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Biomedical subjects

S Ueda

Publications and source records attributed to S Ueda.

At least 523 records · Page 29Linked to original sources

Tumour necrosis factor-alpha can modulate the phenotype of aortic smooth muscle cells.

In culture, rabbit aortic smooth muscle cells (SMC) from an atheroma differed phenotypically from SMC from normal media (M-SMC) in their growth rate, secretion of SMC-derived growth factor (SDGF), and metabolism of acetylated low density lipoproteins (a-LDL). The factor responsible for this in vivo phenotypic change of SMC was investigated in vitro. After preincubation of M-SMC with 0.1-10 U ml-1 of tumour necrosis factor-alpha (TNF) for 1-3 days, the cells grew faster than control cells and secreted a substantial amount of SDGF. The population doubling time and secretion of SDGF were inversely correlated. Moreover, after preincubation with TNF, the SMC metabolized [125I]a-LDL, unlike control M-SMC. These findings show that TNF can modulate the phenotype of SMC and suggest that it is important in the pathogenesis of atherosclerosis.

Animals↗

[A case of primary systemic amyloidosis with skeletal muscle atrophy and congestive heart failure].

A 77-year-old male had been noticing progressive weakness of the legs for three years. By the age of 75 he had difficulty in climbing stairs. On admission, serum level of CPK was moderately high. There were weakness and atrophy of the proximal muscles. Deep tendon reflexes were depressed. Sensation was normal. The electromyogram and the biopsy of the femoral quadriceps muscles showed nonspecific changes. In 1989, he developed difficulty in walking and had congestive heart failure. On the second admission, moist rales were heard over the chest, and pitting edema was present in the lower extremities. The chest roentgenogram showed a cardiothoracic ratio of 63% and bilateral pleural effusion. The electrocardiogram showed atrial flutter with 2:1 conduction, QS in V1-3, rS in V4, and ST depression and T inversion in V5,6. The echocardiogram revealed a thick left ventricular wall and impaired left ventricular contraction (EF 22%). Macroglossia, hepatosplenomegaly and renal dysfunction were not noted. Congestive heart failure progressed and he suddenly died of ventricular tachycardia in December 1989. At autopsy, skeletal muscle fibers varied in size and showed fiber splitting. A cellular infiltration was observed in the stroma. Amyloid deposit was positively stained with Congo red. The heart weight was 570 g with marked left ventricular hypertrophy and moderate bilateral atrial dilatation. In both atria and ventricles, extensive amyloid deposition was found around myocardial fibers as well as in perivascular spaces. Amyloid was present also in the liver, the kidneys, the gastrointestinal tracts, and the other organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Frequency of IFN beta 1 gene loss in 47 primary human gliomas.

Loss of genetic information from a number of specific regions of the genome has been documented in primary human gliomas. Recently loss of heterozygosity or nullizygosity of the IFN beta 1 gene has been found in glioblastomas. We used Restriction Fragment Length Polymorphism (RFLP) analysis in order to screen the frequency of the loss of this genes in glial tumors of malignancy grades I-IV. Nullizygosity for IFN beta 1 was detected in 8/30 (27%) of glioblastomas (malignancy grade IV) and loss of heterozygosity in a further two cases (7%). In total, 33% of these tumors lost least one copy of the IFN beta 1 gene. Among the 10 anaplastic gliomas (grade III), 2 (20%) showed loss of one copy of the gene which none of the 7 low grade gliomas (grades I or II) showed any evidence of loss of IFN beta 1 alleles. The loss of the IFN beta 1 gene would appear to be a late event associated with the development of an increasingly malignant phenotype in human gliomas and to be confined to gliomas of malignancy grade III or IV.

Adolescent↗

[An application of molecular cell biology to visualize and manipulate gene expressions of specific proteins in the neuroendocrine and pituitary systems].

