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Biomedical subjects

T Kawai

Publications and source records attributed to T Kawai.

At least 127 records · Page 7Linked to original sources
PubMed2000

A non-toxic heat shock protein 70 inducer, geranyl-geranyl-acetone, restores the heat shock response in gastric mucosa of protein-malnourished rats.

Acute gastric mucosal lesions caused by stress or noxious stimuli are important to consider in the management of critically or chronically ill patients. Protein malnutrition has been implicated as a risk factor for stress ulcer and subsequent complications in those patients. When male Wistar rats fed a 5% or 20% casein diet for 3 weeks were exposed to restraint and water-immersion stress, the low-protein diet significantly increased the ulcer index. The low-protein diet did not change the level of heat shock factor 1 (HSF1) in gastric mucosa but it did attenuate the HSF1 activation after exposure to the stress, resulting in the inhibition of HSP70 mRNA expression and HSP70 induction in gastric mucosa. HSP70 is crucial for the maintenance of cell integrity during pathophysiologic conditions; therefore the impaired HSP70 induction appeared to at least in part aggravate stress ulcer. We also tested whether a non-toxic HSP70 inducer, geranyl-geranyl-acetone (GGA), effectively improved the mucosal integrity by stimulating HSP70 induction under protein malnutrition. Intragastric administration of GGA (200 mg/kg twice a day) to the protein-malnourished rats for up to 1 week failed to stimulate the HSP70 induction. However, the administration of GGA (200 mg/kg twice a day) for 3 weeks restored HSP70 induction and induced higher resistance against stress ulcer as compared with results in vehicle-treated, normally nourished rats. Our results suggest that GGA may have a potential benefit for the prevention of stress ulcer in chronically or critically ill patients with protein malnutrition.

Animals↗
PubMed2000

T(h)1 transmigration anergy: a new concept of endothelial cell-T cell regulatory interaction.

Stimulation of endothelial cells (EC) with IFN-gamma generates selective enhancement of T(h)1 cell transmigration and induction of MHC class II expression on EC. In the present study, we tested whether antigen presentation by EC could influence transmigrating T cells in an in vitro system. Bacterial antigen presentation by EC from primary culture and after cloning induced antigen-specific anergy of transmigrating T(h)1 clone cells in a MHC class II-dependent manner as characterized by non-responsiveness to subsequent antigen presentation and inability to produce IL-2. This T cell transmigration anergy induced by EC was abrogated by anti-rat CD28 mAb, suggesting that lack of B7 co-stimulatory signals by EC might be related to the induction of anergy. While MHC class II expression on primary and cloned EC was observed after IFN-gamma stimulation, these cells never expressed B7. B7-1 gene-transfected endothelial clone cells (ECC/B7-1) were developed to elucidate the influence of B7 co-stimulation by EC. ECC/B7-1 induced proliferation of T(h)1 clone cells, whereas ECC did not induce proliferation in co-culture of T(h)1 clone cells and EC stimulated with IFN-gamma and antigen. In the transmigration assay, ECC/B7-1 did not induce transmigration anergy of T(h)1 clones or T(h)1 lines unless anti-rat B7-1 blocking mAb was added. Therefore, in rats, the T cell anergy induced during transmigration across a layer of EC seemed to be due to antigen presentation in the absence of B7 on the EC. We introduce the concept of transmigration anergy in this manuscript. Thus, EC can play a critical immune regulatory role in the context of antigen presentation by MHC class II to transmigrating T cells.

Animals↗
PubMed2000

Phenylarsine oxide inhibits heat shock protein 70 induction in cultured guinea pig gastric mucosal cells.

Phenylarsine oxide (PAO) forms a stable ring complex with vicinal dithiols that can be reversed with 2,3-dimercaptopropanol (DMP) but not by dithiothreitol (DTT) or 2-mercaptoethanol (2-ME). PAO at 2 microM or higher inhibited heat shock protein 70 (HSP70) induction within minutes in cultured guinea pig gastric mucosal cells exposed to heat (43 degrees C) for 30 min. PAO did not affect the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1) induced by heat stress, but it completely blocked the binding activity of HSF1 to the heat shock element (HSE), leading to the block of expression of HSP70 mRNA and accumulation of HSP70 in the cells. These inhibitions were completely reversed with 2 microM DMP but not with 0.1 mM DTT or 1 mM 2-ME, suggesting specific interactions between PAO and vicinal dithiol-containing molecules. Thioredoxin (Trx) reversed the inhibition of the binding activity of HSF1 in whole cell extracts prepared from PAO-treated, heat-stressed cells. Our results suggest that PAO may react with vicinal-containing molecules including Trx and specifically block the interaction between HSF1 and HSE.

