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Biomedical subjects

W Gerok

Publications and source records attributed to W Gerok.

At least 217 records · Page 12Linked to original sources
PubMed1987

[Role of glycoproteins in the pathogenesis of peptic ulcer].

Glycoproteins are major constituents of the two-component mucous barrier: glycoproteins of the mucin-type rich in carbohydrate groups form the viscoelastic mucous gel of the mucosa, oligosaccharides of glycoproteins and glycosphingolipids embedded into the plasma membrane form the glycocalyx of the epithelial cell surface. Both structures are thought to play major roles in protecting gastric mucosa against luminal acid and proteases. This assumption is supported by experimental evidence for mucus glycoproteins, however is largely hypothetical for cell surface glycoproteins. Reports that biosynthesis of mucus glycoproteins is decreased during gastric ulceration, while breakdown is enhanced indicate that disorders of glycoprotein biosynthesis and degradation may contribute to the pathogenesis of peptic ulcer disease. The molecular mechanisms responsible for the observed alterations, however, are unknown. Possible alterations of glycoprotein metabolism that may occur at different stages of biosynthesis and degradation are discussed.

Animals↗
PubMed1987

Value and limitations of abdominal ultrasound in tumour staging--liver metastasis and lymphoma.

Real time ultrasound findings in 137 patients with proven or suspected liver metastasis and 51 patients with suspected malignant lymphoma were analyzed in order to define the accuracy of this method in tumour staging procedures. Sensitivity of liver metastasis was low (54.4%), while specificity (92.0%) and negative predictive value (95.8%) were good. Sensitivity for malignant lymphoma was better (84.6%), but specificity was less satisfactory (72.0%). Accuracy was dependent of the type of the primary tumour, bronchial carcinoma resulting in a very poor detection of liver metastases and suspected metastatic lymphoma leading to a large number of false positive results. We conclude from our data that only positive ultrasound findings of liver metastases or multiple lymphoma and probably a negative examination of the liver in patients with colonic carcinoma are sufficiently reliable to be used for therapeutic decisions in patients with malignant diseases.

Abdominal Neoplasms↗
PubMed1987

Altered kinetics of etozolin and its active metabolite ozolinone in hepatitis and hepatic cirrhosis with ascites.

The single dose kinetics of (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin) and its active metabolite ozolinone were determined in 6 healthy volunteers, in 12 patients with acute hepatitis and in 15 patients with hepatic cirrhosis with ascites. In hepatitis, the elimination half-life of etozolin was 4 times longer resulting in a 2 fold rise in the AUC. At the same time, plasma levels of ozolinone were lower and consequently the AUC of his metabolite was reduced. In cirrhosis, the plasma level time curves of etozolin and ozolinone differed significantly from the controls and also from those of the patients with acute hepatitis. For etozolin Cmax was reduced to about 1/2, the elimination half-life being increased by a factor of 5. This resulted in a 3 fold higher AUC. As for ozolinone the reduction of plasma levels was more pronounced--Cmax fell to 1/6 of the control value--so that in spite of a longer elimination half-life, the AUC fell to 1/2. Ascites concentrations of etozolin and ozolinone were almost identical to the plasma concentration. The results suggest that acute hepatitis and hepatic cirrhosis lead to a reduced formation of ozolinone. As a result, etozolin accumulates and plasma levels of oxolinone drop. Moreover, both substances enter the ascites to a significant degree. It is concluded that these changes in the kinetics of this lipophilic diuretic do not allow a reliable dosage regimen in patients with hepatic cirrhosis and ascites.

Acute Disease↗
PubMed1987

The information needs and fears of patients with inflammatory bowel disease.

A questionnaire containing a list of 36 questions and nine "fear factors" was sent to 139 patients with inflammatory bowel disease. Patients were asked to select the most and the least important questions and fear factors. Furthermore, the level of information and the source of information were recorded. 58% of the patients responded. The most important questions selected were possibilities of remission of the disease, and of developing cancer (47% and 43% of all answers respectively). Women judged questions regarding cancer, sex life, side effects of diagnostic techniques or drugs to be important more often than men, who were more interested in the cause, symptoms and natural history of the disease. Cancer was the fear factor selected most often (52%), being more important to patients with ulcerative colitis than to those with Crohn's disease, who in turn were more afraid of surgery than those with ulcerative colitis. 77% of the patients felt they had little or too little information. 87% received information from their physicians, 75% wanted to continue doing so. 62% wanted additional information from booklets, 18% from self-help groups. Thus, much information is lacking and many unjustified fears exist in patients with inflammatory bowel disease. This could probably be improved by providing more and better information by improved personal communication, and additionally from booklets or self-help groups.

