Genes in one megabase of the HLA class I region.

To define the gene content of the HLA class I region, cDNA selection was applied to three overlapping yeast artificial chromosomes (YACs) that spanned 1 megabase (Mb) of this region of the human major histocompatibility complex. These YACs extended from the region centromeric to HLA-E to the region telomeric to HLA-F. In addition to the recognized class I genes and pseudogenes and the anonymous non-class-I genes described recently by us and others, 20 additional anonymous cDNA clones were identified from this 1-Mb region. We also identified a long repetitive DNA element in the region between HLA-B and HLA-E. Homologues of this element were located at several sites in the human genome outside of the HLA complex. The portion of the HLA class I region represented by these YACs shows an average gene density as high as the class II and class III regions. Thus, the high gene density portion of the HLA complex is extended to more than 3 Mb.     

Weighted Coherence: A More Effective Measure Than Average Coherence

In this study, we evaluated the effectiveness of the statistic, Weighted Coherence in relation to the average or mean coherence in a particular frequency band after cross-spectral analysis. In time domain, correlation coefficient explains the relationship between two variables of interest, and a similar statistic in frequency domain using cross-spectral analysis is referred to as coherence, which is equivalent to the squared correlation coefficient and ranges from zero to unity. In this study, we show that weighted coherence is much more sensitive to various challenges within the same subject and also may be a more sensitive indicator of group differences in different frequency bands. Our data on normal subjects and patients with panic disorder during supine and standing postures during normal breathing, and also at different breathing rates throw new light on the sensitivity of this previously described novel index to quantify coherence between two related time series such as beat-to-beat heart rate and QT interval.     

Prevalence of double diabetes in youth onset diabetes patients from east Delhi and neighboring NCR region

Background

It is being increasingly reported that some of the youth onset diabetes patients cannot be classified clearly as type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) based on usual criteria and the term double diabetes (DD) coined for these cases.

New Insights into Understanding the Mechanisms,Pathogenesis, and Management of Malignant Mesotheliomas

