Biomedical subjects
L Moore
Publications and source records attributed to L Moore.
The effects of rocking, diet modifications, and antiflatulent medication on postcesarean section gas pain.
Explore the source record for details and available documents.
Radiopharmaceuticals and lactation.
Explore the source record for details and available documents.
Impact of halogenated compounds on calcium homeostasis in hepatocytes.
Halocarbons (CCl4, 1,1-dichlorethylene) cause a wide spectrum of effects and injury in hepatocytes. One early effect of these compounds is the inhibition and destruction of the endoplasmic reticulum (ER) calcium pump. Subsequent to inhibition of this pump, the ER calcium pool is depleted and cytosolic levels of calcium are increased for a prolonged period of time. This effect of halocarbons has been characterized and is similar in vivo and in vitro. The importance of this redistribution of cell calcium in expression of halocarbon injury of hepatocytes has not been fully resolved. Several degradative enzymes (phospholipases, proteases) have been implicated as calcium-dependent mediators in toxicity. Our preliminary studies of the effect of calcium redistribution suggest that activation of a calcium-sensitive endonuclease in liver does not play a central role in initiating the lethal effect of halocarbons on hepatocytes.
Sudden and unexpected death--a late effect of occult intraesophageal foreign body.
Acute upper airway obstruction in a 4-month-old male infant who presented as sudden infant death syndrome is described. At autopsy external tracheal compression and tracheobronchitis with plugging of the trachea and bronchi by an abundant mucopurulent exudate were found. The source of the inflammation was the adjacent esophagus where previous impaction of a coin had caused pressure necrosis with mucosal erosion and transmural granulation tissue formation. This case is reported to demonstrate that foreign bodies that remain in the esophagus, having by-passed the larynx, may still result in upper airway obstruction and death in early infancy by this unusual mechanism.
Disappearance of labelled IGF-2 from plasma of the ovine fetus in late gestation.
The role of IGF-2 in the fetus and its possible influence on fetal growth remains speculative. We investigated the size distribution of unsaturated binding sites for labelled oIGF-2 in ovine fetal plasma. In addition, the disappearance of each form of protein bound IGF-2 in the late gestation ovine fetus (125-135 days, n = 5) was estimated. One minute after injection into the fetal femoral vein, 125IoIGF- circulated in the fetal femoral artery bound primarily to a 50 kDa binding protein. Only a small amount of binding to a 150 kDa binding protein was seen with little to no free IGF-2 present. IGF-2 also circulated in association with a large molecular weight complex (ca. 250 kDa) presumed to be circulating receptor bound IGF-2. The half life of the 250 kDa form of IGF-2 was 385.9 +/- 65.4 min, for the 150 kDa form 308.0 +/- 65.0 min, for the 50 kDa form was 35.5 + 2.6 min and for the free form of IGF-2 was 1.6 +/- 0.6 min. There was no apparent movement of intact IGF-2 out of the fetal circulation into any of the fetal fluids or into the maternal circulation. Similarly there was no consistent placental uptake of IGF-2 from the fetal circulation.
Does rubeola (measles) vaccination in a lactating woman present a risk for the breastfeeding infant?
Explore the source record for details and available documents.
Validation of a role-play measure of children's social skills.
A videotape-administered role-play test of children's social skills was developed and its psychometric properties tested. Performance criteria for the test were derived from popular children's ratings of the effectiveness of different role-play responses. The test was administered to 157 fourth- and fifth-grade boys and girls who had been classified as popular, average, neglected, or rejected, on the basis of sociometric testing. The test evidenced good interrater, test-retest, and internal consistency reliabilities. Children's role-play performance correlated significantly with teacher ratings of social competence and with peer-liking ratings. Neglected children performed more poorly on the role-play test than popular children. When differences in intelligence among social status groups were statistically controlled, social status groups did not differ on the role-play test. Results of the discriminant analyses support the conclusion that teacher ratings are better than role-play tests for identifying rejected children, whereas role-play tests and measures of intelligence appear more accurate than teacher ratings for identifying neglected children.
Halocarbon hepatotoxicity is not initiated by Ca2+-stimulated endonuclease activation.
