PubMed Health⌕ Search

Biomedical subjects

K Imagawa

Publications and source records attributed to K Imagawa.

At least 19 recordsLinked to original sources
PubMed1999

An assessment of the immunological environment based on intratumoral cytokine production in renal cell carcinoma.

OBJECTIVE: To assess the immunological relationship between tumour and host, focusing on the production of T-cell helper (Th) subset-derived cytokines in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 35 patients (19 men and 16 women, mean age 56.9 years, range 39-78) with RCC, who had undergone nephrectomy. Using enzyme-linked immunosorbent assays, the levels of Th1-derived cytokines were measured, including interleukin (IL)-2 and interferon (IFN)-gamma, and Th2-derived cytokines, including IL-4, IL-5, IL-6, IL-10 and others. RESULTS: There was no detectable IL-2 or IFN-gamma production (below the detection limit) except in two patients; IL-4 was produced in 18 patients (51%) and of these, 15 (43%) showed a higher level than the mean. IL-5 was produced in 12 patients (34%), all of whom showed a higher level than the mean, and IL-6 was produced in 32 (91%) of whom 10 (29%) showed a higher level than the mean. IL-10 was detected in 28 patients (80%) of whom 14 (40%) showed a higher level than the mean. The production of these cytokines was closely related to the stage and grade of malignancy. Furthermore, there were significant correlations between the levels of production of IL-4 and IL-5 (r2=0.92), IL-4 and IL-10 (r2=0.91), and IL-5 and IL-10 (r2=0.85). CONCLUSION: The intratumoral immunological environment in patients with RCC shows a tendency to produce Th2-related cytokines in accordance with the stage and grade; this suggests a role in humoral but not in cellular immunity.

Adult↗
PubMed1999

Analysis of where and which types of proteinases participate in lysosomal proteinase processing using bafilomycin A1 and Helicobacter pylori Vac A toxin.

Lysosomal proteinases are translated as preproforms, transported through the Golgi apparatus as proforms, and localized in lysosomes as mature forms. In this study, we analyzed which subclass of proteinases participates in the processing of lysosomal proteinases using Bafilomycin A1, a vacuolar ATPase inhibitor. Bafilomycin A1 raises lysosomal pH resulting in the degradation of lysosomal proteinases such as cathepsins B, D, and L. Twenty-four hours after the withdrawal of Bafilomycin A1, NIH3T3 cells possess these proteinases in amounts and activities similar to those in cells cultured in DMEM and 5% BCS. In the presence of various proteinase inhibitors, procathepsin processing is disturbed by E-64-d, resulting in abnormal processing of cathepsins D and L, but not by APMSF, Pepstatin A, or CA-074. In the presence of Helicobacter pylori Vac A toxin, which prevents vesicular transport from late endosomes to lysosomes, the processing of procathepsins B and D occurs, while that of procathepsin L does not. Thus, procathepsins B and D are converted to their mature forms in late endosomes, while procathepsin L is processed to the mature form after its arrival in lysosomes by some cysteine proteinase other than cathepsin B.

3T3 Cells↗
PubMed1998

Structure-function studies of human leptin.

To elucidate the structural requirement of human leptin for its functions, the wild-type, mutant-type, C-terminal deletion, and N-terminal deletion were expressed in Escherichia coli and purified in soluble forms. These leptin analogs were intracerebroventrically injected into C57BL/6J ob/ob mice, and their in vivo biological activities were evaluated. The mutant-type leptin lacking a C-terminal disulfide bond reduced food intake at doses of more than 15 pmol/mouse, which was as effective as the wild-type leptin. C-terminal deletion without the loop structure, also significantly, but to a lesser extent, reduced food intake at doses of more than 90 pmol/mouse. However, N-terminal deletions showed no effect on food intake. We also evaluated the effects of the leptin analogs on radiolabeled leptin binding to its receptor in the choroid plexus using autoradiography. An excess of unlabeled mutant-type leptin as well as wild-type leptin led to complete inhibition of binding. C-terminal deletions led to weak inhibitory activity, whereas N-terminal deletions caused no inhibitory activity. These results clearly demonstrate that the N-terminal region of leptin is essential for both its biological and receptor binding activities. The amino acid sequence of the C-terminal loop structure is also important for enhancing these actions, whereas the C-terminal disulfide bond is not needed.

