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K12 is a high-prevalence antigen, with no known antithetical partner, that is associated with the Kell blood group system. We report studies on the 5th propositus (MS) with the K:-12 phenotype and the second case to show that the K12 is inherited. The anti-K12 in his serum did not destroy antigen-positive incompatible red cells transfused on at least 3 occasions over 6 years. Red cell membranes from MS possessed the Kell protein that was indistinguishable from control membranes. K12 antigen was shown by immunoprecipitation to be on a protein with an apparent molecular mass of 93,000 and by monoclonal antibody immobilization of erythrocyte antigens (MAIEA) assay to be on the Kell protein in proximity to K/k and Jsa /Jsb antigens. These data remove the K:-12 phenotype from its current Kell-related (or para Kell) status and elevates the K12 antigen to a bona fide member of the Kell blood group system. 相似文献
23.
Hereditary elliptocytosis (HE) is a heterogeneous disorder of red blood cells frequently associated with abnormal limited tryptic digestion of the alpha I domain of spectrin and impaired spectrin dimer self- association. We studied two related individuals with poikilocytic hereditary elliptocytosis (HE) of different severity. Limited tryptic digestion of spectrin from these individuals showed the presence of a variant alpha I/50b Kd peptide at the expense of the normal alpha I/80 Kd peptide. Amino acid sequence analysis of the abnormal peptide showed that the proteolytic cleavage occurred after the arginine at position 470 of the alpha spectrin chain. Spectrin from these patients had an impaired ability to undergo self-association, as evidenced by increased amounts of spectrin dimers in 4 degrees C extracts of erythrocyte membrane from affected individuals. The polymerase chain reaction was used to study the DNA sequence of the alpha spectrin gene encoding the region of the alpha spectrin chain surrounding the abnormal proteolytic cleavage site. We detected the in-frame deletion of the trinucleotide CAT, encoding histidine 469, two amino acid residues to the N-terminal side of the abnormal proteolytic cleavage site between residues 470 and 471. Similar to many other defects of spectrin associated with HE, this deletion occurs in helix three of repeat 5 of the proposed triple helical model of spectrin repeats. 相似文献
24.
Effect of growth hormone on body composition and visceral adiposity in middle-aged men with visceral obesity 总被引:1,自引:0,他引:1
Pasarica M Zachwieja JJ Dejonge L Redman S Smith SR 《The Journal of clinical endocrinology and metabolism》2007,92(11):4265-4270
RATIONALE: GH replacement in GH-deficient adults results in an improvement in metabolic status. GH might also decrease visceral adiposity in obese adults that are not GH deficient. OBJECTIVE: Our objective was to determine the effects of supraphysiological GH therapy on the metabolic syndrome and visceral adiposity in men with low blood levels of IGF-I and the durability of these effects after stopping GH therapy. DESIGN: The study was a double-blind, placebo-controlled 6-month intervention trial followed by a blinded follow-up period of 6 months. SUBJECTS: Thirty nondiabetic middle-aged men with central adiposity (body mass index > 27 kg/m(2); waist circumference > 102 cm) participated. RESULTS: After 6 months of GH therapy, we observed an increase in weight and lean body mass (2.5 +/- 0.6 kg, P < 0.05 compared with baseline and placebo) and 8.8% reduction in visceral adiposity. GH increased resting energy expenditure by 172.5 +/- 41.6 kcal/24 h after 6 months of therapy. Fasting insulin, glucose, and the quantitative insulin sensitivity check index for insulin resistance increased during GH therapy. The effects of GH on fatness and visceral adiposity disappeared shortly after GH withdrawal, but weight remained increased over baseline and when compared with the placebo group (P < 0.05). CONCLUSION: These data suggest that GH therapy is associated with small but statistically significant decreases in visceral adiposity and an increase in lean mass and body weight. In viscerally obese subjects, supraphysiological GH administration is not an effective treatment; however, additional studies are needed to evaluate the effects of low-dose, physiological GH treatment. 相似文献
25.
W.L. Marsh N.J. Marsh A. Moore W.A. Symmans C.L. Johnson and C.M. Redman 《Vox sanguinis》1981,40(6):403-411
Abstract. McLeod phenotype red cells of the Kell blood group system have acanthocytic morphology and reduced in vivo survival. The phenotype has an X-linked mode of inheritance and is found in some males who have no abnormality of leukocyte function and in some who have X-linked chronic granulomatous disease (CGD). We now describe an association between the McLeod phenotype and an abnormal elevation of serum creatine phosphokinase (CPK). The increase is of the MM isoenzyme type, derived from skeletal muscle or cardiac muscle, and muscle biopsy shows evidence of muscle cell changes. All of 11 males who have McLeod syndrome but do not have CGD have high levels of serum CPK. Males with McLeod syndrome and CGD may have normal or high levels of the enzyme. Individuals with other variant phenotypes in the Kell system have normal levels of serum CPK. Studies on a large kindred, which includes 5 people of McLeod phenotype, show high CPK levels only in the members of McLeod type. We conclude that the high level of CPK in the serum of these people is a reflection of a muscle cell anomaly and that in these individuals it is a pleiotropic effect of the X-linked gene that produces the McLeod red cell phenotype. 相似文献
26.
