Search PubMed⌕ Search

Biomedical subjects

W Gerok

Publications and source records attributed to W Gerok.

At least 181 records · Page 10Linked to original sources
PubMed1988

Astrocytes synthesize and secrete alpha 2-macroglobulin: differences between the regulation of alpha 2-macroglobulin synthesis in rat liver and brain.

alpha 2-Macroglobulin (alpha 2M) is an important proteinase inhibitor both in the blood and in the interstitial space of many mammalian species. Recently, occurrence of alpha 2M in human and fetal rat brain has been reported. However, its cellular origin remained obscure. Here it will be shown that astroglial cells cultured from newborn rats synthesize and secrete alpha 2M. In addition to astrocyte primary cultures a rat astrocytoma cell line, C6-cells, also synthesize and secrete alpha 2M. In contrast to hepatocytes of the adult rat, where alpha 2M is expressed as an acute-phase protein and where glucocorticoids and monocyte-derived factors are required for its synthesis, alpha 2M synthesis in astrocytes of newborn rats is independent from both. It is therefore concluded that expression of alpha 2M is differently regulated in the liver of the adult rat and fetal or neonatal brain.

Animals↗
PubMed1988

Endotoxin abolishes the induction of alpha 2-macroglobulin synthesis in cultured human monocytes indicating inhibition of the terminal monocyte maturation into macrophages.

Monocytes were prepared from human blood and allowed to differentiate into macrophages in vitro. Synthesis and secretion of the potent proteinase inhibitor alpha 2-macroglobulin is strongly induced during maturation of monocytes into macrophages establishing alpha 2-macroglobulin as a differentiation marker protein. When the monocytes were incubated with endotoxin (S. typhi) in a concentration as low as 100 ng/ml, induction of alpha 2-macroglobulin synthesis was completely abolished indicating impaired monocyte/macrophage differentiation by lipopolysaccharides (LPS). In contrast to alpha 2-macroglobulin, synthesis of alpha 1-proteinase inhibitor in mononuclear phagocytes was stimulated by endotoxin.

Cell Differentiation↗
PubMed1988

Clinical significance of abnormalities of the gastrointestinal tract detected by abdominal ultrasound.

In order to define the clinical significance and the need for further clinical work-up in patients where abnormalities of the stomach or bowel are found by ultrasound, we performed a prospective study on 100 patients with such findings. Of all patients, 35% were found to have a malignant tumor, 73% had a diagnosis as made by reference methods which was probably (18%) or definitively (55%) related to the US finding. Eighteen percent had definitive false positive findings, in 9% no final diagnosis was obtained. Thus, a positive predictive value of 80% was calculated for the US finding of a mass or a target sign related to bowel or stomach in US. The positive predictive value was lowest for target signs related to the bowel (75%) and highest for bowel conglomerates (100%). Patients with target signs of the stomach, bowel conglomerates, or masses were more likely to have malignant disorders (72%) than those with target signs related to the bowel (16%). We conclude from this study that the ultrasound finding of a target sign or a mass related to stomach or bowel has a high clinical relevance and should in any case worked up by appropriate investigations when clinical consequences are possible.

Digestive System↗
PubMed1988

Scintigraphic assessment of bowel involvement and disease activity in Crohn's disease using technetium 99m-hexamethyl propylene amine oxine as leukocyte label.

Using a novel labeling technique with technetium 99m-hexamethyl propylene amine oxine, we studied 29 patients with known or suspected Crohn's disease. Technetium 99m-hexamethyl propylene amine oxine leukocyte scanning (99mTc scan) was prospectively compared with the results of independently performed radiologic, endoscopic, and histologic examinations, and with findings at surgery, to assess the clinical usefulness of this technique to localize inflammatory lesions. In addition, uptake of technetium 99m-hexamethyl propylene amine oxine in the bowel was graded by comparing it with the uptake in liver and bone marrow and correlating this with established parameters of disease activity. The viability of homologous labeled leukocytes was greater than 95%. Less than 5% of lymphocytes were found in the final preparation. It was found that 45% +/- 12% of the label was bound to granulocytes, and 98% of the unbound label was washed off before reinjection. The results of 99mTc scan revealed a good correlation with those of barium enema (r = 0.880, p less than 0.001), of endoscopy/surgery (r = 0.983, p less than 0.001), and of all combined reference methods (r = 0.981, p less than 0.001). Activity as determined by 99mTc scan was weakly correlated with the results of Crohn's disease activity index (r = 0.559, p less than 0.01), van Hees index (r = 0.606, p less than 0.01), and erythrocyte sedimentation rate (r = 0.456, p less than 0.05) in 24 patients with proven Crohn's disease. The correlation was improved when the 99mTc scan was compared with a combination of these activity parameters and C-reactive protein (r = 0.781, p less than 0.001). Extraintestinal manifestations (joints) and complications (cholecystitis) were also identified correctly by the 99mTc scan. The study demonstrates that leukocyte scanning with technetium 99m-hexamethyl propylene amine oxine as a label can reliably assess the location and, to a lesser degree, activity of Crohn's disease. This technique is more convenient and provides images far superior to those produced by indium 111-labeled leukocyte scanning.

