Head-to-head comparison between two screening systems for HBsAG, anti-HBc, anti-HCV and HIV combination immunoassays in an international, multicentre evaluation study.

BACKGROUND: Mandatory screening of blood donations for hepatitis B and hepatitis C viruses and human immunodeficiency viruses 1 and 2 requires assays with exceptional sensitivity and specificity. This study reports the results from a direct head-to-head comparison of the Elecsys HBsAG II, Elecsys Anti-HBc, Elecsys Anti-HCV II and Elecsys HIV combi PT immunoassays with the respective ABBOTT PRISM/Architect instrument immunoassays in a multicentre blood bank evaluation study. STUDY DESIGN AND METHODS: Assay validation was performed in the blood screening laboratories of four blood bank centres in Austria, Germany, Spain and Thailand, where both first-time donor samples (approximately 6000 donors) and repeat donor samples (approximately 14,000 donors) were screened. RESULTS: Of all screened donor samples, 93 (0.46%) were confirmed to be positive using assays from both manufacturers. The specificity of all immunoassays was >99.5% and was comparable between first-time and multiple-time donors. A direct comparison between the assays from Roche and ABBOTT according to Bland and Altman analysis demonstrated equivalent quality. CONCLUSIONS: These results suggest that the Elecsys immunoassays for HBV, HCV and HIV infection, with a comparative sensitivity of 100% and a specificity exceeding the common technical specification threshold of >99.5%, meet the stringent performance criteria stipulated for blood donor screening for these infectious agents. Significant differences in the specificity between first-time and repeat donors were not detectable.

Genetic characterization and genotyping of hepatitis B virus (HBV) isolates from donors with an occult HBV infection.

BACKGROUND AND OBJECTIVES: Screening of Thai blood donors has resulted in the detection of donors with an occult HBV infection (OBI), where HBsAg is undetectable, but hepatitis B virus (HBV) DNA is present in serum in low concentrations. This study was designed to determine whether the occurrence of OBI in donors was linked to the HBV genotype and possibly to mutations in the surface (S) and core (C) gene regions. MATERIALS AND METHODS: Mutations in the S and C gene regions in 48 Thai donors with OBI were mapped by sequencing. Genotyping was determined with the INNO-LiPA test and by phylogenetic analysis of sequences from the S and C genes. RESULTS: The majority of OBI samples were genotype C (81·3%) with 6·3% of samples being genotype B. In addition, two genotype I isolates were identified. Mutations in the S region (100%) were found especially in loop 1 of the major hydrophilic loop (MHL) at positions I110L, T114S, T126I and S113T, whereas mutations in the C region (65%) were within the basal core promoter region (position A1762T/G1764A) and precore region (position G1896A). CONCLUSION: The majority of OBI samples were HBV genotype C, although genotype I, which is newly emerging in Thailand, was also detected. The study demonstrated that OBI was probably not associated with a particular HBV genotype or with certain mutations in the S and C gene regions. However, mutations in the C gene region which could potentially impair viral replication and HBsAg production and potentially lead to OBI were identified.

Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999.

We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0+/-1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies.

Four-dimensional quantitative analysis of the gait of mutant mice using coarse-grained motion capture.

To analyze an abnormal gait pattern in mutant mice (Hugger), we conducted coarse-grained motion capture. Using a simple retroreflective marker-based approach, we could detect high-resolution mutant-specific gait patterns. The phenotypic gait patterns are caused by extreme vertical motion of limbs, revealing inefficient motor functions. To elucidate the inefficiency, we developed a musculoskeletal computer model of the mouse hindlimb based on X-ray CT data. By integrating motion data with the model, we determined mutant-specific musculotendon lengths, suggesting that three major muscles were involved in the abnormal gait. This approach worked well on laboratory mice, which were putatively too small to be motion capture subjects. Motion capture technology was originally developed for human study, and our approach may help fill neuroscience gaps between mouse and human behavioral phenotypes.

Development of MBR with reduced operational and maintenance costs.

To reduce MBR O&M costs, a new MBR process that conducts efficient simultaneous biological nitrogen and phosphorus removal (BNR) was developed. In the development of this process, various approaches were taken, including reduction of power demand, chemical consumption and sludge disposal costs. To address power demand reductions, air supply requirements for membrane cleaning were reduced. The process adopted an improved membrane that requires less air for cleaning than conventional membranes. It also introduced cyclic aeration, which alternately supplies washing air to the two series of membrane units. Adoption of biological phosphorus removal eliminated chemical costs for phosphorus removal and contributed to the reduction of sludge disposal costs. By combining these technologies, compared to conventional MBR processes, an approximately 27% reduction in O&M costs was achieved.

