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Biomedical subjects

I Juhász

Publications and source records attributed to I Juhász.

At least 19 recordsLinked to original sources
PubMed2004

Opposite roles of protein kinase C isoforms in proliferation, differentiation, apoptosis, and tumorigenicity of human HaCaT keratinocytes.

We have previously shown that the protein kinase C (PKC) system plays a pivotal role in regulation of proliferation and differentiation of the human keratinocyte line HaCaT which is often used to assess processes of immortalization, transformation, and tumorigenesis in human skin. In this paper, using pharmacological and molecular biology approaches, we investigated the isoform-specific roles of certain PKC isoenzymes (conventional cPKCalpha and beta; novel nPKCdelta and epsilon) in the regulation of various keratinocyte functions. cPKCalpha and nPKCdelta stimulated cellular differentiation and increased susceptibility of cells to actions of inducers of apoptosis, and they markedly inhibited cellular proliferation and tumor growth in immunodeficient mice. In marked contrast, cPKCbeta and nPKCepsilon increased both in vitro and in vivo growth of cells and inhibited differentiation and apoptosis. Our data present clear evidence for the specific, antagonistic roles of certain cPKC and nPKC isoforms in regulating the above processes in human HaCaT keratinocytes.

Animals↗
PubMed2002

Cimetidine and a tamoxifen derivate reduce tumour formation in SCID mice xenotransplanted with a human melanoma cell line.

Histamine is produced by many cells expressing histidine decarboxylase (HDC), the enzyme responsible for the synthesis of histamine. Since melanoma cells and tissue contain relatively large amounts of histamine, the functional significance of histamine was examined using specific antihistamines in vitro and in vivo in the human melanoma cell line HT168 and severe combined immunodeficiency (SCID) mice. It was shown that the H2 receptor antagonist cimetidine when combined with N, N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine-HCl (DPPE), a tamoxifen derivate, inhibits the proliferation of HT168 cells. Furthermore, it is suggested that there is a factor(s) that interferes with the exponential growth of HT168 cells xenografted to immunodeficient mice, and cimetidine and DPPE together significantly influence this factor(s). This combination of antihistamines also increases the survival of human melanoma-grafted mice. These changes are accompanied by enhanced infiltration of interferon-gamma- producing mouse macrophages into the tumour tissue. These findings suggest that two different mechanisms are probably acting concordantly: direct inhibition of tumour cell proliferation by the H2 receptor antagonists, and activation of the local immune response characterized by interferon-gamma production. These findings may help to elucidate the possibility of a rationally designed antihistamine strategy in melanoma therapy.

Animals↗
PubMed1998

Studies on the tissue-related phenotypic heterogeneity of murine B cells.

The development of B cells is accompanied by their ability to specifically enter the peripheral lymphoid tissues. Recently, we described a novel rat monoclonal antibody (IBL-2; IgG2b/kappa) reacting with a 26/29-kD heterodimeric structure of the cell surface. This mAb has been found to recognize differentially the peripheral B cells of mice depending on their tissue origin. The majority of splenic B cells as well as the mature B cells in the bone marrow were stained with this mAb, whereas the B lymphocytes isolated from LN or Peyer's patches displayed only negligible reactivity. We extended these observations by analyzing the relationship between the expression of IBL-2 antigen and L-selection on the surface of B-cell precursors in the bone marrow by multiparameter flow cytometry. Within the B220 positive compartment, a significant difference of L-selectin expression could be observed between the various IBL-2-reactive subsets. Furthermore, we investigated whether evidences for the establishment of tissue-associated phenotypic heterogeneity similar to that found in normal mice could be found upon the adoptive transfer of normal unselected splenic lymphocytes into SCID recipients (Spl-SCID). It has been found that a large part of the splenic B cells preserved their IBL-2 reactivity, whereas the LN B cells had lost the IBL-2 antigen in Spl-SCID. These data indicate that the phenotypic difference within the SCID mice may be the result of the migration of B lymphocytes from the spleen toward the lymph nodes, and the altered expression of the IBL-2 antigen correlates with this process.

Adoptive Transfer↗
PubMed1996

Repopulation of Langerhans cells during wound healing in an experimental human skin/SCID mouse model.

