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Yutaka Komiyama

Publications and source records attributed to Yutaka Komiyama.

At least 19 recordsLinked to original sources
PubMed2006

Novel digitalis-like factor, marinobufotoxin, isolated from cultured Y-1 cells, and its hypertensive effect in rats.

Marinobufagenin and telecinobufagin have been identified as digitalis-like factors in mammals. In toads, marinobufagenin-related compounds, such as marinobufotoxin (MBT), have been isolated in some tissues but not in mammals, and its biological action has not been elucidated. Herein, we aimed to explore the possible production and/or secretion of MBT and the biological action in rats. First, the MBT in culture supernatant of the adrenocortical-originated cell line Y-1 was analyzed by high-performance liquid chromatography and sensitive ELISA for marinobufagenin-like immunoreactivity. Moreover, the structural information was obtained by mass spectrometry. To determine the biological action, MBT (9.6 and 0.96 microg/kg per day) was intraperitoneally infused via an osmotic minipump for 1 week. Blood pressure and renal excretion of marinobufagenin-like immunoreactivity were measured. Marinobufagenin-like immunoreactivity was found in Y-1 cell culture media, and the concentration increased until 24 hours. The structural analysis suggested that marinobufagenin-like immunoreactivities were marinobufagenin and MBT, and tandem mass spectrum analysis revealed them with the specific daughter ions. The highest sensitive ELISA-positive peak of marinobufagenin-like immunoreactivity in the media was MBT. Continuous administration of MBT in rats for 1 week significantly increased systolic blood pressure and renal excretion of marinobufagenin-like immunoreactivity compared with control rats (135+/-3.0 versus 126+/-2.0 mm Hg and 1.41+/-0.286 versus 0.34+/-0.064 ng/day, respectively). These data suggest that MBT, arginine-suberoyl ester of marinobufagenin, can be a novel digitalis-like factor with hypertensive action and is secreted from the adrenocortical cells.

Adrenal Cortex↗
PubMed2006

Elevation of soluble interleukin-2 receptor in patients with non-small cell lung cancer treated with gefitinib.

PURPOSE: We previously reported that plasma thromboxan B(2), soluble P-selectin, and serum regulated on activation, normal T-cell expressed and secreted (RANTES) were elevated after gefitinib treatment. We hypothesized that gefitinib could activate T-lymphocytes via activated platelets, and so we measured serum levels of soluble interleukin-2 receptor (sIL-2R) in patients medicated with gefitinib. METHODS: Twenty-one patients with non-small cell lung cancer (NSCLC) were entered into this study. All patients received gefitinib over 2 weeks without severe adverse effects. Blood samples were withdrawn from all patients before and after the administration of gefitinib and plasma soluble P-selectin, serum RANTES, and serum sIL-2R were measured by enzyme-linked immunosolvent assay. In addition, we carried out the basic study of the interleukin-2 receptor (IL-2R) expression on CD4(+) lymphocytes by RANTES. RESULTS: Plasma soluble P-selectin, serum RANTES, and serum sIL-2R levels increased significantly in patients receiving gefitinib treatment for 1 and 2 weeks. RANTES did not induce the expression of IL-2R on CD4(+) lymphocyte. However, the anti-CD3 monoclonal antibody-induced expression of IL-2R was enhanced by the addition of RANTES. CONCLUSION: Our finding indicated that lymphocytes were activated by gefitinib treatment. We think that sIL-2R elevation after gefitinib administration may be a factor positively effecting patients with NSCLC. It is deemed possible that the effect of gefitinib is induced not only by its blocking of the tyrosine kinase of epidermal growth factor receptor but also by antitumor immunity via its activation of T-cells.

Adult↗
PubMed2006

IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis.

IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17(-/-) murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17(-/-) mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17(-/-) mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of IL-17(-/-) CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL-17-producing T cells were increased in IFN-gamma(-/-) cells, while IFN-gamma-producing cells were increased in IL-17(-/-) cells, suggesting that IL-17 and IFN-gamma mutually regulate IFN-gamma and IL-17 production. These observations indicate that IL-17 rather than IFN-gamma plays a crucial role in the development of EAE.

Adoptive Transfer↗
PubMed2006

Aspirin reduces adverse effects of gefitinib.

