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Biomedical subjects

Kunio Shirato

Publications and source records attributed to Kunio Shirato.

At least 73 records · Page 4Linked to original sources
PubMed2003

Incidence and characteristics of pulmonary thromboembolism in Japan 2000.

OBJECTIVE: The incidence of pulmonary thromboembolism (PTE) is much lower in Japan than in the United States. The number of deaths from PTE, however, has gradually increased. The present study was designed to investigate the incidence and characteristics of PTE in Japan. METHODS AND MATERIALS: We sent 5,582 questionnaires to inquire about the number of new cases of PTE between August 1, 2000 and September 30, 2000. RESULTS: We received 1,702 replies and 205 new cases were registered. The number of new cases per year was 4,022 (95% confidence interval: 3,704-4,305) and the incidence was 32 (95% confidence interval: 29.2-33.9) patients per 1,000,000 people per year. Main risk factors were immobilization, surgery, trauma, and malignancy. The mortality within a month and 6 months was 16% and 20%, respectively. Half of the deaths within a month occurred on the diagnosis day. CONCLUSION: The results showed that the incidence of PTE in Japan 2000 tended to increase compared with that in 1996, but it was still much lower than that in the United States.

Age Distribution↗
PubMed2003

Recent developments in diagnostic imaging techniques and management for acute pulmonary embolism: multicenter registry by the Japanese Society of Pulmonary Embolism Research.

OBJECTIVE: There are many reports on the diagnosis and management of acute pulmonary embolism (APE), but there have been no investigations concerning the actual conditions in which recent developments in diagnostic imaging techniques and therapies have been applied in clinical practice. The present study was designed to investigate the changes in diagnostic imaging techniques and therapies for APE. METHODS AND PATIENTS: Three hundred and nine APE patients diagnosed during January 1994-October 1997 (Group 1) were compared with 257 APE patients diagnosed during November 1997-October 2000 (Group 2) in terms of the diagnostic imaging techniques and therapies for APE. RESULTS: Compared with Group 1, pulmonary angiography and contrast-enhanced computed tomography were more frequently performed for diagnosis in Group 2 [45.3% vs 56.8% (p = 0.0069) and 13.9% vs 57.6% (p < 0.0001), respectively]. Heparin and vena cava filter were used more often in Group 2 [74.4% vs 82.1% (p = 0.033) and 18.4% vs 33.9% (p < 0.0001), respectively]. The frequency of thrombolytic therapy was unchanged between the two groups. Warfarin use in discharged patients increased from 71.9% to 83.8% (p = 0.0022). However, the examination rates for deep vein thrombosis (DVT) were low (60.8% in Group 1 and 65.4% in Group 2, p = 0.29) and unchanged using any imaging techniques. CONCLUSION: The diagnostic imaging techniques for APE increased in variety and the management has improved, while the diagnosis for DVT remains unchanged.

Acute Disease↗
PubMed2003

[The epidemiology of acute pulmonary thromboembolism].

In contrast to the decreasing incidence of pulmonary thromboembolism in Western countries, the incidence examined as determined by autopsy, vital statistics, and clinical surveys is increasing in Japan. The combination of these data indicates the possibility of low diagnostic ability in Japan. The causes of the disease and the predictors of in-hospital death are summarized. The most popular congenital coagulopathies in Western countries, factor V Leiden and prothrombin G20210A mutation, have not been found in Japan. But recent reports showed that coagulopathy might have a greater contribution to the occurrence of the disease than was previously thought. We introduce reports that show a relation between the disease and life style.

Acute Disease↗
PubMed2002

Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness.

