Circulating levels of DNA-histone complex and dsDNA are independent prognostic factors of disseminated intravascular coagulation

AbstractIntroductionNeutrophils can be induced to release DNA combined with histones. The resulting neutrophil extracellular trap (NET) provides a scaffold for growing hemostatic plug. Therefore, the NET formation may be inevitable in clinical conditions that are characterized by formation of vascular thrombi. Thus far, there have been no reports on the clinical significance of NET in disseminated intravascular coagulation (DIC). Therefore, we investigated circulating levels of NET in DIC and analyzed their potential values to assess coagulation severity and predict clinical outcome.MethodsThe plasma levels of DNA-histone complexes and double-stranded DNA (dsDNA), considered to be in vivo markers of NET, were measured in 199 patients suspected of having DIC and 20 healthy controls.ResultThe circulating levels of DNA-histone complexes and dsDNA were significantly elevated in overt-DIC. The increased levels of these two markers correlated with the severity of coagulopathy including DIC score and D-dimer. Multivariable Cox regression analysis, adjusted for the conventional DIC markers, revealed that elevated DNA-histone complexes and dsDNA are poor independent prognostic markers.ConclusionThe circulating levels of NET release reflect the coagulation activation and adverse clinical outcomes in patients with DIC, thereby providing potential clinical relevance for mortality prediction in DIC

Eosinophilic Otitis Media: CT and MRI Findings and Literature Review

Eosinophilic otitis media (EOM) is a relatively rare, intractable, middle ear disease with extremely viscous mucoid effusion containing eosinophils. EOM is associated with adult bronchial asthma and nasal allergies. Conventional treatments for otitis media with effusion (OME) or for chronic otitis media (COM), like tympanoplasty or mastoidectomy, when performed for the treatment of EOM, can induce severe complications such as deafness. Therefore, it should be differentiated from the usual type of OME or COM. To our knowledge, the clinical and imaging findings of EOM of temporal bone are not well-known to radiologists. We report here the CT and MRI findings of two EOM cases and review the clinical and histopathologic findings of this recently described disease entity

Identification of Domains Directing Specificity of Coupling to G-proteins for the Melanocortin MC3 and MC4 Receptors

The melanocortin receptors, MC3R and MC4R, are G protein-coupled receptors that are involved in regulating energy homeostasis. Using a luciferase reporter gene under the transcriptional control of a cAMP-responsive element (CRE), the coupling efficiency of the MC4R and MC3R to G-proteins was previously shown to be different. MC4R exhibited only 30-50% of the maximum activity induced by MC3R. To assess the role of the different MC3R and MC4R domains in G-protein coupling, several chimeric MC3R/MC4R receptors were constructed. The relative luciferase activities, which were assessed after transfecting the chimeric receptors into HEK 293T cells, showed that the i3 (3rd intracellular) loop domain has an essential role in the differential signaling of MC3R and MC4R. To reveal which amino acid residue was involved in the MC4R-specific signaling in the i3 loop, a series of mutant MC4Rs was constructed. Reporter gene analysis showed that single mutations of Arg220 to Ala and Thr232 to either Val or Ala increased the relative luciferase activities, which suggests that these specific amino acids, Arg220 and Thr232, in the i3 loop of MC4R play crucial roles in G-protein coupling and the subtype-specific signaling pathways. An examination of the inositol phosphate (IP) levels in the cells transfected with either MC3R or MC4R after being exposed to the melanocortin peptides revealed significant stimulation of IP production by MC3R but no detectable increase in IP production was observed by MC4R. Furthermore, none of the MC4R mutants displayed melanocortin peptide-stimulated IP production. Overall, this study demonstrated that MC3R and MC4R have distinct signaling in either the cAMP- or the inositol phospholipid-mediated pathway with different conformational requirements

Genetic variation of aldolase from Korean isolates of Plasmodium vivax and its usefulness in serodiagnosis

