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Objectives We sought to characterize the immunophenotype of acute myeloid leukemia (AML) with CBFB rearrangement and correlate the results with cytogenetic and molecular data. Methods Sixty-one cases of AML with CBFB rearrangement were evaluated. Results The sample population consisted of 33 men and 28 women, with a median age of 49 years. Flow cytometry immunophenotypic analysis showed that myeloblasts were positive for CD34 and CD117 in all cases, and myeloperoxidase was positive in 52 of 55 (95%) cases. The most common abnormalities included decreased CD38 in 90%, increased CD13 in 85%, increased CD123 in 84%, and decreased HLA-DR in 84% of cases. Monocytes were increased, with a mature immunophenotype, and accounted for 23.7% of total cells. Among 60 cases with available karyotype, inv(16)(p13.1q22) was most common in 50 (83%) cases, followed by t(16;16) (p13.1;q22) in 6 (10%). Type A CBFB::MYH11 transcript was most common, detected in 84% of cases. Mutational analysis showed mutations of NRAS in 37%, FLT3 in 25%, and KIT in 24% of cases. Comparing cases with type A vs non–type A transcripts, blasts in type A cases more frequently exhibited CD64 positivity and increased CD13 levels while showing a lower frequency of CD7 and CD56 expression. Trisomy 22 and mutations in KIT, NF1, and TET2 were identified only in cases with type A transcript. Conclusions Myeloblasts of AML with CBFB rearrangement are positive for CD34, CD117, and myeloperoxidase. These neoplasms most frequently carry inv(16)(p13.1q22) and type A fusion transcript. NRAS mutation was the most common mutation. Some immunophenotypic and genetic correlations occurred with different types of transcripts. [ABSTRACT FROM AUTHOR]

Objective(s): To validate certain markers for cancer stem cell populations and their clinical importance in Wilms tumor (WT) Materials and Methods: Immunohistochemical study for CD133 and CD56/NCAM was performed on forty-six cases of WT that were diagnosed between 1999 and 2015, and the association of these markers with survival and prognostic factors was analyzed. Results: Thirty-four (73.9%) of WTs were positive for CD133 and thirty-nine (84.8%) were positive for CD56/NCAM. A significant positive correlation between CD133 and CD56/NCAM expression and the National Wilms Tumor Stage (NWTS) and death was found. Moreover, overall survival time was significantly correlated with CD133 and CD56/NCAM H-score, NWTS stage, and death. Conclusion: It seems that CD133 and CD56/NCAM expressions can be used as strong prognostic parameters for the survival of patients with WT and can be used to predict WT patients' stage. Moreover, their targeted therapies can abolish cancer stem cells in children with recurrent tumors. [ABSTRACT FROM AUTHOR]

Objectives: INSM1 has been described as a sensitive and specific neuroendocrine marker. This study aims to compare INSM1 with traditional neuroendocrine markers in gastrointestinal neuroendocrine neoplasms.Methods: Retrospective review (2008-2018) was used to retrieve paraffin-embedded tissue from 110 gastrointestinal neuroendocrine neoplasms and controls that was subsequently stained with INSM1, synaptophysin, chromogranin, CD56, and Ki-67.Results: INSM1 was positive in 16 of 17 (94.1%) gastric, 17 of 18 (94.4%) pancreatic, 13 of 18 (72.2%) small bowel, 17 of 21 (81.0%) colonic, and 26 of 36 (72.2%) appendiceal tumors. INSM1 was positive in 58 of 70 (82.9%) well-differentiated neuroendocrine tumors, 17 of 20 (85.0%) poorly differentiated neuroendocrine carcinomas, 8 of 11 (72.7%) low-grade goblet cell adenocarcinomas (grade 1), and 6 of 9 (66.7%) high-grade goblet cell adenocarcinomas (grade 2/3). INSM1 sensitivity for neuroendocrine neoplasms (80.9%) was less than that of synaptophysin (99.1%), chromogranin (88%), and CD56 (95.3%); specificity was higher (95.7% vs 86.0%, 87.3%, and 86.0%, respectively).Conclusions: INSM1 is a useful marker of neuroendocrine differentiation in gastrointestinal neuroendocrine and mixed neuroendocrine neoplasms. Compared with traditional neuroendocrine markers, INSM1 is less sensitive but more specific. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the ability of routine flow cytometry (FC) to detect nonhematologic neoplasms (non-HN) using antibody panels routinely used for the diagnosis of hematologic neoplasms.Methods: FC analyses of 4,000 various diagnostic samples were retrospectively reviewed to identify cases in which an aberrant, viable CD45-negative, nonhematologic neoplastic population was detected by FC panels designed to evaluate hematologic neoplasms.Results: A total of 57 (1.4%) diverse non-HNs were identified, representing neuroendocrine tumors (33/57) and carcinomas (9/57), as well as other malignancies (15/57) such as sarcoma and melanoma. The majority of neoplasms were positive for at least one antibody, typically CD56 (43/51, 84.3%), followed by CD117 (15/34, 44.1%) and CD138 (6/33, 18.2%).Conclusions: Our findings highlight the importance of carefully inspecting CD45-negative events to identify non-HNs by routine FC analysis. This can help expedite further downstream immunophenotypic analysis of specimens and triage samples for appropriate genetic and molecular studies. [ABSTRACT FROM AUTHOR]

