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S Klein

Publications and source records attributed to S Klein.

At least 199 records · Page 11Linked to original sources

Effect of exercise on lipolytic sensitivity in endurance-trained athletes.

Studies performed in vitro suggest that an acute bout of exercise increases the lipolytic response to beta-adrenergic stimulation. We evaluated the effect of exercise on lipolytic sensitivity in vivo in five endurance-trained athletes. The rate of appearance (Ra) of glycerol in plasma, an index of whole body lipolysis, was determined during 60 min of epinephrine infusion (0.015 microgram.kg-1.min-1) on two occasions: 1) at basal resting conditions and 2) 90 min after completing 1 h of high-intensity (70% O2 uptake) cycle ergometer exercise. Total glycerol Ra during epinephrine infusion in the basal state (352 +/- 35 mumol.kg-1. 60 min-1) was not significantly different from the value obtained after high-intensity exercise (439 +/- 58 mumol.kg-1. 60 min-1). However, the increase in glycerol Ra above baseline during epinephrine infusion was lower after (30 +/- 16 mumol.kg-1. 60 min-1) than before (148 +/- 28 mumol.kg-1. 60 min-1) exercise because of the high postexercise baseline value (P < 0.05). Mean plasma free fatty acid (FFA) concentration was lower during exercise than during epinephrine infusion despite a greater rate of lipolysis during exercise. The slope of change in plasma FFA with respect to glycerol RA was lower during exercise (0.0171 +/- 0.006) than during epinephrine infusion (0.0835 +/- 0.018) (P < 0.05). We conclude that a single bout of intense exercise does not increase in vivo lipolytic sensitivity to beta-adrenergic stimulation in endurance-trained athletes. In addition, plasma FFA concentration represents the balance between plasma FFA inflow and tissue uptake and cannot be used as an index of lipolytic activity during certain physiological conditions, such as exercise.

Adult↗

Technetium-99m-sestamibi scintimammography of breast lesions: clinical and pathological follow-up.

UNLABELLED: Mammography and physical examination combined have a sensitivity of 85% for the detection of breast carcinoma. Mammography also has a positive predictive value of 15%-30%. The aim of this study was to evaluate the usefulness of scintimammography using 99mTc-sestamibi as a complementary technique to mammography for the detection of breast carcinoma to improve mammography's sensitivity and specificity. METHODS: We studied 100 consecutive patients (mean age 48.3 +/- 10.8 yr) who had 106 lesions warranting biopsy (67 lesions) or fine needle aspiration cytology (FNA) (39 lesions) of the breast. There were 85 palpable and 21 nonpalpable lesions. The size of the lesions on the mammograms were moderate (2.3 +/- 1.8 x 1.9 +/- 1.5 cm). Each patient received 20 mCi 99mTc-sestamibi intravenously. Five and 60 min postinjection, planar breast images in the lateral prone position were obtained. An anterior erect projection was then obtained to visualize the axilla and, if needed, a posterior oblique prone projection. RESULTS: Scintimammography was true-positive in 30 lesions with biopsy-confirmed breast carcinoma; it was true-negative in 65 lesions subsequently proved to be benign. There were nine breast lesions with benign findings in which the scintimammography result was positive (false-positive scintimammography) for cancer. Finally, two lesions with pathologically proven carcinomas demonstrated a negative scintimammographic result. Therefore, in this group, the sensitivity of scintimammography was 93.7% with a specificity of 87.8%; the positive predictive value was 76.9%. The negative predictive value was 97%. CONCLUSION: Scintimammography is a highly sensitive test that improves the specificity of conventional mammography for the detection of breast carcinoma.

Biopsy, Needle↗

Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures.

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA-5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.

Antibodies, Monoclonal↗

Polyamines prevent DFMO-mediated inhibition of angiogenesis.

Tumor growth mainly depend on formation of new blood vessels. DFMO (alpha-difluoromethylornithine), an inhibitor of polyamine biosynthesis, inhibits tumor growth in many animal tumors. Our investigation was to evaluate the requirement of polyamines for induction of angiogenesis by tumor cells and spleen lymphocytes from tumor-bearing mice. In this regard, we have added DFMO to cell cultures. The neovascular response induced either by tumor cells or spleen lymphocytes was completely abrogated. This inhibition could be reversed by the addition of exogenous putrescine. These findings suggest that the effect of DFMO on angiogenesis is, in part, mediated by the inhibition of polyamine biosynthesis.

