Biomedical subjects

S Takashima

Publications and source records attributed to S Takashima.

At least 145 records · Page 8Linked to original sources

PubMed2000

Comparative analysis of the genomic structures and promoter activities of mouse Siaalpha2,3Galbeta1,3GalNAc GalNAcalpha2, 6-sialyltransferase genes (ST6GalNAc III and IV): characterization of their Sp1 binding sites.

The genomic organization of the genes encoding the mouse N-acetylgalactosamine alpha2,6-sialyltransferase specific for Siaalpha2,3Galbeta1,3GalNAc (ST6GalNAc III and IV) has been determined. The ST6GalNAc III gene spans over 120 kilobases of genomic DNA with 5 exons; on the other hand, the ST6GalNAc IV gene spans over 12 kilobases of genomic DNA with 6 exons. But the exon-intron boundaries of these genes are very similar. The 5'-flanking regions of these genes do not contain a TATA- or CAAT-box but have three putative Sp1 binding sites for each promoter. Transient transfection experiments demonstrated functional promoter activity in an ST6GalNAc III-expressing cell line, P19, for the ST6GalNAc III promoter, and in an ST6GalNAc IV-expressing cell line, NIH3T3, for the ST6GalNAc IV promoter. Mobility shift assaying and mutational analysis of the promoter region indicated that two of the three Sp1 binding sites are involved in the transcriptional regulation of the ST6GalNAc III gene in P19 cells, while all three Sp1 binding sites are involved in the transcriptional regulation of the ST6GalNAc IV gene in NIH3T3 cells.

3T3 Cells↗

PubMed2000

Molecular cloning and genomic analysis of mouse GalNAc alpha2, 6-sialyltransferase (ST6GalNAc I).

cDNA clones encoding mouse GalNAc alpha2,6-sialyltransferase (ST6GalNAc I) were isolated from a mouse submaxillary gland cDNA library. The deduced amino acid sequence of cDNA clones is 526 amino acids in length and has highly conserved motifs among sialyl transferases, sialyl motifs L, S, and VS. The expressed recombinant enzyme exhibited similar substrate specificity to chicken ST6GalNAc I. The mouse ST6GalNAc I gene was expressed in submaxillary gland, mammary gland, colon, and spleen. The mouse ST6GalNAc I gene was also cloned from a mouse genomic library, which was divided into 9 exons spanning over 8 kilobases of genomic DNA. The genomic structure of the mouse ST6GalNAc I gene was similar to that of the mouse ST6GalNAc II gene. Unlike the ST6GalNAc II gene, however, which has a housekeeping gene-like promoter with GC-rich sequences, the ST6GalNAc I gene has two promoters and they do not contain GC-rich sequences but contain putative binding sites for tumor-associated transcription factors such as c-Myb, c-Myc/Max, and c-Ets. Analysis of the 5'-RACE PCR products suggested that the mouse ST6GalNAc I gene expression is regulated by these two promoters in tissue-specific manners.

Amino Acid Sequence↗

PubMed2000

Genomic organization and transcriptional regulation of the mouse GD3 synthase gene (ST8Sia I): comparison of genomic organization of the mouse sialyltransferase genes.

The genomic organization of the gene encoding the mouse GD3 synthase (ST8Sia I) has been determined. The mouse ST8Sia I gene spans over 100 kilobases of genomic DNA with a unique genomic structure of 5 exons. Analysis of the sequence immediately upstream of the transcription initiation site revealed that the ST8Sia I promoter contained no canonical TATA- or CCAAT-box, but contained a putative Sp1 binding site. Transient transfection experiments demonstrated functional promoter activity of the ST8Sia I promoter in an ST8Sia I-expressing cell line, P19, but not in an ST8Sia I-nonexpressing cell line, NIH3T3. Mobility shift assay and mutation analysis of the promoter region indicated that the Sp1 binding site is involved in the transcriptional regulation of the ST8Sia I gene in P19 cells. Here, the genomic structural analyses of mouse sialyltransferase genes are summarized and the genomic structures of these genes are compared.

Animals↗

PubMed2000

Head and neck lesions: determination of an optimal MT technique for prediction of malignancies.

