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Biomedical subjects

S Kennedy

Publications and source records attributed to S Kennedy.

At least 289 records · Page 16Linked to original sources

Selective morphologic alterations of the cardiac conduction system in calves deficient in vitamin E and selenium.

Vitamin E and selenium (E-Se) deficiency causes necrosis of the contractile myocardium in many species but does not usually affect the cells of the conduction system. In the present study, experimental E-Se deficiency in cattle produced preferential degeneration and necrosis of Purkinje cardiocytes. Calves fed deficient diets for 127-137 days had sublethal damage characterized histologically by sarcoplasmic accumulation of lipopigment granules; ultrastructurally, these granules corresponded to cytolysosomes that had a heterogeneous ultrastructure. Alterations in necrotic cells included mitochondrial mineralization, sarcoplasmic condensation, and plasmalemmal fragmentation. Necrosis of Purkinje cells was followed by macrophagic penetration of the external lamina, phagocytosis of necrotic sarcoplasm, and repair by fibrosis. Furthermore, E-Se depletion of calves resulted in only minimal alterations in the contractile myocardium. In contrast, feeding supplements of polyunsaturated fatty acids to E-Se-deficient calves intensified the Purkinje cell damage but also resulted in widespread degeneration and necrosis of the contractile myocardium. Accumulation of lipopigment supports a pathogenetic role for lipoperoxidation in development of the cardiac lesions of E-Se deficiency. These lesions constitute a unique example of preferential damage to Purkinje cardiocytes. This model offers an attractive method of studying damage and repair to the cardiac conduction system.

Animals↗

Antiproliferative effects of suramin on lymphoid cells.

Suramin, a polyanionic drug used in the treatment of Rhodesian and Gambian trypanosomiasis and more recently in the acquired immune deficiency syndrome, is a potent inhibitor of the constitutive mammalian DNA polymerases alpha, beta, and gamma and the lymphoid-specific polymerase terminal deoxynucleotidyl transferase. To define the effect of this inhibition on cell proliferation, we studied the effect of suramin on several cell lines in culture and in mice in vivo. Suramin, at 200 micrograms/ml (which is regularly achieved in the plasma of patients), had no effect on the proliferation of 4 of 5 nonlymphoid cell lines. In contrast, exposure of 10 lymphoid cell lines to 200 micrograms/ml suramin for 4 days caused significant growth inhibition in 8 of these 10 lines. Suramin given i.p. to BALB/cBYJ mice at clinically relevant doses (15-60 mg/kg) caused profound and prolonged thymic atrophy within 5-7 days of drug administration (greater than a 90% weight loss in mice treated with 60 mg/kg). Thymic sections revealed severe cortical loss, prominence of dendritic cells, and vacuolated macrophages. Liver, peripheral blood, spleen, kidney, and total body weights were not affected. The apparent selective lymphocytotoxicity of suramin may represent an important property of this drug. We speculate that this may account for the persistent immune suppression reported in suramin-treated acquired immune deficiency syndrome patients.

Animals↗

Bovine, porcine and ovine picornaviruses: identification of viruses with properties similar to human coxsackieviruses.

Eleven bovine, 19 porcine, and 3 ovine picornaviruses were tested for their ability to grow in the presence of the viral inhibitors 2-(alpha-hydroxy-benzyl)- benzimidazole (HBB) and guanidine-HC1 (GHC1). The nature of the lesions produced by inoculation of newborn mice with these viruses was also investigated. Nine bovine viruses were inhibited by both compounds, and produced skeletal myonecrosis in mice, suggesting similarities to the human coxsackie group B viruses and indicating potential pathogenicity for bovine species. One bovine virus (VH7) was inhibited by GHC1 but not by HBB and caused widespread skeletal muscle damage in mice typical of coxsackie group A viruses. Another bovine virus (F266a) was inhibited only by HBB. None of the porcine or ovine viruses showed significant inhibition by either compound nor produced lesions in mice.

Animals↗

Vesicular stomatitis virus P function depends on cellular growth cycle.

The P function of vesicular stomatitis virus (VSV) is defined as the viral function which results in a reduced rate of total protein synthesis (viral plus cellular) arising from a nonspecific reduction in the efficiency of the translational machinery in infected cells. The existence of P function has been challenged by Lodish and Porter who were unable to detect it in L-strain mouse cells infected with wild-type VSV (HR) or, as expected, with the P- mutant, T1026-R1. Although other groups have subsequently confirmed the existence of P function and the difference between HR and T1026-R1, we have sought an explanation for the difference between Lodish and Porter's results and those of other laboratories. We show that the VSV P function depends on the phase of the growth cycle of infected L-cell cultures. In very early exponential phase, as used by Lodish and Porter, HR has very little demonstrable P function; as the growth cycle proceeds toward stationary phase, P function becomes more and more manifest. Under the same conditions, T1026-R1 shows no P function throughout the growth cycle. Furthermore we show that the VSV M protein mutant tsG31 has a P++ phenotype reducing total protein synthesis below that seen with wild-type HR. P function can be observed in cells infected with tsG31, even early in the exponential phase of the cellular growth cycle.

