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Biomedical subjects

K Kawamura

Publications and source records attributed to K Kawamura.

At least 163 records · Page 9Linked to original sources

Serine protease inhibitors expressed in the process of budding of tunicates as revealed by EST analysis.

To identify genes expressed during budding of the tunicate Polyandrocarpa misakiensis, we isolated and sequenced 624 clones from a directionally constructed cDNA library to prepare a catalog of expressed sequence tags (ESTs). A total of 233 ESTs matched genes of known sequence in the SwissProt database. About 24% out of them showed high similarity to ribosomal proteins, twice the value (12%) of pre-budding animals. ESTs involved in the respiratory chain also appeared with significant redundancy, suggesting that tunicate budding is accompanied by the enhancement of energy conversion as well as protein synthesis. Serine protease inhibitor (serpin) afforded another striking example of a gene that was highly expressed in the process of budding. The deduced amino acid sequences of five serpin cDNAs all had two consensus signatures of the Kazal's type of secretory protease inhibitor, one of which had an active site for trypsin and the other for elastase. In line with this, recombinant GST-fusion protein showed both trypsin and elastase inhibitor activities. In accordance with the EST analysis, the hemolymph taken from the budding stage showed the highest activity of trypsin inhibitor. We discuss a possible role that Polyandrocarpa serpins may play in bud development by counteracting trypsin-like serine protease, which could facilitate dedifferentiation of formative tissues.

Amino Acid Sequence↗

Cartilaginous membranocystic lesions mimicking membranous lipodystrophy of bone.

Two cases are presented in which membranocystic lesions were observed in the cartilaginous tissue of surgical specimens. In both cases, the histological and ultrastructural features were reviewed, and S-100 protein distribution was examined immunohistochemically in one case. In both cases, the membranocystic lesions were observed to be adjacent to ballooned chondrocytes. In one case, several chondrocytes showed partially membranocystic lesions in their cytoplasm. The chondrocytes and nuclei in membranocystic lesions were stained positively for S-100 protein. It is suggested that the membranocystic lesions in the cartilaginous tissue were associated with the degeneration of the chondrocytes.

Adolescent↗

Discovery of a structurally novel opioid kappa-agonist derived from 4,5-epoxymorphinan.

A new type of kappa-agonist, 17-cyclopropylmethyl-3, 14 beta-dihydroxy-4,5 alpha-epoxy-6 beta-[N-methyl-trans-3-(3-furyl) acrylamido]morphinan hydrochloride (1, TRK-820), was discovered by a new working hypothesis. The "message-address concept" for opioid antagonists and the "accessory site" for general antagonists were applied to design TRK-820. A unique structural feature of TRK-820, which is different from other prototypical kappa-opioid receptor agonists, is the existence of the 4,5-epoxymorphinan structure with a tyrosine-glysine moiety for endogenous opioid peptides such as dynorphins. TRK-820 exhibited high potency and high kappa-selectivity in guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. In the mouse acetic-acid-induced writhing model and mouse tail flick model of antinociception, TRK-820 was 85-140 times more potent than morphine and 85-350 times more potent than U-50488H. This structurally novel kappa-agonist showed neither aversion nor preference in the Conditioned Place Preference test, in spite of the fact that prototypes of kappa-agonists (U-50488H derivatives) demonstrated aversion.

Animals↗

Hepatitis C virus infection and heart diseases: a multicenter study in Japan.

As a collaborative research project of the Committees for the Study of Idiopathic Cardiomyopathy, a questionnaire was sent out to 19 medical institutions in Japan in order to examine the possible association between hepatitis C virus (HCV) infection and cardiomyopathies. Hepatitis C virus antibody was found in 74 of 697 patients (10.6%) with hypertrophic cardiomyopathy (mean age, 57.7 years) and in 42 of 663 patients (6.3%) with dilated cardiomyopathy (mean age, 56.5 years); these prevalences were significantly higher than that found in volunteer blood donors in Japan (2.4%, 50-59 years of age, each p<0.0001). The prevalence was significantly higher in patients suffering from hypertrophic cardiomyopathy as opposed to those with dilated cardiomyopathy (p<0.01). The presence of HCV antibody was detected in 650 of 11,967 patients (5.4%) patients seeking care in 5 academic hospitals. Various cardiac abnormalities were found among these patients, arrhythmias being the most frequent. These observations suggest that HCV infection is an important cause of a variety of otherwise unexplained heart diseases.

