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Biomedical subjects

N Fujita

Publications and source records attributed to N Fujita.

At least 73 records · Page 4Linked to original sources
PubMed2001

Subcutaneous infection with Mycobacterium fortuitum after allogeneic bone marrow transplantation.

Reports of cases of mycobacterial infections after SCT are rare. We report a 30-year-old female with a cutaneous infection of Mycobacterium fortuitum 30 months after allogeneic bone marrow transplantation for acute lymphoblastic leukemia. The patient was successfully treated with surgical debridement followed by oral minocycline and clarithromycin. Mycobacterial infections should be considered in SCT patients with undiagnosed refractory chronic cutaneous infection, and surgical debridement is useful for the diagnosis and treatment of such infections.

Adult↗
PubMed2001

CTLA4 gene polymorphism contributes to the mode of onset of diabetes with antiglutamic acid decarboxylase antibody in Japanese patients: genetic analysis of diabetic patients with antiglutamic acid decarboxylase antibody.

AIM: The mode of onset is occasionally similar in Type 1 and Type 2 diabetes mellitus, and some patients with Type 2 diabetes are positive for antiglutamic acid decarboxylase antibody (GAD Ab). We investigated the contribution of Type 1 diabetes susceptibility genes to the progression of the insulin-deficient state and mode of onset of Type 2 diabetes in GAD Ab-positive (GAD-Ab+) patients. We examined the variable number of tandem repeats in the promoter region of the insulin gene (INS-VNTR, insulin-dependent diabetes mellitus (IDDM) 2) and cytotoxic T lymphocyte antigen 4 (CTLA4, IDDM12) as representative of Type 1 diabetes susceptibility genes. METHODS: Patients with Type 2 diabetes who were GAD-Ab+ (n = 51) were selected for this study. In INS-VNTR, the class I allele was classified according to length (1S, 25-38 repeat units; 1M, 39-41 repeat units; 1L, 42-44 repeat units) and the exact class I allele length was analysed by specific polymerase chain reaction (PCR) amplifications. Analyses of classes II and III were performed by Southern blot. CTLA4 gene polymorphism (exon 1 position 49, G/A) was analysed by PCR-restriction fragment length polymorphism. RESULTS: The distribution of INS-VNTR was no different between Type 1 diabetes and Type 2 diabetes with GAD Ab. The allele frequencies of CTLA4 gene polymorphism G and A in Type 2 diabetes/GAD-Ab+ were significantly different from those of Type 1 diabetes/GAD-Ab+ (G: 53%, A: 47% vs. G: 84%, A: 16%; P < 0.0001). CONCLUSIONS: Our data showed that GAD-Ab+ Japanese patients presenting with Type 2 diabetes have shifted A allele while patients with abrupt onset have shifted G allele of CTLA4 gene polymorphism. Our results suggest that immunological function and polymorphism of the CTLA4 gene may contribute to the pathogenesis and progression of Type 1 diabetes.

Abatacept↗
PubMed2001

Disturbances in hepatocellular function during cardiopulmonary bypass using propofol anaesthesia.

BACKGROUND AND OBJECTIVE: Serum hyaluronate is thought to be an indicator of derangement in hepatocellular integrity, and the change in serum hyaluronate is a useful indicator in various liver disorders. We assessed the changes in serum hyaluronate in patients undergoing coronary artery bypass graft surgery. METHODS: Eleven patients scheduled for elective coronary artery bypass graft surgery were studied. An oximetry oxygen saturation catheter was inserted into the right hepatic vein to permit monitoring of hepatic venous oxygen saturation. Perioperative measurements included: haemodynamic variables; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; arterial and hepatic venous plasma concentrations of lactate, arterial ketone body ratio (ratio of acetoacetate to 3-hydroxybutyrate); and arterial and hepatic venous hyaluronate were measured. RESULTS: Arterial and hepatic venous hyaluronate increased during cardiopulmonary bypass compared with the prebypass period. These increases returned to prebypass values after the cessation of bypass (hepatic venous hyaluronate value at the prebypass period: 26 +/- 13 ng mL(-1), during bypass: 77 +/- 40 ng mL(-1); 1 h after bypass: 57 +/- 42 ng mL(-1); 6 h after bypass: 32 +/- 15 ng L(-1), 24 h after bypass; 62 +/- 21 ng mL(-1); mean +/- SD, P < 0.05). The arterial and hepatic venous hyaluronate during cardiopulmonary bypass was correlated with total bilirubin and hepatic venous lactate concentrations 6 h after bypass (arterial hyaluronate at cardiopulmonary bypass period vs. total bilirubin at 6 h after bypass; r=0.793, P=0.0036, hepatic venous hyaluronate during bypass vs. that at 6 h after bypass; r=0.795, P=0.0035). CONCLUSIONS: Hepatocellular integrity might be disturbed during cardiopulmonary bypass when propofol anaesthesia is used.

