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Biomedical subjects

H Kawano

Publications and source records attributed to H Kawano.

At least 37 records · Page 2Linked to original sources

Increase in plasma levels of oxidized low-density lipoproteins in patients with coronary spastic angina.

Oxidized low-density lipoproteins (LDL) impair endothelium-dependent dilation and constrict arteries. This study examined possible relation of the circulating plasma levels of Ox-LDL to coronary spastic angina (CSA). The plasma levels of Ox-LDL were measured by ELISA in 37 consecutive patients with CSA and normal coronary angiograms and in 79 consecutive control patients. The Ox-LDL levels in patients with CSA were significantly higher than those in controls. In multivariate analysis, higher levels of Ox-LDL were a risk factor for CSA independently of other traditional risk factors. The Ox-LDL levels had a significant and positive correlation with constrictor response of coronary arteries to the intracoronary acetylcholine infusion. Thus, Ox-LDL may play a possible role in pathogenesis of coronary spasm.

Acetylcholine↗

Effect of medroxyprogesterone acetate plus estradiol on endothelium-dependent vasodilation in postmenopausal women.

The addition of medroxyprogesterone acetate (MPA) is widely accepted to remove the endometrial-cancerogenic effect of estrogen replacement therapy in postmenopausal women. To evaluate the effect of MPA on endothelial function, we measured flow-mediated vasodilation of brachial arteries after transient occlusion in a randomized, double-blind, placebo-controlled study; we concluded that the addition of MPA attenuates the favorable effects of estradiol on endothelium-dependent vasodilation.

Brachial Artery↗

Effects of combination of ACE inhibitor and angiotensin receptor blocker on cardiac remodeling, cardiac function, and survival in rat heart failure.

BACKGROUND: The mechanism and treatment of diastolic heart failure are poorly understood. We compared the effects of an ACE inhibitor, an angiotensin receptor blocker (ARB), and their combination on diastolic heart failure in Dahl salt-sensitive (DS) rats. METHODS AND RESULTS: DS rats fed an 8% NaCl diet from 7 weeks of age were treated with benazepril 10 mg/kg alone, valsartan 30 mg/kg alone, or combined benazepril and valsartan at 5 and 15 mg/kg, respectively, or at 1 and 3 mg/kg, respectively. At 16 weeks of age, DS rats exhibited prominent concentric left ventricular (LV) hypertrophy and diastolic dysfunction with preserved systolic function, as estimated by echocardiography. Despite comparable hypotensive effects among all drug treatments, the combination of benazepril 5 mg/kg and valsartan 15 mg/kg improved diastolic dysfunction and survival in DS rats more effectively than ACE inhibitor or ARB alone. Furthermore, the increase in LV endothelin-1 levels and hydroxyproline contents in DS rats was significantly suppressed only by combined benazepril and valsartan, and LV atrial natriuretic peptide mRNA upregulation in DS rats was suppressed to a greater extent by the combination therapy than monotherapy. CONCLUSIONS: The combination of ACE inhibitor and ARB, independently of the hypotensive effect, improved LV phenotypic change and increased LV endothelin-1 production and collagen accumulation, diastolic dysfunction, and survival in a rat heart failure model more effectively than either agent alone, thereby providing solid experimental evidence that the combination of these 2 agents is more beneficial than monotherapy for treatment of heart failure.

Angiotensin Receptor Antagonists↗

Cardio-aortic operation in octogenarians.

OBJECTIVE: Aging of the population is a current phenomenon in Japan, and life expectancy at 80 years old is getting longer. So we reviewed cardio-aortic operations on octogenarians at our institution. SUBJECTS AND METHODS: Thirty-three consecutive octogenarian patients who had undergone cardio-aortic operations from 1992 to 1998 were studied. There were 14 men and 19 women. The mean age was 81.9 years. Of the 33, 19 patients (58%) were in New York Heart Association class IV, and 21 patients (64%) were operated on urgently or in emergency. The procedures undergone were operation for coronary artery disease in 17 patients, operation for valvular disease in 7 patients, operation for thoracic-aorta in 7 patients, and others in 2 patients. RESULTS: The hospital mortality rate was 27% (9 patients). However, 89% of patients experiencing hospital death were in New York Heart Association class IV preoperatively and had required an emergency/urgent operation. On the other hand, there was only one hospital death (1/12, 8.3%) among the elective patients. The statistically significant risk factors for hospital death were renal insufficiency, shock, New York Heart Association class IV, intra-aortic balloon pumping, and longer cardiopulmonary bypass time. The one-, three-, and five-year-survival rate was 73%, 68%, and 55%, respectively. Of the survivors, 77% were in class I or II. CONCLUSION: Although octogenarians' hospital mortality was still very high, the mid-term results were acceptable and the survivors' quality of life was satisfactory. These data suggested that we should operate on cardio-aortic patients before they reach a very serious state, especially in octogenarians.

