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Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 181 records · Page 10Linked to original sources
PubMed2000

Dehydroepiandrosterone suppresses elevated hepatic glucose-6-phosphatase mRNA level in C57BL/KsJ-db/db mice: comparison with troglitazone.

Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia of diabetic C57BL/KsJ-db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA as well as troglitazone suppresses the elevated hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase) activities in C57BL/KsJ-db/db mice. In the present study, we evaluated the changes in mRNA of G6Pase and FBPase in db/db mice. Despite hyperinsulinemia, the G6Pase mRNA level of db/db mice was elevated as compared to their heterozygote littermate db/+m mice. In contrast, the FBPase mRNA level was not elevated in db/db mice. Administration of DHEA for two weeks significantly decreased the blood glucose level and the elevated G6Pase mRNA level in db/db mice. No significant changes were seen in the FBPase mRNA level after the administration of DHEA. Administration of troglitazone also decreased the blood glucose and G6Pase mRNA level in db/db mice although no changes were seen in the FBPase mRNA level. These results suggest that the elevation of G6Pase mRNA is important in elucidating the cause of insulin resistance, and that the G6Pase gene is at least one target for the hypoglycemic effects of DHEA as an insulin sensitizing agent in db/db mice.

Animals↗
PubMed2000

Depressive mood and suicide among middle-aged workers: findings from a prospective cohort study in Nagoya, Japan.

BACKGROUND: In Japan, mortality from suicide has peaked around 50 years old among men, with increasing trend after 65 years old, and this peak became more apparent in recent years. Beside this, "psychological autopsy" has revealed depression as one of the most important risk factors for suicide. There is, however, no cohort study which examined the relationship between depressive mood measured by simple method and suicide in middle-aged general population. METHODS: In 1989, baseline information was collected by a self-administered questionnaire, and 18,450 workers were followed up to March 31, 1995. All deaths observed during active service were identified, and when retired, its date was recorded. Among 5,352 male workers aged between 40 to 54, 11 committed suicide during follow-up period of 5 years. Analysis were carried out by Cox's proportional hazard model, controlling for age. RESULTS: Those who slept 9 hours or more per night demonstrated 12.14-fold risk of suicide compared with those who slept less than 9 hours. Smokers were more likely to commit suicide than non-smokers. Those who answered affirmatively to more than 7 out of 12 questions, which were derived from Zung self-rating depression scale, experienced an increased risk of suicide (RR 9.95; 95%CI: 1.89-52.44), even after adjusting for other confounding factors. CONCLUSION: We found an association between depressive mood and subsequent suicide in a middle-aged workers. Detailed observation and follow-up of those with depressive mood should be systematically organized with due attention and caution.

Adult↗
PubMed2000

Diagnostic value of a bedside test for cardiac troponin T in the patient with chest pain presenting to the emergency room.

Identification of patients with acute chest pain due to acute coronary syndrome is a common and difficult challenge for emergency physicians. A prospective study was conducted to assess the diagnostic value of a bedside test of cardiac troponin T in the emergency room setting. Forty-nine consecutive patients, who visited the emergency room within 6 hours of the onset of acute chest pain, were enrolled. Of the 26 patients who were ultimately diagnosed as having acute coronary syndrome, seven patients (27%) had positive cardiac troponin T assay results, whereas none of the patients without acute coronary syndrome had positive results (0%). For patients with acute coronary syndrome who presented later than 3 hours after the onset (n = 4), the test was positive in all cases (positive predictive value: 100%, negative predictive value: 100%, p < 0.01). However, the positive rate was only 14% for those who presented earlier than 3 hours after the onset (n = 22) (positive predictive value: 100%, negative predictive value: 47%, p = 0.84). In conclusion, bedside troponin T test results should be evaluated considering the time interval from the onset of chest symptoms.

Adult↗
PubMed2000

Effects of mitogen-activated protein kinase inhibitors on cerebral vasospasm in a double-hemorrhage model in dogs.

