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Biomedical subjects

S Klein

Publications and source records attributed to S Klein.

At least 325 records · Page 18Linked to original sources

The use of isotopic tracers in studying lipid metabolism in human subjects.

We have attempted to evaluate some of the tracer methodologies involved in studying lipid metabolism in humans. The magnitude of this subject prohibits a comprehensive review of all areas. Since the major function of adipose tissue appears to be to supply the body with energy, we have particularly emphasized the approaches used to study the mobilization and oxidation of fat. The importance of these issues, as well as the increasing availability of non-radioactive tracers, suggest an optimistic future for this area of research.

Absorption↗

Duodenal fistulas in Crohn's disease.

Of 1,480 patients with Crohn's disease admitted to The Mount Sinai Hospital between 1960 and 1983, eight (0.5%) had duodenal fistulas (DF), all originating from diseased small or large bowel and not from primary disease of the duodenum. The extent, duration, and major clinical features of Crohn's disease did not differ between patients with DF and those with other fistulas. Six of the patients underwent surgery for refractory disease or abscess formation and two patients were treated medically. All improved and were able to maintain an adequate oral intake after treatment. At follow-up 3-10 years later, the surgically treated patients were well but both medically treated patients had died, one from a probably unrelated brain tumor 7 years after discharge and one from necrotizing pancreatitis 10 years later. Our experience suggests that the presence of a DF is not an absolute indication for early surgery. The initial therapeutic management of such patients should be determined by the nature and severity of the underlying Crohn's disease rather than the presence of a DF. The late pancreatic complication in a patient with a chronic DF, however, raises the question of an association between the two.

Adult↗

Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects.

In this study the rate of lipolysis (fatty acid and glycerol release into blood) has been quantified in both normal weight and obese volunteers after both 15 and 87 h of fasting. In each study, the basal rate and subsequent response to epinephrine infusion (0.015 microgram X kg-1 X min-1) were determined. The rate of appearance (Ra) of free fatty acids (FFA) and glycerol were quantified by infusion of [1-13C]palmitate and D-5-glycerol, respectively. Substrate flux rates per unit of body fat mass and lean body mass were calculated from total body water measurements using H2(18)O dilution. In normal volunteers, the basal Ra FFA and Ra glycerol rose markedly with 87 h of fasting, whereas the increases were more modest in the obese subjects. However, the rate of mobilization of fat, in relation to the lean body mass, was higher in the obese subjects than in the normal subjects after 15 h of fasting, and the values were similar in both groups after 87 h of fasting. There was an increased lipolytic response to epinephrine after fasting in both groups. This increased sensitivity may have resulted from the enhancement of fatty acid-triglyceride substrate cycling that occurred after fasting.

Adult↗

Total parenteral nutrition and cancer clinical trials.

Twenty-eight prospective randomized controlled clinical trials evaluating the use of total parenteral nutrition (TPN) in cancer patients were identified through a search of major indexing sources. The data were pooled across studies to increase the ability to detect therapeutic effects. The impact of publication bias and the quality of reporting each trial were used to critically assess the conclusions drawn from the pooled analysis. The authors conclude that TPN may be useful when used preoperatively in patients with gastrointestinal tract cancer. It appears to be beneficial in reducing major surgical complications (pooled P = 0.01) and operative mortality (pooled P = 0.02). No statistically significant benefit from TPN could be demonstrated in survival, treatment tolerance, treatment toxicity, or tumor response in patients receiving chemotherapy or radiotherapy. An increase in the risk of developing an infection in chemotherapy patients given TPN (pooled P less than 0.0001) underscores the importance of demonstrating significant benefits in randomized trials before TPN is used routinely in these patients.

Clinical Trials as Topic↗

Relation of serum reverse T3 to amiodarone antiarrhythmic efficacy and toxicity.

