bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Definitive Severe Mitochondrial Signs and Symptoms among Deceased HIV‐Uninfected and HIV‐Indeterminate Children ≤ 5 Years of Age, Pediatric Spectrum of HIV Disease Project (PSD), USA
Authors: DOMINGUEZ K. , BERTOLLI J. , FOWLER M. , PETERS V. , ORTIZ I. , MELVILLE S. , RAKUSAN T. , FREDERICK T. , HSU H. , D'ALMADA P. , MALDONADO Y. , WILFERT C. ,   THE PSD CONSORTIUM, AND THE PERINATAL SAFETY REVIEW WORKING GROUP
Published: July 2010

Abstract: Background: In response to recent reports of mitochondrial dysfunction in HIV‐uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV‐exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort.Methods: Hospitalization, clinic and death records for deceased HIV‐uninfected and HIV‐indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category.Results: 8,465 of 13,125 HIV‐exposed children were either HIV‐uninfected or HIV‐indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV‐uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV‐indeterminate children who were classified in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV‐uninfected and HIV‐indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure.Conclusion: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi‐site prospective cohort studies of HIV‐exposed children is essential in the era of highly active antiretroviral therapy.
Genetic Instability in Epithelial Tissues at Risk for Cancer
Authors: HITTELMAN WALTER N. 
Published: July 2010

AbstractEpithelial tumors develop through a multistep process driven by genomic instability frequently associated with etiologic agents such as prolonged tobacco smoke exposure or human papilloma virus (HPV) infection. The purpose of the studies reported here was to examine the nature of genomic instability in epithelial tissues at cancer risk in order to identify tissue genetic biomarkers that might be used to assess an individual's cancer risk and response to chemopreventive intervention. As part of several chemoprevention trials, biopsies were obtained from risk tissues (i.e., bronchial biopsies from chronic smokers, oral or laryngeal biopsies from individuals with premalignancy) and examined for chromosome instability using in situ hybridization. Nearly all biopsy specimens show evidence for chromosome instability throughout the exposed tissue. Increased chromosome instability was observed with histologic progression in the normal to tumor transition of head and neck squamous cell carcinomas. Chromosome instability was also seen in premalignant head and neck lesions, and high levels were associated with subsequent tumor development. In bronchial biopsies of current smokers, the level of ongoing chromosome instability correlated with smoking intensity (e.g., packs/day), whereas the chromosome index (average number of chromosome copies per cell) correlated with cumulative tobacco exposure (i.e., pack‐years). Spatial chromosome analyses of the epithelium demonstrated multifocal clonal outgrowths. In former smokers, random chromosome instability was reduced; however, clonal populations appeared to persist for many years, perhaps accounting for continued lung cancer risk following smoking cessation.
Mechanisms of Hormonal Prevention of Breast Cancer
Authors: MEDINA DANIEL , SIVARAMAN LAKSHMI , HILSENBECK SUSAN G. , CONNEELY ORLA , GINGER MELANIE , ROSEN JEFFREY , O'MALLEY BERT W. 
Published: July 2010

AbstractReproductive history is a consistent risk factor for human breast cancer. Epidemiological studies have repeatedly demonstrated that early age of first pregnancy is a strong protective factor against breast cancer and provides a physiologically operative model to achieve a practical mode of prevention. In rodents, the effects of full‐term pregnancy can be mimicked by a three‐week exposure to low doses of estrogen and progesterone. Neither hormone alone is sufficient to induce protection. The cellular and molecular mechanisms that underlie hormone‐induced refractoriness are largely unresolved. Our recent studies have demonstrated that an early cellular response that is altered in hormone‐treated mammary cells is the initial proliferative burst induced by the chemical carcinogen methylnitrosourea. The decrease in proliferation is also accompanied by a decrease in the ability of estrogen receptor‐positive cells to proliferate. RNA expression of several mammary cell‐cycle‐related genes is not altered in hormone‐treated mice; however, immunohistochemical assays demonstrate that the protein level and nuclear compartmentalization of the p53 tumor suppressor gene are markedly upregulated as a consequence of hormone treatment. These results support the hypothesis that hormone stimulation, at a critical period in mammary development, results in cells with persistent changes in the intracellular regulatory loops governing proliferation and response to DNA damage. A corollary to this hypothesis is that the genes affected by estrogen and progesterone are independent of alveolar differentiation‐specific genes. Suppressive subtractive hybridization‐PCR methods have identified several genes that are differentially expressed as a consequence of prior estrogen and progesterone treatment. Future experiments are aimed at determining the mechanisms of hormone‐induced upregulation of p53 protein expression as part of the overall goal of identifying and functionally characterizing the genes responsible for the refractory phenotype.
Beyond Tamoxifen
Authors: FABIAN CAROL J. , KIMLER BRUCE F. 
Published: July 2010

