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Biomedical subjects

H Matsuda

Publications and source records attributed to H Matsuda.

At least 253 records · Page 14Linked to original sources

Single-photon emission computed tomography of the brain in autism: effect of the developmental level.

Brain single-photon emission computed tomography was performed in 22 autistic and 10 nonautistic disabled patients. The regional cerebral blood flow in both laterotemporal and dorso-medio-lateral frontal areas decreased significantly in the autistic group compared with in nonautistic group. In the autistic group, the regional cerebral blood flow was significantly higher in the right temporal and right parietal lobes than that in the left ones. Inversely, the regional cerebral blood flow in the frontal and occipital lobes was significantly higher on the left side than on the right side. In the nonautistic group, except for in the dorso-medio-lateral frontal lobes (left > right), there was no difference in the regional cerebral blood flow in either cerebrum or cerebellum. A positive correlationship between regional cerebral flow and development quotient (intelligence quotient) was observed in the left laterotemporal and both dorso-medio-lateral frontal areas, and a negative one was observed in the cerebellar vermis area. These results suggest that the regional cerebral blood flow decrease in the temporal and frontal areas relates to not only the brain mechanism of autism reported previously but also intelligence levels.

Adolescent↗

Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration.

Prolonged or high-intensity exposure to visible light leads to photoreceptor cell death. In this study, we demonstrate a novel pathway of light-induced photoreceptor apoptosis involving the low-affinity neurotrophin receptor p75 (p75NTR). Retinal degeneration upregulated both p75NTR and the high-affinity neurotrophin receptor TrkC in different parts of Müller glial cells. Exogenous neurotrophin-3 (NT-3) increased, but nerve growth factor (NGF) decreased basic fibroblast growth factor (bFGF) production in Müller cells, which can directly rescue photoreceptor apoptosis. Blockade of p75NTR prevented bFGF reduction and resulted in both structural and functional photoreceptor survival in vivo. Furthermore, the absence of p75NTR significantly prevented light-induced photoreceptor apoptosis. These observations implicate glial cells in the determination of neural cell survival, and suggest functional glial-neuronal cell interactions as new therapeutic targets for neurodegeneration.

Animals↗

Alcohol absorption inhibitors from bay leaf (Laurus nobilis): structure-requirements of sesquiterpenes for the activity.

Through a bioassay-guided separation using inhibitory activity on blood ethanol elevation in oral ethanol-loaded rat, various sesquiterpenes having an alpha-methylene-gamma-butyrolactone moiety, costunolide (1), dehydrocostus lactone (2), zaluzanin D (3), reynosin (4), santamarine (5), 3alpha-acetoxyeudesma-1,4(15),11(13)-trien-12,6alpha-+ ++olide (6) and 3-oxoeudesma-1,4,11(13)-trien-12,6alpha-olide (7), were isolated as the active principle from the leaves of Laurus nobilis (bay leaf, laurel). In order to characterize the structure requirement for the activity, several reduction products (2a-2d) and amino acid adducts (2e, 2f) of the alpha-methylene-gamma-butyrolactone moiety were synthesized from 2 and the inhibitory activities of these sesquiterpenes, together with alpha-methylene-gamma-butyrolactone (12) and its related compounds (13-16), were examined. These results indicated that the gamma-butyrolactone or gamma-butyrolactol moiety having alpha-methylene or alpha-methyl group was essential for the inhibitory activity on ethanol absorption. Since 1, 2 and 12 showed no significant effect on glucose absorption, these sesquiterpenes appeared to selectively inhibit ethanol absorption. In addition, the acute toxicities of 1 and 2 in a single oral administration were found to be lower than that of 12.

