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H Kondo

Publications and source records attributed to H Kondo.

At least 73 records · Page 4Linked to original sources
PubMed2001

Senescence and cytoskeleton: overproduction of vimentin induces senescent-like morphology in human fibroblasts.

One characteristic feature of senescent fibroblasts is flat, enlarged, and heterogeneous cell shapes. The present study was aimed to understand the structural basis of the senescent cell morphology. SDS-gel electrophoresis as well as western blotting demonstrated that there occurred a prominent protein band about 57 kDa in the senescent cells as compared with normal young or immortalized cells growing rapidly, and the protein was identified with a cytoskeletal protein, vimentin. In fact, senescent fibroblasts contained approximately threefold more vimentin protein, and fourfold more vimentin mRNA than young embryonic fibroblasts. In the senescent cells, vimentin cytoskeleton occurred as densely bundled filaments in parallel with the long axis of cell bodies, whereas in young or actively growing cells it showed short and thin vimentin filaments or fur-like irregular networks. It was further demonstrated that senescent cell shapes could be induced when a vimentin expression construct was transfected in young fibroblasts. These results suggest that senescent fibroblasts overproduce vimentin protein, and the overproduced vimentin filaments bring about the senescent cell morphology.

Adult↗
PubMed2001

Delineation of the critical interval for the familial exudative vitreoretinopathy gene by linkage and haplotype analysis.

Familial exudative vitreoretinopathy (FEVR) is an ocular disorder characterized by deficient vascularization of the peripheral retina and causes visual loss attributable to various types of retinal detachment. The locus of the gene responsible for the autosomal dominant form of FEVR (EVR1) has been assigned to 11q13-23. However, a detailed evaluation of the critical region has not been made. We present the results of linkage analysis of the EVR1 locus on 11q13-23 in 43 individuals belonging to seven unrelated families of Japanese origin. Multipoint analysis has shown that six families out of the seven are linked with 11q13-23 markers. Haplotype analysis reveals that the putative region is probably flanked by polymorphic markers D11S1362 and CHLC.GATA30G01, which are approximately 200 kb apart, although the recombination events in small families such as presented in this study should be interpreted cautiously.

Chromosomes, Human, Pair 11↗
PubMed2001

c-MET expression in myofibroblasts: role in autocrine activation and prognostic significance in lung adenocarcinoma.

Hepatocyte growth factor (HGF) plays important roles in tumor development and progression. It is currently thought that the main action of HGF is of a paracrine nature: HGF produced by mesenchymal cells acts on epithelial cells that express its receptor c-MET. In this investigation, we explored the significance of c-MET expression in myofibroblasts, both in culture and in patients with lung adenocarcinoma. We first showed that human myofibroblasts derived from primary lung cancer expressed c-MET mRNA and protein by reverse transcription-polymerase chain reaction and Western blot analysis. Proliferation of myofibroblasts was stimulated in a dose-dependent manner by exogenously added recombinant human HGF whereas it was inhibited in a dose-dependent manner by neutralizing antibody to HGF. The addition of HGF in the culture medium stimulated tyrosine phosphorylation of c-MET. The c-MET protein was immunohistochemically detected in myofibroblasts in the invasive area of lung adenocarcinoma. Finally, the prognostic significance of c-MET expression in stromal myofibroblasts was explored in patients with small-sized lung adenocarcinomas. c-MET-positive myofibroblasts were observed in 69 of 131 cases (53%). A significant relationship between myofibroblast c-MET expression and shortened patient survival was observed in a whole cohort of patients including all pathological stages (two-sided P: = 0.0089 by log-rank test) and in patients with stage IA disease (two-sided P: = 0.0019 by log-rank test). These data suggest that the HGF/c-MET system constitutes an autocrine activation loop in cancer-stromal myofibroblasts. This autocrine system may play a role in invasion and metastasis of lung adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided bronchoscopic barium marking.

