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Biomedical subjects

J Schindler

Publications and source records attributed to J Schindler.

At least 55 records · Page 3Linked to original sources

Plasma glutamate--a prognostic marker of cancer and of other immunodeficiency syndromes?

Elevated plasma levels of glutamate (GLU) have been reported to occur in patients with malignancies and other immunodeficiency syndromes (IDS). To evaluate, whether GLU is useful as prognostic indicator, the plasma concentrations were determined in patients with colorectal carcinoma (CRC), with breast cancer (BRC), and with HIV-infection (HIV). The results were correlated with the disease-stages, and compared with data obtained from patients with benign diseases of the same organ, as well as from sex-matched healthy volunteers. GLU concentrations (volunteers: 27.4 +/- 17.6 mumol/l) were elevated in all BRC patients (range of mean values: 53.5-83.2 mumol/l), in CRC patients with T2-T4-tumours (means: 46.8-85.9), and in HIV+ patients of stage WR 5, 6 (means: 53.9-69.7 mumol/l). All CRC- and BRC-patients with metastases showed highly significant elevations of GLU concentrations (p less than 0.001), but there were no direct correlations between disease stages and GLU levels. Pre-operative patients with benign diseases (diverticulitis, adenoma = GID; and mastopathy = MTP) showed increased GLU levels, which were comparable to those of the tumour patients. The glutamine/GLU ratios (volunteers: 19.3 +/- 15.0) were decreased only in HIV-WR 6 (7.6 +/- 2.1), and BRC-stage 4 (8.0 +/- 1.7). From these results we deduce that the plasma GLU concentrations do not allow a discrimination either between patients with malignancies and without, and between persons of different disease stages.

Aged↗

[Dosimetric studies of 192Ir line sources and the mathematical presentation of the dose distribution].

The dose distribution of a "line-shaped" 192Ir-source was measured in 1,152 measuring points in a water phantom. Using regression analysis the analytical description of dose distribution was obtained. Accomplished comparison measurings with a solid phantom of miramide in 45 measuring points show that the dose distribution can be reproduced well by solid phantom measurings. Taking an ideal line source distribution as a basis, the r-dependence of correction factor, obtained by regression analysis, refers to a dispersion effect. The angle-dependent deviation of dose distribution from the ideal line source can be described by cos-terms with the single and double angle between line source axis and measuring point.

Brachytherapy↗

[A standard code for naming microbes].

The author suggests a code for communication and processing of data which involves the formation of code names, in particular of microorganisms. These code is reached after agreement, made compulsory and then strictly respected. The principle for the formation of the code is relative comprehensibility, simplicity and orientation on a given area of application. The generation of the code is made by a computer.

Information Systems↗

Plasma amino acid pattern of patients with HIV infection.

We measured the free amino acids in plasma of 58 patients with HIV infection and in six persons in the risk group. The HIV+ patients had significantly increased concentrations of arginine, phenylalanine, and glutamate in comparison with both age- and sex-matched controls and the members of the risk group. Glutamate concentrations increased only in an advanced stage of the disease (WR 5 and 6 of the Walter Reed staging classification), whereas arginine and phenylalanine increased independently of the stage. There was no correlation between the amino acid concentrations and the number of T4 and T8 lymphocytes, the sedimentation rate, and the existence or absence of Kaposi's sarcoma. The amino acid pattern of HIV-infected persons is similar to that of cancer patients or those with other immune deficiencies.

Acquired Immunodeficiency Syndrome↗

Interferon gamma in rheumatoid arthritis--a double blind study comparing human recombinant interferon gamma with placebo.

A double blind trial comparing recominant interferon gamma (IFN gamma) with placebo in rheumatoid arthritis is presented. Twenty-six patients entered the study and 22 completed the 6-month period. IFN gamma was administered subcutaneously as was placebo; the 1st week, patients treated with the active compound received a daily subcutaneous injection of 100 micrograms of IFN gamma and for the following 23 weeks the schedule was decreased to 2 injections of 100 micrograms every week. No serious side effects were observed. After Week 24 the group treated with the active compound showed a significant decrease of the joint tenderness score and the placebo group showed a significant increase of the number of subcutaneous nodules. All other variables shifted in favour of the active compound but not significantly. More double blind trials with a larger number of patients and using other treatment schedules or other routes of administration are required.

Arthritis, Rheumatoid↗

A new member of the family Enterobacteriaceae--Pragia fontium.

