tbuckley/cabot-search huggingface dataset:
Intake of Carotenoids and Retino in Relation to Risk of Prostate Cancer
Authors: E. Giovannucci, A. Ascherio, E. B. Rimm, M. J. Stampfer, G. A. Colditz, W. C. Willett
Journal: JNCI Journal of the National Cancer Institute (1995)

Background : Several human studies have observed a direct association between retinol (vitamin A) intake and risk of prostate cancer; other studies have found either an inverse association or no association of intake of β-carotene (the major provitamin A) with risk of prostate cancer. Data regarding carotenoids other than β-carotene in relation to prostate cancer risk are sparse. Purpose : We conducted a prospective cohort study to examine the relationship between the intake of various carotenoids, retinol, fruits, and vegetables and the risk of prostate cancer. Methods : Using responses to a validated, semiquantitative food-frequency questionnaire mailed to participants in the Health Professionals Follow-up Study in 1986, we assessed dietary intake for a 1-year period for a cohort of 47 894 eligible subjects initially free of diagnosed cancer. Follow-up questionnaires were sent to the entire cohort in 1988, 1990, and 1992. We calculated the relative risk (RR) for each of the upper categories of intake of a specific food or nutrient by dividing the incidence rate of prostate cancer among men in each of these categories by the rate among men in the lowest intake level. All P values resulted from two-sided tests. Results : Between 1986 and 1992, 812 new cases of prostate cancer, including 773 non-stage A1 cases, were documented. Intakes of the carotenoids β-carotene, α-carotene, lutein, and β-cryp-toxanthin were not associated with risk of non-stage A1 prostate cancer; only lycopene intake was related to lower risk (age- and energy-adjusted RR = 0.79; 95% confidence interval [CI] = 0.64–0.99 for high versus low quintile of intake; P for trend =.04). Of 46 vegetables and fruits or related products, four were significantly associated with lower prostate cancer risk; of the four— tomato sauce (P for trend =.001), tomatoes (P for trend =.03), and pizza (P for trend =.05), but not strawberries— were primary sources of lycopene. Combined intake of tomatoes, tomato sauce, tomato juice, and pizza (which accounted for 82% of lycopene intake) was inversely associated with risk of prostate cancer (multivariate RR = 0.65; 95% CI = 0.44–0.95, for consumption frequency greater than 10 versus less than 1.5 servings per week; P for trend =.01) and advanced (stages C and D) prostate cancers (multivariate RR = 0.47; 95% CI = 0.22–1.00; P for trend =.03). No consistent association was observed for dietary retinol and risk of prostate cancer. Conclusions : These findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk, but other measured carotenoids are unrelated to risk. Implications : Our findings support recommendations to increase vegetable and fruit consumption to reduce cancer incidence but suggest that tomato-based foods may be especially beneficial regarding prostate cancer risk.
THE MATERNAL TRANSMISSION OF VACCINIAL IMMUNITY IN SWINE
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1934)

The protective substances produced by vaccinia virus in swine are transmitted repeatedly to the young by way of the colostrum of the sow. In 2 instances suckling immunity was demonstrable in the young of 6 successive farrowings which numbered 37 and 57 individuals, respectively. The immunity acquired by suckling began to decline during the 2nd month and was practically negligible by the end of the 3rd month. Vaccinia virus introduced cutaneously during the first few days of life in the passively protected pigs exerted little or no immunizing effect.
Monitoring Photosensitizer Uptake Using Two Photon Fluorescence Lifetime Imaging Microscopy
Authors: Shu-Chi Allison Yeh, Kevin R. Diamond, Michael S. Patterson, Zhaojun Nie, Joseph E. Hayward, Qiyin Fang
Journal: Theranostics (2012)

