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Biomedical subjects

H Seki

Publications and source records attributed to H Seki.

At least 145 records · Page 8Linked to original sources
PubMed1995

Endothelin-1 regulates human decidual cells through both A- and B-type receptors.

The aims of this study were to investigate the effects of endothelin-1 (ET-1) on first trimester human decidual cells, identify the ET receptor sub-types through which these effects are mediated and assess the role of cyclic AMP in any effects of ET-1. ET-1 increased prostaglandin production by first trimester decidual cells, which was consistent with similar studies in third trimester decidual cells. The endothelin A-type receptor (ETA) was coupled to the increased prostaglandin production from first trimester cells, as shown by the inhibitory effects of BQ610, an ETA receptor antagonist. The time course of this effect was unusual, with a rapid increase peaking after 6 h of stimulation, followed by a longer effect over 12-24 h, which was paralleled by changes in cyclic AMP production. No evidence was obtained for any involvement of cyclic AMP in mediating the effects of ET-1 on prostaglandin production. ET-1 also increased decidual prolactin production with a maximum effect after 6 h of stimulation. This was mediated through the ETB receptor and may be linked to increased cyclic AMP production, indicating that the ETA and ETB receptors were coupled to different second messenger systems and affected decidual cell function in different ways.

Cyclic AMP↗
PubMed1995

An essential role of prostaglandin E on mouse mast cell induction.

We previously established a system for induction of mucosal-type mast cells from mouse spleen cells by long term culture without exogenous IL-3. FCS was important and was able to be divided into mast cell-inducible and non-mast cell-inducible sera. LPS contaminated in FCS was responsible for the mast cell induction. However, we unexpectedly found that both supernatants recovered from the cultures with mast cell-inducible and non-mast cell-inducible sera contained endogenous IL-3. Furthermore, addition of rIL-3 to the cultures with non-mast cell-inducible sera had no effect or induced only a small number of mast cells. This indicates that IL-3 alone is not enough for mast cell induction and that some inflammatory factor(s) induced by LPS is also essential. Prostaglandin E1 (PGE1) and PGE2 induced mast cells in a dose-dependent manner when added into the cultures. The activity of LPS for mast cell induction was inhibited by indomethacin. However, indomethacin failed to inhibit the mast cell induction by exogenous PGE. Exogenous PGE antagonized the indomethacin-induced inhibition of mast cell induction by LPS. Cholera toxin and dibutyryl cyclic AMP (cAMP) also induced mast cells. The A and B subunits of cholera toxin, PGF2 alpha, PGD2, and dibutyryl cGMP failed to induce mast cells. Furthermore, mast cell induction by PGE was dose-dependently suppressed by inhibitors for cAMP-dependent A kinase. The above results show that for mast cell induction, IL-3 needs the cooperation of PGE or other stimulants that can elevate the production of the second messenger cAMP in mast cell precursors.

Animals↗
PubMed1995

Neural cell adhesion molecule and perineural invasion in gallbladder cancer.

To clarify the role of neural cell adhesion molecule (NCAM) in perineural invasion, NCAM expression was studied by immunohistochemical staining in 26 cases with gallbladder cancer. In gallbladder cancer, the incidence of perineural invasion and that of positive NCAM expression was 42% and 31%, respectively, which are less frequent than those of bile duct cancer in our previous report. Perineural invasion was observed in 88% of the patients with positive expression of NCAM and in 22% of those with negative expression. The former is similar to that of bile duct cancer but the latter is significantly lower. Eighty percent of the cancer cells that invaded the perineural space were positive for NCAM, when the primary tumor was positive for NCAM expression. Therefore, in gallbladder cancer, positive cells in NCAM expression likely invade the perineural spaces. However, the perineural invasion of negative cells in NCAM expression is not likely to occur as compared to bile duct cancer. In conclusion, perineural invasion in gallbladder cancer is not as common as in bile duct cancer, but the role of NCAM in perineural invasion is more important in gallbladder cancer than in bile duct cancer.

