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Biomedical subjects

H Wolfe

Publications and source records attributed to H Wolfe.

At least 19 recordsLinked to original sources
PubMed2001

Expression of galectins-1 and -3 correlates with defective mononuclear cell apoptosis in patients with juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is characterized by hyperplasia of synovial cells and accumulation of mononuclear inflammatory infiltrates, which are locally maintained through a balance between cell proliferation and apoptosis. Although defective clearance of activated T cells in RA joints has been explained by alterations of the Fas-Fas ligand system, this has not been confirmed in synovial tissue of patients with JIA. We evaluated the relation between expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) (beta-galactoside-binding proteins with pro- and anti-apoptotic properties, respectively) and the apoptosis and proliferation rates of infiltrative lymphocytes in synovial tissue of patients with JIA. METHODS: Using slide cytometry and in situ end labeling we observed dysregulated apoptosis of infiltrating mononuclear cells within the synovial tissue of patients with JIA. RESULTS: Patients with pauciarticular JIA showed minimal apoptosis, high Bcl-2 expression, and high or normal proliferation rates, while patients with polyarticular disease showed the lowest apoptotic indexes, accompanied by low Bcl-2 expression and low proliferation rates. We found that Gal-1 expression is downregulated and Gal-3 expression is upregulated in synovial tissue from patients with JIA. CONCLUSION: In patients with polyarticular JIA, accumulation of inflammatory cells is mainly due to downregulated apoptosis, whereas in patients with pauciarticular disease the process results from increased proliferation. Defective mononuclear apoptosis in synovial inflammatory infiltrates from patients with JIA could be explained in part by decreased Gal-1 and increased Gal-3 expression.

Antigens, Differentiation↗
PubMed2000

Tumor necrosis factor genetic polymorphisms correlate with infections after renal transplantation.

BACKGROUND: Nonimmunosuppressed individuals possessing a NcoI restriction enzyme site in the tumor necrosis factor (TNF) gene locus produce less TNF-alpha in vitro and in vivo than do individuals lacking this site. We have previously shown that this NcoI+/low TNF-alpha genotype is independently associated with increased rates of infection for liver transplant recipients. METHODS: In this study, we performed polymerase chain reaction amplification and restriction fragment length polymorphism analysis of the TNF locus from 45 renal transplant recipients to determine whether the presence of the NcoI site is associated with the frequency of rejection, infection, time to rejection or infection, and patient or graft survival. RESULTS: Twenty-six recipients were typed with the NcoI+/low TNF-alpha genotype, whereas 19 recipients had the NcoI-/high TNF-alpha genotype. Age, sex, donor type, secondary immunosuppression, use of anti-lymphocyte preparations, graft ischemia time, and year of transplant were evenly distributed in the two groups. There was no difference between the genotype groups in the rate of, or time to, rejection. In contrast, significantly more patients with the NcoI+/low TNF-alpha site developed infections (46% vs. 10% P=0.01). In bivari able models, each controlling for donor type, ischemia time, recipient age, use of antilymphocyte agents, and secondary immunosuppression, the NcoI+/low TNF-alpha genotype was still independently associated with increased numbers of infections (relative risk, 5.38; confidence interval, 1.20-23.8). Conclusion. We conclude that in individuals genetically predetermined to be low TNF-alpha producers, the additional inhibition of TNF-alpha production by routine immunosuppression may be excessive, rendering these individuals less able to respond to infectious stimuli. These patients may benefit from lower doses or withdrawal of corticosteroids, which are known inhibitors of TNF-alpha transcription.

Adult↗
PubMed2000

Prominent expression of mRNA for proinflammatory cytokines in synovium in patients with juvenile rheumatoid arthritis or chronic Lyme arthritis.

