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Biomedical subjects

H Saito

Publications and source records attributed to H Saito.

At least 91 records · Page 5Linked to original sources
PubMed2002

Dual adrenergic control of in vivo choline levels in the mouse major salivary glands.

1. The purpose of this study was to demonstrate that the adrenergic nervous system regulates the in vivo choline levels in the mouse major salivary glands. 2. Methoxamine (alpha1-adrenoceptor agonist, 2.5-20 mg kg-1, s.c.) elevated choline levels dose-dependently and the effect of methoxamine (10 mg kg-1) was completely inhibited by the alpha-adrenoceptor antagonist phentolamine (5 mg kg-1, i.p.) but not by the beta-adrenoceptor antagonist propranolol (3 mg kg-1, i.p.). 3. In contrast, isoprenaline (beta-adrenoceptor agonist 0.25-20 mg kg-1, s.c.) lowered choline levels and the effect of isoprenaline (2 mg kg-1) was inhibited by propranolol, but not by phentolamine. 4 Noradrenaline (1-4 mg kg-1, s.c.) manifested both the alpha- and beta-adrenergic actions depending on its dose. Noradrenaline at 1-2 mg kg-1, lowered choline levels and the effect of noradrenaline (1 mg kg-1) was inhibited by propranolol, but not by phentolamine. On the other hand, noradrenaline (4 mg kg-1) elevated choline levels and the effect was blocked by phentolamine, but not by propranolol. 5. Tyramine (5-80 mg kg-1, s.c.) elicited the release of noradrenaline from sympathetic nerve terminals and induced essentially the same effects on the choline levels as noradrenaline. Tyramine (10 mg kg-1) lowered choline levels and the effect was inhibited by propranolol, but not by phentolamine. However, tyramine (80 mg kg-1) elevated choline levels and the effect was inhibited by phentolamine, but not by propranolol. 6. These results suggest that choline levels in the salivary glands may be under separate alpha- and beta-adrenergic control and suggest a possibility that the neurotransmitter noradrenaline released for sympathetic nerve terminals can manage the dual control of choline levels in some autonomic organs in a characteristic dose-dependent manner.

Adrenergic Agonists↗
PubMed2002

Biopsy pathology predicts patients with ulcerative colitis subsequently requiring surgery.

BACKGROUND: The clinical course of patients with ulcerative colitis (UC) is unpredictable, and 17%-38% ultimately require surgery. We hypothesized that mucosal histology may differ between patients requiring surgery and those receiving medication alone. The aim of this study was to elucidate comprehensive criteria consisting of specific histologic features enabling the prediction of failure to medical treatment. METHODS: We studied colorectal biopsy specimens from 67 patients ultimately requiring surgery (UC-S) and 90 receiving medication alone for more than 3 years (UC-M), and conducted multiple logistic regression analysis on 70 histologic features together with endoscopic disease extent and patient age. The analysis constructed an equation finding probability of UC-S (P(UC-S)). Based on a receiver-operating characteristic curve, we selected four cut-off values of P(UC-S), and determined criteria of five categories: highest-risk, higher-risk, unpredictable, lower-risk and lowest-risk of surgery. Sensitivity and specificity of criteria were evaluated in a 2 x 5 table. RESULTS: Statistically significant features predicting UC-S were deep ulceration (X1), frequent crypt abscesses (X2), focal and segmental mononuclear cell infiltration (X3 and X4), paucity of eosinophils (X5: eosinophil infiltration) and wide extent of the disease (X6). The regression equation was as follows: logitP(UC-S) = -16.26 + 3.20X1 + 4.83X2 + 11.65X3 + 5. 10X4 - 5.59X5 + 5.53X6. Higher-risk and lower-risk showed sensitivity exceeding 91.0% and specificity exceeding 98.5% in predicting the outcome. CONCLUSIONS: Our criteria incorporating specific histologic features and endoscopic disease extent reliably predict eventual clinical outcome, and are expected to prove useful in determining the necessity of surgery.

Adult↗
PubMed2002

Pharmacokinetic evaluation of high pulmonary disposition of clarithromycin after systemic administration.

