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Biomedical subjects

M Walsh

Publications and source records attributed to M Walsh.

At least 253 records · Page 14Linked to original sources

Metabolic response of Acylation Stimulating Protein to an oral fat load.

Acylation Stimulating Protein (ASP) is a small (mol wt 14,000), basic (pI 9.0) protein present in human plasma. When examined in vitro with normal human cultured skin fibroblasts and adipocytes, ASP appears to be the most potent stimulant of triglyceride synthesis yet described. In this study, a competitive ELISA assay for ASP has been developed using immunospecific polyclonal antibodies, and ASP levels have been measured in seven normal subjects. Following an oral fat load, a sustained significant increase in ASP occurs, whereas after an oral glucose load, ASP levels do not change significantly. These responses are entirely opposite to those of insulin, which rises sharply but transiently after an oral glucose load but is unchanged after an oral fat load. Both the fasting and peak ASP levels were significantly related to the postprandial lipemia. These data provide the first in vivo evidence that Acylation Stimulating Protein may play an important physiological role in the normal response to an oral fat load.

Adult↗

Increased circulating atrial natriuretic factor (ANF) release during induced ventricular tachycardia.

During sustained ventricular tachycardia (VT), there is usually a rise in mean atrial pressure. Atrial natriuretic factor (ANF) is a peptide released by the atria in response to increased atrial pressure or distension. ANF causes arterial vasodilation and natriuresis in man, and may contribute to the polyuria noted during tachycardia. We hypothesized that induction of sustained VT would cause elevation of right atrial pressure and lead to increased release of ANF. We measured mean arterial pressure, right atrial pressure, VT cycle length, atrial cycle length, plasma norepinephrine, and central ANF in 11 patients during 20 episodes of VT. The mean cycle length of induced tachycardia was 335 +/- 15 msec, with a mean atrial cycle length of 547 +/- 43 msec. Baseline plasma ANF was 70 +/- 11 femtomoles per milliliter and increased to 133 +/- 22 fmol/ml (p less than 0.001) after 4 minutes of VT. There was a decrease in mean arterial pressure from 87 +/- 3 to 66 +/- 3 mm Hg, and a rise in mean right atrial pressure from 4.0 +/- 0.8 to 11 +/- 1 mm Hg (p less than 0.001). The change in plasma ANF was quite variable among individual patients and was correlated with changes in mean right atrial pressure but poorly correlated with changes in mean arterial pressure, plasma norepinephrine, and atrial cycle length. Our data demonstrate that significant increased in ANF levels occur during sustained VT and are associated with increased right atrial pressure.

Atrial Function↗

Atrial natriuretic factor release is enhanced by incremental atrial pacing.

There is ample evidence from animal models indicating that secretion of atrial natriuretic factor (ANF) can be induced by an increase in atrial contraction frequency or atrial distension. The influence of these stimulatory signals on ANF secretion in humans has not been fully elucidated. We assessed the responses to graded right atrial pacing in 28 patients (aged 33 to 70 years) at rates of 100, 125, and 150 beats/min on right atrial pressure, left atrial size (by two-dimensional echocardiography in 9 of 28 patients), and circulating plasma ANF levels. At pacing rates of 125 and 150 beats/min, ANF levels increased from a baseline value of 64 +/- 9 fmol/ml (mean +/- SEM) to 89 +/- 13 fmol/ml (pp less than 0.05) and to 132 +/- 17 fmol/ml, respectively (p less than 0.001). Right atrial pressure increased from a baseline value of 4.1 +/- 0.7 mm Hg to 4.5 +/- 0.6 mm Hg at a pacing rate of 125 beats/min (p less than 0.05) and to 6.1 +/- 0.8 mm Hg at a pacing rate of 150 beats/min (p less than 0.001). Left atrial dimension increased from a baseline value of 44.5 +/- 3 mm to 49.5 +/- 3 mm at a pacing rate of 125 beats/min (p less than 0.05) and increased further to 52.5 +/- 3 mm at a pacing rate of 150 beats/min (p less than 0.001). No significant changes in atrial pressure or size or in plasma ANF were observed at a pacing rate of 100 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Dental disease, acute sinusitis and the orthopantomogram.

