Cerebral Infarction in IgG Multiple Myeloma with Hyperviscosity

Cerebral infarction is an uncommon complication in multiple myeloma with hyperviscosity. Serum hyperviscosity may cause a variety of clinical manifestations including bleeding from mucosal membranes, congestive heart failure, retinopathy, and various neurologic deficits. These manifestations have been attributed to the presence of large quantities of asymmetrical molecules of high molecular weight in the serum. We recently experienced a case of multiple myeloma with acute cerebral infarction, which caused by hyperviscosity, as an initial manifestation in IgG multiple myeloma, and reviewed the relevant literature of myeloma presenting with the stroke. A 68-yr-old woman abruptly developed hypesthesia and monoplegia in the left leg. The stroke confirmed by the brain MRI and MR angiography, which revealed acute infarction at the right anterior cerebral artery territory. On admission, routine blood tests showed a slight decrease in hemoglobin and a marked increase in erythrocyte sedimentation rate. Peripheral blood smear, serum protein electrophoresis, serum visocity, and bone marrow aspiration showed that she had IgG multiple myeloma with hyperviscosity. She was treated by chemotherapy with cyclophosphamide and discharged with the improved clinical condition

The Association between Intraocular Pressure and Predictors of Coronary Heart Disease Risk in Koreans

Elevated intraocular pressure (IOP) is one of the major risk factors for glaucomatous visual field defects. Each individual systemic risk factor of coronary heart disease (CHD) is associated with elevated IOP, although no reports have argued for a correlation between the risk factors for CHD and IOP after a comprehensive or collective analysis. The National Cholesterol Education Program Adult Treatment Panel III presented the Framingham projection, which can predict the risk of CHD quantitatively. We investigated the association between IOP and the Framingham projection in 16,383 Korean subjects. The Framingham projection was applied using the indicated risk factors. The associations between the Framingham projection and IOP and the influences of the risk factors on the IOP were examined. The Framingham projection was correlated with the mean IOP in women (p<0.05). The relationship between IOP and systemic variables other than smoking was significant (p<0.05). The mean IOP was significantly higher in the high-risk CHD group than in the low-risk group based on the Framingham projection (p<0.05). Because an elevated IOP was associated with cardiovascular risk factors, subjects with a high CHD risk based on the Framingham projection need continuous monitoring for IOP to prevent glaucomatous visual field defects

Association of the Oncostatin M Receptor Gene Polymorphisms with Papillary Thyroid Cancer in the Korean Population

ObjectivesTo investigate the association between papillary thyroid cancer (PTC) and single nucleotide polymorphisms (SNPs) of oncostatin M receptor (OSMR) in the Korean population.MethodsRetrospective case-control study was done. Eighty-five patients with PTC and 287 controls were studied. One missense SNP (rs2278329, Asp553Asn) and one promoter SNP (rs2292016, -100 G/T) of the OSMR gene were genotyped by direct sequencing. Genetic data were analyzed using the SNPStats, Helixtree, and SNPAnalyzer Pro. PTC patients were dichotomized and compared with respect to the clinicopathologic characteristics.ResultsThere was no association between genotypes and allele frequencies of OSMR SNPs (rs2278329 and rs2292016) and PTC susceptibility. SNP rs2278329 was significantly associated with tumor size (dominant model; P=0.028; odds ratio [OR], 2.71; 95% confidence interval [CI], 1.12 to 6.57). The A allele was higher in sizes large than 1 cm (32.5% vs. 16.7%; P=0.018; OR, 2.41; 95% CI, 1.17 to 4.98). Regarding the number of tumors, we found no significant association with genotype, however, the A allele was higher in patients with multifocaltiy (33.3% vs. 19.1%; P=0.040; OR, 2.12; 95% CI, 1.03 to 4.34).ConclusionThe results suggest that OSMR polymorphism rs2278329 is associated with clinicopathologic characteristics of the tumor growth and multifocality development

Congenital Acute Myeloid Leukemia with t(8;16) and t(17;19) Double Translocation: Case Presentation and Literature Review

