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Biomedical subjects

K Yoshimura

Publications and source records attributed to K Yoshimura.

At least 217 records · Page 12Linked to original sources

Association between dopamine D4 receptor (D4DR) exon III polymorphism and novelty seeking in Japanese subjects.

This study was designed to assess the association between novelty seeking and D4DR gene polymorphism in the Japanese population. The 48 bp repeat polymorphism in the third exon of the dopamine D4 receptor gene of 153 normal female students was correlated with personality feature results from the Japanese version of Cloninger's Temperament and Character Inventory. The Novelty Seeking subscale of Exploratory Excitability had a significant association with long alleles of the polymorphic exon III repeat sequence of D4DR. Our results suggest that there is an association between long alleles of the polymorphic exon III repeat sequence of D4DR and the personality traits of the Novelty Seeking subscale of Exploratory Excitability, regardless of racial differences in the frequencies of D4DR exon III repeat polymorphism.

Adolescent↗

Eosinophil adhesion regulates RANTES production in nasal epithelial cells.

Among the many known chemotactic factors for eosinophils, the proinflammatory chemokine RANTES is particularly important, because it is potently and selectively chemotactic for eosinophils. Throughout the process of the migration of eosinophils from the blood vessels into the nasal cavity, eosinophil functions are assumed to be regulated by surface adhesion molecules. Conversely, the messages conferred by the eosinophils to the endothelial and epithelial cells are also of great interest. In the present study, we showed that eosinophil adhesion to human nasal epithelial cells (HNECs) inhibits RANTES production in HNECs. Eosinophils were isolated from peripheral blood obtained from patients with allergic rhinitis. Human mucosal microvascular endothelial cells and HNECs were isolated from human nasal mucosa specimens. After stimulation of the HNECs in the presence of eosinophils, the secretion of RANTES, induced by a combination of TNF-alpha and IFN-gamma, appeared to have decreased. The amount of the decrease was a function of the number of involved eosinophils. On the other hand, the presence of eosinophils did not affect RANTES production by the endothelial cells. After pretreatment of the eosinophils with anti-CD18 mAb or coculture with HNECs in Transwell culture inserts, these cells did not inhibit the TNF-alpha- and IFN-gamma-induced RANTES production. These results were virtually identical with those observed on RANTES mRNA expression. The adhesion of eosinophils to HNECs plays a key role in the inhibition of RANTES production. Our data indicate that a certain established system causes the signal transfer from eosinophils to HNECs to inhibit RANTES production, thus decreasing the eosinophil infiltration.

Adult↗

Potentiation by DSP-4 of EEG slowing and memory impairment in basal forebrain-lesioned rats.

The effects of cholinergic and noradrenergic depletion, alone and in combination, on spatial memory and electroencephalogram (EEG) activity were investigated. Basal forebrain-lesioned rats exhibited a significant decrease in cortical choline acetyltransferase activity and spatial memory impairment. In the cortical EEG, the basal forebrain lesion induced EEG slowing such as an increase in delta power activity and a decrease in beta power activity. Noradrenergic depletion following a treatment with DSP-4 (N-2-(chloroethyl)-N-ethyl-2-bromobenzylamine) had no effect on cortical choline acetyltransferase activity and spatial memory, but it aggravated the cognitive impairment induced by the basal forebrain lesion. DSP-4 itself increased delta power activity in non-lesioned rats, whereas DSP-4 potentiated the EEG slowing induced by the basal forebrain lesions. Systemic administration of tetrahydroaminoacridine at 1 or 3 mg/kg, i.p., ameliorated the memory deficits and EEG slowing induced by the basal forebrain lesion. However, the drug could not attenuate the EEG slowing and memory impairment in rats that had received a combination of DSP-4 and basal forebrain lesion. These results suggest that noradrenergic depletion aggravated the EEG slowing and the spatial memory impairment induced by cholinergic dysfunction and may decrease the efficacy of an anticholinesterase agent in reversing the cortical cholinergic hypofunction.

Animals↗

Conversion of beating mode in Chlamydomonas flagella induced by electric stimulation.

