A new polymorphism in the 5' flanking region of the human interleukin (IL)-4 gene.
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Alleles↗
Biomedical subjects
E Yamaguchi
Publications and source records attributed to E Yamaguchi.
Higher frequencies of numerical aberrations of chromosome 17 in primary gastric cancers are associated with lymph node metastasis.
We investigated the correlation between the frequency of numerical aberrations of chromosome 17 and clinicopathological features of gastric cancer. The copy number of chromosome 17 was examined with fluorescence in-situ hybridization (FISH) in frozen specimens from 100 primary gastric cancers. Chromosomal numerical aberrations were diagnosed as chromosomal loss (single signal) or gain (triple or more signals), in each cell. The frequency of numerical aberrations of chromosome 17 correlated significantly with the depth of invasion (P < 0.01), lymph node metastasis (P < 0.0001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.01). Numerical aberrations of chromosome 17 were associated with lymph node metastasis in 32 early gastric cancers. Multiple regression analysis identified the depth of invasion and numerical aberrations of chromosome 17 as independent significant determinants of lymph node metastasis. Our findings suggest that alterations in chromosome 17 may be linked with tumor progression in primary gastric cancer. Our results also indicate that numerical aberrations of chromosome 17 detected by FISH provide important information about the malignant potential (in particular, lymph node metastasis) of primary gastric cancer.
Adult↗
The angiotensin-converting enzyme DD gene is associated with poor prognosis in Finnish sarcoidosis patients.
Angiotensin-converting enzyme (ACE) genotypes may reflect prognosis in sarcoidosis. They were determined in 59 Finnish sarcoidosis patients and 70 healthy control subjects. The prognosis of the sarcoidosis patients was determined after follow-up for 1, 2, 3, 5 and >5 yrs and classified as good (normal chest radiograph and lung function, no signs of extrapulmonary disease activity within 2 yrs from diagnosis), intermediate (neither good nor poor) or poor (persisting unstable pulmonary infiltrates, vital capacity and diffusing capacity of the lung for carbon monoxide <50% predicted and/or extrapulmonary disease activity after >5 yrs follow-up). The DD, ID and II genotypes were found in 31 and 27%, in 54 and 49%, and in 15 and 24% of patients and control subjects respectively. The odds ratio (DD+ID to II) was 1.45 (95% confidence interval 0.60-3.49). The D alelle was found more often in patients (58%) and in control subjects (51%) than the I allele but the difference was not statistically significant. Statistically significantly more patients with the DD genotype had a poor prognosis compared with patients with II homozygotes and ID heterozygotes. Among 11 patients with Löfgren's syndrome (bilateral hilar lymphadenopathy and erythema nodosum), four had the DD genotype. Three of these patients had a prognosis despite presenting a clinical picture usually associated with a good prognosis. The angiotensin-converting enzyme genotype may be a prognostic marker in sarcoidosis and larger studies are warranted to define its clinical utility.
Case-Control Studies↗
Reduced expression of the alphabeta T-cell antigen receptor by alveolar T-cells.
A previous study revealed that reduced expression (modulation) of the CD3 antigen is a common characteristic of alveolar T-cells in health and disease. As CD3 molecules are noncovalently bound to T-cell antigen receptors (TCR), it was hypothesized that modulation of TCR was also a feature of alveolar T-cells. To demonstrate this, lymphocytes from bronchoalveolar lavage fluid were stained with an anti-alphabeta TCR antibody and analysed by flow cytometry. The expression of alphabeta TCR by alveolar T-cells was evaluated by calculating mean fluorescence intensity (MFI) and was compared with alphabeta TCR expression by autologous blood T-cells. As anticipated from a previous study, modulation of TCR was observed not only in healthy volunteers but also in patients with pulmonary sarcoidosis, other pulmonary diseases, and nonpulmonary diseases. There were no significant differences in MFI of alveolar T-cells among the study groups. The degree of modulation assessed by the difference of MFI between blood and alveolar T-cells was greater for CD4+ cells than for CD8+ cells owing to the higher MFI of CD4+ blood T-cells. Coculture of alveolar macrophages with blood T-cells in vitro induced partial modulation of TCR. These results demonstrate the ubiquity of modulation of T-cell receptors on alveolar T-cells and suggest, in contrast to a previous report by other investigators that it is caused by some nonantigenic mechanism possibly inherent in the alveolar milieu. The implications of this phenomenon in in vivo immune responses of the lung need to be examined.
