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Biomedical subjects

Hiroyuki Yamada

Publications and source records attributed to Hiroyuki Yamada.

At least 19 recordsLinked to original sources
PubMed2007

Efficacy prediction of cevimeline in patients with Sjögren's syndrome.

The objective of this study was to examine the clinical and immunological factors influencing the efficacy of cevimeline hydrochloride hydrate (cevimeline) for the treatment of xerostomia in patients with Sjögren's syndrome (SS). Thirty primary SS patients who were medicated with cevimeline were enrolled in this study. Whole stimulated sialometry (WSS) was compared between pre- and posttreatment points (4 weeks after oral cevimeline administration) and the increment rate of WSS was calculated. Multiple regression was employed to examine the relative contributions of the clinical and immunological factors, including age, pretreatment WSS, duration of disease, sialography, minor salivary gland biopsy, anti-Ro/SS-A antibodies, anti-La/SS-B antibodies, and antibodies to muscarinic type 3 receptors to the posttreatment WSS. Patients with normal sialography findings, negative minor salivary gland biopsy, and absence of anti-La/SS-B antibodies had significantly higher increment rates of WSS compared with those with positive findings (p=0.042, 0.002, and 0.018, respectively). Results of the multiple regression analysis showed that sialography (coefficient=-0.867, p=0.004) and minor salivary gland biopsy (coefficient=-0.869, p=0.003) had significant associations with the posttreatment WSS. Our preliminary results demonstrated the relationship between the effect of cevimeline on saliva secretion and the degree of salivary gland destruction evaluated by sialography and histopathological findings in the labial minor salivary glands. These diagnostic approaches could provide useful prognostic information on the efficacy of cevimeline in SS patients.

Adult↗
PubMed2006

Epithelial-myoepithelial carcinoma of the submandibular gland with a high uptake of 18F-FDG: a case report and image diagnosis.

Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade malignant salivary gland neoplasm typically found in the parotid gland. This report describes a case of EMC that arose from the submandibular gland, and gives special emphasis to the preoperative diagnostic value of positron emission tomography (PET) in combination with computed tomography (CT) and magnetic resonance imaging (MRI). Although a preoperative diagnostically specific image of EMC could not be established, the malignant nature of this tumor was detected by these combined examinations.

Aged↗
PubMed2006

Calculation of the penetration depth of X-rays in intact pharmaceutical film-coated tablets by microdiffractometry.

PURPOSE: (i) Develop a method to calculate the penetration depth of X-rays in intact film-coated tablets, and validate it using model bilayer tablets. (ii) Characterize the physical form of drug in intact pharmaceutical film-coated tablets by XRD. MATERIALS AND METHODS: An equation for the calculation of the penetration depth of X-rays, as a function of the incident angle, was derived. Model bilayer tablets were prepared to validate the calculation method. The upper layer of the tablets consisted only of microcrystalline cellulose, while the lower layer was a mixture of cerium oxide (10% w/w), blue dye (5% w/w) and microcrystalline cellulose. The total tablet thickness was 3,500 microm, with the upper layer thickness ranging from 200 to 700 microm. The diffracted intensity of a cerium oxide peak in the lower layer was determined using a microdiffractometer system (CuKalpha radiation) with a two-dimensional area detector. The calculated penetration depth of X-rays was compared with that determined by XRD. After validation of the XRD method, commercial ibuprofen tablets were characterized. RESULTS: The penetration depth calculated by the method developed in this study was, in general, in good agreement with that determined experimentally by XRD. In commercial ibuprofen tablets, the coating material exhibited peaks due to TiO2 (25.4 degrees 2 theta) and Fe2O3 (33.3 degrees). However, these did not interfere with the characteristic peak of ibuprofen (22.2 degrees). CONCLUSION: We developed a method for calculation of penetration depth of X-rays in film-coated tablets and validated it using the model bilayer tablets. This method enables the characterization of the active pharmaceutical ingredient in different regions (at different depths) of the film-coated tablet. Since the technique is nondestructive, the same tablet can be repeatedly analyzed during stability studies.

