The discriminative stimulus effects of ethanol are mediated by NMDA and GABAA receptors in specific limbic brain regions

 This study was conducted to assess the involvement of N-methyl-d-aspartate (NMDA) and γ-aminobutyric acid (GABA) receptor systems, located in specific limbic brain regions, in the discriminative stimulus effects of ethanol. Male Long-Evans rats were trained to discriminate between intraperitoneal (IP) injections of ethanol (1 g/kg) and saline on a two-lever drug discrimination task. The rats were then implanted with bilateral injector guides aimed at the nucleus accumbens core (AcbC), prelimbic cortex (PrLC), hippocampus area CA1 (CA1), or extended amygdala (i.e., at the border of the central and basolateral nuclei). Infusions of the non-competitive NMDA antagonist MK 801 in the AcbC or CA1 resulted in dose-dependent full substitution for IP ethanol. MK 801 infusion in the PrLC or amygdala failed to substitute for ethanol. Injection of the competitive NMDA antagonist CPP in the AcbC also failed to substitute for ethanol. Co-infusion of MK 801 in the hippocampus potentiated the effects of MK 801 in the AcbC, whereas NMDA infusion in the hippocampus attenuated the ability of MK 801 in the AcbC to substitute for ethanol. The direct GABA_A agonist muscimol resulted in dose-dependent full substitution for IP ethanol when it was injected into the AcbC or amygdala, but failed to substitute when administered in the PrLC. Co-infusion of MK 801, but not CPP, potentiated the effects of muscimol in the AcbC. These results demonstrate that ethanol’s discriminative stimulus function is mediated centrally by NMDA and GABA_A receptors located in specific limbic brain regions. The data also suggest that the discriminative stimulus effects of ethanol are mediated by interactions between ionotropic GABA_A and NMDA receptors in the nucleus accumbens, and by interactions among brain regions. Received: 2 December 1997 / Final version: 24 January 1998     

Emphysema of early onset associated with a complete deficiency of alpha-1-antitrypsin (null homozygotes)

We have compared lung function in 3 subjects with no alpha 1-antitrypsin (alpha 1-protease inhibitor) (null homozygotes) with subjects having the typical deficiency, PIZZ. We identified a 31-yr-old woman, presenting with severe obstructive lung disease, who had no detectable plasma alpha 1-antitrypsin, indicating homozygosity for a "null" (or PI*QO) allele of alpha 1-antitrypsin. Two of her sisters have a similar deficiency, one with an onset of symptoms at 17 yr of age. Because of the likelihood that there are a number of different PI*QO alleles, the type in this family has been named null Mattawa (QOmattawa). All 3 homozygotes have shown a marked deterioration of lung function over a 7-yr period of follow-up. In contrast, lung function tests of 6 age-matched nonsmoking subjects with alpha 1-antitrypsin deficiency, PI type ZZ, showed no abnormalities of lung function. The 15 to 20% of the normal plasma concentration of alpha 1-antitrypsin associated with the PI*Z allele appears to provide some protection to the lung in comparison with a complete deficiency state.     

Infection of catheterised patients: bacterial colonisation of encrusted Foley catheters shown by scanning electron microscopy

Summary The surfaces of 32 encrusted urinary catheters were examined by scanning electron microscopy to investigate the association of bacteria with the encrusting deposits. Deposits consisted of struvite crystals surrounded by aggregates of very small crystallites of hydroxyapatite. Underneath these minerals there was a layer of closely packed bacteria. Impressions of bacteria were also observed in hydroxyapatite. Crystals were often engulfed by the bacterial layer, which thus appeared to bind the crystals to each other and to the catheter surface. This thick layer of bacteria associated with crystals may protect both the bacteria from antibiotics and the crystals from acidic bladder washout solutions intended to dissolve them. Furthermore, the existence of this sessile population explains why urease-producing bacteria are not invariably detected in the urine of patients with encrusted catheters. The observation of this bacterial layer (or biofilm) by scanning electron microscopy provided direct evidence for infection being implicated in catheter encrustation.     

'Breaking' position-invariant object recognition

While it is often assumed that objects can be recognized irrespective of where they fall on the retina, little is known about the mechanisms underlying this ability. By exposing human subjects to an altered world where some objects systematically changed identity during the transient blindness that accompanies eye movements, we induced predictable object confusions across retinal positions, effectively 'breaking' position invariance. Thus, position invariance is not a rigid property of vision but is constantly adapting to the statistics of the environment.     

Distribution of glucose incorporated into macromolecular material by treponema pallidum.

Treponema pallidum was observed to incorporate glucose carbons into lipids, ribonucleic acid, deoxyribonucleic acid, and protein. Only the glycerol portions of phosphatidylcholine and phosphatidylglycerol contained glucose-derived carbons. Incorporation of exogenous choline into phosphatidylcholine was detected. Glucose was incorporated into only the pentoses of nucleic acids. About 50% of the glucose incorporated into protein was present in only one amino acid, aspartate. Evidence suggests that aspartate synthesis could follow the conversion of phosphoenolpyruvate to oxalacetic acid by a guanosine 5'-diphosphate-dependent phosphoenolpyruvate carboxykinase.     

Arterial wall properties and dietary atherosclerosis in the racing greyhound.

The effects of experimental (dietary) atherosclerosis on arteries from racing greyhounds were studied. Measurements of pressure and external diameter were made on islated carotid and iliac arteries under active (norepinephrine, 5 microgram/ml) and passive (zero Ca2+ and 2 mM EGTA) smooth muscle conditions. Iliac arteries from diet-fed animals demonstrated substantial intimal lesions, but the carotid arteries were usually grossly involved. Arteries from atherosclerotic animals were stiffer during passive conditions, with the iliac arteries having the greater changes. In iliac arteries from treated animals, collagen and elastin contents were decreased, and the collagen-to-elastin ratio was increased; in carotid arteries from treated animals, elastin content was increased and the collagen-to-elastin ratio was decreased. The maximum range of control of arterial wall mechanics by smooth muscle was diminished in treated iliacs but unchanged in carotids. Both force development and constriction responses associated with smooth muscle activation were diminished in treated iliacs but unchanged in treated carotids. Mechanical properties of series elastic elements in treated iliacs were stiffer, but treated carotids were unchanged.