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PubMed2003

Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E.

There are few data evaluating plasma and/or peripheral blood monocyte cytokine concentrations/production or attempts to manipulate proinflammatory cytokines in nonalcoholic steatohepatitis (NASH). A pilot project in a general clinical research center evaluated the effects of a step 1 American Heart Association diet plus aerobic exercise with or without 800 IU of vitamin E daily on cytokine profiles and liver enzyme levels in 16 patients with biopsy-proven NASH. Biochemical assessment of liver function, lipid profiles, and body mass index significantly improved during the first 6 weeks of therapy and remained stable during the following 6 weeks. Plasma hyaluronic acid (HA) concentrations decreased in parallel with weight loss. Plasma tumor necrosis factor (TNF) concentrations were significantly elevated in patients with NASH and similar to patients with stable alcoholic cirrhosis but not as elevated as in patients with acute alcoholic steatohepatitis (AH). Although plasma TNF, interleukin 8 (IL-8), and IL-6 concentrations were all significantly elevated compared with control values, only plasma IL-6 levels significantly decreased with therapy. Peripheral blood monocyte TNF, IL-8, and IL-6 production was significantly elevated in patients with NASH but did not significantly decrease. Independent effects of vitamin E were not observed in this small sample. In conclusion, patients with NASH have dysregulated cytokine metabolism similar to, but less pronounced than abnormalities documented in AH. Cytokine values generally did not decrease significantly with weight loss with or without vitamin E over the duration of the study. Lifestyle modifications (low-fat diet and exercise) were associated with improvement in liver enzymes, cholesterol, and plasma HA levels in patients with NASH, whereas the level of vitamin E supplementation used in this short-term pilot study provided no apparent added benefit.

Adult↗
PubMed1976

Summer day camp for multihandicapped children.

A six-week enriched sensorimotor, communication, and recreational summer day camp for twenty multihandicapped preschool children is described. The program, planned and supervised by therapists and mental retardation counselors, provided training for students who worked as camp counselors. Each counselor was assigned to work with one child and family and was responsible for assessing, establishing goals, designing appropriate programs, attending the child throughout the day, and relating to the family. The camp provided a trial for use of the Functional Skills Profile (FSP), an assessment battery designed by physical and occupational therapists to measure performance changes in low functioning, developmentally handicapped persons in order to determine the value of therapy programs. The camp is evaluated in terms of improvement in the children, the effectiveness of the student training, and parent satisfaction.

Aftercare↗
PubMed2003

Application of a case-mix classification based on the functional autonomy of the residents for funding long-term care facilities.

INTRODUCTION: increasing public costs for the care of the elderly have created fundamental changes that are redefining the basic principles of health care funding. In the past, overall institutional funding was predominantly tied to spending. In view of the limitations of this approach to funding long-term care facilities, case-mix classification tries to take into account the characteristics of the residents as a tool for predicting costs. Recently, a new case-mix classification based on the functional autonomy profile of the residents - ISO-SMAF profile - was developed in the Province of Quebec, Canada. This classification can be used to change the funding system to base it on the functional autonomy characteristics of the residents. OBJECTIVES: the main objective of this study was to apply the ISO-SMAF classification to funding long-term care facilities in one area of the Province of Quebec and to compare the results of this new funding methodology to the formal methodology. DESIGN: this study used a cross-sectional design. METHODOLOGY: the population under study comprised all residents of all 11 long-term care facilities in the Eastern Townships area of Quebec. Each resident was assessed using the Functional Autonomy Measurement System. The theoretical budget was calculated based on the adjusted cost per year associated with each ISO-SMAF profile derived from a previous economic study. RESULTS: the theoretical budget based on the ISO-SMAF profiles may highlight the under- or over-funding of a facility when compared to the usual funding system based predominantly on the number of beds and hours of care. CONCLUSION: the results of this study show the feasibility of applying the new funding approach to long-term care facilities. However, implementation of the ISO-SMAF classification for funding must be supported by continued and computerised residents' medical files including the Functional Autonomy Measurement System.

Activities of Daily Living↗
PubMed1990

Melatonin but not the ram-effect reactivates quiescent ovarian activity of mid-anestrous ewe.

