A case of bilateral limbic and recurrent unilateral cortical encephalitis with anti-myelin oligodendrocyte glycoprotein antibody positivity.

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody can be detected not only in acute disseminated encephalomyelitis or optic neuritis but also in limbic or cortical encephalitis. However, no previous reports have demonstrated a relapsing case of these two types of encephalitis. CASE REPORT: An 11-year-old girl presented with fever, headache, abnormal behavior, focal impaired awareness seizures (FIAS) on the left side, and MRI hyperintensities in the bilateral amygdala, hippocampus, and right posterior temporal cortex. The symptoms were alleviated with two courses of intravenous methylprednisolone (IVMP) and one course of immunoglobulin. At 16 years of age, the patient returned with left-sided headache and MRI hyperintensities in the left temporal, parietal, and insular cortices, which improved after 3 courses of IVMP. Oral prednisolone (PSL) was tapered over 6 months, when FIAS reappeared on the right side of the body. MRI showed recurrence in the same regions as in the second episode. She received 3 courses of IVMP, followed by gradually tapered PSL without relapse for 1.5 year. Anti-MOG antibodies were positive in both serum and the cerebrospinal fluid prior to treatment in all three episodes. CONCLUSION: Our results revealed that anti-MOG antibody-related bilateral limbic and unilateral cortical encephalitis can manifest with a variety of phenotypes over time in the same patient.

Community-acquired pneumonia distinguished from influenza infection based on clinical signs and symptoms during a novel (swine) influenza A/H1N1 pandemic.

AIMS: The numbers of patients with influenza-like illnesses increase during influenza outbreaks. A study was undertaken to distinguish community-acquired pneumonia (CAP) from influenza based on clinical signs and symptoms. METHODS: This retrospective study investigated patients with positive results in the rapid influenza antigen test and those diagnosed with CAP during an influenza A/H1N1 pandemic. Significant factors for predicting risk for CAP within 48 hrs from onset and at diagnosis were selected by multiple regression analysis. RESULTS: Within 48 hrs of onset and at diagnosis, age and coarse crackles significantly increased the risk of CAP whereas sick contact, sore throat, and rhinorrhoea significantly decreased the risk of CAP. Duration of illness, sputum, dyspnoea, chest pain, and coarse crackles also significantly increased the risk of CAP at diagnosis. CONCLUSIONS: CAP differed somewhat from influenza even within 48 hrs of onset and the differences became even more evident thereafter.

Significance of the progression of respiratory symptoms for predicting community-acquired pneumonia in general practice.

BACKGROUND AND OBJECTIVE: Early diagnosis improves outcomes in patients with community-acquired pneumonia (CAP). However, prediction of CAP based on symptoms and signs is difficult. The present study investigated the evaluation of progression of symptoms as a factor for predicting the occurrence of CAP in general practice. METHODS: Consecutive patients (n = 406) suspected of having CAP on routine clinical examination were studied retrospectively. Selection of patients with suspected CAP was based on progression of symptoms after 5 days, as well as published criteria. Diagnostic yields for the recommended criteria and our proposed criteria were then compared. Scoring systems for the prediction of CAP were designed, based on the results of multiple regression analysis. The diagnostic performance of these systems, including or excluding symptom progression, was compared using the areas under receiver operating characteristic curves. RESULTS: The sensitivity and specificity of the recommended criteria and our proposed criteria were 0.75 and 0.44, and 0.93 and 0.38, respectively. Sputum production, dyspnoea, fever > 38 degrees C, heart rate > 100 beats/min, decreased breath sounds, coarse crackles and progression of symptoms significantly increased the likelihood of CAP. Areas under receiver operating characteristic curves analysis showed that the diagnostic prediction of CAP was significantly improved when the scoring system included progression of symptoms. CONCLUSIONS: Progression of symptoms was a significant factor for predicting CAP and selecting patients who required CXR. Inclusion of progression of symptoms among the other recommended criteria, namely, dyspnoea, fever > 38 degrees C, heart rate > 100 beats/min and abnormal chest findings, improved prediction of the incidence of CAP in general practice.

Crystallization and X-ray diffraction analysis of the RNA primer/promoter-binding domain of influenza A virus RNA-dependent RNA polymerase PB2.

