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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 451 records · Page 25Linked to original sources
PubMed1996

Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals.

The role of nitric oxide (NO) in the pathogenesis of influenza virus-induced pneumonia in mice was investigated. Experimental influenza virus pneumonia was produced with influenza virus A/Kumamoto/Y5/67(H2N2). Both the enzyme activity of NO synthase (NOS) and mRNA expression of the inducible NOS were greatly increased in the mouse lungs; increases were mediated by interferon gamma. Excessive production of NO in the virus-infected lung was studied further by using electron spin resonance (ESR) spectroscopy. In vivo spin trapping with dithiocarbamate-iron complexes indicated that a significant amount of NO was generated in the virus-infected lung. Furthermore, an NO-hemoglobin ESR signal appeared in the virus-infected lung, and formation of NO-hemoglobin was significantly increased by treatment with superoxide dismutase and was inhibited by N(omega)-monomethyl-L-arginine (L-NMMA) administration. Immunohistochemistry with a specific anti-nitrotyrosine antibody showed intense staining of alveolar phagocytic cells such as macrophages and neutrophils and of intraalveolar exudate in the virus-infected lung. These results strongly suggest formation of peroxynitrite in the lung through the reaction of NO with O2-, which is generated by alveolar phagocytic cells and xanthine oxidase. In addition, administration of L-NMMA resulted in significant improvement in the survival rate of virus-infected mice without appreciable suppression of their antiviral defenses. On the basis of these data, we conclude that NO together with O2- which forms more reactive peroxynitrite may be the most important pathogenic factors in influenza virus-induced pneumonia in mice.

Animals↗
PubMed1996

TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice.

In previous reports, we showed that tumor-derived TGF-beta induced overproduction of IL-10, and these suppressive cytokines caused macrophage suppression in EL4-bearing mice. Proliferation of T cells from EL-4, but not IL-2, whereas T cells from normal mice were responsive to IL-2. A balance between Th1- and Th2-type cytokine production in EL4-T in response to anti-CD3 Ab or phorbor myristate acetate plus A23187 shifted toward the Th2 dominant pattern. The prevention of TGF-beta and IL-10 activates in vivo by administration of anti-IL-10 Ab (anti-IL-10) or anti TGF-beta Ab (anti-TGF-beta) resulted in the reduction in EL4-T of both IL-4 dependent proliferation and Th2-dominant cytokine production induced by anti-CD-3 stimulation. In addition, the anti-TGF-beta treatment resulted in complete restoration in EL4-T of suppressed IL-2 responsiveness, IL-2R expression, and Th1-type cytokine production, whereas the anti-IL-10 treatment produced partial recovery. These results lead us to conclude that TGF-beta drives the shift in the Th1/Th2 balance toward Th2 via IL-10-mediated development of the Th2 responses and via inhibition of the Th1-type responses directly in EL4-bearing mice.

Animals↗
PubMed1996

Renal cell carcinoma in a patient with Beckwith-Wiedemann syndrome.

We report the case of a patient with Beckwith-Wiedemann syndrome (BWS) who developed renal cell carcinoma (RCC). At birth, this patient presented with macroglossia, diastasis recti, mild gigantism, hepatomegaly and hypoglycemia, and the diagnosis of BWS was made. At 22 months, an intrapelvic rhabdomyosarcoma was detected and resected. At 37 months, computed tomography (CT) demonstrated a small mass with high attenuation in the right kidney, which was surgically confirmed to be RCC.

Beckwith-Wiedemann Syndrome↗
PubMed1996

Telomere shortening in peripheral blood cells was related with aging but not with white blood cell count.

Telomeres in somatic cells are progressively shortened with aging. We investigated the relationship between the telomere length and other factors which may affect the frequency of cell divisions, in peripheral blood cells. Shortening of telomeric repeats was correlated with aging (p < 0.0001), but not with white blood cell count, neutrophil count, and smoking habit. Not only the number of cell divisions, but also some other factors, such as upregulation level of telomerase activity concomitant with the cell division in hematopoietic progenitor cells, might affect the length of telomeric repeats in blood cells.

Adult↗
PubMed1996

Primary sclerosing cholangitis associated with increased peripheral eosinophils and serum IgE.

