[A case of perforative peritonitis due to ischemic colitis associated with use of oral contraceptives].
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Colitis, Ischemic↗
Biomedical subjects
Y Ozeki
Publications and source records attributed to Y Ozeki.
Cooperative alkylation by duocarmycin A-distamycin A heterodimer.
Duo A (Duo) normally alkylates adenine N3 at the 3' end of A + T-rich sequence in DNA. The addition of another minor groove binder, dist A (Dist), dramatically modulate the site of DNA alkylation by Duo with great acceleration of the reaction rate. In order to examine the mode of alkylation, the kinetics of the reaction under various conditions were examined. Based on the simulation of experimental data, a new reaction pathway was proposed.
Alkylating Agents↗
An N-linked high-mannose type oligosaccharide, expressed at the major outer membrane protein of Chlamydia trachomatis, mediates attachment and infectivity of the microorganism to HeLa cells.
The structure of the carbohydrate of the 40-kD major outer membrane component of Chlamydia trachomatis and its role in defining infectivity of the organism were investigated. The oligosaccharides were released from the glycoprotein by N-glycanase digestion, coupled to a 2-aminopyridyl residue, and subjected to two-dimensional sugar mapping technique. The major fractions consisted of "high-mannose type" oligosaccharides containing 8-9 mannose residues. Bi- and tri-antennary "complex type" oligosaccharides having terminal galactose were detected as minor components. These oligosaccharides were N-linked and contained no sialic acid. This structural profile is consistent with our previous characterization based on lectin-binding and glycosidase digestion. Functional specificity of identified chlamydial oligosaccharides was analyzed using glycopeptides fractionated from ovalbumin and structurally defined oligosaccharides from other sources. The glycopeptide fraction having high-mannose type oligosaccharide, as compared to those having complex or hybrid-type, showed a stronger inhibitory effect on attachment and infectivity of chlamydial organisms to HeLa cells. Among high-mannose type oligosaccharides, the strongest inhibition was observed with mannose 8 as compared with mannose 6, 7, or 9. These results indicate that a specific high-mannose type oligosaccharide linked to the major outer membrane protein of C. trachomatis mediates attachment and infectivity of the organism to HeLa cells.
Amidohydrolases↗
Purification and characterization of bitiscetin, a novel von Willebrand factor modulator protein from Bitis arietans snake venom.
We have screened 20 snake venoms and purified a novel snake venom protein, named bitiscetin, from Bitis arietans venom that specifically binds to human von Willebrand factor (vWF) and induces platelet agglutination. Bitiscetin showed a heterodimeric structure composed of disulfide-linked alpha (16kDa) and beta (13kDa) subunits on SDS-PAGE and showed a basic nature with pI value of 9.1, in contrast to botrocetin (pI 4.6), a vWF modulator isolated from another snake (Bothrops jararaca) venom. Bitiscetin-induced platelet agglutination was dependent on vWF and platelet membrane glycoprotein (GP) Ib, but not on Ca2+ and GPIIb/IIIa. vWF bound to bitiscetin but not to botrocetin electroblotted to a PVDF membrane after SDS-PAGE and this binding was diminished after reduction of disulfide bonds of bitiscetin. Bitiscetin did not cross-react to anti-botrocetin monoclonal antibodies. These results suggest that bitiscetin directly interacts with vWF and requires the protein conformation for its interaction as well as botrocetin, but its interaction manner with vWF appears to be different from that of botrocetin.
Amino Acid Sequence↗
Immunohistochemical analysis of the nm23 gene product (NDP kinase) expression in astrocytic neoplasms.
The expression levels of nm23-H1 have been reported to correlate with the metastatic potential of some tumours. We have treated a child with a rare case of astrocytoma with diffuse osteoblastic metastases. We therefore decided to examine the expression of the nm23 gene product in 24 gliomas in order to clarify the association of its expression with the clinical features of the disease. A polyclonal antibody against a GST/nm23-H1 fusion protein was raised in rabbits. Twenty-four specimens, including 5 recurrent gliomas and one extraneural metastasis, were obtained from 19 patients treated surgically between 1990 and 1993 in our hospital. Immunohistochemical staining was performed on paraffin sections using an avidin-biotinyl peroxidase complex method. Of the 24 astrocytic neoplasms, 3 (12.5%) specimens from one patient with diffuse bony metastases stained intensely with nm23-H1. Two specimens obtained from glioblastoma multiforme patients stained weakly. The other 19 specimens were negative for nm23-H1 expression. Little or no nm23 expression was observed in adjacent nontumourous cerebral tissues. The results suggest that high levels of nm23 expression might correlate with extraneural metastatic potential in astrocytic neoplasms.
