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Biomedical subjects

A Vazquez

Publications and source records attributed to A Vazquez.

At least 109 records · Page 6Linked to original sources

[Activation of human B lymphocytes by a particulate antigen].

A specific IgM antibody response toward the trinitrophenol (TNP) hapten can be induced in mononuclear blood cell suspensions upon culture with a particulate antigen: polyacrylamide beads conjugated with the TNP hapten (TNP-PAA). The response, and its specificity, are demonstrated by an increase in the number of TNP binding B lymphocytes (specific rosette forming cells), by the appearance of cells producing anti-TNP antibody at a high rate (haemolytic plaques), (ELISA test). The anti-TNP response requires monocytes, the role of which is to produce interleukin-1 (IL-1) and T lymphocytes (belonging to the T4 helper subset) the role of which is to produce interleukins (the characterization of which is under study). We propose a model or B cell activation based on the following signals: an early specific signal, provided by the particulate antigen; several non specific signals, provided by T derived interleukins. The anti-TNP response is negatively regulated by monocytes, the functional states of which can be modified in certain situations (autoimmunity, aging) or influenced by glucocorticoids. Suppressor T lymphocytes of this response (not exclusively of the T8 phenotype) can be induced and this can allow the evaluation of T suppressor cell function. This was used in adult idiopathic thrombocytopenic purpura treated with high doses of intra-venous gammaglobulins.

Acrylic Resins↗

Molsidomine--an effective antianginal drug. Results of an acute randomized stress-testing study.

The antianginal efficacy of molsidomine (single oral dose of 2 mg), a new antianginal drug, was evaluated in 12 patients with coronary artery disease in a double-blind randomized placebo-controlled study by bicycle ergometry. Besides the standard ergometric parameters, the myocardial efficiency index (MEI) was determined from the ratio of the maximum workload (kgm/min) to double product (mm Hg X min) X 10(-2), normalized for body surface area. Compared to placebo, molsidomine decreased positive exercise tests by 50%, pain response by 66%, and the magnitude of ST depression by 43%. Furthermore, the onset of ergometric positive response was delayed, with an increase in maximum workload achieved (+21%), total work performed (+43%), and duration of exercise (+28%). MEI also increased from 0.98 +/- 0.43 to 1.18 +/- 0.44 (p less than 0.005), due to a significant increase in maximal workload without a parallel increase in double product. These findings suggest that molsidomine is an effective antianginal drug and improves myocardial efficiency in patients with angina due to coronary artery disease.

Aged↗

Functional properties of two human B cell growth factor species separated by lectin affinity column.

The supernatants from PHA-activated normal human T cells (conditioned medium) were fractionated by differential adsorption on Con A-Sepharose columns. The effluent contained both IL 2 activity (tested on the CTL-L2 cell line) and BCGF activity (tested on anti-mu-activated normal B-enriched cells). Absorption of such effluent on PHA-activated T cell blasts removed the IL 2 activity without affecting the BCGF activity. The eluate also displayed BCGF activity (tested on anti-mu-activated B-enriched cells) without detectable IL 2 activity. The two BCGF species isolated by this criteria synergize with semipurified IL 1 to support the anti-mu-induced proliferation of highly monocyte-depleted B cells. Both BCGF species required the presence of anti-mu Ab to support the proliferation of small B cells (at the G0 stage). However, in contrast to crude conditioned medium and to the BCGF present in the effluent, the BCGF present in the eluate was unable to induce the proliferation of unfractionated or large (at the G1 stage) B cells in the absence of anti-mu Ab. These results support the existence of two functionally different human BCGF species, differing at least in their relative sugar content and distinct from IL 2.

Adsorption↗

Helper T cell activation for the human B cell response to trinitrophenylated polyacrylamide beads: involvement of the T4 antigen.

The monoclonal antibody (mAb) OKT4A (but not OKT4) inhibits the in vitro antibody response of human peripheral blood mononuclear cells. The target of OKT4A mAb is the helper T cell, as the helper cells for the antibody response to trinitrophenylated polyacrylamide beads (TNP-PAA) are exclusively in the T4 subset. The OKT4A mAb is still suppressive when the anti-TNP response of cultures of monocyte-depleted cells is supported by purified interleukin 1. Both the OKT4A mAb and anti-DR mAb suppress the non-specific T cell proliferation in the cultures leading to the in vitro mAb response. A parallel inhibition is observed for the autologous mixed lymphocyte reaction, the nonspecific B cell response, but the T cell response to mitogens is not affected. These results suggest that the recognition of self major histocompatibility complex class II determinants by the T4 molecule plays a major role in the activation of T helper cells for antibody production to this particulate antigen.

Acrylic Resins↗

Haemodynamic effects of oral molsidomine in pump failure complicating myocardial infarction.