Animals↗
PubMed2000

Cytokine profiles of T-lymphocytes from gingival tissues with pathological pocketing.

Periodontal disease is an infection in which destruction occurs at sites remote from the infection, resulting in pathological pocketing. Intervening between the infection and the destruction is a dense mononuclear inflammatory infiltrate. It has been suggested that this infiltrate might have characteristics and the destructive potential of Th1-type T lymphocytes. To ascertain the nature of the infiltrates we investigated the expression of mRNA for IL-2, IL-5, and IFN-gamma by gingival mononuclear cells (GMC) from healthy (n = 8) or adult periodontitis (AP) patients (n = 25) by using cytokine-specific reverse-transcription/polymerase-chain-reaction (RT-PCR). GMC, as obtained from patients' tissues, expressed IL-2, IFN-gamma, or IL-5 mRNA. Significantly higher proportions of GMC from AP patients expressed IL-2 and IFN-gamma mRNA than did those from healthy subjects. IFN-gamma was the most consistent cytokine message detected. In other experiments, gingival T-lymphocytes (n = 12) and CD4+ and CD8+ gingival T-lymphocytes (n = 16) were isolated from gingival tissues removed surgically from AP patients. AP gingival T-lymphocytes expressed mRNA for IL-2, IFN-gamma, or IL-6 prior to stimulation. After stimulation with Con A, the cells significantly up-regulated IL-5 and IL-6 message expression. Both CD4+ and CD8+ gingival T-lymphocytes expressed IFN-gamma, IL-5, and some IL-2. This cumulative cytokine profile observed in these experiments is consistent with the predominance of Th1-type cells in pathological tissues and with Th2-type cells, which can also be present, being up-regulated under appropriate stimulation. Importantly, CD4+ and CD8+ lymphocytes were shown to express T1- and T2-type cytokine message, emphasizing the potential for CD8+ T-lymphocytes to participate in periodontal disease pathology.

Adolescent↗
PubMed2000

Pleomorphic carcinoma of the pancreas with massive lymphocytic stromal infiltration and long-term survival after resection.

BACKGROUND: Pleomorphic carcinoma of the pancreas is a rare tumor with an extremely poor prognosis. The mean survival time is reported to be approx 3 mo. CLINICAL AND HISTOLOGICAL FINDINGS: A 56-yr-old Japanese man presenting with general fatigue, loss of weight, and high fever was found to have a large hypervascular mass in the body of the pancreas with regional lymph node metastases. Laboratory investigation revealed leukocytosis, elevated erythrocyte sedimentation rate (ESR), and high serum C-reactive protein (CRP). In addition to distal pancreatectomy, splenectomy and lymph node dissection were performed. Histology showed the presence of pleomorphic large cells with bizarre mono- or multinuclei, growing in sarcomatoid pattern without mutual cohesiveness. Another noticeable finding was massive lymphocytic infiltration of the stroma of the neoplasm. Immunohistochemically, the infiltrating lymphocytes consisted of cytotoxic type of T cells. In addition, in situ hybridization for Epstein-Barr virus-encoded RNA (EBAR-1) was not seen in the tumor cells or in lymphocytes. After surgery the patient did not undergo chemotherapy or radiotherapy. He has been well without recurrence for 8 yr. CONCLUSION: We report a case of pleomorphic carcinoma, possibly lymphoepithelioma-like carcinoma, of the pancreas with massive lymphocytic stromal infiltration and long-term survival after resection. Cytokine responses and cellular immunoreactivity may have contributed to a long-term survival, which is unusual in the common type of pleomorphic carcinoma of the pancreas.

Carcinoma↗
PubMed2000

Acute eosinophilic pneumonia following cigarette smoking.

