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Biomedical subjects

A Kahan

Publications and source records attributed to A Kahan.

At least 19 recordsLinked to original sources
PubMed1992

Abnormalities of T lymphocyte subsets in Behçet's disease demonstrated with anti-CD45RA and anti-CD29 monoclonal antibodies.

We assessed T cell subpopulations using 2-color flow cytometry with phycoerythrin conjugated anti-CD45RA and anti-CD29 and fluorescein conjugated anti-CD4 and anti-CD8 monoclonal antibodies, on peripheral blood lymphocytes from 19 patients with Behçet's disease (BD) and 18 healthy control subjects. The percentage of CD4+ cells was significantly lower in patients with BD (34 +/- 2%) than in control subjects (46 +/- 3%) (p less than 0.001). Among CD4+ cells, the percentage of suppressor-inducer (CD4+CD45RA+) cells was significantly lower in patients with BD (31 +/- 4%) than in control subjects (45 +/- 2%) (p less than 0.01), while the percentages of helper-inducer (CD4+CD29+) cells were similar in patients and controls. The percentage of CD8+ cells was significantly higher in patients with BD (36 +/- 2%) than in control subjects (26 +/- 2%) (p less than 0.001) involving both CD45RA+ and CD29+ subpopulations. Within CD4+ cells, the percentage of suppressor-inducer (CD4+CD45RA+) cells was significantly decreased in patients with active BD (26 +/- 3%) compared with control subjects (45 +/- 2%) (p less than 0.001), whereas in patients with inactive BD the difference was statistically insignificant. Our results suggest that the defective suppressive function in patients with active BD may be related to the decreased suppressor-inducer subpopulation (CD4+CD45RA+).

Adult↗
PubMed1992

An antisense interferon-beta RNA abolishes repression of c-fos gene expression.

To determine the cellular functions which are modified when interferon-beta (IFN-beta) gene expression is inhibited, a plasmid allowing the constitutive expression of RNA complementary to IFN-beta mRNA was constructed and stably introduced into L929 cells. Some of the selected clones expressing this antisense IFN-beta mRNA, named L-ASI, were unable to produce IFN-beta and lost the ability to arrest in the G0 phase of the cell cycle. Indeed, the usual transrepression of the c-fos gene observed in quiescent cells was blocked in IFN-beta antisense L-ASI clones and the c-fos gene was permanently stimulated. This overexpression of c-fos was not modified in response to protein kinase C agonists such as phorbol esters, but increased in response to the adenylate cyclase activator forskolin. In addition, the ability to induce major histocompatibility class I genes following recombinant IFN-beta treatment was impaired in antisense IFN-beta L-ASI clones, suggesting an important alteration of this cell with regard to the interferon system. Unexpectedly, the tumorigenicity of the clones was significantly diminished. We postulate that IFN-beta antisense RNA blocks the repression of the c-fos gene and thus prevents the arrest of cells in the G0 phase of the cycle.

Animals↗
PubMed1991

The effect of nifedipine on myocardial perfusion and metabolism in systemic sclerosis. A positron emission tomographic study.

We assessed the effect of nifedipine on myocardial perfusion and metabolism in 9 patients with systemic sclerosis, using positron emission tomography with a perfusion tracer (potassium-38) and a metabolic tracer (18F-fluorodeoxyglucose [18FDG]). Nifedipine, 20 mg 3 times daily for 1 week, induced a significant increase in 38K myocardial uptake, a significant decrease in 18FDG myocardial uptake, and a significant increase in the myocardial 38K: 18FDG ratio. These results indicate that the increase in myocardial perfusion is associated with modifications in myocardial energy metabolism, which probably result from a beneficial anti-ischemic effect of nifedipine in patients with systemic sclerosis.

Animals↗
PubMed1991

The effect of cisapride on gastro-oesophageal dysfunction in systemic sclerosis: a controlled manometric study.