1. The distribution characteristics of clarithromycin to the lung were investigated in vivo and in isolated lung perfusion experiments. The in-vivo integration plot analysis showed that the pulmonary uptake and extracellular distribution in the lung were significantly higher for clarithromycin than for erythromycin. 2. In the rat lung single-pass perfusion study, the pulmonary extraction ratio (E(ss)) of clarithromycin at steady-state was significantly higher than that of erythromycin, and the E(ss) of clarithromycin tended to decrease as the inflow concentration increased, suggesting the involvement of carrier-mediated transport in the pulmonary disposition of clarithromycin. 3. The outflow patterns of clarithromycin or erythromycin at various inflow concentrations were simultaneously analysed based on a pharmacokinetic model, which consists of the non-specific binding site, the specific binding site and the subsequent uptake process. The parameters obtained suggested that clarithromycin would have the higher affinity and higher capacity for the specific binding site, and the higher equilibrium constant for the non-specific binding site than erythromycin. 4. The simulation study using those parameters demonstrated that clarithromycin could be bound to the specific binding site and subsequently taken up more extensively than erythromycin. 5. A multiple-indicator dilution study also indicated that clarithromycin was more readily associated and extracted with the lung than with erythromycin. In the inhibition study, it was suggested that the pulmonary uptake of clarithromycin could be ascribed not only to the non-specific binding depending on its lipophilic nature, but also in part to some specialized mechanisms such as organic cation transporters.

Animals↗
PubMed2002

Changes in shell membranes during the development of quail embryos.

The shell membrane of an avian egg acts as a bag enclosing albumen and water. At its interface with the albumen, a smooth layer of homogeneous, dense material called the limiting membrane demarcates the shell membrane. The present study aimed to investigate changes in the limiting membrane during development of quail embryos that were grown with or without being turned. Sixty-three percent of the embryos were hatched after the eggs were incubated at 39 C and in 60% humidity with automatic rotation around their long axis and with their equatorial side down, whereas the hatch rate decreased to 24% when the eggs were incubated without being turned. The width of the limiting membrane at the equatorial region of turned eggs gradually decreased from 74 nm on Days 0 to 2 of incubation to 35 nm on Day 10 and thereafter. Conversely, water permeability, measured by evaporation through the shell membrane increased from 4 to 5 nL/mm2 per min on Days 0 to 6, to 9 nL/mm2 per min on Day 12 and thereafter. In stationary eggs, the decrease in the width of the limiting membrane on the lower side of eggs was delayed until Day 8 of incubation. The water permeability of the shell membrane in this group was 51% of that of the membrane on the upper side of eggs on Day 8 of incubation. Forty to forty-four nanometers seemed to be the critical width of the limiting membrane at which high water permeation could occur. It was also shown that the albumen hinders water permeation through the membrane. These results show that (1) the limiting membrane is made thin during the development over the whole surface with egg-turning, possibly through digestion of still unknown agents, and (2) this thinning accelerates the rate of water permeation through the membrane.

Animals↗
PubMed2002

Behavioural and pharmacological relevance of stroke-prone spontaneously hypertensive rats as an animal model of a developmental disorder.

The present study evaluates juvenile stroke-prone spontaneously hypertensive rats (SHRSP) as an animal model of a developmental disorder, which is diagnosed according to hyperactivity-impulsivity and/or inattention. To characterize behavioural alterations, we studied motor activity, as well as emotional and cognitive behaviours in juvenile SHRSP, with and without methylphenidate, a psychostimulant. Ambulatory and rearing activities in the open-field environment were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY). In the elevated plus maze task, the entries into open arms, as an index of impulsivity, were significantly increased in SHRSP. In the Y-maze task, spontaneous alternation behaviour, as an index of attention, was significantly lowered in the male SHRSP, but not in the female SHRSP, indicating that spontaneous alternation deficit is gender specific. Methylphenidate (0.01-1 mg/kg, i.p.) significantly attenuated locomotor hyperactivity at low doses and dose-dependently improved the spontaneous alternation deficit in SHRSP. Our findings reveal that juvenile SHRSP manifest problematic behaviours resembling a developmental disorder, attention-deficit/hyperactivity disorder (ADHD), namely hyperactivity-impulsivity and/or inattention. Methylphenidate alleviated the behavioural symptoms of hyperactivity and inattention. We propose that juvenile SHRSP are an appropriate animal model of a developmental disorder resembling ADHD, from behavioural and pharmacological perspectives.

