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Biomedical subjects

T Kuriyama

Publications and source records attributed to T Kuriyama.

At least 37 records · Page 2Linked to original sources

Clinical characteristics of acute pulmonary thromboembolism in Japan: results of a multicenter registry in the Japanese Society of Pulmonary Embolism Research.

BACKGROUND: Although the incidence of acute pulmonary thromboembolism (APTE) has been increasing in Japan, patient characteristics, management strategies, and outcome have not yet been assessed in large series. HYPOTHESIS: The present study was designed to investigate the current status of APTE in Japan. METHODS: Of a total of 533 registry patients with pulmonary thromboembolism, 309 with APTE were analyzed with respect to clinical symptoms and signs, predisposing factors, diagnostic procedures, estimation of deep venous thrombosis, treatment, and clinical course. RESULTS: Main risk factors were recent major surgery, cancer, prolonged immobilization, and obesity; only a few patients had coagulopathy and 36% were in cardiogenic shock at presentation. The majority of registry patients underwent lung scans or pulmonary angiography; 30% were diagnosed only by lung scanning. Venous ultrasonography was used in only 34 patients, while 188 patients underwent at least one diagnostic procedure for deep venous thrombosis. Thrombolysis was more frequently performed in patients with cardiogenic shock, and only a few patients received thromboembolectomy. In-hospital mortality rate was 14%. In patients with cardiogenic shock, the mortality rate was reduced by thrombolysis. The predictors of in-hospital mortality were male gender, cardiogenic shock, cancer, and prolonged immobilization. CONCLUSIONS: The patients in this registry had almost the same findings as those in Western patients, except for some points that had the possibility of demonstrating a difference between Westerners and Japanese in the development of APTE. These results can prove especially helpful in planning prospective, randomized trials that will clarify the impact of widely used treatment modalities on the outcome of patients with APTE.

Age Distribution↗

Normal ventilation and ventilatory responses to chemical stimuli in juvenile mutant mice deficient in endothelin-3.

Congenital central hypoventilation syndrome (CCHS) and Hirschsprung's disease (HSCR) are often classified as neurocristopathies and are thought to share a common molecular pathogenesis related to the genes that control the development of neural crest cells. We examined whether endothelin-3 (ET-3), one of the developmental regulators of neural crest cells and of which null mutation results in aganglionic megacolon in mice, fulfills the requirements for such a common molecule. To investigate the possible involvement of ET-3 in central ventilatory control, we measured ventilation in mutant mice deficient in ET-3 by whole body plethysmography. Tidal volume and breathing frequency were measured during breathing of room air, hypoxic, hyperoxic, or hypercapnic gas mixtures in awake and anesthetized mice. There were no significant differences in resting ventilation as well as ventilatory responses to hypoxia and hypercapnia between ET-3-knockout mice and wild-type mice. Our results indicate that ET-3 can not be considered as a common pathogenic mechanism for CCHS and HSCR at least in mice.

Anesthesia↗

Incidence of beta-lactamase production and antimicrobial susceptibility of anaerobic gram-negative rods isolated from pus specimens of orofacial odontogenic infections.

The incidence of beta-lactamase production in anaerobic gram-negative rods isolated from 93 pus specimens of orofacial odontogenic infections and the antimicrobial susceptibility of these isolates against 11 antibiotics were determined. A total of 191 anaerobic gram-negative rods were isolated from the specimens. Beta-lactamase was detected in 35.6% of the black-pigmented Prevotella and 31.9% of the nonpigmented Prevotella. However, no strains among the other species isolated produced beta-lactamase. Ampicillin, cefazolin and cefotaxime showed decreased activity as regards beta-lactamase-positive Prevotella strains, whereas the activity of ampicillin/sulbactam, cefmetazole, and imipenem continued to be effective against such strains. All tested beta-lactam antibiotics were effective against Porphyromonas and Fusobacterium. Erythromycin showed decreased activity against nonpigmented Prevotella and Fusobacterium. Clindamycin, minocycline and metronidazole were powerful antibiotics against which anaerobic gram-negative rods could be tested. The present study showed that beta-lactamase-positive strains were found more frequently in the Prevotella strains than in any of the other species of anaerobic gram-negative rods. The effectiveness of adding sulbactam to ampicillin was demonstrated, as well as the difference in cephalosporin activity against beta-lactamase-positive strains.

Adolescent↗

Effects of inhaled prostacyclin analogue on chronic hypoxic pulmonary hypertension.

