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Biomedical subjects

G Acs

Publications and source records attributed to G Acs.

At least 55 records · Page 3Linked to original sources
PubMed1992

[Hand fractures and epiphyseal injuries in childhood].

Anatomic features of the hand in childhood are presented that are responsible for the types of certain injuries. On the basis of the data in the literature and of the authors' own experience of 92 cases the main points of the diagnosis and therapy of metacarpal and phalanx fractures are summarized. The possibility of finger-replantation is also mentioned. Their statements are illustrated by their own cases. In order to recognize late growth disturbances, the necessity of the follow up is emphasized.

Bone Nails↗
PubMed1992

[Liver specific gene expressions in human fetal hepatocyte culture].

The authors studied the function of human fetal liver cell--on level of DNA and gene regulation--by methods of molecular biology. Experiments were done under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee. They conclude that human fetal liver culture may serve as a suitable in vitro modell for study of the liver specific gene expressions. They found that cultured human fetal liver cells from second trimester express albumin and AFP. They demonstrate that fetal hepatocytes--like adult hepatocytes--respond to the inflammatory mediators, IL-1, IL-6 and TNF, by induction of CRP and alpha-1-Ach expression and regression of albumin synthesis proving the ability of fetal hepatocytes to produce an acute phase response.

Autoradiography↗
PubMed1992

Specific binding to protein kinase C by ingenol and its induction of biological responses.

We have examined the ability of ingenol to bind to and activate protein kinase C and to induce similar responses to the phorbol esters in biological systems. The rationale was that ingenol possesses the critical functionalities of the phorbol ester pharmacophore with the exception of the hydrophobic domain; it might therefore possess weak potency, although previous reports had indicated that ingenol was biologically inactive. Our data demonstrate that ingenol indeed binds to protein kinase C with a Ki of 30 microM and activates the enzyme. In addition, ingenol was biologically active in 3 separate cell systems, showing effects similar to the phorbol esters on morphological change, cell-cell communication, epidermal growth factor binding, arachidonic acid metabolite release, and ornithine decarboxylase activity. The 50% effective concentration values for the biological activity of ingenol were between 30 microM and 1 mM, varying somewhat with the cell system and type of response. The biological activity of ingenol in general supports the proposed models of the phorbol ester pharmacophore and imposes additional experimental constraints that the modeling must satisfy.

Animals↗
PubMed1992

The mechanism of inhibition of hepatitis B virus replication by the carbocyclic analog of 2'-deoxyguanosine.

The carbocyclic analog of deoxyguanosine inhibits hepatitis B virus replication by greater than 95% in the hepatitis B virus-producing cell line (2.2.15) as monitored by decreases of secreted hepatitis B virus DNA, hepatitis B virus polymerase activity and intracellular episomal hepatitis B virus DNA. Transcription of hepatitis B virus RNA from chromosomally integrated hepatitis B virus DNA was unaffected. Radioactive carbocyclic 2'-deoxyguanosine was directly phosphorylated within the 2.2.15 cells and was incorporated exclusively into DNA. In contrast, radioactive deoxyguanosine was presumably metabolized through the "salvage" pathway in which the guanine was primarily incorporated into cellular RNAs. The rate of incorporation of carbocyclic 2'-deoxyguanosine in 2.2.15 cells was similar to that in the parental cell line (HepG2), which does not contain hepatitis B virus sequences. Greater than 90% of the analog was present at internal sites within the DNA, indicating that the analog did not function as a DNA chain terminator. Kinetic analysis of the Km and Ki of dGTP and carbocyclic 2'-deoxyguanosine 5'-triphosphate, respectively, using both hepatitis B virus polymerase and DNA polymerase delta indicated that the analog is a competitive inhibitor for dGTP. Although both polymerases had similar Km's for dGTP, the Ki for carbocyclic 2'-deoxyguanosine 5'-triphosphate was about 6 times lower using the hepatitis B virus polymerase. This would indicate that, at low concentrations of intracellular carbocyclic 2'-deoxyguanosine 5'-triphosphate, the hepatitis B virus polymerase would be preferentially inhibited. We propose this to be the mechanism acting to inhibit preferentially hepatitis B virus replication in the tissue culture cells.

