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Biomedical subjects

S Masuda

Publications and source records attributed to S Masuda.

At least 109 records · Page 6Linked to original sources

[A case of metachronous lung cancer in which tumor developed within the different ipsilateral lobe over a short period of time and completion pneumonectomy was required].

A 51-year-old man underwent a middle-lower lobectomy for squamous cell carcinoma on February 8, 1996. In July, 1997, a computed tomography revealed a mass shadow in the right upper lung field. Completion pneumonectomy was performed. Histopathological examination showed poorly differentiated adenocarcinoma. This case was the shortest time to occurrence of second tumor in our metachronous lung cancer cases. We must always give attention to exist second primary lung cancer and double primary lung cancer after resection of primary lung cancer.

Adenocarcinoma↗

[A case of superior mediastinal neurinoma resected from the supra-clavicular area].

We report a case of superior mediastinal neurinoma that was resected from the supra-clavicular area. An abnormal shadow on the chest X-ray film was pointed out in a 53-year-old male. A left supra-clavicular mass was subsequently also discovered. We underwent extirpation of the tumor through supra-clavicular approach and confirmed to be a neurinoma histologically. We consider supra-clavicular approach which allows a good view might be useful.

Humans↗

[Vitamin D: its chemistry, metabolism and biological functions].

Vitamin D is metabolized to 25-hydroxyvitamin D(25(OH)D) in the liver and subsequently to 1 alpha,25-dihydroxyvitamin D(1 alpha,25(OH)2D) or 24R,25-dihydroxyvitamin D(24R,25(OH)2D) in the kidney. 1 alpha,25(OH)2D, the active form of vitamin D, stimulates intestinal calcium absorption and bone resorption, resulting in the elevation of plasma calcium. Recent studies have revealed that 1 alpha,25(OH)2D exerts a wide variety of biological actions such as cellular differentiation and proliferation in addition to its role in calcium homeostasis. Most cellular actions of 1 alpha,25(OH)2D are mediated by alterations in the transcription of vitamin D-dependent genes. In this review article, the mode of action and the biological function of 1 alpha,25(OH)2D are summarized.

Humans↗

Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery.

Erythropoietin (EPO) prevents the ischemia-induced delayed neuronal death in the hippocampal CA1 field in gerbils. EPO receptor (EPOR) is also expressed in the cerebral cortex but its function is not known. To examine whether EPO has a neuroprotective action in the cortex, EPO was infused into the cerebroventricles of stroke-prone spontaneously hypertensive rats with permanent occlusion of the left middle cerebral artery. Morris water maze test indicated that EPO infusion alleviated the ischemia-induced place navigation disability. The left (ischemic)-to-right (contralateral nonischemic) (L/R) ratio of cerebrocortical area in the EPO-infused ischemic group was larger than that in the vehicle-infused ischemic group. The occlusion caused secondary thalamic degeneration but infusion of EPO prevented the decrease in the L/R ratio of thalamic area and supported neuron survival in the ventroposterior thalamic nucleus. In situ hybridization indicated that EPOR mRNA was upregulated in the periphery (ischemic penumbra) of a cerebrocortical infarct after occlusion of the middle cerebral artery, suggesting that an increased number of EPOR in neurons facilitates the EPO signal transmission, thereby preventing the damaged area from enlarging.

Animals↗

Correlation between potentiation of AP1 DNA binding and expression of c-Fos in association with phosphorylation of CREB at serine133 in thalamus of gerbils with ischemia.

Protein biosynthesis is mainly under the control at the level of gene transcription in eukaryotes. Transcription factors are nuclear proteins with abilities to modulate the activity of RNA polymerase II which is responsible for the formation of messenger RNA from double stranded DNA in the cell nuclei. Binding of a radiolabeled oligonucleotide probe for the transcription factor activator protein-1 (AP1) was transiently potentiated 1 to 6 h after the recirculation of blood supply in the thalamus and striatum, but not in the entorhinal cortex, olfactory bulb, frontal cortex, cerebellar cortex and medulla-pons, in gerbils with transient global forebrain ischemia for 5 min, in addition to the hippocampal subregions. The ischemic insult not only increased the immunoreactivity with an antibody against cyclic AMP response element binding protein (CREB) phosphorylated at serine133, but also induced the expression of both c-Jun and c-Fos family proteins 3 h after the recirculation in the thalamus. Limited proteolysis by Staphylococcus aureus (S. aureus) V8 protease revealed the expression of different partner proteins of AP1 in response to ischemic signals in the thalamus. Moreover, ischemia for 2 min led to more prolonged elevation of AP1 binding in the thalamus at least up to 12 h after the reperfusion than that seen with ischemia for 5 min. These results suggest that potentiation of AP1 DNA binding may at least in part involve mechanisms associated with the expression of c-Fos protein through phosphorylation of CREB at serine133 in the thalamus of gerbils with ischemia.

