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Biomedical subjects

S Yamaguchi

Publications and source records attributed to S Yamaguchi.

At least 883 records · Page 49Linked to original sources

Effects of an antithrombotic agent (MD-805) on progressing cerebral thrombosis.

The effects of the newly developed synthetic selective antithrombin agent MD-805 were examined in 11 patients with progressing cerebral thrombosis, as an open trial. Nine (82%) of 11 patients improved after 1 week of intravenous drip infusion. No hemorrhagic complications were observed during the therapy. These results suggest that MD-805 is a safe and effective agent for treatment of progressing cerebral thrombosis.

Aged↗

Human scalp hair as evidence of individual dosage history of haloperidol: method and retrospective study.

Hair samples and morning pre-dose plasma were collected from 40 patients who had received fixed daily doses of haloperidol for more than four months and whose compliance was good. After washing, 1 to 2 cm-long portions nearest to the roots of 2 to 3 strands of hair were completely dissolved in 2.5N NaOH. Haloperidol in that sample or alkalinised plasma was extracted and measured by RIA. Haloperidol concentrations in hair correlated well both with the trough concentration in plasma at steady-state (r = 0.772, n = 39) and with the daily dose (r = 0.555, n = 40). Another keratinized tissue, nail, was also collected from 20 of the 40 patients and the haloperidol level was compared with that in hair. The former was only about 4.3% of the latter and was significantly correlated only with the daily dose (r = 0.525, n = 20). Hair from 10 other patients in whom the dosage of haloperidol had been changed within a few months prior to sampling the hair was cut into 0.5 or 1 cm-long portions from the roots and the drug concentration in each portion was measured. If hairs were assumed to grow at 1 cm/month, a history of individual dosage could be deduced in 9 of the 10 patients from the distribution of drug level along the length of the hair. The results suggest that human scalp hair could serve as a useful tool for monitoring individual dosage history over several months, or in demonstrating exposure or non-exposure of a patient to a drug.

Adult↗

Adrenal myelolipoma discovered incidentally on abdominal CT and MR imaging.

This report describes an adrenal myelolipoma occurring in a 39-year-old man first noted incidentally by computed tomography (CT). The radiographic findings of this neoplasm are briefly discussed and magnetic resonance (MR) imaging of myelolipoma is also described. Myelolipomas can be distinguished from nonfunctioning adenomas by differences in signal intensity on T2-weighted images.

Adrenal Gland Neoplasms↗

Pial arterial pressure contribution to early ischemic brain edema.

The effect of pial arterial pressure (PAP) on brain edema was examined in cats with middle cerebral artery (MCA) occlusion. Measurements of PAP and regional CBF (rCBF) were collected in the central core and the peripheral margin of the MCA territory over 180 min post MCA occlusion. Brain water content in each region was determined at the end of the experiment. MCA occlusion resulted in decreased PAP and rCBF in both the core (PAP = 13 mm Hg, rCBF = 9 ml/100 g/min) and the peripheral region (PAP = 15 mm Hg, rCBF = 18 ml/100 g/min). Brain edema developed in both the core and the peripheral region. Brain water content was correlated inversely with PAP in the core region and positively in the peripheral region. The results indicate that decreased blood flow contributes to cytotoxic edema in the core, and a hydrostatic pressure gradient preferentially enhances edema formation in the peripheral region. Maintenance of high perfusion pressure early after ischemia onset may suppress brain edema in the core region.

Animals↗

Molecular cloning and nucleotide sequence of cDNA encoding the entire precursor of rat mitochondrial acetoacetyl-CoA thiolase.

cDNA clones for rat mitochondrial acetoacetyl-CoA thiolase were isolated and sequenced. The most 5'-extended clone (RT2-6) consisted of 1,460 bases and contained a 1,272-base open reading frame encoding a polypeptide of 424 amino acid residues. A coupled in vitro transcription/translation analysis of RT2-6 revealed that RT2-6 encodes the entire precursor of this enzyme. The amino-terminal sequence and amino acid composition of the purified enzyme agreed with the primary structure deduced from the cDNA. The calculated molecular masses of the precursor and the subunit of the mature enzyme are 44,694 and 41,364 Da, respectively. The primary structure of this enzyme was compared with those of four other thiolases (rat mitochondrial and peroxisomal 3-ketoacyl-CoA thiolases, acetoacetyl-CoA thiolase of Zoogloea ramigera, and cytosolic acetoacetyl-CoA thiolase of Saccharomyces uvarum). Marked homology between any two of them (34-51% identity) indicates that the genes of thiolases have evolved from a common ancestral gene. It has been reported that this enzyme has two isoenzymes A and B. However, the purified isoenzymes were indistinguishable from each other in some analyses. Though 17 independent cDNA clones were isolated, no definite evidence indicating the presence of different cDNAs was found.

