tbuckley/cabot-search huggingface dataset:
Smoking, rheumatoid factor status and responses to rituximab
Authors: Abdul Khan, David Lloyd Scott, Mike Batley
Journal: Annals of the Rheumatic Diseases (2012)

As many active rheumatoid arthritis (RA) patients do not fully respond to biological therapies, there is growing interest in response predictors. Rheumatoid factor (RF) status predicts responses to rituximab; seropositive patients have higher response rates.1,–,5 Smoking status predicts responses to tumour necrosis factor (TNF) inhibitors; non-smokers have higher response rates.6,–,9

We evaluated whether smoking and autoantibody status interact in predicting responses to rituximab in active RA patients treated in routine practice settings. We used National Institute for Health and Clinical Excellence response criteria of falls in Disease Activity Scores for 28 joints (DAS28) of ≥1.2 after 6 months treatment in patients with initial DAS28 scores >5.1.

We studied 150 sequential RA patients receiving rituximab in southeast London and Kent. They comprised 109 women and 41 men, mean age …
Effects of Catecholamines and Renal Nerve Stimulation on Renin Release in the Nonfilterlng Kidney
Authors: J. Alan Johnson, James O. Davis, Robert T. Witty
Journal: Circulation Research (1971)

The mechanisms whereby catecholamines and renal nerve stimulation increase renin secretion were studied in dogs with nonfiltering kidneys. In six dogs, epinephrine was infused into the renal artery at a rate that decreased renal blood flow to half of the control value. Papaverine was then infused into the renal artery to block the decrease in renal blood flow produced by the catecholamine, and the epinephrine infusion was resumed while the papaverine infusion was continued. In this experiment, renin release increased during infusion of epinephrine alone, but no change occurred with epinephrine during papaverine infusion. The protocol for the experiment on six other dogs was similar except that the infused catecholamine was norepinephrine. In this experiment, norepinephrine increased renin release both prior to and during papaverine infusion. In seven dogs, the effect of electrical stimulation of the renal nerves on renin secretion was studied both before and during the infusion of papaverine into the renal artery; renin release increased strikingly both before and during papaverine infusion. It is suggested that epinephrine increased renin secretion in the nonfiltering kidney by an action on the renal arterioles. In contrast, norepinephrine and renal nerve stimulation apparently increased renin secretion in the nonfiltering kidney by a direct effect on the juxtaglomerular cells. These data provide evidence for specific mechanisms of action of epinephrine, norepinephrine, and the renal nerves in renin release.
Trauma and Cancer: Pathology for the Lawyer
Authors: Richard C. Froede
Journal: JAMA (1976)

This monograph attempts to bring some order to the chaos that exists in the literature, in testimony, and in thinking concerning the causal relationship between trauma and cancer. The author seeks to relate medical knowledge to the legal process in order to clarify variation of opinion that might be presented in a court of law. Written primarily for the legal profession, much of the text is a very basic discussion of the reaction of the body to injury, the history of cancer, terminology, and the origin and behavior of tumors. To the physician, this portion of the book would appear oversimplified and cursory, but it does provide the attorney with some background for the understanding of cancer. The relevant material is presented as case reports, with sections on trauma and inflammation, scars and cancer, and trauma as a causative or aggravating agent in cancer. A physician who becomes involved as
SIMPLE METHOD OF TEMPORARILY SPLINTING FRACTURE OF LONG BONE
Authors: D. Stoddard Dooman
Journal: JAMA (1924)

An emergency measure for temporarily splinting fractures of shafts of the long bones, which I am unable to find mentioned in surgical textbooks, is as follows: That part of the leg, arm or forearm which is fractured is encircled with one of the large weekly periodicals and tightly secured with a bandage. This seems to immobilize the fractured bone satisfactorily until such time as the patient can receive proper treatment.
176. An Inhibitor of Fumarylacetoacetate Hydrolase (Fah) for Selection of Transplanted Hepatocytes and Gene Correction In Vivo
Authors: Karsten Wursthorn, John F. Witte, R.L. Bateman, Milton Finegold, Ronald W. McClard, Markus Grompe
Journal: Molecular Therapy (2006)