Objective : Repair of sensorial nerve defect is an important issue on peripheric nerve surgery. The aim of the present study was to determine the effects of sensory-motor nerve bridging on the denervated dermatomal area, in rats with sensory nerve defects, using a neural cell adhesion molecule (NCAM). Methods : We compared the efficacy of end-to-side (ETS) coaptation of the tibial nerve for sural nerve defect repair, in 32 Sprague- Dawley rats. Rats were assigned to 1 of 4 groups : group A was the sham operated group, group B rats had sural nerves sectioned and buried in neighboring muscles, group C experienced nerve sectioning and end-to-end (ETE) anastomosis, and group D had sural nerves sectioned and ETS anastomosis was performed using atibial nerve bridge. Neurological evaluation included the skin pinch test and histological evaluation was performed by assessing NCAM expression in nerve terminals. Results : Rats in the denervated group yielded negative results for the skin pinch tests, while animals in the surgical intervention groups (group C and D) demonstrated positive results. As predicted, there were no positively stained skin specimens in the denervated group (group B); however, the surgery groups demonstrated significant staining. NCAM expression was also significantly higher in the surgery groups. However, the mean NCAM values were not significantly different between group C and group D. Conclusion : Previous research indicates that ETE nerve repair is the gold standard for peripheral nerve defect repair. However, ETS repair is an effective alternative method in cases of sensorial nerve defect when ETE repair is not possible. [ABSTRACT FROM AUTHOR]

Immunoglobulin superfamily adhesion molecules are among the most abundant proteins in vertebrate and invertebrate nervous systems. Prominent family members are the neural cell adhesion molecules NCAM and L1, which were the first to be shown to be essential not only in development but also in synaptic function and as key regulators of synapse formation, synaptic activity, plasticity, and synaptic vesicle recycling at distinct developmental and activity stages. In addition to interacting with each other, adhesion molecules interact with ion channels and cytokine and neurotransmitter receptors. Mutations in their genes are linked to neurological disorders associated with abnormal development and synaptic functioning. This review presents an overview of recent studies on these molecules and their crucial impact on neurological disorders. [ABSTRACT FROM AUTHOR]

The neural IgCAM family of cell adhesion molecules, which includes NCAM and related molecules, has evolved via gene duplication and alternative splicing to allow for a wide range of isoforms with distinct functions and homophilic binding properties. A search for neural IgCAMs in ascidians ( Ciona intestinalis , Ciona savignyi , and Phallusia mammillata ) has identified a novel set of truncated family members that, unlike the known members, lack fibronectin III domains and consist of only repeated Ig domains. Within the tunicates this form appears to be unique to the ascidians, and it was designated ACAM, for Ascidian Cell Adhesion Molecule. In C. intestinalis ACAM is expressed in the developing neural plate and neural tube, with strongest expression in the anterior sensory vesicle precursor. Unlike the two other conventional neural IgCAMs in C. intestinalis , which are expressed maternally and throughout the morula and blastula stages, ACAM expression initiates at the gastrula stage. Moreover, C. intestinalis ACAM is a target of the homeodomain transcription factor OTX, which plays an essential role in the development of the anterior central nervous system. Morpholino (MO) knockdown shows that ACAM is required for neural tube closure. In MO-injected embryos neural tube closure was normal caudally, but the anterior neuropore remained open. A similar phenotype was seen with overexpression of a secreted version of ACAM. The presence of ACAM in ascidians highlights the diversity of this gene family in morphogenesis and neurodevelopment. [ABSTRACT FROM AUTHOR]

