Masaru Shimizu

Fulminant hepatitis B: Induction by hepatitis B virus mutants defective in the precore region and incapable of encoding E antigen

Clones of hepatitis B virus were propagated from 10 cases of fulminant hepatitis B after amplification by polymerase chain reaction and their nucleotide sequences of the precore region were determined. All 113 clones from 9 cases had a point mutation from guanine to adenine at nucleotide 83 in the precore region, which converted codon 28 for tryptophan (TGG) to a stop codon (TAG) and prohibited the synthesis and secretion of hepatitis B e antigen. Precore-region defects were not detected in any of 23 clones from the remaining 1 case. By contrast, precore-region defects were not found in any of 180 clones from 8 cases of acute hepatitis B without hepatic failure serving as controls. The source of infection was traceable in 3 cases. The same precore-region defect, along with the sequence identity of 435 nucleotides, was observed in clones from the case of a baby and his grandmother, who carried the virus and was implicated in the transmission, and also in clones from two pediatricians and the carrier patients they attended. These findings support the hypothesis that precore-defective mutants have stronger activity to induce fulminant hepatitis than nondefective viruses.

Posttransfusion Fulminant Hepatitis B Associated with Precore‐Defective HBV Mutants

Abstract. Fulminant hepatitis B developed in 8 recipients of blood units without detectable hepatitis B surface antigen on routine screening. All 124 hepatitis B virus (HBV) DNA clones propagated from their sera possessed defects in the precore region. A point mutation from guanine to adenine at nucleotide 83, converting codon 28 for tryptophan (TGG) to a stop codon (TAG), was the commonest, and it was found in all 113 clones from 7 cases. The remaining case displayed 1 clone with this point mutation and 10 clones with an insertion of 2 base pairs after nucleotide 26. Antibody to hepatitis B core antigen (anti‐HBc) was detected in a high titer in 1 of 10 pilot plasma samples of blood units transfused to this case. HBV DNA clones propagated from it exhibited the same precore‐region defects as those from the recipient. On the basis of these results HBV mutants, defective in the precore region, would appear to be responsible for posttransfusion fulminant hepatitis B, and the exclusion of blood units with high‐titered anti‐HBc would be efficacious in preventing it.

Impact of fresh-frozen plasma from male-only donors versus mixed-sex donors on postoperative respiratory function in surgical patients: a prospective case-controlled study

BACKGROUND: To reduce the risk of transfusion‐related acute lung injury (TRALI), plasma products are mainly made from male donors in some countries because of the lower possibility of alloimmunization; other countries are considering this policy. The advantage of male‐only fresh‐frozen plasma (FFP) should be examined in a prospective case‐control study.

GB Virus C and Hepatitis C Virus Infections in Hemodialysis Patients in Eight Japanese Centers

RNA of a putative non-A to E hepatitis virus, designated GB virus C (GBV-C), was detected in 40 (6.2%) of 645 hemodialysis patients, at a frequency significantly higher than in 3 (0.9%) of 336 blood donors in Japan (p < 0.001). A history of transfusion was more frequent (88 vs. 58%, p < 0.001), the duration of dialysis was longer (13.2 +/- 7.9 vs. 7.9 +/- 6.5 years, p < 0.001), and the detection of hepatitis C virus RNA was more often (38 vs. 18%, p < 0.01) in the 40 patients with GBV-C RNA than in the 605 patients without it. The prevalence of GBV-C RNA varied widely from 0 to 10% among the 8 dialysis centers. These results indicate that hemodialysis patients would be at increased risk of GBV-C transmitted by transfusions. The detection of GBV-C RNA in the 5 patients without a history of transfusion and a high prevalence restricted to certain dialysis centers would reflect nosocomial infection.

Selective absence of immunoglobulin A1 or A2 among blood donors and hospital patients

A hemagglutination inhibition assay was developed for the determination of immunoglobulin A1 and A2 (IgA1 and IgA2) with subclass‐specific rabbit antiserums. Among 93,020 apparently healthy blood donors, selective absence of IgA1 was found in six and that of IgA2 in 15, at a prevalence much higher than the absence of total IgA that was revealed by only one donor. Among 6800 hospital patients with various disorders, the absence of IgA1 was found in one with breast cancer and that of IgA2 in two with rheumatoid arthritis.

Clinical evaluation of repeat apheresis donors in Japan.

