348 research outputs found

    Breastfeeding, breast milk and viruses

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    <p>Abstract</p> <p>Background</p> <p>There is seemingly consistent and compelling evidence that there is no association between breastfeeding and breast cancer. An assumption follows that milk borne viruses cannot be associated with human breast cancer.</p> <p>We challenge this evidence because past breastfeeding studies did not determine "exposure" of newborn infants to colostrum and breast milk.</p> <p>Methods</p> <p>We conducted a prospective review of 100 consecutive births of infants in the same centre to determine the proportion of newborn infants who were "exposed" to colostrum or breast milk, as distinct from being fully breast fed. We also report a review of the breastfeeding practices of mothers of over 87,000 newborn infants in the Australian State of New South Wales.</p> <p>This study was approved by the Human Research Ethics Committee of the University of New South Wales (Sydney, Australia). Approval 05063, 29 September 2005.</p> <p>Results</p> <p>Virtually all (97 of 100) newborn infants in this centre were "exposed" to colostrum or breast milk whether or not they were fully breast fed. Between 82.2% to 98.7% of 87,000 newborn infants were "exposed" to colostrum or breast milk.</p> <p>Conclusion</p> <p>In some Western communities there is near universal exposure of new born infants to colostrum and breast milk. Accordingly it is possible for the transmission of human milk borne viruses. This is contrary to the widespread assumption that human milk borne viruses cannot be associated with breast cancer.</p

    Expression of three forms of melanoma growth stimulating activity (MGSA)/gro in human retinal pigment epithelial cells

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    PURPOSE: To characterize mRNA expression and protein production of the cytokine MGSA/gro in human retinal pigment epithelial (RPE) cells and to determine whether expression of MGSA/gro is modulated by serum and the cytokines interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), or transforming growth factor beta (TGF beta) mediators implicated in proliferative vitreoretinopathy (PVR). METHODS: Reverse-transcription polymerase chain reaction was used to determine the steady-state mRNA expression of three forms of MGSA/gro, alpha, beta, and gamma, by cultured human RPE cells in the presence or absence of recombinant IL-1 beta, TNF alpha, or TGF beta, or when serum-starved cells were re-fed with medium containing serum. Immunocytochemistry was used to characterize RPE cell-associated MGSA/gro protein, and immunoprecipitation of MGSA/gro from cell-conditioned medium was used to demonstrate MGSA/gro secretion. RESULTS: MGSA/gro mRNA was expressed minimally under basal conditions. Expression for all three forms of MGSA/gro mRNA was induced in a dose- and time-dependent manner after exposure to IL-1 beta, to a lesser extent after exposure to TNF alpha, but not after exposure to TGF beta. Serum induced MGSA/gro alpha and gamma transcripts, but not beta transcripts. Cell-associated MGSA/gro was identified on RPE cells grown in the absence of cytokines, but MGSA/gro was not secreted under these conditions. Exposure to IL-1 beta did not consistently cause increased cell-associated MGSA/gro; however, IL-1 beta induced secretion of MGSA/gro in a time-dependent manner. CONCLUSION: MGSA/gro is produced by human RPE in response to mediators implicated in PVR. Because MGSA/gro is a pleiotropic modulator of cell proliferation and inflammation, it may contribute to the intraocular wound healing response that characterizes PVR

    Modification of 15q11 — q13 DNA methylation imprints in unique Angelman and Prader — Willi patients

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    The clearest example of genomic Imprinting in humans comes from studies of the Angelman (AS) and Prader—Wil (PWS) syndromes. Although these are clinically distinct disorders, both typically result from a loss of the same chromosomal region, 15q11 - q13. AS usually results from either a maternal deletion of this region, or paternal uniparental disomy (UPD; both chromosomes 15 Inherited from the father). PWS results from paternal deletion of 15q11 - q13 or maternal UPD of chromosome 15. We have recently described a parent-specific DNA methylation imprint in a gene at the D15S9 locus (new gene symbol, ZNF 127), within the 15q11 - q13 region, that identifies AS and PWS patients with either a deletion or UPD. Here we describe an AS sibship and three PWS patients in which chromosome 15 rearrangements alter the methylation state at ZNF127, even though this locus is not directly involved in the rearrangement. Parent-specific DNA methylation imprints are also altered at ZNF127 and D15S63 (another locus with a parent-specific methylation imprint) in an AS sibship which have no detectable deletion or UPD of chromosome 15. These unique patients may provide insight into the imprinting process that occurs in proximal chromosome 15 in human