Adult↗
Expression of adhesion molecules in hepatic metastases of colorectal carcinoma: relationship to primary tumours and prognosis after hepatic resection.
BACKGROUND: Adhesion molecules are closely involved in the development and growth of metastatic tumours. METHODS: We examined the expression of two adhesion molecules in liver metastatic tumours originating from colorectal carcinomas and correlated the expression of E-cadherin (EC) and CD44 variant exon 6 (v6) in these tumours with prognosis after hepatic resection. We examined 39 primary colorectal and 44 liver metastatic tumours obtained from 39 patients and 30 non-metastatic colorectal carcinomas as controls. The expression of EC in primary colorectal carcinomas of the metastasis group was significantly lower than in the non-metastasis group (P < 0.05). The expression of EC was low in metastatic liver tumours. RESULTS: The expression of CD44v6 in primary colorectal carcinomas of the metastasis group was significantly higher than in the non-metastasis group (P < 0.01). Expression of CD44v6 was high in metastatic liver tumours. However, there was no correlation between the expression of EC and CD44v6 or between each of these molecules and clinicopathological features of primary and metastatic tumours. Negative expression of EC and CD44v6 was a poor prognostic factor for survival after hepatic resection. CONCLUSIONS: Our results indicate that the lack of expression of EC and CD44v6 in liver metastases of colorectal cancer is associated with poor survival after surgery.
Aged↗
Differentiation of human single-positive fetal thymocytes in vitro into IL-4- and/or IFN-gamma-producing CD4+ and CD8+ T cells.
In this study we have investigated the capacity of human fetal thymocytes to differentiate in vitro into subsets of T cells with polarized Th1 or Th2 cytokine profiles. Stimulation of freshly isolated human fetal thymocytes with anti-CD3 mAb, cross-linked onto CD32,CD58,CD80-expressing mouse fibroblasts and subsequent culture in the presence of exogenous rIL-2 for 6 days, induced the production of both IL-4 and IFN-gamma, which was mainly produced by CD4+ single-positive (SP) and CD8+ SP cells respectively. Addition of rIL-4 during priming augmented IL-4 production in cultures of human fetal thymocytes, which was mainly due to an increased production of IL-4 by CD8SP cells. In contrast, addition of IL-4 to the cultures only slightly enhanced IL-4 production and had little effect on frequencies of IL-4-producing CD4SP cells. Both CD4SP and CD8SP cells produced IL-5, IL-10 and IL-13 at comparable levels, following priming in the presence of rIL-4. Priming in the presence of rIL-12 strongly enhanced the production of IFN-gamma in both CD4SP and CD8SP cells. No correlation between expression of CD27, CD30 and CD60, and a particular cytokine profile of differentiated thymocytes could be demonstrated. Together, these results demonstrate the full capacity of fetal human thymocytes to differentiate into cytokine-producing T cells in a priming milieu with appropriate stimulatory molecules and exogenous cytokines. In addition, CD4SP thymocytes rapidly differentiate into polarized Th2 cells following stimulation in vitro in the absence of exogenous rIL-4.
Animals↗
Natural killer cell subpopulations and cytotoxicity for infertile patients undergoing in vitro fertilization.
PROBLEM: We evaluated the participation of the lymphocyte subpopulations in the endometrium and peripheral blood on in vitro fertilization and embryo transfer (IVF-ET) outcomes. METHOD OF STUDY: Peripheral blood samples were analyzed for the expression of CD3, CD4, CD8, CD16, and CD56, using a FACScan, and for natural killer (NK) cell cytotoxicity, using a 51Cr assay. Endometrial samples obtained at a previous phase of the IVF cycle were analyzed for the expression of CD16 and CD56, using a FACScan. RESULTS: The percentages of CD56+ cells and CD16+CD56+ cells in the peripheral blood on the day of ET were significantly higher in the failed group than in the implanted group. In the endometrial tissue, the increase of the percentage of CD16+CD56dim cells and the decrease of the percentage of CD16-CD56bright cells in the aborted group were significant when compared with the those of the delivered group. CONCLUSIONS: The increase of cytotoxic NK cells in the peripheral blood and the endometrium may affect the therapeutic results of IVF-ET. It was suggested that modifications of NK cytotoxicity or of NK subpopulations might contribute to the improvements of IVF outcomes.
