Biomedical subjects

M Kurihara

Publications and source records attributed to M Kurihara.

At least 91 records · Page 5Linked to original sources

PubMed1999

Rat gastric mucins recognized by monoclonal antibodies RGM21 and HIK1083: isolation of mucin species characteristic of the surface and glandular mucosa.

Whole mucins and reduced subunits were extracted from the corpus of the rat stomach. After purification by Sepharose CL-4B chromatography followed by cesium trifluoroacetate equilibrium centrifugation, they were analyzed by Sepharose CL-2B chromatography, rate-zonal sedimentation centrifugation, and Q-Sepharose chromatography. Monoclonal antibodies RGM21 and HIK1083, which histochemically stained mucins in the surface and glandular mucosa of the rat stomach, respectively, were used to detect the site-specific mucins. Although RGM21- and HIK1083-reactive mucins both had a multimerized structure, the density and size of both the whole mucins and reduced subunits differed, thus indicating the presence of distinct mucin species in the surface and glandular mucosa. The mucin subunits were separated into four fractions, UB, B1, B2a, and B2b, by Q-Sepharose chromatography. HIK1083 reacted mainly with UB, while RGM21 reacted with B1, B2a, and B2b. These results, combined with dot-blot, amino acid, and carbohydrate composition analyses, showed that the surface mucins may consist of three kinds of subunits. In contrast, the glandular mucins may consist of one kind of subunit which differs from that of surface mucins.

Amino Acids↗

PubMed1999

Phase II study of raltitrexed (Tomudex) in chemotherapy-pretreated patients with advanced colorectal cancer. Tomudex Cooperative Study Group.

Raltitrexed (Tomudex), a novel folate-based inhibitor of thymidylate synthase, has demonstrated anti-tumour efficacy comparable with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer (CRC). This phase II study was conducted to evaluate the anti-timor efficacy and tolerability of raltitrexed in patients with advanced CRC who had received one previous chemotherapy regimen. Raltitrexed was administered at a dose of 3.0 mg/m2 i.v. over 15 min once every 3 weeks. Of 43 eligible patients, 53% had colon cancer and 47% rectal cancer. Objective responses were observed in 16% of patients [95% confidence interval (CI): 7-31%; seven partial responses). The median duration of response was 101 days (range: 45-239 days), the median overall duration of response was 145 days (range: 104-302 days) and the median survival was 11.6 months (95% CI: 9.4-14.7 months). Liver metastases showed a 17% (three of 18) response rate and lung metastases a 12% (three of 25) response rate. Adverse events of grade 3 or 4 reported for more than 5% of patients were neutropenia (23%), leukopenia (9%), reversible SGPT increase (7%) nausea/vomiting (19%), anorexia (14%), asthenia (9%) and hypotension (7%). Grade 3 or 4 diarrhea, stomatitis and alopecia were not observed. In summary, raltitrexed had an acceptable toxicity profile and promising anti-tumor activity against advanced CRC in patients who had received prior chemotherapy. Further clinical trials of combination chemotherapy using raltitrexed are warranted.

Adult↗

PubMed1999

Prediction of response to 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with inoperable advanced gastric cancer by immunostaining of thymidine phosphorylase/platelet-derived endothelial cell growth factor.

