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Biomedical subjects

Y Shimada

Publications and source records attributed to Y Shimada.

At least 19 recordsLinked to original sources
PubMed1992

Tissue selectivity of pravastatin sodium, lovastatin and simvastatin. The relationship between inhibition of de novo sterol synthesis and active drug concentrations in the liver, spleen and testis in rat.

Tissue selectivity of pravastatin sodium (pravastatin), lovastatin and simvastatin, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors was examined by measuring inhibition of de novo sterol synthesis and active drug concentrations in the liver, spleen and testis in rats after a single oral administration (25 mg/kg) of these drugs. Regarding tissue drug concentrations, all three drugs were liver selective: concentrations of drugs in the liver were about ten-times higher than those in the spleen and testis. On the other hand, pravastatin was far more liver selective in inhibiting sterol synthesis than two other inhibitors: pravastatin inhibited de novo sterol synthesis in the liver but minimally in the spleen and testis, whereas lovastatin and simvastatin inhibited in all three tissues. Microautoradiographic and in vitro cellular-uptake studies demonstrated that pravastatin remained in the extracellular space in the spleen, whereas the other drugs entered the cell. We conclude that pravastatin exhibits a liver-selective inhibition of sterol synthesis because the agent permeates the cell membrane in the liver, but not in non-hepatic tissues.

Animals↗
PubMed1992

Oligo(2'-O-methyl)ribonucleotides. Effective probes for duplex DNA.

To find novel probes for duplex DNA, we prepared four types of triplexes containing a homopurine-homopyrimidine 15-mer duplex DNA, and examined their thermal stabilities (Tm values). The single strand used for triplex formation were a DNA 15-mer having a defined C-T mixed sequence, and its sugar-modified analogs, namely 2'-fluoro DNA, RNA, and 2'-O-methyl RNA. The 2'-O-methyl RNA and the RNA-containing triplexes were similar in their enhanced stabilities at pH 6.1 and, amongst the four triplexes, the 2'-O-methyl was the most stable at pH 5.0. Furthermore, an experiment using a 34-mer duplex DNA suggested that the 2'-O-methyl RNA-triplex was destabilized, mostly as a result of the incorporation of a mismatched triplet, as compared to the DNA triplex counterpart. Thus, 2'-O-methyl RNA can serve as an effective probe for duplex DNA.

Base Sequence↗
PubMed1992

Expression of the interleukin-3 and granulocyte-macrophage colony-stimulating factor genes in Friend spleen focus-forming virus-induced erythroleukemia.

Friend spleen focus-forming virus (F-SFFV) is a replication-defective retrovirus that induces a multistage erythroleukemia in mice. In the first stage, expression of the SFFV envelope glycoprotein results in erythroid hyperplasia. Subsequently, the F-SFFV integrates near the Spi-1 gene and activates its expression, resulting in immortalized cells that represent a second stage in the disease process. We report here that media conditioned by erythroleukemia cell lines or leukemic spleen cells induced by the polycythemia-inducing strain of F-SFFV (F-SFFVp), but not medium conditioned by SFFVp-induced hyperplastic spleens, promote the proliferation of normal granulocyte-macrophage progenitor cells and of granulocyte-macrophage colony-stimulating factor (GM-CSF)- and/or interleukin-3 (IL-3)-dependent cell lines. The colony-stimulating activity of the conditioned media from four of five of the lines studied was neutralized by antibodies specific for IL-3 and/or GM-CSF, and IL-3 and GM-CSF-specific mRNA could be detected in the cells after amplification by the polymerase chain reaction. No rearrangements of the IL-3 or GM-CSF genes were observed by Southern blot analysis. However, as previously shown for SFFV-induced cell lines, the Spi-1 gene was expressed in all of these cells. Because the Spi-1 gene encodes a transcription factor whose cognate sequences are present in the promoter region of many hematopoietic growth factor genes, including IL-3 and GM-CSF, Spi-1 activation may be inducing the expression of these genes.

Animals↗
PubMed1992

Extracellular pH modulates N-methyl-D-aspartate receptor-mediated neurotoxicity and calcium accumulation in rat cortical cultures.

