Quantitative imaging of substance P in the human brain using a brain mapping analyzer.
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Journal Article↗
Biomedical subjects
K Yabe
Publications and source records attributed to K Yabe.
Age-related changes in gait velocity and leg extension power in middle-aged and elderly people.
To prevent a decline in gait with age, it is necessary to investigate age-related changes in gait performance and detect related factors. The purpose of this study was to assess the association between gait ability and leg extension power among middle-aged and elderly people. Height, weight, maximum gait velocity (MGV) and leg extension power (LEP) were measured in 752 males and females who participated in the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). Age-related changes in MGV and LEP and the association between MGV and LEP were assessed. There were significant decline trends in height, weight, MGV and LEP with advancing age (p < 0.001). MGV showed a significantly positive correlation with LEP (in males: r = 0.48 p < 0.001, in females: r = 0.47; p < 0.001). Subjects aged 60 yrs and over showed a significantly higher correlation than those under 60 yrs in males, but not in females, after adjustment for height and weight. Although the relationships between MGV and LEP were different by age and gender, LEP may be one of the important factors in maintaining gait ability.
Activities of Daily Living↗
Quantitative imaging of substance P in the human brain using a brain mapping analyzer.
The distribution of substance P (SP)-like immunoreactive neurons in the brains of aged normal human was analyzed quantitatively. Consecutive coronal sections in which the striatum and the substantia nigra were exposed widely, were obtained from the right hemisphere and stained immunohistochemically for SP. Each stained section was divided into approximately three million microareas and the immunohistochemical fluorescence intensity in each area was measured using a human brain mapping analyzer, which is a microphotometry system for analysis of the distribution of neurochemicals in a large tissue slice. These distributions are displayed in color and monochromatic graphics. In the analyzed brain regions, conspicuously intense SP-like immunoreactivity was observed in the substantia nigra and the internal segment of the globus pallidus. Within the substantia nigra, the SP-like immunoreactive intensity in the pars compacta was 25%, higher than that in the pars reticulata, and the distribution of melanin-containing neurons corresponded well to the distribution of the SP-containing structures. SP-like immunoreactive intensity in the internal segment of the globus pallidus, which was lower than that in the substantia nigra, was approximately twice as high as that in the external segment of the globus pallidus. Very intense immunoreactivity was localized at the most medial area of the internal segment of the globus pallidus. The SP-like immunoreactive intensity in the caudate nucleus and putamen was moderate, and the distribution was heterogeneous and observed in patches.
Aged↗
Bone mineral density differences between paraplegic and quadriplegic patients: a cross-sectional study.
STUDY DESIGN: This cross-sectional study was conducted by comparing bone mineral density (BMD) of paraplegic and quadriplegic patients. OBJECTIVES: The purpose of this study was to investigate the relationship between the bone mineral loss and injury level in spinal cord injury patients. SETTINGS: Experiments were conducted at Yoneda Hospital and Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan. METHODS: Lumbar spine (L2-4), proximal femur (femoral neck, trochanter region and Ward's triangle) and whole body BMD were measured in ten paraplegic and ten quadriplegic patients using dual-energy X-ray absorptiometry (DXA, HITACHI BMD-IX). RESULTS: Significant differences were observed in the lumbar spine, trochanter region and upper extremities BMD between paraplegic and quadriplegic patients (P<0.05, P<0.05 and P<0.01, respectively), but not in the femoral neck, Ward's triangle, head, pelvis, lower extremities or whole body BMD. CONCLUSION: These results suggest that the injury level influences on the lumbar spine, upper extremities and trochanter region BMD. From a biomechanical standpoint, it is possible to explain that the differences in mechanical loading exerted on bones also affected the difference of lumbar spine BMD in the two groups.
Absorptiometry, Photon↗
Cloning and characterization of the O-methyltransferase I gene (dmtA) from Aspergillus parasiticus associated with the conversions of demethylsterigmatocystin to sterigmatocystin and dihydrodemethylsterigmatocystin to dihydrosterigmatocystin in aflatoxin biosynthesis.