4-Butyrolactone↗

Role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

OBJECTIVES: Nitric oxide is the most potent vasodilator among inflammation-mediated vasoactive substances. Tepid cardiopulmonary bypass has been known to maintain low vascular resistance and nitric oxide may also be involved. There has been no previous clinical study elucidating a role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass. METHODS: Thirty-one patients who underwent valvular surgery were randomly divided into two comparable groups; consisting of the hypothermic cardiopulmonary bypass (28 degrees C:14 patients) and the tepid cardiopulmonary bypass group (34 degrees C:17 patients). The serum levels of nitric oxide (NO(2)(-)+NO(3)(-)), prostaglandin E(2), bradykinin, 6-keto PGF1alpha, thromboxane B(2), endothelin-1, systemic vascular resistance index were measured before, 0, 12 and 24 h after cardiopulmonary bypass. RESULTS: The pattern of change in systemic vascular resistance index and nitric oxide during and after cardiopulmonary bypass were significantly different between the two groups (P=0.0008, P=0.02). The tepid group showed significantly lower levels of systemic vascular resistance index after cardiopulmonary bypass than the hypothermic group (0 h: 2278+/-735 vs. 4387+/-1289, 12 h: 1827+/-817 vs. 2817+/-1146 and 24 h: 1690+/-548 vs. 2761+/-641 dyne s cm(-5) m(2), P=0.0001, P=0.03, P=0. 0006). The nitric oxide levels were significantly higher at 0, 12 and 24 h after cardiopulmonary bypass in the tepid group than those in the hypothermic group (84.7+/-33.3 vs. 46.3+/-18.1, 69.8+/-31.1 vs. 40.1+/-17.5 and 80.1+/-38.5 vs. 39.1+/-15.6 micromol/l, P=0.008, P=0.03, P=0.01). The prostaglandin E(2) levels in the tepid group was significantly higher just after cardiopulmonary bypass than that in the hypothermic group (37.3+/-20.0 vs. 15.8+/-8.6 pg/ml, P=0.02). The bradykinin level in the hypothermic group was significantly higher just after cardiopulmonary bypass than that in the tepid group (2.40+/-0.32 vs. 1.85+/-0.21 log(10) (pg/ml), P=0.005). Only nitric oxide showed a significant negative correlation with the systemic vascular resistance index both during and after cardiopulmonary bypass (r=-0.60, P<0.0001) as compared with prostaglandin E(2) and bradykinin. CONCLUSIONS: These findings demonstrated that serum nitric oxide levels in tepid cardiopulmonary bypass were significantly higher than those in hypothermic cardiopulmonary bypass. Nitric oxide correlated with systemic vascular resistance. Thus, nitric oxide may play a pivotal role in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

Biomarkers↗

Active cell migration in retransplanted rat cardiac allografts during the course of chronic rejection.

BACKGROUND: Chronic allograft vasculopathy (CAV) is caused by the infiltration of host immune cells to a graft, but it has been technically difficult to monitor the movements of the cells in graft rejection. METHODS: We used a male-specific gene, SRY, as a marker to investigate the dynamics of host cells in a model of CAV in which immunosuppression was unnecessary and anti-male responses were practically negligible. Fluorescent-based real-time quantitative polymerase chain reaction (PCR) was adapted to estimate the fraction of host cells in a graft by the ratio of SRY to IL-2 gene. Using this technique, we studied the turnover and migration of host cells during the course of CAV progression by retransplanting female allografts from male to female or from female to male rats. RESULTS: We detected histologic CAV 60 days after retransplantation in allografts retransplanted to the F(1) progeny of donor x recipient on the 5th day, but not in those retransplanted on the 3rd day, regardless of the mismatches in the genders. Most of the initial infiltrating cells disappeared rapidly in both cases. The fraction of migrating cells from the second recipient, however, continuously increased in allografts developing CAV, and 60 days after retransplantation exceeded 50%, whereas it stayed at 5% to 15% in those not developing CAV. ED-1-positive macrophages/monocytes were likely candidates for the migrated cells. CONCLUSION: We have developed a simple method to measure the migration of host cells into a graft. This technique was useful, at least in certain rat strains, to investigate the cellular mechanisms of chronic cardiac allograft rejection.

