Clinicopathologic Features of Gastrointestinal Tract Langerhans Cell Histiocytosis.

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months.

Density of Biopsy Sampling Required to Ensure Accurate Histological Assessment of Inflammation in Active Ulcerative Colitis.

Background: Histological response to treatment is an important outcome in patients with ulcerative colitis (UC). The accuracy of biopsy-based measurements of inflammation may be limited by error imposed by natural microscopic heterogeneity on the scale of individual biopsies. We determined the magnitude of this error, its histological correlates, and the density of biopsy sampling within mucosal regions of interest required to meet specified benchmarks for accuracy.

The Long Noncoding RNA Cardiac Mesoderm Enhancer-Associated Noncoding RNA (Carmn) Is a Critical Regulator of Gastrointestinal Smooth Muscle Contractile Function and Motility.

Background & Aims: Visceral smooth muscle cells (SMCs) are an integral component of the gastrointestinal (GI) tract that regulate GI motility. SMC contraction is regulated by posttranslational signaling and the state of differentiation. Impaired SMC contraction is associated with significant morbidity and mortality, but the mechanisms regulating SMC-specific contractile gene expression, including the role of long noncoding RNAs (lncRNAs), remain largely unexplored.

Aberrant p53 expression is associated with neoplastic progression in Barrett oesophagus diagnosed as indefinite for dysplasia.

The aim of this study was to investigate the role of immunohistochemical (IHC) expression of p53 and other potential clinical parameters as prognostic markers for predicting neoplastic progression in Barrett oesophagus (BE) patients diagnosed as indefinite for dysplasia (IND). The study included patients with established BE of any extent who had a diagnosis of IND accompanied by concurrent p53 immunohistochemistry (IHC) stain at the index endoscopic procedure and at least one follow-up examination between 2000 and 2021. Correlation between disease progression from IND to higher-grade dysplasia [low-grade dysplasia (LGD), high-grade dysplasia (HGD) and oesophageal adenocarcinoma (EAC)] and clinicopathological parameters were analysed.

Nodular Histiocytic/Mesothelial Hyperplasia Mimicking Mesenteric Metastasis.

Nodular histiocytic/mesothelial hyperplasia (NHMH) is a rare histologic entity, characterized by localized benign reactive proliferation of histiocytes and mesothelial cells. The presence of this rare entity poses a challenge in differential diagnosis, both in radiological findings and pathological interpretations under certain circumstances, and consequently has been misdiagnosed as malignancy. Here, we report a case of mesenteric NHMH in a patient with colonic mucinous adenocarcinoma.

Heterotopic Mesenteric Ossification With Trilineage Hematopoiesis.

Heterotopic ossification (HO) histologically refers to extraskeletal bone formation in non-ossifying tissues, most commonly noted in the extremities, buttocks, abdominal wall, and hip joints. HO developing in the mesentery (heterotopic mesenteric ossification, HMO) is very rare, with fewer than 100 cases reported in the literature. It usually occurs in adult male patients with a history of repeated abdominal trauma.

Human Intestinal Spirochetosis Incompatible With Dysplastic Adenomatous Epithelium.

Human intestinal spirochetosis (HIS) refers to the colonization of spirochetal bacteria in the human intestinal tract. HIS caused by spp. has been recognized for decades, but their pathological and clinical significance is largely unclear.

Impact of pathological response after neoadjuvant chemotherapy on adjuvant therapy decisions and patient outcomes in gastrointestinal cancers.

Background: Neoadjuvant chemotherapy (NAC) is frequently used in gastrointestinal cancers (GIC), and pathological, radiological, and tumor marker responses are assessed during and after NAC.

Aim: To evaluate the relationship between pathologic, radiologic, tumor marker responses and recurrence-free survival (RFS), overall survival (OS), adjuvant chemotherapy (AC) decisions, and the impact of changing to a different AC regimen after poor response to NAC.

Methods And Results: Medical records of GIC patients treated with NAC at Mount Sinai between 1/2012 and 12/2018 were reviewed.

Increased immature T-cells detected by flow cytometry in post chemotherapeutic patients with acute myeloid leukemia, a case report and small series study.

Detection of minimal/measurable residual disease (MRD) in bone marrow specimens by flow cytometry is widely used in patients with T cell acute lymphoblastic leukemia (T-ALL). It plays a central role in guiding treatment and assessing prognosis. However, the occurrence of a normal physiologic reactive immature T-cell population in treated bone marrow is unknown.

Colonic Adenocarcinoma at Advanced Stage in Adolescence: Report of 2 Cases.

Background: Carcinoma of colon is rare in children and adolescents. The staging criteria of the carcinoma is the same as those for adults. However, the pathogenetic background in pediatric cases is different from adults and usually involves mismatch repair gene mutations or familial polyposis syndromes.

Increased SPARC expression is associated with neoadjuvant therapy in resectable pancreatic ductal adenocarcinoma.

Secreted Protein Acid and Rich in Cysteine (SPARC) is an extracellular glycoprotein secreted by fibroblasts and osteoblasts in normal tissues. SPARC overexpression occurs in multiple tumors including pancreatic ductal adenocarcinoma (PDAC) and may predict favorable response to nab-paclitaxel. The prognostic significance of SPARC expression in PDAC is unclear - some reports indicate SPARC overexpression associates with poor outcomes and others find no correlation.

Fatal pulmonary embolism and pulmonary hemorrhage in lupus anticoagulant hypoprothrombinemia syndrome: a case report and review of literature.

