tbuckley/cabot-search huggingface dataset:
Abstract 156: Screening and characterization of inhibitors of G-protein coupled receptor kinase GRK6 as potential therapeutics for multiple myeloma
Authors: Carly Griffin, Ratheesh Subramanian, Hassan S. Zaidi, Richard Marcellus, Babu Joseph, Methvin Isaac, David Uehling, Chungyee Leung-Hagesteijn, Rodger Tiedemann, Rima Al-awar
Journal: Cancer Research (2012)

Abstract Multiple myeloma (MM) is one of the most common hematological malignancies, but current therapy options are limited to high-dose chemotherapy or high-risk stem-cell transplantation. It is clear that the development of more selective and less toxic treatments for MM is greatly needed. In a recent kinome-wide RNAi study by Tiedemann and colleagues (2010), the G-protein coupled receptor kinase-6 (GRK6) was identified as a critical kinase required for survival of MM cells. This study also suggests that MM cells, but not other cell types, are dependent on GRK6; and that gene silencing by shRNA or siRNA of GRK6, but not other GRKs, results in decreased survival. At present, the G-protein coupled receptor (GPCR) signaling mediated by GRK6 in MM cells is not well understood. Our current research aims to identify the important GPCRs phosphorylated by GRK6 and the signaling proteins/pathways implicated in survival of multiple myeloma cells. Through gene silencing techniques and expression of either the wild-type or kinase-dead form of GRK6 protein, we have determined that a functional GRK6 kinase domain is required for survival of MM cells. We have also demonstrated that the signaling pathway downstream of CXCR4 phosphorylation by GRK6 is defective in cells expressing the kinase-dead GRK6-mutant protein. This loss of signaling by the GRK6-mutant protein was observed for other GPCRs found to be important for survival of MM cells. These findings helped to validate that the kinase domain of GRK6 is a potential target for MM, and spurred the identification of small molecule kinase inhibitors of GRK6. Compounds with high potency in preliminary biochemical assays were screened against MM and non-MM cell lines to evaluate their activity and specificity in vivo. Small molecule inhibition of GRK6 kinase activity is a novel approach to the treatment of MM, as it specifically targets a protein found to be critical for survival of these cells through an unbiased RNAi study. Treatment options for patients with MM are limited and based on our preliminary findings small molecule inhibitors of GRK6 offer an alternative therapeutic approach to the treatment of MM. 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 156. doi:1538-7445.AM2012-156
Occurrence of hemophilia in the United States
Authors: J. Michael Soucie, Bruce Evatt, Debra Jackson
Journal: American Journal of Hematology (1998)

An active surveillance system was used to identify all residents with hemophilia in six U.S. states (Colorado, Georgia, Louisiana, Massachusetts, New York, and Oklahoma). A hemophilia case was defined as a person with physician-diagnosed hemophilia A or B and/or a measured baseline factor VIII or IX activity (FA) of 30% or less. Case-finding methods included patient reports from physicians, clinical laboratories, hospitals, and hemophilia treatment centers. Once identified, trained data abstractors collected clinical and outcome data retrospectively from medical records. Among cases identified in 1993-1995, 2,743 were residents of the six states in 1994, of whom 2,156 (79%) had hemophilia A. Of those with available FA measurements, 1,140 (43%) had severe (FA < 1%), 684 (26%) had moderate (FA 1%-5%), and 848 (31%) had mild (FA 6%-30%) disease. The mean and median age was 25.4 and 23 years, respectively. The age-adjusted prevalence of hemophilia in all six states in 1994 was 13.4 cases/100,000 males (10.5 for hemophilia A and 2.9 for B). The prevalence by race/ethnicity was 13.2 cases/100,000 among white, 11.0 among African American, and 11.5 among Hispanic males. Application of age-specific prevalence rates from the six surveillance states to the U.S. population resulted in an estimated national population of 13,320 cases of hemophilia A and 3,640 cases of hemophilia B. For the 10-year period 1982-1991, the average incidence of hemophilia A and B in the hemophilia surveillance system (HSS) states was estimated to be 1 in 5,032 live male births.
Pharmacological targeting of the thrombomodulin–activated protein C pathway mitigates radiation toxicity
Authors: Hartmut Geiger, Snehalata A Pawar, Edward J Kerschen, Kalpana J Nattamai, Irene Hernandez, Hai Po H Liang, Jose Á Fernández, Jose A Cancelas, Marnie A Ryan, Olga Kustikova, Axel Schambach, Qiang Fu, Junru Wang, Louis M Fink, Karl-Uwe Petersen, Daohong Zhou, John H Griffin, Christopher Baum, Hartmut Weiler, Martin Hauer-Jensen
Journal: Nature Medicine (2012)
Effects of sodium valproate in 100 children with special reference to weight.
Authors: J Egger, E M Brett
Journal: BMJ (1981)

