Search PubMed⌕ Search

Biomedical subjects

S Klein

Publications and source records attributed to S Klein.

At least 19 recordsLinked to original sources
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

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

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↗
PubMed1999

Effect of short-term fasting on lipid kinetics in lean and obese women.

We evaluated whole body and regional adipose tissue lipid kinetics and norepinephrine (NE) spillover during brief fasting in six lean [body mass index (BMI) 21 +/- 1 kg/m2] and six upper-body obese (UBO; BMI 36 +/- 1 kg/m2) women. At 14 h of fasting, abdominal adipose tissue glycerol and free fatty acid (FFA) release rates were lower (P = 0.07), but whole body glycerol and FFA rates of appearance (Ra) were greater (P < 0.05) in obese than in lean subjects. At 22 h of fasting, glycerol and FFA Ra increased less in obese (19.8 +/- 7.0 and 87.1 +/- 30.3 micromol/min, respectively) than in lean (44.2 +/- 6.6 and 137.4 +/- 30.4 micromol/min, respectively; P < 0.05) women. The percent increase in glycerol Ra correlated closely with the percent decline in plasma insulin in both groups (r2 = 0.85; P < 0.05). Whole body NE spillover declined in lean (P < 0.05) but not obese subjects with continued fasting, whereas regional adipose tissue NE spillover did not change in either group. We conclude that, compared with lean women, in UBO women 1) basal adipose tissue lipolysis is lower, but whole body lipid kinetics is higher because of their greater fat mass; 2) the increase in lipolysis during fasting is blunted because of an attenuated decline in circulating insulin; and 3) downregulation of whole body sympathetic nervous system activity is impaired during fasting.

Adipose Tissue↗
PubMed1998

Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression.

An increased expression of nitric oxide synthase (NOS) has been observed in human colon carcinoma cell lines as well as in human gynecological, breast, and central nervous system tumors. This observation suggests a pathobiological role of tumor-associated NO production. Hence, we investigated NOS expression in human colon cancer in respect to tumor staging, NOS-expressing cell type(s), nitrotyrosine formation, inflammation, and vascular endothelial growth factor expression. Ca2+-dependent NOS activity was found in normal colon and in tumors but was significantly decreased in adenomas (P < 0.001) and carcinomas (Dukes' stages A-D: P < 0.002). Ca2+-independent NOS activity, indicating inducible NOS (NOS2), is markedly expressed in approximately 60% of human colon adenomas (P < 0.001 versus normal tissues) and in 20-25% of colon carcinomas (P < 0.01 versus normal tissues). Only low levels were found in the surrounding normal tissue. NOS2 activity decreased with increasing tumor stage (Dukes' A-D) and was lowest in colon metastases to liver and lung. NOS2 was detected in tissue mononuclear cells (TMCs), endothelium, and tumor epithelium. There was a statistically significant correlation between NOS2 enzymatic activity and the level of NOS2 protein detected by immunohistochemistry (P < 0.01). Western blot analysis of tumor extracts with Ca2+-independent NOS activity showed up to three distinct NOS2 protein bands at Mr 125,000-Mr 138,000. The same protein bands were heavily tyrosine-phosphorylated in some tumor tissues. TMCs, but not the tumor epithelium, were immunopositive using a polyclonal anti-nitrotyrosine antibody. However, only a subset of the NOS2-expressing TMCs stained positively for 3-nitrotyrosine, which is a marker for peroxynitrite formation. Furthermore, vascular endothelial growth factor expression was detected in adenomas expressing NOS2. These data are consistent with the hypothesis that excessive NO production by NOS2 may contribute to the pathogenesis of colon cancer progression at the transition of colon adenoma to carcinoma in situ.

Adenoma↗
PubMed1998

[Success and failure in laparoscopic "gastric banding". A report of 3 years experience].

During 3 years, the adjustable gastric band (AGSB) was laparoscopically implanted in 224 of 873 patients with morbid obesity. The operation was done by 7 surgeons. Problems arising from the operative technique are: early pouch dilatation, gastric slippage, gastric perforation, penetration of the band, port infection, penetration of the port, defect of the band catheter. These can be avoided by care and increasing experience. The late pouch dilatation and the insufficient loss of excess weight arise from the unsatisfactory compliance of the patient. Critical selection of patients is necessary. Total morbidity in this seria was 19%, the letality 0.4% and the average excess weight loss within 2 years was 50 +/- 28%. The results may be improved by restrictive selection of patients and great operative routine.

Adult↗
PubMed1998

Metabolic alteration in patients with cancer: nutritional implications.

During the past 20 years, efforts have been made to elucidate the metabolic changes observed in patients with cancer by using stable and radioactive isotopic tracers. These metabolic changes in patients with cancer may be similar to those in other stress conditions, in which glucose production and utilization, lipolysis and free fatty acid flux, and net protein catabolism are increased. Stress hormones, such as glucagon and catecholamines, and certain cytokines may be responsible for these metabolic changes. Although it has been shown that cachexia in patients with cancer signals a poor prognosis, efforts to improve the clinical outcomes with nutritional support have been disappointing. The failure of cancer patients to respond to nutritional support may be related to an alteration in the intermediate metabolism. Therefore, further research evaluating the metabolic abnormalities associated with cancer may lead to more effective nutritional therapies.

