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S Fujita

Publications and source records attributed to S Fujita.

At least 55 records · Page 3Linked to original sources
PubMed2002

Association of platelet hyper-aggregability with leukoaraiosis.

OBJECTIVES: To investigate whether there is any relationship between leukoaraiosis and platelet hyper-aggregability of the systemic blood. METHODS: Platelet aggregability, leukoaraiosis, hypertension and hematocrit were assessed in 175 consecutive out-patients attending a regular clinic. Platelet aggregability was estimated by an optical analytical method using two different concentrations each of ADP and collagen (the double ADP method). Hyper-aggregability and non hyper-aggregability were defined with this method. RESULTS: Patients with leukoaraiosis (73 cases) showed a significantly higher incidence of platelet hyper-aggregability than patients with no leukoaraiosis (102 cases) (90.4 vs 56.9%, P=0.000001). Leukoaraiosis was also significantly related to age. Hypertension was a less significant risk factor (P=0.023). CONCLUSIONS: Platelet hyper-aggregability is a significant feature in leukoaraiosis, and appears to be a more important risk factor than hypertension. Normalization of platelet hyper-aggregability might offer an alternative strategy for the prevention of leukoaraiosis in patients with platelet hyper-aggregability, although an interventional study is essential.

Adult↗
PubMed2002

Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes.

Although CD4(+) helper T lymphocytes have been demonstrated to play an important role in antitumor immune response, only a few epitopes of tumor-associated antigens recognized by HLA class II-restricted CD4(+) T lymphocytes have been identified. In the present study, we addressed the question of whether leukemia-associated fusion proteins are recognized by CD4(+) T lymphocytes. Immature dendritic cells (DCs) were loaded with necrotic or apoptotic leukemia cells with t(6;9) or t(9;22) and then cocultured with the dek-can fusion peptide-specific or the bcr-abl fusion peptide-specific CD4(+) T lymphocyte clone. The dek-can peptide-specific and bcr-abl peptide-specific CD4(+) T lymphocyte clones produced interferon-gamma (IFN-gamma) when they were cocultured with HLA-DR-matched but not with mismatched DCs which had been loaded with apoptotic as well as necrotic leukemia cells with t(6;9) and t(9;22), respectively. IFN-gamma production by CD4(+)T lymphocyte clones in response to stimulation with DCs loaded with leukemia cells was inhibited by the anti-HLA-DR monoclonal antibody. These data indicate that the acute myelogenous leukemia-associated fusion protein, dek-can, and chronic myelogenous leukemia-associated fusion protein, bcr-abl, are both processed and presented by DCs to the fusion peptide-specific CD4(+) T lymphocytes.

Antigen Presentation↗
PubMed2002

Clinical, histopathological and immunological distinction in two cases of IgA pemphigus.

Two cases of IgA pemphigus, one of the subcorneal pustular dermatosis (SPD) type and one of the intraepidermal neutrophilic IgA dermatosis (IEN) type, are described. IgA anti-keratinocyte cell surface antibodies reacted only with the uppermost epidermis in the SPD type but with the entire epidermis in the IEN type. A cDNA transfection test for desmocollins (Dsc) revealed that IgA antibodies of the SPD type reacted with Dsc1, but the IEN type did not react with any of the Dsc isoforms (Dsc1-3). ELISA for desmoglein 1 (Dsg1) and Dsg3 showed that neither of the cases had antibodies to Dsg - of either the IgG or IgA subtype. These results confirm that the autoantigen in SPD-type IgA pemphigus is Dsc1, whereas the antigen in most cases of IEN-type IgA pemphigus is unknown.

Aged↗
PubMed2002

The expression of tenascin mRNA in human temporomandibular joint specimens.

The expression of mRNA of tenascin in the temporomandibular joint (TMJ) disc and synovial membrane was examined in 20 human TMJ samples from patients with internal derangement of the TMJ and 10 control specimens by in situ hybridization technique using paraffine-embedded tissue, and antisense and sense cRNA probes. In control specimens, tenascin mRNA was not expressed. However, we were able to find tenascin mRNA expression in the surgical specimens. In 15 of 20 samples, ranging numbers of synovial cells expressed tenascin mRNA in the hypertrophic synovial membranes. Also, in 6 of 20 samples, tenascin mRNA was identified in fibroblasts. In four specimens, vascular endothelial cells were positive for the mRNA. In internal derangement cases, histopathological findings are often found such as synovitis, new capillary growth and fibrosis. The present study demonstrates that tenascin is produced specifically in synovial cells, vascular endothelial cells and fibroblasts affected in the portion of TMJ with internal derangement.

