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Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 127 records · Page 7Linked to original sources
PubMed1998

Biochemical and functional analysis of highly phosphorylated forms of c-Jun protein.

We report here that, upon UV irradiation or growth stimulation, endogenous c-Jun (40 kDa) in chicken embryo fibroblasts (CEF) is converted into several forms with apparently higher molecular weights in SDS-polyacrylamide gel electrophoresis (45, 44, 42 kDa). Two of the bands (44 and 45 kDa) were transient after growth stimulation, but were much more persistent after UV irradiation. In both cases, the drastic mobility shifts were accompanied with the activation of endogenous JNK activity but not of MAPK activity, and the bands were shown to represent different phosphorylation states of c-Jun rather than ubiquitinated c-Jun. Biochemical analysis indicated that phosphorylation at Ser63 and Ser73 was not sufficient to produce these drastic mobility shifts, which additionally required phosphorylation at Thr91 and Thr93. Substitution of both Ser63 and Ser73 with either Ala or Asp had no significant effect on the transforming activity of c-Jun, but the mutants failed to show drastic mobility shifts even after UV irradiation. These results indicate that Ser63 and Ser73 are essential for the drastic mobility shifts and further suggest that the highly phosphorylated forms of c-Jun are not directly involved in cellular transformation.

Amino Acid Sequence↗
PubMed1998

Antibody to thrombin receptor inhibits neointimal smooth muscle cell accumulation without causing inhibition of platelet aggregation or altering hemostatic parameters after angioplasty in rat.

An antibody was raised in rabbits against SFFLRNPSEDTFEQF peptide, which is an NH2-terminal peptide of the thrombin-cleaved rat thrombin receptor. In vitro, the antibody inhibited rat smooth muscle cell proliferation but had no effect on rat platelet aggregation or clotting time. These data indicate that the antibody is a specific blocker of the thrombin receptor-signaling pathway in rat smooth muscle cells but does not work as a blocker in rat platelets, suggesting the existence of a second thrombin receptor in the platelets. Using an in vivo balloon catheter-induced injury model in rats, we examined the effect of the anti-rat thrombin receptor IgG on intimal smooth muscle cell accumulation 2 weeks after angioplasty. Analysis of the ratio of intimal to medial cross-sectional areas showed that injection of immune IgG resulted in 43.7% and 53.1% reduction (P<0.01) of neointimal smooth muscle cell accumulation compared with saline and nonimmune IgG treatment, respectively. Moreover, the injection of immune IgG caused a significant decrease of thrombin receptor mRNA expression and also 40.5% and 43.0% decreases (P<0.01) of the proliferating cell nuclear antigen (PCNA) index in the intima compared with the PCNA index after saline and nonimmune IgG treatment, respectively. The suppression of the PCNA index was also observed in the immune IgG-treated group at an early stage after angioplasty. These results suggest that thrombin receptor activation is involved in the proliferation and accumulation of neointimal smooth muscle cells induced by balloon injury.

Angioplasty↗
PubMed1998

Corticostriatal input zones from the supplementary motor area overlap those from the contra- rather than ipsilateral primary motor cortex.

To investigate the degree of convergence of corticostriatal inputs from the primary motor cortex (MI) and the supplementary motor area (SMA), we analyzed the extent to which corticostriatal inputs from forelimb representations of these motor-related areas spatially overlap in the macaque monkey. Of particular interest was that corticostriatal input zones from SMA overlapped those from MI of the contralateral hemisphere more extensively than from MI of the ipsilateral hemisphere.

Animals↗
PubMed1998

Induction of hydrogen peroxide production and Bax expression by caspase-3(-like) proteases in tyrosine kinase inhibitor-induced apoptosis in human small cell lung carcinoma cells.