Cachexia↗
PubMed1998

Improved accuracy and precision of gas chromatography/mass spectrometry measurements for metabolic tracers.

The use of stable-isotope tracer methodology to study substrate metabolic kinetics requires accurate measurement of the tracer to tracee ratio (TTR), often by gas chromatography/mass spectrometry (GC/MS). Many approaches for measurement of the TTR by GC/MS do not use standards of known isotopic enrichment to control for variability in instrument response. In addition, most GC/MS applications exhibit some degree of concentration dependency whereby the measured ion abundance ratio varies with the quantity of sample analyzed, thereby placing a limitation on the accuracy of isotopic enrichment standard curves unless the quantities of standards and samples analyzed are closely matched. We document the degree to which day-to-day variability can affect the instrument response for several GC/MS analyses of metabolic tracers when isotopic enrichment standards are not used to control for variable instrument response. Furthermore, we report a new approach that incorporates concentration dependencies within a standard curve to improve the accuracy and precision of TTR measurements over a range of sample quantities analyzed. The new approach was applied to plasma samples obtained from experimental protocols performed in human subjects with three commonly used tracers: 2H2-palmitate, 15N2-urea, and 13C-leucine. Variability in the day-to-day instrument response was 84% and 26% for 2H2-palmitate and 15N2-urea, respectively; in addition, up to 10% variability due to concentration dependency was noted for these applications. The new approach virtually eliminated these sources of variability. After controlling for concentration dependency, a threefold reduction in the standard error was noted when the enrichment of 13C-leucine measured by electron-impact (EI) ionization GC/MS was correlated against negative chemical ionization (NCI) GC/MS. These data demonstrate that our new approach decreases the errors in TTR determination caused by variations in instrument response and concentration dependency. This approach is generically applicable, and can improve the accuracy and precision of TTR determinations for most GC/MS analyses.

Adolescent↗
PubMed1998

High-flux dialysis lowers plasma leptin concentration in chronic dialysis patients.

Leptin is a protein produced by fat cells and involved in body weight regulation. Plasma leptin is significantly higher in some hemodialysis (HD) patients than in normal controls. We examined the influence of dialyzer membrane biocompatibility and flux on elevated plasma leptin concentrations in hemodialysis patients. Employing a crossover design, leptin and tumor necrosis factor-alpha (TNF-alpha) levels were serially determined in eight chronic dialysis patients. Patients were dialyzed sequentially on low-flux cellulosic (TAF) dialyzers, low-flux (F8) polysulfone, high-flux (F80B) polysulfone, then low-flux polysulfone and cellulosic dialyzers again. Mean leptin concentrations were similar when low-flux polysulfone or cellulosic dialyzers were employed (141.9+/-24.2 microg/L versus 137.8+/-18.4 microg/L, respectively (P=NS). In contrast, leptin fell significantly on the high-flux polysulfone dialyzer (99.4+/-16.2 microg/L) compared with cellulosic (P < 0.005), and low-flux polysulfone dialyzers (P < 0.02). Leptin clearance by the high-flux polysulfone dialyzer was significantly higher than the low-flux dialyzers (50.4+/-21.5 v -9.6+/-10.3 mL/min; P=0.043), but did not account fully for the 30% decline in plasma leptin during the high-flux arm of the study. Concentrations of TNF-alpha were lower when high-flux polysulfone dialyzers were employed, but there was no correlation of individual TNF-alpha levels with leptin concentrations. High-flux dialysis lowers plasma leptin concentrations an average of 30%, but biocompatibility does not influence leptin levels. The decrease in plasma leptin on high-flux dialysis cannot be explained solely by enhanced clearance.

Cross-Over Studies↗
PubMed1998

Effective reversal of a transformed phenotype by retrovirus-mediated transfer of a ribozyme directed against mutant N-ras.

A hammerhead ribozyme directed against oncogenic N-ras (N13-ras) was introduced into a retroviral vector and its activity evaluated in vitro and in cell lines. The catalytic efficiency of the ribozyme embedded within a 2618 nucleotides in vitro-generated transcript was not significantly affected by the length of non-base pairing flanking sequences. A sensitive assay based on N-ras/luciferase fusion transcripts as a reporter system was used to assess ribozyme activity in mammalian cells. More than 95% reduction in luciferase activity was observed in cells transduced with a retrovirus containing the active form of the ribozyme, whereas no significant reduction was observed with the inactive form of the same ribozyme. In order to assay the activity of the retrovirally encoded ribozyme in a biological setting, the IL-3-dependent cell line TF-1 was transformed with N13-ras. Expression of N13-ras in these cells induced factor-independent colony growth and a dose-dependent proliferative response to erythropoietin (Epo). Retrovirus-mediated expression of the active form of the ribozyme in these cells restored factor-dependent colony growth and abolished the proliferative response to Epo. The reversion of the transformed phenotype correlated with a reduction in the amount of N13-ras mRNA.

