Autoimmune Cholangitis: Is It an Antimitochondrial Antibody Negative Primary Biliary Cirrhosis?

Autoimmune cholangitis/cholangiopathy (AIC) is a recently described disease characterized by chronic cholangitis resembling primary biliary cirrhosis (PBC) with a high frequency of antinuclear antibodies (ANA) and with sero-negativity for antimitochondrial antibodies (AMA). Whether AIC is a disease entity distinct from PBC and autoimmune hepatitis (AIH) or whether it is an AMAnegative variant of PBC or a cholangiopathic variant of AIH have so far been controversial. We recently examined the specificities of AMA and ANA in Japanese patients with AIC, PBC and AIH by immunofluorescence, immunoblotting and enzyme inhibition assays using various mitochondrial and nuclear autoantigens including 2-oxoacid dehydrogenase complex, Sp100, gp210, and p62, and found that AIC and PBC had similar patterns of immunoreactivity. However, this duo is of interest because, usually, among sets of autoimmune syndromes, differences in serological targetting are matched by differences in clinical presentation: AIC and PBC seem to be an exception to this rule. While it is true that a single etiological agent can produce a wide range of disease expression, it is possible that seemingly similar clinicopathological features can be induced by pathogenetic mechanisms caused by a diversity of etiological agents

高齢脳卒中リハビリテーション患者におけるMini Nutritional Assessment Short-FormとGeriatric Nutritional Risk Indexの併存的および予測的妥当性

Background: Malnutrition might worsen the clinical outcomes in stroke patients, although few nutritional screening tools have assessed their validity. Methods: We assessed clinical data of consecutive stroke patients aged ≥65 years in rehabilitation hospital from 2015 to 2017 using the Mini Nutritional Assessment Short-Form (MNA-SF) and the Geriatric Nutritional Risk Index (GNRI) for index testing. The European Society for Parenteral and Enteral Nutrition diagnostic criteria for malnutrition (ESPEN-DCM) was used as a reference standard. The receiver-operating characteristics curve was illustrated by the sensitivity (Se) and specificity (Sp). The Youden index was used to define the cut-off value for malnutrition detection or screening. The Functional Independence Measure (FIM) and discharge destination were compared for verifying predictive validity. Results: We enrolled 420 patients for the analysis. Of them, 125 patients were included in malnutrition group (mean age: 80 years) and 295 in non-malnutrition group (mean age: 77 years) by the ESPEN-DCM. The area under the curve of the MNA-SF and the GNRI were 0.890 and 0.865, respectively. Se and Sp cut-off values to detect or screen malnutrition were 5 (Se: 0.78; Sp: 0.85) and 7 (Se: 0.96; Sp: 0.57) for the MNA-SF and 92 (Se: 0.74; Sp: 0.84) and 98 (Se: 0.93; Sp: 0.50) for the GNRI, respectively. The GNRI were associated with discharge destination, whereas no correlation was observed between the MNA-SF and outcomes by multivariable analysis. Conclusions: The MNA-SF and GNRI have fair concurrent validity if appropriate cut-off values were used. The GNRI exhibits good predictive validity in stroke patients

Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet

Background: Recently, we established a novel rodent model of nonalcoholic steatohepatitis (NASH) with advanced fibrosis induced by a high-fat and high-cholesterol (HFC) diet containing cholic acid (CA), which is known to cause hepatotoxicity. The present study aimed to elucidate the direct impact of dietary CA on the progression of NASH induced by feeding the HFC diet. Methods: Nine-week-old male Sprague–Dawley rats were randomly assigned to receive a normal, HFC, or CA-supplemented (0.1%, 0.5% or 2.0%, w/w) HFC diet for 9 weeks. Results: Histopathological assessment revealed that the supplementation of CA dose-dependently aggravated hepatic steatosis, inflammation, and fibrosis, reaching stage 4 cirrhosis in the 2.0% CA diet group. In contrast, the rats that were fed the HFC diet without any added CA developed mild steatosis and inflammation without fibrosis. The hepatic cholesterol content and mRNA expression involved in inflammatory response and fibrogenesis was higher in a CA dose-dependent manner. The hepatic chenodeoxycholic acid levels were higher in 2.0% CA diet group than in the control, although hepatic levels of total bile acid and CA did not increase dose-dependently with CA intake. Conclusion: Adding CA to the HFC diet altered bile acid metabolism and inflammatory response and triggered the development of fibrosis in the rat liver

