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991.
Nonrandom inactivation of the X chromosome in early lineage hematopoietic cells in carriers of Wiskott-Aldrich syndrome 总被引:5,自引:7,他引:5
The Wiskott-Aldrich syndrome (WAS) is an X-linked (Xp11.22) recessive immunodeficiency syndrome characterized by susceptibility to opportunistic and pyogenic infections, thrombocytopenia, and eczema. Previous studies of obligate carriers of WAS documented that nonrandom inactivation of the X chromosome carrying the defective gene is observed in all peripheral blood cells. The existence of both abnormal platelets and lymphocytes is consistent with a defect that affects early hematopoietic precursors. We isolated CD34+ hematopoietic progenitor cells collected from obligate carriers of WAS by apheresis and used polymerase chain reaction analysis of a polymorphic variable number of repeats (VNTR) within the X-linked androgen receptor to document nonrandom inactivation. These data show that nonrandom inactivation of the X-chromosome in WAS-obligate carriers occurs early during hematopoietic differentiation. 相似文献
992.
JB Haddow H Adwan SE Clark S Tayeh SS Antonowicz P Jayia DW Chicken T Wiggins R Davenport S Kaptanis M Fakhry CH Knowles AS Elmetwally E Geddoa MS Nair I Naeem S Adegbola LJ Muirhead 《Annals of the Royal College of Surgeons of England》2014,96(5):352-358
Introduction
The surgical Apgar score (SAS) can predict 30-day major complications or death after surgery. Studies have validated the score in different patient populations and suggest it should be used to objectively guide postoperative care. We aimed to see whether using the SAS in a decisive approach in a future randomised controlled trial (RCT) would be likely to demonstrate an effect on postoperative care and clinical outcome.Methods
A total of 143 adults undergoing general/vascular surgery in 9 National Health Service hospitals were recruited to a pilot single blinded RCT and the data for 139 of these were analysed. Participants were randomised to a control group with standard postoperative care or to an intervention group with care influenced (but not mandated) by the SAS (decisive approach). The notional primary outcome was 30-day major complications or death.Results
Incidence of major complications was similar in both groups (control: 20/69 [29%], intervention: 23/70 [33%], p=0.622). Immediate admissions to the critical care unit was higher in the intervention group, especially in the SAS 0–4 subgroup (4/6 vs 2/7) although this was not statistically significant (p=0.310). Validity was also confirmed in area under the curve (AUC) analysis (AUC: 0.77).Conclusions
This pilot study found that a future RCT to investigate the effect of using the SAS in a decisive approach may demonstrate a difference in postoperative care. However, significant changes to the design are needed if differences in clinical outcome are to be achieved reliably. These would include a wider array of postoperative interventions implemented using a quality improvement approach in a stepped wedge cluster design with blinded collection of outcome data. 相似文献993.
Manuel Ruiz‐Lopez Alberto Titos Ivan Gonzalez‐Poveda Joaquin Carrasco Jose Antonio Toval Santiago Mera Julio Santoyo 《International wound journal》2014,11(2):228-229
Colonic fistulas in an open wound are always a challenge for colorectal surgeons, and this report provides a technique for the appropriate management of these cases. We communicate the use of a negative pressure dressing therapy as part of the palliative care for a patient following the development of an enterocutaneous fistula. The use of this therapy allowed us to keep the patient clean and comfortable during the last few days of his life. 相似文献
994.
Purpose
Limited data exist regarding the safety and efficacy of bevacizumab in pediatric patients under the age of 4 years. Here, we report a large cohort of pediatric patients under 4 years of age treated with bevacizumab.Methods
The primary objective was to document adverse events with a possible relationship to bevacizumab. Patients (n = 16) were identified through retrospective chart review and harbored a variety of conditions (44 % central nervous system (CNS) tumors, 31 % vascular anomalies, 13 % neuroblastoma, 12 % other).Results
The median age was 34.3 months (range 4.9–47.3), including five patients <2 years of age. Patients received bevacizumab for a median duration of 6.2 months, alone or with chemotherapy, and a median dose of 9.25 mg/kg (range 7.0–11.8). Partial responses were seen in 19 % of patients, and clinical improvements were seen in 69 %. Adverse events known to be associated with bevacizumab occurred in 37 %. Outcomes observed in this population resemble those reported for bevacizumab in older pediatric patients. The overall pattern and frequency of adverse events observed was similar to those seen in reports of older pediatric patients with a variety of conditions. The highest level of efficacy observed was seen among patients with vascular malformations or with low-grade CNS tumors.Conclusions
Our results suggest that the use of bevacizumab is safe for the youngest children.995.
Monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells induced by the glutamine antagonist acivicin 总被引:1,自引:0,他引:1
Previously we showed that starvation of HL-60 promyelocytic leukemia cells for a single essential amino acid induced irreversible differentiation into more mature monocyte-like cells. Although not an essential amino acid, glutamine is important in the growth of normal and neoplastic cells. The glutamine analogue, alpha S,5S-alpha-amino-3- chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) inhibits several glutamine-utilizing enzymes and therefore depletes cells of certain metabolic end products. The current study was designed to examine in vitro the effects of acivicin on growth and differentiation of several established human myeloid leukemia cell lines, including the HL-60 cell line, and of freshly isolated cells from patients with acute nonlymphocytic leukemia (ANLL). Four-day culture of HL-60 cells with acivicin at concentrations of 0.1 to 10.0 micrograms/mL (0.56 to 56 nmol/L) decreased cell growth by 33% to 88% as compared with untreated control cells. Viability of cells was greater than 92% for untreated cells and 93% to 41% for acivicin-treated cells. Cells treated with acivicin differentiated along a monocytic pathway as shown by increased H2O2 production and alpha-naphthyl butyrate esterase (NSE) content. Differentiation was time and dose dependent, and was irreversible. Changes in H2O2 production and NSE content were partially abrogated by co-culture with 10 mmol/L exogenous cytidine and guanosine but not by co-culture with other nucleosides or glutamine. At these concentrations of acivicin, differentiation was associated with expression of the N- formyl-methyl-leucyl-phenylalanine-receptor (FMLP-R) on 8% to 29% of cells as compared with 8% for control cells. Acivicin potentiated the differentiating effects of interferon-gamma, tumor necrosis factor, dihydroxyvitamin D3, dimethylsulfoxide, and retinoic acid. Culture of cells from the U937 (monoblastic), K562 (erythroleukemia), and KG-1 (myeloblastic) cell lines resulted in decreased growth and viability, but not consistently in differentiation. Acivicin decreased survival of freshly isolated ANLL cells and increased their H2O2 production and NSE content. These results suggest that the glutamine analogue acivicin may be useful as a differentiating agent with antileukemia activity in patients with ANLL. 相似文献
996.
Involvement of catecholamines in the effect of fasting on hepatic endothelial lipase activity in the rat 总被引:2,自引:0,他引:2
J Peinado-Onsurbe C Soler X Galan B Poveda M Soley M Llobera I Ramírez 《Endocrinology》1991,129(5):2599-2606
The effect of fasting on hepatic endothelial lipase activity in the liver of adult rats was investigated. We found that, both in male and female rats, fasting produced a progressive decrease of the hepatic endothelial lipase activity. Upon refeeding, the activity returned to control values in 48 h. In isolated livers from fed male rats, a sharp peak of hepatic endothelial lipase activity appeared in the perfusate upon heparin addition. It accounted for 75% of the total activity (heparin-released + residual) of the tissue. Fasting (24 h) decreased the heparin-releasable activity, and this effect was responsible for most of the decrease found in whole tissue. We suggest that the effect might be due to a decreased synthesis and/or secretion of the enzyme by hepatocytes, since isolated hepatocytes from fasted rats, incubated at 37 C, released 65% less activity to the incubation medium than hepatocytes from fed rats. Adrenaline, but not insulin, glucagon, dexamethasone, epidermal growth factor, or T3, decreased the amount of hepatic endothelial lipase activity released by hepatocytes isolated from fed rats. The effect of adrenaline appears to be mediated by alpha 1-receptors since phenylephrine but not isoprenaline reproduced, and prazosin but not propranolol blocked, the effect of the catecholamine. In the presence of cycloheximide, adrenaline also decreased the amount of activity released. We suggest that, in our incubation conditions (up to 3 h), the hormone affects the posttranslational processing of the enzyme. In vivo administration of prazosin blocked the effect of both noradrenaline and fasting on hepatic endothelial lipase activity in whole liver. Those results suggest that catecholamines are involved in the decreased hepatic endothelial lipase activity found in the liver of fasted rats, and points out the role of these hormones in the acute modulation of an enzyme involved in reverse cholesterol transport. 相似文献
997.