Adult↗
The role of the C-C chemokine receptor 2 gene polymorphism V64I (CCR2-64I) in sarcoidosis in a Japanese population.
A number of chemokines are produced by alveolar cells in the course of inflammatory reactions of sarcoidosis. C-C chemokine receptor 2 (CCR2) is a prominent receptor for the monocyte chemoattractant protein (MCP) group of C-C chemokines. A transition causing a valine to isoleucine substitution in transmembrane domain I of the CCR2 gene (CCR2-64I) that has a protective effect against the progression of human immunodeficiency virus-1 (HIV-1) disease has been described. To elucidate the role of this CCR2 polymorphism in sarcoidosis, we investigated the distribution of the CCR2-64I in 100 subjects with sarcoidosis (40.2 +/- 18.6 yr [mean +/- SD], 37:63 [male:female]) and 122 healthy control subjects (44.4 +/- 14.1 yr, 75:47). The distribution of the CCR2-64I allele was significantly different between subjects with sarcoidosis and healthy control subjects (p < 0.001). The presence of the CCR2-64I allele conferred a lower risk for the development of sarcoidosis (adjusted odds ratio = 0.369, 95% CI = 0.203 to 0.673). Our study suggests that this polymorphism may play a role in the pathogenesis of sarcoidosis, and further studies are needed to define the role of CCR2-64I.
Adolescent↗
[Pulmonary nocardiosis associated with Cushing's syndrome].
A 54-year-old man was admitted for further investigation of multiple nodules disclosed by a chest roentgenogram. Adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome was diagnosed because serum ACTH and serum cortisol levels were elevated with a loss of diurnal rhythm. Because several extensive examinations, including inferior petrosal sinus sampling, did not detest ACTH-producing tumors, the patient was also given a diagnosis of occult ectopic ACTH syndrome. The nodules disclosed on chest roentgenograms increased gradually in size and number, and some were cavitary. Bronchial secretion samples obtained by fiberoptic bronchoscopy contained numerous Nocardia asteroides bacteria. After treatment with sulfamethoxazole-trimethoprim, the nodules gradually disappeared, leaving only scars. Although mitotane had been continuously administered to inhibit the synthesis of intrinsic corticosteroids, pulmonary nocardiosis relapsed in the patient following the termination of sulfamethoxazole-trimethoprim therapy.
ACTH Syndrome, Ectopic↗
[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1997). II. Background of patients].
Clinical background was investigated on patients with urinary tract infections (UTIs) from whom 603 bacterial strains were isolated in 9 hospitals during the period from June, 1997 through May, 1998. 1. Distribution of age and sex of patients and type of infections Among males, those with ages less than 50 years were only 12.5%, and those in the 70's were most frequent (33.3%). Among females, those with ages less than 20 years were only 3.4%, and those in the 60's were the most frequent (22.9%). With regard to type of infections, more than a half of infections among males with ages 50 years or older were of complicated types, but most of infections among females were of uncomplicated types, especially those of ages less than 50 years. 2. Ages of patients and types of pathogens Escherichia coli was the most frequently isolated in uncomplicated and complicated UTIs without indwelling catheters. In complicated UTIs with indwelling catheters, Pseudomonas aeruginosa and Enterococcus faecalis had mainly detected, they had no relationship with ages. 3. Effect of antibiotic use on isolation frequencies of pathogens Use of antibiotics decreased pathogens isolated from patients with uncomplicated UTIs drastically (183 isolates before antibiotics compared to 13 after). Even isolated pathogens from patients with complicated UTIs decreased drastically with the use of antibiotics when indwelling catheters were not in use (175 isolates before antibiotics compared to 53 after), but when indwelling catheters were in use, antibiotics slightly decreased (109 isolates before antibiotics compared to 70 after). 4. Surgical procedures and types of causative organisms for UTIs E. faecalis were more isolated when a surgical procedures were used, and E. coli were more isolated when, they were not used in uncomplicated and complicated UTIs without indwelling catheters. In complicated UTIs with indwelling catheters, E. coli and E. faecalis were more isolated when a surgical procedures were used, and P. aeruginosa and Staphylococcus aureus were more isolated when they were not used.
Adult↗
Identification of two alpha-subunit species of GTP-binding proteins, Galpha15 and Galphaq, expressed in rat taste buds.
