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Biomedical subjects

S Klein

Publications and source records attributed to S Klein.

At least 91 records · Page 5Linked to original sources
PubMed2000

Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training.

Endurance training increases fatty acid oxidation (FAO) and skeletal muscle oxidative capacity. However, the source of the additional fat and the mechanisms for increasing FAO capacity in muscle are not clear. We measured whole body and regional lipolytic activity and whole body and plasma FAO in six lean women during 90 min of bicycling exercise (50% pretraining peak O(2) consumption) before and after 12 wk of endurance training. We also assessed skeletal muscle content of peroxisome proliferator-activated receptor-alpha (PPARalpha) and its target proteins that regulate FAO [medium-chain and very long chain acyl-CoA dehydrogenase (MCAD and VLCAD)]. Despite a 25% increase in whole body FAO during exercise after training (P < 0.05), training did not alter regional adipose tissue lipolysis (abdominal: 0.56 +/- 0.26 and 0.57 +/- 0.10 micromol x 100 g(-1) x min(-1); femoral: 0.13 +/- 0.07 and 0.09 +/- 0.02 micromol x 100 g(-1) x min(-1)), whole body palmitate rate of appearance in plasma (168 +/- 18 and 150 +/- 25 micromol/min), and plasma FAO (554 +/- 61 and 601 +/- 45 micromol/min). However, training doubled the levels of muscle PPARalpha, MCAD, and VLCAD. We conclude that training increases the use of nonplasma fatty acids and may enhance skeletal muscle oxidative capacity by PPARalpha regulation of gene expression.

Acyl-CoA Dehydrogenase↗
PubMed2000

Racial differences in lipid metabolism in women with abdominal obesity.

We evaluated palmitate rate of appearance (R(a)) in plasma during basal conditions and during a four-stage epinephrine infusion plus pancreatic hormonal clamp in nine white and nine black women with abdominal obesity, who were matched on fat-free mass, total and percent body fat, and waist-to-hip circumference ratio. On the basis of single-slice magnetic resonance imaging analysis, black women had the same amount of subcutaneous abdominal fat but less intra-abdominal fat than white women (68 +/- 9 vs. 170 +/- 14 cm(2), P < 0.05). Basal palmitate R(a) was lower in black than in white women (1.95 +/- 0.26 vs. 2.88 +/- 0.23 micromol. kg fat-free mass(-1). min(-1), P < 0.005), even though plasma insulin and catecholamine concentrations were the same in both groups. Palmitate R(a) across a physiological range of plasma epinephrine concentrations remained lower in black women, because the increase in palmitate R(a) during epinephrine infusion was the same in both groups. We conclude that basal and epinephrine-stimulated palmitate R(a) is lower in black than in white women with abdominal obesity. The differences in basal palmitate kinetics are not caused by alterations in plasma insulin or catecholamine concentrations or lipolytic sensitivity to epinephrine. The lower rate of whole body fatty acid flux and smaller intra-abdominal fat mass may have clinical benefits because of the relationship between excessive fatty acid availability and metabolic diseases.

Abdomen↗
PubMed2000

Oxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity.

We evaluated plasma fatty acid availability and plasma and whole body fatty acid oxidation during exercise in five lean and five abdominally obese women (body mass index = 21 +/- 1 vs. 38 +/- 1 kg/m(2)), who were matched on aerobic fitness, to test the hypothesis that obesity alters the relative contribution of plasma and nonplasma fatty acids to total energy production during exercise. Subjects exercised on a recumbent cycle ergometer for 90 min at 54% of their peak oxygen consumption. Stable isotope tracer methods ([(13)C]palmitate) were used to measure fatty acid rate of appearance in plasma and the rate of plasma fatty acid oxidation, and indirect calorimetry was used to measure whole body substrate oxidation. During exercise, palmitate rate of appearance increased progressively and was similar in obese and lean groups between 60 and 90 min of exercise [3.9 +/- 0.4 vs. 4.0 +/- 0.3 micromol. kg fat free mass (FFM)(-1). min(-1)]. The rate of plasma fatty acid oxidation was also similar in obese and lean subjects (12.8 +/- 1.7 vs. 14.5 +/- 1.8 micromol. kg FFM(-1). min(-1); P = not significant). However, whole body fatty acid oxidation during exercise was 25% greater in obese than in lean subjects (21.9 +/- 1.2 vs. 17.5 +/- 1.6 micromol. kg FFM(-1). min(-1); P < 0.05). These results demonstrate that, although plasma fatty acid availability and oxidation are similar during exercise in lean and obese women, women with abdominal obesity use more fat as a fuel by oxidizing more nonplasma fatty acids.

