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Biomedical subjects

M Tanabe

Publications and source records attributed to M Tanabe.

At least 217 records · Page 12Linked to original sources

Prognostic prediction in neuroblastomas: clinical significance of combined analysis for Ha-ras p21 expression and N-myc gene amplification.

Ha-ras p21 expression and N-myc gene amplification were examined in 69 neuroblastomas and their clinical significance was analyzed retrospectively. Thirty-nine (89%) of forty-four patients who survived for more than 2 years after diagnosis showed high Ha-ras p21 expression, whereas 19 (76%) of 25 patients who died of progressive disease showed low Ha-ras p21 expression in their tumors. Although all 14 patients whose tumors exhibited N-myc gene amplification died of the disease, 11 other patients (56%) who died did not exhibit N-myc gene amplification. When we considered both low Ha-ras p21 expression and N-myc gene amplification as risk factors, 23 (92%) of the 25 patients who died had at least one of the two and thus could have been predicted to be high-risk patients at diagnosis. The combined analysis of the two factors should provide more accurate information pertinent to patient care.

Child, Preschool↗

Identification of human DAN gene, mapping to the putative neuroblastoma tumor suppressor locus.

The expression of DAN gene (previously designated as N03 gene) is significantly reduced in a variety of transformed rat fibroblasts, including v-src- (SR-3Y1), SV40- and v-mos-transformed 3Y1 cells, compared with that in parental 3Y1 cells. Recently, DAN gene has been shown to possess a tumor suppressive activity when it is overexpressed in SR-3Y1 cells (Ozaki & Sakiyama, 1994). To assess the involvement of DAN gene with human neoplasms, we have isolated human DAN counterpart from a normal lung cDNA library by using rat DAN cDNA as a probe, and determined its chromosomal location. Human DAN gene mapped to chromosome 1p36.11-p36.13, which is well known to show highly significant linkage with the genesis and/or progression of human neuroblastoma. Southern blot analysis on tumor DNA from 26 patients with neuroblastoma has detected three patients showing genomic rearrangement or deletion within or closely linked to the DAN gene locus. Collectively, we propose that human DAN gene is a possible candidate for a tumor suppressor gene of human neuroblastoma.

Amino Acid Sequence↗

[A comparative clinical study on the treatment of head and neck tumors by adjuvant chemotherapy with HCFU--Second Study by Kinki Head and Neck Tumor Study Group].

In the first study by the "Kinki Head and Neck Tumor Study Group," we performed a comparative study to investigate intergroup difference between a control group consisting of patients given radical treatment only, and a HCFU group consisting of patients receiving long-term administration of HCFU after radical treatment. We earlier reported that subsequent observations by stratification revealed a favorable tendency in the cumulative disease-free rate in Stage II and Stage III patients in the HCFU group. In the second study, the same methods of treatment as in the first study were compared in a prospective control study. No differences were found between the two groups in Stage II patients. In Stage III patients, however, the disease-free rate tended to increase significantly in the HCFU group as in the first study.

Adult↗

[An improved method of preparation of autopsied human inflated-fixed whole lungs for radiologic-pathologic correlation].

Inflated-fixed lung specimens, prepared using polyethyleneglycol 400, the standard Heitzman method have the disadvantage of bad staining. The authors attempted to improve this short-coming using human autopsied lungs and evaluated both microscopical findings and the degree of specimen inflation. Fifty-five human autopsied whole lungs were examined. Forty-six lungs with cannulation through the main bronchus were distended with 20% formalin, after clamping the cannula for 15 minutes to six days, formalin in lungs was expelled by air at 10 cm H2O pressure, then fixed with fixative-fluid containing polyethyleneglycol 400, 95% ethyl-alcohol, 40% formalin and water mixed in a ratio of 10:5:2:3. In 9 lungs without cannulation, formalin was expelled manually. The degree of distension of 46 of the 55 cannulated specimens was satisfactory (score A: 42 specimens, score B: 4 specimens). In 9 specimens without cannulation, inflation was poor (Score C). Good or excellent staining was obtained in 29 specimens (Score A: 10 specimens, Score B: 19 specimens), but 3 specimens were not be improved (Score C). Both inflation and staining were good in 21 specimens. This new method, requiring cannulation in the main bronchus, inflated-fixation with 20% formalin and expulsion of formalin by air prior to the standard Heitzman method enables both high quality staining and radiographs of the inflated-fixed lung specimen.

Biopsy↗

[Clinical trial of IVC filter to temporary placement].