Excessive weight gain occurred in a patient who was taking sodium valproate and phenytoin. The sodium valproate was therefore withdrawn but the rapid weight loss that ensued led to phenytoin intoxication. Hence a retrospective analysis was conducted of 100 children with epilepsy treated with sodium valproate. Fit control improved in 77 and was best in children with generalised epilepsy. None of the reported severe side effects, such as acute liver disease and pancreatitis, were encountered. Milder but troublesome side effects, however, occurred in 65 patients. The commonest was increased weight gain, which occurred in 44 cases. Others were transient gastrointestinal disturbances (20), lassitude (nine), transient hair loss (six), transient enuresis (seven), and aggressive behaviour (four).
Genetic polymorphisms of the HCR gene and a genomic segment in close proximity to HLA-C are associated with patients with psoriasis in Taiwan
Authors: Y.T. Chang, Y.M. Shiao, P.J. Chin, Y.L. Liu, F.C. Chou, S. Wu, Y.F. Lin, L.H. Li, M.W. Lin, H.N. Liu, S.F. Tsai
Journal: British Journal of Dermatology (2004)

Background Although psoriasis vulgaris (PV) is strongly associated with HLA-Cw*0602, it has been proposed that the association of Cw*0602 is due to linkage disequilibrium and that other nearby genes are involved in PV susceptibility. The α-helix coiled-coil rod homologue (HCR) gene, located 110 kb telomeric to the HLA-C locus, is presumed to be one of the PV candidate genes. Recently, a 10-kb genomic segment, centromeric to HLA-C, defined by two new single nucleotide polymorphisms (SNPs) n.7*A and n.9*C, was found to have a stronger association with psoriasis than the HCR gene. Until now, no study of the association of the HCR gene, SNPs n.7, and n.9 has been conducted on Chinese patients with psoriasis. Objectives We aimed to determine whether the genetic polymorphisms of the HCR gene, SNPs n.7*A, and n.9*C were associated with an increased risk of psoriasis in Chinese patients. Methods Using direct sequencing of the HCR gene and the genomic region containing SNPs n.7 and n.9, we investigated the HCR gene, SNPs n.7, and n.9 for disease association in 115 Chinese patients with psoriasis and 103 control subjects. The HCR SNPs were confirmed by denaturing high performance liquid chromatography. Genotyping for HLA-Cw*0602 was also carried out using sequence-based typing. Results We observed a different allelic distribution between patient and control groups at nucleotide positions 386, 404, 1802 and 2406 of the HCR gene, and SNPs n.7, and n.9. The associations were much stronger in early onset PV patients (for HCR-386*T and HCR-404*T, odds ratio = 5·63, Pc < 0·0001). The HLA-Cw*0602 also displayed a similar association with PV (odds ratio = 5·4, Pc < 0·0001). Moreover, SNP n.7*A, SNP n.9*C, Cw*0602, HCR-386*T, HCR-404*T and HCR-1802*T were in linkage disequilibrium with each other. Haplotype-based association analysis showed SNP n.7*A–SNP n.9*C–Cw*0602–HCR-386*T–HCR-404*T–HCR-1802*T–HCR-2406*G as a major susceptibility haplotype in this Chinese population (for early onset patients, odds ratio = 5·15, Pc < 0·0001). Conclusions Our results indicate that the HCR gene, SNP n.7*A, and SNP n.9*C as well as Cw*0602 are major susceptibility markers for psoriasis in Chinese patients.
Congenital Hypertrophic Pyloric Stenosis
Authors: A. A. H. Gailey
Journal: BMJ (1948)

Two cases of hypertrophic pyloric stenosis in the adult are reported.Both show an absence of the usual lifelong history of gastric discomfort.One had a remarkably thick muscular coat and pre- sented a palpable mass before operation.The view is expressed that mild degrees of the condition may be rela- tively common, and the suggestion made that if the difficul- ties of accurate diagnosis can be overcome some less drastic treatment than partial gastrectomy may be possible.
Lichenoid Eruptions Due to Methyldopa
Authors: C. J. Stevenson
Journal: British Journal of Dermatology (1971)

