tbuckley/cabot-search huggingface dataset:
Light at Night, Shiftwork, and Breast Cancer Risk
Authors: J. Hansen
Journal: JNCI Journal of the National Cancer Institute (2001)

Breast cancer is the most commonly diagnosed female noncutaneous cancer in the United States and in Europe. The etiology of breast cancer is primarily unknown, with an estimated one quarter of all breast cancers possibly due to heritable factors (1) and only a minor proportion possibly due to already established environmental risk factors, such as early age at menarche, older age at first pregnancy, and delayed menopause (2). Because the incidence of breast cancer in many countries is increasing, for unclear reasons, it is not surprising that society is demanding explanations for the increased incidence of the disease and that researchers are searching for new causes. One avenue of research has been the so-called “man-made endocrine disrupting chemicals,” such as 2-(chlorphenyl)-2-(4-chlorphenyl)-1,1,1-trichlorethan (DDT), polychlorinated biphenyls, or nonyl phenols (3). So far, however, the results from this research have been sparse in expanding our knowledge about risk factors for breast cancer. In this issue of the Journal, two independent epidemiologic studies by Davis et al. (4) and Schernhammer et al. (5) have provided evidence about another potential risk factor, light at night. These studies (4,5) support a hypothesis published about 10 years ago by the former group that light at night may be a potential risk factor of breast cancer (6,7). The scientific rationale behind this intriguing hypothesis is that exposure to visible light, including artificial light, suppresses the normal nocturnal production of melatonin by the pineal gland (6). Melatonin is a mammalian hormone involved in circadian rhythms and sleep and potentially in restraining tumor growth (8). The synthesis and release of melatonin occur in a dose–response-like manner that is stimulated by darkness and inhibited by light through photic information from the retina. Peak melatonin levels normally occur during sleep in the middle of the night (8). Several experimental studies have provided evidence of an association between melatonin levels and risk of cancer. For example, evidence from rodent studies found that pinealectomy increased tumor growth (9), that administration of melatonin inhibited the promotion of chemically induced mammary tumors (9,10), and that constant light exposure had a growth-promoting effect on chemically induced tumors (11). Evidence in humans is less direct, although impaired pineal secretion of melatonin is associated with an increased release of estrogen by the ovaries (7,8), and low serum melatonin concentrations have been reported in women with estrogen receptorpositive breast cancer (8). In vitro, physiologic concentrations of melatonin inhibited the growth of human breast cancer cells
Proceedings: Metabolic studies of thiopurinol in man and pig.
Authors: R Grahame, H A Simmonds, A Cadenhead, B M Dean
Journal: Annals of the Rheumatic Diseases (1974)

Heberden Society 409 vertebral joints is readily found.I have a macerated specimen of a rhematoid spine in which every costo- vertebral joint shows naked eye erosive change.Indeed the costovertebral joints, that is to say the facets on the
The iron triangle of Japan's health care
Authors: James Kondo
Journal: BMJ (2005)

The Japan Medical Association is losing its grip on healthcare policy 

M edical associations around the world influence healthcare policies in their respective countries. Policy makers turn to professionals for guidance on complex issues, so it is only natural that medical associations exert their influence through their knowledge. However, expertise alone cannot explain the influence of the Japan Medical Association on healthcare policy in post war Japan. The association's post war foundation was built during the 25 year presidency of Taro Takemi from 1957 to 1982. Takemi's uncle-in-law, Shigeru Yoshida, was Japan's first post war prime minister. This connection gave Takemi and the association unrivalled access to Yoshida and his successors in the ruling party. Through its influence on the ruling party, the association forced Japan's Ministry of Health, Labour, and Welfare to take heed and dictated much of healthcare policy.