Adenocarcinoma↗

Gallstone pancreatitis. The role of preoperative endoscopic retrograde cholangiopancreatography.

OBJECTIVES: To evaluate the efficacy of endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy in patients with gallstone pancreatitis and to determine criteria predictive of common bile duct stones (CBDS). DESIGN: Retrospective chart review. PATIENTS: Seventy-one consecutive patients with gallstone pancreatitis. MAIN OUTCOME MEASURES: Identification and endoscopic management of CBDS, complications, and mortality. RESULTS: Preoperatively, ERCP revealed CBDS in seven of 22 patients and postoperatively, in five of six patients. All stones were successfully removed. Laboratory values and common bile duct dilatation on admission did not predict CBDS. Persistent hyperamylasemia (> 150 U/L) and persistent hyperbilirubinemia (> 29.07 mumol/L [1.7 mg/dL]) were associated with CBDS on ERCP or intraoperative cholangiography. All five patients with cholangitis underwent ERCP, and CBDS were found and removed in four. There were no deaths and there was a 7% complication rate. CONCLUSIONS: Gallstone pancreatitis can be effectively managed by selective ERCP, endoscopic sphincterotomy, and laparoscopic cholecystectomy. Preoperative ERCP can be restricted to patients with cholangitis, persistent hyperbilirubinemia, or persistent hyperamylasemia.

Adolescent↗

Choose your partner: chromosome pairing in yeast meiosis.

Premeiotic association of homologous chromosomes in the yeast, Saccharomyces cerevisiae has been shown, by means of fluorescent in situ hybridization (FISH). Time course and mutant studies show that the premeiotic associations are disrupted upon entry into meiosis, to be reestablished shortly before synapsis. The data are consistent with a model in which multiple, unstable interactions bring homologues together, prior to stable joining by recombination.

Chromosomes, Fungal↗

Studies on FGF-2: nuclear localization and function of high molecular weight forms and receptor binding in the absence of heparin.

Multiple forms of FGF-2 have been shown to exist in many cell types. These different species of molecular masses of 18, 21.5, 22, and 24 kDa are all translated via the use of alternate initiation codons. The three forms of HMW FGF-2 initiate at CUGs codons, whereas the 18 kDa form initiates at an AUG codon. The entire 18 kDa sequence is contained within the larger forms of HMW FGF-2 as the AUG codon is 3' to the CUG codons. Although the 18 kDa form FGF-2 is localized primarily in the cytosol, a significant fraction of the HMW FGF-2 has a nuclear location. The nuclear localization of HMW FGF-2 is determined by amino acid residues in the amino-terminal extended sequence. The residues required for nuclear localization appear to be RG repeats that are found at multiple sites within the amino-terminal extension of HMW FGF-2. The nuclear localization of HMW FGF-2 suggested that these species may have unique properties. By selecting permanent transfectants of 3T3 cells expressing HMW, 18 kDa FGF-2, or all forms of FGF-2, we have found that HMW FGF-2 can endow cells with a phenotype different from that of cells expressing 18 kDa FGF-2. These cells are transformed by what appears to be the intracellular action of HMW FGF-2. The interaction of FGF-2 with heparin has also been examined.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

2D and 3D high resolution gradient echo functional imaging of the brain: venous contributions to signal in motor cortex studies.

Recent emphasis on high resolution gradient echo studies in functional imaging has led to the conclusion that there are likely three domains of response to the blood circulation in the brain when considering field inhomogeneity effects of the venous blood pre- and during activation. The first is a coherent effect due to large or macroscopic vessels on the order of the size of the voxel (ca 200-500 microns in most studies). These can lead to very large signal changes (up to 100%). The second is at the venule level (ca 50-200 microns) and is associated with smaller parenchymal changes (usually ca 10% or less). The third is at the capillary level and is associated with much smaller signal changes at 1.5 T and even up to 4 T. The actual signal changes depend on field strength and sequence design. In this paper, we present our experience in detecting the first two domains with 2D and 3D gradient echo imaging at 1.5 T. We find that high resolution enables visualization of the larger small veins in motor cortex studies and that, on occasion, it is possible to see the venule effects as well. We suggest a simple model to explain the large signal changes based on susceptibility changes and partial volume effects. Comparisons of the functional imaging data to this model and to MR angiographic studies are also shown as evidence of the venous sources of the susceptibility changes.