Animals↗

A novel method of species identification using human muscle-specific beta-enolase.

A novel method of species identification using a sensitive sandwich enzyme immunoassay for human muscle-specific beta-enolase was used to analyze bloodstains and skeletal muscle. Human beta-enolase is detectable in human blood at dilutions up to 3 x 10(3) and human muscle extract (0.1 g/ml) at dilutions up to 5 x 10(6) using a sandwich enzyme immunoassay. The cross-reactivities of both blood and skeletal muscle extracts from other species were 0.01 or less. When human skeletal muscle extract was added in a final concentration of 10 mg/ml, the ratio of beta-enolase to total protein in bloodstains was approximately 1000, whereas the addition of skeletal muscle extract of other species resulted in a ratio of less than 10. Application of this method in a practical case proved that human muscle-specific beta-enolase as a marker for species identification is very effective in forensic practice.

Journal Article↗

Changes in mRNA expression levels of synaptic- and target tissue-specific proteins after organophosphate exposure.

We examined the effects of organophosphate exposure on mRNA expression levels of synaptic- and target tissue-specific proteins in rats. We treated rats with a single dose of Disulfoton (O,O-diethyl S-2-ethylthioethyl phosphorodithioate) and used quantitative reverse transcription-polymerase chain reaction (RT-PCR) to measure the time course of changes in the levels of mRNAs encoding acetylcholinesterase (AChE), nicotinic acetylcholine receptor (nAChR), beta-enolase (MSE), and gamma-enolase (NSE) in soleus muscles and sciatic nerves. The expression levels of synaptic genes encoding AChE in both tissues were significantly decreased, with a nadir at 12h after the administration, and this down-regulation lasted for up to 30 days after administration. Similarly, the level of nAChR mRNA in soleus muscle also decreased, with a nadir at 48 h after administration and a return to 95% of that of the control levels by 30 days after administration. These results indicate that administration of organophosphate can decrease AChE and nAChR expression in the neuromuscular junction, and are suggestive of multiple mechanisms of down-regulation of both AChE and nAChR, some of which might involve alterations at the transcriptional level. The transcript level of the target tissue-specific gene encoding MSE in soleus muscle was slightly decreased, with a nadir at 48 h after administration, and was still lower than that of the control level after 30 days. In contrast, the level of the NSE transcript in sciatic nerve significantly increased within 2 h, and this up-regulation was sustained until 30 days after administration. Although the functions of either of these enolases are not completely established, up-regulation of NSE mRNA may be a marker for the nervous system abnormality following organophosphate exposure. All of these phenomena may contribute to the long-lasting neurotoxic effects observed after developmental exposure to organophosphates.

Journal Article↗

Aggregate formation of rCHO cells and its maintenance in repeated batch culture in the absence of cell adhesion materials.

Aggregate formation of recombinant Chinese hamster ovary (rCHO) cells capable of producing granulocyte colony-stimulating factor (G-CSF), using medium lacking cell adhesion materials in a repeated batch culture, was examined together with cell growth, cell viability and G-CSF production. The rCHO culture was conducted in a rotary shaker and the medium was changed every five days. The formation of stable cell aggregates with high reproducibility was observed after the first medium change. The size of the cell aggregates (consisting of several 10s to 40,000 cells) formed during the repeated batch culture ranged from 30 to 600 microm. The cell density of the aggregates reached as high as 2 x 10(6) cells/ml and the viability was maintained at more than 80% for 19 d. Changing the medium to avoid glucose exhaustion effectively maintained the cell density, cell viability and G-CSF productivity at high levels.

Journal Article↗

Lack of antibody production against Hanganutziu-Deicher (H-D) antigens with N-glycolylneuraminic acid in patients with porcine exposure history.