Acetyl-CoA C-Acetyltransferase↗

Human scalp hair as evidence of individual dosage history of haloperidol: prospective study.

The concentration of haloperidol in hair was measured by radioimmunoassay after hairs were dissolved in 2.5 N NaOH solution and the drug was extracted. In patients to whom haloperidol had been administered at fixed daily doses for more than 1 month, and in whom therapy had been just discontinued (group A, n = 5) or the doses cut to half (group B, n = 3), hairs were collected when the dose was changed and at 1 and 2 or 3 months thereafter. A few strands of hair collected on each occasion were cut into 1-cm-long portions from the roots, and the haloperidol concentration was measured in each portion. When hairs were assumed to grow at a rate of 1-1.5 cm/month, the portion of hair that reflected the change of dose was observed to move upward along the hair length in all patients of group A. However, these phenomena were less obvious in group B. These results indicate that at the least, hair could serve as an indicator of individual exposure or nonexposure to haloperidol and could yield retrospective information. In rats whose hairs had been removed by plucking from an area on the back, either saline or 1 mg/kg of haloperidol (i.p., b.i.d.) was administered for 2 weeks (first period), followed by 0, 0.5, 1, or 2 mg/kg b.i.d. for the subsequent 2 weeks (second period). At the end of each period, hairs that had grown in the plucked area were collected. Within-groups, haloperidol levels in hairs collected at the end of each period corresponded to the doses given.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Completion of the sequence of bluetongue virus serotype 10 by the characterization of a structural protein, VP6, and a non-structural protein, NS2.

The sequence of cDNA clones representing the entire genome of bluetongue virus serotype 10 (BTV-10) has been completed by the analysis of data obtained for the S8 and S9 segments. Each DNA clone has been sequenced completely and the deduced amino acid sequences have been analysed. The sequences of the S8 and S9 gene products as well as another two previously published small gene products (S7 and S10) have been compared with the corresponding size gene products of reovirus type 1. The data do not indicate a relationship between the small proteins of these two viruses except some distant homologies between the BTV VP7 protein and the sigma 1 protein of reovirus. The characteristics of all the BTV-10 genome segments, the deduced primary gene products and their possible functions are summarized.

Amino Acid Sequence↗

Co-amplification of c-myc and c-erbB-2 oncogenes in a poorly differentiated human gastric cancer.

c-erbB-2 oncogene has been reported to be frequently amplified in differentiated, tubular type of gastric cancer. Here we report a human gastric cancer which bore co-amplified c-myc and c-erbB-2 oncogenes: a portion of the amplified c-erbB-2 oncogene was found to be rearranged. Furthermore, c-myc and c-erbB-2 oncogenes were over-expressed in the tumor cells. In contrast to the previous reports, this gastric adenocarcinoma was classified as a poorly differentiated type, and was highly tumorigenic in nude mice. These results might suggest that activated c-myc and c-erbB-2 oncogenes co-operate and influence the malignant state of some gastric carcinomas.

Adenocarcinoma↗

Synergistic effects of low-dose hepatocarcinogens in induction of glutathione S-transferase P-positive foci in the rat liver.

The effects of combined administration of hepatocarcinogens at low doses on the development of glutathione S-transferase P-form (GST-P)-positive foci of rat liver were examined utilizing a bioassay model which consists of a single injection of diethylnitrosamine (DEN, 200 mg/kg, ip), two-thirds partial hepatectomy at week 3 and a 6-week administration of test compounds. The chemicals used, 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), phenobarbital (PB), thioacetamide (TAA), N-ethyl-N-hydroxyethylnitrosamine (EHEN), benzo[a]pyrene (B[a]P), carbazole, and alpha-hexachlorocyclohexane (alpha-HCH) were incorporated in the diet, except for EHEN which was dissolved in the drinking water, at levels of 1/6 of the doses usually used. The combinations were: I) 2-AAF, 3'-Me-DAB, PB, TAA, EHEN and B[a]P, II) 2-AAF, 3'-Me-DAB and PB, III) TAA, EHEN and B[a]P, IV) 2-AAF, 3'-Me-DAB, carbazole, TAA, EHEN and alpha-HCH, V) 2-AAF, 3'-Me-DAB and carbazole, and VI) TAA, EHEN and alpha-HCH. All combinations, except for II, caused an increase in the area of the foci as evaluated by the ratios of areas in the combined administration groups to the sum totals of 3 or 6 individual data: I) 1.75, II) 0.81, III) 2.01, IV) 3.62, V) 1.34 and VI) 2.91. The non-synergistic effect in combination II might be related to PB induction of hepatic microsomal enzymes leading to enhanced enzymatical detoxification of 2-AAF and 3'-Me-DAB. The present results indicate that exposure to several chemicals of similar organotropism, even at doses lower than the apparent carcinogenic levels, might be critical to the carcinogenic process.

