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Biomedical subjects

A Kiss

Publications and source records attributed to A Kiss.

At least 109 records · Page 6Linked to original sources

Neurotoxic lesions induced by monosodium glutamate result in increased adenopituitary proopiomelanocortin gene expression and decreased corticosterone clearance in rats.

Hypothalamic-pituitary-adrenocortical function in rats with brain lesions induced by neonatal monosodium glutamate (MSG) treatment (4 mg/g, 5 administrations, i.p.) was evaluated in the present study. Using in situ hybridization we found increased proopiomelanocortin (POMC) mRNA levels in the adenopituitary and normal corticotropin-releasing hormone mRNA levels in the hypothalamic paraventricular nucleus in MSG-treated rats. The total content of pituitary adrenocorticotropin (ACTH) was not changed, while pituitary ACTH concentration was higher in MSG-treated compared to control rats. The number of ACTH-immunostained cells per a constant area of adenohypophysial section, as measured by immunohistochemistry, was unchanged indicating that no significant condensation of corticotropes occurred. Basal plasma ACTH concentrations were not different, whereas morning corticosterone levels were elevated in rats with MSG treatment. While ACTH response to stress stimuli was similar in both groups of rats, corticosterone response to exogenous ACTH (500 ng/kg, i.v., Synacthen), short-lasting handling and immobilization was of the same magnitude but prolonged in MSG-treated rats. Based on the decline of [3H] corticosterone in plasma, a decreased corticosterone clearance rate was found in MSG-treated rats. These findings suggest that MSG treatment results in increased POMC gene expression per corticotrope of the atrophic pituitary resulting in maintenance of normal pituitary ACTH stores and plasma ACTH levels. Elevated basal levels of corticosterone in plasma as well as prolonged corticosterone responses to stimulations in rats treated with MSG seem to be due to a decreased clearance rate of corticosterone.

Adrenal Cortex↗

Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma.

Oxidative stress contributes to airway inflammation and exhaled hydrogen peroxide (H2O2) and nitric oxide (NO) are elevated in asthmatic patients. We determined the concentrations of expired H2O2 and NO in 116 asthmatic (72 stable steroid-naive, 30 stable steroid-treated, and 14 severe steroid-treated unstable patients) and in 35 healthy subjects, and studied the relation between exhaled H2O2, NO, FEV1, airway responsiveness, and eosinophils in induced sputum. Both exhaled H2O2 and NO levels were elevated in steroid-naive asthmatic patients compared with normal subjects (0.72 +/- 0.06 versus 0.27 +/- 0.04 microM and 29 +/- 1.9 versus 6.5 +/- 0. 32 ppb, respectively; p < 0.001) and were reduced in stable steroid-treated patients (0.43 +/- 0.08 microM, p < 0.05, and 9.9 +/- 0.97 ppb, p < 0.001). In unstable steroid-treated asthmatics, however, H2O2 levels were increased, but exhaled NO levels were low (0.78 +/- 0.16 microM and 6.7 +/- 1.0 ppb, respectively). There was a correlation between expired H2O2, sputum eosinophils and airway hyperresponsiveness (methacholine PC20). Exhaled NO also correlated with sputum eosinophils, but not with airway hyperresponsiveness. Our findings indicate that measurement of expired H2O2 and NO in asthmatic patients provides complementary data for monitoring of disease activity.

Administration, Inhalation↗

Changes in oncogene expression implicated in evolution of chronic granulocytic leukemia from its chronic phase to acceleration.

Expression of nine oncogenes was investigated in cell samples from fifteen patients with Philadelphia chromosome (Ph)-positive chronic granulocytic leukemia (CGL) both at diagnosis and at the onset of accelerated phase (AP) of the disease. The bcr-abl fusion gene, the H-ras gene and the c-myb gene were universally expressed. In comparison with the chronic phase (CP) of the disease, an increase in the levels of bcr-abl-, c-myb- and H-ras-related transcripts was found in three, two and three AP samples, respectively. Elevation of the bcr-abl-related message was associated with duplication of the Ph chromosome and amplification of the bcr-abl fusion gene in one AP sample. No CP samples were positive for c-myc or c-sis expression. On the contrary, c-myc and c-sis were expressed in three and four AP samples, respectively. The presence of c-myc-related transcript was associated with trisomy 8 with or without amplification of the c-myc oncogene in leukemia cells of two patients with CGL in AP. No changes of oncogene expression were found in four AP samples. However, we observed deletions of chromosome 13 and 17 or i(17q) in three of them, suggesting that tumor suppressor gene alterations may also be responsible for the development of AP of CGL. Our data indicate that heterogeneous alterations in oncogenes and tumor suppressor genes accompany the evolution of CGL-CP to the AP of the disease.

