Search PubMed⌕ Search

Biomedical subjects

Y Ueda

Publications and source records attributed to Y Ueda.

At least 289 records · Page 16Linked to original sources

ESR spectroscopy for analysis of hippocampal elimination of a nitroxide radical during kainic acid-induced seizure in rats.

To analyze the balance between free radical production and elimination during seizure, techniques were developed to monitor the sequential changes in the level of an exogenous free radical by ESR in the brains of freely moving rats given kainic acid (KA) to induce seizures (n = 6) and control rats given saline (n = 6). The hippocampus of each rat was perfused with a nitroxide radical solution for 120 min by in vivo microdialysis. Then an intraperitoneal injection of KA or the physiological saline was given to each rat, and the perfusate was changed to Ringer's solution. ESR analysis of sequential samples of dialysate taken after injection revealed an exponential decay in signal amplitude. The median half-life of the nitroxide radical was significantly longer in the KA-treated group than in the control group (P < 0.01). This finding demonstrates a decreased capacity of the hippocampus to eliminate the nitroxide radical from the extracellular space during seizure and may help clarify the mechanism of neuronal cell vulnerability to free radicals during insult or degeneration.

Animals↗

Amygdalar injection of FeCl3 causes spontaneous recurrent seizures.

Rats were microinjected with a 100 mM aqueous solution of ferric chloride into the left amygdaloid body. Behavior was observed and depth electroencephalograms were recorded over the 30 days following injection. All of the FeCl3-injected rats developed isolated epileptiform discharges from the ipsilateral amygdala soon after injection. Within 5 days epileptiform discharges were arising as well from the contralateral amygdala and behavioral seizures were observed. These spontaneous seizures occurred in a pattern associated with stage 4 kindling, with rearing and bilateral forelimb clonus. Seizures persisted during the 30 days of the experiment. Recording from chronically implanted depth electrodes showed development of spike discharges, with recurrent seizures arising from amygdalar regions with propagation into both hippocampi. Aqueous iron is known to initiate lipid peroxidation by free radical mechanisms. Our observations suggest that epileptogenesis followed by chronic, spontaneous seizures could be initiated by deposition of iron-containing compounds into limbic structures of the rat.

Amygdala↗

Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium.

Since angiotensin-converting enzyme (ACE) produces angiotensin II in the heart, ACE inhibitors may prevent coronary vasoconstriction and increase coronary blood flow. On the other hand, since ACE inhibitors also inhibit kininase II which results in reduced degradation of bradykinin, ACE inhibitors may increase cardiac nitric oxide (NO) levels via stimulation of bradykinin receptors. This study was undertaken to test whether ACE inhibitors increase the cardiac NO levels and coronary blood flow in the ischemic myocardium. In 34 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. When either imidaprilat or cilazaprilat of 3 microg/kg/min was infused into the bypass tube for 10 min after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 31 +/- 1 to either 45 +/- 5 or 43 +/- 4 ml/100 g/min despite no changes in coronary perfusion pressure (43 +/- 2 mmHg). During an infusion of either imidaprilat or cilazaprilat, bradykinin and the end-products of NO (nitrate + nitrite) concentrations of coronary venous blood were markedly increased, which were attenuated by either HOE-140 (an inhibitor of bradykinin receptors) or by N(omega)-nitro-L-arginine methyl ester (an inhibitor of NO synthase). We also observed increases in cardiac bradykinin and NO levels due to either imidaprilat or cilazaprilat in the low constant coronary blood flow condition. It is concluded that ACE inhibitors can increase cardiac NO levels via the accumulation of bradykinin in the ischemic myocardium.

Angiotensin-Converting Enzyme Inhibitors↗

A case report of immunotherapy on a patient with advanced gastric cancer by adoptive transfer of OK-432-reactive HLA-matched allogeneic lymphocytes.

