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Biomedical subjects

S Larson

Publications and source records attributed to S Larson.

71 records · Page 4Linked to original sources

Regulation of glutamine synthetase and glutaminase activities in cultured skeletal muscle cells.

Glutamine is synthesized in skeletal muscle, released to the circulation, and transported to other tissues, where it may provide important substrate for gluconeogenesis, ammoniagenesis, and energy-yielding pathways. With the ultimate goal of delineating the factors that control glutamine production and release by skeletal muscle, we have studied the regulation of two key enzymes, glutamine synthetase and glutaminase, in the L6 line of rat skeletal muscle cells grown in monolayer culture. The cultured myotubes were found to have glutamine synthetase and phosphate-dependent glutaminase activities. Glutamine synthetase activity was increased following incubation (1) in glutamine-free medium (threefold); (2) in medium containing high glutamic acid concentrations (fourfold); and (3) in medium supplemented with dexamethasone (threefold). In each case the increase in glutamine synthetase activity required several hours to reach a maximum and was prevented by cycloheximide, suggesting that the change occurred through increased enzyme biosynthesis. No substances tested were found to affect glutaminase activity. We conclude that glutamine synthetase in cultured skeletal muscle is responsive to substrate, product, and hormonal regulation.

Animals↗

Effect of electrical current on temperature and pH in cerebellum and spinal cord.

Electrical currents similar to those used for relief of pain and spasticity were applied to the spinal cord and cerebellum of monkeys and cats. Direct coupled monopolar pulses increased pH at the tissue surface near a negative electrode and correspondingly decreased the pH near a positive electrode. Cerebrospinal fluid (CSF) circulation around the electrodes neutralized these changes. Capacitively coupled currents up to a 10 mA peak and 2.5 mucoul per peak failed to change tissue pH measurably. Current levels with power densities of 100 mW per cm2 did not cause any change in tissue temperature.

Animals↗

Acquired resistance to parathyroid hormone.

Studies are presented in a patient with pseudohypoparathyroidism who showed a partial response to parathyroid extract. Resistance to the extract was observed after its short-term administration for the gourth time. Serum from the patient contained antibodies of the gamma G globulin class which bound 125I-labelled bovine parathyroid hormone. Prior incubation of parathyroid hormone with the serum prevented the activation in vitro of adenylate cyclase from pork renal cortex. The antibodies were directed primarily toward the C-terminal portion of the molecule. Thus, clinical resistance to parathyroid hormone is attributed to specific antibodies.

Adenylyl Cyclases↗

Simple radiometric techniques for rapid detection of herpes simplex virus type 1 in WI-38 cell culture.

Two radiometric techniques were developed for detecting the presence of herpes simplex virus type 1 in stationary monolayers of the diploid cell line WI-38. The time of detection was compared to that obtained from visual examination for cytopathic effects in the same cell line. Oxidation of 14C-1-glucose in infected and uninfected cells was determined by 14CO2 production, measured by an ionization chamber, and DNA synthesis was determined by 3H-thymidine incorporation, measured by scintillation counting. Compared to uninfected cells, infected cells showed a 23-26% reduction in 14C-1-glucose oxidation and a 355-498% increase in DNA synthesis 4-6 hr after infection. These changes in cellular metabolism were observed 14 hr before visible signs of cytopathic effects. The increase in DNA synthesis was completely inhibited by viral neutralization with herpes simplex antiserum. Increased DNA synthesis was observed 5 hr after infection with 10,000-3,200,000 TCID50 units of virus. These radiometric methods for the detection of viral effect on cellular metabolism are simple, fast, and objective.

Carbon Radioisotopes↗

Experts practice what they preach: A descriptive study of best and normative practices in end-of-life discussions.