Symptoms of cholestasis, including epigastralgia, fever, and jaundice, with marked increases in peripheral eosinophils and serum IgE in a 20-year-old man are reported here. Endoscopic retrograde cholangio-pancreatography (ERCP) detected constrictions of the bile ducts, compatible with primary sclerosing cholangitis (PSC). The symptoms and blood parameters of liver dysfunction were associated with the degree of eosinophilia and high serum IgE levels. During corticosteroid therapy, all of these parameters improved, and morphologic improvements of the bile ducts were also observed. The pathogenesis of PSC may be explained, in part, by the concept of hypereosinophilic syndrome or allergic reaction.

Adult↗
PubMed1996

The detection of picoplankton 16S rDNA in cases of drowning.

Picoplankton belonging to the Synechococcus genus in cyanobacteria (approximately 1 micron in size) are found ubiquitously in Lake Biwa, Japan. However, they could not be morphologically discriminated from other bacteria by microscopy. In this study we attempted to use picoplankton for the diagnosis of drowning by PCR analysis of the 16S ribosomal DNA (rDNA). We designed primers complementary to the variable regions of 16S rDNA of the picoplankton we had sequenced. A comparison was made of the PCR products from the three picoplanktons, five other cyanobacteria, Melosira (diatom), Staurdstrum (green alga), bacteria from Lake Baikal, and humans. The picogram order of template DNA from picoplankton was specifically amplified by the primers. When the template of picoplankton was mixed with human lung tissue, at least 10 ng of template DNA was needed to obtain a PCR product. The isolation of the picoplankton from human lung tissue increased the sensitivity of PCR more than a hundred-fold. The specific PCR products of the picoplankton were obtained from formalin-fixed drowning tissue. Molecular biological diagnosis of drowning was successful using picoplankton 16S rDNA.

Animals↗
PubMed1996

Hereditary cerebellar ataxia with Leber's hereditary optic neuropathy mitochondrial DNA 11778 mutation.

We investigated a family with optic atrophy which occurred in childhood or early adulthood plus late-onset cerebellar ataxia. The magnetic resonance imaging in the proband revealed cerebellar atrophy. The proband and her brother were homoplasmic for the most common mitochondrial DNA (mtDNA) 11778 mutation associated with Leber's hereditary optic neuropathy (LHON). This study showed further evidence that central nervous system lesions can occur in cases of LHON mtDNA mutation.

Adult↗
PubMed1996

Long-term patterns of change in ERPs across repeated measurements.

Ten subjects were tested for eight sessions using an auditory oddball paradigm at 1-week and 1-month intervals to examine the stability of multiple event-related potential (ERP) components, in terms of trait (between session) and state (within session) reliability. The between session reliabilities presented as intraclass correlations (r') were 0.54 for the P300 amplitude and 0.47 for the P300 latency. Pearson correlation coefficients, representing within-session reliabilities, ranged from 0.54 to 0.68 for P300 amplitude and 0.12 to 0.46 for P300 latency. Statistical analysis of results from the eight sessions demonstrated that session-dependent reduction and recovery of the P300 amplitude occurred during the testing sessions. Other ERPs measurements such as N100-P300, N200-P300, N100, and N200 amplitudes did not exhibit any significant changes. The between- and within-session reliabilities of P300 components suggest that P300 may be a reproducible biological marker of state and trait even across repeated measurements. We speculate that the observed long-term patterns of change in P300 may have reflected habituation and dishabituation of certain processes in the human central nervous system.

Adult↗
PubMed1996

Bradykinin and nitric oxide in infectious disease and cancer.

Vascular pathophysiology at the sites of bacterial infection and cancerous tissues share numerous common events similar to inflammatory tissue. Among them enhanced vascular permeability is the universal and hallmark event mediated by bradykinin. All 16 or more bacterial or fungal proteases we have examined activated one or more steps of the kinin generating Hageman-factor-kallikrein cascade. In the meantime, most of the microbial proteases rapidly inactivated various plasma inhibitors such as alpha 1-protease inhibitor and alpha 2-macroglobulin. In addition to the extracellular proteases, bacterial cell wall components (negatively charged LPS) of gram-negative bacteria and teichoic acid moieties of gram-positive bacteria activate the Hageman-factor-kallikrein system and exert hypotensive effects via kinin generation. Endotoxin (LPS) also induces nitric oxide synthase (NOS) which appears to exhibit a rather slow, but significant, effect in relaxing the vascular tone of the infected animal (thus hypotension). Furthermore, bacterial proteases can activate the matrix metalloproteinase (collagenase) resulting in exacerbation of tissue injury in the diseased animal. Many tumor cells or tissues excrete plasminogen activator, and hence activate plasminogen. The plasmin thus generated activates procollagenases, as well as the Hageman-factor-kallikrein system, resulting in pronounced extravasation. Fluid accumulation in pleural and ascitic carcinomatoses is largely due to the activated bradykinin-generating system. We can also demonstrate and control enhanced vascular permeability using kallikrein inhibitors, especially the polymer-conjugated soybean trypsin inhibitor which exhibits a prolonged plasma t1/2, kinin antagonists, NOS inhibitors, NO scavengers, inhibitors of prostaglandins and others. Bacterial proteases induce shock in mice which can be prevented by the soybean trypsin inhibitor by blocking the kallikrein-kinin cascade. Therapeutic use of kinin antagonists and a kallikrein inhibitor has been made for infectious diseases such as septicemia and in tumor pathology.

