Rabbit viral haemorrhagic disease in Northern Ireland.
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Biomedical subjects
Publications and source records attributed to S Kennedy.
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The expression of integrin subunits has been investigated in the stroma and epithelium of eutopic and ectopic endometrial tissues, using immunohistochemistry and fluorescently activated cell-sorting techniques. Integrin subunits exhibited tissue-specific expression in both eutopic and ectopic endometrium. Integrin alpha 3 subunit was up-regulated in ectopic endometrium compared with the eutopic counterpart, whereas alpha 6 integrin subunit was down-regulated in the ectopic tissues. Cycle stage-dependent expression of alpha v and beta 3, observed in eutopic endometrium, was absent in the ectopic counterpart. It is concluded that the development and regeneration of the endometrium involve complex integrin-ligand interactions and that regulation of specific adhesive events is lost in endometriosis.
OBJECTIVE: Recent consensus on the subclassification of the eating disorder bulimia nervosa into purging and nonpurging forms is examined in the context of a large psychiatric epidemiological survey in Ontario, Canada. METHOD: Among a sample of 8,116 individuals, 62 met criteria for bulimia nervosa. Of these, the 17 who were of the purging subtype could be distinguished from the nonpurging group on a variety of parameters of comorbidity, family history, and childhood environment. RESULTS: The purging subtype was distinguishable on the basis of early age of onset, and high rates of affective disorders and anxiety and alcoholism, sexual abuse, and parental discord. DISCUSSION: The data support the taxonomy and point to the need for better understanding of the meaning of purging behavior.
An understanding of how oncogenes affect differentiated liver functions might lead to improved treatments for liver cancer or other disorders where liver-specific functions are compromised. A retroviral vector that coexpressed beta-galactosidase (beta-gal) and activated Ras genes (Ras-gal) was transduced into a small fraction of adult rat hepatocytes in vivo. Hepatocytes from Ras-gal-transduced diethylnitrosamine-untreated livers and hepatocellular carcinomas (HCC) from Ras-gal-transduced diethylnitrosamine-treated rats were analyzed for liver functions by performing histochemical assays on liver sections. Ras-gal-transduced hepatocytes failed to express gluconeogenic, ketogenic, and urea pathway enzymes. In contrast, several enzymes involved in fat synthesis were strongly activated, and microvesicular fat accumulated. These metabolic changes are induced in normal livers by insulin, a hormone that activates p21-ras. The deregulation of p21-ras may inhibit these liver-specific functions and may induce fat synthesis in both malignant and nonmalignant liver diseases. Furthermore, treatment with drugs that inhibit the attachment of p21-ras to the plasma membrane might reverse these changes. The alterations in enzymatic functions in the HCCs were similar to those observed in the hepatocytes, although each of the two cancers had a region that abruptly lost its expression of liver-specific enzymes and acquired the expression of genes that are more characteristic of oval or bile ductule cells. This suggests that a single genetic event in a malignant cell may dramatically alter its apparent phenotype. The identification of this putative gene might lead to insights into the regulation of the phenotype of normal cells in the liver.
A method is described by which RNA, suitable for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, can be extracted from formalin-fixed paraffin-embedded (FFPE) tissues and subsequently used for detecting the expression of several genes. Using this technique, RNA can be extracted from specimens, quantified, reverse transcribed and regions of interest amplified and analysed within 36 h. The tissue specimens included in this study were from human breast carcinoma, investigating a range of genes associated with the development and/or maintenance of multiple drug resistance (MDR). This technique, applied to archival tissues, offers great potential for increasing our understanding of alterations in expression levels of genes associated with MDR. The method developed is also applicable to studies on expression of other genes in paraffin-embedded tissues.
