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A Moss

Publications and source records attributed to A Moss.

At least 55 records · Page 3Linked to original sources
PubMed1994

Evidence of genetic heterogeneity in Romano-Ward long QT syndrome. Analysis of 23 families.

BACKGROUND: The Romano-Ward long-QT Syndrome (LQTS) is an autosomal dominant inherited trait characterized by prolonged QT interval on ECG, life-threatening arrhythmias, syncope, and sudden death in affected individuals. A gene responsible for this disorder has been shown to be linked to the Harvey ras-1 locus (H-ras-1) DNA marker on the short arm of chromosome 11 (11p) in 7 families. The purpose of this study was to determine, by analyzing 23 families with LQTS for linkage to chromosome 11p, whether evidence exists for more than one gene causing LQTS (ie, locus heterogeneity). METHODS AND RESULTS: Twenty-three families (262 family members) were clinically evaluated using medical histories, ECGs, and Holter recordings. Each corrected QT interval (QTc) were determined using Bazett's formula. Blood for DNA extraction and cell line immortalization was obtained after informed consent. Southern blotting and polymerase chain reaction were performed, and linkage analysis carried out using the LINKAGE computer program (v 5.03). Genetic heterogeneity was determined using the HOMOG 2 (v 2.51) computer program. Twenty-three families were studied for evidence of linkage to chromosome 11p using the H-ras-1 locus probe pTBB-2 and multiple flanking markers, including tyrosine hydroxylase (TH). Two-point linkage analysis using pTBB-2 and TH markers was consistent with linkage in 15 of 23 families, with the maximum single-family LOD score of +3.038 occurring at theta = 0. However, 8 of 23 families had negative LOD scores, with the values in 4 families being less than -2 at theta = 0, consistent with exclusion of linkage. Analysis with the HOMOG program was consistent with genetic heterogeneity (P < .0001). Multipoint linkage data using pTBB-2 and TH were also examined for evidence of heterogeneity. HOMOG analysis of multipoint LOD scores from 100 cM surrounding the H-ras-1 locus also supported heterogeneity (P < .001). CONCLUSIONS: In the 23 families with LQTS analyzed for linkage to the H-ras-1 locus on chromosome 11p15.5, 15 of 23 families had LOD scores consistent with linkage. The remaining 8 of 23 families had negative LOD scores, 4 of which were definitively excluded from linkage. Thus, genetic heterogeneity is definitively (P < .001) demonstrated for this disorder.

Base Sequence↗
PubMed1994

Risk factors for anal human papillomavirus infection and anal cytologic abnormalities in HIV-positive and HIV-negative homosexual men.

Men with advanced human immunodeficiency virus (HIV) disease have a high prevalence of anal human papillomavirus (HPV) infection and potentially precancerous anal disease. To characterize prevalence of and risk factors for anal HPV infection and anal cytologic abnormalities, 37 HIV-positive and 28 HIV-negative participants in the San Francisco General Hospital Cohort Study were studied. A questionnaire was administered, followed by an anal examination consisting of two consecutive anal swabs for cytology and HPV DNA hybridization, and anoscopy with biopsy of visible lesions. Ten of 28 (36%) HIV-negative men and 19 of 37 (51%) HIV-positive men had anal HPV infection (p = 0.32). Risk factors for anal HPV infection included HIV positivity with a CD4 count < 200/mm3 (p = 0.03) and a history of smoking (p = 0.03). Abnormal anal cytology was found in 2 of 26 (8%) HIV-negative men and 10 of 36 (28%) HIV-positive men with cytology adequate for interpretation (p = 0.09). Risk factors for abnormal anal cytology included HIV positivity with a CD4 count < 200/mm3 (p = 0.006) and current smoking (p = 0.03). We conclude that the risk of development of anal disease and HPV infection was highest among HIV-positive men with a CD4 count of < 200/mm3, and that smoking may play a role in the pathogenesis of anal disease.

Adult↗
PubMed1993

Human T cell leukemia virus (HTLV-I/II) serodiagnostic testing: disparate results among a cohort of intravenous drug users.

