tbuckley/cabot-search huggingface dataset:
Vitamin B<sub>6</sub>and Glucocorticoid Action*
Authors: MARK M. COMPTON, JOHN A. CIDLOWSKI
Journal: Endocrine Reviews (1986)

THE MECHANISMS by which steroid hormones interact with target tissues to induce endocrine responses have been studied since the early 1960's (for a recent review see Ref. 1), and many contributions have added to our current understanding of steroid hormone action. In essence, it is believed that the lipophilic steroid hormones enter target tissues by passively diffusing across the cell membrane. Once inside the cell, steroids bind reversibly to cytosolic receptor proteins in a stereospecific fashion to form steroid-receptor complexes. The actual localization of these receptors in the cytoplasm of target cells is a controversial subject (2); however, for the purposes of this discussion, it will be assumed that these receptors are available for steroid binding in the cytoplasmic compartment of the cell. This complex then undergoes a physicochemical transformation, termed activation, which enables the complex to bind tightly to appropriate chromatin acceptor sites. The phenomenon of steroid receptor activation is an incompletely understood process, but it can be simulated in vitro by a variety of techniques including warming of the receptor preparation from 0–25 C, exposure of the receptor complex to a high ionic strength environment, or dilution of the cytosol. After activation, the steroidreceptor complex associates tightly with the nucleus and binds to nuclear acceptor sites which probably consist of DNA and/or protein. This interaction between the receptor complex and chromatin results in the transcription of specific messenger RNAs that are subsequently translated into steroid-induced proteins.
Thrombosis and fibrinogen degradation products.
Authors: H. K. Basu, G. F. Williamson
Journal: BMJ (1969)

It is regrettable that P.E.F.measure- ments continue ito be popular among clini- cians,' despite warnings about their relative lack of sensitivity in assessing airway obstruc- tion published in your columns years ago.2'More recent studies which have clarified the relationship between lung volume, expiratory flow rate, and alveolar pressure' 5 substanti- ate the view that "The measurement of the maximal expiratory flow rate . . .cannot be recommended as a single lung function test."'Maximum expiratory flow rates depend on lung volume, and flow rates at small lung volumes are more depressed under conditions of peripheral airway obstruction than P.E.F.5 7 ' Leuallen and Fowler' realized this fact long ago, when they introduced the measurement of mid-expiratory flow rate.Measurement of spirometric values such as the F.E.V.1 or mid-expiratory flow rate, or recordings of maximum expiratory flow- volume curves, all include, directly or indirectly; information on maximum flows occurring at smaller lung volumes than that at which P.E.F. is reached.Any one of these methods would have indicated the severity of the persistent airway obstruction in the patient of Dr. Gregg and Dr. Batten more adequately than P.E.
Symmetrical pigmented sclerosis enclosed by pruritic erythema: a new variant of morphoea?
Authors: H. Minato, R. Taki, Y. Miyachi, A. Utani
Journal: British Journal of Dermatology (2009)

Conflicts of interest: none declared. Sir, Generalized morphoea (GM) is a subtype of morphoea with multiple sclerotic lesions lacking systemic involvement. During the 1950s to 1970s, GM was reported as large, pigmented sclerotic plaques that were distributed symmetrically.1 2–3 Since then, the number of isolated sclerotic lesions was introduced as part of the diagnostic criteria, and there have been reports of a high incidence of antinuclear antibodies associated with GM.4, 5 In general, GM consists of multiple (more than five or six), small (approximately palm size or smaller) sclerotic plaques and accounts for 8–9% of cases of morphoea.6 We present a patient with large, symmetrical, pigmented sclerotic lesions enclosed by pruritic erythema. The patient, a healthy 30‐year‐old woman, first noticed an area of pruritic erythema on the lumbar region of her back 2 years prior to our initial evaluation. New pruritic erythematous lesions appeared within several months of the initial lesion, and continuously enlarged. The lesions continued to expand and the patient experienced severe pruritus that was refractory to topical glucocorticoid ointment and oral antihistamines prescribed by a dermatologist. She was then referred to our hospital for an evaluation. Physical examination revealed that the lesions were uniformly brown‐pigmented, moderately sclerotic plaques surrounded by pruritic reticular erythema (Fig. 1a–c). The lesions were distributed symmetrically on the upper extremities, upper back, abdomen and knees, and were sharply demarcated (Fig. 1d). The brown‐pigmented part of the lesion was obviously indurated, but not so hard as woody induration. The surface of the lesion was not atrophic. Sclerodactyly and nailfold haemorrhage were absent, but the dorsa of the fingers were slightly swollen. The patient denied having Raynaud’s phenomenon. She worked as a helper in a private hospital, and had never undergone cosmetic procedures, been exposed to organic solvents or taken nutritional supplements. She had been taking phenobarbital for 8 years due to an episode of epilepsy.
Famine Oedema in Prisoners of War
Authors: D. S. Stevenson
Journal: BMJ (1944)