Healthy premenopausal women with regular cycles are believed to be increasing or maintaining bone density. However, few studies have prospectively documented spinal cancellous bone, the bone that changes rapidly in response to reproductive hormones, in this population. Furthermore, our previous one-year study documented that 24% of the one-year bone change by quantitative computed tomography (QCT) was related to subclinical ovulatory disturbances (short luteal phase and non-ovulation) in the presence of regular menstrual cycles. The purpose of this study was to document the cancellous bone change over five years in this initially ovulatory, premenopausal cohort of 66 healthy women. Thirty-seven women, who continued to be premenopausal and have regular cycles, completed this five-year study. Those enrolled differed only by being older and weighing less than those who could not be contacted (n = 19) or who declined to participate (n = 10). Documentation of current ovulatory characteristics was obtained for at least three cycles in 27 women. At the five-year assessment, the volunteers were 40.6 (range 26-47) years old, weighed 58.5 (41-77) kg, and were 160.9 (149-174) cm in height. All were premenopausal, healthy, nonsmokers with regular menstrual cycles (mean 27.7, range 24-33 days). Six women with intervening events (such as pregnancy or use of oral contraceptives) had interval (12 to 60 months) QCT changes similar to the remaining 31 (-7.98 vs. -4.92 mg/cm, p = 0.1, respectively). Mean five-year QCT was 143.0 +/- 20.2 mg/cm, whereas the initial mean value was 151.9 +/- 20.1 mg/cm. Significant QCT loss over five years (-8.9 +/- 6.2 mg/cm) (95% Cl -6.9 to -11.0) correlated with QCT change in the first year (r = 0.629, p < 0.001). First-year change was not related to the subsequent four-year interval change (r = -0.056, p = 0.74), however. Five-year QCT change was not related to age, weight, osteoporosis family history, estimated calcium intake, or exercise, but did correlate with year one luteal index (luteal/cycle length) (r = 0.339, p = 0.043). Significant cancellous spinal bone loss occurs in healthy, ovulatory premenopausal women, and is influenced by subclinical disturbances of ovulation.
OBJECTIVE: To compare conventional two- (2-D) and three-dimensional (3-D) scanning of the uterine cavity with and without saline contrast medium. DESIGN: Observational pilot study. SETTING: University-based fertility service. PATIENT(S): Ten IVF patients requiring uterine cavity assessment. INTERVENTION(S): Two-dimensional and 3-D transvaginal scans before and after injection of saline into the uterine cavity. MAIN OUTCOME MEASURE(S): Number and type of uterine cavity abnormalities detected by each technique. RESULT(S): The 2-D scanning suggested cavity abnormalities in 4 of 10 women (fibroids, 3; hyperechoeic thick endometrium, 1). The 3-D scanning confirmed these and revealed one additional abnormality suggestive of a uterine septum. The 2-D scanning with saline injection diagnosed abnormalities in 5 of 10 (uterine septum, 1; fibroids, 3; endometrial polyp, 1). The 3-D contrast scanning with saline did not add any further information to 2-D contrast scanning with saline. CONCLUSION(S): In this pilot study, 3-D scanning to assess the uterine cavity appeared to offer no advantages over conventional 2-D contrast sonography.
Phosphorus 31 nuclear magnetic resonance spectroscopy as a non-invasive technique was applied to monitor the metabolic activity of the human placenta during perfusion in vitro. During control perfusions (n = 3) there was an initial increase in adenosine triphosphate (ATP) and a fall in inorganic phosphate (Pi). Thereafter, however, the level of both ATP and Pi remained constant throughout the perfusion period (11 h). Additional biochemical parameters such as glucose consumption, lactate production and the release of hormones, human chorionic gonadotrophin (hGC). measured in the perfusate samples, were also used to assess the viability of the placental tissue. As with ATP, all these biochemical parameters under the control conditions showed a stable rate of metabolic activity throughout the length of the experiments. In additional experiments, the effect of the metabolic inhibitor dinitrophenol (n = 2) and dinitrophenol (DNP) together with iodoacetic acid (IOA, n = 2) were studied. DNP (0.1 mM) alone showed a slight decrease of all parameters. In contrast, the addition of IOA (0.1 mM) with DNP (0.1 mM) not only blocked the production of ATP but also produced a substantial impact on placental metabolic activity. The effect of a toxic dose of cadmium (20 nmol/ml) was studied also (n = 3). This dose of cadmium demonstrated no effect on phosphorus metabolism. However, the rate of glucose consumption and the release of hCG were significantly reduced.
