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Biomedical subjects

B Szende

Publications and source records attributed to B Szende.

At least 55 records · Page 3Linked to original sources
PubMed1999

Prevention of apoptosis reperfusion renal injury by calcium channel blockers.

Apoptosis has been shown in the literature to be the form of cell death occurring in renal tubular epithelial cells during the reperfusion phase after brief periods of renal ischaemia. In the present study apoptosis was examined in the rat kidney in the first 24 hours after 30 min ischaemia and apoptosis was influenced by administration of the Ca channel blockers Verapamil, Bepridil, Nifedipin and Sensit. Apoptosis was observed in the renal tubular cells two hours after the start of reperfusion and reached in maximum at hour 6. All above mentioned Ca channel blockers decreased the occurrence and degree of apoptosis.

Animals↗
PubMed1999

Prostatic intraepithelial neoplasia and apoptosis in benign prostatic hyperplasia before and after the Chernobyl accident in Ukraine.

The prevalence of prostatic intraepithelial neoplasia (PIN) in men who underwent surgery for benign prostatic hyperplasia (BPH) before and after the Chernobyl nuclear accident was studied. BPH samples were obtained by adenomectomy from 45 patients operated in 1984 before the accident (Group I), and 47 patients from the low contaminated Kiev City (Group II) and 76 from high contaminated area (Group III) operated between 1996 and 1998. Their BPH samples were examined histologically and immunohistochemically. The incidences of prostatic intraepithelial neoplasia (PIN) and high grade PIN (HGPIN) were 15.5 and 11.1% in Group I, 29.8 and 14.9% in Grpoup II, and 35. 5 and 19.7% in Group III. The difference between the incidences of PIN in Group I and III is significant (p<0.02). There was increased apoptosis in areas of PIN in Group II and III as compared to Group I (p<0.001). Since apoptosis has been shown to be associated with ionizing radiation and it is now found to be associated with PIN in patients diagnosed after the Chernobyl nuclear accident, this suggests that long-term low dose internal ionizing radiation potentially may cause prostate cancer.

Apoptosis↗
PubMed1999

A case of bilateral testicular lymphoma.

Authors report on a 75-year-old man with bilateral testicular lymphoma. He complained of painless right testicular enlargement. Orchidectomy was indicated by ultrasound examination and the diagnosis (large cell, non-Hodgkin lymphoma B-cell origin) was established by histology and immunohistochemistry. Two months later, the left testis enlarged, orchidectomy was performed, and a lymphoma with identical histology was found. PET revealed retroperitoneal spread of the tumor. Irradiation (18 Gy) was applied. Three months later, because of gastric metastases of the lymphoma the patient underwent CVP and CAVP (Cyclophosphamide, Adriablastin, Vincristin, Prednisolone) chemotherapy. Despite of the repeated courses, eleven months after the primary diagnosis the patient died due to of multiple metastases.

Aged↗
PubMed1999

MSC, a new benzoquinone-containing natural product with antimetastatic effect.

An orally applicable fermentation product of wheat germ containing 0.04% substituted benzoquinone (MSC) has been invented by Hungarian chemists under the trade name of AVEMAR. Oral administration (3 g/kg body weight) of MSC enhances blastic transformation of splenic lymphocytes in mice. The same treatment shortens the survival time of skin grafts in a co-isogenic mouse skin transplantation model, pointing to the immune-reconstructive effect of MSC. A highly significant antimetastatic effect of MSC has been observed in three metastasis models (3LL-HH, B16, HCR-25). The antimetastatic effect of MSC--besides the immune-reconstitution--may also be due to its cell adhesion inhibitory, cell proliferation inhibitory, apoptosis enhancing, and antioxidant characteristics, also observed in our in vitro experiments. It is even more noteworthy that combined treatment with MSC and one of the following antineoplastic agents (5-FU and DTIC)--both in wide use in every day clinical practice--exhibited a significantly enhanced antimetastatic effect in appropriate metastasis models (established from C38 mouse colon carcinoma and B16 mouse melanoma respectively) as compared to the effect elicited by any component of these therapeutic compositions (MSC + 5-FU and MSC + DTIC) administered alone. The results show that the fermented wheat germ extract (MSC) has more than an additive effect and synergistically enhanced the metastasis inhibitory effect of both antineoplastic agents studied till now. It is also worthy of mention that the synchronous treatment with MSC profoundly decreased the toxic side effects of the applied antineoplastic agents (decreased weight loss etc). Based on the biological effects of MSC--shown to be non-toxic by subacute toxicology studies--this product may be used as an adjuvant in the therapy of malignant neoplasia and other diseases caused by or following immune-deficiency.