Acute-Phase Reaction↗

Distribution profile and in vivo RNA association of cytoplasmic AU-rich sequence binding proteins in various mammalian cells: effect of the organizational state of cellular architecture.

With the aid of sequential detergent fractionation and label transfer techniques, in this study we monitored the distribution of cytoplasmic AU-rich sequence binding proteins (AUBP) in different cell types. We show here that cells of various origin display diverse AUBP profiles when the presence and abundance of AUBPs were compared in two major cytoplasmic compartments, the non-ionic detergent-soluble and -insoluble fractions. We also demonstrate that different RNA probes derived from AU-rich 3'-UTR elements of various cytokine and proto-oncogene mRNAs detect distinct AUBPs within the same cell. When the in vivo association of these proteins with AU-rich RNA was assessed using the combination of in vivo UV-crosslinking and label transfer methods, we found that detachment of monolayer cells by trypsinization or disruption of the microfilament network by Cytochalasin treatment prior to UV light exposure, led to selective changes in both the cytoplasmic distribution and in vivo RNA association of many AUBPs. These data indicate that the organizational state of cytoarchitecture may influence processes involved in AUBP-mediated mRNA metabolism.

Actin Cytoskeleton↗

Laparoscopic varicocele operation: a chance to prevent the recurrence.

There are recurrences and postoperative hydrocele of varicocele after any kind of surgical treatment. Laparoscopic clipping and dissection of internal spermatic vessels was performed without any complication in 73 children to treat varicocele in our department between 1995 and 1998. We have used a new method to detect etiological factors at laparoscopic surgery. The well-known Linton and Trendelenburg test was adapted to detect incidental collateral veins in 73 patients. Using these test, collateral veins were detected in 16 boys. The testicular artery identified in most of the cases as a pulsatile vessel. The operating time was 10-25 minutes. Laparoscopic varicocelectomy is a safe, effective treatment causing minimal discomfort and allowing patients an early to return to activity. These results suggest this technique a viable alternative to open ligation in paediatric urological practice.

Adolescent↗

[Pure red cell aplasia, associated with chronic lymphoid leukemia, successfully treated with closorine].

Pure red cell aplasia (PRCA) is a rare disorder, which is characterized by severe anaemia associated with reticulocytopenia and absence of erythroid precursor cell from the bone marrow. Mostly immunological mechanisms have a role in its pathogenesis. Primarily the acquired, idiopathic type occurs in adults, however, it is rarely associated with other disorders (autoimmune-, and lymphoproliferative diseases, etc.). The authors present a patient with B-cell chronic lymphocytic leukemia associated with PRCA, which was successfully treated with cyclosporine. The pathogenesis and the therapy of the PRCA is also summarized.

Cyclosporine↗

Retinoic acid inhibition of cell cycle progression in MCF-7 human breast cancer cells.

Cell cycle analysis indicates that retinoic acid (RA) inhibition of MCF-7 cell growth occurs through induction of G1 arrest with a concomitant reduction in the proportion of cells in S and G2 + M phases. RA did not affect cyclins D1, A, and E and cyclin-dependent kinase 2 (CDK2) expression, but significantly reduced cyclin D3 and CDK4 expression after 24 h. RA also inhibited cyclin B1 and CDC2 expression, possibly responsible for the reduction of the proportion of cells in G2 + M and S phases. RA did not induce p16 and p27 expression, but obviously reduced p21 level in MCF-7 cells. The retinoid markedly reduced pRB protein level and abrogated pRB phosphorylation after 48 h; it also reduced transcription factor E2F1 expression at both the mRNA and protein levels. E2F1 promoter activity was reduced by 60%, which is probably responsible, at least in part, for the reduction of E2F1 expression in RA-treated MCF-7 cells. These observations demonstrate a marked effect of RA on some of the key cell cycle regulatory proteins in MCF-7 cells. Cyclin D3 and CDK4 are likely the early targets of RA, followed by reduced pRB expression and phosphorylation, as well as by the inhibition of the E2F1 transcription factor which controls progression from G1 to S phase. Most of these events precede the observed reduction in MCF-7 cell growth, which begins at Day 3 of RA treatment.

