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Biomedical subjects

T Mizuno

Publications and source records attributed to T Mizuno.

At least 307 records · Page 17Linked to original sources
PubMed1995

Role of endogenous endothelin in gastric mucosal injury induced by hemorrhagic shock in rats.

We examined the role of endogenous endothelin in the pathogenesis of hemorrhagic shock-induced gastric mucosal injury in rats. Animals were bled to induce hypotension (20-30 mm Hg) for 20 min and the shed blood was retransfused. Rats were sacrificed at the end of hypotension, 20 min, and 60 min after retransfusion, respectively. Gastric erosions were induced with this experimental protocol. The total area of erosions was minimal only at the end of hypotension, and increased time-dependently after blood retransfusion. Plasma endothelin concentration significantly increased at the end of hypotension and persistently increased after retransfusion, whereas in gastric endothelin concentration a significant increase was observed at 60 min after retransfusion. The gastric mucosal hemodynamics as assessed by continuous measurement with reflectance spectrophotometry showed ischemia associated with congestion after retransfusion. Treatment with a monoclonal antibody against endothelin (0.2 mg/100 g BW/h) prevented these hemodynamic disturbances, rendering a significant decrease in the total area of erosions at 20 and 60 min after retransfusion. These results strongly suggest an important role of circulating endothelin in the pathogenesis of hemorrhagic shock-induced gastric mucosal injury through mucosal microcirculatory perturbation.

Animals↗
PubMed1995

Age-related changes in the lipofuscin accumulation of brain and heart.

Lipofuscin is the end-product of intracellular lipid peroxidation and the accumulation results from the cellular metabolism during aging (life stage). We suggested that the accumulation of cardiac lipofuscin was dependent on the specific metabolic rate of mammals. Slower rate of cardiac lipofuscin accumulation (against absolute lifespan) was observed in the animals of larger body size. The rate of cardiac lipofuscin accumulation was correlated with the specific metabolic rate, and inversely correlated with the brain weight of mammals. The first appearance of lipofuscin granules was 8 weeks of age in the hippocampus and in the thalamus. In the case of cerebral cortex (laminae III), lipofuscin granules were first found at 3-month-old rats. The rate of lipofuscin accumulation was the highest in the hippocampus (y = 0.286x - 0.099, r = 0.963) among the three regions examined. In the case of cerebral cortex and thalamus, the slower rate of lipofuscin accumulation was observed (y = 0.072x - 0.14, r = 0.797 for cerebral cortex; y = 0.067X - 0.14, r = 0.953 for thalamus). It is noticed that the most abundant accumulation and the highest rate of lipofuscin accumulation are the hippocampus. Even the hippocampus, the rate and the magnitude of lipofuscin accumulation was low as compared with cardiac muscles. From these results, it is suggested that brains have better protective system against oxidative stress than other organs do.

Aging↗
PubMed1995

Angiotensin II partly mediates mechanical stress-induced cardiac hypertrophy.

We have previously shown that mechanical stress induces activation of protein kinases and increases in specific gene expression and protein synthesis in cardiac myocytes, all of which are similar to those evoked by humoral factors such as growth factors and hormones. Many lines of evidence have suggested that angiotensin II (Ang II) plays a vital role in cardiac hypertrophy, and it has been reported that secretion of Ang II from cultured cardiac myocytes was induced by mechanical stretch. To examine the role of Ang II in mechanical stress-induced cardiac hypertrophy, we stretched neonatal rat cardiac myocytes in the absence or presence of the Ang II receptor antagonists saralasin (an antagonist of both type 1 and type 2 receptors), CV-11974 (a type 1 receptor-specific antagonist), and PD123319 (a type 2 receptor-specific antagonist). Stretching cardiac myocytes by 20% using deformable silicone dishes rapidly increased the activities of mitogen-activated protein (MAP) kinase kinase activators and MAP kinases. Both saralasin and CV-11974 partially inhibited the stretch-induced increases in the activities of both kinases, whereas PD123319 showed no inhibitory effects. Stretching cardiac myocytes increased amino acid incorporation, which was also inhibited by approximately 70% with the pretreatment by saralasin or CV-11974. When the culture medium conditioned by stretching cardiocytes was transferred to nonstretched cardiac myocytes, the increase in MAP kinase activity was observed, and this increase was completely suppressed by saralasin or CV-11974. These results suggest that Ang II plays an important role in mechanical stress-induced cardiac hypertrophy and that there are also other (possibly nonsecretory) factors to induce hypertrophic responses.

Angiotensin II↗
PubMed1995

Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes.

