Isolated pyramidal tract impairment in the central nervous system of adult-onset Krabbe disease with novel mutations in the GALC gene

This report describes a 60-year-old female patient with Krabbe disease who presented with slowly progressive gait disturbance due to mild spastic paraplegia. Brain magnetic resonance imaging showed high-intensity lesions along the upper parts of the bilateral pyramidal tracts in fluid-attenuated inversion recovery images. Central motor conduction time was prolonged both in the upper and the lower extremities, while central sensory conduction time was normal. The reduced lymphocyte galactocerebrosidase (GALC) activity and two novel mutations in the GALC gene, p.G496S and p.G569S, proved the diagnosis of Krabbe disease. Our findings show that adult-onset Krabbe disease is characterized by isolated pyramidal tract impairment in the central nervous system, both neurophysiologically and radiologically.     

Distribution and immunohistochemical localization of GDNF protein in selected neural and non-neural tissues of rats during development and changes in unilateral 6-hydroxydopamine lesions

The tissue distribution of glial cell line-derived neurotrophic factor (GDNF) during development and changes in GDNF levels by unilateral 6-hydroxydopamine lesions were investigated in rats using a newly established enzyme immunoassay system and by immunohistochemistry. The detection limit of the assay was 0.3 pg/0.2 ml and the system recognized glycosylated mature GDNF. Concentrations of GDNF were relatively high in the kidney and testis during the embryonic and neonatal periods, respectively, and decreased with age. In the striatum, hippocampus and brain stem, GDNF reached a maximal level at around postnatal day 14. However, brain levels were generally lower than those in non-neural tissues. In the CNS, GDNF immunoreactivity was observed in striatal neurons, pyramidal neurons in the hippocampus and the Vth layer of the cortex, large neurons in the diagonal band and brain stem, and spinal motor neurons. It was also evident in several non-neural, tissue-specific cells, such as cells in the renal collecting ducts and distal tubules, and testicular Sertoli cells. Destruction of nigral dopaminergic neurons by 6-hydroxydopamine enhanced the levels of striatal GDNF protein, with apparent involvement of astrocytes. These results suggest that GDNF is normally synthesized in neurons, but may also be produced by astroglial cells in damaged brains.     

Beijing family and other genotypes of Mycobacterium tuberculosis isolates in Okayama district

OBJECTIVE: The purpose of this study is to investigate the distribution of Mycobacterium tuberculosis genotypes, such as Beijing family and other genotypes in Okayama district, and to examine the relation between these genotype strains and prevalent strains. METHODS: The 142 M. tuberculosis strains isolated in Okayama City from January 2000 to December 2002 were subjected to IS6110-RFLP and spoligotyping for the population-based study. In addition, 13 strains having 1 to 5 IS6110 copies isolated in Okayama Prefecture excluding Okayama City were also subjected to spoligotyping. RESULTS: A total of 103 (72.5%) of 142 strains belonged to Beijing family. Furthermore, 3 of 4 groups of prevalent strains belonged to the family. Twenty one strains out of 39 rest strains could be classified into 10 shared types (STs) of 259 STs in the worldwide spoligotype database. In addition, 15 out of 26 strains from inside and outside of Okayama City having 1 to 5 IS6110 copies showed common unique spoligotype. Moreover, the age of majority patients who were infected with M. tuberculosis of the Beijing family or other genotypes were older than 60 years. CONCLUSION: It was suggested that Beijing family had been the main infection source, and the spread of strains of Beijing family and other genotypes occurred considerably in old times, and the unique genotype strains remained for a long time as peculiar strains.     

Behavioral outcome including attention deficit hyperactivity disorder/hyperactivity disorder and minor neurological signs in perinatal high-risk newborns at 4−6 years of age with relation to risk factors

BACKGROUND: Diagnostic problems with the criteria of attention deficit hyperactivity disorder (ADHD) in the Diagnostic Statistical Manual, 4th edn, have been identified. The aim of this study was to clarify whether the minor neurological signs test (MNT) the authors had previously reported was a predictor for the criteria of ADHD or hyperactivity disorder (HD) in perinatal risk children at 4-6 years of age and what kind of risk factors related to MNT. METHODS: A total of 136 children discharged from neonatal intensive care units were examined at the age of 4-6 years by a developmental neuropediatrician using both MNT and diagnostic criteria of DSM-IV ADHD/ICD-10 (International Classification of Diseases, 10th edn) HD. SPSS base and professional were used for statistical analysis. RESULTS: On comparison of diagnostic criteria between ADHD (11.0%) and HD (27.5%), the incidence in the same subjects showed significant difference. MNT scores showed significant correlation with criteria of ADHD (P < 0.01) and HD (P < 0.05). Diagnostic validity of MNT for predicting ADHD was demonstrated with 78% sensitivity and 79% specificity. High positive rates on MNT did not show a significant difference between the very low birthweight (VLBW) and non-low birthweight (NLBW) groups. Behavioral outcome with relation to risk factors were analyzed using multiple regression analysis. Apgar 5 in the NLBW group and toxemia of pregnancy and small for gestational age (SGA) in VLBW group were highly correlated with behavioral outcome. CONCLUSIONS: Minor neurological signs test score was a significant predictor for criteria of ADHD and HD. High incidences of positive MNT were suspected in not only VLBW children but also NLBW children and Apgar 5 in NLBW children and toxemia of pregnancy and SGA in VLBW children influenced behavioral outcome.     

