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Biomedical subjects

J Rivas

Publications and source records attributed to J Rivas.

At least 55 records · Page 3Linked to original sources

The cytotoxicity of sarcosinamide chloroethylnitrosourea (SarCNU) and BCNU in primary gliomas and glioma cell lines: analysis of data in reference to theoretical peak plasma concentrations in man.

The cytotoxicity of a new compound, sarcosinamide chloroethylnitrosourea (SarCNU), was compared with that of the clinically available bis-chloroethylnitrosourea (BCNU) in 13 primary human gliomas and in 3 human glioma cell lines using the Human Tumor Cloning Assay (HTCA). At concentrations less than or equal to 16 micrograms/ml, SarCNU reduced the growth to less than or equal to 30% of control in 11 of 13 primary gliomas. At similar concentrations, BCNU produced a comparable cytotoxic effect in 6 out of 13 specimens. At concentrations less than or equal to 16 micrograms/ml, BCNU reduced colony growth to less than or equal to 30% of control in all three glioma cell lines and SarCNU produced the same effect in only one glioma cell line. A recently described statistical model, which employs the LD50 dose of new agents in mice, was used to estimate the achievable peak plasma concentration (PPC) of SarCNU. The calculated PPC for SarCNU was found to be 14.8 micrograms/ml compared with 2 micrograms#ml for BCNU. A reevaluation of the cytotoxic activities of SarCNU and BCNU at concentrations approximating their respective PPCs revealed that SarCNU reduced the growth to less than or equal to 30% of control in one cell line at a concentration below its PPC. In contrast, BCNU exhibited similar toxicity in each cell line only at concentrations exceeding its PPC of 2 micrograms/ml. In the case of the primary gliomas, SarCNU was active (less than or equal to 30% of control) in ten tumors at concentrations less than or equal to 14.8 micrograms/ml, whereas BCNU was active in only one glioma at a concentration less than or equal to 2 micrograms/ml. The results suggest that SarCNU should be more active than BCNU against human gliomas, provided that the statistical model used has correctly estimated the PPC of SarCNU.

Carmustine↗

Continuous respiratory support in quadriplegic children by bilateral phrenic nerve stimulation.

Three children, aged 6-10 years, in whom cervical cord injury at the C1-C2 level resulted in apnoea had bilateral implantation of diaphragm pacemakers. With periods of gradual conditioning of the diaphragm muscle to low frequency stimulation and slow respiratory rates they adapted to continuous ventilatory support by simultaneous stimulation of both hemidiaphragms without evidence of fatigue, so far for periods of 23-47 months.

Apnea↗

Purification and properties of glutathione reductase from the cyanobacterium Anabaena sp. strain 7119.

An NADPH-glutathione reductase (EC 1.6.4.2) has been purified 6,000-fold to electrophoretic homogeneity from the filamentous cyanobacterium Anabaena sp. strain 7119. The purified enzyme exhibits a specific activity of 249 U/mg and is characterized by being a dimeric flavin adenine dinucleotide-containing protein with a ratio of absorbance at 280 nm to absorbance at 462 nm of 5.8, a native molecular weight of 104,000, a Stokes radius of 4.13 nm, and a pI of 4.02. The enzyme activity is inhibited by sulfhydryl reagents and heavy-metal ions, especially in the presence of NADPH, with oxidized glutathione behaving as a protective agent. As is the case with the same enzyme from other sources, the kinetic data are consistent with a branched mechanism. Nevertheless, the cyanobacterial enzyme presents three distinctive features with respect to that isolated from non-photosynthetic organisms: (i) absolute specificity for NADPH, (ii) an alkaline optimum pH value of ca. 9.0, and (iii) strong acidic character of the protein, as estimated by column chromatofocusing. The kinetic parameters are very similar to those found for the chloroplast enzyme, but the molecular weight is lower, being comparable to that of non-photosynthetic microorganisms. A protective function, analogous to that assigned to the chloroplast enzyme, is suggested.

Amino Acids↗

Bioelectrical tissue resistance during various methods of myocardial preservation.

Twenty-one mongrel dogs underwent cardiopulmonary bypass (CPB) and ischemic cardiac arrest for 60 minutes. The bioelectrical tissue impedance, water content, and ultrastructure of the myocardium were studied and correlated with various types of myocardial protection applied. The animals were divided into three groups according to the myocardial protection applied: Group 1, moderate general hypothermia; Group 2, moderate general and local hypothermia; Group 3, moderate general hypothermia and crystalloid cardioplegia. The hearts from 3 normal dogs served as controls. After 35 minutes of ischemic arrest, the difference in bioelectrical impedance of the myocardium of the left ventricle between Groups 1 and 2 was highly significant (p less than 0.001); in Groups 2 and 3, a significant difference was observed after 50 minutes. The heart water content in all three groups increased over that found in the hearts of the control animals, but there was no significant difference between Groups 2 and 3. There was evidence by ultramicroscopic study of ischemic damage to the myocardium in all of the experimental groups. Damage was less evident in Groups 2 and 3. We conclude that measurement of myocardial bioelectrical tissue resistance is a sensitive indicator of myocardial damage due to ischemia and may be useful clinically in determining the need for and type of cardiac resuscitation, particularly following CPB.

