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Biomedical subjects

B Szende

Publications and source records attributed to B Szende.

At least 73 records · Page 4Linked to original sources

Formaldehyde generators and capturers as influencing factors of mitotic and apoptotic processes.

There is a growing amount of evidence pointing to the fact that several endogenous and exogenous methylated compounds are potential formaldehyde generators in their biological reactions. N(G)-methylated lysines, N(G)-methylated as well as hydroxymethylated arginines, and 1'-methyl-ascorbigen have been examined in this respect. The apoptosis-inducing effect of formaldehyde molecules formed from methyl groups was earlier first published by our group. Dimedone, an artificial capturer molecule for formaldehyde, has been found to prevent the apoptosis-inducing effect of 1'-methyl-ascorbigen as well as N(G)-hydroxymethylated arginines. More recently resveratrol, present in grapes and wines, has been shown to have cardioprotective and cancer chemopreventive effect. Our group has been successful in demonstrating that this natural formaldehyde capturer molecule can also influence cell proliferation and apoptosis. The apoptosis-inducing or -preventing effect of formaldehyde generators and capturers seems to be dose-dependent and may be utilized in various disturbances of cell proliferation and active cell death.

Apoptosis↗

Reduction of apoptosis of in vitro cultured lymphocytes of HIV-positive persons by N(G)-hydroxy-methylated-L-arginine and 1'-methyl-ascorbigen.

Some formaldehyde generating chemicals due to reduction of apoptosis in lymphocytes may slow down the progress of immune decline of HIV-infected individuals. N(G)-hydroxy-methylated-L-arginine (MAX) and 1'-methyl-ascorbigen (MeAsc) could enter this way the biochemical pathway of cells and affect the apoptotic process. Separated peripheral blood lymphocytes of five asymptomatic HIV-positive persons were cultured. Unstimulated, IL-2 stimulated and IL-2 stimulated plus 0.1, 1.0, 10.0 microg/ml MAX or MeAsc treated lymphocytes were investigated for apoptosis morphologically (HE) and by flow cytometrical DNA fragmentation method. IL-2 stimulation lowered the apoptotic rate in lymphocytes of HIV-positive persons related to unstimulated ones. MAX and MeAsc reduced the apoptotic activity of stimulated lymphocytes in the least or the middle doses while in the higher dose did not. MAX and MeAsc reduced the apoptotic activity of stimulated lymphocytes originated from HIV-positive patients in vitro. This compounds may have the same effect in vivo and may prolong the symptomless period of HIV-infected patients. The role of methylation and production of formaldehyde in this process is discussed.

Apoptosis↗

Apoptosis and acute lymphocytic leukemia in children.

We examined in vivo spontaneous and prednisolone-induced apoptosis in peripheral blood samples of 23 children with ALL by flow cytometric and morphologic methods. There was no significant spontaneous apoptosis before the therapy. Six hours after prednisolone therapy, increased apoptosis was found in 19 of 23 cases. In one case, the apoptosis of blast cells could not be compared with the clinical data, because the patient died in sepsis during the induction therapy. In 18 of 22 evaluable cases, the in vivo apoptosis correlated with the decrease of leukemic blasts during the first 8 days of prednisolone monotherapy. In 20 of 22 children, a correlation was found between in vivo prednisolone-induced apoptosis and clinical outcome. The p53 gene expression was elevated in 2 of 10 patients. No elevation in the expression of bcl-2 gene was observed. In 6 of 23 cases, the glucocorticoid receptors were measured. The correlation of clinical responsiveness and gcR mRNA shows less parallelism than does the apoptosis correlation.

Adolescent↗

Structure determination and synthesis of lysine isopeptides influencing on cell proliferation.

