Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

874 records · Page 49Linked to original sources

PubMedDate not supplied

High-sensitivity antitumor drug sensitivity testing.

For antitumor drug sensitivity testing we have been performing the succinic dehydrogenase inhibition test using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). A new tetrazolium salt 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenyl-amino) carbonyl]-2H-tetrazolium hydroxide (XTT) has been synthesized recently, and we have been conducting basic studies using it. We were able to obtain a high degree of sensitivity by adding phenazine methosulfate as a promoter in this assay. In these assays, there was a positive correlation between absorbance and cell count and XTT assay was more sensitive than MTT assay. In XTT assay, the production of formazan increases with reaction time over a protracted period of time, we assessed the possibility of performing assays with fewer cells than MTT was used. The results using cancer cell lines showed that when reacted for a longer time (6 h), it was possible to perform adequate assays using this method with 5,000 cells per well, and it will be useful when the amount of biopsy specimen is limited. We also evaluated the inhibition index of each of the drugs, comparing it with the MTT assay.

Cell Count↗

PubMedDate not supplied

Loss of the tumor suppressor p53 gene at the liver cirrhosis stage in Japanese patients with hepatocellular carcinoma.

The incidence of p53 gene aberrations is reported to be about 20-50% in hepatocellular carcinomas (HCCs). In most cases, HCC is clinically preceded by liver cirrhosis, but the genetic changes in cirrhosis are not known well. Therefore, we studied the loss of heterozygosity (LOH) of the p53 gene in cirrhotic and neoplastic foci in the livers of patients with HCC. To assess the relationship between the LOH status of the p53 gene in the liver cirrhosis stage and that in HCC, we analyzed the samples microdissected from paraffin-embedded tissues using the polymerase-chain-reaction-based assay. We studied 18 patients with HCC. Fourteen of the 18 cases showed constitutional heterozygosity for the microsatellite markers. In 8 (57%) of the 14 informative cases, LOH was detected in primary HCCs. Among these 8 doubly informative (informative and LOH positive in primary HCC) cases, 5 cases (63%) showed LOH in liver cirrhosis lesions. The pattern of p53 allelic loss in the cirrhotic foci was identical with that in the corresponding tumor. The remaining 6 cases without LOH of the p53 gene in HCC showed on p53 loss in any cirrhotic foci. LOH of the p53 gene may occur before the development of HCC.

Aged↗

PubMedDate not supplied

Corticosteroid-induced psychotic and mood disorders: diagnosis defined by DSM-IV and clinical pictures.

The authors investigated long-term outcome and treatment strategy of corticosteroid-induced psychotic and mood disorders as defined by DSM-IV. Review of medical records of 2,069 referral patients revealed 18 applicable patients. Their clinical characteristics, longitudinal courses, and treatments were studied. The authors identified 15 patients with mood disorder and 3 patients with psychotic disorder. Increasing doses or resumption of corticosteroids had the strongest influence on the psychiatric course. These two corticosteroid-induced psychiatric disorders may have different pathophysiological substrates closely related to patient vulnerability. Effective psychopharmacological treatment options were indicated with consideration being given to the underlying diseases.

Adult↗

PubMedDate not supplied

Transcranial Doppler of a paradoxical brain embolism associated with a pulmonary arteriovenous fistula.

We herein report the case of a patient who had paradoxical brain embolism owing to a pulmonary arteriovenous fistula (PAVF) who was diagnosed as having a right-to-left shunt by transcranial Doppler (TCD) with saline contrast medium. TCD with saline contrast medium failed to detect any high-intensity transient signals immediately after catheter embolization of the PAVF. Thus, TCD with saline contrast medium was useful for identifying the presence of a right-to-left shunt and for confirming that the shunt had been obliterated after endovascular treatment.

Arteriovenous Fistula↗

PubMedDate not supplied

Cerebellar glioblastoma genetically defined as a secondary one.

We report here the case of a 29-year-old woman with cerebellar glioblastma. In the present case, tumor lesions were observed in each cerebellar hemisphere. The left-side lesion was diagnosed as glioblastoma, and the right-side lesion as malignant astrocytoma by histopathology. Immunohistochemistry revealed that the tumor cells of the left-side lesion was positive for p53, whereas epidermal growth factor receptors (EGFR) were negative in tumor cells from both sides. Genetic alterations were investigated using a genome DNA microarray (GenoSensor Array 300), which has led us to define this tumor as a secondary glioblastoma. The clinical presentation and genetic findings of this relatively rare entity are discussed.

