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Biomedical subjects

K Koga

Publications and source records attributed to K Koga.

At least 73 records · Page 4Linked to original sources

Correlation between magnetic resonance images and draining patterns in dural arteriovenous fistulas with leptomeningeal venous drainage.

OBJECTIVE: To compare abnormal intensity areas on intracranial magnetic resonance images (MRI) and the pattern of venous drainage in dural arteriovenous fistulas (DAVFs) with retrograde venous drainage. METHODS: Thirteen patients with retrograde venous drainage of DAVFs were divided into two groups based on the venous drainage pattern determined by detailed angiographic and MRI study. In group 1 there was an accessory route draining into another sinus besides the main draining sinus. In group 2 no such accessory route was present. RESULTS: In group 1 patients (n = 8), MRI detected no unusual intensity areas; 5 patients in this group had episodes of bleeding. Angiographically, in this group retrograde venous drainage tended to occur via multiple varices. On the other hand, none of the 5 group 2 patients experienced a bleeding episode. Angiographically, there was a low incidence of varices. On T2-weighted images, these patients had a hyperintensity area. Following treatment, these areas of abnormality disappeared on T2-weighted MRI. CONCLUSION: Among 13 patients with DAVFs which drained retrogradely, those with a variceal accessory route (Group 1, n = 8) had a higher incidence of haemorrhage. In patients without such an accessory route (Group 2, n = 5) abnormal signal intensity on MRI was indicative of venous congestion. Continuous-mode angiography and MRI study were useful in the precise identification of DAVFs with a venous drainage route.

Aged↗

Systemic administration of adenosine A(2A) receptor antagonist reverses increased GABA release in the globus pallidus of unilateral 6-hydroxydopamine-lesioned rats: a microdialysis study.

The ability of adenosine A(2A) receptor antagonists to exhibit antiparkinsonian activity has recently been reported, but the mechanisms of action are still unknown. Since A(2A) receptors have been localized to GABAergic striatopallidal neurons, it is probable that these antagonists affect the activity of these neurons. In the present study, extracellular GABA basal levels were increased in the ipsilateral striatum and globus pallidus following a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. The A(2A) receptor-selective antagonist KW-6002 (3mg/kg, p.o.) caused a marked and sustained decrease of extracellular GABA levels in the globus pallidus of the 6-hydroxydopamine-lesioned rats, whereas no changes in GABA levels were observed in the globus pallidus of the non-lesioned rats. Microinjection of the A(2A) receptor agonist CGS21680 (0.005-0.5 microg) into the striatum of non-lesioned animals increased GABA concentrations in the globus pallidus, which was abolished by the voltage-dependent Na(+) channel blocker tetrodotoxin (1 micromol/l) delivered locally to the globus pallidus via the dialysis membrane. Furthermore, intrapallidal infusion of CGS21680 (10 micromol/l) also increased GABA levels in the globus pallidus. These data indicate that GABA release from striatopallidal neurons is regulated through A(2A) receptors in both the striatum and globus pallidus. The reversal of the 6-hydroxydopamine-induced increase in pallidal GABA levels by KW-6002 suggests that the antiparkinsonian effects of A(2A) receptor antagonists occur on the striatopallidal neurons.

Adenosine↗

Venodilatory effect of pranidipine, a calcium channel blocker, monitored with perfluorocarbon in vivo (19)F-NMR spectroscopy.

We previously reported that the (19)F-NMR signal intensity of perfluorocarbon was increased by a venodilator, nitroglycerine, and decreased by an arteriodilator, hydralazine. In the present study, we demonstrated that pranidipine, a calcium channel blocker, increased the intensity of the FC-43 signal, while nifedipine, a prototype of calcium channel blockers, did not. These results suggest that pranidipine dilates the venous system in contrast to nifedipine.

Animals↗

Modification of ceftibuten transport by the addition of non-ionic surfactants.