Adolescent↗
PubMed1988

Duck hepatitis B virus: DNA polymerase and reverse transcriptase activities of replicative complexes isolated from liver and their inhibition in vitro.

The duck hepatitis B virus (DHBV)-associated activities of reverse transcriptase and DNA polymerase and their inhibition in vitro were studied. Replicative complexes (RCs) were isolated from DHBV-infected liver by gel chromatography followed by sucrose gradient centrifugation. The RCs were detected by dot blot hybridization, using radiolabeled cloned DHBV DNA as a probe, and by the incorporation of 32P-TTP in the presence of dATP, dCTP, dGTP, and Mg2+ (endogenous DNA polymerase activity). The endogenous DNA polymerase activity associated with RCs was further studied using exogenous templates: reverse transcriptase and DNA polymerase activities were demonstrated using as substrates 32P-TTP and poly(rA) p(dT)12 or poly(dA) p(dT)12-18, respectively. Both activities were biochemically characterized. Their inhibition by various antiviral agents was studied in vitro: actinomycin D, ara-ATP, aphidicolin, suramin, chloroquin, and phosphonoformate. Among these, suramin, chloroquin, phosphonoformate, and ara-ATP were shown to be potent inhibitors of viral reverse transcriptase and DNA polymerase. Studies are now in progress to establish their antiviral activity in vivo.

Animals↗
PubMed1988

Transport systems for amphipathic compounds in normal and neoplastic hepatocytes.

Photoaffinity labeling of plasma membrane subfractions from liver and of intact liver tissue with a photolabile bile salt derivative, the sodium salt of (7,7-azo-3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-aminoethanesulfonic acid, revealed that the hepatobiliary transport of bile salts is accomplished by transport systems different for sinusoidal uptake and canalicular secretion. Polypeptides with apparent Mr values 54,000 and 48,000 interact with bile salts at sinusoidal membrane, whereas a polypeptide with an apparent Mr of 100,000 is involved in bile salt secretion through the canalicular membrane. Photoaffinity labeling with photolabile derivatives of uncharged and cationic compounds provided evidence that the sinusoidal membrane polypeptides exhibit a broad binding specificity. Photoaffinity labeling studies and kinetic studies suggest that hepatic uptake of different amphipathic anions, uncharged compounds and even of cations is mediated by the sinusoidal transport systems which are involved in the uptake of bile salts. Relatively little is known about the specificity of the canalicular bile salt transport system. The fluorescent bile salt derivative, the sodium salt of (N-[7-(4-nitrobenzo-2-oxa-1,3-diazol)]-3 beta-amino-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-aminoethanesulfonic acid, is readily taken up into the hepatocytes of all acinar zones and may be used for the evaluation of the functional state of bile salt transport by fluorescence microscopy. Fluorescent microscopic studies with the fluorescent bile salt derivative showed that ascites hepatoma AS 30D cells do not have the ability to take up bile salts and demonstrated the absence of hepatobiliary bile salt transport in the solid Morris hepatoma 7777. Photoaffinity labeling studies revealed that in both tumor cell models, in hepatoma AS 30D and in Morris hepatoma 7777, the plasma membranes were devoid of the polypeptides having affinities to bile salts and amphipathic cations. A slight labeling of bile salt binding membrane polypeptides in plasma membranes from Morris hepatomas 9618A and TC 5123 opens the possibility to study transport in neoplastic hepatocytes.

