CATALOGIC 301C model - validation and improvement.

In Europe, REACH legislation encourages the use of alternative in silico methods such as (Q)SAR models. According to the recent progress of Chemical Substances Control Law (CSCL) in Japan, (Q)SAR predictions are also utilized as supporting evidence for the assessment of bioaccumulation potential of chemicals along with read across. Currently, the effective use of read across and QSARs is examined for other hazards, including biodegradability. This paper describes the results of external validation and improvement of CATALOGIC 301C model based on more than 1000 tested new chemical substances of the publication schedule under CSCL. CATALOGIC 301C model meets all REACH requirements to be used for biodegradability assessment. The model formalism built on scientific understanding for the microbial degradation of chemicals has a well-defined and transparent applicability domain. The model predictions are adequate for the evaluation of the ready degradability of chemicals.

Increased incidence of bone metastases in hepatocellular carcinoma.

OBJECTIVES: Recently, we often encounter hepatocellular carcinoma patients with bone metastases. We therefore examined the changes in the incidence of bone metastases in hepatocellular carcinoma from 1978 to 1997 and tried to identify the characteristic clinical features. We also discuss the reasons for the increased incidence of bone metastasis in hepatocellular carcinoma. METHODS: A total of 673 patients with hepatocellular carcinoma during the period 1978-1997 were studied. Bone metastasis was screened by bone scintigraphy, and bone lesions were confirmed by plain radiography, computed tomography and/or magnetic resonance imaging. The serum levels of the C-terminal telopeptide of type 1 collagen, which represent osteoclastic bone resorption, were also measured. RESULTS: The incidence of bone metastasis during the decade 1988-1997 was significantly higher than that during the period 1978-1987. The median survival time of patients with hepatocellular carcinoma during 1988-1997 was also significantly longer than that during 1978-1987. Portal thrombus was found in about half of the patients with bone metastases. The most common site of bone metastases was the vertebra followed by the pelvis, rib and skull in that order. All bone lesions depicted by plain radiograph, computed tomography and/or magnetic resonance imaging were of the osteolytic type, and the serum levels of C-terminal telopeptide of type 1 collagen were significantly elevated in the patients with bone metastases. CONCLUSIONS: The increased incidence of bone metastasis in hepatocellular carcinoma in the decade 1988-1997 is first attributed to the prolonged survival rate of hepatocellular carcinoma patients due to recent progress in both the diagnosis and treatment of the disease. Dissemination of hepatocellular carcinoma cells to the vertebra through the portal vein-vertebral vein plexuses due to the presence of portal thrombus and/or portal hypertension may be related to a higher incidence of bone metastasis in hepatocellular carcinoma. Both an early diagnosis and timely treatment of bone metastases are thus called for in the follow-up of hepatocellular carcinoma patients.

MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation.

MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase that, in addition to regulating the c-Jun NH(2)-terminal kinase (JNK) pathway, is involved in the control of cell motility. MEKK1(-/-) mice are defective in eyelid closure, a TGFalpha-directed process involving the migration of epithelial cells. MEKK1 expression in epithelial cells stimulates lamellipodia formation, a process required for cell movement. In addition, mouse embryo fibroblasts derived from MEKK1(-/-) mice are inhibited in their migration relative to MEKK1(+/+) fibroblasts. MEKK1 is required for JNK but not NF-kappaB activation in response to virus infection, microtubule disruption, and stimulation of embryonic stem cells with lysophosphatidic acid. MEKK1 is not required for TNFalpha or IL-1 regulation of JNK or NF-kappaB activation in macrophages or fibroblasts. Thus, MEKK1 senses microtubule integrity, contributes to the regulation of fibroblast and epithelial cell migration, and is required for activation of JNK but not NF-kappaB in response to selected stress stimuli.

Heat-induced drug resistance is associated with increased expression of Bcl-2 in HL60.