Alanine Transaminase↗
PubMed2001

Novel mode of transcription regulation by SdiA, an Escherichia coli homologue of the quorum-sensing regulator.

SdiA, an Escherichia coli homologue of the quorum-sensing regulator, controls the expression of the ftsQAZ operon for cell division. Transcription of ftsQ is under the control of two promoters, upstream ftsQP2 and downstream ftsQP1, which are separated by 125 bp. SdiA activates transcription from ftsQP2 in vivo. Here, we demonstrate that SdiA facilitates the RNA polymerase binding to ftsQP2 and thereby stimulates transcription from P2. Gel shift and DNase I footprinting assays indicated that SdiA binds to the ftsQP2 promoter region between -51 and -25 with respect to the P2 promoter. Activation of ftsQP2 transcription by SdiA was observed with a mutant RNA polymerase containing a C-terminal domain (CTD)-deleted alpha-subunit (alpha 235) but not with RNA polymerase containing sigma(S) or a CTD-deleted sigma(D) (sigma(D)529). In good agreement with the transcription assay, no protection of P2 was observed with the RNA polymerase holoenzymes, E sigma(S) and E sigma(D)529. These observations together indicate that: (i) SdiA supports the RNA polymerase binding to ftsQP2; and (ii) this recruitment of RNA polymerase by SdiA depends on the presence of intact sigmaCTD. This is in contrast to the well-known mechanism of RNA polymerase recruitment by protein-protein contact between class I factors and alpha CTD. In addition to the P2 activation, SdiA inhibited RNA polymerase binding to the ftsQP1 promoter and thereby repressed transcription from P1. Gel shift assays indicate weak binding of SdiA to the P1 promoter region downstream from -13 (or +112 with respect to P2). Neither alpha CTD nor sigma CTD are required for this inhibition. Thus, the transcription repression of P1 by SdiA may result from its competition with the RNA polymerase in binding to this promoter.

Bacterial Proteins↗
PubMed2001

Overexpression of Fyn tyrosine kinase causes abnormal development of primary sensory neurons in Xenopus laevis embryos.

The expression and function of the Src family protein tyrosine kinase Fyn in Xenopus laevis embryos have been examined. In situ hybridization analysis demonstrated nervous system-specific expression of Fyn mRNA in tail-bud embryos. However, a class of primary sensory neurons; that is, Rohon-Beard (RB) neurons, which is positive for immunoglobulin superfamily cell adhesion molecules (CAM), neural cell adhesion molecule (N-CAM) and contactin, is devoid of Fyn expression. Injection of Fyn mRNA into one of the blastomeres at the 2-cell stage led to overexpression of Fyn in the injected half of the tail-bud embryos. Immunolabeling of the embryos with anti-HNK-1 antibody revealed that the peripheral axons of RB neurons were partially misguided and bound to each other to form abnormal subcutaneous fascicles. Similar abnormality was induced by injection of the Fyn overexpression vector. The incidence of abnormality appeared dose-dependent, being 68-92% of the injected embryos at 50-400 pg of mRNA. Co-injection of the contactin antisense vector depleted contactin mRNA accumulation without affecting Fyn overexpression and reduced the incidence of the abnormal RB-cell phenotype. However, the N-CAM antisense was ineffective in reducing this abnormality. These results suggest that Fyn can modify signals regulating axonal guidance or fasciculation in the developing X. laevis nervous system and that contactin may affect this action of Fyn.

