Anti-ganglioside (anti-GM1) antibodies have been implicated in the pathogenesis of Guillain-Barré syndrome, multifocal motor neuropathy and motor neuron diseases. It has been held that they may interfere with saltatory conduction by blocking sodium channels. We tested this hypothesis by analysing action potentials from 140 single nerve fibres in 22 rat ventral roots using external longitudinal current measurement. High-titre anti-GM1 sera from Guillain-Barré syndrome or multifocal motor neuropathy patients, or anti-GM1 rabbit sera were applied to the rat ventral root, where saltatory conduction in single motor fibres was serially observed for 4-12 h (mean 8.2 h). For control experiments, we also tested anti-galactocerebroside (anti-GalC) sera, which causes acute demyelinative conduction block, and tetrodotoxin (TTX), a sodium channel blocker. Conduction block was found in 82% of the fibres treated with anti-GalC sera and 100% treated with TTX, but only in 2% (one out of 44) treated with the patients' sera and 5% (two out of 38) treated with rabbit anti-GM1 sera. All the nodes blocked by anti-GM1 sera revealed intense passive outward membrane current, in the internode just beyond the last active node. This pattern of current flow was similar to that in fibres blocked by demyelination with anti-GalC sera, and quite different from that seen in fibres blocked by reducing sodium currents with TTX. Our findings suggest that anti-GM1 sera neither mediate conduction block nor block sodium channels on their own. We conclude that physiological action of the antibody alone is insufficient to explain clinically observed conduction block in human diseases.

Hyperostosis frontalis interna (HFI), symmetric thickening of the inner table of the frontal bone, is relatively common in women but very rare in men. We report the case of an elderly male patient with HFI. This patient was accompanied by primary hypogonadism, which may be related to the underlying pathogenesis of HFI.

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Widespread interspecific stimulation of antibiotic production occurs in strains of Streptomyces owing to the activity of diffusible substances, as previously determined in our investigations of the cross-feeding effect. In this study, we newly isolated a substance produced by a Streptomyces strain closely related to Streptomyces scabrisporus, based on the observation that this substance induced the production of an unknown antibiotic in another strain related to Streptomyces griseorubiginosus. This substance, named promomycin, is a polyether structurally related to lonomycin. Promomycin itself had an antibiotic activity, but it stimulated antibiotic production in multiple Streptomyces strains at sub-inhibitory concentrations. Evidence implies that this stimulation effect is widespread within this group of bacteria. The Journal of Antibiotics (2010) Keywords: antibiotic production; ionophore; polyether; promomycin; Streptomyces INTRODUCTION Antibiotic production in Streptomyces is affected by various environmental stimuli. 1 Accumulating evidence has shown that specific diffusible metabolites in addition to physicochemical stimuli induce antibiotic production in Streptomyces. Such metabolites include gbutyrolactone autoregulators, which are the best-characterized hormonal signals in Streptomyces and are widely distributed among members of this genus. Since the discovery of A-factor (2-isocapryloyl 3R-hydroxymethy-g-butyrolactone), secondary metabolism in Streptomyces has been shown to be generally controlled by this type of signal produced by the organism itself. 2 Both structural diversity and ligandreceptor specificity indicate that g-butyrolactone sensing occurs in an intraspecific manner, rather than in an interspecific manner.In contrast to the concept of autoregulation, our previous observations have shown that interspecific stimulation of secondary metabolism and/or morphogenesis takes place among various Streptomyces species and other related bacteria. 3 Cross-feeding assays on solid media (see Figure 1a as a reference) have shown that an array of colonies of one strain (corresponding to strain 574 in Figure 1a) responded to a concentration gradient of a substance diffusing from the colony of another strain (corresponding to strain 153 in Figure 1a). To determine whether such stimulatory events between different species involve unknown specific metabolites, we have attempted to isolate the metabolites responsible for the stimulatory activity. We recently identified desferrioxamines, which represent a

Immunocytochemical expression of tumor necrosis factor-alpha (TNF-alpha) was examined in nerve biopsy samples of patients with various disorders, focusing on nerve injury. TNF-alpha was mainly associated with phagocytosing macrophages in acute axonal injury, but the staining was more frequently seen in sections from patients with vasculitis than with metabolic neuropathy. Ramifield macrophages outside nerve fibers were also positive for TNF-alpha in the acute stage of vasculitis. In active demyelinating lesions from patients with chronic inflammatory demyelinating neuropathy (CIDP), macrophages outside nerve fibers showed weak staining with TNF-alpha, but the cells adhering to myelinated nerve fibers showed definite staining. This may be due, in part, to the smouldering course of CIDP, and expression may be up-regulated transiently during the demyelinating process. These results indicate that macrophages, as the effector cells for both axonal injury and active demyelination, express TNF-alpha, buth their activation mechanisms may vary among vasculitis, metabolic axonopathy and inflammatory demyelination.