manifest, and the count remained more or less constant at this level until after confinement.When she was last seen her condition was excellent.The blood findings were: R.B.C., 3,990,000 per c.mm.; Hb, 12.04 g.% (Sahli); W.B.Q., 8.650 per c.mm.; M.C.H., 30.2 yy.Case 4.-A male creole aged 22 had been sick for nine months with weakness, dyspnoea on exertion, and bleeding from the gums.When seen, pallor was marked, and there was some periodontal ulceration and sponginess of the gums, with secondary infection of the left wisdom tooth and oedema of the left cheek.The blood findings were: R.B.C., 1,890,000 per c.mm.; Hb, 8.26 g.% (Sahli); W.B.C., 5,600 per c.mm.; packed cells 27.4%; M.C.H., 43.7 yy; M.C.V., 144.9 c.,u; bleeding time, 4 min.;coagulation time, 6 min.Subtertian and benign tertian malaria parasites were found.Van den Bergh: 0.6 mg.bilirubin per 100 c.cm. Stools: anky'ostome ova +; urine: pus cells + +.Spleen just palpable.Treatment with yeast 3 oz.daily was begun, with quinine gr. 15 intramuscularly
Management of nocturnal enuresis
Authors: P. H. Y. Caldwell, A. V. Deshpande, A. V. Gontard
Journal: BMJ (2013)

#### Summary points

#### Sources and selection criteria

We searched Medline, Embase, and the Cochrane Database of Systematic Reviews using the search terms “enuresis” or “bedwetting” as keywords. Systematic reviews, meta-analyses, population based studies, randomised controlled trials, and studies published in the past five years were prioritised.

Nocturnal enuresis (enuresis or bedwetting) is the most common type of urinary incontinence in children. Depending on the definition, prevalence is 8-20% for 5 year olds, 1.5-10% for 10 year olds, and 0.5-2% for adults, with 2.6% of 7.5 year old children wetting on two or more nights a week.1 Prevalence seems to be similar worldwide. Here, we review current knowledge about the treatment of this common condition.

Nocturnal enuresis is intermittent involuntary voiding during sleep in the absence of physical disease in a child aged 5 years or more. A minimum of one episode a month for at least three months is required for the diagnosis to be made.2

A large epidemiological study showed that nocturnal enuresis is more common in males at all ages, and is more likely to persist in those with frequent wetting.3 Nocturnal enuresis is usually idiopathic and is commonly associated with daytime urinary incontinence (seen in 3.3% of 7.5 year olds in a large epidemiological study1), faecal incontinence, and chronic constipation. In …
712. Treatment of Human and Rat Hepatocellular Carcinomas by Long Term Expression of rAAV-Mediated Transfer of Human TERTC27 Polypeptide
Authors: Marie C. Lin, Samuel S. Ng, Yi Gao, ChingTung Lum, ZhenFan Yang, JunJian Huang, George K. Lau, SheungTat Fan, Hsiang-fu Kung
Journal: Molecular Therapy (2005)

The re-activation of human telomerase reverse transcriptase (hTERT) plays a major role in the carcinogenesis of hepatocellular carcinoma (HCC). In Hong Kong, hTERT is activated in approximately 85% of the HCC patients. We have previously demonstrated that constitutive expression of a 27 kDa C-terminal fragment of human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorgenicity of hTERT positive human cervical cancer Hela cells (Huang et al., Cancer Res., 2002). In this study, the therapeutic effect of hTERTC27 was further tested in vivo in different models harboring either human or rat HCC. A recombinant adeno-associated virus (rAAV) plasmid encoding hTERTC27 was constructed and high-purity rAAV-hTERTC27 vectors were prepared. We first showed that intratumoral injection of rAAV-hTERTC27 is highly efficient in inhibiting the growth of human HCC, Hep3B cells, transplanted subcutaneously in nude mice. The expression of hTERTC27 in the tumor was confirmed by Western blotting analysis. Histological studies indicated that injection of rAAV-hTERTC27 produced profound apoptosis and necrosis in the TERT positive Hep3B cells.
Foreign health workers look set to escape Libyan death sentence
Authors: Owen Dyer
Journal: BMJ (2007)

Death sentences pronounced by a Libyan court on five Bulgarian nurses and a Palestinian intern accused of deliberately infecting Libyan children with HIV looked to be on the point of being overturned as the BMJ went to press.