Tremendous progress in molecular biology has made it possible to investigate the gene structure of proteins which maintain the internal environment of the living tissue. A wide variety of proteins is required for the diverse functions of the nervous and endocrine systems, because they contain a heterogeneous population of highly specialized cells. The proteins in the cell are all derived from specific genes which encode the sequences of amino acids through the process of gene expression. Four stages are involved in gene expression; transcription, processing of RNA, translation, and post-translational processing. In situ hybridization is a powerful technique to detect specific mRNA at the cellular level with microscopic resolution. Antisense method also has an impact upon gene expression. The basic idea of both in situ hybridization and antisense method is that nucleotides complementary to a specific mRNA will bind to the mRNA as a probe to detect its location or as an inhibitor to block processing or translation. In this paper, molecular cell biology, particularly in situ hybridization and antisense methods is described to localize the site of specific gene expression of biochemical messengers in the neuroendocrine and pituitary systems.

Animals↗

[Changes in right ventricular hemodynamic function by unilateral pulmonary arterial occlusion test].

We performed unilateral pulmonary arterial occlusion test (UPAO) for the preoperative evaluation of lung function in patients undergoing lung resection. In this test, the main pulmonary artery of either side is occluded to simulate postoperative functional status. In order to evaluate the right ventricular hemodynamic function, we measured right ventricular ejection fraction (RVEF) and right ventricular end-diastolic volume index (RVEDVI) throughout UPAO by thermodilution method. We investigated the relationships between changes in right ventricular hemodynamic function and postoperative complications related to cardiac functions, namely arrhythmias or heart failure. Thirty-four patients without heart disease prior to lung resection were examined by UPAO, and RVEF and RVEDVI were measured. Analyses demonstrated that changes in RVEF were inversely correlated with changes in RVEDVI. In 6 cases, RVEDVI increased from control by over 20% during UPAO. All of these patients had postoperative cardiac complications. The hypothetical ventricular function curves showed a large increase in RVEDVI relative to right ventricular stroke work index (RVSWI), suggesting a decrease in right ventricular function. In conclusion, these results suggest that changes in RVEDVI during UPAO may predict postoperative cardiac complications in patients undergoing pulmonary resection.

Adult↗

Significance of endothelial deposition of von Willebrand factor in thrombotic thrombocytopenic purpura: autopsy findings of a case complicated with systemic lupus erythematosus.

We report the renal immunohistochemical findings of a patient with thrombotic thrombocytopenic purpura complicated with systemic lupus erythematosus. Aggregated platelets were observed adhering to the arteriole walls. Intense deposition of von Willebrand factor (vWF) was noted in the endothelium, even in areas where thrombi were not seen. This difference in the distribution of platelets and vWF suggested that the endothelium was damaged prior to platelet aggregation.

Aged↗

Individual DNA identification from ancient human remains.

Individual identification of ancient human remains is one of the most fundamental requisites for studies of paleo-population genetics, including kinship among ancient people, intra- and interpopulation structures in ancient times, and the origin of human populations. However, knowledge of these subjects has been based mainly on circumstantial archaeological evidence for kinship and intrapopulation structure and on genetic studies of modern human populations. Here we describe individual identification of ancient humans by using short-nucleotide tandem repeats and mtDNAs as genetic markers. The application of this approach to kinship analysis shows clearly the presence or absence of kinship among the ancient remains examined.

Adult↗

Phosphoinositide turnover imaging linked to muscarinic cholinergic receptor in the central nervous system by positron emission tomography.

