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Biomedical subjects

H Joseph

Publications and source records attributed to H Joseph.

At least 19 recordsLinked to original sources
PubMed2004

Plasma erythropoietin levels in the oldest old.

UNLABELLED: Erythropoietin (EPO) regulates erythrocytes production and is synthesized mainly by the kidney. Its production is reduced during chronic renal failure but is not altered by the senescence process in spite of the morphological changes that occur in the kidney. However, there is no information regarding what happens to erythropoietin synthesis during advanced ageing. Thus, we carried out an investigation to determine whether there was any significant difference in plasma erythropoietin between adults, old and very old people. MATERIAL AND METHODS: We studied 74 healthy volunteers: 22 adults, 30 old, and 22 very old. None of them were smokers or were suffering from any disease that may intefere with hemoglobin (Hb) levels or with EPO production. Hematocrit, Hb, plasma creatinine and plasma erythropoietin were measured, and creatinine clearance was calculated from serum creatinine using two different formulae. Statistical analysis was performed using ANOVA and Bonferroni tests. RESULTS AND CONCLUSION: Among the three groups we found a significant difference in creatinine clearance (p < 0.001), but not in plasma erythropoietin levels; we conclude that normal senescence does not alter plasma erythropoietin levels, even during advanced ageing.

Adolescent↗
PubMed2001

Hepatitis C and substance use in a sample of homeless people in New York City.

This study examined the prevalence of hepatitis C virus (HCV) antibodies and its association with substance use and sexual behavior among a sample of 139 persons visiting a mobile medical clinic in Manhattan. Ninety percent were unstably housed or were living on the street. The prevalence of HCV antibodies was 32%. Prevalence was also high for hepatitis B core antibodies (47%), HIV antibodies (15%), and syphilis exposure (14%); 76% tested positive for cocaine. Among subjects who reported ever injecting (20%), 86% were HCV positive; 19% of non-injectors were HCV positive. In separate multivariate logistic regression models (with injection controlled), HCV was predicted by quantitative hair assays for cocaine and self-reported duration of crack-cocaine use. Alcohol dependence and sexual behavior did not predict HCV. Hepatitis C is a significant public health problem among the urban homeless population, with injection drug use and, to a lesser extent, cocaine use implicated as risk factors.

Adult↗
PubMed2001

Integrating the methadone patient in the traditional addiction inpatient rehabilitation program--problems and solutions.

Physicians have reported alcoholism and opioid addiction as co-morbid conditions since the 19th century. From the inception of methadone maintenance treatment, heroin addicts with serious alcohol conditions have enrolled in methadone maintenance programs. Programs that treat alcoholism, including the traditional addiction inpatient rehabilitation programs of the Addiction Treatment Centers (ATCs) operated by New York State, have based their treatment regimen on 12-step abstinence models. Methadone maintenance was considered antithetical to this philosophy. It was regarded as simply substituting one drug for another and not a legitimate treatment for opiate dependence. Therefore, methadone patients were often not accepted into alcohol treatment programs, since they were perceived as active addicts taking a mood-altering drug. Alcohol-related conditions among methadone patients are major causes of liver disease and death, and behavior problems associated with excessive drinking are major reasons for discharging patients. To address these issues and the lack of treatment facilities, the administration of the New York State Office of Alcoholism and Substance Abuse Services (OASAS), which licenses both methadone programs and the ATCs in New York State, realized that many of the methadone patients with alcohol problems are in need of the services provided at the ATCs. They instituted, therefore, a rigorous educational effort for the medical and counseling staffs of the ATCs, designed to integrate methadone treatment into the ATC treatment framework. Eighty percent of the 220 methadone patients who entered the ATCs in a demonstration project during the 1997/1998 state fiscal year have been compliant with the treatment regimen. These results have led to acceptance of methadone patients into the ATCs.

Alcoholism↗
PubMed2001

Selected in-treatment outcomes of long-term methadone maintenance treatment patients in New York State.

