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Biomedical subjects

M Kurihara

Publications and source records attributed to M Kurihara.

At least 109 records · Page 6Linked to original sources
PubMed1998

Comparison of four monoclonal antibodies reacting with gastric gland mucous cell-derived mucins of rat and frog.

Features of four monoclonal antibodies (MAbs), PGM36, PGM37, PGM38 and HIK1083, reacting with the mucin derived from rat gastric gland mucous cells were compared. By applying enzyme linked immunosorbent assay, all of these MAbs reacted not only with the mucins purified from both rat and frog stomach, but also with the oligosaccharides obtained from the antigenic mucins by alkaline borohydride treatment. These MAbs could be characterized as distinct MAbs due to the immunohistochemical observation of rat cecal mucosa and the reactivity to paranitrophenyl derivatives of monosaccharides. These MAbs might be useful tools to compare the gastric gland-type mucins in different species of vertebrates and to investigate the heterogeneity of the carbohydrate structure of the mucin molecules of various origins.

Animals↗
PubMed1998

Prognosis in severe motor and intellectual disabilities syndrome complicated by epilepsy.

We investigated the prognosis of epilepsy in 54 patients with severe motor and intellectual disabilities syndrome (SMIDS). The prevalence of epilepsy was 75.7% in our institution for SMIDS. We assessed activities of daily living (ADL) of them at the onset of epilepsy and at present, according to the scores in locomotion, language, toileting, dressing and feeding. Among them, patients with uncontrolled epilepsy constituted 40.3%. ADL scores worsened in the uncontrolled group, while they improved in other cases. Early seizure control is very important in SMIDS for improving patients' quality of life.

Activities of Daily Living↗
PubMed1998

Advance directives and other medical decisions concerning the end of life in cancer patients in Japan.

The purpose of our survey was to investigate the experience of physicians regarding advance directives and other medical decisions concerning the end of life. A postal questionnaire was sent to 500 Japanese physicians who were most involved in medical care of terminal patients. A total of 339 (68%) physicians responded. In dealing with terminal patients, approximately half gave priority to their patients' wishes for medical care, if known, regardless of the patient's competency. Of the respondents, 149 had been presented with advance directives by their patients and 35% followed all advance directives presented in their practice. Cardiopulmonary resuscitation (CPR) for arrested patients to enable their family to be at the bedside at the time of the death was common. More than 60% of the respondents thought that active euthanasia and assisted suicide were never ethically justified. Our study indicates that the wishes of patients are currently not always given top priority in medical decisions concerning the end of life.

Adult↗
PubMed1998

Elevation of cytoplasmic cytochrome c in radiation-induced apoptosis.

The signal transduction pathway involved in radiation-induced apoptosis remains unclear, especially as regards the site at which the primary effect of radiation occurs. In this study, we demonstrate that cytochrome c may be released from mitochondria into the cytosol after irradiation, but that direct irradiation of isolated mitochondria induces no elevation of cytochrome c release. These observations suggest that cytochrome c and mitochondria may be involved in the radiation-induced apoptotic pathway, but mitochondria might not be a target of radiation, and that a signal transduction pathway from an unknown target might exist upstream of mitochondria during radiation-induced apoptosis.

Apoptosis↗
PubMed1998

Distinct effects of tetragastrin, histamine, and CCh on rat gastric mucin synthesis and contribution of NO.

Although gastrin, histamine, and carbachol (CCh) accelerate gastric mucin metabolism, information about their target cells of mucin production is lacking. To clarify this, we examined the effects of these stimulants, including the possible participation of nitric oxide (NO), on mucin biosynthesis in distinct sites and layers of rat gastric mucosa. Pieces of tissue obtained from the corpus and antrum were incubated in a medium containing radioactive precursors and each stimulant, with or without NO synthase (NOS) inhibitor. Distribution of NOS was compared with that of the specific mucins by immunostaining using specific antiserum and monoclonal antibodies. In the full-thickness corpus mucosa, tetragastrin enhanced [3H]glucosamine incorporation into mucin but had no effect on [14C]threonine incorporation. Both histamine and CCh dose dependently increased 3H- and 14C-labeled corpus mucin. Only CCh stimulated antral mucin biosynthesis. CCh stimulation was noted in the corpus mucosa after removal of surface mucous cells, but stimulation by tetragastrin or histamine disappeared as a result of this pretreatment. Only tetragastrin-induced activation was completely blocked by the NOS inhibitor. NOS immunoreactivity was limited to surface mucous cells. Mucus-producing cells present in the different sites and layers of the gastric mucosa have distinct mechanisms for regulation of mucin biosynthesis. Gastrin-stimulated mucin biosynthesis mediated by NO is limited to surface mucous cells of rat gastric oxyntic mucosa.

