Search PubMed⌕ Search

Biomedical subjects

S Kennedy

Publications and source records attributed to S Kennedy.

At least 127 records · Page 7Linked to original sources
PubMed1998

Semi-quantitation of urokinase plasminogen activator and its receptor in breast carcinomas by immunocytochemistry.

Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA acts in vivo by binding to a membrane receptor known as uPAR. In this study, uPA and uPAR levels were semiquantitated by immunocytochemistry in 36 primary breast carcinomas. Using monoclonal antibody HD-UK 1, uPA was detected both in stromal and in malignant cells. However, the predominant location was in the stromal cells. Using double-staining, cells containing uPA were also found to coexpress either cytokeratin (an epithelial cell marker) or more frequently KP1 (a macrophage/monocyte cell marker). With monoclonal antibody HD-uPAR 13.1, uPAR was localized principally to spindle- or macrophage-like stromal cells, especially when these cells surrounded invasive breast cancer. In contrast, uPAR was only rarely detected in cancer cells and was not detected in normal epithelia surrounding tumour or in areas of adenosis. uPA levels in both stromal and epithelial cells were significantly correlated with those for uPAR. We conclude that both uPA and its receptor are mostly present in stromal cells in invasive breast carcinomas. These results suggest that stromal cells collaborate with malignant cells to mediate metastasis.

Antibodies, Monoclonal↗
PubMed1998

Characterization of novel circovirus DNAs associated with wasting syndromes in pigs.

Porcine circovirus (PCV) was initially recognized as a contaminant of continuous pig kidney cell lines and was not thought to be pathogenic. Antibodies reactive to the cell culture isolate of PCV (PCV PK-15) are prevalent in the swine population worldwide. Recently, PCV PK-15-like antigen and nucleic acid were demonstrated in lesions associated with wasting syndromes in pigs in North America and Europe. Monoclonal antibodies raised to circoviruses isolated from pigs with wasting syndromes highlighted differences between these circoviruses and the PCV PK-15 cell culture isolate. This has led to speculation that a new pathogenic PCV may have emerged in the swine populations of several countries. We report the cloning and characterization of novel circovirus DNAs purified from virus isolates made from tissues of North American and European pigs with wasting syndromes. These North American and European circoviruses form a closely related group at the nucleotide sequence level (> 96% intra-group nucleotide sequence identity) but exhibit < 80% nucleotide sequence identity with the PCV PK-15 cell culture isolate. This report provides evidence for a new type of possibly pathogenic PCV. We propose that these new circoviruses should be referred to as PCV2 as opposed to the original PK-15 cell culture isolate, which should be referred to as PCV1.

Amino Acid Sequence↗
PubMed1998

Do gastrointestinal symptoms vary with the menstrual cycle?

This systematic review presents both the physiological and symptom-based studies which have explored gastrointestinal variation across the menstrual cycle. Understanding this variation may be helpful in identifying the origin of pelvic pain, particularly as the symptoms associated with causes, such as endometriosis, also vary across the cycle. One-third of otherwise asymptomatic women may experience gastrointestinal symptoms at the time of menstruation, and almost 50% of women with irritable bowel syndrome report a perimenstrual increase in symptoms.

Abdominal Pain↗
PubMed1998

Platelet derived growth factor and fibroblast growth factor basic levels in the vitreous of patients with vitreoretinal disorders.

AIM: To determine the potential role of basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) in the pathogenesis of proliferative vitreoretinopathy (PVR). METHODS: An enzyme linked immunosorbent assay technique was used to determine the quantities of bFGF and PDGF in 38 vitreous samples taken from patients undergoing trans pars plana vitrectomy (PPV) for a variety of vitreoretinal disorders. RESULTS: bFGF levels ranged from undetectable to 318.7 pg/ml. The mean concentration was 27.57 pg/ml. PDGF levels ranged from undetectable to 160 pg/ml, the mean concentration being 40.06 pg/ml. Eight of 13 patients with clinical evidence of retinal detachment (RD) and PVR had significantly elevated bFGF concentrations, whereas only one of 11 patients with RD and no PVR had detectable bFGF; seven of eight patients with RD and PVR had elevated PDGF concentrations in the vitreous, whereas all 10 patients with RD and no PVR had no detectable vitreous PDGF. Eight patients with vitreous haemorrhage had raised PDGF concentrations, and the levels were particularly high (> 120 pg/ml) in those two patients with active neovascularisation. Two out of nine patients with vitreous haemorrhage had raised bFGF levels. CONCLUSIONS: bFGF and PDGF concentrations are elevated in PVR even in the absence of vitreous haemorrhage, and not in patients with RD uncomplicated by PVR. This observation suggests that both cytokines may be involved in the pathogenesis of PVR.

