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Biomedical subjects

I Takahashi

Publications and source records attributed to I Takahashi.

At least 19 recordsLinked to original sources
PubMed1992

Hyperthermia enhances the inhibition of tumor growth by 1-(2-tetrahydrofuryl)-5-fluorouracil/uracil (1:4) in tumors in mice and humans.

The cytotoxicity of several antitumor drugs is enhanced by hyperthermia (HT). Using mouse Sarcoma-180 (S-180) tumors, the authors examined the effects of 5-fluorouracil (5-FU) and a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and uracil in a molar ratio of 1:4 (UFT), in combination with HT. The antitumor effect of 5-FU was not enhanced significantly by HT. Growth inhibition by UFT plus HT was significantly greater than that by UFT alone, whereas inhibition by UFT alone was significantly greater than that by 5-FU. The intracellular metabolism of 5-FU and FT in whole homogenates of S-180 cells, human tumor cell lines (SC-2 and Lu-99), and five fresh human tumor tissues also was investigated. Conversion of FT to 5-FU, phosphorylation, and degradation of 5-FU were assayed with [3H]FT or [3H]5-FU, and the products were separated by thin-layer chromatography. The conversion of FT to 5-FU and the phosphorylation of 5-FU were more rapid at 43 degrees C than at 37 degrees C, whereas the degradation of 5-FU to 2-fluoro-beta-alanine remained unchanged. This acceleration of the active metabolism of FT and 5-FU may be one explanation for the enhanced effect of UFT by HT.

Animals↗
PubMed1992

Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease.

Type IIA von Willebrand disease (vWD) is the most common type II vWD and is characterized by the selective loss of large and intermediate sized multimers. One explanation for this disorder has been postulated to be a qualitative defect in von Willebrand factor (vWF) which results in increased susceptibility to proteolysis at the bond between residues Tyr842 and Met843. Four missense mutations that may cause type IIA vWD have recently been identified near the cleavage site. We analyzed the molecular basis for type IIA vWD in six patients. A 512 bp DNA sequence spanning the proteolytic cleavage site was targeted for PCR amplification and sequencing. We exploited a difference in restriction sites between the vWF gene and the pseudogene and have designed allele-specific oligomer used with PCR to distinguish these two genes. Three candidate missense mutations; Ser743 (TCG)----Leu (TTG), Leu799 (CTG)----Pro (CCG), and Arg834 (CGG)----Trp (TGG) were identified in 4 out of 6 patients. The amino acid substitution at Arg834 has been reported previously, but the other substitutions at Ser743 and Leu799 are novel candidate mutations locating 99 and 43 amino acids to the N-terminal side of the cleavage site, respectively. Our results indicate that amino acid substitutions located relatively distant from the cleavage site may also be involved in type IIA vWD.

Base Sequence↗
PubMed1992

Wortmannin, a microbial product inhibitor of myosin light chain kinase.

We have found that a fungal strain, Talaromyces wortmannin KY12420, produces a potent inhibitor of smooth muscle myosin light chain kinase (MLCK). This active product, designated as MS-54, was isolated and purified from the culture broth of the fungus and identified as wortmannin. The inhibition of MLCK by wortmannin was prevented by a high concentration of ATP. The activity of the catalytic domain, which was disclosed by partial tryptic digestion, was also inhibited by wortmannin. These results suggest that wortmannin acts at or near to the catalytic site of the enzyme. It was shown clearly by kinetic analyses, preincubation studies, and dialysis experiments that the inhibitory action of wortmannin on MLCK was irreversible. Under the condition of preincubation for 3 min, 0.3 microM wortmannin inhibited the activity of MLCK, while 10 microM wortmannin had no effect on the activities of cAMP-dependent protein kinase, cGMP-dependent protein kinase, and calmodulin-dependent protein kinase II, and had little effect on protein kinase C activity. These data expressed clearly the marked selectivity of the compound for MLCK. Furthermore, wortmannin also inhibited both the phosphorylation of myosin light chain and the contraction in rat thoracic aorta stimulated with KCl, which indicates the effectiveness of the compound in the cellular level as an MLCK inhibitor.

Adenosine Triphosphate↗
PubMed1992

A female hemophilia A combined with hereditary coagulation factor XII deficiency: a case report.

A 2-year-old Japanese girl with easy bruising and arthropathy was demonstrated to have severe hemophilia A (Factor VIII activity: less than 0.01 U/ml). She had normal 46XX karyotype. Her brother also had hemophilia A, and her mother and grandmother seem to be hemophiliac carriers. Additionally, activated partial thromboplastin time (APTT) of the patient was disproportionately prolonged and there were reduced levels of coagulation factor XII in the patients and members of the maternal trait which are compatible with heterozygous factor XII deficiency. Her father had both normal factor VIII and factor XII levels. Southern blotting analysis of genomic DNA from the propositus and family members with factor VIII and factor XII DNA probes revealed no gross alterations. This patient represents a female hemophilia A combined with heterozygous factor XII deficiency. Nonrandom inactivation of a normal X-chromosome (extreme lyonization) may be the basis for the expression of hemophilia A in this female patient.

