Expression of transforming growth factor-beta 1 in human non-Hodgkin's lymphoma xenografts.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to P Nagy.
Explore the source record for details and available documents.
In the therapeutically important range (100-200 micrograms/ml), suramin was found to increase the phagocytic activity of human monocytes (measured by the uptake of Saccharomyces cerevisiae and sensitized sheep red blood cells) in vitro. Suramin itself was a chemotactic signal for monocytes and increased the chemiluminescence of neutrophil granulocytes. Suramin seems to act via the ATP-binding P2 receptors of human phagocytes.
Transforming growth factor-beta 1 was localized by means of immunohistochemical reaction in liver biopsy specimens taken from patients having different chronic liver diseases with extending fibrosis. Two polyclonal antibodies that were produced in rabbits were directed against the amino terminal of transforming growth factor-beta 1. Staining by anti-CC(1-30) was primarily extracellular and located in the portal and periportal fibrotic areas of all seven cases with chronic active hepatitis. No staining was noted in the four chronic persistent cases studied. A strong reaction was seen with the antibody in nine of the ten cirrhotic samples, whereas it was negative in one inactive cirrhosis case and in all five cases with normal liver histological findings. No positive staining could be detected by the anti-LC(1-30) in any of the liver tissues. Detection of transforming growth factor-beta 1 in active liver diseases at the site of fibrosis suggests that transforming growth factor-beta 1 might have a role in the process and progression of fibrosis during the development of the disease.
Explore the source record for details and available documents.
In Szabolcs-Szatmár county between January 1 1983 and December 31, 1987, 465 new cases of adult malignant haematologic diseases were registered by authors. The authors present the yearly distribution of cases, and analyse the main types and characteristics of the disease entity. According to their data the epidemiology of leukaemia/lymphoma in their county is equivalent to that of European and North American, therefore that may be considered as a standard for their whole country. Their work is date-collecting, it is still going on. Authors want to have more exact informations about epidemiology of leukaemia/lymphoma in their county. Their results have great importance in organizing and continuous assuring of modern treatment of haematologic malignancies. Their data would probably allow to make etiopathogenetic and therapeutic conclusions in a few years.
The cellular distribution and temporal expression of transcripts from transforming growth factor-beta 1 (TGF-beta 1) and procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) genes were studied in carbon tetrachloride (CCl4)-induced rat liver fibrosis by using in situ hybridization technique. During the fibrotic process, TGF-beta 1 and procollagen genes were similarly and predominantly expressed in Desmin-positive perisinusoidal cells (e.g., fat-storing cells and myofibroblasts) and fibroblasts and their expression continued to be higher than those observed in control rats. These transcripts were also observed in inflammatory cells mainly granulocytes and macrophage-like cells at the early stages of liver fibrosis. The production of extracellular matrix along small blood vessels and fibrous septa coincided with the expression of these genes. Expression of TGF-beta 1 and procollagen genes were not detected in hepatocytes throughout the experiment. No significant differences in cellular distribution or time course of gene expression among procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) were observed. Desmin-positive perisinusoidal cells and fibroblasts appeared to play the principal role in synthesis of collagens in CCl4-induced hepatic fibrosis. The simultaneous expression of TGF-beta 1 and procollagen genes in mesenchymal cells, including Desmin-positive perisinusoidal cells, during hepatic fibrosis suggests the possibility that TGF-beta 1 may have an important role in the production of fibrosis.
Forty-one histologically verified endometrial carcinomas were examined to reveal relationship, if any, between cytoplasmic receptor content and tumour differentiation, cytologic diagnosis and mean nuclear surface area. The latter in itself was found to be a reliable prognostic sign of the estrogen receptor positivity of the tumour.