The present study was conducted to examine how the social cue emanating from rams, the ram-effect, would influence the onset of melatonin-induced reproductive activity in anestrous ewes. Twenty non-lactating ewes were randomly allocated into 4 groups as follows based on a combination of the melatonin treatment (MEL) and the ram-effect (RAM): ewes of Groups A (MEL + RAM) and B (MEL) were subcutaneously implanted with melatonin capsules on April 18 (Day 0), which increased plasma melatonin levels by about 200 pg/ml for at least 5 months, while Groups C (RAM) and D (control) were untreated with melatonin. Rams were introduced to Groups A and C on Day 0, whereas Groups B and D were isolated from rams. Ovarian function of the ewe was assessed on June 9-21 (Days 52-64) by monitoring plasma progesterone (P) profiles. Luteal function (plasma P greater than 1 ng/ml for a week or longer) was evident in all the melatonin-treated ewes but only one in those untreated: 5/5 in Group A, 5/5 in Group B, 1/5 in Group C and 0/5 in Group D. By ultrasonography on Day 105 all the Group A ewes were diagnosed pregnant but none in the Group C despite that both the two groups had been run with rams. These results indicate that chronic melatonin treatment is capable of advancing the reproductive recrudescence in seasonally anestrous ewes, and that progonadal effects of rams are subtle, if any, during the mid-anestrous period.

Anestrus↗
PubMed2006

Effects of various soya protein hydrolysates on lipid profile, blood pressure and renal function in five-sixths nephrectomized rats.

Studies have demonstrated that isolated soya protein (ISP) can slow the progression of renal injury, reduce blood pressure and improve the serum lipid profile in experimental animals and human subjects. The mechanisms and components of soya responsible have not been fully established. The present study was designed to evaluate the effects of the hydrophilic supernatant fraction (SF) and the hydrophobic precipitate fraction (PF) isolated from soya protein hydrolysate on renal function, lipid metabolism and blood pressure in five-sixths nephrectomized rats. Experimental animals were subjected to a nephrectomy and allocated to four groups (180 g casein/kg, 180 g ISP/kg, 100 g casein/kg with 80 g SF/kg, and 100 g casein/kg with 80 g PF/kg). The SF group had the most significant decreases in blood pressure and total cholesterol, as well as a significantly retarded progression of the experimentally induced renal disease, compared with the other groups. The PF group exhibited a significantly increased faecal excretion of total steroids. The serum creatinine, level of proteinuria, total cholesterol and LDL-cholesterol concentrations, and blood pressure were significantly reduced, and HDL-cholesterol was significantly increased, in the ISP and PF groups compared with the casein group, but no significant differences were observed between the ISP and PF groups. These results suggest that both soya protein hydrolysate fractions favourably affected chronic renal failure induced by a five-sixths nephrectomy, and the hydrophilic fraction of soya protein hydrolysate had the most pronounced effect on attenuating hypertension and slowing the progression of renal disease.

Animals↗
PubMed2000

Human leptin enhances activation and proliferation of human circulating T lymphocytes.

Leptin is an adipocyte-secreted hormone that centrally regulates weight control. However, leptin receptor is expressed not only in the central nervous system, but also in other systems such as reproductive and hematopoietic tissues. Human leptin has previously been shown to enhance cytokine production by murine peritoneal macrophages and human circulating monocytes. In this paper we have assessed the presence of leptin receptors in peripheral human T lymphocytes and we have studied their functional role. Both CD4(+) and CD8(+) T lymphocytes express leptin receptors. Moreover, we show that human leptin dose-dependently enhances proliferation and activation of human circulating T lymphocytes when they are costimulated by PHA or Con A. Leptin alone was not able to activate T lymphocytes. To confirm a direct effect of leptin on T lymphocytes, monocytes were extracted by adhesion to culture flasks. The early activation surface marker CD69 was then induced in both CD4(+) and CD8(+) T lymphocytes after 8 h stimulation with PHA or Con A. Leptin dose-dependently enhanced stimulated CD69 expression. Moreover, leptin dose-dependently enhanced the expression of the late activation markers CD25 and CD71 in both CD4(+) and CD8(+) T lymphocytes after 48 h stimulation with PHA or Con A. Finally, we have found that leptin modulates CD4(+) T lymphocyte activation toward Th1 phenotype by stimulating the synthesis of IL-2 and IFN-gamma. These results demonstrate the presence of the leptin receptor in human circulating CD4(+) and CD8(+) T lymphocytes and a functional role of leptin as a modulator (enhancer) of lymphocyte stimulation with a shift toward Th1 cytokine-production profile. This function of leptin may have some relevance in the pathophysiology of immunologic alterations related to obesity.

