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Biomedical subjects

G Lopez

Publications and source records attributed to G Lopez.

At least 55 records · Page 3Linked to original sources

Idiopathic epilepsy with generalized tonic clonic seizures in Antioquia, Colombia: is the joint Amerindian and Negroid racial admixture the cause of its high prevalence?

Most Colombian populations stem from the admixture of Caucasians, Amerindians and Negroids. In the world, these two latter ethnical groups show a significantly higher prevalence of epilepsy than the former one. We tested the hypothesis that the high prevalence of idiopathic epilepsy with generalized tonic clonic seizures found in the Antioquian population (Paisas), from Colombia, is due to their possible joint Negroid and Amerindian ethnic components. We have previously demonstrated that inheritance is the principal factor for developing epilepsy in this community. Analyses of racial admixture, heterogeneity between populations, genetic distance, and phyletic relationships were performed among epileptic and non epileptic samples from the Antioquian community. Also Caucasians, Spaniards, Basques, Jews, Chileans, Negroids, Amerindians and Mongoloids were included in the analysis. Four highly polymorphic blood systems were used as genetic markers: RH, MNS, ABO and FY. They were chosen because of their high discriminant power in these ethnic groups. In the population affected with idiopathic epilepsy, the estimated Negroid and Amerindian rates of admixture were low (3% and 14%, respectively). Although, these degrees of admixture can be explained due to common ancestral origins, the estimated proportion of Amerindian admixture in the epileptic affected population, was significantly higher than the estimated for the Non affected Antioquian population. The latter finding is consistent with the analysis of heterogeneity between populations that discriminated epileptic population from non epileptic Antioquian population (p < 0.05). Epileptic and non epileptic Paisas clustered in topology with Caucasians, very close to Spaniards and Basques and highly distant from Negroids and Amerindians. Thus, far, the origin of the high prevalence of idiopathic epilepsy in the Antioquian (Paisa) population cannot be explained by the hypothetical joint Negroid and Amerindian ethnical admixture, but using additional genetic markers and other methods of racial estimation of admixture it is necessary to corroborate if the Amerindian admixture component is significantly higher in the epileptic population than in the non epileptic Paisa population.

Black People↗

Determinants of plasma pepsinogen levels in a population at high risk for stomach cancer in Venezuela.

Determinants of plasma pepsinogens (PG) levels were studied in 1365 participants in a chemoprevention trial for gastric pre-cancerous lesions being conducted in Venezuela. Gastric biopsies, plasma samples and information on smoking and dietary habits were obtained at baseline examination. Both PG-I and PG-II levels increased progressively with the level of Helicobacter pylori infection in gastric biopsies, resulting in no clear trend in the I/II ratio. Instead, there was a progressive decrease in the I/II ratio with increasing degrees of infiltration of polynuclear cells and monocytes, atrophy, intestinal metaplasia and the stage of pre-cancerous lesions. The mean I/II ratios for atrophic gastritis or more advanced lesions were less than 4.0. When subjects with the I/II ratio 4 or higher were used as controls, severe reduction in the I/II ratio (< 2.0) was inversely associated with tobacco consumption. This may be due to a pharmacological effect of nicotine. The severe reduction of I/II ratio was also inversely associated with fresh fruit consumption. In addition, a decreased I/II ratio was positively associated with rice/pasta and arepas (tortilla made from corn) consumption and inversely associated with plantain consumption. Possible effects of vitamins and starchy food on the development of atrophic gastritis need to be studied further.

Adult↗

Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor.

A conserved region in the hormone-dependent activation domain AF2 of nuclear receptors plays an important role in transcriptional activation. We have characterized a novel nuclear protein, RIP140, that specifically interacts in vitro with this domain of the estrogen receptor. This interaction was increased by estrogen, but not by anti-estrogens and the in vitro binding capacity of mutant receptors correlates with their ability to stimulate transcription. RIP140 also interacts with estrogen receptor in intact cells and modulates its transcriptional activity in the presence of estrogen, but not the anti-estrogen 4-hydroxytamoxifen. In view of its widespread expression in mammalian cells, RIP140 may interact with other members of the superfamily of nuclear receptors and thereby act as a potential co-activator of hormone-regulated gene transcription.