Photodynamic Therapy (PDT) provides an opportunity for treatment of various invasive tumors by the use of a cancer targeting photosensitizing agent and light of specific wavelengths. However, real-time monitoring of drug localization is desirable because the induction of the phototoxic effect relies on interplay between the dosage of localized drug and light. Fluorescence emission in PDT may be used to monitor the uptake process but fluorescence intensity is subject to variability due to scattering and absorption; the addition of fluorescence lifetime may be beneficial to probe site-specific drug-molecular interactions and cell damage. We investigated the fluorescence lifetime changes of Photofrin(®) at various intracellular components in the Mat-LyLu (MLL) cell line. The fluorescence decays were analyzed using a bi-exponential model, followed by segmentation analysis of lifetime parameters. When Photofrin(®) was localized at the cell membrane, the slow lifetime component was found to be significantly shorter (4.3 ± 0.5 ns) compared to those at other locations (cytoplasm: 7.3 ± 0.3 ns; mitochondria: 7.0 ± 0.2 ns, p < 0.05).
Complementary Signaling through flt3 and Interleukin-7 Receptor α Is Indispensable for Fetal and Adult B Cell Genesis
Authors: Ewa Sitnicka, Cord Brakebusch, Inga-Lill Martensson, Marcus Svensson, William W. Agace, Mikael Sigvardsson, Natalija Buza-Vidas, David Bryder, Corrado M.Cilio, Henrik Ahlenius, Eugene Maraskovsky, Jacques J. Peschon, Sten Eirik W. Jacobsen
Journal: The Journal of Experimental Medicine (2003)

Extensive studies of mice deficient in one or several cytokine receptors have failed to support an indispensable role of cytokines in development of multiple blood cell lineages. Whereas B1 B cells and Igs are sustained at normal levels throughout life of mice deficient in IL-7, IL-7Rα, common cytokine receptor gamma chain, or flt3 ligand (FL), we report here that adult mice double deficient in IL-7Rα and FL completely lack visible LNs, conventional IgM+ B cells, IgA+ plasma cells, and B1 cells, and consequently produce no Igs. All stages of committed B cell progenitors are undetectable in FL−/− × IL-7Rα−/− BM that also lacks expression of the B cell commitment factor Pax5 and its direct target genes. Furthermore, in contrast to IL-7Rα−/− mice, FL−/− × IL-7Rα−/− mice also lack mature B cells and detectable committed B cell progenitors during fetal development. Thus, signaling through the cytokine tyrosine kinase receptor flt3 and IL-7Rα are indispensable for fetal and adult B cell development.
Anterior Colporrhaphy versus Transvaginal Mesh for Pelvic-Organ Prolapse
Authors: Daniel Altman, Tapio Väyrynen, Marie Ellström Engh, Susanne Axelsen, Christian Falconer
Journal: New England Journal of Medicine (2011)

The use of standardized mesh kits for repair of pelvic-organ prolapse has spread rapidly in recent years, but it is unclear whether this approach results in better outcomes than traditional colporrhaphy.
Fetal gene defects precipitate platelet-mediated pregnancy failure in factor V Leiden mothers
Authors: Rashmi Sood, Mark Zogg, Randal J. Westrick, Yi-he Guo, Edward J. Kerschen, Guillermina Girardi, Jane E. Salmon, Shaun R. Coughlin, Hartmut Weiler
Journal: The Journal of Experimental Medicine (2007)

We describe a mouse model of fetal loss in factor V Leiden (FvL) mothers in which fetal loss is triggered when the maternal prothrombotic state coincides with fetal gene defects that reduce activation of the protein C anticoagulant pathway within the placenta. Fetal loss is caused by disruption of placental morphogenesis at the stage of labyrinth layer formation and occurs in the absence of overt placental thrombosis, infarction, or perfusion defects. Platelet depletion or elimination of protease-activated receptor 4 (Par4) from the mother allows normal placentation and prevents fetal loss. These findings establish a cause–effect relationship for the observed epidemiologic association between maternal FvL status and fetal loss and identify fetal gene defects as risk modifiers of pregnancy failure in prothrombotic mothers. Pregnancy failure is mediated by Par4-dependent activation of maternal platelets at the fetomaternal interface and likely involves a pathogenic pathway independent of occlusive thrombosis. Our results further demonstrate that the interaction of two given thrombosis risk factors produces markedly disparate consequences on disease manifestation (i.e., thrombosis or pregnancy loss), depending on the vascular bed in which this interaction occurs.
No clear evidence from countries that have enforced the wearing of helmets
Authors: D L Robinson
Journal: BMJ (2006)