In our previous studies (S. Simizu, et al., 1996, Cancer Res. 56, 4978-4982), we reported that apoptosis of human small cell lung carcinoma (SCLC) cells induced by protein tyrosine kinase inhibitors, such as erbstatin and herbimycin A, was mediated by H2O2 via a newly synthesized protein(s). In the present study, we demonstrated that induction of apoptosis by erbstatin resulted in activation of caspase-3(-like) proteases, which are interleukin-1 beta-converting enzyme family proteases (caspases) and that inhibition of these protease activities reduced the extent of cell death and H2O2 generation. We also demonstrated that expression of apoptotic protein Bax was induced by erbstatin. Erbstatin-induced Bax expression was inhibited by the inhibitor of caspase-3(-like) proteases. These results indicate that generation of intracellular H2O2 and Bax expression in tyrosine kinase inhibitor-induced apoptosis were modulated by the activation of caspase-3(-like) proteases in SCLC cells.

Apoptosis↗
PubMed1998

Video-assisted thoracic surgery through a single skin incision.

OBJECTIVE: To develop a minimally invasive video-assisted thoracic surgery technique. DESIGN: Case series. SETTING: University referral center. PATIENTS: Six consecutive patients with a pneumothorax who underwent video-assisted thoracic surgery through a single skin incision. INTERVENTIONS: A flexible digital bronchoscope was placed in a scope guide. A single 2.0-cm skin incision was made in the midaxillary line. The entire lung was carefully explored. An endoscopic stapling device was then inserted, and the lung resection was performed through a single skin incision. PRIMARY OUTCOME MEASURES: Operative time, estimated amount of blood loss, operative complications, and postoperative air leakage were recorded. RESULTS: The video-assisted thoracic surgery procedure through a single incision was successful in all 6 patients. There were no associated complications at 1-year follow-up. CONCLUSIONS: We were able to perform the video-assisted thoracic surgery procedure through a single skin incision using a scope guide and a flexible scope that enables visualization of the entire pleural cavity, providing even laser ablation. This new technique can be used to treat patients with pneumothoraces without the need for additional skin incisions.

Adult↗
PubMed1998

High frequency expressions of CD44 standard and variant forms in non-small cell lung cancers, but not in small cell lung cancers.

BACKGROUND AND OBJECTIVES: Organ specificity has been demonstrated in the mode of CD44 expression among several cancers. METHODS: We examined the expressions of CD44 standard (CD44s) and CD44 variants (CD44v) in 14 cell lines (small cell lung cancer (SCLC): 5, non-small cell lung cancer (NSCLC): 9 and 20 surgically resected samples (SCLC: 7, NSCLC: 13) of lung cancer using reverse transcription polymerase chain reaction and immunohistochemistry. RESULTS: Although both NSCLC and SCLC expressed CD44s, the frequency and intensity of CD44s expression in NSCLC were different from those in SCLC: cell lines, 89% vs. 40%; tumor samples, 100% (diffusely stained) vs. 57% (focally stained). CD44s expression was partially or completely repressed in SCLC. However, NSCLC frequently expressed CD44v, but SCLC expressed infrequently: cell lines, 67% vs. 20%; tumor samples, 69% vs. 0%. The N-417 line, which only expressed some CD44v in SCLC, falls SCLC and NSCLC both in biomarkers and in growth patterns. CONCLUSIONS: CD44 expression was repressed in SCLC but was enhanced in NSCLC.

Adenocarcinoma↗
PubMed1998

Homozygous deletion and frequent allelic loss of the 21q11.1-q21.1 region including the ANA gene in human lung carcinoma.

The frequent occurrence of 21q deletions in human non-small cell lung carcinoma (NSCLC) indicates the presence of a tumor suppressor gene on this chromosome arm. Since the ANA (Abundant in Neuroepithelium Area) gene, a member of an antiproliferative gene family, was mapped to 21q11.2-q21.1, we searched for genetic alterations of the ANA gene in human lung cancers. The gene was homozygously deleted in a human NSCLC cell line, Ma17. The gene was mapped in the 0.33 Mb Not1 fragment at 21q21.1 of the Not1 restriction map for 21q. Loss of heterozygosity (LOH) at this locus was detected in 24/47 (51.1%) of NSCLC, and the frequency of LOH in brain metastases was significantly higher than that in stage I-II primary tumors (P = 0.018). These results suggested that the homozygously deleted region harbors a novel tumor suppressor gene involved in NSCLC progression. Since mutation of the ANA gene was not detected in other lung cancer cell lines and fresh lung tumors with LOH at this locus, it is unlikely that the ANA gene is a target gene inactivated by two mutational events in this chromosomal region. Physical mapping of the homozygously deleted region showed that the deletion had occurred interstitially at 21q11.1-q21.1 and the size of the deletion was estimated as being more than 3 Mb. Our mapping results will facilitate further efforts to identify a tumor suppressor gene on 21q.