Abdomen↗
PubMed2000

Effect of pinitol treatment on insulin action in subjects with insulin resistance.

OBJECTIVE: Endogenous low-molecular-weight glycans containing pinitol (3-O-methyl-D-chiro-inositol) and D-chiro-inositol are thought to mediate certain actions of insulin. We tested the hypothesis that oral administration of soybean-derived pinitol would improve insulin sensitivity in obese subjects (BMI = 36.6 kg/m2) with diet-treated type 2 diabetes or glucose intolerance (HbA1c = 6.8%). RESEARCH DESIGN AND METHODS: There were 22 subjects randomized to receive either pinitol 20 mg x kg(-1) x day(-1) (n = 12) or placebo (n = 10) in a 28-day double-blinded trial. RESULTS: No toxicity due to the pinitol was observed during the study The sensitivity of glucose and lipid metabolism to insulin were assessed by measurement of whole-body glucose, palmitate, and glycerol kinetics during basal conditions and a hyperinsulinemic-euglycemic clamp. Metabolic measurements were made at baseline and again at the end of the study Final plasma levels of pinitol were 48-fold (1.06 +/- 0.15 vs. 0.02 +/- 0.01 micromol/l, P < 0.0001) and D-chiro-inositol levels 14-fold (0.56 +/- 0.08 vs. 0.04 +/- 0.02 micromol/l, P < 0.0001) greater in the pinitol group compared with placebo. CONCLUSIONS: Four weeks of pinitol treatment did not alter baseline glucose production, insulin-mediated glucose disposal, or rates of appearance of free fatty acids and glycerol in plasma. We conclude that plasma levels of both pinitol and D-chiro-inositol are very responsive to pinitol ingestion, but insulin sensitivity does not increase after pinitol treatment in individuals with obesity and mild type 2 diabetes.

Blood Glucose↗
PubMed2000

Cytotoxic hepatosplenic gammadelta T-cell lymphoma following acute myeloid leukemia bearing two distinct gamma chains of the T-cell receptor. Biologic and clinical features.

BACKGROUND AND OBJECTIVES: Hepatosplenic gd T-cell lymphoma is a rare entity of peripheral T-cell lymphomas. We characterized in detail the first case of hepatosplenic gd -T-cell lymphoma following acute myeloid leukemia. DESIGN AND METHODS: Hepatosplenic gd -T-cell lymphoma was diagnosed in a woman who had been in complete remission (CR) of acute myeloid leukemia (AML) for two years. Improvement but no objective response of the disease was observed after various types of chemotherapy. CR was achieved after related donor stem cell transplantation. Thirteen months later relapse of hepatosplenic gd T-cell lymphoma was diagnosed. While being prepared for a second transplantation the patient developed meningeal lymphoma and died. The patient's lymphoma cells were studied by immunologic, functional and molecular techniques. RESULTS: Lymphoma cells expressed the gd T-cell receptor (TCR), CD2, CD3, CD5, CD7, CD38, CD45, CD161 (NKR-P1), TIA and Ki67. Further analysis revealed expression of Vd1 and two distinct TCRg chains, Vg3 and Vg9, by the malignant cell clone. The clonality of the T-cells was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) followed by sequencing of TCR Vg3, Vg9 and Vd1 junctional regions. Clone-specific PCR was negative at diagnosis of AML and was positive at all times during follow-up of the hepatosplenic gd T-cell lymphoma. The lymphoma cells mediated strong natural killer cell-like cytotoxic activity, possibly explained by expression of CD161 and a lack of killer inhibitory receptor. INTERPRETATION AND CONCLUSIONS: Several so far undescribed features were observed in this case of hepatosplenic gd T-cell lymphoma, such as T-cell lymphoma following AML, expression of two distinct T-cell receptor g-chains, and an unexpected cytotoxic phenotype.

Acute Disease↗
PubMed2000

Personal safety and the abuse of staff in a Scottish NHS Trust.

