Severe hypogammaglobulinemia associated with hepatic vein stenosis causes cytomegalovirus infection after living-related liver transplantation.

Hepatic vein stenosis is a vascular complication that can lead to graft loss after liver transplantation. Although ascites frequently occurs as a symptom of hepatic vein stenosis, the development of severe hypogammaglobulinemia associated with hepatic vein stenosis has not been reported in the literature. An 8-year-old boy underwent living-related liver transplantation (LRLT) because of Wilson disease with chronic hepatic failure. Because de novo autoimmune hepatitis was diagnosed 1 year after LRLT, azathioprine, and prednisolone were added to the baseline immunosuppression of tacrolimus. The patient developed ascites with severe hypogammaglobulinemia (immunoglobulin G [IgG], 288 mg/dL) 2 years after LRLT. Ultrasonography and angiography disclosed stenosis of the hepatic vein. The ascites completely resolved after percutaneous balloon angioplasty. Despite serum IgG trough levels of >500 mg/dL maintained by the addition of immunoglobulin, cytomegalovirus reactivation and sepsis occurred. Serum IgG levels should be monitored to prevent opportunistic infections when hepatic vein stenosis is diagnosed after LRLT.

Sequence analysis of hepatitis B virus genomes from an infant with acute severe hepatitis and a hepatitis B e antigen-positive carrier mother.

It is well known that fulminant hepatitis B can occur in infants born to hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) carrier mothers, whereas fulminant hepatitis and severe hepatitis are uncommon in infants born to HBeAg-positive mothers. We have encountered an infant with severe acute hepatitis B born to a HBeAg-positive mother. The aim of this study was to determine whether HBV variants contribute to the pathogenesis of fulminant hepatitis and severe hepatitis in an infant born to an HBeAg-positive mother. The nucleotide sequence of HBV genomes from the infant and his HBeAg-positive carrier mother was analyzed. All HBV isolated from the infant and his mother were subtype adr. The sequences of the cloned HBV genomes, each including a part of the X and precore/core regions, isolated from the infant were almost identical (homology of 99.1-99.9%) to those from his mother. There was no mutation in any of the 17 clones examined at nucleotides 1762 and 1764 in the core promoter, which is reported to be associated with fulminant hepatitis. A point mutation at nucleotide 1758 in the second AT-rich region of the basic core promoter was present in all clones. None of the clones had a point mutation at nucleotide 1896 of the precore region. In this study, no specific HBV variants contributing to the development of neonatal severe hepatitis were found. There is a possibility that host factors rather than viral factors play an important role in some cases of severe neonatal hepatitis B.

Long-term outcome of chronic hepatitis B in adolescents or young adults in follow-up from childhood.

BACKGROUND: It has not yet been defined whether children with chronic hepatitis B are likely to develop severe liver disease in the future. The purpose of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood. METHOD: Fifty-two children in the age range of 0 to 15 years who were positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months were enrolled in this study. In the majority of the 52 children, hepatitis B virus infection was acquired by perinatal transmission. All 52 showed abnormal liver function test findings for more than 6 months before enrollment, and the subjects were followed up longitudinally for 3 to 22 years (mean, 11 years). They are now more than 15 years of age (15-27 years old). RESULTS: During the follow-up period, 26 (50%) children had spontaneous seroconversion to anti-hepatitis B e. Serum levels of alanine aminotransferase normalized in these 26 children. In one child of these children, hepatocellular carcinoma developed at the age of 21 years, 16 years after seroconversion, although his liver function profiles remained normal. The other 26 children remained hepatitis B e antigen positive, most with unchanged biochemical features. Sixteen (62%) children among these 26 children were treated with interferon-alpha. Eleven (69%) children had seroconversion to anti-hepatitis B e within the first year after the cessation of therapy. Hepatocellular carcinoma developed in 1 of these 11 children at the age of 16 years, 6 years after interferon therapy. Thus, hepatocellular carcinoma developed in two children in an anti-hepatitis B e positive phase. CONCLUSION: All children carrying hepatitis B surface antigen should be observed carefully to monitor the possible development of hepatocellular carcinoma, especially in the antihepatitis B e-positive phase after spontaneous seroconversion or even after interferon treatment.

Severe late acute allograft rejection in a child after living-related auxiliary partial orthotopic liver transplantation for ornithine transcarbamylase deficiency.

Auxiliary liver transplantation (ALT) is known to correct liver-based metabolic disorders. However, it remains unclear whether the presence of a native liver influences the long-term prognosis of ALT for metabolic diseases. We reported on a 4-yr-old girl who had undergone living-related auxiliary partial orthotopic liver transplantation (APOLT) for ornithine transcarbamylase deficiency and experienced severe late acute rejection 18 months after liver transplantation, during weaning of immunosuppressive agents. Results of histological analysis of the graft indicated very severe acute rejection (rejection activity index, 9/9), and computed tomography revealed graft liver atrophy. These observations suggest the possibility that severe rejection might occur in APOLT, especially during weaning of immunosuppression.

GBV-C/HGV infection in children with chronic hepatitis C.

The role of GB virus-C/hepatitis G virus (GBV-C/HGV), a recently identified member of the Flaviviridae family, in children with liver disease is not well understood. The aims of this study were to evaluate the prevalence of GBV-C/HGV and to clarify its pathogenic role in young patients with chronic hepatitis C. Sixty-four Japanese children and adolescents with chronic hepatitis C virus (HCV) infection, with a mean age of 9.8 years, were evaluated retrospectively. Twenty-one (32.8%) of the 64 patients were positive for serum GBV-C/HGV RNA. Only 1 (1.6%) of the 64 patients was positive for antibody against the envelope protein E2 of GBV-C/HGV (anti-E2) and GBV-C/HGV. None of them was positive for anti-E2 alone. There was no significant difference in clinical, virological, or histological characteristics between GBV-C/HGV-positive and GBV-C/HGV-negative patients, except for underlying malignant disease. There was no evidence that GBV-C/HGV might affect the response of HCV to interferon therapy in young patients with chronic hepatitis C. The prevalence of GBV-C/HGV infection in young patients with chronic hepatitis C is similar to that in adult patients with chronic hepatitis C, but E2-seroconversion is observed infrequently. Underlying malignant disease is a risk factor for GBV-C/HGV viremia. GBV-C/HGV does not seem to affect the clinical course of young patients with chronic hepatitis C.

