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Biomedical subjects

S Sakurai

Publications and source records attributed to S Sakurai.

At least 109 records · Page 6Linked to original sources

Inhibitory effect of lead on the repair of wounded monolayers of cultured vascular endothelial cells.

We investigated the effect of lead nitrate (0.5-5.0 microM) on the repair of wounded monolayer of cultured bovine aortic endothelial cells. It was morphologically found that lead decreases the appearance of the cells in the wounded area in a concentration-dependent manner without degenerative changes after a 48-h incubation. Although mercury weakly inhibited the repair with nonspecific cell damage, the other cations including bismuth, cobalt, manganese and nickel failed to affect the repair. The inhibition of endothelial repair caused by lead was observed even when stimulated by exogenous either basic or fibroblast growth factor. These results indicated that inhibition of the repair process of damaged endothelial cell layer is a component of lead-induced vascular lesions such as atherosclerosis.

Animals↗

Transcatheter arterial embolization-induced bilious pleuritis in a patient with hepatocellular carcinoma.

A 52-year-old man with hepatocellular carcinoma (HCC) was admitted with cough and fever. He had undergone four series of treatments, including transcatheter embolization and chemoembolization with lipiodol and anticancer drugs, over the previous 2 years. Computed tomography demonstrated dilated hepatic ducts, localized necrosis in the right hepatic lobe, and subphrenic abscess. He died of respiratory failure, because of increased effusion of the right pleura, about 3 weeks after admission. Autopsy revealed adhesions in the lower lobes of the right lung, diaphragm, and liver, with granulomas with bile pigment. A fistula was observed from the necrotic regions of the right hepatic lobe to the pleura through the diaphragm. A tumor thrombus in the portal trunk was histologically confirmed as well and moderately differentiated HCC with trabecular arrangement. Direct invasion of HCC with necrotic tissue to the pleura through the diaphragm appeared to have caused the respiratory failure. Although bilious pleuritis is a rare complication of transcatheter arterial embolization (TAE), it should be considered as an adverse effect of TAE in patients with a dilated hepatic duct.

Antineoplastic Agents↗

Changes in natural killer cell subpopulations in lead workers.

To investigate the effects of lead on human immune system, we analyzed T cell subpopulations (CD4+, CD8+ and CD3+ cells), natural killer (NK) cell subpopulations (CD16+ and CD57+ cells) and B (CD19+) cells in peripheral blood in 29 male lead workers. All were engaged in manufacturing lead stearate in a chemical factory. They were aged 23-74 (mean 49) years. Their blood lead concentrations (PbB) were between 7 and 35 (mean 18) micrograms/dl. They were divided into two groups according to their PbB: a high-PbB group (> or = 20 micrograms/dl), and a low-PbB group (< 20 micrograms/dl). The control group consisted of 19 "healthy" male workers without a history of occupational exposure to lead or to other hazardous substances, aged 48-67 (mean 58) years. The number and percentage of CD16+ cells in the high-PbB group were significantly lower than those in the controls and in the low-PbB group. There was significant negative correlation between the number of CD16+ cells and PbB in the lead workers. The percentage of CD8+ cells in the high-PbB group was larger than that in the controls and in the low-PbB group. It is suggested that the CD16+ NK cell should be a major site of the effects of lead on lymphocyte subpopulations.

Adult↗

Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells.

Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the increase in intracellular Ca2+ ([Ca2+]i) induced by angiotensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+]i level or the maximal response of [Ca2+]i increase induced by AII. Furthermore, IL-2-induced enhancement was not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimulation of DNA synthesis induced by AII, although IL-2 alone did not stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases, significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-2-induced enhancement of DNA synthesis induced by AII. These findings suggest that autocrine HB-EGF is partially involved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play important roles in the pathogenesis of atherosclerosis and vascular disease by modulating the responsiveness to AII in VSMC.