OBJECTIVE: To examine the cytokine profiles in synovium of patients with juvenile rheumatoid arthritis (JRA) or Lyme arthritis, 2 chronic inflammatory arthritides that affect children. METHODS: We used in situ hybridization with specific riboprobes to determine the expression of mRNA for proinflammatory or antiinflammatory cytokines in synovial samples from 5 patients with early, untreated JRA, 15 patients with late, treated JRA, and 9 patients with chronic Lyme arthritis. For comparison, synovia were examined from 6 patients with rheumatoid or psoriatic arthritis, and from 9 patients with various orthopedic conditions. RESULTS: Among the children with early, untreated JRA, a median of 3 to 8% of inflammatory cells in synovial samples expressed mRNA for the proinflammatory cytokines interleukin 1beta (IL-1beta), tumor necrosis factor-alpha(TNF-alpha), or interferon-gamma (IFN-gamma). Although a median of 3.9% of the cells expressed mRNA for the antiinflammatory cytokine IL-10, none had IL-4 mRNA. Most of the patients with late, treated JRA, chronic Lyme arthritis, rheumatoid, or psoriatic arthritis had mRNA for each of these proinflammatory cytokines in about 1% of the cells, whereas mRNA for the antiinflammatory cytokines was less frequent. The inflammatory cell density was much less in the synovium of patients with various orthopedic conditions, but about 1% of the infiltrating cells expressed mRNA for at least one of the proinflammatory cytokines. CONCLUSION: Patients with early or late JRA or chronic Lyme arthritis have expression of mRNA in synovial tissue primarily for proinflammatory cytokines, with less expression of antiinflammatory cytokines.

Adult↗
PubMed1998

Social influences: living arrangements of drug using women at risk for HIV infection.

The purpose of this study was to explore the associations among living arrangements, HIV seroprevalence, and HIV risk and protective factors among 1,322 drug users participating in the University of Miami CARES (Community AIDS Research and Evaluation Studies) HIV intervention program. Living arrangements may be associated with HIV prevention behaviors; however, these influences can be either protective or destructive and therefore merit further examination. Statistical analyses indicated differences in the living arrangements of women compared with men, and significant associations were noted among women's living arrangements, HIV seroprevalence, risk behaviors and protective behaviors. The data from this study suggest that future HIV prevention research should investigate not only high-risk individuals, but persons with whom they interact often, especially those with whom they live or with whom they have sex. The next phase of HIV and drug interventions should be attentive to the incorporation of social context and social influences, paying particular attention to understudied populations such as high-risk women.

Adult↗
PubMed1997

"Why I am not infected with HIV": implications for long-term HIV risk reduction and HIV vaccine trials.

OBJECTIVE: To describe beliefs about remaining HIV-seronegative in injecting drug users in two high-seroprevalence cities, and to consider implications of these beliefs for ongoing risk reduction efforts and for HIV vaccine efficacy trials. DESIGN: Cross-sectional survey with open- and closed-ended questions. SUBJECTS: 58 HIV-seronegative injecting drug users participating in HIV vaccine preparation cohort studies in New York City, New York, U.S.A., and Bangkok, Thailand. MAJOR FINDINGS: Large majorities of subjects in Bangkok (90%) and in New York (89%) believed their "own efforts" to practice safer injection methods and safer sex were very important in avoiding HIV infection. More Bangkok subjects (30%) believed that they would "probably" become infected with HIV in the future than New York subjects (4%). Three percent of Bangkok subjects and 70% of New York subjects believed "having an immune system strong enough to avoid becoming infected with HIV despite exposure to the virus" was very important in avoiding HIV infection. This belief in New York subjects was associated with having previously engaged in high-risk behaviors (i.e., sharing injection equipment, unprotected sex, or both) with partners known to be HIV-seropositive. CONCLUSIONS: Risk reduction programming for high-HIV-seroprevalence populations and within HIV vaccine trials should address not only specific HIV risk behaviors, but also the complex belief systems about avoiding HIV infection that develop within such groups. The person's "own efforts/self-efficacy" appears to be central in the psychology of risk reduction. Members of some high-risk populations may overestimate greatly the frequency of any possible natural immunity to becoming infected with HIV. Prevention programs for these populations will need to address explicitly the probabilistic nature of HIV transmission.

AIDS Vaccines↗
PubMed1995

Mass spectrometric identification of amino acid transformations during oxidation of peptides and proteins: modifications of methionine and tyrosine.

Liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS), tandem mass spectrometry with on-line liquid chromatography (LC/ESI-MS/MS) and high-resolution mass spectrometry with liquid secondary ionization (LSI-MS) were utilized to identify the modified amino acids in peptides and proteins formed during oxidation with performic acid. The procedure of protein oxidation was chosen to assist in protein unfolding by oxidizing the cystines to cysteic acids to allow for more complete proteolytic digestion and to create additional cleavage sites for endoproteinase Asp-N. Investigation of the Asp-N peptide map of oxidized superoxide dismutase (SOD) by LC/ESI-MS revealed that an expected proteolytic fragment of the protein was missing. In its place, two peptides with molecular weights 66 and 100 higher than that calculated for the missing peptide were observed. To identify the modified amino acids in the unexpected peptides, a model peptide with some amino acid similarities (tyrosine, arginine, methionine, lysine) to the missing peptide was chosen and was subjected to similar oxidation and enzymatic digestion steps, conditions, and reactions. After oxidation and digestion, the model peptide (TAP; sequence, Ac-MDKVLNRY) showed three major peaks in LC/MS. The peptides in the three peaks were identified as the unmodified peptide and two peptides whose molecular weights were 66 and 100 higher than that of TAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Expression of the ret proto-oncogene in phaeochromocytoma. An in situ hybridization and northern blot study.

The expression and distribution of ret proto-oncogene mRNA were investigated in five phaeochromocytomas of both familial and sporadic types by in situ hybridization (ISH) using digoxigenin-labelled cRNA probes and Northern blot (NB) analysis with random priming labelled cDNA probes. The probes corresponded to the tyrosine kinase domain of the gene. An excellent correlation was found between the ISH and NB results. By both techniques, the expression of the ret proto-oncogene was detected in three of the five cases, two of four familial tumours, and the only sporadic tumour that was studied. The results confirm that ret is frequently expressed in phaeochromocytomas and suggest that it might be an important event in their development and/or progression.

Adrenal Gland Neoplasms↗
PubMed1995

Tuberculosis knowledge among New York City injection drug users.

Structured interviews measuring tuberculosis knowledge were administered to 494 New York City injection drug users, 31% of whom reported a history of having a reactive tuberculin skin test. Medical records review of a subsample confirmed the validity of self-reported data. Most respondents understood the mechanisms of tuberculosis transmission. Three fourths of the subjects did not fully understand the distinction between a reactive skin test and active tuberculosis, but those who reported a history of skin test reactivity were twice as likely to understand this distinction. Forty percent of subjects did not understand the importance of medication adherence. Misunderstandings, based on a recent lack of tuberculosis education, may contribute to the fear and confusion that interfere with efforts to control tuberculosis.

Adolescent↗
PubMed1995

Tissue response to particulate polymethylmethacrylate in mice with various immune deficiencies.

We examined the tissue response to subcutaneous injections of particulate polymethylmethacrylate powder in fully immunocompetent C3Hf/Sed mice as well as three strains of mice with different levels of lymphocyte dysfunction. Five weeks after the injection, we found clearly demarcated granulomas. Histological and immunohistochemical studies showed that these granulomas were similar among all strains, with either paucity or absence of lymphoid cells. In situ hybridization with use of complementary RNA probes indicated that macrophages were synthesizing interleukin-1 beta messenger RNA (mRNA), a marker of macrophage activation, and a cytokine implicated in pathological bone resorption. We concluded that, in mice, there is a lymphocyte-independent pathway of macrophage activation in response to particulate polymethylmethacrylate. This suggests that the foreign-body response to particulate orthopaedic biomaterials is macrophage-initiated and maintained and that lymphocytes are not essential to this response, although they may modulate it.

Analysis of Variance↗
PubMed1994

Preparations for AIDS vaccine trials. Retention, behavior change, and HIV-seroconversion among injecting drug users (IDUs) and sexual partners of IDUs.