Rosenblatt JD; Giorgi JV; Golde DW; Ezra JB; Wu A; Winberg CD; Glaspy J; Wachsman W; Chen IS 《Blood》1988,71(2):363-369
We previously reported isolation of human T-cell leukemia virus II (HTLV-II) from a second patient (N.R.A.) with atypical hairy cell leukemia. Follow-up analysis of the characteristics of the patient's HTLV-II infection over a 2-year period has revealed that the patient had two coexistant lymphoproliferative disorders. Oligoclonally integrated HTLV-II was detected in DNA extracted from the patient's peripheral blood mononuclear cells on separate occasions greater than 1 year apart, similar to integration of HTLV-I seen in adult T cell leukemia/lymphoma. Although integrated provirus was readily detected, no HTLV-II viral RNA expression was seen in fresh peripheral blood lymphoid cells. Although the patient's peripheral blood consistently contained a majority of atypical lymphoid cells with a T cell antigenic phenotype, he ultimately developed extensive pleural, hepatic and soft tissue infiltration with malignant Tac+, tartrate-resistant, acid phosphatase-positive (TRAP+) B cells of clonal origin. To further characterize the role of HTLV-II, the patient's peripheral blood mononuclear cells were fractionated into four enriched subpopulations at autopsy. Oligoclonally integrated HTLV-II was detected in DNA from a T cell-enriched fraction and a CD8+ T cell-enriched fraction, but not in a CD4+ T cell-enriched fraction, a non-T cell fraction, or in B cells obtained from the malignant pleural effusion. We conclude that the patient harbored two distinct lymphoproliferative disorders, a TRAP+, Tac+ B cell malignancy consistent with hairy cell leukemia that did not contain HTLV-II and a Tac-, CD8+ lymphoproliferative syndrome with oligoclonally integrated HTLV-II. 相似文献
998.
Rees DC; Duley J; Simmonds HA; Wonke B; Thein SL; Clegg JB; Weatherall DJ 《Blood》1996,88(7):2761-2767
A Bangladeshi family is described in which the genes for both hemoglobin E (Hb E) and pyrimidine 5' nucleotidase deficiency are segregating. An individual homozygous for both these conditions has a severe hemolytic anemia, whereas family members who are homozygous for Hb E are asymptomatic and those homozygous for pyrimidine 5' nucleotidase deficiency have the mild hemolytic anemia that is characteristic of this disorder. Globin-chain synthesis experiments have shown that the mechanism underlying the interaction between these two genotypes is a marked decrease in the stability of Hb E in pyrimidine 5' nucleotidase-deficient red blood cells (RBCs). It has also been found that in the enzyme-deficient RBCs in which Hb E is highly unstable, free alpha-chains, though not beta E-chains, acoumulate on the membrane. In view of the increasing evidence that the hemolysis associated with pyrimidine 5' nucleotidase deficiency results not only from an increase in the level of erythrocyte pyrimidines, but also from inhibition of the hexose monophosphate shunt activity in young erythrocytes, it is likely that the marked instability of Hb E in the enzyme-deficient cells results from oxidant damage acting on a mildly unstable Hb variant. These observations may have important implications for the better understanding of the pathophysiology of Hb E/beta-thalassemia, globally the commonest important form of thalassemia. 相似文献
999.
Sempere L Aparicio JR Jover R Casellas JA Poveda MJ Alonso G Pérez-Mateo M 《Gastroenterologia y hepatologia》2005,28(2):68-70
Linitis plastica of the rectum is an uncommon entity that is difficult to diagnose due to the lack of mucosal lesions on endoscopy, the low diagnostic yield of biopsy and non-specific findings of barium radiology and computerized tomography. Rectal endoscopic ultrasonography has had a radical impact on the differential diagnosis of stenosing lesions of the rectum, among them linitis plastica, allowing diagnosis of this lesion even in patients with negative results of biopsy. 相似文献
1000.
目的:在兔固定的膝关节内定期注入透明质酸钠,观察关节内外组织的变化。方法:实验于2003-10/2004-04在大连医科大学完成。实验分组:新西兰兔24只,随机分为透明质酸钠组、生理盐水组、单纯对照组,每组8只。实验干预:用树脂绷带将兔右膝关节固定于伸直位,膝关节注射部位开窗,左膝自由活动(自身对照侧)。透明质酸钠组膝关节腔内注入透明质酸钠0.1mL,生理盐水组注射同等剂量的生理盐水,单纯对照组不向关节内注射任何药物,每周1次,共5次。实验评估:5周后麻醉下处死动物,去除外固定,采用改良Clarke-Weeknesser关节伸屈范围检查标准测量右膝关节的活动范围;采用改良的Rydell-Balazes肉眼粘连评分标准评估膝关节内纤维粘连情况;光镜下观察股间肌、股直肌、髌内外侧支持带的纤维变性情况。结果:动物饲养过程中死亡4只,进入结果分析透明质酸钠组7只,生理盐水组6只,单纯对照组7只。①右膝关节的活动范围:透明质酸钠组大于生理盐水组和单纯对照组[(37.86±2.94)°,(15.67±2.23)°,(14.29±1.96)°,P<0.01]。②膝关节内纤维粘连评分:透明质酸钠组小于生理盐水组和单纯对照组(1.44±0.49,3.33±0.44,3.44±0.57,P<0.01)。③光镜下透明质酸钠组股间肌、股直肌的纤维变性较生理盐水组和单纯对照组减轻,髌内外侧支持带胶原纤维成分的变化也减轻。结论:在固定的兔膝关节内注射透明质酸钠不但可以明显抑制关节内的纤维性粘连;还可以抑制关节外股间肌、股直肌、髌内外侧支持带的组织变性。 相似文献