AbstractAlthough tamoxifen appears to markedly reduce breast cancer risk in women with a prior diagnosis of atypical hyperplasia orin situcarcinoma, it is not clear what other groups of women receive substantial benefit. Major breast chemoprevention priorities are to (1) develop new agents that (a) have fewer side effects, (b) are effective in ER− as well as tamoxifen‐resistant precancerous tissue, and (c) are compatible with hormone therapy; and (2) develop efficient clinical strategies including prognostic and predictive morphologic and molecular biomarkers. Breast tissue may be repeatedly sampled for evidence of intraepithelial neoplasia by fine needle aspiration, ductal lavage, or needle biopsy to select candidates at highest short‐term risk as well as to monitor response in small proof of principle studies prior to a large cancer incidence trial. Molecular marker expression may also be used to select a cohort most likely to respond to a particular agent. A large number of new agents are attractive as potential prevention agents and some are already in clinical prevention testing. Compounds which should be effective in ER+ precancerous tissue but may have a better side‐effect profile include new selective estrogen receptor modulators which lack uterine estrogen agonist activity, isoflavones, aromatase inactivators/inhibitors for postmenopausal women, and gonadotropin‐releasing hormone regimens for premenopausal women. Retinoids, rexinoids, and deltanoids may be efficacious in ER+ tissue resistant to tamoxifen. Agents which should theoretically have activity in ER− or ER+ precancerous tissue include polyamine synthesis inhibitors, tyrosine kinase inhibitors, combined demethylating agents and histone deacetylase inhibitors, as well as metalloprotease and angiogenesis inhibitors. Sample Phase I and Phase II clinical trial designs are reviewed using modulation of molecular markers and breast intraepithelial neoplasia as the major endpoints.
Chemoprevention with Antiestrogens: The Beginning of the End for Breast Cancer
Authors: JORDAN V. CRAIG 
Published: July 2010

AbstractIn the 1960s, compounds known as nonsteroidal antiestrogens were identified as potential contraceptives, but the drugs caused the induction of ovulation in subfertile women. Tamoxifen and clomiphene were marketed for this indication. However, tamoxifen was advanced for the treatment of breast cancer in the 1970s through a close cooperation between the laboratory and the clinical trials community. The extensive use of long‐term adjuvant tamoxifen has resulted in saving the lives of 400,000 women with breast cancer. Tamoxifen is a selective estrogen receptor modulator (SERM) that produces antiestrogenic actions in the breast but estrogen‐like actions in bone and lowers serum cholesterol. These properties not only allowed the application of tamoxifen as the first chemopreventive in high‐risk pre‐ and postmenopausal women but also the development of raloxifene to prevent osteoporosis with the potential to prevent breast cancer in postmenopausal women. The future development of SERMs holds the promise of preventing osteoporosis and coronary heart disease as well as breast and endometrial cancer.
Cellular Mechanisms of Calcium and Vitamin D in the Inhibition of Colorectal Carcinogenesis
Authors: LAMPRECHT SERGIO A. , LIPKIN MARTIN 
Published: July 2010