Journal Article Lichenoid Eruptions Due to Methyldopa Get access C. J. Stevenson C. J. Stevenson Department of Dermatology The Royal Victoria Infirmary Newcastle upon Tpie NEl 4LP Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 85, Issue 6, 1 December 1971, Page 600, https://doi.org/10.1111/j.1365-2133.1971.tb14097.x Published: 01 December 1971
Santorini's Duct – An Insignificant Variant from Normal or an Important Overflow Valve?
Authors: U. Mairose, D. Wurbs, M. Classen
Journal: Endoscopy (1978)

In a retrospective examination 250 consecutive pancreatograms obtained by ERCP were controlled on the existence of a D. Snatorini. Starting from the genetic development of the pancreatic ducts the question is investigated whether a second open pancreatic duct is responsible for a better drainage of the pancreas. Thus this duct may prevent hyperamylasemia and hyperlipasemia following ERCP. From an etiological point of view the elevation of these pancreatic enzymes is insufficiently understandable. If a D. Santorini is detectable the results demonstrate a reduction of the increased pancreatic enzymes in a statistically significant manner. A valve mechanism of the D. pancreaticus minor with volume or pressure reduction is postulated.
Pharmacogenic Disease in Psychiatry
Authors: P. Polonio
Journal: BMJ (1961)

Professor MCMICHAEL: It can be symptomless, dry, or haemorrhagic.Dr. STRADLING: Certainly when he first came to the Chest Clinic we did not think he had bronchiectasis; there were no physical signs to suggest it and we did not do any bronchograms, so that we have no positive evidence either to support or to refute your suggestion.I'm very sorry.Dr. SCADDING: There is some evidence in those x-rays, though, isn't there ?Some in the serial x-rays between the first one in 1950 (Fig. 3).Dr. STRADLING: That it developed subsequently ?Dr. SCADDING: Yes, between the first one in 1950 and the subsequent one (Fig. 4) there had been gross contraction of the base of the right lung.It seems inescapable that the bronchiectatic condition was associated with the contraction of the lung which occurred between those two x-rays.Professor MCMICHAEL: Yes, but that does not say that these lungs were utterly and completely anatomi-
CIGARETTE SMOKING IN RENOVASCULAR HYPERTENSION
Authors: JosephL. Lyon, KatharinaL. Schuman, ElectraD. Avlon, HerbertG. Langford, JohnP. Nicholson, SamL. Teichman, MichaelH. Alderman, T.A. Sos, T.G. Pickering, JohnH. Laragh
Journal: The Lancet (1984)
Notification of tuberculosis: how many cases are never reported?
Authors: C D Sheldon, K King, H Cock, P Wilkinson, N C Barnes
Journal: Thorax (1992)

Notification of tuberculosis is essential for local contact tracing and for assessing the national incidence of tuberculosis. The accuracy of notification figures is uncertain. This study examined the notification rates of all patients diagnosed as having tuberculosis at two hospitals in the East End of London over five years.In a retrospective survey of all patients aged 16 years or more presenting with tuberculosis to the London Chest Hospital or the Royal London Hospital from 1 January 1985 to 31 December 1989, cases of tuberculosis were identified from microbiology and histology records, statutory notifications, necropsy reports, coroners' records, hospital activity data, and death certificates. Clinical data were obtained from case notes and notification was determined from the local authority notification lists.Six hundred and nine adult patients with tuberculosis were identified. Notes were available for 580 cases (95%), of which 426 (73%) had been notified. The proportion of cases notified varied according to the specialty of the clinician in charge of the patient at diagnosis. Patients with a past history of tuberculosis and those who died within one year were less likely to have had their tuberculosis notified. Age, race, and lack of microbial or histological confirmation of diagnosis did not influence the proportion of cases notified. One hundred and eighty five patients had smear positive sputum, but 25 of these cases (14%) were not notified. Eighty five patients who had presented with pulmonary tuberculosis did not have their disease notified; 20 (24%) had smear positive sputum.Many cases of tuberculosis are not notified (27%). Fourteen per cent of all sputum smear positive cases of tuberculosis were not notified, and these patients are a considerable public health risk. The true incidence of tuberculosis in the area studied is at least one third higher than current notification figures suggest.
Perinatal death recording: time for a change?
Authors: M J Scott, J W Ritchie, B G McClure, M M Reid, H L Halliday
Journal: BMJ (1981)

