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Biomedical subjects

H Kodama

Publications and source records attributed to H Kodama.

At least 163 records · Page 9Linked to original sources
PubMed1998

The effects of serum iminodipeptides and prednisolone on superoxide generation and tyrosyl phosphorylation of proteins in neutrophils from a patient with prolidase deficiency.

The aim of this study was to examine the effects of serum iminodipeptides and prednisolone on superoxide generation and tyrosyl phosphorylation of proteins in neutrophils from a patient with prolidase deficiency, and also to find the causative effects of superoxide on inflammatory skin lesions. When the neutrophils from a patient with prolidase deficiency (PDPPMN) were preincubated with prolyl-proline (Pro-Pro), which is one of the iminodipeptides found at high concentration in the serum of patients with prolidase deficiency, the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation was enhanced in a concentration-dependent manner, although the extent of enhancing effect was lower than that in neutrophils from healthy humans (HPPMN). Pro-Pro also enhanced superoxide generation induced by opsonized zymosan (OZ) in PDPPMN but not that induced by arachidonic acid or phorbol 12-myristate 13-acetate. Herbimycin A and genistein decreased the fMLP- and OZ-induced superoxide generations after priming by Pro-Pro. 1-(5-isoquinoline-sulfonyl)-2-methyl-piperazine (H-7) and staurosporine did not decrease, but rather enhanced, the superoxide generation in a low concentration range. When PDPPMN were prepared, tyrosyl phosphorylation of 45 kDa protein in PDPPMN had already occurred. The phosphorylation was scarcely increased by incubation of the cells with Pro-Pro, in contrast to that in HPPMN. Genistein decreased the phosphorylation of 45 kDa protein in both PDPPMN and HPPMN. These results suggest that the priming effect of iminodipeptides on superoxide generation in PDPPMN is coupled with phosphorylation of 45 kDa protein by protein tyrosine kinase. Protein tyrosine kinase may play a critical role(s) in the regulatory mechanism of priming by iminodipeptides and activation of NADPH oxidase in the patient's neutrophils. In prolidase deficiency, the characteristic skin manifestations are inflammatory indurations and chronic leg ulcers. Prednisolone improves the ulcers, and this compound decreased the fMLP- and OZ-induced superoxide generation and tyrosyl phosphorylation of 45 kDa protein in the patient's neutrophils after priming by Pro-Pro. When inflammatory skin lesions were present, the levels of iminodipeptides in the patient's serum were elevated and the superoxide generation by neutrophils was up-regulated. When skin lesions were healing or absent, the levels of iminodipeptides in the patient's serum and superoxide generation by neutrophils were higher than those of healthy controls but lower than those in the inflammatory stages. Thus, the enhancement of superoxide generation by neutrophils via serum iminodipeptides would be one of the inducers of inflammatory skin lesions. Corticosteroid administration might be a therapeutic modality of choice for skin lesions.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Integrin beta2 (CD18)-mediated cell proliferation of HEL cells on a hematopoietic-supportive bone marrow stromal cell line, HESS-5 cells.

Cellular interactions between hematopoietic cells and stromal cells play important roles in the proliferation and differentiation of hematopoietic cells. The proliferation of a human erythroleukemia cell line, HEL cells, which can differentiate into macrophage- and megakaryocyte-like cells, and erythroid precursors was dramatically induced on coculture with a hematopoietic-supportive stromal cell line, HESS-5 cells, which can support long-term hematopoiesis in vitro without fetal bovine serum. HEL cells proliferated when they were cocultured with but not without direct cell contact. Because the coculture supernatants with direct cell contact and cytokines such as interleukins and growth factors did not exhibit growth-stimulating activity toward HEL cells, it was suggested that some molecule that has growth-stimulating activity exists on the surface of the cells. Extracellular matrix components such as fibronectin, laminin, vitronectin, and collagen did not affect the proliferation of HEL cells. An anti-CD18 monoclonal antibody, which recognizes the common beta chain of the beta2 integrin subfamily, induced dramatic proliferation of HEL cells. Moreover, the proliferation of HEL cells was inhibited by an antisense oligonucleotide of CD18 mRNA. As judged from these observations, the proliferation of HEL cells was mediated by CD18 molecules expressed on HEL cells. On the contrary, the common counter-receptor of the beta2 integrin subfamily, intercellular adhesion molecule-1, which is expressed on CHO-K1 cells, did not stimulate the growth of HEL cells. It is known that other counter molecules of the beta2 integrin subfamily, such as complement C3bi and fibrinogen, are not produced by stromal cells. These findings suggest that the proliferation of HEL cells may be induced through an interaction between a novel molecule of the beta2 integrin subfamily on HEL cells and the counter-receptor on HESS-5 cells. The beta2 integrin subfamily may regulate the growth of hematopoietic cells in hematopoiesis in vivo and/or cause the abnormal growth of leukemia cells.