Three hundred and forty-six sera collected over a 2-year period from 154 San Francisco IV drug users were subjected to HTLV-I/II RIPA, Western blot (WB), Du Pont ELISA, and p24 radioimmunoassay (RIA). Tests were performed at separate sites and code not broken until study end. RIPA-positive and -negative controls consisted of Japanese adult T cell leukemia patients, healthy blood donors, and non-IV drug-using HIV-positive men. RIPA identified HTLV-I/II-positive sera not identified by the other tests. Positive RIPAs were noted in 43% of negative ELISAs (n = 279), 34% of negative WBs (n = 243), and 40% of negative RIAs (n = 270). Seventy-two sera were negative by all 3 assays, but were RIPA positive. All sera positive by RIA (n = 76) and WB (n = 67), and 66 of 67 by ELISA, were positive by RIPA. Thirty-five of 36 indeterminate WBs were RIPA positive. Seven samples indeterminate by RIPA were negative by WB and RIA; one of seven was positive by ELISA. In all instances, samples negative by RIPA (n = 154) were ELISA, p24 RIA, and WB negative or indeterminate. We conclude that when studying HTLV-I/II-endemic cohorts, screening ELISA or RIA followed by confirmatory WB or RIPA only of seropositive samples may result in a substantial number of undetected cases. Additional studies focusing on performance characteristics of serodiagnostic tests are needed to ensure accurate inferences are made in assessing HTLV-I/II prevalence rates among high-risk groups. The RIPA may be a uniquely sensitive assay to detect HTLV-I/II gene-encoded products.

Adult↗
PubMed1993

Phosphotyrosine-containing proteins in the CNS of obese Zucker rats are decreased in the absence of changes in the insulin receptor.

The location and quantity of the insulin receptor and its associated tyrosine kinase activity have been examined in the forebrains of lean (Fa/?) and obese (fa/fa) Zucker rats using immunocytochemistry (ICC) and biochemical procedures. These studies were performed in conjunction with ICC and Western blot analysis of phosphotyrosine-containing proteins (PY-proteins). The results from ICC show a similar distribution and content for the insulin receptor among forebrain regions of lean and fatty Zucker rats. Biochemical analysis of the receptor was conducted on the hippocampus. Insulin binding studies using lectin-purified receptor extracts demonstrated similar receptor number and comparable hormone binding affinity for lean and obese animals. Autophosphorylation studies with the receptor extracts from the two groups did not find any differences in the tyrosine kinase activity of insulin receptors. In contrast to the normal findings with the insulin receptor, an abnormality in the obese animals was evident in the content of PY-proteins detected by ICC in the hippocampus, piriform cortex and olfactory bulb. Neurons in these brain regions showed a reduction in staining by an antibody against PY-proteins. Furthermore, Western blots of hippocampal extracts from obese rats demonstrated a reduction in phosphotyrosine content of two proteins of Mr 180 and 130 kD. These findings point to a previously unrecognized alteration in the CNS of the obese, insulin-resistant Zucker rat.

Amino Acid Sequence↗
PubMed1993

Molecular epidemiology and the new tuberculosis.

DNA fingerprinting techniques now exist which identify specific strains of Mycobacterium tuberculosis. These techniques may be integrated with conventional epidemiologic approaches to better understand tuberculosis in its modern form. This paper reviews the lessons learned from this approach about the pathogenesis and epidemiology of tuberculosis. In addition, it speculates about the potential future applications of molecular epidemiology, including its use as an adjunct to conventional public health measures.

DNA Fingerprinting↗
PubMed1993

Rapamycin: immunosuppression, hyporesponsiveness, and side effects in a porcine renal allograft model.

Rapamycin prolongs allograft survival and induces donor-specific tolerance in some small animal transplant models. Large animal studies, however, are limited. We studied rapamycin in a porcine renal allograft model. Donor-recipient combinations were chosen based on high response in pretransplant MLCs. Allografts were anastomosed to the aorta and vena cava and the native kidneys removed. There were 5 treatment groups: (a) no immunosuppression; (b) triple therapy (CsA, 1 mg/kg/day; AZA, 2-3 mg/kg/day; and PRED, 3-4 mg/kg/day); (c) rapamycin (0.75 mg/kg/day i.m.) in carboxymethylcellulose (CMC); (d) rapamycin (0.25 mg/kg/day i.m. in CMC); and (e) a vehicle (CMC) control. Serum creatinine levels were determined every other day. Most allografts were biopsied once a week. Immunosuppression was stopped after 30 days. Mean graft survival in nonimmunosuppressed recipients was 6.8 +/- 3.6 days. Mean graft survival in triple therapy recipients (n = 10) was 45.7 +/- 36 days vs. 59.6 +/- 11.4 days in rapamycin (0.25 mg/kg/day) recipients (n = 7) (P = 0.51). Both triple therapy and rapamycin improved renal allograft survival versus nonimmunosuppressed controls (P = 0.0025 and 0.001, respectively). Serum creatinine levels were significantly lower (P < 0.05) in rapamycin versus triple therapy recipients. We conclude that rapamycin is a potent immunosuppressant in a porcine renal allograft model and may avoid the elevated serum creatinine levels associated with CsA.

Animals↗
PubMed1993

Population-based estimates of antiretroviral therapy and anti-Pneumocystis prophylaxis in San Francisco: 1991.

