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S Tada

Publications and source records attributed to S Tada.

At least 37 records · Page 2Linked to original sources

The role of fibronectin in bronchoalveolar lavage fluid of asthmatic patients.

Allergic and chronic inflammation of the airway is regarded as the main pathogenesis of bronchial asthma, in which adhesion of inflammatory cells requires the expression of adhesion molecules. Thus, to clarify the role of fibronectin (FN) in the airway inflammation of bronchial asthma, FN levels in plasma and bronchoalveolar lavage fluid (BALF) from bronchial asthmatics were determined. FN concentrations in plasma and BALF were measured by enzyme-linked immunosorvent assay (ELISA) in 17 asthmatic patients and 10 healthy controls to elucidate the role of FN in allergic inflammation. The mean FN/albumin (Alb) level in the BALF of asthmatic patients was 2.973 micrograms/mg, which was significantly higher than that of healthy controls (0.727 microgram/mg). Non-atopic asthmatics showed a significantly higher level of FN in their BALF in comparison with atopic asthmatics, although the ratio of FN to albumin showed no significant difference. FN levels in BALF correlated significantly with total cell density (r = 0.71, P < 0.05) and alveolar macrophage density (r = 0.64, P < 0.05). FN levels in plasma did not correlate with those in BALF. In conclusion, increased FN in BALF, which was produced locally in the airways of asthmatic patients, is actively involved in the regulation of allergic inflammation.

Adult↗

Plasma fibronectin in asthmatic patients and its relation to asthma attack.

This study investigated the relation between asthma attacks and levels of plasma fibronectin (FN) and serum eosinophilic cationic protein (ECP) in patients with bronchial asthma in order to clarify the role of FN in the airway inflammation of bronchial asthma. Plasma levels of FN were significantly higher (P < 0.025) in patients with bronchial asthma than in healthy controls. They were also significantly higher (P < 0.05) in non-atopic asthmatics than in atopic asthmatics. Furthermore, plasma FN was lower during the attack than the non-attack stage (P < 0.025), and a significant increase of plasma FN was noted (P < 0.05) in asthmatics who had more severe and more frequent attacks. Serum levels of ECP were significantly higher during the attack than the non-attack stage (P < 0.005). An increase of plasma FN in the non-attack stage after attacks showed a significant correlation (P < 0.05) with a decrease of serum ECP. These observations clearly indicate that the decrease in plasma FN associated with attacks is closely related to aggravation of airway inflammation, and that the increase in plasma FN in the non-attack stage reflects chronic airway inflammation. These results suggest that the fluctuation in plasma levels of FN may be one of the factors affecting allergic inflammation and attacks in bronchial asthma.

Acute Disease↗

Dimethyl sulfoxide inhibits dimethylnitrosamine-induced hepatic fibrosis in rats.

We studied the preventive effects of dimethyl sulfoxide (DMSO) on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant decrease in body and liver weight. Oral DMSO (2 ml/kg daily for 4 weeks) essentially prevented this DMN-induced body and liver weight loss with no major side effects. DMSO suppressed the induction of hepatic fibrosis, as determined by histological evaluation, and reduced hepatic hydroxyproline. It also suppressed the expression of mRNA for type I collagen in the liver. Because hepatic stellate cells (HSC) are the major cellular source of the collagen in hepatic fibrosis, we examined the effects of DMSO on collagen production in vitro using rat primary HSC culture. However, it was found that DMSO did not inhibit the collagen production in vitro. We next evaluated the effects of DMSO on tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) production by Kupffer cells, because these factors represent major activator of HSC, and because monocyte-macrophage infiltration has been implicated as being pathogenetically important for hepatic fibrosis induced by DMN. DMSO inhibited lipopolysaccharide (LPS)-induced TNFalpha and NO production, and reduced TNFalpha mRNA levels. DMSO also suppressed the LPS-induced nuclear factor kappa B activation in a murine macrophage-like cell line. These results suggest that the inhibitory effects of DMSO on hepatic fibrosis may be primarily exerted via blocking of DMN-induced inflammation. These results also implied that DMSO may be potentially useful for preventing the development of hepatic fibrosis.

