both normal and diseased conditions.

Probiotic supplementation prevents high-fat, overfeeding-induced insulin resistance in human subjects.

PubMed

Hulston, Carl J; Churnside, Amelia A; Venables, Michelle C

2015-02-28

The purpose of the present study was to determine whether probiotic supplementation (Lactobacillus casei Shirota (LcS)) prevents diet-induced insulin resistance in human subjects. A total of seventeen healthy subjects were randomised to either a probiotic (n 8) or a control (n 9) group. The probiotic group consumed a LcS-fermented milk drink twice daily for 4 weeks, whereas the control group received no supplementation. Subjects maintained their normal diet for the first 3 weeks of the study, after which they consumed a high-fat (65 % of energy), high-energy (50 % increase in energy intake) diet for 7 d. Whole-body insulin sensitivity was assessed by an oral glucose tolerance test conducted before and after overfeeding. Body mass increased by 0·6 (SE 0·2) kg in the control group (P< 0·05) and by 0·3 (SE 0·2) kg in the probiotic group (P>0·05). Fasting plasma glucose concentrations increased following 7 d of overeating (control group: 5·3 (SE 0·1) v. 5·6 (SE 0·2) mmol/l before and after overfeeding, respectively, P< 0·05), whereas fasting serum insulin concentrations were maintained in both groups. Glucose AUC values increased by 10 % (from 817 (SE 45) to 899 (SE 39) mmol/l per 120 min, P< 0·05) and whole-body insulin sensitivity decreased by 27 % (from 5·3 (SE 1·4) to 3·9 (SE 0·9), P< 0·05) in the control group, whereas normal insulin sensitivity was maintained in the probiotic group (4·4 (SE 0·8) and 4·5 (SE 0·9) before and after overeating, respectively (P>0·05). These results suggest that probiotic supplementation may be useful in the prevention of diet-induced metabolic diseases such as type 2 diabetes.

Quantitative Evaluation of Human Cerebellum-Dependent Motor Learning through Prism Adaptation of Hand-Reaching Movement

PubMed Central

Hashimoto, Yuji; Honda, Takeru; Matsumura, Ken; Nakao, Makoto; Soga, Kazumasa; Katano, Kazuhiko; Yokota, Takanori; Mizusawa, Hidehiro; Nagao, Soichi; Ishikawa, Kinya

2015-01-01

The cerebellum plays important roles in motor coordination and learning. However, motor learning has not been quantitatively evaluated clinically. It thus remains unclear how motor learning is influenced by cerebellar diseases or aging, and is related with incoordination. Here, we present a new application for testing human cerebellum-dependent motor learning using prism adaptation. In our paradigm, the participant wearing prism-equipped goggles touches their index finger to the target presented on a touchscreen in every trial. The whole test consisted of three consecutive sessions: (1) 50 trials with normal vision (BASELINE), (2) 100 trials wearing the prism that shifts the visual field 25° rightward (PRISM), and (3) 50 trials without the prism (REMOVAL). In healthy subjects, the prism-induced finger-touch error, i.e., the distance between touch and target positions, was decreased gradually by motor learning through repetition of trials. We found that such motor learning could be quantified using the “adaptability index (AI)”, which was calculated by multiplying each probability of [acquisition in the last 10 trials of PRISM], [retention in the initial five trials of REMOVAL], and [extinction in the last 10 trials of REMOVAL]. The AI of cerebellar patients less than 70 years old (mean, 0.227; n = 62) was lower than that of age-matched healthy subjects (0.867, n = 21; p < 0.0001). While AI did not correlate with the magnitude of dysmetria in ataxic patients, it declined in parallel with disease progression, suggesting a close correlation between the impaired cerebellar motor leaning and the dysmetria. Furthermore, AI decreased with aging in the healthy subjects over 70 years old compared with that in the healthy subjects less than 70 years old. We suggest that our paradigm of prism adaptation may allow us to quantitatively assess cerebellar motor learning in both normal and diseased conditions. PMID:25785588

Spatial nonuniformity of the resting CBF and BOLD responses to sevoflurane: in vivo study of normal human subjects with magnetic resonance imaging.

PubMed

Qiu, Maolin; Ramani, Ramachandran; Swetye, Michael; Constable, Robert Todd

2008-12-01

Pulsed arterial spin labeling magnetic resonance imaging (MRI) was performed to investigate the local coupling between resting regional cerebral blood flow (rCBF) and BOLD (blood oxygen level dependent) signal changes in 22 normal human subjects during the administration of 0.25 MAC (minimum alveolar concentration) sevoflurane. Two states were compared with subjects at rest: anesthesia and no-anesthesia. Regions of both significantly increased and decreased resting-state rCBF were observed. Increases were limited primarily to subcortical structures and insula, whereas, decreases were observed primarily in neocortical regions. No significant change was found in global CBF (gCBF). By simultaneously measuring rCBF and BOLD, region-specific anesthetic effects on the coupling between rCBF and BOLD were identified. Multiple comparisons of the agent-induced rCBF and BOLD changes demonstrated significant (P < 0.05) spatial variability in rCBF-BOLD coupling. The slope of the linear regression line for AC, where rCBF was increased by sevoflurane, was markedly smaller than the slope for those ROIs where rCBF was decreased by sevoflurane, indicating a bigger change in BOLD per unit change in rCBF in regions where rCBF was increased by sevoflurane. These results suggest that it would be inaccurate to use a global quantitative model to describe coupling across all brain regions and in all anesthesia conditions. The observed spatial nonuniformity of rCBF and BOLD signal changes suggests that any interpretation of BOLD fMRI data in the presence of an anesthetic requires consideration of these insights. Copyright 2007 Wiley-Liss, Inc.

Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

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

Bruzzone, Santina, E-mail: santina.bruzzone@unige.it; Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova; Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova

Highlights: Black-Right-Pointing-Pointer ABA is an endogenous hormone in humans, regulating different cell responses. Black-Right-Pointing-Pointer ABA reverts some of the functions altered in SSc fibroblasts to a normal phenotype. Black-Right-Pointing-Pointer UV-B irradiation increases ABA content in SSc cultures. Black-Right-Pointing-Pointer SSc fibroblasts could benefit from exposure to ABA and/or to UV-B. -- Abstract: The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated themore » effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-{beta} (TGF-{beta}). Conversely, migration toward ABA, but not toward TGF-{beta}, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.« less

A comparison of the effects of IGF-I and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers.

PubMed

Russell-Jones, D L; Bates, A T; Umpleby, A M; Hennessy, T R; Bowes, S B; Hopkins, K D; Jackson, N; Kelly, J; Shojaee-Moradie, F; Jones, R H

1995-06-01

The metabolic and cardiovascular effects of recombinant human IGF-I were compared to insulin in six normal subjects. Subjects were studied twice and intravenously received an infusion of [6,6-2H2]glucose (0-480 min) and in random order either IGF-I 20 micrograms kg-1 h-1 (43.7 pmol kg-1 min-1 or insulin 0.5 mU kg-1 min-1 (3.4 pmol kg-1 min-1) with an euglycaemic clamp. One subject was withdrawn following a serious adverse event. During the IGF-I infusion glucose appearance rate (Ra) decreased from 1.79 +/- 0.13 at baseline (150-180 min) to 0.35 +/- 0.26 mg kg-1 min-1 (P < 0.01) at 360 min, and glucose utilization rate (Rd) increased from 1.79 +/- 0.28 to 4.17 +/- 0.84 mg kg-1 min-1 (P < 0.01). There was no change in free fatty acids (FFA) and an increase (percentage change from pre-infusion mean) in cardiac output +l37.3% +/- 9% (P < 0.01), heart rate +13% +/- 2% (P < 0.01) and stroke volume +21% +/- 7% (P < 0.05). During the insulin infusion glucose Ra decreased from 1.89 +/- 0.13 to 0.34 +/- 0.33 mg kg-1 min-1 (P < 0.01) and FFA from 0.546 mmol l-1 to 0.198 mmol l-1 (P < 0.01), glucose Rd increased from 1.89 +/- 0.18 to 5.41 +/- 1.47 mg kg-1 min-1 (P < 0.01) and there were no significant changes in the cardiovascular variables.

A Wearable Magneto-Inertial System for Gait Analysis (H-Gait): Validation on Normal Weight and Overweight/Obese Young Healthy Adults

PubMed Central

Gastaldi, Laura; Rosso, Valeria; Knaflitz, Marco; Tadano, Shigeru

2017-01-01

Background: Wearable magneto-inertial sensors are being increasingly used to obtain human motion measurements out of the lab, although their performance in applications requiring high accuracy, such as gait analysis, are still a subject of debate. The aim of this work was to validate a gait analysis system (H-Gait) based on magneto-inertial sensors, both in normal weight (NW) and overweight/obese (OW) subjects. The validation is performed against a reference multichannel recording system (STEP32), providing direct measurements of gait timings (through foot-switches) and joint angles in the sagittal plane (through electrogoniometers). Methods: Twenty-two young male subjects were recruited for the study (12 NW, 10 OW). After positioning body-fixed sensors of both systems, each subject was asked to walk, at a self-selected speed, over a 14-m straight path for 12 trials. Gait signals were recorded, at the same time, with the two systems. Spatio-temporal parameters, ankle, knee, and hip joint kinematics were extracted analyzing an average of 89 ± 13 gait cycles from each lower limb. Intraclass correlation coefficient and Bland-Altmann plots were used to compare H-Gait and STEP32 measurements. Changes in gait parameters and joint kinematics of OW with respect NW were also evaluated. Results: The two systems were highly consistent for cadence, while a lower agreement was found for the other spatio-temporal parameters. Ankle and knee joint kinematics is overall comparable. Joint ROMs values were slightly lower for H-Gait with respect to STEP32 for the ankle (by 1.9° for NW, and 1.6° for OW) and for the knee (by 4.1° for NW, and 1.8° for OW). More evident differences were found for hip joint, with ROMs values higher for H-Gait (by 6.8° for NW, and 9.5° for OW). NW and OW showed significant differences considering STEP32 (p = 0.0004), but not H-Gait (p = 0.06). In particular, overweight/obese subjects showed a higher cadence (55.0 vs. 52.3 strides/min) and a lower hip ROM (23.0° vs. 27.3°) than normal weight subjects. Conclusions: The two systems can be considered interchangeable for what concerns joint kinematics, except for the hip, where discrepancies were evidenced. Differences between normal and overweight/obese subjects were statistically significant using STEP32. The same tendency was observed using H-Gait. PMID:29065485

Metabolic energy demand and optimal walking speed in post-polio subjects with lower limb afflictions.