We measured serum levels of soluble (s) P-selectin and thromboxane B2 (TxB2) in patients with lung cancer treated with gefitinib, and investigated the effect of low-dose aspirin on some adverse effects of gefitinib. The serum levels of sP-selectin and TxB2 increased significantly in all patients who received gefitinib for 2 weeks. Forty patients were recruited, and 28 received gefitinib without low-dose aspirin (Group 1) and 12 were co-administered low-dose aspirin (Group 2). In Group 2, the frequency of adverse events, skin rash and diarrhea was evidently reduced by the low-dose aspirin therapy, despite having shown no remarkable change in gefitinib responsiveness between both groups. In one of the 12 patients in Group 2, aspirin therapy was suspended due to the occurrence of nasal bleeding. Four days after treatment suspension, she developed a skin lesion in her finger. However, the skin lesion improved after re-administration of aspirin without any other medications. After treatment, TxB2 significantly decreased, but not sP-selectin. These results suggest that one of the mechanisms causing gefitinib-related adverse effects depends on platelet activation. Administration of gefitinib with low-dose aspirin to lung cancer patients may prevent the development of gefitinib-related complications.

Adult↗
PubMed2006

Clinical monitoring of innate cellular immunity of monocytes/macrophages by tumor necrosis factor alpha productivity in whole blood stimulated by lipopolysaccharide in patients with pancreatic cancer.

OBJECTIVE: The aim of this study was to evaluate the tumor necrosis factor alpha (TNF-alpha) releasing capacity in whole blood stimulated by lipopolysaccharide (LPS) in patients with pancreatic cancer during the perioperative period, and before and after chemotherapy. METHODS: The current study involved a total of 39 patients with pancreatic cancer (PC), who were further divided into a PC-Op group (n = 16, underwent pancreatectomy) and a PC-chemo group (n = 23, received chemotherapy). The control groups consisted of patients with hepatocellular carcinoma (n = 27, HCC group) and with benign diseases (n = 15, control group). Serial changes in TNF-alpha in whole blood stimulated by LPS were compared in various clinical settings. RESULTS: Preoperative TNF-alpha levels in the PC-Op group were significantly lower than those in the HCC and control groups (P = 0.034). The TNF-alpha variable surgical index (s-index) was defined as the ratio of the preoperative TNF-alpha level to postoperative level in the PC-Op and HCC groups. Although the TNF-alpha s-index in the PC-Op group was significantly decreased on postoperative day 1 and recovered on postoperative day 3 (P < 0.002), there were no significant changes in the TNF-alpha s-index in the HCC group. The TNF-alpha variable chemotherapeutic index (c-index) was defined as the ratio of the TNF-alpha level before to that after chemotherapy in the PC-chemo group. The TNF-alpha c-index in all 7 patients was reduced to less than 0.3 until leukopenia appeared. Patients who had an increase in TNF-alpha production (TNF-alpha c-index >1.0) on day 3 or 7 after chemotherapy had significantly better cumulative survival than those with no increase (P < 0.033). CONCLUSIONS: TNF-alpha production stimulated by LPS in the whole blood of patients with pancreatic cancer was low. Surgical stress and depressed immunocompetence might induce such profound decreases. A method of assessing the capability of leukocytes, particularly macrophages, to produce TNF-alpha could be useful for prognostis and for monitoring immunocompetence in patients with pancreatic cancer who have undergone chemotherapy.

Adult↗
PubMed2005

Increased soluble FcgammaRIIIa(Mphi) in plasma from patients with coronary artery diseases.

Atherosclerosis is the underlying disease process in patients affected with coronary artery diseases (CAD). Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express Fcgamma receptor type IIIa (FcgammaRIIIa: CD16) identical to that in natural killer cells (NK cells), but with a cell type-specific glycosylation. In contrast, neutrophils express FcgammaRIIIb. These FcgammaRIIIs are released from the cell surface on activation, and these soluble forms (sFcgammaRIII) are present in the plasma. We measured sFcgammaRIIIa(Mphi) in the plasma with a newly developed anti-FcgammaRIII mAb, MKGR14, which recognizes FcgammaRIIIa(Mphi) specifically. The level of sFcgammaRIIIa(Mphi), as well as the level of sFcgammaRIIIa (sFcgammaRIIIa(Mphi) plus sFcgammaRIIIa(NK)) or the level of total sFcgammaRIII (sFcgammaRIIIa plus sFcgammaRIIIb), were significantly increased in patients with CAD, but not in patients with vasospastic angina (VSA) or intact coronary arteries, compared with age-matched healthy donors. The sFcgammaRIIIa(Mphi) level was related to the number of significantly affected coronary arteries, and positively correlated with LDL-cholesterol to HDL-cholesterol ratios, but negatively with HDL-cholesterol. No correlation among the levels of three sFcgammaRIIIs was observed in CAD patients, as well as in healthy donors. The macrophages are activated during the process of atherosclerosis, and sFcgammaRIIIa(Mphi) may serve as a novel marker for atherosclerosis.

