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Biomedical subjects

T Doi

Publications and source records attributed to T Doi.

At least 379 records · Page 21Linked to original sources

[A new computerized system for electroencephalography at the Kochi Medical School Hospital: the present status and problems of electroencephalogram data filing systems].

The usual electroencephalography (EEG) recording consumes great amounts of paper, considerable storage space for records and much time and energy for their search and retrieval. In addition, we can not perform digitized analyses of the records with the present method. To solve these problems, our laboratory developed a new computerized system for EEG, in which data are retained in optic disks, and which has been in service for routine examination since December, 1988. The functions of the system and EEG filing system, include the collection, retention, retrieval, transmission and analyses of data with the reproduction of the original EEG and editing function of summary reports to be filed in the medical records. The summary report consists of summary, characteristic wave patterns picked up and edited from EEG, and spectral array and topographical mapping by digitized analyses of EEG. The condition for the collection of EEG data was 200 Hz/8 bit, and the reproduced wave patterns were accepted by all clinicians. The merits of the system include; (i) saving of paper, space and time needed for EEG, (ii) enabling the comparison of the wave patterns in the form of summary reports and (iii) the capability of digitized analyses of EEG by retaining the EEG data in the data base. The problems remaining to be improved for the system are the longer time required for examination (5-10 min) and the higher running cost (yen 460/order). Regarding the latter problem, a revised method which dispenses with recording paper is under consideration. That is, in the case of screening examinations, summary reports for medical records alone would be delivered to clinicians. This idea has been accepted by some clinicians. To realize the revised system, we presently are planning to establish a method to display EEG on CRT.

Data Collection↗

[Effects of tachycardia on ischemic canine hearts during nitrous oxide-oxygen-halothane anesthesia].

Effects of tachycardia on left ventricular function, myocardial metabolism and intramyocardial pH under nitrous oxide-oxygen-halothane anesthesia, were studied in 11 canine hearts with critical coronary stenosis. A comparison was made with coronary occlusion. Critical stenosis was produced using a screw occluder to limit the left anterior descending coronary artery blood flow to prevent reactive hyperemia after 10 second occlusion. The degree of ischemia was estimated by intramyocardial pH, arterio-venous lactate and potassium. Intramyocardial pH was measured with a hydrogen ion-selective electrode implanted in the subendocardium. Tachycardia was induced by right cardiac sympathetic nerve stimulation. After 7 min tachycardia in dogs with coronary stenosis, intramyocardial pH decreased significantly from 7.09 +/- 0.10 to 6.83 +/- 0.15, then tended to return toward control levels over a period of 20 min after cessation of tachycardia, although some did not return to the control level even after 30 min. Regarding LV function, LVP and positive LV dp/dt max did not increase. Negative LV dp/dt max decreased significantly. The time constant (T) was prolonged but not significantly, while LVEDP rose considerably from 8.2 +/- 4.1 mmHg to 14.6 +/- 6.8 mmHg. In contrast, after 7 min occlusion, intramyocardial pH decreased significantly from 7.14 +/- 0.08 to 6.72 +/- 0.15 and recovered after 15 min. LVP decreased slightly. Positive and negative LV dp/dt max decreased significantly. T was not prolonged initially, but after reperfusion prolonged significantly. LVEDP increased significantly from 7.9 +/- 3.3 mmHg to 11.9 +/- 6.3 mmHg. In summary, tachycardia in dogs with coronary stenosis under nitrous oxide-oxygen-halothane anesthesia caused regional ischemia. The degree of ischemia was slightly less than with occlusion, but LV diastolic dysfunction was more prominent.

Anesthesia, Inhalation↗

[A case of cerebral arterial ectasia accompanied by intraventricular hemorrhage].

A case of cerebral arterial ectasia is reported. A sixty-one year old male revealed sudden disturbance of consciousness. CT examinations disclosed massive intraventricular hemorrhage and the cerebral angiograms showed remarkable elongation and dilatation of cerebral arteries. The authors discuss cerebral arterial ectasia from a clinico-pathological point of view.

Cerebral Arterial Diseases↗

Glomerular lesions in mice transgenic for growth hormone and insulinlike growth factor-I. I. Relationship between increased glomerular size and mesangial sclerosis.