The likelihood that subjects in human immunodeficiency virus (HIV) vaccine efficacy trials will alter their behavioral risks for HIV infection over time must be considered in evaluating the feasibility of such trials and in estimating the necessary sample sizes to be enrolled. Potential subjects for future vaccine efficacy trials include injecting drug users (IDUs) and others who may be difficult to retain in studies and who may alter HIV-risk-related behaviors substantially over time. We have investigated behavior change, retention, and HIV seroconversion among 577 New York City resident IDUs and sexual partners of IDUs enlisted between July 1 and December 31, 1992. We attempted to see all subjects every 3 months for interviews, blood donation and HIV testing. We were able to retain 68% of subjects in the study through the third scheduled recall at 7.5-10.5 months after enlistment. HIV seroconversion through March 1, 1994, was 1.33/100 person-years at risk. There was a significant inverse relationship between HIV seroconversion and retention at the 9-month recall after adjusting for age, gender, and the amount of locator information provided by subjects at enlistment. Among subjects seen at each of the scheduled visits at 3, 6, and 9 months after enrollment, modest but statistically significant behavior changes that reduced risk were observed in self-reported drug injection frequency, heroin injection frequency, sexual contact with IDUs, and sharing of needles/syringes. The magnitude of these changes in risk, however, was small and may be transient. The behavior changes observed to date do not appear to be large enough to substantially alter calculations of sample sizes needed in future HIV vaccine efficacy trials.

AIDS Vaccines↗
PubMed1994

Intervening with high risk youth: a program model.

This paper describes a program model being implemented for older, high-risk adolescents who are beginning to exhibit significant substance use problems. The program provides an initial assessment and refers clients to appropriate services. Only a small percentage are being referred to inpatient treatment; most clients enter outpatient intervention groups, which are conducted by the program. These groups have three purposes: to allow staff to monitor and evaluate clients so that those who are in imminent danger can be placed in protective treatment settings; to help clients see themselves as candidates for recovery and to introduce them to treatment resources by accompanying them to AA and NA meetings; and to change behavior, a goal that seems more immediately achievable for youth with stable community ties who have more to lose if they get into further trouble. Besides describing the program model, this paper examines some of the difficulties of getting referrals from a variety of community agencies.

Adolescent↗
PubMed1994

Bleach use and HIV seroconversion among New York City injection drug users.

We employed a nested case-control study design to evaluate the efficacy of bleach-cleaning of needles and syringes among injecting drug users (IDUs) as a means of preventing human immunodeficiency virus (HIV) infection. Sixteen HIV-seroconverters who responded to bleach use questions and who reported injecting with shared or used equipment in the 6 months prior to their first positive visit were compared with 89 controls. Controls had remained HIV-seronegative at two or more visits, reported injecting with shared or used equipment, responded to bleach-cleaning questions, and were seen at recall visits +/- 6 months from the date of seroconversion of the index case. Risk factors associated with HIV seroconversion in univariate analyses were a history of sexual intercourse with an HIV-infected partner and the frequency of speedball (mixed heroin and cocaine) injections. After adjusting for confounders, we found no evidence that bleach use protected against HIV infection.

Adult↗
PubMed1993

HIV risk-related sexual behaviors among heterosexuals in New York City: associations with race, sex, and intravenous drug use.

OBJECTIVE: To investigate the relationship between heterosexual behaviors associated with HIV infection and ethnicity, sex, and intravenous drug use. METHODS: Subjects were recruited from Bellevue Hospital Center, New York City between 1986 and 1989, and interviewed about sexual behaviors and intravenous drug use. Analyses were based on 1561 black, white, or Hispanic individuals who reported having sexual contact with a member of the opposite sex. RESULTS: Twenty-seven per cent of the study population were black, 43% Hispanic, and 31% white. Blacks were more likely than whites or Hispanics to have initiated sexual intercourse at an early age, and to have had a sexually transmitted disease. Sex with a female drug user was more common among white men, and contact with a prostitute more frequent among Hispanic men. Among the women, Hispanics had fewer sexual risk factors overall than whites or blacks. Use of barrier contraceptives was uniformly low across all ethnic groups. Intravenous drug use was significantly associated with sexual risk-taking. Women were more likely than men to have an intravenous drug-using (IVDU) sexual partner. CONCLUSIONS: The large prevalence of high-risk sexual practices observed in this study emphasizes the continuing need to target AIDS prevention programs at those at highest risk of heterosexually transmitted HIV: racial minorities, IVDU, and their sexual partners.

Acquired Immunodeficiency Syndrome↗