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41.
Hansen LA; Malarkey DE; Wilkinson JE; Rosenberg M; Woychik RE; Tennant RW 《Carcinogenesis》1998,19(10):1837-1845
We previously reported that papillomas can arise from the follicular
epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow
mutation (A(vy)) of the mouse agouti gene which regulates coat color
pigmentation by acting within the micro-environment of the hair follicle
has been shown to function as a tumor promoter in the liver, we
hypothesized that it may also play a role in TGxAC skin tumorigenesis.
Endogenous agouti protein product was detected in the outer root sheath of
anagen hair follicles following plucking of the hair shaft, but not in the
interfollicular epithelium, in TGxAC mice on an FVB/N genetic background.
It was also detected in papillomas from these mice produced by
12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking.
Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line
results in an approximately 2-fold increase in papilloma development
compared with controls which did not carry the A(vy) allele following
twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition,
TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but
not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of
humoral hypercalcemia mediated by parathyroid hormone-related protein
(PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus,
we conclude that the A(vy) allele can influence the development of skin
tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic
TGxAC mice.
相似文献
42.
David Sumner BSc Dphil 《Medicine, conflict, and survival》2013,29(2):112-119
The main delayed effect of ionizing radiation in the individual is the induction of cancer. However, for low doses (less than 100 mSv effective dose equivalent), there is no direct evidence of radiation‐induced cancer, with the possible exception of childhood cancer following prenatal exposure to X‐rays. The risk at low doses has to be estimated from the observed risk at high doses; there are considerable uncertainties in this extrapolation. Direct study of those exposed to low doses does not produce any more precise information, although it does impose boundary conditions on the risk. Currently the most important problem in environmental radiation exposure is the increased incidence of childhood leukaemia observed around some nuclear installations; the explanation for this remains unclear. 相似文献
43.
Jennifer A. Sumner Natalie L. Colich Monica Uddin Don Armstrong Katie A. McLaughlin 《Neuropsychopharmacology》2019,85(3):268-278
Background
Recent conceptual models argue that early life adversity (ELA) accelerates development, which may contribute to poor mental and physical health outcomes. Evidence for accelerated development in youths comes from studies of telomere shortening or advanced pubertal development following circumscribed ELA experiences and neuroimaging studies of circuits involved in emotional processing. It is unclear whether all ELA is associated with accelerated development across global metrics of biological aging or whether this pattern emerges following specific adversity types.Methods
In 247 children and adolescents 8 to 16 years of age with wide variability in ELA exposure, we evaluated the hypothesis that early environments characterized by threat, but not deprivation, would be associated with accelerated development across two global biological aging metrics: DNA methylation (DNAm) age and pubertal stage relative to chronological age. We also examined whether accelerated development explained associations of ELA with depressive symptoms and externalizing problems.Results
Exposure to threat-related ELA (e.g., violence) was associated with accelerated DNAm age and advanced pubertal stage, but exposure to deprivation (e.g., neglect, food insecurity) was not. In models including both ELA types, threat-related ELA was uniquely associated with accelerated DNAm age (β = .18) and advanced pubertal stage (β = .28), whereas deprivation was uniquely associated with delayed pubertal stage (β = ?.21). Older DNAm age was related to greater depressive symptoms, and a significant indirect effect of threat exposure on depressive symptoms was observed through DNAm age.Conclusions
Early threat-related experiences are particularly associated with accelerated biological aging in youths, which may be a mechanism linking ELA with depressive symptoms. 相似文献44.
CJ Stewart ECL Marrs S Magorrian A Nelson C Lanyon JD Perry ND Embleton SP Cummings JE Berrington 《Acta paediatrica (Oslo, Norway : 1992)》2012,101(11):1121-1127
Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration. 相似文献
45.
Kirsten Sumner Louis C. Grandizio Samantha Schultz Joel C. Klena 《Hand (New York, N.Y.)》2021,16(1):99
Background: Defining an intraoperative radiographic view to best determine the radial styloid screw position in locked volar plating of distal radius fractures may improve fixation and aid in decreasing cortical penetration and implant complication. We used a cadaveric model to demonstrate a reproducible, oblique radiographic view to identify the radial styloid screw position. Methods: Nine fresh-frozen elbow-to-fingertip cadavers were used for this study. A 2.4-mm variable angle volar distal radius locking plate was applied to the distal radius. A Kirschner wire (K-wire) was inserted into the radial styloid through the plate. Placement of the K-wire through the tip of the styloid at the cortical edge was confirmed through a separate radial incision. A second K-wire was placed through the radius shaft into the ulna to aid in angular measurements. Live fluoroscopic imaging was used as the forearm was brought from full 90° of supination toward neutral. Once the K-wire was abutting the cortical edge, rotation ceased, and a goniometer was used to measure the angle of forearm rotation. This was repeated for a total of 3 repetitions on each specimen. Results: The average angle of supination best depicting the position of the radial styloid screw was 68.5° (range = 64.3°-70.5°). Conclusions: Radial styloid screw fixation in locked volar plating of distal radius fractures increases the ultimate strength to failure, but screw penetration and tendon irritation can occur. The 70° supinated oblique intraoperative view provides the most accurate evaluation of the position of the radial styloid screw. 相似文献
46.
