Sheep metallothionein-III (MT-III) cDNA was isolated from a brain cDNA library and characterized. In contrast with MT-III from other species, sheep MT-III cDNA is predicted to encode a protein with ...significantly different metal-binding properties, owing to the loss of three of its cysteine residues. RT-PCR from other sheep confirmed that this aberrant structure is ubiquitous in this species. MT-III was successfully isolated from sheep brain, demonstrating that the cDNA does give rise to a protein product of the predicted structure. Sheep MT-III is similar to other mammalian MT-IIIs in that it retains the Cys-Pro-Cys-Pro motif which is thought to encode growth-inhibitory activity, and we show that it is likewise able to inhibit neuron survival in vitro. This is the first naturally occurring variant of MT-III (or any other major mammalian MT gene) which gives rise to a protein product. These findings are discussed in light of proposed roles of MT in the mammalian brain.
Skin needling is a technique used to improve the appearance of acne scarring.
To comprehensively review the medical literature regarding skin needling as a treatment for acne scarring.
A literature ...search was performed using the PubMed, Medline, and Embase databases, in addition to reviewing the bibliographies of relevant articles.
Ten studies presented patients treated with skin needling alone, while eight studies discussed skin needling in combination with other treatments for acne scarring. All studies showed improvements in scarring after needling, with 12 reporting statistical significance. The median number of treatments when needling was used alone was three, the median duration between treatments was 4 weeks, and the median needle length used was 1.5 mm. Reported adverse events were infrequent and included post-inflammatory hyperpigmentation, “tram track” scarring, acne, and milia. There were no reports of bacterial infections.
The studies reviewed were heterogeneous in design and of variable validity, with some not reporting statistical significance.
There is moderate evidence to suggest that skin needling is beneficial and safe for the treatment of acne scarring. However, double-blinded, randomized controlled trials are required to make more definitive conclusions.
Metastasis and resistance to chemotherapy are common features of progressed cancers. With respect to the latter phenotype, it is thought that during tumor growth drug-resistant cells arise ...spontaneously at rates characteristic of the genetic alterations involved. On application of chemotherapy, such variant tumor cells are more likely to survive, and they may eventually dominate, resulting in a non-responsive malignancy. Aspects of this model have been confirmed in a number of experimental systems and in patients. In contrast to our understanding of drug resistance, steps involved in the progression to metastatic spread of tumor cells are much less well-understood. In this review we describe methodologies of quantitative genetic analysis with reference to development of drug resistance. We then describe attempts by ourselves and others to use a similar approach to investigate metastatic properties. Based on these studies, we have proposed the quantitative 'dynamic heterogeneity' model of tumor metastasis, which is presented here. Using an 'experimental' metastasis assay and Luria-Delbruck fluctuation analysis, we determined that in murine KHT fibrosarcoma and B16 melanoma lines, 'metastatic' variants with a distinct phenotype are generated at high rates. These variants are relatively unstable resulting in a dynamic equilibrium between generation and loss of metastatic variants. The metastatic ability of such a tumor population is thus dependent on the frequency of a subpopulation of metastatic variants which are turning over rapidly. This dynamic heterogeneity model is able to quantitatively provide a unifying explanation for a wide range of observations concerning tumor heterogeneity and clonal instability. Genetic mechanisms involving rapid rates have been characterized in drug-resistant variants. We speculate that similar processes may be involved in different aspects of tumor progression such as those resulting in metastasis.
The INT Galactic Plane Survey (IGAPS) is the merger of the optical photometric surveys, IPHAS and UVEX, based on data from the Isaac Newton Telescope (INT) obtained between 2003 and 2018. Here, we ...present the IGAPS point source catalogue. It contains 295.4 million rows providing photometry in the filters, i, r, narrow-band Halpha, g and U_RGO. The IGAPS footprint fills the Galactic coordinate range, |b| < 5deg and 30deg < l < 215deg. A uniform calibration, referred to the Pan-STARRS system, is applied to g, r and i, while the Halpha calibration is linked to r and then is reconciled via field overlaps. The astrometry in all 5 bands has been recalculated on the Gaia DR2 frame. Down to i ~ 20 mag (Vega system), most stars are also detected in g, r and Halpha. As exposures in the r band were obtained within the IPHAS and UVEX surveys a few years apart, typically, the catalogue includes two distinct r measures, r_I and r_U. The r 10sigma limiting magnitude is ~21, with median seeing 1.1 arcsec. Between ~13th and ~19th magnitudes in all bands, the photometry is internally reproducible to within 0.02 magnitudes. Stars brighter than r=19.5 have been tested for narrow-band Halpha excess signalling line emission, and for variation exceeding |r_I-r_U| = 0.2 mag. We find and flag 8292 candidate emission line stars and over 53000 variables (both at >5sigma confidence). The 174-column catalogue will be available via CDS Strasbourg.
