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Biomedical subjects

L Scott

Publications and source records attributed to L Scott.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of a light-regulated gene encoding a new phycoerythrin-associated linker protein from the cyanobacterium Fremyella diplosiphon.

Cyanobacteria utilize multimeric protein complexes, the phycobilisomes, as their major light-harvesting antennae. Associated with the chromophorylated phycobiliproteins in these complexes are nonpigmented proteins, designated linker proteins. These linker proteins are believed to mediate assembly of the phycobilisome and energy transfer to the photosynthetic reaction center. We cloned and sequenced a gene, cpeE, encoding a previously uncharacterized linker protein which is expressed in green light in Fremyella diplosiphon. This gene is part of an operon containing two other phycoerythrin-associated linker genes, cpeC and cpeD. Transcription of the cpeCDE operon in green light results in two predominant species of mRNA of approximately 2,100 and 3,200 nucleotides. The shorter transcript encodes only CpeC and CpeD, while the longer contains the coding regions for all three linker proteins. By altering the pH of the resolving gel and the running buffer during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, this third linker protein CpeE can be resolved from the rod-core linker and the other rod linker proteins. The three proteins have an overall similarity of approximately 62%, and the genes encoding the three proteins are approximately 59% identical.

Amino Acid Sequence↗
PubMed1990

Endothelial cell stimulation of smooth muscle glycosaminoglycan synthesis can be accounted for by transforming growth factor beta activity.

Endothelial cell conditioned medium (ECCM) contains a factor which markedly stimulates smooth muscle cell (SMC) glycosaminoglycan (GAG) synthesis. We report here that the factor responsible is transforming growth factor beta (TGF-beta) as assessed by (1) protease and thiol sensitivity, (2) heat and acid enhancement of ECCM activity, and (3) neutralisation of ECCM activity by anti-TGF-beta-immunoglobulin. Anti-TGF-beta-neutralisation was effective against increases in both sulphated and non-sulphated GAG. Previous studies showed that ECCM from EC of varying densities stimulated individual GAG to varying degrees. ECCM from low density EC preferentially stimulated hyaluronic acid (HA) whereas ECCM from intermediate and high density cultures stimulated increasing amounts of sulphated GAG. Exposure of SMC to varying concentrations of TGF-beta produced a similar pattern Exposure of SMC to varying concentrations of TGF-beta produced a similar pattern of response. Very low amounts of TGF-beta (less than 10-500 pg/10 cells) stimulated a marked and significant increase in HA synthesis. Increase in chondroitin sulphate 4/6 was most marked at TGF-beta levels from 500-1000 pg/10(6) cells. At levels above 1000 pg/10(6) cells both HA and sulphated GAG synthesis decreased but still remained elevated above controls. These findings indicate that TGF-beta alone can account for the changes in SMC GAG synthesis stimulated by ECCM. It was also found, however, that heat-treated SMC conditioned medium stimulated SMC GAG synthesis, thus SMC may contribute to the control of their own GAG synthesis through autocrine TGF-beta activity.

Animals↗
PubMed1990

Clinical evaluation of an acetaminophen meter for the rapid diagnosis of acetaminophen intoxication.

STUDY OBJECTIVES: To test the accuracy of a newly developed meter that determines serum acetaminophen concentration after a 30-second analysis of one drop of whole blood. DESIGN: Sixty-six blood samples from patients with known or suspected drug overdose were analyzed for the presence of acetaminophen. In all cases determination of serum acetaminophen concentration was performed simultaneously with the meter and by a reference laboratory. SETTING: Eligible patients were those who presented during a nine-month period to the emergency departments of two tertiary care hospitals (including a pediatric hospital). RESULTS: Thirty-one specimens had a laboratory-confirmed detectable acetaminophen concentration. The meter identified these toxic specimens in all cases; there were no false-negatives (sensitivity, 100%). Among the 35 specimens not containing acetaminophen, the meter invariably confirmed a nondetectable serum acetaminophen concentration (specificity, 100%). Acetaminophen measurements by the meter correlated strongly with laboratory determinations (r = .985, P less than .001). Repeated testing of one specimen documented the precision and reproducibility of the meter's analysis; mean coefficient of variation was .08 in measuring toxic acetaminophen concentrations. Drug coingestion had no significant effect on the accuracy of the meter. Instrument accuracy was maintained after more than 100 uses without recalibration. CONCLUSIONS: This meter identifies the possibility of rapid and accurate determinations of serum acetaminophen concentration. The instrument is ideally suited for patients with acetaminophen poisoning in whom expeditious and appropriate administration of antidotal therapy is desired.

