tbuckley/cabot-search huggingface dataset:
Correction of Liver Disease Following Transplantation of Normal Rat Hepatocytes into Long–Evans Cinnamon Rats Modeling Wilson's Disease
Authors: Adil N. Irani, Harmeet Malhi, Sanjeev Slehria, Giridhar R. Gorla, Irene Volenberg, Michael L. Schilsky, Sanjeev Gupta
Journal: Molecular Therapy (2001)

To establish the efficacy of cell therapy in Wilson's disease, we used the Long–Evans Cinnamon (LEC) rat model with atp7b gene mutation and copper toxicosis. Several groups of LEC rats were established, including animals pretreated with retrorsine to exacerbate copper toxicosis and inhibit proliferation in native hepatocytes followed by partial hepatectomy to promote liver repopulation. Hepatocytes from normal, syngeneic LEA rats were transplanted intrasplenically. Animal survival, biliary copper excretion, and hepatic copper were determined. The magnitude of liver repopulation was demonstrated by measuring serum ceruloplasmin and hepatic atp7b mRNA. Long-term survival in LEC rats treated with retrorsine, partial hepatectomy, and cell transplantation was up to 90%, whereas fewer than 10% of animals pretreated with retrorsine, without cell therapy, survived, P < 0.001. Liver repopulation occurred gradually after cell transplantation, ranging from <25% at 6 weeks, 26 to 40% at 4 months, and 74 to 100% at 6 months or beyond. Liver repopulation restored biliary copper excretion capacity and lowered liver copper levels. Remarkably, liver histology was completely normal in LEC rats with extensive liver repopulation, compared with widespread megalocytosis, apoptosis, oval cell proliferation, and cholangiofibrosis in untreated animals. These data indicate that liver repopulation with functionally intact cells can reverse pathophysiological perturbations and cure Wilson's disease.
Parents should restrict children's use of mobile phones, report says
Authors: Madeleine Brettingham
Journal: BMJ (2005)

Parents need to be more cautious about allowing their children to use mobile phones, said a report launched by the National Radiological Protection Board this week.

The report is a continuation of work published in 2000 by the UK Independent Expert Group on Mobile Phones ( BMJ 2000;320: 1358), and although …
Abstract P2-01-07: Analysis of the relationship between breast cancer risk-related gene polymorphisms, ESR1/6q25.1-rs2046210 and mammographic breast density
Authors: T Nogami, N Taira, T Mizoo, K Nishiyama, T Iwamoto, T Motoki, T Shien, J Matsuoka, H Doihara, S Ishihara, H Kawai, K Kawasaki, Y Ogasawara, Y Ishibe
Journal: Cancer Research (2013)

Abstract Background: Based on the results of a case-control study performed in Japan (Okayama and Kagawa), it was revealed that gene polymorphisms of the estrogen receptor (single nucleotide polymorphisms, SNPs), ESR1/6q25.1-rs2046210 and rs3757318, were closely related to breast cancer risk in Japanese women, and that the odds ratios per allele of individual SNPs were 1.37 [95% CI: 1.1 - 1.7] and 1.33 [1.04 - 1.7], respectively (San Antonio Breast Cancer Symposium 2012, Mizoo et al.). To examine the effects of these SNPs on the pathogenic mechanism of breast cancer, we analyzed the relationship of SNPs with reproductive/physiological factors (age of menarche and number of births), physical factors (height and Body Mass Index [BMI]), family history and mammographic breast density. Methods: Among the patients enrolled in the case-control study, the patients who could be evaluated regarding their lifestyle, SNPs and mammographic breast density were divided into the case group (N = 394) and the control group (N = 511) as the dataset for the study. SNPs were analyzed using the TaqMan genotyping assay® for blood samples. In the analysis of the relationship between SNPs and breast cancer risk, the odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using logistic regression analysis. For the analysis of the relationship between SNPs and the factors, t-test and chi-square test were used. Results: In our dataset, the age-adjusted OR [95% CI] of ESR1/6q25.1-rs2046210 and rs3757318 were 2.22 [1.41 - 3.55] (AA vs. GG) and 2.12 [1.2 - 3.8] (AA vs. GG), respectively, suggesting that they would be significant risk factors. As a result of analyzing the relationship between SNPs and other factors, a significantly lower BMI was observed for the risk allele AA/AG of rs2046210, compared to GG (p = 0.014, t-test). Regarding the mammographic breast density, a significantly higher proportion of mammary glands with high density was confirmed for the risk allele AA/AG of rs2046210, compared to GG (p = 0.0389, chi-square test). The tendency towards a high mammographic breast density in the rs2046210 risk allele AA/AG was also confirmed based upon a stratified analysis of the case and control groups before and after menopause, and a significant correlation was observed, especially before menopause (p = 0.026, chi-square test). Conclusion: Mammographic high breast density is generally considered as one of the breast cancer risks, and it was suggested that gene polymorphisms of ESR1/6q25.1-rs2046210 might affect mammographic breast density. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-01-07.
Abstract 4221: Inhibition of hedgehog signaling by extracts of sutherlandia
Authors: Yuan Lu, Hui Lin, Sara K. Drenkhahn, Nicholas J.E. Starkey, Glenn A. Jackson, William Folk, Kevin L. Fritsche, Dennis B. Lubahn
Journal: Cancer Research (2011)