BACKGROUND: No reliable method is available for predicting the response to chemotherapy in patients with gastric cancer. The anticancer drug 5'-deoxy-5-fluorouridine (5'-DFUR) is converted into 5-fluorouracil (5-FU) by thymidine phosphorylase (dThdPase). We studied the relation between the expression of dThdPase in tumor tissue and the response to treatment with 5'-DFUR to determine if this enzyme can be used to predict the response to chemotherapy. METHODS AND MATERIALS: We performed endoscopic biopsy and studied the expression of dThdPase by immunostaining with anti-dThdPase monoclonal antibody in 41 patients with inoperable advanced gastric carcinomas before they received multiple-drug chemotherapy, including 5'-DFUR. The relation between the expression of dThdPase and the response to chemotherapy was studied. We also studied the characteristics of positive cells against anti-dThdPase monoclonal antibody. RESULTS: The response rate among patients whose tumors were positive for dThdPase expression (56.8%, 21/37) was higher than that among patients whose tumors were negative for dThdPase expression (0%, 0/4; p = 0.048). Spindle-shaped cells darkly expressing dThdPase were sporadically seen surrounding cancer nests in some patients. Multiple-antibody immunostaining suggested that these spindle-shaped cells were perivascular mesenchymal cells. The response rate was 82.4% (14/17) among patients with spindle-shaped cells strongly positive for dThdPase, as compared with 29.2% (7/24) among those with spindle-shaped cells weakly positive or negative for dThdPase (p = 0.00131). The expression of spindle-shaped cells darkly stained with dThdPase was the factor most strongly related to the response to chemotherapy (odds ratio = 35.513, p = 0.0027). CONCLUSIONS: The expression of dThdPase in stromal spindle-shaped cells may be a useful index in predicting the response to 5'-DFUR in patients with gastric cancer.

Adult↗

PubMed1999

[Investigation of school life of children with acquired brain damage].

We investigated the status of the school life of 72 children with acquired brain damage attending to different schools: special schools (30 cases), special classes in an ordinary school (9 cases), and ordinary schools (33 cases). In the special school group, the main disorder was the sequelae of encephalitis/encephalopathy; there were 26 cases unable to walk, 29 with severe mental retardation, and 25 with epilepsy. In the ordinary school group, main problems were the sequelae of a cerebrovascular disorder or a traumatic brain injury. Impairment was mild in this group; only 2 cases were unable to walk, and only 4 were mentally retarded. However, many patients had learning difficulty and costed the families much work to achieve school lives. In all groups, the use of welfare equipments improved the activity of daily living. We emphasize that welfare equipments and community support systems should be utilized for these children.

Activities of Daily Living↗

PubMed1999

[Clinical evaluation of S-1, a new anticancer agent, in patients with advanced gastrointestinal cancer. S-1 Cooperative Gastrointestinal Study Group].

In developing a new anticancer agent, it is most important to balance the antitumor activity and toxicity of the agent. S-1 was designed to achieve high activity and low toxicity. In it tegafur, a prodrug of 5-FU, is combined with two classes of modulators. CDHP, an inhibitor of 5-FU degradation in the liver, and Oxo, an inhibitor of 5-FU phosphoribosylation in the digestive tract. In both early and late Phase II studies, S-1 was effective against advanced or recurrent gastrointestinal cancer. Toxicities were generally mild, and there were no toxic deaths.

Administration, Oral↗

PubMed1999

[A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer: a cooperative study group trial (group B)].

A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer was performed to evaluate the anti-tumor activity and clinical toxicity as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of 72 patients enrolled, 63 patients were eligible and 59 patients were evaluable for response. The anti-tumor effects obtained complete response (CR) in one patient partial response (PR) in 13, minor response (MR) in 3, no change (NC) in 20, and progressing disease (PD) in 22 patients. The overall response rate in 59 patients was 23.7% (14/59). For 14 CR or PR cases, a response appeared 10 to 107 days (median 33.5 days) and 1 to 8 (median 2) times of dosing after the initial administration. The response rate was 9.5% in the primary tumor, 31.3% livers, 50.0% abdominal tumor, and 24.1% lymph nodes, respectively. The major adverse reactions were gastrointestinal symptoms including nausea/vomiting, anorexia, fatigue, alopecia and fever. Leukocytopenia and neutrocytopenia were also observed with a high incidence, but they recovered after 8 days from the nadir. The results show that docetaxel is an effective anti-tumor agent for advanced or recurrent gastric cancer. It is necessary to conduct another clinical trial by concomitant administration with other anti-tumor agents.

Adenocarcinoma↗

PubMed1999

[Results of questionnaire to 56 medical institutions about clinical trials of cancer chemotherapy].

