Microarray analysis of differentially expressed genes in mouse bone marrow tissues after ionizing radiation

PURPOSE: To identify differentially expressed genes in mouse bone marrow involved in radiation-induced injury. MATERIALS AND METHODS: Microarray analysis was used to identify the differentially expressed genes and other techniques, e.g., polymerase chain reaction (PCR), western-blotting and antisense were also used to validate the results. RESULTS: DNA microarray analysis demonstrated that the mRNA of 34 genes increased and 69 genes decreased in mouse bone marrow cells (BMC) from C57BL mice 6 h after a whole body dose of 6.5 Gy. These differentially expressed genes were involved in a number of processes including DNA replication/repair, proliferation/apoptosis, cell cycle control and RNA processing. In these experiments, a decline of the mammalian homolog Sir2a (an acronym for the silent mating type information regulation 2 homolog [SIRT1]) mRNA accompanied by an increase of P53 protein acetylation was observed in irradiated BMC. To determine whether the reduced SIRT1 is related to the higher acetylation status of P53 after irradiation, we designed and synthesized antisense oligonucleotides (AS) targeting human SIRT1 mRNA. Notably, AS transfection increased tumor protein 53 (P53) protein acetylation and bax-luciferase activity in human bone marrow stromal cell line (HS-5) after radiation. Furthermore, the AS transfer stimulated cell apoptosis in post-irradiation HS-5 cells. CONCLUSION: Ionizing radiation (IR) affects the expression of a series of genes including genes involved in G1/S transition and the P53 pathway. Among those, reduction of SIRT1 was seen to be involved in transactivation of P53.     

The health-related quality of life of children with an extremity fracture: a one-year follow-up study

PURPOSE: To document the health-related quality of life (HRQOL) of children with an extremity fracture at 3 and 12 months postinjury and to determine whether it varies significantly by fracture region and site. METHODS: Children hospitalized for an extremity fracture at 4 pediatric trauma centers were studied. A baseline, 3-month, and 12-month telephone interview were completed by a primary caregiver to measure the child's HRQOL using the Pediatric Quality of Life Inventory (PedsQL). HRQOL was modeled as a function of injury, patient, and family characteristics using a longitudinal regression model. RESULT: Of the 100 children enrolled, 52 sustained a lower extremity fracture (LEF) and 48 an upper extremity fracture (UEF). Postinjury HRQOL scores were significantly poorer than preinjury scores for all subjects (P = 0.05). In addition, a significant proportion of subjects reported impaired physical and psychosocial HRQOL at 3 (44% and 46%, respectively) and 12 months (23% and 33%, respectively) postinjury. At 3 months postinjury, children with an LEF had significantly poorer HRQOL outcomes compared to children with a UEF. By 12 months postinjury, the physical function of children with a tibia and/or fibula fracture remained significantly lower than children with a UEF (P < or = 0.05). CONCLUSIONS: Children hospitalized for an extremity fracture suffered dramatic declines in physical and psychosocial well-being during the first 3 months postinjury. By 1 year postinjury, most children recovered; however, children with a tibia and/or fibula fracture still reported significantly poorer physical functioning.     

Mutational analysis of K-ras and Ras protein expression in larynx squamous cell carcinoma

The ras gene family (H, K and N-ras) encodes the Ras protein, a GTPase-activating protein that regulates several signal transduction pathways including cellular proliferation and differentiation. Mutations in codons 12, 13 and 61 of the ras genes constitute one of the most frequent alterations in human cancer. In the Western Hemisphere, a low frequency of mutations in these genes has been observed in head and neck carcinomas; a higher frequency has been found in countries such as India and Taiwan. Increased protein expression is a relatively frequent event in larynx carcinomas. This study was aimed to evaluate the participation of the k-ras gene and Ras expression in 20 Mexican patients with larynx squamous carcinoma, 2 with dysplasia and 4 with normal mucosa. Samples (of 26 patients) were embedded in paraffin and immunohistochemical analysis was performed for the Ras protein, as well as amplification of the k-ras gene exon 1 (108 bp) by laser capture microdissection. Then, DNA extraction, PCR and sequencing were performed looking for possible mutation in codons 12 and 13. All patients with larynx carcinoma were men, median age 62 years. Eighty-five percent of the patients had risk factors such as smoking and/or alcohol consumption, 25% were in clinical stages I and II, and 75% in stages III and IV; 45% of the patients presented tumor recurrence or persistence. In this study, no mutations were found in codons 12 or 13 of the k-ras gene; however, protein expression was observed in 95% of the samples and a higher expression of the protein was associated with tumor recurrence or persistence, although this was not statistically significant. Unexpectedly, well-differentiated carcinomas and dysplasias presented an increase in protein expression. These results suggest that ras may be involved in early stages of larynx carcinogenesis and may be activated by other mechanisms different from mutations, such as epigenetic events.     

