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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 487 records · Page 27Linked to original sources

Glucokinase gene in gestational diabetes mellitus: population association study and molecular scanning.

Mutations of the glucokinase gene result in early-onset familial Type 2 (non-insulin-dependent) diabetes mellitus, and several members of the mutant glucokinase kindreds were originally diagnosed as having gestational diabetes. This study examined the glucokinase gene in 270 American Black women, including 94 with gestational diabetes whose diabetes resolved after pregnancy (gestational diabetes only), 77 with gestational diabetes who developed Type 2 diabetes after pregnancy (overt diabetes), and 99 normal control subjects who were recruited during the peripartum period. Two simple sequence repeat polymorphisms flanking either end of the glucokinase gene were evaluated. No association was found between glucokinase alleles and gestational diabetes only or overt diabetes, after adjustment for multiple comparisons. To detect single base changes, all 11 exons and proximal islet and liver promoter regions were examined by polymerase chain reaction plus single-stranded conformational polymorphism analysis in 45 gestational diabetes only patients who had not yet developed Type 2 diabetes. Nine coding region variants were identified: Ala11 (GCC) to Thr11 (ACC) in islet exon 1, and 8 variants either in untranslated regions or in the third base of a codon. Four variant sites were found in introns, but none in splicing consensus sequences. Analysis of the promoter regions revealed two common variants, G-->A at islet -30 (24%), and G-->A at liver -258 (42%). The frequencies of the promoter variants, determined by allele specific polymerase chain reaction analysis, but did not differ among the three groups. Thus, no significant coding sequence glucokinase mutations were found in 90 alleles from 45 patients with gestational diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of aprotinin on acute recovery of cerebral metabolism in piglets after hypothermic circulatory arrest.

Brain protection during cardiopulmonary bypass and hypothermic circulatory arrest is incomplete. Activation of blood protease cascades may contribute to cellular injury under these conditions. To test this hypothesis, effects of the protease inhibitor aprotinin on recovery of brain energy metabolism after hypothermic circulatory arrest were studied in the piglet. Twenty-four 4-week-old piglets (10 aprotinin-treated and 14 control) underwent core cooling, 1 hour of circulatory arrest at 15 degrees C, reperfusion and rewarming (45 minutes), and normothermic perfusion (3 hours) on cardiopulmonary bypass. Cerebral high-energy phosphate concentration and intracellular pH were studied by phosphorus-31 magnetic resonance spectroscopy in 12 animals. In the remaining animals cerebral and regional blood flow were measured with radioactive microspheres and carotid artery blood flow was measured with an electromagnetic flowmeter. Cerebral oxygen and glucose extraction were measured, and vascular resistance responses to endothelium-dependent (acetylcholine) and -independent (nitroglycerin) vasodilators were calculated. Recovery of cerebral adenosine triphosphate (p = 0.02) and intracellular pH (p = 0.04) in the initial 30 minutes of reperfusion was accelerated in the aprotinin-treated piglets. These piglets showed a greater in vivo cerebral and systemic endothelium-mediated vasodilation (acetylcholine response: cerebral p < 0.01, systemic p = 0.04) after reperfusion. The response to endothelium-independent vasodilation (nitroglycerin) was the same in both groups. Carotid blood flow tended to be greater at 20 minutes of reperfusion and less during 45 to 80 minutes after reperfusion in the aprotinin-treated animals. Brain water content postoperatively was 0.8077 in the aprotinin group and 0.8122 in control animals (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Familial amyotrophic lateral sclerosis (ALS) in Japan associated with H46R mutation in Cu/Zn superoxide dismutase gene: a possible new subtype of familial ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disorder that results in relentless damage to the motor neuron system. Although about 5-10% of cases are familial, the pathophysiologic process of ALS remains unknown. We identified a novel point mutation A to G in exon 2 of the Cu/Zn SOD gene, resulting in an amino acid substitution of histidine46 by arginine (H46R), in two Japanese familial ALS (FALS) families. The segregations of the mutation were evident. The enzymatic activities of Cu/Zn SOD of peripheral red blood cell lysate were reduced to about 80% in the affected members, compared with other non-affected family members. The patients in these families are clinically characterized by relative late onset, initial involvement in lower extremities, relative rare impairment of bulbar muscles and much slow progression of muscular weakness and atrophy, compared with other Japanese FALS cases who have no mutation in the Cu/Zn SOD gene. These findings suggest that the H46R mutation in Cu/Zn SOD gene is highly related to this unique subtype of FALS.

