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Biomedical subjects

K Akiba

Publications and source records attributed to K Akiba.

At least 19 recordsLinked to original sources

Synthesis, structure, electrochemistry, and spectroelectrochemistry of hypervalent phosphorus(V) octaethylporphyrins and theoretical analysis of the nature of the PO bond in P(OEP)(CH(2)CH(3))(O).

A variety of phosphorus(V) octaethylporphyrin derivatives of the type [P(OEP)(X)(Y)](+)Z(-) (OEP: octaethylporphyrin) (X = CH(3), CH(2)CH(3), C(6)H(5), F; Y = CH(3), CH(2)CH(3), OH, OCH(3), OCH(2)CH(3), On-Pr, Oi-Pr, Osec-Bu, NHBu, NEt(2), Cl, F, O(-); Z = ClO(4), PF(6)) were prepared. X-ray crystallographic analysis of eleven compounds reveals that the degree of ruffling of the porphyrin core becomes greater and the average P-N bond distance becomes shorter as the axial ligands become more electronegative. Therefore, the electronic effect of the axial substituents plays a major role in determining the degree of ruffling although the steric effect of the substituents plays some role. A comparison of the (1)H NMR chemical shifts for the series of [P(OEP)(CH(2)CH(3))(Y)](+)Z(-) complexes with those of the corresponding arsenic porphyrins, which possess a planar core, indicates a much smaller ring current effect of the porphyrin core in the severely ruffled phosphorus porphyrins. The electrochemistry, spectroelectrochemistry and ESR spectroscopy of the singly reduced compounds are also discussed. The OH protons of [P(OEP)(X)(OH)](+) are acidic enough to generate P(OEP)(X)(O) by treatment with aq dilute NaOH. X-ray analysis of P(OEP)(CH(2)CH(3))(O) reveals that the PO bond length is very short (1.475(7) A) and is comparable to that in triphenylphosphine oxide (1.483 A). The features of the quite unique hexacoordinate hypervalent compounds are investigated by density functional calculation of a model (Por)P(CH(2)CH(3))(O) and (Por)P(F)(O) (Por: unsubstituted porphyrin).

Journal Article↗

Highly selective one-pot synthesis of spirophosphoranes exhibiting reversed apicophilicity by oxidation of dianions generated from P-H spirophosphorane.

[see reaction]. Mild and highly selective one-pot procedures for obtaining phosphoranes that exhibit reversed (O-cis) apicophilicity are described. On the basis of the procedures, O-cis phosphorane bearing an aryl group (R = 2,4,6-tri-i-propylphenyl) could be isolated for the first time; the procedure is also applicable for alkyl derivatives. Particularly effective was the use of I2 as an oxidizing reagent.

Journal Article↗

Affinity chromatography for purification of two urokinases from human urine.

A new affinity chromatography (hydrophobic-mediated affinity chromatography), which was characterized by the matrix having both affinity site to urokinase and hydrophobic site, was established for the purification of urokinase from human urine. The hydrophobic affinity matrix (tentatively named PAS in the text) was prepared by immobilizing 6-aminocaproic acid on Sepharose CL-6B, followed by a coupling p-aminobenzamidine to a part of the hydrophobic site on the matrix. The PAS matrix was applied to the purification of urokinase from human urine, and high- and low-molecular weight pure urokinases were efficiently obtained in high yield by the present method.

Chromatography, Affinity↗

Matrix metalloproteinase activity is enhanced during corneal wound repair in high glucose condition.

PURPOSE: (1) To investigate the effect of elevated extracellular glucose on migration, proliferation, and the activity of matrix metalloproteinases (MMPs) of SV40-transformed human corneal epithelial cells (HCEC). (2) To examine MMP activity in wounded corneal epithelium in diabetic rats. METHODS: HCEC were cultured in media containing 5.5 mM or 31.2 mM D-glucose, or in a combination of 5.5 mM D-glucose and 25.7 mM D-mannitol on fibronectin/collagen I-coated 48-well plates. After reaching confluence (day 0), cells in the central part of the plate were wounded and the residual cells were cultured for 3 days. Migration and proliferation were evaluated by assessing the increasing amount of area covered by cells, and the day-3 to day-0 ratio of DNA levels, respectively. To determine MMP activity, cells were reacted with synthetic fluorogenic substrates specific to MMPs 1, 2, 3, 7, 9, and MMP activity was determined by a fluorometric kinetic assay. Diabetic rats were induced by streptozotocin injection. Corneal epithelium was scraped from limbus-to-limbus and allowed to heal. Normal rats were treated similarly to serve as controls. Healing epithelium was collected 24 hours later, and gelatin zymography was performed. RESULTS: In the cell culture study, migration in 31.2 mM glucose was significantly slower than that in 5.5 mM, but proliferation in each concentration was similar. The osmotic effect of D-mannitol did not alter migration or proliferation. MMP activity in 31.2 mM was significantly higher than that in 5.5 mM. Zymography revealed enhanced activity of pro and active MMP-9 in healing corneal epithelium in diabetic rats. CONCLUSIONS: MMP activity was enhanced in healing corneal epithelium, both in in vitro and in vivo diabetic models, suggesting its involvement in diabetic keratopathy.

