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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 55 records · Page 3Linked to original sources

Endo- and aminopeptidase activities of rat cathepsin H.

Employing soluble denatured protein substrates and their derivatives, the proteolytic activity of rat cathepsin H was investigated. The enzyme showed aminopeptidase activity which sequentially released amino acid from the N-terminal of the substrate. The aminopeptidase activity did not act on N alpha-acetylated peptides and showed moderate ionic-strength dependence when methionyl-methylcoumarylamide was employed as a substrate. These results indicate that the activity essentially requires an N-terminal free amino group of the substrate and recognizes it electrostatically to some extent. On the other hand, the enzyme was also indicated to exhibit endopeptidase activity by employing appropriate N alpha-acetylated peptide substrates. In contrast to the aminopeptidase activity, the endopeptidase activity showed rather strict specificity, preferring hydrophobic residues at P2 and P3 sites. Because of the broad specificity and high efficiency of the aminopeptidase activity, it was difficult to directly observe endopeptidase activity in the digestion of large peptide substrates with a free alpha-amino terminal. Thus, this is the first experimental evidence that indicates endopeptidase activity by assigning internal peptide bonds cleaved by this activity. From this data, we proposed a model of the binding site of this enzyme.

Amino Acid Sequence

Relaxant response of isolated basilar arteries to calcitonin gene-related peptide in stroke-prone spontaneously hypertensive rats.

The relaxant effects of calcitonin gene-related peptide (CGRP) and other drugs were compared in basilar artery rings obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). In addition, the relaxant effect of CGRP on basilar arteries from spontaneously hypertensive rats (SHR) was examined. Relaxation induced by CGRP was independent of the presence of endothelium, and it was markedly increased in SHRSP when compared to WKY. In contrast, acetylcholine-induced relaxation was endothelium-dependent and did not differ between the two groups. Enhanced CGRP-induced relaxation was also found in SHR when compared to WKY. However, the relaxant response was greater in SHRSP than in SHR. No significant differences were found in the relaxation induced by isoproterenol, forskolin, dibutyryl cyclic AMP, and 3-isobutyl-1-methylxanthine in endothelium-rubbed arteries of WKY and SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the rat basilar artery, and that the enhanced CGRP-induced relaxation found in SHRSP may not be associated with alterations of vasodilation mediated by cyclic AMP.

1-Methyl-3-isobutylxanthine

Characterization of the insulin resistance in liver cirrhosis: a comparison with non-insulin dependent diabetes mellitus.

To characterize the mechanisms of insulin resistance in liver cirrhosis (LC), we estimated the peripheral tissue sensitivity and responsiveness to insulin using the euglycemic clamp technique and determined the insulin binding to erythrocytes in patients with compensated LC as well as in patients with non-insulin dependent diabetes mellitus (NIDDM). The insulin dose-response curves of the glucose metabolic clearance rates (MCR) were shifted to the right and downward both in patients with LC and NIDDM, indicating a reduced sensitivity and responsiveness to insulin. In the cirrhotics, MCR at the maximally effective insulin level, an index of insulin responsiveness, was correlated with fasting insulin levels (r = -0.57, P < 0.01) and sigma BG in 75 gOGTT (r = -0.43, P < 0.05), but no correlations were found between them and the diabetics. Although specific insulin bindings to erythrocytes were significantly lower in patients both with LC and NIDDM, Scatchard analysis revealed a significant decrease in the number of insulin receptors in the cirrhotics, and a decrease in the empty-site affinity in the diabetics. These findings suggest that insulin resistance in LC consists of a combination of binding and postbinding defects. The latter defect may be caused by basal hyperinsulinemia and contribute to the development of glucose intolerance. Although binding and postbinding abnormalities are also found in NIDDM, the mechanisms of insulin resistance in LC and NIDDM may be different.

C-Peptide

Delayed postcontrast CT and MR imaging of chondroid chordoma--case report.