The effects of non-ionic surfactants on the carrier-mediated transport of ceftibuten by rat intestinal brush-border membrane vesicles (BBMVs) were investigated. Ceftibuten uptake by BBMVs was measured by a rapid filtration technique. The concentration of surfactants for the uptake experiments was determined by a decrease in the turbidity of BBMV suspension and by the release of an impermeable probe, 2',7'-bis(carboxyethyl)-4(5)-carboxyfluorescein, from the vesicle inside. In fact, the surfactant concentration of 0. 03% (w/v) was selected to maintain the stability of BBMVs. The extent of ceftibuten uptake by BBMVs with various surfactants was correlated with their physicochemical properties, i.e. hydrophile-lipophile balance (HLB), critical micelle concentration (c.m.c.), average diameter of micelle colloid, and polydispersity determined by particle size distribution. The surfactants used were divided into two groups on the basis of polydispersity index (d(w)/d(n)), i.e. low polydispersity (d(w)/d(n) congruent with1) and high polydispersity d(w)/d(n)2). The ceftibuten uptake due to the addition of surfactants with low polydispersity increased with a decrease in the HLB number. These results indicate that the ceftibuten transport is modulated by the size distribution and hydrophobicity of surfactants. In addition, the effects of surfactants on the membrane lipid fluidity monitored by diphenylhexatriene (DPH) and trimethylammonium diphenylhexatriene (TMA-DPH) were investigated. There was significant correlation between ceftibuten uptake and the fluorescence anisotropy of TMA-DPH-labeled membranes due to the addition of surfactants with low polydispersity (r=-0.81, P<0.0001). These results suggest that surfactants with low polydispersity, in part, increase or decrease the outer membrane leaflet, thereby enhancing or suppressing the ceftibuten transport by BBMVs, and that ceftibuten transport caused by surfactants with low polydispersity may be strongly dependent on the hydrophobic interaction.

Animals↗

Isolation of replicational cue elements from a library of bent DNAs of Aspergillus oryzae.

Two fragments that could function as replicational cue elements were isolated from a genomic DNA digest of Aspergillus oryzae on the basis of abnormal behavior in polyacrylamide gel electrophoresis. The vector used in this study contained a scaffold-associated region of the Drosophila melanogaster ftz gene to provide nuclear retention. Neither fragment contained a yeast ARS consensus sequence or an eukaryotic topoisomerase II binding sequence. One of the fragments showed sequence homology with the mitochondrial replication origin of Candida utilis and a portion of mitochondrial DNA of Aspergillus nidulans. This plasmid carrying the cue fragment could also replicate in HeLa and NIH3T3 cells.

Animals↗

Synergistic induction of pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression by nerve growth factor and PACAP in PC12 cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression was analyzed in PC12 cells. PC12 cells transfected with a PACAP promoter-luciferase reporter construct were utilized to investigate the effects of PACAP, either alone or in combination with nerve growth factor (NGF), on PACAP transcriptional response. PACAP induced transcription from the PACAP promoter through PACAP type I receptor (PAC1 receptor). PACAP gene transcription was also induced by NGF. Simultaneous treatment with PACAP and NGF resulted in a synergistic transcriptional response that was more than three times the predicted response, based on a simple additive effect of both agents. This synergism in transcriptional response paralleled the PACAP mRNA levels, as determined by RT-PCR and northern blotting. The level of PACAP mRNA peaked 3 h after stimulation and gradually returned to basal levels by 48 h. PC12 cells are known to express predominantly the hop isoform of the PAC1 receptor, which positively couples to both adenylate cyclase and phospholipase C. To determine the role of the cyclic AMP and protein kinase C pathways in PACAP gene expression, the effects of forskolin and phorbol 12-myristate 13-acetate (PMA) were then examined. PMA did not alter PACAP mRNA levels but enhanced forskolin-induced PACAP mRNA expression. Down-regulation of protein kinase C blocked the ability of PACAP to stimulate PACAP mRNA expression. The mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) inhibitor PD98059 also blocked the PACAP mRNA expression induced by either PACAP or NGF but not that induced by a combination of PACAP and NGF. These results suggest that PACAP stimulates the PACAP gene expression in PC12 cells at least in part through activation of adenylate cyclase and protein kinase C signaling pathways and that the ERK1/2 cascade is involved in PACAP and NGF-induced PACAP gene expression, although redundant signaling pathways may also be involved. The present finding showing that PACAP in combination with NGF causes a synergistic increase in PACAP gene expression in PC12 cells supports the idea that PACAP acts as an autocrine regulatory factor.