Animals↗
PubMed2001

Vasoactive intestinal peptide regulates its receptor expression and functions of human keratinocytes via type I vasoactive intestinal peptide receptors.

Vasoactive intestinal peptide has been suggested to play some roles in inflammatory dermatoses such as atopic dermatitis and psoriasis. The aim of this study is to clarify the precise mechanisms of how vasoactive intestinal peptide is implicated in the pathogenesis of these disorders. We investigated the expression of vasoactive intestinal peptide and its receptors in normal human fibroblasts and keratinocytes, as well as in a human epidermal keratinocyte cell line DJM-1, using reverse transcription polymerase chain reaction and northern blotting. Type I VIP receptor mRNA was expressed in normal human keratinocytes and DJM-1 cells, and the latter also expressed type II receptor in lesser amounts. Neither type I nor type II VIP receptor mRNA was detected in fibroblasts, and vasoactive intestinal peptide transcript was not found in any cells examined. Type I VIP receptor mRNA was upregulated by Th1 cytokines (interferon-gamma), Th2 cytokines (interleukin-4), and tumor necrosis factor alpha, as well as vasoactive intestinal peptide itself, suggesting the presence of an autoregulatory loop. Vasoactive intestinal peptide increased cAMP production and cell proliferation of DJM-1 cells, and also induced the production of inflammatory cytokines such as interleukin-6, interleukin-8, and RANTES. The production of cAMP and cytokines was abrogated by a type I VIP receptor selective antagonist, indicating that type I receptor mediates these effects. Overall, these results suggest that upregulation of vasoactive intestinal peptide receptors by cytokines from inflammatory cells in the dermis enhances the proliferation and cytokine production of keratinocytes in response to vasoactive intestinal peptide from nerve endings. This cytokine network around keratinocytes may be involved in the pathogenesis of inflammatory dermatoses.

Cell Division↗
PubMed2001

Erythropoietin modulates angiotensin II- or noradrenaline-induced Ca(2+) mobilization in cultured rat vascular smooth-muscle cells.

BACKGROUND: It has been reported that human recombinant erythropoietin (rHuEpo) modulates the sensitivity of the cardiovascular system to angiotensin II (Ang II) or noradrenaline (NA). In the present study, we explored the effect of rHuEpo on the responsiveness of Ang II- or NA-induced cytosolic free calcium ([Ca(2+)]i) mobilization in cultured rat vascular smooth-muscle cells (VSMC). METHODS: [Ca(2+)]i concentrations in VSMC were measured by using the calcium-sensitive fluorescent dye fura-2. RESULTS: The addition of rHuEpo (250 U/ml) alone induced elevation in [Ca(2+)]i, which remained significantly elevated above basal level for at least 60 min in the presence of extracellular Ca(2+). Pre-incubation with specific protein kinase C (PKC) inhibitor calphostin C (1 micromol/l) significantly reduced the peak and the sustained elevations of [Ca(2+)]i. Pre-treatment with rHuEpo for 60 min increased both basal [Ca(2+)]i and the changes in [Ca(2+)]i by Ang II or NA in a dose-dependent manner in the presence of extracellular Ca(2+). The synergistic effects of rHuEpo with Ang II or NA were also retained when VSMC were bathed in the Ca(2+)-free medium after the pre-incubation of rHuEpo. Conversely, they were diminished in the presence of extracellular Ca(2+) combined with intracellular Ca(2+) release inhibitor 8-(NN-diethylamino)octyl-1,3,4,5-trimethoxybenzoate (TMB-8). The synergistic effects of rHuEpo were also diminished by PKC depletion or by PKC inhibitor. CONCLUSIONS: These observations suggest that rHuEpo has synergistic effects on Ang II- or NA-induced [Ca(2+)]i mobilization, particularly on intracellular Ca(2+) release, in VSMC. This may be a potential mechanism contributing to hypertension associated with rHuEpo therapy.

Angiotensin II↗
PubMed2001

Efficient folding of the insect neuropeptide eclosion hormone by protein disulfide isomerase.

