Role of peptide antigen for induction of inhibitory antibodies to Streptococcus mutans in human oral cavity.

The alanine-rich repeating region (A-region) in the surface protein antigen (PAc) of Streptococcus mutans has received much attention as an antigenic component for vaccines against dental caries. The PAc (residue 361-386) peptide in the A-region possesses a multiple binding motif (L- -V-K- -A) to various HLA-DR molecules and a B-cell core epitope (- Y- - -L- -Y- - - -) that recognizes the inhibiting antibody to S. mutans. In the present study, we investigated the immunogenicity of the PAc (361-386) peptide in humans and regulators of induction of the anti-PAc (361-386) peptide IgA antibody (aPPA) in saliva. The PAc (361-386) peptide was confirmed as an ideal peptide antigen for induction of the inhibiting antibody to S. mutans in 151 healthy human subjects (36.6 +/- 12.6 years old) by quantitative analyses of oral bacteria and ELISA, as the aPPA titre in human saliva decreased significantly in an age-dependent manner. Homozygous DRB1*0405 and 1502, and heterozygous DRB1*0405/1502 showed a negative association with production of aPPA and tended to reduce the number of total streptococci in saliva. In contrast, the DRB1*1501 allele was significantly correlated with a high level of induction of the antibodies, and also tended to reduce lactobacilli and mutans streptococci. Further, peptide immunogenicity was confirmed in NOD-SCID mice grafted with human peripheral blood mononuclear cells. Our results indicate that the interplay between regulators such as age, DRB1 genotype, cytokines, and peptide immunogenicity may provide a potential means for developing a vaccine useful for the prevention of dental caries as well as their diagnosis.

Studies on the relationship between hepatic and splenic density change in dynamic CT in the presence of a large splenorenal shunt in patients with liver cirrhosis.

Using dynamic computerized tomography (CT), we studied liver and spleen hemodynamics in one group of patients with a large splenorenal shunt and another group without a large shunt. Specifically, we measured the time-to-peak hepatic and splenic enhancement and the loss of enhancement, i.e., decay time. The time-to-peak liver enhancement (61 +/- 21 s vs. 81 +/- 14 s, p < 0.05) and the splenic decay time (24 +/- 16 s vs. 48 +/- 28 s, p < 0.05) were significantly shorter in patients with a large splenorenal shunt compared to those without. The groups had similar hepatic decay times and times to peak splenic enhancement. We found dynamic CT useful in assessing the effect of a large splenorenal shunt on portal and splenic hemodynamics.

Evaluation of hepatic density change by dynamic CT in healthy humans and in patients with chronic liver diseases.

Dynamic computed tomography using 0.4 ml/kg of 65% meglumine diatrizoate was performed to estimate pharmacokinetics of contrast media in the liver in healthy controls (N = 11), in patients with chronic viral hepatitis (N = 17), posthepatic liver cirrhosis (N = 21), and alcoholic liver cirrhosis (N = 23). The time of peak enhancement (the time interval between peak aortic and liver enhancement) was significantly different between each group. Alcoholic liver cirrhosis was the most prolonged, followed by posthepatic liver cirrhosis, chronic viral hepatitis, and finally controls. A peak enhancement time of 28 sec had a diagnostic accuracy of 97% for chronic liver diseases. A time greater than 44 sec had a diagnostic accuracy for cirrhosis of 96%. The decay time (the time from peak enhancement of the liver to the curve's center of gravity) was also significantly different between each group. Again, alcoholic liver cirrhosis was the longest, followed by posthepatic liver cirrhosis, chronic viral hepatitis, and then the controls. Dynamic computed tomography has many potential applications in studying intrahepatic physiologic events and may contain diagnostic information for chronic liver diseases.

[Studies on the mode of progression of alcoholic liver disease].