Adult↗
PubMed1986

Clearance of acute-phase plasma proteins with no, high-mannose-, hybrid-, or complex type oligosaccharide side chains by the isolated perfused rat liver.

The clearance of the rat acute-phase proteins alpha 2-macroglobulin, alpha 1-proteinase inhibitor and alpha 1-acid glycoprotein with no, high-mannose, hybrid or complex type oligosaccharide side chains was determined in the isolated perfused rat liver. The differently glycosylated forms of the three proteins were obtained from rat hepatocyte primary cultures treated with different inhibitors of glycosylation. The complex type forms of the three proteins were essentially not cleared by the liver during 2 h of perfusion. Unglycosylated alpha 2-macroglobulin and alpha 1-acid glycoprotein decreased in the perfusate by about 50% after 2 h; unglycosylated alpha 1-proteinase inhibitor was not taken up by the liver. The high-mannose type forms of the three proteins were nearly totally cleared. After 2 h of perfusion 10%, 45% and 30% of the hybrid type forms of alpha 2-macroglobulin, alpha 1-proteinase inhibitor and alpha 1-acid glycoprotein, respectively, were cleared. The clearance rates of high-mannose and of hybrid type glycoproteins could be reduced to the rates of complex type glycoproteins by the addition of mannan to the perfusate. It is concluded that complex type glycosylation prevents the uptake of plasma glycoproteins by the liver.

1-Deoxynojirimycin↗
PubMed1986

[Drug therapy of chronic inflammatory intestinal diseases--current status of 5-aminosalicylic acid].

Assessment of the nature, location and extent of the disease, disease activity and the intestinal and extraintestinal complications and manifestations is an essential prerequisite in the treatment of inflammatory bowel disease. Corticosteroids, sulfasalazine (SASP) and rectal administration of 5-aminosalicylic acid (5-ASA) are effective in the treatment of ulcerative colitis. Oral 5-ASA in the form of a slow-release preparation is probably also effective. Rectal SASP or 5-ASA in addition to corticosteroids is indicated in distal colitis. In severe pancolitis oral or intravenous corticosteroids are required, whilst in less severe forms SASP or 5-ASA can be used. However, the safety of 5-ASA over longer treatment periods has yet to be verified. Surgery is indicated in colitis refractory to maximal treatment over several months. Apart from parenteral or enteral nutrition, treatment with prednisolone is effective in acute exacerbations of Crohn's disease. SASP is possibly effective in colonic disease. The role of 5-ASA has yet to be defined. A prednisolone-induced remission can be maintained by means of low doses of prednisolone. SASP is probably not effective, whilst with 5-ASA conclusive data are missing. Metronidazole and azathioprin are considered to be reserve drugs and can be used in the treatment of fistulae or in order to cut down the dosage of prednisolone during remission. Substitution with vitamins and trace elements is necessary in a large number of patients with Crohn's disease.

Adrenal Cortex Hormones↗
PubMed1986

Liver carbonic anhydrase and urea synthesis. The effect of diuretics.

In isolated perfused rat liver, urea synthesis is rapid and reversibly inhibited not only by the well-known carbonic anhydrase inhibitors acetazolamide, methazolamide and ethoxzolamide, but also by diuretics, like xipamide, mefruside, chlortalidone, and chlorothiazide. Furosemide was without effect. Similar to findings with isolated perfused rat liver, acetazolamide inhibits urea synthesis from ammonium ions in normal and cirrhotic human liver slices. Inhibition of urea synthesis by xipamide and acetazolamide is accompanied by a 70% decrease of the cellular citrulline content and the tissue levels of 2-oxoglutarate and citrate, suggesting a block of urea synthesis at a step prior to citrulline formation. At a constant extracellular pH (7.4), inhibition of urea synthesis by xipamide, mefruside and acetazolamide was overcome by increasing the extracellular concentrations of HCO3- and CO2 to above twice the normal values. This shows that inhibition of urea synthesis by these diuretics is not due to an unspecific inhibition of one of the urea cycle enzymes but is due to an inhibition of mitochondrial carbonic anhydrase and therefore due to an impaired HCO3- provision for mitochondrial carbamoylphosphate synthesis. It is concluded that the activity of mitochondrial carbonic anhydrase is required for urea synthesis also in human liver and that several diuretics impair urea synthesis by inhibition of mitochondrial carbonic anhydrase. The pathophysiological significance of these data is discussed with respect to the development of diuretics-induced hyperammonemia and alkalosis in liver disease.