PKC- and PI3K-dependent but ERK-independent proliferation of murine splenic B cells stimulated by chondroitin sulfate B

High molecular weight polyanions such as dextran sulfate are known to be weak polyclonal activators of murine B cells, but the molecular mechanism of their mitogenic activitiy is not fully elucidated. Although chondroitin sulfate A (CSA), B (CSB) and C (CSC) are highly charged polyanions, little is known about their effects on the proliferation of B cells. In this study, we demonstrated that CSB stimulated proliferation of murine B cells as markedly as did anti-IgM antibody, more markedly than did dextran sulfate and much more markedly than did CSA, CSC, heparin and hyaluronic acid. CSB caused translocation of protein kinase C (PKC) isoform beta from cytosol to membrane fractions and increased phosphorylation of Akt but not phosphorylation of extracellular signal-regulated kinase (ERK) of B cells. CSB-induced B cell proliferation was almost completely blocked by either the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or the PKC inhibitor GF109203X but was not significantly inhibited by the ERK kinase inhibitor PD98059. The mitogenic effect of anti-IgM was significantly inhibited by all the three inhibitors, while the mitogenic effect of LPS was inhibited only by LY294002. These findings indicate that CSB stimulated proliferation of murine B cells more markedly than did dextran sulfate and suggest that PKC and PI3K are crucial but that ERK is less important for the mitogenic activity of CSB, the signaling pathways of which may be at least partly distinct from those of anti-IgM and LPS.     

Effect of low-frequency repetitive transcranial magnetic stimulation on interhemispheric inhibition

We studied the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) on the excitability of interhemispheric connections in 13 right-handed healthy volunteers. TMS was performed using figure-eight coils, and surface electromyography (EMG) was recorded from both first dorsal interosseous (FDI) muscles. A paired-pulse method with a conditioning stimulus (CS) to the motor cortex (M1) followed by a test stimulus to the opposite M1 was used to study the interhemispheric inhibition (ppIHI). Both CS and TS were adjusted to produce motor-evoked potentials of approximately 1 mV in the contralateral FDI muscles. After baseline measurement of right-to-left IHI (pre-RIHI) and left-to-right IHI (pre-LIHI), rTMS was applied over left M1 at 1 Hz with 900 stimuli at 115% of resting motor threshold. After rTMS, ppIHI was studied using both the pre-rTMS CS (post-RIHI and post-LIHI) and an adjusted post-rTMS CS set to produce 1-mV motor evoked potentials (MEPs; post-RIHI(adj) and post-LIHI(adj)). The TS was set to produce 1-mV MEPs. There was a significant reduction in post-LIHI (P = 0.0049) and post-LIHI(adj) (P = 0.0169) compared with pre-LIHI at both interstimulus intervals of 10 and 40 ms. Post-RIHI was significantly reduced compared with pre-RIHI (P = 0.0015) but pre-RIHI and post-RIHI(adj) were not significantly different. We conclude that 1-Hz rTMS reduces IHI in both directions but is predominantly from the stimulated to the unstimulated hemisphere. Low-frequency rTMS may be used to modulate the excitability of IHI circuits. Treatment protocols using low-frequency rTMS to reduce cortical excitability in neurological and psychiatric conditions need to take into account their effects on IHI.     

The performance of the automated immune chemiluminescent system "IMMULITE 2000XPi for the measurement of serum soluble IL-2 receptor in clinical samples

The performance of a chemical luminescence test reagent "Immulyze IL-2R II" with an automated immune chemiluminescent system "IMMULITE 2000XPi" for the measurement of serum soluble IL-2 receptor in clinical samples was investigated. The satisfactory results were obtained for the reproducibility, precision, linearity, and sensitivity, and no interference with hemolysis, bilirubin, chyle or intrafat was observed. A significant correlation was found between the values of sIL-2R measured by the Cell-free N IL-2R and those obtained by the IMMULYZE IL-2R II. The measurements were stable regardless of the methods of sample preservation, or repeated freeze-thawing procedures. Elevated concentrations of sIL-2R over 1,000 U/mL were found in multiple types of collagen diseases or severe cases of allergic diseases, indicative that sIL-2R levels might correlate with the severity of autoimmune diseases. In patients with lymphoma, sIL-2R levels correlated with the lactate dehydrogenase (LD) activity. Among the lymphoma cases with sIL-2R levels over 1,000 U/mL, the majority (84%) had significantly higher levels of LD, and among them, 81% were at the clinical stage IV. We observed that sIL-2R levels increased from the early stages of lymphoma, while LD activities increased at the advanced stages. Our present findings suggest that sIL-2R is a promising marker for the diagnosis of autoimmune and allergic diseases, and also for the diagnosis and staging of lymphomas.