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Biomedical subjects

T Sakamoto

Publications and source records attributed to T Sakamoto.

At least 235 records · Page 13Linked to original sources
PubMed2000

Hypothermia attenuates the vasodilatory response of pial arterioles to hemorrhagic hypotension in the cat.

UNLABELLED: We investigated the effect of hypothermia on the vasodilatory response of pial arterioles to hemorrhagic hypotension. The cranial window technique was combined with microscopic video recording in an experiment involving 20 cats anesthetized with pentobarbital. The animals were randomly assigned to either a normothermic or a hypothermic group (32 degrees C). Mean arterial pressure (MAP) was reduced in stepwise increments of 10 mm Hg (from 100 to 50 mm Hg) by blood withdrawal. The diameter of small (50-100 microm) and large (100-200 microm) pial arterioles was measured. In the normothermic group (n = 9), small and large arterioles dilated at a MAP of 60 and 50 mm Hg, and at a MAP of 70, 60, and 50 mm Hg, respectively, compared with baseline values obtained at a MAP of 100 mm Hg. In contrast, in the hypothermic group (n = 11), vasodilation of either small or large arterioles was absent. The percentage diameter of small and large arterioles (percentage of control) was significantly lower at a MAP of 70, 60, and 50 mm Hg in the hypothermic group than the normothermic group. Our in vivo study demonstrates that hypothermia impairs autoregulatory vasodilation of pial arterioles in response to hemorrhagic hypotension. IMPLICATIONS: Deliberate mild hypothermia has been proposed as a means of providing cerebral protection during neurosurgical procedures. Our results suggest that cerebral blood flow autoregulation in response to hemorrhagic hypotension may be impaired during hypothermic conditions, indicating the importance of maintaining perfusion pressure during hypothermic therapy to prevent cerebral ischemia.

Animals↗
PubMed2000

Surface cooling, which fails to reduce the core temperature rapidly, hastens death during severe hemorrhagic shock in pigs.

OBJECTIVE: To examine whether surface cooling (SC) would rapidly decrease the core temperatures and prolong the survival time during volume-controlled lethal hemorrhagic shock in pigs. METHOD: Twelve pigs were randomly assigned to the SC group (group 1, n = 6) or the no cooling control group (group 2, n = 6), after blood withdrawal of 30 mL/kg over 15 minutes, and maintained under spontaneous breathing by light anesthesia with 1.0% halothane. SC was performed by applying ethanol to the skin, blowing with an electric fan, and placing ice packs. Pigs were observed without fluid resuscitation until their death (apnea and no pulse). RESULTS: SC did not lower the rectal temperature (Tr) to 35 degrees C at any time point until death, except one pig; in that animal, Tr was decreased to 34 degrees C after 135 minutes from the start of SC. The survival time was 108 +/- 43 minutes in group 1 and 175 +/- 55 minutes in group 2 (p < 0.05, life table analysis). CONCLUSION: In lightly anesthetized pigs during hemorrhagic shock, SC without resuscitation did not rapidly reduce the core temperature and rather hastened death for reasons that remain to be explored.

Analysis of Variance↗
PubMed2000

A quantitative analysis of head injury using T2*-weighted gradient-echo imaging.

BACKGROUND: T2*-weighted gradient-echo imaging (T2*-GE) is useful for detecting small hemorrhages. METHODS: Thirty-four patients were prospectively examined, first by magnetic resonance imaging (1.5 T) and then by T2-weighted fast spin echo (T2-FSE) and T2*-GE. Thereafter, the correlations between the T2-FSE or T2*-GE findings and the clinical or computed tomography findings were analyzed. RESULTS: The number of lesions detected by T2*-GE was 14.5 +/- 16.3 (mean +/- SD, n = 34), which was significantly (p < 0.001) greater than that detected by T2-FSE (5.6 +/- 5.6, n = 34). The findings of T2*-GE correlated positively with both the duration of unconsciousness (R2 = 0.74,p < 0.0001) and with Glasgow Outcome Scale (R2 = 0.81, p < 0.0001), whereas those of T2-FSE did not show any significant correlation. T2*-GE imaging could also detect all areas responsible for focal neurologic signs 1 month after in. jury, whereas T2-FSE imaging detected only 22 of 33 such signs. CONCLUSION: T2*-GE was found to be useful for evaluating the clinical symptoms of head injury.

