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Biomedical subjects

B Rubin

Publications and source records attributed to B Rubin.

At least 55 records · Page 3Linked to original sources
PubMed1996

Comparison of nonrandomized trials with slow-release sodium fluoride with a randomized placebo-controlled trial in postmenopausal osteoporosis.

The results of slow-release sodium fluoride (SR-NaF) treatment in two nonrandomized trials involving 65 patients with postmenopausal osteoporosis from the primary site and 121 patients from collaborative sites were compared with those obtained from 54 treated patients and 56 patients taking placebo from a randomized controlled trial. Spinal fracture data were analyzed separately in mild to moderate bone loss of lumbar spine (baseline L2-L4 bone density [BD] > or = 65% young normal) and in severe bone loss (BD < 65%). Since demographic and fracture data were similar among fluoride-treated patients from the three trials at each stratum of bone loss, their data were combined. In mild to moderate bone loss, SR-NaF treatment in the combined group virtually eliminated new spinal fractures with 96.6% of patients remaining fracture-free. The Fluoride group had a markedly lower individual vertebral fracture rate (0.025 vs. 0.188/patient year, p = 0.0001) and group vertebral fracture rate (0.029 vs. 0.175/patient year, relative risk [RR] 0.12, p = 0.0001) than the Placebo group. In severe bone loss, the combined treated group had a significantly lower new spinal fracture rate than the Placebo group, although the differences were not as marked (group vertebral fracture rate of 0.150 vs. 0.276/patient year, RR 0.54, p = 0.03). In the combined fluoride-treated group, the L2-L4 bone mass rose by 4-6%/year for 4 years, and the femoral neck BD increased by 1-2%/year during first 2 years. The radial shaft BD did not change. The Placebo group did not show a change in bone mass at any site. The prevalence (percentage) of patients with related gastrointestinal side effects and nonvertebral fracture rates did not differ significantly between the combined SR-NaF group and the Placebo group (hip fracture rate of 0.0045/patient year in SR-NaF and 0.0053/patient year in Placebo; appendicular fracture other than hip (see text) rate of 0.0193/patient year in SR-NaF and 0.0159/patient year in Placebo). A subgroup analysis showed a low baseline L2-L4 BD, high prevalent spinal fractures, and reduced body weight to be important determinants of the development of spinal fracture during SR-NaF treatment. Concomitant medications (estrogen, vitamin D, thiazide and thyroid hormone) were not independent predictors of the spinal fracture risk. Only 17% of fluoride-treated patients were nonresponders (new spinal fractures or a fall/no change in L2-L4 bone mass). Thus, the effects of SR-NaF treatment on the spinal fracture rate from nonrandomized trials were similar to those of the treated group of the randomized trial but different from those of the Placebo group. The similarity of response of nonrandomized trials with that of the randomized controlled trial and the resultant combined analysis further validate the efficacy and safety of SR-NaF in the treatment of postmenopausal osteoporosis.

Bone Density↗
PubMed1996

Tobacco use prevalence and correlates among adolescents in a clinician initiated tobacco prevention trial in California, USA.

OBJECTIVES: Baseline data for the clinician initiated, tobacco prevention trial, the first non-school based clinician mediated tobacco prevention study, were used to explore the degree to which young people receiving orthodontic treatment use tobacco and the differences in use rates between national, California, and patient samples. Correlates of tobacco use were identified and these correlates were contrasted with findings from the published reports. DESIGN AND SETTING: A 26 item telephone survey assessed demographic information, tobacco use, selected health related behaviours, and variables based on social learning theory. The study was conducted among 11 to 18 year old orthodontic patients from San Diego, Orange, Riverside, San Bernardino, and Los Angeles Counties, California, USA. PARTICIPANTS: Of the 17925 patients who were eligible, 16915 (> 94%) completed the survey. MEASUREMENTS AND MAIN RESULTS: Multivariate analyses were conducted using a logistic mixed effects model. Although the 30 day prevalence rate of tobacco use (6%, n = 1010) proved lower than California and national samples, the rates for the age, gender, and race ethnicity subgroups showed trends similar to those seen in California and national samples. Ten variables were significantly associated with tobacco use (p < 0.05), including 30 day alcohol use (OR = 7.88), age (OR = 1.32), and living with a tobacco user (OR = 1.72). CONCLUSIONS: Because 6% of orthodontic patients use tobacco, interventions are warranted to reach the health "Objectives for the Nation". Patterns of correlates of tobacco use were essentially the same for orthodontic patients, California, and national samples, suggesting that these associations are generalisable.