Building on the legacy that Takemi created, currently the association boasts a membership of 159 000, a budget of 16bn yen (£83.4m; $155m; €119m), and an annual political donation fund of …
Platelet-activating factor-mediated transmembrane signaling in human B lymphocytes is regulated through a pertussis- and cholera toxin-sensitive pathway.
Authors: B D Mazer, H Sawami, A Tordai, E W Gelfand
Journal: Journal of Clinical Investigation (1992)

Platelet-activating factor (PAF) stimulates human B cells, resulting in elevation of intracellular calcium and the release of inositol phosphates. This signaling pathway is inhibited in the presence of pertussis (PT) or cholera toxin (CT). Preincubation of human B cells with either toxin, but not their inactive subunits, for 3 h blocked these PAF-induced responses in two B-lymphoblastoid cell lines. This effect was time dependent, with some inhibition noted at 30 min, but only after preincubation for 2-3 h was maximum inhibition achieved. This inhibitory activity was also dose dependent. The toxins blocked both PAF-induced transmembrane uptake of Ca2+ as well as release of Ca2+ from internal stores, and were selective in that activation events after cross-linking of surface IgM were not affected. Further, the toxins did not appear to act through elevation of intracellular levels of cAMP. These data, coupled with previous observations on the absence of heterologous desensitization between PAF and sIgM receptors, may delineate distinct signaling pathways in human B cells. This may reflect different roles for GTP-binding proteins in the activation of human B cells.
Bone Morphogenetic Proteins Regulate the Developmental Program of Human Hematopoietic Stem Cells
Authors: Mickie Bhatia, Dominique Bonnet, Dongmei Wu, Barbara Murdoch, Jeff Wrana, Lisa Gallacher, John E. Dick
Journal: The Journal of Experimental Medicine (1999)

The identification of molecules that regulate human hematopoietic stem cells has focused mainly on cytokines, of which very few are known to act directly on stem cells. Recent studies in lower organisms and the mouse have suggested that bone morphogenetic proteins (BMPs) may play a critical role in the specification of hematopoietic tissue from the mesodermal germ layer. Here we report that BMPs regulate the proliferation and differentiation of highly purified primitive human hematopoietic cells from adult and neonatal sources. Populations of rare CD34+CD38−Lin− stem cells were isolated from human hematopoietic tissue and were found to express the BMP type I receptors activin-like kinase (ALK)-3 and ALK-6, and their downstream transducers SMAD-1, -4, and -5. Treatment of isolated stem cell populations with soluble BMP-2, -4, and -7 induced dose-dependent changes in proliferation, clonogenicity, cell surface phenotype, and multilineage repopulation capacity after transplantation in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Similar to transforming growth factor β, treatment of purified cells with BMP-2 or -7 at high concentrations inhibited proliferation yet maintained the primitive CD34+CD38− phenotype and repopulation capacity. In contrast, low concentrations of BMP-4 induced proliferation and differentiation of CD34+ CD38−Lin− cells, whereas at higher concentrations BMP-4 extended the length of time that repopulation capacity could be maintained in ex vivo culture, indicating a direct effect on stem cell survival. The discovery that BMPs are capable of regulating repopulating cells provides a new pathway for controlling human stem cell development and a powerful model system for studying the biological mechanism of BMP action using primary human cells.
CT colonoscopy in 2007: the next standard for colorectal cancer screening in average-risk subjects?
Authors: D. Heresbach, T. Ponchon
Journal: Endoscopy (2007)

Over a decade has passed since computed tomographic colonography (CTC) was first described as a potential tool for the detection of colonic polyps. Today CTC is highly specific, but the range of reported sensitivities is wide. Patient or scanner characteristics do not fully account for this variability, but collimation, the number of CT detectors, the mode of imaging, and operator expertise do explain some of the discrepancies. In the present issue of Endoscopy, Kim et al. [1] describe the meticulous technique they used at the University of Wisconsin and explain how they have organized an active CTC-based screening program for colorectal carcinoma (CRC). However, the role of CTC in CRC screening is still debatable, and their interesting paper raises three major issues which ought to be discussed:
p53 Protein Transduction Therapy: Successful Targeting and Inhibition of the Growth of the Bladder Cancer Cells
Authors: Miyabi Inoue, Kazuhito Tomizawa, Masayuki Matsushita, Yun-Fei Lu, Teruhiko Yokoyama, Hiroyuki Yanai, Atsushi Takashima, Hiromi Kumon, Hideki Matsui
Journal: European Urology (2005)
Effect of the Pericardium on Left Ventricular Volume and Function in Acute Hypervolaemia
Authors: S. H. Bartle, H. J. Hermann, J. W. Cavo, R. A. Moore, J. M. Costenbader
Journal: Cardiovascular Research (1968)

