Search PubMed⌕ Search

Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 379 records · Page 21Linked to original sources
PubMed1997

Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite: implications for the treatment of multiple sclerosis.

In this study we provide further evidence associating activated cells of the monocyte lineage with the lesions of multiple sclerosis (MS). Using a combination of immunohistochemistry and reverse transcriptase-dependent in situ polymerase chain reaction analysis, we have identified monocytes expressing inducible nitric oxide synthase (iNOS) to be prevalent in the plaque areas of post mortem brain tissue from patients with MS. In addition, we have obtained evidence of the nitration of tyrosine residues in brain areas local to accumulations of iNOS-positive cells. In parallel studies we have assessed the effects of inhibitors of iNOS induction, as well as scavengers of nitric oxide and peroxynitrite in the experimental allergic encephalomyelitis model. Significant therapeutic effects were seen with the inhibitor of iNOS induction, tricyclodecan-9-xyl-xanthogenate, a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, and a peroxynitrite scavenger, uric acid. In particular, treatment with high doses of uric acid virtually prevented clinical symptoms of the disease. Together with our demonstration of the presence of activated macrophages expressing high levels of iNOS and evidence of peroxynitrite formation in brain tissue from patients with MS, these findings are of importance in the development of approaches to treat this disease.

Animals↗
PubMed1997

Superoxide scavenging activity of erythromycin-iron complex.

We evaluated superoxide (O2-.) scavenging activity of erythromycin (EM) and of EM-iron complex by means of electron spin resonance spectroscopy, luminol-dependent chemiluminescence assay, and cytochrome c reduction assay. The EM-iron complex was produced by mixing EM with equal molar iron chloride and was stable in neutral buffer. The EM-iron complex reduced the amount of O2-. produced by xanthine oxidase/hypoxanthine without inhibiting the enzyme activity. It also reduced the amount of O2-. release from phorbor ester-stimulated human neutrophils and alveolar macrophages. EM alone showed few such effects. The scavenging activity of the complex was equal to that of L-ascorbic acid. These results in vitro suggest a possibility that the O2-.-scavenging effect of EM-iron complex contributes to the anti-inflammatory action of EM used in treating chronic inflammatory lung disease independent of its antimicrobial activity.

Erythromycin↗
PubMed1997

Activation of human matrix metalloproteinases by various bacterial proteinases.

Matrix metalloproteinases (MMPs) are zinc-containing proteinases that participate in tissue remodeling under physiological and pathological conditions. To test the involvement of bacterial proteinases in tissue injury during bacterial infections, we investigated the activation potential of various bacterial proteinases against precursors of MMPs (proMMPs) purified from human neutrophils (proMMP-8 and -9) and from human fibrosarcoma cells (proMMP-1). Each proMMP was subjected to treatment with a series of bacterial proteinases at molar ratios of 0.01-0.1 (bacterial proteinase to proMMP), and activities of MMPs generated were determined. Among six different bacterial proteinases, thermolysin family enzymes (family M4) such as Pseudomonas aeruginosa elastase, Vibrio cholerae proteinase, and thermolysin strongly activated all three proMMPs via limited proteolysis to generate active forms of the MMPs. N-terminal sequence analysis of the active MMPs revealed that cleavage occurred at the Val82-Leu83 and Thr90-Phe91 bonds of proMMP-1 and proMMP-9, respectively, which are located near the N terminus of the catalytic domain of MMPs. In contrast, Serratia 56-kDa proteinase and Pseudomonas alkaline proteinase, both of which are classified as members of the serralysin subfamily of zinc metalloproteinases (family M10), and Serratia 73-kDa thiol proteinase did not evidence proteolytic processing or activation of proMMP-1, -8, and -9 under these experimental conditions. These results indicate that bacterial proteinases may play an important role in tissue destruction and disintegration of extracellular matrix at the site of infections.

Amino Acid Sequence↗
PubMed1997

Localization of 16 exons to a 450-kb region involved in the autoimmune polyglandular disease type I (APECED) on human chromosome 21q22.3.

