The Dok-3/Grb2 adaptor module promotes inducible association of the lipid phosphatase SHIP with the BCR in a coreceptor-independent manner.

The SH2 domain-containing inositol 5'-phosphatase (SHIP) plays a key role in preventing autoimmune phenomena by limiting antigen-mediated B cell activation. SHIP function is thought to require the dual engagement of the BCR and negative regulatory coreceptors as only the latter appear capable of recruiting SHIP from the cytosol to the plasma membrane by the virtue of phosphorylated immunoreceptor tyrosine-based inhibitory motifs. Here, we demonstrate a coreceptor-independent membrane recruitment and function of SHIP in B cells.

The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters.

Recruitment of the growth factor receptor-bound protein 2 (Grb2) by the plasma membrane-associated adapter protein downstream of kinase 3 (Dok-3) attenuates signals transduced by the B cell antigen receptor (BCR). Here we describe molecular details of Dok-3/Grb2 signal integration and function, showing that the Lyn-dependent activation of the BCR transducer kinase Syk is attenuated by Dok-3/Grb2 in a site-specific manner. This process is associated with the SH3 domain-dependent translocation of Dok-3/Grb2 complexes into BCR microsignalosomes and augmented phosphorylation of the inhibitory Lyn target SH2 domain-containing inositol 5' phosphatase.

Acute marihuana (THC) exposure produces a "transient" topographic quantitative EEG profile identical to the "persistent" profile seen in chronic heavy users.

In two published pilot studies and a controlled replication using screened normals, chronic marihuana (THC) use was associated with a unique topographic quantitative EEG profile, consisting of significant elevations of Absolute and Relative Power and Coherence of alpha activity over the bilateral frontal cortex as well as a significant decrease in alpha frequency. This report attempts to establish the causal influence of THC in the above findings by the transient production of this exact quantitative EEG profile in subjects who did not display it at the beginning. Using paced smoking of marihuana with high and low dose THC content and placebo marihuana in a counterbalanced design under double blind conditions, all four of the topographic features of chronic THC exposure were produced as transient effects by THC but not by placebo.

Paradoxical embolism to the left main coronary artery: visualization by transesophageal echocardiography.

A case of myocardial infarction is described with transesophageal echocardiography visualization of left main coronary artery thrombus arising from paradoxical embolism of mobile venous thrombus by patent foramen ovale.

Temporal indication of marijuana use can be estimated from plasma and urine concentrations of delta9-tetrahydrocannabinol, 11-hydroxy-delta9-tetrahydrocannabinol, and 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid.

Current technology establishes marijuana use based upon detection of the pharmacologically inactive cannabinoid metabolite (11-nor-delta9-carboxy-tetrahydrocannabinol-9-carboxylic acid, THC-COOH) in urine. No accurate prediction of time of use is possible because THC-COOH has a half-life of 6 days. To determine if a temporal relationship between marijuana use and metabolite excretion patterns could be established, eight healthy user-volunteers (18-35 years old) smoked marijuana cigarettes containing 0% (placebo), 1.

Topographic quantitative EEG sequelae of chronic marihuana use: a replication using medically and psychiatrically screened normal subjects.

In two previous studies it was reported that chronic marihuana (THC) use was associated with unique quantitative EEG features which were present in the non-intoxicated state. THC users, as contrasted with controls, had significant elevations of Absolute Power, Relative Power, and Coherence of alpha activity over the bilateral frontal cortex. Furthermore, a quantitative EEG discriminant function analyses permitted a 95% correct user versus non-user classification.

Cannabinoids in humans. II. The influence of three methods of hydrolysis on the concentration of THC and two metabolites in urine.

Glucuronide conjugates of cannabinoids were previously identified in humans. For gas chromatographic-mass spectrometric (GC-MS) analysis of the unconjugated compounds in human urine, it is necessary to cleave the glucuronide moiety. Base hydrolysis and two forms of enzymatic hydrolysis were compared in this study to examine any quantitative differences between the hydrolysis methods.

Cannabinoids in humans. I. Analysis of delta 9-tetrahydrocannabinol and six metabolites in plasma and urine using GC-MS.

This report describes a method for the quantitative analysis of delta 9-tetrahydrocannabinol and six of its metabolites, 8 alpha-hydroxy-delta 9-tetrahydrocannabinol, 8 beta-hydroxy-delta 9-tetrahydrocannabinol, 11-hydroxy-delta 9-tetrahydrocannabinol, 8 alpha,11-dihydroxy-delta 9-tetrahydrocannabinol, 8 beta,11-dihydroxy-delta 9-tetrahydrocannabinol, and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol. In addition, the method was designed to detect cannabidiol and cannabinol, two naturally occurring cannabinoids. Plasma and urine samples were hydrolyzed with bacterial (Escherichia coli) beta-glucuronidase and extracted with hexane-ethyl acetate (7:1).

Solid-phase extraction and GC/MS quantitation of cocaine, ecgonine methyl ester, benzoylecgonine, and cocaethylene from meconium, whole blood, and plasma.

A selective solid-phase extraction technique has been applied to the analysis of cocaine and selected cocaine metabolites in meconium, whole blood, and plasma. This technique uses a mixed-mode Bond Elut Certify column that utilizes the characteristics of hydrophobic and polar interactions and ion exchange chromatography. Following extraction, cocaine, ecgonine methyl ester, benzoylecgonine, and cocaethylene were identified and quantitated using GC/MS.

The use of microcomputer-based psychomotor tests for the evaluation of benzodiazepine effects on human performance: a review with emphasis on temazepam.