Adolescent↗
PubMed1996

An adolescent tobacco-use prevention trial in orthodontic offices.

OBJECTIVES: This study examined the effect of an orthodontist-delivered tobacco-use prevention program for adolescents. METHODS: Southern California orthodontic offices were randomly assigned to experimental (n = 77) and control (n = 77) groups. Randomly selected adolescents were interviewed at baseline and 2 years later (n = 15,644). Experimental offices received tobacco prevention training, anti-tobacco materials, and 50 cents for each anti-tobacco "prescription" written. RESULTS: The 30-day tobacco use 2-year incidence rates for the control and experimental groups were 12.6% and 12.0%, respectively; incidence rates for using tobacco more than 100 times were 7.6% and 6.8%. Differences between the groups did not reach significance. Mean prescription compliance was 64.4%. A multivariate logistic model, showed a significant dose response: patients who received more prescriptions had lower incidence rates than those who received few or none (10% vs 14%). CONCLUSIONS: Training, payment, and support did not ensure clinician compliance with prevention services. The dose effect suggests that replication under conditions that would ensure clinician compliance and statistical power would more thoroughly test clinicians' ability to prevent tobacco use.

Adolescent↗
PubMed1995

Inhibition of matrix metalloproteinases by hydroxamates containing heteroatom-based modifications of the P1' group.

In this study, structure-based drug design of matrix metalloproteinase inhibitors [human fibroblast collagenase (HFC), human fibroblast stromelysin (HFS), and human neutrophil collagenase (HNC)] was utilized in the development of potent hydroxamates which contain novel, heteroatom-based modifications of the P1' group. A series containing a P1' butyramide group resulted in a nanomolar potent and selective HNC inhibitor as well as a dual HFS/HNC inhibitor. Benzylic ethers with a four- or five-carbon methylene linker in the P1' position also produced nanomolar potent HFS/HNC inhibition and micromolar potent HFC inhibition as expected. Surprisingly, the phenolic ethers of the same overall length as the benzylic ethers showed nanomolar potencies against HFC, as well as HFS and HNC. The potency profile of the phenolic ethers was optimized by structure-activity relationships of the phenolic group and the C-terminal amide. These inhibitors may help elucidate the in vivo roles of matrix metalloproteinases in normal and disease states.

Crystallography, X-Ray↗
PubMed1995

Double-blind comparison of zopiclone and flunitrazepam in elderly insomniacs with special focus on residual effects.

In a double-blind study of 102 patients with a mean age of 79 years, zopiclone was compared to flunitrazepam. The patients rated their sleep in a diary. There was no statistically significant difference between the relatively low dose of 5 mg zopiclone and 1 mg flunitrazepam for eleven out of the twelve variables measuring subjective sleep quality and quantity. There was no differences between the drugs as regards patients' feelings of being rested or alertness.

Aged↗
PubMed1995

Intra-arterial infusion of urokinase for acute, critical ischemia in the lower limb.

OBJECTIVE: To assess the value of intra-arterial urokinase infusion in the management of acute, critical ischemia of the lower limb. DESIGN: A prospective study. SETTING: A vascular surgery department within a university hospital. PATIENTS: Twenty-five consecutive patients with acute, critical ischemia of the lower limb, excluding those requiring immediate surgical intervention. Follow-up ranged from 1 to 18 months. INTERVENTION: Angiography followed by intra-arterial infusion of urokinase. MAIN OUTCOME MEASURES: Angiographic and clinical evidence of clot lysis and limb reperfusion, any surgical procedures required and final clinical outcome. RESULTS: Urokinase was technically successful in lysing clot in 19 patients: 7 required no further treatment; in 8 an underlying lesion was identified and repaired by either percutaneous angioplasty or surgery; in the remaining 4 patients, although the clot was lysed, the limbs remained ischemic and, since reconstruction was considered impossible, amputation was required. Two patients improved clinically with little angiographic evidence of clot lysis. A total of nine patients required amputation, seven of these as a "primary" procedure after urokinase infusion. There were four episodes of significant morbidity but no deaths. CONCLUSION: Urokinase has a place in the management of acute vascular occlusion of the lower limb, not only in treating the occlusion but, equally importantly, in facilitating identification of lesions that require surgical intervention.

Acute Disease↗
PubMed1994

Functionally important amino acids in the TCR revealed by immunoselection of membrane TCR-negative T cells.

