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11.
MacDonald I; Wang H; Grand R; Armitage RJ; Fanslow WC; Gregory CD; Gordon J 《Blood》1996,87(3):1147-1154
Group I Burkitt lymphoma (BL) cell lines, which retain the original biopsy phenotype, have been shown to enter apoptosis in response to a number of external stimuli including serum deprivation, thermal shock, addition of calcium ionophore, and ligation of surface immunoglobulin (Ig) by antibody. Transforming growth factor-beta 1 (TGF beta 1) is known to cause growth arrest in BL lines. Here we show that while it is by itself capable of promoting some degree of apoptosis in group IBL cells, TGF beta 1 cooperates with anti-immunoglobulin to this end. Trimeric soluble recombinant human CD40 ligand (sCD40L) was able to inhibit apoptosis induced by the combination of agonists to some degree, but such rescue proved to be short-lived. Both TGF beta 1 and anti-Ig individually caused BL cells to undergo growth arrest at the G1 phase of cell cycle before their entry into apoptosis: the consequence of sCD40L addition was to maintain the cells in cycle for longer. No induction of the apoptosis-protecting gene, bcl-2, occurred in the presence of sCD40L. These findings are discussed, particularly highlighting the relationship existing between survival and the cell cycle. The strong cooperative effects observed between anti-Ig and TGF beta 1 in promoting apoptosis and the inability of CD40 to signal for long-term rescue raise the potential for a novel therapeutic attack on B-cell lymphoma. 相似文献
12.
Moderation of hemophilia A phenotype by the factor V R506Q mutation 总被引:11,自引:1,他引:11
Nichols WC; Amano K; Cacheris PM; Figueiredo MS; Michaelides K; Schwaab R; Hoyer L; Kaufman RJ; Ginsburg D 《Blood》1996,88(4):1183-1187
Although many examples of unrelated hemophilia A patients carrying identical point mutations in the factor VIII (FVIII) gene have been reported, the clinical phenotype is not always the same among patients sharing the same molecular defect. Possible explanations for this discrepancy include undetected additional mutations in the FVIII gene or coinheritance of mutations at other genetic loci that modulate FVIII function. We report molecular genetic analysis of potential modifying genes in two sets of unrelated patients carrying common FVIII missense mutations but exhibiting different levels of clinical severity. Both mutations (FVIII R1689C and R2209Q) are associated with severe hemophilia A in some patients and mild/moderate disease in others. The common von Willebrand disease type 2N mutation (R91Q) was excluded as a modifying factor in these groups of patients. However, analysis of the recently described factor V (FV) R506Q mutation (leading to activated protein C resistance) identified a correlation of inheritance of this defect with reduced hemophilia A severity. Two moderately affected hemophilia A patients, each with either of two FVIII gene mutations, were heterozygous for FV R506Q, whereas two severely affected patients and two moderately affected patients were homozygous normal at the FV locus. Our results suggest that coinheritance of the FV R506Q mutation may be an important determinant of clinical phenotype in hemophilia A and that modification of the protein C pathway may offer a new strategy for the treatment of FVIII deficiency. 相似文献
13.
Arruda VR; Pieneman WC; Reitsma PH; Deutz-Terlouw PP; Annichino-Bizzacchi JM; Briet E; Costa FF 《Blood》1995,86(8):3015-3020
The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients. 相似文献
14.
经肛门内镜显微手术切除直肠肿瘤 总被引:14,自引:3,他引:14
目的评价经肛门内镜显微手术(TEM)切除直肠绒毛状腺瘤和早期直肠癌的应用效果。方法分析我院总结1995年11月至2001年12月27例TEM手术的临床资料。结果本组患者肿瘤直径中位值2.5cm,肿瘤下缘与齿状线距离(8.9±3.4)cm,肿瘤侵犯直肠周径范围(35.7±17.5)%。平均手术时间(109±46)min。平均住院日4.5d。无围手术期死亡。手术并发症有尿潴留、暂时性大便失禁和慢性阻塞性肺病(COPD)复发。术中2例切穿至腹腔,即刻内镜下修补成功。切缘100%瘤细胞阴性。病理示直肠绒毛状腺瘤14例、直肠腺癌13例,后者包括pTis2例,pT16例和pT25例。直肠癌腔内超声肿瘤T分期符合率为84.6%。5例pT2中2例中转前切除术,1例接受术后放疗,2例无附加任何治疗。平均随访18个月,所有病例无局部复发。死亡2例,但无复发迹象。结论TEM易行且安全,是直肠绒毛状腺瘤和部分T1直肠癌的治愈性手术,也可作为T2直肠癌的姑息性治疗手段。 相似文献
15.
