PubMed Health⌕ Search

Biomedical subjects

Y Kusunoki

Publications and source records attributed to Y Kusunoki.

At least 19 recordsLinked to original sources
PubMed2006

Characterization of genes for a pollen allergen, Cry j 2, of Cryptomeria japonica.

BACKGROUND: Cry j 2 is one of the major pollen allergens of Cryptomeria japonica. The polymorphism of Cry j 2 isoforms and the conservation of the structure of Cry j 2 in coniferous species remain to be analyzed. METHODS: A cDNA library derived from the pollen of C. japonica was screened using a fragment of Cry j 2 cDNA. Restriction fragment length polymorphism analysis was performed to examine the diversity of Cry j 2 genes. The promoters of Cry j 2 genes were isolated with a commercially available cloning kit. Clonal variations in the expression of Cry j 2 in pollen were examined by RNA gel blot analysis, and the conservation of the structure of the Cry j 2 gene in coniferous species was evaluated by DNA gel blot analysis. RESULTS: We isolated three cDNA clones encoding novel isoforms of Cry j 2. We also sequenced a total of 16 promoter regions from 10 specimens. The sequences of promoter regions of Cry j 2 genes were highly divergent. The amount of Cry j 2 mRNA also varied considerably. The Cry j 2 gene was found to be conserved among species belonging to Taxodiaceae and Cupressaceae but to vary between Taxodiaceae and Pinaceae. CONCLUSIONS: The coding and promoter regions of Cry j 2 genes contain large numbers of polymorphisms. Our analysis revealed large variations in the expression of Cry j 2 at the transcriptional level, and we suggest that conserved homologs of Cry j 2 confer cross-allergenicity among Taxodiaceae and Cupressaceae.

Allergens↗
PubMed2005

Intraoral minor salivary gland tumors: a clinicopathological study of 82 cases.

We present a retrospective study of 82 patients with intraoral minor salivary gland tumors which were diagnosed from 1979 to 2003 in Gifu University Hospital. The histological diagnoses were reevaluated according to the 1991 WHO classification. A total of 82 tumors, consisting of 55 benign and 27 malignant tumors, were found in 28 male and 54 female Japanese patients; the male-to-female ratio was 1:1.9. The mean age of the patients was 51.4+/-18.1 years. The tumors affected the palate (n = 64), the buccal region (n = 10), the upper lip (n = 6), the floor of the mouth (n = 1), and the retromolar region (n = 1). Histologically, the tumors were classified as pleomorphic adenoma (n = 54), papillary cystadenoma (n = 1), adenoid cystic carcinoma (n = 10), mucoepidermoid carcinoma (n = 8), acinic cell carcinoma (n = 3), adenocarcinoma (n = 2), basal cell adenocarcinoma (n = 1), papillary cystadenocarcinoma (n = 1), and carcinoma in pleomorphic adenoma (n = 2). From the results of the present study and review of the literature, it is suggested that the minor salivary gland tumors in Japan may be characterized by a higher incidence of benign tumors, especially of pleomorphic adenoma; a more marked tendency for female predominance; a higher incidence of palatal involvement; and a rarer occurrence of polymorphous low grade adenocarcinoma, in comparison with those reported in the literature from outside of Japan.

Adenocarcinoma↗
PubMed2004

Estimating the number of hematopoietic or lymphoid stem cells giving rise to clonal chromosome aberrations in blood T lymphocytes.

Quantifying the proliferative capacity of long-term hematopoietic stem cells in humans is important for bone marrow transplantation and gene therapy. Obtaining appropriate data is difficult, however, because the experimental tools are limited. We hypothesized that tracking clonal descendants originating from hematopoietic stem cells would be possible if we used clonal chromosome aberrations as unique tags of individual hematopoietic stem cells in vivo. Using FISH, we screened 500 blood T lymphocytes from each of 513 atomic bomb survivors and detected 96 clones composed of at least three cells with identical aberrations. The number of clones was inversely related to their population size, which we interpreted to mean that the progenitor cells were heterogeneous in the number of progeny that they could produce. The absolute number of progenitor cells contributing to the formation of the observed clones was estimated as about two in an unexposed individual. Further, scrutiny of ten clones revealed that lymphocyte clones could originate roughly equally from hematopoietic stem cells or from mature T lymphocytes, thereby suggesting that the estimated two progenitor cells are shared as one hematopoietic stem cell and one mature T cell. Our model predicts that one out of ten people bears a non- aberrant clone comprising >10% of the total lymphocytes, which indicates that clonal expansions are common and probably are not health-threatening.