We developed a new inferior vena caval filter to prevent pulmonary embolism for a patient with IVC thrombus. This filter made by covering top half of Dotter Intravascular Retriever catheter with Dacron mesh sheet, was placed in IVC through a 10 F sheath from right jugular vein. In one case, after anticoagulant therapy and thrombectomy using balloon catheter, many free-floating thrombus were trapped in this filter and were taken out from the IVC. This filter was useful for preventing pulmonary embolism when removing thrombus in IVC, iliac and lower extremity veins. We propose to call this device "Hino's filter".

Adolescent↗

Expression of alternatively spliced src messenger RNAs related to neuronal differentiation in human neuroblastomas.

Neuroblastoma, the most common malignant solid cancer of children, has an ability to differentiate in vitro and in vivo. This biological property has a significant influence upon the prognosis of patients with neuroblastomas. Neuronal cells express three alternatively spliced forms of c-src mRNA (nonneuronal c-src, neuronal c-srcN1, and neuronal c-srcN2), which are found at different levels in adult and fetal human brain tissue. In this study, the transcriptional levels of the three c-src mRNAs were examined in relation to the neural differentiation in eight human neuroblastoma cell lines and two clonal sublines and in seven primary neuroblastoma tissues by S1 nuclease protection assays. Neuronal c-srcN1 mRNA was expressed at high levels in neuroblastoma cell lines with the ability to differentiate but not in the cell lines lacking the capacity to mature in response to chemical inducers irrespective of N-myc gene amplification and overexpression. In terminally differentiated neuroblastoma cells, the expression of neuronal c-srcN2 mRNA, which was barely detectable at a steady-state level in the uninduced cells, increased to significant levels. Infantile neuroblastomas identified by mass screening tests expressed both neuronal c-srcN1 and c-srcN2 mRNAs at levels almost identical to that found in human brain tissue, but terminally differentiated neuroblastoma cells, neuroblastomas from older children identified based on clinical symptoms, did not. These results suggest that neuronal c-src expression and the ability of neuroblastomas to differentiate in vitro and in vivo may be correlated.

Base Sequence↗

[Experimental studies on Nicaraven as radioprotector--free radical scavenging effect and the inhibition of the cellular injury].

In the present study, firstly the antioxidant effect of Nicaraven was observed by examining the direct free radical scavenging effect with ESR. Dose dependent effects were shown in scavenging both of superoxide and hydroxyl radicals. In the study to check whether Nicaraven inhibits hydroxyl radical formation or degrades the spin adduct of DMPO with hydroxyl radical, the effect of Nicaraven was suggested that it inhibited hydroxyl radical formation itself. Secondly, it was recognized fluorophotometrically that the inhibiting effect of the agent on the superoxide and hydroxyl radicals promoted damage to benzoate, deoxyribose and some amino acids. The inhibiting effect was nearly the same as that of mannitol. Furthermore, the inhibition of the cellular injury induced by ferrous sulphate was investigated in NIH3T3 cells. The addition of Nicaraven to the cells after 6 hours of reaction with FeSO4, the inhibition of the cellular injury was significant (p < or = 0.01). The effect of Nicaraven was recognized as a radioprotector in vitro. The agent suggested to be able to produce recovery from the damage induced by irradiation at the cellular level.

3T3 Cells↗

Different effects of substitutions at residues 224 and 228 of MHC class I on the recognition of CD8.

Previous studies indicated that weak xenoresponse to HLA class I by mouse T cells is due to the inefficient interaction of mouse CD8 with the alpha 3 domain of HLA class I. The present study using chimeric H-2Kb molecules with recombinant alpha 3 domain between H-2Kb and HLA-B7 as well as single amino acid mutants of H-2Kb demonstrated that each substitution at residues 224 and 228 affects recognition of CD8-dependent mouse CTL clones. On the other hand, reactivity of IL-2-producing H-2Kb-specific T cell hybridoma transfected with mouse CD8 alpha was abrogated by substitution at residue 224 but not by that at residue 228. This indicates that the substitution at residue 228 affects recognition of CD8-dependent CTL but does not critically affect binding of CD8 to MHC class I molecules, although residue 224 abrogates binding of CD8. The model structure of the alpha 3 domain of H-2Kb suggests that the substitution at residue 224 induces conformational change of CD8 binding loop, whereas minimum structure change by the substitution at residue 228 is expected. It is therefore speculated that minimum structure change of CD8 binding loop by substitution at residue 228 may influence binding affinity of CD8, which abrogates recognition of CD8-dependent CTL but not IL-2 production of the CD8-dependent T cell hybridoma.

