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Biomedical subjects

S Obayashi

Publications and source records attributed to S Obayashi.

At least 19 recordsLinked to original sources
PubMed2006

Enhancement of antitumor activity of herpes simplex virus gamma(1)34.5-deficient mutant for oral squamous cell carcinoma cells by hexamethylene bisacetamide.

Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a gamma(1)34.5-deficient herpes simplex virus type 1 (HSV-1) R849 for human oral squamous cell carcinoma (SCC) cells. Hexamethylene bisacetamide increased the viral yield, especially at a low input multiplicity of infection (MOI), and the transcription of immediate early genes of HSV-1. Hexamethylene bisacetamide treatment promoted the cytopathic effect of R849 and increased the proportion of dead cells. Hexamethylene bisacetamide produced more apoptotic cells in R849-infected cells as compared with parental HSV-1(F)-infected cells. The growth of oral SCC xenografts in nude mice was markedly suppressed by treatment with R849 in combination with HMBA, and the survival of the co-treated animals was significantly prolonged as compared with that of animals treated with R849 only. Herpes simplex virus type 1 mRNA was expressed in tumors and trigeminal neurons, but not in brain, lung, liver, and kidney. These results indicate that HMBA enhances the antitumor activity of R849 through the expression of immediate early genes without increasing its toxicity. Hexamethylene bisacetamide can be used as an enhancing agent for oncolytic therapy with HSV-1 mutants.

Acetamides↗
PubMed2001

Effect of endogenous dopamine on extrastriatal [¹¹C]FLB 457 binding measured by PET.

Central dopaminergic systems are known to be implicated in the pathophysiology of schizophrenia and recent in vivo dopamine receptor imaging studies have focused on the measurement of extrastriatal dopamine receptor. However, there are only a limited number of ligands that can measure the low-density D2 receptor in extrastriatal regions and their sensitivity to endogenous dopamine in extrastriatal regions has not yet been fully examined. In this study, the effect of endogenous dopamine on the extrastriatal binding of [11C]FLB 457 was examined in the rhesus monkey after facilitation with 1 mg/kg of methamphetamine (MAP) and was compared with the effect on the striatal binding of [11C]raclopride. The indices of receptor binding were obtained by four methods using cerebellum as a reference region. The bindings of [11C]FLB 457 in the frontal cortex, temporal cortex, and thalamus were not significantly changed after MAP treatment, while the striatal binding of [11C]raclopride was decreased by more than 20%. These results suggest that [11C]FLB 457 is not sensitive to endogenous dopamine in the extrastriatal regions of rhesus monkeys, despite a sufficient dose of MAP to decrease the binding of [11C]raclopride in the striatum.

Animals↗
PubMed2001

Functional brain mapping of monkey tool use.

When using a tool, we can perceive a psychological association between the tool and the body parts-the tool is incorporated into our "body-image." During tool use, visual response properties of bimodal (tactile and visual) neurons in the intraparietal area of the monkey's cerebral cortex were modified to include the hand-held tool. Visual properties of the monkey intraparietal neurons may represent the body-image in the brain. We explored tool use-induced activation within the intraparietal area and elsewhere in alert monkey brain using positron emission tomography (PET). Tool use-related activities compared with the control condition (simple-stick manipulation) revealed a significant increase in cerebral blood flow in the corresponding intraparietal region, basal ganglia, presupplementary motor area, premotor cortex, and cerebellum. These tool use-specific areas may participate in maintaining and updating the body-image for the precise guidance of a hand-held rake onto a distant reward.

Animals↗
PubMed2001

Relationship between exploratory eye movements and clinical course in schizophrenic patients.