The effect of acute volume overload was studied in 20 dogs, nine of which had undergone pericardiectomy. End-diastolic and end-systolic left ventricular volumes, as determined by biplane angiocardiography, were significantly higher, and the ejected fraction relatively lower in the pericardiectomized group. It is concluded that the pericardium prevents excessive left ventricular dilatation and impairment of the ventricular function during acute hypervolaemia.
STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1933)

By a method combining filtration and cultivation an unidentified Gram-negative bacillus was isolated from the nasal exudate of fowl experimentally infected with an uncomplicated coryza. Isolation was accomplished by cultivation on sealed blood agar plates after unsuccessful attempts to produce colonies on open plates. Injection of the organism into the palatine cleft of normal birds was regularly followed by an inflammation of the nasal mucosa and a discharge from the nares. A para-influenza bacillus which was also recovered from the nasal tract of affected fowl was innocuous. Certain cultural characters of the bacillus, bearing on its classification, are discussed.
Advantages and disadvantages of neonatal circumcision
Authors: I. R. Berman
Journal: JAMA (1997)

To the Editor.  —Dr Laumann and colleagues 1 conclude that circumcision provides no preventive medical benefit, thus reviving an ongoing controversy. While issues related to the risk of childhood urinary tract infection with and without circumcision may be debatable, the authors have been blinded to the medical benefits of circumcision for adults. Indeed, only 1 week following the report by Laumann et al, Royce et al 2 reported that male circumcision consistently shows a protective effect against HIV infection, with an 8-fold increased rate of HIV disease among uncircumcised men. 2 Royce et al further report a greater incidence of HIV in sexual partners of uncircumcised men and speculate that the abundance of Langerhans cells in the foreskin may be a contributing factor and that the presence of a foreskin actually may increase infectiousness.  Periodic arguments against circumcision have been supported by a variety of evidence, much of which has been directed toward
501. RheoSwitch® Therapeutic System-Inducible Recombinant AAV Vectors for Tightly Regulated Transgene Expression
Authors: Dawn Karzenowski, ZhijianJ. Chen, DavidW. Potter, Malla Padidam
Journal: Molecular Therapy (2006)

Recent advances in recombinant AAV (rAAV) vector technology have made rAAV a vector of choice for many gene therapy applications. rAAV vectors for delivery of the RheoSwitch® Therapeutic System (RTS) are ideal systems for regulatory control of long-term therapeutic gene expression in vivo. RTS inducible gene expression technology allows the precise timing and dose of the therapeutic protein to be controlled through the systemic administration of a highly specific, pharmacologically inert Activator Drug. The controlled expression of the gene of interest is activated by the RheoSwitch® receptor (a heterodimer of an engineered ecdysone receptor ligand binding domain fused to a GAL4 DNA binding domain (GAL4:EcR) and an RXR protein fused to a VP16 activation domain (VP16:RXR)) only in the presence of Activator Drug. In the present study, we have optimized rAAV-based vectors by using different promoters for the expression of RheoSwitch® receptor and by cloning the inducible transgene and the RheoSwitch® receptor-expressing cassettes in different orientations. We then used a highly active, modified CMV promoter for the expression of RheoSwitch® receptor and cloned the receptor cassette and inducible Gaussia luciferase (GLuc) or GFP cassette in a single rAAV. To evaluate the regulation of GLuc or GFP transgene expression, HEK293 and mouse neural stem cells (NSCs) were transduced with packaged virus. Addition of Activator Drug to transduced HEK293 and NSCs in culture induced transgene expression in a dose dependent manner. For in vivo evaluation, the packaged virus was injected into the quadriceps of mice and subsequently induced with Activator Drug. Both the inducible GLuc and GFP vectors demonstrated little or no basal activity and inducible expression. To reduce the size of the construct further, we tested a format in which a p53 activation domain was fused to the GAL4:EcR domain. This gene was cloned with an inducible secretable alkaline phosphatase (SEAP) in a single rAAV vector. Activator Drug-dependent induction and low basal activity were also observed for this format in vitro and in vivo. Regulatable rAAV vectors based on these designs are ideal for therapeutic gene delivery.
Imaging thrombus with radiolabelled monoclonal antibody to platelets.
Authors: A M Peters, J P Lavender, S G Needham, I Loutfi, D Snook, A A Epenetos, P Lumley, R J Keery, N Hogg
Journal: BMJ (1986)

