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BACKGROUND: The rising number of vancomycin-resistant enterococci (VREs) is a major concern to modern medicine because vancomycin is currently the 'last resort' drug for life-threatening infections. The D-alanyl-D-X ligases (where X is an hydroxy or amino acid) of bacteria catalyze a critical step in bacterial cell-wall peptidoglycan assembly. In bacteria that produce glycopeptide antibiotics and in opportunistic pathogens, including VREs, D-, D-ligases serve as switches that confer antibiotic resistance on the bacteria themselves. Peptidoglycans in vancomycin-sensitive bacteria end in D-alanyl-D-alanine, whereas in vancomycin-resistant bacteria they end in D-alanyl-D-lactate or D-alanyl-D-serine. RESULTS: We demonstrate that the selective utilization of D-serine by the Enterococcus casseliflavus VanC2 ligase can be altered by mutagenesis of one of two residues identified by homology to the X-ray structure of the Escherichia coli D-alanyl-Dalanine ligase (DdlB). The Arg322-->Met (R322M) and Phe250-->Tyr (F250Y) ligase mutants show a 36-44-fold decrease in the use of D-serine, as well as broadened specificity for utilization of other D-amino acids in place of D-serine. The F250Y R322M double mutant is effectively disabled as a D-alanyl-D-serine ligase and retains 10% of the catalytic activity of wild-type D-alanyl-D-alanine ligases, reflecting a 6,000-fold switch to the D-alanyl-D-alanine peptide. Correspondingly, the Leu282-->Arg mutant of the wild-type E. coli DdlB produced a 560-fold switch towards D-alanyl-D-serine formation. CONCLUSIONS: Single-residue changes in the active-site regions of D-, D-ligases can cause substantial changes in recognition and activation of hydroxy or amino acids that have consequences for glycopeptide antibiotic efficacy. The observations reported here should provide an approach for combatting antibiotic-resistant bacteria.  相似文献   

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Researchers have failed to establish infertility as a crisis or to identify an emotional reaction that is common to women who are faced with an inability to conceive. Many women, however, express a desire for counseling in conjunction with infertility treatment. This discrepancy in the research presents confusion for the clinician who is developing psychological interventions while working with infertile women. Infertility is approached in this article as a personal crisis that is based on a conflict between an ideal self as mother or woman and a real self as infertile. E. T. Higgins's (see record 1987-34444-001) self-discrepancy theory is proposed as a model for understanding the variability in the levels of distress and the types of emotional reactions to infertility. Clinical implications are discussed in relation to the variability of emotional reactions in female infertility clients, the selection of assessment techniques, and the selection of intervention techniques. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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OBJECTIVES: To examine the relative contributions of Executive Control Function (ECF), general cognition, mood, problem behavior, physical disability, demographic variables, and the number of prescribed medications to the level of care received by older retirees. DESIGN: Multivariate regression and discriminant modeling. SETTING: A single Continuing Care Retirement Community (CCRC) in San Antonio, Texas. PARTICIPANTS: A total of 107 older retirees (mean age = 83.7+/-7.2 years), including 17 community-dwelling, well, older controls and 90 CCRC residents. CCRC subjects represented a convenience sample of consecutive referrals for geropsychiatric assessment. Sixty-one subjects resided at a noninstitutionalized level of care, and 46 were institutionalized. MEASUREMENTS: Tests of ECF (the Executive Interview (EXIT25)), general cognition (the Mini-Mental State Examination (MMSE)), mood (the Geriatric Depression Scale short-form (sGDS)), problem behavior (the Nursing Home Behavior Problem Scale (NHBPS)), physical disability (the Cumulative Illness Rating Scale (CIRS)), age, gender, years of education, and the number of prescribed medications were studied. RESULTS: All variables except gender and education varied significantly across level of care. Four variables made significant independent contributions; EXIT25 score (r2 = .48, P< .001), medication usage (partial r2 = .11, P<.001), sGDS score (partial r2 = .06, P = .001), and problem behavior (partial NHBPS r2 = .04, P<.04). These variables accounted for 69% of the total variance in level of care (R2 = .69; F (df 7,99) = 32.1, P<.001). A discriminant model based on the number of prescribed medications, EXIT25, sGDS, and NHBPS scores classified 83.2% of cases correctly (Wilke's lambda = .50, F(5,101) = 20.1; P<.001). The MMSE enters but fails to contribute significantly, independent of the other variables. Age and CIRS scores fail to enter. CONCLUSIONS: Cognitive (particularly ECF) impairment contributes most to the observed variance in level of care received by older retirees in this CCRC. In contrast, markers of general cognition, depression, and physical illness contributed relatively little additional variance. ECF is not detected well by traditional cognitive measures and must be sought by specific tests. Further study is needed to replicate these findings in other populations.  相似文献   

