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Biomedical subjects

E Pohanka

Publications and source records attributed to E Pohanka.

At least 37 records · Page 2Linked to original sources
PubMed1996

Gastric mucormycosis due to Rhizopus oryzae in a renal transplant recipient.

Gastric mucormycosis is a rare disease with a reported fatal outcome of 98%. Manifestations range from colonization of peptic ulcers to infiltrative disease with vascular invasion and dissemination. In our renal transplant patient a deep gastric ulceration infected with Rhizopus oryzae (class Zygomycetes), which is known to be an agent of mucormycosis, was diagnosed in the early posttransplant period after antirejection therapy. The infection was successfully managed with amphotericin B and omeprazole.

Adult↗
PubMed1994

Specific down-regulation of proliferative T cell alloresponsiveness by interference with CD2/LFA-3 and LFA-1/ICAM-1 in vitro.

T cell activation requires Ag contact with the TCR in the presence of costimulatory signals provided by APCs. When Ag is presented without costimulation, T cells are functionally inactivated. Here we demonstrate that interference with distinct adhesion molecules during Ag contact using mAbs leads to Ag-specific functional inactivation of alloreactive T cells. We found that the presence of a mixture of mAbs specific for CD2, LFA-3, LFA-1 alpha- and beta-chain, and ICAM-1 during primary MLC leads to down-regulation of secondary proliferative responses to Ag from the donor used for priming. Cells from pretreated cultures proliferated well, however, when stimulated with Ag from third party donors, mitogens, or mitogenic CD3 mAb. Because specific reactivity could be restored by addition of IL-2 to restimulation cultures, altered secondary responsiveness appeared to be caused by anergy and not by elimination of specific clones. Furthermore, specific down-regulation of alloresponsiveness was prevented by addition of IL-2 to primary cultures in the presence of mAb. Interference by mAb with either CD2/LFA-3, LFA-1/ICAM-1, CD2/LFA-1, or LFA-3/ICAM-1 had a substantial, though less pronounced effect on secondary responsiveness. After pretreatment with the Ab mixture, CTL generation was substantially but incompletely down-regulated against the original and third party donors. Because a decrease in the reactivity of unstimulated responders by culture was also observed, these findings might be explained by the loss of cytotoxic precursors after culturing under nonstimulating conditions. In conclusion, our data demonstrate that T cells enter a state of anergy when T cell activation is modulated by simultaneous interference with distinct adhesion molecules during Ag contact, which thus might reflect at least partly overlapping functions of particular receptor-ligand pairs in T cell costimulation.

Antibodies, Monoclonal↗
PubMed1993

Reactive oxygen product formation after Fc gamma receptor-mediated neutrophil activation by monomeric mouse IgG2a: implications for the generation of first dose effects after OKT3 treatment.

In the present study, we provide evidence that IgG2a monoclonal antibody (mAb) OKT3 is able to induce reactive oxygen intermediate (ROI) formation in polymorphonuclear leukocytes (PMN) when Fc gamma RIIIB as well as Fc gamma RII are bound concomitantly. Inhibition of binding to either Fc gamma R by specific mAb (3G8 or IV.3, respectively) resulted in complete abrogation of the OKT3-induced respiratory burst. The effect of OKT3 was independent from its specificity and thus also from its T cell-activating property, since nonbinding IgG2a isotype controls induced similar amounts of ROI. The IgG2b mAb BMA031 as well as the respective nonbinding isotype control were only minimally effective. With regard to the potential role of PMN activation in inflammation and tissue damage, our findings offer an extended explanation for the generation of initial adverse reactions to OKT3. Thus, one might speculate that the concerted action of cytokines liberated after its administration, what may lead to margination of leukocytes, and activation of PMN via Fc gamma R might produce first-dose reactions to OKT3 by directing radical-mediated damage against the endothelium.

Animals↗
PubMed1992

Insensitivity to cyclosporine may explain the HLA-DRw6 recipient effect.

Clinical as well as experimental studies have found an interindividual variability in the immunosuppressive effect of cyclosporine (CsA). In renal transplant patients treated with CsA and prednisolone alone, biopsy-verified rejections were significantly more frequent in DRw6-positive than in DRw6-negative graft recipients. The relative risk for developing a graft rejection independently of the CsA blood levels increased in HLA-DRw6-positive transplant patients. Although no statistical significance of the CsA levels within different DR phenotypes could be assessed, HLA-DR2-positive graft recipients with biopsy-verified rejection episodes had significantly lower CsA levels than DR2-negative patients (P = 0.01). Our results would indicate a very low CsA sensitivity of HLA-DRw6-positive graft recipients and might explain previous results describing an increased incidence of rejection and decreased graft survival rates in these patients.

Antilymphocyte Serum↗
PubMed1992

Cytokine release and dynamics of leukocyte populations after CD3/TCR monoclonal antibody treatment.