Histamine has a variety of airway actions and is considered to be an important mediator in asthma. This study examined the role of endogenous histamine in allergic airway eosinophil recruitment and hyperresponsiveness using L-histidine decarboxylase gene knockout mice. Histamine levels of the airways in L-histidine decarboxylase knockout mice were largely diminished compared with wild-type mice. Inhalation challenge with ovalbumin (OVA) in OVA-sensitized wild-type mice caused eosinophil accumulation in the lung as well as airway hyperresponsiveness to methacholine 3 days after the challenge. The eosinophil recruitment was significantly reduced in the knockout mice. In the bone marrow, the proliferation of eosinophils was enhanced after OVA challenge in the wild-type mice; however, the proliferation was significantly reduced in the knockout mice. The induction of P-selectin in the lung after OVA challenge was also inhibited in the knockout mice. In contrast, airway hyperresponsiveness was not suppressed in the knockout mice. These results suggest that endogenous histamine is involved in the accumulation of eosinophils into the airways after allergic challenge, possibly acting in the bone marrow and producing P-selectin in the airways. Furthermore, allergen-induced airway hyperresponsiveness appeared to occur independently of airway eosinophilia in our present model.

Administration, Inhalation↗
PubMed2002

Differential effect of epidermal growth factor on serous and mucous cells in porcine airway submucosal gland.

Using a patch-clamp technique, we found that the fresh porcine submucosal gland acinar cells contained two functionally distinct cell populations, i.e. physiologically relevant concentration of acetylcholine (ACh, 30 nM) induced two distinct patterns of electric response in tracheal gland acinar cells. One was characterized by an outstanding oscillatory Cl(-)-current activity, and the other was with poor Cl(-)-current response but with a comparable K(+)-current. We examined the effect of epidermal growth factor (EGF) on the ACh-induced electric responses in these cells. EGF affected only the latter (K(+)-prominent) cell type to potentiate significantly the ACh-induced K(+)-current. An immunohistochemistry revealed that the receptor for EGF was identified preferentially on the mucous, but not serous, cells. Genistein, one of the tyrosine-kinase inhibitors, abolished the augmentation effect of EGF on the ACh-induced current. Thus, we identified the serous cell with a Cl(-)-rich current in response to ACh and the mucous cell with a K(+)-dominant response. Moreover, EGF affected the mucous cells alone to potentiate the ACh-induced electric response. EGF may contribute to the pathophysiological alterations in chronic inflammatory airways both in morphological (mucous cell hypertrophy/hyperplasia) and functional (thick viscous hypersecretion) ways.

Acetylcholine↗
PubMed2002

Vasodilator signals from the ischemic myocardium are transduced to the coronary vascular wall by pertussis toxin-sensitive G proteins: a new experimental method for the analysis of the interaction between the myocardium and coronary vessels.

OBJECTIVES: We sought to detect cross-talk between the beating heart and coronary vascular bed during myocardial ischemia and to test the hypothesis that the cross-talk is mediated by pertussis toxin (PTX)-sensitive G proteins (G(PTX)) in vessels. BACKGROUND: Coronary flow is closely related to the myocardial metabolic state, indicating the existence of a close interaction between cardiac muscle and coronary vascular beds. Experimental methods for the analysis of the interaction, however, have not been established. METHODS: Coronary detector vessels (DVs) were isolated from rabbit hearts. One end of the vessel was cannulated to a micropipette, and the other end was ligated. After the DV was pressurized (60 cm H(2)O), it was gently placed on the myocardium, which was perfused by the left anterior descending coronary artery (LAD) of anesthetized, open-chest dogs (n = 23). The LAD was occluded, and the DV diameter was observed using an intravital microscope with a floating objective system. To evaluate the involvement of G(PTX), the DV was pre-incubated with PTX (100 ng/ml). RESULTS: The LAD occlusion of the beating heart produced significant dilation of DVs (241 +/- 25 microm) by 10%. The DVs pretreated with PTX (250 +/- 27 microm) did not dilate in response to myocardial ischemia. N(omega)-nitro-L-arginine (100 micromol/l), but not glibenclamide (5 micromol/l), abolished the ischemia-induced DV dilation. CONCLUSIONS: We have established experimental methods for direct analysis of the interaction between the myocardium and coronary microvessels. We conclude that the ischemic myocardium releases transferable vasodilator signals that are transduced by means of the G(PTX) located in the vascular walls. The nitric oxide pathway is involved in the signal transduction.

Animals↗
PubMed2002

Effect of angiotensin converting enzyme inhibition on myocardial phosphoinositide metabolism visualised with 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol in myocardial infarction in the rat.