Animals↗

Color/power Doppler sonographic differential diagnosis of superficial lymphadenopathy: metastasis, malignant lymphoma, and benign process.

OBJECTIVE: Differentiation of lymph nodes as metastasis, malignant lymphoma, and benign lesions by gray scale and color/power Doppler ultrasonography has been reported. In this study we sought to determine patterns of abnormal vascularity, the relationship between diagnostic criteria and node size, and which vessel in the node was best suited for Doppler spectral analysis. Extrahilar vessels, defined as vessels entering through the lymphatic surface and not through the hilus, were also investigated. METHODS: One hundred twenty-nine nodes were examined by color/power Doppler ultrasonography. RESULTS: Extrahilar vessels were seen in 85.4% of metastatic, 40.5% of lymphomatous, and 7.7% of benign nodes regardless of node size. The mean pulsatility index and resistive index values of metastatic nodes were higher than those of benign nodes regardless of their size. Those of lymphoma were intermediate compared with the others. CONCLUSIONS: A pulsatility index greater then 1.3 and a resistive index greater than 0.72 suggested malignancy as measured from any vessel.

Breast Neoplasms↗

[Prognosis of subacutely progressive interstitial pneumonia depends on the presence of focal usual interstitial pneumonia].

A retrospective follow-up study was conducted on patients with subacutely progressive interstitial pneumonia who underwent surgical biopsy. Pathologically, they were subclassified into subacute interstitial pneumonia (SIP) and SIP + F, which consisted of an SIP lesion and a focal usual interstitial pneumonia. The SIP group consisted of 35 cases and the SIP + F group, of 15 cases. The majority of patients in both groups were female and complained of dyspnea. Both groups showed increased neutrophil counts (8.8%, 6.3%), eosinophils (6%, 5.6%), and lymphocytes (43.1%, 42.3%) in bronchoalveolar lavage. Chest radiography generally demonstrated predominant lower lobe involvement together with shrinkage in both groups, and differentiation of the two was difficult before biopsy. All but one improved temporarily with steroid therapy, or spontaneously, in both groups. On further observation after temporary improvement, 27 cases (82%), did not show any worsening and 6 cases (18%) showed worsening (including death) in the SIP group, while 6 cases (43%) showed no worsening, though 8 cases (57%) worsened in the SIP + F group. Deaths in either group that were not related to the original diseases were excluded from the statistical analysis. We concluded that the presence of focal usual interstitial pneumonia in SIP lesions affects prognosis in patients with subacutely progressive interstitial pneumonia.

Aged↗

[Dose finding study of paclitaxel and carboplatin for ovarian cancer (JKTB)].

We conducted a dose-finding study for combination therapy of paclitaxel (Taxol; TXL) and carboplatin (Paraplatin; CBDCA). TXL is a novel plant-derived anticancer agent that is a diterpene derivative possessing the taxane ring. The subjects were patients with ovarian carcinoma, who were evaluated by a modified Fibonacci method. The dosage of TXL was 150 to 180 mg/m2. CBDCA was administered by dose escalation from AUC = 4 to 7. The administration schedule was as follows. Pre-medication was administered before TXL was given. TXL was then administered by intravenous infusion over 3 hours, followed by CBDCA. The dose of CBDCA was determined using the Calvert formula: [AUCX (GFR + 25)]. GFR was calculated with the Jelliffe equation. The non-hematological toxicities observed in 15 eligible cases were mainly grade 1, with no grade 3 or above, and no increase in severity was observed with stepping up. The hematological toxicities were grade 3 leukopenia in 5 of 15 cases, neutropenia in 5 cases and thrombocytopenia in 0 cases. No grade 4 toxicity was observed. The lowest counts of leukocytes and neutrophils were reached after 10.8 and 11.7 days, respectively. The toxicities were reversible in most cases with subsequent recovery. The above findings indicate that the recommended dosages for TJ therapy for Japanese ovarian cancer patients should be TXL 180 mg/m2 and CBDCA at a target of AUC = 6.

