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Biomedical subjects

K Matsushita

Publications and source records attributed to K Matsushita.

At least 19 recordsLinked to original sources
PubMed2007

Roxithromycin inhibits tumor necrosis factor-alpha-induced matrix metalloproteinase-1 expression through regulating mitogen-activated protein kinase phosphorylation and Ets-1 expression.

BACKGROUND AND OBJECTIVE: In periodontitis, matrix metalloproteinases (MMPs) are upregulated in response to locally released inflammatory cytokines, resulting in pathologic processes. Roxithromycin is a 14-membered ring macrolide antibiotic with broad-spectrum antibacterial effects against oral pathogens and immunomodulatory effects. Recently, we reported that roxithromycin inhibits tumor necrosis factor (TNF)-alpha-induced vascular endothelial growth factor expression in human periodontal ligament (HPDL) cell cultures. In the present study, we examined the effect of roxithromycin on TNF-alpha-induced MMP-1 production by HPDL cells. MATERIAL AND METHODS: Cultured cells were incubated with 1% fetal bovine serum for 24 h, followed by treatment with 10 ng/ml TNF-alpha, 10 microM roxithromycin, and mitogen-activated protein kinase inhibitor at various concentrations. Culture supernatants and sediments were collected at different time-points and used for enzyme-linked immunosorbent assays, and northern and western blot analyses. RESULTS: In HPDL cell cultures, roxithromycin strongly inhibited TNF-alpha-induced MMP-1 mRNA expression and production. The inhibition of MMP-1 gene expression by roxithromycin was dependent on de novo protein synthesis and was regulated at the transcriptional level. Roxithromycin significantly inhibited TNF-alpha-induced c-Jun N-terminal kinase activation (JNP) and marginally inhibited extracellular signal-regulated kinase (ERK) 1/2 activation, but not p38 mitogen-activated protein kinase activation. Furthermore, roxithromycin reduced the induction of Ets-1, one of the critical factors in MMP-1 transcription. CONCLUSION: Roxithromycin inhibits TNF-alpha-mediated MMP-1 induction through the downregulation of ERK1/2 and JNK activation and the subsequent reduction of Ets-1, suggesting that roxithromycin may have therapeutic use in periodontitis and other chronic inflammatory conditions involving MMP-1 induction.

Adult↗
PubMed2006

Arginine-specific gingipains from Porphyromonas gingivalis deprive protective functions of secretory leucocyte protease inhibitor in periodontal tissue.

Chronic periodontitis is correlated with Porphyromonas gingivalis infection. In this study, we found that the expression of secretory leucocyte protease inhibitor (SLPI), an endogenous inhibitor for neutrophil-derived proteases, was reduced in gingival tissues with chronic periodontitis associated with P. gingivalis infection. The addition of vesicles of P. gingivalis decreased the amount of SLPI in the media of primary human gingival keratinocytes compared to untreated cultures. We therefore investigated how arginine-specific gingipains (Rgps) affect the functions of SLPI, because Rgps are the major virulence factors in the vesicles and cleave a wide range of in-host proteins. We found that Rgps digest SLPI in vitro, suppressing the release of SLPI. Rgps proteolysis of SLPI disrupted SLPI functions, which normally suppresses neutrophil elastase and neutralizes pro-inflammatory effects of bacterial cell wall compounds in cultured human gingival fibroblasts. The protease inhibitory action of SLPI was not exerted towards Rgps. These results suggest that Rgps reduce the protective effects of SLPI on neutrophil proteases and bacterial proinflammatory compounds, by which disease in gingival tissue may be accelerated at the sites with P. gingivalis infection.

Adhesins, Bacterial↗
PubMed2006

Lack of alpha2-antiplasmin improves cutaneous wound healing via over-released vascular endothelial growth factor-induced angiogenesis in wound lesions.