Acetazolamide↗
PubMed1986

alpha-Amanitin uptake into hepatocytes. Identification of hepatic membrane transport systems used by amatoxins.

Hepatic transport studies with amatoxins, toxic bicyclic octapeptides from poisonous mushrooms of the genus Amanita were performed, using [(6'-O,1'-N-di[3H]methyl)trp4]-alpha-amanitin and [(6'-O,1'-N-di-methyl)trp4]-[4-[3H]desmethyl)hyi3]-gamma-ama nitin. Uptake into hepatocytes from rat liver was inhibited by taurocholate and antamanide. Photoaffinity labeling studies with isolated hepatocytes and basolateral plasma membranes, using the sodium salt of (7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-[3 beta-3H]cholan-24-oyl)-2- aminoethanesulfonic acid demonstrated that the presence of alpha-amanitin decreased the labeling of the two sinusoidal bile salt-binding membrane polypeptides with the apparent molecular weights of 54,000 and 48,000. In basolateral plasma membrane vesicles amanitin uptake was temperature-dependent and could be stimulated 1.5 to 2-fold by an out to in Na+ gradient as compared to a K+ gradient or sucrose and 2 to 2.5-fold as compared to amanitin equilibration (overshoot). Kinetic studies proved saturability of amanitin uptake in the presence and absence of a Na+ gradient. Membrane transport could be inhibited by taurocholate, antamanide, phalloidin, prednisolone, and silybin, but not by penicillin G or thioctic acid. Hepatic uptake of amatoxins is mediated by the sinusoidal bile salt-transport systems which are also involved in the uptake of antamanide and phalloidin. This supports the concept of a multispecificity of hepatic transport systems for a wide variety of amphipathic molecules.

Affinity Labels↗
PubMed1986

[Tryptophan metabolism in liver diseases: a pharmacokinetic and enzymatic study].

Tryptophan is considered to be one of the agents involved in the pathogenesis of hepatic encephalopathy. In our study, we evaluated tryptophan metabolism in liver disease. A bolus of 1.5 g of L-tryptophan was administered intravenously to 14 patients with noncirrhotic liver disease, 40 patients with liver cirrhosis, and 8 healthy volunteers. As pharmacokinetic parameters, the half life, clearance, and volume of distribution of free and total tryptophan were determined using a biexponential formula. In addition, the activity of liver tryptophan pyrrolase, the key enzyme of tryptophan metabolism, was measured in liver biopsy specimens of 15 patients with noncirrhotic liver disease, 8 patients with cirrhosis of the liver, and 4 patients with histologically normal livers. Healthy subjects and patients with noncirrhotic liver disease both showed similar results in measured and calculated data. In contrast, patients with cirrhosis revealed significant alterations of the pharmacokinetic parameters of free and total tryptophan: the half-life was increased by 195% and 176%, the clearance was decreased by 73% and 34%, respectively, and the activity of tryptophan pyrrolase was decreased by 22%. The tryptophan transfer in cirrhosis amounted to only 0.75 +/- 0.03 g per 24 h compared with 2.6 +/- 0.34 g per 24 h in healthy individuals. The findings demonstrate that patients with cirrhosis show a marked reduction in their ability to metabolize tryptophan. This should be taken into account in the oral and parenteral nutrition of those patients.

Adult↗
PubMed1986

[Clinical significance of sonographically detected splenomegaly].

In 502 patients, length, thickness and width of the spleen as well its location with respect to the ipsilateral kidney were determined by means of ultrasonography, and a relationship was established with the incidence of diseases accompanied by enlargement of the spleen. A significant correlation to the incidence of such diseases was found only with respect to spleen thickness. The probability of a corresponding disease was 80% for a spleen thickness of 5 cm, 90% for 6 cm and 100% for more than 7 cm. A comparison between palpation and ultrasonography supported the fact that enlargement of the spleen can, in many cases, not be ascertained by palpation, but that palpation findings are indeed positive in splenic enlargement of minor degree. The most suitable parameter for ultrasonographic detection of splenomegaly is thus spleen thickness, for which a limit value of 5 cm should be assumed. If the spleen is found to exceed this value, further examinations are indicated to clarify the underlying disease.

Humans↗
PubMed1986

[Unexpected findings during abdominal sonography. Their incidence and clinical significance].