Inhaled PGI2 has been reported to elicit pulmonary vasodilation, but whether it is also effective in treating chronic hypoxic pulmonary hypertension is still uncertain. We designed this study to address the in vivo effectiveness of inhaled Beraprost, a stable PGI2 analogue, on pulmonary vascular tone during hypoxic exposure in normoxic (N) and chronically hypoxic (CH) rats. Pulmonary vasodilation was observed by low-dose inhaled Beraprost in N rats, but not in CH rats. It was not until higher doses of Beraprost were given that pulmonary vasodilation was obtained in CH rats. When the agent was continuously administered by an intravascular route at the inhaled dose, it elicited no vasodilation in N rats. On the contrary, it elicited profound vasodilation in CH rats, although a concomitant systemic hypotension was observed. The PGI2 receptor mRNA expression was unchanged in the lungs of CH rats compared with that of N rats. We conclude that low doses of aerosolized Beraprost may reduce pulmonary vascular tone in rats without preexisting lung diseases. In contrast, when hypoxic pulmonary hypertension is present, the threshold of Beraprost inhalation was elevated to provoke pulmonary vasodilation.

Administration, Inhalation↗

Stable pulmonary capillary haemangiomatosis without symptomatic pulmonary hypertension.

Pulmonary capillary haemangiomatosis is a rare disorder characterised by multiple angiomatous lesions composed of proliferating capillary vessels in the lung parenchyma that usually progress rapidly to establish fatal pulmonary hypertension. The 29 year old man presented here, however, has been stable for 3.5 years since the diagnosis without symptoms of pulmonary hypertension. High resolution computed tomographic findings of the pulmonary lesions seemed specific to the disease.

Adult↗

Association of tumor necrosis factor alpha gene promoter polymorphism with the presence of chronic obstructive pulmonary disease.

Tumor necrosis factor alpha (TNF-alpha), a potent proinflammatory cytokine, may be involved in the development of chronic obstructive pulmonary disease (COPD). The production of TNF-alpha is elevated in the airways of these patients. A polymorphism at position -308 of the TNF-alpha gene promoter (TNF-alpha-308*1/2) is known to be associated with alteration of TNF-alpha secretion in vitro. In this study we examined the differences in TNF-alpha-308*1/2 allele frequency to investigate the association of this polymorphism with the presence of smoking-related COPD. TNF-alpha-308*1/2 allele frequency in 106 patients (73 men and 33 women) was compared with 110 asymptomatic smoker/ex-smoker control subjects matched for sex and age and population control subjects consisting of 129 blood donors. Genotype was analyzed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic DNA isolated from peripheral blood lymphocytes. TNF-alpha-308*1/2 allele frequencies were significantly different among the groups: 0.835/0.165 in patients with COPD, 0.918/0.082 in smoker/ex-smoker control subjects, and 0.922/0.078 in population control subjects. These results indicate that TNF-alpha-308*1/2 alleles are significantly associated with the presence of smoking-related COPD.

Adult↗

The influence of fractional pulse pressure on the outcome of pulmonary thromboendarterectomy.

Although pulmonary thromboendarterectomy is an effective modality for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH), the mortality in patients with severe haemodynamic disease is still high. Recently it was reported that fractional pulse pressure (pulmonary arterial pulse pressure/mean pulmonary arterial pressure) was higher in CTEPH than in primary pulmonary hypertension (PPH). It was hypothesized that fractional pulse pressure might be low in CTEPH with inaccessible distal thrombi and/or secondary pulmonary hypertensive change, resulting to the high operative mortality. To determine the influence of fractional pulse pressure to the outcome of surgery, 32 patients with CTEPH who had thromboendarterectomy between 1985 and 1998 were studied. Pulmonary haemodynamics and fractional pulse pressure were compared between survivors (n=26) and nonsurvivors (n=6) postoperatively. Those parameters in PPH (n=18) and large vessel pulmonary arteritis (n=6) were also analysed. Fractional pulse pressure in CTEPH (1.23+/-0.21) was significantly higher than in PPH (0.93+/-0.22; p=0.0017) and lower than in pulmonary arteritis (1.69+/-0.32; p=0.03). Fractional pulse pressure in survivors (1.26+/-0.21) was significantly higher than in nonsurvivors (1.06+/-0.16; p=0.03). Fractional pulse pressure is a significant predictor for mortality in patients with high pulmonary vascular resistance >1100 dynes.sec.cm(-5). To conclude fractional pulse pressure in addition to pulmonary vascular resistance might be useful in predicting for the outcome of surgery, especially in patients with severe haemodynamic impairment.