As a step toward identifying the pathogenic genes for autoimmune polyglandular disease type I (APECED) and other disorders mapped to the PFKL locus on chromosome 21q22.3, we have constructed a cosmid/BAC (bacterial artificial chromosome) contig of 450 kb covering markers D21S1460-D21S25-PFKL-D21S154 and performed exon trapping. We isolated 22 distinct exons including 6 exons derived from two known genes (PFKL and EHOC-1). Among 16 novel exons, 2 exons matched with human expressed sequence tags (EST) and 7 exons showed homology at predicted amino acid sequence level with proteins from other species. These 16 exons were mapped back to the cosmid contigs, 12 of which were confirmed for their expression by polymerase chain reaction (PCR) screening of human cDNA libraries of various tissues. These exon sequences and a transcript map will aid for isolation of corresponding genes which will be identified as candidate genes involved in the pathogenesis of disorders mapped to the 21q22.3 region.

Amino Acid Sequence↗
PubMed1997

Effect of a protein phosphatase inhibitor, okadaic acid, on thrombomodulin expression in cultured human umbilical vein endothelial cells.

We examined the effects of okadaic acid, a potent specific inhibitor of protein phosphatases 1 and 2A, on the expression of thrombomodulin (TM), a cell surface anti-thrombotic glycoprotein, on cultured human umbilical endothelial cells. Okadaic acid (2.5-10 nM) significantly increased TM antigen levels in parallel with its cofactor activity for thrombin-dependent protein C activation. Incubation of cells with 10 nM okadaic acid for 18 h induced an approximately 240% up-regulation of TM antigen levels that was accompanied by an increase in TM mRNA levels. Co-incubation of cells with okadaic acid and dibutyryl cyclic AMP further increased TM antigen levels. Furthermore, the effect of cAMP on TM expression was augmented by the pretreatment of cells with 10 nM okadaic acid for 18 h. These results provide evidence for the involvement of protein phosphatase in the cellular regulatory mechanisms for TM expression, which is distinct from that by cAMP.

Blotting, Northern↗
PubMed1997

Quantitative analysis of scatter- and attenuation-compensated dynamic single-photon emission tomography for functional hepatic imaging with a receptor-binding radiopharmaceutical.

A new method for quantitative liver study was developed using the tracer technetium-99m diethylene triamine penta-acetic acid-galactosyl human serum albumin (99mTc-GSA), an analog ligand of the asialoglycoprotein receptor, which is a hepatocyte surface receptor specific for galactose-terminated glycoproteins. For quantitative dynamic single-photon emission tomographic (SPET) studies, attenuation compensation using transmission computed tomography (TCT) and the triple energy window (TEW) scatter compensation method were evaluated. As the TCT source, we used an uncollimated multi-tube source with the TEW scatter compensation method. To verify the accuracy of cross-calibrated SPET values as compared with measured radioactivities, we performed SPET of a cylindrical water pool phantom which contains seven hot rods filled with different concentrations of 99mTc activities, simulating the scan conditions in human studies. The results of the phantom studies showed good linearity and accuracy of the SPET values, with R2=0.993 and a regression line of y=0.941x+5.48. From the analysis of a kinetic model based on a one-compartment model, focussing on the initial stage of several minutes after 99mTc-GSA injection and taking the physiological expression presented in a three-compartment analysis into account, we introduced the Rutland equation (Patlak plot) in the 99mTc-GSA study by which the overall and regional effective hepatic blood flow (EHBF) and hepatic blood pool volume were determined. Preliminary clinical evaluations were performed for four normal male subjects (23-35 years of age) and one patient. Forty sequential 30-s dynamic SPET acquisitions were obtained for a period of 20 min following the intravenous injection of 99mTc-GSA with venous blood sampling at 10 min. After scatter compensation, the SPET images were reconstructed with attenuation compensation using an attenuation map obtained from TCT. The average normal value for the total EHBF was 468+/-83 ml/min and that for the hepatic blood pool volume, 777+/-123 ml. Functional images of the distribution of regional values of EHBF (ml/min/voxel) and hepatic blood pool volume (ml/voxel) were also generated corresponding to the original SPET images. The EHBF images showed regional liver function, higher in the right lobe than the left lobe in the normal cases, and the heptic blood pool volume images showed the distribution of intensified high values along major vascular structures. Receptor imaging with 99mTc-GSA using the Rutland method and dynamic SPET with scatter and attenuation compensation is an effective technique that allows the evaluation of total and regional hepatic functional parameters (EHBF, hepatic blood pool) in vivo.

Adult↗
PubMed1997

Halothane inhibition of acetylcholine-induced relaxation in rat mesenteric artery and aorta.

