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Biomedical subjects

T Tashiro

Publications and source records attributed to T Tashiro.

At least 163 records · Page 9Linked to original sources

[Effects of insulin-like growth factor-I in burned rats].

Effect of insulin-like growth factor-I (IGF-I) on protein metabolism was investigated in burned rats receiving TPN. Twenty-six male SD rats were divided into two groups. IGF-I was administered to group IGF (IGF-I group, n = 14), but not to group C (Control group, n = 12). Loss of body weight after burn in group IGF was significantly lower than group C (p < 0.01). Cumulative nitrogen balance for 2 postburn days in group IGF was significantly higher than group C (p < 0.01). Rate of whole body protein turnover, synthesis and breakdown increased significantly in group IGF compared with group C. On the other hand, blood glucose was decreased significantly in group IGF (p < 0.05). Water balance made no significant difference between two groups. In group IGF, weight of the spleen, kidney, small intestine and colon increased significantly. Fractional synthesis rate and protein content of mucosa of the small intestine were significantly higher in group IGF than group C. From the histological point of view, mucosal layer was thickened and hyperplastic. Catabolism and surgical diabetes are caused in the surgical stress, and the administration of IGF-I are thought to be effective for improvement of those conditions. And IGF-I has the most remarkable effect on the small intestine of all organs studied in our experiment.

Animals↗

Construction of a novel bifunctional biogenic amine receptor by two point mutations of the H2-histamine receptor.

BACKGROUND: H2-histamine receptors mediate a wide range of physiological functions extending from stimulation of gastric acid secretion to induction of human promyelocyte differentiation. We have previously cloned the H2-histamine receptor gene and noted that only three amino acids on the receptor were sufficient to define its specificity and selectivity. Despite only modest overall amino acid homology (34% amino acid identity and 57.5% similarity) between the H2-histamine receptor and the receptor for another monoamine, the beta 2-adrenergic receptor, there is remarkable similarity at their critical ligand binding sites. We hypothesized that, if the specificity and selectivity of both receptors are invested in just three amino acids, it should be possible to convert one of the receptors into one that recognizes the ligand of the other by simple mutations at only one or two sites. MATERIAL AND METHODS: We explored the effect of two single mutations in the fifth transmembrane domain of the H2-histamine receptor, which encompasses the sites that determine H2 selectivity. The canine H2 receptor gene was mutated at Asp186 and Gly187 (Asp186 to Ala186 and Gly187 to Ser187) by oligonuceotide directed mutagenesis. The coding region of both the wild-type and mutated H2 receptors was subcloned into the eukaryotic expression vector, CMVneo, and stably transfected into Hepa cells and L cells. The biological activity of histamine and epinephrine on the expressed receptor was examined by measurement of cellular cAMP production and inositol trisphosphate formation. RESULTS: Hepa cells transfected with the Ala186-Ser187 mutant H2 receptor demonstrated a biphasic rise in cAMP in response to epinephrine with an early phase (ED50 approximately 10(-11) M) that could be inhibited by both propranolol and cimetidine. Epinephrine also induced IP3 generation in the same cells, a biological response that is characteristic of activation of the wild-type H2 but not of the beta-adrenergic receptor. L cells transfected with the Ala186-Ser187 mutant H2 receptor also responded to epinephrine in a cimetidine and propranolol inhibitable manner. CONCLUSIONS: We converted the H2-histamine receptor into a bifunctional one that has characteristics of both histamine and adrenergic receptors by two simple mutations. These results support the hypothesis that ligand specificity is determined by only a few key points on a receptor regardless of the structure of the remainder of the molecule. Our studies have important implications on the design of pharmacological agents targeted for action at physiological receptors.

Adrenergic beta-Antagonists↗

Intradural chordoma: case report and review of the literature.

Chordomas are rare neoplasms arising from notochordal remnants found predominantly in the clivus and the sacrococcygeal regions. Most clivus chordomas show extradural extension and bone destruction. Such a tumour can rarely be intradural. This report is concerned with the radiological findings in prepontine intradural chordoma.

Brain Neoplasms↗

Antitumor effects of IST-622, a novel synthetic derivative of chartreusin, against murine and human tumor lines following oral administration.