Adolescent↗
PubMed2003

Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors.

PURPOSE: The well-documented increases in malignant tumours in the A-bomb survivors have recently been supplemented by reports that non-cancer diseases, including cardiovascular disease, may also have increased in incidence with increasing radiation dose. Given that low-level inflammatory responses are widely accepted as a significant risk factor for such diseases, we undertook a detailed investigation of the long-term effects of ionizing radiation on the levels of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) in A-bomb survivors. MATERIALS AND METHODS: Blood samples were taken from 453 participants in a long-term epidemiological cohort of A-bomb survivors. Plasma levels of CRP and IL-6 were measured using standard antibody-mediated procedures. Relationships between CRP or IL-6 levels and radiation dose were then investigated by multivariate regression analysis. Blood lymphocytes from each individual were used for immunophenotyping by flow cytometry with murine monoclonal antibodies to CD3, CD4 and CD8. RESULTS: CRP levels were significantly increased by about 31% Gy(-1) of estimated A-bomb radiation (p=0.0001). Higher CRP levels also correlated with age, male gender, body mass index and a history of myocardial infarction. After adjustments for these factors, CRP levels still appeared to have increased significantly with increasing radiation dose (about 28% increase at 1Gy, p=0.0002). IL-6 levels also appeared to have increased with radiation dose by 9.3% at 1Gy (p=0.0003) and after multiple adjustments by 9.8% at 1Gy (p=0.0007). The elevated CRP and IL-6 levels were associated with decreases in the percentages of CD4(+) helper T-cells in peripheral blood lymphocyte populations. CONCLUSIONS: Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.

Aged↗
PubMed2001

Elevated in vivo frequencies of mutant T cells with altered functional expression of the T-cell receptor or hypoxanthine phosphoribosyltransferase genes in p53-deficient mice.

We have studied the effects of a defect in the p53 gene on spontaneous and radiation-induced somatic mutation frequencies in vivo by measuring T-cell receptor (TCR) and hypoxanthine phosphoribosyltransferase (HPRT) mutant frequencies (MFs) in p53 deficient mice both before and after exposure to X-irradiation. In the absence of irradiation, the TCR and HPRT mutant frequencies were roughly two-fold higher in p53 null (-/-) mice than in wild-type (+/+) mice. Unexpectedly, the TCR and HPRT MFs were slightly lower in heterozygote p53 (+/-) than in wild-type (+/+) mice, however. After 2 weeks 2Gy whole body irradiation the TCR and HPRT MFs were about two-fold higher in the p53 null (-/-) and p53 (+/-) mice than in the wild-type. Taken together, these findings suggest that a defect in the p53 gene may lead to TCR and HPRT mutants being recovered at higher frequencies in both irradiated and unirradiated mice, but it should be emphasized that the effects we have observed are not particularly strong, albeit that they are statistically significant. Interestingly, several of the highest TCR MF values that we observed in the course of our experiments were recorded in p53 (-/-) animals that had developed thymomas and hence appeared to be cancer prone.

Animals↗
PubMed2001

Arrest of human dendritic cells at the CD34-/CD4+/HLA-DR+ stage in the bone marrow of NOD/SCID-human chimeric mice.

Human dendritic cell (DC) precursors were engrafted and maintained in NOD/SCID- human chimeric mice (NOD/SCID-hu mice) implanted with human cord blood mononuclear cells, although no mature human DCs were detected in lymphoid organs of the mice. Two months after implantation, bone marrow (BM) cells of NOD/SCID-hu mice formed colonies showing DC morphology and expressing CD1a in methylcellulose culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha). The CD34-/CD4+/HLA-DR+ cell fraction in NOD/SCID-hu mouse BM generated CD1a(+) cells that were highly stimulatory in mixed leukocyte reactions in culture with GM-CSF and TNF-alpha. These results suggest a strong potential for NOD/SCID-hu BM to generate human DCs, although DC differentiation may be blocked at the CD34-/CD4+/HLA-DR+ stage. (Blood. 2001;97:3655-3657)

Animals↗
PubMed2001

Possible role of natural killer cells in negative selection of mutant lymphocytes that fail to express the human leukocyte antigen-A2 allele.

