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Biomedical subjects

K C Smith

Publications and source records attributed to K C Smith.

At least 37 records · Page 2Linked to original sources
PubMed2003

In vitro characterisation of high and low virulence isolates of equine herpesvirus-1 and -4.

Basic in vitro characteristics of high and low virulence isolates of equine herpesviruses-1 and -4 were investigated with particular reference made to the Ab4 and V592 isolates of EHV-1 as both have distinct endotheliotropism and clinical outcomes in pony challenge studies. Additionally, some EHV-4 isolates that showed variations in clinical outcome were included in some experiments. The aim of the study was to identify an in vitro characteristic that would differentiate strains of known virulence. Such a system could then be applied to vaccine and virulence studies as an effective screening tool. Viral growth kinetics in a variety of cell culture systems, plaque size, ability to replicate in fetal endothelium in organ culture, and sensitivity to acyclovir were compared. No reliable marker system that differentiated between higher and lower virulence isolates of EHV-1 and EHV-4 was identified.

Animals↗
PubMed2003

Bioinformatic analysis of autism positional candidate genes using biological databases and computational gene network prediction.

Common genetic disorders are believed to arise from the combined effects of multiple inherited genetic variants acting in concert with environmental factors, such that any given DNA sequence variant may have only a marginal effect on disease outcome. As a consequence, the correlation between disease status and any given DNA marker allele in a genomewide linkage study tends to be relatively weak and the implicated regions typically encompass hundreds of positional candidate genes. Therefore, new strategies are needed to parse relatively large sets of 'positional' candidate genes in search of actual disease-related gene variants. Here we use biological databases to identify 383 positional candidate genes predicted by genomewide genetic linkage analysis of a large set of families, each with two or more members diagnosed with autism, or autism spectrum disorder (ASD). Next, we seek to identify a subset of biologically meaningful, high priority candidates. The strategy is to select autism candidate genes based on prior genetic evidence from the allelic association literature to query the known transcripts within the 1-LOD (logarithm of the odds) support interval for each region. We use recently developed bioinformatic programs that automatically search the biological literature to predict pathways of interacting genes (PATHWAYASSIST and GENEWAYS). To identify gene regulatory networks, we search for coexpression between candidate genes and positional candidates. The studies are intended both to inform studies of autism, and to illustrate and explore the increasing potential of bioinformatic approaches as a compliment to linkage analysis.

Autistic Disorder↗
PubMed2003

An evaluation of diagnostic data in comparison to the results of liver biopsies in mature horses.

REASONS FOR PERFORMING STUDY: The diagnostic value of several investigative procedures commonly used during the evaluation of suspected equine hepatopathy cases has not been specifically quantified in previous studies. HYPOTHESIS: No noninvasive procedures would clearly discriminate between horses with and without significant liver disease. METHODS: Histopathology of biopsy samples was used as the 'gold standard' technique for definitive diagnosis of the presence or absence of significant liver disease. Clinical, ultrasonographic and clinicopathological data obtained during the investigation of 82 suspected cases of hepatopathy in mature horses were compared with the results of subsequent biopsy in order to quantify the diagnostic value of each test. RESULTS: Of the 82 cases, 61 were confirmed to have significant liver disease and 21 were not. Only serum concentrations of gamma-glutamyltransferase (gammaGT), globulins and alkaline phosphatase (AP) were found to be significantly different between the 2 groups of horses. Clinical and ultrasonographic abnormalities were found, when present, to be good indicators of the presence of liver disease. Certain single serum biochemical tests and combinations thereof were found to have high values for sensitivity (SN), specificity (SP), positive predictive value (PPV) and/or negative predictive value (NPV), but none showed high values for all 4 parameters leading to important limitations in their practical diagnostic application. Of all serum biochemical tests studied, the PPVs of only gammaGT and globulins could be clearly improved by considering especially high positive results. CONCLUSIONS: The single positive test results of greatest diagnostic value were presence of hepatic encephalopathy (HE), increased gammaGT, hyperglobulinaemia, hypoalbuminaemia, increased AP, increased total bile acids (TBA) and increased total bilirubin (TBil). Increased aspartate aminotransferase (AST) and increased glutamate dehydrogenase (GLDH) were also of good diagnostic value, but only when used in combination with the above tests. However, no single, combination or sequential test was able to discriminate fully between horses with and without biopsy-confirmed liver disease and reliance on the use of noninvasive tests for the prediction of the presence or absence of significant liver disease may lead to frequent diagnostic errors. Although certain positive results did reliably predict the presence of liver disease, negative test results were invariably poor predictors of the absence of liver disease. POTENTIAL RELEVANCE: Application of the findings in this study may not be directly applicable to other case populations. However, the results may help clinicians with their selection and interpretation of appropriate test results in cases of suspected liver disease.

