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Biomedical subjects

K Kawamura

Publications and source records attributed to K Kawamura.

At least 181 records · Page 10Linked to original sources

Early detection of successful coronary reperfusion based on serum concentration of human heart-type cytoplasmic fatty acid-binding protein.

Both human heart-type cytoplasmic fatty acid-binding protein (H-FABPc) and myoglobin are low molecular weight proteins that are abundant in the cytoplasm of myocardial cells. Unlike myoglobin, H-FABPc content in the skeletal muscle is less than in cardiac muscle. To investigate the usefulness of the serum concentration of H-FABPc in the early detection of successful coronary reperfusion, we measured serum concentrations of H-FABPc and myoglobin in 45 patients with acute myocardial infarction treated with intracoronary thrombolysis or direct percutaneous transluminal coronary angioplasty. Coronary angiography was performed every 5 min for reperfusion therapy to identify the onset of reperfusion. Reperfusion, defined as a TIMI grade 2 or 3, was achieved within 60 min of the initiation of reperfusion therapy in 30 patients (the reperfused group), but was not achieved in 15 patients (the non-reperfused group). Blood samples were obtained before initiation of treatment and 15, 30 and 60 min after initiation of treatment in the non-reperfused group. In the reperfused group, samples were obtained before reperfusion and 15, 30 and 60 min after reperfusion. The H-FABPc ratio (the ratio of value after to value before the initiation of treatment or reperfusion) increased sharply after the onset of reperfusion, peaking at 41 +/- 18 min, and decreased rapidly thereafter. The predictive accuracy of an H-FABPc ratio of > 1.8 for the detection of reperfusion within 60 min of the initiation of treatment was 93% at 15 min after reperfusion, 98% at 30 min, and 100% at 60 min. Similar rates of predictive accuracy were observed for a myoglobin ratio > 2.4. The H-FABPc ratio detected successful reperfusion as early as 15 min after the onset of reperfusion and was highly accurate in detecting reperfusion within 60 min of the onset of reperfusion. The predictive accuracy of the H-FABPc ratio was similar to that of the myoglobin ratio for the early detection of successful coronary reperfusion.

Adult↗

Immunohistochemical localization of neurocan and L1 in the formation of thalamocortical pathway of developing rats.

We used immunohistochemistry to examine possible molecular interactions between the subplate and growing thalamocortical axons in rat fetuses. In the cortical anlage of embryonic day 16 (E16), the subplate first appeared below the cortical plate. Among chondroitin sulfate proteoglycans, phosphacan was uniformly distributed throughout the cortical wall, whereas neurocan was localized only in the subplate at E16. Neural cell adhesion molecules, NCAM-H, TAG-1, and L1, were detected in the cortical anlage. Both cortical neurons and growing axons were diffusely immunopositive for NCAM-H, and TAG-1 immunoreactivity was found on immature neurons and cortical efferent axons but not on thalamocortical axons. L1 immunoreactivity was specifically localized on the growing thalamocortical axons. When the locations of neurocan and L1 were compared in the developing cortex, L1-bearing axons were found to extend to neurocan-immunopositive regions; neurocan immunoreactivity was intense in the subplate at E16, when small numbers of L1-immunoreactive thalamocortical axons began to invade the cortex. At E17, many L1-positive axons were observed in the subplate that expressed neurocan specifically. Double immunostaining showed that L1-positive axons and neurocan immunoreactivity overlapped in the subplate at E17. After E18, neurocan expression gradually extended to the lower part of the cortical plate; it extended to the entire cortex by E21, 1 day before birth. By E21, L1-bearing axons had invaded the lower part of the cortical plate. The present study demonstrated that the neurocan expression precedes growth of L1-bearing thalamocortical afferent fibers. Because neurocan can bind to L1 molecule in vitro, these results suggest that neurocan and L1 play some important roles in pathfinding of the thalamocortical afferent fibers during rat corticogenesis.

Animals↗

Thrombopoietin enhances proliferation and differentiation of murine yolk sac erythroid progenitors.

