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Biomedical subjects

H Yanagawa

Publications and source records attributed to H Yanagawa.

At least 55 records · Page 3Linked to original sources

Relationship between breast milk feeding and atopic dermatitis in children.

OBJECTIVE: To determine whether or not the breast milk feeding has a role in the prevalence of atopic dermatitis among children. METHODS: The target population of the study was all children participating in health check-up program for 3-year-old children in 60 municipalities locating 10 selected prefectures during designated 2 months between October and December 1997. Using a questionnaire, information on nutrition in infants (breast milk only, bottled milk only, or mixed), parity, mothers' age at birth, and a history of atopic dermatitis was obtained. Besides, data on potential confounding factors were obtained. RESULTS: Questionnaires from 3856 children (81.6% of those who were to participate in the programs, and 96.4% of children who participated them) were analyzed. After the adjustment for all potential confounding factors using unconditional logistic models, the risk of atopic dermatitis was slightly higher among children with breast milk (odds ratio [OR] = 1.16 with 95% confidence interval [CI] 0.96-1.40). Mothers' age at birth (OR for those who were more than 30 years or older in comparison with those who were younger than 30 years = 1.15; 95% CI, 0.96-1.37) and those with second or later parity orders (OR = 1.14, 95% CI; 0.95-1.35) showed odds ratios that were higher than unity without statistical significance. CONCLUSION: Breast milk elevates the risk of atopic dermatitis slightly without statistical significance; the risk may be, however, higher in children in second or later parity orders.

Adult↗

Human interferon-gamma enhances expression of ganglioside GM2 on human lung cancer cells and their susceptibility for antiganglioside GM2 monoclonal antibody-dependent cellular cytotoxicity.

Interferons are known to modulate several cellular functions by the induction of various proteins. In this study, we demonstrated that human interferon-gamma (HuIFN-gamma) enhanced the expression of ganglioside GM2 (GM2), which is a kind of tumor-associated antigen substantially expressed in human lung cancer and that human lung cancer cells expressing GM2 became more susceptible to anti-GM2 monoclonal antibody (mAb)-dependent tumor cell killing mediated by human effector cells after HuIFN-gamma treatment. GM2 expression on human lung cancer cells treated with or without HuIFN-gamma was measured by flow cytometry. The antibody-dependent cellular cytotoxicity (ADCC) activity was assessed by 4-h 51Cr release assay. HuIFN-gamma enhanced GM2 expression on human small-cell lung cancer (SCLC), SBC-3, and human non-small-cell lung cancer (NSCLC), A549 cells in a dose-dependent manner. The optimal concentration of HulIFN-gamma was 1,000 U/ml. The effect of HulFN-gamma reached maximum after 4 days of culture. HulFN-gamma did not have any effect to enhance the expression of other gangliosides in SBC-3 cells. No other cytokines used in this study modulated GM2 expression in SBC-3 cells. Anti-GM2 mAb-dependent ADCC activities induced by lymphocytes and monocytes were more potent against IFN-gamma-treated SBC-3 and A549 cells than nontreated cells. Taken together, HulFN-gamma combined with anti-GM2 mAb may be useful for immunotherapy against GM2-positive human lung cancer.

Antibodies, Monoclonal↗

[Case-control study of risk factors for cedar pollinosis among parents of 3-year-old children].