Absorption↗
PubMed2006

Effect of electrical stimulation of the internal capsule on nociceptive neurons responding to orofacial stimuli in the medullary dorsal horn of the rat.

Internal capsule (IC) stimulation has been used clinically to alleviate central pain. However, the neuronal mechanisms underlying pain relief by IC stimulation are poorly understood. In order to elucidate the analgesic mechanism, the effect of IC conditioning stimulation on nociceptive neurons in the rat medullary dorsal horn was investigated in the present study. Rats were anaesthetized with N(2)O-O(2) (2:1) and 0.5% halothane and were immobilized with pancuronium bromide. Two kinds of nociceptive neurons, wide dynamic range (WDR) and nociceptive specific (NS) neurons, responding to noxious stimulations of the face and oral structures were recorded in the trigeminal caudal nucleus and the medial reticular subnuclei. A test stimulus with a single rectangular pulse (2ms in duration, 5-70V) was applied to the centre of the receptive field. Responses in 55.9% of the WDR neurons and in 60% of the NS neurons were inhibited by conditioning stimuli to the ipsilateral IC with trains of 33 pulses (100-300microA) at 330Hz. The percents of peak inhibitory effects on WDR neurons and NS neurons were 78.1+/-25.0% (n=19) and 89.0+/-13.6% (n=3), respectively. The inhibitory effect continued for conditioning-test intervals of up to 500ms. Effective sites for conditioning stimulation were concentrated in the lateral side of the IC. These findings suggest that modulation of nociceptive transmission by IC stimulation occurs at second-order neurons via a presynaptic phenomenon by corticofugal fibers in the IC.

Animals↗
PubMed2006

Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia.

We investigated whether the mobilization of endothelial progenitor cells (EPCs) by exogenous erythropoietin (Epo) promotes the repair of injured endothelium. Recombinant human Epo was injected (1000 IU/kg for the initial 3 days) after wire injury of the femoral artery of mice. Neointimal formation was inhibited by Epo to 48% of the control (P<0.05) in an NO-dependent manner. Epo induced a 1.4-fold increase in reendothelialized area of day 14 denuded vessels, 55% of which was derived from bone marrow (BM) cells. Epo increased the circulating Sca-1(+)/Flk-1(+) EPCs (2.0-fold, P<0.05) with endothelial properties NO dependently. BM replacement by GFP- or beta-galactosidase-overexpressing cells showed that Epo stimulated both differentiation of BM-derived EPCs and proliferation of resident ECs. BM-derived ECs increased 2.2- to 2.7-fold (P<0.05) in the Epo-induced neoendothelium, where the expression of Epo receptor was upregulated. Epo induced Akt/eNOS phosphorylation and NO synthesis on EPCs and exerted an antiapoptotic action on wire-injured arteries. In conclusion, Epo treatment inhibits the neointimal hyperplasia after arterial injury in an NO-dependent manner by acting on the injured vessels and mobilizing EPCs to the neo-endothelium.

Animals↗
PubMed2006

Induction of myasthenia by immunization against muscle-specific kinase.

Muscle-specific kinase (MuSK) is critical for the synaptic clustering of nicotinic acetylcholine receptors (AChRs) and plays multiple roles in the organization and maintenance of neuromuscular junctions (NMJs). MuSK is activated by agrin, which is released from motoneurons, and induces AChR clustering at the postsynaptic membrane. Although autoantibodies against the ectodomain of MuSK have been found in a proportion of patients with generalized myasthenia gravis (MG), it is unclear whether MuSK autoantibodies are the causative agent of generalized MG. In the present study, rabbits immunized with MuSK ectodomain protein manifested MG-like muscle weakness with a reduction of AChR clustering at the NMJs. The autoantibodies activated MuSK and blocked AChR clustering induced by agrin or by mediators that do not activate MuSK. Thus MuSK autoantibodies rigorously inhibit AChR clustering mediated by multiple pathways, an outcome that broadens our general comprehension of the pathogenesis of MG.

