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Biomedical subjects

T Kuribayashi

Publications and source records attributed to T Kuribayashi.

At least 55 records · Page 3Linked to original sources

The beta-adrenergic receptor/adenylate cyclase system in the cardiac ventricles of a hypertrophic cardiomyopathy rat model.

The WKY/NCrj rat strain is considered to be a good animal model for hypertrophic cardiomyopathy (HCM). The purpose of this study was to examine the beta-adrenergic receptor/adenylate cyclase system in the cardiac ventricles of these rats. beta-adrenergic receptor density (Bmax) in the right ventricle (RV) was higher in WKY/NCrj than in Wistar rats. In contrast, Bmax in the interventricular septum (IVS) was lower in WKY/NCrj than in Wistar rats. Isoproterenol-stimulated adenylate cyclase activity in cardiac ventricular slices showed that changes corresponded to the changes of Bmax in every type of studied cardiac ventricle. The intracellular adenylate cyclase pathway (GTP gamma S-, NaF- and forskolin-stimulated adenylate cyclase activity in cardiac ventricular particulate fraction) did not differ between WKY/NCrj and Wistar rats in any region of the cardiac ventricles. Catecholamine levels tended to be low in the RV and to increase in the IVS of WKY/NCrj rats. Our results suggest that the activity of the beta-adrenergic receptor/adenylate cyclase system varies in different cardiac ventricles of the WKY/NCrj rat model for HCM.

Adenylyl Cyclases↗

Echo/Doppler diagnosis of tetralogy of Fallot, ventricular septal defect, pulmonary valve dysplasia, and hypertrophic cardiomyopathy in WKY/NCrj rats.

We examined the hearts of 97 WKY/NCrj rats, a strain which spontaneously develops congenital cardiac malformations, by means of echocardiography with a pulsed Doppler ultrasound, and compared the results with those of 20 WKY/Ta rats and 30 normal Wistar rats. Dissection of these WKY/NCrj rats revealed a ventricular septal defect (VSD) in 20 and pulmonary valve dysplasia (PVD) in 41, both VSD and PVD occurring together in 18. VSD was readily diagnosed in vivo by the jet flow signal derived from the left-to-right shunt near the membranous portion, with a sensitivity of 85% and a specificity of 99%. Ultrasound imaging revealed overriding of the aorta and right ventricular (RV) hypertrophy in 18 of the 20 rats with VSD. Of the 20 rats with VSD, 10 had a systolic high-velocity jet across the RV outflow indicating an infundibular stenosis. PVD was commonly accompanied by a pulmonary regurgitation signal, with severe cases showing intensified echo and low excursion of the cusps. The regurgitation signal showed a good diagnostic value for PVD with a sensitivity of 82% and a specificity of 85%. In the remaining 54 WKY/NCrj rats without VSD or PVD, the ratio of mean left ventricular (LV) wall thickness to cavity dimension, the fractional shortening of the LV dimension, and the septal to LV free wall thickness ratio were all abnormally high, and the motion of the ventricular septum was reduced in most of the cases compared with that of the other two strains. All these features resemble the hypertrophic cardiomyopathy seen in humans, which further promises that the rats should be a useful model for the controversial disease.

Animals↗

Primary non-AIDS related brain lymphoma. Patterns of failure following radiotherapy.

Thirteen patients with primary brain lymphoma (PBL) were treated with radiotherapy. Three patients also had ocular involvement with retinal masses at initial presentation. All but one patient received conventional whole brain irradiation and, in addition, spinal irradiation, intrathecal methotrexate or orbital irradiation were given in two, two and four patients respectively. The radiation doses for involved sites ranged from 40 to 65 Gy, and for prophylactic sites from 30 to 50 Gy. After radiotherapy, all patients had complete regression of the tumor on computed tomography. Nine patients relapsed, 5 of them with brain recurrence. Two patients had ocular recurrence exclusively as their first relapse. The remaining two relapsing patients had bone lesions. One patient died intercurrently. As a result, only three patients are alive and free of disease after 16 to 36 months and all three received some adjuvant treatment in addition to whole brain irradiation.

