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T Yoshimoto

Publications and source records attributed to T Yoshimoto.

At least 109 records · Page 6Linked to original sources
PubMed2000

Adrenocortical carcinoma manifesting pure primary aldosteronism: a case report and analysis of steroidogenic enzymes.

Adrenocortical carcinoma manifesting pure hyperaldosteronism is extremely rare. We report here a 61-year-old woman with biochemically proven primary aldosteronism due to right adrenocortical carcinoma. Computed tomographic scan showed 4.5x5.3 cm lobulated mass with tiny calcification, while there was no significant uptake of 131I-iodomethyl norcholesterol in the tumor. Immunohistochemical analysis demonstrated expression of steroidogenic enzymes in the tumor tissue: P-450scc, P-45c21, 3beta-hydroxysteroid dehydrogenase, P450(17alpha), and P-450(11beta). In addition, we could demonstrate mRNA expression of aldosterone synthase (P-450aldo:CYP11B2) in the tumor by specific ribonuclease protection assay. This is the first report of a case of primary aldosteronism due to adrenocortical carcinoma, in which expression of all sets of steroidogenic enzymes required for aldosterone synthesis was proven.

Adrenal Cortex Neoplasms↗
PubMed2000

Diffusion-weighted MRI and selection of patients for fibrinolytic therapy of acute cerebral ischaemia.

Treatment of patients with acute cerebral ischaemic events remains controversial. We investigated the reversibility of high signal intensity on diffusion-weighted (DW) MRI after acute local intra-arterial fibrinolysis (LIF) and the feasibility of DW MRI for selecting patients for acute LIF. Nine patients with acute middle cerebral artery embolic occlusion underwent single-photon emission computed tomography (SPECT) and DW MRI followed by acute LIF using tissue plasminogen activator. Recanalisation was observed in all patients, and eight improved clinically. The area of high signal intensity on pretreatment DW MRI was smaller than the low-uptake area on SPECT in all patients, and went on to infarction, as detected by MRI or CT 3 days after onset in all patients. It appears to correlate, at least clinically, with irreversible brain damage. Therefore, acute LIF should not be performed in patients with areas of high signal intensity in the cortex responsible for the symptoms. SPECT remains important, because areas normal on DW MRI with low uptake on SPECT often contribute to functional prognosis.

Acute Disease↗
PubMed2000

Systemic and cerebral haemodynamics during craniotomy under mild hypothermia in patients with acute subarachnoid haemorrhage.

BACKGROUND: Mild hypothermia provides cerebral protection against ischaemic insults in various animal models. We compared systemic and cerebral oxygenation between mild hypothermic and normothermic management in 60 patients with acute subarachnoid haemorrhage who underwent clipping of cerebral aneurysms. METHOD: The temperature in the pulmonary artery was maintained at 36 degrees C in 28 patients and was reduced to 34 degrees C in 32 patients. Parameters in the systemic and cerebral haemodynamics from pulmonary artery and internal jugular vein catheters were compared between the two groups immediately after the induction of anaesthesia (TI). and just before temporary occlusion or aneurysm clipping (T2). FINDINGS: Cardiac index, oxygen delivery index, oxygen consumption index, and oxygen saturation of the jugular bulb were significantly lower at T2 in hypothermic group (H) (2.9 +/- 0.6 L/min/m2, 400.8 +/- 106.3 ml/min x m2, 87.0 +/- 14.8 ml/min x m2, 55.2 +/- 6.6%, respectively) than normothermic group (N) (3.7 +/- 0.6, 521.0 +/- 105.5, 109.9 +/- 21.7, 60.9 +/- 6.6) (p < 0.05). The arterial lactate and arteriojugular difference in oxygen content were significantly higher in H (2.3 +/- 1.3 mmol/L, 6.5 +/- 1.5 ml/dl, respectively) than in N (1.7 +/- 1.0, 5.6 +/- 1.2) (p < 0.05). Arteriojugular differences in carbon dioxide tension and hydrogen ion content were significantly lower at T2 in H (-10.8 +/- 2.1 mm Hg, -6.4 +/- 1.3 nmol/L, respectively) than in N (-8.9 +/- 2.8, -5.3 +/- 1.0) (p < 0.05). INTERPRETATION: The balance between oxygen supply and demand systemically and in the brain may worsen during aneurysm surgery for patients with acute subarachnoid haemorrhage under mild hypothermia. Oxygenation of the brain and the whole body should be monitored closely during this surgery, and adequate circulatory assistance is recommended under mild hypothermia.