Animals↗

Intermittent jaundice in patients with acute leukaemia: a common mutation of the bilirubin uridine-diphosphate glucuronosyltransferase gene among Asians.

The Gly71Arg mutation of the hepatic bilirubin UDP glucuronosyl-transferase (B-UGT) gene associated with Gilbert syndrome prevails among Japanese and its gene frequency is 0.13. Among 20 patients with acute leukaemia, 4 patients showed intermittent unconjugated hyperbilirubinaemia during the course of combined chemotherapy. The Gly71Arg mutation was detected in all 4 patients with hyperbilirubinaemia, but was not found in 16 patients without hyperbilirubinaemia. Two of them were heterozygotes and one was a homozygote for the Gly71Arg mutation, and the other was a compound heterozygote of the Gly71Arg mutation and TA insertion mutation in the TATA box of the B-UGT gene. In addition to the complications leading to hyperbilirubinaemia, including liver damage due to drugs, viral infections or tumour cell infiltrations and alloimmune haemolysis, carrier status for the Gly71Arg mutation should be considered in a patient with leukaemia showing intermittent hyperbilirubinaemia during the course of chemotherapy, especially among Japanese, Koreans and Chinese owing to its prevalence in those populations.

Acute Disease↗

Muscular dystrophy associated with extra-abdominal desmoid tumor showing aberrant chromosome 1 [46,XX,add(1)(p36)].

We report on a 2-year-old girl with probable limb-girdle muscular dystrophy associated with an extra-abdominal desmoid tumor of the right mandible. This association is previously undescribed. The tumor was totally removed. Cytogenetic analysis of the tumor showed a clonal karyotypic abnormality: 46,XX,add(1)(p36) in 3 of 20 cells analyzed. Since an association of a neoplasm with limb-girdle muscular dystrophy has previously been reported in 3 cases, the two abnormalities are likely related causally. The chromosome abnormality in our patient may play a role in the occurrence of her desmoid tumor.

Child, Preschool↗

CD48 expression on leukocytes in infectious diseases: flow cytometric analysis of surface antigen.

BACKGROUND: The function of CD48, one of the pan leukocyte cell surface antigens, is not yet well understood. CD48 was recently shown to enhance the CD40-mediated activating signal to B lymphocytes. As CD48 is one of the activation antigens of monocytes, neutrophils and lymphocytes, a change of its expression on the cells could be expected in infectious diseases. METHODS AND RESULTS: Leukocytes from 27 healthy controls and 97 patients with various infectious diseases were stained with anti CD48 antibody and analyzed by flow cytometry. On monocytes and neutrophils, the CD48 expression was increased in all of the patients with varicella, measles, rubella, infectious mononucleosis, streptococcus tonsillitis, sepsis and appendicitis. On lymphocytes, a significant increase of CD48 was also detected in the patients with the same diseases, except those with sepsis or appendicitis. The normalization of increased CD48 expression was confirmed on monocytes at the convalescent phase. CONCLUSION: These data suggest that CD48 expression on leukocytes reflects the disease activity of infectious diseases, especially of viral infections.

Adolescent↗

Defective signal transduction through the thromboxane A2 receptor in a patient with a mild bleeding disorder: deficiency of the inositol 1,4,5-triphosphate formation despite normal G-protein activation.

We describe an 11-year-old girl with a mild bleeding disorder since early childhood. The disorder was characterized by a prolonged bleeding time, and the patient's platelets showed defective aggregation responses to thromboxane A2 (TXA2) mimetic U46619 and arachidonic acid. In contrast, the platelets showed normal responses to thrombin and Ca ionophore A23187. When the platelet TXA2 receptor was examined with the [3H]-labeled TXA2 agonist U46619, the equilibrium dissociation rate constants (kd) and the maximal concentration of binding sites (Bmax) of the patient's platelets were within normal ranges. Normal GTPase activity was also induced in the patient's platelets by stimulation with U46619, however, inositol 1,4,5-triphosphate (IP3) formation was not induced by U46619. These results suggests that the patient's platelets had a defect in phospholipase C activation beyond TXA2 receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Severe hypertension and cardiac failure associated with neuroblastoma: a case report.