Electric stimulation of a single Chlamydomonas cell by means of a suction electrode induced a temporary conversion of flagellar waveform from an asymmetric forward mode to a symmetric reverse mode. The reverse mode continued for about 0.5 seconds, after which the forward mode was resumed. Anodic stimulation (current passing outward through the membrane outside the suction pipette) was more effective in inducing the flagellar response than cathodic stimulation. No flagellar response was induced in the absence of free Ca2+ or in the presence of calcium channel inhibitors, pimozide (5 microM) and diltyazem (0.3 mM). These findings indicate that the flagellar response by membrane depolarization followed by a Ca2+ influx through voltage-dependent calcium channels. This experimental system allowed us to quantitatively analyze the behavior of flagella during the waveform conversion. The flagellar bending pattern quickly changed from the forward mode to the reverse mode and, thereafter, gradually resumed the forward mode through two discrete phases: changes during reverse mode beating (phase I) and a distinct transitional phase (phase II). Recovery in curvature and sliding velocity of principal bends occurred mostly in phase I. Almost all of the recovery of reverse bends, returning the curvature to the low values characteristic of asymmetric forward mode beating, occurred in phase II. Beat frequency recovered through both phases. Phase II was often interrupted by a temporary stoppage of beating. These findings indicate that the bending pattern is converted through multiple steps that are controlled by Ca2+.

Animals↗

Characterization of protein components of human urinary crystal surface binding substance.

We previously extracted crystal surface binding substance (CSBS) from human urine and showed that it appeared to constitute a substantial proportion of urinary macromolecular inhibitors of calcium oxalate crystallization. CSBS was isolated from human urine and fractionated by three consecutive chromatography procedures in order to characterize protein inhibitors of calcium oxalate crystallization. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and NH2-terminal amino acid sequencing revealed that inhibitory fractions eluted from a final, hydroxyapatite column contained prothrombin and osteopontin. Hydroxyapatite column fractions also contained other, unidentified protein inhibitors of calcium oxalate crystallization. CSBS contained also human serum albumin, alpha 1-acid glycoprotein, alpha 1-microglobulin, alpha 2-HS glycoprotein, retinol-binding protein, transferrin, and Tamm-Horsfall protein, but these proteins seemed to play no direct role in inhibitory activity.

Adult↗

Cytokine responses in mice infected with Angiostrongylus cantonensis.

For determination of the kinetics of cytokine production and its possible role in host resistance to Angiostrongylus cantonensis in the mouse, Th1 [interleukin 2 (IL-2) and interferon gamma (IFN-gamma] and Th2 (IL-5 and IL-4) cytokine production in the cerebrospinal fluid (CSF), sera, and culture supernatants of spleen cells (SC) or cervical lymph-node cells (CLNC) of infected BALB/c and C57BL/6 mice was assessed by a sandwich enzyme-linked immunosorbent assay (ELISA). IL-5 and IL-4 were detected in CSF of both strains, with a peak response occurring at around days 12-15 and 20 postinfection (p.i.), respectively. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay also revealed prominent IL-5 and IL-4 mRNA expression in T-cells but not in eosinophils in CSF. SC and CLNC stimulated with A. cantonensis young adult-worm antigen released IL-5 in vitro at and after day 20 p.i. Contrarily, IFN-gamma production in CSF and SC or CLNC culture supernatants was almost negligible before day 30 p.i. IL-5, IL-4, and IL-2 production in culture supernatants was rather prominent in resistant C57BL/6 mice as opposed to susceptible BALB/c mice as assessed by the magnitude of increase over preinfection levels. Antigen-specific IgG1 (but not IgG2a) responses were more prominent in C57BL/6 mice than in BALB/c mice. These data suggest that systemic and local Th2 cytokine responses, especially those involving IL-5, are predominant in A. cantonensis-infected mice and that IL-5 is an important cytokine underlying the innate resistance of the mouse against A. cantonensis.

Angiostrongylus cantonensis↗

Eosinophilia and intracranial worm recovery in interleukin-5 transgenic and interleukin-5 receptor alpha chain-knockout mice infected with Angiostrongylus cantonensis.