From the stand point of investigators doing clinical trials of anti-cancer drugs, a questionnaire to survey of the current status of clinical trials concerning on the reactions of medical institutions to the new GCP started in April 1997, sent to 75 institutions all over the Japan. 56 institutions (75%) gave answers to the questionnaire, in August 1998. As the results, apparent decrease of Phase II & III trials were noticed compared the numbers before March 1997. IRB with one or two outside members are well functioned in these institutions. But, training related doctors, nurses (especially CRC) are nowadays most important problems, which are strongly expected to Ministry of Health and Welfare and related medical societies, for instance Japan Society of Clinical Oncology.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

[Advances in endoscopic therapies for cancers of the digestive tract].

Endoscopic therapies for the treatment of cancers of the digestive tract have been improved. Today, some early cancers can be curatively treated by endoscopy (endoscopic polypectomy, endoscopic mucosal resection, heatprobe method, etc.). In addition, endoscopic local injection chemotherapy is performed for some advanced cancers as an adjuvant therapy. Recent progress in endoscopic therapies for cancer is reviewed in this paper, including their historical background. Improvements in these endoscopic treatment methods are expected to provide increased advantages for the treatment of patients with cancer in the near future.

Colonic Polyps↗

PubMed1999

Methane production and energy partition of cattle in the tropics.

The aim of this experiment was to determine CH4 production and energy partition for a range of diets fed to Bos indicus cattle. Six Brahman cattle were fed on three different diets in a replicated Latin square experiment over three periods. The diets were (1) long-chopped Angleton grass (Dicanthium aristatum) hay ad libitum (DM digestibility (DMD) 41 (SE 2)%; 4 g N/kg), (2) long-chopped Rhodes grass (Chloris gayana) hay ad libitum (DMD 60 (SE 1)%; 14 g N/kg) or (3) 2 kg long-chopped lucerne (Medicago sativa) hay/d plus a high-grain diet (ad libitum) (DMD 70 (SE 1)%; 31 g N/kg). CH4 production was measured using confinement-type respiration chambers. Metabolizable energy intake (MJ/d) of cattle fed on Angleton grass (18.4 (SE 2.0)) was lower (P < 0.01) than that for Rhodes grass (54.9 (SE 2.1)), which was lower (P <0.01) than that for the high-grain diet (76.7 (SE 5.8)). CH4 production (g/d) for cattle fed on Rhodes grass (257 (SE 14)) was higher (P < 0.01) than that for cattle fed on both the high-grain diet (160 (SE 24)) and Angleton grass (113 (SE 16)). CH4 conversion rate (MJ CH4 produced per 100 MJ gross energy intake) was not significantly different between cattle fed on Angleton (10.4 (SE 1.1)) and Rhodes (11.4 (SE 0.3)) grass, but was higher (P < 0.01) than for cattle fed on the high-grain diet (6.7 (SE 0.7)). CH4 production (g/kg live-weight gain) was associated (P < 0.001) with both live-weight gain and feed:gain ratio. We conclude that the relationships between CH4 production, energy utilization and live-weight change of cattle fed on tropical forages differ from those of cattle fed on diets based on temperate forages.

Analysis of Variance↗

PubMed1999

[Functional outcome after diffuse axonal injury in childhood traumatic brain injury].

We investigated the functional prognosis after traumatic diffuse axonal injury in children. We evaluated the status of the acute stage, as well as the functional independence measure (FIM) and intelligence quotient (IQ) at 4, 12, and 24 months after the injury. Physical disabilities persisted in all but 1 case, but 5 cases could walk by themselves after 1 year. IQ at 2 years after the injury was 64 in one case, but between 81 and 100 in others. Concerning the higher cortical function, all cases showed memory disturbance. None developed epilepsy. All cases showed abnormalities on cerebral MRI. Five of the 7 cases showed EEG abnormalities. As to the course of recovery scaled by FIM and IQ, marked improvement was seen in 4 cases during the first 4 months, 3 cases during the first 1 year. After 1 year, the degree of improvement became slower in all. All cases showed learning disability at school.