Adult↗
PubMed2002

The expression of cyclooxygenase-2 in human temporomandibular joint samples: an immunohistochemical study.

The aim of this investigation was to evaluate the immunohistochemical expression of cyclooxygenase-2 (COX-2) in the temporomandibular joint (TMJ) and to compare it with that control specimens. Expression of COX-2 in the TMJ disc and the synovial membrane in 26 human TMJ samples (internal derangement of TMJ; n=16, and control; n=10) was measured by an immunohistological technique using paraffin-embedded tissue and specific antihuman COX-2 polyclonal antibody. There were obvious distinction of COX-2 immunoreactivity between the control specimens and internal derangement cases, in the region of posterior and/or anterior loose connective tissues. In particular, intensive COX-2 expression was detected in the synovial membrane of internal derangement cases. The findings of the present study suggest that COX-2 might be an important mechanism regulating inflammation in the synovial membrane with internal derangement of TMJ.

Adult↗
PubMed2002

Cyclic changes of granulocyte colony-stimulating factor (G-CSF) mRNA in the human follicle during the normal menstrual cycle and immunolocalization of G-CSF protein.

BACKGROUND: Ovulation has several similarities with inflammation and is closely connected to the activity of leukocytes and inflammatory cytokines. Since granulocytes are one of the major leukocytes, we focused our attention on the presence and local production of granulocyte colony-stimulating factor (G-CSF) in the human ovary. METHODS: The presence of G-CSF protein in the follicular fluid and perifollicular tissues was examined by Western blot analysis (n = 5) and immunohistochemical staining (n = 10). The relative expression levels of G-CSF mRNA in relation to GAPDH in granulosa, theca and luteal cells during the menstrual cycle were measured by quantitative RT-PCR using TaqMan technology (n = 15). RESULTS: G-CSF protein was detected in all follicular fluid and located mainly in granulosa cells of the follicle and luteal cells. The expression level of G-CSF mRNA in the late follicular phase was 137.6 +/- 18.5, which was approximately 10-fold greater than other phases during the menstrual cycle (P < 0.05). CONCLUSIONS: These results demonstrate that G-CSF is produced in the human follicle shortly before the ovulatory phase and may play an important role in the mechanism of ovulation.

Adult↗
PubMed2002

[Long-term results after surgery for aortic arch nondissection aneurysm].

Between 1990 and August 2001, 109 patients were treated surgically for nondissection fusiform or saccular aortic arch aneurysm. Fifteen patients were emergent. There were 89 male and 20 female patients (mean 71.7 +/- 6, range 49 to 84). Eight patients underwent hemiarch replacement, 57 total arch replacement, 44 distal arch replacement, which were performed with the aid of hypothermic extracorporeal circulation with antegrade selective cerebral perfusion or retrograde cerebral perfusion. The early mortality was 8.5% with elective operations and 53.3% with emergent operations. The incidence of post operative permanent neurological dysfunction was 12.8% with elective operations and 46.7% with emergent operations. The 5-year and 10-year survival rate including in-hospital deaths was 52 +/- 6% and 29 +/- 9%. The 5-year event free rate was 89 +/- 5%.

Aged↗
PubMed2002

[Surgical treatment of Marfan syndrome; analysis of the patients required multiple surgical interventions].

