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Biomedical subjects

T Haim

Publications and source records attributed to T Haim.

At least 19 recordsLinked to original sources
PubMed2001

Nitric oxide and cGMP protein kinase activity in aged ventricular myocytes.

We tested the hypothesis that nitric oxide-induced negative functional effects through cGMP would be reduced in aged cardiac myocytes. Maximum rate of shortening (R(max)) and percent shortening of ventricular myocytes from young (6 mo) and old (3 y) rabbits were studied using a video edge detector. cGMP-dependent phosphorylation was examined by electrophoresis and autoradiography. Myocytes received a nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP, 10(-7), 10(-6), and 10(-5) M) followed by KT-5823 (10(-6) M), a cGMP protein kinase inhibitor. Baseline function was similar in young and old myocytes (89.1 +/- 4.5 young vs. 86.4 +/- 8.3 microm/s old R(max), 5.6 +/- 0.3 vs. 5.2 +/- 0.7%shortening). SNAP (10(-5) M) decreased R(max) in both young (25%, n = 6) and old myocytes (24%, n = 7). SNAP also reduced percent shortening by 28% in young and 23% in old myocytes. The negative effects of SNAP were partially reversed by KT-5823 only in young myocytes. Multiple proteins were phosphorylated by cGMP, and KT-5823 could reduce this effect. The degree of phosphorylation was significantly less in old myocytes. These results suggest that the functional response of ventricular myocytes to nitric oxide was preserved during aging. However, the importance of cGMP-dependent protein phosphorylation was decreased, indicating a shift to other pathways.

Aging↗
PubMed1999

Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthritis.

OBJECTIVES: To evaluate in various groups of patients with chronic joint disease the sensitivity and specificity of anti-Sa antibody, recently described in sera from adults with rheumatoid arthritis (RA); and to determine the prognostic significance of anti-Sa in initial sera from patients with long standing RA with or without severe joint destruction. METHODS: Serum samples from 489 patients were included. Of these, 154 were collected from patients with RA attending 2 rheumatology units. Controls were 335 patients with a variety of inflammatory joint diseases other than RA. IgG anti-Sa was detected using an immunoblotting method with purified Sa antigen from human placenta extracts. All patients were tested for the following antibodies: rheumatoid factor (RF), anti-keratin antibody (AKA), antiperinuclear factor (APF), and anti-RA 33. HLA class II DRB alleles were also determined. RESULTS: Anti-Sa was detected in 39.8% of RA sera overall, 46.7% of sera from the long standing RA group, and 23.5% of sera from the recent onset RA group (p<0.01). In patients with long standing RA, statistically significant associations were found between the presence of anti-Sa and the following variables: RF (p<0.0001), AKA (p<0.0001), APF (p<0.00001), and HLA DRB1*04 or 01 (p<0.01). In contrast, no association was found with anti-RA33. Anti-Sa was positive in 11 adult controls (7.8%) and in 26 pediatric patients with juvenile chronic arthritis (22%). The specificity of anti-Sa for RA was 92.1% in adults with well characterized rheumatic diseases and 85.9% in adults and children together. Among patients with long standing RA, those with destructive disease were more likely to test positive for anti-Sa (66.6%) than those with nondestructive disease (22.2%) (p<0.0001). Comparisons with other serologic markers for RA demonstrated that anti-Sa was sensitive (68.4%) and was also the test with the highest specificity (79%), positive predictive value (75%), and negative predictive value (71%) for discriminating between patients who do and those that do not develop late severe radiographic damage. CONCLUSION: Immunoblot-detected IgG anti-Sa is a sensitive serologic marker for RA patients with severe radiographic damage.

Adult↗
PubMed1998

The NMDA (N-methyl-D-aspartate) receptor antagonist memantine in the treatment of postherpetic neuralgia: a double-blind, placebo-controlled study.

A double-blind, randomized, placebo-controlled trial was conducted to study the analgesic efficacy of the NMDA (N-methyl-D-aspartate) receptor antagonist memantine (1-amino-3,5-dimethyladamantane hydrochloride) in relieving postherpetic neuralgia (PHN). Memantine (or an identical-looking placebon=12/group) was administered at a dose of 10 mg/day for one week, and 20 mg/day for an additional 4 weeks. All patients were required to record their pain level twice daily during the entire study period, with the use of a 0-10 numerical pain scale (NPS). The McGill Pain Questionnaire (MPQ), spontaneous pain, and a series of mechanical and thermal stimuli-induced pain were measured with the use of a 0-100 visual analogue scale (VAS), on six office visits. Quantitative thermal testing (QTT) and routine blood tests were performed at the beginning and at the end of the study. Although reduction in spontaneous pain, mechanical and cold allodynia, mechanical hyperalgesia, and < > like pain were found in both groups, there were no significant differences between memantine and the placebo on any of the outcome measures. No changes were found in either group in MPQ scores or in quantitative thermal thresholds. Although three patients were withdrawn from the memantine group and only one from the control group, no differences in incidence of adverse effects between the two groups were found. Study results show that memantine is ineffective in reducing spontaneous and evoked pain in patients with PHN. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed1998

Clinical usefulness of antibodies to U1snRNP proteins in mixed connective tissue disease and systemic lupus erythematosus.

