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Biomedical subjects

M Kurihara

Publications and source records attributed to M Kurihara.

At least 127 records · Page 7Linked to original sources
PubMed1997

UFT plus cisplatin for advanced gastric cancer.

In a laboratory study using an experimental peritoneum model of gastrointestinal cancer, the UFTP [tegafur and uracil (UFT) plus cisplatin] regimen was shown to provide a survival benefit compared with the UFTM (UFT plus mitomycin) regimen that has been considered standard chemotherapy for treatment of advanced carcinoma in Japan. Results indicated that a clinical benefit of the UFTP regimen could be expected. In the pilot clinical study, the UFTP regimen exhibited excellent antitumor effects and seems to improve survival. At present, we are conducting a phase II study in which the UFTP administration schedule was modified to reduce toxicity and secure a similar level of benefit compared with results of the pilot study. Positive results are anticipated.

Adolescent↗
PubMed1997

[Phase I study of S-1. S-1 Study Group].

We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).

Administration, Oral↗
PubMed1996

Peripheral alpha-linked N-acetylglucosamine on the carbohydrate moiety of mucin derived from mammalian gastric gland mucous cells: epitope recognized by a newly characterized monoclonal antibody.

To obtain a tool to study the structural characterization and the detection of mucin derived from the gastric gland mucous cells, we developed a monoclonal antibody, designated HIK1083, against mucin purified from rat gastric mucosa. In an ELISA, HIK1083 reacted strongly with the mucin purified from a deep layer of the corpus and antrum but only slightly reacted with that obtained from the surface mucosal layer. The reaction of mucin and HIK1083 was inhibited by the oligosaccharides obtained by the alkaline borohydride reduction of antigenic mucin. Two purified oligosaccharide alditols reacting with the monoclonal antibody obtained from the antigenic mucin had one and two peripheral alpha-linked N-acetylglucosamine residues, respectively, according to the evidence from NMR spectroscopy. Moreover, among the commercially available p-nitrophenyl derivatives of monosaccharides, only p-nitrophenyl-N-acetyl-alpha-D-glucosaminide inhibited the reaction of this monoclonal antibody and the antigenic mucin in a concentration-dependent manner. These results, as well as the immunohistochemical observations, indicate that alpha-linked N-acetylglucosamine residues are specifically attached to the peripheral region of the carbohydrate moiety of the mucin synthesized in and secreted from the gastric-gland-type cells, and indicate that the monoclonal antibody HIK 1083 recognizes this structure.

Acetylglucosamine↗
PubMed1996

Incidence of intracranial meningiomas in Nagasaki atomic-bomb survivors.

Among the Nagasaki atomic-bomb survivors registered at the Scientific Data Center for Atomic-Bomb Disaster, Nagasaki University School of Medicine, 45 cases of surgically treated intracranial meningioma were collected from 6 hospitals with departments of neurosurgery in or near Nagasaki City during the period from 1973 to 1992. All 45 patients were over 40 years of age at the time of diagnosis. Subsequently, the 45 cases were statistically analyzed in relationship to the estimated distance from the hypocenter by age, gender, intracranial location, histology and latent period. The analysis showed a high correlation between incidence of meningiomas and distance from the hypocenter. The incidence among Nagasaki atomic-bomb survivors over 40 years of age, especially in those proximally exposed, appears to be increasing, in inverse proportion to the exposure distance, since 1981, 36 years after the explosion of the atomic bomb.

Adult↗
PubMed1996

Sialosyl-Tn antigen as a marker of gastric cancer progression: an international study.

Sialosyl-Tn, a mucin-associated carbohydrate antigen, is not expressed by normal mucus-producing cells of the stomach but becomes expressed in metaplastic, pre-malignant and malignant gastric tissues. Reports vary as to the frequency of STn expression and its prognostic role in gastric cancer. To determine whether these differences might be due to inter-country variations in gastric cancer biology, we immunohistochemically analyzed 340 gastric cancers from 2 countries at high-risk (high incidence) for gastric cancer (Japan and Chile), one with intermediate risk (Brazil) and one with low-risk (USA). Expression of STn was correlated with clinico-pathological features of the tumors and with cancer-related survival. Regardless of country, the frequency of STn-positive tumors was lower in non-invasive ("early") than in advanced gastric cancer. Consequently, high-risk countries where early gastric cancer is more common demonstrated a lower overall frequency of STn-positive tumors. In all 4 countries, STn expression directly correlated with depth of invasion, stage, and lymph node involvement. In addition, STn expression correlated with a poor prognosis in all 4 countries, but the effect of STn on survival was not independent of tumor stage. Our findings indicate the need to consider the inherent gastric cancer risk and prevalence of early gastric cancer in the study population when reporting frequency of STn expression in gastric cancer. Regardless of country, however, STn expression is a marker of gastric cancer progression suggesting that cancer-associated mucins play a role in the malignant behavior of this tumor.