Adult↗

The role of presenilin 1 during somite segmentation.

The Notch signalling pathway plays essential roles during the specification of the rostral and caudal somite halves and subsequent segmentation of the paraxial mesoderm. We have re-investigated the role of presenilin 1 (Ps1; encoded by Psen1) during segmentation using newly generated alleles of the Psen1 mutation. In Psen1-deficient mice, proteolytic activation of Notch1 was significantly affected and the expression of several genes involved in the Notch signalling pathway was altered, including Delta-like3, Hes5, lunatic fringe (Lfng) and Mesp2. Thus, Ps1-dependent activation of the Notch pathway is essential for caudal half somite development. We observed defects in Notch signalling in both the caudal and rostral region of the presomitic mesoderm. In the caudal presomitic mesoderm, Ps1 was involved in maintaining the amplitude of cyclic activation of the Notch pathway, as represented by significant reduction of Lfng expression in Psen1-deficient mice. In the rostral presomitic mesoderm, rapid downregulation of the Mesp2 expression in the presumptive caudal half somite depends on Ps1 and is a prerequisite for caudal somite half specification. Chimaera analysis between Psen1-deficient and wild-type cells revealed that condensation of the wild-type cells in the caudal half somite was concordant with the formation of segment boundaries, while mutant and wild-type cells intermingled in the presomitic mesoderm. This implies that periodic activation of the Notch pathway in the presomitic mesoderm is still latent to segregate the presumptive rostral and caudal somite. A transient episode of Mesp2 expression might be needed for Notch activation by Ps1 to confer rostral or caudal properties. In summary, we propose that Ps1 is involved in the functional manifestation of the segmentation clock in the presomitic mesoderm.

Alleles↗

Effect of levofloxacin on theophylline clearance during theophylline and clarithromycin combination therapy.

OBJECTIVE: To report a case of decreased theophylline clearance by the addition of levofloxacin in a patient receiving theophylline and clarithromycin. CASE SUMMARY: A 59-year-old Japanese man who was receiving theophylline for emphysema experienced stimulation, insomnia, and tachycardia due to theophylline toxicity after clarithromycin and levofloxacin were added to the regimen. The combination of these agents resulted in a decrease in theophylline clearance to approximately 60% of the initial value obtained while the patient was receiving theophylline alone. The adverse effects disappeared after the dosage was reduced and the theophylline serum concentration decreased; however, there was no change in theophylline clearance. After discontinuation of levofloxacin, the theophylline serum concentration decreased, and theophylline clearance returned to the initial level even though clarithromycin was continued. DISCUSSION: Levofloxacin is believed not to influence the clearance of theophylline, although some new fluoroquinolones have been reported to do so. This case indicates that levofloxacin and clarithromycin inhibited theophylline metabolic pathways catalyzed by both CYP1A2 and CYP3A4 and resulted in the decrease in theophylline clearance. The clearance of theophylline, therefore, is not influenced by clarithromycin alone. CONCLUSIONS: Careful monitoring is required when levofloxacin is prescribed for patients who are taking clarithromycin with theophylline.

Anti-Infective Agents↗

Clinico-epidemiological features of pulmonary histiocytosis X.

OBJECTIVE: To define the clinico-epidemiological features of pulmonary histiocytosis X in Japan. METHODS: A nationwide survey was carried out in 1997 using two questionnaires. RESULTS: The first questionnaire, which attempted to determine the number of patients during 1996, revealed that the number of patients treated at hospitals with 200 or more beds during the one-year period was estimated to be 160 (95% confidence interval: 140-180). The estimated crude prevalence among those aged 16 to 70 years was calculated as 0.27 and 0.07 per 100,000 population in males and females, respectively. The second questionnaire was concerned with the clinico-epidemiological features of the disease. Seventy-three histologically diagnosed patients were evaluated. It primarily afflicted younger adults, between the ages of 20 and 50, and showed a male predominance. Over 90% of the patients were smokers or ex-smokers and over 50% started smoking before 20 years of age, suggesting a strong association with cigarette smoking. Steroid therapy was applicable to 34% of the patients. In the patients who received steroid therapy, regression and stabilization were observed in 28% and deterioration in 36%. As for the patients for whom steroids were not required, remission occurred in 63% and progression in 10%. The ratio of remissions plus stabilization was higher in the patients who were not treated with steroids compared with those who required steroid therapy (p<0.05). CONCLUSION: In patients with pulmonary histiocytosis X therapeutic results obtained with steroids seemed not to be encouraging, although steroids are thought to be the most plausible treatment.

