Are autoimmune mechanisms involved in critical illness polyneuropathy?
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to N Seo.
Explore the source record for details and available documents.
We previously found that acute administration of a nitric oxide synthase (NOS) inhibitor (N omega-nitro-L-arginine methyl ester [L-NAME]) does not reduce the minimum alveolar anesthetic concentration (MAC) of halothane in rats. However, a recent study has suggested that brain NOS activity could not be inhibited by more than approximately 50% by acute administration of L-NAME. To investigate the effect of marked inhibition of NOS activity on the MAC of halothane, we measured cerebellar NOS activity, cerebellar cyclic guanosine monophosphate (cGMP) levels, and halothane MAC in rats chronically treated with L-NAME and compared the results to those of the saline-treated control group. Although the cerebellar NOS activity and cGMP levels were significantly decreased (14% and 2.7% of control, respectively) by L-NAME, the value of the halothane MAC was not significantly affected. These results suggest that the anesthetic action of halothane, as measured by its MAC in rats, is not related to NOS activity or cGMP levels in the brain.
Explore the source record for details and available documents.
We report the usefulness of monitoring hepatic venous saturation (ShVO2) during open heart surgery for a patient with severe liver dysfunction. The patient was a 55-year-old man who had been suffering from acute aortic regurgitation due to bacterial endocarditis. Indocyanine green retention test at 15 min was 55%. Serum GOT, GPT and T bilirubin were 56 U.l-1, 35 U.l-1 and 1.5 mg.dl-1 respectively. Aortic valve replacement was scheduled in spite of severe liver dysfunction because amelioration of congestive heart failure after the operation was expected to improve liver dysfunction to the previous chronic state. Anesthesia was induced and maintained by intermittent administration of diazepam and low dose of fentanyl with 100% oxygen. After induction, we inserted a balloon tipped pulmonary catheter with ultra-red beam into hepatic vein by fluoroscopy guidance and monitored ShVO2 as an index of hepatic oxygen supply/demand balance. During re-insertion of a thoracic catheter, we could detect the continued decrease in hepatic vein saturation even after the improvement of systemic circulatory state. Postoperatively, liver function became slightly worse for a short period and improved thereafter. These results suggest that ShVO2 monitoring is clinically useful in detecting hepatic oxygen supply/demand imbalance which circulatory monitoring could not uncover during open heart surgery.
In an attempt to obtain monoclonal antibodies specific to tumor-associated antigens, C3H/He mice were immunized with syngeneic MM2 tumor cells, and the primed spleen cells were fused with P3-X63-Ag8.653 myeloma cells. The outgrowth of hybridomas, however, was extremely low and monoclonal antibodies were not obtained. The reason for the low hybridoma growth was studied. It was found that MM2 cells used as the immunogen, the fusion partner myeloma cells and the resulting hybridomas shared at least one tumor-associated antigen, namely Q5 antigen. Because of this common antigen, cytotoxic cells, presumably cytotoxic T lymphocytes, which were lytic to the hybridomas, were induced during the culture for generation of the hybridomas. Removal of lysosome-rich cells, including cytotoxic T lymphocytes, from the primed spleen cells before the fusion by treatment with leucine methyl ester, a lysosomotropic agent, drastically improved the outgrowth of hybridomas. By this method, seven stable hybridoma clones producing monoclonal antibodies specific to tumor-associated antigens were obtained. Two of the seven clones were found to secrete monoclonal IgM species, which reacted with the extra-cellular region of the Q5 antigen. This procedure will be an option when production of monoclonal antibodies specific to cell-surface antigens is intended and outgrowth of hybridomas is unexpectedly low.
In a previous study, we demonstrated that halothane and isoflurane inhibit binding of thromboxane A2 to its receptors on human platelets and thus inhibit prostanoid-induced aggregation strongly. The aim of this study was to determine whether volatile anaesthetics inhibit prostanoid-induced vasoconstriction preferentially. Rat isolated aortic rings were mounted in organ baths and their isometric tension was measured. They were contracted with STA2 (a stable thromboxane A2 analogue), prostaglandin F2 alpha (PGF2 alpha), phenylephrine, and 20 mM KCl, and then exposed to halothane (0.5-3%), isoflurane (0.5-3%), and sodium nitroprusside (SNP, 10(-9)-3 x 10(-7) M). Halothane (2-3%) and isoflurane (2-3%) induced greater relaxation of aortic rings precontracted with STA2 and PGF2 alpha than of those precontracted with phenylephrine (P < 0.01). Halothane induced greater relaxation of rings precontracted with KCl than phenylephrine only at 3%, whereas isoflurance relaxed rings precontracted with KCl more than those with phenylephrine at 0.5, 2 and 3% (P < 0.05). In contrast, SNP relaxed rings precontracted with PGF2 alpha. KCl and phenylephrine equally, but induced smaller relaxations of those precontracted with STA2 (P < 0.05). We conclude that halothane and isoflurane inhibit prostanoid-induced vasoconstriction preferentially, possibly by interacting with prostanoid receptors.