Eclosion hormone is an insect neuropeptide that consists of 62 amino acid residues including three disulfide bonds. We have previously reported its hypothetical 3D structure consisting mainly of three alpha-helices. In this paper, we report the effects of chaperone proteins on the refolding of denatured eclosion hormone in a redox buffer containing reduced and oxidized glutathione. Urea-denatured eclosion hormone was spontaneously reactivated within 1 min with a yield of more than 90%, while beta-mercaptoethanol-denatured eclosion hormone was reactivated in a few minutes with a yield of 75%. Under the same experimental conditions, eclosion hormone treated with beta-mercaptoethanol and urea was reactivated slowly with a yield of 47% over a period of 2 h. Protein disulfide isomerase, a eucaryotic chaperone protein, markedly increased the reactivation yield and rate of the totally denatured hormone. GroE oligomers slightly improved the reactivation yield but peptidyl prolyl isomerase had no influence on yield or rate. We propose that the folding pathway of eclosion hormone involves at least two rate-limiting steps, and that protein disulfide isomerase is likely to be involved in the folding in insect neuronal cells.

Animals↗
PubMed2001

Cross talk between prostacyclin and nitric oxide under shear in smooth muscle cell: role in monocyte adhesion.

We tested the hypothesis that at sites of vascular damage, vessel homeostasis is maintained through the cross talk of shear-induced production of prostacyclin and nitric oxide (NO) in vascular smooth muscle cells (VSMC). Confluent A7r5 cells derived from rat aortic VSMC and mesenteric VSMC were exposed to shear stress at 15 dyn/cm(2) for 90 min with the use of a cone-plate device, and productions of prostacyclin and NO were examined. Shear stress increased cumulative production of prostacyclin by 3- to 3.5-fold and that of NO by 6- to 7.5-fold. Western blot analysis showed that inducible NO synthase protein was expressed after shear stress in both types of VSMC. Inhibition of NO synthase enhanced the shear-induced production of prostacyclin from 40 to 60%. Shear-induced production of NO was suppressed by 70% after treatment with 10(-4) M of indomethacin. A7r5 cells adhesiveness for monocytes was suppressed by 50% after shear stress. This suppression was abolished by pretreatment with 10(-4) M of indomethacin, whereas inhibition of NO synthase only minimally inhibited it. We conclude that there is a cross talk of shear-induced production of prostacyclin and NO in VSMC. At sites of vascular damage, prostacyclin synthesis may prevent monocyte adhesiveness for VSMC through the concomitant enhancement of NO production.

Animals↗
PubMed2001

Acute effect of human cardiotrophin-1 on hemodynamic parameters in spontaneously hypertensive rats and Wistar Kyoto rats.

There is considerable evidence to indicate that humoral factors play an important role in the development of left ventricular hypertrophy. Cardiotrophin-1 (CT-1) is a cytokine that has been shown to induce cardiac hypertrophy in a dose-dependent manner. The aim of the present study was to investigate the acute effect of CT-1 on hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) and to study the relationship between the plasma concentration of CT-1 and its hemodynamic effect. Ten-week-old SHR and age-matched WKY were used. Blood pressure (BP), heart rate (HR) and plasma concentration of CT-1 were measured both before and for 60 min after intravenous bolus injection of human CT-1 (10 microg/kg). CT-1 injection significantly decreased BP and significantly increased HR in SHR and WKY. There were significant differences in BP and HR between the two groups at all time points after injection. The lowest BP, highest HR and maximal plasma concentrations of CT-1 were observed in both groups within 10 min after injection. However, after converting the values into the percentage change from their respective baselines, there were no significant differences between the two groups in BP or HR at any time point. There was also no significant difference between the two groups at any time point in the plasma concentration of CT-1. This study indicates that CT-1 decreases BP and increases HR in both SHR and WKY. The most obvious change occurred within 10 min after injection. However, there was no significant difference in the hypotensive effect of CT-1 on 10-week-old SHR and WKY.

Animals↗
PubMed2001

Clinical characteristics of B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS): comparison of CD5+ with CD5- B-LAHS.