Adolescent↗
P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo.
We examined whether the increased expression of P-glycoprotein (P-gp) encoded by the human multidrug resistance gene MDR1 is related to the acquired multidrug resistance of lung cancer in vivo. We estimated the chemosensitivity of lung cancer xenografts (LC-6, adenocarcinoma; Lu-24, small-cell cancer) by calculation of relative tumour growth (T/C%, treated/control) in vivo, based on statistical significance determined by the Mann-Whitney U test (P < 0.01, one-sided). MDR1 gene expression levels were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) assay. P-gp production and P-gp localisation were examined by Western blotting and by immunohistochemical analysis respectively. LC-6 and Lu-24 were initially sensitive to both vincristine (VCR, 1.6 mg kg-1: LC-6, 45%; Lu-24, 39%) and doxorubicin (DOX, 12 mg kg-1: LC-6, 26%; Lu-24, 27%) in vivo. VCR-resistant variants (LC-6R, 66% and Lu-24R, 68%) selected with VCR (0.4 mg kg-1, x 9) significantly acquired cross-resistance to DOX (LC-6R, 55% and Lu-24R, 55% respectively). RT-PCR assay showed increased levels of MDR1 expression in LC-6R and Lu-24R with stable MDR1 expression levels. P-gp expression levels were elevated, and the percentage of P-gp-positive tumour cells increased in both LC-6R and Lu-24R. These results suggest that P-gp/MDR1 overexpression is related to acquired multidrug resistance in lung cancer in vivo.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Spontaneous complete necrosis of hepatocellular carcinoma.
We report a 69-yr-old female with a liver mass which, when surgically resected, was believed to be the spontaneous complete necrosis of hepatocellular carcinoma. The preoperative level of alpha-fetoprotein was high at 1050 ng/ml, and the mass was grossly an encapsulated nodular lesion with septa. Histologically, no viable tumor cells were demonstrated. The alpha-fetoprotein level decreased to a normal range. The postoperative course was uneventful, and the patient is alive and well 1 yr after surgery.
Aged↗
[Metaplastic cholecystitis].
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Cholecystitis↗
[A case of catamenial pneumothorax with elevated level of serum CA 125].
A 40-year old woman had experienced repeated spontaneous pneumothorax on the right side at the beginning of each menstrual period for one year. The level of serum CA125 was high at 60 ng/ml. Right thoracotomy revealed the presence of multiple darkly-pigmented spots and several pinhole like perforations near the central tendon of the diaphragm. The partial resection of the diaphragm was done, endometrial tissues were detected histologically. Tha patient has been asymptomatic after operation and the level of serum CA125 is normal.
Adult↗
Developmental expression of D-galactoside-binding lectin in sea urchin (Anthocidaris crassispina) eggs.
The spatial and temporal expression of a sea urchin (Anthocidaris crassispina) egg lectin (SUEL) during early embryogenesis was studied using antiserum raised against SUEL. Western blotting analysis revealed the presence of SUEL in all stages so far examined, from unfertilized eggs to gastrula stage embryos. Immunofluorescence and immunoelectron microscopic observation showed that SUEL was stored in small electron-dense granules which migrated to the cortex within 10 min after fertilization. SUEL was localized in the cortical cytoplasm of the blastomere during cleavage stages and subsequently migrated to the outer surface of the embryo, including the invaginated portion of the gastrula. Immunoelectron microscopic study indicated that SUEL was deposited in the hyaline layer at least at the mid gastrula stage. Migration of SUEL to the cortex was significantly reduced by treatment with cytochalasin B, suggesting that actin filaments play an important role in this translocation. Exogenously added SUEL was adsorbed at the surface of unfertilized eggs and hatched embryos, but not to embryos with fertilization membrane. Lactose inhibited this adsorption, suggesting the presence of an endogenous glycoligand(s) specific for SUEL on the surface of unfertilized eggs and in the hyaline layer. We conclude that SUEL is secreted at a certain stage of embryogenesis and specifically adsorbed to the hyaline layer. Temporal changes in extraembryonic matrices caused by SUEL seem to play an important role in developmental morphogenesis.