Animals↗

Magnetic resonance arthrography of the temporomandibular joint.

PURPOSE: This study evaluated the usefulness of magnetic resonance arthrography (MRAr) in imaging the pathologic temporomandibular joint (TMJ). PATIENTS AND METHODS: Thirteen TMJs of 11 patients with chronic TMJ pain and disability were examined with MRAr. T1-weighted and T2-weighted first spin-echo sequence with fat suppression images were obtained after the intra-articular injection of gadopentetate dimeglumine. RESULTS: The disc, the posterior attachment, and the presence of perforations and adhesions were evaluated in each image. All of these anatomic and pathologic structures were clearly detected. CONCLUSION: MRAr appears to be a promising imaging modality in detecting adhesions and perforations in the TMJ. The MRAr findings simplified the decision of whether a patient should undergo surgery.

Adult↗

Increased concentrations of soluble tumour necrosis factor receptor (sTNFR) I and II in peritoneal fluid from women with endometriosis.

Tumour necrosis factor alpha (TNFalpha), a proapoptotic cytokine, is known to be present in peritoneal fluid from women with endometriosis. An emerging view is that soluble TNF receptors (sTNFR) can modulate the effects of TNFalpha by acting as TNFalpha antagonists. To assess the relevance of sTNFRs in the pathophysiology of endometriosis, concentrations of sTNFR I, sTNFR II and TNFalpha in peritoneal fluid from women with endometriosis (n = 53) and without endometriosis (n = 40) were measured. Concentrations of both sTNFR I and sTNFR II in peritoneal fluid from women with endometriosis were significantly higher than in peritoneal fluid from women without endometriosis, both in the follicular and the luteal phases. TNFalpha concentrations did not differ in patients with and without endometriosis in both phases. When stratified by the stage of the disease, women with both stages I/II and stages III/IV exhibited significantly higher concentrations of sTNFR I and sTNFR II in peritoneal fluid, compared with women without endometriosis, whereas no appreciable difference in the concentrations was detected between stages I/II and stages III/IV. A significant correlation was found between the concentrations of sTNFR I and sTNFR II; while the correlations between TNFalpha and sTNFR I or sTNFR II, were either not significant or were very weak. Furthermore, mRNA for the membrane-associated TNF receptor type 1 and TNF receptor type 2, both of which convey the effects of TNFalpha, were shown to be expressed in endometriotic tissues as well as eutopic endometrium. Together, these findings suggest a possible involvement of sTNFRs in the pathophysiology of endometriosis.

Adult↗

Stem cell factor (SCF) concentrations in peritoneal fluid of women with or without endometriosis.

PROBLEM: In the quest for possible involvement of stem cell factor (SCF), a cytokine known to have multiple effects, in the pathogenesis of endometriosis, we evaluated concentrations of SCF in peritoneal fluid (PF) of women with or without endometriosis. METHOD OF STUDY: SCF concentrations in PF collected from women undergoing laparoscopy were measured, using a specific enzyme-linked immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction (RT-PCR) analysis to detect gene expression of c-kit, the receptor for SCF, was performed using the endometriotic tissue and the eutopic endometrium collected during the operation. RESULTS: SCF concentrations in PF of women with endometriosis were significantly higher compared to women without endometriosis. Looking at SCF concentrations in PF of women with endometriosis stratified by disease stage, women with stage I and II exhibited relatively higher SCF levels in PF, whereas SCF levels in PF with stage III and IV were comparable with those without endometriosis. The expression of mRNA for c-kit was detected in both the endometriotic tissue and the eutopic endometrium. CONCLUSION: We demonstrated an elevation in SCF levels in PF associated with endometriosis and the presence of its receptor in endometriotic tissues. Given the known pleiotropic properties of SCF, the present results suggest that SCF might play a role in the pathogenesis of endometriosis.

Adult↗

Evidence for the presence of angiogenin in human follicular fluid and the up-regulation of its production by human chorionic gonadotropin and hypoxia.