The antitumor effects of 6-O-(3-ethoxypropionyl)-3',4'-O-exo- benzylidenechartreusin (IST-622), a new synthetic derivative of chartreusin (CT), were investigated. Following oral administration, IST-622 showed marked antitumor effects against various mouse tumors such as P388 and L1210 leukemias, B16 melanoma, Lewis lung carcinoma, Colon 26 and Colon 38 adenocarcinomas, and M5076 reticulum-cell sarcoma. The best antitumor effects were obtained by five intermittent treatments given every 4 days. In addition, IST-622 showed a significant growth-inhibitory effect against two human tumor xenografts, a large-cell lung cancer (Lu-116) and a gastric adenocarcinoma (St-4), among the seven lines tested. IST-622, which was rapidly metabolized into 3',4'-O-exo-benzylidenechartreusin (A-132) and not into CT in vivo or in culture medium, exhibited remarkable growth-inhibitory activity against P388 leukemia in vitro, its 50% growth-inhibitory concentration (IC50) being over 20-fold lower than that of CT. IST-622 showed an in vivo antitumor effect superior to that of authentic A-132, possibly resulting from a higher absorption ratio of IST-622 through the gastrointestinal tract. IST-622 is now under clinical phase I study in Japan.

Administration, Oral↗

Disseminated Trichosporon beigelii infection in patients with malignant diseases: immunohistochemical study and review.

Trichosporon beigelii is a causative agent of opportunistic infection and summer-type hypersensitivity pneumonitis in Japan. However, as the diagnosis of Trichosporon beigelii infection is sometimes difficult, the actual incidence of this disease may be underestimated. Of 203 autopsy patients with malignant disease, seven (7.7%) were diagnosed with disseminated Trichosporon beigelii infection by immunohistochemical investigation of formalin-fixed, paraffin-embedded tissue sections. Including these seven, a total of 43 patients with Trichosporon beigelii infection have been reported in Japan. The majority of them had underlying hematologic malignancies, for which they received cytotoxic chemotherapy resulting in neutropenia. This study indicates that the immunohistochemical method, which can be applied to biopsy specimens, is an excellent tool for specific diagnosis of Trichosporon beigelii infection, which is an emerging fatal mycosis in immunocompromised patients with profound neutropenia.

Aged↗

Axonal transport of actin and actin-binding proteins in the rat sciatic nerve.

Actin is one of the major cytoskeletal proteins carried in slow axonal transport. Since more than 50% of actin in the axon was recovered in the high-speed supernatant, we looked for G-actin-binding proteins in slow axonal transport. Two weeks after injection of L-[35S]methionine into the rat spinal cord (L3-L5), labeled proteins in the sciatic nerve were extracted and those with potential abilities to interact with G-actin were detected by two independent methods: (A) DNAase I affinity chromatography and (B) blot overlay with biotinylated actin. By method (A), a 68 kDa Ca(2+)-dependent binding protein and a 45 kDa Ca(2+)-independent binding protein were detected. The 68 kDa protein was also a major protein binding to actin in method (B). The 68 kDa protein was identified with the Ca(2+)-dependent phospholipid binding protein annexin VI by two-dimensional electrophoresis and Western blotting. As annexin VI is a component of slow axonal transport, it does not seem to be bound to membranous organelles in the axon. Our results suggest that annexin VI may play a role in the control of actin assembly and membrane-microfilament interaction.

Actins↗

Aetiology of maxillofacial fracture.

The aetiological factors associated with maxillofacial fractures, and the trends in these factors over a 13 year period are reported. The First Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokyo Medical and Dental University, managed 695 patients with maxillofacial fractures between 1977 and 1989. The male to female ratio was 3.2:1 and the majority of patients were aged between 10 and 30 years old. Road traffic accidents and accidental falls were the main causes of fractures throughout the 13 year study period. Mandibular fractures occurred in 477 patients (68.6%). A high percentage of patients were treated by closed reduction and maxillo-mandibular fixation, or occlusal splinting.

Accidental Falls↗

Early effects of beta,beta'-iminodipropionitrile on tubulin solubility and neurofilament phosphorylation in the axon.