PURPOSE: To identify risk factors associated with cedar pollinosis among parents of three-year-old children. METHODS: The subjects were parents whose children underwent health examination at the age of three years in September and October 1997 in Tochigi prefecture. We distributed questionnaires to the examinees beforehand with the request that they be filled in and brought to the examination site. Information on parents' environmental factors (place of residence, type and structure of housing, and distance from roads with heavy traffic), and mothers' past history and family history of allergic diseases was obtained. We defined cedar pollinosis in terms of three symptoms, sneezing, nasal discharge, and nasal obstruction, between February and May. Controls were those who did not have any of the three symptoms. Environmental factors were assessed with univariate and multivariate analyses using unconditional logistic models. Maternal genetic factors were also analyzed with odds ratios and 95% confidence intervals calculated for each. We also compared odds ratios of environmental factors between groups with and without genetic factors. RESULTS: Of the parents of children taking the health examination, 90.2% took part (2,968 of 3,291 couples). Information was obtained from 2,846 mothers and 2,905 fathers. Mother and father cases were 312 and 229, and controls were 1,857 and 1,934, respectively. For the univariate analysis of environmental factors, place of residence (residential area/agricultural area), type of housing (apartment complex/solitary house), structure (reinforced concrete building/wooden house), and distance from heavy traffic (< 100 m/100 m+) were positively related to cedar pollinosis. For the multivariate analysis using unconditional logistic models, the odds ratio was significantly high for distance from heavy traffic (< 100 m/100 m+) among fathers. Mothers' past history and family history of allergic diseases showed high odds ratios for cedar pollinosis. We classified groups with and without past and family histories of allergic diseases (group with and without genetic factors) for assessment with multivariate analyses. Odds ratios for the group with an allergic history were higher than for those without such a history, but difference for factors such as, distance from heavy traffic type of housing, and structure were not statistically significant. CONCLUSION: Risk of cedar pollinosis increases with distance from heavy traffic among fathers. Mothers with histories of allergy show slightly elevated odds ratios for environmental factors, but without statistic significance.

Case-Control Studies↗

[Validity of the infectious disease surveillance system on comparison of nationwide surveys of Kawasaki disease during a 10 year period].

PURPOSE: To verify the validity of the infectious disease surveillance system in Japan using data for Kawasaki disease. MATERIALS AND METHODS: Data from nationwide surveys of Kawasaki disease conducted by the Kawasaki Disease Research Committee every two years over the 10 years (120 months) from 1989 through 1998 were used to calculate a gold standard. Then, the monthly numbers of patients with Kawasaki disease reported by monitoring hospitals (about 550 hospitals) to the surveillance system were compared with this gold standard. Each of the monthly numbers was standardized by division by the average monthly number of patients over the 120 months. Observations for 3 districts (eastern part, central part, and western part of Japan) were conducted as well as for the whole country. RESULTS: The number of patients reported to the surveillance system varied more widely than in the nationwide survey, but directions of the fluctuations were similar to the chronologic changes in nationwide numbers. Accordingly, a high correlation coefficient value of 0.794 was obtained (p < 0.01). Similar results were observed in all 3 districts. The correlation coefficients were 0.709 for the eastern part, 0.561 for the central part, and 0.712 for the western part, respectively, and all of them were of statistically significant. CONCLUSION: Changes in number of patients with Kawasaki disease reported to the surveillance system resemble the pattern of the gold standard.

Communicable Diseases↗

Fluorescence labeling of the C-terminus of proteins with a puromycin analogue in cell-free translation systems.

We have developed a new method for the C-terminus-specific fluorescence labeling of proteins. This method is based on the experimental finding that a fluorescent puromycin analogue at lower concentrations bonds efficiently to the C-terminus of mature proteins in cell-free translation systems using mRNA without a stop codon. This labeling is performed under moderate conditions and its labeling efficiency is in the range of 50-95%. Here we demonstrate a protein-protein interaction assay using fluorescence polarization measurement. This labeling method should also be useful for other rapid molecular interaction assays without purification of the labeled proteins, such as fluorescence correlation spectroscopy.

Cell-Free System↗

Massive outbreak of Escherichia coli O157:H7 infection in schoolchildren in Sakai City, Japan, associated with consumption of white radish sprouts.

In July 1996, an outbreak of Escherichia coli O157:H7 infection occurred among schoolchildren in Sakai City, Osaka, Japan. This outbreak developed in 13 North-East District and 34 Middle-South District elementary schools in the city. All children hospitalized on July 17-19 had presented on July 8 (North-East District) and July 9 (Middle-South District). School lunches served on July 1 and 8 in the North-East District and on July 1, 4, 8, and 9 in the Middle-South District were proposed by a food consumption study to be associated with infection. White radish sprouts from a single farm were the only uncooked food common to the most highly implicated meals on the involved days in two school districts (sweet and sour chicken with lettuce on July 8 in the North-East District and chilled Japanese noodles on July 9 in the Middle-South District). Two incidents of E. coli O157:H7 in neighboring areas were also related to white radish sprouts from the farm. The pulse-field gel electrophoresis patterns of isolates from patients in these two districts and the neighboring areas were identical. Thus, it was concluded that the cause of the outbreak was the white radish sprouts shipped on July 7-9 from one particular farm.

