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Biomedical subjects

L Révész

Publications and source records attributed to L Révész.

At least 19 recordsLinked to original sources
PubMed1999

Isolation and synthesis of a novel immunosuppressive 17alpha-substituted dammarane from the flour of the Palmyrah palm (Borassus flabellifer).

The novel triterpene 1 with a dammarane skeleton and a hitherto unknown 17alpha-substitution pattern has been isolated from the Palmyrah palm in low yield and prepared by synthesis in larger quantities. 1 was shown to be an extremely potent immunosuppressant in vitro (MLR; IC50 = 10 ng/ml) and in vivo (DTH; ED50 = 0.01 mg/kg p.o.). A glucocorticoid like activity is excluded.

Humans↗
PubMed1998

Solid phase synthesis of a biased mini tetrapeptoid-library for the discovery of monodentate ITAM mimics as ZAP-70 inhibitors.

The biased library was composed of a novel phosphotyrosine mimic fixed in the P1 position of a tetrapeptoid and combined with three lipophilic N-substituents at the remaining positions giving a total of 27 single compounds. Screening for ZAP-70 antagonism identified 8 as a novel selective monodentate ZAP-70 antagonist and lead in the search for new immunosuppressive drugs.

Humans↗
PubMed1995

Reduction of inflammation and pyrexia in the rat by oral administration of SDZ 224-015, an inhibitor of the interleukin-1 beta converting enzyme.

1. The aim of this study was to determine whether a synthetic inhibitor of the interleukin-1 beta converting enzyme (ICE) displays oral activity in models of inflammation. 2. To this end, the ICE inhibitor, SDZ 224-015, was examined in rat paw oedema, pyrexia and nociception tests. 3. SDZ 224-015 (0.3-300 micrograms kg-1) potently reduced carrageenin-induced paw oedema, with an oral ED50 of approximately 25 micrograms kg-1. This effect was independent of endogenous glucocorticoid, as shown by retention of activity upon adrenalectomy. 4. Pyrexia induced by lipopolysaccharide (0.1 mg kg-1 s.c.) or by interleukin-1 beta (100 ng i.v.) was also reduced, over a similar dose-range to oedema (oral ED50s 11 micrograms kg-1 and 4 micrograms kg-1 respectively). 5. SDZ 224-015 (0.2-5 mg kg-1, p.o.) displayed analgesic activity in the Randall-Selitto yeast-inflamed paw pressure test, significant at a dose of 1 mg kg-1, p.o. 6. Thus, SDZ 224-015 has potent oral activity in several acute models for inflammation, suggesting that ICE inhibitors may constitute a novel type of anti-inflammatory agent.

Administration, Oral↗
PubMed1994

Selective toxicity of buthionine sulfoximine (BSO) to melanoma cells in vitro and in vivo.

PURPOSE: Glutathione (GSH) was found to occur in relatively high concentrations in melanoma cells. The purpose of this study was to test the possible cytotoxic effects of an artificial decrease of the elevated GSH level. METHODS AND MATERIALS: The tests were made in vitro and in vivo. In the former case, a total of 11 rodent and human cell lines were studied of which seven were derived from melanomas. After treatment with buthionine sulfoximine (BSO), the decrease of GSH content of the cells and their clonogenic survival was determined. In the in vivo system, single cell suspensions of a subline of the B16 mouse melanoma were injected intravenously into immunocompetent and preirradiated recipients which were subsequently treated with BSO intraperitoneally. Survival time, formation of lung colonies and the weight of metastatic tumor mass in the lungs were the criteria of the BSO effect on the tumor cells. RESULTS: The decrease of the GSH level by BSO was associated with impaired clonogenic survival of the melanoma cells in vitro. Nonmelanoma cells were less affected. BSO treatment of mice inoculated intravenously with melanoma cells resulted in prolonged survival of the animals and impaired metastatic spread of the tumor cells. CONCLUSION: Melanoma cells are particularly sensitive to disturbance of GSH metabolism by treatment with BSO. In view of this selective cytotoxicity of BSO, treatment with this substance may afford a promising therapeutic potential for melanoma.

Animals↗
PubMed1993

Vascular density and the response of breast carcinomas to mastectomy and adjuvant chemotherapy.