Animals↗

Renal lesions in cattle fed sodium hydroxide-treated barley.

Ten 14-week-old calves were fed a diet containing 87.5% NaOH-treated barley, and killed after 29, 65, 75, 117, 140, 179, 314, 338, and 408 days. Eight control calves were fed a diet in which untreated rolled barley was substituted for alkali-treated grain. Calves receiving NaOH-treated barley became polyuric with urine pH ranging from 9.0 to 9.5, and had significantly raised plasma creatinine levels on day 29. Other clinical findings were normal, and there were no other significant alterations in blood. At necropsy, bilateral renal lesions consisted of white cortical foci, medullary stippling, and the presence of uroliths in the renal papillae and calyces. Microscopic changes included tubular dilatation, atrophy, necrosis, and mineralization, interstitial fibrosis with mononuclear cell invasion and consequent glomerular changes. It appeared that glomerular and interstitial changes were secondary to primary tubular damage. No abnormalities were detected in control calves. Feeding of NaOH-treated barley can result in nephrotoxicosis in cattle.

Animal Feed↗

Pathology of experimental ureaplasma mastitis in ewes.

One mammary gland of each of nine primum partum suckling ewes was inoculated with ureaplasma 8 weeks post-partum. Infected glands were swollen, hot, and painful from 16 hours post-infection. Subsequently there was agalactia and reduction in gland size. Histopathologic and ultrastructural examination indicated that the acute phase of the induced mastitis was characterized by necrosis of secretory epithelium with a neutrophil, eosinophil, and macrophage response. Subsequently there was lymphoid infiltration, acinar involution, and fibrosis. This report confirms the pathogenicity of ureaplasma for the ovine mammary gland, and is the first description of the pathologic features of ureaplasmal mastitis in sheep.

Animals↗

Risk factor modification in hypertension--success and failure.

A group of 175 patients have attended for four years a microcomputer based, nurse practitioner managed clinic for the long term care of hypertension. Improvement in blood pressure (BP) control was seen initially and has been maintained. Drug treatment has been with a beta blocker followed if necessary by a diuretic and/or a vasodilator. Despite individual dietary and 'stop smoking' advice, there was no marked change in body weight while only males reduced smoking. A significant increase in non fasting serum cholesterol (6.4 +/- 1.3 to 6.6 +/- 1.3 mmol/l) and glucose (5.5 +/- to 6.1 +/- 2.5 mmol/l) was seen overall, but was restricted to those patients taking a thiazide diuretic (with or without other drugs). These findings indicate the need for a more systematic collection of information on effects of long term treatment and for the development of better strategies for improving lifestyle.

Adrenergic beta-Antagonists↗

Psychology and health: contributions of psychology to the improvement of health and health care.

Psychology as both a science and a profession has been closely identified with other disciplines in the broad field of health since the turn of the present century. Recent advances in health care have reinforced the growing belief that the promotion of health and the prevention and treatment of illness can be greatly enhanced by incorporating the scientific findings and modern techniques of psychology into everyday practices. This review outlines the contributions of psychology to health care throughout the world; only some of the most timely and relevant issues are mentioned, together with examples of current work in the field. After an introductory overview, special attention is given to each of the major areas within the broad field of health care where psychological applications have been particularly useful.

Community Mental Health Services↗

Experimental myopathy in vitamin E- and selenium-depleted calves with and without added dietary polyunsaturated fatty acids as a model for nutritional degenerative myopathy in ruminant cattle.