1. Cisapride is a novel prokinetic drug which facilitates or restores motility throughout the gastrointestinal tract. Its mechanism of action is thought to involve enhancement of acetylcholine release in the myenteric plexus of the gut. 2. The effect of intravenous cisapride 10 mg on gastro-oesophageal dysfunction was investigated in 20 patients with systemic sclerosis, using a double-blind, randomised, cross-over, placebo-controlled manometric study design. 3. The increase in lower oesophageal sphincter pressure was significantly higher after cisapride (mean +/- s.e. mean, 8.3 +/- 2.1 cm H2O) than after placebo (mean +/- s.e. mean. 0.1 +/- 0.3 cm H2O) (P less than 0.001). The increase in the number of fundic gastric contractions during the 30 min study period was significantly higher after cisapride (mean +/- s.e. mean, 7.7 +/- 2.3) than after placebo (mean +/- s.e. mean, 0.9 +/- 0.6) (P less than 0.01). 4. No serious clinical adverse effects were observed. 5. The study demonstrates that intravenous cisapride induces a significant increase in lower oesophageal sphincter pressure and in the number of fundic gastric contractions, which may be beneficial in the treatment of scleroderma gastro-oesophageal dysfunction. Further long-term studies of the effect of oral cisapride in patients with systemic sclerosis are warranted.

Cisapride↗
PubMed1991

Abnormalities of T lymphocyte subsets in systemic sclerosis demonstrated with anti-CD45RA and anti-CD29 monoclonal antibodies.

T cell subpopulations were assessed by two colour flow cytometry with phycoerythrin conjugated anti-CD45RA and anti-CD29 and fluorescein conjugated anti-CD4 and anti-CD8 monoclonal antibodies, on peripheral blood lymphocytes from 12 patients with systemic sclerosis and from nine control subjects. The percentage of CD4+CD29+ cells was significantly higher in patients with systemic sclerosis than in controls (mean (SEM) 68.8 (3.1) v 47.9 (4.1) respectively). CD4+CD45RA+ cells were not significantly different in patients and controls. CD8+CD29+ and CD8+CD45RA+ subpopulations were significantly higher in patients with systemic sclerosis than in controls (83.0 (3.2) v 58.7 (6.8) and 80.2 (3.0) v 66.9 (3.2) respectively). The increase in the percentage of CD29+ cells suggests an activation of memory cells in patients with systemic sclerosis, which may play an important part in the pathogenesis of the disease.

Antibodies, Monoclonal↗
PubMed1990

Handedness, immune disorders and information bias.

In order to investigate the relations between handedness and migraine or immune disorders, we performed a case control study comparing the handedness of patients suffering from systemic lupus erythematosus (SLE), type I diabetes, Graves' disease, or migraine to that of a random sample of controls from the general population. A handedness index was measured from a 10-item questionnaire. No significant difference was observed. But when the controls who denied having ever suffered from migraine or any allergic disease were set apart from those who gave at least one positive answer to the same questions, the former were found more right-handed, i.e. with a lower handedness index than the latter (P less than 0.05) and than the SLE patients (P less than 0.05). More generally, the mean observed handedness index of controls giving a positive answer to any question about their health was found repeatedly higher than that of controls giving a negative answer: this was observed for 27 of the 32 questions. These results are highly suggestive of an information bias, the subjects saying they use the right hand for each of the 10 activities considered in the questionnaire being more likely to deny having suffered from a given disease or used, more or less recently, some drug or medical service. Our conviction is that previous observations dealing with the same topic are also more easily explained by the presence of an information bias than by Geschwind's theory. The implications for the design of further epidemiologic studies are discussed.

Adult↗
PubMed1990

The effect of captopril on thallium 201 myocardial perfusion in systemic sclerosis.

In systemic sclerosis, abnormalities of myocardial perfusion are common and may be caused by a disturbance of the coronary microcirculation. We evaluated the long-term effect of captopril (75 to 150 mg per day) on thallium 201 myocardial perfusion in 12 normotensive patients with systemic sclerosis. Captopril significantly decreased the mean (+/- SD) number of segments with thallium 201 myocardial perfusion defects (6.5 +/- 1.9 at baseline and 4.4 +/- 2.7 after 1 year of treatment with captopril; p less than 0.02) and increased the mean global thallium score (9.6 +/- 1.7 at baseline and 11.4 +/- 2.1 after captopril; p less than 0.05). In a control group of eight normotensive patients with systemic sclerosis who did not receive captopril, no significant modification in thallium results occurred. Side effects with captopril included hypotension (six patients), taste disturbances (one patient), and skin rash (one patient). These side effects subsided when the dosage was reduced. These findings demonstrate that captopril improves thallium 201 myocardial perfusion in patients with systemic sclerosis and may therefore have a beneficial effect on scleroderma myocardial disease.

