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Biomedical subjects

T Fujisawa

Publications and source records attributed to T Fujisawa.

At least 91 records · Page 5Linked to original sources

Completely resected stage IIIA non-small cell lung cancer: the significance of primary tumor location and N2 station.

BACKGROUND: The number of N2 stations (single vs multiple N2 stations) is an important prognostic factor in patients with completely resected stage IIIA-N2 non-small cell lung cancer. However, the significance of both the N2 station(s) actually involved and the primary tumor location remains unclear. METHODS: The database was built with the use of a questionnaire survey on the survival of patients with pathologic stage IIIA-N2 non-small cell lung cancer completely resected between January 1992 and December 1993. The survey was performed by the Japan Clinical Oncology Group as of July 1999. The data include information on the survival and N2 stations of 402 patients. RESULTS: A frequently metastasized single N2 station was the lower pretracheal station in primary tumors in the right upper lobe, the subaortic station in the left upper lobe, and the subcarinal station in the right middle or lower lobe and the left lower lobe. In multiple N2 stations, the frequency of metastasis of the N2 station observed in a single N2 station was as high as 72% to 89%, and one or two other frequently metastasized stations were added to each group. Regarding the survival of patients with a primary tumor in each lobe except for the left lower lobe, a single N2 station resulted in a significantly better survival than did multiple N2 stations. Furthermore, the overall survivals classified according to each primary site showed a significant difference among the four primary sites (P =.04). CONCLUSIONS: The primary tumors in each lobe showed a prevalence of N2 station(s). The number of N2 stations is a good prognosticator except in patients with a primary tumor in the left lower lobe. In addition, the site of a primary tumor itself is also considered to influence the survival of the patients.

Adult↗

Colonization with Schizophyllum commune of localized honeycomb lung with mucus.

We report a surgical case involving localized honeycomb lung with mucus, caused by colonization of a Schizophyllum commune, which displayed a tumorous shadow in the right upper mediastinum. A 74-year-old male with a history of tuberculosis in the 1970s was referred to Chiba University Hospital (Chiba, Japan) with an abnormal shadow evident in the chest roentgenogram. A transbronchial biopsy failed to yield a definite diagnosis. We resected the right upper lobe, which was found to contain a consolidative lesion filled with viscous mucus in the right upper lobe adjacent to the right upper mediastinum. Microscopic examination revealed a honeycomb lung formation with mucus in the destroyed space. Culture of the mucus yielded a whitish filamentous fungus, positively identified as S. commune. This is the first report of S. commune leading to a deposit of mucus and the formation of a consolidative lesion in the destroyed lung.

Aged↗

Regulation of surface FcepsilonRI expression on human eosinophils by IL-4 and IgE.

BACKGROUND: Recent studies have demonstrated that eosinophils from allergic patients express low levels of FcepsilonRI on their surface, but the regulatory mechanisms of eosinophil surface FcepsilonRI expression are not fully understood. We investigated whether IL-4 and IgE, which are reported to regulate surface FcepsilonRI expression on human mast cells, are able to affect surface FcepsilonRI expression in normal human eosinophils. METHODS: Eosinophils purified from peripheral blood were cultured with IL-5 and with or without IL-4 and/or IgE, and surface FcepsilonRI expression was analyzed by flow cytometry using an anti-FcepsilonRI mAb, CRA-1. RESULTS: Apparent FcepsilonRI expression (approximately 1% of mast cell FcepsilonRI levels) was observed in eosinophils cultured with both IL-4 and IgE. A combination of IL-4 (>or=1 ng/ml) and IgE (>or= 0.5 microg/ml) was necessary for the maximal induction of surface FcepsilonRI expression. In the presence of IL-4 and IgE, eosinophils cultured for 2 days demonstrated low but statistically significant levels of surface FcepsilonRI, which reached a plateau after 7 days of culture. However, cross-linkage of surface FcepsilonRI molecules by CRA-1 or anti-IgE did not induce any eosinophil activation. CONCLUSIONS: IL-4 and IgE can affect the levels of surface FcepsilonRI on normal human eosinophils. FcepsilonRI expression on eosinophils may be regulated by a mechanism similar to that in mast cells.

Cells, Cultured↗

Regulation of chemokine receptor expression in eosinophils.

