tbuckley/cabot-search huggingface dataset:
Breast-Feeding and Risk for Childhood Obesity
Authors: Elizabeth J. Mayer-Davis, Sheryl L. Rifas-Shiman, Li Zhou, Frank B. Hu, Graham A. Colditz, Matthew W. Gillman
Journal: Diabetes Care (2006)

OBJECTIVE— We sought to evaluate whether maternal diabetes or weight status attenuates a previously reported beneficial effect of breast-feeding on childhood obesity. RESEARCH DESIGN AND METHODS— Growing Up Today Study (GUTS) participants were offspring of women who participated in the Nurses’ Health Study II. In the present study, 15,253 girls and boys (aged 9–14 years in 1996) were included. Maternal diabetes and weight status and infant feeding were obtained by maternal self-report. We defined maternal overweight as BMI ≥25 kg/m2. Childhood obesity, from self-reported height and weight, was based on the Centers for Disease Control and Prevention definitions as normal, at risk for overweight, or overweight. Maternal status categories were nondiabetes/normal weight, nondiabetes/overweight, or diabetes. Logistic regression models used generalized estimating equations to account for nonindependence between siblings. RESULTS— For all subjects combined, breast-feeding was associated with reduced overweight (compared with normal weight) in childhood. Compared with exclusive use of formula, the odds ratio (OR) for exclusive breast-feeding was 0.66 (95% CI 0.53–0.82), adjusted for age, sex, and Tanner stage. Results did not differ according to maternal status (nondiabetes/normal weight OR 0.73 [95% CI 0.49–1.09]; nondiabetes/overweight 0.75 [0.57–0.99]; and diabetes 0.62 [0.24–1.60]). Further adjustment for potential confounders attenuated results, but results remained consistent across strata of maternal status (P value for interaction was 0.50). CONCLUSIONS— Breast-feeding was inversely associated with childhood obesity regardless of maternal diabetes status or weight status. These data provide support for all mothers to breast-feed their infants to reduce the risk for childhood overweight.
Incidence of perforated duodenal and gastric ulcer in Oxford.
Authors: R Sanders
Journal: Gut (1967)

EDITORIAL COMMENT A detailed study of particular value for comparison with other centres, it provides further evidence of the falling incidence of duodenal ulcer in Great Britain.In and around Oxford the incidence of perforated peptic ulcer was 14/100,000 in 1957 and in 1963 it was 7/100,000, the fall being due to duodenal and not to gastric ulcer.
Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial
Authors: Semira Manaseki-Holland, Zabihullah Maroof, Jane Bruce, M Zulf Mughal, Mohammad Isaq Masher, Zulfiqar A Bhutta, Gijs Walraven, Daniel Chandramohan
Journal: The Lancet (2012)
An immunoreactive theory of selective male affliction
Authors: Thomas Gualtieri, Robert E. Hicks
Journal: Behavioral and Brain Sciences (1985)

Abstract Males are selectively afflicted with the neurodevelopmental and psychiatric disorders of childhood, a broad and virtually ubiquitous phenomenon that has not received proper attention in the biological study of sex differences. The previous literature has alluded to psychosocial differences, genetic factors and elements pertaining to male “complexity” and relative immaturity, but these are not deemed an adequate explanation for selective male affliction. The structure of sex differences in neurodevelopmental disorders is hypothesized to contain these elements: (1) Males are more frequently afflicted, females more severely; (2) disorders arising in females are largely mediated by the genotype; in males, by a genotype by environment interaction; (3) complications of pregnancy and delivery occur more frequently with male births; such complications are decisive and influence subsequent development. We hypothesize that there is something about the male fetus that evokes an inhospitable uterine environment. This “evocative principle” is hypothesized to relate to the relative antigenicity of the male fetus, which may induce a state of maternal immunoreactivity, leading either directly or indirectly to fetal damage. The immunoreactive theory (IMRT) thus constructed is borrowed from studies of sex ratios and is the only explanation consistent with negative parity effects in the occurrence of pregnancy complications and certain neurodevelopmental disorders. Although the theory is necessarily speculative, it is heuristic and hypotheses derived from it are proposed; some are confirmed in the existing literature and by the authors' research.
mTORC1 is essential for leukemia propagation but not stem cell self-renewal
Authors: Takayuki Hoshii, Yuko Tadokoro, Kazuhito Naka, Takako Ooshio, Teruyuki Muraguchi, Naoyuki Sugiyama, Tomoyoshi Soga, Kimi Araki, Ken-ichi Yamamura, Atsushi Hirao
Journal: Journal of Clinical Investigation (2012)