Agrin↗
PubMed2006

Evaluation of allodynia and pain associated with postherpetic neuralgia using current perception threshold testing.

OBJECTIVES: Postherpetic neuralgia has various clinical features, and the implicated pathophysiologic mechanisms are controversial. This study was carried out to clarify the roles of peripheral sensory nerves in the production of allodynia and ongoing pain. Current perception threshold (CPT) testing was used to evaluate the sensory function. METHODS: The intensities of ongoing pain and dynamic allodynia were assessed using a numeric rating scale (0-10). Assessment of sensory nerve function was performed by a series of 2,000-, 250-, and 5-Hz stimuli using CPT testing. These measurements were made in ipsilateral and contralateral area. RESULTS: CPTs at all frequencies in the ipsilateral area were significantly higher than those in the contralateral area. There were significant and inverse correlations between the intensity of allodynia and CPTs at all frequencies. No correlation was found between the intensity of ongoing pain and CPTs at any frequency. There was no correlation between the intensity of ongoing pain and the intensity of dynamic allodynia. CONCLUSIONS: The intensity of dynamic allodynia in postherpetic neuralgia correlates with the preserved functions of Abeta, Adelta, and C fibers. In contrast, the intensity of ongoing pain does not correlate with either the preserved function of C fibers or the intensity of dynamic allodynia. Therefore, it is suggested that postherpetic neuralgia might be a pain syndrome including both peripheral and central mechanisms.

Aged↗
PubMed2006

Nude rat (F344/N-rnu) tuberculosis.

As many mononuclear cells from Mycobacterium tuberculosis-infected lung tissues are not available for fluorescence-activated cell sorter (FACS) analysis and the tuberculin test is not feasible in a mouse tuberculosis model, we attempted to develop a rat tuberculosis model. We have previously reported that rat tuberculosis is associated with granulomas that lack central necrosis. In order to develop a better animal model of tuberculosis in immunocompromised humans (tuberculosis associated with HIV infection or tuberculosis of the elderly), we infected F344/N-rnu nude rats with M. tuberculosis via the airborne route. The animals developed pulmonary granulomas with central necrosis encapsulated by dense collagen fibres, closely resembling those of human tuberculosis. The nude rats died of disseminated tuberculosis by the 85th day after aerosol infection, while F344 wild-type rats did not. Interestingly, T-cells that were reactive with anti-CD4 antibody and anti-CD8 antibody, indicating the presence of remnant thymus, were observed in the infected lung tissues of the nude rats. Therefore, T-cell precursors may be present in nude rats. The nude rat tuberculosis model mimics tuberculosis in immunocompromised humans and may provide a suitable model for immunological studies in vivo.

Animals↗
PubMed2006

Relation of obesity to acute myocardial infarction in Japanese patients.

BACKGROUND: It remains uncertain whether obesity is an independent risk factor for coronary heart disease in young adults, as well as adults, in Japan. METHODS AND RESULTS: In the present study, 1,260 cases of acute myocardial infarction (AMI) and 3,775 community controls were recruited from the AMI-Kyoto Multi-Center Risk Study and Kyoto Citizen's Health and Nutrition Study, respectively. Obesity and other risk factors were retrospectively examined between cases and controls in each subgroup of young males (20-40 years), middle-aged males or females (40-60 years), older males or females (60-80 years), and very old males or females (80-100 years). In young, middle-aged, and older males, as well as in older females, cases had a higher body mass index (BMI) than controls. In young males, as well as in middle-aged and older females, cases had a higher prevalence of smoking than controls. Except for very old males, the prevalences of hypercholesterolemia, hypertension, and diabetes mellitus were higher in each subgroup of cases than in controls. Multivariate logistic regression analysis revealed that obesity (BMI >or=25) was an independent risk for AMI in young and middle-aged males, but not in females, whereas smoking was an independent risk for AMI in middle-aged and older females as well as in older males. CONCLUSIONS: Obesity is significantly associated with AMI, independent of the classic coronary risk factors, in young and middle-aged males. These findings support the current emphasis on controlling obesity to prevent coronary events in young Japanese male adults.

