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Biomedical subjects

O Klein

Publications and source records attributed to O Klein.

At least 91 records · Page 5Linked to original sources
PubMed1992

Activated eosinophils in adult coeliac disease: evidence for a local release of major basic protein.

The eosinophil population is increased in the jejunal mucosa of patients with coeliac disease. Eosinophils may participate in the mucosal damage by releasing their granule components that have cytotoxic properties such as eosinophil cationic protein (ECP) and major basic protein (MBP). This study aimed to assess the presence of ECP and MBP in the jejunal mucosa of 10 adult patients with active coeliac disease who presented with villous flattening. Endoscopic jejunal biopsy specimens were obtained from macroscopically flattened jejunal mucosa and were processed for ultrastructural study and immunogold labelling using anti-MBP, anti-ECP, and anti-IgA antibodies. Numerous eosinophils were found in the upper part of the lamina propria and showed two types of morphological change: some were lytic and others exhibited ultrastructural signs of activation, containing altered granules with fading of the central core. IgA plasma cells were intermingled with eosinophils and had dense deposits on the external side of their cytoplasmic membrane. MBP was detected in central cores of granules but also diffusely in their matrix and in tight association with dense extracellular deposits. Conversely, ECP was detected only in the matrix of eosinophil granules. This study showed that numerous eosinophils are in an activated state in the mucosa of patients with active coeliac disease and release cytotoxic proteins such as MBP, which could contribute to the mucosal damage. The observation that eosinophils and IgA plasmocytes were closely associated in the mucosa supports a role for IgA in eosinophil recruitment and activation in coeliac disease.

Adolescent↗
PubMed1992

Cellular functions related to metastasis differing between low- and high-malignancy variants of AKR lymphoma.

Two AKR lymphoma variants of low (LM) and high (HM) malignancy were characterized for cell properties important for metastatic capacity. Previous data suggested that these murine lymphoma variants differed in the late phase of metastasis. In the present study we attempted to determine more accurately the stage in which they differ. The HM cells attached less efficiently than the LM ones to both endothelial cells (5 times) and extracellular matrix (twice), possibly indicating a more efficient extravasation capacity of the HM cells. The level of heparinase was low in the two variant cells. Attachment to liver sections was, however, more efficient with the HM than with the LM cells.

AKR murine leukemia virus↗
PubMed1992

Effect of a membrane-active agent on uptake of adriamycin in Lewis lung carcinoma cells derived from 'primary' and 'metastatic' growths.

The treatment of metastatic growth still constitutes a challenge for cancer research. Tumor progression is often accompanied by a loss in sensitivity to previously efficient drugs. Decreased intracellular accumulation of cytotoxic agents is probably the major reason for drug resistance, although other mechanisms have also been described. Properties of the cell membrane have been shown to determine the metastatic phenotype. This cellular organelle is also responsible for the multiple drug resistance phenomenon. Membrane-active agents may increase cell permeability to drugs, counteracting thereby drug resistance. In the present study the effect of the nonionic detergent Tween 80 on sensitivity to adriamycin (ADR) of cells derived from Lewis lung carcinoma 'primary tumors' (PT)-the local growth following subcutaneous inoculation - and 'metastatic tumors' (MT) - lung tumors which develop following intravenous injection - was compared. Flow cytometry analysis demonstrated several differences between cells derived from the PT and the MT: (1) single ADR treatment showed that MT cells possessed a lower percentage of a high ADR permeability subpopulation than PT cells; (2) a dose-dependent shift to a higher ADR accumulating population was seen in the presence of Tween 80 for both cell types. However, the increase in percentage of high ADR permeability cells was more pronounced in MT (up to x4.7) than in PT (up to x1.3) cells. This differential effect of the membrane-acting agent was evident at various ADR (10-50 micrograms) and Tween 80 (0.1-0.4%) concentrations. The present results corroborate previous data obtained in our group in another tumor progression model, AKR lymphoma.

Animals↗
PubMed1992

Effects of induction of labor with prostaglandin E2 on fetal breathing and body movements: controlled, randomized, double-blind study.