This study was undertaken to determine the incidence of undiagnosed apical disease in acute unilateral sinusitis and to evaluate the role of Orthopantomograms (OPGs). Our results, with an incidence of 10 per cent, are in agreement with the findings of Formby (1960) and we conclude that OPGs are not justified in the routine investigation of acute sinusitis.

Humans↗

The process of parenting a child with a disability: normalization through accommodations.

Professionals commonly advise parents of disabled children to raise their children as they would children who were not disabled. The purpose of this study was to describe the management styles used by the parents of 15 children and adolescents with osteogenesis imperfecta. In particular, the behavioural strategies related to providing a normalized existence for the child and the family are discussed. Sources of threats, validation, and support for the process are also described. The convenience sample of parents was selected from the appointment calendar of a specialty clinic in a midwestern philanthropic, paediatric-orthopaedic referral hospital. Qualitative interview data were gathered using a semi-structured guide. During interviews parents described behavioural strategies they used to normalize their child's and family life. Data were analysed using a previously developed framework of normalization. This work of normalization was described as a constant process of active accommodation to the changing physical and emotional needs of the child or adolescent. It was initiated out of practical necessity at birth as a conscious solution to problems with activities of daily living, relating to the child, and engaging in family activities. Certain events constituted 'threats' to normalization and served as an impetus for parents to alter behavioural strategies. Implications for clinical practice and research are explicated.

Activities of Daily Living↗

Effect of indomethacin in the late phase of coxsackievirus myocarditis in a murine model.

Previous studies have shown that indomethacin administered during the early phase of experimental myocarditis may exacerbate the disease process. It is unknown whether late administration of this agent is safe. Therefore, the effect of indomethacin administration during the late phase of coxsackievirus B3 murine myocarditis was investigated. Forty 3-week-old CD1 mice each received a 3 x 10(4) median tissue culture-infective dose of coxsackievirus intraperitoneally. On day 10 of infection, mice were randomized to receive either indomethacin or normal saline solution for 10 days, and 10 mice from each group were killed on days 20 and 30 of infection. Heart weight and size and serum atrial natriuretic peptide were similar in both groups on days 20 and 30. On day 20, pathologic scores for the degree of inflammation and necrosis were 1.7 and 1.0 for the indomethacin group versus 1.4 and 1.7 for the saline solution group. On day 30, pathologic scores were 0.3 and 0.6 for the indomethacin group versus 0.5 and 0.6 for the saline solution group. In addition, mineralization was absent in indomethacin-treated animals on day 20 after infection, but it was present in half of the control animals at that time. The degree of mineralization did not differ on day 30 between the two groups. These findings suggest that indomethacin given in the late phase of coxsackievirus myocarditis has no deleterious effects at 30 days.

Animals↗

Resection of parathyroid tumor in the aorticopulmonary window without prior neck exploration.

Of 522 patients with hyperparathyroidism operated on from 1973 to 1987 at our institution, there were seven (1.3%), each with an ectopic, hyperfunctioning mediastinal parathyroid adenoma, who required median sternotomy. In three of these seven patients, the tumor was located in the aorticopulmonary window. A 61-year-old woman with primary hyperparathyroidism had a preoperative thallium-technetium subtraction scan that showed thallium uptake at the base of the heart without any uptake in the neck. After further workup and without prior neck exploration, a parathyroid adenoma was found in the aorticopulmonary window through a median sternotomy. Six months later, serum calcium, phosphorus, and parathyroid hormone values remain normal. Two other cases of parathyroid adenoma in the aorticopulmonary window are presented. Of these two patients, the thallium scan was a key element in the immediate mediastinal exploration of one, who was transferred from another hospital comatose and intubated, in acute hypercalcemic crisis. Since mediastinal parathyroid tumors that necessitate median sternotomy occur in less than 2% of patients with primary hyperparathyroidism, we do not advocate routine preoperative localization studies before an initial cervical operation; localization, however, may be justified in selected cases, such as in critically ill patients or in instances of acute hyperparathyroidism, when the first operation needs to be curative.

Adenoma↗

The effect of a plasma protein fraction on lipid synthesis in cultured skin fibroblasts from normals and patients with hyperapobetalipoproteinemia.