PubMed

Ghosh, A K; Ganguli, S; Bose, K S

1982-12-01

The metabolic demand, using the relationship between speed and energy cost, and the optimal speed of walking, estimated by means of speed and energy cost per unit distance travelled, were studied in 16 post-polio subjects with lower limb affliction and 20 normal subjects with sedentary habits. It was observed that the post-polio subjects consumed higher energy than the normal persons at each walking speed between 0.28 and 1.26 m/s. The optimal speed of walking in post-polio subjects was lower than that of the normal persons and was associated with a higher energy demand per unit distance travelled. It was deduced that the post-polio subjects. not having used any assistive devices for a long time, have acquired severe degrees of disability which not only hindered their normal gait but also demanded extra energy from them.

Validating a behavioral economic approach to assess food demand: effects of body mass index, dietary restraint, and impulsivity.

PubMed

Reslan, Summar; Saules, Karen K; Greenwald, Mark K

2012-10-01

Behavioral economic theory is a useful framework for analyzing factors influencing choice, but the majority of human behavioral economic research has focused on drug choice. The behavioral economic choice paradigm may also be valuable for understanding food-maintained behavior. Our primary objective was two-fold: (1) Validate a human laboratory model of food-appetitive behavior, and (2) Assess the contribution of individual level factors that may differentially impact food choice behavior. Two studies were conducted. In Study 1, female subjects (N=17) participated in two consecutive food choice experimental sessions, whereas in Study 2, female subjects (N=21) participated in one concurrent food choice experimental session. During consecutive choice sessions (Study 1), demand for the more palatable food (i.e., high-sugar/high-fat) was more inelastic than the less palatable (i.e., low-sugar/low-fat) option. During concurrent choice sessions, demand for the more palatable food (i.e., high-sugar/high-fat) was more inelastic for restrained vs. unrestrained eaters, and for those who were overweight vs. normal weight. Demand for both palatable and less palatable choices was more elastic for high-impulsive vs. low-impulsive subjects. These findings suggest that the behavioral economic framework can be used successfully to develop a human laboratory model of food-appetitive behavior. Copyright © 2012 Elsevier Ltd. All rights reserved.

Robust automatic measurement of 3D scanned models for the human body fat estimation.

PubMed

Giachetti, Andrea; Lovato, Christian; Piscitelli, Francesco; Milanese, Chiara; Zancanaro, Carlo

2015-03-01

In this paper, we present an automatic tool for estimating geometrical parameters from 3-D human scans independent on pose and robustly against the topological noise. It is based on an automatic segmentation of body parts exploiting curve skeleton processing and ad hoc heuristics able to remove problems due to different acquisition poses and body types. The software is able to locate body trunk and limbs, detect their directions, and compute parameters like volumes, areas, girths, and lengths. Experimental results demonstrate that measurements provided by our system on 3-D body scans of normal and overweight subjects acquired in different poses are highly correlated with the body fat estimates obtained on the same subjects with dual-energy X-rays absorptiometry (DXA) scanning. In particular, maximal lengths and girths, not requiring precise localization of anatomical landmarks, demonstrate a good correlation (up to 96%) with the body fat and trunk fat. Regression models based on our automatic measurements can be used to predict body fat values reasonably well.

Age-related changes in human vestibulo-ocular reflexes: Sinusoidal rotation and caloric tests

NASA Technical Reports Server (NTRS)

Peterka, R. J.; Black, F. O.; Schoenhoff, M. B.

1989-01-01

The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR dynamics, and to identify the distributions of parameters which describe VOR responses to caloric and to sinusoidal rotational stimuli in a putatively normal population. Caloric test parameters showed no consistent trend with age. Rotation test parameters showed declining response amplitude and slightly less compensatory response phase with increasing age. The magnitudes of these changes were not large relative to the variability within the population. The age-related trends in VOR were not consistent with the anatomic changes in the periphery reported by others which showed an increasing rate of peripheral hair cell and nerve fiber loss in subjects over 55 years. The poor correlation between physiological and anatomical data suggest that adaptive mechanisms in the central nervous system are important in maintaining the VOR.

Antioxidant effects of gastrointestinal digested purple carrot extract on the human cells of colonic mucosa.

PubMed

Olejnik, Anna; Rychlik, Joanna; Kidoń, Marcin; Czapski, Janusz; Kowalska, Katarzyna; Juzwa, Wojciech; Olkowicz, Mariola; Dembczyński, Radosław; Moyer, Mary Pat

2016-01-01

Purple carrot (PC) is a potential dietary constituent, which represents a valuable source of antioxidants and can modulate the reactive oxygen species (ROS) level in the gastrointestinal tract. Antioxidant capacity of a PC extract subjected to digestion process simulated in the artificial alimentary tract, including the stomach, small intestine and colon, was analyzed in normal human cells of colon mucosa. Results indicated that the extract obtained upon passage through the gastrointestinal tract, which could come into contact with the colonic cells in situ, was less potent than the extract, which was not subjected to digestion process. Digested PC extract exhibited intracellular ROS-inhibitory capacity, with 1mg/mL showing the ROS clearance of 18.4%. A 20.7% reduction in oxidative DNA damage due to colon mucosa cells' treatment with digested PC extract was observed. These findings indicate that PC extract is capable of colonic cells' protection against the adverse effects of oxidative stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Galanin does not affect the growth hormone-releasing hormone-stimulated growth hormone secretion in patients with hyperthyroidism.

PubMed

Giustina, A; Bussi, A R; Legati, F; Bossoni, S; Licini, M; Schettino, M; Zuccato, F; Wehrenberg, W B

1992-12-01

Patients with hyperthyroidism have reduced spontaneous and stimulated growth hormone (GH) secretion. The aim of our study was to evaluate the effects of galanin, a novel neuropeptide which stimulates GH secretion in man, on the GH response to GHRH in patients with hyperthyroidism. Eight untreated hyperthyroid patients with Graves' disease (6F, 2M, aged 25-50 years) and six healthy volunteers (3F, 3M, aged 27-76 years) underwent from -10 to 30 min in random order: (i) porcine galanin, iv, 500 micrograms in 100 ml saline; or (ii) saline, iv, 100 ml. A bolus of human GHRH(1-29)NH2, 100 micrograms, was injected iv at 0 min. Hyperthyroid patients showed blunted GH peaks after GHRH+saline (10.2 +/- 2.5 micrograms/l) compared to normal subjects (20.7 +/- 4.8 micrograms/l, p < 0.05). GH peaks after GHRH+galanin were also significantly lower in hyperthyroid subjects (12.5 +/- 3 micrograms/l) compared to normal subjects (43.8 +/- 6 micrograms/l, p < 0.05). That galanin is not able to reverse the blunted GH response to GHRH in hyperthyroidism suggests that hyperthyroxinemia may either increase the somatostatin release by the hypothalamus or directly affect the pituitary GH secretory capacity.

Contribution of tibiofemoral joint contact to net loads at the knee in gait.

PubMed

Walter, Jonathan P; Korkmaz, Nuray; Fregly, Benjamin J; Pandy, Marcus G

2015-07-01

Inverse dynamics analysis is commonly used to estimate the net loads at a joint during human motion. Most lower-limb models of movement represent the knee as a simple hinge joint when calculating muscle forces. This approach is limited because it neglects the contributions from tibiofemoral joint contact forces and may therefore lead to errors in estimated muscle forces. The aim of this study was to quantify the contributions of tibiofemoral joint contact loads to the net knee loads calculated from inverse dynamics for multiple subjects and multiple gait patterns. Tibiofemoral joint contact loads were measured in four subjects with instrumented implants as each subject walked at their preferred speed (normal gait) and performed prescribed gait modifications designed to treat medial knee osteoarthritis. Tibiofemoral contact loads contributed substantially to the net knee extension and knee adduction moments in normal gait with mean values of 16% and 54%, respectively. These findings suggest that knee-contact kinematics and loads should be included in lower-limb models of movement for more accurate determination of muscle forces. The results of this study may be used to guide the development of more realistic lower-limb models that account for the effects of tibiofemoral joint contact at the knee. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Effect of chewing speed on energy expenditure in healthy subjects.

PubMed

Paphangkorakit, Jarin; Leelayuwat, Naruemon; Boonyawat, Nattawat; Parniangtong, Auddamar; Sripratoom, Jindamanee

2014-08-01

The aim of the study was to investigate the effect of rate of chewing on energy expenditure in human subjects. Fourteen healthy subjects (aged 18-24 years) within the normal range of BMI participated in a cross-over experiment consisting of two 6-min sessions of gum chewing, slow (∼60 cycles/min) and fast (∼120 cycles/min) chewing. The resting energy expenditure (REE) and during gum chewing was measured using a ventilated hood connected to a gas analyzer system. The normality of data was explored using the Shapiro-Wilk test. The energy expenditure rate during chewing and the energy expenditure per chewing cycle were compared between the two chewing speeds using Wilcoxon signed ranks tests. The energy expenditure per chewing cycle during slow chewing (median 1.4, range 5.2 cal; mean 2.1±1.6 cal) was significantly higher than that during fast chewing (median 0.9, range 2.2 cal; mean 1.0±0.7 cal) (p < 0.005). However, the energy expenditure rate was not significantly different between the two chewing speeds (p > 0.05). The results of this study suggest that chewing at a slower speed could increase the energy expenditure per cycle and might affect the total daily energy expenditure.

Language systems in normal and aphasic human subjects: functional imaging studies and inferences from animal studies.

PubMed

Wise, Richard J S

2003-01-01

The old neurological model of language, based on the writings of Broca, Wernicke and Lichtheim in the 19th century, is now undergoing major modifications. Observations on the anatomy and physiology of auditory processing in non-human primates are giving strong indicators as to how speech perception is organised in the human brain. In the light of this knowledge, functional activation studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are achieving a new level of precision in the investigation of language organisation in the human brain, in a manner not possible with observations on patients with aphasic stroke. Although the use of functional imaging to inform methods of improving aphasia rehabilitation remains underdeveloped, there are strong indicators that this methodology will provide the means to research a very imperfectly developed area of therapy.