Acute Disease↗
PubMed2000

Combined neuroendovascular stenting and coil embolization for cervical carotid artery dissection causing symptomatic mass effect.

BACKGROUND: Carotid artery dissection manifesting with symptomatic mass effect has been treated surgically according to the previous literature. Recently, some cases of carotid artery dissection manifesting with ischemic symptoms were treated successfully with endovascular insertion of coils after stenting. METHODS: A 42-year-old man with spontaneous dissection of the left cervical internal carotid artery (ICA) presented with the major complaint of left neck swelling and pain that was considered to be the mass effect of a pseudoaneurysm caused by dissection of the ICA. Endovascular therapy using a stent and coils was performed. The self-expanding stent was deployed to cover the neck of the pseudoaneurysm. A microcatheter was then guided through the stent mesh into the aneurysm, and coils were placed to pack it. RESULTS: Four months later, angiography revealed complete embolization of the aneurysm with preserved flow in the ICA. The mass effect attributable to the pseudoaneurysm was relieved symptomatically as well as radiologically. CONCLUSION: Cervical artery dissection with symptomatic mass effect++ can be treated successfully by the combination of stent and coils. This may be considered as an alternative to conventional proximal ligation, extracranial-intracranial bypass, or direct surgical repair.

Adult↗
PubMed2000

Postoperative hyperperfusion syndrome in elderly patients with chronic subdural hematoma.

BACKGROUND: Temporary acute agitated delirium is a frequent complication after surgery for chronic subdural hematoma (CSH) in elderly patients. To clarify the pathogenic mechanism underlying this complication, we measured cerebral blood flow before and after surgery in elderly patients with CSHs. METHODS: Twenty-seven patients aged 75 years or older with unilateral CSH underwent treatment involving a single burr hole craniostomy with continuous catheter drainage. Cerebral blood flow was measured using single photon emission computed tomography 1 day before surgery, and at 1 hour and 24 hours after surgery. Acute agitated delirium was diagnosed by the characteristic behavioral abnormality. RESULTS: SPECT imaging 1 hour after surgery demonstrated hyperperfusion in the cerebral cortex beneath the CSH in 14 patients (51.9%). Of these 14 patients, five showed acute agitated delirium a few hours after surgery that persisted for 10 to 12 hours. A hematoma was detected in the right hemisphere in all five patients. Hyperperfusion was significantly more intense in patients with acute agitated delirium both 1 hour and 24 hours after surgery than in patients (n = 9) without acute agitated delirium. Moreover, mean arterial blood pressure during the first postoperative hour was significantly higher in patients with acute agitated delirium. CONCLUSION: In elderly patients with CSH, intense and prolonged hyperperfusion after surgery induces temporary acute agitated delirium. This postoperative hyperperfusion syndrome is exacerbated by hypertension.

Aged↗
PubMed2000

Modulated vasodilator responses to natriuretic peptides in rats exposed to chronic hypoxia.

Natriuretic peptides (NPs), such as atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), and adrenomedullin (ADM), are endogenous vasodilators acting via specific receptors. This study addressed the question of how pulmonary artery (PA) responses to these peptides and the gene expression of their receptors are modulated in pulmonary hypertension rat models exposed to chronic hypoxia. In this study, isometric tension was measured in PA rings exposed to these NPs and 8-bromoguanosine 3', 5'-cyclic monophosphate (8-bromo-cGMP). It was compared with messenger ribonucleic acid (mRNA) levels of NP-A and -B receptors, which bind to ANP and CNP, respectively, as determined by ribonuclease (RNase) protection assay. Chronic hypoxia increased the maximal relaxation elicited by ANP, but the responses to CNP and 8-bromo-cGMP were unchanged. Chronic hypoxia did not change NP-A and -B receptor mRNA levels. The results showed that pulmonary artery response to atrial natriuretic peptide is selectively enhanced, possibly via a post-transcriptional modulation of its receptor in chronically hypoxia rats. These pharmacological characteristics of atrial natriuretic peptide are consistent with the hypothesis that the atrial natriuretic peptide system is protective against the progression of pulmonary hypertension.

Adrenomedullin↗
PubMed2000

IL-18 induction of IgE: dependence on CD4+ T cells, IL-4 and STAT6.

Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (TH2) cytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in allergic disorders. Although it is known that IL-4 is critical to the polarization of naïve CD4+ T cells to a TH2 phenotype, both in vitro and in many in vivo systems, other factors that regulate in vivo IL-4 production and TH2 commitment are poorly understood. IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to become active, was found to increase IgE production in a CD4+ T cells-, IL-4- and STAT6-dependent fashion. IL-18 and T cell receptor-mediated stimulation could induce naïve CD4+ T cells to develop into IL-4-producing cells in vitro. Thus, caspase-1 and IL-18 may be critical in regulation of IgE production in vivo, providing a potential therapeutic target for allergic disorders.

Animals↗
PubMed2000

A pivotal role of cell-bound but not soluble CD4 molecules in full development of lupus-like manifestations in MRL-Fas(lprcg)/Fas(lprcg) mice.

The role of CD4 molecules in the autoimmune and lymphoproliferative syndrome caused by murine Fas mutations was studied using the novel systemic lupus erythematosus (SLE) model, MRL-Fas(lpr(cg))/Fas(lprcg) (MRL-lpr(cg)) mice, in combination with the novel mutant CD4 gene producing soluble CD4 (sCD4) instead of membrane-bound CD4 (mCD4). For this purpose, various autoimmune manifestations were compared among MRL-lpr(cg) mice homozygous (CD4slprcg), heterozygous (CD4s/mlpr(cg)), and wild-type (CD4mlpr(cg)) for the CD4 mutation. The mortality, glomerulonephritis, proteinuria, and lymphadenopathy were significantly ameliorated in CD4slprcg compared with CD4mlpr(cg) and CD4s/mlpr(cg) mice, both being comparable in these clinical characteristics. In parallel with the clinical improvement, the serum levels of immunoglobulin, anti-DNA antibodies, anti-nuclear antibodies and immune complexes, and the extent of glomerular immune deposition, were significantly lower in the former. The results indicate that mCD4 is important and can not be replaced by sCD4 in full development of SLE-like manifestations, and suggest that CD4+ T cells may aggravate the autoimmune disease by stimulating autoreactive B cells to produce autoantibodies through their helper activity in Fas mutant models. The sCD4 levels in the serum and spleen elevated with the increased accumulation of B220+CD4-CD8- (double-negative (DN)) T cells in CD4slpr(cg) mice. This, together with the significantly milder lymphadenopathy associated with lower DN T cell contents in CD4slpr(cg) than CD4mlpr(cg) mice, implies that some of abnormal DN T cells may be derived from cells of the CD4 lineage.

Animals↗
PubMed2000

Impaired delayed-type hypersensitivity response in mutant mice secreting soluble CD4 without expression of membrane-bound CD4.

Delayed-type hypersensitivity (DTH) is an important in vivo manifestation of cell-mediated immunity. We examined the DTH response to methylated bovine serum albumin of a novel mutant strain of mice that have soluble CD4 (sCD4) in their circulation without expression of CD4 on the cell surface. The DTH response of the mutant mice was severely impaired, although the response of CD4 knockout (KO) mice, generated by homologous recombination, was comparable to that of wild-type mice. The response of the mutant mice was restored by the neutralization of sCD4 with anti-CD4, and that of CD4KO mice was markedly reduced by the implantation of a diffusion chamber containing sCD4 cDNA transfectant cells. The restored DTH response of the mutant mice treated with anti-CD4 was abolished by treatment with anti-interferon-gamma (IFN-gamma). IFN-gamma production by CD4 mutant and CD4KO mice was consistent with their DTH response and inversely related to the presence of sCD4 in their circulation, indicating that sCD4 impairs the DTH response by blocking the production of IFN-gamma in our mutant mice. These results raise the possibility that sCD4 could impair cell-mediated immunity. Our mutant mice would provide a useful tool with which to analyse the mechanisms of the DTH reaction.

Animals↗
PubMed2000

Distribution of c-fos mRNA in the brain following intracerebroventricular injection of nitric oxide (NO)-releasing compounds: possible role of NO in central cardiovascular regulation.