BACKGROUND: An employer's 'duty of care' is enshrined in statute and common law. This responsibility extends to identifying areas of risk to employee's safety and emotional well being. OBJECTIVE: To identify the views of NHS staff on their safety and exposure to assault and other forms of abuse. DESIGN: A survey by questionnaire and semi-structured interview of the staff of an NHS Trust. SETTING: A large Scottish NHS Trust. SUBJECTS: All 5365 staff of the Trust. RESULTS: Two thousand two hundred and ninety four (43%) employees contributed to this survey. With regard to exposure to hazardous substances and serious infection, most staff were satisfied with safety standards and guidelines. Over a 12 month period 23% of the workforce had been assaulted, mainly by patients and 63% had experienced verbal abuse, again, mainly from patients. There were differences among occupational groups but overall 16% had been bullied; 18% had suffered discrimination; 22% had experienced harassment, and 13% had been victimized. Only 42% of individuals reported their most distressing incidents; 56% of them regarded the outcome of their reports as satisfactory. CONCLUSIONS: Staff are generally satisfied with the steps taken to safeguard them against hazardous substances and serious infection. Assault by and abuse from patients is a considerable risk, especially for trained nurses. In terms of bullying, harassment, discrimination and victimization, the abuse of power by colleagues is also a distressing and under-reported phenomenon which needs to be addressed by regular audit and the creation of a climate in which employees feel secure enough to report such abuse and to have faith in the mechanisms set up to deal with such complaints.

Attitude of Health Personnel↗
PubMed1999

DPC4/SMAD4 mediated tumor suppression of colon carcinoma cells is associated with reduced urokinase expression.

We recently identified DPC4/Smad4 as a candidate tumor suppressor gene mutated or lost in one half of pancreatic carcinomas and in a subset of colon and biliary tract carcinomas. DPC4 plays a key role in signal transduction of the TGF-beta superfamily of molecules and inactivation of TGF-beta mediated growth inhibition is supposed to be the driving force for DPC4 inactivation in human tumors. However, DPC4 mediated tumor suppression by reconstitution of defective cells has not yet been reported. Here we show suppression of tumorigenicity in nude mice by stable reexpression of DPC4 in SW480 colon carcinoma cells. In vitro growth of DPC4-transfected cells was not affected and resistance towards TGF-beta mediated growth inhibition was retained. Instead, cells exhibited morphological alterations and adhesion and spreading were accelerated. These phenotypic changes were associated with reduced expression levels of the endogenous urokinase-type plasminogen activator (uPA) and plasminogen-activator-inhibitor-1 (PAI-1) genes, the products of which are implicated in the control of cell adhesion and invasion. In patients, high expression levels of uPA and PAI-1 correlate with poor prognosis. Thus, reduced expression of uPA and PAI-1 is consistent with suppression of tumorigenicity in DPC4 reconstituted cells. These results demonstrate DPC4's tumor suppressive function and suggest a potential role for DPC4 as a modulator of cell adhesion and invasion.

Animals↗
PubMed1999

A fast method to diagnose chromosome and plasmid loss in Saccharomyces cerevisiae strains.

We have developed a simple, fast and reliable method for the analysis of genetic stability in budding yeast strains. The assay relies on our previous finding that cells expressing the green fluorescent protein (GFP) can be detected and counted by flow cytometric analysis (FACS) (Niedenthal et al., 1996). Expression of a gfp-carrying CEN-plasmid in a wild-type strain resulted in the emission of strong fluorescence from 80% of the cell population. Strong fluorescence and presence of the plasmid, determined by the presence of the URA3 genetic marker, was strictly correlated. Expression of this plasmid in 266 yeast strains, each carrying a complete deletion of a novel, non-essential gene identified in the S. cerevisiae sequencing project, pinpointed 12 strains with an increased level of mitotic plasmid loss. Finally we have shown that measurement of mitotic loss of artificial chromosome fragments equipped with the gfp expression cassette can be performed quantitatively using FACS.

Chromosome Segregation↗
PubMed1999

Systematic analysis of S. cerevisiae chromosome VIII genes.

To begin genome-wide functional analysis, we analysed the consequences of deleting each of the 265 genes of chromosome VIII of Saccharomyces cerevisiae. For 33% of the deletion strains a growth phenotype could be detected: 18% of the genes are essential for growth on complete glucose medium, and 15% grow significantly more slowly than the wild-type strain or exhibit a conditional phenotype when incubated under one of 20 different growth conditions. Two-thirds of the mutants that exhibit conditional phenotypes are pleiotropic; about one-third of the mutants exhibit only one phenotype. We also measured the level of expression directed by the promoter of each gene. About half of the promoters direct detectable transcription in rich glucose medium, and most of these exhibited only low or medium activity. Only 1% of the genes are expressed at about the same level as ACT1. The number of active promoters increased to 76% upon growth on a non-fermentable carbon source, and to 93% in minimal glucose medium. The majority of promoters fluctuated in strength, depending on the medium.