Simulation of thalamic prosthetic vision: reading accuracy, speed, and acuity in sighted humans.

PubMed

Vurro, Milena; Crowell, Anne Marie; Pezaris, John S

2014-01-01

The psychophysics of reading with artificial sight has received increasing attention as visual prostheses are becoming a real possibility to restore useful function to the blind through the coarse, pseudo-pixelized vision they generate. Studies to date have focused on simulating retinal and cortical prostheses; here we extend that work to report on thalamic designs. This study examined the reading performance of normally sighted human subjects using a simulation of three thalamic visual prostheses that varied in phosphene count, to help understand the level of functional ability afforded by thalamic designs in a task of daily living. Reading accuracy, reading speed, and reading acuity of 20 subjects were measured as a function of letter size, using a task based on the MNREAD chart. Results showed that fluid reading was feasible with appropriate combinations of letter size and phosphene count, and performance degraded smoothly as font size was decreased, with an approximate doubling of phosphene count resulting in an increase of 0.2 logMAR in acuity. Results here were consistent with previous results from our laboratory. Results were also consistent with those from the literature, despite using naive subjects who were not trained on the simulator, in contrast to other reports.

Human postural responses to motion of real and virtual visual environments under different support base conditions.

PubMed

Mergner, T; Schweigart, G; Maurer, C; Blümle, A

2005-12-01

The role of visual orientation cues for human control of upright stance is still not well understood. We, therefore, investigated stance control during motion of a visual scene as stimulus, varying the stimulus parameters and the contribution from other senses (vestibular and leg proprioceptive cues present or absent). Eight normal subjects and three patients with chronic bilateral loss of vestibular function participated. They stood on a motion platform inside a cabin with an optokinetic pattern on its interior walls. The cabin was sinusoidally rotated in anterior-posterior (a-p) direction with the horizontal rotation axis through the ankle joints (f=0.05-0.4 Hz; A (max)=0.25 degrees -4 degrees ; v (max)=0.08-10 degrees /s). The subjects' centre of mass (COM) angular position was calculated from opto-electronically measured body sway parameters. The platform was either kept stationary or moved by coupling its position 1:1 to a-p hip position ('body sway referenced', BSR, platform condition), by which proprioceptive feedback of ankle joint angle became inactivated. The visual stimulus evoked in-phase COM excursions (visual responses) in all subjects. (1) In normal subjects on a stationary platform, the visual responses showed saturation with both increasing velocity and displacement of the visual stimulus. The saturation showed up abruptly when visually evoked COM velocity and displacement reached approximately 0.1 degrees /s and 0.1 degrees , respectively. (2) In normal subjects on a BSR platform (proprioceptive feedback disabled), the visual responses showed similar saturation characteristics, but at clearly higher COM velocity and displacement values ( approximately 1 degrees /s and 1 degrees , respectively). (3) In patients on a stationary platform (no vestibular cues), the visual responses were basically similar to those of the normal subjects, apart from somewhat higher gain values and less-pronounced saturation effects. (4) In patients on a BSR platform (no vestibular and proprioceptive cues, presumably only somatosensory graviceptive and visual cues), the visual responses showed an abnormal increase in gain with increasing stimulus frequency in addition to a displacement saturation. On the normal subjects we performed additional experiments in which we varied the gain of the visual response by using a 'virtual reality' visual stimulus or by applying small lateral platform tilts. This did not affect the saturation characteristics of the visual response to a considerable degree. We compared the present results to previous psychophysical findings on motion perception, noting similarities of the saturation characteristics in (1) with leg proprioceptive detection thresholds of approximately 0.1 degrees /s and 0.1 degrees and those in (2) with vestibular detection thresholds of 1 degrees /s and 1 degrees , respectively. From the psychophysical data one might hypothesise that a proprioceptive postural mechanism limits the visually evoked body excursions if these excursions exceed 0.1 degrees /s and 0.1 degrees in condition (1) and that a vestibular mechanism is doing so at 1 degrees /s and 1 degrees in (2). To better understand this, we performed computer simulations using a posture control model with multiple sensory feedbacks. We had recently designed the model to describe postural responses to body pull and platform tilt stimuli. Here, we added a visual input and adjusted its gain to fit the simulated data to the experimental data. The saturation characteristics of the visual responses of the normals were well mimicked by the simulations. They were caused by central thresholds of proprioceptive, vestibular and somatosensory signals in the model, which, however, differed from the psychophysical thresholds. Yet, we demonstrate in a theoretical approach that for condition (1) the model can be made monomodal proprioceptive with the psychophysical 0.1 degrees /s and 0.1 degrees thresholds, and for (2) monomodal vestibular with the psychophysical 1 degrees /s and 1 degrees thresholds, and still shows the corresponding saturation characteristics (whereas our original model covers both conditions without adjustments). The model simulations also predicted the almost normal visual responses of patients on a stationary platform and their clearly abnormal responses on a BSR platform.

On the other hand: including left-handers in cognitive neuroscience and neurogenetics.

PubMed

Willems, Roel M; Van der Haegen, Lise; Fisher, Simon E; Francks, Clyde

2014-03-01

Left-handers are often excluded from study cohorts in neuroscience and neurogenetics in order to reduce variance in the data. However, recent investigations have shown that the inclusion or targeted recruitment of left-handers can be informative in studies on a range of topics, such as cerebral lateralization and the genetic underpinning of asymmetrical brain development. Left-handed individuals represent a substantial portion of the human population and therefore left-handedness falls within the normal range of human diversity; thus, it is important to account for this variation in our understanding of brain functioning. We call for neuroscientists and neurogeneticists to recognize the potential of studying this often-discarded group of research subjects.

Quantifying Human Performance of a Dynamic Military Target Detection Task: An Application of the Theory of Signal Detection.

DTIC Science & Technology

1995-06-01

applied to analyze numerous experimental tasks (Macmillan and Creelman , 1991). One of these tasks, target detection, is the subject research. In...between each associated pair of false alarm rate and hit rate z-scores is d’ for the bias level associated with the pairing (Macmillan and Creelman , 1991...unequal variance in normal distributions (Macmillan and Creelman , 1991). 61 1966). It is described in detail for the interested reader by Green and

Pulse Wave Velocity as Marker of Preclinical Arterial Disease: Reference Levels in a Uruguayan Population Considering Wave Detection Algorithms, Path Lengths, Aging, and Blood Pressure

PubMed Central

Farro, Ignacio; Bia, Daniel; Zócalo, Yanina; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Alallón, Walter; Lluberas, Ricardo; Armentano, Ricardo L.

2012-01-01

Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n = 429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the “reference population”; the group of subjects with optimal/normal blood pressures levels at study time represented the “normal population.” Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes. PMID:22666551

Rapamycin Inhibits Human Laryngotracheal Stenosis–derived Fibroblast Proliferation, Metabolism, and Function in Vitro

PubMed Central

Namba, Daryan R.; Ma, Garret; Samad, Idris; Ding, Dacheng; Pandian, Vinciya; Powell, Jonathan D.; Horton, Maureen R.; Hillel, Alexander T.

2015-01-01

Objective To determine if rapamycin inhibits the growth, function, and metabolism of human laryngotracheal stenosis (LTS)–derived fibroblasts. Study Design Controlled in vitro study. Setting Tertiary care hospital in a research university. Subjects and Methods Fibroblasts isolated from biopsies of 5 patients with laryngotracheal stenosis were cultured. Cell proliferation, histology, gene expression, and cellular metabolism of LTS-derived fibroblasts were assessed in 4 conditions: (1) fibroblast growth medium, (2) fibroblast growth medium with dimethylsulfoxide (DMSO), (3) fibroblast growth medium with 10−10 M (low-dose) rapamycin dissolved in DMSO, and (4) fibroblast growth medium with 10−9 M (high-dose) rapamycin dissolved in DMSO. Results The LTS fibroblast count and DNA concentration were reduced after treatment with high-dose rapamycin compared to DMSO (P = .0007) and normal (P = .0007) controls. Collagen I expression decreased after treatment with high-dose rapamycin versus control (P = .0051) and DMSO (P = .0093) controls. Maximal respiration decreased to 68.6 pMoles of oxygen/min/10 mg/protein from 96.9 for DMSO (P = .0002) and 97.0 for normal (P = .0022) controls. Adenosine triphosphate (ATP) production decreased to 66.8 pMoles from 88.1 for DMSO (P = .0006) and 83.3 for normal (P = .0003) controls. Basal respiration decreased to 78.6 pMoles from 108 for DMSO (P = .0002) and 101 for normal (P = .0014) controls. Conclusions Rapamycin demonstrated an anti-fibroblast effect by significantly reducing the proliferation, metabolism, and collagen deposition of human LTS fibroblast in vitro. Rapamycin significantly decreased oxidative phosphorylation of LTS fibroblasts, suggesting at a potential mechanism for the reduced proliferation and differentiation. Furthermore, rapamycin’s anti-fibroblast effects indicate a promising adjuvant therapy for the treatment of laryngotracheal stenosis. PMID:25754184

Human brain cancer studied by resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-Hui; Sun, Yi; Pu, Yang; Boydston-White, Susie; Liu, Yulong; Alfano, Robert R.

2012-11-01

The resonance Raman (RR) spectra of six types of human brain tissues are examined using a confocal micro-Raman system with 532-nm excitation in vitro. Forty-three RR spectra from seven subjects are investigated. The spectral peaks from malignant meningioma, stage III (cancer), benign meningioma (benign), normal meningeal tissues (normal), glioblastoma multiforme grade IV (cancer), acoustic neuroma (benign), and pituitary adenoma (benign) are analyzed. Using a 532-nm excitation, the resonance-enhanced peak at 1548 cm-1 (amide II) is observed in all of the tissue specimens, but is not observed in the spectra collected using the nonresonance Raman system. An increase in the intensity ratio of 1587 to 1605 cm-1 is observed in the RR spectra collected from meningeal cancer tissue as compared with the spectra collected from the benign and normal meningeal tissue. The peak around 1732 cm-1 attributed to fatty acids (lipids) are diminished in the spectra collected from the meningeal cancer tumors as compared with the spectra from normal and benign tissues. The characteristic band of spectral peaks observed between 2800 and 3100 cm-1 are attributed to the vibrations of methyl (-CH3) and methylene (-CH2-) groups. The ratio of the intensities of the spectral peaks of 2935 to 2880 cm-1 from the meningeal cancer tissues is found to be lower in comparison with that of the spectral peaks from normal, and benign tissues, which may be used as a distinct marker for distinguishing cancerous tissues from normal meningeal tissues. The statistical methods of principal component analysis and the support vector machine are used to analyze the RR spectral data collected from meningeal tissues, yielding a diagnostic sensitivity of 90.9% and specificity of 100% when two principal components are used.