BACKGROUND: The fibrinolytic system is supposed to play an important role in the degradation of extracellular matrices for physiological and pathological tissue remodeling; however, the detailed mechanism regarding how this system affects cutaneous wound healing remains to be clarified. METHODS AND RESULTS: We performed experimental cutaneous wounding in mice with a deficiency of alpha(2)-antiplasmin (alpha(2)AP), which is a potent and specific plasmin inhibitor. We found that an accelerated wound closure was observed in alpha(2)AP-deficient (alpha(2)AP-/-) mice in comparison with wild type (WT) mice. Moreover, we observed that a greater increase of angiogenesis occurred in the process of wound healing in alpha(2)AP-/- mice than in the WT mice. Intriguingly, mRNA expression of vascular endothelial growth factor (VEGF), which is the best characterized positive regulator of angiogenesis, in wound lesions was found to show a greater increase in the early phase of the healing process in alpha(2)AP-/- mice than in WT mice. In addition, the amount of released-VEGF from the explanted fibroblasts of alpha(2)AP-/- mice increased dramatically more than in the WT mice. Finally, the intra-jugular administration of anti-VEGF antibody clearly suppressed the increased angiogenesis and accelerated wound closure in the wound lesion of alpha(2)AP-/- mice. CONCLUSION: The lack of alpha(2)AP markedly causes an over-release of VEGF from the fibroblasts in cutaneous wound lesions, thereby inducing angiogenesis around the area, and thus resulting in an accelerated-wound closure. CONCLUSIONS: This is the first report to describe the crucial role that alpha(2)AP plays following angiogenesis in the process of wound healing. Our results provide new insight into the role of alpha(2)AP on cutaneous wound healing.

Animals↗
PubMed2006

[Surgical therapy for impalpable small lung lesion; confirmation method by means of combining computed tomography (CT)-guided marking with soft X-ray radiography].

OBJECTIVE: We examined the usefulness of soft X-ray radiography of the specimen which was obtained by the lung wedge biopsy. PATIENTS AND METHODS: From September 2002 to September 2005, we entered the 10 cases (5 men and 5 women) which were consisted of 15 lesions. We performed lung wedge biopsy after computed tomography (CT)-guided lung marking, and then confirmed the lesion in the specimen by means of soft X-ray radiography. RESULTS: We could confirm impalpable small lung lesions in all cases. CONCLUSION: The confirmation method of impalpable small lung lesion that combined CT-guided lung marking with soft X-ray radiography was very useful.

Adenomatosis, Pulmonary↗
PubMed2006

[Lung cancer with a cystic lesion formed by the check-valve mechanism].

A 55-year-old man was admitted to our hospital with a growing cystic lesion in the left middle field of the lung. After we diagnosed it as non-small cell lung cancer, we performed left upper lobectomy. A series of chest X-ray revealed that the cyst was formed by the check-valve mechanism due to the lung cancer, retrospectively. We should keep in mind the existence of lung cancer and other malignant tumors adjacent to cystic lesions.

Adenocarcinoma↗
PubMed2005

Validity of self-reported height and weight in a Japanese workplace population.

OBJECTIVE: To assess the validity of self-reported height and weight in a Japanese workplace population, and to examine factors associated with the validity of self-reported weight. DESIGN: Comparison of self-reported height and weight with independent measurement. SUBJECTS: In total, 4253 men and 1148 women aged 35-64 y (mean measured body mass index (BMI): 23.3 kg/m(2) in men, 21.9 kg/m(2) in women) were included in the study. MEASUREMENTS: Self-reported height and weight were obtained by a self-administered questionnaire. Measured height and weight were based on annual health checkups. Sex, age, measured BMI, and the presence of hypertension, diabetes, and hyperlipidemia were examined as potential factors associated with the accuracy of self-reported weight. RESULTS: Self-reported height and weight were highly correlated with measured height and weight for men and women (Pearson's r for men and women: 0.979 and 0.988 in height, 0.961 and 0.959 in weight, 0.943 and 0.950 in BMI, respectively). For men, mean differences+/-2 s.d. of height and weight were 0.078+/-2.324 cm and -0.034+/-5.012 kg, respectively, and for women 0.029+/-1.652 cm and 0.024+/-4.192 kg, respectively. The prevalence of obesity with BMI > or =25 kg/m(2) based on self-reported data (23.6 and 11.5% for men and women, respectively) was slightly smaller than that based on measured data (24.9 and 12.4%, respectively). Specificity and sensitivity, however, were quite high for both men and women (sensitivity was 85.8 and 85.2%, and specificity was 97.0 and 98.9%, respectively). The subjects with higher measured BMI significantly underestimated their weight compared with those with smaller BMI after adjustments for age in men and women. Furthermore, the presence of diabetes in men and age in women affected self-reported weight. Neither the presence of hypertension nor hyperlipidemia was associated with reporting bias. CONCLUSION: The self-reported height and weight were generally reliable in the middle-aged employed Japanese men and women. However, it should be remembered that self-reported weight was biased by actual BMI and affected by age and the presence of diabetes.

