Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homozygous inheritance of the Z-type mutant form of the alpha 1-antitrypsin (alpha 1AT) gene results in the most common form of alpha 1AT deficiency, a human hereditary disease associated with a high risk for the development of emphysema and an increased incidence of neonatal hepatitis. The alpha 1AT-synthesizing cells of individuals with the Z gene have normal alpha 1AT messenger RNA levels, but alpha 1AT secretion is markedly reduced secondary to accumulation of newly synthesized alpha 1AT in the rough endoplasmic reticulum. Crystallographic analysis of alpha 1AT predicts that in normal alpha 1AT, a negatively charged Glu342 is adjacent to positively charged Lys290. Thus the Glu342----Lys342 Z mutation caused the loss of a normal salt bridge, resulting in the intracellular aggregation of the Z molecule. The prediction was made that a second mutation in the alpha 1AT genet that changed the positively charged Lys290 to a negatively charged Glu290 would correct the secretion defect. When the second mutation was added to the Z-type complementary DNA, the resulting gene directed the synthesis and secretion of amounts of alpha 1AT similar to that directed by the normal alpha 1AT complementary DNA in an in vitro eukaryotic expression system. This suggests the possibility that a human hereditary disease can be corrected by inserting an additional mutation in the same gene.
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PMID:Repair of the secretion defect in the Z form of alpha 1-antitrypsin by addition of a second mutation. 290 2

The infection of murine fibroblasts of the sac- line with a coronavirus, mouse hepatitis virus strain A59 (MHV-A59), results in a novel modification to some cisternae of the rough endoplasmic reticulum (RER). From 8 hours post infection (h.p.i.) we see in thin sections pairs of cisternae closely, stably and uniformly aligned. Serial sectioning shows that the regions of pairing or lamination extend for many thousands of nm in two dimensions, with the spacing between the juxtaposed membranes remaining very uniform at about 18 nm. These structures appear coincident with the onset of accumulation of the viral glycoprotein E1 in the RER membrane but 2 hours after the viral glycoprotein E2 can first be detected there. Ribosomes are excluded from the paired cisternal surfaces, while budding of progeny virions has never been seen at the cisternal membranes facing the cytosol, although ribosomes bind there. The lumina of paired cixternae are usually devoid of virions which, however, accumulate in areas where the paired cisternae diverge. Electron immunocytochemistry shows that both E1 and E2 glycoproteins are abundant in the paired cisternae. Following labelling for the E1 glycoprotein we see a periodic fine structure, rows of "beads" with a centre to centre spacing of about 7.5 nm, in the region between the paired membranes. In oblique sections of this region in cells fixed as if for the immunoperoxidase labelling, but omitting all its steps we see parallel rows of "beads" separated by about 7 nm. We suggest that the membrane spanning viral glycoprotein E1 together with viral nucleocapsids may be involved in laminating cisternae of the RER.
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PMID:Laminated cisternae of the rough endoplasmic reticulum induced by coronavirus MHV-A59 infection. 298 95

AtT20 cells, a line of murine pituitary tumour cells that secrete adrenocorticotropic hormone (ACTH), have been infected with the coronavirus mouse hepatitis virus strain A59 (MHV-A59). Between 5% and 10% of AtT20 cells are susceptible to the infection. Unlike infections of fibroblastic sac- and 17Cl 1 cells, the infection of AtT20 cells does not lead to cell fusion, despite the production of the fusogenic E2 viral spike glycoprotein. Within infected AtT20 cells the second viral envelope glycoprotein, E1, is located in a perinuclear region; at least until very late in the infection it fails to accumulate to detectable levels in the rough endoplasmic reticulum (RER). By contrast to infection of sac- and 17Cl 1 cells, where the RER is a major site of assembly of progeny virions, in AtT20 cells budding of progeny virions is restricted to the Golgi cisternae, which eventually vesiculate, and peri-Golgi smooth membraned vesicles. Apparently, therefore, the intracellular compartments into which wild-type MHV-A59 buds are determined not by the virus but by the host cells. MHV-A59 infected cultures of AtT20 cells can be serially passaged without loss of the infection or increase in the proportion of infected cells; they become persistently infected carrier cultures. The progeny virus from serially passaged, infected AtT20 cells is apparently wild-type. It infects sac- cells and induces them to form syncitia. Within the sac- syncitia the viral E1 glycoprotein accumulates in the RER and many virions assemble there.
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PMID:Infection of AtT20 murine pituitary tumour cells by mouse hepatitis virus strain A59: virus budding is restricted to the Golgi region. 299 76