A rare case of intracranial primary chondroid chordoma is reported with special reference to neuroradiological findings. A precontrast computed tomographic (CT) scan revealed an isodense mass with multiple flecks in the right cerebellopontine region. A postcontrast CT scan showed slight ring enhancement. A delayed postcontrast CT scan demonstrated marked homogeneous enhancement extending from the middle cranial fossa to the cerebellopontine region on the right. Magnetic resonance (MR) imaging demonstrated a well-defined lesion as a high-intensity mass on T2-weighted image and a low-intensity mass on T1-weighted image. A MR image 5 minutes after gadolinium-diethylenetriaminepenta-acetic acid administration showed heterogeneous enhancement. A MR image 30 minutes after the contrast administration showed more marked, homogeneous enhancement. Such delayed postcontrast CT and MR imaging are useful in the differentiation of chondroid chordoma from classical chordoma.

Aged

Suprasellar malignant teratoma with 11-year survival--case report.

Long-term survival of malignant teratoma is rare. A 16-year-old female with a suprasellar malignant teratoma survived for 11 years before succumbing to embryonal carcinoma. A suprasellar immature teratoma with increased serum alpha-fetoprotein level was verified histologically. Radiation therapy and combined chemotherapy were given after partial removal. Eleven years later, the primary lesion recurred as embryonal carcinoma.

Adolescent

The embryologic development of the human external auditory meatus. Preliminary report.

During the final period of embryogenesis, a funnel-shaped tube continues medially into the mesenchymal tissue forming a curved path. Although this may sound simple, the development occurring during early fetal life is in fact very complex. At first, ectodermal cells proliferate to fill the lumen of the meatus, forming the meatal plug, and then at 10 weeks the bottom of the plug extends in a disc-like fashion, so that in the horizontal plane the meatus is boot-shaped with a narrow neck and the sole of the meatal plug spreading widely to form the future tympanic membrane medially. At the same time, the plug in the proximal portion of the neck starts to be resorbed. In the 13-week fetus, the disc-like plug begins to show signs of its final destiny; the innermost surface of the plug in contact with the anlage of the malleus is ready to contribute to the formation of the tympanic membrane. In the 15-week fetus, the innermost portion of the disc-like plug splits, leaving a thin ectodermal cell layer of immature tympanic membrane. The neck of the boot forms the border between the primary and secondary meatus, and is the last part to split. In the 16.5-week fetus, the meatus is fully patent throughout its entire length, although the lumen is still narrow and curved. In the 18-week fetus, the meatus is already fully expanded to its complete form.

Cartilage

Simultaneous determination of hydrogen, methane and carbon dioxide of breath using gas-solid chromatography.

The analysis of respiratory hydrogen and methane was estimated as a useful index of intestinal fermentation of undigestible carbohydrate. A simultaneous and precious analysis of these gases as well as carbon dioxide was studied. A gas-impermeable multi-laminated film bag metalized by aluminum vapor was fitted to use as a storage bag; its impermeability was verified by measuring the residual rate of hydrogen after 3 months' storage. Hydrogen, methane and carbon dioxide of the breath gas even at 1 ppm could be determined simultaneously by using a gas-solid chromatography installed with a photoionization detector and active carbon column. To observe the genesis of hydrogen and methane after carbohydrate ingestion, pectin, a typical water-soluble dietary fiber, was fed to healthy volunteers. Increasing excretion of pulmonary hydrogen or methane showed the sign of intestinal fermentation as the results of carbohydrate malabsorption.

Adult

Syntheses and activities of some bactobolin derivatives.

Some derivatives of bactobolin were prepared from bactobolin by dehydration or substitution reactions through tris(dimethylamino)alkoxyphosphonium salt formation. A derivative with low toxicity, 6-deoxybactobolin, showed moderate activity against Gram-positive and Gram-negative bacteria including methicillin-resistant Staphylococcus aureus.

Animals

Totally synthetic analogues of siastatin B. II. Optically active piperidine derivatives having trifluoroacetamide and hydroxyacetamide groups at C-2.

Siastatin B analogues, optically active 2-(trifluoroacetamide)- 3,4,5-trihydroxypiperidines having nitromethyl, aminomethyl and carboxyl branched groups at C-5, and (+)-(2R,3R,4R,5R)-5-(aminomethyl)-3,4,5-trihydroxy-2- (hydroxyacetamido)piperidine have been obtained total synthetically from D-ribono-1,4-lactone. Some analogues have inhibitory activity against some glycosidases, and (+)-(2R,3R,4R,5R)-2-(trifluoroacetamido)-3,4,5-trihydroxypiperi dine-5-carboxylic acid showed a marked inhibitory activity against beta-glucuronidase.