Brain↗

Inhibition of class switch recombination in plasma cells.

We investigated whether the absence of class switch recombination in plasma cells is due to the lack of factors required for class switching or to an inhibitor of the recombination present in these cells. Polyclonally activated B cells, actively performing class switch recombination, were fused with IgM-producing PC140 hybridoma cells, i.e., transformed plasma cells, which are capable of undergoing spontaneous class switching, although at low frequency (10(-5)). The switch regions S mu and S gamma 1 are in germline configuration and the genes are demethylated as required for accessibility. In the hybrid-hybridomas the frequency of class switch recombination is not enhanced for PC140 IgH loci but rather inhibited for the IgH loci of the LPS blasts. Thus, fusion of class-switch-performing B cells with the higher differentiated plasma cells, which no longer switch, results in a shutdown of class switching. This points to an inhibitor of the class switch recombination present in plasma cells.

Animals↗

Use of oligonucleotides containing ethenoadenine to study the repair of this DNA lesion. Determination of individual and collective repair activities.

Oligonucleotide duplexes of a defined sequence containing one 1,N6-ethenoadenosine (EA) were synthesized and used as substrates to study the repair of this DNA lesion in cell homogenates of peripheral mononuclear blood cells of 39 male and female workers, exposed to vinyl chloride. These data were compared to data from 39 employees of the same company working in other production plants and to data from a control group of 39 persons, living in an area without vinyl chloride production. After incubation of the 5'- and 3'-labeled oligonucleotide duplex with cell homogenate, a specific nicking activity, releasing the deoxyribosyl phosphate originally carrying the EA, was found. This activity was used to determine the individual and collective repair activities for ethenoadenine. The exposed group showed a mean of 158.5 +/- 39.9 (SD) fmol product fragment and did not differ significantly from the mean value of the two control groups with 156.5 +/- 42.9 fmol and 161.2 +/- 53.6 fmol, respectively. Large interindividual variations were found, ranging from 4.9-fold in the exposed to 8.2- and 7.2-fold in the control groups. The development of an assay for ethenoadenine repair is significant for understanding the role of EA repair in eukaryotic cells.

Adenine↗

Complications of therapeutic laparoscopy.

Laparoscopic surgery holds great promise as a technique for reducing hospital stay and convalescence. Although advantages in hospital cost cannot be shown for all such procedures, improvements in technique and operator experience will undoubtedly improve the situation. Analysis of the pertinent physiologic aspects and complication rates indicates that laparoscopy is not minimally invasive, but rather exposes the patient to many of the risks normally incurred by open procedures. Enthusiasm for the use of these techniques must be tempered by good judgment and scientific evidence supporting equivalent or better long-term results at equal or lower rates of morbidity and mortality.

Appendectomy↗

Protozoa as model systems for the study of cellular responses to altered gravity conditions.

The orientation behavior of Paramecium changed in a similar way after transition to conditions of free-fall in a sounding rocket and after transition to conditions of simulated weightlessness on a fast rotating clinostat. After a period of residual orientation, Paramecium cells distributed themselves randomly 80 s (120 s) after onset of free-fall (simulated weightlessness). Swimming velocity increased significantly; however, the increase was transient and subsided after 3 min in the rocket experiments, while the velocity remained enhanced even during 2 h of rotation on a fast clinostat. Trichocysts were present and without morphological changes in Paramecium cells which had been exposed to a rocket flight, as well as to fast or slow rotation on a clinostat. Regeneration of the oral apparatus of Stentor and morphogenesis of Eufolliculina proceeded normally on the clinostat. The results demonstrate that the clinostat is a useful tool to simulate the conditions of weightlessness on earth and to detect gravisensitive cellular functions.

Animals↗

24-hour profiles of salivary progesterone.

