Search PubMed⌕ Search

Biomedical subjects

P Nagy

Publications and source records attributed to P Nagy.

At least 91 records · Page 5Linked to original sources
PubMed1996

The antiandrogen cyproterone acetate induces synthesis of transforming growth factor beta 1 in the parenchymal cells of the liver accompanied by an enhanced sensitivity to undergo apoptosis and necrosis without inflammation.

Recently, cases of liver damage and liver tumors have been reported after treatment of prostate cancer patients with the antiandrogen cyproterone acetate (CPA). In rat liver, CPA initiates a wave of DNA synthesis that is accompanied by apoptosis. In apoptotic hepatocytes, a latent form of transforming growth factor beta 1 (TGF-beta 1) is detectable by immunohistochemistry. Injection of a single dose of TGF-beta 1 induces apoptosis in the liver of animals pretreated with CPA but has an insignificant effect in untreated animals. In this study, we show by Northern analysis that there is increased expression of TGF-beta 1 in the liver after CPA treatment. Detection of TGF-beta 1 with in situ hybridization showed that TGF-beta 1 was synthesized in the parenchymal cells. Time course and dose-response experiments performed 48 hours after the last application of CPA showed that apoptotic nuclei with chromatin condensed at the nuclear periphery (AN) were already visible 2 hours after injection (0.13%), and apoptotic bodies (ABs) increased 2 to 9 hours after the injection (from 1.28% to 6.67%) after 25 micrograms TGF-beta 1/kg. At 4.5 hours after injection, an induction of apoptosis could be detected with 0.25 microgram TGF-beta 1/kg and after the maximum dose (250 micrograms TGF-beta 1/kg) ANs (0.24%) and ABs (16.74%) were homogeneously distributed throughout the liver lobe. Irrespective of the dose or time after injection of TGF-beta 1, 82% of the ABs were localized within hepatocytes. Liver enzymes were detected in high amounts in the serum (eightfold elevation of glutamate dehydrogenase, fivefold elevation of alanine transaminase [ALT]) 7 hours after the first visible sign of apoptosis. After an additional 20 hours, the liver contained many necrotic figures. These results suggest that the combination of TGF-beta 1 expression coupled with a strikingly enhanced sensitivity to the induction of apoptosis could be responsible both for the liver damage and the development of liver tumors observed after treatment with CPA.

Androgen Antagonists↗
PubMed1996

Outcome of intracytoplasmic sperm injection with testicular spermatozoa in obstructive and non-obstructive azoospermia.

From 1 August 1993 until 30 September 1994, 69 couples suffering from azoospermia underwent testicular sperm extraction and intracytoplasmic sperm injection. In 50 couples with obstructive azoospermia a total of 631 metaphase-II oocytes were injected after testicular sperm extraction yielding a 2-PN fertilization rate of 57%. In female patients <40 years of age an ongoing pregnancy rate per transfer of 42% (14/33) was obtained. So far, eight healthy babies have been born, including two singletons and three twin gestations. In 19 couples with non-obstructive azoospermia a total of 264 metaphase-II oocytes were injected after testicular sperm extraction, yielding a 2-PN fertilization rate of 58%. An ongoing pregnancy rate per transfer of 31% (5/16) was established. So far, six healthy babies have been born including one singleton, one twin and one triplet gestation.

Adult↗
PubMed1996

A new method to measure portal venous and hepatic arterial blood flow in patients intraoperatively.

The intraoperative measurement of the afferent circulation of the liver, namely the hepatic artery flow and portal venous flow was carried out upon 14 anesthetized patients having carcinoma in the splanchnic area, mainly in the head of the pancreas by means of transit time ultrasonic volume flowmeter. The hepatic artery flow, portal venous flow and total hepatic flow were 0.377 +/- 0.10; 0.614 +/- 0.21; 0.992 +/- 0.276 l/min respectively. The ratio of hepatic arterial flow to portal venous flow was 0.66 +/- 0.259. There was a sharp, significant increase in hepatic arterial flow (29.8 +/- 6.1%, p < 0.01) after the temporary occlusion of the portal vein, while the temporary occlusion of hepatic artery did not have any significant effect on portal venous circulation. The interaction between hepatic arterial flow and portal venous flow is a much disputed question, but according to the presented data here, it is unquestionable, that the decrease of portal venous flow immediately results a significant increase in hepatic artery circulation.