Adolescent↗

huASH1 protein, a putative transcription factor encoded by a human homologue of the Drosophila ash1 gene, localizes to both nuclei and cell-cell tight junctions.

During animal development, regions of the embryo become committed to position-specific identities, which are determined by spatially restricted expression of Hox/homeotic genes. This expression pattern is initially established by the activity of the segmentation genes and is subsequently maintained during the proliferative stage through the action of transcription factors encoded by the trithorax (trx) and Polycomb (Pc) groups of genes. trithorax (trx)and ash1 (absent, small, or homeotic 1) are members of the Drosophila trx group. Their products are associated with chromosomes and are believed to activate transcription of target genes through chromatin remodeling. Recently, we reported molecular studies indicating that TRX and ASH1 proteins act in concert to bind simultaneously to response elements located at close proximity within the same set of target genes. Extension of these and other studies to mammalian systems required identification and cloning of the mammalian homologue of ash1 (the mammalian homologue of trx, ALL-1, was previously cloned). We have identified a human expressed sequence tag (EST) clone with similarity to the SET domain of Drosophila ASH1, and used it to clone the human gene. huASH1 resides at chromosomal band 1q21. The gene is expressed in multiple tissues as an approximately 10.5-kb transcript and encodes a protein of 2962 residues. The protein contains a SET domain, a PHD finger, four AT hooks, and a region with homology to the bromodomain. The last region is not present in Drosophila ASH1, and as such might confer to the human protein a unique additional function. Using several anti-huASH1 Ab for immunostaining of cultured cells, we found that the protein is distributed in intranuclear speckles, and unexpectedly also in intercellular junctions. Double-immunofluorescence labeling of huASH1 and several junctional proteins localized the huASH1 protein into tight junctions. The significance of huASH1 dual location is discussed. In particular, we consider the possibility that translocation of the protein between the junctional membrane and the nucleus may be involved in adhesion-mediated signaling.

Amino Acid Sequence↗

A p160ROCK-specific inhibitor, Y-27632, attenuates rat hepatic stellate cell growth.

BACKGROUND/AIMS: p160ROCK, a serine/threonine protein kinase, is a direct RhoA target mediating RhoA-induced assembly of focal adhesions and stress fibers. Recently, Rho signaling pathways were reported to play an important role in the activation of rat hepatic stellate cells (HSC). The aim of this study was to investigate the mechanism of action of a p160ROCK-specific inhibitor, Y-27632, on cultured rat HSC. METHODS: HSC were isolated from normal rat livers and cultured on fibronectin-coated dishes. The cell morphology and actin cytoskeleton were studied with phase contrast and fluorescence microscopy, respectively. Immunoblot analysis was used to examine phosphorylation of focal adhesion kinase and extracellular signal-regulated kinase, and the expression of cell cycle-associated proteins. HSC proliferation was measured by quantitating the percentage of cells that exhibited nuclear incorporation of 5-bromodeoxyuridine. Type I collagen gene expression and accumulation in HSC culture media were evaluated by Northern blot and enzyme-linked immunosorbent assay, respectively. RESULTS: Y-27632 consistently blocked cell spreading and suppressed RhoA-induced formation of stress fibers in HSC. In addition, Y-27632 inhibited phosphorylation of focal adhesion kinase and extracellular signal-regulated kinase. Cells treated with Y-27632 failed to proliferate, in contrast to untreated spread cells. This shape-dependent block in cell proliferation correlated with a failure to increase cyclin D1 protein level and to down-regulate the cell cycle inhibitor p27. Y-27632 decreased type I collagen gene expression and accumulation in HSC culture media. CONCLUSIONS: Our findings indicate that p160ROCK-mediated actin stress fiber assembly is involved in the pathophysiology of hepatic fibrogenesis and suggest that inhibitors of the RhoA-ROCK pathway might be useful therapeutically in liver fibrogenesis.