The physical association of HLA class I and class II Ag in the membranes of PGF and JY lymphoblastoid cell lines was studied using flow cytometric energy transfer. This technique measures the proximity of cell surface molecules in the nm range and provides a distribution histogram of the average proximity of molecules on each cell of a population. HLA Ag were labeled with mAb conjugated to fluorescein, serving as donor, or tetramethylrhodamine, serving as acceptor molecules. Significant fluorescence energy transfer was detected between various combinations of class I and class II molecules indicating that these molecules are within 10 nanometers of each other. Specifically, energy transfer was observed between class I molecules and DR, DQ, or DP class II HLA molecules. In addition, energy transfer between all combinations of DR, DQ, and DP molecules was observed. No transfer was observed among class I molecules or among DR or among DP molecules. Among DQ molecules, subpopulations transferred fluorescence energy to each other. The close contact measured between class I and class II Ag correlates with previous reports of cocapping and may reflect an immunologically significant interaction or the reported tendency of class I Ag to associate with other cell surface receptors, including growth factor receptors. The energy transfer between fluorescent antibodies to class II Ag suggests the existence of heterodimers formed from the different locus products, as well as possible quaternary surface interactions between alpha/beta complexes from separate loci.
On the basis of random selection 1 g of Rocephin was given to 36 parturients following Cesarean section to prevent postoperative febrile diseases. The results confirm the role of antibiotic prophylaxis in the prevention of perioperative infections. If only partial prophylaxis may be applied preference has to be given to the so called risk cases.
The Solt-Farber protocol, in the absence of an initiating agent, was used to examine the precursor-product relationship between oval cells and hepatocytes in rat liver. The animals were administered 2-acetylaminofluorene (AAF) by gavage for 2 wk combined with partial hepatectomy 1 wk after administering AAF Two dose levels of AAF were used: 9- and 21-mg total dose for animals in Groups I and II, respectively. [3H]Thymidine was administered i.p. to one-half of the animals at Day 6 post-partial hepatectomy. Animals were sacrificed 7, 9, 11, and 13 days after surgery. Only oval cells became labeled on Day 7 in both groups. On Day 9 both labeled oval cells and labeled basophilic hepatocytes were present in Group I, whereas in Group II only oval cells remained labeled. On Days 11 and 13 both oval cells and basophilic hepatocytes were labeled in both groups. The total amount of radioactivity in Group II livers remained the same on Day 9 when only labeled oval cells were present and on Days 11 and 13 when both labeled oval cells and labeled basophilic hepatocytes were present. The calculated half-life for basophilic hepatocytes was about 50 h. The differentiation of oval cells into basophilic hepatocytes was delayed in Group II as compared to Group I, and the higher dose of AAF also induced the formation of both intestinal metaplasia and bile duct formation. In situ hybridization with an alpha-fetoprotein probe showed a strong expression in groups of typical oval cells and in cells arranged in duct-like structures. In addition a transient expression of AFP was also observed in the areas of basophilic hepatocytes 9 to 11 days after partial hepatectomy. Administration of AAF decreased the level of albumin mRNA in preexisting hepatocytes and caused a significant decrease of serum albumin. In contrast, oval cells showed a strong albumin expression, and basophilic hepatocytes formed islands of albumin-expressing cells. Oval cells and the foci of early basophilic hepatocytes lacked glucose-6-phosphatase activity. At Day 13 significant numbers of basophilic hepatocytes were positive for glucose-6-phosphatase. Oval cells were strongly gamma-glutamyltranspeptidase positive, whereas the foci of basophilic hepatocytes were negative for gamma-glutamyltranspeptidase. Only occasionally were transiently gamma-glutamyltranspeptidase-positive hepatocytes observed in basophilic foci. In summary our data indicate that oval cells can differentiate to hepatocytes and may have an important physiological function as a source of major serum proteins when hepatocytes are unable to synthesize these proteins.
