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Biomedical subjects

J Szalay

Publications and source records attributed to J Szalay.

At least 19 recordsLinked to original sources

Association of elevated serum heat-shock protein 70 concentration with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia: a case-control study.

Our aim was to investigate the association between serum heat-shock protein (Hsp) 70 concentration and hypertensive disorders of pregnancy. One hundred and forty-two pregnant women with hypertensive disorders (93 with preeclampsia, 29 with transient hypertension of pregnancy and 20 with superimposed preeclampsia) and 127 normotensive, healthy pregnant women were included in the study. Serum Hsp70 concentration was measured using enzyme-linked immunosorbent assay. The serum Hsp70 concentration was significantly higher in patients with transient hypertension of pregnancy, in preeclamptic patients and in patients with superimposed preeclampsia than in the control group (median (25-75 percentile): 0.66 (0.52-0.84), 0.55 (0.42-0.80), 0.61 (0.42-0.91) ng/ml vs 0.31 (0.27-0.39) ng/ml, respectively; P<0.001). Multivariate logistic regression analysis showed independent association of elevated serum Hsp70 level with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia. The difference in serum Hsp70 concentration between preeclamptic patients and the control group was statistically significant in each gestational age category. In the groups of preeclamptic and superimposed preeclamptic patients, there was no significant difference in serum Hsp70 concentration between mild and severe preeclamptic patients, between patients with late and early onset of the disease, as well as between preeclamptic patients without and with foetal growth restriction. In conclusion, serum Hsp70 concentration is elevated in transient hypertension of pregnancy, in preeclampsia and in superimposed preeclampsia. Circulating Hsp70 may not only be a marker for these conditions, but might also play a role in their pathogenesis. However, further studies are needed to explore its role in the pathogenesis of hypertensive disorders of pregnancy.

Adult↗

Associations of PKC isoforms with the cytoskeleton of B16F10 melanoma cells.

Although PKC plays a major role in regulating the morphology and function of the cytoskeleton, little is known about in situ associations of specific isoforms with the cytoskeleton. We demonstrate that seven PKC isoforms are expressed in B16F10 melanoma cells and show different levels of induction by serum. Using cell cytoskeleton preparations (CSKs), confocal microscopy, and immunocytochemistry, all isoforms show specific patterns of localization to focal contact-like structures (alpha, delta), very small cytoplasmic granules/vesicles (all isoforms), dense ordered arrays of small granules in the perinuclear region (alpha, delta), granules/vesicles associated with a homogeneous framework in the cytoplasm adjacent to the nucleus (gamma), or irregular-shaped patches of granules at or near the nuclear perimeter (eta, theta). In addition, several isoforms are present as cytoplasmic granules/ vesicles in linear or curvilinear arrays (alpha, delta, epsilon, theta). When isoform localization is examined using 3.7% formaldehyde or methanol:acetone, the patterns of localization in CSKs are often difficult or impossible to detect, and many are described here for the first time. Double-labeling experiments with CSK demonstrate that PKC actin co-localizes with punctate alpha-rich particles above the nucleus, granules of epsilon throughout the cytoplasm, and with theta in irregular-shaped aggregates associated with the nucleus. Vimentin co-localizes with perinuclear granules of delta and beta(2), and alpha-tubulin co-localizes with theta in structures at or near the nuclear surface and in microtubules associated with the microtubule organizing center (MTOC). In summary, the present study demonstrates that seven PKC isoforms are endogenously expressed in B16F10 melanoma cells. These isoforms show various levels of induction by serum and specific patterns of association with various components of the detergent-resistant cell cytoskeleton.

Acetone↗

[Significance of the determination of estrogen and progesterone receptors in trophoblast diseases].

Binding capacity (Bmax) and affinity (Kd) of cytoplasmatic estradiol and progesteron receptors were determined in trophoblastic tissue and in decidual endometrium by the authors. Results in normal and pathological endometrium and in mature placenta tissue were compared. Both estrogen and progesteron receptors were proved to exist in the decidual endometrium nearest to the molar tissue. Their binding parameters are similar to those in normal endometrium. No progesterone receptors were found in the molar tissue. Binding capacity of estrogens were found to be similar to that of the normal mature placenta. The lack of progesterone receptors might be an etiological factor in the pathogenesis of trophoblast diseases.

Abortion, Spontaneous↗

Regulation of the metastasis of murine ocular melanoma by natural killer cells.

