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Biomedical subjects

Y Ueda

Publications and source records attributed to Y Ueda.

At least 109 records · Page 6Linked to original sources

The effects of exogenous epinephrine on a convulsive dose of lidocaine: relationship with cerebral circulation.

In order to understand why exogenous epinephrine decreases the convulsive dose of lidocaine, the authors investigated cerebral circulation and plasma lidocaine concentrations in Wistar rats under general anesthesia. In the first experiment, baseline evaluations of each rat's electroencephalogram (EEG), mean arterial pressure (MAP), regional cerebral blood flow (r-CBF), cerebrospinal fluid (CSF) pressure, and cerebral perfusion pressure (CPP) were made. The rats were then assigned to one of three groups: Group L (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 kg/kg/min); and Group E (n=5) received intravenous epinephrine (2.5 microg/kg/min). Cumulative doses of lidocaine at the onset of EEG spike activity in Groups L and LE were compared. Blood-brain barrier (BBB) permeability was evaluated by observing extravasation of Evans blue (EB) dye. In the second experiment, additional rats were allocated to two treatment groups: Group L' (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE' (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 microg/kg/min). Brain tissue oxygen partial pressure (PtO2) was monitored during infusion, and arterial and sagittal sinus blood samples were obtained immediately after the onset of EEG spike activity to determine plasma lidocaine concentration. The convulsive dose of lidocaine was significantly decreased when lidocaine was administered with epinephrine (Group L: 61.5+/-5.3 mg/kg (mean+/-SD); Group LE: 30.1+/-4.0 mg/kg) (p < 0.05), but there were no significant differences in plasma lidocaine concentration among these groups. R-CBF, CSF pressure, and CPP immediately before EEG spike activity were higher in Group LE than in Group L. Neither decreased PtO2 nor extravasation of EB was observed in rats treated with epinephrine and lidocaine, excluding cerebral ischemia and BBB breakdown from possible mechanisms by which epinephrine decreased the convulsive dose of lidocaine. None of the rats in Group E exhibited EEG findings suggestive of a preconvulsive state, ruling out a convulsive effect of epinephrine itself. The results suggest that an increase in lidocaine supply to the brain caused by increased CBF causes the low cumulative dose of lidocaine at the onset of convulsion in rats given lidocaine plus epinephrine.

Adrenergic Agonists

Expression of target genes by coinfection with replication-deficient viral vectors.

An in vivo transcription system was developed by coinfection of cells with replication-deficient viral vectors. Recombinant baculovirus (AcT7HCVLuc) and fowlpox virus (FPVT7HCVLuc) carrying a cDNA of the hepatitis C virus (HCV) minigene encoding the HCV 5' untranslated region (UTR), a luciferase gene and the 3' UTR, including the 98 nt extra sequence, under the control of the T7 promoter were constructed. The HCV minigene was synthesized in various cells by coinfection with one of these two viruses and recombinant baculovirus (AcCAT7) or adenovirus (AdexCAT7) expressing T7 RNA polymerase under the control of a mammalian promoter. Only a low level of luciferase expression was obtained in cells coinfected with AcT7HCVLuc and either AcCAT7 or AdexCAT7. In contrast, high-level luciferase expression was detected when the same cells were coinfected with FPVT7HCVLuc and either AcCAT7 or AdexCAT7. We further constructed a recombinant fowlpox virus with its HCV minigene extended to contain the whole HCV core protein region. Significantly high levels of expression of HCV core protein were detected in MT-2, COS7 and Vero cells by coinfection with the recombinant fowlpox virus and AdexCAT7. A coinfection system consisting of recombinant fowlpox virus and AdexCAT7 was established for high level of expression of a target gene in various cells.

Adenoviridae

Life-threatening hemorrhage in a patient with gastric cancer and acquired hemophilia.

We report a case of a patient with life-threatening hemorrhage caused by the presence of acquired factor VIII inhibitors after gastrectomy for signet-ring cell carcinoma of the stomach. Acquired factor VIII inhibitors should be taken into consideration as a cause of acquired bleeding tendency among patients with gastrointestinal malignancies especially when the coagulation tests are unusual.

Aged

Changes in platelet demand in association with the spread of autologous peripheral blood progenitor cell transplantation.