Aged↗
PubMed1996

Establishment of monoclonal antibodies against carbohydrate moiety of gastric mucins distributed in the different sites and layers of rat gastric mucosa.

Eight monoclonal antibodies (MAbs), designated RGM21 approximately RGM42, were generated against mucin purified from the rat gastric mucosa. By applying ELISA, all of these MAbs were proved to react not only with the purified mucin, but also with the oligosaccharide mixture obtained from the antigenic mucin by alkaline borohydride treatment. Treatment of the mucin-attached ELISA well with trypsin, sodium periodate or galactose oxidase prior to the addition of the MAb was applied to characterize these MAbs. Histochemical observation indicated that all these MAbs were able to stain the formalin fixed-paraffin embedded sections of the rat gastroduodenal mucosa. Although each of these MAbs reacted with distinct mucus-producing cells localized in particular regions of the gastroduodenal mucosa, their staining specificity could generally be classified into four groups. These MAbs might be useful for estimating the physiological and pathological changes of mucins in the gastric mucosa.

Animals↗
PubMed1996

Sanfilippo syndrome type C: a clinicopathological autopsy study of a long-term survivor.

A 39-year-old Japanese woman with Sanfilippo syndrome type C is reported. Developmental delay was observed during infancy and progressive intellectual deterioration became apparent at 2 years. Her gait became unsteady and she became bed-ridden at 22 years of age. An intestinal fistula was made because of pyloric stenosis possibly caused by accumulation of mucopolysaccharide at 37 years of age. She died of acute cardiac failure at age 39 years. Pathological changes were marked in the heart and brain. Focal necrosis of myocardial fibers with replacement fibrosis and many vacuolated cells were observed between the muscle fibers and there were many vacuolated cells in the pyloric ring. There was severe neuronal loss with gliosis and massive corpora amylacea formation in the cerebral cortex, especially in layers 2 and 3. Ballooning of neurons was less prominent than neuronal loss. There were many vacuolated cells in the mesenchymal tissues; however, this finding was much less prominent than in other types of mucopolysaccharidosis. Our patient survived much longer than others with Sanfilippo syndrome type C of similar severity.

Adult↗
PubMed1996

Trends in the incidence of female breast and cervical cancers in Miyagi Prefecture, Japan, 1959-1987.

Trends in the incidence of female breast and cervical cancers were examined, using the cancer registry data in Miyagi Prefecture, Japan, during 1959-1987. The age-standardized incidence rate of breast cancer has been increasing, while that of cervical cancer has been decreasing. Age-period-cohort models were applied to clarify the trends in incidence. For breast cancer incidence, the age-period model adequately represented the data, and demonstrated that the risk of developing breast cancer has been increasing in recent time periods. The effect of cohort on breast cancer incidence was insignificant and the full model containing age, period and cohort showed irregularities in the cohort effect. For cervical cancer incidence, the effect of period was significant, while the effect of cohort was marginal. The full model containing age, period and cohort showed that cervical cancer risk has been decreasing in recent time periods and younger birth cohorts. Using published reports, we investigated the trends in the prevalence of various risk factors and compared them with the trends in the incidence at both sites. It is suggested that the effects of period and cohort might be related to the changes in the prevalence of these risk factors as well as to improvements of the diagnostic procedures.

Adult↗
PubMed1996

Glucose-mediated alteration of cellular function in human periodontal ligament cells.

