鼠巨细胞病毒感染小鼠骨髓单个核细胞亚群的研究

本研究旨在探索鼠巨细胞病毒(MCMV)在小鼠骨髓单个核亚群细胞中的感染特性。采用免疫磁珠分选法(MACS)分选小鼠骨髓单个核亚群细胞,包括lin+细胞、lin-细胞、lin-CD117+和lin-CD117-细胞;用MCMV攻击分选的各组分细胞并以细胞因子和诱导剂诱导细胞分化,最后检测病毒核酸及相关蛋白。结果表明:在MCMV感染的lin+细胞中可检测到病毒DNA和立即早期基因的转录产物及其蛋白,而在感染的lin-细胞中则未检测到任何病毒产物。通过添加细胞因子GM-CSF、rhEPO或佛波酯,则可以在感染的lin-细胞中检测到MCMV的立即早期和早期基因转录产物以及蛋白表达。在lin-CD117+和lin-CD117-细胞中也未检测到病毒基因转录产物,但MCMV感染可抑制lin-CD117+造血干/祖细胞集落的形成以及下调其表面标志CD117抗原的表达。结论:MCMV可在小鼠骨髓单个核亚群细胞中潜伏感染;小鼠骨髓中具有原始干/祖细胞性质的细胞群对MCMV不易感,但MCMV感染可对这些细胞的功能产生抑制作用,可使细胞表面标志表达下调。     

Quantitative evaluation of ventricular dilatation using computed tomography in infants with congenital cytomegalovirus infection

Background

Infants with congenital cytomegalovirus infection (CCMVI) may develop brain abnormalities such as ventricular dilatation, which may potentially associate with sensorineural hearing loss. There is currently no recognized method for quantitative evaluation of ventricle size in infants with CCMVI. Our objectives were to establish a method for quantitative evaluation of ventricle size using computed tomography (CT) in infants with CCMVI, and determine a cut-off value associated with abnormal auditory brainstem response (ABR) early in life.

Design/Subjects

This study enrolled 19 infants with CCMVI and 21 non-infected newborn infants as a control group. Infants with CCMVI were divided into two subgroups according to ABR at the time of initial examination: normal ABR (11 infants) or abnormal ABR (8 infants). Ventricle size was assessed by calculating Evans’ index (EI) and lateral ventricle width/hemispheric width (LVW/HW) ratio on brain CT images, and was compared among groups. A cut-off ventricle size associated with abnormal ABR was determined.

Results

EI and LVW/HW ratio were significantly higher in the CCMVI with abnormal ABR group than the control and CCMVI with normal ABR groups. Cut-off values of 0.26 for EI and 0.28 for LVW/HW ratio had a sensitivity of 100% and 100%, respectively, and a specificity of 73% and 91%, respectively, for association with abnormal ABR.

Conclusions

We established a method for quantitative evaluation of ventricle size using EI and LVW/HW ratio on brain CT images in infants with CCMVI. LVW/HW ratio had a more association with abnormal ABR in the early postnatal period than EI.     

MELAS phenotype associated with m.3302A>G mutation in mitochondrial tRNA gene

The m.3302A>G mutation in the mitochondrial tRNA^Leu(UUR) gene has been identified in only 12 patients from 6 families, all manifesting adult-onset slowly progressive myopathy with minor central nervous system involvement. An 11-year-old boy presented with progressive proximal-dominant muscle weakness from age 7 years. At age 10, he developed recurrent stroke-like episodes. Mitochondrial myopathy, encephalopathy, lactic acidosis, plus stroke-like episodes (MELAS) was diagnosed by clinical symptoms and muscle biopsy findings. Mitochondrial gene analysis revealed a heteroplasmic m.3302A>G mutation. Histological examination showed strongly SDH reactive blood vessels (SSVs), not present in previous cases with myopathies due to the m.3302A>G mutation. These findings broaden the phenotypic spectrum of this mutation.     

Coxsackievirus B4 myocarditis and meningoencephalitis in newborn twins

Coxsackievirus B4 (CB4) is a picornavirus associated with a variety of human diseases, including neonatal meningoencephalitis, myocarditis and type 1 diabetes. We report the pathological findings in twin newborns who died during an acute infection. The twins were born 1 month premature but were well and neurologically intact at birth. After a week they developed acute lethal neonatal sepsis and seizures. Histopathology demonstrated meningoencephalitis and severe myocarditis, as well as pancreatitis, adrenal medullitis and nephritis. Abundant CB4 sequences were identified in nucleic acid extracted from the brain and heart. In situ hybridization with probes to CB4 demonstrated infection of neurons, myocardiocytes, endocrine pancreas and adrenal medulla. The distribution of infected cells and immune response is consistent with reported clinical symptomatology where systemic and neurological diseases are the result of CB4 infection of select target cells.