Changes in platelet demand accompanying widespread application of autologous peripheral blood progenitor cell transplantation (APBPCT) were anticipated. The differences in the transfused volume of platelet concentrate (PC) among 8 patients with malignant lymphoma who were treated with APBPCT and 10 patients with malignant lymphoma who were not treated with APBPCT, although peripheral blood progenitor cell harvests had been performed, were studied. The former was 81 Japanese PC units more than the latter. Considering the supplied volume of PC from Red Cross blood centers and the number of APBPCTs in 1996 in Japan, the Japanese demand for PC increases by 0.16% for enforced APBPCT versus 0.36%, which includes the PC demand necessary in all treatment courses. The total increment in PC demand associated with APBPCT is not large enough to threaten the PC supply of Japan even if the number of APBPCTs increases rapidly.

Adult

Augmentation of axial dispersion by intermittent oscillatory flow.

The efficiency of axial gas dispersion during ventilation with high-frequency oscillation (HFO) is improved by manipulating the oscillatory flow waveform such that intermittent oscillatory flow occurs. We therefore measured the velocity profiles and effective axial gas diffusivity during intermittent oscillatory flow in a straight tube to verify the intermittency augmentation effect on axial gas transfer. The effective diffusivity was dependent on the flow patterns and significantly increased with an increase in the duration of the stationary phase. It was also found that the ratio of effective diffusivity to molecular diffusivity is two times greater than that in sinusoidal oscillatory flow. Moreover, turbulence during deceleration or at the beginning of the stationary phase further augments axial dispersion, with the effective diffusivity being over three times as large, thereby proving that the use of intermittent oscillatory flow effectively augments axial dispersion for ventilation with HFO.

Diffusion

[Shigella dysenteriae strains possessing a new serovar (204/96) isolated from imported diarrheal cases in Japan].

Five Shigella strains isolated from stool cultures of imported diarrheal cases in Japan, did not react to any antisera of the established Shigella serovars. These strains had the typical biochemical characteristics of Shigella dysenteriae, and were biochemically identical. All strains were positive in the Sereny test and other tests for invasivness; these indicate that they can cause shigellosis in humans. The results of antigenic analysis revealed that they did not belong to any of the recognized or provisional serovars, and were serologically indistinguishable. They had the same drug-resistance pattern (CP.TC.SM.ABPC.ST) and plasmid-profile. Strain 96-204 is designated as the test strain for this new serovar.

Anti-Bacterial Agents

Creating a functional opioid alkaloid binding site in the orphanin FQ receptor through site-directed mutagenesis.

Although much has been learned about the mechanisms of ligand selectivity between different opioid receptor subtypes, little is known about the common opioid binding pocket shared by all opioid receptors. The recently discovered orphanin system offers a good opportunity to study the mechanisms involved in the binding of opioid versus nonopioid ligands. In the current study, we adopt a "gain of function" approach aimed at shifting the binding profile of the orphanin FQ receptor toward that of the opioid receptors. After two rounds of mutagenesis, several orphanin FQ receptor mutants can be labeled with the opiate alkaloid [3H]naltrindole and show greatly increased affinities toward the opiate antagonists naltrexone, nor-binaltrophine HCl, and (-)-bremazocine. These orphanin FQ receptor mutants also display stereospecificity similar to that of opioid receptors. Furthermore, the orphanin FQ receptor mutant that has the best affinities toward the opioid alkaloids shows, in the presence of GTP and high salt concentration, an affinity-shift profile similar to that of the delta receptor. Most strikingly, the same mutant exhibits naltrindole-sensitive etorphine-stimulated [35S]guanosine-5'-O-(3-thio)triphosphate binding, whereas the effect of etorphine on GTP binding cannot be inhibited by naltrindole in the wild-type receptor. Our results indicate that 1) several residues in the orphanin FQ receptor are critical to its selectivity against the opiate alkaloids, particularly antagonists; and 2) mutating these residues to those of the opioid receptor at the corresponding position preserves the agonist/antagonist nature of opiate alkaloids as they interact with the mutant receptor. It is reasonable to hypothesize that the corresponding residues in the opioid receptors may form a functional common binding pocket for opiate alkaloids. These findings may be helpful to medicinal chemists in designing ligands for the orphanin FQ receptor based on the structure of the opiate alkaloids.

Amino Acid Substitution

Effects of ischemic preconditioning on contractile and metabolic function during hypoperfusion in dogs.