Thrombopoietin (TPO), the ligand for the receptor proto-oncogene c-Mpl, has been cloned and shown to be the critical regulator of proliferation and differentiation of megakaryocytic lineage. Initially, TPO was not considered to have the activity on hematopoietic lineages other than megakaryocytes. Recently, however, TPO was reported to enhance the in vitro erythroid colony formation from human bone marrow (BM) CD34+ progenitors or from mouse BM cells in combination with other cytokines. We examined the effects of TPO on the colony formation of hematopoietic progenitors in mouse yolk sac. TPO remarkably enhanced proliferation and differentiation of erythroid-lineage cells in the presence of erythropoietin (Epo). This effect was observed even in the absence of Epo. Compared with adult BM, yolk sac turned out to have relatively abundant erythroid and erythro-megakaryocytic progenitors, which responded to TPO and Epo stimulation. TPO similarly stimulated erythroid colony formation from in vitro differentiation-induced mouse embryonic stem (ES) cells whose hematopoietic differentiation status was similar to that of yolk sac. These findings help to understand the biology of hematopoietic progenitors of the early phase of hematopoiesis. Yolk sac cells or in vitro differentiation-induced ES cells would be good sources to analyze the TPO function on erythropoiesis.

Animals↗

Is CD36 deficiency an etiology of hereditary hypertrophic cardiomyopathy?

Hereditary hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, but the genetic defects are still unclear in many cases. Reduced myocardial long-chain fatty acid (LCFA) uptake has been demonstrated in patients with some types of HCM. In addition, a possible relationship between a shift ofmyocardial substrate utilization and cardiac hypertrophy has been suggested by experimental studies. Myocardial uptake of LCFAs occurs via a specific transporter, which is homologous with human CD36. CD36 deficiency has also been reported in some individuals, and is transmitted as an autosomal dominant trait like HCM. In this study, we analyzed CD36 in 47 patients with HCM [29 with asymmetric septal hypertrophy (ASH) and 18 without ASH], 11 patients with dilated cardiomyopathy (DCM), and 26 patients with pressure-overload cardiac hypertrophy. Eleven patients (37.9%) who had HCM with ASH, one (9.1%) with DCM, and two (7.7%) with pressure-overload hypertrophy showed CD36 deficiency, while none of the HCM patients without ASH had CD36 deficiency. One patient who had HCM with ASH and CD36 deficiency showed no myocardial LCFA uptake, although myocardial perfusion was normal. Reduced myocardial LCFA uptake despite normal myocardial perfusion was demonstrated in the other HCM patients with ASH and CD36 deficiency. Based on the high prevalence of CD36 deficiency in HCM patients with ASH, we hypothesize that this deficiency might be one etiology of hereditary HCM.

Adult↗

Evolution to dilated cardiomyopathy from acute eosinophilic pancarditis in Churg-Strauss syndrome.

We describe the clinical manifestations of a patient with Churg-Strauss syndrome who presented with severe acute cardiac involvement and whose disease evolved to dilated cardiomyopathy (DCM), with special reference to the histopathological findings. Endomyocardial biopsies, conducted sequentially, three times within 10 months, revealed severe eosinophilic endomyocarditis in the acute phase, interstitial fibrosis in the subacute phase, and endocardial thickening with mural thrombi, at 10 months. Although acute inflammation associated with elevation of eosinophil granule proteins subsided with steroid therapy, left ventricular dilatation with reduced contractility progressed. A subgroup of DCM is not considered to be idiopathic but, rather, an aftereffect of hypereosinophilic heart disease.

Acute Disease↗

Ultrastructural changes during myocardial hypertrophy and its regression: long-term effects of nifedipine in adult spontaneously hypertensive rats.

Nifedipine (20 mg/kg/day) was given to 15-week-old spontaneously hypertensive rats for 20 weeks (SHR-N, n = 8). Comparison was done with sex-matched 15-week-old SHR (SHR-15, n = 7), untreated 35-week-old SHR (SHR-C, n = 10), 15-week-old normotensive Wistar-Kyoto rats (WKY-15, n = 15), and 35-week-old WKY (WKY-15, n = 5). Light and electron microscopic data on the subepicardial, middle and subendocardial layers and papillary muscles of the left ventricle were compared among the five rat groups. In SHR-N, blood pressure was significantly reduced by nifedipine, but was higher than in WKY-35 (199 +/- 11 mmHg vs 121 +/- 13 mmHg). The left ventricular weight/body weight ratio was much lower in SHR-N than in SHR-C, and was even below the baseline value in SHR-15. In addition, cardiac myocyte diameter was much smaller in each myocardial layer of SHR-N than in SHR-C, and was similar to the findings in SHR-15, but still larger than in WKY-35. The interstitial area ratio was markedly reduced in SHR-N and did not differ from that in SHR-15 or even WKY-15, while capillary density was significantly greater than in SHR-C and comparable to that in WKY-35. In SHR-C, large fibrotic foci were common, and many hypertrophic cardiac myocytes showed various degenerative changes including those of mitochondria and widening of the intermyofibrillar spaces. These changes were rarely seen in SHR-N. The intracellular volume ratio of myofibrils did not differ between SHR-N and WKY-35, but was significantly decreased in SHR-C, whereas that of mitochondria did not differ between SHR-N and SHR-C or WKY-35. These findings indicate that despite only a moderate suppression of hypertension, long-term nifedipine treatment caused regression of left ventricular hypertrophy, with cardiocyte hypertrophy, interstitial fibrosis, degenerative changes, and subcellular remodeling being reversed to the baseline levels in SHR-15. In addition, the capillary density was increased to that seen in WKY-35.