Do enforced bicycle helmet laws improve public health?While many public health specialists believe this argument has been settled in the affirmative, it remains hotly contested in some quarters.We've provided space to Dorothy Robinson to set out her arguments against legislation and asked Brent Hagel and colleagues to respond No clear evidence from countries that have enforced the wearing of helmets D L RobinsonCase-control studies suggest that cyclists who choose to wear helmets have fewer head injuries than non-wearers.Consequently, the BMA recommended that the United Kingdom introduce and enforce bicycle helmet laws. 1 However, regular exercise such as cycling is beneficial to health, and non-helmeted commuter cyclists have lower mortality than non-cyclists. 2Helmet laws would be counterproductive if they discouraged cycling and increased car use.Wearing helmets may also encourage cyclists to take more risks, or motorists to take less care when they encounter cyclists. 3Recent epidemiological research highlighted problems adjusting for confounders in observational studies, causing biased, misleading results. 4Thus the best estimate of the benefits of helmet laws is what actually happens when laws are passed.I reviewed data from all jurisdictions that have introduced legislation and increased use of helmets by at least 40 percentage points within a few months: New Zealand, Nova Scotia (Canada), and the Australian states of Victoria, New South Wales, South Australia, and Western Australia.To avoid confusing reductions in injuries (from safer roads or less cycling) with benefits of helmets, I have focused on percentages of cyclists with head injuries.Head injuries were most commonly classified as admissions to hospital with head wounds, skull or facial fracture, concussion, or other intracranial injury.The data include 10 504 head injuries, and in most cases were available as percentages of all cyclist injuries.Details of data sources and methods are given on bmj.com.
ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia: effects of ?-arginine and B vitamins
Authors: K Sydow
Journal: Cardiovascular Research (2002)

Hyperhomocyst(e)inemia is a risk factor for atherosclerotic vascular disease, and it is associated with endothelial dysfunction. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of NO, possibly secondary to accumulation of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) and increased oxidative stress. We investigated whether oral treatment with B vitamins or L-arginine normalizes endothelium-dependent, flow-dependent vasodilation (FDD) in patients with peripheral arterial occlusive disease (PAOD) and hyperhomocyst(e)inemia.27 patients with PAOD and hyperhomocyst(e)inemia were assigned to oral treatment with combined B vitamins (folate, 10 mg; vitamin B-12, 200 microg; vitamin B-6, 20 mg/day), L-arginine (24 g/day) or placebo, for 8 weeks in a double-blind fashion. FDD was determined by high-resolution ultrasound in the radial artery.Vitamin B supplementation significantly lowered plasma homocyst(e)ine concentration from 15.8+/-1.8 to 8.7+/-1.1 micromol/l (P<0.01). However, B vitamins had no significant effect on FDD (baseline, 7.8+/-0.7%, B vitamins, 8.3+/-0.9%, placebo 8.9+/-0.7%; P=n.s.). In contrast, L-arginine treatment did not affect homocyst(e)ine levels, but significantly improved FDD (10.2+/-0.2%), probably by antagonizing the impact of elevated ADMA concentration (3.8+/-0.3 micromol/l) and reducing the oxidative stress by lowering urinary 8-iso-prostaglandin F(2alpha) (baseline, 76.3+/-7.1 vs. 62.7+/-8.3 pmol/mmol creatinine after 8 weeks).Oral supplementation with combined B vitamins during 8 weeks does not improve endothelium-dependent vasodilation in PAOD patients with hyperhomocyst(e)inemia, whereas L-arginine significantly improved endothelial function in these patients. Thus, accumulation of ADMA and increased oxidative stress may underlie endothelial dysfunction under hyperhomocyst(e)inemic conditions. These findings may have importance for evaluation of homocyst(e)ine-lowering therapy.
Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes.
Authors: C J Schultz, H A Neil, R N Dalton, D B Dunger
Journal: Diabetes Care (2000)