Adolescent↗
PubMed2000

Salivary excretion of N-nitrosodimethylamine in dogs.

Carcinogenic N-nitroso compounds (NOCs) are not only ingested from the environment but are also formed endogenously from precursors. It has been reported that nitrate, an NOC precursor, has an enterosalivary cycle and that the cycle increases the chance of exposure to NOCs. However, there is no information on the salivary excretion of NOCs. In the present study, the toxicokinetics of N-nitrosodimethylamine (NDMA) in dogs was evaluated, focusing on the salivary excretion. Following intravenous injection of 2 mg/kg NDMA, the plasma concentration showed a monoexponential decline, and the total body clearance and apparent distribution volume were greatly in excess of the hepatic plasma flow and total body water, respectively. A high concentration of NDMA was immediately detected in the plasma after oral administration of the same dose, and the oral bioavailability was almost 100%. NDMA was rapidly excreted into the saliva after both treatments, and the concentration in saliva was higher than that in the plasma. These results suggest that NDMA also has an enterosalivary cycle: NDMA is partially excreted from blood into saliva, delivered into the gastrointestinal tract by swallowing the saliva, and then completely reabsorbed into the systemic circulation. This concept was also supported by kinetic analysis based on a compartment model. The enterosalivary cycle of NDMA cannot be ignored in the risk assessment of carcinogenesis.

Animals↗
PubMed2000

Purification of a jojoba embryo wax synthase, cloning of its cDNA, and production of high levels of wax in seeds of transgenic arabidopsis.

Wax synthase (WS, fatty acyl-coenzyme A [coA]: fatty alcohol acyltransferase) catalyzes the final step in the synthesis of linear esters (waxes) that accumulate in seeds of jojoba (Simmondsia chinensis). We have characterized and partially purified this enzyme from developing jojoba embryos. A protein whose presence correlated with WS activity during chromatographic fractionation was identified and a cDNA encoding that protein was cloned. Seed-specific expression of the cDNA in transgenic Arabidopsis conferred high levels of WS activity on developing embryos from those plants. The WS sequence has significant homology with several Arabidopsis open reading frames of unknown function. Wax production in jojoba requires, in addition to WS, a fatty acyl-CoA reductase (FAR) and an efficient fatty acid elongase system that forms the substrates preferred by the FAR. We have expressed the jojoba WS cDNA in Arabidopsis in combination with cDNAs encoding the jojoba FAR and a beta-ketoacyl-CoA synthase (a component of fatty acid elongase) from Lunaria annua. (13)C-Nuclear magnetic resonance analysis of pooled whole seeds from transgenic plants indicated that as many as 49% of the oil molecules in the seeds were waxes. Gas chromatography analysis of transmethylated oil from individual seeds suggested that wax levels may represent up to 70% (by weight) of the oil present in those seeds.

Acyltransferases↗
PubMed2000

Insulin resistance and endothelial dysfunction in smokers: effects of vitamin C.

Cigarette smoking impairs endothelial function and is one of the major risk factors for atherosclerosis and coronary heart disease. Insulin resistance is associated with major risk factors for atherosclerosis. We examined the effects of vitamin C on insulin sensitivity and endothelial function by measuring steady-state plasma glucose (SSPG) and flow-mediated dilation (FMD) of the brachial artery. We studied 16 current smokers with normal glucose tolerance, 15 nonsmokers with impaired glucose tolerance (IGT), and 17 nonsmokers with normal glucose tolerance as controls. Both SSPG and FMD were blunted in smokers and nonsmokers with IGT compared with controls. In smokers, vitamin C decreased SSPG (P < 0.01 by ANOVA) with decreasing plasma thiobarbituric acid-reactive substances (TBARS) (P < 0.05 by ANOVA) and improved FMD (P < 0.05 by ANOVA). Furthermore, vitamin C improved both SSPG (P < 0.005 by ANOVA) and FMD (P < 0.05 by ANOVA) in nonsmokers with IGT. SSPG, FMD, or TBARS in controls did not change after vitamin C infusion. There was a significant correlation between SSPG and FMD both in smokers and nonsmokers with IGT, whereas no correlation was observed in controls. In conclusion, both insulin sensitivity and endothelial function were impaired in smokers and nonsmokers with IGT and were improved by vitamin C. Thus increased reactive oxygen species play an important role in the pathogenesis of insulin resistance as well as endothelial dysfunction in smokers and nonsmokers with IGT.