Animals↗
PubMed1998

Histochemical reactivity of normal, metaplastic, and neoplastic tissues to alpha-linked N-acetylglucosamine residue-specific monoclonal antibody HIK1083.

Monoclonal antibody (MAb) HIK1083, which is obtained by immunizing mice with a preparation of rat gastric mucins, has been shown to bind specifically to alpha-linked N-acetylglucosamine (alpha-GlcNAc). We investigated the specificity of MAb HIK1083 by immunostaining normal human organs, mucinous metaplasia of human pancreas, adenocarcinomas of human stomach, pancreas, and colon, and normal rat organs. The specificity was investigated by making comparisons with (a) a stain that labels Class III concanavalin A (ConA)-reactive mucin (Class III mucin), i.e., paradoxical ConA (PCS), and (b) staining with horseradish peroxidase (HRP)-conjugated Griffonia simplicifolia agglutinin II (GSA-II). In normal human and rat organs and in mucinous metaplasia of human pancreas, immunostaining with MAb HIK1083 and PCS showed similar specificities for mucins in glandular mucous cells. In adenocarcinoma of stomach and pancreas, GSA-II showed the most widespread positivity, PCS showed the least, and MAb HIK1083 showed a reactivity between those two extremes. Colon adenocarcinomas were labeled only with GSA-II. These results demonstrate that MAb HIK1083 could be a useful screening tool for Class III mucin in normal, metaplastic, and carcinoma tissues, and that the alpha-GlcNAc residue is one of the specific sugar residues found in Class III mucin.

Acetylglucosamine↗
PubMed1998

Hardness controlled enzymes and electronegativity controlled enzymes: role of an absolute hardness-electronegativity (eta-chi) activity diagram as a coordinate for biological activities.

We found that absolute hardness-absolute electronegativity (eta-chi) activity diagrams play an important role as a new coordinate of bioactivity in structure-activity relationships. In this paper, the eta-chi activity diagram, focusing on the molecular mechanism of bioactive compounds is used to discuss two major problems. First, the potency of bioactivities for xenobiotics such as polychlorinated dibenzo-p-dioxins (PCDDs) 3 and polychlorinated biphenyls (PCBs) 4, were found to be strongly related to their absolute hardness (eta). Second, the antibacterial activity of new quinolones such as norfloxacin 1 and enoxacin 2, was found to be strongly related to their absolute electronegativity (chi). These findings predict at least two chemical properties for a hardness-controlled or electronegativity-controlled enzyme.

4-Quinolones↗
PubMed1998

Periodontal disease as a complication of diabetes mellitus.