Adult↗
PubMed2005

Normalization of reversed bio-intact-PTH(1-84)/intact-PTH ratio after parathyroidectomy in a patient with severe secondary hyperparathyroidism.

The conventional intact-PTH assay detects both (1-84)-PTH and C-terminal fragments. The newer PTH assays, bio-intact-PTH assay and whole-PTH assay, use an antibody that binds only if the first amino acid is present, making it specific for the complete molecule, (1-84)-PTH. Thus, the intact-PTH concentrations are theoretically higher than bio-intact-PTH concentrations, and the ratio of bio-intact-PTH/intact-PTH is usually less than 1. These findings are observed in normal subjects and patients with primary and secondary hyperparathyroidism. Here we present a hemodialysis patient with severe secondary hyperparathyroidism who was found to have abnormally higher plasma bio-intact-PTH concentrations than intact-PTH concentrations, and the abnormally high biointact-PTH/intact-PTH ratio improved after parathyroidectomy (PTx). The patient was a 67-year-old man on maintenance hemodialysis since 1995. Since 2003, he was found to have high plasma intact-PTH concentrations and two swollen parathyroid glands in the neck. PTx with forearm autograft was performed in October 2003. Before PTx, an abnormally high ratio of bio-intact-PTH/intact-PTH was detected (840 pg/ml/770 pg/ml, > 1), while the same ratio was improved to normal range (100 pg/ml/200 pg/ml, < 1). Recently, a few patients with parathyroid carcinoma have been found to have higher (1-84)-PTH concentrations than intact-PTH concentrations with abnormally high (1-84)-PTH/intact-PTH ratio. Moreover, a new molecular form of PTH distinct from (1-84)-PTH was detected in these patients. We speculate that the resected parathyroid gland in our patient might have produced a new molecular form of PTH that was less well detected by the conventional intact-PTH assay.

Aged↗
PubMed2005

Identification of Fabry's disease by the screening of alpha-galactosidase A activity in male and female hemodialysis patients.

BACKGROUND: Although previous studies reported that the prevalence of Fabry's disease was 0.16 - 1.2% in hemodialysis (HD) patients based on measurement of a-galactosidase A (alpha-Gal A) activity, few reports detected female patients by the screening for alpha-Gal A. Here we determined the prevalence of Fabry's disease not only in male but also in female HD patients by measuring alpha-Gal A. METHODS: Plasma alpha-Gal A was measured in 696 consecutive males (n = 401) and females (n = 295) on HD. Patients with low plasma alpha-Gal A were examined for leukocyte alpha-Gal A, and patients with low leukocyte alpha-Gal A underwent alpha-Gal A gene sequence analysis for possible mutations, and family survey. RESULTS: Among 15 patients with low plasma alpha-Gal A activity, 4 male patients with low leukocyte alpha-Gal A and 1 female patient revealing low plasma alpha-Gal A were detected in 696 HD patients (0.7% of total patients). 3 of these 5 patients were already diagnosed to have the classical type of Fabry's disease. The other 2 patients were newly diagnosed as Fabry's disease, and did not have typical manifestations of Fabry's disease other than renal failure and left ventricular hypertrophy. DNA analysis of these 2 newly diagnosed patients revealed that each had an alpha-Gal missense mutation, previously identified (E66Q, M2961). CONCLUSION: Fabry's disease should be considered in the etiology of unexplained end-stage renal disease. Not only affected males but also affected females undergoing HD patients can be readily diagnosed by alpha-Gal A activities and gene analysis. These patients and their family members may benefit from enzyme replacement therapy for Fabry's disease.

Adult↗
PubMed2005

[Non-small cell lung cancer simultaneously metastatic to the brain treated by lobectomy and stereotactic irradiation].

