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Biomedical subjects

L Goldberg

Publications and source records attributed to L Goldberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

Polymorphism in the human anti-pig natural antibody repertoire: implications for antigen-specific immunoadsorption.

BACKGROUND: Anti-Galalpha1-3Gal antibodies cause hyperacute rejection (HAR) in pig-to-primate xenotransplantation. Long-term graft survival has not been achieved despite abrogation of HAR using transgenic pigs. IgG and IgM anti-Galalpha1-3Gal also play a role in the events following abrogation of HAR. Characterizing these antibodies and developing a system for their removal is therefore crucial to future success in xenotransplantation. METHODS AND RESULTS: We have developed a neoglycoprotein enzyme-linked immunosorbent assay to probe the precise antigenic requirements for the binding of anti-Galalpha1-3Gal and have analyzed 77 normal sera. Sixty-six percent of individuals have IgG that recognizes the Galalpha1-3Gal di-, tri-, and pentasaccharides (D, T, and P, respectively), termed DTP phenotype. The frequency of other phenotypes was - -P, 13%; -TP, 12%; D-P, 8%; and DT-, 1%. The IgG subclasses found were IgG2 (95%), IgG3 (34%), IgG1 (31%), and IgG4 (17%). IgM in 91% of individuals recognized all three antigens. Further antibody heterogeneity was demonstrated when immunoadsorbents derived from Galalpha1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc (PENTA) were tested. Galalpha1-3Galbeta1-4Glc (TRI 6) or PENTA agarose were effective for IgG removal in all individuals. For IgM removal, two deoxy derivatives were completely successful in 73% of individuals. Combining the Galalpha1-3Gal (DI) and TRI 6 agarose produced an adsorbent that completely removed anti-Galalpha1-3Gal IgG and IgM in all individuals tested. CONCLUSIONS: Although the polymorphism in the anti-Galalpha1-3Gal repertoire, which we have demonstrated, represents a major obstacle to the development of an effective immunoadsorbent, the combination of DI and TRI 6 agarose appears sufficient for pig-to-human xenotransplantation.

Animals↗
PubMed1997

Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents.

The alpha7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) is abundantly expressed in hippocampus and is implicated in modulating neurotransmitter release and in binding alpha-bungarotoxin (alpha-BGT). A null mutation for the alpha7 subunit was prepared by deleting the last three exons of the gene. Mice homozygous for the null mutation lack detectable mRNA, but the mice are viable and anatomically normal. Neuropathological examination of the brain revealed normal structure and cell layering, including normal cortical barrel fields; histochemical assessment of the hippocampus was also normal. Autoradiography with [3H]nicotine revealed no detectable abnormalities of high-affinity nicotine binding sites, but there was an absence of high-affinity [125I]alpha-BGT sites. Null mice also lack rapidly desensitizing, methyllycaconitine-sensitive, nicotinic currents that are present in hippocampal neurons. The results of this study indicate that the alpha-BGT binding sites are equivalent to the alpha7-containing nAChRs that mediate fast, desensitizing nicotinic currents in the hippocampus. These mice demonstrate that the alpha7 subunit is not essential for normal development or for apparently normal neurological function, but the mice may prove to have subtle phenotypic abnormalities and will be valuable in defining the functional role of this gene product in vivo.

Aconitine↗
PubMed1997

The efficacy and safety of Skinner herpes simplex vaccine towards modulation of herpes genitalis; report of a prospective double-blind placebo-controlled trial.

A randomised, placebo-controlled, multi-centre trial of intracellular subunit herpes simplex virus (HSV) type 1 vaccine NFU.Ac.HSV-1(S-)MRC (Skinner vaccine) was conducted at three medical centres in the United States. Subjects with documented herpes genitalis of at least 1-year duration and a history of six or more genital HSV recurrences in the 12 months prior to study entry were randomised to receive vaccine or placebo at 0, 1 and 2 months. Vaccination induced significant neutralising, enzyme-linked immunosorbent assay and lymphocyte transformation response to HSV-1 antigen. The frequency of recurrences was reduced in the vaccinated female patients at both 3 and 6 months following vaccination with an overall reduction in patients of both sexes which did not reach statistical significance. Recurrence severity was reduced as measured by decreased number of lesions and associated symptoms per recurrence (P = 0.04). The data suggest that clinical manifestations of latent HSV genital infection may be modified by therapeutic immunisation.

Adult↗
PubMed1996

Effects of a multidimensional anabolic steroid prevention intervention. The Adolescents Training and Learning to Avoid Steroids (ATLAS) Program.

