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Biomedical subjects

S Komatsu

Publications and source records attributed to S Komatsu.

At least 55 records · Page 3Linked to original sources
PubMed1999

A role of protein kinase C in the regulation of cytosolic phospholipase A(2) in bradykinin-induced PGI(2) synthesis by human vascular endothelial cells.

The purpose of this study was to elucidate the mechanism by which bradykinin (BK) enhances prostacyclin (PGI(2)) production in human umbilical vein endothelial cells (HUVEC). BK-induced enhancement of PGI(2) synthesis was observed in a dose- and time-dependent manner, and it also increased [Ca(2+)](i) followed by enhancement of cytosolic phospholipase A(2) (cPLA(2)) activity. The PKC inhibitors GF109203X and H7 attenuated the BK-induced increase in [Ca(2+)](i) and inhibited the BK-induced PGI(2) synthesis. Phorbol 12-myristate 13-acetate increased cPLA(2) activity and PGI(2) synthesis but failed to alter [Ca(2+)](i). BK increased cPLA(2) mRNA eightfold by 15 min, and this increase was inhibited by pretreatment with the PKC inhibitors. In response to cycloheximide pretreatment, cPLA(2) mRNA was superinduced. These results suggest that BK stimulates PGI(2) synthesis in HUVEC by activation of cPLA(2) by dual mechanisms: an elevation of [Ca(2+)](i) and a PKC-dependent pathway. Moreover, changes in calcium kinetics and expression of cPLA(2) mRNA may underlie the BK-induced PGI(2) enhancement in these cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Rotational Digital Angiography for the Evaluation of Iliac Artery Disease.

Ten cases with iliac artery disease were evaluated using rotational angiography with revolution of the arm of the X-ray tube support unit. The tip of the catheter was advanced to the infrarenal aorta, and contrast medium was injected at a rate of 6-10 ml/second. Digital angiographic images from multiple projection angles were acquired at 15 frames/second with a rotation speed at about 10 degrees/second and a range of greater than 90 degrees. This method made it possible to detect ulcerations of the artery, which could not be visualized using conventional single-plane angiography. The three-dimensional structure of a dissection could also be visualized. In seven cases of occlusive iliac artery disease, comparison with rotational angiography revealed that anteroposterior views of single-plane angiography underestimated the extent of the disease in four cases and overestimated the extent of the disease in one case. In two cases, no additional clinical information was obtained. In conclusion, rotational angiography provides accurate three-dimensional information concerning the lumen of the iliac arteries.

Journal Article↗
PubMed1999

Effect of probucol on intracellular pH and proliferation of human vascular endothelial cells.

We investigated the effect of probucol on the intracellular pH ([pH]i) and proliferation of human umbilical vein endothelial cells (HUVEC), as well as their production of prostacyclin (PGI2). The addition of probucol produced a biphasic shift in [pH]i, with a brief initial acidification followed by a rapid alkaline shift. After pretreatment with EGTA, the initial decrease in [pH]i was abolished, and the subsequent increase was inhibited. After pretreatment with amiloride, only the increase of [pH]i was abolished. These results suggest that the probucol-induced increase of [pH]i was mainly dependent on Na+/H+ exchange and partly on extracellular Ca2+. In contrast, the addition of LDL produced a decrease of [pH]i. Under Ca2+-free condition, [pH]i was further decreased by LDL. In cells pretreated with amiloride, however, [pH]i was not further decreased by LDL. It was found that probucol promoted cell proliferation, and LDL inhibited cell proliferation. Addition of probucol also enhanced prostacyclin generation by HUVEC. This enhancement of PGI2 generation resulted from increased release of Ca2+ from the storage sites, due not only to increased production of inositol 1,4,5-triphosphate (IP3) but also to the increase of [pH]i. These findings may help to explain the antiatherosclerotic action of probucol.

Amiloride↗
PubMed1999

The mechanism of thrombin-induced prostacyclin synthesis in human endothelial cells with reference to the gene transcription of prostacyclin-related enzymes and Ca2+ kinetics.