Ventilation-perfusion distribution in normal subjects.

PubMed

Beck, Kenneth C; Johnson, Bruce D; Olson, Thomas P; Wilson, Theodore A

2012-09-01

Functional values of LogSD of the ventilation distribution (σ(V)) have been reported previously, but functional values of LogSD of the perfusion distribution (σ(q)) and the coefficient of correlation between ventilation and perfusion (ρ) have not been measured in humans. Here, we report values for σ(V), σ(q), and ρ obtained from wash-in data for three gases, helium and two soluble gases, acetylene and dimethyl ether. Normal subjects inspired gas containing the test gases, and the concentrations of the gases at end-expiration during the first 10 breaths were measured with the subjects at rest and at increasing levels of exercise. The regional distribution of ventilation and perfusion was described by a bivariate log-normal distribution with parameters σ(V), σ(q), and ρ, and these parameters were evaluated by matching the values of expired gas concentrations calculated for this distribution to the measured values. Values of cardiac output and LogSD ventilation/perfusion (Va/Q) were obtained. At rest, σ(q) is high (1.08 ± 0.12). With the onset of ventilation, σ(q) decreases to 0.85 ± 0.09 but remains higher than σ(V) (0.43 ± 0.09) at all exercise levels. Rho increases to 0.87 ± 0.07, and the value of LogSD Va/Q for light and moderate exercise is primarily the result of the difference between the magnitudes of σ(q) and σ(V). With known values for the parameters, the bivariate distribution describes the comprehensive distribution of ventilation and perfusion that underlies the distribution of the Va/Q ratio.

A new breakfast cereal containing guar gum reduces postprandial plasma glucose and insulin concentrations in normal-weight human subjects.

PubMed

Fairchild, R M; Ellis, P R; Byrne, A J; Luzio, S D; Mir, M A

1996-07-01

A new guar-containing wheatflake product was developed to assess its effect on carbohydrate tolerance in normal-weight, healthy subjects. The extruded wheatflake breakfast cereals containing 0 (control) or approximately 90 g guar gum/kg DM were fed to ten fasting, normal-weight, healthy subjects using a repeated measures design. The meals were similar in energy (approximately 1.8 MJ), available carbohydrate (78 g), protein (15 g) and fat (5.4 g) content. The guar gum content of the test meals was 6.3 g. Venous blood samples were taken fasting and at 15, 30, 45, 60, 90, 120, 150 and 240 min after commencing each breakfast and analysed for plasma glucose, insulin and C-peptide. The guar wheatflake meal produced a significant main effect for glucose and insulin at 0-60 min and 0-240 min time intervals respectively, but not for the C-peptide levels compared with the control meal. Significant reductions in postprandial glucose and insulin responses were seen following the guar wheatflake meal compared with the control meal at 15 and 60 min (glucose) and 15, 60, 90 and 120 min (insulin). The 60 and 120 min areas under the curve for glucose and insulin were significantly reduced by the guar gum meal, as was the 240 min area under the curve for insulin. Thus, it can be concluded that the use of a severe method of heat extrusion to produce guar wheatflakes does not diminish the physiological activity of the guar gum.

Physiological impact of patent foramen ovale on pulmonary gas exchange, ventilatory acclimatization, and thermoregulation.

PubMed

Lovering, Andrew T; Elliott, Jonathan E; Davis, James T

2016-08-01

The foramen ovale, which is part of the normal fetal cardiopulmonary circulation, fails to close after birth in ∼35% of the population and represents a potential source of right-to-left shunt. Despite the prevalence of patent foramen ovale (PFO) in the general population, cardiopulmonary, exercise, thermoregulatory, and altitude physiologists may have underestimated the potential effect of this shunted blood flow on normal physiological processes in otherwise healthy humans. Because this shunted blood bypasses the respiratory system, it would not participate in either gas exchange or respiratory system cooling and may have impacts on other physiological processes that remain undetermined. The consequences of this shunted blood flow in PFO-positive (PFO+) subjects can potentially have a significant, and negative, impact on the alveolar-to-arterial oxygen difference (AaDO2), ventilatory acclimatization to high altitude and respiratory system cooling with PFO+ subjects having a wider AaDO2 at rest, during exercise after acclimatization, blunted ventilatory acclimatization, and a higher core body temperature (∼0.4(°)C) at rest and during exercise. There is also an association of PFO with high-altitude pulmonary edema and acute mountain sickness. These effects on physiological processes are likely dependent on both the presence and size of the PFO, with small PFOs not likely to have significant/measureable effects. The PFO can be an important determinant of normal physiological processes and should be considered a potential confounder to the interpretation of former and future data, particularly in small data sets where a significant number of PFO+ subjects could be present and significantly impact the measured outcomes.

Total Antioxidant Status in Type 2 Diabetic Patients in Palestine.

PubMed

Kharroubi, Akram T; Darwish, Hisham M; Akkawi, Mutaz A; Ashareef, Abdelkareem A; Almasri, Zaher A; Bader, Khaldoun A; Khammash, Umaiyeh M

2015-01-01

The objective of this study was to compare the level of total antioxidant status (TAS) in type 2 diabetic and normal Palestinian subjects as well as the major factors influencing TAS levels. A sample of convenience composed of 212 type 2 diabetic and 208 normal subjects above the age of 40 were recruited. Only 9.8% of the subjects had normal body mass index (BMI) levels (<25), 29% were overweight (≥25 to <30), and 61.2% were obese (≥30). The mean levels of TAS were significantly higher in diabetic compared to control subjects (2.18 versus 1.84 mM Trolox, P = 0.001) and in hypertensive subjects compared to subjects with normal blood pressure (BP). Mean TAS levels were higher in obese compared to nonobese subjects (2.12 versus 1.85 mM Trolox, P = 0.001). Mean TAS levels were similarly higher in subjects with high fasting plasma glucose (FPG) compared to normal FPG (2.19 versus 1.90 mM Trolox) and high HbA1c (≥6.5%) compared to HbA1c < 6.5% (2.14 versus 1.91 mM Trolox). Multivariate analysis revealed that only diabetic status (P = 0.032) and the level of education (P = 0.036) were significantly associated with TAS. In conclusion diabetic patients had 18.5% increase in TAS levels compared to control subjects.

Pulmonary performance of elderly normal subjects and subjects with chronic obstructive pulmonary disease exposed to 0. 3 ppm nitrogen dioxide

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

Morrow, P.E.; Utell, M.J.; Bauer, M.A.

1992-02-01

Symptoms and changes in pulmonary function of subjects with chronic obstructive pulmonary disease (COPD) and elderly normal subjects, induced by a 4-h exposure to 0.3 ppm NO2, were investigated using a double-blind, crossover design with purified air. The 5-day experimental protocol required approximately 2 wk with at least a 5-day separation between randomized 4-h exposures to either NO2 or air which included several periods of exercise. Over a 2-yr period, COPD subjects, all with a history of smoking, consisting of 13 men and 7 women (mean age of 60.0 yr) and 20 elderly normal subjects of comparable age and sexmore » were evaluated. During intermittent light exercise, COPD subjects demonstrated progressive decrements in FVC and FEV1 compared with baseline with 0.3 ppm NO2, but not with air. Differences in percent changes from baseline data (air-NO2) showed an equivocal reduction in FVC by repeated measures of analysis of variance and cross-over t tests (p less than 0.10). Subgroup analyses suggested that responsiveness to NO2 decreased with severity of COPD; in elderly normal subjects, NO2-induced reduction in FEV1 was greater among smokers than never-smokers. A comparison of COPD and elderly normal subjects also revealed distinctions in NO2-induced responsiveness.« less

Objective evaluation of the visual acuity in human eyes

NASA Astrophysics Data System (ADS)

Rosales, M. A.; López-Olazagasti, E.; Ramírez-Zavaleta, G.; Varillas, G.; Tepichín, E.

2009-08-01

Traditionally, the quality of the human vision is evaluated by a subjective test in which the examiner asks the patient to read a series of characters of different sizes, located at a certain distance of the patient. Typically, we need to ensure a subtended angle of vision of 5 minutes, which implies an object of 8.8 mm high located at 6 meters (normal or 20/20 visual acuity). These characters constitute what is known as the Snellen chart, universally used to evaluate the spatial resolution of the human eyes. The mentioned process of identification of characters is carried out by means of the eye - brain system, giving an evaluation of the subjective visual performance. In this work we consider the eye as an isolated image-forming system, and show that it is possible to isolate the function of the eye from that of the brain in this process. By knowing the impulse response of the eye´s system we can obtain, in advance, the image of the Snellen chart simultaneously. From this information, we obtain the objective performance of the eye as the optical system under test. This type of results might help to detect anomalous situations of the human vision, like the so called "cerebral myopia".

Retinal pulse wave velocity measurement using spectral-domain optical coherence tomography.

PubMed

Li, Qian; Li, Lin; Fan, Shanhui; Dai, Cuixia; Chai, Xinyu; Zhou, Chuanqing

2018-02-01

The human eyes provide a natural window for noninvasive measurement of the pulse wave velocity (PWV) of small arteries. By measuring the retinal PWV, the stiffness of small arteries can be assessed, which may better detect early vascular diseases. Therefore, retinal PWV measurement has attracted increasing attention. In this study, a jump-scanning method was proposed for noninvasive measurement of retinal PWV using spectral-domain optical coherence tomography (SD-OCT). The jump-scanning method uses the phase-resolved Doppler OCT to obtain the pulse shapes. To realize PWV measurement, the jump-scanning method extracts the transit time of the pulse wave from an original OCT scanning site to another through a transient jump. The measured retinal arterial PWV of a young human subject with normal blood pressure was in the order of 20 to 30 mm/s, which was consistent with previous studies. As a comparison, PWV of 50 mm/s was measured for a young human subject with prehypertension, which was in accordance with the finding of strong association between retinal PWV and blood pressure. In summary, it is believed the proposed jump-scanning method could benefit the research and diagnosis of vascular diseases through the window of human eyes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hydroquinone induces DNA hypomethylation-independent overexpression of retroelements in human leukemia and hematopoietic stem cells.

