Search PubMed⌕ Search

Biomedical subjects

Y Wakatsuki

Publications and source records attributed to Y Wakatsuki.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Immune response to an H. pylori infection in the stomach].

Helicobacter pylori infection associates with chronic infiltration by various cell types including T cells whose cytokine production may regulate local immune response to the bacterium. Indeed in the antral biopsy tissue taken from both H. pylori infected and uninfected stomach, CD3 positive T cells predominate over neutrophils, monocytes and plasma cells. Depending on the rout of antigen priming, these tissue infiltrating T cells play roles either as effector cells of tissue damage or as protecting cells to H. pylori challenge. Emerging evidences suggests that H. pylori infection appear to direct regional immune response to a Th1 type. However, even in the absence of H. pylori infection, almost ninety percent of gastric CD4 T cells are comprised of IFN-gamma producing cells. Therefore activation of tissue infiltrating T cells, either by antigen specific and non-specific manner, would lead to a perpetual inflammation in the H. pylori infected stomach.

Animals↗
PubMed1998

Lysophosphatidylcholine upregulates CD40 ligand expression in newly activated human CD4+ T cells.

Lysophosphatidylcholine (lyso-PC) accumulates in tissues undergoing inflammation and atherosclerosis, where an infiltration of T cells is also seen. We found that lyso-PC increased IFN-gamma production and CD40L expression in CD4+ T cells stimulated with anti-CD3 Ab and recombinant CD80 molecules, whereas lyso-PC did not affect IL-2 and IL-4 production. These results suggest that lyso-PC, in combination with other stimuli, may regulate CD4+ T cell functions to propagate local inflammatory reactions and also imply a novel role played by a modified lipid in the selection of Th1/Th2 immune response as well as in the T cell mediated pathogenesis in atherosclerosis.

Antibodies↗
PubMed1997

Overexpression of B cell-specific activator protein (BSAP/Pax-5) in a late B cell is sufficient to suppress differentiation to an Ig high producer cell with plasma cell phenotype.

The B cell-specific activator protein (BSAP) is a DNA-binding transcription factor expressed in pro-B, pre-B, and mature B cells but not in plasma cells. We explored the role of BSAP in B cell function by creating clones in a late B cell and a plasma cell line transfected with a BSAP expression plasmid. We found that the plasma cell line MPC11, which does not produce BSAP, is still permissive to BSAP production driven by heterologous promoter. Overexpression of BSAP in a late B cell line (CH12.LX.A2) and a plasma cell line augmented cell proliferation and led to greater suppression of Ig synthesis in a late B cell line than in the plasma cell line. The reduction was seen mostly in synthesis of a secretory form of Ig. Overexpression of BSAP reduced Blimp-1 expression in CH12.LX.A2 clones but not in MPC11 clones. In addition, overexpression of BSAP in CH12.LX.A2 cells suppressed spontaneous appearance of cells with high Syndecan-1 expression and high amounts of intracytosolic as well as secreted Ig synthesis. To corroborate the above findings, we cloned nontransfected CH12.LX.A2 cells and found reduced BSAP mRNA expression in the high Ig-secreting clones, which produced more Blimp-1 mRNA with greater Syndecan-1 expression than the low Ig-secreting clones. Taken together, these results indicate that BSAP expression is sufficient to reduce Ig production in late B cells; this effect is mediated in part by suppression of differentiation to cells of plasma-cell phenotype.

Animals↗
PubMed1997

Response of the extramedullary lung plasmacytoma with pleural effusion to chemotherapy.

An elderly patient with extramedullary lung plasmacytoma and subsequent pleural effusion is described. The presence of abnormal plasma cells in the pleural fluid led to diagnosis. Histologically similar conditions such as multiple myeloma and solitary myeloma of bone were ruled out by clinical evaluation. These neoplasms usually occur in the head and neck area and are not characterized by paraprotein accumulation. Few cases in the lung have been reported. We describe a case of extramedullary plasmacytoma of the lung with plasmacytoma-induced pleural effusion and the presence of monoclonal paraprotein in both the serum and urine. Chemotherapy with melphalan was effective in reducing the size of the plasmacytoma, and pleurodesis was used to manage the pleural effusion.

Aged↗
PubMed1997

Helicobacter pylori induces proinflammatory cytokines and major histocompatibility complex class II antigen in mouse gastric epithelial cells.

