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Biomedical subjects

Y Muraoka

Publications and source records attributed to Y Muraoka.

At least 19 recordsLinked to original sources

One-year prognosis of depressive illness in the elderly population in Japan.

A 1-year prospective study of 43 elderly depressed residents (13 men and 30 women) in Nagai City in Japan is described. An initial survey was carried out in 1993 to find depressed residents. The subjects of the survey were 2056 residents of 65 years of age and older. The Japanese version of the Geriatric Depression Scale (GDS) was employed as a screening tool in the first phase of the survey. In the second phase, screened subjects and control subjects were interviewed by psychiatrists using the Structured Interview for DSM-III-R (SCID). The diagnosis of depression was made by the psychiatrists on the basis of the results of the SCID. Forty-three persons were judged to be depressed. At follow-up, 10 were still depressed and 15 were well. Four were demented. Fourteen dropped out due to death, hospitalization, absence from home or refusal. The results showed that approximately half of the elderly depressed persons seemed to recover by the time of the 1-year follow-up. One-year prognosis of dysthymia was the worst. Some types of depression seemed to be a precursor for dementia. The concern is with how the findings may be used as an aid in understanding and planning community mental health services strategies. The results indicate that it is very important to pay close attention to patients with depressive illness who do not meet the criteria for major depression.

Aged

Induction of apoptosis in human pancreatic carcinoma cells by a synthetic bleomycin-like ligand.

Histidine-pyridine-histidine-3 (HPH-3) is an oxygen-activating ligand based on the structure of bleomycin. HPH-3 induced the death of human pancreatic adenocarcinoma AsPC-1 cells in 24 h, causing apoptotic morphology and internucleosomal degradation of DNA. HPH-3-induced cell death was not inhibited by antioxidants such as reduced glutathione and N-acetylcysteine, whereas hydrogen peroxide-induced cell death was inhibited by them, indicating that hydrogen peroxide is not involved in the induction of apoptosis by HPH-3. Induction of apoptosis by HPH-3 was inhibited by zinc and copper ions, indicating that chelation with ferrous ion is responsible for induction of apoptosis, as is the case in chelation by bleomycin to cleave DNA. Bleomycin A2 and its fragment having no DNA-binding region, glycopeptide-3, did not induce apoptosis in AsPC-1 cells. Bleomycin A2 induced G2/M block in flow-cytometric analysis, but HPH-3 did not and instead induced an apoptotic pre-G1 peak. Thus, HPH-3 induced apoptosis in human pancreatic carcinoma cells, which is a unique characteristic among bleomycin-related compounds.

Adenocarcinoma

Ovarian endometrioid adenocarcinoma coexistent with benign and borderline endometrioid adenofibroma: a case report.

A well-differentiated endometrioid adenocarcinoma coexistent with benign and borderline-malignant endometrioid adenofibroma was found in the ovary of a 64-year-old woman. She had vaginal bleeding caused by simple hyperplasia of the endometrium due to high levels of sex steroid hormones. A FIGO stage Ia solid ovarian tumor was identified. It was composed of irregularly shaped endometriotic glands with benign and borderline malignant cytologic features embedded in abundant fibromatous stroma. Well-differentiated malignant epithelium was adjacent to these areas, but fibromatous stroma was not predominant. She was treated by surgery and three cycles of chemotherapy. This paper describes this unusual tumor and reviews the literature.

Adenofibroma

Dependency on atrial electrophysiological properties of appearance of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome: evidence from atrial vulnerability before and after radiofrequency catheter ablation and surgical cryoablation.

The pathogenesis of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome and the effects of elimination of accessory pathways on the appearance of atrial fibrillation are still controversial. Fifty-four patients with Wolff-Parkinson-White syndrome were classified into three groups: a No AF group (n = 24), patients without paroxysmal atrial fibrillation; an RF-AF Group (n = 12), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated using radiofrequency catheter ablation; and a Cryo-AF Group (n = 18), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated with surgical cryoablation. The electrophysiological characteristics of each group were evaluated prior to and following the elimination of their accessory pathways. As indices of atrial vulnerability, the presence of fragmented atrial activity and repetitive atrial firing zones were assessed. Inducibility of atrial fibrillation was significantly reduced following ablation of accessory pathways in the Cryo-AF group (83.3%-5.6%, P < 0.0001), while it was unchanged in the RF-AF group (83.3%-75%). In preablation studies, the effective refractory periods of the atrium in the RF-AF group and the Cryo-AF group were significantly shorter compared with the No AF group (204 +/- 18 ms, 197 +/- 16 ms vs 246 +/- 44 ms, respectively, P < 0.0001). Following ablation, the effective refractory period for patients in the Cryo-AF group was significantly prolonged compared with before ablation (197 +/- 16 ms to 232 +/- 24 ms, P < 0.0001). As a result of this prolongation of the effective refractory period of the atrium, the fragmented atrial activity and repetitive atrial response zones narrowed following ablation in the Cryo-AF group, but not in the RF-AF group. Therefore, the pathogenesis of atrial fibrillation in patients with Wolff-Parkinson-White syndrome may depend on the refractory period of the atrium rather than on the presence of accessory pathways.

