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Zhongguo Dang Dai Er Ke Za Zhi =... Jul 2017Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Δ4-3-oxo-steroid...
Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Δ4-3-oxo-steroid 5β-reductase. Cholestatic jaundice is the main clinical manifestation, accompanied by malabsorption of fat and fat-soluble vitamins. This paper reported the clinical and genetic features of a CBAS2 patient definitely diagnosed by AKR1D1 genetic analysis. An 8-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 7 months. On physical examination, growth retardation and malnutrition were discovered besides mild jaundice of the skin and sclera. The liver was palpable 8 cm below the right subcostal margin with medium texture, and the spleen was not enlarged. On liver function test, elevated levels of bilirubin (predominantly conjugated bilirubin) and transaminases were detected, but serum total bile acids and γ-glutamyl transpeptidase levels were within the normal ranges. Liver histopathologic analysis showed disorganized bile ducts, obvious multinucleated giant cells, significant cholestasis in hepatocytes, together with portal and interstitial fibrosis and lymphocytic infiltration. Via next generation sequencing analysis and Sanger sequencing confirmation, the infant proved to be a compound heterozygote of the AKR1D1 variants c.579+2delT and c.853C>T(p.Q285X), two novel mutations originated from his mother and father, respectively. CBAS2 was thus definitely diagnosed, and chenodeoxycholic acid was given orally. As a result, the abnormal liver function and hepatomegaly were improved gradually. On a follow-up 3 months later, a soft liver was palpable 2.5 cm below the right subcostal margin, and all liver function indices recovered to normal ranges.
Topics: Bile Acids and Salts; Cholestasis; Humans; Infant; Liver; Male; Mutation; Oxidoreductases; Steroid Metabolism, Inborn Errors
PubMed: 28697823
DOI: 10.7499/j.issn.1008-8830.2017.07.002 -
Diabetes Jun 2002Sterol regulatory element binding protein-1c (SREBP-1c) is a transcription factor that mediates insulin effects on hepatic gene expression. It is itself... (Comparative Study)
Comparative Study
Sterol regulatory element binding protein-1c expression and action in rat muscles: insulin-like effects on the control of glycolytic and lipogenic enzymes and UCP3 gene expression.
Sterol regulatory element binding protein-1c (SREBP-1c) is a transcription factor that mediates insulin effects on hepatic gene expression. It is itself transcriptionally stimulated by insulin in hepatocytes. Here we show that SREBP-1c mRNA is expressed in adult rat skeletal muscles and that this expression is decreased by diabetes. The regulation of SREBP-1c expression was then assessed in cultures of adult muscle satellite cells. These cells form spontaneously contracting multinucleated myotubes within 7 days of culture. SREBP-1c mRNA is expressed in contracting myotubes. A 4-h treatment with 100 nmol/l insulin increases SREBP-1c expression and nuclear abundance by two- to threefold in myotubes. In cultured myotubes, insulin increases the expression of glycolytic and lipogenic enzyme genes and inhibits the 9-cis retinoic acid-induced UCP3 expression. These effects of insulin are mimicked by adenovirus-mediated expression of a transcriptionally active form of SREBP-1c. We conclude that in skeletal muscles, SREBP-1c expression is sensitive to insulin and can transduce the positive and negative actions of the hormone on specific genes and thus has a pivotal role in long-term muscle insulin sensitivity.
Topics: Alitretinoin; Animals; Blotting, Northern; CCAAT-Enhancer-Binding Proteins; Carrier Proteins; Cells, Cultured; DNA-Binding Proteins; Diabetes Mellitus, Experimental; Gene Expression; Gene Expression Regulation; Glycolysis; Insulin; Ion Channels; Lipids; Liver; Male; Mitochondrial Proteins; Muscle Contraction; Muscle, Skeletal; Protein Isoforms; RNA, Messenger; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Transfection; Tretinoin; Uncoupling Protein 3
PubMed: 12031958
DOI: 10.2337/diabetes.51.6.1722 -
Canadian Liver Journal 2021Giant cell hepatitis (GCH) is a rare entity in adults that is characterized by large multinucleated hepatocyte formation and parenchymal inflammation. We present a case...