Animals↗
PubMed1996

Further evidence of bradykinin involvement in septic shock: reduction of kinin production in vivo and improved survival in rats by use of polymer tailored SBTI with longer t1/2.

Involvement of bradykinin in septic shock and its therapeutic endeavor using soybean trypsin inhibitor (SBTI, Kunitz type) were investigated in an in vivo model of septic shock induced by pseudomonal elastase. Pseudomonal elastase injection at 0.5 mg/kg i.v. to guinea pigs resulted in elevation level of bradykinin in the blood from < 1 ng/ml to 25 ng/ml which was accompanied by a drop of mean arterial blood pressure (MABP) (about 45 mmHg). When native soybean trypsin inhibitor (SBTI, Kunitz type, 20 kDa) was injected, into this model, induction of bradykinin generation and hypotension by the bacterial protease treatment was completely obliterated as judged by the both levels of bradykinin and MABP. Specifically, by the treatment with SBTI, bradykinin levels did not increase and the drop of the blood pressure was minimal (< 10 mmHg) in this time frame (< 30 min). We designed and prepared succinylated gelatin-conjugated SBTI (suc-gel SBTI) with enlarged molecular mass (M(r) approximately 110,000) and higher area under the curve of the plasma concentration, which exhibits about 6 times longer plasma half-life (t1/2) and about 4 times larger area under the curve of plasma concentration. Suc-gel-SBTI suppressed the pseudomonal protease-induced shock much more effectively than native SBTI, the conjugate exhibited its effect for more than 3 h, while the native SBTI showed the effect only within 2 h after i.v. injection.

Animals↗
PubMed1996

An external reference for in vivo quantification of 1H spectroscopy.

We studied the validity of using an external signal reference for absolute quantification of brain metabolites. We chose cyclohexane as the signal standard. An expression of a perturbed magnetic field in diamagnetic cylindrical materials was first obtained by using a method of equivalent magnetic charges. Broadening of the spectrum in this perturbed magnetic field was then computed. We performed phantom studies. We measured the full width at half maximum (FWHM) of the cyclohexane and the signal ratio (SR) between water and cyclohexane in spheres of two different diameters, and in cylinders of various diameters and lengths. The observed FWHM and SR in the small cylinders had large variations in distribution, whereas those in the spheres and in the large cylinders had small variations. Specifically, in a cylinder with a diameter > 5 cm and with a length > 10 cm, the variation of the SR was < 1.0%. The diameter and the length of the cylinder preferably are large when a cylindrical material is adopted as an external signal standard.

Brain↗
PubMed1996

Biochemical properties of the monomeric mutant of human cathepsin E expressed in Chinese hamster ovary cells: comparison with dimeric forms of the natural and recombinant cathepsin E.

Cathepsin E (CE) is the only known aspartic proteinase that exists as a homodimer consisting of two fully catalytically active monomers, which are covalently bound by a disulfide bond between two cysteine residues at the NH2-terminal region (Cys43 in human pro-CE). To understand the physiological significance of the dimer formation, the monomeric mutant of human CE was constructed by site-directed mutagenesis (Cys43 ->Ser43) and expressed in Chinese hamster ovary (CHO) cells. Immunolocalization of the mutant protein at both the light and electron microscopic levels revealed the monomeric CE to be associated predominantly with the endoplasmic reticulum and the non-lysosomal endocytic organelles. The cellular localization of the monomeric protein was compatible with that of the wild-type (dimeric form) of recombinant human CE expressed in the same cells. The monomeric protein was generated primarily as the 46-kDa pro-CE with a high-mannose-type oligosaccharide chain in the cells. In addition to the maximal activation at around pH 3.5, a substantial proportion of the monomeric pro-CE was converted to the mature form by incubation at pH 7 and 37 degrees C for 5 min. In contrast, the dimeric pro-CE was scarcely activated by treatment at pH7. Although catalytic properties of the in vitro-activated monomeric CE appeared to be indistinguishable from those of the dimeric forms of natural and recombinant CE, the monomeric form was more unstable to pH and temperature changes than these dimeric forms. These results indicate that the dimerization of CE is not necessarily required for proper folding to express activity, correct intracellular localization and carbohydrate modification, but that it may be essential to structurally stabilize the molecule in vivo.