Relatives of the infected children agreed to drop calls for capital punishment in return for compensation of $1m (£0.5m, €0.7m) for each family, the Bulgarian television channel BTV said.

A hearing before Libya's Supreme Judicial Council concerning the fate of the foreign workers had been set for 16 July, but it has been postponed twice. The Libyan government gave …
The therapeutic promise of disrupting the PD-1/PD-L1 immune checkpoint in cancer: unleashing the CD8 T cell mediated anti-tumor activity results in significant, unprecedented clinical efficacy in various solid tumors
Authors: Emanuela Romano, Pedro Romero
Journal: Journal for ImmunoTherapy of Cancer (2015)

The role of immune checkpoints in modulating the magnitude as well as the functional profile of T cell responses is increasingly understood in molecular detail. Antibody-mediated blockade of co-inhibitory receptors has been shown to restore T cell function in both chronic viral infections and cancer. The latter has been successfully translated to new therapeutic options in the treatment of cancer. Indeed, monoclonal antibodies blocking either CTLA-4 or PD-1 have recently been approved for the treatment of metastatic melanoma in the United States, Europe and Japan. In this commentary, we summarize and put into perspective five letters recently published back to back in the November 27 (2014) issue of Nature reporting on different immunological and clinical aspects of blockade of the PD-1/PD-L1 pathway in tumor bearing hosts. Notably, treatment with anti-PD-L1 blocking antibody was shown result in profound clinical responses in patients with several solid tumor including bladder, lung and head and neck carcinomas among others. These five simultaneous publications highlight the tremendous therapeutic potential of targeting the PD-1/PD-L1 immune checkpoint and emphasize the need to identify appropriate biomarkers to guide their optimal clinical application.
Lipoxygenase products in inflammatory synovial fluids and other exudates.
Authors: P B Costello, A N Baer, F A Green
Journal: Annals of the Rheumatic Diseases (1992)

Forty six synovial fluid samples from 42 patients with inflammatory joint disease were analysed by reversed phase high performance liquid chromatography to determine 5-lipoxygenase products, specifically dihydroxyeicosatetraenoic acids (diHETEs). Twenty eight per cent of the fluids which were assayed had one or more products of 5-lipoxygenase activation. Seven fluids contained leukotriene B4 (0.1-28.1 ng/ml); three fluids had low concentrations of 20 carboxy/hydroxy-leukotriene B4 (0.01-0.05 ng/ml); three samples had leukotriene B4 isomers (1.5-2.4 ng/ml); and four fluids contained 5,15-diHETE (2.3-16.4 ng/ml). There was a poor correlation between synovial fluid white blood cell counts and evidence of 5-lipoxygenase activation. Several fluids contained unidentified compounds with spectra similar in shape to that of trienes, but the lambda max values of these unidentified compounds were different from those of known leukotrienes. A septic peritoneal exudate and a septic pleural fluid had concentrations of leukotriene B4 and leukotriene B4 isomers and metabolites in a range similar to those found in synovial fluids.
Rapid Molecular Cloning of Rearrangements of the IGHJ Locus Using Long-Distance Inverse Polymerase Chain Reaction
Authors: T.G. Willis, D.M. Jadayel, L.J.A. Coignet, M. Abdul-Rauf, J.G. Treleaven, D. Catovsky, M.J.S. Dyer
Journal: Blood (1997)
A Time Study of Medical Teaching Rounds
Authors: Henry E. Payson, Jack D. Barchas
Journal: New England Journal of Medicine (1965)

THIS is a report of observation and analysis of performance in medical rounds. Medical rounds are traditionally an essential disciplinary exercise in teaching hospitals. This study seeks to answer the following questions: what actually occurs during rounds with reference to how senior physicians spend their time; the self-estimate of senior physicians recording their own allocation of time during rounds; and how closely the actual behaviors are correlated with the self-estimates of time allotments. We believed that answers to these questions should be sought because rounds are often the most important formal teaching exercise of clinical discipline; the senior man present . . .
Abstract LB-260: Identification of DTYMK and CHEK1 as therapeutic targets in LKB1 mutant non-small cell lung cancer
Authors: Yan Liu, Glenn S. Cowley, Travis J. Cohoon, David E. Root, Wong Kwok-kin
Journal: Cancer Research (2012)

