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排序方式: 共有159条查询结果,搜索用时 46 毫秒
111.
Postnatal hemodynamic changes in very-low-birthweight infants. 总被引:3,自引:0,他引:3
T D Yanowitz A C Yao K D Pettigrew J C Werner W Oh B S Stonestreet 《Journal of applied physiology》1999,87(1):370-380
The purpose of this study was to characterize postnatal changes in regional Doppler blood flow velocity (BFV) and cardiac function of very-low-birthweight infants and to examine factors that might influence these hemodynamic changes. Mean and end-diastolic BFV of the middle cerebral and superior mesenteric arteries, cardiac output, stroke volume, and fractional shortening were measured in 20 infants birthweight 1,002 +/- 173 g, gestational age 28 +/- 2 wk) at 6, 30, and 54 h after birth and before and after feedings on days 7 and 14. Postnatal increases in cerebral BFV, mesenteric BFV, and cardiac output were observed that were not associated with changes in blood pressure, hematocrit, pH, arterial PCO(2), or oxygen saturation. The postnatal pattern of relative vascular resistance (RVR) differed between the cerebral and mesenteric vasculatures. RVR decreased in the middle cerebral but not the superior mesenteric artery. Physiological patency of the ductus arteriosus did not alter postnatal hemodynamic changes. In response to feeding, mesenteric BFV and stroke volume increased, and mesenteric RVR and heart rate decreased. Postprandial responses were not affected by postnatal age or the age at which feeding was initiated. However, the initiation of enteral nutrition before 3 days of life was associated with higher preprandial mesenteric BFV and lower mesenteric RVR than was later initiation of feeding. We conclude that in very-low-birthweight infants over the first week of life 1) systemic, cerebral, and mesenteric hemodynamics exhibit region-specific changes; 2) asymptomatic ductus arteriosus patency and early feedings do not significantly influence these postnatal hemodynamic changes; and 3) cardiac function adapts to increase local mesenteric BFV in response to feedings. 相似文献
112.
Previous investigations on the monkey kidney COS cell line demonstrated the
weak expression of fucosylated cell surface antigens and presence of
endogenous fucosyltransferase activities in cell extracts. RT-PCR analyses
have now revealed expression of five homologs of human fucosyltransferase
genes, FUT1, FUT4, FUT5, FUT7, and FUT8, in COS cell mRNA. The enzyme in
COS cell extracts acting on unsialylated Type 2 structures is closely
similar in its properties to the alpha1,3- fucosyltransferase encoded by
human FUT4 gene and does not resemble the product of the FUT5 gene.
Although FUT1 is expressed in the COS cell mRNA, it has not been possible
to demonstrate alpha1,2- fucosyltransferase activity in cell extracts but
the presence of Le(y) and blood-group A antigenic determinants on the cell
surface imply the formation of H-precursor structures at some stage. The
most strongly expressed fucosyltransferase in the COS cells is the
alpha1,6-enzyme transferring fucose to the innermost N -acetylglucosamine
unit in N - glycan chains; this enzyme is similar in its properties to the
product of the human FUT8 gene. The enzymes resembling the human FUT4 and
FUT8 gene products both had pH optima of 7.0 and were resistant to 10 mM
NEM. The incorporation of fucose into asialo-fetuin was optimal at 5.5 and
was inhibited by 10 mM NEM. This result initially suggested the presence of
a third fucosyltransferase expressed in the COS cells but we have now shown
that triantennary N- glycans with terminal nonreducing galactose units,
similar to those present in asialo-fetuin, are modified by a weak
endogenous beta-galactosidase in the COS cell extracts and thereby rendered
suitable substrates for the alpha1,6- fucosyltransferase.
相似文献
113.
M Kale R Ramsey-Goldman S Bernatsky MB Urowitz D Gladman PR Fortin M Petri E Yelin S Manzi S Edworthy O Nived S-C Bae D Isenberg A Rahman JG Hanly C Gordon S Jacobsen E Ginzler DJ Wallace GS Alarcón MA Dooley L Gottesman K Steinsson A Zoma J-L Senécal S Barr G Sturfelt L Dreyer L Criswell J Sibley JL Lee AE Clarke 《Arthritis research & therapy》2012,14(Z3):A15
114.
115.
116.
Ted D. Adams Robert C. Pendleton Michael B. Strong Ronette L. Kolotkin James M. Walker E. Sheldon Litwin Wael K. Berjaoui Michael J. LaMonte Tom V. Cloward Erick Avelar Theophilus E. Owan Robert T. Nuttall Richard E. Gress Ross D. Crosby Paul N. Hopkins Eliot A. Brinton Wayne D. Rosamond Gail A. Wiebke Frank G. Yanowitz Robert J. Farney R. Chad Halverson Steven C. Simper Sherman C. Smith Steven C. Hunt 《Obesity (Silver Spring, Md.)》2010,18(1):121-130
Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight‐loss intervention. Three groups of severely obese subjects (N = 1,156, BMI ≥ 35 kg/m2) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population‐based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes‐related variables, resting metabolic rate (RMR), sleep apnea, and health‐related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF‐36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux‐en‐Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight‐loss intervention was highly effective for weight loss, improved health‐related quality of life, and resolution of major obesity‐associated complications measured at 2 years. 相似文献
117.