Angiotensin II↗

Development changes in juvenile hormone and juvenile hormone acid titers in the hemolymph and in-vitro juvenile hormone synthesis by corpora allata of the silkworm, Bombyx mori.

A simple method was developed to quantify hemolymph juvenile hormone (JH) and JH acid in hemolymph extracts from Bombyx mori with an established radioimmunoassay (RIA) for JH I. When various organic solvent extracts of hemolymph were assayed by RIA, levels of non-specific binding of the labeled ligand in the assay were determined to be greater than 50% of the maximum amount of the label bound by the antiserum. When hemolymph was diluted with methanol:water:8.4N ammonium hydroxide (10:9:1) and extracted with isooctane, non-specific binding was only 50% higher than control levels obtained with the assay buffer alone. The organic phase contained only JH and aqueous phase, JH acid. Consequently, this extraction method was used to prepare samples for RIA and enabled the separate measurement of JH and JH acid in hemolymph. With this method, changes in the hemolymph titers of JH and JH acid were determined from the third instar through early pupal stage of Bombyx mori. Changes in the in vitro secretory activity of corpora allata and brain-corpora cardiaca-corpora allata complexes from fifth instar larvae were also determined by using JH I RIA of the incubation medium.

Journal Article↗

Structure and expression of bombyxin E1 gene: a novel family gene that encodes bombyxin-IV, an insect insulin-related neurosecretory peptide.

A bombyxin gene encoding precursor molecule for bombyxin-IV, one of the insulin-related neurosecretory peptide of the silkmoth Bombyx mori, has been cloned and characterized. The nucleotide sequence of this gene and its deduced amino acid sequence deviate moderately from those characterized previously for the family A, B, C and D bombyxin genes. The gene encoding the bombyxin-IV precursor was therefore defined into a novel family E and designated as gene E1. The bombyxin E1 transcript in Bombyx brain was shown to locate in four pairs of medial neurosecretory cells, which also produce other bombyxin family mRNAs, and the amount of the E1 transcript did not change markedly during the fifth larval instar. Genomic Southern hybridization indicated that the Bombyx haploid genome contained a single copy of the bombyxin family E gene.

Amino Acid Sequence↗

Digital ischemia and gangrene due to red blood cell aggregation induced by acquired dysfibrinogenemia.

Digital gangrene was observed in a patient who had angiographic findings of digital arterial occlusion. The patient's blood showed a marked red blood cell aggregation with rouleaux formation in long chains, which could not be dispersed at shear rates up to 200 sec-1. Studies of the patient's blood revealed the presence of an abnormal fibrinogen capable of aggregating normal red blood cells. This fibrinogen was found by Raman spectroscopy to have an increased alpha-helical content, whereas the beta-sheet content was decreased. Defibrinogenation therapy with ancrod resulted in a dramatic symptomatic relief. The disappearance of the abnormal fibrinogen 6 months later and an absence of a family history indicate that this dysfibrinogenemia was acquired.

Arterial Occlusive Diseases↗

Aminoglycosides prevent and dissociate the aggregation of platelets in patients with EDTA-dependent pseudothrombocytopenia.

Although EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is of practical importance because failure to recognize this clinical entity may result in misdiagnosis and subsequent mismanagement of the patients, the pathophysiological nature of EDTA-PTCP remains unknown. To develop an effective way to evaluate the platelet counts in patients with EDTA-PTCP, we introduced aminoglycosides-supplemented anticoagulating agents. When kanamycin was pre-supplemented with EDTA for anticoagulating blood samples from EDTA-PTCP patients there was no significant change in the platelet counts and the morphology of blood cells after 150 min of incubation at room temperature. Furthermore, when kanamycin was added to EDTA-anticoagulated blood samples from EDTA-PTCP patients within 30 min after blood withdrawal, rapid dissociation of platelets without apparent morphological changes of blood cells was observed, and complete blood cell counts as well as the histogram patterns were almost the same as those examined immediately after blood sampling. The dissociation of aggregated platelets was also detected when other antibiotics were used, although it was associated with some extent of morphological changes of blood cells. These findings indicate that the supplementation of aminoglycosides either before or after blood sampling is a useful method for the diagnosis EDTA-PTCP and for the evaluation of platelet counts in patients with EDTA-PTCP.

