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Biomedical subjects

C Haley

Publications and source records attributed to C Haley.

17 recordsLinked to original sources

Genetic diversity in European pigs utilizing amplified fragment length polymorphism markers.

The use of DNA markers to evaluate genetic diversity is an important component of the management of animal genetic resources. The Food and Agriculture Organisation of the United Nations (FAO) has published a list of recommended microsatellite markers for such studies; however, other markers are potential alternatives. This paper describes results obtained with a set of amplified fragment length polymorphism (AFLP) markers as part of a genetic diversity study of European pig breeds that also utilized microsatellite markers. Data from 148 AFLP markers genotyped across samples from 58 European and one Chinese breed were analysed. The results were compared with previous analyses of data from 50 microsatellite markers genotyped on the same animals. The AFLP markers had an average within-breed heterozygosity of 0.124 but there was wide variation, with individual markers being monomorphic in 3-98% of the populations. The biallelic and dominant nature of AFLP markers creates a challenge for their use in genetic diversity studies as each individual marker contains limited information and AFLPs only provide indirect estimates of the allelic frequencies that are needed to estimate genetic distances. Nonetheless, AFLP marker-based characterization of genetic distances was consistent with expectations based on breed and regional distributions and produced a similar pattern to that obtained with microsatellites. Thus, data from AFLP markers can be combined with microsatellite data for measuring genetic diversity.

Alleles↗

Genetical genomics in livestock: potentials and pitfalls.

Genetical genomics combines gene mapping and gene expression approaches to identify loci controlling gene expression (eQTLs) that may underlie functional trait variation. The combination of genomic tools has great potential to facilitate dissection of complex traits, but studies need careful design and interpretation. Here we explore both the potential and the pitfalls of this approach with illustrations from actual studies. There are now an appreciable number of studies in model species and even humans demonstrating the feasibility of genetical genomics. However, most studies are too limited in size and design to unlock the full potential of the approach. Limited statistical power of studies exacerbates the problem of detection of false-positive eQTL and some reported results should be interpreted with caution. As one approach to more successful implementation of genetical genomics, we propose to combine expression studies with fine mapping of functional trait loci. This synergistic approach facilitates the implementation of genetical genomics for species without inbred resources but is equally applicable to model species. These properties make it particularly suitable for livestock populations where many QTL are already in the public domain and potentially very large pedigreed populations can be accessed.

Animals↗

Randomised controlled trial of cognitive-behavioural therapy in early schizophrenia: acute-phase outcomes.

BACKGROUND: Cognitive-behavioural therapy (CBT) improves persistent psychotic symptoms. AIMS: To test the effectiveness of added CBT in accelerating remission from acute psychotic symptoms in early schizophrenia. METHOD: A 5-week CBT programme plus routine care was compared with supportive counselling plus routine care and routine care alone in a multi-centre trial randomising 315 people with DSM-IV schizophrenia and related disorders in their first (83%) or second acute admission. Outcome assessments were blinded. RESULTS: Linear regression over 70 days showed predicted trends towards faster improvement in the CBT group. Uncorrected univariate comparisons showed significant benefits at 4 but not 6 weeks for CBT v. routine care alone on Positive and Negative Syndrome Scale total and positive sub-scale scores and delusion score and benefits v. supportive counselling for auditory hallucinations score. CONCLUSIONS: CBT shows transient advantages over routine care alone or supportive counselling in speeding remission from acute symptoms in early schizophrenia.

Adult↗

True and false positive peaks in genomewide scans: The long and the short of it.

When performing a genome scan in linkage or linkage disequilibrium studies to detect loci underlying complex or quantitative traits, it is important to attempt to distinguish between true and false positives using the appropriate statistical methods. There has been some controversy in the literature regarding the use of the length of a positive peak, i.e., the length of a chromosome region displaying identity-by-descent in linkage studies among affected individuals or the length of a continuous chromosome region for which the test statistic is above a certain threshold. We show in this study, by reasoning and by simulation studies, that conditional on the strength of evidence for a locus affecting a trait of interest, i.e., conditional on the peak height of a test statistic, there is no information in the length of the peak. Our finding has implications for linkage and association studies.

Analysis of Variance↗

On-site, rapid HIV testing with same-day results and counseling.