Animals↗
PubMed1998

Biphasic activation of the JAK/STAT pathway by angiotensin II in rat cardiomyocytes.

This study was designed to demonstrate the characteristic pattern of angiotensin II-induced JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) activation in cultured rat cardiomyocytes by comparing it with leukemia inhibitory factor (LIF)-induced activation. Angiotensin II (10(-7) mol/L) induced rapid phosphorylation of JAK2 and Tyk2, but not JAK1, and phosphorylated STAT1 and STAT2, but not STAT3, in the early stage up to 30 minutes. The time course of JAK/STAT activation by angiotensin II was apparently slower than that by LIF. Interestingly, angiotensin II phosphorylated STAT3 and rephosphorylated STAT1 in the late stage at 120 minutes. We also found that angiotensin II induced the formation of interferon-stimulating gene factor (ISGF) complexes biphasically, in the early stage at 15 to 30 minutes and in the late stage at 120 minutes, and that angiotensin II induced delayed activation of the sis-inducing factor (SIF) complex at 120 minutes. Formation of ISGF and SIF complexes in response to angiotensin II paralleled the phosphorylation pattern of STAT1 and STAT3 and was quite different from those obtained in response to LIF. The phosphorylation of STAT1 was suppressed by pretreatment with the angiotensin II type-1 (AT1) receptor antagonist CV11974, but the delayed addition of CV11974 failed to suppress phosphorylation of STAT3 at 120 minutes. In conclusion, angiotensin II-induced JAK/STAT activation in rat cardiomyocytes is biphasic and entirely different from LIF-induced activation.

Angiotensin II↗
PubMed1998

Stimulation of G-CSF gene expression in the macrophage cell line by contact with extracellular matrix proteins and a pre-B leukaemia cell line.

In order to scrutinize the adherence-dependent interactions for induction of granulocyte colony-stimulating factor (G-CSF) in peripheral monocytes/macrophages, a sensitive reporter gene assay was constructed using the mouse macrophage cell line transfected with the mouse G-CSF promoter region in conjunction with the luciferase gene as a reporter. With this system, lipopolysaccharide (LPS) showed a markedly positive response. Among the extracellular matrix (ECM) proteins, both fibronectin (FN) and vitronectin (VN) markedly induced luciferase activity, but others did so but much lesser extent. Among the synthetic peptides having Arg-Gly-Asp (RGD) sequences, only FLEPP with multiple RGD significantly induced luciferase activity. Pretreatment of the cells with anti-integrin alpha 6, alpha M, beta 1 and beta 2 monoclonal antibodies (mAbs) significantly reduced the LPS-induced responses and anti-alpha 1, alpha 2 and beta 3 mAbs to lesser extent, and anti-alpha 5, alpha 6, alpha M, beta 1 and beta 2 mAbs blocked the FN-induced response. In the cell-to-cell interactions, significantly positive increase was observed by direct contacting this cell line with a G-CSF-dependent promyelocytic leukaemia cell line, known to stimulate the induction of G-CSF to the stromal cells. Its effect was mostly blocked by pretreatment with anti-integrin alpha 5, alpha L, beta 1 and beta 2 and anti-ICAM-1 mAbs. These results indicate that there are several pathways via the cell-to-ECM and cell-to-cell interactions triggering the induction of G-CSF in the macrophages.

Animals↗
PubMed1998

Hypotaurine disproportionation reaction: identification of products.

