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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 235 records · Page 13Linked to original sources
PubMed2000

[Treatment of adult acute lymphoblastic leukemia by KHALL-93--long-term outcome].

Twelve previously untreated adult patients with acute lymphoblastic leukemia were treated with a KHALL-93 regimen. The mean age was 46.9 years. Four patients (1/3) were over 60 years old, and 5 were Ph1 positive (42%). The complete remission rate was 100%. The 5-year survival was 50% (6/12). The 5-year event-free survival was 50% (6/12) in total, 71% (5/7) in Ph1 negative patients, and 63% (5/8) in patients younger than 60 years old. These results indicate that a KHALL-93 regimen is an effective therapy for adult acute lymphoblastic leukemia.

Adult↗
PubMed2000

[The effect of acetate ringer solution, 6% hydroxyethyl starch saline and 20% mannitol solution on the serum concentration of propofol continuously infused].

Changes in serum concentrations of propofol after administration of three different fluids were investigated in 42 scheduled surgical patients. Anesthesia was induced with propofol 2 mg.kg-1 and maintained with constant rate infusion of propofol 6 mg.kg-1.hr-1. After achieving a stable depth of anesthesia, 5 ml.kg-1 of acetate Ringer's solution, 6% hydroxyethyl starch saline solution or 20% mannitol solution was infused in 15 minutes. Blood samples each 2 ml were taken before and 0, 5, 15, 30 and 60 minutes after fluid treatment. We measured hemoglobin and hematocrit of the samples for calculating the dilution rate of the plasma with infusion treatment, and determined the serum concentration of propofol by HPLC-spectrofluorometry. After administration of each fluid, the serum concentrations of propofol decreased significantly to 17 +/- 15, 25 +/- 10 and 35 +/- 8%, respectively (mean +/- SEM). The dilution rate of the plasma from the fractional change in blood hemoglobin increased to 0.08 +/- 0.02, 0.24 +/- 0.03, and 0.36 +/- 0.03, respectively. Administration of mannitol might markedly increase distribution volume of propofol, and this can be attributed to osmotic action of mannitol and resultant expansion of extracellular fluid volume. The results of the present investigation suggest that this pharmacokinetic change decreased the concentration of propofol more significantly in mannitol treatment patients than in Ringer's solution or 6% hydroxyethyl starch saline treatment patients.

Anesthesia, Intravenous↗
PubMed2000

Differential expression of the chemokine receptors by the Th1- and Th2-type effector populations within circulating CD4+ T cells.

The in vitro studies have proposed that human Th1 cells favor expression of CXCR3 or CCR5, whereas Th2 cells favor CCR3 and CCR4. In this study, the in vivo relevance of expression of these chemokine receptors on Th cells was investigated in patients with atopic dermatitis (AD) as the Th2-dominated disorder and nonatopic normal individuals. Flow-cytometric analysis using monoclonal antibodies against CXCR3, CCR5, CCR3, and CCR4 disclosed that a substantial proportion of memory (CD45RO+) CD4+ T cells in the blood of AD and normal patients expressed CXCR3, CCR5, or CCR4, but expression of CCR3 on these cells was negligible. Stimulation studies combined with intracellular cytokine staining revealed that the cells capable of producing Th2 cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13, were restricted to the CCR4-expressing population within memory CD4+ T cells. Concerning Th1 cytokine production, interferon-gamma (IFN-gamma)-producing cells resided exclusively in CXCR3-expressing memory CD4+ T cells, although IFN-gamma production was found in both memory CD4+ T cells with and without CCR5 expression. We observed that CCR4-expressing memory CD4+ T cells in the blood were more increased in AD patients as compared with normal patients, whereas CXCR3-expressing memory CD4+ T cells were present in a lower frequency in AD than seen in normal patients. These results suggest that CXCR3 and CCR4, but not CCR5 or CCR3, appear to serve as the useful markers for identification of circulating Th1 and Th2 effector populations.

