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Biomedical subjects

T Kanaya

Publications and source records attributed to T Kanaya.

At least 55 records · Page 3Linked to original sources

Telomerase activity in gynecological tumors.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends using an RNA component as a template. Extension of telomeric repeats by telomerase prevents telomere shortening with cell divisions and contributes to chromosomal stability, possibly leading to immortalization of the cells. In the present study, we determined the telomerase activity of gynecological tumors and cell lines using a newly developed non-radioisotope telomeric repeat amplification protocol. A total of 21 cell lines derived from cervical cancer, endometrial cancer, ovarian cancer, and choriocarcinoma was examined, and all lines were found to be positive for telomerase activity, although the activity varied among cell types. A total of 50 gynecological malignant tumors was also examined, and 10 of 12 (83%) cervical cancers, 12 of 13 (92%) endometrial cancers, 18 of 21 (86%) ovarian cancers, 2 of 2 tubal cancers, and 1 of 1 vulvar cancer were found to be positive for telomerase activity. A total of 88% of gynecological tumors tested was thus found to be telomerase positive. However, no significant correlation was observed between telomerase activity and clinical features for any tumor type, although ovarian tumors expressing high telomerase activity tended to be more invasive. In contrast to that in malignant tumors, telomerase expression was weak and less common in premalignant lesions, with 5 of 7 cervical intraepithelial lesions and 4 of 6 borderline ovarian tumors exhibiting faint activity. Nine benign uterine lesions were also examined, and all were negative for telomerase activity except 1 uterine myoma, which had a weak signal. Three benign ovarian cysts examined had weak telomerase activity. These findings suggest that telomerase activation is common in gynecological malignant tumors and may be a critical step in their pathogenesis. However, premalignant lesions and some types of benign tumors also express weak telomerase activity.

Female↗

Control of the head in response to tilt of the body in normal and labyrinthine-defective human subjects.

1. Head movement responses to discrete, unpredictable tilts of the trunk from earth upright were studied in normal and labyrinthine-defective (LD) subjects. Tilts of the seated, restrained trunk, were delivered in pitch and roll about head-centred axes and approximated raised cosine displacements with peak amplitudes of 20-30 deg and durations of 1.5-2 s. Subjects performed mental arithmetic with eyes closed or read earth-fixed text. 2. At the onset of tilt the head momentarily lagged behind the trunk because of inertia. Subsequently, head control varied widely with three broad types: (i) head relatively fixed to the trunk (in normal subjects and some patients); (ii) head unstable, falling in the direction of gimbal tilt (typical of acute patients for pitch motion); (iii) compensatory head movement in the opposite direction to gimbal tilt (observed consistently in normal subjects and in well-adapted patients). 3. EMG was well developed in subjects with compensatory head movement and consisted of an initial burst of activity at minimum latencies of 25-50 ms (means 72-108 ms), followed by a prolonged peak; both occurring in the 'side up' neck muscles, appropriate for righting the head. These muscles are shortened during the initial head lag so the responses cannot be stretch reflexes. In normal subjects their origin is predominantly labyrinthine but in patients they may be an 'unloading response' of the neck. 4. Head stability in space was superior with the visual task for all subjects but vision only partially compensated for labyrinthine signals in unstable patients. 5. Modelling the responses to tilt suggests that, in LD subjects, the short-latency burst could be driven by signals from the neck of the relative acceleration between head and trunk tilt. The longer latency EMG could be driven by a signal of head tilt in space. Normally, this signal is probably otolithic. In patients it could be synthesized from summing proprioceptive signals of position of head on trunk with trunk tilt.

Adaptation, Physiological↗

Characterization of the truncated thrombopoietin variants.

Thrombopoietin (Tpo) is a specific cytokine which regulates megakaryocyte differentiation and maturation. We isolated a truncated mouse Tpo cDNA, the product of which turned out to function neither as an active Tpo variant nor as an antagonist. To define the functional domains of the Tpo molecule further, various truncated and point-mutated Tpo molecules were prepared and their biological activity was assayed. It was found that deletion of the amino terminal side of a potential proteolytic cleavage site, Arg-Arg motif, caused complete loss of Tpo's activity, and that point-mutants lacking one of four conserved cysteine residues lost Tpo activity. We also noticed that Tpo activity was inhibited by the reducing agent. Thus, it was concluded that the amino terminal half of the Tpo is sufficient for Tpo activity, and that the cysteine residues, especially the last cysteine residue located two amino acids away from the Arg-Arg motif, are critical for this activity.

