Dynamic structures of motor proteins myosin and kinesin, and switch protein troponin as detected by SDSL-ESR

We have studied biological nano-machines, motor and switch proteins operating as supramolecular complexes by electron spin resonance (ESR) and found key features of their molecular movements. In all the systems, the specific movements of elements or domains were detected and quite dynamic at nanometer scale. We have observed two broad but distinct orientations, separated by a 25 degrees axial rotation, of a spin label attached specifically to the light chain (LC) domain of myosin motor in the muscle fibers. The distribution became only narrower upon muscle activation. ESR spectrum from the spin label of the neck-linker of dimeric kinesin motor consisted of immobilized and mobilized components and did not exhibit nucleotide-dependent mobility change. The distance between two labels of kinesin dimer was also measured by spin dipole-dipole interaction, showing a broad distribution and a nucleotide-dependent change on the nanometer scale (>1.5 nm). These results suggest that two LC domains of myosin and two neck linkers of kinesin play a similar role for sliding movement using two conformations. The spin label of the skeletal (Tn)-I regulatory domain (TnIreg) showed a large mobility change by Ca2+ ion suggesting a Ca-induced switch movement of TnIreg. Spin dipole-dipole interaction showed that in reconstituted muscle fibers both skeletal and cardiac TnC undergo Ca2+-induced structural change that is thought to be essential for TnIreg movement. We also succeeded in fixing the newly-synthesized bifunctional spin label rigidly on the TnC molecule in solution, indicating that we can determine the precise coordinate of the spin principal axis of troponin on the oriented filament.     

Prediction of the ultimate performance of side-tunnel single-polarisation fibre

As the result of recent progress in polarisation-maintaining optical waveguiding schemes, a basic question now arises: which of stress-induced type or geometrical type approach will finally offer better characteristics? The letter discusses the ultimate performance of a side-tunnel fibre which offers the strongest polarisation-maintaining capability among various geometrical-type ones. The result indicates that, if the structure is optimised, a relative bandwidth of truly single-polarisation characteristics of 0.21 and a normalised birefringence of 0.0045 can be achieved for a relative core-cladding index difference of 0.01. These values are comparable to or higher than the best data reported so far with stress-type ones.     

Case of familial amyloid polyneuropathy discovered at the development of hematemesis

In a retrospective study we analyzed clinical features and their prognostic significance in 72 patients with onset of multiple sclerosis by the age of 21 years. In juvenile multiple sclerosis disease progression does not depend on age of onset, severity of neurologic involvement, or polysymptomatic or monosymptomatic involvement at presentation.     

Predominant expression of platelet-activating factor receptor in the rat brain microglia

Cellular localization of platelet-activating factor (PAF) receptor in the rat brain was determined by (1) in situ hybridization, (2) Northern blot analysis in primary cell cultures of neurons, microglia, astrocytes, and fibroblasts, and (3) Ca2+ imaging in hippocampal culture. In situ hybridization revealed that the PAF receptor mRNA is expressed intensely in microglia and moderately in neurons. Northern blot analysis revealed that PAF receptor mRNA is the most abundant in microglia. In primary hippocampal cultures, PAF elevated intracellular Ca2+ concentration in microglia and also in neurons, but to a lesser extent. These results suggest predominant presence of PAF receptor in microglia. Cultured microglia also expressed cPLA2 mRNA the most intensely. PAF-activated microglia released arachidonic acid in a Ca(2+)-dependent manner and without conversion to its derivatives. We propose that microglia as well as neurons contribute to PAF-related events in the CNS by releasing arachidonic acid.     

A case of macrophage activation syndrome developed with systemic juvenile rheumatoid arthritis

We reported a child of macrophage activation syndrome (MAS) associated with the course of systemic juvenile rheumatoid arthritis (sJRA). The clinical and laboratory findings in our case was ascribed to the overproduced inflammatory cytokines especially TNF-alpha by activated macrophages. Moreover, macrophage-colony stimulating factor (M-CSF) was also elevated in the active phase of the disease, and decreased in the convalescent phase, indicating that M-CSF can be the most potent stimulator of macrophages to produce inflammatory cytokines. Cyclosporine A along with plasmaexchange and corticosteroid, instead of VP16 or other immunosuppresive agents, was effecting in the management of this severe, life-threatening MAS.     

Effects of liposteroid on skin lesions in autoimmune MRLlpr/lpr mice

Urine leakage from the umbilicus was observed while expressing urine by the Crede manoeuvre in a three-year-old tetraplegic girl with a chronically distended urinary bladder. Intravenous urography (IVU) revealed bilateral hydroureteronephrosis with markedly distended urinary bladder. Regular three hourly intermittent catheterization was advised, and the parents and carers of this child agreed to perform catheterization. There was cessation of urine leak within 48 hours of urethral drainage. Cystography performed two weeks later showed no vesicoureteric reflux; vesicoumbilical fistula was no longer demonstrable. Follow-up IVU, performed after eight and half months of regular intermittent catheterization, showed regression of hydroureteronephrosis. We believe that urine leakage from the umbilicus served two important protective functions in this child, viz. (1) it prevented possible vesical or renal rupture; (2) the striking clinical symptom of urine leak from the umbilicus focussed the attention of the carers to the underlying serious condition of the urinary tract. Further, this case demonstrates that regression of marked hydroureteronephrosis can be achieved by intermittent catheterization performed at regular intervals by devoted parents/carers, in selected cases of spinal cord injury with neuropathic bladder, and vesical outlet obstruction, thus obviating the need for any form of temporary or permanent urinary diversion.