[Emergency management of paralysis and hemorrhage].
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Biomedical subjects
Publications and source records attributed to K Takeda.
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In order to compare the extents of metabolic alpha-hydroxylation of the two alkyl groups in unsymmetrical N-nitrosodialkylamines, N-nitroso-N-alkylbutylamines (alkyl = methyl, ethyl, propyl, butyl, and amyl) were incubated with liver microsomes prepared from phenobarbital- or polychlorinated biphenyl (PCB)-treated and untreated rats, and aldehydes produced by the alpha-hydroxylation were determined quantitatively. Although an increased production of aldehydes was observed with the induced microsomes compared with the non-induced microsomes, no marked differences were noted between the two alkyl groups of these unsymmetric nitrosodialkylamines in regard to the extent of alpha-hydroxylation with the exception of N-nitroso-N-methylbutylamine (NMBA). The amount of aldehydes produced from these nitrosamines increased with elongation of the alkyl chain, amounting to 10-30% of the compounds incubated, and the recovery in the incubation (total aldehyde + nitrosamine recovered) was found to be more than 90%, indicating that alpha-hydroxylation is the principal oxidative metabolic pathway of the nitrosamines in vitro. The microsomal alpha-hydroxylation was inhibited by dimethyl sulfoxide and the extent of the hydroxylation was shown to be positively correlated with the mutagenic potency of the nitrosamines. Based on the mutagenic behavior of NMBA tested on Salmonella typhimurium TA1535 and Escherichia coli WP2 hcr- and the extent of the formation of formaldehyde and butyraldehyde from NMBA in the presence of the induced microsomes and S9 mix, it was concluded that NMBA acts as both a methylating and a butylating agent.
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We investigated adrenal medullary function in acute pancreatitis with shock in dog. Pancreatitis was induced by injection of autologous bile into the main pancreatic duct. Adrenal medullary function was examined by basal adrenal catecholamine (CA) output and CA release response to the electrical stimulation of the 1t. splanchnic nerve. Animals were divided into two types--Shock type and non-shock type. In both types, basal CA output increased gradually, but, CA release response in shock type was lower than that in non-shock type. Moreover, both values of basal CA output and CA release response in shock type were lower than those oligemic shock group at the same blood pressure level. On the other hand, no significant difference was observed among these 3 groups on the increase of blood pressure by nerve stimulation, that is, low response of CA release in shock type had no relation with the nerve injury. It was concluded that adrenal medulla was injured in acute pancreatitis with shock by pancreatitis per se.
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As of Dec. 1984 we have been involved in the treatment of 55 patients with acute pancreatitis (gallstone associated, 21; alcoholic, 4; postoperative, 11 and others, 19). An attempt was made to grade these patients according to the severity by modification of Bank's criteria, using seven indices such as shock, respiratory failure, renal failure, metabolic abnormalities, hematological disorders, neurological disturbances and abdominal findings including those obtained intraoperatively. We designated mild, moderate and severe pancreatitis according to the sum total of abnormal criteria above. The mild, moderate and severe pancreatitis have zero, one and more than two abnormal indices, respectively. The severity of the pancreatitis correlated well with the pathological finding of the pancreas, the numbers of other organ failures and mortality rate. The mortality rate during admission of the patients with mild, moderate and severe pancreatitis were four, 14.3 and 70.6%, respectively, the overall mortality rate being 27.2%. Recently, we have introduced plasmapheresis into a new candidate for the treatment of acute severe pancreatitis. Our principle for the management of acute pancreatitis is conservative therapy. However, the patients with moderate and severe pancreatitis need more combined therapeutic interventions with surgery, peritoneal lavage and plasmapheresis if the patients indicate no improvement of severity in spite of intensive conservative treatment.