The New York State Office of Alcoholism and Substance Abuse Services (OASAS) licenses the largest system of methadone maintenance clinics nationwide. In 1996, a survey was undertaken to evaluate the functioning of patients continuously active in treatment for ten or more years. Information was obtained on a 10% random sample from the OASAS client data system and the records of the clinics. Data were collected concerning methadone dose, illicit drug and problematic alcohol use, employment, criminal activity, health, living situations, and the primary type of payment for treatment. A contrast group was constructed of discharged patients who had no more than 5 years of continuous treatment. The long-term active patients in the study sample showed superior outcomes on all variables, although some of the differences were small. However, the arrest rate for the discharged contrast group was 20 times as large as the arrest rate for the active study sample. These results are consistent with nationwide evaluations of methadone maintenance treatment. Factors that negatively impacted on the adjustments of the active patients were heavy use of crack/cocaine and disabilities. The long-term active patients in this sample belong to distinct subgroups with different levels of functioning, achievement, and ongoing health and social needs that must be investigated and addressed.

Alcoholism↗
PubMed2001

[Effect of rheumatoid arthritis associated HLA-DRbeta1 subtypes on protein kinase A signaling].

OBJECTIVE: To investigate the impact of rheumatoid arthritis (RA)-associated HLA-DRbeta(1) (*)0401, (*)0402, (*)0403 and (*)0404 subtypes on protein kinase A (PKA) signaling. METHODS: To detect the activities of adenylate cyclase (AC), cAMP and PKA in transfectants expressing rheumatoid arthritis-associated HLA-DRbeta(1) subtypes and their mutants. RESULTS: The levels of AC, cAMP and PKA of HLA-DRbeta(1) (*)0401 and (*)0404 transfectants were significant lower than that of HLA-DRbeta(1) (*)0402 and (*)0403 transfectants (P < 0.01). The mutant HLA-DRbeta(1) (*)0403 transfectants expressing DRRAE or QRRAA secreted lower levels of PKA, cAMP and AC (P < 0.01). CONCLUSION: RA-associated HLA-DRbeta(1) (*)0401 and (*)0404 expression suppressed intracellular PKA signaling pathway, and may mediate abnormal intracellular signaling in rheumatoid arthritis.

Adenylyl Cyclases↗
PubMed2000

Reduced antibody response to revaccination with meningococcal serogroup A polysaccharide vaccine in adults.

Widespread use of meningococcal A and C polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to these polysaccharides. Immunological hyporesponsiveness to C polysaccharide has been clearly documented in infants, children and adults but only limited data from Gambian children are available for A polysaccharide. We investigated whether a second dose of MACP, given 6 months after an initial dose affected the immunological response as measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay (ELISA), to serogroup A meningococci in young adults (university students, n=36). Serogroup A SBA responses 1 month following the second dose of MACP (geometric mean titre (GMT) 103.6, 95% CI 45.6-235.1) were approximately one third of the levels observed 1 month post first dose (GMT 281.9, 95% CI 134.9-581.4). The serogroup A-specific IgG levels post second dose (GMC 21.2, 95% CI 15.3-29.4) were also significantly lower at an average of three-quarters the level post first dose (GMC 28.7, 95% CI 20.8-39.7). This confirms that revaccination with MACP vaccine, 6 months following the initial dose, results in a reduced immunological response to A polysaccharide in adults. Repeated vaccination with MACP vaccine may be ineffective and development and use of meningococcal serogroup A conjugate vaccines should be encouraged.

Adolescent↗
PubMed2000

The association between cocaine use and HIV/STDs among soup kitchen attendees in New York City.