Exploratory eye movements are psychophysiological indicators of schizophrenia as well as smooth pursuit eye movements. To investigate whether these eye movements change in accordance with the clinical course of the condition in schizophrenia, exploratory eye movements (number of eye fixations, mean eye scanning length, responsive search score, evaluation of reproduced Fig. 1 and 2) of 28 schizophrenic patients were evaluated in repeat test design, conducted an average of 8 months apart. Subjects were first-medicated schizophrenics, half were outpatients and the remaining half were inpatients at the Neuropsychiatry ward of Tokyo Medical and Dental University Hospital. Exploratory eye movement patterns did not improve despite an improvement in clinical symptoms of schizophrenia. This result and those of previous studies of the exploratory eye movements of schizophrenic patients' families suggest that exploratory eye movements reflect a schizophrenic vulnerability marker. Furthermore, decreased mean eye scanning length (MESL) values were observed in subjects who showed unimproved symptoms, particularly negative symptoms over an extended period of time. The result suggests that a decrease in the MESL value may be the most sensitive indicator in the development of chronicity in schizophrenia.

Adolescent↗
PubMed2001

Self-images in the video monitor coded by monkey intraparietal neurons.

When playing a video game, or using a teleoperator system, we feel our self-image projected into the video monitor as a part of or an extension of ourselves. Here we show that such a self image is coded by bimodal (somatosensory and visual) neurons in the monkey intraparietal cortex, which have visual receptive fields (RFs) encompassing their somatosensory RFs. We earlier showed these neurons to code the schema of the hand which can be altered in accordance with psychological modification of the body image; that is, when the monkey used a rake as a tool to extend its reach, the visual RFs of these neurons elongated along the axis of the tool, as if the monkey's self image extended to the end of the tool. In the present experiment, we trained monkeys to recognize their image in a video monitor (despite the earlier general belief that monkeys are not capable of doing so), and demonstrated that the visual RF of these bimodal neurons was now projected onto the video screen so as to code the image of the hand as an extension of the self. Further, the coding of the imaged hand could intentionally be altered to match the image artificially modified in the monitor.

Action Potentials↗
PubMed2001

17 Beta-estradiol increases nitric oxide and prostaglandin I2 production by cultured human uterine arteries only in histologically normal specimens.

These experiments were designed to investigate whether 17beta-estradiol (E2) modulates the endothelial function of perimenopausal human uterine arteries. After the artery specimen was cultured in the presence or absence of E2 at a physiologic concentration of 200 pg/ml, changes in isometric tension and cyclic nucleotide production were determined. Degree of intimal hyperplasia was assessed histologically and expressed as intima-to-media ratio. Acetylcholine produced an endothelium-dependent relaxation in six specimens (group I) of 12, which was inhibited by NG-nitro-L-arginine or indomethacin. However, the agonist failed to produce a definite relaxation in the remaining 6 (group II). The endothelium-dependent relaxation was significantly augmented after incubating with E2 only in group I specimens. Cyclic nucleotide production was significantly increased after E2 incubation only in group I specimens, whereas it was inhibited by NG-nitro-L-arginine or indomethacin. Histologic study revealed that the six specimens of group I had normal intima (intima-to-media ratio = 19.1+/-1.8%) and the remaining six of group II had intimal hyperplasia (intima-to-media ratio = 53.6+/-5.3%). Increased production of cyclic nucleotides occurred in uterine arteries with normal intima but not in arteries with intimal hyperplasia derived from perimenopausal women.

Adult↗
PubMed2000

Subjective image of invisible hand coded by monkey intraparietal neurons.

Humans can perform purposeful hand actions even blindly in the dark, perhaps using mental images of the hand. To demonstrate such subjective body images, this study describes the activities of bimodal (somatosensory and visual) neurons in the monkey intraparietal cortex. Visual stimuli moving into the space encompassing their somatosensory receptive fields (s-RFs) on the hand activated these neurons, forming visual receptive fields (v-RFs) as if coding a hand-image. After the hand was hidden by covering it with an opaque plate, the v-RF persisted over the plate above the invisible s-RF. Furthermore, when the hand was moved invisibly under the plate, the v-RF moved over the plate to follow the invisible s-RF. Thus, monkeys can maintain and update subjective body images in the mind, and they are coded by intraparietal bimodal neurons.

Animals↗
PubMed1998

The activities of the Tokyo Center.