Breast Neoplasms↗

Growth inhibition and induction of apoptosis by HGF in transformed rat liver epithelial cells.

Recently we demonstrated in a transgenic mouse model that hepatocyte growth factor (HGF) inhibits c-myc dependent hepatocarcinogenesis. The inhibitory effects of HGF in carcinogenesis were further characterized using a series of rat liver epithelial (RLE) cell lines which were transformed in vitro with either aflatoxin or oncogenes, or spontaneously. HGF caused a cytostatic effect and enhanced cell motility in spontaneously and aflatoxin-transformed cells. In normal RLE cells HGF was slightly stimulatory and did not induce scattering. The HGF receptor was tyrosine phosphorylated in all cell lines, indicating that it is functionally active and capable of signaling events. In the aflatoxin transformed cells HGF also induced apoptosis, associated with constitutive c-myc expression and 1 Kb bax-alpha transcripts. These findings indicate that transformed RLE cell lines may provide a useful model to further examine the mechanism(s) by which HGF and its receptor modulate neoplastic development.

Animals↗

Footprint analysis of the bsp RI DNA methyltransferase-DNA interaction.

The interaction between the GGCC-specific Bsp RI DNA methyltransferase (M. Bsp RI) and substrate DNA was studied with footprinting techniques using a DNA fragment that was unmodified on both strands. Footprinting with DNase I revealed an approximately 14 bp protected region. Footprinting with dimethylsulfate detected major groove interactions with the guanine bases of the recognition sequence. Reaction with 1,10-phenanthroline-copper did not show protection, suggesting that minor groove interactions play little role in sequence-specific recognition by M. Bsp RI. Hydroxyl radical footprinting revealed a protected stretch of 6 nt. The hydroxyl radical footprint of M. Bsp RI differs markedly from the the footprint reported for the Hha I and Sss I methyltransferases. The pattern of protection from dimethylsulfate and hydroxyl radicals suggests that the interactions of M. Bsp RI with DNA are similar to those detected in the co-crystal structure of the Hae III methyltransferase.

Copper↗

Regulation of pituitary corticotropin releasing hormone (CRH) receptor mRNA and CRH binding during adrenalectomy: role of glucocorticoids and hypothalamic factors.

The role of glucocorticoids and hypothalamic factors on CRH receptor expression in the pituitary were studied by analysis of the effects of adrenalectomy and suppression of CRH and VP secretion by hypothalamic lesions in the rat. Consistent with previous in situ hybridization studies, Northern blots showed that pituitary CRH receptor mRNA decreased only transiently after adrenalectomy, falling to 51% of the control levels after 18 h, and returning to control values after 6 days (112%). The early decrease was prevented by dexamethasone injection, 100 micrograms, s.c. The role of increased levels of CRH and VP in the pituitary portal circulation on the transient decrease in CRH receptor mRNA levels after adrenalectomy were studied by in situ hybridization in rats subjected in PVN lesions or median eminence deafferentation by hypothalamic anterolateral cuts (ALC). PVN lesion (12 days) or ALC (8 days) resulted in undetectable irCRH and VP in the external zone of the median eminence and had no effect on basal levels of pituitary POMC mRNA, CRH binding and CRH receptor mRNA. In sham lesioned rats, adrenalectomy for 18 h or 4 days caused the expected increases in pituitary POMC hnRNA and mRNA, and decreases in CRH binding. CRH-R mRNA levels decreased by about 50% after 18 h adrenalectomy but returned to basal by 4 days. PVN lesion or ALC fully prevented the fall in CRH binding after 18 h or 4 days adrenalectomy and the increase in POMC mRNA after 4 days adrenalectomy, whereas only attenuated the decrease in CRH receptor mRNA and increase in POMC mRNA levels after 18 h adrenalectomy. Administration of a CRH antagonist did not affect CRH receptor mRNA and POMC hnRNA and mRNA indicating that residual CRH in the median eminence after hypothalamic surgery is not responsible for the effect of adrenalectomy. These studies confirm previous in situ hybridization studies showing that adrenalectomy causes transient decreases in pituitary CRH receptor mRNA levels. The data indicate that while increases in hypothalamic CRH secretion following glucocorticoid withdrawal mediate pituitary CRH receptor binding loss and the increase in POMC expression after long-term adrenalectomy, CRH only partially accounts for the early changes in CRH receptor mRNA and POMC mRNA.

