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Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 325 records · Page 18Linked to original sources
PubMed1998

Techniques to improve physicians' use of diagnostic tests: a new conceptual framework.

OBJECTIVES: To review the published literature on interventions aimed at improving physicians' testing practices and propose methodologic standards for these studies and to review selected studies using the PRECEDE framework, a behavioral model that helps categorize interventions based on which behavioral factors are being affected. DATA SOURCES: MEDLINE, EMBASE, and HEALTHStar databases were searched for the years 1966 to January 1, 1998, for English-language articles pertaining to diagnostic testing behavior; bibliographies were scanned to identify articles of potential interest; and researchers in health services, health behavior, and behavior modification were contacted for proprietary and other unpublished articles. STUDY SELECTION: A total of 102 articles were identified that described the results of interventions aimed at changing physicians' testing practices. We included the 49 studies that compared diagnostic testing practices in intervention and control groups. DATA EXTRACTION: Two investigators independently reviewed each article in a blinded fashion using a standard data collection form to obtain a methodologic score and to abstract the key elements of each intervention. DATA SYNTHESIS: On a 38-point methodologic criteria scale, the mean +/- SD score was 13+/-4.4. The desired behavior change was reported in the intervention group in 37 (76%) of 49 studies. Twenty-four (86%) of 28 interventions targeted at many behavioral factors were successful, while 13 (62%) of 21 studies aimed at a single behavioral factor were successful (P=.12). CONCLUSIONS: A majority of interventions to improve physicians' testing practices reported in the literature claimed success, with interventions based on multiple behavioral factors trending toward being more successful. While methodologic flaws hamper drawing strong conclusions from this literature, application of a behavioral framework appears to be useful in explaining interventions that are successful and can facilitate interpretation of intervention results.

Clinical Laboratory Techniques↗
PubMed1998

Biomarkers in long survivors of pediatric acute lymphoblastic leukemia patients: late effects of cancer chemotherapy.

In order to elucidate the late effects of cancer chemotherapy, mutant frequencies (Mfs) at the hypoxanthine phosphoribosyl transferase (hprt) locus were evaluated in pediatric patients with early pre-B acute lymphoblastic leukemia (ALL). Hprt-Mfs were measured at least 2 years after completion of chemotherapy. Ten out of 15 patients were found to have hprt-Mfs exceeding the 99% confidence limits as calculated from observations of healthy controls. Although there was some intraindividual variation, serial measurements of hprt-Mfs with intervals of more than 6 months revealed that hprt-Mfs were fairly stable. Patients with high Mfs tended to have sibling clones as detected by clonality analysis using the T-cell receptor (TCR) rearrangement pattern, but clonality did not have a major effect on the Mfs. On the other hand, Mfs at the TCR locus and sister chromatid exchange frequency were within the normal range in all patients. These data suggest that chemotherapy can cause persistent genotoxicity in vivo in a subset of pediatric ALL patients and that the hprt-Mf is a useful method for measuring such an effect.

Adolescent↗
PubMed1998

Role of histamine H1 and H2 receptor antagonists in the prevention of intimal thickening.

Vascular smooth muscle cell migration to the intima from the media and proliferation in the intima play key roles in atherosclerosis and restenosis after coronary angioplasty. Histamine released from adherent platelets at the injured artery and from mast cells in atheromas has stimulant actions on both smooth muscle cell migration and proliferation, and histamine receptor antagonists abolish the effect of histamine in vitro. The aim of this study was to examine the effect of histamine receptor antagonists on intimal thickening. Endothelial injury in the mouse femoral artery was induced by a photochemical reaction between localized irradiation by green light and intravenously administered rose bengal. The histamine H1 receptor antagonist, diphenhydramine, at a dose of 30 mg/kg or the histamine H2 receptor antagonist, cimetidine, at a dose of 200 mg/kg was intraperitoneally administered to mice for 21 days after endothelial injury. Twenty-one days after endothelial injury, morphometric analysis was performed to measure the cross-sectional areas of the intima and media. Diphenhydramine significantly reduced the intimal area to 1.1 +/- 0.3 (x 10(-3) mm2) compared with the value in the control group, which was 6.2 +/- 1.4 (x 10(-3) mm2), but cimetidine (5.5 +/- 1.9, x 10(-3) mm2) did not. Similarly, the ratio of intimal area to medial area in the diphenhydramine-treated group but not in the cimetidine-treated group was significantly reduced (83%). In the in vitro study, cimetidine inhibited neither proliferation nor migration of mouse vascular smooth muscle cells stimulated by platelet-derived growth factor (PDGF). In contrast, diphenhydramine significantly (P < 0.05) inhibited proliferation in a dose-dependent manner, but did not inhibit migration. These results suggest that diphenhydramine, a histamine H1 receptor antagonist, reduced the formation of intimal hyperplasia, at least in part due to inhibition of cell proliferation. However, cimetidine, a histamine H2 receptor antagonist, was ineffective. Histamine may play a key role in intimal thickening, in part via histamine H1 receptors in this model.