In 20 patients undergoing topical anesthesia for gastroscopic examination, serum concentrations of lidocaine and its metabolite, monomethylglycinexylidide (MEGX), were measured. Patients were divided randomly into two groups: a gel group, in which 5 ml of 2% lidocaine gel was applied to the throat for 20 minutes; and a solution group, in which 40 ml of 2% lidocaine solution was administered by gargling for five minutes. The effect of oropharyngeal anesthesia was comparable in both groups. In the gel group, the serum levels of lidocaine and MEGX were not elevated at 15 minutes after application of the anesthetic. However, in the solution group, a rise in both serum lidocaine and MEGX at 15 minutes after anesthesia was detected in some of the patients (40%). Increased serum MEGX concentrations, which correlated well with serum lidocaine concentrations, were associated with the age of the patient (r = 0.606; p < 0.05), but not with height or weight. As a topical anesthetic for endoscopic examination, we prefer lidocaine gel to lidocaine solution, because the latter might be absorbed more rapidly and unpredictably in some, especially aged patients.
To provide a neurochemical basis for the central nervous system actions of nitrous oxide, the changes of brain dopamine (DA), serotonin (5-HT), norepinephrine (NE), and metabolites of DA and 5-HT were studied in rats. Thirty male Wistar rats were assigned to one of five groups according to the type of gas and the duration of gas exposure. The rats in one group, which served as control, were exposed to air for 30 min, and the rats in four other groups were exposed to 75% nitrous oxide in oxygen for 0.5, 1, 2, and 4 h, respectively. Animals were killed with microwave irradiation, and the brains were divided into seven sections: the cerebral cortex, cerebellum, striatum, hippocampus, midbrain-thalamus, hypothalamus, and medulla-pons. The contents of NE, DA, 3,4-dihydroxyphenyl-alanine (DOPAC), homovanillic acid (HVA), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) in each discrete area were measured with high-performance liquid chromatography. Nitrous oxide had no significant effect on the contents of NE, 5-HT, nor 5-HIAA, but decreased that of DA in the striatum and midbrain-thalamus after 4 h of exposure (P < 0.05). Levels of DOPAC, but not DA, in the cerebral cortex and medulla-pons were increased significantly at exposures up to 2 h (P < 0.05), but were not significant from control levels after a 4-h exposure. Increased levels of DOPAC indicate that nitrous oxide increases dopaminergic neuronal activities in the mesocortical projection and the medullary network.(ABSTRACT TRUNCATED AT 250 WORDS)
We analyzed the effect of a new volatile anesthetic, sevoflurane (2%-5% in oxygen) on the electroencephalogram (EEG) of the neocortex, amygdala, and hippocampus, cortical somatosensory evoked potential (SEP), and brainstem reticular multiunit activity (R-MUA) in cats. Sevoflurane suppressed the background activity of the neocortex more than the amygdala and hippocampus. With increasing concentration of sevoflurane, the cortical EEG progressed from high-amplitude slow waves to a suppression-burst pattern, which was followed by an isoelectric pattern and then spikes with isoelectricity. The amplitude of the SEP was augmented and the R-MUA was suppressed by sevoflurane in a dose-related manner. Repetitive peripheral electrical stimulation induced generalized seizures at 5% sevoflurane in 2 of 13 cats. These results suggest that sevoflurane suppresses the background central nervous system electrical activities in a dose-related manner, leaving the reactive capabilities facilitated at deep anesthesia.