The epidermal repopulation of Langerhans cells (LCs) during wound healing was examined using a human skin severe combined immunodeficient (SCID) mouse model. The experiments, were carried out after proving the human origin of keratinocytes repopulating the wound beds using the W6/32 monoclonal antibody. It was shown that CD1a- and HLA-DR-positive dendritic cells (mostly LCs) are already detectable 2 days after injury within the newly formed epithelium. In the excisional wounds investigated, neither HLA-DR nor ICAM-1 expression of human keratinocytes was observed. Our present data suggest that LC repopulation is an early event in the process of re-epithelization.

Animals↗
PubMed1996

Thrombospondin receptor (CD36) expression of human keratinocytes during wound healing in a SCID mouse/human skin repair model.

Using a human skin/severe combined immunodeficient (SCID) chimeric mouse model, we examined the keratinocyte expression of the thrombospondin receptor (CD36) and its ligand thrombospondin-1 (TSP1) in acute uninflamed wounds. Positive suprabasal keratinocyte expression of CD36 was observed as early as 30 minutes after wounding in the adjacent, intact epidermis; it disappeared 4 days later. Keratinocytes of the freshly re-epithelised wounds and those of the surrounding epidermis remained TSP1-negative throughout the whole observation period of 7 days. Our results indicate that CD36-positive keratinocytes, probably in connection with activated, TSP1-positive thrombocytes, may play an important role in the early phase of wound healing.

Animals↗
PubMed1993

TxA2-PGI2-PGF2 alfa responses in the kidney to blood pressure reduction induced by vasodilator/vasorelaxing agents with different action in patients with essential hypertension.

In blood pressure (BP) reduction induced by gallopamil, hydralazine and prazosin in patients with essential hypertension a common trend was found in renal prostanoid production which included increased TxB2 excretion and/or augmented TxB2/6-keto-PGF1alfa ratio and, with the exception of response to prazosin, enhanced PGF2alfa excretion. Role of direct biochemical actions by the drugs in these responses was excluded by in vitro experiments with kidney slices from rats. The clinical and in vitro experimental findings suggested a mediator role of sympathetic activation but not that of the increased renin release in the urinary eicosanoid responses. Significant correlation was observed between the changes in reabsorbed amounts of sodium and excreted amounts of TxB2 and PGF2alfa. The results suggest that the reactivity of pressure type prostanoids in the kidney could be considered as part of a more complex renal counteraction to BP decrease.

Adolescent↗
PubMed1993

[Traumatic hip dislocation in childhood].

Authors describe the diagnostic and therapeutic problems of the traumatic dislocation of the hip in children and report on the experiences of their 8 cases. It is stressed that the condition of the good result in the early diagnosis and reduction. For the recognition and treatment of the late complications a 1.5-2 years follow-up of the patients is thought to be important.

Accidental Falls↗
PubMed1991

Role of endothelium, oxygen and ionic milieu in the prostacyclin and thromboxane production of rat aortic tissue slices.

The present study was executed in order to get further data on the role of vessel wall constituents in prostanoid synthesis and on the effect of anorganic constituents on it. Prostacyclin and tromboxane production of rat aortic tissue slices with intact endothelium and after mechanical as well as chemical endothelium removal were studied. The effects of hypoxia and changes in the ionic milieu on the release of these prostanoids were also examined. The tissue slices were incubated in normal or in modified Krebs-Ringer solution, bubbled with 95% O2 and 5% CO2 (with the exception of the studies in hypoxic conditions). Prostacyclin and thromboxane release was determined by specific radioimmunoassay of the stable metabolites, 6-keto-PGF1 alpha and TxB2, from the incubation medium. 174 tissue samples obtained from 164 rats were studied. Mechanical removal of the endothelium increased prostacyclin production of the aortic segments about fivefolds from a basal rate of 52.9 +/- 19.4 ng/gr/min, while it had no significant effect on thromboxane release (basal rate 0.83 +/- 0.13 ng/gr/min). Treating the endothelium with 1.0 M HCl almost totally suppressed prostacyclin release. Lowering the partial oxygen tension of the incubation medium significantly decreased the production of prostacyclin, while release of TxB2 somewhat increased. Increasing the Ca2+ concentration of the medium between 0-5 mM the release of prostacyclin was augmented and the release of thromboxane was diminished. Potassium free medium caused a very large increase in prostacyclin release of the tissue slices. The results show that release of vasoactive prostanoids from isolated rat aortic wall is dependent not exclusively on the endothelium and that various methods of endothelium removal may have distinct influences on prostacyclin and thromboxane productions. The changes in anorganic constituents of the surrounding medium could massively affect prostacyclin and thromboxane production of rat aortic tissue. The alternative effects of the above listed treatments on the release of prostacyclin and thromboxane from the rat aortic wall suggest the existence of different mechanisms in the control of the production of the two major prostanoids possessing opposite physiological effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Relation of renal thromboxane A2 production to urine flow, electrolyte excretion and plasma renin activity in control state and drug induced hypotension.