We have previously shown that stretching cardiac myocytes evokes activation of protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and 90-kD ribosomal S6 kinase (p90rsk). To clarify the signal transduction pathways from external mechanical stress to nuclear gene expression in stretch-induced cardiac hypertrophy, we have elucidated protein kinase cascade of phosphorylation by examining the time course of activation of MAP kinase kinase kinases (MAPKKKs), MAP kinase kinase (MAPKK), MAPKs, and p90rsk in neonatal rat cardiac myocytes. Mechanical stretch transiently increased the activity of MAPKKKs. An increase in MAPKKKs activity was first detected at 1 min and maximal activation was observed at 2 min after stretch. The activity of MAPKK was increased by stretch from 1-2 min, with a peak at 5 min after stretch. In addition, MAPKs and p90rsk were maximally activated at 8 min and at 10 approximately 30 min after stretch, respectively. Raf-1 kinase (Raf-1) and (MAPK/extracellular signal-regulated kinase) kinase kinase (MEKK), both of which have MAPKKK activity, were also activated by stretching cardiac myocytes for 2 min. The angiotensin II receptor antagonist partially suppressed activation of Raf-1 and MAPKs by stretch. The stretch-induced hypertrophic responses such as activation of Raf-1 and MAPKs and an increase in amino acid uptake was partially dependent on PKC, while a PKC inhibitor completely abolished MAPK activation by angiotensin II. These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1 and MEKK, MAPKK, MAPKs and p90rsk, and that angiotensin II, which may be secreted from stretched myocytes, may be partly involved in stretch-induced hypertrophic responses by activating PKC.

Amino Acid Sequence↗
PubMed1995

Effect of hydrostatic pressure on the synthesis of outer membrane proteins in Escherichia coli.

We examined the effects of hydrostatic pressure on the synthesis of Escherichia coli outer membrane proteins, particularly for the osmoregulated ImpC and OmpF porins. It was found that the expression of ompC and ompF was markedly reduced during the growth at high pressure, most likely at the transcriptional level. However, the signal transduction processes through the regulatory proteins, EnvZ and OmpR, was not influenced by the environmental pressure. It was also found that the expression of a presumed novel outer membrane protein, named OmpX, was affected by both the medium osmolarity and pressure in a manner independent of the function of EnvZ and OmpR.

Bacterial Outer Membrane Proteins↗
PubMed1995

Antitumor active fucoidan from the brown seaweed, umitoranoo (Sargassum thunbergii).

Neutral and acidic polysaccharides and their protein complexes were fractionated and purified from the brown seaweed umitoranoo (Sargassum thunbergii) by fractional extraction, iron-exchange chromatography, and gel filtration. Thirty-one polysaccharide fractions were obtained and tested for antitumor activity in mice with Ehrlich carcinoma transplanted i.p. Two of the fractions, GIV-A ([alpha]25D -127 degrees and mol. wt., 19,000) and GIV-B ([alpha]25D -110 degrees and mol. wt., 13,500) had such activity. On the basis of chemical and spectral analyses, these compounds were found to be a fucoidan or L-fucan containing approx. 30% sulfate ester groups per fucose residue, about 10% uronic acid, and less than 2% protein.

Animals↗
PubMed1995

Antitumor-active heteroglycans from niohshimeji mushroom, Tricholoma giganteum.

Water-soluble polysaccharide FI and water-insoluble polysaccharides FII, FIII-1, and FIII-2 were obtained from fruiting bodies of Tricholoma giganteum. Polysaccharides were further fractionated by ion-exchange chromatography, gel filtration, and affinity chromatography. The 24 polysaccharide fractions obtained were examined for their antitumor effect on Sarcoma 180 implanted in mice. The following antitumor-active polysaccharides were identified: FIo-a, a mixture of alpha-D-glucan and xyloglucomannan with an average molecular weight of 1.6 x 10(6); FA-1, a beta-D-glucan containing 1% protein and with a molecular weight of 4.0 x 10(4); FII-1, a (1-->3)-beta-D-glucan containing 7.8% protein, with a molecular weight of 5.2 x 10(4); FIII-1-b, a protein-polysaccharide complex (ratio, 37.5:62.5, w/w), with a molecular weight of 6.8 x 10(4) and with xylose, galactose, mannose, and glucose in the polysaccharide moiety (proportions of 8.9:14.9:29.3:46.9 by weight), and FIII-2-a, b, and c, three (1-->6)-beta-D-glucosyl-branched (1-->3)-beta-D-glucans with a molecular weight from 2.6 x 10(5) to 4.1 x 10(5) and containing small amounts of xylose and galactose and 3.5-8.3% protein.

Animals↗
PubMed1995

A rare case of cardiac sarcoidosis in a patient with progressive systemic sclerosis, Sjogren's syndrome, and polymyositis.