Hypotaurine, concentrated under reduced pressure in HCl solution, partially (30-40%) degrades into taurine (about 30%), 2-aminoethyl-2-aminoethanethiolsulfonate (about 10%) and ethanolamine. The degradation products were identified using LC/APCI-MS, NMR, amino acid analysis and various chromatographies. The identities were confirmed by comparing the HPLS, MS and NMR characteristics of authentic compounds. One of the degradation processes during concentration of HCl solution of hypotaurine is therefore a disproportionation reaction which can interfere with the experimental results, when studying hypotaurine in biological systems.

Chromatography, High Pressure Liquid↗
PubMed1998

Involvement of gp130-mediated signaling in pressure overload-induced activation of the JAK/STAT pathway in rodent heart.

Previously, we showed that the JAK/STAT pathway was activated in pressure-overloaded rat heart, and that angiotensin II was partially involved in this activation. The present study was designed to investigate whether gp130-mediated signaling is involved in this activation, and if so, which interleukin (IL)-6 family cytokine is involved. Pressure overload was produced by ligation of the abdominal aorta of Wistar rats or ICR mice. IP-Western blot was performed to detect tyrosine phosphorylation of STATs, gp130, and the association of gp130 with JAK kinases. The serum concentration of IL-6 was measured by enzyme-linked immunosorbent assay. Expression of IL-6, IL-11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), and cardiotrophin-1 (CT-1) mRNA was quantitated. After pressure overload, rapid phosphorylation of STAT1 and STAT3 was observed at 5 min, STAT1 was rephosphorylated at 60 min, and intense phosphorylation of STAT3 was observed at 60 min. Both the phosphorylation of gp130 and the association of gp130 with JAK1 and JAK2 were increased after pressure overload. IL-6 was significantly increased by two-fold in the pressure-overloaded rats. Only CT-1 mRNA expression could be detected by Northern blot, and it increased after pressure overload. Reverse transcription-polymerase chain reaction revealed that IL-6 mRNA expression was increased 9.5-fold. IL-11, LIF, CNTF, and OSM expression were unaffected by pressure overload. These results suggested that gp130-mediated signaling was involved in the pressure overload-induced activation of the JAK/STAT pathway, and that IL-6 and CT-1 might be involved in this activation.

Animals↗
PubMed1998

Seroma with fibrous capsule formation requiring a surgical resection after a modified radical mastectomy: report of a case.

Seroma formation is the most common complication of a modified radical mastectomy for breast cancer. Although various management or risk factors for seroma formation have been previously reported, little has been published concerning seromas with fibrous capsule formation which ultimately require a surgical resection. We herein present a case who developed a seroma with a fibrous capsule after a modified radical mastectomy for breast cancer, in spite of an uneventful intraoperative and postoperative course. The seroma was refractory to all conventional treatments, and thus finally required a surgical resection.

Axilla↗
PubMed1998

The role of cytokines in cervical ripening: correlations between the concentrations of cytokines and hyaluronic acid in cervical mucus and the induction of hyaluronic acid production by inflammatory cytokines by human cervical fibroblasts.

OBJECTIVES: The purpose of our study was (1) to explain the relationship between levels of inflammatory cytokines and levels of hyaluronic acid in cervical mucus of pregnant women and (2) to investigate whether cytokines promote hyaluronic acid production by human cervical fibroblasts in vitro. STUDY DESIGN: The concentration of hyaluronic acid, interleukin-1beta, and interleukin-8 were measured in cervical mucus of pregnant women, and hyaluronic acid production by cytokine-treated (interleukin-1beta and interleukin-8) cultured fibroblasts was measured. RESULTS: Hyaluronic acid concentrations in the mucus of pregnant women with threatened premature labor were higher than in mucus of normal pregnant women (P < .05). Correlations were found between hyaluronic acid concentrations and interleukin-1beta (P = .018) and interleukin-8 (P = .003) concentrations in cervical mucus. Cytokines (especially interleukin-8) stimulated hyaluronic acid production by cultured cervical fibroblasts. CONCLUSION: Cytokines induce hyaluronic acid production by human cervical fibroblasts, which may promote cervical ripening.

Adult↗
PubMed1998

Metabolism of cystathionine, N-monoacetylcystathionine, perhydro-1,4-thiazepine-3,5-dicarboxylic acid, and cystathionine ketimine in the liver and kidney of D,L-propargylglycine-treated rats.