We examined the effects of ischemic preconditioning (i.p.) on metabolic and contractile function during coronary hypoperfusion in dogs. After the left anterior descending coronary artery (LAD) was occluded for 5 min (i.p.) and reperfused for 10 min, coronary blood flow (CBF) of the LAD was decreased to 33% of the control. I.p. increased (P < 0.05) lactate extraction ratio and the pH of coronary venous blood and decreased (P < 0.05) myocardial oxygen consumption and fractional shortening during hypoperfusion compared with those in the control group, although i.p. did not change the endocardial-to-epicardial blood flow ratio of the regional myocardium during hypoperfusion. I.p. increased (P < 0.05) the adenosine levels in coronary venous blood during hypoperfusion. I.p. increased (P < 0.05) myocardial ecto-5'-nucleotidase activity. Administration of 8-sulfophenyltheophylline or alpha, beta-methyleneadenosine 5'-diphosphate blunted the i.p.-induced changes in metabolic and contractile parameters during hypoperfusion. These results suggest that i.p. reduced the severity of anaerobic myocardial metabolism of ischemic hearts by increasing the adenosine levels via an extracellular pathway.

5'-Nucleotidase

Possible role of nitric oxide in IgE-mediated allergic cutaneous reaction in mice.

The role of nitric oxide (NO) in the development of allergic cutaneous reactions in mice was investigated. A biphasic cutaneous reaction composed of an immediate-phase edema and a late-phase edema was evoked by epicutaneous application of 2,4-dinitrofluorobenzene on the ear of mice passively sensitized with mouse anti-dinitrophenol monoclonal IgE. Two NO synthase inhibitors, L-NG-nitroarginine methyl ester (L-NAME) and NG-monomethyl-L-arginine, significantly inhibited both phases of the IgE-mediated biphasic cutaneous reaction. Simultaneous treatment with L-arginine attenuated the inhibitory effect of L-NAME. An NO donor, 3-morpholinosydononimine-N-ethylcarbamide, caused a potent edematous reaction in the mouse ear. Furthermore, L-NAME inhibited the cutaneous reactions caused by both interleukin-1beta and tumor necrosis factor-alpha, putative mediators of the late-phase edema in the biphasic cutaneous reaction. These results indicate that a gaseous mediator, NO, participates, at least in part, in the development of ear edema in the IgE-mediated biphasic cutaneous reaction in mice.

Animals

Classification of Lactobacillus helveticus strains by immunological differences in extracellular proteinases.

Polyclonal antibodies against an extracellular proteinase of Lactobacillus helveticus CP53 were raised. The antibodies reacted with a 170-kDa enzyme with activity and a 53-kDa protein that seemed to be a degradation product of the 170-kDa proteinase from results of immunoblotting. The antibodies reacted also with a 45-kDa extracellular proteinase of L. helveticus CP790. However, monoclonal antibodies to the CP790 proteinase did not react with the proteinase of L. helveticus CP53. Seventeen strains of L. helveticus were tested for immunological reactivity with the two kinds of antibodies. The strains all had the same reactivity as either strain CP53 or strain CP790. Eleven strains with the 45-kDa proteinase were identified as L. helveticus biovar jugurti because they did not ferment maltose, four other strains with the 170- and 53-kDa proteins were identified as L. helveticus biovar helveticus because they fermented maltose. The remaining two strains dit not fit this pattern; they had both the 170- and 53-kDa proteins, but classification by their sugar utilization showed them to be L. helveticus biovar jugurti.

Animals

Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product: carbonyl stress in uremia.

Advanced glycation end product (AGE) formation is related to hyperglycemia in diabetes but not in uremia, because plasma AGE levels do not differ between diabetic and nondiabetic hemodialysis patients. The mechanism of this phenomenon remains elusive. Previously, it was suggested that elevation of AGE levels in uremia might result from the accumulation of unknown AGE precursors. The present study evaluates the in vitro generation of pentosidine, a well identified AGE structure. Plasma samples from healthy subjects and nondiabetic hemodialysis patients were incubated under air for several weeks. Pentosidine levels were determined at intervals by HPLC assay. Pentosidine rose to a much larger extent in uremic than in control plasma. Pentosidine yield, i.e., the change in pentosidine level between 0 and 4 wk divided by 28 d, averaged 0.172 nmol/ml per d in uremic versus 0.072 nmol/ml per d in control plasma (P < 0.01). The difference in pentosidine yield between uremic and control plasma was maintained in samples ultrafiltrated through a filter with a 5000-Da cutoff value and fortified with human serum albumin (0.099 versus 0.064 nmol/ml per d; P < 0.05). Pentosidine yield was higher in pre- than in postdialysis plasma samples (0.223 versus 0.153 nmol/ml per d; P < 0.05). These results suggest that a large fraction of the pentosidine precursors accumulated in uremic plasma have a lower than 5000 Da molecular weight. Addition of aminoguanidine and OPB-9195, which inhibit the Maillard reaction, lowered pentosidine yield in both uremic and control plasma. When ultrafiltrated plasma was exposed to 2,4-dinitrophenylhydrazine, the yield of hydrazones, formed by interaction with carbonyl groups, was markedly higher in uremic than in control plasma. These observations strongly suggest that the pentosidine precursors accumulated in uremic plasma are carbonyl compounds. These precursors are unrelated to glucose or ascorbic acid, whose concentration is either normal or lowered in uremic plasma. They are also unrelated to 3-deoxyglucosone, a glucose-derived dicarbonyl compound whose level is raised in uremic plasma: Its addition to normal plasma fails to increase pentosidine yield. This study reports an elevated level of reactive carbonyl compounds ("carbonyl stress") in uremic plasma. Most have a lower than 5000 Da molecular weight and are thus partly removed by hemodialysis. Their effect on pentosidine generation can be inhibited by aminoguanidine or OPB-9195. Carbonyl stress might contribute to AGE modification of proteins and thus to clinically relevant complications of uremia.

Aged

Plasma levels of pentosidine in diabetic patients: an advanced glycation end product.

Nonenzymatic reactions between glucose and proteins yield advanced glycation end products (AGE) such as pentosidine. AGE accumulate in diabetic patients, alter the structure and function of tissue proteins, stimulate cellular response, and have thus been implicated in diabetic tissue damage. The present study was undertaken to assess the factors determining plasma total pentosidine level in diabetic patients and the possible relation between plasma pentosidine level and diabetic complications. In diabetic patients, including patients with renal failure, plasma pentosidine levels, assessed by HPLC assay, were correlated with serum creatinine (P < 0.0001). In patients with normal renal function, pentosidine levels were correlated with blood glucose control (hemoglobin Alc: P = 0.0028; fructoselysine: P = 0.0133), serum creatinine (P = 0.029), patient age (P = 0.0416), duration of diabetes (P = 0.0431), and total cholesterol (P = 0.0056) and LDL-cholesterol (P = 0.0208). Multiple regression analysis revealed an independent influence of hemoglobin Alc and serum creatinine on pentosidine levels (r2 = 0.216, P = 0.0026). Pentosidine levels were higher in patients with than in those without hypertension (P = 0.043) or ischemic heart diseases (P = 0.0061). No such differences were observed between patients with and without albuminuria or retinopathy. Multiple regression analysis revealed an independent influence of plasma pentosidine on the presence of hypertension (r2 = 0.129, P = 0.0382) and of plasma pentosidine and HDL-cholesterol on the presence of ischemic heart disease (r2 = 0.326, P = 0.0012). The present study demonstrated that plasma pentosidine level was significantly influenced by the quality of glycemic control and renal function. Pentosidine level was also correlated with hypertension and ischemic heart disease, and might be taken as a biomarker of diabetic cardiovascular risk.

Adult

[Prevalence of dementia and its subtypes in a rural area in Japan].

The prevalence of dementia in Japan in 1985 for people aged 65 years or older was 4.8%. Vascular dementia (VD) has been reported to be the commonest subtype A report from Tokyo in 1970 showed that it was 2.8 times more frequent than Alzheimer type dementia (SDAT). We assessed the prevalence of dementia in a rural area (population: 12,931, 25.3% were 65 years or older in 1994) in Kyoko. First, we questioned subjects about their demographic circumstances, memory disturbance, apraxia (agnosia) and daily activities. Our questionnaire was answered by 3.132 (95.8%) subjects, and 2,280 of them agreed to be examined by neurologists. Those who met the appropriate criteria of the DSM-III-R and NINCDS-ADRDA were diagnosed with dementia. By use of the Hachinski ischemic score (HIS), we distinguished VD from non-vascular dementia. In this study patients with non-vascular dementia were diagnosed with SDAT by the neurologists. Analysis of the data revealed that 4.8% of the study population was demented. According to the HIS results, only 3 of 15 had vascular dementia. The prevalence of dementia was the same as the average prevalence in Japan even though the elderly population of this town was twice as high as the average. It is hard to determine the prevalence of dementia in any community. Many factors must be taken into consideration: the coverage rate, the criteria for dementia, and whether to include institutionalized residents. The prevalence of dementia will increase with the aging of the population, and we must collect accurate data in order to plan efficiently.