Adult↗

Ultrastructural cytochemical demonstration of proteoglycans and calcium in the extracellular matrix of chondroblastomas.

To clarify the characteristics of the extracellular matrix of chondroblastomas, six cases were studied under the electron microscope, with special reference to proteoglycans and calcium in the cellular areas. In ruthenium hexammine trichloride (RHT)-stained sections the matrix was observed to be composed of rounded or polygonal fine granules and unbanded thin filaments that appeared to link neighboring granules together. Treatment with potassium-pyroantimonate showed intracellular accumulation of precipitates, mainly localized within the cisternae of the rough endoplasmic reticulum as well as in the extracellular matrix. The presence of calcium in the precipitates was confirmed using x-ray energy dispersive analysis. These findings, similar to characteristic features observed in calcifying systems, support the theory that chondroblastomas are of chondrogenic origin.

Calcium↗

Tendon repair using flexor tendon splints: an experimental study.

Mechanical strength of tendon repair using Dacron tendon splints across the laceration site were evaluated in human cadaver profundus tendons; the splints were placed both on the dorsal surface and internally within the tendon substance. Comparison was made to modified Kessler, Becker, and Savage repair techniques. Ultimate tensile strength was 2.55 kgf for the Kessler, 3.00 kgf for the Becker, 8.29 kgf for the Savage, 8.46 kgf for the internal tendon splint, and 8.10 kgf for the dorsal tendon splint; the Savage and both Tendon Splints techniques had significant higher tensile strength than the Kessler and Becker. Gap strength was 1.44 kgf for the Kessler, 2.22 kgf for the Becker, 2.45 kgf for the Savage, 2.05 kgf for internal tendon splint, and 3.15 kgf for the dorsal tendon splint. The dorsal tendon splint technique showed significant greater gap strength than the other four techniques. There was no significant difference in the magnitude of the gap during cyclic testing of these techniques; however, three of seven Kessler repairs failed and one of six Becker repairs failed. The results of these cadaver studies suggest that both tendon splint repair techniques are comparable to the Savage and may have sufficient strength to allow postoperative active motion against minimal resistance. Further in vivo testing is in order.

Cadaver↗

Dorsal and circumferential sheath reconstructions for flexor sheath defect with concomitant bony injury.

Dorsal and circumferential flexor sheaths were reconstructed by autogenous sheath graft in flexor tendon repair in 28 white leghorn chickens. The effect of the sheath reconstructions was evaluated by use of an experimental model of tendon transection associated with bony injury, superficial tendon excision, and 3 weeks of immobilization. Six weeks after reconstruction, the gliding excursion was assessed and adhesion formation, tendon healing, and survival of the grafted sheath were evaluated both macroscopically and histologically. Dorsal and circumferential sheath grafts resulted in tendon gliding that was significantly better than the group with sheath defect not reconstructed. The adhesion formation was apparently less severe, and tendon healing was better in the groups with sheath reconstruction than in the group without reconstruction. The group with dorsal sheath reconstruction did not differ significantly from that with circumferential reconstruction in gliding excursion and adhesion formation. This study demonstrates that separation of the injured tendons from the bony surface by autogenous sheath grafts may be beneficial to tendon gliding and for reducing adhesion formation.

Animals↗

Purification and characterization of 3 alpha/beta-hydroxysteroid dehydrogenase from mature porcine testicular cytosol.