Aged↗
PubMed2005

Polymorphism of Fc gamma RIIa may affect the efficacy of gamma-globulin therapy in Kawasaki disease.

We evaluated whether there is a possible relationship between the effectiveness of gamma-globulin treatment for patients with Kawasaki disease (KD) and the polymorphism of Fcgamma RIIa, IIIb, and IIIa. Genomic DNA was extracted from whole blood collected from 56 patients with KD who received gamma-globulin treatment. The genotypes for Fcgamma RIIIb-NA(1, 2), Fcgamma RIIa-H/R131, and FcgammaRIIIa-F/V158 were determined to investigate the association between these polymorphisms and the development of coronary lesions (CALs). Twenty-three percent of patients with the HH allele for the Fcgamma RIIa polymorphism progressed to CALs, compared with 60% with the HR and RR alleles. HR and RR alleles may be a predictor of the progression of CALs in KD before the initiation of gamma-globulin therapy.

Antigens, CD↗
PubMed2005

A novel endogenous digitalis, telocinobufagin, exhibits elevated plasma levels in patients with terminal renal failure.

BACKGROUND AND OBJECTIVES: There are several potential endogenous digitalis-like factors (EDLF) in mammalian body fluids, and marinobufagenin (MBG) may be the most potent EDLF. Improved assays are needed to confirm the potency of these metabolites. In the present study, we have identified MBG and telocinobufagin (TCB) in human plasma by high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR). METHODS AND RESULTS: The high-resolution MS analysis revealed the molecular masses of TCB and MBG to be the same as their respective theoretical values. Using a tandem mass spectrometer, the mass-charge ratio for TCB was determined to be 403.2 for the parent ion and 349.2 for the daughter ion. The mass-charge ratio for MBG was m/z 383.2 and m/z 401.2. The NMR study revealed that the signals for MBG and TCB were the same as those obtained by MS analysis. In human blood, MBG and TCB were also identified by liquid chromatography (LC) as well as MS. In the LC/MS assay, proscillaridin A was used as an internal standard. The plasma was pretreated with Sep-Pak C18, and then 50 microL was applied to the C8 high-performance liquid chromatography (HPLC) column. The mean plasma concentration of MBG in healthy volunteers (0.94 +/- 0.28 ng/mL) was significantly lower than that in patients undergoing regular hemodialysis (3.81 +/- 1.92 ng/mL). The concentration of TCB in the healthy volunteers (1.80 +/- 0.55 ng/mL) was also significantly lower than that in patients with terminal renal failure (6.86 +/- 4.30 ng/mL). CONCLUSION: These results indicate that the major EDLF is TCB because its plasma concentration is the highest among the reported endogenous digitalis candidates.

Bufanolides↗
PubMed2005

Gefitinib affects functions of platelets and blood vessels via changes in prostanoids balance.

Prostaglandins (PGs) and thromboxane (TX) produced by cyclooxygenase (COX) have a great influence on vascular systems and platelet functions. The serum levels of epidermal growth factor (EGF) and PGs were measured in patients with lung cancer treated with gefitinib, and the influence of EGF on platelet aggregation was investigated. Twenty patients were investigated. The serum level of TXB(2) increased significantly in all patients who received gefitinib for 2 weeks (before vs. after = 94.1 +/- 47.3 vs. 190.9 +/- 54.3, p<0.01). TXB(2) also increased significantly in responders without concurrent chemotherapy (before vs. after = 79.3 +/- 35.5 vs. 194.5 +/- 58.1, p<0.05), but not in non-responders (before vs. after = 106. 5 +/- 65.8 vs. 162.2 +/- 52.8, N.S.). PG 6-keto F1alpha and PGE(2) did not exhibit significant changes. Furthermore, EGF showed no significant change (after vs. before = 234 +/- 35 vs. 276 +/- 72, N.S.). Although there was no correlation between the levels of EGF and TXB(2) (N.S.), the PG 6-keto F2alpha/TXB(2) ratio decreased significantly (before vs. after = 0.054 +/- 0.018 vs 0.033 +/- 0.015, p<0.05). The secondary platelet aggregation observed after high-dose adenosine diphosphate stimulation was inhibited after a 1-minute preincubation with EGF. Platelet aggregation in patients after gefitinib administration tended to accelerate and secondary aggregation was observed after low-dose adenosine diphosphate stimulation. We conclude that careful observation is needed for patients with chronic obstructive pulmonary disease, pulmonary fibrosis, and thromboembolic diseases receiving gefitinib. Furthermore, measurement of prostanoids may be a good predictor of the beneficial and adverse effects. Moreover, the combination of gefitinib with a COX inhibitor that regulates TXA(2)/PGI(2) balance should be evaluated.