Abstract Many botanical compounds that have been proposed to prevent cancer may potentially work via inhibition of the hedgehog-signaling pathway. Here we investigated the potential of Sutherlandia frutescens (also called “cancer bush” in South Africa) to prevent and/or treat prostate cancer. We hypothesize that the anti-cancer effects of Sutherlandia are due to its inhibition of hedgehog-signaling pathway activity. To determine hedgehog pathway inhibitory activity, we treated Shh light II cells with multiple doses of a methanol extraction of Sutherlandia and measured Gli1 reporter activities. Results: We found that a methanol extract of Sutherlandia was able to inhibit hedgehog pathway activity in a dose-dependent manner as monitored by Gli reporter assay (IC50=1:4000). Moreover, the Sutherlandia extract can inhibit the growth of human prostate cancer cells PC3 and LNCaP with IC50 of 1:400 and 1:1500 fold dilutions, respectively. At these same extract dilutions normal prostate cancer cell growth was not inhibited. Our data indicate that Sutherlandia contains potent anti-cancer botanicals that have hedgehog inhibitory activity. Conclusion: Our results suggest that this plant offers a potentially cheap and effective alternative for hedgehog-driven cancer therapies. Additionally, Sutherlandia may yield novel targets that potentially could lead to a second generation hedgehog inhibitor, as resistance has been found to the first generation drugs currently in clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4221. doi:10.1158/1538-7445.AM2011-4221
Abstract ES05-2: Divergent trends in breast cancer subtypes, a manifestation of cancer heterogeneity
Authors: WF Anderson
Journal: Cancer Research (2013)

Abstract Recent studies in the United States show an unexpected divergence of ER positive and ER negative breast cancer incidence rates (JNCI 103: 1397-1402, 2011). ER positive cancers have risen while ER negative cancers have declined over the long-term. Divergent ER-specific trends might reflect statistical anomalies, lower assay thresholds for classifying breast cancers as ER positive, and/or the implementation of widespread screening mammography with increased sensitivity for ER positive cancers. However, the analysis of secular trends in Denmark, where there was better control of these potentially confounding factors, showed similar trends as in the United States (IJC 133: 2201-2206, 2013). ER positive cancers had increased among middle-aged and older Danish women in earlier birth-cohorts (or generations), implying a confluence of risk factor exposures during the peri- and the post-menopausal time periods of a woman's lifetime. In contrast, ER negative cancers had decreased among younger women in more recent birth-cohorts during the premenopausal time periods. Divergent ER-specific trends among different birth-cohorts in younger and older generations is consistent with breast cancer heterogeneity due to distinct etiologic pathways for ER positive and ER negative breast cancers, which could be due to trends in environmental and lifestyle risk factors with dual effects by ER expression. Two such possible risk factors are pregnancy (or parity) and obesity, which are decreasing and increasing, respectively, in both the United States and Denmark. For example, parity tends to reduce breast cancer risk for ER positive cancer and to increase risk for ER negative cancers. In fact, new breast cancer cases appear to be rising worldwide due to the consequences of changing reproductive, hormonal, and dietary risk factors. For this reason, it is plausible that the same risk factors or at the least risk factors acting through common mechanisms in the United States and Denmark may foreshadow a common pattern worldwide. This is good news since ER negative breast cancers are the most difficult to treat subtypes of breast cancer, especially the so-called triple negative cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES05-2.
Can behavioural economics make us healthier?
Authors: G. Loewenstein, D. A. Asch, J. Y. Friedman, L. A. Melichar, K. G. Volpp
Journal: BMJ (2012)