Adolescent↗

Differential stimulation requirements for IL-12 production among clones of macrophage hybridomas.

We have previously established cloned macrophage hybridomas by somatic cell fusion of the macrophage tumor P388D1 of DBA/2 (H-2d) origin with splenic adherent cells of CKB mice (H-2k). Several cloned lines displayed the serologic and functional characteristics of macrophages. In this study, we evaluated the ability of these hybridomas to produce IL-12 after combined stimulation with IFN-gamma and lipopolysaccharide (LPS). The patterns of IL-12 production by these cloned macrophages fell into three groups. The first group produced IL-12 on stimulation with LPS in combination with IFN-gamma pretreatment, the second group produced IL-12 on stimulation with LPS regardless of the pretreatment with IFN-gamma, and the third group did not produce IL-12 at all on stimulation with IFN-gamma and LPS. None of the macrophage clones tested produced IL-12 constitutively. The results correlated well with IL-12 p40 mRNA expression in those macrophages as detected by RT-PCR. These results suggest the differential stimulation requirements for IL-12 production among macrophages at a clonal level.

Animals↗

Neonatal lupus erythematosus: HLA-DR and -DQ distributions are different among the groups of anti-Ro/SSA-positive mothers with different neonatal outcomes.

Neonatal lupus erythematosus (NLE) is an antibody-mediated disorder of infants characterized by two major clinical manifestations; cutaneous lupus lesions and congenital heart block (CHB). The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. There is a tendency for the same disease expression to occur within a sibship. To reveal a possible association of class II MHC genes with maternal anti-Ro/SSA autoimmune responses and neonatal outcomes in NLE with a relatively homogeneous ethnic background, haplotype, and allele distributions were analyzed based on the PCR-RFLP results in 26 Japanese anti-Ro/SSA-positive mothers from three groups defined by neonatal outcomes. The results were as follows: (i) maternal HLA-DR5 haplotype DRB1*1101-DQA1*0501-DQB1*0301 and individual class II alleles making up this haplotype were significantly associated with neonatal cutaneous lupus but not CHB. Conversely, maternal HLA-DQB1*0602 carried on HLA-DR2 haplotypes was associated with CHB but not cutaneous NLE; (ii) HLA-DQA1 alleles with glutamine at position 34 of the first domain, which have reportedly been associated with the autoimmune responses to Ro/SSA antigens in other ethnic groups, were increased in the mothers of infants with cutaneous involvement; and (iii) there was no particular class II HLA profile that distinguished the disease manifestations in infants. These findings suggest that specific maternal MHC class II genes might correlate with specific neonatal outcomes in NLE.

Adult↗

Effects of job strain on helper-inducer (CD4+CD29+) and suppressor-inducer (CD4+CD45RA+) T cells in Japanese blue-collar workers.

BACKGROUND: The effects of job strain on helper-inducer (CD4+CD29+) T cells and suppressor-inducer (CD4+CD45RA+) T cells are not clear. METHODS: The subjects were 65 male blue-collar workers in a chemical plant in Japan. Perceived job stressors were assessed using the Japanese version of Job Content Questionnaire, i.e., job demands, job control, supervisor support and coworker support. Blood samples were taken from these subjects, and number and percentage of total lymphocytes were calculated for total T cells, helper (CD4+) T cells, suppressor/cytotoxic (CD8+) T cells, helper-inducer (CD4+CD29+) T cells and suppressor-inducer (CD4+CD45RA+) T cells using the double-staining fluorescence. RESULTS: Job control significantly and positively correlated with number and percentage of helper-inducer (CD4+CD29+) T cells, after controlling for age, number of cigarettes per day and blood lead concentration (Spearman's partial correlation, p < 0.05), while job demands, supervisor support or coworker support did not (p > 0.05). The job strain index, i.e., the ratio of job demands to job control, significantly and negatively correlated with the percentage of helper-inducer (CD4+CD29+) T cells (p < 0.05). None of the job stress scales significantly correlated with number or percentage of suppressor-inducer (CD4+CD45RA+) T cells (p > 0.05). CONCLUSIONS: It is suggested that higher job strain or lower job control is associated with a decrease in helper-inducer (CD4+CD29+) T cells in Japanese blue-collar workers.