Without treatment, the life expectancy of patients with Marfan syndrome is reduced by the associated cardiovascular abnormalities. In this study, we reviewed our experience of the patients with Marfan syndrome who required multiple surgical interventions to identify the optimal treatment for these patients. Between January 1986 and December 2000, 44 patients with Marfan syndrome were operated on at Shizuoka City Hospital (SCH). Among them, 10 patients (22.7%) underwent multiple surgical interventions. There were 5 male and 5 female patients with a mean age of 40.6 +/- 16.1 years at the initial surgery. Only one patient was operated on at another hospital for his first, second, and third operations. His fourth operation was carried out at SCH. The remaining 9 patients underwent a total of 14 additional surgical procedures at SCH. Computed tomography (CT) scans were taken every 6 months postoperatively, and aortic diameter greater than 60 mm was considered as the indication for the additional surgery. There were no early death and one late death. The causes of additional surgery were enlargement of true aneurysm in 6, enlargement of residual dissection in 4, new dissection in 4, false aneurysm at the coronary anastomosis of Bentall procedure in 1. In 9 patients, both ascending and descending aorta were replaced. Among these 9 patients, only 3 patients underwent total arch replacement, and remaining 6 patients had their arch left in place with or without dissection. Our current strategy of the treatment of Marfan patients with acute type A dissection is total arch replacement with an elephant trunk at the initial emergent surgery.

Adolescent↗
PubMed2001

Design and synthesis of non-peptidic inhibitors for the Syk C-terminal SH2 domain based on structure-based in-silico screening.

Structure-based in-silico screening was carried out for the Syk C-terminal SH2 domain. Fragments that could interact with the pY or pY+1 pockets were selected by our in-silico screening. After tethering two fragments bound to these pockets, we have designed and synthesized new compounds that show favorable interaction with the pY+3 pocket. One such compound, having a cyclohexylmalonic acid moiety identified as a novel potent phosphotyrosyl mimetic, exhibited an affinity comparable to that of the monophosphorylated ligand peptide.

Binding, Competitive↗
PubMed2001

Ca(2+) elevation evoked by membrane depolarization regulates G protein cycle via RGS proteins in the heart.

Regulators of G protein signaling (RGS), which act as GTPase activators, are a family of cytosolic proteins emerging rapidly as an important means of controlling G protein-mediated cell signals. The importance of RGS action has been verified in vitro for various kinds of cell function. Their in situ modes of action in intact cells are, however, poorly understood. Here we show that an increase in intracellular Ca(2+) evoked by membrane depolarization controls the RGS action on G protein activation of muscarinic K(+) (K(G)) channel in the heart. Acetylcholine-induced K(G) current exhibits a slow time-dependent increase during hyperpolarizing voltage steps, referred to as "relaxation." This reflects the relief from the decrease in available K(G) channel number induced by cell depolarization. This phenomenon is abolished when an increase in intracellular Ca(2+) is prevented. It is also abolished when a calmodulin inhibitor or a mutant RGS4 is applied that can bind to calmodulin but that does not accelerate GTPase activity. Therefore, an increase in intracellular Ca(2+) and the resultant formation of Ca(2+)/calmodulin facilitate GTPase activity of RGS and thus decrease the available channel number on depolarization. These results indicate a novel and probably general pathway that Ca(2+)-dependent signaling regulates the G protein cycle via RGS proteins.

Action Potentials↗
PubMed2001

Antiparallel pleated beta-sheets observed in crystal structures of N,N-bis(trichloroacetyl) and N,N-bis(m-bromobenzoyl) gramicidin S.

Despite intensive efforts, the structures of gramicidin S (GS) [cyclo(-Val-Orn-Leu-d-Phe-Pro-)(2)] and its analogues have not been elucidated by the X-ray diffraction method, except for the GS-urea complex (Hull et al., Nature 275, 206-207, 1978; Tishchenko et al., Acta Cryst. D53, 151-159, 1997). We focused on the acetylation of GS to obtain suitable crystals for X-ray diffraction. The amino groups of Orn residues were capped with trichloroacetic and m-bromobenzoic acids. Both trichloroacetyl and m-bromobenzoyl GSs (TcGS and BzGS, respectively) are hydrophobic and their properties are similar to those of acetyl-GS (AcGS). Although it is well known that AcGS yields hexagonal crystals, TcGS and BzGS yield monoclinic and orthorhombic crystals in aqueous dimethylformamide solution, respectively. Their cell volumes were approximately one-fourth or one-eighth of the hexagonal cell volume. The crystal structures of TcGS and BzGS were determined as the first examples of acetylated GS analogues: TcGS, C(64)H(90)N(12)O(12)Cl(6). 3(C(3)H(7)NO), M(r) = 1651.47, monoclinic, P2(1), a = 15.4366(6) A, b = 18.5312(4) A, c = 16.4774(6) A, beta = 14.160(2) degrees, V = 4300.6(2) A(3), Z = 2; and BzGS, C(64)H(98)N(12)O(12)Br(2). 1.54(H(2)O), M(r) = 1535.21, orthorhombic, P2(1)2(1)2(1), a = 16.748(10) A, b = 18.834(5) A, c = 28.558(10) A, V = 9008(7) A(3), Z = 4. Both these peptide molecules formed an antiparallel pleated beta-sheet, and pseudo twofold symmetries existed in the repeated sequence. beta-Turns formed at the fragments of d-Phe-Pro were classified into type II' based on their characteristics. The peptide conformations of TcGS and BzGS were similar to each other, and these structural features agreed with those of structures proposed by the previous studies.