Amino Acid Sequence↗
PubMed1996

A beta-adrenoceptor agonist evokes a nitric oxide-cGMP relaxation mechanism modulated by adenylyl cyclase in rat aorta. Halothane does not inhibit this mechanism.

BACKGROUND: The objective of this study was to characterize the effects of halothane on the agonist-induced nitric oxide-cyclic GMP (NO-cGMP) mechanisms by comparing the intracellular signal transduction mediating isoproterenol- and acetylcholine-induced nitric oxide formation. METHODS: Isoproterenol-induced relaxations of rat aortic rings with and without endothelia were examined in the absence and presence of halothane. Studies were also done in the presence of inhibitors of nitric oxide-synthase, adenylyl cyclase, calmodulin, protein kinase A, and intracellular Ca2+ release mechanism. The relaxations under some of these conditions were compared with those induced by acetylcholine. Cyclic nucleotide contents of the rings were also measured. RESULTS: Isoproterenol relaxed aortic rings via the endothelium-dependent nitric oxide-cyclic GMP mechanism. Inhibition of adenylyl cyclase or of protein kinase A attenuated the isoproterenol-induced relaxations significantly but did not affect those induced by acetylcholine. Inhibition of intracellular Ca2+ release abolished the acetylcholine-induced relaxations but did not affect those induced by isoproterenol. Calmodulin inhibition attenuated both agonist-induced relaxations significantly. Unlike acetylcholine-induced relaxation, that induced by isoproterenol was not affected by halothane. Isoproterenol increased both the cyclic adenosine monophosphate and cGMP contents of rings significantly when endothelia were intact. Inhibition of nitric oxide synthase attenuated the isoproterenol-induced cGMP content increases significantly but did not affect the cyclic adenosine monophosphate content increases. Halothane (2%) did not affect isoproterenol-induced increases in nucleotide content. CONCLUSIONS: Isoproterenol-induced nitric oxide formation requires the activation of constitutive nitric oxide synthase, but the Ca2+ release mechanism is not involved in activating this enzyme. Halothane can inhibit the nitric oxide-cyclic GMP mechanism only when Ca2+ release is greatly involved in the activation of constitutive nitric oxide synthase.

Acetylcholine↗
PubMed1996

Bradykinin generation triggered by Pseudomonas proteases facilitates invasion of the systemic circulation by Pseudomonas aeruginosa.

To elucidate the mechanism of bacterial exoprotease in promotion of the intravascular dissemination of Pseudomonas aeruginosa, we examined the possible involvement of bradykinin (whose generation is induced by pseudomonal proteases in septic foci) in the invasion by bacteria, and in access of bacterial toxins to systemic blood circulation. P. aeruginosa 621 (PA 621), which produces very little protease, was injected intraperitoneally into mice together with pseudomonal exoproteases (elastase/alkaline protease). Dissemination of bacteria from the peritoneal septic foci to the blood was assessed by counting viable bacteria in the blood and spleen by use of the colony-forming assay. The results showed that pseudomonal proteases markedly enhanced (10- to 100-fold) intravascular dissemination of bacteria in mice. This enhancement was induced not only by pseudomonal proteases but also by bradykinin. More importantly, the increased spread of PA 621 induced by pseudomonal protease and bradykinin was significantly augmented by the addition of kininase inhibitors, indicating the direct involvement of bradykinin in bacterial dissemination. Similarly, bradykinin caused effective dissemination of pseudomonal toxins such as endotoxin (lipopolysaccharide) and exotoxin A when the toxins were injected into the peritoneal cavity with bradykinin. Furthermore, the lethality of the infection with PA 621 was strongly enhanced by pseudomonal proteases given i.p. simultaneously with PA 621. On the basis of these results, it is strongly suggested that pseudomonal proteases as well as bradykinin generated in infectious foci are involved in facilitation of bacterial dissemination in vivo.

Animals↗