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P Nagy

Publications and source records attributed to P Nagy.

At least 73 records · Page 4Linked to original sources

[Reproducibility of malignancy grading in prostatic cancers using the Gleason-Böckling system].

Histologic slides from 50 cases of prostatic adenocarcinoma were evaluated by 5 pathologists, in order to test the reproducibility of grading in two systems. Twenty-five needle core biopsies and 25 surgical (adenomectomy) specimens were graded in two sessions, according to the histomorphologic criteria of Gleason and Böcking. The results were analyzed by the kappa statistics. In surgical specimens, there were no significant differences in the interobserver reproducibility of microscopically assessed categories. In needle biopsies, however, Gleason's primary pattern (62%, kappa = 0.42), and Böcking's histological pattern (63%, kappa = 0.37) showed the highest level of agreement. Among the computed (derivated) classification terms, those consisting of only 3 groups (Gleason grouping, kappa = 0.39; Böcking grade, kappa = 0.39) proved to be better reproducible than the corresponding score values (p < 0.05). When compressing both systems into two grades (high and "non-high"), reproducibility was improved (kappa = 0.52). For a substantial improvement of grading results, more accurate grade definitions, continuing training and regular consultation of pathologists are necessary. Based on the results obtained by intraobserver analysis we conclude that kappa statistics is of limited value when analyzing the role of individual experience at grading reproducibility.

Adenocarcinoma↗

[Relapsing polychondritis associated with myelodysplasia and acute eosinophilic leukemia].

Authors report a case in which relapsing polychondritis had been diagnosed two years before myelodysplastic syndrome developed and terminated in eosinophilic leukemia. The observation that relapsing polychondritis may precede myelodysplasia is not in concordance with some of the previous reports regarding relapsing polychondritis as a paraneoplastic phenomenon of myelodysplastic syndrome. The terminally developed eosinophilic leukemia is not supposed to be a blastic phase of the underlying myelodysplasia, much rather a second malignant process. This opinion may be confirmed by the early presence of blast cells in the myelodysplastic process without eosinophilia. It seems interesting to note that both our patient and his daughter suffered from diseases of autoimmune origin: acquired vitiligo and subacute cutan lupus erythematodes, respectively.

Aged↗

Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cells.

BACKGROUND/AIMS: Biliary epithelial cells (ductular oval cells) migrate into the periportal and midzonal parenchyma when hepatocyte regeneration after injury is significantly impeded. The potential of oval cells to differentiate into hepatocytes has been questioned. We have sought to resolve this issue using the modified Solt-Farber procedure in which 2-acetylaminofluorene is used to block hepatocyte regeneration in partially hepatectomized rats. METHODS: Rats received 2-acetylaminofluorene by oral gavage for 6 days before and up to 7 days after a two-thirds hepatectomy. The cellular reaction was visualized by the immunohistochemical localization of intermediate filaments cytokeratins 8 and 19 and vimentin, cytochrome P450 enzymatic proteins and alpha-foetoprotein. Expression of albumin and alpha-foetoprotein mRNA transcripts were observed in situ using antisense riboprobes. RESULTS: During the first 9 days after partial hepatectomy long strings of ductular cells spread outwards from the portal areas. These cells exhibited strong diffuse cytoplasmic staining with the anticytokeratin 8 and 19 antibodies, like authentic bile ducts, but in addition also expressed vimentin and alpha-foetoprotein (protein and mRNA)-collectively termed the "oval cell phenotype". Thereafter, these ducts rapidly vanished to be replaced by basophilic hepatocytes which lacked the oval cell phenotype, but which acquired strong expression of albumin mRNA. At 14 days after partial hepatectomy the oval cell phenotype was restricted to the peripheral margins of the newborn periportal hepatocytes, the distal tips of the oval cell ducts, and these too had disappeared within another 7 days. CONCLUSIONS: Ductular oval cells will differentiate into hepatocytes under appropriate experimental conditions.

Albumins↗

Fluorescent lipid probes 12-AS and TMA-DPH report on selective, purinergically induced fluidity changes in plasma membranes of lymphoid cells.