We cloned cDNAs for two G protein alpha-subunits belonging to the Galphaq family, each capable of activating PLCbeta, from rat tongue. One is a Galphaq in the narrow sense, and the other, termed rat Galpha15, is a rat counterpart of mouse Galpha15, sharing an amino acid sequence similarity of 94%. RT-PCR and Northern blot analysis demonstrated that rat Galpha15 and Galphaq were distinctly expressed in tongue epithelia containing taste buds. Immunostaining also showed that rat Galpha15, together with the Galphaq, was localized mainly in taste buds. These studies suggest the possibility that these two Galpha proteins function for taste signal transduction in sensory cells.
Amino Acid Sequence↗
Physiologic stress responses to laparoscopic cholecystectomy. A comparison of the gasless and pneumoperitoneal procedures.
BACKGROUND: Differences in the physiological stress response to pneumoperitoneal (PP) and gasless abdominal wall-lifting (AWL) procedures used for laparoscopic cholecystectomy have not been properly evaluated. METHODS: We compared leukocyte count, interleukin-6 (IL-6) levels, arterial blood gases, creatinine clearance, plasma renin activity, cardiothoracic ratio, and clinical outcome in 27 patients without systemic complications who underwent laparoscopic cholecystectomy, including 11 by AWL and 16 by PP. RESULTS: Transient leukocytosis and high IL-6 levels were observed at POD 1 (postoperative day) in both groups, but both values returned to baseline by POD 2. IL-6 levels correlated significantly with operation time (p < 0.01). Changes in blood gases, creatinine clearance, plasma renin activity, and cardiothoracic ratio were not different for the two groups. The clinical outcome was similar for both groups. CONCLUSIONS: Our results indicate that both PP and AWL are appropriate for patients without serious complications.
Adult↗
Molecular studies of bronchial asthma, sarcoidosis and angiotensin converting enzyme inhibitor-induced cough.
The role of genetic factors was reviewed with respect to the pathophysiology of bronchial asthma, sarcoidosis and cough induced by angiotensin converting enzyme (ACE) inhibitor administration. The so-called 'atopy gene' in 11q13 is not linked to atopy but is associated with serum IgE levels. The beta2-adrenergic receptor gene on 5q32-33 was found to have polymorphism by Ban I and to be related to beta2-receptor function; a defect of a 2.3 kb allele is related to lowered sensitivity to beta2-agonists. This defect is also related to higher prevalence on non-atopic bronchial asthma. The occurrence of amino acid mutation (Arg16 to Gly) of beta2-receptors was lower and Gln27 to Glu mutation is extremely rare in the Japanese population compared with Caucasians. There is polymorphism of ACE genotypes among normal subjects and patients with sarcoidosis, II, ID and DD. The genotype is a significant determinant of serum ACE activity and may determine the prognosis of sarcoid patients. Genotype II has a higher incidence of coughing induced by ACE inhibitors.
Alleles↗
Reducing multiple pregnancies by restricting the number of embryos transferred to two at the first embryo transfer attempt.
Though the multiple pregnancy rate in in-vitro fertilization-embryo transfer must be reduced, strict and uniform regulation of the number of embryos transferred may make it impossible for women with little natural fecundity to carry children. We therefore restricted the number of embryos per transfer. In the first half of the observation period (n = 100), we limited the number of embryos transferred to three regardless of the number of previous transfers. In the second half (n = 137), we strictly regulated the number of embryos transferred to two at the first attempt and three in the second and later attempts. The multiple pregnancy rate per pregnancy was significantly lower (P < 0.005) in the second period (20.4%) than in the first period (52.9%), while the clinical pregnancy rate and the implantation rate per transfer were similar in both observation periods. 60.7% (17/28) of the multiple pregnancies arose from the first embryo transfer attempt, and 17.9% (5/28) of them arose from a second attempt. The 18 multiple pregnancies in the first period involved six sets of triplets, while the 10 multiple pregnancies that arose in the second period all involved twins. The implantation rate per transfer at the first attempt was significantly higher than that at the second or later attempts. The criterion for determining the number of embryos transferred should be simple to minimize errors of judgement. We believe that our method of restricting the numbers of embryos transferred may be one method of reducing multiple pregnancies without eliminating the possibility of having children for women with low fecundity.