In the current study we examine parameters affecting the metastasis of ocular tumors of in vivo derived B16F10 melanoma. In C57BL/6J beige (bg/bg) mice, with low NK activity, metastasis to the lungs was increased and survival time decreased. In C57BL/6J normal (+/+) mice treatment with PK136, a highly specific monoclonal anti-NK antibody (Ab), caused a depletion of NK cytotoxic activity, as demonstrated using a standard 51Cr release assay. In animals bearing ocular tumors, treatment with PK136 Ab resulted in significantly increased pulmonary metastasis and an altered pattern of metastasis. The effect of combined treatment protocols using LS2616 (linomide) and cyclophosphamide (Cy) was examined in enucleated and unenucleated animals. Treatment with LS2616 and Cy resulted in a significant decrease in mean pulmonary metastases (MPM), a decreased frequency of metastasis to the submandibular lymph nodes and an increase in mean survival time. In enucleated mice this combined treatment protocol resulted in apparent cures, the lowest MPM and the longest survival time observed. When tumor-bearing mice were treated with either silica, carrageenan or sublethal gamma irradiation, no effect on metastasis or survival was observed. This study demonstrates the importance of the NK cell as a primary effector cell for the control of metastasis from in vivo derived ocular B16F10 melanoma.

Adjuvants, Immunologic↗

A treatment for metastasis of murine ocular melanoma.

In experiments using cultured cells, LS2616 has been shown to decrease growth of primary tumors and pulmonary metastasis of murine melanoma. In the current study, we examine the efficacy of LS2616 for the prophylactic and therapeutic treatment of metastases from ocular and flank inoculations of the highly aggressive in vivo derived B16F10 melanoma in C57BL/6J mice. Experimental animals were treated with 160 mg/kg/day of this drug in drinking water, until they became moribund or died. When mice were pretreated for 7 days and inoculated subcutaneously (sc) or intracamerally (ic) with 10(5) in vivo derived B16F10 tumor cells, the mean number of pulmonary metastases was significantly reduced, and the incidence of pulmonary metastases decreased. In ocular experiments, when pretreatment with drug was combined with enucleation at day 7, the mean number of lung nodules was significantly reduced, the incidence of metastasis to the lung and lymph nodes decreased and survival increased. An apparent cure rate of 31% was observed. Treatment beginning on the day of enucleation (day 7) resulted in a reduction of pulmonary metastases, a decrease in metastasis to the lungs and lymph nodes and no change in survival. LS2616 did not alter tumorigenicity of either sc or ic inoculations. In an in vivo neutralization assay, spleen cells of mice treated for 7 days with LS2616 demonstrated an increase in cytostatic or cytotoxic activity when incubated with B16F10 melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Metastasis of ocular and flank implants of the 13762NF mammary adenocarcinoma in syngeneic rats.

Solid fragments of a syngeneic tumor of low immunogenicity were implanted on the anterior surface of the iris or posterior surface of the cornea in young Fischer 344 rats. Growth and metastasis of these implants were examined and compared with those occurring following sc tumor implantation in the flank. Corneal implants did not grow well or metastasize. Iridial implants grew well, and tumor typically filled the eye within a few weeks. If tumor-filled eyes were left intact, all rats died or became moribund 7-9 weeks later. Metastasis was seen in the lungs (11/11), cervical lymph nodes (7/11), body wall (5/11), heart (4/11), kidney (4/11), and liver (3/11). Removal (enucleation) of tumor-filled eyes prior to spread to the orbit prevented the development of overt metastatic disease for 1-2 years (11/11). When healthy enucleated rats were necropsied 0 days to 26 weeks post enucleation, small nodules were seen in the lung (9/13), liver (3/13), or spleen (1/13). Nodules were not seen in rats that had been housed in our animal facility for 1-2 years (16/16), had eye surgery with tumor implanted on the posterior surface of the cornea (6/6), or had been subjected to the surgical procedures of corneal implantation and enucleation (3/3). When tumors were implanted sc, rats died after 6-7 weeks. Metastasis was seen in the lung (12/12), lymph nodes (12/12), spleen (1/12), and liver (1/12). Removal of very small flank tumors failed to prevent animals from dying 7-8 weeks later with pulmonary and lymph node metastasis (10/10). In summary, iridial implantation resulted in an altered pattern of metastasis. Animals that had iridial implants and enucleation failed to develop overt metastatic disease and had small nodules in the lung, liver, or spleen.