Increased frequencies of cells carrying mutations at several loci have been found in the blood cells of atomic-bomb (A-bomb) survivors upon testing four or five decades after the bombing. Interestingly, though, we have been unable to demonstrate any radiation-associated increases in the frequencies of mutant blood cells in which human leukocyte antigen (HLA)-A expression has been disrupted; this is true both of preliminary tests on the T cells of a small subset of A-bomb survivors and of the much more extensive study reported here in which we screened a much larger group of survivors for HLA-A2 loss mutations in B cells and granulocytes as well as in T cells. In attempting to explain our inability to detect any increases in HLA-A2-negative cell numbers in HLA-A2 heterozygous individuals exposed to A-bomb irradiation, we decided to test the hypothesis that HLA-A mutant lymphocytes might well have been induced by radiation exposure in much the same way as every other type of mutant we encountered, but may subsequently have been eliminated by the strong negative selection associated with their almost inevitable exposure to autologous natural killer (NK) cells in the bloodstream of each of the individuals concerned. We now report that mutant B lymphocyte cell lines that have lost the ability to express the HLA-A2 antigen do indeed appear to be much more readily eliminated than their parental heterozygous counterparts during co-culture in vitro with autologous NK cells. We make this claim first because we have observed that adding autologous NK cells to in vitro cultures of HLA-A2 heterozygous B or T cell lines appeared to cause a dose-dependent decrease in the numbers of HLA-A2-negative mutants that could be detected over a period of 3 days, and second because when we used peripheral blood HLA-A2 heterozygous lymphocyte cultures from which most of the autologous NK cells had been removed we found that we were able to detect newly-arising HLA-A2 mutant T cells in substantial numbers. Taken together, these results strongly support the hypothesis that autologous NK cells are responsible for eliminating mutant lymphocytes that have lost the ability to express self-HLA class I molecules in vivo, and may well therefore explain why we have been unable to detect increased frequencies of HLA-A2 mutants in samples from any of the 164 A-bomb survivors whose HLA-A2 heterozygote status made their lymphocytes suitable for our tests.

Aged↗
PubMed2001

T-cell responses to mitogens in atomic bomb survivors: a decreased capacity to produce interleukin 2 characterizes the T cells of heavily irradiated individuals.

Significant decreases in the fraction of lymphocytes that are CD4(+) and increases in serum levels of some classes of immunoglobulin have been reported to occur in atomic bomb (A-bomb) survivors and in victims of the Chernobyl nuclear plant accident. To investigate the long-term effects of nuclear radiation on cellular immunity in more detail, we used limiting dilution assays with peripheral blood mononuclear cell preparations to analyze the T-cell responses of 251 A-bomb survivors exposed to less than 0.005 Gy and 159 survivors exposed to more than 1.5 Gy. The percentages of CD2-positive cells that were capable of proliferating in response to phytohemagglutinin (PHA) in the presence of exogenous interleukin 2 (IL2) did not differ substantially between distally exposed and more heavily exposed survivors. The heavily exposed survivors appeared to possess fewer T cells that were capable of proliferating in response to concanavalin A (Con A) or of producing interleukin 2. Assuming that CD4 T cells were the ones primarily responsible for producing IL2 in response to Con A, we were able to estimate how many cells in any given CD4 T-cell population were actually producing IL2. The results indicated that peripheral blood samples from heavily exposed survivors contained significantly fewer IL2-producing CD4 T cells than did similar samples from distally exposed survivors, indicating that significant exposure to A-bomb radiation may have a long-lasting negative effect on the capacity of CD4 T-cell populations to produce IL2.

Adult↗
PubMed2000

NK-mediated elimination of mutant lymphocytes that have lost expression of MHC class I molecules.

Mutant cells generated in vivo can be eliminated when mutated gene products are presented as altered MHC/peptide complexes and recognized by T cells. Diminished expression of MHC/peptide complexes enables mutant cells to escape recognition by T cells. In the present study, we tested the hypothesis that mutant lymphocytes lacking expression of MHC class I molecules are eliminated by autologous NK cells. In H-2b/k F1 mice, the frequency of H-2Kb-negative T cells was higher than that of H-2Kk-negative T cells. The frequency of H-2K-deficient T cells increased transiently after total body irradiation. During recovery from irradiation, H-2Kk-negative T cells disappeared more rapidly than H-2Kb-negative T cells. The disappearance of H-2K-deficient T cells was inhibited by administration of Ab against asialo-GM1. H-2Kk-negative T cells showed higher sensitivity to autologous NK cells in vitro than H-2Kb/k heterozygous or H-2Kb-negative T cells. Adding syngeneic NK cells to in vitro cultures prevented emergence of mutant cells lacking H-2Kk expression but had little effect on the emergence of mutant cells lacking H-2Kb expression. Results in the H-2b/k F1 strain correspond with the sensitivity of parental H-2-homozygous cells in models of marrow graft rejection. In H-2b/d F1 mice, there was no significant difference between the frequencies of H-2Kb-negative and H-2Kd-negative T cells, although the frequencies of mutant cells were different after radiation exposure among the strains examined. H-2b/d F1 mice also showed rapid disappearance of the mutant T cells after irradiation, and administration of Ab against asialo-GM1 inhibited the disappearance of H-2K-deficient T cells in H-2b/d F1 mice. Our results provide direct evidence that autologous NK cells eliminate mutant cell populations that have lost expression of self-MHC class I molecules.