Malignant mesothelioma (MM) is a relatively rare but devastating tumor that is increasing worldwide. Yet, because of difficulties in early diagnosis and resistance to conventional therapies, MM remains a challenge for pathologists and clinicians to treat. In recent years, much has been revealed regarding the mechanisms of interactions of pathogenic fibers with mesothelial cells, crucial signaling pathways, and genetic and epigenetic events that may occur during the pathogenesis of these unusual, pleiomorphic tumors. These observations support a scenario whereby mesothelial cells undergo a series of chronic injury, inflammation, and proliferation in the long latency period of MM development that may be perpetuated by durable fibers, the tumor microenvironment, and inflammatory stimuli. One culprit in sustained inflammation is the activated inflammasome, a component of macrophages or mesothelial cells that leads to production of chemotactic, growth-promoting, and angiogenic cytokines. This information has been vital to designing novel therapeutic approaches for patients with MM that focus on immunotherapy, targeting growth factor receptors and pathways, overcoming resistance to apoptosis, and modifying epigenetic changes.CME Accreditation Statement: This activity (“ASIP 2013 AJP CME Program in Pathogenesis”) has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Society for Clinical Pathology (ASCP) and the American Society for Investigative Pathology (ASIP). ASCP is accredited by the ACCME to provide continuing medical education for physicians.The ASCP designates this journal-based CME activity (“ASIP 2013 AJP CME Program in Pathogenesis”) for a maximum of 48 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.CME Disclosures: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.Malignant mesotheliomas (MMs), among the most aggressive tumors, arise most often from the mesothelial cells that line the pleura, peritoneum, and, occasionally, the pericardium. Because of the multifaceted properties of mesothelium that maintain a protective barrier but also produce components of the extracellular matrix, hyaluronan and other lubricants, chemokines and cytokines, and fibrinolytic and procoagulant factors, understanding its complex biology is a challenge. The intermediate filament pattern of mesothelial cells, suggesting an epithelial–mesodermal hybrid morphology, and their several patterns of differentiation during the neoplastic process suggest their transformation to malignancy is complicated and raises the question of whether one is studying a single tumor type or multiple subgroups of tumors.MMs are most commonly attributed to occupational exposures to asbestos, a regulatory term for a group of fibrous silicates that occur as needle-like amphiboles (crocidolite, amosite tremolite, anthophyllite, and antigorite) or curly serpentine (chrysotile) fibers. Although each of these fibers has its own distinctive properties, the fibrous nature and biopersistance of these inhaled fibers may be key to carcinogenic events that occur during the long latency periods (mean, 30 to 45 years) of most MMs. Most intensely investigated are chrysotile, the most commonly used type of asbestos historically (>90% use worldwide), and crocidolite, the asbestos type associated most often with MMs in humans^1,2 (Figures 1 and 2). The morphology of crocidolite asbestos is similar to nonasbestos fibers of erionite or Libby amphibole, other naturally occurring minerals associated with the development of MMs.^5,6 However, 20% to 25% of individuals with MM have no documented exposure to asbestos or other fibers, suggesting familial susceptibility (sporadic or idiopathic MM), unknown exposure to in-place or naturally occurring asbestos, or other causative agents, such as chemicals, radiation, and viruses.⁷Open in a separate windowFigure 1Properties of chrysotile (white) asbestos. A: Image of bundle of curly chrysotile fibers before processing. B: Scanning electron micrograph of chrysotile fibers (arrows) causing deformation of red blood cells. Chrysotile is positively charged, hemolytic, and cytolytic, primarily due to its magnesium content. Leaching of magnesium renders chrysotile less toxic and also results in chrysotile fiber dissolution over time. C: Scanning electron micrograph of interaction of long chrysotile fiber with the respiratory epithelium of the alveolar duct junction after inhalation by rats. Arrowheads show points of contact with and between epithelial cells. Subsequent penetration into and between cells leads to fiber deposition in the lung interstitum and access to the visceral pleura and pleural space. D: Polarized microscopy showing chrysotile fibers and fibrils.Photomicrograph is a courtesy of Lee Poye (J3 Resources, Inc., Houston, TX) Original magnification, ×100.Open in a separate windowFigure 2Properties of crocidolite, or blue, asbestos. A: Riebeckito ore showing veins of crocidolite asbestos fibers (arrow) before processing. B: Scanning electron micrograph showing morphology of needle-like fibers. C: Early penetration of a crocidolite fiber into the differentiated tracheobronchial epithelium in tracheal organ culture. D: Growth of metaplastic cells over long fibers of crocidolite observed at 1 month in this model.³ These events have not been captured in the pleura in animal inhalation models or in clinical specimens in humans, but mesothelial cells undergo proliferation, as measured by cell counts, or immunochemical markers have been observed in response to crocidolite asbestos in vitro and after inhalation by rats.⁴Because asbestos fibers neither appear to be metabolized nor directly interact with DNA, they are unlike most chemical carcinogens. The sensitivity of human mesothelial cells to fibers of high aspect (length to diameter) ratio is also perplexing, as are the phenomena governing fiber transport to the parietal pleura where most MMs are thought to develop. Although much insight exists on understanding how fibers (particularly high iron-containing amphibole asbestos types) generate reactive oxygen and nitrogen species to induce inflammation and cell signaling pathways important in proliferation and transformation, how these cellular events converge in the pathogenesis of MM remains enigmatic. This review amalgamates current observations in the field and their implications in strategies to prevent and manage MMs in patients.     