Adenocarcinoma↗
PubMed1995

Differential protective action of cytokines on radiation-induced apoptosis of peripheral lymphocyte subpopulations.

It is established that soluble factors involved in cell growth can prevent apoptosis of hematolymphoid cell lines in factor-deprived situations. The present study investigates the possible protective effects of various cytokines on radiation-induced apoptosis of apparently quiescent lymphocyte subpopulations. The exposure to gamma-irradiation resulted in appreciable apoptotic changes in all of lymphocyte subpopulations. Natural killer (NK) cells were the most radiosensitive, whereas CD8+ T and B cells showed weaker susceptibility to radiation and CD4+ T cells were relatively radioresistant. The radiation-induced apoptosis in NK cells was significantly inhibited by IL-2. In addition to IL-2, IL-4 and IL-7 rescued both CD4+ and CD8+ T cells from radiation-induced cell death. The viability of B cells was maintained by the presence of IL-4 but not others in culture. Furthermore, we conclude that the protective effect by each cytokine on radiation-induced apoptosis might be partly attributed to enhancement of cellular expression of bcl-2 protein.

Adult↗
PubMed1995

Interleukin-1 beta-stimulated prostaglandin synthesis by human decidual cells is independent of protein kinase C.

Basal prostaglandin E2 (PGE2) synthesis by human decidual cells was stimulated by phorbol myristate acetate (PMA) which activates protein kinase C. Staurosporine, which is an inhibitor of protein kinase C in most systems, also increased basal PGE2 synthesis. Further work is needed to explain this finding, as another inhibitor of protein kinase C, H7, inhibited PGE2 production under similar culture conditions. Interleukin-1 beta (IL-1 beta)-stimulated PGE2 synthesis was potentiated by coincubation with PMA or staurosporine, indicating that IL-1 beta and protein kinase C increase decidual PGE2 synthesis through different mechanisms. Desensitization of the decidual cells for 24 h with PMA did not affect IL-1 beta-stimulated PGE2 synthesis. The complex roles of protein kinase C in regulating decidual prostaglandin synthesis require further investigation, but it is clear that the effects of IL-1 beta are not mediated by protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Delineation of producing ability of IgG and IgA subclasses by naive B cells in newborn infants and adult individuals.

Neonatal B cells with the naive (sIgD+) phenotype are able to generate IgG- and IgA-producing cells as well as IgM production in the presence of memory CD4+ T cells expressing L-selectin (CD62L) in pokeweed mitogen-stimulated cultures. We used this system to examine comparatively the ability of naive B cells to produce IgG and IgA subclasses in newborn infants and adult individuals. Naive B cells were enriched from both donors on the basis of sIgD positivity, and memory (CD45RO+) CD4+ T cells with CD62L expression were isolated from adults. We here demonstrate some differences in profiles of IgG and IgA subclass production between neonatal and adult naive B cells. In neonatal B cells, IgG1 and IgG3 were predominantly produced, but IgG2 and IgG4 production was virtually absent. Similar to neonatal B cells, adult naive B cells produced mainly IgG1 and IgG3, although memory (sIgD-) B cells from adults secreted all of the IgG subclasses. It should be noted that low but detectable levels of IgG2 and IgG4 were found in adults' naive B cell cultures. Although IgA produced by neonatal B cells was exclusively IgA1, IgA2-secreting cells were identifiable in adult naive B cells. The results suggest that further class switch of naive B cells to IgG2, IgG4 and IgA2 in addition to IgG1 and IgG3 may be controlled by their own age-dependent maturation process.

Adult↗
PubMed1995

The possibility of clinical application of the thromboxane A2 synthase inhibitor, ozagrel, for the treatment and prevention of preeclampsia: a preliminary report.