Adipocytes↗

Immunological and virological predictors of outcome during interferon-alpha therapy of chronic hepatitis C.

Results from a multicentre, clinical trial of interferon-alpha2a (IFN-alpha2a) for the treatment of chronic hepatitis C are reported. Serum hepatitis C virus (HCV) RNA levels were monitored as follows: before, and 2 days after, the first administration of IFN-alpha2a; during and at the end of treatment; and 6 months after completion of therapy. Peripheral blood lymphocyte subpopulations were measured, by two-colour flow cytometry, before and 3 h after the first intramuscular (i.m.) administration of 9 mega units (MU) of IFN-alpha2a. Virological responders had a significantly lower pretreatment level of CD11+ CD8- lymphocytes. Biochemical responders had significantly lower pretreatment levels of CD11- CD8+, human leucocyte antigen (HLA) DR- CD4- and HLA DR- CD8+ populations, and a higher pretreatment HLA DR+ CD4- population. These pretreatment differences disappeared 3 h after the first i.m. administration of IFN-alpha2a. CD11- CD8+ and HLA DR+ CD8+ cell populations became significantly lower in virological responders 3 h after the first i. m. administration of IFN-alpha2a. HLA DR+ CD4+ cell populations were increased less in biochemical responders. Thus, T-lymphocyte subpopulations were different between responders and non-responders to IFN therapy and IFN-modulated host immunity. Multivariate analysis showed that the pretreatment CD11+ CD8- cell population was an independent predictive factor of response to therapy. On the other hand, patients whose serum HCV RNA cleared or decreased within the first 2 days of IFN-alpha2a therapy were more likely to achieve a virological response. This predictive factor, however, was not an independent factor by multivariate analysis. These results suggest that host immunity is an important factor in response to IFN therapy, and HCV clearance within the first 2 days is a good predictive factor of response.

Adult↗

Bronchiolitis obliterans organizing pneumonia (BOOP) in a case of smouldering adult T-cell leukaemia.

Although various respiratory diseases have been reported in human T lymphotropic virus type-1 (HTLV-1) carriers or patients with adult T-cell leukaemia (ATL), there appears to be no report of the development of bronchiolitis obliterans organizing pneumonia (BOOP) in ATL or HTLV-1-related disorders. We describe a 51-year-old male with smouldering ATL who developed BOOP during a long-term follow up. Bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed in the right lower lobe B6 with infiltrative shadows. As a result of flow cytometric analysis of peripheral lymphocytes and BAL lymphocytes, histological examination of the biopsied lung specimen, and the clinical course, we excluded the pulmonary infiltration of ATL cells and bacterial infection. Thus, he was diagnosed as having BOOP and successfully treated with corticosteroid therapy. This is probably the first report of BOOP developing in ATL. Bronchiolitis obliterans organizing pneumonia should be considered in the differential diagnosis of pulmonary complications in HTLV-1 carriers or ATL patients since BOOP can be successfully treated by corticosteroids.

Cryptogenic Organizing Pneumonia↗

Platelet-derived growth factor receptor tyrosine kinase inhibitor AG1295 attenuates rat hepatic stellate cell growth.

