Biomedical subjects

S Kennedy

Publications and source records attributed to S Kennedy.

At least 199 records · Page 11Linked to original sources

PubMed1995

Effect of N2O treatment/vitamin B12 deficiency in pigs on tissue concentrations of odd-numbered, branched-chain fatty acids.

Activity of the vitamin B12-dependent enzyme, methylmalonyl CoA mutase, was measured in the tissues of pigs, fed a diet which was low in cobalt and vitamin B12, and which were intermittently exposed to nitrous oxide until they displayed marked ataxia. Methylmalonyl CoA mutase activity was reduced in liver, kidney and brain. However, the methylmalonic acid concentration was reduced in liver and heart, in marked contrast to the expected increase which was only observed in brain. Liver and kidney also showed an unexpected reduction in the concentration of C17 odd-numbered fatty acids, possibly as a consequence of reduced propionate availability. Brain however, which had elevated methylmalonic acid concentrations showed no change in either odd-numbered or branched-chain fatty acids. These results suggest that nitrous oxide-induced neuropathy does not occur as a result of misincorporation of odd-numbered/branched-chain fatty acids in brain.

Animals↗

PubMed1995

Feeding corn oil to vitamin E-deficient pigs increases lipid peroxidation and decreases tissue glutathione concentrations.

Dietetic microangiopathy ("mulberry heart disease") is a common disease of weaned pigs in several countries. It is characterised by sudden death and has been associated with vitamin E deficiency. We investigated whether it could be induced by depleting pigs of vitamin E with or without a mild peroxidative challenge. In a 2 x 2 experiment, the effect on pigs of depletion of alpha-tocopherol and supplementation with alpha-tocopherol-stripped corn oil were investigated. Although dietetic microangiopathy was not induced, there was evidence of lipid peroxidation, as judged by increased concentrations of Fe++(-)induced 4-hydroxynonenal (4-HNE) and decreased amounts of linolenic acid (C18:3, omega-3) in tissue. Reduced glutathione (GSH) can conjugate to 4-HNE in an attempt to detoxify this highly toxic compound. GSH concentrations were decreased in skeletal muscle, but not in heart, of pigs that were depleted of alpha-tocopherol with or without supplementation with corn oil. The activity of glucose-6-phosphate dehydrogenase (G6PDH) was higher in heart than in skeletal muscles. It is postulated that sufficient NADPH may be produced in heart to maintain GSH concentrations at a level sufficient to conjugate the excess 4-HNE produced by alpha-tocopherol deficiency and/or oil supplementation.

Aldehydes↗

PubMed1994

Mass mortality of common dolphins (Delphinus delphis) in south west England due to incidental capture in fishing gear.

In the first quarter of 1992, 118 dolphin carcases, of which 54 were positively identified as common dolphins (Delphinus delphis), were found stranded on the coast of Cornwall and Devon. To determine the cause, detailed post mortem examinations were carried out on 38 of the carcases, and the results were compared with those from 20 common dolphins that stranded on the coast of Cornwall and Devon in the previous 15 months. There was no evidence that the deaths were due to an infectious or parasitic disease, or acute intoxication by any of the algal toxins, trace metals or chlorinated hydrocarbons measured. However, 30 of the 38 dolphins showed signs associated with incidental capture in fishing gear. Skin lesions characteristic of capture in a small-meshed net and the predominance of recently ingested Atlantic mackerel (Scomber scombrus) and pilchard (Sardina pilchardus) in the stomachs of the dolphins suggested that they had been caught in the trawl or purse seine nets used for these fish. There is insufficient information to explain why this high mortality occurred in 1992 and not in other years.

Animal Diseases↗

PubMed1994

Stress-induced modulation of the immune response in the developing rat pup.

Although substantial evidence has linked stressful events to immune changes in adult animals, little is known regarding the impact of stress on immune function during ontogeny. In the present study, 8-, 16-, and 20-day old rat pups were isolated from their mothers and littermates for 24 h; splenocyte responses to the mitogen Con A were assessed 72 h following reunion. A suppression of the mitogen response was obtained for 16- and 20-day old pups, but no effect was found in the 8-day-old animals, possibly due to the small sample size. These data offer a viable model from which to study further changes in immune responsiveness during ontogeny.