BACKGROUND: New rapid HIV antibody tests have allowed provision of results and result-specific counseling on the day on initial visit, and have the potential to increase the efficiency of HIV counseling and testing. METHODS: To evaluate the use of rapid testing with same-day results in public clinics, the Single Use Diagnostic System HIV-1 rapid assay was used for a 3-month period at an anonymous testing clinic and a sexually transmitted disease (STD) clinic in Dallas, Texas. Non-reactive rapid test results were reported as HIV-negative. Reactive results were reported as 'preliminary positive'. These procedures were compared with standard testing during a baseline period, with respect to number of clients receiving results and post-test counseling, client satisfaction, counselor acceptance, cost and effectiveness at reducing HIV risk. RESULTS: Rapid testing resulted in an increase in the number of persons learning their serostatus: a 4% increase for uninfected and a 16% increase for infected clients at the Anonymous Testing Clinic; a 210% increase for uninfected patients and a 23% increase for infected patients at the STD clinic. Rapid testing resulted in a cost saving of US$ 11 per test in both the anonymous and STD clinics. Of those previously tested, 88% responded that they preferred the rapid test. In the year following initial HIV test, clients tested with rapid and standard procedures were equally likely to return to the clinic with a new STD (odds ratio, 0.97; 95% confidence interval, 0.7-1.4). CONCLUSIONS: Rapid, on-site HIV testing was feasible, preferred by clients, and, resulted in significant improvement in the number of persons learning their serostatus, without increasing the costs or decreasing the effectiveness of counseling and testing.

Counseling↗

K+ reabsorption by the lower Malpighian tubule of Rhodnius prolixus: inhibition by Ba2+ and blockers of H+/K+-ATPases

Active K+ reabsorption by the lower Malpighian tubule of the blood-feeding hemipteran Rhodnius prolixus does not involve the amiloride-sensitive K+/H+ exchangers or V-type H+-ATPases implicated in secretion of ions from haemolymph to lumen in the upper tubule. Amiloride, N-ethylmaleimide, 4-chloro-7-nitrobenzo-2-oxa-1,3-diazol and bafilomycin A1 inhibit haemolymph-to-lumen secretion of Na+ and K+ by the upper Malpighian tubule, but have little or no effect on lumen-to-haemolymph reabsorption of K+ by the lower tubule. The effects of inhibitors of H+/K+-ATPases, including omeprazole and SCH 28080, suggest that a pump similar to the H+/K+-ATPase of the gastric mucosa is involved in KCl reabsorption. The presence of K+ channels in the basolateral membrane in the lower Malpighian tubule is suggested by inhibition of KCl reabsorption by basolateral but not apical application of the K+ channel blocker Ba2+, and by blockade of K+-dependent changes in membrane potential by Ba2+. It is proposed, therefore, that K+ is pumped from lumen to cell by an ATP-dependent pump resembling the H+/K+-ATPase of the gastric mucosa, and that K+ leaks from cell to bathing saline (haemolymph) via an electrodiffusive pathway (i.e. K+ channels).

Journal Article↗

Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy.

OBJECTIVES: To determine the expression of prostate-specific membrane antigen (PSMA) before and after androgen-deprivation therapy and to compare PSMA expression with prostate-specific antigen (PSA) expression. METHODS: We studied specimens from 20 patients with prostate cancer undergoing medical or surgical castration or combination androgen-deprivation therapy in whom matched pretreatment and post-treatment tissue specimens were available and 16 patients in whom only a post-treatment specimen was available. The expression of PSMA and PSA in the tissue specimens was determined by immunoperoxidase staining. The extent of staining was calculated by multiplying the percent of antigen-positive tumor cells by the staining intensity to arrive at a stain index for each biomarker. An in vitro study assessed the concentration of PSMA and PSA in extracts of LNCaP cells cultured in the presence or absence of androgen as determined by immunoassays and Western blot analysis. RESULTS: PSMA reactivity was found to be increased in 55% (11 of 20) of post-treatment primary tissues and 100% (4 of 4) of post-treatment metastatic specimens. In contrast, PSA expression was found to be decreased in 70% (14 of 20) of post-treatment primary and 100% (4 of 4) of post-treatment metastatic specimens. Neither type of androgen-deprivation treatment nor tissue sensitivity to androgen deprivation appeared to influence degree of biomarker expression. PSMA was found to be downregulated and PSA upregulated when LNCaP cells were cultured in the presence of testosterone or dihydrotestosterone. CONCLUSIONS: The enhanced expression of PSMA in tissues and LNCaP cells after androgen deprivation suggests that PSMA is upregulated in the majority of prostate carcinomas after androgen treatment. The high expression in metastatic tissues strongly suggests that PSMA may be a clinically useful target for antibody-and genetic-directed therapy of prostate cancer that recurs after androgen deprivation. The mechanism whereby androgens suppress the expression of PSMA, and the association of PSMA with the development of hormone-independent prostate cancers, will require further study.

Androgen Antagonists↗

Alignment of the PiGMaP and USDA linkage maps of porcine chromosomes 2 and 5.