We injected nitric oxide (NO)-releasing compounds and NO synthase (NOS) inhibitors into the brains of conscious, freely moving rats and measured the effects on mean arterial blood pressure (MAP) and heart rate, as well as on the expression of c-fos mRNA, neuronal NOS (nNOS) mRNA and NADPH-diaphorase, an indicator of NOS activity. When administered i.c.v., the NO donor, NOC-18, caused a significant fall in MAP and heart rate, whereas the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), induced a significant rise in MAP. The same dose of NOC-18 or L-NAME when administered i.v. did not affect MAP and heart rate. Centrally administered NOC-18 induced c-fos mRNA expression in several regions of the brain involved in the baroreceptor response, including the nucleus of the solitary tract, the area postrema and the rostral ventrolateral medulla, as well as areas involved in the integration of autonomic, neuroendocrine and behavioural responses, including the medial preoptic area, the organum vasculosum lamina terminalis, the bed nucleus of stria terminalis, the paraventricular nucleus (PVN), the supraoptic nucleus (SON), the central nucleus of amygdala (CeA) and the locus coeruleus. Most of the areas that expressed c-fos also contained nNOS mRNA and/or NADPH-d-positive neurones and fibres. i.c.v. injection of L-NAME induced c-fos mRNA expression in PVN, SON, locus coeruleus and NTS, suggesting a tonic inhibition of neuronal activity by NO or stimulation of neuronal activity by endogenous NO. i.v. injection of NOC-18 or L-NAME did not induce any significant c-fos mRNA expression in rat brain. These results demonstrate that NO acts directly in the brain to reduce the systemic blood pressure, and that the endogenous NO pathway may play a role in cardiovascular and autonomic regulation by modulating neuronal activities in discrete regions of the brain.

Amygdala↗
PubMed2000

Endovascular treatment of aneurysms associated with cerebral arteriovenous malformations: experiences after the introduction of Guglielmi detachable coils.

The authors have treated 172 patients with arteriovenous malformation (AVM) since 1993. Among them, 25 patients had aneurysms with a total number of 43. The aneurysms were divided into four groups; proper feeder aneurysm (4), flow-related distal aneurysm (beyond the circle of Willis or M1, 7), flow-related proximal aneurysm (26) and remote aneurysm (6). Guglielmi detachable coil (GDC) embolisation was performed in 12 patients with 15 aneurysms. Gamma knife radiosurgery for AVM was performed in 10 of those 12 patients. Two of the proper feeder aneurysms were embolised with liquid material, together with the corresponding part of the AVM. The other aneurysms were treated surgically (14) or observed (12). There was no bleeding from aneurysms after treatment. In conclusion, GDC embolisation is a useful treatment for aneurysms associated with AVM, especially if the AVM is treated by radiosurgery. Liquid embolisation of a proper feeder aneurysm is one of the treatment options. Ltd.

Adult↗
PubMed2000

Alleviation of renal disease and lymphadenopathy in MRL-Fasp(lrcg)/Fas(lprcg) (MR-lpr(cg)) mice neonatally infected with mouse mammary tumor virus encoding superantigen strongly reactive with TCR Vbeta8.2 element.

Mouse mammary tumor virus transmitted by FM mice (FM-MMTV) encodes a superantigen (SAg) characterized by strong reactivity with TCR Vbeta8.2 element and broad spectrum of Vbeta reactivity. To investigate what effects the expression in vivo of FM-MMTV SAg exhibits on the course of the disease in a lupus-prone model, MRL/MpJ-Fas(lprcg)/Fas(lprcg) (MRL-lpr9cg) mice, neonatally FM-MMTV-infected MRL-lprcg(MMTV) and uninfected MRL-lpr(cg) mice were compared for various disease parameters. In MRL-lprcg(MMTV), survival was significantly prolonged, glomerulonephritis, proteinuria, and lymphadenopathy were clearly ameliorated, and the production of serum immunoglobulin G (IgG), complement-activating IgG2a, and cryogenic IgG3 autoantibodies, which are thought to be pathogenic to kidneys, and circulating immune complexes (IC), and glomerular IC deposition were significantly suppressed. FM-MMTV infection deleted Vbeta8.2+ cells by about 90% and Vbeta14+ cells less efficiently in all of the CD4+, CD8+, and B220+ CD4- CD8- or double-negative (DN) T-cell populations, and Vbeta8.1+ cells in the CD4+ population but not in the others. Similar deletion profiles of CD8+ and DN T cells support that DN T cells are derived from the CD8 lineage. The results imply that the specific regulation of the immune system with viral SAg has a potential for development of an attractive immunomodulatory therapy of autoimmune diseases.

Animals↗
PubMed2000

IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells.