Animals↗
PubMed1998

Crystallization and preliminary X-ray crystallographic analysis of archaeal O6-methylguanine-DNA methyltransferase.

Crystals of archaeal O6-methylguanine-DNA methyltransferase (MGMT) from hyperthermophilic archaeon Pyrococcus kodakaraensis strain KOD1 have been grown at room temperature using polyethylene glycol as a precipitant. The diffraction pattern of the crystal extends to 2.0 A resolution at room temperature upon exposure to Cu Kalpha radiation. The crystal belongs to the space group P212121 with unit-cell dimensions of a = 52.8, b = 86.6 and c = 39.9 A. The presence of one molecule per asymmetric unit gives a crystal volume per protein mass (Vm) of 2.3 A3 Da-1 and a solvent content of 48% by volume. A full set of X-ray diffraction data was collected to 2.0 A Bragg spacings from the native crystal.

Bacterial Proteins↗
PubMed1998

Levels of lipid peroxidation product and glycated hemoglobin A1c in the erythrocytes of diabetic patients.

In diabetes, the glycation and subsequent browning (or glycoxidation) reactions are enhanced by elevated glucose concentrations. It is unclear whether or not the diabetic state per se also induces an increase in the generation of oxygen-derived free radicals (OFRs). There is some evidence, however, that glycation itself may induce the formation of OFRs. OFRs could cause oxidative damage to endogenous molecules. We examined the relationship between the levels of lipid peroxidation and the levels of glycated hemoglobin A1c (GHbA1c) in erythrocytes of diabetic and healthy subjects. Lipid peroxidation was assessed in erythrocyte membrane lipids by monitoring peak height ratios of conjugated linoleic acid (CLA), one of the products of lipid peroxidation, to linoleic acid (LA) using gas chromatography-mass spectrometry (GC/MS). CLA is a collective term used to designate a mixture of positional and geometric isomers of LA in which the double bonds are conjugated. The peak height ratio of CLA to LA was used as a biomarker of lipid peroxidation. GHbA1c, an index of glycemic stress, was measured by high-performance liquid chromatography. There were significantly increased ratios of CLA to LA in diabetic erythrocytes compared with control erythrocytes. These ratios of CLA to LA were also significantly correlated with GHbA1c values. This suggests that glycation via chronic hyperglycemia links lipid peroxidation in the erythrocytes of both diabetic and healthy subjects.

Adult↗
PubMed1998

Solid phase synthesis of oligomannopeptoids that mimic the concanavalin A-binding trimannoside.

Oligomannopeptoids from the dimer to the hexamer were produced by solid phase synthesis and their abilities to bind to concanavalin A (ConA) were assessed. The assessment indicated similarity between the oligomannopeptoids and the naturally occurring oligomannosides in the enthalpy of the binding and the valence number vs binding strength relationship, encouraging the use of the oligomannopeptoids as oligomannoside mimics.

Binding, Competitive↗
PubMed1998

Identification of amine acceptor protein substrates of transglutaminase in liver extracts: use of 5-(biotinamido) pentylamine as a probe.

Transglutaminase is a calcium-dependent enzyme which catalyzes amine incorporation and cross-linking of proteins. To isolate the amine acceptor protein substrates of transglutaminase in mammalian livers, a biotin-labeled primary amine substrate of transglutaminase, 5-(biotinamido) pentylamine, was used for biotin labeling of proteins in the liver extracts by endogenous transglutaminase activity. The biotin-labeled proteins were isolated and recovered by biotin-avidin-affinity chromatography. The obtained proteins were separated by SDS-PAGE. Proteins with molecular masses of 15, 24, 35, 40, 44, 93, and 134 kDa were the main components of labeled proteins in mouse liver extract. In rat and guinea pig liver extracts, 32-, 38-, 40-, 44-, and 134-kDa proteins and28-, 40-, 44-, 55-, 60-, 91-, and 134-kDa proteins were the main components of labeled proteins, respectively.Using amino-terminal amino acid sequence analyses and sequence homology searches, the 38-kDa protein from rat liver was identified as a subunit of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12), and the 28-kDa protein from guinea pig liver was identified as a subunit of glutathione S-transferase (class theta) (EC 2.5.1.18). Both the glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle and glutathione S-transferase (class pi) from human placenta also could be amine acceptors in the amine incorporation catalyzed by guinea pig liver transglutaminase. These results suggest that these enzymes can be modified posttranslationally by cellular transglutaminase.

Amines↗
PubMed1998

Synthesis of 5-thiomannose-containing oligomannoside mimics: binding abilities to concanavalin A.