ABSTRACT
Objective: The objective of this study was to explore the degree of parenchymal cell injury after mast cell degranulation by application of compound 48/80 (CMP 48/80) in the absence of ...adherent leukocytes in the rat mesentery.
Methods: Rats were rendered leukopenic by injection of an antibody against leukocytes, and the mesentery was superfused with CMP 48/80 during intravital microscopy. The extent of cell injury was determined using a fluorescent cellviability indicator, propidium iodide (PI). In an additional group, mast cell degranulation with CMP 48/80 was prevented by using the mast cell stabilizer Ketotifen.
Results: After a reduction in the number of circulating leukocytes, mast cell degranulation produced a mild increase in parenchymal cell injury. The injury levels significantly increased when individual regions of the mesentery were compared. Stabilization of the mast cells with Ketotifen reduced the injury to below baseline values.
Conclusions: In the absence of leukocyte adhesion to the endothelium, mast cell degranulation contributes to parenchymal cell injury in the mesentery.
BACKGROUND: Guidelines exist for treatment of low bone mineral density (BMD). Little is known about patient characteristics associated with use of treatment.
OBJECTIVES: To determine patient‐related ...correlates of medication use following screening dual x‐ray absorptiometry (DXA) of older adults.
DESIGN: Secondary analysis of a prospective cohort study.
SETTING: Pittsburgh, PA and Memphis, TN.
PARTICIPANTS: Community‐dwelling women between the ages 70 and 79 years enrolled in the Health, Aging, and Body Composition (Health ABC) Study.
MEASUREMENTS: Risk factors for fracture and BMD of the hip were assessed at baseline. Patients and their community physicians were supplied the results of the DXA scan. Prescription and over‐the‐counter medication use was collected at annual exams for 2 years.
RESULTS: Of 1,584 women enrolled in Health ABC, 378 had an indication for antifracture therapy and were not receiving such treatment at baseline. By the second annual follow‐up examination, prescription antiresorptive medication was reported in 49 (13.0%), whereas 65 (17.2%) received calcium and/or vitamin D supplementation. In adjusted models, the strongest predictor for use of any antifracture medicine was presence of osteoporosis vs osteopenia, odds ratio (OR), 2.9 (1.7 to 4.7), white race OR, 2.6 (1.5 to 4.8), and receipt of the flu shot OR, 2.2 (1.3 to 3.8). Neither a history of falls nor prior fracture was associated with use of antifracture medications.
CONCLUSION: Even when physicians of study participants were provided with DXA scan results, 70% of older high‐functioning women with an indication for therapy did not start or remain on an antifracture therapy. Substantial room for improvement exists in fracture prevention following a diagnosis of low BMD—especially among women with a history of falls, prior fractures, and among black women.
The relationship between infant pediatric care use in the first year of life and the quality of mother-infant attachment at 1-year of age was examined. Fifty-six mother and infant pairs were ...classified by the Ainsworth Strange Situation procedure as securely (n = 17) or anxiously attached (n = 39). Pediatric records for the first 12 months of life were reviewed for frequency and type of visit, diagnoses, treatment, and symptoms prompting the care visit. Anxiously attached infants used acute care services (walk-in and emergency room) significantly earlier and more often than infants with a secure attachment. Use of acute care services began at a mean age of 3.8 months for the anxiously attached infants compared with 6.5 months for the securely attached. Differences in utilization persisted through the year. Mean acute care use in the anxiously attached infants was 3.6 visits compared with 1.9 visits for the securely attached. Acute care use was associated with a variety of common infant illnesses in both groups. In contrast, there was no difference in the use of well-baby care (mean 6 visits). Utilization and attachment status were independent of birth or prenatal difficulties. High cumulative use of pediatric care during the first year of life may identify infant and mother pairs who are experiencing strain in their interactions and relationship. Early recognition would provide an opportunity for comprehensive assessment and preventive intervention in the pediatric setting.
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