Blood Coagulation↗
PubMed1992

Primary malignant tumors of the small intestine: analysis of 40 Japanese patients.

Forty Japanese patients with primary malignant tumors of the small intestine were reviewed. Adenocarcinoma was the most common tumor type comprising 19 patients (47%), followed by malignant lymphoma, 11 (30%), leiomyosarcoma, 8 (20%) and carcinoid tumor, 1 (3%). Adenocarcinomas and leiomyosarcomas were primarily located in the duodenum or jejunum, whereas lymphomas were more common in the jejunum or ileum. Abdominal pain (65%) and nausea or vomiting (35%) were the most common symptoms with these tumors. Barium contrast studies were able to detect 83% of these tumors. Our results also suggest that computed tomography and ultrasonography are not reliable for diagnosing jejunal tumors while superior mesenteric angiography is effective for diagnosing ileal tumors. The duodenal and ileal tumors tended to metastasize to lymph nodes while jejunal ones tended to penetrate the serosa or to disseminate into the peritoneal cavity. The percentage of tumors potentially cured by surgery and the 5 year survival rates of the leiomyosarcomas (75% and 57%, respectively) were higher than those of adenocarcinomas (42% and 10%, respectively) and lymphomas (42% and 32%, respectively).

Adenocarcinoma↗
PubMed1992

Noncurative resection for advanced gastric cancer.

Between 1965 and 1985, 489 patients with advanced gastric cancer who were treated with gastric resection and in whom tumor cells remained after the operation were defined as cases of a "noncurative resection." The clinicopathological features and prognosis of these patients were examined and two groups were prepared: locally advanced cancer and cancer with a distant metastasis. In locally advanced cancer cases, tumor cells remained in the neighboring organs, lymph nodes, and/or resected margins; in those with distant metastasis, peritoneal dissemination and/or liver metastasis were present regardless of whether or not the metastasis was removed, with or without locally noncurative factors. Serosal invasion was prominent and high rates of lymph node metastasis and lymphatic involvement were evident in both groups. The survival rate for patients with locally advanced gastric cancer was better than that of patients with distant metastasis (P < 0.01). Survival time in patients with locally advanced cancer can be lengthened by resecting all of the primary tumor and as much of the metastatic lesions as possible, even if the surgical management is "noncurative." Aggressive postoperative chemotherapy for patients with distant metastasis from a gastric cancer is to be recommended.

Aged↗
PubMed1992

Palliative radiotherapy of bone metastasis.

We analyzed the effects of radiotherapy on 226 sites of metastatic bone tumors from 1981 to 1984, and on 157 sites of bone metastases of prostate cancer from 1970 to 1988. The radiation effect on pain relief was recognized in about 90% of cases within the dose of 20Gy to 30Gy, and there were not many differences in these effects according to the original tumors or histological types. In prostate cancer, the sites which needed re-irradiation were not recognized within 6 months after irradiation, and only 12 out of 80 sites (15%) that could be observed after more than 6 months needed re-irradiation due to recurring pain. As more than 60% of the patients with prostate cancer who needed irradiation to control bone metastases died within a year, to get pain relief by irradiation immediately and safely was thought to be very useful from the viewpoint of useful life. One patient was irradiated on 16 sites and 2 of these 16 sites received 4 treatments of irradiation and the shortest interval was 10 months and the longest one was 18 months.

Bone Neoplasms↗
PubMed1992

5-Fluorouracil's cytotoxicity is enhanced both in vitro and in vivo by concomitant treatment with hyperthermia and dipyridamole.

We obtained evidence that the cytotoxic effect of 5-fluorouracil (5-FU) is augmented when the drug is given in combination with hyperthermia (HYP) and dipyridamole (DP). Nontoxic levels of DP enhanced the combined cytotoxicity of 5-FU and HYP against B16 melanoma and human tumor cells in vitro as measured by the succinate dehydrogenase inhibition (SDI) test. Growth of B16 melanoma that had been subcutaneously implanted into the feet of C57 BL mice was inhibited by treatment with the combinations of 5-FU and HYP, of 5-FU and DP, and of 5-FU, HYP and DP as compared with the administration of 5-FU alone. Treatment with HYP plus DP did not alter the body weight of mice that received 5-FU. The administration of DP plus HYP seemed to render the tumor cells more sensitive to 5-FU. The combination of 5-FU, HYP and DP shows promise for the treatment of patients suffering from malignant disease.

Animals↗
PubMed1992

A case of tubulo-interstitial nephritis with exfoliative dermatitis and hepatitis due to phenobarbital hypersensitivity.