Analysis of Variance↗
PubMed2000

Increased blood vascular endothelial growth factor levels in patients with acute myocardial infarction.

Vascular endothelial growth factor (VEGF) is a growth factor for vascular endothelial cells in vitro. The present study was designed to determine whether serum VEGF levels increase in patients with acute myocardial infarction (AMI) compared with patients with stable exertional angina and control subjects, and to examine the serial changes of serum VEGF levels in patients with AMI. We examined serum VEGF levels by using antibody prepared from serum immunized with human VEGF(121). The serum VEGF level (pg/ml) was higher (p < 0. 0001) on admission in the patients with AMI (177 +/- 19) than in those with stable exertional angina (61 +/- 7) and control subjects (62 +/- 6). The serum VEGF level (pg/ml) of the patients with AMI was 177 +/- 19 on admission, 125 +/- 9 on day 3, 137 +/- 11 on day 5, 242 +/- 18 at 1 week, and 258 +/- 22 at 2 weeks after admission. The value was higher on admission than on day 3 after admission (p = 0.014), the values were higher at 1 week and 2 weeks than on admission, on day 3, and 5 (p < 0.01). Furthermore, there were correlations between peak VEGF levels at 1 week or 2 weeks after admission and peak creatine kinase levels. The increase of VEGF on admission in the patients with AMI may be due to the hypoxia of acute myocardial ischemia. The elevation at 1 week and 2 weeks from the onset may cause the development of collateral circulation in relation to the healing of the infarction site.

Aged↗
PubMed2000

Epidermal growth factor inhibits 8-Br-cAMP-induced decidualization of human endometrial stromal cells.

The effects of epidermal growth factor (EGF) on human endometrial stromal cells have not been characterized well, although production of EGF in endometrial epithelial and stromal cells and expression of EGF receptors in endometrial stromal cells have been reported. We investigated the effects of EGF on endometrial cell viability, 8-Br-cAMP-induced stromal decidualization, and prolactin secretion from decidualized endometrial stromal cells using an in vitro decidualization activity assay of human endometrial stromal cells. EGF did not show any significant effects on viable cell numbers of nondecidualized and 8-Br-cAMP-induced decidualized cells. Prolactin release from the 8-Br-cAMP-induced decidualized cells was not affected by EGF. However, EGF dose-dependently inhibited prolactin release from the stromal cells that were in the process of decidualization by co-stimulation with 8-Br-cAMP and EGF, though there was no significant change in viable cell numbers of the 8-Br-cAMP-stimulated decidualizing cells. Flow cytometric analysis revealed that 8-Br-cAMP enhanced EGF receptor expression on the endometrial stromal cells. These results indicate that endometrial EGF inhibits decidualization through autocrine/paracrine mechanisms.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Human endometrial stromal interleukin-1 beta: autocrine secretion and inhibition by interleukin-1 receptor antagonist.

Decidualization of human endometrial stromal cells is suppressed by endometrial IL-1 in an autocrine or paracrine manner, indicating that constant suppression of stromal decidualization by IL-1 requires a neutralizing mechanism for IL-1 action to accept embryo implantation. Since production of IL-1ra in human endometrium is reported to be 10- to 30-fold higher than that of IL-1 alpha/beta, we investigated whether endogenous IL-1 beta secreted from human endometrial stromal cells can be inhibited by IL-1ra by using an in vitro decidualization culture. Human stromal cells were cultured with 8-Br-cAMP to induce decidualization, and concentrations of IL-1 beta, IL-8, and prolactin in the culture supernatants were assayed before and after decidualization. There was no significant difference in mean IL-1 beta concentrations measured before and after decidualization. Addition of IL-1ra to endometrial stromal cell cultures strongly inhibited endogenous IL-8 secretion from the cells. Although IL-1 beta showed a biphasic effect on cell proliferation and a suppressive effect on decidualization of stromal cells, these effects were completely inhibited by IL-1ra. The results imply that a high in vivo concentration of IL-1ra in human endometrial tissues may regulate IL-1 effects on decidualization and cell proliferation of human endometrial stromal cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Dislocation of E-cadherin in the airway epithelium during an antigen-induced asthmatic response.