Animals↗
PubMed1988

Proteases and antiproteases related to the coagulation system in plasma and ascites. Prediction of coagulation disorder in ascites retransfusion.

To improve the ability to predict the occurrence of coagulation disorders in ascites retransfusion and, in addition, to better define the nature of the coagulation disorder, several proteases and antiproteases were analyzed in ascites and plasma before ascites retransfusion in 17 patients. Plasminogen, alpha 2-antiplasmin, antithrombin III, and fibrin(ogen) degradation products in ascites were significantly altered in patients who later developed abnormal coagulation as compared to those who did not. Only plasminogen and alpha 2-antiplasmin in ascites achieved a sufficient predictive value for the occurrence of coagulation abnormalities. The pattern of the coagulation abnormalities observed strongly suggests fibrinolysis induced by the infusion of plasminogen activators as the cause of the coagulation disorder in ascites retransfusion procedures.

Antithrombin III↗
PubMed1988

Increased prostaglandin E release and tumor cytostasis by resident Kupffer cells during Listeria monocytogenes infection.

Liver macrophages isolated from Listeria monocytogenes-infected mice were studied for their functional capacities in vitro. Spontaneous release of prostaglandin E and tumor cytostatic activity by liver macrophages of infected mice were markedly enhanced when compared to controls. Irradiated mice showing no increase in the number of their liver macrophages after Listeria monocytogenes infection, in contrast to solely infected mice, nevertheless demonstrated comparable activities. Our data suggest that radioresistant liver macrophages, most probably resident Kupffer cells, can be activated during in vivo infection to express enhanced effector functions.

Animals↗
PubMed1988

Ammonia and glutamine metabolism in human liver slices: new aspects on the pathogenesis of hyperammonaemia in chronic liver disease.

Ammonia and glutamine metabolism was studied in slices from normal, fatty and cirrhotic human livers. The liver disease was evaluated by histological examination. With respect to ammonia removal, urea and glutamine synthesis in human liver represent low and high affinity systems with k0.5(NH4+) values of 3.6 and 0.11 mM, respectively. Compared with normal control livers, cirrhotic livers showed a decreased glutamine synthesis from NH4Cl by about 80%. The same was true for urea synthesis. Conversely, flux through hepatic glutaminase was increased in cirrhosis 4-6-fold. These changes in hepatic glutamine and ammonia metabolism were observed regardless of whether reference was made to liver wet weight, DNA or protein content. Acetazolamide inhibited urea synthesis in cirrhotic liver slices by about 50%, indicating that mitochondrial carbonic anhydrase is required for urea synthesis also in cirrhosis. There was a significant correlation between the in-vitro determined capacity for urea synthesis from NH4Cl and the in-vivo determined plasma bicarbonate concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1988

Latent hepatitis B virus infection with full-length viral genome in a patient serologically immune to hepatitis B virus infection.

The presence, state, physical structure and cellular localization of hepatitis B virus (HBV) DNA were investigated in a patient with hepatitis B surface antigen (HBsAg)-negative chronic liver disease. HBV serology was positive for antibodies to hepatitis B core antigen (anti-HBc), to hepatitis B e antigen (anti-HBe) and to HBsAg (anti-HBs); no HBV DNA was detectable in serum. Southern blot analyses of DNA extracted from the liver demonstrated free monomeric HBV DNA as two distinct species: a predominant species of fully double-stranded relaxed circular molecules and a minor species of linear molecules of 3.2 kilobase pairs (kbp) length. Restriction enzyme analyses identified the HBV genome as HBsAg subtype adw2. Cell fractionation studies further revealed that the free viral DNA species were localized exclusively in liver cell nuclei. These findings in a patient serologically immune to HBV infection demonstrate that in hepatocytes HBV can establish a latent infection, characterized by the extrachromosomal presence of a full-length viral genome without production of infectious virus or synthesis of viral antigens.

Aged↗
PubMed1988

Effects of leukotrienes and the thromboxane A2 analogue U-46619 in isolated perfused rat liver. Metabolic, hemodynamic and ion-flux responses.