Adult↗

PubMedDate not supplied

Application of anti-sialyl Lea monoclonal antibody, KM231, for immunotherapy of cancer.

A mouse monoclonal antibody (MoAb), KM231 raised against human gastric cancer was found to recognize sialyl Lea -epitope expressed on glycoprotein and glycolipid with high affinity. KM231 reacted with many human gastrointestinal cancer tissues and could detect the antigen shed in sera of cancer patients. The present study was designed to evaluate competence of KM231 for immunotherapy of cancer. We first confirmed that KM231 could probe the cancer cells in vivo by injecting biotinylated KM231 into nude mice bearing human colorectal carcinoma cell, SW1116. Light- and electron-microscopic examination showed that the MoAb was localized in the tumor tissues and bound to the plasma membrane and cytoplasmic endosomes. Imaging studies with 125I-labeled KM231 revealed specific localization of the antibody in SW1116 tumors transplanted into nude mice. From Scatchard analysis of KM231 binding, the number of KM231 molecules bound to per SW1116 cell was calculated approximately 1.9 x 10(6) and the association constant was 1.3 x 10(8) liter/mol. We made KM231-ricin A chain immunotoxin for evaluating the tumoricidal effect of KM231. The immunotoxin exerted strong cytotoxicity toward sialyl Lea-expressing tumor cells specifically in vitro, but not toward sialyl Lea non-expressing cells. The in vivo tumoricidal effect of the immunotoxin was examined on ascites and subcutaneous xenograft tumors in nude mice. Three intraperitoneal injections of the immunotoxin (1.6 x 10(-6) mol) into nude mice bearing SW1116 ascites tumor resulted in extension of survival by 204% compared with controls. Further, repeated intraperitoneal administration of the immunotoxin (1.4 - 2 x 10(-6) mol) significantly inhibited the growth of established subcutaneous tumor (ratio of tumor inhibition = 0.7 - 0.54). These results indicated that KM231 has the ability to probe sialyl Lea-expressing tumor cells in vivo with high efficiency and to become tumoricidal drug when it conjugated with cytotoxic reagents like ricin A chain.

Animals↗

PubMedDate not supplied

Social and legal factors related to drug abuse in the United States and Japan.

This article is an overview of social and legal differences in the United States and in Japan that are related to patterns of current drug abuse epidemics in these countries. These two nations have drug abuse problems with different histories and take different approaches currently to handling illicit drug marketing and use. Histories of opiate and cocaine abuse in the United States and of stimulant and inhalant abuse in Japan are discussed. The United States has experienced three heroin epidemics in the last three decades; cocaine addiction began to merit national concern by the end of the 1980s. In Japan, the first methamphetamine epidemic began after World War II; it was controlled in the 1950s. The current inhalant epidemic began in the late 1960s and was followed by the second methamphetamine epidemic that began in 1970; both are continuing to the present. The criminal justice system is always given first consideration when assessing societal measures employed to reduce drug use. Legal penalties for illicit drug offenses reflect the societal differences of these two nations with respect to the seriousness of particular types of crimes. Characteristics of the health care system of a nation may also influence patterns of drug abuse, particularly where functions of criminal justice and health care systems overlap. Health care systems in the United States and in Japan are based on different treatment philosophies and patients' expectations; these differences are discussed along with explanations of their potential influence on the epidemiology of drug abuse.

Attitude to Health↗

PubMedDate not supplied

A novel culture system for induction of T cell development: modification of fetal thymus organ culture.