The airway epithelium plays a critical role in asthma. E-cadherin, located on the basolateral side of the epithelial cells, forms adherent junctions. To investigate the role of E-cadherin on the regulation of permeability of molecules and fluid in asthmatic responses, we observed the dynamics of E-cadherin after an immunochallenge against guinea pigs. Immunohistochemical studies revealed that E-cadherin was expressed on the lateral sides of epithelial cells before the immunochallenge and after immediate airway responses (IAR). However, E-cadherin immunoreactivities decreased from the basolateral region in late airway responses (LAR) 6 h after the challenge. Simultaneously, soluble E-cadherin immunoreactivities were detected in lavage fluid only in LAR, suggesting that E-cadherin is partly cleaved and released into the lumen in LAR. Airway permeability, which was examined by penetration of horseradish peroxidase from the airway side into the epithelium, increased in both IAR and LAR. These results suggest that E-cadherin detachment from the lateral side of the epithelial cells increased airway permeability in LAR but not IAR. We conclude that an antigen challenge causes an opening of adherent junctions as well as increases airway permeability in LAR. This mechanism would participate in airflow limitation during attacks and the increase of airway permeability and hyperresponsiveness in asthmatics.

Animals↗
PubMed2000

Precise anatomic configuration changes in the first ray of the hallux valgus foot.

To detect precise anatomical configuration of the first ray in feet with hallux valgus, a two-dimensional coordinate system was devised for evaluation of a weight-bearing dorsoplantar radiograph. The radiographs, taken from 229 feet of 114 patients with symptomatic hallux valgus and 94 normal feet, were investigated. A comparative study showed the first metatarsal head of a foot with hallux valgus was located on the medial side of that of the normal foot and the base of the proximal phalanx of the hallux valgus foot was located on the same point of that of the normal foot. Lateral translation of the base of the proximal phalanx occurred only in cases with overlap toes. Our study shows that subluxation of the metatarsophalangeal joint in hallux valgus is primarily caused by metatarsus primus varus. This study indicated that first metatarsal osteotomies should be given the first priority in consideration for bunion surgery, because these procedures could move the first metatarsal heads laterally in a more normal position.

Adolescent↗
PubMed2000

Functional ureogenesis in the gobiid fish Mugilogobius abei.

To examine the transition to ureogenesis, the gobiid fish Mugilogobius abei was immersed in 2 mmol l(-)(1) NH(4)HCO(3) or a (15)N-labelled ammonia solution [1 mmol l(-)(1) ((15)NH(4))(2)SO(4), pH 8.0] for 4-8 days. When exposed to 2 mmol l(-)(1) NH(4)HCO(3) or (15)N-labelled ammonia solution for 4 days, the rate of urea excretion increased to seven times that of the control (in 20 % synthetic sea water) and remained at this level for 4 days. The proportion of nitrogen excreted as urea reached 62 % of total nitrogen excretion (ammonia-N + urea-N). (15)N-enrichment of the amide-N in glutamine in the tissues of fish exposed to (15)N-labelled ammonia was virtually the same as that of ammonia-N: i.e. approximately twice that of urea-N in the excreta and the tissues. Glutamine contents and glutamine synthetase activities in the liver and muscle increased greatly following exposure to ammonia. Urea and citrulline contents in the muscle and whole body of the exposed fish increased significantly, whereas uric acid contents remained unchanged. Carbamoyl phosphate synthetase III (CPSase III) mRNA expression and CPSase III activity were detected in the muscle, skin and gill, but levels were negligible in the liver. Furthermore, all other ornithine-urea cycle (O-UC) enzymes were also detected in muscle, skin and gill. Thus, M. abei clearly shows the transition from ammoniotely to ureotely under ammonia-loading condition and is able to produce urea mainly via the O-UC operating in multiple non-hepatic tissues as a means for ammonia detoxification.

Amino Acid Sequence↗
PubMed2000

New strong fibrates with piperidine moiety.

New fibrates containing piperidine, 4-hydroxypiperidine, piperidin-3-ene, and piperazine moieties in the structures were synthesized and evaluated. Among the synthesized compounds, 2-[3-[1-(4-fluorobenzoyl)-piperidin-4yl]phenoxyl-2-methylpropanoic acid (9aA: AHL-157) showed very superior activities in decreasing triglyceride, cholesterol, and blood sugar compared to bezafibrate in mice and rats.

