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.     

A genomic analysis of chicken cytokines and chemokines.

As most mechanisms of adaptive immunity evolved during the divergence of vertebrates, the immune systems of extant vertebrates represent different successful variations on the themes initiated in their earliest common ancestors. The genes involved in elaborating these mechanisms have been subject to exceptional selective pressures in an arms race with highly adaptable pathogens, resulting in highly divergent sequences of orthologous genes and the gain and loss of members of gene families as different species find different solutions to the challenge of infection. Consequently, it has been difficult to transfer to the chicken detailed knowledge of the molecular mechanisms of the mammalian immune system and, thus, to enhance the already significant contribution of chickens toward understanding the evolution of immunity. The availability of the chicken genome sequence provides the opportunity to resolve outstanding questions concerning which molecular components of the immune system are shared between mammals and birds and which represent their unique evolutionary solutions. We have integrated genome data with existing knowledge to make a new comparative census of members of cytokine and chemokine gene families, distinguishing the core set of molecules likely to be common to all higher vertebrates from those particular to these 300 million-year-old lineages. Some differences can be explained by the different architectures of the mammalian and avian immune systems. Chickens lack lymph nodes and also the genes for the lymphotoxins and lymphotoxin receptors. The lack of functional eosinophils correlates with the absence of the eotaxin genes and our previously reported observation that interleukin- 5 (IL-5) is a pseudogene. To summarize, in the chicken genome, we can identify the genes for 23 ILs, 8 type I interferons (IFNs), IFN-gamma, 1 colony-stimulating factor (GM-CSF), 2 of the 3 known transforming growth factors (TGFs), 24 chemokines (1 XCL, 14 CCL, 8 CXCL, and 1 CX3CL), and 10 tumor necrosis factor superfamily (TNFSF) members. Receptor genes present in the genome suggest the likely presence of 2 other ILs, 1 other CSF, and 2 other TNFSF members.     

Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer

Optical technologies, such as reflectance and fluorescence spectroscopy, have shown the potential to provide improved point-of-care detection methods for cervical neoplasia that are sensitive, specific, and cost-effective. Our specific goals are to analyze the diagnostic potential of reflectance and fluorescence spectra, alone and in combination, to discriminate normal and precancerous cervical tissue in vivo and to identify which classification features contain significant diagnostic information. Reflectance spectra are measured at four source-detector separations and fluorescence emission spectra are measured at 16 excitation wavelengths, from 324 sites in 161 patients. These 20 spectral features are permuted in all possible combinations of one, two, and three; and classification algorithms are developed to evaluate the diagnostic performance of each combination. Algorithms based on fluorescence spectra alone yield better diagnostic performance than those based on reflectance spectra alone. The combination of fluorescence and reflectance do not significantly improve diagnostic performance compared to fluorescence alone, except in the case of discriminating high-grade precancers from columnar normal tissue. In general, fluorescence emission spectra at 330- to 360-nm and 460- to 470-nm excitation provide the best diagnostic performance for separating all pairs of tissue categories.     

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.