The effect of extracellular ATP (ATPex) on the anisotropy of 1-[4-(trimethylamino) phenyl]-6-phenyl-hexa-3,5 triene (TMA-DPH) and 12-anthroyloxi-stearic acid (12-AS) fluorescence was investigated in Balb/C mouse thymocytes and in JY human lymphoblasts. These cells have been shown recently to be sensitive and resistant to ATPex, respectively, in terms of cellular responses. Extracellular ATP (1 mM) induced a time-dependent elevation in the emission anisotropy of both probes (indicating an increased lipid packing density) in the plasma membrane of thymocytes. The maximal effect, at 37 degrees C, was observed between 20 and 60 min after ATPex administration, and followed by a gradual decrease of fluorescence anisotropy at longer times (60-180 min). ATPex did not change membrane fluidity of thymocytes below the phase transition temperature (at 18 degrees C). Oxidized ATP (oATP), a selective antagonist of P2z purinoreceptors, blocked the ATPex-induced decrease in membrane fluidity. Low ATPex concentrations (100-300 microM)--which are known to induce distinct signals (changes in membrane potential and intracellular Ph)--slightly fluidized the plasma membrane of thymocytes. This effect was partially blocked by quinine, a blocker of Ca(2+)-activated K+ channels. Neither 12-AS nor TMA-DPH showed any change in their emission anisotropy upon ATPex-treatment in the plasma membrane of the resistant human JY lymphoblast cells. No other signalling event (membrane potential change, Ca2+ response) is elicited by ATPex in this cell line. These data suggest that the changes in the membrane fluidity are likely consequences of specific, purinoreceptor-mediated signalling events, such as hyper-or depolarization of the plasma membrane or Ca2+ influx. These signals may induce changes in the conformation or lateral organization of membrane proteins, perturbing protein-lipid interactions, as well.

Adenosine Triphosphate↗

Zonal distribution of transcripts of four hepatic transcription factors in the mature rat liver.

Within the liver acinus the majority of genes are expressed in an ascending or descending gradient from the portal to the central vein. The regulatory factors involved in this spatial pattern of gene expression are still poorly understood. Many liver genes are regulated by liver-enriched transcription factors. Here we report on mRNA distribution of four transcription factors in cell lysates obtained from either the periportal or the perivenous region after zone-specific digitonin infusion and by in-situ hybridization. Northern blot analysis revealed that there were slightly more transcripts of C/EBP, HNF1 beta (n.s.) and HNF4 (p < 0.05), but fewer of HNF3 gamma (n.s.), in perivenous than in periportal lysates. A somewhat stronger staining in the perivenous region of HNF4 was also seen by in-situ hybridization. The moderate acinar zonation of the mRNAs of these transcription factors suggests that at best they could modulate but not govern the zonated expression of liver genes in the mature liver.

Animals↗

Are there any predictive factors for successful testicular sperm recovery in azoospermic patients?

Recovery of testicular spermatozoa from azoospermic patients with testicular failure followed by intracytoplasmic sperm injection (ICSI) is a recent advance in the treatment of male infertility. This study aimed at investigating which parameter(s) may predict successful testicular sperm recovery. We reviewed 395 testicular sperm recovery procedures and analysed the most frequently available parameters for clinical decision-making in azoospermic patients: (i) presence of at least one single spermatozoon in at least one preliminary semen analysis; (ii) maximum testicular volume; (iii) serum follicle stimulating hormone (FSH); and (iv) presence of spermatozoa in the histology of a randomly-taken testicular biopsy. Sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and accuracy were calculated for the above index parameters in different clinically relevant subgroups using receiver operating characteristic (ROC) curves whenever possible. Spermatozoa were always successfully recovered in patients with normal testicular histological findings (n = 173) or hypospermatogenesis (n = 16) but not in some patients with tubular sclerosis (seven out of 18), Sertoli cell-only pattern (55 out of 112) or maturation arrest (39 out of 76). Histopathology was the best test for predicting successful sperm recovery in the whole population (sensitivity: 86%, specificity: 93%, accuracy: 0.87). In patients with secretory azoospermia, histopathology was again the most accurate parameter (accuracy: 0.74), especially in patients showing Sertoli cell-only pattern (accuracy: 0.83) but not in patients showing maturation arrest (accuracy: 0.55). In patients with serum FSH concentrations > 12 IU/l and maximum testicular volume < 15 ml, histopathology was not found to be accurate. Semen analysis, maximum testicular volume and serum FSH were not highly predictive in all subgroups studied. Our analysis shows that no strong predictors for successful testicular sperm recovery are available except for testicular histopathology.

Adult↗

Computer simulated cost effectiveness of care management strategies on reduction of long-term sequelae in patients with non-insulin dependent diabetes mellitus.