The glomeruli of mice transgenic for bovine growth hormone (GH mice) were disproportionately enlarged as a function of either kidney or body weight. Glomerular size correlated with mesangial sclerosis and the urine albumin/creatinine ratio. The glomerular lesions consisted of mesangial proliferation (4 to 5 weeks) followed by progressive mesangial sclerosis (19 weeks), resulting in complete glomerulosclerosis at 30 to 37 weeks. Albuminuria paralleled the glomerulosclerosis. In contrast, mice transgenic for insulinlike growth factor-I (IGF-I mice) did not develop glomerulosclerosis, even though glomerular size significantly increased. Glomerular hypertrophy, however, did not reach that in GH mice. These data suggest that high levels of circulating GH lead to a disproportionate increase in glomerular cellularity and volume, as well as glomerulosclerosis. This does not appear to be the result of high levels of circulating IGF-I stimulated by GH, as the serum IGF-I level in GH mice was lower than that in IGF-I mice.

Albuminuria↗

A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization.

The functional, high affinity form of interleukin-2 receptor (IL-2R) is composed of two receptor components, the IL-2R alpha (p55) and IL-2R beta (p70-75) chains. Unlike the IL-2R alpha chain, the IL-2R beta chain contains a large cytoplasmic domain that shows no obvious tyrosine kinase motif. In the present study, we report the establishment of a system in which the cDNA-directed human IL-2R beta allows growth signal transduction in a mouse pro-B cell line. This system enabled us to identify a unique region within the cytoplasmic domain of the human IL-2R beta chain essential for ligand-mediated signal transduction. We also demonstrate that certain cytoplasmic deletion mutants in the IL-2R beta chain, although deficient in signal transduction, can still form high affinity IL-2R in conjunction with endogenous mouse IL-2R alpha chain; the mutants are still able to internalize the ligand as well.

Amino Acid Sequence↗

Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's.

Interleukin-2 (IL-2) binds to two distinct receptor molecules, the IL-2 receptor alpha (IL-2R alpha, p55) chain and the newly identified IL-2 receptor beta (IL-2R beta, p70-75) chain. The cDNA encoding the human IL-2R beta chain has now been isolated. The overall primary structure of the IL-2R beta chain shows no apparent homology to other known receptors. Unlike the IL-2R alpha chain, the IL-2R beta chain has a large cytoplasmic region in which a functional domain (or domains) mediating an intracellular signal transduction pathway (or pathways) may be embodied. The cDNA-encoded beta chain binds and internalizes IL-2 when expressed on T lymphoid cells but not fibroblast cells. Furthermore, the cDNA gives rise to the generation of high-affinity IL-2 receptor when co-expressed with the IL-2R alpha chain cDNA.

Amino Acid Sequence↗

Ligand-dependent selection of the receptor gene: segregation of IL-2 binding activity and anti-Tac reactivity by a single amino acid alteration in the Tac antigen (p55).

The Tac antigen (p55, CD25) is a 55 kDa glycoprotein that binds interleukin 2 at low affinity (Kd congruent to 10-50 nM). Expression of the Tac antigen is induced in the activated human T cells to constitute the functional, high-affinity IL-2 receptors (IL-2Rs) (Kd congruent to 10 pM) in conjunction with p70-75. A monoclonal antibody, anti-Tac, recognizes this molecule and inhibits the binding of IL-2 to both high- and low-affinity IL-2Rs. This observation indicates that IL-2 and anti-Tac binding sites are located close to each other within the Tac molecule. In this report, by utilizing a novel approach, we selected cDNAs encoding the Tac antigen variants whose reactivity with anti-Tac is greatly reduced, while retaining their IL-2 binding activity. Each of the mutant cDNAs contained a point (G----A) mutation resulting in an amino acid substitution at the particular amino-terminal portion of the Tac molecule (Asp-4). These results demonstrate that N-terminal amino acid Asp-4 is involved in the epitope recognized by anti-Tac, and that IL-2 binding site and anti-Tac binding site are structurally separable from each other in the Tac molecule.

Amino Acid Sequence↗

Human interleukin 2 (IL 2) receptor beta chain allows transduction of IL 2-induced proliferation signal(s) in a murine cell line.

Interleukin 2 (IL 2) delivers cell growth signal by virtue of its interaction with the high-affinity receptor complex, which consists of two distinct IL 2-binding molecules: the IL 2 receptor alpha (IL 2R alpha) and beta (IL 2R beta) chains. Unlike many known growth factor receptors, neither of the IL 2R chains seems to contain a tyrosine kinase domain. In this report, we have shown that the human IL 2R beta chain expressed in a murine IL 3-dependent, non-lymphoid cell line can transduce IL 2-induced cell proliferation signal(s) in combination with the autologous mouse IL 2R alpha chain. This observation should provide a tool to dissect IL 2-induced signal transduction pathway in lymphoid and non-lymphoid cells.