The functional importance of renal TxB2 generation in the maintenance of elevated arterial blood pressure in essential hypertension was followed in 22 patients, using the method of sustained blood pressure decrease by i.v. sodium nitroprusside infusion. Linear correlation between urinary excretion of TxB2, urine flow, and sodium excretion could be established in both control and hypotensive periods. Presumably, changes in urinary excretion of TxB2 reflect a secondary intrarenal counterregulatory response.

Adult↗
PubMed1988

Prostanoid response in the kidney of hypertensive subjects as part of renal counteraction to gallopamil-induced blood pressure decrease.

The purpose of the study was to characterize the renal TxA2, PGI2 and PGF2 alpha release in response to arterial blood pressure (BP) fall induced by systemic and intrarenal vasorelaxation in subjects with essential hypertension. Significantly enhanced TxB2- and PGF2 alpha excretion and no change in ratio TxB2/6-keto-PGF1 alpha were found in urine in hypertensive patients after administration of the Ca++ entry blocker gallopamil, used to induce BP fall. This response was associated with significant PRA elevation in peripheral venous samples. In in vitro experiments, direct and indirect effects of gallopamil on renal tissue could be distinguished. Gallopamil resulted in significant diminution of TxA2 production and a decrease in TxB2/6-keto PGF1 alpha ratio in incubated rat kidney slices. This model was also used to test biochemically the effect of reflex sympathetic activation on prostanoid generation in kidney. It was concluded that this mechanism was only one among the indirect mechanisms by which gallopamil could induce that renal prostanoid response in hypertensive subjects. The response in urinary TxB2- and PGF2 alpha excretion was found to be significantly related to the changes in sodium reabsorption. These results suggested, that the increase in renal TxA2 and PGF2 alpha production in response to systemic and intrarenal "vasodilation" induced by gallopamil in hypertensive subjects can be interpreted as part of counteraction of the kidneys to BP fall.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Surface markers of blood lymphocytes in bronchial carcinoma.

The proportion of autologous rosette-forming, i.e. autoerythrocyte-binding, T-lymphocytes, was studied in 34 patients with untreated, operable bronchial carcinoma. The number of autorosettes in patients with bronchial carcinoma was considerably below the mean value for the normal control group. In patients with metastatic involvement of the regional lymph nodes at the time of surgery the reduction in the number of autorosettes was still more marked. On the 10th postoperative day after resection of the tumour and in case of remission five months after surgery, the number of autorosettes showed a significant rise approximating the normal value. The distribution of sheep-E-rosette-forming and of the "active-early" T-lymphocytes was also studied. On the evidence of the results, the number of autorosette-forming lymphocytes lends itself to a follow-up of bronchial carcinoma by early demonstration of remissions or recurrences.

Adult↗
PubMed1983

Diurnal rhythm of beta endorphin in normotensive and hypertensive patients: the effect of clonidine.

Diurnal rhythm of plasma beta endorphin was established with the highest level in the morning and the lowest one at midnight in normotensive subjects and also in patients with essential hypertension. Clonidine (300 micrograms daily) significantly increased plasma beta endorphin concentrations only in the hypertensive patients. The significant linear correlation between the increase in plasma beta endorphin concentration and the decrease in blood pressure (both systolic and diastolic) in these patients may point to the role of this endogenous opioid in the antihypertensive action of clonidine.

Circadian Rhythm↗