In order to elucidate the mode of progression of alcoholic liver disease, relationships among the drinking style, laboratory data, anti-HCV antibody and histological changes were investigated on 36 patients in whom the liver biopsy was repeatedly done. Following results were obtained (1) In the group of continuous drinking over 100g ethanol per day, histological progression was found in 11 of 13 patients (85%) regardless of positive anti-HCV. On the other hand, in the group of abstinence or temperance less than 60g daily alcohol intake, histological improvement was found in 6 of 11 patients (55%). (2) Histological improvement was predominantly seen by abstinence or temperance in the cases with lower levels of serum IgA and adenosine deaminase (ADA) on hospitalization and those with rapid decrease in serum gamma-GTP after hospitalization. In conclusion, the amount of ethanol was considered to be the most important factor to affect on a progression of alcoholic liver diseases. Assessment of laboratory data such as IgA and ADA on hospitalization and change in gamma-GTP after hospitalization were also thought to be useful in foreseeing the prognosis of alcoholic liver disease.

[Influence of hepatitis C virus on the alcoholic liver diseases].

In order to know the influence of hepatitis C virus (HCV) on the alcoholic liver diseases (ALD), 124 patients with ALD were divided into two groups by positive or negative anti-HCV, and differences of histological findings, laboratory data, evolution of histopathology and liver disease of those who developed hepatocellular carcinoma (HCC) between both groups were investigated. There were 31 patients (25%) in the anti-HCV positive group and 93 patients (75%) in the negative group. Histologically, viral changes were seen in most patients (55%) of the positive group, whereas those were seen in a few patients (15%) of the negative group. The patients of the positive group showed higher serum adenosine deaminase levels compared with those of the negative group. However, as regards the evolution of histopathology, amount of alcohol consumed seemed to be more responsible than positive anti-HCV. Three out of 6 patients with HCC were anti-HCV positive cirrhotics, although there were three anti-HCV negative HCC patients: one with cirrhosis and two with hepatic fibrosis.

[Positive rate of serum anti-HCV in various liver diseases and the clinico-pathological study of chronic liver disease in alcoholics].

The aim of this study was to elucidate the positive rate of serum anti-HCV in alcoholic (with negative HBsAg and without blood transfusion history) and non-alcoholic (type-B and type-NANB) patients with chronic liver diseases. The clinico-pathological difference between anti-HCV positive and negative alcoholic patients was also investigated. Anti-HCV (Chiron C-100-3) was assayed with Ortho EIA kit in 196 patients. Liver function tests and the histological findings were evaluated in 111 cases of chronic hepatitis (CH) and 39 of liver cirrhosis (LC). Following results were obtained. [1] Positive rate of serum anti-HCV in alcoholic patients was 40% in CH, 36% in LC and 100% in hepatocellular carcinoma. In non-alcoholic type-NANB group, it was 75%, 68% and 69%, respectively. [2] Serum GGT/ALT ratio was higher in anti-HCV negative patients than positive patients both in CH and LC alcoholics. In non-alcoholic group, it was higher in type-NANB patients than type-B patients. [3] Among the histological findings in CH alcoholics, lymph follicles in the portal area were characteristic in anti-HCV positive patients, while these were not seen in negative patients. [4] In LC alcoholics, regenerative nodules were irregular in size in anti-HCV positive patients, while these were even and small in negative patients. [5] Serum HCV-RNA was detected in two out of 14 anti-HCV negative patients. [6] A female alcoholic patient who showed positive serum anti-HCV and negative HCV-RNA was presented. [7] For the evaluation of the influence of HCV in alcoholics, further studies have to be continued with more sensitive HCV markers.

Incidence of ultrasound-detected intrahepatic hematomas due to Tru-cut needle liver biopsy.

This is a prospective study in which 120 patients with diffuse liver disease undergoing liver biopsy were followed by serial ultrasounds to determine the incidence of postbiopsy intrahepatic hematoma formation. Forty-five of the patients had a blind biopsy, while the remaining 75 patients had a biopsy performed during laparoscopy. In both groups a 2.0-mm Tru-cut needle was employed. The overall incidence of postbiopsy hematoma formation was 18.3%, with approximately the same results occurring in blind biopsy patients (20%) and laparoscopy-guided biopsy patients (17%). Only two patients had significant pain associated with the hematoma formation (one from each group), one of whom had evidence of intraperitoneal bleed and rebleed. Our results suggest that postbiopsy asymptomatic hematomas occur more frequently than had been generally thought and that laparoscopy-guided biopsy is not safer than blind biopsy.

