Atomic-weight dependence of the production of hadron pairs by 800-GeV/c protons on nuclear targets.
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Journal Article↗
Biomedical subjects
F Lopez
Publications and source records attributed to F Lopez.
Modalities of synthesis of Ki67 antigen during the stimulation of lymphocytes.
The antibody Ki67 is currently used to evaluate the proliferative fraction of solid tumors and some hematological malignancies. We have used phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes as a model to study the entry of quiescent cells into cell cycle and to follow their progress to the next cycle. Flow cytometric analysis of lymphocyte samples stained with the antibody Ki67 and a DNA marker has allowed us to follow the expression of Ki67 antigen (Ki67 Ag) as a function of the position of the cells in the cell cycle. The use of drugs blocking the stimulated lymphocytes in different phases of the cell cycle permitted us to demonstrate that Ki67 Ag expression started from the beginning of the first S phase. The level of Ki67 Ag increased during S phase until mitosis, when its expression was maximal. After division, the cells in G1 phase showed a decrease in Ki67 Ag expression (possibly corresponding to degradation) until they reentered S phase, when the level of Ki67 Ag increased again. The results confirm that the expression of Ki67 Ag is related to the proliferative state of the cells and suggest that it may be used to determine the proliferative cell fraction in hematopoietic tissues.
Antigens, Surface↗
High dose rate intracavitary radiation therapy of carcinoma of the cervix using a linear source.
One hundred patients with carcinoma of the cervix stages 1B to 4A were treated with intracavitary high dose rate radiation using a linear cobalt source. All cases have received external beam pelvic irradiation to 4500cGy mid plane in twenty fractions over four weeks. The results in terms of patient compliance and convenience were good while acute and late morbidities were comparable to standard Manchester technique of low dose rate intracavitary therapy as practised in the Institute of Radiotherapy and Oncology General Hospital Kuala Lumpur. The four year actuarial survival rate is 76% for stage II and 48% for stage III. All three stage IV patients died within 1 year. Four out of seven stage I patients are alive (minimum follow-up 18 months, longest 43 months). One died of systemic spread at 33 months while one is lost to follow up.
Adult↗
Effects of intracarotid and intravenous infusion of human TNF and LT on established intracerebral rat gliomas.
The effects of recombinant human tumor necrosis factor (TNF) and lymphotoxin (LT) were investigated against two different established rat gliomas. Single preestablished intracarotid (ic) or intravenous (iv) doses (1.5-2.0 x 10(6) units) were administered to Wistar rats with intracerebral C6 gliomas and Fischer 344 rats with intracerebral T9 gliomas. Five days after cytokine treatment, animals were sacrificed and tumor size determined by histopathologic techniques. In Wister rats, ic TNF produced a greater reduction in size of C6 tumors than iv TNF. Experiments with Fischer rats showed that both TNF and LT were more effective when administered ic compared to iv. Furthermore, LT induced a greater reduction in tumor size than TNF. Additional studies on the age-related susceptibility of these gliomas revealed early, 8-day tumors were more sensitive to ic LT than advanced, 14-day tumors. No direct toxicity of these cytokines against the tumor cells was detected in vitro indicating their autitumor effect was mediated by alternate mechanisms in vivo. Thus for regionally confined gliomas ic therapy was superior to iv therapy and LT was more effective than TNF. Cytokine treatment was most effective on earlier tumors and there appeared to be differences in efficacy related to the tumor-host combination.
Animals↗
Physiologically important role for central oxytocin in the preovulatory release of luteinizing hormone.
Recently, our laboratory has provided evidence for a physiologically relevant stimulatory influence of oxytocin (OXY) on the preovulatory luteinizing hormone (LH) surge in cycling female rats. The present study evaluated whether this stimulatory effect of OXY on LH release is exerted at a central or peripheral site of action by comparing the ability of peripheral (intravenous) or central (intracerebroventricular) administration of OXY antisera to influence the preovulatory LH surge. The peripheral injection of a very large dose of OXY antisera (0.8 ml) caused a slight attenuation of the early stages of the LH surge. In contrast, the central administration of 5 microliters of OXY antisera completely abolished the preovulatory LH surge. The data support the hypothesis that OXY exerts a physiologically important stimulatory influence on the preovulatory LH surge which is mediated primarily at a central site of action.