Molecular identification of enteroviruses associated with aseptic meningitis in children from India

We identified and characterized enteroviruses associated with aseptic meningitis in children between April 2009 and March 2010. Enterovirus RNA was detected in 51 (45.5 %) of 112 CSF samples. Molecular typing by RT-PCR and sequencing of a partial VP1 region revealed the predominance of echovirus (ECV) 32 (n = 20), followed by ECV 11 (n = 10), ECV 13 and ECV 14 (n = 5 each), coxsackievirus (CV) B3 and CV B6 (n = 3 each), CV A2, CV A10 and ECV 30 (n = 1 each). Phylogenetic analysis of ECV 32 showed 0 to 4 % sequence divergence among strains of the present study and 20-23 % from the prototype Puerto Rico strain at the nucleotide level. This is the first report of ECV 32 associated with an aseptic meningitis epidemic and identification of seven different enterovirus serotypes (CV A2, CV A10, CV B3, CV B6, ECV 13, ECV 14 and ECV 32) in meningitis cases from India.     

Activation of defense response in common bean against stem rot disease triggered by Trichoderma erinaceum and Trichoderma viride

White mold and stem rot is a common disease of Phaseolus vulgaris caused by Sclerotinia sclerotiorum. Biological control is a promising alternative for the control of this disease. In the present study, two Trichoderma spp., T. erinaceum and T. viride, and the consortium of both were evaluated as biocontrol agents against sclerotinia stem rot disease. The results revealed that T. erinaceum (NAIMCC-F-02171) and T. viride (NAIMCC-F-02500) when applied alone, significantly suppressed the infection rate of S. sclerotiorum and increased the rate of survival of plants by 74.5%. On the contrary, the combination of both the Trichoderma spp. was found to be more effective in reducing stem rot by 57.2% and increasing the survival of plants by 87.5% when compared to the individual Trichoderma applications. Further, the exogenous supplementation of Trichoderma activated antioxidative machineries, such as peroxidase, polyphenol oxidase, superoxide dismutase, catalase, and ascorbic acid in the plant. Besides, hydrogen peroxide and superoxide-free radical accumulation were also found to be reduced when T. erinaceum and T. viride were used either individually or in combination under the pathogen-challenged condition. Additionally, the photopigments in the bioprimed plants were markedly increased. Moreover, the combined inoculation of the two isolates yielded the highest records of growth parameters (root weight, shoot length, and leaf weight) compared with individual inoculation. Therefore, based on the above results, it was concluded that the combination of T. erinaceum and T. viride can be effectively used as an alternative to control white mold and stem rot caused by S. sclerotiorum.     

Dental extraction in a patient with undiagnosed Von Willebrand’s Disease: a case report

Dental extractions are a common part of general dental practice. While dentists routinely screen for medical contraindications during the preoperative assessment, undiagnosed coagulopathies have the potential to severely complicate a seemingly routine extraction. We report a case of surgical removal of a mandibular third molar in a patient with undiagnosed Von Willebrand Disease.     

Evaluation of Antiviral Activities of Four Local Malaysian Phyllanthus Species against Herpes Simplex Viruses and Possible Antiviral Target

Nucleoside analogues such as acyclovir are effective antiviral drugs against herpes simplex virus infections since its introduction. However, with the emergence of acyclovir-resistant HSV strains particularly in immunocompromised patients, there is a need to develop an alternative antiherpetic drug and plants could be the potential lead. In this study, the antiviral activity of the aqueous extract of four Phyllanthus species were evaluated against herpes simplex virus type-1 (HSV-1) and HSV-2 in Vero cells by quantitative PCR. The protein expressions of untreated and treated infected Vero cells were studied by 2D-gel electrophoresis and Western blot. This is the first study that reported the antiviral activity of P. watsonii. P. urinaria was shown to demonstrate the strongest antiviral activity against HSV-1 and HSV-2, with SI >33.6. Time-of-addition studies suggested that the extract may act against the early infection stage and the replication stage. Protein expression studies indicated that cellular proteins that are involved in maintaining cytoskeletal structure could be potential target for development of antiviral drugs. Preliminary findings indicated that P. urinaria demonstrated potent inhibitory activity against HSV. Hence, further studies such as in vivo evaluation are required for the development of effective antiherpetic drug.