Fourteen calves, 14 weeks old, fed a low vitamin E and selenium diet based on sodium hydroxide-treated, selenium-deficient barley showed a rapid decline in plasma alpha-tocopherol, a gradual decline in erythrocyte glutathione peroxidase (GSHPX) activity, elevated plasma creatine kinase (CK) activity, teeth grinding and (in three cases) electrocardiographic changes, but no clinical abnormalities after 127 to 137 days. Necropsy of six depleted calves at that stage revealed pale muscles in two animals and mild histopathological lesions of skeletal myopathy in all six calves. Ten control calves were fed a similar diet supplemented with alpha-tocopherol and selenium. Plasma alpha-tocopherol and erythrocyte GSHPX activity remained high in these calves and no clinical abnormalities or evidence of myodegeneration were observed. When protected linseed oil was fed as a source of polyunsaturated fatty acids to the remaining eight depleted calves, rapid elevations in plasma CK activity and linolenic acid associated with a variety of cardiopulmonary and locomotory signs, electrocardiographic changes and myoglobinuria occurred within six to 11 days. Necropsy revealed widespread severe skeletal myodegeneration (eight calves) and myocardial lesions (five calves) with preferential involvement of the left ventricular myocardium. Clinical signs and pathological changes were similar to those reported in field outbreaks of nutritional degenerative myopathy in ruminant cattle and establish the experimental regime as the first successful model for reproduction of this disease.

Animals↗

A successful psychiatric training program for medical residents.

The psychosocial skills of 24 PGY I medical residents receiving psychiatric training every other week during the internship year were evaluated and compared to a control group of 13 PGY I residents. After the internship year, the psychiatrically trained residents showed an increase in their ability to recognize emotional problems, whereas the control group recognized less depression. Psychiatrically trained residents were more sophisticated in psychosocial problem descriptions and plan formulations, whereas the control group formulated more poor psychosocial plans.

Clinical Competence↗

Inactivation of the alpha-haemolysin gene of Staphylococcus aureus 8325-4 by site-directed mutagenesis and studies on the expression of its haemolysins.

S. aureus strain 8325-4 was shown to produce alpha-, beta-, delta- and gamma-haemolysins by haemolytic assays and immunoblotting. Hybridization experiments indicated that a single copy of the alpha-haemolysin gene (hla) resides in the chromosome. Site-directed mutagenesis was used to inactivate the hla gene. This gene, which had previously been cloned in E. coli, was inactivated in vitro by inserting a fragment carrying an erythromycin resistance marker. Shuttle plasmids were constructed and transformed into 8325-4 and non-haemolytic recombinants enriched by a plasmid incompatibility technique. A previously isolated Tn551 insertion defective in alpha-haemolysin was not located in hla. It had pleiotropic defects in expression of alpha-, beta- and delta-haemolysins. Expression of alpha-haemolysin from a plasmid-located hla gene was very low. In contrast, hla-erm mutants were deficient only in alpha-haemolysin and allowed high level expression of the plasmid-borne hla gene. The Tn551 insertion is probably located in a gene encoding a positive regulatory element required for expression of several exoproteins. An hla-erm mutant was less virulent than the otherwise isogenic 8325-4 hla+ strain in a mouse peritonitis model, confirming that alpha-haemolysin is an important virulence factor.

Bacterial Toxins↗

Neuropathology of experimental 3-nitro-4-hydroxyphenylarsonic acid toxicosis in pigs.

Twenty pigs were fed a diet containing 187.5 mg kg-1 of 3-nitro-4-hydroxyphenylarsonic acid (3-nitro). Ten pigs were euthanized at intervals up to 29 days, 3-nitro was withdrawn from the diet of the remaining pigs on day 30, and these animals were subsequently euthanized at intervals up to 49 days after commencement of the experiment. A nervous syndrome characterized by clonic convulsive episodes inducible by exercise, developed at day 11. Paraparesis was apparent at day 22 progressing to paraplegia by day 33 (3 days after cessation of 3-nitro feeding). Histopathologic examination revealed myelin and axonal degeneration in the white matter of the spinal cord coincident with the onset of nervous signs. Marchi-positive degeneration was present in the dorsal funiculus at cervical level at day 22. Lesions intensified with increasing duration of toxicosis and while degenerate fibers were seen in all funiculi, there was preferential involvement of the fasciculi gracilis and cuneatus, the peripheral regions of the ventral and lateral funiculi, and a discrete area of the dorsal region of the lateral funiculus. Peripheral and optic neuropathies were evident from day 32 but were always mild and focal. The experiment establishes 3-nitro as a central-peripheral neurotoxicant of pigs.

Animals↗

Psychiatric sequelae of subarachnoid haemorrhage.

Twenty cases with psychiatric disorder occurring after subarachnoid haemorrhage were studied. Seventy per cent had a research diagnostic criteria diagnosis of major depressive disorder, most of whom also had signs of persisting organic brain damage. Ten per cent of the cases committed suicide, and only 10% had made a full recovery from the psychiatric disorder. There was no significant association between the laterality of damage and the subsequent development of major depressive disorder, however, middle cerebral artery haemorrhage was over-represented in the sample.

Adult↗