Adult↗

Soluble form of selectins in blood of patients with acute myocardial infarction and coronary intervention.

Soluble (s) P-selectin, sE-selectin, sL-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) levels were examined by monoclonal antibody-based enzyme immunoassay on serum samples taken from nine patients with acute myocardial infarction (AMI) and eight patients with stable angina pectoris (SAP) before and after the successful percutaneous transluminal coronary angioplasty (PTCA). In patients with acute phase of AMI, the levels (mean +/- SEM) of sP-selectin (110 +/- 18 ng/ml) and sE-selectin (54 +/- 15 ng/ml) before PTCA, were significantly higher than those in the SAP group, the values being 44 +/ 27 and 21 +/- 4 ng/ml (p < 0.05), respectively. After recanalization, the levels of sE-selectin and sL-selectin were significantly decreased (sE-selectin 54 +/- 15 to 42 +/- 11 ng/ml, sL-selectin 1104 +/- 106 to 891 +/- 59 ng/ml, P < 0.05, respectively). These findings suggest that the presence of activated and/or injured endothelial cells, which may be involved in the plaque disruption or intraluminal thrombosis in AMI region and that the inflammatory process may be altered after reperfusion therapy.

Adult↗

Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene D4 of [4-[1-(benzenesulfonamido)alkyl]phenyl]alkanoic acid derivatives.

In order to find new antiasthmatic agents with dual antagonistic activity against thromboxane A2 (TXA2) and leukotriene D4 (LTD4) receptors, synthesis and pharmacological evaluation of various [4-[1-(benzenesulfonamido)-alkyl]phenyl]alkanoic acid derivatives were undertaken. TXA2 and LTD4 antagonistic activities in vitro were evaluated by measuring the inhibitory effects on L-46619-induced contraction of guinea-pig trachea and LTD4-induced contraction of guinea-pig ileum and trachea. Several compounds showed satisfactory dual antagonistic activities, and their effect (after oral administration) on LTD4-induced bronchoconstriction in guinea-pig in vivo was examined. The results demonstrated that both 4-[4-[1-(4-chlorobenzenesulfonamido)hexyl]phenyl]butyric acid (12e) and 4-[4-[1-(4-chlorobenzenesulfonamido)-5-methylhexyl]phenyl]bu tyric acid (12m) possessed good anti-LTD4 activities. Compounds 12e and 12m were then evaluated for other related pharmacological effects involving the arachidonic acid cascade. These compounds appear to be hybrid eicosanoids antagonists having antagonistic activity against contraction of guinea-pig trachea induced by prostaglandin D2 (PGD2) and PGF2 sigma, as well as TXA2 and LTD4 antagonistic activities.

Animals↗

[Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene D4 of benzenesulfonamide derivatives].

In order to find dual antagonists against both thromboxane A2 (TXA2) and leukotriene D4 (LTD4) receptors for a new antiasthmatic agent, various benzenesulfonamide derivatives were synthesized and evaluated for those pharmacological effects. TXA2 and LTD4 antagonistic activities in vitro were evaluated by the inhibitory effects on LTD4-induced and U-46619-induced contraction of guinea-pig trachea. Furthermore, TXA2 and LTD4 antagonistic activities in vivo were evaluated by the inhibitory effects on LTD4-induced and U-46619-induced bronchoconstriction of guinea-pig after oral administration of test compounds. It was found that 4-[5-[1-(4-chlorobenzenesulfonamido)-5-methylhexyl]-2-thi eny l]butyric acid and 4-[5-[1-(4-fluorobenzenesulfonamido)-5-methyl-hexyl]-2-thienyl]but yric acid possess good anti-LTD4 and anti-TXA2 activities by oral administration.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Phylogenetic position and geographic differentiation of the Japanese dormouse, Glirulus japonicus, revealed by variations among rDNA, mtDNA and the Sry gene.