Abstract The LKB1 tumor suppressor encodes a key metabolic sensor that integrates cell growth and metabolism. LKB1 is mutationally inactivated in multiple adult malignancies, including &amp;gt;20% of lung cancers, often simultaneously with activating KRAS mutations. LKB1 mutations are an important predictor of poor outcome and resistance to current therapeutic approaches. We employed an integrative approach to define novel therapeutic targets in Lkb1 mutant lung cancers. Matched cell lines from genetically engineered mouse models of cancer driven by activated Kras alone or in combination with Lkb1 deletion, were employed in high-throughput RNAi, kinase inhibitor, and metabolite screens. These screens identified knockdown of either Dtymk (deoxythymidylate kinase) or Chek1 (checkpoint kinase 1) as synthetically lethal with Lkb1 deficiency in both mouse and human lung cancer cell lines, and revealed that Lkb1 inactivation conferred marked sensitivity to treatment with CHEK1 inhibitors. Lkb1 deficient cells had a distinct metabolic profile, characterized by striking decreases in multiple nucleotide metabolites. Knockdown of DTYMK inhibited dTTP biosynthesis and, consequently, DNA synthesis, and knockdown of CHEK1 caused accumulation of DNA damage. We hypothesize that Lkb1 loss enhances dependence on these enzymes due to broad defects in nucleotide metabolism. Our studies support the development of therapies target DTYMK and CHEK1 in LKB1 mutant non-small cell lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-260. doi:1538-7445.AM2012-LB-260
Developmental screening of preschool children.
Authors: J A McCluskie
Journal: BMJ (1977)

Developmental screening of preschool children SIR,-I was intrigued by the article by Dr D J G Bain on "Methods used by general practitioners in developmental screening of preschool children" (6 August, p 363) in its revelation of such free-for-all methodology."Examination forms," "visual charts," "alter- native screening forms"-you think of it, the examining doctors choose it.Why are they
Mottling score predicts survival in septic shock
Authors: H. Ait-Oufella, S. Lemoinne, P. Y. Boelle, A. Galbois, J. L. Baudel, J. Lemant, J. Joffre, D. Margetis, B. Guidet, E. Maury, G. Offenstadt
Journal: Intensive Care Medicine (2011)
UN agencies call for more integrated approach to food crisis in poor countries
Authors: B. Roehr
Journal: BMJ (2009)

The world’s two billion poorest people are continuously on the edge of a food and nutrition crisis, and the current economic recession has made the situation much worse, warned a meeting of United Nations agencies and financial institutions this week. 

The recent spike in food prices and lack of availability of food “are symptoms of a system that is seriously dysfunctional,” said David Nabarro, UN assistant secretary general, at the workshop organised by the US Institute of Medicine and held on 14-16 July in Washington, DC.

Dr Nabarro …
The promotion of human mesenchymal stem cell proliferation by superparamagnetic iron oxide nanoparticles
Authors: Dong-Ming Huang, Jong-Kai Hsiao, Ying-Chun Chen, Li-Ying Chien, Ming Yao, Yin-Kai Chen, Bor-Sheng Ko, Szu-Chun Hsu, Lin-Ai Tai, Hui-Ying Cheng, Shih-Wei Wang, Chung-Shi Yang, Yao-Chang Chen
Journal: Biomaterials (2009)
Identifying hearing impairment in infants and young children.
Authors: D A Curnock
Journal: BMJ (1993)

An important problem in serological screening is the tendency for false positive results to arise owing to "sticky serum" or "ccross reactivity."This problem with specificity can now be overcome by using such tests as the western blot or the polymerase chain reaction.In the study of Brennan and colleagues 2-5% of the 96720 blood donors initially were positive for HTLV-I; only 35 of those were positive on one of two enzyme linked immunosorbent assays (but not true positives) and only five were truly infected with HTLV-I.'Of these five, four were white women with sexual contact as a risk factor, and one a drug misuser.The authors argue that selective screening based solely on ethnic origins would not exclude HTLV-I infection.Addi- tionally, they discuss the risks of blood borne HTLV-I infection and developing diseases against the costs of screening and counselling, as well as the cost per infection prevented and diseases contracted.Screening does not seem to be cost effective in Britain at present.Nevertheless, the issues of what other countries are doing, consumer protection, and product liability make the decision to screen blood donors non-selectively extremely complex.The incidence of infection in Britain so far is too low and the incubation time too long to justify screening all blood samples.As far as product liability and consumer protection are concerned, achieving zero risk is impossible given the remote chance that a seronegative specimen may give a positive result on testing with the polymerase chain reaction and that testing every specimen in this way could be prohibitively expensive.Meanwhile, the situation should be kept under regular review.Trends in seroprevalence may be more important indications for action than absolute values.
New directions for cell-based therapies in acute liver failure
Authors: Preeti Viswanathan, Sanjeev Gupta
Journal: Journal of Hepatology (2012)

