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Biomedical subjects

T Nakata

Publications and source records attributed to T Nakata.

At least 73 records · Page 4Linked to original sources

Atomic force microscope of drug-DNA interaction.

We have been investigated the possibility of B-Z transition in ZnTMPyP-DNA interaction based on the observation of spectroscopic data. In this study, we found drastic change in the AFM image of supercoiled plasmid DNA when it was interacted with TMPyPs indicating that the considerable amount of unwinding of double helix or B-Z transition is induced by the drug-DNA interaction. Such phenomena were not observed for other cationic drugs examined.

Binding Sites↗

Prognostic value of impaired myocardial fatty acid uptake in patients with acute myocardial infarction.

Impaired cardiac fatty acid uptake, assessed by the radiolabelled fatty acid analogue beta-methyl-p-iodophenyl pentadecanoic acid (I-123-BMIPP), is observed in the myocardium following acute ischaemic events, but the long-term prognostic implication has not been established. This study aimed to determine the prognostic value of cardiac BMIPP uptake in patients with acute myocardial infarction. Following the assessment of thallium-201 and I-123-BMIPP uptake, 101 post-infarct patients were prospectively followed up with primary end points of cardiac death, heart failure and non-fatal infarction. During a mean follow-up of 28 months, three cardiac deaths, three non-fatal infarctions, 23 revascularizations and four recurrences of angina pectoris were observed. Multivariate analysis identified reduced uptake of BMIPP and perfusion, no beta-blocking treatment and greater thallium-BMIPP mismatch (i.e. larger BMIPP defect than thallium defect) as significant predictors for overall cardiac events. Prior myocardial infarction, reduced left ventricular ejection fraction and greater thallium-BMIPP mismatch were selected as independent predictors of harder cardiac events. Female patients, those with greater BMIPP defect or greater thallium-BMIPP mismatch showed worse clinical outcomes. The inclusion of BMIPP data improved the prognostic values of conventional significant predictors. In conclusion, impaired myocardial I-123-BMIPP uptake and perfusion-BMIPP mismatch are related to a high probability of fatal and non-fatal cardiac events, suggesting the aetiological relevance and prognostic value of impaired cardiac fatty acid metabolism in viable, but jeopardized, myocardium following acute myocardial infarction.

Adult↗

Does primary stenting preserve cardiac function in myocardial infarction? A case-control study. NORTH-981 investigators. Network of revascularisation therapy in Hokkaido.

OBJECTIVE: To investigate whether coronary stenting limits myocardial injury and preserves left ventricular function. DESIGN AND SETTING: Prospective multicentre case-control study of primary percutaneous transluminal coronary angioplasty (PTCA) with and without stenting, performed in seven cardiovascular centres. SUBJECTS AND METHODS: 45 consecutive patients with acute myocardial infarction who were treated with successful primary stenting (Stent group) and did not have restenosis were paired with 45 matched control subjects with acute myocardial infarction treated by successful primary PTCA without stenting, also with no restenosis (POBA group). RESULTS: In comparison with the POBA group, the Stent group-especially those patients with a left anterior descending coronary artery lesion-had a smaller hypokinesis area (mean (SD): 15. 1 (20.0) v 34.4 (24.3) chords), reduced hypokinesis area/risk area (25.2 (31.9)% v 58.8 (40.1)%), and a larger ejection fraction (63.3 (10.2)% v 51.7 (11.7)%) evaluated by quantitative left ventriculography using the centerline method. In the Stent group, the correlation between risk area and hypokinesis area was significantly shifted downward. Multiple logistic regression analysis on infarct size limitation (hypokinesis area/risk area < 50%) identified preinfarction angina in all subjects and preinfarction angina and stenting in patients with left anterior descending coronary artery lesions as explanatory factors. CONCLUSIONS: Primary PTCA using a coronary stent is effective in preventing myocardial injury and restoring left ventricular function in patients with anterior acute myocardial infarction.

Adult↗

Hypoparathyroidism potentiates cardiovascular complications through disturbed calcium metabolism: possible risk of vitamin D(3) analog administration in dialysis patients with end-stage renal disease.