Adult↗
PubMed2000

[The effect of propofol anesthesia on striatal dopamine of awake freely moving and anesthetized rats examined by in vivo microdialysis study].

We investigated the effect of propofol anesthesia on the level of interstitial dopamine in vivo awake free moving and anesthetized rats brain striatum using microdialysis techniques. Rats were implanted a microdialysis probe to right striatum of the brain and administered intravenously 20 mg.kg-1 of propofol for induction and followed by continuous infusion at 12.5, 25 and 50 mg.kg-1.hr-1 up to 1 hour. The microdialysis probe was perfused with artificial cerebrospinal fluid and dialysates from the probe were determined every 20 minutes by high performance liquid chromatography and electrochemical detection. Propofol anesthesia reduced the amount of dopamine derived from dialysate, but no prolonged increases of dopamine metabolites were observed, as we demonstrated in previous investigation for halothane, isoflurane or sevoflurane anesthesia. We hypothesize that the characteristics of propofol anesthesia for dopamine and its metabolites might contribute to low incidence of postoperative nausea and vomiting in its clinical use.

Anesthesia, Intravenous↗
PubMed2000

[Continuous hepatic arterial infusion of 5-fluorouracil with leucovorin for unresectable liver metastases from colorectal cancer].

Twenty-three patients with liver metastases from colorectal cancer were treated by continuous hepatic arterial infusion chemotherapy with 5-FU and Leucovorin. The regimen was that 500 mg/body of 5-FU with 30 mg/body of Leucovorin was administered continuously for 5 days, followed by no medication for 16 days. The effect of this therapy was evaluated and the relationship between this therapy and the overexpression of vascular endothelial growth factor (VEGF) or microvessel density (MVD) was also studied. Complete response was obtained in 4 patients and partial response in 3 patients; the response rate was 32%. The response rate was 60% in patients who underwent more than 7 courses. The response rate was 44% in patients with positive VEGF and 33% in patients with negative VEGF. The response rate was 50% in patients with an MVD of more than 30 and 33% in patients with an MVD of less than 30. The 3-year survival rate for patients who underwent more than 7 courses was 37.5%. This therapy had to be abandoned in 6 patients due to occlusion of the catheter. Skillful maintenance of the catheter is necessary for a high response rate and satisfactory prognosis using this therapy.

Aged↗
PubMed2000

[Rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a patient receiving chemotherapy for acute leukemia].

This report describes the rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a 53-year-old man receiving chemotherapy for acute leukemia. While undergoing first induction therapy for AML, he developed chest pain, and multiple bilateral infiltrations were seen in chest roentgenograms. Administration of antibiotics, antifungal agents, steroid pulse therapy and G-CSF was begun. Pulmonary cavities with meniscal signs developed. The next day, pneumothorax and hemothorax were noted. Although drainage and mechanical ventilation were performed, the patient died after massive hemoptysis. Invasive pulmonary aspergillosis was diagnosed at autopsy.

Aspergillosis↗
PubMed2000

[Negative-pressure pulmonary edema associated with transurethral resection syndrome].

We described a patient who had developed negative-pressure pulmonary edema associated with severe transurethral resection syndrome. A relatively healthy, 67-yr-old man (171 cm and 77 kg) with hypertrophic prostate was scheduled for transurethral resection of the prostate under spinal anesthesia. The patient was sedated with continuous propofol infusion because of his anxiety and wish of being asleep. Fifty minutes after starting the operation, electrolyte analysis revealed a decrease in serum Na+ concentration (116 mEq.l-1), and 10 mg of furosemide and hypertonic saline were administered. Thirty minutes later, the arterial oxygen saturation dropped suddenly and arterial blood gas analysis suggested marked pulmonary insufficiency (PaO2: 64 mmHg and PaCO2: 59.4 mmHg). The patient's trachea was intubated and endotracheal release of pinkish foamy sputum was observed. Chest X-ray showed severe lung edema. Massive absorption of the irrigation fluid might have decreased the electrolyte concentration (Na+: 101.0 mEq.l-1) and colloid oncotic pressure. No evidence of cardiac failure was observed immediately after the incidence of pulmonary edema with pulmonary catheter monitoring. The patient's airway was almost intact under spontaneous breathing, but augmented negative-pressure derived from intermittent snoring was considered to be sufficient to break hydrostatic balance of pulmonary capillary vessels and lead to severe pulmonary edema.