Adolescent↗
PubMed1998

Diminished serotonin-mediated prolactin responses in nondepressed stroke patients compared with healthy normal subjects.

BACKGROUND AND PURPOSE: The purpose of this study was to use hormonal responsiveness to d-fenfluramine (d-FEN) challenge as a measure of central serotonin (5-HT) function in a comparative evaluation of serotonergic abnormalities between stroke patients and healthy elderly normal subjects to test the hypothesis that stroke may be associated with diminished serotonergic functioning. METHODS: Eight nondepressed medically stable stroke patients and 12 healthy volunteers completed a single-blind, placebo-controlled, fixed-order, crossover design challenge test with 30 mg of oral d-FEN. Baseline prolactin (PRL) and cortisol (CORT) and hormonal responses to d-FEN and placebo were measured at hourly intervals over a 4-hour period. Cardiovascular responses (pulse and blood pressure) and behavioral responses were also recorded at the same time points. RESULTS: The 2 groups were comparable in demographics, body weight, plasma drug concentration, and behavioral and CORT responses. A 3-way ANOVA for repeated measures showed group differences for baseline adjusted PRL responses (change of scores from baseline). Peak PRL responses (maximal PRL change from baseline scores after treatment with d-FEN) in nondepressed stroke patients were attenuated compared with healthy elderly subjects, suggesting diminished serotonergic responsiveness in stroke patients. CONCLUSIONS: The demonstrated serotonergic hypofunctioning poststroke may contribute to the high incidence of depressive disorders in stroke patients. Serotonergic agents may have a role in augmentation of stroke recovery.

Administration, Oral↗
PubMed1998

No effect of depression on [(15)O]H2O PET response to intravenous d-fenfluramine.

OBJECTIVE: Subnormal prolactin responses to the serotonin-releasing agonist fenfluramine occur in depression. Since many measures of serotonin pathology occur in depression, abnormal responses to fenfluramine may occur in brain structures other than the hypothalamic-pituitary axis. One study compared six depressed and six healthy subjects' responses to oral d,l-fenfluramine by assessing [18F]fluorodeoxyglucose uptake as detected by positron emission tomography (PET). That study showed several abnormalities within the cortex, and the authors concluded that low responsivity to d,l-fenfluramine is widespread in depression. In this study abnormalities in regional neuromodulation by serotonin in major depression were assessed with intravenous d-fenfluramine and [(15)O]H2O PET. METHOD: Changes in regional cerebral blood flow (CBF) were detected by using [(15)O]H2O PET after administration of intravenous d-fenfluramine to 13 depressed and 18 healthy women. The PET scans were done 20 and 5 minutes before and 20 and 35 minutes after d-fenfluramine administration. Differences between the depressed and healthy groups in change in regional CBF (mean postfenfluramine minus mean prefenfluramine) were analyzed by using statistical parametric mapping. RESULTS: There were no significant differences between depressed and healthy subjects; in fact, changes in regional CBF after intravenous d-fenfluramine were remarkably similar. CONCLUSIONS: Degrees of neuronal responsivity to d-fenfluramine are similar in depressed and healthy subjects. Differences between the previous and current findings may be accounted for by greater specificity of intravenous d-fenfluramine to serotonin release, timing of scans, paucity of suicidal subjects in the current study, or greater variance in regional CBF from direct vascular effects of serotonin.

Administration, Oral↗
PubMed1998

Submandibular salivary proteases: lack of a role in anti-HIV activity.

Whole human saliva contains a number of proteolytic enzymes, mostly derived from white blood cells and bacteria in the oral cavity. However, less information is available regarding proteases produced by salivary glands and present in salivary secretions. In the present study, we have analyzed submandibular saliva, collected without contaminating cells, and identified multiple proteolytic activities. These have been characterized in terms of their susceptibility to a series of protease inhibitors. The submandibular saliva proteases were shown to be sensitive to both serine and acidic protease inhibitors. We also used protease inhibitors to determine if salivary proteolytic activity was involved in the inhibition of HIV infectivity seen when the virus is incubated with human saliva. This anti-HIV activity has been reported to occur in whole saliva and in ductal saliva obtained from both the parotid and submandibular glands, with highest levels of activity present in the latter fluid. Protease inhibitors, at concentrations sufficient to block salivary proteolytic activity in an in vitro infectivity assay, did not block the anti-HIV effects of saliva, suggesting that the salivary proteases are not responsible for the inhibition of HIV-1 infectivity.

Anti-HIV Agents↗
PubMed1998

Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe.