BACKGROUND/AIM: Progressive cardiovascular calcification in dialysis patients with end-stage renal disease (ESRD) is a serious complication; however, the precise mechanism remains uncertain. We tested whether metabolic calcium abnormalities and hypoparathyroidism might have a correlation with cardiovascular complications in ESRD patients. METHODS: A series of 48 ESRD patients with cardiovascular diseases and/or congestive heart failure, aged 36-82 (61 +/- 12) years, 23 male and 25 female, were enrolled in this study. Serum total calcium (Ca, mmol/l), inorganic phosphate (mmol/l), and intact parathyroid hormone (iPTH, pg/ml) levels were determined in all cases. RESULTS: Organic heart disease was confirmed in 28 patients (58.3%), including 15 with coronary artery disease: 8 with aortic aneurysm, 8 with stenotic valvular heart disease, 9 with excessive mitral annular calcification, 3 with dialysis cardiomyopathy, and 7 with obstructive arterial disease. Serum iPTH measurement revealed hypoparathyroidism (iPTH <60) in 20 of 48 (41.7%) and hyperthyroidism (iPTH >/=200) in 13 of 48 (27.1%) subjects. The 20 patients with low iPTH had a higher prevalence of valvular heart disease, a higher total Ca level corrected for serum albumin (2.70 +/- 0.30 in low iPTH vs. 2.47 +/- 0.30 in normal iPTH, 2.35 +/- 0.20 in high iPTH, p = 0.003) and a higher tendency of vitamin D(3) analog use (65% in low iPTH vs. 33% in normal iPTH and 46% in high iPTH, p = 0.078). Moreover, corrected serum Ca exhibited a negative logarithmic correlation with serum iPTH: corrected Ca = -0.284x log (iPTH) + 3.021 (r = 0.637, p = 0.0001). Multiple logistic regression analysis revealed diabetes and hypoparathyroidism (iPTH <60) as risk factors for cardiovascular complications in ESRD. CONCLUSION: These results suggest that hypercalcemia and hypoparathyroidism in conjunction with vitamin D(3) use might play an important role in cardiovascular complications of chronic dialysis patients.

Adult↗

Technetium-99m sestamibi/tetrofosmin myocardial perfusion scanning in cardiac and noncardiac sarcoidosis.

Left ventricular (LV) and right ventricular (RV) involvement in sarcoidosis must be firmly confirmed to determine patients' prognosis. We examined whether myocardial perfusion images using technetium-99m single photon emission computed tomography (SPECT) have a diagnostic benefit in the evaluation of biventricular involvement. Sixteen patients with sarcoidosis, aged 21-78 (54 +/- 12) years old, 5 males and 11 females, complicated with cardiac disease (cardiac sarcoidosis, n = 6) including tachyarrhythmias of ventricular origin (n = 5), atrioventricular block (n = 4), and congestive heart failure (NYHA > or = II, n = 1), were enrolled in this study. Myocardial SPECT using technetium-99m sestamibi or tetrofosmin was performed and semiquantitatively scored for comparison with 25 control subjects. Perfusion abnormalities were more frequently recognized in sarcoidosis (LV 5/16, 31% and RV 14/16, 88% vs. LV 0/25, 0% and RV 8/25, 32% in controls). LV involvement had a close correlation with atrioventricular block and with congestive heart failure, and multiple sites of RV involvement correlated with ventricular tachyarrhythmia of RV origin. Total number of defect segments were highest in cardiac sarcoidosis (18/30, 60% vs. 19/60, 32% in noncardiac sarcoidosis, and 11/150, 7% in controls, p = 0.0001), and semiquantitatively evaluated total LV and RV scores (ranging from 0 to 18) were higher than those of controls (15.1 +/- 1.8 vs. 11.4 +/- 3.0 in noncardiac sarcoidosis, and 9.0 +/- 5.0 in cardiac sarcoidosis) and exhibited a significant positive linear correlation with the RV ejection fraction (y = 19.8 + 1.83x, r = 0.786, p = 0.001). Biventricular SPECT using technetium-99m is clinically useful for the noninvasive evaluation of both ventricular involvements in sarcoidosis.

