Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathic disorder. CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The pr...Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathic disorder. CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The present study carried out clinical classification according to clinical, electrophysiological and pathological features, conducted inheritance classification according to inheritance patterns, and performed mutation analysis of 13 CMT disease genes (PMP22, CX32, HSPB1, MNF2, MPZ, HSPB8, GDAP1, NFL, EGR2, SIMPLE, RAB7, LMNA, MTMR2) in 57 Chinese probands with CMT. Five cases of AD-CMT1 and 13 cases of sporadic CMT1 were diagnosed as CMT1A; five cases of X-CMT1, one case of X-CMT2 and one case of sporadic CMT1 were diagnosed as CMTXl; four cases of AD-CMT2 were diagnosed as CMT2F; one case of AD-CMT2 and one case of sporadic CMT2 were diagnosed as CMT2A2; one case of AD-CMT2 was diagnosed as CMT2L; one case of AD-CMT2 was diagnosed as CMT2J; one case of AR-CMT1 was diagnosed as CMT4A. Among the 57 CMT probands, seven genotypes were determined among 34 patients, with a detection rate of 59.6%. The results indicated that the clinical classification and inheritance classification are indispensable for selecting potential disease genes for mutation detection, and for efficient molecular diagnosis.展开更多
We previously found that the K141N mutation in heat shock protein B8 (HSPB8) was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a tr...We previously found that the K141N mutation in heat shock protein B8 (HSPB8) was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing K141N HSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis confirmed integration of the KI41NHSPB8 gene and widespread expression in tissues of the transgenic mice. The K141N HSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in K141N HSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings indicate that the KI4mHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease.展开更多
We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Toot...We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an 'onion-like' structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and 'mouse-nibbled'-Iike changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced.展开更多
This paper analyses the key issues and challenges of the smokescreen release optimal control under complex terrains and meteorological conditions, and proposes a dynamic model based theoretical framework that integrat...This paper analyses the key issues and challenges of the smokescreen release optimal control under complex terrains and meteorological conditions, and proposes a dynamic model based theoretical framework that integrates the smoke release equipments, the release time, the release positions, different ways to release smoke and launch attacks, various terrains and meteorological conditions and other factors so as to determine the appropriate smokescreen release plans through the rapid inverse for various threats and battlefield environments and to conduct realtime simulation and evaluation. This paper provides a theoretical basis for the smokescreen release optimal control.展开更多
基金the National Natural Science Foundation of China, No. 81071001, 30600200the Natural Science Foundation of Hu-nan Province, No. 2006JJ30009
文摘Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathic disorder. CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The present study carried out clinical classification according to clinical, electrophysiological and pathological features, conducted inheritance classification according to inheritance patterns, and performed mutation analysis of 13 CMT disease genes (PMP22, CX32, HSPB1, MNF2, MPZ, HSPB8, GDAP1, NFL, EGR2, SIMPLE, RAB7, LMNA, MTMR2) in 57 Chinese probands with CMT. Five cases of AD-CMT1 and 13 cases of sporadic CMT1 were diagnosed as CMT1A; five cases of X-CMT1, one case of X-CMT2 and one case of sporadic CMT1 were diagnosed as CMTXl; four cases of AD-CMT2 were diagnosed as CMT2F; one case of AD-CMT2 and one case of sporadic CMT2 were diagnosed as CMT2A2; one case of AD-CMT2 was diagnosed as CMT2L; one case of AD-CMT2 was diagnosed as CMT2J; one case of AR-CMT1 was diagnosed as CMT4A. Among the 57 CMT probands, seven genotypes were determined among 34 patients, with a detection rate of 59.6%. The results indicated that the clinical classification and inheritance classification are indispensable for selecting potential disease genes for mutation detection, and for efficient molecular diagnosis.
基金funded by the National Natural Science Foundation of China,No.81071001,30900805
文摘We previously found that the K141N mutation in heat shock protein B8 (HSPB8) was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing K141N HSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis confirmed integration of the KI41NHSPB8 gene and widespread expression in tissues of the transgenic mice. The K141N HSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in K141N HSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings indicate that the KI4mHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease.
基金funded by the National Natural Science Foundation of China, grant No. 81071001 and 30600200
文摘We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an 'onion-like' structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and 'mouse-nibbled'-Iike changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced.
文摘This paper analyses the key issues and challenges of the smokescreen release optimal control under complex terrains and meteorological conditions, and proposes a dynamic model based theoretical framework that integrates the smoke release equipments, the release time, the release positions, different ways to release smoke and launch attacks, various terrains and meteorological conditions and other factors so as to determine the appropriate smokescreen release plans through the rapid inverse for various threats and battlefield environments and to conduct realtime simulation and evaluation. This paper provides a theoretical basis for the smokescreen release optimal control.