Animals↗
Chronic morphine administration augments benzodiazepine binding and GABAA receptor function.
Behavioral and neurochemical evidence indicates links between the opioid and GABA neurotransmitter systems. To assess effects of chronic opiates on the major site of postsynaptic GABAergic activity, the GABAA receptor, we administered chronic morphine and naltrexone to mice and evaluated binding at the benzodiazepine and t-butylbicyclophosphorothionate (TBPS) sites and GABA-dependent chloride uptake. After morphine (3 days), benzodiazepine receptor binding in vivo but not in vitro was increased in cortex compared to placebo-treated mice. TBPS binding was unchanged in cortex, but muscimol-stimulated chloride uptake was increased at low doses of muscimol. Benzodiazepine and TBPS binding and muscimol-stimulated chloride uptake were unchanged in naltrexone-(8 days) compared to placebo-treated mice. When naltrexone was administered previously to block opiate sites, the increases in benzodiazepine binding and chloride uptake observed with chronic morphine were reversed. These results indicate that chronic morphine but not naltrexone enhances benzodiazepine binding and GABAA receptor function, perhaps by an action at opioid receptors.
Animals↗
Chronic administration of benzodiazepines--V. Rapid onset of behavioral and neurochemical alterations after discontinuation of alprazolam.
Discontinuation of chronic treatment with alprazolam may cause a characteristic clinical syndrome. To assess the basis of this syndrome, mice were treated with alprazolam, 2 mg/kg, for 7 days, a regimen associated with the development of tolerance and downregulation of receptors. Effects on motor activity and the binding and function of GABA receptors were evaluated 1, 2, 4 and 7 days after discontinuation. Motor activity was similar to controls 1 day after cessation of alprazolam, increased from days 2 to 4 after-alprazolam, and returned to control values by 7 days. The binding of benzodiazepines in vivo and in vitro was increased in the cortex 2 and 4 days after alprazolam and in the hypothalamus at 4 days after alprazolam. Binding returned to control values in all areas by 7 days. Binding at the chloride channel, using [35S]t-butylbicyclophosphorothionate, was not significantly altered after discontinuation. Muscimol-stimulated uptake of [36Cl-] in cortical synaptoneurosomes was increased at 4 days after alprazolam, compared to days 1, 2 and 7. Thus, behavioral and neurochemical alterations was associated with the discontinuation of alprazolam. These alterations were qualitatively similar to those observed following discontinuation of lorazepam but occurred more rapidly and with differing regional specificity.
Alprazolam↗
Molecular basis of the association of arterial proteoglycans with low density lipoproteins: its effect on the structure of the lipoprotein particle.
Modifications of low density lipoproteins (LDL) that enter the arterial intima appear to be responsible for their eventual extracellular and intracellular accumulation during atherogenesis. Some of these modifications seem to be the result of LDL association with intimal chondroitin sulphate-rich proteoglycans (CSPG). We have used frontal elution affinity chromatography, binding and competition experiments with synthetic segments of apoB-100 to better define the ligand regions for the LDL-CSPG complexes. The minimum structural requirement for recognition by the CSPG appears to be a hydrophilic nine-residue amino-acid segment with five lysine and arginine residues. Analysis of other similar regions in apoB-100 and other glycosaminoglycan-binding proteins suggest that besides a cluster of positively charged amino-acids, the presence of hydroxyl-containing residues favours the association with sulphated proteoglycans. With controlled proteolytic hydrolysis, we found that the interaction of LDL with CSPG modifies the surface accessibility of a apoB-100 segments containing arginine and lysine. Because these apoB-100 domains may also be involved in cell-receptor binding, the CSPG-induced modifications could be the structural explanation for the observed increase in cellular uptake of proteoglycan-modified LDL.
Amino Acid Sequence↗
Hepatitis B in a highly active prostitute population: evidence for a low risk of chronic antigenemia.