Actin Cytoskeleton↗
Binding of human IgM from a rheumatoid factor to IgG of 12 animal species.
The binding of IgM from a rheumatoid factor (RF-IgM) to IgG from 12 animal species was analyzed by an ELISA system. The RF-IgM bound various animal IgG with dissimilar affinities. The binding of RF-IgM to animal IgG was inhibited by addition of protein A, which binds some animal IgG by recognizing the junctional site on CH2-CH3 domains in the Fc region. As previously reported, no significant correlation was observed between the binding of RF-IgM to IgG and the content of galactose-free oligosaccharides, which is increased in IgG of rheumatoid arthritis patients or autoimmune mice. We suggest that the crucial epitope of IgG for RF-IgM binding is not the oligosaccharide structure generated specifically in IgG of autoimmune diseases but that RF-IgM may recognize a certain protein conformation of a region in IgG near the binding site of protein A.
Animals↗
Metabolism of clomipramine in a Japanese psychiatric population: hydroxylation, desmethylation, and glucuronidation.
We measured the concentrations of clomipramine and its metabolites, N-desmethylclomipramine, 8-hydroxy-N-desmethylclomipramine, 8-hydroxyclomipramine by high-performance liquid chromatography in 108 Japanese psychiatric patients receiving clomipramine hydrochloride PO. The concentrations of the glucuronide conjugates of 8-hydroxyclomipramine and 8-hydroxy-N-desmethylclomipramine were assayed via enzymatic hydrolysis. Although there were large interindividual variations of concentrations of parent, intermediate metabolic compounds, and glucuronide conjugates, significant positive correlations were observed between these drug concentrations and daily doses of clomipramine hydrochloride (mg/kg body weight). Although the metabolic ratios for desmethylation, hydroxylation, and glucuronidation that were calculated from steady-state drug concentrations varied substantially with 36-, 14-, and 28-fold interindividual variations, respectively, apparent poor desmethylators, poor hydroxylators, or poor glucuronidators were not found.
Adolescent↗
Extended left hepatic trisegmentectomy with resection of main right hepatic vein and preservation of middle and inferior right hepatic veins.
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Aged↗
Expression of the multidrug resistance-associated protein (MRP) gene in non-small-cell lung cancer.
We examined the levels of expression of the multidrug resistance-associated protein (MRP) gene quantified by Northern blot analysis in comparison with those of the MDR1 gene determined by reverse transcription-polymerase chain reaction (RT-PCR) in 104 non-small-cell lung cancer (NSCLC) specimens [59 adenocarcinoma (Ad), 40 squamous cell carcinoma (Sq), four large cell carcinoma (La) and one adeno-squamous carcinoma (AdSq)]. Thirty-three (31.7%) of the 104 NSCLC expressed the MRP gene at various levels. The NSCLC showing high (++) levels of MRP gene expression (19 out of 33, 57.6%) were predominantly squamous cell carcinomas (Ad, 5; Sq, 13; La, 1) (P < 0.05). Six of the eight NSCLCs expressing high levels of MRP mRNA and no MDR1 (MRP ++, MDR1-) were squamous cell carcinomas. Sixty-one of the 104 NSCLC patients received chemotherapy with MRP-related anti-cancer drugs [vindesine (VDS) and etoposide (VP-16)]. Twenty-three patients (37.7%) with tumour expressing high or moderate levels of MRP showed significantly worse prognoses than those with non- or low-MRP-expressing tumours (P < 0.05). These results suggest that the level of MRP gene expression is related to the histopathology and prognosis of NSCLC.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Tissue fibronectin is an endogenous ligand for galectin-1.
