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K Koide

Publications and source records attributed to K Koide.

At least 37 records · Page 2Linked to original sources
PubMed1997

Interleukin-18 activates NF-kappaB in murine T helper type 1 cells.

Interleukin-18 (IL-18) activated T helper type 1 (Th1) cells, OVA#4, and induced production of interleukin-2 (IL-2) in costimulation with anti-CD3 antibody. Upon stimulation with IL-18, IkappaB disappeared from cytoplasm and subsequently nuclear factor-kappaB (NF-kappaB) (p65) accumulated in the nucleus. Corresponding with that, DNA binding activity of NF-kappaB (p65 homodimer or p65/p50 heterodimer) was detected in the nucleus. In the transfection experiments, an IL-2 promoter-driven reporter construct showed the similar responsiveness against IL-18 to that of the intrinsic IL-2 gene, and a construct lacking kappaB site failed to respond to IL-18. These results suggest that IL-18 activates NF-kappaB and it is important for enhancement of IL-2 gene expression by Th1 cells stimulated with IL-18.

Animals↗
PubMed1997

Increased apoptosis rate by hyperthermochemoradiotherapy for advanced rectal cancers.

Apoptosis induced in cancer cells by ionizing radiation, hyperthermia, and 5-fluorouracil (5-FU), termed "hyperthermochemoradiotherapy" (HCR), has been well studied in vitro; however, the role of apoptosis in the tumocidal effect of HCR for primary rectal cancers has not yet been clarified. Therefore, we examined the relationship between the therapeutic effect and induction rate of histological apoptosis in 16 patients with rectal cancers after HCR. Numerous Tunel-positive apoptotic cells were found in the tumor tissue after HCR, but few were found in the tumors which had not received HCR. The histological therapeutic effect was closely correlated to the rate of apoptosis. Thus, we suggest that HCR induces a therapeutic effect mainly through apoptosis in human rectal cancers.

Administration, Rectal↗
PubMed1997

Plasma levels of leukotriene E4 during clinical course of chronic obstructive pulmonary disease.

We investigated the relationship between circulating leukotriene E4 (LTE4) and chronic obstructive pulmonary disease (COPD) by measuring plasma levels of leukotriene E4 in patients with COPD and 10 normal controls. We also investigated the relationship between LTE4 levels and FEV1 and PaO2. Leukotriene E4 was measured by high performance liquid chromatography (HPLC) and radioimmunoassay. The mean leukotriene E4 level in patients with COPD during remission, during acute exacerbation before and after prednisolone treatment were 16.8[4.02], 41.7[21.9], and 19.5[3.78] pg/ml (mean[SD]), respectively. In contrast, the mean leukotriene E4 level of 10 normal controls was 11.8[4.49] pg/ml. Thus, the mean LTE4 level during an acute exacerbation of COPD was significantly lower in patients after prednisolone treatment than in patients before prednisolone treatment. The mean LTE4 level in patients after prednisolone treatment did not significantly differ from that in patients during remission and in normal controls (Scheffe F-test, P < 0.05) (Fig. 1). Mean FEV1 (% predict) values were 51.4[9.02] (mean[SD]), 38.0[4.82], and 44.2[4.48] on the three occasions, respectively; corresponding mean PaO2 values (mmHg) were 84.0[5.01] (mean[SD]), 61.3[1.66], and 80.6[5.30], respectively. Leukotriene E4 levels were significantly correlated with PaO2 and relatively with FEV1 in the patients during acute exacerbation before prednisolone treatment. Thus, we suggest that leukotriene E4 levels in arterial blood reflect the severity of COPD lung and oral prednisolone reduces the plasma levels of leukotriene E4 in patients with COPD.

Adult↗
PubMed1997

Effect of azelastine hydrochloride on release and production of platelet activating factor in human neutrophils.