Giant cell hepatitis (GCH) is a rare entity in adults that is characterized by large multinucleated hepatocyte formation and parenchymal inflammation. We present a case of acute liver failure in a 33-year-old woman secondary to autoimmune hepatitis (AIH). A liver biopsy revealed submassive hepatocyte necrosis consistent with GCH. We conducted a literature review of 187 reported cases of post-infantile GCH in adults. AIH was the most commonly reported cause of GCH, but GCH was associated with a wide spectrum of etiologies, including infections, rheumatological diseases, hematological diseases, malignancies, and medications. The severity of disease can range from mild hepatitis to fulminant hepatic failure. The mortality rate among the cases in the literature was 18.82%. GCH is managed by treating the underlying cause, and ribavirin has been proposed as a treatment option for idiopathic GCH. A small number of patients progress to requiring orthotopic liver transplant, but recurrence is possible post-transplant.
PubMed: 35991767
DOI: 10.3138/canlivj-2020-0024 -
World Journal of Clinical Cases Sep 2021The immune-mediated invasion of IgG4-positive plasma cells in the liver is found in some autoimmune hepatitis. Giant-cell hepatitis (GCH) is a very rare pathological...
BACKGROUND
The immune-mediated invasion of IgG4-positive plasma cells in the liver is found in some autoimmune hepatitis. Giant-cell hepatitis (GCH) is a very rare pathological feature in adults, and the clinical characteristics of the simultaneous appearance of the two pathological phenomena are not clear.
CASE SUMMARY
A 68-year-old woman was hospitalized with fatigue, poor appetite, and yellow urine for 20 d. Liver function tests and immunological indexes were significantly abnormal and accompanied by elevated serum IgG4 levels. Liver pathology revealed severe inflammation of the interface between the portal tract and hepatocytes, portal area inflammation, plasma cell infiltration, formation of rosette cells, IgG4-positive plasma cells > 10/high-power field, IgG4/IgG > 40%, and multinucleated liver cell swelling. IgG4-related autoimmune hepatitis (AIH) combined with GCH was diagnosed, and methylprednisolone was administered at 40 mg/day. Two weeks later, the clinical symptoms disappeared, and the liver function and immunological indicators were significantly improved. Methylprednisolone was reduced at a rate of 4-8 mg per week to 8 mg/day for maintenance. A second liver biopsy 48 wk later indicated that liver inflammation and fibrosis were significantly improved. IgG4-positive plasma cells and GCH were not detected. A literature search was conducted to analyze articles reporting similar pathological phenomena.
CONCLUSION
AIH with simultaneous IgG4-positive plasma cell infiltration and GCH, liver inflammation, and fibrosis is possibly more severe than typical AIH but sensitive to corticosteroids.
PubMed: 34616822
DOI: 10.12998/wjcc.v9.i25.7527 -
BMC Gastroenterology Jul 2014Staphylococcus epidermidis is the most frequently isolated species of the coagulase negative staphylococci from human stool. However, it is not clear how its presence in...
BACKGROUND
Staphylococcus epidermidis is the most frequently isolated species of the coagulase negative staphylococci from human stool. However, it is not clear how its presence in the gut affects the cellular structures and functions of this organ. In this study therefore, the pathogenicity of strains of S. epidermidis which were isolated from the stool samples of apparently healthy children was investigated in mice and rats.
METHODS
The albino mice (22-30 g) and albino rats (100-155 g) of both sexes were infected orally and intraperitoneally with graded doses of the bacteria and subjected to behavioral and histopathological examinations.
RESULTS
Acute infection in these animals caused temporary behavioural changes as shown by restlessness and abdominal stretchings but did not result in death even at a dosage of 2 × 109 cfu/kg. Daily administration of the same dose for 14 days resulted in the death of 11 out of 21 (52.4%) mice. Histopathological examination of the affected organs showed congestions, aggregations and multinucleated hepatocytes in the liver, infiltration of the kidney tubule interstitial by chronic inflammatory cells, coagulative necrosis of the kidney, spleen, intestine and stomach cells as well as marked stroma fibrosis of the spleen. Coagulative necrosis of cells was the most frequently occurring pathological alteration. Lethality and pathological effects reflected the virulence factors expressed by the organism which are biofilm formation, haemagglutination properties and capsule production.
CONCLUSIONS
The results indicate that strains of S. epidermidis colonising the gut can cause serious pathological changes on certain organs such as kidney, liver, intestine, stomach and spleen which, depending on their severity, could be fatal.
Topics: Animals; Behavior, Animal; Female; Gastrointestinal Tract; Humans; Kidney; Liver; Male; Mice; Rats; Spleen; Staphylococcal Infections; Staphylococcus epidermidis; Virulence
PubMed: 25016472
DOI: 10.1186/1471-230X-14-126 -
International Journal of Clinical and... 2020The function of Interleukin-6 (IL-6) in the regenerative process is not fully understood. The aim was to show the IL-6 role in hepatocyte regeneration by identifying the...