Adult↗
PubMed2006

[Current status and evaluation of laparoscopic surgery for gastric cancer].

Laparoscopic surgery for gastric cancer in Japan has been established as a treatment for early gastric cancer after technical improvements, development of instruments, and efforts of surgeons. The technigue was extended to some advanced gastric cancers and now plays an important role in the gastric cancer treatment strategy with open surgery and endoscopic mucosal resection. Laparoscopic surgery for early gastric cancer has been evaluated as less invasive, offering radical cure, and safe in several clinical trials and case-control studies. However, the accumulation of more cases and additional basic research are necessary before adapting laparoscopic surgery for advanced gastric cancer. A large-scale, randomized, controlled study will be carried out in early gastric cancer, and, as a result, scientific and objective evaluation of laparoscopic surgery for gastric cancer will be possible in the near future.

Gastrectomy↗
PubMed2005

Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice.

BACKGROUND: Increased production of reactive oxygen species (ROSs) by angiotensin II (Ang II) is involved in the initiation and progression of cardiovascular diseases. NADPH oxidase is a major source of superoxide generated in vascular tissues. Although Nox1 has been identified in vascular smooth muscle cells as a new homolog of gp91phox (Nox2), a catalytic subunit of NADPH oxidase, the pathophysiological function of Nox1-derived ROSs has not been fully elucidated. To clarify the role of Nox1 in Ang II-mediated hypertension, we generated Nox1-deficient (-/Y) mice. METHODS AND RESULTS: No difference in the baseline blood pressure was observed between Nox1(+/Y) and Nox1(-/Y). Infusion of Ang II induced a significant increase in mean blood pressure, accompanied by augmented expression of Nox1 mRNA and superoxide production in the aorta of Nox1(+/Y), whereas the elevation in blood pressure and production of superoxide were significantly blunted in Nox1(-/Y). Conversely, the infusion of pressor as well as subpressor doses of Ang II did elicit marked hypertrophy in the thoracic aorta of Nox1(-/Y) similar to Nox1(+/Y). Administration of a nitric oxide synthase inhibitor (L-NAME) to Nox1(+/Y) did not affect the Ang II-mediated increase in blood pressure, but it abolished the suppressed pressor response to Ang II in Nox1(-/Y). Finally, endothelium-dependent relaxation and the level of cGMP in the isolated aorta were preserved in Nox1(-/Y) infused with Ang II. CONCLUSIONS: A pivotal role for ROSs derived from Nox1/NADPH oxidase was suggested in the pressor response to Ang II by reducing the bioavailability of nitric oxide.

Angiotensin II↗
PubMed2005

A pilot approach for quantitative assessment of liver fibrosis using ultrasound: preliminary results in 79 cases.

BACKGROUND/AIMS: Ultrasound is noninvasive and useful to evaluate liver disease despite its operator dependency. This pilot study was conducted to quantitatively assess liver fibrosis using ultrasound. METHODS: Fibrosis extraction ratios (FER) (fiber volume/total volume) of ultrasound and histological images of 8 autopsy specimens were compared. We also compared FER of ultrasound images from clinical patients (n=79) with histological fibrosis stages. RESULTS: In the autopsy study, FER correlation coefficient between histological images and ultrasound images was 0.992. Regarding clinical patients, there was sufficient evidence to indicate differences in the distributions of FER for each fibrosis stage (Kruskal-Wallis test P<0.0001). With FER cut-off to distinguish > or =F2 from F0 and F1 defined as mean plus standard deviation of F0 and F1, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were 62, 75, 78, 57%, and 2.47, respectively. Regarding HCV cohort (n=44), they were 55, 87, 89, 50%, and 4.14, respectively. Areas under receiver operating characteristic curves were 0.78, 0.79, 0.83 and 0.83 for > or =F1, > or =F2, > or =F3 and =F4, respectively. Regarding HCV cohort, they were 0.74, 0.71, 0.79 for > or =F2, > or =3 and =4, respectively. CONCLUSIONS: The FER method has great potential for diagnosing liver fibrosis using ultrasound.