This study was designed to evaluate the effect of thrombin on prostacyclin (PGI2) production in cultured human vascular endothelial cells in association with intracellular Ca2+ and with the gene expression of prostaglandin H2 synthase (PGHS) and phospholipase A2 (PLA2) using competitive polymerase chain reaction. Thrombin enhanced the PGI2 synthesis dependent with time. Additionally, thrombin increased the intracellular Ca2+, which stimulates PLA2, resulting in arachidonic acid cleavage from membrane phospholipids and its subsequent conversion into PGI2 through the PGHS pathway. The elevation of intracellular Ca2+ was a result of Ca2+ influx and Ca2+ release from its intracellular storage sites. In this study, PGHS-1 mRNA was constitutively expressed, whereas PGHS-2 mRNA was not. With the stimulation of thrombin, cytosolic PLA2 (cPLA2) mRNA increased 9-fold at 15 min, PGHS-1 mRNA increased 3.4-fold at 180 min, and PGHS-2 mRNA increased 38-fold at 60 min. These results suggest that the elevation of intracellular Ca2+ and the expression of cPLA2, PGHS-1, and PGHS-2 mRNA cause PGI2 generation.

Calcium↗
PubMed1999

Studies on the kinetics, metabolism and re-utilisation after intra-articular administration of hyaluronan to rabbits.

The pharmacokinetics of hyaluronan (HA) (CAS 9004-61-9) was measured after intra-articular (i.a.) injection of 1 mg/kg of 14C-glucose-labelled HA (14C-HA) (i.e. 2,000 kDa) into the knee joint cavity of rabbits. The movement of HA from the cavity into the systemic circulation was assessed by measuring its concentration in blood and its residue in the cavity. I.a. HA moved into, and disappeared from, the bloodstream at a first-order rate. Synovial fluid, synovial membrane and articular cartilage specimens were taken 24 and 72 h post-injection, and the molecular weight (MW) of HA fractions were measured by using gel filtration chromatography (GFC) using radioactive fractions of known molecular sizes (i.e. 2,000 kDa, 300 kDa and 50 kDa). The radioactivity distribution of synovial fluid had a peak at a 2,000 kDa-equivalent fraction at both 24 and 72 h post-injection, while synovial membrane had a peak at a 300 kDa-equivalent fraction 24 h post-injection and at a 50 kDa-equivalent fraction 72 h post-injection. The radioactivity distribution pattern of articular cartilage showed peaks corresponding to 2,000-300 kDa 24 h post-injection and to 50 kDa 72 h post-injection. The in vivo re-utilisation of i.a. HA was investigated by assessing radioactivity in the acid-soluble, lipid and protein fractions of plasma, blood cells and liver 72 h post-injection. Results show that HA was broken down into C1 units (carbon cycle) before being re-used as an in vivo constituent in the body.

Animals↗
PubMed1999

Interleukin-1alpha stimulated prostacyclin release by increasing gene transcription of prostaglandin H synthase and phospholipase A2 in human vascular endothelial cells.

This study was conducted to evaluate the effects of interleukin-1alpha (IL-1alpha) on prostacyclin (PGI2) production in cultured human vascular endothelial cells in association with intracellular Ca2+, inositol 1,4,5-trisphosphate (IP3), and with prostaglandin H synthase (PGHS) and phospholipase A2 (PLA2) gene expression by using the competitive polymerase chain reaction (PCR) method. IL-1alpha did not increase PGI2 production for 15 min, but induced an increase of about three-fold relative to that in controls at 60 and 180 min. IL- 1alpha had no effect on intracellular Ca2+ levels throughout the experimental period. In this study, consistent with previous reports, PGHS-1 messenger RNA (mRNA) was constitutively expressed, whereas PLA2 mRNA was not. After stimulation with IL-1alpha, PLA2 mRNA level showed an eightfold increase within 15 min, and PGHS-2 mRNA level increased by 76-fold within 180 min. PGHS-1 mRNA level was increased 1.6-fold at 180 min. These results suggest the existence of regulatory mechanisms of IL-1alpha-induced PGI2 production, which involve PGHS and PLA2 gene transcription.

