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Biomedical subjects

S Farrell

Publications and source records attributed to S Farrell.

45 records · Page 3Linked to original sources

Entry of acetyl-L-carnitine into biosynthetic pathways.

[1-14C]Acetyl-L-carnitine was injected into fed and fasted mice and the time-course of distribution of 14C in various tissues and tissue components was determined. The major product was 14CO2. However, considerable quantities of radioactivity were localized in liver with much smaller quantities in heart, brain, skeletal muscle and kidney. Most of the 14C in liver was located in the fatty acids of phospholipids and triacylglycerols within 10 min after injection. The data demonstrate that the acetyl moiety of acetylcarnitine rapidly enters lipid biosynthetic pools in liver.

Acetates↗

Incorporation of platelet and leukocyte lipoxygenase metabolites by cultured vascular cells.

When arachidonic acid metabolism is studied during platelet-endothelial interactions in vitro, the predominant cyclooxygenase end products of each cell type (thromboxane B2 and 6-keto-prostaglandin-F1 alpha, respectively) are essentially completely recovered in the cell-free supernatants of these reactions. In contrast, 50% of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), the major lipoxygenase metabolite from platelets, is released into the cell-free supernatant. In investigating the basis of this observation, we have found that platelet lipoxygenase metabolites were generated to the same extent during these coincubations but became rapidly incorporated into the endothelial cells. The endothelial cell-associated 12-HETE was present not only as free fatty acid, but was also incorporated into cellular phospholipids and triglycerides. When purified 3H-12-HETE, 3H-5-HETE (the major hydroxy acid lipoxygenase product of leukocytes), and 3H-arachidonic acid (the common precursor of these metabolites) were individually incubated with suspensions of cultured bovine aortic endothelial cells or smooth muscle cells, different patterns of intracellular lipid distribution were found. In endothelial cells, 12-HETE was incorporated equally into phospholipids and triglycerides, whereas 5-HETE was incorporated preferentially into triglycerides, and arachidonic acid was incorporated into phospholipids. In smooth muscle cells, both 12-HETE and 5-HETE showed more extensive incorporation into triglycerides. The rapid and characteristic incorporation and esterification of platelet and leukocyte monohydroxy fatty acid lipoxygenase products by endothelial and smooth muscle cells suggests a possible physiologic role for these processes in regulating vascular function.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

HLA-DR expression in a human colonic carcinoma cell line.

A human colonic carcinoma cell line (HCA-7) isolated from a well differentiated mucoid adenocarcinoma of the colon has been maintained in vitro for 3 years. It spontaneously synthesizes HLA-DR which is mainly intracytoplasmic. Stimulation with lymphocyte conditioned medium and recombinant gamma-interferon results in enhanced synthesis of HLA-DR and the appearance of the antigen on the cell surface. A dose response study showed that maximal stimulation of the culture was achieved with 50 units/ml of recombinant gamma-interferon. Staining for HLA-DR was uneven being confined to focal areas of the monolayer, which is similar to the focal expression of HLA-DR seen in sections of adenocarcinoma of the colon. The functional significance of this phenomenon is unclear, but it may explain the presence of lymphoid infiltrates in tumours.

Adenocarcinoma↗

Computerization of undergraduate medical curriculum content.

A method is reported for the computerized storage and retrieval of informative summaries of the didactic portion of the first 3 years of the medical undergraduate curriculum utilizing the MICOM word processor and SORT 200 program with disc storage. Each lecture, small group session, laboratory or clinical experience summary is assigned a page of computer memory and is coded in the header line for various indices describing the session format, location, audiovisual usage, teacher and other demographics. The second line contains the lecture title and its situation within the teaching block. A summary of the teaching session follows. This was compiled and distilled from summaries prepared by the individual teachers, lecture handouts and the personal notes of the two medical students who divided the lectures equally between themselves and prepared individual summaries which were then exchanged. The resulting composite summary was returned to the teacher for comment and/or modification before entry onto the MICOM word processor. The SORT 2000 program permits search, selection and retrieval of the content of each teaching session from the data contained in the header line or any word, word segment or phase occurring in the summary. Reproduction of the data discs facilitates multiple access and allows each department or teaching block to review the complete curriculum quickly, identify redundancies and more fully integrate new or existing material.

Computers↗

Increases in HDL-cholesterol and the HDL/LDL cholesterol ratio during prolonged endurance exercise.

