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Biomedical subjects

B Rubin

Publications and source records attributed to B Rubin.

224 records · Page 13Linked to original sources
PubMedDate not supplied

The efficacy, tolerability, and safety of 1200 mg/d of oxaprozin and 1500 mg/d of nabumetone in the treatment of patients with osteoarthritis of the knee.

This 6-week, multicenter, double-masked, placebo-controlled study compared the efficacy, tolerability, and safety of the recommended starting dose of oxaprozin (1200 mg/d) and a 1500-mg/d dose of nabumetone in the treatment of patients with moderate-to-severe osteoarthritis (OA) of the knee. A total of 347 patients with a mean age of 61.1 years were randomized to receive oxaprozin (116 patients), nabumetone (115 patients), or placebo (116 patients). Adults of either sex who were older than 18 years of age were eligible for entry into the study, if they had had OA of the knee for at least 6 months. Efficacy variables included knee pain on weight bearing, knee pain on motion, patients' and physicians' global assessments of OA, pain intensity as measured on a visual analog scale, and time to walk 50 feet as quickly as possible. Efficacy variables were assessed at baseline and at weeks 1, 2, 4, and 6. Between-group differences in efficacy variables were evident by week 1. Mean improvements were significantly greater with oxaprozin than with placebo for all efficacy variables at all time periods, except knee pain on motion at weeks 2 and 4 and time to walk 50 feet at weeks 1, 2, and 4. Mean improvements were significantly greater with nabumetone than with placebo for all efficacy variables at all time periods, except the following: knee pain on weight bearing at weeks 2, 4 and 6; knee pain on motion at weeks 2 and 4; patients' global assessment at week 4; and pain intensity as measured on a visual analog scale at weeks 2 and 4. There were, however, no significant differences between oxaprozin and nabumetone in any of these efficacy variables. Adverse events were reported by 83 (71.6%) patients who took oxaprozin, by 80 (69.6%) patients who took nabumetone, and by 57 (49.1%) patients who took placebo. Adverse events were reported for significantly more patients taking oxaprozin or nabumetone than placebo. However, adverse events tended to be mild or moderate and rarely resulted in patients withdrawing from the study. Combined with the results of an earlier study, the results of this study showed that a 1500-mg/d dose of nabumetone, which is higher than the recommended starting dose of 1000 mg/d, is required for efficacy equivalent to that of the recommended starting dose of oxaprozin, 1200 mg/d, in relieving the symptoms of OA. Thus nabumetone may require dosage titration from the recommended starting dose. Oxaprozin and nabumetone were found to have similar tolerability profiles, as shown by adverse-event monitoring and withdrawal rates, as well as clinically similar safety profiles, as demonstrated by physical examinations, hematologic and biochemical laboratory testing, hemoccult testing, and adverse-event monitoring and symptom assessment.

Adult↗
PubMedDate not supplied

On the role of CD3delta chains in TCRgammadelta/CD3 complexes during assembly and membrane expression.

The present study was performed in order to analyze whether T-cell receptor (TCR)/CD3 assembly, intracellular transport and surface expression are carried in a similar way in alphabeta-and gammadelta-T cells. By means of optimal immunoprecipitation conditions with 35S-methionine/cysteine- or biotin-labelled TCR/CD3 proteins from alphabeta- or gammadelta-T-lymphoma-cell lines, as well as TCRgammadelta cDNA transfectants, it was found that CD3delta chains associate less strongly with TCRgammadelta heterodimers compared to TCRalphabeta heterodimers. This preferential reactivity of CD3delta chains appears to be structural and not owing to differences in gammadelta- versus alphabeta-T-cell intracellular environments. Our results are in accordance firstly, with data from CD3delta-deficient mice, which have gammadelta-T cells but no alphabeta-T cells, secondly with the suggested role of CD3delta chains in the positive selection of alphabeta-T cells, a process apparently not followed by gammadelta-T cells, and lastly with the differential roles of CD3delta chains versus CD3gamma chains, explaining the maintenance of two CD3delta and CD3gamma genes after the duplication from a CD3delta/gamma gene present in avians. The impaired reactivity of CD3delta chains with TCRgammadelta heterodimers seems to be owing to a less efficient association with TCRgamma chains. In contrast, CD3delta chains interact as strongly with TCRdelta chains as do CD3gamma chains with both TCRgamma and TCRdelta chains. These data may explain, at the molecular levels, why surface TCR/CD3 expression levels are impaired in gammadelta-T cells from CD3gamma-deficient mice but not from CD3delta-deficient mice.

Animals↗
PubMedDate not supplied

Citrullination of self-proteins and autoimmunity.

Citrullination (deimination is an enzymatic, posttranslational conversion of arginine residues to citrulline residues) of joint-associated self-proteins may be a possible mechanism in the induction of autoimmune CD4 T-cell responses in rheumatoid arthritis. We have studied the immune response to normal or deiminated human fibrinogen (hFBG) in mouse strains expressing major histocompatibility complex (MHC) class II antigens similar to either RA-susceptible or non-susceptible HLA-DR4 alleles. Upon immunization with deiminated hFBG, all mouse strains analysed produced high amounts of anti-FBG antibodies, while relatively low levels of anti-citrulline antibodies and little or no anti-FBG antibodies crossreactive with mouse FBG (mFBG) were obtained. Mice immunized with normal hFBG also produced high amounts of anti-hFBG antibodies. However, whereas mice with MHC class II molecules similar to RA-non-susceptible HLA-DR4 alleles produced low levels of anti-hFBG antibodies with crossreactivity to mFBG, mouse strains with RA-susceptible HLA-DR4-equivalent MHC class II molecules contained high levels of such crossreactive anti-mFBG antibodies. Similar results were obtained with HLA-DR4*0401, human CD4-double-transgenic mice. However, none of the more than 600 mice investigated developed arthritis. These data indicate that the quality and/or quantity of anti-FBG autoantibodies or of anti-citrulline antibodies, produced in the studied mouse strains, are insufficient to induce arthritis.