Behavioural economics is becoming increasingly popular as a way to improve public health. <b>George Loewenstein and colleagues</b> point out some of the pitfalls and warn that it cannot be used as a substitute for conventional policies to tackle fundamental problems
Postmortem Analysis and Retrieval of Implantable Pacemakers and Defibrillators
Authors: James N. Kirkpatrick, Martin C. Burke, Bradley P. Knight
Journal: New England Journal of Medicine (2006)

To the Editor: Recent recalls of implantable pacemakers and defibrillators have cast a spotlight on the need for improved product reliability.1 Although it is estimated that the failure rate of these devices is low, the true rate of device malfunction is not known. The Food and Drug Administration recently stated that it supports a policy requiring that defibrillators be returned to the manufacturer to be studied for possible defects after the death of a patient.2 The few published guidelines available for morticians concerning the handling of devices make no mention of routine interrogation or retrieval.3,4 Therefore, we surveyed embalmers . . .
Television epilepsy and pattern sensitivity.
Authors: S B Stefansson, C E Darby, A J Wilkins, C D Binnie, A P Marlton, A T Smith, A V Stockley
Journal: BMJ (1977)

Properly functioning domestic television sets may induce seizures in epileptic patients (TV epilepsy). We investigated the effects of different types of visual stimuli on paroxysmal electroencephalographic (EEG) activity in 32 patients known to be sensitive to intermittent photic stimulation (stroboscopic light). We monitored sensitivity to patterns of horizontal and vertical lines, both stationary and vibrated (pattern sensitivity), and to normal broadcasts on a domestic, black and white (405- or 625-line) TV receiver (TV sensitivity). Twenty-three of the 32 patients were sensitive to pattern. Twenty-two were sensitive to vibrated patterns, and 11 to static patterns (P less than 0-01), All patients sensitive to pattern were also sensitive to TV; The association between sensitivity to pattern and to TV was significant. Clinical history of TV epilepsy (16 out of 32 patients) and laboratory evidence of pattern or TV sensitivity were not significantly associated. The high incidence of pattern sensitivity among flicker-sensitive patients and its association with TV sensitivity suggests that linear patterns produced by the raster of a black and white set as it scans, or "line-jitter" produced by the raster in areas of low TV-signal strength may contribute to the epileptogenic effect of TV.
INTRAPERITONEAL TRANSFUSION WITH CITRATED BLOOD
Authors: J. MARTIN SANSBY
Journal: JAMA (1923)

The difficulties encountered in the transfusion of blood in infancy and early childhood have prompted numerous investigators to attempt other simpler procedures. Consequently, the use of blood in infants and children has been confined until recently to (1) subcutaneous or intramuscular injection of blood; (2) the introduction of blood into one of the larger peripheral veins, and (3) transfusion into the superior longitudinal sinus.  The subcutaneous or intramuscular injection of blood, which is now used chiefly in the treatment of hemorrhagic disease of the new-born, was at one time considered effective in conditions in which a transfusion was indicated. That this method is not in a strict sense a blood transfusion is substantiated by Taylor, 1 who found that only a small number of the cells so injected ever reach the circulation.  Transfusion by the use of one of the larger peripheral veins has been attended in many cases with
Screening for cervical cancer.
Authors: A. J. Lucas, M. Glover, M. E. Attwood
Journal: BMJ (1968)

difficult exchange transfusion.In the first of these two cases there was a positive blood culture for E. coli associated with bowel necrosis extending from the caecum to the descending colon.Our second case had diar- rhoea for seven days, which preceded the onset of abdominal distension and peripheral circu- latory collapse owing to necrosis and perfora- tion of the terminal ileum only.Unfortunately both these infants died without laparo- tomy being undertaken, and at necropsy we were able to demonstrate antemortem thrombi in the ductus venosus and portal vein in the first and in the portal and splenic veins in the second.We note that in the series quoted there is no comment on the state of the portal vein in those infants who died.A fuller report is being prepared for publication.-Weare, etc.,
Placental corticotropin-releasing hormone may be a stimulator of maternal pituitary adrenocorticotropic hormone secretion in humans.
Authors: A Sasaki, O Shinkawa, K Yoshinaga
Journal: Journal of Clinical Investigation (1989)