OBJECTIVES: This study was performed to investigate whether the TXA2 synthase inhibitor, ozagrel, was effective in the treatment and prevention of pre-eclampsia. STUDY DESIGN: Ozagrel was administrated therapeutically to 4 severely pre-eclamptic women, and prophylactically to 5 pregnant women with histories of severe preeclampsia and complications. RESULTS: The therapeutic administration (TA) of ozagrel improved hypertension and proteinuria. Two patients delivered appropriate-for-date (AFD) infants, whereas the other 2 patients delivered light-for-date (LFD) infants. Mean plasma concentrations of TXB2 (plasma TXB2) decreased, whereas plasma 6-keto PGF1 alpha were almost unchanged. The prophylactic administration (PA) of ozagrel prevented the occurrence of preeclampsia in 3 of the 5 patients. All delivered AFD infants. The duration of pregnancy was prolonged more than that of previous pregnancies in all patients. Plasma TXB2 decreased, whereas plasma 6-keto PGF1 alpha increased. CONCLUSIONS: PA prevented preeclampsia and intrauterine growth retardation, whereas TA improved only maternal symptoms. These results might justify a large prospective study to determine whether ozagrel is an effective prophylactic.

Adult↗
PubMed1995

Effects of cervical spinal cord stimulation on glucose consumption in patients with posttraumatic prolonged unconsciousness.

The effects of cervical spinal cord stimulation (CSCS) on glucose consumption were examined in two patients with prolonged disturbance of consciousness due to head injuries. Several clinical parameters, including glucose consumption using positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose (FDG), were compared before and after CSCS. After a 4-month period of stimulation, one patient (Case 1) regained consciousness and began to speak, but the other patient (Case 2) showed no improvement in consciousness level. Computed tomography and magnetic resonance imaging showed Case 1 had no abnormalities in the thalamus and brainstem and no diffuse brain atrophy. Case 2 had a low density area in the left thalamus and enlargement of the aqueduct with diffuse atrophy of the left cerebral hemisphere. Cerebral blood flow studies and electrophysiological examinations revealed no remarkable change after CSCS. The PET study showed an increase in FDG uptake in the hypothalamus and the thalamus in both patients, but an increase in FDG uptake in the left cingulate gyrus and left frontal lobe was observed only in Case 1. These observations suggest that activation of the ascending reticular activating system, hypothalamus, thalamus, cingulate gyrus, and frontal cortex, and the preservation of the fiber connections between the limbic system and the thalamus and hypothalamus are important for CSCS treatment to improve the level of consciousness.

Adolescent↗
PubMed1995

Metabolism of gemcitabine in rat and dog.

1. The metabolism of 14C-gemcitabine in the male rat has been studied after intravenous administration of a single dose (10 mg/kg) or five doses (1 mg/kg/day) of 14C-gemcitabine. The metabolism in male dog has been studied after only single dosing. The effects of gemcitabine on hepatic drug-metabolizing enzymes in rat has also been studied. 2. The concentration of gemcitabine in the plasma was 11.84 micrograms/ml at 5 min, and then rapidly decreased after a single administration to rat. A deaminated uracil analogue of gemcitabine progressively increased with time. Gemcitabine and the uracil metabolite accounted for 80.0 and 11.8% of the radioactive dose in the 0-24-h urine samples respectively. Gemcitabine was the major component identified in lung, liver and kidney at 5 min after administration. 3. After repeated administration to rat, metabolites in the plasma and tissues were not remarkably different from those found after a single administration. 4. After a single administration to dog, the plasma concentration of gemcitabine was 12.39 micrograms/ml at 5 min. Gemcitabine and the uracil metabolite accounted for 8.3 and 71.8% of the dose in the 0-24-h urine samples respectively. 5. No differences were observed in enzymatic activities per whole liver between the gemcitabine-treated and control rat.

Animals↗
PubMed1995

Deterioration of mechanical properties of composite resins.

The deterioration of the mechanical properties of composite resins was examined. The bending strength and the stress relaxation rate for sixteen experimental composite resins with different filler shapes, particle sizes and filler contents immersed in distilled water for 0-60 days were measured. The bending strength of all of the composites decreased with the increase of the immersion time in water. The composites with a high filler content (65 vol%) showed a greater decreasing ratio of bending strength than those with low filler content (40 vol%). The stress relaxation rate also increased with and increase of immersion time. The phenomena may be caused by the hydrolytic degradation of the silane coupling agent (gamma-MPTMS).