Aging↗

PubMed1994

Effects of dietary vitamin E and selenium on in vitro cellular immune responses in cattle.

Four groups of calves depleted of alpha-tocopherol and selenium (Se) were supplemented with alpha-tocopherol or Se or alpha-tocopherol and Se or received no supplement. In vitro lymphocyte proliferative responses were measured in fetal calf serum (FCS), in autologous serum and in pooled sera from each group. In FCS, the responses to pokeweed mitogen were significantly enhanced for calves supplemented with alpha-tocopherol. In autologous serum, the mean responses to keyhole limpet haemocyanin (KLH) were greatest for calves supplemented with Se alone. In pooled sera from each group, lymphocytes from calves supplemented with Se alone showed enhanced responses to KLH in the presence of serum from calves supplemented with alpha-tocopherol. The calves depleted of alpha-tocopherol had increased circulating percentages of BoCD2 lymphocytes, apparently due to changes in the BoCD4 subpopulation. The percentages of B cells were greatest in calves supplemented with alpha-tocopherol and Se. The results indicate that alpha-tocopherol and Se have interactive effects on lymphocyte responses to antigen and suggest that micronutrient status is important when interpreting the results of in vitro assays of lymphocyte function.

Animals↗

PubMed1994

Human cumulus cell complexes studied in vitro by light microscopy and scanning electron microscopy.

Various researchers describe the morphology of cumulus cells (CC) in vitro, but few have investigated their behaviour on plastic. Knowledge concerning the behaviour of human CC could be useful in improving the success of in vitro fertilisation procedures. This study aimed to describe the morphology and behaviour of CC in vitro and to investigate movement on a collagen-coated substrate. Following collection some cumulus were mechanically dissected from those surrounding the oocyte. Cumulus aggregates were cultured over 24 h using Earle's medium supplemented with 8% albumin. Substrata were plastic coverslips coated with collagens I, IV, or mixed collagens. Cumulus cultured over corresponding time periods on uncoated coverslips served as controls. Specimens were fixed and prepared for scanning electron microscopy. Over 24 h the controls began exhibiting the morphological features associated with cell movement: cell surface protrusions changed from blebs to microridges, lamellipodia and leading lamellae; cell shape altered from rounded and upright, to flattened. Extracellular matrix (ECM) transformed from a thick, sheet-like substance to a thin, fibrous material. By 24 h, cells contacting ECM remained rounded showing few features of movement. Collagens enhanced attachment of CC as a monolayer on the substrate. Cell morphology varied according to the collagen type used. On mixed collagens, cells attached rapidly, appearing to be predominantly non-motile. On collagen type I there was less attachment of cells but increased motility. On collagen type IV there was decreased attachment and the cells remained spherical. In conclusion, collagens enhance the settling of cumulus cells on a plastic substrate and the cells exhibit some specificity in attaching to collagens.

Adult↗

PubMed1994

Cobalt-vitamin B12 deficiency causes accumulation of odd-numbered, branched-chain fatty acids in the tissues of sheep.

Nine 5-month-old lambs were randomly allocated to two groups and were fed on either a Co-deficient whole-barley diet (n5), or the same diet supplemented with Co (n4). The lambs were fed on their respective diets for 28 weeks. Plasma vitamin B12 concentrations fell below the lower limit of normality after 6 weeks, and plasma methylmalonic acid (MMA) concentrations rose above the upper limit of normality after 10 weeks. However, plasma MMA concentrations fell to near normal levels towards the end of the experiment suggesting that diagnosis of more severe Co deficiency based on determination of plasma MMA concentrations may be of limited value. Analysis of tissue samples collected at slaughter revealed a marked reduction in the vitamin B12 concentration and the activity of methylmalonyl-CoA mutase (EC5.4.99.2) in the tissues taken from the Co-deficient sheep, by comparison with the controls. Although tissue concentrations of MMA in the Co-deficient animals were not significantly different from those of the controls, we did detect increased concentrations of branched-chain fatty acids. This suggested that misincorporation of MMA, but not propionic acid, into fatty acids had occurred. The Co-deficient lambs did not develop any neurological signs, suggesting that accumulation of branched-chain fatty acids may not be involved in the development of neurological lesions.