Using data from the San Francisco Men's Health Study and the San Francisco General Hospital Cohort, we derived partially population-based estimates of human immunodeficiency virus (HIV) antiretroviral therapy and Pneumocystis carinii prophylaxis use in HIV-infected men in 1991. Zidovudine, didanosine, and dideoxycytidine were the antiretroviral therapies and aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone were the Pneumocystis prophylaxis evaluated. Among 81 men (29 of whom had AIDS) with < or = 200 CD4 cells, 76 (94%) had ever used and 56 (69%) were currently using an antiretroviral drug; 73 (90%) had ever used and 61 (75%) were currently using Pneumocystis prophylaxis. Among 127 men with 201-499 CD4 cells, 95 (75%) had ever used and 81 (64%) were currently using antiretroviral therapy; 49 (39%) had ever used and 36 (28%) were currently using Pneumocystis prophylaxis. Among 122 men with > or = 500 CD4 cells, 29 (24%) were currently receiving antiretroviral therapy. Forty-three men had discontinued antiretroviral therapy, 29 (67%) because of side effects. Thirty-seven men with < or = 500 CD4 cells had never used antiretroviral drugs: 48% because of feeling well and 28% because of possible side effects. Compared with 1987-1989, there were substantial increases in both antiretroviral therapy and anti-Pneumocystis prophylaxis use.

AIDS-Related Opportunistic Infections↗
PubMed1992

Progression to AIDS in HIV-infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis.

OBJECTIVE: This study was designed to assess the significance of HIV-related oral lesions in predicting the rate of progression to AIDS. DESIGN: Cohorts were investigated prospectively, and oral examinations were performed by clinicians trained in the diagnosis of oral lesions. SETTING: We studied three existing cohorts of homosexual and bisexual men in San Francisco, California, USA. PARTICIPANTS: Of the HIV-infected men who received standardized oral examinations (n = 791), 603 were eligible for analysis of baseline examinations and 448 for analysis of follow-up examinations. MAIN OUTCOME MEASURES: We determined time from presence of oral lesion at baseline or follow-up examination, or from participant self-reported history of the lesion, to diagnosis of AIDS. RESULTS: Using proportional hazard regression and stratifying by CD4 lymphocyte count at the time of baseline oral examination, we found that the rate of development of AIDS was increased among men with hairy leukoplakia [relative hazard, 1.8; 95% confidence interval (CI), 1.2-2.7], oral candidiasis (relative hazard, 7.3; 95% CI, 3.1-17.3), and both lesions (relative hazard, 3.1; 95% CI, 1.6-6.1) compared with men with normal findings. On follow-up examination, stratifying for CD4 count, the rate of progression to AIDS was similar for those with hairy leukoplakia compared with those with oral candidiasis. The progression rate from oral candidiasis to AIDS was faster from presence on baseline examination than from presence on follow-up examination or from self-reported history of the lesion. CONCLUSION: The presence of oral candidiasis and/or hairy leukoplakia on baseline examination confers independent prognostic information and should be incorporated into HIV-staging schemes.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Mizoribine pharmacokinetics and pharmacodynamics in a canine renal allograft model of local immunosuppression.

We utilized a canine renal transplant model to estimate the first-pass extraction of mizoribine (MZB) during renal artery infusion and to compare the efficacy and toxicity of continuous intraarterial (i.a.) versus intravenous (i.v.) MZB delivery, with and without a background of oral cyclosporine. Five autotransplanted mongrel dogs with programmable, implantable pump/catheter systems were given MZB by both i.v. bolus (5 mg/kg) and i.a. infusion (5.0 mg/kg/day). Mean +/- SD elimination half-life was 3.02 +/- 0.81 hr, and the transplanted kidney removed as much as 47-59% (mean 56%) of locally infused MZB. With increasing local and systemic MZB delivery in a single autografted dog undergoing both i.a. and i.v. pump/catheter placement, renal extraction decreased from at least 47% (5.0 mg/kg/day) to 33% (7.5 mg/kg/day), finally to 18% (10.0 mg/kg/day). A dose of 3.0 mg/kg/day MZB did not significantly prolong survival of renal allograft recipients over that of untreated controls (median survival time [MST] = 8 days) when administered either locally (MST = 9 days) or systemically (MST = 12 days). All dogs receiving 4.0 mg/kg/day MZB i.a. died from rejection, and a survival advantage was still not realized (MST = 7 days). In contrast, 4.0 mg/kg/day i.v. prolonged survival over controls (MST = 14 days; P = 0.03) but not when directly compared with the i.a. group (P = 0.30), and produced death from severe debility in five of seven animals with significantly higher mean systemic MZB levels (P = 0.02). Four of six dogs receiving 5.0 mg/kg/day MZB i.a. (MST = 14 days) and two of four dogs receiving 5.0 mg/kg/day i.v. (MST = 14 days) died from severe debility, though survival in both groups was prolonged over control values (P = 0.01 and P = 0.05, respectively). Coadministration of a subtherapeutic dose of oral CsA (5 mg/kg/day) significantly prolonged the overall survival of dogs receiving MZB 4.0 mg/kg/day i.a. (MST = 23; P = 0.01) but not i.v. (MST = 11; P = 1.00), so that a significant difference in overall survival between the combined MZB i.a. + CSA and MZB i.v. + CSA groups was now realized in favor of the former (P = 0.04). We conclude that at local doses required to achieve immunosuppression, the transplanted kidney was not able to extract enough MZB to prevent death from systemic toxicity, presumably as a result of saturation of renal elimination mechanisms, so that an overall survival benefit was not realized.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Pediatric renal transplants--results with sequential immunosuppression.