The effect of extracellular pH (pHo) on the excitotoxicity of N-methyl-D-aspartate (NMDA) in cultured rat cortical cells was studied. Treatment of cells with 500 microM NMDA for 15 min at various pH's in a range from 6.5 to 8.0 progressively enhanced staining with Trypan blue and release of lactate dehydrogenase with increased pH after 18 h of culture following treatment. The cytotoxic effect of high concentration of K+ (40 mM) or veratridine (10 microM) was also directly related to the increase in pHo. Free calcium accumulation in cells on addition of NMDA increased parallel to pHo. Changes in intracellular pH were estimated to be minor compared with extracellular changes. Specific NMDA antagonists could block both the NMDA- and membrane depolarization-induced neurotoxicity and calcium accumulation completely. These results suggest that the proton concentration outside of cells attenuates NMDA-induced neurotoxicity by blocking calcium accumulation.

Animals↗
PubMed1992

Intercellular junctions in embryonic chick cardiac muscle revealed by rapid freezing and freeze-substitution.

Using the method of rapid freezing and freeze-substitution, the embryonic chick cardiac muscle was investigated by transmission electron microscopy. Initially, the intercellular junctional complexes (fasciae adherentes and desmosomes) were formed in close proximity to each other along a nearly straight line. Subsequently, the separation of fasciae from desmosomes took place to form intercalated discs. The cell membranes of fasciae adherentes were reinforced with highly interwoven fine fibrils at which myofibrils terminated. The intercellular space of fasciae was bridged with fine fibrillar structures seemingly connected by a thin line at their middle portions. In the intercellular space of desmosomes, central lamina and traversing filaments were clearly observed. The outer and inner leaflets of the desmosomal plasmalemma were asymmetrically differentiated; the outer leaflet was thinner than the inner leaflet. On the inner side of the cell membrane, an electron-lucent layer and a dense desmosomal plaque were observed. The latter structure had protrusions with less electron density towards the cytoplasmic side. Further inside, a meshwork of fine fibrils was seen along and toward which bundles of intermediate filaments ran. The results obtained with freeze-substitution appeared to provide more information than those with thin sections after conventional fixation or with replicas of chemically fixed/glycerinated or physically fixed/deep-etched materials.

Animals↗
PubMed1992

Characterization of 21 newly established esophageal cancer cell lines.

Twenty-one esophageal cancer cell lines (KYSE series) have been established from the resected specimens of patients with esophageal cancer. Three lines, KYSE-30, KYSE-50, and KYSE-70, were derived from the implanted tumor of nude mice (initial passage); others were derived from resected specimens. Each cell line was morphologically distinct. Detailed cytogenetic analysis indicated that each cell line was karyotypically unique, and DNA fingerprint analysis showed no cross-contamination among cells. Doubling time ranged from 13.7 to 75.5 hours, and modal chromosome numbers ranged from 46 to 120. Most cell lines grew in monolayer, but two cell lines (KYSE-50 and KYSE-360) grew as floating cell aggregates. No correlation was demonstrated between the establishment of cell lines and cell differentiation. These cell lines are the first reported to be homogeneous and individually unique and may provide a useful model for the study of human esophageal cancer.

Animals↗
PubMed1992

Usefulness of preoperative low dose cisplatin treatment for advanced esophageal cancer.

In order to decrease the perioperative complications by preoperative cisplatin chemotherapy, the preoperative single administration of cisplatin (30 mg/m2) was performed weekly from one to six times in 36 consecutive patients with esophageal cancer classified as higher than Stage II. The survival curve of 17 patients in Stage III was significantly better (P < 0.05) than that of patients who had been treated without preoperative cisplatin treatment. In 3 of the 12 patients who had locally invasive cancer, either the main tumors or the metastatic lymph nodes, which had invaded the trachea or the left main bronchus, sufficiently receded, so that a curative esophagectomy became possible; 2 of them have survived over 33 months while 1 died of pneumonia 33 months after surgery. The number of perioperative complications was minimal, and thus, we consider that the postoperative use of cisplatin and fluorouracil is indicated in patients in whom a histological response is noted in the resected specimens.