BACKGROUND: Small lesions of the peripheral lung have been detected more frequently with the recent prevalence of computed tomography (CT). Identification of these lesions is indispensable for wedge resection performed by video-assisted thoracic surgery. Previous reports of marking techniques showed some failure and complications. We have developed a new marking technique and herein describe the efficacy of this technique: fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided bronchoscopic barium marking. METHODS: Twenty patients underwent this procedure for 21 small peripheral pulmonary lesions approximately 10 mm in size. RESULTS: All the lesions were successfully marked and identified during fluoroscopy-assisted thoracoscopy. They were resected with sufficient margins. There were no complications related to this procedure. The pathologic examination of these 21 lesions revealed primary lung cancer in 14, atypical adenomatous hyperplasia in four, a metastatic tumor in one, and a benign tumor in two. CONCLUSIONS: This procedure is both a reliable and minimally invasive technique in thoracoscopic wedge resection for small peripheral pulmonary lesions.

Adult↗
PubMed2001

Prognosis and survival after resection for bronchogenic carcinoma based on the 1997 TNM-staging classification: the Japanese experience.

BACKGROUND: A new TNM staging system was proposed, and the previous system was revised in 1997. METHODS: To evaluate the new TNM staging system for lung cancer, records of 3,043 lung cancer patients who underwent pulmonary resection at the National Cancer Center Hospital, Tokyo, were analyzed. RESULTS: With regard to clinical stages, 3 patients had occult carcinoma; 786 patients had stage IA disease; 759 patients, stage IB; 54 patients, stage IIA; 469 patients, stage IIB; 582 patients, stage IIIA; 211 patients, stage IIIB; and 179 patients, stage IV. The 5-year survival rates for the respective stages were 70.8% for stage IA, 44.0% for stage IB, 41.1% for stage IIA, 36.9% for stage IIB, 22.7% for stage IIIA, 20.1% for stage IIIB, and 21.6% for stage IV. In terms of postoperative stages, 7 patients were classified in stage 0, 610 in stage IA, 506 in stage IB, 114 in stage IIA, 432 in stage IIB, 702 in stage IIIA, 448 in stage IIIB, and 224 in stage IV. The 5-year survival rates were as follows: stage IA, 79.0%; stage IB, 59.7%; stage IIA, 56.9%; stage IIB, 45.0%; stage IIIA, 23.6%; stage IIIB, 16.5%; and stage IV, 5.1%. CONCLUSIONS: In the clinical stage, there were significant prognostic differences between stage IA and stage IB, stage IIB and IIIA, and stage IIIA and stage IIIB, but there was no significant difference in 5-year survival rates between stage IB and stage IIA, stage IIA, and IIB, and stage IIIB and stage IV. In the postoperative stage, there were significant differences in 5-year survival rates between each stage except for stage IB and stage IIA.

Adult↗
PubMed2001

Trisomy 21 as the sole acquired karyotypic abnormality in an adult patient with CD7-positive acute myeloid leukemia.

We report a unique case of acute myeloid leukemia (AML) in which trisomy 21 was the sole acquired karyotypic abnormality. The blasts were positive for myeloperoxidase, and phenotypic analysis of peripheral blood cells by flow cytometry demonstrated positivity for CD7, CD13, CD33, and CD34. chromosomal analysis of peripheral blood and bone marrow cells showed trisomy 21; however, that of the buccal mucosal membrane revealed a normal karyotype. A diagnosis of CD7+AML (M2) with trisomy 21 was diagnosed and the patient achieved complete remission following treatment with Japan Adult Leukemia Study Group-AML97 protocol. This is the first reported case of CD7+AML with trisomy 21 as the sole cytogenetic abnormality.

Adult↗
PubMed2001

Studies on selectin blocker. 9. SARs of non-sugar selectin blocker against E-, P-, L-selectin bindings.

As a part of study of selectin blockers, we have already reported that a non-sugar selectin antagonist (3) was successfully discovered using a computational screening (Hiramatsu, Y.; Tsukida, T.; Nakai, Y.; Inoue, Y.; Kondo, H. J. Med. Chem. 2000, 43, 1476). To investigate the SARs of compound 3 against E-, P-, and L-selectins, we synthesized the derivatives of compound 3 and evaluated their inhibitory activities toward selectin bindings. The structural diversity of compound 3 contained the following: (1) a modification of the spacer unit (4--7), (2) a modification of the tail unit (8--11), (3) a modification of the head unit (12--18). As a result, it was found that a non-sugar based selectin blocker (3) could be a potential lead compound for E-, P-, and L-selectin blockers and some of the derivatives showed broad and/or selective inhibitory activities toward the E-, P-, and L-selectins. In addition, it was found that the experimental evidence well supported that the computational screening using 3D-pharmacophore model could be useful methodology to find out a new lead for the several type of selectin blockers, which included a broad and/or a selective inhibitor.