A non-obese, diet-induced animal model of nonalcoholic steatohepatitis in Wistar/ST rats compared to Sprague-Dawley rats

Background: Non-alcoholic steatohepatitis (NASH), a subtype of non-alcoholic fatty liver disease (NAFLD), is a potentially progressive liver disease that can lead to cirrhosis. Obesity increases the risk of NAFLD/NASH, but this disease can also be observed in non-obese individuals. Methods: We investigated the metabolic and histopathological changes in 13 obesity-resistant Slc:Wistar/ST rats fed a high-fat and high-cholesterol (HFC) diet for 9 weeks, and also retrospectively compared the results of 41 Sprague-Dawley (SD) rats that were previously fed with the same protocol to the results of the Slc:Wistar/ST rats. Results: Of the 13 Slc:Wistar/ST rats fed an HFC diet containing 1.25% or 2.5% cholesterol, 11 (84.6%) developed histologically proven NASH without obesity, an increased visceral fat volume, insulin resistance, histopatological severe lobular inflammation and severe hepatic fibrosis. The HFC diets significantly increased the levels of mRNA encoding collagen type I alpha 1 (COL1A1), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). The SD rats also developed NASH without obesity, an increased visceral fat volume and insulin resistance, but the metabolic and histopathological effects, such as lower serum adiponectin levels, higher serum leptin levels, histopatological severe lobular inflammation and hepatic fibrosis, seemed to be more pronounced in the SD rats than in the Slc:Wistar/ST rats. Conclusions: These two rat models may reflect the human etiology of NASH that is influenced by dietary factors, and the obesity-resistant Slc:Wistar/ST rat model may be particularly useful for elucidating the pathophysiological mechanism of the so-called “lean NASH”

The sperm mitochondria-specific translocator has a key role in maternal mitochondrial inheritance.

The mechanism of maternal mitochondrial inheritance in animals involves the selective elimination of sperm mitochondria by the elimination factor of the egg and the sperm mitochondria-specific factor. In vitro fertilization using sperm from isogenic mice incorporating heterospecific mitochondrial DNA (mtDNA) showed that the number of PCR positives of sperm mtDNA in two-cell embryos was significantly increased following sperm incubation with anti-tetratricopeptide repeat-containing protein involved in spermatogenesis (tpis) protein, anti-translocator of mitochondrial outer membrane (Tom) 22 and anti-Tom40 antibodies. The treatment of fertilized eggs with EGTA and other endonuclease inhibitors increased the sperm mtDNA levels. We conclude that the elimination factor, which is probably an endonuclease, is selectively received by the tpis protein of the sperm mitochondrial outer membrane within the egg. It is then transported into the sperm mitochondria by Tom22 and Tom40, where it destroys the sperm mtDNA, establishing the maternal inheritance of mtDNA.The Version of Record (VoR) is available at http://www.cellbiolint.or

Endoscopic Polypectomy of Esophageal Leiomyomas; Report of Two Cases

We describe esophageal leiomyomas in two young patients (aged 35 and 32 years), who complained of dysphagia and epigastralgia, which were successfully treated by endoscopic polypectomy. Upper endoscopy showed a pedunculated polyp beneath the normal mucosa located at 28 cm from the incisor in the first case and 1 cm sessile 2.1 cm semipedunculated polypoid lesion in the lower esophagus just above the esophageal-gastric junction in the second case. Both lesions were resected by snare polypectomy without any complication. Light microscopic examination and immunohistochemistry of the tumor tissue confirmed the diagnosis of leiomyoma. Endoscopic polypectomy of esophageal leiomyoma is safe and should be considered as an optional treatment modality whenever possible

