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Biomedical subjects

S Kennedy

Publications and source records attributed to S Kennedy.

At least 19 recordsLinked to original sources
PubMed1995

Post mortem investigations on cetaceans found stranded on the coasts of Italy between 1990 and 1993.

Detailed pathological and virological examinations were carried out on 25 cetaceans found stranded between 1990 and 1993 on the coasts of six Italian regions (Latium, Tuscany, Apulia, Abruzzo, Veneto and Sicily). There were 16 striped dolphins (Stenella coeruleoalba), three bottlenosed dolphins (Tursiops truncatus), three Risso's dolphins (Grampus griseus), one rough-toothed dolphin (Steno bredanensis), one fin whale pup (Balaenoptera physalus), and one minke whale (Balaenoptera acutorostrata). Apart from parasitic diseases (44 per cent), the most frequently detected lesions were pneumonia (68 per cent), enteritis (44 per cent), non-purulent hepatitis (40 per cent), interstitial nephritis (32 per cent) and encephalitis (32 per cent). Morbilivirus infection was diagnosed by immunocytochemistry in four striped dolphins, two stranded on the coasts of Latium in 1991 and two on the coasts of Tuscany in 1993. Despite the presence of lesions consistent with morbilliviral pneumonia in two other striped dolphins stranded on the coast of Apulia in 1991, no morbillivirus antigen was demonstrated in the tissues of these animals. Anticanine distemper virus antibodies were detected in the serum of the adult minke whale found stranded on the coast of Tuscany in 1993. However, no viruses were isolated from the tissues of any of the 25 cetaceans.

Animals↗
PubMed1995

Familial endometriosis.

PURPOSE: The study aimed to identify families with endometriosis and to document disease severity within the families and the clinical characteristics of the affected women. RESULTS: Two hundred and thirty women with surgically confirmed endometriosis in 100 families were identified. The families consisted of 19 mother-daughter pairs, 1 set of cousins and 56 sister pairs. There were 5 families with 3 affected sisters, 1 family with 5 affected sisters, and 18 families with > or = 3 affected members in more than one generation. The mean age at the onset of symptoms and the mean age at surgical diagnosis was 22.1 +/- 8.8 SD (range 10-46) and 31.8 +/- 7.9 SD (range 15-56) years respectively. Seventy-nine women (34.3%) had revised AFS Stage I-II disease, and 151 (65.7%) had revised AFS Stage III-IV disease. CONCLUSION: The study confirms a familial tendency for endometriosis and supports the hypothesis that endometriosis has a genetic basis.

Australia↗
PubMed1995

An abnormal methylation ratio induces hypomethylation in vitro in the brain of pig and man, but not in rat.

1. The ratio of the methyl donor, S-adenosylmethionine, to the co-product, S-adenosylhomocysteine (the methylation ratio) is known to control the activity of methyltransferases in tissues. Inactivation of the vitamin B12-dependent enzyme, methionine synthase, reduces the methylation ratio in rats and pigs in vivo. 2. We have determined the effect that such alterations have on neural protein 'O' and 'N' methyltransferases using an in vitro assay in rats, pigs and humans in the presence of the normal methylation ratio and the abnormal methylation ratios found experimentally in vivo in rats and pigs. 3. The methylation ratio found in the neural tissues of vitamin B12-inactivated pigs significantly inhibits the protein methyltransferases of pigs and humans. 4. By contrast, the altered methylation ratio found in vitamin B12-inactivated rats only marginally inhibits the equivalent rat methyltransferases. 5. This is consistent with the induction of a myelopathy by such treatment in pigs and humans, but not in the rat. 6. Dietary supplements of methionine given to vitamin B12-inactivated pigs have been shown to prevent the myelopathy in vivo by both elevating the neural S-adenosylmethionine level and resetting the methylation ratio. We find in our in vitro assay that these events reinstate the methyltransferase activity to near normal levels, thus explaining its protective effect in vivo.

Animals↗
PubMed1995

Demonstration of hypomethylation of proteins in the brain of pigs (but not in rats) associated with chronic vitamin B12 inactivation.

1. Pigs treated with nitrous oxide for periods of 1, 2 and 4 months demonstrated markedly reduced levels of methionine synthase and concomitant reduction in the ratio of S-adenosylmethionine to S-adenosylhomocysteine, the methylation ratio, at all time intervals. 2. Both 'O' and 'N' methylations were significantly reduced in pigs after 4 months in nitrous oxide but not after shorter periods. 3. Hypomethylation correlated with the development of clinical ataxia, but was absent when the pigs were clinically normal. It also only occurred when the S-adenosylmethionine level fell. 4. Rats maintained in nitrous oxide for 4 months showed a marked reduction of methionine synthase but no reduction in the methylation ratio or in brain hypomethylation. None of the rats became clinically ataxic. 5. Using an exogenous protein as a methyl group acceptor, it was demonstrated in an in vitro assay that the methyltransferase enzymes responsible for brain 'O' and 'N' methylation were not affected per se by nitrous oxide treatment. 6. It is concluded that reduction of the methylation ratio in the brain of pigs as a consequence of methionine synthase inhibition leads to brain hypomethylation. This hypomethylation could affect critical components of nerve tissue, inducing the vacuolar myelopathic changes seen in the spinal cord of these animals, which mimic those of subacute combined degeneration in man.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1995

Lipid peroxidation, prostacyclin and thromboxane A2 in pigs depleted of vitamin E and selenium and supplemented with linseed oil.