The mortality in acute liver failure (ALF) remains high despite superior contemporary management. Although orthotopic liver transplantation (OLT) is best for rescue in ALF, donor organ shortages and contraindications or irreversible neurological complications may restrict OLT. Therefore, alternative therapeutic approaches for ALF are necessary. These are typically aimed at managing complications, ameliorating inflammation, providing hepatic support, and inducing liver repair/regeneration. Whether cell therapy would offer such benefits is of interest for many reasons: cells from one donor could be used for several people; cryopreserved and banked cells could be administered rapidly; cells could be transplanted multiple times; provision of hepatic support from transplanted cells could "bridge" to OLT; reseeding of the liver with transplanted cells could promote tissue repair; secretion of appropriate factors from transplanted cells could aid liver regeneration, which might avoid OLT altogether; cell therapy is technically simple and is also "reversible" because the native liver need not be removed.
Mystery of the Blue Pigmentation
Authors: Andrew McD. Johnston, Aamir A. Memon
Journal: New England Journal of Medicine (1999)

To the Editor: In their article on mutations of the cystic fibrosis gene in patients with chronic pancreatitis, Sharer et al. (Sept.3 issue) 1 concluded that the frequency of carriers of the 5T allele was significantly higher in these patients than in the general population.However, we believe that this conclusion may be incorrect.The authors did not use for comparison the control group of 600 unrelated partners of persons with a family history of cystic fibrosis in the northwest of England. 2 Rather, they used the series studied by Kiesewetter et al., 3 which included persons from the United States, Northern Ireland, Italy, and Greece.The control group should represent the population from which the case patients were selected.Moreover, the carrier rate of 10.4 percent for the 5T allele found among 134 patients with chronic pancreatitis was compared with a 5 percent prevalence among 224 normal chromosomes (143 from the parents of patients with cystic fibrosis and 81 from the general population). 3 The comparison of the carrier prevalence rate with the allele prevalence rate is inappropriate because the former is approximately two times as high, since a person has two homologous chromosomes.Thus, their conclusion that the frequency of the 5T allele among patients with chronic pancreatitis is "twice as high as expected" is incorrect.To date, there is no evi-dence that the 5T allele confers susceptibility to chronic pancreatitis.
Myocardial contrast echocardiography and the transmural distribution of flow: A critical appraisal during myocardial ischemia not associated with infarction
Authors: Sanjiv Kaul, Ananda R. Jayaweera, William P. Glasheen, Flordeliza S. Villanueva, Howard P. Gutgesell, William D. Spotnitz
Journal: Journal of the American College of Cardiology (1992)
Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease
Authors: Sandro Rossetti, Vickie J. Kubly, Mark B. Consugar, Katharina Hopp, Sushmita Roy, Sharon W. Horsley, Dominique Chauveau, Lesley Rees, T. Martin Barratt, William G. van't Hoff, W. Patrick Niaudet, Vicente E. Torres, Peter C. Harris
Journal: Kidney International (2009)
Dr. Croftan's Iodin Starch Test for Adrenal Extract.
Authors: S. P. Kramer
Journal: JAMA (1903)

Cincinnati, Jan. 15, 1903. <h3>To the Editor:</h3> —In a recent number ofThe Journal(Jan. 10, 1903, p. 91) Dr. Alfred C. Croftan has published a series of tests said to be characteristic of adrenal tissue or extract, by means of which he proposes to differentiate adrenal tissue and hypernephromata. One of the most striking and constant of these tests is described as "The Power to Decolorize Iodin-Starch Solution." The test is made in the following manner: Equal portions of starch solution having been distributed in several test tubes, hypernephroma extract was added to one-half of them, and then one drop of an alcoholic iodin solution was added to each. Those tubes that contained no hypernephroma extract immediately turned blue and remained blue, whereas those tubes that contained hypernephroma extract turned blue for an instant only and became immediately decolorized. It seemed to the writer to be important that this