Search PubMed⌕ Search

Biomedical subjects

S Kudoh

Publications and source records attributed to S Kudoh.

At least 109 records · Page 6Linked to original sources
PubMed1999

Augmented proliferation of human alveolar macrophages after allogeneic bone marrow transplantation.

After allogeneic bone marrow transplantation (allo-BMT), recipient alveolar macrophages (AM) are gradually replaced by AM of the donor origin. An influx of mononuclear phagocytes of donor origin to the lung is responsible for the repopulation, but the detailed kinetics remain unclear. We therefore studied 24 BMT recipients who underwent bronchoalveolar lavage (BAL) from 24 to 83 days after BMT. AM cell number, size, morphology, proliferating ability, and genotype of AM were measured. Before day 50, the number and size of AM in BAL fluid were similar to those of normal nonsmokers. However, after day 50, the mean number of AM increased threefold and the mean cell size decreased due to the increase of small AM. These small cells are presumably of donor origin based on DNA fingerprinting analysis and based on fluorescence in situ hybridization for the Y chromosome in a sex-mismatched case. Immunohistochemistry and cell cycle analysis demonstrated that the increase in AM number coincided with a remarkable increase of AM expressing proliferating cell nuclear antigen, suggesting that small AM are proliferating. This is the first report representing that augmented proliferation of donor AM in situ may contribute to the reconstitution of AM population after BMT.

Adolescent↗
PubMed1999

Combination effects of TAS-103, a novel dual topoisomerase I and II inhibitor, with other anticancer agents on human small cell lung cancer cells.

PURPOSE: TAS-103 [6-((2-(dimethylamino) ethyl)amino)-3-hydroxy-7H-iindeno(2,1-c)quinolin-7-one dihydrochloride] is a newly synthesized dual inhibitor of topoisomerase I and II. Since anticancer drugs are used in combination with other drugs for effective chemotherapy, we investigated the cytotoxic effect of TAS-103 in combination with other conventional anticancer agents, such as cisplatin, vindesine, doxorubicin, 5-fluorouracil, and the antitopoisomerase inhibitors SN-38 and etoposide in vitro. METHODS: Inhibition of the growth of the human small-cell lung cancer cell line SBC-3 was evaluated using the tetrazolium dye (MTT) assay. Drug interactions were evaluated by isobologram analysis and the determination of combination indices supplemented by a three-dimensional model. RESULTS: Simultaneous use of TAS-103 and cisplatin had a supraadditive effect, but combinations of TAS-103 with other drugs had an additive or marginally subadditive effect. Three-dimensional model analysis added more information about the synergistic concentration ranges of two drugs (cisplatin 200-400 nM and TAS-103 7 10 nM). Sequential use of TAS-103 and cisplatin had only an additive effect. CONCLUSION: These results suggest that the concomitant use of TAS-103 and cisplatin has a greater cytotoxic effect on cancer cells than single drug use, and may provide a beneficial effect in the treatment of small-cell lung cancer.

Aminoquinolines↗
PubMed1999

Association of diffuse panbronchiolitis with microsatellite polymorphism of the human interleukin 8 (IL-8) gene.

Diffuse panbronchiolitis (DPB) is a distinctive chronic inflammatory lung disease predominantly found in Asian populations. Although its etiology is unknown, DPB is considered to be a multifactorial disease of whose susceptibility is determined by genetic predisposition unique to Asians. We and others have previously reported that the B*5401 allele of the human leukocyte antigen (HLA)-B gene or a closely linked gene in the HLA region on 6p21.3 is one of the major genetic factors in susceptibility to this disease. However, the association with B*5401 is not absolute and the contribution of other genetic or environmental factors should also be considered. Here, four candidate genes that are postulated to play a role in the pathophysiology of DPB, namely, RON-kinase, CYP3A4, motilin, and interleukin (IL)-8, were chosen, and association studies between microsatellite markers at these loci and DPB were conducted. We demonstrated the presence of a specific allele at the IL-8 locus was associated with the disease (c2 = 9.13; P = 0.0025; corrected P [Pc] < 0.05). Although further studies are needed to examine whether neutrophil accumulation in the airways of patients with DPB is controlled by a possible genetic variation of IL-8 or other chemokine genes located in the region 4q12-q13, our data suggest that genes other than those of the HLA system may also contribute to a genetic predisposition to DPB.