We recently reported that myocardial phosphoinositide (PI) metabolism can be visualised by 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in rats with myocardial infarction (MI). Angiotensin II, the receptors for which are expressed predominantly in infarcted areas with active fibrogenesis rather than in non-infarcted regions, is involved in the upstream signalling systems of PI metabolism and plays an important role in the process of left ventricular (LV) remodelling after MI. We therefore hypothesised that the distribution of 11C-DAG after MI may be affected by the inhibition of angiotensin converting enzyme, which is one of the most important factors in the development of LV remodelling after MI. Rats were injected with 11C-DAG after 3 or 10 weeks of treatment with captopril or no treatment following coronary artery ligation, and quantitative autoradiography was performed. Cells occupying the infarcted region were identified by immunohistochemistry. Compared with untreated rats, treatment with captopril for 3 weeks after MI elicited a reduction in the 11C-DAG uptake in the infarcted region (P<0.05) but not in the non-infarcted region, and was associated with a 22% decrease in the heart weight/body weight ratio. The thallium-201 distribution in the infarcted area was similarly low in the rats with and rats without the 3-week captopril treatment after MI. Abundant macrophages and myofibroblasts occupied the infarcted area in both rats with and rats without the captopril treatment for 3 weeks after MI. The 11C-DAG radioactivity in the infarcted region in the untreated rats was lower 10 weeks after MI than 3 weeks after MI (P<0.01). This finding was in agreement with the results of immunohistochemistry demonstrating that the number and size of macrophages and myofibroblasts were remarkably reduced in rats 10 weeks after MI compared with 3 weeks after MI. Captopril treatment for 10 weeks after MI did not decrease the 11C-DAG radioactivity in the infarcted area further. These data suggest that 11C-DAG is useful for visually detecting regions with activated PI metabolism after MI, and that captopril reduces PI metabolism in the infarcted region in the relatively early phase of MI, which might contribute to the attenuation of ventricular remodelling.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Pulmonary hypertension in patients with chronic obstructive pulmonary disease: recent advances in pathophysiology and management.

In patients with chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH) is associated with a worse prognosis. Recently, information has been increasing concerning the cellular and molecular aspects of the pathophysiology of PH in COPD. The most striking finding is the role of vascular endothelial cells and endogenous mediators released by these cells. Endothelial cell-dependent relaxation is impaired in COPD patients with PH. Moreover, vascular remodelling in these patients is mainly responsible for irreversible PH in advanced COPD. Smoking cessation will slow down the progression of the disease process and may prevent the development of PH in COPD. The timing of initiation of long-term oxygen therapy is important for the effective management of PH in COPD. Research on therapeutic agents for the effective treatment of PH is still needed in the management aspect of patients with COPD. This review focuses on the recent advances in our understanding of the pathophysiology and treatment of PH in COPD.

Cardiac Catheterization↗
PubMed2002

The control effect of histamine on body temperature and respiratory function in IgE-dependent systemic anaphylaxis.

BACKGROUND: The systemic anaphylaxis reaction comprises various symptoms, including hypotension, changes in respiration pattern, and hypothermia. OBJECTIVE: To elucidate the role of histamine in each of these symptoms, we induced the passive systemic anaphylaxis reaction in histidine decarboxylase gene knockout (HDC [-/-]) mice, which lack histamine. METHODS: HDC(-/-) mice were generated by knocking out the HDC gene, which codes for the unique histamine-synthesizing enzyme. Twenty-four hours after the injection of IgE, HDC(+/+) and HDC(-/-) mice were injected with allergen and body temperature, blood pressure, and respiratory function were monitored in each mouse. RESULTS: Blood pressure dropped in both the HDC(-/-) mice and the HDC(+/+) mice. In contrast, respiratory frequency dropped and the expiratory respiration time was elongated only in the HDC(+/+) mice. Body temperature was decreased in the HDC(+/+) mice and was practically unchanged in the HDC(-/-) mice. Histamine receptor antagonists blocked the body temperature drop in the HDC(+/+) mice. Intravenous histamine induced similar patterns of body temperature decrease in the HDC(+/+) mice and the HDC(-/-) mice. Mast cell-deficient W/W (v) mice did not show the decrease in body temperature; this suggests that the histamine that contributed to the decrease in body temperature was derived from mast cells. CONCLUSION: According to the results of this investigation, in the passive systemic anaphylaxis reaction, respiratory frequency, expiratory time, and body temperature are shown to be controlled by the activity of histamine, but its contribution to blood pressure is negligible.