Abdomen↗
PubMed1996

Changes in hepatic hemodynamics due to primary liver tumours.

Data regarding the afferent circulation of the liver in patients with primary hepatocellular carcinoma are controversial, we have carried out measurement of hepatic arterial and portal venous flow intraoperatively by transit time ultrasonic volume flowmetry. In patients with primary hepatocellular carcinoma the hepatic artery flow increased to 0.55 +/- 0.211 compared with the control value of 0.37 +/- 0.102 1/min. (p < 0.01). The portal venous flow decreased from 0.61 +/- 0.212 l/min. to 0.47 +/- l/min. P < 0.01). Due to the opposite changes in the afferent circulation the total hepatic blood flow did not change significantly, compared with controls. The ratio of hepatic arterial flow to portal vein flow increased to 1.239 +/- 0.246 in patients with hepatocellular carcinoma, which is double of the control value (0.66 +/- 0.259 l/min). After resection this ratio did not change. The resection did not alter hepatic artery or portal venous flow significantly, although the total hepatic blood flow decreased significantly (p < 0.01). On the basis of our early results it is possible that the ratio of the two circulations may be to deel measured with doppler ultrasound and provide diagnostic information.

Adult↗
PubMed1996

Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive renal disease.

Several lines of evidence suggest that local production of transforming growth factor-beta (TGF-beta) contributes to renal disease, particularly to the accumulation of the extracellular matrix protein that characterizes glomerulosclerosis and interstitial fibrosis. We have examined whether elevated levels of circulating TGF-beta adversely affect the kidney. We have studied mice that are transgenic for an active form of TGF-beta 1 under the control of murine albumin promoter and enhancer DNA sequences. These mice express the transgene exclusively in the liver and have elevated plasma concentrations of TGF-beta 1. Renal disease was seen in two of three lines of Alb/TGF-beta 1 transgenic mice; these two lines had the highest levels of hepatic transgene expression and the highest plasma TGF-beta 1 levels. Histologic abnormalities, which included mesangial expansion and thickened capillary loops, were noted in the glomeruli by 3 weeks of age. Interstitial fibrosis and tubular atrophy appeared subsequently. Mice from Line 25, the line with highest levels of TGF-beta 1, developed proteinuria by 5 weeks of age. These mice subsequently manifested nephrotic syndrome with ascites and progressive azotemia; uremic death occurred in more than 25% of the mice by 15 weeks of age. The glomeruli contained immune deposits in subendothelial and mesangial locations, but complement deposition was infrequent. Ultrastructural examination revealed an increase in extracellular matrix material, including collagen fibrils, in subendothelial and mesangial locations. Increased levels of circulating TGF-beta 1 induced progressive renal disease that was characterized by mesangial expansion, accumulation of glomerular immune deposits and matrix proteins, and interstitial fibrosis in this transgenic mouse model. These data suggest that chronically elevated circulating levels of TGF-beta 1 induce progressive glomerulosclerosis.

Animals↗
PubMed1996

Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha.

