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Biomedical subjects

Y Imai

Publications and source records attributed to Y Imai.

At least 127 records · Page 7Linked to original sources
PubMed2001

Evidence for the physiological and pathological roles of adrenomedullin from genetic engineering in mice.

Adrenomedullin (AM) has been implicated as having hypotensive as well as protective effects on organs and vessels against different kinds of injuries. To elucidate the in vivo pathophysiological roles of adrenomedullin, we established transgenic mice (AMTg) overexpressing adrenomedullin driven by preproendothelin-1 promoter and adrenomedullin knockout mice (AMKO). Blood pressure in AMTg was significantly lower than that in wild-type mice, and AMTg was significantly resistant to lipopolysaccharide-induced septic shock and vascular injuries. On the other hand, heterozygotes of AMKO, AM(+/-), were fully viable and hypertensive as compared with wild littermates. Mice homozygous for adrenomedullin null mutation (AM-/-) were embryonic lethal, and no embryos could survive beyond the midterm of gestation. Collectively, our findings indicate the indispensable role of adrenomedullin in circulatory homeostasis and the organ protection as well as the fetal morphogenesis and the maintenance of pregnancy.

Adrenomedullin↗
PubMed2001

EP1 and EP4 receptors mediate exocytosis evoked by prostaglandin E(2) in guinea-pig antral mucous cells.

Effects of prostaglandin E(2) (PGE(2)) on exocytosis of mucin were studied in mucous cells isolated from guinea-pig antrum using video-microscopy. Stimulation with PGE(2) elicited a sustained increase in the frequency of exocytotic events in a dose-dependent manner, which was under regulation by both Ca(2+) and cAMP. Stimulation with a selective prostanoid EP4 receptor agonist (ONO-AEI-329, 10 microM), which activates cAMP signals, elicited a sustained increase in the frequency of exocytotic events (30 % of that evoked by 1 microM PGE(2)). Stimulation with an EP1 agonist (17-P-T-PGE(2), 1 microM), which activates Ca(2+) signals, increased the frequency of exocytotic events to a lesser extent (5 % of that evoked by 1 microM PGE(2)), while addition of an EP1 antagonist (ONO-8713, 10 microM) decreased the frequency of exocytotic events (approximately 40 % of that evoked by 1 microM PGE(2)). However, addition of the EP1 agonist potentiated the frequency of exocytotic events evoked by the EP4 agonist or forskolin (which elevates cAMP levels) and increased the sensitivity of the exocytotic events to forskolin. These results suggest that the Ca(2+) signal activated via the EP1 receptor potentiates the cAMP-regulated exocytotic events activated via the EP4 receptor during PGE(2) stimulation, by increasing the sensitivity of the exocytotic response to cAMP. In conclusion, exocytotic events in PGE(2)-stimulated antral mucous cells were regulated by interactions between EP1 and EP4 receptors. Experimental Physiology (2001) 86.4, 451-460.

Animals↗
PubMed2001

Determination of Helicobacter pylori virulence by simple gene analysis of the cag pathogenicity island.

Nucleic acid amplification was performed for five loci in the cag pathogenicity island (PAI) of Helicobacter pylori (comprising cagA, the cagA promoter region, cagE, cagT, and the left end of cagII [LEC]), and gastric inflammation in patients was evaluated. Of 204 H. pylori isolates from Japanese patients (53 with peptic ulcer, 55 with gastric cancer, and 96 with chronic gastritis), 197 (96.6%) were positive for all five loci. Two isolates (1%) were negative for all five loci, and five isolates (2.4%) were positive for only cagA and LEC. These latter seven isolates were all from patients with mild chronic gastritis. Neutrophil infiltration in gastric mucosa was significantly milder in patients infected with partially or totally deleted-PAI strains than in those with intact-PAI strains. The cagE gene was a more accurate marker of an intact cag PAI than the cagA gene, and cagE seemed to be more useful in discriminating between H. pylori strains causing different rates of disease progression.

Adult↗
PubMed2001

Autoregulation of the dnaA-dnaN operon and effects of DnaA protein levels on replication initiation in Bacillus subtilis.