Twenty isolates of the new genus and species Pragia fontium producing H2S were biochemically characterized: they gave positive gluconate oxidation, utilized Simmons citrate and 14 of them hydrolysed esculin. One of them did not produce hydrogen sulfide. Their biochemical activity was low: they did not ferment lactose, adonitol, arabinose, cellobiose, dextrin, dulcitol, erythritol, inulin, maltose, mannitol, mannose, melezitose, melibiose, raffinose, rhamnose, sorbitol, sorbose, starch, sucrose or trehalose. The habitat of Pragia fontium is drinking water, with an exception: the last strain was found in a stool specimen of a healthy woman. The type culture is the first isolate No. 20125-HG 16. It is deposited in Prague (CNCTC) under the designation Eb 11/82.

Cytosine↗

Systematic preclinical study on the therapeutic properties of recombinant human interleukin 2 for the treatment of metastatic disease.

The availability of recombinant human interleukin 2 (rH IL 2) has resulted in its clinical utilization both as a single agent and in combination with lymphokine-activated killer cells. In this report, we discuss the effects of rH IL 2, administered by various routes, on effector cell function, pharmacokinetics and bioavailability, and therapeutic activity. Studies of the pharmacokinetics of in vitro natural killer (NK) cell augmentation by rH IL 2 revealed that a short exposure to high levels of rH IL 2 can augment NK cell activity; however, a prolonged exposure (greater than 12 h) was required to augment NK cell activity at lower doses of rH IL 2. These observations suggested that chronic administration of rH IL 2 might improve immunomodulatory and therapeutic activity. This hypothesis was supported by the results of studies in which we treated experimental and spontaneous metastasis, which revealed that the daily i.p. administration of rH IL 2 resulted in significantly greater therapeutic activity than administration three times/week. The therapeutic protocol for daily i.p. administration had a biphasic dosage optimum, such that low dose therapeutic activity was observed at approximately 100-1000 units/animal in the treatment of experimental metastases or 10 to 100 units/animal in the treatment of spontaneous metastases. There was a second dosage optimum at greater than or equal to 100,000 units/animal rH IL 2 delivered i.p. on a daily basis. Intermediate doses had no significant therapeutic activity. Additional studies revealed that low dose therapeutic activity was not observed in nude mice. In contrast, therapeutic activity was observed in nude mice at high doses of rH IL 2 suggesting that low dose activity was associated with a T-cell-mediated effect, whereas high dose activity may have been mediated by NK or lymphokine-activated killer-like cells. This observation was in agreement with the dose response for T-cell adjuvant activity supporting the hypothesis that low dose therapeutic activity was T-cell associated, because adjuvant activity was observed when rH IL 2 was given daily at approximately 100 units/animal for 3 days, and higher doses had no activity or had a suppressive effect. Because we were concerned about the pharmacological aspects of rH IL 2 treatment, we also examined its therapeutic properties after continuous administration i.p. by osmotic pumps. Under these conditions, therapeutic activity was observed after administration of 600 units/h, whereas lower or higher doses did not have significant therapeutic activity.

Adjuvants, Immunologic↗

In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes.

To determine the potential immunotherapeutic role of interferon-gamma (IFN-gamma) as a mononuclear phagocyte-activating agent, we examined the effector cell function of peripheral blood monocytes from healthy donors and acquired immunodeficiency syndrome (AIDS) patients after either in vitro and/or in vivo treatment with recombinant (r) IFN-gamma. When assayed immediately after a 24-hr in vitro pulse with 300 U/ml, normal and AIDS monocytes behaved similarly with little augmentation of their intrinsically high levels of H2O2 release and activity against Toxoplasma gondii; in contrast, activity toward the more resistant intracellular pathogen, Leishmania donovani, was appreciably enhanced by rIFN-gamma. In addition, upon testing 4 to 6 days after in vitro pulsing, both normal and AIDS monocytes showed clear evidence of persistent activation in all three assays. The capacity of IFN-gamma to similarly activate monocytes in vivo was confirmed in all ten treated AIDS patients by examining cells before and after 24-hr infusions of 0.03 and 0.5 mg of rIFN-gamma/square meter (M2) of body surface area. For postinfusion monocytes tested after 1 day in culture, H2O2 release and antitoxoplasma activity were essentially unchanged, but antileishmanial effects were augmented. After 5 to 7 days in culture, monocytes from treated patients showed 3.2- to 5.9-fold increases in H2O2-releasing capacity and increases of 49 to 68% and 35 to 61% in intracellular activity against T. gondii and L. donovani, respectively. These results indicate that the human monocyte can be induced by rIFN-gamma to express signs of both immediate and persistent activation and suggest that, as a direct activator of mononuclear phagocytes, rIFN-gamma may also have potential as an immunotherapeutic agent for patients with intracellular infections.