The neurotoxic effects of thinner, a mixture including aromatic compounds (in particular, toluene) and widely used as an industrial solvent, were examined. Exposure of rats to high inhalation concentrations (3000 p.p.m.) of thinner for 45 days (1 h per day) significantly influenced the cognitive functions and levels of neural cell adhesion molecules (NCAM) in the hippocampus, cortex, and cerebellum of experimental animals. These exposures also caused dramatic increases in levels of LPO (malondialdehyde and 4-hydroxyalkenals) in these cerebral structures, while melatonin administration significantly reduced the LPO amounts in these brain regions. The level of NCAM (180 kDa) decreased significantly in the hippocampus and cortex of thinner-exposed rats. Furthermore, thinner-exposed rats showed cognitive deficits in the passive avoidance and Morris water maze tasks; these negative effects were considerably compensated in rats additionally chronically treated with melatonin. It is concluded that treatment with melatonin prevents the development of learning and memory deficits caused by thinner exposure, possibly by reducing oxidative stress and normalizing the neural plasticity. [ABSTRACT FROM AUTHOR]

Abstract: The mechanisms underlying the neurotoxicity of endemic fluorosis still remain unknown. To investigate the expression level of neural cell adhesion molecules (NCAM), oxidative stress, and apoptosis induced by fluoride, the primary rat hippocampal neurons were incubated with 20, 40, and 80mg/l sodium fluoride for 24h in vitro. The results showed that the cell survival rate in the 80mg/l fluoride-treated group was significantly lower than that of the control group. Forty and 80mg/l of fluoride induced significantly increased lactate dehydrogenase release, intracellular reactive oxygen species, and the percentage of apoptosis. Compared with control group, the malondialdehyde levels were significantly elevated while glutathione levels and glutathione peroxidase activities were decreased in all fluoride-treated groups, accompanied by the markedly reduced superoxide dismutase activity in 80mg/l fluoride-treated group. With respect to NCAM mRNA expression levels, a significant dose-dependent decrease was observed in 40 and 80mg/l fluoride-treated groups against the control group. In addition, as compared to the control group, the protein expression levels of NCAM-180 in 40 and 80mg/l fluoride-treated groups, NCAM-140 in all fluoride-treated groups, and NCAM-120 in the 80mg/l fluoride-treated group were significantly decreased. Our study herein suggested that fluoride could cause oxidative stress, apoptosis, and decreased mRNA and protein expression levels of NCAM in rat hippocampal neurons, contributing to the neurotoxicity induced by fluoride. [Copyright &y& Elsevier]

Critical interactions between genetic and environmental factors – among which stress is one of the most potent non-genomic factors – are involved in the development of mood disorders. Intensive work during the past decade has led to the proposal of the network hypothesis of depression [Castren E: Nat Rev Neurosci 2005;6:241–246]. In contrast to the earlier chemical hypothesis of depression that emphasized neurochemical imbalance as the cause of depression, the network hypothesis proposes that problems in information processing within relevant neural networks might underlie mood disorders. Clinical and preclinical evidence supporting this hypothesis are mainly based on observations from depressed patients and animal stress models indicating atrophy (with basic research pointing at structural remodeling and decreased neurogenesis as underlying mechanisms) and malfunctioning of the hippocampus and prefrontal cortex, as well as the ability of antidepressant treatments to have the opposite effects. A great research effort is devoted to identify the molecular mechanisms that are responsible for the network effects of depression and antidepressant actions, with a great deal of evidence pointing at a key role of neurotrophins (notably the brain-derived neurotrophic factor) and other growth factors. In this review, we present evidence that implicates alterations in the levels of the neural cell adhesion molecules of the immunoglobulin superfamily, NCAM and L1, among the mechanisms contributing to stress-related mood disorders and, potentially, in antidepressant action. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Chronic alcohol exposure causes functional and structural changes in nervous system which have all been associated with learning and memory impairments. Furthermore, alcohol consumption has been shown to alter the pattern of neural cell adhesion molecules (NCAM) which are involved in memory processes. In the current work, we investigated the effects of melatonin on learning and memory deficits induced by alcohol exposure in young and aged rats. A group of young rats (3 months old) were administered ethanol for 45 days and half of them were co-treated with melatonin. Similar treatments were performed in the aged (19 months old) rats. Morris water maze test and passive avoidance task were used to assess cognitive performance. Lipid peroxidation (LPO) and glutathione (GSH) levels were determined to characterize the level of oxidative stress in the hippocampus and cortex. NCAM levels were determined by Western blotting in the hippocampal homogenates. There was a significant elevation in LPO levels and a reduction in GSH levels in aged and alcohol-exposed rats. Furthermore, both young and aged rats displayed some cognitive impairment when given with alcohol for 45 days. Co-administration of melatonin with ethanol significantly reduced LPO and elevated GSH levels while improving the learning and memory deficits induced by ethanol; the aged rats exhibited a greater response to melatonin supplementation. Moreover, melatonin modulated NCAM expression in hippocampus. Present findings indicate that exposure to ethanol induces learning and memory deficits probably by generating reactive oxygen species and downregulating NCAM 180 in hippocampus of aged rats. Melatonin improves learning and memory deficits and the behavioral responses of rats to melatonin supplementation are age dependent. [ABSTRACT FROM AUTHOR]