Animals↗

PubMed1994

Glucocorticosteroids up-regulate human elastin gene promoter activity in transgenic mice.

Recent characterization of the human elastin gene identified three putative glucocorticoid responsive elements (GRE) within the 5'-flanking DNA. To test the functionality of these cis-elements, transgenic mice that express a human elastin promoter-reporter gene (CAT) construct in a tissue-specific manner were injected with triamcinolone acetonide (TMC) or dexamethasone (DEX), two glucocorticosteroids in clinical use. Subcutaneous injection of these glucocorticoids resulted in a marked, up to 28-fold, enhancement of the CAT activity in the skin at the site of injection. Similarly, intraperitoneal injection of DEX resulted in significant increases in the elastin promoter activity in various internal organs. Furthermore, incubation of skin fibroblast and aortic smooth muscle cell cultures established from the transgenic animals with TMC (10 ng/ml) resulted in marked increases in the elastin promoter activity. These studies demonstrate that glucocorticosteroids act as powerful up-regulators of human elastin promoter activity in transgenic mice.

Animals↗

PubMed1994

Transient diabetes insipidus and acute fatty liver of pregnancy.

OBJECTIVE: To review the association of transient diabetes insipidus and acute fatty liver of pregnancy. DESIGN: A retrospective study. SETTING: Six women presenting with polyuria and polydipsia in the third trimester or in the immediate postpartum period, referred over a two and a half year period; five out of six were primigravida. All had raised liver transaminases and biopsy-proven acute fatty liver of pregnancy. Four out of six also had pre-eclampsia. SUBJECTS: Tertiary referral centre. MAIN OUTCOME MEASURES: There were no maternal deaths and only one fetal death. Desamino-cys-1-D-arg-8-vasopressin administration produced a reduction in urine output in all five women to whom it was administered. In all cases symptoms had resolved by the end of the fourth postpartum week. Three of the women have had subsequent pregnancies uncomplicated by either transient diabetes insipidus or acute fatty liver of pregnancy. CONCLUSIONS: The association of transient diabetes insipidus and acute fatty liver of pregnancy appears more common than previously recognised. Both may be part of the spectrum of pre-eclampsia.

Acute Disease↗

PubMed1994

Effects of the disruption of transmethylation in the central nervous system: an animal model.

INTRODUCTION: Central nervous system (CNS) methyltransferases methylate a wide range of substrates including proteins, lipids, nucleic acids and hormones. In every instance the methyl donor is S-adenosylmethionine (SAMe) and the demethylated product is S-adenosylhomocysteine (SAH). Methylation can be disrupted when there is an inadequate supply of methionine synthase (following vitamin B12 deficiency or folate deficiency), SAMe synthetase (due to ethanol), or SAH hydrolase (for unknown reasons). MATERIAL AND METHODS: 5-week-old pigs were maintained in an environment of either air or nitrous oxide, which inhibits methionine synthase, and were fed either a methionine-unsupplemented or methionine-enriched diet. After 3 to 10 weeks, pigs were killed by pentobarbitone injection and the levels of methionine and SAMe in the pigs' brain, spinal cord, plasma, liver, and kidney assessed. RESULTS: Pigs maintained in nitrous oxide displayed a dramatic fall in methionine levels in plasma and brain tissues but maintained relatively normal SAMe levels in these tissues. Brain and spinal cord cystathionine levels were markedly elevated, especially in those animals receiving oral methionine, as in the absence of methionine synthase homocysteine can be metabolized only through the catabolic pathway to cystathionine and cysteine. CONCLUSION: Disorders such as vitamin B12 deficiency or folate deficiency inhibit methylation by limiting the availability of SAMe or by elevating levels of the inhibitor SAH. In either case, the disruption of a wide range of methylation reactions can cause clinical sequelae ranging from structural abnormalities such as myelopathy to functional abnormalities such as depression.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed1994

Morbilliviral disease in Atlantic bottlenose dolphins (Tursiops truncatus) from the 1987-1988 epizootic.