Child↗

STABLE: protein-DNA fusion system for screening of combinatorial protein libraries in vitro.

We have developed a new method that permits the complete in vitro construction and selection of peptide or protein libraries. This method relies on an in vitro transcription/translation reaction compartmentalized in water in oil emulsions. In each emulsion compartment, streptavidin (STA)-fused polypeptides are synthesized and attached to the encoding DNA via its biotin label. The resulting protein-DNA fusion molecules recovered from the emulsion can be subjected to affinity selection based on the properties of the peptide portion, whose sequence can be determined from that of its DNA-tag. This method, named 'STABLE' (STA-biotin linkage in emulsions), should be useful for rapid in vitro evolution of proteins and for ligand-based selection of cDNA libraries.

Bacterial Proteins↗

Insertional gene fusion technology.

The classical 'end to end' gene fusion technique has widely been used for monitoring gene expression, biological screening and purification of recombinant proteins. Recent progress with the 'insertional' gene fusion approach, on the other hand, has demonstrated that this technique can be utilized for membrane protein topology analysis, display of randomized protein libraries and design of biosensor proteins. In this review, we describe examples of insertional gene fusion and compare the old and new gene fusion techniques.

Artificial Gene Fusion↗

Relative risk of Creutzfeldt-Jakob disease with cadaveric dura transplantation in Japan.

By May 1996, 43 cases of Creutzfeldt-Jakob disease with cadaveric dura transplantation were reported during a nationwide survey in Japan. With the assumption that the number of patients receiving the transplantation each year was 20,000, the incidence of the disease among patients receiving cadaveric dura grafts was compared with the annual incidence in the general population. Cumulative incidence was between 0.017 and 0.048%. The estimated relative maximum risk was 104.9, and even the minimum relative risk was as high as 29.2.

Cadaver↗

Design of generic biosensors based on green fluorescent proteins with allosteric sites by directed evolution.

Protein-engineering techniques have been adapted for the molecular design of biosensors that combine a molecular-recognition site with a signal-transduction function. The optical signal-transduction mechanism of green fluorescent protein (GFP) is most attractive, but hard to combine with a ligand-binding site. Here we describe a general method of creating entirely new molecular-recognition sites on GFPs. At the first step, a protein domain containing a desired molecular-binding site is inserted into a surface loop of GFP. Next, the insertional fusion protein is randomly mutated, and new allosteric proteins that undergo changes in fluorescence upon binding of target molecules are selected from the random library. We have tested this methodology by using TEM1 beta-lactamase and its inhibitory protein as our model protein-ligand system. 'Allosteric GFP biosensors' constructed by this method may be used in a wide range of applications including biochemistry and cell biology.

Allosteric Regulation↗

Permutation of modules or secondary structure units creates proteins with basal enzymatic properties.

The RNase activity of barnase mutants obtained by the permutation of modules or secondary structure units was investigated. Four of the 45 mutants had weak but distinct RNase activity, and they had unique optimum pHs and temperatures like natural enzymes. One of the active mutants had an ordered conformation, but the others did not. An active mutant having disordered conformation formed an ordered conformation in the presence of GMP, which is an inhibitor of this mutant. These results indicate that the amino acid sequences derived from barnase have sufficient plasticity to be rearranged into different proteins with basal enzymatic properties.

Bacterial Proteins↗

Foldability of barnase mutants obtained by permutation of modules or secondary structure units.

