Preimplantation genetic diagnosis using combined strategies on a breast cancer patient with a novel genomic deletion in BRCA2

Purpose

To perform Preimplantation Genetic Diagnosis (PGD) on a paternal Brca2 unknown mutation carrier with early-onset breast cancer, whose paternal grandmother and mother had breast cancer at 60s.

Method

Elucidating the linkage via single sperm haplotyping on patient''s carrier brother, and identifying the genomic deletion via BLAST followed by PCR screening. PGD was subsequently conducted.

Result

The mutant allele was found by using 4 microsatellite and 2 intragenic SNP markers. Recombination was detected in 8 % of sperms. BLAST was utilized to locate putative hairpin structure(s), followed by PCR screening with seven sets of primers. A novel 2,596 bp deletion containing exon 15 ~ 16 was identified. Due to the severity of phenotype and the integrity of exon 11 encoding RAD51 binding domain, and the fact that the patient''s mother also had breast cancer at her 60s, we speculate a possible coexistence of maternal breast cancer risk allele(s). Embryo biopsy was performed on day 3. Unaffected morula and blastocyst were replaced on day 5, resulting in a singleton livebirth. A breast lump appeared in the patient after delivery without the presence of malignant cells.

Conclusion

Concerning the assisted reproductive option for breast cancer patients, the possibility of coexistence of multiple familial risk alleles and the significance of each mutation to the phenotype should be evaluated. To eliminate misdiagnosis resulting from recombination and/or allelic drop-out, both direct mutation detection and linkage analysis approaches may be necessary. BLAST is a very useful and cost-effective tool for identifying large genomic deletion.     

带有蛋白转导结构域的bcr/abl癌蛋白片段表达及其跨膜转运

0　引言　人类免疫缺陷病毒 (human immunodeficiencyvirus,HIV) - 1编码的反式激活蛋白 TAT具有独特的跨膜运转方式 ,而且有转导速度快 ,效率高的特点 ,被称为蛋白转导结构域 (protein transduction domain,PTD) [1 ,2 ] .本研究用PCR扩增了慢性粒细胞白血病慢粒 bcr/ abl融合蛋白的基因片段 ,在其 5′端融合 PTD结构域的编码区后在大肠杆菌中进行了表达 .表达产物经纯化后 ,加入培养的 HL 6 0细胞 ,表达的蛋白可直接进入细胞内 .这一结果为用外源蛋白负载(L oading)免疫细胞提供了新的途径 .1　材料和方法1.1　 DNA重组　人工合…     

Gender and age differences among youth, in utilization of mental health services in the year preceding suicide in taiwan

The primary objective of this study was to explore gender and age differences in the use of medical services during the year preceding suicide. Data were obtained from the mortality dataset of Department of Health and National Health Insurance Database. Included in the sample were 862 persons aged 12-24?years who committed suicide in Taiwan between 2001 and 2004. We compared the records of medical service utilization of adolescents (ages 12-18?years) with young adults (ages 19-24?years). Persons in both age groups contacted general practitioners more often than other types of medical providers in the year preceding suicide, with the exception of the month before suicide. Females made greater use of medical services than males in both age groups. Suicide prevention strategies should increase the emphasis in training non-psychiatric medical practitioners to identify and treat young persons at suicide risk.     

Absence of ongoing activity in fibres arising from proximal nerve ends regenerating into mesothelial chambers

Morphological studies have indicated that proximal nerve ends of transected rat sciatic nerves regenerating into preformed mesothelial chambers show a different organization as compared to neuromas developed in contact with a muscle fascia. We have studied the physiological properties of nerve fibres arising from these types of preparations with reference to ongoing activity, response to mechanical stimulation and noradrenaline sensitivity. The study included also fibres arising from ligated and encapsulated neuromas. Fibres with ongoing activity arising from the neuroma could be found from neuromas in contact with a muscle fascia and also from ligated and encapsulated neuromas. This ongoing activity was enhanced by mechanical stimulation and i.v. infusion of noradrenaline. In contrast, fibres arising from proximal nerve ends in mesothelial chambers did not show ongoing activity. These silent fibres responded dynamically to light mechanical stimulation. Noradrenaline did not induce ongoing activity in these fibres.     