Although dysregulation of mTOR complex 1 (mTORC1) promotes leukemogenesis, how mTORC1 affects established leukemia is unclear. We investigated the role of mTORC1 in mouse hematopoiesis using a mouse model of conditional deletion of Raptor, an essential component of mTORC1. Raptor deficiency impaired granulocyte and B cell development but did not alter survival or proliferation of hematopoietic progenitor cells. In a mouse model of acute myeloid leukemia (AML), Raptor deficiency significantly suppressed leukemia progression by causing apoptosis of differentiated, but not undifferentiated, leukemia cells. mTORC1 did not control cell cycle or cell growth in undifferentiated AML cells in vivo. Transplantation of Raptor-deficient undifferentiated AML cells in a limiting dilution revealed that mTORC1 is essential for leukemia initiation. Strikingly, a subset of AML cells with undifferentiated phenotypes survived long-term in the absence of mTORC1 activity. We further demonstrated that the reactivation of mTORC1 in those cells restored their leukemia-initiating capacity. Thus, AML cells lacking mTORC1 activity can self-renew as AML stem cells. Our findings provide mechanistic insight into how residual tumor cells circumvent anticancer therapies and drive tumor recurrence.
Cost of some types of prescribed drug can vary fourfold across England, audit shows
Authors: Adrian O'Dowd
Journal: BMJ (2007)

A meta-analysis of 42 trials of the type 2 diabetes drug rosiglitazone (Avandia) has shown a significantly raised risk of myocardial infarction and an increase in cardiovascular deaths that did not quite reach statistical significance (New England Journal of Medicine 2007 May 21 doi: 10.1056/ NEJMoa072761).The analysis by Steven Nissen and Kathy Wolski, of the Cleveland Clinic, Cleveland, Ohio, included 15 560 patients randomly assigned to regimens that included rosiglitazone, and 12 283 patients assigned to regimens that did not.The mean age of patients was 56 years, and the mean baseline glycated haemoglobin concentration was about 8.2%.Patients receiving rosiglitazone had an odds ratio for myocardial infarction of 1.43 (95% confidence interval 1.03 to 1.98, P=0.03).The odds ratio for death from cardiovascular causes was 1.64 (0.98 to 2.74, P=0.06).An editorial (doi: 10.1056/NEJMe078099) criticised the Food and Drug Administration for approving the drug on the basis of only its efficacy in glycaemic control in short term studies and also for a poor system for reporting adverse events after marketing.Bruce Psaty of the University of Washington in Seattle and Curt Furberg of Wake Forest University in Winston-Salem, North Carolina, also say that the Food and Drug Administration Revitalization Act, now moving through Congress, should be strengthened so that the FDA can follow a drug through its life cycle, with new emphasis on postmarketing.The FDA posted a safety alert on its website, cautioning patients taking the drug who have heart disease or are at high risk of a heart attack to talk to their doctors (www.fda.gov).GlaxoSmithKline said it "strongly disagrees" with the findings (www.gsk.com). Study links diabetes drug to heart deathsUK
Prostate Cancer: Score One for Validated Targets
Authors: Susan E. Bates
Journal: Clinical Cancer Research (2011)

This article is featured in Highlights of This Issue, [p. 3853][1]

This CCR Focus went to press shortly after the Food and Drug Administration (FDA) approval, on April 28, 2011, of abiraterone in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate
Maternal HIV Infection and Antibody Responses Against Vaccine-Preventable Diseases in Uninfected Infants
Authors: Christine E. Jones
Journal: JAMA (2011)

