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Streptozotocin-Induced Diabetes: Induction, Mechanism(s), and Dose Dependency
Published in John H. McNeill, Experimental Models of Diabetes, 2018
Brian Rodrigues, Patrick Poucheret, Mary L. Battell, John H. McNeill
In addition to the above effects of STZ on β-cells, this agent has also been used to induce diabetes with multiple low doses.38 After multiple low-dose injection of STZ, islet degeneration due to direct STZ toxicity has been suggested to initiate an inflammatory response whereby mononuclear cells migrate from the bloodstream to the tissue, where they differentiate into macrophages.39 These cells phagocytose the pancreatic β-cells, thereby releasing cytochemical mediators.40 Subsequently, lymphocytic infiltration occurs.41
Congenital Hypothyroidism Associated with Thyrotropin Unresponsiveness
Published in Geraldo Medeiros-Neto, John Bruton Stanbury, Inherited Disorders of the Thyroid System, 2019
Geraldo Medeiros-Neto, John Bruton Stanbury
Another subject with impaired thyroidal response to TSH stimulation was reported by Medeiros-Neto et al.3 The patient was a 19-year-old male with severely retarded development (Figure 4). The parents were first cousins and another sibling had clinical hypothyroidism. The thyroid gland was not enlarged and was normal in shape on thyroid scan. Bone age was 7 years. The biopsy specimen revealed a microfollicular pattern with scant colloid. There was no lymphocytic infiltration anywhere in the specimen (Figure 5). Search for thyroid autoantibodies was repeatedly negative. Exogenous bovine TSH failed to increase iodide uptake by the thyroid (Table 2). Studies on the biopsy specimen revealed low iodide trapping by the thyroid slices that increased slightly after TSH stimulation. cAMP per milligram of thyroid tissue was also measured in control flasks and after bovine TSH was added to the medium (Table 2). Also, normal thyroid tissue slices were submitted to stimulation by 0.2 ml of the patient’s serum (with a measured TSH concentration of 192 μU/ml). The patient’s thyroid slices had a significantly lower mean basal concentration of cAMP and no change in cAMP concentration was observed after TSH. Moreover, the patient’s serum with a high level of endogenous TSH was able to induce a significant increase in the cAMP concentration above basal level in normal thyroid slices. There was no biochemical or immunological evidence for thyroglobulin in the soluble extract of the thyroid. It was postulated that the fundamental defect in this patient was an impaired generation of cAMP due to a defective interaction of biologically active thyrotropin with its specific membranal receptor.
Therapeutic potential of human serum albumin nanoparticles encapsulated actinonin in murine model of lung adenocarcinoma
Published in Drug Delivery, 2022
Priyanca Ahlawat, Kanika Phutela, Amanjit Bal, Navneet Singh, Sadhna Sharma
The histological observations revealed control lung with normal lung parenchymal cells. In tumor bearing mice lungs, the tumor nodules had presence of tumor cells in papillary and glandular pattern which represents classical morphological features of adenocarcinoma (Figure 5(B)b). The treatment groups with tumor nodules had few pink regions representing the apoptotic areas (Figure 5(B)c, yellow arrow) and also showed lymphocytic infiltration (Figure 5(B)c&e, black arrows). The lung tissue in certain areas with undefined carcinogenic features was seen to have apoptotic regions and minimal lymphocytic infiltration (Figure 5(B)d, black arrows). Also, no systemic toxicity was observed upon therapy as seen in liver, kidney and spleen tissues (Figure 5(B) e–g). The tumor lesions identified grossly were confirmed to have tumorigenic origins by flow cytometric identification of EpCAM+ and CD45+ cell populations in the excised tumor lesions single cell suspensions. EpCAM is an epithelial cell marker essential to identify adenocarcinoma whereas CD45 is a lymphocytic marker and can indicate an inflammatory background induced due to urethane. The excised tumors displayed EpCAM+ cells population (29.6%) and CD45+ cells population (44.8%) (Figure 5(C)a,b). This demonstrated that the sample had lymphocytic infiltration as seen from the histological examinations. This screening helped in identifying that the gross tumor nodule on the lung tissue was of cancerous nature and therefore was used further for cytometric analysis.
Biological mechanisms of ectopic lymphoid structure formation and their pathophysiological significance
Published in International Reviews of Immunology, 2021
Tatjana Marinkovic, Dragan Marinkovic
Unexpectedly, research studies based on models of renal and cardiac allografts, described that ELS also may promote allograft tolerance and graft function [109,110]. Even more, lymphocytic infiltration was observed in two cases of long term surviving human kidney grafts [111]. This surprising finding opened a question regarding the role of ELS in induction of tolerance. It seems that rejection or survival of a transplanted organ depends on the balance between graft destructive alloreactive T cells and graft protective regulatory T cells [112]. The explanation of mechanisms that correlate tertiary lymphoid organs in renal allografts with donor-specific tolerance rather than rejection includes the postulation that ELS may be involved in promotion of regulatory B and T cells [109,110]. Similar mechanism was already described in cancer, with the evidences that Treg cells in tumor-associated ELS can inhibit endogenous immune responses against tumors [104].
DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles
Published in OncoImmunology, 2021
Sepehr Safaei, Malte Mohme, Judith Niesen, Ulrich Schüller, Michael Bockmayr
To get a more detailed insight into the distribution of TILs in different brain tumor subgroups, we applied our method to the validation data of LGG, GBM, MB, ATRT and EPN. Methylation-based diagnoses were computed with the Heidelberg Brain Tumor classifier.25 As WHO grade III and IV tumors were present in the LGG and the GBM dataset, both datasets were combined to a glioma dataset. The differences in TIL scores between the 6 glioma entities were highly significant (Figure 5b, p = 1.6e-36). Estimated infiltration was lowest in IDH (Isocitrate dehydrogenase) mutated oligodendroglioma and in IDH mutated astrocytoma and highest in mesenchymal glioblastoma. For medulloblastoma, although statistically significantly different between molecular subgroups (p = 1.7e-49), the TIL score was overall low. The lowest number was found in Group 4 medulloblastoma and the largest number in Group 3 (Figure 5c). ATRTs showed prominent lymphocytic infiltration. The ATRT MYC subgroup had significantly more TILs than TYR (intermediate) and SHH (lowest) ATRT (p = 0.00012, Figure 5d). The TIL scores were significantly different between ependymoma subgroups (p = 4.4e-0.8, Figure 5e) with the lowest scores in the YAP and the PF B subgroup and the highest scores in the PF A and the RELA subgroup.