OBJECTIVES: To determine whether the anti-68 kDaU1snRNP antibody is associated with mixed connective tissue disease and not with SLE; to evaluate correlations between anti-U1snRNP titers and disease activity; and to look for associations between anti-U1snRNP specificities and specific clinical features. PATIENTS AND METHODS: 40 patients with a positive double diffusion test for anti-68 kDa U1snRNP were studied, including 21 with mixed connective tissue disease, 14 with systemic lupus erythematosus and five with other connective tissue diseases. IgGs to 68 kDa U1snRNP were assayed using an ELISA. Clinical features, disease activity and antibody test findings were evaluated longitudinally in nine patients. RESULTS: Both proportions of patients with anti-68 kDa U1snRNP and titers of IgG to 68 kDa U1snRNP were similar in the mixed connective tissue disease and systemic lupus erythematosus groups. Patients with mixed connective tissue disease were significantly more likely to have anti-A U1snRNP or anti-C U1snRNP than those with systemic lupus erythematosus (P < 0.03 and P < 0.04, respectively). No significant correlations were found between any of the features of mixed connective tissue disease (e.g., Raynaud's phenomenon, myositis, or sausage digits) and a specific anti-U1snRNP antibody. During follow-up (mean, seven years; range, 1-25 years), changes occurred in the anti-U1snRNP profile and in the anti-68 kDa U1snRNP titer. These changes were not correlated with disease activity. CONCLUSIONS: IgGs to 68 kDa U1snRNP are not associated with a specific pattern of anti-RNP-positive connective tissue disease. No useful information can be gained by monitoring anti-68 kDa U1snRNP IgG titers over time. A Western blot profile including anti-A U1snRNP or anti-C U1snRNP indicates a high likelihood of U1snRNP-associated mixed connective tissue syndrome (MCTD).

Adolescent↗
PubMed1997

Anticentromere antibodies in rheumatologic practice are not consistently associated with scleroderma.

Anticentromere antibodies identified by indirect immunofluorescence are a valuable aid to the diagnosis and prognosis of patients with systemic sclerosis since they are associated in 50% to 80% of cases with limited cutaneous systemic sclerosis, a pattern usually associated with a good prognosis. We studied clinical presentations in rheumatology patients with anticentromere antibodies by indirect immunofluoresence and by ELISA and/or Western blot, but without scleroderma or Raynaud's phenomenon. Eight of 34 (23.5%) rheumatology clinic patients with centromere antibodies met these criteria, seven women and one man, with a median symptom duration of six years (range 1-20 years). Four had Sjögren's syndrome, one had isolated xerostomia, one systemic lupus erythematosus, one seronegative symmetric polyarthritis and one primary biliary cirrhosis with arthralgia. The mean anticentromere antibody titer in these eight patients was similar to that in the patients who had at least Raynaud's phenomenon. Given the low incidence of scleroderma, these data illustrate the poor predictive value of anticentromere antibodies for the diagnosis of scleroderma in rheumatology clinic patients.

Adult↗
PubMed1996

Antineutrophil cytoplasmic antibodies in rheumatoid arthritis patients.

We determined the occurrence of antineutrophil cytoplasmic antibodies (ANCAs) and their specificities in 77 rheumatoid arthritis (RA) patients and compared them with 25 patients with psoriatic arthritis (Pso), 19 with drug-induced lupus erythematosus (DI-LE) and 11 with systemic lupus erythematosus (SLE). Thirty-two percent of RA patients had positive indirect immunofluorescence (IIF) stains (P or atypical ANCA). Twenty-nine per cent of patients with rheumatoid vasculitis (RAV), 48% with long-standing RA (LSRA) and 20% with early RA (Ely RA) had positive ANCAs compared with 4% of Pso patients, 47% of DI-LE patients and 45% of SLE patients. Western blotting (with polymorphonuclear cell extracts or alpha-granules) and alpha-granule enzyme-linked immunosorbent assay (ELISA) yielded variable results and proved unhelpful for characterizing the specificities of ANCAs. ELISAs based on commercial purified lactoferrin (LF), myeloperoxidase (MPO), human elastase (HLE) and cathepsin G (CG) showed that anti-HLE antibody was the most prevalent (14%) antibody in RA, followed by anti-MPO antibody and anti-LF antibody (10% each). Statistical analysis of antibody prevalence by clinical presentation showed that LSRA patients were more likely to have anti-HLE antibody and that DI-LE patients were more likely to have anti-CG antibody compared with the other patient groups. In lupus patients serial ELISA titration of ANCAs (LF and MPO) was found to be reliable for predicting the outcome. The overall incidence of ANCAs in RA patients was 33% by IIF.