Effect of azelastine hydrochloride (azelastine) on release and production of platelet-activating factor (PAF) in neutrophils obtained from asthmatic and non-asthmatic patients was investigated. Neutrophils were preincubated with or without azelastine and stimulated with f-Met-Leu-Phe (fMLP, 10 microM) for 15 min. PAF-like activity was detected by aggregation of washed guinea pig platelets. PAF-like activity released from asthmatic neutrophils without preincubation of azelastine was 5.67[0.89] (mean[SD], ng/10(7) cells) in supernatants and 21.8[0.76] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of azelastine, PAF-like activity reduced to 5.96[0.97] (mean[SD], ng/10(7) cells), 3.49[0.63], and 1.89[0.09] (n = 15) in the supernatants, and 20.7[0.97], 13.9[0.29], and 8.91 [0.99] (n = 15) in the cell pellets, respectively. PAF-like activity in non-asthmatic neutrophils without preincubation of azelastine was 4.67[0.19] (mean[SD], ng/10(7) cells) in supernatants and 18.5[0.34] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of azelastine, PAF-like activity reduced to 4.39[0.51] (mean[SD], ng/10(7) cells), 2.77[0.22], and 1.75[0.07] (n = 15) in the supernatants, and 17.9[0.54], 10.8[0.25], and 5.97 [0.59] (n = 15) in the cell pellets, respectively. Our results showed that preincubation with azelastine caused a dose-dependent inhibition of intra and extracellular PAF-like activity from asthmatic and non-asthmatic neutrophils in the same manner.

Asthma↗
PubMed1997

Enhancement of leukotriene B4 release in stimulated asthmatic neutrophils by platelet activating factor.

BACKGROUND: The role of platelet activating factor (PAF) in asthma remains controversial. The priming effect of PAF on leukotriene B4 (LTB4) release, 5-lipoxygenase activity, and intracellular calcium levels in asthmatic neutrophils was examined. METHODS: LTB4 and other lipoxygenase metabolites in neutrophils obtained from 17 asthmatic patients and 15 control subjects were measured by reverse phase-high performance liquid chromatography (RP-HPLC). Intracellular calcium levels were monitored using the fluorescent probe fura-2. RESULTS: The mean (SD) basal LTB4, release from neutrophils was not significantly different between the two groups (0.05 (0.01) vs 0.03 (0.02) ng/10(6) cells); however, when stimulated with calcium ionophore A23187 (2.5 microM), neutrophils from asthma patients released more LTB4 than cells from control subjects (15.7 (1.2) vs 9.9 (1.6) ng/10(6) cells). Although PAF alone did not alter LTB4 release, it enhanced the response to subsequent A23187 stimulation. This effect was observed following treatment for five minutes with PAF at concentrations > 1.0 microM. The maximal effect was seen with 5.0 microM PAF + 2.5 microM A23187 (62.7 (2.2) vs 18.6 (2.3) ng/10(6) cells). Pretreatment with PAF also increased 5-lipoxygenase activity and intracellular calcium levels in neutrophils from asthmatic patients to a greater extent than in those from non-asthmatic patients. CONCLUSIONS: These findings indicate that, in neutrophils from asthmatic patients, PAF enhances LTB4 release and increases 5-lipoxygenase activity and intracellular calcium to a greater extent than in neutrophils from non-asthmatic patients.

Adult↗
PubMed1997

[Histopathological study in models of chronic pancreatitis].

UNLABELLED: Histopathological findings were examined in the models of chronic pancreatitis. Using mongrel dogs, we prepared a control group (group C), a chronic ischemic group (group I), an alcohol administration group (group A), a duct obstruction group (group O), and an alcohol + obstruction group (group AO). Group I showed severe inflammatory cell infiltration, fibrosis, fat replacement and loss of acinar cells. Group A showed no change. In group O, mild periductal fibrosis was recognized. Group AO showed moderate inter-lobular fibrosis and inflammatory cell infiltration, resembling those of human chronic alcoholic pancreatitis. CONCLUSION: 1) Histological findings of chronic ischemic group is severer than that of group O and AO. 2) The model of alcohol administration with incomplete duct obstruction is a useful model of human chronic alcoholic pancreatitis.

Animals↗
PubMed1997

[The risk of palliative operation for bone metastasis].