Antiviral Agents↗
PubMed1992

[Experience with the surgical management of childhood fractures and epiphyseal injuries].

Authors analyse 1792 fractures in children, treated during 10 years in their Department and distributed in age groups. They take the part of conservative treatment of the majority, about two third, of fractures in childhood. They consider as operative indication certain forms of epiphyseal injuries, the dislocated intraarticular fractures, the unstable fractures, certain cases of polytrauma and the open fractures.

Adolescent↗
PubMed1992

[Experience with the management of childhood diaphyseal fractures].

Author reports on experiences gained during 10 years the diaphyseal fractures in childhood. Whereas certain types of fracture near to the joints have a generally accepted absolute operative indication, the surgery in diaphyseal fractures is rarely held to be indicated. Osteosynthesis was performed in 18 per cent of all cases. Surgery is thought to be indicated in open fractures, in fractures that cannot be reduced or that are unstable, in polytrauma and in bilateral cases. In closed fractures plate osteosynthesis, in severe open fractures the fixateur externe was found to be the best solution. In certain cases Kuntscher nailing of the femur, medullary splinting of the lower arm or diafixation of the lower leg are performed in older children.

Adolescent↗
PubMed1991

[Classification of the condition of accidental injuries in children by grading].

The authors give a brief survey of the point system used in the classification of injuries. They present the evaluation of the polytraumatic and seriously injured patients of their department accept during a period of two and half years. The results are compared with the material of children recorded during a five years period. They describe the point system used in the classification of children's injuries (PTS) and point out that the TS and ISS system used with adult patients are suitable for numerical determination of the condition of injured children.

Accidents↗
PubMed1991

Human fetal hepatocytes respond to inflammatory mediators and excrete bile.

Under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee, primary hepatocyte cultures were prepared from second-trimester fetal liver specimens. We have shown for the first time that fetal hepatocytes have the capacity to produce an acute-phase response on treatment with inflammatory mediators. Addition of interleukin-6 to the cultures resulted in strong induction of C-reactive protein and alpha-1-antichymotrypsin expression, whereas albumin expression was repressed. In contrast to interleukin-6, transforming growth factor-beta did not induce C-reactive protein expression. However, as in adult hepatocytes, fetal cells responded to transforming growth factor-beta by reduced albumin synthesis. We were able to show by virtue of fluorescein excretion into sealed clefts that fetal hepatocytes have the functional capacity to form bile. Our findings indicate that second-trimester hepatocytes can be regarded as fairly mature liver cells.

Acetylcholine↗
PubMed1991

Evaluation of the effectivity of Nitromint spray in comparison with sublingual tablet in emergency and ambulance practice.

The effect of Nitromint sublingual tablet and Nitromint aerosol (EGIS) has been studied in ambulance practice. Both drug forms relieved or controlled the complaints and symptoms, and proved to be effective in a great number of cases. Due to it's easier storage and easier applicability the aerosol is more advantageous than the sublingual tablet. Occasionally the simultaneous use of the two products is also beneficial. Supposedly the indication field of nitroglycerin will be extended in the near future and Nitromint preparations will be used in oxyology also for controlling other clinical conditions in which smooth muscle spasm has a major role.

Administration, Sublingual↗
PubMed1990

[The role of interleukin-1 beta in the regulation of liver-specific gene expression in human hepatoblastoma cells].

The authors studied the function of liver cells--on level of DNA and gene regulation--by methods of molecular biology. They found that treating human hepatoma (Hep G2) cells with interleukin-1 (IL-1) leads to the induction of alpha-1-acidglycoprotein (AGP) and complement 3 (C3) mRNA synthesis, and to a concomitant downregulation of albumin (alb), alpha-fetoprotein (AFP) and alpha-2-macroglobulin (alpha 2M) mRNA synthesis. Levels of specific mRNA were measured by Northern-blot analysis. They conclude that Hep G2 cells may serve as a suitable in vitro model for study of the liver specific gene expression, and IL-1 is one of the mediators of these gene control. The regulation is pretranslational as the direction of change in specific mRNA corresponds to the changes in synthesis of the respective proteins.