We examined the associations of cocaine use with HIV/sexually transmitted diseases (STDs) in a sample of 184 soup kitchen attendees using a mobile medical van in Manhattan (male = 66%; black or Hispanic = 81%; cocaine use, primarily crack = 75%; ever injected drugs = 22%). In addition to confirming the association between years of cocaine use and HIV antibodies in this sample (odds ratio [OR] = 2.11; p <.05) we examined the pattern of associations of cocaine use and non-HIV STDs under the hypothesis that the strength of an association depends on the efficiency of sexually transmitting a particular STD (high, moderate, and low for syphilis, hepatitis B and hepatitis C, respectively). As predicted, years of cocaine use was strongly associated with syphilis (OR = 2.07; p <.05), moderately associated with hepatitis B core antibodies (OR = 1.50; p <.05), and not significantly associated with hepatitis C antibodies (OR = 1.48; p >.05). A reverse pattern of associations between opiate use (injection drug use) and the three STDs points to the singular significance of cocaine use in the sexual transmission of STDs, and by inference, HIV. This conclusion is further bolstered by correlations of biologic (hair assays) and self-reported measurements of cocaine use (but not opiates) with self-reports of high risk sexual behavior among the women (number of partners and selling sex) and men (number of partners and buying sex). These data underscore the need for effective cocaine treatment and HIV interventions tailored to the large numbers of cocaine users in inner cities.

Adult↗
PubMed2000

Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2.

Tuberculosis is a major cause of death in much of the world. Current estimates are that one-third of the world's population is infected with Mycobacterium tuberculosis. Most infected persons control the infection but in many cases may not eliminate the organism. Reactivation of this clinically latent infection is responsible for a large proportion of active tuberculosis cases. A major risk factor for reactivation of latent tuberculosis is HIV infection, suggesting a role for the CD4(+) T cell subset in maintaining the latent persistent infection. In this study, we tested the requirement for CD4(+) T cells in preventing reactivation in a murine model of latent tuberculosis. Antibody-mediated depletion of CD4(+) T cells resulted in rapid reactivation of a persistent infection, with dramatically increased bacterial numbers in the organs, increased pathology in the lungs, and decreased survival. Although CD4(+) T cells are believed to be a major source of interferon (IFN)-gamma, expression of the gene for IFN-gamma in the lungs of CD4(+) T cell-depleted mice was similar to that in control mice. In addition, inducible nitric oxide synthase production and activity was unimpaired after CD4(+) T cell depletion, indicating that macrophage activation was present even during CD4(+) T cell deficiency. These data indicate that CD4(+) T cells are necessary to prevent reactivation but may have roles in addition to IFN-gamma production and macrophage activation in controlling a persistent tuberculous infection.

Animals↗
PubMed2000

Substance misuse and related infectious diseases in a soup kitchen population.

Representative samples of female (N = 119) and male (N = 100) guests were selected at two inner city soup kitchens. In the preceding month, 75% used cocaine/crack and 25% used heroin/opiates as determined by hair analysis. Relatively few guests (25%) were in substance dependency treatment. Infectious disease rates were: HIV (16%), hepatitis B exposure (21%), hepatitis B carrier (6%), syphilis exposure (15%). Years of injecting drug use and homelessness/marginal housing were associated with HIV infection and hepatitis B exposure. Soup kitchens should be prime locations for outreach to cocaine/crack and heroin users in need of treatment, medical care, and interventions to prevent infectious disease transmission.

Cocaine-Related Disorders↗
PubMed1999

Overexpression of a kinase-deficient transforming growth factor-beta type II receptor in mouse mammary stroma results in increased epithelial branching.

Members of the transforming growth factor-beta (TGF-beta) superfamily signal through heteromeric type I and type II serine/threonine kinase receptors. Transgenic mice that overexpress a dominant-negative mutation of the TGF-beta type II receptor (DNIIR) under the control of a metallothionein-derived promoter (MT-DNIIR) were used to determine the role of endogenous TGF-betas in the developing mammary gland. The expression of the dominant-negative receptor was induced with zinc and was primarily localized to the stroma underlying the ductal epithelium in the mammary glands of virgin transgenic mice from two separate mouse lines. In MT-DNIIR virgin females treated with zinc, there was an increase in lateral branching of the ductal epithelium. We tested the hypothesis that expression of the dominant-negative receptor may alter expression of genes that are expressed in the stroma and regulated by TGF-betas, potentially resulting in the increased lateral branching seen in the MT-DNIIR mammary glands. The expression of hepatocyte growth factor mRNA was increased in mammary glands from transgenic animals relative to the wild-type controls, suggesting that this factor may play a role in TGF-beta-mediated regulation of lateral branching. Loss of responsiveness to TGF-betas in the mammary stroma resulted in increased branching in mammary epithelium, suggesting that TGF-betas play an important role in the stromal-epithelial interactions required for branching morphogenesis.