O-Methyltransferase I catalyzes both the conversion of demethylsterigmatocystin to sterigmatocystin and the conversion of dihydrodemethylsterigmatocystin to dihydrosterigmatocystin during aflatoxin biosynthesis. In this study, both genomic cloning and cDNA cloning of the gene encoding O-methyltransferase I were accomplished by using PCR strategies, such as conventional PCR based on the N-terminal amino acid sequence of the purified enzyme, 5' and 3' rapid amplification of cDNA ends PCR, and thermal asymmetric interlaced PCR (TAIL-PCR), and genes were sequenced by using Aspergillus parasiticus NIAH-26. A comparison of the genomic sequences with the cDNA of the dmtA region revealed that the coding region is interrupted by three short introns. The cDNA of the dmtA gene is 1,373 bp long and encodes a 386-amino-acid protein with a deduced molecular weight of 43,023, which is consistent with the molecular weight of the protein determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The C-terminal half of the deduced protein exhibits 76.3% identity with the coding region of the Aspergillus nidulans StcP protein, whereas the N-terminal half of dmtA exhibits 73.0% identity with the 5' flanking region of the stcP gene, suggesting that translation of the stcP gene may start at a site upstream from methionine that is different from the site that has been suggested previously. Also, an examination of the 5' and 3' flanking regions of the dmtA gene in which TAIL-PCR was used demonstrated that the dmtA gene is located in the aflatoxin biosynthesis cluster between (and in the same orientation as) the omtA and ord-2 genes. Northern blotting revealed that expression of the dmtA gene is influenced by both medium composition and culture temperature and that the pattern correlates with the patterns observed for other genes in the aflatoxin gene cluster. Furthermore, Southern blotting and PCR analyses of the dmtA gene showed that a dmtA homolog is present in Aspergillus oryzae SYS-2.
Aflatoxins↗
Enzymatic formation of G-group aflatoxins and biosynthetic relationship between G- and B-group aflatoxins.
We detected biosynthetic activity for aflatoxins G(1) and G(2) in cell extracts of Aspergillus parasiticus NIAH-26. We found that in the presence of NADPH, aflatoxins G(1) and G(2) were produced from O-methylsterigmatocystin and dihydro-O-methylsterigmatocystin, respectively. No G-group aflatoxins were produced from aflatoxin B(1), aflatoxin B(2), 5-methoxysterigmatocystin, dimethoxysterigmatocystin, or sterigmatin, confirming that B-group aflatoxins are not the precursors of G-group aflatoxins and that G- and B-group aflatoxins are independently produced from the same substrates (O-methylsterigmatocystin and dihydro-O-methylsterigmatocystin). In competition experiments in which the cell-free system was used, formation of aflatoxin G(2) from dihydro-O-methylsterigmatocystin was suppressed when O-methylsterigmatocystin was added to the reaction mixture, whereas aflatoxin G(1) was newly formed. This result indicates that the same enzymes can catalyze the formation of aflatoxins G(1) and G(2). Inhibition of G-group aflatoxin formation by methyrapone, SKF-525A, or imidazole indicated that a cytochrome P-450 monooxygenase may be involved in the formation of G-group aflatoxins. Both the microsome fraction and a cytosol protein with a native mass of 220 kDa were necessary for the formation of G-group aflatoxins. Due to instability of the microsome fraction, G-group aflatoxin formation was less stable than B-group aflatoxin formation. The ordA gene product, which may catalyze the formation of B-group aflatoxins, also may be required for G-group aflatoxin biosynthesis. We concluded that at least three reactions, catalyzed by the ordA gene product, an unstable microsome enzyme, and a 220-kDa cytosol protein, are involved in the enzymatic formation of G-group aflatoxins from either O-methylsterigmatocystin or dihydro-O-methylsterigmatocystin.
Aflatoxin B1↗
Involvement of adenosine receptor, potassium channel and protein kinase C in hypoxic preconditioning of isolated cardiomyocytes of adult rat.
A possible mechanism for hypoxic preconditioning of adult rat cardiomyocytes was pharmacologically investigated. Isolated cardiomyocytes in all experimental groups were incubated for 120 min under hypoxic conditions followed by 15-min reoxygenation (sustained H/R). Sustained H/R decreased rod-shaped cells. Exposure of the cardiomyocytes to 20-min of hypoxia/30-min reoxygenation (hypoxic preconditioning) attenuated the sustained H/R-induced decrease in rod-shaped cells. The effects of hypoxic preconditioning were abolished by treatment with the protein kinase C (PKC) inhibitor polymyxin B, but abolished by neither the adenosine A1/A2-antagonist sulfophenyl theophylline (SPT) nor the ATP-sensitive potassium channel (K(ATP) channel) blocker glibenclamide. In another series of experiments, cardiomyocytes were incubated without hypoxic preconditioning in the presence of either the PKC activator PMA, adenosine or K(ATP)-channel opener nicorandil and then subjected to sustained H/R. Treatment of the cells with PMA, adenosine or nicorandil mimicked the effects of hypoxic preconditioning. The effects of treatment with adenosine and nicorandil were abolished by polymyxin B treatment. Combined treatment with both SPT and glibenclamide abolished the effects of hypoxic preconditioning, whereas it failed to abolish PMA-induced cytoprotection. These results suggest that the activation of PKC in hypoxic preconditioned cardiomyocytes coupled independently with stimulation of adenosine receptor or opening of K(ATP) channel, either of which is fully enough to exert the cytoprotective effects.