To evaluate the effectiveness of low dose dibutylic cyclic AMP (DBcAMP) during coronary artery bypass graft surgery, we compared circulatory and endocrine-metabolic parameters among the three different doses: (1) DBcAMP 10 microg.kg-1.min-1 (A-10 group), (2) DBcAMP 20 microg.kg-1.min-1 (A-20 group), and (3) control (A-0 group). In the A-10 group, perfusion pressure was significantly higher than in the A-0 group at the point of maximum cooling and at the start of warming during cardiopulmonary bypass (CPB), while peripheral vascular resistance was significantly lower than in the A-0 group at the closing of CPB. On the contrary, in the A-20 group, perfusion pressure was significantly lower than in the A-0 group at the point of maximum cooling and the start of warming during CPB, while peripheral vascular resistance was significantly lower than in the A-0 group at the start of warming and the closing of CPB. Among these groups, the hourly urine volume during CPB was significantly largest in A-10 group. Endocrine-metabolic parameters showed no statistic difference among these groups. These results suggest that the administration of DBcAMP 10 microg.kg-1.min-1 during CPB might improve the cardiac performance and maintain the tissue perfusion without the endocrine-metabolic deterioration.
In order to determine whether lidocaine metabolism, as the formation of monoethylglycinexylidide (MEGX), could be used as a quantitative index of perioperative liver function, serum levels of MEGX in 31 surgical patients were measured and compared with the results of conventional liver function tests. A significant correlation was found between the values of MEGX and ICGR15 in 20 of the 31 patients. The values of ICGR15 were lower than 20% in patients whose MEGX values were above 60 ng/ml and 20% or higher in those with MEGX values of lower than 60 ng/ml. There was also a significant correlation between MEGX values and antithrombin III values, and between MEGX values and the postoperative maximum levels of aspartate aminotransferase. However, no correlation was found between MEGX values and other preoperative conventional liver function tests in any of the 31 patients. We suggest that a cut-off MEGX value of 60 ng/ml be used as an indicator for satisfactory preoperative liver function. MEGX formation could be a useful prognostic index for patients who have undergone surgical procedures for liver disease, and employed as a quantitative assessment of perioperative liver function.
Tumor-specific expression of Qa-2k antigen coded by the Q5k gene on various mouse tumor cells and immunological response of the host mice to the antigen have been demonstrated [Seo et al. (1992) J Exp Med 175: 547; Tanino et al. (1992) Cancer Immunol Immunother 35: 230]. The possibility was examined that Qa-2 antigen is one of the recognition target molecules of immunopotentiator-induced, H-2-nonrestricted tumoricidal lymphocytes of Qa-2-mice. Lymphocytes stimulated in vivo with P. acnes or culture-induced anomalous killers of B6.K1 mice did not exhibit significant in vitro cytotoxicity against B6.K1 lymphoblasts but lysed their Qa-2,3-congenic counterpart B6 lymphoblasts. To demonstrate the Qa-2 specificity of such cytotoxic cells more precisely, an L cell transformant clone (LQ7b/Kb), which expressed the alpha 1 and alpha 2 domains of the Qa-2 antigen (Q7b gene product), was generated by transfecting a cloned plasmid DNA containing a hybrid gene constructed from the 5' half of the Q7b gene and the 3' half of the H-2Kb gene (pQ7b/Kb). Using LQ7b/Kb cells as the target cells and the nylon-wool-nonadherent fraction of lymphocytes from P. acnes-stimulated (C3H/He x B6.K1)F1 mice (H-2k, Qa-2-) as the effector cells of the in vitro cytotoxicity reaction, the presence of cytotoxic cells that recognize the alpha 1/alpha 2 region of the Q7b gene product was demonstrated. The cytotoxic activity was dependent on T cells bearing T cell receptors of the gamma/delta type (TCR gamma/delta). The (C3H/He x B6.K1)F1 effector cells, as well as the B6.K1 effector cells also lysed BW5147 lymphoma cells (Qa-2k+) derived from AKR mice (Qa-2-, H-2k). By target-competition experiments it was shown that some of the effector cells lytic to BW5147 were identical to those that lysed LQ7b/Kb. Therefore some of the tumoricidal cells induced by the immunopotentiator interact with the target tumor cells through recognition of the alpha 1/alpha 2 region of the Qa-2k tumor antigen by TCR gamma/delta.
Thirty-eight human cancer cell lines and subclones derived from 12 different organs were screened for vitronectin secretion in their culture media. By immunoblotting analysis we detected high secretion by three out of five hepatoma cell lines tested but no secretion by the others. In addition, significant secretion was observed in seven non-hepatic cancer cell lines and subclones derived from the cervix, lung, and pancreas. These vitronectin-secreting cells included PLC/PRF/5, HuH-6 #5, HuH-7, HeLa S3, HeLa.P3 #2, #3, #6, #8, A549, and MIAPaCa-2. The results were further confirmed by quantitative analysis using sandwich enzyme-linked immunoassay, and activity analysis of cell attachment promotion on Western blotted filters.