2-Acetylaminofluorene↗

Release of flagellar filament-hook-rod complex by a Salmonella typhimurium mutant defective in the M ring of the basal body.

A Salmonella typhimurium strain possessing a mutation in the fliF gene (coding for the component protein of the M ring of the flagellar basal body) swarmed poorly on a semisolid plate. However, cells grown in liquid medium swam normally and did not show any differences from wild-type cells in terms of swimming speed or tumbling frequency. When mutant cells were grown in a viscous medium, detached bundles of flagellar filaments as long as 100 microns were formed and the cells had impaired motility. Electron microscopy and immunoelectron microscopy revealed that the filaments released from the cells had the hook and a part of the rod of the flagellar basal body still attached. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis showed that the rod portion of the released structures consisted of the 30-kilodalton FlgG protein. Double mutants containing this fliF mutation and various che mutations were constructed, and their behavior in viscous media was analyzed. When the flagellar rotation of the mutants was strongly biased to either a counterclockwise or a clockwise direction, detached bundles were not formed. The formation of large bundles was most extreme in mutants weakly biased to clockwise rotation.

Bacterial Proteins↗

Risk factors in chronic obstructive pulmonary malfunction and "chronic bronchitis" symptoms in Beijing district: a joint study between Japan and China.

A cross sectional study of risk factors in respiratory diseases was carried out in August 1986, in Beijing, China. Inhabitants greater than or equal to 40 years old were selected at random from a rural area, a residential area and an industrial area, using a two stage sampling method. The analysis presented here is based on the sample population of adults who (1) were prepared to be interviewed, using the British Medical Research Council's questionnaire translated into Chinese (n = 3423) and (2) had lung function measurements at the same time (n = 3373). Obstructive lung disease was defined as forced expiratory volume in 1s (FEV1) less than 68% of forced vital capacity (FVC). Seven variables were considered as potential risk factors or confounding factors: area of residence, sex, age, cigarette smoking, history of respiratory disease, socio-economic status and familial component. A modified binary variable regression method developed by Feldstein was used for the adjustment of rate ratios. The adjusted prevalence of obstructive lung disease was highest in the rural area and lowest in the residential area(s). An increase in age, cigarette smoking, low socio-economic status and positive history of respiratory diseases were associated with significantly higher rates of impaired pulmonary function. The other measured factors did not appear to be related to impaired pulmonary function.

Adult↗

Changes in the uterus and vagina of mice treated neonatally with antiestrogens.

Adenosis-like lesions (ADL) were found in the upper vagina including the cervical region of ICR mice as early as 1 day after 5 daily injections of 200 micrograms tamoxifen (Tx) starting on the day of birth (200-micrograms Tx mice). ADL developed progressively from 5 to 30 days of age. Involution of the musculature and suppression of the gland genesis occurred in the uterus of 5- to 30-day-old, 200-micrograms Tx mice. The uterine abnormality resulted in a loss of type III collagen and laminin, and in an increase in fibronectin and type I collagen in the mesenchymal stroma of 15-day-old, 200-microgram Tx mice. Vaginal ADL and uterine myometrial involution were also encountered in 35-day-old mice given neonatal injections of 2-200 micrograms Tx, 200 micrograms clomiphene (Clm) and 200 micrograms nafoxidine (Naf), respectively. These changes were never observed in control and 0.2-microgram Tx mice. Ovariectomy performed at 10 days resulted in a reduction in the weight of uteri and the extent of ADL occupancy in Tx, Clm and Naf mice. Five daily injections of 0.1 microgram 17 beta-estradiol (E2) beginning at 30 days of age increased uterine weight and ADL occupancy extent in Tx (2-200 micrograms), Clm and Naf mice. The present findings suggest, therefore, that the antiestrogens act as an estrogen agonist to mouse uterus and vagina and that the induced ADL develops progressively depending on ovarian estrogen.