We performed left upper lobectomy in 64-year-old man with non-small cell lung cancer (NSCLC) simultaneously metastatic to the brain. He was treated by stereotactic irradiation (STI) 2 months later after lobectomy. He has been doing well now without recurrence for 5 years after the operation. We think that STI and radical lobectomy are good alternatives for patients with NSCLC metastatic to the brain.

Brain Neoplasms↗
PubMed2004

D-hexosaminate production by oxidative fermentation.

Microbial production of D-hexosaminate was examined by means of oxidative fermentation with acetic acid bacteria. In most strains of acetic acid bacteria, membrane-bound D-glucosamine dehydrogenase (synonymous with an alternative D-glucose dehydrogenase distinct from quinoprotein D-glucose dehydrogenase) oxidized D-hexosamines to the corresponding D-hexosaminates in a stoichiometric manner. Conversion of D-hexosamines to the corresponding D-hexosaminates was observed with growing cells of acetic acid bacteria, and D-hexosaminate was stably accumulated in the culture medium even though D-hexosamine was exhausted. Since the enzyme responsible is located on the outer surface of the cytoplasmic membrane, and the enzyme activity is linked to the respiratory chain of the organisms, resting cells, dried cells, and immobilized cells of acetic acid bacteria were effective catalysts for D-hexosaminate production. D-Mannosaminate and D-galactosaminate were also prepared for the first time by means of oxidative fermentation, and three different D-hexosaminates were isolated from unreacted substrate by a chromatographic separation. In this paper, D-hexosaminate production by oxidative fermentation carried out mainly with Gluconobacter frateurii IFO 3264 is exemplified as a typical example.

Acetobacter↗
PubMed2004

Time course of gene expression after the injection of adenoviral vectors containing CTLA4IG gene.

INTRODUCTION: In vivo gene transfection using a recombinant adenoviral vector leads to diminished gene expression in a time-dependent manner that disappears within 4 weeks. CTLA4Ig blocks CD28-mediated costimulatory signal, and inhibits immune responses. We investigated the duration of transgene expression after administration of adenoviral vector containing CTLA4Ig gene (AdCTLA4Ig). METHODS: We injected 1 x 10(9) plaque forming units (pfu) of AdCTLA4Ig into rats (n = 7) via the tail vein. Thereafter, the blood samples were collected for assay of serum CTLA4Ig levels using enzyme-linked immunosorbent assay. RESULTS: The CTLA4Ig level reached the maximum (range, 65-86 microg/mL; average, 75 microg/mL) on days 3 to 5 after injection. Detectable levels of CTLA4Ig were observed up to 49 days. When we injected AdCTLA4Ig in combination with FTY720 administration, the maximum levels were higher and the detectable levels persisted longer. CONCLUSIONS: Because directly injected adenoviral transgene expression had been reported to disappear between 21 to 30 days, we conclude that AdCTLA4Ig inhibits the immune response and prolongs the transgene (CTLA4Ig gene) expression. Some additional immunosuppressants, like FTY720, may be useful to enhance AdCTLA4Ig effects.

Abatacept↗
PubMed2004

[Thoracoscopically resected cystic mediastinal hemangioma; report of a case].

An asymptomatic 66-year-old female was admitted because of an abnormal shadow on chest X-ray. Computed tomography (CT) revealed that a well-marginated round mass with low density, about 3 cm in diameter, was located in the right anterior superior mediastinum. The border was partially enhanced at contrast material-enhanced CT. Magnetic resonance imaging (MRI) [T 2-weighted] showed the lesion as a high intensity tumor. We performed thoracoscopic surgery and resected the easy-bleeding tumor completely. The tumor was dark red in color and contained old blood. The histopathological diagnosis was hemangioma. There was no recurrence for 3 years. Hemangiomas should be considered in the differential diagnosis of well-marginated masses. Thoracoscopic surgery is the very useful methods to resect the mediastinal hemangioma.

Aged↗
PubMed2004

[Thoracoscopically diagnosed multicentric Castleman disease; report of a case].

A 57-year-old female was admitted because of chest and back pain. Computed tomography (CT) revealed that many well-marginated lymph nodes were located in mediastinum and abdominal para-aortic area, especially in the right lower mediastinum. These lymph nodes were enhanced at contrast material-enhanced CT. We performed thoracoscopic surgery. The histopathologic diagnosis was multicentric Castleman disease (MCD). MCD should be considered in the differential diagnosis of multiple lymph nodes swelling with hyper globulinemia. Thoracoscopic surgery is the useful method to resect the lymph nodes and diagnose MCD.

