Search PubMedSearch

Biomedical subjects

C Rodriguez

Publications and source records attributed to C Rodriguez.

At least 55 records · Page 3Linked to original sources

Tumor necrosis factor expression in human epithelial tumor cell lines.

Tumor necrosis factor (TNF) is a monokine with in vitro cytotoxicity for some but not all tumor cells. The basis for sensitivity and resistance to the antitumor effects of this agent remains unclear. The present studies have monitored the effects of TNF on 14 epithelial tumor cell lines. Eleven of these cell lines were resistant to the growth inhibitory effects of TNF (50% inhibitory concentration greater than 1,000 U/ml). 12 of the 14 tumor cell lines has detectable levels of high affinity cell surface TNF binding sites, thus suggesting that resistance was not often due to the absence of cell surface TNF receptors. Northern blot analysis demonstrated that three of the eleven resistant cell lines expressed detectable levels of TNF mRNA. Furthermore, both sensitive and resistant epithelial tumor cells had the capacity to express TNF transcripts in the presence of the protein synthesis inhibitor, cycloheximide. Finally, the presence of TNF expression at the RNA level is shown to be associated with the production of a TNF-like protein in the resistant Ov-D ovarian carcinoma cells. These findings suggest that certain human epithelial tumor cell lines inherently resistant to TNF also express this cytokine.

Animals

Impaired production and lack of secretion of interleukin 1 by human breast milk macrophages.

Interleukin 1 (IL-1) production by human breast milk macrophages (HMMø) in response to bacterial lipopolysaccharides (LPS) was investigated in 49 healthy mothers and compared with that of blood monocytes (HMo). IL-1 activity in 24 h HMMø culture supernatants was in most cases below the assay detection limits and much smaller than that of stimulated HMo (72 +/- 17 u/ml). Intracellular IL-1 activity in response to LPS in HMMø raised from less than 2 +/- 1 u/ml to 19 +/- 12 u/ml and was similar to that found in stimulated HMo (16 +/- 4 u/ml). Neither the low IL-1 production by HMMø nor its release into supernatants could be increased by stimulating with higher LPS concentrations (40-400 micrograms/ml) or when longer culture times were assayed (24-72 h). Inhibiting the production of prostaglandins by adding indomethacin to HMMø cultures, caused no effect either on IL-1 production or on its secretion to supernatants. The presence of inhibitors for the IL-1 thymocyte proliferative assay, in supernatants from HMMø, was excluded by mixing experiments with a known amount of IL-1. Thus, we conclude that HMMø produce four or five times less IL-1 than HMo in response to LPS stimulus. Furthermore, HMMø are completely unable to release the IL-1 produced.

Adolescent

Liquid-chromatographic determination of free and total 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol in urine.

We describe the conjoint measurement in urine of the alcoholic catecholamine metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG). The method involves extraction with ethyl acetate and back-extraction into acetic acid (MHPG), followed by adsorption onto alumina (DHPG). The separation is performed by reversed-phase liquid chromatography with column switching and amperometric detection. Total (free plus conjugated) compounds are determined after a 24-h enzymatic hydrolysis. Twelve-hour excretion values for normal and hypertensive subjects are given, together with results obtained for patients with pheochromocytoma, chemodectoma, and congenital dopamine-beta-hydroxylase deficiency. The assay is sensitive, reproducible, and free of interferences, and may lead to a better understanding of overall catecholamine metabolism in health and disease.

Adrenal Gland Neoplasms

Miliary tuberculosis and adult respiratory distress syndrome.

Although, miliary tuberculosis is an unusual cause of severe acute respiratory failure, we describe nine patients with miliary tuberculosis who developed adult respiratory distress syndrome. This complication occurred in seven patients despite treatment with antituberculous drugs. In two patients who developed the syndrome, miliary tuberculosis was diagnosed only at postmortem. The presence of pulmonary hypertension in all cases and disseminated intravascular coagulation in seven cases suggests a possible pathophysiologic relationship with severe pulmonary vascular damage. The high mortality rate (88.8%) was associated with nonpulmonary organ system failure. Miliary tuberculosis should be considered in patients with adult respiratory distress syndrome of unknown etiology, and simple diagnostic procedures such as sputum, bronchial brushing, and gastric examination should be followed by invasive diagnostic procedures to confirm this etiology. Since untreated miliary tuberculosis is usually fatal, early recognition of this disease is of great importance, and specific therapy may play a lifesaving role.

Adult

Induction of tumor necrosis factor expression and resistance in a human breast tumor cell line.