Animals↗
PubMed1998

Delayed gastric emptying by Helicobacter pylori lipopolysaccharide in conscious rats.

The present study was carried out to investigate the possibility that lipopolysaccharide deprived from Helicobacter pylori may alter gastric motility. To address the question, we examined the effect of H. pylori lipopolysaccharide on gastric emptying in conscious rats. Gastric emptying was evaluated by the phenol red method. Time-course and dose-related effects of intraperitoneal administration of H. pylori lipopolysaccharide were investigated. Intraperitoneal injection of H. pylori lipopolysaccharide significantly suppressed gastric emptying of a liquid meal in a dose-dependent manner. The inhibitory action of H. pylori lipopolysaccharide was observed 2, 4, 8, or 12 hr after the injection. These results suggest for the first time that H. pylori lipopolysaccharide may suppress gastric emptying in a long-lasting fashion. It is also suggested that H. pylori may influence gastric function through its cell wall structure named lipopolysaccharide.

Animals↗
PubMed1998

[Study on the relationship between tumour necrosis factor gene polymorphism and prognosis in the patients with renal cell carcinoma].

BACKGROUND: Clinical significance of polymorphism of tumour necrosis factor (TNF) genes encoded on the short arm of the 6th chromosome in the patients with renal cell carcinoma (RCC) has not been evaluated well so far. We studied on the TNF genes polymorphism of RCC focusing on the relationship between the genetic polymorphism and the prognosis. METHODS: The subjects were seventy-three patients with RCC treated at our hospitals during the past 20 years. The genomic DNA was examined by the methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) from frozen peripheral blood of these patients. The items examined were the genetic polymorphisms of TNF-alpha (alpha 1, alpha 2) and TNF-beta (beta 1, beta 2), and we tried to study on the prognostic outcome of RCC based upon each zygote of TNF. RESULTS: 1) The proportion of TNF-alpha and TNF-beta polymorphisms: We observed TNF-alpha 1/1 homozygote in 71 patients (97.3%). As to TNF-beta polymorphism, we observed TNF-beta 2/2 homozygote in 33 patients (45.2%), TNF-beta 1/2 heterozygote in 31 (42.5%) and TNF-beta 1/1 homozygote in 9 (12.3%). The proportion of TNF-beta polymorphism was almost the same as that of healthy Japanese. 2) PROGNOSIS: Regarding the 17-year survival, all patients with TNF-beta 1/1 homozygote were alive, and we observed a significantly favourable prognosis in the patients with TNF-beta 1/1 homozygote compared with other zygotes of TNF-beta polymorphism. The reasons for these favourable prognosis were thought that the patients with TNF-beta 1/1 homozygote showed much lower stage and/or grade than those of other zygotes. CONCLUSION: We conclude that the TNF-beta gene polymorphism is a useful marker for understanding the prognosis of RCC and a part of cellular immunity related to the tumour and its host.

Adult↗
PubMed1998

[Study on the combined therapy of DNA-methyltransferase inhibitor and interferon-alpha/beta for mouse spontaneously arose renal cell carcinoma, and immunological mechanism induced by the therapy].