Cytokine release and clinical side effects resulting from the use of OKT3 and BMA 031 monoclonal antibodies in the treatment of kidney graft recipients were evaluated and compared. The rise observed in serum levels of interferon gamma. TNF alpha, and IL-8 was similar after administration of either monoclonal antibody. Furthermore, both OKT3 and BMA 031 resulted in rapid disappearance not only of virtually all T cells, but also of substantial percentages of all major leukocyte populations from the circulation; this effect is probably due to cytokine release activating endothelial cells and thereby causing extravasation even of leukocytes not specifically recognized by the administered antibodies. Evidence has thus been obtained that BMA 031 is as potent as OKT3 in inducing unequivocal signs of T cell activation in vivo. However, while OKT3 therapy was accompanied by adverse side effects in our study as in previous ones, we saw no such reactions in any of the patients receiving BMA 031. This contrast might be due to different mechanisms of leukocyte activation possibly inducing other mediators in the case of OKT3, which then, in combination with the cytokines, could generate treatment-associated morbidity.

Antibodies, Monoclonal↗
PubMed1992

[Human papillomavirus infection of the uterine cervix in immune suppressed women after kidney transplantation].

In 23 women, who had immunosuppressive therapy following renal transplantation, routine cytology and colposcopy were performed. Colposcopically directed punch biopsies were taken from the most suspect area. If no pathologic finding was evident during colposcopy a random sample was taken from the transformation zone. Histology revealed condylomatous lesions in seven cases. In two of the lesions, a CIN II was detected. To each woman with a renal allograft and therefore immunosuppressive therapy, two cases were matched for age, parity, and histological finding as a control group. Human papillomavirus (HPV) detection was performed by in-situ hybridisation. HPV infection rate in women with renal allografts was higher in biopsy specimens with condylomatous lesion (86%), as well as in tissue without condylomatous lesions (25%), compared to controls (56% and 9%). The high prevalence of cervical dysplasia and high HPV infection rate in women with immunosuppressive therapy, indicates the need for accurate and regular cytologic and colposcopic examinations in these patients.

Adolescent↗
PubMed1992

Evidence that sensitivity to cyclosporine is influenced by the HLA-DR phenotype of kidney graft recipients.

Clinical as well as experimental studies have shown a great interindividual variability in the immunosuppressive efficacy of CsA. Evaluating previous in vitro findings of a correlation between sensitivity of alloresponsiveness to CsA and the HLA-DR phenotype CsA levels were compared in kidney transplant recipients with and without rejections during the early posttransplant period and tested for a possible relationship to the HLA-DR phenotype of the recipient. In patients treated with CsA and prednisolone only, rejection frequency was significantly higher in HLA-DRw6 positive than in DRw6 negative graft recipients (77% vs. 53%, P = 0.045). In the DRw6 positive group incidence of rejection was independent of CsA blood levels, whereas in DRw6 negative patients frequency of rejection episodes decreased as a function of increasing CsA levels. Therefore the relative risk in developing graft rejection continuously increased in HLA-DRw6 positive patients. In HLA-DR2 positive graft recipients, however, a decrease in the relative risk could be observed with increasing CsA levels. Within patients with bioptically verified rejection episodes HLA-DR2 positive recipients had significantly lower CsA levels than DR2 negative patients (P = 0.01). In other HLA-DR phenotypes no association with CsA blood levels could be assessed. Also no statistically significant difference could be found in nonrejecting patients. These clinical findings demonstrate an association of sensitivity to immunosuppressive treatment and the HLA-DR phenotype of the graft recipient. Our results would indicate a very low CsA sensitivity of HLA-DRw6 positive graft recipients and thus might offer an explanation for previous findings about an increase in the incidence of rejection reported on those patients.

Adult↗
PubMed1992

Treatment of hyperlipidemic kidney graft recipients with lovastatin: effect on LDL-cholesterol and lipoprotein (a).

An increased incidence of hyperlipidemia places kidney graft recipients at increased risk for cardiovascular disease and may contribute to a decline in graft function. A study was undertaken to evaluate the safety and efficacy of lovastatin in these patients. Twelve kidney graft recipients with stable graft function and a cholesterol (chol) level over 250 mg/dl (6.46 mmol/l) were included. The lipid-lowering treatment consisted of 20 mg lovastatin daily, and all patients received immunosuppression with ciclosporin (CS) and prednisolone. Total chol decreased by 27% (300 +/- 56 to 219 +/- 28 mg/dl; 7.76 +/- 1.45 to 5.66 +/- 0.72 mmol/l; p < 0.01), LDL-chol by 35% (220 +/- 38 to 143 +/- 17 mg/dl; 5.69 +/- 0.98 to 3.70 +/- 0.44 mmol/l; p < 0.01) and triglycerides by 33% (207 +/- 127 to 138 +/- 56 mg/dl; 2.36 +/- 1.44 to 1.57 +/- 0.64 mmol/l; p < 0.05). HDL-chol increased by 10% (57 +/- 11 to 63 +/- 13 mg/dl; 1.47 +/- 0.28 to 1.63 +/- 0.34 mmol/l; NS). The ratio of total chol/HDL-chol, a generally accepted risk predictor of atherosclerosis, fell from 5.4 +/- 1.3 to 3.3 +/- 1.2, p < 0.01. Lipoprotein (a) [lp(a)], an independent risk predictor for atherosclerosis, was also evaluated at baseline and after 6 months of lovastatin treatment and showed a decrease of 39% (32.9 +/- 27.6 to 19.9 +/- 22.9 mg/dl; 0.85 +/- 0.71 to 0.51 +/- 0.59 mmol/l; p < 0.05). No adverse side effects were seen at this dosage, and hepatic and renal parameters remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