PubMed

Conti, Anastasia; Rota, Federica; Ragni, Enrico; Favero, Chiara; Motta, Valeria; Lazzari, Lorenza; Bollati, Valentina; Fustinoni, Silvia; Dieci, Giorgio

2016-06-10

Hydroquinone (HQ) is an important benzene-derived metabolite associated with acute myelogenous leukemia risk. Although altered DNA methylation has been reported in both benzene-exposed human subjects and HQ-exposed cultured cells, the inventory of benzene metabolite effects on the epigenome is only starting to be established. In this study, we used a monocytic leukemia cell line (THP-1) and hematopoietic stem cells (HSCs) from cord blood to investigate the effects of HQ treatment on the expression of the three most important families of retrotransposons in the human genome: LINE-1, Alu and Endogenous retroviruses (HERVs), that are normally subjected to tight epigenetic silencing. We found a clear tendency towards increased retrotransposon expression in response to HQ exposure, more pronounced in the case of LINE-1 and HERV. Such a partial loss of silencing, however, was generally not associated with HQ-induced DNA hypomethylation. On the other hand, retroelement derepression was also observed in the same cells in response to the hypomethylating agent decitabine. These observations suggest the existence of different types of epigenetic switches operating at human retroelements, and point to retroelement activation in response to benzene-derived metabolites as a novel factor deserving attention in benzene carcinogenesis studies. Copyright © 2016 Elsevier Inc. All rights reserved.

[Change in the activity of natural killer cells in normal subjects and in virus diseases on exposure to interferon in vitro].

PubMed

Petrov, R V; Saidov, M Z; Koval'chuk, L V; Sorokin, A M; Kaganov, B S

1984-04-01

The activity of natural killers was examined in peripheral blood of healthy subjects and patients with chronic hepatitis and disseminated sclerosis. An attempt was made to correct natural killer activity by human leukocyte interferon in vitro. To assess the activity of natural killers, use was made of the method of serial dilutions. An optimal effector/target ratio was employed in experiments. The patients with chronic hepatitis and disseminated sclerosis demonstrated a reduction in the activity of natural killers whatever the effector/target ratio. The action of interferon in vitro is specific immunomodulatory in nature. Administration of interferon in a dose of 250 Units/ml raises the magnitude of the cytotoxic index in healthy donors and in patients with chronic hepatitis and disseminated sclerosis, making the shape of the killer activity curve approach that of normal. Such an approach can be used for preliminary assessment of the sensitivity of natural killers to interferon in viral diseases of man. The potentialities and efficacy of interferon in clinical medicine are discussed.

Quantifying interictal metabolic activity in human temporal lobe epilepsy

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

Henry, T.R.; Mazziotta, J.C.; Engel, J. Jr.

1990-09-01

The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on (18F)fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a singlemore » investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.« less

Sensitivity of estimated muscle force in forward simulation of normal walking

PubMed Central

Xiao, Ming; Higginson, Jill

2009-01-01

Generic muscle parameters are often used in muscle-driven simulations of human movement estimate individual muscle forces and function. The results may not be valid since muscle properties vary from subject to subject. This study investigated the effect of using generic parameters in a muscle-driven forward simulation on muscle force estimation. We generated a normal walking simulation in OpenSim and examined the sensitivity of individual muscle to perturbations in muscle parameters, including the number of muscles, maximum isometric force, optimal fiber length and tendon slack length. We found that when changing the number muscles included in the model, only magnitude of the estimated muscle forces was affected. Our results also suggest it is especially important to use accurate values of tendon slack length and optimal fiber length for ankle plantarflexors and knee extensors. Changes in force production one muscle were typically compensated for by changes in force production by muscles in the same functional muscle group, or the antagonistic muscle group. Conclusions regarding muscle function based on simulations with generic musculoskeletal parameters should be interpreted with caution. PMID:20498485

Plasma trypsin in chronic pancreatitis and pancreatic adenocarcinoma.

PubMed

Adrian, T E; Besterman, H S; Mallinson, C N; Pera, A; Redshaw, M R; Wood, T P; Bloom, S R

1979-10-01

We have used a simple and precise radioimmunoassay to measure trypsin in human plasma. Fasting plasma trypsin concentrations were extremely low in patients with chronic pancreatitis with steatorrhoea (5 +/- 2 ng/ml) when compared to healthy controls (86 +/- 7 ng/ml, p less than 0.001). In patients with chronic pancreatitis but no steatorrhoea basal plasma trypsin levels were similar to those of the normal controls (99 +/- 25 ng/ml). A small but significant postprandial rise in plasma trypsin concentrations was observed in normal subjects (mean increment 15 +/- 4%, p less than 0.005, paired t test) but was absent in patients with chronic pancreatitis with steatorrhoea. In contrast to exocrine deficient chronic pancreatitis, other malabsorptive conditions associated with steatorrhoea (active coeliac disease and acute tropical sprue) demonstrated mean fasting trypsin concentrations similar to controls. Patients with adenocarcinoma of the pancreas had basal trypsin concentrations similar to healthy subjects as did patients with adenocarcinoma of the stomach, colon, rectum, brochus, and breast. In some cases measurement of plasma trypsin may be of help in the differential diagnosis of steatorrhoea.

Uricosuric effect of Roselle (Hibiscus sabdariffa) in normal and renal-stone former subjects.

PubMed

Prasongwatana, Vitoon; Woottisin, Surachet; Sriboonlue, Pote; Kukongviriyapan, Veerapol

2008-05-22

The Roselle (Hibiscus sabdariffa) was investigated for its uricosuric effect. A human model with nine subjects with no history of renal stones (non-renal stone, NS) and nine with a history of renal stones (RS) was used in this study. A cup of tea made from 1.5 g of dry Roselle calyces was provided to subjects twice daily (morning and evening) for 15 days. A clotted blood and two consecutive 24-h urine samples were collected from each subject three times: (1) at baseline (control); (2) on days 14 and 15 during the tea drinking period; and (3) 15 days after the tea drinking was stopped (washout). Serum and 24-h urinary samples were analyzed for uric acid and other chemical compositions related to urinary stone risk factors. All analyzed serum parameters were within normal ranges and similar; between the two groups of subjects and among the three periods. Vis-à-vis the urinary parameters, most of the baseline values for both groups were similar. After taking the tea, the trend was an increase in oxalate and citrate in both groups and uric acid excretion and clearance in the NS group. In the RS group, both uric acid excretion and clearance were significantly increased (p<0.01). When the fractional excretion of uric acid (FEUa) was calculated, the values were clearly increased in both the NS and SF groups after the intake of tea and returned to baseline values in the washout period. These changes were more clearly observed when the data for each subject was presented individually. Our data demonstrate a uricosuric effect of Roselle calyces. Since the various chemical constituents in Roselle calyces have been identified, the one(s) exerting this uricosuric effect need to be identified.

Muscle force modification strategies are not consistent for gait retraining to reduce the knee adduction moment in individuals with knee osteoarthritis.

PubMed

Shull, Peter B; Huang, Yangjian; Schlotman, Taylor; Reinbolt, Jeffrey A

2015-09-18

While gait retraining paradigms that alter knee loads typically focus on modifying kinematics, the underlying muscle force modifications responsible for these kinematic changes remain largely unknown. As humans are generally thought to select uniform gait muscle patterns such as strategies based on fatigue cost functions or energy minimization, we hypothesized that a kinematic gait change known to reduce the knee adduction moment (i.e. toe-in gait) would be accompanied by a uniform muscle force modification strategy for individuals with symptomatic knee osteoarthritis. Ten subjects with self-reported knee pain and radiographic evidence of medial compartment knee osteoarthritis performed normal gait and toe-in gait modification walking trials. Two hundred muscle-actuated dynamic simulations (10 steps for normal gait and 10 steps from toe-in gait for each subject) were performed to determine muscle forces for each gait. Results showed that subjects internally rotated their feet during toe-in gait, which decreased the foot progression angle by 7° (p<0.01) and reduced the first peak knee adduction moment by 20% (p<0.01). While significant muscle force modifications were evidenced within individuals, there were no consistent muscle force modifications across all subjects. It may be that self-selected muscle pattern changes are not uniform for gait modification particularly for individuals with knee pain. Future studies focused on altering knee loads should not assume consistent muscle force modifications for a given kinematic gait change across subjects and should consider muscle forces in addition to kinematics in gait retraining paradigms. Copyright © 2015 Elsevier Ltd. All rights reserved.

A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa

PubMed Central

Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

2015-01-01

Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (Isc). Subsequent Isc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. Isc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704

A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

PubMed

Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

2015-03-01

Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.

Circadian rhythms in healthy aging--effects downstream from the pacemaker

NASA Technical Reports Server (NTRS)

Monk, T. H.; Kupfer, D. J.

2000-01-01

Using both previously published findings and entirely new data, we present evidence in support of the argument that the circadian dysfunction of advancing age in the healthy human is primarily one of failing to transduce the circadian signal from the circadian timing system (CTS) to rhythms "downstream" from the pacemaker rather than one of failing to generate the circadian signal itself. Two downstream rhythms are considered: subjective alertness and objective performance. For subjective alertness, we show that in both normal nychthemeral (24 h routine, sleeping at night) and unmasking (36 h of constant wakeful bed rest) conditions, advancing age, especially in men, leads to flattening of subjective alertness rhythms, even when circadian temperature rhythms are relatively robust. For objective performance, an unmasking experiment involving manual dexterity, visual search, and visual vigilance tasks was used to demonstrate that the relationship between temperature and performance is strong in the young, but not in older subjects (and especially not in older men).

The Gap Detection Test: Can It Be Used to Diagnose Tinnitus?