Animals↗

Transient induction of IL-2 receptor in cultured T cell lines by HTLV-1 LTR-linked tax-1 gene.

Human lymphotropic virus, HTLV-1, encodes in its proviral genome a transcriptional activator protein, tax-1, that may be responsible for the development of virus-induced adult T cell leukemia (ATL), possibly through the aberrant activation of the genes for interleukin-2 (IL-2) and one of its receptor (IL-2R) components, the IL-2 receptor alpha-chain (IL-2R alpha). In the present study, an expression plasmid containing tax-1 cDNA under the control of HTLV-1 LTR was introduced into mouse and human CD4-positive T cell lines. Analysis of the established cell clones revealed a number of interesting features: (i) a limited fraction of the total cell population (less than 25% in each clone) was positive for IL-2R alpha; (ii) the IL-2R alpha expression was not permanent, as the IL-2R alpha positive and negative cells could convert either way. The experimental data suggest that the observed heterogeneity in IL-2R alpha expression in the transformants is due to a cell-cycle-regulated expression and function of tax-1. Furthermore, a proportion of the induced IL-2R in EL-4 was in high-affinity form, suggesting the association of the IL-2R alpha and the IL-2R beta chain (p70-75) components.

Animals↗

Retroviral gp70 antigen in spontaneous mesangial glomerulonephritis of ddY mice.

We examined whether the retroviral envelope antigen, gp70, is a major nephritogenic antigen in ddY mice, a murine model of spontaneous mesangial glomerulonephritis associated with IgA and IgG deposition. Immunofluorescence microscopy revealed that the mesangial gp70 deposition increased with age in mice over 24 weeks old, as did the IgG and IgA deposits. Immunoelectron microscopy demonstrated the reaction products of gp70 superimposed on the electron dense deposits in the mesangial matrix. Various amounts of serum gp70 were detected in mice as young as 12 weeks without any apparent increase with age. There was no correlation between the serum level of gp70 and the extent of the glomerular gp70 deposition, whereas mice with heavier IgA deposition had higher mean levels of serum IgA. The absorption test demonstrated that significant amounts of serum gp70 composed immune complexes in 40 week-old ddY mice developing glomerulonephritis; however, this bound form of gp70 was not observed in 12 week-old mice without glomerulonephritis. Systemic examinations by immunofluorescence staining showed that gp70 was mainly localized in various lymphoid tissues. These findings suggest that the gp70 antigen, mostly derived from lymphoid cells, may circulate as immune complexes and accumulate in the mesangial area, thus contributing to the development of glomerulonephritis in these mice. In addition, the pathogenic role of the increased IgA production in these mice was discussed.

Animals↗

Structure of the functional interleukin-2 receptor. Evidence for the association of human p55 and murine p75 molecules in a mouse T cell line.

The structural basis of the high affinity interleukin-2 receptor which was previously reconstituted in a cultured murine T cell line, EL4 by expressing either wild-type Tac antigen complementary DNA (cDNA) or a chimeric cDNA was characterized. The chimeric cDNA encodes a membrane portion whose extracellular portion consists of that of Tac antigen whereas transmembrane and cytoplasmic portions consists of those the human insulin beta chain. The Tac antigen/anti-Tac antibody complex was treated by chemical crosslinking reagents, purified by goat anti-mouse immunoglobulin (Ig), and was analysed by SDS-PAGE. We here demonstrated the presence in mouse EL4 transfectants of a novel membrane protein which is closely associated with the products of transfected cDNAs in the absence of interleukin-2. The protein is 75 kDa in size and is detected in cells which express high affinity interleukin-2 receptor but not in cells which only express low affinity interleukin-2 receptor. The transmembrane region and the cytoplasmic region of Tac antigen is not necessary for the formation of the complex consisting of Tac antigen and 75 kDa molecule, indicating that a murine 75 kDa molecule associates with Tac antigen extra-cellularly.

Animals↗

Postnatal development of thiamine metabolism in rat brain.