The PiGMaP and USDA porcine linkage maps for chromosomes 2 and 5 have been aligned by typing five USDA microsatellite markers from chromosomes 2 and 4 from chromosome 5 on the PiGMaP reference families. The markers in the two maps can be successfully aligned except for Sw395 on chromosome 2, which is the end-most marker in the USDA map 22 cM remote from the next marker, but which maps to a more central location and in the same position as Sw776 in the PiGMaP families. The mapping of four additional chromosome 5 markers has enabled amalgamation of the two previously separate PiGMaP linkage groups assigned to chromosome 5 and has more than doubled the length of its map. The USDA map of chromosome 5 is considerably shorter than the revised PiGMaP version, particularly between DAGK and Sw1071, where the corresponding lengths are 9 cM versus 33 cM.

Animals↗

Performance of a rapid, on-site human immunodeficiency virus antibody assay in a public health setting.

Rapid, on-site human immunodeficiency virus (HIV) testing has the potential to improve the delivery of prevention services in publicly funded counseling and testing sites. The Single Use Diagnostic System (SUDS) HIV-1 is the only rapid enzyme immunoassay (EIA) approved for diagnostic use in the United States. To evaluate the feasibility of using SUDS in public clinics and to validate the test's performance in a public health laboratory, we conducted blinded SUDS testing on plasma sent for HIV testing. From 19 March through 30 June 1993, 1,923 consecutive samples from a sexually transmitted diseases clinic and an HIV counseling and testing clinic were tested on site with SUDS. Tests done in the first two weeks with a malfunctioning centrifuge n = 402) and those done when there were excessively high temperatures in the laboratory (n = 53) were analyzed separately. Of 1,466 tests, 39 were positive by both SUDS and EIA (with Western blot [immunoblot] confirmation) and 7 were SUDS positive and EIA negative. Western blotting was used as the "gold standard" to adjudicate these discrepancies. There were no SUDS-negative and EIA-positive tests. Compared with that of EIA (with Western blot confirmation), the sensitivity of SUDS was 100% (95% confidence interval, 88.8 to 100%) and the specificity was 99.5% (95% confidence interval, 98.9 to 99.8%). The positive predictive value of SUDS was 88% in the STD clinic and 81% in the HIV counseling and testing clinic. There was a 7.7-fold increase in false positives, from 0.48 to 3.7%, when there was inadequate centrifugation and when the temperature exceeded the manufacturer's recommendations. Rapid, on-site HIV testing by the SUDS assay is feasible and practical in public health settings. The test can be performed accurately, at reasonable cost, and within the time frame of a typical clinic visit. Caution should be used, however, as two conditions adversely affected the accuracy of this test: inadequate specimen preparation and elevated temperature.

AIDS Serodiagnosis↗

Postoperative brainstem and cerebellar infarcts.

OBJECTIVE: To study the clinical features and causes of postoperative brainstem and cerebellar infarcts. METHODS: Two groups were studied. The 10 group 1 patients had cardiac (eight) or aortic (two) surgery. The 12 group 2 patients had noncardiac-nonvascular surgery, including orthopedic (five), gynecologic (four), and general (three). Patients were studied by stroke services at university hospitals in Boston (13), Charlottesville (three), Baltimore (three), and Mainz (three) during 2 consecutive years. RESULTS: Onset of strokes was immediately postoperative (six), during the first 48 postoperative hours (nine), and delayed 3 days or more (seven). Clinical syndromes were altered level of consciousness or cognition (15), vestibulocerebellar (four), and hemiparesis with focal brainstem signs (three). Infarction involved the brainstem (13), cerebellum (13), and posterior cerebral artery hemispheric territory (10). Causes: In group 1, five infarcts were due to cardiogenic embolism and three to embolism from the aorta. One patient had a postoperative pontine lacunar infarct and one developed an infarct in the territory of a known stenotic basilar artery. In group 2, one patient had vertebral artery injury from instrumentation, one had medical complications with severe hemorrhage and hypotension, and 10 most likely had position-related vertebral artery thromboses. CONCLUSIONS: Patients with postoperative brainstem and cerebellar infarcts present with altered consciousness or vestibulocerebellar syndromes. The major cause of brain infarcts after cardiac surgery is embolism from the heart and aorta. The causes of infarction after general surgery are less clear, but neck positioning during or after surgery may play an important role by promoting thrombi in compressed arteries that later embolize intracranially when neck motion becomes free.

Adolescent↗

The detection of prostate specific antigen, MHS-5, and other markers in invasive prostate cancer and seminal vesicle.

