APOE and FABP2 Polymorphisms and History of Myocardial Infarction, Stroke, Diabetes, and Gallbladder Disease

Dysfunctional lipid metabolism plays a central role in pathogenesis of major chronic diseases, and genetic factors are important determinants of individual lipid profiles. We analyzed the associations of two well-established functional polymorphisms (FABP2 A54T and APOE isoforms) with past and family histories of 1492 population samples. FABP2-T54 allele was associated with an increased risk of past history of myocardial infarction (odds ratio (OR) = 1.51). Likewise, the subjects with APOE4, compared with E2 and E3, had a significantly increased risk of past history myocardial infarction (OR = 1.89). The OR associated with APOE4 was specifically increased in women for past history of myocardial infarction but decreased for gallstone disease. Interactions between gender and APOE isoforms were also significant or marginally significant for these two conditions. FABP2-T54 allele may be a potential genetic marker for myocardial infarction, and APOE4 may exert sex-dependent effects on myocardial infarction and gallbladder disease

Immunohistochemical Examination on the Distribution of Cells Expressed Lymphatic Endothelial Marker Podoplanin and LYVE-1 in the Mouse Tongue Tissue

The clinical study for lingual disease requires the detailed investigation of the lingual lymphatic network and lymphatic marker-positive cells. Recently, it has been reported that several tissue cells and leukocytes express lymphatic markers, LYVE-1 and podoplanin. This study was aimed to clarify the lingual distribution of cells expressing LYVE-1 and podoplanin. In the mouse tongue, podoplanin is expressed in nerve sheaths, lingual gland myoepithelial cells, and lymphatic vessels. LYVE-1 is expressed in the macrophage marker Mac-1-positive cells as well as lymphatic vessels, while factor-VIII was detected in only blood endothelial cells. α-SMA was detected in vascular smooth muscle and myoepithelial cells. Therefore, identification of lymphatic vessels in lingual glands, the combination of LYVE-1 and factor-VIII, or LYVE-1 and Mac-1 is useful because myoepithelial cells express podoplanin and α-SMA. The immunostaining of factor-VIII on lymphatic vessels was masked by the immunostaining to LYVE-1 or podoplanin because lymphatic vessels express factor-VIII to a far lesser extent than blood vessels. Therefore, except for the salivary glands, the combination of podoplanin and α-SMA, or factor-VIII is useful to identify lymphatic vessels and blood vessels with smooth muscle, or blood capillaries

Quantitative analysis of thrombopoietin receptors on human megakaryocytes

AbstractThrombopoietin (TPO), or c-MPL ligand, is the primary regulator of megakaryocyte and platelet production. TPO receptors expressed on human megakaryocytes derived from peripheral blood (PB) and cord blood (CB) progenitors cultured in the presence of TPO have now been analyzed quantitatively. Like those on human PB platelets, TPO receptors on the cultured megakaryocytes exhibited a molecular mass of approximately 80 kDa. Various characteristics of PB- and CB-derived megakaryocytes indicated that the former were more mature than the latter. Both PB- and CB-derived megakaryocytes expressed a single class of high-affinity TPO receptors, with 1933±772 (n=3) and 184±48 (n=4) sites per cell, respectively. These data indicate that the number of TPO receptors on human megakaryocytes increases with cell maturation

Activity-dependent oligodendrocyte calcium dynamics and their changes in Alzheimer’s disease

Oligodendrocytes (OCs) form myelin around axons, which is dependent on neuronal activity. This activity-dependent myelination plays a crucial role in training and learning. Previous studies have suggested that neuronal activity regulates proliferation and differentiation of oligodendrocyte precursor cells (OPCs) and myelination. In addition, deficient activity-dependent myelination results in impaired motor learning. However, the functional response of OC responsible for neuronal activity and their pathological changes is not fully elucidated. In this research, we aimed to understand the activity-dependent OC responses and their different properties by observing OCs using in vivo two-photon microscopy. We clarified that the Ca2+ activity in OCs is neuronal activity dependent and differentially regulated by neurotransmitters such as glutamate or adenosine triphosphate (ATP). Furthermore, in 5-month-old mice models of Alzheimer’s disease, a period before the appearance of behavioral abnormalities, the elevated Ca2+ responses in OCs are ATP dependent, suggesting that OCs receive ATP from damaged tissue. We anticipate that our research will help in determining the correct therapeutic strategy for neurodegenerative diseases beyond the synapse