We have previously shown that co-expression of c-myc and transforming growth factor (TGF)-alpha as transgenes in mouse liver results in major enhancement of neoplastic development in this organ as compared with expression of either of these transgenes alone. In this report we describe in detail the progression from liver cell dysplasia to hepatocellular carcinomas (HCCs) occurring in the liver of c-myc/TGF-alpha and c-myc transgenic mice. Despite morphological similarities in the sequence of events between the two transgenic lines, the dramatic acceleration, extent, and severity of hepatic lesions in c-myc/TGF-alpha mice clearly demonstrated the synergistic effects of this transgenic combination. Although c-myc/TGF-alpha and c-myc females displayed longer latency and lower tumor incidence, the pathological changes were the same as those seen in the male mice, including the formation of HCCs, which are absent in TGF-alpha single-transgenic females. Tumors in single- and double-transgenic mice showed induction of the endogenous c-myc and TGF-alpha and, most frequently, unchanged or decreased epidermal growth factor receptor, further indicating the collaborative role of c-myc and TGF-alpha in providing a selective growth advantage to tumor cells independently of the epidermal growth factor receptor levels. To identify possible tumor precursors, we focused particularly on the dysplastic changes preceding and accompanying the appearance of preneoplastic and neoplastic lesions in the double-transgenic mice. Early on, these changes were characterized by the appearance of large dysplastic hepatocytes, mostly pericentrally, expressing high levels of TGF-alpha and uPA, as well as TGF-beta 1, particularly in apoptotic cells. After a short period of replication and expansion into the liver parenchyma, as well as penetration into the central veins, these cells underwent apoptotic cell death while preneoplastic and neoplastic lesions were forming. The peritumorous tissues also contained small dysplastic hepatocytes and oval-like cells, similar to those found in the tumors. Transplantation of the transgenic liver tissues harboring only dysplasia with or without vascular lesions onto nude mice was able to yield HCCs composed of small diploid cells, suggesting that initiated cells are generated during the early dysplastic phase and can progress to HCC. It is therefore likely that large dysplastic hepatocytes undergo apoptosis, which may be closely associated with the up-regulation of TGF-beta 1 and uPA, whereas other cells evolve into the precursor population for HCC. Due to the simultaneous presence of c-myc, TGF-alpha, and dysplasia in premalignant human liver diseases, our transgenic mouse system appears to be an appropriate model for studying human hepatocarcinogenesis.

Animals↗
PubMed1996

Influence of a deficient intake of high and low degradable protein on body composition, metabolic adaptation, production and reproductive performance in early lactation dairy cows.

High-yielding dairy cows (n = 34) were divided into high (HD) and low (LD) protein degradability groups after delivery, and used for a feeding trial which lasted up to day 80 +/- 10 of lactation. The cows were regularly weighed, their body condition was scored (BCS), and their reproductive status assessed. Blood samples were taken simultaneously, and ruminal fluid was collected on the last day of the trial. On postpartum day 45 +/- 6 and 11 days thereafter two prostaglandin F2 alpha (PGF2 alpha) injections were administered. The ammonia and urea concentrations of the ruminal fluid were higher in cows of group HD. The C2:C3 ratio was 2.7:1 vs. 2.3:1 in HD and LD cows, respectively. The amino acid and lipid composition of blood reflected the dietary treatments. The BCS and blood urea concentration were slightly higher in HD animals. The average daily milk production of LD cows was 1.5 kg higher than that of HD cows. The pregnancy rates of the two groups at day 200 after calving did not differ, but LD cows showed their first visible oestrus and reconceived significantly (p < 0.05) later. It can be concluded that--at a marginal energy supply-a moderate (13%) deficiency of rumen-degradable protein during the first 10 weeks after calving can be more detrimental to reproductive performance than a severe (27%) deficiency of undegradable protein.

Adaptation, Physiological↗
PubMed1995

[Neurofibromatosis (von Recklinghausen disease) and carcinoid tumor in Vater's ampulla].

The localization of the carcinoid tumors of the gastrointestinal tract--as a part of the APUD system--is extremely seldom at the region of ampulla of Vater. A case of congenital neurofibromatosis is reported in a 49-year-old male patient, with a carcinoid tumor of the ampulla of Vater in the background of long-standing, atypical biliary complaints. Periampullary neoplasm of neural-crest origin are very rare, up to this time 73 cases of Vater papilla carcinoid tumors were described. Regarding the development of VP carcinoid in neurofibromatosis, our patient is the 21st reported case in the world literature, and the first one in Hungary. The authors review the literature, giving special attention to the risk of periampullary neoplasms in von Recklinghausen's disease, the need of accurate diagnosis and the correctly selected operative intervention.

Ampulla of Vater↗
PubMed1995

Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions.

