Focal neuroendocrine carcinoma mixed with adenocarcinoma of the gallbladder with aggressive lymph node metastasis in a patient who did not meet the mixed neuroendocrine–non-neuroendocrine neoplasm criteria

A 70-year-old Japanese woman who was treated for interstitial pneumonia (IP) with steroid therapy developed cholecystitis. A serial computed-tomography (CT) imaging showed irregular thickness of the fundus wall of the gallbladder and two rapidly enlarged lymph nodes (LNs): number (no.) 12 and no. 8a. Positron-emission tomography-computed tomography (PET-CT) scan showed an abnormal uptake at the site of the gallbladder tumor and those LNs. We subsequently performed open radical cholecystectomy and LN dissection of the no. 12 and 8a LNs, following complete remission of IP. The histology showed gallbladder adenocarcinoma, with a single focus of neuroendocrine carcinoma (NEC) component of less than 30%; Ki-67 index > 80%, synaptophysin (Syn) (+), chromogranin A (CgA) (+), and clusters of differentiation (CD) 56 (+) (T2bN1M0, Stage IIIB). LN no. 8a was diffusely metastatic with NEC components. LN no. 12c, which was adjacent to the cystic duct, revealed necrosis without apparent tumor cells, but was highly suspicious for tumor necrosis. The final diagnosis was adenocarcinoma of the gallbladder with focal NEC (< 30%), which did not meet the criteria for mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN). Postoperatively, she completed 4 cycles of adjuvant chemotherapy for NEC (Cisplatin plus Etoposide), and no recurrence was observed after 12 months.

Phage-Phenotype Imaging of Myeloma Plasma Cells by Phage Display

Multiple myeloma (MM) is a malignant disease based on differentiated plasma cells (PCs) in the bone marrow (BM). Flow cytometry and fluorescence microscopy, used to identify a large combination of clusters of differentiation (CDs), are applied for MM immunophenotyping. However, due to the heterogeneous MM immunophenotypes, more antibody panels are necessary for a preliminary diagnosis and for the monitoring of minimal residual disease (MRD). In this study, we evaluated the use of phage clones as probes for the identification of several PCs immunophenotypes from MM patients. First, A 9-mer M13-pVIII phage display library was screened against an MM.1 cells line to identify peptides that selectively recognize MM.1 cells. Then, the most representative phage clones, with amino acid sequences of foreign peptides closer to the consensus, were labelled with isothiocyanate of fluorescein (FITC) and were used to obtain a fluorescent signal on cells in ex-vivo samples by fluorescence microscopy. Selected phage clones were able to discriminate different MM immunophenotypes from patients related to CD45, CD38, CD56, and CD138. Our results highlight the possibility of using a phage-fluorescence probe for the simultaneous examination of the presence/absence of CDs associated with disease usually detected by combination of anti-CD antibodies. The design of a multi-phage imaging panel could represent a highly sensitive approach for the rapid detection of immunophenotype subtypes and the subsequent characterization of patient disease status.

Tissue Harvesting Site Effect on the Canine Adipose Stromal Vascular Fraction Quantity and Quality

Mesenchymal stem cells (MSCs) constitute a great promise for regenerative therapy, but these cells are difficultly recovered in large amounts. A potent alternative is the stromal vascular fraction (SVF), non-cultured MSCs, separated from adipose tissue (AT). We aim to evaluate AT harvesting site effect on the SVF cells’ quantity and quality in dogs. Subcutaneous abdominal fat, falciform ligament and peri-ovarian fat were sampled. After SVF isolation, the trypan blue exclusion test and a hemocytometer were used to assess the cell viability and cellular yield. SVF cells were labeled for four surface antigenic markers, clusters of differentiation CD90, CD44, CD29, and CD45, and then examined by flow cytometry. Semi-quantitative RT-PCR was used to evaluate the gene expression of the former markers in addition to OCT-4 and CD34. SVF cells in the peri-ovarian AT recorded the highest viability% (99.63 ± 0.2%), as well as a significantly higher cellular yield (36.87 ± 19.6 × 106 viable cells/gm fat, p < 0.001) and a higher expression of adipose-derived mesenchymal stem cells AD-MSCs surface markers than that of other sites. SVF cells from the peri-ovarian site revealed a higher expression of MSC markers (CD90, CD44, and CD29) and OCT-4 compared to the other sites, with weak CD45 and CD34 expressions. The positive OCT-4 expression demonstrated the pluripotency of SVF cells isolated from different sites. To conclude, the harvesting site is a strong determinant of SVF cells’ quantity and quality, and the peri-ovarian site could be the best AT sampling site in dogs.

