tbuckley/cabot-search huggingface dataset:
Cre/loxP-mediated CTLA4IgG gene transfer induces clinically relevant immunosuppression via on–off gene recombination in vivo
Authors: A IZAWA, K SANO, M TAKEHARA, M INOBE, J SUZUKI, H IMAMURA, M TAKAHASHI, U IKEDA, M ISOBE, T UEDE
Journal: Cardiovascular Research (2005)

Transfer of the CTLA4IgG gene induces long-term and high levels of CTLA4IgG expression, which can result in generalized immunosuppression. In this study, we utilized Cre/loxP-mediated on-off switch recombination to eliminate transgene expression of CTLA4IgG following acceptance of murine cardiac allografts.Fully MHC-mismatched hearts from BALB/c donor mice were transplanted into C3H/He recipient mice. Adenovirus-containing CTLA4IgG flanked between two loxP sites was administered via a recipient tail vein immediately after transplantation. Cre-recombinase gene was subsequently transferred at day 30 posttransplantation.Long-term allograft survival was observed in recipients that received the CTLA4IgG gene. Cre-mediated recombination reduced CTLA4IgG gene expression without any adverse effect on the graft survival. Secondary skin grafts of donor type and of third party were promptly rejected in the recipients that accepted cardiac allografts. In addition, the B cell response against ovalbumin was suppressed during high levels of serum CTLA4IgG, but recovered after Cre-mediated inactivation of CTLA4IgG gene.CTLA4IgG gene transfer promoted long-term survival of murine cardiac allografts; however, this was not sufficient to induce tolerance. Cre/loxP-mediated on-off switch recombination was useful to inactivate the CTLA4IgG gene so that recipients' immune responses against neoantigens were restored without an influence on the allograft survival. This system may open novel strategies to orchestrate clinically relevant immunosuppression.
Occupational cancer kills more than 200 000 people a year
Authors: Kaushal Raj Pandey
Journal: BMJ (2007)

More than 200 000 people, most of them in the developed world, die each year from a workplace related cancer, the World Health Organization has said in a press release.

A major rise in the incidence of occupational cancer can be expected in developing countries in the coming decades as work processes involving the use of carcinogens shift to countries with less stringent enforcement of occupational health standards, WHO warns. These processes involve substances such as chrysotile asbestos and pesticides and those used in production of tyres and …
Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts.
Authors: H Nagano, R N Mitchell, M K Taylor, S Hasegawa, N L Tilney, P Libby
Journal: Journal of Clinical Investigation (1997)

We have hypothesized that T cell cytokines participate in the pathogenesis of graft arterial disease (GAD). This study tested the consequences of IFN-gamma deficiency on arterial and parenchymal pathology in murine cardiac allografts. Hearts from C-H-2(bm12)KhEg (bm12, H-2(bm12)) were transplanted into C57/B6 (B6, H-2(b)), wild-type, or B6 IFN-gamma-deficient (GKO) recipients after immunosuppression by treatment with anti-CD4 and anti-CD8 mAbs. In wild-type recipients, myocardial rejection peaked at 4 wk, (grade 2. 1+/-0.3 out of 4, mean+/-SEM, n = 9), and by 8-12 wk evolved coronary arteriopathy. At 12 wk, the GAD score was 1.4+/-0.3, and the parenchymal rejection grade was 1.2+/-0.3 (n = 8). In GKO recipients of bm12 allografts, myocardial rejection persisted at 12 wk (grade 2.5+/-0.3, n = 6), but no GAD developed (score: 0.0+/-0.0, n = 6, P < 0.01 vs. wild-type). Mice treated with anti-IFN-gamma mAbs showed similar results. Isografts generally showed no arterial changes. In wild-type recipients, arterial and parenchymal cells showed increased MHC class II molecules, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 compared to normal or isografted hearts. The allografts in GKO recipients showed attenuated expression of these molecules (n = 6). Thus, development of GAD, but not parenchymal rejection, requires IFN-gamma. Reduced expression of MHC antigens and leukocyte adhesion molecules may contribute to the lack of coronary arteriopathy in hearts allografted into GKO mice.
341 PERFORMANCE OF THE FIBROSCAN XL PROBE FOR LIVER STIFFNESS MEASUREMENT IN OBESE PATIENTS: A MULTICENTER VALIDATION STUDY
Authors: R.P. Myers, G. Pomier-Layrargues, A. Duarte-Rojo, D.K. Wong, M.D. Beaton, M.A. Levstik, R. Kirsch, A. Pollett, M. Elkashab
Journal: Journal of Hepatology (2011)
Enhanced Thrombolytic and Antithrombotic Potency of a Fibrin-Targeted Plasminogen Activator in Baboons
Authors: Marschall S. Runge, Laurence A. Harker, Christoph Bode, Johannes Ruef, Andrew B. Kelly, Ulla M. Marzec, Elaine Allen, Rafael Caban, Shyh-Yu Shaw, Edgar Haber, Stephen R. Hanson
Journal: Circulation (1996)

