Search PubMed⌕ Search

Biomedical subjects

K Matsunaga

Publications and source records attributed to K Matsunaga.

At least 73 records · Page 4Linked to original sources
PubMed2000

Epidemiologic investigation of the relative clearance of haloperidol by mixed-effect modeling using routine clinical pharmacokinetic data in Japanese patients.

The steady-state trough concentrations of haloperidol were studied to clarify the role of the characteristics of Japanese patients in estimating haloperidol dosing regimens by using routine therapeutic drug-monitoring data. Nonlinear mixed-effects modeling (NONMEM) was used to estimate the effect of a variety of developmental and demographic factors on haloperidol clearance values using 270 serum level measurements obtained from 191 patients during their clinical course. The final model describing haloperidol's relative clearance was CL = 0.74 x TBW(0.594) x DOSE(0.326) x 1.32CO1 x 0.867AGE, where CL is clearance (measured in liters per hour), TBW is the total body weight (in kilograms), DOSE is the daily dose of haloperidol (in grams per kilogram per day), CO1 = 1 for concomitant administration of antiepileptic drugs (phenobarbital, phenytoin, or carbamazepine) and CO1 = 0 otherwise, and AGE = 1 for patients aged 55 years or older and AGE = 0 otherwise. Concomitant administration of haloperidol and antiepileptic drugs resulted in a 32% increase in haloperidol clearance. Patients aged 55 years or older showed a 13.3% reduction in clearance values compared with the younger population.

Adolescent↗
PubMed2000

Expression of SART3 tumor-rejection antigen in gastric cancers.

We previously reported SART3 as a tumor-rejection antigen recognized by histocompatibility leukocyte antigen (HLA)-A24-restricted cytotoxic T lymphocytes (CTLs). In this study, we investigated the expression of the SART3 antigen in gastric cancers, as a candidate for use in specific immunotherapy. The SART3 antigen was detected in 9 of 10 (90%) gastric cancer cell lines, 35 of 52 (67.3%) gastric cancer tissues, and 0 of 20 non-tumorous gastric tissues. SART3-derived peptides corresponding to positions 109- 118 and 315-323 induced HLA-A24-restricted and tumor-specific CTLs from peripheral blood mononuclear cells (PBMCs) of gastric cancer patients. These peptide-induced CTLs recognized HLA-A24(+) SART3(+) gastric cancer cells, but not HLA-A24(+) SART3(-) or HLA-A24(-) SART3(+) gastric cancer cells. Therefore, the SART3 peptides could be useful in specific immunotherapy of gastric cancer patients.

Adenocarcinoma↗
PubMed2000

Differential effects of virulent versus avirulent Legionella pneumophila on chemokine gene expression in murine alveolar macrophages determined by cDNA expression array technique.

The cDNA expression array technique is a powerful tool to determine, at one time from many genes, specific gene messages modulated by infection. In the present study, we identified genes modulated in response to virulent versus avirulent Legionella pneumophila infection of the alveolar macrophage cell line MH-S by the cDNA expression array technique. Many macrophage genes were found to be modulated after 5 h of in vitro infection with L. pneumophila. In particular, it was found that the monocyte chemotactic protein 3 (MCP-3) gene expression was significantly induced by infection with virulent L. pneumophila but not with avirulent L. pneumophila. In contrast, other chemokine genes, such as macrophage inflammatory protein (MIP) 1alpha, were induced by both virulent and avirulent L. pneumophila. Reverse transcription (RT)-PCR assay of total RNA isolated from macrophages infected with the bacteria for 5 or 24 h confirmed the differential induction of the chemokine genes by virulent versus avirulent L. pneumophila. Thus, the cDNA expression array technique readily revealed differential induction by L. pneumophila infection of select chemokine genes of macrophages from more than 1,100 genes. These results also indicate that certain chemokine genes may be selectively induced by virulent bacteria.

Animals↗
PubMed2000

Nerve growth factor-potentiating compounds from Picrorhizae Rhizoma.

