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Biomedical subjects

M Zembala

Publications and source records attributed to M Zembala.

At least 109 records · Page 6Linked to original sources

Functional equivalence of cryptococcal and haptene-specific T suppressor factor (TsF). I. Picryl and oxazolone-specific TsF, which inhibit transfer of contact sensitivity, also inhibit phagocytosis by a subset of macrophages.

Monoclonal and conventional cryptococcal-specific T suppressor factors (TsF) (also called TsFmp) depress phagocytosis by a subset of macrophages, while picryl- and oxazolone-specific TsF depress the passive transfer of contact sensitivity. This paper shows that these haptene-specific TsF also inhibit phagocytosis by a subset of macrophages and, using this assay, that the anti-haptene TsF resemble the anti-cryptococcal TsF in five respects: (i) the need for reexposure to specific antigen to trigger the release of TsF; (ii) genetic restriction in action; (iii) possession of an antigen-binding site; (iv) expression of I-J determinants; and (v) inactivation by reduction and alkylation. Purification of the anti-picryl TsF by sequential affinity chromatography indicates that the inhibition of phagocytosis is due to the TsF itself and not to a TsF-antigen complex. The TsF inhibits phagocytosis by a direct action as macrophages treated with TsF and exposed to antigen do not release a second factor which inhibits phagocytosis. These results and those of the accompanying paper indicate that the anti-cryptococcal and anti-haptene TsF are functionally equivalent, antigen-specific suppressor factors.

Alkylation↗

Functional equivalence of cryptococcal and haptene-specific T suppressor factor (TsF). II. Monoclonal anti-cryptococcal TsF inhibits both phagocytosis by a subset of macrophages and transfer of contact sensitivity.

Monoclonal anti-cryptococcal TsF (which inhibits phagocytosis by macrophages) and anti-picryl TsF use the same two circuits to block the transfer of contact sensitivity (CS). Both arm macrophages which then release a macrophage suppressor factor (MSF) when exposed to antigen. This MSF depresses the transfer of CS. The evidence suggests that a single molecular species of TsF (MW ca. 70 kDa), which bears an antigen-binding site and I-J determinant, is responsible for MSF production and inhibition of phagocytosis. Anti-cryptococcal TsF also arms the T acceptor cell which then releases nsTsF-1 after triggering with a specific antigen (SCPA). This nsTsF-1, which depresses the transfer of contact sensitivity, was authentic, as shown by its I-J positivity (in contrast to MSF) and its role in the production of nsTsF-2. As anti-picryl TsF also inhibits phagocytosis, it was concluded that anti-cryptococcal TsF, originally detected by the inhibition of phagocytosis, and anti-picryl TsF, originally detected by inhibition of CS, are functionally equivalent.

Animals↗

MHC class II determinants on peripheral blood monocytes from newly diagnosed IDDM patients.

The expression of MHC class II determinants (HLA-DR, HLA-DP and Ia7) on peripheral blood monocytes (OKM1+ cells) was studied in 20 children with newly diagnosed IDDM. Monocytes of 10 children with IDDM and familial predisposition showed a statistically significant increase of HLA-DR expression when compared to control group (10 healthy children). There were no significant differences concerning Ia7 expression. HLA-DP expression was similar in all studied groups.

Adolescent↗

Improved biocompatibility of extracorporeal circulation by the use of auto-oxygenation instead of artificial oxygenator in perfusion circuit.

The aim of this study was to determine the biocompatibility of an auto-oxygenation technique of cardiopulmonary bypass. Forty patients undergoing coronary bypass surgery were studied in two groups: A (auto-oxygenation, patients' lungs used in cardiopulmonary bypass) and B (conventional technique of cardiopulmonary bypass with bubble oxygenator). The platelet count decreased to -73% of initial value in group B vs only -27% in group A, P less than 0.001. Platelet aggregation to ADP decreased slightly in group A and hardly at all in group B, P less than 0.001. A transpulmonary leukocyte sequestration was greater in group B: 1.46 +/- 0.5 x 10(3)/mm3 vs only 0.34 +/- 0.2 x 10(3)/mm3 in group A, P less than 0.001. The level of C3a increased in group A from 244 +/- 46 ng/ml to 418 +/- 34 ng/ml and in group B from 268 +/- 46 ng/ml to 521 +/- 65 ng/ml, P less than 0.001, but in group A the levels were significantly less, P less than 0.001. The current study clearly confirms the superior biocompatibility of cardiopulmonary bypass with lung over oxygenator.