Signals via chemokine receptors play an important role in the accumulation of eosinophils at allergic inflammatory sites. Eosinophils constitutively express CC chemokine receptor 3 (CCR3) and, to a lesser extent, CCR1. CCR3 is mainly responsible for migration of resting eosinophils, and its specific ligand, eotaxin, represents the most potent chemoattractant for eosinophils. Some reports also suggest the expression of CXC chemokine receptor 1 (CXCR1) and/or CXCR2 in eosinophils. In addition, we recently reported the functional expression of CXCR4. The ligand of CXCR4, stromal cell-derived factor-1 (SDF-1), was able to induce a strong migratory response comparable to that by eotaxin. In contrast to the CCR3/eotaxin system which is mainly regulated at the level of ligand production, the CXCR4/SDF-1 system is regulated at the level of receptor expression. CXCR4 expression was completely attenuated by IL-4 and IL-5 and upregulated by IFN-gamma and dexamethasone, while CCR3 expression was only marginally affected. The balance between the biological effects of these chemokine systems may affect the distribution and migration of eosinophils.

Animals↗

Oral tolerance induction by type V collagen downregulates lung allograft rejection.

Immunization with specific proteins or peptides has been used to induce immunologic tolerance to allografts other than the lung. Recently, we have reported that the immune response to lung alloantigen also involves an immune response to type V collagen [col(V)]. The purpose of the current study was to determine if oral administration of col(V) to lung allograft recipients before transplantation downregulates acute rejection episodes. The data show that, compared with controls, col(V)-fed recipients had fewer polymorphonuclear cells and lymphocytes in allograft bronchoalveolar lavage fluid, and reduced rejection pathology. Data showing that col(V)- fed allograft recipients had diminished delayed-type hypersensitivity (DTH) responses to donor alloantigens suggest that feeding col(V) prevented allograft rejection by inducing tolerance to donor antigens. Systemic production of transforming growth factor (TGF)-beta, interleukin (IL)-4, or IL-10 has been reported to be a mechanism for oral tolerance-induced suppression of immune responses. Feeding col(V) induced upregulated production of TGF-beta, but not IL-4 or IL-10 in serum. Neutralizing TGF-beta recovered the DTH response to donor antigen in tolerant allograft recipients. Collectively, these data show that oral administration of col(V) is a novel approach to induce immunologic tolerance to lung allografts, and that TGF-beta contributed to suppression of the rejection response.

Adaptation, Physiological↗

Enhancement of foot formation in Hydra by a novel epitheliopeptide, Hym-323.

During the course of a systematic screening of peptide signaling molecules in Hydra magnipapillata, a novel peptide, Hym-323, which enhances foot regeneration was identified. The peptide is 16 amino acids long, and is encoded in the precursor protein as a single copy. Northern blot analysis, in situ hybridization analysis and immunohistochemistry showed that it was expressed in both ectodermal and endodermal epithelial cells throughout the body, except for the basal disk and the head region. The peptide enhanced foot regeneration by acting on epithelial cells. Lateral transplantation experiments indicated that the foot activation potential was increased in the peptide-treated tissue. These results suggest that Hym-323 is a peptide involved in a foot-patterning process in Hydra.

Amino Acid Sequence↗

Design and synthesis of carboxylate inhibitors for matrix metalloproteinases.

A series of carboxylate compounds were prepared from N(alpha)-substituted 2,3-diaminopropionic acid and were tested for efficacy as matrix metalloproteinase (MMP) inhibitors. During modeling of the initial compound 10a, we utilized three-dimensional structure modeling software (InsightII/Discover Ver. 2.98). Some of the prepared carboxylate derivatives, such as carbamate compounds (12c,d, 22) and sulfonamide compounds (14b,c), proved to be effective MMP-1 inhibitors (with IC50 values of a 10(-6) M order), depending on the substituent at the N(alpha)-position of 2,3-diaminopropionic acid. Some of them were also evaluated for inhibition of stromelysin-1 (MMP-3), and the sulfonamide compound 14c exceeded the lead compound 5b in its MMP-3 inhibitory potency. For the carbamate compounds, we investigated the minimum molecular size at which the MMP-1 inhibitory potency was maintained, and found that this was P3-P1' compound 10b.

Carboxylic Acids↗

Intraspecific divergence of Saccharomyces kluyveri as revealed by the nucleotide sequences of 18S-28S rRNA spacer regions and alpha-galactosidase MEL genes.

In the five strains classified as the yeast Saccharomyces kluyveri, several substitutions were observed in the two internal transcribed spacer regions between 18S and 28S rRNA. A PCR reaction with primers targeted to the MEL1 gene of Saccharomyces cerevisiae amplified fragments of the expected size, and those sequences showed significant divergence in the strains of S. kluyveri.