Background: The malaria aldolase is widely used as rapid diagnostic test (RDT), but the efficacy in aspect of its serological effectiveness in diagnosis is not known. The genetic variation of Korean isolates was analysed and recombinant aldolase was evaluated as a serological antigen in Plasmodium vivax malaria. Methods: Genomic DNA was purified and the aldolase gene of P. vivax from 25 patients’ blood samples was amplified. The samples came from 5 epidemic areas; Bucheon-si, Gimpo-si, Paju-si of Gyeonggido, Gangwha-gun of Incheon metropolitan city, and Cheorwon of Gangwon-do, South Korea. The antigenicity of the recombinant aldolase was tested by western blot and enzyme-linked immunosorbent assay (ELISA). Results: Sequence analysis of 25 Korean isolates of P. vivax showed that the open reading frame (ORF) of 1,110 nucleotides encoded a deduced protein of 369 amino acids (aa). This ORF showed 100% homology with the P. vivax Sal I strain (XM_00165894) and P. vivax WDK strain (AF247063), 87.4% homology with Plasmodium falciparum (AF179421), 90.6% homology with Plasmodium chabaudi (AF247060), 89.5% homology with Plasmodium vinckei (AF247061), and 96.7% homology with Plasmodium knowlesi. A single nucleotide polymorphism (SNP) at nucleotide 180 (G to A, n = 5) was also observed in the isolates. The expressed recombinant protein had a molecular weight of approximately 31 kDa (monomeric form) and 62 kDa (dimeric form) as analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. Among 109 P. vivax patients, 32 (29.4%) had positive in an enzyme-linked absorbance assay (ELISA). This result showed significant correlation between ELISA and an indirect fluorescent antibody test (IFAT) (P < 0.0001). Conclusions: The aldolase gene from Korean isolates of P. vivax showed one SNP at nucleotide position 180; this SNP mutant was discovered in only the western part of Han River, and included the regions of Ganghwa, Gimpo, and Bucheon. Based on the results, the relationship between antibody production against aldolase and the pattern of disease onset should be more investigated before using aldolase for serodiagnosis

Seasonal Prevalence of Mosquitoes, Including Vectors of Brugian Filariasis, in Southern Islands of the Republic of Korea

A survey of mosquitoes, including the vector status of Brugia malayi filariasis and their relative larval density, was conducted from 2002 to 2005 at several southern remote islands of Jeollanam-do (province), Gyeongsangnam-do, and Jeju-do, Korea, where filariasis was previously endemic. Overall, a total of 9 species belonging to 7 genera were collected. Ochlerotatus togoi (formerly known as Aedes togoi), Anopheles (Hyrcanus) group, and Culex pipiens were the predominant species captured at all areas. Oc. togoi larvae were most frequently collected at salinity levels <0.5% during June and July, with densities decreasing sharply during the rainy season in August. The most likely explanation for the eradication of filariasis in these areas is suggested to be an aggressive treatment program executed during the 1970s and the 1990s. However, high prevalence of the vector mosquitoes may constitute a potential risk for reemerging of brugian filariasis in these areas

Osteitis Fibrosa Cystica Mistaken for Malignant Disease

A 65-year-old man with back pain had plain radiographs that showed multiple osteolytic bone lesions of the pelvis, femur and L-spine; an magnetic resonance imaging scan of the L-spine showed extensive bony resorption with a posterior epidural mass involving the L1 spinous process; these findings suggested multiple myeloma or bony metastasis. However, all serology testing was negative. The parathyroid hormone and serum calcium levels were found to be abnormally elevated. A fine needle aspiration biopsy suggested that the L-spine lesion was consistent with the diagnosis of osteitis fibrosa cystica. A pathological fracture of the spine compressed the spinal cord, and surgical intervention was required. The neck computed tomography and Tc-99m sestamibi scan showed a solitary parathyroid mass. A minimally invasive parathyroidectomy using intraoperative parathyroid hormone monitoring was performed and two enlarged parathyroid glands identified. This case illustrates the importance of the consideration of a rare brown tumor associated with primary hyperparathyroidism in patients with the bone lesions suggestive of a malignancy

Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin