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Biomedical subjects

K Matsui

Publications and source records attributed to K Matsui.

At least 19 recordsLinked to original sources
PubMed2005

Phase I-II study of amrubicin and cisplatin in previously untreated patients with extensive-stage small-cell lung cancer.

BACKGROUND: Amrubicin, a totally synthetic 9-amino-anthracycline, demonstrated excellent single-agent activity for extensive-stage small-cell lung cancer (ED-SCLC). The aims of this trial were to determine the maximum-tolerated doses (MTD) of combination therapy with amrubicin and cisplatin, and to assess the efficacy and safety at their recommended doses (RD). PATIENTS AND METHODS: Eligibility criteria were patients having histologically or cytologically proven measurable ED-SCLC, no previous systemic therapy, an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Amrubicin was administered on days 1-3 and cisplatin on day 1, every 3 weeks. RESULTS: Four patients were enrolled at dose level 1 (amrubicin 40 mg/m(2)/day and cisplatin 60 mg/m(2)) and three patients at level 2 (amrubicin 45 mg/m(2)/day and cisplatin 60 mg/m(2)). Consequently, the MTD and RD were determined to be at level 2 and level 1, respectively. The response rate at the RD was 87.8% (36/41). The median survival time (MST) was 13.6 months and the 1-year survival rate was 56.1%. Grade 3/4 neutropenia and leukopenia occurred in 95.1% and 65.9% of patients, respectively. CONCLUSIONS: The combination of amrubicin and cisplatin has demonstrated an impressive response rate and MST in patients with previously untreated ED-SCLC.

Aged↗
PubMed2005

Percutaneous application of peptidoglycan from Staphylococcus aureus induces an increase in mast cell numbers in the dermis of mice.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. The dermis of lesional skin of AD patients shows an increased number of inflammatory cells such as mast cells, eosinophils and mononuclear cells and superficial Staphylococcus aureus colonization. OBJECTIVE: The purpose of this study was to determine the effects of peptidoglycan (PEG) from S. aureus on mast cell induction in murine skin. METHODS: PEG was applied to barrier-disrupted abdominal skin of mice every 5 days and the number of mast cells in the abdominal skin was counted 20 days after the first application. The cytokine response was investigated by RT-PCR and immunohistologic analysis. RESULTS: The number of mast cells in the skin of mice treated with PEG was increased significantly compared with that of mice given phosphate-buffered saline. In addition, application of PEG to the abdominal skin increased the expression of mRNA for transforming growth factor-beta(1) (TGF-beta(1)), which supports mast cell migration, but not that for IL-3 or stem cell factor, which support both mast cell proliferation and mast cell migration. Immunohistologic analysis demonstrated that levels of TGF-beta(1) transcripts corresponded with those of protein synthesis in the epidermis. TGF-beta(1) was found to be highly expressed in keratinocytes of the basal epidermis of PEG-treated skin. Furthermore, intraperitoneal injection of anti-TGF-beta(1) antibodies neutralized the induction of mast cells into the skin. CONCLUSION: These results suggest that PEG may have the ability to induce an increase in mast cell numbers in the skin through TGF-beta(1) production by epidermal keratinocytes. Skin inflammation might therefore be linked to colonization with S. aureus in AD patients.

Abdomen↗
PubMed2005

Daily inhibition of postprandial hyperglycaemia with JTT-608, a novel oral antidiabetic agent, ameliorates pancreatic function in neonatally streptozotocin-treated rats.

AIM: Chronic glycaemic control, in particular, the control of postprandial hyperglycaemia, is essential for preventing the development of diabetic complications. We therefore evaluated the chronic treatment effect of a new antidiabetic agent, JTT-608 [trans-4-(methylcyclohexyl)-4-oxobutyric acid], in neonatally streptozotocin-treated rats. METHODS: The rats were maintained with liquid meal three times a day and treated orally with JTT-608 10 min before each meal for 12 weeks. Haemoglobin A1C (HbA1C) and fasting blood glucose levels were measured at 4-week intervals, and effects of JTT-608 on pancreatic function and diabetic complications were examined after dosing period. RESULTS: The postprandial hyperglycaemia was suppressed by JTT-608 administration, and both HbA1C levels and fasting blood glucose levels were reduced during the experimental period. After the treatment period of 12 weeks, JTT-608 further improved the early insulin secretion and the impaired glucose tolerance after meal loading in the diabetic rats. Also, pathological examination revealed that JTT-608 reduced the incidence of the decrease in immunoreactivity of insulin. In examination of other diabetic complications, JTT-608 ameliorated the reduced motor nerve conduction velocities observed in diabetic rats and inhibited the incidence of cataracts with diabetes. CONCLUSIONS: We conclude that a newly developed antidiabetic agent, JTT-608, improves the pancreatic function and prevents the development of diabetic complications by inhibition of daily postprandial hyperglycaemia and could be useful for the treatment of diabetic subjects with impaired insulin secretion.

Animals↗
PubMed2005

Informed consent, participation in, and withdrawal from a population based cohort study involving genetic analysis.

OBJECTIVE: Population based cohort studies involving genetic research have been initiated in several countries. However, research published to date provides little information on the willingness of the general population to participate in such studies. Furthermore, there is a need to discover the optimal methods for acquiring fully informed consent from the general population. We therefore examined the results of a population based genetic cohort study to identify the factors affecting the participation rate by members of the general public and also specifically to examine the impact of different consent procedures on the rate of participation by prospective candidates and their subsequent withdrawal rate from the study. DESIGN: Descriptive analyses. SETTING AND PARTICIPANTS: The study evaluated two non-genetic subcohorts comprising 3166 people attending for a health checkup during 2002, and two genetic subcohorts comprising 2195 people who underwent a checkup during 2003. MAIN OUTCOME MEASUREMENTS: Analysis endpoints were differences in participation rates between the non-genetic and genetic subcohorts, differences between providing non-extensive and extensive preliminary information, and changes in participation status between baseline and at 6 months. RESULTS: Participation rates in the genetic subcohorts were 4.7-9.3% lower than those in the non-genetic subcohorts. The odds ratios (OR) of participation in genetic research were between 0.60 and 0.77, and the OR for withdrawal from the research was over 7.70; providing preliminary extensive information about genetic research reduced the withdrawal risks (OR 0.15 for all dependent variables) but worsened participation rates (OR 0.63-0.74). CONCLUSIONS: The general population responded sceptically towards genetic research. It is crucial that genetic researchers utilise an informative and educational consent process worthy of public trust.

Adolescent↗
PubMed2005

[Sternal metastasis of breast cancer; report of a case].

A 51-year-old woman presented with a painful sternal lump. Nine years earlier she had undergone right modified mastectomy for breast cancer, followed by chemotherapy. Computed tomography and bone scintigraphy demonstrated a solitary sternal bone metastasis. The patient was treated by partial sternectomy. Thereafter, the sternal defect was reconstructed with Marlex mesh and rectus abdominis myocutaneous flap. The postoperative course was uneventful. The patient subsequently developed brain metastasis and died within 52 months after sternal resection. The stability of the chest wall was well preserved for the duration of follow-up.

Bone Neoplasms↗
PubMed2004

Genes outside the S supergene suppress S functions in buckwheat (Fagopyrum esculentum).

BACKGROUND AND AIMS: Common buckwheat (Fagopyrum esculentum) is a dimorphic self-incompatible plant with either pin or thrum flowers. The S supergene is thought to govern self-incompatibility, flower morphology and pollen size in buckwheat. Two major types of self-fertile lines have been reported. One is a type with long-homostyle flowers, Kyukei SC2 (KSC2), and the other is a type with short-homostyle flowers, Pennline 10. To clarify whether the locus controlling flower morphology and self-fertility of Pennline 10 is the same as that of KSC2, pollen tube tests and genetic analysis have been performed. METHODS: Pollen tube growth was assessed in the styles and flower morphology of KSC2, Pennline 10, F1 and F2 plants that were produced by the crosses between plants with pin or thrum and Pennline 10. KEY RESULTS: Pollen tubes of Pennline 10 reached ovules of all flower types. The flower morphology of F1 plants produced by the cross between thrum and Pennline 10 were thrum or pin, and when pin plants were used as maternal plants, all the F1 plants were pin. Both plants with pin or short-pin flowers, whose ratio of style length to anther height was smaller than that of pin, appeared in F2 populations of thrum x Pennline 10 as well as in those of pin x Pennline 10. CONCLUSION: The results suggest that Pennline 10 possesses the s allele as pin does, not an allele produced by the recombination in the S supergene, and that the short style length of Pennline 10 is controlled by multiple genes outside the S supergene.

Crosses, Genetic↗
PubMed2004

Multi-institutional phase II trial of irinotecan, cisplatin, and etoposide for sensitive relapsed small-cell lung cancer.

Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). A multi-institutional phase II study was therefore conducted to evaluate the efficacy and toxicity of CPT-11 combined with cisplatin (CDDP) and etoposide (ETOP) (PEI regimen) for the treatment of sensitive relapsed SCLC. Patients who responded to first-line chemotherapy but relapsed more than 8 weeks after the completion of first-line therapy (n=40) were treated using the PEI regimen, which consisted of CDDP (25 mg m(-2)) weekly for 9 weeks, ETOP (60 mg m(-2)) for 3 days on weeks 1, 3, 5, 7, and 9, and CPT-11 (90 mg m(-2)) on weeks 2, 4, 6, and 8 with granulocyte colony-stimulating factor support. Five complete responses and 26 partial responses were observed, and the overall response rate was 78% (95% confidence interval 61.5-89.2%). The median survival time was 11.8 months, and the estimated 1-year survival rate was 49%. Grade 3/4 leucocytopenia, neutropenia, and thrombocytopenia were observed in 55, 73, and 33% of the patients, respectively. Nonhaematological toxicities were mild and transient in all patients. In conclusion, the PEI regimen is considered to be highly active and well tolerated for the treatment of sensitive relapsed SCLC.

Adult↗
PubMed2004

Randomised phase II study of docetaxel/cisplatin vs docetaxel/irinotecan in advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group Study (WJTOG9803).

Docetaxel plus cisplatin and docetaxel plus irinotecan are active and well-tolerated chemotherapy regimens for advanced non-small-cell lung cancer (NSCLC). A randomised phase II study compared their efficacy and toxicity in 108 patients with stage IIIb/IV NSCLC, who were randomised to receive docetaxel 60 mg m(-2) and cisplatin 80 mg m(-2) on day 1 (DC; n=51), or docetaxel 60 mg m(-2) on day 8 and irinotecan 60 mg m(-2) on day 1 and 8 (DI; n=57) every 3 weeks. Response rates were 37% for DC and 32% for DI patients. Median survival times and 1- and 2-year survival rates were 50 weeks (95% confidence interval: 34-78 weeks), 47 and 25% for DC, and 46 weeks (95% confidence interval: 37-54 weeks), 40 and 18% for DI, respectively. The progression-free survival time was 20 weeks (95% confidence interval: 14-25 weeks) with DC and 18 (95% confidence interval: 12-22 weeks) with DI. Significantly more DI than DC patients had grade 4 leucopenia and neutropenia (P<0.01); more DC patients had grade >/=2 thrombocytopenia (P<0.01). Nausea and vomiting was more pronounced with DC (P<0.01); diarrhoea was more common with DI (P=0.01). Three treatment-related deaths occurred in DC patients. In conclusion, although the DI and DC regimens had different toxicity profiles, there was no significant difference in survival.

Adult↗
PubMed2004

Expression of P450 aromatase protein in developing and in sex-reversed gonads of the XX/XY type of the frog Rana rugosa.

Gonadal differentiation in some species of amphibians is sensitive to steroids. The phenotypic sex of XX/XY-type frogs such as Rana rugosa can be reversed from female to male by injection of testosterone into tadpoles, but little is known about the molecular mechanism of this sex reversal. To elucidate the mechanism of the sex differentiation, we examined the role of P450 aromatase (P450arom), an enzyme that converts testosterone to estrogen, during gonadal differentiation of amphibians. In this study, we first cloned a P450arom cDNA homolog of the frog R. rugosa and analyzed by RT-PCR its expression profile in developing and in female-to-male sex-reversed gonads. P450arom expression was observed in the gonad of tadpoles during ovarian differentiation and became much stronger in the developing ovary in which only immature oocytes were observed. However, its expression declined significantly in the ovary of frogs 2 months after metamorphosis, when oocytes were growing; and it was no longer seen in adult ovaries. By RT-PCR, we also examined the expression of P450arom and SF-1 (steroidogenic factor-1; the orphan nuclear receptor) in the female-to-male sex-reversed gonad. The level of P450arom mRNA was high in the ovary, but it declined rapidly after the injection of testosterone. In contrast, no change in the SF-1 (also known as Ad4BP) expression was observed. Moreover, to identify the type(s) of cells expressing P450arom protein, we performed immunostaining with an antibody against frog P450arom protein. Cells giving positive signals were observed around oocytes in the ovary of frogs 1 month after metamorphosis. They were identified as follicle cells by both light and electron microscopy. The results, taken together, indicate that P450arom protein is synthesized in follicle cells and that P450arom is very much involved in ovarian differentiation in R. rugosa.

Amino Acid Sequence↗
PubMed2004

Association between patient education and health-related quality of life in patients with Parkinson's disease.

BACKGROUND: Providing patients with disease- and treatment-related information is an important role of medical staff and is now reimbursed in Japan by the national health insurance system under the rubric 'patient education'. Evaluation of the effectiveness of patient education programs is necessary to ensure that limited health care resources are used efficiently. OBJECTIVE: The objective is to determine whether educating patients with Parkinson's disease (PD) is related to better health-related quality of life (HRQOL). DESIGN: A cross-sectional study was conducted. SETTING: Members of the Japan Association of Patients with Parkinson's disease were randomly selected. PARTICIPANTS: A total of 1200 patients with PD were asked to fill in written questionnaires and replies from 762 (63.5%) were analyzed. MEASUREMENTS: The questionnaire inquired about clinical characteristics, comorbidity, symptoms of PD, complications of therapy, HRQOL, and patient education. SF-36 was used to assess HRQOL. The section on patient education comprised one question each on patient-perceived satisfaction with information provided on (1) disease condition and pathophysiology, (2) effectiveness of drug therapy, (3) adverse drug reactions, (4) publicly available financial and social resources, and (5) rehabilitation and daily activities. Patient education score was defined as the sum of the individual scores for these five questions. The relationships between scores on the SF-36 subscales and the patient education score were examined. RESULTS: More satisfaction with patient education was associated with higher scores in all SF-36 subscales except physical functioning and bodily pain. The difference in score between the most satisfied and the least satisfied patients ranged from 8.4 points on the subscales of general health and 16.7 points on the subscale of role limitation due to emotional problems. CONCLUSION: The conclusion that patient education is associated with better HRQOL in patients with PD is drawn.

Aged↗
PubMed2004

Identification of AFLP makers linked to non-seed shattering locus (sht1) in buckwheat and conversion to STS markers for marker-assisted selection.

Shattering habit in buckwheat has two forms: brittle pedicel and weak pedicel. Brittle pedicel is observed in wild buckwheat, but not in cultivated buckwheat. Brittle pedicel in buckwheat is produced by two complementary, dominant genes, Sht1 and Sht2. The sht1 locus is linked to the S locus; almost all common buckwheat cultivars possess the allele sht1. To detect molecular makers linked to the sht1 locus, we used amplified fragment-length polymorphism (AFLP) analysis in combination with bulked segregant analysis of segregating progeny of a cross between a non-brittle common buckwheat and a brittle self-compatible buckwheat line. We screened 312 primer combinations and constructed a linkage map around the sht1 locus by using 102 F2 plants. Five AFLP markers were linked to the sht1 locus. Two of these, e54m58/610 and e55m46/320, cosegregated with the sht1 locus without recombination. The two AFLP markers were converted to STS markers according to the sequence of the AFLPs. The STS markers are useful for marker-assisted selection of non-brittle pedicel plants and provides a stepping-stone for map-based cloning and characterization of the gene encoding non-brittle pedicel.

Base Sequence↗
PubMed2003

Lipoteichoic acid from Staphylococcus aureus enhances allergen-specific immunoglobulin E production in mice.

BACKGROUND: Our previous study demonstrated that lipoteichoic acid (LTA) from Staphylococcus aureus induced T helper type 2 (Th2)-prone dermatitis resembling that seen in atopic dermatitis (AD) patients in mice sensitized percutaneously with an allergen. However, the effects of LTA on allergen-specific IgE production in such sensitized mice have not been elucidated. OBJECTIVE: The purpose of this study was to determine the effects of LTA from S. aureus on allergen-specific IgE production in mice sensitized percutaneously with a house dust mite antigen (MA). METHODS: Mice were sensitized with a single topical application of MA and/or LTA to barrier-disrupted abdominal skin. One to 5 weeks later, MA-specific IgE antibodies in sera from sensitized mice were detected by an enzyme-linked immunosorbent assay (ELISA). Expression of B7.1 (CD80), B7.2 (CD86) and CD40L molecules by CD40-positive (CD40+) and CD4-positive (CD4+) cells in the lymph nodes of sensitized mice were analysed by flow-cytometry (FACS). RESULTS: Simultaneous sensitization with MA and LTA increased IgE production 3 weeks later, significantly more than sensitization with MA alone. FACS analysis of CD40+ cells in the lymph nodes from sensitized mice showed that simultaneous sensitization with MA and LTA did not enhance CD80- or CD86-expression by antigen-presenting cells such as B lymphocytes and dendritic cells more than sensitization with MA alone. However, analysis of CD4+ cells in the lymph nodes showed that simultaneous sensitization with MA and LTA increased the number of CD40L-expressing Th cells more than sensitization with MA alone. CONCLUSION: These results suggest that LTA enhances allergen-specific IgE production by a mechanism associated with up-regulation of CD40L-expressing Th cells and this might explain the role of skin colonization with S. aureus in AD patients.

Allergens↗
PubMed2003

Randomized phase II study of cisplatin, irinotecan and etoposide combinations administered weekly or every 4 weeks for extensive small-cell lung cancer (JCOG9902-DI).

BACKGROUND: The purpose of this study was to evaluate the toxicity and antitumor effect of cisplatin, irinotecan and etoposide combinations on two schedules, arms A and B, for previously untreated extensive small-cell lung cancer (E-SCLC), and to select the right arm for phase III trials. PATIENTS AND METHODS: Sixty patients were randomized to receive either arm A (cisplatin 25 mg/m(2) day 1, weekly for 9 weeks, irinotecan 90 mg/m(2) day 1, on weeks 1, 3, 5, 7 and 9, and etoposide 60 mg/m(2) days 1-3, on weeks 2, 4, 6, 8), or arm B (cisplatin 60 mg/m(2) day 1, irinotecan 60 mg/m(2) days 1, 8, 15, and etoposide 50 mg/m(2) days 1-3, every 4 weeks for four cycles). Prophylactic granulocyte colony-stimulating factor support was provided in both arms. RESULTS: Full cycles were delivered to 73% and 70% of patients in arms A and B, respectively. Incidences of grade 3-4 neutropenia, anemia, thrombocytopenia, infection and diarrhea were 57, 43, 27, 7 and 7%, respectively, in arm A, and 87, 47, 10, 13 and 10%, respectively, in arm B. A treatment-related death developed in one patient in arm A. Complete and partial response rates were 7% and 77%, respectively, in arm A, and 17% and 60%, respectively, in arm B. Median survival time was 8.9 months in arm A, and 12.9 months in arm B. CONCLUSIONS: Arm B showed a promising complete response rate and median survival with acceptable toxicity in patients with E-SCLC, and should be selected for the investigational arm in phase III trials.