Although Helicobacter pylori has been reported to stimulate the release of various cytokines from gastric tissue, it remains unknown whether normal and nontumorous gastric epithelial cells produce these cytokines. Therefore, in this study, we used a normal mouse gastric surface mucous cell line (GSM06) to determine whether gastric epithelial cells produce proinflammatory cytokines in response to H. pylori. The expression of MHC class II antigen was also examined, to investigate whether gastric epithelial cells participate in the immune response to H. pylori. In the study, GSM06 cells were incubated with H. pylori or its lipopolysaccharide (LPS). Proinflammatory cytokines were detected by Northern and Western blot analysis. The expression of MHC class II antigen was examined by fluorescence activated cell sorter (FACS) analysis. Genetic expression of proinflammatory cytokines such as interleukin-1alpha, tumor necrosis factor-alpha, and cytokine-induced neutrophil chemoattractant-2beta was enhanced by both intact and sonicated H. pylori, but not by H. pylori LPS. The expression of MHC class II antigen was induced by H. pylori more strongly than by interferon-gamma. We conclude that H. pylori induces the expression of proinflammatory cytokines and MHC class II antigen in gastric epithelial cells. Gastric epithelial cells may act as antigen-presenting cells and participate in the immune response to H. pylori infection.

Animals↗
PubMed1997

Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T lymphocytes.

Atherosclerotic lesions contain substantial numbers of activated T lymphocytes in addition to monocytes/macrophages. T cell-derived cytokines and growth factors may play a role in atherogenesis; however, stimuli responsible for T-cell activation in atherogenesis have not been fully elucidated. In this study, we provide evidence that lysophosphatidylcholine (lyso-PC), a polar phospholipid component increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate gene expression and secretion of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in cultured T lymphocytes isolated from human peripheral blood. Effects of lyso-PC on T lymphocytes appear to be selective and specific, since lyso-PC also increases interleukin (IL)-2 receptor expression but does not affect mRNA levels for IL-2 or IL-4. Lyso-PC-induced upregulation of HB-EGF and IL-2 receptor mRNA in peripheral T cells is mostly dependent on exogenous IL-2 in conditioned medium. The effect of lyso-PC on HB-EGF induction was more potent in CD4+ cells than in CD8+ cells, although lyso-PC increases IL-2 receptor expression dramatically in both CD4+ cells and CD8+ cells. Lyso-PC similarly increased HB-EGF expression in Jurkat cells, a cell line for human CD4+ T lymphocytes. These results in vitro suggest that lyso-PC may be an important stimulus for T cells in atherogenesis in vivo to upregulate HB-EGF and that T cell-derived smooth muscle growth factors may modulate atherosclerotic progression.

Biological Assay↗
PubMed1996

[University education in geriatrics. Present status and future plans of universities regarding the development of a program in geriatrics].

Because the number of people who reach an advanced age has been increasing at an unprecedented rate in Japan, geriatricians are expected to play a central role in health care for the elderly. However, only 16 out of 80 medical schools (20 percent) now have departments of geriatrics for undergraduate education. To develop undergraduate education in the field of geriatrics, a survey was sponsored by the Research Projects on Aging and Health (Health Science Research Grant the Ministry of Health and Welfare of Japan). A questionnaire regarding the present status and future plans of the university about a program in geriatrics, was sent to deans of medical faculties or vice-presidents of medical schools. The questionnaire included questions about current status and future plans regarding undergraduate geriatric education, the presence of a department or clinic of geriatrics, educational requirements in the field of geriatrics, opportunities for practice, institutions of practice, research on geriatrics, and other suggestions. The response rate was 93.7 percent (74/79). Departments or clinics of geriatrics had been established in 15 institutions (20.3 percent) and were planned in 18 (24.3 percent). Undergraduate education in geriatrics was considered necessary in 73 schools (98.7 percent) and indispensable as an obligatory subject in 56 (75.7 percent). Clinical practice was considered more important and effective than lectures in 50 schools (63.3 percent). Coordinated lectures on basic biomedical gerontology (such as mechanism of aging) and geriatric medicine for chronic degenerative diseases such as senile dementia were considered essential to the curriculum. In practicing geriatrics, experience in providing medical care to aged patients as well as social support and a welfare system for the aged is emphasized. Institutions, nursing homes, and geriatric hospitals outside medical schools be easily accessible. It was generally agreed that geriatrics should be taught in advanced classes. In conclusion, medical schools in Japan regard undergraduate education in geriatrics as necessary and agree on the optimal curriculum, but it is not universally implemented.