Adoptive immunotherapy (AIT) for non-hematological malignancies, using HLA-matched donor lymphocytes, has been rarely reported. For a 35-year-old male patient with peritoneal disseminated advanced gastric cancer, we performed AIT using lymphocytes from his HLA-matched 37-year-old brother and a streptococcal preparation, OK-432, as an antigen. After the donor had been immunized by intradermal administration of OK-432, OK-432-reactive lymphocytes were induced in vitro and transferred to the patient intravenously with OK-432. Low-dose systemic immunochemotherapy, using interleukin-2, 5-fluorouracil and cyclophosphamide, was concurrently administered with AIT. As a result, the Schnitzler metastasis in the patient reduced in size without any significant graft-versus-host-related complications. One of the effector mechanisms of therapeutic benefit was suggested to be cytokine release from the transferred OK-432-reactive lymphocytes. Our findings suggest the safety and efficacy of AIT using lymphocytes from an HLA-matched sibling and OK-432 as an antigen. Further studies to investigate the use of tumor-associated antigen and an HLA-matched sibling's lymphocytes for AIT of advanced cancer are warranted.

Adenocarcinoma, Scirrhous↗

Islet-cell hyperplasia causing hyperinsulinemic hypoglycemia in an adult.

We report a patient, a 23-year-old man, who had clinical and laboratory findings suggestive of insulinoma. Although imaging studies did not reveal any tumors in the pancreas, distal pancreatectomy was performed because the possibility of small insulinoma could not be completely excluded. Grossly, the surgically removed pancreas did not reveal any tumors. Microscopically, the pancreas exhibited islet cell hyperplasia and nesidioblastosis. To our knowledge, this is the first authentic reported case of islet-cell hyperplasia occurring in a Japanese adult.

Adult↗

Two-stage repair for aortic regurgitation with interrupted aortic arch.

We performed two-stage repair for a rare adult case of interrupted aortic arch with aortic regurgitation and sinus of Valsalva aneurysm. A lateroisthmic bypass was established with minimal thoracotomy and partial clamping of the descending aorta to preserve collateral circulation. This was followed by aortic root reconstruction with a prosthetic graft and valve for aortic regurgitation with sinus of Valsalva aneurysm. This less invasive two-stage repair for such a rare pathology may facilitate smooth recovery of the patient.

Adult↗

Laparoscopic splenopexy for pediatric wandering spleen.

Wandering spleen is an uncommon condition, showing a splenic hypermobility that results from laxity or maldevelopment of its suspensory ligament. This condition results in constant danger of splenic torsion and infarction. Wandering spleen was diagnosed in a 2-year-old girl who complained of intermittent abdominal pain, and viability of the spleen was confirmed by doppler ultrasound scan. Elective laparoscopic splenopexy was performed by anchoring the spleen wrapped in absorbable mesh. To our knowledge, this is the first reported case of laparoscopic splenopexy for wandering spleen. The authors believe that this approach is a safe and effective procedure for wandering spleen with the advantage of minimally invasive surgery.

Child, Preschool↗

Median raphe (parameatal) cysts of the penis.

PURPOSE: Although median raphe cysts of the penis have been widely reported the pathogenesis is obscure. We describe the microstructural detection of 3 cases of median raphe to study the true pathogenesis. MATERIALS AND METHODS: Three patients presented to our clinic of plastic surgery complaining of abnormal shape of the penis or mass recurrence. High magnification light microscopy and electron microscopy were performed. RESULTS: Microstructural study revealed that all 3 cases had similar findings to those of the common urethral mucosa. CONCLUSIONS: Median raphe cysts are derived from the external paraurethral ducts and contain features that to our knowledge have not been previously reported.

Adolescent↗

Significance of chromosomal alterations and mutations of the N-RAS and TP53 genes in relation to leukemogenesis of acute myeloid leukemia.

