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Biomedical subjects

M Nishiyama

Publications and source records attributed to M Nishiyama.

At least 55 records · Page 3Linked to original sources

Analysis of T wave changes by activation recovery interval in patients with atrial septal defect.

We examined the distributions of the activation recovery interval (ARI), which is correlated with the local action potential duration (APD), to clarify the origin of the repolarization changes in ASD. The ECGs, QRST isointegral maps and ARI isochronal maps of 21 children with ASD from 3 to 5 years old in age were studied in comparison with 21 age-matched normal children. A conventional and 87 unipolar body surface ECG were simultaneously recorded. The ARIs were determined from the first derivatives of the ECG waveforms. Abnormal ST-T patterns were observed in 11 of 21 ASD, but only in two normal children. The QRST maps of a split positive area pattern were seen in 15 of ASD but none of the normal. In the ARI maps, all the normal children exhibited a short-ARI area on the left and a long-ARI area on the right side of the chest. In 19 of ASD, the ARI distribution revealed a leftward extension of the long-ARI area on the anterior chest, a relative shortening on the right anterior chest, and a localized prolonged ARI on the left anterior chest. The results suggest that right ventricular (RV) volume overload in ASD produces a localized prolongation of the APD on the RV epicardium.

Child, Preschool↗

Calcium signalling in the guidance of nerve growth by netrin-1.

Pathfinding by growing axons in the developing nervous system is guided by diffusible or bound factors that attract or repel the axonal growth cone. The cytoplasmic signalling mechanisms that trigger the responses of the growth cone to guidance factors are mostly unknown. Previous studies have shown that the level and temporal patterns of cytoplasmic Ca2+ can regulate the rate of growth-cone extension in vitro and in vivo. Here we report that Ca2+ also mediates the turning behaviour of the growth cones of cultured Xenopus neurons that are induced by an extracellular gradient of netrin-1, an established diffusible guidance factor in vivo. The netrin-1-induced turning response depends on Ca2+ influx through plasma membrane Ca2+ channels, as well as Ca2+-induced Ca2+ release from cytoplasmic stores. Reduction of Ca2+ signals by blocking either of these two Ca2+ sources converted the netrin-1-induced response from attraction to repulsion. Activation of Ca2+-induced Ca2+ release from internal stores with a gradient of ryanodine in the absence of netrin-1 was sufficient to trigger either attractive or repulsive responses, depending on the ryanodine concentration used. These results support the model that cytoplasmic Ca2+ signals mediate growth-cone guidance by netrin-1, and different patterns of Ca2+ elevation trigger attractive and repulsive turning responses.

Animals↗

Electrocautery snare resection stimulates cellular proliferation of residual colorectal tumor: an increasing gene expression related to tumor growth.

PURPOSE: Recently, endoscopic mucosal resection has been performed commonly for colorectal tumors. However, incomplete endoscopic mucosal resection produces a residual tumor that grows rapidly. The aim of this study was to clarify the characteristics of the residual tumor using the nude mouse model. METHODS: Human colon cancer cells (colo201 or colo320DM) were implanted subcutaneous into nude mice. We then removed more than one-half of the tumor with an electrocautery snare or a surgical knife, and compared the tumor growth rate with that of control tumors. Before and after resection, we examined the Ki-67 labeling index of the tumors with an immunohistochemical assay and mRNA expression for epidermal growth factor receptor, vascular endothelial growth factor, and transforming growth factor alpha. RESULTS: Residual tumors showed a higher growth rate in tumor volume than control tumors using both methods (electrocautery snare and surgical knife). Colo201 groups showed a higher total volume change per day than colo320DM groups after resection. Furthermore, these tumors also showed a higher Ki-7 labeling index, and a stronger epidermal growth factor receptor and transforming growth factor alpha mRNA expression than primary and control tumors in the colo201 implanted groups. There was no significant difference in vascular endothelial growth factor mRNA expression between groups implanted with colo201 or colo320DM. CONCLUSION: Our results suggest that residual tumors caused by incomplete endoscopic mucosal resection may have a higher growth potential than the tumors before resection.