To clarify the physiological role of placental corticotropin-releasing hormone (CRH), we measured plasma CRH, ACTH, and cortisol throughout pregnancy. Cerebrospinal fluid (CSF) CRH levels and ACTH responsiveness to synthetic CRH were also quantified in pregnant and nonpregnant women. Maternal plasma CRH levels, which increased progressively during pregnancy, correlated well with both ACTH and cortisol in early labor, delivery, and postpartum samples, and also with cortisol levels in samples before labor. CSF CRH levels in term pregnant women did not differ from those of nonpregnant women. CRH infusion that attained similar plasma CRH levels to those found in late pregnancy elicited significant ACTH release in vivo and regular CRH test provoked normal ACTH response during early pregnancy but no response during late pregnancy. We concluded that: (a) maternal pituitary-adrenal axis correlates well with plasma CRH levels, which are high enough to provoke ACTH release from maternal pituitary; (b) hypothalamic CRH secretion in term pregnant women is not exaggerated; and (c) maternal pituitary is responsive to synthetic CRH in early but not late pregnancy, suggesting that maternal pituitary-adrenal axis is already activated by high circulating CRH. Placental CRH may be an important stimulator of the maternal pituitary-adrenal axis during pregnancy.
Idiopathic Pulmonary Ossification with Focal Pulmonary Uptake of Technetium-99m HMDP Bone Scanning Agent
Authors: EDWARD B. SILBERSTEIN, PRASAN J. VASAVADA, HUGH HAWKINS
Journal: Clinical Nuclear Medicine (1985)

A case of idiopathic pulmonary ossification is presented in an asymptomatic, middle-aged woman with typical chest x-ray changes and corresponding localization of technetium diphosphonate. In this condition, mature bone is found in the pulmonary parenchyma. The etiology is unknown.
Protein kinase cascades in the regulation of cardiac hypertrophy
Authors: Gerald W. Dorn, Thomas Force
Journal: Journal of Clinical Investigation (2005)

In broad terms, there are 3 types of cardiac hypertrophy: normal growth, growth induced by physical conditioning (i.e., physiologic hypertrophy), and growth induced by pathologic stimuli. Recent evidence suggests that normal and exercise-induced cardiac growth are regulated in large part by the growth hormone/IGF axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive cardiac growth is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phospholipase C pathway, leading to an increase in cytosolic calcium and activation of PKC. Here we review recent developments in the area of these cardiotrophic kinases, highlighting the utility of animal models that are helping to identify molecular targets in the human condition.
Autism-Associated Promoter Variant in MET Impacts Functional and Structural Brain Networks
Authors: Jeffrey D. Rudie, Leanna M. Hernandez, Jesse A. Brown, Devora Beck-Pancer, Natalie L. Colich, Philip Gorrindo, Paul M. Thompson, Daniel H. Geschwind, Susan Y. Bookheimer, Pat Levitt, Mirella Dapretto
Journal: Neuron (2012)
Volume regulation in children with early relapse of minimal-change nephrosis with or without hypovolaemic symptoms
Authors: J.G. Vande Walle, R.A.M.G. Donckerwolcke, J.W. van Isselt, J.A. Joles, H.A. Koomans, F.H.M. Derkx
Journal: The Lancet (1995)
Skin Tearing During Corticosteroid Therapy
Authors: Robert Pool
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The article entitled "Spontaneous Skin Tearing During Systemic Corticosteroid Treatment" by Gottlieb and Penneys (243:1260, 1980) is interesting but in no way proves that the skin lesion demonstrated in the authors' photographs was actually spontaneous or that the tearing was caused solely by steroid therapy. The patient described was receiving treatment with steroids as well as with aspirin and had a prolonged bleeding time—a combination that indeed can promote purpuric lesions under the thin skin of the upper or lower extremities of a patient with rheumatoid arthritis. Minor trauma to this skin can produce a purpuric bleb that is a subepidermal or subdermal hematoma. The skin becomes separated from its vascular tree and diminishes in thickness to that of a split-thickness epidermal graft. At this stage it can be torn with the slightest trauma, such as crossing the lower legs. In fact, I have seen this on
Scientist sues Nobel assembly for awarding medicine prize to wrong people
Authors: C. Dyer
Journal: BMJ (2012)

The body that awards the Nobel prize for physiology or medicine is being sued for defamation by a researcher who alleges that the two scientists jointly awarded this year’s prize have been wrongly credited with work he did a decade before.