Hepatitis B precore mutant in children with chronic hepatitis B virus infection.

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.

Transferability of results obtained for sodium, potassium and chloride ions with different analysers.

In this study we have assessed transferability in seven different analysers commonly used in clinical chemistry laboratories to measure sodium, potassium and chloride ions. The inaccuracy and linearity of the techniques were satisfactory in most cases, and therefore all the equipment may be used in both pathological and normal ranges of the electrolytes evaluated. In most cases it was possible to correct the inaccuracy. The equipment which gave the best performance when analysing the three ions assessed after considering the Process Capability Index (CPI) and Performance Index (PI) was Nova-5. According to Hyltoft-Petersen's criteria, the results obtained for the three ions with the different analysers cannot be used indiscriminately, apart from potassium. However, after comparison of the results obtained by indirect potentiometry with those obtained by other techniques, we can conclude that the transferability of results is possible in almost every case, as standard deviation from regression (Sy,x) was lower than the permissible analytical error.

[Preparation and characterization of monoclonal antibody to gamma seminoprotein].

Gamma seminoprotein (gamma Sm), a glycoprotein isolated from human seminal plasma with a molecular weight of 29,000 and possibly a serine protease, has been demonstrated to be one of the prostate organ-specific antigens. We established a murine monoclonal antibody (MoAb) to gamma-Sm in order to prove the presence and localization of this protein in the prostate. The hybrid clones were obtained by fusing mouse SP2/O-Ag-14 myeloma cells with splenocytes from Balb/c mouse immunized with the major fractions of gamma-Sm. The enzyme-linked immunosorbent assay was done for antibody screening. After cloning twice in soft agarose, the stable clone, termed 43-21-1-1, was finally chosen. This MoAb, IgG1(kappa), recognized gamma-Sm specifically, which was verified by an immunoblotting assay. The specificity of the MoAb was further evaluated by immunohistochemical study by the avidin biotin complex method. Periodate-lysine-paraformaldehyde-fixed surgical specimens, including the prostate associated with fibromuscular hyperplasia, seminal vesicles, bladder, testis and epididymis, were examined. Formaldehyde (10%)-fixed surgical specimens from patients with adenocarcinoma of the prostate and primary transitional cell carcinoma arising from the periurethral prostatic ducts were also examined. Positive reactions of gamma-Sm were recognized only in the cytoplasm of prostatic glandular epithelial cells and along the luminal surface. Fibrous and muscular tissues always given negative staining. Neither nonprostatic tissues nor transitional cell carcinoma of the prostate were stained positively for gamma-Sm. These results show that this MoAb (43-21-1-1) is quite specific to gamma-Sm and may be useful for the immunohistochemical study with prostatic tissue.

Preparation of monoclonal antibodies to glutathione S-transferase-pi and application to immunohistochemical study.

Glutathione S-transferase (GST) EC 2.5.2.18) catalyzes conjugation of reduced glutathione with hydrophobic substrates, such as S-epoxide active molecules. It participates in glutathione metabolism and the gamma-glutamyl cycle, playing an important role in detoxification and biosynthesis of many compounds. It is also known as a marker of pre-neoplasia in chemical hepatocarcinogenesis. Isoelectric focusing studies have revealed that this enzyme is composed of several isozymes, one of which, an acidic form of GST called GST-pi, has been extracted from human placenta. In this study, we prepared monoclonal antibodies (MAb) against human GST-pi from placenta. Specificity was confirmed by immunoblots of GST-pi after polyacrylamide gel electrophoresis and inhibition testing of enzyme activity by the antibody. The subclass of the antibody was IgG1 and the light chain was kappa. In light microscopic immunohistochemical studies of human placenta using the MAb, GST-pi was localized diffusely in the cytoplasm and along the apical cell membranes of syncytial cells in villi and in the cytoplasm of cytotrophoblastic cells in the basal plate. The MAb we prepared may also be useful for analyzing the enzyme's function in detoxification and biosynthesis of many compounds, as well as for oncological studies, such as diagnosis of malignant disease and localization of oncofetal proteins in malignant tissues.

Effect of graded coronary constriction on the flow reserve in regional myocardium in dog.

Effects of coronary constriction on the flow reserve of regional myocardium were studied in the anesthetized open-chest dogs. Regional myocardial blood flow (RMBF) was continuously measured using heated crossthermocouple method. Left circumflex coronary artery (LCX) was constricted gradually with a screw type constrictor. The coronary constriction decreased subendocardial myocardial blood flow, while subepicardial myocardial blood flow was not affected until reactive hyperemia in LCX nearly disappeared. Recovery and arrival to peak flow rate of RMBF following the release of 15-second's occlusion of LCX were progressively delayed with an increase in the constriction, especially in the subendocardial myocardium. Repayment of flow debt, however, was remained relatively well since the duration of reactive hyperemia in RMBF was prolonged by an increment of the constriction. From these findings, it might be concluded that in the heart with coronary stenosis recovery from ischemia was caused by prolonged duration of reactive hyperemia, and is suggested that the time required for recovery from ischemia or ischemic abnormalities after the cessation of stress might be an important marker for the severity of coronary insufficiency.