5-Thiomannose-containing oligomannoside mimics, 5SMan alpha(1,6)Man, 5SMan alpha(1,3)Man, 5SMan alpha(1,6)¿Man alpha(1,3)Man¿, Man alpha(1,6)¿5SMan alpha(1,3)Man¿, and 5SMan alpha(1,6)¿5SMan alpha(1,3)Man¿, were synthesized. Dissociation constants for the binding of these mimics to concanavalin A (ConA) were determined by a fluorescence anisotropy inhibition assay. Comparison of these data with those of the natural oligomannosides and with a crystal structure of the trimannoside-ConA complex established that replacing a ring oxygen atom with a sulfur atom causes about 1 kcal/mol decrease in the binding free energy when the ring oxygen is recognized with a hydrogen bonding.

Concanavalin A↗
PubMed1998

Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose.

BACKGROUND: Positron emission tomography (PET) with 2-deoxy-2-fluoro[18F]-D-glucose (FDG) can provide quantitative information about tumor glucose metabolism. The prognostic value of this technique was evaluated for breast carcinoma patients. METHODS: FDG PET was performed on 70 patients with primary breast carcinoma, and the differential absorption ratio (DAR) was calculated as an index of FDG uptake. Overall and relapse free survival curves were created by the Kaplan-Meier method, and differences between the curves were analyzed with the log rank test. For multivariate analysis, the Cox proportional hazards regression model was used. RESULTS: The mean DAR was 2.61+/-1.61 standard deviation (range, 0.65-9.39). According to the grade of DAR, patients were then classified into high DAR (> or =3.0) and low DAR (<3.0) groups. The high DAR group had significantly worse prognoses for both overall and relapse free survival (P < 0.0005 and P < 0.0001, respectively). In multivariate analysis, DAR was an independent predictor of the relapse free survival of breast carcinoma patients (P=0.0377). CONCLUSIONS: DAR, as determined by FDG PET, may be useful as a prognostic indicator for patients with primary breast carcinoma.

Adult↗
PubMed1998

Involvement of CD40 ligand-CD40 and CTLA4-B7 pathways in murine acute graft-versus-host disease induced by allogeneic T cells lacking CD28.

The blockade of B7, using B7 antagonists such as anti-CD80 and/or -CD86 mAbs or CTLA4Ig in vivo, has been shown to induce an efficient suppression of T cell-mediated immune responses in allograft, allergy, and autoimmune models. However, this treatment does not result in complete tolerance. In this study, we examined CD28-B7-independent activation pathways in the pathogenesis of graft-vs-host disease (GVHD) using allogeneic T cells from CD28-deficient mice. Acute GVHD was induced in the absence of CD28 on donor T cells and its manifestations were obvious in the lymphoid tissues. The CD28-independent GVHD was significantly improved by treatment with anti-CD40 ligand (CD40L) mAb. In contrast, treatment with anti-CD80 plus anti-CD86 mAbs exacerbated the clinical manifestations of GVHD and increased the T cell response against host alloantigen, resulting in the expression of CTLA4, CD40L, and CD25 on splenic T cells. These data suggested that the CD40L-CD40 pathway significantly contributed to the CD28-independent pathogenesis of acute GVHD, whereas the CTLA4-B7 pathway acted protectively in the development of GVHD. These results imply that selectively blockading CD28, instead of disrupting both CD28 and CTLA4, would be a better therapeutic strategy for GVHD. Additionally, the simultaneous use of CD40 antagonists may be advantageous.

Abatacept↗
PubMed1998

Cloning and characterization of the mouse pituitary adenylate cyclase-activating polypeptide (PACAP) gene.

The gene encoding the mouse precursor of pituitary adenylate cyclase-activating polypeptide (PACAP) has been cloned, and its structural organization was determined. Using the 5'-rapid amplification of cDNA ends (RACE) procedure, three types of transcription initiation produced by alternative exon usage of two untranslated alternative exons (exons 1A and 1B) were defined. The PACAP gene spans 6.6kb of genomic DNA and is composed of six exons including the alternative exons. The signal peptide, PACAP-related peptide and mature 38-amino acid PACAP (PACAP-38) are encoded within exons 2, 4 and 5, respectively. The 5'-flanking region of the PACAP gene contains several sequence motifs homologous to cAMP response element, TPA response element, and growth hormone factor-1 binding site. A dinucleotide repeat sequence is present in an intron. In addition, there are di- and tetranucleotide repeat sequences 2.4kb and 3.2kb upstream to the translation start point, respectively. The overall intron-exon organization and the production of the alternate mRNAs of the PACAP gene are markedly similar to those of the growth hormone-releasing hormone (GHRH), supporting the hypothesis that the two genes encoding GHRH or PACAP were originated from a gene duplication. Promoter analysis of the 5'-flanking region of the PACAP gene using a luciferase gene reporter system revealed that the isolated 5'-flanking region has functional promoter activity and is responsible for inducible expression.