Aged↗
PubMed1992

Hemodynamic changes after resection of thoracic duct for en bloc resection of esophageal cancer.

An en bloc resection of esophageal cancer is one of the most radical forms of esophagectomy, and includes the resection of the thoracic duct, but a relatively high hospital mortality rate has been reported. There is very little knowledge on the pathophysiological changes after resection of the thoracic duct. We examined 24 patients who underwent en bloc resection. Some patients developed severe tachycardia or shock postoperatively which subsided after a massive infusion of plasma. Analysis of the fluid balance revealed that much more fluid was necessary during surgery and the postoperative 24 h than in patients treated by a standard esophagectomy. Postoperative lymphangiography or CT revealed abnormal collateral lymphatics around the kidneys or in the pelvic cavity. This suggests the development of the lymphaticovenous shunts, which differed depending on the anatomy of each patient. One patient with chronic hepatitis developed uncontrollable ascites. These are important findings which can hopefully reduce the high rate of hospital death after this operation.

Aged↗
PubMed1992

Multiple cis-acting DNA elements that regulate transcription of the adenovirus 12 E1A gene.

To delineate cis-acting elements for adenovirus (Ad) 12 E1A gene transcription, we transfected HeLa and NIH3T3 cells with DNAs having various deletions in the 5'-upstream region linked to the chloramphenicol acetyltransferase gene. Deletions in the regions between nucleotide (nt) positions 54 and 166, and 167 and 200, with respect to the left end of the viral genome at nt position 1, caused a two- to three-fold reduction in transcription. Transcription decreased to an almost undetectable level with loss of the region between nt positions 201 and 282. The effect of these mutations was almost consistent between both cell lines. The region between nt positions 77 and 94 stimulated transcription when situated upstream of the simian virus 40 early promoter in either orientation. Transcription was stimulated about ninefold in the presence of the DNA that encodes the product of the 13S, but not the 12S mRNA of the Ad12 E1A gene. These results indicate that transcription of the Ad12 E1A gene is regulated by multiple cis-acting elements and is stimulated by its own gene product.

3T3 Cells↗
PubMed1992

Spatial relationship of nebulin relative to other myofibrillar proteins during myogenesis in embryonic chick skeletal muscle cells in vitro.

The developmental expression of nebulin was studied in embryonic chick skeletal muscle cells in vitro by means of immunofluorescence microscopy. Initially nebulin appeared homogeneously or in a punctate form in the cytoplasm, and then it was assembled into I-Z-I-like complexes containing actin and alpha-actinin but not myosin and connectin (titin). Striated patterns of nebulin ('singlets') in myofibrils appeared simultaneously with those of alpha-actinin (Z-bands), myosin (A-bands) and connectin ('doublets'), but earlier than those of actin. After actin striations were formed as myofibrils matured, each nebulin band started to exhibit 'droplets'. The delayed development of nebulin compared to the I-Z-I brush formation and the myofibril maturation seems to indicate that this giant myofibrillar protein is unnecessary for both the initial (formation of I-Z-I-like structures) and the subsequent (regular alignment of myofibrils) phases of myofibrillogenesis.

Animals↗
PubMed1992

The sequential change of serum 2',5' oligoadenylate synthetase in different infectious patterns of duck hepatitis B virus in ducks in experimental transmission.

Duck hepatitis B virus (DHBV) shows clear age-dependent infectious patterns like that of Hepatitis B virus, and many factors have been assumed to have a role in the persistence of the infection. In the present study, the activities of the interferon-induced enzyme 2',5' oligoadenylate synthetase (2,5AS) were observed sequentially in the serum of ducks experimentally infected with DHBV on posthatch days 1, 7 and 14. These were compared with the infectious pattern to investigate whether the endogenous interferon response after infection in ducks of different ages has a major role in its determination. The infectious pattern of DHBV in 1-day-old ducks was persistent without hepatitis and the others were transient with hepatitis. Persistently infected ducks showed significantly lower activities of 2,5AS compared with those with transient hepatitis, which resulted in a rapid elimination of DHBV. Although 1-day-old ducks showed significantly high 2,5AS compared with non-infected ducks, interferon response alone appeared to be insufficient for the elimination of DHBV. The immune response seemed necessary for the complete elimination of DHBV by way of evoking hepatitis and stimulating more interferon response during the usual infectious course. The interferon system alone did not seem to have a critical role in determining the infectious pattern. Other factors, including the immune response to the virus, seemed to have a major role in this problem.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Regional differences in skin blood flow and temperature during total spinal anaesthesia.

