The association between olfactory bulb volume, cognitive dysfunction, physical disability and depression in multiple sclerosis.

BACKGROUND AND PURPOSE: Olfactory bulb atrophy is associated with cognitive dysfunction in Parkinson's and Alzheimer's disease, and with major depression. It has been suggested that olfactory bulb atrophy or dysfunction is therefore a marker of neurodegeneration. Multiple sclerosis (MS) is now also recognized as having a significant neurodegenerative component. Thus, the aim of this study was to investigate associations between physical and cognitive disability, depression and olfactory bulb volume in MS. METHODS: In total, 146 patients with MS (mean age 49.0 ± 10.9 years, disease duration 21.2 ± 9.3 years, median Expanded Disability Status Scale (EDSS) score 3.0 (range 0-7.5), 103 relapsing-remitting, 35 secondary progressive and eight primary progressive MS) underwent a standardized neurological examination, comprehensive neuropsychological testing and magnetic resonance imaging (MRI); data of 27 healthy people served as age- and gender-matched control subjects. The olfactory bulb was semi-automatically segmented on high-resolution three-dimensional T1-weighted MRI. RESULTS: Mean olfactory bulb volume was lower in MS patients than healthy controls (183.9 ± 40.1 vs. 209.2 ± 59.3 µl; P = 0.018 adjusted to intracranial volume). Olfactory bulb volume was similar across clinical disease subtypes and did not correlate with cognitive performance, EDSS scores or total proton density/T2 white matter lesion volume. However, in progressive MS, the mean olfactory bulb volume correlated with depression scores (Spearman's rho = -0.38, P < 0.05) confirmed using a multivariate linear regression analysis including cognitive fatigue scores. This association was not observed in relapsing-remitting MS. CONCLUSION: Olfactory bulb volume was lower in MS than in healthy controls. Olfactory bulb volume does not seem to mirror cognitive impairment in MS; however, it is associated with higher depression scores in progressive MS.

Fission yeast Eso1p is required for establishing sister chromatid cohesion during S phase.

Sister chromatid cohesion is essential for cell viability. We have isolated a novel temperature-sensitive lethal mutant named eso1-H17 that displays spindle assembly checkpoint-dependent mitotic delay and abnormal chromosome segregation. At the permissive temperature, the eso1-H17 mutant shows mild sensitivity to UV irradiation and DNA-damaging chemicals. At the nonpermissive temperature, the mutant is arrested in M phase with a viability loss due to a failure to establish sister chromatid cohesion during S phase. The lethal M-phase arrest phenotype, however, is suppressed by inactivation of a spindle checkpoint. The eso1(+) gene is not essential for the onset and progression of DNA replication but has remarkable genetic interactions with those genes regulating the G(1)-S transition and DNA replication. The N-terminal two-thirds of Eso1p is highly homologous to DNA polymerase eta of budding yeast and humans, and the C-terminal one-third is homologous to budding yeast Eco1p (also called Ctf7p), which is required for the establishment of sister chromatid cohesion. Deletion analysis and determination of the mutation site reveal that the function of the Eco1p/Ctf7p-homologous domain is necessary and sufficient for sister chromatid cohesion. On the other hand, deletion of the DNA polymerase eta domain in Eso1p increases sensitivity to UV irradiation. These results indicate that Eso1p plays a dual role during DNA replication. The C-terminal region acts to establish sister chromatid cohesion, and the N-terminal region presumably catalyzes translesion DNA synthesis when template DNA contains lesions that block regular DNA replication.

Loop-mediated isothermal amplification of DNA.

We have developed a novel method, termed loop-mediated isothermal amplification (LAMP), that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions. This method employs a DNA polymerase and a set of four specially designed primers that recognize a total of six distinct sequences on the target DNA. An inner primer containing sequences of the sense and antisense strands of the target DNA initiates LAMP. The following strand displacement DNA synthesis primed by an outer primer releases a single-stranded DNA. This serves as template for DNA synthesis primed by the second inner and outer primers that hybridize to the other end of the target, which produces a stem-loop DNA structure. In subsequent LAMP cycling one inner primer hybridizes to the loop on the product and initiates displacement DNA synthesis, yielding the original stem-loop DNA and a new stem-loop DNA with a stem twice as long. The cycling reaction continues with accumulation of 10(9) copies of target in less than an hour. The final products are stem-loop DNAs with several inverted repeats of the target and cauliflower-like structures with multiple loops formed by annealing between alternately inverted repeats of the target in the same strand. Because LAMP recognizes the target by six distinct sequences initially and by four distinct sequences afterwards, it is expected to amplify the target sequence with high selectivity.