Acetaminophen↗
PubMed1990

Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia.

A randomized, double-blind, placebo-controlled, parallel-group clinical trial was carried out to compare 24-week periods of treatment with 1 g acetyl-l-carnitine twice daily and placebo in the treatment of patients with dementia of the Alzheimer type. A total of 36 patients entered the trial, of whom 20 patients (7 active, 13 placebo) completed the full 24 weeks. Whilst several of the efficacy indices showed little change in either group during the trial, there was an apparent trend for more improvement in the acetyl-l-carnitine group in relation to the Names Learning Test and a computerized Digit Recall Test, both related to aspects of short-term memory. Similarly, there was a trend for reaction time in the computerized classification test to show less deterioration in the active treatment group. Changes within groups, and changes between groups, failed to reach statistical significance, at least partially because of the small number of patients available for analysis. Two indices of overall therapeutic benefit showed a trend for less deterioration in the active-treatment group than in the placebo group. Nausea and/or vomiting occurred in 5 patients in the acetyl-l-carnitine group. Laboratory tests revealed no signs of drug toxicity. The results suggest that acetyl-l-carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia, particularly those related to short-term memory.

Acetylcarnitine↗
PubMed1989

Scheduling lectures in a teaching hospital.

A modelling technique has been devised that can be used to assist in scheduling lectures for medical students in teaching hospitals. The model takes into account the various clinical commitments that are faced by students and the fact that some of these commitments have a fixed timetable while others are relatively flexible. A simple model is framed for the conflict caused by a particular lecture period in terms of the number of commitments which clash. A computer program has been written that produces graphical output illustrating the effects of various scheduling options. The output from the computer program can be used by decision-makers to examine different options for scheduling lectures and also to explore the effects of rescheduling other clinical activities where there is flexibility so to do.

Computer Simulation↗
PubMed1989

Inhibition of ovarian cancer cell proliferation in vivo and incorporation of 3H-thymidine in vitro after follicle regulatory protein administration.

Follicle regulatory protein immunoreactivity and biologic activity were measured in ascites from a patient with juvenile granulosa cell tumor. Microscopic examination of immunohistochemical staining of a juvenile granulosa cell tumor with anti-follicle regulatory protein antisera showed homogeneous cytosolic expression of follicle regulatory protein throughout the tumor. Tumor cells were injected subcutaneously into nude mice. Partially purified follicle regulatory protein (50 micrograms/day) was then injected daily for 10 days, or for 25 days once the tumor became palpable. Treatment with follicle regulatory protein significantly slowed the rate of tumor growth with both treatments. To test the tissue specificity of the effect, a metastatic, well-differentiated endometrial adenocarcinoma was also grown in nude mice. Follicle regulatory protein treatment did not alter the rate of tumor growth. An in vitro clonigenic assay confirmed these in vivo results. Partially purified follicle regulatory protein had a biphasic effect on the proliferation of juvenile granulosa tumor cell but did not affect the proliferation of endometrial adenocarcinoma cells. Clonigenic assays were performed on five ovarian adenocarcinomas passaged in vitro, and these tumor cells exhibited a biphasic response to follicle regulatory protein. Immunoneutralization studies showed that this biphasic response was due to impurities in the follicle regulatory protein preparations. The longer the exposure of the tumor cells to follicle regulatory protein, the greater the degree of inhibition of proliferation. In summary, administration of follicle regulatory protein slowed tumor growth through a direct effect on the tumor cell rather than an indirect effect on the hormonal or immune status of the host.

Adenocarcinoma↗
PubMed1988

Effects of tolmetin sodium dihydrate on normal and postsurgical peritoneal cell function.

Recent studies utilizing intraperitoneal (i.p.) administration of NSAIDs to rabbits after surgical injury to the parietal peritoneum demonstrated macrophage involvement. NSAIDs are known to inhibit the metabolism of arachidonic acid to prostaglandins, which in turn modulate a variety of macrophage functions. Studies presented here examine the effects of tolmetin administration on peritoneal resident and post-surgical leukocyte functions, such as phagocytosis, the release of superoxide anion and tumoricidal activity. Rats, either non-surgical or following peritoneal surgery, were injected i.p. with tolmetin. At various times after treatment, the rats were sacrificed and peritoneal cells collected by lavage. The phagocytic capability of peritoneal leukocytes was transiently decreased 5-7 days after the administration of tolmetin to normal animals. However, administration of tolmetin during surgery extended the length of time that phagocytic capability was enhanced. In non-surgical controls, there was an elevation in superoxide anion release and tumoricidal activity 24 h after tolmetin administration. Superoxide anion release was suppressed at days 5 and 7 after treatment, but returned to control levels by day 14. Intraoperative administration of tolmetin significantly elevated superoxide anion release at days 3 and 5, phagocytosis at days 7 and 14 and tumoricidal activity at day 3. These studies suggest that compounds which suppress prostaglandin synthesis can modulate the function of resident and post-surgical peritoneal cells.