1) Addition of leukotriene C4 to isolated perfused rat liver led to a stimulation of hepatic glucose output, a slight decrease of 14CO2 production from [1-14C] glutamate, an increase of portal pressure and an inhibition of hepatic oxygen uptake. Withdrawal of leukotriene C4 caused a transient further stimulation of hepatic glucose output. 2) These effects were accompanied by a slow net Ca2+ release from the liver, which was not completed within 8 min. Following leukotriene withdrawal there was a further Ca2+ release for about 1 min superimposing a slow reuptake of Ca2+ of about 10 min duration. 3) Leukotriene C4 induced a characteristic biphasic K+ release from the liver. Withdrawal of the leukotriene resulted in a further net K+ release for about 4 min, being followed by a K+ reuptake over more than 10 min. 4) Effects comparable to those induced with leukotriene C4 (20nM) were obtained with leukotriene D4 (20nM), were as leukotriene B4 and E4 (20nM each) were much less effective. 5) The thromboxane A2 analogue U-46619 produced ionic, metabolic and hemodynamic responses similar to leukotriene C4; however, when given at concentration yielding a comparable glucose release, the thromboxane analogue was much more vasoactive than leukotriene C4. The thromboxane A2 receptor antagonist BM-13.177 (20 microM) blocked the metabolic, hemodynamic and ion flux responses to U-46619 almost completely, but had no effect on the response to leukotriene C4. 6) Each, leukotrienes, U-46619 and UTP led to an inhibition of hepatic oxygen uptake. The extent of inhibition of oxygen uptake induced by these compounds was not exclusively explained by their effects on hepatic circulation: a 30% inhibition of oxygen uptake by leukotriene C4, U-46619 or UTP was accompanied by increases of the portal pressure of 4.9 +/- 0.4 (481 +/- 39 Pa) (n = 7), 16.0 +/- 1.9 (1570 +/- 186 Pa) (n = 7) or 11.4 +/- 0.4 (1118 +/- 39 Pa) (n = 13) cm H2O, respectively. 7) The data show that leukotrienes and possibly also thromboxanes are potent regulators of hepatic metabolism and hemodynamics, probably acting by a Ca2+ mobilizing mechanism and involving different receptor systems. The response of perfused liver to these compounds is qualitatively similar to that obtained with extracellular UTP, but different to that with prostaglandins, extracellular ATP or phenylephrine. The data further support the view that eicosanoids are important modulators of hepatic metabolism and point to a complex regulatory interaction between hepatic parenchymal and non-parenchymal cells.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Regulation of interleukin-6 expression in cultured human blood monocytes and monocyte-derived macrophages.

A culture system that allows human blood monocytes to differentiate into macrophages in vitro was used to study B-cell stimulatory factor-2/interleukin-6 (interferon-beta 2/26 kd protein) expression in mononuclear phagocytes. Using B-cell stimulatory factor-2 (BSF-2) cDNA and a polyclonal, monospecific antibody directed against human BSF-2, we find that strong interleukin-6 (IL-6) expression is initiated in cultured monocytes on stimulation with endotoxin. Maximally induced monocytic BSF-2/IL-6 synthesis (1% to 2% of total proteins secreted by monocytes) is more than ten times stronger than in terminally differentiated macrophages (approximately 0.1% of total secretory proteins). BSF-2/IL-6 mRNA was detectable as early as one hour after stimulation with endotoxin, reaching maximum levels three hours after stimulus. Interleukin-1 (IL-1) was able to stimulate IL-6 synthesis in monocytes, but not in macrophages. Tumor necrosis factor, interferon-gamma and interleukin-2 (IL-2) had no effect on IL-6 synthesis in monocytes or macrophages. We found five molecular weight forms of BSF-2/IL-6 to be secreted by monocytes of 21.5 kd, 23.5 kd, 24 kd, 26 kd, and 28 kd apparent molecular weight. The 26 kd and 28 kd forms were found to represent N-glycosylated molecules, which were not detectable on treatment of the cells with the N-glycosylation inhibitor tunicamycin. The 21.5 kd, 23.5 kd, and 24 kd BSF-2/IL-6 forms were unaffected by tunicamycin treatment. We conclude from our data that cells of the mononuclear phagocyte lineage are one of the main sites of BSF-2/IL-6 (interferon-beta 2/26 kd protein/HSF) synthesis.

Cell Differentiation↗
PubMed1987

Hepatocyte heterogeneity in response to extracellular ATP.