Adaptor Proteins, Signal Transducing↗

Transcriptional activators differ in their responses to overexpression of TATA-box-binding protein.

We investigated how overexpression of human TATA-box-binding protein (TBP) affects the action of estrogen receptor (ER) and compared the response with that of other activators. When ER activates a simple promoter, consisting of a response element and either the collagenase or tk TATA box, TBP overexpression potentiates transcription. TBP potentiates only estrogen-induced and not basal transcription and does so independent of spacing between response element and TATA box. TBP overexpression also reduces autoinhibition by overexpressed ER, suggesting that one target of the autoinhibition may be TBP itself. Both AF-1 and AF-2 domains of ER are potentiated by TBP, and each domain binds TBP in vitro. Like ER, chimeric GAL4/VP16 and GAL4/Tat activators are also potentiated by TBP, as is the synergistic activation by ER and GAL4/VP16 on a complex promoter. Unlike ER, GAL4/Sp1 and GAL4/NF-I become less potent when TBP is overexpressed. Furthermore, synergy between ER and Sp1 or between ER and NF-I, whether these are supplied by transfected GAL4 fusions or by the endogenous genes, is inhibited by TBP overexpression. Thus, ER resembles VP16 in response to TBP overexpression and is different from Sp1 and NF-I, which predominate over ER in setting the response on complex promoters.

Animals↗

Response of broiler breeders to low-protein diets. 1. Adult breeder performance.

Four hundred female and 50 male commercial strain breeders were reared separately from 1 d to 18 wk of age, with all birds receiving the same diet. At 18 wk, all pullets were weighed and the extreme weights removed from the group. The remaining hens were then randomly sorted into four treatment groups each represented by four replicate groups. Treatment involved feeding different levels of CP (16, 14, 12, and 10%), supplemented with synthetic lysine and methionine in order to maintain constant lysine and TSAA levels, respectively. Diets were isoenergetic and all birds received the same quantity of feed daily. Dietary protein had no effect on egg production (P > .05). However, breeders fed 10% CP were lighter (P < .01) in weight than birds fed 16% CP. Eggs from birds fed 10 and 12% CP were consistently smaller (P < .01), and this resulted in reduced chick weight at hatching. Low-protein diets also resulted in less nitrogen excretion. These data suggest that it is possible to reduce the CP intake of broiler breeders while maintaining intake of critical amino acids without affecting performance.

Amino Acids↗

Response of broiler breeders to low-protein diets. 2. Offspring performance.

Broiler breeders were allocated at random to one of four experimental diets containing various levels of CP (16, 14, 12, or 10%), at constant methionine+cystine and lysine levels of .59 and .82%, respectively. Diets were isoenergetic and all birds received the same quantity of feed daily to 64 wk of age. Eggs from birds fed 10 and 12% CP were consistently smaller (P < .01) and in two trials involving breeders at 30 and 52 wk of age this resulted in reduced chick weight at hatching, although no lasting effect was observed on weight of offspring at 48 d. Better feed efficiency (P < .05) was observed from broilers hatched from hens fed lower CP diets. These data suggest that it is possible to reduce the CP intake of broiler breeders while maintaining intake of critical amino acids without adversely affecting offspring performance.

Animals↗

Intraurethral capsaicin produces reflex activation of the striated urethral sphincter in urethane-anesthetized male rats.