Transforming growth factor-beta 1 (TGF-beta 1) is capable of eliciting a myriad of biological responses associated with cellular proliferation, as well as effects unrelated to the control of cell growth. We examined the possible role of TGF-beta 1 in the differentiation of rat liver epithelial (RLE) cells in vitro and studied the cellular distribution of TGF-beta 1 transcripts and protein during in vivo differentiation of oval cells. Furthermore, we followed the cellular distribution of TGF-beta 1 transcripts and protein during chemical hepatocarcinogenesis. By using in situ hybridization and immunohistochemical techniques, we showed that both TGF-beta 1 transcripts and protein are localized in nonparenchymal cells in normal liver, are expressed in oval cells during very early stages of hepatocytic differentiation in vivo, and are exclusively expressed in the nontumorous mesenchymal cell compartment during hepatocarcinogenesis. Furthermore, we showed that TGF-beta 1 is capable of inducing differentiation of RLE cells in vitro consistent with early stages of hepatocytic lineage differentiation. Our data indicate that the RLE cells similar to the oval cells in vivo may be an epithelial progenitor cell for hepatocytic cell lineage in adult mammalian liver.
Axon terminals which could be interpreted as dorsal root boutons, were photographed from a series of 98 ultrathin sections with a Jeol 100B electron microscope. A total of 13 boutons were recovered for computer reconstruction. Two of them were terminal boutons, eight en passant boutons and three boutons were only partially recovered. All boutons contained multiple synaptic sites (maximum 33 and minimum seven) at which axodendritic and axoaxonic synapses were established. Axodendritic synapses were of the asymmetric type and they were directed toward adjacent dendrites. In axoaxonic synapses, which were of the symmetric type, the boutons were invariably on the postsynaptic side. Among the presynaptic profiles axons with spherical and pleomorphic vesicles and dendrites with flattened vesicles could be discerned. On average, each 2.67-microns2 bouton surface area contained one presynaptic site at which an axodendritic synapse was established, and each 7-microns2 surface area contained one postsynaptic site for an axoaxonic (or dendroaxonic) contact. A tendency of grouping of synaptic sites was observed. Distance measurements between the closest neighbours of all synaptic sites were made in four combinations in boutons with the original and with a random distribution of synaptic sites. The arithmetic mean of distances measured between the presynaptic and the closest postsynaptic sites was almost twice as big as that measured in the reverse direction. The difference between these values became greatly reduced in the case of random distribution. The arithmetic mean of distances between the closest neighbours of presynaptic sites was about the same as that between the closest neighbours of postsynaptic sites. This latter value was considerably increased with randomly distributed synaptic sites. The results suggest a non-random distribution of synaptic sites on the surface of boutons. The analysis of cluster formation of synaptic sites performed with a numerical taxonomy technique revealed that the majority of the 153 synaptic sites were comprised in 27 clusters containing both pre- and postsynaptic sites within the 1-micron similarity level. All postsynaptic sites were within 1 micron of one or more presynaptic sites. On the basis of the assumption that the postsynaptic sites are occupied by inhibitory axoaxonic synapses, it is suggested that the transmitter release from the presynaptic sites can be individually controlled in this structural arrangement. A probable mechanism of this function may be the passive invasion of the bouton by the impulse propagating actively along the dorsal root fibre.
Authors compared the results of 242 cytologic examinations of patients suffering from endometrial carcinoma with the histologic picture of the tumour. Conventional methods of cytodiagnostic screening in case of less differentiated tumours were found to give better results. Results of hormonal cytologic examinations demonstrate that there is an inverse relation between differentiation of tumour and maturity of vaginal epithelium. The authors analyze this observation with regard to the receptor theory of the malignant transformation of the endometrium.
Favourable experiences of the wire-osteosynthesis performed in 237 cases in the Oral-Surgical Department of the Budapest Semmelweis Kórház between 1 January 1985 and 30 June 1988 are reported on. Such method has recently been fallen into the background. Therefore, attention is called to the necessity and advantages of the wire-osteosyntheses.
The expression of cellular myc (c-myc) was studied during early and late stages of chemical hepatocarcinogenesis in the rat using Northern blot analysis and in situ hybridization. Hepatocarcinogenesis was induced according to the resistant hepatocyte model of Solt and Farber. An uninitiated version of this model was also used to examine the expression of c-myc during proliferation and differentiation of oval cells. The expression of c-myc was increased throughout hepatocarcinogenesis starting with early preneoplastic foci and oval cells. Similar levels of c-myc transcripts were detected in oval cells and basophilic hepatocytes generated by the uninitiated version of the protocol as were found in preneoplastic foci and oval cells during hepatocarcinogenesis. Whereas c-myc expression remained elevated in late neoplastic nodules and carcinomas, it gradually declined in both "remodelling" nodules and uninitiated livers. Our data indicate that c-myc expression is elevated during the undifferentiated stages of hepatocyte development. Furthermore, the data support the hypothesis that a critical early step in chemical hepatocarcinogenesis involves a block in the normal differentiation program of the hepatocytes.
