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इम्यूनोकैमिस्ट्री और इम्यूनोपैथोलॉजी

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आयतन 2, मुद्दा 1 (2016)

शोध आलेख

Analysis of the Relationship between the Levels of Carcinoembryonic Antigen and Lactate Dehydrogenase, and the Neutrophil/Lymphocyte Ratio in Colorectal Cancer

Sebahattin Celik, M Eyüp Yılmaz and Ethem Bilgiç

Background: Tumor markers and inflammatory markers by themselves are associated with prognostic and clinicopathological factors in colorectal cancers. The objective of this study was to explore the relationship between the levels of carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH), and the neutrophil-lymphocyte ratio (NLR) in colorectal cancer.

Methods: We conducted a retrospective clinical study of 145 patients diagnosed with colon or rectal cancer between January 1, 2013 and December 30, 2014 in two hospitals in Turkey. Only patients whose records contained demographic information (age, gender), pathology reports, and radiology reports were included in the study. The levels of CEA and LDH as well as the LNR were noted.

Results: Of the 145 patients, 87 (60%) patients had colon cancer and 58 (40%) patients had rectal cancer. Over half of all the patients (55.8%) had stage 3 or stage 4 cancer. The median levels of CEA and LDH were in the normal clinical range while the NLR was 2.9. In both colon and rectal tumors, there was a weak positive but statistically significant relationship between CEA, LDH and NLR (r<25 and p<0.05 in all comparisons). In analyzing the correlation in terms of tumor stage, there was no good correlation. The strongest relationship (r=0.424, p=0.022) was between CEA and LDH in stage 1 tumors. In all other tumor stages there was no correlation.

Conclusion: In colorectal cancers; CEA, LDH and NLR may be important individually, but no relation appears between them.

शोध आलेख

NLRP10 A Potential Contributor to the Anti-Inflammatory Effects of IVIg in Sepsis

Lionel Loubaki, Dominique Chabot and Renée Bazin

Intravenous immunoglobulin (IVIg) is used to treat a number of inflammatory diseases including sepsis. The objective of this study was to evaluate whether NLRP10, postulated as a negative regulator of inflammasome activation, can play a role in the anti-inflammatory effects observed in the treatment of severe sepsis with IVIg. Human peripheral blood monocytes were isolated and treated either with LPS or IVIg, or alternatively treated first with LPS followed by addition of IVIg. The induction of IL-1β and IL-18 was used as an index of inflammasome activation. Treatment of resting monocytes with IVIg resulted in a significant increase in the expression of NLRP10. LPS but not IVIg resulted in a significant increase in both IL-1β and IL-18 protein release, consistent with inflammasome activation. Furthermore, addition of IVIg to LPS-treated monocytes resulted in a significant increase in the expression of NLRP10 which was associated with a complete inhibition of both IL-1β and IL-18 increased expression. These data suggest that the IVIg-mediated induction of NLRP10 expression in monocytes contributes to the control of inflammation during sepsis and thus highlight a complementary mechanism by which IVIg exerts their anti-inflammatory effects in sepsis.

शोध आलेख

Role of the CD62L Expression Pathway in the IVIg Inhibition of Cytotoxic T Cell Responses

Dominique Chabot, Patrick Trépanier, Cassandra Ringuette-Goulet, Lionel Loubaki and Renée Bazin

Intravenous immunoglobulin (IVIg) is successfully used in the treatment of a number of immune-mediated disorders, including diseases in which self-reactive cytotoxic CD8+ T lymphocytes (CTLs) play an important pathological role. However, the exact molecular and cellular mechanisms underlying its effects on the cytotoxic response remain undefined. Using a mouse model of ovalbumin (OVA) immunization, we recently showed that IVIg treatment decreases the in vivo generation of OVA-specific CD8+ T cells, as well as the proportion of CTLs expressing the extracellular cytotoxic marker CD107a. In the present work, we demonstrate that during the course of an active immune response in mice, IVIg treatment is associated with the presence of splenic CD8+ T cells expressing high levels of CD62L and by an increased plasma concentration of soluble CD62L. Because cell surface expression of CD62L negatively correlates with the cytotoxic activity of CD8+ T cells and that soluble CD62L exhibits anti-inflammatory effects, we herein propose that the CD62L expression pathway plays a key role in the therapeutic effects of IVIg in CD8-mediated autoimmune and inflammatory disorders.

मामला का बिबरानी

A Rare Clinical Presentation of Diabetes Mellitus

Vivek Batra and Gurshawn Singh

This case report highlights a rare presentation of new-onset diabetes. Hemichorea- hemiballismus due to nonketotic hyperglycemia is a rare disorder, which comprises of unilateral, periodic choreiform movement of the extremities in the setting of hyperglycemia without evidence of ketoacidosis. Radiographically, there is hyperdensity in the basal ganglia but no evidence of bleeding or mass effect on CT scan of the brain. MRI of the brain shows increased T1-signal intensity in the contralateral putamen. The immunopathology is hyperglycemia mediated, which causes ischemic excitation of GABAergic-neurons in the basal ganglia. This leads to excessive inhibition of subthalamic nuclei and excitatory cortical input causing involuntary movement unilaterally. The mainstay treatment of this condition is insulin therapy, and the movement disorder disappears once glycemic control is achieved.