Blotting, Northern↗
PubMed1990

A nude mouse model for the in vivo production of hepatitis B virus.

Hepatitis B virus genome-transfected HepG2 cells (2.2.15 cells) inoculated into nude mice produced tumors within 2-8 wk. Dane particles, hepatitis B virus deoxyribonucleic acid polymerase activity, hepatitis B surface antigen, and hepatitis B e antigen were detected in the serum, and 36% of mice developed antibodies to hepatitis B core antigen. In the tumors, hepatitis B surface, core, and e antigens were observed by electron microscopy and immunoenzymatic techniques. In-situ hybridization and Southern blot analysis showed hepatitis B virus deoxyribonucleic acid in the tumor. Tumors could be propagated by injection of minced tumor tissue or of a tumor-derived cell line. Liver of tumor-bearing mice as well as sera and tissues of mice inoculated with control cell lines did not show hepatitis B virus genome or viral markers. Tumors induced by both 2.2.15 and nontransfected HepG2 cells exhibited myc oncogene protein and various hepatoma-associated antigens (alpha-fetoprotein, alpha-1-antitrypsin, alpha-1-antichymotrypsin, carcinoembryonic antigen, cytokeratin), suggesting that viral formation does not interfere with expression of these antigens. This experimental model will be helpful to study the effect of drugs on in-vivo hepatitis B virus replication and viral antigen expression.

Animals↗
PubMed1990

Selective inhibition of hepatitis B virus and human immunodeficiency virus sequence-promoted gene expression by cotransfected poly(I):poly(C).

The transient expression of hepatitis B virus (HBV) surface and "eJ" antigens caused by transfection of human hepatoblastoma HepG2 cells with HBV DNA was markedly inhibited by cotransfection with poly(I):poly(C). Cotransfection with poly(I):poly(C) also inhibited the expression of bacterial chloramphenicol acetyltransferase (CAT) gene which was under the control of either the HBV core promoter or the human immunodeficiency virus (HIV-1) long terminal repeat. This inhibition was much more pronounced on the expression of HBV-promoted CAT than HIV-promoted CAT. The uptake of reporter plasmid was not affected by cotransfected poly(I):poly(C). The inhibition was found to be at the steady-state CAT mRNA level and appeared to be specific for HBV and HIV regulatory sequences since CAT expression directed by other viral and cellular regulatory sequences was not inhibited. Cotransfection with a mixture of equal amounts of poly(I) and poly(C) had similar inhibitory effects whereas cotransfection with poly(l) or poly(C) alone, or other double-stranded ribo- or deoxyribonucleotides, did not have such strong effects. The addition of poly(l):poly(C) to the culture medium of cells transfected with these reporter plasmids caused little inhibition. Transfection with poly(l):poly(C) induced a minimal amount of intracellular interferon-alpha in HepG2 cells which may be involved in selective inhibition of HBV-and HIV-1-directed gene expression. 2-Aminopurine, an inhibitor of double-stranded RNA activated protein kinase known to block interferon gene induction by poly(l):poly(C), partially reversed the poly(l):poly(C)-induced inhibitory effect on HBV-CAT expression.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Regulation of interleukin 6 receptor expression in human monocytes and monocyte-derived macrophages. Comparison with the expression in human hepatocytes.

IL-6 is a cytokine with pleiotropic biological functions, including induction of the hepatic acute phase response and differentiation of activated B cells into Ig-secreting plasma cells. We found that human peripheral blood monocytes express the IL-6-R, which is undetectable on the large majority of lymphocytes of healthy individuals. Stimulation of monocytes by endotoxin or IL-1 causes a rapid downregulation of IL-6-R mRNA levels and a concomitant enhancement of IL-6 mRNA expression. IL-6 itself was found to suppress the IL-6-R at high concentrations. A gradual decrease of IL-6-R mRNA levels was observed along in vitro maturation of monocytes into macrophages. We show that downregulation of IL-6-R mRNA levels by IL-1 and IL-6 is monocyte specific, since IL-6-R expression is stimulated by both IL-1 and IL-6 in cultured human primary hepatocytes. Our data indicate that under noninflammatory conditions, monocytes may play a role in binding of trace amounts of circulating IL-6. Repression of monocytic IL-6-R and stimulation of hepatocytic IL-6-R synthesis may represent a shift of the IL-6 tissue targets under inflammatory conditions.