A crude methanol extract of Picrorhizae Rhizoma, the dried underground parts of Picrorhiza scrophulariiflora PENNELL, has been shown to potentiate the nerve growth factor (NGF)-induced neurite outgrowth from PC12D cells. The methanol extract was partitioned between ethyl acetate and water. The NGF-potentiating activity was observed in the ethyl acetate fraction. The ethyl acetate solubles were fractionated by silica gel chromatography, monitoring the NGF-potentiating activity to give two iridoid glycosides, picrosides I and II. Picrosides did not exhibit neurotrophic activity but caused a marked enhancement of the NGF-mediated neurite outgrowth from PC12D cells. The pharmacological data suggest that picrosides I and II enhance neurite outgrowth from PC12D cells, probably by amplifying a step in the NGF-receptor-mediated intracellular signaling pathway.

Animals↗
PubMed2000

[Hematological abnormalities of primary Sjogren's syndrome].

Sjogren's syndrome (SS) is an autoimmune disease characterized by a chronic inflammatory response mainly localized to the lacrimal and salivary glands. However, it sometimes involves extraglandular organs culminating in systemic disorders. Hematological abnormalities are not uncommon, although they rarely have clinical significance. In this study we examined 99 patients with primary SS who visited our hospital during 1989 to 1999. Patient's mean age was 54.1 years and 95 out of 99 were female. Lymphopenia and leukopenia was noted in 35 patients (35.3%) and 26 patients (26.2%) respectively, and 7 patients (7.1%) had thrombocytopenia. 43 patients (43.4%) had either of these hematological abnormalities. Patients with lymphopenia showed significantly low frequency of arthralgia and anti-SS-A/B antibody was more common in this group. Only one patient in this group required prednisolone therapy because of polyarthritis and general fatigue while others needed no specific therapy. Patients with thrombocytopenia were significantly younger and a male/female ratio was higher than those without this abnormality. They had higher tendency to accompany with skin eruption, positive anti-SS-B antibody, anti-nuclear antibody and rheumatoid factor. Three out of 8 patients with thrombocytopenia were treated with prednisolone according to the protocol for idiopathic thrombocytopenic purpura. All of 3 patients had positive PA-IgG and normocellular bone marrow. Autoimmune mechanism such as polyclonal B cell activation may play a role in the pathogenesis of thrombocytopenia.

Female↗
PubMed2000

Bisprasin, a novel Ca(2+) releaser with caffeine-like properties from a marine sponge, Dysidea spp., acts on Ca(2+)-induced Ca(2+) release channels of skeletal muscle sarcoplasmic reticulum.

Bisprasin, a unique bromotyrosine derivative containing a disulfide linkage, was isolated from a marine sponge of Dysidea spp. This compound caused a concentration-dependent (from 10 to 30 microM) increase in the (45)Ca(2+) release from the heavy fraction of skeletal muscle sarcoplasmic reticulum (HSR) of rabbit skeletal muscle in the same way as does caffeine. The 50% effective concentrations of bisprasin and caffeine were approximately 18 microM and 1.2 mM, respectively, indicating that the (45)Ca(2+)-releasing activity of bisprasin was approximately 70 times more potent than that of caffeine in HSR. The bell-shaped profile of Ca(2+) dependence for bisprasin was almost the same as that for caffeine. Typical blockers of Ca(2+)-induced Ca(2+) release channels, such as Mg(2+), procaine, and ruthenium red, inhibited markedly bisprasin- and caffeine-induced (45)Ca(2+) release from HSR. This compound, like caffeine, significantly enhanced [(3)H]ryanodine binding to HSR. Scatchard analysis of [(3)H]ryanodine binding to HSR revealed that bisprasin and caffeine decreased the K(D) value without affecting the B(max) value, suggesting that both the drugs facilitate the opening of ryanodine receptor channels. The bisprasin- and caffeine-induced increases in [(3)H]ryanodine binding were further enhanced by adenosine-5'-(beta, gamma-methylene)triphosphate. These results suggest that the pharmacological properties of bisprasin are almost similar to those of caffeine, except for its 70-fold higher potency. Here, we present the first report on the pharmacological properties of bisprasin, which, like caffeine, induces Ca(2+) release from skeletal muscle SR mediated through the ryanodine receptor.

Adenosine Triphosphate↗
PubMed2000

[Four cases with latex allergy followed by anaphylaxis to chestnut].

