tbuckley/cabot-search huggingface dataset:
Founders, Drift, and Infidelity: The Relationship between Y Chromosome Diversity and Patrilineal Surnames
Authors: T. E. King, M. A. Jobling
Journal: Molecular Biology and Evolution (2009)

Most heritable surnames, like Y chromosomes, are passed from father to son. These unique cultural markers of coancestry might therefore have a genetic correlate in shared Y chromosome types among men sharing surnames, although the link could be affected by mutation, multiple foundation for names, nonpaternity, and genetic drift. Here, we demonstrate through an analysis of 1,678 Y-chromosomal haplotypes within 40 British surnames a remarkably high degree of coancestry that generally increases as surnames become rarer. On average, the proportion of haplotypes lying within descent clusters is 62% but ranges from 0% to 87%. The shallow time depth of many descent clusters within names, the lack of a detectable effect of surname derivation on diversity, and simulations of surname descent suggest that genetic drift through variation in reproductive success is important in structuring haplotype diversity. Modern patterns therefore provide little reliable information about the original founders of surnames some 700 years ago. A comparative analysis of published data on Y diversity within Irish surnames demonstrates a relative lack of surname frequency dependence of coancestry, a difference probably mediated through distinct Irish and British demographic histories including even more marked genetic drift in Ireland.
Modernising mental health services
Authors: J. Sharkey, P. Johnstone, C. Allot, V. Hawkins, J. Moncrieff, P. Thomas, M. Crawford, C. Henderson, T. Johnston
Journal: BMJ (1999)

# Personality disorders are arbitrary medicalisation of human variation {#article-title-2} EDITOR—Over the past few months the issue of personality disorder has come up several times, most recently in Marshall's editorial on Modernising Mental Health Services .1 It seems that the reporting of the Michael Stone case fuelled the madness or badness argument to the point that the home secretary chose, in the usual populist rhetoric, “to take a pop” at psychiatrists. The difficulty with personality disorders is that, by their nature, they are an arbitrary and subjective medicalisation of human variation. It is hardly surprising that they are often not amenable to treatment. A supervising consultant psychiatrist once asked me to name any psychiatrist I knew who did not have a personality disorder. When I considered this poisoned chalice and declined to reply, he said a person without a personality disorder is a person without a personality. If personality disorder is sufficient legal grounds to detain someone, some questions need answering: when should he or she be released, and does the duration of detention fit the crimes committed or is it a value call for the psychiatrist? We find ourselves in difficult ideological times if society cannot cope with the less savoury aspects of human variation. The profession should be bigger than to fall for the myth, driven by tabloid headlines, of a safe society. 1. ↵1. Marshall M .Modernising mental health services.BMJ1999; 318:3–4. (2 January.) [OpenUrl][1][FREE Full Text][2] # Strategy does not seem to be based on systematic evidence {#article-title-4} EDITOR—We were surprised to see that the government's plans for modernising the NHS mental health services are not based on any of the findings from its own research and development programme.1 Although we appreciate that these are “emerging findings” … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DMarshall%26rft.auinit1%253DM.%26rft.volume%253D318%26rft.issue%253D7175%26rft.spage%253D3%26rft.epage%253D4%26rft.atitle%253DModernising%2Bmental%2Bhealth%2Bservices%26rft_id%253Dinfo%253Apmid%252F9872860%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=318/7175/3&atom=%2Fbmj%2F318%2F7186%2F806.2.atom
ETIOLOGY OF OROYA FEVER
Authors: Hideyo Noguchi, Henry R. Muller, Evelyn B. Tilden, Joseph R. Tyler
Journal: The Journal of Experimental Medicine (1929)

Experiments are reported on the effect upon the course of experimental verruga peruana in Macacus rhesus of the injection of (1) small quantities of rabbit immune serum simultaneously with living cultures, (2) one large dose of convalescent monkey serum 24 hours prior to inoculation, (3) a similar preliminary dose followed by three subsequent injections of the serum, (4) three large doses of convalescent serum, following the inoculation. The convalescent serum was found (1) to prevent the multiplication of Bartonella bacilliformis in the blood in most instances, and (2) to delay the development of the skin lesions for considerable periods, when given before inoculation. When the serum treatment was not begun until after the appearance of the skin lesions, it had no effect on the progress of the nodules, although the blood became free from Bartonella bacilliformis. Since the severe effects of verruga peruana (Carrion's disease) are believed to be due to the multiplication of Bartonella bacilliformis within the blood, the injection of convalescent serum in cases of Carrion's disease in man would appear to offer promise.
Special Features of Intestinal Metaplasia and Its Relation to Early Gastric Carcinoma in Man: Observation by a Method in Which Leucine Aminopeptidase Activity Is Used&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Kunihiro Nakahara
Journal: JNCI Journal of the National Cancer Institute (1978)