Animals↗
PubMed1999

Apoptosis, mitosis, p53, bcl(2), Ki-67 and clinical outcome in prostate carcinoma treated by androgen ablation.

A prospective study on 16 patients with advanced (stage III and IV) prostate cancer was carried out. TNM stage, general clinical status, serum PSA level, the histological type and Gleason's grade of the tumor were registered. Total androgen blockade or single-drug therapy (flutamide) was performed. On average, 4.81 months after the start of therapy rebiopsy, serum PSA determination and general clinical examination were performed. Histologic examination before and after treatment of HE-stained slides, as well as apop-tag reaction to show apoptotic cells, p53, bcl(2), and Ki-67 immunostaining. Clinical improvement manifested by regression or lack of progression was observed in 10 patients. Increase of the apoptotic index and decrease of the mitotic index was detected in these cases. Serum PSA level decreased in all patients except in 3 fatal cases. The 6 clinically nonresponders who died after the second biopsy did not show an increased apoptotic or decreased mitotic index. Ki-67 positivity correlated well with the mitotic activity. Mutant p53 expression was higher in patients in whom antiandrogen therapy was ineffective. The bcl(2) expression was a characteristic of the tumors of patients who later died. These results show that the degree of induction of apoptosis in prostate carcinoma by hormonal therapy varies from case to case. A given prostate cancer patient's response to therapy may be predicted by following apoptotic and mitotic activity, as well as Ki-67 and p53 expression in repeated biopsies.

Adenocarcinoma↗
PubMed1999

A specifically radiolabeled somatostatin analog with strong antitumor activity induces apoptosis and accumulates in the cytosol and the nucleus of HT29 human colon carcinoma cells.

The new heptapeptide somatostatin analog TT-232 decreases proliferation of HT-29 human colon carcinoma cells in vitro by reducing mitotic and increasing apoptotic activity. We have synthesized and characterized a specifically tritium labeled 3H-Tyr3-TT-232 (30 Ci/mmol) to investigate the effect and the fate of this antitumor peptide on human colon tumor cells. 3H-labeled TT-232 could be detected on the cell surface, on cytoplasmic membranes and also in the nucleus of HT-29 cells, 1-6 h after the administration of 0.5 and 50 microg/mL [3H]TT-232. Binding and internalization of TT-232 to human colon tumor cells at a relatively high dose provide further evidence for the existence of low-affinity somatostatin receptors in such cells, which might mediate the apoptosis-inducing effect. Our data suggest the possible use of TT-232 in the treatment of human colon tumors.

Antineoplastic Agents↗
PubMed1999

[Preparation and characterization of potential antineoplastic agents].

A parallel combinatorial library of over sixteen hundred compounds has been designed and synthesized for the development of new potential peptidomimetic protein tyrosine kinase (PTK) inhibitor leads that is aimed for intervening with the substrate binding site of the pp60c-src enzyme. The new structures were based on known PTK inhibitors having at least two variously substituted aromatic moieties attached by spacer groups of different length and flexibility. Eleven bis-aryl type inhibitory compounds were found in the range of 18-100 micromolar IC50 concentrations from combinations of twelve different substituents. Molecular modeling of the active compounds showed a characteristic distance of 13-14 A between the farthest sp2 carbon atoms of the two aromatic rings. Conformational analysis of several peptide substrates recently found for pp60c-src PTK [5,6,7] showed that the energy minimized conformers had the same distance between two aromatic moieties. Several compounds in the library not only showed remarkable PTK inhibitory activity but also a significant apoptosis inducing effect on HT-29 human colon tumor cells.

Antineoplastic Agents↗
PubMed1999

Changes in apoptotic and mitotic activity in rectal carcinoma after short-term cytostatic therapy as possible predictive factors.