Animals↗

Iodine-123 metaiodobenzylguanidine myocardial scintigraphy for prediction of response to beta-blocker therapy in patients with dilated cardiomyopathy.

This study was performed to evaluate whether iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy could predict the response to beta-blocker therapy in patients with nonischemic dilated cardiomyopathy (DCM). Beta-Blocker therapy is effective in some patients with DCM. MIBG myocardial scintigraphy has also been suggested to be useful in evaluating the severity of myocardial damage in DCM. However, no data exist on whether MIBG imaging can be used to predict which patients with DCM will respond to beta-blocker therapy. We prospectively evaluated whether MIBG myocardial imaging was useful in predicting responses to beta-blocker therapy in patients with DCM. MIBG imaging was performed in 45 patients with DCM (35 men, 10 women, aged 13 to 68 years) before the start of bisoprolol. The heart to mediastinum (H/M) MIBG uptake ratio was evaluated on initial and delayed images, and the percent washout rate of myocardial MIBG was also obtained from these data. Of the 45 patients, 30 (67%) responded to beta-blocker therapy, whereas 2 were resistant and 13 showed progression of heart failure or died of heart failure. By logistic regression analysis, the H/M uptake ratio on delayed images was seen to be a good predictor of the response to beta-blocker therapy with a threshold of 1.7 (sensitivity = 91%, specificity = 92%, accuracy = 91%, positive and negative predictive value = 97% and 80%, respectively). These results indicate that an H/M ratio > 1.7 on the delayed MIBG myocardial scintigraphic images provides a useful indication of whether patients with DCM will respond to beta-blocker therapy.

3-Iodobenzylguanidine↗

Do repolarization abnormalities in hypertrophic cardiomyopathy represent impaired fatty acid utilization? An observation with QRST isointegral maps.

To identify the clinical significance of the isointegral body surface map of the QRST interval (QRST map) and the occurrence of repolarization abnormalities in patients with hypertrophic cardiomyopathy (HCM), the QRST map and signal-averaged electrocardiogram were evaluated in 50 patients with HCM, in 33 of whom the results were compared with nuclear images both for radioiodine-labeled fatty acid metabolism and for radiothallium perfusion. The QRST departure map was used to determine two parameters of difference between patient and control recordings: the subnormal area (the number of lead points at which the departure index values were negative and lay more than 2 SDs from the mean of the normal control group) and the subnormal minimum (the absolute value of the minimum in the departure map). Late potentials were detected in 6 (12%) of the 50 patients; they were observed in 3 of the 5 patients with dilated-phase HCM but in only 3 (7%) of the other 45 patients. The subnormal area and minimum values were lower in nonobstructive HCM than in dilated-phase HCM. Of the 33 patients examined by myocardial imaging, 28 (33%) had a filling defect or decreased uptake, as shown on fatty acid metabolic images, and 10 of the 28 also showed abnormal myocardial perfusion images, while the 18 others showed normal perfusion images. These 28 patients showed significantly larger values of the subnormal area and minimum than patients with normal results in both image tests, regardless of whether or not myocardial perfusion imaging abnormalities were present. The localization of filling defects or of decreased uptake presented in fatty acid metabolic images corresponded to the position of the minimum on the QRST departure map. These results suggest that the QRST map is useful for detection of repolarization abnormalities in HCM and that these abnormalities are highly related to impaired fatty acid utilization of the myocardium.

Adolescent↗

Impaired expression of neural cell adhesion molecule L1 in the extrinsic nerve fibers in Hirschsprung's disease.