Bromobenzoates↗
PubMed2001

ATRA-regulated Asb-2 gene induced in differentiation of HL-60 leukemia cells.

Suppressors of cytokine signaling (SOCS) proteins possess common structures, a SOCS box at the C-terminus and a SH2 domain at their center. These suppressors are inducible in response to cytokines and act as negative regulators of cytokine signaling. The ASB proteins also contain the SOCS box and the ankyrin repeat sequence at the N-terminus, but do not have the SH2 domain. Although Socs genes are directly induced by several cytokines, no Asb gene inducers have been identified. In this study, we screened the specific genes expressed in the course of differentiation of HL-60 cells, and demonstrated that ASB-2, one of the ASB proteins, was rapidly induced by all-trans retinoic acid (ATRA). Typical retinoid receptors (RARs) or retinoid X receptors (RXRs) binding element (RARE/RXRE) were presented in the promoter of the Asb-2 gene. We showed that RARalpha, one of the RARs, binds to the RARE/RXRE in the Asb-2 promoter. In addition, we demonstrated by luciferase reporter assay that this element was a functional RARE/RXRE. These findings indicate that ASB-2 is directly induced by ATRA and may act as a significant regulator, underlying such physiological processes as cell differentiation.

Adaptor Proteins, Signal Transducing↗
PubMed2001

HLA class II-restricted antigen presentation of endogenous bcr-abl fusion protein by chronic myelogenous leukemia-derived dendritic cells to CD4(+) T lymphocytes.

Bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones have recently been shown to augment colony formation by chronic myelogenous leukemia (CML) cells in a bcr-abl type-specific and HLA class II-restricted manner without addition of exogenous antigen. These findings suggest that CML cells can naturally process and present endogenous bcr-abl fusion protein to CD4+ T lymphocytes in the context of HLA class II molecules. To verify this possibility, the ability of CML-derived dendritic cells (DCs) to present endogenous bcr-abl fusion protein to bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones was investigated. The bcr-abl b3a2 peptide-specific and HLA-DRB1*0901-restricted CD4+ T-lymphocyte clones produced interferon-gamma in response to stimulation with monocyte-derived DCs from HLA-DRB1*0901+ patients with b3a2 type CML. In contrast, DCs from patients with HLA-DRB1*0901- or b2a2 type CML and those from healthy individuals did not exert stimulatory activity on bcr-abl-specific CD4+ T-lymphocyte clones. The response of CD4+ T-lymphocyte clones to CML-derived mature DCs was higher than that to immature DCs and was inhibited by anti-HLA-DR monoclonal antibody. These data suggest that CML-derived DCs can process and present endogenous bcr-abl fusion protein to CD4+ T lymphocytes.

Amino Acid Sequence↗
PubMed2001

Weaning of immunosuppression in living donor liver transplant recipients.