It is well known that patients with latex allergy have cross-reactions to various fruits, which is called a latex fruit syndrome. We report four cases with latex allergy followed by anaphylaxis to chestnut. They are all nurses of our hospital, who has personal history of atopic diseases. There were varieties in the methods of processing chestnut, presence of epicutaneous contact to chestnut, and clinical courses among the cases. All cases had positive skin prick test reactions while only two cases showed specific IgEs measured with AlaSTAT to chestnut. This fact suggests that we have to warn the risk of anaphylaxis even if one had not shown a serum specific IgE. We could follow the clinical courses and study specific IgEs to chestnut and latex in the two cases for more than two years. The titer of specific IgE was increased in the one, who could not avoid eating chestnut and contact to latex, while it was decreased in the other who could avoid the exposure to the antigens. Hevein is one of the panallergens among latex and related fruits. We studied specific IgEs to hevein on these four cases and 12 normal controls. The results showed that the former had significantly higher values of sIgEs to hevein compared to the latter (p < 0.05). We conclude that a patient with latex allergy has a high risk of contact urticaria or even anaphylaxis to the related fruits such as chestnut so that we recommend the patient with latex allergy to avoid them.

Adult↗
PubMed2000

[30 cases of occupational latex allergy].

We experienced 30 patients with occupational latex allergy (LA) in a 4-year period between 1995 and 1998 in Fujita Health University Hospital. All of them were medical personnel. We studied clinical symptoms and the clinical relevance of latex specific IgE and skin test (prick test and use test) in 30 cases. As a result, skin test result was most related of the diagnosis and the severity of LA. The average of the duration to decide LA diagnosis was 21.2 months. The reasons of the delayed diagnosis were that they were left and treated as an unexplained urticaria or asthma. Therefore, we have to warn about LA to the medical personnel who are frequently exposed to latex in Japan.

Adult↗
PubMed2000

Neonatal inoculation with the protein-bound polysaccharide PSK increases resistance of adult animals to challenge with syngeneic tumor cells and reduces azoxymethane-induced precancerous lesions in the colon.

We have investigated the results of neonatal inoculation with a protein-bound polysaccharide, PSK, as it affects the defense mechanism of animals against cancer. Male BALB/c mice received a single i.p. injection of 10 mg/kg PSK within 48 h of birth. When the mice were 8 weeks of age, colon adenocarcinoma 26 (C26 tumor) cells were transplanted s.c. Injection of PSK increased the number of tumor-rejecting mice from 10 to 50% compared with the control mice transplanted with 5 x 10(3) tumor cells and prolonged the median survival period to 174% of control mice with tumors. When the number of transplanted tumor cells was increased to 1 x 10(6), PSK injection significantly prolonged the survival period, although tumors grew in all mice. The survival period was also significantly prolonged in male C57BL/6 mice that received an injection neonatally with PSK and were given a s.c. transplant of Lewis lung carcinoma or B16 melanoma at 8 weeks of age. The effect on survival was dependent on the PSK dose and the number of transplanted tumor cells. PSK was as effective for male mice 30 weeks of age as for mice 8 weeks of age treated with PSK during the neonatal period. However, prolongation of the survival period of tumor-bearing mice was not observed in the offspring (F1). Neonatal injection of PSK also significantly reduced the number of metastatic foci in the liver of mice inoculated with 1 x 10(5) C26 tumor cells in the splenic vein after 8 weeks of age. In addition, neonatal injection of PSK significantly reduced the number of aberrant crypts and aberrant crypt foci, the precancerous lesions in the colon of F344 rats that received injections s.c. with azoxymethane after 7 weeks of age, to 47% of that of rats that received an injection with saline at the same age. The effect on precancerous lesions was dependent on the timing of PSK injection and the dose. Regarding the mechanism, when animals thymectomized during the neonatal period or when congenitally athymic animals were used instead of healthy animals, the effect on survival or precancerous lesions did not appear. Neonatal injection of PSK significantly reduced the number of CD4+ CD8+ T cells and significantly increased the number of CD4+ CD8- and CD4- CD8+ T cells in the thymus of healthy mice 10 weeks of age and C26 tumor-bearing mice. Furthermore, neonatal injection of PSK significantly elevated the T-cell differentiation induced by a mouse thymus extract 10 weeks of age. These findings suggest that neonatal injection of PSK induces resistance in adult mice to challenge by syngeneic tumor cells and reduces the azoxymethane-induced precancerous lesions in the colon of adult rats via the thymus functions.