Alternative Splicing↗
PubMed1998

Morphometry in the cytologic evaluation of thyroid follicular lesions.

BACKGROUND: The current study was undertaken to evaluate the quantitative estimation of cytologic features on aspirated smears for the preoperative differential diagnosis of follicular lesions of the thyroid. METHODS: The subjects were 60 patients with follicular lesions of the thyroid (including 20 follicular carcinomas, 15 follicular adenomas, and 25 adenomatous goiters) whose histopathologic explorations were conducted fully postoperatively. Using a microscope connected to a computerized video system, the mean nuclear area, the mean nuclear perimeter, the circular rate, the largest to the smallest dimension ratio (LS ratio) of the nuclei, and the coefficient of variation of the nuclear area (NACV) were measured and analyzed. RESULTS: Among the quantitative morphometric parameters of nuclei, the circular rate was significantly higher in the group with adenomatous goiters than those with follicular carcinomas (P < 0.00001) and adenomas (P < 0.005). The group with follicular carcinomas had a higher LS ratio than the group with adenomatous goiters (P < 0.0005). The NACV value increased as the malignant potential of the lesion increased and showed significant differences between the groups. When a NACV of 21.5% was chosen as the cutoff point, the incidence of malignancy was significantly higher in patients with high NACV values than in those with low NACV values (P < 0.00001). Using this borderline value, it was possible to distinguish malignant from benign diseases with a sensitivity of 85.0%, a specificity of 82.5%, and an accuracy of 83.3%. CONCLUSIONS: Preoperative quantitative estimations of cytologic nuclear features are useful for the preoperative differential diagnosis of follicular lesions of the thyroid.

Adenocarcinoma, Follicular↗
PubMed1998

Membrane potential of mesenteric artery from carvedilol-treated spontaneously hypertensive rats.

The effects of chronic treatment of stroke-prone spontaneously hypertensive rats (SHRSP) with carvedilol, an antihypertensive agent which has both alpha- and beta-adrenoceptor-blocking actions, on membrane potential and relaxation of mesenteric resistant artery were studied. Five-week old SHRSP were treated with carvedilol for three months. At 16 weeks, the resting membrane potential of arteries from carvedilol-treated SHRSP was more negative than that of arteries from untreated SHRSP. The magnitude of acetylcholine-induced hyperpolarization in arteries from carvedilol-treated SHRSP was not different from that of arteries from untreated SHRSP. In the presence of noradrenaline, the membrane potential of arteries from carvedilol-treated SHRSP was more negative than that of arteries from untreated SHRSP. The membrane potential of arteries from carvedilol-treated SHRSP in the presence of noradrenaline and acetylcholine was more negative than that of arteries from untreated SHRSP. The acetylcholine-induced relaxation in noradrenaline-precontracted preparations from carvedilol-treated SHRSP was greater than that in preparations from untreated SHRSP and was smaller than that in preparations from Wistar Kyoto rats. Scanning electronmicroscopy showed that carvedilol-treatment decreased the structural abnormalities of the endothelium of arteries from SHRSP. These results indicate that chronic carvedilol treatment made the membrane potential of smooth muscle more negative and improved endothelial function in the mesenteric artery of SHRSP, which may contribute to the antihypertensive effect of carvedilol.

Animals↗
PubMed1998

Monoclonal anti-cardiolipin antibodies from New Zealand Black x New Zealand White F1 mice react to thrombomodulin.

The reactivity with and affinity for thrombomodulin (TM) of monoclonal anti-cardiolipin Abs (MoaCL), derived from a New Zealand Black x New Zealand White F1 (NZB/W F1) mouse, were studied to investigate the pathogenicity of anti-cardiolipin Abs (aCL). Four of eighteen MoaCL were found to react with rabbit TM when examined using ELISA. These four MoaCL also reacted with synthetic peptide that included the epidermal growth factor-like domain of human TM, a binding site for thrombin. The reaction with TM of these four MoaCL was inhibited by bovine thrombin. When the affinity for TM of the MoaCL was determined, the dissociation constants (Kd) ranged from 4.8 x 10(-9) to 4.7 x 10(-8) M. By contrast, examination of the affinity for cardiolipin (CL) gave values from 8.3 x 10(-6) to 7.4 x 10(-5) M. Thus, these MoaCL reacted to TM with a higher affinity than to CL. Moreover, these MoaCL also bound to TM on HUVEC and down-regulated the expression level of TM on the surface of HUVEC due to internalization of TM. The binding of thrombin to TM is known to initiate rapid protein C activation, and complexes of activated protein C and protein S show anticoagulatory activity. Thus, the present studies suggest that certain pathogenic aCL cross-react with TM and induce down-regulation of TM on endothelial cells, followed by induction of thrombosis.

Animals↗