BACKGROUND: In order to change the immunological environment of T-helper2 (Th2) predominance, namely humoural immunity, in renal cell carcinoma, we tried to examine the efficacy of combined treatment with DNA-methyltransferase inhibitor (Procainamide) and interferon (IFN)-alpha/beta in basic experiments, and also examined the immunological mechanism induced by this treatment modality. MATERIALS AND METHODS: The monotherapy of Procainamide (10 mg/kg, 20 mg/kg, 30 mg/kg, everyday for 3 weeks, i.p.) and of natural murine IFN-alpha/beta (1 x 10(4) I.U./mouse, 3 times for a week, total 9 times, s.c.), and combined treatment with these 2 drugs for mouse spontaneously arose renal cell carcinoma (RC-2) were undertaken. Furthermore, we examined the expression of cytokine mRNA related to the Th-subset in murine spleen under the tumour burden by the RT-PCR methods. RESULTS: 1) Regarding the anti-tumour efficacy of two kinds of monotherapy (Procainamide and IFN-alpha/beta), no effective result was obtained. On the other hand, the combined treatment with these two drugs induced effective anti-tumour efficacy in the relative mean tumour weight ratio (TRW/CRW), mean tumour weight and the survival rate compared with the control and each monotherapy, especially in the administration of Procainamide dosed at 30 mg/kg. As to the histological degeneration induced by the combined therapy, there still remained the viable tumour cells (grade IIb). 2) In an effort to analyse the immunological changes induced by the administration of Procainamide, there observed the expression of Th1-derived cytokines mRNA such as IFN-gamma, IL-2 and tumour necrosis factor-beta, and except for interleukin (IL)-10, there also observed the disappearance of Th2-derived cytokines mRNA such as IL-4, IL-5 and IL-6 in the murine spleen. CONCLUSION: We draw the conclusion that the treatment with DNA-methyltransferase inhibitor may change the humoural immunological environment into the cellular immunological environment enabling the effective anti-tumour efficacy combined with IFN-alpha/beta in renal cell carcinoma.

Animals↗
PubMed1998

IFN-gamma-induced iNOS mRNA expression is inhibited by rebamipide in murine macrophage RAW264.7 cells.

To investigate the effects of rebamipide, an antigastritis and anti-gastric ulcer drug, on inducible nitric oxide synthase (iNOS), murine macrophage RAW264.7 cells were treated with interferon-gamma (IFN-gamma) in the presence of rebamipide. NO production was stimulated by IFN-gamma, and the level was attenuated by rebamipide in a dose-dependent manner. Therefore, we investigated the possibility that either rebamipide directly inhibited iNOS enzyme activity or that it reduced iNOS mRNA expression. In a cell-free system, rebamipide did not affect iNOS enzyme activity; however, rebamipide inhibited iNOS mRNA and protein expression induced by IFN-gamma. Thus, we concluded that rebamipide inhibited IFN-gamma-induced NO production as a result of its inhibitory action on iNOS mRNA expression.

Alanine↗
PubMed1998

Effects of rebamipide on production of several cytokines by human peripheral blood mononuclear cells.

Recently, the relative contributions of local T helper cell responses of the Th1-type and Th2-type to the pathogenesis of gastritis and peptic ulcers associated with Helicobacter pylori infection have been examined. However, the results were controversial with respect to whether cellular immunity (Th1-type) or humoral immunity (Th2-type) responses predominate in H. pylori infection and with respect to how these responses may contribute to disease pathogenesis. In this study, we investigated the characteristics of the production of various cytokines induced by H. pylori or lipopolysaccharide (LPS), which was derived from H. pylori or Escherichia coli, in human peripheral blood mononuclear cells (PBMC). Live H. pylori induced production of many cytokines, such as IL-1beta, IL-10, IL-8, IFN-gamma, and TNF-alpha, whereas we could not detect IL-2 or IL-4. Moreover, we evaluated the effect of rebamipide on the production of several cytokines from PBMC induced by various stimuli. Rebamipide suppressed the production of IL-8, IL-10, TNF-alpha, and IL-1beta induced by H. pylori in a dose-dependent manner. On the other hand, the production of IL-12 induced by H. pylori showed a tendency to increase as a result of treatment of the cells with rebamipide. These results suggested that rebamipide might be effective in regulating cytokine responses in the H. pylori-infected host and maintaining host immunity. Moreover, it might contribute positively to disease progression and bacterial eradication.

Alanine↗
PubMed1998

Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines.

Interleukin-8 (IL-8) may play an important role in Helicobacter pylori infection-associated chronic active gastritis and peptic ulcer disease in human. We have recently reported that a gastric cancer cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori. Moreover, H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription. In this study, we evaluated the effect of rebamipide, an antigastritis and antiulcer agent, on H. pylori-induced IL-8 production. Rebamipide inhibited the production of IL-8 in several gastric cancer cell lines infected with H. pylori. In addition, rebamipide suppressed H. pylori-induced IL-8 gene expression at the transcriptional level as revealed by northern blotting analysis and luciferase activity in cells that were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44). Furthermore, rebamipide significantly suppressed the NF-kappaB activation by H. pylori infection. These results suggest that rebamipide may protect against the mucosal inflammation associated with H. pylori infection through inhibition of a proinflammatory cytokine, IL-8.