Immunohistochemical Examination for the Distribution of Podoplanin-Expressing Cells in Developing Mouse Molar Tooth Germs

We recently reported the expression of podoplanin in the apical bud of adult mouse incisal tooth. This study was aimed to investigate the distribution of podoplanin-expressing cells in mouse tooth germs at several developing stages. At the bud stage podoplanin was expressed in oral mucous epithelia and in a tooth bud. At the cap stage podoplanin was expressed on inner and outer enamel epithelia but not in mesenchymal cells expressing the neural crest stem cell marker nestin. At the early bell stage nestin and podoplanin were expressed in cervical loop and odontoblasts. At the root formation stage both nestin and podoplanin were weakly expressed in odontoblasts generating radicular dentin. Podoplanin expression was also found in the Hertwig epithelial sheath. These results suggest that epithelial cells of developing tooth germ acquire the ability to express nestin, and that tooth germ epithelial cells maintain the ability to express podoplanin in oral mucous epithelia. The expression of podoplanin in odontoblasts was induced as tooth germ development advanced, but was suppressed with the completion of the primary dentin, suggesting that podoplanin may be involved in the cell growth of odontoblasts. Nestin may function as an intermediate filament that binds podoplanin in odontoblasts

Immunoelectron Microscopic Study of Podoplanin Localization in Mouse Salivary Gland Myoepithelium

We have recently reported that salivary gland cells express the lymphatic endothelial cell marker podoplanin. The present study was aimed to immunohistochemically investigate the expression of the myoepithelial cell marker α-smooth muscle actin (SMA) on podoplanin-positive cells in mouse parotid and sublingual glands, and to elucidate podoplanin localization in salivary gland myoepithelial cells by immunoelectron microscopic study. The distribution of myoepithelial cells expressing podoplanin and α-SMA was examined by immunofluorescent staining, and the localization of reaction products of anti-podoplanin antibody was investigated by pre-embedded immunoelectron microscopic method. In immunohistochemistry, the surfaces of both the mucous acini terminal portion and ducts were covered by a number of extensive myoepithelial cellular processes expressing podoplanin, and the immunostaining level with anti-podoplanin antibody to myoepithelial cells completely coincided with the immunostaining level with anti-α-SMA antibody. These findings suggest that podoplanin is a salivary gland myoepithelial cell antigen, and that the detection level directly reflects the myoepithelial cell distribution. In immunoelectron microscopic study, a number of reaction products with anti-podoplanin antibody were found at the Golgi apparatus binding to the endoplasmic reticulum in the cytoplasm of myoepithelial cells between sublingual gland acinar cells, and were also found at the myoepithelial cell membrane. These findings suggest that salivary gland myoepithelial cells constantly produce podoplanin and glycosylate at the Golgi apparatus, and transport them to the cell membrane. Podoplanin may be involved in maintaining the homeostasis of myoepithelial cells through its characteristic as a mucin-type transmembrane glycoprotein

Association of Cumulative Social Risk and Social Support With Receipt of Chemotherapy Among Patients With Advanced Colorectal Cancer

