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81.
Sandberg H Almstedt A Brandt J Gray E Holmquist L Oswaldsson U Sebring S Mikaelsson M 《Thrombosis and haemostasis》2001,85(1):93-100
Recombinant factor VIII SQ (r-VIII SQ), ReFacto, is a recombinant factor VIII product similar to the smallest active factor VIII protein found in plasma-derived factor VIII (p-VIII) concentrates. The protein comprises two polypeptide chains of 80 and 90 kDa and lacks the major part of the heavily glycosylated B-domain i.e. amino acids Gln744 to Ser1637. r-VIII SQ retains six potential glycosylation sites for N-linked oligosaccharides at asparagine residues 41, 239, 582, 1685, 1810 and 2118. We describe a thorough comparison of the characteristics of r-VIII SQ with those of p-VIII. The primary and secondary structures of r-VIII SQ were in good agreement with that of B-domain-deleted p-VIII (p-VIII-LMW) as shown by SDS-PAGE, Western blotting with antifactor VIII antibodies, tryptic mapping, amino acid sequence analysis and circular dichroism spectroscopy. A few divergences also existed. Thus r-VIII SQ was shown to contain a small amount of the single chain primary translation product of 170 kDa and also the product specific sequence of 14 amino acids, the SQ-link, in the C-terminal end of the 90 kDa chain. It was shown that r-VIII SQ had a high specific activity of about 14,000 IU VIII:C/mg as determined by use of a chromogenic substrate assay. The r-VIII SQ protein was comparable to p-VIII forms with a retained B-domain, in terms of potency measured by a chromogenic substrate or a two-stage clotting assay, in interactions with thrombin, and with activated protein C (APC) in combination with Protein S. The ability of r-VIII SQ to participate as a cofactor in factor Xa generation in a mixture of factors IXa and X, phospholipid and calcium was in conformity with that of p-VIII. Furthermore r-VIII SQ had a good binding capacity for phospholipid vesicles and von Willebrand factor (vWF) as shown in gel filtration studies. The same kinetics in binding to von Willebrand factor was found for r-VIII SQ and p-VIII as determined by real-time biospecific interaction analysis (BIA) with use of the BIAcore instrument. The apparent association rate constant was 4 x 10(6) M(-1)s(-1). Two dissociation rate constants were found, 1 X 10(-2)s(-1) and 4 x 10(-4)s(-1). The results extend the present knowledge that the factor VIII B-domain is dispensable for the factor VIII cofactor function in hemostasis. 相似文献
82.
Rosenthal DI Catalano PJ Haller DG Landry JC Sigurdson ER Spitz FR Benson AB 《International journal of radiation oncology, biology, physics》2008,72(1):108-113
PURPOSE: Oxaliplatin is a platinum analog and radiosensitizer active in colorectal cancer. We performed a Phase I trial to test the safety and preliminary efficacy of adding oxaliplatin to standard preoperative chemoradiation therapy for rectal cancer. METHODS AND MATERIALS: Eligible patients had T3 to T4 rectal adenocarcinoma. Patients received standard-dose radiation (50.4 Gy for 5.5 weeks) with concurrent infused 5-fluorouracil (5-FU) at 200 mg/m2 per day, 7 days per week. Oxaliplatin was given three times at 14-day intervals at 55, 70, or 85 mg/m2 during the 5.5-week radiation period, before resection. Adjuvant therapy consisted of four cycles of 5-FU (500 mg/m2 per week) with leucovorin (500 mg/m2 per week) given every 6 weeks. The main goals were to identify the maximum tolerated dose of oxaliplatin and the dose-limiting toxicities when given with 5-FU and RT. Secondary goals were to determine resectability, pathologic response, sphincter preservation, and overall survival rates. RESULTS: Twenty-one patients were enrolled, 5 at the 55 mg/m2 oxaliplatin dose level, 5 at 70 mg/m2, and 11 at 85 mg/m2. All patients were able to complete the preoperative chemoradiation regimen with no dose adjustments. No dose-limiting toxicities or differences in the type or extent of toxicity were noted among the groups. Nineteen patients underwent surgery (three abdominopelvic resections and 16 low anterior resections), for an 84% sphincter preservation rate. The pathologic complete response rate was 26% (5 patients), and minimal microscopic residual tumor was found in 21% (4 additional patients). CONCLUSIONS: Oxaliplatin was well tolerated at 85 mg/m2 given every 2 weeks in combination with standard preoperative chemoradiation for rectal cancer. The rates of major pathologic response and sphincter preservation are promising. 相似文献
83.