Animals↗
PubMed1988

Inflammatory pseudotumors in children.

Inflammatory pseudotumors are so named because they mimic malignant tumors clinically and radiologically. Most often seen in the lungs of young adults, they consist of localized proliferations of mononuclear inflammatory cells and myofibroblasts. There are scattered reports of these tumors occurring in various sites in children. We report five cases of these rare lesions in children; four arising intraabdominally and one in the lung. In contrast to the usual presentation in adulthood, these children were all previously healthy. One child, with the tumor arising from the urinary bladder, was originally diagnosed as having a malignant sarcoma and underwent pelvic exenteration and chemotherapy for this subsequently-proven benign lesion. Local recurrence occurred in one case. Total excision is indicated and is usually possible without unacceptable morbidity. Our cases and a review of the literature point out the importance of pathologic differentiation of these lesions from malignancy with early appropriate surgery.

Child↗
PubMed1987

A comparative study of the rate-limiting enzymes of cholesterol synthesis, esterification and catabolism in the alloxan-induced diabetic rat and rabbit.

1. Hyperlipidaemia is associated with diabetes mellitus. 2. A comparison of cholesterol synthesis and utilization in alloxan-induced diabetic rats and rabbits revealed that interspecies differences existed only in the response of the key enzymes regulating cholesterol utilization, namely cholesterol 7 alpha-hydroxylase and ACAT in the liver and intestine respectively. 3. The activity of cholesterol 7 alpha-hydroxylase was enhanced in diabetic rats but was markedly reduced in diabetic rabbits. 4. Intestinal ACAT activity, though unchanged in diabetic rats was reduced in diabetic rabbits. 5. Such species differences in cholesterol utilization may underlie the different degree of susceptibility to hypercholesterolaemia that exists between these two species.

Animals↗
PubMed1987

A comparative study of the rate-limiting enzymes of cholesterol synthesis, esterification and catabolism in the rat and rabbit.

1. The rat and rabbit are amongst the animal models most widely used in the study of human atherosclerosis, a disease state correlating with disturbances in cholesterol metabolism. 2. In order to relate the key regulatory enzymes of cholesterol synthesis, esterification and catabolism in the rat and rabbit to their differing degree of susceptibility to atherosclerosis, enzyme levels and their properties were determined in liver and intestine of both species. 3. Hepatic HMG CoA reductase and cholesterol 7 alpha-hydroxylase levels were significantly higher in the rat than in the rabbit, while intestinal HMG CoA reductase activity in the two species was comparable. Conversely, the capacity to esterify cholesterol as measured by ACAT activities was considerably greater in both sites in the rabbit compared to the rat. 4. The data suggest that differences in the key regulatory enzymes of cholesterol metabolism in both liver and intestine may reflect different methods of cholesterol utilization in the two species.

Animals↗
PubMed1987

Changes in collagen fibril diameters across artery walls including a correlation with glycosaminoglycan content.

Collagen fibril diameters were measured at regular intervals across the walls of numerous arteries from human, pig and rat. In all vessels the smallest fibrils (mean-fibril diameters of 30-40 nm) occurred in the intima and inner media and the largest fibrils (MFDs 50-100 nm) in the outer adventitia. Between these two regions fibrils progressively increased in size. Circumferential and axial fibrils were of similar size and showed similar patterns of increase. At each sample site there was a range of diameters and frequency distributions were often multimodal with peaks 8 nm, or multiples of 8 nm, apart. Amounts of total and individual glycosaminoglycans (GAG) were determined at regular intervals across the wall of pig aorta and total and sulphated GAG levels were also determined at intervals across rat carotid artery using autoradiographic detection of incorporated [3H] glucosamine and 35S. In both vessels there was a strong correlation between decreasing GAG and increasing MFDs and over a narrow MFD range of 40 to 60 nm. These results demonstrate that collagen fibril diameters are excellent indicators to GAG levels and may be useful for making predictions about GAG levels in areas too small to sample biochemically.

Adult↗