Duncan WC; Illingworth PJ; Young FM; Fraser HM 《Human reproduction (Oxford, England)》1998,13(9):2532-2540
The molecular mechanisms involved in luteolysis are still unclear in the
primate. This study aimed to investigate the effect of induced luteolysis
on the ovarian luteinizing hormone (LH) receptor and the steroidogenic
enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset
monkey. Luteolysis was induced in the mid-luteal phase either directly by
systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal
using systemic gonadotrophin releasing hormone antagonist (GnRHant)
treatment. The LH receptor was studied by isotopic mRNA in-situ
hybridization and in-situ ligand binding and 3beta-HSD expression was
studied using isotopic mRNA in-situ hybridization and immunohistochemistry.
Induced luteolysis was associated with a reduction in the expression of LH
receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a
reduction in the LH receptor (P < 0.05) and 3beta-HSD protein
concentrations within 24 h. There were no differences in the findings
whether luteolysis was induced with PGF2alpha or GnRHant. This study shows
that disparate mechanisms to induce luteolysis in the primate result in an
identical rapid loss of the LH receptor and 3beta-HSD. In conclusion,
induced luteolysis leads to rapid loss of the steroidogenic pathway in
luteal cells.
相似文献
16.
M ODowd T Geoghegan PL Munk G McAuley WC Torreggiani 《Journal of Medical Imaging and Radiation Oncology》2006,50(4):386-388
Osseous haemophilic pseudotumours are uncommon. The commonest sites of involvement are the femur and the pelvis. Trauma is the initiating factor in most reported cases and repeated bleeding into the lesion contributes to their growth. Most lesions grow slowly and are often asymptomatic. Complications include massive haemorrhage, infection and pathological fracture. We present an extremely unusual presentation where a large haemophilic pseudotumour of the pelvis extended to impinge the adjacent colon, resulting in large bowel obstruction. 相似文献
17.
Objective : To evaluate the efficacy of biliary‐enteric bypass in the palliation of malignant hilar biliary obstruction. Materials and Methods : Records of 19 patients from 1995 to 1998 were reviewed. There were 13 patients with cholangiocarcinoma and 6 patients with carcinoma of the gallbladder. Single biliary‐enteric bypass had been performed in 13 of the patients; the rest had more than one biliary‐enteric anastomosis. Results : The 30‐day mortality was 21% (4/19 patients). Bile leakage occurred in 2 patients, leading, in both, to fatality. Excluding the 30‐day mortality, the median survival of patients with carcinoma of the gallbladder and cholangiocarcinoma was 116 days (43–200) and 202 days (47–1207), respectively. The mean hospital stay was 31 days (13–59) and all patients were discharged with their symptoms relieved and a drop in bilirubin of at least two‐thirds their pre‐operative level. The late complication rate was 26.7% (4/15 patients). Conclusion : Biliary‐enteric bypass is effective in the palliation of symptoms of patients suffering from unresectable hilar biliary obstruction, although it carries considerable mortality and morbidity. Stenting, rather than surgery, should be considered for patients with unresectable gallbladder cancer. 相似文献
18.
Background
There are multiple studies in different countries regarding the prevalence of vitamin D deficiency. These studies showed high prevalence of vitamin D deficiency in Asian countries. This study tries to elucidate the prevalence of vitamin D deficiency and its influencing factors in population of Tehran.Methods
1210 subjects 20–64 years old were randomly selected. 25 (OH) D serum levels were measured. Duration of exposure to sunlight, the type of clothing and level of calcium intake and BMI were quantified based on a questionnaire.Results
A high percentage of vitamin D deficiency was defined in the study population. Prevalence of severe, moderate and mild Vitamin D deficiency was 9.5%, 57.6% and 14.2% respectively. Vitamin D serum levels had no significant statistical relation with the duration of exposure to sunlight, kind of clothing and BMI. Calcium intake in the normal vitamin D group was significantly higher than the other groups (714.67 ± 330.8 mg/day vs 503.39 ± 303.1, 577.93 ± 304.9,595.84 ± 313.6). Vitamin D serum levels in young and middle aged females were significantly lower than the older group.Conclusions
Vitamin D deficiency has a high prevalence in Tehran. In order to avoid complications of vitamin D deficiency, supplemental dietary intake seems essential. 相似文献19.
Background
Although an effective measles vaccine has been available for almost 40 years, in 2000 there were about 30 million measles infections worldwide and 777,000 measles-related deaths. The history of smallpox suggests that achieving measles eradication depends on several factors; the biological characteristics of the organism; vaccine technology; surveillance and laboratory identification; effective delivery of vaccination programmes and international commitment to eradication. 相似文献20.