Strand EB Zautra AJ Thoresen M Ødegård S Uhlig T Finset A 《Journal of psychosomatic research》2006,60(5):477-484
OBJECTIVE: The purpose of this study is to examine positive affect (PA) as a factor of resilience in the relationships between pain and negative affect (NA) in a sample of patients with rheumatoid arthritis. METHODS: Forty-three patients (30 women; mean age, 57 years) were interviewed weekly by telephone for 8 weeks. Multilevel modeling was applied to study the within-week relationships among the variables. RESULTS: There was a Pain x PA interaction effect on NA (beta=-0.05, P<.01) indicating a weaker relationship between pain and NA in weeks with more PA. Pain (beta=0.37, P<.002), interpersonal stress (beta=2.42, P<.001), depression (beta=0.26, P<.01), average perceived stress (beta=10.80, P<.001), and also weekly PA (beta=-0.1, P<.01) had a main effect upon NA. CONCLUSION: Positive affect is most influential in reducing NA during weeks of higher pain and may be a factor of resilience, helping patients experiencing pain fluctuations as less distressful than at lower levels of PA. 相似文献
84.
We used human serum protein fractions to evaluate the sensitivity and bias of three turbidimetric methods for determining concentrations of proteins. Each fraction (Cohn Fractions II, III, IV, and V) was assigned a protein concentration value that was determined by the biuret method, which we calibrated with purified monomer of human serum albumin. All three turbidimetric methods (those involving sulfosalicylic acid/sodium sulfate, trichloroacetic acid, and alkaline benzethonium chloride) gave acceptable results for Fraction V with crystallized human serum albumin as the reference material, but there was bias by each of the three methods for the three globulin fractions. The method involving alkaline benzethonium chloride with measurement at 450 nm had the best sensitivity within the range of linearity and the most consistent bias among the three globulin fractions. These results define the dilemma for valid calibration of these methods for total serum protein in cerebrospinal fluid and urine. 相似文献
85.
Assessment of magnesium status 总被引:2,自引:0,他引:2
R J Elin 《Clinical chemistry》1987,33(11):1965-1970
The adult human body contains approximately 24 g (1 mol) of magnesium--about half in bone and half in soft tissues. Only about 0.3% of the total body magnesium is present in serum, yet the majority of analytical data obtained is from this body fluid. Assessing the magnesium status of an individual is difficult, there being at present no simple, rapid, and accurate test to determine intracellular magnesium, but determination of total and free magnesium in tissues and physiological tests provide some information. Changes in magnesium status have been linked to cardiac arrhythmias, coronary heart disease, hypertension, and premenstrual syndrome. A better understanding of magnesium transport and of factors controlling magnesium metabolism is needed to elucidate the role of magnesium in disease processes. 相似文献
86.
87.
Christina Lindholm Britt Arrelöv Gunnar Nilsson Anna Löfgren Elin Hinas Ylva Skånér Anna Ekmer Kristina Alexanderson 《BMC public health》2010,10(1):752
Background
How physicians handle sickness-certification is essential in the sickness-absence process. Few studies have focused this task of physicians' daily work. Most previous studies have only included general practitioners. However, a previous study indicated that this is a common task also among other physicians. The aim of this study was to gain detailed knowledge about physicians' work with sickness-certification and of the problems they experience in this work. 相似文献88.
We evaluated the bone-forming potential of isogeneic bone marrow combined with antigen-extracted, autolyzed allogeneic bone matrix (AAA bone a.m. Urist). The purpose of the experiment was to evaluate bone-inducing materials for application in orthopaedic devices designed for fixation by bone ingrowth into a porous surface. The bone-forming materials were packed into tubes of porous fiber titanium and placed in the back musculature of rats for 12 or 25 days. At 12 days the combination of bone marrow and AAA bone had produced more bone than marrow only. At 25 days, however, there was no difference. The bone-inducing materials produced substantial amounts of new bone, and may become an adjuvant for achieving fixation by bone ingrowth. In particular, a combination of AAA bone and marrow might enhance fixation at a very early postoperative stage. 相似文献
89.
90.
Larsen Claus Harboe Elin Johansen Marianne Olesen Henning Peter 《Pharmaceutical research》1989,6(12):995-999
We have determined initial rates of naproxen formation from dextran-naproxen ester prodrugs incubated in homogenates of various segments of the pig GI tract. Drug liberation proceeded 15–17 times faster in cecum and colon homogenates than in aqueous pH 7.4 buffer or homogenates of the small intestine. The degree of conjugate substitution did not affect the liberation rates, whereas enhanced drug activation was observed with decreasing molecular size of the carrier dextran. During incubation in colon homogenates the average molecular weight of the dextran prodrugs decreased. The mechanism of drug activation from the prodrugs may therefore involve an initial depolymerization step of the dextran chains by dextranases secreted from bacteria in the pig colon. The generated small fragments then serve as substrates for esterases and other hydrolases. 相似文献