The main World Health Organization (WHO) activities of the Tokyo Center are as follows: (1) It performed the research project entitled 'A Bio-Psycho-Social Study on Children with Emotional and Behavioral Problems' in cooperation with the Beijing and Seoul Centers from 1985 to 1987. These results suggested that the deviant behavior of children in the general population had no biological background, but presumably stemmed from psychosocial disadvantages. (2) It has participated in a field trial for the proposed draft for chapter V of the ICD-10 as the Field Trial Coordinating Center in Japan since 1986 and the first Japanese edition of the ICD-10 Classification of Mental and Behavioral Disorders: Clinical Descriptions and Diagnostic Guidelines were published in 1993. (3) It proposed the collaborative project exploratory eye movements in patients with schizophrenia in 1989 and has promoted the project with the cooperation of six centers that included Beijing, Casablanca, Montreal, Munich, Prague and Sapporo. The findings of the present project indicated that exploratory eye movements may be specific to schizophrenia and can be practically used to discriminate schizophrenia without significantly depending on language.

Adolescent↗
PubMed1998

[When do strokes occur?--analysis of diurnal variation and activity during the onset].

The diurnal variation and activity during the onset of stroke were examined in more than 700 consecutive patients. 304 cases with hypertensive intracerebral hemorrhage (HIH), 214 cases with subarachnoid hemorrhage (SAH) and 201 cases with obstructive cerebrovascular disease (OCVD) were investigated about the time of onset. Concerning the activity during the onset, 296 cases with HIH, 215 cases with SAH and 198 cases with OCVD were examined. HIH occurred frequently between 1500-1800 hours, 0600-0900 hours and 1800-2100 hours. SAH occurred frequently between 0900-1200 hours, 1500-1800 hours and 1800-2100 hours. Both HIH and SAH were least likely to occur between 0000-0300 hours. OCVD exhibited a small peak incidence between 0900-1200 hours, but there were no differences between the groups for the other time periods. Both HIH and SAH were likely to occur frequently in the lavatory, while bathing and during meals. HIH also occurred frequently during physical work, while SAH occurred as frequently during mental work or housework as during hard physical labor. OCVD commonly occurred during sleep or relaxation. The relationship between diurnal variation in stroke and the circadian variation of blood pressure is discussed. The incidence of all three types of strokes during work was higher in the non-aged group (patients under 66 years) than in the aged group (patients over 66 years). HIH and SAH occurred associated with alcohol consumption more frequently in the non-aged group than in the aged group. It is likely that the difference of the time and of the activity during the onset between aged group and non-aged group reflects the difference of life-style between aged and non-aged people.

Activities of Daily Living↗
PubMed1997

Effect of nicotine on the intimal hyperplasia after endothelial removal of the rabbit carotid artery.

1. The present experiments were designed to investigate the effect of long-term oral nicotine (10 mg/200 ml/kg/day for 7 weeks) on the intimal hyperplasia after endothelial removal of the rabbit carotid artery. 2. The plasma concentrations of nicotine were determined to be 11.7-12.5 ng/ml during the term of administration and corresponded to the plasma levels in human smokers. 3. Six weeks after the endothelial removal, light microscopy revealed a marked intimal hyperplasia. Administration of nicotine tended to accelerate the intimal hyperplasia, which was estimated by comparing the histological findings, DNA content and wet weight of the vessel wall. 4. Acetylcholine- and A23187-induced endothelium-dependent relaxations were greatly impaired in the hyperplastic artery strips. The impairment of relaxations tended to be accelerated in the nicotine group. Sodium nitroprusside-induced relaxation was not different between the control and the hyperplastic artery strips and remained unaffected in the nicotine group. 5. The concentrations of endogenous nitric oxide (NO) synthesis inhibitors, NG-monomethyl-L-arginine (L-NMMA) and asymmetrical NG,NG-dimethyl-L-arginine (ADMA) were significantly more increased in the regenerated endothelial cells compared with those in the control endothelial cells. The concentrations of L-NMMA and ADMA in the regenerated endothelial cells were significantly increased by as much as 1.3 x 10(-6) and 5.6 x 10(-7) M, respectively, in the nicotine group. 6. Immunoreactive endothelin-1 was significantly increased in the hyperplastic vessel wall (2.4 times that of the control) in 6 weeks. Administration of nicotine tended to increase the level. 7. It seems possible to assume from these results that, although, under the present experimental conditions, nicotine exhibited a tendency to accelerate the intimal hyperplasia after endothelial removal, the longer exposure to nicotine or a higher dose of the agent or both would significantly accelerate the intimal hyperplasia through the enhanced impairment of endothelium-derived relaxing factor/ NO production, which might be brought about by the enhanced increases in L-NMMA and ADMA concentrations, and the enhanced increase in endothelin-1 in the vessel wall.