Blotting, Southern↗

Sequence analysis of candidate genes for common susceptibility to type 1 and type 2 diabetes in mice.

Although type 1 and type 2 diabetes are regarded as clinically distinct diseases, several lines of evidence have suggested common genetic factors between the two types of diabetes. The non-obese diabetic (NOD) mouse, an animal model of type 1 diabetes, and the Nagoya-Shibata-Yasuda (NSY) mouse, a model of type 2 diabetes, are derived from the same outbred colony, Jcl:HCR, suggesting a shared susceptibility between the two types of diabetes in mice. Genetic as well as functional studies have supported the possibility that Tcf2, which encodes the transcription factor, hepatocyte nuclear factor 1beta (HNF-1beta), is a candidate gene for the common susceptibility between NSY and NOD mice. Txn, encoding thioredoxin which is a redox (reduction/oxidation)-active protein, is also a positional and functional candidate for a common susceptibility gene. To investigate whether either of these two genes is a common susceptibility gene, the coding nucleotide sequences of these two genes were compared among the NSY, NOD and control C3H strains. The coding sequence of Tcf2 of the NOD mouse was identical to that of the C3H mouse, but was different from that of the NSY mouse. The coding sequence of Txn was identical in the three strains. These data suggest that neither of the two genes is a common susceptiblity gene between type 1 and type 2 diabetes in mice.

Animals↗

Urine-based enzyme-linked immunosorbent assay for the detection of Helicobacter pylori infection in children.

OBJECTIVE: Serology and (13)C-urea breath test have been widely used as noninvasive tests to detect Helicobacter pylori infection. However, easier collection of samples and lower costs are desirable for diagnosis of the individual patient or for use in epidemiologic studies. Our aim was to study the diagnostic accuracy of a recently developed urine-based enzyme-linked immunosorbent assay (ELISA) kit for the detection of H pylori-specific immunoglobulin G (IgG) antibodies in children. STUDY DESIGN: Specimens of serum and randomly voided urine were collected from 816 children (0-15 years old) and were analyzed using 2 serum-based ELISA kits and a urine-based ELISA kit, respectively. Based on results of serology, the sensitivity, specificity, and accuracy of the urine-based ELISA kit were evaluated. With regard to false-positive and false-negative results, urinary IgG concentrations and IgG/creatinine levels were studied. RESULTS: Both serum-based ELISAs were positive in 41 children and were negative in 666, who were enrolled in this study. The remaining 109 children were excluded because of disagreement between the results of the 2 serum-based ELISAs, including indeterminate values. Overall sensitivity, specificity, and accuracy of urine-based ELISA test compared with serology were 85.4%, 95.5%, and 94.9%, respectively. On positivity rates, the urine-based ELISA was closely coincident with the serum-based ELISA in each age group. There was no correlation between antibody levels detected by urine-based ELISA and each serum-based ELISA. Urinary IgG concentrations and IgG/creatinine levels were significantly higher in false-positives and were lower in false-negatives than in true-positives plus true-negatives for serology. Most of those with false-positive results had trace to moderate proteinuria. CONCLUSIONS: The urine-based ELISA is an alternative to serum-based ELISA for diagnosis of H pylori infection in children and should be suitable for large-scale epidemiologic studies concerning the organism. In children with proteinuria, results of the test should be interpreted with caution. It is possible that the urine-based ELISA method would be applicable to diagnosis of other infectious diseases.

Adolescent↗

Occurrence of clostridia in commercially available curry roux.

The occurrence of clostridia was investigated in a total of 60 commercially available curry roux samples. Clostridia were isolated from 37 (62%) samples, and Clostridium perfringens was isolated from 7 (12%) samples. The isolates of C. perfringens did not produce enterotoxin. The frequency of occurrence was higher by the enrichment broth culture detection method than by the agar plate or pouch method. These findings suggest that enrichment broth culture is necessary for the detection of clostridia.

Bacteriological Techniques↗

[Surgery for non-small cell lung cancer based on the T factor].

We review the indications of surgery in patients with non-small cell lung cancer (NSCLC) based on the T factor, focusing on peripheral small tumors, invasion to other organs, and the presence of malignant pleural effusion or intrapulmonary metastasis. While limited surgery in patients with peripheral, small-sized NSCLC preserves postoperative pulmonary function, the prospects for long-term survival are reduced due to the likelihood of recurrence, Novel prospective studies are being conducted to determine the indications for limited surgery in such patients which focus on histology, tumor size, and pulmonary function. In some patients with locally advanced disease, especially with invasion of the chest wall (T3), pericardium (T3), left atrium (T4), great vessel (T4), and carina (T4) and with malignant pleural effusion found intraoperatively and ipsilateral intrapulmonary metastasis, complete resection results in long-term survival. Thus surgery should be considered in patients without N2 disease.