We examined chromosomes and mutations of the N-RAS and TP53 genes in 73 patients with acute myeloid leukemia (AML). Twenty-six patients showed a reciprocal chromosomal translocation or an inversion, and 34 patients showed only unbalanced aberrations. Balanced aberrations were predominantly detected in the AML patients who did not have myelodysplasia, preceding myelodysplastic syndrome, and a history of chemotherapy or radiation therapy. In contrast, unbalanced aberrations were more frequently seen in the patients with AML with trilineage myelodysplasia, AML transformed from MDS, and therapy-related AML. Twenty-two mutations of the N-RAS and TP53 genes were detected, and these mutations were frequently associated with unbalanced chromosomal aberrations. Furthermore, the spectrum of mutations was suggestive of an exposure to alkylating chemicals.

Acute Disease↗

Glutamate receptors: brain function and signal transduction.

Glutamate receptors are important in neural plasticity, neural development and neurodegeneration. N-methyl-d-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors act as glutamate-gated cation channels, whereas metabotropic receptors (mGluRs) modulate the production of second messengers via G proteins. Molecular studies from our and other laboratories indicated that NMDA receptors and mGluRs exist as multiple subunits (NMDAR1 and NMDAR2A-2D) and multiple subtypes (mGluR1-mGluR8). In light of the molecular diversity of glutamate receptors, we explored the function and intracellular signaling mechanisms of different members of glutamate receptors. In the visual system, retinal bipolar cells receive glutamate transmission from photoreceptors and contribute to segregating visual signals into ON and OFF pathways. The molecularly cloned mGluR6 is restrictedly expressed at the postsynaptic site of ON-bipolar cells in both rod and cone systems. Gene targeting of mGluR6 results in a loss of ON responses without changing OFF responses and severely impairs detecting visual contrasts. Since AMPA receptors mediate OFF responses in OFF-bipolar cells, two distinct types of glutamate receptors effectively operate for ON and OFF responses. mGluR1 and mGluR5 are both coupled to inositol triphosphate (IP3)/calcium signal transduction with an identical agonist selectivity. Single-cell intracellular calcium ([Ca2+]i) recordings indicated that glutamate evokes a non-oscillatory and oscillatory [Ca2+]i response in mGluR1-expressing and mGluR5-expressing cells, respectively. This difference results from a single amino acid substitution, aspartate of mGluR1 or threonine of mGluR5, at the G protein-interacting carboxy-terminal domains. Protein kinase C phosphorylation of the threonine of mGluR5 is responsible for inducing [Ca2+]i oscillations in mGluR5-expressing cells and cultured glial cells. Thus, the two closely related mGluR subtypes mediate diverging intracellular signaling in glutamate transmission.

Animals↗

A case of leptomeningeal metastasis from lung adenocarcinoma diagnosed by reverse transcriptase-polymerase chain reaction for carcinoembryonic antigen.

A case of leptomeningeal metastasis from lung adenocarcinoma is reported. In this case, we evaluated the feasibility of reverse transcriptased polymerase chain reaction (RT-PCR) methods to detect cancer cells in cerebrospinal fluids (CSF). Messenger RNA of carcinoembryonic antigen (CEA) was clearly demonstrated in CSF by reverse RT-PCR methods. An immunohistochemical study also demonstrated that tumor cells were stained positive with anti-CEA antibody. This case suggests that RT-PCR for CEA was a sensitive and useful method to diagnose leptomeningeal metastasis from lung adenocarcinoma.

Adenocarcinoma↗

Immunization with the "immunogenic peptide" of TSH receptor induces oligoclonal antibodies with various biological activities.

Balb/c mice were immunized with a synthetic peptide (P354-14) corresponding to "the immunogenic peptide" of human thyrotropin receptor (hTSH-R). Through screening for binding to the peptide, we obtained several monoclonal antibodies with various biological activities: thyroid stimulation (SAb), inhibition of TSH stimulation (BAb) and no significant effect on cAMP production. One of the stimulatory clones was further studied. This clone enhanced cAMP production in Cos-7 cells transformed with the truncated TSH-R cDNA deleting the immunogenic peptide. These results indicated that the immunogenic peptide of the TSH-R induces oligoclonal anti-TSH-R antibodies, although the region is not essential for the functional epitope.