Enhanced activity of receptor tyrosine kinases such as the platelet-derived growth factor-receptorbeta (PDGF-Rbeta) has been implicated as a contributing factor in the development of hepatic fibrosis. In this study we have used tyrosine kinase inhibitors of the tyrphostin class (AG1295) to specifically block autophosphorylation of PDGF-Rbeta and proliferation of rat hepatic stellate cells. We also examined the effect of AG1295 on the PDGF-BB-induced activation of the 44 kd and 42 kd mitogen-activated protein (MAP) kinase isoforms (p44mapk/p42mapk). Rat hepatic stellate cells were treated with AG1295 (10 micromol/L) for 24 hours and stimulated with PDGF-BB for 5 minutes. AG1295 specifically inhibited autophosphorylation of PDGF-Rbeta and caused a 20% decrease in PDGF-BB-stimulated bromodeoxyuridine incorporation by rat hepatic stellate cells. Treatment of rat hepatic stellate cells with AG1295 resulted in an inhibition of the PDGF-BB-induced activation of MAP kinase isoforms. Quantification of the immunoprecipitated tyrosine-phosphorylated phosphatidylinositol 3-kinase, phospholipase C-gamma, and p21ras guanosine triphosphatase-activating protein by Western blotting revealed that AG1295 treatment effectively inhibits tyrosine phosphorylation of these kinases in hepatic stellate cells. Our findings demonstrate that AG1295 is a selective inhibitor of the tyrosine phosphorylation of PDGF-Rbeta and its downstream signaling pathway, and this compound could offer a strategy for the treatment of fibrotic liver diseases.

Animals↗

Interstitial flow through the internal elastic lamina affects shear stress on arterial smooth muscle cells.

Interstitial flow through the tunica media of an artery wall in the presence of the internal elastic lamina (IEL), which separates it from the subendothelial intima, has been studied numerically. A two-dimensional analysis applying the Brinkman model as the governing equation for the porous media flow field was performed. In the numerical simulation, the IEL was modeled as an impermeable barrier to water flux, except for the fenestral pores, which were uniformly distributed over the IEL. The tunica media was modeled as a heterogeneous medium composed of a periodic array of cylindrical smooth muscle cells (SMCs) embedded in a fiber matrix simulating the interstitial proteoglycan and collagen fibers. A series of calculations was conducted by varying the physical parameters describing the problem: the area fraction of the fenestral pore (0. 001-0.036), the diameter of the fenestral pore (0.4-4.0 microm), and the distance between the IEL and the nearest SMC (0.2-0.8 microm). The results indicate that the value of the average shear stress around the circumference of the SMC in the immediate vicinity of the fenestral pore could be as much as 100 times greater than that around an SMC in the fully developed interstitial flow region away from the IEL. These high shear stresses can affect SMC physiological function.

Arteries↗

Acute occlusion of an abdominal aortic aneurysm--case report and review of the literature.

Acute thrombosis of an abdominal aortic aneurysm (AAA) is a surgical emergency. Only 44 cases have been reported in the literature. The mechanism of the thrombosis has not been delineated. The proposed etiologies include propagation of thrombus from distal artery occlusion, cardiac thromboembolism, and dislodgment of a mural thrombus. Patients often present bilateral lower extremity ischemia, mimicking a saddle embolism. Systemic heparinization immediately after diagnosis and prompt surgical revascularization can reduce the mortality rate. The authors present a patient with sudden thrombosis of an AAA who was successfully treated with an axillobifemoral bypass graft. All published cases of thrombosed AAAs are analyzed.

Acute Disease↗

The replication capacity of intact mammalian nuclei in Xenopus egg extracts declines with quiescence, but the residual DNA synthesis is independent of Xenopus MCM proteins.