Mice deficient in the tyrosine catabolic enzyme Fah are an excellent model for liver repopulation by selection. Fah positive cells from several different origins can engraft and correct the phenotype of a Fah-mutant liver. Non-cell based gene therapy leading to the in situ correction of the Fah-deficiency also works and repopulation levels of >90% are routinely achieved. Thus, hepatic Fah deficiency provides a powerful in vivo selection environment for cells genetically resistant to the enzyme deficiency. In order to mimic the same selective pressure in animals not genetically deficient in Fah, we developed a small molecule inhibitor of Fah. 4-[(2-carboxyethyl)- hydroxyphosphinyl]-3-oxobutyrate (CEHPOBA) has a nanomolar Ki for Fah and was injected intraperitoneally into C57/BL6 mice at a concentration of 1μmoles per gram body weight. In a first round of experiments, the duration of Fah inhibition in vivo was tested. We found that a once-daily injection resulted in a lasting enzyme repression. Next, we tested if transplanted hepatocytes could be selected under continuous CEHPOBA administration. As shown previously, hepatocytes mutant for the homogentisic acid dioxygenase (Hgd) an enzyme upstream of Fah in tyrosine catabolism are able to repopulate the livers of mice with Fah-deficiency. We therefore transplanted 500,000 sex-mismatched Hgd-mutant hepatocytes into Fah+ C57/BL6 mice and concomitantly started CEHPOBA treatment. Treated animals appeared healthy and displayed no major side-effects. After 4 weeks of daily CEHPOBA injection, the livers were harvested and analyzed by semi-quantitative PCR and histology for the presence of Y-chromosome. 1–10% of total hepatocytes were Y-chromosome positive. Transplanted, Y-chromosome positive hepatocytes displaying Fah wild type formed nodules proving clonal expansion and ongoing selection of the genetically favored hepatocytes. Our results show that a significant selection of genetically resistant hepatocytes can be achieved by CEHPOBA administration in vivo. This proof-of-principle opens the door to a whole new field of experimental and therapeutic options for cell transplantation and gene correction of liver diseases in vivo. CEHPOBA resistance occurs in cells lacking enzymes upstream of Fah in tyrosine metabolism and could therefore be achieved by shRNAs targeting these genes. This strategy is currently under investigation.
PULMONARY TUBERCULOSIS AS AN OBSTETRICAL COMPLICATION.
Authors: CHARLES SUMNER BACON
Journal: JAMA (1905)

Probably from 1 to 1.5 per cent. of all pregnant women have tuberculosis in such degree that it can be detected if careful examination is made. Freund found about 12 cases in 1,000. Of these patients, nearly half were in a serious condition. The fact that only about 50 per cent. of the cases discovered were comparatively mild suggests the possibility that a larger number of mild cases could have been discovered if a stricter examination had been made. We have not a sufficiently large statistic from other clinics to justify the statement above made concerning the frequency of the disease, but it is probably true because the ratio given corresponds to the frequency ratio of tuberculosis among adults between 15 and 45 years. This ratio is obtained from the consumption mortality rate and the duration of the disease. According to the United States census of 1900, there are 252
Abstract 280: Genetics and functions of Kaposi's sarcoma-associated herpesvirus (KSHV) glycoproteins in virion egress, infectivity and tumorigenesis
Authors: Oswald D'Auvergne, Ramesh Subramanian
Journal: Cancer Research (2012)

Abstract Kaposi's sarcoma-associated herpes virus (KSHV), or human herpes virus 8, is a lymphotropic oncogenic virus that has been implicated in the pathogenesis of Kaposi's sarcoma; body cavity-based B-cell lymphoma (BCBL), or primary lymphoma; and some forms of Multicentric Castleman's disease. We have developed a conditional silencing system for partial inhibition of KSHV viral glycoprotein synthesized genes that are not susceptible to siRNA inhibition. We have successfully used this system to demonstrate that KHSV glycoprotein B (gB) is necessary for virion egress from BCBL-1 cells and virus infectivity (Subramanian, D'Auvergne, et al. J. Virol. 2008, 82:7144-54). To investigate the potential role of gB in tumorigenesis, BCBL-1 cells were transiently transfected with anti-gB siRNAs and codon optimized gB were mixed with matrigel and injected subcutaneously in nude mice. Direct measurement of tumors revealed that BCBL-1 cells transfected with anti-gB siRNAs produced tumors significantly smaller than mock-transfected BCBL-1 cells. Co-transfection of codon optimized gB appeared to abrogate the inhibition of tumor formation by siRNAs. These results show that gB is important for infectivity, virion egress and pleural effusion lymphoma (PEL) formation in mice. 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 280. doi:1538-7445.AM2012-280
Use of personal medical records for research purposes
Authors: N. Wald, M. Law, T. Meade, G. Miller, E. Alberman, J. Dickinson
Journal: BMJ (1994)

The established practice of doctors using medical records for research purposes is threatened by the recent proposed guidelines from the Department of Health, the BMA, and the European Commission. The European Commission has proposed that explicit consent should be obtained from each patient before his or her medical records can be used; the proposals from the Department of Health and the BMA would require all research that needs access to personal medical records to be submitted to an ethics committee. We believe that these proposals would seriously impair an entire category of research and suggest therefore that another set of guidelines, proposed by a Royal College of Physicians' working group, should be used to modify the proposals. The guidelines of the working group encourage the use of medical records for research and ensure that such use can be made in a confidential manner without causing harm.
Points from Letters: Prescription Charge Anomalies
Authors: C. Lipp
Journal: BMJ (1973)

