Release of [3H]-acetylcholine from the isolated retina of the rat by potassium depolarization: dependence on high affinity choline uptake

1. The effect of potassium depolarization on the release of [3H]-acetylcholine ([3H]-ACh) from the isolated retina of the rat was studied. 2. Exposure of retinae to medium containing KCl (50 mM) evoked a large increase in the efflux of [3H]-ACh with only a small concurrent increase in the efflux of [3H]-choline. The KCl-evoked release of [3H]-ACh was almost abolished in calcium-free medium. 3. Incubation of retinae with [3H]-choline in sodium-free medium, or medium containing hemicholinum-3 (HC-3), procedures that are believed to inhibit selectively the high affinity choline transport system, reduced the retinal uptake of [3H]-choline by approximately 50% and the synthesis of [3H]-ACh by about 97%. 4. The potassium-evoked release of [3H]-ACh was almost abolished in retinae that had been loaded with [3H]-choline in sodium-free medium or medium containing HC-3, and subsequently superfused in normal medium. 5. It is suggested that as in other areas of the nervous system, a sodium-dependent, high affinity uptake system for choline is important in retinal cholinergic nerve terminals.     

Command, control and communication in bacterial pathogenesis

Family violence is typically progressive. As a man realizes the effectiveness of physical and emotional coercion, he tends to use it more frequently. In the face of imbalance of power in the relationship, a victim becomes more fearful, more submissive, and more likely to face serious injury. This is the first of a two-part series on physicians helping patients cope with domestic violence.     

New look at force-frequency relationship of human skeletal muscle: effects of fatigue

16-Fluoropalmitic acid was synthesized from 16-hydroxypalmitic acid using diethylaminosulfur trifluoride. This monofluorinated fatty acid then was used to make 1-palmitoyl-2-[16-fluoropalmitoyl]-phosphatidylcholine (F-DPPC) as a fluorinated analog of dipalmitoylphosphatidylcholine (DPPC). Surprisingly, we found that the phase transition temperature (Tm) of F-DPPC occurs near 50 degrees C, approximately 10 degrees C higher than its nonfluorinated counterpart, DPPC, as judged by both differential scanning calorimetry and infrared spectroscopy. The pretransition observed for DPPC is absent in F-DPPC. A combination of REDOR, rotational-echo double-resonance, and conventional solid-state NMR experiments demonstrates that F-DPPC forms a fully interdigitated bilayer in the gel phase. Electron paramagnetic resonance experiments show that below Tm, the hydrocarbon chains of F-DPPC are more motionally restricted than those of DPPC. X-ray scattering experiments confirm that the thickness and packing of gel phase F-DPPC is similar to that of heptanetriol-induced interdigitated DPPC. F-DPPC is the first phosphoglyceride containing sn-1 and sn-2 ester-linked fatty acyl chains of equal length that spontaneously forms interdigitated bilayers in the gel state in the absence of inducing agents such as alcohols.     

Neuronal signaling systems and ethanol dependence

In recent years there have been remarkable developments toward the understanding of the molecular and/or cellular changes in the neuronal second-messenger pathways during ethanol dependence. In general, it is believed that the cyclic adenosine 3',5'-monophosphate (cAMP) and the phosphoinositide (PI) signal-transduction pathways may be the intracellular targets that mediate the action of ethanol and ultimately contribute to the molecular events involved in the development of ethanol tolerance and dependence. Several laboratories have demonstrated that acute ethanol exposure increases, whereas protracted ethanol exposure decreases, agonist-stimulated adenylate cyclase activity in a variety of cell systems, including the rodent brain. Recent studies indicate that various postreceptor events of the cAMP signal transduction cascade (i.e., Gs protein, protein kinase A [PKA], and cAMP-responsive element binding protein [CREB]) in the rodent brain are also modulated by chronic ethanol exposure. The PI signal-transduction cascade represents another important second-messenger system that is modulated by both acute and chronic ethanol exposure in a variety of cell systems. It has been shown that protracted ethanol exposure significantly decreases phospholipase C (PLC) activity in the cerebral cortex of mice and rats. The decreased PLC activity during chronic ethanol exposure may be caused by a decrease in the protein levels of the PLC-beta 1 isozyme but not of PLC-delta 1 or PLC-gamma 1 isozymes in the rat cerebral cortex. Protein kinase C (PKC), which is a key step in the PI-signaling cascade, has been shown to be altered in a variety of cell systems by acute or chronic ethanol exposure. It appears from the literature that PKC plays an important role in the modulation of the function of various neurotransmitter receptors (e.g., gamma-aminobutyrate type A [GABAA], N-methyl-D-aspartate [NMDA], serotonin2A [5-HT2A], and 5-HT2C, and muscarinic [m1] receptors) resulting from ethanol exposure. The findings described in this review article indicate that neuronal-signaling proteins represent a molecular locus for the action of ethanol and are possibly involved in the neuro-adaptational mechanisms to protracted ethanol exposure. These findings support the notion that alterations in the cAMP and the PI-signaling cascades during chronic ethanol exposure could be the critical molecular events associated with the development of ethanol dependence.     