Animals↗

Technical advances in the Senning operation.

Since March 1978, 59 patients with transposition of the great arteries (TGA) ranging in age from 2 months to 6 years have undergone the Senning operation. Forty-six patients (77.9%) had transposition with intact ventricular septum, 8 of them with patent ductus arteriosus; 8 patients (13.5%) had TGA with ventricular septal defect (VSD), 3 of them with previously performed banding; 4 patients (6.7%) had TGA with VSD and pulmonary stenosis (PS), and one (1.6%) had TGA with PS. Prior to correction, 38 cases had undergone a Rashkind septotomy and 15 had had a previous Blalock-Hanlon septectomy. During this time we have introduced some technical modifications of the original Senning operation: (A) right atrial incision, (B) large left atrial wall window, (C) infrasinal suture of the left atrial flap, (D) avoidance of damage to the hypothetical anterior atrioventricular conduction bundle, and recently, in 12 patients, we have used (E) an inverted left atrial appendage as an interatrial flap. There were 9 hospital deaths (15.2%) caused by low cardiac output (4 cases), severe hypoxemia and low cardiac output (4 cases) and one patient with pulmonary venous drainage obstruction died following reoperation. Two patients developed neurological complications that disappeared without sequela. Another complication was a right chylothorax (4 patients), which improved without the necessity of surgical repair. Eighteen patients developed a junctional rhythm for a period over 24 hours. We think that the technical modifications which we present here, partially contribute to improving the Senning operation.

Cardiac Output, Low↗

Points to consider when choosing a biopsy method in cases of pleurisy of unknown origin.

Blind pleural needle biopsy and diagnostic thoracoscopy are procedures sometimes used in the work-up of a patient with pleural effusion of unknown origin. We reviewed 203 diagnostic thoracoscopies in patients with malignant pleural effusion to show the different location of pleural metastasis, some out of the reach of blind needle biopsy. Based on these data, we find diagnostic thoracoscopy a superior procedure because of its higher reliability, faster diagnostic results, slight or no complications, and the possibility of carrying out pleurodesis in the same examination.

Biopsy, Needle↗

Specific modification of gastric K+-stimulated ATPase activity by thimerosal.

Treatment of hog gastric microsomes with the sulfhydryl reagent, thimerosal (ethylmercurithiosalicylate), produced differential effects on the K+-ATPase and the K+-stimulated p-nitrophenylphosphatase activities. For example, exposure to 2 mM thimerosal for 3 min severely reduced the activity of K+-stimulated ATPase, while K+-p-nitrophenylphosphatase activity was enhanced 2- to 3-fold. Higher concentration of thimerosal, or longer incubation times, also led to inhibition of K+-p-nitrophenylphosphatase. The activated state of p-nitrophenylphosphatase could be sustained by a 20-fold, or greater, dilution of treated membranes, and could be reversed by reduction of membrane SH groups by exogenous thiols. Significant activation of K+-p-nitrophenylphosphatase was not produced by p-chloromercuribenzene sulfonate, p-chloromercuribenzoate or mersalyl; however, ethyl mercuric chloride had qualitatively similar activity effects as thimerosal. Kinetics of K+-p-nitrophenylphosphatase for thimerosal-treated membranes were altered as follows: V increased; Km for p-nitrophenylphosphate unchanged for Ka for K+ increased. ATP, which is a potent inhibitor of K+-p-nitrophenylphosphatase activity in native membranes (KI approximately 200 microM). These data suggest that there are multiple SH groups which differentially influence the gastric K+-stimulated ATPase activity. Defined treatments with thimerosal are interpreted as an uncoupling of the K+-stimulated phosphatase component of the enzyme (for which p-nitrophenylphosphatase is a presumed model reaction). Such differential modifications can be usefully applied to the study of partial reactions of the enzyme and their specific role in the related H+-transport reaction.

4-Nitrophenylphosphatase↗

Assimilatory nitrate reductase from Acinetobacter calcoaceticus.

A soluble nitrate reductase from the bacterium Acinetobacter calcoaceticus grown on nitrate has been characterized. The reduction of nitrate to nitrite is mediated by an enzyme of 96000 molecular weight that can use as electron donors either viologen dyes chemically reduced with dithionite or enzymatically reduced with NAD(P)H, through specific diaphorases which utilize viologens as electron acceptors. Nitrate reductase activity is molybdenumdependent as shown by tungstate antagonistic experiments and is sensitive to--SH reagents and metal chelators such as KCN. The enzyme synthesis is repressed by ammonia. Moreover, nitrate reductase activity undergoes a quick inactivation either by dithionite and temperature or by dithionite in the presence of small amounts of nitrate. Cyanate prevents this inactivating process and can restore the activity once the inactivation had occurred, thus suggesting that an interconversion mechanism may participate in the regulation of Acinetobacter nitrate reductase.

Acinetobacter↗