118.
Selpi Christopher H Bryant Graham JL Kemp Janeli Sarv Erik Kristiansson Per Sunnerhagen 《BMC bioinformatics》2009,10(1):451
Background
Some upstream open reading frames (uORFs) regulate gene expression (i.e., they are functional) and can play key roles in keeping organisms healthy. However, how uORFs are involved in gene regulation is not yet fully understood. In order to get a complete view of how uORFs are involved in gene regulation, it is expected that a large number of experimentally verified functional uORFs are needed. Unfortunately, wet-experiments to verify that uORFs are functional are expensive. 相似文献119.
120.
Bruce E Vogel Cynthia Wagner Joanna Mathis Paterson Xuehong Xu Judith L Yanowitz 《Cell cycle (Georgetown, Tex.)》2011,10(12):1916-1920
Interactions between extracellular matrix (ECM) proteins and their transmembrane receptors mediate cytoskeletal reorganization and corresponding changes in cell shape during cell migration, adhesion, differentiation and polarization. Cytokinesis is the final step in cell division as cells employ a contractile ring composed of actin and myosin to partition one cell into two. Cells undergo dramatic changes in cell shape during the division process, creating new membrane and forming an extracellular invagination called the cleavage furrow. However, existing models of cytokinesis include no role for the ECM. In a recent paper, we demonstrate that depletion of a large secreted protein, hemicentin, results in membrane destabilization, cleavage furrow retraction and cytokinesis failure in C. elegans germ cells and in preimplantation mouse embryos.Here, we demonstrate that cytokinesis failure produces tetraploid intermediate cells with multipolar spindles, providing a potential explanation for the large number of aneuploid progeny observed among C. elegans hemicentin mutant hermaphrodites.Key words: aneuploidy, cytokinesis, extracellular matrix, C. elegans, cleavage furrow, hemicentin, tetraploid intermediateThe karyotype of C. elegans has five autosomes and one or two X chromosomes in males and hermaphrodites, respectively. The majority of self-progeny produced by wild-type hermaphrodites are hermaphrodites (∼99.8%), while rare meiotic nondisjunction of the X chromosome produces nullo-X gametes and 0.2% males. Mutations in over 30 genes result in a 10–150-fold increase in the frequency of males among hermaphrodite self-progeny, due to increases in defects in X chromosome segregation.1 The majority of these ‘him’ (high incidence of males) loci are genes that encode proteins associated with the intracellular machinery of meiotic chromosome segregation.2,3 Unique among him genes, the him-4 locus encodes hemicentin, a large, highly conserved component of the extracellular matrix (ECM).4 In addition to defects in germline chromosome segregation, him-4 mutants have pleiotropic defects in somatic cell adhesion and migration.1,4 The extracellular distribution of hemicentin at cell junctions that are defective in him-4 mutants dovetails with current models of cell adhesion and migration.5 However, it leaves unexplained several questions about how a secreted ECM component promotes correct chromosome segregation in the C. elegans germline.C. elegans hermaphrodite gonads are composed of two U-shaped tubes, and gametogenesis proceeds sequentially from the distal to the proximal end of each tube. Germ cells in C. elegans have incomplete cleavage furrows that connect them to a central cytoplasmic core, allowing distal cells to act as “nurses” while allowing more mature proximal oocytes to fill with bulk cytoplasm.6–8 Several genetic and cytogenetic observations suggest a mitotic rather than a meiotic origin for germline chromosome segregation defects observed in the absence of hemicentin.4 For example, jackpots of male progeny from individual hermaphrodites and nullisomy of primary meiocytes in him-4 mutants suggest a defect in a mitotic germline stem cell rather than in a post-mitotic process. Our recent work describing hemicentin localization at the cleavage furrows of dividing cells in the early mouse embryo and C. elegans germline, in addition to membrane destabilization, cleavage furrow retraction and cytokinesis failure in the absence of hemicentin, suggests that hemicentin has an evolutionarily conserved role in stabilizing and preventing retraction of nascent cleavage furrows.9Aneuploid cells are frequently observed in, and may be associated with the generation of, human tumor cells. Recent work from several laboratories suggests that cytokinesis failure is one of several mechanisms whereby tumor cells generate tetraploid intermediates that result in the production of aneuploid daughter cells in subsequent cell divisions. One proposed mechanism for the generation of aneuploid daughter cells from a tetraploid intermediate is thought to involve multipolar mitotic spindles that result in asymmetric mitoses.10–13To determine whether a similar mechanism might be responsible for the aneuploidy observed in the absence of hemicentin, him-4 (rh319) animals were examined for multipolar mitotic spindles. A significant fraction (14%) of mitotic germ cells have multipolar spindles that are not observed in a wild-type background (Fig. 1 and Fig. 1).Open in a separate windowFigure 1Multinucleate germ cells and multipolar germ cells observed in the mitotic zone of him-4 mutant hermaphrodites. (A) PH::RFP and histone::GFP in the mitotic region of wild-type (left) and him-4 (rh319) hermaphrodite gonads. Large numbers of multinucleate cells are observed among mitotic germ cells in mutant gonads (arrows). (B) PH::RFP and tubulin::GFP in the mitotic region of wild-type (left) and him-4 (rh319) hermaphrodite gonads. A significant fraction (14–16.
