Search PubMed⌕ Search

Biomedical subjects

K Ohta

Publications and source records attributed to K Ohta.

At least 163 records · Page 9Linked to original sources
PubMed2000

Effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats.

OBJECTIVE: To document the effects of propofol on the hemodynamic and inflammatory responses to endotoxemia in an animal model. DESIGN: Randomized, prospective laboratory study. SETTING: University experimental laboratory. SUBJECTS: Thirty-two male rats. INTERVENTIONS: The animals were randomly assigned to one of four groups: a) endotoxemia group (n = 8), which received intravenous Escherichia coli endotoxin (15 mg/kg over 2 mins); b) control group (n = 8), which was treated identically to the endotoxemia group except for the substitution of 0.9% saline for endotoxin; c) propofol group (n = 8), which was treated identically to the control group but also received propofol (10 mg/kg bolus, followed by infusion at 10 mg/kg/hr) immediately after the injection of 0.9% saline; and d) propofol-endotoxemia group (n = 8), which was treated identically to the endotoxemia group with the additional administration of propofol (10 mg/kg bolus, followed by infusion at 10 mg/kg/hr) immediately after endotoxin injection. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial blood gases, and acid-base status were recorded and the blood propofol concentrations and plasma cytokine concentrations were measured during the 5-hr observation. Microscopic findings of lung tissue for each group were obtained at necropsy. The systolic arterial pressure and heart rate of the propofol-endotoxemia group were similar to those of the endotoxemia group. The increases in the plasma cytokine (tumor necrosis factor, interleukin-6, and interleukin-10) concentrations, in the base deficit, and in the infiltration of neutrophils in the air space or vessel walls of the lungs were attenuated in the propofol-endotoxemia group compared with the endotoxemia group. CONCLUSIONS: Propofol attenuated cytokine responses, base deficit, and activation of neutrophils to endotoxemia. These findings suggest that propofol may inhibit inflammatory response and prevent the development of metabolic acidosis during endotoxemia.

Animals↗
PubMed2000

Structure-activity relationship of a novel group of mammalian DNA polymerase inhibitors, synthetic sulfoquinovosylacylglycerols.

We reported previously that sulfolipids in the sulfoquinovosylacylglycerol class from a fern and an alga are potent inhibitors of DNA polymerase alpha and beta and potent anti-neoplastic agents. In developing a procedure for chemical synthesis of sulfolipids, we synthesized many derivatives and stereoisomers of sulfoquinovosylmonoacylglycerol (SQMG) / sulfoquinovosyldiacylglycerol (SQDG). Some of these molecules were stronger inhibitors than the SQMG / SQDG originally reported as natural compounds. In this study, we examined the structure-inhibitory function relationship of synthetic SQMG / SQDG and its relationship to cytotoxic activity. The inhibitory effect is probably mainly dependent on the fatty acid effect, which we reported previously, although each of the SQMG / SQDG was a much stronger inhibitor than the fatty acid alone that was present in the SQMG / SQDG. The inhibitory effect could be influenced by the chain size of fatty acids in the SQMG / SQDG. The sulfate moiety in the quinovose was also important for the inhibition. Lineweaver-Burk plots of SQMG / SQDG indicated that DNA polymerase alpha was non-competitively inhibited, but the SQMG / SQDG were effective as antagonists of both template-primer DNA-binding and nucleotide substrate-binding of DNA polymerase beta. The SQMG had an cytotoxic effect, but the SQDG tested did not. The SQDG might not be able to penetrate into cells. Based on these results, we discuss the molecular action of SQMG / SQDG and propose drug design strategies for developing new anti-neoplastic agents.

Antineoplastic Agents↗
PubMed2000

Sgs1 helicase activity is required for mitotic but apparently not for meiotic functions.

The SGS1 gene of Saccharomyces cerevisiae is a homologue for the Bloom's syndrome and Werner's syndrome genes. The disruption of the SGS1 gene resulted in very poor sporulation, and the majority of the cells were arrested at the mononucleated stage. The recombination frequency measured by a return-to-growth assay was reduced considerably in sgs1 disruptants. However, double-strand break formation, which is a key event in the initiation of meiotic DNA recombination, occurred; crossover and noncrossover products were observed in the disruptants, although the amounts of these products were slightly decreased compared with those in wild-type cells. The spores produced by sgs1 disruptants showed relatively high viability. The sgs1 spo13 double disruptants sporulated poorly, like the sgs1 disruptants, but spore viability was reduced much more than with either sgs1 or spo13 single disruptants. Disruption of the RED1 or RAD17 gene partially alleviated the poor-sporulation phenotype of sgs1 disruptants, indicating that portions of the population of sgs1 disruptants are blocked by the meiotic checkpoint. The poor sporulation of sgs1 disruptants was complemented with a mutated SGS1 gene encoding a protein lacking DNA helicase activity; however, the mutated gene could suppress neither the sensitivity of sgs1 disruptants to methyl methanesulfonate and hydroxyurea nor the mitotic hyperrecombination phenotype of sgs1 disruptants.