Adult↗
PubMed2003

Mechanical compression of the extracranial vertebral artery during neck rotation.

Using duplex ultrasonography (US), the authors showed compression of the extracranial vertebral artery (ECVA) during neck rotation in 5.0% of 1,108 patients. Age (per 10-year increase, OR 0.80, 95% CI 0.67 to 0.96), vessel diameters (per 0.5-mm diameter increase, OR 0.63, 95% CI 0.51 to 0.79), and symptoms upon neck rotation (OR 4.01, 95% CI 1.35 to 11.9) were associated with vessel compression. In one case, SPECT revealed decreased cerebral perfusion of the hindbrain during rotation. ECVA US is useful in identifying vessel compression, especially in patients with symptoms on neck rotation.

Aged↗
PubMed2003

New quinoproteins in oxidative fermentation.

Several quinoproteins have been newly indicated in acetic acid bacteria, all of which can be applied to fermentative or enzymatic production of useful materials by means of oxidative fermentation. (1) D-Arabitol dehydrogenase from Gluconobacter suboxydans IFO 3257 was purified from the bacterial membrane and found to be a versatile enzyme for oxidation of various substrates to the corresponding oxidation products. It is worthy of notice that the enzyme catalyzes D-gluconate oxidation to 5-keto-D-gluconate, whereas 2-keto-D-gluconate is produced by a flavoprotein D-gluconate dehydrogenase. (2) Membrane-bound cyclic alcohol dehydrogenase was solubilized and purified for the first time from Gluconobacter frateurii CHM 9. When compared with the cytosolic NAD-dependent cyclic alcohol dehydrogenase crystallized from the same strain, the reaction rate in cyclic alcohol oxidation by the membrane enzyme was 100 times stronger than the cytosolic NAD-dependent enzyme. The NAD-dependent enzyme makes no contribution to cyclic alcohol oxidation but contributes to the reduction of cyclic ketones to cyclic alcohols. (3) Meso-erythritol dehydrogenase has been purified from the membrane fraction of G. frateurii CHM 43. The typical properties of quinoproteins were indicated in many respects with the enzyme. It was found that the enzyme, growing cells and also the resting cells of the organism are very effective in producing L-erythrulose. Dihydroxyacetone can be replaced by L-erythrulose for cosmetics for those who are sensitive to dihydroxyacetone. (4) Two different membrane-bound D-sorbitol dehydrogenases were indicated in acetic acid bacteria. One enzyme contributing to L-sorbose production has been identified to be a quinoprotein, while another FAD-containing D-sorbitol dehydrogenase catalyzes D-sorbitol oxidation to D-fructose. D-Fructose production by the oxidative fermentation would be possible by the latter enzyme and it is superior to the well-established D-glucose isomerase, because the oxidative fermentation catalyzes irreversible one-way oxidation of D-sorbitol to D-fructose without any reaction equilibrium, unlike D-glucose isomerase. (5) Quinate dehydrogenase was found in several Gluconobacter strains and other aerobic bacteria like Pseudomonas and Acinetobacter strains. It has become possible to produce dehydroquinate, dehydroshikimate, and shikimate by oxidative fermentation. Quinate dehydrogenase was readily solubilized from the membrane fraction by alkylglucoside in the presence of 0.1 M KCl. A simple purification by hydrophobic chromatography gave a highly purified quinate dehydrogenase that was monodispersed and showed sufficient purity. When quinate dehydrogenase purification was done with Acinetobacter calcoaceticus AC3, which is unable to synthesize PQQ, purified inactive apo-quinate dehydrogenase appeared to be a dimer and it was converted to the monomeric active holo-quinate dehydrogenase by the addition of PQQ.

Alcohol Oxidoreductases↗
PubMed2003

Quantitative assessment of the total myocardial uptake ratio of 123I-BMIPP by using the Ishii-MacIntyre method is useful for predicting cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy.