Anti-Bacterial Agents

Stability difference between DNA and RNA mini-hairpins containing two G-C pairs.

The deoxyribonucleotide fragments, d(GCGAAAGC) and d(GCGAAGC) form extraordinarily stable mini-hairpin structures containing only two G-C pairs. In contrast, the corresponding ribonucleotide fragments, r(GCGAAAGC) and r(GCGAAGC) are not so stable, although they also form mini-hairpin structures. The stability difference between these DNA and RNA mini-hairpins was examined by NMR studies and the molecular mechanics calculations, and by comparing with the stability of several sequence variants. Their stability was deduced to vary delicately depending on helical patterns formed by DNA (B form) and RNA (A form) structures.

Base Composition

[A case of primary alveolar hypoventilation syndrome with a good response to nocturnal low-flow oxygen inhalation and negative pressure ventilation].

A 34-year-old female was admitted on June 25, 1990, for the evaluation of alveolar hypoventilation which worsened after her second delivery. She showed impairment of both hypercapnic and hypoxic ventilatory responses, and marked desaturation due to hypopnea and apnea during sleep. Although administration of methylxanthine and medroxyprogesterone was not very effective, after treatment with low flow oxygen, there was a marked decrease in the frequency and duration of desaturation during sleep and improvement of arterial daytime blood gases, which suggested the existence of hypoxic ventilatory depression in the pathophysiology of her nocturnal desaturation. Furthermore, the use of a negative pressure ventilator for 3 hours in the daytime for 10 days resulted in marked improvement of symptoms, arterial blood gases, respiratory muscle strength, and the frequency and duration of sleep desaturation. These findings suggest that both low flow oxygen therapy during sleep, and daytime negative pressure ventilation may be beneficial in patients with primary alveolar hypoventilation and central sleep apnea syndrome.

Adult

Interaction of a protooncogene product, Myb with DNAs.

The DNA-binding domain of Myb consists of three imperfect tandem repeats and the third one which is essential for sequence-specific binding was established to have a helix-turn-helix-related motif. DNA sequences recognized by Myb have been reported to contain TAACPy sequence. Here we have examined the details of Myb-binding sequence. Using DNAs with a single mutation on the various sites of two specific DNAs and some fragments of the DNA-binding domain of Myb, we have found that (i) in a specific DNA which contains only one AAC sequence, each AAC nucleotide is found to be essential for the specific binding of Myb, while any other mutations cause no serious binding loss, (ii) in a specific DNA which contains two AAC sequences separately, one AAC is not so important in the binding, and (iii) for the specific binding with DNA, at least both repeats 2 and 3 of Myb are required. These findings suggest that repeat 3 containing a helix-turn-helix-related structure recognizes the core AAC sequence and repeat 2 supports this recognition by interactions with phosphate groups of DNA.

Base Sequence

[Surgical treatment of brain stem lesions with reference to cavernous angioma].

The surgical indications for localized brain stem lesions were evaluated retrospectively through the clinical results of 14 patients: 5 cavernous angiomas and 9 gliomas. Cavernous angiomas were located in fourth ventricle floor (2 cases), in dorsal midbrain (1 case), in right cerebellar peduncle (1 case), and in medulla oblongata (1 case). Those cases had direct surgery because of relapse of clinical symptoms and enlargement of the lesions on follow-up MR imagings. Each lesion was extirpated totally. Consequently, the majority of neurological deficits before operation improved. Therefore, radical extirpation in brain stem cavernous angioma was strongly recommended. Also, total, subtotal resection was performed for gliomas localized in brain stem: 2 low grade astrocytomas, 3 malignant astrocytomas, 3 plexus papillomas, and 1 ependymoma. Most of cases improved without new neurological deficits after surgery. In addition, MR imaging was considered to be essential to accurate diagnosis and surgical strategies for brain stem lesions.