The new perinatal death certificate proposed by the World Health Organisation was examined in relation to existing measures for recording perinatal death statistics and also with regard to new information gathered. Present procedures appear to underestimate the number of perinatal deaths by roughly 10%, though late registrations may lower this figure slightly. The use of a minimum birth weight as the criterion for inclusion in perinatal statistics removed much of the uncertainty associated with definitions of live birth and stillbirth. The new certificate led to duplication of some information already recorded through birth notification yet failed to provide information on some other factors generally considered relevant to perinatal mortality. The format proposed for recording cause of death provided a more logical presentation of events. Standardizing birth information recorded on all infants, modifying death certificates, and developing efficient record-linkage schemes would be more valuable than introducing the WHO certificate. Useful interpretation of the meaning of the characteristics of infants dying in the perinatal period awaits these timely changes.
Statistical methods for testing functional divergence after gene duplication
Authors: X. Gu
Journal: Molecular Biology and Evolution (1999)

Functional innovations after gene duplication may result in altered functional constraints between member gene clusters of a gene family. This type (type I) of functional divergence is measured by the coefficient of functional divergence (theta lambda), which can be interpreted as the decrease in rate correlation between gene clusters, or the probability that the evolutionary rate at a site is statistically independent between two gene clusters. A simple stochastic model has been developed for estimating theta lambda and testing its statistical significance. The current model includes the model of rate variation among sites as a special case when theta lambda = 0. Moreover, we have developed a site-specific profile based on the hidden Markov model to identify critical amino acid residues that are responsible for these functional differences between two gene clusters, which may have great potential in functional genomics.
Tendo Achillis pain: steroids and outcome.
Authors: M T Read, S G Motto
Journal: British Journal of Sports Medicine (1992)

A retrospective study is presented of 83 athletes with tendo Achillis pain (TAP) treated conservatively over a 12-year period from 1976 to 1988. Local steroid injections did not contribute to an earlier return to sport, though many individuals were improved symptomatically. Local steroids were not found to have a deleterious effect on outcome. Steroids were used most frequently in the chronic cases that presented late and had been treated previously: this group had most recurrences and surgical intervention. One case of Achilles rupture (3%) occurred in the group treated with steroids. Early presentation for treatment led to an earlier return to sport and avoidance of recurrences. Recurrences were most frequent in athletes with bilateral Achilles tendinopathy. The tendo Achillis lesion may range from peritendinitis through a mixed lesion of the tendon and paratenon, to complete rupture. The management depends upon accurate diagnosis, its chronicity and the age and aspirations of the patient. Steroids are safe to use and further prospective trials should note presentation time and disease staging accurately.
Helicobacter pylori and peptic ulcers: the present position.
Authors: S Moss, J Calam
Journal: Gut (1992)

Leading articleHelicobacter pylori and peptic ulcers: the present positionWe are currently at a curious point in the evolution of treat- ment for peptic ulcer.On one hand it has been discovered that eradication ofHelicobacterpylori offers an excellent solu- tion to the problem of duodenal ulcer relapse.On the other hand most clinicians still choose to treat ulcers with regimens that do not offer this benefit.This could be dismissed as 'natural conservatism' or 'healthy scepticism' but the issue seems to be more profound.A doctor wishing to accept that H pylori and its eradication are important is immediately confronted with unresolved problems.Firstly, we have come to expect rational explanations, but some information on H pylori seems confused and in particular there is no consensus on how it causes ulcers.Secondly, there is no general agreement on how H pylon should be eradicated.This review discusses some of these problems and how they may be resolved.
Use of anaesthesia. Implications of day-case surgery and anaesthesia.
Authors: T W Ogg
Journal: BMJ (1980)

Use of anaesthesiaImplications of day-case surgery and anaesthesia T W OGG In 1977 hospital day-case surgical procedures performed in England numbered 536 893, mainly in the specialties of urology, gynaecology, orthopaedics, and general surgery.Outpatient surgery was especially common in the larger regions-namely Mersey, W Midlands, North-west, and Trent.By definition day-case surgery is surgery performed on an outpatient basis with patients being admitted and discharged between 8.30 am and 5 pm.Ideally, surgery needing general anaesthesia should be undertaken during morning operating sessions.British doctors are aware of the long NHS surgical waiting lists and of the need to increase efficiency and make financial savings within the expensive hospital service.Indeed, the Department of Health's planning guidelines for 1977-8 emphasised the need for the development of more day-surgery facilities.In 1908 Nicoll operated successfully on 2392 children as outpatients in Glasgow.' Since then the work of several day-case units has been described.2-4The advantages and disadvantages
Don't leave the “un” off “consciousness”
Authors: Neal R. Swerdlow
Journal: Behavioral and Brain Sciences (1995)