A spontaneous TCR cell surface variant (3P11) of the Jurkat T cell line is described and characterized. 3P11 was selected by incubation of Jurkat cells with anti-TCR mAb followed by passage through Ig anti-Ig columns and cloning. 3P11 contained mRNA for both Ti alpha and Ti beta and CD3 gamma, delta, epsilon and zeta. Biochemical analyses demonstrated that all of the TCR components were produced in 3P11 cells. The Ti alpha beta/CD3 gamma delta epsilon zeta complex was assembled in the endoplasmic reticulum but the zeta did not associate with this complex. Epitopes recognized by the Ti beta chain specific mAb beta F1 and JOVI as well as anti-V beta 8 were affected in the 3P11 Ti beta chain indicating that the 3P11 Ti beta chain was mutated. Transfection of a wild-type Ti beta cDNA into 3P11 cells reconstituted TCR expression. Sequence analyses of the 3P11 Ti beta chain demonstrated a guanine to adenine change in the second nucleotide of the triplet coding for cysteine191 resulting in a cysteine to tyrosine exchange. Cysteine191 is the C-terminal cysteine involved in the intrachain disulfide bond in the C domain of the Ti beta chain; thus, the 3P11 Ti beta chain did not contain this disulfide bond. Transfection of a site-directed Ti beta chain containing the 3P11 mutation into a Ti beta negative variant of the Jurkat cell line resulted in a TCR phenotype identical with 3P11 demonstrating that the mutation identified in the 3P11 Ti beta chain was the sole cause for the 3P11 defect.

Amino Acid Sequence↗
PubMed1994

Structure of human neutrophil collagenase reveals large S1' specificity pocket.

The crystal structure of the catalytic domain of human neutrophil collagenase complexed with a peptide transition state analogue has been determined to a resolution of 2.1 A. The structure of the neutrophil enzyme, when compared with the three dimensional structure of the corresponding human fibroblast collagenase, shows differences in the first, S1', of the three enzyme specificity subsites on the carboxy-terminal side of the substrate scissile bond. The S1' pocket in the neutrophil collagenase is significantly larger than the equivalent site in the fibroblast enzyme, suggesting that the former enzyme has a broader range of possible substrates. Such differences also suggest approaches for the design of selective matrix metalloproteinase inhibitors.

Amino Acid Sequence↗
PubMed1994

Lack of restricted T-cell receptor beta-chain variable region (V beta) usage of reactive T-lymphocytes in Hodgkin's disease.

T-cell response against tumour-associated antigens is mediated by the TCR complex. To determine a possibly restricted TCR-V beta repertoire in reactive T-lymphocytes in Hodgkin's disease (HD), 20 cases (of which 10 were EBV-positive cases) were investigated using 14 monoclonal antibodies (MoAbs) recognizing 11 different TCR-V beta region family products and Northern blot analysis with cDNA probes specific for mRNA transcripts of 11 V beta families that were not detectable by MoAbs. Four V beta families (V beta 5, V beta 6, V beta 8, V beta 19) were investigated using both immunohistochemistry (IHC) with anti-V beta MoAbs and Northern blot analysis. Immunohistochemical and Northern blot findings were correlated with the detection of the Epstein-Barr virus (EBV) genome in Hodgkin's and Reed-Sternberg cells (H-RS). The non-neoplastic lymphocytes in HD were predominantly of T-phenotype (CD3+). Most of these cells were TCR-alpha beta+ (beta F1+) and only a few T-cells were reactive for TCR-delta 1 antibody (TCR-gamma delta+). In the majority of cases helper/inducer T-cells (CD4+) outnumbered suppressor/cytotoxic T-cells (CD8+). Labelling of these samples with the panel of 14 anti-V beta MoAbs showed that only a small percentage (0.2-5.5%) of beta F1+ lymphocytes were positive with each of these MoAbs. The proportion of these cells was comparable to that seen in normal tissues. Most TCR V beta+ cells were randomly distributed, but in virtually all cases occasional V beta+ cells pertaining to the various V beta families were seen in close contact to H-RS cells. Using total RNA extracted from malignant and normal tissues, no visible band was detected with the various V beta probes. As determined in the present study, the percentage of T-cells expressing a given V beta family must be > or = 10% to be detected with Northern blot. Thus, the percentage of V beta+ cells expressing V beta families which were explored only with Northern blot were within the same range as those of the 11 different TCR-V beta region families assessed with IHC, i.e. 1-10% of lymphoid cells. The results of the present study show that in HD there is no restricted T-cell V beta repertoire usage regardless of the detection of EBV. In addition, since the various V beta families are represented in T-cell subpopulations forming rosettes around H-RS cells, we conclude that the T-cells attracted by H-RS cells constitute a polyclonal population.

