Traffic of dynamin within individual Drosophila synaptic boutons relative to compartment-specific markers

Presynaptic terminals contain several specialized compartments, which have been described by electron microscopy. We show in an identified Drosophila neuromuscular synapse that several of these compartments-synaptic vesicle clusters, presynaptic plasma membrane, presynaptic cytosol, and axonal cytoskeleton-labeled by specific reagents may be resolved from one another by laser scanning confocal microscopy. Using a panel of compartment-specific markers and Drosophila shibire(ts1) mutants to trap an intermediate stage in synaptic vesicle recycling, we have examined the localization and redistribution of dynamin within single synaptic varicosities at the larval neuromuscular junction. Our results suggest that dynamin is not a freely diffusible molecule in resting nerve terminals; rather, it appears localized to synaptic sites by association with yet uncharacterized presynaptic components. In shi(ts1) nerve terminals depleted of synaptic vesicles, dynamin is quantitatively redistributed to the plasma membrane. It is not, however, distributed uniformly over presynaptic plasmalemma; instead, fluorescence images show "hot spots" of dynamin on the plasma membrane of vesicle-depleted nerve terminals. We suggest that these dynamin-rich domains may mark the active zones for synaptic vesicle endocytosis first described at the frog neuromuscular junction.     

An unjustified, sweeping indictment by Motta et al. of human figure drawings for assessing psychological functioning.

Comments on R. W. Motta et al's (see record 1994-04005-001) conclusion that the use of human figure drawings (HFDs) in psychological testing is invalid. Motta et al completely ignore strong positive evidence that narrowly prescribed uses of HFD are valid for assessing certain aspects of personality and intellectual functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sudden incapacitation: USAF experience, 1970-80

During the period 1970-80, there were reported 146 cases of in-flight sudden incapacitation in the USAF. Of these, 62 involved pilots, 14 were navigators, and 70 were student pilots. The etiologies of sudden incapacitation included illness without loss of consciousness, loss of consciousness, spatial disorientation, and improper M-1 maneuver. Each of these categories is analyzed with emphasis upon prevention, for example, not flying with symptomatic preexisting disease, continued emphasis upon spatial disorientation training, and correct performance of the M-1 maneuver. Based upon the data, conclusions and recommendations are suggested to minimize the risk of episodes of in-flight sudden incapacitation.     

Effects of phentermine on responding maintained under multiple fixed-ratio schedules of food and cocaine presentation in the rhesus monkey

Drugs that decrease drug-maintained responding at doses that do not decrease other behaviors in animals may be suitable candidates for development as medications to treat drug abuse in humans. The present study examined whether this effect could be obtained with phentermine, a drug that has been reported to decrease cocaine intake in humans. Rhesus monkeys were trained under multiple fixed-ratio 30-response schedules of food and i.v. cocaine delivery. Phentermine was always given as a slow, i.v. infusion. Acute treatment with phentermine (0.3-10 mg/kg) decreased cocaine-maintained responding at doses that did not decrease, or decreased less, food-maintained responding for each of three unit doses of cocaine (10-100 microg/kg/injection). Subacute treatment with phentermine (3 or 5.6 mg/kg, daily) also decreased cocaine-maintained responding more than food-maintained responding. After subacute treatment was terminated, rates of cocaine-maintained responding generally recovered to levels comparable to those seen during untreated control sessions. Phentermine (0.3-3 mg/kg) did not generally increase responding associated with a very low (1 microg/kg/injection) unit dose of cocaine, suggesting that the decrease in cocaine-maintained responding at higher unit doses was not the result of a leftward shift in the cocaine unit dose-effect function. Phentermine (0.1-3 mg/kg) decreased responding maintained by 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine (GBR 12909) (30 microg/kg/injection) at doses similar to those that decreased food-maintained responding. These results show that phentermine is effective in decreasing cocaine self-administration and suggest that it may be an effective medication for cocaine abuse.     

The Drug Evaluation Classification Program: using ocular and other signs to detect drug intoxication

BACKGROUND: A systematic approach to determining drug intoxication has been developed for use by police officers. By considering specific physiological signs, trained officers can detect the effects of seven major drug types. METHODS: Officers follow a 12-step testing sequence and evaluate signs such as pupil sizes and responses, eye movements, heart rate, body temperature, mental timing, and balance. A matrix is then used to compare that subject's signs to those that would be produced by the seven types of drugs. If a pattern match is found, the officer concludes that the subject is under the influence of a drug and specifies the drug type. RESULTS: Several field and laboratory validation studies have been conducted using these procedures. In general, officers were 70% to 90% accurate in determining intoxication status and drug classification, but poly-drug use and drug rebound effects can sometimes cause problems in interpretation. CONCLUSION: Ocular and other physiological signs can be used to detect drug intoxication and classify the type of drug taken. Knowledge of the procedures used in the Drug Recognition Program can enable optometrists to serve as consultants to the police and as expert witnesses in cases involving the use of ocular signs that indicate illicit drug use.     

Pharmacological inhibition of protein kinases in intact cells: antagonism of beta adrenergic receptor ligand binding by H-89 reveals limitations of usefulness

The use of pharmacological inhibitors of protein kinases represents a potentially powerful tool in dissecting the regulatory features of intracellular signaling pathways. However, although the in vitro potency, selectivity, and efficacy of numerous kinase inhibitors have been characterized, little is known regarding the usefulness of these compounds as inhibitors in intact cells. In attempting to characterize the role of protein kinase A (PKA) in regulating the beta-2 adrenergic receptor (AR) in human airway cells, we observed a seemingly profound capacity of the isoquinoline H-89, a potent and widely used PKA inhibitor, to attenuate agonist-mediated desensitization of the beta-2 AR. Although additional experiments identified H-89 as an effective inhibitor of intracellular PKA, extended analysis of the compound determined the principal effect of H-89 was via its action as a beta-2 AR antagonist. Pretreatment with or the acute addition of H-89 significantly attenuated isoproterenol-stimulated cAMP accumulation. In cells pretreated with H-89 and then washed extensively, the subsequent dose-dependent response to isoproterenol suggested beta-2 AR antagonism by retained H-89. Competition binding of [125I]iodopindolol established Ki values of approximately 180 nM and 350 nM for H-89 antagonism of beta-2 AR and beta-1 AR, respectively. Additional receptor binding studies suggest selectivity of H-89 for the beta-2 AR and beta-1 AR, although a weak antagonism (Ki values of approximately 10 microM or greater) of other G protein-coupled receptors was observed. Results from additional pharmacological and biochemical analyses of various protein kinase inhibitors further established the need for careful characterization of pharmacological inhibitors when used in intact cell models.