Asian People↗
PubMed1999

Alteration of the PTEN/MMAC1 gene locus in primary lung cancer with distant metastasis.

The PTEN/MMAC1 gene located at 10q23, has been proposed to be a tumor suppressor gene. To determine the involvement of alteration of the PTEN/MMAC1 gene in carcinogenesis and the progression of primary lung cancers, we analyzed tumor samples of primary and distant metastatic sites and normal lung tissue samples of 30 patients with advanced lung cancer with distant metastasis. The tissues were analyzed for allelic deletion and mutational inactivation of PTEN/MMAC1 by loss of heterozygosity (LOH) analysis, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), and direct sequence analysis. LOH of the PTEN/MMAC1 locus was common in each histologic type of primary lung cancer. In this study, the overall allelic deletion rate was 33.3% (7/21). Allelic loss at the primary site and that at the metastatic site of each patient, were identical; in most cases, it seemed that the allelic loss had occurred before metastasis. Sequence analysis of the PTEN/MMAC1 gene revealed a G to C substitution located 8 bp upstream of the coding region of exon 1 and which seems to be a polymorphism, in 4 of the 30 cases. Somatic mutations of the PTEN/MMAC1 gene were not identified in any of the tumors at the primary and metastatic sites. These data indicate that point mutations in the PTEN/MMAC1 gene are probably not an important factor in tumorigenesis and the progression of a major subset of lung cancers. Due to frequent allelic loss at the PTEN/MMAC1 locus occurring at a stage earlier than the metastatic process, alternative mechanisms in which the remaining allele is inactivated such as methylation or homozygous deletion of a small region of the gene that can not be detected by the usual analysis, or alteration of other important tumor suppressor genes lying close to the PTEN/MMAC1 gene on 10q23, may be involved in the tumorigenesis of lung cancers of all histologic subtypes.

Alleles↗
PubMed1999

Contribution of TAP genes to genetic predisposition for diffuse panbronchiolitis.

Diffuse panbronchiolitis is a chronic obstructive pulmonary disease found in Asian populations. Although diffuse panbronchiolitis is considered to be a multifactorial disease of unknown etiology, the disease susceptibility appears to be determined by a genetic predisposition unique to Asians. An earlier study showed that human leukocyte antigen (HLA)-B54 predominantly found in East Asians was strongly associated with the disease. A possible interpretation of this association is that the class I molecule or class I antigen presenting system is directly involved in its pathogenesis. Recent observations in which impaired expression of class I molecules causes a syndrome resembling diffuse panbronchiolitis further prompted us to test this possibility. Genes of the molecules implicated in the class I pathway, TAP1, TAP2 and LMP2, which are located in the HLA region of the sixth chromosome were analyzed in 76 patients with diffuse panbronchiolitis and 120 normal controls. The combination of Ala-665 and Gln-687 in exon 11 of the TAP2 gene was associated with the disease (P=0.0028, Pc<0.05). Although this positive association might be partly explained by linkage disequilibrium with HLA-B*5401, this TAP2 variation was associated with the disease even in the B*5401-negative subgroup. On the other hand, the His-60 substitution within the LMP2 gene exhibited a negative association with the disease. This negative association, however, could be explained by a strong linkage disequilibrium with HLA-B44 which showed a negative association with the disease in the previous study. These results support the notion that diffuse panbronchiolitis is influenced by genetic factors in the HLA region. Besides the class I gene itself, genes relevant to the class I antigen presenting system might contribute to its genetic predisposition.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Phase I/II study of weekly irinotecan and concurrent radiation therapy for locally advanced non-small cell lung cancer.