NADPH-dependent 3 alpha/beta-hydroxysteroid dehydrogenase (3 alpha/beta-HSD) was purified to apparent homogeneity from testicular cytosol of mature pigs. The purified enzyme catalyzes the conversion of 5 alpha-dihydrotestosterone (5 alpha-DHT) to both 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol. The molecular weight of the enzyme was estimated to be 31 kDa by SDS-polyacrylamide gel electrophoresis and 40 kDa by gel filtration chromatography indicating that the native 3 alpha/beta-HSD is a monomer. The isoelectric point of the purified enzyme was found to be 6.2 by density gradient isoelectric focusing and 6.4 by chromatofocusing. The enzyme reduced both 5 alpha- and 5 beta-DHT, 5 alpha- and 5 beta-dihydroprogesterone, 5 alpha- and 5 beta-dihydrocortisol, prostaglandin E2, 13,14-dihydro-15-keto-prostaglandin E2 and 13,14-dihydro-15-keto-prostaglandin F2 alpha. Moreover, the enzyme caused rapid reduction of other carbonyl compounds including aldehydes, ketones and quinones. The rates of reduction of these compounds are fast relative to the rates of reduction of steroids and prostaglandins. The purified enzyme was inhibited by AgNO3, SH-reagent, quercetin, hexesterol, stilbestrol, disulfiram and divalent cation such as Cu2+, Hg2+ and Cd2+. The two enzymes show certain similarities (e.g. molecular weight, cross-reactivity to a common antibody) and certain striking differences (e.g. pI, effects of various inhibitors and greater enzyme activity towards steroids (neonatal form) or prostaglandins (mature form). Reasons are give for suggesting that these enzymes are closely related to carbonyl reductase.

3-Hydroxysteroid Dehydrogenases↗

Omentoplasty for postpneumonectomy bronchopleural fistulas.

Postpneumonectomy fistula is one of the most serious complications in general thoracic surgery and remains difficult to manage. From 1984 to 1991, we successfully used pedicled omentum for the treatment of postpneumonectomy bronchopleural fistulas (omentoplasty) in five patients, four of whom had thoracic empyema. For bronchopleural fistulas without early postoperative infection, single-stage closure was performed which was then covered with pedicled omentum. Omentoplasty was performed successfully in patients with thoracic empyema, after open or closed drainage. Open thoracotomy was useful when closed drainage was ineffective. Even after open thoracotomy, closure of the wound was achieved. All five patients could be discharged. Omentoplasty was useful in the therapy of postpneumonectomy bronchopleural fistula even in the presence of thoracic empyema.

Aged↗

Effects of MK-801 and NBQX on acute recovery of piglet cerebral metabolism after hypothermic circulatory arrest.

Brain protection during open heart surgery in the neonate and infant remains inadequate. Effects of the excitatory neurotransmitter antagonists MK-801 and NBQX on recovery of brain cellular energy state and metabolic rates were evaluated in 34 4-week-old piglets (10 MK-801, 10 NBQX, 14 controls) undergoing cardiopulmonary bypass and hypothermic circulatory arrest at 15 degrees C nasopharyngeal temperature for 1 h, as is used clinically for repair of congenital heart defects. MK-801 (dizocilpine) (0.75 mg/kg) or NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline] (25 mg/kg) was given intravenously before cardiopulmonary bypass. Equivalent doses were placed in the cardiopulmonary bypass prime plus continuous infusions after reperfusion (0.15 mg kg-1h-1 and 5 mg kg-1h-1). Changes in high-energy phosphate concentrations and pH were analyzed by magnetic resonance spectroscopy in 17 animals until 225 min after reperfusion. Cerebral blood flow determined by radioactive microspheres as well as cerebral oxygen and glucose consumption were studied in 17 other animals. Cerebral blood flow and oxygen consumption were depressed relative to control by both MK-801 and NBQX at baseline. Recovery of phosphocreatine (p = 0.010), ATP (p = 0.030), and intracellular pH (p = 0.004) was accelerated by MK-801 and retarded by NBQX over the 45 min of rewarming reperfusion and the first hour of normothermic reperfusion. The final recovery of ATP at 3 h and 45 min reperfusion was significantly reduced by NBQX (46 +/- 26% baseline, mean +/- SD) versus control (81 +/- 19%) and MK-801 (75 +/- 8%) (p = 0.030). Cerebral oxygen consumption recovered to 105 +/- 30% baseline in group MK-801 and 94 +/- 31% in control but only to 61 +/- 22% in group NBQX (p = 0.070). Cerebral blood flow stayed significantly lower in group NBQX relative to control. Thus, MK-801 accelerates recovery of cerebral high-energy phosphates and metabolic rate after cardiopulmonary bypass and hypothermic circulatory arrest in the immature animal. At the dosage used NBQX exerts an adverse effect.