Two cases of acute eosinophilic pneumonia following cigarette smoking are analyzed for characteristic features. The first patient noted dyspnea 14 days after initiation of smoking. The second patient noted dyspnea 12 days after beginning to smoke. Both cases had characteristic features including occurrence at an age younger than 30 years; less than 1 month duration of cigarette smoking before onset of disease; and no identifiable cause of acute eosinophilic pneumonia apart from smoking. We believe that acute eosinophilic pneumonia following cigarette smoking, which has characteristic features as described above, should be considered as a distinct subtype of AEP.

Acute Disease↗
PubMed2000

Determination of protein deposits on RGP lenses by X-ray photoelectron spectroscopy.

PURPOSE: To establish a novel and objective screening method for evaluating the cleaning efficacy of contact lens care solutions for removal of protein deposits on single rigid gas permeable (RGP) lenses. METHODS: New and unworn RGP lenses containing no nitrogen atoms were incubated in a standard tear protein test solution. Protein deposition on lenses was determined by X-ray photoelectron spectroscopy (XPS) before and after standardized cleaning with commercially available care solutions (daily cleaners A, B) and a wetting/soaking solution or with 0.1w/v% sodium dodecyl sulfate (SDS) as a control. Cleaning efficacy was calculated based on the percentage of nitrogen atoms present in the total elements of the measured XPS scan spectrum. RESULTS: Nitrogen atoms originating from residual protein deposits on RGP lenses after cleaning were determined by XPS. The cleaning efficacy of the wetting/soaking solution was lower (74%) than that of daily cleaners A and B (95%) or SDS (96%) controls. CONCLUSIONS: XPS determination of residual protein deposits is a novel and direct evaluation method for determining the cleaning efficacy of RGP lens care solutions for single lenses.

Contact Lens Solutions↗
PubMed2000

[Evidence-based laboratory medicine--a new trend in laboratory medicine].

The most important target of "evidence-based laboratory medicine(EBLM)", based on the fundamental concept of evidence-based medicine(EBM) is to improve appropriate, effective utilization of laboratory tests through close communication between clinical laboratories and clinicians. It is mandatory for clinicians to know of analytical uncertainty for better utilization of laboratory tests in clinical practice. Furthermore, the improvement of clinical utilization and interpretation of laboratory tests can be expected by supplying the evidences obtained through systematic reviewing or meta-analysis of laboratory tests. In order to pursue these purposes, closer communication and cooperation between laboratories and clinicians are important to obtain an effective consensus. Clinical laboratory must work together with interested clinician(s) for systematic review of laboratory tests. Construction of the ways of better laboratory-clinician communication should be an important paradigm for EBLM which will be an important factor for new revolution of laboratory medicine in future.

Clinical Laboratory Techniques↗
PubMed2000

[Clinical evaluation of cardiac valve surgery combined with coronary artery bypass grafting].

Between 1991 and 1999, 23 cases underwent cardiac valve surgery concomitant with myocardial revascularization at our institution. Twelve cases (group I) had a primary valvular disease combined with coronary atherosclerosis, and other 11 cases (group II) were due to ischemic mitral insufficiency. There were 2 hospital deaths in group I (17%) and 4 in group II (36%). Three deaths in group II underwent left ventricular volume reduction surgery. On the basis of this observation, we concluded severe mitral regurgitation with ischemic cardiomyopathy was a particularly difficult management problem with disappointing clinical results. On the other hands, we considered concomitant revascularization should be done in the case of primary valvular disease when angiographically significant coronary artery stenosis was present.

Aged↗
PubMed2000

[Inflammatory markers, especially the mechanism of increased CRP].

Acute phase proteins are synthesized mainly in the liver cells, induced by various inflammatory cytokines which are produced by activated macrophages/monocytes at the inflammatory sites. C-reactive protein is a principal acute phase protein, and increased most significantly upon various inflammations. False negative results may be recognized in the patients with viral infections, collagen diseases such as SLE, PSS, dermatomyositis, ulcerative colitis, Sjögren's syndrome, leukemia, cerebral infarction, etc.

Biomarkers↗
PubMed1999

Long-term outcome and alloantibody production in a non-myeloablative regimen for induction of renal allograft tolerance.