Biocompatible Materials↗

[Cardiogenic shock. Surgical reperfusion and myocardial revascularization].

Emergency coronary bypass for cardiogenic shock has been associated with a high operative mortality. From February 1986 through October 1989, 40 patients with acute myocardial infarction were operated. Ten pts (25%) were in shock despite intensive treatment (intra-aortic balloon pump in 4, catecholamines in 10). Seven pts. required cardiopulmonary resuscitation before operations. After operations 66% of the patients required catecholamine support and 60% were treated with intra-aortic balloon pump. There were three (30%) hospital deaths (one in the operating room due to acute cardiac failure). Follow-up (100%),(mean 26 months) revealed one late death--39 months after operations. In functional class I were 2 patients, II--one, and III--two pts. One pt is in group IV (transplant candidate). Myocardial infarction complicated by cardiogenic shock can produce a mortality rate in excess of 85%. Contemporary medical management has had little effect on mortality, hence effective surgical therapy has evolved for this lesion.

Aged↗

Synthesis and expression in E. coli of the gene for human tumor necrosis factor (h alpha TNF).

A gene coding for human tumor necrosis factor (h alpha TNF) has been assembled by ligating short oligodeoxyribonucleotides and cloning into plasmid vectors. These oligonucleotides were prepared by the modified phosphoramidite methodology using isopropoxyacetyl (IPA) as a protecting group for exoamino- functions of nucleosides. Gene was expressed in E. coli and the protein product was purified to homogeneity by ion-exchange chromatography.

Amino Acid Sequence↗

Functional characteristics of peritoneal macrophages of renal failure patients on peritoneal dialysis.

Functional activity of peritoneal macrophages of 50 patients with end-stage renal failure on intermittent peritoneal dialysis (IPD) and of 30 control subjects with normal renal function was determined. Phagocytosis of latex particles by macrophages of dialyzed patients was significantly lower as compared with the controls. Further depression of the phagocytic activity was observed during bacterial peritonitis. Macrophages from the dialyzed patients also showed nonsignificantly decreased functional expression of Fc receptors (FcR) and increased spontaneous nitro blue tetrazolium (NBT) reduction.

Adolescent↗

Major histocompatibility complex regulation of the class of the immune response: the H-2d haplotype determines poor interferon-gamma response to several antigens.

The lymph node cells of CBA (H-2k), but not BALB/c (H-2d) mice, release interferon (IFN)-gamma into the supernatant when immunized with picryl chloride epicutaneously and then exposed to antigen (haptenized cells) in vitro 4 days later. The failure in IFN-gamma production maps to the major histocompatibility complex (MHC; H-2d) in the congenic BALB/c, BALB/k and BALB/b mice. The evidence that this is an MHC regulation of the class of response to a range of antigens and not a classical Ir gene effect is (a) the difference is seen with several antigens including picryl chloride, "oxazolone" and purified protein derivative of tuberculin and (b) BALB/c mice, which fail to produce IFN-gamma, show excellent contact sensitivity to picryl chloride. It was also found that the crosses between responder and nonresponder strains (CBA x BALB/c)F1 respond to antigen on responder cell but not on nonresponder cells. This influence of MHC on the class of the immune response is a possible basis for some of the associations of MHC with disease.

Animals↗

Protective influence of pretreatment with allopurinol on myocardial function in patients undergoing coronary artery surgery.

Xanthine oxidase is responsible for the release of free oxygen radicals during myocardial reperfusion. Allopurinol was shown to be an effective inhibitor of this reaction in the laboratory experiments, but not in patients. Thirteen male patients undergoing routine coronary artery bypass graft surgery were treated with allopurinol in doses of 15 mg/kg per day for 4 days before the operation. Haemodynamic function in the early period after cardiopulmonary bypass, ECG, enzyme release and ultrastructural findings in this group were compared with those in a control group of 13 male patients matched for age distribution and stage of coronary disease. Left ventricular stroke work index was higher in the treatment group 10 min (P less than 0.001) and 15 min after termination of cardiopulmonary bypass (P less than 0.01) and also 2 h later (P less than 0.02). In the early post-operative recovery phase fewer episodes of arrhythmia were observed in this group of patients (P less than 0.001). Electron microscopy studies of the myocardium and CK and CK-MB release showed no significant differences between groups. Thus, allopurinol may have a protective effect on the human ischaemic myocardium in the early period of reperfusion.