Thinner is a neurotoxic mixture which is widely used as an aromatic industrial solvent. This product has been shown to cause functional and structural changes in the central nervous system. We investigated the effect of exposure to high concentrations (3000 p.p.m.) of thinner for 45 days (1 hr/day) on cognitive functions and the levels of neural cell adhesion molecules (NCAM) and lipid peroxidation products (LPO) in the hippocampus, cortex and cerebellum of rats. The actions of melatonin on the effects produced by thinner exposure were also tested. Thinner exposure caused a significant increase in LPO (malondialdehyde and 4-hydroxyalkenals) in all brain regions. Melatonin administration significantly reduced LPO and elevated glutathione levels in the brain regions. NCAM (180 kDa) was significantly decreased in hippocampus and cortex of thinner-exposed rats. Furthermore, thinner-exposed rats showed cognitive deficits in passive avoidance and Morris water maze tasks, whereas in the rats chronically treated with melatonin these effects were reversed. This study indicates that treatment with melatonin prevents learning and memory deficits caused by thinner exposure possibly by reducing oxidative stress and regulating neural plasticity. [ABSTRACT FROM AUTHOR]

Although chronic stress has been reported to induce deleterious effects on hippocampal structure and function, the possible existence of individual differences in the vulnerability to develop stress-induced cognitive alterations was hypothetized. This study was designed to evaluate (i) whether individual variability in behavioural reactivity to novelty could be related to a differential vulnerability to show spatial learning deficits after chronic stress in young adult rats, and (ii) to what extent, could individual differences in stress-induced cognitive alterations be related to alterations in specific neurobiological substrates. Four month-old Wistar male rats were classified according to their locomotor reactivity to a novel environment, as either low (LR) or highly (HR) reactive, and then either submitted to psychosocial stress for 21-days (consisting of the daily cohabitation of each young adult rat with a new middle-aged rat) or left undisturbed. The results showed that psychosocial stress induced a marked deficit in spatial learning in the water maze in HR, but not in LR, rats. Then, a second experiment investigated the possible differential expression of corticosteroid receptors (MR and GR) and cell adhesion molecules (NCAM and L1) in the hippocampus of HR and LR rats, both under basal conditions and after exposure to chronic social stress. Although chronic stress induced a reduction on the hippocampal expression of MRs and the NCAM-140 isoform, the levels of these molecules did not differ between stressed rats with and without spatial learning impairments; i.e., between HR- and LR-stressed rats, respectively. Nevertheless, it should be noted that the reduction of the hippocampal expression of NCAM-140 induced by psychosocial stress was particularly marked in HR stressed rats. However, the expression of GRs, NCAM-120 and NCAM-180 isoforms, and L1, was not affected by stress, regardless of the reactivity of the animals. Therefore, although we failed to find a neurobiological substrate that specifically correlated with the differential cognitive vulnerability to chronic stress shown by animals with a different novelty reactivity, this study confirms the hypothesis that rats differ in their susceptibility to display stress-induced impairments in hippocampus-dependent spatial learning tasks. In addition, it provides a model to further search for the neurobiological substrate(s) involved in the differential susceptibility to develop stress-induced cognitive impairments. [Copyright &y& Elsevier]

Estrogens exhibit complex but beneficial effects on brain structure, function and behavior. Soy-derived dietary phytoestrogens protect against hormone-dependent and age-related diseases, due to their estrogen-like hormonal actions. However, the effects of phytoestrogens on brain and behavior are relatively unknown. This study examined the influence of exposing male Long–Evans rats (lifelong) to either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free) diet on body weights, behavioral pain thresholds, the hypothalamic–pituitary–adrenal (HPA) hormonal stress response, hippocampal glucocorticoid receptor and brain neural cell adhesion molecules (NCAM) and synaptophysin levels using standard behavioral and biochemical techniques. Body weights were significantly decreased in Phyto-600 fed animals compared to Phyto-free values. There were no significant changes in behavioral pain thresholds, circulating corticosterone concentrations (after acute immobilization stress) or NCAM and synaptophysin levels in various brain regions by the diet treatments. However, Phyto-600 fed males displayed significantly higher plasma adrenocorticotrophin (ACTH) (post-stress) and hippocampal glucocorticoid receptor levels vs. Phyto-free values. These data suggest that (1) body weights are significantly reduced by soy-derived phytoestrogens, (2) behavioral pain thresholds (via heat stimuli) are not influenced by dietary phytoestrogens, but (3) these estrogenic molecules in the hippocampus enhance glucocorticoid receptor abundance and alter the negative feedback of stress hormones towards a female-like pattern of higher ACTH release after activation of the HPA stress axis. This study is the first to show that lifelong consumption of dietary phytoestrogens alters the HPA stress response in male rats. [Copyright &y& Elsevier]