Adult↗
PubMed1990

Pharmacodynamic effect of nicardipine on left ventricular function in systemic sclerosis.

Left ventricular dysfunction in systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance in coronary microcirculation. We evaluated the pharmacodynamic effect of the calcium channel blocker nicardipine on left ventricular function assessed by radionuclide ventriculography in 20 patients with systemic sclerosis. Resting gated, blood-pool images were obtained at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SEM) left ventricular ejection fraction significantly increased from 65.4 +/- 2.3% at baseline to 71.3 +/- 2.3% after nicardipine (p less than 0.005). The mean global defect score significantly decreased from 2.90 +/- 0.73 without nicardipine to 1.50 +/- 0.52 with nicardipine (p less than 0.01). The mean number of left ventricular sectors with severe hypokinesis significantly decreased from 0.80 +/- 0.24 at baseline to 0.20 +/- 0.09 after nicardipine (p less than 0.05). No significant side effects were observed with nicardipine. These results demonstrate short-term improvement in left ventricular function with nicardipine in patients with systemic sclerosis.

Adult↗
PubMed1990

Pharmacodynamic without pharmacokinetic interaction between cicloprolol, a partial beta 1-adrenoceptor agonist, and digoxin in healthy subjects.

1. Cicloprolol is a partial beta 1-adrenoceptor agonist considered for the treatment of patients with coronary artery disease and impaired left ventricular function. In such patients, digoxin remains in widespread use. 2. We assessed the pharmacokinetic and pharmacodynamic interaction between oral cicloprolol 50 mg day-1 and oral digoxin 0.25 mg day-1 in 10 healthy male volunteers, using a double-blind, randomised protocol, during three 8 day periods. Digoxin was given alone during the first period to reach steady state; then digoxin was given with cicloprolol or placebo during the second and third periods, according to a cross-over design. 3. No significant adverse effects were observed. 4. The pharmacokinetics of digoxin were not different significantly at the end of the placebo-digoxin and cicloprolol-digoxin periods. 5. A significant increase in minimum heart rate and mean nocturnal heart rate, assessed by 24 h Holter recordings, was observed at the end of the cicloprolol-digoxin period as compared with the placebo-digoxin period (means +/- s.e. mean, 57.1 +/- 3.2 beats min-1 vs 52.2 +/- 3.1 beats min-1, P less than 0.01; and 65.6 +/- 3.8 beats min-1 vs 59.9 +/- 3.9 beats min-1, P less than 0.01, respectively). 6. A significant increase in left ventricular ejection fraction and shortening fraction, assessed by echocardiography, was noted at the end of the cicloprolol-digoxin period as compared with the placebo-digoxin period (means +/- s.e. mean, 66.4 +/- 1.4% vs 61.3 +/- 1.2%, P less than 0.05; and 37.0 +/- 1.1% vs 33.3 +/- 0.9%, P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Cytotoxic T cells against herpes simplex virus in Behçet's disease.

Lymphocytes from 36 patients with Behçet's disease (20 in remission and 16 in active phase) were stimulated in vitro with herpes simplex virus and then tested for their ability to generate cytotoxic T cell responses to the virus. Significant cytotoxic responses were found. CD4+ and CD8+ subpopulations from the patients in remission generated specific cytotoxic activity against autologous target cells. These observations suggested that CD4+ and CD8+ cytotoxic T cells may have an important host response in herpes virus infection in Behçet's disease.

Adolescent↗
PubMed1990

Establishing a phase I unit: organisation.

The organisation of a phase I unit must take into account the safety, quality and scientific requirements of such studies. The clinical pharmacology unit demands a highly qualified staff, as well as intensive care equipment. The investigator, generally a clinical pharmacologist who coordinates the different tasks as a project leader, has often to initiate a fruitful collaboration with a specialised consultant staff in order to implement the studies.

Drug Evaluation↗
PubMed1990

Normal suppressive T cell function of Epstein-Barr virus induced B cell activation in type 1 (insulin dependent) diabetes mellitus.