Antigens, CD↗
PubMed1990

Study of the topography of cannabinoids in model membranes using X-ray diffraction.

Small-angle X-ray diffraction was used to determine the topography of (-)-delta 8-tetrahydrocannabinol in partially hydrated dimyristoylphosphatidylcholine bilayers. Electron density profiles of lipid bilayers in the presence and absence of the cannabinoid were calculated using Fourier transform. Step-function equivalent profiles were then constructed to obtain the absolute electron density scale. We have compared the electron density profiles of the above preparations to determine the location of the drug molecule in the bilayer. By using (-)-5'-iodo-delta 8-tetrahydrocannabinol in parallel experiments, we were also able to locate the iodine atom in the bilayer and deduce the conformation of the cannabinoid side alkyl chain. All comparisons were made between different preparations having the same mesomorphic form and total period repeat distance. To achieve this, we have carried out X-ray diffraction experiments at various temperatures to cover the different mesomorphic phases and combined our data with the corresponding results from differential scanning calorimetry. Based on the results of this work and previous data on the orientation of the cannabinoid in model membranes, we concluded that the phenolic hydroxy group of the drug molecule exists near the carbonyl groups of DMPC and that the average position of the iodine atom is approx. 5.5 A from the center (terminal methyl region) of the DMPC bilayer. This requires the cannabinoid side-chain to assume an orientation parallel to the bilayer chains.

Calorimetry, Differential Scanning↗
PubMed1999

Improving the quality of institutional care of urinary incontinence among the elderly: a challenge for governmental regulation.

This article describes actual UI prevalence and quality of care at Israeli LTC institutions for the elderly. The analysis is based on current regulatory data on 14,406 residents at 196 residential homes, and 8,278 patients at 159 hospitals for the chronically ill. It includes a calculation of summary indices of quality, the percentage of institutions with deficient items and of those showing change, and a description of functional status profiles. Multiple regression explains the deficiency rate variance through independent institutional variables. There is a higher prevalence of severe functional impairment and full incontinence at hospitals for the chronically ill than at residential homes. There were higher rates of deficiencies and lower rates of corrections for structural items than for process items at both. A major improvement occurred for process items (50-100 per cent). Regarding outcomes, 34 percent of the residents with UI during the first assessment were continent two years later.

Activities of Daily Living↗
PubMed2001

Local-functional theory of critical adsorption.

Local-functional methods are applied to critical adsorption in three-dimensional Ising-like systems. The universal order-parameter-profile scaling functions, P(+/-)(x), along the critical isochore (+) and phase boundary (-), are calculated along with their associated universal amplitudes. Good agreement is found with the results of Monte Carlo simulations. General properties of P(+/-)(x) for small and large scaled distance, x, are elucidated. An order-parameter scaling function, P(c)(x), for critical adsorption along the critical isotherm is introduced and calculated.

Journal Article↗
PubMed2004

Pulmonary functions in patients with type 2 diabetes mellitus & correlation with anthropometry & microvascular complications.

BACKGROUND & OBJECTIVES: The purpose of this study was to evaluate pulmonary functions including respiratory muscle strength in patients with type 2 diabetes mellitus (T2DM) and to determine their correlations with anthropometric profile, glycaemic control, and microangiopathic diabetic complications. METHODS: Twenty nine patients with T2DM and 11 healthy control subjects were divided into the following three groups; (i) T2DM patients with any or a combination of microangiopathy(ies) (retinopathy, nephropathy, and peripheral neuropathy) (group 1, n=12); (ii) T2DM patients without any complications (group 2, n = 17); and (iii) a healthy control group (group 3, n=11). All patients were assessed with anthropometry, glycosylated haemoglobin (HbA1C), and lipid profile. Pulmonary functions were measured by spirometry. Pulmonary diffusion capacity for carbon monoxide (DLco) was measured by the steady state method. The presence of diabetic nephropathy was determined by 24 h protein excretion. RESULTS: A significant reduction of DLco was observed in group 1 (P<0.001), as compared to the other groups. There were no differences among the three groups for other pulmonary functions; forced vital capacity, forced expired volume in one second, peak expiratory flow rate, and maximal static inspiratory and expiratory pressures. Significant correlations were observed between DLco and the following parameters in group 1; HbA1c (r=0.62, P<0.05), total cholesterol level (r = -0.44, P<0.05) and creatinine clearance (r=0.42, P<0.05). INTERPRETATION & CONCLUSION: The present study shows that the impairment of pulmonary diffusion capacity for carbon monoxide was common in T2DM Asian Indian patients having microangiopathy. Pathophysiologically, it could be related to glycaemic control or dyslipidaemia. Correlation of % BF with DLCo needs to be explored further.