Allopurinol↗

The role of tumor necrosis factor in the regulation of antigen presentation by human monocytes.

Human peripheral blood monocytes pretreated with human recombinant tumour necrosis factor alpha (rTNF) showed an enhanced ability to present a soluble antigen, a purified protein derivate of tuberculin, to autologous T lymphocytes as assessed by their increased proliferation in vitro. This enhancing activity was due to TNF and not impurities in TNF preparations as anti-TNF antibodies abolished this phenomenon. The rTNF-treated monocytes showed an increased expression of HLA-DR molecules and enhanced co-stimulatory activity in the murine thymocyte assay. Pretreatment of monocytes before an antigen pulse with anti-TNF mAb inhibited antigen presentation, which indicated that endogenously produced TNF was involved. These studies thus suggest that TNF acts in an autocrine fashion and enhances the ability of monocytes to present protein antigen. It is unclear at present whether this effect is due to the modification in antigen processing, expression of MHC class II molecules, or other factors (IL-1, IL-6, adhesion molecules, etc.) that are important for the induction of T cell response to a nominal antigen. The enhancement of the antigen presenting capacity of monocytes/macrophages may be the additional mechanism of pro-inflammatory activity of TNF.

Antibodies, Monoclonal↗

Monocyte-T-cell interactions in pokeweed mitogen-activated cultures.

Monocyte-T-cell interactions were studied in pokeweed mitogen (PWM)-activated cell cultures. We addressed the question of monocyte changes in PWM-stimulated cultures of T cells and monocytes and found, by flow cytometric analysis, that PWM activation led to a loss of cells with monocyte or macrophage phenotype (CD14, HLA-DR, HLA-DQ) within 48 hr of culture in the presence of T cells (CD4+ T cells), but not in cultures of pure monocytes. Chemiluminescence measurements revealed that phagocytic stimulation of monocytic superoxide release was impaired in PWM-stimulated cultures of monocytes plus T cells, but not in PWM-stimulated cultures of pure monocytes. Furthermore, PWM induced the secretion of interferon-gamma (IFN-gamma) in primary cultures of T cells supplemented with 20% of monocytes, whereas in subsequent secondary cultures of these cells PWM induced IFN-gamma only when monocytes were added. We conclude from these flow cytometric and functional analyses that monocytes are efficiently eliminated from PWM-activated T-cell/monocyte cultures by CD4+ T lymphocytes.

Antigens, Differentiation, Myelomonocytic↗

[Surgical treatment of paroxysmal ventricular tachycardia (personal observations)].

Five patients with recurrent VT/VF resistant to medical treatment were successfully treated surgically. In 3 patients excision of the altered endocardium by Harken's method (endocardial peeling) was done; in 2 of the patients it was preceded by intraoperative electrophysiological study. Two other patients were treated alternatively: a 45-year old patients with post-MI cardiomyopathy had a cardiac transplantation and a 57-year old patient with good left ventricular function an implantation of a automatic cardioverter-defibrillator (AICD). No patient had VT and/or VF during the 14-35 month follow-up. Exercise tolerance improved in all patients. Good short- and longterm results of surgical treatment show that these methods can be effective in treating patients with life-threatening arrhythmias resistant to pharmacological therapy.

Aged↗

[Personal observations with application of auto-oxygenation techniques in the surgical management of coronary disease].