A 56-year-old woman with overlap syndrome of progressive systemic sclerosis (PSS), Sjogren's syndrome, and polymyositis is reported. She developed complete atrioventricular (AV) block and progressive bilateral hilar adenopathy, and was diagnosed as having sarcoidosis by histological examination of the hilar lymph nodes biopsied thoracoscopically. Although coexistence of one or two autoimmune diseases with sarcoidosis is not uncommon, coexistence of three or more autoimmune diseases with sarcoidosis is rare. To our knowledge, the described case is the first case in which the three above-mentioned autoimmune diseases were accompanied by myocardial sarcoidosis.

Cardiomyopathies↗
PubMed1995

[A 115-year-old woman: the oldest individual in Japan].

The purpose of this study was to assess the background to the longevity of a 115-year-old woman who was the oldest individual in Japan as of September, 1994. The secrets of her social and medical profile appeared to be hereditary factors, well-balanced meals, no smoking or drinking, sufficient sleep and adequate exercise. From the viewpoints of psychological aspects and comprehensive functional assessment of the elderly, she clearly has a tenacious personality. Furthermore, she has maintained independence in her activities of daily living, and did not suffer from senile dementia until 107 years of age. From the medical standpoint, she has suffered from transient hypertension, but her left ventricle function has remained within the normal echocardiography range and no greatly abnormal values have been observed in blood chemistry tests. She has suffered from pneumonia and urinary tract infection many times since the age of 109, and on these occasions she was promptly admitted to our hospital and received appropriate medical treatment. We consider that this also played an important role in her longevity.

Activities of Daily Living↗
PubMed1995

Characteristics of participants and non-participants in annual mass screening for oral cancer in 60-year-old residents of Tokoname city, Japan.

Three thousand one hundred and twenty three 60-year-old residents of Tokoname city, Japan, were eligible to take part in an ongoing annual mass screening programme for oral cancer and precancer during the years 1986-1990. All received a mailed questionnaire to ascertain details of their personal circumstances, lifestyle factors and medical history. One thousand six hundred and sixty eight (53 per cent) responded and of these, 347 plus an additional 89 non responders, totalling 14 per cent of the sample, subsequently attended for screening. Those screened were significantly more likely than non participants to have taken part in other general health or cancer screening, to report past histories of diseases or conditions with severe subjective symptoms and to have access to the screening facility on foot, by bicycle or by car. There were no significant differences between the groups in their smoking habits or alcohol consumption. Ways of improving compliance in screening are considered and in particular, the need for further strengthening the complementary public education programme to increase its effectiveness is highlighted.

Alcohol Drinking↗
PubMed1995

[Epidermal growth factor (EGF) can induce prostatic buds in the absence of androgens].

We have investigated the prostatic bud induction in the urogenital sinus of fetal rats and mice when the sinuses were cultured with non-androgenic growth factors, and found that epidermal growth factor (EGF) as well as transforming growth factor-alpha (TGF-alpha) powerfully induces the prostatic buds in the absence of androgens even in the androgen-receptor-deficient Tfm sinuses. Immunofluorescence study revealed that endogenous EGF and EGF receptor exist in the sinus mesenchyme of 19.5-day fetal male rats, where many prostatic buds are appearing.

Animals↗
PubMed1994

Production of interleukin-10 by mouse glial cells in culture.

In this study, we examined the production of IL-10 by glial cells in vitro. IL-10 was detected in the culture supernatants of microglia and in the cell lysate of astrocytes by enzyme-linked immunosorbent assay. We also detected IL-10 mRNA and IL-10 receptor mRNA in both microglia and astrocytes. The expression of IL-10 mRNA, as well as the production of IL-10 protein, was enhanced by the stimulation of these cells with lipopolysaccharide(LPS). Recombinant IL-10 effectively suppressed both LPS-induced cytokine production and IFN-gamma-induced class II major histocompatibility complex antigen expression by microglia. These results suggest that IL-10 is produced in the CNS and plays a role as an inhibitory regulator in the CNS cytokine network.

Animals↗
PubMed1994

A novel device of bacterial signal transducers.