Animals↗
PubMed2003

Retrospective analysis of historical, clinical, ultrasonographic, serum biochemical and haematological data in prognostic evaluation of equine liver disease.

REASONS FOR PERFORMING STUDY: Results of noninvasive tests of liver disease do not always correlate with the degree of hepatic disease nor outcome of the case. OBJECTIVE: To investigate the prognostic value of data collected using noninvasive tests during the investigation of cases of suspected liver disease in mature horses. HYPOTHESIS: Much of the data gathered during the investigation of suspected hepatopathy cases offers little prognostic guidance and interpretation of such data can be misleading. METHODS: The results from a range of common and noninvasive diagnostic techniques applied in 116 mature horses with suspected liver disease, were assessed for their ability to predict survival within a 6 month period. RESULTS: A significantly poorer prognosis was found in association with clinical signs suggestive of liver disease, presence of hepatic encephalopathy, ultrasonographic abnormalities, increased serum globulins, increased total bile acids (TBA), increased alkaline phosphatase (AP), increased gamma-glutamyl transferase (gammaGT), erythrocytosis, leucocytosis, low serum albumin and low serum urea. Additional significant novel findings of interest included an association between increased plasma fibrinogen and low serum creatinine concentrations with nonsurvival in cases of liver disease, an association between raised serum concentrations of AP and gammaGT with biliary hyperplasia and also an association between hepatic fibrosis, haemosiderosis and biliary hyperplasia with ultrasonographically detected hepatic abnormalities. CONCLUSIONS: The most useful noninvasive prognostic test in cases of suspected liver disease in mature horses is the severity of clinical signs. Other data may be of some limited prognostic value. POTENTIAL RELEVANCE: Application of the findings in this study may not be directly applicable to other case populations. However, the findings should at least be considered when prognosis is based on similar criteria.

Alkaline Phosphatase↗
PubMed2003

Detection of EHV-1 and EHV-4 in placental sections of naturally occurring EHV-1- and EHV-4-related abortions in the UK: use of the placenta in diagnosis.

REASONS FOR PERFORMING STUDY: EHV-1 and EHV-4 abortion diagnosis is based upon detailed examination of the aborted fetus. However, in some cases, only the placenta is available for examination. Furthermore, the contribution of lesions in the placenta to pathogenesis and diagnosis of EHV-1 and EHV-4 abortion has been neglected. OBJECTIVES: To assess the utility of placental examination in equine herpesvirus-1 (EHV-1) and EHV-4 abortion diagnosis. METHODS: Sections of allantochorion from 49 herpesvirus abortions were analysed by PCR, in situ hybridisation and immunostaining. RESULTS: Virus-specific nested PCR confirmed the presence of viral DNA in 46 cases; 41 cases were EHV-1-positive and 5 EHV-4-positive. Microscopic changes were nonspecific. Examination of the PCR-positive sections of allantochorion revealed EHV-1 DNA by in situ hybridisation (ISH) in 21 cases and EHV-4 in 4 cases. In 2 samples, DNA of both viruses was present on PCR and ISH. Viral antigen was found by immunohistology in 15 cases. Regarding the localisation of virus in the placentae, both viral DNA and antigen of EHV-1 and EHV-4 were found in endothelial cells of chorionic villi and, occasionally, in trophoblast epithelium. In the stromal endothelium, only EHV-1 was found. CONCLUSIONS: The data indicate that examination of placentae is a useful diagnostic aid in EHV-1 and EHV-4 abortion diagnosis. POTENTIAL RELEVANCE: Virological examination of the placenta should become standard practice in equine abortion investigations, particularly in those cases where the fetus is not available for examination.

Abortion, Veterinary↗
PubMed2003

A survey of equine abortion, stillbirth and neonatal death in the UK from 1988 to 1997.