Amino Acid Sequence↗

Estrogen-dependent production of erythropoietin in uterus and its implication in uterine angiogenesis.

Although erythropoietin (Epo) has been shown to possess in vitro angiogenic activity, its physiological significance has not been demonstrated. Normally angiogenesis does not occur actively in adults but an exception is the female reproductive organ. In the uterine endometrium, angiogenesis takes place actively for supporting the endometrial growth that occurs during transition from the diestrus to estrous stage. This transition is under control of 17beta-estradiol (E2), an ovarian hormone, and can be mimicked by injection of E2 to ovariectomized (OVX) mouse. Thus, the uterus is a pertinent site to examine the Epo function in angiogenesis. We found that Epo protein and its mRNA were produced in an E2-dependent manner, when the uterus from OVX mouse was cultured in vitro. The de novo protein synthesis was not needed for E2 induction of Epo mRNA. Administration of E2 to OVX mouse induced a rapid and transient increase in Epo mRNA in the uterus. Injection of Epo into the OVX mouse uterine cavity promoted blood vessel formation in the endometrium. Furthermore, injection of the soluble Epo receptor capable of binding with Epo into the uterine cavity of non-OVX mouse in diestrus stage inhibited the endometrial transition to proestrus stage, whereas heat-inactivated soluble Epo receptor allowed the transition to occur. These results, combined with our finding that the endothelial cells in uterine endometrium express Epo receptor, strongly suggest that Epo is an important factor for the E2-dependent cyclical angiogenesis in uterus.

Animals↗

In vivo evidence that erythropoietin protects neurons from ischemic damage.

Erythropoietin (EPO) produced by the kidney and the liver (in fetuses) stimulates erythropoiesis. In the central nervous system, neurons express EPO receptor (EPOR) and astrocytes produce EPO. EPO has been shown to protect primary cultured neurons from N-methyl-D-aspartate (NMDA) receptor-mediated glutamate toxicity. Here we report in vivo evidence that EPO protects neurons against ischemia-induced cell death. Infusion of EPO into the lateral ventricles of gerbils prevented ischemia-induced learning disability and rescued hippocampal CA1 neurons from lethal ischemic damage. The neuroprotective action of exogenous EPO was also confirmed by counting synapses in the hippocampal CA1 region. Infusion of soluble EPOR (an extracellular domain capable of binding with the ligand) into animals given a mild ischemic treatment that did not produce neuronal damage, caused neuronal degeneration and impaired learning ability, whereas infusion of the heat-denatured soluble EPOR was not detrimental, demonstrating that the endogenous brain EPO is crucial for neuronal survival. The presence of EPO in neuron cultures did not repress a NMDA receptor-mediated increase in intracellular Ca2+, but rescued the neurons from NO-induced death. Taken together EPO may exert its neuroprotective effect by reducing the NO-mediated formation of free radicals or antagonizing their toxicity.

Animals↗

Two vascular apoptosis-inducing proteins from snake venom are members of the metalloprotease/disintegrin family.

Hemorrhagic snake venom induces apoptosis in vascular endothelial cells. In a previous report, we described the purification of a vascular apoptosis-inducing protein (VAP) from Crotalus atrox [Masuda, S., Araki, S., Kaji, K. & Hayashi, H. (1997) Biochem. Biophys. Res. Commun. 235, 59-63]. We report here the identification of a second vascular apoptosis-inducing protein, VAP2, in venom from C. atrox. When we fractionated crude venom from C. atrox by isoelectric focusing, we found two proteins with apoptosis-inducing activity, one was basic and the other acidic. The basic protein corresponded to VAP, and we named the acidic protein VAP2. VAP2 was a monomeric protein with molecular mass of 55 kDa and an isoelectric point of 4.5. VAP2 killed vascular endothelial cells in culture, and the death of cells exhibited the characteristic features of apoptotic activity of VAP2 seemed to be specific to endothelial cells, as reported for VAP. The half-lethal doses of VAP and VAP2 were 0.3 microg/ml and 0.1 microg/ml, respectively. Analysis of the partial amino acid sequences of VAP and VAP2 revealed similarities to members of the metalloprotease/disintegrin family. The sensitivity of VAP2 to changes in pH and temperature was distinct from that of VAP. Our results suggest that VAP and VAP2 are members of the metalloprotease/disintegrin family.