Altered immune responses might contribute to the high morbidity and mortality observed in human immunodeficiency virus (HIV)-exposed uninfected infants.To study the association of maternal HIV infection with maternal- and infant-specific antibody levels to Haemophilus influenzae type b (Hib), pneumococcus, Bordetella pertussis antigens, tetanus toxoid, and hepatitis B surface antigen.A community-based cohort study in Khayelitsha, Western Cape Province, South Africa, between March 3, 2009, and April 28, 2010, of 109 HIV-infected and uninfected women and their infants. Serum samples from 104 women and 100 infants were collected at birth and samples from 93 infants were collected at 16 weeks.Level of specific antibody in mother-infant pairs at delivery and in infants at 16 weeks, determined by enzyme-linked immunosorbent assays.At birth, HIV-exposed uninfected infants (n = 46) had lower levels of specific antibodies than unexposed infants (n = 54) did to Hib (0.37 [interquartile range {IQR}, 0.22-0.67] mg/L vs 1.02 [IQR, 0.34-3.79] mg/L; P < .001), pertussis (16.07 [IQR, 8.87-30.43] Food and Drug Administration [FDA] U/mL vs 36.11 [IQR, 20.41-76.28] FDA U/mL; P < .001), pneumococcus (17.24 [IQR, 11.33-40.25] mg/L vs 31.97 [IQR, 18.58-61.80] mg/L; P = .02), and tetanus (0.08 [IQR, 0.03-0.39] IU/mL vs 0.24 [IQR, 0.08-0.92] IU/mL; P = .006). Compared with HIV-uninfected women (n = 58), HIV-infected women (n = 46) had lower specific antibody levels to Hib (0.67 [IQR, 0.16-1.54] mg/L vs 1.34 [IQR, 0.15-4.82] mg/L; P = .009) and pneumococcus (33.47 [IQR, 4.03-69.43] mg/L vs 50.84 [IQR, 7.40-118.00] mg/L; P = .03); however, no differences were observed for antipertussis or antitetanus antibodies. HIV-exposed uninfected infants (n = 38) compared with HIV-unexposed infants (n = 55) had robust antibody responses following vaccination, with higher antibody responses to pertussis (270.1 [IQR, 84.4-355.0] FDA U/mL vs 91.7 [IQR, 27.9-168.4] FDA U/mL; P = .006) and pneumococcus (47.32 [IQR, 32.56-77.80] mg/L vs 14.77 [IQR, 11.06-41.08] mg/L; P = .001).Among South African infants, antenatal HIV exposure was associated with lower specific antibody responses in exposed uninfected infants compared with unexposed infants at birth, but with robust responses following routine vaccination.
Structure‐guided design affirms inhibitors of hepatitis C virus p7 as a viable class of antivirals targeting virion release
Authors: Toshana L. Foster, Gary S. Thompson, Arnout P. Kalverda, Jayakanth Kankanala, Matthew Bentham, Laura F. Wetherill, Joseph Thompson, Amy M. Barker, Dean Clarke, Marko Noerenberg, Arwen R. Pearson, David J. Rowlands, Steven W. Homans, Mark Harris, Richard Foster, Stephen Griffin
Journal: Hepatology (2013)

Current interferon-based therapy for hepatitis C virus (HCV) infection is inadequate, prompting a shift toward combinations of direct-acting antivirals (DAA) with the first protease-targeted drugs licensed in 2012. Many compounds are in the pipeline yet primarily target only three viral proteins, namely, NS3/4A protease, NS5B polymerase, and NS5A. With concerns growing over resistance, broadening the repertoire for DAA targets is a major priority. Here we describe the complete structure of the HCV p7 protein as a monomeric hairpin, solved using a novel combination of chemical shift and nuclear Overhauser effect (NOE)-based methods. This represents atomic resolution information for a full-length virus-coded ion channel, or "viroporin," whose essential functions represent a clinically proven class of antiviral target exploited previously for influenza A virus therapy. Specific drug-protein interactions validate an allosteric site on the channel periphery and its relevance is demonstrated by the selection of novel, structurally diverse inhibitory small molecules with nanomolar potency in culture. Hit compounds represent a 10,000-fold improvement over prototypes, suppress rimantadine resistance polymorphisms at submicromolar concentrations, and show activity against other HCV genotypes. This proof-of-principle that structure-guided design can lead to drug-like molecules affirms p7 as a much-needed new target in the burgeoning era of HCV DAA.
Duplication of the Inferior Vena Cava and Its Role in Recurrent Pulmonary Emboli
Authors: Marvin Wagner
Journal: JAMA (1969)

Recurrent thromboembolism occurred in a 67-year-old man and an inferior caval ligation was performed. Phlebography showed a supplementary left vena cava. A secondary left caval ligation was performed and the patient had an uneventful recovery and no further incident.
Alloantigen persistence in induction and maintenance of transplantation tolerance.
Authors: S Morecki, B Leshem, A Eid, S Slavin
Journal: The Journal of Experimental Medicine (1987)