OBJECTIVE: The early detection of a rise in albumin excretion within the normal range could permit early intervention to prevent the development of microalbuminuria (MA) in genetically susceptible subjects with type 1 diabetes. In the Oxford Regional Prospective Study we prospectively examined urine albumin excretion during the first years after diagnosis of childhood type 1 diabetes. RESEARCH DESIGN AND METHODS: Between 1986 and 1995, 511 subjects aged &amp;lt; 16 years were recruited at diagnosis and followed for a median of 6 years (range 1-14). In 78 subjects (designated cases), an annual assessment of the albumin-to-creatinine ratio (ACR) in three morning first-void urine samples detected MA (males: ACR &amp;gt; or =3.5 mg/mmol, females: ACR &amp;gt; or =4.0 mg/mmol in two of three urine samples). In 63 of these subjects and 396 normoalbuminuric diabetic control subjects, rates of change of the ACR were calculated as the slope of the ACR over diabetes duration. RESULTS: The baseline ACR (median [interquartile (IQ) range]), as measured at 1-2.5 years' duration of diabetes, was higher in microalbuminuric subjects than in the normoalbuminuric subjects (1.0 mg/mmol [0.6-2.1], n = 52, vs. 0.8 mg/mmol [0.6-1.2], n = 303; P = 0.02). The rate of increase of the ACR in the years before the onset of MA was higher in the microalbuminuric subjects than in the normoalbuminuric subjects (70% per year [37-149], n = 63, vs. 1% per year [-9 to 13], n = 396; P &amp;lt; 0.001). The mean HbA1c level after the onset of puberty was weakly correlated with the rate of change of the ACR (r = 0.11, P = 0.024, n = 418). CONCLUSIONS: Higher levels of ACR within the first 2 years after diagnosis and a significantly higher rate of increase of the ACR within the first 5 years from diagnosis can be detected in subjects who subsequently develop MA. HbA1c is a determinant of risk for MA, but pubertal factors have a greater effect on rates of progression of urine albumin excretion during adolescence in this cohort.
Sildenafil Prevents Change in RhoA Expression Induced by Chronic Hypoxia in Rat Pulmonary Artery
Authors: Vincent Sauzeau, Malvyne Rolli-Derkinderen, Stéphanie Lehoux, Gervaise Loirand, Pierre Pacaud
Journal: Circulation Research (2003)

Exposure to chronic hypoxia (CH) induces a sustained pulmonary hypertension associated with structural and functional changes in the pulmonary arterial bed, including alterations of contractile properties. The small G-protein RhoA and its effector Rho kinase play a major role in the sustained rise in tension induced by vasoconstrictors. The aim of this study was to analyze the effect of CH on the RhoA/Rho kinase signaling pathway in the rat pulmonary artery. Maximal contraction of pulmonary artery rings to endothelin-1, noradrenaline, and the thromboxane A2 analog U46619 was markedly decreased in rats exposed to CH (10% O2, 2 weeks). This CH-induced decrease response to agonists was attributable to the abolition of RhoA-mediated Ca2+ sensitization of the contraction. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis revealed a decrease in RhoA mRNA (79.4+/-6.0%, n=4) and RhoA (81.1+/-8.0%, n=4) expression in the main pulmonary artery from CH rats, whereas RhoA expression was not modified in arterial smooth muscle cells and arteries exposed to hypoxia and high intraluminal pressure, respectively. Treatment of rats with sildenafil (25 mg/kg per day) throughout 2 weeks of exposure to CH prevented CH-induced downregulation of RhoA, reduction of contraction, and pulmonary artery remodeling. These findings indicate that CH-induced downregulation of RhoA expression, leading to the abolition of RhoA/Rho kinase-mediated Ca2+ sensitization of contraction, is responsible for the decreased responses to contracting agonists in the pulmonary artery of CH rats. These alterations are prevented by sildenafil, indicating a major role of the NO/cyclic GMP pathway in CH-induced altered RhoA signaling in the pulmonary artery.
If Called by the Insurance Company, Call in the Patient on the Call
Authors: C. Keith Whittaker
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Health insurance companies and their managers or administrators in our area have taken up the practice of calling the attending physician, allegedly to get information on why a patient whom they insure needs to be in the hospital, but in actuality, to pressure the physician for early discharge. I believe that these conversations compromise my primary function as a patient advocate. I have recently started to refuse to speak with any representative of an insurance company unless the patient or a patient surrogate (a family member, for example) is simultaneously on the line. This has served the valuable purpose of incorporating the patient into such decisions; it has also made the insurance companies deal with those they insure, and it has been enlightening to me and to the patients. Insurance companies either refuse to talk under these circumstances (to their own insured!) or adopt a hard line
Re-Reading On Death &amp; Dying: What Elisabeth Kubler-Ross Can Teach Clinical Bioethics
Authors: Mark G. Kuczewski
Journal: The American Journal of Bioethics (2004)