Adolescent↗

[Epidemiology of primary pulmonary hypertension in Japan].

Primary pulmonary hypertension(PPH) is a progressive disease of unknown etiology with poor prognosis. Recent epidemiological studies in Japan have shown that there are 230 patients (95% confidence interval: 200-260) with mean age of 41.8 +/- 18.5 years old, female to male ratio of 1.72: 1 and their median survival time was 69.0 months. At a later time, the clinically effective modalities such as lung transplantation and prostaglandin I2 for PPH were available in Japan. In 1999, the Ministry of Health and Welfare of Japan approved PPH as a objective disease of therapeutic study. Once patient is approved as PPH based on the personal clinical inquiry, Doctor's fee will be paid at the public government. This system will promote earlier and more accurate diagnosis in PPH patients and will clarify more reliable clinico-epidemiological figure of PPH in a whole territory of Japan.

Adult↗

Cell cycle-dependent regulation of TIAP/m-survivin expression.

TIAP, a murine homologue of human survivin, is a member of the inhibitor of apoptosis (IAP) family and is specifically expressed at G2/M phase of the cell cycle. To elucidate regulatory mechanisms of the cycle-dependent expression, we have analyzed the promoter region of TIAP/mouse survivin (m-survivin). The 5'-flanking region of the TIAP/m-survivin gene contained a TATA-less promoter, two AP2 sites, three NF-kB sites, one Sp1 site, many cell cycle-dependent elements (CDEs) and one cell cycle gene homology region (CHR). Primer extension and 5'-rapid amplification of cDNA ends identified one transcription start site at position -100 upstream of the ATG start site (+1). TIAP/m-survivin promoter-luciferase analysis identified a minimal promoter region within the most proximal -271 bp upstream of the ATG start site, and the region between -410 and -272 was critical for the enhancer activity. The combination between the CHR at -51 and the CDE at -57 is also essential for the cell cycle-dependent expression. Mutation of the CDE/CHR element and the enhancer elements may cause disordered expression of TIAP/m-survivin to affect cell survival and oncogenesis.

Animals↗

Noncompetitive, reversible inhibition of aminoacylase-1 by a series of L-alpha-hydroxyl and L-alpha-fluoro fatty acids: ligand specificity of aspergillus oryzae and porcine kidney enzymes.

L-lactate and L-beta-phenyllactate have been identified in the culture broth of Streptomyces sp. KY-11 as reversible noncompetitive inhibitors of Aspergillus oryzae aminoacylase-1 and porcine kidney aminoacylase I. A series of alpha-hydroxyl acids (DL-R-CH(OH)-COOH, R = Et, n-pro, n-butyl, n-pentyl, n-hexyl) also inhibited the two enzymes in reversible noncompetitive kinetics, and the inhibition potency (-log K(i)) increased with the increased hydrophobicity of the R group. The two eukaryotic enzymes showed distinct preferences to the ligand alpha-alkyl group, and the fungus enzyme was inhibited by L-beta-phenyllactate (R = benzyl) 10(3)-fold more potently than the mammalian enzyme. L-alpha-Fluoro-beta-phenyl-propionate and its D-isomer were used to show that the L-configuration of the alpha-substituent was important for potent inhibition of both the enzymes. The fungus aminoacylase-1 steeply decreased the affinity to alpha-fluoro- and alpha-hydroxy-n-caproate as pH was raised from 7 to 11, whereas the mammalian enzyme retained the affinity to these ligands under alkaline conditions. These results suggest that A. oryzae aminoacylase-1 has an acidic residue that interacts with -OH or -F, while the mammalian enzyme would have a basic residue that recognizes the alpha-substituents.

Alkylation↗

Pivotal role of CCR1-positive leukocytes in bleomycin-induced lung fibrosis in mice.

We have investigated the involvement of chemokine receptor CCR1-positive cells in bleomycin-induced lung injury, a model of pulmonary fibrosis. After bleomycin challenge in C57BL/6J mice, the expression of CCR1 mRNA increased and peaked at day 7, which paralleled to the expression of its ligands, macrophage-inflammatory protein-1 alpha and RANTES. Immunohistochemical study showed that CCR1-positive cells accumulated in the interstitial inflammatory site. Furthermore, the treatment of anti-CCR1 Ab significantly reduced the accumulation of inflammatory cells and collagen deposition, resulting in dramatic improvement of survival. These results suggest that CCR1-positive cells play significant roles in the pathogenesis of pulmonary fibrosis subsequent to bleomycin-induced lung injury, and that CCR1 could be a novel molecular target for intervention therapy against pulmonary fibrosis.