Activities of Daily Living↗

PubMed1999

Low-dose cisplatin and 5-fluorouracil in combination can repress increased gene expression of cellular resistance determinants to themselves.

The synergistic mechanism of cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear, despite its substantial antitumor activity, which has been demonstrated clinically. To clarify the mechanism(s), we determined the sensitivity or resistance factors to either drug in seven gastrointestinal cancer cell lines and then analyzed the altered gene expression after different exposures to CDDP and 5-FU. At the basal gene expression level, glutathione S-transferase pi (GSTpi) expression correlated with the observed resistance to CDDP, whereas dihydropyrimidine dehydrogenase (DPD) and multidrug resistance-associated protein (MRP) expression was related to 5-FU resistance. GSTpi, DPD, and MRP expression increased in response to the respective drug, but they also increased in response to the other drug as well. Additionally, 5-FU revealed a drastically increased thymidylate synthase (TS) gene expression in 5-FU-resistant cells. However, the increasing actions of CDDP and 5-FU on GSTpi, DPD, MRP, and TS expression varied according to the exposure time, concentration, and schedule. A low concentration of CDDP (1 microg/ml, 30 min) followed by 5-FU (0.5 microg/ml, 72 h) was found to cause a less increased expression of DPD, MRP, GSTpi, and TS than either drug alone, thus resulting in synergistic cytotoxicity in 5-FU-resistant COLO201 and CDDP-resistant HCC-48 cells. The sequential combination of CDDP and 5-FU inhibited the growth of human normal renal proximal tubule cells by less than 20%. Low concentrations of CDDP followed by continuous exposure to 5-FU can repress increased gene expression related to both drug resistances, thereby being synergistically cytotoxic in human gastrointestinal cancer cells.

ATP-Binding Cassette Transporters↗

PubMed1999

[Two regimens of combined 5'-deoxy-5-fluorouridine and cisplatin showing different dose intensities--investigation based on relative performances].

Patients with inoperable gastric cancer were given either of two regimens of combined 5'-deoxy-5-fluorouridine and cisplatin with different dose intensities. The results were compared based on ratios of the actual and the scheduled total doses of the regimens [relative performance (RP)]. The overall response rates and survival curves between the regimens showed no differences, but the incidences of severe adverse drug reactions was higher with regimen A, which had a higher dose intensity. Furthermore, survivals with regimen A were no different between the responding and non-responding patients, whereas the survivals of responding patients under regimen B were significantly longer than those of non-responding patients. Average RP were 0.87 with regimen A and 0.93 with regimen B. The mean RP of responding and non-responding patients were 0.94 and 0.84, respectively, with regimen A, and 0.99 and 0.89 with regimen B. Regarding survivals in both the RP = 1.0 and the RP < 1.0 groups, no difference was observed with regimen A. However, with regimen B, the RP = 1.0 group exhibited significantly better survival curves. Furthermore, survivals of the RP = 1.0 group under regimen B were much more favorable than in the RP = 1.0 group under regimen A. The above findings show that a regimen with an appropriate dose intensity has a favorable survival effect on patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

[Consideration of cancer home chemotherapy with cooperation between hospital and clinic].

Recently, the progress in chemotherapy has brought an improvement in the survival rate of patients with non-resectable digestive tract cancer. Simultaneously, maintenance of patients' QOL is regarded as important. In our hospital, we use low-dose FP therapy to maintain QOL and a satisfactory survival rate. To date, we have administered low-dose FP to more than 50 patients with non-resectable digestive cancer. We investigated patients who received home chemotherapy after being evaluated NC, and found no remarkable side effects as a result of this therapy during admission.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

[Computational study on antioxidation mechanism of catechins].

All C-H and O-H bond dissociation enthalpies (BDE's) in catechins, (-)-epigallocatechin) were calculated by semi-empirical molecular orbital calculation using the SPARTAN program. The BDE's of benzyl hydrogens (C-2 position in catechins) were found to be quite low. This suggests that abstraction of benzyl hydrogen is crucial step for antioxidative activity. This is corroborated by the reported results of LC/MS and spectrophotometric analysis of reaction intermediates from catechins treated with AAPH.