Indium-111-hydroxyquinoline labelled platelets, though useful in the detection of thrombus, have not gained widespread use owing to the time and technical skill required for their preparation. A study was therefore conducted evaluating a new method of imaging thrombus with platelets radiolabelled with a 111In labelled monoclonal antibody, P256, directed to the platelet surface glycoprotein complex IIb/IIIa. When the number of receptors occupied by P256 was less than 3% of the total available on the platelet surface platelet function, as assessed by platelet aggregometry, was undisturbed. P256 was radiolabelled with 111In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo--that is, by direct intravenous injection of P256--in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The 111In kinetics recorded after intravenous P256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P256, three had documented thrombus, two of whom gave positive results on P256 platelet scintigraphy. The third subject had chronic deep venous thrombosis and was scintigraphically negative. Imaging thrombus using a radiolabelled monoclonal antibody directed to platelets appears to offer great potential as a simple, non-invasive approach to the diagnosis of thrombosis.
Tc-99m MDP Uptake in Retroperitoneal Fibrosis
Authors: Weifang Zhang, Yanyan Zhang
Journal: Clinical Nuclear Medicine (2009)

A 60-year-old man with a history of surgical resection of leiomyosarcoma of the right kidney had a bone scan to evaluate possible metastatic osseous disease. The bone scan showed significantly increased Tc-99m MDP activity in the right abdomen, corresponding to a heterogeneous mass in the right retroperitoneal region on the subsequent abdominal CT scan. These findings were initially interpreted as recurrent malignancy. However, the surgical pathology examination demonstrated that the lesion was retroperitoneal fibrosis, which was not previously known to have increased MDP uptake.
Surveillance Colonoscopy and Biopsy in Patients with Ureterosigmoidostomy
Authors: N.O. Berg, P. Fredlund, W. Månsson, S.-Å. Olsson
Journal: Endoscopy (1987)

Colonoscopy with biopsy was included in the surveillance of 19 patients with ureterosigmoidostomy, because of the high incidence of colonic carcinoma reported in such cases. The patients were examined 1-6 times, at intervals of 1-2 years, 4-36 years after the urinary diversion. Random biopsies from the distal colon and rectum showed only discrete changes, and no dysplasia. Polyps with dysplastic changes were found close to ureteral anastomoses in three patients. For routine check-up of the rectosigmoid region and the ureteral implantation sites, examination with a flexible sigmoidoscope seems to be adequate and preferable, giving easy access to the risk zone for the development of cancer. Caution should be exercised, however, when performing biopsy close to the ureteral orifices.
Goodbye to Fibrocystic Disease
Authors: Robert V.P. Hutter
Journal: New England Journal of Medicine (1985)