Cardiomyopathies↗

CD36 abnormality and impaired myocardial long-chain fatty acid uptake in patients with hypertrophic cardiomyopathy.

Some patients with hypertrophic cardiomyopathy (HCM) demonstrate abnormal myocardial long-chain fatty acid (LCFA) metabolism. However, the exact mechanism involved is unknown. Recently, it was proposed that myocardial cells take up LCFAs via a specific mechanism, in which the CD36 molecule has been implicated as a possible candidate molecule. In addition, a high prevalence of CD36 deficiency was also found in a small number of HCM patients. Accordingly, the investigation of abnormality of the CD36 molecule in a large number of HCM patients may be useful in finding the possible cause of HCM. Moreover, the analysis of myocardial LCFA uptake in patients with molecular abnormalities may be helpful in understanding the possible function of this molecule. In this study, in order to discover the relationship between HCM and the CD36 molecular abnormality, the expression level of platelet CD36 and CD36 cDNA in 55 HCM patients was analyzed. Twelve patients showed negligible (<5%) CD36 expression on their platelets. Among them, one was found to be homozygous for the C-478-->T substitution and 6 were heterozygous for the C-478-->T substitution. In 9 patients, CD36 was expressed by less than 50% of the platelets. One of them was found to be heterozygous for the C-478-->T substitution. Two other patients were also found to be heterozygous for this point mutation, although their platelets expressed CD36. Thus, 23 out of 55 (41.8%) HCM patients had negligible (<5%) or reduced (<50%) levels of CD36 expression on platelets, or had a point mutation of CD36 cDNA. These 55 HCM patients were also evaluated with myocardial scintigraphy both for LCFA uptake and perfusion, which showed a moderate to severe discrepancy between myocardial LCFA accumulation and myocardial perfusion in 95.5% of the patients (21/23). On the other hand, 70% of the patients with normal (>90%) CD36 expression (14/20) did not show any severe discrepancies between myocardial LCFA accumulation and myocardial perfusion. These data could suggest that abnormal myocardial LCFA metabolism seen in HCM patients may be related to abnormality of the CD36 molecule, and that abnormalities of this molecule may be linked to the cause of some types of HCM.

Adult↗

Detection of myocardial ischemia with a computer-assisted 12-lead 24-hour ECG monitoring system (EAGLE) in patients with suspected unstable angina.

This study was undertaken to evaluate the diagnostic value of a new device, the 'EAGLE' computer-assisted multiple-lead long-term electrocardiography (ECG) monitoring and analyzing system, in patients with suspected unstable angina, and to compare the results with the Holter monitor. A total of 101 patients with a history of suspected unstable angina underwent a simultaneous 24-h examination with the EAGLE and 2-channel Holter monitors. The diagnosis of unstable angina was established in 70 patients: 41 had significant organic stenosis, and 29 had coronary spasm. Ischemic ST deviations were detected 229 times in 44 patients (62.9%) with the EAGLE system and 101 times in 20 patients (28.6%) with the Holter monitor. The sensitivity of myocardial ischemia in unstable angina with the EAGLE system was significantly higher than that with Holter monitor (62.9 vs 28.6%, p<0.05). The difference of sensitivity was due mainly to the low detection rate of the Holter monitor for asymptomatic myocardial ischemia (EAGLE vs Holter; 187 times vs 72 times) and myocardial ischemia in the infero-posterior area in patients with organic stenosis (30 times vs none). It is concluded that the EAGLE system is a sensitive tool for the diagnosis of unstable angina in patients without significant ECG changes, and an excellent tool for evaluating silent myocardial ischemia or myocardial ischemia of the infero-posterior area.

Angina, Unstable↗

Prosthetic ball valve endocarditis due to Gemella species.