Samples of lung, liver, kidney, pancreas, spleen, and lymph node from pigs with postweaning multisystemic wasting syndrome from California (USA) and samples of mesenteric lymph nodes from similarly diseased pigs from Brittany (France) were examined by light microscopy, in situ hybridization (ISH), and/or virus isolation. Whole genomic probes for porcine circovirus (PCV) and chicken anemia virus (CAV) were used for ISH. Tissue homogenate supernatants were inoculated onto PK/15 cells for virus isolation, and the presence of viral antigen and viral particles was verified by indirect immunofluorescence, ISH, and electron microscopy. Histologic examination of lung from pigs from California revealed interstitial pneumonia, alveolar epithelial hyperplasia, and basophilic nuclear and cytoplasmic inclusions in mononuclear cell infiltrates and various pulmonary epithelial cells. Granulomatous lymphadenitis with syncytial cells typified the lesions seen in the pigs from France. PCV-like nucleic acid was detected by ISH in lung, pancreas, lymph node, kidney, and liver in pigs from California. Positive signal was also obtained in lymph node sections from pigs from France. Probes for CAV were consistently negative. PK/15 cell cultures inoculated with lung preparations from diseased California pigs and mesenteric lymph node preparations from pigs from France had positive fluorescence by indirect staining for PCV using pooled polyclonal pig sera and hyperimmune rabbit serum and had variable staining with a panel of 7 monoclonal antibodies specific for cell culture contaminant PCV. PCV-like nucleic acid was also detected by ISH in cell cultures. Cytopathic effect was not observed. Electron microscopic examination of inoculated cell cultures revealed 17-nm viral particles morphologically consistent with PCV. No other virus particles were observed. Although genomic analysis for the definitive identification of these viral isolates remains to be done, the evidence provided strongly suggests that these tissue isolates are closely related to, although antigenically distinct from, the original PCV cell culture contaminant.

Animals↗
PubMed1998

Luteinized ovarian cysts in Mediterranean striped dolphins.

The morbillivirus epizootic during 1990 to 1992 in Mediterranean striped dolphins (Stenella coeruleoalba) off the Mediterranean coast of Spain diminished these populations directly through mortalities, and indirectly through loss of normal fecundity. High levels of polychlorinated biphenyls (PCB's) also were detected in stranded animals. In addition to high numbers of abortions during the epidemic, unusual cystic structures were noted in the ovaries of several morbillivirus-infected dolphins with high PCB levels. These structures were identified as multiple luteinized cysts from their gross and histomorphologic characteristics. No morbillivirus antigens were detected in the lesions by immunohistochemistry. Because luteinized cysts occur when ovulation is impeded, either an effect of morbillivirus or PCB's on hypothalamic/pituitary function or an effect of PCB's on ovarian responsiveness are proposed as pathogenic mechanisms. These cysts may impede population recovery from the epidemic if similar cysts occurred on surviving dolphins.

Animal Nutritional Physiological Phenomena↗
PubMed1998

The genetics of endometriosis.

Endometriosis is probably a complex trait, like diabetes, hypertension or asthma, which implies that the disease is caused by an interaction between multiple genes and the environment. This paper reviews the evidence, in both human and nonhuman primates, that supports the theory of a genetic basis to endometriosis. The OXEGENE study, which aims to identify susceptibility genes in endometriosis through linkage analysis, is also described. DNA is being collected from families containing at least two sisters with surgically confirmed revised American Fertility Society stage III and IV disease to carry out a genome-wide search for susceptibility genes. Candidate genes involved in galactose metabolism and dioxin detoxification are also being analyzed. The identification of genes conferring susceptibility to endometriosis may lead to a better understanding of disease etiology and, in time, improved therapeutic strategies and diagnostic methods.

Endometriosis↗
PubMed1997

Human submandibular saliva specifically inhibits HIV type 1.

Studies from a number of laboratories have shown the presence of factor(s) in whole, parotid, and submandibular human saliva capable of inhibiting HIV-1 infectivity in vitro. Data from our laboratory suggested that the level of anti-HIV-1 activity is higher in submandibular than parotid or whole saliva. Previous results obtained with pooled submandibular saliva from seronegative individuals included a filtration step following saliva-virus interaction. In this article, we present data on the HIV-1 inhibitory activity of individual submandibular saliva samples collected from 15 donors. We show that although anti-HIV activity is quantitatively similar in most individuals (9 of 15), some (4 of 15) are much less active than others and some (2 of 15) lack inhibitory activity. We also show that for most individuals the level of anti-HIV inhibitor is similar with or without a filtration step. However, 2 of the 15 samples demonstrated activity only after filtration. The quantitative and qualitative anti-HIV activity of individual saliva samples appeared to reflect differences in the individual donors. We further show that the anti-HIV activity of submandibular saliva is demonstrated not only against laboratory strains of HIV-1 but is similarly active against three clinical HIV-1 isolates. In contrast, submandibular saliva had little effect on the infectivity of HIV-2 or SIV.

Antiviral Agents↗
PubMed1997

Lipid peroxidation induced in vivo by hyperhomocysteinaemia in pigs.