Animals↗

Reaction times to neon, LED, and fast incandescent brake lamps.

Standard incandescent brake lamps have a relatively slow rise time. It takes approximately a quarter of a second for them to reach 90% of asymptotic light output, causing potential delays in responses by following drivers. The present study evaluated reaction times to brake signals from standard incandescent brake lamps and from three alternative brake lamps with substantially faster rise times: neon, LED, and fast incandescent. The study, performed in a laboratory, simulated a daytime driving condition. The subject's task was to respond as quickly as possible to the onset of either of two brake lamps in the visual periphery, while engaged in a central tracking task. Brake signals were presented at two levels of luminous intensity. The results showed that reaction times to the alternative brake lamps were faster than to the standard incandescent lamp, with the advantage averaging 166 ms for the LED and neon lamps, and 135 ms for the fast incandescent lamp. A reduction of the signals' luminous intensity from 42 cd to 5 cd increased the reaction time by 84 ms.

Adult↗

Preproenkephalin gene expression in the rat cerebral cortex during chronic tracheal stenosis.

To evaluate whether the endogenous opioid system is activated in the higher brain centre while a chronic resistance to airflow, we examined changes of mRNAs for preproenkephalin (PPE)-A, which is a precursor of enkephalin, and for 70 kD heat shock protein (HSP70) in the cerebral cortex of rat brain during chronic tracheal stenosis. Northern blot revealed that PPE-A mRNA was induced at 3 days of airway stenosis. In situ hybridization revealed that PPE-A mRNA was gradually induced in frontal cortex. The significant induction of PPE-A mRNA was observed at 3 and 7 days. However, no significant induction of HSP70 gene was observed. These results suggest that the endogenous opioid system may be at work as an important compensatory mechanism to reduce the respiratory sensation during chronic respiratory stress.

Animals↗

Effect of newer quinolones on the extra- and intra-cellular chemiluminescence response of human polymorphonuclear leucocytes.

The direct effect of four quinolones on the intracellular production and extracellular release of reactive oxygen species was investigated in vitro using a chemiluminescence (CL) assay. Polymorphonuclear leucocytes (PMNs) were obtained from healthy volunteers and exposed for 10 min at 37 degrees C to 1.6, 6.25 and 25 mg/L ofloxacin, ciprofloxacin, sparfloxacin and temafloxacin. The luminol-dependent CL response of the PMNs was then measured for 30 min following stimulation with nonopsonized zymosan or phorbol myristate acetate (PMA). The intracellular CL response was also measured for 30 min during phagocytosis of lumispheres. The integrated CL was calculated and compared for cells which were incubated with the antibiotic and unincubated controls. Preincubation with ofloxacin resulted in increased zymosan and PMA-induced, luminol-dependent CL. Similar increases were observed for ciprofloxacin except that 25 mg/L decreased the PMA-induced, luminol dependent CL. Preexposure to ofloxacin and ciprofloxacin did not affect lumisphere-induced CL significantly, although there was a tendency for this to decrease after exposure to ciprofloxacin. In contrast sparfloxacin and temafloxacin caused progressive decreases in zymosan and PMA-induced, luminol-dependent PMN CL which reached statistical significance at the higher concentrations. The same pattern was observed in the experiments using lumispheres. These findings indicate that these quinolones modulate the oxygen metabolism of PMNs and that this effect varies with the individual drug.

Anti-Infective Agents↗

An outbreak of group B streptococcus infection in a neonatal nursery and subsequent trial for prophylaxis of nosocomial transmission.