Previous studies from this laboratory have demonstrated that cytosolic Ca2+ rapidly rises to supraphysiologic levels in liver cells exposed to the hepatotoxins carbon tetrachloride (CCl4) and 1,1-dichloroethylene (DCE) in vivo and in vitro. The present study examines whether this increase in intracellular Ca2+ activates endonucleases that could initiate or contribute to the ensuing hepatotoxic events. Initial experiments demonstrated that there was no generalized breakdown of hepatic DNA in intact rats exposed to CCl4 and DCE, as assessed by the appearance of nucleosomal fragments in liver nuclear DNA separated on agarose gels. Nor was generalized fragmentation observed in DNA isolated from primary hepatocyte cultures exposed to halocarbons, except at very late times following loss of plasma membrane integrity. Endonuclease activation was further examined at a more sensitive level by specifically monitoring hypersensitive sites (HSS) in serum albumin gene. Actively transcribed genes, such as albumin in liver tissue, are extremely sensitive to attack by exogenous nucleolytic enzymes at discrete sites. We speculated that subtle halocarbon-induced endonuclease activation would first become evident at these sites. To locate HSS, DNA was digested with restriction enzymes Eco R1 or Hind III, electrophoresed on agarose gels, blotted onto nitrocellulose, and hybridized to a 32P-labeled 1400 bp rat albumin genomic clone. No cleavage at hypersensitive sites was detected in DNA isolated from rat liver or hepatocyte DNA at early times when elevations of Ca2+ were developing. Thus, these data indicate that endonuclease activation by intracellular Ca2+ and resultant nucleolytic destruction of DNA is not an early event in the hepatotoxicity produced by halocarbons.
A der(11)t(8;11) in two medulloblastomas. A possible nonrandom cytogenetic abnormality.
Cytogenetic analysis of tumor tissue from two patients with medulloblastoma is reported. Both showed the presence of an i(17q) and a der(11)t(8;11)(q11;p11). It is suggested that the t(8;11) may be a translocation associated with medulloblastoma.
Chronic travelers' diarrhea in a normal host due to Isospora belli.
Explore the source record for details and available documents.
Recreational drug use by the breastfeeding woman. Part 1: Illicit drugs.
Explore the source record for details and available documents.
Seizures after primary intracerebral hemorrhage.
We followed 123 patients with primary intracerebral hemorrhage (ICH), defined as bleeding without known precipitating cause except hypertension, for an average of 4.6 years or until death in order to determine the incidence, prevalence, and type of epileptic seizures. Twenty-five percent had seizures. In one-half of these, the seizures began within 24 hours of the hemorrhage. Survival table analysis predicted a potential cumulative seizure incidence of 50%, had all patients survived 5 years. Seizure incidence was high with bleeding into lobar cortical structures (54%), low with basal ganglionic hemorrhages (19%), and zero with thalamic hemorrhages. Within the basal ganglia, caudate involvement predicted seizures; within the cortex, temporal or parietal involvement predicted seizures. Although seizure incidence was high, prevalence of chronic epilepsy was much lower: 13% in 30-day to 2-year survivors and 6.5% in 2- to 5-year survivors. Seizure incidence is higher than previously reported after ICH because small lobar hemorrhages are the most epileptogenic and are now easily recognized with computed tomography.
Characterization of insulin-like growth factor binding proteins in ovine tissue fluids.
Competitive tracer binding studies using radioiodinated insulin-like growth factor-I and -II (125I-labelled IGF-I and 125I-labelled IGF-II) together with size exclusion chromatography and IGF-I affinity chromatography have been used to characterize IGF binding protein activity in ovine tissue fluids. Binding proteins of greater than 200, 150 and 40-50 kDa were revealed in these studies and shown to be widely distributed in body fluids. Thus, the greater than 200 kDa binding protein, which is IGF-II specific, is present in plasma from mature sheep, colostrum and follicular fluid as well as fetal sheep plasma. This may be the ovine equivalent of the soluble type-2 IGF receptor recently identified in rat serum. The presence of a 150 kDa binding protein, of mixed specificity for IGF-I and IGF-II, in fetal and mature sheep plasma was confirmed in these studies. This protein, previously believed to be restricted to vascular fluids, was also identified in mammary lymph, follicular fluid and as a minor component in vitreous humor. Binding proteins of 40-50 kDa were revealed in every fluid tested and multiple variants with distinct specificities were also suggested. This was investigated by IGF-I affinity chromatography using mature sheep plasma. Following passage through the affinity adsorbent, binding of 125I-labelled IGF-I to proteins in the 40-50 kDa region was abolished but when 125I-labelled IGF-II was used as tracer, a binding protein of 40-50 kDa was still observed. Thus sheep plasma contains at least two 40-50 kDa binding proteins. The competitive tracer binding studies indicated that one such protein demonstrates mixed specificity for IGF-I and -II while the other strongly favours IGF-II.
Evaluation of the calcium mobilizing action of acetaminophen and bromobenzene in rat hepatocyte cultures.