Adenosine Triphosphatases↗
PubMed2000

A rapid and simple photometric assay for quantification of eosinophil chemotaxis.

Various methods have been devised to assay eosinophil chemotaxis. In this review, we introduced a rapid and sensitive eosinophil chemotactic assay system based on eosinophil peroxidase (EPO) determination. Eosinophils were semipurified by dextran sedimentation followed by Percoll gradient centrifugation. Eosinophil migration was measured by the Boyden blind-well chamber technique using a 96-well multiwell chamber and polycarbonate membrane filter. The number of migrated eosinophils was assessed by determination of the EPO activity of drop-off cells, and photometric measurement was performed with a microtiter plate reader. The contribution of neutrophil peroxidase to the assay is negligible, and the assay is sensitive enough to detect 200 eosinophils. The method is both less tedious and less laborious than conventional manual methods, and it allows a large number of samples to be analyzed within 4 h. When eosinophils were exposed to 15 chemokines and their migration was assayed using this method, we found that only CC chemokine receptor 3 ligands, such as eotaxin, induced significant eosinophil migration.

Chemotaxis, Leukocyte↗
PubMed2000

Induction of apoptosis in bronchial eosinophils: beneficial or harmful?

BACKGROUND: Prominent eosinophil infiltration takes place in asthmatic bronchi, and damages bronchial epithelial cells. AIM: This study was designed to investigate whether induction of apoptosis in infiltrated cells in the airways is beneficial or harmful. METHODS: A/J mice, which are genetically predisposed to be hyperresponsive to acetylcholine, were immunized with ovalbumin (OA) and alum. Thereafter, they were subjected to a 2-week regimen of OA inhalation, during which they were also administered either hamster anti-mouse Fas monoclonal antibody or hamster IgG (sham control) intranasally. Pulmonary function was then analyzed using whole-body plethysmography. RESULTS: Inhalation of OA increased both airway responsiveness to acetylcholine and infiltration of eosinophils. Administration of anti-Fas antibody induced apoptosis in the infiltrating eosinophils and abolished the increase in airway responsiveness to acetylcholine. CONCLUSION: Induction of apoptosis in eosinophils infiltrating asthmatic bronchi has a beneficial effect on airway hyperresponsiveness.

Acetylcholine↗
PubMed2000

Clinical significance of simultaneous measurement of reticulated platelets and large platelets in idiopathic thrombocytopenic purpura.

Frequencies of reticulated platelets (RP) and large platelets (LP) among circulating platelets can now be simultaneously determined using the R-3000 automated reticulocyte counter (Sysmex, Kobe, Japan) equipped with special software. We measured frequencies of RP and LP in patients with idiopathic thrombocytopenic purpura (ITP. acute type n = 5; chronic type n = 39), and healthy normal controls (n = 20). In ITP patients, the platelet-associated IgG (PAIgG) level was also determined. Both RP and LP were significantly higher in chronic ITP patients than those in normal volunteers, and interestingly, the LP in acute ITP was significantly lower than that in chronic ITP although there was no significant difference in RP between acute and chronic ITP. Furthermore, we analyzed the changes in both RP and LP during the clinical course of ITP to monitor the therapeutic effect in 2 patients. An elevation of RP with a steep slope prior to a decrease in the platelet count level was observed. The RP significantly correlated with the PAIgG level. Simultaneous measurement of RP and LP may be helpful for the diagnosis of chronic ITP, for the differentiation of acute from chronic type and for the control of the efficacy of management in ITP, since RP seems to reflect the disease activity of ITP.

Female↗
PubMed2000

Retinoidal pyrimidinecarboxylic acids. Unexpected diaza-substituent effects in retinobenzoic acids.

Several pyridine- and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]pyri dine-3-carboxylic acid (2b) and 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]py ridine-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)a mino]pyrimidine-5-carboxylic acid (PA013, 10e) is most active retinoid synergist in HL-60 assay.

Animals↗
PubMed2000

Molecular cloning and sequence analysis of an endoinulinase gene from Penicillium sp. strain TN-88.