Animals↗

What is characteristic of fungal lysine synthesis through the alpha-aminoadipate pathway?

Recent finding that a prokaryote synthesizes lysine through the alpha-aminoadipate pathway demonstrates that the lysine synthesis through the alpha-aminoadipate pathway is not typical of fungi. However, the fungal lysine biosynthesis is not completely the same as the prokaryotic one. We point out that alpha-aminoadipate reductase is a key enzyme to the evolution of fungal lysine synthesis. In addition, fungi have two different saccharopine dehydrogenases, which is also characteristic of fungi.

2-Aminoadipic Acid↗

Regulation of type-2 corticotropin-releasing hormone receptor mRNA in rat heart by glucocorticoids and urocortin.

A novel subtype of corticotropin-releasing hormone (CRH) receptor, designated type-2 CRH receptor (CRHR-2), has been cloned by a number of laboratories, and its mRNA has been found to be distributed not only in the brain but in peripheral tissues such as heart and skeletal muscle. To date, however, the regulation of CRHR-2 mRNA is poorly understood. Therefore, we examined the effect of glucocorticoid treatment, adrenalectomy, and systemic administration of urocortin, a possible endogenous ligand for CRHR-2, on heart CRHR-2 mRNA levels in male Wistar rats, using in situ hybridization histochemistry. CRHR-2 mRNA in the heart was significantly decreased 9 h after systemic administration of urocortin (5 microg/kg b.w.). Systemic administration of corticosterone (CORT; 10 mg/rat/day for 12 days) or CORT pellet (200 mg) implant for 7 and 14 days also decreased CRHR-2 mRNA in the heart, whereas it was unchanged 7 days after adrenalectomy. Thus, similar regulation of CRHR-2 mRNA in the rat heart by its ligand and glucocorticoids was observed. The precise mechanism of the regulation of CRHR-2 mRNA in the heart and the physiologic significance of cardiac CRHR-2 remains to be elucidated.

Adrenalectomy↗

Glucocorticoid effects on the diurnal rhythm of circulating leptin levels.

It is known that circulating leptin shows diurnal variation with a nocturnal rise; however, the mechanisms generating this rhythm have not been fully elucidated. Glucocorticoids are a potent stimulator of leptin secretion, and there is a reciprocal relationship between circulating leptin and glucocorticoid levels. We hypothesized that glucocorticoids could modulate the diurnal rhythm of circulating leptin. We therefore explored the diurnal variation of leptin under situations in which subjects showed no or some shift of glucocorticoid diurnal rhythm, such as prednisolone-administered humans, and adrenalectomized and corticosterone-replaced (ADX+B) rats. The peak level of plasma cortisol immunoreactivity was shifted from early morning to noon by prednisolone administration. The nocturnal increment of plasma leptin in prednisolone-administered patients (71.2 +/- 14.2% from 08:00 h value) was significantly greater than that in normal volunteers (12.2 +/- 7.5% from 08:00 h value), but the timing of nadir and the peak of plasma leptin was not shifted. In normal rats, the plasma concentration of leptin showed the diurnal rhythm with the bottom at 16:00 h and the top between midnight and early morning. The amplitude of leptin diurnal rhythm was significantly reduced in ADX+B rats (08:00 h: 3.0 +/- 0.2, 16:00 h: 2.7 +/- 0.2, 00:00 h; 3.7 +/- 0.2 ng/ml) compared with sham operated rats (08:00 h: 3.0 +/- 0.2, 16:00 h 2.2 +/- 0.2, 00:00 h: 4.7 +/- 0.4 ng/ml); but ADX+B rats still retained similar timing of nadir and the peak of plasma leptin as observed in sham rats. These results indicate that glucocorticoids enhance the amplitude of leptin diurnal rhythm, and are consistent with previous findings showing that glucocorticoids increase leptin secretion. Glucocorticoids appear to play modulatory, but not essential roles in generating leptin diurnal rhythm.