Animals↗
PubMed2000

The cyclization reaction of ortho-ethynylbenzaldehyde derivatives into isoquinoline derivatives.

In order to elucidate the reaction mechanism of the cyclization between an ethynyl group and an imino group at the ortho-position on an aromatic ring to afford isoquinolines, reaction of 2-ethynylbenzaldehydes under various conditions was examined. It is concluded that reaction proceeds via an ionic process and the isoquinoline 4-hydrogen atom derives from the solvent. In addition, it was found that 2-ethynylbenzaldehyde O-methyloximes underwent cyclization in the presence of primary and secondary alcohols to give 3-substituted isoquinolines.

Benzaldehydes↗
PubMed2000

New antifungal 1,2,4-triazoles with difluoro(heteroaryl)methyl moiety.

New 1,2,4-triazoles (1) having a difluoro(heteroaryl)methyl moiety were designed and synthesized via 1-aryl-2,2-difluoro-2-(heteroaryl)ethanones (2), which were prepared by two routes starting from the reaction of ethyl 2,2-difluoro(heteroaryl)acetate with phenyllithiums (Route A) and from the reaction of chlorodifluoro(heteroaryl)methane with benzaldehydes (Route B). The compounds 1 except for 1g show antifungal activities against yeasts and filamentous fungi in vitro, especially (+)-1f have equal or superior activities compared to those of itraconazole.

Antifungal Agents↗
PubMed2000

Elevated levels of soluble intercellular adhesion molecule-1 in the coronary circulation of patients with coronary organic stenosis and spasm.

The cell surface expression of intercellular adhesion molecule-1 (ICAM-1) is upregulated following activation during inflammatory responses, mediating both cell migration and activation. The involvement of inflammation in unstable angina is suggested by the presence of activated circulating leukocytes. To examine whether plasma soluble ICAM-1 (sICAM-1) levels increase in the coronary circulation of patients with coronary organic stenosis and coronary spasm, plasma sICAM-1 levels were measured in the coronary sinus (CS) and the aortic root (Ao) simultaneously in 10 patients with 90% or more coronary narrowing and coronary spasm (coronary spastic angina (CSA) with organic stenosis), in 11 patients with coronary spasm and no significant coronary narrowing (CSA without organic stenosis), in 16 patients with stable exertional angina, and in 13 control subjects. The plasma sICAM-1 levels (ng/ml) in the CS increased in CSA with organic stenosis (230+/-26) as compared with CSA without organic stenosis (158+/-14), stable exertional angina (130+/-9) and control subjects (121+/-10) (p<0.01). The levels in the Ao also increased in CSA with organic stenosis (208+/-24) as compared with CSA without organic stenosis (149+/-13), stable exertional angina (130+/-11) and control subjects (121+/-10) (p<0.01). Furthermore, the plasma sICAM-1 levels were higher in the CS than in the Ao only in CSA with organic stenosis. These results suggest that activation of leukocytes occurs through the induction of ICAM-1 in the coronary circulation in the patients with CSA with organic stenosis.

Aged↗
PubMed2000

Increased rate of formation of small-sized platelet aggregates in patients with acute coronary syndromes.

Coronary thrombosis has been implicated in the pathogenesis of acute coronary syndromes, and platelet activation plays a pivotal role in the pathogenesis of coronary thrombus. A new platelet aggregometer using a laserlight scattering beam was trialled for assessment of platelet aggregation. Platelet aggregability, especially small-sized platelet aggregates, was investigated on admission using the laser-light scattering method and again after treatment in 23 patients with acute coronary syndromes. The platelet aggregability in 14 patients with stable exertional angina and in 14 control subjects was also examined. On admission, the number of small- and medium-sized platelet aggregates in the acute coronary syndromes group was significantly greater than in the stable exertional angina group or control group. However, the number of large-sized platelet aggregates on admission was not increased in the acute coronary syndromes group. Furthermore, the number of small- and medium-sized platelet aggregates decreased significantly after treatment in the acute coronary syndromes group. The increased number of small-sized platelet aggregates may sensitively reflect attacks of thrombosis in patients suffering acute coronary syndromes.

Acute Disease↗