A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities, and the response rate of irinotecan administered weekly with concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, surgically unresectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) were enrolled. Irinotecan was administered as a 90 min intravenous infusion once weekly for 6 weeks. The starting dose was 30 mg m(-2) and dose escalation was done in 15 mg m(-2) increments. Dose-limiting toxicity was defined as grade 3 nonhaematologic toxicity (excluding nausea, vomiting and alopecia) or grade 4 haematologic toxicity according to the WHO criteria. Radiation was delivered to the primary tumour and regional lymph nodes (40 Gy), followed by a boost to the primary tumour (20 Gy). Twenty-seven patients were entered into this study at three irinotecan dose levels (30, 45 and 60 mg m(-2)). Twenty-six eligible patients were evaluated for toxic effects and clinical outcome. Severe oesophagitis, pneumonitis, and diarrhoea occurred at 45 and 60 mg m(-2). Three of the five patients given 60 mg m(-2) developed grade 3 or 4 oesophagitis and pneumonitis. In addition, one patient died of pneumonitis after completing therapy at 45 mg m(-2) in the phase II study. The objective response rate was 76.9% (95% CI, 53.0-88.9%). Oesophagitis, pneumonitis, and diarrhoea are the dose-limiting toxicities of weekly irinotecan combined with thoracic irradiation. The maximum tolerated dose and the dose for the phase II study were 60 and 45 mg m(-2) wk(-1), respectively. This combined therapy for locally advanced non-small cell lung cancer is promising and shows acceptable toxicity.

Adenocarcinoma↗
PubMed1999

Protein expression of cell cycle regulator, p27Kip1, correlates with histopathological grade of non-Hodgkin's lymphoma.

The protein p27Kip1 is one of the cyclin-dependent kinase inhibitors that are known to play important roles in the regulation of cell-cycle progression. Low levels of p27 expression in malignant cells are associated with poor prognosis in patients with breast, lung, colorectal and gastric cancers. To determine the relation of cyclin-dependent kinase inhibitors to histopathological grades of B-cell non-Hodgkin's lymphomas, the expression of p27, cyclin D1 and cyclin E in lymph node tissues was investigated in 56 patients with B-cell non-Hodgkin's lymphomas by western blotting and immunohistochemical techniques. High levels of p27 expression were observed in most lymph node tissue samples (93%) obtained from patients with low grade B-cell non-Hodgkin's lymphomas, while expression was low in lymph node tissue taken from all patients with intermediate and high grade B-cell non-Hodgkin's lymphomas. The difference in p27 expression in lymphoma tissues was significant among the different histopathological grades of B-cell non-Hodgkin's lymphomas (P<0.01). The analysis of the survival time of patients showed that the reduction of p27 expression correlated with poor prognosis. Cyclin D1, showed a high level of expression in mantle cell lymphomas and high grade B-cell non-Hodgkin's lymphomas. Cyclin E showed limited expression in 18 of 31 lymphoma tissues. Both cyclin D1 and E protein expression were not significantly different among the grades of B-cell non-Hodgkin's lymphomas. These results demonstrate that the level of p27 expression in lymphoma tissue is an important parameter in the classification of B-cell non-Hodgkin's lymphomas and in the prediction of prognosis.

Blotting, Western↗
PubMed1999

Expression of a germination-specific amidase, SleB, of Bacilli in the forespore compartment of sporulating cells and its localization on the exterior side of the cortex in dormant spores.