The relation of serum reverse T3 (rT3) to amiodarone efficacy and toxicity was studied in 31 patients with frequent and complex ventricular arrhythmias. Baseline studies included 48-hour Holter recordings and rT3 levels (normal 33 ng/dl or less). Amiodarone therapy was initiated with a 5 mg/kg infusion followed by 600 to 800 mg/day for 7 to 10 days, then 200 to 400 mg/day. Holters and rT3 levels were repeated every 1 to 3 months and amiodarone was titrated to achieve at least a 70% reduction in total ventricular premature complexes, at least a 90% reduction in couplets and abolition of ventricular tachycardia. The baseline rT3 level was 18 +/- 7 ng/dl (range 10 to 30) and patients were followed 12 +/- 9 months. Arrhythmia control was achieved in 25 patients (81%), including 21 patients with elevated rT3 levels (36 to 105 ng/dl) and 4 patients with normal rT3 (15 to 33 ng/dl). Six patients were uncontrolled with rT3 (27 to 90 ng/dl) and 14 patients had minor side effects with rT3 (27 to 123 ng/dl). Three of 4 patients in whom rT3 levels exceeded 130 ng/dl died suddenly (137 to 174 ng/dl before the event). Thus, amiodarone efficacy and minor toxicity occurs at rT3 levels less than 105 ng/dl and sudden death may be associated with levels greater than 130 ng/dl.

Aged↗

[Epidemiology, clinical aspects and follow-up of diabetic retinopathy in type II diabetes mellitus].

In 960 30- to 50-year-old patients with purely dietetically manageable, newly detected Type II diabetes, the fundus of the eye was kept under observation for 5 years. The prevalence of diabetic retinopathy was 58.6% (45.6% preretinopathy, 13% retinopathy) in the first year and 91% (78% preretinopathy, 13% retinopathy) after 5 years. The clinical picture of the fundus in Type II diabetes is characterized by arteriosclerotic changes and a mild diabetic retinopathy with only slow progression.

Adult↗

Control of immunoglobulin class switch recombination.

The comparative analysis of Ig class switch recombination in a priori IgG/IgA-expressing myelomas and hybridomas, in switch variants and in activated normal B cells shows the following characteristics of class switch recombination in activated B cells: It is prevented during most of B cell ontogeny. It happens on both IgH loci of activated and switched B cells. The recombination is programmed in that on both IgH loci of switched cells the same switch regions recombine with Smu. This is true at least for the IgG1 pathway. IgM-expressing cells show no class switch recombination on the inactive IgH locus. Thus, physiological class switch recombination is a programmed rather than a random event and is controlled as such. The initial stages of class switching and the molecules involved in these are largely unclear: What is the nature of the protection of switch regions and how is this protection abrogated? Do specific recombinases exist? What is the role of large transcription units? Is the specificity of class switch recombination a result of specific "opening" of the DNA for transcription? Do all B cells use the same switch mechanism? What is the role of switch factors (such as lymphokines)? These and more questions await answers and although a variety of switch scenarios could be discussed at present a detailed speculation seems premature.

Animals↗

Graft-vs-host reaction induced by para-aortic lymph nodes during estrous and diestrous stages.

Mouse uterine draining lymph node (UDLN) cells, or soluble factors released by them in both phases of the estrous cycle were examined in the graft-vs-host (GVH) assay. The immune response during the estrous phase was significantly decreased as compared with diestrous phase; 24-hour culture supernatant of UDLN cells was also able to decrease GVH activity mounted in F1 hybrids. This difference in reactivity was not found when peripheral nodes (PN) or spleen cells were tested. These results show that in physiological conditions it is possible to detect an hormonal influence on T lymphocyte function and would suggest that a non-specific immunosuppression would appear even during the estrous phase.

Animals↗

Long-term treatment of tumor-operated mice with high doses of alpha-difluoromethylornithine.

Mice inoculated subcutaneously with a mammary adenocarcinoma M3cell suspension and submitted 10 to 15 days later to the surgical removal of primary tumors have been chosen in our laboratory as the experimental model to study the effect of several drugs on metastasis spreading. A 90-day treatment of tumor-operated mice with high doses of alpha-difluoromethylornithine showed, in addition to a marked decrease of lung metastases, several side effects including a loss of body weight, a delay of surgical wound healing and a reduced number of megakaryocytes in bone marrow. The measurement of ceruloplasmin in serum has indicated that treated animals contained increased levels of this oxidase activity in spite of the polyamine depletion caused by alpha-difluoromethylornithine. These results rule out a direct correlation between ceruloplasmin activity and polyamine concentration.

Adenocarcinoma↗

Palmitate and glycerol kinetics during brief starvation in normal weight young adult and elderly subjects.

