Toru Shizuma

Molecular analysis of antigenicity and immunogenicity of a vaccine-induced escape mutant of hepatitis B virus

Background: To analyze the mechanisms of mutant escape, we established a murine model of hepatitis B virus (HBV) infection and studied the interaction of the envelope protein of the virion with various kinds of anti-hepatitis B antibody. Methods: Mutation from glycine to arginine at aa145 was introduced into replication-competent DNA of HBV. The resulting mutant HBV DNA was transfected into cultured hepatoma cells and livers of mice using liposome-mediated gene transfer. Then, interactions between the antigenic envelope protein (in culture or in circulation) and anti-hepatitis B antibody were examined. Results: Mutant envelope protein escaped human hepatitis B immunoglobulin, rabbit polyclonal anti-hepatitis B surface antigen (HBsAg) antibody, and monoclonal anti-a antibody in vitro and in vivo. There was a difference in the degree of inhibition between hepatitis B immunoglobulin and the other two antibody types in vitro. Transfection with an HBV construct containing a mutation in the a-loop resulted in levels of HBsAg in circulation and seroconversion to anti-HBs antibody that were similar to those produced by a wild-type construct. Conclusions: The degree of escape by the mutant envelope protein differed according to antibody type. Of the three types of antibody used in this study, HBV immunoglobulin was least affected by mutation in the a-loop. There appears to be no correlation between antigenicity and immunogenicity of the escape mutant, and the a-loop mutant may cause hepatitis with the usual serum viral markers.

Protective effects of fermented rice vinegar sediment (Kurozu moromimatsu) in a diethylnitrosamine-induced hepatocellular carcinoma animal model

Low-dose acetylsalicylic acid has been widely used. We evaluated small bowel and gastric injuries during acetylsalicylic acid administration using video capsule endoscopy and gastroduodenal endoscopy. We also investigated blood flow using contrast-enhanced ultrasonography. Six healthy volunteers were enrolled in this preliminary study. The subjects were administered 100 mg of enteric-coated aspirin daily for 14 days. Video capsule endoscopy and gastroduodenal endoscopy were simultaneously performed before administration and on days 1, 3, 7 and 14. Contrast-enhanced ultrasonography was performed before administration and on day 2, and 8. Video capsule endoscopy after administration of low-dose acetylsalicylic acid revealed small bowel mucosal damages of petechiae and erythema in all cases, and denuded area in one case. The total number of lesions in the small bowel increased according to duration of low-dose acetylsalicylic acid administration. However, the total number of lesions in the stomach peaked on day 3. Contrast-enhanced ultrasonography showed that the time-intensity curve peak value and Areas under the curves after acetylsalicylic acid administration were reduced. We observed not only gastric mucosal injuries but also small intestinal injuries with short-term low-dose acetylsalicylic acid administration. Acetylsalicylic acid administration also caused a decrease in small intestinal blood flow. Contrast-enhanced ultrasonography is useful for evaluation blood flow in the small bowel mucosa.

Clinical Characteristics of Concomitant Systemic Lupus Erythematosus and Primary Biliary Cirrhosis: A Literature Review

Although autoimmune diseases often coexist, concomitant cases of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are uncommon. In this review paper, 34 cases of SLE with concomitant PBC found in English and Japanese scientific literature and Japanese proceedings were reviewed and summarized, including cases with liver dysfunction complicated by SLE. Of the 34 reported concomitant cases of SLE and PBC, 97.1% (33/34) were females, and PBC was diagnosed initially in 69.0% (20/29), except for five cases in which both SLE and PBC were simultaneously diagnosed. Sjögrens syndrome was the most common autoimmune disease complicating concomitant SLE and PBC (23.5%, 8/34). Five deaths have been reported: two elderly patients died of liver failure because of the worsening of PBC, and another two patients died from pulmonary infection associated with SLE pharmacotherapy. It is uncertain whether concomitant cases occur by chance or share a common immunological or genetic basis.

Coexistence of Systemic Lupus Erythematosus and Primary Biliary Cirrhosis

Although autoimmune diseases often coexist, cases of concomitant systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are rare. In this paper, 20 cases of concomitant SLE and PBC in the English and Japanese literature were reviewed and summarized. In concomitant cases of SLE and PBC, PBC was diagnosed first in 68.4% (13/19) of the cases and SLE occurred first in 31.6% (6/19) of the cases, although one case was suspected to have simultaneous onset. There may be no correlation between SLE activity and PBC development. In 20 reported cases of concomitant SLE and PBC, two elderly patients died because of liver failure as a result of worsening PBC, and hepatocellular carcinoma was detected in only one elderly patient.

Autoimmune Hemolytic Anemia Following Influenza Virus Infection or Administration of Influenza Vaccine

Autoimmune hemolytic anemia (AIHA) is caused by hemolysis induced by the reaction of autoantibodies with red blood cells. AIHA is categorized as warm, cold, and mixed types and as primary or secondary. Certain viral infections lead to secondary AIHA; however, AIHA induced by influenza virus infection or the administration of influenza vaccine is infrequent. Here, we review relevant case reports in the English and Japanese literature.