Based on our clinical observations that patients with insulin-dependent diabetes mellitus (IDDM) are subject to periodontal disease, we developed the hypothesis that hyper- or hypoglycemia might contribute to the pathogenesis of diabetic periodontitis. In this article, experimental facts that substantiate this hypothesis are presented on the basis of our studies and then discussed. Hyperglycemia progressively glycates body proteins, forming advanced glycation end products (AGE), which stimulate phagocytes to release inflammatory cytokines such as TNF-alpha and IL-6. In this context, to understand the effects of hyperglycemic episodes on periodontal health, 24 adolescent IDDM patients were examined for their periodontal status, and 3 of them were found to have periodontitis. Laboratory analyses on these 3 patients revealed that 2 had elevated serum TNF-alpha levels. These results may partly support the current hypothesis of a mechanism of diabetic complications in which abnormal cytokine levels induced by AGE could exacerbate inflammatory responses. In IDDM patients, the diabetes is often accompanied not only by hyperglycemic episodes but also by iatrogenic hypoglycemia. Periodontal ligament cells (PDL) cultured under hyperglycemic conditions were impaired in such biological functions as adhesion and motility, while cells cultured under hypoglycemic conditions (10 mg/dL) gradually dissociated from their anchor and underwent cell death. These phenomena correlated well with the expression profile of fibronectin receptor. Interestingly, these changes due to the different glucose levels were observed more intensively in PDL than in other fibroblastic cells, suggesting that the biological functions of PDL are easily led to impairment by variation or rapid fluctuation of glucose levels. These observations suggest that hyperglycemia could indirectly exacerbate inflammatory tissue destruction through the body's scavenger system against AGE, and that both hyper- and hypoglycemia might directly impair the biological functions of periodontal connective tissues through cell-matrix interactions.

Adolescent↗
PubMed1998

[Stereoselective epoxidation with bulky dioxiranes generated from substituted cyclohexanones].

Dioxiranes have recently been shown to be important and versatile oxidants, which are generated from potassium monoperoxysulfate (KHSO5) and ketones. Dimethyldioxirane, a dioxirane generated from acetone as a ketone, is particularly useful as an oxidation reagent with a broad scope of synthetic applications. Several papers have been reported about stereoselective epoxidation using dimethyldioxirane. However, there have been only a few examples using dioxiranes generated from other ketones. Dioxiranes derived from sterically hindered ketones are expected to be "bulky oxidant", and to be useful for stereoselective epoxidation. In a CH2Cl2-buffered water (two-phase system) in the presence of phase-transfer agent under neutral condition (pH 7.8) according to the reported procedure, the epoxidations with hindered alpha-substituted cyclohexanones proceeded in very low yields. After a survey of possible conditions we found that basic (pH 11) CH2Cl2-MeOH-buffer system was effective for the epoxidations of olefins with Oxone (active constituent KHSO5) and substituted cyclohexanones. We carried out epoxidation of cyclohexen derivatives with dioxiranes derived from alpha-substituted cyclohexanones in a CH2Cl2-MeOH-buffer solvent system at pH 11. High trans selectivities were obtained. Furthermore, according to this method acyclic silyl ethers were stereoselectively oxidized to afford erythro epoxides.

Chemistry, Organic↗
PubMed1998

[Phase I study of orally administered UFT plus l-leucovorin].

A Phase I study of UFT plus l-LV was conducted in 29 patients (pts) with G.I. cancer on a multicenter cooperative study. UFT and l-LV were given orally in two divided doses for 28 consecutive days, followed by a 14 day-rest period. UFT was fixed in three doses, 250, 313 and 375 mg/m2/day, and l-LV was increased in dose from 25 to 50 and to 100 mg/body/days. Dose-limiting toxicities were anorexia, diarrhea, and nausea/vomiting. The maximum tolerated dose of UFT was 375 mg/m2/day, and l-LV 25 mg/body/day. Severe myelotoxicity was not observed. There were three responders (PR) out of 21 pts with measurable disease at UFT doses of 313 mg/m2/day and l-LV 50 and 100 mg/body/day. Responses observed were abdominal mass (rectal ca), liver metastasis (pancreas ca) and metastasis of liver and lymph-node (gastric ca). As a result of pharmacokinetics, plasma concentrations of 5-methyl-THF were maintained > 1.0 microM for over 5 hours that was considered to have a modulating effect on the plasma concentration. In doses of 50 mg and 100 mg/body/day of l-LV. No accumulations in plasma were observed in patient treated in 28 days by l-LV/UFT therapy. It was suggested UFT and l-LV did not interfere with each other's absorption. A Phase II study is recommended, with doses of 313 mg/m2/day of UFT and 50 or 100 mg/body/day of l-LV.

Administration, Oral↗
PubMed1998

[Cancer chemotherapy in patients of advanced age (over 75)].