Rongxiang Xu, a Chinese scientist working in California, filed the lawsuit at the Superior Court of California, Orange County.

This year’s prize has gone to John Gurdon, of the Gurdon Institute …
OC-081 Genetic polymorphisms and patterns of FGF19 response to meals in primary bile acid diarrhoea
Authors: I Johnston, S S Pattni, J Lin, T Dew, P H Dixon, J R Walters
Journal: Gut (2012)

<h3>Introduction</h3> Primary bile acid diarrhoea (PBAD) is associated with low median serum fibroblast growth factor 19 (FGF19) levels. Our group has suggested that PBAD results from impaired negative feedback by FGF19 on the enzyme CYP7A1, leading to over production of bile acids, which spill over into the colon leading to diarrhoea. We aim to characterise abnormalities in FGF19 in PBAD, in particular the response of the hormone to meal stimuli and to describe phenotypic patterns of response. We have explored possible associations of genetic polymorphisms with both PBAD and specific phenotypes. <h3>Methods</h3> Subjects with PBAD were prospectively recruited. After an overnight fast, blood was sampled every 90 min for 6 h. Meals were provided at 9:00 and 12:00. Serum FGF19 was quantified by ELISA using a commercially available kit. Three phenotypes of meal stimulated FGF19 response are described: 1. Low-low (L-L) all five serum FGF19 levels &lt;400 pg/ml. 2. Low-high (L-H) sample 1 400 pg/ml sample 4 or 5 &gt;400 pg/ml. 3. High-high (H-H) samples 1 and 3 or 5 &gt;300 pg/ml. In a separate part of the study genomic DNA was extracted from 91 subjects with PBAD and 120 diarrhoea control subjects. Eight SNPs were analysed, two from the FXR gene (rs61755050, rs56163822), two from the FGF19 gene (rs1789170, rs948992) as well as SNPs from the genes for OSTα, klothoβ, FGFR4 and ASBT (rs939885, rs17618244, rs376618, rs188096). Genotyping was performed using Taqman SNP genotyping assays. <h3>Results</h3> 18 subjects underwent serial FGF19 sampling. Seven were defined as L-L response, five as L-H and four as H-H. Two subjects did not match criteria for the subtypes. The seven L-L subjects had lower SeHCATs compared with L-H and H-H combined (p&lt;0.05). Five subjects had SeHCATs of &lt;5%, all but one were L-L. Overall, subjects with lower SeHCATs had lower FGF19 levels. Area under the curve was lower for those with SeHCAT &lt;5% than those above (median 701 pg/ml h vs 1655 pg/ml h p=0.023). The FGF19 level at 1.5 h correlated with subjects9 SeHCAT (r=0.49, p=0.04). The ASBT SNP was associated with L-L subjects, present in four out of seven (p&lt;0.05). No other significant SNP associations were found within the phenotypes described nor between PBAD as a whole and diarrhoea controls. <h3>Conclusion</h3> Serial FGF19 sampling in PBAD identified three responses to meal stimulus. Most individuals with severe PBAD have L-L response of FGF19, and most of these have a polymorphism in the gene for ASBT. L-H and H-H phenotypes are seen in those with higher SeHCATs. The L-H pattern resembles that previously reported in healthy individuals. These patterns may represent a defect in the receptor component of the feedback mechanism for BA synthesis. <h3>Competing interests</h3> None declared.
Blending With Surroundings, 'NAMRU' Aids Hosts While Studying Disease Threats to US Military
Authors: Chris Raymond
Journal: JAMA (1989)

FEW AMERICAN MILITARY bases have a mosque. In Cairo, Egypt, the US Navy actually constructed one a few years ago on the grounds of its Medical Research Unit there. That, as much as anything, symbolizes the unique working relationship between the unit and the Egyptian government. Since 1948, through international diplomatic relations smooth or strained, the Navy has been conducting research into local infectious diseases that it considers potential "war stoppers" capable of putting an army out of action, research that simultaneously has contributed to the health objectives of the Egyptian government. <h3>Africa, Pacific, Latin America</h3> Assignment to the Naval Medical Research Unit Number 3, or NAMRU, as the facility is known, is a plum for physicians interested in tropical diseases. (Besides the unit in Cairo, which oversees research in Egypt, the Sudan, Kenya, North Yemen, Djibouti, and Ethiopia, the Navy also has similar units in Manila, Djakarta, and Peru.)