The activities of thiamine diphosphatase (TDPase), thiamine triphosphatase (TTPase), and thiamine pyrophosphokinase and the contents of thiamine and its phosphate esters were determined in rat brain cortex, cerebellum, and liver from birth to adulthood. Microsomal TTPase activity in the cerebral cortex and cerebellum increased from birth to 3 weeks, whereas that in the liver did not change during postnatal development. Microsomal TDPase activity in the cerebral cortex showed a transient increase at 1-2 weeks, but that in the cerebellum did not change during development. In contrast to the activity of the brain enzyme, that of liver microsomal TDPase increased stepwise after birth. Thiamine pyrophosphokinase activity in the cerebellum increased from birth to 3 weeks and then decreased, whereas that in the cerebral cortex and liver showed less change during development. TDP and thiamine monophosphate (TMP) levels increased after birth and plateaued at 3 weeks whereas TTP and thiamine levels showed little change during development in the cerebral cortex and cerebellum. The contents of thiamine and its phosphate esters in the liver showed more complicated changes during development. It is concluded that thiamine metabolism in the brain changes during postnatal development in a different way from that in the liver and that the development of thiamine metabolism differs among brain regions.

Acid Anhydride Hydrolases↗

Immunoelectron microscopic localization of fibrin-related antigen in human glomerular diseases.

The distribution of fibrin-related antigen (FRA) in glomeruli was examined by immunoelectron microscopy in 9 patients with idiopathic membranous nephropathy (MN), 8 patients with minimal-change nephrotic syndrome, and 10 patients with IgA nephropathy (IgA-N), using antisera against human gamma--chain, alpha-chain, mu-chain, and fibrinogen. Electron-dense reaction products of FRA were observed in the endothelium, subendothelium, and/or in electron-dense deposits (EDD). Among the three glomerular diseases, the amount of electron-dense reaction products of FRA in the endothelium was highest in MN. This suggests that coagulation occurs on the endothelium in MN. Although the mesangial EDD of IgA-N were intensely stained with reaction products of FRA, the staining was weak in the subepithelial EDD of MN. This suggests that FRA hardly penetrates into the subepithelial EDD in MN.

Antigens↗

Ultrastructural distribution of von Willebrand factor in human glomerular diseases.

The distribution of the von Willebrand factor (vWF) as the factor-VIII-related antigen in glomeruli was examined by immunoelectron microscopy in 10 patients with idiopathic membranous nephropathy (MN), 8 patients with minimal-change nephrotic syndrome (MCNS), and 11 patients with IgA nephropathy (IgA-N). Electron-dense reaction products of vWF were observed in the endothelium and mesangium in all specimens examined. However, they were not detected in subepithelial electron-dense deposits of MN. The amount of electron-dense reaction products of vWF in the endothelium was significantly higher in MN than that in MCNS or IgA-N. This finding suggests that the glomerular endothelium in MN is the site of the local activation of coagulation and platelet aggregation system in glomerular capillary wall lesions.

Glomerulonephritis, IGA↗

Transforming growth factor-beta. Murine glomerular receptors and responses of isolated glomerular cells.

Proliferation of resident glomerular cells and the accumulation of mesangial matrix are histologic abnormalities which are observed in the course of many progressive glomerular diseases. We explored the potential regulatory effects of transforming growth factor-beta (TGF-beta) on these processes. We found that cultured mouse glomerular endothelial, mesangial, and epithelial cells as well as isolated intact rat glomeruli possess high-affinity receptors for TGF-beta. We also found that, although TGF-beta consistently inhibited the proliferation of glomerular endothelial and epithelial cells, it acted as a bifunctional regulator of mesangial cell proliferation. TGF-beta significantly increased the production of collagen and fibronectin by glomerular mesangial cells whereas only fibronectin production was augmented in glomerular epithelial cells. The presence of TGF-beta receptors on intact glomeruli and on each glomerular cell type and the demonstrated responsiveness of these cells to TGF-beta combine to suggest that potentially important interactions may occur between resident glomerular cells and TGF-beta in vivo.

Animals↗

Effect of vitamin B12 deficiency on S-adenosylmethionine metabolism in rats.

The effect of vitamin B12 (B12) deficiency on the levels of S-adenosylmethionine (SAM) in tissues and the activities of hepatic methionine synthase, methionine adenosyltransferase and glycine N-methyltransferase were investigated. The striking depression of methionine synthase activity was observed in all rats fed the B12-deficient diets with or without methionine supplementation for 150 days. The SAM level in liver was decreased by B12 deficiency. However, brain SAM level was not affected. The activities of hepatic methionine adenosyltransferase isozymes, alpha-form and beta-form, were decreased by B12 deficiency. Hepatic glycine N-methyltransferase activity in rats fed the low methionine-B12-deficient diet showed a tendency to lower, although the change the activity was not statistically significant, compared with B12-supplemented rats. It is proposed that the fall in the activity of hepatic methionine adenosyltransferase may be one of the causes of the decreased hepatic SAM level in B12-deficient rats.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