OBJECTIVE: To test a team-based, educational intervention designed to reduce adolescent athletes' intent to use anabolic androgenic steroids (AAS). DESIGN: Randomized prospective trial. SETTING: Thirty-one high school football teams in the Portland, Ore, area. PARTICIPANTS: Seven hundred two adolescent football players at experimental schools; 804 players at control schools. INTERVENTION: Seven weekly, 50-minute class sessions were delivered by coaches and student team leaders, addressing AAS effects, sports nutrition and strength-training alternatives to AAS use, drug refusal role play, and anti-AAS media messages. Seven weight-room sessions were taught by research staff. Parents received written information and were invited to a discussion session. MAIN OUTCOME MEASURES: Questionnaires before and after intervention and at 9- or 12-month follow-up, assessing AAS use risk factors, knowledge and attitudes concerning AAS, sports nutrition and exercise knowledge and behaviors, and intentions to use AAS. RESULTS: Compared with controls, experimental subjects at the long-term follow-up had increased understanding of AAS effects, greater belief in personal vulnerability to the adverse consequences of AAS, improved drug refusal skills, less belief in AAS-promoting media messages, increased belief in the team as an information source, improved perception of athletic abilities and strength-training self-efficacy, improved nutrition and exercise behaviors, and reduced intentions to use AAS. Many other beneficial program effects remained significant at the long-term follow-up. CONCLUSIONS: This AAS prevention program enhanced healthy behaviors, reduced factors that encourage AAS use, and lowered intent to use AAS. These changes were sustained over the period of 1 year. Team-based interventions appear to be an effective approach to improve adolescent behaviors and reduce drug use risk factors.

Adolescent↗
PubMed1996

The Adolescents Training and Learning to Avoid Steroids (ATLAS) prevention program. Background and results of a model intervention.

OBJECTIVE: To develop and test a school-based intervention to prevent anabolic androgenic steroid use among high-risk adolescent athletes. DESIGN: Nonrandom controlled trial. SETTING: Two urban high schools. PARTICIPANTS: Fifty-six adolescent football players at the experimental school and 24 players at the control school. INTERVENTION: Eight weekly, 1-hour classroom sessions delivered by the coach and adolescent team leaders, and eight weight-room sessions delivered by research staff. The intervention addressed sports nutrition and strength training as alternatives to steroid use, drug refusal role play, and antisteroid media campaigns. OUTCOME MEASURES: A preintervention and postintervention questionnaire that assessed attitudes toward and intent to use steroids and other drugs; knowledge of drug effects; and diet, exercise, and related constructs. RESULTS: Compared with controls, experimental subjects were significantly less interested in trying steroids after the intervention, were less likely to want to use them even if their friends used them, were less likely to believe steroid use was a good idea, believed steroids were more dangerous, had better knowledge of alternatives to steroid use, had improved body image, increased their knowledge of diet supplements, and had less belief in these supplements as beneficial. CONCLUSIONS: Significant beneficial effects were found despite the sample size, suggesting that the effects of the intervention was large. This outcome trial demonstrates an effective anabolic androgenic steroid prevention program for adolescent athletes, and the potential of team-based interventions to enhance adolescents' health.

Adolescent↗
PubMed1996

Quinolone resistance in Oligella urethralis-associated chronic ambulatory peritoneal dialysis peritonitis.

Oligella urethralis is an organism which is normally isolated as a commensal from the genitourinary tract. We describe the first two reported cases of CAPD-associated peritonitis caused by this organism. Both isolates were found to be resistant to ciprofloxacin, while relatively sensitive to a wide range of antimicrobial drugs. These findings indicate that this organism may be an opportunistic pathogen for CAPD patients, and that extensive ciprofloxacin usage provides a selection pressure for emergence of resistance.

Adult↗
PubMed1996

Outcome measures, pooled index and quality of life instruments in rheumatoid arthritis.

BACKGROUND AND OBJECTIVE: A variety of outcome measures are used in evaluating disease activity and therapeutic efficacy in rheumatoid arthritis (RA) studies, and this makes comparisons of drug efficacy difficult. Some of the endpoints used are not standardized and/or are insensitive to change. The purpose of this report is to present a critical appraisal of outcome measures and quality of life assessments in RA studies. METHOD: An overview of the literature was undertaken to determine the extent to which there is consensus among experts in this area of research. RESULTS: The data suggest that the core set of endpoints in RA clinical studies should include tender joint count swollen joint count, patients' assessment of pain, patients' and physicians' global assessments, patients' assessment of physical function and acute phase reactant level. When trials of disease-modifying antirheumatic drugs (DMARD) last for more than a year, radiography may be useful. A 'pooled index' may be valuable, and its construction is discussed. Quality of life (QoL) instruments facilitate a fuller examination of the effects of health care interventions and these should be used to complement the more traditional clinical endpoints in the core set. The instruments most commonly used in RA research are identified. CONCLUSIONS: We conclude that randomized clinical trials of treatments in RA should now ideally use the core set of clinical endpoints and validated QoL instruments for assessing safety and efficacy.

Arthritis, Rheumatoid↗
PubMed1996

Intervention and prevention of steroid use in adolescents.