Carcinoma, Non-Small-Cell Lung↗

Sequence analysis of hepatitis B virus genomes from an infant with acute severe hepatitis and a hepatitis B e antigen-positive carrier mother.

It is well known that fulminant hepatitis B can occur in infants born to hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) carrier mothers, whereas fulminant hepatitis and severe hepatitis are uncommon in infants born to HBeAg-positive mothers. We have encountered an infant with severe acute hepatitis B born to a HBeAg-positive mother. The aim of this study was to determine whether HBV variants contribute to the pathogenesis of fulminant hepatitis and severe hepatitis in an infant born to an HBeAg-positive mother. The nucleotide sequence of HBV genomes from the infant and his HBeAg-positive carrier mother was analyzed. All HBV isolated from the infant and his mother were subtype adr. The sequences of the cloned HBV genomes, each including a part of the X and precore/core regions, isolated from the infant were almost identical (homology of 99.1-99.9%) to those from his mother. There was no mutation in any of the 17 clones examined at nucleotides 1762 and 1764 in the core promoter, which is reported to be associated with fulminant hepatitis. A point mutation at nucleotide 1758 in the second AT-rich region of the basic core promoter was present in all clones. None of the clones had a point mutation at nucleotide 1896 of the precore region. In this study, no specific HBV variants contributing to the development of neonatal severe hepatitis were found. There is a possibility that host factors rather than viral factors play an important role in some cases of severe neonatal hepatitis B.

Adult↗

Lack of association between hepatocyte nuclear factor-1beta gene and common forms of type 2 diabetes in the Japanese population.

Mutations in the hepatocyte nuclear factor-1beta (HNF-1beta) gene have been shown to be a cause of maturity-onset diabetes of the young (MODY). We studied the contribution of the HNF-1beta gene to susceptibility to common forms of Type 2 diabetes in the genetically homogeneous Japanese population, by investigating the allelic association of Type 2 diabetes with two markers in the HNF-1beta region. The frequency of a nonsense mutation, R177X, which was previously reported in a Japanese family, was also studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using a mismatch primer. A total of 200 subjects were studied. There was no significant difference in allele frequencies of either of the two polymorphisms studied between patients with Type 2 diabetes and control subjects, or between subgroups of patients subdivided by the presence of mild or severe diabetic nephropathy. None of the subjects studied had R177X mutation, giving a frequency of less than 1.1% in common forms of Type 2 diabetes in Japan. These results suggest that mutations in the HNF-1beta gene derived from a limited number of founders are not a major cause of common forms of Type 2 diabetes, even in the genetically homogeneous Japanese population.

Adult↗

Identification of missense mutation (G365R) of the butyrylcholinesterase (BCHE) gene in a Japanese patient with familial cholinesterasemia.

A point mutation which caused a silent phenotype of human serum butyrylcholinesterase (BChE) was identified in the genomic DNA of a 57-year-old Japanese woman who visited our hospital because of pneumonia. The propositus exhibited an unusually low level of BChE activity, whereas her son and daughter had an intermediate level. Immunologically, there was an absence of BChE protein in the propositus's serum. DNA sequence analysis of the propositus demonstrated a point mutation at codon 365 (GGA-CGA), resulting in a Gly-Arg substitution. A family study showed her son and daughter to have the same mutation.

Butyrylcholinesterase↗

Time-resolved x-ray diffraction reveals multiple conformations in the M-N transition of the bacteriorhodopsin photocycle.

We measured the M-N transition of wild-type bacteriorhodopsin (pH 9, 10 degrees C) by time-resolved x-ray diffraction study at SPring8 BL45XU-A. We confirmed the accumulation of M and N intermediates by absorbance measurements, and we found that the time resolution of x-ray diffraction experiments (244 ms) was sufficient to resolve the M-N transition. From the x-ray diffraction data, three components were decomposed by singular value decomposition analysis. The existence of three components in the M-->N-->BR reaction revealed that BR changes its structure during the M-N transition. Moreover, the difference Fourier maps of reconstituted fast and slow decay components clearly showed that the electron density distributions of the F helix changes in the M-N transition. The observed structural change at the F helix will increase access of the Schiff base and D96 to the cytoplasmic surface and facilitate the proton transfer steps that begin with the decay of the M state.

Bacteriorhodopsins↗