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Biomedical subjects

K Matsunaga

Publications and source records attributed to K Matsunaga.

At least 19 recordsLinked to original sources
PubMed2006

Improvement of pulmonary function and dyspnea by tiotropium in COPD patients using a transdermal beta(2)-agonist.

BACKGROUND: A combination of bronchodilators may be effective in the treatment of chronic obstructive pulmonary disease (COPD). We examined the effect of adding a long-acting anti-cholinergic agent (tiotropium) to a transdermal-type beta(2)-agonist (tulobuterol) on dyspnea as well as pulmonary function. METHODS: In a multicentre, randomized, parallel design study, 60 COPD patients treated with the transdermal beta(2)-agonist tulobuterol were divided into a tiotropium added group (Tulo+Tio group, n=40) or transdermal beta(2)-agonist tulobuterol alone group (Tulo group, n=20), and then treated for 4 weeks after a 2 week run-in period. Pulmonary function and a dyspnea (Medical Research Council (MRC)) scale were assessed before and after the treatment. Daily peak expiratory flow (PEF) monitoring was also performed. RESULTS: After 4 weeks, the Tulo+Tio group showed a significant increase in pulmonary function compared with the Tulo group; DeltaFVC (0.31+/-0.06 L vs. 0.06+/-0.05 L, p< 0.01), DeltaFEV(1) (0.15+/-0.03 L vs. -0.02+/-0.02 L, p<0.0001), and DeltaPEF (41.0+/-5.1 L/min vs. 0.5+/-3.5 L/min, p<0.0001). The MRC dyspnea scale was also significantly improved in Tulo+Tio, but not in Tulo group. CONCLUSION: These results suggest that tiotropium caused a significant improvement in both pulmonary function and dyspnea in COPD patients already treated with the transdermal beta(2)-agonist tulobuterol.

Administration, Cutaneous↗
PubMed2006

Grain boundary strengthening in alumina by rare earth impurities.

Impurity doping often alters or improves the properties of materials. In alumina, grain boundaries play a key role in deformation mechanisms, particularly in the phenomenon of grain boundary sliding during creep at high temperatures. We elucidated the atomic-scale structure in alumina grain boundaries and its relationship to the suppression of creep upon doping with yttrium by using atomic resolution microscopy and high-precision calculations. We find that the yttrium segregates to very localized regions along the grain boundary and alters the local bonding environment, thereby strengthening the boundary against mechanical creep.

Journal Article↗
PubMed2006

Inhibition of reactive nitrogen species production in COPD airways: comparison of inhaled corticosteroid and oral theophylline.

BACKGROUND: Reactive nitrogen species (RNS) are thought to be one of the important factors in the pathogenesis of chronic obstructive pulmonary disease (COPD). A study was undertaken to examine the effects of theophylline and fluticasone propionate (FP) on RNS production in subjects with COPD. METHODS: Sixteen COPD subjects participated in the study. Theophylline (400 mg/day orally) or FP (400 mug/day inhalation) were administered for 4 weeks in a randomised crossover manner with a washout period of 4 weeks. Induced sputum was collected at the beginning and end of each treatment period. 3-nitrotyrosine (3-NT), which is a footprint of RNS, was quantified by high performance liquid chromatography with an electrochemical detection method as well as by immunohistochemical staining. RESULTS: Theophylline significantly reduced the level of 3-NT in the sputum supernatant as well as the number of 3-NT positive cells (both p<0.01). FP also reduced 3-NT formation, but the effect was smaller than that of theophylline. Theophylline also significantly reduced the neutrophil cell counts in the sputum (p<0.01), while FP treatment had no effect on the number of inflammatory cells in the sputum, except eosinophils. CONCLUSIONS: Theophylline reduces nitrative stress and neutrophil infiltration in COPD airways to a larger extent than inhaled corticosteroid.

Administration, Inhalation↗
PubMed2005

Patency assessment of the internal jugular vein after neck dissection.

Twenty-seven patients with oral malignant tumours, who underwent neck dissection with preservation of the internal jugular vein (IJV), were studied retrospectively to evaluate patency of the IJV. Twenty-three patients underwent ablative surgery of the primary lesion with neck dissection and 4 underwent neck dissection alone. Three patients received simple closure and skin grafting of the primary lesion, and 20 received reconstruction surgery (4 platysma flaps, 3 radial forearm flaps, 3 lateral upper arm flaps, 2 pectoralis major myocutaneous flaps and 8 rectus abdominis myocutaneous flaps). The maximum and minimum diameters of the IJV as measured on computed tomographic (CT) scans were used to assess patency. The cross-sectional area of the IJV and the ratio of its long axis to short axis (L/S ratio) were calculated. The relation between the change in IJV status and the type of flap used for reconstruction was also examined. Occlusion of the IJV was present in 3.7% of the patients, and 'narrowing' was present in 63.6%. The size of the flap significantly correlated with 'narrowing' of the IJV, suggesting that 'narrowing' was caused mainly by compression due to the flap.