Benzamides↗
PubMed2001

Localization of epidermal-type fatty acid binding protein in alveolar macrophages and some alveolar type II epithelial cells in mouse lung.

Almost all alveolar macrophages in the mouse lung were strongly immunoreactive for epidermal-type fatty acid binding protein. At the electron microscope level, the immunoreactive material was localized diffusely in the cytoplasm but not within the nucleus. A certain number of alveolar type II epithelial cells were also immunoreactive for the protein with variable immunointensity, while a substantial number of the type II cells were immunonegative. No immunoreactive interstitial fibroblasts were encountered. Based on the present findings, possible roles of epidermal-type fatty acid binding protein in the host-defence mechanism played by alveolar macrophages are suggested.

Animals↗
PubMed2001

Prostaglandin F2alpha upregulates interleukin-6 production in human gingival fibroblasts.

Prostaglandin F2alpha (PGF2alpha) is a bioactive lipid mediator which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2alpha in periodontal lesions are poorly understood. In the present study, we investigated the effect of PGF2alpha on interleukin (IL)-6 production in human gingival fibroblasts (HGF). PGF2alpha stimulated IL-6 production in a time- and concentration-dependent fashion. IL-1beta and tumor necrosis factor alpha (TNFalpha), proinflammatory cytokines, induced IL-6 production in a time-dependent manner, and PGF2alpha synergistically enhanced IL-6 production induced by IL-1beta and TNFalpha. IL-6 mRNA was expressed in PGF2alpha-stimulated HGF, and PGF2alpha increased IL-6 mRNA levels induced by IL-1beta and TNFalpha. Fluprostenol, a selective FP receptor agonist, could mimic PGF2alpha-induced IL-6 production. Since FP receptors are coupled to elevation of intracellular calcium and activation of protein kinase C (PKC), the mechanism of IL-6 production by PGF2alpha was investigated using TMB-8, an inhibitor of Ca2+ mobilization from intracellular stores, and calphostin C, an inhibitor of PKC. TMB-8 significantly suppressed PGF2alpha-induced IL-6 production, whereas calphostin C showed a stimulatory effect on PGF2alpha-induced IL-6 production. From these data, we suggest that PGF2alpha upregulates IL-6 production through FP receptors in HGF, that PGF2alpha synergistically enhances IL-6 production in IL-1beta- and TNFalpha-stimulated HGF, and that PGF2alpha-induced IL-6 production may be dependent on intracellular Ca2+ mobilization and be downregulated by PKC activation. PGF2alpha may be involved in the pathogenesis of periodontal disease by enhancing IL-6 levels in periodontal lesions.

Calcium↗
PubMed2001

Involvement of cyclooxygenase-2 in serum-induced prostaglandin production by human oral gingival epithelial cells.

The purpose of the present study was to investigate the involvement of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG) production by human oral gingival epithelial (OGE) cells stimulated with proinflammatory cytokines including interleukin(IL)-1alpha, IL-1alpha and tumor necrosis factor alpha (TNFalpha), and serum. Fetal bovine serum (FBS)-stimulated OGE cells produced significant levels of PGE2, whereas IL-1alpha, IL-1beta and TNFalpha could not induce significant PGE2 production. FBS induced PGE2 production in a dose- and time-dependent manner. NS-398, a selective COX-2 inhibitor, inhibited PGE2 production by FBS-stimulated cells as completely as indomethacin, a non-selective COX-1/COX-2 inhibitor. Expression of COX-2 protein in FBS-stimulated cells was increased, compared with that in unstimulated cells, whereas COX-1 protein expression was similar both in unstimulated and in FBS-stimulated cells. COX-2 mRNA was detected in FBS-stimulated cells, but not in unstimulated cells. We suggest that COX-2 is responsible for PG production by human OGE cells stimulated with serum and that OGE cells may be involved in PG production in periodontal lesions. Selective COX-2 inhibitors, which have the advantage of reduced gastric toxicity, may provide a useful approach to treatment of periodontal disease.