Animals↗
PubMed1997

The mechanism of myometrial contractions induced by endothelin-1 in rat.

Experiments were performed to characterize endothelin-1-induced contractions and the role of endothelin (ET) receptor subtypes in rat myometrium. The binding sites of [(125)I]-ET-1 were saturable with high affinity. Scatchard plot analysis revealed that ET-1 binding sites in the myometrium constituted a single population. The dissociation equilibrium constant (Kd) and the maximum binding sites (Bmax) were determined to be 48.9+/-3.0 pM and 1364.0+/-210.3 fmol/mg protein respectively. Specific [(125)I]-ET-1 binding was inhibited completely by unlabelled ET-1 and Ro 46-2005 (mixed-type ET receptor antagonist), but not fully (90.7+/-1.4%) by BQ 123 (a selective ETA receptor antagonist), and not at all by RES 701-1 (a selective ETB receptor antagonist). ET-1 induced myometrial contractions were composed of two types, an increase in resting tone and rhythmic contractions. These contractions were inhibited by BQ 123 and Ro 46-2005, but not by RES 701-1. ET-1-induced contractions were greatly reduced in Ca2+-free Krebs' solution. Nifedipine abolished the rhythmic contractions without affecting the increase in resting tone. These results suggest that ETA receptors are predominantly localized in rat myometrium and that excitation of ETA receptors evokes two types of contractions by increasing the cytoplasmic Ca2+ concentration.

Animals↗
PubMed1996

Intimal hyperplasia in human uterine arteries accompanied by impaired synergism between prostaglandin I2 and nitric oxide.

1. The present experiments were designed to investigate the mechanisms causing intimal hyperplasia in connection with the impaired synergism between prostaglandin I2 (PGI2) and nitric oxide (NO) in human uterine arteries (UAs). 2. In order to assess the magnitude of intimal hyperplasia, the intima:media ratio (%) was estimated with the aid of an image analyser. Human UAs were classified into two groups, I and II on the basis of the ratio and the degree of elastin deposition of histologically normal specimens. The intima:media ratio in group II was determined to be 38.9 +/- 7.7% (n = 6), which was significantly (P < 0.01) higher than that in group I (16.5 +/- 1.5%, n = 7). Less deposition of elastin was found in group I than in group II. 3. The relaxation activities of iloprost (IP) as a stable analogue of PGI2 and sodium nitroprusside (SNP) as a NO donor were not different between the two groups. When the minimum concentrations (Cmin) of IP and SNP in producing relaxation were applied together to the UA strips, these compounds interacted synergistically in group I. The observed relaxation (48.7 +/- 8.8%, n = 7) in this group was significantly (P < 0.01) greater than the predicted value of 18.8 +/- 3.1% (n = 7) (the mathematical sum of the relaxations caused by IP and SNP alone). By contrast, these agents interacted in an additive manner in group II. The observed relaxation (20.8 +/- 9.5%, n = 6) was not significantly different from the predicted value (18.6 +/- 2.4%, n = 6) in this group. 4. During the relaxation produced by the addition of IP and SNP alone or in combination, the changes in cyclic nucleotides (cyclic AMP and cyclic GMP) contents (pmol mg-1 protein) were assayed. When IP and SNP at Cmin were applied together to the UA strips, these compounds interacted synergistically in increasing cyclic nucleotides in group I. The observed net increase in the content was determined to be 1.46 +/- 0.30 (P < 0.05 vs. the predicted value of 0.67 +/- 0.12) in this group (n = 7). By contrast, the observed net increase (0.40 +/- 0.07, n = 6) did not exceed the predicted value (0.65 +/- 0.07, n = 6) in group II. 5. These results suggest that the formation of intimal hyperplasia in group II may be closely related to the impaired synergism between PGI2 and NO in the human UAs.