REASONS FOR PERFORMING STUDY: A detailed review of laboratory records for equine abortion is fundamental in establishing current disease trends and suggesting problems important for further research. OBJECTIVES: To review the causes of abortion and neonatal death in equine diagnostic submissions to the Animal Health Trust over a 10 year period. METHODS: The diagnoses in 1252 equine fetuses and neonatal foals were reviewed and analysed into categories. RESULTS: Problems associated with the umbilical cord, comprising umbilical cord torsion and the long cord/cervical pole ischaemia disorder, were the most common diagnoses (38.8%: 35.7% umbilical cord torsion and 3.1% long cord/cervical pole ischaemia disorder). Other noninfective causes of abortion or neonatal death included twinning (6.0%), intrapartum stillbirth (13.7%) and placentitis, associated with infection (9.8%). E. coli and Streptococcus zooepidemicus were the most common bacteria isolated. Neonatal infections not associated with placentitis accounted for 3.2% of incidents; and infections with EHV-1 or EHV-4 for 6.5%. CONCLUSIONS: Definitive diagnosis of equine abortion is possible in the majority of cases where the whole fetus and placenta are submitted for examination. POTENTIAL RELEVANCE: Given the high incidence of umbilical cord torsion and related problems as causes of abortion in UK broodmares, more research on factors determining umbilical cord length and risk of torsion is essential.

Abortion, Veterinary↗
PubMed2001

A disease by any other name: musings on the concept of a genetic disease.

What exactly is a genetic disease? For a phrase one hears on a daily basis, there has been surprisingly little analysis of the underlying concept. Medical doctors seem perfectly willing to admit that the etiology of disease is typically complex, with a great many factors interacting to bring about a given condition. On such a view, descriptions of diseases like cancer as genetic seem at best highly simplistic, and at worst philosophically indefensible. On the other hand, there is clearly some practical value to be had by classifying diseases according to their predominant cause when this can be accomplished in a theoretically satisfactory manner. The question therefore becomes exactly how one should go about selecting a single causal factor among many to explain the presence of disease. When an attempt to defend such causal selection is made at all, the standard accounts offered (Koch's postulates, Hill's epidemiological criteria, manipulability) are all clearly inadequate. I propose, however, an epidemiological account of disease causation which walks the fine line between practical applicability and theoretical considerations of causal complexity and attempts to compromise between patient-centered and population-centered concepts of disease. The epidemiological account is the most basic framework consistent with our strongly held intuitions about the causal classification of disease, yet it avoids the difficulties encountered by its competitors.

Causality↗
PubMed2001

Molecular cytogenetic analysis of a novel high-grade canine T-lymphoblastic lymphoma demonstrating co-expression of CD3 and CD79a cell markers.

We present the molecular cytogenetic analysis of a novel case of canine lymphoma, in a nine-year-old entire male collie cross retriever dog that presented with an enlarged prescapular lymph node. A diagnosis of high-grade lymphoblastic lymphoma was made by histological evaluation of fixed lymph node biopsy sections, whilst immunohistochemical analyses demonstrated co-expression of B- and T-cell antigens (CD79a and CD3) by 95% of lymphomatous cells. Comparative genomic hybridisation (CGH) analysis detected loss of dog chromosomes 11, 30 and 38 and gain of chromosome 36 within the lymphoma biopsy specimen. These findings correlated with direct cytogenetic analysis of tumour metaphases using whole chromosome paint probes representing each of these four chromosomes. This study represents the first report of the combined application of both direct and indirect cytogenetic techniques for the analysis of recurrent chromosome aberrations in canine cancer.

Animals↗
PubMed2001

A study of the pathogenesis of equid herpesvirus-1 (EHV-1) abortion by DNA in-situ hybridization.

The polymerase chain reaction and DNA in-situ hybridization were used to study sections of uterine tissue collected from mares near the time of abortion due to equid herpesvirus-1 (EHV-1) infection. These techniques revealed viral nucleic acids in endothelial cells of endometrial arterioles, in accordance with previously published immunohistological data. In addition, however, they revealed nucleic acids in cellular debris within endometrial glands and diffusing across the placenta at sites of microcotyledonary infarction. Perivascular leucocytes were generally negative for viral DNA, despite marked perivascular cuffing. These data provided further support for the central role of the vascular endothelial cell in the pathogenesis of EHV-1 abortion and demonstrated direct transplacental spread of nucleic acids at sites of microcotyledonary infarction and across the endometrial glands in the vicinity of vascular lesions.