Aged↗
PubMed2003

Expression of Dmrt1 protein in developing and in sex-reversed gonads of amphibians.

Many genes are known to be involved in gonadal differentiation in vertebrates. Dmrt1, a gene that encodes a transcription factor with a DM-domain, is considered to be one of the essential genes controlling testicular differentiation in mammals, birds, reptiles, amphibians and fish. However, it still remains unknown which testicular cells of animals other than mice and chicks express Dmrt1 protein. For an explanation of its role(s) in testicular differentiation in vertebrates, the expression of the Dmrt1 protein needs to be studied. For this purpose, we conducted an immunohistochemical study of this protein in an amphibian by using an antibody specific for Dmrt1. No positive signal was found in the indifferent gonad of tadpoles of Rana rugosa at early stages. However, in the testis of tadpoles at later stages (XV-XXV) and in frogs one month after metamorphosis, this protein was expressed in interstitial cells and Sertoli cells. In the testis of adult frogs, germ cells also expressed Dmrt1 protein. RT-PCR analysis revealed that the gene for this protein was not transcribed at any time during ovarian development, but was expressed in the female to male sex-reversed gonad. This was true when immunohistological studies were performed. In addition, Southern blot analysis showed DMRT1 to be an autosomal gene. Taken together, our findings indicate that Dmrt1 protein is expressed by interstitial cells, Seroli cells and germ cells in the testis of R. rugosa. Dmrt1 may thus be very involved in the testicular differentiation of amphibians.

Animals↗
PubMed2002

Lipoteichoic acid from Staphylococcus aureus induces Th2-prone dermatitis in mice sensitized percutaneously with an allergen.

BACKGROUND: We found previously that lipoteichoic acid (LTA) from Staphylococcus aureus has the ability to induce Th2 cytokine production by peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD). However, it is not known whether LTA can induce a Th2-dominant cytokine response in the skin of AD patients. OBJECTIVE: The purpose of this study was to determine the effects of LTA in mice sensitized percutaneously with a house dust mite antigen (MA) through barrier-disrupted skin, as an experimental animal model of AD. METHODS: Mice were sensitized with MA by a single topical application to barrier-disrupted abdominal skin. Seven days after the sensitization, the mice were challenged on the dorsal skin by LTA to elicit localized skin inflammation. The cytokine response in the dorsal skin was investigated by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistological analysis. The infiltration of inflammatory cells in the skin was also observed by histological staining. RESULTS: Injection of LTA into the dorsal skin of MA-sensitized mice, which show a Th2-dominant cytokine response against the homologous antigen, increased the expression of mRNA for IFN-gamma, IL-4 and IL-5, but not IL-2. Immunohistological analysis demonstrated that levels of IFN-gamma, IL-4 and IL-5 transcripts corresponded with those of protein synthesis. In addition, the dorsal skin of MA-sensitized mice challenged with LTA showed significantly increased numbers of neutrophils, eosinophils, mononuclear cells and mast cells compared with control mice challenged with LTA. CONCLUSION: These results suggest that LTA has the ability to induce localized Th2-prone dermatitis in an allergen-independent manner in the skin of AD patients and may explain the role of colonization with S. aureus in AD patients.

Allergens↗