Adenocarcinoma↗

Ocular metastasis of in vivo and in vitro derived syngeneic murine melanoma.

We examine ocular metastasis of syngeneic murine melanoma in C57Bl/6J mice and compare the metastatic capability of B16F10 tumor cells maintained in vivo with those maintained in culture. We demonstrate that as long as the tumor cells are derived from an in vivo source, intraocular tumor readily metastasizes to the lungs. When in vivo derived tumor is introduced as an intracameral (ic) cell suspension, or as a solid fragment implanted on the iris, 100% of the animals die with extensive pulmonary metastasis 5-6 weeks later. In contrast, when B16F10 cells are passaged five times in culture and inoculated ic, a marked decrease in the frequency and extent of metastasis, and an increase in survival is seen. These studies demonstrate an alteration in the ability of cultured B16F10 cells to metastasize from the eye. When metastasis of in vivo derived tumor from the eye was compared with metastasis from an extraocular location, the extent and frequency of pulmonary metastasis and survival of hosts was the same. The effect of enucleation on the metastasis of B16F10 from the eye has only previously been examined using cultured cells. In this paper, we demonstrate that the efficacy of enucleation depends upon whether B16F10 melanoma cells have been passaged in vivo or in vitro.

Animals↗

A murine monoclonal antibody detecting N-acetyl- and N-glycolyl-GM2: characterization of cell surface reactivity.

Antisera reactive with the ganglioside GM2 were raised by immunizing C57BL/6 mice with the C57BL/6 melanoma JB-RH. Fusion with NS-1 was performed using splenic mononuclear cells from a mouse with high antibody titer. An immunoglobulin M monoclonal antibody (monoclonal antibody 5-3) was identified which was reactive with an antigen that was resistant to heat, trypsin, and Pronase. A panel of purified glycolipids was used to determine the specificity of monoclonal antibody 5-3. Reactivity was restricted to N-acetyl- and N-glycolyl-GM2. No reactivity was detected with asialo-GM2 or other gangliosides. Monoclonal antibody 5-3 was used to define the expression of GM2 on the cell surface of cultured human normal and malignant cells. Reactivity was seen with cell lines derived from 8 of 8 astrocytomas, 5 of 5 neuroblastomas, 7 of 9 sarcomas, 4 of 18 human melanomas, 2 of 4 murine melanomas, 4 of 37 epithelial cancers and with 0 of 6 skin fibroblast and 0 of 2 brain fibroblast lines. GM2, like GD2 and GD3, appears to be a differentiation antigen largely restricted to cells of neuroectodermal origin.

Animals↗

Investigation on serum C-peptide concentrations in pregnant diabetic women and in newborns of diabetic mothers.

Serum C-peptide concentrations at delivery and neonatal complications were investigated in a group of diabetic mothers and in their infants (IDM, n = 29). Furthermore, the changes in B-cell function and in daily insulin demand was followed up in 12 pregnant diabetics (of them 8 with long-term and 4 with short-term and "mild" diabetes) during pregnancy. All these diabetic mothers were under an intensive metabolic control with the aim to achieve normoglycaemia mainly in the second part of pregnancy. Mean cord blood C-peptide level of 29 IDM was 0,58 +/- 0,43 nmol/l, being not significantly higher than either the average C-peptide concentration of our adult control group (0,50 +/- 0,15 nmol/l, n = 24) or that of seven infants born to healthy mothers (0,58 +/- 0,37 nmol/l). Early hypoglycaemia was observed in five, macrosomia in three and IRDS in one neonate, resp. mothers coming to our intensive care after the 13th week of gestation gave birth with a higher incidence of neonatal complications than those controlled already in the first trimester or even preconceptionally. In 20 of 25 mothers studied venous C-peptide concentrations at delivery were undetectably low, in spite of their infants having cord blood C-peptide levels in the measurable range. In 8 of the 12 diabetic mothers with long-term diabetes C-peptide levels remained under the detection limit of the assay throughout pregnancy. In the 4 other cases with "mild" diabetes (and, hence, with a late start of intensive control) C-peptide values increased in the course of pregnancy; however, 3 of the four mothers gave birth with neonatal complications. These results indicate that (1) early--preferably preconceptional--intensive metabolic control of pregnant diabetics may reduce the incidence of neonatal complications; (2) fetal C-peptide can neither during pregnancy nor at birth pass through the placental barrier, and (3) mothers with "mild" diabetes require the same early and strict metabolic control as the more severe cases to avoid neonatal complications.

Adult↗