Aged↗
PubMed1998

Surgical treatment of Cronkhite-Canada syndrome associated with protein-losing enteropathy: report of a case.

PURPOSE: The case of a patient with Cronkhite-Canada syndrome, who developed a protein-losing enteropathy, is reported. METHODS: After localization of the protein-losing region, a right colectomy was performed. RESULTS: Hypoproteinemia and ectodermal changes improved postoperatively. CONCLUSIONS: Surgery is an effective treatment for protein-losing enteropathy in Cronkhite-Canada syndrome. Ectodermal changes improve after correcting malnutrition.

Female↗
PubMed1998

Relationship between skeletal uptake of 99mTc-HMDP and bone mineral density in elderly women.

The relationship between bone mineral density in elderly women and the pattern of skeletal uptake of 99mTc-HMDP, especially in regard to skull uptake, was investigated. The whole-body skeletal uptake (WBSU) and whole-body skeletal tracer distribution patterns were studied in 86 disease-free women on bone scintigraphy with 99mTc-hydroxy-methylene-diphosphonate (HMDP). Bone scans were quantified by setting regions of interest (ROI) and bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry in all patients. WBSU and the skeletal distribution pattern were compared with bone mineral densities of the entire skeleton as well as selected regions. WBSU was high in the elderly and negatively correlated with regional bone mineral densities (r = -0.403 to -0.534). Among the regions, uptake by the skull increased with age more than in other regions in women and had the highest negative correlation with the bone mineral density. The skull uptake correlated negatively with total body BMD (r = -0.583) and with lumbar BMD (r = -0.561, p < 0.0001). Our results show that increased radionuclide uptake in bone scintigraphy, especially skull uptake was associated with decreased bone mineral density in elderly women, so that, increased skull uptake in elderly women would be a scintigraphic sign of post-menopausal or senile osteopenia.

Absorptiometry, Photon↗
PubMed1998

Vertebral fracture assessment using the lateral scoutview of computed tomography in comparison with radiographs.

Semiquantitative vertebral fracture assessment was compared between lateral computed tomography (CT) scoutviews and conventional thoracolumbar spinal radiographs. Vertebral levels T4-L4 were assessed by both techniques in a group of 56 women (mean age 60 +/- 13 years). In order to compare inter- and intra-observer variabilities for the two techniques, the images were analyzed twice by two independent observers, and percentage agreement and kappa statistics were measured both between readings and between observers. Percentage agreement and kappa statistics were also used to quantify differences between techniques. In the CT scoutviews, noise and artifacts from overlying tissues in the thoracic spinal levels rendered 3.4% of the vertebrae unreadable for the first observer and 8.3% for the second observer. For the CT scoutviews the agreement between readings was 98.1%, 97.3% and 100% (kappa = 0.87, 0.83 and 1.0) on T4-L12, T4-12 and L1-4, respectively for the first observer, and 97.8%, 97.1% and 99.5% (kappa = 0.79, 0.73 and 0.92) for the second observer. For the lateral radiographs, the agreement between readings was 97.7%, 96.9% and 100% (kappa = 0.87, 0.85 and 1.0) on T4-L12, T4-12 and L1-4, respectively for the first observer, and 98.4%, 97.7% and 99.5% (kappa = 0.86, 0.82 and 0.95) for the second observer. The agreement between observers was 96.1%, 94.4% and 100% (kappa = 0.68, 0.58 and 1.0) on T4-L12, T4-12 and L1-4, respectively for the CT scoutviews and 96.8%, 95.9% and 99.0% (kappa = 0.79, 0.76 and 0.91) for the lateral radiographs. The inter-technique was 95.8%, 94.2% and 99.5% (kappa = 0.73, 0.68 and 0.95) on T4-L12, T4-12 and L1-4, respectively for the first observer and 95.6%, 94.2% and 99.0% (kappa = 0.64, 0.55 and 0.90) for the second observer, with the scoutview technique detecting, on average, 23% fewer fractures than the lateral radiographs. Although the vertebral fracture detection in lumbar spine is quite comparable to that of conventional radiographs, given its reduced sensitivity for vertebral fracture detection in thoracic spine, the lateral CT scoutview technique should not be substituted for conventional radiographs where diagnosis of all vertebral fractures is of primary importance.