A case is presented of endocarditis that was affecting a prosthetic ball valve (Starr-Edwards) and which was caused by Gemella species. A 57-year-old man was admitted with a 3-day history of abdominal pain with fever. At the time of admission, his temperature was 37.7 degrees C and laboratory tests showed elevated inflammatory parameters and an increased neutrophil count. However, transthoracic echocardiogram showed no vegetation. During hospitalization, Gemella spp. were detected by blood culture, and a transesophageal echocardiogram showed vegetation on the prosthetic valve. He was treated with intravenous ampicillin and astromycin, and also underwent valve replacement. This is the first case in Japan of infective endocarditis of a prosthetic valve due to Gemella spp.

Endocarditis, Bacterial↗

Effect of beta-blocker treatment in dilated cardiomyopathy with bradyarrhythmias.

This study was performed to evaluate whether beta-blocker therapy was effective in patients with nonischemic dilated cardiomyopathy (DCM) and bradyarrhythmias supported by pacemaker implantation. Beta-blocker therapy is useful for some patients with DCM, especially those with rapid heart rate or residual nonfibrotic myocardium in the left ventricle, but no data exist on whether beta-blocker therapy is useful in patients with DCM and bradyarrhythmias. The effectiveness of beta-blocker therapy was prospectively evaluated in patients with DCM and bradyarrhythmias supported by pacemaker implantation and compared with those without these arrhythmias. Beta-blocker therapy was started in 63 patients (45 men, 18 women, aged 11-83 years) with DCM, in whom 7 had bradyarrhythmias and 56 did not. These bradyarrhythmias were atrioventricular block, sick sinus syndrome and atrial fibrillation with slow heart rate. Of the 56 patients without bradyarrhythmias, 42 (75%) (group 1) responded to beta-blocker therapy, but 5 of the 7 with bradyarrhythmias (71%) (group 2) also responded. Left ventricular end-diastolic dimension was reduced (6.5 +/- 0.6 cm to 5.6 +/- 0.5 cm; p < 0.0001 in group 1; 6.6 +/- 0.8 cm to 5.5 +/- 0.2 cm; p < 0.02 in group 2) and left ventricular fractional shortening was improved (13 +/- 4% to 27 +/- 7%; p < 0.0001 in group 1; 12 +/- 4% to 29 +/- 10%; p < 0.05, in group 2) to the same degree in both groups. These results indicate that beta-blocker therapy for DCM is effective not only in patients without bradyarrhythmias but also in those with bradyarrhythmias supported with pacemaker implantation.

Adolescent↗

Solitary papillary muscle hypertrophy as a possible form of hypertrophic cardiomyopathy.

Patients can present with hypertrophied papillary muscles in the left ventricle, even without hypertrophy in other segments, and they have electrocardiographic (ECG) abnormalities suggestive of hypertrophic cardiomyopathy (HCM). This study was performed to evaluate whether the solitary papillary muscle hypertrophy was related to HCM. By analyzing 6731 echocardiographic studies between 1990 and 1994, the incidence of patients with papillary muscle hypertrophy was retrospectively examined, as well as the ECG features and family history related to HCM in these patients. After the normal size of the anterolateral and posteromedial papillary muscles was obtained from echocardiographic studies in 40 healthy subjects (0.7 +/- 0.2 cm for each of the vertical and horizontal axis), papillary muscle hypertrophy was defined as follows: either the vertical or horizontal diameter of at least one of the 2 papillary muscles was more than 1.1 cm (mean+2SD in the normal subjects). Using this definition, 29 patients with papillary muscle hypertrophy were identified, of whom 14 (48%) showed high voltage QRS complexes, 10 (34%) showed T wave inversion, and 6 (21%) showed abnormal Q waves. Ten patients (34%) had a family history of HCM. In 2 patients that were followed for 18 and 11 years, respectively, the voltages of the QRS complexes and inverted T waves progressed with the hypertrophy of the papillary muscle. These findings suggest that solitary papillary muscle hypertrophy is related to HCM and that papillary muscle hypertrophy is a newly identified subtype of or an early form of HCM.

Adolescent↗

A case of malignant lymphoma with diastolic heart failure.