In Escherichia coli, the DnaA protein level appears to play a pivotal role in determining the timing of replication initiation. To examine the effects on replication initiation in B. subtilis, we constructed a strain in which a copy of the dnaA gene was integrated at the purA locus on the chromosome under the control of an isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible promoter. However, increasing the DnaA level resulted in cell elongation and inhibition of cell growth by induction of the SOS response. Transcription of the native dnaA-dnaN operon was greatly reduced at high DnaA levels, but it was increased in a dnaA-null mutant, indicating autoregulation of the operon by DnaA. When a copy of the dnaN gene was added downstream of the additional dnaA gene at purA, the cells grew at high DnaA levels, suggesting that depletion of DnaN (beta subunit of DNA polymerase III) within the cell by repression of the native dnaA-dnaN operon at high DnaA levels was the cause of the SOS induction. Flow cytometry of the cells revealed that the cell mass at initiation of replication increased at a lower DnaA level and decreased at DnaA levels higher than those of the wild type. Proper timing of replication initiation was observed at DnaA levels nearly comparable to the wild-type level. These results suggest that if the DnaA level increases with progression of the replication cycle, it could act as a rate-limiting factor of replication initiation in B. subtilis.

Bacillus subtilis↗
PubMed2001

Identification of the hexon region of an adenovirus involved in a new outbreak of keratoconjunctivitis.

We tested 15 adenovirus (Ad)-positive patients involved in a case of nosocomial spread of keratoconjunctivitis. A neutralization test, PCR-restriction fragment length polymorphism analysis, and sequencing of the hypervariable regions of the hexons were performed in order to identify the type of Ad involved. The serotype of the Ad was not identical to any published Ad sequence by either method.

Adenovirus Infections, Human↗
PubMed2001

Comparison of lung protection strategies using conventional and high-frequency oscillatory ventilation.

This study compared pathophysiological and biochemical indexes of acute lung injury in a saline-lavaged rabbit model with different ventilatory strategies: a control group consisting of moderate tidal volume (V(T)) (10-12 ml/kg) and low positive end-expiratory pressure (PEEP) (4-5 cmH(2)O); and three protective groups: 1) low V(T) (5-6 ml/kg) high PEEP, 2-3 cmH(2)O greater than the lower inflection point; 2) low V(T) (5-6 ml/kg), high PEEP (8-10 cmH(2)O); and 3) high-frequency oscillatory ventilation (HFOV). The strategy using PEEP > inflection point resulted in hypotension and barotrauma. HFOV attenuated the decrease in pulmonary compliance, the lung inflammation assessed by polymorphonuclear leukocyte infiltration and tumor necrosis factor-alpha concentration in the alveolar space, and pathological changes of the small airways and alveoli. Conventional mechanical ventilation using lung protection strategies (low V(T) high PEEP) only attenuated the decrease in oxygenation and pulmonary compliance. Therefore, HFOV may be a preferable option as a lung protection strategy.

Animals↗
PubMed2001

Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis.

Radiation pneumonitis (RP) is the most common complication of radiotherapy for thoracic tumours. The aim of this study was to evaluate the significance of pulmonary surfactant proteins (SP)-A and SP-D as new serum markers for RP. Twenty-five patients with lung tumour, who had received radiotherapy, were studied. At the completion of radiotherapy, the presence of RP was judged by chest plain radiography and chest high resolution computed tomography (HRCT). RP findings detected on chest plain radiography were seen in only three of 12 patients in whom RP was detected by HRCT. Nevertheless, both SP-A and SP-D concentrations in sera from the patients with RP were significantly higher than those from the 13 patients without RP (p = 0.0065, p = 0.0011, respectively). As with SP-A, ratios of SP-D at the completion, compared to at the initiation (1 week post/pre ratio), were also significantly higher in patients with RP than in patients without RP. When a post/pre ratio > 1.6 was considered positive, the SP-A and SP-D assays showed an 83% and 85% specificity, respectively. In conclusion, serum assays of surfactant proteins A and D may be of diagnostic value for detection of radiation pneumonitis, even when the radiographic change is faint.

Adult↗
PubMed2001

The homeobox genes vox and vent are redundant repressors of dorsal fates in zebrafish.