Animals↗
PubMedDate not supplied

Sympathoadrenal and renin-angiotensin systems in the development of two-kidney, one clip renal hypertension in rats.

The relative roles of the sympathetic nervous system and renin-angiotensin system in the development of two-kidney renal hypertension were studied using four groups of rats: Group I = vehicle control; Group II = 6-OH-dopamine (2 weeks prior to renal clipping then weekly throughout the study); Group III = adrenal medullectomy plus vehicle; Group IV = 6-OH-dopamine plus adrenal medullectomy. Six weeks after clipping of a single renal artery, plasma renin activity (PRA) was comparably elevated in all groups. However, mean blood pressure (MBP) of Group II was lower than that of Group I controls (154.7 +/- 6.8 vs 197.3 +/- 6.6 mm Hg respectively). The MBP of Group III (207.0 +/- 5.2 mm Hg) was not different from that of Group I whereas in Group IV (134.2 +/- 18.0 mm Hg) it was markedly lower. All groups of rats were given a single dose of captopril (30 mg/kg p.o.) to inhibit the renin-angiotensin system. Despite differences in starting MBP, captopril caused similar reductions (38-50%) of MBP and increases in PRA in all groups. Similar results were obtained in two-kidney renal hypertensive rats with hypertension of 12 weeks' duration. It is concluded that the sympathetic nervous system does not contribute to the elevated PRA in two-kidney renal hypertensive rats but does contribute significantly to the development of hypertension in this model.

Adrenal Glands↗
PubMedDate not supplied

Effects of captopril on vascular reactivity of SHR in vivo and in vitro.

The effect of captopril treatment (100 mg/kg by mouth daily for up to 6 months) on pressor responses to norepinephrine (NE) and angiotensin II (AII) was examined in spontaneously hypertensive rats (SHR). Also, helical strips of rat aorta were removed from rats that had been similarly dosed. The aortic strips were suspended for isometric recording in modified Krebs' solution kept at 37 degrees C and bubbled with 95% O2-5% CO2. Pressor responses of both NE and AII in vivo were inhibited by captopril in SHR treated for all treatment periods. Responses to NE were more significantly and consistently inhibited than those for AII. Aortic strips from SHR previously dosed with captopril showed equivalent or greater contractile responses to potassium chloride (KCl) and NE, when compared with strips from untreated age-matched controls. In aortic strips from untreated Sprague-Dawley rats incubated with captopril, 30 micron g/ml for 1 hour ( a concentration 6000 times higher than that needed to inhibit angiotensin-covering enzyme by 50% in vitro), captopril had no effect on nitroglycerin-induced relaxation or NE-induced contractions, whereas ethacrynic acid (25 micron g/ml) reduced both the NE contractile response as well as the nitroglycerin-induced relaxation. These results suggest that captopril has no direct effect on the ability of isolated vascular smooth muscle to contract or relax despite causing a significant inhibition of pressor responses in vivo. It is suggested that this effect is related to an interaction of captopril with blood-borne elements necessary for the full expression of vasoconstriction, but unrelated to angiotensin-converting enzyme inhibition.

Angiotensin II↗
PubMedDate not supplied

Participation of the complement system in ischemia/reperfusion injury.

Reperfusion of ischemic skeletal muscle is associated with an early infiltration of WBC, a process mediated by locally generated chemotactic factors. We present evidence that selective activation of the alternative complement cascade occurs in response to skeletal muscle ischemia/reperfusion injury. Complement activation may result in the generation of peptides which are chemotactic for neutrophils, and the formation of molecular complexes which injure cell membranes.

Animals↗
PubMedDate not supplied

Compliance with primary prevention in private practice: creating a tobacco-free environment.

A sample of private orthodontic practices (n = 40) from a controlled trial for clinician-initiated tobacco-use prevention was used to test the effectiveness of preventive medicine representative (PMR) visits in creating and maintaining an anti-tobacco office environment. Clinical staff of 20 offices, randomly assigned to the experimental group, were trained by a PMR on the use of anti-tobacco materials (no-smoking signs, posters, and print materials). Twenty control-group offices did not receive any training or special treatment. Subsequently, experimental-group offices were visited by a PMR once every three months and were telephoned six weeks after each visit over a 12-month period. During visits and phone calls, PMRs prompted offices to order anti-tobacco materials. Visits served to introduce offices to new materials and to encourage their continued use. Data from direct observations and self-report measures showed significant differences between experimental and control offices for display of anti-tobacco materials at 1.5 months and 12 months (P < .001). Results suggest that PMR visits may serve as an effective method of introducing and maintaining preventive medicine procedures in clinical environments.

Community Participation↗