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631.
Factor IX Chicago-2 and prothrombin Madrid were purified from patients with hemophilia B and congenital dysprothrombinemia, respectively. Each protein displays defects in zymogen activation secondary to the failure to cleave one of the sessile bonds whose cleavage is necessary for full coagulant activity. These proteins were isolated by immunoaffinity chromatography using conformation-specific antibodies directed at either factor IX or prothrombin. Factor IX Chicago-2 is cleaved abnormally by factor XIa, yielding a pattern consistent with the failure to cleave the sessile bond between Arg 145 and Ala 146. Prothrombin Madrid is cleaved abnormally by factor Xa, yielding a pattern consistent with the failure to cleave the sessile bond between Arg 271 and Thr 272. Peptide mapping was performed on reduced and alkylated factor IX, factor IX Chicago-2, prothrombin, and prothrombin Madrid, and the hydrolysates were separated by high-performance liquid chromatography. The mutant peptide in factor IX Chicago-2 was identified by automated Edman degradation as residues 143 through 188 of factor IX, and had a histidine substituted for arginine at residue 145. The mutant peptide identified in prothrombin Madrid corresponds to residues 267 through 285 of prothrombin and has the substitution of cysteine for arginine at residue 271. These mutations, each occurring at arginines, are identical to those in factor IX Chapel Hill and prothrombin Barcelona. These results suggest that a limited repertoire of point mutations, many affecting arginine residues, may be responsible for hereditary defects of the vitamin K-dependent proteins in patients with normal antigen levels. 相似文献
632.
Naliato EC Violante AH Caldas D Farias ML Bussade I Lamounier Filho A Loureiro CR Fontes R Schrank Y Loures T Colao A 《Pituitary》2008,11(1):21-28
Objectives (1) to evaluate bone density in women with prolactinoma treated with dopamine agonists and healthy controls, using dual energy
x-ray absorptiometry (DXA), (2) to classify the results according to the current International Society for Clinical Densitometry
(ISCD) criteria, and (3) to correlate bone density with lean and fat masses, biochemical data and clinical aspects of prolactinomas.
Materials and methods A cross-sectional study was performed in two University referral centers. Forty-five premenopausal women with prolactinoma
were submitted to DXA and blood analysis (prolactin, estradiol, testosterone, SHBG, calcium, phosphorus, PTH, C-telopeptides
of type 1 collagen, and osteocalcin) by the time of their clinical evaluation. They were compared with 25 control women of
similar age and body mass index distribution.
Results Women with prolactinoma had lower lumbar spine Z-score than controls. Femoral neck, trochanter, and total proximal femur Z-scores were similar in patients and controls. Twenty-two percent of the patients had Z-scores below the expected age range vs. 4% in the control group. Lumbar spine, femoral neck, and total proximal femur Z-scores were mainly correlated with the amenorrhea duration. The trochanter Z-score was associated with the gynoid lean/fat mass ratio.
Conclusions Based on the current ISCD criteria, bone density evaluation in women with prolactinoma reveals bone loss, especially of trabecular
type. Bone density in these patients was particularly associated with the duration of amenorrhea, which reinforces the importance
of the adequate disease control in women with prolactinoma in order to avoid complications of this disease. 相似文献
633.
The mechanism by which influenza virus interferes with polymorphonuclear leukocyte (PMN) chemotaxis was investigated. Incubation of human PMN with influenza A virus in vitro for 30 minutes significantly decreased PMN migration under agarose in response to N- formyl-methionyl-leucyl-phenylalanine (FMLP) or zymosan-activated serum. Virus-treated PMN tended to aggregate in the under-agarose assay. Aggregation was avoided by using a more dilute PMN suspension in filter assays. Virus treatment significantly decreased migration through 100-micron thick cellulose nitrate filters but had no effect on migration through 10-micron thick polycarbonate filters or on PMN bipolar shape change. Virus was not chemotactic in the polycarbonate filter assay and did not induce shape change in purified PMN. It was concluded that influenza virus did not interfere with the ability of PMN to recognize a chemoattractant, undergo shape change, and move a short distance but did limit the extent of migration. Inhibition could not be explained by chemotactic deactivation, since the virus was not chemotactic. 相似文献
634.
A distinct profile of six soluble adhesion molecules (ICAM-1, ICAM-3, VCAM-1, E-selectin, L-selectin and P-selectin) in rheumatoid arthritis 总被引:10,自引:1,他引:10
Littler AJ; Buckley CD; Wordsworth P; Collins I; Martinson J; Simmons DL 《Rheumatology (Oxford, England)》1997,36(2):164-169
Soluble forms of ICAM-1, VCAM-1, E-selectin, L-selectin, P-selectin and,
more recently, ICAM-3 are known to exist in human serum and have elevated
levels in numerous diseases. Previous studies have demonstrated that in
rheumatoid arthritis (RA) the levels of circulating sICAM-1 and sE-selectin
are elevated relative to healthy controls. We have compared the serum
profiles of these six soluble adhesion molecules in patients with RA (n =
22) to those seen in healthy controls (n = 10) using sandwich ELISA. In the
patients, there were significant elevations of serum sICAM-1 (P <
0.0001), sICAM-3 (P = 0.0327), sVCAM-1 (P = 0.0025), sL-selectin (P =
0.0194) and sP-selectin (P = 0.0025), but not E-selectin (P = 0.0672).
