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J D Wilson

Publications and source records attributed to J D Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1999

17Beta-hydroxysteroid dehydrogenase 3 deficiency in women.

In genetic males, mutation of the 17beta-hydroxysteroid dehydrogenase 3 (17HSD3)gene that is normally expressed in the testes impairs testosterone formation and causes development of male pseudohermaphroditism. We have ascertained seven women who are sisters of men with 17HSD3 deficiency and who are either homozygotes or compound heterozygotes for the same mutations as their affected brothers. Our findings confirm the concept that women with such mutations are asymptomatic.

17-Hydroxysteroid Dehydrogenases↗
PubMed1999

Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD.

STUDY OBJECTIVE: To conduct a post hoc pharmacoeconomic evaluation of two double-blind, randomized, prospective, parallel group studies comparing the long-term efficacy and safety of ipratropium combined with albuterol in a single inhalational canister against either bronchodilator agent alone in patients with COPD. PATIENTS: One thousand sixty-seven patients with COPD. METHODS: The dose of each bronchodilator was two puffs four times a day (42 microg of ipratropium bromide, 240 microg of albuterol sulfate). Pulmonary function testing was performed on days 1, 29, 57, and 85 of treatment. Outcomes, health-care resource consumption, and costs were compared for the three treatment groups over the 85-day study period. A total of 1,067 patients were randomized in the two studies (albuterol alone, n = 347; ipratropium alone, n = 362; albuterol plus ipratropium, n = 358). RESULTS: Improvement in FEV1 and area under the FEV1 response-time curve from time 0 to 4 h (FEV1AUC0-4) was significantly greater for the combination of albuterol plus ipratropium than either agent alone on all test days. Compared with albuterol, patients receiving ipratropium and ipratropium plus albuterol experienced significantly fewer COPD exacerbations and patient-days of exacerbation. In addition, the increased frequency of exacerbations observed in the albuterol group was associated with a significant increase in the number of patient hospital days and antibiotic and corticosteroid use. As a result, the total cost of treatment over the study period was significantly less for ipratropium ($156 per patient) and ipratropium plus albuterol ($197 per patient) than for albuterol ($269 per patient). Increased cost-effectiveness, defined as total estimated treatment cost per mean change in FEV1AUC0-4, was observed in both treatment arms containing ipratropium. CONCLUSIONS: The inclusion of ipratropium in a pharmacologic treatment regimen is associated with a lower rate of exacerbations in COPD. The result is lower total treatment costs and improved cost-effectiveness.

Adult↗
PubMed1998

Oligoclonal expansions of CD8(+) T cells in chronic HIV infection are antigen specific.

Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8(+) T cells. These 'expansions', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8(+) T cells. However, due to the difficulties in studying antigen-specific T cells in vivo, it has been hard to prove that oligoclonal BV expansions are actually HIV specific. The use of tetrameric major histocompatibility complex-peptide complexes has recently enabled direct visualization of antigen-specific T cells ex vivo but has not provided information on their clonal composition. We have now made use of these tetrameric complexes in conjunction with anti-BV chain-specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8(+) T cells are HIV specific in vivo.

CD8-Positive T-Lymphocytes↗
PubMed1998

Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo.

Primary infection with virus can stimulate a vigorous cytotoxic T cell response. The magnitude of the antigen-specific component versus the bystander component of a primary T cell response remains controversial. In this study, we have used tetrameric major histocompatibility complex-peptide complexes to directly visualize antigen-specific cluster of differentration (CD)8+ T cells during the primary immune response to Epstein-Barr virus (EBV) infection in humans. We show that massive expansion of activated, antigen-specific T cells occurs during the primary response to this virus. In one individual, T cells specific for a single EBV epitope comprised 44% of the total CD8+ T cells within peripheral blood. The majority of the antigen-specific cells had an activated/memory phenotype, with expression of human histocompatibility leukocyte antigen (HLA) DR, CD38, and CD45RO, downregulation of CD62 leukocyte (CD62L), and low levels of expression of CD45RA. After recovery from AIM, the frequency of antigen-specific T cells fell in most donors studied, although populations of antigen-specific cells continued to be easily detectable for at least 3 yr.

Antigens, CD↗
PubMed1998

Databases and software for the analysis of mutations in the human p53 gene, human hprt gene and both the lacI and lacZ gene in transgenic rodents.