OBJECT: Mitogen-activated protein kinase (MAPK) may be involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. This study was conducted to investigate the ability of the MAPK inhibitors PD-98059 and U-0126 to reverse vasospasm in a double-hemorrhage model in dogs. METHODS: Twenty-two adult mongrel dogs of either sex, each weighing 18 to 24 kg, were divided randomly into four groups: control SAH (four dogs), vehicle- (dimethyl sulfoxide, six dogs), PD-98059- (six dogs), and U-0126-treated groups (six dogs). The double-hemorrhage model was created by an autologous blood injection into the cisterna magna on Days 0 and 2. An intracisternal injection of MAPK inhibitors was administered once per day on Days 3 through 6. Cerebral angiography was performed on Days 0 and 7 before the animals were killed. Western blot analysis was used to study the effects of hemorrhage and drug treatment on the MAPK immunoprecipitation. Severe vasospasm developed in the dogs in the control and vehicle-treated groups (basilar artery [BA] diameter reduction 46.6 +/- 5.5% and 49.3 +/- 4.6%, respectively). In the PD-98059-treated group, most of the dogs developed mild vasospasm (18.9 +/- 6.2%). In the U-0126-treated group, severe vasospasm was observed despite treatment (39.6 +/- 6.4%). The PD-98059 but not the U-0126 abolished MAPK immunoprecipitation in the spastic BAs. However, treatment with either PD-98059 or U-0126 improved the clinical scores of the dogs. CONCLUSIONS: The present study is the first in which the effects of MAPK inhibitors on vasospasm have been investigated in vivo. The authors demonstrate that MAPK may play a role in vasospasm and that PD-98059 is a potential candidate for the treatment of cerebral vasospasm.

Animals↗
PubMed2000

Absence of p53-mediated G1 arrest with induction of MDM2 in sterigmatocystin-treated cells.

P53 plays a critical role in G1 checkpoint after DNA damage. MDM2 gene is a p53 target gene and its protein forms a feedback loop with p53 and inhibits p53-mediated G1 arrest. Sterigmatocystin (ST) is a mycotoxin and carcinogen. In this study we show that exposure of cells to ST for 12 or 24 h resulted in failure of G1 arrest at both time points. Accordingly, p53 protein was not increased and p21WAF1 expression was inhibited at 12 h, and both proteins were weakly induced at 24 h after treatment with ST. Meanwhile, MDM2 protein was induced in a p53-dependent fashion by ST at both 12 and 24 h. The induction of MDM2 was coincident with the cellular responses of p53 and p21WAF1, and might contribute to the failure of G1 arrest in ST-treated cells. In addition, ST-treated cells exhibited G2M arrest, regardless of p53 status. Our results indicate that the carcinogenic effects of ST seem to be mediated by failure of p53-mediated G1 checkpoint.

Animals↗
PubMed2000

Unique characteristics of lacrimal glands as a part of mucosal immune network: high frequency of IgA-committed B-1 cells and NK1.1+ alphabeta T cells.

PURPOSE: Immunologic characterization of IgA-committed B-1 and B-2 cells, and unique subsets of T cells isolated from the murine lacrimal gland (LG), the primary exocrine tissue for the ocular surface, which is considered to be a part of the mucosal immune system. METHODS: Single cells were obtained from LGs of C57BL/6 mice by the enzyme dissociation method using collagenase type IV. Samples underwent flow cytometric analysis to characterize the unique subsets of T and B cells. To test the effectiveness of ocular vaccination, mice were immunized ocularly or nasally with cholera toxin (CT; 10 microg/mouse) suspended in phosphate-buffered saline. Antigen-specific immune responses were determined by isotype and CT-specific enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. RESULTS: When mononuclear cells (MC) isolated from LG samples were examined by flow cytometry, approximately 28% of cells were characterized as B220+ B cells. Because surface IgA+ (sIgA+) B cells develop from B-1 and B-2 lineages, it was important to examine which subset of B cells gives rise to LG sIgA+ B cells. Examination of the MC isolated from LG samples showed that approximately 4% of cells were sIgA+ B cells. Furthermore, nearly all these sIgA+ B cells (97.5%) belonged to the B-1 lineage, especially the B-1a cell line (B220low, CD5+). Of the isolated CD3+ T cells, 75% were alpha(beta) and 25% were gamma(delta)T-cell receptor positive. The proportion of NK1.1+ alpha(beta) T cells was higher (3%) in LG samples than in submandibular gland samples (0.5%). Ocular immunization with CT-induced antigen-specific mucosal (e.g., found in tear-wash and saliva samples) and systemic (e.g., serum) immune responses. The magnitude of antigen-specific antibody responses was comparable to those induced by nasal immunization. CONCLUSIONS: These results show that LG contains unique subsets of B (e.g., sIgA+ B-1 cells) and T (e.g., NK1.1+ alpha(beta)T cells) cells. Furthermore, as a part of the mucosal immune barrier, the LG is an important immunologic tissue for the ocular surface.

Animals↗
PubMed2000

[Essential thrombocythemia in transformation from myelodysplastic syndrome to acute myeloid leukemia with inv(3) after treatment for gastric cancer].