The significance of non-alphagalactosyl antigens remains unclear in pig-to-primate xenotransplantation. Hanganutziu-Deicher (H-D) antigens with terminal N-glycolylneuraminic acid (NeuGc) are widely expressed on endothelial cells of mammalian species, with the exception of humans. As baboons and monkeys also express H-D antigens, a pig-to-non-human primate experimental model cannot resolve the question of whether H-D antigens can elicit a potent humoral response in human recipients. The purpose of this study was to elucidate the clinical significance of H-D antigens by examining the sera from patients who have been previously exposed to porcine tissue. After the digestion of porcine aortic endothelial cells (PAEC) by neuraminidase, NeuGc and N-acetylneuraminic acid (NeuAc) were quantitated by HPLC. IgG and IgM antibody levels against H-D antigens were measured by NeuGc-GM3-coated ELISA plates in the sera of patients who had undergone ex vivo kidney perfusion 1 to 3 weeks and 2 years previously (n=2) or had been injected with fetal porcine islets 2 months previously (n= 10). HPLC determined that 9.7x 10(7) NeuAc and 6.3x 10(7) NeuGc residues per cell were released from PAEC by neuraminidase, while 25.7x 10(7) NeuAc and an undetectable level of NeuGc were released from human aortic endothelial cells (HAEC). No significant elevation of IgG or IgM antibody levels against NeuGc-GM3 was observed in sera from patients with a history of porcine exposure. Considering the active production of antibody against the foreign galactosyl antigens after pig-to-human xenotransplantation, some production of antibodies against the equally foreign H-D antigens would be expected, because large amounts of NeuGc terminated saccharides are present in the pig endothelial cell surface. However, no production of antibodies directed to H-D antigens could be found in patients exposed to porcine tissue. Further studies are warranted to explain why H-D antigens do not elicit a significant antibody production.

Animals↗

Nerve growth factor prevents apoptosis of cord blood-derived human cultured mast cells synergistically with stem cell factor.

BACKGROUND: Stem cell factor (SCF) has been identified as a critical survival factor of human mast cells. Other cytokines which possess survival promotion activity on human mast cells are less known. OBJECTIVE: We examined the survival promotion activity of nerve growth factor (NGF) on cord blood-derived human cultured mast cells. METHODS: Expression and function of NGF receptors on the mast cells were examined by RT PCR, flowcytometric analysis, immunoprecipitaion and western blotting. The survival promotion activity of NGF to the mast cells was examined. To evaluate the proliferating activity of NGF on the human cultured mast cells, flow cytometric analysis with propidium iodide staining was applied. To confirm whether the human mast cell growth activity of NGF was caused by a suppression of apoptosis, the proportion of the cells containing in situ DNA fragmentation was counted. RESULTS: The human cultured mast cells expressed the high affinity receptor p140trk but not the low affinity receptor p75LNGFR. NGF induced the phosphorylation of p140trk. NGF alone could not support the survival of the mast cells, however, the addition of NGF to the culture medium containing recombinant SCF led to a significant increase of the number of survival mast cells. No significant changes of the cell cycle from G0/G1 phase to the S/G2 + M phases were observed by NGF. In contrast, the addition of NGF to the medium with SCF showed a significant inhibitory effect on the apoptosis of the mast cells. CONCLUSION: NGF may act as a key factor to promote the survival of human mast cells synergistically with SCF through the prevention of apoptosis.

Apoptosis↗

Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-gamma).