We have created databases and software applications for the analysis of DNA mutations at the human p53 gene, the human hprt gene and both the rodent transgenic lacI and lacZ loci. The databases themselves are stand-alone dBASE files and the software for analysis of the databases runs on IBM-compatible computers with Microsoft Windows. Each database has a separate software analysis program. The software created for these databases permit the filtering, ordering, report generation and display of information in the database. In addition, a significant number of routines have been developed for the analysis of single base substitutions. One method of obtaining the databases and software is via the World Wide Web. Open the following home page with a Web Browser: http://sunsite.unc.edu/dnam/mainpage. html . Alternatively, the databases and programs are available via public FTP from: anonymous@sunsite.unc.edu. There is no password required to enter the system. The databases and software are found beneath the subdirectory: pub/academic/biology/dna-mutations. Two other programs are available at the site, a program for comparison of mutational spectra and a program for entry of mutational data into a relational database.

Animals↗
PubMed1998

Evidence for the persistence of monoclonal expansions of CD8+ T cells following primary simian immunodeficiency virus infection.

A longitudinal study of the CD8+ TCR variable (Vbeta) chain repertoire was performed in rhesus macaques experimentally infected with simian immunodeficiency virus (SIV) using both TCR Vbeta chain-specific monoclonal antibodies and TCR beta chain CDR3 length analysis. Expansions of subpopulations of CD8+ T cells were detected during the acute phase of SIV infection. In all monkeys studied, monoclonal expansions persisted for at least 18 months and increasingly dominated the repertoire of CD8+ T cells expressing the relevant Vbeta chain. This study shows that persistent CD8+ T cell expansions develop in response to a virus infection. This is important not only for our understanding of the T cell response to viruses but also for understanding the factors that determine the normal CD8+ TCR repertoire.

Animals↗
PubMed1998

Role of anti-donor antibody in the rejection of pig proislet xenografts in mice.

CBA/H mice produced serum anti-pig IgG1, IgG2a, and IgG2b following xenotransplantation of pig proislets beneath the kidney capsule; anti-pig IgM was present as pre-existing antibody in the serum of normal CBA/H mice and was also produced in response to pig proislet xenografts. Serum anti-pig IgG3 was not detected post-xenotransplantation. Rejection of pig proislet xenografts and the production of anti-pig IgG1, IgG2a, and IgG2b isotypes were CD4 T cell-dependent. The capacity for adoptively transferred hyperimmune CBA/H mouse anti-pig PBL serum to induce the rejection of intact pig proislet xenografts in CD4 T cell-depleted mice was dose dependent and correlated with markedly elevated levels of serum anti-pig IgG3. Levels of anti-pig IgG1, IgG2a, IgG2b, and IgM comparable to control mice acutely rejecting pig proislet xenografts and achieved following adoptive transfer of hyperimmune serum did not correlate with induced xenograft rejection. These findings suggest that anti-pig Ig isotypes produced during the conventional process of acute proislet xenograft rejection do not play a major role in mediating graft damage. The acute rejection of pig proislet xenografts in the absence of serum anti-pig Ig in microMT-/- hosts confirmed that anti-pig antibody is not essential for proislet xenograft destruction.

Adoptive Transfer↗
PubMed1998

Invasive infection with Fusarium chlamydosporum in a patient with aplastic anemia.

We report the first case of invasive disease caused by Fusarium chlamydosporum. The patient had aplastic anemia with prolonged neutropenia and was treated with immunosuppressive therapy. While she was receiving empirical amphotericin B, a dark crusted lesion developed on her nasal turbinate. Histologic analysis revealed invasive hyaline hyphae and some darkly pigmented structures that resembled conidia of dematiaceous molds. Only after the mold was grown in culture were characteristic colonial morphology, phialides, conidia, and chlamydospores evident, thus permitting the identification of F. chlamydosporum. This case illustrates the ever-increasing spectrum of pathogenic Fusarium spp. in immunocompromised patients and emphasizes the potential pitfalls in histologic diagnosis, which may have important treatment implications.

Adult↗
PubMed1998

Inactivation of the luteinizing hormone/chorionic gonadotropin receptor by an insertional mutation in Leydig cell hypoplasia.