Systems dynamics and computer "microworlds" offer a window on the long-term benefit of investing in aggressive care management for patients with non-insulin dependent diabetes mellitus. This article describes how clinicians, planners, payment specialists, and patients collaborated to make the business case for aggressive management of this disease.

Blood Glucose↗

Long term exposure to T-2 Fusarium mycotoxin fails to alter luteal function, follicular activity and embryo recovery in mares.

The effect of long term administration of T-2 toxin was studied in 6 Trotter mares during the summer and early autumn. After one complete oestrous cycle (Cycle 1) each mare was given 7 mg purified T-2 toxin per os daily (1 mg/ml in ethyl alcohol) beginning on Day 10 after ovulation in Cycle 2. Exposure to toxin was continued for 32-40 days, until Day 7 of Cycle 4. During this period all the animals remained in good physical condition, but skin lesions were observed around the mouth in 3 cases. Toxin administration had no effect on the length of the interovulatory interval or on the lengths of the luteal and follicular phases. It also had no effect on peripheral plasma progesterone profiles or follicular kinetics, including the growth rate and maximum size of ovulatory follicles and the maximum number, and time of first increase in number, of follicles larger than 1 and 2 cm. Uterine flushing was attempted in 5 mares and yielded 3 embryos (60%). These were of normal size and morphology and one was transferred nonsurgically to a recipient mare; a conceptus developed initially but it subsequently died and was resorbed. The results of the study allowed the conclusion that the administration of 7 mg/day T-2 toxin to mares in good body condition has no detrimental effect on ovarian activity, fertilisation or oviductal transport.

Animals↗

The current surgical treatment of primary malignant melanoma of the skin.

In our Department, between 1991 and 1996, 132 patients, there of 87 male-45 female, average age of 48.2 years underwent surgery because of stage 1 (T2) to stage 3 melanoma that was located on the skin. None of patients suffered from early or in situ melanoma. Our retrospective study was based on those 94 patients who had been followed up by Department or dermatology-oncology in our medical centre. Surgery is still the primary treatment for cutaneous malignant melanoma. Thin melanomas (up to 2 mm in thickness) can be excised with 2 cm margins. Whether this is also true for thicker melanomas is not known and the only way to obtain more knowledge is to participate in prospective randomised studies. Elective lymph node dissection is associated with significant morbidity which includes lymphedema, wound complications and paresthesias of the extremity. For this reason we use an alternative operative approach uses selective lymphadenectomy with identification of the sentinel node.

Dermatologic Surgical Procedures↗

Diagnostic-staging laparoscopy.

Recently instead of the old fashioned, traditional explorative laparotomy the newer up-to-date procedure, the diagnostic-staging laparoscopy has been generally used in the everyday surgical practice of the Authors. Evaluating 32 diagnostic and staging laparoscopy Authors draw the attention to the importance of this procedure which has high diagnostic value, and reduces the complication rate. Biopsy, cytology, frozen section can be done. Authors carries out diagnostic and staging laparoscopy in cases of esophageal, liver, stomach and pancreas tumours just immediately before surgery.

Abdomen↗

[Endoscope-assisted laparoscopic resection of the gastric wall].

The early gastric carcinomas measuring 10-25 mm in diameter, macroscopically I-II/C types and benign gastric tumours are relegated to laparoscopic wedge resection of the stomach. Authors report on the use of a new endoscopic assisted--"double-lifting"--laparoscopic resection of the gastric wall, in the course of removal of an early stage gastric carcinoma (13 mm in diameter, macroscopically II/C type) and a gastric lipoma (21 mm in diameter). The advantage of this method: the affected gastric wall could be removed safely far from the lesion and all layers of the gastric wall are available for histological examination.

Adult↗

Proteoglycan gene expression in rat liver after partial hepatectomy.

Liver regeneration is regulated by several factors. Among these extracellular matrix plays a crucial role in the restoration of normal structure. Proteoglycans are major components of extracellular matrix and they are able to bind growth factors implicated in liver growth. We studied syndecan, perlecan, fibroglycan, and decorin expression after partial hepatectomy in rats by Northern blot analysis. A strong early upregulation was observed at 30 min in decorin expression which was followed by the first syndecan and perlecan peaks at 2 and 4 hours after hepatectomy. At 24 hours, which is the peak of hepatocyte DNA synthesis, all these three proteoglycans had elevated steady state transcript level. Fibroglycan message decreased after partial hepatectomy and remained low during the experimental period. The different expression pattern of the proteoglycans suggests that these extracellular matrix components may selectively influence the regeneration process.