Education, Medical, Undergraduate↗
PubMed1996

[University education in geriatrics. Opinions of teaching staff on undergraduate education in gerontology and geriatric medicine].

Undergraduate education in gerontology and geriatric medicine has become more important because of a progressive increase in the aged population. To assess curricula in geriatric medicine and to survey the opinions of teaching staffs as to the ideal curriculum, a questionnaire was sent to professors of gerontology and geriatric medicine at 14 medical schools. Responses were obtained from all 14 professors. In all medical schools, students are given lectures in the fifth or sixth year, or both. The total number of hours for the lectures varied from a few hours to 40 hours, and contents of the lectures varied between schools. Medical staffs pointed out that little time is allocated to geriatric medicine. They also emphasized the importance of bedside teaching.

Curriculum↗
PubMed1996

[University education in geriatrics: medical students' understandings of gerontology and geriatric medicine].

With the rapid aging of Japan's population, medical professionals who specialize in geriatric medicine are in unprecedented demand. To meet that demand and to improve the curriculum for teaching geriatric medicine and gerontology in Japan, we surveyed medical students' understandings of these specialties. Students at 14 schools with classes in geriatric medicine and gerontology were surveyed. A questionnaire was sent to sixth-year medical students after their classes had ended. Questionnaires were collected from 849 students (60.1%) at ten medical schools (74.1%). One quarter (24.5%) of the students were satisfied with the contents of the classes in geriatric medicine and gerontology taught in their school, whereas 39.4% were not. These specialties encompass many fields of clinical and basic medicine, and many students found the lectures difficult to understand (41.4%). Inter-school comparisons of the results showed that students' strengths and weaknesses in the various areas of geriatric medicine reflected differences in the contents of the classes among the schools. Only 35.4% of students had ever visited hospitals or other health-related facilities for the elderly. Many students (58.8%) had never lived with elderly people. Most students (63.9%) wanted visits to health-care facilities for the elderly to be included in their regular curriculum. Medical students are conscious of the medical implications of the ageing of Japan's population; 13.2% had volunteered to work with the elderly.

Attitude of Health Personnel↗
PubMed1996

[University education in geriatrics: medical student's opinions on gerontology and geriatric medicine].

With the aging of Japan's population, physicians need to be aware of advances in geriatric medicine. To assess the status of geriatric medicine in undergraduate education, we surveyed of medical student's opinions on gerontology and geriatric medicine. A questionnaire was sent to six-year medical students at a total of 20 schools that did not include geriatric medicine in their curriculum. Responses were obtained from 950 students (47.6%) at 16 schools (80%). Almost half of the students (42%) had experiences in health care facilities for the elderly. Ten percent were content with their education in geriatric medicine education and 59% were not. A total of 41.4% felt that geriatric medicine is difficult because it involves many different subjects. Some students had experience as volunteers working with elderly people; they were aware of the aging of Japan's population, and felt that their training in basic geriatrics and in geriatric diseases was insufficient. A total of 56% agreed that all medical schools should have classes in geriatric medicine and 14% did not. Medical students in the schools without classes in geriatric medicine identified dementia (73%), cerebral vascular accidents (51%), cancer (24%) and osteoporosis (19%) as common in elderly people, with no differences between schools. The corresponding data for medical students in schools with classes in geriatric medicine were dementia (77%), cerebral vascular accidents (44%), osteoporosis (29%), and cancer (16%). Undergraduate medical students seem to be exposed to widely differing curricula with regard to geriatric medicine. We found a lack of uniformity in the teaching of gerontology and geriatric medicine to undergraduate medical students in Japan.

Education, Medical, Undergraduate↗
PubMed1995

The role of BSAP in immunoglobulin isotype switching and B-cell proliferation.

A role for the transcription factor B cell-specific activator protein (BSAP) in switch recombination has been proposed because binding sites for this protein have been found near switch regions of several isotypes. We have attempted to assess BSAP's role by altering the expression of this protein in B cells switching in culture to IgG1. We found that a phosphorothioate oligonucleotide antisense to the BSAP translation initiation site was able, when incubated with B cells, to decrease BSAP activity in nuclear extracts, and that IgG1 expression was reduced in such cells compared to cells incubated with control oligonucleotides. However, it is not clear whether this apparent reduction in switch recombination was mediated by the known BSAP binding sites in the immunoglobulin heavy chain locus because the antisense experiments revealed an additional activity of this protein: it is a rate-limiting regulator of cell proliferation. Down-regulation of BSAP was associated with decreased proliferation, while increasing BSAP (by transfection with a BSAP expression plasmid) increased proliferation. Thus because switch recombination apparently requires cell division, the effect of BSAP down-regulation on switching might have resulted from decreased proliferation. The role of BSAP in B cell proliferation suggests that dysregulation of this protein could contribute to neoplastic transformation of B cells. Because of BSAP's many activities, experiments to elucidate the mechanisms of its effects on switching and proliferation will be challenging.

