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Biomedical subjects

Y Sekiguchi

Publications and source records attributed to Y Sekiguchi.

At least 55 records · Page 3Linked to original sources
PubMed1993

Prostaglandin E2 stimulates cyclic AMP-mediated hyaluronan synthesis in rabbit pericardial mesothelial cells.

We studied the effects of prostaglandin E2 (PGE2) on hyaluronan synthesis in rabbit pericardial mesothelial cells, and the following results were obtained. (1) PGE2 (10-1000 ng/ml) stimulated hyaluronan synthesis and the level of hyaluronan synthase activity in a dose- and time-dependent manner, but PGF2 alpha did not. (2) Cyclic AMP (cAMP) levels in the cells peaked (about a 7-fold increase) at 5-10 min after adding PGE2 (1000 ng/ml). (3) Increased hyaluronan synthesis induced by PGE2 was significantly inhibited after pretreatment with either an adenylate cyclase inhibitor (2',5'-dideoxyadenosine) or a cAMP-dependent protein kinase inhibitor (PKI 5-24), but there was no inhibition with the protein kinase C inhibitor H-7. (4) When the intracellular cAMP level was raised by manipulating the levels of dibutyryl cyclic AMP or forskolin, hyaluronan synthesis and the level of hyaluronan synthase activity were also stimulated. These results suggest that PGE2 produced by cells stimulates hyaluronan synthesis in rabbit pericardial cells and that the stimulation mechanism involves the cAMP-mediated protein kinase signal transduction process.

Adenylyl Cyclase Inhibitors↗
PubMed1991

Elevation of plasma endothelin concentrations during endotoxin shock in dogs.

The effect of endotoxin on the release of endothelin, a novel potent vasoconstrictor peptide, was examined in anesthetized dogs and in cultured endothelial cells. Administration of 2.63 mg lipopolysaccharide, E. coli 0111:B4/kg body weight caused shock in the animals and produced a long-lasting increase in the plasma immunoreactive endothelin-1 level that remained higher than the basal level (1.83 pg/ml as mean level) from 30 to 120 min after the injection, with a peak at 90 min (8.15 pg/ml as mean level). In vitro immunoreactive endothelin-1 in a culture medium, in which calf pulmonary artery endothelial cells were incubated in the presence of 10% fetal bovine serum, increased dose dependently with the concentration of added lipopolysaccharide between 0.01 and 10 micrograms/ml. These data indicate that plasma endothelin increases during endotoxin shock and that stimulation by endotoxin, per se, in the presence of serum participates at least partially in the mechanism for its release.

Adrenocorticotropic Hormone↗
PubMed1991

Photodynamic therapy using pheophorbide a and Nd:YAG laser.

The authors describe a new photodynamic therapy (PDT) method for malignant brain tumors. Pheophorbide a (Ph-a), the photosensitizer, has low toxicity, causes no skin sensitization and is activated with an acoustic Q switched neodymium yttrium-argon-garnet (Nd:YAG) laser which achieves deep tissue penetration. The Ph-a distribution in Fisher 344 (F344) rats bearing rat T9 glioma at 24 hours after intravenous injection was very low in the normal brain tissue, but significantly higher in the T9 glioma giving a tumor to normal brain tissue concentration ratio of 7.5:1. The in vitro survival rate of T9 glioma cells pretreated with Ph-a was 68.8 +/- 5.4% after laser irradiation for 20 minutes, significantly lower than in the control groups. This indicates that Ph-a was activated with the acoustic Q switched Nd:YAG laser causing the photodynamic effect. The survival rate after Ph-a pretreatment and laser irradiation in a waterbath at 44.0 degrees C was further reduced to 15.8 +/- 3.3%. In vivo PDT studies using T9 glioma cells inoculated into the dorsal region of F344 rats showed tumor eradication in four of six rats. The combination of PDT and laser hyperthermia produced tumor eradication in all six rats. The combination of PDT and hyperthermia is a promising method for tumor treatment.

Animals↗
PubMed1989

Molecular cloning and expression of rat interleukin-1 alpha cDNA.

A cDNA sequence coding for rat interleukin-1 alpha (IL-1 alpha) has been isolated from a cDNA library that was prepared with mRNA derived from LPS-stimulated rat peritoneal macrophages by using human IL-1 alpha cDNA as a probe. The rat cDNA encodes a 270 amino acid residue protein which is homologous (65%) to human IL-1 alpha. The rat cDNA sequence under SV40 early promoter directed the synthesis of biologically active IL-1 in monkey COS-1 cells. Rat IL-1 alpha mRNA is not expressed in spleen, lung, liver or brain, and is also not expressed in these organs of LPS-treated rat except spleen. This suggests that IL-1 alpha is not produced constitutively in various tissues and LPS is not sufficient to induce IL-1 alpha in most tissues. Our data indicate that the IL-1 activities which have been reported to be produced in the brain are not of alpha type. We have constructed a plasmid expressing the carboxy terminal 156 amino acids in Escherichia coli. Recombinant rat IL-1 alpha produced in COS cells or E. coli has cytotoxic activity against the human melanoma cell line A375S1 (GIF activity), which has been reported to be sensitive to human IL-1 alpha and IL-1 beta. This suggests that GIF activity is common to IL-1s derived from various sources.