Animals↗
[Is portal infusion chemotherapy uneffective for hepatic recurrence after resection for colorectal cancer?].
Sixty-six patients with colorectal cancer were studied regarding effects of prevention of hepatic recurrence in completely performed portal infusion chemotherapy. The regimen was continuous administration of 500-875 mg/body of 5-FU for 7 days and intraportal administration of 10 mg of MMC before and after 5-FU administration. Hepatic recurrence rate was 7.6% and the five year survival rate was 83.3% in portal infusion group, and 16% and 71.3% in the control group; the difference was not significant. However, the hepatic recurrence rate in patients administered more than 4 g of 5-FU was 2.5%; there was a significant difference between the portal group and control group. The five-year survival rate for patients administered more than 4 g of 5-FU was 92.3%, which was significantly higher than at less than 4 g. Excellent effects for prevention of hepatic recurrence and prognosis were obtained in patients administered more than 4 g of 5-FU. Thus, the compliance of 5-FU in portal infusion chemotherapy is important. Also, administration of MMC is suspected to enhance the effect of portal infusion chemotherapy.
Adult↗
Transcript of a homolog of aflR, a regulatory gene for aflatoxin synthesis in Aspergillus parasiticus, was not detected in Aspergillus oryzae strains.
Some strains of Aspergillus oryzae were shown to have homologs of aflR, a regulatory gene for aflatoxin synthesis in Aspergillus parasiticus. Transcription of an aflR homolog was examined in six strains of A. oryzae having the homologs, using polymerase chain reaction (PCR) coupled with reverse transcription. No PCR product was obtained when the RNA prepared from the A. oryzae strains cultivated under aflatoxin-producing condition was used as template for amplification of the aflR cDNA. By contrast, a PCR product of the expected size was obtained with RNA from A. parasiticus NIAH-26 processed by the same procedure. From genomic DNA of these strains, PCR products of the same size as above were obtained. Possible degradation of the aflR mRNA in the RNA preparation of the A. oryzae strains was negligible, because the calmodulin transcript was detected by PCR from the same RNA samples. Thus, the aflR homologs in the non-aflatoxigenic A. oryzae strains examined are not expressed even under aflatoxin-producing condition.
Aflatoxins↗
Quantitative mapping analyzer for determining the distribution of neurochemicals in the human brain.
We developed a human brain mapping analyzer to determine the quantitative distribution of specific molecules, such as neurotransmitters or neuromodulators, based on a fluorescence microphotometry system that we had previously developed. The immunohistochemical fluorescence emitted from each microarea of a brain slice is collected into a photomultiplier tube through the pinhole and objective lens of a microscope. The brain slice is moved in the x- or y-direction by a motorized scanning stage under the objective lens, and the fluorescence intensities are measured quantitatively. The scanning speed is approximately 100 microareas/s, the maximum stage motion is 150 x 150 mm, and an unlimited amount of data can be gathered continuously by transfer to external memory devices. In this paper, this analyzer is characterized in detail, and the methods used for the preparation and analysis of human brain slices are described. As an example, the cholinergic distribution in hemispheric coronal slices of the adult human brain is analyzed. Each slice, immunohistochemically stained for choline acetyltransferase, was divided into approximately 3 million microareas (one area is 50 microm in diameter), and the distribution of the cholinergic neurons is shown.
Aged↗
Beta-casomorphin-5 stimulates neurite outgrowth in a mouse neuroblastoma cell line (Neuro-2a).
We studied the effect of beta-casomorphin-5 (mu-acting opioid peptides derived from milk protein beta-casein) on neurite outgrowth of mouse neuroblastoma cell line, Neuro-2a. Beta-casomorphin-5 stimulated neurite outgrowth of Neuro-2a cells in a naloxone-reversible manner. The stimulating effect of beta-casomorphin-5 was observed even at picomolar concentrations. The selective mu-agonist, (D-Ala2, N-Me-Phe4, Gly5-ol)-enkephalin (DAMGO) exhibited the similar stimulating effect only at micromolar concentrations. On the other hand, (D-Pen(2,5))-enkephalin (DPDPE) (a delta-agonist), U-50,488 (a kappa-agonist), and endogenous opioid peptides, such as enkephalins and dynorphin A (1-13), showed no such stimulating effect. These results suggest that the neurite outgrowth-stimulating action of beta-casomorphin-5 may be mediated via a receptor which has mu-like characteristics and high sensitivity to beta-casomorphin-5, and that beta-casomorphins may play a role as a neurite elongation factor during the suckling period.