We infected interleukin-5 (IL-5)-transgenic (IL-5-Tg) and IL-5 receptor alpha knockout (IL-5R alpha -/-) mice with Angiostrongylus cantonensis to determine the possible roles of IL-5 and eosinophils in A. cantonensis infection in mice. IL-5-Tg mice demonstrated significantly higher eosinophilia in bone marrow, blood and cerebrospinal fluid (CSF), lower intracranial worm recovery and smaller female worms than naive C3H/HeN mice. Both IL-5-Tg and C3H/HeN mice evoked antigen-specific serum and CSF IgA antibody responses as early as days 5 and 7 postinfection, respectively. Prominent eosinophil infiltration was noted around intracranial worms in the subarachnoid spaces of the mouse brains; eosinophils adhering to the worm surface were degranulated. In contrast, IL-5R alpha -/- mice yielded a higher worm recovery than wild-type or heterozygous mice at day 20 postinfection and failed to provoke CSF eosinophilia. These findings indicate that A. cantonensis infection in the mouse causes IL-5 production and subsequent CSF eosinophilia, the latter probably being involved in the killing of intracranial worms.

Angiostrongylus cantonensis↗

Efficacy of prophylactic sclerotherapy in patients with hepatocellular carcinoma and varices negative for the red color sign.

BACKGROUND: A prospective randomized controlled study was performed to evaluate the usefulness of prophylactic endoscopic sclerotherapy in patients with hepatocellular carcinoma complicated by esophageal varices. METHODS: The subjects included 58 patients with esophageal varices negative for the red color sign and hepatocellular carcinoma without tumor emboli in the portal trunk or primary portal branches. Patients were randomly assigned to prophylactic sclerotherapy (n = 29) or control (n = 29) groups, and their bleeding and survival rates were compared. RESULTS: A mean of 3.0 sclerotherapy sessions was required for complete disappearance of varices in patients receiving prophylactic sclerotherapy. During the observation period, transcatheter arterial embolization for hepatocellular carcinoma was performed more often in patients with prophylactic sclerotherapy (mean 3.8 times) than in control patients (mean 2.0 times) (p < .05). Percutaneous ethanol injection therapy was performed more often in patients with prophylactic sclerotherapy than in controls (mean 8.1 times vs 5.0 times, respectively) (p < .05). The 3-year bleeding rates were 50% for the control group and 18% for the prophylactic sclerotherapy group (p < 0.05), and the 3-year survival rates were 16% for the control group and 37% for the therapy group (p < 0.05). CONCLUSIONS: Prophylactic sclerotherapy improves survival in patients with hepatocellular carcinoma complicated by red color sign-negative esophageal varices without tumor emboli in the portal trunk or primary portal branches.

Adult↗

Induction of cerebrospinal fluid eosinophilia in rats by the intraventricular injection of Angiostrongylus cantonensis antigen.

Resistance to Angiostrongylus cantonensis is contingent upon the generation of an eosinophilic response in the CSF of infected hosts. We have studied the parameters required for the generation of this CSF eosinophilia in normally permissive rats. We initially induced a marked peripheral eosinophilia in rats by infection with either Mesocestoides corti or Angiostrongylus cantonensis or the surgical transfer of A. cantonensis young adult worms (YA) into their pulmonary arteries. Next, we injected various antigens into the ventricles of these rats. A. cantonensis-preinfected rats demonstrated significant CSF eosinophilia following injection of A. cantonensis egg antigen, 1st-stage larval (L1) antigen, or M. corti antigen, but not following YA antigen inoculation. A. cantonensis egg and M. corti antigens were potent chemoattractants for eosinophils in an in vitro chemotaxis assay. These data indicate that peripheral eosinophilia, meningeal stimulation by A. cantonensis infection and the presence of potent chemoattractants, e.g., egg and L1 antigens are prerequisites for CSF eosinophil accumulation in permissive rat hosts.

Angiostrongylus cantonensis↗

Analysis of splenic and thymic lymphocyte subpopulations in chickens infected with Salmonella enteritidis.

Lymphocytes expressing CD3, CD4, CD8, pan lymphocyte, IgA, IgG and IgM cell surface antigens were assessed by in the spleen and thymus of chickens following infection with Salmonella enteritidis using flow cytometric analysis. At 6 days post primary infection and 2 days post secondary infection with S. enteritidis, the percentages of IgA+ and IgM+ lymphocytes in the spleen were significantly increased (P < 0.05). At 2 days post secondary infection with S. enteritidis, the percentage of CD4+ T lymphocyte in the spleen and CD8+ T lymphocyte percentage in the thymus were significantly increased (P < 0.05). These results indicate that S. enteritidis infection induces changes in the spleen and thymus that reflect the dynamics of the host protective immune response.

Animals↗

Synthesis and pharmacological properties of ureidomethylcarbamoylphenylketone derivatives. A new potent and subtype-selective nonpeptide CCK-B/gastrin receptor antagonist, S-0509.