The clavicepamines are lysine-rich basic proteins isolated from saprophytic culture of ergot (Claviceps purpurea), having human pharmacological importance. Based on structure determinations, it was demonstrated that the epsilon-lysine (poly)peptides are the fundamental structural units of clavicepamines. To study the relationship between chemical structure and biological effect, solution and solid-phase synthesis of lysine isopeptides were performed. Poly-epsilon-lysines were synthesized with polycondensation via application of p-nitrophenylester temporarily protecting groups together with simultaneous activation. The biological investigations of poly-epsilon-lysines showed a cell-proliferation retarding effect, so they inhibit growth of some animal tumors, practically without toxic side effects.

Antineoplastic Agents↗

Increased apoptosis of adult rat lymphocytes after single neonatal vitamin A treatment (hormonal imprinting). A flow cytometric analysis.

Newborn rats were treated with a single dose of vitamin A (retinol) and apoptosis of peripheral lymphocytes was studied by flow cytometry in adult age. Vitamin A treatment (hormonal imprinting) caused a moderate, however significant elevation in the number of apoptotic lymphocytes after three months. Dexamethasone or Concanavalin-A alone did not influence apoptosis significantly. However, in the neonatally retinol treated rats dexamathasone significantly elevated the quantity of apoptotic lymphocytes related to the control or Concanavalin-A treated control cells. The results call attention to the prolonged effect of hormonal imprinting in a new index and to the possible dangerous effects in human, neonatally treated with vitamin A.

Animals↗

Multifocal hemangioendothelioma of the fetus and placenta.

A case of multifocal hemangioendothelioma of the liver, adrenal gland, and placenta is reported. The histological appearance of the tumor is consistent with an infantile hemangioendothelioma, type 2. Multifocal development is the most obvious explanation for the disease but the possibility that this represents malignant placental neoplasm with metastases requires consideration.

Adrenal Gland Neoplasms↗

Search for prognostic factors in head and neck cancer.

Fifteen patients with head and neck carcinoma were treated with irradiation (14-70 Gy telecobalt). Apoptotic and mitotic index, DNA index, ratio of cells in S phase, p53 protein overexpression in untreated tumours as well as the changes of these parameters after the first 2 Gy irradiation except proliferative kinetics parameters were examined in order to determine the prognostic value of these factors. The data show that inducibility of apoptosis is very low in head and neck carcinomas which correlate with the unfavourable prognosis. The decrease in mitotic index after the first 2 Gy irradiation, which occurred in 7 cases--5 of them still alive--indicates a better chance for relatively longer survival. In immunohistochemically p53 positive tumours frequently occurring aneuploidy and elevated S-phase rate were found.

Adult↗

Clinicopathologic aspects of 8 Kaposi's sarcomas among 1009 renal transplant patients.

In 8 of 1009 patients receiving renal grafts and consecutive immunosuppressive therapy during the last 20 years in Budapest, Hungary, Kaposi's sarcoma developed 6.5 months (average) after transplantation. Of 8 cutaneous cases of this disease, 5 also presented visceral manifestations. Seven patients died. Those with visceral tumors died because of the tumor itself. One patient affected by cutaneous tumor has survived for 5 years post-treatment. The relatively high incidence of Kaposi's sarcoma may be explained by a high infection rate with Herpes virus 8, which was shown to be positive in all three cases investigated.

Adult↗

A tumor-selective somatostatin analog (TT-232) with strong in vitro and in vivo antitumor activity.