The effect of intraurethral application of capsaicin on the urethral motility of urethane anesthetized rats has been investigated. The urinary bladder and the urethra were surgically disconnected, and both organs were cannulated to record variations in intraluminal pressure (cystourethrogram). Urinary bladder reflex contractions in response to intravesical infusion of saline were paralleled by activation of the external striated urethral sphincter, resulting in intraluminal pressure high frequency oscillations (IPHFO) which were recorded at the urethral level. Intraurethral capsaicin (0.2 microgram./30 microliters.), produced an immediate enhancement of the IPHFO, the amplitude of which (70 +/- 9 mm.Hg) was significantly (p < 0.01) higher as compared with that recorded before drug administration (15 +/- 3 mm.Hg). The potentiation was followed (11 of 15 rats) by a period (5 to 12 minutes) characterized by a continuous low-amplitude urethral phasic activity. Throughout this period urinary bladder motility was inhibited. A second administration of capsaicin in the same animal was ineffective, and the response was absent in rats desensitized to capsaicin (50 mg./kg., subcutaneously, 4 days before), after application of tetrodotoxin (10 micrograms.) on the pudendal nerves, or after acute (3 hours before) sectioning, as well as in rats pretreated with d-tubocurarine (d-Tc, 100 micrograms./kg. intravenously). Intraurethral injection of capsaicin (0.2 microgram./30 microliters.), performed when the urinary bladder was empty, triggered IPHFO (12 +/- 3 mm.Hg) in 5 of 6 rats. This response was unaffected by hexamethonium (20 mg./kg., intravenously) or after removal (6 hours before) of the major pelvic ganglia, while it was absent after destruction of the lumbosacral spinal cord (3 to 6 hours before), in rats acutely spinalized (T13-L1), or after sectioning of the pudendal nerves. In rats receiving intrathecal (L5-S1) capsaicin (60 micrograms., 24 hours before), the capsaicin-induced IPHFO activation was lacking. Electrical field stimulation (EFS, 0.1 Hz, 30 microseconds, 20 to 30 v) of the rat isolated external urethral sphincter (EUS), elicited d-tubocurarine and tetrodotoxin-sensitive twitch contractions, the amplitude of which was unaffected by capsaicin (1 microM.). Altogether these results suggest a physiological interaction between capsaicin-sensitive primary afferents innervating the urethra and the somatic efferent innervation to the urethral rabdosphincter. Present findings suggest the existence of a chemonociceptive urethro-urethral neural loop which, via pudendal nerves, leads to a supraspinally-mediated activation of the external urethral sphincter.

Afferent Pathways↗

Positive and negative modulation of Jun action by thyroid hormone receptor at a unique AP1 site.

We have characterized the putative AP1 site in the backbone of pUC plasmids and found unique regulatory effects. The site, which mapped to a 19-bp region around nucleotide 37, conferred transcriptional activation by Jun or Jun/Fos that was boosted up to fivefold by unliganded thyroid hormone receptor (TR). Thyroid hormone changed potentiation of the Jun response by TR into repression. Although the plasmid sequence is a near-perfect consensus AP1 site, the perfect consensus AP1 site from the human collagenase promoter did not show the same effects. Deletion of the ligand binding domain of the TR eliminated the ability of the receptor to boost Jun activity, and deletion, mutation, or changes in specificity of the DNA binding domain eliminated both its ability to potentiate Jun activity and repress with hormone. In vitro Jun/Fos complexes bound the operative plasmid fragment, and the presence of TR interfered very little with Jun/Fos binding activity. Protein interaction studies in the absence of DNA showed that TR bound Jun protein in solution either in the presence or in the absence of hormone. These observations suggest a mechanism for synergy and repression by TR through modulation of Jun activity: positive when TR is unliganded, and negative when hormone is bound. They also suggest that the presence of the plasmid element can confound studies of the regulation of linked promoters.

Animals↗

Generation of cytotoxic immune responses against a rat glioma by in vivo priming and secondary in vitro stimulation with tumor cells.

Cytotoxic T lymphocyte (CTL) responses to most antigens are generated by in vivo priming and secondary stimulation with antigen in vitro. The present studies were designed to determine whether that strategy could be used to stimulate development of CTL against brain tumors. Rats were primed with one of two tumors, RT2, an astrocytoma, or 9L, a gliosarcoma, and Corynebacterium parvum. Spleen cells from primed rats were stimulated with tumor cells and interleukin-2 in vitro to generate CTL. CTL generated against RT2 killed RT2 and 9L, but not allogeneic or histopathologically unrelated tumor cells, suggesting that the killing was brain tumor-specific and major histocompatibility complex gene product-restricted. Similar results were obtained with rats primed and secondarily stimulated with 9L. Specific cytotoxic cells only developed when syngeneic brain tumor cells were used for both priming and secondary stimulation. The cytotoxic cell populations were composed of OX-19+ T cells with a mixed CD4/CD8 phenotype. Controls consisting of spleen cells from unprimed or primed rats tested before culture exhibited low levels of cytotoxicity against brain tumor targets. Culturing unprimed or primed cells with interleukin-2 alone stimulated cell proliferation, but the cells that grew out exhibited only low levels of cytotoxicity for brain tumor cells. Cell populations exhibited consistent cytotoxicity against natural killer cell targets. None of the cell populations killed lymphokine-activated killer cell targets. The results demonstrated that brain tumor-specific CTL could be produced by priming in vivo followed by secondary stimulation with brain tumor cells in vitro. The results further demonstrated that RT2 and 9L share antigens that both induce and serve as target structures for specific cytotoxic cells.