शोध आलेख

Levels of Interleukin-17 and Interleukin-23 in Patients with Systemic Lupus Erythematosus (SLE) in Trinidad and Tobago

Alisa Nobee, Angel Justiz-Vaillant, Patrick E Akpaka and Peter Poon-King

Serum interleukin (IL)-17 and IL-23 and their association with systemic lupus erythematosus (SLE) is not well understood. A prospective cross sectional and observational study was done using twenty eight (28) SLE patients and fourteen (14) non SLE control subjects. Blood samples were taken to delineate the presence of IL-17 and IL-23 using ELISA among patients of the Rheumatology out-patient clinic at the San Fernando General Hospital, Trinidad and Tobago. The Systemic lupus erythematosus disease activity index (SLEDAI) 2000 score was used for evaluation of activity of the disease. It was found that of all the SLE patients 13 patients (47%) were of Afro-Trinidadian descent, 11 patients (39%) were of Indo-Trinidadian descent and 4 patients (14%) were of mixed descent. The majority of patients were within the 31-35 year age group. Serum IL-17 and IL-23 levels were greater in SLE patients compared to healthy subjects and their levels showed a positive correlation to SLEDAI score. However further experiments are needed to elucidate the role of IL-17 and IL-23 in SLE patients from Trinidad and Tobago.

शोध आलेख

Improved Immunohistochemical Detection of Type 1 Insulin-Like Growth Factor Receptor in Human Tumors

Tamara Aleksic, Andrew Ross Worrall, Clare Verrill, Helen Turley, Leticia Campo and Valentine M Macaulay

Background: Insulin-like growth factors (IGFs) are known to play important roles in cancer biology, prompting evaluation of drugs targeting type 1 IGF receptor (IGF-1R). However, there is considerable lack of consensus in immunohistochemical (IHC) studies of IGF-1R in human tumors, confounding attempts to assess the predictive and prognostic significance of IGF-1R expression and subcellular localization. Likely sources of variation include use of different IGF-1R polyclonal antibodies and methods for IHC. Here, we aimed to develop a robust IGF-1R IHC protocol using a monoclonal antibody, suitable for use in formalin-fixed paraffin-embedded (FFPE) tissues.
Methods: Using controls including samples of FFPE tissues and tumor cells of defined IGF-1R expression, we used IHC and western blotting to compare polyclonal antibody #3027 with monoclonals #9750 and #14534 (Cell Signaling Technology).
Results: Compared with #3027, the monoclonals exhibited superior discrimination between IGF-1R-high and IGF-1R-deficient cells in manual IHC, signal generated by #9750 reflecting differences in IGF-1R expression detected by western blotting. In tissues, IGF-1R detected by #14534 was predominantly plasma membrane-associated, while #9750 detected IGF-1R in the plasma membranes, cytoplasm and nucleus of prostate and renal cancers, recapitulating appearances we described using previous lots of #3027, and reflecting subcellular localizations reported using other techniques. Use of #9750 and #14534 in an autostainer showed adequate differentiation of high vs low IGF-1R cells, but did not recapitulate appearances of manually-stained tissues. We provide a detailed protocol for the preferred manual method using #9750.
Conclusion: Standardization of IGF-1R IHC will promote understanding of the role of IGF-1R in tumor biology, and its potential as a candidate prognostic and predictive biomarker.

शोध आलेख

Study Hydrophobicity and Antigenicity of Cytochrome C Oxidase Subunit II from D. medinensis: New Prototype of Synthetic Vaccine Development

Sonu Mishra and Virendra S Gomase

Cytochrome c oxidase subunit II, also known as cytochrome c oxidase polypeptide II which is an oligomeric enzyme. In this study Cytochrome c oxidase subunit 2 (mitochondrion) protein has been used to investigate its role in antigenicity. Cytochrome c oxidase subunit 2 protein sequences (230 aa protein) is analyzed through different types B- cell epitope prediction methods. We found that the region of maximal hydrophilicity is likely to be an antigenic site, having hydrophobic characteristics, because the terminal regions of antigen protein is solvent accessible and unstructured, antibodies against those regions are also likely to recognize the native protein. It was seen that an antigen protein is hydrophobic in nature and contains segments of low complexity and high-predicted flexibility. The predicted antigenic protein segments of Cytochrome c oxidase subunit 2 can take active part in the host immune reactions. In future study the predicted antigenic protein Cytochrome c oxidase subunit 2 fragments can be used in the investigation of MHC molecules binding and it can be the first bottlenecks in vaccine design.

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