Because diabetic patients are easily led to manifest severe periodontitis, we wanted to determine whether various glucose levels interfere with normal cellular function. Human periodontal ligament (PDL) cells were cultured in glucose-free medium, or in medium containing either 1100 mg/L of glucose (normal-glucose medium) or 4500 mg/L of glucose (high-glucose medium). Cells cultured in glucose-free medium changed their morphology from spindle-shaped to round, and incorporated trypan blue in a time-dependent manner. The incorporation rate was much faster in cells with shorter cell cycles than in those with longer cycles, suggesting the involvement of cell-cycle progression in cell death. However, fragmented DNA, which suggests apoptotic cell death, was not observed in these cells. We reasoned that initial cell rounding and detachment from the culture plate might be due to the conformational changes in cell-surface receptors to fibronectin, a major extracellular matrix for fibroblasts. Western blot analysis revealed that cells cultured in glucose-free medium lost their fibronectin receptor in a time-dependent manner. In addition, fibronectin receptor expression was much higher in cells cultured in high-glucose medium than in cells cultured in normal-glucose medium. Furthermore, the over-expression of the fibronectin receptor resulted in a suppressed chemotactic response of these cells to platelet-derived growth factor. On the basis of these data, it was hypothesized that a high glucose level induced over-expression of these receptors. This might be the mechanism by which a high glucose level compromises wound healing in diabetic patients and, at least in part, might be the reason diabetic patients are subject to severe periodontal destruction.

Blotting, Western↗
PubMed1996

Cell-free production of the silkworm sex pheromone bombykol.

Cell-free production of bombykol was done by incubating a pheromone gland homogenate in the presence of NADPH, ATP, and CoA. Addition of n-hexane to the reaction mixture stimulated bombykol production, resulting in production of 238 ng of bombykol from the homogenate equivalent to 2 pheromone glands after 23 h. Removal of either NADPH, ATP, or CoA resulted in no stimulation of bombykol production, suggesting that the final step of the bombykol biosynthetic pathway is done by acyl CoA synthetase and reductase, sequentially. Incubation first with ATP or high concentrations of ATP suppressed the production of bombykol. Since incubation with ATP also inhibited conversion of [1-14C]palmitoyl CoA into 1-hexadecanol, the inhibitory action of ATP seemed attributable to inactivation of the acyl CoA reductase by phosphorylation, as mediated by a protein kinase in the homogenate. Our results suggest that the activity of acyl CoA reductase in bombykol biosynthesis is regulated by phosphorylation/dephosphorylation, and that the activation occurs by dephosphorylation as mediated by phosphoprotein phosphatase.

Adenosine Triphosphate↗
PubMed1996

[Case reports of mucosal melanoma of the head and neck].

Twelve patients with mucosal melanoma in the head and neck were treated at Yokohama city University from 1975 to 1994. The sex distribution was 5 male and 7 female, and the age ranged from 40 to 79 years-old. The highest number of patients were in their sixties. In 10 cases tumors arose in the nasal cavity, in one case in the maxillary sinus and in other case in the oral cavity. The treatment modality for this tumor consisted of various combination therapies including surgery, radiotherapy, chemotherapy and immunotherapy. Combination chemotherapy consisting of dimethyltriazeno imidazole carboxamide (DTIC, Dacarbazine), amino methyl pyrimidinyl methyl chlorethyl nitrorosourea hydrochloride (ACNU) and vincristine (VCR). Cisplatin (CDDP) was recently used for cases where other chemotherapy was not effective. Surgical treatment in the initial therapy was performed in 8 patients. In three of these 8 cases, the surgical margin was positive. One of them was dead after 9 months, another dead with complication after 1 year and the other survived free of any tumor. Immunotherapy using OK-432, interleukin-2, LAK therapy and low dose CPM was effective for some patients. The 5-year survival rate was 44%. Patients with surgical treatments in the initial therapy had longer survival than those without surgical treatments.

Adult↗
PubMed1996

[The guideline for clinical trials proposed by Japan Society for Cancer Therapy (JSCT)].

The purpose of the guideline is to improve the quality of clinical trials (especially in phase III) which are performed by the members of Japan Society for Cancer Therapy. It was summarized the following 5 points: 1) clinical studies using new anti cancer drugs after its permission by Ministry of Health of Welfare, 2) not only evaluation of the effect of new drugs, but also evaluation of multidisciply therapy of specific organ cancer, 3) the dose and administration method of the drug, which was admitted by ministry of Health & Welfare may be deviated by researcher, 4) true endpoint the therapy is patients' survival and 5) verification of hypothesis is requested to perform well planned randomized controlled trials. Much more, the problems of its clinical application, eg. qualification and authorization of coordinator, evaluation criteria (each organ specific evaluation criteria made by JSCT must be used in the clinical studies), evaluation of QOL, were referred.