Animals↗
PubMed2000

Reproducibility of diagnosis and its influence on the distribution of lung cancer by histologic type in Osaka, Japan.

The histologic types of lung cancer cases diagnosed in 1979-1980 (n=799) and 1987 (n=587) were independently reviewed by two pathologists in order to investigate the reproducibility of the diagnosis of the histologic type when the WHO classification (1981) was used. The specimens from 354 surgical cases and biopsy or cytology specimens from 1032 non-surgical cases were reviewed. The inter-observer agreement was 87.9% (kappa=0.79) for surgical cases and 81.4% (kappa=0.72) for non-surgical cases. When compared to the original diagnosis, the agreement was 86.8% (kappa=0.78) for surgical and 86.4% (kappa=0.79) for non-surgical cases in 1979-1980 and the agreement was 92.8% (kappa=0.87) for surgical and 89.1% (kappa=0.83) for non-surgical cases in 1987. By histologic type, no difference in the agreement was observed except for large cell carcinoma. The distribution of histologic types after the review differed only slightly (less than 6%) from the original distribution. This suggests that in Osaka, Japan, the diagnosis based on the WHO classification (1981) had only a limited influence on the distribution of histologic types, and is not a major reason for the changing trends in lung cancer incidence by histologic type.

Diagnosis, Differential↗
PubMed2000

Early detection of lung cancer with laser-induced fluorescence endoscopy and spectrofluorometry.

STUDY OBJECTIVES: We performed a clinical trial of laser-induced fluorescence endoscopy (LIFE) for detection of precancerous lesions and cancer including carcinoma in situ (CIS), which are difficult to detect by white-light bronchoscopy. DESIGN: Results with LIFE were compared with the criterion standard, white-light bronchoscopy. The evaluation of these endoscopic results spectrofluorometrically was examined, and pixels of LIFE images composed of digital signals for the intensities of red and green were analyzed. SETTING: Tertiary-level hospital treating referrals and subjects with suspicious results in mass screening. PATIENTS: We examined 65 subjects with suspected lung cancer by both methods, and performed biopsy on 216 lesions. RESULTS: The accuracy of diagnosis by white-light bronchoscopy, with histopathologic results as the standard, was 48.6%. The accuracy by LIFE was 72.7%. The sensitivity of conventional bronchoscopy for detection of severe dysplasia (21 biopsy specimens) or cancer (28 biopsy specimens) was 61.2% and specificity was 85.0%. With results by LIFE added, these values were 89.8% and 78.4%, respectively. Of nine patients with CIS, only LIFE showed one lesion, and only LIFE showed the extent of seven of the lesions. The autofluorescence of eight lesions was measured spectrofluorometrically; normal bronchial tissue, severe dysplasia, and cancerous tissue had spectral differences. The red/green intensity of cancers on histograms of LIFE images generally was greater than the ratios for metaplasia or normal bronchial wall. CONCLUSIONS: Use of both methods should facilitate early detection. Evaluation by spectrofluorometry and analysis of digital signal intensity of results by LIFE make results more objective.

Adult↗
PubMed1999

Dual interaction producing both territorial and schooling behavior in fish.

Fish schools are frequently observed without a leader and an explicit condition forming school. Several models of schooling have been proposed focusing on the influence of neighbors, and introducing probability distributions, while these models are based on the separation of schooling and territorial behavior. We frequently consider the duality of aggregation of animals, in which behavioral patterns involve both attraction and repulsion, antagonistic with each other. The idea of probability does not explain this duality that can provide both schooling and territorial behavior. From these biological facts, we have constructed a behavior model in which the influence of neighbors is formulated by the interface between the states of neighbors and a map of changes in these states. This interface uses a self-similar nowhere differentiable transition map which is temporally constructed, encompassing a crucial duality of repulsive and attractive forces hidden in the interaction among fishes. We tested it with computer simulations against the biological reality of schooling and territorial behavior. Due to the influence neighbors can have on duality, the same model can show both schooling behavior with a high degree of polarization and territorial behavior.