Lungs and lymph nodes of 79 Atlantic bottlenose dolphins (Tursiops truncatus) that died from 6 August 1987 to 16 April 1988 along the Atlantic coasts of New Jersey, Virginia, and Florida (USA) were examined histologically and were tested for the presence of morbillivirus antigen by an immunoperoxidase technique. Lung lesions included areas of interstitial pneumonia characterized by varying combinations of type II pneumocyte hyperplasia, interstitial fibroplasia and leukocytes, syncytia, and intranuclear and intracytoplasmic inclusion bodies. Fungal, bacterial, and mixed bacterial and fungal pneumonias were common. Lymphoid depletion, lymphocytolysis, syncytia, and intranuclear and intracytoplasmic inclusion bodies were present in lymph nodes. Morbillivirus antigen was detected in 42 (53%) of 79 dolphins examined. Based on histopathologic and immunocytochemical findings, we diagnosed morbillivirus-induced disease. This is the first report of disease caused by morbillivirus in bottlenose dolphins and in any cetacean species outside Europe.

Animals↗

PubMed1994

Morbilliviral disease in an Atlantic bottlenose dolphin (Tursiops truncatus) from the Gulf of Mexico.

A free-living adult female Atlantic bottlenose dolphin (Tursiops truncatus) found dead near Panama City, Florida (USA), had necrotizing and ulcerative tracheitis, suppurative and hemorrhagic pneumonia, and necrotizing myocarditis; fungal hyphae were present in these lesions. Additionally, lungs had multifocal proliferative interstitial pneumonia with occasional syncytial cells. Some syncytial cells and type II pneumocytes contained eosinophilic intranuclear or intracytoplasmic inclusion bodies, or both. Based on an immunoperoxidase technique, there was morbilliviral antigen within cytoplasm and nuclei of type II pneumocytes and syncytial cells: antigen also occurred in trachea, skin, liver, stomach, intestine, and uterus. Based on pathologic and immunocytochemical findings, the dolphin had morbillivirus-induced disease. This is the first report of morbilliviral disease in a marine mammal from the Gulf of Mexico.

Animals↗

PubMed1994

Cobalt-vitamin B12 deficiency causes lipid accumulation, lipid peroxidation and decreased alpha-tocopherol concentrations in the liver of sheep.

A disease, known as ovine white liver disease (OWLD) was experimentally reproduced in lambs by feeding a diet depleted of cobalt. At necropsy, affected animals had pale, swollen, friable fatty livers, and showed marked accumulation of lipofuscin. Control animals, fed the same diet to which adequate amounts of cobalt had been added, were clinically normal. In animals with OWLD, liver triglyceride and free fatty acid concentrations were increased. A decrease in the ratio of phosphatidyl choline to phosphatidyl ethanolamine in the liver may result in a reduced ability to export triglycerides as very low density lipoprotein. This may cause the lipid accumulation characteristic of OWLD. Lipofuscin accumulation, another feature of OWLD, is a consequence of lipid peroxidation. Evidence for a peroxidative challenge was provided by the finding of reduced concentrations of alpha-tocopherol, elevated concentrations of induced 4-hydroxynonenal, and decreased amounts of the most readily peroxidizable fatty acids in the liver of animals with OWLD, by comparison with controls. The initiator of the peroxidative challenge is unknown, but may be related to the finding of increased concentrations of homocysteine in the plasma of animals with OWLD.

Aldehydes↗

PubMed1993

A thermospray mass spectrometric assay for Fe-induced 4-hydroxynonenal in tissues.

A method is presented for the determination of 4-hydroxynonenal (HNE) in tissue homogenates following in vitro lipid peroxidation induced by iron (Fe++). HNE is measured as the pentafluorobenzyl oxime derivative using liquid chromatography thermospray mass spectrometry. In vitro metabolism of HNE via the glutathione/glutathione-S-transferase pathway was inhibited using iodoacetic and iodobenzoic acids. The assay has been used as an indicator of the peroxidizability of tissue samples from animals both adequate in and depleted of alpha-tocopherol. The concentrations of HNE produced in tissues taken from animals depleted of alpha-tocopherol were found to be up to 8 times higher than those taken from animals supplemented with alpha-tocopherol.

Aldehydes↗

PubMed1993

The pathology of experimental Mycoplasma californicum mastitis in ewes.