Age Factors↗

Integrins alphavbeta3 and alphavbeta5 mediate VSMC migration and are elevated during neointima formation in the rat aorta.

Neointima formation involves tissue expression of matrix proteins and growth factors. The role of alphavbeta3, but not alphavbeta5 integrin in vascular cells has been sufficiently investigated. The aim of the present study was to determine and compare the function of alphavbeta3 and alphavbeta5 integrins in rat aortic (RASMC) and human coronary vascular smooth muscle cells (HCSMC) and to characterize their expression accompanying neointima formation in vivo. RASMC and HCSMC express alphavbeta3 and alphavbeta5 integrin subunits. The alphavbeta5 integrin predominantly mediated adhesion of RASMCs to vitronectin and spreading on vitronectin via RGD-binding sequences. In contrast, the alphavbeta3 integrin did not contribute to the adhesion and spreading on fibronectin, vitronectin, gelatin or collagen I coated layers. PDGF-directed migration through gelatin coated membranes involved both alphavbeta3 and alphavbeta5 integrins. Selective blocking antibodies for alphavbeta3 and alphavbeta5 inhibited migration of RASMC and HCSMC by more than 60 % (p < 0.01). Integrin expression was studied in vivo in thoracic aorta of Sprague Dawley rats before and after balloon injury. In situ hybridization demonstrated low signals for alphav, beta3 and beta5 mRNA in uninjured aorta, which increased significantly at 14 days, localized predominantly in the neointima. Northern analysis of aorta after 14 days of injury also demonstrated an upregulation of alphav, beta3 and beta5 mRNA compared to uninjured aorta. Consistent with the increase in message levels, increased integrin protein expression was seen in the neointima after 7 and 14 days. This study provides evidence that alphavbeta3 and alphavbeta5 are elevated during neointima formation in the rat and indicates a novel role for alphavbeta5 participating in mechanisms regulating smooth muscle cell migration.

Animals↗

Serum acid phosphatase as a tumour marker in giant cell tumour of bone.

The serum acid phosphatase value was examined in nine patients with giant cell tumour of bone. Five showed a high level of acid phosphatase, which fell to within normal limits after surgery. Although the remaining four patients showed a normal acid phosphatase level before surgery, the postoperative acid phosphatase level was lower than the preoperative level in each case. Therefore, it is strongly suggested that serum acid phosphatase is a useful tumour marker in diagnosing giant cell tumour of bone as well as in evaluating the efficacy of treatment.

Acid Phosphatase↗

Soft-tissue haemangioma and periosteal new bone formation on the neighbouring bone.

Deeply situated soft-tissue haemangioma sometimes causes periosteal new bone formation on the neighbouring bone. The purpose of this study was to elucidate the aetiological factors for this phenomenon. We studied 25 patients with soft-tissue haemangioma on whom plain radiographs and computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations were performed. We examined the presence or absence of periosteal new bone formation, haemangioma-bone distance, size of haemangioma and pain. Periosteal new bone formation was seen in 12 of 25 patients. In these 12 patients, the haemangioma was adjacent to the bone in 11 patients, while the haemangioma-bone distance was 4 mm in the other patient. In the remaining 13 patients who had no periosteal new bone formation, the haemangioma-bone distance was 5-27 mm. Pain in the former group was stronger than that in the latter group, the difference being statistically significant. There was no statistically significant difference in size of haemangioma between the two groups. Therefore, the main factor that induces periosteal new bone formation on the neighbouring bone was not the size of haemangioma, but the distance between the haemangioma and the bone.