Allergens↗
PubMed2002

Normal and oxidized low density lipoproteins accumulate deep in physiologically thickened intima of human coronary arteries.

Diffuse intimal thickening (DIT) that develops as a physiologic adaptation in the arterial wall has been implicated to have a predilection for atherosclerosis. We histologically investigated the lipid accumulation process in the human coronary DIT by focusing on the localization of normal and oxidized low-density lipoproteins (LDLs). Immunohistochemistry for apolipoprotein B 100 (a major apolipoprotein of LDL) and 8-iso-prostaglandin F(2alpha) (an oxidative product in LDL) showed substantial accumulation of oxidized relative to normal LDLs in the deep layers of DIT (52/139 segments). Subendothelial deposition of normal rather than oxidized LDLs, known as an early event of fatty streak formation, was less frequently found (13/139 segments). In contrast with fibrofatty lesions, lipid accumulation localized deep in DIT was characterized by fine lipid droplets scattered in the preserved tissue and by its association with neither macrophage accumulation nor apoptosis in the constituent cells. On the other hand, the deep intimal location of lipid accumulation clearly coincided with increased type I and type III collagen and elastic fibers but rarely with sulfated proteoglycans including decorin, which were all strongly expressed in advanced lesions. This lipid accumulation was found only in sites with DIT of more than 200 micro m, occasionally extending to the inner media and involving neovessel formation around it. The presence of deep intimal lipid accumulation was associated with reduced endothelium-dependent relaxation to substance P in isolated coronary rings. These results suggest that normal and oxidized LDLs accumulate preferably in the nutritional border zone of established DIT involving local extracellular matrix alterations but independently of inflammatory or apoptotic processes. This may contribute to the functional and morphologic abnormalities seen in human coronary atherogenesis that progresses slowly with age.

Adult↗
PubMed2002

Increasing mortality from pulmonary embolism in Japan, 1951-2000.

In the United States, annual mortality rates from pulmonary embolism (PE) tended to increase from the 1960s to the mid 1980s, but thereafter began to decrease. In Japan, PE is not yet widespread and there have not been any reports of the time-trend of its mortality rate. The present study calculated the annual age-adjusted and age-specific PE mortality rates for Japanese residents during 1951 to 2000 from the 'Vital Statistics of Japan' and the census data and population estimates for the intercensal years. Throughout the study period, the age-adjusted deaths and mortality rates from PE continued to increase, and between 1976 and 1996 the increases in the annual age-specific mortality rates were substantial in males 45-49 years of age and 55 years or older, and in females 30 years of age or older. The age-specific PE death rates increased throughout the life span in general and according to the decade. Male mortality was greater at most ages. In Poisson regression analysis, the relative risk of death from PE was increased in males, the aged, and in recent years. Overall, mortality from PE in Japan increased significantly during 1951 to 2000.

Adolescent↗
PubMed2002

Right ventricular ejection function assessed by cineangiography--Importance of bellows action.