Adolescent

[Blood flow dynamics and dimensions of the descending thoracic aorta in patients with intra-aortic swirling echoes: assessment by biplane transesophageal echocardiography].

To examine the blood flow dynamics in the descending thoracic aorta (DAo) where intra-aortic swirling echo contrast was observed, we analyzed the flow velocity patterns (FVP) in DAo and the DAo dimensions by biplane transesophageal echocardiography (TEE) in 9 patients with intraortic swirling echo contrast and in 25 control subjects (N). We recorded sampling volumes with pulsed Doppler echocardiograms at 3 sites: median, central, and lateral sites on longitudinal scan images and on the DAo at the level of the mitral valve. We measured systolic peak flow velocity (Vp), time from the onset of the systolic flow to Vp (acceleration time: AT), deceleration time (DT) of the systolic flow, and AT/(AT + DT) for each sampling volume in the DAo. From the M-mode echogram of DAo, we measured the maximum dimension of the aorta, which usually coincided with the mid to late systolic phase. In the normal controls, the systolic forward flow was followed by a small reversal flow in early diastole and then by a small forward flow during holodiastole. Vp was highest at the center (64 +/- 10 cm/sec), then at the median (60 +/- 11 cm/sec) and lowest in the lateral (56 +/- 9 cm/sec; p < 0.01 vs center) sites in the DAo. AT was 70 +/- 13 msec and DT 215 +/- 26 msec. This flow velocity profile in the DAo was observed in both the control and patient groups. In patients with intra-aortic swirling echoes, Vp was markedly low (33 +/- 7 cm/sec; p < 0.001 vs N) and dimension of the DAo (13 +/- 2 mm/m2 in N) was significantly enlarged (21 +/- 7 mm/m2; p < 0.001 vs N), which might be related to swirling echoes and mural thrombi at the lateral portion in the DAo. Thus, we concluded that intra-aortic swirling echoes closely related to the production of mural thrombi observed mainly at the lateral site of the significantly dilated DAo.

Aged

[A case report of left upper lobectomy for lung cancer performed on an aged man of 90 year old].

A 90-year-old man was admitted to our hospital because of the dyspnea on exertion and an abnormal shadow of the chest. The examinations revealed pulmonary adenocarcinoma (bronchioloalveolar cell type) of the left S3 with clinical classification of stage I. Spirometry showed severe obstructive lung dysfunction (VC 2.05 l, % VC 75.2%, FEV1.0 0.72 l, FEV1.0% 39.3%). Walking exercise in the ward and the stairs as well as instrumental physiotherapy (Triflow) partially improved his respiratory function. Left upper lobectomy and lymphnode dissection were performed. On the 3rd postoperative day the patient developed mild delirium which disappeared in a few days. He was discharged from the hospital 62 days after the operation.

Adenocarcinoma, Bronchiolo-Alveolar

[Usefulness of segmental Lp-TAE using lipiodol mixed with anticancer agent for inoperable hepatocellular carcinoma].

To determine the effect of appraising subsegmental or segmental transarterial embolization with Lipiodol mixed with anticancer drugs followed by gelatin particles (Segmental Lp-TAE) on inoperable hepatocellular carcinoma, we examined CT patterns and therapeutic results in 57 patients after Segmental Lp-TAE. Fifty-six tumors including 47 tumors less than 5 cm in size were the nodular type and 1 tumor was the massive type. The mean tumor size was 3.6 cm and the mean amount of Lipiodol was 4.4 ml. Portal veins in the embolized segment were highly visualized by injected Lipiodol on plain film immediately after Segmental Lp-TAE. On the follow-up CT, the size of the tumor with dense Lipiodol accumulation were reduced in all cases, and atrophy of the embolized segment was recognized. Forty-four of the 57 patients are alive, with the longest surviving patient still alive at 4 years and 5 months. Seventeen patients have survived for more than 2 years (direct crude survival rate: 65.0%), with the cumulative survival rates 93.2% at 1 year, 71.6% at 2 years. No recurrence was recognized in 33 of the 41 patients (80.0%) that were followed up for more than 1 year after Segmental Lp-TAE is a useful therapeutic method for hepatocellular carcinoma.

Aged