Adult↗

[Ultrasonic tissue characterization in hypertrophic cardiomyopathy: analysis of three-layered appearance of the ventricular septum by apical approach].

In normal hearts, two-dimensional echocardiography from the apical window displays the left ventricular wall as a three-layered appearance (TLA): central bright layer and bilateral sonolucent zones. The TLA is considered to reflect the normal myocardial architecture: the predominant latitudinal fiber bundles of the midwall layer, and longitudinal or oblique ones on both sides. We analysed the TLA of the ventricular septum in 20 normal subjects, 20 patients with left ventricular hypertrophy due to pressure load (LVH), and 81 patients with hypertrophic cardiomyopathy (HCM). Of the 81 HCM patients, the layering was often obscure or absent in 53 (65%), whereas LVH patients showed clear TLA as well as normal hearts. In patients with severe layering disorder (n = 30), the age at diagnosis was lower (40 +/- 15 vs 50 +/- 12, p less than 0.05), and familial occurrence (53 vs 11%, p less than 0.01) and severe functional limitation (NYHA greater than or equal to III) were more common (27 vs 4%) than in those with clear TLA (n = 28). The disturbed layering detectable by echocardiography may reflect the disorder of basic myocardial fiber architecture in the ventricular septum, and is likely to become a useful marker of the pathologic severity of the disease.

Adult↗

Dipeptidyl aminopeptidase IV staining of cytologic preparations to distinguish benign from malignant thyroid diseases.

Staining for dipeptidyl aminopeptidase IV (DAP IV [EC: 3.4.14.5]) activity was applied to aspiration biopsy specimens or imprint preparations of surgical biopsy specimens from thyroid tumors. Material was obtained from 55 patients with histologically proven thyroid diseases: 9 with papillary carcinoma, 5 with follicular carcinoma, 11 with follicular adenoma, 13 with adenomatous goiter, 8 with Hashimoto's thyroiditis, and 9 with other benign conditions. Most tumor cells, follicular lumina in cell clusters, and intranuclear inclusions were strongly positive for DAP IV in all examples of papillary or follicular carcinoma. In contrast, only a few epithelial cells were labeled for DAP IV in follicular adenoma and adenomatous goiter. Some Hürthle cells in Hashimoto's thyroiditis also were positive for DAP IV. When a DAP IV scoring system based on the percentage of positive cells and staining intensity was used, all benign tissues except one (from a follicular adenoma) were found to have extremely low scores. These results indicate that staining for DAP IV activity is a simple but useful tool to aid in distinguishing benign from malignant thyroid neoplasms.

Adenocarcinoma↗

Hereditary transmission of tetralogy of Fallot, cardiac hypertrophy, and anomalies of great vessels in WKY/NCrj rats.

We examined 78 fetuses on d 21 of gestation (G21) and 83 neonates on d 2 after birth (A2), which were first generation offspring of WKY rats mated with normal Wistar rats (F1). In addition, we examined six groups of fetuses on d 19 of gestation (G19): 65 Wistar rats, 111 WKY rats, 85 F1, 100 F1 X F1, 92 F1 X Wistar, and 97 F1 X WKY progeny. In the F1 at G19, G21, and A2, there were abnormalities of the pulmonary valve, pulmonary outflow tract, architecture of muscle bundle, and pulmonary arterial branch, as well as hypoplastic ductus arteriosus and postnatal cardiac hypertrophy, similarly in males and females but at a lower incidence and to a lesser extent than in the WKY rats. Severe pulmonary valve dysplasia and ventricular septal defect with overriding of the aorta (tetralogy of Fallot), usually associated with a markedly small ductus, were not present or were very rare in the F1 and the F1 X Wistar but were present in the F1 X WKY and in the F1 X F1 less prevalently than in the WKY. The size of the ductus showed a continuous distribution in all of the six groups; there was a large skewing toward lower values in the WKY, the F1 X WKY, and the F1 X F1. These results suggest that cardiovascular anomalies of WKY rats are transmitted as autosomal recessive or incomplete autosomal dominant traits with an incomplete penetrance and variable expressivity or as polygenic traits. Chromosomal analysis of 31 WKY fetuses revealed no aberrations specifically related to the development of cardiovascular malformations.