The degree of intestinal metaplasia and its macroscopic distribution in gastric mucosa were examined by a new method in which leucine aminopeptidase (LAP) activity is used to investigate the relationship between intestinal metaplasia and gastric carcinoma. Since LAP is a specific enzyme of intestinal metaplasia, the area showing positive reaction for this enzyme corresponds strictly with the zone of intestinal metaplasia examined microscopically. Almost all metaplasia was demonstrated by this method. This method was used to examine 40 human gastric carcinomas confined to the mucosa. Gastric mucosa containing differentiated tubular-type carcinoma (60%) was associated with a high degree of metaplasia in comparison with the low degree of metaplasia in poorly differentiated carcinoma (40%). Differentiated tubular-type carcinoma was closely related to intestinal metaplasia. However, all carcinomas arising from the mucosa without intestinal metaplasia (18%) were poorly differentiated. Therefore, gastric carcinomas occurring in Japanese patients are frequently and closely related to intestinal metaplasias.
Defensins. Natural peptide antibiotics of human neutrophils.
Authors: T Ganz, M E Selsted, D Szklarek, S S Harwig, K Daher, D F Bainton, R I Lehrer
Journal: Journal of Clinical Investigation (1985)

We extracted a granule-rich sediment from normal human neutrophils and subjected it to chromatographic, electrophoretic, and functional analysis. The extract contained three small (molecular weight less than 3,500) antibiotic peptides that were named human neutrophil peptide (HNP)-1, HNP-2, and HNP-3, and which will be referred to as "defensins." HNP 1-3, a mixture of the three defensins, killed Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli effectively in vitro when tested in 10 mM phosphate buffer containing certain nutrients, but it had little or no bactericidal activity in nutrient-free buffer. In contrast, the nutrient-free buffer supported a high degree of activity by HNP 1-3 against Cryptococcus neoformans. In addition to its antibacterial and antifungal properties, HNP 1-3 directly inactivated herpes simplex virus, Type 1. Two of the individual purified defensins, HNP-1 and HNP-2, were as microbicidal as the mixture HNP 1-3. HNP-3 was less active than the other defensins against most but not all of the microbes tested. Immunoperoxidase stains revealed HNP 1-3 to have a granular localization in the neutrophil's cytoplasm by light microscopy. Frozen thin section immunogold transmission electron microscopy showed HNP 1-3 to be localized in azurophil granules. These studies define a broad-spectrum antimicrobial system in human neutrophils. The defensin system may operate in conjunction with or independently from oxygen-dependent microbicidal processes to enable human neutrophils to inactivate and destroy potential pathogens.
Molecular Causes of the Aberrant Choline Phospholipid Metabolism in Breast Cancer
Authors: Kristine Glunde, Chunfa Jie, Zaver M. Bhujwalla
Journal: Cancer Research (2004)

Abstract Proton magnetic resonance spectroscopy (1H MRS) consistently detects significant differences in choline phospholipid metabolites of malignant versus benign breast lesions. It is critically important to understand the molecular causes underlying these metabolic differences, because this may identify novel targets for attack in cancer cells. In this study, differences in choline membrane metabolism were characterized in breast cancer cells and normal human mammary epithelial cells (HMECs) labeled with [1,2-13C]choline, using 1H and 13C magnetic resonance spectroscopy. Metabolic fluxes between membrane and water-soluble pool of choline-containing metabolites were assessed by exposing cells to [1,2-13C]choline for long and short periods of time to distinguish between catabolic and anabolic pathways in choline metabolism. Gene expression analysis using microarrays was performed to understand the molecular mechanisms underlying these changes. Breast cancer cells exhibited increased phosphocholine (PC; P &amp;lt; 0.001), total choline-containing metabolites (P &amp;lt; 0.01), and significantly decreased glycerophosphocholine (P &amp;lt; 0.05) compared with normal HMECs. Decreased 13C-enrichment was detected in choline (P &amp;lt; 0.001) and phosphocholine (P &amp;lt; 0.05, P &amp;lt; 0.001) of breast cancer cells compared with HMECs, indicating a higher metabolic flux from membrane phosphatidylcholine to choline and phosphocholine in breast cancer cells. Choline kinase and phospholipase C were significantly overexpressed, and lysophospholipase 1, phospholipase A2, and phospholipase D were significantly underexpressed, in breast cancer cells compared with HMECs. The magnetic resonance spectroscopy data indicated that elevated phosphocholine in breast cancer cells was primarily attributable to increased choline kinase activity and increased catabolism mediated by increased phospholipase C activity. These observations were consistent with the overexpression of choline kinase and phospholipase C detected in the microarray analyses.
Antibiotics in acute exacerbations of COPD: the good, the bad and the ugly
Authors: Wim G. Boersma
Journal: European Respiratory Journal (2012)