Thrombolytic therapy reduces mortality in patients with acute myocardial infarction, but significant limitations exist with the use of currently available agents. In the present report, we describe the thrombolytic and antithrombotic potencies of a hybrid recombinant plasminogen activator consisting of an antifibrin antibody 59D8 (AFA) and low-molecular-weight single-chain urokinase-type plasminogen activator (scuPA).A thrombolysis model in which thrombi are preformed in vivo in juvenile baboons was developed to compare the potencies of AFA-scuPA, recombinant tissue plasminogen activator (rTPA), and recombinant scuPA (rscuPA) in lysing nonocclusive 111In-labeled platelet-rich arterial-type thrombi and 125I-labeled fibrin-rich venous-type thrombi. Systemic infusion of 1.89 nmol/kg AFA-scuPA produced thrombolysis that was comparable to that obtained with much higher doses of TPA (14.2 nmol/kg) and rscuPA (28.5 nmol/kg). When steady-state plasma concentrations are normalized, AFA-scuPA lyses thrombi sixfold more rapidly than scuPA and TPA (P < .001) and reduces the rate of formation more than comparable doses of rscuPA (P < .0001). At equivalent thrombolytic doses, AFA-scuPA produced fewer antihemostatic effects than either rTPA or rscuPA. Template bleeding time measurements were shorter (3.5 +/- 0.12 minutes for AFA-scuPA versus 5.3 +/- 0.36 and 5.2 +/- 0.04 minutes for rTPA and rscuPA, respectively; P < .05), alpha 2-antiplasmin consumption was less (P < .05), and D-dimer generation was lower (P < .05).We conclude that antibody targeting of scuPA to fibrin increases thrombolytic and antithrombotic potencies with less impairment of hemostasis compared with rTPA and rscuPA.
Human T-Lymphotropic Virus (HTLV I-II) Infection among Patients in an Inner-City Emergency Department
Authors: Gabor D. Kelen, Thomas A. DiGiovanna, Lisa Lofy, Edward Junkins, Allen Stein, Keith T. Sivertson, Michael Dale Lairmore, Thomas C. Quinn
Journal: Annals of Internal Medicine (1990)

Objective: To determine the seroprevalence and epidemiologic features of human T-lymphotropic virus (HTLV I-II) among an emergency department patient population with a high rate of human immunodeficiency virus (HIV-I) infection. Design: Prospective survey using identity-unlinked consecutive sampling during a 6-week period in 1988. Setting: Inner-city teaching hospital. Patients: Sequential sample of 2544 adult patients with sufficient excess sera for analysis. Measurements and Main Results: Twenty-eight (1.1%) (95% CI, 0.7% to 1.5%) serum samples were seropositive for HTLV I-II whereas 152 (6.0%) (CI, 5.1% to 6.9%) were seropositive for HIV-I. The age distribution of HTLV I-II was similar to the study population while HIV-I was concentrated among younger (25 to 44 years) age groups (P < 0.05). Only 16 (57.1%) HTLV I-II infected patients had identified risk factors; 11 were intravenous drug users, 4 received transfusions, and 1 had heterosexual exposure to a high-risk partner. None of 39 identified homosexual men had HTLV I-II antibodies although 29 (74.3%) were HIV-I seropositive. Conclusion: HTLV I-II infection may be more prevalent among certain segments of the U.S. population than previously realized and appears to have a different demographic distribution than HIV-I infection. Although HTLV I-II may represent a nosocomial risk to health care providers, the risk of occupational transmission is probably less than for hepatitis B virus and even HIV-I. Adherence to universal precautions should minimize the risk.
Promoter of vitamins for AIDS calls off lawsuits
Authors: Pat Sidley
Journal: BMJ (2006)

The controversial vitamin manufacturer Mathias Rath has dropped legal action against respected scientist Hoosen Coovadia; several journalists in South Africa; and Eric Goemaere, the local head of humanitarian non-governmental organisation Medecins Sans Frontieres. Mr Rath has been accused of trying to persuade people with HIV/AIDS to use his vitamins rather than anti-retroviral treatment.