Immunohistochemical studies on the ganglionic and aganglionic segment in Hirschsprung's disease (HD) were carried out using antibodies against three neural membrane proteins, Thy-1, integrin alpha5, and L1. Enteric neural elements were immunostained with antibodies against neurofilament, which is the neuronal cytoskeletal protein. In ganglionic segments, neurofilament-immunoreactivity was detected in neuronal cell bodies and fine nerve fibers of the myenteric and submucosal plexuses. All of these neural elements were immunopositive for Thy-1, integrin alpha5, and L1. In aganglionic segments, no intrinsic neurons were detected, and instead, hypertrophied nerve bundles were observed in intermuscular space, in submucosa, and in circular muscle layer by immunochemistry for neurofilament. These hypertrophied nerve bundles were immunopositive with anti-Thy-1 and anti-integrin alpha5 antibodies. However, they were not immunostained with anti-L1 in all five cases. These findings indicate that the expression of L1 molecule, which plays an important role in cell adhesion, neural cell migration, and neurite outgrowth, is impaired in the extrinsic nerve fibers in aganglionic colon. And this may perturb neural crest migration and adequate neurite outgrowth, with resulting aganglionic segment and abnormal nerve bundles of extrinsic fibers in HD.

Antigens, CD↗

Left ventricular Doppler filling pattern in dilated cardiomyopathy: relation to hemodynamics and left atrial function.

This study attempted to examine the relation of left ventricular filling patterns to hemodynamic status and left atrial function in dilated cardiomyopathy. Transesophageal echocardiography and cardiac catheterization were performed in 41 patients with dilated cardiomyopathy (six with an ischemic origin). Transmitral, left atrial appendage, and pulmonary venous flow velocities were recorded with the pulsed Doppler method. Left atrial systolic function was assessed by the peak velocity of the left atrial appendage emptying wave and pulmonary venous flow reversal during atrial systole. Patients were classified into three groups according to their left ventricular filling patterns. Group 1 showed an abnormal relaxation pattern (E wave/A wave ratio <1, n = 17), group 2 had a normal or pseudonormal pattern (1 < or = E/A < 2, n = 11), and group 3 had a restrictive pattern (E/A > or = 2, n = 13). No differences were found among the groups with regard to age, gender, heart rate, and M-mode echocardiographic indices of left ventricular function. Compared with patients in group 1, those in groups 2 and 3 had more symptoms (New York Heart Association functional class III or IV) and had higher left ventricular filling pressures. The sensitivity of an E/A ratio > or = 1 for predicting a pulmonary capillary wedge pressure > or = 15 mm Hg was 75% and the specificity was 94%. Despite a similar increase of filling pressures, group 3 patients had a lower left atrial appendage emptying velocity, pulmonary venous flow reversal velocity, and mitral A velocity than did group 2 patients. The sensitivity and specificity of an E/A ratio > or = 22 for detecting left atrial dysfunction (left atrial appendage emptying velocity < or = 40 cm/sec) was 85% and 86%, respectively. In conclusion, among patients with dilated cardiomyopathy, those who had a restrictive or pseudonormal filling pattern were in a higher functional class and had higher filling pressures. Further studies are needed to determine the therapeutic and prognostic significance of left atrial dysfunction, which was common in patients with a restrictive pattern.

Adult↗

A survey of wheelchair use by paraplegic individuals in Japan. Part 1: Characteristics of wheelchair cushions.

The characteristics of wheelchair cushions used by 218 paraplegic patients who lived independent lives were surveyed to clarify the present state of wheelchair cushioning for pressure sore prevention in Japan. Out of 586 cushions surveyed, 91.0% were ready-made and the rest were custom-made. The outstanding popularity of polyurethane foam ready-made cushions (76.3%) suggested that insufficient consideration was taken in the selection of cushions. Custom-made cushions displayed unique modifications to relieve contact pressure or to stabilize sitting posture, which should be systematically provided for all patients. The variety of cushion types and the frequent dissatisfaction with cushions seen in patients with current pressure sores suggested a strong demand for the effective prescription of cushions. Furthermore, 30% of all cushions had had an excessively prolonged use, indicating insufficient follow-up. A medical system including deliberate prescription and regular follow-up of wheelchair cushions should be established for the effective prevention of pressure sores.

Adolescent↗

A survey of wheelchair use by paraplegic individuals in Japan. Part 2: Prevalence of pressure sores.

A cross-sectional survey was done to clarify the incidence of pressure sores in 218 self-supported Japanese paraplegic patients and to determine effective measures for prevention. The majority of patients (85.7%) had previous pressure sores, and 46.3% had undergone multiple surgeries. Some patients (17.9%) were still suffering from persistent sores which commonly developed at the ischial tuberosities, suggesting insufficiency of self-care practice during wheelchair activities. Sensory disturbance over the seating surface, urinary incontinence, and general complications were seen in 85.8%, 49.5%, and 18.8% of total subjects, respectively. They were seen as risk factors for pressure sores, but only urinary incontinence clearly increased the current pressure sore prevalence. Nevertheless, both self-care practice and sports activities, seen in 85.3% and 36.2% of total subjects, respectively, contributed to greatly reduce the incidence. A patient education system including acquisition of basic knowledge and proper technique should be established to promote effective prevention of pressure sores in Japan.

