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Biomedical subjects

G Feldmann

Publications and source records attributed to G Feldmann.

At least 253 records · Page 14Linked to original sources
PubMed1980

Influence of colchicine and phalloidin on bile secretion and hepatic ultrastructure in the rat. Possible interaction between microtubules and microfilaments.

The studies were carried out to examine the role of microtubules and microfilaments on bile secretion in the rat in vivo. Phalloidin (which causes irreversible polymerization of actin into microfilaments), administered at the dose of 50 microgram/100 g body wt during 3 days, caused an increase in the microfilamentous network around bile canaliculi; it induced a significant decrease both in basal bile flow, and in bile flow stimulated by sodium taurocholate, the major bile acid in the rat. Colchicine (which inhibits the polymerization of tubulin into microtubules), 3 hr after an injection of 0.2 mg/100 g body wt, caused the almost complete disappearance of microtubules in the hepatocytes; it did not modify basal bile secretion, but did induce a significant decrease in taurocholate secretion and taurocholate-stimulated bile flow after a bile-acid load, as well as a delayed plasma disappearance of the bile acid. Lumicolchicine, which is known to have no effect on tubulin, had no effect on bile secretion. The combined administration of phalloidin and colchicine caused both the increase of the pericanalicular microfilamentous network and the disappearance of microtubules; it induced a decrease in basal bile flow that was more marked than that observed with phalloidin alone, suggesting that the effects of the two drugs were not simply additive, but synergic. Although a toxic effect of colchicine could not be totally excluded, the results are compatible with the hypothesis that microtubules as well as microfilaments play a role in the excretion of a bile-acid load.

Alanine Transaminase↗
PubMed1980

In vivo and in vitro effects of colchicine and vinblastine on the secretory process of antibody-producing cells.

The sensitivity of the secretory process of antibody-synthesizing cells to microtubule-binding drugs, colchicine and vinblastine sulfate, was studied. Rats were immunized by footpad injections of horseradish peroxidase, and the popliteal lymph nodes were removed at various times after injection. Both in vivo effects of colchicine and in vitro effects of colchicine and vinblastine were studied. Quantitative data were obtained with in vitro drug-treated cells by labeling with L-3H-leucine and by measuring the secreted and the cytoplasmic immunoglobulins. It was found that inhibition of immunoglobulin secretion was about 78% and 93% by colchicine and vinblastine, respectively. the results obtained with the latter drug were more difficult to interpret because it also inhibited the biosynthesis of total proteins, and particularly that of immunoglobulins. Immunocytochemical studies of the in vivo and in vitro drug-treated cells performed by light and electron microscopy showed that in antibody-containing cells the Golgi area was often occupied by dilated antibody-containing vesicles, probably derived from the Golgi apparatus. In a few of these cells it was observed that antibody-containing rough endoplasmic reticulum was markedly dilated. the above results demonstrate that both microtubule-binding agents, colchicine and vinblastine, are potent inhibitors of the secretory process of plasma cells and seem to indicate that a correlation may exist between ultrastructural changes and inhibition of secretion.

Animals↗
PubMed1980

Electron microscopy of fibrin Paris I.

Fibrinogen Paris I, a congenital fibrinogen abnormality, is characterized by delayed fibrin aggregation and poor clot retraction owing to the replacement of normal gamma-chains by mutant gamma-chains, which are termed gamma-Paris I. Available evidence indicates that the structural abnormality involves the amino acid sequence near the COOH-terminus of the mutant chain and probably includes the region containing the normal gamma-chain crosslinking site. Electron microscopy was carried out on Paris I fibrin. In place of the normally interwoven network of branching cross-striated fibers, negatively or positively contrasted Paris I fibrin was characterized by nonfibrous clumps of material connected by distince fibrous strands tending to be thinner and more irregular in width than normal fibrin. Most Paris I fibrin fibers tended to the aperiodic, although cross-striations were observed occasionally in negatively contrasted specimens and rarely in positively contrasted specimens. In addition, Paris I fibrin frequently showed relatively short, abruptly terminating fibers. The gross ultrastructural differences between normal and Paris I fibrin suggest that for fibrin assembly to take place normally, a region(s) in the fibrin molecule near to or possibly overlapping the COOH-terminal gamma-chain crosslinking site must be preserved or at least not sterically hindered.