But Mr Rath has not dropped his legal action against former cabinet minister Kadar Asmal, a respected academic in exile in Ireland and a leading light in South Africa's ruling party, the African National Congress. Dr Rath's legal action was based on his view that the accusations made …
CLINICAL SEQUENTIAL TRIALS TN DERMATOLOGY
Authors: J. A. MILNE
Journal: British Journal of Dermatology (1970)

Journal Article CLINICAL SEQUENTIAL TRIALS TN DERMATOLOGY Get access J. A. MILNE J. A. MILNE Department of Dermatology, University of Glasgow, Scotland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue s6, 1 June 1970, Page 99, https://doi.org/10.1111/j.1365-2133.1970.tb08013.x Published: 01 June 1970
Early Identification of Type 2 Diabetes
Authors: K.M. Venkat Narayan, Juliana Chan, Viswanathan Mohan
Journal: Diabetes Care (2010)

More than 60% of the estimated 285 million people with diabetes globally are in low- and middle-income countries (LMICs) (1). Largely driven by the growth of type 2 diabetes, the numbers of people with diabetes worldwide is projected to touch at least 450 million by 2030, with the biggest increase happening in LMICs and substantially driven by populous Asian countries like India and China (1). Recent data indicate an urban diabetes age-standardized prevalence of 11.4% in China (2) and 9.1–13.0% in India in the ongoing Indian Council of Medical Research–India Diabetes (ICMR–INDIAB) study (V.M. Anjana, A. Mohan, personal communication). Furthermore, the prevalence of diabetes may be as high as 8.2% among rural residents in China (2) and may vary from 2.8 to 11.9% in rural India, depending on the level of economic development (ICMR–INDIAB study). Importantly, a high proportion of people with type 2 diabetes (50–70% in China [2,3] and 30–80% in India [ICMR–INDIAB study]) remain undiagnosed and thus untreated. Should there, therefore, be an active policy to identify dysglycemia and diabetes early?

As undiagnosed diabetes is frequently associated with potentially preventable costly diabetes complications and concomitant cardiovascular risk factors (4–6), a policy of early identification through systematic or opportunistic means may have some appeal. Indeed, the merits or otherwise of a screening policy for diabetes have been previously reviewed and assessed (7). The consensus thus far has been that type 2 diabetes meets many of criteria for screening, namely, the burden is large, the natural history is well understood, there is a long latent period, and effective and cost-effective treatments for diabetes are available. However, three challenges still remain: 1 ) a reliable, high-performance, convenient, low-cost screening test that can be universally applied has been lacking; 2 ) direct evidence of the benefits and costs …
Significance of indoor environment for the development of allergic symptoms in children followed up to 18 months of age
Authors: D. Gustafsson, K. Andersson, I. Fagerlund, N.-I. M. Kjellman
Journal: Allergy (1996)

The development of symptoms possibly related to allergy or other forms of hypersensitivity was studied in a group of 638 children on two occasions: when the children were 3 and 18 months of age. Standardized questions were used to collect basic information about the child, technical characteristics of the home, and the mother's perception of the indoor climate. All reported exposure factors were analyzed in relation to the child's symptoms at 18 months of age, by logistic regression techniques. A family history of atopy was associated with a high incidence of most of the investigated symptoms. Attendance at a day nursery before 18 months of age increased the risk of recurrent colds and the need for several courses of treatment with antibiotics. If the mother smoked, the children more often suffered from protracted coughing episodes. If the child has a sibling, the risk of developing a wheeze, repeated colds, and the need for antibiotic treatment increased. No building factors, such as size of the home, heating and ventilation system, type of foundation, dampness, or presence of wall-to-wall carpets, showed a significant correlation to symptoms reported in the children. However, if the mothers reported symptoms that are often connected with "sick buildings", the children more often had eczema, dry skin, or reactions to food. The mothers' complaints about indoor air quality and climate and mucous membrane symptoms were significantly related to the type of building and presence of condensation on the windows in winter, a finding which may indicate that indoor climate factors also have some effect on the health of the children. This study reports the prevalences of symptoms until the age of 18 months. At this age, the allergic manifestations are usually nonspecific, and follow-up examinations to 4-5 years of age are needed before any definite conclusions can be drawn about the development of atopic diseases due to indoor climate factors.
Suicide by Related Kidney Donors following the Recipients’ Death
Authors: Nechama Weizer, Abraham Weizman, Zaki Shapira, Alexander Yussim, Hanan Munitz
Journal: Psychotherapy and Psychosomatics (1989)

Two cases of suicide by related kidney donors following graft rejection and the death of the recipients are reported. It is concluded that psychiatric screening of the donor before transplantation is necessary in order to obtain information about past psychopathology, ambivalence involved in donating the kidney, psychological style, characteristic defenses and behavioral repertoire used to cope with anxiety and disappointed life circumstances. The data are necessary to assess the donor's capability of accepting a possible failure of the transplantation procedure. A psychiatric evaluation after transplantation is indicated following graft rejection and death of the recipient to assess the development of depression and suicidal potential of the related donor.
The Effects of Polyunsaturated Fat vs Monounsaturated Fat on Plasma Lipoproteins: The Power of a Study-Reply
Authors: Darlene M. Dreon
Journal: JAMA (1990)

In Reply.—  On our study of diet and high-density lipoprotein cholesterol subfractions, Dr Passey has focused on the negative low-density lipoprotein (LDL) cholesterol results. We designed our study with β error equal to .20 specifically to detect differences in highdensity lipoprotein cholesterol and cholesterol subfractions. We obtained significant differences for these variables and therefore think that the study groups were of sufficient size to report these positive results appropriately.  While change in LDL cholesterol was not part of our primary hypothesis, clearly LDL cholesterol has a greater SE and greater differences would be needed with this sample size to obtain significance. With 80% power we could detect significance with an LDL cholesterol difference of 0.28 mmol/L, below which are levels we consider clinically insignificant. We consider the nonsignificant change in LDL cholesterol of 0.10 mmol/L to be of little clinical significance.  We faithfully pointed out not only our P value but
Letter to an unknown health minister
Authors: Tony Delamothe
Journal: BMJ (2011)

Legislation, regulation, and taxation are the best ways to change behaviour



Dear Minister

I imagine you in your suite at the Millennium UN Plaza Hotel, pondering how to justify your entourage’s trip to the United Nations summit on non-communicable diseases this week. You already knew that heart disease, lung disease, cancer, and diabetes together kill more than half the people in your country. The summit recognised that prevention must be the cornerstone of global and national responses to non-communicable diseases ( BMJ 2011;343:d6034, doi:10.1136/bmj.d6034). So what have you decided to do about the risk factors targeted by the summit: tobacco use, unhealthy diet, lack of physical activity, and alcohol misuse?

I wasn’t at the summit, but the participants I’ve talked to were disappointed that food and alcohol companies got off so lightly. But don’t despair: so much was published in the run up to the summit that a consensus about future action is emerging.

But firstly I need to get a few apologies out of the way. I’m sorry that some Western countries with antismoking policies to protect their own citizenry lobbied against imposing fiscal penalties on tobacco elsewhere. And that they resisted …
Hypoglossal nerve stimulation affects the pressure-volume behavior of the upper airway.
Authors: W Hida, H Kurosawa, S Okabe, Y Kikuchi, J Midorikawa, Y Chung, T Takishima, K Shirato
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

To determine the effects of electrical hypoglossal nerve and submental stimulation on upper airway collapsibility, we examined the pressure-volume (P-V) relationships during bilateral supramaximal stimulation of the distal cut hypoglossal nerve ends over a range of frequencies from zero to 100 Hz in the sealed upper airway of 10 anesthetized supine dogs. Animals were artificially ventilated with 50% O2 and maintained under relative hyperoxia and hypocapnia during the study to eliminate the ventilatory drive output. Sealed upper airway pressures were obtained during random injections of different volumes of air from zero to 50 ml with and without hypoglossal nerve stimulation, and the upper airway P-V curves were obtained. The characteristics of the P-V curves were as follows: (1) the upper airway compliance defined as the slope of the regression of P-V curves fell from 4.07 +/- 0.33 ml/cm H2O without stimulation to 3.02 +/- 0.30 ml/cm H2O with stimulation at 50 Hz and plateaued at frequencies greater than 50 Hz, and (2) the volume at a given pressure during stimulation was larger than that without stimulation. The effects of submental stimulation on upper airway collapsibility were similar to those of hypoglossal nerve stimulation. These results suggest that the increase of upper airway muscle tone by hypoglossal nerve or submental stimulation stiffens the upper airway and that increases in muscle tone expand the upper airway.
Hizbollah rocket hits hospital
Authors: Judy Siegel-Itzkovich
Journal: BMJ (2006)

The 350 bed Ziv Hospital in the northern Galilee city of Safed was hit by a Hizbollah rocket on 18 July, causing a quarter of its windows to be smashed and wounding eight people, including one doctor. The Israeli health minister, Ya'acov Ben-Yizri, ordered the fortification of all oxygen tanks in northern hospitals, as a direct hit would have disastrous consequences. 