The authors report on 3-year-old-girl with neuroblastoma complicated by severe hypertension and cardiac failure. She had cardiomegaly and pleural and pericardial effusions. Echocardiogram showed left ventricular hypertrophy and decrease of the left ventricular ejection fraction to 0.36 (normal > .40). Abdominal computed tomographic scan indicated a 7 x 7-cm tumor in the left suprarenal area. There was a marked increase in catecholamines and metabolites in her body fluids. After hypertension was controlled with doxazosin (a long-acting alpha 1 adrenergic blocker), her cardiac function gradually improved. A tumor was surgically removed and diagnosed as a poorly differentiated ganglioneuroblastoma. Preoperative differentiation between neuroblastoma and pheochromocytoma was not possible on the basis of catecholamine analysis or imaging studies including computed tomography scan and magnetic resonance imaging. It is important to control hypertension quickly in the patients with catecholamine-induced cardiomyopathy to facilitate surgical intervention for diagnosis and treatment.

Adrenergic alpha-Antagonists↗

Increased expression of CD48 on neutrophils activated in childhood patients with aplastic anemia.

Activation-associated antigens such as CD11b, CD14 and CD64 of neutrophils have been reported. Although CD48 is an activation antigen of lymphocytes and monocytes, whether it is an activation antigen of neutrophils has not previously been examined. Herein, using FACS analysis, we examined the expression of surface CD48 on neutrophils activated in vivo by G-CSF administered for the treatment of idiopathic aplastic anemia. CD48 expression was increased 24 h after the initial G-CSF infusion and peaked within 1 week. Within a few days after discontinuation of G-CSF administration, it returned to the pretreatment level. This indicates that CD48 is an activation antigen of neutrophils.

Adolescent↗

Gender-related differences in cocaine toxicity in the rat.

To test our hypotheses that gender-related differences in cocaine toxicity exist in the rat, cocaine (2 mg/kg/min) was infused intravenously in chronically catheterized male and ovariectomized or intact female rats until the onset of circulatory collapse. Sequential manifestations of cocaine toxicity from mild central nervous stimulation to fatal cardiovascular collapse were observed. Arterial blood was withdrawn at the onset of the toxic signs or symptoms for determination of cocaine concentrations. Dosages and plasma concentrations of cocaine required to produce cardiovascular toxic manifestations were significantly lower in male and ovariectomized rats than in intact females. Plasma cholinesterase activity was lowest in the male animals and highest in intact females. These data suggest that systemic toxicity of cocaine is enhanced in male rats, because lower doses and plasma concentrations are required to induce toxic signs and symptoms.

Akathisia, Drug-Induced↗

Hypozincemia during fever may trigger febrile convulsion.

Febrile convulsions are generally thought to be induced by metabolic changes during the rise-phase of body temperature. The mechanism by which convulsions are induced, however, is not fully elucidated. In this article, we propose a new hypothesis about the induction mechanism of febrile convulsions that takes into account the hypozincemia during fever. This hypozincemia activates the NMDA receptor, one of the glutamate family of receptors, which may play an important role in the induction of epileptic discharge.

Child↗

Development of artificial placenta: oxygen metabolism of isolated goat fetuses with umbilical arteriovenous extracorporeal membrane oxygenation.

To assess the oxygen utilization of extrauterine goat fetuses with arteriovenous extracorporeal membrane oxygenation via umbilical vessels, oxygen delivery (OD) and oxygen consumption (OC) were investigated in 19 long-term incubations (incubation periods 58-236 h). The OCs did not change (6.4 +/- 1.3 ml/min/kg, mean +/- SD, n = 227) when the ODs were more than 10 ml/min/kg, but were significantly suppressed when the ODs were less than 10 ml/min/kg. It was suggested that the oxygen metabolism of extrauterine goat fetuses is equivalent to that of fetuses in utero.

Animals↗

Early schizonts of Leucocytozoon caulleryi.

Sporozoites of Leucocytozoon caulleryi were inoculated intravenously into 26-day-old specific pathogen-free chickens. Six days after inoculation, early schizonts were detected in lung, spleen, and thymus. They existed separately and were spherical or ovoid, 30-35 microns in diameter, and had well defined walls.

Animals↗