RATIONALE AND OBJECTIVES: To determine an optimal magnetization transfer (MT) technique for diagnosis of malignancies in the head and neck. METHODS: Lesion magnetization transfer ratios (MTRs) and lesion-to-muscle MTRs were prospectively measured in 52 head and neck lesions of 52 patients at frequency offsets of 0.3, 0.5, and 1 kHz from water resonance. The diagnostic capability for each MT pulse was calculated by using receiver operating characteristic (ROC) curves, and an optimal MT technique was determined for diagnosis of malignancies. RESULTS: The lesion MTRs and the lesion-to-muscle MTRs in malignant tumors were statistically significantly greater than those in benign lesions at both 0.5- and 1-kHz MT pulses, but no significant differences were noted between them at the 0.3-kHz MT pulse. Diagnosis with the lesion-to-muscle MTRs was better than that with the lesion MTRs at each MT pulse. Among all MTRs, lesion-to-muscle MTRs at the 1-kHz MT pulse showed the highest diagnostic capability for malignancies (area under the ROC curve = 0.82+/-0.06). With a lesion-to-muscle MTR at a 1-kHz MT pulse of 0.61 or greater, the highest accuracy of 85% was attained with 90% sensitivity and 77% specificity. CONCLUSIONS: Lesion-to-muscle MTRs at a 1-kHz MT pulse were optimal for diagnosis of malignancies in the head and neck.

False Positive Reactions↗

PubMed2000

Intrapleural rupture of a cystic thymoma.

Although cystic degeneration of a thymoma is not uncommon, rupture of a cystic thymoma is rare. The authors report a patient with sudden chest pain and dyspnea due to rupture of a cystic thymoma into the right pleural space.

Aged↗

PubMed2000

Comparison of genomic structures of four members of beta-galactoside alpha2,3-sialyltransferase genes in the mouse.

The mouse genes encoding beta-galactoside alpha2, 3-sialyltransferases-Siat4 (ST3Gal I), Siat5 (ST3Gal II), Siat3 (ST3Gal III), and Siat4c (ST3Gal IV)-were isolated and characterized. Siat4 and Siat5 comprise 8.4 and 14 kb, respectively, and are composed of six exons each. The genomic structures of the two genes were similar. Siat3 and Siat4c comprise over 100 and 9.7 kb, respectively, and are composed of 12 and 10 exons, respectively. Although the genomic sizes of these genes differ, some of their exon structures are significantly similar. These results suggest that the gene pair Siat4 and Siat5 arose from a common ancestral gene, as did the two genes Siat3 and Siat4c.

Amino Acid Motifs↗

PubMed2000

Roles of glutamate transporter and receptors, poly (ADPribose) polymerase, and transforming growth factor-beta1 in pontosubicular neuron necrosis.

The expression of neuron-type glutamate transporters (EAAC-1), AMPA glutamate receptor subunits (GluR1 and GluR2/3), polyadenosine (5'diphosphate-ribose) polymerase (PARP), and transforming growth factor-beta1 was investigated in 20 cases of neonatal pontosubicular neuron necrosis and 12 gestational-age matched controls. Developmental immunoreactivities of EAAC-1, GluR1, and GluR2/3 appeared in the neurons of the pontine nuclei at 29 to 30 weeks' gestation in controls, and then gradually increased with age. However, these activities were decreased in the pontine nucleus of patients with pontosubicular neuron necrosis. Decreases in these immunoreactivities might indicate early degeneration of neurons. Although PARP and transforming growth factor-beta1 immunoreactivity was insignificant or very weak in the pontine nuclei at any age in controls, PARP was markedly expressed in karyorrhectic neurons of the pontine nucleus in patients with pontosubicular neuron necrosis. Transforming growth factor-beta1 immunoreactivity was observed in nonkaryorrhectic neurons of the pontine nuclei. PARP could contribute to the pathogenesis of pontosubicular neuron necrosis more than EAAC-1 or GluR1 or GluR2/3. Transforming growth factor-beta1 could play a role in the protection and repair of damaged neurons.

ATP-Binding Cassette Transporters↗

PubMed2000

Phase I and pharmacokinetic study of a new taxoid, RPR 109881A, given as a 1-hour intravenous infusion in patients with advanced solid tumors.