Amino Acid Sequence↗

Prolongation by bifemelane of potentiation of AP1 DNA binding in hippocampal CA1 subfield of gerbils with transient forebrain ischemia.

In eukaryotes, protein de novo synthesis is mainly under the control of transcription factors at the level of gene transcription in cell nuclei. Gel retardation electrophoresis was employed for determination of DNA-binding activity of the transcription factor activator protein-1 (AP1), which is a dimer between c-Fos and c-Jun protein families. Binding of a radiolabeled double-stranded oligonucleotide probe for AP1 was rapidly potentiated in the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of gerbils with forebrain ischemia for 5 min. Similarly marked potentiation was seen in the thalamus and the striatum, but not in the frontal cortex, following the recirculation of blood supply. The potentiation was transient in the vulnerable CA1 subfield, but was rather persistent in the thalamus and the striatum in addition to the resistant CA3 subfield and dentate gyrus. However, administration of the neuroprotective drug bifemelane (10 to 20 mg/kg, i.p.) resulted in prolongation of the potentiation of AP1 binding in the CA1 subfield up to 6 hr after ischemia, without significantly affecting that in other central structures. Limited proteolysis revealed that bifemelane induced expression of the AP1 consisting of constructive proteins different from those expressed in control animals in the CA1 subfield. These results suggest that bifemelane may protect neuronal cells against ischemic injuries through molecular mechanisms associated with prolongation of the potentiation of AP1 binding in the vulnerable CA1 subfield after ischemia.

Animals↗

Embryonal carcinoma P19 cells produce erythropoietin constitutively but express lactate dehydrogenase in an oxygen-dependent manner.

Embryonic stem cells and embryonal carcinoma P19 cells produce erythropoietin (Epo) in an oxygen-independent manner, although lactate dehydrogenase A (LDHA) is hypoxia-inducible. To explore this paradox, we studied the operation of cis-acting sequences from these genes in P19 and Hep3B cells. The Epo gene promoter and 3' enhancer from P19 cells conveyed hypoxia-inducible responses in Hep3B cells but not in P19 cells. Together with DNA sequencing and the normal transcription start site of P19 Epo gene, this excluded the possibility that the noninducibility of Epo gene in P19 cells was due to mutation in these sequences or unusual initiation of transcription. In contrast, reporter constructs containing LDHA enhancer and promoter were hypoxia inducible in P19 and Hep3B cells, and mutation of a hypoxia- inducible factor 1 (HIF-1) binding site abolished the hypoxic inducibility in both cells, indicating that HIF-1 activation operates normally in P19 cells. Neither forced expression of hepatocyte nuclear factor 4 in P19 cells nor deletion of its binding site from the Epo enhancer was effective in restoring Epo enhancer function. P19 cells may lack an unidentified regulator(s) required for interaction of the Epo enhancer with Epo and LDHA promoters.

Base Sequence↗

The effects of a myocardial bridge on coronary atherosclerosis and ischaemia.

The term myocardial bridge (MB) describes the surprisingly common situation in which part of the left anterior descending coronary artery (LAD), running in epicardial adipose tissue, is covered by a bridge of myocardial tissue. The presence of an MB may influence arterial tissue through the alteration of haemodynamic forces by the myocardial contraction of the bridge itself. Histopathologically and ultrastructurally, any manifestations of atherosclerosis elsewhere in the LAD are suppressed in the intima beneath the MB. By scanning electron microscopy, abrupt changes in endothelial cell morphology indicate that the intima beneath the bridge is protected by haemodynamic factors. Furthermore, the closer the bridge to the left coronary ostium, the greater the extent of proximal intimal thickening. In parallel with this, considering the occurrence of myocardial infarction in cases of proximal MB together with previous reports on relationships between MB and coronary ischaemia, it appears that anatomical characteristics such as the location, length, and thickness of the MB have a bearing on the effects of this abnormality. When the pathologist examines the heart at autopsy, this quite common condition should be borne in mind, in view of its potential but complex relationship to atherosclerosis and ischaemic heart disease.