Adult↗

The C-terminal tail domain of neurofilament protein-H (NF-H) forms the crossbridges and regulates neurofilament bundle formation.

In order to study the role of NF-H in a neurofilament network formation in neurons, we coexpressed NF-H with neurofilament protein-L (NF-L) in Sf9 cells using the baculovirus expression system. Electron microscopy observations revealed that parallel arrays of 10 nm filaments with frequent crossbridges between adjacent filaments were formed in the cytoplasm of Sf9 cells infected with the recombinant virus that co-expressed NF-L and NF-H. To explore the function of the C-terminal tail domain of NF-H, various deletion mutants lacking portions of the tail domain were constructed, and each of them was coexpressed with NF-L. The results show that the tail domain of NF-H is a structural component of crossbridges and is involved in parallel bundle formation of neurofilaments, as core filaments of the axon. The last 191 amino acids of the C-terminal tail domain of NF-H play a key role in crossbridge formation.

Animals↗

[A simultaneous operation on coronary artery disease and abdominal aortic aneurysm during extracorporeal circulation in patient with impaired left ventricular function].

A 74-year-old man had an previous antero-septal and inferior myocardial infarction and an abdominal aortic aneurysm (AAA) 48 mm in diameter. Coronary angiography showed obstruction of the left anterior descending artery and of the right coronary artery, and 95% stenosis of the circumflex artery. The value of an ejection fraction of the left ventricle was 33%, measured by left venticulography. CABG and replacement of the aneurysm were performed simultaneously, because of the necessity of an intra-aortic balloon pumping (IABP) due to the impaired left ventricular function. First, CABG was performed under cardiac arrest. After declamping the ascending aorta, subsequently, replacement of AAA was performed while extracorporeal circulation (ECC) assisted heart beating. Weaning from ECC was smooth, and the operation was successful without using IABP. The patient was discharged 32 days after the operation. Consequently, cardiopulmonary bypass during AAA operation could decrease heart loads when hemodynamic states change in aortic clamping or after declamping. A simultaneous operation of CABG and AAA using ECC is safe and effective for impaired left ventricular function.

Aged↗

[A case of spinal muscular atrophy with marked calf hypertrophy and adolescent onset].

We report on a 41-year-old male patient with spinal muscular atrophy (SMA). He had slowly progressive muscular weakness and hypertrophic calves since 14 years of age. The upper arms were slightly, and the thighs moderately atrophic, but the calves were remarkably hypertrophic. There was muscle weakness of both the upper and lower limbs, being more proximal in distribution. He had a positive Gowers' sign and his gait was slightly waddling. Serum creatine kinase level was elevated (518IU/l). Electromyogram revealed a neurogenic pattern. Muscle biopsy of the left biceps brachii showed chronic neurogenic changes. Immunohistochemical examination and Western blot analysis using anti-dystrophin antibodies showed no abnormality. DNA analysis with multiplex PCR proved no deletion in the dystrophin gene, while deletions of exons 7 and 8 of the telomeric copy of survival motor neuron gene were detected. In 1978, Pearn et al. described a new variant syndrome of SMA, characterized by adolescent onset, gross hypertrophy of calves, and a slowly progressive clinical course. The present case is compatible with this syndrome. Therefore, it is suggested that this syndrome, mimicking Becker muscular dystrophy, is not an independent clinical entity, although the phenotype of this syndrome is different from that of typical SMA.

Adolescent↗

[Intracardiac floating thrombi in patients with acute pulmonary thromboembolism].

The mortality and morbidity associated with residual intracardiac floating thrombi in patients with acute pulmonary thromboembolism remain uncertain. Thirteen patients (2 men and 11 women, mean age 56 +/- 15 years) with pulmonary thromboembolism underwent echocardiography within 24 hours from onset of symptoms. Four patients (31%) had floating intracardiac thrombi in the right heart: 3 in the right atrium and one in the inferior vena cava. The time to evaluation by echocardiography was shorter than in the patients without thrombi. The thrombi disappeared shortly (3.2 +/- 2.4 hr) after thrombolysis without adverse effects in these patients. After thrombolysis, clinical symptoms improved and pressure gradient between the right ventricle and right atrium decreased significantly (p < 0.01) from baseline 47 +/- 6 to 26 +/- 5 mmHg. Major bleeding complications occurred in 3 (43%) of the patients who underwent thrombolysis. Right-side intracardiac floating thrombus was easily detectable by early echocardiography. Thrombolytic agents are likely to be effective in patients with intracardiac floating thrombi.