Cyclosporine has improved the results of renal transplantation. In 1984, we began using it as part of a sequential immunosuppression protocol (MALG, AZA, P, and delayed administration of CsA) in our pediatric renal transplant recipients. We studied the outcome of the 131 pediatric renal transplants (less than or equal to 18 years of age at transplant) performed at our institution between June 1984 and March 1991. We compared these results with the 144 similar transplants performed since January 1980 that did not involve CsA immunosuppression. In the sequential immunosuppression group, there were 97 primary (74%) (26 [27%] cadaver, 71 [73%] living donor [LD]) and 34 (26%) retransplant (23 [68%] CAD, 11 [32%]) recipients. Age at transplant (mean +/- SD) was 7.4 +/- 5.5. Overall, 1-year actuarial graft survival was 93%; 1-year patient survival was 100%. The mean number of hospital readmissions was 3.0 +/- 3.5; 26 (20%) were readmission-free. The mean number of rejection episodes was .87 +/- 1.3 per patient; 73 (56%) were rejection-free. Importantly, LD (vs. CAD) recipients had fewer rejection episodes (P = 0.06). In the first post-transplant year, the serum creatinine level was significantly lower in primary (vs. retransplant) recipients and in LD (vs. CAD) recipients (P less than 0.05). In the 144 patients not receiving CsA, there were 129 (90%) primary (27 CAD, 102 LD) and 15 (10%) retransplant (7 CAD, 8 LD) recipients. Age at transplant was 6.9 +/- 5.3 years. The 1-year actuarial graft survival rate was 82%; the 1-year patient survival rate was 94%. The mean number of hospital readmissions was 3.3 +/- 2.3; 5 (8%) were readmission-free. The mean number of rejection episodes was 1.2 +/- 1.5; 27 (45%) were rejection-free. There was no difference in the serum creatinine level based on donor source or transplant number. Sequential immunosuppression has significantly improved patient (P = 0.003) and graft survival (P = 0.004) rates. Comparing sequential vs. non-CsA immunosuppression, there was no difference in the number of readmissions (P = 0.47), number of rejection episodes (P = 0.17), or serum creatinine level. The number of rejection-free patients was significantly lower in LD (vs. CAD) recipients (P less than 0.05). There was no evidence of progressive deterioration in renal function in the sequential (vs. non-CsA) recipients.

Adolescent↗
PubMed1992

Renal transplant function after ten years of cyclosporine.

Although the nephrotoxic side effects of cyclosporine are well known, the impact of long-term CsA on renal transplant function is uncertain. We studied 5-10-year renal function in 347 CsA-treated patients, and in 64 randomly selected non-CsA-treated patients who had a minimum of 55 months of graft function. Non-CsA patients had a lower creatinine (Cr) level at one year than CsA patients (P = .001), with no change in renal function over time (P = .6). In CsA-treated patients there was also no suggestion of progressive renal damage, as evidenced by no change in Cr or 1/Cr. Simple linear regression models of 1/Cr vs. time for the first 10 years posttransplant were fit to the data for each patient. Analysis of the Y-intercept estimates from these regressions showed that age (P = .001), sex (P = .001), cyclosporine toxicity (P = .024), and initial cyclosporine dosage (P = .016) significantly affected the one-year serum Cr. Variables not affecting one-year Cr included donor source, early rejection episodes, late rejection episodes, ATN, diabetes, transplant number, HLA ABDR mismatch (for cadaver transplants), maximum PRA, and PRA at transplant. Analysis of the slope estimates from the regressions revealed that only age (P = .001) and late rejection episodes (P = .001) significantly affected the rate of change in 1/Cr over time. We conclude that, in long-term renal transplant patients, there is no evidence of progressive deterioration in renal function due to CsA nephrotoxicity.

Creatinine↗