Hearing impairment as an early sign of alpha‐mannosidosis in children with a mild phenotype: Report of seven new cases

Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDE^R) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management.     

Prosthetic hip joint infection due to Campylobacter fetus.

A case of postoperative prosthetic hip joint infection due to Campylobacter fetus subsp. fetus is described. Difficulties in isolation and antimicrobial susceptibility testing of this organism are discussed.     

Normal aging decreases regional homogeneity of the motor areas in the resting state

Our knowledge about aging modulation of the central motor system remains sparse and contradictory. In the current study, we used functional MRI (fMRI) to study the aging influence on regional homogeneity of the motor-related brain areas in the resting state. We found that regional homogeneity in extensive motor regions, like the cingulate motor area, cerebellum, primary motor cortex, premotor area, supplementary motor area, thalamus, globus pallidus and putamen was significantly decreased in aged subjects. Our study indicates that normal aging process may disrupt the function of motor areas in the resting state, which may contribute to the declined motor ability in aged population.     

蛋白转导域介导BCR/ABL抗原对CML患者T细胞的活化作用

目的：研究蛋白转导域(PTD)介导的BCR／ABL抗原对慢性髓细胞白血病(CML)患者T细胞的特异性活化作用。方法：利用基因工程技术，将PTD基因与CML b3a2 bcr／abl基因融合并原核表达。将纯化的PTD—BCR／ABL融合蛋白与CML患者外周血单个核细胞(PBMC)体外共孵育，用流式细胞仪分别检测CD4^ 、CD8^ T细胞上活化抗原CD25的表达。结果：终浓度为100mg／L的PTD—BCR／ABL抗原体外刺激4d后，10例CML患者中，5例表现为CD8^ T细胞活化，2例表现为CD4^ T细胞活化，其中有1例CD8^ 和CD4^ T细胞同时活化；而作为对照的BCR／ABL抗原刺激组无一例表现为CD8^ 或CD4^ T细胞活化。结论：PTD能将外源性BCR／ABL抗原转导入抗原呈递细胞内，加工呈递后激活抗原特异性CD8^ 及CD4^ T细胞，为CML特异性CD8^ 、CD4^ T细胞的体外活化及细胞免疫治疗开辟一条新的途径。     

MERKEL CELL TUMOR COEXPRESSING CYTOKERATIN AND NEUROFILAMENT PROTEINS

Whorled filaments 10 nm in width were identified by anti-intermediate filaments antibodies in a Merkel cell tumor from a 52-year-old man. Immunohistochemlcal tests revealed that the tumor was stained with anti-keratin antibody and antibodies against the 68-kd and 200-kd subunits of neurofilament proteins but not antibody against the 150-kd subunlt. This is the first reported case of Merkel cell tumor expressing a 200-kd subunit of neurofilament proteins.     

Significant HLA-A02 allelic variation revealed in chinese and caucasian populations

HLA-A2 subtypes (A^*0201 - ^*0212) were determined by oligotyping in HLA-A2 positive samples from four populations (Han Chinese, Dai Chinese, Caucasoids from Germany and Turkish individuals from Kayseri)(see table).

Two different findings can be concluded from this study: 1) Significant HLA-A^*02 allelic variations found in four populations. A^*0207 is the predominant A^*02 allele in the Dai population and absent in the German Caucasian and the Turkish population. In contrast, A^*0201 is the most prevalent allele in the Caucasian, Turkish and Han Chinese group. We also found a high proportion of A^*0206 and A^*0207 in Han Chinese. 2) A strong association has been found between A^*0207 and HLA-B46 and DR9 in the Dai minority population. This haplotype is also found in Han Chinese. Three DNA samples from Turkish and one from the Dai population are presently being sequenced because the reaction pattern was out of the expected (Supported by SFB 217)     

膝关节动脉的血液供应

本文通过动脉灌注,对120侧不同年龄(新生儿至87岁)尸体的膝关节骨性部和软组织的血液供应分别进行了研究。新生儿的膝动脉在软骨内分布呈节段性,软骨骨化后,骨骺和髌骨的动脉间建立广泛的吻合。骺软骨板分隔膝关节的骨骺与干骺端。随骺板的闭合,两者间有血管互相交通。骺板的血液供应来自骺动脉、干骺动脉和滋养动脉终末的毛细血管袢以及骨膜动脉网的小支。髌骨的动脉分3组,发自髌前丛和髌周动脉环。滑膜和髌下脂垫的血管分布丰富。肌睫和韧带在骨的附着处缺乏血管。成人半月板外1/5有血管分布,内4/5无血管。本文对膝关节血管分布的临床意义作了简要讨论。     

可切削渗透陶瓷玻璃料对不同堆积密度氧化铝基体的渗透

探讨了可切削渗透陶瓷 (Infiltration of Machinable- infiltrated- ceramic,MIC)渗透玻璃在不同堆积密度氧化铝基体中的渗透情况及渗透后复合体的颜色表达。在 110 0℃保温 2 h,将玻璃渗透到不同堆积密度的氧化铝基体中 ,分别测得其渗透深度和颜色参数。扫描电镜观察玻璃—氧化铝复合体断面。玻璃渗透深度的平方与氧化铝堆积密度有直线负相关关系 ,最小渗透深度为 3.0 92 m m。复合体的颜色系数与氧化铝堆积密度无相关性。渗透复合体在断裂过程中可见 :裂纹偏转、晶体拔出和穿晶断裂。本实验证实 MIC渗透玻璃的渗透性能达到临床要求。渗透后的复合体颜色稳定 ,强度可靠     

Prevention of immune dysfunction and vitamin E loss by dehydroepiandrosterone and melatonin supplementation during murine retrovirus infection

Female C57BL/6 mice infected with the LP-BM5 leukaemia retrovirus developed murine acquired immune-deficiency syndrome (AIDS). Dehydroepiandrosterone (DHEA) and melatonin (MLT) modify immune dysfunction and prevent lipid peroxidation. We investigated whether DHEA and MLT could prevent immune dysfunction, excessive lipid peroxidation, and tissue vitamin E loss induced by retrovirus infection. Retrovirus infection inhibited the release of T helper 1 (Th1) cytokines, stimulated secretion of Th2 cytokines, increased hepatic lipid peroxidation, and induced vitamin E deficiency. Treatment with DHEA or MLT alone, as well as together, largely prevented the reduction of B- and T-cell proliferation as well as of Th1 cytokine secretion caused by retrovirus infection. Supplementation also suppressed the elevated production of Th2 cytokines stimulated by retrovirus infection. DHEA and MLT simultaneously reduced hepatic lipid peroxidation and prevented vitamin E loss. The use of DHEA plus MLT was more effective in preventing retrovirus-induced immune dysfunction than either DHEA or MLT alone. These results suggest that supplementation with DHEA and MLT may prevent cytokine dysregulation, lipid oxidation and tissue vitamin E loss induced by retrovirus infection. Similarly, hormone supplementation also modified immune function and increased tissue vitamin E levels in uninfected mice.