A germination-specific amidase of bacilli is a major spore-lytic enzyme that is synthesized with a putative signal sequence and hydrolyses spore cortex in situ. The sleB gene encoding this amidase in Bacillus subtilis and Bacillus cereus was expressed in the forespore compartment of sporulating cells under the control of sigmaG, as shown by Northern blot and primer extension analyses. The forespore-specific expression of B. subtilis sleB was further indicated by the forespore-specific accumulation of a SleB-green fluorescent protein fusion protein from which a putative secretion signal of SleB was deleted. Immunoelectron microscopy with anti-SleB antiserum and a colloidal gold-immunoglobulin G complex showed that the enzymes from both Bacillus species are located just inside the spore coat layer in the dormant spore, and in the dormant spore, the amidases appear exist in a mature form lacking a signal sequence. These results indicate that SleB is translocated across the forespore's inner membrane by a secretion signal peptide and is deposited in cortex layer synthesized between the forespore inner and outer membranes. The peripheral location of the spore-lytic enzymes in the dormant spore suggests that spore germination is initiated at the exterior of the cortex.

Amidohydrolases↗
PubMed1999

Bone morphogenetic proteins induce cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase TAK1 and cardiac transcription factors Csx/Nkx-2.5 and GATA-4.

Bone morphogenetic proteins (BMPs) have been shown to induce ectopic expression of cardiac transcription factors and beating cardiomyocytes in nonprecardiac mesodermal cells in chicks, suggesting that BMPs are inductive signaling molecules that participate in the development of the heart. However, the precise molecular mechanisms by which BMPs regulate cardiac development are largely unknown. In the present study, we examined the molecular mechanisms by which BMPs induce cardiac differentiation by using the P19CL6 in vitro cardiomyocyte differentiation system, a clonal derivative of P19 embryonic teratocarcinoma cells. We established a permanent P19CL6 cell line, P19CL6noggin, which constitutively overexpresses the BMP antagonist noggin. Although almost all parental P19CL6 cells differentiate into beating cardiomyocytes when treated with 1% dimethyl sulfoxide, P19CL6noggin cells did not differentiate into beating cardiomyocytes nor did they express cardiac transcription factors or contractile protein genes. The failure of differentiation was rescued by overexpression of BMP-2 or addition of BMP protein to the culture media, indicating that BMPs were indispensable for cardiomyocyte differentiation in this system. Overexpression of TAK1, a member of the mitogen-activated protein kinase kinase kinase superfamily which transduces BMP signaling, restored the ability of P19CL6noggin cells to differentiate into cardiomyocytes and concomitantly express cardiac genes, whereas overexpression of the dominant negative form of TAK1 in parental P19CL6 cells inhibited cardiomyocyte differentiation. Overexpression of both cardiac transcription factors Csx/Nkx-2.5 and GATA-4 but not of Csx/Nkx-2.5 or GATA-4 alone also induced differentiation of P19CL6noggin cells into cardiomyocytes. These results suggest that TAK1, Csx/Nkx-2.5, and GATA-4 play a pivotal role in the cardiogenic BMP signaling pathway.

Bone Morphogenetic Proteins↗
PubMed1999

Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage.

We analyzed adaptation mechanisms regulating systemic inflammatory response of the stressed body by using an experimental challenge of repeated exercise bouts and accompanying muscle inflammation. Eight untrained men bicycled at 90 W for 90 min, 3 days in a row. Exercise induced peripheral neutrophilia with a leftward shift of neutrophil nucleus and neutrophil priming for oxidative activity determined by luminol-dependent chemiluminescence. Plasma growth hormone and interleukin-6 rose significantly after exercise and were closely correlated with the neutrophil responses. Serum creatine kinase and myoglobin levels as muscle damage markers rose after exercise in "delayed onset" and were closely correlated with the preceding neutrophil responses. These exercise-induced responses were strongest on day 1, but the magnitude gradually decreased with progressive daily exercise. In contrast, the magnitude of catecholamine responses to exercise sessions gradually rose, possibly suppressing neutrophil oxidative responses. These results indicate that stress-induced systemic release of bioactive substances may determine neutrophil mobilization and functional status, which then may affect local tissue damage of susceptible organs.

Adult↗
PubMed1999

Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer.