Using morphometric analysis of histological preparations, in a retrospective study vascular indices, expressing the extent of vascularisation, were determined for a number of mammary carcinomas. The indices were found to be related to the survival of the patients treated with modified radical mastectomy in combination with pre- and postoperative chemotherapy, the cases with low indices having the shorter survival. The impaired access of the cytotoxic agents to cells in the deficiently vascularised tumours was considered as an explanation. It was concluded that determination of vascular density in tumours may have a prognostic value in regard to the treatment response, and may be helpful in choosing the appropriate treatment.

Adult↗
PubMed1993

The 'X model': a modified version of the competition theory.

In 1985, Edgren et al. proposed a modified version of the competition theory to explain the interaction of sensitizers and protectors with target molecules damaged by radiation, which was designated the 'X' model. This model incorporates concepts which have been considered previously, namely that a type of radiation damage exists which cannot be chemically repaired, and that cells may contain a naturally occurring sensitizer. The model leads to testable predictions, such as, e.g. the crossing of 'K curves' when the level of protection is varied. It can only be applied to the immediate effects of radiation, i.e. before enzymatic reactions play a part. The present paper is a summary of work carried out since 1985 to test the predictions of the 'X' model and an exposition of the related algebra.

Animals↗
PubMed1991

Radioprotection by dithiothreitol (DTT) at varying oxygen concentrations: predictions of a modified competition model and theory evaluation.

Cultures of Chinese hamster cells were treated with dithiothreitol (DTT) at varying concentrations, and exposed to radiation aerobically or at various oxygen tensions. The extent of radioprotection by DTT was calculated using the yield of DNA strand breaks as a measure of the radiation response. The curve of protection factors (PF) had a specific pattern, characterized by low PF values at low and high oxygen tensions with a peak at an intermediate tension. The peak value of the PF was increased and shifted to higher oxygen tensions as DTT concentrations increased. The experimentally observed pattern of the PF curves is incompatible with the Alper model of the competition hypothesis, which assumes that the entire radiation injury can be modified by sensitizers or protectors. On the other hand, the pattern is consistent with a model (X model) which is based upon a modification of the original hypothesis and assumes two types of radiation injury, only one of which is modifiable.

Animals↗
PubMed1990

Radiosensitization by oxygen and radioprotection by thiols: analysis of the combined action according to a modified competition model.

Cultures of Chinese hamster fibroblasts were treated with dithiothreitol (DTT) and irradiated under aerobic or hypoxic conditions. Protection factors (PF) and oxygen enhancement ratios (OER) were calculated with DNA breakage as the criterion of the radiation effects, and related to the intracellular concentration of non-protein-bound thiols (NPSH). When the increment of the cellular NPSH was in a low concentration range, the PF values were smaller for aerobically than for hypoxically irradiated cells. In contrast, in the case of cells with a large increase in NPSH concentration, the PF values for the hypoxically irradiated cells were smaller. As a consequence the PF curve of the hypoxically and aerobically exposed cells crossed, and OER values followed a bell-shaped curve with respect to increasing cellular NPSH concentrations. The observations could be explained by assuming a competition between the damage-restituting and damage-fixing reactants, and postulating that only a certain proportion of the damaged targets is reparable.

Animals↗
PubMed1990

Significance of oxygen availability for release of oxygen free radicals and lysozyme by neutrophils.

Neutrophilic granulocytes were exposed to an atmosphere of nearly 100% oxygen (hyperoxia) for one hour. The nitroblue tetrazolium (NBT) reduction, reflecting oxygen radical release, was decreased both in resting and stimulated cells, but lysozyme release was unchanged. Short time exposure of patients to oxygen hypertension might therefore be beneficial as therapy, in conditions where reduced production of oxygen radicals is required. The NBT reduction of resting and stimulated neutrophils in an atmosphere of purified argon (hypoxia) was also considerably decreased, and the lysozyme release unchanged. This reflects the anaerobic conditions in abscesses, where the contribution of neutrophil oxygen metabolites to the killing of microorganism might be reduced.

Cell Hypoxia↗
PubMed1989

Variation of vascular density within and between tumors of the uterine cervix and its predictive value for radiotherapy.

Vascular density in different regions of a number of uterine cervix carcinomas was determined by morphometric analysis of stained histologic sections. Variance analysis indicated a larger inter- than intra-tumoral inhomogeneity of the vasculature, suggesting a certain individual vascularization pattern in these tumors. As indicated by a retrospective study of archival biopsies, this pattern has a predictive value in regard to the efficacy of radiotherapy.

