Enhancer of the rudimentary gene homologue (ERH) expression pattern in sporadic human breast cancer and normal breast tissue

<p>Abstract</p> <p>Background</p> <p>The human gene <it>ERH </it>(Enhancer of the Rudimentary gene Homologue) has previously been identified by <it>in silico </it>analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1) via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of <it>ERH </it>expression in human breast cancer in order to evaluate possible clinical applications of this molecule.</p> <p>Methods</p> <p>The expression pattern of <it>ERH </it>was analyzed using multiple tissue northern blots (MTN) on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. <it>ERH </it>expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic <it>in situ </it>hybridization (ISH).</p> <p>Results</p> <p>Among normal human tissues, <it>ERH </it>expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,<it>ERH </it>was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that <it>ERH </it>expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test); the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1). These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue.</p> <p>Conclusion</p> <p><it>ERH </it>expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian cancer, ERH overexpression may be implicated in the initiation and/or progression of certain human malignancies. Further studies on large breast cancer tissue cohorts should determine whether ERH could function as a prognostic factor or even a drug target in the treatment of human breast cancer.</p

Promoter hypermethylation of the SFRP2 gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer

<p>Abstract</p> <p>Background</p> <p>We have previously reported that expression of the Wnt antagonist genes <it>SFRP1 </it>and <it>SFRP5 </it>is frequently silenced by promoter hypermethylation in breast cancer. SFRP2 is a further Wnt inhibitor whose expression was recently found being downregulated in various malignancies. Here we investigated whether SFRP2 is also implicated in human breast cancer, and if so whether <it>SFRP2 </it>promoter methylation might serve as a potential tumor biomarker.</p> <p>Methods</p> <p>We analyzed <it>SFRP2 </it>mRNA expression and <it>SFRP2 </it>promoter methylation in 10 breast cell lines, 199 primary breast carcinomas, 20 matched normal breast tissues and 17 cancer-unrelated normal breast tissues using RT-PCR, realtime PCR, methylation-specific PCR and Pyrosequencing, respectively. SFRP2 protein expression was assessed by immunohistochemistry on a tissue microarray. Proliferation assays after transfection with an <it>SFRP2 </it>expression vector were performed with mammary MCF10A cells. Statistical evaluations were accomplished with SPSS 14.0 software.</p> <p>Results</p> <p>Of the cancerous breast cell lines, 7/8 (88%) lacked <it>SFRP2 </it>mRNA expression due to <it>SFRP2 </it>promoter methylation (<it>P </it>< 0.001). <it>SFRP2 </it>expression was substantially restored in most breast cell lines after treatment with 5-aza-2'-deoxycytidine and trichostatin A. In primary breast carcinomas SFRP2 protein expression was strongly reduced in 93 of 125 specimens (74%). <it>SFRP2 </it>promoter methylation was detected in 165/199 primary carcinomas (83%) whereas all cancer-related and unrelated normal breast tissues were not affected by <it>SFRP2 </it>methylation. <it>SFRP2 </it>methylation was not associated with clinicopathological factors or clinical patient outcome. However, loss of SFRP2 protein expression showed a weak association with unfavorable patient overall survival (<it>P </it>= 0.071). Forced expression of <it>SFRP2 </it>in mammary MCF10A cells substantially inhibited proliferation rates (<it>P </it>= 0.045).</p> <p>Conclusion</p> <p>The <it>SFRP2 </it>gene is a high-frequent target of epigenetic inactivation in human breast cancer. Its methylation leads to abrogation of <it>SFRP2 </it>expression, conferring a growth advantage to epithelial mammary cells. This altogether supports a tumor suppressive function of <it>SFRP2</it>. Although clinical patient outcome was not associated with <it>SFRP2 </it>methylation, the high frequency of this epimutation and its putative specificity to neoplastic cells may qualify <it>SFRP2 </it>promoter methylation as a potential candidate screening marker helping to improve early breast cancer detection.</p

R ates and factors associated with falls in older European Americans, Afro-Caribbeans, African-Americans, and Hispanics

Purpose: To evaluate rates and factors associated with older adult falls in different ethnic groups. Participants and methods: Information on demographics, medical and falls history, and pain and physical activity levels was collected from 550 community-dwelling older adults (75±9 years old, 222 European Americans, 109 Afro-Caribbeans, 106 African-Americans, and 113 Hispanics). Results: Taking medications for anxiety (risk ratio [RR] =1.4, 95% confidence interval [CI] =1.1–2.0), having incontinence (RR =1.4, 95% CI =1.1–1.8, P=0.013), back pain (RR =1.4, 95% CI =1.0–1.8), feet swelling (RR =1.3, 95% CI =1.1–1.7), and age $75 years (RR =1.3, 95$75 years were associated with falls, and Afro-Caribbeans presented lower prevalence of falls. These findings need to be taken into consideration in clinical interventions in aging. Keywords: ethnicity, falls, risks, community dwelling, older adult

