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1.
E. Wieczerzak E. Jankowska S. Rodziewicz‐Motowido A. Giedo J. giewka Z. Grzonka M. Abrahamson A. Grubb D. Brmme 《Chemical biology & drug design》2005,66(Z1):1-11
Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, Ki, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K. 相似文献
2.
Clinical aspects of pelvic inflammatory disease 总被引:2,自引:0,他引:2
Pelvic inflammatory disease (PID) is a common and poorly managed condition.
Untreated or inadequately treated, it leads to tubal infertility, ectopic
pregnancy and chronic pelvic pain. Diagnostic difficulties are compounded
by the wide variety of clinical presentations and the insensitivity and
poor specificity of laboratory tests. Better recognition of mild and
atypical disease needs a high index of suspicion whenever young, sexually
active women present with gynaecological symptoms. Laparoscopy supplemented
by microbiological tests and fimbrial minibiopsy should be regarded as the
diagnostic 'gold standard' for research studies; new studies are required
to identify techniques which might reduce under- and over-diagnosis. Early
treatment reduces the risk of an adverse effect on fertility. Any
therapeutic regimen selected should be effective against the common
aetiological agents Chlamydia trachomatis, Neisseria gonorrhoeae, genital
mycoplasmas and aerobic and anaerobic bacteria. Since at least 60% of cases
of PID can be attributed to infection with a sexually transmitted organism,
partner notification forms an essential part of management.
相似文献
3.
4.
Laparoscopic Cholecystectomy for Acute Cholecystitis: Prospective Trial 总被引:23,自引:0,他引:23
Samuel Eldar Edmond Sabo Ernest Nash Jack Abrahamson Ibrahim Matter 《World journal of surgery》1997,21(5):540-545
p
< 0.00001) and for hydrops (28.5%) and empyema of the gallbladder
(28.5%) (
p
= 0.004). The difference in conversion
between the group with acute necrotizing (gangrenous) cholecystitis and
the two groups with hydrops and empyema of the gallbladder was not
statistically significant (
p
= 0.07). The complication
rates of acute cholecystitis, hydrops, empyema of the gallbladder, and
gangrenous cholecystitis were 9.0%, 9.5%, 14.0%, and 20.0%,
respectively (
p
= NS). Patients with an operative
delay of 96 hours or less from the onset of acute cholecystitis had a
conversion rate of 23%, whereas a delay of more than 96 hours was
associated with a conversion rate of 47% (
p
= 0.022).
The complication rate was 8.5% in the laparoscopic group and 27% in
the converted group (
p
= 0.013). Patients over 65
years of age, with a history of biliary disease, a nonpalpable
gallbladder, WBC count over 13,000/cc, and acute gangrenous
cholecystitis were independently associated with a high LC conversion
rate; male patients, finding large bile stones, serum bilirubin over
0.8 mg/dl, and WBC count over 13,000/cc were independently associated
with a high complication rate following laparoscopic surgery with or
without conversion. Generally, LC can be performed safely for acute
cholecystitis, with acceptably low conversion and complication rates.
Different forms of cholecystitis carry various conversion and
complication rates in selected cases. LC for acute cholecystitis should
be performed within 96 hours of the onset of disease. Predictors of
conversion and complications may be helpful when planning the
laparoscopic approach to acute cholecystitis. 相似文献
5.
Screening for early ovarian cancer 总被引:5,自引:0,他引:5
6.
7.
Purified Pseudomonas aeruginosa elastase and alkaline protease rapidly cleaved soluble laminin, with each enzyme yielding different cleavage products. These cleavage fragments were separated from the intact laminin A and B polypeptide chains by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis and detected by their characteristic Coomassie blue staining patterns. Pseudomonas elastase produced rapid and extensive degradation of both A and B chains, including the disulfide-rich regions. Apparently complete degradation to limit digests was obtained after 30 min with a substrate/enzyme ratio of 30:0.5. Under similar conditions, alkaline protease rapidly degraded the A chain while slowly degrading the B chain. In addition, immunoreactive laminin was released from authentic basement membranes after incubation with either enzyme as detected by an enzyme-linked immunoabsorption assay and by immunofluorescence. The results from these studies suggest a direct role for elastase and alkaline protease in both tissue invasion and hemorrhagic tissue necrosis in P. aeruginosa infections. 相似文献
8.
Continuing medical education for life: eight principles. 总被引:1,自引:0,他引:1
S Abrahamson J Baron A S Elstein W P Hammond G B Holzman B Marlow M S Taggart J Schulkin 《Academic medicine》1999,74(12):1288-1294
Continuing medical education (CME) is being pressured to change in response to increasing and changing educational needs of practicing physicians, fostered by technical innovations, evolution of practice styles, and the reorganization of health care delivery. Leadership in the reform of CME falls primarily to the medical specialty societies in light of their traditional responsibilities for accrediting CME and maintaining professional standards. To address the need for reform, the American College of Obstetricians and Gynecologists in 1997 organized a conference to assemble CME program administrators from several medical specialties and academicians with expertise in postgraduate learning. At the conference, issues facing CME were examined. The authors, who were conference participants, state and explain eight principles that emerged from conference discussions. (For example: "Educational activities should be supportive of and coordinated with the transition to evidence-based medicine.") The principles reflect the interspecialty and interdisciplinary consensus achieved by the conference participants and can serve as useful guideposts for educators as they work to improve CME in their institutions. The authors conclude by noting the need for a more systematic and rigorously analytic approach, where CME content is determined according to assessed needs and CME is evaluated by measuring outcomes; for this to happen, CME educators and faculty must be brought up to date through training, including the use of problem-based learning. CME must also instill collegiality, interaction, and collaboration into the learning environment instead of being a solitary learning activity. Finally, CME must not only emphasize the acquisition of knowledge but also instruct physicians in the process of decision making to help them better use their knowledge as they make clinical judgments. 相似文献
9.
10.
Glomerular basement membrane expansion in passive Heymann nephritis. Absence of increased synthesis of type IV collagen, laminin, or fibronectin. 总被引:1,自引:2,他引:1 下载免费PDF全文
M. A. Fogel C. D. Boyd V. Leardkamolkarn D. R. Abrahamson A. W. Minto D. J. Salant 《The American journal of pathology》1991,138(2):465-475
The distribution and synthetic rate of glomerular basement membrane components was examined in the Passive Heymann Nephritis model of experimental membranous nephropathy. The extensive tissue injury that developed included subepithelial electron-dense deposits, podocyte foot process effacement, and expansion of the glomerular basement membrane. Levels of mRNA for type IV collagen, laminin, and fibronectin from isolated glomeruli was quantitated by slot-blot analysis and showed no change in experimental animals as compared to controls at either 1 week, 3 weeks, or 3 months after disease induction. Immunoelectron microscopy with gold-labeled anti-laminin IgG revealed no difference in the number of particles bound to the glomerular basement membrane of experimental animals and controls. Immunofluorescence with both type IV collagen antisera and anti-laminin antibody showed no difference in the intensity or pattern of staining. Despite extensive glomerular damage and glomerular basement membrane thickening, no evidence was found for either an increase in the synthetic rate of type IV collagen, laminin, or fibronectin or for an accumulation of basement membrane laminin within the damaged glomeruli. Alternate processes, such as diminished density of matrix components or accumulation of other unmeasured matrix constituents, presumably account for the expansion of the glomerular basement membrane seen in experimental membranous nephropathy. 相似文献