Modules, defined as stable, compact structure units in a globular protein, are good candidates for the construction of novel foldable proteins by permutation. Here we decomposed barnase into six modules (M1-M6) and constructed 23 barnase mutants containing permutations of the internal four (M2-M5) out of six modules. Globular proteins can also be subdivided into secondary structure units based on the extended structures that control the mutual relationships of the modules. We also decomposed barnase into six secondary structure units (S1-S6) and constructed 21 barnase mutants containing permutations of the internal four (S2-S5) out of six secondary structure units. Foldability of these two types of mutants was assessed by means of circular dichroism, fluorescence, and 1H-NMR measurements. A total of 15 of 23 module mutants and 15 of 21 secondary structure unit mutants formed definite secondary structures, such as alpha-helix and beta-sheet, at 20 microM owing to intermolecular interactions, but most of them converted to random coil structures at a lower concentration (1 microM). Of the 44 mutants, only two, M3245 and S2543, gave distinct near-UV CD spectra. S2543 especially showed definite signal dispersion in the amide and methyl regions of the 1H-NMR spectrum, though M3245 did not. Furthermore, urea-induced unfolding of S2543 monitored by far-UV CD and fluorescence measurements showed a distinct cooperative transition. These results strongly suggest that S2543 takes partially folded conformations in aqueous solution. Our results also suggest that building blocks such as secondary structure units capable of taking different stable conformations by adapting themselves to the surrounding environment, rather than building blocks such as modules having a specified stable conformation, are required for the formation of foldable proteins. Therefore, the use of secondary structure units for the construction of novel globular proteins is likely to be an effective approach.

Amino Acid Sequence↗

Presence and potent immunosuppressive role of interleukin-10 in malignant pleural effusion due to lung cancer.

The presence and possible role of interleukin (IL)-10 were examined in malignant pleural effusion due to lung cancer. In 37 out of 55 cases examined, IL-10 was detectable in pleural effusion and the mean level with standard error was 62.1+/-12.1 pg/ ml. Spontaneous and lipopolysaccharide-induced production of anti-tumor cytokines such as IL-1beta and tumor necrosis factor (TNF)-alpha, by pleural macrophages, obtained from five patients with malignant pleurisy, were suppressed by IL-10. These findings suggest that IL-10 is present in the tumor-growing site and acts as a suppressive factor of local anti-tumor immunity in humans.

Aged↗

Cytolysis of human dendritic cells by autologous lymphokine-activated killer cells: participation of both T cells and NK cells in the killing.

Dendritic cells (DC) play a key role in the initiation of immune response by stimulating the naive T cells. The fate of DC after the initiation of immune response is not clearly understood. Although there are few reports implicating natural killer (NK) cells in the elimination of DC, killing of DC by LAK cells, and specifically by T cells, has not been studied. In this study, we observed that DC, generated from monocytes, in vitro in the presence of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), and tumor necrosis factor alpha were susceptible to cytolysis by lymphokine-activated killer (LAK) cells induced in the presence of IL-2 and IL-15 but not IL-12 alone. However, LAK cells induced by a combination of IL-12 and suboptimal dose of IL-2 were cytotoxic to DC. When purified lymphocytes were activated with IL-2, the CD8+/CD57- fraction (T-LAK), but not the CD8-/CD57+ fraction (NK-LAK) was cytotoxic to autologous DC. However, when unseparated peripheral blood mononuclear cells were used to generate LAK cells, both T-LAK and NK-LAK fractions showed equal cytotoxicity against autologous DC. Monoclonal antibodies against CD54, CD11a, and CD18 significantly inhibited the cytolysis, indicating that the killing involves the engagement of CD54 with its ligands.

Antibodies, Blocking↗

A case of resectable lung adenocarcinoma associated with sarcoidosis.

A 71-year-old woman with uveitis was referred to our hospital for further examination of the possible underlying diseases. In roentgenological examination with plain X-ray and CT scan, hilar and mediastinal lymphadenopathy and a mass shadow in the right upper lung field was observed, whereas fibrotic changes were not obvious in both lung fields. Transbronchial lung biopsy with fiberoptic bronchoscope revealed granulomatous interstitial pneumonia. CD4-positive lymphocytes were increased in bronchoalveolar lavage. The patient was diagnosed as having sarcoidosis. Subsequently, right upper lobectomy was performed, and Stage I lung adenocarcinoma was diagnosed. The patient is under follow up without medication and the disease has been stable for two years. A relationship between epithelioid granulomatosis and malignant diseases is discussed and a review of the literature is given. Since it is still controversial as to the incidence of malignant diseases in sarcoidosis patients, it is important to accumulate data on these associations.

