A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

Chromosomal screening of mentally retarded school children in Taipei.

The major concern of the national population policy in Taiwan in recent years has been to lower the incidence of hereditary diseases and mental retardation in the general population. It has been estimated that there are around 10,000 mentally retarded school children in Taiwan. If effective chromosomal screening can be extended to these children, some of the family members who are carriers of balanced chromosomal rearrangements may benefit from follow-up studies and genetic counseling. The present report is the result of a pilot study conducted from 1988 to 1991 to explore the possibility of chromosomal screening of mentally retarded school children in Taipei. A total of 871 blood samples were collected from 1,147 children registered in 46 schools or residing in homes for the retarded. Chromosomal analysis was successfully accomplished on 674 out of 871 blood samples. The following chromosomal abnormalities were observed: 28 Down's syndrome, four Klinefelter syndrome, one XYY, one triple X, 11 translocations, seven inversions, four mosaics, three duplications, one deletion and one with an extra marker chromosome. After follow-up cytogenetic analyses of 13 families with probands with structural chromosomal anomalies, three of these families were shown to have one or two carriers of balanced translocated chromosomes. It seems that the present screening system would not be practical or cost-effective if it were applied island-wide in the future.     

PTEN抑癌基因在乳腺癌组织中的表达及其与乳腺癌微小转移灶的关系

目的:研究PTEN抑癌基因在乳腺癌组织中的表达,探讨其与乳腺癌病人的外周血、骨髓及前哨淋巴结微小转移灶之间的关系。方法:选择53例乳腺癌病人的组织标本,用免疫组织化学方法检测原发肿瘤PTEN蛋白的表达;用定量RT鄄PCR法测定原发肿瘤PTENmRNA的表达。以免疫细胞化学法检测外周血和骨髓中的微小转移灶;HE染色和免疫组织化学法检测前哨淋巴结中的微小转移灶。结果:外周血、骨髓及前哨淋巴结中微小转移灶的检出率分别是24.5%,56.6%,26.4%和41.5%。乳腺癌组织中PTEN蛋白表达呈丢失者占35.8%,后者与外周血和骨髓微小转移灶间无显著关系,而与前哨淋巴结中的微小转移密切相关(P≤0.001)。PTENmRNA的表达与外周血、骨髓及前哨淋巴结中的微小转移灶之间均无显著相关性。结论:乳腺癌组织中PTEN蛋白表达的丢失与前哨淋巴结中的微小转移有密切关系,可作为预测其早期转移的重要指标。     

Comparison of organic and inorganic germanium compounds in cellular radiosensitivity and preparation of germanium nanoparticles as a radiosensitizer

Purpose: The aim of this work is to compare the radiosensitizing effect between organic and inorganic germanium compounds and to investigate whether nanometer-sized germanium particles can act as radiosensitizers.

Materials and methods: Bis (2-carboxyethylgermanium) sesquioxide (Ge-132), germanium oxide (GeO₂) and germanium nanoparticles were used in this study. Cell viability was determined by clonogenic survival assay. Cellular DNA damage was evaluated by alkaline comet assay, confocal microscopy and the cellular level of phospho-histone H2AX (γ-H2AX).

Results: Nanometer-sized germanium particles were fabricated. They have a similar radiosensitizing effect as that of GeO₂. Conversely, Ge-132 did not enhance the radiosensitivity of cells. Comet assay was employed to evaluate the level of DNA damage and confirmed that inorganic germanium compounds enhanced cellular radiosensitivity. Notably, the comet assay indicated that the nanoparticle itself caused a higher level of DNA damage. The possibility that germanium nanoparticles per se caused DNA damage was ruled out when the cellular level of γ-H2AX was examined.

Conclusions: We demonstrated that inorganic but not organic germanium compounds exerted radiosensitizing effect in cells. Nanometer-sized germanium particles were fabricated and were able to enhance the radiosensitivity of cells. Confounding effect may occur when comet assay is used to estimate the level of DNA damage in the presence of germanium nanoparticles.     

经肛门内镜显微手术切除直肠肿瘤

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。     

Identification of a novel nonsense mutation in the rod domain of GFAP that is associated with Alexander disease

Alexander disease (AxD) is an astrogliopathy that primarily affects the white matter of the central nervous system (CNS). AxD is caused by mutations in a gene encoding GFAP (glial fibrillary acidic protein). The GFAP mutations in AxD have been reported to act in a gain-of-function manner partly because the identified mutations generate practically full-length GFAP. We found a novel nonsense mutation (c.1000 G>T, p.(Glu312Ter); also termed p.(E312*)) within a rod domain of GFAP in a 67-year-old Korean man with a history of memory impairment and leukoencephalopathy. This mutation, GFAP p.(E312*), removes part of the 2B rod domain and the whole tail domain from the GFAP. We characterized GFAP p.(E312*) using western blotting, in vitro assembly and sedimentation assay, and transient transfection of human adrenal cortex carcinoma SW13 (Vim⁺) cells with plasmids encoding GFAP p.(E312*). The GFAP p.(E312*) protein, either alone or in combination with wild-type GFAP, elicited self-aggregation. In addition, the assembled GFAP p.(E312*) aggregated into paracrystal-like structures, and GFAP p.(E312*) elicited more GFAP aggregation than wild-type GFAP in the human adrenal cortex carcinoma SW13 (Vim⁺) cells. Our findings are the first report, to the best of our knowledge, on this novel nonsense mutation of GFAP that is associated with AxD and paracrystal formation.     

Associations of the infancy body mass index peak with anthropometry and cardiometabolic risk in Mexican adolescents

Background: Early-life growth dynamics are associated with future health. Little is known regarding timing and magnitude of the infancy body mass index (BMI) peak with adiposity and metabolic biomarkers during adolescence.

Aim: To examine associations of the infancy BMI peak with anthropometry and cardiometabolic risk during peripuberty.

Methods: Among 163 ELEMENT participants, this study estimated age and magnitude of the infancy BMI peak from eight anthropometric measurements from birth–36?months using Newton’s Growth Models, an acceleration-based process model. Associations were examined of the infancy milestones with anthropometry and cardiometabolic risk at 8–14?years using linear regression models that accounted for maternal calcium supplementation and age; child’s birthweight, sex, and age; and the other infancy milestone.

Results: Median age at the infancy BMI peak was 9.6?months, and median peak BMI was 16.5?kg/m². Later age and larger magnitude of the peak predicted higher BMI z-score, waist circumference, and skinfold thicknesses; i.e. each 1?month of age at peak and each 1?kg/m² of peak BMI corresponded with 0.04 (0.01–0.07) and 0.33 (0.17–0.48) units of higher BMI z-score, respectively. Later age at peak was also a determinant of worse glycaemia and higher blood pressure.

Conclusion: Later age and larger magnitude of the infancy BMI peak are associated with higher adiposity at 8–14?years of age. Later age but not magnitude of the BMI peak are related to a worse cardiometabolic profile during peripuberty.     

Moderation of hemophilia A phenotype by the factor V R506Q mutation

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.