Fifteen patients with rectal adenocarcinoma were endoscopically biopsied and given short-term [5 fluorouracil (5FU) (600 mg/m2) and Ca-Folinate (60 mg/m2) for two days] cytostatic therapy. Seven days later the tumor was resected or a second biopsy was performed. Apoptotic and mitotic indices were determined in the tumor tissue before and after the short-term chemotherapy. The patients were treated thereafter with long-term, intermittent 5 FU administration and followed up clinically for 4-13 months. Three patients showed progression of the disease, twelve improved or showed no tumor progression. An increase of the apoptotic index and decrease of the mitotic index after the short-term cytostatic treatment were seen in the tumor tissue of responder cases. Non-responders showed increase or no change in mitotic activity, and decrease or no change in apoptotic activity. These findings suggest that apoptotic and mitotic response to short-term cytostatic therapy may be additional predictive factor in rectal adenocarcinoma.

Adenocarcinoma↗
PubMed1998

[A new benzoquinone-containing antimetastatic product].

An orally applicable fermentation product of wheat germ containing 0.04% substituted benzoquinone (MSC) was invented by Hungarian chemists under the trade--name of AVEMAR. The following biological effects of this product were observed. Oral administration (3 g/kg body weight) of MSC enhances blastic transformation of splenic lymphocytes of mice. The same treatment shortens the survival time of skin grafts in co-isogenic mouse skin transplantation model, which points to immune-reconstructive effect of MSC. Highly significant anti-metastatic effect of MSC was observed in three metastasis models (3LL-HH, B16, HCR-25). The antimetastatic activity of MSC--besides the immune reconstitution--may also due to the cell-adhesion inhibitory, cell proliferation inhibitory, apoptosis-enhancing and antioxidant effects, which were also observed in our in vitro experiments. Based on the biological effects of MSC--which is non-toxic, according to subacute toxicology studies--this product may be used as an adjuvant in the therapy of malignant neoplasia and other diseases caused by or following immunedeprivation.

Administration, Oral↗
PubMed1998

The neuroprotective and neuronal rescue effects of (-)-deprenyl.

The pharmacological effects of (-)-deprenyl is multi-fold in its nature (dopamine sparing activity, neuroprotective and neuronal rescue effects), which cannot be explained solely by the irreversible MAO-B inhibitory action of the substance. Deprenyl slightly inhibits the re-uptake of noradrenaline and dopamine, but methylamphetamine, the metabolite of the inhibitor, by one order of magnitude is more potent in this respect, than the parent compound. Neither the metabolite nor (-)-deprenyl acts on the uptake of serotonin. The inhibitor has an intensive first pass metabolism after oral treatment. The in vivo pharmacokinetic studies with (-)-deprenyl, using the double labelled radioisotope technique (1.5 mg/kg; orally) in rats revealed that the molar concentration of methylamphetamine can reach the level suitable to induce a significant inhibition of amine uptake. Deprenyl, but especially methylamphetamine pre-treatment can prevent the noradrenaline release induced by the noradrenergic neurotoxin DSP-4. The uptake inhibitory effect of (-)-deprenyl and the metabolites is reversible. After repeated administration of (-)-deprenyl (1.5 mg/kg daily, for 8 days) sustained concentration of its metabolites was detected, compared to that of the acute studies. This can at least partly explain why (-)deprenyl should be administered daily to evoke therapeutic effects in Parkinson's disease. Administration of (-)-deprenyl in a low dose, following the toxic insult, can rescue the damaged neurones. The neuronal rescue effect of the drug was studied on M-1 human melanoma cells in tissue culture. The inhibitor reduced the apoptosis of serum-deprived M-1 cells, but the (+)-isomer failed to exert this effect. The (+/-)-desmethyl-deprenyl almost lacks the property to inhibit apoptosis. For neuroprotection and neuronal rescue an optimal dose of (-)-deprenyl should be administered, because to reach a well balanced concentration of the metabolites in tissues is critical.

Animals↗
PubMed1998

Apoptosis and p53 expression in human gliomas.