Receptor-mediated membrane processing plays an essential role in neural function in the synapses. In such neurotransmission process, the phosphoinositide (PI) response, an effector in the production of second-messengers, can be used to assess in vivo signal transduction. Using in vivo autoradiography and positron emission tomography (PET), we attempted to visualize the PI response to muscarinic cholinergic receptor (mAChR)-stimulation in rats and monkeys, which were administered 1,2-[11C]diacylglycerol (DAG) intravenously. Enhancement of 1,2-[11C]DAG incorporation was observed in the rat ipsilateral hippocampus and cortex in which mAChR-agonist was administered by local injection, but this was in contrast to spreading cortical depression in the ipsilateral cortex using KCl. In monkey PET studies, dynamic brain scanning revealed increase in activity over time for about 15 min after a bolus injection of 1,2-[11C]DAG in an awake state. The activity then remained at a constant level. This finding documented the theoretical "membrane-trapping" mechanism. The systemic mAChR-stimulation accelerated incorporation in the cerebral cortices of the same monkey brain. Radioactivity uptake did not differ significantly between the mAChR-stimulated and nonstimulated early scan images. This suggested that cerebral blood flow does not greatly affect DAG incorporation. In sequential membrane processes of PI turnover, diacylglycerol kinase rapidly metabolizes DAG, included in PI turnover. In conclusion 1,2-[11C]DAG incorporation was limited by receptor-mediated PI turnover, which can represent real synaptic transmission in neural networks.

Animals↗

Protein kinase C imaging using carbon-11-labeled phorbol esters: 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate as the potential ligand for positron emission tomography.

Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions in the nervous system. Tumor-promoting phorbol esters can substitute for diacylglycerols which are important ligands that bind to protein kinase C. Three typical phorbol esters, phorbol 13-[1-11C]butyrate, phorbol 12,13-[1-11C]dibutyrate and 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate, were synthesized by using [11C]ethylketene with a high specific activity (186GBq/mumol). Their in vivo autoradiograms demonstrated a heterogenous distribution in rat brain. 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate was particularly suited for in vivo use due to its nontumor-promoting activity and its ready permeability to the blood-brain barrier. High optical density was observed in the cortex, amygdala and hippocampus. The in vivo binding properties of this compound to protein kinase C were confirmed by in vivo displacement studies with unlabeled 12-deoxyphorbol 13-isobutyrate-20-butyrate and unlabeled phorbol 12,13-dibutyrate. This suggests that 12-deoxyphorbol 13-isobutyrate-20-[1-11C] butyrate has a specific binding affinity for protein kinase C.

Animals↗

[Extension of functional limitation for surgery of lung cancer by unilateral pulmonary arterial occlusion test].

We performed unilateral pulmonary arterial occlusion test to determine the indication for lung resection functionally, and investigated 32 cases whose total pulmonary vascular resistance was over 700 dyne.sec.cm-5/M2. Thirteen out of 32 cases underwent surgery. There was no difference in lung function tests between surgical and non-surgical cases. Nine out of 12 cases whose pulmonary vascular resistance was less than 800 dyne by unilateral pulmonary arterial occlusion test underwent surgery, and none of these cases died within 3 months after surgery. In non-surgical cases, two were aged patients and one had chronic renal failure. Four out of 20 cases whose total pulmonary vascular resistance was over 800 dyne underwent surgery. Two cases that underwent surgery died within 3 months after surgery. These results suggest that the functional limitation of lung resection can be extended from 700 dyne.sec.cm-5/M2 to 800 dyne.sec.cm-5/M2 total pulmonary vascular resistance by application of unilateral pulmonary arterial occlusion test.

Aged↗

Effects of phorbol ester on lower urinary tract smooth muscles in rabbits.

The contractile effects of phorbol 12,13-dibutyrate (PDBu) on rabbit urinary bladder dome and urethra were investigated using muscle bath techniques. PDBu caused concentration-dependent contractions in both tissues, and these responses were not affected by pretreatment with atropine, phentolamine, hexamethonium or indomethacin. In both tissues, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinase C (PKC), inhibited PDBu-induced contractions in a concentration-dependent manner. The maximum PDBu-induced contractions in bladder dome and urethra were 33.5 +/- 3.4 and 33.3 +/- 4.1% of KCl-induced maximum contractions, respectively. In Ca(2+)-free solution or after pretreatment with nifedipine (10(-6) M), PDBu-induced contractions were reduced but not completely abolished. Although pretreatment with PDBu (10(-8) M) did not have a significant effect on the contractile responses induced by carbachol (in bladder dome) and phenylephrine (in urethra), pretreatment with H-7 (100 microM) had an inhibitory effect on carbachol- and phenylephrine-induced contractions; tonic phase contractions were more sensitive than phasic contractions. These results indicate that PDBu has significant contractile effects in rabbit bladder dome and urethra, and that the effects may be partly mediated by activation of PKC. PKC activation might also contribute to agonist-induced contractile responses in these tissues.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Development of peptide- and tyrosine hydroxylase-containing neurons in the fetal spinal cord transplanted into the anterior chamber of the eye of adult rats.