Adult↗
PubMed2005

[Consulting work performed by the hospital laboratory. Laboratory information from the screening test of blood coagulation].

Clinical laboratory physicians and scientists/technologists in the clinical laboratory of a hospital can provide much more information about laboratory data to medical doctors, by the interpretation of laboratory data, and can provide strategies to understand laboratory results. For example, in a case of circulating anticoagulant without hemorrhage, interpretation of the slightly abnormal APTT is important for precise diagnosis, although it is very difficult to interpret the data in the early stages of the disease. Recently, we experienced a patient (female, age: 61) with strong anti-phospholipid antibody and lymphoma but without thrombosis, and found spuriously elevated FDP and CRP in the patient's immunoglobulin. The information from the laboratory was invaluable in indicating the need for splenorectomy. Another case with abnormalities in blood coagulation tests was discussed. From these experiences, we confirmed that our consultations are very important and can assist in the diagnosis of patients.

Adult↗
PubMed2005

[Assessment of immunotoxicity of irinotecan determined by the novel method, by which productivity of TNF-alpha from whole blood is stimulated by lipopolysaccharide].

Irinotecan hydrochloride shows much different responses in each patient, and it has severe adverse effects. Therefore, a sensitive marker for the side effect of irinotecan on immunotoxicity may be able to prevent the severe complications by the early detection. We have recently developed a method to assess the immunotoxicity by measuring the productivity of TNF-alpha from whole blood containing monocytes when stimulated by lipopolysaccharide. By using this method, the effects of continuous low-dose irinotecan therapy on immunotoxicity were assessed in 10 patients with advanced gastric or colon cancer. When compared this method with the others such as white blood cell count, lymphocyte blastoid transformation by phytohem agglutinin (PHA), and natural killer cell activity in terms of the sensitivity, immunotoxicity by this method was found earlier than the other methods. Because our original method is easy to perform and sensitive as compared to the conventional methods, it can be widely used as one of the laboratory tests useful for patients treated with immunosuppressive agents.

Adult↗
PubMed2004

The ratio of plasma to whole-blood serotonin may be a novel marker of atherosclerotic cardiovascular disease.

Because atherosclerotic vascular lesions stimulate platelets, the platelets release serotonin (5-hydroxytryptamine, aka 5-HT). We therefore measured 5-HT concentrations not only in platelet-poor plasma but also in whole blood as a means of assessing vascular lesions. The plasma concentration of 5-HT tended to increase with age, whereas that in whole blood decreases. Therefore the ratio of the plasma to the whole-blood concentration of 5-HT (P/WB) increases with age. This may be a result of the activation of platelets in older subjects with atherosclerotic vascular damage. Patients who underwent coronary angiography (CAG) were classified into 4 groups according to diagnosis: effort-induced angina pectoris (eAP), old myocardial infarction (OMI), vasospastic angina pectoris (VSAP), and unstable angina (uAP). The mean plasma 5-HT concentration was significantly (P <.01) greater in patients with eAP, uAP, OMI, and VSAP than in healthy controls, whereas the concentration in whole blood was lower in patients with eAP than in healthy controls. When the P/WB ratios were calculated, the mean levels in all disease groups were significantly higher than that in the healthy controls. These findings suggested that 5-HT is released into the plasma from the platelets and that the concentration in the platelets decreases in patients with atherosclerosis.

Age Factors↗
PubMed2004

[Splenic marginal zone lymphoma associated with antiphospholipid antibodies].