Adult↗
PubMed2005

Liver cirrhosis induced by long-term administration of a daily low dose of amiodarone: a case report.

The anti-arrhythmic agent amiodarone (AD) is associated with numerous adverse effects, but serious liver disease is rare. The improved safety of administration of daily low doses of AD has already been established and this regimen is used for long-term medication. Nevertheless, asymptomatic continuous liver injury by AD may increase the risk of step-wise progression of non-alcoholic fatty liver disease. We present an autopsy case of AD-induced liver cirrhosis in a patient who had been treated with a low dose of AD (200 mg/d) daily for 84 mo. The patient was a 85-year-old male with a history of ischemic heart disease. Seven years after initiation of treatment with AD, he was admitted with cardiac congestion. The total dose of AD was 528 g. Mild elevation of serum aminotransferase and hepatomegaly were present. Liver biopsy specimens revealed cirrhosis, and under electron microscopy numerous lysosomes with electron-dense, whorled, lamellar inclusions characteristic of a secondary phospholipidosis were observed. Initially, withdrawal of AD led to a slight improvement of serum aminotransferase levels, but unfortunately his general condition deteriorated and he died from complications of pneumonia and renal failure. Long-term administration of daily low doses of AD carries the risk of progression to irreversible liver injury. Therefore, periodic examination of liver function and/or liver biopsy is required for the management of patients receiving long-term treatment with AD.

Aged↗
PubMed2005

Temperature-mediated heteroduplex analysis for the detection of drug-resistant gene mutations in clinical isolates of Mycobacterium tuberculosis by denaturing HPLC, SURVEYOR nuclease.

Denaturing high-performance liquid chromatography (DHPLC) is a relatively new technique, which utilizes heteroduplex formation between wild-type and mutated DNA strands to identify point mutations. Heteroduplex molecules are separated from homoduplex molecules by ion-pair, reverse-phase liquid chromatography on a special column matrix with partial heat denaturation of the DNA strands. In order to investigate the application of this method for point mutation detection in drug-resistant genes of Mycobacterium tuberculosis, katG, rpoB, embB, gyrA, pncA and rpsL genes, which are responsible for isoniazid, rifampicin, ethambutol, fluoroquinolone, pyrazinamide and streptomycin resistance, respectively, were detected by temperature-mediated DHPLC in 10 multidrug-resistant and 10 drug-susceptible clinical isolates. The DHPLC data were compared with those from a conventional MIC test. The results show that DHPLC is cost-effective with high capacity and accuracy, and is potentially useful for genotypic screening for mutations associated with anti-tuberculosis drug resistance.

Antitubercular Agents↗
PubMed2005

Sexual dimorphism of cusp dimensions in human maxillary molars.

Cusp dimensions of human maxillary molars were compared between males and females to determine whether the later-developed, distal cusps displayed greater sexual dimorphism than the earlier-developed, mesial cusps, and whether the later-forming second molar displayed greater sexual dimorphism than the first molar. First and second permanent molar crowns (M1 and M2) were measured indirectly, using dental casts obtained from 117 Japanese (65 males and 52 females). Measurements included maximum mesiodistal and buccolingual crown diameters and the diameters of the four main cusps: the paracone, protocone, metacone, and hypocone. Mean values of crown dimensions were larger in males than in females for both M1 and M2, but the sexual difference in protocone diameter of M1 was not significant. The protocone in M1 showed the least amount of sexual dimorphism, followed by the metacone, hypocone, and paracone, while in M2, the percentage sexual dimorphism corresponded to the order of cusp formation: paracone, protocone, metacone, and hypocone. With the exception of the paracone diameter, M2 showed greater sexual dimorphism than M1. Sexual dimorphism was not always greater in the later-developed, distal cusps of M1 or M2, but the protocone, the most important cusp in terms of occlusal function, displayed the least dimorphism in M1.

Adult↗