Aged↗

Molecular cloning and nucleotide sequence of the pyruvate kinase gene of an actinomycete Microbispora thermodiastatica.

The gene for the thermostable pyruvate kinase of Microbispora thermodiastatica IFO 14046, a moderate thermophilic actinomycete, was cloned in Escherichia coli. This gene consists of an open reading frame of 1422 nucleotides and encodes a protein of 474 amino acids with molecular mass of 50,805 Da. The open reading frame was confirmed as the pyruvate kinase gene by comparison with the N-terminal amino acid sequence of the purified pyruvate kinase from M. thermodiastatica.

Actinomycetaceae↗

Possible involvement of activator protein-1 DNA binding in mechanisms underlying ischemic tolerance in the CA1 subfield of gerbil hippocampus.

Transcription factors are nuclear proteins with an ability to recognize particular nucleotide sequences on double stranded genomic DNAs and thereby modulate the activity of RNA polymerase II which is responsible for the formation of messenger RNAs in cell nuclei. Gel retardation electrophoresis revealed that transient forebrain ischemia for 5 min led to drastic potentiation of binding of a radiolabelled double-stranded oligonucleotide probe for the transcription factor activator protein-1, in the thalamus as well as the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of the gerbils previously given ischemia for 2 min two days before, which is known to induce tolerance to subsequent severe ischemia in the CA1 subfield. By contrast, ischemia for 5 min resulted in prolonged potentiation of activator protein-1 binding in the vulnerable CA1 subfield of the gerbils with prior ischemia for 5 min 14 days before, which is shown to induce delayed death of the pyramidal neurons exclusively in this subfield. Similar prolongation was seen with activator protein-1 binding in the vulnerable thalamus but not in the resistant CA3 subfield and dentate gyrus of the gerbils with such repeated ischemia for 5 min. Limited proteolysis by Staphylococcus aureus V8 protease as well as supershift assays using antibodies against c-Fos and c-Jun proteins demonstrated the possible difference in constructive partner proteins of activator protein-1 among nuclear extracts of the CA1 subfield obtained from gerbils with single, tolerated and repeated ischemia. These results suggest that de novo protein synthesis may underlie molecular mechanisms associated with acquisition of the ischemic tolerance through modulation at the level of gene transcription by activator protein-1 composed of different constructive partner proteins in the CA1 subfield. Possible participation of glial cells in the modulation is also suggested in particular situations.

Animals↗

Inhibitory effect of bacterial attachment on candidal growth due to adherence with mannose-sensitive pili.

A bacterial strain with affinity to Candida albicans was successfully obtained from a natural environment. An uncovered Petri dish containing a suspension of heat-killed C. albicans cells was allowed to stand in a laboratory for several days. Some bacteria which had adhered to the candidal cells were tested for their ability to agglutinate the cells. A bacterial strain, designated later as CAB-1, was found to agglutinate candidal cells through bridging by mannose-sensitive pili. CAB-1 showed similar bacteriological characteristics to those of Citrobacter freundii by ID test. The adherence of CAB-1 to candidal cell was precisely presented by scanning electron microscopy. The inhibitory effect of CAB-1 attachment to candidal cells on the growth of Candida was also preliminarily confirmed.

Agglutination↗

Occurrence of coagulase serotype among Staphylococcus aureus strains isolated from healthy individuals--special reference to correlation with size of protein-A gene--.

One-hundred-and-nineteen strains of Staphylococcus aureus isolated from healthy individuals for 3 years between 1991 and 1993 were subjected to an investigation on the producibility of proteins including protein A, coagulase, enterotoxins and toxic-shock syndrome toxin-1. Especially, protein A was the center of our interest. Among these strains, 69, 43, 3 and 1 strains were found to have the protein-A gene containing 5, 4, 3 and 2 IgG-binding domains, respectively. On the other hand, only one strain was devoid of the protein-A gene. There were some differences in the profile of the coagulase serotype between the group with 4 IgG-binding domains and that with 5 IgG-binding domains. Differences in the profile of toxin production were also observed between the two groups.

Coagulase↗