Angiogenesis is an essential event during the development of the ovarian follicle and ensuing formation of the corpus luteum. We investigated the presence of angiogenin, a potent inducer of angiogenesis, and the regulatory mechanisms of its production in the human ovary. Follicular fluid (FF) and granulosa cells (GCs) were collected from women undergoing in vitro fertilization and embryo transfer. The presence of angiogenin in FF and GCs was demonstrated by Western blot analysis. The production of angiogenin by cultured GCs was stimulated with the addition of human CG or cAMP or under the hypoxic milieu. Concentrations of angiogenin in FF from an individual follicle were positively correlated with those of progesterone, but not estradiol and testosterone. Given the presence of angiogenin in FF and up-regulation of its production by human CG and hypoxia, it seems logical to assume that angiogenin may play a role as a local angiogenic factor in the human ovary.

Adult↗

Rate enhancement with high ratio of the monoalkylated product to the dialkylated product in the alkylation of the lithium enolate of 1-tetralone with reactive alkyl halides.

The reactions of the lithium enolate of 1-tetralone with reactive alkyl halides were examined in the absence and in the presence of 3 eq of various ligands for the lithium. It is shown that the rates of the reactions are enhanced greatly in the presence a tetradentate amine (1,1,4,7,10,10-hexamethyltriethylenetetramine), and the ratio of the monoalkylated product to the dialkylated product is increased under shorter reaction times.

Alkylation↗

Podophyllotoxin aza-analogue, a novel DNA topoisomerase II inhibitor.

The pendant E-ring moiety of the podophyllotoxin aza-analogue 1 that is a potent inhibitor of microtubule assembly was modified in order to acquire inhibitory activity of DNA topoisomerase II. The monophenolic analogue 2 did not exhibit human topoisomerase II inhibition, while the ortho-quinone 3 that was obtained by oxidation of 2 inhibited its catalytic activity (decatenation) in a dose-dependent manner and stimulated double strand DNA breaks in supercoiled circular plasmid DNA, resulting in the production of linear DNA. These results showed that the topoisomerase II inhibition of the ortho-quinone 3 is due to stabilization of the topoisomerase II-DNA covalent binary complex. On the other hand, the ortho-quinone 3 did not inhibit the relaxation process of supercoiled DNA by topoisomerase I at concentrations up to 400 microM, nor was intercalation observed in unwinding measurements of 3. Therefore, the ortho-quinone 3 was shown to be a novel nonintercalative topoisomerase II specific inhibitor that stabilizes the cleavable complex. The present results suggest that the 4'-free hydroxyl group on the E-ring and the sugar moiety on the C-ring are not a prerequisite for topoisomerase II inhibition by podophyllotoxin derivatives.

DNA↗

Stereoselective reactions. XXXII. Enantioselective deprotonation of 4-tert-butylcyclohexanone by fluorine-containing chiral lithium amides derived from 1-phenylethylamine and 1-(1-naphthyl)ethylamine.

Enantioselective deprotonation of 4-tert-butylcyclohexanone was examined using 1-phenylethylamine- and 1-(1-naphthyl)ethylamine-derived chiral lithium amides having an alkyl or a fluoroalkyl substituent at the amide nitrogen. The lithium amides having a 2,2,2-trifluoroethyl group on the amide nitrogen are easily accessible in both enantiomeric forms, and were found to induce good enantioselectivity in the present reaction.

Amides↗

Energy preserving effect of l-cis diltiazem in isolated ischemic and reperfused guinea pig hearts: a 31P-NMR study.

We determined the effect of 1-cis diltiazem, the enantiomer of diltiazem (d-cis isoform), on the energy metabolism of isolated guinea pig hearts during ischemia-reperfusion. We used 31P-NMR to measure the high-energy phosphate content and intracellular pH (pHi) during global ischemia for 30 min followed by reperfusion for 30 min. Before ischemia, the left ventricular developed pressure (LVDP) was reduced less by 10 microM l-cis diltiazem than by 3 microM diltiazem or 500 nM nifedipine. However, 10 microM l-cis diltiazem preserved the intracellular ATP content during ischemia and reperfusion, reduced the end-diastolic pressure increase during ischemia and reperfusion, and restored LVDP after reperfusion. Nifedipine at 50 nM, which reduced the LVDP more than 10 microM l-cis diltiazem, showed no cardioprotective effect. Ten micromolar l-cis diltiazem and 3 microM diltiazem, but neither 50 nor 500 nM nifedipine, reduced the pHi decrease that occurred 25 or 30 min after the onset of ischemia. Therefore, l-cis diltiazem has a cardioprotective effect on ischemic and reperfused myocardium and is less cardiodepressive than diltiazem and nifedipine. The effect of l-cis diltiazem during ischemia and reperfusion involves energy preservation, which is probably independent of its Ca2+-channel blocking action.