INTRODUCTION
The function of Interleukin-6 (IL-6) in the regenerative process is not fully understood. The aim was to show the IL-6 role in hepatocyte regeneration by identifying the proliferative rate of hepatocytes following partial hepatectomy.
MATERIAL AND METHODS
Eighty male adult Sprague-Dawley rats were categorized into two equivalent groups (n = 40 rats); non-treated, and treated group with IL-6 of 35 µg/100 gm body weight according to lethality study for a four-day observation. Both groups were subjected to 70% hepatic resection. Liver specimens were taken for histo/immunohistochemical studies. Five measures were investigated histopathologically; binucleation, mitoses, thickening of the hepatic plate, ductular reaction, and presence of inflammatory cells. Ki-67 labeling index was evaluated using mouse anti-Ki-67 antibody.
RESULTS
In non-treated group; binucleation and multinucleation were noted in 12 cases (30%), bizarre cells with abnormal mitoses 16 cases (42%), and thickening of liver cell plate 18 cases (45%), in contrast to 32 (80%), 30 (75%) and 28 (70%), in treated group. Patches of inflammatory infiltrate were more marked in the treated group. Ki-67 labeling index was higher in the treated group (-value 0.00001). The degree of Ki-67 reactivity in the treated group was: negative 6 (15%), weak 6 (15%), moderate 16 (40%) and strong 12 (30%) compared with 18 (45%), 13 (32.5%), 6 (15%) and strong 3 (7.5%) in non-treated group.
CONCLUSION
IL-6 is valuable in the induction of liver cell regeneration. Correlation with biochemical assay and flow cytometric studies is recommended.
PubMed: 32782672
DOI: No ID Found -
Human Pathology Nov 1991In a retrospective study we assessed the hepatic changes in children with the acquired immunodeficiency syndrome by reviewing 12 biopsy specimens and 48 autopsy...
In a retrospective study we assessed the hepatic changes in children with the acquired immunodeficiency syndrome by reviewing 12 biopsy specimens and 48 autopsy specimens from 54 children. Hepatopathology differed in biopsy and autopsy material. In biopsy specimens, chronic active hepatitis with predominantly T8 lymphocytes by tissue immunochemistry was common (five of 12 specimens). Fatty degeneration and hepatocellular necrosis were either absent, mild, or patchy. On the other hand, at autopsy, chronic active hepatitis was not observed. The most prominent changes were extensive fatty degeneration, nonspecific portal mononuclear infiltration, portal fibrosis, and confluent (ischemic) necrosis. Opportunistic infections such as Mycobacterium avium-intracellulare (MAI) were noted only at autopsy. In addition, three unusual morphologic characteristics were noted: nodular lymphoplasmacytic portal infiltrate, a pseudosarcomatous variant of Mycobacterium avium-intracellulare infection, and multinucleated giant cells (foreign both type and giant cell transformation of hepatocytes).
Topics: Acquired Immunodeficiency Syndrome; Adolescent; Autopsy; Biopsy; Child; Child, Preschool; Giant Cells; Humans; Infant; Liver Diseases; Retrospective Studies
PubMed: 1743694
DOI: 10.1016/0046-8177(91)90263-o -
National Toxicology Program Technical... Nov 2010Dioxin Toxic Equivalency Factor Evaluation Overview- Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to...