Carcinoma, Squamous Cell↗
PubMed2005

Dopaminergic drugs restore facilitatory premotor-motor interactions in Parkinson disease.

OBJECTIVE: To explore the impact of dopaminergic therapy on facilitatory premotor-motor interactions in patients with Parkinson disease (PD). METHODS: Ten patients with PD and 10 age-matched healthy volunteers received repetitive transcranial magnetic stimulation (rTMS) over the left dorsal premotor cortex (5 Hz, 1,500 stimuli, 90% of active motor threshold). Patients were studied while "on" and "off" medication. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseus muscle before and after rTMS to quantify changes in motor cortical excitability. The after-effects of rTMS on motor function were assessed using the Unified Parkinson's Disease Rating Scale and the kinematics of ballistic wrist flexions. RESULTS: MEPs evoked from the ipsilateral motor cortex were increased after premotor rTMS in relaxed normal subjects, consistent with an increase in motor cortex excitability. In patients with PD, the effect of premotor rTMS was modified by medication. When patients were in a practically defined "off" state, premotor rTMS had no effect on MEPs, whereas when they were in the "on" state, premotor rTMS facilitated MEPs. Premotor rTMS had no effect on clinical parkinsonian symptoms or motor performance of ballistic wrist movements, regardless of whether patients were in the "on" or "off" state. CONCLUSIONS: In Parkinson disease, the ability of premotor-motor connections to increase motor cortical excitability is defective but restored to normal by dopaminergic medication. Dopamine deficiency in the basal ganglia may affect the way that frontal motor areas interact with each other.

Adult↗
PubMed2003

Novel mutations in GJB2 encoding connexin-26 in Japanese patients with keratitis-ichthyosis-deafness syndrome.

BACKGROUND: Germline missense mutations in the GJB2 gene that encodes connexin-26 (Cx26) have recently been found to be the cause of the keratitis-ichthyosis-deafness (KID) syndrome. OBJECTIVES: To define the GJB2 mutations in three Japanese patients with KID syndrome. METHODS: Genomic DNA was extracted from peripheral blood and used to amplify the GJB2 gene. Direct sequencing and endonuclease digestion were used for mutation analysis and DNA-based diagnosis. RESULTS: We identified two heterozygous mis-sense mutations (D50Y, D50N) in the GJB2 gene in three Japanese patients with KID syndrome. All mutations were located on the first extracellular domain of Cx26. CONCLUSIONS: These data expand the GJB2 mutation database and show that a dominant mutation of Cx26 can cause KID syndrome in Japanese patients.

Adult↗
PubMed2003

Interindividual variation of serum haloperidol concentrations in Japanese patients--clinical considerations on steady-state serum level-dose ratios.

OBJECTIVE: Marked interpatient variability in haloperidol (HAL) level-dose (L/D) ratios makes it difficult to use the administered dose for predicting serum concentrations. OBJECTIVE: To investigate the effect of dose, age, total body weight and co-medication on steady-state HAL L/D ratios. METHOD: Retrospective analysis of dose and HAL blood level data from 168 patients. RESULTS: The HAL L/D ratio decreased curvilinearly with increasing daily dose of HAL. The patients treated with concomitant antiparkinsonian drugs showed a mean HAL L/D ratio that was 24.9% higher than those without antiparkinsonian drugs. The patients treated with concomitant antiepileptic drugs showed a mean HAL L/D ratio that was 27.2% lower than those without antiepileptic drugs. The mean HAL L/D ratio of patients treated with concomitant CYP2D6 substrates was not significantly different from those without CYP2D6 substrates. CONCLUSION: There is a wide interindividual variability in blood levels of HAL in patients given the same dose. Routine monitoring of HAL serum level is useful, especially in patients who require associated antiepileptic and/or antiparkinsonian medication.

Adult↗
PubMed2003

Influence of hemodialysis on echocardiographic Doppler indices of the left ventricle: changes in parameters of systolic and diastolic function and Tei index.