Amino Acid Sequence↗
PubMed1989

Impaired accessory cell function of monocytes in systemic lupus erythematosus.

We studied the ability of monocytes from systemic lupus erythematosus (SLE) patients to act as accessory cells in an in vitro antibody response. Depletion of monocytes from peripheral blood mononuclear cells of normal subjects caused markedly diminished immunoglobulin (Ig) production but that of SLE did not. In order to evaluate the accessory cell activity of monocytes in in vitro immunoglobulin (Ig) production, we designed an accessory cell index of monocytes in the antibody responses. The studies revealed that Ig synthesis of isologous lymphocytes, mixed with monocytes from patients with active lupus nephritis, was significantly lower than those mixed with monocytes from healthy subjects. Moreover, the addition of graded numbers of monocytes of the former to unseparated peripheral blood mononuclear cells did not alter in vitro antibody production. These results indicate that monocytes from active SLE patients have an impared accessory cell function in an in vitro antibody response with no stimulating effect on suppressor cell activity.

Antibody-Producing Cells↗
PubMed1989

Accessory cell activity of monocytes in anti-DNA antibody production in systemic lupus erythematosus.

Depletion of monocytes from peripheral blood mononuclear cells of patients with systemic lupus erythematosus (SLE) resulted in a decreased anti-DNA antibody synthesis in vitro. The addition of monocytes restored the response by lymphocytes and the maximum response in the presence of 2.5-8% of monocytes, whereas greater than 15% of monocytes caused rather decreased antibody responses. In order to further evaluate the role of monocytes on an anti-DNA antibody synthesis, we designated an accessory cell index, based on reconstitution experiments using isologous SLE lymphocytes, and compared it in active or inactive SLE and controls. The studies revealed that active SLE monocytes enhanced spontaneously occurring anti-DNA antibody synthesis by SLE lymphocytes. These results indicate that SLE monocytes actively participate in spontaneously occurring anti-DNA autoantibody synthesis in humans.

Antibodies, Antinuclear↗
PubMed1989

[The effect of celiac plexus block on splanchnic circulation; changes in systemic hemodynamics and tissue blood flow of the liver and kidney in rabbits].

The effects of the celiac plexus block (CPB) on the hepatic and renal tissue blood flow (TBF) were investigated in 45 rabbits. Together with this, the effects of drugs (phenylephrine: PE, norepinephrine: NE, dopamine: DA, 6% hydroxyethyl starch: HES) used to increase mean blood pressure (MBP) up to control level were also investigated. TBF was measured by the hydrogen clearance method. Following CPB, MBP and heart rate decreased significantly. TBF of the liver and kidney both decreased significantly for 14.3% and 25.9% respectively. A correlation was observed between the decreases of MBP and renal TBF. An increase in hepatic TBF beyond the control level was observed in DA group, and in both hepatic and renal TBF in the HES group after adjustment of MBP. In other groups, both hepatic and renal TBF tended to decrease. It was concluded that hepatic and renal TBF decreased because of hemodynamic suppression following CPB. The results also suggest that both TBFs would have increased if systemic hemodynamic change was not so great.

Animals↗
PubMed1989

[Effects of celiac plexus block on splanchnic circulation--II: Changes in the systemic hemodynamics and the blood flow of the liver and kidney in dogs].

Effects of celiac plexus block (CPB) on systemic and splanchnic circulation, especially of liver and kidney, were investigated in twenty nine mongrel dogs. CPB was performed by an anterior approach through a catheter placed in a paraaortic compartment using 7 mg.kg-1 of 2% mepivacaine. Tissue blood flow measurement was performed by a hydrogen clearance method in eleven dogs, and vascular blood flow was measured in eighteen dogs by an electromagnetic flow meter. Swan-Ganz catheter was inserted to measure mean arterial pressure (ABP), heart rate (HR), central venous pressure (CVP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP) and cardiac output (CO). Then stroke volume (SV), systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were calculated. Following CPB, ABP, HR, CVP and C.O. were significantly decreased at 7 to 9%. PAP decreased at 5%. PCWP, SV, SVR and PVR were unchanged. The hepatic arterial blood flow increased significantly, and portal venous blood flow decreased after CPB transiently, and then recovered to control value or to a higher level at 60min after CPB. The tissue blood flow of the liver tended to increase, but the change was not significant. In the kidney, both arterial and tissue blood flows increased significantly after CPB. The results suggest that following CPB, hepatic and renal tissue blood flows increased because of the increments of their arterial blood flows, unless a profound systemic hemodynamic depression occurred.

Animals↗
PubMed1987

[Effects of TJN-101, a lignan compound isolated from Schisandra fruits, on liver fibrosis and on liver regeneration after partial hepatectomy in rats with chronic liver injury induced by CCl4].

TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. 1) Effect of TJN-101 on liver fibrosis was investigated in rats which were injected with CCl4 (1 ml/kg) subcutaneously twice a week for 12 weeks. TJN-101 was given orally at the dose of 10 or 30 mg/kg/day for 6 or 3 weeks beginning on the 6th or 9th week after the start of CCl4-intoxication, respectively. The elevations of serum transaminase activities and the increase of liver 4-hydroxyproline content were observed depending on the period of CCl4-intoxication. These changes were marked on the 9th and 12th weeks after. In the histopathological study, the degenerative fatty change on the 6th week after and the formation of pseudolobule caused by fibrosis proliferation on the 9th or 12th week after were mainly observed. When rats were treated with TJN-101, the abnormalities in biochemical parameters and the fibrosis proliferation caused by CCl4-intoxication were improved. 2) Chronic liver injury was induced by the treatment with CCl4 (1 ml/kg) subcutaneously twice a week for 10 weeks to investigate the effect of TJN-101 on liver regeneration after partial hepatectomy. TJN-101, which was given orally at the dose of 10, 30 or 100 mg/kg/day for 6 days from the 1st day after partial hepatectomy, dose-dependently increased the liver regeneration rate and improved the serum BSP retention rate. These results suggest that TJN-101 suppresses the fibrosis proliferation and accelerates both the liver regeneration and the recovery of liver function after partial hepatectomy in chronic liver injury.

Administration, Oral↗
PubMed1986

[Effects of TJN-101 ((+)-(6s,7s,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy-6,7 -dimethyl-10,11-methylenedioxy-6-dibenzo [a,c] cyclooctenol) on liver regeneration after partial hepatectomy, and on regional hepatic blood flow and fine structure of the liver in normal rats].

Effects of TJN-101, one of the components isolated from Schizandra fruits, on liver regeneration after partial hepatectomy, and on regional hepatic blood flow and fine structure of the liver were investigated in normal rats. TJN-101, which was administered orally at the doses of 10, 30 and 100 mg/kg/day for 4 days after partial hepatectomy, increased the regeneration rate of the liver and improved the serum retention rate of BSP which had been dose-dependently decreased after the operation. Elevation of serum protein to control levels, elevation of serum LCAT activity, decrease in plasma insulin and increase in plasma glucagon were all dose-dependent responses to TJN-101. The mitotic index on the 5th day after the operation was hardly influenced by TJN-101. Regional hepatic blood flow was increased after intraduodenal administration of TJN-101 (30 and 100 mg/kg). Ultrastructural studies of liver tissue using the transmission electron microscope revealed that TJN-101 stimulated an increase in rough and smooth endoplasmic reticulum in the groups receiving 100 and 300 mg/kg/day. These results suggest that TJN-101 accelerates both the proliferation of hepatocytes and the recovery of liver function after partial hepatectomy and increases hepatic blood flow. It is also thought that the liver enlargement caused by repeated administration of TJN-101 is associated with the proliferation of endoplasmic reticulum.

Animals↗
PubMed1985

Monoclonal human anti-DNA antibodies from EB virus-transformed lymphocytes of systemic lupus erythematosus (SLE) patients.

Sixteen monoclonal human anti-DNA antibodies were obtained from Epstein-Barr virus-transformed lymphoblastoid cells of patients with systemic lupus erythematosus (SLE) and were studied in terms of antigenic specificity. All of the antibodies showed polyspecificity to polynucleotides. Among them, some antibodies had a specificity to single-stranded (ss) DNA. Especially, O-8 antibodies showed a preference for polynucleotides with pyrimidine bases. The binding specificity of the antibody was also studied using different sizes of dT oligomers in order to assess the size of the epitope. It was revealed that oligonucleotides with a size of more than 25-30 nucleotides are required for inhibition of the antibody to ss-DNA. Other studies also demonstrated that anti-ss-DNA (O-8) antibody and anti-double-stranded (ds) DNA (NE-28) antibody bound to different combining sites in the same polynucleotides, poly(dT). These results suggest that some anti-ss-DNA antibodies are directed to the conformational structure related to the base sequence and that nucleic acids, therefore, might be responsible for the possible immunogenic stimulus causing the anti-DNA immune response. We also indicate that this type of antibody would be popular among serum anti-DNA antibodies in SLE.

Antibodies, Monoclonal↗
PubMed1984

Establishment of human monoclonal anti-DNA antibody producing cell lines.

We developed a useful method for the establishment of stable cell lines producing human monoclonal anti-DNA antibody by in vitro Epstein-Barr virus infection. The practical limitation for the cloning was overcome by 2 procedures. One was a microculture system using a small number of the culture. Another was enrichment of anti-DNA producing cells at an early stage and prior to the cloning. The combination of these procedures allowed ready derivation of the cell lines secreting monoclonal anti-DNA antibody. Sixteen cell lines were cloned by utilizing colony formation methods in soft agarose. About 14-32 micrograms per ml of IgM with specific antibody activity were obtained in the supernatant of the cells. The antibody reacted with double-stranded and/or single-stranded DNA. These cells have been continuously producing the specific antibody for more than 3 years. We may extend this procedure for obtaining other autoantibodies, such as anti-T cell antibodies.

Animals↗