Adult↗
Secretion of GM-CSF by inflammatory cells in the lung of patients with sarcoidosis.
Several cytokines are involved in the pathophysiology of sarcoidosis. Granulocyte-macrophage colony-stimulating factor (GM-CSF) may be one of these cytokines because its mRNA is expressed by inflammatory cells obtained from the sarcoid lung. We thus asked two questions. Is GM-CSF secreted by bronchoalveolar lavage (BAL) cells? What type of cells express GM-CSF? GM-CSF secreted by the cultured BAL cells from 19 untreated sarcoid patients was measured by an enzyme-linked immunosorbent assay. The individual cells expressing GM-CSF mRNA were identified by in situ hybridization in seven patients. Spontaneous release of GM-CSF by BAL cells was demonstrated in one patient. When stimulated, BAL cells secreted GM-CSF in all subjects studied. In situ hybridization with digoxigenin-labelled GM-CSF cRNA probe revealed that the positive cells were round in shape and larger than lymphocytes, but smaller than large alveolar macrophages that are often irregular in shape. These results strongly indicated that small alveolar macrophages secrete GM-CSF in the sarcoid lesion. This phenomenon may contribute to the enhanced immunological activities observed in sarcoidosis.
Bronchoalveolar Lavage Fluid↗
Hyposensitization attenuates airway inflammation and antigen-induced proliferative response by lymphocytes in a rat model of bronchial asthma.
The mechanism of hyposensitization in bronchial asthma has not been fully elucidated. We established a hyposensitization model of bronchial asthma in rats and examined airway responses and immunological parameters. Brown Norway rats were sensitized by a subcutaneous injection of ovalbumin (OA) at day 1 and by the inhalation of 2% OA aerosol at day 15. Animals were hyposensitized by intraperitoneal injections of OA from day 17 to day 22. They were challenged with OA or acethylcholine (Ach) aerosol at day 23 and changes in intratracheal pressure were recorded. Lungs were lavaged and OA-induced proliferative responses by blood lymphocytes were examined for animals without aerosol challenge at day 23. OA-specific serum IgE levels were measured by enzyme-linked immunosorbent assay. Hyposensitization significantly reduced the OA-induced immediate airway response, accumulation of CD4+ lymphocytes and eosinophils recovered by bronchoalveolar lavage, and the OA-induced proliferative response by blood lymphocytes. The airway responses to Ach and serum OA-specific IgE levels in hyposensitized group were not significantly different from those in the sensitized group. These results indicate that amelioration of airway inflammation and hyporesponsiveness of lymphocytes against OA are involved in the attenuated immediate antigen-induced airway response following hyposensitization.
Acetylcholine↗
Expression of RANTES by bronchoalveolar lavage cells in nonsmoking patients with interstitial lung diseases.
Emphasis has recently been placed on the roles of chemotactic cytokines called chemokines to explain the accumulation of inflammatory cells in the lung that may precede or accompany pulmonary fibrosis in interstitial lung diseases. We hypothesized that RANTES, a member of the C-C chemokines, is one such chemokine. Bronchoalveolar lavage was done in 20 patients with sarcoidosis, 10 patients with interstitial pneumonia associated with collagen vascular disease (CVD-IP), 10 patients with idiopathic pulmonary fibrosis (IPF), and eight healthy volunteers (HV), all of whom were never-smokers. We semiquantitated the spontaneous RANTES mRNA expression by a competitive reverse transcription-polymerase chain reaction (RT-PCR) technique, and measured the levels of RANTES protein by enzyme-linked immunosorbent assay. In all disease groups the expression of RANTES mRNA by bronchoalveolar lavage fluid (BALF) cells and the levels of RANTES protein in BALF were significantly increased compared with those in HV. Patients with sarcoidosis and CVD-IP had a significant positive correlation between the expression of RANTES mRNA by BALF cells and BALF lymphocytosis. The amounts of RANTES mRNA expressed by peripheral blood mononuclear cells and the levels of RANTES protein in serum did not differ among all study groups. Our study demonstrates the adaptability of a semiquantitative RT-PCR method for determining cytokine mRNA expression in vivo. Our results suggest that RANTES may be one of the chemokines that are involved in the mechanism for the accumulation of inflammatory cells in the lung of some distinct interstitial lung diseases.
Bronchoalveolar Lavage↗