The epidemiology of hepatitis B in female prostitutes was studied in a cross-sectional survey of 467 prostitutes and 510 control prenatal clinic patients from Lima and Iquitos, Peru. Prostitutes reported a mean of 8.8 +/- 6.7 years of active prostitution and a mean of 205 +/- 137 sexual contacts in the month prior to the study. Hepatitis B surface antigen (HBsAg) was found in comparable percentages of prostitutes (1.7%) and controls (0.8%; P = .305). In contrast, seropositivity for both antigen and antibody markers (HBsAg, anti-HBs, or anti-hepatitis B core) was found in a significantly higher percentage of prostitutes than controls (67.0% vs. 10.0%; P less than .0001). By multivariate analysis, both prostitution (odds ratio [OR] 14.6) and the number of years of exposure as a prostitute (OR 3.2 for 10 years of exposure at age 35 years) were significantly associated with seropositivity for hepatitis B markers when adjusted for age. In this study, the prevalence of HBsAg was not substantially increased in highly active female prostitutes compared with the general population, even though hepatitis B transmission was greatly increased. These data suggest that in adult women with a high level of hepatitis B infection, hepatitis B antigenemia may not persist as frequently as previously indicated in studies of other populations.
Adult↗
Acute treatment with clonidine or calcium entry blockers on opioid withdrawal in guinea-pig ileum.
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Animals↗
[Adolescence and contraception: 1. A study knowledge and use among women hospitalized for childbirth or abortion].
A study of the knowledge and utilization of contraceptive methods by adolescent is presented. An analysis was carried out based on data collected from interviews with and recorded case histories of 78 puerperal adolescents (childbirth or abortion), assisted by an obstetric service in the county of Cotia, SP, Brazil, between May 1 and July 31, 1986. Of all the adolescents studied, 61.5% had some knowledge of contraceptive methods; the findings showed that such knowledge was influenced by factors such as: age, school background, parity and marital status. The main sources of information on contraception were: friends, relatives and partners, in this order; those least sought for in this regard were health professionals. Only one in each ten adolescents made use of some contraceptive measure, the most prevalent methods being the contraceptive pill, the Ogino-Knauss method, condoms and coitus interruptus. In all of the cases of the utilization of these methods the same had been "recommended" by persons belonging to the adolescents' social group, and had been acquired in shops, without any health control.
Adolescent↗
Chronic benzodiazepine administration: effects in vivo and in vitro.
Chronic benzodiazepine administration is associated with neurochemical alterations in the GABAergic system, as determined in a variety of animal models and tissue culture systems. In animals, effects of chronic benzodiazepine agonists on receptor binding are uncertain, but several studies indicate a decrease in GABA-dependent chloride uptake. In contrast, limited data indicate that chloride uptake is increased after chronic antagonist administration, and results of inverse agonist administration are uncertain. Most animal studies are limited by lack of attention to drug choice and to pharmacokinetic variables, and by failure to determined delivered drug concentrations. More limited data in tissue culture systems are conflicting with regard to effects on benzodiazepine binding, but recent studies indicate that GABA-dependent chloride uptake may be decreased after chronic agonist exposure, and increased after chronic antagonist and inverse agonist administration. Data from these systems may complement results obtained in intact animals, and cultures may allow more detailed examination of the kinetics and specificity of drug effects.
Animals↗
Differential uptake of proteoglycan-selected subfractions of low density lipoprotein by human macrophages.
Macrophages and arterial chondroitin sulfate proteoglycans (CSPG) are probably associated with extracellular and intracellular lipoprotein deposition during atherogenesis. We found that human arterial CSPG can be used to select subclasses from low density lipoprotein (LDL) with different structural properties and capacities to interact with human monocyte-derived macrophages (HMDM). Four subclasses, LDL(PG)1 to LDL(PG)4, in order of decreasing CSPG-complexing capacity, were prepared and characterized in terms of their ability to interact with HMDM. The LDL subclasses with highest avidity for CSPG, LDL(PG)1 and LDL(PG)2, were bound, internalized, and degraded more efficiently than those of lower avidity for CSPG. From LDL(PG)1 to LDL(PG)4, the gradual decrease in uptake by HMDM and decreasing avidity for CSPG were associated with a gradual decrease in isoelectric point (from 5.93 to 5.68) and an augmented ratio of surface polar lipid to core nonpolar components (from 0.35 to 0.54). Competition experiments indicated that the proteoglycan-selected subfractions shared the binding sites and uptake mechanisms of native LDL. The results suggest the existence of a structurally related gradation in the avidity of LDL subpopulations for cells and matrix components. The presence within LDL subpopulations of a differential capacity to interact with intimal extracellular and cellular elements could be associated with a similar heterogeneity in their atherogenic potential.