Immunological and biochemical characteristics of the Qa-2 murine nonclassical histocompatibility class 1 antigen expressed on tumor cells derived from H-2k (Qa-2-) mice were studied. It was found that the Qa-2 antigen on normal H-2b lymphocytes reacted with Qa-2-specific monoclonal antibodies (mAbs) 34-1.2, 59 (both specific to the alpha 1/alpha 2 region) and 141-15.8 (specific to the alpha 3 domain), and the Qa-2 antigen on H-2k tumor cells (Qa-2k antigen) reacted with mAbs 59 and 141-15.8, but not with 34-1.2. The normal Qa-2 antigen was susceptible to treatment with phosphatidylinositol-specific phospholipase C, but the Qa-2k antigen was insensitive to it. By Northern hybridization, polymerase chain reaction (PCR) studies on cDNA, Southern hybridization, Western blotting, and nucleotide sequence analysis, the Q5k gene was identified as the gene encoding the Qa-2k antigen expressed on BW5147 lymphoma cells derived from a mouse of AKR strain (H-2k, Qa-2-). The nucleotide sequence of PCR-amplified BW5147 Q5k cDNA showed complete agreement with the reported sequence of exons 1-5 of the Q5k gene of C3H/He. It also showed complete deletion of the region corresponding to exons 6 and 7, and a very short coding region in exon 8, resulting in very short cytoplasmic domain of the product compared with regular class 1 antigens. These characteristics were expected from the reported Q5k genomic sequence. These results revealed that the Qa-2k antigen was distinct from the normal Qa-2 antigen expressed on H-2b lymphocytes although it cross-reacted with some Qa-2-specific mAbs.
Serum from C3H/He mice, which show regression of MM2 tumor cells after transplantation and removal (regressor serum, RS) contains non-gammaglobulin components that cross-react with various tumor cells of mice [22, 23]. In addition to tumor cells, various allogeneic lymphocytes are also susceptible to an RS-dependent lymphocyte-mediated cytotoxic reaction. To identify tumor cell surface antigens that cause the cross-reactive host response, the serum components were analyzed by absorption of RS with allogeneic lymphocytes. RS components were found to recognize allogeneic lymphocyte antigens including Qa-2 and Ly6.2. Specificity for the Qa-2 antigen was further tested using Qa-2-congenic mice. The expression of Qa-2 antigen was detected on the surfaces of MM2 and other tumor cells derived from H-2k mice (seven among nine cell lines tested) by a membrane immunofluorescence method using a Qa-2-specific mAb. Physical characteristics of the Qa-2-specific component in RS were determined and found to differ from those of regular IgGs but to be similar to those of IgDs. Using an enzyme-linked immunosorbent assay with an IgD-specific mAb and Qa-2-lacZ fusion protein, the existence of IgD in RS with specificity for Qa-2 was confirmed. These results suggest that the RS component with Qa-2 specificity is an IgD, the specificity and physiological role of which are unknown.
Explore the source record for details and available documents.
A 23-year-old male with complete collapse of the right lung due to spontaneous pneumothorax was admitted 11 days after its onset. Paying close attention to the re-expansion pulmonary edema (REPE), water seal drainage was performed. Following couple episodes of persistent severe cough, four hours later, he developed dyspnea and began to expectorate frothy massive sputum. Chest X-ray revealed pulmonary edema of the entire right lung field. Measurement of total proteins and neutrophil elastase in airway exudates showed 5.5 g/dl (ratio to plasma, 0.89) and 7000 micrograms/l, respectively. Because of marked difference of compliance between bilateral lungs, management with right and left-separated mechanical ventilation and PEEP applied only to the right lung was performed. Although transient mediastinal deviation to the left was observed, successful management was achieved by the maneuver. High concentrations of total proteins and neutrophil elastase in edema fluid suggest that increased vascular permeability due to endothelial cell injury via activated neutrophils is mainly responsible for REPE. In the present case, rapid expansion of the collapsed lung accelerated by severe cough seems to be a predisposing factor of REPE. In patient with prolonged pneumothorax, suppression of cough is thought to be important for the prevention of REPE even with water seal drainage.
Two new natural pteridines have been isolated from the cultured medium of Rhodopseudomonas sphaeroides GM-1. The compounds are tentatively identified as 2-amino-4-hydroxy-6-hydroxy-6-(1,2, 3,4-tetrahydroxybutyl)pteridine and 2-amino-4-hydroxy-6-(3-hydroxy-4-phosphonoxy-1-butenyl)pteridine by degradative experiments and by electrophoretic and paper chromatographic comparison with authentic materials.