Thymoma is known to contain CD4+CD8+ T cells, indicating that neoplastic epithelial cells of thymoma have a function as thymic cortical epithelium. However, it has been shown that there is an impairment of CD4+ T cell development in thymoma and that IFN-gamma-induced HLA-DR expression on cultured thymic epithelial cells (TEC) derived from thymoma is decreased when compared with the normal thymus. MHC class II transactivator (CIITA) is known to play a critical role in IFN-gamma-induced MHC II expression. In this study, we attempted to elucidate whether CIITA is responsible for the impaired up-regulation of MHC II molecules in response to IFN-gamma in thymoma TEC. A quantitative reverse transriptase-polymerase chain reaction examination revealed that the induced level of CIITA was significantly lower in thymoma TEC than in normal TEC. The induced levels of invariant chain (Ii) and HLA-DR in thymoma TEC were correlated with CIITA expression. The proportion of CD3+ cells in the CD4+CD8- subset in thymoma was also correlated with CIITA expression. A gel mobility shift assay however, revealed translocation of STAT1 to the nucleus in thymoma as well as normal TEC. Intercellular adhesion molecule-1 was up-regulated in the thymoma TEC to a level similar to normal TEC in response to IFN-gamma. These results indicate that impaired up-regulation of HLA-DR in response to IFN-gamma results from insufficient induction of CIITA, but not from the signal from IFN-gamma receptor to the nucleus. The abnormal regulation of HLA-DR expression caused by impaired induction of CIITA may affect CD4+ T cell development in thymoma.

Adolescent↗

Suspected intestinal myiasis due to Dryomyza formosa in a Japanese schizophrenic patient with symptoms of delusional parasitosis.

A third-stage larva of Dryomyza formosa (Wiedemann) (Diptera: Dryomyzidae) was found in the fresh stool of a 27-year-old Japanese woman resident of Shiobara, 150 km north of Tokyo, on 16 November 1998. This is the first record of myiasis due to Dryomyza. Detection of this maggot (2cm long) by the patient herself was associated with her longstanding delusion of abdominal parasitosis as a symptom of chronic schizophrenia. Circumstantial evidence agreed with this being a genuine case of intestinal myiasis, apparently due to accidental ingestion of the insect, with no signs that the patient had contrived the report, nor that the maggot had invaded the stool post-defaecation. This case draws attention to the likelihood that some personality states are predisposed to noticing and reporting myiasis, when it occurs. We review other conditions (mental and physical) that are more prone to myiasis.

Adult↗

Characterization of antibody responses against rectal mucosa-associated bacterial flora in patients with ulcerative colitis.

BACKGROUND: Previous reports on faecal microflora have demonstrated that the total number of aerobes and coliforms was increased in patients with ulcerative colitis (UC). Based on the hypothesis that the pathogenesis of UC may be closely associated with the mucosal microflora, we investigated alterations in the mucosa-associated microflora of UC patients. METHODS AND RESULTS: The bacterial counts for both aerobes and anaerobes increased in UC patients. In particular, we detected the highest bacterial counts of Bacteroides vulgatus and these bacteria were isolated most frequently. In addition, we also investigated the serum antibody responses against the bacteria isolated from the affected mucosa by serum bacterial agglutination tests and immunoblotting. A high agglutination titre against B. vulgatus, Bacteroides fragilis, and Clostridium ramosum was detected in most UC patients, and the percentage of positive immunoreactivity was much higher in UC patients than in healthy controls. From the results of the immunoblotting, a unique antigenic determinant of B. vulgatus (BV43-26), a 26-kDa protein from the outer membrane, was discovered. The serum immunoreactivity (immunoglobulin (Ig) G) against this 26-kDa protein was much higher in UC patients (53.8%) than in the control sera (9.1%). The serum immunoreactivity (IgG) against a 50-kDa protein isolated from the whole cell protein of Escherichia coli (EC48-1) was also higher in UC patients (29.2%) than in normal controls (6.3%). CONCLUSIONS: These results suggest that B. vulgatus and a specific antibody response directed against it may play an important role in the pathogenesis of UC.

Adolescent↗

Hyperperfusion in the lateral temporal cortex, the striatum and the thalamus during complex visual hallucinations: single photon emission computed tomography findings in patients with Charles Bonnet syndrome.