An outbreak of sepsis and meningitis caused by group B streptococcus occurred in three very low birthweight infants. To prevent further nosocomial transmission, immune globulin and ampicillin sodium were administered intravenously to other very low birthweight infants. After this prophylaxis, no other infants were involved in this outbreak. Immuno- and chemoprophylaxis may be considered as procedures to prevent nosocomial infection for very low birthweight infants.

Ampicillin↗

[Study of neutrophil dysfunctions in the elderly using a chemiluminescence method].

To evaluate the cause of the vulnerability to infections in the elderly, the ability of neutrophil to generate reactive oxygen species was assessed by a luminol-dependent chemiluminescence (CL) assay after stimulation with non-opsonized zymosan, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans and lumispheres in elderly patients aged 70 to 93 years. The integrated CL for 20 minutes of whole blood and neutrophils induced by zymosan in the elderly was significantly lower than that in healthy young adults, and the integrated CL of neutrophils induced by lumispheres was also significantly lower in the elderly aged 80 years and over. When bacterial infection occurred in the elderly, the levels of CL were elevated and decreased in the convalescence. This response is proper for host-defense mechanism against infection. However, whole blood CL response was not fully activated in any patients of the elderly during bacterial infection. In these cases lower white blood cell counts, lower neutrophil counts, or the decreased level of the serum total protein, albumin, total cholesterol or cholinesterase were observed. Relationship between malnutrition and the ability of neutrophil to generate reactive oxygen species was suggested. Furthermore, I evaluated the priming effect of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) on whole blood CL. The CL responses stimulated with non-opsonized zymosan or P. aeruginosa were enhanced by pretreatment with TNF-alpha and LPS in healthy young adults. On the other hand, no significant priming effect was observed when blood from elderly patients were incubated with each primer. These findings suggest that the impairment in the generation of reactive oxygen species of the neutrophils and the decrease in reactivity to LPS and TNF-alpha that activate neutrophils at the site of infection and potentiate host defense against invading bacteria, may contribute to susceptibility to infection in the elderly.

Aged↗

[A case of mefloquine-resistant Plasmodium falciparum malaria with convulsion after antimalarial treatment].

We report a case of 40-year-old with chloroquine- and mefloquine-resistant Plasmodium falciparum. He had a single grand mal seizure 37 days following retreatment with quinine intravenously, which resulted in rapid clearance of fever and parasitemia, in addition to mefloquine. He had a long history of seizures, which were well controlled by phenytoin. Because he has never had such a seizure before and computerized tomographic scanning of the brain after admission showed no abnormal findings which caused convulsions, it seemed to be an adverse reaction caused by antimalarial drugs. It is possible that a double or triple combination treatment for the emergence of multiresistant falciparum malaria might more frequently produce severe side effects, such as psychiatric reactions and convulsions. This case suggests that physicians must have a long follow-up period for chronic toxicity of antimalarial drugs, especially after using drug combinations for falciparum malaria.

Adult↗

[Two cases of Campylobacter fetus subsp. fetus sepsis].

We encountered two relatively rare cases of sepsis due to Campylobacter fetus subsp. fetus (C. fetus). Case 1. A 54-year-old female with abdominal polysurgery developed a slight fever and vomiting in August 1984. Despite the administration of some digestive drugs by her family doctor, these symptoms continued. In mid-October, she was hospitalized with high fever with chill and rigor on the skin. On the third hospital day, C. fetus was detected in the blood culture. After combination chemotherapy of intravenous drip infusion of latamoxef (LMOX) (2 g/day) and oral administration of erythromycin (EM) (800 mg/day), her symptoms improved. Case 2. A 57-year-old male with diabetic retinopathy and nephropathy was hospitalized because of slight fever, general edema and pleural effusion. On the 6th hospital day, C. fetus was detected in the blood culture and he was diagnosed with sepsis. Under treatment with the intravenous drip of LMOX (2 g/day) and oral administration of EM (1200 mg/day), his condition improved. Both cases had common underlying diseases such as hypoproteinemia with edema and problems in the lower intestinal tract; the former had polysurgery and malabsorption syndrome, the latter had diffuse ulceration of the colon. Such underlying conditions may have permitted the invasion of C. fetus into the blood.

Bacteremia↗