Binding Sites↗
[Polyradiculoneuritis, rhombencephalitis and encephalitis disclosing legionellosis in a healthy adult].
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Adolescent↗
Interaction of caffeine with the GABAA receptor complex: alterations in receptor function but not ligand binding.
Behavioral and neurochemical evidence indicates interactions between caffeine and other adenosine receptor ligands and the gamma-aminobutyric acid (GABA)-benzodiazepine system. To assess the effects of caffeine on binding and function at the GABAA receptor, we studied the effects of behaviorally-active doses of caffeine on benzodiazepine and Cl- channel binding and on overall function of the GABAA receptor as measured by Cl- uptake. There was no effect of caffeine on benzodiazepine receptor binding in cortical synaptosomal membranes at concentrations of 1-100 microM. No effects on benzodiazepine binding were found ex vivo in mice treated with caffeine, 20 and 40 mg/kg. At the putative Cl- channel site labeled by t-butylbicyclophosphorothionate (TBPS), binding was unchanged in vitro after caffeine treatment (1 and 10 microM) in washed and unwashed membranes. However, in ex vivo studies caffeine (20 and 40 mg/kg) increased numbers of TBPS sites in unwashed but not washed membranes. Muscimol-stimulated Cl- uptake into cortical synaptoneurosomes was decreased in mice treated with caffeine, 20 and 40 mg/kg. Similar results were observed in in vitro preparations treated with 50 microM but not 100 microM caffeine. These results indicate that caffeine administration significantly alters the Cl- transport function of the GABAA receptor complex.
Animals↗
Chronic benzodiazepine administration. IV. Rapid development of tolerance and receptor downregulation associated with alprazolam administration.
The triazolobenzodiazepine compound alprazolam may have unique clinical effects compared to other benzodiazepines, and both behavioral and neurochemical studies have indicated unusual results after acute doses of alprazolam. To determine the effects of chronic dosage in mice, alprazolam (2 mg/kg/day) was administered via osmotic pumps for 1-14 days, and open-field activity, plasma and brain concentrations, benzodiazepine receptor binding in vivo and in vitro, [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding, and muscimol-stimulated chloride uptake were determined. Alprazolam decreased motor activity after 1 and 2 days, but tolerance developed by day 4 and persisted to day 14. Plasma and brain concentrations remained constant during the 2-week period. Benzodiazepine receptor binding in vivo was decreased at day 4 compared to day 1 in cortex (CX) and hypothalamus (HYPO), and remained depressed to day 14 in CX but not HYPO. Benzodiazepine binding in vitro and [35S]TBPS binding were decreased in CX at day 7. Muscimol-stimulated [36Cl-] uptake was decreased at days 4 and 7 compared to day 1, but at day 14 uptake was similar to day 1. These results indicate that behavioral tolerance and receptor downregulation develop rapidly during chronic alprazolam administration. Behavioral and neurochemical changes were similar to those associated with lorazepam administration, but occurred more rapidly and with different regional specificity.
Alprazolam↗
Binding parameters and concentration modulate formation of complexes between LDL and arterial proteoglycans in serum.
The interactions of LDL with extracellular matrix proteoglycans apparently contribute to the accumulation of apo B-lipoproteins in atherogenesis. Serum LDL forms insoluble complexes with human arterial chondroitin sulfate proteoglycans (CSPG). While the amount of insolubilized LDL varies, serum from survivors of myocardial infarcts and ischaemic subjects shows higher values of CSPG-insolubilized LDL than serum from controls. In this study, we explored the relationship between the formation of LDL-CSPG complexes in serum and some LDL properties, using binding isotherms and characterization of isolated LDL from 12 healthy controls and 12 young myocardial infarct survivors. The amount of LDL insolubilized in serum from solutions of CSPG was found to be a function of the product Bt (total binding) x the amount of serum LDL-cholesterol. Furthermore, the Bt values for the isolated LDL from controls and patients could be predicted with more than 70% certainty by using a multiple regression model which included the cholesterol/protein ratio, protein/triglyceride ratio, isoelectric point and the affinity coefficient of the lipoprotein for CSPG. The results indicate that LDL-CSPG measurements in serum are dependent upon both LDL concentration and structural properties which are related to its tendency to form complexes with arterial CSPG.
Adult↗