The aim of this study was to assess patient tolerance of two outpatient tests. Sixty-six infertile women were prospectively randomized to hysterosalpingo-contrast sonography (HyCoSy) (n = 34) or X-ray hysterosalpingography (HSG) (n = 32). The procedures were performed by the same operator. The uterine cavity outline and tubal patency were determined by both procedures. The mean times taken and the volume of contrast medium required for HyCoSy and HSG were similar: 12.1 +/- 5.2 and 9.5 +/- 4.8 min and 9.4 +/- 5.2 and 11.5 +/- 8.4 ml, respectively. Side-effects were assessed during the procedure, at 2 h, 24 h and 28 days. The most common side-effect was pelvic pain, in 56/66 (84%) women, occurring during the procedures (HyCoSy 19/34 (56%); HSG 23/32 (72/%)) and/or in the following 24 h (HyCoSy 14/34 (41%); HSG 15/32 (47%)). This was described as less severe or equal to their usual period pains (HyCoSy 100%; HSG 85%). Only 12/66 (18%) women required simple non-steroidal analgesia (HyCoSy 8/34 (24%); HSG 4/32 (13%)). There were no significant differences between the two methods concerning the frequency or severity of pains at different stages during and after the procedure or analgesia requirements. HyCoSy and HSG are equally well tolerated outpatient procedures for assessing tubal patency and uterine abnormalities. In addition, HyCoSy avoids the risks of ovarian irradiation and allows scanning of the uterine corpus and ovaries at the same time.
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We investigated the length of time between the onset of pain symptoms and the surgical diagnosis of endometriosis in women from the UK and the USA. A total of 218 women with surgically confirmed disease, recruited through endometriosis self-help groups, completed a postal questionnaire. The mean +/- SD delay in diagnosis for women from the USA was 11.73 +/- 9.05 years, significantly higher than the equivalent delay of 7.96 +/- 7.92 years for women from the UK (P < 0.01). The stage of disease did not effect the length of time between the onset of symptoms and diagnosis. Therefore there is considerable delay in the diagnosis of endometriosis for women from both the UK and the USA. Efforts to reduce this delay are required to minimize the suffering of women with this disease.
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Lung samples from pneumonic lesions in cattle and goats, naturally or experimentally infected with strains of the Mycoplasma mycoides cluster, were fixed in formalin and embedded in paraffin. An immunohistochemical technique using monoclonal or polyclonal antibodies was performed on tissue sections in order to detect Mycoplasma antigens. Four monoclonal antibodies (MAbs), one (2A3) raised against M. mycoides ssp. mycoides small colony (SC) and large colony (LC), two (1D3 and 5E5) against M. mycoides ssp. capri, and one (5A10) against M. bovis, were used. A range of polyclonal antibodies, raised to the individual subspecies of the M. mycoides cluster, and one to Pasteurella haemolytica, was also used. The MAb 2A3 showed positive immunostaining in lung sections from cattle and goats naturally and experimentally infected with M. mycoides ssp. mycoides SC and LC, but not with pneumonic lesions of cattle and goats due to other members of the M. mycoides cluster, M. bovis or Pasteurella spp. The MAb 1D3 showed immunostaining in lung sections from goats naturally and experimentally infected with M. mycoides ssp. capri, but again not with pneumonic lesions caused by other members of the M. mycoides cluster, M. bovis or Pasteurella spp. The MAb 5E5 immunoreacted in sections from pneumonic lesions from all animals infected with one of the three M. mycoides cluster subspecies used in the study, but not with M. bovis or Pasteurella infected tissue. Immunoreaction was mainly found in the cell debris around necrotic areas, as well as in macrophages, neutrophils and epithelial cells. The localization of antigens of the M. mycoides cluster using polyclonal antisera followed basically the same pattern as that obtained with the monoclonals. However, a wide cross reactivity was found between different antisera and relatively high background immunostaining was also seen, especially in necrotic areas. The results suggest that immunohistochemical methods using monoclonal antibodies are useful tools for the diagnosis and study of the pathogenesis of pneumonia caused by the Mycoplasmas of the M. mycoides cluster.
Progressive familial intrahepatic cholestasis (PFIC) occurs in many communities and races. A form of PFIC in five children from two consanguineous marriages in an Irish kindred is described. In addition, a review of clinical information from the records of three deceased members of the kindred strongly implies that they also suffered from PFIC. The children had a history of neonatal diarrhoea, sepsis, and intermittent jaundice that ultimately became permanent. They suffered intractable pruritus and growth retardation. Despite evidence of severe cholestasis, serum gamma-glutamyl transferase and cholesterol were normal in these children. Sweat sodium concentration were raised in three children. Liver histology showed severe intrahepatic cholestasis and hepatocellular injury. Urinary bile acid analysis revealed a non-specific pattern consistent with chronic cholestasis. These children suffer from a form of PFIC remarkably similar to that occurring in members of the Byler kindred.