Animals↗
PubMed2002

[Clinical study of double primary cancer involving the lung in resected cases].

Among all cases of surgically resected lung cancer, there were 56 cases (16.1%) of double primary cancer. The common sites of the other primary cancer was the stomach (19 cases), followed by large intestine (9 cases), urinary bladder (7 cases) and pharinx-larynx (7 cases). One patient had triple cancers. In all cases of double primary cancer, 46 cases were metachronous, 10 of which were cases of initial lung cancer. The 5-year survival rate of double primary cancer was 39.7%. Good result was obtained in metachronous cases with initial lung cancer. Most of prognosis of double primary cancer was determined by that of lung cancer. In more than half of initial cancer, the second primary cancer was detected by symptoms. So, special attention to the possibility of double primary cancer in patients with resected lung cancer is necessary for improvement of prognosis.

Aged↗
PubMed2002

Comparison of emptying between gastric and colonic conduits following esophagectomy.

The emptying of gastric and colonic conduits following esophagectomy was evaluated. Ten consecutive patients who underwent esophagectomy for malignant diseases were divided into two groups as follows: Group I which consisted of 5 patients who underwent pyloroplasty and in whom the gastric greater curvature was used for reconstruction; and Group II which consisted of 5 patients in whom the colonic conduit was used because of previous gastrectomy. The conduits were placed in the retrosternal spaces in all the patients. The radiopaque markers swallowing test and digestive tract scintigraphy were performed to evaluate emptying two months after surgery. The radiopaque markers swallowing test demonstrated that marker rings quickly disappeared from the gastric conduits but remained in the colonic conduits for as long as three hours. Digestive tract scintigraphy demonstrated that there was no significant difference in the 60-minute clearance rate of 99mTc-DTPA from the conduits between the two groups. The results suggested that tiny food fragments remained in the haustral pockets of the colonic conduits, which may be a disadvantage of these conduits.

Aged↗
PubMed2002

[Effect of interleukin-1beta on aromatase activity in human osteoblast-like cells].

OBJECTIVE: To study the stimulation of interleukin (IL)-1beta and interleukin-1 receptor antagonist (IL-1ra) on aromatase activity in human osteoblast cells. METHODS: In the present study, the effect of IL-1beta and IL-1ra on aromatase (Arom) activity and mRNA expression in human osteoblast-like cells was investigated by [(3)H] water released upon the conversion of [1beta-(3)H] androstenedione to estrone and the reverse-transcription polymerase cain reaction (RT-PCR) method. The experimental group is divided into four group: G1 (IL-1beta 1 microgram/L), G2 (10 microgram/L), G3 (IL-1beta 10 microgram/L + IL-1ra 500 microgram/L) and G4 (IL-1ra 500 microgram,/L). RESULTS: The activity of G1 and G2 resulted in (4 211 +/- 348) pmol/10(6) cell.h(-1) and (4 958 +/- 231) pmol/10(6) cell.h(-1), respectively. IL-1ra neutralized the increased arom activity to control level in G3 (3 652 +/- 203) pmol/10(6) cell.h(-1). Arom mRNA expression was increased with the dose increasing of IL-1beta. CONCLUSION: These findings suggest that IL-1beta stimulates arom activity through the IL-1 receptor and addition of IL-1beta increased arom activity in a dose-dependent manner.

Aromatase↗
PubMed2001

Accounting for source location and transport direction into geostatistical prediction of contaminants.

This paper presents a variant of the well-known kriging with a trend that allows one to account for the pollutant source coordinates and information about transport process into the spatial prediction of pollutant concentration. The new technique is illustrated using lead data from a Dallas metropolitan area and cadmium data from Palmerton (PA) NPL Superfund site. Instead of modeling the local spatial trend as low-order polynomials of coordinates, it is here expressed as a function of two factors that likely control the pollution spread: the distance to the smelter and the deviation from the major wind direction. Four different combinations of these two factors are developed, and their prediction performances are evaluated for a range of wind directions using cross-validation. Comparison with two traditional algorithms (OK and KT) shows that the proposed approach leads to smaller mean square errors of prediction when the correct wind direction is determined. The best combination of trend model and wind direction is site-dependent and derived using cross-validation. Kriging of residuals from a global trend model is an alternative to the use of local trends, and both techniques are shown to outperform ordinary kriging.