The right ventricular ejection fraction (RVEF) can be shown theoretically as a mathematical function of the percent shortening in the 3 axial dimensions of the right ventricular cavity (the septum-free wall dimension (SF), the anterior-posterior dimension (AP), and the tricuspid valve-apex dimension (TA) or the long axis dimension (LA)). There is a need to decide which mechanism is the most important for the RVEF in cases with neither obvious regional wall motion abnormalities of the left ventricle nor right ventricular overload. Forty-four consecutive subjects (34 males/10 females) were enrolled: 16 had normal hemodynamic parameters without significant coronary artery stenosis, 15 had hypertrophic cardiomyopathy and 13 had dilated cardiomyopathy. Biplane right ventricular cineangiography was performed and the percent shortening of the SF, AP, and TA or LA were measured. The percent shortening in the SF (34.8+/-14.7%) was larger than that of the AP, TA, and LA (23.2+/-8.5, 21.0+/-8.3 and 18.3+/-7.0, respectively; all p<0.001). There was a linear correlation between the percent shortening of each dimension and the RVEF. The 95% confidence interval of the regression equation from the percent shortening of the SF and RVEF was located above those from the other percent shortenings, except for a lower RVEF. These results indicate that systolic shortening of the SF (ie, bellows action) plays an important role in the RVEF except for a lower ejection fraction.

Adolescent↗
PubMed2002

Evaluation of heart-rate turbulence as a new prognostic marker in patients with chronic heart failure.

The significance of heart-rate turbulence (HRT) in patients with chronic heart failure (CHF) was evaluated to examine whether it is sensitive to the risk of ventricular tachycardia (VT). HRT is reported to predict the prognosis after myocardial infarction (MI), but its prognostic value in patients with CHF remains unknown. HRT was measured in 50 CHF patients (left ventricular ejection fraction <50% and/or left ventricular end-diastolic diameter >55 mm, 34 cardiomyopathy, 16 post-MI) and 21 patients without obvious heart diseases (control). HRT slope and HRT onset were measured by the original definitions using digitized Holter ECG recordings. Cardiac pump function was assessed by echocardiography. The value of the HRT slope was significantly lower in CHF than in control (3.7 +/- 1.7 vs 16.4 +/- 5.3, mean +/- SD, p < 0.01). The value of the HRT onset in patients with CHF was significantly higher than that in control patients (-1.1 +/- 1.9 vs -3.6 +/- 1.7, mean +/- SD, p < 0.05). The HRT slope and onset in CHF patients with VT were nearly identical to those without VT. The HRT slope appears to be a powerful prognostic marker that shows significant differences between CHF subgroups when divided by clinical events; that is, CHF death and CHF hospitalization. However, it has limited value for predicting fatal ventricular arrhythmias.

Adult↗
PubMed2002

Systolic heterogeneity of transmural myocardial function in normal subjects: physiological functional heterogeneity.

Because of the lack of a clinical method for assessing the transmural myocardial function, few studies on the heterogeneity during the myocardial contraction/relaxation sequence inside the human ventricular wall have been reported, despite the fact that the importance of the pathophysiology in the transmural heterogeneity has been stressed in previous experimental studies. We studied the transmyocardial functional heterogeneity of the basal anteroseptal segment in normal subjects (n = 8, 40.0 +/- 12.8 year, male), adopting the novel high resolution Doppler measurement "Phased Tracking Method". Each transmural layer of 0.75 mm thickness showed functional heterogeneity (physiological transmural functional heterogeneity), namely larger thickening occurred in the left ventricular endocardial side (right side 1/3: 26.1 +/- 5.2% of the total wall thickness, middle 1/3: 31.9 +/- 2.7%, left side 1/3: 42.1 +/- 6.4%) and the peak thickening shifted smoothly in time from the middle layers to the left subendocardial side during the contraction period. We concluded that transmural functional heterogeneity does exist in normal subjects as well as in the experimental animals of previous reports. Smooth and coordinate myocardial layer contraction across the ventricular wall (physiological transmural functional heterogeneity) is fundamental to maintain the normal ventricular function.

Adult↗
PubMed2002

Post-endsystolic active shortening in the non-ischemic region impairs left ventricular pressure fall in acute ischemic heart.