Animals↗

Visualization of the heart and determination of left ventricular mass in rats by echocardiography.

A high-frequency transducer was used to determine the optimal parameters for visualizing the heart in 40 normal Wistar, 15 SHR, and 10 aorta-banded rats. The rats were 5 to 30 weeks old and weighed between 105 and 705 grams. Two-dimensional and M-mode views of the ventricles, atria, valves, and great arteries were obtained by placing the transducer beneath the rats through the left or right parasternal window in either the prone or the right decubitus positions, respectively. Left ventricular (LV) mass was determined on the basis of a spheroid model; these values correlated well with the LV weight for both the Wistar rats (r = 0.94, p less than 0.001) and the rats with cardiac hypertrophy due to pressure load (r = 0.87, p less than 0.001). These results were highly reproducible. This indicates that echocardiography is useful for obtaining quantitative measurements in rats.

Animals↗

Tetralogy of Fallot, pulmonary valve stenosis, ventricular septal defect, and hypertrophic cardiomyopathy in WKY/NCrj rats.

We examined anatomically the hearts of 198 WKY/NCrj rats of 20 litters. There were 51 rats with moderate to severe thickening of the pulmonary valve and 19 rats with a ventricular septal defect; the two lesions occurred together in 16 rats, in 15 of which there were overriding of the aorta, stenosis of the pulmonary outflow tract, and hypertrophy of the right ventricle, fulfilling the criteria for tetralogy of Fallot in man. The papillary muscle of the conus was absent in 65 rats. The heart was abnormally heavy in 18. We analyzed the relationship between cardiac hypertrophy and valvular lesions and septal defects in these rats plus 27 selected WKY rats with abnormally heavy hearts. Of the 151 rats with neither severe valvular lesions nor septal defects, six rats had abnormally heavy hearts and 67 rats had disproportionate ventricular septal thickening. This situation in the rats is similar to hypertrophic cardiomyopathy. The occurrence of these abnormalities, isolated or in association, in rats of an established inbred strain strongly suggests that they are etiologically or genetically linked, and that the rats should be a useful animal model for these diseases in man.

Animals↗

Tetralogy of Fallot, cardiac hypertrophy, pulmonary hypertension, and anomalies of great vessels in fetuses and neonates of WKY/NCrj rats.

We examined anatomically the hearts, lungs, and great vessels of 269 WKY/NCrj rats at three fetal and three neonatal stages. Severe pulmonary valve thickening was present in 16 and ventricular septal defects with overriding of the aorta in 15 of the 90 near-term fetuses and in 10 and nine, respectively, of the 79 neonates at 2-4 d of age. These abnormalities occurred together (tetralogy of Fallot) in seven of the near-term fetuses and in five of the neonates. A narrow pulmonary outflow tract was present in 55% of the fetuses and in 56% of the neonates. The wall of the pulmonary arterial branch was abnormally thick in 19% of the fetuses and in 26% of the neonates, most of which did not have septal defects. In about 80% of the fetuses, the middle latitudinal muscle bundle of the ventricular septum was not continuous with the left ventricular free wall, but rather with the right; after birth, it was discontinuous with both free walls. The heart was abnormally heavy in 49% of the 79 neonates. In about half of the heavy hearts, there were no septal defects or pulmonary valvular and arterial lesions. There were double aortic arches in four and right aortic arches in six of the total WKY fetuses and neonates; the ductus arteriosus was abnormally small in 47% and the aorta was large in 51% of the near-term fetuses. This constellation of congenital heart disease is genetic in origin, but altered by hemodynamics late in fetal life.

Animals↗

Gallbladder function and plasma cholecystokinin levels in diabetes mellitus.