Base Sequence↗
PubMed1999

Phosphorylation of proteins in the stem section of etiolated rice seedling irradiated with red light.

The molecular mechanism of light signal perception was analyzed using stem sections of etiolated rice (Oryza sativa L.) seedlings irradiated with red light from a fluorescent lamp. The membrane and cytosol fractions were labeled by 40 nM [gamma-32P]ATP for 10 s at 0 degrees C and proteins were separated by two-dimensional polyacrylamide gel electrophoresis. Phosphorylation of three proteins with molecular weights of 16, 17 and 18 kDa in the rice increased with the intensity of red light irradiation (50 micromol/m2/s) for 16 min. Most of the phosphorylation activity was present in the cytosol fraction. The three proteins cross-reacted with the anti-nucleoside diphosphate (NDP) kinase antibody. Phosphorylation of these proteins was correlated with changes in the activity of NDP kinase. These proteins phosphorylated histone III-S, a substrate for measuring the protein kinase activity. By phospho-amino acid analysis, phosphoserine was found present in the phosphorylated proteins. These rapidly phosphorylated proteins would thus appear to have the features of NDP kinase.

Amino Acid Sequence↗
PubMed1999

N-terminal amino acid sequences of prolamins encoded by the alleles at the Pro1 and Pro2 loci in foxtail millet, Setaria italica (L.) P. Beauv.

N-terminal amino acid sequences of six prolamins encoded by seven alleles at two loci, Pro1 and Pro2, of foxtail millet (Setaria italica (L.) P. Beauv.) were analyzed and compared with other prolamins of subfamily Panicoideae. Based on the N-terminal amino acid sequences, band 3 (the prolamin purified from band 3) which is controlled by an allele at the Pro1 locus and bands 1, 2, 4, 5 and 6 which are controlled by alleles at the Pro2 locus could be classified into three groups. Band 3 was found to be homologous to the prolamin of pearl millet (Pennisetum americanum) and is designated as the "pennisetin-like prolamin". Bands 2 and 4, and bands 1, 5 and 6 were subdivided into "x-type prolamin" and "y-type prolamin". Both of the x-type and y-type prolamins showed homology with prolamin of Echinochloa crus-galli and alpha-zein-like prolamins of maize, sorghum and Job's tears. Therefore, these prolamins were designated as "alpha-zein-like prolamin". These results suggest that alleles at the Pro1 locus and those at the Pro2 locus have not arisen from an identical ancestral gene, and that the Pro2 locus comprise two tightly linked genes, which encode similar prolamins. Hypotheses on the diversification of alleles at the Pro2 locus are discussed based on the N-terminal amino acid sequences of the respective bands, combinations of bands controlled by the alleles, and frequencies of the alleles.

Alleles↗
PubMed1999

Serum retinol level and risk of subsequent cervical cancer in cases with cervical dysplasia.

We followed up on 134 women who had been diagnosed with cervical dysplasia to examine the relationship of dietary and serum vitamin A to subsequent cervical cancer. The subjects were women attending the Papanicolaou test screening for residents in Miyagi, Japan and histologically diagnosed as having cervical dysplasia between October 1987 and September 1988. Personal interviews were carried out, and blood samples were taken on the date of diagnosis of cervical dysplasia. The subjects were followed-up with cervical smear and colposcopy at about 3-month intervals from the date of interview until the end of February 1995. During the follow-up, 8 women (5.9%) developed cancer in situ or invasive cervical cancer and 106 (79.1%) reverted to normal. The rate of progression of the cancer in situ or invasive cervical cancer was 4.5 times higher in women with lower serum retinol levels than those with higher serum retinol levels (p = 0.08). The results suggest an association of low serum retinol level with development of cervical cancer.

Adolescent↗
PubMed1998

Estimation of shunt flow in coronary-pulmonary fistula by lung perfusion scintigraphy with technetium-99m macroaggregated albumin.