A 14K beta-galactoside-binding lectin (galectin-1) is present in many animal tissues. In a search for endogenous ligands, we surveyed galectin-1-binding proteins in human placenta. Extract of human placenta with 2 M urea was applied to a Sepharose 4B column conjugated with galectin-1 purified from frog (Rana catesbeiana) eggs. Two major proteins eluted with 100 mM lactose from the column-bound fraction showed apparent molecular masses of 220 and 180 kDa on SDS-PAGE under reducing conditions. Western blotting analysis using monoclonal antibodies indicated that these proteins were fibronectin and laminin, respectively. Most placental and amniotic fibronectins bound strongly to the column, whereas almost all plasma fibronectin passed through the column. The galectin-1, fibronectin and laminin were immunohistochemically shown to be co-localized in the extracellular matrix of placental tissue. In a cell attachment assay, rhabdosarcoma cells adhered to a plate coated with placental fibronectin, even in the presence of GRGDS peptide, if galectin-1 were also present. This adhesive effect of galectin-1 was inhibited by lactose. These results indicate that tissue fibronectin, as well as laminin, serve as endogenous ligands for galectin-1, suggesting that galectin-1 may play a role in assembly of the extracellular matrix, or in the control of cell adhesion based on lectin-extracellular matrix interaction.
Animals↗
Interindividual variations of desmethylation and hydroxylation of amitriptyline in a Japanese psychiatric population.
We measured the concentrations in plasma of amitriptyline and its metabolites, nortriptyline and geometric isomers of 10-hydroxynortriptyline and 10-hydroxyamitriptyline, in 73 Japanese psychiatric patients receiving amitriptyline hydrochloride (Tryptanol; Banyu Pharmaceutical Co. Ltd., Tokyo, Japan) by high-performance liquid chromatography. Although there were large interindividual variations of total drug concentrations and concentrations of parent or intermediate metabolic compounds in plasma, significant positive correlations were observed between these drug concentrations and daily doses of amitriptyline hydrochloride (milligrams per kilogram of body weight). The metabolic ratios for both hydroxylation and desmethylation varied substantially with approximately 8- to 19-fold interindividual variations. Frequency distribution histograms and probit analyses of these parameters identified neither definite poor hydroxylators nor poor desmethylators of amitriptyline.
Adult↗
Stenosis enhances role of platelets in growth of regional thrombus and intimal wall thickening in rat carotid arteries.
The authors present the results of a study in which stenosis was induced, resulting in either thrombus or intimal wall thickening, in rat carotid arteries. At > or = 75% stenosis in mildly denuded arteries, an acute and occlusive thrombus formation was induced, but the thrombus was significantly reduced in thrombocytopenia. Thrombus formation near the site of stenosis decreased with decreasing degree of stenosis, whereas the percent formation in the distal region (percent total thrombus) increased. Numerous mural platelet microthrombi were noted at the distal region of the stenosed arteries. After chronic 50% stenosis of the carotid artery for 2 weeks, significant intimal thickening was observed, without any occlusive thrombus formation. The combination with mild denudation was critical in eliciting the effect of stenosis. The magnitude of intimal growth in the stenosed artery was marked by day 6 and plateaued thereafter, whereas it was slight in nonstenosed arteries. The 5-bromodeoxyuridine index of the cells of the medial layer at day 3 was significantly increased by the stenosis, and the effect was reversed in thrombocytopenia. Complete reendothelialization of the intimal surface was observed by 7 to 10 days after surgery in the stenosed arteries. These findings suggest that the introduction of stenosis in these arteries enhances the interaction of platelets with the damaged arterial walls under abnormal fluid shear and that this enhancement leads to acute and occlusive thrombus formation associated with more marked stenosis as well as to sustained increase of intimal wall thickness in less marked stenosis.
Animals↗
Synthesis of 2(1H)-quinolinone derivatives and their inhibitory activity on the release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE) from platelets.
A search for potent inhibitors of release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE), which plays an important role in the pathogenesis of various circulatory disorders and arteriosclerosis, led us to 6-[4-(1-cyclohexyl-5-tetrazolyl)butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and 2(1H)-quinolinone derivatives having an azole group in the side chain. Many 2(1H)-quinolinone derivatives were synthesized and tested in vitro for the inhibitory activity in human platelets. 3,4-Dihydro-6-[3-(1-o-tolylimidazol-2-yl)sulfinylpropoxy]-2( 1H)-quinolinone (5k) was found to be one of the most potent inhibitors of 12-HETE release, being more potent than esculetin. In addition, the sulfoxide 5k showed in vivo inhibitory activity on platelet adhesion in rats. Since 5k is racemic, the enantiomers were prepared and their potencies were compared in vitro and in vivo. (S)-(+)-5k had the best pharmacological profile and was selected as a candidate drug for further development. The structure-activity relationships are discussed.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