Adrenal Glands↗

Outcome in emotionally related living kidney donor transplantation.

BACKGROUND: The growing shortage of cadaver kidneys, the limited possibilities to expand the living related donor pool and the good results obtained in our centre with poorly matched cadaver kidneys, led us in 1991 to begin accepting highly motivated, unrelated, living kidney donors who had a strong emotional bond with the recipients. METHODS: Between 1 January 1991 and 1 January 1996, 46 potential living kidney donors and their emotionally related recipients were evaluated. Twenty-three cases were accepted for renal transplantation after thorough somatic and psychological evaluation. The mean post-transplant follow-up until 1 April 1996 was of 28 +/- 3 months. Compatible blood groups and a negative cross-match were mandatory, but no minimal HLA matching was required. RESULTS: There was a 50% drop-out rate following the initial screening. The main reasons for not performing transplantation were immunological contraindications in 39% of the cases, somatic in 30.5%, psychological in 26% and socioeconomic in 4.5%. In the accepted group of recipients, 48% (11/23) received transplants without chronic dialysis. Donor survival was 91%; two deaths unrelated to nephrectomy occurred 1 year after donation. The 2-year actuarial recipient and graft survivals were 100% and 91% respectively, compared to 99% (recipients) and 93% (grafts) in the non-HLA-identical living related kidney transplant group, and to 93% (recipients) and 83% (grafts) in the cadaver kidney transplant group. Recipient rehabilitation was completed after 4 +/- 1 months. Emotionally related donors returned to work 5 +/- 2 weeks after nephrectomy, and no donor regretted his decision, even in the case of failure. CONCLUSIONS: Kidney transplantation from emotionally related living donors represents a valuable option, allowing more patients with end-stage renal disease to avoid chronic dialysis. Recipient and graft outcomes were superior to cadaver kidney transplantation. Motivated and emotionally related donors should be allowed to donate one of their kidneys provided that they are carefully selected and thoroughly informed.

Emotions↗

Regulation of pituitary V1b vasopressin receptor messenger ribonucleic acid by adrenalectomy and glucocorticoid administration.

Regulation of the number of pituitary vasopressin (VP) receptors plays an important role in controlling pituitary responsiveness during alterations of the hypothalamic pituitary adrenal axis. The mechanisms regulating these VP receptors were studied by analysis of the effects of adrenalectomy and glucocorticoid administration on V1b receptor (V1b-R) messenger RNA (mRNA) by Northern blot and by in situ hybridization in the rat. Adrenalectomy transiently decreased V1b-R mRNA levels by 18 h (77% and 62% for the 3.7-kb and 3.2-kb bands in the Northern blots, and 50% by in situ hybridization), returning to basal levels after 6 days. The decrease in V1b-R mRNA after 18 h adrenalectomy was fully prevented by dexamethasone (100 microg s.c.) but not by elimination of hypothalamic CRH and VP by paraventricular nucleus lesions or median eminence deafferentation. In sham-operated rats, dexamethasone increased receptor mRNA by 50% after 6 days. In contrast to Sprague-Dawley rats, in Brattleboro rats (di/di), which lack hypothalamic VP, adrenalectomy caused a sustained decrease in V1b-R mRNA levels (<50% of controls by 6 days). The data show that pituitary V1b-R mRNA is positively regulated by glucocorticoids and that the recovery of V1b-R mRNA levels after prolonged adrenalectomy is probably mediated by VP. In addition, the data suggest that the down-regulation of VP binding after long-term adrenalectomy is due to posttranscriptional events rather than to changes in V1b-R mRNA.

Adrenalectomy↗

Differential regulation of hypothalamic pituitary corticotropin releasing hormone receptors during development of adjuvant-induced arthritis in the rat.