OBJECTIVES: To assess whether the known pulsatility of P secretion by the corpus luteum, which is detected in blood by P measurements, translates into fluctuations of saliva P concentrations, and to determine how well saliva P measurements reflect plasma P concentration. A second objective was to see whether there is a window in the luteal phase, where P secretion has reached its maximum capacity, but the amplitude is not very accentuated, which would be an ideal time to measure P. DESIGN: Twenty-one ovulatory women were randomly assigned to be studied on day 5, 7, or 8 after the luteinizing hormone surge. Blood samples were drawn every 20 minutes, and saliva samples were obtained hourly over a 24-hour period. Comparison between saliva plasma P was performed, and pulse analysis of plasma P was done. RESULTS: The percent variation of saliva P concentration over a 24-hour period was much higher when compared with the percent variation of plasma P concentration over the same time period (saliva P: 149%; plasma P: 107%). Also, the ratio of saliva to plasma P varied significantly between individuals (range: 0.0050 to 0.0148). A single plasma P concentration (8:00 A.M.) correlated better with the 24-hour mean plasma concentration than the respective single saliva value or the mean of two or three saliva samples (8:00 A.M. and 12:00 P.M.; 8:00 A.M., 12:00 P.M., and 8:00 P.M.). Plasma pulse frequency, mean pulse interval, pulse width, pulse amplitude, and 24-hour mean P level did not differ between the 3 study days. CONCLUSIONS: A single plasma P determination reflects more accurately 24-hour P secretion than repeated saliva P samples measured in the same individual. We could not identify a window in the luteal phase when P measurements are more representative of corpus luteum function.

Adult↗

Use of desflurane during resection of phaeochromocytoma.

A patient underwent elective removal of a phaeochromocytoma producing extremely high plasma concentrations of catecholamines. The new volatile agent, desflurane, was incorporated, in varying concentrations, into the general anaesthetic regimen.

Adrenal Gland Neoplasms↗

Changes in lipolytic sensitivity following repeated epinephrine infusion in humans.

The lipolytic response to epinephrine is increased in lean but not obese subjects during conditions of increased circulating catecholamines such as starvation and critical illness. We evaluated the effect of repeated epinephrine treatment (0.03 micrograms.kg-1.min-1 for 30 min thrice daily) on basal lipolysis and the lipolytic response to epinephrine in lean and obese subjects. Lipolytic rates were determined using [2H5]glycerol during basal conditions and 60 min of epinephrine infusion before and after 6 days of repeated epinephrine treatment. Basal lipolysis and the lipolytic response to epinephrine were higher in obese (2.47 +/- 0.51 mumol.kg-1.min-1 and 106 +/- 21 mumol/kg, respectively) than lean (1.45 +/- 0.15 mumol.kg-1.min-1 and 70 +/- 12 mumol/kg, respectively; P = 0.08 obese vs. lean) subjects. Repeated epinephrine treatment decreased basal glycerol rate of appearance and the lipolytic response to epinephrine in lean and obese subjects. Plasma insulin concentration increased after repeated epinephrine treatment in both obese (14.3 +/- 0.6 to 18.2 +/- 1.6 microU/ml; P < 0.05) and lean (8.4 +/- 1.3 to 11.1 +/- 1.5 microU/ml; P < 0.01) subjects. Repeated epinephrine treatment suppresses basal and epinephrine-stimulated lipolysis. Increased plasma insulin concentration may be the mechanism.

Adult↗

Fat metabolism during low-intensity exercise in endurance-trained and untrained men.

Whole body lipid kinetics were evaluated during basal resting conditions, 4 h of treadmill exercise eliciting an oxygen uptake of 20 ml.kg-1.min-1, and 1 h of recovery in five untrained and five endurance-trained men. Glycerol and free fatty acid (FFA) rate of appearance (Ra) values in plasma were determined by infusing [2H5]glycerol and [1-13C]palmitate, respectively, and lipid oxidation was determined by indirect calorimetry. The lipolytic response to 4 h of exercise, expressed as the average glycerol and FFA Ra values, was similar in both trained (9.85 +/- 1.02 and 24.64 +/- 3.76 mumol.kg-1.min-1, respectively) and untrained subjects (11.29 +/- 0.99 and 24.13 +/- 0.39 mumol.kg-1.min-1, respectively). However, mean triglyceride oxidation was greater during exercise in the trained than in the untrained group (7.51 +/- 0.26 and 5.67 +/- 0.51 mumol.kg-1.min-1, respectively; P < 0.001). During recovery, glycerol and FFA Ra values decreased more rapidly in trained than in untrained subjects. We conclude that highly trained male endurance runners use more fat as a fuel during low-intensity exercise than do untrained healthy men despite similar rates of lipolysis and FFA uptake from plasma. Therefore, the increase in fat oxidation must be related to an increased percentage of FFA uptake oxidized, a greater contribution from intramuscular triglyceride stores, or both. Additionally, lipid kinetics return to baseline more rapidly in trained than in untrained subjects after completing an exercise bout of the same absolute intensity.

Adult↗