Adult↗
PubMed1995

Different localization of ETA and ETB receptors in the hyperplastic vascular wall.

We investigated which subtypes of endothelin-1 (ET-1) receptors are involved in the pathogenesis of angioplasty-induced lesion formation in the rabbit carotid artery. Four weeks after removing endothelial cells (EC), we noted a marked intimal hyperplasia. The Bmax values for [125I]ET-1 and [125I]IRL1620 (an agonist for the ETB receptors) bindings were greater in the hyperplastic artery, without changes in Kd values. [125I]ET-1 binding was completely inhibited by unlabeled ET-1 and Ro 46-2005, a mixed-type antagonist for the ETA and ETB receptors, but partially by BQ123, a selective antagonist for ETA receptors, and IRL1620. The [125I]ET-1 binding sites not inhibited with BQ123 were significantly increased in the hyperplastic artery. The binding study suggested the presence of non-ETA/non-ETB receptors. The rank order of the increasing ratio in the density of receptors was ETB > putative non-ETA/non-ETB > total ET-1 receptors > ETA. The histochemical experiments with biotinylated ET-1 at lysine-9 side chain alone or in combination with unlabeled ET-1, BQ123, Ro 46-2005, or IRL1620, showed the ETA receptors to be localized mainly in the media, whereas the ETB receptors localized mainly in the neointima. These results suggest that the increased ET-1 receptors, especially ETB and/or putative non-ETA/non-ETB, are closely related to the occurrence of the intimal hyperplasia after endothelial removal.

Analysis of Variance↗
PubMed1995

Role of endothelium in the human uterine arteries during normal menstrual cycle.

1. The present experiments were designed to investigate the role of endothelium in the human uterine arteries during the normal menstrual cycle. 2. Acetylcholine (ACh) produced a concentration-dependent relaxation response during the higher level of plasma 17 beta-oestradiol (E2) (follicular and luteal phases, E2 = 131.9 +/- 15.9 pg ml-1, n = 13; group I). However, the agent did not produce a definite relaxation, but produced a slight contraction during the ovulatory and menstruation phases (E2 = 19.8 +/- 2.9 pg mg-1, n = 5; group II). During the follicular and luteal phases (E2 = 181.1 +/- 9.0 pg ml-1, n = 6), ACh produced a slight contraction, but not relaxation in 6 cases (group III). Relaxation in response to A23187 in group II was not different from that in group I, while it was significantly (P < 0.05 and P < 0.005) reduced in group III. Sodium nitroprusside (SNP)-induced relaxation was similar in the three groups. 3. Correlation between the maximum response to ACh and the plasma E2 was highly significant (gamma = 0.8142, P < 0.001) in 18 cases of groups I and II, but not in all 24 cases including group III (gamma = 0.1183, NS). 4. Relaxations in response to ACh in group I or A23187 in all groups were abolished after removal of the endothelium. In group I, ACh- and A23187-induced relaxations were greatly inhibited by methylene blue or NG-nitro-L-arginine (L-NOARG) and partially inhibited by indomethacin. None of these treatments except for methylene blue modified the SNP-induced relaxation, which was significantly inhibited by methylene blue.5. The A23187-induced relaxation was hardly affected by methylene blue or L-NOARG in group III,but was partially inhibited by these agents in group II. The effect of indomethacin in inhibiting the A23187 induced-relaxation was most potent (58.9%) in group III and least (16.9%) in group I.6. There were no histological changes in 14 cases out of 18 (groups I and II), but very slight intimal thickening was observed in 4 cases in group I. On the other hand, severe intimal thickening was observed in all 6 cases in group III.7. These results indicate that, in human uterine artery strips, ACh and A23187 cause endothelium dependent relaxations, which are mediated mainly through EDRF/NO in group I, mainly prostacyclin(PGI2) in group III, or both in group II. It is suggested that lack of the production/release of EDRF/NO and/or of interaction between EDRF/NO and PGI2 might play a role in the formation of intimal thickening in human uterine arteries.