To elucidate the role of neurofilaments in microtubule stabilization in the axon, we studied the effects of beta,beta'-iminodipropionitrile (IDPN) on the solubility and transport of tubulin as well as neurofilament phosphorylation in the motor fibers of the rat sciatic nerve. IDPN is known to impair the axonal transport of neurofilaments, causing accumulation of neurofilaments in the proximal axon and segregation of neurofilaments to the peripheral axoplasm throughout the nerve. Administration of IDPN at various intervals after radioactive labeling of the spinal cord with L-[35S]methionine revealed that transport inhibition occurred all along the nerve within 1-2 days. Transport of cold-insoluble tubulin, which accounts for 50% of axonal tubulin, was also affected. A significant increase in the proportion of cold-soluble tubulin was observed, reaching a maximum at 3 days after IDPN treatment and returning to the control level in the following weeks. Preceding this change in tubulin solubility, a transient decrease in the phosphorylation level of the 200-kDa neurofilament protein was detected in the ventral root using phosphorylation-dependent antibodies. These early changes agreed in timing with the onset of segregation and transport inhibition, suggesting that interaction between neurofilaments and microtubules possibly regulated by phosphorylation plays a significant role in microtubule stabilization.

Actin Cytoskeleton↗

Evaluation of antitumor activity of navelbine (vinorelbine ditartrate) against human breast carcinoma xenografts based on its pharmacokinetics in nude mice.

The in vitro antitumor activity of navelbine (NVB, KW-2307), a newly synthesized vinca alkaloid, was compared with that of adriamycin (ADM) against human breast carcinomas inoculated into nude mice at the maximum tolerated dose (MTD) and clinically equivalent dose (CED). The plasma levels of NVB after intravenous injection into nude mice at doses of 1.2 and 4.8 mg/kg diminished rapidly during the early phase (0-1 h), followed by a very long shallow one. NVB was still detected 96 h after administration at a dose of 4.8 mg/kg. The pharmacokinetic parameters of NVB in plasma indicated that NVB extensively distributes to tissues. The CED of NVB was provisionally decided to be 4.8 mg/kg based on the comparison of AUC values at 24-infinity h between human patients and nude mice. When compared by a single injection of MTD (NVB, 16 mg/kg; ADM 12 mg/kg), NVB was effective against all four tumor lines, MC-2, MC-8, MMKY and H-31, while ADM was effective only against H-31. On the other hand, the body weight loss by NVB was mild as compared with that by ADM, indicating that the antitumor activity of NVB is superior to that of ADM at their MTDs. A single injection of NVB at its CED (4.8 mg/kg) produced a poor antitumor effect and no or little toxicity in terms of body weight loss, as compared with those at MTD. However, when NVB was administered intermittently at CED, it exhibited significant antitumor activity against three tumor lines. The body weight loss was still mild even on this intermittent schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Papillary↗

Extended endocardial repair of postinfarction ventricular septal rupture: new operative technique--modification of the Komeda-David operation.

Between January 1992 and November 1992, four consecutive patients (ages 53 to 81 years) underwent early surgical repair of postinfarction ventricular septal ruptures using a new simple operative technique. The principles of the technique are longitudinal incision of the infarcted left anterior ventricular wall, placement of a saccular patch of single equine pericardium that covers the infarcted left ventricular wall, and large buttressed suture closure of the left ventriculotomy. The infarcted septum and infarcted left ventricular wall are completely separated from the left ventricular cavity. In this procedure, the infarcted myocardium is not resected, and left and right ventricular muscles are preserved. This technique is simple and safe for use in the acute phase of myocardial infarction, and it preserves ventricular function after surgery.

Aged↗

Impairment of cytoskeletal protein transport due to aging or beta,beta'-iminodipropionitrile intoxication in the rat sciatic nerve.

Three major age-related changes in cytoskeletal organization and metabolism in the axon were observed by comparing slow axonal transport in the sciatic nerves of rats aged 7-80 weeks: (a) a progressive decrease in the rate of slow axonal transport, (b) a tight association of cold-insoluble tubulin with the neurofilament (NF) proteins and (c) an accelerated proteolysis of the severely retarded proteins, especially NF proteins. These changes were reproduced to a large extent in the young animal by intoxication with beta,beta'-iminodipropionitrile (IDPN). As IDPN is known to impair the axonal transport of NF proteins and cause segregation of NFs from microtubules, the results indicate that NF-microtubule interaction is one of the major factors regulating the axonal cytoskeleton. The importance of the balance between transport rate and degradation rate in the maintenance of the normal axonal cytoskeleton is stressed especially in the aged animal.