Adult

[Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats].

Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day.

Animals

Epostatin, new inhibitor of dipeptidyl peptidase II, produced by Streptomyces sp. MJ995-OF5. I. Taxonomy of producing strain, fermentation, isolation, physico-chemical properties and biological properties.

A new inhibitor of dipeptidyl peptidase II (DPP-II, EC 3.4.14.2), designated as epostatin, was discovered in the fermentation broth of a strain isolated in our institute. The strain has been identified as Streptomyces sp. MJ995-OF5 on the basis of taxonomic studies. Epostatin was obtained as a yellow powder after seqential purification by chromatography on Diaion HP-20, n-butanol extraction, Sephadex LH-20 column chromatography and centrifugal partition chromatography (CPC). Epostatin inhibited DPP-II competitively in a dose dependent manner. The compound was slightly inhibitory against other dipeptidyl peptidases.

Alanine

Fluostatins A and B, new inhibitors of dipeptidyl peptidase III, produced by Streptomyces sp. TA-3391. I. Taxonomy of producing strain, production, isolation, physico-chemical properties and biological properties.

New inhibitors of dipeptidyl peptidaseIII (EC 3.4.14.4) from human placenta, designated as fluostatins A and B, were discovered in the fermentation broth of a strain isolated in our institute. The strain has been identified as Streptomyces sp. TA-3391 on the basis of taxonomic studies. Fluostatins A and B were purified by Diaion HP-20 chromatography, ethyl acetate extraction, silica gel chromatography and reverse phase preparative HPLC. With the synthetic substrate, arginyl-arginine-2-naphthylamide, the IC50 values of fluostatins A and B were 0.44 and 24.0 micrograms/ml, respectively. Fluostatins A and B were slightly inhibitory against other dipeptidyl peptidases. Fluostatin A showed mixed-type (competitive and noncompeptitive) inhibition with human leucine-enkephalin as a substrate, and the inhibition constant (Ki) was 14.2 microM.

Chromatography, High Pressure Liquid

One-point measurement of the peak-to-peak pulsatility index as an indicator for evaluation of infrainguinal bypass procedures.

While duplex scanning has been advocated as the most accurate modality for postoperative graft surveillance, it is time-consuming for evaluating the entire graft. The aim of the present study was to determine which parameter predicts graft failure most simply and precisely, by examining 62 men and 1 woman who collectively underwent 71 infrainguinal arterial bypasses. A total of 212 scannings were obtained using a duplex scanner, and the peak systolic velocity (PSV), PSV ratio, and peak-to-peak pulsatility index (PPI) were analyzed. This analysis revealed 7 occlusions, 9 stenoses, and 1 arteriovenous fistula. When a PSV < 45 cm/s and/or a PSV ratio > 2.0 was defined as graft failure the sensitivity was 84.0% and the specificity was 81.8%: however, a PPI < 7.0 at the midgraft, indicating graft failure, showed a sensitivity of 100% and a specificity of 83.3%. The PPI exhibited better sensitivity and specificity than the PSV, even though the PPI needs only to be measured at the midgraft whereas the PSV should be measured at at least two points. Thus, we believe that the PPI could be the most useful and simple parameter to assess infrainguinal bypass grafts.

Adult

Isolation and synthesis of novel farnesyl protein transferase inhibitors, valinoctins A and B, from Streptomyces strain MJ858-NF3.

Two novel farnesyl protein transferase inhibitors, valinoctins A (1) and B (2), were isolated from the fermentation broth of Streptomyces strain MJ858-NF3. The tentative structures of these compounds were elucidated from NMR and mass spectra as dipeptides consisting of valine and a novel amino acyl moiety. Four possible isomers of valinoctin A were synthesized, and the protected derivative of the appropriate compound was crystallized to give the relative stereochemistry of X-ray analysis. Since the valine residue of valinoctin A was determined to be the L-configuration by a chiral HPLC column, absolute configuration of valinoctin A was determined.

Animals

Poststatin, a new inhibitor of prolyl endopeptidase. VIII. Endopeptidase inhibitory activity of non-peptidyl poststatin analogues.