Animals↗
PubMed1999

Reactivation of latent tuberculosis: variations on the Cornell murine model.

Mycobacterium tuberculosis causes active tuberculosis in only a small percentage of infected persons. In most cases, the infection is clinically latent, although immunosuppression can cause reactivation of a latent M. tuberculosis infection. Surprisingly little is known about the biology of the bacterium or the host during latency, and experimental studies on latent tuberculosis suffer from a lack of appropriate animal models. The Cornell model is a historical murine model of latent tuberculosis, in which mice infected with M. tuberculosis are treated with antibiotics (isoniazid and pyrazinamide), resulting in no detectable bacilli by organ culture. Reactivation of infection during this culture-negative state occurred spontaneously and following immunosuppression. In the present study, three variants of the Cornell model were evaluated for their utility in studies of latent and reactivated tuberculosis. The antibiotic regimen, inoculating dose, and antibiotic-free rest period prior to immunosuppression were varied. A variety of immunosuppressive agents, based on immunologic factors known to be important to control of acute infection, were used in attempts to reactivate the infection. Although reactivation of latent infection was observed in all three variants, these models were associated with characteristics that limit their experimental utility, including spontaneous reactivation, difficulties in inducing reactivation, and the generation of altered bacilli. The results from these studies demonstrate that the outcome of Cornell model-based studies depends critically upon the parameters used to establish the model.

Animals↗
PubMed1999

Treatment with farnesyl-protein transferase inhibitor induces regression of mammary tumors in transforming growth factor (TGF) alpha and TGF alpha/neu transgenic mice by inhibition of mitogenic activity and induction of apoptosis.

Mouse mammary tumor virus-transforming growth factor alpha (MMTV-TGF alpha) and MMTV-TGF alpha/neu transgenic mice develop mammary tumors after a long latency and therefore provide useful model systems for breast cancer with its recognized activation of receptor tyrosine kinase signaling. We used these mice to study the antitumor effect of L-744,832 (FTI), a potent and selective inhibitor of farnesyl-protein transferase, and hence of Ras function. A total of 55 mice were assigned randomly to treatment with FTI or vehicle, and one-half of the mice were crossed over after initial treatment to the opposite group. L-744,832 induced reversible regression of mammary tumors that was paralleled by a decrease in serum levels of TGF alpha secreted by the tumor cells. There was no difference in response to treatment with FTI between MMTV-TGF alpha mice, in which tumorigenesis was accelerated by multiparity or the chemical carcinogen 7,12-dimethylbenzanthracene, and MMTV-TGF alpha/neu mice. The tumor histological type had no impact on FTI sensitivity. For mechanistic analyses, tumor excision biopsies were obtained from 12 mice before and after treatment with L-744,832. In these samples, tumor regression was paralleled biochemically by inhibition of mitogen-activated protein kinase activity and biologically by an increase in G1-phase and decrease in S-phase fractions, as well as induction of apoptosis. These results suggest that the potential clinical use of FTI could be expanded to include cancers harboring activated receptor tyrosine kinases as well as those containing activated Ras.

Alkyl and Aryl Transferases↗
PubMed1998

Dominant-negative interference of the transforming growth factor beta type II receptor in mammary gland epithelium results in alveolar hyperplasia and differentiation in virgin mice.