Three patients were studied to determine the changes in regional skin temperature and blood flow during extensive sympathetic blockade following total spinal anaesthesia (TSA). Skin temperature was measured at the right upper arm, the right anterior chest at the nipple level, the right hand and the foot, using infrared thermography. Skin blood flow of the right upper arm (C6 area) was measured with a laser Doppler flowmeter. The temperature of the truncal area, arm and leg decreased by 1 degree C following TSA, whereas the temperature of the hand and foot increased by 3 degrees C. The mean blood flow in three patients decreased to 26.1, 61.4, 51.7% of the control values 15 min after TSA. Our results indicate that extensive sympathetic nervous blockade during total spinal anaesthesia induces regional different changes in skin temperature and decrease in truncal skin blood flow.

Anesthesia, Spinal↗
PubMed1992

Prostaglandin E1 and carbon dioxide reactivity during cerebral aneurysm surgery.

The purpose of this study was to evaluate the effect of prostaglandin E1 (PGE1) on CO2 reactivity during cerebral aneurysm surgery in 37 patients under neuroleptoanaesthesia (NLA). The patients were divided into two groups based on the timing of surgery (A: late surgery B: early surgery). In the early surgery group, aneurysm surgery was performed within three days of subarachnoid haemorrhage (SAH) and in the late surgery group surgery was performed more than four days after SAH. Presurgical neurological status was worse in the early surgery group than in the late surgery group (P less than 0.01). Local cerebral blood flow (LCBF) measurements were made using a thermal gradient blood flow meter. Hypotension was induced by PGE1 administration at an initial dose of 0.1 micrograms.kg-1.min-1 and adjusted to maintain the mean arterial pressure (MAP) at about 70 mmHg. The CO2 reactivity was calculated by the % change in LCBF divided by the change in PaCO2 (% delta LCBF/delta PaCO2 (%.mmHg-1)). LCBF, heart rate and mean arterial blood pressure were measured during and after PGE1 infusion. Carbon dioxide reactivity was measured before, during and after PGE1 administration. The LCBF did not change throughout the study but CO2 reactivity was greater in Group A (before hypotension: 2.74 +/- 0.85 %.mmHg-1, during hypotension: 2.54 +/- 0.73 % .mmHg-1, after hypotension: 2.59 +/- 1.17 %.mmHg-1) than in group B (before hypotension: 1.54 +/- 0.57%.mmHg-1, during hypotension: 1.56 +/- 0.59 %.mmHg-1, after hypotension: 1.49 +/- 0.42%.mmHg-1) (P less than 0.01). Outcome which was graded by Glasgow Outcome Scale at discharge, was better in Group A (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of aging on macrophage adherence to extracellular matrix proteins.

Fibronectin, type I, type IV and type V collagens were compared for their abilities to promote mouse peritoneal resident macrophage adherence and the effect of aging on macrophage adhesion to these matrix proteins was examined. Adherence of macrophages to fibronectin was remarkable and more than 5-fold compared to type I, type IV or type V collagens. Adherence of macrophages to fibronectin and type I collagen increased during aging. However, no age-related changes were observed in macrophage adherence to type IV and type V collagens. The percent of inhibition of macrophage adherence to fibronectin by arginine-glycine-aspartic acid-serine (RGDS) peptide (58.1 +/- 2.7%) was significantly (P < 0.01) higher than that in cells from young mice (23.1 +/- 5.7%). These data suggest that macrophage attach preferentially to fibronectin and that the ability of macrophage to attach to fibronectin increases during aging. The age-related increase in macrophage attachment to fibronectin is related to the concentration of cell surface receptors of macrophage which recognize RGDS sequence within fibronectin during aging. Adherence of macrophage to fibronectin implies retention of macrophages in subendothelial space. Age-related increase in macrophage ability to attach to fibronectin may be related to atherogenesis during aging.

