Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency

An infant girl with elevated blood lactate, pyruvate, and plasma branched-chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4) deficiency. Activities of the pyruvate dehydrogenase complex and E3 from patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in cultured skin fibroblasts, respectively. Western blot analysis demonstrated that the amount of E3 protein in fibroblasts from the patient and her father was about half of controls, while Northern blot analysis showed normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs from the patient revealed two mutations in separate alleles. One is a single base insertion of an extra adenine in the last codon of the leader peptide sequence (TAC-->TAAC) leading to a nonsense mutation which results in the premature termination of the precursor E3 polypeptide (Y35X). The other is a missense mutation due to substitution of guanine for adenine, causing an Arg-->Gly substitution at amino acid 460 of the mature protein (R460G) which triggers the loss of E3 activity probably by structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the parents demonstrated that the nonsense mutation was inherited from the father and the missense mutation was inherited from the mother.      

Biological resurfacing of the knee: a review of surgical management

Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee.     

Occurrence of paralytic shellfish poison (PSP) in the starfish Asterina pectinifera collected from the Kure Bay, Hiroshima Prefecture, Japan.

Assays were made for paralytic toxicity of marine invertebrates inhabiting at the coasts of Hiroshima Bay, where the infestation of bivalves such as cultured oysters with paralytic shellfish poison (PSP) has been occurred. The starfish Asterina pectinifera collected at the estuary of Nikoh River, Hiroshima Bay, was found to contain moderate levels of paralytic toxicity. Its highest toxicities as PSP found on July 30, 1999 were 12.5 MU/g for whole body, 11.0 MU/g for integument tissues and 3.9 MU/g for viscera, respectively. The toxicity of integument was changed from 3.6 to 11.0 MU/g in 1 year. Its paralytic toxin principles were identified as PSP toxins, composing mainly from saxitoxin (STX) group toxins such as carbamoyl-N-hydroxy neosaxitoxin (hyneoSTX), and STX, by HPLC and LC-MS, accounting for over 90 mol%. The PSP toxins contained in the starfish A. pectinifera considered to be transferred from bivalves or detritus living in the same area, which were contaminated with PSP. However, the involved pathway may be different from that of Asterias amurensis which was infested directly through food chain from its food bivalves, for its toxin pattern.     

Do the hamstrings and adductors contribute to excessive internal rotation of the hip in persons with cerebral palsy?

Children with cerebral palsy frequently walk with excessive internal rotation of the hip. Spastic medial hamstrings or adductors are presumed to contribute to the excessive internal rotation in some patients; however, the capacity of these muscles to produce internal rotation during walking in individuals with cerebral palsy has not been adequately investigated. The purpose of this study was to determine the hip rotation moment arms of the medial hamstrings and adductors in persons who walk with a crouched, internally-rotated gait. Highly accurate computer models of three subjects with cerebral palsy were created from magnetic resonance images. These subject-specific models were used in conjunction with joint kinematics obtained from gait analysis to calculate the rotational moment arms of the muscles at body positions corresponding to each subject’s internally-rotated gait. Analysis of the models revealed that the medial hamstrings, adductor brevis, and gracilis had negligible or external rotation moment arms throughout the gait cycle in all three subjects. The adductor longus had an internal rotation moment arm in two of the subjects, but the moment arm was small (<4 mm) in each case. These findings indicate that neither the medial hamstrings nor the adductor brevis, adductor longus, or gracilis are likely to be important contributors to excessive internal rotation of the hip. This suggests that these muscles should not be lengthened to treat excessive internal rotation of the hip and that other factors are more likely to cause internally-rotated gait in these patients.