Haemodynamic monitoring, using a Swan-Ganz balloon catheter, was done in 14 patients with pump failure associated with acute myocardial infarction, before and for 8 h after single 6 mg oral dose of molsidomine. The following changes effects were found: HR fell by 1.6 to 4.7% (significant at 4th hour; p less than 0.05); SBP was 8.4% lower after 1 h (p less than 0.05); PCP was decreased by approximately 30%, a significant effect that lasted for 8 hours (p less than 0.002). CI did not change significantly, although individual analysis showed it to have increased in 6 out of 12 cases. Stroke volume index was increased by about 6% (significant after 1 h, p less than 0.025). The left ventricular stroke work index also increased from 9.8 to 24.5% (significant after 1 and 4 h, p less than 0.01 and 0.025). These findings show the beneficial haemodynamic effects of molsidomine in pump failure complicating acute myocardial infarction.

Aged↗

Interleukin 1 can replace monocytes for the specific human B-cell response to a particulate antigen.

It is shown that the anti-trinitrophenyl (TNP) response of human B cells to trinitrophenyl polyacrylamide beads (TNP-PAA) is monocyte dependent. This response is abolished by extensive adherent cell depletion and restored by the addition of monocytes. The optimal response is obtained with 3% monocytes, higher numbers being suppressive. Supernatants from muramyl dipeptide (MDP)-activated monocytes can restore the response of monocyte-depleted preparations even when cells are cultured at suboptimal concentration. A partially purified preparation of interleukin (IL-1) has a comparable restorative ability. The following arguments suggest that monocytes do not function as antigen-presenting cells for this particulate antigen: (i) antigen-pulsed monocytes induce neither an anti-TNP response nor a specific T-cell proliferative response; (ii) allogeneic monocytes function as well as autologous monocytes to restore the response of nonadherent cells; (iii) HLA-DR-negative cells from the human leukemia cell line K562 can replace monocytes for this response. Monocyte supernatants do not replace T cells for the response of B-enriched lymphocytes, showing that T cells are directly involved in B-cell activation.

Acrylic Resins↗

Penbutolol and molsidomine synergism in angina pectoris. A double blind ergometric trial.

In order to test the additional efficacy of the combination of a beta blocker (penbutolol 40 mg single dose) with molsidomine (2 mg single dose), a double blind cross-over trial was performed in 30 patients with stable angina pectoris. Stress tests were done before and 1 h after the beta blocker alone and the combination therapy. Some training effect could be detected on comparing results from the first and second days. Combined therapy showed a better response of resting systolic arterial pressure, resting and maximal diastolic pressure, heart rate gain (from rest to maximal effort) and particularly in the angina severity score. All of these variables changed significantly in comparison to the beta blocker alone, 46 out of 60 post-drug ergometric studies were negative; of the 14 positive tests, 11 followed the beta blocker and only 3 the combined therapy. The combination of a preload reducer molsidomine and a beta blocker may be adequate for patients only partially compensated or with cardiomegaly and/or a depressed ejection fraction.

Aged↗

Effects of laser irradiation on human thrombus: demonstration of a linear dissolution-dose relation between clot length and energy density.

Because vascular thrombosis often accompanies arteriosclerotic disease in occluding blood vessels, the dissolution properties of laser irradiation were investigated and the energies needed to penetrate different lengths of thrombus were quantitated. Spectrophotometric studies show that the blood clot due to the presence of hemoglobin is well absorbed by argon laser energies, which emit blue-green wavelengths between 454 and 514 nm. Thus, laser energies transmitted directly from an argon-ion source produced vaporization and penetration of human thrombus in a linear dose-response fashion; the longer the thrombus, the greater the power intensity or time exposure necessary to penetrate the clot.

Dose-Response Relationship, Radiation↗

An overall review on prenylamine mechanisms of action in experimental models of myocardial damage.

In this review we present the effects of a well-known antianginal drug, prenylamine (PNL), in experimental models of acute myocardial damage induced by a beta-agonistic drug, isoproterenol (ISP), in several trials conducted in our laboratory in both rats (n = 204) and monkeys (n = 26). PNL significantly inhibited ISP-induced lesions, protecting the majority of animals studied. Studies dealing with the site of action of the drug, such as 45Ca, 3H-PNL and 3H-ISP trials, showed a clear membrane effect slowing down Ca transport. Correlation between ECG (inhibition of ST depression after ISP) and pathological findings in monkeys was also obtained in one of our experiments. These series of assays were useful in obtaining a more complete idea of activity and site of action of the drug. It seems that, in acute models, PNL acts as a calcium antagonistic drug rather than an adrenergic moderator.

Angina Pectoris↗

Normal and pathological electrocardiographic patterns in the Cebus monkey.