Evaluation of MBR effluent characteristics for reuse purposes.

One of the advantages of MBR is its excellent effluent quality, which is suitable for a wide range of reuse purposes. We investigated the characteristics of MBR effluent and evaluated them based on the Japanese guideline for the reuse of treated wastewater. As the result, MBR effluent showed qualitative coaracteristics that satisfy the requirement except chromaticity for recreational purpose. Further treatment, such as by oxone or activated carbon, will be required to remove the remaining color. MBR shows high removal efficiency of bacteria and other hazardous microorganisms such as Cryptosporidium. We investigated the removal efficiency of virus by MBR using coliphage as an alternative index. The results showed that high removal efficiency for coliphage could be obtained by MBR. The removal mechanism appears to be that coliphage are attached to the activated sludge and thus rejected by the membrane together with activated sludge particles. With regard to the endocrine disrupters, no significant differences were observed between MBR and CAS in the removal of main endocrine disrupters.

DNA sequence and comparative analysis of chimpanzee chromosome 22.

Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized.

[Disseminated bone marrow metastases from gastric cancer: detection and monitoring the effectiveness of chemotherapy by bone marrow scintigraphy].

Disseminated bone marrow metastasis of cancer is a critical condition, frequently complicated by disseminated intravascular coagulation (DIC). A 32-year-old man with gastric cancer was diagnosed as having disseminated bone marrow metastases. Bone scintigraphy demonstrated many abnormal radionuclide accumulations in the whole body. Bone marrow aspiration revealed cancer cells. Bone marrow scintigraphy with 111In-Cl3 demonstrated central marrow failure and peripheral expansion. The remission of DIC was observed after sequential methotrexate and 5-FU therapy, then uptake of radionuclide in the central bone marrow was remarkably improved by bone marrow scan. After thirteen anti-cancer chemotherapies, recurrence of DIC was suspected because of the reduction of blood platelet count. Nevertheless, repeated bone marrow scan still demonstrated the central bone marrow clearly. The patient discharged from our hospital without the recurrence of DIC. We considered bone marrow scintigraphy is useful in the detection of disseminated bone marrow metastases of cancer and monitoring the effectiveness of chemotherapy.

[Neoadjuvant chemotherapy with cisplatin and CPT-11 for advanced cervical cancer].

Neoadjuvant chemotherapy (NAC) is currently used for the treatment of advanced cervical cancer by many institutions. We investigated the value of NAC followed by radical surgery and/or radiotherapy for patients with locally advanced cervical cancer. Sixteen patients with stage Ib2-IIIb cervical cancer were enrolled in this study. CPT-11 (60 mg/m2) in 500 m/5% glucose was given intravenously on Days 1, 8, and 15, before cisplatin (60 mg/m2) in 500 ml normal saline. The treatment was repeated every 4 weeks for 2 or 3 cycles. All patients were evaluable for response and toxicity. Two achieved a clinical complete response (CR), 11 had a partial response (PR), 2 had no change (NC) and 1 had progressive disease (PD), for an overall response of 81.3%. Neutropenia was observed in 100% (> grade 3: 70.6%) and diarrhea was recorded in 55.9% (> grade 3: 5.9%). The combination of CPT-11 and cisplatin in locally advanced cervical cancer is thus an active regimen with a manageable toxicity as a neoadjuvant chemotherapy.

Phylogenetic relationship of muscle tissues deduced from superimposition of gene trees.

Muscle tissues can be divided into six classes; smooth, fast skeletal, slow skeletal and cardiac muscle tissues for vertebrates, and striated and smooth muscle tissues for invertebrates. We reconstructed phylogenetic trees of six protein genes that are expressed in muscle tissues and, using a newly developed program, inferred the phylogeny of muscle tissues by superimposition of five of those gene trees. The proteins used are troponin C, myosin essential light chain, myosin regulatory light chain, myosin heavy chain, actin, and muscle regulatory factor (MRF) families. Our results suggest that the emergence of skeletal-cardiac muscle type tissues preceded the vertebrate/arthropod divergence (ca. 700 MYA), while vertebrate smooth muscle seemed to evolve independent of other muscles. In addition, skeletal muscle is not monophyletic, but cardiac and slow skeletal muscles make a cluster. Furthermore, arthropod striated muscle, urochordate smooth muscle, and vertebrate muscles except for smooth muscle share a common ancestor. On the other hand, arthropod nonmuscle and vertebrate smooth muscle and nonmuscle share a common ancestor.

Treatment of Fetal Premature Ventricular Contractions by Administering Propranolol Hydrochloride Orally to the Mother.