We report a series of new in vitro and in vivo data proving the selective antitumor activity of our somatostatin structural derivative, TT-232. In vitro, it inhibited the proliferation of 20 different human tumor cell lines in the range of 50-95% and induced a very strong apoptosis. In vivo TT-232 was effective on transplanted animal tumors (Colon 26, B16 melanoma, and S180 sarcoma) and on human tumor xenografts. Treatment of MDA-MB-231 human breast cancer xenografted in mice with low submaximal doses of TT-232 [0.25 and 0.5 mg/kg of body weight (b.w.)] caused an average 80% decrease in the tumor volume resulting in 30% tumor-free animals surviving for longer than 200 days. Treatment of prostate tumor (PC-3) xenografted animals with 20 mg/kg of b.w. of TT-232 for 3 weeks resulted in 60% decrease in tumor volume and 100% survival even after 60 days, while 80% of nontreated animals perished. We have demonstrated that TT-232 did not bind to the membrane preparation of rat pituitary and cortex and had no antisecretory activity. TT-232 was not toxic at a dose of 120 mg/kg of b.w. in mice. Long-term incubation (24 h) of tumor cells with TT-232 caused significant inhibition of tyrosine kinases in good correlation with the apoptosis-inducing effect. The level of p53 or KU86 did not change following TT-232 treatment, suggesting a p53-independent apoptotic effect. Preincubation of human breast cancer cells (MDA-MB-453) with TT-232 for 2 h decreased the growth factor receptor autophosphorylation. All of these data suggest that TT-232 is a promising and selective antitumor agent.

Animals↗

[Support by telecommunication of decisions in diagnostic pathology. Experience with the first telepathology system in Hungary].

The term of telepathology can be determined as diagnostic work of the pathologist at distance via an interactive telecommunication connection in which the image of the specimen appears on a monitor instead of viewing it directly through a microscope. Being a part of the telemedicine, the fast development of the telepathology is based on the revolution of the new digital technology. Technical advances of telecommunication and of image procession in the latest 80s have provided the means to transfer huge amount of visual information in narrow communication bandwidth in two direction link. In 1995 multiple live image transmission with simultaneous voice transfer has been performed between the Department of Pathology of MI Central Hospital and 1.st Institute of Pathology and Experimental Cancer Research of Semmelweis Medical University, Budapest. Transfer rate via ISDN channel was 128 kbit/sec. The first live image telemedicine system in CCE/NIS countries has achieved transmission of cytological smears, frozen sections and paraffin embedded slides supplemented with immunohistochemical preparations. Quality of visual information using video-conference software of standard H.320 was suitable for diagnosis. Development of global telepathology services depends on compatibility of different systems and on comprehensive examinations of cost, accessibility and quality for the clients and providers of telemedicine. Recent paper surveys shortly the historical development of the telepathology, analyses the essence of the new consultation technology, summaries the first experiences in Hungary and raises some questions have to be answered in the near future.

Academies and Institutes↗

[Experiences with a new vacuum-accelerated microwave histoprocessor].

Methods of microwave and vacuum accelerated fixation, dehydration and paraffin embedding are described. They can be carried out in a new type of vacuum and temperature stabilizable microwave histoprocessor: MFX-800. The whole histoprocessing lasts 3.5-5.5 hours depending on the thickness of the tissue blocks. Preserved structural detail, intensive staining and good antigen preservation were achieved with various tissues. This new histoprocessing facility can be highly recommended for pathology laboratories interested in speeding up the processing procedure, as well as in immunohistochemistry.

Equipment Design↗

Working experience with a new vacuum-accelerated microwave histoprocessor.

Methods of microwave and vacuum-accelerated fixation, dehydration, and paraffin embedding are described, using a new type of vacuum and temperature stabilizable microwave histoprocessor: MFX-800. The whole histoprocessing cycle lasts 3.5-5.5 h, depending on the thickness of the tissue blocks. Well-preserved structural detail, intense staining, and good antigen preservation were achieved with various tissues. This new histoprocessing facility is recommended for routine pathology laboratories in speeding up their processing procedures.

Decalcification Technique↗

The pharmacology of B-type selective monoamine oxidase inhibitors; milestones in (-)-deprenyl research.