Congenital leukemia is uncommon and excluding transient myeloproliferation associated with Down syndrome, makes up approximately 1% of childhood leukemias. A newborn boy was born with multiple subcutaneous nodules and large purpuric papules. Skin biopsy revealed proliferation of atypical hematologic cells in the dermis. Bone marrow morphology was consistent with acute myeloid leukemia (M5) and cytogenetic studies revealed t(8;16) and t(17;19) double translocation. Although prognosis of congenital leukemia is known to be dismal, recent reports showed spontaneous remissions. With the fear of chemotherapy-related toxicity, to treat or not to treat may be a dilemma both to parents and pediatricians. We report our experience and review the literature

Mesoscopic organization reveals the constraints governing C. elegans nervous system

One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations, such as optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis, we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key functional role as a processor of information.Comment: Published version, Minor modifications, 16 pages, 9 figure

A comparison of missing data methods for hypothesis tests of the treatment effect in substance abuse clinical trials: a Monte-Carlo simulation study

<p>Abstract</p> <p>Background</p> <p>Missing data due to attrition are rampant in substance abuse clinical trials. However, missing data are often ignored in the presentation of substance abuse clinical trials. This paper demonstrates missing data methods which may be used for hypothesis testing.</p> <p>Methods</p> <p>Methods involving stratifying and weighting individuals based on missing data pattern are shown to produce tests that are robust to missing data mechanisms in terms of Type I error and power. In this article, we describe several methods of combining data that may be used for testing hypotheses of the treatment effect. Furthermore, illustrations of each test's Type I error and power under different missing data percentages and mechanisms are quantified using a Monte-Carlo simulation study.</p> <p>Results</p> <p>Type I error rates were similar for each method, while powers depended on missing data assumptions. Specifically, power was greatest for the weighted, compared to un-weighted methods, especially for greater missing data percentages.</p> <p>Conclusion</p> <p>Results of this study as well as extant literature demonstrate the need for standards of design and analysis specific to substance abuse clinical trials. Given the known substantial attrition rates and concern for the missing data mechanism in substance abuse clinical trials, investigators need to incorporate missing data methods a priori. That is, missing data methods should be specified at the outset of the study and not after the data have been collected.</p

Structural and functional basis for RNA cleavage by Ire1

BACKGROUND: The unfolded protein response (UPR) controls the protein folding capacity of the endoplasmic reticulum (ER). Central to this signaling pathway is the ER-resident bifunctional transmembrane kinase/endoribonuclease Ire1. The endoribonuclease (RNase) domain of Ire1 initiates a non-conventional mRNA splicing reaction, leading to the production of a transcription factor that controls UPR target genes. The mRNA splicing reaction is an obligatory step of Ire1 signaling, yet its mechanism has remained poorly understood due to the absence of substrate-bound crystal structures of Ire1, the lack of structural similarity between Ire1 and other RNases, and a scarcity of quantitative enzymological data. Here, we experimentally define the active site of Ire1 RNase and quantitatively evaluate the contribution of the key active site residues to catalysis. RESULTS: This analysis and two new crystal structures suggest that Ire1 RNase uses histidine H1061 and tyrosine Y1043 as the general acid-general base pair contributing \u3e/=7.6 kcal/mol and 1.4 kcal/mol to transition state stabilization, respectively, and asparagine N1057 and arginine R1056 for coordination of the scissile phosphate. Investigation of the stem-loop recognition revealed that additionally to the stem-loops derived from the classic Ire1 substrates HAC1 and Xbp1 mRNA, Ire1 can site-specifically and rapidly cleave anticodon stem-loop (ASL) of unmodified tRNAPhe, extending known substrate specificity of Ire1 RNase. CONCLUSIONS: Our data define the catalytic center of Ire1 RNase and suggest a mechanism of RNA cleavage: each RNase monomer apparently contains a separate catalytic apparatus for RNA cleavage, whereas two RNase subunits contribute to RNA stem-loop docking. Conservation of the key residues among Ire1 homologues suggests that the mechanism elucidated here for yeast Ire1 applies to Ire1 in metazoan cells, and to the only known Ire1 homologue RNase L