Infusion of parental bone marrow cells into F1 hybrids conditioned by total lymphoid irradiation (TLI) results in chimeras with a high percentage of donor-type cells, and without clinical signs of graft-vs.-host reaction. In these chimeras, a state of tolerance has been shown to be associated with paucity of cytotoxic T lymphocyte percursors (pCTL) reactive with host-type alloantigens. To determine whether the presence of tolerizing alloantigens is essential for maintenance of unresponsiveness, lymphohematopoietic cells obtained from such tolerant chimeras were transferred into supralethally irradiated recipients of two different genotypes: in one case the adoptive recipients were syngeneic with host-type cells, and in the other they were syngeneic with donor-type cells of the original chimeras, thus providing the chimeric cells with a tolerogen-free environment. After "parking" for 4 d in syngeneic donor-type mice, the transferred cells displayed a marked increase in the frequency of pCTL directed against tolerizing alloantigens, whereas a low pCTL frequency directed against the same H-2 target cells was maintained in allogeneic tolerizing-type adoptive recipients. Multiple injections of adoptive donor-type mice with tolerizing-type cells of the original chimera reestablished a low level of cytotoxic precursors. Cytotoxic activity against unrelated alloantigens was independent of the presence of tolerogen-presenting cells in the adoptively transferred mice. Our experimental model suggests that persistence of cells bearing tolerizing alloantigens is an essential requirement for maintenance of previously established tolerance.
Tangier Disease
Authors: Ernst J. Schaefer, Linda L. Kay, Loren A. Zech, H. Bryan Brewer
Journal: Journal of Clinical Investigation (1982)

Tangier disease is a rare familial disorder characterized by enlarged orange tonsils, transient peripheral neuropathy, hepatosplenomegaly, and lymphadenopathy, as well as striking reductions in plasma high density lipoproteins (HDL) and their major protein constituents, apolipoproteins (apo)A-I and A-II. In order to test the hypothesis that Tangier patients have abnormal apoA-I or apoA-II, the in vitro lipoprotein binding and in vivo metabolic characteristics of these proteins isolated from normal and Tangier plasma, were studied in normal subjects and patients with Tangier disease. After incubation with normal plasma, significantly greater percentages of radiolabeled Tangier apoA-I were associated with the 1.063-g/ml supernate (6%) and the 1.21 g/ml infranate (19%), and a lower percentage with HDL (75%), than those observed for normal apoA-I (2, 8, and 90%, respectively). In contrast, the lipoprotein binding properties of normal and Tangier apoA-II were very similar. Following the injection of radiolabeled normal and Tangier apoA-I into normal subjects (n = 4), the mean residence times of the specific activity for apoA-I(Tangier) were significantly lower, both in plasma (1.29 d) and in HDL (1.34 d), than those observed for normal apoA-I (3.80 and 4.06 d). In Tangier homozygotes the decay rates of these tracers were very rapid and were similar. No significant differences between the kinetics of normal and Tangier apoA-II were observed in normal subjects (n = 2). Tangier homozygotes (n = 3) had mean plasma HDL cholesterol, apoA-I, and apoA-II concentrations that were 4, 2, and 11% of normal (n = 24), respectively, whereas for heterozygotes (n = 3) these values were 46, 62, and 68% of normal. In homozygotes, in contrast to normals or heterozygotes, a significant fraction of both apoA-I and apoA-II were found in the 1.063-g/ml supernate instead of in HDL. Homozygotes had apoA-I(Tangier) synthesis rates and residence times that were 41 and 5% of values observed for normal apoA-I in normal subjects, and for apoA-II in homozygotes, these parameters were 63 and 18% of normal. Heterozygotes had apoA-I synthesis rates and residence times that were 92 and 66% of normal, and for apoA-II these values were 101 and 64% of normal. These data are consistent with the concept that apoA-I(Tangier) is functionally and metabolically distinct from normal apoA-I, and is the cause of the striking hypercatabolism of apoA-I and apoA-II, and the lipoprotein abnormalities observed in Tangier disease.
The Influence of Injection Site upon the Form of Dye-Dilution Curves
Authors: MORTON LEE PEARCE, WILLIAM P. McKEEVER, PHILIP DOW, ELLIOT V. NEWMAN
Journal: Circulation Research (1953)

The validity of the serial compartment analysis of dye dilution curves was tested by injecting dye into the right auricle, pulmonary artery, a pulmonary vein and the aorta consecutively while sampling blood from the carotid artery. It was found that the serial compartment analogy is valid and that the lungs are the largest volume in the series. In curves obtained by injecting into the pulmonary artery and sampling from the left auricle it was shown that under the conditions of the experiments, the lungs act like a single volume from which dye is washed out in exponential fashion.
Intussusception Risk after Rotavirus Vaccination in U.S. Infants
Authors: W. Katherine Yih, Tracy A. Lieu, Martin Kulldorff, David Martin, Cheryl N. McMahill-Walraven, Richard Platt, Nandini Selvam, Mano Selvan, Grace M. Lee, Michael Nguyen
Journal: New England Journal of Medicine (2014)