PubMed Central

Boyen, Kris; Başkent, Deniz

2015-01-01

Objectives: Animals with induced tinnitus showed difficulties in detecting silent gaps in sounds, suggesting that the tinnitus percept may be filling the gap. The main purpose of this study was to evaluate the applicability of this approach to detect tinnitus in human patients. The authors first hypothesized that gap detection would be impaired in patients with tinnitus, and second, that gap detection would be more impaired at frequencies close to the tinnitus frequency of the patient. Design: Twenty-two adults with bilateral tinnitus, 20 age-matched and hearing loss–matched subjects without tinnitus, and 10 young normal-hearing subjects participated in the study. To determine the characteristics of the tinnitus, subjects matched an external sound to their perceived tinnitus in pitch and loudness. To determine the minimum detectable gap, the gap threshold, an adaptive psychoacoustic test was performed three times by each subject. In this gap detection test, four different stimuli, with various frequencies and bandwidths, were presented at three intensity levels each. Results: Similar to previous reports of gap detection, increasing sensation level yielded shorter gap thresholds for all stimuli in all groups. Interestingly, the tinnitus group did not display elevated gap thresholds in any of the four stimuli. Moreover, visual inspection of the data revealed no relation between gap detection performance and perceived tinnitus pitch. Conclusions: These findings show that tinnitus in humans has no effect on the ability to detect gaps in auditory stimuli. Thus, the testing procedure in its present form is not suitable for clinical detection of tinnitus in humans. PMID:25822647

Calorie restriction increases cigarette use in adult smokers.

PubMed

Cheskin, Lawrence J; Hess, Judith M; Henningfield, Jack; Gorelick, David A

2005-05-01

Cigarette smokers weigh less than nonsmokers, and smokers often gain weight when they quit. This is a major barrier to smoking cessation, especially among women. However, strict dieting is not recommended during smoking cessation out of concern that it might promote relapse. This concern derives, in part, from the observation that calorie restriction increases self-administration of drugs of abuse in animals. This relationship has never been experimentally demonstrated in humans. To evaluate whether calorie restriction increases cigarette smoking in humans. Seventeen (nine males, eight females) healthy, normal-weight smokers not attempting to quit were cycled in partially counterbalanced order, double-blind, through four diets-normal calorie (2,000-2,800 kcal/day), low calorie (700 kcal/day deficit), low-carbohydrate (CHO)/normal-calorie, and low-CHO/low-calorie-for 6 days per diet in an inpatient research ward. Smoking was assessed by cigarette counts, breath carbon monoxide (CO) levels, and cigarette craving. Compared with the normal-calorie diet, while on the low-calorie diet, subjects smoked 8% more cigarettes (P<0.02) and had 11% higher breath CO levels (P<0.01). The low-CHO/normal-calorie diet showed no significant effect on either variable, but there was a 15% increase in breath CO levels (P<0.05) on the low-CHO/low-calorie diet. There were no changes in self-reported cigarette craving or mood. Consistent with animal studies, moderate calorie restriction was associated with a small but statistically significant increase in cigarette smoking, with no independent effect of CHO deprivation. These findings suggest that dieting may increase smoking behavior and could impede smoking-cessation attempts.

Use of single-nucleotide polymorphisms (SNPs) to distinguish gene expression subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

PubMed

Shimosako, Nana; Kerr, Jonathan R

2014-12-01

We have reported gene expression changes in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and the fact that such gene expression data can be used to identify subtypes of CFS/ME with distinct clinical phenotypes. Due to the difficulties in using a comparative gene expression method as an aid to CFS/ME disease and subtype-specific diagnosis, we have attempted to develop such a method based on single-nucleotide polymorphism (SNP) analysis. To identify SNP allele associations with CFS/ME and CFS/ME subtypes, we tested genomic DNA of patients with CFS/ME (n=108), patients with endogenous depression (n=17) and normal blood donors (n=68) for 504 human SNP alleles located within 88 CFS-associated human genes using the SNP Genotyping GoldenGate Assay (Illumina, San Diego, California, USA). 360 ancestry informative markers (AIM) were also examined. 21 SNPs were significantly associated with CFS/ME compared with depression and normal groups. 148 SNP alleles had a significant association with one or more CFS/ME subtypes. For each subtype, associated SNPs tended to be grouped together within particular genes. AIM SNPs indicated that 4 subjects were of Asian origin while the remainder were Caucasian. Hierarchical clustering of AIM data revealed the relatedness between 2 couples of patients with CFS only and confirmed the overall heterogeneity of all subjects. This study provides evidence that human SNPs located within CFS/ME associated genes are associated with particular genomic subtypes of CFS/ME. Further work is required to develop this into a clinically useful subtype-specific diagnostic test. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Influence of human body composition on serum peak thyrotropin (TSH) after recombinant human TSH administration in patients with differentiated thyroid carcinoma.

PubMed

Castagna, Maria Grazia; Pinchera, Aldo; Marsili, Alessandro; Giannetti, Monica; Molinaro, Eleonora; Fierabracci, Paola; Grasso, Lucia; Pacini, Furio; Santini, Ferruccio; Elisei, Rossella

2005-07-01

In this study, we evaluated the influence of height, weight, body mass index (BMI), body surface area, and body composition [total lean body mass (LBM) and fat body mass] on serum peak TSH levels obtained after recombinant human (rh)TSH. Furthermore, to verify whether the serum peak TSH influenced the efficacy of radioiodine ((131)I), we compared the rate of thyroid remnant ablation according to the patients' BMI. We studied 105 patients with differentiated thyroid carcinoma who underwent rhTSH stimulation test. Serum TSH measurements were performed before and 24, 48, and 72 h after rhTSH administration. We also compared the rate of thyroid remnant ablation among 70 differentiated thyroid carcinoma patients with different BMI. The serum peak TSH after rhTSH was significantly lower in overweight and obese subjects compared with normal-weight subjects (92.1 +/- 41.8, 82.4 +/- 24.2, and 112.7 +/- 46.3 microU/ml, respectively; P = 0.01) and in males compared with females (74.6 +/- 22.3 and 105.0 +/- 43.0 microU/ml, respectively; P = 0.0002). By univariate analysis, serum peak TSH was negatively related to weight, height, body surface area, BMI, LBM, and fat body mass, but only LBM was independently associated with serum peak TSH levels. Although it was confirmed that overweight and obese patients had a lower serum peak TSH, the rate of ablation did not differ among normal-weight, overweight, and obese patients. With this study we demonstrated that LBM is the only parameter independently associated with serum peak TSH after rhTSH administration. However, the serum peak TSH does not influence the rate of (131)I remnant ablation.

Apnea-induced rapid eye movement sleep disruption impairs human spatial navigational memory.

PubMed

Varga, Andrew W; Kishi, Akifumi; Mantua, Janna; Lim, Jason; Koushyk, Viachaslau; Leibert, David P; Osorio, Ricardo S; Rapoport, David M; Ayappa, Indu

2014-10-29

Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA. Copyright © 2014 the authors 0270-6474/14/3414571-07$15.00/0.

Adaptation of the walking pattern to uphill walking in normal and spinal-cord injured subjects.

PubMed

Leroux, A; Fung, J; Barbeau, H

1999-06-01

Lower-limb movements and muscle-activity patterns were assessed from seven normal and seven ambulatory subjects with incomplete spinal-cord injury (SCI) during level and uphill treadmill walking (5, 10 and 15 degrees). Increasing the treadmill grade from 0 degrees to 15 degrees induced an increasingly flexed posture of the hip, knee and ankle during initial contact in all normal subjects, resulting in a larger excursion throughout stance. This adaptation process actually began in mid-swing with a graded increase in hip flexion and ankle dorsiflexion as well as a gradual decrease in knee extension. In SCI subjects, a similar trend was found at the hip joint for both swing and stance phases, whereas the knee angle showed very limited changes and the ankle angle showed large variations with grade throughout the walking cycle. A distinct coordination pattern between the hip and knee was observed in normal subjects, but not in SCI subjects during level walking. The same coordination pattern was preserved in all normal subjects and in five of seven SCI subjects during uphill walking. The duration of electromyographic (EMG) activity of thigh muscles was progressively increased during uphill walking, whereas no significant changes occurred in leg muscles. In SCI subjects, EMG durations of both thigh and leg muscles, which were already active throughout stance during level walking, were not significantly affected by uphill walking. The peak amplitude of EMG activity of the vastus lateralis, medial hamstrings, soleus, medial gastrocnemius and tibialis anterior was progressively increased during uphill walking in normal subjects. In SCI subjects, the peak amplitude of EMG activity of the medial hamstrings was adapted in a similar fashion, whereas the vastus lateralis, soleus and medial gastrocnemius showed very limited adaptation during uphill walking. We conclude that SCI subjects can adapt to uphill treadmill walking within certain limits, but they use different strategies to adapt to the changing locomotor demands.

Neprilysin, obesity and the metabolic syndrome

PubMed Central

Standeven, Kristina F.; Hess, Katharina; Carter, Angela M.; Rice, Gillian I.; Cordell, Paul A.; Balmforth, Anthony J.; Lu, Bao; Scott, D. Julian; Turner, Anthony J.; Hooper, Nigel M.; Grant, Peter J.

2010-01-01

Objective Neprilysin (NEP), a zinc metallo-endopeptidase, has a role in blood pressure control and lipid metabolism. The present study tested the hypothesis that NEP is associated with insulin resistance and features of the metabolic syndrome (MetS) in a study of 318 healthy human subjects and in murine obesity and investigated NEP production by adipocytes in-vitro. Methods and Results In 318 white European males, plasma NEP was elevated in the MetS and increased progressively with increasing MetS components. Plasma NEP activity correlated with insulin, homeostasis model assessment and body mass index in all subjects (p<0.01). Quantitative RT-PCR and Western blotting showed that in human pre-adipocytes NEP expression is upregulated 25-30 fold during differentiation into adipocytes. Microarray analysis of mRNA from differentiated human adipocytes confirmed high NEP expression comparable to adiponectin and plasminogen activator inhibitor-1. In a murine model of diet-induced insulin resistance, plasma NEP levels were significantly higher in high fat diet (HFD)-fed compared with normal chow diet (NCD)-fed animals (1642±529 and 820±487 pg/μl, respectively; p<0.01). Tissue NEP was increased in mesenteric fat in HFD compared with NCD-fed mice (p<0.05). NEP knock out mice did not display any changes in insulin resistance, glucose tolerance or body and epididymal fat pad weight compared to wild type mice. Conclusions In humans, NEP activity correlated with body mass index and measures of insulin resistance with increasing levels in subjects with multiple cardiovascular risk factors. NEP protein production in human adipocytes increased during cell differentiation and plasma and adipose tissue levels of NEP were increased in obese insulin resistant mice. Our results indicate that NEP associates with cardio-metabolic risk in the presence of insulin resistance and increases in obesity. PMID:21042321

Dim light adaptation attenuates acute melatonin suppression in humans.