Ventralizing transcriptional repressors in the Vox/Vent family have been proposed to be important regulators of dorsoventral patterning in the early embryo. While the zebrafish genes vox (vega1) and vent (vega2) both have ventralizing activity in overexpression assays, loss-of-function studies are needed to determine whether these genes have distinct or redundant functions in dorsoventral patterning and to provide critical tests of the proposed regulatory interactions among vox, vent and other genes that act to establish the dorsoventral axis. We show that vox and vent are redundant repressors of dorsal fates in zebrafish. Mutants that lack vox function have little or no dorsoventral patterning defect, and inactivation of either vox or vent by injection of antisense morpholino oligonucleotides has little or no effect on the embryo. In contrast, embryos that lack both vox and vent function have a dorsalized phenotype. Expression of dorsal mesodermal genes, including chordin, goosecoid and bozozok, is strongly expanded in embryos that lack vox and vent function, indicating that the redundant action of vox and vent is required to restrict dorsal genes to their appropriate territories. Our genetic analysis indicates that the dorsalizing transcription factor Bozozok promotes dorsal fates indirectly, by antagonizing the expression of vox and vent. In turn, vox and vent repress chordin expression, restricting its function as an antagonist of ventral fates to the dorsal side of the embryo. Our results support a model in which BMP signaling induces the expression of ventral genes, while vox and vent act redundantly to prevent the expression of chordin, goosecoid and other dorsal genes in the lateral and ventral mesendoderm.

Animals↗
PubMed2001

Pyrrolo[2,3-d]pyrimidine thymidylate synthase inhibitors: design and synthesis of one-carbon bridge derivatives.

A series of novel pyrrolo[2,3-d]pyrimidine derivatives was designed and synthesized as thymidylate synthase (TS) inhibitors. Molecular design was performed on the human TS complex model built on the basis of the reported structure of TS-deoxyuridinemonophosphate (dUMP)-CB3717 ternary complex. From a docking study, we expected that a one-carbon bridge between pyrrolo[2,3-d]pyrimidine and an aromatic ring was suitable. Moreover, we found that the bridge carbon could be replaced with an alkyl group to fill out the unoccupied space. Based on this design, we synthesized five pyrrolo[2,3-d]pyrimidine derivatives with one-carbon bridge and evaluated their TS inhibitory activities. All synthesized compounds inhibited TS more potently than compound 2 (LY231514), and the C8-ethyl analogue (7) showed a remarkable inhibitory activity against TS (IC50=0.017 microM).

Amino Acid Sequence↗
PubMed2001

Risk factors and predictors of coronary arterial lesions in Japanese hypertensive patients.

The morbidity rate of coronary artery disease has recently increased in Japan. This is attributable to changes from traditional to more westernized lifestyles. In this study, we therefore examined the risk factors and predictors of coronary arterial lesions in Japanese patients with essential hypertension. Coronary angiography was performed in 109 consecutive essential hypertension patients (57 men and 52 women; 66 +/- 8.0 years of age) with either angina pectoris or atypical chest pain, who were chosen from 485 consecutive hypertensive patients in a hypertension clinic in Sendai, Japan. Coronary arterial stenosis of greater than 50% was defined as significant and used as a dependent variable for the multiple regression analysis. Risk factors were defined as factors confirmed to have a causal relationship with coronary arterial lesions, whereas arteriosclerotic complications and hypertensive target organ damage were defined as predictors. Multiple logistic regression analysis was performed using these parameters as independent variables. Of 109 patients, 25 had a coronary arterial stenosis greater than 50%. A smoking habit (odds ratio (OR): 4.48; 95% confidence interval (CI): 1.13-17.82; p<0.05), hypercholesterolemia (OR: 5.34; 95% CI: 1.52-18.73; p<0.05), and 24-h diastolic blood pressure (OR: 2.33; 95% CI: 1.06-5.16; p<0.05) were significant risk factors, whereas carotid intima-media thickness (OR: 5.85; 95% CI: 1.48-23.2; p<0.05) was a significant predictor of coronary arterial lesion. When two of the major risk factors (a smoking habit, hypercholesterolemia, or impaired glucose tolerance including diabetes mellitus) were clustered in addition to the hypertension, the risk of coronary arterial lesions increased by 6.7 to 10.1 times. These findings indicate that the major risk factors established in Caucasians, i.e., a smoking habit, hypercholesterolemia and blood pressure level, are also risk factors for coronary arterial lesions in Japanese with essential hypertension. The presence of two or more risk factors increases the risk of coronary arterial lesions synergistically in the presence of hypertension.

Aged↗
PubMed2001

Characteristics of infertility in female hypothyroid (hyt) mice.