We have previously found that the development of T cells predominantly of the T cell receptor alpha beta T cell lineage, which is comparable to that in the organ culture (OC) of fetal thymus at the air-medium border (AMB), could be induced in submersion OC of murine fetal thymus if the cultivation was performed in an environment containing O2 at 60-80%. This culture method is named high oxygen submersion (HOS)-OC. In the present work, we established a culture system where T cell development can be induced from thymic as well as fetal liver progenitors by cocultivating them in a 96-well U-bottom plate with a deoxyguanosine (dGuo)-treated fetal thymus lobe under HOS conditions. Differentiation and growth of T cells in this culture system were comparable to those seen in the previously devised micro i.t. system, where progenitor cells were injected with a microinjector into dGuo-treated lobes and were cultured under AMB conditions. A similar level of T cell development was induced by cocultivating such progenitors with small fragments of thymus lobes under HOS conditions. Moreover, it was possible to induce T cell development by culturing fetal thymus cells with thymic stromal cells prepared by treating dGuo-treated lobes with trypsin plus EDTA in a V-bottom plate under HOS conditions.

Animals↗

PubMedDate not supplied

Diagnosis of middle cerebral artery stenosis by transcranial color-coded real-time sonography.

BACKGROUND & PURPOSE: This study was performed to determine the usefulness of transcranial color-coded real-time sonography (TCCS) in detecting stenosis in the horizontal portion of the middle cerebral artery (MCA). METHODS: Using TCCS and the incident angle correction technique, we measured the peak-systolic flow velocity in bilateral MCAs in 45 consecutive patients in whom cerebral angiography was carried out within 1 week before or after TCCS. Three patients had a stenosis of 75% or greater and four had a unilateral occlusion of the extracranial internal carotid artery (ICA) (the ICS and ICO groups, respectively). Eight patients had a stenosis of 50% or greater (one bilateral and seven unilateral) (the M1S group). Four patients had unilateral distal occlusion of the horizontal portion of the MCA (the M1O group). Twenty-six patients had no significant extra- or intracranial stenosis on the ipsilateral or contralateral side (the control group). RESULTS: Mean peak-systolic flow velocity on the affected side was 83.0 +/- 20.8 cm/s in the ICS group, 59.8 +/- 23.2 cm/s in the ICO group, and 62.3 +/- 33.7 cm/s in the M1O group. In the control group, the mean peak-systolic flow velocity was 116.0 +/- 31.5 cm/s. In the M1S group, however, the mean peak-systolic flow velocity (334.2 +/- 35.7 cm/s) on the affected side always exceeded 180 cm/s (mean value +/- 2 SD in the control group), and was significantly higher than that in the other groups. The mean peak-systolic flow velocity in the M1S group increased with the grade of stenosis. CONCLUSION: The M1S group members could easily be distinguished from the other group members by their peak-systolic flow velocity in excess of 180 cm/s. Measurement of the peak-systolic flow velocity of the MCA by TCCS may help to identify a significant stenosis in the horizontal portion of the MCA.

Blood Flow Velocity↗

PubMedDate not supplied

Prospective randomized trial of 5-fluorouracil, doxorubicin, and mitomycin C for non-resectable pancreatic and biliary carcinoma: multicenter randomized trial.

BACKGROUND/AIMS: The efficacy of combination chemotherapy, which consists of fluorouracil, doxorubicin and mitomycin, was compared with that of palliative surgery-only in patients (control) having non-resectable pancreatic and biliary carcinomas in a multicenter randomized trial. METHODOLOGY: The patients were assigned to combination chemotherapy consisting of concomitant 5-fluorouracil 200 mg/m2, doxorubicin 15 mg/m2, and mitomycin 5 mg/m2 by intravenous administration. This combination chemotherapy was given concurrently as the initial dose within 1 week after palliative operation, and this regimen was repeated for at least 2 whole courses at 4-week intervals before the next course of therapy. Forty-two cases of this combination chemotherapy group and 41 of the control group were completely eligible for analysis. RESULTS: Regarding the overall 50% inhibition of tumor progression and that of gallbladder carcinoma, there were significantly better outcomes in the modified FAM therapy group. In this group, tumor reduction was achieved in 1 complete response (CR) and 2 partial response (PR) patients. With respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy, there was no difference between the groups. The most frequent adverse reactions were gastrointestinal manifestations such as anorexia, nausea, vomiting, and diarrhea; also noted was alopecia. CONCLUSIONS: Since this combination chemotherapy inhibited the tumor progression for significantly longer duration and, to a lesser extent, reduced the tumor size in non-resectable gallbladder carcinomas compared to a non-administrated chemotherapy group, this study will function as the basis for pursuing a more effective chemotherapy.

Adult↗