DNA Primers↗
PubMed1999

Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by a systematic approach.

In a systematic approach to the study of Saccharomyces cerevisiae genes of unknown function, 150 deletion mutants were constructed (1 double, 149 single mutants) and phenotypically analysed. Twenty percent of all genes examined were essential. The viable deletion mutants were subjected to 20 different test systems, ranging from high throughput to highly specific test systems. Phenotypes were obtained for two-thirds of the mutants tested. During the course of this investigation, mutants for 26 of the genes were described by others. For 18 of these the reported data were in accordance with our results. Surprisingly, for seven genes, additional, unexpected phenotypes were found in our tests. This suggests that the type of analysis presented here provides a more complete description of gene function.

Cell Differentiation↗
PubMed1999

Activity of O6-methylguanine DNA methyltransferase in mononuclear blood cells of formaldehyde-exposed medical students.

A recent study reported that exposure of student embalmers in Cincinnati to high concentrations of formaldehyde (2 mg/m3) reduced the activity of the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT). Reduction in a DNA repair enzyme may strongly increase the cancer risk not only with respect to the repair-enzyme causing agent but with respect to all carcinogens causing lesions subject to repair by the enzyme in question. Thus, we examined whether formaldehyde exposure of 57 medical students during their anatomy course at two different Universities in Germany influenced MGMT activity in mononuclear blood cells. Mean formaldehyde exposure of 41 students was 0.2 +/- 0.05 mg/m3 for 6 h per week. MGMT activity was 133.2 +/- 14.9 fmol MGMT/10(6) cells before the beginning of the formaldehyde exposure, 131.1 +/- 15.8 fmol MGMT/10(6) cells after 50 days (P = 0.56) and 128.2 +/- 19.0 fmol MGMT/10(6) cells after 111 days of exposure (P = 0.92). Similarly, no significant influence of formaldehyde exposure was observed, when smoking habits, alcohol consumption, allergic disease and sex of students were considered. In addition no significant difference was obtained in MGMT activity between 16 students with mean formaldehyde exposure of 0.8 +/- 0.6 mg/m3 and students without formaldehyde exposure (n = 51; P = 0.37). In conclusion, exposure of the medical students in western Europe to formaldehyde did not decrease MGMT activity in mononuclear blood cells.

Adult↗
PubMed1999

The effects of the participation of patients with cancer in teaching communication skills to medical undergraduates: a randomised study with follow-up after 2 years.

The importance of good doctor-patient communication is widely recognised. The aims of this study were to evaluate the immediate effects of the participation of patients with cancer on the attitudes and skills of undergraduate medical students receiving an interview skills training programme, and to assess the effects of the participation of patients with cancer on the attitudes and interview performance of students 2 years later. It was hypothesised that the participation of cancer patients would have specific beneficial effects on attitudes and interview performance. Before participating in a 6-session interview methods course in third year, students were randomised to be taught with patients who had cancer (experimental group) or with patients with other diagnoses (control group). Before and after participating in the course, 233 students (94% response rate) completed an Attitudes Questionnaire. When they reached their fifth year, 54 students again completed the Attitudes Questionnaire and, in addition, made a video recording of an interview with a patient who had gynaecological cancer. These recordings were rated independently by two researchers using the Interview Rating Instrument. Immediately after the course, a number of differences were found between the two groups. For example, students in the experimental group were more likely to consider the ability to listen an extremely important characteristic of hospital doctors and to consider more strongly that trust is an essential part of the doctor-patient relationship. 2 years after the course, the ability of hospital doctors to communicate with patients, and the need for clinical decisions to reflect patients' wishes, were considered to be more important by students in the experimental group, although even 96% of controls felt both these issues were very or extremely important. As hypothesised, the experimental group had better ratings in terms of responding empathically, showing regard and concern for the patient, and assessing the impact of the symptoms on the patient's life. The participation of patients with cancer has beneficial and enduring effects on the attitudes and interview performance of medical undergraduates. Medical schools should consider how best patients with cancer can make an important contribution to communication skills training.