Tumors produced by a chemically transformed rat liver epithelial (RLE) cell line and its single cell-derived clonal subpopulations demonstrate wide-ranging morphological presentations including carcinomas, sarcomas, "mixed epithelial-mesenchymal" tumors, and undifferentiated tumors [Am J Pathol 127:168-181, 1987]. To address the question of heterogeneity of tumors derived from transformed RLE cells, we have used recombinant retroviruses containing the following transforming oncogenes: v-raf (3611-MSV), v-raflv-myc (J2), v-myc (J5), and v-Ha-ras (pRNR16). All of the oncogenes, with the exception of v-myc (J5), were efficient transforming agents in the RLE cells. Tumors derived from the v-raf- and, to a lesser extent, those from v-Ha-ras-transformed RLE cells showed mixed epithelial-mesenchymal morphology, whereas the combination of v-raflv-myc (J2) consistently produced differentiated trabecular carcinomas. These data suggest that the lineage commitment of the RLE cells can be perturbed by a single transforming oncogene and that different tumor types derived from these cells may reflect the expression of a selective oncogene or a combination of oncogenes.
Orientation of ten water molecules bound strongly at the contact surface of the dihydrofolate reductase-methotrexate enzyme-inhibitor complex was determined theoretically. To optimize the orientation of the water molecules, a recent method based on a simple electrostatic model was applied. The electrostatic complementarity in the binary complex was investigated using the lock-and-key model, considering the effect of the water molecules as well. The strongly bound water molecules improve the electrostatic fit in the pteridine region of methotrexate. Their role in the benzoic amide and gamma-glutamate region is to decrease the internal energy by creating water bridges among remote polar sites making it possible to form H-bonds. Some modifications in the inhibitor structure were proposed for achieving greater inhibitor potency. The presumably enhanced effect is ascribed to the free energy gain in repelling the water molecules from the contact surface to the bulk of the solvent, and, in other cases, to internal energy decreases due to better electrostatic fit in the enzyme-inhibitor complex.
The expressions of albumin and alpha-fetoprotein (AFP) genes were studied in early preneoplastic liver lesions produced by the Solt-Farber protocol using "in situ" hybridization with single stranded RNA probes. In normal rat liver, albumin was expressed at a lower level in the centrilobular than in the periportal areas of the liver acinus, whereas the bile duct epithelium did not show any expression. Five weeks after initiation with diethylnitrosamine, islands of hepatocytes were present which showed heterogeneous expression of albumin and were surrounded by cells comprised of albumin negative hepatocytes and oval cells. gamma-Glutamyltranspeptidase positive foci of enzyme altered cells were located in albumin positive areas. Albumin expression gradually decreased in permanent nodules but increased in the hepatocytes outside the nodules during the first five months after initiation with diethylnitrosamine. Remodeling nodules, which were partly gamma-glutamyltranspeptidase and albumin positive, were also present. However, no consistent correlation was found between gamma-glutamyltranspeptidase positive and albumin negative areas during the first 5 months after initiation. Occasionally, cells showing an elevated expression of albumin were found in permanent nodules. These cells were located in the vicinity of oval type cells, which also showed a weak expression of albumin. AFP was expressed at high level in oval cells 5 weeks after the initiation. However, oval cells observed at later time points, either around the neoplastic nodules or inside the nodules showed only low expression of AFP. Hepatocytes in the enzyme-altered foci and in neoplastic nodules were always negative for AFP. The presence of strongly albumin positive cells inside the neoplastic nodules in close proximity to oval type cells suggests that these cells may be derived from primitive "stem-cell"-like oval cells.