Mortality due to lung cancer in Mexico

The highest mortality due to cancer worldwide for both genders corresponds to lung cancer (1,179,000 deaths). In Mexico, the crude mortality rate due to lung cancer was of 5.01 per 10(5) inhabitants in 1979. The most important risk factor is smoking. The present study was aimed at analyzing the mortality due to lung cancer in Mexico, assessing data from each of the states constituting the Mexican Republic during the 1998-2004 period. Data were obtained from the National Institute of Statistics, Geography and Informatics (INEGI, for its initials in Spanish) corresponding to deaths due to lung cancer (1998-2004). We estimated the mean annual mortality rate (MAMR) for each of the 32 states of Mexico. We used the "World Population Standard". The MAMR was standardized according to age (ARS) direct method, and the standard error was determined by Poisson's approximation at a 95% confidence interval. To know the excess risk due to mortality, we calculated the standardized mortality ratios (SMRs) of ARS for each federal state, using the national rate as reference. In this period, 397,400 deaths due to malignant neoplasms were recorded, corresponding 45,578 (11.5%) to lung cancer; for men, 31,025 (68.1%) with MAMR of 8.9 and the respective ARS of 13.2 both x10(5) inhabitants. For women, results were 4553 (31.9%) deaths with MAMR of 4.1 and ARS of 5.4 both x10(5) inhabitants. The highest mortality rates due to lung cancer in both genders were observed in the north of Mexico, whereas for women this was observed in the central states. Although smoking is the main risk for lung cancer, there are other factors such as environmental pollution or exposure to toxicants that could be associated to this cancer. The years potentially lost due to lung cancer were 258,550 for men and 133,315 for women, with a total of 391,865 according to histopathology registry neoplasm malignant RHNM (1985-1995). Studies focused on the characterization and measurement of polluting agents would be a good start to determine the level of participation of air pollution in the development of lung cancer.     

45例儿童神经母细胞瘤预后因素分析

目的 分析影响儿童神经母细胞瘤（NB）的临床预后因素,期望通过综合性诊断治疗方案改善NB的预后。方法研究对象为1998年10月至2003年12月新诊断为NB患儿,根据年龄及分期分为高、中、低危3组,各组采用包括不同化疗强度的NB综合治疗方案。方案包括确切分期分组,Ⅲ、Ⅳ期患儿延迟或二次肿瘤根治术,不同强度的化疗方案和完成化疗后全顺维甲酸诱导分化治疗,高危组在化疗结束时接受自身造血干细胞移植（ASCT）。结果年龄6个月至11岁,共45例。I期9例,Ⅱ期1例,Ⅲ期8例,Ⅳ期26例,1Vs期1例。6例在≤2个疗程后好转中放弃治疗;39例按计划治疗,11例接受了ASCT。获得完全缓解（CR）31例（80％）,获得部分缓解（PR）8例（20％）。中位随访期21个月（14个月至64个月）;末次随访时CR24例（62％）,中位CR时间为22个月;带病生存病情稳定4例,总生存率（SR）72％。疾病进展、复发或已死亡11例（28％）。大于18个月、Ⅲ期及Ⅳ期明显影响预后,P分别为0．04、0．003。不同危险组预后不同,P为0．003。肿瘤原发于后腹膜,Ⅲ、Ⅳ期患儿手术未能完全切除肿瘤和未能接受ASCT者预后差,但未达统计学有效水平,P=0．092、0．55和0,60。结论NB综合整体治疗方案较为合理。年龄大于18个月、Ⅲ期及Ⅳ期为预后不良因素。肿瘤原发于后腹膜、手术未能完全切除肿瘤和未能接受ASCT预后差,但P未达统计学有效水平。     

Relationship between repeating tonsillitis and Berger's disease. Report of A case and review of the literature

Berger's disease, so called IgA nephropathy, is a mesangioproliferative glomerulonephritis characterized by recurrent episodes of gross hematuria in relation with ENT infections like tonsillitis. We report a clinical case which presented that association and make a review of the literature about the possible advantages of tonsillectomy on the evolutive course and prognosis of the nephropathy.     

国产全热解碳双叶瓣的动物实验

目的 :探讨人造瓣膜动物实验的方法 ,并对国产瓣的性能作动物体内评价。方法 :体外循环下行羊的二尖瓣替换术 ,先作预实验以确定实验方法 ,后作正式实验。用心导管和超声 ,并用多巴酚丁胺负荷法模拟运动条件 ,分别测定人造瓣的血流动力学参数 ;根据动物存活情况及有无血栓形成和血栓栓塞等评价其生物相容性。结果 :预实验 10只羊均死亡 ,主要与瓣环撕裂有关 ;正式实验 5只羊均存活。术中和术后 2 .5年用导管法测得平均跨瓣压差分别为 0 .69± 0 .2 3k Pa、0 .81± 0 .0 4k Pa;动物尸检未见血栓形成和血栓栓塞。结论 :瓣环撕裂是本组手术主要死亡原因 ,选择适当体重的动物和保留瓣叶的折叠缝补 ,及术后合理的呼吸支持等是实验的关键 ;该国产瓣在动物体内血流动力学和抗血栓性能优良