Animals↗

Severe heat stroke associated with high plasma levels of plasminogen activator inhibitor 1.

In a 38-year-old man, severe heat stroke caused disseminated intravascular coagulation (DIC) associated with significantly elevated plasma plasminogen activator inhibitor 1 levels. Investigation of the effects of hyperthermia on coagulation and fibrinolysis showed, in apparent conflict with previous reports, a time lag between the initial hypercoagulable and hyperfibrinolytic response (within 24 hr) and hypofibrinolysis shown by a disproportionate increase of PAI-1 (after 24 h), which possibly occurs in correspondence with the recovery of vascular endothelial integrity. The patient was discharged without sequelae although computed tomography (CT) scans indicated the likelihood of venous infarction or posterior inferior cerebellar artery area infarction secondary to DIC.

Adult↗

Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique.

OBJECTIVES: The purpose of this study was to evaluate whether transthoracic Doppler echocardiography (TTDE) can reliably measure coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) in the clinical setting. BACKGROUND: Coronary flow velocity measurement has provided useful clinical and physiologic information. Advancement in TTDE provides noninvasive measurement of CFV and CFVR in the distal LAD. METHODS: In 23 patients, CFV in the distal LAD was measured by TTDE (5 or 3.5 MHz) under the guidance of color Doppler flow mapping at the time of Doppler guide wire (DGW) examination. Coronary flow velocity in the distal LAD were measured at baseline and hyperemic conditions (intravenous administration of adenosine 0.14 mg/kg/min) by both TTDE and DGW techniques. Coronary flow velocity reserve was defined as the ratio of peak hyperemic to basal averaged peak velocity in the distal LAD. RESULTS: Clear envelopes of basal and hyperemic CFV in the distal LAD were obtained in 18 (78%) of 23 study patients by TTDE. There were excellent correlations between TTDE and DGW methods for the measurements of CFV (averaged peak velocity: r=0.97, y=0.94x + 0.40; averaged diastolic peak velocity: r=0.97, y=0.94x + 0.69; systolic peak velocities: r=0.97, y=0.91x + 0.87; diastolic peak velocity: r=0.98, y=0.95x + 1.10). Coronary flow velocity reserve from TTDE correlated highly with those from DGW examinations (r=0.94, y=0.95x + 0.21). CONCLUSIONS: Noninvasive measurement of CFV and CFVR in the distal LAD using TTDE accurately reflects invasive measurement of CFV and CFVR by DGW method.

Adenosine↗

Restricted coronary flow reserve in patients with mitral regurgitation improves after mitral reconstructive surgery.

OBJECTIVES: The purpose of this study was to assess coronary flow characteristics in patients with chronic mitral regurgitation (MR). BACKGROUND: Coronary flow reserve (CFR) has been reported to be restricted in cases with left ventricular (LV) volume overload caused by aortic regurgitation and increased LV preload. METHODS: The study populations consisted of 31 patients with nonrheumatic chronic MR. Eleven with chest pain and normal coronary arteries served as control subjects. Phasic coronary flow velocities were obtained in the proximal segment of the angiographically normal left anterior descending coronary artery at rest and during hyperemia (0.14 mg/kg/min adenosine infusion intravenously) using a 0.014-in. (0.036 cm), 15-MHz Doppler guide wire. Coronary flow reserve was obtained from the ratio of hyperemic/baseline time-averaged peak velocity (APV). Thirteen cases who underwent mitral valve reconstructive surgery were also studied 1 month after surgery. RESULTS: Compared with control subjects, CFR was significantly reduced in cases with MR (2.1+/-0.5 vs. 33+/-0.6, respectively, p < 0.01) because baseline APV was significantly greater (28+/-8 vs. 19+/-6 cm/s, respectively, p < 0.01), although maximal hyperemic APV was not significantly different (56+/-14 vs. 61+/-16 cm/s, respectively, p = NS). Significant correlations were obtained between CFR and LV end-diastolic pressure (LVEDP) (r = 0.70, p < 0.01), LV mass index (r = 0.42, p < 0.01), LV end-diastolic volume (r = 038, p = 0.04) and MR volume (r = 0.39, p = 0.03), and stepwise regression analysis showed LVEDP was the most important determinant of CFR in MR (r2 = 0.49, p < 0.0001). This restricted CFR improved significantly after mitral valve reconstructive surgery (2.1+/-0.5 vs. 3.1+/-0.6, respectively, p < 0.01) because of reduction of baseline APV (28+/-8 vs. 21+/-8 cm/s, respectively, p < 0.01). CONCLUSIONS: Coronary flow reserve is limited in cases with MR because of elevation of baseline resting flow velocity. This reduction of CFR correlates well with increase in LV preload, mass and volume overload, especially with increase in LV preload, and this restricted CFR improves after mitral valve surgery.