Animals↗
PubMed1994

The murine Ig 3' alpha enhancer is a target site with repressor function for the B cell lineage-specific transcription factor BSAP (NF-HB, S alpha-BP).

Using electrophoretic mobility shift assays (EMSAs) we have identified several target sites for nuclear proteins in the murine heavy chain Ig 3' alpha enhancer. Two of these sites, denoted oligo-H and oligo-K, were shown by several criteria, including cell distribution and stimulation experiments, EMSA cross-competition studies, and proteolytic clipping bandshift assays, to bind to the same protein identical to the transcription factor B cell lineage-specific activator protein (BSAP) (NF-HB, S alpha-BP). To assess the possible functional role of these BSAP binding sites in the 3' alpha enhancer, we transiently transfected a construct containing a 314-bp 3' alpha enhancer fragment upstream of a luciferase reporter gene in MOPC-315 cells, a plasmacytoma line lacking BSAP. In these cells, co-transfection with a vector expressing recombinant BSAP led to significant reduction in the activity of the 3' alpha enhancer fragment. Conversely, in the mature B lymphoma cell line CH12.LX, a cell line that expresses BSAP and has a less active 3' alpha enhancer, selective BSAP down-regulation by an antisense phosphorothioate oligonucleotide was sufficient to considerably up-regulate 3' alpha enhancer activity, as were mutations of both binding sites that prevented binding of BSAP to the 3' alpha enhancer. Our findings thus suggest that the natural loss of BSAP expression in terminally differentiated plasma cells contributes to the activation of the murine Ig 3' alpha enhancer.

Animals↗
PubMed1994

The B cell-specific transcription factor BSAP regulates B cell proliferation.

The B cell-specific activator protein (BSAP) is a DNA-binding transcription factor expressed in pro-B, pre-B, and mature B cells, but not in plasma cells. In this study, we explored the role of BSAP in B cell function by assessing how the content of this protein varies in cells driven by proliferative stimuli and, conversely, how artificial manipulation of BSAP activity affects cell proliferation. We found that BSAP activity of nuclear extracts increased when B cells were activated by mitogen (lipopolysaccharide [LPS]), antigen receptor-mediated signaling (surface immunoglobulin D [IgD] cross-linking) or T cell-dependent stimulation (CD40 cross-linking). We could suppress BSAP activity by exposure of B cells to phosphorothioate oligonucleotides antisense to the BSAP translation initiation start site, whereas control oligonucleotides were virtually inactive. Antisense-induced BSAP suppression was associated with a striking reduction in LPS-induced proliferation of splenic B cells and in the spontaneous proliferation of B lymphoma cells (CH12.LX), but the antisense oligonucleotide had virtually no effect on proliferation of two cell lines lacking BSAP: the T lymphoma line EL-4 and the plasma cell line MOPC-315. Overexpression of BSAP in splenic B cells or de novo expression in MOPC-315 plasma cells induced by transfection of a BSAP expression plasmid stimulated cell proliferation. Taken together, these results suggest that BSAP activity is a rate-limiting regulator of B cell proliferation. We also found that treatment with the antisense BSAP oligonucleotide downregulated Ig class switching induced by interleukin 4 plus LPS. This effect may be secondary to reduced proliferation or could be mediated through BSAP binding sites in the IgH locus.

Animals↗
PubMed1993

Effect of downregulation of germline transcripts on immunoglobulin A isotype differentiation.