Actins↗

[Problems concerned with adult T-cell leukemia. 1) Causes of death and early diagnosis of cytomegalovirus pneumonia in adult T-cell leukemia. 2) Clinicopathological features of CD30 positive adult T-cell leukemia].

1) We studied the causes of death confirmed by autopsy or necropsy in 23 adult T-cell leukemia (ATL) patients. Of them eight showed involvement of tumor (35%), eleven infectious disease (47%) (nine cytomegalovirus (CMV) pneumonia, one varicella-zostervirus pneumonia, one pseudomonas aeruginosa pneumonia), and four others (17%). In seven recent cases treated with a new chemotherapy regimen in combination with G-CSF administration, survival was longer than in previous cases and tumor involvement as a cause of death decreased (one case, 14%). However, CMV pneumonia inclined to increase (six cases, 86%). Therefore, we tried to retrospectively detect CMV DNA in the serum of ATL patients using a nested polymerase chain reaction (PCR). CMV pneumonia was reliably diagnosed in eleven ATL patients, whereas CMV DNA was detected in all patients at the time of clinical onset of pneumonia and CMV DNA was detected only in eight patients from 7-35 days before the onset of pneumonia. These findings suggest that the nested PCR assay is a useful tool to early diagnosis CMV pneumonia in ATL patients. 2) Recently, several cases of ATL with CD30 antigen have been reported, but its clinical relevance remains unknown. Accordingly, we studied CD30 antigen expression in 36 ATL patients who had monoclonal integration of HTLV-I provirus in the tumor cells and demonstrated the immunohistochemical and clinical characteristics of these patients. CD30 antigen expression was evident in seven of these 36 patients (19.4%). A comparison of ATL cases with and without CD30 antigen expression revealed significantly large numbers of abnormal lymphocytes in the peripheral blood and lower serum calcium levels in CD30 antigen positive ATL.

Adult↗

[Enhanced anti-tumor effect of lymphokine-activated killer cells transfected with tumor necrosis factor-alpha gene on human glioma cells].

Tumor necrosis factor (TNF)-alpha gene were transfected into lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 by means of novel liposomes with a positive charge on their surface. The cells secreted significant amounts of TNF-alpha into the culture medium and exhibited reinforcement of cytotoxicity toward a human glioma cell line (U251-SP), being three times more cytotoxic than nontransfected LAK cells. The mechanism for the reinforcement of cytotoxicity is considered to involve not only an increase in TNF-alpha secretion from LAK cells but also its expression on their surface. Intratumoral or intrathecal injection of LAK cells transfected with the TNF-alpha gene may be useful for the treatment of patients with malignant glioma.

Genes, Tumor Suppressor↗

[A case of malignant hemangiopericytoma arising from the mediastinum accompanied by hepatocellular carcinoma].

A 65-year-old man was admitted to Oita Medical University Hospital with complaints of right back pain, diplopia and vertigo. A tumor, 33 x 25 mm, was found on the right lateral chest wall on admission. Chest X-ray film and chest CT scan showed a tumor, 50 x 30 mm, in the right posterior mediastinum. The chest wall tumor was diagnosed as malignant hemangiopericytoma by biopsy, and the same diagnosis was made for the mediastinal lesion by aspiration cytology. Brain MRI showed a mass at the skull base, which was found to be a metastatic bone tumor from the mediastinal malignant hemangiopericytoma. Abdominal CT scan showed a massive tumor, 65 x 60 mm, in the right lobe of the liver. The liver tumor was diagnosed as hepatocellular carcinoma by biopsy. Combination chemotherapy, employing cyclophosphamide, vincristine, pirarubicin and dacarbazine (DYVADIC), in conjunction with radiation therapy, produced no response. The patient died 5 months after admission. Malignant hemangiopericytoma arising from the mediastinum is uncommon. Thus, the clinical features of our case, as well as those of previously reported cases in Japan, are discussed herein.

Aged↗