AIMS/BACKGROUND: To identify an HLA association with pseudoexfoliation of the lens capsule to support the hypothesis that there is a genetic predisposition to pseudoexfoliation. A randomised trial would be ideal for establishing a relation but is more costly and time consuming to conduct. Case-control studies provide an alternative method of establishing a relation. METHODS: The study group comprised 128 subjects who presented to a major eye centre with pseudoexfoliation. Data from blood donors representative of the population of Ireland were used to form a control group. RESULTS: An HLA association with pseudoexfoliation is identified for 14 antigens. Eleven antigens (HLA A1, A33, B8, B47, B51, B53, B57, B62, DR3, DR12, and DR13) are significantly more common in the pseudoexfoliation group while three antigens (HLA B12, B17, and DR2) are significantly less common. Four HLA antigens are strongly associated, with odds ratios of over 7.5. CONCLUSION: The strength of this HLA association is supportive evidence for a genetic component to the development of pseudoexfoliation of the lens capsule.
Morbillivirus infection was diagnosed in 35/67 bottlenose dolphins (Tursiops truncatus) from the Gulf of Mexico that stranded from October 1993 through April 1994 in Alabama, Mississippi, and Texas (USA) during periods of increased dolphin strandings in each of the 3 states. Diagnosis was based on histologic lesions, immunohistochemical demonstration of mobilliviral antigen, and detection of morbilliviral RNA by a reverse transcriptase polymerase chain reaction (RT-PCR) test performed on formalin-fixed, paraffin-embedded tissue (5 dolphins), on histologic lesions and detection of morbilliviral RNA by RT-PCR performed on formalin-fixed, paraffin-embedded tissue (1 dolphin), and on detection of morbilliviral RNA by RT-PCR performed on unfixed lung samples collected from carcasses with advanced postmortem autolysis (29 dolphins). Histologic lesions included proliferative interstitial pneumonia with syncytial cells and eosinophilic intranuclear and intracytoplasmic inclusion bodies, lymphoid depletion and syncytial cells with eosinophilic intranuclear inclusion bodies in lymph nodes, eosinophilic intracytoplasmic inclusion bodies in transitional epithelium of urinary bladder, and a syncytial cell with eosinophilic intranuclear inclusion bodies in epidermis. Concomitant pulmonary aspergillosis was diagnosed histologically in 4 dolphins. This is the 5th reported morbilliviral epizootic of aquatic mammals and the 2nd involving bottlenose dolphins in the United States.
La Piedad Michoacan Paramyxovirus (LPMV) is a recently recognized paramyxovirus infecting pigs throughout Mexico. Disease syndromes observed in field cases associated with LPMV infection include neurologic, respiratory, and reproductive disorders. Clinical signs and the distribution of LPMV virus and antigen in tissue samples from pigs experimentally infected with LPMV by natural routes were studied. Severe neurologic disease and death occurred following experimental inoculation of 3- and 17-day-old pigs. All of the pigs inoculated at 3 days of age were either dead or moribund by 8 days after inoculation, whereas 30% of the pigs inoculated at 17 days of age were affected. Virus was consistently recovered from or demonstrated in tissues from the respiratory tract of both groups of pigs. LPMV and antigen were also demonstrated in central nervous system (CNS) tissues from these pigs; however, differences in virus distribution within the CNS were demonstrated in the 2 groups. In the pigs inoculated at 17 days of age, isolation of LPMV was restricted to the olfactory bulb and midbrain. In contrast, in the pigs inoculated at 3 days of age, isolation of LPMV was more widespread throughout the CNS tissue examined. Virus excretion studies indicated that nasal spread of LPMV was more important than fecal spread. Comparatively large quantities of infectious LPMV were consistently recovered from urine samples of experimentally infected pigs.
BACKGROUND: This study compares the characteristics of women with anorexia nervosa with those of women who have all the diagnostic features of that disorder except amenorrhoea. METHOD: The study uses data from a large community epidemiological survey of the mental health status of household residents in Ontario, Canada. A multi-stage stratified sampling design generated a sample of 4285 females aged 15-64. DSM-III-R diagnoses were made using the Composite International Diagnostic interview. RESULTS: Eighty-four out of 4285 female respondents met full or partial-syndrome criteria for anorexia nervosa. Comparison of these two groups revealed few statistically significant differences in terms of demographics, psychiatric comorbidity, family history or early experiences. CONCLUSIONS: Amenorrhoea did not discriminate between women with anorexia nervosa and women with all the features except amenorrhoea across a number of relevant variables. The authors question the utility of amenorrhoea as a diagnostic criterion.