Chlamydophila (Chlamydia) pneumoniaeとの重複初感染が疑われたEpstein-Barr virusによる伝染性単核症の1例

A 26-year-old male was hospitalized with fever and pharyngeal pain. Liver dysfunction and an increase in the percentage of atypical lymphocytes in the peripheral blood were detected. Computed tomography showed pneumonia involving the right lung and synpneumonic pleural effusion. Serum immunological tests showed positive results for Epstein-Barr virus (EBV) viral capsid antigen (VCA) IgM and IgG antibodies and Chlamydophila (Chlamydia) pneumoniae (C. pneumoniae) IgM and IgA antibodies on admission. The pneumonia and pleural effusion were no longer detectable after a week of treatment with starting azithromycin. At 7 weeks after admission, the liver function test results returned to within normal limits, the serum became negative for EBV VCA IgM antibody, the C. pneumoniae IgM antibody titer decreased, and the C. pneumoniae IgA and IgG antibody titers increased. This case was suspected to have infectious mononucleosis caused by primary coinfection with C. pneumoniae and EBV.

Common and specific risk factors for ischemic stroke in elderly: Differences based on type of ischemic stroke and aging

BACKGROUND The risk factors among the types of ischemic stroke (atherothrombotic cerebral infarction: ATI, cardio-embolic infarction: CEI, lacunar infarction: LI) in aged stroke patients have rarely been compared to each other. METHODS We compared the clinical parameters of 300 elderly patients with ischemic stroke, age 65-98years, to 100 age-matched control patients. RESULTS Comparison by parametric test and logistic regression analysis between all 300 and 100 control patients showed higher systolic and diastolic blood pressures (p<0.001, p=0.03), lower estimated glomerular filtration rate (eGFR) (p=0.01), larger cardiothoracic ratio (CTR) (p<0.001), smoking (p<0.01) and possibly poor adherence to anti-hypertensive agents in the ischemic stroke patients (p<0.001). Comparisons among three types (n=100 for each) showed the highest atheromatous risk factors for ATI to be hemoglobin A1c (p=0.01) and low-density lipoprotein (p<0.001) and for CEI to be largest cardiac load, indicated by largest left atrial dimension (p<0.001), and CTR (p<0.001). Triglyceride level was found to be a borderline risk factor for LI (p=0.054). Comparison between those aged <74 versus ≥75years (n=150 for each) showed a lower eGFR (p=0.02) and larger right atrial dimension (p<0.001) in patients ≥75. CONCLUSION The risk factors were quite different among the subtypes and aging.

Liver Complications Associated with Systemic Lupus Erythematosus

Although liver dysfunction is not considered the main organ pathology or prognostic factor in patients with Systemic Lupus Erythematosus (SLE), it is not uncommon during the course of SLE. Liver complications in patients with SLE may be caused by lupus hepatitis (SLE-related hepatitis); autoimmune liver diseases, such as Autoimmune Hepatitis (AIH) and Primary Biliary Cirrhosis (PBC); viral hepatitis; and drug-induced liver injury. Here, liver complications in patients with SLE are reviewed.

Pernicious Anemia in Patients with Primary Biliary Cirrhosis, Autoimmune Hepatitis, and Chronic Viral Hepatitis

Backgrounds: Cases of Pernicious Anemia (PA) with Autoimmune Liver Diseases (ALDs) or chronic viral hepatitis have been uncommon. There have been few articles regarding the associations between these diseases. Methods: A review of concomitant cases of PA in patients with ALDs, such as Auto Immune Hepatitis (AIH) or Primary Biliary Cirrhosis (PBC), and patients with chronic viral hepatitis with or without Interferon (IFN) treatment were conducted. Results: Six cases of concomitant PA and ALDs (five were PBC and one was AIH) and seven cases of chronic viral hepatitis (six were due to HCV, one was due to HBV; five cases were of IFN-induced PA and two were of PA without IFN treatment) have been reported. In these concomitant cases, serum vitamin B12 deficiency was documented in all 13 cases and serum Intrinsic Factor Antibodies (IFA) were positive in 11 of 12 cases, excluding one case in which detection of IFA was not mentioned. Conclusions: Although concomitant cases of PA in patients with ALDs or chronic viral hepatitis have been rarely reported, PA should be considered in cases of progressive macrocytic anemia in these patients.

Concomitant Immune Thrombocytopenic Purpura and Crohn's Disease

The coexistence of immune (idiopathic) thrombocytopenic purpura (ITP) and Crohn’s disease (CD) is rare. We performed a review of cases of concomitant ITP and CD in the English and Japanese literature. Among 17 identified cases of concomitant ITP and CD, ITP was initially diagnosed in four cases and CD was initially diagnosed first in six cases. Simultaneous diagnoses were reported in the remaining seven cases. No fatalities were reported in any of the 17 cases. However, resistance or transient responses to standard therapies, such as glucocorticoids or intravenous immunoglobulin (IVIG), and splenectomy for the treatment of ITP were reported in a number of concomitant cases. Moreover, the administration of anti-tumor necrosis factor (TNF)-alpha antibodies was a commonly considered pharmacological therapy in cases of concomitant ITP and CD.