BACKGROUND: Advance directives (ADs) are widely regarded as the best available mechanism to ensure that patients' wishes about medical treatment at the end of life are respected. However, observational studies suggest that these discussions often fail to meet their stated goals. OBJECTIVES: To explore best practices by describing what physicians who are considered expert in the area of end of-life bioethics or medical communication do when discussing ADs with their patients and to explore the ways in which best practices of the expert group might differ in content or style from normative practice derived from primary care physicians' discussions of ADs with their patients collected as part of an earlier study. DESIGN: Nonexperimental, descriptive study of audiotaped discussions. SETTING: Outpatient primary care practices in the United States. PARTICIPANTS: Eighteen internists who have published articles in the areas of bioethics or communication and 48 of their patients. Fifty-six academic internists and 56 of their established patients in 5 practice sites in 2 locations-Durham, NC, and Pittsburgh, Pa. Eligible patients were at least 65 years old or suffered from serious medical illness and had not previously discussed ADs with their physician. Expert clinicians had discretion regarding patient selection, while the internists chose patients according to a predetermined protocol. MEASUREMENTS: Coders applied the Roter Interaction Analysis System (RIAS) to audiotapes of the medical visits to describe communication dynamics. In addition, the audiotapes were scored on 21 items reflecting physician performance in specific skills related to AD discussions. RESULTS: Experts spent close to twice as much time (14.7 vs 8.1 minutes, P<.001) and were less verbally dominant (P<.05) than other physicians during AD discussions. When length of visit was controlled statistically, the expert physicians gave less information about treatment procedures and biomedical issues (P<.05) and asked fewer related questions (P<. 05) but tended toward more psychosocial and lifestyle discussion and questions. Experts engaged in more partnership building (P<.05) with their patients. Patients of the expert physicians engaged in more psychosocial and lifestyle discussion (P<.001), and more positive talk (P<.05) than patients of community physicians. Expert physicians scored higher on the 21 items reflecting AD-specific skills (P<.001). CONCLUSIONS: Best practices as reflected in the performance of expert physicians reflect differences in measures of communication style and in specific AD-related proficiencies. Physician training in ADs must be broad enough to include both of these domains. Arch Intern Med. 2000;160:3477-3485.

Adult↗

Combined spinal-epidural anesthesia for Cesarean section in a patient with peripartum dilated cardiomyopathy.

PURPOSE: To report a case of peripartum dilated cardiomyopathy associated with morbid obesity and possible difficult airway presenting for elective Cesarean section, which was successfully managed with combined spinal-epidural anesthesia. CLINICAL FEATURES: A morbidly obese parturient with a potentially difficult airway, suffering from idiopathic peripartum cardiomyopathy (ejection fraction 20%), was scheduled for an elective Cesarean section. A combined spinal epidural anesthesia was performed and 6 mg of bupivacaine were injected into the subarachnoid space. This was supplemented after 60 min with 25 mg of bupivacaine injected epidurally. The patient's hemodynamic status was monitored with direct intra-arterial blood pressure and central venous pressure measurements. The patient's perioperative course was uneventful. CONCLUSION: In patients suffering from peripartum cardiomyopathy, undergoing Cesarean section, combined spinal-epidural anesthesia may be an acceptable anesthetic alternative.

Adult↗

Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo.

A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, and could elucidate temporal dynamics and immune regulation at different stages of disease and following therapy. We developed and assessed a novel method for monitoring the T-cell receptor (TCR)-dependent nuclear factor of activated T cells (NFAT)-mediated activation of T cells by optical fluorescence imaging (OFI) and positron emission tomography (PET). The herpes simplex virus type 1 thymidine kinase/green fluorescent protein [HSV1-tk/GFP (TKGFP)] dual reporter gene was used to monitor NFAT-mediated transcriptional activation in human Jurkat cells. A recombinant retrovirus bearing the NFAT-TKGFP reporter system was constructed in which the TKGFP reporter gene was placed under control of an artificial cis-acting NFAT-specific enhancer. Transduced Jurkat cells were used to establish subcutaneous infiltrates in nude rats. We demonstrated that noninvasive OFI and nuclear imaging of T-cell activation is feasible using the NFAT-TKGFP reporter system. PET imaging with [(124)I]FIAU using the NFAT-TKGFP reporter system is sufficiently sensitive to detect T-cell activation in vivo. PET images were confirmed by independent measurements of T-cell activation (e.g., CD69) and induction of GFP fluorescence. PET imaging of TCR-induced NFAT-dependent transcriptional activity may be useful in the assessment of T cell responses, T-cell-based adoptive therapies, vaccination strategies and immunosuppressive drugs.

Animals↗

[Monoclonal antibodies and uveal melanomas].

The authors, who have succeeded since 1976 in cultivating cells of ocular melanoma in continuous lines report the different stages for producing specific monoclonal antibodies. They particularly insist on the demonstration, through radioimmunoassay, of the specificity of marked monoclonal antibodies, on the immunohistochemical study and on biodistribution. From these data, an immunotherapy protocol has been perfected and starts being applied to human beings.

Animals↗