Aged↗
PubMed2000

Location of tumor and distribution of lymph node metastasis in gastric cancer: lesser curve or greater curve.

BACKGROUND: The aim of this study was to clarify the relationship between the location of tumor and distribution of lymph node metastasis in node-positive gastric cancer. Pathologic findings of tumors in which location of tumors or positive nodes was confined within the lesser or greater curve were evaluated, and candidates of limited resection were assessed. METHODS: A total of 211 patients with node-positive gastric cancer treated by D2 or D3 gastrectomy was studied. Location, size, gross type, and histologic type of tumors, presence or absence of serosal, lymphatic, and vascular invasions, and status of lymph node metastasis were investigated. Tumors were divided into lesser curve tumors, greater curve tumors, and others; and lymph node metastases were classified as lesser curve metastasis, greater curve metastasis, and both curves metastasis. RESULTS: Lesser or greater curve tumors were featured by small size, negative serosal invasion, negative vascular invasion, metastasis confined to the perigastric nodes, and number of positive nodes less than seven. Cases of lesser or greater curve metastasis were featured by tumor location within the lesser or greater curve, small size, grossly superficial type, negative serosal invasion, negative lymphatic invasion, and number of positive nodes less than seven. When size of lesser or greater curve tumors was less than 4 cm, lymph node metastasis was mostly restricted to the same lesser or greater curve. CONCLUSION: Among node-positive gastric cancers, tumors located within the lesser or greater curve were characterized by small size, negative serosal invasion, and a few metastases confined to the perigastric lymph nodes. When tumor size was less than 4 cm and tumor invasion was not into serosa, lesser or greater curve tumors rarely extend into lymph nodes along the other curve. Limited resection or less invasive treatment is acceptable for such small gastric cancers along the lesser or greater curve.

Gastrectomy↗
PubMed1999

Activated Rac1 selectively up-regulates the expression of integrin alpha6beta4 and induces cell adhesion and membrane ruffles of nonadherent colon cancer Colo201 cells.

Functions of small GTPases in integrin expression were investigated when the interaction of nonadherent human colon carcinoma 201 cells with the extracellular matrix (ECM) was examined. By transfection of the constitutively active form of a small GTPase Rac1, Rac V12, adhesion of cells to the ECM increased with concomitant cell spreading and formation of membrane ruffles. Activated Cdc42 and Cdc42 V12, but not wild-type Rac1, Cdc42, or RhoA, also induced the adhesion and spreading of Colo201 cells. This adhesion is integrin beta4 dependent since an antibody for integrin beta4 inhibited the RacV12-dependent cell adhesion and numbers of adhesive cells on laminin-coated plates exceeded those on collagen- and fibronectin-coated plates. By immunofluorescence, in addition to clustering of integrin molecules, expression of integrin alpha6beta4 on the cell surface of Rac V12- and Cdc42 V12-expressing cells was selectively up-regulated without an increase in biosynthesis of alpha6beta4 integrin. Treatment of Rac V12-expressing cells with wortmannin or LY294002, specific inhibitors of phosphoinositide 3-OH kinase, decreased the up-regulated alpha6beta4 and cell adhesion. In light of this evidence, we propose that the regulation of integrin alpha6beta4 expression induced by Rac1 and Cdc42 may play an important role in cell adhesion and tumorigenesis of colon carcinoma cells.

Antibodies, Monoclonal↗
PubMed1999

A single immunization with a plasmid encoding hepatitis C virus (HCV) structural proteins under the elongation factor 1-alpha promoter elicits HCV-specific cytotoxic T-lymphocytes (CTL).