PURPOSE: A phase III study was performed to determine whether concurrent or sequential treatment with radiotherapy (RT) and chemotherapy (CT) improves survival in unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were assigned to the two treatment arms. In the concurrent arm, chemotherapy consisted of cisplatin (80 mg/m(2) on days 1 and 29), vindesine (3 mg/m(2) on days 1, 8, 29, and 36), and mitomycin (8 mg/m(2) on days 1 and 29). RT began on day 2 at a dose of 28 Gy (2 Gy per fraction and 5 fractions per week for a total of 14 fractions) followed by a rest period of 10 days, and then repeated. In the sequential arm, the same CT was given, but RT was initiated after completing CT and consisted of 56 Gy (2 Gy per fraction and 5 fractions per week for a total of 28 fractions). RESULTS: Three hundred twenty patients were entered onto the study. Pretreatment characteristics were well balanced between the treatment arms. The response rate for the concurrent arm was significantly higher (84. 0%) than that of the sequential arm (66%) (P =.0002). The median survival duration was significantly superior in patients receiving concurrent therapy (16.5 months), as compared with those receiving sequential therapy (13.3 months) (P =.03998). Two-, 3-, 4-, and 5-year survival rates in the concurrent group (34.6%, 22.3%, 16.9%, and 15.8%, respectively) were better than those in the sequential group (27.4%, 14.7%, 10.1%, and 8.9%, respectively). Myelosuppression was significantly greater among patients on the concurrent arm than on the sequential arm (P =.0001). CONCLUSION: In selected patients with unresectable stage III NSCLC, the concurrent approach yields a significantly increased response rate and enhanced median survival duration when compared with the sequential approach.

Adult↗
PubMed1999

[A clinical study of bladder cancer in adolescent patients].

PURPOSE: We have reviewed clinical characteristics of bladder cancer in adolescent patients. MATERIALS AND METHODS: Between 1978 and 1997, we have experienced eight bladder cancer patients of 7 men and 1 woman under 30 years old. Two patients were less than 20 years old and six patient were more than 20 years old. We have reviewed initial symptoms, diagnostic methods, cystoscopic findings, methods of treatment, pathological findings, and prognosis of these patients. RESULTS: The most common chief complaint was asymptomatic macroscopic hematuria. Cystoscopically, all tumors were papillary and solitary except in one case. All of tumors were superficial transitional cell carcinomas and treated with transurethral resection (TUR). Although the tumors in patients of less than 20 years old were pathologically grade 1 and 2, two cases of grade 3 tumors were found in patients more than 20 years old. The prognosis of these patients were good, for none of them was dead and the recurrence rate after TUR was 12.5% (1/8). CONCLUSIONS: We considered that characteristics of bladder cancer in adolescent patients were low stage, low grade, and good prognosis. But it was found that high grade tumors were contained in patients more than 20 years old.

Adolescent↗
PubMed1999

[Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. 3. Current status of tuberculosis patient care in university hospitals and general hospitals in Japan].

A recent epidemiological survey has revealed that the incidence of Mycobacterium tuberculosis (TB) patients in Japan has just increased again after four decades of decline. In fact, recently there have been numerous reports of TB outbreaks in health-care facilities. Although our medical school hospital does not have TB isolation rooms, we have to take care of more than a few TB patients, most of whom have been transferred from primary care clinics. Although, some of these TB patients have highly infectious (sputum smear positive), most of them have not been diagnosed as having highly infectious TB, and therefore, some of their patients ultimately have to be retransferred to a TB hospital. This indicates that most physicians in primary care clinics have little knowledge about TB. This may be partly because of lack of training regarding TB during their medical student days and residencies. To elucidate current TB patient care status in university hospitals in Japan, a survey of physicians working in such hospitals was conducted from September 1997 to January 1998. The survey (questionnaire) revealed that the majority (76%) of these hospitals do not have TB isolation rooms. However, these hospitals have to take care of TB patients in their outpatient clinics and sometimes on their wards because the patients have serious complications that can not be treated in ordinary TB hospitals. The survey also showed that for this reason and from an educational point of view, the majority of the physicians (90%) working in these hospitals thought that university hospitals should have isolation rooms for such patients. Another questionnaire revealed that few physicians and nurses in university hospitals have sufficient experiences in taking care of TB patients. This situation may have been responsible for producing physicians with little knowledge about TB. Recent scientific advances have made it possible to construct TB isolation rooms in ordinary wards by means of separate ventilation systems. Although combatting TB requires a variety of strategies, appropriate education for both medical students and residents using isolation rooms in university hospitals may be an effective means of preventing spread of TB, and this approach may also increase awareness concerning the prevention of TB outbreaks in hospitals and health-care facilities.