The axon-myelin unit in development and degenerative disease

Axons are electrically excitable, cable-like neuronal processes that relay information between neurons within the nervous system and between neurons and peripheral target tissues. In the central and peripheral nervous systems, most axons over a critical diameter are enwrapped by myelin, which reduces internodal membrane capacitance and facilitates rapid conduction of electrical impulses. The spirally wrapped myelin sheath, which is an evolutionary specialisation of vertebrates, is produced by oligodendrocytes and Schwann cells; in most mammals myelination occurs during postnatal development and after axons have established connection with their targets. Myelin covers the vast majority of the axonal surface, influencing the axon's physical shape, the localisation of molecules on its membrane and the composition of the extracellular fluid (in the periaxonal space) that immerses it. Moreover, myelinating cells play a fundamental role in axonal support, at least in part by providing metabolic substrates to the underlying axon to fuel its energy requirements. The unique architecture of the myelinated axon, which is crucial to its function as a conduit over long distances, renders it particularly susceptible to injury and confers specific survival and maintenance requirements. In this review we will describe the normal morphology, ultrastructure and function of myelinated axons, and discuss how these change following disease, injury or experimental perturbation, with a particular focus on the role the myelinating cell plays in shaping and supporting the axon

Sustaining or declining physical activity: Reports from an ethnically diverse sample of older adults

Over 80% of adults in the US fail to meet the ≥150 min weekly physical activity guideline; 40% age ≥ 75 are entirely inactive. The study purpose was to understand the reasons why community-dwelling older adults (age ≥ 60) from diverse backgrounds increase, sustain, or decline in their physical activity levels over time. Sixty-two older adults were interviewed. Two-thirds of the African Americans, 57% of the Afro-Caribbeans, and 50% of the European Americans reported being less active than 2–3 years ago. Reasons for activity decline included health issues (e.g., pain, shortness of breath), lack of time, interest, or motivation. Reasons for sustaining or increasing activity levels included meeting personal goals, having a purpose for remaining active, or feeling better when active (e.g., it is important to keep moving, good for the joints, going on a cruise). Themes identified were pride in maintaining activity, goal-driven activity, pushing oneself to get past pain or fatigue, and some confusion between social and physical activity in participant reports. The results indicate widespread acceptance that activity is beneficial, but that knowledge alone was insufficient to maintain activity levels over time unless individuals had a goal or purpose (“means to an end”) and could overcome their physical and psychological barriers to physical activity

Pruebas regionales para una variedad promisoria de pimentón evaluando varias dosis de n.

En la Universidad Nacional de Colombia en Palmira, Valle del Cauca, se realizó un experimento en dos suelos (isohipertérmico fino/franco fino Haplustol Vértico e isohipertérmico muy fino/ franco fino Epiaquert Ustico), tratados con seis dosis de úrea (O a 250 kg N ha-1) para crear 12 "ambientes" con el fin de evaluar la adaptabilidad de la línea promisoria 003 de pimentón, del Programa de Mejoramiento Genético y Producción de Semillas de esta Facultad, mediante la metodología de Eberhart y Russell (1966). En un clima favorable, la línea demostró adaptabilidad a todos los ambientes y sus rendimientos relativos y cantidad de frutos por planta fueron bastante altos: 417 g y 4.95 unidades respectivamente; su respuesta a los incrementos en la dosis de N. fue producir más cosecha  sin incrementar la altura y la dosis  250 Kg N ha-1 fue la mas económica. Para producir 400 g/planta se registró la siguiente extracción de nutrientes: 73 kg ha- N, 12 P, 57 K, 27 Ca, 12 Mg, 4 Na, 495 g ha-1Fe, 181 Mn, 36 Cu, 181 Zn y 5 B.At the National University of Colombia in Palmira, Valle del Cauca, was carried out an experiment to evaluate in 12 "environments" (two soils: an isohiperthermic fine/fine loam Vertic Haplustoll and an isohiperthermic very fine/fine loam Ustic Epiaquert, and six urea doses from 0 to 250 kg N ha-1) the adaptability of a 003 new pepper Capsicum annuum cultivar bred by a Genetic Program of this Faculty, using Eberhart and Russell's methodology (1966). Under a favorable weather the cultivar showed adaptability lo all environments and had a relatively high yield: 417 g/plant and 4.95 fruits/plant; the more soil N-doses the more its harvest with a stable height, and the best economic N-dose was 250 kg N ha-l. To produce 400 g/plant the 003 cultivar extracted 73 kg ha-1 N, 12 P, 57 K, 27 Ca, 12 Mg, 4 Na, 495g ha-1 Fe, 181 Mn, 36 Cu, 181 Zn and 5B