In March 1990, a 61-year-old man was given a diagnosis of essential thrombocythemia with a normal karyotype and subsequently treated with hydroxyurea. In November 1995, he underwent surgery for gastric cancer with thereafter received tegafur/uracil for 2 years. Refractory anemia with excess of blasts in transformation and chromosomal abnormalities including -5, -7, 20q-developed in August 1998. Combined chemotherapy with daunorubicin, cytarabine, mercaptopurine, and prednisolone, had only limited effectiveness. Acute myeloid leukemia was finally diagnosed in October 1998, and chromosomal analysis disclosed inv(3) in addition to -5 and -7. The appearance of inv(3) might be related to leukemic transformation of hematopoietic stem cell disease with an increase in the number of megakaryocytes and platelets.

Aged↗
PubMed2000

[Antiviral effect of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine on adenovirus].

PURPOSE: Adenovirus is the most frequent causative virus of conjunctivitis in Japan. Recently (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC) has been promoted as a new drug against adenoviral conjunctivitis. So we examined the antiviral activity of HPMPC against adenoviruses in vitro. METHOD: The antiviral activity of HPMPC against adenovirus (Ad) type 3, type 4, type 19, and type 37 isolated from conjunctivial scrapings in Japan and the prototype of adenovirus type 5 was examined by plaque reduction assay using A 549 cells in vitro. RESULTS: The 50% inhibitory dose (ID50) of HP-MPC was 3.50 (1.44-4.79) micrograms/ml for Ad type 3, 4.50 (4.17-4.92) micrograms/ml for Ad type 4, 2.11 (1.03-3.13) micrograms/ml for Ad type 5, 1.64 (1.40-2.02) micrograms/ml for Ad type 19, and 2.02 (1.17-2.73) micrograms/ml for type 37. The 50% cytotoxic dose of HPMPC for A 549 cells was 205 micrograms/ml by the deoxythimidine uptake inhibition test, and 537 micrograms/ml by the trypan blue exclusion inhibition test. CONCLUSIONS: HPMPC proved to be highly effective in inhibiting replication of adenoviruses at lower concentrations than the cytotoxic level in vitro.

Adenoviridae↗
PubMed2000

Genetic characterization of adenovirus strains isolated from patients with acute conjunctivitis in the city of São Paulo, Brazil.

Genome analysis was carried out on adenovirus strains isolated from patients with acute follicular conjunctivitis in the city of São Paulo, Brazil. Eighteen conjunctival scrapings, collected between December 1993 and March 1994, were analyzed by two methods: a combination of polymerase chain reaction with restriction fragment length polymorphism and viral DNA restriction analysis, carried out using 10 restriction endonucleases: BamHI, BglI, BglII, HindIII, KpnI, SacI, SalI, SmaI, XbaI, and XhoI. Among 11 adenovirus detected by cell culture isolation, nine were Ad8, and two were Ad7. By restriction analysis the Ad8 isolates were typed as two new variants-Ad8/D11 (seven of nine samples) and Ad8/D12 (two of nine samples). Ad7 isolates were identified as a subtype of the widespread genome type Ad7b and the virulent type Ad7h, a predominant genome type circulating in Argentina, Chile, and Uruguay but absent in Brazil until 1991.

Acute Disease↗
PubMed2000

Cerebral blood flow on xenon CT: correlation with the blood flow detected at the common carotid artery on ultrasonography.

To correlate cerebral blood flow (CBF) on xenon CT with the flow at common carotid artery (CCA) detected by color doppler ultrasonography, 82 patients (29 men, 53 women; 20-90 yrs) were examined. They included normal volunteers (n = 33), patients with cerebral infarction (n = 8), multiple lacunar infarcts (n = 12), dementia (n = 14), and parkinson disease (n = 15). Flow at the CCA was graded as extremely low (< 0.3 l/min), low (0.3-0.4), and normal (> 0.4). CBF was measured in the following distribution: anterior, middle, posterior cerebral arteries (ACA, MCA, PCA); white matter border zones (BZ); basal ganglia (BA), thalamus in two slices. CBF may be reduced in the BZ, cortical and deep gray matter with extremely low flow at CCA. We suggest that color doppler ultrasonography may aid in triage of patients for further CBF evaluation. As some overlap in CBF exists between normal and diseased groups with respect to low flow at CCA, color doppler ultrasonography must be evaluated in combination with xenon CT to reflect cerebral blood flow.