Adenocarcinoma↗
PubMed2000

Use of fluoride-containing sealant on proximal surfaces.

A visible light curing sealant was developed for the prevention of caries on the smooth surfaces especially on the proximal surfaces. The sealant is mainly composed of dimethacrylate monomers. It contains a total amount of 2.28 mass% fluoride as poly(methyl methacrylate-co-methacryloyl fluoride) and sodium fluoride. The fluoride-containing sealant could be successfully applied to the proximal surfaces between the first and second primary molars by making access to the interproximal space with an orthodontic separating module. Availability of fluoride was assessed by the concentration of fluoride released into 1 ml of distilled water as a function of time from disks 5 mm in diameter and 0.2 mm in thickness. Ten microg of fluoride was measured on the first day; after 3 days the rate remained fairly constant at about 1 pg/day for a period of 28 days. The fluoride uptake and the improved acid solubility were investigated in vitro using bovine incisors. The fluoride of the control, that is enamel without sealant treatment, was not detectable. The fluoride incorporated into enamel after 37 hours application was 2,100 ppm at 2 pm from the enamel surface. The enamel solubility to acids decreased by the fluoride incorporation.

Animals↗
PubMed2000

Correlation in inorganic ion concentration between saliva and plaque fluid.

The composition and the concentration of inorganic ions in dental plaque significantly influence the initiation and the development of dental caries through altering the degree of saturation of the aqueous phase surrounding the dental enamel. In order to know how plaque is affected by saliva, the composition and the concentration of inorganic ions in saliva and plaque fluid were investigated. The ionic concentrations of sodium and chlorine had similar values between plaque fluid and saliva. However, the concentrations of the inorganic ions such as ammonium, potassium, magnesium, calcium, and phosphate were significantly different between plaque fluid and saliva. This meant that the saliva and plaque fluid were different in its inorganic composition presumably reflected by the metabolic activity of bacteria in the plaque. On the other hand, as for the correlation coefficients between plaque fluid and saliva composition, statistically significant correlation was observed in ions such as sodium, ammonium, potassium, magnesium, and chlorine but not in calcium, phosphate, or in pH values. This was possibly due to the fact that saliva was the main source of supply of these ions. However as for calcium and phosphate, no close correlation was found possibly because they could be supplied also through tooth enamel dissolution. The discrepancy of the results with former studies on this point was speculatively explained by,the difference of the plaque age used. It was considered reasonable that the pH value was independent, as it is mainly decided by the activity of the bacteria in the plaque.

Adult↗
PubMed1999

Expression of the tumor-rejection antigen SART1 in brain tumors.

We have reported a tumor-rejection antigen, SART1(259), possessing tumor epitopes capable of inducing cytotoxic T lymphocytes (CTLs) in epithelial-cancer patients. This study investigated the expression of SART1(259) antigen in brain tumors, to explore for a potential molecule for use in specific immunotherapy of patients with brain tumors. The SART1(259) antigen was detected in the cytosol fraction of 13 of 18 (72%) glioma cell lines and in 12 of 34 (35%) brain-tumor tissues, with a higher rate of expression among malignant gliomas (5/10, 50%) and schwannomas (3/4). HLA-A24-restricted and SART1-specific CTLs recognized the HLA-A24+ and SART1(259)+ glioma cells, and the levels of recognition correlated both with HLA-A24-antigen expression level and with the concentration of the SART1 peptide antigen. Therefore, the SART1(259) antigen could be a target molecule for specific immunotherapy of patients with brain tumors expressing HLA-class-1 antigens.

Antigens, Neoplasm↗
PubMed1999

Simultaneous measurement of volatile sulfur compounds using ascorbic acid for oxidant removal and gas chromatography-flame photometric detection.