Adenosine Triphosphate↗

Effects of acute and chronic administration of MCI-225, a new selective noradrenaline reuptake inhibitor with 5-HT3 receptor blocking action, on extracellular noradrenaline levels in the hypothalamus of stressed rats.

In the present study, we investigated the effects of acute and chronic systemic administration of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride), a newly-developed selective noradrenaline (NA) reuptake inhibitor with 5-HT3-receptor-blocking action, on extracellular NA levels in the hypothalamus of stressed and non-stressed rats by utilizing intracerebral microdialysis. Acute administration of MCI-225 (3 and 10 mg/kg, p.o.) significantly and dose-dependently increased extracellular NA levels in the hypothalamus in non-stressed rats. Footshock for 20 min also significantly increased NA levels in the hypothalamus of both groups of rats pretreated with vehicle and MCI-225. Although chronic administration of MCI-225 (3 or 10 mg/kg, p.o. for 14 days) did not alter the basal extracellular NA levels in the hypothalamus, the stress-induced increases in extracellular NA levels were significantly lower in rats chronically treated with MCI-225 (10 mg/kg) than those of rats pretreated with vehicle for the same period. The increase in extracellular NA levels induced by MCI-225 challenge (3 or 10 mg/kg, p.o.) were not different between rats chronically treated with MCI-225 or vehicle. These results suggest that MCI-225 enhances extracellular NA levels in the hypothalamus in both non-stressed and stressed rats by inhibiting NA uptake and that chronic systemic administration of MCI-225 did not alter basal extracellular NA levels, but reduced the increase in NA release caused by footshock stress. These data suggest the possibility that MCI-225 might possess anxiolytic and/or antidepressant properties.

Adrenergic Uptake Inhibitors↗

Expression of prophenoloxidase mRNA during silkworm hemocyte development.

Two clones encoding different prophenoloxidase isoforms were amplified by polymerase chain reaction of RNA from the hemocytes of an experimental strain of Bombyx mori. The nucleotide sequences of the clones and the deduced amino acid sequences were confirmed to be nearly identical to those of the orthologous clones previously obtained from a commercial race of B. mori. Northern blot hybridization using these clones as probes demonstrated that the prophenoloxidase mRNA in the hemocytes is expressed in a stage-specific manner during the final larval instar and pupal stage, showing a peak one day before pupation in males and on the day of pupation in females. A sexual difference was also observed when the content of prophenoloxidase protein in the hemolymph (including hemocytes) was measured by an enzyme-linked immunosorbent assay.

Amino Acid Sequence↗

Culture in vector-averaged gravity under clinostat rotation results in apoptosis of osteoblastic ROS 17/2.8 cells.

Space flight experiments and studies carried out in altered gravity environments have revealed that exposure to altered gravity conditions results in (mal)adaptation of cellular function. In the present study, we used a clinostat to generate a vector-averaged gravity environment. We then evaluated the responses of osteoblast-like ROS 17/2.8 cells subsequent to rotation at 50 revolutions per minute (rpm) for 6-24 h. We found that the cells started to detach from the substrate between 12 h and 24 h of rotation in clinostat but not in stationary cultures or after horizontal rotation (the latter serving as a motion control for turbulence, shear forces, and vibrations). At 24 h, 35% of clinorotated cells had detached and the cells underwent apoptotic death as evidenced by DNA fragmentation analysis, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining, and flow cytometry with Annexin V staining. The apoptotic death was associated with perinuclear distribution of cell-surface integrin beta1 and disorganization of actin cytoskeleton. These results suggest that vector-averaged gravity causes apoptosis of osteoblasts by altering the organization of the cytoskeleton. We hypothesize that apoptotic death of osteoblasts might play an important role in the pathogenesis of osteoporotic bone loss as observed in actual space flights.

Actins↗