Antineoplastic Agents↗
PubMed1996

[Prognosis of severe head injury in childhood: from the viewpoint of brain plasticity].

We investigated prognosis of 12 children with severe head injury, whose Glasgow Coma Scale (GCS) was less than 8 during the acute period. We divided the cases into two groups according to the age of incidence: less than 4 years (6 cases) and more than 4 years (6 cases). We examined the acute conditions (cause, type of the lesion, GCS, period of consciousness loss) and the present status (disability, intelligence quotient: IQ, functional independence measure: FIM). We used IQ and FIM scores for the indices to assess prognosis, and compared those two groups. IQ and FIM scores were better in the group whose onset was under 4 years. This difference was thought to be related to the greater plasticity and to the rehabilitation effect in younger brain.

Adolescent↗
PubMed1996

[Meigs syndrome presenting as diaphragmatic pleural nodules].

A 52-year-old woman was admitted to our hospital because of non-productive coughing and dyspnea on exertion. A chest X-ray film revealed a moderate pleural effusion. The effusion was persistent and progressive in spite of repeated thoracentesis. Because examinations of the effusion did not result in a specific diagnosis, thoracoscopy was done under local anesthesia. Two nodules were found in the surface of the diaphragmatic pleura. Examination of biopsy specimens revealed mesothelial hyperplasia and lymphatic duct proliferation without malignant or granulomatous lesions. Systemic examinations revealed a tumor in the right ovary. The tumor was removed, and examination revealed that it was a serous adenofibroma without malignant lesions. Meigs syndrome was diagnosed. The pleural effusion disappeared quickly, two weeks after the operation. We know of no previous report of diaphragmatic pleural nodules in a case of Meigs' syndrome. Meigs' syndrome should be considered in the differential diagnosis of pleural nodules.

Adenofibroma↗
PubMed1996

[Phase I study on DMDC].

Phase I study on antimetabolic carcinostatic DMDC was conducted at 16 medical institutions nationwide for patients with various types of malignant tumors. DMDC was administered by intravenous infusion as per the following three schedules: single administration, single repeated administration, and 5-consecutive-day administration. The safety of the compound was examined single administration in 16 patients, by the single repeated administration in 5 patients, and by the 5 consecutive-day administration in 7 patients, for a total of 28 patients. In the single administration trial, 200 mg/m2 (1 n) was given as an initial dose, then increased stepwise to 450 mg/m2 (2.25 n). The single repeated administration trial was conducted at a single dose of 300 mg/m2. One treatment course lasts until recovery from side effects and abnormalities in laboratory test values. As a general rule, the administration was repeated for 2 treatment courses or more. In the 5-consecutive-day administration trial, an initial dose was 30 mg/m2/day (1 n), and increased to 40 mg/m2/day (1.3 n). The dose-limiting factors for both the single and 5-consecutive-day administration trials were decreases in the numbers of leukocytes and neutrophils. The maximum tolerated dose for single administration trial was over 400 mg/m2 (2 n), and for the 5-consecutive-day administration trial 40 mg/m2 (1.3 n). The decrease in the number of leukocytes and neutrophils for both the single administration and 5-consecutive-day administration trial reached its nadir one to two weeks after administration, and recovered in about one week. In the single repeated administration trial, the administration interval for patients who had completed 2 courses was 2 approximately 3 weeks. The plasma half-life of DMDC in the final phase of elimination in the single administration trial was 5.2 approximately 6.3 hours, and no differences were seen among dose levels. The urinary excretion rate was between 32.0 approximately 61.5% until 48 hours after administration. No accumulation was seen in the 5-consecutive-day administration trial. There were no findings to suggest an antitumor effect in the present study. Given the recovery pattern for suppression of marrow, the above mentioned results led us to decide that an recommended method of administration and dosage in an early phase II trial would be 300 mg/m2 per administration by an intravenous infusion every 2 approximately 3 weeks.

Aged↗