As a result …
Government and industry reach new pricing deal to cut NHS drugs bill
Authors: Andrew Jack
Journal: BMJ (2008)

The government and the drug industry this week reached an outline agreement on a new contract for drug prices in the United Kingdom over the next five years. It is expected that the deal will cut the annual £9bn (€11bn; $18bn) drug bill in the UK’s health services by 5% by 2009.

The announcement follows a year of intense and tough negotiations after the Department of Health said it was unilaterally cancelling the current pharmaceutical price regulation scheme (PPRS) halfway through its planned duration ( BMJ 2007;335:273 doi: 10.1136/bmj.39300.405822.DB).

The PPRS, which normally runs for five years, allows companies to set drug prices freely …
Late referral for maintenance dialysis.
Authors: P J Ratcliffe, R E Phillips, D O Oliver
Journal: BMJ (1984)

A study of patients accepted for maintenance dialysis at the Oxford renal unit in 1981 showed that 23 out of 55 patients were referred late, very shortly before the need for dialysis. This pattern of referral was associated with a higher morbidity at the start of dialysis which may have been preventable. In the late referral group 16 patients (70%) suffered major complications and three (13%) died; by contrast, in the early referral group three patients (9%) suffered complications and one died. Early referral to a renal unit plainly benefits the patient and allows Health Service resources to be used more economically.
Predicting fetal death by measuring oestrogen:creatinine ratios on early morning samples of urine.
Authors: L G Rao
Journal: BMJ (1977)

Total oestrogens were measured, on a creatinine basis, by a fully automated method in 75 000 early morning specimens of urine from 5429 women. Among the 5241 pregnancies in which the oestrogen:creatinine ratio was normal there were 11 fetal deaths (0-21%). But there were 57 fetal deaths (30-3%) among 188 patients with ratios below the fifth centile. When delivery took place before the ratio decrease to below the fifth centile a live baby was born in every one of 59 pregnancies. Apart from its effectiveness in predicting fetal death, the test has a high degree of precision and can be performed swiftly, and cheaply. For these reasons the assessment of fetoplacental function by measuring the urinary:creatinine ratio could become a convenient and inexpensive part of antenatal care that could be extended to every pregnant woman without making many further demands on obstetricians' time.
<i>p</i>-Coumaric acid, a constituent of<i>Sasa quelpaertensis</i>Nakai, inhibits cellular melanogenesis stimulated by -melanocyte stimulating hormone
Authors: S.M. An, S.I. Lee, S.W. Choi, S.-W. Moon, Y.C. Boo
Journal: British Journal of Dermatology (2008)

Recent study has demonstrated that Sasa quelpaertensis (Korean name, Jeju-Joritdae) extracts inhibit cellular melanogenesis implicating potential use in the control of skin pigmentation.The purpose of the present study was to elucidate the active constituents of this plant inhibiting melanogenesis and the associated mechanism.The effect of the plant-derived materials on melanin production and/or tyrosinase expression was examined in murine melanoma B16/F10 cells and neonatal human melanocytes.When tested in melanoma B16/F10 cells treated with the alpha-melanocyte stimulating hormone (alpha-MSH), the aqueous ethanol extract of S. quelpaertensis culm inhibited the cellular melanogenesis more effectively than its leaf extract. A major active compound was isolated from the culm extract by solvent fractionation and column chromatography, and identified to be p-coumaric acid by spectroscopic and chromatographic analyses. The compound (p-coumaric acid) inhibited alpha-MSH-stimulated cellular melanogenesis more effectively than arbutin or other structurally similar compounds including 3-(4-hydroxyphenyl) propionic acid, cinnamic acid and caffeic acid. It also attenuated alpha-MSH-dependent increase of tyrosinase protein. The antimelanogenic effect of p-coumaric acid was also verified in neonatal human melanocytes.The present study identified p-coumaric acid as a main constituent of S. quelpaertensis inhibiting cellular melanogenesis. Because of its structural similarity, p-coumaric acid may interfere with l-tyrosine action in the control of tyrosinase expression in response to alpha-MSH.