AbstractBackground and Objectives: To ascertain the safety of repeat apheresis donation, hematological and biochemical tests were performed on 511 donors with a donation rate of over 6 times per year for a period of 12–19 months. Materials and Methods: Repeat donors who had apheresis more than 6 times in the previous year were chosen. Data for the repeat donors at the start of the experiments were compared with those at the end of the end of the study. Blood samples were taken prior to donation. Serum protein, albumin, immunoglobulin G, A, and M, serum ferritin levels were determined by biochemical tests. Results: When compared to prospective donors of 400 ml, WBC, lymphocytes, and serum ferritin levels were lower in a roughly frequency‐dependent manner in female and male donor groups at the beginning of the study. All the data for the male group remained almost constant with increasing frequency of apheresis donation. However, in the female group, ferritin levels significantly decreased with over 21 donations. Conclusions: The present data showed that the serum ferritin level of the female donors decreased the most with increasing frequency of apheresis donation. The cumulative RBC left in the collecting chamber and for the laboratory test is discussed in relation to a possible cause of iron deficiency in frequent apheresis donors.

Standardization of Bromelin for Use in Routine One‐Stage Antibody Screening

Abstract. A simple standardization method for bromelin used in routine one‐stage antibody screening is described. Bromelin proteinase activity was assayed using casein as the substrate, and converted to units. The use of proteinase activity units for standardization of bromelin resolves differences between commercial preparations.

Effect of Donor Blood Screening for Anti-HCV Antibody by the Second-generation Passive Hemagglutination Test on the Incidence of Post-Transfusion Hepatitis

The aim of this study was to determine whether the second-generation anti-HCV antibody passive hemagglutination (PHA) test would offer more effective control of post-transfusion non-A, non-B hepatitis (NANBPTH). Firstly, the sensitivity and specificity of the first- and second-generation anti-HCV antibody tests were compared to HCV-RNA results by polymerase chain reaction (PCR) in 365 donor blood samples. Secondly, a prospective study to assess the effectiveness of second-generation PHA screening of 174 open-heart surgery patients was begun in May, 1992. PHA was positive in 98.6% of 138 donor samples with HCV-RNA, vs only 62.3% for enzyme-linked immunosorbent assay (ELISA). None of the open-heart patients seroconverted to HBV or HCV, although seven developed acute hepatitis. Screening with PHA resulted in a remarkable decrease in NANBPTH. However, there remain some risk factors for post-transfusion hepatitis to be clarified, perhaps involving a non-C hepatitis virus.

H2O2 Release from Filtration Leukapheresis-Procured Leukocytes

Abstract. Filtration leukapheresis‐procured leukocytes (FL‐leukocytes), which were collected by the elution of filtration columns with vigorous tapping, released a certain amount of H2O2, even in the absence of any phagocytic stimuli. Furthermore, FL‐leukocytes, eluted with either gentle or vigorous tapping, exhibited a marked release of H2O2 during phagocytosis. The myeloperoxidase (MPO) activity of FL‐leukocytes was lower than that of leukocytes collected by the dextran sedimentation method (DS‐leukocytes). The data suggest that the release of both H2O2 and MPO from FL‐leukocytes may be related to adverse transfusion reactions and abnormal post‐transfusion kinetics of FL‐leukocytes due to their toxic effects on living cells.

Autotransfusion Supported by Erythropoietin Therapy in Transurethral Resection of the Prostate

We investigated the collection and transfusion of autologous blood after treatment with EPO in 68 BPH patients (including 10 controls) who were scheduled to undergo TUR-P. All patients received oral and/or intravenous iron supplements. Assessments were made based on the preoperative increase in blood hemoglobin levels including autologous blood predonation (deltaHb). The deltaHb in patients undergoing collection of 600 ml of blood were as follows: control group: -0.36 +/- 0.57 g/dl; EPO group, 9 x 3000 units intravenously: 1.15 +/- 0.83 g/dl; EPO group, 6 x 6000 units intravenously: 0.79 +/- 0.80 g/dl; EPO group, 3 x 12,000 units subcutaneously: 1.47 +/- 0.62 g/dl. In patients undergoing collection of 800 ml of blood, the results were as follows: EPO group, 3 x 12,000 units subcutaneously: 1.80 +/- 0.69 g/dl; EPO group, 3 x 24,000 units subcutaneously: 2.03 +/- 0.77 g/dl. All EPO-treated patients successfully underwent surgery using their own blood, and none of them required homologous transfusion. The increase of Hb was greater in the patients treated with EPO than in controls, allowing safe preoperative blood collection even in elderly patients. In patients with relatively severe BPH, homologous transfusion could be avoided and surgery was performed safely.