Algorithms↗
PubMed2001

Homolytic carbostannylation of alkenes and alkynes with tributylstannyl enolates.

In the presence of AIBN, tributylstannyl enolates derived from aromatic ketones reacted with electron-deficient alkenes and a variety of alkynes to give the corresponding carbostannylated adducts. The reactions with methyl acrylate gave alpha-tributylstannylmethyl-gamma-ketoesters, unlike the known Michael-type reaction of stannyl enolates forming delta-ketoesters. The carbostannylation of alkynes proceeded in an anti addition mode to afford beta,gamma-unsaturated ketones. The reactivity of stannyl enolates as radical transfer agents could be utilized for radical cyclization of 1,6-enynes.

Journal Article↗
PubMed2001

Transport characteristics of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2.

Transport characteristics of grepafloxacin and levofloxacin across the apical membrane of Caco-2 cells were examined. Both grepafloxacin and levofloxacin uptakes increased rapidly, and were temperature-dependent. Grepafloxacin and levofloxacin uptakes showed concentration-dependent saturation with Michaelis constants of 3.9 and 9.3 mM, respectively. Uptake of grepafloxacin and levofloxacin increased in Cl(-)-free and ATP depleted conditions, suggesting the involvement of an efflux transport system different from the uptake mechanism. However, cyclosporin A, a typical inhibitor of P-glycoprotein, did not affect the uptake of these drugs. Unlabeled grepafloxacin, unlabeled levofloxacin and quinidine inhibited the uptake of grepafloxacin and levofloxacin under Cl(-)-free conditions. Tetraethylammonium, cimetidine, p-aminohippurate, probenecid, amino acids, beta-lactam antibiotic or monocarboxylates did not inhibit the uptake of grepafloxacin and levofloxacin under the same conditions. In conclusion, our results suggested that grepafloxacin and levofloxacin uptakes were mediated by a specific transport system distinct from those for organic cations and anions, amino acids, dipeptides and monocarboxylates.

Adenosine Triphosphate↗
PubMed2001

Gene expression profiles for Fc epsilon RI, cytokines and chemokines upon Fc epsilon RI activation in human cultured mast cells derived from peripheral blood.

Mast cells have been reported to release not only chemical mediators, but also cytokines upon Fc epsilon receptor I(Fc epsilon RI) cross-linking. Recently, we have established a culture system to derive chymase-rich human mast cells from mononuclear cells in peripheral blood. However, the functional properties of these mast cells have remained unrevealed. In this study, we examined the functions of peripheral blood-derived human cultured mast cells (pHCMCs). pHCMCs expressed functional Fc epsilon RI, and most of them contained tryptase. These pHCMCs sensitized with immunoglobulin E (IgE) and interleukin 4 (IL-4) were activated through cross-linking of Fc epsilon RI. The time-dependent mRNA expression profiles of Fc epsilon RI subunits, cytokines and chemokines in the sensitized pHCMCs upon Fc epsilon RI engagement were examined by reverse transcriptase polymerase chain reaction (RT-PCR). mRNA for most of cytokines and chemokines, which were observed in allergic inflammation, was detected in activated pHCMCs. In addition, gene expression for monocyte chemoattractant protein 3 (MCP-3) in human mast cells, and liver and activation-regulated chemokine (LARC), thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in mast cells was revealed for the first time in our study. Fc epsilon RI-mediated cytokine and chemokine production at protein level was evaluated using enzyme-linked immunosorbent assay (ELISA). These data suggest that pHCMCs, which are capable of producing a variety of cytokines and chemokines, can be a useful candidate for investigating roles of mast cells as a conductor for allergic inflammation.

Cells, Cultured↗
PubMed2001

Systemic administration of lentinan, a branched beta-glucan, enhances long-term potentiation in the rat dentate gyrus in vivo.

We investigated the effects of oral and intravenous application of lentinan, a branched beta-glucan, on the induction of long-term potentiation (LTP) in the rat dentate gyrus in vivo. Oral administration of lentinan (200 mg/kg) enhanced the induction of LTP evoked by sub-threshold tetanic stimulation (20 pulses at 60 Hz) of the perforant pathway without affecting normal synaptic potentials. Intravenous injection of the compound (0.2-10.0 mg/kg) also enhanced the induction of LTP in a bell-shaped manner, whereas it had no effect on LTP evoked by supra-threshold tetanic stimulation (100 pulses at 100 Hz). Structurally related beta-glucans did not mimic the lentinan-triggered enhancement of LTP. These results suggest that peripherally applied lentinan facilitates the synaptic efficacy of the dentate gyrus neurons in vivo.