Adult↗
PubMed1991

[A correlational analysis of the EEG rhythms and functional hemispheric asymmetry in children with the hyperdynamic syndrome].

Thirty-three mentally normal children aged 4.5 to 11 years with hyperdynamia were examined for their EEG. In the profile of functional asymmetry (PFA) detected by the leading hand and eye, a considerable portion, as compared to normals, was made up of ambidextrous children with no left-handers. Depending on the pattern of biopotentials, two types were distinguished in the EEG. Each of the type covered children with different PFA. The cross-correlations inside and interhemispheric relations were different in children with different PFA and depended on the EEG type. The children with hyperdynamia were shown to have the weakening of the intrahemispheric correlations by the alpha rhythm together with their potentiation according to the beta rhythms, a decrease of positive interhemispheric asymmetries, and a great number of negative asymmetries.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

Effect of meditation on respiratory system, cardiovascular system and lipid profile.

In this study, respiratory functions, cardiovascular parameters and lipid profile of those practicing Raja Yoga meditation (short and long term meditators) were compared with those of nonmediators. Vital capacity, tidal volume and breath holding were significantly higher in short and long term meditators than nonmeditators. Long term mediators had significantly higher vital capacity and expiratory pressure than short term meditators. Diastolic blood pressure was significantly lower in both short and long term meditators as compared to nonmeditators. Heart rate was significantly lower in long term meditators than in short term meditators and nonmeditators. Lipid profile showed a significant lowering of serum cholesterol in short and long term meditators as compared to nonmeditators. Lipid profile of short and long term meditators was better than the profile of nonmeditators inspite of similar physical activity. This shows that Raja Yoga meditation provides significant improvements in respiratory functions, cardiovascular parameters and lipid profile.

Adult↗
PubMed2006

Cyclin D1 determines mitochondrial function in vivo.

The cyclin D1 gene encodes a regulatory subunit of the holoenzyme that phosphorylates and inactivates the pRb tumor suppressor to promote nuclear DNA synthesis. cyclin D1 is overexpressed in human breast cancers and is sufficient for the development of murine mammary tumors. Herein, cyclin D1 is shown to perform a novel function, inhibiting mitochondrial function and size. Mitochondrial activity was enhanced by genetic deletion or antisense or small interfering RNA to cyclin D1. Global gene expression profiling and functional analysis of mammary epithelial cell-targeted cyclin D1 antisense transgenics demonstrated that cyclin D1 inhibits mitochondrial activity and aerobic glycolysis in vivo. Reciprocal regulation of these genes was observed in cyclin D1-induced mammary tumors. Cyclin D1 thus integrates nuclear DNA synthesis and mitochondrial function.

Animals↗
PubMed1992

Effects of training on iron status in cross-country skiers.

Haematological changes were studied in cross-country skiers during a 33-week training season (7 h a week). The daily amounts of training were calculated from the duration and the intensity of the exercise and then used to estimate training responses associated with a first order transfer function. The profile of system training responses (STR) was determined by convolution between the amounts of training and a first-order transfer function. Linear regressions were used to determine correlation coefficients between STR and iron status indices. Among the values for the time constants of decay, the one giving the best fit between STR and iron status indices was chosen. A relationship was noted between on the one hand STR and changes in serum ferritin concentration ([FERR]) and on the other hand STR and change in mean cell volume (MCV). The [FERR] was decreased and MCV was increased by training. It is suggested that a decrease in [FERR] could have been related to a decrease in total body iron stores. However, large and rapid changes in [FERR] could not have been a reflection of changes in total body iron stores. Equilibrium between [FERR] and total body iron stores could have been temporarily altered by the effects of training. Moreover, iron stores did not seem to have been sufficiently depleted to restrict erythropoiesis. The MCV increased slightly in response to intense training suggesting that training enhances the proportion of young erythrocytes.

Adolescent↗
PubMed1995

Psychophysiologic factors contributing to functional performance in people with COPD: are there gender differences?