The influence of prolonged, low-intensity exercise (45% VO2max) until exhaustion on plasma lipid levels, in particular high-density lipoprotein cholesterol (HDL-C), and the time sequence associated with changes in these blood constituents was investigated in 10 trained subjects. The exercise consisted of walking on a motor-driven treadmill until exhaustion. Blood samples were drawn before, at 30 and 60 minutes after the beginning of exercise, at each hour thereafter until exhaustion, immediately before exhaustion, and after a 30-minute recovery period. At exhaustion the total cholesterol concentration was significantly elevated by 3% and rose another 3% during the recovery period. The HDL-C level was significantly elevated within two hours after the start of exercise and by exhaustion (about 4.5 hours of exercise) had risen to 52.5 +/- 2.3 mg X dL-1, which represented a 10.8% increase above the pre-exercise concentration (47.4 +/- 1.8 mg X dL-1). The HDL/LDL cholesterol ratio followed a pattern similar to that described for HDL-C. Plasma free fatty acids (FFA) also increased linearly during the exercise period but were not significantly correlated with HDL-C during exercise (r = 0.14). These results suggest that prolonged, low-intensity exercise can acutely improve the lipid profile of humans.

Adult↗

Endurance improved by ingestion of a glucose polymer supplement.

The effect of glucose polymer (GP) ingestion upon endurance performance during walking exercise at 45% VO2max was examined. Also, performance on a battery of psychomotor tests was assessed to determine if exhaustion from endurance exercise was related to central nervous system dysfunction. Ten trained male subjects ingested approximately 120 g of GP in four equally-divided dosages 60, 90, 120, and 150 min following the start of exercise. This treatment significantly increased time to exhaustion by 11.5% as compared to the control (C) group (GP=299.0 +/- 9.8 min; C=268.3 +/- 11.8 min). No difference in VO2 (1 X min-1) or perceived exertion was noted between treatments. As a result of the GP feedings the rate of carbohydrate utilization during the GP trial was 0.53 g X min-1 greater than during the C trial. However, during the GP trial plasma glucose did not fall below the pre-exercise level and was significantly higher than the C plasma glucose concentration at exhaustion. No differences in psychomotor performance between treatments or between rested and exhausted states for either the C or GP treatments were noted. These data suggest that exhaustion was not a result of hypoglycemia or central nervous system dysfunction and that glucose polymer supplements may enhance endurance capacity.

Blood Glucose↗

Possible functions of short-chain and medium-chain carnitine acyltransferases.

Several mammalian tissue contain water-soluble, branched chain acylcarnitines and other short-chain aliphatic acylcarnitines and also contain a broad spectrum of short-chain and medium-chain carnitine acyltransferase (CAT) activities. Although carnitine can stimulate the oxidation of branched chain alpha-ketoacids, it has not been established that carnitine is required for the oxidation of the alpha-ketoacids in the matrix of mitochondria. Rather it probably acts as a reversible sink for acyl residues, thereby generating CoASH, which can be used to maintain normal metabolism; thus carnitine would have a facilitative rather than an obligatory role. Microsomes and peroxisomes contain medium- and short-chain CATs. This occurrence is short- and medium-chain CATs in peroxisomes is consistent with carnitine's being involved in shuttling the chain-shortened products of beta-oxidation out of peroxisomes. Human urine contains a spectrum of short-chain acylcarnitines and data are presented that show a large amount of propionylcarnitine in the urine of the individual with a metabolic problem. The cumulative data are consistent with the conclusion that carnitine has multiple roles in mammalian metabolism, including the shuttling of beta-oxidation chain-shortened products out of peroxisomes in liver, the modulation of the acyl-CoA/CoASH ratio in mammalian cells, and the translocation of acetyl units for selective synthesis in a yeast.

Acetyl Coenzyme A↗

Detection of submicroscopic aberrations in patients with unexplained mental retardation by fluorescence in situ hybridization using multiple subtelomeric probes.

PURPOSE: To further assess the frequency of subtelomeric aberrations in a selected population and to examine the feasibility of a clinical testing. METHODS: Patients were selected based on the following criteria: (1) mental retardation (IQ < 70) or developmental delay with dysmorphic features; (2) a normal karyotype at the level of resolution of 450 to 500 bands; and (3) exclusion of other possible etiologies by a full genetic assessment and relevant tests. Fluorescence in situ hybridization (FISH) was performed using multiple subtelomeric probes. Abnormal findings were confirmed by 24-color spectral karyotyping or FISH with a specific subtelomeric probe, and family studies were carried out to determine inheritance. RESULTS: Clinically significant aberrations were detected in 6 of 150 proband patients (4%), while deletion of the 2q subtelomeric region appeared to be a common variant (6%). CONCLUSIONS: FISH with multiple subtelomeric probes is a valuable clinical test for establishing a definitive diagnosis for patients with unexplained mental retardation/developmental disorders.

Adult↗