Experimental cystathioninuria was induced by injection of D,L-propargylglycine in rats. The novel cystathionine metabolites, N-monoacetylcystathionine (NAc-cysta), perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), and cystathionine ketimine (CK), were identified previously in the urine of patients with cystathioninuria and D,L-propargylglycine-treated rats. In this study, we identified these compounds in the liver and kidney of D,L-propargylglycine-treated rats using liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system (LC/APCI-MS) and an amino acid analyzer. The metabolism of these compounds in the liver and kidney of D,L-propargylglycine-treated rats was also studied. PHTZDC, NAc-cysta, and CK were accumulated in the rat tissues in proportion to the content of cystathionine after D,L-propargylglycine administration. The concentrations of these compounds in the liver were higher than those in the kidney, and these compounds reached maxima earlier in the liver than in the kidney.

Alkynes↗
PubMed1998

Expression of extensin genes is dependent on the stage of the cell cycle and cell proliferation in suspension-cultured Catharanthus roseus cells.

To isolate cDNAs expressed at a specific phase of the cell cycle in a higher plant, we performed differential screening of a cDNA library prepared from the S-phase cells of synchronized cultures of Catharanthus roseus. Sequence analysis shows that two of the identified cDNAs, cyc15 and cyc17, encode extensins that represent a family of cell wall hydroxyproline-rich glycoproteins. Protein sequences deduced from the two cDNAs contain the characteristic pentapeptide repeat sequence, Ser-Pro-Pro-Pro-Pro, which is commonly observed in extensins. The protein sequences also share several other extensin characteristics such as the presence of a N-terminal signal peptide and a high content of Tyr and Lys residues. When C. roseus cell suspension cultures were synchronized by phosphate starvation, the mRNAs of both cyc15 and cyc17 were transiently expressed during the S and G2 phases of the cell cycle. However, significant amounts of the mRNAs also accumulated in phosphate-starved cells arrested in the G1 phase. In asynchronous cultures, both genes were expressed during the stationary phase, when cell proliferation ceased. The observed patterns of expression suggest that the extensin genes, cyc15 and cyc17, are under two types of regulation: one that depends on the stage of the cell cycle and another that is induced during the growth arrest. Thus, the products of these genes may function both during the progression through the cell cycle and in the strengthening of the cell wall after cell division.

Amino Acid Sequence↗
PubMed1998

Two maize genes encoding omega-3 fatty acid desaturase and their differential expression to temperature.

We have isolated two maize cDNAs and the corresponding genes encoding fatty acid desaturase with Arabidopsis thaliana FAD7 gene as a probe. They shared almost 90% identity at DNA sequence level. Northern analysis revealed that both genes are expressed in leaves, but not in roots at normal temperature- and low temperature-growth condition. The overall level of these transcripts are elevated upon exposure to low temperature. The tissue-specific expression and DNA sequence data indicate that both genes encode plastidic omega-3 fatty acid desaturases. One of them is expressed exclusively at normal temperature but not at 5 degrees C, whereas the other is expressed inversely. We, therefore, termed them ZmFAD7 and ZmFAD8, respectively. Among other stresses, high-salt treatment induced the accumulation of the ZmFAD7 and ZmFAD8 transcripts in roots but drought had no effect on their expression. Cycloheximide induced the accumulation of the ZmFAD7 transcript in roots. The genomic clones of ZmFAD7 and ZmFAD8 consist of 8 exons and 7 introns as same as in the cases of A. thaliana FAD7 and FAD8 genes and the sizes of the 6 internal exons were identical among them. A phylogenetic analysis of ZmFAD7, ZmFAD8 amino acid sequences and those originated from other plant species is also presented.

Amino Acid Sequence↗
PubMed1998

Serum protein binding kinetics of phenytoin in monotherapy patients.