Adjuvants, Immunologic↗

Environmentally-induced methemoglobinemia in an infant.

Acquired methemoglobinemia results from the exposure to various chemicals and drugs able to oxidize hemoglobin at a rate exceeding the normal enzymatic capacity for hemoglobin reduction. Levels of methemoglobin exceeding 60-70% may be associated with coma and death. We describe a case of complete, uneventful recovery involving a 10 week-old infant who presented to the Emergency Department with profound sudden onset of cyanosis, irritability, metabolic acidosis, and a lethal methemoglobin level of 71.4%. Intravenous administration of 12 mg methylene blue resulted in immediate resolution of the cyanosis and reduction of measured methemoglobin to 1.3%. The carboxyhemoglobin was negative. Sodium bicarbonate successfully corrected the acidosis. RBC reductase measurement was within normal limits, ruling out congenital methemoglobinemia. Family history revealed a wood-burning stove which emitted pine tar fumes as the potential environmental methemoglobin-producing source. The infant's cradle was situated five feet from the stove. The infant was discharged on day three of hospitalization with a methemoglobin level of 0.2%.

Creosote↗

Simultaneous recording of vesical and urethral pressure in urethane-anesthetized rats: effect of neuromuscular blocking agents on the activity of the external urethral sphincter.

In urethane-anesthetized rats we made a disconnection of the urinary bladder from the urethra and performed a simultaneous recording of the vesical and external urethral sphincter (EUS) pressures. Throughout the collecting phase, the EUS pressure was higher than that recorded into the bladder. Gallamine (10 mg/kg i.v.) or d-tubocurarine (100 micrograms/kg i.v.), did not alter the value of intraurethral pressure. When a reflex bladder contraction occurred in response to filling (expulsion phase) the intravesical pressure exceeded the urethral pressure and at the top of the vesical contraction a series of rapid intraluminal pressure high frequency oscillations (IPHFO) were recorded at the urethral recording site, which were abolished by neuromuscular blocking agents as well as after acute sectioning of pudendal nerves. IPHFO was still present in rats in which the periurethral muscles (pelvic floor), have been precedently dissected. To get further information about the physiological consequence of the EUS functional impairment induced by neuromuscular blocking agents, we used the non-stop transvesical cystometrogram. In these conditions, blockade of the EUS did not produce passive urine dripping during the filling phase, but absence of the rhythmic striated urethral activity during the vesical expulsion phase produced a significant increase of the residual volume from 35% (control) to 75%. We present an original pharmacological method in a species whose small dimensions create technical problems for recording pressure signals from the lower urinary tract. Moreover, we have gained information on the origin of the IPHFOs and about the role of the EUS during the collecting and the expulsion phase of the voiding cycle in urethane anesthetized rats.

Animals↗

Anatomy of the gonadal veins: a reappraisal.

Variations in anatomy were found quite frequently during bilateral gonadal vein dissection and resection for pelvic varices in the past 5 years (120 cases). In about one fourth of the cases, routine gonadal phlebography was not technically feasible or did not correlate exactly with the operative findings. Some cases of male varicocele showed recurrence after surgery. These facts, in addition to the scarce information provided by anatomy textbooks, induced us to study thoroughly the gonadal veins. One hundred cadaver dissections (200 veins) were done for length, diameter, number, and location of valves and collaterals, number of trunks in each side, and mode of termination in the renal vein and vena cava. Topographic division of the veins by thirds facilitated the information. Variations from the classic anatomic description were encountered frequently. As to the number of trunks, at the middle third, where the vein is usually divided, only 60% have one trunk on the left and only 75% have one on the right side. The rest are multiple; as many as four and six trunks in the lower third were found. The knowledge of these anatomic variations, not clearly described before, is of great importance to both surgeons and invasive radiologists and conducive to successful results.