Amino Acid Sequence↗

Evaluation of bone marrow metastasis of neuroblastoma and changes after chemotherapy by MRI.

To evaluate the usefulness of MRI for diagnosing bone marrow metastasis of neuroblastoma, we compared MRI findings with histological findings. MRI was performed 26 times in 20 patients with neuroblastoma to detect metastasis to the bone marrow of the femur and tibia. Abnormal areas observed by MRI were histologically examined. The lesion visualized by MRI as a low-intensity area on T1-weighted images and as a high-intensity area on T2-weighted images was histologically confirmed to be neuroblastoma in 81% (17/21). The percentage varied according to the treatment state: 89% (8/9) by MRI imaging performed before the initiation of chemotherapy, 67% (6/9) within 3 weeks after cessation of chemotherapy (during chemotherapy), and 100% (3/3) in recurrent cases 1 year or more after chemotherapy. During the follow-up period after chemotherapy, tissue with signal intensities similar to that of bone marrow was observed in a speckled pattern in the intramedullary space on T1- and T2-weighted images. This tissue was histologically demonstrated to be normal bone marrow and was considered to be bone marrow remaining after chemotherapy. In this small series, histological findings supported the results of MRI, confirming the usefulness of MRI for diagnosing bone marrow metastasis of neuroblastoma. However, bone marrow metastasis after chemotherapy was difficult to evaluate by comparing signal intensities alone.

Adolescent↗

Paratesticular neuroblastoma with N-myc activation.

The authors describe a case of disseminated neuroblastoma discovered as a paratesticular tumor in a 7-month-old boy. The ectopic adrenal tissues adjacent to the paratesticular tumor and multiple lesions in the adrenal gland and skin suggested the possibility of multifocal primary tumors. Although infantile neuroblastoma diagnosed at less than 1 year of age generally responds well to treatment irrespective of distant metastases, metastases developed, and the boy died of disease within 7 months. All multiple lesions had amplification and overexpression of the N-myc protooncogene, which might explain the aggressive phenotype of this rare case.

Blotting, Northern↗

Imaging of neuroblastoma in patients identified by mass screening using urinary catecholamine metabolites.

Between April 1983 and August 1991, mass screening in Chiba Prefecture found 25 infants to be positive for neuroblastoma based on elevated urinary levels of catecholamine metabolites. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy (BS), and 67Ga scintigraphy (GS) detected neuroblastomas in 12 of the 25 infants. The primary site of tumor was the mediastinum in 1 patient, the adrenal gland in 7, retroperitoneum in 3, and pelvis in 1. To determine the accuracy of each imaging technique, the percent sensitivity (SE), percent specificity (SP), and percent accuracy (AC) were determined for each technique from surgical findings and a follow-up study. MRI showed the highest diagnostic accuracy (100% for SE, SP, and AC), followed by CT (100%, 92%, 96%), US (82%, 92%, 88%), BS (58%, 100%, 80%), and GS (42%, 85%, 64%) in that order. MRI is most suitable for the imaging of individuals judged to be positive in the mass screening for neuroblastoma because of the advantages of visualization of the spread of tumor and the relationship of tumor to the great blood vessels, important determinants of resectability and therapy.

Adrenal Gland Neoplasms↗

Transcriptional activation of the interleukin-6 gene by HTLV-1 p40tax through an NF-kappa B-like binding site.

The interleukin-6 (IL-6) gene is expressed by various stimuli including cytokines or viral infections, such as human T-cell leukemia virus type I (HTLV-1). However, it has not been well established how HTLV-1 induces the expression of the IL-6 gene. In the present study, we demonstrated that HTLV-1-derived transactivator protein, p40tax, could stimulate endogenous IL-6 gene expression. Furthermore, we showed that the NF-kappa B binding site (IL-6 kappa B site) located between -74 and -62 upstream of the cap site of the IL-6 gene was an essential cis-acting element for p40tax-mediated transactivation of the IL-6 gene expression by utilizing a series of 5' deletion mutants of the IL-6 5' flanking region as well as a construct with a mutated IL-6 kappa B site. We identified the presence of two nuclear factor complexes that bound to the IL-6 kappa B site. One was constitutively expressed, and the other was inducible by p40tax. Taken together, HTLV-1 p40tax directly induces IL-6 gene expression through the IL-6 kappa B site, indicating the close association between IL-6 overproduction and HTLV-1 infection.