ou may well wonder what the connection might be between the title of this editorial and the famous Western The Good, the Bad and the Ugly.Well, we know that antibiotics are effective in treating bacterial infections (the good), are not as harmless as both clinicians and patients may think (the bad), and may have adverse effects and do not work in viral infections (the ugly).There is an increasing awareness that we have to challenge the problems caused by the overuse of antibiotics.Beliefs, expectations and incentives are the drivers of antibiotic overuse among the concerned parties: patients, physicians and society.Therefore, social norms would have to be altered, resulting in a fundamental change in patients' expectations, marketing, indications for antibiotic use and, particularly, physicians' prescription behaviour.In a recent paper by the McDonnell Norms Group [1], some radical solutions were suggested, ranging from ''changes in the way physicians are paid for prescribing antibiotics'' and ''looking at accuracy and limitation of antibiotic use'' to ''patients might be reimbursed differently for antibiotic prescriptions''.Antibiotic resistance is inevitably related to excessive antibiotic use.The frequency of antibiotic resistance in bacteria among different countries is proportional to their relative rate of antibiotic use [2].This is generally expressed in defined daily doses per 1,000 inhabitants per day (DID).Countries in southern and eastern Europe have the highest DID, whereas consumption is much lower in northern Europe [1,3].Antibiotic consumption differs among various countries in Europe.In 2008, the proportion of outpatient penicillin use ranged from 30.1% in Germany to 62.6% in Denmark, whereas the proportional use of quinolones ranged from 3.1% in the UK to 17.0% in Russian.Efforts to control overprescribing of antibiotic use can be successful, as has been shown in studies from Finland and Iceland.Reduction in resistance (up to 30%) can be achieved by implementing specific recommendations that discourage antibiotic treatment [4,5].
Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors.
Authors: S Tanaka, N Takahashi, N Udagawa, T Tamura, T Akatsu, E R Stanley, T Kurokawa, T Suda
Journal: Journal of Clinical Investigation (1993)

The mechanism of action of macrophage colony-stimulating factor (M-CSF) in osteoclast development was examined in a co-culture system of mouse osteoblastic cells and spleen cells. In this co-culture, osteoclast-like multinucleated cells (MNCs) were formed within 6 d in response to 10 nM 1 alpha,25(OH)2D3 added only for the final 2 d of culture. Simultaneously adding hydroxyurea for the final 2 d completely inhibited proliferation of cultured cells without affecting 1 alpha,25(OH)2D3-stimulated MNC formation. Autoradiographic examination using [3H]-thymidine revealed that osteoclast progenitors primarily proliferated during the first 4 d, whereas their differentiation into MNCs occurred predominantly during the final 2 d of culture in response to 1 alpha,25(OH)2D3. When anti-M-CSF antibody or anti-M-CSF receptor antibody was added either for the first 4 d or for the final 2 d, the MNC formation was similarly inhibited. In co-cultures of normal spleen cells and osteoblastic cells obtained from op/op mice, which cannot produce functionally active M-CSF, the lack of M-CSF either for the first 4 d or for the final 2 d failed to form MNCs in response to 1 alpha,25(OH)2D3 added for the last 2 d. These results clearly indicate that M-CSF is indispensable for both proliferation of osteoclast progenitors and their differentiation into mature osteoclasts.
Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions
Authors: Armando Bartolazzi, Alessandra Gasbarri, Mauro Papotti, Gianni Bussolati, Teresina Lucante, Ashraf Khan, Hidenori Inohara, Ferdinando Marandino, Fabio Orlandi, Francesco Nardi, Aldo Vecchione, Raffaele Tecce, Olle Larsson
Journal: The Lancet (2001)
Occupational asthma due to polyethylene shrink wrapping (paper wrapper's asthma).
Authors: P F Gannon, P S Burge, G F Benfield
Journal: Thorax (1992)