Abortion, Septic↗
PubMed2001

Inter-relationships among gonadotrophins, reproductive steroids and inhibin in freemartin ewes.

Freemartins are sterile XX/XY chimaeras that occur as a result of placental fusion between male and female fetuses during early pregnancy. Freemartins occur predominantly in cattle, although the prevalence of ovine freemartinism is increasing. In this study, the reproductive endocrinology of ovine freemartins was compared with that of normal sheep. Freemartins had significantly (P < 0.001) higher basal concentrations of LH and FSH than did normal ewes or rams, although the response of LH to GnRH (10 microg) was similar in freemartins, ewes and rams. Resting concentrations of oestradiol were similar in freemartins and ewes and were increased in both after eCG administration. Testosterone concentrations were higher in freemartins than in ewes, but were unresponsive to GnRH or eCG. Administration of 62.5 mg progesterone or 25 lg oestradiol twice a day for 3 days suppressed LH concentrations to baseline values in freemartins, ewes and rams. In ewes, 500 microg oestradiol administered twice a day caused preovulatory surges in LH concentrations, but suppressed LH in freemartins to baseline values. Thus, LH secretion can potentially be regulated in freemartins by gonadal steroids. FSH concentrations in freemartins were not suppressed by doses of inhibin that were effective in ewes and rams. Therefore, freemartins behave in part like castrated animals, as they have high basal concentrations of LH and FSH, which can be stimulated by GnRH and suppressed by gonadal steroids. Conversely, inhibin does not suppress FSH concentrations in freemartins, and freemartins have circulating concentrations of steroids intermediate between those of castrated and normal animals.

Animals↗
PubMed2000

Anatomical, cytogenetic and behavioural studies of freemartin ewes.

The external phenotype and reproductive behaviour of 21 freemartin sheep and two male pseudohermaphrodite sheep were recorded with the aim of identifying any characteristics which might be used to predict a failure to breed. The size and shape of the vulva and clitoris, the length of the vagina, the size of the teats, the presence or absence of inguinal gonads, and the ultrasonographic characteristics of the inguinal gonads were recorded. A subjective assessment of the masculinity of each animal's body form was also made, and its behavioural responses to a virile ram and to an oestrus ewe were recorded. A number of physical and behavioural abnormalities were detected but the only consistent finding in all 23 animals was a short vagina which varied in length from 3.1 to 7.0 cm, compared with 10 to 14 cm in normal animals.

Animals↗
PubMed2000

Virulence of the V592 isolate of equid herpesvirus-1 in ponies.

The V592 strain of equid herpesvirus-1 (EHV-1), which was originally isolated from a fetus during an abortion epizootic, has proved to be of low virulence in infection studies. Five Welsh Mountain pony mares and one foal were challenged intranasally or by aerosol with this isolate, and monitored clinically and virologically. All six animals shed virus in nasopharyngeal mucus, and viraemia was recorded from day 7 post-infection (PI). Pathological investigations revealed mild rhinitis and bronchiolitis in the mares, with viral antigen expression in degenerating epithelial cells of the nasal mucosa and bronchioles, and in occasional monocytes in the respiratory tract-associated lymph nodes. Viral antigen expression was not detected in vascular endothelium of the mares, although vasculitis was seen to have affected small numbers of blood vessels in the dorsocaudal lung regions of a mare examined on day 10 PI. In the foal, respiratory lesions of a more localized nature included infection of vascular endothelium and associated vasculitis. The foal also had localized encephalitis affecting the olfactory lobes of the brain, with viral antigen expression in degenerating olfactory neurons and microglia. The data suggest that the relatively low virulence of strain V592 is associated with a lower degree of endotheliotropism than that shown by the highly virulent Ab4 and Army 183 isolates, and that this property is influenced by host immunity.

Animals↗
PubMed2000

Topical antipsoriatics.

Topical corticosteroids are important in psoriasis therapy. However, there are other worthwhile options available including tar, anthralin, tazarotene, calcipotriol, topical PUVA, and topical porphyrin derivatives. With growing public reluctance to use systemic medications, topical treatments for psoriasis could become increasingly important in the future.

Administration, Topical↗