A genomic DNA segment and cDNAs encoding an extracellular endoinulinase of Penicillium sp. strain TN-88 were cloned and sequenced. Southern blot analysis indicated that the endoinulinase gene (inuC) was present as a single copy in the genome. An open reading frame, consisting of 1,545 bp, was not interrupted by introns, and it encoded a 25 amino acid signal peptide and a 490 amino acid mature protein. The mature protein contained three Cys residues and ten potential N-linked glycosylation sites. Three distinct transcriptional start points were observed at positions -242 (A), -215 (A), and -75 (C) from the start codon. The 5'-noncoding region had a putative TATA box at position -120 (TATATATA) and two contiguous CAAT sequences at -159 to -151. The deduced amino acid sequence showed 72 and 85% identities with those of Aspergillus niger and Penicillium purpurogenum endoinulinase genes, respectively. A neighbor-joining tree showed that fungal endoinulinases form a distinct cluster from other members of the beta-fructofuranosidase superfamily and that they are more closely related to bacterial levanases than to a fungal fructosyltransferase, yeast invertases, or a yeast exoinulinase.

3' Untranslated Regions↗
PubMed2000

Thymic hyperplasia as a source of ectopic ACTH production.

A 26 year-old man with suspected Cushing's disease underwent transsphenoidal exploration of the pituitary without any evidence of microadenoma or hyperplasia. Progressive hypercortisolism necessitated bilateral adrenalectomy. Postoperatively, skin pigmentation gradually developed with a marked elevation of plasma ACTH levels, and CT scanning uncovered a thymic mass. Following removal of the thymic mass, skin pigmentation disappeared and plasma ACTH levels fell to normal. The excised mass was found to be a benign thymic hyperplasia without epithelial or carcinoid tumor cells. However, gel chromatography showed that the thymic tissue extract contained high ACTH content comparable to that of ectopic ACTH-producing tumors with a major component corresponding to ACTH(1-39). Northern blot analysis and in situ hybridization revealed the expression of proopiomelanocortin transcripts in lymphocytes of thymic hyperplasia. This report suggests that lymphocytes in thymic hyperplasia are the most likely site of deregulated ACTH expression causing ectopic ACTH syndrome.

ACTH Syndrome, Ectopic↗
PubMed2000

A diffuse alveolar hemorrhage in a human T-lymphotropic virus type I carrier with acute cerebellar ataxia and interstitial pneumonitis: an autopsy case report.

A 76-year-old HTLV-I-positive male with acute cerebellar ataxia was suffering from dyspnea on exertion. Chest CT suggested interstitial pneumonitis. Methylprednisolone pulse therapy improved his symptoms and chest CT findings. Twelve months after discharge, when the prednisolone dose was tapered to 5 mg every other day, his lung lesion recurred. The lesion responded initially to steroid therapy. However, hypoxemia intractable to steroid pulse therapy developed and the patient died of respiratory failure. The autopsy revealed diffuse alveolar hemorrhage with no finding of vasculitis. This is the first case report of diffuse alveolar hemorrhage in an HTLV-I carrier.

Acute Disease↗
PubMed2000

Polypropylene mesh substitute for the fascial defect after using for the dural repair--technical note.

Use of the anterior sheath of the rectus abdominis muscle (anterior sheath) as a dural substitute and patching of the large defect of the anterior sheath with polypropylene mesh are described. Five patients were treated using the anterior sheath and the mesh. No postoperative complications such as cerebrospinal fluid leakage, infection, or abdominal wall hernia occurred. The mesh is useful as a patch for the sheath defect.

Abdominal Muscles↗
PubMed2000

Clinical evaluation of a radioimmunoprecipitation assay for IA-2 antibody and comparison of GAD antibody in type 1 diabetes mellitus.

We evaluated a insulinoma-associated protein (IA-2) antibody assay kit using 125I-labelled recombinant IA-2. IA-2 antibodies were present in patients with early-onset type 1 diabetes mellitus (DM) at frequencies of 74%, 67%, 57%, and 50% for respective periods <1 year, 1 < or =years<2, 2< or =years<3, and 3< or =years<4 after onset. IA-2 antibody frequency was low throughout the DM course as compared with glutamic acid decarboxylase (GAD) antibody frequency. No one had IA-2 antibody, but 29% still had positive GAD antibody titers after 11 years. Of the patients with 0<years<7 duration, 42% had IA-2 Ab+/GAD Ab+, 9% IA-2 Ab+/GAD Ab-, and 24% IA-2 Ab-/GAD Ab+. Prevalence of IA-2 and GAD antibody in 1243 patients with type 2 DM were 1.5% and 3.1%, respectively, and 1.1% had both. This new IA-2 antibody kit is easy to use and provides a specific, sensitive method for making routine assays. Furthermore, the combined analysis of GAD antibody provides high detection of type 1 DM.

Adolescent↗