IL-18 is a proinflammatory cytokine that plays an important role in NK cell activation and T(h)1 response. IL-18 has a structural homology to IL-1, particularly IL-1beta. IL-18R, composed of IL-1R-related protein (IL-18Ralpha) and IL-1R accessory protein-like (IL-18Rbeta), belongs to the IL-1R family. Furthermore, IL-18R at least partly shares the signal transducing system with IL-1R. Thus, the IL-18-IL-18R system has a striking similarity to the IL-1-IL-1R system. For this reason, we regarded it important to investigate whether, like IL-18, IL-1beta synergizes with IL-12 in inducing IFN-gamma production from human T cells and plays an important role in the T(h)1 response. Here we show that IL-12 and IL-1beta synergistically induce T cells to proliferate and produce IFN-gamma without their TCR engagement. IL-12 stimulation induced an increase in the proportion of T cells positive for IL-18R. Then, IL-12-stimulated T cells responded to IL-18 or IL-1beta by their proliferation and IFN-gamma production, although levels of IL-1beta-induced responses were lower. CD4(+)CD45RA(+) T cells, although they constitutively expressed IL-18Rbeta mRNA, did not express IL-18Ralpha mRNA. Phytohemagglutinin (PHA) stimulation alone induced IL-18Ralpha mRNA without affecting the expression of IL-18Rbeta mRNA. T(h)1-inducing conditions (PHA, IL-12 and anti-IL-4) further increased this expression. We also show that T(h)1 cells but not T(h)2 cells have increased expression of IL-18R and IL-1R, and produce IFN-gamma in response to IL-18 and/or IL-1beta.

Drug Synergism↗
PubMed2000

Suppression of prostaglandin E(2)-mediated c-fos mRNA induction by interleukin-4 in murine macrophages.

When murine peritoneal macrophages were stimulated for 30 min with arachidonic acid, the growth-associated immediate early gene c-fos was induced in a concentration-dependent manner as assessed by Northern blot analysis. The arachidonic acid-induced c-fos mRNA expression was inhibited by a cyclooxygenase inhibitor, indomethacin, but not by a lipoxygenase inhibitor, nordihydroguaiaretic acid. Macrophages produced prostaglandin (PG) E(2) from arachidonic acid as determined by an enzyme immunoassay. Northern blot analysis revealed the expression of PGE receptor EP2 and EP4 subtypes, but not EP1 and EP3 in murine macrophages. PGE(2) brought about a marked elevation of cAMP, and c-fos mRNA expression was increased by PGE(2) and dibutyryl cAMP in these cells. These results suggest that arachidonic acid is transformed to PGE(2), which then binds to EP2 and EP4 receptors to increase intracellular cAMP and c-fos mRNA expression. Furthermore, the induction of c-fos by arachidonic acid, PGE(2), and cAMP was suppressed by pretreatment with interleukin (IL)-4. We also showed that the tyrosine phosphorylation of a Janus kinase, JAK3, is enhanced by IL-4 treatment, suggesting that the PGE(2)-mediated c-fos mRNA induction is inhibited by IL-4 through the tyrosine phosphorylation of JAK3.

3T3 Cells↗
PubMed2000

Glutamate 83 is important for stabilization of domain-domain conformation of Thermus aquaticus glycerol kinase.

The gene glpK, encoding glycerol kinase (GlpK) of Thermus aquaticus, has recently been identified. The protein encoded by glpK was found to have an unusually high identity of 81% with the sequence of GlpK from Bacillus subtilis. Three residues (Arg-82, Glu-83, and Asp-244) of T. aquaticus GlpK are conserved in all the known GlpK sequences, including those from various bacteria, yeast and human. The roles that these three residues play in the catalytic mechanism were investigated by using site-directed mutagenesis to produce three mutants: Arg-82-Ala, Glu-83-Ala, and Asp-244-Ala. Replacement of Asp-244 by Ala resulted in a complete loss of activity, thus suggesting that Asp-244 is important for catalysis. Taking k(cat)/K(m) as a simple measure of catalytic efficiency, the mutants Arg-82-Ala and Glu-83-Ala were judged to cause 190- and 37,000-fold decrease, respectively, when compared to the wild-type GlpK. Thus, these three residues play a critical role in the catalytic mechanism. However, only mutant Glu-83-Ala was cleaved by alpha-chymotrypsin, and proteolysis studies showed that the mutant Glu-83-Ala involves a change in the exposure of Tyr-331 at the alpha-chymotrypsin site. This indicates a large domain conformational change, since the residues corresponding to Glu-83 and Tyr-331 in the Escherichia coli GlpK sequence are located in domain IB and domain IIB, respectively. The apparent conformational change caused by replacement of Glu-83 leads us to propose that Glu-83 is an important residue for stabilization of domain conformation.

Amino Acid Substitution↗