Cloned cDNA encoding the membrane glycoprotein E1 of the coronavirus mouse hepatitis virus strain A59 was expressed transiently in a monkey fibroblast cell line (COS) by using a simian virus 40-based vector. As determined by indirect immunofluorescence microscopy, the E1 protein accumulated intracellularly in a perinuclear region coincident with a Golgi marker. The same three species of E1 that occur in virus-infected cells were also found in transfected cells. These are one unglycosylated form and two apparently O-glycosylated forms that could be labeled in a tunicamycin-resistant fashion with [3H]glucosamine. Because O glycosylation occurs posttranslationally in the Golgi apparatus, we could show, by monitoring the rate of acquisition of oligosaccharides, that the transport of E1 from the rough endoplasmic reticulum to the Golgi apparatus had a half time of between 15 and 30 min.
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PMID:Coronavirus E1 glycoprotein expressed from cloned cDNA localizes in the Golgi region. 303 31

Anti-endoplasmic reticulum antibody positive autoimmune hepatitis in children is characterized by the recognition of a single 50,000 MW protein of the endoplasmic reticulum in liver microsomal fractions by their sera. We have developed an enzyme-linked immunosorbent assay technique with rat liver microsomal preparations as the antigen to be used for detection of this disease. Titers obtained may be useful in following the course of the disease and as an aid in determining when therapy can be discontinued. The technique is rapid, sensitive, reproducible, and simple to perform and is easier to manipulate than immunofluorescence or radioimmunoassay techniques.
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PMID:Detection of anti-endoplasmic reticulum antibody-positive autoimmune hepatitis in children, using an ELISA technique. 305 18

Ultrastructural changes were observed in 23 consecutive patients who died from fulminant hepatic failure due to hepatitis B virus (4 cases), sporadic non-A, non-B (7), or paracetamol (acetaminophen) overdose (12) and in 3 patients with subacute hepatic necrosis of unknown cause. The findings are described in detail in 12 of these patients. Fatal fulminant hepatitis was characterised by massive confluent necrosis accompanied by collapse of reticulin framework and sudden drop-out of liver cells. No aetiological distinction could be made between different viral causes of fulminant hepatitis on the basis of ultrastructural pathology. Parenchymal changes in viral cases varied from reversible non-specific necrosis to irreversible changes where fragmentation of endoplasmic reticulum, mitochondria and nuclei had occurred. Differences in ultrastructural pathology between non-viral (paracetamol overdose-induced) and viral fulminant hepatitis were apparent. Modification of endoplasmic reticulum with enlarged attached polyribosomes, breakdown of plasma membrane, accumulation of cytoplasmic amorphous material and karyorrhexis and karyolysis of nuclei were the most prominent features in non-viral cases.
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PMID:Fulminant hepatitis. An ultrastructural study. 308 70

In this study the morphological changes in the livers of marmosets inoculated with stool extracts from epidemic non-A, non-B hepatitis patients in India were examined. The histologic changes of epidemic non-A, non-B hepatitis in marmosets consisted mainly of round cell infiltration in the portal tracts, spotty liver cell necrosis, sinusoidal lymphocyte infiltration, and Kupffer cell mobilization. By electron microscopy, liver cells from infected marmosets showed cisternal dilation of the endoplasmic reticulum, irregularly-shaped nucleus, and disorganization of the mitochondrial cristae. In some areas interaction of lymphocytes with hepatocytes was observed. Similar observations have been made in type B hepatitis infection, presumably due to liver cell damage mediated by immune mechanisms. The result of our study is also compatible with the interpretation that the liver cell damage in this experimental model may be mediated by immune mechanisms.
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PMID:Liver morphology in marmosets infected with epidemic non-A, non-B hepatitis in India. 309 79