1. The literature relating to the effects of benzodiazepines in general, and temazepam in particular, on human psychomotor performance as assessed using microcomputer-based testing batteries is surveyed. 2.

The effects of temazepam and ethanol on human psychomotor performance.

We have studied the effects of temazepam, alone and in combination with ethanol, on psychomotor performance in six healthy men and women using a battery of five microcomputer-based tasks before and 30, 90, and 150 min after treatment. The tests were pursuit tracking, divided attention, two four-choice reaction time tests and tapping rate. The entire battery required 25 min.

Evaluation of the Abbott ADx Amphetamine/Methamphetamine II abused drug assay: comparison to TDx, EMIT, and GC/MS methods.

Although the legitimate clinical use of amphetamine and amphetamine congeners is declining, the illicit use of these drugs remains high. There is a need for a rapid and conclusive method for detecting these compounds in routine urine drug testing, drug screening in drug rehabilitation centers, and as an aid in the diagnosis and treatment of potential overdoses. The Abbott ADx Amphetamine/Methamphetamine II assay (A/M II), a fluorescence polarization Immunoassay (FPIA), was compared to the Abbott TDx Amphetamine/Methamphetamine II assay (FPIA), the Syva enzyme-multiplied immunoassay technique (EMIT) and a gas chromatograph/mass spectrometry (GC/MS) method.

Determination of temazepam and temazepam glucuronide by reversed-phase high-performance liquid chromatography.

A rapid and sensitive method for extracting temazepam from human serum and urine is presented. Free temazepam is extracted from plasma and urine samples using n-butyl chloride with nitrazepam as the internal standard. Temazepam glucuronide is analyzed as free temazepam after incubating extracts with beta-glucuronidase.

Validation of two devices for evaluation of human psychomotor performance.

The Pursuit Meter III (PM III) and the Simultaneous Hand and Foot Tracking (SHAFT) task are microcomputer-based devices for the evaluation of human psychomotor performance. Both devices are pursuit-tracking tasks. The primary task (PM III) requires a subject superimpose a line over a computer-generated sine wave.

A modification and validation of two urine ethanol procedures for use with the Monarch 2000 Chemistry System.

A modification of two commercially available enzymatic ethanol urine assays for use with the Monarch 2000 Chemistry System (Instrumentation Laboratory) is described. Both the Syva EMIT st Urine Ethyl Alcohol Assay and the Sigma Diagnostics Alcohol in Urine Assay, which utilize the reduction of nicotinamide adenine dinucleotide (NAD) to NADH associated with the oxidation of ethanol in the presence of alcohol dehydrogenase (ADH), were adapted to spectrophotometrically determine ethanol concentration. Precision was evaluated over a 3-day period.

Application of the Syva EMIT and Abbott TDx amphetamine immunoassays to the detection of 3,4-methylene-dioxymethamphetamine (MDMA) and 3,4-methylene-dioxyethamphetamine (MDEA) in urine.

MDMA and MDEA are hallucinogenic analogs of amphetamine. The need for laboratory monitoring of these substances has developed as a result of their increased recreational use. Since the Abbott TDx and Syva EMIT-d.

Therapeutic effects of antimotion sickness medications on the secondary symptoms of motion sickness.

In addition to nausea and vomiting, motion sickness involves slowing of brain waves, loss of performance, inhibition of gastric motility and the Sopite Syndrome. The therapeutic effects of antimotion sickness drugs on these reactions were evaluated. The subjects were rotated to the M-III end-point of motion sickness.

Comparison of efficacy of ginger with various antimotion sickness drugs.

Unlabelled: Ginger and several other medications were compared with scopolamine and d-amphetamine for effectiveness in prevention of motion sickness.

Methods: Double-blind techniques were used. The subjects were given the medications two hours before they were rotated in a chair making head movements until a symptom total short of vomiting was reached.

Coronary arteriographic findings in cocaine abuse-induced myocardial infarction.

A 31-year-old black man was admitted with an acute anterior myocardial infarction 20 minutes after IV cocaine abuse. Cardiac catheterization showed a totally occluded left anterior descending artery. Intracoronary and intravenous streptokinase resulted in thrombolysis: repeat angiography showed a normal anterior descending.

Nuclear medicine evaluation of motion sickness and medications on gastric emptying time.

Diminished gastric motility and lack of bowel sounds have been observed in astronauts aboard the Space Shuttle (4). In this study subjects were given scopolamine 0.6 mg with d-amphetamine 5 mg with and without neostigmine 15 mg.

Mechanisms of antimotion sickness drugs.

Unlabelled: Eight subjects, male and female, were rotated using the step method to progressively increase the speed of rotation (+2 rpm) after every 40 head movements to a maximum of 35 rpm. The end-point for motion sickness was the Graybiel Malaise III total of symptoms short of frank nausea. The drug treatments were placebo, scopolamine 0.

The effect of antimotion sickness drugs on habituation to motion.

The effect of antimotion sickness drugs on habituation was studied. Subjects were rotated once a day for 5 d to the malaise III end-point after receiving placebo, 1 mg scopolamine, 10 mg d-amphetamine, or the combination of 0.6 mg scopolamine with 5 mg of d-amphetamine.

A thin layer chromatographic method for high volume screening of urine for methylphenidate abuse.

A thin layer chromatographic (TLC) method for the high volume screening of urine for methylphenidate (Ritalin) abuse is presented. The method utilizes charcoal extraction of ritalinic acid from urine and a simple test-tube methylation step for the conversion of the ritalinic acid to methylphenidate. The methylphenidate is then subjected to a routine TLC drug procedure for subsequent qualitative identification.