AbstractConvincing evidence is available showing that dietary calcium and vitamin D impede the development of colonic carcinogenesis. The major cellular modes of action of calcium and vitamin D which can contribute to the inhibition of colonic neoplasia are reviewed in this article. These consist of complex series of signaling events induced by the chemopreventive agents acting at various tiers of colonic cell organization.
The Future of Colon Cancer Prevention
Authors: UMAR ASAD , VINER JAYE L. , HAWK ERNEST T. 
Published: July 2010

AbstractChemoprevention science is in flux owing to rapid advances in postgenomic technology. We have witnessed enormous advances in the areas of early detection and molecular profiling of colorectal carcinogenesis; however, unique interpretive and technologic challenges persist. Neoplastic hallmarks must be iteratively tested and validated as markers of risk, targets for intervention, and/or markers of response in order to expedite the development of preventive interventions. In this review, we highlight several of the technologies that are revolutionizing our understanding of carcinogenesis and our approach to colorectal cancer prevention.
Inhibition of Cyclooxygenase‐2
Authors: DANNENBERG ANDREW J. , ALTORKI NASSER K. , BOYLE JAY O. , LIN DERRICK T. , SUBBARAMAIAH KOTHA 
Published: July 2010

AbstractMultiple lines of evidence suggest that cyclooxygenase‐2 (COX‐2), an inducible form of COX, represents a potential pharmacologic target to prevent cancer. Key data suggesting a causal relationship between increased COX‐2 activity and carcinogenesis and possible mechanisms of action of COX‐2 in this context will be discussed. The possibility that COX‐2 represents a pharmacological target for preventing upper aerodigestive cancers (head and neck, lung) will be emphasized. Importantly, clinical trials have been initiated to assess the chemopreventive properties of selective COX‐2 inhibitors.
Diet and Breast Cancer Surveillance Behaviors among Harlem Women
Authors: GORIN SHERRI SHEINFELD , JACOBSON JUDITH 
Published: July 2010

AbstractThe consumption of green, yellow, and other vegetables, fruits and fruit juices may be protective against breast cancer, and, alongside regular breast cancer screening, may contribute to ethnic and racial differences in breast cancer rates. The purpose of this study is to assess the dietary and sociodemographic predictors of surveillance among Harlem women, using a population‐based household survey. One half of the Harlem women in this sample consumed no or one fruit or vegetable per day. Logistic regression analyses revealed that women who consumed more fruits and vegetables had received more recent mammography, and that women who were unemployed were less likely to receive recent breast cancer screening than were those who worked full‐ or part‐time. The high response rate and the representativeness of the sample are study strengths. Owing to the small sample size for women between 40‐65, the ages for which screening mammography and clinical breast exam are recommended, subgroup analyses were limited. Therefore, additional study of age‐adjusted dietary patterns and screening among African American women is suggested.
Chemopreventive Agents Inhibit Aberrant Proliferation of the Aneuploid Phenotype in a Colon Epithelial Cell Line Established from Apc 1638N [+/−] Mouse
Authors: KATDARE MEENA , KOPELOVICH LEVY , TELANG NITIN 
Published: July 2010