CD36 and CD97 in Pancreatic Cancer versus Other Malignancies

Starting from the recent identification of CD36 and CD97 as a novel marker combination of fibroblast quiescence in lung during fibrosis, we aimed to survey the literature in search for facts about the separate (or concomitant) expression of clusters of differentiation CD36 and CD97 in either tumor- or pancreatic-cancer-associated cells. Here, we provide an account of the current knowledge on the diversity of the cellular functions of CD36 and CD97 and explore their potential (common) contributions to key cellular events in oncogenesis or metastasis development. Emphasis is placed on quiescence as an underexplored mechanism and/or potential target in therapy. Furthermore, we discuss intricate signaling mechanisms and networks involving CD36 and CD97 that may regulate different subpopulations of tumor-associated cells, such as cancer-associated fibroblasts, adipocyte-associated fibroblasts, tumor-associated macrophages, or neutrophils, during aggressive pancreatic cancer. The coexistence of quiescence and activated states in cancer-associated cell subtypes during pancreatic cancer should be better documented, in different histological forms. Remodeling of the local microenvironment may also change the balance between growth and dormant state. Taking advantage of the reported data in different other tissue types, we explore the possibility to induce quiescence (similar to that observed in normal cells), as a therapeutic option to delay the currently observed clinical outcome.

The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders

: The bidirectional communication between neurons and microglia is fundamental for the proper functioning of the central nervous system (CNS). Chemokines and clusters of differentiation (CD) along with their receptors represent ligand-receptor signalling that is uniquely important for neuron – microglia communication. Among these molecules, CX3CL1 (fractalkine) and CD200 (OX-2 membrane glycoprotein) come to the fore because of their cell-type-specific localization. They are principally expressed by neurons when their receptors, CX3CR1 and CD200R, respectively, are predominantly present on the microglia, resulting in the specific axis which maintains the CNS homeostasis. Disruptions to this balance are suggested as contributors or even the basis for many neurological diseases. : In this review, we discuss the roles of CX3CL1, CD200 and their receptors in both physiological and pathological processes within the CNS. We want to underline the critical involvement of these molecules in controlling neuron – microglia communication, noting that dysfunctions in their interactions constitute a key factor in severe neurological diseases, such as schizophrenia, depression and neurodegeneration-based conditions.