Mastitis was reproduced experimentally by inoculating the lactating mammary glands of 12 ewes with Mycoplasma californicum. Large numbers of mycoplasmas were recovered from the milk. The mastitis had a lobular distribution and was characterized in the early stages by degeneration of the secretory epithelium and intense leucocytic infiltration of alveolar and ductal lumina. Later there was widespread alveolar involution, and lymphohistiocytic infiltration and fibrosis of the interstitium. A monoclonal antibody-based immunohistochemical technique detected M. californicum antigen in alveolar and ductal lumina but not in epithelium or interstitial tissue. This report is the first description of the pathological features of M. californicum mastitis in ewes.

Animals↗

PubMed1993

Histological, histochemical and ultrastructural features of hyaline inclusions in hepatocytes of striped dolphins (Stenella coeruleoalba).

Many striped dolphins (Stenella coeruleoalba) which died in the recent morbillivirus epizootic in the Mediterranean Sea had hyaline inclusions in hepatocytes. We investigated the histological, histochemical and ultrastructural features of these inclusions in two affected dolphins. Histochemical tests indicated that they contained glycoprotein but not lipid. Ultrastructurally, they consisted of granular, moderately electron-dense material, bounded by a membrane. A central or eccentric core of highly electron-dense material was usually apparent. The inclusions were probably of lysosomal origin.

Animal Diseases↗

PubMed1993

Antioxidant enzyme activity in the muscles of calves depleted of vitamin E or selenium or both.

Feeding diets depleted of vitamin E and Se to cattle can induce a disease known as nutritional degenerative myopathy. It is believed that an increased peroxidative challenge in muscle is involved in the pathogenesis of this disease. A number of species can up-regulate the activity of some antioxidant enzymes, including glutathione reductase (EC 1.6.4.2), glutathione transferase (EC 2.5.1.18), glucose-6-phosphate dehydrogenase (EC 1.1.1.49), catalase (EC 1.11.1.6), and superoxide dismutase (EC 1.15.1.1), in an attempt to mitigate the effects of a peroxidative challenge. A 2 x 2 factorial study was set up to examine possible changes in the activities of these antioxidant enzymes in muscles of ruminant calves fed on diets low in either vitamin E or Se. Four groups of four calves each were fed on a basal diet of NaOH-treated barley which was supplemented with alpha-tocopherol or Se or both for a total of 50 weeks. Calves fed on diets depleted of vitamin E, but not those fed on diets low in Se, developed subclinical myopathy, as judged by increases in the activity of plasma creatinine kinase (EC 2.7.3.2), and had increased muscle concentrations of two indices of lipid peroxidation, namely thiobarbituric acid-reactive substances, with and without ascorbate activation. Feeding diets depleted of vitamin E and diets low in Se both increased muscle activities of glucose-6-phosphate dehydrogenase in heart, biceps and supraspinatus. This change may have occurred in an attempt to maintain intracellular pools of reduced glutathione. No other changes in antioxidant enzyme activity were observed.

Animals↗

PubMed1993

Total quality assurance and peer education.

To promote program quality assurance, the Office of Health Promotion and Education at Penn State University evaluated peer health educators' presentation skills. Professional staff and experienced peer educators used an instrument tested for interobserver reliability to evaluate effectiveness in three skill areas: knowledge, delivery, and sensitivity. Each skill was rated, using a 4-point Likert-type scale. Knowledge included measures of preparation, subject knowledge, and ability to respond to questions knowledgeably; delivery included measures of clarity of directions, pacing, and transitions, appropriate and challenging questions, cooperation with co-facilitators, and enthusiasm; and sensitivity included comfort level, establishing trust in the group, nonjudgmentalism, appropriate use of humor, and nonsexist/nonheterosexist language. The evaluation teams observed and reviewed 18 work-shops conducted by 24 peer educators. Of the 24 educators evaluated, only 4 scored below 85%, the threshold for acceptable performance, and most scored above 90% in competency. Once baseline data had been gathered, the professional staff established a requirement that peer educators who did not meet this threshold must conduct their next two presentations with experienced peer educators who had met or exceeded it, and that professional staff members should work with students individually to improve skill levels. Evaluation criteria and threshold rates are to be reviewed each year.

Health Education↗