Data obtained in vitro suggest that the ability to mobilize fat decreases with age. We determined lipolytic rates in vivo in normal weight young adult (22-33 yr) and elderly (65-77 yr) subjects using a simultaneous infusion of [1,2-13C2]palmitate and [2H5]glycerol. The subjects were studied after a 12-h fast and again after 60-82 h of fasting. When lipolysis was expressed per unit of adipose tissue the values for the young adults were more than double those for the elderly (P less than 0.05). However, the amount of body fat in the elderly was twice that of the young adults, so that lipolysis per unit of body weight was similar in both groups. These results demonstrate that lipolysis per unit of adipose tissue is lower in elderly subjects. This may be due to their increase in body fat, however, since the total amount of potential energy mobilized from adipose tissue was similar to that of the young adults.

Adipose Tissue↗

Evidence for transient requirement of the IgH enhancer.

A transcriptional enhancer is thought to play a major role in determining tissue-specific expression of the immunoglobulin heavy chain (IgH) gene (1-3). However in three B-lymphoid cell lines the Ig enhancer has been lost due to a spontaneous deletion, yet heavy chain synthesis persists at a high level (4-6). In the case of the enhancerless delta chain gene (5) we wanted to test whether the IgH enhancer is no longer necessary for maintenance of transcription or whether perhaps a new enhancer was created de novo by the deletion process. To this end we have cloned the relevant portion of the variant IgH gene and transfected it into myeloma and hybridoma cells. We find that the reintroduced gene segment is not expressed unless it is linked again to an enhancer. The results suggest that the IgH enhancer is necessary for the onset of transcription, presumably by organizing the gene into stable transcription complexes, but is dispensable at later stages once the transcription unit is activated.

Animals↗

[Comparative studies of 2 organic mercury compounds alone or in combination with ethanol following pre- or postnatal application in mice].

Studies on pre- and/or postnatal effects on mice were carried out with their identical exposure (2 mg Hg/kg body mass) to phenyl mercuric acetate or N,N'-bis-(dimethylmercury)-p-toluol-sulphonamide. Parameters of morphology, of residues, and behaviour teratology were taken into consideration. Potentiating combination effects were only observed with behaviour toxicological investigations after prenatal exposure to methylmercury. That concerned the breeding results of the P-generation and the capacity of the F1-generation to learn on the 30th and 31st day p.n. during a swimming test in a labyrinth. Synergistic effects were observed with both the mercury compounds in the swimming test on the 12th day p.n. after pre- as well as postnatal exposure.

Animals↗

Stereo-deficients and stereoblinds cannot make utrocular discriminations.

In two separate experiments, we show that stereo-deficient observers are no better than stereonormals at discriminating the eye-of-origin of a monocular stimulation. Stereo-deficient observers are considered to have a preponderance of monocular neurons throughout their visual system, including the visual cortex. The results indicate that, in spite of their clear anatomical and physiological structure, such monocular neurons do not convey eye-of-origin information to consciousness.

Depth Perception↗

[Value of iris fluorescence angiography in the early diagnosis of vascular lesions].

Fluorescein angiographies of the iris and retina were performed both in normal individuals (104) and in patients suffering from hyperlipoproteinemia (48), maturity-onset diabetes (184), systemic hypertension (12) and atherosclerosis (12). While hyperpermeation of dye located at the pupillary border was seen in 7.7% of the normals, leakages occurred in 66.6% of the hyperlipoproteinemics and in 79% of the recent maturity-onset diabetics. Paraclinical examination of the normal subjects with pathologic dye transit revealed vascular risk factors in each case. Thus, fluorescein iris angiography is a suitable method of detecting vascular damage in cases of metabolic disorder as early as possible.

Adolescent↗

Effect of alpha-difluoromethylornithine in lung metastases before and after surgery of primary adenocarcinoma tumors in mice.

The depletion of polyamines by alpha-difluoromethylornithine (DFMO) treatment of mice after subcutaneous inoculation of adenocarcinoma M3 cells caused a remarkable inhibition in the growth rate of primary tumors as well as in the occurrence and number of lung metastases with a concomitant increase in survival time. Tumor-bearing mice submitted to the surgical removal of primary tumors and then treated with alpha-difluoromethylornithine also showed a significant reduction of lung metastases. In addition, a lower number of lung metastatic nodules correlated with decreased levels of polyamines in the same tissue. The described approach provides a useful experimental model for studies in human cancer therapy.

Adenocarcinoma↗