OBJECTIVE: To evaluate the effects of prostaglandin (PG) E2, given for induction of labor at term, on fetal breathing and body movements. METHODS: Eighteen women with term pregnancies, mild gestational hypertension, intact membranes, and unripe cervices who were not in labor participated in this study. After a 60-minute baseline ultrasound examination of fetal chest and body movements, recorded on videotape, the patients were randomly assigned to either 3 mg intravaginal PGE2 tablets or controls (placebo intravaginal tablets). Following tablet insertion and a 3-hour observation time, a second 60-minute ultrasound recording of fetal movements was taped. The videotape recordings were interpreted according to the total amount of time occupied by fetal body movements and fetal breathing movements. RESULTS: There was a total of 2180 minutes of ultrasound tape recordings, with 136.2 minutes of fetal body movements (6.2%) and 207.8 minutes of fetal breathing movements (9.5%). Mean (+/- standard deviation) observation times per patient before and after tablet insertion were 60.3 +/- 1.2 and 56.4 +/- 1.2 minutes for the PGE2 group and 60.1 +/- 1.3 and 60.4 +/- 1.1 minutes for the control group. Three hours after PGE2 insertion, there were significant decreases in the percentage of time occupied by body movements (7.8 +/- 3.1 versus 3.4 +/- 2.0%; P < .003) and breathing movements (10.6 +/- 8.6 versus 3.9 +/- 2.3%; P < .007). Three hours after tablet insertion, there were statistically significant decreases in the percentage of time occupied by body movements (P < .025) and breathing movements (P < .01) between the control and study groups. CONCLUSION: Induction of labor with intravaginal PGE2 tablets inhibits fetal body and breathing movements. The effects could be due to direct action on the fetus or indirect effects of PGE2 (through uterine contraction and/or endogenous PG).

Dinoprostone↗
PubMed1992

Treatment of refractory colorectal carcinomas with fluorouracil, folinic acid, and interferon alfa-2a.

Interferon has been shown to augment the cytotoxic effects of fluorouracil (5-FU) against colon cancer in vitro and possibly in vivo. Therefore a pilot study was initiated to evaluate the effects of the combination 5-FU/FA/interferon alfa (IFN-alpha) in colorectal adenocarcinomas refractory to first-line therapy with 5-FU/FA. Eleven patients with rectum cancer and four patients with colon cancer were treated according to the following schedule: 9 million units IFN-alpha subcutaneous three times a week; 500 mg/m2 5-FU via an intravenous bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of FA, once a week. Of 15 patients, one had a minor response, one had a disease stabilization, and three had a mixed response. No complete or partial remissions were seen. Looking at the sensitivity of lung metastases (three of three), the regressions can be explained through the additive effect of IFN-alpha to 5-FU/FA. Although minimal side effects (World Health Organization classification) were observed, most patients experienced a reduction of well-being.

Adult↗
PubMed1992

Combination fluorouracil, folinic acid, and interferon alfa-2a: an active regimen in advanced pancreatic carcinoma.

Based on promising results with 5-FU/FA or 5-FU/IFN-alpha in colorectal cancer, a pilot study was initiated to evaluate the effects of the combination 5-FU/FA/interferon alfa (IFN-alpha) in patients with advanced pancreatic cancer. Patients received 9 million units (MU) IFN-alpha subcutaneously three times a week or 6 MU IFN-alpha once a week; 500 mg/m2 5-FU via an intravenous bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of FA, once a week. Fourteen patients, all previously untreated with chemotherapy, were enrolled; 13 (two females/11 males) were evaluable for response and toxicity (one too early). The median performance status was 80% (range, 60 to 100) and the median age 62 years. Besides the inoperable primary tumor, metastatic sites were liver, lung, and peritoneum. Three of 13 patients had a partial remission, three of 13 patients a minor response, and four of 13 patients no change. Three patients had progressive disease. Until now, no complete remission was seen. Median duration of response was 4+ months; median survival has not been reached yet. Of all patients there were three instances of World Health Organization grade 3 toxicity: fatigue (one of 13), nausea (one of 13), and diarrhea (one of 13); grade 4 toxicity did not occur. Although overall toxicity was moderate, most patients experienced a reduction of well-being. Therefore in all patients the dose of IFN was reduced (from 3 x 9 MU/week to 1 x 6 MU/week). Our preliminary data suggest that biochemical modulation of 5-FU with FA and IFN-alpha (reduced dosage) is effective in pancreatic cancer with moderate toxicity, warranting further study.

Adult↗
PubMed1992

Differential metastatic capacity of three AKR lymphoma variants.

The comprehension of tumour progression has advanced due to the use of various models, the most rewarding being probably the study of malignancy variants derived from the same tumour. In the present study the biological behaviours of three AKR lymphoma variants were compared. The three variants, TAU-33, TAU-38 and TAU-39, differed markedly in biological behaviour. The TAU-39 variant formed very large 'primary tumours', TAU-33 produced local growths of intermediate size, and TAU-38 formed small s.c. tumours. However, the metastatic potentials of the variants were inversely related to their ability to produce local tumours. According to various parameters (spread to organs, cachexia and mice mortality rate), the variant of highest metastatic potential was TAU-38, the one of intermediate ability TAU-33 and the TAU-39 had the least aggressive behaviour. A lack of difference in invasive capacity as well as a similar ranking of malignancy by both s.c. and i.v. inoculation indicate a differential behaviour in late metastasis phase. Tumour progression models may contribute to a better understanding of this threatening process and to testing of new treatment modalities suitable for cancer at different stages.

