Resistance to quinupristin-dalfopristin due to mutation of L22 ribosomal protein in Staphylococcus aureus

The mechanism of resistance to the streptogramin antibiotics quinupristin and dalfopristin was studied in a Staphylococcus aureus clinical isolate selected under quinupristin-dalfopristin therapy, in four derivatives of S. aureus RN4220 selected in vitro, and in a mutant selected in a model of rabbit aortic endocarditis. For all strains the MICs of erythromycin, quinupristin, and quinupristin-dalfopristin were higher than those for the parental strains but the MICs of dalfopristin and lincomycin were similar. Portions of genes for domains II and V of 23S rRNA and the genes for ribosomal proteins L4 and L22 were amplified and sequenced. All mutants contained insertions or deletions in a protruding beta hairpin that is part of the conserved C terminus of the L22 protein and that interacts with 23S rRNA. Susceptible S. aureus RN4220 was transformed with plasmid DNA encoding the L22 alteration, resulting in transformants that were erythromycin and quinupristin resistant. Synergistic ribosomal binding of streptogramins A and B, studied by analyzing the fluorescence kinetics of pristinamycin I(A)-ribosome complexes, was abolished in the mutant strain, providing an explanation for quinupristin-dalfopristin resistance.     

APOE ��4 allele and CSF APOE on Cognition in HIV-Infected Subjects

The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects on brain function due to the presence of APOE ??4 allele(s) in HIV-infected patients are unknown. However, APOE ??4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection. Here, we show further evidence for the role of APOE ??4 in promoting cognitive impairment. We measured the APOE levels in the CSF of HIV-infected individuals. HIV+ subjects showed lower CSF APOE proteins than SN controls (?19%, p?=?0.03). While SN subjects with or without ??4 allele showed no difference in CSF APOE levels, ??4+ HIV+ subjects had similar levels to the SN subjects but higher levels than ??4? HIV+ subjects (+34%, p?=?0.01). Furthermore, while HIV+ subjects with ??2 or ??3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r?=?+0.35, p?=?0.05), ??4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r?=??0.61, p?=?0.02), had lower Global Cognitive Scores (r?=??0.57, p?=?0.03), and had poorer performance on tests involving learning (??4 allele x [APOE] interaction, p?=?0.01). Our findings also suggest that the relatively higher levels of CSF APOE in ??4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the ??4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.     

伴近视的鞍区肿瘤眼部病变特点

目的：探讨近视患者的鞍区肿瘤眼部病变的临床特点。方法：回顾分析了18例伴近视的鞍区肿瘤的视力、视野及眼底等情况。结果：18例初诊时,19眼（占52.8%）视力低下4.0,仅5例（占27.8%）视野缺损呈典型的视交性单、双颞侧偏盲,10例（占55.6%）双眼视神经不同程度萎缩,4例（占22.2%）单眼视神经萎缩。结论：伴近视的鞍区肿瘤眼部病变常很严重,容易被误诊为青光眼性视神经萎缩,视乳头炎、缺血性视神经病变。     

Preliminary note on biometric data relating to the human coraco-acromial arch

A biometric study based on 20 human scapulae made it possible to specify the variations in the gap of the coraco-acromial arch in relation to its depth and height. A graphic representation in rectangular coordinates, then in spatial representation in relation to the three planes of reference, leads to the following findings: the bony variations in the arch occur essentially: at the coracoid apophysis, and two types of arch can be distinguished depending on the predominance of bony or of ligamentous components.     

Investigation of behavioral and electrophysiological responses induced by selective stimulation of CCKB receptors by using a new highly potent CCK analog, BC 264

The new CCKB analog, Boc-Tyr (SO3H)-gNle-mGly-Trp-(NMe)-Nle-Asp-PheNH2 (BC 264) exhibited a high affinity (KI = 0.39 +/- 0.15 nM) and selectivity for central (B) versus peripheral (A) receptors (KI CCKA/KI CCKB = 910) in the rat. In agreement with these binding studies, BC 264 was at least 50 times more potent than CCK8 in stimulating the firing of rat CA hippocampal neurones. Furthermore stereotaxic injection of BC 264 or CCK8 in the VTA of rats resulted in potentiation of the dopamine-induced hypolocomotion. These two types of CCK8 responses have been previously shown in involve CCKB receptors. In contrast, after administration into the postero-median nucleus accumbens, the hypoexploration, the increase of emotionality of rats, or the potentiation of dopamine-induced hyperlocomotion were obtained after injection of CCK8 but not of BC 264, supporting the involvement of peripheral CCKA receptors in these CCK8 responses. Owing to its resistance to peptidases, BC 264 appears to be of great interest in the investigation of the still uncertain functional roles of CCK in the central nervous system.     

Electrophysiological identification of mesencephalic ventromedial tegmental (VMT) neurons projecting to the frontal cortex, septum and nucleus accumbens

The electrophysiological properties of neurons located in the mesencephalic ventromedial tegmentum (VMT) and the organization of the efferents of these neurons to the frontal cortex, the septum, the nucleus accumbens and the head of the striatum were studied in ketamine-anesthetized rats. The projections of the VMT cells were determined through use of the antidromic activation method. Our results show that VMT projections to different target areas originate mainly from different VMT neurons. However, in some cases single VMT neurons were found to send axon collaterals to two different areas. Three branching patterns were observed: septum-cortex, septum--nucleus accumbens and septum--striatum. The occasional observation of temporally distinct antodromic responses from a single area was considered to result from activation of different branches of the arborizing axon. The distribution of antidromic response latencies for VMT projections to each structure is discussed in relation to the question of dopaminergic versus non-dopaminergic mesolimbic and mesocortical systems.