    Three dimensional optic tissue culture and process

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    A process for artificially producing three-dimensional optic tissue has been developed. The optic cells are cultured in a bioreactor at low shear conditions. The tissue forms normal, functional tissue organization and extracellular matrix

    Lofar Low-Band Antenna Observations of the 3C 295 and Bootes Fields: Source Counts and Ultra-Steep Spectrum Sources

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    We present Low Frequency Array (LOFAR) Low Band observations of the Boötes and 3C 295 fields. Our images made at 34, 46, and 62 MHz reach noise levels of 12, 8, and 5 mJy beam-1, making them the deepest images ever obtained in this frequency range. In t

    Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery

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    BACKGROUND: Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified. RESULTS: To search for such proteins twenty three nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells. CONCLUSIONS: The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.Publisher PDFPeer reviewe

    ABCC Multidrug Transporters in Childhood Neuroblastoma: Clinical and Biological Effects Independent of Cytotoxic Drug Efflux

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    Background Although the prognostic value of the ATP-binding cassette, subfamily C (ABCC) transporters in childhood neuroblastoma is usually attributed to their role in cytotoxic drug efflux, certain observations have suggested that these multidrug transporters might contribute to the malignant phenotype independent of cytotoxic drug efflux. Methods A v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN)-driven transgenic mouse neuroblastoma model was crossed with an Abcc1-deficient mouse strain (658 hMYCN1/−, 205 hMYCN+/1 mice) or, alternatively, treated with the ABCC1 inhibitor, Reversan (n = 20). ABCC genes were suppressed using short interfering RNA or overexpressed by stable transfection in neuroblastoma cell lines BE(2)-C, SH-EP, and SH-SY5Y, which were then assessed for wound closure ability, clonogenic capacity, morphological differentiation, and cell growth. Real-time quantitative polymerase chain reaction was used to examine the clinical significance of ABCC family gene expression in a large prospectively accrued cohort of patients (n = 209) with primary neuroblastomas. Kaplan-Meier survival analysis and Cox regression were used to test for associations with event-free and overall survival. Except where noted, all statistical tests were two-sided. Results Inhibition of ABCC1 statistically significantly inhibited neuroblastoma development in hMYCN transgenic mice (mean age for palpable tumor: treated mice, 47.2 days; control mice, 41.9 days; hazard ratio [HR] = 9.3, 95% confidence interval [CI] = 2.65 to 32; P < .001). Suppression of ABCC1 in vitro inhibited wound closure (P < .001) and clonogenicity (P = .006); suppression of ABCC4 enhanced morphological differentiation (P < .001) and inhibited cell growth (P < .001). Analysis of 209 neuroblastoma patient tumors revealed that, in contrast with ABCC1 and ABCC4, low rather than high ABCC3 expression was associated with reduced event-free survival (HR of recurrence or death = 2.4, 95% CI = 1.4 to 4.2; P = .001), with 23 of 53 patients with low ABCC3 expression experiencing recurrence or death compared with 31 of 155 patients with high ABCC3. Moreover, overexpression of ABCC3 in vitro inhibited neuroblastoma cell migration (P < .001) and clonogenicity (P = .03). The combined expression of ABCC1, ABCC3, and ABCC4 was associated with patients having an adverse event, such that of the 12 patients with the "poor prognosis” expression pattern, 10 experienced recurrence or death (HR of recurrence or death = 12.3, 95% CI = 6 to 27; P < .001). Conclusion ABCC transporters can affect neuroblastoma biology independently of their role in chemotherapeutic drug efflux, enhancing their potential as targets for therapeutic interventio
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