A novel series of CCK-B/gastrin receptor antagonists-ureidomethylcarbamoylphenylketone derivatives-were designed, synthesized, and evaluated for activity. Structure-activity relationship studies revealed the importance of a carboxylic acid at substituent R2 and tert-butoxycarbonyl group at R1 in structure A. Compound 7a (S-0509) showed remarkable affinity for the CCK-B/gastrin receptor and a subtype selectivity profile in vitro. Administration (id) of 7a led to excellent inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats with an ED50 value of 0.014 mg/kg. Furthermore, 7a proved to have poor blood-brain permeability by its small effect on enhancement of morphine analgesia. Thus, S-0509 has an increase in selectivity for the peripheral effects of gastrin antagonism from the central effects of CCK-B antagonism.

Animals↗

Dissociation of bone formation markers in bone metastasis of prostate cancer.

To clarify the meaning and clinical value of bone formation markers in bone metastasis from prostate cancer, we investigated the bone formation markers carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BA1-p) and osteocalcin, so-called bone gla protein (BGP) in 43 prostate cancer patients with and 46 patients without overt bone metastasis. Patients with bone metastasis were evaluated repeatedly by bone scan at intervals of 3-6 months. The expression patterns of bone formation markers in patients with progression of bone metastasis became dissociated; BA1-p and PICP were elevated in patients with progression of bone metastasis but BGP was not. Instead, BGP showed slight elevation in patients with improvement and complete remission of bone metastasis. PICP, BA1-p and BGP are all bone formation markers, but each marker appears in a different phase of bone formation: PICP appears in proliferation phase, BA1-p appears in matrix maturation phase and BGP appears in late bone formation phase. Our findings that BGP was not elevated in progression of bone metastasis and that it increased slightly with improvement and complete remission of bone metastasis may imply that the bone formation that occurs in blastic bone metastasis is different from normal bone formation.

Aged↗

The cGMP pathway is not responsible for the blunted hypoxic vasoconstriction in rat lungs after altitude exposure.

To examine the contribution of the cyclic guanosine monophosphate (cGMP) pathway in changes in pulmonary vasoconstriction during the initial days of altitude exposure, we tested the effects of LY83583 (an inhibitor of guanylate cyclase activation) and those of N(G)-monomethyl-L-arginine (an inhibitor of nitric oxide synthesis) on airway hypoxia- (3% O2) and angiotensin II- (AII, 0.2 microg) induced vasoconstrictions in lungs from the rats exposed to either moderate altitude (MA, 570 torr) or high altitude (HA, 430 torr) At 2 days' exposure, hypoxic response was significantly blunted compared with the response in low-altitude (LA, 710 torr) lungs in an altitude-dependent manner. At 7 days' exposure, the response was recovered fully in MA lungs but partially in HA lungs. AII response was not significantly blunted at 2 days' exposure, but was significantly augmented in an altitude-dependent manner at 7 days' exposure. LY83583 (10 micromol L(-1)) potentiated both responses in LA lungs but did not significantly potentiate either response in any altitude-exposed lungs. N(G)-monomethyl-L-arginine (10 micromol L(-1)) potentiated both responses in LA lungs but did not significantly potentiate either response in HA lungs at 2 days' and 7 days' exposure. Thus the cGMP pathway is not responsible for either the change in hypoxic vasoconstriction or the change in AII vasoconstriction in rat lungs during the initial 7 days of altitude exposure.

Altitude↗

Characterization of GH3 cells overexpressing basic fibroblast growth factor (FGF-2).