In patients with malignant lymphoma, the first signs and symptoms are frequently noncardiac and clinical manifestations of cardiac involvement are often nonspecific. This case report presents a patient with malignant lymphoma whose first manifestation was characteristic of heart failure, mainly due to diastolic dysfunction, and whose postmortem examination revealed massive myocardial invasion.

Child, Preschool↗

Morphogenesis of the hypothalamus and hypophysis: their association, dissociation and reassociation before and after "Rathke".

Recent progress in the experimental morphology of the development of amphibian pituitary gland is reviewed. A series of transplantation experiments were carried out using wild-type embryos of the toad as a donor and albino embryos as a recipient. Melanin granules in the wild-type cells allowed tracing of the developmental fate of the grafts as a visible cell marker. These studies have demonstrated that the pituitary gland is not a stomodeal derivative, as it has long been believed to be under the name of "Rathke's pouch". The adenohypophysis is of neural origin. The anterior part of the neural ridge (ANR) in the neuroectoderm of the open neurula gives rise to the whole adenohypophysis, i. e., pars distatis, pars intermedia and pars tuberalis. The presumptive hypothalamus is apposed caudally to the pituitary primordium. A part of the ANR contributes neurons to the preoptic hypothalamus even after closure of the neural tube. The anlagen of the olfactory system, which include the nasal epithelia and the olfactory bulbs, are situated on both sides of the pituitary primordium in the neural ridge. In both hypothalamic-hypophyseal and olfactory systems, the peripheral and central parts derive from closely affiliated cell populations, suggesting their clonal relationships. Development of the hypophysis and hypothalamus is interdependent. On one hand, a connection with the embryonic hypothalamus is essential for the pituitary proopiomelanocortin cells to develop. On the other hand, neither the hypothalamic median eminence nor its axonal supply develops without the presence of the pituitary primordium. Novel aspects of the ontogeny and phylogeny of these organs are discussed with special reference to the role of the neural ridge in the generation of a spectrum of chemoreceptive organs.

Animals↗

Antitumor vaccine effect of irradiated murine neuroblastoma cells producing interleukin-2 or granulocyte macrophage-colony stimulating factor.

We have examined vaccination effects of cytokine-producing murine neuroblastoma cells (C1300). C1300 cells retrovirally transduced with interleukin-2 (IL-2) or granulocyte macrophage-colony stimulation factor (GM-CSF) gene were established. Their in vitro proliferation rates and the class I expression of major histocompatibility complex were not different from those of wild-type cells. Five-Gy irradiation of the respective cytokine producers slightly reduced the in vitro cell growth but treatment with 15 Gy significantly impaired the proliferation. In contrast, the secretion of both cytokines from the respective transduced cells was retained compared with the cell growth. We immunized syngeneic mice with irradiated wild-type cells as a control or cytokine-producing cells and challenged the mice with unirradiated wild-type cells. The control mice developed tumors of the challenged wild-type cells, on the contrary, the mice which had received irradiated IL-2 or GM-CSF producers did not. Thus, IL-2- or GM-CSF-expressing syngeneic tumor cells can be potentially used as a tumor vaccine by inducing protective immunity against low immunogenic neuroblastomas in the inoculated hosts.

Animals↗

[Factors influencing admission to nursing homes among frail and bedridden elderly persons receiving public health and welfare services].

A prospective study was conducted to elucidate the factors influencing admission to nursing homes among frail and bedridden elderly persons. The subjects were 149 persons, 70 years of age and above, who were living in Goshiki-cho, Hyogo prefecture and were receiving services from public health and welfare organizations. All of the subjects had a family physician and their own residence or own room at home. A follow-up study of admissions to nursing homes was performed from 1991 to 1996. The main results were as follows: 1. During the study (about 5 years), 42.9% (N = 64) of subjects were staying at home, 38.9% (N = 58) died at home, and 16.8% (N = 25) were admitted to nursing homes. 2. To find factors influencing admission to nursing homes, an analysis using Cox proportional, hazard model was conducted. Major factors found were high age, women, disabilities of hearing and eyesight, and difficulty in communication. The admission rate to nursing homes was especially high among patients 90 years of age or greater. 3. The admission rate to nursing homes was higher in subjects receiving home help services compared to the rest of the group. 4. Remarkable differences in household composition were observed between those who continued to stay at home and those admitted to nursing homes. Among the subjects living alone or living with a spouse, the mean age was significantly higher in the group who were admitted to nursing homes than those staying at home. In the case of two or three-generation households, the admission rate to nursing homes was high when the household lacked caregivers.

Aged↗

[Enhanced MR imaging with a nonionic contrast gadolinium complex, Gadoteridol, for lumbar disc herniation].

The aim of this study was to evaluate the usefulness for lumbar disc herniation of enhanced imaging with a nonionic contrast gadolinium complex (Gadoteridol). Among 130 discs in 26 patients, 27 herniated discs were shown on MR sagittal imaging. They were classified into 4 types according to the enhancement pattern of the disc on MR sagittal imaging (Type Ia: nonenhancement, Type Ib: globular enhancement, Type II: strong enhancement, Type III: ring enhancement). The results were as follows: Type Ia: 3, Type Ib: 15, Type II: 7, Type III: 2. A total of herniated discs were enhanced with Gadoteridol. Surgery was performed in 5 patients (Type Ib: 1, Type II: 4). The herniated disc of Type Ib extruded but did not rupture the posterior ligament, whereas the herniated discs of Type II extruded and ruptured the posterior ligament. Thus, the herniated discs were enhanced with the nonionic contrast agent Gadoteridol. If the disc herniates over the posterior ligament, it might be strongly enhanced. Therefore, enhanced MR imaging is thought to be useful to establish the diagnosis of lumbar disc herniation.

Adult↗

[Studies on the influence of riboflavin intake to osteogenesis in rats].

Influence of an intake of the riboflavin that exerts upon osteogenesis in this research, was examined by a nutritional methods. It search the condition of femur in rats they reared and given three type riboflavin dosage, namely, sufficient riboflavin, few deficient riboflavin and administered sufficient after few deficient riboflavin. As a result, an influence of riboflavin dosage was not recognized about each of the body weight, food intake, and weight and length of femur. In other words, a deficiency symptom was not observed seemingly in the rat that given riboflavin deficiency diet. Also, the calcium contents in the femur decreased significantly by the deficiency of riboflavin. And, the low value was shown the even in the rat that administered sufficient fibroflavin later. Furthermore, even breaking force of the femur decreased by the deficiency of riboflavin.

Animals↗

Localization of extracellular matrix molecules, integrins and their regulators, TGF betas, is correlated with axon pathfinding in the spinal cord of normal and Danforth's short tail mice.

To clarify the roles of extracellular matrix molecules (ECMs) and their receptors, integrins, in axonal pathfinding, their spatiotemporal localization was studied immunohistochemically in the developing mouse spinal cord. Immunoreactivities for collagen type IV (Col IV), laminin, integrins (alpha2, alpha3 and beta1 subunits), and transforming growth factor (TGF) betas (TGF beta2 and TGF beta3), putative regulators of gene expression of these molecules, were localized on the midline of the ventral spinal cord, or the 'floor plate', in normal ICR mice. These immunoreactions appeared at embryonic day 9 (E9), when commissural axons began to cross the floor plate, and peaked at E13-E14 when more axons crossed, turned rostrally, and projected longitudinally. At this stage, TAG-1-immunopositive commissural axons passed through the floor plate region. Longitudinal axons, on the other hand, projected ipsilaterally parallel to the midline. Immunoreactions for ECMs, integrins and TGF betas were weakly positive at the midline until postnatal day 0 (P0), after which they decreased markedly. In Danforth's short tail (Sd) heterozygous mutants with discontinuous floor plates, immunoreactions for ECMs, integrins, and TGF betas were not detected at P0. Few crossing axons were seen at this stage, and longitudinally ascending axons crossed via aberrant paths in these regions. These results suggest that the restricted localization of ECMs, integrins, and TGF betas at the floor plate is involved in the pathfinding of commissural and longitudinal axons.

Animals↗