The normal electrocardiographic (ECG) pattern was determined for Cebus monkeys and compared with those obtained in animals subjected to experimental heart damage. ECG patterns were related to the anatomopathological findings in both normal and treated animals. The anatomic study revealed a vertical heart in which both ventricles constituted the frontal aspect. The experimental heart injury either through the inoculation of Trypanosoma cruzi or after the treatment with isoproterenol induced ECG changes which were correlated with specific anatomopathological lesions.

Animals↗

Randomised trial of pentoxifylline versus acetylsalicylic acid plus dipyridamole in preventing transient ischaemic attacks.

In a multicentre trial to compare the ability of a combination of acetylsalicylic acid and dipyridamole (1050 mg + 150 mg/day, group A) to prevent recurrence of transient ischaemic attacks (TIA) with that of pentoxifylline (1200 mg/day, group B), 36 patients received the combination and 30 pentoxifylline. There was no statistically significant difference between the groups as regards age, sex, blood pressure, site of origin of TIA, and incidence of other risk factors. The incidence of recurrent TIAs during 1 year of follow-up was 28% in group A and 10% in group B; this difference was significant (p less than 0.05). The incidence of permanent strokes was similar in the two groups but distinctly lower (4.5%) than that usually reported after untreated TIA.

Aspirin↗

A randomized clinical trial of pentoxifylline and antiaggregants in recent transient ischemic attacks (TIA). A one year follow-up.

A multicenter comparative trial was conducted in patients with transient ischemic attacks (TIA) to study the preventive capacity of a combination of acetylsalicylic acid and dipyridamol (1,050 mg + 150 mg/day - group A) and of pentoxifylline (1,200 mg/day - group P) in the reduction of morbidity rates. Sixty-six patients, 36 on A and 30 on P, were evaluated. There was no statistically significant difference between both groups as regards age, sex, blood pressure, localisation of TIA and incidence of risk factors. Incidence of new ischemic events during a one year follow up period in the A-group was 28% compared to 10% in the P-group, this difference being statistically significant in favour of P (p less than 0.05). Stroke incidence was similar in both groups but distinctly lower (4.5%) than the natural frequency in TIA.

Adult↗

Separate cytotoxic T lymphocyte subsets recognize the different H-2 specificities.

Using a monolayer adsorption technique, the fine specificity of cytotoxic effector T lymphocytes (CTL) generated against allogeneic or semi-allogeneic H-2 haplotypes was investigated. The results show that: (a) CTL reacting with the private specificity expressed on an H-2.K molecule can be separated from those reacting with the public specificities expressed on the same molecule and (b) the CTL that recognize cross-reacting H-2 determinants (public specificities) can also be separated into several subpopulations. These data support the hypothesis that an allogeneic stimulation induces a large number of independent T cell clones that react with H-2 determinants.

Animals↗

Double-blind controlled trial of molsidomine in hypertension.

Molsidomine (M), a new long-lasting antianginal compound, was studied in 38 hypertensive patients to assess its antihypertensive properties. Six patients were selected for an acute, single dose comparative trial with placebo over 8 h after treatment. The remaining 32 patients were used in a 1 month trial to study the effect on BP of more prolonged treatment. Systolic, diastolic and mean BP were significantly reduced after a single dose of M 4 mg, and the effect lasted for about 8 h. M also inhibited the hypertensive response to isometric exercise in handgrip tests performed 1 and 8 h after M ingestion. A dose-related decrease in systolic and diastolic BP in the one month trial was also observed. In addition to its antianginal properties, M appears to possess an interesting effect on BP in mildly to moderately hypertensive patients. A fall in BP is also a valuable effect in coronary patients with augmented metabolic demands of the heart.

Antihypertensive Agents↗

Public H-2 specificities are target determinants for alloreactive cytotoxic T lymphocytes.

The specificity of the cross-killing exerted by cytotoxic T lymphocytes (CTL's) generated against H-2 region products was investigated in a 51Cr release assay on a panel of target cells from a number of different H-2 haplotypes. Their pattern of reaction shows that: (1) The target cells, expressing public specificities (H-2.28, H-2.1, H-2.3 or H-2.8) which should, theoretically, be recognized by the CTL's were killed, while those expressing no public specificities, recognized according to the H-2 chart by the CTL's were not killed. (2) The CTL's generated against the H-2.28 specificity expressed on the D region products cross react with target cells expressing this specificity in their K region products and vice versa. The same phenomenon was observed with the H-2.1 specificity. These results provide evidence that public specificities are targets for CTL's. Antiserum reacting against the public specificity recognized by the CTL's was found to block the cross-killing, however, to the same extent as antisera directed against any specificity (private or public) expressed on the same molecule as the target determinant. Finally both the inhibition studies using anti-H-2 antisera and the direct cytotoxic assays showed that the public specificities of the H-2.28 family carried by the H-2.D and H-2.L molecules were recognized by different subpopulations of CTL's.

Animals↗