We evaluated the usefulness of the total myocardial uptake ratio (TMUR) of 15-(p-[123I]iodophenyl)-3(R,S)-methyl-pentadecanoic acid (123I-BMIPP) for predicting cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy. Six patients with mitochondrial encephalomyopathy, four with myotonic dystrophy, and 10 control subjects were studied. Quantitative assessment of 123I-BMIPP dynamic myocardial imaging was performed, and the TMUR of 123I-BMIPP was calculated according to the Ishii-MacIntyre method. Then, the TMUR was compared in the 10 patients and 10 healthy controls, and all patients were followed for 56.1+/-22.1 months to evaluate cardiac complications. TMUR in patients (2.69+/-0.64) was significantly (P =0.01) lower than that in controls (3.28+/-0.25). Three patients in whom the TMUR value was above 3.00 had no cardiac complications. On the other hand, all patients in whom TMUR was below 3.00 had some kind of cardiac complication during the follow-up period. Two patients showed progressive conduction abnormality and underwent pacemaker implantation, one patient had sick sinus syndrome and underwent pacemaker implantation, another patient showed non-sustained ventricular tachycardia and paroxysmal atrial fibrillation, and four of seven patients, including one with a pacemaker, showed an increased cardiothoracic ratio value over 50%. In conclusion, measurement of the TMUR by the Ishii-MacIntyre method is useful for evaluating the development of cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy.

Adult↗
PubMed2002

New developments in oxidative fermentation.

Oxidative fermentations have been well established for a long time, especially in vinegar and in L-sorbose production. Recently, information on the enzyme systems involved in these oxidative fermentations has accumulated and new developments are possible based on these findings. We have recently isolated several thermotolerant acetic acid bacteria, which also seem to be useful for new developments in oxidative fermentation. Two different types of membrane-bound enzymes, quinoproteins and flavoproteins, are involved in oxidative fermentation, and sometimes work with the same substrate but produce different oxidation products. Recently, there have been new developments in two different oxidative fermentations, D-gluconate and D-sorbitol oxidations. Flavoproteins, D-gluconate dehydrogenase, and D-sorbitol dehydrogenase were isolated almost 2 decades ago, while the enzyme involved in the same oxidation reaction for D-gluconate and D-sorbitol has been recently isolated and shown to be a quinoprotein. Thus, these flavoproteins and a quinoprotein have been re-assessed for the oxidation reaction. Flavoprotein D-gluconate dehydrogenase and D-sorbitol dehydrogenase were shown to produce 2-keto- D-gluconate and D-fructose, respectively, whereas the quinoprotein was shown to produce 5-keto- D-gluconate and L-sorbose from D-gluconate and D-sorbitol, respectively. In addition to the quinoproteins described above, a new quinoprotein for quinate oxidation has been recently isolated from Gluconobacter strains. The quinate dehydrogenase is also a membrane-bound quinoprotein that produces 3-dehydroquinate. This enzyme can be useful for the production of shikimate, which is a convenient salvage synthesis system for many antibiotics, herbicides, and aromatic amino acids synthesis. In order to reduce energy costs of oxidative fermentation in industry, several thermotolerant acetic acid bacteria that can grow up to 40 degrees C have been isolated. Of such isolated strains, some thermotolerant Acetobacter species were found to be useful for vinegar fermentation at a high temperature such 38-40 degrees C, where mesophilic strains showed no growth. They oxidized higher concentrations of ethanol up to 9% without any appreciable lag time, while alcohol oxidation with mesophilic strains was delayed or became almost impossible under such conditions. Several useful Gluconobacter species of thermotolerant acetic acid bacteria are also found, especially L-erythrulose-producing strains and cyclic alcohol-oxidizing strains. Gluconobacter frateurii CHM 43 is able to rapidly oxidize meso-erythritol at 37 degrees C leading to the accumulation of L-erythrulose, which may replace dihydroxyacetone in cosmetics. G. frateuriiCHM 9 is able to oxidize cyclic alcohols to their corresponding cyclic ketones or aliphatic ketones, which are known to be useful for preparing many different physiologically active compounds such as oxidized steroids or oxidized bicyclic ketones. The enzymes involved in these meso-erythritol and cyclic alcohol oxidations have been purified and shown to be a similar type of membrane-bound quinoproteins, consisting of a high molecular weight single peptide. This is completely different from another quinoprotein, alcohol dehydrogenase of acetic acid bacteria, which consists of three subunits including hemoproteins.

Acetic Acid↗