> Frequent fetal premature ventricular contractions were diagnosed at 39 weeks of gestation. To avoid unnecessary cesarean section, the mother was administered propranolol hydrochloride orally. The tococardiography became feasible and permitted us to evaluate fetal well-being. The patient successfully delivered transvaginally a male infant at 40 weeks of gestation.

[An operative case of bilateral peripheral pulmonary arterial aneurysms].

An operative case of bilateral peripheral pulmonary arterial aneurysms is described. Nine cases of bilateral peripheral pulmonary arterial aneurysms reported in Japan are reviewed. The patient was a 26-year-old woman complaining of massive hemoptysis. Her chest X-ray showed coin lesions in the bilateral hilus region. After admission, body CT and pulmonary arteriography revealed saccular dilatation of the bilateral peripheral pulmonary artery. We diagnosed as bilateral peripheral pulmonary arterial aneurysms. Bronchoscopic examination revealed bleeding from the left lower lobe bronchus. She underwent left lower lobectomy. Histological examination of the resected specimen demonstrated a marked destruction of the wall of the aneurysm. This patient died of recurrence of hemoptysis from bilateral lung on the 42nd postoperative day.

[Extramedullary plasmacytoma with multiple metastasis following a maxillary plasmacytoma].

A 67-year old man noticed swelling of left maxillary in October 1992. Surgical biopsy of the left maxillary tumor revealed the plasmacytoma at the department of oral surgery. The Tumor disappeared after radiation therapy. He was admitted with dizziness and tarry stool in June 1994. We found left cervical and abdominal paraaortic lymph node swellings by the computer tomography. He died inspite of chemotherapy in December. Autopsy showed that plasma cells diffusely and nodularly invased in all alimentary tract with multiple ulcerations. Invasion was also observed in the liver, lungs, thyroid, heart, kidneys, and adrenals. The plasma cells in the liver showed IgG kappa type by tissue immunostain. Diffuse invasion of extramedullary plasmacytoma is very rare in alimentary tract and many other organs. This case may be value to delineate the nature of this disease.

[Studies of transrectal prostatic ultrasonography on patients with male infertility].

The diagnostic significance of transrectal prostatic ultrasonography for chronic prostatitis and varicocele was evaluated in 380 male infertility patients. Of 20 patients with pyospermia, thought to be mainly caused by chronic prostatitis, 10.0 percent showed heterogeneous echo pattern of the prostate, while 25.0 percent showed capsular irregularity. Since 285 patients with non-infected semen showed similar sonographic findings, it is concluded that prostatic ultrasonography has little value in the diagnosis of chronic prostatitis in infertile patients. Enlarged periprostatic echo-free zone, thought to coincide with the dilatation of the Santrini's plexus, was found in 42.9 and 42.7 percent of patients with chronic prostatitis and varicocele, respectively, in contrast to 34.0 percent of patients without either diseases. Twelve percent of patients with varicocele showed highly enlarged echo-free zone, which was significantly more frequent compared to 5.0 percent in normal patients. Moreover, follow up of 4 patients with varicocele pre- and post-operatively found 2 of them to show a great improvement in the enlargement of the zone. These results suggest that varicocele may cause the dilation of the Santrini's plexus through a venous anastomosis in some patients and transrectal ultrasonography may be a useful tool in detecting small varicoceles in such patients.

[Postoperative disturbance of consciousness due to tumor emboli of the orifice of pulmonary artery].

We reported a case of an abrupt hypotension and hypoxemia which lasted more than 60 min due to emboli of tumor at the orifice of the pulmonary artery during operation. Although the emboli were removed under the cardiopulmonary bypass (CPB) and later the patient regained good respiratory and hemodynamic conditions, he had a disturbance of consciousness after the operation. We began oxygen hyperbaric therapy (OHP) from the 6th postoperative day under spontaneous ventilation. His consciousness improved quickly after the beginning of OHP. We conclude that OHP and CPB might be useful to treat the postoperative disturbance of consciousness due to hypotension and hypoxemia during operation.

[A case of metastatic urinary bladder tumor from colon carcinoma].

A 62-year-old female patient underwent an operation for a brain tumor. The pathological diagnosis of the resected specimen was metastatic adenocarcinoma with signet-ring cells. The primary lesion was found in the ascending colon. In addition, a non-papillary and pedunculated tumor was found on the right wall of the bladder on cystoscopy. Biopsy of the bladder tumor showed adenocarcinoma with signet-ring cells, which was the same as the histologies of the colon and the brain tumors. Under the diagnosis of metastatic bladder tumor, transurethral resection of the tumor was performed. This is the first case of metastatic bladder carcinoma from the colon reported in Japan.