Desensitization of mutant acetylcholine receptors in transgenic mice reduces the amplitude of neuromuscular synaptic currents

While the slow onset of desensitization of nicotinic acetylcholine receptors (AChRs), relative to the rate of acetylcholine removal, excludes this kinetic state from shaping synaptic responses in normal neuromuscular transmission, its role in neuromuscular disorders has not been examined. The slow-channel congenital myasthenic syndrome (SCCMS) is a disorder caused by point mutations in the AChR subunit-encoding genes leading to kinetically abnormal (slow) channels, reduced miniature endplate current amplitudes (MEPCs), and degeneration of the postsynaptic membrane. Because of this complicated picture of kinetic and structural change in the neuromuscular junction, it is difficult to assess the importance of the multiple factors that may be responsible for the reduced endplate current amplitudes, and ultimately the clinical syndrome. In order to address this we have used a transgenic mouse model for the SCCMS that has slow AChR ion channels and reduced endplate responsiveness in the absence of any of the degenerative changes. We found that the reduction in MEPC amplitudes in these mice could not be explained by either reduced AChR number or by reduced AChR channel conductance. Rather, we found that the mutant AChRs in situ manifested an activity-dependent reduction in sensitivity that caused diminished MEPC and endplate current amplitude with nerve stimulation. This observation demonstrates that the basis for the reduction in MEPC amplitudes in the SCCMS may be multifactorial. Moreover, these findings demonstrate that, under conditions that alter their rate of desensitization, the kinetic properties of nicotinic AChRs can control the strength of synaptic responses.     

The crystal structure of an Fe-superoxide dismutase from the hyperthermophile Aquifex pyrophilus at 1.9 A resolution: structural basis for thermostability

The incidence of stress fractures is increasing among competitive and recreational athletes as well as among children and the elderly. By understanding the continuum of bone's response to stress and maintaining an appropriate index of suspicion, the health care provider can diagnose these injuries appropriately. An accurate history and examination is essential and will differentiate stress fractures from other stress reactions. The more common stress fractures are discussed.     

The Childhood Injury Prevention and Promotion of Safety Programme (CHIPPS)

We report a case of cervical epidural hematoma associated with anticoagulant therapy in a 68 year-old man, who presented with tetraplegia. He was operated 12 hours after the onset. Three months later, he had recovered almost completely. The etiologies and prognosis of such lesions are reviewed.     

Detection of cytomegalovirus in semen from a population of men seeking infertility evaluation

This paper presents the results of in vivo measurements on a worker from a fuel reprocessing plant who was involved in an actinide intake. The results revealed that false indications of an actinide lung burden could arise from a contaminant present elsewhere in the chest region. Consequently, it is important that lung monitoring programs for occupational workers handling actinides are conducted with this caution in mind and that due consideration is given even in cases of minor cuts/wounds in order to rule out substantial overestimation of internal radiation doses.     

Tyrosine-dependent basolateral sorting signals are distinct from tyrosine-dependent internalization signals

Converting cysteine 543 to tyrosine in the influenza virus hemagglutinin (HA) introduces both a basolateral sorting signal and an internalization signal into the HA cytoplasmic domain. Another HA mutant, HA+8, contains eight additional amino acids at the end of the cytoplasmic domain that include a powerful internalization signal. HA+8 was also sorted efficiently to the basolateral surface of Madin-Darby canine kidney cells. The simplest explanation for the observation that multiple sorting phenotypes depend upon the same small amino acid sequence is that certain tyrosine-based internalization signals might also function as basolateral sorting signals. To test this hypothesis, second-site mutations were introduced into HA C543Y or HA+8 to determine if the internalization and basolateral sorting functions can be separated. For HA C543Y, the same sequence positions were important for both basolateral sorting and internalization, but the two functions responded differently to individual amino acid replacements, indicating that they were distinct. For HA+8, the basolateral sorting signal required the same tyrosine as the internalization signal, but did not share any other characteristics. Thus, even when basolateral sorting signals that depend on tyrosine overlap or are co-linear with internalizations signals, the two sorting processes are sensitive to different characteristics of the sequence.     

Multiple respiratory gas monitoring causes changes of inspired oxygen concentration in closed anesthesia system

This case report describes an accessory hepatic duct (AHD) identified by intraoperative cholangiography during excisional surgery of a choledochal cyst (CC). The accessory duct was divided and reconstructed successfully to the Roux-en-Y jejunal loop. The postoperative course was uneventful, and follow-up abdominal sonography revealed neither evidence of biliary tract obstruction nor atrophic changes of the liver. It is advocated that an AHD should be meticulously reconstructed if it is divided during excisional surgery of a CC.