Aberrant expression of transforming growth factor beta 1 (TGF-beta 1) has been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions. To determine the in vivo effects of overexpression of TGF-beta 1 on the function and structure of hepatic as well as extrahepatic tissues, transgenic mice were generated containing a fusion gene (Alb/TGF-beta 1) consisting of modified porcine TGF-beta 1 cDNA under the control of the regulatory elements of the mouse albumin gene. Five transgenic lines were developed, all of which expressed the Alb/TGF-beta 1 transgene selectively in hepatocytes. The transgenic line 25 expressing the highest level of the transgene in the liver also had high (> 10-fold over control) plasma levels of TGF-beta 1. Hepatic fibrosis and apoptotic death of hepatocytes developed in all the transgenic lines but was more pronounced in line 25. The fibrotic process was characterized by deposition of collagen around individual hepatocytes and within the space of Disse in a radiating linear pattern. Several extrahepatic lesions developed in line 25, including glomerulonephritis and renal failure, arteritis and myocarditis, as well as atrophic changes in pancreas and testis. The results from this transgenic model strongly support the proposed etiological role for TGF-beta 1 in a variety of fibrotic and inflammatory disorders. The transgenic model may also provide an appropriate paradigm for testing therapeutic interventions aimed at neutralizing the detrimental effects of this important cytokine.

Animals↗
PubMed1995

Amniocentesis before 15 weeks' gestation: technical aspects and obstetric risks.

In a prospective case-control study, early amniocenteses (EAC, n = 242) at between 12 and 14 weeks gestation, were compared with standard amniocenteses (SAC, n = 242) performed at between 15 and 24 weeks gestation. The medical records of these 484 cases were reviewed for indications, success rate, color and volume of amniotic fluid, gestational age, number of needle insertions, location of the placenta, culture failure rate, obstetric complications and therapeutic abortion rate. There were no significant differences between the two groups in success rate, in culture success rate or in the outcome of the pregnancies. The volume of the sample taken was smaller in the EAC patients (P < 0.001), and therapeutic abortions were performed significantly earlier (P < 0.02.) Results show that EAC is feasible from 11 weeks' gestation, and can be performed for the usual indications as an alternative to chorionic villus sampling. In the near future, cytogenetic techniques will enable results to be obtained in less than a week.

Adult↗
PubMed1995

Ion-channel activities regulate transmembrane signaling in thymocyte apoptosis and T-cell activation.

Several examples have shown that plasma membrane ion channels (e.g., Ca2+ and K+ channels) make an important contribution to lymphocyte activation or thymocyte apoptosis. Here we report on the importance of these ion channels in the sensitivity or resistance of lymphoid cells to extracellular ATP-induced apoptosis. Thymocytes of Balb/c mice responded to extracellular ATP (ATPex) sensitively, with an immediate increase in the intracellular calcium level and later with an increased membrane permeability to low MW markers. Mature (medullary) thymocytes showed a higher sensitivity than did cortical thymocytes. Three human lymphoma cell lines, including SUPT13, a cell line reported to be sensitive to TcR/CD3 activation-induced apoptosis, showed a high resistance to ATPex action. These observations suggest that maturation/differentiation state-dependent activity or disappearance of early ATP-receptor operated signaling systems (including ion channels) are critical for the cells in developing towards apoptosis. Using the patch-clamp technique we demonstrated that bretylium tosylate (a particular K(+)-channel blocker) known as inhibitor of T-lymphocyte proliferation also influences the single-channel properties of voltage-gated K+ channels through depressing whole-cell K+ currents. This finding is yet another example underlying the importance of K+ channel activity in T-lymphocyte proliferation.

Adenosine Triphosphate↗
PubMed1995

Oval cell differentiation into hepatocytes in the acetylaminofluorene-treated regenerating rat liver.