PURPOSE: The effect of halothane was compared on acetylcholine (ACh)-induced relaxation of the mesenteric artery and the aorta in rats. METHODS: The responses of isolated rat aortic and mesenteric arterial ring segments precontracted with phenylephrine to ACh (10(-8)-10(-5) M), in the presence of halothane 0-3%, were compared using isometric force tension recordings. Effects of NG-nitro-l-arginine (L-NOARG, 3 x 10(-5), methylene blue (MB, 5 x 10(-6) M), oxyhaemoglobin in (OxyHB, 10(-7) M), and various potassium channel inhibitors; tetraethylammonium (TEA, 10(-5) M, 10(-3) M), apamin (AP, 10(-7) M), charybdotoxin (ChTx, 10(-7) M) and glibenclamide (GC, 10(-5) M) on ACh-induced relaxation in mesenteric artery were tested. Using radioimmunoassay, ACh (10(-6) M)-induced guanosine 3':5'-cyclic monophosphate (cGMP) accumulation of mesenteric arterial rings pretreated with L-NAORG were also measured. RESULTS: L-NOARG partially inhibited ACh-induced relaxation in mesenteric arterial rings (P < 0.05, maximum relaxation reduced by approximately 50%), whereas it abolished them in aortic rings. The remaining relaxation resistant to L-NOARG in mesenteric arterial rings was insensitive to additional MB or OxyHB, and was not accompanied by increases in cGMP contents of rings. Halothane inhibited endothelium-dependent relaxation in aorta and mesenteric arterial rings. This inhibitory effect was larger in aorta. Halothane also inhibited NO independent EDHF-dependent relaxation in the mesenteric arterial rings, CONCLUSION: Despite a similar inhibitory effect on the EDHF relaxing pathway, halothane has a larger effect on endothelium-dependent relaxation in the aorta (NO dependent mainly) than in the mesenteric rings (NO and EDHF dependent).

Acetylcholine↗
PubMed1997

Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T1-weighted images and elemental concentrations in brain.

In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 +/- 0.38, 2.12 +/- 0.37, and 1.38 +/- 0.24 (micrograms/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50% more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus.. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus.

Basal Ganglia↗
PubMed1997

Prostate specific antigen adjusted for the transition zone volume as an indicator of prostate cancer.

PURPOSE: We compared prostate specific antigen (PSA) adjusted for the transition zone volume with PSA and PSA density with regard to value in diagnosing prostate cancer in men with intermediate PSA levels of 4.1 to 10.0 ng./ml. in a community based urology practice. MATERIALS AND METHODS: Between October 1994 and May 1996, PSA transition zone was obtained from 92 of 94 men who underwent systematic sextant biopsies and had a PSA value between 4.1 and 10.0 ng./ml. PSA transition zone, calculated by dividing the PSA value by the volume of the transition zone of the prostate, was compared with PSA and PSA density via the receiver operating characteristic (ROC) curves. RESULTS: Of the 92 men 12 (13.0%) had prostate cancer. ROC curve analysis demonstrated that PSA transition zone and PSA density predicted the biopsy outcome significantly better than PSA (p <0.05 and p <0.01, respectively). In a subset of 59 men with normal digital rectal examination PSA transition zone predicted the biopsy outcome better than PSA density, although without significant difference. With a cutoff value of 0.3 PSA transition zone had a sensitivity of 75% and a specificity of 54%. CONCLUSIONS: PSA transition zone is more specific than PSA in distinguishing benign from malignant disease in men with intermediate PSA levels of 4.1 to 10.0 ng./ml., especially in those with normal digital rectal examination. Further study is necessary to discuss whether PSA transition zone is superior to PSA density.

Aged↗
PubMed1997

Potential antidepressant properties of forskolin and a novel water-soluble forskolin (NKH477) in the forced swimming test.

The mechanisms of the antidepressant activity of forskolin and a novel water soluble forskolin analog (NKH477) were studied using the forced swimming method in rats. Forskolin (0.01-0.1 mg/kg) and NKH477 (0.01-0.1 mg/kg) dose-dependently decreased ratings of immobility, with effects similar to those of amitriptyline treatment. The maximum effects of forskolin and NKH477 were observed at 0.01 mg/kg dose which is 150 more times potent than that (15 mg/kg) of amitriptyline. At a high dose (1.0 mg/kg) of forskolin and NKH477, the duration of immobility was returned to control levels. Forskolin and NKH477 did not influence the spontaneous locomotor activity at intraperitoneal injection doses from 0.01 to 1 mg/kg. Furthermore chronic administration with NKH477 at oral dose from 0.5 to 1.5 mg/kg significantly decreases the duration of immobility. These data indicate that both forskolin and NKH477 have strong antidepressive potency, consistent with the hypothesis that elevation of the cAMP cascade system may have an important role in antidepressive effects.