The C-terminal domain protein (amino-acid residues 535-759) of the PB2 subunit of the RNA-dependent RNA polymerase from the highly pathogenic influenza A virus was expressed as a soluble protein in Escherichia coli and crystallized using sodium formate as a precipitant. Data sets were collected from crystals of native and selenomethionine-substituted protein on the KEK NW12 beamline at the Photon Factory and the crystals diffracted to a maximum resolution of 2.44 A for the SeMet-derivative crystal. The native crystals were found to belong to space group P3(2)21, with unit-cell parameters a = b = 52.5, c = 156.3 A. The Matthews value (V(M)) was 2.7 A(3) Da(-1), assuming the presence of one molecule in the asymmetric unit. The SeMet-derivative crystals were found to belong to the same space group, with unit-cell parameters a = b = 52.6, c = 156.4 A. Attempts are being made to solve the structure by multi-wavelength anomalous dispersion phasing.

Structural basis of the influenza A virus RNA polymerase PB2 RNA-binding domain containing the pathogenicity-determinant lysine 627 residue.

Because the influenza A virus has an RNA genome, its RNA-dependent RNA polymerase, comprising the PA, PB1, and PB2 subunits, is essential for viral transcription and replication. The binding of RNA primers/promoters to the polymerases is an initiation step in viral transcription. In our current study, we reveal the 2.7 A tertiary structure of the C-terminal RNA-binding domain of PB2 by x-ray crystallography. This domain incorporates lysine 627 of PB2, and this residue is associated with the high pathogenicity and host range restriction of influenza A virus. We found from our current analyses that this lysine is located in a unique "phi"-shaped structure consisting of a helix and an encircled loop within the PB2 domain. By electrostatic analysis, we identified a highly basic groove along with this phi loop and found that lysine 627 is located in the phi loop. A PB2 domain mutant in which glutamic acid is substituted at position 627 shows significantly lower RNA binding activity. This is the first report to show a relationship between RNA binding activity and the pathogenicity-determinant lysine 627. Using the Matras program for protein three-dimensional structural comparisons, we further found that the helix bundles in the PB2 domain are similar to that of activator 1, the 40-kDa subunit of DNA replication clamp loader (replication factor C), which is also an RNA-binding protein. This suggests a functional and structural relationship between the RNA-binding mechanisms underlying both influenza A viral transcription and cellular DNA replication. Our present results thus provide important new information for developing novel drugs that target the primer/promoter RNA binding of viral RNA polymerases.

Increased circulating matrix metalloproteinase-2 in patients with hypertrophic cardiomyopathy with systolic dysfunction.

BACKGROUND: Some patients with hypertrophic cardiomyopathy (HCM) develop left ventricular (LV) wall thinning associated with LV dilatation and systolic dysfunction. Recently, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were reported to be involved in ventricular remodeling, however, little is known about MMPs and TIMPs in patients with HCM. METHODS AND RESULTS: Enzyme-linked immunoassays were used to measure the plasma concentrations of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 in 11 patients with HCM accompanied by systolic dysfunction (fractional shortening (FS) <25%, group A), 17 patients with HCM who had preserved systolic function (FS> or =25%, group B), and 50 age-matched clinically healthy control subjects (mean age: 57 years). The concentration of MMP-2 in group A was significantly higher than in group B and the control subjects (1,124 +/- 84, 792 +/- 49, 809 +/- 26 ng/ml, respectively), whereas there was no significant difference between group B and the control subjects. MMP-2 concentrations significantly increased as the New York Heart Association functional class increased in patients with HCM. TIMP-2 was also significantly higher in group A patients than in group B and the control subjects (45.3 +/- 4.7, 34.6 +/- 2.2, 33.7 +/- 1.8 ng/ml, respectively), but there was no difference between group B and control subjects. TIMP-1 was significantly higher in HCM patients than in control subjects. MMP-3 and MMP-9 concentrations did not differ among the 3 groups. Both MMP-2 and TIMP-2 correlated significantly with FS and LV dimension, negatively and positively, respectively. CONCLUSIONS: These results suggest that changes in the release and activity of MMP-2 and TIMP-2 may be associated with the mechanisms responsible for cardiac remodeling in patients with HCM.