Alanine↗
PubMed1998

Development of a sensitive ELISA for human leptin, using monoclonal antibodies.

A new, sensitive ELISA for human leptin in plasma and cerebrospinal fluid (CSF) was developed, using monoclonal antibodies. The lower limit of detection of this ELISA was 0.78 pg/assay. Both intra- and interassay imprecision values were <7%. The dilution curves of plasma and CSF showed good linearity, and the recovery was 83.2-95.6%. There was good correlation between plasma leptin concentrations by the ELISA and a commercially available RIA (r = 0.99). Our ELISA is advantageous because it does not require radioisotopes, it produces results in hours rather than days, and more importantly, it improves on the detection limit and plasma interference of the RIA kit. The new ELISA enables measurement of low concentrations of leptin, as are seen in CSF and in plasma of patients with anorexia nervosa.

Adipose Tissue↗
PubMed1997

Helicobacter pylori lipopolysaccharide inhibits acid secretion in pylorus-ligated conscious rats.

To examine the effect of Helicobacter pylori lipopolysaccharide on gastric secretion, the present study was carried out using pylorus ligated conscious rats. Intraperitoneal administration of Helicobacter pylori lipopolysaccharide significantly inhibited gastric acid secretion (4 hr) in a dose-dependent manner (0.033-1.0 mg/rat). The Helicobacter pylori lipopolysaccharide (1 mg/rat)-induced acid inhibition was still observed 8 hr after injection. Gastric acid secretion (4 hr) was compared in the rats that had received intraperitoneal administration of 1 mg/rat dose of Helicobacter pylori lipopolysaccharide or saline alone 24 hr before. There was no significant difference in gastric acid secretion between the saline- and H. pylori lipopolysaccharide-treated rats. These results suggest for the first time that H. pylori lipopolysaccharide may inhibit acid production, and this acid inhibition may be long-lasting. It is also demonstrated that this anti-secretory action of H. pylori lipopolysaccharide has a reversible effect on gastric secretion. All these results suggest that H. pylori lipopolysaccharide might be involved in the low acid secretory function seen in patients with acute H. pylori infection.

Animals↗
PubMed1997

The arcuate nucleus as a primary site of satiety effect of leptin in rats.

The obese (ob) gene encodes a fat cell-derived circulating satiety factor (leptin) that is involved in the regulation of energy homeostasis. In the present study, we examined effects of i.c.v. injection of recombinant human leptin on food intake and body weight gain in rats. We also studied effects of direct microinjections of leptin into the arcuate nucleus (Arc), ventromedial hypothalamus (VMH), and lateral hypothalamus (LH). A single i.c.v. injection of recombinant human leptin (0.25-2.0 micrograms/rat) reduced significantly and dose-dependently food intake and body weight gain in rats. Microinjections (0.125-0.5 microgram/site) into the bilateral Arc, VMH, and LH caused dose-related decreases in food intake and body weight gain as compared with vehicle-treated groups with a rank order of potency; Arc > VMH = LH. The present study provides the first direct evidence that the Arc is a primary site of satiety effect of leptin.

Animals↗
PubMed1997

Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45.

Accumulating evidence suggests an important role of interleukin-8 (IL-8) in Helicobacter pylori infection-associated chronic atrophic gastritis and peptic ulcer. We observed in this study that a gastric cancer-derived cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori but not with killed H. pylori, H. pylori culture supernatants, or live H. pylori separated by a permeable membrane, indicating that IL-8 production requires a direct contact between the cells and live bacteria. Moreover, the tyrosine kinase inhibitor herbimycin but neither a protein kinase C inhibitor (staurosporine) nor a protein kinase A inhibitor (H89) inhibited IL-8 production by MKN45 cells cocultured with live bacteria, suggesting the involvement of a tyrosine kinase(s) in H. pylori-induced IL-8 production. In addition, coculture of H. pylori induced IL-8 mRNA expression in MKN45 cells and an increase in luciferase activity in cells which were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44), indicating that the induction of IL-8 production occurred at the transcriptional level. This region contain three cis elements important for induction of IL-8 gene expression: AP-1 (-126 to -120 bp), NF-IL6 (-94 to -81 bp), and NF-kappaB (-80 to -70 bp) binding sites. Mutation of the NF-kappaB binding site abrogated completely the induction of luciferase activity, whereas that of the AP-1 site partially reduced the induction. However, mutation of the NF-IL6 binding site resulted in no decrease in the induction of luciferase activity. Moreover, specific NF-kappaB complexes were detected in the nuclear proteins extracted from MKN45 cells which were infected with H. pylori. Collectively, these results suggest that H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription.