Several studies have demonstrated abnormalities of T cell regulation of Epstein-Barr virus-induced B cell activation in systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, and systemic sclerosis. However, a normal suppressive peripheral T cell function was observed in Graves' disease. To investigate whether this abnormality is a common feature to other autoimmune diseases, we studied T cell regulation of Epstein-Barr virus induced B cell activation in 15 newly diagnosed type 1 (insulin dependent) diabetes mellitus patients and 10 normal control subjects. Peripheral B lymphocytes infected with Epstein-Barr virus were cultured for 20 days in the presence or absence of autologous T cells at different ratios (1:1 and 1:4). IgM and IgG secretions into the supernatants were determined using an enzyme-linked immunosorbent assay. The extent of suppression when T cells were added, as measured by a suppression ratio, was not significantly different in type 1 (insulin dependent) diabetes mellitus patients and normal subjects. We conclude that in type 1 (insulin dependent) diabetes mellitus, the autoimmune reactivity is not dependent upon a generalized suppression defect. It can be hypothesized, therefore, that in type 1 diabetes mellitus as well as in Graves' disease, a local or organ specific suppressor deficit may induce the autoimmune phenomena.

Adolescent↗
PubMed1989

Increased proto-oncogene expression in peripheral blood T lymphocytes from patients with systemic sclerosis.

The expression of c-myc, c-myb, and c-ras proto-oncogenes, determined using RNA hybridization techniques (slot-blot), was significantly increased in peripheral blood T lymphocytes, but not in B cells, from 17 patients with systemic sclerosis with diffuse scleroderma, compared with the expression in normal control subjects. The magnitude of expression of c-myc and c-myb tended to be higher in patients with early, active disease. These results demonstrate an in vivo activation of T cells from systemic sclerosis patients, which may play an important role in the pathogenesis of the disease.

Actins↗
PubMed1989

Lyme arthritis.

Evanescent arthralgias and myalgias are common early symptoms of Lyme disease. Transient, intermittent episodes of monoarticular, oligoarticular, or sometimes migratory polyarticular arthritis, lasting weeks to months, with disease-free intervals, are frequently observed in untreated patients with erythema chronicum migrans. A minority of patients develop chronic joint involvement, most commonly affecting the knee. Antibiotic therapy given during erythema chronicum migrans is often protective with regard to late joint manifestations. In chronic Lyme arthritis, however, the response to antibiotics is variable.

Anti-Bacterial Agents↗
PubMed1989

Lacrimal and salivary immunoglobulins in Sjögren's syndrome.

The diagnosis of Sjögren's syndrome is sometimes difficult. We have previously demonstrated the diagnostic value of salivary immunoglobulins IgG and IgM in Sjögren's syndrome. In the present study, we assessed both lacrimal immunoglobulins (1 Ig) and salivary Ig (s Ig) in Sjögren's syndrome. We studied 112 patients: 71 had rheumatoid arthritis (57 sero positive), 19 had connective tissue diseases or vasculitis (six Sjögren's syndrome alone, six systemic sclerosis, three mixed connective tissue diseases, three polyarteritis, one relapsing polychondritis), and 22 patients had other inflammatory, metabolic or degenerative joint diseases. Lacrimal Ig and salivary Ig were assessed by double immunodiffusion with antisera specific for IgG, IgM and IgA. Each Ig class was scored on a scale ranging from 0 to 3 plus without knowledge of the patient's diagnosis. The results of factorial analysis demonstrated a strong relationship between xerophtalmia, positive Schirmer's test, s IgG, s IgM, 1 IgG, and 1 IgM in patients with seropositive rheumatoid arthritis or other connective tissue diseases. Analysis of individual parameters showed a significant relationship between 1 IgG and ocular complaints (P less than 0.01), positive Schirmer's test (P less than 0.05), positive rose bengal dye test (P less than 0.05), 1 IgM (P less than 0.01), s IgG (P less than 0.01) and s IgM (P less than 0.05). A significant relationship was also found between s IgG and ocular complaints (P less than 0.02), positive rose bengal dye test (P less than 0.01), positive minor salivary gland biopsy (P less than 0.05), s IgM (P less than 0.01), and 1 IgM (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