Amino Acid Sequence↗

Isolation of p10 gene from Bombyx mori nuclear polyhedrosis virus and study of its promoter activity in recombinant baculovirus vector system.

A homologue of Autographa californica NPV (AcNPV) p10 gene was identified and cloned from Bombyx mori NPV (BmNPV). BmNPV p10 gene encodes truncated protein of 70 amino acid residues that lacks carboxyl terminus comparing with the p10 protein encoded by AcNPV. The putative TATA box sequence and the ATAAG motif which is the consensus sequence of baculovirus very late promoter were conserved. A transfer vector, pBNT1, which includes the p10 promoter region of BmNPV for foreign gene expression was constructed. By using pBNT1, a recombinant BmNPV, Bmp10-Luc, in which the p10 gene was replaced by the firefly luciferase gene, was obtained. We also obtained another recombinant virus, BmPH-Luc, in which the polyhedrin gene was replaced by the luciferase gene. The luciferase activity detected in BoMo-15AIIc insect cells infected with Bmp10-Luc was approximately 50% of that infected with BmPH-Luc, suggesting that although both the p10 and polyhedrin promoters of BrnNPV are effective in high-level expression of foreign genes, the p10 promoter is not so strong as the polyhedrin promoter.

Amino Acid Sequence↗

Expression and characterization of human bone morphogenetic protein-2 in silkworm larvae infected with recombinant Bombyx mori nuclear polyhedrosis virus.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) was expressed in silkworm larvae, and a milligram quantity of the protein was purified and characterized. The expressed rhBMP-2 was biologically active in terms of induction of alkaline phosphatase activity in MC3T3-E1 cells and ectopic bone formation in mice. On SDS-polyacrylamide gel electrophoretic analysis, the purified protein showed a 16 kDa band under reducing conditions and a 30 kDa band under non-reducing conditions. The silkworm-expressed rhBMP-2 was glycosylated and susceptible to endo-beta-N-acetylglucosaminidase F (endo F) and endo H, but resistant to endo D. Deglycosylated rhBMP-2 treated with endo F retained its biological activity. These results suggest that rhBMP-2 exists as a dimer and disulfide bond(s) are responsible for the dimerization. Moreover, sugar chains have no direct effect on the biological activity of the protein. The availability of a quite large amount of rhBMP-2 has allowed us to study the biological function of this interesting factor in detail.

3T3 Cells↗

[A case of acute isolated (Fiedler's) myocarditis diagnosed by histopathological study with rapid unfortunate course].

A 65 year-old-man was admitted to our hospital complaining of orthopnea and precordial oppressive feeling. Chest roentgenogram revealed congestive heart failure. Electrocardiogram revealed acute myocardial infarction-like pattern. Serum enzymes (CPK, GOT, LDH) were slightly elevated, but serum antiviral antibodies were not elevated. Echocardiogram showed severe symmetrical left ventricular (LV) hypertrophy, but there was no abnormality of LV wall motion. He died of progressive heart failure and ventricular fibrillation on the second hospital day. A necropsy was performed within one hour of death. The heart was enlarged (690 g) with both left and right ventricular hypertrophy. The myocardium disclosed a diffuse infiltration predominantly of eosinophilic leucocytes. Histopathological study revealed giant cell formation and granulomatous lesions in the myocardium. There was no overt endocarditis or pericarditis. We concluded that the severe LV hypertrophy was due to myocardial inflammatory swelling. From these findings, we diagnosed this case as acute isolated (Fielder's) myocarditis.

Acute Disease↗

Regional cerebral blood flow in depression.