Adrenalectomy↗

Splice isoforms of transcription factor Elf-1 affecting its regulatory function in transcription-molecular cloning of rat Elf-1.

To elucidate the role of Elf-1 in Fc epsilonRI alpha chain expression, rat Elf-1 cDNAs were isolated and characterized. The rat Elf-1 cDNA of 2744 bp contained an open reading frame of 1848 bp. In addition to the full length rat Elf-1 cDNA (named type 1), two splice isoforms were isolated. One of the two isoforms lacked the amino acid residues from 85th to 120th (type 2), and the other from 85th to 175th (type 3). Similar isoforms were also observed in human tissue. Overexpression of rat Elf-1 (type 1) using a transient coexpression system inhibited of the alpha chain promoter activity. The inhibition activity was different between the isoforms; the inhibition activity of type 2 was lower than that of type 1, and type 3 did not have an inhibitory effect. This observation suggested that each Elf-1 isoform played a different role in the gene expression under its control.

Amino Acid Sequence↗

Gene organization for nitric oxide reduction in Alcaligenes faecalis S-6.

norB and norC encoding the cytochrome b-containing subunit and the cytochrome c-containing subunit, respectively, of the nitric oxide reductase (NOR) in Alcaligenes faecalis S-6 were cloned and sequenced. Both NorB and NorC showed more than 40% sequence identity to the corresponding subunits of cytochrome bc-type NORs in other denitrifying bacteria. norCB was in a gene cluster containing seven other genes; these were named dnr, orf2, orf3, norE, norF, norQ, and norD on the basis of their similarity with NOR systems in other bacteria. Potential FNR-binding sites were present in front of norCB, norEF, and/or orf2/orf3, suggesting that most of these genes are regulated simultaneously by an FNR-related protein. NorB and NorC proteins produced in the membrane fraction in Escherichia coli showed no enzyme activity, probably due to lack of NorQ and NorD, which appear to perform some essential function for activation of the NorB-NorC complex in the recombinant E. coli.

Alcaligenes↗

Detection rates of TT virus DNA in serum of umbilical cord blood, breast milk and saliva.

To date, the routes of mother-to-infant transmission of TT virus (TTV) have not been fully elucidated. The present study examines the detection rates of TTV DNA in the serum of pregnant Japanese women and in cord blood at the time of delivery, as well as in the saliva and breast milk of mothers one-month postpartum. Primers derived from the well-known translated region N22 (N22 system), as well as the untranslated region (UTR system) were used. The prevalence of TTV DNA in the serum of pregnant women was found to be 11.9% (19/160) using the N22 system and 72.4% (55/76) using the UTR system. No TTV DNA was detected in the cord blood samples (0/160) when the N22 system was used for detection but TTV DNA was detected in 11.8% (7/76) of samples studied with the UTR system. Using the N22 system, TTV DNA was not detected in breast milk, but was detected in saliva. However using the UTR system, TTV DNA was detected in both specimens. These results imply that some babies are vertically infected with TTV via cord blood at the time of delivery or via breast milk or saliva. However, further research is necessary to confirm this hypothesis. polymerase chain reaction; pregnant women; horizontal route of transmission

Adult↗

Apolipoprotein E, methylenetetrahydrofolate reductase (MTHFR) mutation and the risk of senile dementia--an epidemiological study using the polymerase chain reaction (PCR) method.

We examined apolipoprotein E (Apo E) polymorphism and methylenetetrahydrofolate reductase (MTHFR) 677 C to T mutation by using the polymerase chain reaction (PCR) method in 100 elderly Japanese aged 60 or more, and assessed whether these genetic factors are associated with an increased risk for the clinical phenotypes of senile dementia, Alzheimer's disease (AD) and vascular dementia (VD) by cross-sectional survey. It was found that the Apo E epsilon 4 allele were associated with an increased prevalence of AD as previously reported. Although, it was not strongly related to the severity of senile dementia, a weak association between the ApoE genotype and the severity of dementia was suggested. The proportion of patients with senile dementia was higher in the group of carriers of MTHFR mutation than in the group of noncarriers. Furthermore, the proportion of male patients with senile dementia was higher in the group of homozygous for the mutation (+/+) than the group without the mutation (-/-). Notably in VD patients, 5 of 7 males had the +/+ genotype. The results suggest that the ApoE epsilon 4 genotype and the MTHFR mutation are associated with the clinical phenotype and the clinical onset of senile dementia.