Antibodies, Anti-Idiotypic↗
PubMed1995

Anti-vascular endothelial cell antibodies (AECA): comparison of two assay methods and clinical applications.

Vascular endothelial cells may be a target for autoantibodies (AECAs) against membrane antigens that are constitutively expressed, induced or bound to their surface. To test this hypothesis, we used an enzyme-linked immunosorbent assay (ELISA) with two types of human endothelial cells as the substrate, i.e., human umbilical cord vein endothelial cells (HUVECs) or the hybrid cell line EAhy-926 obtained by fusion of HUVECs with the bronchial carcinoma cell line A549. A comparative functional study of these two cell types demonstrated that EAhy-926 cells produced only small amounts of VIII von Willebrand factor and tissular factor, did not contain Weibel Palade bodies visible under the electron microscope, and expressed ICAM-1 and selectin E in levels of no more than 15% of those expressed by human umbilical cord vein endothelial cells both after stimulation by bacterial lipopolysaccharide and under basal conditions. However, the two assay methods yielded similar IgG AECA titers when used on sera from patients with rheumatoid vasculitis or antiphospholipid syndrome. These antibodies did not exhibit cytotoxicity for cord vein or EAhy-926 cells. They were not specific for endothelium, since their activity decreased by a mean of 40% after incubation of sera with the epithelial cell line A549. A cross-sectional study of 565 sera demonstrated that anti-vascular IgG and IgM AECAs reactive with EAhy-926 cells occurred mainly in patients with dermatomyositis (IgG, 58%; IgM, 22%), systemic scleroderma (IgG, 48%; IgM, 18%), primary Sjögren's syndrome (IgG, 44%; IgM, 12%) and secondary and primary systemic vasculitides (IgG, 38%; IgM, 18%) including Wegener's granulomatosis. A longitudinal study in patients with Wegener's granulomatosis showed that AECAS were predictive of disease activity.

Antibodies↗
PubMed1991

[Detection of anti-Ro(SS-A) by using immunoimprint. Comparison with double diffusion in agar. Apropos of a series of 63 primary Gougerot-Sjögren syndromes].

Among soluble anti-nuclear antigen auto-antibodies, anti-Ro(SS-A) were, for unknown reasons, difficult to detect by immunoimprint (II). The aim of this study was the development of a method of preparation of Ro(SS-A) antigen enabling greater sensitivity in the detection by II of the corresponding antibodies, then application of this method in a series of 63 cases of primary Sjögren's syndrome in order to study the clinical significance of anti-Ro(SS-A) antibodies. Ro(SS-A) antigen was prepared from human spleen and partially purified on DE-52 resin. The protein extract prepared reacted in II with reference anti-Ro(SS-A) and anti-La(SS-B) antibodies. The series of 63 cases of primary Sjögren's syndrome (57 F, 6M) included 50 of extraglandular primary Sjögren's syndrome and 13 of isolated glandular primary Sjögren's syndrome. Twenty two cases of primary Sjögren's syndrome had anti-Ro(SS-A) (35%). Twenty patients had anti-Ro(SS-A) by II (32%) and 17 by double diffusion in agar (27%) (p = NS). Among 7 discordant sera, 2 were not detected by II. The incidence of anti-Ro did not differ statistically between the extraglandular (40%) and glandular (15%) primary Sjögren's syndrome groups. Patients were divided into two groups according to whether they did (n = 22) or did not (n = 41) produce anti-Ro(SS-A).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antinuclear↗
PubMed1990

[Profile of antinuclear antibodies in 14 cases of extinct systemic lupus erythematosus for more than 3 years].