Tumor necrosis factor (TNF) is a polypeptide cytokine that is cytotoxic to some but not all tumor cells. The basis for resistance to the cytotoxic effects of this agent remains unclear. We have studied the development of TNF resistance in human ZR-75-1 breast carcinoma cells. ZR-75-1 cells have undetectable levels of TNF RNA and protein. However, TNF transcripts are transiently induced in these cells by exposure to recombinant human TNF. This induction of TNF RNA is associated with production of TNF-like protein in cell lysates and culture supernatants. Stable resistance to TNF-induced cytotoxicity develops when ZR-75-1 cells are exposed to increased concentrations of TNF. The TNF-resistant cells, designated ZR-75-1R, continuously express TNF transcripts and a TNF-like protein. Furthermore, ZR-75-1R cell supernatants contain cytotoxic activity that is abrogated by polyclonal antibody against TNF. The ZR-75-1R cells also possess TNF receptors that are occupied or down-regulated by the TNF-like protein. These findings thus suggest that (i) TNF induces TNF transcripts and production of a TNF-like protein in ZR-75-1 cells and (ii) resistance to TNF-induced cytotoxicity is associated with stable TNF expression.

Breast Neoplasms

Routine analysis of catecholamines and metabolites in urine by a liquid chromatographic column switching system.

A reversed-phase liquid chromatographic technique including a column switching system has been adapted for the routine measurement of catecholamines and their metabolites (14 compounds) in urine. From 1 ml of urine all the compounds and the internal standards were obtained according to combined extraction procedures involving organic solvent, anionic and weakly cationic resins. Finally four extracts (catecholamines, methoxamines, acidic and neutral derivatives) had to be chromatographed throughout a wholly automated apparatus. For each run, the column switching system determined the analytical columns to be used to obtain the separation of the compounds from interferences due to other co-extracted endogenous substances, while the analysis times remained between 20 and 40 min. Such a system allowed the rapid clean-up of columns (in direct- and back-flush mode) carried out between two consecutive injections. By coupling on-line fluorimetric and electrochemical detections the specificity of the technique could be checked, since the ratio of the responses of both detectors was an index of the purity of the peaks. Finally the advanced automation of the equipment allowed weekly the evaluation of catecholamines and the whole range of their known metabolites in 36 urine samples.

Catecholamines

Effects of calcium channel blockers on gastric emptying and acid secretion of the rat in vivo.

Experiments were designed to evaluate the effects of three calcium channel blockers (verapamil, diltiazem and cinnarizine) on gastric emptying and secretion in the rat. Pretreatment with the calcium blockers delayed gastric emptying of phenol red in a dose-dependent manner. Verapamil was the most effective of the agents tested. Verapamil and diltiazem inhibited gastric acid secretion in the pylorus-ligated rat without affecting pepsin output. Cinnarizine was ineffective in this model. When the perfused lumen of the anaesthetized rat was used, verapamil was found to inhibit responses to carbachol or histamine more than those to pentagastrin. Further, we found a greater sensitivity to verapamil for basal compared with vagal-stimulated (2-deoxy-D-glucose) acid secretion. Neither diltiazem nor cinnarizine modified gastric acid secretion in this experimental model. These findings are discussed in relation to the role of extracellular calcium in gastric motility and secretion, and the existence of a regional and functional selectivity for calcium blockers is proposed.

Anesthesia

Bioenergetic and cardiovascular responses to exercise in residents at 2.850 m, with asymptomatic Chagas' disease.

Cardiovascular and energetic responses at rest, during 30 min of exercise (mechanical output: 125 watts) and for a subsequent recovery period of 5 min were compared in two groups, each comprising 21 residents at an altitude of 2.850 m. One group was in the asymptomatic phase of Chagas' disease with positive serological tests for T. cruzi, whereas the other was without Chagas' disease (negative serological tests). The two groups were similar as regards age, weight-for-height, blood parameters, nutritional status and heart and lung functions, including heart rate and frontal plane QRS axis determinations. At rest, they differed in that maximal and minimal arterial blood pressures were slightly but significantly lower in the group with Chagas' positive serological tests than in the controls. During exercise and recovery, the only differences between them and the controls were that their minimal diastolic arterial blood pressure was significantly lower. In absolute values, the rises in arterial pressure due to exercise were exactly the same in the two groups. Maximal O2 uptake was identical in both groups, as was exercise steady state VO2. These findings indicate that the asymptomatic subjects with Chagas' disease had a normal work capacity and were not affected by high altitude.

Adult

Turbidimetry of rheumatoid factor in serum with a centrifugal analyzer.

We describe the simple, rapid turbidimetry of IgM rheumatoid factor in human serum by use of the Cobas-Bio centrifugal analyzer. Heat-aggregated human IgG is used as the antigen. The immunoturbidimetric reaction is monitored at 340 nm for 300 s, and the changes in absorbance after the antigen is added are used to prepare the standard curve. Test results are calculated from the stored curve and reported in int. units/mL, based on comparison with the WHO reference serum for rheumatoid factor. There is no interference from bilirubin (up to 340 mumol/L) or hemoglobin (up to 5600 mg/L). Serum samples with a triglyceride concentration greater than 2.20 mmol/L must be cleared of lipids before analysis. The standard curve is linear from 30 to 500 int. units/mL. Precision, accuracy, linearity, and sensitivity are quite acceptable. The CV was generally less than 5% for different concentrations of rheumatoid factor. Results agree well with those by a rate-nephelometric procedure on the Beckman ICS system (rs = 0.932). However, both correlate poorly with a modified classical Waaler-Rose test. Of 47 patients with rheumatoid arthritis, 34 had IgM rheumatoid factor in their serum, but the measured value did not reflect the activity of the disease.