However, only sP- selectin was found to correlate with disease activity in
the patients (r = 0.461, P < 0.05). Thus, there is a distinct profile of
soluble adhesion molecules in RA of which only sP-selectin correlates with
disease activity.
相似文献
635.
JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor 总被引:5,自引:1,他引:5
Weiler SR; Mou S; DeBerry CS; Keller JR; Ruscetti FW; Ferris DK; Longo DL; Linnekin D 《Blood》1996,87(9):3688-3693
Stem cell factor (SCF) is a hematopoietic growth factor that interacts with the receptor tyrosine kinase, c-kit. We have found that SCF- stimulates rapid and transient tyrosine phosphorylation of JAK2 in human and murine cell lines, as well as in normal human progenitor cells. JAK2 and c-kit were associated in unstimulated cells with further recruitment of JAK2 to the c-kit receptor complex after SCF stimulation. Treatment of cells with JAK2 antisense oligonucleotides resulted in a 46% decrease in SCF-induced proliferation. These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway. 相似文献
636.
VY Kong GV Oosthuizen DL Clarke 《Annals of the Royal College of Surgeons of England》2015,97(4):269-273
Introduction
The spectrum of injury associated with anterior abdominal stab wounds (SWs) is well established. The literature on the spectrum of organ injury associated with SWs to the posterior abdomen, however, is limited.Methods
We reviewed our experience of 105 consecutive patients who had established indications for laparotomy managed over a 4-year period in a high volume trauma service in South Africa.Results
Of the 105 patients, 97 (92%) were male and the overall mean age was 24 years. Fifty-seven patients (54%) had immediate indications for laparotomy. The remaining 48 patients (46%) initially underwent active clinical observation and the indications for laparotomy became apparent during the observation period. Of the 105 laparotomies performed, 94 (90%) were positive and 11 (10%) were negative. Of the 94 positive laparotomies, 92 were therapeutic and 2 were non-therapeutic. A total of 176 organ injuries were identified: 50 (53%) of the 94 patients sustained a single organ injury while the remaining 44 (47%) sustained multiple organ injuries. The most commonly injured organs were the colon (n=63), spleen (n=21) and kidney (n=19).Conclusions
The pattern of intra-abdominal injuries secondary to SWs to the posterior abdomen is different to that seen with the anterior abdomen. Colonic injury is most commonly encountered, followed by injuries to the spleen and kidney. Clinicians must remain vigilant because of the potential for occult injuries. 相似文献637.
目的:探讨药师如何对重症肌无力患者提供个体化药学服务。方法:临床药师与临床医师密切配合,通过药物基因检测、审查药物相互作用、跟踪治疗药物监测结果、进行患者用药教育等方式,提供药学服务。结果:患者治疗方案调整后,实验室检查无明显异常,他克莫司血药浓度达到正常范围,病情有所改善。结论:临床药师加入临床治疗团队,提供个体化药学服务可以提高临床药物治疗效果。 相似文献
638.
Whang-Peng J; Knutsen T; Jaffe ES; Steinberg SM; Raffeld M; Zhao WP; Duffey P; Condron K; Yano T; Longo DL 《Blood》1995,85(1):203-216
Few reports correlating specific cytogenetic abnormalities with distinct subtypes of lymphoma have performed serial studies at diagnosis and at tumor recurrence or progression. In our file of 325 cytogenetically analyzed non-Hodgkin's lymphoma (NHL) patients studied over the past decade, 43 had serial biopsies, 39 of whom had at least two successful preparations; of the 43, nine had one and 32 had two or more cytogenetically abnormal specimens. In this study, we correlated cytogenetic, histopathologic, molecular, and clinical parameters. Patients with low-grade lymphomas were as likely as patients with intermediate- or high-grade lymphomas to acquire new chromosomal abnormalities with time (16 of 23 patients as compared with 7 of 16; P2 = .11, chi 2 test). In four patients, originally diagnosed indolent disease progressed to aggressive disease; all had t(14;18), all gained additional chromosomal abnormalities with disease progression, and three of the four expressed abnormalities associated with disease progression and/or short survival: der(18), +7, and/or +12. Cytogenetic results from early disease were compared with those obtained later in disease: in the t(14;18) group, the most common abnormalities were +7 (eight patients) and der(18) (five patients), both seen later in disease. The most common abnormalities in patients without t(14;18) were 6q deletions; they were seen in both early and late disease and were associated with significantly shorter survivals (P2 = .0014) compared with all patients without 6q deletions. Secondary chromosomal abnormalities, observed after at least one previous abnormal study, were seen in 19 of 22 t(14;18) patients and in 11 of 21 patients without t(14;18) and were associated with a poor survival (P2 = .13) compared with patients without any secondary chromosomal abnormalities. Chromosome 1 abnormalities were seen in almost half of the patients and were observed in initial specimens and early in disease as well as late in disease and as secondary abnormalities; 1q involvement was more frequent than 1p (15 versus eight patients) and was significantly associated with poor survival only in patients with intermediate-/high- grade disease; the most common breakpoints were 1q21-q22 (nine patients) and 1p36 (six patients). Breakpoints at 2q21 and 3q27-q29 were limited to patients with t(14;18) and were almost exclusively secondary in nature. Molecular studies in 24 of our patients showed discrepancies with the cytogenetic results in only three patients: two had t(14;18) but no molecular rearrangements while two patients had no visible t(14;18) but were positive for major breakpoint region (MBR) rearrangement. The presence of MBR or minor breakpoint cluster (MCR) rearrangement had no apparent effect on survival.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
639.