Base Sequence↗

Graft-versus-host disease after brown Norway-to-Lewis and Lewis-to-Brown Norway rat intestinal transplantation under FK506.

In LEW rats treated daily with variable doses of FK506 for 14 days and weekly thereafter, successful intestinal transplantation from fully allogeneic BN donors never was complicated by fatal GVHD. In contrast, with LEW-to-BN transplantation, rejection was difficult to control and GVHD developed after the end of the daily treatment. However, FK506 in high daily doses continued after the initial 14-day course could prevent this GVHD or even reverse it after allowing its onset. Further experiments did not clarify why the BN rat was an "easy" donor and "difficult" recipient. In unaltered animals the lymphocyte population of normal LEW rats had a higher proportion of T cells, fewer B cells, and a lower CD4:CD8 ratio than normal BN rats. However, one-way MLR reactions of the BN and LEW combinations were generally similar in either direction and not affected differently by the addition of FK506 to the medium. The two-way lymphocyte traffic from graft to host lymphoid organs and vice versa also was similar with BN-to-LEW and LEW-to-BN models. The BN rat may be a useful tool to investigate inadequately explained mechanisms of GVHD.

Animals↗

Hamster-to-rat heart and liver xenotransplantation with FK506 plus antiproliferative drugs.

Heterotopic hamster hearts transplanted to unmodified LEW rats underwent humoral rejection in 3 days. Survival was prolonged to a median of 4 days with 2 mg/kg/day FK506. As monotherapy, 15 mg/kg/day cyclophosphamide greatly prolonged graft survival--far more than could be accomplished with RS-61443, brequinar (BQR), mizoribine, methotrexate, or deoxyspergualin. However, when FK506 treatment, which was ineffective alone, was combined with a short induction course (14 or 30 days) of subtherapeutic BQR, RS-61443, or cyclophosphamide, routine survival of heart xenografts was possible for as long as the daily FK506 was continued. In addition, a single large dose of 80 mg/kg cyclophosphamide 10 days preoperatively allowed routine cardiac xenograft survival under FK506. The ability of these antimetabolites to unmask the therapeutic potential of FK506 correlated, although imperfectly, with the prevention of rises of preformed heterospecific cytotoxic antibodies immediately postoperatively. As an adjunct to FK506, azathioprine was of marginal value, whereas mizoribine, methotrexate, and deoxyspergualin (DSPG) were of intermediate efficacy. After orthotopic hepatic xenotransplantation, the perioperative survival of the liver with its well-known resistance to antibodies was less dependent than the heart on the antimetabolite component of the combined drug therapy, but the unsatisfactory results with monotherapy of FK506, BQR, RS-61443, or cyclophosphamide were changed to routine success by combining continuous FK506 with a short course of any of the other drugs. Thus, by breaking down the antibody barrier to xenotransplantation with these so-called antiproliferative drugs, it has been possible with FK506 to transplant heart and liver xenografts with consistent long-term survival of healthy recipients.

Animals↗

Local cerebral glucose utilization in rats with decerebrate rigidity and effects of centrally acting muscle relaxants, diazepam and tizanidine.

Local cerebral glucose utilization (LCGU) was investigated in rats with decerebrate rigidity using the [14C]2-deoxyglucose (2DG) method in order to identify the site responsible for the rigidity. LCGU was increased in the medial vestibular nucleus, the fastigial nucleus, the interpositus nucleus and the dentate nucleus during decerebrate rigidity. Diazepam and tizanidine, centrally acting muscle relaxants, reduced the increase of LCGU in the vestibular and cerebellar nuclei. These results suggest that the vestibular and cerebellar nuclei are the possible sites responsible for the development of decerebrate rigidity and the action of some centrally acting muscle relaxants.

Animals↗

Cholesterol biosynthesis inhibitory component from Zingiber officinale Roscoe.

We previously reported on the isolation and identification of (E)-8 beta,17-epoxylabd-12-ene-15,16-dial (ZT) from ginger (rhizome of Zingiber officinale Roscoe, Zingiberaceae). In this paper, the pharmacological effects of ZT are reported. The experimental mouse hypercholesterolemia induced by Triton WR-1339 was treated after oral administration of ZT. In homogenated rat liver with ZT, cholesterol biosynthesis was decreased. In addition, the same activity was observed in the homogenated rat liver which was resected after the oral administration of ZT. According to the results of general pharmacological screening, no remarkable activity of ZT was observed except for an inhibitory effect on the cholesterol biosynthesis.

Animals↗