27.
Redman LM de Jonge L Fang X Gamlin B Recker D Greenway FL Smith SR Ravussin E 《The Journal of clinical endocrinology and metabolism》2007,92(2):527-531
OBJECTIVE: Our objective was to test the safety and metabolic effects of a novel beta(3)-adrenoreceptor agonist (TAK-677) in humans. DESIGN, SETTING, AND PARTICIPANTS: Sixty-five obese (body mass index = 33.9 +/- 2.1 kg/m2, mean +/- se) men and women (31.4 +/- 0.9 yr) participated in a double-blind placebo-controlled study at an institutional research center. INTERVENTION: Participants were randomized to 0.1 mg TAK-677 twice daily (BID) (n = 21), 0.5 mg TAK-677 BID (n = 22), or placebo BID (n = 22) for 29 d. OUTCOMES: Drug safety, 24-h respiratory quotient (RQ), 24-h energy expenditure (EE), body composition, fat distribution, and fasting plasma concentration of substrates and hormones were assessed. An acute-response study was also conducted. RESULTS: The drug was well tolerated by all participants; however, heart rate was elevated (9 +/- 2 beats per minute) with the 0.5-mg BID dose. After 28 d of treatment and when compared with placebo, there was no change in 24-h RQ with either 0.1-mg BID (P = 0.1) or 0.5-mg BID (P = 1.0) doses of TAK-677. However, TAK, 0.5 mg BID, resulted in a small increase in 24-h EE that was significantly different from placebo [change from baseline, 13 +/- 17 (0.5 mg BID) vs.-39 +/- 18 (placebo) kcal/d, P < 0.05]. Changes in weight, fat-free mass, and abdominal fat depots (visceral or sc) were not different between the three groups, nor were changes in fasting insulin, free fatty acid, or glucose concentrations. CONCLUSION: TAK-677 has no effect on 24-h RQ or fat oxidation but does slightly increase 24-h EE at the highest dose (0.5 mg BID). The acute studies showed large interindividual variability in plasma concentrations of TAK-677 indicating some possible problems with bioavailability and therefore efficacy. 相似文献
28.
CALLA-positive myeloma: an aggressive subtype with poor survival 总被引:5,自引:0,他引:5
Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group. 相似文献
29.
Two membrane proteins express the antigens that comprise the Kell blood group system. A single antigen, Kx, is carried on XK, a 440-amino acid protein that spans the membrane 10 times, and more than 20 antigens reside on Kell, a 93-kd, type II glycoprotein. XK and Kell are linked, close to the membrane surface, by a single disulfide bond between Kell cysteine 72 and XK cysteine 347. Although primarily expressed in erythroid tissues, Kell and XK are also present in many other tissues. The polymorphic forms of Kell are due to single base mutations that encode different amino acids. Some Kell antigens are highly immunogenic and may cause strong reactions if mismatched blood is transfused and severe fetal anemia in sensitized mothers. Antibodies to KEL1 may suppress erythropoiesis at the progenitor level, leading to fetal anemia. The cellular functions of Kell/XK are complex. Absence of XK, the McLeod phenotype, is associated with acanthocytic red blood cells (RBCs), and with late-onset forms of muscular dystrophy and nerve abnormalities. Kell, by homology, is a member of the neprilysin (M13) family of membrane zinc endopeptidases and it preferentially activates endothelin-3 by specific cleavage of the Trp21-Ile22 bond of big endothelin-3. 相似文献
30.
I. Cetin B. Huppertz G. Burton H. Cuckle R. Gonen O. Lapaire L. Mandia K. Nicolaides C. Redman P. Soothill K. Spencer B. Thilaganathan D. Williams H. Meiri 《Placenta》2011
The Pregenesys Consensus Meeting held in Cambridge on 13 July 2009 was organized by the Pregenesys Consortium to review and critically discuss current knowledge regarding early markers of preeclampsia, to identify priorities and opportunities for future research, to consider issues that may need to be addressed in future recommendations and to highlight key issues in cost effectiveness and national policies concerning prediction and early screening for the risk of developing preeclampsia.This report summarizes the outcome of the Consensus Meeting and draws attention to issues for further investigation with specific regard to single versus multiple markers, early versus late risk identification, and the long-term effects on both maternal and perinatal health and the need to include these in any future cost-benefit assessment. 相似文献