Animals↗
PubMed1999

The emergence of the concept of a tool in food-retrieving behavior of the ants Formica japonica Motschulsky.

We propose a weak definition for the usage of a tool for an ethological study of ants. In particular, we illustrate the usage of a cart in experiments on the transportation of foods by ants as employing a logical structure including a contradiction. The contradiction originates in ruling out the very term 'tool' from the description of the behavior of the animals. Focusing on a self-similar structure underlying the description of a contradiction, we observe a particular time-series sequence of ants' behaviors following a 1/f or Zipf's law. The behaviors following the 1/f or Zipf's law manifest an appropriateness of the notion of a cart as a logical jump.

Animals↗
PubMed1999

Decreased proportion of CD4 T cells in the blood of atomic bomb survivors with myocardial infarction.

Epidemiological studies of the atomic bomb survivors have suggested dose-related increases in mortality from diseases other than cancer. Cardiovascular disease is one such noncancer disease for which increases in both mortality and incidence have been found to be associated with radiation dose. Immunological studies have revealed long-term impairment of T-cell-mediated immunity, especially involving deficiencies of CD4 helper T cells, in atomic bomb survivors. In the present study, we investigated whether decreases in CD4 T cells were associated with myocardial infarction in atomic bomb survivors. Of 1,006 survivors examined to determine the proportion of CD4 T cells in peripheral blood lymphocytes, 18 persons had a history of myocardial infarction. The proportion of CD4 T cells was significantly decreased with increased radiation dose [corrected]. Further, the prevalence of myocardial infarction was significantly greater in individuals with a lower proportion of CD4 T cells. These results suggest that myocardial infarction in atomic bomb survivors may be associated with defects in CD4 helper T cells.

Aged↗
PubMed1999

[Diagnosis of small peripheral lung cancers using spiral computed tomography lung cancer screening].

Small peripheral lung cancers can be detected by spiral or helical computed tomography (CT). We applied mobile spiral CT as the first step in further examination (or secondary screening) for lung cancer. We detected 86 lung cancers per 100,000 persons without spiral CT, and 102 patients with spiral CT. Using the latter method, the resection rate and the rate of early-stage lung cancer increased significantly from 48.6% to 67.3% (p < 0.01) and from 21.1% to 35.1% (p < 0.05), respectively. Good results were obtained with mobile CT, especially in women. The mean tumor size of lung cancer detectable with CT was 7 mm smaller than that detected by the previous method. The mean tumor size was only less than 20 mm in females. Overall 787 lung cancers per 100,000 persons were detected using spiral CT for primary screening (1,039 lung cancers/100,000 in men). We must investigate whether the new CT screening system for lung cancer really leads to a lower mortality rate compared with the previous methods. When small nodular lesions with ground-glass opacity could not be diagnosed, the subsequent period up to 10 months can be used to obtain a final diagnosis, regardless of their malignancy. This paper reports specific findings of small peripheral lung cancers, and review the methods of diagnosis for small-sized tumors.

Carcinoma, Small Cell↗
PubMed1998

T cells specific for a polymorphic segment of CD45 induce graft-versus-host disease with predominant pulmonary vasculitis.

To study the character of graft-vs-host disease (GVHD) induced by T cells specific for hemopoietic cells, T cells specific for a polymorphic segment of CD45 were transferred into CD45 congenic mice. C57BL/6 mice that express the CD45b allele were immunized with a 13 mer peptide representing the polymorphic segment (p257-268) of CD45a protein. Conversely, C57BL/6 mice congenic for CD45a were immunized with the CD45b peptide. CD4+ T cells specific for allelic CD45 peptides were elicited. Importantly, T cells specific for CD45 peptides proliferated specifically and vigorously in response to spleen cells expressing the appropriate polymorphic CD45 protein. T cells specific for CD45 induced a substantial graft-vs-host response (GVHR) with predominant early pulmonary vasculitis and later more widespread interstitial mononuclear cell infiltration and alveolitis. No GVHR was induced in bone marrow chimeras expressing only donor hemopoietic cells. Thus, donor T cell recognition of host hemopoietic cells is sufficient to elicit GVHR, but the classical skin, liver, and gut manifestations of GVHD were not observed. The CD45-specific T cells used secreted Th1 cytokines, but without detectable soluble IL-2. Studies using CD45-specific T cells with different effector functions might allow further dissection of donor cell requirements for GVHD syndromes.

Animals↗