Alterations of D-galactose metabolism in Morris hepatomas.

Studies on Morris hepatomas demonstrate that the specific activity of the enzymes of the Leloir pathway are subject to a variation in tumor tissue. The key enzyme of the galactose pathway, uridine diphosphogalactose 4'-epimerase, is elevated 5- to 9-fold in the rapidly growing and poorly differentiated Tumors 3924A and 7777; in line 9618A2, an even 28-fold increase was found. The observed correlation between enzyme activity, growth rate, and degree of differentiation of the hepatoma suggests that the differences are not coincidental variations. Conversely, the activity of uridine diphosphoglucose: galactose-1-phosphate uridyltransferase was diminished by 40 to 70% as compared to host liver, and the level of galactokinase showed only minor changes. The uptake of galactose and galactosamine by the hepatoma is heavily impaired, whereas the transport of other hexoses and amino sugars (2-deoxyglucose, L-fucose, N-acetylglucosamine, N-acetylmannosamine) is hardly affected. It appears that part of the carrier-mediated diffusion for hexoses is altered without a decisive impact on the whole system. Moreover, autoradiographic analysis of [14C]galactose-labeled tumor plasma membranes revealed a shift of the incorporation pattern from high- to lower-molecular-weight galactopolypeptides. Our results indicate that specific alterations of the D-galactose metabolism are a characteristic feature of Morris hepatomas.

Effect on vitamin A on the development of galactosamine-induced hepatitis in rats.

In order to elucidate the role of lysosomes in experimental hepatitis caused by D-galactosamine in rats the activities of cathepsin A and D and acid carboxypeptidase were measured. Enzyme activities were assayed in liver homogenate, lysosomal supernatant fraction and lysosomal sediment fraction. Lysosomal enriched fractions were prepared according to De Duve. Vitamin A in high doses aggravates the morphological alterations observed in galactosamine treated rats. At the same time the labilization of lysosomes increases substantially. This effect was induced by doses of retinyl-palmitate that normally caused only an activation of Kupffer cells and no significant liberation of lysosomal peptidehydrolases. The activities of cathepsin A and D increased 2-fold in liver homogenate after combined treatment with galactosamine and vitamin A, whereas the activity of acid carboxypeptidase decreased markedly.

Impedance cardiography the reproducibility of stroke volume measurements under conditions of mass examination.

The stroke volume at rest of 81 test subjects with no evident cardiac or circulatory dysfunction was determined by impedance cardiography and the measurements were repeated after 11 weeks. In order to attain comparable and reproducible conditions, 44 test subjects were chosen who showed heart rates at rest not higher than 83 beats per min, and whose changes in heart rate between the two tests were not greater than 11 beats per min. The stroke volumes determined by impedance cardiography are greater than those measured with the invasive methods reported by other authors. If the electrodes are removed between the tests sufficient reproducibility is not obtained. It is concluded that determinations of stroke volume by impedance cardiography as described in the literature are only suitable for detecting directional changes when the electrodes are left in place. It is impossible to obtain comparable data with electrodes once removed and replaced for the second measurement. Impedance cardiography is based on theoretical assumptions which do not permit estimation of errors affecting the measurement.

Different half-lives of the carbohydrate and protein moieties of a 110,000-dalton glycoprotein isolated from plasma membranes of rat liver.

By using a four-step procedure (i, solubilization with Triton X-100; ii, affinity chromatography on concanavalin A-Sepharose; iii, affinity chromatography on wheat germ lectin-Sepharose; iv, preparative sodium dodecyl sulfate gel electrophoresis) a glycoprotein was isolated from rat liver plasma membrane. The molecular weight is 110,000 and the isoelectric point is 5.8. It contains L-fucose, N-acetylneuraminic acid, D-galactose, D-mannose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, and considerable quantities of aspartate, threonine, serine, and leucine. In pulse-chase experiments the half-lives of methionine and arginine, representing the half-life of the protein, were determined as 70 hr and 78 hr, respectively. The half-lives of the terminal carbohydrates L-fucose and N-acetylneuraminic acid were 12.5 and 33 hr, respectively. The galactose half-life was 20 hr. From this it is concluded that terminal sugars turn over several times in the life-span of this protein molecule. This process may be operative during membrane recycling mechanisms.

[Functional and morphologic findings following chronic vitamin A deficiency in young rats]. / Funktionelle und morphologische Befunde nach einem chronischem Vitamin-A-Mangel bei jungen Ratten.

Pregnant rats were fed a vitamin A-depleted diet. After weaning, 40 litters (10 controls, 30 experimental) were divided into eight groups, four female and four male. All groups were given the same diet. The control groups (male and female) received 100 IU vitamin A/day, the deficient groups only a maintenance dose of 1-2 IU vitamin A/day. One female and one male group were repleted with vitamin A after the 27th day of life and two further groups of both sexes were repleted after the 49th day of life. After the 23th day of life all litters were trained for the Rail Test and after the 27th day the time on the rotating bar was recorded. After the 15th week all the animals were anesthetized and decapitated and the cochleas prepared for histologic and electronmicroscopic examinations. The vitamin A-deficient animals displayed delayed development of the visual, auditory, vestibular and motor systems in both sexes. Early repletion with vitamin A after the 27th day of life normalized the motor and vestibular systems to normal in the experimental animals. Late repletion with vitamin A, after the 49th day, does not normalize function in the Rail Test. In histologic studies some of the experimental animals showed dysplasia of the bony and membranous labyrinths. Others had signs of degeneration of the organ of Corti and the spiral ganglion of the cochlea. In the electron-microscopic studies an accumulation of lysosomes in the sensory cells and supporting cells, and dystrophic neuronal fibers and ganglion cells were found in the spiral ganglions of the vitamin A-deficient groups and to a lesser extend also in the groups with late repletion.(ABSTRACT TRUNCATED AT 250 WORDS)

[Coincidence of Gaucher disease with primary hepatocellular carcinoma]. / Koinzidenz eines Morbus Gaucher mit primärem hepatozellulärem Karzinom.