Animals↗
PubMed1992

Use of antimicrobial agents to treat central nervous system infection.

When dealing with infections of the central nervous system (CNS), the clinician is often faced with a daunting diagnostic and therapeutic challenge. The clinical presentation can vary from an insidious course that allows time for a full diagnostic examination to fulminant catastrophic events that require immediate therapeutic intervention. Fortunately, a thorough clinical evaluation combined with current laboratory and imaging techniques often allows for a prompt provisional diagnosis of infection. Clinical experience and scientific investigation have laid the basis for rational empiric antimicrobial therapy of CNS infection. The role of antibiotics in the treatment of CNS infections is reviewed and updated, emphasizing current rationale for empiric therapy as well as the proper use of specific antibiotics for specific pathogens.

Anti-Bacterial Agents↗
PubMed1991

Candida arthritis: cellular immune responses of synovial fluid and peripheral blood lymphocytes to Candida albicans.

A case of septic Candida albicans arthritis of the knee in a patient with systemic candidiasis is presented. Systemic and intra-articular cellular immune responses to C albicans and various bacterial antigens were monitored for 15 weeks. It is shown that the candida induced blastogenesis of synovial fluid lymphocytes was much more stimulated than that of peripheral blood lymphocytes, and that the proportion of activated cells expressing HLA class II antigens was markedly increased in the synovial fluid. Strong cellular immune responses to Candida albicans could still be shown many weeks after the synovial fluid aspirates had become sterile. For the first time synovial fluid derived, CD4 positive T lymphocyte clones with specificity for candida antigens were characterised and further propagated in vitro.

Antibodies, Monoclonal↗
PubMed1990

AKR lymphoma malignancy variants differing at late phase of metastasis.

The biological behavior of two AKR lymphoma variants, the TAU-39 and TAU-38, of low (LM) and high (HM) malignancy, respectively, has previously been described. In the present study an attempt was made to determine the phase in the metastatic process in which these variants differ. Two types of findings suggest that the two variants differ in the late phase of the process; (a) no difference in the degree of invasiveness of the primary tumor to the surrounding tissues has been found between the two variants, both being highly invasive; (b) comparison of malignant behavior in the "spontaneous metastasis" versus the "experimental metastasis" tests showed a similar ranking of malignancy of the two variants.

Animals↗
PubMed1990

[New aspects of intolerance of the aqueous iodinated x-ray contrast medium, adipiodone--fatal interaction of adipiodone-Ultrabil with the immunomodulators Corynebacterium parvum (CP) and Shigella dysenteriae endotoxin (LPS)].

The authors assume a new type of interaction of the aqueous X-ray contrast substance type adipiodone (Ultrabil 50% Spofa) with immunomodulators of Corynebacterium parvum (CP) and the endotoxin of Shigella dysenteriae (LPS). The fatal type of interaction developed regularly as a result of the concurrent i.v. administration of the X-ray contrast substance adipiodone with the endotoxin of Shigella dys. (LPS) to laboratory animals (mice) which had five days previously a single dose of Corynebacterium parvum (CP). The effect of the interaction was evaluated using LD50 of adipiodone (Ultrabil Spofa) which in interaction with the immunomodulators of CP and LPS was identical as the dose used in diagnostic practice. The authors considered the possible development of "oxygen stress" as a consequence interacting processes and complement activation.

Adjuvants, Immunologic↗
PubMed1990

Effect of hyperthermia and thermochemotherapy on primary and metastatic tumour cells of AKR lymphoma.

The cure of metastatic disease constitutes a serious problem. Recent findings showed cell membrane differences between slightly and highly metastasizing tumour cells, suggesting that since this cell organelle determines the metastatic phenotype, it might serve as a target for future drugs programmed against advanced cancer. The cell membrane has also been shown to be involved in the evolution of drug resistance which often accompanies tumour progression. In the present study, the effect of hyperthermia--an antitumoral treatment modality partly exerting its effect on the cell membrane--on primary and metastatic AKR lymphoma cells was compared. The effect of hyperthermia in conjunction with adriamycin (ADR) on the two cell types was also tested. Hyperthermic treatment, alone and in combination with ADR, was more effective in reducing the tumorigenicity of cells derived from metastatic tumours than of the primary tumour cells. Fluorescent microscopy and cytofluorometry showed that the increased effect of ADR by hyperthermia was due to an increased drug uptake at the supranormal temperature.

Animals↗