We report the findings of single photon emission computed tomography using 123I-IMP and magnetic resonance image studies of five patients with Charles Bonnet syndrome (CBS) while they were having visual hallucinations. All patients developed complex visual hallucinations after suffering from eye disease. The mean age at onset of CBS was 71.6 years. Single photon emission computed tomography studies in all patients disclosed hyperperfusion areas with some asymmetrical appearances in the lateral temporal cortex, striatum and thalamus. These results suggest that when elderly people suffer from eye disease, subsequent excessive cortical compensation in the lateral temporal cortex, striatum and thalamus may precipitate the development of visual hallucinations.

Aged↗

Quantitative single photon emission tomography analysis for the diagnosis of transient global amnesia: adaptation of statistical parametric mapping.

We report two cases of transient global amnesia (TGA) diagnosed using a clinical criteria and single photon emission tomography (SPECT) with the aid of Statistical Parametric Mapping (SPM). Both patients underwent an initial SPECT study about 20 h after the disappearance of the amnesic episode, and a second study 3 weeks after the episode. We conducted quantitative cerebral blood flow (CBF) analyses using SPM on Matlab. This revealed regions with abnormal CBF in the first studies but not in the second. This method appears to be useful for diagnosis of TGA, especially in patients with suspected TGA in whom the amnesic episode disappears within a few days.

Aged↗

P-selectin participates in cardiopulmonary bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production.

OBJECTIVES: P-selectin participates in the development of inflammatory disorders. Cardiopulmonary bypass is thought to induce inflammatory response and increase nitric oxide production. To evaluate the role of P-selectin in bypass-induced inflammatory response and its association with nitric oxide production, we examined the effect of P-selectin monoclonal antibody in a rat model of cardiopulmonary bypass. METHODS: Twenty adult Sprague-Dawley rats undergoing cardiopulmonary bypass for 60 minutes were divided into 2 groups. A 3-mg/kg dose of anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumitomo Pharmaceuticals, Osaka, Japan) was administered into the priming solution before bypass in group P (n = 10) and a 3-mg/kg dose of PNB1.6 (nonblocking monoclonal antibody) was added in group C for control (n = 10). RESULTS: At the termination of bypass and 3 hours after the termination of bypass, plasma levels of interleukins 6 and 8, nitrate/nitrite, the percentage ratio of nitrotyrosine to tyrosine (an indicator of peroxynitrite formation), and the respiratory index were significantly higher than before bypass in both groups, and they were significantly lower in group P than in group C. Plasma P-selectin level in group C and exhaled nitric oxide concentration in both groups at termination of bypass were significantly lower than those before bypass, and they were significantly higher 3 hours after termination of bypass than before bypass in both groups. Plasma P-selectin level and exhaled nitric oxide concentration in group P were significantly higher than those in group C at the end of bypass, but they were significantly lower 3 hours after the termination of bypass. CONCLUSIONS: These results demonstrate that P-selectin may participate in the augmentation of bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production.

Animals↗

Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice.

We investigated the antihyperglycemic action of a crude saponin fraction and five triterpene glycosides (gymnemic acids I-IV and gymnemasaponin V) derived from the methanol extract of leaves of Gymnema sylvestre R. BR. (Asclepiadaceae) in streptozotocin (STZ)-diabetic mice. The saponin fraction (60mg/kg) reduced blood glucose levels 2 4h after the intraperitoneal administration. Gymnemic acid IV, not the other 4 glycosides at doses of 3.4-13.4mg/kg reduced the blood glucose levels by 13.5-60.0% 6h after the administration comparable to the potency of glibenclamide, and did not change the blood glucose levels of normal mice. Gymnemic acid IV at 13.4 mg/kg increased plasma insulin levels in STZ-diabetic mice. Gymnemic acid IV (1 mg/mL) did not inhibit alpha-glycosidase activity in the brush border membrane vesicles of normal rat small intestines. These results indicate that insulin-releasing action of gymnemic acid IV may contribute to the antihyperglycemic effect by the leaves of G. sylvestre. Gymnemic acid IV may be an anti-obese and antihyperglycemic pro-drug.

Animals↗