International postlicensure studies have identified an increased risk of intussusception after vaccination with the second-generation rotavirus vaccines RotaTeq (RV5, a pentavalent vaccine) and Rotarix (RV1, a monovalent vaccine). We studied this association among infants in the United States.The study included data from infants 5.0 to 36.9 weeks of age who were enrolled in three U.S. health plans that participate in the Mini-Sentinel program sponsored by the Food and Drug Administration. Potential cases of intussusception and vaccine exposures from 2004 through mid-2011 were identified through procedural and diagnostic codes. Medical records were reviewed to confirm the occurrence of intussusception and the status with respect to rotavirus vaccination. The primary analysis used a self-controlled risk-interval design that included only vaccinated children. The secondary analysis used a cohort design that included exposed and unexposed person-time.The analyses included 507,874 first doses and 1,277,556 total doses of RV5 and 53,638 first doses and 103,098 total doses of RV1. The statistical power for the analysis of RV1 was lower than that for the analysis of RV5. The number of excess cases of intussusception per 100,000 recipients of the first dose of RV5 was significantly elevated, both in the primary analysis (attributable risk, 1.1 [95% confidence interval, 0.3 to 2.7] for the 7-day risk window and 1.5 [95% CI, 0.2 to 3.2] for the 21-day risk window) and in the secondary analysis (attributable risk, 1.2 [95% CI, 0.2 to 3.2] for the 21-day risk window). No significant increase in risk was seen after dose 2 or 3. The results with respect to the primary analysis of RV1 were not significant, but the secondary analysis showed a significant risk after dose 2.RV5 was associated with approximately 1.5 (95% CI, 0.2 to 3.2) excess cases of intussusception per 100,000 recipients of the first dose. The secondary analysis of RV1 suggested a potential risk, although the study of RV1 was underpowered. These risks must be considered in light of the demonstrated benefits of rotavirus vaccination. (Funded by the Food and Drug Administration.).
Smoking and Other Risk Factors for Lung Cancer in Women&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: A H Wu, B E Henderson, M C Pike, M C Yu
Journal: JNCI Journal of the National Cancer Institute (1985)

A case-control study among white women in Los Angeles County was conducted to investigate the role of smoking and other factors in the etiology of lung cancer in women. A total of 149 patients with adenocarcinoma (ADC) and 71 patients with squamous cell carcinoma (SCC) of the lung and their age- and sex-matched controls were interviewed. Personal cigarette smoking accounted for almost all of SCC and about half of ADC in this study population. Among nonsmokers, slightly elevated relative risk(s) (RR) for ADC were observed for passive smoke exposure from spouse(s) [RR = 1.2; 95% confidence interval (CI)= 0.5, 3.3] and at work (RR = 1.3; 95% Cl = 0.5, 3.3). Childhood pneumonia (RR = 2.7; 95% Cl = 1.1, 6.7) and childhood exposure to coal burning (RR = 2.3; 95% Cl = 1.0, 5.5) were additional risk factors for ADC. For both ADC and SCC, increased risks were associated with decreased intake of β-carotene foods but not for total preformed vitamin A foods and vitamin supplements.
Mitoxantrone: A New Anticancer Drug with Significant Clinical Activity
Authors: TODD D. SHENKENBERG
Journal: Annals of Internal Medicine (1986)

Clinical studies using mitoxantrone, an anthraquinone, were begun in the United States in 1979. Subsequent phase II and III trials have shown that mitoxantrone has significant clinical activity in patients with breast cancer, acute leukemia, and lymphoma. The drug has antiviral, antibacterial, antiprotozoal, immunomodulating, and antineoplastic properties and is mutagenic in some animal systems. Its mechanism of action seems to involve both DNA intercalation and nonintercalative electrostatic interactions. The dose-limiting toxicity is myelosuppression when the drug is given on a single-dose, every-3-week schedule and mucositis when it is given daily for 5 days. Other toxicities include gastrointestinal and cardiac effects, the gastrointestinal toxicity being less severe and less frequent than that with the anthracycline anticancer drugs. Because of its low incidence of serious toxicities and effectiveness in treating certain solid tumors and leukemias, mitoxantrone is a promising new agent in the treatment of cancer.