The shunt flow from the coronary artery to pulmonary arteries was evaluated in 6 patients with coronary-pulmonary fistula by lung perfusion scintigraphy with technetium-99m macroaggregated albumin. In 2 patients, whose degree of visualization of pulmonary arteries by coronary angiography was relatively high, lung perfusion scintigrams demonstrated the defects at the distal of coronary-pulmonary fistulas.

Aged↗
PubMed1998

Right hepatic lobectomy and subsegmental resection of the left caudate lobe for gallbladder carcinoma involving the hepatic hilus: preservation of the ventral portion of the left caudate lobe.

A case of gallbladder carcinoma in a 75-year-old woman with familial hyperbilirubinemia and preoperative hepatic dysfunction is presented. Tube cholangiography through a percutaneous transhepatic biliary drainage (PTBD) catheter demonstrated a stricture and the hepatic confluence without filling of the gallbladder and showed two bile duct branches arising from the left caudate lobe. Cholangiography also disclosed that the left dorsal branch, which joined the right hepatic bile duct, was involved with tumor, while the left ventral branch, which joined the left hepatic duct, was not. Extended right hepatic lobectomy with resection of the dorsal portion of the left caudate lobe, preserving the ventral portion of the left caudate lobe, was performed. Postoperative cholangiography showed that the ventral branch of the left caudate lobe bile duct was preserved. Precise preoperative anatomic diagnosis of the biliary system in patients with hepatobiliary cancer allows successful subsegmental resection of the caudate lobe.

Aged↗
PubMed1998

Memory for subject performed tasks in patients with Korsakoff syndrome.

We examined the ability of alcoholic Korsakoff patients to remember verbal and action-related information. Eight Korsakoff patients and eight alcoholic control subjects learned action phrases in either subject-performed tasks (SPTs) or verbal tasks (VTs). Free recall and recognition tests were then administered. Despite the severe anterograde amnesia observed in Korsakoff patients for VTs, their memory performance for SPTs was similarly facilitated over VTs as was the case with alcoholic controls. Domains preserved in this amnesic syndrome may account for the benefit seen when using SPTs in Korsakoff patients. The therapeutic utilization of action events for memory rehabilitation is discussed.

Adult↗
PubMed1998

Maternal adrenocortical hormones maintain the early development of pancreatic B cells in the fetal rat.

To investigate the effect of maternal adrenocortical hormones on the development of fetal pancreatic islet cells, pregnant rats were adrenalectomised on d 6 of gestation. On d 12-16 the growth patterns of fetal insulin-producing B cells, glucagon-producing A cells, and somatostatin-producing D cells were observed histometrically. Maternal adrenalectomy resulted in growth retardation of fetal B cells on d 12-15. Maternal corticosterone therapy prevented this retardation. Maternal adrenalectomy, however, did not affect the developmental patterns of A and D cells. By Western blotting and immunohistochemistry, glucocorticoid receptors were demonstrated to be present in the islet cells from d 12 to d 15. These results suggest that maternal adrenocortical hormones, glucocorticoids in particular, maintain the early development of fetal pancreatic B cells through their specific intracellular glucocorticoid receptor.

Adrenal Cortex Hormones↗
PubMed1998

Two statoacoustic ganglion (SAG) cells holding a common perikaryal myelin sheath in between in the chick.

Ganglion cells of the eighth cranial nerve in vertebrates have perikaryal myelin sheaths. The present electron microscopic study showed a case of two statoacoustic ganglion (SAG) cells holding a common perikaryal myelin sheath in between in the chick. Observations of numbers and terminals of myelin lamellae suggested that the sheath would be composed of an abortive lamella sandwiched between respective perikaryal myelin sheaths of the two SAG cells. The outer surface of the two perikaryal sheaths was covered by a continuous basal lamina. The process of common myelin sheath formation is discussed.

Animals↗
PubMed1998

Human pancreatic RNase1-human epidermal growth factor fusion: an entirely human 'immunotoxin analog' with cytotoxic properties against squamous cell carcinomas.