Hepatitis B virus associated antigens and subsets of lymphocytes in liver tissue were studied using immune electron microscopy to clarify the immune mechanism of hepatocyte lysis in type B chronic hepatitis. Using conventional electron microscopy, infiltrating lymphocytes were observed in direct contact with hepatocytes in areas of piecemeal necrosis and focal necrosis; they showed various types of surface adherence with a contact gap of approximately 20 nm in width. The majority of the hepatocytes that were in contact with lymphocytes could be shown to contain HBsAg and/or HBcAg by immune electron microscopy: HBsAg was localized in the endoplasmic reticulum membranes, in tubular structures, and on the outer coat of Dane particles; HBcAg was observed in the nuclei and in the cytoplasmic matrix of hepatocytes. In some cases HBsAg was observed on the plasma membrane of hepatocyte in contact with lymphocytes. Immune electron microscopy using monoclonal antibodies to subsets of human T-lymphocytes revealed that the lymphocytes in areas of piecemeal necrosis and focal necrosis were predominantly CD 5 or CD 8 positive. In contrast, CD 4 positive cells were infrequently observed in necro-inflammatory regions and Leu 7 positive cells were randomly scattered in the sinusoids away from areas of hepatocyte necrosis. These data suggest that HBsAg is at least one of the target antigens expressed on the hepatocyte membrane possibly enabling cytolytic interaction by cytotoxic T cells in chronic type B hepatitis.
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PMID:Interaction of lymphocytes with hepatocytes containing hepatitis B antigen: ultrastructural demonstration of target antigen and T-cell subsets by the peroxidase antibody technique. 311 64

Changes in uridine-diphosphate glucuronyl transferase activity (UDP-GT) in liver homogenates of hamsters treated with different doses of isoniazid (INH), rifampicin (RMP), para-aminosalicylic acid (PAS) and hydrocortisone for several periods of time were studied and expressed as mg of bilirubin conjugated per g of protein per h. INH, RMP, PAS and hydrocortisone induced UDP-GT activity to a statistically significant degree. The optimum dose for high induction was 20 mg for INH, RMP and hydrocortisone, and 200 mg for PAS per kg of body weight. The optimum time of treatment for high induction was 10 consecutive days of intraperitoneal administration for all drugs examined. Such data, particularly for INH and RMP, indicate why patients who receive these drugs show no clinical jaundice, although they develop an hepatitis-like disease with elevation of serum transaminase of hepatic origin. This could be the result of stimulation of the hepatic smooth endoplasmic reticulum which produces rapid conjugation and therefore excretion of bilirubin. Similarly, the antituberculous drugs may cause liver dysfunction by inducing other liver enzymes.
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PMID:Augmentation of hepatic uridine-diphosphate glucuronyl transferase activity by antituberculous drugs in hamsters in vivo. 312 48

Histochemical studies of human guanase (guanine deaminase) have seldom been undertaken, in part because of technical difficulties which result in heavy background staining. We reported a modified procedure for histochemical demonstration of guanase in human tissues involving hydrolytic deamination of the substrate guanine to xanthine via guanase, and then oxidation of xanthine to uric acid, with concomitant reduction of nitrotetrazolium blue (NBT). In this report, we describe a modification of this method for cytochemical demonstration of guanase at the fine structural level using yellow tetrazolium in place of NBT for determination of the intracellular distribution of guanase in human hepatocytes. In the hepatocytes, the reaction products were seen to be concentrated in the nucleus, in mitochondria, cisternae of the smooth and/or rough-surfaced endoplasmic reticulum, and lysosomes. The precise locations of the reaction product in the cisternae of the nuclear envelope, chromosomes, and nucleus could not be determined. However, the reaction products in the mitochondria were clearly seen to be located in the spaces of cristae. This information of the intracellular distribution of guanase in normal hepatocytes will be useful in determining the physiological role of this enzyme and in further studies on diseased hepatocytes including those in non-A non-B hepatitis.
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PMID:Cytochemical demonstration of guanase in human liver using yellow tetrazolium. 313 23


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