Generally, elderly patients are excluded from therapeutic trials because of decreased tolerance to chemotherapy. We discussed chemotherapy cancer patients of an advanced age based on our experience of malignant lymphoma and advanced gastric cancer patients over 75 years of age. We found the tendencies for diagnosis at more advanced stages involved many complications, especially 10% of cases have double cancer, and not good performance status in these patients. Some 53 cases of malignant lymphoma were treated with combination chemotherapy including anthracycline, obtained prolongation of survival in responder. On the other hand, 64 cases of advanced gastric cancer were treated with palliative chemotherapy. Some clinical trials have showed that older and younger patients were no different in terms of response, toxicity and overall survival. But these selected elderly patients could be entered in clinical trials, seemed to have to have surprisingly good health, no historical complications and good performance status, in spite of suffering from cancer. Not only chronological age but also the kinds of cancer and performance status are important justification for decisions to limit or withhold treatment.

Aged↗
PubMed1998

DNA fragmentation induced by a cytoplasmic extract from irradiated cells.

Apoptosis is a mode of cell death characterized by distinct morphological features and DNA fragmentation. The program that leads to apoptosis has been considered to be predominantly extranuclear, and a signal transduction pathway to the nucleus exists during apoptosis, while characteristic events occur in the nucleus. As for radiation-induced apoptosis, the signal transduction pathway remains unclear, especially the sites where the primary effect of radiation occurs. In this study, we demonstrate that a cytoplasmic extract prepared from irradiated cells has the ability to cause DNA fragmentation and that caspase-3 is activated in this extract. Normal nuclei of HeLa S3 cells were added to a cytoplasmic extract made from HL60 cells which had been irradiated with 30 Gy of 137Cs gamma rays and were incubated. Agarose gel electrophoresis of the added nuclei showed a characteristic DNA laddering pattern. This reaction was blocked by a caspase-3 inhibitor but not by an ICE inhibitor. These observations suggest that a signal transduction pathway from an unknown target of gamma radiation may exist upstream of caspase-3 during radiation-induced apoptosis.

Caspase 3↗
PubMed1998

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer: a Japanese Cooperative Study Group trial (group A)].

A late phase II clinical study of RP56976 (docetaxel) was conducted in patients with advanced/recurrent gastric cancer as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of the 76 patients enrolled, 66 patients were eligible and 59 patients were evaluable for response. One patient showed complete response (CR), 13 patients partial response (PR), 1 patient minor response (MR), 19 patients no change (NC) and 25 patients had progressive disease (PD). The overall response rate in 59 evaluable patients was 23.7% (95% CI = 13.6-36.6%). The primary tumor showed a 4.3% (1/23) response, while the metastatic lesions in the abdomen, pelvic mass, lung, liver, and lymph nodes showed response rates of 62.5% (5/8), 33.3% (1/3), 33.3% (1/3), 14.8% (4/27), and 13.9% (5/26), respectively. About hematological toxicity, severe (Grade 3 or more) leukopenia was observed in 36 patients (56.3%) and neutropenia in 52 patients (81.3%). Other major toxicity (Grade 3 or more) included nausea/vomiting in 11 patients (17.2%), anorexia in 9 patients (14.1%), fatigue in 5 patients (7.8%), and alopecia in 7 patients (10.9%), all which were tolerable. The results show that docetaxel is an effective anticancer agent for advanced/recurrent gastric cancer.

Adult↗
PubMed1998

[Phase I study of raltitrexed (ZD-1694)].