1. The metabolic and hemodynamic effects of extracellular ATP in perfused rat liver were compared during physiologically antegrade (portal to hepatic vein) and retrograde (hepatic to portal vein) perfusion. ATP in concentrations up to 100 microM was completely hydrolyzed during a single liver passage regardless of the perfusion direction. 2. The ATP(20 microM)-induced increases of glucose output, perfusion pressure and ammonium ion release seen during antegrade perfusions were diminished by 85-95% when the perfusion was in the retrograde direction, whereas the amount of Ca2+ mobilized from the liver was decreased by only 60%. The maximal rate of initial K+ uptake following ATP was dependent on the amount of Ca2+ mobilized regardless of the direction of perfusion. In the presence of UMP (1 mM), an inhibitor of ATP hydrolysis by membrane-bound nucleotide pyrophosphatase, the effect of the direction of perfusion on the glycogenolytic response to ATP (20 microM) was largely diminished. 3. For a maximal response of glucose output, Ca2+ release and perfusion pressure to extracellular ATP, concentrations of about 20 microM, 50 microM and 100 microM were required during antegrade perfusion, respectively. These maximal responses could also be obtained during retrograde perfusion, but higher ATP concentrations were required (120 microM, 80 microM, above 200 microM, respectively). 4. 14CO2 production from [1-14C]glutamate which occurs predominantly in the perivenous hepatocytes capable of glutamine synthesis was stimulated by extracellular ATP (20 microM); it was only slightly affected by the direction of perfusion. In antegrade perfusions, ATP (20 microM) increased 14CO2 production from 88 to 162 nmol g-1 min-1, compared to an increase from 91 to 148 nmol g-1 min-1 in retrograde perfusion. 5. The data are interpreted to suggest that (a) extracellular ATP is predominantly hydrolyzed by a small hepatocyte population located at the perivenous outflow of the acinus; (b) glycogenolysis to glucose is predominantly localized in the periportal area; (c) contractile elements (sphincters) exist near the inflow of the sinusoidal bed; (d) a considerable portion of the Ca2+ mobilized by ATP is derived from liver cells that do not contribute to hepatic glucose output.

Adenosine Triphosphate↗
PubMed1987

[Percutaneous transhepatic cholangioscopy. A new method for the diagnosis of bile duct malignancies].

Percutaneous transhepatic cholangioscopy combines the advantages of endoscopic and radiological examinations. It makes it possible to assess the intraluminal spread of bile duct disease as well as histological and cytological examination of biopsies obtained under vision. Eight PTCs were performed without complication in seven patients with cancer of the bile duct. In four, the histology and extent of the tumour was defined endoscopically before any surgical intervention. In three others the results of treatment were objectified. A flexible choledochoscope, as used intraoperatively, was employed (CHF-P10). A stepwise dilatation of the percutaneous access-route was undertaken in several sessions in order to avoid bleeding complications. The procedure is done without general anaesthesia.

Adenocarcinoma↗
PubMed1987

Repression of alpha 2-macroglobulin and stimulation of alpha 1-proteinase inhibitor synthesis in human mononuclear phagocytes by endotoxin.

Mononuclear phagocytes are a bone-marrow-derived subgroup of white blood cells which circulate as monocytes and, after differentiation into macrophages, become resident in many tissues. By synthesizing the important proteinase inhibitors alpha 2-macroglobulin and alpha 1-proteinase inhibitor mononuclear phagocytes contribute to the control of proteolysis both in blood and tissues. Applying a culture system which enables human blood monocytes to differentiate into macrophages in vitro, synthesis of alpha 2-macroglobulin and alpha 1-proteinase inhibitor was studied. The normal course of monocyte-macrophage maturation is accompanied by a strong increase of specific alpha 2-macroglobulin synthesis and a concomitant slight decrease of alpha 1-proteinase inhibitor. alpha 2-Macroglobulin can be designated as a marker protein of the monocyte/macrophage differentiation. Endotoxin (Salmonella typhi) in a concentration as low as 100 ng/ml strongly represses alpha 2-macroglobulin synthesis both in monocytes and macrophages. Furthermore, endotoxin completely abolishes the induction of alpha 2-macroglobulin synthesis during the course of normal monocyte in vitro cultivation, indicating that endotoxin is a strong inhibitor of the monocyte-macrophage maturation. In contrast to alpha 2-macroglobulin, alpha 1-proteinase inhibitor synthesis is strongly stimulated by endotoxin in monocytes as well as in macrophages.

Blood Proteins↗