Adult↗
PubMed2000

[Efficacy and safety of cefozopran (CZOP) monotherapy and combination therapy with CZOP and amikacin (AMK) for infections accompanying hematological diseases].

We evaluated efficacy and safety of monotherapy with CZOP (1-2 g x 2/day) and combination therapy with CZOP (1-2 g x 2/day) and AMK (200 mg x 2/day) for infections in patients with hematological diseases. Efficacy was evaluated in 71 patients of monotherapy group and 70 patients of combination therapy group. Underlying diseases were mostly leukemia and lymphoma. Infections included sepsis, suspected sepsis, pneumonia and so on. Efficacy in CZOP monotherapy was excellent in 21 patients (31.3%), good in 23 patients (34.3%), fair in 5 patients (7.5%) and the efficacy rate was 65.7%. On the other hand, in combination therapy, each was 14 patients (21.2%), 23 patients (34.8%), 12 patients (18.2%) and the efficacy rate was 56.1%. Side effects such as eruption were noted in 2 patients. Abnormal laboratory findings were noted in 9 patients. All side effects as well as abnormal laboratory findings were minimal. It was concluded that CZOP monotherapy was effective in the treatment of various infections accompanying hematological diseases.

Adolescent↗
PubMed2000

[Antiphospholipid antibody syndrome in adverse pregnancy].

As a single test beta 2-glycoprotein I-dependent anticardiolipin antibody(beta 2GPI-dependent aCL) appears to be superior to cofactor-independent anticardiolipin antibody or any other single conventional antiphospholipid antibody for the detection of autoantibody-associated conditions of reproductive failure. beta 2GPI-dependent aCL are significantly highly associated with adverse pregnancy outcomes in healthy pregnant women and can be used for prediction, whereas beta 2GPI-independent aCL can not. Anticardiolipin antibodies and Lupus anticoagulant(LAC) define two distinct but partly related populations. LAC and anti beta 2GPI antibodies appear to be associated with pregnancy loss, with LAC being linked not only to spontaneous abortions in the first trimester but also to miscarriages in the second trimester. The live birth rate in patients strongly positive for antiphospholipid antibody(aPL) is lower than that in patients with moderate aPL production even if treatment with prednisolone, heparin, high-dose immunoglobulin, and/or low-dose aspirin is performed during pregnancy. However, low-dose aspirin is useful to treat cases of moderate aPL so that distinction between the two groups is warranted.

Abortion, Habitual↗
PubMed2000

[Bacterial infection in the conjunctiva of patients with adenoviral conjunctivitis].

PURPOSE: We evaluate the microbiological features of mixed infection in adenovirus-infected conjunctiva. SUBJECTS: Isolation of bacteria was performed in 82 samples of adenoviral conjunctivitis at six eye clinics in Japan. METHODS: For microbiological diagnosis, we performed immunochromatography (IC) and polymerase chain reaction--restriction fragment length polymorphism (PCR-RFLP) analysis for detection and serotyping of adenovirus, and PCR for detection of herpes simplex virus (HSV) and Chlamydia trachomatis antigens out of 82 samples with adenoviral conjunctivitis. RESULTS: Pathogenic bacteria were isolated in 6 samples out of 82. Out of these 6 cases, 5 samples were gram-negative rods and most of them were Flavobacterium meningosepticum (4 samples). Adenovirus type 8 was isolated from all these mixed infection cases. However, HSV-1 and Chlamydia trachomatis were not found. CONCLUSIONS: From these results, it is suggested that gram-negative rods, especially F. meningosepticum, are the most common bacteria causing mixed bacterial infection in adenoviral conjunctivitis.

Adenovirus Infections, Human↗
PubMed2000

SM22alpha promoter targets gene expression to vascular smooth muscle cells in vitro and in vivo.