Adolescent↗

Unusual polyp-like structures in lobular panniculitis of a patient with Behçet's disease.

Unusual histopathologic structures were observed in lobular panniculitis of a patient with Behçet's disease. These were polyp-like in shape and protruded into cavities made of lysed fat cells. Various stages of development were observed. To determine the origin of cells making up these structures, we applied various histochemical and immunohistochemical techniques and found the cells to be histiocytes (macrophages) engaged in phagocytizing degenerated fat cells and cell membranes which had formed into membranocystic lesions.

Adipose Tissue↗

Autoregulation of portal circulation: a correlative study of circulation and vascular morphology.

To investigate the mechanism of portal circulation and the genesis of portal hypertension, an in vivo model was made to increase portal venous flow (PVF) by forming a bypass shunt between the femoral artery to the splenic venous branch in pigs and dogs via a regulatable pump. Using this model, an autoregulatory hemodynamics of the portal circulation and corresponding morphological changes of the intrahepatic vascular system were determined. Immediately after blood flow increase (100 mL/min) to the portal vein, PVF increased to the baseline level plus bypass shunt flow. But, PVF returned to the baseline level within 1 h for both animals. Portal venous resistance (PVR) at 1 h was significantly higher than the baseline level (P < 0.05). By histometric analysis of the cross-sectional area of the portal and hepatic venous branches (CSA-PV, CSA-HV) using the biopsized liver, CSA-HV at 1 h was 27.6% of the CSA-HV of the baseline level in dog, which showed narrowing and contractive changes of the hepatic venous branches, and CSA-PV at 1 h was 36.4% of the CSA-PV of the baseline level in pig, which showed narrowing and contractive changes of the portal venous branches. It is suggested that a tone of the intrahepatic vascular system has an important role in the portal autoregulatory hemodynamics.

Animals↗

Renal angiosarcoma: a case report.

We report the first case of angiosarcoma in the kidney occurring in a woman; the tumor was initially believed to be renal cell carcinoma. This malignant tumor was discovered in a patient with macrohematuria. The final diagnosis was confirmed by histologic and immunohistochemical findings. A review of the literature on this tumor is also included in the discussion.

Angiography↗

Family study of 2,8-dihydroxyadenine stone formation: report of two cases of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0).

The family members of 2 formers of 2,8-dihydroxyadenine stones were examined for history, adenine phosphoribosyltransferase (APRT) activity, genotype, urinary sediment, and urinary constituents. The patients' father showed a genotype of APRT*1/APRT*Q0, and their mother showed APRT*1/APRT*J. Patients 1 and 2 were compound heterozygotes for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0), and APRT activities were 4.5% and 4.0% of normal, respectively. 2,8-Dihydroxyadenine crystals could be seen in the urinary sediment. Treatment with allopurinol completely stopped new stone formation for 5 years in patient 1.

Adenine↗

Loss of arterial dilation in the reendothelialized area of the flow-loaded rat common carotid artery.

We have investigated regenerated endothelial cells and their possible contribution to arterial dilation in response to increased blood flow in rat common carotid artery (CCA). After endothelial denudation using a balloon catheter in the left CCA, an arteriovenous shunt was constructed between the left CCA and the left external jugular vein at 20 mm distal from the orifice in the denuded group. Animals that were given the arteriovenous shunt without denudation were used to form the nondenuded group. The blood flow rate in the left CCA was increased by sixfold after operation in the denuded group. We observed that endothelial cells were gradually regenerated from the orifice to the distal area and that the reendothelialized area after 4 to 8 weeks was approximately one third of the left CCA (5.31 +/- 1.49 mm at 4 weeks, 5.47 +/- 1.56 mm at 8 weeks). In the reendothelialized area of the left CCA after 4 to 8 weeks, the lumen diameter was significantly smaller than that of the nondenuded group and showed no significant difference from age-matched nonsurgical animals. The intimal and medial thickening, which would result in arterial stenosis in the reendothelialized area, was not observed in the denuded group, although the denuded control showed significant intimal thickening. From these results, we conclude that regenerated endothelial cells reduce intimal thickening but do not respond to increased blood flow to dilate the artery.

Angioplasty, Balloon↗