Fetal rat spinal cord transplanted into the anterior chamber of the eye of an adult rat was immunohistochemically stained using antisera to substance P (SP), neuropeptide Y (NPY), methionine-enkephalin (ENK), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), and distributional changes of peptide- and enzyme-containing neurons 1, 2 and 4 weeks after transplantation were investigated. To examine the effect of colchicine on immunoreactivity, unilateral eyes of these adult host rats received intraocular colchicine treatment. Without colchicine treatment, numerous SP- and CGRP-immunoreactive (IR) neurons were observed in the graft 1 week after transplantation, and their immunoreactivity gradually decreased up to 4 weeks after transplantation. NPY-, ENK-and VIP-IR neurons first appeared in the graft 2 weeks after transplantation. Four weeks after transplantation, the immunoreactivity of NPY and ENK decreased significantly, whereas VIP-IR neurons showed the same intensity as that observed at 2 weeks after transplantation. TH-IR neurons, on the other hand, were seen at every stage, but their immunoreactivity was constant all the time. After colchicine treatment, the number of SP-, NPY-, ENK- and CGRP-IR neurons appeared to increase, while that of VIP- and TH-IR neurons did not change significantly. The distribution patterns of the peptide- and enzyme-containing fibers differed from each other. In the analysis of serial sections stained with 5 peptides (SP, NPY, ENK, VIP, CGRP), fibers containing these peptides were found to be densely accumulated in specific areas of the transplanted spinal cord. The present findings demonstrated that most of the peptide- and enzyme-containing neuron systems in the transplanted spinal cord showed similar distribution patterns and development to those in the normal spinal cord, but that some displayed different distribution.

Animals↗

Isolation and characterization of conglutinin as an influenza A virus inhibitor.

Normal horse and guinea pig sera contain alpha 2-macroglobulin which inhibits the infectivity and hemagglutinating activity of influenza A viruses of the H2 and H3 subtypes. On the other hand, normal bovine serum contains a component termed beta inhibitor that inhibits the infectivity and hemagglutinating activity of influenza A viruses of the H1 and H3 subtypes. To investigate the nature of the beta inhibitor of influenza A virus, we purified the conglutinin and examined its characteristics. First, we found a high correlation between the hemagglutination inhibition(HI) titer and conglutinin titer in several bovine sera (r = 0.906, p less than 0.005). The HI of bovine serum was mainly dependent on conglutinin because the HI activity was abrogated by N-acetylglucosamine but not by D-mannose. The conglutinin, purified from bovine serum, had neutralizing-activity as well as HI activity on influenza A viruses of the H1 and H3 subtypes. The HI activity of conglutinin was heat stable (56 degrees C, 30 min), Ca(++)-dependent, and resistant to both neuraminidase and periodate treatments. The HI activity of purified conglutinin was blocked by N-acetylglucosamine but not by D-mannose. The conglutinin was bound to hemagglutinin which had high mannose and complex sugar chains and its binding was inhibited by N-acetylglucosamine and dependent on divalent cations. These data indicate that the beta-like inhibitor activity of bovine serum is mainly dependent on conglutinin which inhibits hemagglutination and neutralizes the virus infectivity by its binding to a carbohydrate site at the HA.

Animals↗