Recent studies have raised the possibility that DNA-based vaccination may prove useful for generating virus-specific cytotoxic T-lymphocytes (CTL) responses. Recently, a plasmid containing the human elongation factor 1alpha(EF1-alpha) promoter, pEF321, was reported to be a versatile expression vector for gene expression in mammalian cells in vitro. In the present study, we assessed the capability of a novel plasmid, pEFCE1E2, encoding hepatitis C virus (HCV) structural proteins (core, E1 and E2) under the EF1-alpha promoter to generate CTL against HCV in vivo. BALB/c mice were immunized with the pEFCE1E2 but not with a plasmid possessing the same cDNA under the cytomegalovirus developed HCV-specific effector cells by a single immunization. These effector cells elicited by pEFCE1E2 immunization were CD8(+) and major histocompatibility complex class I restricted. These studies provided evidence for the potential utility of the EF1-alpha promoter for development of DNA vaccines against HCV infections.

Amino Acid Sequence↗
PubMed1999

Th2-type cytokines modulate IL-6 release by human bronchial epithelial cells.

The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial cells (HBECs), has been found to play a role in IL-4 dependent IgE synthesis. Since the allergic reaction in bronchial asthma is associated with the upregulation of IL-4 and Th2 type of immune response, the purpose of our study was to assess whether IL-4 and related cytokines IL-10 and IL-13 regulate IL-6 release by HBEC s. HBECs were obtained by bronchial brushing, cultured in LHC-9/RPMI 1640. At the third passage the cells were stimulated with cytokines (0.1-20 ng/ml) diluted in unsupplemented media for 24 h. The supernatants were tested for IL-6 content by sandwich ELISA. Unstimulated HBECs produced detectable amounts of IL-6 (368+/-25 pg/ml). Exposure to IL-10 (368+/-22 pg/ml) and IL-13 (395+/-6 pg/ml) resulted in little changes. IL-4 caused a slight but significant increase in IL-6 release (530+/-45 pg/ml), P<0.05, TNFalpha (1657+/-85 pg/ml) and IFNgamma (1953+/-37 pg/ml) showed strong induction of IL-6 release in HBECs (P<0.005 and P<0.001, respectively). Both IL-4 and IL-13 significantly inhibited TNF induced IL-6 release (P<0.01 for both) while augmenting the effect of IFNgamma (P<0.005 and P<0.01, respectively.). IL-10 was without a significant effect. We conclude that Th2-type cytokines IL-4 and IL-13 affect the release of IL-6 by HBECs in response to TNFalpha (inhibition) and IFgamma (augmentation). IL-10 had no effect on the regulation of IL-6 release. Modulation of IL-6 levels by Th2-type cytokines may play a role in allergic reactions through the IL-6 promoting effect on IL-4 mediated IgE production.

Bronchi↗
PubMed1999

Amplitude and frequency modulation of metabolic signals in leukocytes: synergistic role of IFN-gamma in IL-6- and IL-2-mediated cell activation.

Many stimuli cause intracellular concentration oscillations of second messengers or metabolites, which, in turn, may encode information in their amplitudes and frequencies. We now test the hypothesis that synergistic cellular responses to dual cytokine exposure correlate with cross-talk between metabolic signaling pathways of leukocytes. Polarized RAW264.7 macrophages and human neutrophils and monocytes exhibited NAD(P)H autofluorescence oscillation periods of congruent with20 s. IFN-gamma tripled the NAD(P)H oscillatory amplitude for these cells. Although IL-6 had no effect, incubation of cells with IFN-gamma and IL-6 increased both oscillatory amplitude and frequency. Parallel changes were noted after treatment with IFN-gamma and IL-2. However, IL-1beta and TNF-alpha did not display frequency doubling with or without IFN-gamma exposure. To determine whether frequency doubling required complete IFN-gamma signaling or simply metabolic amplitude modulation, an electric field was applied to cells at NAD(P)H troughs, which has been shown to enhance NAD(P)H amplitudes. Electric field application led to frequency doubling in the presence of IL-6 or IL-2 alone, suggesting that amplitude modulation is crucial to synergism. Because NADPH participates in electron trafficking to NO, we tested NO production during cytokine exposure. Although IL-6 and IL-2 alone had no effect, IFN-gamma plus IL-6 and IFN-gamma plus IL-2 enhanced NO release in comparison to IFN-gamma treatment alone. When NO production was examined for single cells, it incrementally increased with the same phase and period as NAD(P)H. We suggest that amplitude and frequency modulation of cellular metabolic oscillations contribute to intracellular signaling synergy and entrain NO production.