THE OUTCOME OF CEREBRAL PATHOLOGY BY THE END OF THE FIRST YEAR OF LIFE IN NEWBORN BABIES WITH CYTOMEGALOVIRUS INFECTION

Objective: to study costimulatory molecules (CD28, CD40) on lymphocytes of the peripheral blood in newborn babies with CMVI and to determine prognostic indices of the cerebral pathology outcome by the end of the first year of life.We examined 114 children at the age of three months, who had CMVI during neonatal period. In 37 children neurological symptoms remained by the end of the first year of life. At 37 children the neurologic symptomatology by the end of the first year of life remained: delay of psychomotor development (44.8%), deafness (5.9%), epilepsy (11.9%), spastic tetraparesis (32.2%) blindness (13.4%). At 77 children was absent neurologic symptomatology by the end of the first year of life.A control group was comprised of 15 healthy newborns. The content of lymphocytes, expressing CD28, CD40, CD3+, CD4+, CD28+, CD20+, was determined using laser flow cytofluorometer “Beckman COULTER” Epics XL II (USA) by means of monoclonal antibodies to the clusters of differentiation CD3+, CD20+, CD4+, CD28+, CD40+ of IMMUNOTECH Company (France).The analysis of multidimentional nonlinear dependencies was performed using PolyAnalist 3.5. Pro package. The formula of the forecast of preservation of neurologic symptomatology is calculated.((CD3-CD28+ * 0.074) + CD4+ * (-0.182) + (CD3+CD28- * 0.035) + CD40 * (-0.2862) + CD3 * 0.1062) + + (CD28 * 0.1952)) - 0.4588.If the result of the calculation according to the formula is > 0.39, than a child will have brain damages by the end of the first year of life. Sensitivity - 71.43%, specificity - 88.89%. The likelihood ratio of the positive result is 13.5.The determination of CD3+T-lymphocytes, lymphocytes, expressing CD28 in the total population, T-lymphocytes without the costimulatory marker CD28 (CD3+CD28-) and also B-lymphocytes, expressing CD40 on their surface, is significant for the prognosis of neurological symptomatology preservation by the end of the first year of life.

Labels of aberrant Clusters of Differentiation gene expression in a compendium of systemic lupus erythematosus patients

BackgroundThis author manuscript serves as an extended annotation of gene expression for all known clusters of differentiation (CD) within a compendium of systemic lupus erythematosus (SLE) patients. The overarching goal for this line of research is to enrich the perspective of the CD transcriptome with upstream gene expression features.

SOME IMMUNE FACTORS AND HORMONES DETERMINED IN FEMALE ALBINO RATS INDUCED WITH INFERTILITY AND ADMINISTERED WITH ANTHOCLIESTA VOGELII

Anthocleista vogelii Planch, phyto-constituents was evaluated and the plant leave extracts investigated on the claims of the traditional medicine practitioners of its usage as fertility enhancer in females. Ethanolic extract of Anthocleista vogelii were administered orally for 14 days to female albino rats placed in different groups. First, temporary infertility was induced with Micronor (norethisterone) or Nacetylcysteine (NAC) given orally to some rats, for seven (7) days prior to other treatment. The rats were sacrificed after the completion of extract administration. The absolute counts of clusters of differentiation CD4+ and CD8+ was performed on the blood samples using the Becton Dickinson’s (BD) FACS Count Automated technique. Hormonal analysis was performed on sera obtained from the experimental animals using commercial standard enzyme-linked immunosorbent assay kit. The extract was found to possess Anthraquinones, Terpenoids, Flavonoids, Saponins, Alkaloids, Phenols and Phytosterols . The obtained results of the test group compared with control showed a statistically significant decrease (P<0.05) in CD4+ and CD8+ counts cells and Prolactin, testosterone respectively. The results showed a significant increase of estradiol, leutinizing hormone, in the female rats in the control group compared to extract treated group. The result also suggested that Anthocleista vogelii may have a role in creating the environment required for enhancing pregnancy by decreasing ratio of CD4+ and CD8+ linked Th1 andTh2 cytokines production activation. Estradiol, luetinising hormone, concentration therefore support the claims on the traditional use of Anthocliesta vogelii that it enhance fertility in female.

Immunophenotyping: Application to Safety Assessment

A continuing education course entitled “What You Always Wanted to Know About Immunotoxicology in Pharmaceutical Development…But Were Afraid to Ask” was offered at the Society of Toxicologic Pathology (STP) 36th annual symposium in Montreal. This article summarizes some key points made during the presentation dedicated to immunophenotyping. It describes how clusters of differentiation (CDs) are well-defined antigens used to characterize cell subsets, and how lymphocyte subsets in humans and different rodent and nonrodent species can be defined by detection of various combinations of CDs. It provides an overview of immunophenotyping study design considerations and applications to safety assessment.