19% of 1490 abdominal sonograms from 1192 patients led to findings which were not related to the original purpose of the sonogram or to the actual disease, and of which neither the treating physician nor the patient were aware. The most frequent findings were those in liver, kidneys and gallbladder. The majority of ultrasonographically detected lesions were benign; tumour diseases were suspected only in 26 cases. The incidence of such findings increased with the patients' age. The positive, predictive value of the findings was around 90%. In 20% of the patients with unexpected findings, further diagnostic measures were taken; therapeutic consequences were recorded in only twelve cases. Further measures were recommended in 20% of the patients, a majority of which had pancreatic and vascular abnormalities. Because such findings may considerably facilitate the diagnosis of subsequent complaints, all accessible organs should be examined during abdominal ultrasonography.

Abdomen↗
PubMed1986

The effect of urea synthesis on extracellular pH in isolated perfused rat liver.

In a non-recirculating system of isolated liver perfusion, stimulation of urea synthesis by NH4Cl is followed by a decrease of effluent pH by up to 0.2 pH unit. This effect is not observed when urea synthesis is inhibited by amino-oxyacetate or norvaline. When the urea formed by the liver is immediately hydrolysed with urease before the effluent perfusate reaches the pH electrode, the urea-synthesis-induced acidification is no longer observed. This indicates that accompanying alterations in hepatic metabolism after stimulation of urea synthesis, such as increased energy provision and consumption, are not responsible for the extracellular acidification, but that the effect is due to the formation of urea itself. The acidification of the extracellular space after stimulation of urea synthesis by NH4Cl is quantitatively explained by the consumption of 2 mol of HCO3-/mol of urea formed: 1 mol being incorporated into urea, the other being protonated to yield CO2 and H2O. The data match the theoretically predicted HCO3- consumption during ureogenesis and underline the role of hepatic urea synthesis for disposal of HCO3- by converting it into the excretable products CO2 and urea.

Ammonium Chloride↗
PubMed1986

Different oligosaccharide processing of the membrane-integrated and the secretory form of gp 80 in rat liver.

Rat liver synthesizes a glycoprotein with Mr of 80.000 (gp 80) which is partly inserted into the plasma membrane and partly secreted into the serum. The membrane-integrated and the secretory form of this glycoprotein have an identical peptide pattern, but different N-linked glycans. Whereas gp 80 from the serum is glycosylated with complex-type oligosaccharides, gp 80 from the plasma membrane has high mannose glycans. Phase separation with Triton X-114 showed that membrane-integrated gp 80 contains hydrophobic portions, whereas secretory gp 80 has hydrophilic properties. Intracellular transport and oligosaccharide processing of gp 80 were studied in vivo in the endoplasmic reticulum, the Golgi apparatus and plasma membranes of rat liver and in serum using pulse-chase labeling with L-[35S]methionine and immunoprecipitation. Peak labeling of gp 80 was reached in the endoplasmic reticulum 10 min after the pulse, in the Golgi apparatus 20 min later, and in the plasma membrane after 2 h; in the serum the specific radioactivity was steadily increasing during the experiment. Gp 80 of the endoplasmic reticulum was completely sensitive to endo-beta-N-glucosaminidase H (endo H), but simultaneously occurred in the Golgi apparatus in an endo H-sensitive and endo H-resistant form. The endo H-sensitive form was transported to the plasma membrane, the endo H-resistant species secreted into the serum. Conversion from the endo H-sensitive to the endo H-resistant form was completed within 10 min after transfer of gp 80 to the Golgi apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Benign circumscribed lesions of the liver diagnosed by ultrasonically guided fine-needle biopsy.

Cytologic evaluation of aspirates obtained by ultrasonically guided puncture of circumscribed lesions leads to the diagnosis of a malignant lesion when tumor cells are detected. In the absence of tumor cells, it remains uncertain whether the focus had been biopsied correctly, since the histologic diagnosis of a benign focal lesion can only occasionally be made by means of cytologic smears. Cases are presented showing circumscribed lesions of the liver. With a cut-biopsy fine needle, small cylinders of tissue were obtained under ultrasonic guidance and examined after histologic preparation. In each case, a benign focal lesion could be diagnosed, proving that the observed lesion had been correctly biopsied.

Adult↗
PubMed1986

Renin, aldosterone and arginine vasopressin in patients with liver cirrhosis: the influence of ascites retransfusion.