Prefrontal cortex involvement in selective letter generation: a functional magnetic resonance imaging study

Leech neurons exposed to salines containing inorganic Ca(2+)-channel blockers generate rhythmic bursts of impulses. According to an earlier model, these blockers unmask persistent Na+ currents that generate plateau-like depolarizations, each triggering a burst of impulses. The resulting increase in intracellular Na+ activates an outward Na+/K+ pump current that contributes to burst termination. We tested this model by examining systematically the effects of six transition metal ions (Co2+, Ni2+, Mn2+, Cd2+, La3+, and Zn2+) on the electrical activity of neurons in isolated leech ganglia. Each ion induced bursting activity, but the amplitude, form, and persistence of bursting differed with the ion used and its concentration relative to Ca2+. All ions tested suppressed chemical synaptic transmission between identified motor neurons, consistent with block of voltage-dependent Ca2+ currents in these cells. In addition, a strong correlation between suppression of synaptic transmission and burst amplitudes was obtained. Finally, burst duration was increased and the rate of repolarization decreased in reduced K+ saline, as expected for pump-dependent repolarization. These results provide further support for the hypothesis that a novel form of oscillatory electrical activity driven by persistent Na+ currents and the Na+/K+ pump occurs in leech ganglia exposed to Ca(2+)-channel blockers.     

Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP)

These revised recommendations of the Advisory Committee on Immunization Practices (ACIP) on measles, mumps, and rubella prevention supersede recommendations published in 1989 and 1990. This statement summarizes the goals and current strategies for measles, rubella, and congenital rubella syndrome (CRS) elimination and for mumps reduction in the United States. Changes from previous recommendations include: Emphasis on the use of combined MMR vaccine for most indications; A change in the recommended age for routine vaccination to 12-15 months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A recommendation that all states take immediate steps to implement a two dose MMR requirement for school entry and any additional measures needed to ensure that all school-aged children are vaccinated with two doses of MMR by 2001; A clarification of the role of serologic screening to determine immunity; A change in the criteria for determining acceptable evidence of rubella immunity; A recommendation that all persons who work in health-care facilities have acceptable evidence of measles and rubella immunity; Changes in the recommended interval between administration of immune globulin and measles vaccination; and Updated information on adverse events and contraindications, particularly for persons with severe HIV infection, persons with a history of egg allergy or gelatin allergy, persons with a history of thrombocytopenia, and persons receiving steroid therapy.     

Endovascular occlusion with a new mechanical detachable coil

OBJECTIVE: Metallic coils have been used for vascular embolization for many years but controlled-release coils have only recently become commercially available. Most of these devices are microcoils that were manufactured primarily for the packing of intracerebral aneurysms; therefore, they lack radial force and are not ideal agents for the occlusion of high-flow lesions such as pulmonary arteriovenous malformations (PAVMs). The objective of this study was to review our experience with a new detachable coil based on the conventional Gianturco-Wallace coil. SUBJECTS AND METHODS: The new detachable coil was initially used for the treatment of varicocele in 20 patients. Subsequently, the coil was used in 48 patients during 90 procedures for the treatment of PAVMs. RESULTS: A total of 548 coils were used. Complete occlusion of the testicular vein was achieved in all patients with varicocele. Successful occlusion of the PAVM being treated was achieved in all patients, and no instances of recanalization were documented in any of the patients who returned for follow-up angiography. Forty-one coils had to be removed completely from the catheter before detachment because of inappropriate size or position. Eight coils failed to detach easily, and six of these had to be removed. Most of these device failures were associated with kinking of the screw thread mechanism between the coil and the delivery wire. CONCLUSION: The Jackson detachable coil allows safer, more accurate, and more distal embolization of PAVMs than is possible with nondetachable coils. Complications associated with its use have been few.