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Our previous studies have established that a cell-surface 25-kDa elastin-binding protein of Staphylococcus aureus (EbpS) mediates binding of this pathogen to the extracellular matrix protein elastin. Results from binding assays examining the activity of various EbpS fragments suggested that the elastin recognition domain is contained within the first 59 amino acids. In this report, we have used functional analyses with synthetic peptides and recombinant truncated forms of EbpS to localize the elastin binding domain to a 21-amino acid region contained within residues 14-34 of EbpS. Further evidence for the importance of this domain was obtained by demonstrating that the inhibitory activity of anti-EbpS antibodies on staphylococcal elastin binding was neutralized when these antibodies were pre-absorbed with a truncated recombinant EbpS construct containing residues 1-34. Overlapping synthetic peptides corresponding to EbpS residues 14-36 were then generated and tested for elastin binding activity to define further the elastin binding domain, and results from these studies showed that sequences spanning amino acids Gln14-Asp23, Asp17-Asp23, and Thr18-Glu34 inhibit binding of Staphylococcus aureus to elastin. Our analyses indicate that the hexameric sequence Thr18-Asn-Ser-His-Gln-Asp23 is the minimal sequence common to all active synthetic peptides, proteolytic fragments, and recombinant constructs of EbpS. Furthermore, substitution of Asp23 with Asn abrogated the blocking activity of the synthetic peptides, demonstrating the requirement for a charged amino acid at this location. The composite data indicate that staphylococcal elastin binding is mediated by a discrete domain defined by short peptide sequences in the amino-terminal extracellular region of EbpS. 相似文献
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The ultrasonographic diagnosis of cerebral ventriculomegaly carries grave implications, in that affected fetuses may suffer abnormal postnatal development or therapeutic abortion. It is important for pathologists to corroborate the clinical diagnosis, but because diagnostic methodologies and criteria differ so radically, this can be problematic. The clinical diagnosis is made primarily by serial ultrasound examinations of the cerebral ventricles, spaces that can be altered postmortem, particularly when the brain is autolysed or deformed artifactually. We therefore sought to learn if examination of tissue, rather than spaces, can identify accurately those fetuses diagnosed with cerebral ventriculomegaly by prenatal ultrasound. The thickness of the cerebral mantle was obtained in 100 control fetuses aged 14 to 26 postmenstrual weeks. Statistical analysis revealed significant correlation of cerebral mantle thickness with crown-rump length, foot length, and head circumference. Twenty fetuses diagnosed with ventriculomegaly showed mantle thicknesses that were less than the control mean. In a few cases, mantle thickness fell between the mean and -1 SD; in several others, thickness was diminished by -1 SD to -2 SD; in one-half of cases, mantle thickness was 2 SDs or more below the expected mean. Head circumference was within 2 SDs of the control mean in most cases, and increased beyond 2 SDs in only two cases. Head circumference is an unreliable indicator of ventriculomegaly in the midgestational fetus. By contrast, cerebral mantle thickness is a simple and useful way of corroborating ultrasonographic diagnoses at autopsy and may also prove useful in clinical settings. 相似文献
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Role of maintenance treatment in opioid dependence 总被引:3,自引:0,他引:3
Methadone maintenance treatment (MMT) involves the daily administration of the oral opioid agonist methadone as a treatment for opioid dependence-a persistent disorder with a substantial risk of premature death. MMT improves health and reduces illicit heroin use, infectious-disease transmission, and overdose death. However, its effectiveness is compromised if low maintenance doses of methadone (<60 mg) are used and patients are pressured to become prematurely abstinent from methadone. Pregnancy and psychiatric comorbidity are not contraindications for MMT. As an alternative to MMT, other oral opioid agents (eg, naltrexone, buprenorphine) may increase patient choice and avoid some of the more unpleasant aspects of MMT. The public-health challenge for the future is to develop and continue to deliver safe and effective forms of opioid maintenance treatment to as many opioid-dependent individuals as can benefit from them. 相似文献
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HA Kazakova NS Entelis RP Martin IA Tarassov 《Canadian Metallurgical Quarterly》1999,442(2-3):193-197
The effect of quinine, a cinchona alkaloid, was studied on gastrointestinal transit in mice. Intraperitoneal (i.p.) administration of quinine inhibited the intestinal propulsion of a charcoal suspension at a dose of 100 mg/kg, comparing favorably with 5 mg/kg morphine. In an attempt to probe into the mechanism underlying this inhibition, a possible modulation by minoxidil (1 mg/kg, p.o.) and glibenclamide (1 mg/kg, p.o.), the drugs that, respectively, open and close ATP-sensitive K+ channels was tested on gastrointestinal transit in animals treated or not with quinine or morphine. While minoxidil produced no significant change of normal transit, glibenclamide significantly increased it. However, both drugs blocked the quinine-induced reduction in gastrointestinal transit. In contrast, the inhibitory effect of morphine on gastrointestinal transit was not modified by either drug. The effects of quinine as well as of morphine on gastrointestinal transit were significantly antagonized by naloxone (2 mg/kg, s.c.), a mu-opioid receptor antagonist but not by yohimbine (1 mg/kg, i.p.), an alpha2-adrenoceptor antagonist. Furthermore, quinine at a lower dose (25 mg/kg) that showed no per se effect on gastrointestinal transit, significantly potentiated the response to 2.5 mg/kg morphine. Although the role of ATP-sensitive K+ channels in the action of quinine and morphine was not clarified by the present results, a possible involvement of endogenous opioid(s) in the quinine-induced inhibition of gastrointestinal transit can be suggested. 相似文献