Non-peptidyl postatin analogues, (S)-N-substituted-2-[2-(1-acylpyrrolidinyl)]-2-oxoacetamides were synthesized and examined for their inhibitory activity against prolyl endopeptidase and cathepsin B in vitro. Many compounds showed stronger activity than natural poststatin, a pentapeptide. Among them, (S)-N-cyclohexyl-2-oxo-2-[2-(1-(3-phenoxybenzoyl)pyrrolidinyl)]ace tamide (22) and (S)-N-cyclohexyl-2-[2-(1-(2-naphthoyl)pyrrolidinyl)]-2-oxoacetamide++ + (19) indicated IC50 value of 5.8 and 8.2 ng/ml for prolyl endopeptidase inhibition respectively. None of these compounds possess significant inhibitory activities against cathepsin B, a cysteine protease. These results indicate that these compounds are more selective inhibitors against prolyl endopeptidase than is natural poststatin.

Magnetic Resonance Spectroscopy

Stereospecific synthesis of a novel farnesyl protein transferase inhibitor, valinoctin A and its analogues.

(2S,3R)-3-Amino-2-hydroxyoctanoic acid was synthesized by Curtius rearrangement of an azide derivative of (S)-malic acid. Total syntheses of valinoctin A and its analogues were achieved by a coupling of (2S, 3R)-3-amino-2-hydroxyoctanoic acid moiety with L-valine or several other amino acids moieties. 2S configuration of 3-amino-2-hydroxyoctanoic acid moiety was found to be important for the inhibitory activity and the L-valine moiety of valinoctin A was exchangeable with other L-amino acids.

Alkyl and Aryl Transferases

Poststatin, a new inhibitor of prolyl endopeptidase. III. Optical resolution of 3-amino-2-hydroxyvaleric acid and absolute configuration of poststatin.

3-Amino-2-hydroxyvaleric acid was prepared, and separated into its diastereomers. The relative stereochemistry was determined by 1H NMR in their oxazolidone derivatives. The threo-isomer was resolved by (S)-1-(1-naphthyl) ethylamine in the N-(p-methoxybenzyloxycarbonyl) derivative. The absolute configuration of (--)-threo-3-(p-methoxybenzyloxycarbonyl)amino-2-hydroxyvaleric acid was confirmed to be 2R, 3S. The absolute configuration of 3-amino-2- oxovaleric acid in poststatin was confirmed to be S by comparison of the four stereoisomers of methyl N, O-bis(3,5-dinitrobenzoyl)-3-amino-2-hydroxyvalerate derived from 3-amino-2-hydroxyvaleric acid and that derived from 3-amino-2-oxovaleryl moiety of poststatin by means of HPLC with chiral column.

Amino Acid Sequence

Poststatin, a new inhibitor of prolyl endopeptidase. IV. The chemical synthesis of poststain.

Total synthesis of poststatin was achieved by both liquid phase and solid phase methods. In both methods, the (2R,3S)-3-amino-2-hydroxyvaleric acid moiety was incorporated into protected pentapeptides, and was oxidized to (S)-3-amino-2-oxovaleric acid (postine). Deprotection of the oxidized pentapeptides gave a specimen identical with natural poststatin in physico-chemical properties and prolyl endopeptidase inhibitory activity.

Amino Acid Sequence

Poststatin, a new inhibitor of prolyl endopeptidase. V. Endopeptidase inhibitory activity of poststatin analogues.

Thirty analogues of poststatin were synthesized, and their inhibitory activities against prolyl endopeptidase, human leukocyte elastase and cathepsin B were measured. The alpha-ketone was essential and the S configuration was preferable to the R configuration in the beta-substituted-beta-amino-alpha-oxopropionic acid moiety of poststatin analogues for endopeptidase inhibitory activity. The analogue in which the D-leucine residue of poststatin was replaced by L-leucine showed strong inhibitory activity to cathepsin B. Introduction of an aromatic group into the P4 position and proline into the P2 position increased inhibitory activity to elastase. Benzyloxycarbonyl-L-homophenylalanyl-(RS)- 3-amino-2-oxovaleryl-D-leucyl-L-valine was about 6 times more active to prolyl endopeptidase than natural poststatin.

Cathepsin B

Poststatin, a new inhibitor of prolyl endopeptidase. VI. Endopeptidase inhibitory activity of poststatin analogues containing pyrrolidine ring.

Several pyrrolidine-containing analogues of poststatin were synthesized and examined for their inhibitory activity against prolyl endopeptidase and cathepsin B in vitro. Replacement of the postine residue with 2-oxo-2-(2-pyrrolidinyl)acetic acid increased the selectivity and inhibitory activity against prolyl endopeptidase. Benzyloxycarbonyl-L-phenylalanyl-(S)-2-oxo-2- (2-pyrrolidinyl)acetyl-D-phenylalanine was about 46 times as active to propyl endopeptidase as natural poststatin.

Cathepsin B