Palliative operations for various bone metastases are being performed more frequently than before with the improvement of surgical technique and the development of new instruments. However, anesthesia in advanced cancer patients who are under palliative care accompanies inherent risks which are uncommon in general orthopaedic populations. Thus, we made a retrospective analysis of the medical records of 59 patients scheduled for palliative operation against metastatic bone lesions during the last 4 years. The survey revealed 5 cases of perioperative lethal events. Two of them died preoperatively from the hepatic failure and unexpected cerebral tumor embolism. An intraoperative cardiac arrest secondary to pulmonary embolism occurred in a patient during intramedullary nailing. There was a patient who developed disseminated intravascular coagulation and acute renal failure after posterior fixation of the lumbar vertebrae. The remaining one patient with superior vena cava syndrome developed life-threatening airway obstruction during general anesthesia with endotracheal intubation. We conclude that the exact evaluation of the patient's condition and the careful management of vital organ functions are mandatory during the perioperative period. In this regard, the anesthesiologists should be involved not only in the intraoperative anesthetic management but also in the perioperative care of the patients with bone metastasis.

Adult↗
PubMed1996

In vivo effect of prednisolone on release of leukotriene B4 from neutrophils from asthmatic patients.

We examined the release of leukotriene B4 from calcium ionophore A23187-stimulated neutrophils from asthmatic patients treated with or without intravenous prednisolone during an asthmatic attack. The mean level of LTB4 in the supernatant of stimulated neutrophils from patients treated with intravenous prednisolone was significantly lower than that in the supernatant of stimulated neutrophils from those without prednisolone treatment. Preincubation with prednisolone caused a dose-dependent inhibition of LTB4 release from calcium ionophore A23187-stimulated neutrophils. These findings suggest that intravenous prednisolone inhibits the release of LTB4 from neutrophils in vivo.

Adult↗
PubMed1996

Priming effect of platelet activating factor on leukotriene C4 from stimulated eosinophils of asthmatic patients.

BACKGROUND: Eosinophils from asthmatic patients are known to release greater amounts of leukotrienes than normal eosinophils when stimulated by the calcium ionophore A23187. The effect of platelet activating factor (PAF) in priming eosinophils was investigated. METHODS: Eosinophils were obtained from 18 asthmatic patients and 18 healthy donors. Cells separated by the Percoll gradients were incubated with PAF (C-18) for 30 minutes and then stimulated with the calcium ionophore A23187 (2.5 microM) for 15 minutes. The amount of leukotriene C4 (LTC4) in supernatants was measured using a combination of high pressure liquid chromatography and radioimmunoassay. RESULTS: The mean (SD) amount of LTC4 released by eosinophils from asthmatic patients upon stimulation with the calcium ionophore A23187 alone was 27.9 (9.9) ng/10(6) cells (n = 6). The amount of LTC4 released following stimulation with the calcium ionophore A23187 after pretreatment with PAF (1, 5, and 10 microM) was 57.2 (8.9), 75.1 (14.3), and 52.6 (10.7) ng/10(6) cells (n = 6), respectively. Trace amounts of LTC4 (0.9 (0.02) ng/10(6) cells, n = 6) were detected in the supernatant of the cells after stimulation by PAF alone (5 microM). The amount of LTC4 released upon stimulation by calcium ionophore A23187 alone in eosinophils from healthy donors was 10.3 (3.7) ng/10(6) cells (n = 4). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with PAF at concentrations of 1, 5, and 10 microM were 11.9 (3.5), 17.8 (5.6), and 12.7 (5.1) ng/10(6) cells (n = 4), respectively. Trace amounts of LTC4 (0.6 (0.02) ng/10(6) cells, n = 4) were detected in the supernatant of the cells upon stimulation with PAF alone (5 microM). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with lyso-PAF at concentrations of 1, 5, and 10 microM (n = 4 or 6) were 30.8 (5.2), 22.9 (5.1), and 27.3 (4.3) ng/10(6) cells (n = 6) from the eosinophils of asthmatic patients and 13.7 (3.3), 15.2 (4.9), and 14.7 (3.8) ng/10(6) cells (n = 4) from the eosinophils of healthy donors. CONCLUSIONS: The results indicated that PAF enhanced LTC4 formation by eosinophils obtained from asthmatic patients stimulated with the calcium ionophore A23187, but not those obtained from normal subjects.

Adult↗
PubMed1996

Alteration of bile acid metabolism by cimetidine in healthy humans.