Acute Disease↗

Total synthesis of a new cytotoxic acetogenin, jimenezin, and the revised structure.

The first total synthesis of jimenezin was achieved by using carbohydrates as chiral building blocks, thus revising the proposed structure 1 to 2. The key steps in this synthesis include an efficient construction of the THP-THF fragments 3 and 16 through a stereoselective condensation between the pyranyl aldehyde 5 and the acetylene derivative 6, and a palladium-catalyzed coupling reaction of 3 or 16 with a terminal butenolide 4.

Antineoplastic Agents, Phytogenic↗

Prolactin secretion in response to prolactin-releasing peptide and the expression of the prolactin-releasing peptide gene in the medulla oblongata are estrogen dependent in rats.

Prolactin-releasing peptide (PrRP), recently isolated from bovine hypothalamus as an endogenous ligand to a seven transmembrane-domain orphan receptor, is a candidate specific prolactin-releasing factor. The prolactin-releasing activity of the peptide and the expression of the PrRP gene were examined in vivo in relation to estrogen status. Plasma prolactin levels increased significantly with a peak at 5 min after the administration of 50 microg/kg PrRP in female rats in estrus under urethane anesthesia as compared with those in vehicle-treated control rats, but not in female rats in diestrus or proestrus or in male rats. In ovariectomized rats treated with supraphysiological concentration of estrogen, a dose-dependent increase of prolactin secretion in response to 2-50 microg/kg PrRP was observed. However, the peak values induced by 50 microg/kg PrRP were much less than those induced by 2 microg/kg thyrotropin-releasing hormone (TRH). PrRP mRNA levels in the medulla oblongata were decreased by ovariectomy and increased by estrogen treatment. The data indicate that estrogen is prerequisite to the stimulatory effect of PrRP on the secretion of prolactin and to the increase of PrRP mRNA levels in the medulla oblongata. The weak in vivo potency of PrRP on prolactin secretion relative to TRH suggests that PrRP differs from the classical hypophysiotropic hypothalamic releasing hormones.

Animals↗

Total synthesis of reveromycin B.

[formula: see text] The stereoselective total synthesis of reveromycin B (2), a novel polyketide-type antibiotic, has been accomplished.

Anti-Bacterial Agents↗

Cellular localization of prolactin-releasing peptide messenger RNA in the rat brain.

Prolactin-releasing peptide (PrRP), a novel peptide identified as the endogenous ligand for an orphan receptor isolated from the pituitary, is a potent stimulator of prolactin release. To get a clue of the functional roles of the peptide, we performed in situ hybridization histochemistry for PrRP mRNA to define the cellular localization of PrRP-producing cells in the brain of the cycling adult female rat during diestrus. The PrRP mRNA-containing cells were located in the caudal part of the dorsomedial nucleus of the hypothalamus. In the brainstem, the cells were found in the caudal part of the solitary tract nucleus and in the caudal ventrolateral medulla (ventrolateral intermediate reticular field). Specific signals for PrRP mRNA were not detected in other brain regions. Although PrRP is a candidate for being a hypophysiotropic specific releasing factor, the discrete distribution of PrRP in the extrahypothalamic area suggests that the peptide has other physiological functions in the central nervous system.

Animals↗

Fusion of a novel gene, ELKS, to RET due to translocation t(10;12)(q11;p13) in a papillary thyroid carcinoma.