The gene encoding human pancreatic ribonuclease 1 (hpRNasel) was fused with a gene encoding human epidermal growth factor (hEGF). The hybrid human protein was isolated from Escherichia coli inclusion bodies, refolded and purified to homogeneity. The fusion protein competed with 125I-hEGF for binding to hEGF receptors (EGFR) and had ribonucleolytic activities approaching those of hpRNase1. Several conformations having different enzymatic activities could be detected after reversed-phase high-performance liquid chromatographic analysis, the less hydrophobic molecules being the most active. The hybrid protein was specifically cytotoxic to A431, an EGFR overexpressing squamous carcinoma cell line, with an IC50 of approximately 10(-7) M. In contrast, recombinant hpRNase1 had an IC50 higher than 10(-4) M. A mixture of free hEGF and free hpRNasel was not more cytotoxic than hpRNasel alone and no cytotoxicity was detected in EGFR-deficient control cells. Taken together, these data suggest that this construct might be useful for targeted therapy of esophageal, lung and other squamous cell carcinomas and also breast cancers overexpressing EGFR, which correlate with a poor prognosis and cannot be cured by surgery alone. Engineering hybrid molecules with endogenous human proteins for targeted therapy may alleviate the dose-limiting immunogenicity and toxicity of conventional immunotoxins.

Binding, Competitive↗
PubMed1998

Inhibition of 15-hydroxyprostaglandin dehydrogenase activity in rabbit gastric antral mucosa by panaxynol isolated from oriental medicines.

Panaxynol is a polyacetylene compound with anti-inflammatory and anti-platelet-aggregatory effects isolated from commonly used oriental medicines. The effects of panaxynol on the activity of prostaglandin-synthesizing and catabolizing enzymes in the rabbit gastric antral mucosa have been examined. At concentrations ranging from 25 to 200 microM panaxynol had no effect on the synthesis of prostaglandins E2, F2alpha and D2 from exogenous arachidonic acid in the microsomal fraction of the gastric mucosa whereas at 25-200 microM it dose-dependently inhibited the activity of 15-hydroxyprostaglandin dehydrogenase (PGDH), which catalyses the initial step of prostaglandin catabolism, in the cytosolic fraction. The concentration required for 50% inhibition (IC50) was approximately 25 microM. Inhibition of PGDH by panaxynol was non-competitive with regard to NAD+ and prostaglandin E2. These results suggest that panaxynol has the potential to inhibit PGDH activity in gastric mucosa, possibly as a result of pharmacological activity.

Alkynes↗
PubMed1998

ICAM-1 and P-selectin expression in a model of NSAID-induced gastropathy.

A growing body of experimental evidence suggests that neutrophilic polymorphonuclear leukocyte (PMN)-endothelial cell interactions play a critical role in the pathophysiology of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. The objective of this study was to directly determine whether the expression of endothelial cell adhesion molecules is enhanced in a model of NSAID-induced gastropathy. Gastropathy was induced in male Sprague-Dawley rats via oral administration of indomethacin (Indo, 20 mg/kg). Lesion scores, blood-to-lumen clearance of 51Cr-EDTA (mucosal permeability), and histological analysis (epithelial necrosis) were used as indexes of gastric mucosal injury. Gastric mucosal vascular expression of intercellular adhesion molecule 1 (ICAM-1) or P-selectin were determined at 1 and 3 h after Indo administration using the dual radiolabeled monoclonal antibody (MAb) technique. For some experiments, a blocking MAb directed at either ICAM-1 (1A29) or P-selectin (RMP-1) or their isotype-matched controls was injected intravenously 10 min before Indo administration. We found that P-selectin expression was significantly increased at 1 h but not 3 h after Indo administration, whereas ICAM-1 expression was significantly increased at both 1 and 3 h after Indo treatment. The blocking ICAM-1 and P-selectin MAbs both inhibited Indo-induced increases in lesion score, mucosal permeability, and epithelial cell necrosis. However, the Indo-induced gastropathy was not associated with significant PMN infiltration into the gastric mucosal interstitium, nor did Indo reduce gastric mucosal blood flow. We propose that NSAID-induced gastric mucosal injury may be related to the expression of P-selectin and ICAM-1; however, this mucosal injury does not appear to be dependent on the extravasation of inflammatory cells or mucosal ischemia.

Animals↗