Acetaminophen (APAP) and bromobenzene (BrB) are reported to selectively inhibit plasma membrane (PM) but not endoplasmic reticulum (ER) Ca2+ transport in rat liver (1). The ability of these hepatotoxicants to increase cytoplasmic Ca2+ levels as a result of disrupted Ca2+ pumping was determined in cultured rat hepatocytes by monitoring the activity of glycogen phosphorylase alpha, a Ca2+ -sensitive (via phosphorylase kinase) enzyme. Following exposure to 2.5 to 10 mM APAP for five minutes, dose-dependent increases in phosphorylase alpha activity were observed (58 to 190 U/g protein). Endoplasmic reticulum Ca2+ pump activity was not inhibited after any dose of APAP (56 nmol Ca2+ per milligram protein per 30 minutes). Phosphorylase alpha activity remained elevated for 60 minutes after exposure to APAP (124 microliters/g protein). Following exposure to 0.5 to 2 mM BrB for five minutes, phosphorylase alpha activity also increased (58 to 229 U/g protein) in a dose-related manner. Endoplasmic reticulum Ca2+ pump activity was inhibited after BrB exposure (from 58 to 16 nmol Ca2+ per milligram protein per 30 minutes). Phosphorylase alpha activity remained elevated for 60 minutes after exposure to BrB (147 U/g protein). Evidence of elevated cytoplasmic Ca2+ is consistent with the inhibition of Ca2+ -extruding/sequestering mechanisms at hepatocyte PM and/or ER. Prolonged elevation of cytosolic Ca2+ levels could overstimulate Ca2+ -sensitive processes within liver cells and thus initiate or contribute to hepatotoxic injury.
Stimulation of the renal endoplasmic reticulum calcium pump: a possible biomarker for platinate toxicity.
Antitumor platinum compounds such as cisplatin are frequently nephrotoxic. The mechanism of nephrotoxicity has not been determined. It has been proposed that some toxicants may act by interfering with the mechanisms that control cellular Ca2+ homeostasis. An important factor in the regulation of cytosolic Ca2+ is the endoplasmic reticulum (ER) calcium pump. The activity of this pump was determined by measuring ATP-dependent microsomal sequestration of 45Ca. Administration of nephrotoxic doses of platinum compounds to rats was associated with an increase in renal ER calcium pump activity. This was the earliest response observed after cisplatin treatment (it occurred within 4 hr) and preceded increases in blood urea nitrogen and serum creatinine by at least 1 day. The dose-response curve for the increase in renal ER calcium pump activity was similar to the increase in the number and size of smooth ER aggregates observed in the S3 segment of the proximal tubule 24 hr following cisplatin administration. Only minor morphological changes were observed at this time. There was a significant increase in calcium content of kidneys of rats 24 hr after treatment with a dose of cisplatin that caused a maximal increase in ER calcium pump activity. This indicates that a disruption of normal calcium homeostasis may occur before histological evidence of nephrotoxicity. Platinates that were not toxic to the kidney did not elevate renal ER calcium pump activity. It is suggested that the activity of the ER calcium pump may be a useful biomarker for cellular toxicity and may be a factor in the mechanism of toxicity.
Biochemical evaluation of rat hepatocyte primary cultures as a model for carbon tetrachloride hepatotoxicity: comparative studies in vivo and in vitro.
In order to evaluate how well the development of CCl4 hepatotoxicity in vivo can be modeled in primary cultures of rat hepatocytes, biochemical alterations were determined in liver samples from rats given CCl4 and in liver cells cultured for 18 hr then exposed to CCl4. Soluble thiol levels matched closely between tissue and hepatocytes (11 vs 12 micrograms-SH/mg protein) prior to exposure. Comparable concentrations of CCl4 were measured in blood (0.30 mM at 30 min) and in culture medium (0.49 mM at 5 min). Simultaneous inhibition of the endoplasmic reticulum calcium pump and stimulation of phosphorylase a activity occurred at early times in vivo (30 min) and in vitro (5 min). Glucose-6-phosphatase was inhibited next in liver (120 min) and in cells (20 min). 5'-Nucleotidase was not affected at any time points examined in either system. Leakage of glutamic-pyruvic transaminase and depletion of glycogen were maximal at later times in vivo (greater than or equal to 8 hr) and in cells (30 min). Total calcium content was increased severalfold in liver tissue (24 hr), but was not elevated in hepatocytes. This lack of calcium accumulation in cells appeared to result from impaired mitochondrial calcium uptake. Thus CCl4-induced biochemical changes followed nearly the same continuum in both models, although the progression was much more rapid in vitro than in vivo.
Pharmacokinetics and bioavailability of hydromorphone: effect of various routes of administration.
The pharmacokinetics and bioavailability of hydromorphone following various routes of administration, i.e., intravenous, oral, intranasal, and transdermal, were investigated in rabbits. Hydromorphone plasma concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC). Comparison of area under the concentration versus time curve (AUC) between intravenous and oral administrations showed a low bioavailability of hydromorphone after oral administration. The nasal absorption of hydromorphone was studied by the in situ nasal recirculation technique, and the results showed that hydromorphone is well absorbed from the nasal mucosa. The transdermal permeation of hydromorphone was also evaluated for 24 hr and a steady-state plasma concentration (0.135 micrograms/ml) was achieved during the 6- to 24-hr periods following the application of a transdermal patch on the inner pinna of the rabbit's ear.