Carcinoma, Squamous Cell↗
PubMed1989

Cellular glutathione content and K values. II.

After exposure to radiation in the presence of different oxygen concentrations, the OER values were determined for human fibroblasts cell strains with differing intrinsic GSH content, and cells depleted of GSH to different extent by treatment with BSO. The yield of DNA single-strand breaks was used as the measure of radiosensitivity. The K values were found to be related specifically to the GSH concentration in the cell nuclei. A good agreement was found between the experimental observations and the prediction of a variant of the competition model in which a second type of damage, not influenced by oxygen, was included.

DNA Damage↗
PubMed1989

Effects of the novel opiate antagonist, SDZ 210-096, on luteinizing hormone secretion in the rat.

SDZ 210-096 is a novel 14 beta-benzyl morphinan derivative with antagonistic actions at mu and kappa opiate receptors. In the present experiments this compound has been characterized for luteinizing hormone (LH) secretion-stimulating effects in a variety of experimental paradigms in the rat. In juvenile female rats, serum LH levels were elevated markedly after s.c. or p.o. administration of SDZ 210-096; ED50 was less than 1 mg/kg p.o. at 60 min. Similar effects were seen in the male rat, with p.o. ED50 values of 1.5 and 2.8 mg/kg at 60 and 120 min, respectively. Serum LH levels were likewise elevated by this compound in adult female rats (both proestrous and diestrous). SDZ 210-096 maintained its LH secretion-stimulating capability in both male and female rats after up to 10 days of administration. Its effects were inhibited in a competitive manner by a mu (SDZ 202-250) and a kappa (bremazocine) opiate agonist. Moderate effects on prolactin and adrenocorticotropic hormone secretion (inhibition and stimulation, respectively) were observed. SDZ 210-096 exhibited specific high affinity binding to brain opiate binding sites. These results demonstrate that in the rat SDZ 210-096 is a potent, p.o.-active LH secretion stimulator, effective after repeated as well as acute application.

Adrenocorticotropic Hormone↗
PubMed1988

Vascular density in carcinoma of the uterine cervix and its predictive value for radiotherapy.

The vascular density (VD) in stage-III tumors of the uterine cervix was determined by morphometric analysis of histologic, Masson-trichrome stained sections prepared from biopsies. In a retrospective study, VD was found to be related to results of radiotherapy, larger VD being associated with prolonged survival, in agreement with similar observations made earlier with stage-IB and -IIA tumors of the cervix. In a complementary study the variation of VD within tumors was investigated in relation to the variation between tumors using surgically removed cervical carcinomas in stage IB. Statistically significant F-ratios were calculated, suggesting a more or less individual pattern of vascularization of the tumors despite a considerable intra-tumoral heterogeneity of the vasculature. It is concluded that VD may reflect oxygenation of neoplastic tissue, and may have a predictive value in regard to the response of tumors to irradiation.

Biopsy↗
PubMed1988

Vascularization and curability of stage III and IV nasopharyngeal tumors.

In a retrospective study the capillary density was determined in biopsies from 25 cases of nasopharyngeal tumor, stages III and IV. Determinations were made on stained histological sections by counting the capillaries within a standard field size and at standard magnification. A statistically significant correlation was found to exist between capillary density and eventually with chemotherapy. No correlation between survival and age or sex of the patients, or stage of tumor, was noted. It is concluded that capillary density in nasopharyngeal tumors has a predictive value.

Adult↗
PubMed1988

Prognostic significance of vascular density and a malignancy grading in radiation treated uterine cervix carcinoma.

In a retrospective study of 95 patients with squamous cell carcinoma of the uterine cervix (Stage IB, IIA, III) treated by radiation only, pretreatment biopsy material was used for assessment of the prognostic value of histopathological multifactorial malignancy grading and a morphometric estimation of vascular density in stroma. By comparison of the two systems, vascular density has been proved superior to malignancy grading with respect to prognostic value.

Biopsy↗
PubMed1987

Advances in hypoxyradiotherapy.

Observations in animal experiments and in Phase I clinical trials on the effect of breathing 8-10% oxygen are summarized. The animal tests indicated that the hypoxia induced in this way for periods varying between 10-45 minutes had a radioprotective effect on normal tissues. Patients tolerated the hypoxic treatment given for 15 minutes without any acute or late complications. Phase II trials have been started to test the effect of hypoxic radiotherapy in administering a larger total tumor dose than in conventional radiotherapy.

Animals↗