PURPOSE: RPR 109881A is a new semisynthetic taxoid compound that has a similar mechanism of action to docetaxel. The purpose of this phase I study was to characterize the maximum-tolerated dose (MTD), toxicity profile, pharmacokinetic profile, and antitumor effects of this agent. PATIENTS AND METHODS: Nineteen eligible patients with advanced solid tumors were enrolled. RPR 109881A was administered as a 1-hour intravenous infusion every 3 weeks at doses ranging from 15 to 75 mg/m(2). Pharmacokinetic evaluation was performed at the first cycle. RESULTS: Neutropenia (febrile neutropenia) and fatigue were dose-limiting toxicities at doses of 60 and 75 mg/m(2) and seemed to be dose-related. Both thrombocytopenia and anemia were infrequent. Nonhematologic toxicities were generally mild. Pharmacokinetic studies indicated that RPR 109881A plasma disposition was bi- or triphasic, with a high total plasma clearance, a large volume of distribution, and a long terminal half-life. The area under the concentration-time curve (AUC) and the peak concentration of RPR 109881A seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics. Urinary excretion over 48 hours was low, with a mean of 0.8 +/- 0.36% of the administered dose. A significant relationship existed between the percentage decrease of neutrophil counts and the AUC of RPR 109881A. Among 18 assessable patients, two partial and two minor responses were documented. CONCLUSION: RPR 109881A was found to be a well-tolerated and promising taxoid agent. The MTD was 75 mg/m(2), and the recommended dose for phase II study was 60 mg/m(2) as a 1-hour infusion every 3 weeks.

Adult↗

PubMed2000

Hypocapnia under hypotension induces apoptotic neuronal cell death in the hippocampus of newborn rabbits.

We investigated the adverse effect of hypocapnia on the neonatal rabbit brain. Two-week-old Japanese white rabbits were assigned to three groups, hyperventilation (H group), ischemia (I group), or hypocapnia with ischemia (HI group) and then subjected for 1.5 h with simultaneous measurement of the mean arterial blood pressure (MABP) and intracranial Hb concentration changes. Marked reductions of PaCO2 and MABP were induced in the hyperventilation-loaded groups and the ischemia-loaded groups, respectively. The intracranial oxyhemoglobin and total Hb concentrations decreased slightly in the H group and markedly in the I and HI groups after the start of experimental protocols, although there were no statistical differences between the I and HI groups. Animals were killed at 24 h after experiments and then subjected to pathologic examination. Damaged neurons with shrunken cell bodies and nuclear changes were found on light microscopic examination, mainly in the pyramidal cell layer of the subiculum and cornu ammonis 1. The numerical density of damaged neurons was significantly higher in the HI group than those in the H or I groups (p < 0.05). These damaged neurons were positive on DNA nick end labeling. A DNA ladder was detected on electrophoresis with a DNA sample extracted from hippocampal tissue in the HI group, but not in the other two groups. On electron microscopic examination, not only condensation of the nucleus but also disruption of mitochondria and the cell membrane were detected. These results suggested that hypocapnia under hypotension might cause neuronal cell death in the hippocampus of neonatal rabbit. Not only ischemia but also a metabolic change induced by hypocapnia might contribute to this apoptotic neuronal cell damage.

Animals↗

PubMed2000

Successful launch of cardiac transplantation in Japan. Osaka University Cardiac Transplant Program.

Cardiac transplantation has been established as a therapeutic strategy for patients with end-stage heart failure. In Japan, however, cardiac transplantation has not been performed since the first case in 1968, and even now, after legislation for the approval of brain death was passed in 1997, it is still not performed regularly. Following long and steady efforts to enlighten Japanese society about the concept of brain death and the importance of organ transplantation, the first cardiac transplantation under the new legislation was successfully performed at Osaka University Hospital on February 1999. The patient was 47-year-old male in the dilated phase of hypertrophic cardiomyopathy who had been supported with an implantable left ventricular assist device. This article briefly reviews the situation prior to the first case of cardiac transplantation under the new legislation and discusses the current status of the therapy in Japan.

Adolescent↗

PubMed2000

Characteristics of small lung cancers invisible on conventional chest radiography and detected by population based screening using spiral CT.