Adult↗
PubMed1998

Corticostriatal projections from the somatic motor areas of the frontal cortex in the macaque monkey: segregation versus overlap of input zones from the primary motor cortex, the supplementary motor area, and the premotor cortex.

It is an important issue to address the mode of information processing in the somatic motor circuit linking the frontal cortex and the basal ganglia. In the present study, we investigated the extent to which corticostriatal input zones from the primary motor cortex (MI), the supplementary motor area (SMA), and the premotor cortex (PM) of the macaque monkey might overlap in the putamen. Intracortical microstimulation was performed to map the MI, SMA, and dorsal (PMd) and ventral (PMv) divisions of the PM. Then, two different anterograde tracers were injected separately into somatotopically corresponding regions of two given areas of the MI, SMA, PMd, and PMv. With respect to the PMd and PMv, tracer injections were centered on their forelimb representations. Corticostriatal input zones from hindlimb, forelimb, and orofacial representations of the MI and SMA were, in this order, arranged from dorsal to ventral within the putamen. Dense input zones from the MI were located predominantly in the lateral aspect of the putamen, whereas those from the SMA were in the medial aspect of the putamen. On the other hand, corticostriatal inputs from forelimb representations of the PMd and PMv were distributed mainly in the dorsomedial sector of the putamen. Thus, the corticostriatal input zones from the MI and SMA were considerably segregated though partly overlapped in the mediolateral central aspect of the putamen, while the corticostriatal input zone from the PM largely overlapped that from the SMA, but not from the MI.

Animals↗
PubMed1998

Accuracy and diagnostic sensitivity of radiographic absorptiometry of the second metacarpal.

The accuracy of a radiographic absorptiometry (RA) technique called digital image processing (DIP), discriminative ability of RA for osteoporotic fracture, and the relationship between RA and dual X-ray absorptiometry (DXA) of the spine and forearm were evaluated. We measured 16 cadaver hands, 32 healthy non-black premenopausal women, 39 healthy non-black postmenopausal women, and 35 non-black osteoporotic postmenopausal females. The overall correlation between the ash weights of the entire metacarpal and the DIP values was excellent (r = 0.954, P < 0.001, SEE = 0.14, CV = 6.4%). Short-term precision error of DIP was 3.5%. Age-related bone loss determined by DIP is comparable to that of spinal and forearm DXA: annual BMD decreases were 0.46% for DIP, 0.45% for forearm, and 0.32% for the spine. DIP of the 2nd metacarpal shows a gradient of risk for spinal fracture only slightly below that of forearm DXA, but substantially below that of spinal DXA. Age-adjusted odds ratios were 1.81 for RA, 2.45 for spinal DXA, and 1.94 for forearm DXA.

Absorptiometry, Photon↗
PubMed1998

Activity of gemcitabine in non-small-cell lung cancer: results of the Japan gemcitabine group (A) phase II study.