In eukaryotes, the initiation of DNA synthesis requires the assembly of a pre-replicative complex (pre-RC) at origins of replication. This involves the sequential binding of ORC (origin-recognition-complex), Cdc6 and MCM proteins, a process referred to as licensing. After origin firing, the Cdc6 and MCM proteins dissociate from the chromatin, and do not rebind until after the completion of mitosis, thereby restricting replication to a single round in each cell cycle. Although nuclei normally become licensed for replication as they enter G(1), the extent to which the license is retained when cells enter the quiescent state (G(0)) is controversial. Here we show that the replication capacity of nuclei from Swiss 3T3 cells, in Xenopus egg extracts, is not lost abruptly with the onset of quiescence, but instead declines gradually. The decline in replication capacity, which affects both the number of nuclei induced to replicate and their subsequent rate of DNA synthesis, is accompanied by a fall in the level of chromatin-bound MCM2. When quiescent nuclei are incubated in egg extracts, they do not bind further MCMs unless the nuclei are first permeabilized. The residual replication capacity of intact nuclei must therefore be dependent on the remaining endogenous MCMs. Although high levels of Cdk activity are known to block MCM binding, we show that the failure of intact nuclei in egg extracts to increase their bound MCMs is not due to their uptake and accumulation of Cdk complexes. Instead, the failure of binding must be due to exclusion of some other binding factor from the nucleus, or to the presence within nuclei of an inhibitor of binding other than Cdk activity. In contrast to the situation in Xenopus egg extracts, following serum stimulation of intact quiescent cells, the level of bound MCMs does increase before the cells reach S phase, without any disruption of the nuclear envelope.

3T3 Cells↗

Potentially distinctive features of sinonasal inverted papilloma on MR imaging.

OBJECTIVE: The objective of this study is to describe potentially distinctive MR features of sinonasal inverted papilloma and those of coexisting squamous cell carcinoma. CONCLUSION: A sinonasal mass with a convoluted cerebriform pattern on T2- or enhanced T1-weighted images suggests inverted papilloma as a histologic diagnosis. Necrosis in a mass with such an appearance strongly suggests coexistent carcinoma.

Adult↗

[MRI of anterior cruciate ligament autografts].

The purpose of this study was to assess the usefulness of MRI in the evaluation of autografts after anterior cruciate ligament reconstruction. The subjects were 110 patients with anterior cruciate ligament reconstruction using patellar tendon autografts who underwent clinical examination, MRI, and arthroscopy of the knee. T1- and T2-weighted MR images were obtained in sagittal plane. Clinical findings were categorized into three groups: normal, borderline, and abnormal. The MRI appearances of the autografts were categorized into three types: straight continuous band (type I), interrupted band (type II) and generalized increased intensity band (type III). The clinical findings and MRI findings were compared with arthroscopic findings. Ninety-six percent of the type I showed no autograft tear on arthroscopy. In comparison with the clinical findings, MRI was found to be well correlated with arthroscopic findings. In conclusion, if the clinical findings are normal, patients are to be followed-up without MRI and arthroscopy. However, if clinical findings are either borderline or abnormal, MRI should be performed prior to arthroscopy.

Adolescent↗

[Pulmonary Nocardia otitidiscaviarum infection in an immunocompetent host].

A rare case of pulmonary Nocardia otitidiscaviarum (N. otitidiscaviarum) was encountered in an immunocompetent host. A 74-year-old man was admitted to our hospital with a high fever and a productive cough. His chest radiograph and CT scan revealed infiltrative shadows in the right middle and lower lung fields. Although several antibiotics (third-generation cephalosporin, minocycline, imipenem) were administered, the fever and cough persisted, and C-reactive protein remained elevated. Repeated sputum cultures showed normal flora, so a transbronchial lung biopsy and bronchoalveolar lavage (BAL) were performed bronchoscopically at the right S5. The BAL fluid contained acid-fast, branching filamentous structures. The microorganism was identified as N. otitidiscaviarum by the Research Center for Pathogenic Fungi and Microbial Toxicoses (Chiba University). Trimethoprim-sulfamethoxazole was therefore administered, but the fever continued to rise daily, and C-reactive protein remained elevated. This isolated N. otitidiscaviarum showed resistance to multiple antimicrobial agents in vitro when examined by the disk diffusion method, and so, on the basis of the antibiogram, the patient was treated with clarithromycin (oral, 600 mg/day) plus amikacin (400 mg/day), which proved successful. Testing for pulmonary nocardiosis should be added to the differential diagnosis procedures for refractory pneumonia as an opportunistic infection and for community-acquired pneumonia.

Aged↗