Contractile motility of the gallbladder and plasma cholecystokinin (CCK) responses to egg yolk administration were studied in 28 diabetic patients and 12 normal subjects. The patients were divided into three groups: group A (n = 10) had no diabetic neuropathy, group B (n = 8) had diabetic neuropathy with little autonomic neuropathy, and group C (n = 10) had advanced diabetic autonomic neuropathy. In groups A and B, contraction of the gallbladder after egg yolk administration was not significantly different from that of normal subjects. However, in group C, gallbladder contraction was impaired (p less than 0.01-0.05), compared with that in normal subjects. After the administration of egg yolk, plasma CCK levels increased from 12.4 +/- 4.5 to 25.3 +/- 12.0 pg/ml in normal subjects. In group A, plasma CCK levels increased from 17.9 +/- 8.5 to 39.3 +/- 14.2 pg/ml, and in group B, from 15.2 +/- 5.1 to 38.3 +/- 9.9 pg/ml. In group C, however, plasma CCK levels increased from 33.1 +/- 13.9 to 72.4 +/- 31.9 pg/ml, and fasting CCK levels and responses to egg yolk were significantly higher than those in normal subjects and in groups A and B (p less than 0.01-0.05). In conclusion, this study showed that in a group of diabetic patients with autonomic neuropathy, gallbladder contraction was impaired despite the exaggerated CCK response to egg yolk.

Adult↗

[The effect of OK-432 on modifying a spontaneous lung metastasis from murine fibrosarcomas].

The authors have investigated the effect of OK-432 on the spontaneous metastasis from a murine fibrosarcoma, either an NFSA or a SANH, that had been transplanted into the right thigh of C3H mice. When the NFSA or the SANH tumors grew to 7 mm in diameter, they were irradiated with a single dose of 30 Gy and 20 Gy, respectively. A local administration of OK-432 (2.5 KE) around each of the tumors was initiated immediately after irradiation and continued twice a week. It was found that regrowth in both tumors was not modified by the OK-432, though the mean number of metastatic lung nodules per mouse from either tumor was significantly decreased. The incidence of a lung metastasis also was reduced by the OK-432 but not significantly. Further, mice that had received a SANH tumor transplant developed a lymph node metastasis in the abdominal cavity that was depressed by the OK-432.

Animals↗

[Feasibility of CHOP chemotherapy--with special reference to age, diabetes mellitus, liver cirrhosis and obesity].

Since 1982, we have performed 384 courses of CHOP chemotherapy for 89 patients with malignancy including 70 with non-Hodgkin's lymphoma, adhering to the original regimen as strictly as possible. As severe acute reactions, myelosuppression, fever, arrhythmia, hemorrhagic cystitis, and perforation of duodenal ulcer were seen. Rates of fever had no tendency to increase with advancing age. Three patients only with diabetes mellitus had no severe side effects. Three patients with liver cirrhosis showed severe myelosuppression and fever. One patient both with liver cirrhosis and diabetes mellitus died from the infection due to CHOP chemotherapy, however the other febrile patients did not have life threatening infection. Thirty three percent (11/33 courses) of the patients with obesity experienced severe myelosuppression (WBC less than 1,000), while 55% (33/60 courses) of the patients without obesity. However satisfactory treatment results were not obtained in the patients with obesity. We consider that CHOP chemotherapy is excellent in feasibility even for the aged patients or the patients with diabetes mellitus. However, we suggest that the dose of CHOP chemotherapy should be reduced for the patients with liver cirrhosis.

Aged↗

Paraplegia caused by brown tumor in primary hyperparathyroidism. Case report.

A brown tumor is a secondary disorder of bone associated with hyperparathyroidism that arises predominantly in the metacarpals, phalanges, jaw, pelvis, or femur. Rarely does this tumor involve the spine. The authors describe a case of brown tumor in primary hyperparathyroidism, causing spinal cord compression. The first step in diagnosing this lesion in an unusual site is a high index of suspicion. Essentially, this tumor is benign but emergency surgery for tumor removal is recommended in patients showing acute spinal cord compression.

Bone Diseases↗

Isolation and chemical and biological characterization of antigenic mutants of Candida albicans serotype A.