Adjuvants, Immunologic↗
PubMed1999

High prevalence of transfusion-transmitted virus among patients with non-B, non-C hepatocellular carcinoma.

BACKGROUND: Many patients with hepatocellular carcinoma are positive for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus (anti-HCV). Recently, transfusion-transmitted virus (TTV) DNA was identified in the serum of patients with non-B, non-C posttransfusion hepatitis. In this study, the prevalence of TTV DNA in the serum of patients with non-B, non-C hepatitis-associated hepatocellular carcinoma was evaluated. METHODS: Fifteen patients with hepatocellular carcinoma negative for HBsAg, antibodies to hepatitis B core antigen (anti-HBc), and anti-HCV antibodies were enrolled in this study (non-B, non-C group). Fifteen patients positive for HBsAg and negative for anti-HCV antibody (HBV group) and another group of patients negative for HBsAg but positive for anti-HCV antibody (HCV group) were also enrolled in this study. Data obtained from 27 healthy subjects negative for both HBsAg and anti-HCV antibody and normal levels of serum alanine aminotransferase represented controls. The healthy control group, the non-B, non-C group, and the HCV group were age-matched. TTV DNA was detected by heminested polymerase chain reaction in which specific primers were used. RESULTS: TTV DNA was detected in 10 of 15 patients (67%) in the non-B, non-C group. This prevalence rate in the non-B, non-C group was significantly higher than that in the HBV group (3 of 15 patients, 20%) and the control group (9 of 27 patients, 33%), but it was not significantly different from that in the HCV group (7 of 15 patients, 47%). The noncancerous hepatic tissue samples of 10 TTV-DNA positive patients in the non-B, non-C group included 2 with chronic hepatitis and 8 with cirrhosis. CONCLUSIONS: This study showed that TTV DNA is frequently detected in the serum of patients with non-B, non-C hepatocellular carcinoma. This result suggests a potential pathogenetic association between hepatocellular carcinoma and TTV infection.

Aged↗
PubMed1999

Nuclear import of RPA in Xenopus egg extracts requires a novel protein XRIPalpha but not importin alpha.

Replication protein A (RPA) is a eukaryotic single-stranded (ss) DNA-binding protein that is essential for general DNA metabolism. RPA consists of three subunits (70, 33 and 14 kDa). We have identified by two-hybrid screening a novel Xenopus protein called XRIPalpha that interacts with the ssDNA-binding domain of the largest subunit of RPA. XRIPalpha homologues are found in human and in Drosophila but not in yeast. XRIPalpha is complexed with RPA in Xenopus egg extracts together with another 90 kDa protein that was identified as importin beta. We have demonstrated that XRIPalpha, but not importin alpha, is required for nuclear import of RPA. Immunodepletion of XRIPalpha from the egg extracts blocks nuclear import of RPA but not that of nucleoplasmin, a classical import substrate. RPA import can be restored by addition of recombinant XRIPalpha. Conversely, depletion of importin alpha blocks import of nucleoplasmin but not that of RPA. GST-XRIPalpha pull-down assay shows that XRIPalpha interacts directly with recombinant importin beta as well as with RPA in vitro. Finally, RPA import can be reconstituted from the recombinant proteins. We propose that XRIPalpha plays the role of importin alpha in the RPA import scheme: XRIPalpha serves as an adaptor to link RPA to importin beta.