Amino Acid Sequence↗
PubMed1979

Idiopathic portal hypertension (perisinusoidal fibrosis) after renal transplantation.

We report the cases of two renal transplant recipients suffering from idopathic portal hypertension, a condition characterised by increased portal venous pressure in the absence of both histological lesion of the liver and obstruction of the portal vein. In these two patients, perisnusoidal fibrosis, invisible by light microscopy, was demonstrated by electron microscopy; it is suggested that partial obstruction of hepatic sinusoids by perisinusoidal fibrosis could be the mechanism for increased portal venous pressure in all the patients with idiopathic portal hypertension. In these two patients, who received 6-mercaptopurine and azathioprine, perisinusoidal fibrosis might be the consequence of prolonged administration of these drugs.

Adult↗
PubMed1979

Gold salt-induced cholestasis.

The authors report the case of a patient with transient intrahepatic cholestasis following the administration of a soluble gold salt, sodium aurothiopropanol sulfonate. Other manifestations of intolerance to gold salts included exfoliative dermatitis and eosinophilia.

Aged↗
PubMed1979

Inhibition of hepatic drug-metabolizing enzymes by arachidonic acid.

1. The effects of arachidonic acid on hepatic drug-metabolizing enzymes was investigated in male ICR-Swiss mice. 2. A single administration of arachidonic acid, 100 mg/kg i.p., doubled the hexobarbital sleeping time. Arachidonic acid in vitro gave a type I binding spectrum with hepatic microsomes; it inhibited the metabolism of hexobarbital and of ethylmorphine, two type I binding drugs, but not that of aniline, a type II binding drug; the inhibition of hexobarbital metabolism by arachidonic acid was competitive. 3. Repeated administration of arachidonic acid up to a total dose of 1000 mg/kg i.p., either in the course of 5 hours, or in the course of 5 days, decreased microsomal cytochrome P-450 levels and NADPH-cytochrome c reductase activity. 4. It is concluded that the administration of arachidonic acid may impair drug metabolism in two ways, mainly, by competitively inhibiting the activity of drug-metabolizing enzymes, and secondarily, by decreasing the hepatic concentration of these enzymes.

Animals↗
PubMed1979

Perhexiline maleate-induced cirrhosis.

The authors report the cases of 2 patients who died from cirrhosis after receiving perhexiline maleate, a drug widely used in Europe for the treatment of angina pectoris. Perhexiline maleate had been ingested for 24 and 28 mo, respectively. Manifestations of cirrhosis included jaundice, hepatic encephalopathy, ascites, and portal hypertension. Associated manifestations of intolerance to perhexiline maleate included peripheral neuropathy in 1 patient and marked weight loss in both. Histologic lesions resembled those observed in patients with alcoholic liver disease. Ultrastructural lesions included numerous enlarged lysosomes containing myeloid figures. Histochemical stains demonstrated increased phospholipid content of the hepatocytes. These findings are consistent with the view that prolonged administration of perhexiline maleate may induce both histologic lesions resembling those of alcoholic liver disease and ultrastructural and histochemical lesions resembling those of phospholipidosis.

Aged↗
PubMed1978

Control of the acute phase response. Demonstration of C-reactive protein synthesis and secretion by hepatocytes during acute inflammation in the rabbit.