Adult↗

In vivo analysis of hydrogen peroxide and lipid radicals in the striatum of rats under long-term administration of a neuroleptic.

It has been hypothesized that free radicals play a causative role in tardive dyskinesia, which is an inveterate movement disorder caused by chronic administration of neuroleptics. To verify this hypothesis, rats were reared while being regularly treated with water containing a neuroleptic, haloperidol (HPD), for 1 year (HPD group). The changes in the striatal hydrogen peroxide content of the rats in the HPD and control groups were measured by using a Pt-disk microelectrode while the animals were in a freely moving state following intraperitoneal administration of HPD (HPD challenge). We also performed electron spin resonance (ESR) detection of lipid radicals in the striatum before the HPD challenge. HPD challenge led to significant elevation of the intrastriatal hydrogen peroxide in all animals, but the elevation in the HPD group was smaller than that in the control group. However, in the HPD group, marked ESR signals of intrastriatal lipid radicals were observed. We think that these results support the hypothesis on the role of free radicals in tardive dyskinesia.

Animals↗

Monitoring of regional cerebral oxygenation by near-infrared spectroscopy during continuous retrograde cerebral perfusion for aortic arch surgery.

OBJECTIVE: To assess the value of monitoring of regional cerebral oxygen saturation (rSO2) during aortic arch surgery using continuous retrograde cerebral perfusion (CRCP) in conjunction with profound hypothermic circulatory arrest (HCA). METHODS: The rSO2 of 12 consecutive patients was monitored non-invasively using near-infrared spectroscopy (NIRS) and the data were analyzed statistically. RESULTS: The mean duration of HCA with CRCP was 62-/+14.1 min. The mean CRCP flow rate was 226+/-163 ml/min. Surgical outcomes were favorable with only a single hospital death (8.3%). However, the rSO2 decreased gradually in all patients during HCA, even combined with CRCP, and fell to 46+/-8.7% on average. It did not change so greatly before HCA and returned finally to its initial level at the end of re-warming. Only one patient developed a permanent neurologic deficit; this patient showed the greatest decrease of rSO2 from 56% to 29% after the longest HCA of 88 min. Two parameters, End-rSO2 (the ratio of post- to pre-HCA rSO2) and delta-rSO2 (the rate of decrease from preto post-HCA rSO2) were obtained since the initial values of rSO2 before surgery differed. There were linear correlations between the CRCP flow rate and each of these two parameters. A multiple regression analysis also revealed a linear equation relating the parameters, which allowed prediction of the safe duration of HCA in different conditions of CRCP and a more favorable adjustment of the CRCP condition in each patient. CONCLUSIONS: The study suggests that the combination of HCA and CRCP has a limit of safe duration in spite of its potential usefulness for brain protection, and that rSO2 monitored by NIRS is useful in testing for adequate brain protection. It is hoped that monitoring of rSO2 can facilitate prediction of the safe duration of HCA with CRCP and a more favorable adjustment of CRCP.

Aortic Aneurysm, Thoracic↗