Gene Expression Regulation↗
PubMed1996

Phenotype frequency of human leukocyte antigens in Japanese patients with renal cell carcinoma who responded to interferon-alpha treatment.

BACKGROUND: Because of the high cost, low overall response rate (10% to 20%), and poor quality of life during interferon therapy for advanced renal cell carcinoma, it is important to distinguish patients likely to respond to treatment. The expression of human leukocyte antigens (HLA) may serve as a clinical marker for response to interferon treatment in patients with renal cell carcinoma. METHODS: We compared HLA phenotype frequency in 37 Japanese patients with advanced renal cell carcinoma who showed a favorable response to interferon-alpha, in 93 similar patients, before treatment, who did not receive interferon-alpha, and in 939 healthy Japanese volunteers (historical control data). RESULTS: Six HLA antigens, B35, Bw48, Bw60, DRw6, DRw8, and DR9, were expressed at a significantly lower rate in the 93 pretreatment patients with renal cell carcinoma, compared with the control subjects. Three HLA antigens, excluding Bw60, DRw6, and DRw8, were expressed at a significantly higher rate in the patients who responded to interferon-alpha, compared with the pretreatment patients with renal cell carcinoma and control subjects. CONCLUSION: Three HLA antigens, B35, Bw48, and DR9, were expressed at a significantly higher rate in patients with renal cell carcinoma who showed a sensitivity to interferon-alpha, and could be important markers for clinical response to this antitumor therapy.

Adult↗
PubMed1995

Cervical flexion myelopathy associated with cervical spina bifida occulta--case report.

A 16-year-old boy presented with segmental muscular atrophy of the bilateral distal upper extremities. Cervical spine x-ray films showed occult spina bifida from C-1 to T-1 associated with an abnormal long club-like bone located parallel to the epidural space between C-5 and C-7. In neck flexion, the cervical spinal cord was stretched and compressed to the posterior aspect of the vertebral body. Moreover, the dorsally placed abnormal bone migrated ventrally, indenting the dorsal portion of the spinal cord. This is quite an unusual case of so-called "flexion myelopathy," aggravated by the abnormal bone located dorsally.

Adolescent↗
PubMed1995

[MRI of traumatic anosmia].

On MRI, the authors were able to demonstrate the contused lesions of bilateral rectal gyri near the crista galli in all of five cases of traumatic anosmia. Thin slice coronal and sagittal images of MRI were very useful for detecting the lesions. Conventional CT scans failed to demonstrate the lesions in 3 out of the 5 cases, but, even in these cases, MRI was able to clearly depict the contused lesions of bilateral rectal gyri. Therefore, the depicted lesions of bilateral rectal gyri on MRI can be evidence of traumatic anosmia and this may be very significant in medico-legal cases.

Adolescent↗
PubMed1994

Dural sinus thrombosis in Behçet's disease--a case report.

Sinus thrombosis, which causes pseudotumor cerebri, is difficult to diagnose with conventional imaging apparatus, CT and MRI. We report a case of sinus thrombosis due to Behçet's disease diagnosed by magnetic resonance angiography (MRA). A forty-five-year old man with severe headache and ocular pain was examined. Since he had a history of oral ulcers, genital ulcers, and erythema nodosum venous thrombosis, he had been diagnosed as having Behçet's disease previously. He showed marked papilledema bilaterally but no obvious intracranial lesion was observed by CT and MRI. On MRA, an obstruction was apparent at the sagittal sinus. Anticoagulant and steroid therapy were effective to relieve the headache, and to improve the constricted visual field temporarily. By MRA, blood flow was confirmed in the sagittal sinus. However, mild papilledema persisted and finally vision was lost because of optic atrophy.

Behcet Syndrome↗