Axonal Guillain-Barré syndrome: carbohydrate mimicry and pathophysiology

Abstract   Acute motor axonal neuropathy (AMAN), an axonal subtype of Guillain-Barré syndrome (GBS), is characterized by pure motor involvement, frequent antecedent infection by Campylobacter jejuni , association with anti-GM1 or anti-GD1a immunoglobulin G (IgG) antibodies, and the electrophysiological features of axonal degeneration and reversible conduction block. Molecular mimicry exists between GM1 and GD1a gangliosides and lipooligosaccharides (LOSs) of C. jejuni isolates from AMAN. Sensitization of rabbits with GM1 or C. jejuni LOS induces anti-GM1 IgG antibodies and subsequent flaccid paralysis. Pathological changes seen in rabbit model peripheral nerves are identical to those in human AMAN. Immunohistochemistry of AMAN rabbits shows disruption of nodal sodium channel clusters and detachment of paranodal myelin terminal loops, similar to paranodal demyelination, which would significantly reduce the safety factor for impulse transmission and might be responsible for the rapidly reversible conduction block frequently present in human AMAN. C. jejuni sialyltransferase (Cst-II), which functions in the biosynthesis of ganglioside-like LOSs, determines the transferase activity. Strains with cst-II (Thr51) express GM1 and GD1a epitopes, whereas GBS patients infected with cst-II (Thr51) strains have anti-GM1 or anti-GD1a IgG antibodies. The cst-II gene is responsible for the development of GBS. Immunological, pathological, electrophysiological, and bacteriological studies have provided strong evidence of carbohydrate mimicry being a cause of AMAN and clarified the mechanisms of nerve conduction failure in AMAN.     

Diagnostic classification and demographic features in 283 patients with somatoform disorder

A total of 283 patients with somatoform disorder (SFD) seen in a psychiatry clinic were surveyed and their diagnostic subtypes, demographic features, and comorbidities, analyzed. The results indicate that: (i) SFD comprises 5.8% of first-visit outpatients; (ii) undifferentiated SFD (USFD) and SFD not otherwise specified (SFD-NOS) account for the majority of patients; (iii) there are 1.7-fold more women than men; (iv) age of onset is lower in patients with somatization disorder or body dysmorphic disorder and higher in patients with hypochondriasis or pain disorder; (v) the mean number of years of education was 11.2 years; and (vi) comorbid illness were seen in 24.8% of patients, and included mood disorder, anxiety disorder, and personality disorder, as well as borderline intellectual functioning and mental retardation. The data indicate that the majority of patients with SFD are given a diagnosis of residual category, such as USFD or SFD-NOS, and that the age of onset varies depending on the diagnostic subtype. SFD was more frequently seen in women, associated with comorbidities.     

Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users

BACKGROUND: Studies in abstinent methamphetamine (METH) users have demonstrated reductions in brain dopamine transporter (DAT) binding potential (BP), as well as cognitive and motor deficits, but it is not yet clear whether cognitive deficits and brain DAT reductions fully reverse with sustained abstinence, or whether behavioral deficits in METH users are related to dopamine (DA) deficits. This study was conducted to further investigate potential persistent psychomotor deficits secondary to METH abuse, and their relationship to brain DAT availability, as measured using quantitative PET methods with [(11)C]WIN 35428. METHODS: Twenty-two abstinent METH users and 17 healthy non-METH using controls underwent psychometric testing to test the hypothesis that METH users would demonstrate selective deficits in neuropsychiatric domains known to involve DA neurons (e.g., working memory, executive function, motor function). A subset of subjects also underwent PET scanning with [(11)C]WIN 35428. RESULTS: METH users were found to have modest deficits in short-term memory, executive function, and manual dexterity. Exploratory correlational analyses revealed that deficits in memory, but not those in executive or motor function, were associated with decreases in striatal DAT BP. CONCLUSIONS: These results suggest a possible relationship between DAT BP and memory deficits in abstinent METH users, and lend support to the notion that METH produces lasting effects on central DA neurons in humans. As METH can also produce toxic effects on serotonin (5-HT) neurons, further study is needed to address the potential role of brain 5-HT depletion in cognitive deficits in abstinent METH users.     

Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal-regulated kinase activation and renal fibrosis

Systemic administration of the potent vasodilating peptide adrenomedullin reduces cardiac and renal fibrosis in hypertensive animals. Here, we investigated the effects of kidney-specific adrenomedullin gene delivery in normotensive rats after unilateral ureteral obstruction, an established model of renal tubulointerstitial fibrosis. Overexpression of exogenous adrenomedullin in the renal interstitium following ureteral obstruction significantly prevented fibrosis and proliferation of tubular and interstitial cells. In this model, there is upregulation of connective tissue growth factor (CTGF) mRNA expression and extracellular signal-regulated kinase (ERK) phosphorylation, and adrenomedullin overexpression suppressed both of these activities without altering the blood pressure. In NRK-49F renal fibroblasts, adrenomedullin reduced transforming growth factor-beta-induced CTGF and fibronectin mRNA upregulation through the cyclic AMP/protein kinase A signaling pathway, and suppressed ERK phosphorylation and cell proliferation. In the kidneys with an obstructed ureter, adrenomedullin receptor gene expression was upregulated along with cyclic AMP production in kidney slices. The latter effect was partially blocked by a neutralizing antibody to adrenomedullin, indicating that an endogenous peptide-receptor system was activated. Our results show that overexpression of exogenous adrenomedullin in the ureteral-obstructed kidney prevents tubulointerstitial fibrosis and cell proliferation through the cyclic AMP-mediated decrease of CTGF induction and ERK phosphorylation.     

Differences in excitability properties of FDI and ADM motor axons

The first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles are innervated by the same ulnar nerve, but studies have shown that the former is much more severely affected in amyotrophic lateral sclerosis. In this study, threshold tracking was used to investigate whether membrane properties differ between FDI and ADM motor axons. In 12 normal subjects, compound muscle action potentials were recorded from FDI and ADM after ulnar nerve stimulation at the wrist. The strength–duration time constant was significantly longer in the FDI axons than in the ADM axons, and latent addition studies showed greater threshold changes at the conditioning–test stimulus of 0.2 ms in FDI than in ADM axons. These findings suggest that nodal persistent sodium conductances are more prominent in FDI axons than in ADM axons, and therefore excitability is physiologically higher in FDI axons. Even in the same nerve at the same sites, membrane properties of FDI and ADM motor axons differ significantly, and thus their axonal/neuronal responses to disease may also differ. Muscle Nerve 39: 350–354, 2009     

Reference serum cystatin C levels in Japanese children

Background  

Single measurements of serum cystatin C (cysC) concentration have generally been used to determine glomerular filtration rate (GFR) in adults. Since GFR varies to some extent among children, we attempted to determine reference serum cysC concentrations for Japanese children.     

Factors impacting on psychological distress and recovery after the 2004 Niigata-Chuetsu earthquake, Japan: community-based study

Aim: This study was undertaken 5 months after the 2004 Niigata–Chuetsu earthquake in Japan to assess factors that impacted on psychological distress and its recovery. Methods: Three thousand and twenty‐six adult victims who lived in temporary shelter and in seriously damaged areas were evaluated by questionnaire. The questionnaire queried subject profile, degree of house damage, health status, and psychological distress using a 5‐point scale before, immediately and 5 months after the earthquake. Results: Immediately after the earthquake, 59.3% of the subjects had psychological distress. At 5 months after the earthquake, however, this percentage decreased to 21.8%. The psychological distress immediately after the earthquake was significantly serious in victims who: (i) were female; (ii) felt stronger fear of the earthquake and the aftershocks; (iii) lived at home or office after the earthquake; and (iv) were injured due to the earthquake or suffered from sickness after the earthquake. In contrast, the factors impairing psychological recovery 5 months after the earthquake were as follows: (i) being with unfamiliar member(s) during the night after the earthquake; (ii) serious house damage; (iii) living in temporary shelter or at a relative's home after the earthquake; and (iv) physical illness after the earthquake. Conclusion: Despite differences between disasters, these results were consistent with those in some previous studies and may be useful for long‐term mental care support.