PubMed HealthSearch

Biomedical subjects

H Moskowitz

Publications and source records attributed to H Moskowitz.

17 recordsLinked to original sources

Localization of receptor sites for insect-selective toxins on sodium channels by site-directed antibodies.

Site-directed antibodies corresponding to conserved putative extracellular segments of sodium channels, coupled with binding studies of radiolabeled insect-selective scorpion neurotoxins, were employed to clarify the relationship between the toxins' receptor sites and the insect sodium channel. (1) The depressant insect toxin LqhIT2 was shown to possess two noninteracting binding sites in locust neuronal membranes: a high-affinity (KD1 = 0.9 +/- 0.6 nM) and low-capacity (Bmax1 = 0.1 +/- 0.07 pmol/mg) binding site as well as a low-affinity (KD2 = 185 +/- 13 nM) and high-capacity (Bmax2 = 10.0 +/- 0.6 pmol/mg) binding site. (2) The high-affinity site serves as a target for binding competition by the excitatory insect toxin AaIT. (3) The binding of LqhIT2 was significantly inhibited in a dose-dependent manner by each of four site-directed antibodies. The binding inhibition resulted from reduction in the number of binding sites. (4) The antibody-mediated inhibition of [125I]AaIT binding differs from that of LqhIT2: three out of the four antibodies which inhibited LqhIT2 binding only partially affected AaIT binding. Two antibodies, one corresponding to extracellular and one to intracellular segments of the channel, did not affect the binding of either toxin. These data suggest that the receptors to the depressant and excitatory insect toxins (a) comprise an integral part of the insect sodium channel, (b) are formed by segments of external loops in domains I, III, and IV of the sodium channel, and (c) are localized in close proximity but are not identical in spite of the competitive interaction between these toxins.

Animals

Sedating effects of ethanol and time of drinking.

Ethanol (0.5 g/kg) was administered to 12 healthy, normal-sleeping men, aged 21 to 45, at two different times of the day (0900 and 1700 hr). The Multiple Sleep Latency Test (MSLT) was conducted at 1000, 1200, 1400, and 1600 hr in the day drinking condition and at 1800, 2000, 2200, and 2400 hr in the evening drinking condition. On placebo, sleepiness was greater in the daytime testing hours than in the evening, replicating findings on the circadian rhythm of sleepiness/alertness. There was a time of drinking (day versus evening) by ethanol interaction. An ethanol effect on sleep latency was found in the daytime hours, when alertness was relatively low. Ethanol failed to have a significant effect on sleep latency during the evening hours when alertness levels were increasing. Performance on a divided attention task, administered 1 hr postconsumption, was impaired by ethanol consumption, but did not vary as a function of time of drinking (day versus evening). However, at 5 hr postconsumption, mean reaction time on the first 20 min of a 40-min auditory vigilance task was slowed by ethanol to a greater extent after day drinking then after evening drinking.

Adult

Solubilization and characterization of the insect neuronal sodium channel.

Locust neuronal sodium channels were solubilized by 1% cholate and 0.2% Triton X-100, and their functionality was monitored by [3H]saxitoxin (STX) binding assays. About 40% of STX binding activity was recovered in the solubilized fraction without affecting affinity (Kd = 0.5 nM) and the time and temperature dependent STX binding activity was significantly stabilized in the presence of 20 nM STX. Partial purification by an anion exchange resin yielded a 20% recovery and a 3.5 times increase in the specific STX binding activity. Identification of the locust solubilized sodium channels by immunoprecipitation and radiophosphorylation revealed a Mr of 245,000 on SDS-PAGE. The present solubilized preparation will enable the study of the unique pharmacology of insect sodium channels.

Animals

Effect of alcohol and marijuana on eye movements.

The effects of alcohol and marijuana (tetrahydrocannabinol-THC) on saccades, smooth pursuit, and optokinetic nystagmus were quantitatively evaluated in 24 normal subjects using electro-oculographic recordings. Each subject was given an initial trial run and then tested three times (at weekly intervals) with either 0.0microgram THC or 100 microgram THC/kg bodyweight while at three different blood alcohol concentrations (0.0, 0.05 and 0.1%). A 2X3 factorial design was used. Saccades and smooth pursuit were induced by a dot of light moving in steps and ramps on a modified television set. Optokinetic nystagmus was induced by a cloth drum completely surrounding the subject and moving at a constant velocity of 30 degrees/s. Alcohol (0.05 and 0.1%) alone produced significant (p less than 0.05) impairment of saccade maximum velocity and reaction time, smooth pursuit velocity, and optokinetic slow-component velocity. The addition of THC caused performance to further deteriorate at each blood alcohol level but, in all but one instance, the added effect was not statistically significant ( greater than 0.05). At the THC and alcohol concentrations used in this study, the eye movement effects of alcohol over-shadowed those of marijuana.

Adult

Prognostic significance of portal pressure in patients with bleeding esophageal varices.

Portal pressure was determined in 76 patients during acute bleeding varices, and the degree of portal hypertension was related to the cessation or noncessation of hemorrhage with nonoperative management. A direct relationship between the severity of hemorrhage and the degree of portal hypertension was established. It is suggested that portal pressure be determined as soon as feasible when bleeding varices are suspected and that other causes of hemorrhage be carefully excluded. The obtained data are of great prognostic significance and might be helpful in planning the course of therapy in these individuals.

Adult

Decrease of iconic memory after alcohol.

Alcohol did not alter the rate of information loss from iconic memory. However, there was a dose-related decrease in the total amount of information reported which was independent of the rate of information loss.

Adult

Issues in drug-related performance impairment.

Performance impairment associated with alcohol, drugs, and medical disorders is of increasing concern to clinicians. Understanding and assessing performance impairment associated with a particular drug or condition is complex and requires careful, critical evaluation of the literature. Awareness of the issues involved enhances the ability of the clinician to assess risks for a given patient and of a given medical therapy. Important study variables are described that should be considered when evaluating the literature pertaining to performance impairment. The clinical relevance of the results of performance studies is also discussed.

Drug-Related Side Effects and Adverse Reactions