In this study we determined the role of immunoglobulin (Ig) germline transcripts in the isotype switch differentiation of the cloned lymphoma B cell line CH12.LX. In initial studies, we showed that addition of transforming growth factor beta (TGF-beta) and interleukin 4 (IL-4), either alone or in combination, augment switching from membrane (m)IgM+ to mIgA+ cells, and that increased switching is preceded and paralleled by an increase in the steady-state level of alpha germline transcripts (alpha GLT). Interestingly, TGF-beta and IL-4 affect switching in different ways, as shown by the fact that IL-4 increases and TGF-beta decreases the number of dual-positive (mIgM+/mIgA+) cells; in addition, TGF-beta and IL-4 have different effects on the time course of induction of alpha GLT. In subsequent studies, we established that we could downregulate alpha GLT levels in CH12.LX B cells by transfecting an expression vector that can be induced to produce transcripts antisense to the I alpha exon. Using this approach we downregulated alpha GLT in CH12.LX B cells undergoing switching in the presence of TGF-beta and IL-4 and showed that such downregulation led to decreased switching, as evidenced by decreased appearance of dual-positive B cells as well as decreased IgA synthesis relative to IgM synthesis. This result was corroborated by the fact that incubation of CH12.LX cells with phosphorothio-oligo antisense DNA to I alpha sequence also led to a decrease in the number of dual-positive cells and in the IgA/IgM secretion ratio. In summary, IgA isotype differentiation in CH12.LX B cell, particularly the steps necessary for the elaboration of mIgM+/mIgA+ switch intermediate cells, is inhibited by downregulation of alpha GLT; it is therefore apparent that alpha GLT plays a key role in the initial stage of isotype switch differentiation.

B-Lymphocytes↗
PubMed1990

Immunohistochemical localization of vitamin B12 R-binder in salivary gland tumors. Implications for cell differentiation.

Vitamin B12 R-binder, a specific binding protein for vitamin B12, was studied immunohistochemically in normal and 106 neoplastic salivary gland tissues with a monoclonal antibody against vitamin B12 R-binder (R-binder). In normal salivary glands, R-binder localization was restricted to the ductal systems and to mucous acinar cells; serous acinar cells, myoepithelial cells and stromal connective tissues were consistently negative. Among salivary gland tumors, R-binder was present in 87% of pleomorphic adenomas, 100% of monomorphic adenomas, and 40% of adenoid cystic carcinomas; positivity was observed only on luminal surfaces of small ductular elements, indicating that the components closely related to ductal differentiation were rather small in population. R-binder could be detected both in lacunar and non-lacunar cells within chondroid areas of pleomorphic adenomas, suggesting the possibility that chondroid regions arise from metaplastic changes in ductal epithelial cells. In mucoepidermoid tumors, mucous cells and focal squamous cells exhibited cytoplasmic staining. The staining pattern for R-binder in epithelial components of adenolymphomas showed close similarities to those found in normal large excretory ducts. Two acinic cell tumors and one case each of myoepithelioma and malignant myoepithelioma exhibited negative reactivity for R-binder, showing that these neoplasms are solely composed of tumor cells without the characteristics of ductular differentiation. The immunohistochemical examination of salivary gland tumors, employing a monoclonal anti-R-binder antibody, may have some implications for cellular heterogeneity and differentiation in various tumors.

Antibodies, Monoclonal↗
PubMed1989

Immunological characterization and clinical implication of cobalamin binding protein in human gastric cancer.

Cobalamin (vitamin B12) binding protein was purified from gastric cancer extracts and from serum-free culture medium of cancer cell line KATOH-III. The molecular weight, determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was 70,000 and the pI was 2.8 to 3.2. From biochemical and immunological properties, this cobalamin binding protein was considered to be an isoprotein of cobalamin R binder. Monoclonal antibodies were produced against saliva R and cobalamin binding protein in culture medium to study their antigenic determinants. Monoclonal antibody 55-D reacted to an epitope of peptide in both binders, whereas WK-1 and H-12 reacted to determinants of a carbohydrate moiety, including sialic acid, in cancer cell-derived binder. In addition, we carried out an enzyme-linked immunoassay and examined plasma levels of immunoreactive R binder in patients with gastric cancer (n = 72), benign gastrointestinal disease (n = 30), and healthy individuals (n = 40). Even in patients without liver metastasis, the level of immunoreactive R binder detected by monoclonal antibody H-12 was elevated in some patients and decreased after excision of the tumor. R binder was also elevated in cancer tissue extract. Immunoreactive binder was histochemically detected in the cytosol of cancer cells and metaplastic cells of the gastric mucosa. The present findings suggest that cobalamin R binder is de novo synthesized in gastric cancer cells and that its plasma level increases in some patients. This binding protein may be a useful diagnostic and therapeutic parameter.

Adult↗