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Ipriflavone, an isoflavone synthesized from the soy isoflavone daidzein, holds great promise in the prevention and treatment of osteoporosis and other metabolic bone diseases. It has been widely studied in humans and found effective for inhibiting bone resorption and enhancing bone formation, the net result being an increase in bone density and a decrease in fracture rates in osteoporotic women. While ipriflavone appears to enhance estrogen's effect, it does not possess intrinsic estrogenic activity, making it an attractive adjunct or alternative to conventional hormone replacement therapy. Preliminary studies have also found ipriflavone effective in preventing bone loss associated with chronic steroid use, immobility, ovariectomy, renal osteodystrophy, and gonadotrophin hormone-releasing hormone agonists. In addition, it holds promise for the treatment of other metabolic diseases affecting the bones, including Paget's disease of the bone, hyperparathyroidism, and tinnitus caused by otosclerosis.  相似文献   

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Investigated the relationship between manifest anxiety and religious conversion. 3 groups of 20 residents in a predominantly Protestant town were identified by the community's 2 ministers: (a) Ss having had a sudden religious conversion experience, (b) Ss having had a more gradual religious development, and (c) Ss who were not religious at all. The MA scale was administered to the members of each group. Group b and Group c did not differ significantly from each other on manifest anxiety, but Group a obtained significantly higher scores on the MA scale than the other 2 groups combined. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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This study elaborates our recent preliminary finding that vasoactive intestinal peptide (VIP) has a specific stimulatory effect on fetal rat Leydig cells. We examined the dose-response relationship for the effect of VIP on cAMP and testosterone production by dispersed fetal Leydig cells isolated from rat testes on embryonic day (E) 18.5. Further, we used RT-PCR to examine the expression of the VIP gene in fetal brain and testes and that of the VIP receptor genes in fetal testes and used RIA to measure VIP in testes and plasma during the fetal period. VIP stimulated fetal testicular cAMP production at a dose of 10(-9) mol/liter, whereas a dose as low as 10(-12) mol/liter stimulated testosterone production. This suggests that VIP at low doses may stimulate testosterone production using second messenger pathways other than cAMP. RT-PCR analysis could not reveal either VIP messenger RNA (mRNA) in fetal tissues or VIP1 receptor mRNA in the fetal or newborn testes, whereas VIP2 receptor mRNA was detected in fetal testes as early as E15.5. Northern hybridization analysis showed that the level of expression of VIP2 receptor mRNA is very low in fetal and neonatal testes and increases with age. The testicular VIP content was unmeasurable by our RIA method (i.e. <1 fmol/testis), whereas the circulating level of VIP was 82.9 +/- 1.1 pmol/liter on E17.5 and decreased with advancing fetal age. In conclusion, our results suggest that VIP from an extratesticular source, possibly from the maternal compartment, may regulate fetal testicular steroidogenesis through type 2 receptors as early as E15.5. These findings may be of physiological significance, because the onset of fetal testicular steroidogenesis occurs at an age (E15.5-19.5) before the onset of pituitary LH secretion.  相似文献   

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Chashchin  V. V. 《Metallurgist》2009,53(7-8):506-511
Metallurgist - More than half the thermal potential of the initial slab on a hot-strip mill is left in the finished coil of hotrolled strip, and extracting this energy as quickly as possible is an...  相似文献   

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The dorsal raphe nucleus (DRN) is an important nucleus in pain modulation. It has abundant 5-HT neurons and many other neurotransmitter and/or neuromodulator containing neurons. Its vast fiber connections to other parts of the central nervous system provide a morphological basis for its pain modulating function. Its descending projections, via the nucleus raphe magnus or directly, modulate the responses caused by noxious stimulation of the spinal dorsal horn neurons. In ascending projections, it directly modulates the responses of pain sensitive neurons in the thalamus. It can also be involved in analgesia effects induced by the arcuate nucleus of the hypothalamus. Neurophysiologic and neuropharmacologic results suggest that 5-HT neurons and ENKergic neurons in the DRN are pain inhibitory, and GABA neurons are the opposite. The studies of the intrinsic synapses between ENKergic neurons, GABAergic neurons, and 5-HT neurons within the DRN throw light on their relations in pain modulation functions, and further explain their functions in pain mediation.  相似文献   

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Fibrous histiocytoma has a variable, unpredictable behaviour and potential for malignancy. The treatment of choice is wide local excision, which, in the larynx, entails total laryngectomy. A case of fibrous histiocytoma of the larynx, treated successfully by radiotherapy, is presented. A recurrence was treated with cryosurgery and the patient is well at 10-year follow-up. The pathological characteristics of fibrous histiocytoma and the difficulties of classification are reviewed.  相似文献   

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A litterature review from 1986 to 1996 on medication use by older persons confirms previous conclusions on studies up to 1986 (Mishara and McKim, 1989): there is little empirical research on the role of family members in patterns of medication use by elders. This article briefly summarizes studies of factors related to medication use and prevention programs aimed at reducing problems related to compliance and drug adverse reactions in older persons. We propose a conceptual model of the role of the family as a component of resiliency of elders and we suggest that family members be included in strategies for preventing the risks related to inappropriate use of medicines.  相似文献   

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