Adjuvants, Immunologic↗
PubMed2001

Expression of sodium/proton antiporter NhaA at various pH values in Escherichia coli.

It was reported that NhaA, one of sodium/proton antiporters in Escherichia coli, was expressed at alkaline pH [J. Biol. Chem. 266 (1991) 21753]. In disagreement with their results, expression of an nhaA-lacZ fusion gene was found to be very low in an E. coli strain derived from MC4100 within the wide pH range from 5 to 9. When nhaB was deleted, the fusion gene was expressed at pH values below 8, while the expression was observed at alkaline pH after chaA was deleted. The internal level of sodium ions was increased by deletion of nhaA in strains deficient in nhaB and chaA at low and high pH values, respectively. These results suggested that nhaA is induced only when a low level of internal sodium ions is not kept by NhaB and ChaA. Strains used in the previous study may have low active ChaA.

Bacterial Proteins↗
PubMed2001

Identification of Nash1, a novel protein containing a nuclear localization signal, a sterile alpha motif, and an SH3 domain preferentially expressed in mast cells.

By using a serial analysis of gene expression (SAGE), we have identified a novel full-length cDNA that is preferentially expressed in human cord blood-derived mast cells. The predicted protein showed unique primary structure with a nuclear localization signal (NLS), a sterile alpha motif (SAM), and a Src homology 3 domain (SH3) (termed Nash1). Nash1 was mapped to human chromosome 21q11.1 and highly expressed in spleen, liver, peripheral blood, and mast cell lines. In consistent with the presence of NLS, Nash1 was localized in the nucleus. Interestingly, screening gene databases for Nash1-related sequences revealed the existence of a Nash1-related gene termed SLY that was preferentially detected in lymphoid cells. We also found at least two additional candidates for this gene family in the database. These findings suggested that Nash1 and Nash1-related proteins consisted of a novel family of signaling/adaptor proteins, and Nash1 might function as a signaling component of mast cells, possibly in the nucleus.

Adaptor Proteins, Vesicular Transport↗
PubMed2001

Is frozen section effective for diagnosis of unsuspected gallbladder cancer during laparoscopic cholecystectomy?

BACKGROUND: Although frozen section is recommended to prevent tumor dissemination following laparoscopic cholecystectomy (LC) for unsuspected gallbladder cancer, there are no reports concretely demonstrating its effectiveness and outcome. METHODS: Frozen section during LC was performed in 990 patients with gallstones. The sensitivity, specificity of frozen section, and false-negative cases were evaluated in comparison with postoperative entire cross sections. RESULTS: In frozen section, 983 cases were diagnosed as benign and 7 cases as malignant. Of the benign cases, cancer was discovered in 4 patients postoperatively in which frozen section was diagnosed as regenerative epithelial severe atypia. Sensitivity was 64% and specificity was 100%. Concerning the results of frozen section by p-TNM classification, cancer was diagnosed in 40% of Tis lesions, whereas it was found in 83% of T2 or T3 lesions. CONCLUSION: Frozen section is effective in cases with T2 or greater lesions for which conversion to radical surgery should be required.

Adult↗
PubMed2001

Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway.

The Slit protein guides neuronal and leukocyte migration through the transmembrane receptor Roundabout (Robo). We report here that the intracellular domain of Robo interacts with a novel family of Rho GTPase activating proteins (GAPs). Two of the Slit-Robo GAPs (srGAPs) are expressed in regions responsive to Slit. Slit increased srGAP1-Robo1 interaction and inactivated Cdc42. A dominant negative srGAP1 blocked Slit inactivation of Cdc42 and Slit repulsion of migratory cells from the anterior subventricular zone (SVZa) of the forebrain. A constitutively active Cdc42 blocked the repulsive effect of Slit. These results have demonstrated important roles for GAPs and Cdc42 in neuronal migration. We propose a signal transduction pathway from the extracellular guidance cue to intracellular actin polymerization.

Actins↗