UNLABELLED
Dioxin Toxic Equivalency Factor Evaluation Overview- Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds"(DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized they accumulate in adipose tissue resulting in chronic lifetime human exposure. Since human exposure to DLCs always occurs as a complex mixture, the toxic equivalency factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally related polychlorinated biphenyls (PCBs) and mixtures of these compounds. Polychlorinated biphenyls (PCBs) and their mixtures including 2,3',4,4',5-pentachlorobiphenyl (PCB 118) were produced commercially before 1977 for the electric industry as dielectric insulating fluids for transformers and capacitors. Manufacture and use of these chemicals were stopped because of increased PCB residues in the environment, but they continue to be released into the environment through the use and disposal of products containing PCBs, as by-products during the manufacture of certain organic chemicals, during combustion of some waste materials, and during atmospheric recycling. This PCB 118 study was conducted as part of the dioxin TEF evaluation that included multiple 2-year rat bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLCs, structurally related PCBs, and mixtures of these compounds. Female Harlan Sprague-Dawley rats were administered PCB 118 (at least 99% pure) in corn oil:acetone (99:1) by gavage for 14, 31, or 53 weeks or 2 years. 2-YEAR STUDY: Groups of 80 female rats were administered 100, 220, 460, 1,000, or 4,600 g PCB 118/kg body weight in corn oil:acetone (99:1) by gavage, 5 days per week, for up to 105 weeks; a group of 80 vehicle control female rats received the corn oil/acetone vehicle alone. Groups of 30 female rats received 10 or 30 g/kg for up to 53 weeks only. Up to 10 rats per group were evaluated at 14, 31, or 53 weeks. A stop-exposure group of 50 female rats was administered 4,600 g/kg PCB 118 in corn oil:acetone (99:1) by gavage for 30 weeks then the vehicle for the remainder of the study. Survival of all dosed groups of rats was similar to that of the vehicle control group. Mean body weights of 1,000 g/kg rats were 7% less than those of the vehicle controls after week 36, and those of the 4,600 g/kg core study and stop-exposure groups were 7% less than those of the vehicle controls after week 7. Following cessation of treatment, the body weight gain in the stop-exposure group was similar to that of the vehicle control group. In general, exposure to PCB 118 lead to dose-dependent decreases in the concentrations of serum total thyroxine (T4) and free T4 in all dosed groups. There were no effects on triiodothyronine or thyroid stimulating hormone levels in any dosed groups evaluated at the 14-, 31-, and 53-week interim evaluations. There were increases in hepatic cell proliferation in the 4,600 g/kg group at 14, 31, and 53 weeks. Administration of PCB 118 led to dose-dependent increases in CYP1A1-associated 7-ethoxyresorufin-O-deethylase, CYP1A2-associated acetanilide4-hydroxylase, and CYP2B-associated pentoxyresorufin-O-deethylase activities at the 14-, 31-, and 53-week interim evaluations. Analysis of PCB 118 concentrations in dosed groups showed dose- and duration of dosing-dependent increases in fat, liver, lung, and blood. The highest concentrations were seen in fat at 2 years with lower concentrations observed in the liver, lung, and blood. At the 53-week interim evaluation, three 4,600 g/kg rats had liver cholangiocarcinoma and one had hepatocellular adenoma. At 2 years, there were significant treatment-related increases in the incidences of cholangiocarcinoma and hepatocellular adenoma. Four incidences of hepatocholangioma occurred in the 4,600 g/kg core study group. At 2 years, a significant dose-related increase in hepatic toxicity was observed and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, inflammation, oval cell hyperplasia, pigmentation, multinucleated hepatocyte, eosinophilic and mixed cell foci, diffuse fatty change, toxic hepatopathy, nodular hyperplasia, necrosis, bile duct hyperplasia and cyst, and cholangiofibrosis. The incidences of these lesions were often decreased in the 4,600 g/kg stop-exposure group compared to the 4,600 g/kg core study group. In the lung at 2 years, a significantly increased incidence of cystic keratinizing epithelioma occurred in the 4,600 g/kg core study group compared to the vehicle control group incidence. Incidences of bronchiolar metaplasia of the alveolar epithelium were significantly increased in the groups administered 460 g/kg or greater, and the incidence of squamous metaplasia was significantly increased in the 4,600 g/kg core study group. The incidence of carcinoma of the uterus in the 4,600 g/kg stop-exposure group was significantly greater than those in the vehicle control and 4,600 g/kg core study groups at 2 years. A marginal increase in squamous cell carcinoma occurred in the 220 g/kg group. At 2 years, there were marginally increased incidences of exocrine pancreatic adenoma or carcinoma in the 460, 1,000, and 4,600 g/kg core study groups. Numerous nonneoplastic effects were seen in other organs including: adrenal cortical atrophy and cytoplasmic vacuolization, pancreatic acinar cell cytoplasmic vacuolization and arterial chronic active inflammation, follicular cell hypertrophy of the thyroid gland, inflammation and respiratory epithelial hyperplasia of the nose, and kidney pigmentation.