Prostate specific antigen (PSA) is the most useful serum marker for following the disease status of prostate cancer patients after therapy. While PSA is felt to be an organ specific marker, lack of PSA expression in the seminal vesicles has not been adequately established. MHS-5 is a monoclonal antibody which recognizes an epitope on seminal vesicle specific antigen. Our objectives were to define PSA expression by the seminal vesicles, to determine whether MHS-5 could serve as an adjunct in the diagnosis of seminal vesicles invasion by carcinoma of the prostate, and to determine whether carcinoma, having invaded seminal vesicles would retain its expression of PSA and other prostate markers. Using an immunoperoxidase procedure, we studied thirteen seminal vesicles without histologic evidence of prostate cancer invasion and five seminal vesicles with locally invasive cancer. No seminal vesicles expressed PSA, whereas prostate cancer invading the seminal vesicles expressed PSA in all cases. MHS-5 expression was more variable. Only two of five cases of locally invasive tumor demonstrated seminal vesicles expression for MHS-5. Our findings further support the specificity of PSA. While MHS-5 may be helpful in delineating seminal vesicles in some instances, it is not a consistently reliable marker.

Antibodies, Monoclonal↗

Generation and characterization of monoclonal antibodies to prostate secretory protein.

Monoclonal antibodies (MAbs) were produced against a highly purified preparation of prostate secretory protein (PSP) isolated from normal seminal plasma. Fifteen antibodies were selected for further evaluation based on their strong reactivity and specificity for PSP. All the MAbs had a specificity for prostate epithelial cells and none reacted to any of a variety of normal tissues as determined by immunoperoxidase staining. Six of the MAbs were selected for further immunohistochemical evaluation based on their ability to recognize different antigenic determinants. Using competitive binding immunoassays, a variety of overlapping specificities were observed with at least 2 distinct epitopes identified. Although some staining variability was noted, the 6 antibodies, in general, gave the same pattern of tissue reactivity. Both the normal prostate and the benign prostate hyperplastic ductal epithelial cells stained intensely, with 78 to 100% and 50-100% of the cells staining, respectively. The number and often the staining intensity of the tumor cells decreased as the tumor became more undifferentiated. Approximately 40 to 100% and 15 to 70% of the tumor cells stained in the moderately-differentiated and well-differentiated carcinoma tissues, respectively, whereas either no staining was observed or less than 20% of the tumor cells stained in the poorly-differentiated and undifferentiated tumors. Most of the metastatic prostate tumors showed either no staining or scattered staining in a few cells (i.e., less than 20%).

Adenocarcinoma↗

Use of Y chromosome specific probes to detect low level sex chromosome mosaicism.

An individual found to be a true hermaphrodite at laparotomy, is presented. Cytogenetic studies which initially disclosed a 46,XX karyotype, conflicted with the anatomic presence of a testis. More extensive analysis of peripheral lymphocytes and skin fibroblasts revealed low level 46,XX/69,XXY mosaicism. DNA hybridization studies, using highly repeated Y chromosome specific probes, confirmed the rare presence of Y chromosome bearing cells. Such combined clinical and molecular studies can have an important impact on diagnosis and management of cases in which sex chromosome mosaicism is suspected.

Child, Preschool↗

Pleural effusion: the thorn sign. Not a rare finding.

Eleven percent of an unselected series of 157 patients with pleural effusion showed a thorn-like protrusion of fluid at the lateral end of the minor fissure at some time during their illnesses. None of a series of 146 normal x-ray films of young patients showed this "thorn sign." The thorn sign is a useful radiographic finding of right-sided pleural effusion.

Adolescent↗

IgE antibody production in guinea pigs treated with cyclophosphamide.

Guinea pig anaphylactic responses usually involve IgG1 antibodies. Although IgE antibody production has been accomplished, a reliable and sustained method for production has not been described. We have investigated a method of enhancing IgE antibody production in guinea pigs. The criteria for IgE production were homologous passive cutaneous anaphylaxis (PCA) antibody activity that passed an affinity column of rabbit anti-guinea pig IgG1, heat lability (56 degrees C for 3 hr), and a long sensitization period in skin (7 days). Hartley guinea pigs were primed and boosted monthly with 1 microgram Picryl-Ascaris plus 1 mg of alum i.p. Some Hartley guinea pigs also received cyclophosphamide (250 mg/kg) before the first boost. English short-hair guinea pigs (previously shown to be good IgE producers) were immunized similarly but received no cyclophosphamide. Hartley animals receiving no cyclophosphamide inconsistently made low titered IgE anti-hapten antibody (1:100). Fifteen of 15 Hartley animals that received cyclophosphamide had high titers (1:2000) of IgE anti-hapten antibody. English short-hair animals had moderate titers (1:400), and not all animals responded. Thus, cyclophosphamide converted IgE nonresponder Hartley guinea pigs to uniformly high responders. This method provides material to study the biologic properties of IgE in this species, and also provides a model to study the apparent suppression of IgE responses in Hartley guinea pigs.

Animals↗