Severe exfoliative dermatitis and liver dysfunction developed in a 5-year-old girl 3 weeks after initiation of phenobarbital therapy. Liver function improved gradually after discontinuation of phenobarbital. During the convalescent stage an initially mild renal dysfunction was exacerbated by episodes of post-transfusion haemolysis. Liver biopsy revealed moderate parenchymal damage with subacute cellular infiltration. Renal biopsy demonstrated the cardinal findings of interstitial nephritis, excluding the possibility of acute tubular necrosis caused by haemolysis. Serial lymphocyte transformation studies and skin patch tests gave positive results for phenobarbital, supporting the view that these were unusual complications of phenobarbital hypersensitivity.

Chemical and Drug Induced Liver Injury↗
PubMed1992

Postoperative chemotherapy for patients with advanced gastric cancer.

The relationship between postoperative chemotherapy and survival time after gastric resection in patients with advanced gastric cancer was examined by retrospectively reviewing data on 916 patients treated in our clinics between 1965 and 1985. Of these patients, 738 were treated postoperatively with antitumor drugs. Postoperative chemotherapy was more often prescribed for those in the advanced stages of malignancy. Univariate analysis revealed that the survival time of patients given postoperative chemotherapy was shorter than for those not receiving chemotherapy, but there was no statistical significance. Multivariate analysis using the Cox regression analysis adjusted for sex, age, and other covariants indicated that operative curability, liver metastasis, serosal invasion, lymph node metastasis, peritoneal dissemination, and tumor size were the important prognostic factors. There was no correlation with postoperative chemotherapy. Our findings rule out any relationship between postoperative chemotherapy and length of survival time for patients with advanced gastric cancer undergoing gastric resection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Relationship between tumor histopathology and in vitro sensitivity to antitumor drugs in gastric cancer.

The in vitro drug sensitivity of gastric cancer tissues obtained from 40 patients with advanced cancer was compared in terms of the pathological classifications which were assigned according to the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan. Cases of poorly differentiated adenocarcinoma which had penetrated the serosa were evaluated using the succinate dehydrogenase inhibition (SDI) test for determining the in vitro chemosensitivity. The sensitivity of the stage III group to cisplatin was higher than that of the stage IV group. Although there were no statistical differences in drug sensitivities according to macroscopic findings (Borrmann's classification), the expanding growth type was more susceptible that the infiltrating type to cisplatin, aclacinomycin A (ACR) and carboquone (CQ) microscopically. In cases of lymph node metastasis [n(+)] the sensitivity to cisplatin, ACR, CQ, adriamycin and mitomycin C was less than in those with or without primary lymph node metastasis [n(-)]; lymphatic invasion in the gastric wall (ly) was a significant factor linked to drug resistance. Our findings indicate that the evaluation of tumor pathology is important in predicting the chemosensitivity of poorly differentiated gastric cancers.

Aclarubicin↗
PubMed1992

Metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in partially hepatectomized rats.

Changes in the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in the plasma, lung, liver, stomach, small intestine, spleen and kidney in two-thirds partially hepatectomized rats. Concentrations of tegafur and 5-FU in plasma and tissues were determined 30 min after injecting 100 mg/kg of tegafur via the tail vein. The 5-FU concentration in the plasma remained unchanged for the first 7 days after hepatectomy. The tissue level of 5-FU was higher in the liver and kidney than in other organs examined, but there were no changes in levels of 5-FU in each organ examined. Our observations support the proposal that the conversion of tegafur to 5-FU is maintained in partially hepatectomized rats.

Animals↗
PubMed1992

Genetic control of immune responses in mice to synthetic peptides of a Streptococcus mutans surface protein antigen.