Hospitals, General↗
PubMed1999

[The role of angiotensin II in the development of cardiovascular remodeling].

We examined the role of AT1 in the development of cardiovascular remodeling using AT1a knockout (KO) mice. 1. Pressure overload and mechanical stretch induced hypertrophic responses in KO and wild type (WT) cardiomyocytes (CM). Stretch activated MAPK through PKC in WT CM and through tyrosine kinase in KO CM. 2. The number of ventricular premature beats and tachycardia was larger in WT mice than KO mice. 3. Left ventricular remodeling after myocardial infarction was more remarkable in WT mice than KO mice. 4. Vascular injury induced neointimal formation in KO mice as well as in WT mice.

Angiotensin II↗
PubMed1999

[Diffuse panbronchiolitis: DPB].

Diffuse panbronchiolitis (DPB) is a chronic inflammatory airway disease which was lethal in the past despite combined treatment with antibiotics and the use of supportive therapies such as oxygen administration. Diagnosis of DPB is performed according to the diagnostic criteria that include major items: symptoms, existence of parasinusitis, chest radiographic findings, minor items: physical signs (coarse crackles), pulmonary functions and blood gas tests, and elevated titers of cold hemagglutinin. Pathological feature shows thickness of the wall of respiratory bronchiole with infiltration of lymphocytes, plasma cells, and foamy histiocytes expanded into the peribronchiolar area. Many of these bronchiolitis progress respiratory failure with bronchiectasis in advanced stage. Recently, DPB was interested in genetic predisposition because of high accumulation in the East Asia with the same HLA haplotype. Low-dose of erythromycin (400-600 mg/day) is a authorized therapy to improve the survival time of patients with DPB. 14-membered ring macrolides other than erythromycin also improve the survival of DPB patients.

Anti-Bacterial Agents↗
PubMed1999

[Churg-Strauss syndrome with pulmonary eosinophilia and intrapulmonary lymph nodes 2 years before the onset of vasculitis].

We report a case of a 55-year-old man who had been treated for bronchial asthma diagnosed at the age of 51. One year following diagnosis, chest X-ray films disclosed nodular shadows. Biopsy specimens obtained by video-assisted thoracoscopic surgery were histopathologically identified as intrapulmonary lymph nodes. Three years after the initial diagnosis, the patient experienced sensory disturbance of the lower extremities, low-grade fever, and weight loss. At this point he was admitted to our hospital. On admission, physical examination and clinical investigations showed peripheral eosinophilia and signs of vasculitis. Specimens obtained by transbronchial lung biopsy and bronchoalveolar lavage showed strong evidence of tissue damage with infiltration of eosinophils but no evidence of necrotizing vasculitis or extra-vascular granuloma. Churg-Strauss syndrome (CSS) was diagnosed, and treatment was initiated with prednisolone at a dose of 60 mg/day. Except for the sensory disturbances in the lower extremities, after a few days of treatment the patient's symptoms subsided and his clinical data improved. This case was clinically important because pulmonary eosinophilic infiltration into vessel walls was confirmed a year after the diagnosis of bronchial asthma, and 2 years before the patient demonstrated signs of vasculitis. Further, it was a very rare case of CSS in which intrapulmonary lymph nodes had developed beneath the visceral pleura despite the absence of a history of heavy smoking, thus suggesting continuous stimulation by some as yet unknown antigen.

Asthma↗