Twenty-five human gliomas of different histological grade and type were studied for p53 expression by immunohistochemistry and for apoptosis using ApopTag method. p53 expression (percentage of positive cells) was highest in anaplastic astrocytomas, followed by low grade astrocytomas and surprisingly in glioblastomas. Granular cytoplasmic p53 positivity appeared in 4/5 low grade oligodendroglioma and in 2/5 low grade mixed oligoastrocytomas. The means of apoptosis index in the different tumor types ranged between 0.8 and 11.5 with the highest values in anaplastic astrocytoma and glioblastomas. Although the number of cases per group were relatively low and the individual vales showed differences it seems that p53 expression is related to the biological aggressiveness of gliomas. It is also suggested that high level of apoptosis in malignant glioma could represent a p53 independent pathway.

Adult↗
PubMed1998

A new method to localize acid phosphatase using the confocal laser-scanning microscope.

The aim of the study was to work out a technique for the detection of acid phosphatase enzyme activity by confocal laser-scanning microscope using the histochemical acid phosphatase detection method (after Barka and Anderson 1962, modified by Bowen and Lewis 1985) routinely used for light microscopy. The density and the distribution of enzyme reaction product is dependent on the incubation time, as shown by different confocal images or ELISA reader. The inhibition of the enzyme activity with metal ions shows the same profile known from the literature. This staining method seems to be useful to demonstrate subcellular distribution of the enzyme in the lysosomes and in the Golgi apparatus.

Acid Phosphatase↗
PubMed1998

A somatostatin analogue induces translocation of Ku 86 autoantigen from the cytosol to the nucleus in colon tumour cells.

Flow cytometric and electron microscopic immunocytochemical studies have been performed in HT-29 human colon tumour cells in vitro, to determine and localise p86 Ku protein, which is a regulatory subunit of DNA-dependent kinase and a specific binding site for somatostatin. We have demonstrated that HT-29 cells contain p86 Ku and that the distribution between the cytoplasm and the nucleus is even. After administration of the somatostatin analogues Sandostatin and TT-232 to HT-29 cells, the p86 Ku content of the cytoplasmic compartment decreased in the first 4 h. An increase in the content of this protein in the nuclear compartment was observed at hour 1 followed by a decrease at hour 4 after treatment. Quantitative differences between the two analogues have been observed in this respect. The practical significance of these findings is discussed.

Antigens, Nuclear↗
PubMed1998

Coexpression of p53 and tissue transglutaminase genes in human normal and pathologic adrenal tissues.

The presence of p53 and tissue transglutaminase (tTG) gene expressions was investigated in human normal and pathologic adrenal tissues with two aims (1) to determine the tissue content of p53 protein, its messenger ribonucleic acid (mRNA) and, especially, tTG mRNA which has not been previously reported and (2) to study possible differences in the coexpression of p53 and tTG in various adrenal disorders. Using Northern blot analysis, p53 and tTG mRNAs were detected in each adrenal tissue examined including 5 normal human adrenals, 6 aldosterone-producing adenomas, 3 Cushing's adenomas, 1 primary nodular adrenocortical hyperplasia causing Cushing's syndrome in an infant, 12 non-hyperfunctioning adrenocortical adenomas, and 4 adrenocortical carcinomas. The results showed a significant positive correlation between these two mRNAs in all adrenal tissues except adrenocortical carcinomas. Compared to normal adrenals, high p53 mRNA levels were observed in aldosterone-producing and Cushing's adenomas and, most markedly, in a tissue from a primary nodular adrenocortical hyperplasia. Also, Cushing's adenomas had significantly higher tTG mRNA contents. Immunohistochemistry for wild-type and mutant p53 protein showed numerous p53 positive cells with a strong nuclear staining in a tissue from a primary nodular adrenocortical hyperplasia, whereas the p53 positive cells were absent, except those with a faint nuclear staining, in all other adrenal tissues. However, all adrenal tissues showed detectable p53 contents by the more sensitive method of luminometric immunoassay (LIA). Using this method, aldosterone-producing adenomas exhibited significantly higher p53 contents than normal adrenal tissues. These observations may support potentially important roles for p53 and tTG in adrenal pathophysiology, especially in mechanisms which influence the evolution and/or progression of aldosterone-producing and Cushing's adenomas and, most probably, hyperplasias.

Adrenal Gland Neoplasms↗
PubMed1998

Experimental and human liver fibrogenesis.