PubMed

Jasser, Samar A; Hanifin, John P; Rollag, Mark D; Brainard, George C

2006-10-01

Abstract Studies in rodents with retinal degeneration indicated that neither the rod nor the cone photoreceptors obligatorily participate in circadian responses to light, including melatonin suppression and photoperiodic response. Yet there is a residual phase-shifting response in melanopsin knockout mice, which suggests an alternate or redundant means for light input to the SCN of the hypothalamus. The findings of Aggelopoulos and Meissl suggest a complex, dynamic interrelationship between the classic visual photoreceptors and SCN cell sensitivity to light stimuli, relative to various adaptive lighting conditions. These studies raised the possibility that the phototransductive physiology of the retinohypothalamic tract in humans might be modulated by the visual rod and cone photoreceptors. The aim of the following two-part study was to test the hypothesis that dim light adaptation will dampen the subsequent suppression of melatonin by monochromatic light in healthy human subjects. Each experiment included 5 female and 3 male human subjects between the ages of 18 and 30 years, with normal color vision. Dim white light and darkness adaptation exposures occurred between midnight and 0200 h, and a full-field 460-nm light exposure subsequently occurred between 0200 and 0330-h for each adaptation condition, at 2 different intensities. Plasma samples were drawn following the 2-h adaptation, as well as after the 460-nm monochromatic light exposure, and melatonin was measured by radioimmunoassay. Comparison of melatonin suppression responses to monochromatic light in both studies revealed a loss of significant suppression after dim white light adaptation compared with dark adaptation (p < 0.04 and p < 0.01). These findings indicate that the activity of the novel circadian photoreceptive system in humans is subject to subthreshold modulation of its sensitivity to subsequent monochromatic light exposure, varying with the conditions of light adaptation prior to exposure.

Sensory and non-sensory factors and the concept of externality in obese subjects.

PubMed

Gardner, R M; Brake, S J; Reyes, B; Maestas, D

1983-08-01

9 obese and 9 normal subjects performed a psychophysical task in which food- or non-food-related stimuli were briefly flashed tachistoscopically at a speed and intensity near the visual threshold. A signal was presented on one-half the trials and noise only on the other one-half of the trials. Using signal detection theory methodology, separate measures of sensory sensitivity (d') and response bias (beta) were calculated. No differences were noted between obese and normal subjects on measures of sensory sensitivity but significant differences on response bias. Obese subjects had consistently lower response criteria than normal ones. Analysis for subjects categorized by whether they were restrained or unrestrained eaters gave findings identical to those for obese and normal. The importance of using a methodology that separates sensory and non-sensory factors in research on obesity is discussed.

Measurement of total and unilateral renal blood flow by oblique-angle velocity-encoded 2D-cine magnetic resonance angiography.

PubMed

Lundin, B; Cooper, T G; Meyer, R A; Potchen, E J

1993-01-01

Two independent measurements of total renal blood flow (RBF) were made in healthy human subjects (n = 14, mean age 30 yr) by CINE phase-contrast magnetic resonance angiography. RBF, measured by summing the flows measured in the right and left renal arteries, was 1152 +/- 44 ml/min (mean +/- SE). RBF, measured from the difference between supra- and infrarenal abdominal aorta flow, was 1109 +/- 68 ml/min. Regression analysis of the comparison of these two different RBF calculations yielded a correlation coefficient of 0.72 at a p < .05 level of significance. Based on other studies of RBF in normal subjects by para-aminohippuric acid (PAH) clearance, the expected RBF in this subject group was 1211 +/- 62 ml/min. The results indicate that noninvasive measurement of RBF is possible using phase-contrast magnetic resonance methods.

The effect of relative humidity of inhaled air on acoustic parameters of voice in normal subjects.

PubMed

Hemler, R J; Wieneke, G H; Dejonckere, P H

1997-09-01

The hypothesis that relative humidity (RH) of air exerts an effect on voice has been widely accepted. The aim of this study has been to assess whether this can be demonstrated. Eight healthy subjects inhaled during ten minutes three different air conditions: dry, standard room, and humidified air. After inhalation, the subjects produced repeatedly a sustained /a/ of controlled pitch and loudness, which was analyzed for perturbation and noise-to-harmonic parameters. Perturbation measures increased after inhalation of dry air. No significant differences existed between standard and humidified air. No significant difference in the noise-to-harmonic ratio was found among the three conditions. We conclude that the human voice is very sensitive to decreases in RH of inhaled air, because even after a short provocation with dry air, a significant increase in perturbation measures was found.

[Subjectivity of nursing college students' awareness of gender equality: an application of Q-methodology].

PubMed

Yeun, Eun Ja; Kwon, Hye Jin; Kim, Hyun Jeong

2012-06-01

This study was done to identify the awareness of gender equality among nursing college students, and to provide basic data for educational solutions and desirable directions. A Q-methodology which provides a method of analyzing the subjectivity of each item was used. 34 selected Q-statements from each of 20 women nursing college students were classified into a shape of normal distribution using 9-point scale. Subjectivity on the equality among genders was analyzed by the pc-QUANL program. Four types of awareness of gender equality in nursing college students were identified. The name for type I was 'pursuit of androgyny', for type II, 'difference-recognition', for type III, 'human-relationship emphasis', and for type IV, 'social-system emphasis'. The results of this study indicate that different approaches to educational programs on gender equality are recommended for nursing college students based on the four types of gender equality awareness.

Motivation and appraisal in perception of poorly specified speech.

PubMed

Lidestam, Björn; Beskow, Jonas

2006-04-01

Normal-hearing students (n = 72) performed sentence, consonant, and word identification in either A (auditory), V (visual), or AV (audiovisual) modality. The auditory signal had difficult speech-to-noise relations. Talker (human vs. synthetic), topic (no cue vs. cue-words), and emotion (no cue vs. facially displayed vs. cue-words) were varied within groups. After the first block, effects of modality, face, topic, and emotion on initial appraisal and motivation were assessed. After the entire session, effects of modality on longer-term appraisal and motivation were assessed. The results from both assessments showed that V identification was more positively appraised than A identification. Correlations were tentatively interpreted such that evaluation of self-rated performance possibly depends on subjective standard and is reflected on motivation (if below subjective standard, AV group), or on appraisal (if above subjective standard, A group). Suggestions for further research are presented.

Blood biochemical and cellular changes during decompression and simulated extravehicular activity

NASA Technical Reports Server (NTRS)

Jauchem, J. R.; Waligora, J. M.; Johnson, P. C. Jr

1990-01-01

Blood biochemical and cellular parameters were measured in human subjects before and after exposure to a decompression schedule involving 6 h of oxygen prebreathing. The exposure was designed to simulate extravehicular activity for 6 h (subjects performed exercise while exposed to 29.6 kPa). There were no significant differences between blood samples from subjects who were susceptible (n = 11) versus those who were resistant (n = 27) to formation of venous gas emboli. Although several statistically significant (P less than 0.05) changes in blood parameters were observed following the exposure (increases in white blood cell count, prothrombin time, and total bilirubin, and decreases in triglycerides, very-low-density lipoprotein cholesterol, and blood urea nitrogen), the changes were small in magnitude and blood factor levels remained within normal clinical ranges. Thus, the decompression schedule used in this study is not likely to result in blood changes that would pose a threat to astronauts during extravehicular activity.

Associations between the oxytocin receptor gene (OXTR) and "mind-reading" in humans--an exploratory study.

PubMed

Lucht, Michael J; Barnow, Sven; Sonnenfeld, Christine; Ulrich, Ines; Grabe, Hans Joergen; Schroeder, Winnie; Völzke, Henry; Freyberger, Harald J; John, Ulrich; Herrmann, Falko H; Kroemer, Heyo; Rosskopf, Dieter

2013-02-01

The application of intranasal oxytocin enhances facial emotion recognition in normal subjects and in subjects with autism spectrum disorders (ASD). In addition, various features of social cognition have been associated with variants of the oxytocin receptor gene (OXTR). Therefore, we tested for associations between mind-reading, a measure for social recognition and OXTR polymorphisms. 76 healthy adolescents and young adults were tested for associations between OXTR rs53576, rs2254298, rs2228485 and mind-reading using the "Reading the Mind in the Eyes Test" (RMET). After Bonferroni correction for multiple comparisons, rs2228485 was associated with the number of incorrect answers when subjects evaluated male faces (P =0.000639). There were also associations between OXTR rs53576, rs2254298 and rs2228485 and other RMET dimensions according to P <0.05 (uncorrected). This study adds further evidence to the hypothesis that genetic variations in the OXTR modulate mind-reading and social behaviour.

The effects of diet and physical activity on plasma homovanillic acid in normal human subjects.

PubMed

Kendler, K S; Mohs, R C; Davis, K L

1983-03-01

This study examines the effect of diet and moderate physical activity on plasma levels of the dopamine metabolite homovanillic acid (HVA) in healthy young males. At weekly intervals, subjects were fed four isocaloric meals: polycose (pure carbohydrate), sustecal, low monoamine, and high monoamine. Moderate physical activity consisted of 30 minutes of exercise on a bicycle ergometer. The effect of diet on plasma HVA (pHVA) was highly significant. Compared to the polycose meal, the high monoamine meal significantly increased pHVA. Moderate physical activity also significantly increased pHVA. Future clinical studies using pHVA in man as an index of brain dopamine function should control for the effects of both diet and physical activity.

Lack of action of prolactin suppression on the regulation of the human menstrual cycle.