AIMS: Numbers of previous studies have evaluated the influence of dialysis-induced altered loading condition on Doppler-echocardiographic indices of left ventricle in patients with chronic renal failure. It has been suggested that most of Doppler-derived indices are preload-dependent. On the other hand, there are no studies that have evaluated the influence of hemodialysis on Tei index; a new Doppler-derived index obtained by isovolumetric contraction time plus isovolumetric relaxation time divided by ejection time. The aim of this study is to evaluate whether Tei index is also influenced by dialysis-induced altered loading condition as well as other Doppler-derived indices, and to assess the possibility that Tei index is also preload-dependent. PATIENTS AND METHODS: Thirty-two patients with chronic renal failure (21 men and 11 women, aged 48-93 years) on maintenance hemodialysis were evaluated for Doppler-derived indices before and after hemodialysis. We studied parameters of diastolic function (peak velocities of mitral inflow in early diastole (E) and late diastole from atrial filling (A), ratio of A to E (A/E), deceleration time (DT), and isovolumetric relaxation time (IRT)), parameters of systolic function (ejection time (ET), pre-ejection period (PEP), ratio of PEP to ET (PEP/ET), and isovolumetric contraction time (ICT)) and Tei index. RESULTS: Hemodialysis resulted in significant decreases in E, increase in A/E, prolongation of IRT, no change in A and DT; significant prolongation of ICT and PEP, shortening of ET, and increase in PEP/ET and a significant increase in Tei index (0.42 +/- 0.16 vs 0.51 +/- 0.16, p < 0.0001). When patients were subdivided into 2 groups based on weight loss after hemodialysis (> or = 1.5 kg and < 1.5 kg), only the group that lost > or = 1.5 kg had significant change in Tei index before and after hemodialysis (0.40 +/- 0.15 vs 0.52 +/- 0.17, p = 0.0002). CONCLUSION: This study demonstrates that not only most of Doppler-derived indices but also Tei index is affected by dialysis-induced altered loading condition and suggests that Tei index is possibly preload-dependent.

Aged↗
PubMed2003

The pilot trial of the prevention of the increase in electrical taste thresholds by zinc containing fluid infusion during chemotherapy to treat primary lung cancer.

It is well known that there are various adverse effects during chemotherapy for cancer treatment. A taste disorder is also seen in 35-70% of patients. It has been reported that a zinc deficiency is associated with the development of these alterations in taste sensation. The purpose of this pilot study was to determine whether the zinc including infusion had the effect on taste disorder in patients with lung cancer. Taste disorder was evaluated as the increase in electrical taste thresholds using an electrogustometer. The plasma zinc concentration was also measured. Although there was no significant correlation, the increase in taste thresholds was detected in many patients who had a low zinc concentration even before receiving chemotherapy. Moreover, after 2 weeks of chemotherapy, almost all patients who did not have a zinc containing infusion showed development of taste disorder (5/5, 100% at chorda tympani area; 4/5, 80% at glossopharyngeal area), whereas no development of taste disorder was observed in those patients receiving a zinc containing infusion. These results suggest the possibility that the administration of zinc during chemotherapy could be a useful supportive therapy for preventing taste disorder and to help maintain a better quality of life.

Aged↗
PubMed2002

Potent apoptotic effects of saponins from Liliaceae plants in L1210 cells.

We isolated eight saponins, a hexacyclic lanosterol tetraglycoside (1), a 27-norlanosterol tetraglycoside (2) and six spirostanol oligoglycosides (3-8), from the plants of the family Liliaceae. In murine leukaemic L1210 cells, saponins 5 and 7 at a concentration of 1 microM showed potent cytotoxic activity and the activities were in the following decreasing order: 5, 7, 1, 3, 2, 8, 4, 6. At a concentration of 10 microM, not only 5 and 7 but also 3 and 8 markedly caused cell death. The flow cytometric analysis indicated that 7 and 8 caused a concentration- and time-dependent apoptosis of L1210 cells (EC50 value = approximately 5 microM). The morphological observation using a light microscope revealed that both 7 and 8 induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. Moreover, in agarose gel electrophoretic analysis, a typical apoptotic DNA ladder pattern was observed after treatment with both 7 and 8. These results suggest that 7 and 8 caused the death of L1210 cells through the apoptotic process. These compounds may become powerful pharmacological tools for studying the molecular mechanism of apoptosis.

Animals↗
PubMed2001

Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine.