BACKGROUND: Some reported studies have indicated the possibility of immunosuppression withdrawal in cadaveric liver transplantation. The aim of this study was to evaluate the possibility and feasibility of weaning living donor liver transplant recipients from immunosuppression. METHODS: From June of 1990 to October of 1999, 63 patients were considered to be weaned from immunosuppression. They consisted of 26 electively weaned patients and 37 either forcibly or incidentally weaned patients (nonelective weaning) due to various causes but mainly due to infection. Regarding elective weaning, we gradually reduced the frequency of tacrolimus administration for patients who survived more than 2 years after transplantation, maintained a good graft function, and had no rejection episodes in the preceding 12 months. The frequency of administration was reduced from the conventional b.i.d. until the start of weaning to q.d., 4 times a week, 3 times a week, twice a week, once a week, twice a month, once a month, and finally, the patients were completely weaned off with each weaning period lasting from 3 to 6 months. The reduction method of nonelective weaning depended on the clinical course of each individual case. When the patients were clinically diagnosed to develop rejection during weaning, then such patients were treated by a reintroduction of tacrolimus or an additional steroid bolus when indicated. RESULTS: Twenty-four patients (38.1%) achieved a complete withdrawal of tacrolimus with a median drug-free period of 23.5 months (range, 3-69 months). Twenty-three patients (36.5%) are still being weaned at various stages. Sixteen patients (25.4%) encountered rejection while weaning at median period of 9.5 months (range, 1-63 months) from the start of weaning. All 16 were easily treated with the reintroduction of tacrolimus or additional steroid bolus therapy. CONCLUSIONS: We were able to achieve a complete withdrawal of immunosuppression in some selected patients. Although the mechanism of graft acceptance in these patients has yet to be elucidated, we believe that a majority of long-term patients undergoing living donor liver transplantation may, thus, be potential candidates to be successfully weaned from immunosuppression.

Adolescent↗
PubMed2001

Interaction between the RGS domain of RGS4 with G protein alpha subunits mediates the voltage-dependent relaxation of the G protein-gated potassium channel.

1. In native cardiac myocytes, there is a time dependence to the G protein-gated inwardly rectifying K(+) (K(G)) channel current during voltage steps that accelerates as the concentration of acetylcholine is increased. This phenomenon has been called 'relaxation' and is not reproduced in the reconstituted Kir3.1/Kir3.4 channel in Xenopus oocytes. We have shown that RGS4, a regulator of G protein signalling, restores relaxation to the reconstituted Kir3.1/Kir3.4 channel. In this study, we examined the mechanism of this phenomenon by expressing various combinations of membrane receptors, G proteins, Kir3.0 subunits and mutants of RGS4 in Xenopus oocytes. 2. RGS4 restored relaxation to K(G) channels activated by the pertussis toxin (PTX)-sensitive G protein-coupled m(2)-muscarinic receptor but not to those activated by the G(s) protein-coupled beta(2)-adrenergic receptor. 3. RGS4 induced relaxation not only in heteromeric K(G) channels composed of Kir3.1 and Kir3.4 but also in homomeric assemblies of either an active mutant of Kir3.1 (Kir3.1/F137S) or an isoform of Kir3.2 (Kir3.2d). 4. Truncation mutants of RGS4 showed that the RGS domain itself was essential to reproduce the effect of wild-type RGS4 on the K(G) channel. 5. The mutation of residues in the RGS domain which interact with the alpha subunit of the G protein (G(alpha)) impaired the effect of RGS4. 6. This study therefore shows that interaction between the RGS domain and PTX-sensitive G(alpha) subunits mediates the effect of RGS4 on the agonist concentration-dependent relaxation of K(G) channels.

Animals↗
PubMed2001

Low frequency of BCL-2/J(H) translocation in peripheral blood lymphocytes of healthy Japanese individuals.

The incidence of follicular lymphoma differs significantly between white and Japanese individuals. Translocation between the BCL-2 and immunoglobulin heavy chain genes is detected in 85% to 90% of all follicular lymphomas in whites. Recently, BCL-2/J(H) translocation was detected in peripheral blood lymphocytes from more than 50% of healthy white individuals. To clarify the reason for the difference in incidence of follicular lymphoma between whites and Japanese, the frequency of BCL-2/J(H) translocation in peripheral blood lymphocytes of healthy Japanese individuals was compared with that of German individuals. The prevalence of BCL-2/J(H) translocation in Japanese adults appeared to be significantly lower than that in German adults. The present data suggest that the low frequency of BCL-2/J(H) translocation in the Japanese general population may be one of the major reasons for the difference in incidence of follicular lymphoma between whites and Japanese.

Adult↗