A Case of Autoimmune Hepatitis Associated with Idiopathic Thrombocytopenic Purpura and Chronic Thyroiditis

Autoimmune hepatitis (AIH) is frequently associated with extrahepatic autoimmune disorders such as rheumatoid arthritis, Sjogren\u27s syndrome, and chronic thyroiditis, but the association with idiopathic (immune) thrombocytopenic purpura (ITP) is rare. We report a 46-year-old Japanese woman who presented with severe thrombocytopenia, elevated levels of aminotransferases, immunoglobulin (Ig) G, and platelet-associated IgG (PAIgG), positive anti-nuclear antibody, and hypothyroidism. After a diagnosis of coexisting AIH, ITP, and chronic thyroiditis, the patient was treated with 30 mg/day of prednisolone orally. The patient responded to such treatment: showing an increase in the number of platelets and decrease of serum levels of aminotransferases, IgG, and PAIgG to within normal ranges. Discrimination of ITP from liver cirrhosis as a cause of severe thrombocytopenia seen in chronic liver disease is important because complications and therapy are quite different. Prednisolone as a treatment for All should be also effective for ITP, and therefore, ITP should be considered when liver dysfunction is accompanied by severe thrombocytopenia, particularly in the autoimmune types of liver diseases

Response to Urinary Trypsin Inhibitor Therapy in Ulcerative Colitis is Associated With a Decrease in Mast Cell Count in the Colonic Mucosa

BACKGROUND: Urinary trypsin inhibitor (UTI, ulinastatin (R)) inhibits proteinases and has been used for the treatment of ulcerative colitis (UC). We investigated the therapeutic effect of UTI in patients with UC and correlated this effect to mast cell (MC) and macrophages (M) counts in the colonic mucosal wall. DESIGN: Patients with UC resistant to corticosteroids (n=16) and normal control subjects (n=10) were included in this study. Biopsy specimens obtained from the sigmoid colon of patients before and after UTI therapy were immunostained with antibodies to tryptase (AA1, MC) and CD68 (M). The number of MC and M in the lamina propria (LP) was determined and expressed per mm2 of LP. RESULTS: Nine patients with UC responded to UTI treatment. The mean number of MC in the upper part of LP in responders(440ﾂｱ51/mm2)was higher than nonresponders (312ﾂｱ76/mm2)and normal controls(200ﾂｱ47/mm2). MC counts in the lower part of the LP were not different in responders and nonresponders, although the counts in both groups were significantly higher than control. The number of M in the lower part of LP was similar in responders and nonresponders, but were higher than control subjects. M counts in the upper part of LP were similar in both groups of patients and control. Effective treatment with UTI in responders was associated with a significant fall in the number of MC in the upper layer of LP but not in M. CONCLUSION. Our results showed that UTI is an effective therapy in steroid-resistant UC. Our results also showed effective therapy with UTI was associated with a reduction in MC counts in the colonic mucosa, suggesting that the control of these cells may mediate, at least in part, the therapeutic effects of UTI in UC

Spontaneous Regression of Colonic Lesions in Adult T-cell Leukemia

A 74-year-old man was admitted to our hospital because of diarrhea. Serum anti-HTLV-1 antibody was positive without abnormal lymphocytes. Colonoscopy demonstrated a edematous and congested mucosa with erosions, and ulcers in the region extending from the cecum to rectum. Biopsy specimens showed diffuse infiltration of abnormal lymphocytes positive for T-cell markers in the lamina propria. Conservative therapy was provided but no chemotherapy because of improvement of diarrhea within two weeks. A repeat colonoscopy 6 months later revealed scars without erosions or ulcers. Eight months after first admission, the patient was readmitted to our hospital because of acute ATL crisis, and died of hepatic involvement 7 days later. Colonic lesions associated with ATLS may show spontaneous regression and recurrence