Conventional chest radiography (CXR) is a poor diagnostic tool for detecting lung cancers at a surgically curable stage. To determine the visibility of peripheral small lung cancers on CXR, we retrospectively examined the usefulness of CXR using a consecutive series of 44 cases detected on CT screening and later confirmed by histopathology. All cases had been detected by low dose CT during a population based screening trial for lung cancer. The control group consisted of 48 chest radiographs of normal subjects. Tumour diameters ranged from 6 mm to 45 mm, with 95% (42/44) < or = 20 mm, and 5% (2/44) > 20 mm. CXR failed to detect 77% (34/44) of all cancers, including 79% (33/42) < or = 20 mm and 50% (1/2) > 20 mm. Of the 42 lung cancers < or = 20 mm, 74% (31/42) were located in the well penetrated lung zones and 71% (22/31) of these were missed on CXR. 26% (11/42) were concealed by hilar vessels, mediastinum, heart or diaphragm, and all (11/11) of these were missed on CXR. 93% (39/42) of the lung cancers < or = 20 mm were adenocarcinomas and 79% (31/39) of these were missed on CXR. 7% (3/42) were epidermoid carcinomas or small cell carcinomas and 66% (2/3) of these were missed on CXR. The overall accuracy of interpretation on CXR for lung cancers was 61%, sensitivity was 23% and specificity 96%. Although there was an association between presence of lung cancer and positive reading of CXR (chi 2 test of association, p < 0.05), the percentage of positive readings was only 23%. Thus, CXR was poor at visualizing CT detectable lung cancers of < or = 20 mm diameter, which are usually of very low density, and cannot be relied upon for detection of surgically curable small lung cancer.

Adenocarcinoma↗

PubMed2000

Rapidly growing small peripheral lung cancers detected by screening CT: correlation between radiological appearance and pathological features.

12 peripheral small lung cancers (< 20 mm) of rapid growth (volume doubling time < 150 days), detected by repeated low dose CT screening, were evaluated to examine their CT features and to correlate such features with histopathological findings. Each patient's CT images, including follow-up and thin section CT images, were studied retrospectively to determine tumour growth rate and CT morphological features. Nine of the tumours exhibited a solid tumour growth pattern: seven of these showed a well defined, homogeneous, soft tissue density with spicular or lobulated margin. These seven tumours included small cell lung cancer (n = 3), moderately differentiated adenocarcinoma (n = 2), poorly differentiated adenocarcinoma (n = 1) and squamous cell carcinoma (n = 1). The other two tumours, a moderately differentiated adenocarcinoma and a well differentiated adenocarcinoma, appeared as irregular, soft tissue density nodules with poorly defined margins. The latter exhibited an air bronchogram pattern and a small cavity. The remaining three tumours exhibited a lepidic tumour growth pattern. They showed ground glass opacity or ground glass opacity with a higher density central zone on CT images and were well differentiated adenocarcinomas. In conclusion, most peripheral small lung cancers of rapid growth were adenocarcinomas. They also included small cell lung cancer and squamous cell carcinoma. The majority showed solid tumour growth pattern and lacked an air bronchogram and/or small air spaces in the nodule. Some well differentiated adenocarcinomas with lepidic tumour growth pattern also showed rapid growth.

Adenocarcinoma↗

PubMed2000

Growth rate of small lung cancers detected on mass CT screening.

CT has recently been used in mass screening for lung cancer. Small cancers have been identified but the growth characteristics of these lesions are not fully understood. We identified 82 primary cancers in our 3-year mass CT screening programme, of which 61 were examined in the present study. The volume doubling time (VDT) was calculated based on the exponential model using successive annual CT images or follow-up CT images. All cases were also examined in the hospital by high resolution CT (HRCT). Lesions were divided into three types based on HRCT characteristics: type G (n = 19), ground glass opacity (GGO); type GS (n = 19), focal GGO with a solid central component; and type S (n = 23), solid nodule. 18 (95%) lesions of type G, 18 (95%) of type GS and 7 (30%) of type S were invisible on conventional chest radiographs. The mean size of the tumour was 10 mm, 11 mm and 16 mm for type G, type GS and type S, respectively. Most tumours (80%) were adenocarcinomas; 78% of these were GGO (type G and GS). Mean VDT values were 813 days, 457 days and 149 days for type G, type GS and type S, respectively; these are significantly different from each other (p < 0.05). Our results show that annual mass screening CT for 3 successive years resulted in the identification of a large number of slowly growing adenocarcinomas that were not visible on chest radiographs.

Adenocarcinoma↗

PubMed2000

Cellular mechanisms of cardioprotection afforded by inhibitors of angiotensin converting enzyme in ischemic hearts: role of bradykinin and nitric oxide.