PURPOSE: This phase II study was conducted to determine the response and toxicity of gemcitabine (2',2'-difluorodeoxycytidine) in chemotherapy-naive patients with non-small-cell lung cancer (NSCLC). METHODS: A group of 73 patients were entered into the study. The patients had received no previous chemotherapy and all had measurable disease. The initial starting dose of gemcitabine was 1000 mg/m2 per week x 3 followed by a week of rest, and was escalated for the next cycle to 1250 mg/m2, provided there were no signs of hematologic toxicity (WBC < 3000/microl and/or platelets < 70,000/microl) in the previous cycle. RESULTS: Among 73 eligible patients, there were 19 partial responses (PRs), with an overall response rate of 26.0% (95% confidence interval 16.5-37.6%). The response rate for stage IIIa and IIIb disease was significantly higher than that for stage IV disease [41.4% (12/29) vs 15.9% (7/44); P = 0.028]. The median duration of response in patients showing a PR was 4.6 months (1.7 10.4 months). The median number of cycles given was two per patient (range one to seven). Grade 3 anemia, leukopenia and neutropenia occurred in 15 patients (20.5%), 7 patients (9.6%) and 20 patients (27.4%), respectively. Grade 3 thrombocytopenia occurred in one patient (1.4%) which was not associated with any bleeding. There was no evidence of cumulative toxicity in the later courses of gemcitabine treatment with regard to leukopenia and thrombocytopenia. Other toxicities, including hepatic toxicity, fatigue, nausea/vomiting and fever were mild (grade 2 or less) and transient. One patient was withdrawn from the trial because of a rash. Pulmonary toxicity was experienced in two patients and one patient died of respiratory insufficiency which was thought to be drug-related. CONCLUSIONS: Gemcitabine as a single agent has proven to be an active drug for NSCLC with a favorable, generally mild side-effect profile. Further trials in combination with other agents for this disease are currently underway.

Adult↗
PubMed1998

Involvement of intestinal P-glycoprotein in the restricted absorption of methylprednisolone from rat small intestine.

The interaction between steroid hormones and intestinal P-glycoprotein was investigated by measuring intestinal absorption from rat small intestine in situ. Prednisolone and hydrocortisone were rapidly absorbed from the entire small intestine. In contrast, methylprednisolone absorption was significantly retarded in jejunum and ileum by an intestinal efflux system. In the presence of verapamil an quinidine, the retarded absorption of methylprednisolone was completely recovered, suggesting that P-glycoprotein is responsible for the unique features of methylprednisolone absorption. A requisite for the substrate of intestinal P-glycoprotein seemed to be 6 alpha-methyl group in the steroid structure. Substrate specificity of intestinal P-glycoprotein to steroid hormones was shown to be in part different from those in other tissues such as adrenal gland. Little of all three steroid hormones disappeared in the supernatant of mucosal homogenate from rat small intestine, indicating that intestinal metabolism of these steroid hormones was relatively small.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Chemo-enzymatic synthesis of galactosylmaltooligosaccharidonolactone as a substrate analogue inhibitor for mammalian alpha-amylase.

We performed chemo-enzymatic transformation of maltooligosaccharides into both end-modified oligosaccharidonolactones of potential use as substrate analogue inhibitors for mammalian alpha-amylases. Enzymatic modification of the non-reducing end glucosyl residue of the maltooligosaccharide was first performed by transglycosylation with beta-D-galactosidase from Bacillus circulans. When maltotriose and maltotetraose were the acceptors, the enzyme regioselectively synthesized 4(3)-O-beta-D-galactosyl maltotriose (LG3) and 4(4)-O-beta-D-galactosyl maltotetraose (LG4) from lactose as a donor. LG4 was further selectively hydrolyzed with a specific alpha-amylase to afford 4(2)-O-beta-D-galactosyl maltose (LG2). The anomer hydroxyl groups of LG2 and LG3 were chemically oxidized to give the corresponding lactones, 4(2)-O-beta-D-galactosyl maltobionolactone (LG2O) and 4(3)-O-beta-D-galactosyl maltotrionolactone (LG3O), respectively. LG2O and LG3O, which are competitive inhibitors for mammalian alpha-amylases, exhibited Ki values of the order of 2.8-18.0 microM, with p-nitrophenyl alpha-maltopentaoside (G5P) as the substrate. On 1H-NMR analysis, these oligosaccharidonolactones were shown to be transformed into the corresponding aldonic acid forms with time in an aqueous solution. In this case, the lactone form was essential for the occurrence of the alpha-amylase inhibitor.

Animals↗