Plasma renin activity (PRA), and concentrations of aldosterone (PAL) and arginine vasopressin (AVP) in plasma were determined in 15 patients with ascites due to cirrhosis. The concentrations in ascites were analyzed simultaneously. Six patients were studied during extracorporeal ascites retransfusion. All but one patient with ascites showed elevated PAL (642 +/- 255 pg ml-1) and PRA (43 +/- 26 ng ml-1 h-1); all had increased AVP (7.3 +/- 5.1 pg ml-1). A low ascites to plasma ratio was found for aldosterone (0.023 +/- 0.023), but not for AVP (0.71 +/- 0.82). Retransfusion resulted in a normalization of central venous pressure (CVP), urinary volume, sodium/potassium ratio in urine, PAL and PRA, but not of AVP, serum sodium concentration and urinary sodium excretion. PRA and PAL increased again after cessation of treatment, while urinary output, CVP and sodium/potassium ratio in urine decreased. The results support the 'underfilling' concept, but give evidence that, in addition, other factors must be involved in the impaired natriuresis in cirrhotic patients. They further support the concept of volume expansion and increased renal perfusion as reason for the therapeutic efficacy of ascites retransfusion. Previous diuretic treatment seems not to be of importance for altered hormone metabolism in liver cirrhosis. Storage in a third compartment may be a factor in the persistently elevated AVP levels.

Adult↗
PubMed1986

Ion transport in rat proximal colon in vivo.

Active Na+ absorption by the rat proximal colon in vivo is for the most part electrically silent. The rheogenic Na+ flux makes up only 8%. To elucidate the underlying transport pathways, the following experimental approaches were used: ion substitution experiments such as choline for Na+, cyclamate for Cl-, variation of luminal pH; administration of known inhibitors; and determination of changes in luminal CO2 tension and pH. The transcolonic ion fluxes as well as the electrical parameters potential difference, specific electrical resistance, and short-circuit current were monitored. Na+ transport was drastically reduced in the absence of luminal Cl-, and vice versa Cl- absorption was blocked at zero Na+. NaCl absorption was blocked by amiloride (10(-3) M) and 4-acetamido-4'-isothiocyanostilbene-2, 2'-disulfonic acid and was lowered by acetazolamide. Colonic NaCl absorption was not influenced by luminal furosemide. Na+ absorption increased with alkalinization of the luminal fluid. Tris instead of HCO-3 buffer at constant pH favored Cl- uptake. The results may easily be explained by the operation of a Na+-H+ antiport functionally coupled to a Cl(-)-HCO-3 antiport. These transport processes are supposed to be present in the columnar cells of the colonic epithelium. There is good evidence for the association of K+ secretion with rheogenic Cl- secretion by the crypt cells.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1986

The acute-phase induction of alpha 2-macroglobulin in rat hepatocyte primary cultures: action of a hepatocyte-stimulating factor, triiodothyronine and dexamethasone.

During inflammation a number of liver-derived plasma proteins increases in concentration. In the rat these so-called acute-phase proteins are mainly proteinase inhibitors, such as alpha 1-proteinase inhibitor, alpha 1-acute-phase globulin and alpha 2-macroglobulin. At present, the mechanisms responsible for the enhanced synthesis of acute-phase proteins are poorly understood. Therefore, we have studied the induction of alpha 2-macroglobulin synthesis in rat hepatocyte primary cultures. Adrenaline, triiodothyronine, estradiol and progesterone were tested for their ability to stimulate alpha 2-macroglobulin synthesis. Only triiodothyronine induced alpha 2-macroglobulin synthesis markedly. However, the presence of dexamethasone was a prerequisite for alpha 2-macroglobulin induction indicating a permissive action of glucocorticoids. Besides glucocorticoids and triiodothyronine a non-dialyzable factor (HSF) derived from rat Kupffer cells or human peripheral blood monocytes was found to be able to stimulate alpha 2-macroglobulin synthesis in hepatocytes. Equal amounts of HSF activity were found in conditioned media from lipopolysaccharide-stimulated and unstimulated rat Kupffer cells as well as in human monocytes. Since the supernatants of unstimulated rat Kupffer cells or human monocytes did not exhibit interleukin 1 activity, HSF activity distinct from interleukin 1 must exist. No HSF activity was found in media conditioned by rat Kupffer cells which had been treated with dexamethasone. Hepatocyte primary cultures were incubated with [35S]methionine-labeled proteins secreted by rat Kupffer cells. A 30 kDa polypeptide was found to be bound to or internalized by rat hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