Antigens, Neoplasm↗
PubMed1994

A highly conserved phenylalanine in the alpha, beta-T cell receptor (TCR) constant region determines the integrity of TCR/CD3 complexes.

In the present study, we have investigated the importance of a phenylalanine (phe195) in the Tcr-C alpha region on Tcr-alpha,beta/CD3 membrane expression. An exchange of phe195 with a tyrosine residue does not affect Tcr/CD3 membrane expression; however, exchange with aspartic acid, histidine or valine prohibit completely Tcr/CD3 membrane expression. This seems to be due to a lack of interaction between mutated Tcr-alpha,beta/CD3-gamma epsilon,delta epsilon complexes and zeta 2 homodimers. The Tcr-C alpha region around phe195 seems together with the same region in the Tcr-C beta region to constitute an interaction site for zeta 2 homodimers. The presence of phe195 on both Tcr-C alpha and Tcr-C beta causes high avidity interaction with zeta 2 homodimers, whereas his195 in both Tcr-C gamma and Tcr-C delta results in an apparently lower avidity interaction with zeta 2 homodimers. It is suggested that the phe195 region (on beta-strand F) and eventually adjacent aromatic amino acid residues on beta-strand B region may play an important role in Tcr-alpha,beta/CD3 membrane expression, in Tcr-alpha,beta/CD3 competition with Tcr-gamma,delta/CD3 complexes for zeta 2 homodimers and in the control of formation of 'mixed' Tcr heterodimers.

Amino Acid Sequence↗
PubMed1994

[Epstein-Barr virus replication in Hodgkin disease].

Epstein-Barr virus (EBV) is present in up to 40% of Hodgkin's disease (HD). The viral genomes remain latent within Reed-Sternberg cells (RS cells), but the recent detection of Zebra protein in rare neoplastic cells of a few EBV+ HD cases, suggests an activation of EBV replication. We have studied fifty HD cases containing EBV genomes and expressing LMP1 protein (including five AIDS-related cases), by immunohistochemistry with anti-Zebra antibodies. Four of these cases (all HIV-) showed Zebra+ tumor cells. One of these four cases showed numerous Zebra+ neoplastic cells (approximately 1% of tumor cells) and positive staining for EA-R protein, thus indicating early gene expression. In situ hybridization with biotinylated BamHI W probe revealed in this case, a signal of unusual strength within some Reed-Sternberg cells, probably related to increased number of EBV genomes, thus suggesting EBV replication. Viral replication was finally confirmed in this case, by the detection of BLLF1 transcripts (encoding for the membrane antigen gp 350/220) using reverse transcriptase and polymerase chain reaction. Thus, a very few Zebra+ neoplastic cells are concerned by viral replication, most of them harboring EBV involved in an abortive, instead of a full lytic cycle. EBV replication in RS cells remains an exceptional event, but may provide clues to immunologic mechanisms of control of viral latency. Clinical implications need further investigations.

Adult↗
PubMed1994

[Study of the membrane expression of TcR/CD3 complex using somatic cell mutants].

T lymphocytes express membrane antigen receptor TcR/CD3 complexes only when all subunits are correctly assembled. Studies on TcR/CD3 membrane negative T cell variants containing all necessary subunits intracellularly, may allow to identify amino acids important for different subunit interactions. In this review, we summarize our recent work on TcR/CD3 negative variants of the human T cell line Jurkat. We found two critical amino acids in the TcR-alpha and TcR-beta extracellular constant regions (phenylalanine n. 216 and intrachain disulfide cysteine n. 212) involved in TcR-alpha beta/CD3- gamma epsilon, delta epsilon intermediary complex/zeta 2 homodimer interactions: (1) amino acid exchanges of phenylalanine demonstrated the importance of an aromatic amino acid residue at this position; (2) the intrachain disulfide bond assures a tertiary structure of the constant domain that is necessary for association with zeta 2 homodimers.

Amino Acid Sequence↗
PubMed1993

Demonstration of Epstein-Barr virus replication in Reed-Sternberg cells of Hodgkin's disease.