OBJECTIVE: B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) has been increasingly reported in Asia and is regarded as a variant of intravascular lymphomatosis (IVL). Recently CD5 was reported to be expressed in some cases of diffuse large cell lymphoma and IVL. We therefore examined the expression of CD5 on lymphoma cells in B-LAHS and compared the clinical and laboratory data between CD5+ and CD5- B-LAHS. METHODS: The expression of CD5 on lymphoma cells was examined using flow cytometry and immunohistochemical analysis of paraffin sections. The clinical records were reviewed to characterize clinical features. PATIENTS: Twelve patients with B-LAHS; ten men and two women, age ranging from 41 to 82 years (median, 63.5 years) were included in this study. RESULTS: B-LAHS is characterized by fever and hepatosplenomegaly without lymphadenopathy at the initial presentation. Histological examination showed hemophagocytosis and infiltration of lymphoma cells in the bone marrow, and in some cases intravascular proliferation of lymphoid cells characteristic of IVL. All patients showed increased levels of lactate dehydrogenase, C-reactive protein, ferritin and soluble interleukin-2 receptor. In eight of the twelve patients, lymphoma cells were positive for CD5. But no differences were observed in the clinical or laboratory findings between CD5+ B-LAHS and CD5- B-LAHS. CONCLUSION: No clinical differences were observed between CD5+ B-LAHS and CD5- B-LAHS. Further studies are required to elucidate the differences in pathogenesis between these two subgroups of B-LAHS.

Adult↗
PubMed2001

Paraformaldehyde protects of hepatitis C virus particles during ultracentrifugation.

Divergent buoyant densities of hepatitis C virus (HCV) have been reported. If the destruction of HCV particles occurs during the ultracentrifugation process to separate fractions with different densities, an accurate evaluation of the HCV buoyant density is difficult. To examine this concern, changes were examined in HCV RNA titer of each density fraction after paraformaldehyde fixation of virus particles in the sera of 9 patients with chronic HCV infection. Serum was treated with 4% paraformaldehyde, and the density fractions were then separated by ultracentrifugation. The HCV RNA titer of each fraction was determined by reverse transcription-polymerase chain reaction (RT-PCR) assay, and the results were compared with those obtained from the serum without paraformaldehyde fixation. After fixation, the HCV RNA titer was significantly increased in the 1.11-1.14 g/mL fraction (P=0.0018), and decreased in the 1.14-1.17 and 1.17-1.20 g/mL fractions (P=0.0457 and 0.0003, respectively). Using immunogold electron microscopy, it was found that morphologically destroyed HCV particles are present mainly in the 1.17 g/mL fraction of paraformaldehyde-untreated samples, whereas the intact HCV virion particles are present in the 1.12 and 1.14 g/mL fractions of the paraformaldehyde-treated samples. These results suggest that the destruction of HCV virions occurs during the ultracentrifugation process and that paraformaldehyde treatment protects from destruction. It was also considered that the accurate buoyant density of the HCV virion is 1.11-1.14 g/mL. This study describes a useful method for the purification of HCV virions, and provides new insights for elucidating the physicochemical properties of HCV particles.

Adult↗
PubMed2001

[Hopkins syndrome: oral prednisolone was effective for the paralysis].

We describe here a 5-year-old girl who presented flaccid paralysis of the left upper limb after recovery from bronchial asthma. T2-weighted magnetic resonance imaging of the cervical cord revealed a focal high intensity area in the left anterior horn at the C6-C7 level. She was treated with oral prednisolone, and paralysis resolved within two months. Thirty cases of Hopkins syndrome have been reported so far, but its cause remains unknown. Early administration of prednisolone might ameliorate paralysis in this syndrome.

Anti-Inflammatory Agents↗
PubMed2001

[Philadelphia chromosome-positive acute lymphoblastic leukemia with monosomy 7 successfully treated with intermediate- and high-dose ara-C].

A 52-year-old man was admitted for treatment of acute lymphoblastic leukemia (ALL). The bone marrow was hypercellular with 67.2% blasts, which were negative for peroxidase, and expressed CD13, CD33, CD34, CD10 and CD7. Cytogenetic and molecular studies revealed t(9;22) and -7(Ph/-7) with major BCR/ABL rearrangement. The patient was treated with the L-AdVP regimen, but failed to achieve complete remission (CR). He then received two courses of chemotherapy consisting of intermediate- and high-dose cytarabine (ara-C), resulting in CR. This case suggests that Ph/-7 ALL with major BCR/ABL gene rearrangement showing coexpression of myeloid antigens may be sensitive to intermediate- and high-dose ara-C.