The osmoregulatory expression of ompC and ompF in Escherichia coli is mediated by a pair of bacterial signal transduction proteins, EnvZ (sensory kinase) and OmpR (response regulator). We isolated previously multicopy suppressors which can complement a defect in the phosphotransfer signal transduction caused by an envZ deletion mutation. Among such suppressors, arcB and barA are of particular interest because these gene products are unique in the sense that they contain both an autophosphorylated histidine site (or transmitter module) and a phospho-accepting aspartate site (or receiver module) in their primary amino acid sequences. Here we report that ArcB and BarA possess in the C-terminal region a phosphorylated histidine site which has never been noticed, in addition to the authentic one identified previously. This newly identified histidine in ArcB and BarA was demonstrated to play a crucial role in the observed multicopy suppression. Furthermore, it was demonstrated in vivo and in vitro for ArcB that the C-terminal domain containing the histidine can function as an alternative phosphodonor (or transmitter). This novel type of sensory kinase was therefore revealed to contain two independent phosphodonor sites, together with a phospho-accepting site. These findings suggest that this unique feature of ArcB and BarA, in terms of the signaling modules, make it possible for these sensory kinases to function as dual-signaling transducers.

Amino Acid Sequence↗
PubMed1994

Age-related accumulation of lipofuscin in three different regions of rat brain.

The rate of accumulation of auto-fluorescent granules (lipofuscin) in three different regions of rat brain was investigated at various ages from very young to old animals (1, 2, 3, 6, 12 and 30-34 months of age. The accumulation of lipofuscin increased with age in the three brain regions. The first appearance of lipofuscin granules was at 8 weeks of age in the hippocampus and in the thalamus. In the case of cerebral cortex (laminae III), lipofuscin granules were first found in 3-month-old rats. The rate of lipofuscin accumulation was the highest in the hippocampus (y = 0.286x - 0.099, r = 0.963) among the three regions examined. In the case of cerebral cortex and thalamus, a slower rate of lipofuscin accumulation was observed (y = 0.072x - 0.14, r = 0.797 for cerebral cortex; y = 0.067x - 0.14, r = 0.953 for thalamus). It was noted that the most abundant accumulation and the highest rate of lipofuscin accumulation was in the hippocampus. But the rate and magnitude of lipofuscin accumulation in the hippocampus were low compared with cardiac muscles. From these results, it is suggested that brains have better protective system against oxidative stress than other organs.

Aging↗
PubMed1994

Gene activation by the Escherichia coli positive regulator, OmpR. Phosphorylation-independent mechanism of activation by an OmpR mutant.

In Escherichia coli, expression of the major outer membrane proteins, OmpC and OmpF, is regulated through the functions of OmpR and EnvZ at the transcriptional level in response to the medium osmolarity. OmpR is the crucial activator that helps RNA polymerase to efficiently trigger ompC and ompF transcription. This OmpR function is modulated by phosphorylation mediated by the cognate sensory kinase, EnvZ. Phosphorylation at the N-terminal domain of OmpR results in substantial enhancement of the DNA-binding ability of the C-terminal domain, thereby allowing the activation of ompC and ompF transcription by OmpR. Here we isolated an OmpR mutant which lacks the N-terminal half, but can enhance transcription in vivo. This novel type of OmpR mutant was revealed to have a single amino acid replacement of Gly227 to Cys. The newly-introduced-Cys residue allows OmpR molecules to form a stable dimer in vitro without the help of the N-terminal half. This altered C-terminal half is able to bind efficiently and specifically to the cognate DNA in vitro. It can function as an activator for ompC transcription in vitro in a phosphorylation-independent manner. These results suggest that the putative activator domain of OmpR, together with the DNA-binding domain, is most likely located in the C-terminal half. They also suggested that the phosphorylation of OmpR may not be essential for gene activation per se.

Bacterial Outer Membrane Proteins↗
PubMed1994

Mechanism of gene activation by the Escherichia coli positive regulator, OmpR: a mutant defective in transcriptional activation.

The OmpR protein is an activator specific for the E. coli ompC and ompF genes. This protein functions in a phosphorylation-dependent manner through a presumed interaction with RNA polymerase. In this study we isolated OmpR mutants which were suggested to be defective for transcriptional activation, but not for DNA binding. Two such mutants, that we isolated, have a single amino acid alteration at positions 131 [P131S], and 179 [P179L], respectively, of OmpR, comprising 239 amino acids. These altered amino acids in OmpR may be implicated, directly or indirectly, in the presumed RNA polymerase/OmpR interaction that is important for transcriptional activation.

Bacterial Outer Membrane Proteins↗
PubMed1994

Spontaneous acetylcholine release in the hippocampus exhibits a diurnal variation in both young and old rats.

Extracellular levels of acetylcholine (ACh) in the hippocampus were measured by the microdialysis method in freely moving young (3-4 months old) and old (18-24 months old) female rats over a period of 24 h to examine the effect of aging on hippocampal ACh release. Hippocampal ACh release during a 24-h period exhibited a diurnal variation with higher levels during the dark cycle than during the light cycle in old rats as well as young rats. The present study suggests that a diurnal variation in ACh release is maintained fairly well until the rats are at least 24 months old.

Acetylcholine↗