47.
The first permanent molar (FPM) is commonly subject to significant compromise which may arise due to caries or endodontic complication, or from developmental anomalies such as hypoplasia. Compromised teeth with questionable prognosis may result in short and long-term clinical dilemmas. This review article highlights the factors that require careful consideration when a compromised FPM is detected and the importance of timely FPM extraction. Several clinical cases are described in detail to discuss possible treatment options from the orthodontic perspective. 相似文献
48.
The efficacy and outcome of bone marrow transplantation therapy following lethal irradiation were examined in syngeneic mice that had a hereditary macrocytic anemia (an/an) or were genotypically normal (+/+). Successful RBC and WBC replacement, based on blood cell parameters and donor genetic markers, were observed in all combinations of transplant therapy. Nevertheless, the an/an mice died prematurely several months after treatment, whether they received +/+ or an/an marrow cells. In contrast, the +/+ recipients of either +/+ or an/an marrow cells survived for at least 1 year after transplantation. Premature death of the an/an mice was associated with lymphopenia, anemia, kidney lesions, and severe pathogen-free pneumonitis. On the basis of our results, we hypothesize that the premature deaths of an/an mice are caused by a kind of chronic irradiation damage to which an/an mice are especially susceptible. 相似文献
49.
The widespread assumption that cytoplasts generated from human polymorphonuclear leukocytes (PMNs) are vesicles consisting solely of cytoplasm surrounded by plasma membrane and devoid of granule activity remains to be tested. PMN cytoplasts were prepared by centrifugation of intact cells on a Ficoll step gradient in the presence of cytochalasin B. Two granule membrane markers, Mol, a fluorometrically detectable antigen, and cytochrome b, both of which have been shown to translocate to the plasma membrane during granule release, were compared for their activity in cytoplasts and intact PMNs. We found that the amount of Mol detected on the plasma membrane of intact PMNs, as compared with other membrane markers (such as antigens LFA-1 and beta 2m), increased 1.6- fold upon exposure of PMNs to Ficoll plus cytochalasin B prior to centrifugation. Another twofold increase in Mol expression occurred upon cytoplast preparation. Release of the granule enzymes, vitamin B12- binding protein, and lysozyme were also followed and correlated well (r = .78 and .92) with the amount of Mol antigen present on the cell surface. Cytochrome b was also found to be higher (1.4-fold) on plasma membranes isolated from cytoplasts than on plasma membranes isolated from intact control cells. These results indicate that some fusion of granule membranes and plasma membranes occurred during treatment of PMNs with Ficoll plus cytochalasin b and during cytoplast preparation. 相似文献
50.
Talmadge JE; Schneider M; Keller J; Ruscetti F; Longo D; Pennington R; Bowersox O; Tribble H 《Blood》1989,73(6):1458-1467
In a series of studies designed to extend our understanding of interleukin-2 (IL-2) and to study the effect of biologic response modifiers on bone marrow, we observed that administering recombinant human (rH) IL-2 to normal mice resulted in an increase in the frequency of colony-forming units-culture (CFU-C) in bone marrow. In addition, rH IL-2 was able to accelerate host recovery from cyclophosphamide (CTX)- or radiation-induced bone marrow depression and peripheral blood leukopenia. Not only can rH IL-2 accelerate, in a dose-dependent manner, the return of bone marrow, peripheral blood cellularity, and CFU-C frequency to normal levels following cytoreduction by CTX or irradiation, but it also significantly increases CFU-C frequency to greater than normal levels. Furthermore, rH IL-2 can significantly prolong survival of animals receiving a lethal dose of irradiation or CTX. Thus, multiple mechanisms are responsible for the synergistic therapeutic activity associated with rH IL-2 and CTX. rH IL-2 does not act only as an immunomodulatory agent in the presence or absence of suppressor T cells, but also accelerates host recovery from cytoreductive agents, resulting in decreased leukopenia and perhaps resistances to secondary infection. Thus, rH IL-2 plus chemotherapy may increase therapeutic activity against neoplastic disease, not only by adding immune stimulation to the direct antitumor effect of the drug but also by allowing delivery of higher, more effective doses of chemotherapy. 相似文献