Basic fibroblast growth factor (FGF-2) is not only a potent mitogen for various cells but also a multifunctional factor with angiogenic and chemotactic activity, and the capacity to induce the synthesis of various proteinases and to modulate endocrine function. To clarify the role played by FGF-2 in the progression of pituitary tumor, we fused rat FGF-2 cDNA to the promoter SR alpha, consisting of the early promoter of SV40 and HTLV(I)-LTR, and we cotransfected GH3 cells with pSV2-neo by an electroporation method. After selection by G418, we obtained 7 neomycin-resistant clones. Southern blot analysis of genomic DNA revealed the presence of transfected rat FGF-2 cDNA in 4 of the 7 clones. To measure FGF-2 molecules, we established a new immuno-fluorometric assay system, using 3 monoclonal antibodies against different portions of human FGF-2. This assay had a minimum sensitivity of 10 pg/ml and cross-reacted neither with acidic fibroblast growth factor (FGF-1) nor insulin-like growth factor 1 (IGF-1), even at a concentration of 100 ng/ml. Although FGF-2 was undetectable in the culture medium of any of the clones, the cell homogenate contained a significant amount of FGF-2 (7.2 ng/mg protein) in 1 of the 4 FGF-2-transfected clones (GH3FGF(+)), whereas FGF-2 was not detected (< 5.2 pg/mg protein) in the cell homogenates of either the parent GH3 cells or the control cells transfected with pSV2-neo alone (GH3FGF(-)), GH3FGF(+) grew as adherent cells and formed epithelial sheets with a growth rate similar to that of control cells. The amount of prolactin(PRL) released by TRH was greater in GH3FGF(+) than that in GH3 or GH3FGF(-). On the other hand, the sensitivity to SRIF was increased in GH3FGF(+) compared with that in other clones. The findings of these in vitro studies indicate that FGF-2, if it is expressed in pituitary tumor cells, plays little if any role in cell growth but may modulate certain cell functions such as responsiveness to hormones.

Adenoma↗

Glycosaminoglycans in crystal-surface binding substances and their role in calcium oxalate crystal growth.

OBJECTIVE: To clarify the role of glycosaminoglycans (GAGs) in crystal-surface binding substances (CSBS) on the growth of calcium oxalate crystals in urine. MATERIALS AND METHODS: Urine samples (24 h) were collected from healthy men (aged 25-42 years) and CSBS were obtained from the pooled urine samples. The CSBS were digested with heparitinase or proteinase and the inhibition of crystal growth assessed before and after enzyme digestion. Anion-exchange chromatography and high-performance liquid chromatography (HPLC) were used to determine the types of GAGs contained in the CSBS. RESULTS: The inhibitory activity of CSBS on crystal growth decreased with concentration when digested with heparitinase or proteinase. HPLC showed that CSBS contained a small amount of dermatan sulphate and abundant heparan sulphate, both of which inhibited crystal growth. CONCLUSION: Both heparan sulphate and dermatan sulphate may inhibit calcium oxalate crystallization, the former being the predominant GAG in CSBS.

Adult↗

Pharmacological studies on a new antihypertensive agent, S-2150, a benzothiazepine derivative: 3. Hypotensive and antimyocardial-stunning effects in dogs.

The hypotensive and antimyocardial-stunning effects of a new 1,5-benzothiazepine antihypertensive agent, S-2150, were investigated in dogs. S-2150 (30 mg/kg, p.o.) decreased the blood pressure in conscious renal hypertensive dogs. Although the maximal hypotensive effect of S-2150 was observed at 5-9 h after administration, the effect of diltiazem was seen at 2.0 h. Arrhythmia was not observed as a hypotensive effects of S-2150 but was markedly induced by diltiazem. In anesthetized open-chest dogs, S-2150 (20 micrograms/kg/min, i.v.) caused by hypotensive effect similar to that of diltiazem but decreased myocardial work (double product) by much less than did diltiazem. S-2150 more promptly improved the local myocardial stunning caused by occlusion of the left anterior descending coronary artery and its reperfusion. This effect did not accompany the energy-sparing action in ischemic/reperfused myocardium, which was different from the case of diltiazem. In isolated dog mesenteric arteries, S-2150 relaxed KCl and phenylephrine contracture. These results suggest that S-2150 is a favorable hypotensive agent for hypertensive patients with ischemic heart disease. Blockage of both Ca2+ channels and alpha 1-adrenoceptors by S-2150 seems to lead to cardiovascular effects different from those of diltiazem.

Adenosine Triphosphate↗

Traumatic aneurysm of the temporal artery: a report of five cases.

Five cases of traumatic aneurysm of the superficial temporal artery are reported. Four patients clearly stated that they had sustained traumatic injuries within 3 months prior to the appearance of the pulsating aneurysms; in the remaining case, more than two years had passed before the appearance of the nodule, and it was without pulsation. Color Doppler echography was very useful for observing the circulation in these aneurysms. Histologically, these cases were pseudoaneurysms composed of small vessels with internal elastic lamina and adjacent connective tissue proliferation, suggesting a break in the arterial wall.

Adolescent↗