Adolescent↗

Osteofibrous dysplasia of the ulna.

We experienced two patients with osteofibrous dysplasia of the ulna. Both of them showed typical radiographic findings of osteofibrous dysplasia, except for location. One patient underwent surgery at the age of 15 years to confirm the diagnosis histologically. Although the tumor recurred 5 months after the surgery, expansion of the lesion seemed to cease at the age of 25 years. In the other patient, the natural course was observed. The tumor showed a tendency toward spontaneous regression at the age of 11 years. Therefore, the nature of osteofibrous dysplasia in the ulna seems to be the same as that in the tibia and fibula. Surgery must be delayed for as long as possible in osteofibrous dysplasia of the ulna, as well as that of the tibia and fibula.

Adolescent↗

Resorption of synthetic porous hydroxyapatite and replacement by newly formed bone.

Synthetic porous hydroxyapatite (HA) is commonly used as a bone substitute for bone defects which, previously, would have been treated by autogenous bone grafting. HA has been thought to be a nonbiodegradable material that remains as it is implanted. However, after long-term follow-up, some authors report that the margin of implanted HA blocks or granules is absorbed, suggesting that HA is biodegradable. We experienced a patient in whom synthetic HA blocks implanted in a bone defect of the ilium after the harvesting of full-thickness bone for grafting were extensively absorbed and replaced by newly formed bone 6 years and 7 months after the implantation. Therefore, we conclude that HA is biodegradable. Sintering temperature, porosity, and pore diameter seem to influence the biodegradability of HA.

Absorption↗

Dopamine and serotonin uptake inhibitors on the release of dopamine and serotonin in the nucleus accumbens of young and aged rats.

Nucleus accumbens (ACC) of young (4 months old) and aged (24 months old) Wistar rats were perfused with dopamine (DA) uptake blocker, cocaine, or the serotonin (5-HT) selective reuptake inhibitor, fluoxetine, through the microdialysis probe membrane, used to assess the dopamine transporter (DAT) or serotonin transporter (SERT) modulation. The basal extracellular DA release in the ACC was significantly lower in aged rats than young rats. Analysis of DA and 5-HT concentrations in the ACC with increased positive GFAP revealed that DA and DOPAC levels of aged rats were decreased to 55 and 60% of those in young rats, respectively. After co-perfusion with cocaine, both DA and 5-HT releases in the ACC were increased in the young and aged groups. However, the magnitude of the increased DA release was lower in aged rats than young rats. Co-perfusion with fluoxetine showed lower magnitude of the increased DA release in aged rats. It appears that the DAT and SERT system responds initially to ACC cell loss with age, and that especially ACC DAT in the aged rat is more degenerative compared with the young rats. These findings suggest that the serotonergic system with SERT in the remaining ACC neurons show an early adaptive response and resistance to the normal aging and maintain the multiple regulatory system in the ACC despite neural loss since the dopaminergic neurons in the aged animals are vulnerable to aging.

Aging↗

Risk stratification analysis of operative mortality in heart and thoracic aorta surgery: comparison between Parsonnet and EuroSCORE additive model.

OBJECTIVE: Our purpose was to compare the performance of risk stratification model between Parsonnet and European System for Cardiac Operative Risk Evaluation (EuroSCORE) in our patient database. METHODS: From August 1994 to December 2000, 803 consecutive patients have undergone heart and thoracic aorta surgery using cardiopulmonary bypass and scored according to Parsonnet and EuroSCORE algorithm. The population was divided into five clinically relevant risk categories. We compared correlation of predicted mortality and observed mortality between these two models. Score validity was assessed by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: Overall hospital mortality was 4.5%. In Parsonnet model, predicted mortality was 2.4% for 0-4% risk, 6.7% for 5-9% risk, 12% for 10-14% risk, 17% for 15-19% risk, 25% for 20% plus risk, and 10.4% for overall patients. Observed mortality was 2.4, 0.4, 5.9, 8.7, 11, and 4.5%, respectively. The thoracic aorta and valve cohort indicated poor correlation between predicted and observed mortality compared to coronary cohort. In the EuroSCORE model, predicted mortality was 1.4% for 0-2% risk, 4.0% for 3-5% risk, 6.7% for 6-8% risk, 9.7% for 9-11% risk, 13% for 12% plus risk, and 5.3% for overall patients. Actual mortality was 0, 1.5, 6.8, 11, 21, and 4.5%, respectively. Each of the thoracic aorta, valve, and coronary cohort indicated good correlation between predicted and observed mortality. Areas under the ROC curves were 0.72 in Parsonnet and 0.82 in EuroSCORE. CONCLUSIONS: The EuroSCORE additive model yielded good predictive value for hospital mortality of Japanese patients undergoing not only cardiac but also thoracic aortic surgery.