Background. Hypoganglionosis (HP) is characterized histologically by a decreased number of ganglion cells in intestinal myenteric plexuses and functionally by severely impaired gut motility. The purpose of the present study was to investigate the neuromuscular junction (NMJ) in small- and large-intestine biopsy specimens from patients with HP. Methods. Fresh frozen sections of small and large intestine from three patients with HP and five age/site-matched controls were examined. All specimens were labeled with neural cell adhesion molecule (NCAM) antibodies and synaptophysin (SY) antibodies to delineate the NMJ. Results. Normal small- and large-intestine specimens had a moderate number of NCAM-positive NMJ in association with nerve fibers in the lamina propria, muscularis mucosa, and many NCAM-positive NMJ in association with nerve fibers in the circular and longitudinal muscle layers. In HP, there was lack of expression of NCAM-positive NMJ in association with nerve fibers in the lamina propria, muscularis mucosa, and circular and longitudinal muscle layers in both small- and large-intestine specimens, and a marked increase in NCAM expression in the muscularis mucosa and the inner border of the circular muscle layer that was only seen in HP specimens. SY-positive synaptic vesicles were observed throughout the gut in all normal specimens, but there was a lack of SY expression in HP specimens. Expression of NCAM and SY in ganglion cells was the same in all specimens. Conclusion. These findings suggest there is a complicated abnormality of the NMJ in HP that may prove to contribute to the disturbances in gut motility seen in this condition. [ABSTRACT FROM AUTHOR]

Abstract: Neural cell adhesion molecules (NCAMs) play critical roles during development of the nervous system. The aim of this study is to investigate the possible effect of ethanol exposure on the pattern of expression and sialylation of NCAM isoforms during postnatal rat brain development because alterations in NCAM content and distribution have been associated with defects in cell migration, synapse formation, and memory consolidation, and deficits in these processes have been observed after in utero alcohol exposure. The expression of NCAM isoforms in the developing cerebral cortex of pups from control and alcohol-fed mothers was assessed by western blotting, ribonuclease protection assay, and immunocytochemistry. The highly sialylated form of NCAM [polysialic acid (PSA)-NCAM] is mainly expressed during the neonatal period and then is down-regulated in parallel with the appearance of NCAM 180 and NCAM 140. Ethanol exposure increases PSA-NCAM levels during the neonatal period, delays the loss of PSA-NCAM, decreases the amount of NCAM 180 and NCAM 140 isoforms, and reduces sialyltransferase activity during postnatal brain development. Neuraminidase treatment of ethanol-exposed neonatal brains leads to more intense band degradation products, suggesting a higher content of NCAM polypeptides carrying PSA in these samples. However, NCAM mRNA levels are not changed by ethanol. Immunocytochemical analysis demonstrates that ethanol triggers an increase in PSA-NCAM immunolabeling in the cytoplasm of astroglial cells, accompanied by a decrease in immunogold particles over the plasma membrane. These findings indicate that ethanol exposure during brain development alters the pattern of NCAM expression and suggest that modification of NCAM could affect neuronal-glial interactions that might contribute to the brain defects observed after in utero alcohol exposure. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy of neuroendocrine origin presenting as a painless, rapidly growing nodule. MCC often presents in elderly, fair-skinned individuals in sun-exposed areas. Diagnosis is often overlooked at time of presentation due to its rarity, but MCC is twice as deadly as malignant melanoma. There has been bigger interest in the disease due to increasing incidence and an association with the prevalent virus Merkel cell polyomavirus. This study describes an uncommon presentation of MCC as a right gluteal lesion in an Afro-Panamanian patient. The tumor was suspected to be fibrolipoma, but Immunohistochemistry revealed the diagnosis of MCC, as stains for CD56 and CK20 were positive. In addition to surgical excision, the patient was referred for adjuvant radiotherapy. This case report and literature review elucidates the clinical, histopathologic and management aspects of MCC, which will help in recognizing and treating these tumors. [ABSTRACT FROM AUTHOR]