IT is time to empty the "fibrocystic disease" waste-basket and thereby mitigate the anxiety of a large number of women who no longer need to be concerned about a high risk for breast cancer. Love et al. have asked, "Is it reasonable to define as a disease any process that occurs clinically in 50 per cent and histologically in 90 per cent of women?"1 During the past year there were about 115,000 new cases of breast cancer and 37,000 deaths from the disease in the United States, where it occurs in 1 of every 11 women, and each of the . . .
Capsule Endoscopy in Patients with Obscure Gastrointestinal Bleeding
Authors: M. Delvaux, I. Fassler, G. Gay
Journal: Endoscopy (2005)

The diagnosis of the source of bleeding in patients with obscure digestive bleeding has considerably improved, with a significant influence on the outcome for patients, since the introduction of capsule endoscopy - as shown by numerous studies reporting a higher diagnostic yield with capsule endoscopy in comparison with push enteroscopy and by our recent study [1], on which Dalla Valle et al. have commented [2]. The issue of lesions missed during previous endoscopic examinations was been identified even before the introduction of capsule endoscopy, with several studies on push enteroscopy showing that some 25 % of the lesions detected by push enteroscopy were within the range of a routine esophagogastroduodenoscopy [3] [4]. In the lower gastrointestinal tract, retrograde ileoscopy had a low diagnostic yield and was abandoned by most clinical teams, who limited the exploration to the terminal ileum during colonoscopy [5].
The Quandaries of Mass Immunization
Authors: F.J. Ingelfinger
Journal: New England Journal of Medicine (1976)

Not until next spring, and perhaps never, will a reasonably valid assessment of the USA swine-influenza immunization program be possible. In the meantime, the program stumbles along with estimates in early September that the amount of vaccine ready for delivery by October 1 will be only one quarter of that expected.1 At the same time, the number to be vaccinated before the flu season arrives is being reduced by recommendations that would eliminate most of the population under 25 years of age, or would concentrate on giving available supplies to high-risk groups.2 The only safe prediction in this shifting scene . . .
Immune Mechanisms Are Major Players in Cancer
Authors: Karl Erik Hellstrom, Ingegerd Hellstrom
Journal: Clinical Cancer Research (2015)

Vaccination with sipuleucel-T produced IgG antibodies to secondary prostatic carcinoma antigens and prolonged survival in some patients, and assaying for antibodies may provide prognostic information and identify new vaccine targets. Additional approaches to improve T-cell responses are needed to improve the clinical efficacy. See related article by GuhaThakurta et al., p. 3619.
A focus on farming health in Iowa.
Authors: J Barrett
Journal: Environmental Health Perspectives (1999)

A Focus on Farming Health in IowaTo many people, the words "rural life" conjure images of pastoral landscapes l and farmers reaping the earth's bounty.The reality is, however, that agrarian systems pre-envirc sent their own distinct hazards and rural com- n munities face specific sd environmental health risks.The Environmental res Health Sciences Research Center (EHSRC) at the University of Iowa in Iowa City is the only NIEHS center to focus primarily on rural environ- mental exposures and the effects that such exposures have on human health.Most of Iowa is rural; of the 99 coun- ties in Iowa, 88 are rural, and agriculture remains the primary industry.Thus, says James Merchant, a professor of preventive and internal medicine and the center director, it makes sense that this particular center emphasizes rural environmental health.Rural and agricultural exposures are viewed from several aspects, as reflect- ed in the center's diverse research cores: cancer, pulmonary biology, occupational health, environmental assessment and control, and genetics and reproductive biology.The center also supports an administrative core and a community out- reach and education core.
Left Ventricular Thrombus Detection by ECG Synchronized Cineangiography
Authors: GARY J. NOVETSKY, LEONARD BERLIN, DAVID A. TURNER, AVRUM J. EPSTEIN
Journal: Clinical Nuclear Medicine (1983)

The detection of a left ventricular mural thrombus, a potentially fatal complication of various heart diseases, is often missed by current radiographic techniques. The findings on ECG synchronized radionuclide cineangiography in a patient with a large thrombus in the left ventricular cavity, confirmed by echocardiography and angiography are reported. This suggests a role for radionuclide cineangiography in the detection of left ventricular mural thrombus.