Female hypothyroid (hyt) mice are infertile, but the reason for this infertility is not yet known. The present study was conducted to determine whether hypothyroidism induced infertility in immature and mature hyt mice. Furthermore, animals were treated with thyroxine and gonadotrophins at different times to determine whether infertility was due to failure of follicular development, implantation or pregnancy. There were no significant differences in the numbers of ovulated eggs induced by gonadotrophin treatment or the percentages of eggs developed in vitro among immature normal controls, hyt and thyroxine-treated hyt mice. Mature hyt mice showed continuous dioestrus, and ovulated significantly fewer eggs after gonadotrophin treatment and failed to establish pregnancy after mating compared with mature control mice. Mature hyt mice had significantly fewer corpora lutea > 500 microm in diameter and significantly lower progesterone concentrations. Thyroxine treatment before mating in hyt mice resulted in well-developed corpora lutea, an increase in progesterone and normal pregnancy, regardless of subsequent thyroxine administration. In conclusion, infertility occurs in mature rather than immature hyt mice, is due to the failure of follicular development and pregnancy, and can be reversed by thyroxine treatment before mating.

Animals↗
PubMed2001

Assessment of reflection pulse wave in patients with cardiomyopathy: evaluation of noninvasive measurement of wave intensity.

OBJECTIVE: We assessed the reflection pressure wave using noninvasive measurement of wave intensity (WI) in patients with cardiomyopathy. METHODS AND RESULTS: Subjects included 8 patients with hypertrophic cardiomyopathy (HCM group) and 10 patients with dilated cardiomyopathy (DCM group). Twelve healthy subjects were used as a control group. By using a combined Doppler and echo-tracking system, changes in vascular diameter (dD) and blood flow velocity (dV) were recorded simultaneously at the common carotid artery and dD x dV was measured as WI. In the components of WI, the positive component of early systolic phase (FE) and the negative component following FE (B) were significantly reduced in the DCM group. There was a significant positive correlation between FE and B in all 3 groups. The appearance time of B was significantly shorter in the HCM group and significantly longer in the DCM group compared with the control group. CONCLUSIONS: It was suggested that the value of the reflection pressure wave was influenced by the left ventricular contractility, and that the effect of the reflection pressure wave appeared earlier in patients with HCM and later in patients with DCM compared with the control subjects.

Blood Flow Velocity↗
PubMed2001

An estimation of buffer values of human whole blood by titration experiment under the open condition for carbon dioxide gas.

We studied the buffer mechanism of human whole blood by means of a titration experiment under the open condition in which blood is exposed to carbon dioxide gas. Van Slyke proposed the theory of a blood buffer mechanism in 1922 (J Biol Chem 52: 525-570). However, his theory is not applicable to our experiments because it did not take into consideration the effects of changes in volume and the concentration of bicarbonate ion in the buffer as a result of titration. We studied the blood buffer mechanism theoretically by using graphical representation and developed a theory, which we then applied to our experiments. Buffer value, as defined by Van Slyke, is the quantity of the base deltan(OH)/V in the sample without volume change (in gram equivalent per liter) required to change one unit in pH. Based on our blood buffer theory, we obtain the experimental buffer value betaprime prime or minute, which is the reciprocal slope of the dpH-bdV/V (deltan(OH) in the sample with volume change) relation during a titration experiment at a constant carbon dioxide pressure (pCO(2)) with volume change dV and an isotonic NaOH concentration of b = 0.15 M. The true buffer value beta under physiological conditions is estimated to be beta = deltan(OH)/VdpH = betaprime prime or minute (0.15 minus sign [HCO(3)(minus sign)])/0.15. Here, [HCO(3)(minus sign)] is the concentration of bicarbonate ion in blood that can be calculated by using the Henderson-Hasselbalch equation. We determined the agreement of our experimental results with the theoretical results and estimated the quantity m(A) of the buffer component, except for the bicarbonate buffer, and the dissociation constant K(A) of the buffer reaction in a neutral pH range. The true buffer value of whole blood can be estimated by using our theory and the results of precise experiments.

Acid-Base Equilibrium↗
PubMed2001

Characterization of powder components of commercial bone cements.