In order to study the profile of antinuclear antibodies (ANA) and anticytoplasm in the clinical recovery period, we searched for ANA by 4 methods (indirect immunofluorescence on HEp-2 and Crithidia luciliae cells, double diffusion in agar against veal thymus and human spleen, immunoprint with a total extract of HeLa cells) in 14 patients with SLE extinct since more than 3 years. The population under study consisted of 12 women and 2 men, aged 43 years on average at the time of study (extremes: 28-64 years). The average lapse of time between the diagnosis of SLE and date of sampling is of 12.6 years (extremes: 3-22 years). The average remission/clinical recovery time during the study is of 8.9 years (extremes: 3-22 years). Seven patients were administered mild corticotherapy (average dose of prednisone: 4.7 mg/day). All the sera preserved ANA or anticytoplasm, distributed in the following way: presence of antinucleus: 10/14 (71.5%); average titre 40; speckled aspect: 10/10; presence of anti-DNA: 0/14; presence of anti-ECT: 2/14 (14.3%): anti-SSB 1 case, anti-RNP 1 case; positive immunoprint: 12/14 (85.7%): anti-Sm 5 cases (isolated or associated), isolated anti-SSB 2 cases; isolated anti-Ro 2 cases; various unidentified 3 cases. These results suggest that the production of ANA and anticytoplasm other than anti-DNA continues during the period of clinical extinction of SLE, underlining the rarity of a complete biological recovery and the necessity of long term clinical surveillance.

Adult↗
PubMed1989

Anti-Scl-70 antibodies detected by immunoblotting in progressive systemic sclerosis: specificity and clinical correlations.

One hundred and forty five serum samples from patients with a connective tissue disease and 30 serum samples from healthy blood donors were analysed by immunoblotting. The presence of anti-Scl-70, which seems to discriminate between progressive systemic sclerosis (PSS) and the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome, was found in 31/64 (48%) patients with PSS, in 6/55 (11%) patients with systemic lupus erythematosus, in 2/26 (8%) patients with mixed connective tissue disease, and in none of 30 healthy blood donors. These data resulted in a specificity of 93% for this antibody in systemic sclerosis. For patients with PSS the duration of disease was significantly shorter in those with anti-Scl-70 antibodies than in those without, whereas the presence of anti-Scl-70 did not correlate with severity of disease. An 82% prevalence of anticentromere antibodies in patients with the CREST variant compared with a 4% prevalence in patients with PSS or with overlap syndrome confirms the high diagnostic value of this autoantibody for the CREST variant of PSS.

Aged↗
PubMed1989

Immunoblotting profiles in 55 systemic lupus erythematosus sera lacking precipitating antibodies to extractable nuclear antigens.

Serum samples from 55 patients with systemic lupus erythematosus (SLE) were selected for the absence of anti-extractable nuclear antigen antibodies after routine immunodiffusion tests. These sera were immunoblotted for anti-Sm and anti-RNP antibodies on a HeLa cell nuclear extract. Ten (18%) were negative and 45 (82%) produced complex patterns: 10 (18%) suggestive of anti-Sm, three (5%) anti-RNP, and 32 (58%) a combination of anti-Sm and anti-RNP antibodies. These data were very similar to those obtained from sera from a control group of 28 SLE sera selected for positivity of anti-Sm and anti-RNP precipitins with the immunodiffusion test. IgM isotype antibodies to the D peptide were significantly more prevalent than IgG isotype antibodies, whereas antibodies to the 68 kD polypeptide were of both IgM and IgG isotypes. Sera with an anti-Sm/RNP immunoblotting pattern stemmed from a group of patients with SLE with a higher titre of anti-dsDNA antibodies. Among clinical symptoms, the incidence of haemolytic anaemia was higher in the group of patients with the anti-Sm immunoblotting profile. Patients with an anti-RNP immunoblotting profile showed a higher incidence of cutaneous symptoms. It is concluded that immunoblotting for anti-Sm or anti-RNP antibody determination is a very sensitive diagnostic tool in patients with SLE.

Adult↗
PubMed1989

[Antinuclear and anticytoplasmic antibodies in 24 cases of dermatomyositis. Value of western blotting].

Antinuclear and anticytoplasmic antibodies were detected, using 4 methods, in 96% of the sera (23/24) from 24 dermato- or polymyositis patients, who were followed in the Rheumatology Department. Immunofluorescent (IF) labeling of Hep-2 cell smears was more sensitive than IF staining of liver sections (72 vs 67%), and the patterns observed were in agreement 20/24 times. Gelose precipitation is even less sensitive (29%), but enables a characterization of the antigens recognized: 3 anti-RNP, 3 anti-J01, 1 anti-PMScl, 1 anti-SSB and 1 anti-Ro; the latter two specificities were associated with a sicca syndrome. Western-blotting was the most informative method because it was highly sensitive (79%) and identified the principle antigen-antibody systems: anti-U1-RNP (33%) and anti-Scl70 (33%), both associated with myositis with an overlap syndrome (p less than 0.02); anti-J01 (25%) associated with various forms of myositis; and, more rarely, anti-SSB and anti-Ro (both 4%) when a sicca syndrome was present. Finally, non-identified specificities were observed in 37% of the cases.

Adolescent↗