PubMed

del Pozo, E; Goldstein, M; Friesen, H; Brun del Re, R; Eppenberger, U

1975-12-01

Bromocriptin (CB 154) has been found to suppress established lactation at a time when human plasma prolactin (HPRL) concentrations have already returned to the nonpregnant range. This action is due to inhibition of prolactin from the pituitary. It was then thought that a similar degree of inhibition induced during the menstrual cycle may help to uncover other possible biological actions of prolactin. In an attempt to elucidate this question eight breast-feeding mothers and seven normally menstruating volunteers underwent treatment with CB 154, including blood sampling during a sleep period. The dosage was 1 mg., three times daily, for 14 days in the first group and for a whole cycle in the normal volunteers. A control cycle preceded drug administration in the latter group. Prolactin (HPRL), growth hormone (HGH), luteotropin (LH), progesterone (PG), and estradiol (E2) were estimated (mean +/- standard error) along the menstrual cycles in the normal volunteers. HPRL and milk volumes were measured in the breast-feeding women in the base-line period and during treatment. In the postpartum group, basal HPRL had already reached normal levels prior to therapy (10.8 +/- 1.0 ng. per milliliter) and was significantly (p less than 0.002) depressed to 3.7 +/- 0.4 ng. per milliliter by CB 154. This degree of inhibition was effective in suppressing lactation within 24 to 48 hours in all of the subjects in that group. The fall in plasma HPRL from 9.5 +/- 1.5 ng. per milliliter to 3.2 +/- 0.2 ng. per milliliter observed in the normally menstruating women was similar to the one recorded in the breast-feeding group, but the sequence of hormonal changes during the menstrual cycle was not altered by treatment. The overnight study ensured around-the-clock prolactin inhibition. Results indicate no action of prolactin in the regulation of the human menstrual cycle at levels of inhibition at which a biological action of this hormone is clearly suppressed.

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

PubMed

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

2009-08-01

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

In Vitro Degradation and Fermentation of Three Dietary Fiber Sources by Human Colonic Bacteria

PubMed Central

Bliss, Donna Z.; Weimer, Paul J.; Jung, Hans-Joachim G.; Savik, Kay

2013-01-01

Although clinical benefits of dietary fiber supplementation seem to depend partially on the extent of fiber degradation and fermentation by colonic bacteria, little is known about the effect of supplemental fiber type on bacterial metabolism. In an experiment using a non-adapted human bacterial population from three normal subjects, extent of in vitro fermentation was greater for gum arabic (GA) than for psyllium (PSY), which was greater than that for carboxymethylcellulose (CMC). In a separate experiment, in vitro incubation with feces from 52 subjects with fecal incontinence, before and after random assignment to and consumption of one of three fiber (GA, PSY, or CMC) supplements or a placebo for 20-21d, indicated that prior consumption of a specific fiber source did not increase its degradation by fecal bacteria. Results suggest that the colonic microbial community enriched on a particular fiber substrate can rapidly adapt to the presentation of a new fiber substrate. Clinical implications of the findings are that intake of a fiber source by humans is not expected to result in bacterial adaptation that would require continually larger and eventually intolerable amounts of fiber to achieve therapeutic benefits. PMID:23556460

In vitro degradation and fermentation of three dietary fiber sources by human colonic bacteria.

PubMed

Bliss, Donna Z; Weimer, Paul J; Jung, Hans-Joachim G; Savik, Kay

2013-05-15

Although clinical benefits of dietary fiber supplementation seem to depend partially on the extent of fiber degradation and fermentation by colonic bacteria, little is known about the effect of supplemental fiber type on bacterial metabolism. In an experiment using a nonadapted human bacterial population from three normal subjects, the extent of in vitro fermentation was greater for gum arabic (GA) than for psyllium (PSY), which was greater than that for carboxymethylcellulose (CMC). In a separate experiment, in vitro incubation with feces from 52 subjects with fecal incontinence, before and after random assignment to and consumption of one of three fiber (GA, PSY, or CMC) supplements or a placebo for 20-21 days, indicated that prior consumption of a specific fiber source did not increase its degradation by fecal bacteria. Results suggest that the colonic microbial community enriched on a particular fiber substrate can rapidly adapt to the presentation of a new fiber substrate. Clinical implications of the findings are that intake of a fiber source by humans is not expected to result in bacterial adaptation that would require continually larger and eventually intolerable amounts of fiber to achieve therapeutic benefits.

Neuroimaging Study of the Human Amygdala - Toward an Understanding of Emotional and Stress Responses -

NASA Astrophysics Data System (ADS)

Iidaka, Tetsuya

The amygdala plays a critical role in the neural system involved in emotional responses and conditioned fear. The dysfunction of this system is thought to be a cause of several neuropsychiatric disorders. A neuroimaging study provides a unique opportunity for noninvasive investigation of the human amygdala. We studied the activity of this structure in normal subjects and patients with schizophrenia by using the face recognition task. Our results showed that the amygdala was activated by presentation of face stimuli, and negative face activated the amygdala to a greater extent than a neutral face. Under the happy face condition, the activation of the amygdala was higher in the schizophrenic patients than in control subjects. A single nucleotide polymorphism in the regulatory region of the serotonin type 3 receptor gene had modulatory effects on the amygdaloid activity. The emotion regulation had a significant impact on neural interaction between the amygdala and prefrontal cortices. Thus, studies on the human amygdala would greatly contribute to the elucidation of the neural system that determines emotional and stress responses. To clarify the relevance of the neural dysfunction and neuropsychiatric disorders, further studies using physiological, genetic, and hormonal approaches are essential.

Upregulation of 14-3-3 eta in chronic liver fluke infection is a potential diagnostic marker of cholangiocarcinoma.

PubMed

Haonon, Ornuma; Rucksaken, Rucksak; Pinlaor, Porntip; Pairojkul, Chawalit; Chamgramol, Yaovalux; Intuyod, Kitti; Onsurathum, Sudarat; Khuntikeo, Narong; Pinlaor, Somchai

2016-03-01

To discover protein markers in chronic/advanced opisthorchiasis for the early detection of Opisthorchis viverrini (OV)-associated cholangiocarcinoma (CCA). Liver tissues derived from normal hamsters and those with chronic/advanced opisthorchiasis (n = 5 per group) were subjected to 2DE and LC-MS/MS. Candidate protein expression was confirmed in hamster models and human CCA tissue microarray (TMA) using immunohistochemistry and Western blot. Proteomics analysis detected 14-3-3 eta only in infected hamsters, not in uninfected controls. Immunohistochemistry and Western blot analysis confirmed low expression of 14-3-3 eta in normal hamster livers and demonstrated increased expression through time in infected livers. This protein was also observed in parasite organs, especially during the chronic phase of opisthorchiasis. Moreover, increased expression of 14-3-3 eta, relative to normal hamster livers, was observed during the early stage of CCA induced by OV infection and administration of N-nitrosodimethylamine. Immunohistochemical analysis of human TMA revealed that 14-3-3 eta was highly expressed in CCA (84.23%, 187/222 cases) but was not found in hepatocellular carcinoma or healthy liver tissues. 14-3-3 eta protein has potential as a screening and early diagnostic marker for CCA. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls.

PubMed

Xu, Wuhua; Kawarabayashi, Takeshi; Matsubara, Etsuro; Deguchi, Kentaro; Murakami, Tetsuro; Harigaya, Yasuo; Ikeda, Masaki; Amari, Masakuni; Kuwano, Ryozo; Abe, Koji; Shoji, Mikio

2008-07-11

Antibodies to amyloid beta protein (Abeta) are present naturally or after Abeta vaccine therapy in human plasma. To clarify their clinical role, we examined plasma samples from 113 patients with Alzheimer's disease (AD) and 205 normal controls using the tissue amyloid plaque immunoreactivity (TAPIR) assay. A high positive rate of TAPIR was revealed in AD (45.1%) and age-matched controls (41.2%), however, no significance was observed. No significant difference was observed in the MMS score or disease duration between TAPIR-positive and negative samples. TAPIR-positive plasma reacted with the Abeta40 monomer and dimer, and the Abeta42 monomer weakly, but not with the Abeta42 dimer. TAPIR was even detected in samples from young normal subjects and young Tg2576 transgenic mice. Although the Abeta40 level and Abeta40/42 ratio increased, and Abeta42 was significantly decreased in plasma from AD groups when compared to controls, no significant correlations were revealed between plasma Abeta levels and TAPIR grading. Thus an immune response to Abeta40 and immune tolerance to Abeta42 occurred naturally in humans without a close relationship to the Abeta burden in the brain. Clarification of the mechanism of the immune response to Abeta42 is necessary for realization of an immunotherapy for AD.

rpb2 is a reliable reference gene for quantitative gene expression analysis in the dermatophyte Trichophyton rubrum.

PubMed

Jacob, Tiago R; Peres, Nalu T A; Persinoti, Gabriela F; Silva, Larissa G; Mazucato, Mendelson; Rossi, Antonio; Martinez-Rossi, Nilce M

2012-05-01

The selection of reference genes used for data normalization to quantify gene expression by real-time PCR amplifications (qRT-PCR) is crucial for the accuracy of this technique. In spite of this, little information regarding such genes for qRT-PCR is available for gene expression analyses in pathogenic fungi. Thus, we investigated the suitability of eight candidate reference genes in isolates of the human dermatophyte Trichophyton rubrum subjected to several environmental challenges, such as drug exposure, interaction with human nail and skin, and heat stress. The stability of these genes was determined by geNorm, NormFinder and Best-Keeper programs. The gene with the most stable expression in the majority of the conditions tested was rpb2 (DNA-dependent RNA polymerase II), which was validated in three T. rubrum strains. Moreover, the combination of rpb2 and chs1 (chitin synthase) genes provided for the most reliable qRT-PCR data normalization in T. rubrum under a broad range of biological conditions. To the best of our knowledge this is the first report on the selection of reference genes for qRT-PCR data normalization in dermatophytes and the results of these studies should permit further analysis of gene expression under several experimental conditions, with improved accuracy and reliability.

Safety of the HyperSound® Audio System in Subjects with Normal Hearing.

PubMed

Mehta, Ritvik P; Mattson, Sara L; Kappus, Brian A; Seitzman, Robin L

2015-06-11

The objective of the study was to assess the safety of the HyperSound® Audio System (HSS), a novel audio system using ultrasound technology, in normal hearing subjects under normal use conditions; we considered pre-exposure and post-exposure test design. We investigated primary and secondary outcome measures: i) temporary threshold shift (TTS), defined as >10 dB shift in pure tone air conduction thresholds and/or a decrement in distortion product otoacoustic emissions (DPOAEs) >10 dB at two or more frequencies; ii) presence of new-onset otologic symptoms after exposure. Twenty adult subjects with normal hearing underwent a pre-exposure assessment (pure tone air conduction audiometry, tympanometry, DPOAEs and otologic symptoms questionnaire) followed by exposure to a 2-h movie with sound delivered through the HSS emitter followed by a post-exposure assessment. No TTS or new-onset otological symptoms were identified. HSS demonstrates excellent safety in normal hearing subjects under normal use conditions.