Acetylcholine↗
PubMed1995

Accumulation of endogenous inhibitors for nitric oxide synthesis and decreased content of L-arginine in regenerated endothelial cells.

1. We examined regeneration of endothelial cells (ECs), neointima formation, decreased endothelium-dependent relaxation (EDR) and changes in the contents of L-arginine, NG-monomethyl-L-arginine (L-NMMA), asymmetrical NG, NG-dimethylarginine (ADMA) and symmetrical NG,NG-dimethylarginine (SDMA) in the regenerated ECs, 6 weeks after balloon denudation of the rabbit carotid artery. 2. Regeneration of ECs was completed in 6 weeks and a significant neointima formation accompanied by the decreased EDR was observed. 3. L-NMMA and ADMA contents in the regenerated ECs (23.5 +/- 4.3 and 21.2 +/- 2.0 pmol mg-1 DNA, respectively) were significantly (P < 0.05 and P < 0.01) higher than those in the control ECs (8.8 +/- 3.0 and 7.4 +/- 1.9 pmol mg-1 DNA, respectively), whereas L-arginine was significantly (P < 0.005) decreased in the regenerated ECs (31,470 +/- 1,050 pmol mg-1 DNA) as compared to that in the control ECs (47,870 +/- 1,890 pmol mg-1 DNA). SDMA content was below the assay limits. 4. L-NMMA and ADMA, but not SDMA, inhibited the EDR induced by acetylcholine in a concentration-dependent manner. The inhibition with L-NMMA and ADMA was prevented by an addition of L-arginine, but not by D-arginine. 5. These results suggest that the accumulation of endogenous inhibitors for nitric oxide synthesis and decreased L-arginine content are associated with decreased NO production/release from regenerated ECs and neointima formation.

Acetylcholine↗
PubMed1992

[Study of recombinant human erythropoietin treatment on the anemia of predialysis patients].

We conducted a multiple-center joint study on the effects of recombinant human erythropoietin (rEPO) for predialysis patients. rEPO was intravenously administered to 42 predialysis patients (13 males and 29 females) with hematocrit (Ht) levels of less than 30%. The subjects were divided into group A (28 cases) in which rEPO was administered twice a week, and group B (14 cases) with rEPO administration once a week. The initial administration dosage was 6000IU/week. The Ht levels were 22.6 +/- 3.3% for group A and 23.2 +/- 2.7% for group B before the administration of rEPO, and increased to 31.0 +/- 4.0% and 27.7 +/- 3.7% respectively twelve weeks after initiating administration. The levels of effective improvement on anemia included 'markedly effective' in 17 cases (80.9%) and 'effective' in 2 cases (9.5%) in group A, and 'markedly effective' in 5 cases (41.7%) and 'effective' in 3 cases (25.0%) in group B. No significant change was seen in serum creatinine (Cr) levels during the study period. In the evaluation of renal function by reciprocal serum creatinine (1/Cr), a consistent tendency was not recognized; thus, suggesting that the rEPO administration had no effect on the renal function. No variation of blood pressure was seen. As far as side effects were concerned, headache and heavy headedness were recognized in four cases. There were, however, no cases in which the severity of the side effects dictated the discontinuation of the rEPO administration. In conclusion, rEPO was judged to be a safe and effective treatment for the anemia of predialysis patients.

Adult↗