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Biomedical subjects

J Nagy

Publications and source records attributed to J Nagy.

At least 91 records · Page 5Linked to original sources

[Relationship between intestinal permeability and antibodies against food antigens in IgA nephropathy].

Elevated antibody titers to food antigens and increased intestinal permeability in IgA nephropathy (IgA NP) suggest that these factors may be interdependent and play a role in the pathogenesis of the disease. In 1989 IgA and IgG antibodies against eight common food antigens were examined in the sera of 35 IgA NP patients and 12 controls using the ELISA method. Intestinal permeability was determined in 29 IgA NP patients and 20 controls using the 51Cr-EDTA test. Both examinations were carried out in 17 patients. Twenty-one patients allowed the intestinal permeability examinations to be repeated five years later. Compared with controls, significantly elevated IgA antibody titers against gliadin, soy, HAV (salt extracted antigens of oat flour) and ovalbumin were found. Intestinal permeability was significantly higher in IgA NP patients both in 1989 (3.86% +/- 0.29 vs. control, 2.72% +/- 0.23; p < 0.005) and in 1994 (4.57% +/- 0.63; p < 0.02) than in controls. A strong correlation was observed between the intestinal permeability and the IgA type of antibody titers against soy (p < 0.01; r = 0.72) and HAV (p < 0.02; r = 0.57). In patients without azotemia (serum creatinine > 150 mumol/l; n = 22) the decrease in creatinine clearance was significant only in the cases of increased intestinal permeability. On the basis of these data we assume that there is a connection between intestinal permeability and the production of IgA type antibody against food antigens in least a proportion of patients with IgA NP, and as a results of the lasting increase in intestinal permeability the production and the mesangial deposition of IgA immunocomplexes also increase.

Antibodies↗

Hepatocyte growth factor/scatter factor expression and c-met in primary breast cancer.

Hepatocyte growth factor/scatter factor (HGF/SF) is a fibroblast-derived cytokine whose receptor is encoded by c-met. Activation of c-met promotes tumour cell proliferation, dissociation, invasiveness and angiogenesis. Aberrant expression of HGF/SF or c-met may play a role in tumour progression. HGF/SF and c-met were determined in 73 breast cancers (median follow up: 61 months) and 10 samples of tumour-free breast tissue. HGF/SF was detected at significantly higher concentrations in breast cancers (median 350, range 58-1604 ng per 100 mg total protein) when compared with normal breast tissue (median 108, range 66-213 ng per 100 mg total protein) (P < 0.001). C-met was detected in all 10 samples of tumour-free breast tissue and in 26 breast cancers. HGF/SF concentrations correlated with disease relapse (P < 0.001) and reduced overall survival (P < 0.001). Tumours with detectable c-met correlated significantly with disease-relapse (P = 0.012). Multivariate analysis demonstrated a significant interaction between HGF/SF and c-met in relation to disease-relapse (P = 0.014). These results suggest a biological interaction involving HGF/SF and c-met in promoting tumour progression in breast cancer.

Breast↗

Compression of the pituitary stalk elicits chronic increases in CSF vasopressin, oxytocin as well as in social investigation and aggressiveness.

The neurochemical and behavioural effects of a novel stereotaxic surgical method developed for interrupting the nerve fibres running through the rat pituitary stalk to the posterior pituitary gland was studied. The cerebrospinal fluid (CSF) vasopressin (AVP) and oxytocin (OT) content as well as changes in aggressiveness were measured in rats one week and one month after the surgical intervention. The main results are as follows: (1) the compression of the pituitary stalk elicits a chronic increase in water consumption, as well as in CSF vasopressin and oxytocin content; (2) the surgical intervention increased the frequency of clinch fighting after one week. The increase in aggressiveness accentuated after one month and, in addition, operated animals showed reduced scores of resting while exploratory and social behaviours increased; (3) there was a strong positive correlation between water consumption, vasopressin, and aggressiveness; (4) oxytocin changes showed a positive correlation with variation in social behaviour. The surgical intervention may serve as a model for lesions of the pituitary stalk and formation of ectopic neurohypophyses in humans.

Aggression↗

Do intestinal hyperpermeability and the related food antigens play a role in the progression of IgA nephropathy? I. Study of intestinal permeability.

Intestinal permeability was investigated by using 51Cr-EDTA as a probe molecule in 29 patients with immunoglobulin A nephropathy (IgA NP) and 20 healthy controls in 1990. Intestinal permeability was significantly higher in the IgA NP patients than in the controls (IgA NP, 3.86 +/- 0.29%; controls, 2.72 +/- 0.23%, p < 0.005). There was a significant relation between the manifestations of the disease (proteinuria and/or microhematuria) and the increased intestinal permeability (p < 0.05). By 1994, after an interval of 4 years, average intestinal permeability in the 21 patients available for study had not changed (3.80 +/- 0.36 vs. 4.57 +/- 0.63%) and was significantly higher than in the controls (p < 0.02). In patients with elevated serum IgA levels (serum IgA > 3.2 g/l; n = 15) there was a significant correlation between serum IgA levels and the degree of intestinal permeability (p < 0.02). During the 4-year period, the patients' kidney function deteriorated (n = 25; creatinine clearance in 1990, 92.4 +/- 6.1 ml/min; in 1994, 73.9 +/- 7.6 ml/min; p < 0.0002), the deterioration being greater in patients with increased intestinal permeability. There was no relation between the histologic grade of the biopsy specimen, hypertension and intestinal permeability. These data collected over a 4-year period suggest that in IgA NP increased intestinal permeability may play a role in the pathogenesis of the disease and adversely influence its progression.