To determine the cell of origin of C-reactive protein (CRP) and to cast light on the mechanisms leading to the acute phase response, we used an immunoenzymatic technique to visualize this protein in livers from rabbits at intervals after intramuscular injection of turpentine. CRP was detected only in hepatocytes. 8 h after turpentine injection, CRP was demonstrated in occasional periportal hepatocytes. With time, larger numbers of positive cells were detected successively in perilobular, midlobular, and centrilobular areas. On electron microscopy, CRP was detected in rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SER), and Golgi apparatus (GA). When colchicine was administered to inhibit cellular secretion of CRP, intensity of reaction and number of CRP-containing hepatocytes were substantially greater than without colchicine, but the sequence of intralobular distribution was similar. At peak serum response 38 h after turpentine injection, CRP could be demonstrated in most hepatocytes. Electron microscopic studies showed accumulation of CRP on membranes and lumina of RER, SER, GA, and in cytoplasmic vacuoles. These findings indicate that CRP is produced by progressively increasing numbers of hepatocytes after inflammatory stimulus and suggest that a mediator, acting initially in portal zones, is responsible for recruitment of cells to CRP production.

Animals↗
PubMed1978

[Pulmonary emphysema and hepatic involvement by alpha-1 antitrypsin deficiency in two adults with a PiZ phenotype (author's transl)].

Two unreleated adult males were found to be suffering from an association of pan-lobular severe emphysema and hepatomegally of unknown origin which led to the discovery of a marked deficit in alpha-1 antitrypsin (A1-AT) in relation to a PiZ phenotype. Liver biopsy revealed cirrhosis with portal fibrosis in one case and in both cases fatty infiltration with the accumulation of a glycoprotein antigenically identical to A1-AT. Electron microscopy showed this protein to be situated within the dilated lumina of the endoplasmic reticulum of the hepatocytes. A1-AT deficiency is usually associated with pulmonary involvement only in the adult and liver involvement only in the child. The association of the two remains rare--hence the interest of the two cases reported.

Adult↗
PubMed1978

Hodgkin's disease: ultrastructural localization of intra-cytoplasmic immunoglobulins within malignant cells.

An immunoperoxidase technique has been applied to the detection of intracellular immunoglobulins at the light and ultrastructural levels in three untreated cases of Hodgkin's disease. The results are compared with those obtained in three treated cases. In both groups, 20-90% of malignant cells had intra-cytoplasmic immunoglobulins. There was no correlation between the percentage of immunoglobulin-containing cells and the histological type or the stage of the disease. At the ultrastructural level, immunoglobulins were constantly localized on cytoplasmic ribosomes, the later being either free in the cytoplasm or bound to the endoplasmic reticulum and to the external envelope of the perinuclear space. In addition, a very few malignant cells exhibited immunoglobulins within their perinuclear space and their endoplasmic reticulum. These results demonstrate that immunoglobulins in Hodgkin's malignant cells are present on the cellular sites of protein synthesis. They appear to be retained in their cytoplasm, and to be secreted only very occasionally. The significance of these findings as to the cellular origin of malignant cells in Hodgkin's disease is briefly discussed.

Adolescent↗
PubMed1978

Location of adult and fetal aldolases A, B, and C by immunoperoxidase technique in LF fast-growing rat hepatomas.

The resurgence of aldolase isozymes in cancerous tissues is a well-known but poorly understood phenomenon. This resurgence poses the problem of whether or not adult and fetal aldolase isozymes are produced by the same cells. For clarification of this question, the immunoperoxidase technique was used to locate aldolases A, B, and C in one type of fast-growing hepatoma, the LF hepatoma and, by comparison, in normal adult liver. Under optical microscopy, aldolases A and C were located in the cytoplasm of almost all of the cancerous cells. An isozyme antigenically identical with aldolase B was also demonstrated to be present in almost all of the cells, but the reaction indicating the presence of this isozyme was weaker. In normal adult liver, only aldolases A and B were demonstrated to be present in almost all the hepatocytes. Under electron microscopy in LF hepatoma, the three isozymes were found to be present mainly in the cytoplasm. These facts suggest that the three types of aldolase are very probably present in the same cells at the same time, and they provide indirect arguments leading us to think that the resurgence of fetal aldolase isozymes in cancer is not the consequence of cellular selection but is due to a disturbance at the gene control level.