HL60 cells underwent apoptosis with heat treatment, i.e. exposure to 42 degrees C for 120 minutes. Cells exposed to the same temperature for 30 minutes became resistant to subsequent, otherwise lethal, heat shock. These thermotolerant cells also acquired resistance to anti-cancer drugs including daunorubicin and VP16. We found that mild heat shock upregulates not only HSP70 but also BCL-2, though BCL-2 has not previously been recognized as a heat-inducible protein. Expression of BCL-2 closely paralleled resistance to subsequent exposure to anticancer drugs. The present results suggest that BCL-2 may play a role in heat-induced drug resistance.

Estimation of bacterial contamination in ultrapure water: application of the anti-DNA antibody.

We constructed and established a hybridoma cell line that produces immunoglobulin G-type anti-DNA antibody. By using this antibody, we could successfully detect a single bacterial cell in ultrapure water (UPW). The detection system is composed of a membrane-supported western blotting-type immunoassay and a two-dimensional photon analyzer with high resolution. It can detect and count every bacterial cell in a wide field of view on a trapping filter i.e., a circle with an 18-mm diameter. This means 10 fg (10(-14) g) of bacterial DNA can be detected in the field. This system could be a useful tool for evaluating the number of bacteria contained by UPW and water used for medical purposes.

[Readmission among discharged psychiatric patients and it's correlates].

OBJECTIVE: This study investigated the incidence of readmission among discharged psychiatric patients and examined factors predicting early readmission. METHODS: A cohort of 343 patients, who had been hospitalized involuntarily to mental hospitals for medical care and custody, and who were discharged between April 1991 and September 1993, in two areas served by Fukuoka Prefectural Yamato Health Center (n = 163) and Tagawa Health Center (n = 180) were followed up until November 1994. RESULTS: The readmission rates within 6 months of discharge in Yamato Health Center and Tagawa Health Center were 17% and 22%, and within 1 year were 30% and 31% respectively. From Cox's proportional hazards model, alcohol/drug abuse, many of previous admission, long length of recent hospitalization, payment of medical care cost from public assistance, complication of physical disorders, living without a person responsible for custody after discharge, no request of health center's service by the hospital and discharge from a large-scale mental hospital were significantly related to increased risk of readmission. Not a few patients could not be followed up completely because of early drop-out of treatment. The drop-out rates within 1 month of discharge in Yamato Health Center and Tagawa Health Center were 10% and 26%, and within 1 year were 15% and 27% respectively. CONCLUSIONS: The rates of readmission and drop-out of treatment among discharged psychiatric patients were considerably high. This study clarified that rapid establishment of a mental health system supporting the mentally disabled in a community is an urgent need in Japan.

Donor leukocyte transfusions and discontinuation of immunosuppressants to achieve an initial remission after allogeneic bone marrow transplantation in a patient with primary refractory acute leukemia.

We present a female patient who received an allogeneic bone marrow transplantation for primary refractory Philadelphia-positive acute biphenotypic leukemia. Since leukemic blasts were persistently present in peripheral blood and bone marrow, in spite of the evidence for engraftment of male donor hematopoiesis, we performed donor leukocyte transfusions and discontinued immunosuppression. An initial complete remission was obtained 15 weeks after allogeneic bone marrow transplantation, and lasted for 24 weeks. We concluded that the prominent mechanism for the eradication of the refractory leukemic clone in the patient was the graft-versus-leukemia effect.

Ataxia-telangiectasia with renal cell carcinoma and hepatoma.

This paper reports the occurrence of renal cell carcinoma, hepatoma and malignant hepatic mixed tumor in a 22-year-old male with ataxia-telangiectasia (AT). Incidence of various malignant neoplasms is high in the patients with AT. The majority of these are lymphoreticular tumors and leukemia, and epithelial tumors are rare. This report is the first case with renal cell carcinoma and the second with hepatoma. The reason for a low incidence of epithelial tumors in AT is still obscure. It is possible that as the result of abnormal aging the tumors expected in the aged will occur in longer survivors with AT.