Adult↗

[The effect of the duration of administration of epidural analgesia on delivery].

UNLABELLED: The authors compared the length of labour periods, number of surgical deliveries, the use of oxytocin, analgetics, spasmolytics and intensity of pain in two groups of primiparae, who were in labor under continuous epidural analgesia (CEA). In the first group CEA was started when the cervix was dilated not more than 3 cm, in the second one when the cervix was dilated more than 3 cm. The length of labour, oxytocin consumption and frequency of vaginal surgery did not differ in the two groups. In the first group there was great consumption of analgetics and spasmolytics, more motor blocks of the lower extremities and a higher rate of Caesarean sections on account of dystocia. In some of the women of the first group the intensity of pain at the end of the first stage of labour and during the second stage was higher than before the onset of CEA. CONCLUSION: It seems to be better to start CEA when the cervix is dilated more than 3 cm.

Analgesia, Epidural↗

Paracetamol induced acute interstitial nephritis superimposed on mesangiocapillary glomerulonephritis.

We report the case of a young alcoholic male whose first renal biopsy disclosed mesangiocapillary glomerulonephritis. One month later he took 1.5 g paracetamol to control the fever. Soon he got hospitalized due to toxicoderma, elevated liver and renal function tests. While the liver enzymes returned to normal, uremia developed. A repeated renal biopsy revealed severe interstitial inflammation, tubular atrophy. Haemodialysis was started and he got steroids (1 mg/kg body weight). He showed considerable recovery of renal function in some weeks. The case points to the possibility that paracetamol-even in therapeutic dosage-might result in hepatic and renal damage in alcoholics.

Acetaminophen↗

[Chronic IgM mesangioproliferative glomerulonephritis].

In their ten years renal biopsy material authors found nine cases of chronic glomerulonephritides with predominantly IgM deposition in the mesangium which reach the diagnosis of IgM nephropathy. This paper on the basis of a typical case deal with the immunopathology, diagnosis, prognosis and therapy of the disease.

Adult↗

New short-chain analogs of a substance-P antagonist inhibit proliferation of human small-cell lung-cancer cells in vitro and in vivo.

Human small-cell lung-cancer cells (SCLC) produce and secrete gastrin-releasing peptide (GRP), the mammalian equivalent of bombesin (BN). There is some evidence to suggest that GRP is an autocrine regulator of SCLC cell growth. In the search for potent BN antagonists, several substance-P (SP) analogs were found to inhibit the growth of SCLC cells. We found that a known short-chain SP antagonist, pHOPA-DTrp-Phe-DTrp-Leu-Leu-NH2(NY3238), inhibits the binding of 125I-Tyr4-BN on Swiss 3T3 cell line expressing BN receptors, as well as the proliferation of NCI-H69 SCLC cells. In this study we tested several analogs of NY3238 and we found that NY3521 and NY3460 are more effective in inhibition of proliferation of SCLC cells but less potent in inhibition of binding of 125I-Tyr4-BN on Swiss 3T3 cells than NY3238. Furthermore, we detected specific binding of radiolabelled NY3238 even below 1 nM on NCI-H69 cells that could have been inhibited by SP and NY3460 rather than by BN. In addition to these in vitro studies, NY3460 proved to be effective in inhibiting the growth of NCI-H69 SCLC xenografts in nude mice in vivo. These analogs of NY3238 could be promising therapeutic agents in the treatment of SCLC.

3T3 Cells↗

Expression and loss of heterozygosity of c-met proto-oncogene in primary breast cancer.

The c-met proto-oncogene encodes the receptor to hepatocyte growth factor-scatter factor (HGF-SF), a mesenchyme-derived cytokine with cell-dissociating, invasion, and angiogenic properties. The expression of c-met in breast cancer is the subject of controversy; 111 primary breast cancers were examined for LOH of c-met by Southern blot electrophoresis. c-met expression was measured in a further 40 patients with breast cancer and in 8 patients with benign breast disease by flow cytometry. LOH of c-met was detected in only 4% of informative breast cancers. Expression of c-met was significantly greater in patients with breast cancer than in those with benign breast disease (P < 0.01, Mann-Whitney). There was no correlation however between increased c-met expression and clinicopathological prognostic variables. These results do not support the role of c-met as a tumour suppressor gene in breast cancer but suggest increased receptor expression in malignant breast disease. The significance of this increased expression in breast cancer is the subject of further investigation.

Blotting, Southern↗

Ingestive response shows absence of taste aversion after bovine satietin in rats.