Animals↗

Characterization of bacterial orofacial infections using a new murine model.

We devised a new murine orofacial infection model using bacteria from odontogenic infection origins and characterized the experimental infections. In this model, bacteria were injected into the submandible of mice. Streptococcus constellatus and Peptostreptococcus micros produced a single abscess at the injection site and their abscess-forming and lethal abilities were low: the median abscess-forming dose (AF(50)) of S. constellatus and P. micros were 10(8.5-10.7)and 10(10.2-10.6)cfu/mouse, and their median lethal dose (LD(50)) were >11 and 10(10.6-11)cfu/mouse, respectively. Prevotella oralis and Fusobacterium nucleatum produced multiple abscesses and their abscess-forming and lethal abilities were strong: AF(50)of P. oralis and F. nucleatum were 10(6.0-6.4)and 10(7. 0-8.7)cfu/mouse, and their LD(50)were 10(7.0-7.7)and 10(8.3-9. 9)cfu/mouse, respectively. LD(50)of P. intermedia and P. gingivalis were 10(9.4->11)and 10(8.9-9.1)cfu/mouse, respectively. Prevotella intermedia and Porphyromonas gingivalis generated a necrotizing lesion, which progressed rapidly. We conclude that this murine model could reflect human orofacial odontogenic infections and is useful to investigate the pathogenicity of causative bacteria of such infections.

Abscess↗

Inhibitory mechanisms in hypoxic respiratory depression studied in an in vitro preparation.

A medullary-spinal cord preparation without the pons isolated from the neonatal rat was used to investigate the role of inhibitory neurotransmitters in the respiratory depression induced by hypoxia (hypoxic respiratory depression; HRD). The burst frequency (C(4)-f) and peak amplitudes of the integrated activity of the C(4) roots (integral C(4)) and of the hypoglossal nerve (integral XII) were recorded. A marked decrease in C(4)-f (to 36+/-6% of control, P<0. 05) with no change in the peak amplitudes of integral C(4) or integral XII was observed 17-21 min after superfusion with hypoxic CSF bubbled with 5% CO(2) in N(2). Antagonists of GABA(A) (bicuculline; 10 microM), GABA(B) (phaclofen; 0.2-0.5 mM), glycine (strychnine; 10 mM), adenosine (aminophylline; 100 mM) or opioid (naloxone; 1 mM) receptors were added to the bathing solution to block inhibitory synaptic transmission. Among these antagonists, only strychnine and naloxone alleviated HRD reducing the decline in C(4)-f to 57+/-11 and 53+/-6%, respectively (P<0.05). Posthypoxic neural arrest (PHNA) following resumption of oxygenation was shortened by the application of aminophylline, strychnine or naloxone (by 91+/-17, 96+/-25 and 40+/-6 s, respectively, P<0.05). These findings indicate that the reduction in the frequency component of HRD depends on glycinergic and opioid-mediated neuronal inhibition in an in vitro medullary spinal cord preparation. It was also observed that the duration of PHNA was positively correlated with the severity of the fall in C(4)-f (r=0.60, P<0.01).

Animals↗

The virulence of mixed infection with Streptococcus constellatus and Fusobacterium nucleatum in a murine orofacial infection model.

Orofacial infections are usually polymicrobial, and it is the microbial interactions of pathogenic species that cause tissue destruction. In this study, the microbial interaction between Streptococcus constellatus and Fusobacterium nucleatum was characterized using a murine orofacial infection model. A mixture of viable S. constellatus and F. nucleatum cells (both 2 x 10(8) CFU/mouse) was injected into the submandible; as a result, all of the test mice died. In contrast, none of the experimental animals monoinjected with either S. constellatus or F. nucleatum died (P<0.001), indicating that the synergism between the two resulted in the virulence. When a mixture of viable S. constellatus cells and a culture filtrate of F. nucleatum was tested, lethality and the bacterial cell count per lesion were significantly enhanced as compared with monoinjections (P<0.02). However, the virulence of F. nucleatum was not enhanced by infection of a culture filtrate of S. constellatus. The enhancement of virulence was observed even when viable S. constellatus cells and the culture filtrate of F. nucleatum were injected at separate sites. Heat treatment of the culture filtrate of F. nucleatum did not affect the enhancement. These results indicate that a heat-stable substance(s) produced by F. nucleatum contributes to the microbial synergy of S. constellatus and F. nucleatum in orofacial infections.

Abscess↗