Bisphenol A-Glycidyl Methacrylate↗
PubMed1995

[Expression of proliferating cell nuclear antigen (PCNA) in renal cell carcinoma].

PURPOSE: The objective of this study is to evaluate the relationship among PCNA positive ratio, pathological findings, nuclear DNA contents, and prognosis in renal cell carcinoma. Immunohistochemical analysis using the monoclonal antibody of PCNA were performed on a total number of 151 formalin-fixed paraffin-embedded samples (1-7 samples with a mean of 3.8) from 40 renal cell carcinomas. The percentage of PCNA positive cancer cells to the total amount of cancer cells was expressed as labeling index (LI; %). By means of flow cytometry we analysed nuclear DNA contents from the same samples. RESULTS: 1) LIes in pathological grades were 2.79 +/- 3.33% (mean +/- SD) for grade 1 (n = 16), 5.63 +/- 4.08% for grade 2 (n = 20), and 9.95 +/- 4.59% for grade 3 (n = 4). There was significant difference between grade 1 and grade 3 (p < 0.05). 2) LIes in pathological stage were 3.22 +/- 3.05% for pT2 (n = 22) and 7.01 +/- 4.99% for pT3 and pT4 (n = 18) (p < 0.05). 3) There was no significant correlation between LI and lymph node involvement. And there was no significant correlation between LI and distant metastasis, either. 4) LIes in nuclear DNA contents were 2.41 +/- 3.14% for DNA diploid (n = 17) and 6.80 +/- 4.29% for DNA aneuploid (n = 23) (p < 0.05). 5) It was suggested that LI was shown to vary according to the parts in a given tumor examined in parallel with tumor heterogeneity of nuclear DNA content. 6) The 5-year cause-specific survival rate of the patients with LI > or = 5.0% (n = 15) was 40%, while that with LI < 5.0% was 74% (n = 25) (p < 0.05). CONCLUSION: These findings suggest that LI, which was determined by immunohistochemical analysis using PCNA antibody indicates a growth potential of renal cell carcinoma and is available for estimating malignant potential.

Adult↗
PubMed1995

[A case of duodenal duplication and a review of reported cases].

We report a case of duodenal duplication and review of literatures on 43 cases reported in Japan including ours. A 34-year-old female who was admitted with chief complaints of epigastric pain and hematoemesis. An endoscopic examination and a hypotonic duodenography revealed a protruding tumor with bleeding ulcer. Wedge resection of the duodenum, including the lesion, was performed. A diagnosis of duodenal duplication was made by histopathological examination.

Adult↗
PubMed1994

Differential expression of bcl-2 and susceptibility to anti-Fas-mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils.

The recently identified Fas antigen (Ag) is a cell surface molecule that can mediate apoptosis. The cytoplasmic product of proto-oncogene bcl-2 has been shown to prolong the cellular survival by inhibiting apoptosis. To elucidate the physiologic significance of expression of both molecules, we examined the expression of Fas Ag and bcl-2 on blood leukocyte populations and evaluated their sensitivity to the cytolytic action of anti-Fas antibody. Although Fas Ag was expressed on a fraction of lymphocytes, both neutrophils and monocytes expressed Fas Ag constitutively. In contrast, there was marked difference among these leukocytes regarding bcl-2 expression. Lymphocytes expressed bcl-2 intensely, but monocytes showed weaker bcl-2 expression, and neutrophils were essentially absent for bcl-2 expression. Seemingly reflecting this lack of bcl-2-expression, neutrophils more easily underwent apoptotic cell death in vitro as compared with monocytes and lymphocytes. We showed that anti-Fas antibody affectively accelerated apoptotic cell death in neutrophils. However, the apoptosis-inducing effect of anti-Fas antibody was minimal on monocytes, and lymphocytes were resistant to this antibody. These results suggest that anti-Fas-mediated cell death may, in part, be determined by bcl-2 expression status in Fas+ lymphoid and hematopoietic cells.