Administration, Oral↗
PubMed1997

Generation of anaphylatoxins through proteolytic processing of C3 and C5 by house dust mite protease.

BACKGROUND: The group 3 allergen of Dermatophagoides species (Der p 3 and Der f 3) has been identified as a 30 kd trypsin-like protease of the house dust mite. We previously showed that the 30 kd protease from Dermatophagoides farinae (Df-protease) could activate the bradykinin-generating cascade and exacerbate inflammatory reactions. OBJECTIVE: The purpose of this study was to determine whether Df-protease could enzymatically generate anaphylatoxins from complement components C3 and C5. METHODS: Df-protease was incubated with human serum C3 or C5 in a purified system, and the anaphylatoxin activity produced was assayed by measuring enhancement of vascular permeability and release of histamine from mast cells triggered by C3a and by assessing chemotaxis of polymorphonuclear cells caused by C5a. We also attempted to determine whether protease isolated from house dust could cause release of C5a from C5. RESULTS: Df-protease showed strong activation of C3 and C5, producing C3a and C5a by proteolytic cleavage of the complements. An appreciable amount of Df-protease was recovered in the house dust extract, and the house dust protease caused C5a release from C5. CONCLUSION: Df-protease activated the complement system to produce anaphylatoxins. Thus it is suggested that house dust mite proteases may contribute to the pathogenesis of allergic and inflammatory diseases caused by house dust allergens.

Air Pollution, Indoor↗
PubMed1997

Changes in cellular composition induced by neocarzinostatin pretreatment in Meth A-bearing mice and the responsible antitumor effector cells.

We previously reported that tumor eradication was induced by a single injection of neocarzinostatin (NCS) between 1 day and 4 weeks before Meth A transplantation in Balb/c mice via augmenting host-mediated antitumor activity. In order to elucidate the mechanism of this tumor eradication, the cellular components of spleen and regional lymph nodes, tumor infiltrating cells and antitumor effector cells were investigated. Pretreatment with NCS on day -3 caused an increase in the percentage of T-cell subsets, a decrease in the percentage of B-cells, Mac-1+ cells and asialo GM1+ cells and a decrease of the total cell number in the spleen. These changes were observed before but not during the period of tumor regression and were also observed in non-transplanted mice with NCS treatment. In the lymph nodes, while B-cells increased on Meth A transplantation, this was suppressed by NCS pretreatment. Although histological examination of tumor nodules showed the presence of only a few host immune cells in the tumor tissue, the area of necrosis was already extensive on day 7 and expanded thereafter. In vivo depletion of whole T-cells, T-cell subsets or asialo GM1+ cells by antibody treatment suggests that the antitumor effector cells in tumor eradication were Thy1,2+/Lyt2+, and at least some of which also express asialo GM1 antigen and that L3T4+ T-cells were also involved in tumor eradication.

Animals↗
PubMed1997

The well-balanced nucleoside-nucleotide mixture "OG-VI" for special medical purposes.

Nucleotides and nucleosides are essential components in all cells. However, nucleotides have not been supplied in parenteral nutrition regimens. We developed a well-balanced nucleoside-nucleotide mixture "OG-VI" and examined its effect in animals under some stressed conditions. OG-VI was composed of 30 mmol/l of inosine, 30 mmol/l of guanosine monophosphate, 30 mmol/l of cytidine, 22.5 mmol/l of uridine and 7.4 mmol/l of thymidine. The whole body protein turnover increased significantly in rats receiving total parenteral nutrition (TPN) with OG-VI solution after 70% hepatectomy, compared with rats receiving normal TPN without OG-VI (122.1 +/- 20.9 mgN.kg-1.h-1 vs. 97.4 +/- 10.1 mgN.kg-1.h-1, P < 0.01, n = 10). OG-VI significantly enhanced protein synthesis while it did not decrease protein breakdown. The effect of OG-VI on myocardium after hypoxic challenge was also examined in rats. The creatine phosphate (PCr)/inorganic phosphate (Pi) was decreased in normal rat myocardium after hypoxic challenge. However, in the rats administered OG-VI, PCr/Pi was maintained at baseline level and did not decrease after hypoxia. There was no significant change in the level of adenosine triphosphate (ATP) between before and after hypoxic challenge in myocardium of the rats administered OG-VI. In the rats receiving normal saline, instead of OG-VI, the ATP level decreased significantly after hypoxic challenge (4132 +/- 276 nmol/g tissue, n = 3, vs. 3439 +/- 465 nmol/g tissue, n = 5, P < 0.05). These data suggested that the well-balanced nucleoside-nucleotide mixture, OG-VI improved nitrogen metabolism and might stimulate synthesis of high-energy phosphate in recovery after severe surgical stress.