The expression of corticotropin releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) and CRH receptor mRNA in the PVN and anterior pituitary was studied during development of adjuvant-induced arthritis in Piebald-Viral-Glaxo rats, using in situ hybridization techniques. As previously shown with i.p. hypertonic saline injection, basal and immobilization stress-stimulated CRH mRNA levels in the PVN were significantly lower than in controls 14 days after adjuvant injection. However, 7 days after injection, preceding the onset of inflammation, the increase of CRH mRNA following immobilization was significantly higher than in control rats. In contrast to other chronic stress paradigms, inflammation stress failed to induce type-1 CRH receptor (CRH-R1) mRNA in the PVN, either at 7 days, or at 14 days after adjuvant injection, when inflammation is present. The ability of acute immobilization to induce CRH-R1 mRNA in the PVN was not affected 14 days after adjuvant injection but parallel to the CRH peptide mRNA response it was markedly potentiated at 7 days. Pro-opiomelanocorpin (POMC) mRNA levels in the anterior pituitary increased significantly 14 days after adjuvant injection, and they were unaffected by 1 h immobilization. While CRH binding in the pituitary decreased significantly 14 days after adjuvant injection, CRH-R1 mRNA was unchanged. This study shows biphasic hypothalamic responses to acute stress during development of adjuvant-induced arthritis, with enhanced CRH peptide and CRH-R1 mRNAs responses at 7 days, preceding the onset of inflammation, and blunted CRH mRNA responses at 14 days at the height of the inflammatory response. The lack of CRH receptor expression in the PVN in this model of chronic inflammation stress associated to low hypothalamic CRH peptide levels supports the view that positive feedback regulation by CRH is necessary to maintain enhanced CRH expression during chronic stress.

Animals↗

Downregulation of major histocompatibility complex class I expression and susceptibility to natural killer cells in cells transformed with the oncogenic adenovirus 12 are regulated by different E1A domains.

All adenoviruses transform rodent cells in vitro, but only cells transformed by serotypes belonging to subgroups A (Ad12) and B (Ad3) are tumorigenic for immunocompetent animals. In these cells, the expression of major histocompatibility complex (MHC) class I antigens is repressed and might allow them to escape from recognition by cytotoxic T lymphocytes and to develop in tumor. Furthermore, these cell lines appear resistant to lysis by natural killer (NK) cells. To determine the E1A domain(s) responsible for these properties several cell lines were created by transforming baby rat kidney cells with a set of plasmids expressing different Ad2/Ad12 hybrid E1A gene products. The class I gene expression was inhibited in cells expressing the Ad12 13S mRNA product and in cells transformed with Ad2/Ad12 hybrid E1A gene product harboring the C-terminal part of the conserved region (CR) 3 of Ad12. Susceptibility of these transformed cell lines to NK cells was determined by cytolytic assays. The results obtained suggest that two of Ad12 E1A domains are required to induce resistance of the cell lines to NK cells.

Adenoviridae↗

Interdisciplinary treatment of the malignant lymphoma of the thyroid.

720 patients with malignant tumor of the thyroid were treated at our department between 1950 and 1996. Histological examination revealed 15 cases (2%) of malignant lymphoma (14 female, 1 male mean age: 69.8 year). In 8 cases Hashimoto thyroiditis, in 1 case chronic lymphocytic thyroiditis was verified beyond the lymphoma. According to Ann Arbor staging, 9 patients were stage I E, 3 II E, 1 III E, and 2 IV E. Radical surgical treatment was performed in 7, palliative in also 7, and only biopsy in one case. Irradiation was administered in 9, chemotherapy in 8 patients. In 5 out of the 7 palliative operated patients tracheostomy was performed. 10 patients were lost. The therapy of the non-Hodgkin lymphoma of the thyroid is debated in the literature. There are some authors, who question the role of surgery. Our experience, based on the longer survival of the patients, who underwent radical operation, support those, who consider the possible surgical treatment as the initial part of the multimodal therapy.

Aged↗

[Gallbladder torsion. A case report].

INTRODUCTION: The unusual anatomical position of the organ, generally suspended by a mesentery, allows the rare possibility of its torsion with necrosis and even perforation. CASE REPORT: A woman, aged 78, who presented signs and symptoms similar to those of severe acute cholecystitis: abrupt onset of pain and a large palpable mass below the right costal margin. Immediate laparotomy with detorsion and easy cholecystectomy was performed. CONCLUSIONS: Should a greatly enlarged mass be palpable below the right costal margin within a few hours from the abrupt onset of unremittant abdominal pain the possibility of torsion should come to mind not to delay operation in the supposition of acute cholecystitis.

Abdominal Pain↗