Epstein-Barr virus (EBV) is detectable in approximately 40% of cases of Hodgkin's disease (HD). The viral genomes remain latent but positive staining with anti-ZEBRA antibody in a small fraction of Reed-Sternberg (RS) cells of some cases of HD would suggest possible activation of EBV replication within these cells. We report the investigation of 40 cases of EBV-associated HD (including 5 human immunodeficiency virus [HIV]-positive cases) using anti-ZEBRA antibodies. Positive staining was found in only three (HIV-negative) cases. One of these three cases showed approximately 1% of ZEBRA-positive tumor cells, whereas the other two cases showed rare positive cells. In the case with 1% ZEBRA-positive cells, a strong signal was obtained with anti-EA-R antibody and BHLF1 oligoprobes, which indicated early gene expression. EBV replication could be shown in this case by nonisotopic in situ DNA-DNA hybridization, which showed markedly increased numbers of EBV genomes in a few RS cells. Viral replication was confirmed using reverse transcriptase and polymerase chain reaction that detected transcripts from the BLLF1 gene encoding for the membrane antigen gp350/220. EBV replication in RS cells seems to be an exceptional event but may provide clues to mechanisms of control of viral latency and assume clinical implications in the future.

Base Sequence↗
PubMed1993

Insights into interfacial activation from an open structure of Candida rugosa lipase.

The structure of the Candida rugosa lipase determined at 2.06-A resolution reveals a conformation with a solvent-accessible active site. Comparison with the crystal structure of the homologous lipase from Geotrichum candidum, in which the active site is covered by surface loops and is inaccessible from the solvent, shows that the largest structural differences occur in the vicinity of the active site. Three loops in this region differ significantly in conformation, and the interfacial activation of these lipases is likely to be associated with conformational rearrangements of these loops. The "open" structure provides a new image of the substrate binding region and active site access, which is different from that inferred from the structure of the "closed" form of the G. candidum lipase.

Amino Acid Sequence↗
PubMed1993

A masked, randomized, dose-response study between cyclosporine A and G in the treatment of sight-threatening uveitis of noninfectious origin.

Thirty-two patients with sight-threatening uveitis and a decrease in visual acuity requiring systemic therapy were randomly assigned to either cyclosporine A or G in a dose-escalation study. Groups received from 2.5 mg/kg of body weight/day to 10 mg/kg of body weight/day of either drug along with low-dose prednisone. More patients taking cyclosporine G had improved visual acuity and a decrease in macular edema, which occurred more rapidly than in the other group, even at the lower doses tested. No difference in renal function was noted between groups at any doses tested. Four patients receiving cyclosporine G had hepatic alterations, but only one required cessation of the drug. The study indicates the potential usefulness of cyclosporine G, particularly at lower doses (4 mg/kg of body weight/day), which could lower the potential for serious renal complications.

Adult↗
PubMed1993

Characterization of T cell receptor assembly and expression in a Ti gamma delta-positive cell line.

T cell antigen receptor (TcR) heterodimers of both the Ti-alpha beta and Ti-gamma delta types are expressed at the surface of T cells noncovalently associated with the CD3 complex composed of the monomorphic chains gamma, delta, epsilon and zeta. The structural relationship and assembly of the various components of this multimeric protein complex is still not fully understood. In this report, the human leukemic T cell line Lyon which expresses a Ti-gamma delta/CD3 complex, was characterized and compared to another human leukemic T cell line Jurkat (Ti-alpha beta/CD3). Membrane TCR-/CD3- variants of the T cell Lyon were induced and found to produce all of the Ti/CD3 components, with the exception of Ti-delta. Biochemical analysis indicated that: (1) Ti-gamma/CD3 gamma, delta, epsilon complexes were formed in the endoplasmic reticulum in the absence of Ti-delta; (2) the CD3-zeta chain did not associate with the Ti-gamma/CD3 gamma delta epsilon complex and (3) the Ti-delta chain was required for cell surface expression of the Ti-gamma delta/CD3 complex. Introduction of Jurkat wild-type Ti-alpha cDNA into Lyon T cells resulted in Ti-alpha beta/CD3 expression and abrogated Ti-gamma delta/CD3 expression. In contrast, the expression of the Ti-gamma delta/CD3 complex was not affected by transfection of a mutated Ti-alpha cDNA into Lyon cells. The mutated Ti-alpha chain formed complexes with Ti-beta and CD3 gamma delta epsilon, but the CD3-zeta chain did not associate with these complexes. Taken together analysis of Lyon cells transfected with either wild-type or mutated Ti-alpha suggested that the CD3-zeta chain may have higher affinity for Ti-alpha beta/CD3 complexes than for Ti-gamma delta/CD3 complexes.

Biological Transport↗