A multicenter cooperative phase I study of ZD-1694 (raltitrexed), a novel, folate-based thymidylate synthase (TS) inhibitor, was conducted with single and repeated doses in 30 patients with various malignant tumors. ZD-1694 was intravenously infused over 15 minutes. In the single-dose study, the initial dose was fixed at 1.0 mg/m2 (1n), and the dose was escalated stepwise up to 3.5 mg/m2 (3.5 n). Based on the results of the single-dose study, in the repeated-dose study, doses of 2.5 n and 3 n were infused every three weeks (3 weeks/one course). In principle, patients received 2 courses or more. Of the 29 eligible patients, 16 were in the single-dose study and 13 in the repeated-dose study. Adverse reactions were evaluated in all eligible patients. In the single-dose study, neutropenia, nausea/vomiting, diarrhea, and transaminase (GOT, GPT) increases, of grade 3 or higher, occurred at high doses of 3 n and 3.5 n. These were regarded as dose-limiting toxicities (DLT). DLT of grade 3 or higher were observed in 1 of 4 patients given 3 n and 2 of 4 patients given 3.5 n. These results suggested that the maximum tolerated dose (MTD) of ZD-1694 was 3.5 n (3.5 mg/m2). In the repeated-dose study, DLT of grade 3 or higher was observed in no more than one third of each dose group, 2 of the 6 patients given 2.5 n and 2 of the 7 patients given 3 n. These results suggested that 3 n (3.0 mg/m2), a dose nearer to MTD, was the recommended dose for the phase II study. Although transaminase increases were observed in all patients, in 12 of them the increase was grade 2 or lower and reversible. A pharmacokinetic investigation showed the mean elimination half life of ZD-1694 plasma concentration was 91.5 hours in the single-dose group and 119.1 hours in the repeated dose group. It was suggested that ZD-1694 is metabolized to polyglutamates after uptake and retained in the cells for a long duration. However, no accumulation was seen in plasma concentration of ZD-1694 following repeated doses at 3-weekly intervals. One PR was observed in a patient with colorectal cancer receiving 2.5 n in the repeated-dose study. Based on these results, the recommended dosage and administration for the phase II study of ZD-1694 was 3 n (3.0 mg/m2) intravenously infused over 15 minutes every 3 weeks.

Adult↗
PubMed1998

[Rehabilitation approach to children with sequelae of hypoxic encephalopathy].

We studied the rehabilitation approach to children with acquired hypoxic encephalopathy. The subjects were 13 children with sequelae of hypoxic encephalopathy. The onset ranged from 1 month to 15 years of age. Recovery was good in no case, moderate in 3, poor in 3, and absent in 7 cases. We evaluated the following factors: condition at the onset, present status, degree of improvement of the functional independence measure (FIM). In the moderate recovery group, resuscitation was performed within 5 minutes, and consciousness loss disappeared within 3 days. Some patients had no physical disability, whereas others had ataxia. In the no recovery group, consciousness loss was severe and continued more than 5 days. Most of them had spastic quadriplegia. The improvement of FIM was 52.8 +/- 23.9 in the moderate recovery group, 12.0 +/- 8.2 in the poor recovery group, and 0 in the no recovery group. Pediatricians as well as rehabilitation doctors should use FIM to evaluate the effect of rehabilitation.

Activities of Daily Living↗
PubMed1998

[Three patients with terminal gastric cancer who achieved good QOL through home hospice care].

In our G.I. department, patients with inoperable or recurrent cancer of the digestive organs are treated by chemotherapy and/or radiation therapy. Since the efficacy of these modalities has been poor in our hospital as in others, we have attempted to maintain good quality of life (QOL) in these patients by offering hospice care in the hospital or at home. Home care is provided to those who choose not to have chemotherapy or do not respond well to it. These patients live within 20 km of the hospital and are cared for at home by a visiting nurse or through visits to our outpatient clinic. However, in the latter patients who do not have access to good public transportation, clinic visits are a hardship to both patients and their families even though they do well with home hospice care. Home hospice care is also difficult for those who do not have adequate family support available. We report here three patients with terminal gastric cancer who appeared to experience good QOL through home hospice care.

Adult↗
PubMed1997

[Quality of life and chemotherapy in terminal stage of gastrointestinal cancers].

A patient in the terminal stage of gastrointestinal cancer is continuously worried by physical and psychological suffering, and asks for treatment to alleviate pain. We have conducted an assessment of the quality of life (QOL) in the terminal stage of cancer, and found a deterioration in active factor and total score of QOL 3 months before death. We have provided active chemotherapy in the terminal stage with the informed consent of the patient. The therapy has aimed at relieving suffering, prolonging survival and maintaining QOL.

Aged↗