Animals↗
PubMed1998

A questionnaire-based outcome analysis of the Stamey bladder neck suspension procedure for the treatment of urinary stress incontinence: the Hannover experience.

OBJECTIVES: To evaluate the long-term continence rate, including subjective satisfaction and therapy-associated morbidity, of patients undergoing Stamey bladder neck suspension. PATIENTS AND METHODS: Eighty-five women (median age 55 years, range 30-85) with urinary stress incontinence treated by Stamey bladder neck suspension at our institution between 1987 and 1995 were evaluated using an anonymous questionnaire over a mean (range) follow-up of 61 (13-93) months. RESULTS: Of the 85 patients, 44 (52%) reported an improvement in clinical symptoms at the evaluation and 29 (34%) were completely continent after the Stamey procedure. However, 53 (62%) patients reported subjective satisfaction with the result, because they had a durable improvement in continence for a mean (range) of 44 (10-79) months. There was no correlation between the number of previous urogynaecological operations undergone by the patients and the success of the Stamey procedure. However, the frequency of complications other than urinary retention was significant during and after surgery, at 27%, and in accord with the complication rate reported in earlier studies. CONCLUSIONS: Compared with other bladder neck suspension procedures, e.g. Burch colposuspension, the Stamey procedure appears to be associated with a higher frequency of postoperative recurrent urinary stress incontinence. Therefore, the Stamey procedure should only be used if the patient demands a minimally invasive surgical procedure for bladder neck suspension. Although approximately equal to 60% of patients were satisfied with the durable improvement in clinical symptoms, it is appropriate to inform patients before surgery of the high recurrence rate after Stamey bladder neck suspension.

Adult↗
PubMed1998

Alternative strategies of opiate detoxification: evaluation of the so-called ultra-rapid detoxification.

This study was done in order to examine the hypothesis that so-called ultra-rapid opiate detoxification provides a mild, short, and safe withdrawal. A total of 22 patients who were addicted to opiates exclusively underwent ultra-rapid detoxification. Each patient was pretreated with methadone. During general anesthesia lasting about six hours with methohexital or propofol, naloxone was administered with doubling of the dose every 15 minutes with a starting bolus dose of 0.4 mg. The total bolus dose of 12.4 mg, delivered within 60 minutes, was followed by a naloxone infusion of 0.8 mg/h until the next morning. On the day of anesthesia naltrexone (50 mg/d) treatment was initiated. When withdrawal symptoms occurred, specific medications, e.g., clonidine, were added. After determining baseline values, withdrawal symptoms were investigated during a further four weeks by means of established clinical scales. The results document marked withdrawal symptoms for at least one week after detoxification. The intensity of withdrawal symptoms during the first seven days of treatment was significantly (p<0.05) more marked than during baseline. None of the patients underwent a life-threatening complication and only one patient failed to complete the detoxification procedure. Finally, about 75% of the patients could be referred for further treatment. In this study ultra-rapid detoxification provided a safe withdrawal procedure with high rates of completed withdrawals and referrals for further treatment, respectively. However, in contrast to previous reports, many patients suffered from middle-grade withdrawal symptoms over several days. Due to the risks of general anesthesia and the expense associated with this treatment, only patients addicted to opiates alone and for whom other detoxification strategies are unsuitable should undergo a ultra-rapid detoxification procedure.

Adolescent↗
PubMed1998

Analysis of chicken embryonic development after removal of blastodermal cells for sexing.

1. The present study evaluated developmental characteristics in the chick embryo throughout incubation following cell removal from the freshly laid egg. 2. Between 10 and a few hundred cells of the blastoderm were removed for sex diagnosis. Incubation of the treated embryos was then continued in an open egg shell culture system. 3. Cell recovery from different regions within the blastoderm was performed. 4. The experiments presented here demonstrate the persistence of the developmental potential of chicken embryos in an in ovo culture system after removal of different numbers of cells from the germinal disc prior to incubation. 5. No deviations in developmental characteristics were recorded when compared to untreated control cultures. 6. No detrimental effects of double cell biopsies could be observed. 7. A similar number of chicks developed to hatch regardless of the location of manipulation within the blastoderm.

Animals↗
PubMed1998

Clinical nutrition: opportunity in a changing health care environment.

This article summarizes presentations from a satellite symposium, "Clinical Nutrition: Opportunity in a Changing Health Care Environment," held July 26, 1997, at the 37th annual meeting of the American Society for Clinical Nutrition in Montreal. The symposium was cosponsored by the American Society for Clinical Nutrition and the American Society for Parenteral and Enteral Nutrition. The diverse topics served as a practical forum for sharing information on innovative responses, concerns, and impediments in the rapidly evolving practice environment.

Enteral Nutrition↗