Analysis of Variance↗
PubMed2001

Upregulation of matrix metalloproteinase-1 production by prostaglandin F2alpha in human gingival fibroblasts.

In the present study, we investigated the effect of prostglandin F2alpha (PGF2alpha) and combination of PGF2alpha and interleukin(IL)-1beta on matrix metalloproteinase (MMP)-1 production in human gingival fibroblasts (HGF). PGF2alpha enhanced MMP-1 production in a dose-dependent manner in HGF. Combination of PGF2alpha and IL-1beta induced a synergistic increase of MMP-1 production in HGF. Furthermore, fluprostenol, a specific FP receptor agonist, increased MMP-1 production and induced a synergistic enhancement of IL-1beta-induced MMP-1 production in HGF, similar to PGF2alpha. FP receptor mRNA expression was detected in HGF, by reverse transcription-polymerase chain reaction. Northern blot analysis revealed that PGF2alpha enhanced MMP-1 mRNA expression in HGF and that PGF2alpha increased MMP-1 mRNA levels induced by IL-1beta. In conclusion, we suggest that PGF2alpha increases MMP-1 production in HGF and synergistically enhances MMP-1 production in IL-1beta-stimulated HGF. PGF2alpha may be involved in degradation of connective tissue in periodontal lesions.

Blotting, Northern↗
PubMed2001

Up-regulation of prostaglandin E receptor EP2 and EP4 subtypes in rat synovial tissues with adjuvant arthritis.

To evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis.

Animals↗
PubMed2001

Selective recruitment of CCR6-expressing cells by increased production of MIP-3 alpha in rheumatoid arthritis.

Infiltration of various types of leucocytes has been shown to play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Macrophage inflammatory protein-3 alpha (MIP-3 alpha) is a recently identified chemokine which is a selective chemoattractant for leucocytes such as memory T cells, naïve B cells and immature dendritic cells. In this study, we investigated the expression of MIP-3 alpha and its specific receptor CCR6 in the inflamed joints of patients with RA. Increased amounts of MIP-3 alpha were found by ELISA in synovial fluids (SF) of patients with RA. MIP-3 alpha was apparently detected in all synovial tissue specimens of RA patients (n = 6), but it could not be detected in that of osteoarthritis (OA) patients (n = 4). Expression of MIP-3 alpha was detected especially in the sublining layer, and infiltrating mononuclear cells in RA synovial tissue. Gene expression of MIP-3 alpha was also found in six out of 11 RA-synovial fluid cells by RT-PCR. Cultured synovial fibroblasts derived from either RA or OA patients were capable of producing MIP-3 alpha in response to IL-1 beta and TNFalpha in vitro. Furthermore, expression of CCR6 was found in infiltrating mononuclear cells in the cellular clusters and around the vessels of RA synovial tissue. These findings indicate that increased production of MIP-3 alpha may contribute to the selective recruitment of CCR6-expressing cells in RA.

Arthritis, Rheumatoid↗
PubMed2001

Endoscopically demonstrable esophageal changes after Helicobacter pylori eradication in patients with gastric disease.

BACKGROUND AND AIMS: An increased prevalence of reflux esophagitis has been reported following Helicobacter pylori (H. pylori) eradication in patients with duodenal ulcers in Western countries. However, it has remained unknown whether this might also appertain to individuals with other diseases. We therefore carried out this study to determine the effect of eradicating H. pylori infection in a series of Japanese patients. METHODS: Of a total of 203 H. pylori-positive patients successfully cured of infection, 82 cases (58 males, 24 females) with gastric disease, but not duodenal ulcers, were included in the present study; median age 56 years (range 18-80) and median follow up of 24 months (range 6-65). The patients were investigated clinically and endoscopically at regular intervals. RESULTS: Mild reflux esophagitis developed after eradication in three of 55 (5.5%) patients formerly without this condition, while it improved after eradication in five of 27 (18.5%) patients, with the disease endoscopically diagnosed prior to eradication. The estimated incidence of esophagitis within 3 years was 4.8% after cure of infection. Short segment Barrett's esophagus developed after eradication in six of 58 (10.3%) patients who did not have it prior to the therapy, while the condition did not improve in 24 patients affected before eradication. CONCLUSIONS: Endoscopic esophageal changes after H. pylori eradication in the present series of Japanese patients were relatively infrequent and mild. This therapeutic approach thus appears to be safe and unproblematic.