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Highly purified natural interferon-gamma (IFN-gamma) induced differentiation having characteristics that are associated with the human promyelocytic leukemia cell line, HL-60. Monoclonal antibody to INF-gamma neutralized its activity. However, the natural IFN-gamma had almost no inducing activity in ML-1, a human myeloblastic leukemia cell line. Similar results were obtained using recombinant IFN-gamma. Mitogen stimulated human leukocyte conditioned medium (LCM) induced differentiation of both ML-1 and HL-60 cells. After treatment of LCM with monoclonal antibody to IFN-gamma, LCM activity was reduced more than 50% in ML-1 cells, and 80% in HL-60 cells. Even if IFN-gamma was eliminated from LCM by affinity chromatography, the LCM induced differentiation of ML-1 and HL-60 cells, but IFN-gamma markedly enhanced the ML-1 cell differentiation induced by IFN-gamma free LCM. The results suggest that leukocytes produce differentiation inducing factor(s) other than IFN-gamma, and that IFN-gamma is both an inducer and an enhancer of induction of human myelogenous leukemia cells.
The bindings of ATP to Escherichia coli coupling factor ATPase (F1) and its isolated beta subunit were studied with 8-anilinonaphthalene-1-sulfonate (ANS). The fluorescence of ANS increased upon addition of F1 or the beta subunit, and this fluorescence was quenched on addition of ATP. Thus, ANS bound to the hydrophobic region of F1 or the beta subunit, and the binding of ATP was detected as a quenching of ANS fluorescence. The quenching of the fluorescence suggested that F1 or the beta subunit underwent a conformational change on binding to ATP. With and without ATP, 5.0 and 3.6 mol of ANS, respectively, bound to 1 mol of F1. On the other hand, with or without ATP about 1 mol of ANS bound to beta. The fluorescence quenching was specific for ATP and was not observed with GTP or CTP. It was dependent on pH, being higher at acidic pH, but it was not enhanced by MgCl2. The dissociation constants of F1 and the beta subunit for ATP were estimated to be 10(-4)-10(-5) M. The significance of these binding sites is discussed in relation to the mechanism of the ATPase.
The ability of TPA to induce stable phenotypic changes that normally serve as markers of differentiation was examined in the four human non-T, non-B cell lines, NALL-1, NALM-16, REH and KM-3. In all four lines, noncytotoxic concentrations of the phorbol ester caused an extensive reduction in the number of cells expressing cALL surface antigen and terminal deoxynucleotidyl transferase. The disappearance of these markers correlated with the loss of cell proliferation. In one of the cell lines, NALL-1, TPA treatment gave rise to a significant increase in Ia-like antigen and antigen T-101, markers which represent more advanced stages of cell maturation. However, surface or cytoplasmic immunoglobins, indicators of mature B cells, were not detectable. Antigen 3A1, specific for myeloid and for T cells, antigen Leu-4, specific for T cells and antigen CM1, specific for monocytes, were also absent. In all cell lines, exposure to TPA resulted in an approximately two-fold increase in acid phosphatase and beta-glucuronidase activity. The emergence of these phenotype changes was not altered upon repeated washing of the TPA-treated cells. These results demonstrate that while TPA is capable of inducing various non-T, non-B cell lines to differentiate to a limited degree, differences exist between the lines in the extent to which they can mature towards the B-cell stage.
Increased sympathetic nervous system activity and vasopressin release has been demonstrated in established DOCA-salt hypertension in the rat. To determine the importance of these mechanisms in centrally-mediated pressor responses in this model of hypertension, both awake rats and rats anaesthetised with urethane were given intracerebroventricular injections of carbachol. The systolic blood pressure after implanting a silicon rubber mould containing DOCA, and with subsequent substitution of 1% saline in tap water, increased from 112 +/- 3 mmHg to a stable 188 +/- 7 mmHg by the end of 4 weeks, measured using a tail-cuff method. The blood pressure consistently became elevated when carbachol was injected into the cerebral ventricles of awake rats. Of the three groups of normotensive rats (NTR), sham-operated rats (SHAM) and DOCA-salt hypertensive rats (DOCA), the magnitude of the pressor phase was largest in the DOCA rats. The heart rate in all three groups of rats decreased similarly. When the rats were later anaesthetised with urethane to allow recording of abdominal sympathetic nerve activity, the carbachol injections caused biphasic blood pressure responses and sympathetic nerve discharge consisting of initial vasodepression and sympathetic nerve inhibition of short duration. This was followed by a sustained pressor phase accompanied by a corresponding increase in sympathetic nerve activity. The magnitude of the pressor response was again larger in the DOCA than in the SHAM rats. Spinal section abolished the initial depressor phase but did not much affect the sustained pressor phase.(ABSTRACT TRUNCATED AT 250 WORDS)