BACKGROUND: Gene transfer into vascular smooth muscle cells (vsmcs) holds promise for studying the pathogenesis of arterial disorders. However, a potential limitation of vectors with heterologous promoters is organ toxicity resulting from unrestricted transgene expression. Vascular smooth muscle cell-specific gene expression could increase the safety of vectors for vascular diseases. MATERIALS AND METHODS: To develop vectors that target gene expression to vsmcs, we constructed vectors encoding human placental alkaline phosphatase (hpAP) and chloramphenicol transferase (CAT) driven by a 441-bp region of the murine SM22alpha promoter (AdSM22alpha-hpAP). RESULTS: Transfection of AdSM22alpha-hpAP into vascular and nonvascular cells resulted in the expression of alkaline phosphatase (AP) in primary arterial and venous smcs, but not in primary endothelial cells or National Institutes of Health (NIH) 3T3 cells. Expression of AP was observed on 32.5 +/- 1.4% of primary pig vsmcs-infected AdSM22alpha-hpAP at a multiplicity of infection (MOI) of 500; whereas, infection with AdCMV-hpAP resulted in 100 +/- 0.0% expression at a MOI of 250. In vitro, expression from the heterologous cytomegalovirus (CMV) promoter was approximately 10(3)-fold higher in vsmcs, compared with the SM22alpha promoter. Following introduction of AdSM22alpha-hpAP vectors into balloon-injured pig arteries, AP recombinant protein was detected in neointimal (2.23 +/- 1.14%) and medial (0.56 +/- 0.21%) smcs, but not in endothelial or adventitial cells. In contrast, AdCMV-hpAP vectors led to AP expression in intimal endothelial and smcs cells (39.14 +/- 10.09%) and medial smcs (2.84 +/- 1.05%). AP expression was not observed in endothelial or vsmcs following transfection with the control vector, adenoviral vector lacking E1 (AddeltaE1). CONCLUSIONS: The SM22alpha promoter programs recombinant gene expression exclusively to vascular smcs in vitro and in vivo. Although expression levels are lower than with heterologous promoters, these vectors may provide a safe and effective tool for gene therapy of vascular diseases.

Animals↗
PubMed2000

Calcium phosphate crystal-associated proteins: alpha2-HS-glycoprotein, prothrombin F1, and osteopontin.

PURPOSE: To elucidate the process of urinary stone formation, many urinary constituents have been examined as inhibitors or promoters. MATERIALS AND METHODS: We analyzed specific binding proteins of calcium phosphate (CaP) crystals generated in human urine and found that the separated proteins were alpha2-HS-glycoprotein, prothrombin fragment 1 (PTF1), and osteopontin (OPN). We also studied their inhibitory effects on calcium oxalate crystallization and the quantitative differences in urinary excretion of the proteins in healthy individuals and stone formers. RESULTS: Both PTF1 and OPN had strong inhibitory effects on growth of calcium oxalate crystals. No differences in alpha2-HS-glycoprotein were found between healthy subjects and stone formers. Urinary concentrations of PTF1 and OPN were lower in stone formers than in healthy controls. No differences in these proteins were seen between single and recurrent stone formers. CONCLUSION: Low urinary concentrations of PTF1 and OPN might be one reason for stone formation.

Adolescent↗
PubMed2000

[Midbrain infarction presenting isolated inferior rectus nuclear palsy].

We presented a patient of isolated inferior rectus muscle palsy from midbrain lacunar infarction involving the oculomotor nucleus. The patient noticed sudden onset diplopia gazing to the right side, especially to the right-lower direction. He did not have any other symptom, and neurological examination revealed no other findings. Brain MRI documented the focal hyperintense lesion on T2-weighted images in the right-median midbrain ventral to the aqueduct at the level of the superior colliculus. This lesion involved the right oculomotor nucleus, especially the dorso-lateral subnucleus extend to the inferior rectus muscle. The oculomotor nuclear complex consists of one unpaired subnucleus and four paired subnuclei. Among them, the inferior rectus subnucleus lies dorso-laterally. So nucleus lesion may cause isolated weakness of one of muscles innervated by the oculomotor nerve. Among them the isolated inferior rectus muscle palsy can occur relatively.

Aged↗
PubMed2000

The effect of high salt intake on the mandibular bone loss in Dahl-Iwai salt-sensitive rat.

The purpose of this study was to evaluate the effect of high salt intake on the mandibular bone in Dahl-Iwai salt-sensitive (DS) rats. Twenty-eight 11-week-old male DS rats were divided into four groups (n=7). The control groups received a normal (0.2% NaCl) diet while the experimental groups received a diet supplemented with 8.0% NaCl. The systolic blood pressure was significantly increased in the experimental groups compared to the control groups. The animals were sacrificed under ether anesthesia at the 8th week or the 22nd week of the experiment. The biochemical data in plasma and urine suggested negative calcium balance in the experimental groups compared to the control groups. The bone mineral density was significantly reduced at the 22nd week of high salt loading. The histomorphometric analysis suggested that the reduction of the mandibular bone volume had already started by the 8th week of high salt loading along with the increased bone resorption and the decreased bone formation, and that the improper bone remodeling balance became normalized by the 22nd week of high salt loading. In conclusion, these results indicate that a high salt intake causes not only severe hypertension but also a mandibular bone reduction in the DS rats.

Absorptiometry, Photon↗