Animals↗
Effects of high-intensity resistance training on bone mineral density in young male powerlifters.
The effects of high-intensity resistance training on bone mineral density (BMD) and its relationship to strength were investigated. Lumbar spine (L2-L4), proximal femur, and whole body BMD were measured in 10 male powerlifters and 11 controls using dual-energy X-ray absorptiometry (DXA). There were significant differences in lumbar spine and whole body BMD between powerlifters and controls, but not in proximal femur BMD. A significant correlation was found between lumbar spine BMD and powerlifting performance. These results suggest that high-intensity resistance training is effective in increasing the lumbar spine and whole body BMD.
Absorptiometry, Photon↗
Aspergillus oryzae with and without a homolog of aflatoxin biosynthetic gene ver-1.
Part of the nucleotide sequence of the ver-1 homolog in each of two strains of Aspergillus oryzae, Aspergillus sojae, and Aspergillus flavus were compared with two homologs in Aspergillus parasiticus. The homologs in A. oryzae and A. sojae (non-aflatoxin-producers) exhibited an extremely high degree (93.8-99.8% for A. oryzae, and 96.0-99.5% for A. sojae) of sequence identify with that of A. flavus and A. parasiticus. No two strains within the same species, except A. sojae, were identical. No sequence fingerprint was found to distinguish between A. oryzae and A. flavus, or between A. sojae and A. parasiticus. The predicted partial amino acid sequences (181 amino acids) of the ver-1 homologs had at most two amino acid changes relative to A. parasiticus SYS-4 ver-1. Transcripts of ver-1 homologs in the strains of A. oryzae and A. sojae examined were not detected by the polymerase chain reaction coupled with reverse transcription. By Southern analysis, a total of 46 strains of A. oryzae were examined for the presence of the ver-1 homolog. The homolog was detected in 38 strains, but not in 8 strains. Morphologically, strains with and without the ver-1 homolog were indistinguishable. Thus, A. oryzae contains strains with and without a homolog of the aflatoxin biosynthetic gene ver-1.
Aflatoxins↗
Pharmacokinetic disposition and arthropathic potential of oral ofloxacin in dogs.
We examined the relation between the pharmacokinetic disposition and arthropathic potential of ofloxacin, a new quinolone antibacterial agent, using both male immature (3-month-old) and mature (18-month-old) beagles. Ofloxacin was orally administered to these dogs at 20 mg/kg once daily for 8 consecutive days, and the animals were killed 2 h after the last treatment. Serum ofloxacin concentrations were repeatedly measured on days 1 and 7 by use of high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were calculated. In addition, on day 8, the drug concentrations in the joint synovial fluid and humeral and femoral condyles were measured. Clinico-pathological tests of blood and serum or histopathological examination of bone specimens were also performed. Arthropathy was macroscopically observed in the cartilage surface of all immature dogs, but not in mature dogs. There were, however, no noticeable differences in pharmacokinetic parameters between the two age groups of dogs or between single and 7-day treatments. In contrast to the occurrence of arthropathic lesions, the synovial fluid and condylar drug concentrations in immature dogs was equal to or lower than those in mature dogs, suggesting that the pharmacokinetic disposition of ofloxacin may not be essential for cartilage lesions.
Administration, Oral↗
Pharmacologic preconditioning induced by beta-adrenergic stimulation is mediated by activation of protein kinase C.
Ischemic preconditioning (I-PC) occurs via activation of protein kinase C (PKC). This study was undertaken to determine whether pharmacologic preconditioning by beta-adrenergic stimulation (beta-PC) is mediated by PKC activation. Isolated rat hearts were subjected to 40-min ischemia and 30-min reperfusion. Beta-PC was induced by 0.25 microM isoproterenol pretreatment for 2 min followed by 10-min normoxic perfusion. Beta-PC enhanced the recovery of rate-pressure product of the ischemic/reperfused heart (79.1 +/- 8.4% vs. 12.4 +/- 1.6% of initial for Non-PC group, n = 6) and attenuated the release of creatine kinase during 30-min reperfusion (30.2 +/- 2.2 vs. 59.8 +/- 6.1 nmol/min/g wet wt for Non-PC group, n = 6), similar to an I-PC stimulus of 5-min ischemia and 5-min reperfusion. Treatment with 50 microM polymyxin B, a PKC inhibitor, abolished the cardioprotection of both beta-PC and I-PC. Furthermore, similar changes in subcellular distribution of PKC were induced by both beta-PC and I-PC. The changes in subcellular distribution of PKC-delta suggested its translocation from cytosol to membrane fraction, a marker of PKC activation. These results suggest that the cardioprotection induced by beta-PC, like I-PC, is mediated by PKC activation.