BACKGROUND: Multilineage chimerism and long-term acceptance of renal allografts has been produced in non-human primates conditioned with a nonmyeloablative regimen. Our study was undertaken to evaluate the immunological and pathological status of long-term survivors and to define the role of splenectomy and of the primarily vascularized kidney in the regimen. METHOD: Monkeys were treated with the basic regimen, including: total body irradiation, thymic irradiation, antithymocyte globulin, donor bone marrow transplantation, and a 4-week course of cyclosporine after which no further immunosuppression was given. They were divided into four groups according to the timing of kidney transplantation (KTx) and splenectomy as follows; group A (n=13): KTx and splenectomy on the day of donor bone marrow transplantation (day 0); group B (n=3): KTx on day 0 without splenectomy; group C (n=7): splenectomy on day 0 but delayed KTx until 3 to 16 weeks post-donor bone marrow transplantation; group D (n=3): both splenectomy and KTx delayed until day 120 post-donor bone marrow transplantation. RESULTS: In group A, 11 of 13 monkeys developed chimerism and 9 monkeys achieved long-term survival of 4 to 70 months without evidence of chronic vascular rejection. Alloantibodies were detected in only one long-term survivor. In contrast, all three monkeys in group B developed alloantibodies and rejected their allografts. In group C, long-term survival without alloantibody production was observed in two of three monkeys that had developed chimerism. In group D, all three recipients were sensitized and rejected the kidney allografts rapidly after transplantation. CONCLUSIONS: 1) Production of anti-donor antibody was prevented in most recipients that developed mixed chimerism in the regimens with splenectomy at the time of donor bone marrow transplantation. 2) If splenectomy is not included in the initial conditioning regimen, induction of B cell tolerance is less likely and the result is late onset of alloantibody production and allograft rejection. 3) Immediate transplantation of the kidney at the time of recipient conditioning is not essential for induction of donor specific hyporesponsiveness by bone marrow transplantation.

Animals↗
PubMed1999

Impairment of natural killer cytotoxic activity and interferon gamma production in CCAAT/enhancer binding protein gamma-deficient mice.

We have investigated in vivo roles of CCAAT/enhancer binding protein gamma (C/EBPgamma) by gene targeting. C/EBPgamma-deficient (C/EBPgamma(2/-)) mice showed a high mortality rate within 48 h after birth. To analyze the roles of C/EBPgamma in lymphoid lineage cells, bone marrow chimeras were established. C/EBPgamma(2/-) chimeras showed normal T and B cell development. However, cytolytic functions of their splenic natural killer (NK) cells after stimulation with cytokines such as interleukin (IL)-12, IL-18, and IL-2 were significantly reduced as compared with those of control chimera NK cells. In addition, the ability of C/EBPgamma(-/-) chimera splenocytes to produce interferon (IFN)-gamma in response to IL-12 and/or IL-18 was markedly impaired. NK cells could be generated in vitro with normal surface marker expression in the presence of IL-15 from C/EBPgamma(2/-) newborn spleen cells. However, they also showed lower cytotoxic activity and IFN-gamma production when stimulated with IL-12 plus IL-18 than control NK cells, as observed in C/EBPgamma(2/-) chimera splenocytes. In conclusion, our study reveals that C/EBPgamma is a critical transcription factor involved in the functional maturation of NK cells.

Animals↗
PubMed1999

Expression of telomerase mRNA component (hTR) in transitional cell carcinoma of the upper urinary tract.

BACKGROUND: Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric repeats onto chromosomal ends using a segment of its RNA component as a template. Its activity has become an established indicator of the diagnosis, biologic behavior, and prognosis of several tumors. However, to the authors' knowledge, no previous study has investigated the diagnostic and prognostic importance of the expression of telomerase RNA component (hTR) in transitional cell carcinoma of the upper urinary tract (TCC-UUT). METHODS: The authors investigated hTR expression using in situ hybridization in 130 cases of TCC-UUT, and also its relation to proliferating cell nuclear antigen (PCNA) immunoreactivity, immunoreactivity for p53 oncoprotein, clinicopathologic parameters, and clinical outcome. RESULTS: Positive hTR expression was recognized in 98.4% of the samples and was apparent within the cytoplasm of tumor cells. In normal urothelium, its expression was restricted to the basal cell layers, whereas in the dysplastic lesions of TCC-UUT it was detected with the same intensity and distribution as in the tumor itself. No correlation was found between hTR expression and clinicopathologic findings, PCNA index, or the expression of p53 oncoprotein, although hTR score did tend to increase with disease stage. In univariate and multivariate analyses of disease free and overall survival rates, high hTR expression was associated with significant decreases in both rates. CONCLUSIONS: The expression of hTR appears to be a useful indicator of prognosis for patients with TCC-UUT. In addition, evidence of up-regulation of hTR may also be useful in the diagnosis of this disease.