A 61-year-old woman experienced a high fever with anemia and APTT prolongation after suffering a herpes zoster virus infection. Physical examination revealed a large splenomegaly without lymphadenopathy. Laboratory evaluations were positive for lupus anticoagulant (LA) and monoclonal IgM-kappa protein. LA was associated with the presence of anti-beta2GPI antibody, anti-cardiolipin antibody, and anti-prothrombin antibody. Moreover, the results of factors IX, XI, and XII assays and CRP and FDP-E were disturbed. A splenectomy was performed, and a splenic marginal zone lymphoma (SMZL) was diagnosed. All hematological findings rapidly recovered after the splenectomy. No thrombotic events occurred after the splenectomy even though thrombosis prophylaxis was not performed. The clinical course suggested that the SMZL-producing antibody induced immunological abnormalities in the labolatory tests. Since the patient suffered disease progression soon after the splenectomy, an autologous peripheral stem cell transplantation with rituximab administration was performed.

Antibodies, Anticardiolipin↗
PubMed2003

IL-1-induced tumor necrosis factor-alpha elicits inflammatory cell infiltration in the skin by inducing IFN-gamma-inducible protein 10 in the elicitation phase of the contact hypersensitivity response.

Contact hypersensitivity (CHS) is a typical inflammatory response against contact allergens. Inflammatory cytokines, including IL-1 and tumor necrosis factor (TNF)-alpha, are implicated in the reaction, although the precise roles of each cytokine have not been completely elucidated. In this report, we dissected the functional roles of IL-1 and TNF-alpha during CHS. CHS induced by 2,4,6-trinitorochlorobenzene as well as oxazolone was suppressed in both IL-1alpha/beta(-/-) and TNF-alpha(-/-) mice. Hapten-specific T cell activation, as examined by T cell proliferation, OX40 expression and IL-17 production, was reduced in IL-1alpha/beta(-/-) mice, but not in TNF-alpha(-/-) mice, suggesting that IL-1 but not TNF-alpha is required for hapten-specific T cell priming in the sensitization phase. On the other hand, TNF-alpha, induced by IL-1, was necessary for the induction of local inflammation during the elicitation phase. We also found that the expression of IFN-gamma-inducible protein 10 (IP-10) was augmented at the inflammatory site. Although IP-10 mRNA expression was abrogated in TNF-alpha(-/-) mice, both CHS development and TNF-alpha mRNA expression occurred normally in IFN-gamma(-/-) mice, indicating that the induction of IP-10 during CHS was primarily controlled by TNF-alpha. Interestingly, CHS was suppressed by treatment with anti-IP-10 mAb, suggesting a critical role for IP-10 in CHS. Reduced CHS in TNF-alpha(-/-) mice was reversed by IP-10 injection during the elicitation phase. Thus, it was shown that the roles for IL-1 and TNF-alpha are different, although both cytokines are crucial for the development of CHS.

Animals↗
PubMed2003

IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response.

IL-1 is a pro-inflammatory cytokine consisted of two molecular species, IL-1alpha and IL-1beta, and the IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of both molecules. Although it is suggested that IL-1 potentiates immune responses mediated by T(h)2 cells, the role of IL-1 in asthma still remains unclear. In this study, we demonstrate that the ovalbumin (OVA)-induced airway hypersensitivity response (AHR) in IL-1alpha/beta-deficient (IL-1alpha/beta(-/-)) mice was significantly reduced from the levels seen in wild-type mice, whereas the responses seen in IL-1Ra(-/-) mice were profoundly exacerbated, suggesting that IL-1 is required for T(h)2 cell activation during AHR. OVA-specific T cell proliferation, IL-4 and IL-5 production by T cells, and IgG1 and IgE production by B cells in IL-1alpha/beta(-/-) mice were markedly reduced compared with these responses in wild-type mice; such responses were enhanced in IL-1Ra(-/-) mice. Using IL-1alpha(-/-) and IL-1beta(-/-) mice, we determined that both IL-1alpha and IL-1beta are involved in this reaction. Both IgG1 and IgE levels were reduced in IL-1beta(-/-) mice, while only IgE levels were affected in IL-1alpha(-/-) mice, indicating a functional difference between IL-1alpha and IL-1beta. These observations indicate that IL-1 plays important roles in the development of AHR.

Acetylcholine↗