Angiotensin converting enzyme (ACE) inhibitors inhibit the degradation of bradykinin and contribute to accumulation of bradykinin and NO, both of which may be beneficial for diseased hearts. To test this idea, we administered imidaprilat and cilazaprilat, respectively to the canine ischemic myocardium. In the open chest dogs with low constant coronary perfusion pressure (CPP, from 104 +/- 3 to 42 +/- 3 mmHg), coronary blood flow (CBF, 91 +/- 1 to 32 +/- 2 ml/100 g/min), fractional shortening (FS), and lactate extraction ratio (LER) decreased. Either imidaprilat or cilazaprilat increased CBF, FS, and LER with increases in cardiac bradykinin and NO levels. The beneficial effects of ACE inhibitors were blunted by either L-NAME (an inhibitor of NO synthase) and HOE140 (an inhibitor of bradykinin receptors), respectively. ACE inhibitors, on the other hand, are reported to attenuate the severity of myocardial stunning, which effect is partially attributable to bradykinin- and NO-dependent mechanisms. Further, ACE inhibitors limited infarct size following coronary occlusion and reperfusion. This infarct size-limitation was blunted by either L-NAME and IBTX (the antagonist of K(Ca) channels). Bradykinin is also reported to close K(Ca) channels. Thus, we concluded that ACE inhibitors attenuate both reversible and irreversible myocardial cellular injury via bradykinin/NO-dependent mechanisms. In experimental and clinical settings, the cardioprotective effects of ACE inhibitors on the diseased heart may be attributable to these mechanisms.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

[Cancer chemotherapy based on evidence--metastatic breast cancer].

Breast cancer is relatively sensitive to chemotherapy. However, although response rate to chemotherapy is reported to be from 50 to 70% in metastatic breast cancer, it is incurable. Current standard chemotherapeutic regimens do not provide a large survival benefit according to the evidence obtained from clinical studies. Before developing a treatment program, we should therefore realize that the aims of chemotherapy for metastatic breast cancer are improvement of quality of life through relief of symptoms, and prolonging survival.

Aged↗

PubMed2000

[Interim report on JFMTC Study no. 21 on the effectiveness of UFT as an adjuvant therapy for semi-advanced cancer of the stomach].

This interim report, for findings as of May, 1998, covers data on 435 gastrectomized patients with semi-advanced stomach cancer collected from 144 institutions between November, 1993 and March, 1996. The active arm of the study involved CDDP i.p. administration of 70 mg/m2 at the time of resective surgery, followed by UFT oral administration for one year at 3-4 capsules daily. A randomized control involved no adjuvant therapy after CDDP i.p. administered as in the active arm. The results obtained indicated no significant difference between the groups in terms of 3 year survival or disease free survival rates. Reports appearing elsewhere have suggested that 3-4 capsules/day of UFT may be insufficient to reach the threshold of the effective tissue level, and that 6 capsules may be necessary to obtain the expected results. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

[Giant osteoma of the temporal bone with otitis media: a case study].

A 71-year-old female presented with a giant osteoma of the right temporal bone and otitis media. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the giant osteoma. An operation was performed to alleviate the difficult-to-treat otitis media and to address the related cosmetic problem. During the operation, three-dimensional CT (3D-CT) was very helpful in understanding the relationship between the tumor and the peripheral structures. Removal of the tumor improved the patient's otitis media. Osteoma of the temporal bone is rare. Only twenty-one cases of mastoid osteoma have been reported in Japan. In the present study, we review osteomas of the temporal bone and discuss their management.

Aged↗

PubMed2000

[Interim report of JFMTC study no. 20 on the effectiveness of high dose CDDP plus 5-FU regimen as an adjuvant therapy for far-advanced cancer of the stomach].

This interim analysis of the JFMTC study as of May, 1998 covers 321 gastrectomized patients with far-advanced stomach cancer from 135 institutions between November, 1993 and March, 1996. The intensive therapy group (I-group) received CDDP i.p. administration on resective surgery with 70 mg/m2 followed by CDDP i.v. of 80 mg/m2 (day 1, i.v.), accompanying 5-FU of 350 mg/m2/day (day 1-5, c.v.i.) in the 4th, 8th and 12th weeks. The I-group was randomly compared with the standard therapy group (S-group) of MMC of 6 mg/m2 i.v. in the 4th, 8th and 12th weeks and UFT of 3-4 capsules daily for postoperative one year. The results obtained were that 1. adverse reactions were found more in the I-group than in the S-group, particularly notable in the decrease in blood cells, loss of appetite and nausea/vomiting, and incidence of grade 3 or more being 13% (neutrophile leukocytes), 26% and 21%, respectively; 2. there was no significant difference between I- and S-groups in terms of 3-year survival or disease-free survival rates. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

Antineoplastic Combined Chemotherapy Protocols↗