In a 2 x 2 balanced factorial experiment the biochemical effects on pigs of two dietary factors were investigated. The first factor was alpha-tocopherol and Se supplementation and the second factor was supplementation with alpha-tocopherol-stripped linseed oil. In pigs fed on diets depleted of alpha-tocopherol and Se, increases in concentrations of markers of lipid peroxidation (4-hydroxynonenal and hexanal) were observed. However, skeletal myopathy was only observed in those pigs fed on diets depleted of alpha-tocopherol and Se and supplemented with oil. In those pigs, increased lipid peroxidation was observed in heart and supraspinatus muscle. The plasma concentration of thromboxane B2 was increased in pigs fed on diets depleted of alpha-tocopherol and Se, suggesting an increased tendency towards platelet aggregation. However, this change was reversed in pigs depleted of alpha-tocopherol and Se, but supplemented with oil. This may have been a consequence of loss of arachidonic acid, the substrate for thromboxane formation, as a result of lipid peroxidation.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Toxicity of Streptococcus pneumoniae in neurons, astrocytes, and microglia in vitro.

The toxicity of pneumococci and endotoxin in primary cultures of rat neurons, astrocytes, and microglia and in a human astrocyte and two human glial cell lines was determined. Heat-inactivated, rough pneumococci (up to 10(8) cfu/mL) or their cell wall (up to 50 micrograms/mL) produced dose-dependent toxicity after 48 h in microglial cells and to a lesser extent in astrocytes but not in neurons. Toxicity was similar for equivalent doses of heat-inactivated organisms and pneumococcal cell wall, but time-course experiments showed significant differences between the two stimuli. Endotoxin at concentrations of up to 5 micrograms/mL did not induce significant toxicity in any of the cells. Thus, pneumococci can induce toxicity in two brain cell types, microglia and astrocytes, and the pneumococcal cell wall appears to mediate toxicity. Direct toxic effects of bacteria on brain cells may in part be responsible for brain injury during meningitis.

Animals↗
PubMed1995

Bulimia nervosa in a Canadian community sample: prevalence and comparison of subgroups.

OBJECTIVE: Previous epidemiological studies of bulimia nervosa have generated differing estimates of the incidence and prevalence of the disorder. These differences are attributable, in part, to varying definitions of the illness and a range of methodologies. The authors sought to define the prevalence of bulimia nervosa in a nonclinical community sample, examine the clinical significance of DSM-III-R threshold criteria, and examine comorbidity. METHOD: Subjects across Ontario (N = 8,116) were assessed with a structured interview, the World Health Organization Composite International Diagnostic Interview, with specific questions added for bulimia nervosa. Subjects who met DSM-III-R criteria for bulimia nervosa were compared with those who were missing only the frequency criterion (two or more binge-eating episodes per week for 3 months). RESULTS: In this sample, the lifetime prevalence of bulimia nervosa was 1.1% for female subjects and 0.1% for male subjects. The subjects with full- and partial-syndrome bulimia nervosa showed significant vulnerability for mood and anxiety disorders. Lifetime rates of alcohol dependence were high in the full-syndrome group. Rates of parental psychopathologies were high in both bulimic groups but tended to be higher in the subjects with full-syndrome bulimia nervosa. Both bulimic groups were significantly more likely to experience childhood sexual abuse than a normal female comparison group. CONCLUSIONS: This study confirms other prevalence estimates of bulimia nervosa and its comorbid diagnoses from studies that were based on sound methodologies. It also points to the arbitrary aspects of the frequency of binge eating as a diagnostic threshold criterion for the disorder.

Adolescent↗
PubMed1995

Experiments in transgenic mice show that hepatocytes are the source for postnatal liver growth and do not stream.

One hypothesis is that postnatal liver growth involves replication of mature hepatocytes, which have an unlimited proliferative potential. An alternative viewpoint is that only certain periportal cells can replicate extensively and that daughter cells stream slowly from the periportal to the pericentral region of the liver. Transgenic mice expressing the beta-galactosidase (beta-gal) gene from the human alpha 1 antitrypsin promoter were used to examine the proliferative potential of hepatocytes. Surprisingly, only 10% of hepatocytes in two different transgenic lines stain blue with X-gal. In neonatal animals, singlets or doublets of expressing cells are randomly scattered throughout the liver. Although the overall frequency of blue cells is similar in older animals, these cells are present in much larger clusters, suggesting that individual expressing cells have replicated to form a clonally derived cluster. Expression patterns are not altered by the administration of an acute phase stimulus or by the performance a partial hepatectomy, suggesting that the expression state cannot be easily altered, and making it more likely that the expression state is indeed fixed. These results suggest that the clusters of blue cells are clonally derived in the transgenic mice. They argue that the parenchymal hepatocyte is responsible for growth in the postnatal liver and that streaming of liver cells does not occur.

Acute-Phase Proteins↗
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↗