Adolescent↗

Accidental childhood death from diphenhydramine overdosage.

A 15-month-old boy presented to an emergency department with tonic clonic jerking of all extremities and dancing eye movements. A history of instant coffee ingestion was obtained at that time. However, a routine blood analysis and toxicology screen showed a diphenhydramine level of 1.0 mg% (lethal, 0.5 mg%). Generalized tonic clonic seizures continued despite conventional therapy. A continuous thiopental infusion was used to control his seizure activity. This child never regained consciousness and was pronounced dead 7 days postingestion.

Diphenhydramine↗

Monoclonal antibodies to the VP6 of porcine subgroup I rotaviruses reactive with subgroup I and non-subgroup I non-subgroup II strains.

A panel of 10 monoclonal antibodies produced after immunization with two porcine subgroup I rotavirus strains (OSU and A46), and directed against the major inner capsid protein (VP6), fell into six patterns of reactivity when tested against a collection of human and animal group A rotavirus strains. Monoclonal antibodies of pattern I recognized all rotavirus strains. Antibodies of patterns 2 and 3 recognized all subgroup II strains and some, but not all, subgroup I strains. Pattern 4 antibodies identified all subgroup I strains and two strains (H2, equine; CC117, porcine) not reactive with reference subgroup monoclonal antibodies (strains non-I non-II). Pattern 5 antibody exhibited the same reactivity as pattern 4 except for not recognizing the non-I non-II equine strain. Pattern 6 antibodies reacted exclusively with subgroup I and non-I non-II rotaviruses of porcine origin. By competitive binding assays, monoclonal antibodies of patterns 4, 5 and 6 appeared to recognize a single antigenic site, which included at least three overlapping epitopes. In immunoblots all monoclonal antibodies, except one, recognized only the trimeric, but not the monomeric form of VP6.

Animals↗

Incidence of antibodies blocking thyrotropin effect in vitro in patients with euthyroid or hypothyroid autoimmune thyroiditis.

Autoantibodies blocking the TSH-dependent production of cAMP in thyroid cells (TSH-BAb) have been described in atrophic thyroiditis (AT; idiopathic myxedema) and in neonates with transient hypothyroidism, but their incidence in autoimmune thyroiditis in relation to thyroid status remains to be completely established. To this purpose TSH-BAb were evaluated in a group of 140 consecutive patients with autoimmune thyroiditis, which included 26 cases of AT and 114 subjects with goitrous Hashimoto's thyroiditis (HT); among the goitrous group 27 were euthyroid (HT-E), 32 had subclinical hypothyroidism (HT-SH), and 55 had clinical hypothyroidism (HT-H). TSH-BAb were measured in immunoglobulin G prepared by DEAE-Sephadex A-50 by determining their ability to inhibit TSH-dependent cAMP production in a differentiated strain of cultured rat thyroid cells (FRTL-5). Using this sensitive and reproducible method, TSH-BAb were detected in 12 of 26 (46%) patients with AT, in 1 of 27 (3.7%) subjects with HT-E, in 3 of 32 (9.4%) with HT-SH, and in 20 of 55 (36%) with HT-H. The prevalence of TSH-BAb was higher in AT vs. HT-H (P less than 0.001), HT-SH (P less than 0.001), or HT-E (P less than 0.001), and in HT-H vs. HT-SH (P less than 0.001) or HT-E (P less than 0.001). Mean TSH-BAb levels in AT were higher than those in HT-H (P less than 0.005) and HT-SH (P less than 0.025); the difference was not significant between HT-H and HT-SH. An inverse correlation was found between TSH-BAb levels and estimated goiter weight (P less than 0.005). The results of the present study indicate that 1) in autoimmune thyroiditis TSH-BAb are detectable almost exclusively in hypothyroid patients, their prevalence being higher in overt hypothyroidism than in subclinical thyroid failure; 2) the prevalence of TSH-BAb and their mean levels are higher in hypothyroid patients with AT than in those with HT; and 3) therefore, the presence of circulating TSH-BAb appears to be related to the development of hypothyroidism and thyroid atrophy.

Adult↗