Transforming growth factor (TGF)-beta1 and TGF-beta3 are normally expressed at high levels in the mammary gland during quiescence and at all stages of development, except lactation. Exogenously added TGF-beta1, -beta2, and -beta3 have been shown to regulate growth and differentiation of mammary epithelial cells in vitro and in vivo. TGF-betas signal through a heteromeric complex of type I and type II serine/threonine kinases. The type II receptor is necessary for ligand binding and growth suppression by TGF-betas. Deletions of the cytoplasmic domains of several kinase receptors known to function in multimeric complexes have been shown to act as dominant-negative mutations. To evaluate the role of endogenous TGF-betas in the growth and differentiation of the mammary gland in vivo, we have targeted expression of a truncated, kinase-defective TGF-beta type II receptor to mammary epithelial cells in transgenic mice using the mouse mammary tumor virus promoter/enhancer. Transgene expression was localized to the epithelial cells of terminal ducts and alveolar buds. At approximately 20 weeks of age, virgin female transgenic mice demonstrated varying degrees of mammary epithelial hyperplasia. Mammary glands from transgenic, virgin animals exhibited alveolar development and expression of the milk protein, beta-casein. The data suggest that impaired responsiveness in the epithelium to endogenous TGF-betas results in inappropriate alveolar development and differentiation in the mammary gland. We conclude that endogenous TGF-betas signal to the epithelium to maintain quiescence in the mammary glands of virgin animals.

Animals↗
PubMed1995

Expression of heat shock genes in Clostridium acetobutylicum.

Characterization of the heat shock response in Clostridium acetobutylicum has indicated that at least 15 proteins are induced by a temperature upshift from 30 to 42 degrees C. These so-called heat shock proteins include DnaK and GroEL, two highly conserved molecular chaperones. Several genes encoding heat shock proteins of C. acetobutylicum have been cloned and analysed. The dnaK operon includes the genes orfA (a heat shock gene with an unknown function), grpE, dnaK, and dnaJ; and the groE operon the genes groES and groEL. The hsp18 gene coding for a member of the small heat shock protein family constitutes a monocistronic operon. Interestingly, the heat shock response in this bacterium is regulated by a mechanism, which is obviously different from that found in Escherichia coli. So far, no evidence for a heat shock-specific sigma factor of the RNA polymerase in C. acetobutylicum has been found. In this bacterium, like in many Gram-positive and several Gram-negative bacteria, a conserved inverted repeat is located upstream of chaperone/chaperonin-encoding stress genes such as dnaK and groEL and may be implicated as a cis-acting regulatory site. The inverted repeat is not present in the promoter region of hsp18. Therefore, in C. acetobutylicum there are at least two classes of heat shock genes with respect to the type of regulation. Evidence has been found that a repressor is involved in the regulation of the heat shock response in C. acetobutylicum. However, this regulation seems to be independent of the inverted repeat motif, and the mechanism by which the inverted repeat motif mediates regulation remains to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Outcomes of treatment of socially rehabilitated methadone maintenance patients in physicians' offices (medical maintenance): follow-up at three and a half to nine and a fourth years.

OBJECTIVE: To determine whether selected socially rehabilitated former heroin addicts maintained on methadone can continue successful rehabilitation while maintained on methadone by primary care physicians rather than licensed clinics. This procedure has been termed "medical maintenance." DESIGN: Cohort study with 42-111 months of follow-up. SETTING: Offices of hospital staff physicians (internists or family practitioners). PATIENTS: The 100 patients met extensive entry criteria, including five or more years in conventional methadone maintenance treatment; stable employment or other productive activity; verifiable financial support; and no criminal involvement, use of illegal drugs, or excessive alcohol use within three or more years. MEASUREMENTS AND MAIN RESULTS: Outcome measures used were retention in treatment, discharge for one of several reasons, lost medication incidents, and substance abuse. At one, two, and three years of treatment, 98, 95, and 85 patients, respectively, remained in medical maintenance. Cumulative proportional survival in treatment was 0.735 +/- 0.048 at five years and 0.562 +/- 0.084 at nine years. After 42-111 months, 72 patients remained in good standing; 15 patients had unfavorable discharges (11 for cocaine use, three for misuse of medication, and one for administrative violations); seven voluntarily withdrew from methadone in good standing (after receiving it for 9.1-24.4 years); four died; one transferred to a chronic care facility; and one voluntarily left the program. CONCLUSIONS: Carefully selected methadone maintenance patients in medical maintenance have a high retention rate and a low incidence of substance abuse and lost medication. Voluntary withdrawal from methadone maintenance after one or two decades is possible. The authors believe that medical maintenance should be made available to appropriate patients in other localities.

Adult↗