In this work, we provide an overview of our results obtained by studying the role of transforming growth factor beta1 and proteoglycans in liver fibrogenesis. It has been found that transforming growth factor beta1 is one of the most important stimulators of extracellular matrix synthesis in the liver. In chronic liver injury, desmin-positive non-parenchymal liver cells expressed transforming growth factor beta1. The extracellular localization of the growth factor correlated well with types I, III and IV procollagen-alpha, which were detected in the fibrous septa of chronically injured livers. A similar distribution pattern was observed in human specimens. To identify the role of transforming growth factor beta1 in liver extracellular matrix protein synthesis, transforming growth factor beta1-positive transgenic mice were generated. Animals expressing the growth factor in their liver showed spontaneous liver fibrosis. Proteoglycans also participate in fibrogenesis. The majority of liver-specific heparan sulfate proteoglycans, such as syndecan-1 and fibroglycan, are produced by hepatocytes. The extracellular matrix proteoglycans decorin and perlecan are synthesized by non-parenchymal liver cells. The amount of the latter is very low in normal liver, but increases dramatically in liver fibrosis. The effect of regulatory factors on liver proteoglycans seems to be cell type-specific. In contrast to previous observations, elevated amounts of decorin did not inhibit the action of transforming growth factor beta1 in the liver.

Animals↗
PubMed1998

Formaldehyde cycle and the natural formaldehyde generators and capturers.

S-adenosyl-L-methionine serves as a methyl donor in virtually all of the vast number of enzymatic transmethylation reactions including DNA methylation. On the basis of our former experiences we questioned the formation of a methyl cation or methyl radical in the enzymatic transmethylation reactions. The formation of formaldehyde from the methyl moiety of S-adenosyl-L-methionine has been demonstrated. It became increasingly evident that there is a formaldehyde cycle in biological systems in which the formation of the methyl group of L-methionine takes place through formaldehyde and the formation of formaldehyde from S-adenosyl-L-methionine is linked to different enzymatic transmethylation reactions. It is also known that during demethylation processes both formaldehyde and demethylated compound can be formed. The abnormalities of the originally controlled formaldehyde cycle and the uncontrolled enzymatic production of formaldehyde from endogenous and/or exogenous substrates may be potential risk factors in pathogenesis of different disorders. The formaldehyde generator and capturer molecules may potentially normalise these abnormal processes. Trans-resveratrol (trans-3,5,4'-trihydroxystilbene), which is as phytoalexin, occurs naturally in grapes and a variety of medicinal plants. According to our present observations it is a natural concentration-dependent formaldehyde capture molecule. It would seem that elimination of the uncontrolled formaldehyde with resveratrol may exert a double effect in biological systems. The elimination of formaldehyde with resveratrol (first step) may cause a cardioprotective effect and the reaction products between resveratrol and formaldehyde (second step) may act as a chemopreventive factor against cancer.

Formaldehyde↗
PubMed1998

Determination of endogenous formaldehyde in plants (fruits) bound to L-arginine and its relation to the folate cycle, photosynthesis and apoptosis.

A very powerful nucleophilic reagent, hydralazine(1-hydrazino-phtalazine) proved to be suitable for determination of the endogenous formaldehyde level in biological samples. It was found that in different plants (vegetables, fruits, especially in red beet, cauliflower, kohlrabi, grapes) is a large amount of releasable endogenous formaldehyde (0.5-1.0 mM) bound to L-arginine mainly in the form of N(G)-trihydroxymethyl-L-arginine (TriHMA). N(G)-hydroxymethyl-L-arginines (HMA) were proved to transfer their hydroxymethyl groups to tetrahydrofolic acid producing N5,N10-methylene-tetrahydrofolate, the coenzyme of thymidylate synthase. HMA was found to inhibit the cell proliferation of HT-29 cell culture (human colon adenocarcinoma ATCC HT-B 38) causing apoptosis. Photosynthetic experiments produced confirmatory evidences that 14CH2O could be formed in photosynthesis already after 10 seconds of 14CO2 fixation in the seedlings of Zea mays L. (single cross) and the 14CH2O was immediately trapped by L-arginine mainly as TriHMA.

Adenocarcinoma↗