Open in a separate windowAlthough some genetic defects in the mitotic machinery produce a consistent syndrome of chromosome loss or gain, multipolar mitoses are predicted to result in a broad spectrum of chromosome sorting defects.13 To determine the types of chromosome sorting defects found in the absence of hemicentin, fluorescent in situ hybridization (FISH) was performed with a probe specific for the X chromosome and an autosomal probe specific for chromosome 5. Analysis of FISH experiments reveal a variety of abnormal karyotypes in germ cells throughout the gonad in him-4(rh319) mutant animals (Fig. 2). him-4 pachytene nuclei are generally larger than those found in wild-type animals and chromosome numbers are frequently elevated. Examination of oocytes in diakinesis indicates that the aneuploidy observed in him-4 mutant animals can affect all five autosomes in addition to the X chromosome and may include massive aneuploidy and more subtle “near-diploid” defects in chromosome number (either missing or supernumerary chromosomes) and complement (correct total number of chromosomes produced by absence of one chromosome and duplication of another chromosome, Fig. 2).Open in a separate windowFigure 2Meiotic defects in him-4 mutant germlines. FISH probes were used to mark the right end of the X chromosome (white) and the 5S locus on chromosome V (pink). DNA was stained with DAPI (blue). (A) Pachytene nuclei in wild type are evenly spaced and show one focus or 2 very closed foci for each chromosome, indicating that all chromosomes are properly paired and synapsed. (B) In him-4(rh319) mutants, pachytene nuclei are often larger than those found in wild-type animals and frequently have elevated chromosome numbers and the wrong complement of chromosomes. (C) Diakinesis nuclei in wild type show six spots corresponding to each of the six pairs of chromosomes, held together as chiasmata. In him-4, diakinesis defects reveal an array of chromosomal abnormalities: nuclei may have the correct number but the wrong complement of chromosomes (left), missing chromosomes (center, bottom) or supernumerary chromosomes (right). FISH XR, XL and 5S probes were synthesized and labeled as previously described in reference 17. FISH gonad preparation, fixation and hybridization of were performed according to published protocols.18 Scale bars = 5 µm.Our recent work showing that absence of hemicentin in the cleavage furrow can lead to cytokinesis failure in C. elegans germ cells and mouse embryonic cells undergoing cytokinesis,9 coupled with the observation of mitotic germ cells with multi-polar spindles (Fig. 1 and Fig. 2) suggest that the aneuploidy observed in him-4 mutant animals may arise by a mechanism similar to that described for the generation of aneuploid tumor cells.10–13We suggest a model where cytokinesis failure in the absence of hemicentin generates a tetraploid intermediate cell similar to those found in tumor cell precursors. These cells may have several distinct fates that include trisomies, tetrasomies and massive aneuploidy. Monosomy or nullisomy for chromosomes will occur when one or both homologs are not aligned on the metaphase axis, along which a subsequent cytokinesis occurs and will occur whether the subsequent cytokinesis is complete or incomplete along one axis (Fig. 3).10–13 The observation of large numbers of primary meiocytes with seven or more bivalent chromosomes suggests that partial cytokinesis does indeed occur in him-4 mutant animals.4 The generation of primary meiocytes with monosomy or nullisomy for the X chromosome can account for the large number of males among the offspring produced by him-4 mutant hermaphrodites, and autosomal aneuploidy is likely to account for the large numbers of inviable zygotes (∼40%).4Open in a separate windowFigure 3Model for the generation of monosomy in the germline of him-4 mutant animals. Absence of hemicentin in the cleavage furrow can lead to cytokinesis failure (1) and generation of a tetraploid intermediate cell. Centrosome clustering may result in a tripolar nuclear division that will produce trisomies, tetrasomies and massive aneuploidy and monosomy for chromosomes (blue), where one homolog (red) is not aligned on the metaphase axis along which cytokinesis occurs. Cells with monosomic chromosomes will be generated if the second cytokinesis is complete (2A) or incomplete along one axis (dotted pink line, 2B). (See refs. 10–13 for discussions of centrosome clustering and generation of tumor cell aneuploidy). 相似文献
Table 1
Severity and types of defective germ cells in him-4 gonadsDefect | Wild type | him-4 (rh319) |
Mitotic germ cells with multiple nuclei | 3/107 (3%) | 28/105 (27%) |
Mitotic germ cells with multipolar spindles | 0/108 (0%) | 16/115 (14%) |
Aneuploid pachytene germ cells | 6/524 (1%) | 257/741 (35%) |
Aneuploid diakinesis germ cells | 0/58 (0%) | 18/57 (32%) |