Adolescent↗
PubMed2001

The recognition and endoscopic treatment of early gastric and colonic cancer.

As the prognosis of both gastric and colonic cancer remains poor, the challenge is to detect lesions at an early and treatable stage. The benefit of early detection is not only improved survival, but also that patients may be treated with endoscopic mucosal resection, a low-cost, low-morbidity and low-mortality alternative to surgery. In spite of the increasing use of endoscopy in the West, we are not detecting as many early cancers as in Japan. This chapter will discuss the possible reasons for this discrepancy and give a practical guide to 'Japanese endoscopy techniques'. Finally, we have compiled a comprehensive review of the indications, techniques and complications of endoscopic mucosal resection. Throughout the chapter, controversies have been highlighted to give an insight into the limits of our knowledge and stimulate future research.

Colonic Neoplasms↗
PubMed2001

Pre-operative detection of malignant hepatic tumours: value of combined helical CT during arterial portography and biphasic CT during hepatic arteriography.

AIMS: The purpose of our study was to evaluate the observer performance with combined helical CT during arterial portography (CTAP) and biphasic CT hepatic arteriography (CTHA) in the pre-operative detection of malignant hepatic tumours. METHODS: Computed tomography images obtained in 41 patients with suspected hepatic tumours were retrospectively reviewed. In a blind fashion, three off-site, independent radiologists reviewed CTAP and early-phase CTHA combined for the first review, then late-phase CTHA was added for the second review. Statistical analysis was conducted on lesion-by-lesion and segment-by-segment bases; a total of 328 liver segments including 65 segments with 74 malignant hepatic tumours ranging in size from 5 to 100 mm (mean, 21.4 mm) were analysed. RESULTS: Sensitivity for detection of liver segments harbouring tumours of CTAP and biphasic CTHA combined (82%) was identical to that of CTAP and early-phase CTHA combined (82%). Specificity of CTAP and biphasic CTHA combined (93%) was greater than that of CTAP and early-phase CTHA combined (90%, P < 0.005). The mean confidence level for the 74 tumours significantly increased by adding late-phase CTHA (P < 0.0005). The mean confidence level for 100-142 benign perfusion abnormalities detected with CTAP and early-phase CTHA combined significantly decreased by adding late-phase CTHA (P < 0.0005). CONCLUSION: By combining late-phase CTHA with CTAP and early-phase CTHA information, the specificity for the detection of malignant hepatic tumours rises significantly, allowing more accurate preoperative tumour detection.

Aged↗
PubMed2001

Metastatic tumors to the stomach: analysis of 54 patients diagnosed at endoscopy and 347 autopsy cases.

BACKGROUND AND STUDY AIMS: There have been several published reports on metastatic lesions in the stomach, but the numbers of cases have been limited due to the low frequency of the condition. The present study examined the clinicopathological features of metastatic tumors in the stomach from distant sites in a large series of cases. PATIENTS AND METHODS: A total of 389 patients with gastric metastases from solid malignant tumors were examined between 1968 and 1998 at our institution. Of these, 347 were identified from a series of 6380 autopsy cases; 54 patients were diagnosed endoscopically while alive, 12 of whom had confirmation of the condition at autopsy. RESULTS: In the endoscopically diagnosed cases, the metastases presented as solitary (65%) or multiple lesions (35 %), and were more frequently located in the middle or upper third of the stomach. Although the endoscopic appearance often resembled that of submucosal tumor (51%) or primary gastric cancer (39%), the final diagnosis was easily obtained in over 90% of cases from endoscopic biopsies. In two cases of lung cancer and breast cancer, gastric metastases were found before the primary tumors. In the autopsy cases with solid malignancies, metastatic lesions to the stomach were found in 5.4%, and the lung, breast, and esophagus were common primary sites. Malignant melanoma was the most frequent tumor to metastasize to the stomach (29.6%). CONCLUSIONS: Since metastatic lesions to the stomach are rare, the above characteristics of the lesions should be borne in mind, and biopsies should be taken for precise diagnosis during endoscopic examinations.

Adult↗