Adenocarcinoma↗

Vascular endothelial growth factor in malignant pleural effusion associated with lung cancer.

The presence of vascular endothelial growth factor (VEGF) was examined by enzyme immunoassay in 60 cytology-documented malignant pleural effusions associated with primary lung cancer and 51 other benign and malignant pleural effusions. Exudative pleural effusions contained significantly higher amounts of VEGF than transudative pleural effusions. Among exudative pleural effusions, levels of VEGF in malignant pleural effusions associated with lung cancer were significantly higher than those of benign exudative pleural effusions. There was no significant difference in pleural VEGF in patients with different histological types or clinical stages of lung cancer. Serial measurement of pleural VEGF levels was performed in six lung cancer patients treated with intrapleural instillation of recombinant interferon gamma, and reduction of pleural effusion was associated with decreasing pleural VEGF levels. These findings suggest that VEGF has a role in the accumulation of exudative pleural effusions, especially that of malignant pleural effusion associated with lung cancer.

Adenocarcinoma↗

Factors related to cardiac sequelae of Kawasaki disease.

Among the 35.210 patients with Kawasaki disease who were reported in nationwide surveys from 1991 to 1996, 83% were treated with gamma-globulin (GG). Those treated with a total dose of 1000 mg/kg (9098 patients) and 2000 mg/kg (7012 patients) were selected as the subjects of the study on the relationship between the development of cardiac sequelae, in particular of giant aneurysms, and related factors using logistic regression models. Among the two groups that received 1000 mg/kg and 2000 mg/kg, respectively, the odds ratios for cardiac sequelae were significantly high for males, those < 6 months and > or = 7 years of age, and typical or recurrent cases. Except for those < 6 months of age, the odds ratios of all the factors mentioned above were higher for the incidence of giant coronary aneurysms than those for cardiac sequelae. The preventive effects of GG therapy for cardiac sequelae and in particular giant aneurysms, were significantly low when GG administration was initiated on day 8 or later after onset. In the group treated with 1000 mg/kg, the preventive effect was low when GG administration was spread over 3 days or longer. To prevent the development of cardiac sequelae, in particular giant coronary aneurysms, gamma-globulin therapy should be started as soon as possible and be completed within 2 days.

Child↗

Production of interleukin-10 by alveolar macrophages from lung cancer patients.

Interleukin (IL)-10 is known to be an autoregulatory factor of functions of monocyte macrophages. The purpose of this study was to determine whether IL-10 production by alveolar macrophages (AMs) is altered in patients with lung cancer. AMs were obtained by bronchoalveolar lavage from 25 patients with lung cancer and 14 control patients. The production of IL-10 by AMs was quantitated by enzyme immunoassay with or without stimulation with lipopolysaccharide (LPS). No significant difference in spontaneous and LPS-stimulated IL-10 production by AMs was observed between lung cancer patients and control patients (mean +/- SEM; 288.0 +/- 56.7 vs. 249.6 +/- 58.4 pg ml-1). IL-10 production of LPS-stimulated AMs was not impaired even in lung cancer patients with systemic metastasis. IL-4 failed to suppress LPS-induced production of IL-10 by AMs both in control patients and in lung cancer patients. In eight patients with lung cancer, IL-10 production by AMs was estimated before and after systemic chemotherapy and IL-10 production by LPS-stimulated AMs tended to increase after systemic chemotherapy from 152.3 +/- 51.9 to 278.0 +/- 112.8 pg ml-1. As IL-10 is a potent inhibitor of tumour angiogenesis, an important process of tumour progression, these results suggest that, even in advanced cancer patients, macrophages can produce potent angiogenesis inhibitor and systemic chemotherapy may augment this inhibitory activity in the lung.

Adult↗