Adult↗
PubMed1994

Efficient induction of immunoglobulin production in neonatal naive B cells by memory CD4+ T cell subset expressing homing receptor L-selectin.

The humoral response in newborns is mainly restricted to IgM production, which may be attributable to the naive nature of both B and T cells at birth. In light of the current evidence that memory (CD45RO+) CD4+ T cells help B cell differentiation, the present study was undertaken to examine whether a specified population within memory CD4+ T cells could induce the maturation of neonatal naive B cells. In the conventional PWM-stimulated cultures, the generation of IgG- and IgA-producing cells in addition to IgM production by neonatal B cells was significantly enhanced by co-cultures with memory, but not naive, CD4+ T cells. Memory CD4+ T cells were further divided into two populations based on expression of homing receptor L-selectin. These memory CD4+ T cell subpopulations appeared to behave in different fashions concerning help for Ig production by naive (sIgD+) and mature (sIgD-) B cells. L-selectin-negative memory CD4+ T cells exhibited helper function for Ig secretion by mature B cells. Intriguingly, Ig production by neonatal B cells as well as adult naive B cells, although less than that by mature B cells, was efficiently promoted by L-selectin-positive memory CD4+ T cells rather than L-selectin-negative ones. The results suggest that the capability of neonatal naive B cells to secrete IgG and IgA can be elicited by appropriate T-cell signals, especially from the L-selectin-positive population within memory CD4+ T cells, seemingly indicating its possible role for isotype switching in B cells.

Adult↗
PubMed1994

Ionizing radiation induces apoptotic cell death in human TcR-gamma/delta+ T and natural killer cells without detectable p53 protein.

The p53 tumor suppressor gene has been shown to be involved in programmed cell death, apoptosis, in murine immature thymocytes after treatment with ionizing radiation. Ionizing radiation also induces apoptosis in peripheral mature lymphocytes. In this work, we investigated the p53 participation in radiation-induced apoptosis in human peripheral blood lymphocytes (PBL) subpopulations. Exposure to gamma-irradiation resulted in an appreciable induction of apoptotic cell death in TcR-alpha/beta+ (CD4+ and CD8+) T cells, TcR-gamma/delta+ T cells, B cells and natural killer (NK) cells, as assessed by DNA fragmentation as well as the morphological characteristics. Importantly, it was found that there was a marked difference among PBL subpopulations as regards the induction of p53 protein by gamma-irradiation. Similar to previous observations for murine thymocytes, p53 induction in TcR-alpha/beta+ T cells and B cells after gamma-irradiation was evident by Western blot analysis. Radiation-induced apoptosis in TcR-alpha/beta+ T cells and B cells was efficiently inhibited by cycloheximide, indicating the requirement of de novo protein synthesis, including p53 protein, for radiation-induced apoptosis in both subpopulations. In marked contrast, no identifiable levels of p53 protein were induced in either TcR-gamma/delta+ T or NK cells after gamma-irradiation. In addition, it was demonstrated that radiation-induced cell death in TcR-gamma/delta+ T and NK cells could be prevented by interleukin-2, but not by cycloheximide. These results imply that radiation-induced lymphocytic apoptosis can be mediated by p53-dependent or -independent mechanisms.

Adult↗
PubMed1994

Synthesis and in vivo evaluation of [11C]semotiadil, a benzothiazine calcium antagonist.

A carbon-11 labeled benzothiazine calcium antagonist, (+)-(R)-2-[5-methoxy-2-[3-[methyl[2-[(3,4- methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-2H-1,4- benzothiazin-3(4H)-one (semotiadil), and its enantiomer were prepared by N-methylation of the corresponding norderivatives with 11CH3I: decay-corrected radiochemical yields of 16-27% based on 11CH3I, radiochemical, chemical and optical purity of > 99%, sp. act. of 11-50 GBq/mumol and preparation time of 35-40 min. In mice, saturable and stereo-selective uptake in the hippocampus, striatum and hypothalamus was observed. The potential of the compound to visualize the regional brain calcium channels in vivo by positron emission tomography was indicated; however, no promising sign was found in the myocardium.

Animals↗