Aged↗

The human behavioral and socioeconomic determinants of malaria in Bacan Island, North Maluku, Indonesia.

In eastern Indonesia, malaria control activities mainly depend on residual spraying but the situation is almost unchanged since the past decade. Understanding the socioeconomic and human behavior determinants is needed to implement an effective malaria control in accordance with the local condition and development. Hence we conducted an unmatched case control study. Two hundred samples were recruited from all, 11 villages surrounding the centre in Bacan Island, Maluku. For children aged 0 to 15 years old, the association of socioeconomic determinants: crowding and poor type of houses with malaria remained significant in the multivariate analysis. Meanwhile for persons above 15 years old, younger persons and regular going outside at night remained significant in the multivariate analysis. And for persons above 15 years old, a higher proportion of controls (14%) than cases (4%) slept under mosquito net regularly. The Indonesia Family Program should be promoted. There was a better quality of life in small family. For persons above 15 years old, going outside at night should be discouraged because exposed to mosquito bites. The malaria control strategy use of effective personal, regular use of mosquito net could be used as a completion for the present activities. Considering the low malaria knowledge among samples, inhabitants should be enhanced the malaria knowledge on causation, transmission, prevention and to provide proper knowledge on residual spraying.

Adolescent↗

RGS domain in the amino-terminus of G protein-coupled receptor kinase 2 inhibits Gq-mediated signaling.

We have previously shown that not only G protein-coupled receptor kinase (GRK) 2, but also a catalytically inactive Lys220Trp GRK2 decreases endothelin (ET)-1-induced inositol 1,4,5-trisphosphate (IP3) formation, and demonstrated the presence of phosphorylation-independent desensitization mechanism. To clarify the role of GRK2 other than that as a kinase, we characterized an RGS (regulator of G protein signaling)-like domain in the amino-terminus of GRK2. Both GRK2(1-181) and GRK2(54-174) suppressed Ca2+ responses induced by angiotensin II (Ang II) and ET-1, and bound directly with Galphaq but not Galphas nor Galphai3 in the presence of GDP and AlF4-. These results demonstrate that GRK2 regulates Gq-mediated signaling negatively by direct interaction between its RGS domain and the transitional state of Galphaq, as well as through phosphorylation of activated receptors by its kinase domain.

Aluminum Compounds↗

NADPH/quinone oxidoreductase is a priority target of glioblastoma chemotherapy.

We attempted to determine a target of chemotherapy specific to glioblastoma cells to ensure a favorable response to anticancer drugs, through comparison in biologic nature related to drug resistance with other types of cancer cells. Using 13 human cancer cell lines including 3 glioblastoma lines, gene expression analysis and biochemical quantitative assay were performed for a total of 12 properties, which have been linked to drug action. Although most of genes related to drug resistance, such as MDR1, MRP, MGMT and GSTpi, were overexpressed in T98G, U-373MG, and U-251MG glioblastoma cells, Topo I (topoisomerase I) expression was relatively low and alpha- and beta-TUB (tubulin) expression was comparable to other types of 10 cell lines. The glioblastoma cell lines also showed an increased expression of NADPH/quinone oxidoreductase gene (NQO1), but the respective enzyme NQO activated MMC. Among the drugs targeting such properties, MMC was more active than Topo I inhibitors and docetaxel (TXT) due to the lack of other sensitivity (resistance) determinants. Differing from MMC, MGMT was shown to participate in the resistance of Topo I inhibitors (CPT-11, SN-38 and DX-8951f), while GSTpi and MDR1 were involved in docetaxel (TXT) resistance. MMC was also more active than ACNU and CDDP in the three glioblastoma cells. NQO may be a priority target of glioblastoma chemotherapy suitable for biochemical nature of the cells, and expression analysis of NQO1, alpha-TUB, beta-TUB, MGMT, MDR1 and GSTpi may help to seek a truly active drug against glioblastomas.