Much attention has been focused recently on the relationship between homocysteinaemia and the development of premature atherosclerosis. Hyperhomocysteinaemia constitutes as strong a risk factor for the development of the disease as either hypercholesterolaemia or smoking. Although the mechanism involved is unclear homocysteine exhibits prooxidative activity in vitro. This finding suggests that it may be involved in the oxidative modification of low density lipoprotein (LDL). In the current study hyperhomocysteinaemia was induced in eight domestic pigs by intermittent exposure to nitrous oxide for 4 weeks. At necropsy, cardiac tissue was removed and malondialdehyde (MDA) and the unsaturated fatty acid content were measured and compared with values obtained from air-breathing control animals. Nitrous oxide treated animals had significantly higher tissue concentrations of MDA than the controls. There was also a reduction in the contribution of linoleic and linolenic acids to the total fatty acid content of heart. The hyperhomocysteinaemic animals also had a significantly higher iron concentration in the heart than controls. Hyperhomocysteinaemia was associated with elevations in tissue iron stores and increased in vivo lipid peroxidation.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1997

Lesions in the reproductive tract of boars experimentally infected with porcine rubulavirus.

"Blue eye" disease of pigs in Mexico is caused by porcine rubulavirus and characterized by infertility in sows and boars, nervous signs in young pigs, and corneal opacity in pigs of all ages. The pathogenesis of reproductive tract lesions in rubulavirus-infected boars has not previously been investigated. In a first experiment, four 9-month-old boars were inoculated with porcine rubulavirus and killed 5, 15, 30 or 45 days post-inoculation (pi). In a second experiment, four similar boars were inoculated with the same virus and two animals were killed on each of days 70 and 80 pi. Swelling of the head of the epididymis developed in all inoculated boars at approximately day 15 pi. Reduced spermatozoan motility and concentration were detected in semen samples collected from one boar from day 21 pi. At post-mortem examination, nodules were seen in the head of the epididymis of the boars killed 15, 30 or 45 days pi and the right testis of the pig killed 30 days pi was atrophic. Corresponding histopathological epididymal alterations included formation of spermatic granulomas and vacuolar degeneration of ductular epithelium. These lesions were associated with mononuclear cell infiltration and interstitial fibroplasia. Degeneration of seminiferous tubules and interstitial mononuclear cell infiltration were seen in the atrophic testis of the pig killed 30 days pi. There was fibrosis of the head of the epididymis in all boars killed 70 or 80 days pi and one of these animals also had right testicular atrophy associated with degeneration of seminiferous tubules, lymphocytic infiltration and giant cell formation. Porcine rubulavirus antigen was detected by immunofluorescence labelling in the head of the epididymis of the pigs killed 15, 30 or 45 days pi and in one animal killed on day 70 pi. These results indicate that porcine rubulavirus can cause severe epididymo-orchitis and reduced semen quality in sexually mature boars.

Animals↗
PubMed1997

Bovine viral diarrhoea virus infection in bone marrow of experimentally infected calves.

Colostrum-deprived calves were inoculated with either a field isolate of bovine viral diarrhoea virus (BVDV) containing cytopathogenic (CP) and noncytopathogenic (NCP) biotypes or with only the NCP biotype. Paraffin wax-embedded sections of bone marrow from these calves, examined by means of an immunoperoxidase method, showed BVDV antigen in megakaryocytes and myeloid cells. Infection of such cells may play a role in the pathogenesis of thrombocytopenia, leucopenia and neutropenia, as reported in cattle infected with BVDV.

Acute Disease↗
PubMed1997

Plasminogen activator inhibitor type 2 in breast cancer.

The serine protease urokinase plasminogen activator (uPA) is causally involved in cancer invasion and metastasis. Activity of this protease in vivo is controlled principally by two inhibitors, one of which is plasminogen activator inhibitor type 2 (PAI-2). In this study, we show that PAI-2 levels were significantly higher in primary breast carcinomas (n = 152) than benign breast tumours (n = 18). In the primary cancers, PAI-2 levels correlated weakly but significantly with those of uPA and PAI-1, but not with tissue type plasminogen activator (tPA) or uPA receptor (uPAR) levels. Using Northern blotting, mRNA for PAI-2 was found in 28.6% of 49 primary breast cancers. In contrast to findings at the protein level, PAI-2 mRNA levels failed to correlate with those for uPA or PAI-1. After immunocytochemistry with primary cancers, PAI-2 was detected predominantly in the malignant cells of primary carcinomas but was also present in stromal cells. Using the median value as a cut-off point, PAI-2 showed no significant relationship with either disease-free interval or overall survival. However, using an optimum cut-off value, patients with low levels of PAI-2 had a worse outcome than those with a high level. We conclude that, unlike PAI-1, high levels of PAI-2 may be a favourable prognostic marker in breast cancer.

Age Factors↗