The Japanese dormouse, Glirulus Japonicus, is the only extant lineage that represents this genus and it has been classified as a single species distributed on the three main islands of Japan, namely Honshu, Shikoku and Kyushu. However, individuals collected from Fukui, Wakayama and Kochi Prefectures (southwestern part of Japan) yielded distinctly different profiles of restriction fragments of the nuclear ribosomal DNA (rDNA) spacer from those collected from Yamanashi and Nagano Prefectures (central Japan). The estimated sequence divergence between the two groups was 2.8% on average, which corresponds to a putative divergence some two million years ago. Representing mitochondrial DNA (mtDNA) sequences, 402 bases of cytochrome b gene were determined by direct sequencing and the estimated extent of the sequence divergence between the two groups was 6.5-7%. Differences between the two geographic groups were also substantial in the sequences of about 300 base-fragments from the Y-linked, sex-determining locus, Sry. To assess the phylogenetic relationships between the Japanese dormouse and members of the family Myoxidae, we compared sequences of mitochondrial 12S rRNA gene of Japanese dormice with those of the forest dormouse (Dryomys nitedula) and the common dormouse (Muscardinus avellanarins), two continental genera thought to be closely related to the genus Glirulus. The results showed that the sequences from Japanese dormice were distinct from any sequences of the two continental species and the extent of the differences were somewhat similar to that between the rat (Rattus norvegicus) and the hamster (mesocricetus auratus).

Animals↗

Bombyxin F1 gene: structure and expression of a new bombyxin family gene that forms a pair with bombyxin B10 gene.

Bombyxin F1 gene, a new bombyxin family gene, has been identified. The F1 gene forms a pair with bombyxin B10 gene with an opposite transcriptional orientation and the gene pair F1/B10 is located between bombyxin gene pairs B9/C1 and A7/B7 in a bombyxin gene cluster. The nucleotide sequence of the F1 gene and its deduced amino acid sequence deviate moderately from those characterized previously for the family-A, family-B, family-C, family-D, and family-E bombyxin genes; the bombyxin F1 gene and preprobombyxin F1 share no more than 62% and 53% sequence identities with other bombyxin members, respectively. Harr-plot analysis indicated that the spacer of the F1/B10 gene pair has low sequence similarity with that of other bombyxin gene pairs characterized. The bombyxin F1 mRNA in Bombyx mori brain was shown to locate in four pairs of medial neurosecretory cells, which also produce other bombyxin family mRNAs. Genomic Southern hybridization indicated that the Bombyx haploid genome contains a single copy of the family-F bombyxin gene.

Amino Acid Sequence↗

[Relations of "self-oriented perfectionism" to depression and hopelessness].

The purpose of this study was to construct a new multidimensional self-oriented perfectionism scale (MSPS) and to examine the relationship of self-oriented perfectionism to depression and hopelessness in college students. In Study 1, 26 original items of a new MSPS were administered to 132 students and factor analysis revealed 4 solutions: desire for perfectionism (DP), personal standard (PS), concern over mistakes (CM), and doubting of actions (D). Twenty items of the final MSPS had high reliability and validity as an instrument of measuring self-oriented perfectionism (Hewitt & Flett, 1991). In Study 2, 178 students completed a questionnaire consisting of MSPS, stressor scale, depression scale, and hopelessness scale. PS was negatively related to hopelessness, and CM and D were positively related to both depression and hopelessness. Students with high CM scores had higher depression than those with low CM scores, unrelated to the degree of stress.

Adult↗