Second trimester maternal serum hCG level in an Asian population: normal reference values by ultrasound dating

OBJECTIVE: To establish normative data of maternal serum chorionic gonadotropin (hCG) during the second trimester in an Asian population. METHODS: We measured the maternal serum hCG levels in 17,955 normal singleton pregnancies between 15 and 21 weeks of gestation. The gestation age was estimated by measurement of fetal biparietal distance (BPD) in all cases. Median values of hCG at various gestational weeks were calculated and the values of hCG were converted to multiple of median (MoM). The incidences of low MoM value and high MoM value were also calculated. RESULTS: The mean and median values of hCG were 57,153 mIU/ml and 50,120 mIU/ml, respectively, at 15 weeks of gestation and then decreased to 30,898 mIU/ml and 26,226 mIU/ml, respectively, at 21 weeks. We found 8.6% and 9.4% of normal singleton pregnancies have hCG MoM values >2.0 MoM and <0.5 MoM, respectively. CONCLUSIONS: Our report provides a normal reference data of second trimester maternal hCG levels by ultrasound dating in an Asian population.     

Diagnosing daytime bladder symptoms in children with nocturnal enuresis: A comparison of brief parental questionnaire with in‐depth,physician‐elicited,assessment

Aims: To assess the accuracy of brief parental questionnaire reporting of daytime bladder symptoms in children with nocturnal enuresis and compare with in‐depth reporting elicited by physician assessment, for diagnosing monosymptomatic and non‐monosymptomatic nocturnal enuresis. Methods: A cross‐sectional study of consecutive children attending an outpatient nocturnal enuresis clinic at a tertiary paediatric hospital participated in the study. Parents were asked to complete a questionnaire as part of routine assessment at their first visit which was compared with a detailed clinical assessment by the physician involving eliciting a thorough history from the parent and child. Results: Parents of 585 children participated in the study (mean age 9.2 years, range 5.0–17.5 years). Sixty percent of children were males. There was poor agreement between initial parental reporting and physician diagnosis of monosymptomatic and non‐monosymptomatic nocturnal enuresis (Kappa = 0.3, 95% confidence interval 0.21–0.37), mainly because parents underreport daytime incontinence and urgency compared with physician‐elicited information (43% vs. 69% and 66% vs. 87%, respectively). Conclusions: Parents underreport daytime symptoms by 20–25%. Reliance on a brief parental history without prompting by physicians for daytime symptoms for diagnosing type of nocturnal enuresis may be misleading and result in suboptimal management.     

Use of the Optomap with lid retraction and its sensitivity and specificity#

Background: Optomap uses the ultra‐wide field scanning laser ophthalmoscopy to provide retinal examination. It permits fundus examination without the use of a mydriatic, which is more comfortable for the patients. This paper determines the sensitivity and specificity of the Optomap for detecting retinal signs under non‐mydriatic conditions. Methods: Fifty‐four eyes identified with retinal/choroidal signs and eight normal eyes were recruited from 31 Hong Kong Chinese subjects. Photo‐documentation of fundal changes was obtained with the Optomap under non‐mydriatic conditions before a dilated fundus examination by a clinician using standard procedures. The eyelid was retracted using a cotton bud when necessary. Dilated fundus examinations were performed by another clinician using binocular indirect ophthalmoscopy and slitlamp biomicroscopy with a fundus lens. The Optomap images were evaluated by four other investigators under masked condition. The International Classification of Disease, Ninth Revision (ICD‐9‐CM) was adopted for recording retinal features. Screening results were compared with those obtained using the dilated fundus examination as the gold standard. Results: The cotton bud method for eyelid retraction showed an improvement in the area of retina that could be visualised. The sensitivity and specificity of the Optomap averaged 76.4 and 71.9 per cent, respectively. Some fundal signs were missed by all observers in the Optomap but not with the biomicroscope. These included white‐without‐pressure, lattice degeneration, paramacular drusen and pigmentary changes at central fundus. Conclusion: Optomap serves as a reliable screening tool for fundus examination especially because it covers a much wider area of the peripheral retina than other digital instruments for fundus photography.     

A profile of the online dissemination of national influenza surveillance data

Background  

Influenza surveillance systems provide important and timely information to health service providers on trends in the circulation of influenza virus and other upper respiratory tract infections. Online dissemination of surveillance data is useful for risk communication to health care professionals, the media and the general public. We reviewed national influenza surveillance websites from around the world to describe the main features of surveillance data dissemination.