Occupational asthma due to the pyrolysis products of polyvinyl chloride (PVC) produced by shrink wrapping processes has previously been reported. The first case of occupational asthma in a shrink wrap worker using a different plastic, polyethylene, is reported; the association was confirmed by specific bronchial provocation testing.
Thoughts on the Role of the Healing Professions and the Events of September 11, 2001
Authors: Donald Baim, Thomas J. Brady, S. Ward Casscells, Michael Dunne, Zahi Fayad, Valentin Fuster, Scott Gazelle, Alan Heldman, Thomas Hatsukami, Scott Kinlay, Antoine Lafont, Richard Lee, Peter Libby, Bernhard Meier, James E. Muller, Morteza Naghavi, Christopher O’Donnell, Emerson Perin, Mark Rekhter, John Rumberger, Mary Russell, Robert Schwartz, Andrew Selwyn, H. William Strauss, Gary Tearney, Takanobu Tomaru, E. Muran Tuzcu, Bruce Wasserman
Journal: Circulation (2002)
Long-term endocrine side effects of childhood Hodgkin's lymphoma treatment: a review
Authors: W. van Dorp, R. D. van Beek, J. S. E. Laven, R. Pieters, S. M. P. F. de Muinck Keizer-Schrama, M. M. van den Heuvel-Eibrink
Journal: Human Reproduction Update (2011)

Since childhood cancer survival has increased, long-term effects of treatment have gained interest. Childhood Hodgkin's lymphoma has been treated successfully for decades now. We provide an overview of the literature on long-term endocrine side effects, such as gonadal dysfunction and growth retardation, as a result of childhood Hodgkin's lymphoma treatment. A comprehensive search of the Pubmed database was performed. We identified 16 studies (10 studies: 298 male survivors and 6 studies: 230 female survivors) about gonadal dysfunction. In survivors treated with alkylating agents or pelvic radiotherapy, severe gonadal damage is described. Recovery was rarely described. Seven studies (481 survivors) about bone mineral density (BMD) and growth were identified. The effects on BMD appear to be small. Data on growth are scarce, but show that radiotherapy in a dose of >30 Gy including the spine, especially in pre-pubertal children, results in reduced height. We included 10 studies (4012 survivors) about thyroid complications. Hypothyroidism is the most common thyroid disorder after radiotherapy. There is also a significant incidence in thyroid carcinoma after low-dose radiation. In survivors treated with chemotherapy only, hypothyroidism and thyroid cancer have not been reported. The severity of endocrine toxicity after childhood Hodgkin's lymphoma depends on the type of treatment. Gonadal dysfunction seems to be the most severe endocrine long-term effect, especially after treatment with alkylating agents or pelvic radiotherapy. The knowledge obtained in specific follow-up programmes for paediatric cancer survivors will help to find the optimal balance between curability and long-term side effects.
Iron and Hepatic Uroporphyrin Synthesis
Authors: Bertram F. Felsher
Journal: JAMA (1973)

Of 58 patients with porphyria cutanea tarda (PCT), hypersideremia occurred in 17. Stainable iron was present in the liver specimens of 16 in 20. Iron concentration was slightly increased in five biopsy specimens and markedly in one. Packed red blood cell phlebotomies resulted in remissions in all of six patients. Repletion of iron stores by administering iron to two patients in phlebotomy-induced remissions resulted in biochemical relapses six and nine months later; whereas remissions were sustained for at least one year in 24 other patients.
Superoxide Is Involved in the Central Nervous System Activation and Sympathoexcitation of Myocardial Infarction–Induced Heart Failure
Authors: Timothy E. Lindley, Marc F. Doobay, Ram V. Sharma, Robin L. Davisson
Journal: Circulation Research (2003)