AbstractLoss of function of the adenomatous polyposis coli (APC) tumor suppressor gene predisposes for familial adenomatous polyposis (FAP) syndrome. The Apc gene knockout mice exhibit accelerated intestinal carcinogensis modifiable by diverse pharmacological agents. Present experiments utilized the Apc[+/−] 1638N COL colon epithelial cell line (origin: histologically normal colon) as the model. Retinoid receptor modulator 9‐cis‐retinoic acid (9‐cis‐RA), ornithine decarboxylase inhibitor difluoromethyl ornithine (DFMO), and nonselective cyclooxygenase inhibitor sulindac (SUL) represented the chemopreventive test compounds. Population doubling, cell cycle progression, and anchorage‐independent growth provided mechanistic end points for chemopreventive efficacy. Treatment of 1638N COL cells with 9‐cis‐RA, DFMO and SUL produced a dose‐dependent cytostatic growth arrest by decreasing the number of population doublings and altering aneuploid G0/G1: S+G2/M ratio. The clonally expanded 1638N‐Cl1 cells selected for anchorage‐independent growth exhibited decreased anchorage‐independent colony formation in response to treatment with the three test compounds. Susceptibility of preneoplastic 1638N COL cells to mechanistically distinct chemopreventive agents validates a unique epithelial cell culture model for FAP syndrome, and facilitates investigations on Apc regulated colon carcinogenesis and cancer prevention.
The Effect of High Doses of Folic Acid on the Overexpression of Ornithine Decarboxylase and S‐Adenosylmethionine Content in Human Colon Adenomatous Polyps
Authors: BUKIN YU. V. , DRAUDIN‐KRYLENKO V. A. , LEVCHUK A. A. , PODDUBNIY B. K. , MAZUROV S. T. 
Published: July 2010

AbstractIt was shown that the 3‐month supplementation of patients having colon polyps with folic acid (5 mg/day) led to a 35% decrease in abnormally high ornithine decarboxylase activity in polyps that was accompanied by a 43% increase of S‐adenosylmethionine content in polyps.
Embryo Effects in Human Implantation
Authors: SIMÓN CARLOS , DOMINGUEZ FRANCISCO , REMOHÍ JOSÉ , PELLICER ANTONIO 
Published: July 2010

AbstractEmbryonic implantation requires coordinated development of the blastocyst and the maternal endometrium. Considerable advances have been made in the understanding of the cell biology of human embryo and maternal endometrium as separate entities. Nevertheless, communication between them and their reciprocal effects on each other constitute an exciting and as‐yet unsolved problem in reproductive medicine. Cross‐talk among the embryo, endometrium, and the corpus luteum are known to occur in ruminants and primates; more specifically, endometrial‐embryonic interactions have been reported in rodents and primates. Here, we present updated information in humans on the embryonic regulation of endometrial epithelial molecules such as chemokines, adhesion molecules, antiadhesion molecules, and leptin during the apposition and adhesion phases of human implantation. Also the embryonic induction of apoptosis in endometrial epithelial cells as a mechanism for crossing the epithelial barrier will be described.
Maternal‐Embryonic Cross‐Talk
Authors: HILL JOSEPH A. 
Published: July 2010

AbstractThe human menstrual cycle evolved to prepare the uterus for blastocyst implantation, which is fundamentally under the control of gonadal steroids. Ovarian hormones induce marked morphological, physiological, and biochemical changes within reproductive tissues. These changes in turn induce alterations in the biosynthetic activity and release of a myriad of locally produced proteins into the microenvironment of the reproductive tract. These same factors may be further modified by proteins secreted by the developing embryo and accompanying cumulus cells in intimate contact with reproductive epithelium in a network signaling process. Communication is not one‐way, but rather maternal‐embryonic cross‐talk may occur as maternal proteins are secreted into the microenvironment of the oviduct and uterus, facilitating fertilization and early embryo development and serving as homing beacons for blastocyst nidation. The communicating language facilitating this dialogue includes cytokines, growth factors, angiogenic factors, apoptotic factors, adhesion molecules, and, potentially, homeotic genes.
Role of Steroid Hormone‐Regulated Genes in Implantation
Authors: BAGCHI INDRANI C. , LI QUANXI , CHEON YONG PIL 
Published: July 2010

AbstractThe endometrium acquires the ability to implant the developing embryo within a specific time window, termed the “receptive phase.” During this period, the endometrium undergoes pronounced structural and functional changes induced by the ovarian steroids, estrogen and progesterone, which prepare it to be receptive to invasion by the embryo. These steroid‐induced molecules, when identified, may serve as useful markers of uterine receptivity. In this article, we provide a brief description of one such molecule that has emerged as candidate marker of steroid hormone action in rats and humans during implantation.
Laparoscopic Myomectomy
Authors: DUBUISSON JEAN‐BERNARD , CHAPRON CHARLES , FAUCONNIER ARNAUD , BABAKI‐FARD KATAYOUN 
Published: July 2010