Peritoneoscopic examination using intravenous administration of indocyanine green in the fatty liver.

Forty patients with fatty liver were studied by peritoneoscopic examination after intravenous administration of indocyanine green (ICG). Although diffuse or centrilobular steatosis was observed in both nonalcoholic and alcoholic fatty liver, periportal steatosis was seen only in alcoholic fatty liver. Vascular markings were more prominent in alcoholic fatty liver, especially in those with fibrosis, compared with nonalcoholic fatty liver. Fat was not stained with ICG. Unstained red patches, observed after ICG administration in both nonalcoholic and alcoholic fatty liver, were thought to be due to congestion in the former and to lobular inflammation as well as congestion in the latter. Acinar markings were indistinct in the fatty liver with fibrosis but became clearer after ICG administration.

[Sex difference in alcoholic liver disease: with special reference to the severity of alcoholic hepatitis].

Purpose of this study was to elucidate the difference in severity of alcoholic liver diseases (ALD), especially of alcoholic hepatitis (AH) between female and male. We have experienced 15 female and 113 male patients with ALD laparoscopically and histologically proved during the past 10 years. In female patients, histological analysis revealed 8 cases of cirrhosis, 2 each cases of AH, fibrosis and chronic hepatitis, and 1 case of fatty liver. Occurrence of AH in female (13%) was significantly higher than male in which AH was seen in 3 cases (3%) (p less than 0.05). Duration of alcoholic abuse in female AH patients was shorter than male AH patients (5.5 +/- 0.5 years vs 24.0 +/- 2.9 years). Total alcohol consumed in female AH patients was less than male AH patients (256 +/- 52 kg vs 1560 +/- 703 kg). Abnormality in liver function tests including hepaplastin test, serum bilirubin, transaminases, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyltranspeptidase, immunoglobulins was outstanding in female patients compared with male patients. Histological findings such as hepatocellular ballooning, neutrophilic infiltration, fatty change and wiremesh fibrosis were intensive in female patients compared with male patients. In conclusion, there were much more severe ALD like AH or cirrhosis in female than male patients. In female AH patients duration of alcoholic abuse was shorter and total alcohol consumed was less than male AH patients. And it was suggested that female AH is clinically and pathologically getting severe compared with male AH.

Marked increase in serum alpha-fetoprotein level in cirrhosis: a case report.

A 56-yr-old Japanese man with chronic liver disease was admitted for evaluation of increased serum alpha-fetoprotein reaching levels as high as 7190 ng/ml. The presence of hepatocellular carcinoma was ruled out by computed tomography and hepatic angiography. Laparoscopy and liver biopsy sample showed active liver cirrhosis. alpha-Fetoprotein granules were positive in hepatocytes. The rise in serum alpha-fetoprotein level was transitory and returned to less than 100 ng/ml 4 wk later. It was suggested that regeneration after acute exacerbation of cirrhosis might have been closely related to the dramatic increase in alpha-fetoprotein production.

Severe jaundice in malignant lymphoma. Report of two autopsy cases.

Two autopsy cases of malignant lymphoma with marked hyperbilirubinemia (18.6 and 36.5 mg/dl at maximum) are presented. Histology revealed the portal area to be enlarged due to lymphoma cell infiltration and cholestasis in the hepatic lobules in both. Of 30 cases of malignant lymphoma treated in our department, hyperbilirubinemia was seen in 7 cases (23%) including these two cases (6.7%) which were severely jaundiced. The occurrence rate of jaundice in malignant lymphoma to all jaundiced diseases showing serum total bilirubin levels of more than 5 mg/dl was 0.7%.