Regional cerebral blood flow (rCBF) was measured in patients with endogenous depression by the single photon emission computed tomography (SPECT) using N-isopropyl-p-[123I]iodoamphetamine (IMP). The subjects were 32 patients with endogenous depression and 20 normal controls. These 32 patients, who were divided into 10 unmedicated group and 22 medicated group, were reexamined when the depressed patients reverted to a euthymic state (remission). The value of rCBF was assessed by the corticocerebellar ratio (CCR), which was expressed as a ratio of activity per pixel in the cerebral regions of interests (ROIs) to the activity per pixel in the cerebellum. The depressive patients showed a decrease in rCBF all over the cerebral regions and, especially, the lower rCBF in the left than in the right hemisphere. These changes turned toward normal in a remitted state following treatments, though there was no significant difference in rCBF between the medicated and unmedicated patients. There was a significantly negative correlation between the severity of depressive symptoms and the mean rCBF in a total of patients with depression. These results suggest that psychiatric symptoms in the depressive patients might be related to the left hemispheric dysfunction.

Adult↗

[Studies on the preparation and evaluation of Kijitsu, the immature citrus fruits. III. Relation between diameter of Kijitsu and synephrine content].

For the purpose of evaluating Kijitsu, the content of synephrine in dried unripe citrus fruits was analyzed by high performance liquid chromatography after cleaning up the MeOH extract with an ion exchange cellulose column. Among them, Citrus unshiu had the highest amount of synephrine. No difference was found between C. hassaku and C. aurantium. The synephrine content decreased corresponding with an increase in diameter of Kijitsu.

Chromatography, High Pressure Liquid↗

Relationship of thallium-201 defect and left ventricular function after dipyridamole infusion.

Tl-201 imaging and first-pass radionuclide ventriculography (RNV) by 4 min infusion of 0.56 mg/kg dipyridamole were performed on 22 patients with coronary artery disease in order to know the relationship of myocardial perfusion and left ventricular function after dipyridamole-infusion, and thereby to define whether Tl-201 defect with dipyridamole could imply myocardial ischemia. Initial and delayed Tl-201 images were divided into anterior, apical, and infero-posterior segments, and segmental perfusion defects were categorized as reversible, fixed and no defect. RNV on the 30-degree right anterior oblique view was also divided into anterior, apical, and infero-posterior wall to be evaluated for regional wall motion by a 5 point score before and after dipyridamole. Changes in left ventricular ejection fraction (LVEF) with dipyridamole were also calculated. Normal responses of regional wall motion and LVEF to dipyridamole were established from the data of 14 normal subjects. Reversible defects were closely associated (69%) with an abnormal response of regional wall motion (score decrease of 1 or more after dipyridamole). Both fixed defects and no defects showed little association with abnormal response of regional wall motion. Moreover, 77% of the patients having reversible-defect segment showed an abnormal response of LVEF (reduction of 3% or more following dipyridamole). However, patients without reversible defect did not show an abnormal response to dipyridamole. These results suggest that dipyridamole-induced Tl-201 defects represent a myocardial ischemia which causes a reduction of ventricular function.

Adult↗

[Primary malignant mesothelioma of the pericardium masquerading as malignant pleural mesothelioma: report of an autopsy case and review of the reported cases in Japan as to its invasion to neighboring organs].

The Patient was a 72-year-old man who presented with dyspnea and general fatigue. Chest X-ray and CT-scan at the admission showed bilateral pleural effusion with collapse of the left lung and pericardial effusion. Cytology from the left pleural effusion suggested malignant mesothelioma. For this reason, malignant mesothelioma of the left pleura was diagnosed clinically and it was supposed to have spread subsequently to the pericardium. At autopsy, entire surface of the heart was found to be encroached in a diffuse fashion by a thick layer of mesothelioma tissues, which formed a small mass around the left pulmonary vein over the left atrium and invaded deep into the myocardium of all cardiac chambers. The endocardium and the intima of the left pulmonary vein were free of the invasion. The parietal pericardium adhered in places to the cardiac lesion, but no direct invasion to the adjacent pleurae through the pericardial wall was present. The left pleura over the lung and chest cavity disclosed only a superficial invasion by similar mesothelioma which was identifiable only on microscopic study. No distant metastasis was present in any thoracic and other organs as well as lymph nodes including the hilar ones of the lung. It seemed most likely from this anatomical finding that the primary site of the present mesothelioma was in the pericardium (visceral) and the tumor spread to the left pleura by a continuous extension along the outside of the left pulmonary vein. Primary malignant mesothelioma of the pericardium is of very rare occurrence and we found only 51 cases of it in the Japanese literature since 1915.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