Candida albicans serotype A possesses a specific antigen designated antigenic factor 6, that resides in the mannans on the cell surface. To define the molecular structure of antigenic factor 6, as well as to determine the role of cell wall mannan in the ability of C. albicans to adhere to epithelial cells, we isolated antigenic factor 6-deficient mutants by screening with agglutinating monoclonal antibody (MAb) CA4-2 which corresponds to polyclonal antibody (PAb) factor 6. 1H-NMR spectral analyses of the purified mannans from the parent and the mutants showed loss of the signal at 4.77 ppm, corresponding to the beta-linkage of the side chain, in the mutants. Although the parent whole mannan as well as its mannohexaose fragment (M6) inhibited the agglutination reaction between C. albicans serotype A cells and MAb CA4-2, the mutant mannan showed lower inhibitory activity and a decreased amount of M6 in its acetolyzed products. These results indicate that the mutant mannan is defective in the side chain of M6 which is bound, via beta-linkage, to a branch of the inner side chains, resulting in the loss of reactivity with MAb CA4-2. Experiments on the adherence of C. albicans showed that the antigenic mutants as well as C. albicans serotype B strains, which lack antigenic factor 6, had significantly (p less than 0.01) less adherence ability than the parent strain. These results suggest that the side chains of M6 specific for C. albicans serotype A mannan are heavily involved in the adherence mechanisms as ligands.

Agglutination Tests↗

Spontaneously occurring hypertrophic cardiomyopathy in the rat. II. Distribution of, and correlations between, various cardiac abnormalities in the WKY/NCrj and its related strains.

We performed gross-anatomic and histologic examinations quantitatively on 18 male and 30 female WKY/NCrj rats, and their 299 first generation off spring. The results were analyzed in comparison with those obtained from 3 other strains of rats. The offspring of the WKY rats showed various cardiac abnormalities quite similar to those in their parents. The cardiac abnormalities in the offspring of the WKY rats were: increased heart weight (in about 10%), left or right atrial hypertrophy (50%), disproportionate septal thickening (50%), small left ventricular cavity (40%), right ventricular hypertrophy (40%), abnormal fiber arrangement greater than 5% in either of the 3 ventricular walls (90%), myocardial fibrosis (70%), and abnormal location of arteries in the ventricular septum (30%). ECG findings of the WHY-F rats such as high QRS complexes and high T waves and axis deviation showed a high sensitivity and specificity in the diagnosis of marked cardiac hypertrophy. Another conspicuous histologic finding observed in the WKY hearts was that the continuity of the latitudinal fiber bundle of the ventricular septum with that of the left ventricular free wall, an important functioning unit for pressure generation in the left ventricle, was markedly disturbed in the area of junction between the 2 walls; the smaller the continuity, the greater the cardiac hypertrophy; the disadvantage of the discontinuity for the pressure generation may be related to the development of cardiac hypertrophy. Also examined were two strains of Wistar rats with the same origin as the WKY/NCrj. These rats also had gross-anatomic and histologic abnormalities of the heart quite similar to those in the 2 generations of WKY/NCrj rats, suggesting that a common factor related to the development of the abnormalities, probably a genetic predisposition, has been transmitted in these 3 strains.

Animals↗

Spontaneously occurring hypertrophic cardiomyopathy in the rat. I. Pathologic features.

The gross anatomic and microscopic appearance of the hearts of young and adult WKY/NCrj rats was examined in comparison with that of normotensive Wistar and SHR/NCrj rats. In a substantial number of the WKY rats, the heart weight and thickness of ventricular septum were much greater than those of the Wistar and SHR rats. The ventricular septum to left ventricular free wall thickness ratio was greater than 1.3 in about one sixth of the WKY rats. In most of the hypertrophied WKY hearts, the transverse area of the left ventricular cavity was smaller in relation to the wall area than in the Wistar and SHR rat hearts, although in a few it was greater. Abnormal fiber arrangement, myocyte hypertrophy, and myocardial fibrosis were far more prominent in the hypertrophied myocardium of the WKY rats compared with the Wistar or SHR rats. Intramural arteries with marked wall thickening existed frequently in the hypertrophied and dilated hearts. Electron microscopic examination revealed marked disarrangement of bundles of myofilaments and widened Z-bands in the hypertrophied myocardium. Blood pressure was not elevated in the rats with cardiac hypertrophy. These findings show that a disease of the myocardium with the pathologic features similar to those of hypertrophic cardiomyopathy in man occurs spontaneously in rats.

Animals↗