CONCLUSIONS
Under the conditions of this 2-year gavage study, there was clear evidence of carcinogenic activity of PCB 118 in female Harlan Sprague-Dawley rats based on increased incidences of neoplasms of the liver (cholangiocarcinoma, hepatocholangioma, and hepatocellular adenoma) and cystic keratinizing epithelioma of the lung. Occurrences of carcinoma in the uterus were considered to be related to the administration of PCB 118. Occurrences of squamous cell carcinoma of the uterus and acinar neoplasms of the pancreas may have been related to administration of PCB 118. Administration of PCB 118 caused increased incidences of nonneoplastic lesions in the liver, lung, adrenal cortex, pancreas, thyroid gland, nose, and kidney. Synonyms: 1,1'-Biphenyl, 2,3',4,4',5-pentachloro-(9CI); 1,1'-biphenyl, 2,3',4,4',5-pentachloro-; 2,3',4,4',5-pentachloro-1,1'-biphenyl; 2,4,5,3',4'-pentachlorobiphenyl; 3,4,2',4',5'-pentachlorobiphenyl; biphenyl, 2,3',4,4',5-pentachloro-; CB 118.
Topics: Animals; Carcinogenicity Tests; Dose-Response Relationship, Drug; Female; Humans; Male; Neoplasms, Experimental; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Rats; Rats, Sprague-Dawley
PubMed: 21383778
DOI: No ID Found -
Poultry Science May 2007Muscle cell proliferation, migration, adhesion, and fusion are processes involved with the formation of multinucleated myotubes that will further differentiate into...
Muscle cell proliferation, migration, adhesion, and fusion are processes involved with the formation of multinucleated myotubes that will further differentiate into mature muscle fibers. The process of muscle fiber development is nearly complete at the time of hatch. Muscle growth during the embryonic period of development is characterized by an increase in myoblast cell number through hyperplasia. Posthatch muscle fiber growth occurs through muscle fiber enlargement by the process of hypertrophy, which results from the recruitment of satellite cell nuclei. Hyperplasia and hypertrophy are regulated by factors extrinsic to the cell. These extrinsic elements include growth factors and the extracellular matrix. The growth factors, hepatocyte growth factor, fibroblast growth factor 2, transforming growth factor-beta, insulin-like growth factor, and myostatin stimulate or inhibit myoblast and satellite cell proliferation and differentiation. Some of these growth factors like fibroblast growth factor 2 must interact with a low affinity extracellular matrix macromolecule to bind to their high affinity receptor necessary for cell signaling. It is probable that the expression of extracellular matrix proteins involved in growth factor signaling will affect muscle growth properties during hyperplasia and hypertrophy. As signaling pathways associated with muscle growth mechanisms are further understood, the poultry industry may find it beneficial to include the expression of key genes in their selection strategies.
Topics: Animals; Chick Embryo; Chickens; Helminthiasis, Animal; Hyperplasia; Hypertrophy; Muscle, Skeletal
PubMed: 17435046
DOI: 10.1093/ps/86.5.1050 -
Parasite Immunology 2004The involvement of inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) in pathogenesis of toxocaral granulomatous hepatitis (TGH) in a murine host was...
The involvement of inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) in pathogenesis of toxocaral granulomatous hepatitis (TGH) in a murine host was quantitatively determined by biochemical, parasitological, pathological, and immunohistochemical assessments in a 42-week investigation. Mice were sacrificed for serum collection and histological processing as well as acid-pepsin digestion of the liver in a larval recovery study. Significantly increased levels of total serum NO were found in the trial, indirectly suggesting iNOS activation in the liver. iNOS reactivity was predominantly observed in infiltrating leucocytes in lesions and normal and apocrine-like cholangiocytes; in contrast, hepatocytes and multinucleated giant cells showed negative cytoplasmic staining in TGH. Strong iNOS-like reactivity was also detected on the body wall of larvae. The locations of NT reactivity were nearly identical to those of iNOS expression; infiltrating leucocytes or cholangiocytes stained for iNOS were also stained for NT in TGH. Enhanced iNOS expression, but not invading larvae (r = 0.256, P = 0.211), seemed to play a certain role in pathological damage in TGH due to a significant correlation between iNOS expression and serum alanine aminotransferase (ALT) levels (r =0.593, P = 0.021) in the trial. Our present results indicate a potential therapeutic strategy for treatment of GH caused by other nematodes through manipulation of iNOS expression.
Topics: Alanine Transaminase; Animals; Female; Giant Cells; Granuloma; Hepatitis, Animal; Hepatocytes; Larva; Leukocytes; Liver; Mice; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Toxocara canis; Toxocariasis; Tyrosine
PubMed: 15541031
DOI: 10.1111/j.0141-9838.2004.00708.x