: Lupus anticoagulant hypoprothrombinemia syndrome (LAHS) is a rare disorder characterized by development of lupus anticoagulant and antiprothrombin antibodies. The most common clinical manifestation is bleeding. Clinical management can be challenging due to the subtle balance between the bleeding and thrombotic tendencies.

The SmgGDS splice variant SmgGDS-558 is a key promoter of tumor growth and RhoA signaling in breast cancer.

Unlabelled: Breast cancer malignancy is promoted by the small GTPases RhoA and RhoC. SmgGDS is a guanine nucleotide exchange factor that activates RhoA and RhoC in vitro. We previously reported that two splice variants of SmgGDS, SmgGDS-607, and SmgGDS-558, have different characteristics in binding and transport of small GTPases.

Characterization of intestinal dendritic cells in murine norovirus infection.

We have shown that respiratory viral infections drive allergic disease through dendritic cells, whether gastrointestinal viruses induce allergies is not known. Norovirus infections are a major cause of gastroenteritis in humans. We used murine norovirus (MNV) to explore the effect of MNV infection on gastrointestinal conventional DCs (cDCs) and plasmacytoid DCs (pDCs).

Analysis of the CD1 antigen presenting system in humanized SCID mice.

CD1 molecules are glycoproteins that present lipids and glycolipids for recognition by T cells. CD1-dependent immune activation has been implicated in a wide range of immune responses, however, our understanding of the role of this pathway in human disease remains limited because of species differences between humans and other mammals: whereas humans express five different CD1 gene products (CD1a, CD1b, CD1c, CD1d, and CD1e), muroid rodents express only one CD1 isoform (CD1d). Here we report that immune deficient mice engrafted with human fetal thymus, liver, and CD34(+) hematopoietic stem cells develop a functional human CD1 compartment.

Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function.

Abetalipoproteinemia (ABL) is a rare Mendelian disorder of lipid metabolism due to genetic deficiency in microsomal triglyceride transfer protein (MTP). It is associated with defects in MTP-mediated lipid transfer onto apolipoprotein B (APOB) and impaired secretion of APOB-containing lipoproteins. Recently, MTP was shown to regulate the CD1 family of lipid antigen-presenting molecules, but little is known about immune function in ABL patients.

Recognition of lyso-phospholipids by human natural killer T lymphocytes.

Natural killer T (NKT) cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands.

Natural killer T-cell autoreactivity leads to a specialized activation state.

Natural killer T (NKT) cells are innate-like T cells that recognize specific microbial antigens and also display autoreactivity to self-antigens. The nature of NKT-cell autoreactive activation remains poorly understood. We show here that the mitogen-activated protein kinase (MAPK) pathway is operative during human NKT-cell autoreactive activation, but calcium signaling is severely impaired.

Modulation of CD1d-restricted NKT cell responses by CD4.

CD4+ and CD4- NKT cell populations have been shown to be functionally distinct, but the role of CD4 molecules in NKT cell activation is not clear. Here, we have used human CD1d-restricted NKT cell clones to investigate the contribution of CD4 to NKT cell functional responses. Coligation of CD4 with the TCR/CD3 complex resulted in enhanced cytokine secretion and increased calcium flux by CD4+ NKT cell clones, indicating that CD4 is functionally active in these cells.

Distinct endosomal trafficking requirements for presentation of autoantigens and exogenous lipids by human CD1d molecules.

CD1d molecules present both self Ags and microbial lipids to NKT cells. Previous studies have established that CD1d lysosomal trafficking is required for presentation of autoantigens to murine invariant NKT cells. We show in this study that this is not necessary for autoantigen presentation by human CD1d, but significantly affects the presentation of exogenous Ags.

NKT cells direct monocytes into a DC differentiation pathway.

Monocytes can differentiate into macrophages or dendritic cells (DCs). The processes that promote their differentiation along one pathway rather than the other remain unknown. NKT cells are regulatory T cells that respond functionally to self and foreign antigens presented by CD1d molecules.

Conserved and heterogeneous lipid antigen specificities of CD1d-restricted NKT cell receptors.

CD1d-restricted NKT cells use structurally conserved TCRs and recognize both self and foreign glycolipids, but the TCR features that determine these Ag specificities remain unclear. We investigated the TCR structures and lipid Ag recognition properties of five novel Valpha24-negative and 13 canonical Valpha24-positive/Vbeta11-positive human NKT cell clones generated using alpha-galactosylceramide (alpha-GalCer)-loaded CD1d tetramers. The Valpha24-negative clones expressed Vbeta11 paired with Valpha10, Valpha2, or Valpha3.

Intracellular protein phosphorylation in adherent U937 monocytes mediated by various culture conditions and fibronectin-derived surface ligands.

Macrophages play a central role in the normal healing process after tissue injury and the host response to foreign objects such as biomaterials. The process leading to macrophage adhesion and activation on protein-adsorbed substrates is complex and unresolved. While the use of primary cells offers clinical relevancy, macrophage cell lines offer unique advantages such as availability and relatively homogeneous phenotype as models to probe the molecular mechanism of cell-surface interaction.

Less cytotoxicity to combination therapy of 5-fluorouracil and cisplatin than 5-fluorouracil alone in human colon cancer cell lines.

Aim: Our previous studies showed increased sensitivity to 5-FU in colon cancer cell lines with microsatellite instability, and considered that mutations of TGFbeta-R II, IGF IIR, RIZ gene might enhance the potentials of cell growth and proliferation, which increased the sensitivity to 5-FU. Here we compared the distribution of cell cycle and P53 status between two human colon cancer cell lines with different sensitivity to 5-FU. Because mechanistic differences exist between 5-FU and CDDP, we also analyzed the efficacy of CDDP and combination therapy on two human colon cancer cell lines.