Although nicotine is thought to be one of the major immunomodulatory components of cigarette smoking, how nicotine alters the host defense of the lung and, in particular, immune responses of alveolar macrophages, which are critical effector cells in the lung defense to infection, is poorly understood. Nicotinic acetylcholine receptors (nAChRs) are the receptor for nicotine and may be involved in the modulation of macrophage function by nicotine. In this study, therefore, nicotine-induced suppression of antimicrobial activity and cytokine responses of alveolar macrophages mediated by nAChRs to Legionella pneumophila, a causative agent for pneumonia, were examined. The murine MH-S alveolar macrophage cell line cells expressed the messages for alpha4 and beta2 subunits of nAChRs, but not alpha7 subunits, determined by RT-PCR. The nicotine treatment of MH-S alveolar macrophages after infection with L. pneumophila significantly enhanced the replication of bacteria in the macrophages and selectively down-regulated the production of IL-6, IL-12, and TNF-alpha, but not IL-10, induced by infection. These effects were completely blocked by a nonselective antagonist, d-tubocurarine, for nAChRs, but not by a selective antagonist, alpha-bungarotoxin, for alpha7-nAChRs. Furthermore, the stimulation of nAChRs with another agonist, 1,1-dimethyl-4-phenylpiperazinium iodide, showed the same effects, which were blocked by the antagonist d-tubocurarine, on the bacterial replication and cytokine regulation with that of nicotine. Thus, the results revealed that nAChRs, the major exogenous ligands of which are nicotine, are involved in the regulation of macrophage immune function by nicotine and may contribute to the cigarette-induced risk factors for respiratory infections in smokers.

Adjuvants, Immunologic↗
PubMed2001

Decreased susceptibility to pentylenetetrazol-induced seizures after low-frequency transcranial magnetic stimulation in rats.

We studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure susceptibility in rats. rTMS of 1000 pulses at 0.5 Hz led to a prolonged latency for seizure development after an intraperitoneal injection of pentylenetetrazol. The rTMS effectively prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. These findings indicate that low-frequency rTMS affects the neural excitability, in the direction of anticonvulsive, and therefore, suggest the possibility of therapeutic use of rTMS in epilepsy.

Animals↗
PubMed2001

Immunoreactivity of VR1 on epidermal keratinocyte of human skin.

We demonstrated the immunoreactivity of the receptor proteins, VR1, ion channels associated with pain sensation, on the epidermis of the human skin. Immunohistochemistry using antiserum against VR1 derived peptide showed immunoreactivity on the keratinocytes cell membrane of the human epidermis and cultured keratinocytes. The blocking peptide of the antiserum reduced the immunoreactivity on the epidermis. RT-PCR assay of cultured human keratinocyte also showed expression of VR1 mRNA. These results suggest the existence of VR1-like protein in epidermal keratinocytes of human skin.

Adult↗
PubMed2001

Sequential analysis of morphological and biological properties of beta-catenin-accumulated crypts, provable premalignant lesions independent of aberrant crypt foci in rat colon carcinogenesis.

Our previous study (Cancer Res., 60: 3323-3327, 2000) showed that frequent beta-catenin gene mutations are present in beta-catenin-accumulated crypts, which occur early in rodent colonic carcinogenesis, with a lack of the appearance of aberrant crypt foci (ACF). To clarify the nature of such lesions, we performed a sequential analysis of the morphological and biological properties of beta-catenin-accumulated crypts. Azoxymethane was administered s.c. to male F344 rats (15 mg/kg body weight) once a week for 3 weeks, and the animals were sacrificed at 5, 10, and 20 weeks after the carcinogen treatment. Both the number of crypts/lesion and the diameter of beta-catenin-accumulated crypts were significantly increased with time courses of 5, 10, and 20 weeks from carcinogen exposure (P < 0.01). Likewise, the histological abnormality in those crypts, assessed by semiquantitative analyses, was also increased with time (P < 0.01). Conversely, ACF did not show any increase in histological abnormality during the time course and maintained a monotonous histology throughout the experiment. The histological abnormality score for beta-catenin-accumulated crypts was significantly higher than for ACF at every time point (P < 0.001). The number of AgNOR/nucleus in beta-catenin-accumulated crypts was significantly higher than in ACF (P < 0.001). Beta-catenin-accumulated crypts were accompanied frequently by Paneth cells and had decreased hexosaminidase activity. Such data, together with the results in our previous report, strongly suggest that beta-catenin-accumulated crypts, which are independent of ACF, are truly premalignant lesions for colon cancer.

Animals↗