The immune responses to a cell surface protein antigen (PAc) of Streptococcus mutans and a peptide corresponding to residues 301 to 319 of the protein antigen [PAc(301-319)] in various strains of mice were studied, with attention being given to the haplotype of major histocompatibility complex (MHC) class II genes. Subcutaneous immunization of mice carrying the MHC class II I-Ad gene [BALB/c, B10.D2, B10.GD, and (B10.D2 x B10.G)F1 mice] with the peptide induced strong serum immunoglobulin G (IgG) responses to recombinant PAc (rPAc) and the peptide. Subcutaneous immunization of mice carrying the haplotype k or b of the H-2 I-A gene (C3H/HeN, C57BL/6, B10.BR, B10.A, or B10 mice) with the peptide induced intermediate serum IgG responses to rPAc and the peptide, and subcutaneous immunization of mice carrying the haplotype s or q of the H-2 I-A gene (DBA/1, B10.S, or B10.G mice) induced weak serum IgG responses to rPAc and the peptide compared with the responses of mice carrying the I-Ad gene. PAc(301-319) strongly induced PAc(301-319)-specific T-cell proliferation in B10.D2 mice but not in B10.G mice. The T-cell proliferation in B10.D2 mice was inhibited by treatment of antigen-presenting cells with anti-I-Ad monoclonal antibody but not with anti-I-Ab monoclonal antibody. These results indicate that the immune responses to the peptide in mice are genetically restricted or dominated by the MHC class II gene (I-Ad). To map antigenic epitopes in PAc(301-319) and PAc in mice bearing different H-2 haplotypes, 10 overlapping decapeptides covering PAc(301-319) and 153 decapeptides covering the entire mature PAc were synthesized. Of 10 decapeptides covering PAc(301-319), 6, 7, 1, and 1 decapeptides showed strong reactions with anti-PAc(301-319) sera from B10.D2 (H-2d), B10.GD (H-2g2), B10.BR (H-2k), and B10.A (H-2a) mice, respectively. None of these overlapping decapeptides reacted with anti-PAc(301-319) sera from B10.S (H-2s) and B10.G (H-2q) mice. Epitope-scanning analyses of the mature PAc molecule showed that antigenic epitopes scattered throughout the molecule and that antigenic epitope patterns differed in mice with different H-2 haplotypes. In addition, there was little overlap of immunogenic peptides among the mice with different haplotypes.

Amino Acid Sequence↗
PubMed1992

A comparison of the immunohistochemical localization of type I and type II collagens in craniofacial cartilages of the rat.

The immunohistochemical localization of types I and II collagen was examined in the following 4 cartilaginous tissues of the rat craniofacial region: the nasal septal cartilage and the spheno-occipital synchondrosis (primary cartilages), and the mandibular condylar cartilage and the cartilage at the intermaxillary suture (secondary cartilages). In both primary cartilages, type II collagen was present in the extracellular matrix (ECM) of the whole cartilaginous area, but type I collagen was completely absent from the ECM. In the secondary cartilages, type I collagen was present throughout the cartilaginous cell layers, and type II collagen was restricted to the ECM of the mature and hypertrophic cell layers. These observations indicate differences in the ECM components between primary and secondary craniofacial cartilages, and that these differences may contribute to their modes of chondrogenesis.

Animals↗
PubMed1992

Prolongation of tetracaine spinal anesthesia by oral clonidine.

The effects of oral clonidine on the duration of isobaric tetracaine spinal anesthesia were studied in 30 patients undergoing urologic procedures. All patients received 15 mg of tetracaine intrathecally in isobaric saline solution. Group 1 (n = 10) received 0.25 mg of oral triazolam; group 2 (n = 10) received 0.15 mg of oral clonidine; and group 3 (n = 10) received 0.25 mg of oral triazolam and 0.75 mg of intrathecal phenylephrine. In group 1, the times for two- and four-segment regression of the level of analgesia to pin-prick were 80 +/- 17 and 123 +/- 22 min, respectively (mean +/- SD). The corresponding values of those measurements were 170 +/- 27 and 273 +/- 48 min in group 2 and 175 +/- 34 and 273 +/- 68 min in group 3. All the regression times in groups 2 and 3 were significantly longer than those in group 1. Regression times were not different between groups 2 and 3. The authors conclude that prolongation of tetracaine sensory analgesia may be produced by premedication with 0.15 mg of oral clonidine. The prolongation is similar to that produced by intrathecal phenylephrine.

Administration, Oral↗
PubMed1992

[Surgical outcome of 32 cases in traumatic subdural hygroma].

32 cases of traumatic subdural hygroma (TSH) in adults with surgical treatment were retrospectively investigated by means by clinical features and CT findings. The cases consisted of 29 males and 3 females, aged 41 to 87 years (mean 69). Preparative CT scan of all cases revealed low density area and crescent shape in frontotemporal or frontoparietal subdural space. Half of the cases had bilateral lesions. At operation of TSH, color of subdural fluid collections was more water clear or xanthochromic than bloody. As a results, 22 out of 32 cases (69%) in TSH improved with surgical treatment. Many of effective cases of surgical treatment in TSH had short interval from trauma to operation and light disturbance of consciousness before operation. However, the other intracranial damage will also affect the clinical outcome of TSH, because the majority of cases in this study was accompanied by an intracranial damage including cerebral contusion, subarachnoid hemorrhage or intracranial hemorrhage. Nevertheless, surgical management for TSH was so effective that the operation should be undergone sooner interval from trauma, simultaneously considering the another intracranial lesions except TSH. But then, we experienced 7 cases (22%) of ventricular dilatation and 5 cases (16%) of chronic subdural hematoma in postoperative follow up CT scans. In 5 cases among the former, ventriculoperitonial shunt was done, and in 3 cases among the latter, burr hole evacuation was performed. Therefore, the postoperative course of TSH should require careful observation by CT scan and so on.

Adult↗