Blotting, Northern↗
PubMed1989

Regulation of interleukin-6 receptor expression in human monocytes and hepatocytes.

Human blood monocytes normally express the interleukin-6 receptor. Treatment of cultured monocytes with endotoxin, interleukin-1 beta, or interleukin-6 results in a decrease in interleukin-6 receptor mRNA levels. Glucocorticoids aso cause a drop in monocytic interleukin-6 receptor mRNA levels. We also found interleukin-6 receptor expression in cultured human hepatocytes, but in contrast to monocytes, where interleukin-6 receptor mRNA is presented by the ligand and by interleukin-1, treatment of hepatocytes with interleukin-6 or interleukin-1 resulted in increased interleukin-6 receptor mRNA levels. Induction of interleukin-6 receptor mRNA in hepatocytes was less pronounced when glucocorticoids were omitted from the culture medium. We conclude that during noninflammatory homeostasis, blood monocytes are involved in binding of trace amounts of circulating interleukin-6. During inflammatory events, the main target of interleukin-6 may be changed from the monocytic population not only to activated B-cells, but also to the hepatocytes.

Acute-Phase Reaction↗
PubMed1989

Tumor necrosis factor-alpha induces a kappa B sequence-specific DNA-binding protein in human hepatoblastoma HepG2 cells.

Tumor necrosis factor-alpha is an inducer of acute-phase protein synthesis in liver cells. The mechanism by which tumor necrosis factor-alpha alters gene expression in these cells is largely unknown. In this study, we demonstrate that tumor necrosis factor-alpha stimulates human immunodeficiency virus-1 long terminal repeat-promoted gene expression in the human hepatoblastoma HepG2 cell line and increased binding of trans-activating factors to kappa B (kappa B) DNA sequences. In contrast to lymphocytic cells where the nuclear factors recognizing the kappa B sequences are activated by both tumor necrosis factor-alpha and phorbol-12-myristate-13-acetate through a posttranslational mechanism, in HepG2 cells phorbol-12-myristate-13-acetate does not activate these factor(s), and de novo protein synthesis seems to be required in HepG2 cells for gene activation by tumor necrosis factor-alpha.

Base Sequence↗
PubMed1989

Inhibition of the replication of hepatitis B virus by the carbocyclic analogue of 2'-deoxyguanosine.

We report that treatment of 2.2.15, a human hepatoblastoma-derived cell line in which hepatitis B virus is actively replicating, with the carbocyclic analogue of 2'-deoxyguanosine [Shealy, Y. F., O'Dell, C. A., Shannon, W. M. & Arnett, G. (1984) J. Med. Chem. 27, 1416-1421] resulted in the nearly complete cessation of viral replication, as monitored by the absence of both intracellular episomal and secreted viral DNAs and by the absence of viral DNA polymerase activity. The drug was nontoxic in concentrations up to 200 times the minimum effective inhibitory concentration.

Antiviral Agents↗
PubMed1989

Complementation of recombinant baculoviruses by coinfection with wild-type virus facilitates production in insect larvae of antigenic proteins of hepatitis B virus and influenza virus.

We describe the coinfection of insects with wild-type and recombinant baculoviruses in which the polyhedrin gene promoter is used to express hepatitis B virus envelope protein (hepatitis B virus surface antigen; HBsAg) or influenza A virus neuraminidase (NA). Viruses were administered per os to larvae of the cabbage looper, Trichoplusia ni, causing an infection that within 5 days resulted in the production of approximately 0.15 mg of HBsAg per insect, representing 1.5% of the total extracted protein, or approximately 2.8 mg of NA per insect, representing 28% of the total extractable protein. The HBsAg and NA produced by infected larvae were purified from insect lysates. These proteins were antigenic as determined by conformation-dependent immunoassays. The NA was enzymatically active with conventional substrates. The method of infection described allows genetic complementation by wild-type virus of recombinant viruses lacking the polyhedrin gene essential for infection per os and has implications for the high-yield production in insect larvae of other recombinant proteins of baculoviruses.

Animals↗