Animals↗

[Small intestinal leiomyoma causing gastrointestinal hemorrhage].

Leiomyomas are uncommon benign tumors of smooth muscle which may occur wherever smooth muscle is present. The small bowel is the most frequent site. Bleeding is the most common presenting symptom. Other symptoms, nausea, vomiting, abdominal pain are rare. In this article a 44 year-old male, presented, who was admitted with intermittent gastrointestinal bleeding in requence of jejunal leiomyoma with exulceration.

Adult↗

[Thrombosis in the small branches of the superior mesenteric artery in the early stages of essential thrombocythemia].

A tumour in the large bowel in a 67-year-old female patient was observed for the first time in 1991, and that is why a hemicolectomy was performed. Microscopic examination showed mucosal ulceration with chronic inflammation, but no malignancy was found. Small arteries in the bowel wall were occluded by organized and recanalized trombi. The pathologist thought it could be a rare visceral form of Buerger's disease. Two and a half years later essential thrombocythemia was diagnosed in the patient. On investigating her case-history the authors found that the myeloproliferative disease had already been in its early clinical stage in 1991. So the thrombotic events of the small arteries can be considered as the first sign of essential thrombocythemia. The authors concluded the observation of unusual and unexplained thrombotic events may suggest myeleproliferative disorders, even if their diagnostical criteria are not yet well manifested.

Aged↗

Proliferation, apoptosis, and induction of hepatic transcription factors are characteristics of the early response of biliary epithelial (oval) cells to chemical carcinogens.

In this study, we used [3H]thymidine labeling of newly synthesized DNA to examine the earliest effects of 2-acetylaminofluorene (2-AAF) on the mitotic activation of cells in the adult rat liver, and in situ hybridization analysis to study the expression of three transcription factors (HNF1 beta, HNF3 gamma, and HNF4), and two of the genes (alpha-fetoprotein [AFP] and albumin) regulated by these factors. A low dose of 2-AAF (and its analogs, 2-AF [2-aminofluorene] and N-OH-2-AAF) elicited a mitogenic response in ductal cells and nondescript periductular cells within 24 hours after administration. The compounds also induced the expression of HNF1 beta, HNF3 gamma, AFP, and albumin in ductal structures but had no detectable effect of HNF4 expression. In contrast, initiation of bile duct proliferation by ligation of the common bile duct had no effect on the expression of these genes in ductal cells. In addition to inducing a mitogenic response, 2-AAF resulted in increased numbers of apoptotic cells in the portal areas, a process that contributed to overall retention of liver morphology. Our results demonstrate that 2-AAF and some of its analogs can elicit a specific mitogenic response and induce expression of the "establishment" transcription factors, HNF1 beta and HNF3 gamma, in ductal cells. Our data provide further support of a precursor-product relationship between "stem-like" cells located in ductal structures, oval cells, and hepatocytes.

2-Acetylaminofluorene↗

In vivo infusion of growth factors enhances the mitogenic response of rat hepatic ductal (oval) cells after administration of 2-acetylaminofluorene.

Expression of several growth factors is elevated in rat liver, after induction of oval cell proliferation by chemical carcinogens. However, the exact roles played by individual factors are not defined. We infused and examined the effects of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) on the proliferation of ductal and periductal cells after their activation with 2-acetylaminofluorene (2-AAF). Furthermore, we included studies on urokinase-type plasminogen activator (uPA), because Northern blot analysis showed a strong coincidence of uPA expression with oval cell proliferation. Low doses of 2-AAF were used to activate ductal and periductal cells, whereafter growth factors were infused. Infusion of EGF, HGF, uPA, or any combination thereof for up to 7 days resulted in increased numbers of [3H]thymidine-labeled ductal and periductal cells expanding into the liver acinus. Although the growth factors all increased the number of labeled cells, they preferentially acted on different cell populations. Although exposure to 2-AAF alone or combined with infusion of HGF resulted in proliferation of almost equal numbers of ductal and Ito cells, infusion of EGF and any combination hereof resulted in 75% to 80% of labeled cells having a ductal phenotype. Also, infusion of EGF and HGF resulted in decreased numbers of cells undergoing apoptosis in response to 2-AAF. Our results demonstrate that, although 2-AAF acts as a mitogenic stimulus for ductal and periductal cells, growth factors are necessary for survival, motility, and expansion of these cells into the liver acini.

2-Acetylaminofluorene↗