Clinical Competence↗
PubMed1999

IL-10 expression by CT26 colon carcinoma cells inhibits their malignant phenotype and induces a T cell-mediated tumor rejection in the context of a systemic Th2 response.

In spite of the evidence that IL-10 has Th1-immunosuppressive and anti-inflammatory effects, it has been shown that IL-10 may reduce the tumorigenic capacity of certain tumor cell types. In order to characterize the responses elicited by IL-10, we explored the effect of transducing murine CT26 colon carcinoma cells with a recombinant retrovirus expressing mIL-10. IL-10 gene transfer of CT26 cells had no effect on tumor cell growth on plastic surface but inhibited the anchorage-independent growth capacity of tumor cells and their metastatic potential as assessed by their invasive and migration ability. Expression of IL-10 also elicited an antitumor immune response involving both CD4+ and CD8+ T cells. Assessment of the immune status of the animals demonstrated that mice injected with CT26-IL10 cells showed prevalence of a systemic and tumor-specific Th2 response. Spleen cells obtained from these mice showed an increased production of IL-4 and no changes in IFNgamma levels, characteristic of a Th2 response. These results demonstrate that IL-10 affects CT26 tumor cell growth by both inhibiting the malignant phenotype and by recruiting and activating a T cell-mediated antitumor response. This T cell response occurs in the context of a shift towards a Th2 response.

Analysis of Variance↗
PubMed1999

A multicentre evaluation of the laser assisted ratio analyser (LARA): a novel device for measurement of 13CO2 in the 13C-urea breath test for the detection of Helicobacter pylori infection.

BACKGROUND: The laser assisted ratio analyser (LARA) was developed as a novel device to measure 13CO2 in the urea breath test for the detection of H. pylori infection. The analyser was tested in a prospective multicentre study in 444 patients in North America (Phase 1) followed by second study involving 160 patients (Phase 2). METHODS: Patients undergoing endoscopy for clinical indications had antral and gastric biopsies taken for histological examination, culture and CLO test. One hour after endoscopy, a baseline breath sample was obtained, 100 mg of 13C-urea were ingested and breath samples were obtained at 30 and 60 min post ingestion. Data obtained with the LARA were compared with the results of culture, rapid urease testing and central pathology in two different combinations {reference standards}. The study was conducted in two phases: in Phase 2, a modification was made to the LARA that improved the removal of water vapour from the breath sample. RESULTS: In Phase I, data from 331 patients were analysed using a cut off of (delta) 7.8 +/- 0.8, the sensitivity of the method was 91.7% and the specificity was 86.5%, using the reference standard of 2 of 3 tests (CLO, culture or histology) being positive. Positive and negative predictive values were, respectively, 85.2% and 92.5%. In Phase 2 of the study, 160 patients were enrolled and 141 patients were analysed using the same standards. We used the same reference standards but with a cut off of (delta) 6.1 +/- 0.6. The sensitivity and specificity increased to 96.8% and 98.6%, respectively. Positive and negative predictive values were, respectively, 98.4% and 97.3%. The detection rates for H. pylori were similar in patients with peptic ulcer or H. pylori associated gastritis. CONCLUSIONS: The LARA provides an accurate non-invasive means of detecting 13CO2 in the 13C-urea breath test for H. pylori in a multicentre clinical environment that compares well with invasive 'gold standard' methods.

Adolescent↗
PubMed1999

Regional leptin kinetics in humans.

BACKGROUND: Leptin is known to be cleared by the kidney, a tissue with substantial leptin receptor mRNA expression; however, lung, liver, and muscle tissues also express leptin receptor messenger RNA and it is not known whether these tissues also clear leptin from the circulation. OBJECTIVE: This study was conducted to determine whether net leptin clearance takes place in the pulmonary, splanchnic, and leg tissue beds to a similar extent as in the kidney. DESIGN: Plasma leptin concentrations were measured in blood entering and exiting the renal bed, pulmonary bed, splanchnic bed, and leg in 4 groups of subjects. Regional plasma flow was measured in 3 of the 4 groups. RESULTS: Renal leptin uptake was substantial, whereas no net uptake of leptin by the splanchnic or pulmonary vascular beds was detected; leg tissue was a net leptin producer. Net leptin release by leg tissue, relative to leg adipose tissue mass, was comparable with that reported previously for abdominal subcutaneous adipose tissue. CONCLUSION: These results confirm that the kidney is a significant site of leptin clearance in humans, whereas pulmonary and splanchnic beds are not.

Absorptiometry, Photon↗