Adrenergic beta-Agonists↗
Application of hepatic tolerance tests to the functional reserve assessment in rat models of fatty liver.
The present study was designed to define whether maximal removal rate of indocyanine green (ICG Rmax), plasma cyclic 3',5'-adenosine monophosphate (cAMP) response to exogenous glucagon (peak to basal ratio of cAMP level: P/B cAMP) and plasma half-life of galactose (t1/2 galactose) can measure the hepatic functional reserve of fatty liver prepared in rats fed choline-deficient (9 weeks), 2% cholesterol (2 weeks) or 0.25% DL-ethionine (2 weeks) diet. Although changes in cholesterol and phospholipid values in serum during feeding periods differed among the models, histopathologic examinations in the liver of almost all animals revealed intermediate to severe fatty liver with or without fibrosis at each termination. ICG Rmax and P/B cAMP were significantly decreased in rats fed choline-deficient or DL-ethionine diet, implying reductions in hepatic functional mass and disturbances in hepatic cAMP production. Meanwhile, t1/2 galactose showed no change in any of the models, suggesting that glucose metabolisms in the models used may be preserved. These findings demonstrate that ICG Rmax and P/B cAMP can apply to measurement of hepatic surviving reserve of fatty liver with fibrosis.
Animals↗
[Adjuvant chemotherapy with UFT or UFT with OK-432 to patients with gastric and colorectal cancer. Kanto Adjuvant Study Group].
In Japan, long-term oral therapy with tegafur in combination with immunopotentiators is commonly used as adjuvant therapy after curative resection of gastric or colorectal can for gastric and colorectal cancer. When the outcome was analyzed in terms of the relative performance (R.P.) and the individual dose intensity (I.D.I.) of OK-432, gastric cancer patients with a R.P. of 0.5 or higher tended to have a better survival curve. There were no marked differences in lymphocytes subsets, except that the Leu 7 level at 3 months after gastric cancer resection was significantly higher (p < 0.05) in group B than in group A. Thus, no inhibition of the anticancer effect of UFT was noted during long term combination therapy with UFT and an immunopotentiator as postoperative adjuvant therapy for patients who underwent curative resection of gastric or colorectal cancer. The results suggest that UFT combined with long-term OK-432 maintenance therapy may contribute to improve survival rates in gastric cancer patients.
Adjuvants, Immunologic↗
Effects of long-term treatment with eicosapentaenoic acid on the heart subjected to ischemia/reperfusion and hypoxia/reoxygenation in rats.
The effects of eicosapentaenoic acid (EPA) and long-term treatment with EPA-ethylester (EPA-E) were examined in perfused rat hearts subjected to ischemia/reperfusion and adult rat cardiomyocytes subjected to hypoxia/reoxygenation. EPA (0.1 microM) improved postischemic contractile dysfunction of the ischemic/reperfused heart. EPA (10 microM) attenuated hypoxia/reoxygenation-induced morphological deterioration of cardiomyocytes. The results suggest the presence of direct cardioprotective effects of EPA. Rats were orally treated for 4 weeks with 1 g/kg/day of EPA-E to elucidate ex vivo effects of EPA, and the fatty acid composition of cardiac phospholipids was determined. The percent ratio of EPA in total fatty acids of cardiac phospholipids increased whereas that of arachidonic acid decreased. The percent ratio of n-3/n-6 fatty acid did not increase. Treatment with EPA-E did not improve the post-ischemic contractile function, but attenuated the ischemia/reperfusion-induced release of prostaglandins during reperfusion. Treatment with EPA-E preserved a better morphological appearance of the cardiomyocytes subjected to hypoxia/reoxygenation. The results suggest that the mechanisms responsible for cytoprotective effects of hypoxic/reoxygenated cardiomyocytes or inhibition of metabolic alterations of the ischemic/reperfused heart by long-term EPA-E treatment did not contribute substantially to recovery of post-ischemic contractile dysfunction. The direct in vitro effects of EPA may play a role in the protection of the heart from ischemia/reperfusion or hypoxia/reoxygenation injury.
Animals↗