We previously identified a nonsense mutation (Cys545Stop) in the paternal human LH/CG receptor (hLHR) allele in a family with two 46,XY children afflicted with Leydig cell hypoplasia. This mutation abolished the signal transduction capability of the affected hLHR. We have now examined all coding exons and the transcript of both alleles of the hLHR gene of the affected children. A 33-bp in-frame insertion was found in the maternal hLHR allele. This insertion occurred between nucleotide 54 and 55 and might be the result of a partial gene duplication. Genomic DNA-PCR showed that this defective maternal hLHR allele was inherited by the two affected children. However, examination of the inheritance of the 935-A/G polymorphism of the hLHR by genomic- and RT-PCR indicated that the maternal hLHR allele was not expressed in cultured fibroblasts of the patients. The effect of the in-frame insertion on the biological activity of the hLHR was examined by expressing the mutated hLHR construct, generated by site-directed mutagenesis, in HEK 293 cells. The expression of the mRNA for the mutant hLHR in HEK 293 cells was not affected. Response of cells expressing the mutated hLHR to hCG stimulation was impaired as demonstrated by reduced intracellular cAMP biosynthesis. This change in signal transduction was the result of a profound reduction in hormone binding at the cell surface due to altered expression and processing of the mutated receptor. We conclude that Leydig cell hypoplasia in this family is the result of compound heterozygous loss-of-function mutations of the hLHR gene.

Alleles↗
PubMed1997

Eosinophils are not required for the rejection of neovascularized fetal pig proislet xenografts in mice.

The rejection of neovascularized pig proislet (islet precursor) xenografts in mice is a CD4 T cell-dependent process involving invasion of the graft site mainly by host CD4 T cells and eosinophils. We previously identified CD4 T cell-dependent enhancement of intragraft IL-3, IL-4, and IL-5 mRNA expression during acute xeno-rejection in CBA/H recipient mice. In the present study we investigated the role of each cytokine and the involvement of eosinophils in the rejection of pig proislet xenografts using cytokine gene knockout mice (IL-4 -/- and IL-5 -/-) and the treatment of transplant recipients with anti-IL-3 mAb. In IL-4 -/- mice, IL-5 -/- recipient animals, and anti-IL-3 mAb-treated CBA/H mice, eosinophil accumulation at the transplant site was inhibited or ablated, but the kinetics of xenograft rejection was unaltered. Prolonged xenograft survival was only achieved in anti-CD4 mAb-treated mice and consistently correlated with the absence of intragraft IL-3, IL-4, and IL-5 mRNA enhancement. Together these findings indicate that neither IL-3, nor IL-4, nor IL-5 individually plays an obligatory role in the rejection process. The cytokine mRNA profile correlating with the lack of eosinophil recruitment was variable; the data suggest that IL-4 regulates eosinophil involvement in the xeno-rejection reaction indirectly via effects on IL-5 and IL-3 transcript expression. There is also suggestive evidence that IL-5 may influence IL-3 and IL-4 mRNA expression via feedback inhibition. Eosinophils, therefore, do not play an essential role in the rejection of neovascularized pig proislet xenografts in mice.

Animals↗
PubMed1997

The Ames miniscreen assay: volatility of sodium azide can cause an increase in the reversion frequencies of adjacent, untreated wells.

Sodium azide, when added to wells adjacent to untreated wells, caused an increase in the reversion rate of Salmonella typhimurium TA100 in a 12-well plate format. Increases in the reversion frequency in adjacent, untreated wells were observed when a single well on the plate was treated with as little as 1 microg of sodium azide. This effect is probably caused by the hydrolysis of sodium azide to form hydrazoic acid. Hydrazoic acid has a boiling point of 37 degrees C and, thus, would become a diffusible gas during the incubation of the plates. Our findings suggest that a diffusible gas is present and that this gas has the ability to contaminate nearby wells when using the multiwell version of the Ames assay. Furthermore, it may be prudent to isolate all positive controls and negative controls on separate plates with no test material since a volatile test material could produce spurious results in the Ames miniscreen.

Azides↗
PubMed1997

Time quantified detection of fetal movements using a new fetal movement algorithm.

Primarily, the objective is to develop an automated ultrasound fetal movement detection system that will better characterize fetal movements. Secondarily, the objective is to develop an improved method of quantifying the performance of fetal movement detectors. We recorded 20-minute segments of fetal movement on 101 patients using a UAMS-developed fetal movement detection algorithm (Russell algorithm) and compared this to a Hewlett-Packard (HP) M-1350-A. Movements were recorded on a second-per-second basis by an expert examiner reviewing videotaped real-time ultrasound images. Videotape (86,592 seconds) was scored and compared with the electronic movement-detection systems. The Russell algorithm detected 95.53% of the discrete movements greater than 5 seconds, while the HP system (M-1350-A) detected only 86.08% of the discrete movements (p = 0.012). Both devices were less efficient at detecting the short discrete movements, obtaining sensitivities of 57.39 and 35.22, respectively. Neither system fully identifies fetal movement based on the second-per-second system. Improved methods of quantifying performance indicated that the Russell algorithm performed better than the HP on these patients.

Adolescent↗