Cytogenetics of childhood T-cell leukemia 总被引:6,自引:0,他引:6
Raimondi SC; Behm FG; Roberson PK; Pui CH; Rivera GK; Murphy SB; Williams DL 《Blood》1988,72(5):1560-1566
The karyotypes of 57 cases of childhood T-cell acute lymphoblastic leukemia (ALL) were analyzed to establish the cytogenetic profile in this disease. Three questions were of particular interest. Do the chromosomal changes in T-cell ALL preferentially affect bands where genes encoding the T-cell receptor for antigen (TCR) have been mapped? Do alterations involving the TCR gene regions appear with any notable frequency in B-progenitor ALL? Do chromosomal abnormalities in this disease relate to stage of T-cell ontogeny? A relatively high proportion of cases (65%) had a pseudodiploid karyotype at presentation, the majority (58%) characterized by a translocation. The overall frequency of translocations was 44%, comparable to that among all banded cases of ALL seen in our laboratory. Hypodiploidy and hyperdiploidy were exceedingly rare (only four of 57 cases); 16 cases (28%) had apparently normal karyotypes. In half the cases with a translocation (14 of 24), the breakpoints were in regions to which the alpha and beta chain TCR genes have been mapped. Chromosomal breakpoints that were consistently observed in the vicinity of TCR gene loci were 7q32-q36 (TCR beta chain; n = 8), 14q11-q13 (TCR alpha chain; n = 6); other frequent breakpoints were 9p13-pter (n = 8) and 6q15-qter (n = 9). Chromosomal alterations occurred near TCR gene loci significantly more often in T-cell cases than in a comparison group of 335 patients with B-cell precursor ALL (26% v 1.5%, P = .0001). Stage I thymocyte development (CD7+, CD2+, CD5+, CD1-, CD3-, CD4-, CD8-) was noted in 23 cases, stage II (CD7+, CD2+, CD5+, CD1+, CD3-, CD4 +/-, CD8 +/-) in 25 cases, and stage III (CD9+, CD2+, CD1-, CD5+, CD3+, and either CD4+ or CD8+) in nine cases. The only statistically significant associations between cytogenetic findings and T-cell ontogeny were a higher frequency of normal karyotypes in cases with stage I thymocytes, and of pseudodiploidy in stage II cases. There was no apparent relationship between particular translocations and level of thymocyte maturation. Our findings indicate that most children with T-cell ALL have pseudodiploid karyotypes, although a surprisingly high percentage lack demonstrable abnormal clones. Specific chromosomal changes do not appear to be related to discrete stages of T-cell ontogeny as defined in this study, but they occur preferentially in bands containing TCR genes. 相似文献
640.
Cytogenetic features and serum lactic dehydrogenase level predict a poor treatment outcome for children with pre-B-cell leukemia 总被引:2,自引:0,他引:2
Pui CH; Williams DL; Kalwinsky DK; Look AT; Melvin SL; Dodge RK; Rivera G; Murphy SB; Dahl GV 《Blood》1986,67(6):1688-1692
Leukemic cells from 89 (24%) of 369 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have a pre-B immunophenotype. By comparison with blasts having the common ALL phenotype, the pre-B cells were more likely to have a DNA index less than 1.16 (P = 0.02), a pseudodiploid karyotype (P less than 0.001), and a chromosomal translocation (P = 0.001). Increased serum lactic dehydrogenase levels (P = 0.001) were also characteristic of pre-B ALL; otherwise, the clinical and laboratory features of the two groups were similar. A nonrandom chromosomal translocation, t(1;19)(q23;p13.3), was identified in blast cells from 16 (23%) of the 70 patients with pre-B ALL and adequate chromosome banding studies; different translocations were found in 11 of the remaining patients. The presence of any chromosomal translocation in the pre-B group was significantly related to a higher leukocyte count, an increased level of serum lactic dehydrogenase, an increased percentage of S-phase cells, black race, and a blast cell DNA index less than 1.16. Four presenting features were found to confer an increased risk of treatment failure among pre-B patients: pseudodiploidy, chromosomal translocation, black race, and higher serum lactic dehydrogenase level. In a multivariate analysis, pseudodiploidy emerged as the strongest factor for predicting relapse in pre-B ALL. The frequent association of chromosomal abnormalities of known adverse prognostic significance and high serum lactic dehydrogenase levels with pre-B-cell ALL explains, at least in part, the poor treatment outcome reported for children with this subtype of leukemia. 相似文献