Amino Acid Sequence↗
PubMed1999

A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells.

Based on the relative expression of CD11c and CD1a, we have identified three fractions of dendritic cells (DCs) in human peripheral blood, including a direct precursor of Langerhans cells (LCs). The first two fractions were CD11c+ DCs, comprised of a major CD1a+/CD11c+ population (fraction 1), and a minor CD1a-/CD11c+ component (fraction 2). Both CD11c+ fractions displayed a monocyte-like morphology, endocytosed FITC-dextran, expressed CD45RO and myeloid markers such as CD13 and CD33, and possessed the receptor for GM-CSF. The third fraction was comprised of CD1a-/CD11c- DCs (fraction 3) and resembled plasmacytoid T cells. These did not uptake FITC-dextran, were negative for myeloid markers (CD13/CD33), and expressed CD45RA and a high level of IL-3Ralpha, but not GM-CSF receptors. After culture with IL-3, fraction 3 acquired the characteristics of mature DCs; however, the expression of CD62L (lymph node-homing molecules) remained unchanged, indicating that fraction 3 can be a precursor pool for previously described plasmacytoid T cells in lymphoid organs. Strikingly, the CD1a+/CD11c+ DCs (fraction 1) quickly acquired LC characteristics when cultured in the presence of GM-CSF + IL-4 + TGF-beta1. Thus, E-cadherin, Langerin, and Lag Ag were expressed within 1 day of culture, and typical Birbeck granules were observed. In contrast, neither CD1a-/CD11c+ (fraction 2) nor CD1a-/CD11c- (fraction 3) cells had the capacity to differentiate into LCs. Furthermore, CD14+ monocytes only expressed E-cadherin, but lacked the other LC markers after culture in these cytokines. Therefore, CD1a+/CD11c+ DCs are the direct precursors of LCs in peripheral blood.

Antigens, CD1↗
PubMed1999

Chemical and immunochemical characterization of limulus factor G-activating substance of Candida spp.

The limulus test is a well-established method for the diagnosis of both gram (-) sepsis and invasive fungal infection. To diagnose deep-seated fungal infections, a (1-->3)-beta-D-glucan-specific chromogenic kit (Fungitec G test MK) has been developed and applied clinically. It is suggested that the limulus reactive substance was released from the fungi to the blood, however, its chemical properties were not precisely examined in detail because of the limited quantity available. In this study, we used chemically defined liquid medium to culture Candida spp. and collected the water soluble fraction, CAWS. The yield of CAWS was circa 100 mg/l, independent of the strain of Candida. CAWS reacted with limulus factor G (Fungitec G test MK) at concentrations as low as 100 ng/ml. Limulus factor G reactivity of CAWS was sensitive to (1-->3)-beta-glucanase, zymolyase and was, at least in part, bound to ConA-agarose. The ConA-bound fraction also reacted with anti-beta-glucan antibody. CAWS is mainly composed of mannan and (1-->6)-beta-glucan, in addition to protein, assessed by 1H-NMR spectroscopy. CAWS also reacted with typing sera of Candida spp., specific for cell wall mannan. Chemical, immunochemical and biochemical analyses of CAWS strongly suggested that the limulus factor G-activating substance was a mannan-beta-glucan complex, present within the architecture of the yeast cell wall.

Candida↗
PubMed1999

Mechanisms of alcohol-induced hepatotoxicity: studies in rats.

Alcohol treatment results in increases in the release of endotoxin from gut bacteria and membrane permeability of the gut to endotoxin, or both. Females are more sensitive to these changes. Elevated levels of endotoxin activate Kupffer cells to release substances such as eicosanoids, TNF-alpha and free radicals. Prostaglandins increase oxygen uptake and most likely are responsible for the hypermetabolic state in the liver. The increase in oxygen demand leads to hypoxia in the liver, and on reperfusion, alpha-hydroxyethyl free radicals are formed which lead to tissue damage in oxygen-poor pericentral regions of the liver lobule.

Animals↗