Algorithms↗

SADS: A new component of Fas-DISC is the accelerator for cell death signaling and is downregulated in patients with colon carcinoma.

Fas is the death receptor, transducing cell death signaling upon stimulation by Fas ligand. During Fas-initiated cell death signaling, the formation of Fas-death inducing signaling complex (Fas-DISC) is the first step. Here we have identified a new component of Fas-DISC which we call 'small-accelerator for death signaling' (SADS). SADS cDNA encodes a 150 amino acid polypeptide (Mr = 16,700). During Fas-mediated cell death, SADS enhances the interaction of Fas-death domain-interactive factors (FADD) and procaspase-8, and deletion mutant analysis has identified FADD- and caspase-8-interactive domains in SADS. Inhibition or removal of SADS delays Fas-mediated cell death. In addition, we demonstrate the deletion or mutation of SADS in patients with colon carcinoma and that exogenous SADS expression in human colon carcinoma SW480 cells that lack SADS leads to re-acquisition of Fas-mediated cell death. Here, we propose that SADS is one of the cell death-associated factors and enhances Fas-DISC formation, especially FADD and procaspase-8 recruitment.

Apoptosis↗

Immunohistochemical localization of calbindin D-28k in the migratory pathway from the rat olfactory placode.

The spatiotemporal localization of calbindin D-28k (Calb), a calcium-binding protein, was examined immunohistochemically in the developing rat olfactory system with special reference to cell migration from the olfactory placode. Calb immunoreactivity was first detected at embryonic day 12 (E12) in a few cells just outside the olfactory epithelium, and at E13, Calb-immunoreactive cells were found scattered in the laminin-rich mesenchyme. By E14, Calb-immunoreactive cells had increased in number and were seen along the entire migratory route between the vomeronasal organ, a derivative of the medial olfactory pit, and the ventromedial surface of the telencephalic vesicle. Calb neurones were not seen in the olfactory epithelium, a derivative of the lateral olfactory pit. Although the distribution pattern of Calb-immunoreactive cells was similar to that of luteinizing hormone releasing hormone (LHRH)-producing neurones, which are known to originate in the vomeronasal organ and migrate into the forebrain, Calb and LHRH immunoreactivities were contained in separate neuronal populations. Calb-immunoreactive cells were localized along the vomeronasal nerves, identified by labelling the vomeronasal organ with the lipophilic dye, DiI, and strongly immunoreactive for neural cell adhesion molecule (NCAM). These data strongly suggest that, in addition to LHRH neurones, the rat vomeronasal organ generates Calb-immunoreactive neurones which migrate along the vomeronasal nerves to enter the forebrain. The final fate and functional importance of these cells remains to be determined.

Animals↗

Useful polyclonal antibodies against synthetic peptides corresponding to immunoglobulin light chain constant region for immunohistochemical detection of immunoglobulin light chain amyloidosis.