Animals↗
PubMed1978

Metabolic activation of trichloroethylene into a chemically reactive metabolite toxic to the liver.

The mechanism for trichloroethylene hepatotoxicity was investigated in male Sprague-Dawley rats. Phenobarbital pretreatment increased and CoCl2 pretreatment decreased trichloroethylene hepatotoxicity. After administration of 1(14)C]trichloroethylene, a radioactive material became irreversibly bound to hepatic proteins, while negligible amounts were bound to muscle proteins. When 1(14)C]trichloroethylene was incubated under air with hepatic microsomes and a NADPH-generating system, a radioactive material became irreversibly bound to microsomal proteins; binding was negligible when the NADPH-generating system was omitted; binding was inhibited by carbon monoxide and by piperonyl butoxide; the amount of bound material was greater with microsomes from phenobarbital-pretreated rats and lower with microsomes from CoCl2-pretreated rats than with microsomes from nonpretreated rats. Trichloroethylene administration decreased hepatic glutathione in normal rats but not in piperonyl butoxide-pretreated rats; in vitro, glutathione decreased the amount of trichloroethylene material that bound to microsomal proteins. The reported results are consistent with the view that 1) trichloroethylene is metabolized by cytochrome P-450 into a chemically reactive metabolite which reacts with, and binds to, either proteins or glutathione, 2) binding to proteins produces liver lesions and 3) binding to glutathione decreases the amount of reactive metabolite available for binding to proteins.

Animals↗
PubMed1978

[Acrodermatitis enteropathica. Anatomo-clinical study of 2 familial cases treated with zinc sulfate].

Two familial cases of acrodermatitis enteropathica began at the time of weaning, with characteristic dermatologic lesions and digestive signs, resulting in lack of weight gain: at 13 months of age growth future was evident in the elder child. The anatomic lesions were those of an exophagitis and, in the duodenal mucosa, a dilation of the capillaries of the chorion in the absence of villous atrophy. The ultrastructural study showed inclusions in Paneth's cells, and changes in keratin cells, with intra-cytoplasmic vacuoles and abnormal melanin pigment in the skin. The administration of zinc sulphate induced a rapid recovery of cutaneous lesions and resumption of growth. The interruption of treatment resulted twice in a quite immediate relapse of cutaneous signs in the first patient, which was rapidly reversible with the reintroduction of zinc sulphate.

Acrodermatitis↗
PubMed1978

Phalloidin-induced cholestasis in the rat: relation to changes in microfilaments.

The influence of phalloidin, an agent that causes irreversible polymerisation of actin into microfilaments, on bile secretion and hepatocyte ultrastructure was examined in rats. Phalloidin was given intraperitoneally at the dose of 50 microgram per 100 g of body weight per day for 1, 3, or 7 days. The following was observed. (1) Bile flow decreased, as compared to controls, by 19% after 1 day, 34% after 3 days, and 55% after 7 days. Bile acid secretion was also decreased. (2) Electron microscopic examination of the hepatocyte in treated animals revealed an increased thickness of the pericanalicular microfilamentous network and a dilatation of bile canaliculi. Stereological examination revealed an increase in the relative volume of the microfilamentous network (per unit of hepatocyte cytoplasm) of 2.55% after 1 day, 4.06% ater 3 days, and 6.16% after 7 days. (3) [14C]Erythritol biliary clearance, measured after 7 days, decreased in parallel to bile flow, suggesting that the decrease in bile flow was of canalicular origin. [14C]Sucrose biliary clearance increased in treated animals, suggesting an increased permeability of the biliary system to sucrose. There was a predominant decrease in the bile acid independent bile flow. These data provide circumstantial evidence for the hypothesis that microfilament dysfunction can produce cholestasis.

Animals↗