Adult

Measurement of urinary catecholamines and their catechol metabolites and precursor by liquid chromatography with column-switching and on-line fluorimetric and electrochemical detection.

A new method is described for the determination of catecholamines and their precursor (3,4-dihydroxyphenylalanine), and separately of their catechol metabolites (3,4-dihydroxymandelic acid, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethylene glycol and 3,4-dihydroxyphenylethanol) in urine. After a two-step pretreatment involving ethyl acetate extraction and adsorption onto alumina, the separation is performed by ion-pair reversed-phase high-performance liquid chromatography. A column-switching system enables complete separation of the most polar compounds without increase in the total analysis time. The column eluates are monitored with both fluorimetric and amperometric detectors, the relative responses of which are used as an index of peak purity. Reference values for twelve healthy adults are given.

Adult

Major surface protein of Toxoplasma gondii (p30) contains an immunodominant region with repetitive epitopes.

Four monoclonal antibodies (mAb) against surface antigens of tachyzoites of Toxoplasma gondii were produced. Immunoprecipitation of extracts of 125I-labeled tachyzoites identified the same polypeptide with apparent molecular weight of 30 000 (p30). A competition binding assay indicated that a single region of p30 was recognized by all 4 of the mAb. Furthermore, we found that single mAb inhibited 25-50% of the specific binding of antibodies of patients with toxoplasmosis to the antigenic extract of tachyzoites. It appears, therefore, that p30 is the most immunogenic constituent of tachyzoites, and that a single region of this molecule contains most of the immunogenic activity. Finally, a two-site/one-antibody immunoradiometric assay with the same mAb indicated that the p30 molecule is multivalent with respect to the expression of a single epitope.

Animals

Toxoplasma gondii: redistribution of monoclonal antibodies on tachyzoites during host cell invasion.

Immunodetection of protein P30, a major surface antigen of Toxoplasma gondii tachyzoites, by a specific monoclonal antibody has demonstrated a homogenous distribution of this antigen on the surface of intra- and extracellular tachyzoites at all stages of their endodyogenic development. On living zoites, no redistribution of anti-P30 was obtained, contrasting with the capping obtained with antiserum to T. gondii. Upon invasion of a host cell, however, most of the coat of anti-P30 was shed from preincubated zoites at the level of the moving junction governing the entry of the parasite into the host cell.

Animals

Influence of hormones and undernutrition on brain development in newborn rats.

High L-thyroxine (T4) and cortisol doses given to rats during the first 8 days of life and on the first day only respectively, produce decrease of body and brain weight and perturbances to brain energy substrates, i.e. glucose and ketone bodies. The same alterations are found in the undernourished rats from the prenatal period. The pituitary GH and TSH is decreased in the T4- and cortisol-injected animals. The plasma ACTH is decreased in the treated cortisol animals at 8, 12 and 22 days of life. The pituitary TSH content is reduced with respect to controls in the undernourished animals from 14 to 70 days of life. From the exposed experiments we suggest an alteration in the hypothalamic-pituitary complex in T4- and cortisol-treated rats, and describe the similarities between the three experimental models.

Aging

Anaprox in dysmenorrhea: reduction of pain and intrauterine pressure.

In a double-blind parallel trial, 24 dysmenorrheic women received a single dose of Anaprox (1,100 mg) or placebo. Over the next 2 hours, pain intensity was scored and intrauterine pressure was measured using an immobilized microballoon. At the end of 2 hours, all 11 patients given Anaprox (but only three of the 13 given placebo) experienced complete pain relief (p = 0.0004). The resting intrauterine pressure (IUP) decreased from a mean of 51.4 to 26.8 mm Hg in the Anaprox-treated group, while in the placebo group the mean resting IUP values remained essentially unchanged ( drop from 55.4 to 51.9 mm Hg was observed). This difference between the two treatment groups was statistically significant in favor of Anaprox (p = 0.03). Several patients from each group were given 0.2 mg of ergonovine by intramuscular injection following the 2 hour trial. In both groups, the resting IUP increased within 30 minutes; the corresponding increase in pain intensity was more pronounced, however, in the placebo group. These results support the premise that a decrease in resting IUP is directly linked to the pain-relieving effects of Anaprox.

Adolescent

Purification and partial characterization of an antibiotic produced by Myxococcus coralloides.

A strain of Myxococcus coralloides producing an antibiotic capable of inhibiting growth of Gram-positive bacteria was isolated. Antibiotic production occurred during vegetative growth but not during myxospore formation. The antibiotic was extracted from the growth medium with chloroform and purified by adsorption on silicic acid and by preparative silica gel thin-layer chromatography. The purified antibiotic showed a resistance to heat, acid, alkali and proteolytic enzymes. Chromatographic and electrophoretic behavior as well as infrared, ultraviolet and mass spectra are presented.

Anti-Bacterial Agents