Antineoplastic Agents↗

[Current status of "low-dose cisplatin-5-FU therapy" for solid tumors (2nd report)--from a nationwide questionnaire on its adverse effects].

A nationwide questionnaire survey was carried out on low-dose cisplatin-5-FU therapy for solid malignant tumors (mostly stomach and colon cancer) regarding its antitumor as well as adverse effects. The regimen was defined as 4 weeks administration of cisplatin 2-5 mg/body, 5 days a week, which was used in 47% of 82 institutions studied. Cases were classified into an Ab regimen (86 cases) with cisplatin 3-5 mg/body, and a Bb regimen (122 cases) with cisplatin 6-30 mg (mostly 10 mg)/body, both of which were given 5-FU 300-500 mg/body daily. The antitumor effect (CR + PR) was shown to be slightly higher in the Bb regimen than in the Ab regimen, and was 35% overall. Very few adverse effects appeared with either regimen for mostly major digestive, hepatic and renal functions, except for myelodepressions (leucopenia and thrombocytopenia), which were more than grade 3 in only a few percent with the Ab regimen, and a little more than 10% with the Bb regimen. The advantages and disadvantages of the A/Bb regimens appeared to be counter-balanced in terms of their antitumor and adverse effects. Most institutions using the Ab regimen favored repeating the regimen cycle as much as possible. Those using more than 6 cycles accounted for about 20% of hospitals.

Antimetabolites, Antineoplastic↗

[The clinical effect of low-dose FP (5-FU + low-dose CDDP) in patients with far advanced gastric cancer, and their quality of life].

Low-dose FP therapy was carried out in 30 patients with far advanced gastric cancer and assessed according to anti-tumor effect and quality of life (QOL). This therapy consisted of CDDP (3.5-7 mg/m2/day infused on Days 1-5 every week) and continuous infusion of 5-FU (250 mg/m2/day for 28 days). A partial response was observed in 15 cases, so the overall response rate was 50%. The response rates with stomach and lymph node cancers were higher than those of other organs (64.3% and 55.6%). Patients without peritoneal dissemination, with good performance status (PS) (0, 1) and differentiated histologic type showed a significantly higher response rate than patients with peritoneal dissemination, poor PS (2, 3, 4) and undifferentiated histologic type (p = 0.0034, 0.0253, 0.0080). No side effects (> or = WHO grade 3) were observed. The QOL of patients was assessed according to the percentage of patients with an observed improvement of diet, who could be discharged from hospital, and the duration in hospitals in relation to survival time (hospital stay). The QOL of patients with low-dose FP therapy was better than that of patients with usual combination chemotherapy. Low-dose FP therapy is a promising regimen for patients with far advanced gastric cancer.

Adenocarcinoma↗

The comparison of tuberculosis treatments: a short course therapy and the directly observed short course treatment (DOTS), East Java Province, Indonesia.

Tuberculosis has been given great attention as HIV/AIDS has increased. Because HIV causes a higher tuberculosis risk is becoming more and more important better tuberculosis treatment. This study aimed to compare the smear conversion rate between short course therapy and the tuberculosis treatment with directly observed short course therapy (DOTS), in East Java, Indonesia. The average smear conversion rate in short course therapy among 35,292 cases was 94.40% over 5 year period (1989/90-1993/94). The tuberculosis treatment with DOTS was started in 1994/95. In the first 2 years the smear conversion rate were 97.67% (42/43) and 98.00% (196/200), respectively. The smear conversion rate of the treatment with DOTS was significantly higher compared to a short course therapy (p-value: <0.001). Thus, tuberculosis treatment with DOTS should be promoted. The concept of supervision by health workers or health cadres should be applied considering mostly are given by family members. And there should be readiness of tuberculosis staff to do the treatment with DOTS in all levels to expand the coverage.

Antitubercular Agents↗