The purpose of this study was to compare the functional performance profiles of men and women with chronic obstructive pulmonary disease, describe the extent to which physiologic impairment, physical symptoms, and psychosocial resources contribute in a cumulative manner to performance, and outline the extent to which these contributions differ across gender. Secondary data analyses were employed. Although women (n = 45) reported more functional difficulty than men (n = 44) in 9 of 12 Sickness Impact Profile categories, the differences were not significant. Using hierarchical regression procedures, physiologic, symptomatic, and interactive variables predicted total (R2 = .64) and physical performance (R2 = .52), while symptomatic and psychosocial variables predicted psychosocial performance (R2 = .53). Results indicate that models of functional performance may be different for men and women.

Adaptation, Psychological↗
PubMed2005

Global profiling of Shewanella oneidensis MR-1: expression of hypothetical genes and improved functional annotations.

The gamma-proteobacterium Shewanella oneidensis strain MR-1 is a metabolically versatile organism that can reduce a wide range of organic compounds, metal ions, and radionuclides. Similar to most other sequenced organisms, approximately 40% of the predicted ORFs in the S. oneidensis genome were annotated as uncharacterized "hypothetical" genes. We implemented an integrative approach by using experimental and computational analyses to provide more detailed insight into gene function. Global expression profiles were determined for cells after UV irradiation and under aerobic and suboxic growth conditions. Transcriptomic and proteomic analyses confidently identified 538 hypothetical genes as expressed in S. oneidensis cells both as mRNAs and proteins (33% of all predicted hypothetical proteins). Publicly available analysis tools and databases and the expression data were applied to improve the annotation of these genes. The annotation results were scored by using a seven-category schema that ranked both confidence and precision of the functional assignment. We were able to identify homologs for nearly all of these hypothetical proteins (97%), but could confidently assign exact biochemical functions for only 16 proteins (category 1; 3%). Altogether, computational and experimental evidence provided functional assignments or insights for 240 more genes (categories 2-5; 45%). These functional annotations advance our understanding of genes involved in vital cellular processes, including energy conversion, ion transport, secondary metabolism, and signal transduction. We propose that this integrative approach offers a valuable means to undertake the enormous challenge of characterizing the rapidly growing number of hypothetical proteins with each newly sequenced genome.

Gene Expression Profiling↗
PubMed2005

Extracting meaning from functional genomics experiments.

The completion of draft genome sequences for human, mouse, rat, and an increasing number of other species, has provided us with preliminary gene catalogues for many organisms of medical and scientific interests. Interpreting these gene lists in the context of the organism's underlying biology, however, remains difficult. The development of DNA microarrays provided one potential source of data to help interpret gene function; by profiling global patterns of gene expression across diverse conditions, it was hoped that we might be able to develop insight into biological function. But the power of these functional genomics assays, as well as assays in proteomics and metabolomics, is that they primarily give us lists of differentially expressed genes that can be correlated with particular phenotypic states, but which remain difficult to link mechanistically to the biology driving the phenotype.

Animals↗
PubMed1994

The three-dimensional profile method using residue preference as a continuous function of residue environment.

In the 3-dimensional profile method, the compatibility of an amino acid sequence for a given protein structure is scored as the sum of the preferences of the residues for their environments in the 3D structure. In the original method (Bowie JU, Lüthy R, Eisenberg D, 1991, Science 253:164-170), residue environments were quantized into 18 discrete environmental classes. Here, amino acid residue preferences are expressed as a continuous function of environmental variables (residue area buried and fractional area buried by polar atoms). This continuous representation of residue preferences, expressed as a Fourier series, avoids the abrupt change of preference of residues in slightly different environments, as encountered in the original method with its 18 discrete environmental classes. When compared with the discrete 18-class representation of residue environments, this continuous 3D profile is found to be more sensitive in identifying sequences that fold into the profiled structure but share with it little sequence identity. The continuous 3D profile is also less sensitive to errors in environmental variables than is the discrete 3D profile. The continuous 3D profile can also be used to detect wrong folds or incorrectly modeled segments in an otherwise correct structure, as could the discrete 3D profile (Lüthy R, Bowie JU, Eisenberg D, 1992, Nature 356:83-85). Moreover, the progress of structure improvement during atomic refinement can also be monitored by examining the profile scores in a moving-window scan. Finally, by defining a functional form for profile scores, we open the way to profile atomic refinement in which an atomic structure adjusts to produce residue environments more compatible with the protein side chains.

Amino Acids↗