When hepatocyte regeneration after a two-thirds partial hepatectomy (PH) in rats is blocked by oral gavage of acetylaminofluorene, a proliferation of ductular cells ensues that results in a profusion of neoductules radiating from each portal tract. To examine the possibility that this population of newly emerging cells harbors cells capable of differentiating into hepatocytes, we have looked in these cells for expression of functional markers of hepatocyte commitment at both the RNA and protein levels. Expression of albumin and alpha-fetoprotein (alpha-FP) messenger RNA (mRNA) transcripts were sought in situ using antisense riboprobes, and the expression of a number of cytochrome P450 enzymes was examined immunohistochemically. Before any signs of differentiation the ductular cells strongly expressed cytokeratins 7, 8, 18, and 19 in the same manner as authentic bile ducts, but unlike the latter also expressed vimentin. In situ hybridization studies showed that small bile ducts close to the limiting plate, as well as the newly formed ducts, expressed albumin and alpha-fetoprotein messenger RNAs, and immunocytochemistry showed that the distribution of the respective proteins was similar. Beginning at 1 week after partial hepatectomy, areas of differentiation could be found in the new ducts, with cells resembling either columnar intestinal-type epithelia or hepatocytes. Intestinal-like cells expressed neither albumin, alpha-FP, nor cytochrome P450 enzymes, whereas ductular cells appearing like hepatocytes with the typical membranous distribution of cytokeratin 8 strongly expressed a variety of cytochrome P450 enzymes normally associated with functional hepatocytes. These observations further support the belief that reactive ductules, sprouted from small ducts, can represent an adaptive response of the liver to replenish lost hepatocytes, although some of the newborn cells appear to differentiate along intestinal lines.

2-Acetylaminofluorene↗
PubMed1995

Effect of uterus position relative to the pelvic inlet on the accuracy of early bovine pregnancy diagnosis by means of ultrasonography.

A 5-MHz sector transducer (experiment 1) and a 7.5 MHz linear-array transducer (experiment 2) were used for early pregnancy diagnosis in two Hungarian dairy herds under field conditions. In the first experiment, ultrasound scanning was conducted three times at 3 or 4-day intervals between 24 and 33 days after artificial insemination (AI), while in the second experiment, it was performed two times at 7-day intervals between 27 and 38 days post-insemination. Significantly more incorrect non-pregnancy diagnoses were made between 24 and 33 days (first experiment) and between 27 and 38 days (second experiment) after AI in cows in which the uterus was located far cranial to the pelvic inlet than in animals in which the uterus was located within or close to the pelvic inlet at the first ultrasonographic examination.

Animals↗
PubMed1995

Recent concepts in the management of infertility because of non-obstructive azoospermia.

Testicular biopsy has been widely used for the diagnosis of male infertility. Since the introduction of intracytoplasmic sperm injection (ICSI), spermatozoa recovered from a testicular biopsy specimen can be successfully used for establishing pregnancies. A few spermatozoa may be recovered from a wet preparation of a testicular biopsy, not only in obstructive azoospermic patients, but also in many patients with non-obstructive azoospermia. In 36 out of 38 non-obstructive azoospermic patients sperm cells were recovered from a testicular biopsy specimen. However in two patients, spermatozoa could not be found after further preparation of the biopsy specimens for ICSI. In the remaining 32 patients, a normal fertilization rate of 56.8% per successfully injected oocyte was obtained after ICSI of testicular spermatozoa. In 84% of patients, embryos were replaced with an overall pregnancy rate of 28.9% per testicular biopsy or 34.3% per embryo transfer. The results clearly indicate that at present an excisional testicular biopsy should be offered to all azoospermic patient, irrespective of concentration of follicle stimulating hormone, testicular size or medical history.

Biopsy↗
PubMed1995

The interaction between hepatic arterial and portal venous blood flows; simultaneous measurement by transit time ultrasonic volume flowmetry.

Intra-operative measurement of the afferent circulation of the liver, namely hepatic artery and portal venous flow was carried out in 14 anesthetized patients with carcinoma of the splanchnic area, mainly in the head of the pancreas, by means of transit time ultrasonic volume flowmetry. The hepatic artery flow, portal venous flow and total hepatic flow were 0.377 +/- 0.10; 0.614 +/- 0.21; 0.992 +/- 0.2761/min, respectively. The ratio of hepatic arterial flow to portal venous flow was 0.66 +/- 0.259. There was a sharp, significant increase in hepatic arterial flow (29.8 +/- 6.1%, p < 0.01) after the temporary occlusion of portal vein, while the temporary occlusion of the hepatic artery did not have any significant effect on portal venous circulation. The interaction between hepatic arterial flow and portal venous flow is much in dispute, but, as the data presented here show, there is no doubt that the decrease in portal venous flow immediately gives rise to a significant increase in hepatic artery circulation.

Blood Flow Velocity↗