In papillary thyroid carcinomas, the genes for receptor-type tyrosine kinase, RET or TRKA, are sometimes rearranged, resulting in fusion of its tyrosine kinase domain to 5' portions of several activating genes. In a papillary thyroid carcinoma, we identified a novel gene (ELKS), the 5' portion of which is fused to the RET gene by gene rearrangement due to the translocation t(10;12)(q11;p13). Subsequent cloning of the ELKS cDNA revealed that ELKS encodes a novel 948 amino acid peptide and is expressed ubiquitously in human tissues. The presence of multiple coiled-coil domains in the ELKS product suggests that the ELKS protein forms dimers. Since the tyrosine kinase of RET is activated by dimerization that occurs when its ligands bind to the receptor, fusion of RET with the 5' dimerization domains of ELKS would activate its cytoplasmic tyrosine kinase constitutively in papillary thyroid carcinomas.

Amino Acid Sequence↗

Limitations of spontaneous reperfusion and conventional medical therapy to afford myocardial protection through antecedent angina pectoris in acute myocardial infarction.

Despite the cardioprotective effect of rapid coronary reperfusion, the effects of spontaneous recanalization on myocardial viability and metabolism are unknown. We studied whether preinfarction angina affords cardioprotection when spontaneous coronary reperfusion occurred in acute infarct patients. Myocardial tomographies with thallium and I-123-labeled-beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) were performed in 27 acute myocardial infarct patients treated medically: 15 patients had preexisting angina before infarction (group A) and 12 did not (group B). Thallium and BMIPP abnormalities and regional function were quantified by a polar map and contrast ventriculography, respectively. There was no significant difference between thallium and BMIPP in the severity index in groups A and B (89 +/- 97 vs. 85 +/- 68, 97 +/- 28 vs. 95 +/- 27, respectively), and no significant difference between the groups in the thallium or BMIPP severity index. The ratio of the thallium severity index to that of BMIPP and the regional wall-motion abnormality index were identical in groups A and B. Both patient groups were divided into 2 subgroups based on the presence or absence of spontaneous coronary reperfusion: subgroups A1 and A2, and subgroups B1 and B2, respectively. There were no significant differences among the 4 subgroups in severity indexes for both tracers, the thallium/BMIPP ratio, or the asynergy score. The BMIPP severity index correlated significantly with that of thallium in all subgroups, but no significant difference between the regression lines was found. It is therefore unlikely that spontaneous coronary recanalization affords beneficial effects through preservation of myocardial viability in an ischemia-related zone, suggesting that the cardioprotective effect of preinfarction angina is a limited phenomenon in patients undergoing rapid coronary reperfusion.

Adult↗

Expression of goose parvovirus VP1 capsid protein by a baculovirus expression system and establishment of fluorescent antibody test to diagnose goose parvovirus infection.

The gene encoding VP1 capsid protein of a goose parvovirus was cloned into a baculovirus transfer vector and a recombinant baculovirus was produced. The recombinant virus expressed a protein of 88 kDa corresponding to the molecular weight of VP1 protein and the protein was detected by immunoblotting. By indirect fluorescent antibody (IFA) test, the expressed protein was detected in the nucleus of the insect cells as big granules and electron microscopy also showed several big granules in the nucleus infected with the recombinant virus. The IFA test was developed for screening antibody in Muscovy ducks.

Animals↗

Ret/PTC3 is the most frequent form of gene rearrangement in papillary thyroid carcinomas in Japan.

Rearrangements of the RET and TRK proto-oncogenes, which generate fusion oncogenes, are frequent in papillary thyroid carcinomas in Caucasian populations. To determine the spectrum of gene rearrangements in Japanese patients, we systematically examined 40 papillary thyroid carcinomas for all possible types of gene fusion events involving RET or TRK genes. RET rearrangements were found in ten tumors (25%): ret/PTC1 had occurred in two tumors, ret/PTC2 in one, ret/PTC3 in six, and a novel RET rearrangement in the remaining patient. In this last patient, the 5' novel sequence was fused in-frame to the RET amino acid sequence; thus, the fusion gene may encode a protein with a RET kinase domain at the carboxy terminus. The RET gene was fused to 5' donor sequences at the beginning of exon 12 in all ten tumors. No rearrangements involving the TRK gene were found in this panel of carcinomas. Our results indicated that constitutive activation of the RET by gene rearrangement is a frequent mechanism of papillary thyroid carcinogenesis in Japanese adults.

Adult↗