Six adult male rats (409 +/- 16 g) were equipped with chronically implanted oral catheters. Facial consummatory responses to gustatory stimuli, of 50 microliters 2.0 mol.1-1 banana or coconut flavoring, were recorded on a +4/-4 scale for 30 s. The new flavors were paired with IP injections on three different days. The rats were injected with either saline or 1 mg.kg-1 bovine serum satietin (bs-SAT). Food intake and body weight were reduced (p < 0.005) after satietin but not after saline. Both coconut and banana flavors aroused mild ingestive responses in the naive rats. Five days after the beginning of the pairing with IP injections, the rats' response to coconut and banana remained unchanged. The results show that satietin was able to reduce food intake and body weight but did not arouse taste aversion.

Animals↗

Determination of octanol-water partition coefficients by an HPLC method for anticonvulsant structure-activity studies.

Octanol-water partition coefficients have been measured and calculated for eight clinically relevant anticonvulsants. For some compounds, these are the first experimentally available log P values. For the remainder of the molecules, new values have been suggested. The utility of the micro shake-flask experimental method and the ALOGP calculational method in determining anticonvulsant log P values has been demonstrated.

1-Octanol↗

Altered humoral immunity against cytomegalovirus and Epstein-Barr virus without detectable virus antigens and virus-DNA in the glomeruli of patients with IGA nephropathy in remission phase.

Herpes viruses, such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV), very often occur in the nasopharynx. A pathogenetic role of these viruses in immunoglobulin A nephropathy (IgA NP) is a challenging hypothesis, since upper respiratory tract infections are frequently and closely related in time to the acute episodes of IgA NP. However, conflicting reports have been published in this field. We compared the IgA and IgG antibody (AB) titres against cytomegalovirus (CMV) in sera of 41 IgANP patients with 80 healthy controls. The prevalence rates of CMV-IgA and CMV-IgG AB were significantly higher in patients with IgA NP than in healthy controls (CMV-IgA, titre > = 8, p < 0.001; CMV-IgG, titre > = 16, p < 0.05). There was also a significant difference in the concentration of CMV-IgA AB between IgANP patients and controls (IgA NP: 0.34 +/- 0.66, healthy controls: 0.06 +/- 0.33, mean +/- SD, p = < 0.002), but not in the concentration of CMV-IgG AB between NP patients and controls. While examining 60 patients with IgA NP and 75 healthy controls a significantly elevated prevalence rate of IgA AB against EBV capsid antigen (EBV-VCA) was also detected in the sera of IgA NP patients vs controls (titre > = 16; p < 0.05). There was no significant difference in the prevalence of IgG AB to EBV-VCA between patients with IgA NP and healthy controls, except at titre = 1024 (p < 0.05). At a follow-up, CMV-IgA persisted in 4 of 5, and EBV-VCA-IgA in 8 of 12 seropositive patients with IgA NP. We could not detect virus antigens or virus deoxyribonucleic acid (DNA) in the glomeruli of NP patients either with immunohistology using a monoclonal antibody or with the DNA in situ hybridization technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vitro degradation of thymopoietin32-35 in human, dog and rat plasma.

TP4 (Arg-Lys-Asp-Val) is a synthetic immunomodulatory tetrapeptide of Chemical Works of Gedeon Richter Ltd. The aim of this study was to give comparative data on the in vitro degradation of 14C-TP4 in plasma of different species at two TP4 concentrations to allow suitable extrapolation of preclinical data to human system. The results show that the degradation was very fast in each plasma and varied by the species and concentrations studied. In rat, dog and human plasma for initial concentration of 80 micrograms/ml and 800 micrograms/ml the apparent half-life values proved to be 1.4, 1.8, 2.7 and 3.9, 6.3, 13.6 minutes, respectively. The most susceptible breakdown point was the peptide bond between Arg and Lys. The correlation between TP4 degradation and arginine formation was demonstrated by a straight line with a correlation coefficient of 0.99565 and a slope close to -1.

Adjuvants, Immunologic↗

Possible pathogenic role of IgE in Henoch-Schönlein purpura.

The incidences of clinical and biological markers of atopy were investigated in 16 children with IgA nephropathy (IgAN) (group A) and in 22 with Henoch-Schönlein purpura nephritis (HSPN) (group B). The incidence of increased plasma IgE levels according to age-matched normal values was significantly higher in group B (17/22, 77%) than in group A (7/16, 44%) (P < 0.05). Although not significant, the incidences of positive RAST tests and of a history of typical atopic symptoms were also higher in group B [10/22 (45%) and 11/22 (50%), respectively] than in group A [4/16 (25%) and 5/16 (31%), respectively]. Moreover, IgE deposits were demonstrated by a peroxidase/anti-peroxidase method on cutaneous Langerhans and mast cells in 4 of 6 patients with HSPN. Thus immunoallergy might account, in some cases, for the cutaneous, intestinal and pulmonary signs observed in HSPN, but not in IgAN. We postulate stimulation of IgE-sensitized mast cells by specific antigens in the presence of IgA circulating immune complexes (CIC), release of vasoactive substances, increased capillary permeability and perivascular deposition of IgA CIC.

Adolescent↗