Antioxidants↗

PubMed1999

[Molecular mechanics study on Conformation of a homooligopeptide constituted by isovalin].

Conformational energy computations on a homo-hexapeptide of (S)-isovaline were performed using molecular mechanics on MacroModel. Conformational search calculations were carried out by Monte Carlo method. AMBER* was used as the force field. The global minimum energy conformation was found to be a 3(10)-helix coordinated by four hydrogen bonds. The results of the theoretical analysis of the conformation of the peptide are in agreement with its reported conformational properties in the solid state determined by X-ray crystallographic analysis.

Crystallography, X-Ray↗

PubMed1998

A new congenital muscular dystrophy with mitochondrial structural abnormalities.

We report a new form of congenital muscular dystrophy (CMD) in 4 patients from three unrelated families with probable autosomal-recessive inheritance. All patients had the clinical characteristics of merosin-positive congenital muscular dystrophy, but had marked mental retardation. The disease was slowly progressive and 1 patient died from dilated cardiomyopathy at the age of 13 years. In addition to dystrophic changes with necrosis and regeneration in muscle, the most striking finding was mitochondrial depletion in the center of the sarcoplasm. Mitochondria at the periphery of fibers were markedly enlarged ("megaconial" appearance) with complicated cristae, and contained a normal amount of mitochondrial DNA by in situ hybridization. Mitochondrial enlargement may represent functional compensation for mitochondrial depletion in the central sarcoplasm, where myofibrillar degeneration occurred.

Adolescent↗

PubMed1998

A ribosomal protein gene cluster is encoded in the mitochondrial DNA of Dictyostelium discoideum: UGA termination codons and similarity of gene order to Acanthamoeba castellanii.

We sequenced a region of about 14.5 kb downstream from the ribosomal protein L11 gene (rpl11) in the mitochondrial DNA (54+/-2 kb) of the cellular slime mold Dictyostelium discoideum. Sequence analysis revealed that eleven ribosomal protein genes and six open reading frames (ORFs) formed a cluster arranged in the order: rpl11-orf189-rps12-rps7-rpl2-rps19-+ ++orf425-orf1740-rpl16-rpl14-orf188- rps14-rps8-rpl6-rps13-orf127-orf796. This order was very similar to that of homologous genes in Acanthamoeba castellanii mitochondrial DNA. The N-terminal region of ORF425 and the C-terminal region of ORF1740 had partial similarities to the S3 ribosomal protein of other organisms. The termination codons of rpl16 and orf188 were UGA, which has not hitherto been found in genes encoded in D. discoideum mitochondrial DNA.

Acanthamoeba↗

PubMed1998

New monoclonal antibodies against gastric gland mucous cell-type mucins: a comparative immunohistochemical study.

The immunohistochemical reactivity of monoclonal antibodies raised against rat and pig gastric mucins (HIK1083, PGM36, and PGM37) was investigated in normal gastrointestinal tracts obtained from fish, amphibians, reptiles, birds, and mammals (including humans). These monoclonal antibodies exhibited highly selective reactivity with class III mucins, as identified by paradoxical concanavalin A stain, in the gastrointestinal tract of vertebrates. All three monoclonal antibodies reacted with the mucous neck cells and pyloric gland cells of amphibians, reptiles and mammals, the cardiac glands of reptiles and mammals, and Brunner's glands of mammls. The deep crypt secretory cells of the rat colon and certain goblet-type cells deep in crypts in the pig colon differed from the above pattern only in that they did not show immunoreactivity with monoclonal antibody PGM36. These data suggest that the development of class III mucin is a fundamental evolutionary characteristic of vertebrate gastric mucins. These monoclonal antibodies should prove useful for the investigation of cell differentiation among gastrointestinal mucous cells and for the biochemical analysis of gastrointestinal mucins in different species.

Animals↗