Animals↗
PubMed1997

Dissociation of bone formation markers in bone metastasis of prostate cancer.

To clarify the meaning and clinical value of bone formation markers in bone metastasis from prostate cancer, we investigated the bone formation markers carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BA1-p) and osteocalcin, so-called bone gla protein (BGP) in 43 prostate cancer patients with and 46 patients without overt bone metastasis. Patients with bone metastasis were evaluated repeatedly by bone scan at intervals of 3-6 months. The expression patterns of bone formation markers in patients with progression of bone metastasis became dissociated; BA1-p and PICP were elevated in patients with progression of bone metastasis but BGP was not. Instead, BGP showed slight elevation in patients with improvement and complete remission of bone metastasis. PICP, BA1-p and BGP are all bone formation markers, but each marker appears in a different phase of bone formation: PICP appears in proliferation phase, BA1-p appears in matrix maturation phase and BGP appears in late bone formation phase. Our findings that BGP was not elevated in progression of bone metastasis and that it increased slightly with improvement and complete remission of bone metastasis may imply that the bone formation that occurs in blastic bone metastasis is different from normal bone formation.

Aged↗
PubMed1997

Inhibition of [3H]MK-801 binding by ferrous (II) but not ferric (III) ions in a manner different from that by sodium nitroprusside (II) in rat brain synaptic membranes.

The addition of sodium nitroprusside (SNP) significantly inhibited binding of (+)-5- [3H]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) to an ion channel associated with the N-methyl-D-aspartate (NMDA) receptor in a concentration-dependent manner at concentrations of >1 microM in rat brain synaptic membranes not extensively washed. However, neither S-nitroso-N-acetylpenicillamine nor S-nitroso-L-glutathione inhibited binding even at 100 microM. Of the two compounds structurally related to SNP (II), similarly potent inhibition was induced by potassium ferrocyanide (II) but not by potassium ferricyanide (III). In addition, ferrous chloride (II) induced much more potent inhibition of binding than ferric chloride (III), at a similar concentration range. In contrast, iron chelators prevented the inhibition by ferrous chloride (II) without markedly affecting that by SNP (II) and potassium ferrocyanide (II). Pretreatment with ferrous chloride (II) also led to potent inhibition of [3H]MK-801 binding in a manner insensitive to subsequent addition of the iron chelators. Pretreatment with Triton X-100 resulted in significant potentiation of the ability of ferrous chloride (II) to inhibit [3H]MK-801 binding irrespective of the addition of agonists, moreover, although binding of other radioligands to the non-NMDA receptors was unaltered after pretreatment first with Triton X-100 and then with ferrous chloride (II). These results suggest that ferrous ions (II) may interfere selectively with opening processes of the NMDA channel through mechanisms entirely different from those underlying the inhibition by both SNP (II) and potassium ferrocyanide (II) in rat brain.

Animals↗
PubMed1997

Decrease of N-acetylaspartate after ACTH therapy in patients with infantile spasms.

Apparent brain atrophy has been frequently observed at CT and MRI after ACTH therapy in patients with infantile spasms. There are several hypotheses to explain ACTH-induced brain shrinkage: 1) a catabolic effect of ACTH on brain tissue, 2) a mineralocorticoid effect resulting in a loss of water and 3) an increase in cerebrospinal fluid (CSF) pressure compressing the brain. An average of 0.21 +/- 0.03 mg/kg of ACTH was administered to nine patients over a period of 14 to 17 days. Water content and concentrations of N-acetylaspartate (NAA), creatine and phosphocreatine (Cr + PCr), and choline (Cho) were measured before, immediately after, and several months after the ACTH therapy by using in-vivo 1H magnetic resonance spectroscopy (MRS). Only NAA concentration exhibited a significant change during the study (6.6 +/- 1.5 mmol/kg, 5.4 +/- 1.1, and 7.0 +/- 1.5, p = 0.017). There was no significant change in Cr + PCr, in Cho, or in water content. These data suggest catabolic effects of ACTH on brain tissue, such as cell loss, decrease in NAA synthesis in mitochondria, and leakage of NAA from cell membrane.

Adrenocorticotropic Hormone↗