BACKGROUND: To clarify an effect of cimetidine on bile acid metabolism, we evaluated whether an increased deconjugation of bile acids would occur in healthy humans who have received cimetidine. We examined: 1) whether healthy volunteers taking cimetidine would have positive bile acid breath tests because of bacterial overgrowth in the jejunum; 2) whether the isolated bacteria would exhibit deconjugation ability; and 3) whether a change in gastric pH was related to the bacterial overgrowth. METHODS: We evaluated 73 healthy Japanese volunteers; 53 of them received cimetidine and 20 did not. Deconjugation of bile acids was detected as 14CO2 specific activity of expired air measured by a bile acid breath test giving 5 muCi of oral glycine-1-(14)C labeled glycocholate. Aspiration of jejunal fluids was performed by a double lumen tube with a rubber cover on the tip, and deconjugation ability of bacteria was evaluated using thin layer chromotography. RESULTS: Samples of expired breath from the 53 healthy volunteers showed a significant increase in 14CO2 specific activity after the administration of cimetidine rather than before the administration of cimetidine. Bacterial over-growth was found in the jejunal fluid after the administration of cimetidine. The administration of tetracycline to 27 subjects significantly reduced the 14CO2 specific activity. The following species were identified in the jejunal fluid samples obtained from the subjects: enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, B uniformis, Eubacterium lentum, E parvum, and Escherichia coli. Except for E coli, all of the bacterial species identified deconjugated bile acids. We observed a significant relationship between 14CO2's specific activity and gastric pH before and after administration of cimetidine, respectively. CONCLUSIONS: Healthy volunteers who received cimetidine showed an increased deconjugation of bile acid caused by overgrowth of bacteria in the jejunum, which can deconjugate bile acids. The bacterial overgrowth is probably associated with a shift to neutral pH in the gastric juice caused by cimetidine.

Adult↗
PubMed1995

In vivo effect of prednisolone on release of leukotriene C4 in eosinophils obtained from asthmatic patients.

We investigated the release of leukotriene C4 from eosinophils of asthmatic patients who were treated with or without intravenous prednisolone. The mean level of LTC4 in the supernatant of A23187-stimulated eosinophils obtained from asthmatic patients during an attack was significantly lower with intravenous prednisolone than without prednisolone treatment. Findings suggest that intravenous prednisolone inhibits the release of LTC4 from the eosinophils of asthmatic patients by acting on these cells in vivo.

Adult↗
PubMed1995

Molecular design and biological activity of potent and selective protein kinase inhibitors related to balanol.

BACKGROUND: The protein kinase C (PKC) family of serine/threonine-specific protein kinases is involved in many cellular processes, and the unregulated activation of PKC has been implicated in carcinogenesis. PKC inhibitors thus have significant potential as chemotherapeutic agents. Recently, the fungal metabolite balanol was shown to be an exceptionally potent inhibitor of PKC. We previously developed a practical and efficient total synthesis of balanol. We set out to use this synthetic molecule, and several synthetic analogs, to probe the mechanism of PKC inhibition and to determine the effect of balanol on the activity of other protein kinases. RESULTS: As well as inhibiting PKC, balanol is a potent inhibitor of cyclic AMP-dependent protein kinase (PKA), another protein serine/threonine kinase. Balanol does not, however, inhibit the Src or epidermal growth factor receptor protein tyrosine kinases. The inhibition of both PKC and PKA by balanol can be overcome by high concentrations of ATP, and molecular modeling studies suggest that balanol may function as an ATP structural analog. Although balanol discriminates rather poorly between PKC and PKA, only minor modifications to its molecular structure are required to furnish compounds that are highly specific inhibitors of PKA. CONCLUSIONS: A number of balanol analogs have been designed and synthesized that, unlike balanol itself, exhibit dramatic selectivity between PKA and PKC. Thus, despite the substantial homology between the catalytic domains of PKA and PKC, there is enough difference to allow for the development of potent and selective inhibitors acting in this region. These inhibitors should be useful tools for analyzing signal transduction pathways and may also aid in the development of drugs with significant therapeutic potential.

Adenosine Triphosphate↗