[How people process increasing amounts of information as trials go on: reduction of the trade-off between memory and information-processing in the mental resources].

In solving problems in which the amount of memory required increases during the course of solution the subjects would select such strategies as to cope with the deterioration of performance due to the trade-off between the memory load and the information-processing efficiency. To test the above hypothesis 58 graduates and undergraduates were asked to solve a number-guessing problem. In Experiment I, the subjects' responses were categorized and two different information-processing strategies were extracted; the condensation-of-information strategy and the partiality-decision strategy. These strategies were coded as flow charts. In Experiment II, to clarify the relation between processing and memory strategies, memory load was varied by giving the subjects different amount of cues for the solution. Results suggested that the subjects coped flexibly with the demand of situation by adaptive usage of two-layer solving strategies corresponding to the amount of memory load; one was a memory strategy and the other was a processing strategy.

A calcium-binding protein with four EF-hand motifs in Streptomyces ambofaciens.

A gene (cabA) encoding a calcium-binding protein was cloned from Streptomyces ambofaciens. CabA was 180 amino acid residues long and contained four typical EF-hand motifs bearing high sequence similarity to the calcium-binding sites in calmodulin. Consistent with this, CabA showed distinct calcium-binding activity, comparable to bovine brain calmodulin. cabA was transcribed throughout growth, as found by S1 nuclease mapping. Southern hybridization experiments showed that a single copy of cabA was present in various Streptomyces species. A hypothetical relationship between CabA and aerial mycelium formation in this strain was examined, since S. ambofaciens showed calcium-dependent aerial mycelium formation. However, disruption of cabA or overexpression of cabA in S. ambofaciens caused no detectable phenotypic changes.

Are proinflammatory cytokine concentrations reduced by plasma exchange in patients with severe acute hepatic failure?

We studied citric acid levels and proinflammatory cytokines (TNF-alpha, IL-6, and IL-8) before and after plasma exchange in 8 patients with acute liver failure. Plasma exchange was performed over a 6 to 7-hour period. At each session, 3.6 to 4.0 1 of plasma was exchanged for the same volume of fresh frozen plasma (FFP). The concentrations of citric acid were significantly increased after plasma exchange above concentrations before exchange (p<0.0001). There were no significant differences in TNF-alpha, IL-6, or IL-8 concentrations (p=0.7222, p=0.9357, p=0.6394, respectively). Thus, plasma exchange with FFP alone may not effectively remove cytokines.

Molecular cloning of cDNAs of mouse peptidylarginine deiminase type I, type III and type IV, and the expression pattern of type I in mouse.

Peptidylarginine deiminases (PADs), a group of post-translational enzymes, catalyze the conversion of protein-bound arginine residues to citrulline residues in a calcium ion-dependent manner and are widely distributed in various organs of vertebrates. Although the existence of four isoforms of PAD (types I, II, III, and IV) is reported in rodents, the relative functions of the isoforms with respect to their colocation in the tissues have yet to be explored. In this study, we cloned the full-length cDNA encoding mouse PAD type I by screening a uterine cDNA library and using the RACE method. This cDNA consists of an open reading frame of 1989 bases encoding 662 amino acids (73,823 Da), a 5'-untranslated region of 127 bases and a 3'-untranslated region of 1639 bases. Comparative reverse transcription-PCR and Northern-blot analyses detected PAD type I mRNA only in the epidermis and uterus. Administration of estrogen to adult ovariectomized mice increased the content of PAD type I mRNA in the uterus, providing evidence that its expression is under the control of the sex steroid hormone. We also cloned the full-length cDNAs of mouse PAD type III and type IV by the reverse transcription-PCR and RACE methods. The primary structure of PAD type III contains 664 amino acids (75,098 Da) deduced from the coding region of 1995 bases, and the primary structure of PAD type IV consists of 666 amino acids (74,475 Da) deduced from the coding region of 2001 bases. Comparison of the deduced amino acid sequences of all four isoforms of PAD showed about 50% identity with each other, the 3' regions being highly homologous compared with the 5' regions.