AbstractThe appearance of uterine myomas has been linked to infertility. It has been suggested that surgical management of myomas by laparoscopic myomectomy improves fertility rates in these group of patients. In this paper we initially describe specific aspects of the surgical technique of laparoscopic myomectomy including the set‐up, precise technique for hysteroromy, enucleation of the myoma, suturing of the uterus, and extraction of the myoma. We detail recent findings that demonstrate improved fertility rates in women undergoing laparoscopic myomectomy. We recommend that, when criteria for selection of patients is strictly adhered to and patients present with no other associated infertility, laparoscopic myomectomy be used to increase the implantation rate.
Management of Deep Endometriosis
Authors: CHAPRON CHARLES , DUBUISSON JEAN‐BERNARD 
Published: July 2010

AbstractDeep endometriosis is defined as an endometriotic lesion that penetrates the retroperitoneal space for a distance of ≥5 mm. Deep endometriosis is extremely active, occurs in phase with eutopic endometrium, evolves progressively with age, and is most often located in the pouch of Douglas, the rectovaginal septum, the uterosacral ligaments, and occasionally in the uterovesical fold. These lesions are associated with pelvic pain, the intensity of which is proportional to the depth of penetration. It is clear that choice of treatment depends on the location of the endometriotic lesion. In this paper we describe our methods for the initial diagnosis and subsequent treatment of deep endometriosis. These include consultation and clinical examination protocols, use of rectal endoscopic ultrasonography (EUS), magnetic resonance imaging (MRI), and transvaginal ultrasonography techniques in diagnosis and surgical treatment approaches.
Cancer and Pregnancy
Authors: CREASMAN WILLIAM T. 
Published: July 2010

AbstractCarcinoma of the cervix is the most frequently diagnosed cancer in pregnancy. Still, it is an unusual situation. An abnormal Pap smear during pregnancy is a much more common occurrence and fortunately one that can be managed conservatively. Although definitive treatment for intraepithelial disease can be delayed until the postpartum period, diagnostic evaluation should be done when the abnormal Pap smear is present. Invasive cancer management is dependent on gestational age of the fetus. Pregnancy affords an excellent opportunity to screen for cervical neoplasia.
Are Changes of the Cell Membrane Structure Causally Involved in the Aging Process?
Authors: SPITELLER GERHARD 
Published: July 2010

AbstractLipid peroxidation is recognized by proliferation, wounding, and aging. The connecting link between these different events is a change in cell wall structure, which activates membrane bound phospholipases. These cleave phospholipids. Thus liberated polyunsaturated fatty acids (PUFAs) are substrates for lipoxygenases, which accept equally well linoleic acid and arachidonic acid and generate lipid hydroperoxides (LOOHs). If the amount of free PUFAs exceeds a certain amount, lipoxygenases commit suicide. The consequence is liberation of free iron ions that react with LOOHs by formation of radicals. These start a chain reaction. LOO• radicals produced in the course of this process attack proteins, nucleic acids, and also double bonds of all unsaturated compounds by epoxidation. Morever LOOHs are decomposed to toxic epoxy acids and αβγδ‐unsaturated aldehydes. Both species react with glutathione. The resulting products seem to induce apoptosis. Since the products generated by wounding or aging are formed by decomposition of LOOHs the investigation of the aging processes can be simplified by studying the physiological action of artificially generated lipid peroxidation products derived from pure PUFAs. Degradation products of LOOHs are generated by thermal decompositon of fat‐containing PUFAs. These products are induced into the body by adsorption in the intestine. They are at least partly incorporated in low density lipoproteins (LDLs). Primarily investigations seem to indicate that an overload of a diet rich in PUFAs induces only after two days an increase in oxidized LDL/PUFAs for a factor up to two in young people and for a factor of more than two in old individuals.