Lipid synthesis was measured in cultured skin fibroblasts obtained from normals and patients with Hyperapobetalipoproteinemia (HyperapoB). Using lipoprotein-deficient serum medium, triglyceride synthesis and cholesterol esterification were greater in normals than in HyperapoB due to differences in de novo synthesis, not to differences in re-esterification or to different rates of hydrolysis. When normal and HyperapoB cells were incubated in serum-free medium, however, lipid synthesis was the same. Serum was then fractionated chromatographically and a partially purified protein fraction shown to be responsible for the stimulatory effect in normals.

Adult↗

Stimulation of fatty acid uptake and triglyceride synthesis in human cultured skin fibroblasts and adipocytes by a serum protein.

Lipoprotein deficient serum has been shown to enhance lipid synthesis in cultured normal human skin fibroblasts incubated in the presence of oleate-albumin. The factor responsible is nondialyzable and trypsin sensitive. The stimulation is proportional to the concentration of lipoprotein deficient serum in the media and is present at all oleate concentrations and incubation times assayed. The protein has been partially purified by column chromatography to yield a Peak II fraction which stimulates triglyceride synthesis in both fibroblasts and isolated human adipocytes. The stimulation is dependent on the concentration of protein fraction and increases to an apparent saturation level of 200% in fibroblasts. Triglyceride synthesis, however, increases to a much greater extent in adipocytes and did not demonstrate saturation at the maximum Peak II protein concentration assayed. These results suggest that human serum contains a protein which stimulates fatty acid uptake and esterification by adipose tissue.

Adipose Tissue↗

Tissue-specific gene expression results from a purine- and pyrimidine-free diet and 6-mercaptopurine in the rat small intestine and colon.

Dietary purines and pyrimidines are not considered to have a nutritional role, much less a direct effect on the functioning of the gastrointestinal tract. We found that a dramatic decrease in adult rat small intestinal and colonic total ribonucleic acid (RNA) results from the removal of dietary purines and pyrimidines or the administration of 6-mercaptopurine. Ribonucleic acid hybridization analysis indicated specific decrease of the messenger ribonucleic acid (mRNA) for the purine salvage enzymes hypoxanthine-guanine phosphoribosyl transferase and adenine phosphoribosyl transferase in the small intestine and proximal colon but not in the liver of animals fed a diet lacking purines and pyrimidines. Levels of intestinal and hepatic beta-actin mRNA transcripts were generally not depressed by either diet or by the administration of 6-mercaptopurine. Liver hypoxanthine-guanine phosphoribosyl transferase and adenine phosphoribosyl transferase mRNAs were unaffected by the change in diet but were lowered by the administration of 6-mercaptopurine. These data indicate that nutrition and 6-mercaptopurine affect both total RNA, and individual mRNA concentrations at specific sites in the gastrointestinal tract. These findings are of potentially great significance because the regulation of intestinal total RNA levels and purine salvage mRNAs by both 6-mercaptopurine and a purine- and pyrimidine-free diet suggests a potential mechanism by which dietary components differentially control specific proteins synthesized in the body. These findings may be related to the efficacy of 6-mercaptopurine as well as so-called elemental diets as therapeutic agents in chronic inflammatory bowel disease (i.e., Crohn's disease).

Adenine Phosphoribosyltransferase↗

Kyrle's disease.

Kyrle's disease is a chronic, genetically determined, hyperkeratotic disorder occurring in the middle forties. We report fourteen cases of this disorder in a population of 1.5 million over a period of 15 years. We observed a female/male ratio of 6:1. Straw-colored keratotic plugs and flat scale show a marked predisposition for the calf, the tibial region, and the posterior part of the thigh. They vary in size from 1 to 4 mm, and there is occasional plaque formation. No koebnerization or pruritus was noted, and no statistically significant association with hepatic, renal, or diabetic disorders could be demonstrated. Microscopic features showed a consistent pattern of keratotic plug formation, with the plug sitting in an invaginated atrophic epidermis, and underlying dermal histiocyte and lymphocyte aggregation. All lesions contained orthokeratosis and parakeratosis, with some sections showing abnormal keratinization. Sodium dodecylsulfate gel electrophoresis did not demonstrate the presence of abnormal keratin bands.

Adult↗