Athletes with a higher intent to use anabolic steroids were similar to students who indicated no predisposition to use steroids on economic, academic, and physical measures. They had similar understandings of anabolic steroid effects, and their self-rated understandings of how to weight train and of sports nutrition were similar. In addition, the influence of the coaches and the media and the perceived prevalence of anabolic steroid use were not different between the higher- and lower-intent students. These results demonstrated several significant differences. Higher-intent students had higher levels of alcohol and marijuana use, which suggest that those items might be tackled concurrently. These athletes had higher hostility, impulsivity, and a win-at-all-costs attitude. Despite similar physical measures, they had a high body image, but were less satisfied with their current weight. These findings underscored the importance of using nutrition and appropriate training as effective alternatives to anabolic steroids. Higher-intent students had greater peer tolerance of drug use and less parental influence not to use drugs, which implies that a peer-led small group format might be important to dispel the perceived peer tolerance. Including a parent-based component, one that emphasizes a disapproval of drug use also could be effective. Higher-intent athletes had less ability to refuse an offer of steroids. The dynamics of turning down steroids may differ from that of other illicit substances so that training in refusal skills specific to steroids is needed. These differences provide a needs assessment to identify curricular components for an intervention to permit anabolic steroid use. The sports team may be a unique educational setting because it can capitalize on peer ties, the coach's influence, and an athletes' motivation to improve, to prevent drug use, and to promote healthy behaviors.

Adolescent↗
PubMed1995

Inhibition of the pig to human xenograft reaction, using soluble Gal alpha 1-3Gal and Gal alpha 1-3Gal beta 1-4GlcNAc.

Natural anti-carbohydrate antibodies are central to hyperacute rejection in ABO-incompatible allotransplantation and in discordant xenotransplantation. ABO-incompatible rejection has been inhibited successfully using intravenous soluble carbohydrates as antibody inhibitors. The approach has been less successful previously in pig to primate xenotransplantation, where the necessary concentrations of a partial inhibitor (Gal alpha 1-6Glc) proved highly toxic. In this study, we have identified more effective inhibitors of the dominant human anti-pig antibodies that bind to the pentasaccharide Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-. The inhibitors are the terminal disaccharide (Gal alpha 1-3Gal) and terminal trisaccharide (Gal alpha 1-3Gal beta 1-4GlcNAc) of the target pentasaccharide. Twelve sera (3 from each ABO blood group) were tested in 3 different assays: lymphocytotoxic, lymphocyte flow cytometry, and solid-phase antigen ELISA. Fifty percent to 75% inhibition of human IgG and IgM was achieved using the disaccharide and trisaccharide inhibitors in the range of 10-50 mM. Disaccharide (70 mM) was used to inhibit hyperacute thrombosis in pig kidneys perfused for 40 min with heparinized human AB whole blood. The disaccharide completely inhibited red cell occlusion of glomerular but not of intertubular capillaries, although there was residual platelet thrombus in glomeruli. Disaccharide and trisaccharide can, therefore, be used in concentrations shown for other carbohydrate inhibitors to be nontoxic, for inhibition of hyperacute pig-to-human xenograft rejection. The inhibition is incomplete, however, and other antigen specificities and other rejection mechanisms are likely to be involved.

ABO Blood-Group System↗
PubMed1995

Basal cell carcinoma on the scalp of an Indian patient.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in whites, but it rarely occurs in dark persons. OBJECTIVE: To report a BCC on the hairy scalp of an Asian Indian female with no obvious risk factors except previous scalp trauma. METHODS: We review the English literature concerning BCC in Indians, and compare this with data for North American blacks and whites; and reports of BCC arising in areas of prior trauma. RESULTS/CONCLUSION: Skin cancer accounts for 1-2% of malignancies in blacks and Indians, compared with one-third of neoplasms in whites. BCC comprises 75% of skin cancers in whites, but squamous cell carcinoma represents 60-65% of skin cancers in blacks and Indians. Although most BCCs occur in sun-exposed areas in whites, blacks, and Indians, a significant percentage also develop in photoprotected areas. Trauma may be a significant risk factor for BCC, either with actinic damage or alone, as in our case.

Black People↗
PubMed1994

Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML.

Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.

Antigens, CD↗
PubMed1994

Health promotion and early disease detection among medical school faculty.

BACKGROUND: Medical school faculty members influence students' health promotion beliefs by their patient care activities and personal health habits. We characterized the medical school environment by defining faculty's health promotion and early disease detection attitudes and practices. The data disclose faculty needs and suggest a new paradigm to alter medical students' health promotion beliefs and care patterns. METHODS: An observational study of all academic faculty was conducted at a medical school using self-report survey data collected with a confidential questionnaire. The survey instrument assessed faculty demographics, 27 behaviors, and 23 beliefs concerning health promotion. RESULTS: Eighty-four percent of faculty (575 of 683) responded. Although agreement was moderate to good between lifestyle beliefs and personal behaviors, the concordance between personal adherence to and beliefs concerning the recommended physical examinations and laboratory tests was only fair (kappa 0.21 to 0.40). CONCLUSION: Faculty's health promotion and disease detection beliefs and behaviors were inconsistent. Observing this discrepancy may relate to students' establishment of attitudes and practices. Modifying faculty's personal behaviors and altering the medical school environment might enhance students' commitment toward preventive care.

Adult↗