Abstract Gray extrapolates from circuit models of psychopathology to propose neural substrates for the contents of consciousness. I raise three concerns: (1) knowledge of synaptic arrangements may be inadequate to fully support his model; (2) latent inhibition deficits in schizophrenia, a focus of this and related models, are complex and deserve replication; and (3) this conjecture omits discussion of the neuropsychological basis for the contents of the unconscious.
Adult‐onset asthma is associated with self‐reported mold or environmental tobacco smoke exposures in the home
Authors: J. Thorn, J. Brisman, K. Torén
Journal: Allergy (2001)

Background: In recent years, we have gained better knowledge about the influence of indoor environments on respiratory symptoms and asthma. The purpose of this study was to examine certain exposures in the home environment and the risk of adult‐onset asthma. Methods: A nested case‐referent study of adult‐onset asthma was performed in a random population sample ( n =15 813), aged 20–50 years. Cases for the study included subjects reporting “physician‐diagnosed” asthma ( n =174). The referents ( n =870) were randomly selected from the whole population sample. The case‐referent sample was investigated with a comprehensive mailed questionnaire about exposures in the home environment, asthma, respiratory symptoms, smoking habits, and atopy. Odds ratios (OR) with 95% confidence intervals (CI) were calculated while controlling for age, sex, smoking, and atopy. Results: Increased adjusted OR for asthma were associated with exposure to molds (OR 2.2, 95% CI 1.4–3.5), environmental tobacco smoke (OR 2.4, 95% CI 1.4–4.1), and the presence of a wood stove (OR 1.7, 95% CI 1.2–2.5). Conclusions: This population‐based case‐referent study indicates that self‐reported domestic exposures to molds or environmental tobacco smoke can be associated with adult‐onset asthma.
New Approaches to Treating B-Cell Cancers Induced by Epstein–Barr Virus
Authors: Vikas R. Dharnidharka, Thallachallour Mohanakumar
Journal: New England Journal of Medicine (2015)

Two preclinical studies show that boosting numbers of T cells or rendering T cells resistant to the immunosuppressant tacrolimus are potential approaches for the treatment of post-transplantation lymphoproliferative disease associated with EBV infection.
WHO needs more money to deliver better health care to poor people
Authors: Owen Dyer
Journal: BMJ (2005)

The World Health Organization is under-resourced, lacks direction, and is run by staff who are jaded and poorly managed, says a highly critical report from an independent health charity. To deliver the basic health needs lacking in the developing world WHO needs to re-examine its structure and policies and call for better funding, it says.

The report is produced by the charity Medact and the People's Health Movement, the umbrella group that organised the first People's Health Assembly in Savar, Bangladesh, in December 2000.

It says that resources devoted to WHO's international programmes are far smaller than most people believe. The global …
Victor Henry Wheble
Authors: A. Wheble
Journal: BMJ (2010)

Victor won a LCC (London County Council) scholarship to Dulwich College, 1931-8. In July 1934, rising 15, he passed the school certificate with credits in English, maths, and physics. He stayed at school for another four years, where he reorganised the school museum and library. He was a prefect and head of science side. He played cricket for the third XI and was president of the Science and Photographic Society. He developed a lifelong love of cricket.

He went up to Brasenose College, Oxford, as a Hulme exhibitioner, 1938-41. He played hockey, cricket, and squash for the college. Parts 1 and 2 of his medical degree were graded 1st class in 1941, his BA formally being awarded on 7 June 1941. Victor loved his time at Oxford and would have stayed on except he needed to qualify urgently because the second world war was in deadly full swing. Victor proceeded to King’s College Hospital, London, to finish his medical training, where he excelled and won a pathology exhibition and the senior scholarship awarded to the best student in the year.

The war was at its height, and no one knew how long it would last. During the day the hospital had to continue with business as usual. He graduated in 1944. Many evenings there would be up to 80 critically injured people from the Blitz. As one of the senior resident doctors he had to carry out triage. Recently he related with sorrow the case of a man who insisted that Victor attend to his daughter first …