The Axon-Myelin Unit in Development and Degenerative Disease

Axons are electrically excitable, cable-like neuronal processes that relay information between neurons within the nervous system and between neurons and peripheral target tissues. In the central and peripheral nervous systems, most axons over a critical diameter are enwrapped by myelin, which reduces internodal membrane capacitance and facilitates rapid conduction of electrical impulses. The spirally wrapped myelin sheath, which is an evolutionary specialisation of vertebrates, is produced by oligodendrocytes and Schwann cells; in most mammals myelination occurs during postnatal development and after axons have established connection with their targets. Myelin covers the vast majority of the axonal surface, influencing the axon's physical shape, the localisation of molecules on its membrane and the composition of the extracellular fluid (in the periaxonal space) that immerses it. Moreover, myelinating cells play a fundamental role in axonal support, at least in part by providing metabolic substrates to the underlying axon to fuel its energy requirements. The unique architecture of the myelinated axon, which is crucial to its function as a conduit over long distances, renders it particularly susceptible to injury and confers specific survival and maintenance requirements. In this review we will describe the normal morphology, ultrastructure and function of myelinated axons, and discuss how these change following disease, injury or experimental perturbation, with a particular focus on the role the myelinating cell plays in shaping and supporting the axon

A prospective study of the sensitivity, specificity and diagnostic performance of soluble intercellular adhesion molecule 1, highly sensitive C-reactive protein, soluble E-selectin and serum amyloid A in the diagnosis of neonatal infection

<p>Abstract</p> <p>Background</p> <p>Diagnosis of neonatal infection is difficult, because of it's non-specific clinical presentation and the lack of reliable diagnostic tests. The purpose of this study was to examine the potential diagnostic value of serum soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), highly sensitive C-reactive protein (hsCRP) and serum amyloid A (SAA) measurements, both individually and in combination in the setting of a neonatal intensive care unit.</p> <p>Methods</p> <p>219 consecutive serum samples were taken from 149 infants undergoing sepsis work up in a neonatal intensive care unit. Clinical diagnosis was established in a prospective manner, blind to the results of the study measurements. Infants were classified by an experienced paediatrician as infected or not-infected, one week after presentation. Classification was based on clinical presentation, routine laboratory and radiological investigations and response to therapy. The infected group were sub-classified as (a) culture positive infection or (b) culture negative infection. sICAM-1, sE-selectin, hsCRP and SAA levels were determined from stored serum samples after diagnosis was established. Further sub-group analysis of results was undertaken according to early or late onset of infection and preterm or term status. Statistical analysis utilised Mann Whitney U test and ROC curve analysis.</p> <p>Results</p> <p>There were significantly increased serum levels of sICAM-1, hsCRP, E selectin (p < 0.001) and SAA (p = 0.004) in infected infants compared with non-infected. ROC curve analysis indicated area under the curve values of 0.79 (sICAM-1), 0.73 (hsCRP), 0.72 (sE-selectin) and 0.61 (SAA). ROC curve analysis also defined optimum diagnostic cut-off levels for each measurement. The performance characteristics of sICAM-1, hsCRP and sE-selectin included a high negative predictive value (NPV) for culture positive infection and this was enhanced by combination of all 4 measurements. Clinical subgroup analysis suggested particularly high NPV for early onset symptoms, however further studies are required to elucidate this finding.</p> <p>Conclusions</p> <p>All four study measurements demonstrated some diagnostic value for neonatal infection however sICAM-1, hsCRP and sE-selectin demonstrated the highest NPV individually. The optimum diagnostic cut off level for hsCRP measurement in this study was much lower than currently used in routine clinical practice. Use of a combination of measurements enhanced diagnostic performance, demonstrating sensitivity of 90.3% and NPV of 91.3%. This study suggests there may be value in use of several of these markers, individually and in combination to assist in excluding neonatal infection. Further work is needed to confirm a specific role in the exclusion of early onset infection.</p