(-)-deprenyl cannot be considered as a simple, selective inhibitor of MAO-B. It increases the dopaminergic tone in the central nervous system by a complex mechanism. The MAO-B inhibition could result in a potentiation of the effect and the reduction of the dose of L-dopa, including the restoration of the sensitivity to L-dopa treatment, when the response to the drug has already been diminished or lost. Pre-treatment with (-)-deprenyl prevent the effect of neurotoxins like MPTP, 6-hydroxydopamine, DSP-4, AF64A by inhibiting the conversion of the pretoxin to toxin, or by inhibiting the neuronal reuptake mechanisms, or the combination of the two processes. However, other effects of the inhibitor cannot be ruled out. (-)-deprenyl, but not its (+)-enantiomer, proved to be a potent inhibitor of programmed cell death (apoptosis) of PC12 cells and that of human melanoma cells, in a concentration which does not induce MAO-B inhibition. The activity of MAO-B increases with age and the age related changes led to an overproduction of neurotoxic agents. The inhibition of the enzyme activity can play a preventive role against neurodegenerative brain disorders. The most widely used MAO-B inhibitor in the therapy is (-)-deprenyl and it lacks the "cheese reaction". The complex mechanism for the lack of the former effect is not fully known.

Age Factors↗

Accuracy of admission and clinical diagnosis of tumours as revealed by 2000 autopsies.

Admission, clinical and autopsy diagnoses of tumour were computed in 2000 consecutive cases, aged 30-80 years, using data collected in two university pathology departments in Budapest, Hungary. Based on diagnosis of tumour, regardless of site, as the underlying cause of death false-negative rates were 37.4% at admission and 8.8% clinically. Corresponding false-positive rates were 8.4 and 9.1%. General practitioners who correctly diagnosed a tumour as the cause of the terminal illness identified the primary site wrongly in 20.6% (90/436) of cases. Hospital clinicians did so in 20.4% (130/636) of cases. Overall, of site-specific tumours considered as the underlying cause of death at autopsy, 27.4% were incorrectly diagnosed clinically and 50.4% at admission. Diagnostic errors were particularly common for tumours of the lung, liver, ovary and gall bladder. Graduate and postgraduate education, planning of the health care system and quality of cancer care may benefit from statistical data derived from autopsy diagnoses.

Adult↗

Granulomatous hypophysitis associated with Takayasu's disease.

We report a case of Takayasu's disease, presenting with symptoms of fever, anaemia, elevated erythrocyte sedimentation rate, anterior pituitary failure and mild diabetes insipidus. A pituitary mass with suprasellar extension mimicking a pituitary adenoma was found, and histological examination revealed granulomatous hypophysitis. The diagnosis of Takayasu's disease was established after the development of a multiple arterial occlusive disease. We suggest that Takayasu's disease should be considered in the differential diagnosis of granulomatous hypophysitis of unknown origin.

Blood Sedimentation↗

Misdiagnosis of lung cancer in a 2000 consecutive autopsy study in Budapest.

OBJECTIVE: To determine the accuracy of lung cancer mortality data based on clinical observations in the absence of autopsy and to identify factors affecting the accuracy of diagnosis. METHODS: Admission, pre-autopsy and post-autopsy diagnoses were recorded for 1000 consecutive autopsies in each of two University departments in Budapest with high autopsy rates for persons dying in hospital. In those 87 cases where one or more diagnosis included primary lung cancer, additional data were collected concerning clinical investigations relevant to the diagnosis and the histological type lung cancer, and on smoking habits. RESULTS: 59% (36/61) of lung cancers seen at autopsy were not detected pre-autopsy, while 50% (25/50) of those diagnosed pre-autopsy were not confirmed at autopsy. Many misdiagnoses arose because patients were too ill to be properly investigated and/or died before investigations could be completed. Accuracy of diagnosis increased with the number of diagnostic techniques applied, but was still far from perfect in the absence of necropsy. Underdiagnosis was commoner in non-smokers and overdiagnosis commoner in smokers. CONCLUSIONS: Without necropsy, lung cancer misdiagnosis is common, especially when modern diagnostic procedures cannot be fully employed. Knowledge of smoking habits may affect diagnostic accuracy.

Adult↗