The best book in bioethics that I read this year was published in 1969, Elisabeth Kubler-Ross's On Death and Dying. By coincidence, a couple of days before this renowned author's death, I picked up...
EVIDENCE FOR HUMAN INFECTION WITH AN HTLV III/LAV-LIKE VIRUS IN CENTRAL AFRICA, 1959
Authors: A.J. Nahmias, J. Weiss, X. Yao, F. Lee, R. Kodsi, M. Schanfield, T. Matthews, D. Bolognesi, D. Durack, A. Motulsky, P. Kanki, M. Essex
Journal: The Lancet (1986)
OHIO STRAINS OF A VIRUS PATHOGENIC FOR INFANT MICE (COXSACKIE GROUP). SIMULTANEOUS OCCURRENCE WITH POLIOMYELITIS VIRUS IN PATIENTS WITH "SUMMER GRIPPE"
Authors: Joseph L. Melnick, Nada Ledinko, Albert S. Kaplan, Lisbeth M. Kraft
Journal: The Journal of Experimental Medicine (1950)

Further evidence for the widespread occurrence of Coxsackie or C virus is presented in this paper. This virus is characterized by paralysis and myositis produced in infant mice. An epidemic of mild illnesses diagnosed as "non-paralytic poliomyelitis" and as "summer grippe" occurred during the summer of 1947 in Akron and Cincinnati, Ohio. From the pooled feces of such patients both poliomyelitis virus and C virus were obtained. From the samples of single patients, 3 immunologically related strains of C virus were isolated. One patient from whom virus was isolated had an illness which was diagnosed as non-paralytic poliomyelitis (with pleocytosis). Although poliomyelitis virus could not be isolated from this patient, previous tests (5) from similar non-paralytic patients in the same area revealed that 9 of 23 were infected with poliomyelitis virus. C virus could not be recovered from the stools of 3 of these poliomyelitis virus-infected patients. Four patients with an illness diagnosed as "summer grippe" were tested. Two harbored poliomyelitis virus of low virulence (4) as well as C virus, and two harbored poliomyelitis virus without any evidence of infection with C virus, either by virus isolation or by serological tests. The patients from whom C virus was isolated developed complement-fixing antibodies 4 weeks after onset. Neutralizing antibodies appeared within the first 5 days of disease (before complement-fixing antibodies) and increased in titer during the next 3 to 4 weeks. The patients from whom C virus could not be recovered failed to develop either neutralizing or complement-fixing antibodies. Other patients in the area were infected with C virus as indicated by their serological response to the agent.
Dual Promoter–Controlled Oncolytic Adenovirus CG5757 Has Strong Tumor Selectivity and Significant Antitumor Efficacy in Preclinical Models
Authors: Yuanhao Li, Neeraja Idamakanti, Trini Arroyo, Steve Thorne, Tony Reid, Scott Nichols, Melinda VanRoey, Gail Colbern, Natalie Nguyen, Orlena Tam, Peter Working, De-Chao Yu
Journal: Clinical Cancer Research (2005)

Transcriptionally controlled oncolytic adenovirus CG5757 is engineered with two tumor-specific promoters from E2F-1 and human telomerase reverse transcriptase genes. This virus has broad anticancer spectrum and higher specificity. The objective of the current study is to show its antitumor selectivity and therapeutic potential.The antitumor specificity of E2F-1 and human telomerase reverse transcriptase promoters was evaluated in a panel of tumor and normal cells. Under the control of these promoters, the tumor-selective expression of E1a and E1b genes was evaluated. Further in vitro antitumor specificity and potency of this virus were characterized by viral replication and cytotoxicity assays followed by a newly developed ex vivo tumor culture assay. Subsequently, in vivo antitumor efficacy and toxicology studies were carried out to assess the therapeutic potential of this oncolytic agent.In a broad panel of cells, E2F-1 and human telomerase reverse transcriptase promoters were activated in a tumor-selective manner. Under the control of these promoters, expression of E1a and E1b genes appears only in tumor cells. This specificity is extended to viral replication and hence the cytotoxicity in a broad range of cancer cells. Furthermore, CG5757 only replicates in cancer tissues but not in normal tissues that are derived from clinical biopsies. The safety profile was further confirmed in in vivo toxicology studies, and strong efficacy was documented in several tumor xenograft models after CG5757 was given via different routes and regimens.CG5757 has strong antitumor selectivity and potency. It has low toxicity and has great potential as a therapeutic agent for different types of cancers.
Serum Retinol Levels and the Risk of Fracture
Authors: Karl Michaëlsson, Hans Lithell, Bengt Vessby, Håkan Melhus
Journal: New England Journal of Medicine (2003)

Although studies in animals and epidemiologic studies have indicated that a high vitamin A intake is associated with increased bone fragility, no biologic marker of vitamin A status has thus far been used to assess the risk of fractures in humans.