Acquired Immunodeficiency Syndrome↗

Transglutaminase activity and embryonal carcinoma cell differentiation.

Murine embryonal carcinoma (EC) cells induced to differentiate by retinoic acid (RA) modulate transglutaminase (TGase) activity shortly after exposure to the inducer. Compounds that inhibit TGase enzyme activity in vitro can successfully block RA induced EC cell differentiation in culture. These observations suggest that TGase may play a role in mediating RA induced EC cell differentiation.

Animals↗

Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system.

We treated 18 clinically definite relapsing-remitting MS patients with recombinant gamma interferon in a pilot study designed to evaluate toxicity and dosage. Patients received low (1 microgram), intermediate (30 micrograms), or high (1,000 micrograms) doses of interferon by intravenous infusion twice a week for 4 weeks. Serum levels of gamma interferon were proportional to dose and no interferon was detected in CSF. Seven of the 18 patients had exacerbations during treatment, a significant increase compared with the prestudy exacerbation rate (p less than 0.01). Exacerbations occurred in all three dosage groups and were not precipitated by fever or other dose-dependent side effects. There were significant increases in circulating monocytes bearing class II (HLA-DR) surface antigen, in the proliferative responses of peripheral blood leukocytes, and in natural killer cell activity. These results show that systemic administration of gamma interferon has pronounced effects on cellular immunity in MS and on disease activity within the CNS, suggesting that the attacks induced during treatment were immunologically mediated. Gamma interferon is unsuitable for use as a therapeutic agent in MS. Agents that specifically inhibit gamma interferon production or counteract its effects on immune cells should be investigated as candidates for experimental therapy.

Adult↗

Incidence of anti HIV antibodies and viral antigen in standard and control sera.

Most material used for control and calibration in a clinical laboratory is based on pool sera of human origin, guaranteed to be HBsAg-free. Since little information is available on the potential infectivity of HIV, the causative agent of acquired immunodeficiency syndrome (AIDS), 54 control and calibration sera, in routine use, were investigated for the incidence of antibodies to HIV by means of Elisa. Sixteen test specimens ( = 30%) gave positive or borderline Elisa results and were further analysed by immunoblotting, resulting in 15 samples all recognizing gp 160 and partially the p 24, p 31, p 55, p 64 and gp 120 band. Only one sample with borderline Elisa result was negative by this assay. Furthermore, all sera were examined for the presence of viral antigen by a solid phase Elisa. All samples under investigation gave negative antigen Elisa results. Bearing in mind that the sensitivity of this assay is limited to 10 micrograms/l of viral antigen, no conclusion on infectivity should be drawn. The high incidence of HIV-antibodies in the sera investigated demands that this material should be handled with special care by laboratory personnel.

Antibodies, Viral↗

Prevention of nephrotoxic cyclosporine peak concentrations by daily drug division in 3 equal oral portions.

Nephrotoxicity is the main side effect of cyclosporine therapy. In this study 2 groups consisting of 6 kidney transplant recipients were investigated. The oral cyclosporine daily dose was in the first group 13 mg/kg, in the second 11 mg/kg, respectively. In both groups, the daily dose was divided on the first day of investigation in 2 equal portions given at an interval of 12 hours. On the second day, the same dose was divided in 3 equal portions given at an interval of 8 hours. After cyclosporine administration twice a day very high blood cyclosporine peak concentrations (two to three times higher than the therapeutic range) were measured. These potential nephrotoxic cyclosporine concentrations could be prevented by cyclosporine application in 3 equal portions. A reduction of the daily dose in the early period after kidney transplantation to a starting daily dose of 12 mg/kg or even 10 mg/kg can be recommended.

Adult↗

Effect of interleukin-2 on diabetes in the BB/Wor rat.

Young diabetes prone BB/Wor rats were treated for 4-7 weeks with low dose (1,000 units/week) or high dose (75,000 units/week) recombinant human interleukin-2 (IL-2) and observed through 150 days of age for the development of spontaneous diabetes mellitus. Comparing treated rats with controls, it was found that IL-2 did not affect the cumulative incidence of diabetes, the age at onset of the disease, or peripheral lymphocyte subset numbers. High dose IL-2 administered to diabetes resistant BB/Wor rats also failed to induce the disease.

Animals↗