Aged

[Spinal subarachnoid hemorrhage presenting as disturbance of consciousness with severe hypoglycorrhachia].

We report the case of an 84-year-old woman with spinal subarachnoid hemorrhage who presented with disturbance of consciousness and nuchal stiffness, bloody cerebrospinal fluid and severe hypoglycorrhachia. Initially, it was difficult to determine whether this was a case of spinal subarachnoid hemorrhage, purulent meningitis, or hemorrhagic encephalitis, because of the nuchal stiffness, disturbance of consciousness and severe hypoglycorrhachia. It is known that intracranial subarachnoid hemorrhage is accompanied by mild hypoglycorrhachia, but descriptions of glucose levels in cerebrospinal fluid in cases of spinal subarachnoid hemorrhage are rare. This case suggests that both spinal subarachnoid hemorrhage and intracranial subarachnoid hemorrhage are associated with hypoglycorrhachia. Furthermore, spinal subarachnoid hemorrhage is frequently accompanied by disturbance of consciousness. Therefore, sudden back pain or lumbago might not be interpreted as indicators of spinal subarachnoid hemorrhage, because patients, particularly elderly patients, may lose consciousness. We emphasize that the possibility of spinal subarachnoid hemorrhage should be considered in patients with disturbance of consciousness or hypoglycorrhachia even if they do not complain of sudden back pain.

Aged

Comparison of fluorine-18-FDG PET and thallium-201 SPECT in evaluation of lung cancer.

UNLABELLED: We compared the diagnostic value of [18F]2-fluoro-2-deoxy-D-glucose (FDG) PET imaging and 201Tl SPECT imaging in the detection of primary lung cancer and mediastinal lymph node metastases. METHODS: Thirty-three patients with histologically-proven primary lung cancer were examined with both FDG PET and TI SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the tumor-to-nontumor activity ratio (T-to-N ratio) was calculated. RESULTS: Although both techniques delineated focal lesions with an increase in tracer accumulation in 28 patients, PET identified three additional patients in whom Tl SPECT images did not visualize any lesions on both early and delayed scans. In the detection of lung cancer of less than 2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than did Tl SPECT early scan (one of seven, 14.3%) and delayed scan (four of seven, 57.1%). Neither technique visualized any lesions in two patients who had bronchioloalveolar carcinoma. The T-to-N ratio was significantly higher with FDG PET (10.39 +/- 6.63) than it was with Tl SPECT (early scan, 2.37 +/- 0.86; delayed scan, 3.01 +/- 1.01) (p < 0.0001), whereas there was significant positive correlation between the FDG T-to-N ratio and the thallium T-to-N ratio (p < 0.01). Twenty-two patients had thoracotomies. Regarding the staging of mediastinal nodes, FDG PET detected mediastinal lymph node metastasis that was negative on Tl SPECT, whereas both techniques excluded tumor involvement in enlarged node at CT. CONCLUSION: Both techniques have clinical value for the noninvasive detection of primary lung cancer that is 2 cm or greater in diameter. However, if a PET camera is available, FDG PET is considered the method of choice for the evaluation of patients with suspected primary lung cancer that is less than 2 cm in diameter.

Adenocarcinoma

A case of bowel necrosis due to acute mesenteric ischemia following pulsatile cardiopulmonary bypass.

We report a case of fatal bowel necrosis possibly caused by pulsatile cardiopulmonary bypass (CPB). An 80-year-old female underwent emergency coronary artery bypass grafting (CABG) for unstable angina. Pulsatile CPB was applied because of stenosis of bilateral carotid and renal arteries. On the third postoperative day, total bowel necrosis due to acute mesenteric ischemia was revealed at emergency laparotomy before her death. Pulsatile CPB may increase the risk of distal embolism of dislodged plaque in cases with severe aortic atheromatosis.

Acute Disease