For the immunohistochemical detection of immunoglobulin (Ig) light chain amyloidosis on formalin-fixed, paraffin-embedded tissue sections, we prepared polyclonal antibodies against synthetic peptides corresponding to positions 118-134 of Ig lambda light chain and positions 116-133 of Ig kappa light chain. Nineteen cases of systemic Ig lambda light chain amyloidosis (Alambda amyloidosis), 10 cases of systemic Ig kappa light chain amyloidosis (Akappa amyloidosis), one case of immunohistochemically unclassified systemic amyloidosis and five cases of localized Alambda amyloidosis were tested with these antibodies. Anti-lambda (118-134) antiserum and the affinity-purified antibody both reacted with 18 of the 19 cases of systemic Alambda amyloidosis and all cases of localized Alambda amyloidosis, although the immunoexpression was somewhat variable in intensity in different areas within the same specimen in both systemic and localized amyloidosis. The signal intensities in plasma cells and serum reacted for anti-lambda (118-134) antiserum were weaker than signals obtained with commercially available anti-Ig lambda light chain antibodies. Anti-kappa (116-133) antiserum and the affinity-purified antibody reacted with nine of the 10 cases of systemic Akappa amyloidosis. We conclude that these antibodies against synthetic peptides corresponding to the Ig light chain constant region are useful for the classification of amyloidosis on formalin-fixed, paraffin-embedded tissue sections.

Amyloidosis↗

Vascular amyloid of unknown origin and senile transthyretin amyloid in the lung and gastrointestinal tract of old age: histological and immunohistochemical studies.

The histological and immunohistochemical characteristics and the incidence of amyloid deposits in the tissues of the lung and gastrointestinal tract were investigated in 64 autopsied individuals who were 80 years and older (age range: 80-92 years; mean: 83.3 years). Immunohistochemical examination was performed with antibodies against amyloid A, transthyretin, immunoglobulin lambda and kappa light chain amyloid fibril proteins, beta2-microglobulin, beta protein, apolipoprotein AI, apolipoprotein AII, atrial natriuretic peptide, apolipoprotein E, and amyloid P component. Transthyretin amyloid fibril protein (ATTR) deposits were observed in five cases (7.8%). Gastrointestinal amyloid deposits of unknown origin were observed in the veins of the gastrointestinal tract in 26 cases (40.6%). This amyloid was regarded as portal amyloid with respect to distribution pattern. Pulmonary vascular amyloid deposits of unknown origin were observed in 12 cases (18.8%). These amyloid deposits were found mainly in medium-sized veins in the lungs and did not react with any antibodies against amyloid fibril proteins except apolipoprotein E and amyloid P component. Eleven of the 26 cases (42.3%) showing portal amyloid also showed pulmonary vascular amyloid of unknown origin. The pulmonary vascular amyloid deposits were similar to the portal amyloid deposits with respect to their morphological features and their relation to elastic fibers in the vessels. Further morphological investigation and biochemical analysis of the pulmonary vascular amyloid and portal amyloid will resolve questions of their origins and relation.

Aged↗

Identification of a landmark in a roentgenographic cephalogram by employing the wavelet neurons.

This paper describes an identification method of a landmark in a roentgenographic cephalogram by employing the input-correlated wavelet neurons. For the purpose of improvement of identification precision, a novel pattern matching method, named "wavelet neuron matching (WNM)," is proposed in this paper. Furthermore, the "weighted window", which is proposed in this paper, enables us to consider the orthodontists' knowledge on local information as precisely as possible. The effectiveness and the validity of the proposed method have been verified by the experiments to identify a landmark called Menton.

Cephalometry↗

Glutathione attenuates coronary constriction to acetylcholine in patients with coronary spastic angina.

This study examined the effect of reduced glutathione (GSH), an important antioxidant that restores intracellular redox imbalance and prevents inactivation of endothelial-derived nitric oxide, on the abnormal vasomotor reactivity in spastic coronary arteries. The responses of epicardial diameter of the left coronary arteries to intracoronary infusion of acetylcholine (ACh; 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of GSH (50 mg/min for 6 min) or saline as a placebo in 24 patients with coronary spastic angina and in 28 control patients. All of the spastic coronary arteries showed constrictor response to ACh, whereas the control coronary arteries as a whole showed only minimal diameter changes to ACh. GSH infusion suppressed constrictor response of epicardial diameter to ACh in patients with coronary spastic angina, whereas it had no significant effect in control subjects. Saline infusion did not have any effects. The results indicate that GSH attenuated the constrictor response to ACh in epicardial coronary arteries of patients with coronary spastic angina. GSH may have an important role in the regulation of coronary vasomotor function in patients with coronary spastic angina.

Acetylcholine↗