Aging↗
PubMed1992

Effects of fentanyl-diazepam-pancuronium anesthesia on heart rate variability: a spectral analysis.

The effects of induction of anesthesia with fentanyl, 62.1 +/- 7.9 micrograms/kg, diazepam, 0.21 +/- 0.08 mg/kg, and pancuronium on beat-to-beat heart rate variations were studied in seven patients undergoing cardiac surgery. Spectral analysis was used to determine the intensity of the variations in each of the two main frequency bands in which variations are known to occur: (1) high-frequency band, mediated by the parasympathetic nervous system, at the frequency band of respiration, and (2) the low-frequency band, mediated by both sympathetic and parasympathetic nervous systems, at 0.04-0.12 Hz. Both the mean low- and high-frequency band areas were significantly decreased after induction of anesthesia. The ratio of high-to-low frequency band areas increased significantly after induction of anesthesia, from 45% to 62% (P less than 0.05). These results suggest that fentanyl-diazepam-pancuronium anesthesia decreases total autonomic nervous system activity and alters the balance between parasympathetic and sympathetic activities. Thus, spectral analysis of heart rate variations during anesthesia may provide a quantitative measure of assessing the activity of the autonomic nervous system.

Adult↗
PubMed1992

Purification and characterization of a novel thermostable lipase from Pseudomonas cepacia.

A thermostable lipase from Pseudomonas cepacia has been purified to homogeneity as judged by SDS-PAGE and isoelectric focusing. The purification included treatment of the culture supernatant with acrinol, hydrophobic interaction chromatography, and gel filtration. The enzyme was a monomeric protein with M(r) of 36,500 and pI of 5.1. The optimal pH at 50 degrees C and optimal temperature at pH 6.5 were 5.5-6.5 and 55-60 degrees C, respectively, when olive oil was used as the substrate. Simple triglycerides of short and middle chain fatty acids (C < or = 12) were the preferred substrates over those of long chain fatty acids. The enzyme cleaved all the ester bonds of triolein, with some preference for the 1,3-ester bonds. The enzyme retained all its activity even after incubation at 75 degrees C (pH 6.5) for 30 min. Further, the activity was not impaired during 21 h storage at pH 6.5 in 40% water-miscible solvents including methanol, ethanol, acetone, acetonitrile, dimethylformamide, dimethylsulfoxide, and dioxane. The addition of dimethylsulfoxide or acetone to the assay mixture in the range of 0-35% stimulated the enzyme, whereas benzene or n-hexane had an inhibitory effect. These properties together with the N-terminal amino acid sequence confirmed that the enzyme differs from the known Pseudomonas sp. lipases.

Amino Acid Sequence↗
PubMed1992

Hepatic venous hemoglobin oxygen saturation predicts liver dysfunction after hepatectomy.

A fiberoptic flow-directed catheter inserted into the hepatic vein continuously measures hepatic venous oxygen hemoglobin saturation (ShvO2). This study determined whether intraoperatively measured ShvO2 could predict postoperative serum activities of aminotransferases and patient outcome in 83 patients undergoing hepatectomy. The duration of intraoperative ShvO2 less than or equal to 10, 20, 30, 40, and 50% was calculated in each case. Significant increases in postoperative serum aminotransferases were associated with more than 1, 11, 31, 51, and 181 min of duration of ShvO2 less than or equal to 10, 20, 30, 40, and 50%, respectively. The incidence of postoperative liver failure significantly increased when the duration of ShvO2 less than or equal to 20, 30, and 40% exceeded 11, 31, and 51 min, respectively. The mortality from liver failure was significantly higher when the duration of ShvO2 less than or equal to 30 and 40% exceeded 31 and 51 min, respectively. Therefore, intraoperative monitoring of ShvO2 may predict not only the increase in postoperative serum aminotransferases but also patient outcome in terms of postoperative liver failure after hepatectomy.

Adult↗