To investigate the relation between the impairment of isovolumic relaxation and the regional wall motion in acute ischemia, the left ventricular pressure fall and regional myocardial motion were examined in the relaxation phase in dogs during both acute coronary artery occlusion (n = 12) and a regional coronary flow reduction (n = 6). Fifteen to 40 seconds after complete coronary artery occlusion or in the stable state after a regional coronary flow reduction by 70 to 90% of the control state, a shortening of the non-ischemic region at the early isovolumic relaxation phase (the post-endsystolic shortening) appeared, combined with lengthening of the ischemic region. In these situations, the logarithmic plots of the left ventricular pressure fall was composed of two components (time constant of early part [Ta] and at latter part [Tb]). Ta was greater than Tb (64.3 +/- 13.8 milliseconds vs. 36.6 +/- 10.4 milliseconds at 15 seconds after coronary occlusion, p < 0.01; 67.6 +/- 22.9 milliseconds vs. 45.1 +/- 17.5 milliseconds at flow reduction, p < 0.01) and the time constant at control (p < 0.01). These findings suggested that post-endsystolic shortening in the non-ischemic region played a role in a the non-uniformity of the left ventricular contraction and contributed to the impairment of the left ventricular pressure fall in acute regional ischemia, especially in early isovolumic relaxation.

Acute Disease↗
PubMed2002

Hemodynamic effects of inhaled nitric oxide using pulse delivery and continuous delivery systems in pulmonary hypertension.

OBJECTIVE: Inhaled nitric oxide (NO) has been used for pulmonary vasodilation therapy in patients with pulmonary hypertension. Inhaled NO for awake and ambulatory patients, however, is unusual because it requires intubation or a tightly fitting facemask, and a large-scale delivery system for the safe management of toxic nitrogen oxides. We undertook this study to investigate the possibility of using inhaled NO therapy for awake and ambulatory patients with pulmonary hypertension. METHODS: Patients with pulmonary hypertension underwent cardiac catheterization and hemodynamic variables were measured at the baseline, after inhaled NO using our pulse delivery system, which involved a nasal cannula and a pulse device, and after inhaled NO using a continuous delivery system. PATIENTS OR MATERIALS: We studied seventeen patients with precapillary pulmonary hypertension (4 men and 13 women; age, 41+/-3, ranging from 19 to 61). RESULTS: Cardiac output was increased significantly by each system. Pulmonary vascular resistance was decreased significantly by each system. There was no significant change in mean pulmonary artery pressure, mean systemic artery pressure, or systemic vascular resistance. The concentrations of NO and nitrogen dioxide (NO2) in the expiratory gas using the pulse delivery system were 0.0 ppm as long as the pulse device was synchronized with the patient's respiratory cycle. CONCLUSION: Inhaled NO using our pulse delivery system changed the hemodynamic variables similarly to those when using the continuous delivery system. The concentrations of NO and NO2 in the expiratory gas using the pulse delivery system were within safe limits.

Administration, Inhalation↗
PubMed2002

Effects and problems of continuous infusion of epoprostenol for patients with primary pulmonary hypertension.

OBJECTIVE: We examined the usefulness and the problems of epoprostenol (Epo) therapy in adult Japanese with primary pulmonary hypertension (PPH). SUBJECTS AND METHODS: In eleven cases with PPH, both acute and chronic effects, and clinical effects of Epo were assessed. RESULTS: In the acute challenge test (n = 6), Epo reduced both systemic and pulmonary vascular resistance and increased the cardiac output, but did not change the ratio of pulmonary to systemic vascular resistance, while the systemic and pulmonary blood pressure also did not change. In the chronic study (n = 9), Epo decreased the pulmonary blood pressure without changes in systemic blood pressure, and increased the cardiac output. Both systemic and pulmonary vascular resistance decreased with a decrease in the ratio of the pulmonary to systemic vascular resistance. The level of brain natriuretic peptide and atrial natriuretic peptide, NYHA functional class and 6-minute walking distance were improved by Epo therapy. In spite of Epo therapy, two patients did not improve and died. Another patient improved in terms of symptoms but then died suddenly from massive lung bleeding. Two patients who improved physically could not be discharged because of psychiatric problems. One patient underwent lung transplantation. Five out-patients have been continuing Epo therapy. CONCLUSION: We demonstrated that the chronic effect of Epo treatment is sufficient even at the dose used in our hospital. However, it was shown that there was resistance to this therapy in some of the cases and that we should pay attention to the severe adverse effects of Epo.

Adult↗