Acrylic bone cements have been used in orthopedic surgery without detailed information on their basic characteristics, especially on their powder components. In this study, the powder components of seven bone cements available on the market in Japan were characterized for morphology, polymer structure and molecular weight, content of residual monomer and benzoyl peroxide (BPO), and thermal properties using scanning electron microscopy, nuclear magnetic resonance spectroscopy, size exclusion chromatography, high performance liquid chromatography, and differential scanning calorimetry, respectively. Considerable differences between the seven bone cements were found in polymer structure and molecular weight, and especially in BPO content and in the morphology of the polymer particles such as shape, size and distribution. It was found that the BPO content was not always in agreement with the value given by the manufacturers on the package.

Acrylic Resins↗
PubMed2001

Change in the bisphenol A content in a polycarbonate orthodontic bracket and its leaching characteristics in water.

The change in the bisphenol A (BPA) content in a polycarbonate (PC) orthodontic bracket and its leaching characteristics were studied by immersing the bracket in water because BPA has been the matter of controversy in dentistry due to its estrogenic potential. PC brackets were placed in water at 37 degrees C and 60 degrees C and the BPA content in the bracket and the amount of BPA released into the water were analyzed at appropriate intervals by high performance liquid chromatography. The BPA content increased in the water with time and was 3.8-fold after 12 months at 37 degrees C and 12.4-fold after 14 weeks at 60 degrees C compared with the virgin value. The rate of BPA release also increased with time. The results suggested that BPA was released from the bracket time-dependently in the oral cavity. However, it was assessed that little or no estrogenic effect due to the released BPA is expected in the human body.

Benzhydryl Compounds↗
PubMed2001

Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and myocardial infarction in Japanese. An approach entailing melting curve analysis with specific fluorescent hybridization probes.

The platelet-collagen receptor, glycoprotein Ia/IIa (integrin alpha2beta1) plays a fundamental role in the adhesion of platelets to fibrillar collagen, an event leading to platelet activation and thrombus formation and contributing to the pathogenesis of thrombotic disease. Further, glycoprotein Ia/IIa receptor density and function may be associated with two linked and silent polymorphisms (807C/T and 873G/A) within the glycoprotein Ia gene. We tested the extent to which these polymorphisms serve as genetic markers of myocardial infarction in a Japanese population. A case-control study was carried out using 210 Japanese myocardial infarction patients and 420 age- and sex-matched controls. Genotyping was accomplished using PCR followed by melting curve analysis with specific fluorescent hybridization probes. The 807CC, CT, TT genotypes linked perfectly to the 873GG, GA, AA genotypes, respectively. Allele frequencies of the 807T (873A) variant were similar in the control and patient groups (0.373 vs. 0.352). The 807T and 873A variants of platelet glycoprotein Ia gene are common and in a perfect linkage in the Japanese population, but it appears unlikely that the 807T (873A) variant represents a useful marker of increased risk for myocardial infarction.

Adult↗
PubMed2001

Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer.

Plasma transforming growth factor beta1 (TGF-beta1) has been reported to be correlated with the extent of disease in colorectal cancer, but it is not known whether measuring this cytokine can help predict liver metastasis after curative resection. We prospectively studied whether plasma TGF-beta1 levels could predict liver metastasis in 117 patients with colorectal cancer before and after curative resection. Blood samples were drawn before and 2 weeks after surgery to determine the cytokine levels. Abdominal ultrasonography or computed tomography was done every 3 months after surgery. The primary end point for follow-up was recurrence. Seventy-seven of 117 cases (66%) had preoperative levels of the cytokine higher than the borderline limit of 7.5 ng/ml. Postoperative levels were >7.5 ng/ml in 29 of 117 patients (25%). The median follow-up period was 42 months (range, 5--66 months), with follow-up of all 117 patients. No recurrence was observed in 13 patients with Dukes' stage A lesions. Liver metastasis occurred in 18 of 104 patients (17%) with Dukes' stage B or C disease. Fourteen of 18 patients (78%) who developed liver metastasis had shown a postoperative plasma TGF-beta1 level of >7.5 ng/ml. Cox proportional hazards regression analysis showed that the postoperative level was a significant predictive factor for liver metastasis (P < 0.001). A single point measurement of plasma TGF-beta1 levels at 2 weeks after curative resection seems to be able to predict liver metastasis in colorectal cancer. This finding suggests the value of a prospective trial of liver-targeted adjuvant therapy for patients with elevated postoperative plasma TGF-beta1 levels.

Aged↗