Increased angiotensin II signaling in the brain has been shown to play a critical role in the excessive sympathoexcitation and development of heart failure (HF) after myocardial infarction (MI). We have recently demonstrated that reactive oxygen species mediate the actions of angiotensin II in the brain. In this study, we tested the hypothesis that increased redox signaling in central cardiovascular control regions is a key mechanism in the neurocardiovascular dysregulation that follows MI. Ligation of the left coronary artery induced a large MI and subsequent HF in adult C57BL/6 mice, as demonstrated by cardiac hypertrophy, hydrothorax, and ascites. Immunohistochemical analysis of Fos, a marker of neuronal activation, revealed a significant increase in the number of Fos-positive neurons in the paraventricular nucleus and supraoptic nucleus at 2 and 4 weeks after MI compared with sham mice. Intracerebroventricular injection of an adenoviral vector encoding superoxide dismutase (Ad-Cu/ZnSOD) caused a significant decrease in the number of Fos-positive neurons in the paraventricular nucleus and supraoptic nucleus at 2 weeks after MI compared with mice receiving either saline or a control vector (Ad-LacZ). There was also a diminished role of sympathetic drive in post-MI mice treated centrally with Ad-Cu/ZnSOD, as demonstrated by significantly attenuated falls in heart rate and mean arterial pressure to the ganglionic blocker hexamethonium and decreased urinary norepinephrine levels in these mice compared with Ad-LacZ–treated MI mice. These results suggest that superoxide plays a key role in the central activation and sympathetic hyperactivity after MI in mice and that oxygen radicals in the brain may be important new targets for therapeutic treatment of heart failure.
A Novel Human-Specific Soluble Vascular Endothelial Growth Factor Receptor 1
Authors: Shay Sela, Ahuva Itin, Shira Natanson-Yaron, Caryn Greenfield, Debra Goldman-Wohl, Simcha Yagel, Eli Keshet
Journal: Circulation Research (2008)

A human-specific splicing variant of vascular endothelial growth factor (VEGF) receptor 1 (Flt1) was discovered, producing a soluble receptor (designated sFlt1-14) that is qualitatively different from the previously described soluble receptor (sFlt1) and functioning as a potent VEGF inhibitor. sFlt1-14 is generated in a cell type-specific fashion, primarily in nonendothelial cells. Notably, in vascular smooth muscle cells, all Flt1 messenger RNA is converted to sFlt1-14, whereas endothelial cells of the same human vessel express sFlt1. sFlt1-14 expression by vascular smooth muscle cells is dynamically regulated as evidenced by its upregulation on coculture with endothelial cells or by direct exposure to VEGF. Increased production of soluble VEGF receptors during pregnancy is entirely attributable to induced expression of placental sFlt1-14 starting by the end of the first trimester. Expression is dramatically elevated in the placenta of women with preeclampsia, specifically induced in abnormal clusters of degenerative syncytiotrophoblasts known as syncytial knots, where it may undergo further messenger RNA editing. sFlt1-14 is the predominant VEGF-inhibiting protein produced by the preeclamptic placenta, accumulates in the circulation, and hence is capable of neutralizing VEGF in distant organs affected in preeclampsia. Together, these findings revealed a new natural VEGF inhibitor that has evolved in humans, possibly to protect nonendothelial cells from adverse VEGF signaling. Furthermore, the study uncovered the identity of a VEGF-blocking protein implicated in preeclampsia.
Comparison of Strategies for Sustaining Weight Loss&lt;subtitle&gt;The Weight Loss Maintenance Randomized Controlled Trial&lt;/subtitle&gt;
Authors: Laura P. Svetkey
Journal: JAMA (2008)

EARLY TWO-THIRDS OF US adults are overweight or obese. 1 Together overweight and obesity are the second leading cause of preventable death, primarily through effects on car-diovascular disease (CVD) risk factors (hypertension, dyslipidemia, and type 2 diabetes). 2][5][6][7][8] Relatively short-term (ie, 4-6 months) behavioral interventions for adults re-sult in clinically significant weight loss, but regain is an intractable problem.
Use of a WHO-recommended algorithm to reduce mortality in seriously ill patients with HIV infection and smear-negative pulmonary tuberculosis in South Africa: an observational cohort study
Authors: Timothy H Holtz, Gaëtan Kabera, Thuli Mthiyane, Tainos Zingoni, Sidhambaram Nadesan, Douglas Ross, Jennifer Allen, Sekai Chideya, Henry Sunpath, Roxana Rustomjee
Journal: The Lancet Infectious Diseases (2011)
Effect of Epoetin on Survival in Patients With Breast Cancer
Authors: Giovanni Codacci-Pisanelli, Gian Paolo Spinelli, Silverio Tomao
Journal: Journal of Clinical Oncology (2008)

AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES 1. Mocellin S, Pilati P, Lise M, et al: Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal coacer: The end of an era? J Clin Oncol 25:5649-5654, 2007 2. Pestalozzi BC, Gruttadauria S, Clavien P-A: Hepatic arterial infusion: The beginning of the combination era. J Clin Oncol 26:2230-2231, 2008