OBJECTIVES: To determine the binding characteristics of phenytoin to serum proteins in the Japanese population and to compare these with those reported by other investigators. METHOD: Serum samples examined in the study were obtained from 72 patients (35 males, 37 females) receiving phenytoin monotherapy. The patients' ages ranged from 1 to 73 years (1-15 years, 36 subjects; 16-44 years, 20 subjects; 45-64 years, 13 subjects; > or = 65 years, 3 subjects). RESULTS: The in vivo population binding parameters of phenytoin to serum proteins and theoretical minimal unbound serum phenytoin fraction (fu) were determined using the Scatchard equation. The association constant (K) was 0.020 1/micromol, while the total concentration of binding sites (n(Pt) was 556 micromol/l. The number of binding sites per albumin molecule (n) was 0.85, while binding ability (n.K) was 0.017 l/micromol. The fu was 0.083. The n.K is approximately 1.1 times higher in patients of Pospísil et al. (26) (i.e. 0.0191 l/micromol) than in all our patients. The association constant is approximately 1.1 times higher in our study than in the in vitro study of Monks et al. (23) (i.e. 0-0186 l/micromol), while n is similar between the two studies. The fu in our patients is similar to the unbound serum phenytoin fraction in adult patients receiving phenytoin therapy reported by Richens (2) (i.e. 0.1). CONCLUSION: Our results suggest that there may be small differences in the binding characteristics of phenytoin to serum proteins between Japanese and non-Japanese subjects. The unbound serum fraction of phenytoin in our patients with epilepsy can be assumed to be relatively constant in the therapeutic concentration range of phenytoin.

Adolescent↗
PubMed1998

Serum antibodies specific to CD outer membrane protein of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae and capsular polysaccharides of Streptococcus pneumoniae in children with otitis media with effusion.

We measured the levels of serum IgG antibodies to CD outer membrane protein of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae and capsular polysaccharides of Streptococcus pneumoniae in 168 children with otitis media with effusion (OME) who were followed prospectively, using ELISA. Serum IgG antibodies to CD, P6 and pneumococcal capsular polysaccharides were detected in all samples. The anti-pneumococcal polysaccharides antibody level was highest, followed by the anti-P6 antibody level and anti-CD antibody was lowest (median:interquartile ranges were 45.9:19.1-100 microg/ml, 15.6:9.70-23.2 microg/ml and 1.06:0.73-1.87 microg/ml, respectively). In children aged 0-6 years, there were positive correlations among the antibody levels (anti-CD vs anti-P6, r=0.325, p <0.001; anti-CD vs anti-polysaccharide, r=0.397, p <0.0001; anti-P6 vs anti-polysaccharide, r=0.175, p=0.057). However, no relationship was seen in children aged 7-15 years. Children were classified according to severity of OME during the 1-year follow-up. In children aged 0-6 years, the severity of OME correlated inversely with the levels of anti-CD antibody (r=-.23, p=0.012), of anti-P6 antibody (r=-0.292, p=0.0015), and of anti-pneumococcal polysaccharides antibody (r=-0.25, p=0.0064). However, no correlation was found between antibody levels and severity of OME in children aged 7-15 years. These data suggest that persistence and/or recurrence of OME may be due to an insufficient serum antibody response to middle ear pathogens in young children.

Adolescent↗
PubMed1998

Possible involvement of very low density lipoproteins in steroidogenesis in the human ovary.

To determine whether human luteal cells can utilize very low density lipoproteins (VLDL)-carried cholesterol for steroidogenesis, we investigated the expression of VLDL receptor mRNA in human ovarian tissues and progesterone production by human luteinized granulosa cells after the addition of VLDL. The production of progesterone in the presence of human chorionic gonadotrophin (HCG) was increased significantly (P < 0.05) by VLDL (2479 +/- 1477 ng/10(5) cells, mean +/- SD, n = 6) and low density lipoproteins (LDL) (2726 +/- 1287), in comparison with the level in the absence of these lipoproteins (1350 +/- 739). Northern blot analysis revealed that the levels of expression of VLDL and LDL receptor mRNA in granulosa cells were almost equal to those in whole ovarian tissue. VLDL receptor mRNA was abundant in granulosa cells of preovulatory follicles and cells of the corpus luteum. Preovulatory thecal cells and stromal cells expressed lower amounts of VLDL receptor mRNA than granulosa cells of preovulatory follicles and cells of the corpus luteum. From the present study, it might be suggested that VLDL is utilized for steroidogenesis in human luteinized granulosa cells.

Blotting, Northern↗