Adult↗
PubMed1999

Transforming growth factor-alpha (TGFA): genomic structure, boundary sequences, and mutation analysis in nonsyndromic cleft lip/palate and cleft palate only.

Transforming growth factor-alpha (TGFA) has been proposed as a candidate gene in the etiology of nonsyndromic cleft lip with or without cleft palate (NS-CL/P) and of nonsyndromic cleft palate only (NS-CPO). Biologic support for a role of TGFA arises from its presence at high levels in the epithelial tissue of the medial edge of the palatal shelves at the time of shelf fusion in mice. Genetic support for the role of TGFA in clefting comes from the reported association of TGFA alleles with human NS-CPO and NS-CL/P. In this study we report the sequence and structure of human genomic TGFA and the search for causal TGFA mutations in 250 individuals with NS-CL/P or NS-CPO by conformational analysis of the coding sequence, splice junctions, and a portion of the 3' untranslated region strongly homologous between human and mouse. We confirm that human TGFA is composed of six exons and here report several new sequence substitutions and their frequencies. Five variants in conserved segments may represent rare causes for clefting in humans and provide support for the role of TGFA in facial morphogenesis.

Animals↗
PubMed1999

Peflin, a novel member of the five-EF-hand-protein family, is similar to the apoptosis-linked gene 2 (ALG-2) protein but possesses nonapeptide repeats in the N-terminal hydrophobic region.

The calpain small subunits of sorcin, grancalcin, and ALG-2 constitute a family of the Ca(2+)-binding proteins with five EF-hand-like motifs (penta-EF-hand domain or PEF domain) in their C-terminal regions and hydrophobic domains with variable lengths in their N-terminal regions. Searching the human DNA data base of expressed sequence tags (EST) revealed novel partial sequences similar to, but distinct from, the sequences of the previously known PEF proteins. We isolated a cDNA clone of near full length by 5'- and 3'-RACE (rapid amplification of cDNA end) methods and compared the predicted amino acid sequence (284 residues) of the novel EF-hand protein, named peflin, with those of known PEF proteins. The PEF domain of peflin is most similar to ALG-2 (40.9% identity) among the family, particularly in EF-1 (46.2%) and EF-3 (57.1%) regions. Peflin has a longer N-terminal hydrophobic domain than any other member of the family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. Western blot analysis demonstrated that peflin (30 kDa) was expressed in various nonadherent and adherent cultured human cell lines, including Jurkat, HL60, HeLa, and HT1080. Peflin may play basic roles in Ca(2+) signaling irrespective of cell types.

Amino Acid Sequence↗
PubMed1999

Selective diapedesis of Th1 cells induced by endothelial cell RANTES.

Differentiated CD4 T cells can be divided into Th1 and Th2 types based on the cytokines they produce. Differential expression of chemokine receptors on either the Th1-type or the Th2-type cell suggests that Th1-type and Th2-type cells differ not only in cytokine production but also in their migratory capacity. Stimulation of endothelial cells with IFN-gamma selectively enhanced transmigration of Th1-type cells, but not Th2-type cells, in a transendothelial migration assay. Enhanced transmigration of Th1-type cells was dependent on the chemokine RANTES produced by endothelial cells, as indicated by the findings that Ab neutralizing RANTES, or Ab to its receptor CCR5, inhibited transmigration. Neutralizing Ab to chemokines macrophage-inflammatory protein-1alpha or monocyte chemotactic protein-1 did not inhibit Th1 selective migration. Whereas anti-CD18 and anti-CD54 blocked basal levels of Th1-type cell adherence to endothelial cells and also inhibited transmigration, anti-RANTES blocked only transmigration, indicating that RANTES appeared to induce transmigration of adherent T cells. RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor. Thus, enhancement of Th1-type selective migration appeared to be responsible for the diapedesis induced by interaction between CCR5 on Th1-type cells and RANTES produced by endothelial cells. Further evidence that CCR5 and RANTES play a modulatory role in Th1-type selective migration derives from the abrogation of this migration by anti-RANTES and anti-CCR5 Abs.

Actins↗