Antimetabolites, Antineoplastic↗
PubMed2001

[Therapy-related myeloid leukemia following platinum-based chemotherapy for ovarian cancer].

A 40-year-old woman, who had suffered from AML (M1) in 1983, developed ovarian cancer (stage IIIc) in December 1996 after long-term remission. She underwent surgical resection of the cancer, 10 courses of standard chemotherapy and tandem PBSCT (total dose: CBDCA 6,750 mg, CDDP 200 mg, CPA 16,000 mg, THP-ADR 450 mg). After receiving the last course of chemotherapy in June 1998, she was referred to our hospital in September 1998 because of pancytopenia. Laboratory findings showed pancytopenia with 34% leukemic cells, which were positive for alpha NBE and negative for POX and CAE. Surface-marker analysis of the leukemic cells showed positivity for CD11c, CD33, CD56, and DR, and chromosome analysis revealed 47, XX, +8. The patient was diagnosed as having AML (M5a), and received induction therapy consisting of IDR and Ara-C, which led to complete remission. As she had not received etoposide, this case was thought to have been therapy-related leukemia due to the platinum agents used for treating the ovarian cancer.

Adult↗
PubMed2001

A novel enhancer of insulinotrophic action by high glucose (JTT-608) stimulates insulin secretion from pancreatic beta-cells via a new cellular mechanism.

Insulin secretion from MIN6 cells (a pancreatic beta-cell line) induced by high glucose (greater than 16.8 mM) was potentiated by a novel hypoglycemic agent [trans-4-(4-methylcyclohexyl)-4-oxobutyric acid (JTT-608)] (but not glibenclamide, a sulfonylurea). The extracellular Ca(2+)-free condition, a L-type Ca(2+) channel blocker (nifedipine) and an ATP-sensitive K(+) channel opener, diazoxide, completely inhibited increases in cytosolic free Ca(2+) ([Ca(2+)]i) and insulin secretion evoked by JTT-608 in the presence of extracellular Ca(2+). An electrophysiological study using single-barreled microelectrode techniques demonstrated that membrane potential (V(m)) and input resistance of the cell membrane (R(i)) are depolarized and increased by JTT-608, respectively. The apparent transference number for K(+) was also significantly decreased after the addition of JTT-608. These effects immediately occurred after addition of JTT-608 and very rapidly disappeared after removal of JTT-608, which has not been observed in sulfonylureas. Also, these effects of JTT-608 were diminished, but not completely by diazoxide. JTT-608 did not affect the specific binding of [(3)H]glibenclamide to the sulfonylurea receptor. These findings suggest that JTT-608 mainly inhibits ATP-sensitive K(+) channel activity via a binding site distinct from the sulfonylurea receptor and then depolarizes V(m) to open voltage-dependent L-type Ca(2+) channels. Subsequently, these events stimulate Ca(2+) entry to increase [Ca(2+)]i and induce insulin secretion from MIN6 cells. Therefore, JTT-608 is a unique hypoglycemic agent that enhances high glucose-induced insulin secretion. The present findings indicate that JTT-608 is a more useful new class of therapeutic drug for patients with non-insulin-dependent diabetes mellitus, compared with sulfonylurea derivatives.

ATP-Binding Cassette Transporters↗
PubMed2001

[Assessment of stage IIB lung cancer from the pathological factors].

In our experience, the prognosis of patients with pathological T3N0M0 lung cancer is generally poor, the 5-year survival rate being almost the same as that of patients with stage IIIA disease. Thus, we assessed patients with stage IIB disease by examining the pathological factors, lymphatic invasion, vessel invasion, histological type, differentiation, tumor size, and node dissection. Lymphatic invasion was found to be positive in 20 of 21 cases, patients with T3N0M0 lung cancer, and all of those with positive vessel invasion had a significantly poor prognosis. This indicates that positive lymphatic and vessel invasion could be a prognostic factor predicting a poor outcome. Patients with T3N0M0 lung cancer that are found to have this poor prognostic factor may not be diagnosed as having stage IIB disease.

Aged↗