Importance: Approximately 38% of patients with advanced colorectal cancer do not receive chemotherapy. Objective: To determine whether cumulative social risk (ie, multiple co-occurring sociodemographic risk factors) is associated with lower receipt of chemotherapy among patients with advanced colorectal cancer and whether social support would moderate this association. Design, Setting, and Participants: This cross-sectional, population-based, mailed survey study was conducted from 2012 to 2014. Participants were recruited between 2011 and 2014 from all adults within 1 year after diagnosis of stage III colorectal cancer in the Detroit, Michigan, and State of Georgia Surveillance, Epidemiology, End-Results cancer registries. Patients were eligible if they were aged 18 years or older, had undergone surgery 4 or more months ago, did not have stage IV cancer, and resided in the registry catchment areas. Data analyses were conducted from March 2017 to April 2021. Main Outcomes and Measures: The primary outcome was receipt of chemotherapy. Cumulative social risk represented a sum of 8 risk factors with the potential to drain resources from participants\u27 cancer treatment (marital status, employment, annual income, health insurance, comorbidities, health literacy, adult caregiving, and perceived discrimination). Social support was operationalized as emotional support related to colorectal cancer diagnosis. Results: Surveys were mailed to 1909 eligible patients; 1301 completed the survey (response rate, 68%). A total of 1087 participants with complete data for key variables were included in the sample (503 women [46%]; mean [SD] age, 64 [13] years). Participants with 3 or more risk factors were less likely to receive chemotherapy than participants with 0 risk factors (3 factors, odds ratio [OR], 0.48 [95% CI, 0.26-0.87]; 4 factors, OR, 0.41 [95% CI, 0.21-0.78]; 5 factors, OR, 0.42 [95% CI, 0.20-0.87]; ≥6 factors, OR, 0.22 [95% CI, 0.09-0.55]). Participants with 2 or more support sources had higher odds of undergoing chemotherapy than those without social support (2 sources, OR, 3.05 [95% CI, 1.36-6.85]; 3 sources, OR, 3.24 [95% CI, 1.48-7.08]; 4 sources, OR, 3.69 [95% CI, 1.71-7.97]; 5 sources, OR, 4.40 [95% CI, 1.98-9.75]; ≥6 sources, OR 5.95 [95% CI, 2.58-13.74]). Within each social support level, participants were less likely to receive chemotherapy as cumulative social risk increased. Conclusions and Relevance: Cumulative social risk was associated with reduced receipt of chemotherapy. These associations were mitigated by social support. Assessing cumulative social risk may identify patients with colorectal cancer who are at higher risk for omitting chemotherapy who can be targeted for support programs to address social disadvantage and increase social support

The accuracy of chemotherapy ascertainment among colorectal cancer patients in the surveillance, epidemiology, and end results registry program

Abstract Background Surveillance, Epidemiology, and End Results (SEER) public research database does not include chemotherapy data due to concerns for incomplete ascertainment. To compensate for perceived lack of data quality many researchers use SEER-Medicare linked data, limiting studies to persons over age 65. We sought to determine current SEER ascertainment of chemotherapy receipt in two relatively large SEER registries compared to patient-reported receipt and to assess patterns of under-ascertainment. Methods In 2011–14, we surveyed patients with Stage III colorectal cancer reported to the Georgia and Metropolitan Detroit SEER registries. 1301/1909 eligible patients responded (68% response rate). Survey responses regarding treatment and sociodemographic factors were merged with SEER data. We compared patient-reported chemotherapy receipt with SEER recorded chemotherapy receipt. We estimated multivariable regression models to assess associations of under-ascertainment in SEER. Results Eighty-five percent of patients reported chemotherapy receipt. Among those, 10% (n = 104) were under-ascertained in SEER (coded as not receiving chemotherapy). In unadjusted analyses, under-ascertainment was more common for older patients (11.8% age 76+ vs. < 9% for all other ages, p = 0.01) and varied with SEER registries (10.2% Detroit vs. 6.8% Georgia; p = 0.04). On multivariable analyses, chemotherapy under-ascertainment did not vary significantly by any patient attributes. Conclusion We found a 10% rate of under-ascertainment of adjuvant chemotherapy for resected, stage III colorectal cancer in two SEER registries. Chemotherapy under-ascertainment did not disproportionately affect any patient subgroups. Use of SEER data from select registries is an important resource for researchers investigating contemporary chemotherapy receipt and outcomes.https://deepblue.lib.umich.edu/bitstream/2027.42/143192/1/12885_2018_Article_4405.pd