Animals↗

Correlation between carotid blood flow and brain atrophy in patients with multi-infarct dementia.

The relation between carotid blood flow measured by Doppler spectrum analysis and brain atrophy on computed tomography (CT) was studied in 22 subjects with multiple lacunar cerebral infarctions. The subjects were divided into two groups, 7 patients with multi-infarct dementia (MID) (mean age 73 years) and 15 nondemented lacunar stroke subjects (NDLS) (mean age 66 years), according to DSM III criteria. All subjects had a score of 7 points or more on Hachinski's ischemic score and showed no carotid artery stenosis. Systolic peak frequency of the common carotid artery (CCA) was measured by Doppler spectrum analysis (Angioscan II). Brain atrophy was measured quantitatively on CT images by two-dimensional measurement using a digitizer. Peak frequencies were lower in MID than in NDLS. Brain atrophy was more severe in MID than in NDLS. There was a significant correlation between peak frequencies and brain atrophy in all subjects. These results indicate that CCA blood flow may reflect brain function in patients with multiple lacunar infarctions.

Aged↗

Effect of left ventricular volume on right ventricular end-systolic pressure-volume relation. Resetting of regional preload in right ventricular free wall.

Effect of left ventricular (LV) volume on right ventricular (RV) end-systolic pressure-volume relation (ESPVR) was investigated, and the mechanism was examined from a standpoint of the alteration of RV free wall mean fiber length. Twelve cross-circulated isovolumically contracting canine hearts in which both ventricular volumes were controlled independently were used, and RV-ESPVR was determined at three different LV volume levels. At small (10.2 +/- 0.6 ml), middle (15.3 +/- 1.0 ml), and large (20.5 +/- 1.4 ml) LV volume, the slope of the RV-ESPVR was 2.63 +/- 0.13, 2.74 +/- 0.13, and 2.89 +/- 0.12 mm Hg/ml, respectively, and each value was significantly different from the others (p less than 0.01). The volume intercept (V0) of the relation (RV-V0) was significantly decreased with the increment of LV volume (RV-V0 in small, middle, and large LV volume; 3.92 +/- 0.68, 3.39 +/- 0.67, and 2.87 +/- 0.71 ml, respectively; p less than 0.01). In nine hearts, RV free wall lengths in latitudinal and meridional direction were measured at three LV volume levels when RV volume was held constant (16.1 +/- 1.1 ml). RV latitudinal end-diastolic length was significantly augmented with increasing LV volume (latitudinal length in small, middle, and large LV volume; 9.68 +/- 0.55, 9.81 +/- 0.56, and 9.92 +/- 0.55 mm, respectively). RV meridional end-diastolic length also increased significantly with increasing LV volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Heterogeneity of defects in mitochondrial acetoacetyl-CoA thiolase biosynthesis in fibroblasts from four patients with 3-ketothiolase deficiency.

Deficient mitochondrial acetoacetyl-CoA thiolase in fibroblasts from four patients with 3-ketothiolase deficiency was studied using immunochemical methods. We also examined fibroblasts from two heterozygotes, the mother and the brother of the case 1 patient, identified on the basis of the results of the enzyme activity measurements, using 2-methylacetoacetyl-CoA as substrate. The results were as follows: 1) in fibroblasts from all four patients, the thiolase activity using acetoacetyl-CoA was not activated by K+, although that of the controls and the heterozygotes was activated about 2-fold. 2) by immunoblot analyses, mitochondrial acetoacetyl-CoA thiolase was not detectable in fibroblasts from cases 2 and 3, although a very faint band was seen in tissues from cases 1 and 4. However, the band of mitochondrial 3-ketoacyl-CoA thiolase was clearly detected in all patients to the same extent as in the controls. 3) mitochondrial acetoacetyl-CoA thiolase was observed after pulse labeling for 1-h and a 72-h chase period in three cell lines (cases 1, 2, and 4), but was fainter compared to the controls. In another cell line (case 3), a fluorographic band at the same position was detected following a 1-h pulse, but disappeared following a 6-h chase. These results demonstrate heterogeneity in the enzyme defect resulting in a deficiency of mitochondrial acetoacetyl-CoA thiolase in fibroblasts from patients with 3-ketothiolase deficiency.

Acetyl-CoA C-Acetyltransferase↗