A method for the simultaneous measurement of volatile sulfur compounds (COS, H2S, CS2, CH3SH, DMS) is established with preconcentration and GC-flame photometric detection (FPD). Prior to preconcentration of ambient air, it was necessary to remove SO2, water vapor and atmospheric oxidant. SO2 and water vapor were removed using a glass fiber filter and a cooled PTFE water trap loop, respectively. In order to remove atmospheric oxidant, the efficiency of an ascorbic acid scrubber was examined. It was found that an ascorbic acid scrubber enabled measurement of volatile sulfur compounds without adsorption and reaction loss. The detection limits for COS, H2S, CS2, CH3SH and DMS were 20, 34, 35, 263 and 44 pg of S, respectively.

Air↗
PubMed1999

Nardosinone, a novel enhancer of nerve growth factor in neurite outgrowth from PC12D cells.

We isolated nardosinone as a neuritogenic substance from Nardostachys chinensis. Nardosinone did not exhibit the neurotrophic activity but caused a marked enhancement of the nerve growth factor (NGF)-mediated neurite outgrowth from PC12D cells. Nardosinone-induced enhancement of the NGF-action was completely blocked by PD98059, a representative mitogen activated protein kinase (MAPK) kinase inhibitor. The microscopic observations indicated that the neurites in response to nardosinone and NGF were quite long and were generally extended to the neighboring cells. These results suggest that nardosinone enhances the NGF-induced neurite outgrowth from PC12D cells probably by amplifying an up-stream step of MAPK kinase in the NGF receptor-mediated intracellular signaling pathway.

Animals↗
PubMed1999

Properties of amentoflavone, a potent caffeine-like Ca2+ releaser in skeletal muscle sarcoplasmic reticulum.

Amentoflavone, like caffeine, caused a concentration-dependent increase in Ca2+ release from the heavy fraction of fragmented sarcoplasmic reticulum of rabbit skeletal muscle. The Ca2+ -releasing activity of amentoflavone was approximately 20 times more potent than that of caffeine. The bell-shaped profile of Ca2+ dependence for amentoflavone was almost the same as that for caffeine. Typical blockers of Ca2+ -induced Ca2+ release channels, such as Mg2+, procaine and ruthenium red, inhibited markedly amentoflavone- and caffeine-induced 45Ca2+ release. The maximum 45Ca2+ release in response to amentoflavone was not changed by caffeine, but was further increased by adenosine-5'-(beta,gamma-methylene) triphosphate. This compound enhanced [3H]ryanodine binding to the heavy fraction of fragmented sarcoplasmic reticulum with a decrease in K(D) but without a change in Bmax. These results suggest that amentoflavone, which does not contain a nitrogen atom, probably binds to the caffeine-binding site in Ca2+ channels and thus potentiates Ca2+ -induced Ca2+ release from the heavy fraction of fragmented sarcoplasmic reticulum.

Animals↗
PubMed1999

Identification of a SART-1-derived peptide capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes.

We have described the SART-1 gene-encoding peptides recognized by HLA-A2601-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). We now have investigated whether SART-1 encodes peptides capable of inducing the HLA-A24-restricted CTLs. Among the 18 different peptides with HLA-A24-binding motifs, the SART-1(690-698) peptide (EYRGFTQDF) was most strongly recognized by the HLA-A24-restricted and tumor-specific CTLs established from an esophageal cancer patient. After a third stimulation in vitro, this peptide induced HLA-A24-restricted CTLs recognizing the SART-1(259)+ tumor cells in PBMCs of all HLA-A24 homozygous and the majority of HLA-A24 heterozygous cancer patients and healthy donors tested. A similar activity, induction of CTLs from PBMCs, was observed in the Saccharomyces cerevisiae-derived nonapeptide (EYRGFTPMF) that shares 7 amino acids with the SART-1(690-698) peptide. The SART-1(690-698) peptide-induced CTL activity was significantly higher in PBMCs of HLA-A24 homozygotes than in HLA-A24 heterozygotes. The CTL precursor frequency in PBMCs after a third stimulation in vitro with the SART-1(690-698) peptide was high (>1/200) in both cancer patients and healthy donors. The SART-1(690-698) peptide could thus be useful for specific immunotherapy of HLA-A24+ cancer patients.

Antigens, Neoplasm↗