There were presented operative technique and clinical results of extracorporeal circulation (ECG) with patients lungs utilization, instead of routinely applied artificial blood oxygenators. Auto-oxygenation method was applied in 12 patients with coronary artery disease treated by coronary artery bypass grafting (CABG). Operative procedure differs from the traditional one in two additional cannulations of pulmonary artery and left atrium. Two peristaltic pumps and incorporated in circulation blood reservoirs. Polystan 892910 allows for temporary substitution of cardiac function without lung disconnection. Lungs functioning during surgery do not render it difficult. Hypothermia enables to decrease respiration rate and tidal volume with no effect on physiological blood oxygenation and CO2 exhalation. Method assessment was based on results comparison with those obtained in patients treated by traditional method using bubble oxygenators-Venotherm 5,000. PO2, PCO2, platelets number and hemolysis extent were assessed before, in 10, 30, 60 min of ECG and just after it. Platelets activity and influence of the method on hemostatic disorders were evaluated based on clotting time by Ivy. Additionally hemostatic disorders were assessed by thoracic blood drainage volume calculated from the moment of protamine administration to drainage tubes withdrawal in average 18 hours after surgery. Laboratory parameters characteristically changing during ECG were also estimated. It was proved, that auto-oxygenation diminished negative effects of ECG. Increased platelets number, faster normalization of clotting time and decreased postoperative drainage were stated in the auto-oxygenation group. Postoperative drainage in this group was 260 +/- 60 ml in comparison with 800 +/- 100 ml of the control group. Authors consider that pulmonary function remaining during ECG positively affects on postoperative hemostasis. This method can be helpful in surgical management of coronary artery disease, especially in patients with primary coagulation disorders.

Coronary Artery Bypass↗

[A case of paroxysmal ventricular tachycardia surgically treated based on electrophysiological diagnosis].

There was presented a case of recurrent ventricular tachycardia in the patient after myocardial infarction. Considering uneffective pharmacotherapy and several cardiac arrests, the patient underwent guided endo-cardiotomy based on complex electrophysiological diagnostics (including intraoperative examination). Postoperative period was uncomplicated. There were no recurrences of ventricular tachycardia during 18-month follow-up.

Electrocardiography↗

Chronic granulomatous disease of childhood: gastric manifestation and response to salazosulfapyridine therapy.

The case history of a 10-year-old boy with chronic granulomatous disease (CGD) and gastric obstruction is presented. First abdominal symptoms occurred at 4 years of age when antral narrowing was detected. Due to unresponsiveness to antibiotic and steroid treatment, salazosulfapyridine therapy was initiated. Objective remission was observed within 3 months and salazosulfapyridine was withdrawn after a further 6 months of therapy. At 6 years of age clinical and radiological recurrence of gastric obstruction was observed. Salazosulfapyridine was reinstated and continued as maintenance therapy. The child has been well for more than 4 years. Salazosulfapyridine therapy can be recommended as safe conservative treatment of gastric obstruction in CGD.

Child↗

T suppressor efferent circuit which affects contact sensitivity to picryl chloride: the late-acting, second nonspecific T suppressor factor bears I-A determinants which are responsible for the I-A genetic restriction in its interaction with its target cell.

The T suppressor efferent circuit in the picryl (TNP) system, which inhibits the passive transfer of contact sensitivity, involves at least two antigen-nonspecific factors. The second nonspecific T suppressor factor (ns-2) bears I-A determinants of both the alpha and the beta chain as shown by affinity chromatography on immobilized anti-I-A monoclonal antibodies. Sequential absorption shows that the determinants of the alpha and beta chain occur on the same molecular complex. No absorption was obtained with anti-I-E antibody. There are two genetic restrictions associated with ns-2--the first is in its release from the second T suppressor efferent cell (on exposure to antigen) and the second is in its inhibitory interaction with its target cell. Both are MHC restricted and matching in I-A (but not I-E, or I-J) is sufficient. The question was asked whether the I-A of the ns-2 was directly responsible for the I-A genetic restriction in its action. F1 TsF was made in (H-2k X H-2b)F1 mice by injecting picrylated parental cells intravenously and triggering the release of ns-2 with the corresponding picrylated parental cells. Both I-Ak- and I-Ab-positive ns-2 were produced and were separated by affinity chromatography on immobilized anti-I-A monoclonal antibody. The I-A phenotype of these separated ns-2 of F1 origin determines the genetic restriction in their action; i.e., I-Ak+ ns-2 only inhibits passive transfer by H-2k cells and I-Ab+ ns-2 only acts on H-2b cells. In contrast, the I-A haplotype of the picrylated cell used to induce the Ts cell which makes ns-2 is unimportant. It was concluded that the I-A on the ns-2, and not a possible recognition site for I-A, serves as a restriction element. This finding suggests that ns-2 may act directly on the I-A-restricted T cell which mediates contact sensitivity.

Animals↗