Case report on a 48-year-old man with Gaucher's disease and a HBsAg-positive cirrhosis simultaneously. Postmortem examination revealed a hepatocellular carcinoma suggested by antecedent ultrasound examination. The coexistence of Gaucher's disease and hepatocellular carcinoma has not been described before. A possible relationship between Gaucher's disease and hepatocellular carcinoma is supposed due to Gaucher's disease and association to the hepatitis B infection.

[Changes in the esophageal wall following sclerotherapy of varices--roentgen morphology and therapy]. / Veränderungen der Osophaguswand nach Varizensklerosierung--Röntgenmorphologie und Therapie.

Endoscopic sclerotherapy of esophageal varices is a widely used procedure. It reduces the frequency of rebleeding and improves the survival of cirrhotics with portal hypertension. The intravariceal or paravariceal injection of sclerosing agents causes structural changes of the esophageal wall recognisable radiologically. Stricture is a late complication which occurs in about 10 percent. In residual dysphagia balloon dilatation is recommended.

[Liver calcifications in metastasizing vipoma]. / Leberverkalkungen bei metastasierendem Vipom.

A 53-year-old woman had suffered from watery diarrhoea and substitution-requiring hypokalaemia for 18 months. Ultrasonography and abdominal x-ray revealed multiple calcifications in the liver. Retrograde cholangiopancreaticography, performed because an endocrine-secreting pancreatic tumour was suspected, demonstrated occlusion of the major pancreatic duct and calcification in the body of the pancreas. Gastrointestinal hormone levels were elevated (vasoactive intestinal polypeptide 950 pg/ml, pancreatic polypeptide 1000 pmol/l and neurotensin 86 pmol/l) in the blood, and immunohistochemical results on cells of an adenocarcinoma obtained by needle biopsy confirmed a metastasizing VIPoma. Administration of the somatostatin analogue SMS 201-995 achieved marked improvement.

Effect of phenytoin, carbamazepine, and valproic acid on caffeine metabolism.

Three groups of non-smoking epileptic patients without liver disease receiving antiepileptic monotherapy have been compared with 10 healthy non-smoking volunteers. Group 1 received phenytoin (n = 10), Group 2 carbamazepine (n = 10) and Group 3 valproic acid (n = 6). Cytochrome P-450 activity was monitored by measuring urinary 6-beta-hydroxycortisol output and systemic antipyrine clearance. Both, 6-beta-hydroxycortisol output and antipyrine clearance were significantly enhanced in patients on phenytoin and carbamazepine, but not in those on valproic acid. On the other hand, phenytoin alone increased the clearance of caffeine from 1.5 (controls) to 3.6 ml.min-1.kg-1, and reduced its half life from 4.8 to 2.4 h. Carbamazepine and valproic acid had no effect on caffeine metabolism. The results are in keeping with the well known heterogeneity of the hepatic monooxygenase system, as phenytoin and carbamazepine induce different panels of cytochrome P-450 isoenzymes. Phenytoin treatment may impair the validity of the caffeine liver function test.

[Zinc and vitamin A deficiency in gastrointestinal diseases]. / Zink- und Vitamin A-Mangel bei gastroenterologischen Erkrankungen.

It has been established rather surely that patients with chronic liver disease, Crohn's disease, chronic pancreatis and celiac disease are deficient in zinc and vitamin A. A large number of clinical symptoms can be caused by these deficiencies, due to the fact that these compounds have numerous functions. Zinc deficiency in liver cirrhosis is probably caused by portosystemic shunting, whereas in Crohn's disease abnormalities of protein metabolism are suggested as etiologic factor. Vitamin A deficiency can be considered as a consequence of disturbed zinc metabolism. Some studies in appropriate patients receiving substitution therapy with zinc and/or vitamin A had positive results. However, the necessity of substitution in the diseases mentioned has not yet been conclusively demonstrated.

N-glycosylation of membrane glycoproteins in retinol-deficient rat liver.

The effect of vitamin A deficiency on N-linked oligosaccharides of membrane glycoproteins was studied in rat liver in order to evaluate the suggested role of retinol in protein N-glycosylation. First, oligosaccharides of newly synthesized glycoproteins from rough endoplasmic reticulum of vitamin A deficient liver were compared with that of pair-fed controls. Oligosaccharides were metabolically labelled with D-[2-3H]mannose, released from the glycoproteins with endoglycosidase H, purified by reversed phase HPLC and ion exchange chromatography, and were reduced with sodium borohydride. HPLC fractionation of the oligosaccharide alditols showed that the glycoproteins carried mainly four oligosaccharide species, Glc1Man9GlcNAc2, Man9GlcNAc2, Man8GlcNAc2 and Man7GlcNAc2, in identical relative amounts in the vitamin A deficient and the control tissue. In particular, no increase in the proportion of short chain oligosaccharides was noted in vitamin A deficient liver. Second, the number of N-linked oligosaccharides was estimated in dipeptidylpeptidase IV (DPP IV), a major glycoprotein constituent of the hepatic plasma membrane, comparing the newly synthesized glycoprotein from rough endoplasmic reticulum and the mature form of DPP IV from the plasma membrane. No evidence was obtained that retinol deficiency caused incomplete glycosylation of this membrane glycoprotein. From these data, the suggested role of retinol as a cofactor involved in the synthesis of N-linked oligosaccharides of glycoproteins must be questioned.