In 1970 340 of strains were resistant to tetracycline, in 1971 46%, in 1972 54%, and in 1973 to date 35°%.It would seem there- fore that in this area, at least, there has been no fall in the level of tetracycline-resistant Strep.pyogenes over the past four years.The majority of strains isolated continue to come from throat swabs, though many also come from skin sepsis and abscesses.Group B haemolytic streptococci show an even higher prevalence of tetracycline resistance- 580% of 74 strains isolated so far this year (mainly from vaginal swabs) were resistant to this drug.Whether the difference between Dr. Robertson's findings and mine is due to differences in the usage of tetracyclines in the two areas is something on which I cannot comment, but our results illustrate how widely divergent antibiotic sensitivity patterns may 'be observed in different areas of the couniry.-Iam, etc.,
A proximal activator of transcription in epithelial-mesenchymal transition
Authors: Christo D. Venkov, Andrew J. Link, Jennifer L. Jennings, David Plieth, Tsutomu Inoue, Kojiro Nagai, Carol Xu, Yoana N. Dimitrova, Frank J. Rauscher, Eric G. Neilson
Journal: Journal of Clinical Investigation (2007)

Epithelial-mesenchymal transition (EMT) is an important mechanism for phenotypic conversion in normal development and disease states such as tissue fibrosis and metastasis. While this conversion of epithelia is under tight transcriptional control, few of the key transcriptional proteins are known. Fibroblasts produced by EMT express a gene encoding fibroblast-specific protein 1 (FSP1), which is regulated by a proximal cis-acting promoter element called fibroblast transcription site–1 (FTS-1). In mass spectrometry, chromatin immunoprecipitation, and siRNA studies, we used FTS-1 as a unique probe for mediators of EMT and identified a complex of 2 proteins, CArG box–binding factor–A (CBF-A) and KRAB-associated protein 1 (KAP-1), that bind this site. Epithelial cells engineered to conditionally express recombinant CBF-A (rCBF-A) activate the transcription of FSP1 and undergo EMT. The FTS-1 response element also exists in the promoters modulating a broader EMT transcriptome, including Twist, and Snail, as well as E-cadherin, β-catenin, ZO 1, vimentin, α1(I) collagen, and α–smooth muscle actin, and the induction of rCBF-A appropriately alters their expression as well. We believe formation of the CBF-A/KAP-1/FTS-1 complex is sufficient for the induction of FSP1 and a novel proximal activator of EMT.
Abstract B30: Exogenous miR-128 Enforced HNSCC Inhibits Proliferation
Authors: Belinda Hauser, Yubin Hao, Joseph Califano, Xinbin Gu
Journal: Cancer Research (2012)

Abstract Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with complex molecular abnormalities. There are more than 65,000 Americans diagnosed with head and neck cancer and 25,000 die from this disease. microRNAs are 22~nucleotide-long endogenously expressed, highly conserved noncoding RNAs with important regulatory functions in proliferation, apoptosis, and metastasis. miR-128 a brain-enriched microRNA most commonly in gliomas that have shown to function as a tumor suppressor which decreases cell proliferation and cell invasiveness in prostate cancer. miR-128 has been shown to target BMI-1 in squamous cell carcinoma; however we believe miR-128 functions by targeting multiple targets in HNSCC. Methods: We established HNSCC cell lines that stably expressed individual members of the miR-128 using a lentiviral delivery system. The levels of miR-128 and their targeted proteins were analyzed by qRT-PCR and Western blot. miR-128 affinity was elucidated by MTT, colony formation, flow cytometry, and a tumor xenograft model. Results: Enforced transfection of miR-128 in HNSCC (JHU-22) expression was stable in vitro and in vivo. We identified five specific targets of miR-128 (BMI-1, BAG2, BAX, H3f3b, and Paip2). BMI-1 and H3f3b were shown to be a more dominant targeted of miR-128. Overexpression of miR-128, lead to the down regulation of these targets including decrease cell viability (30%), decrease of proliferation (55%), and significantly reduced solid tumor formation in tumor xenografts models. Conclusions: miR-128 exhibits anti-proliferative effects and phenotypic alteration in HNSCC by targeting multiple predicted conserved targets activity function in apoptosis, cell cycle, transcription, and translation. Therefore, screening for differentially expressed targets of miR-128 help elucidate the possible mechanisms underlining the function of miR-128.Our results indicate that miR-128 has the potential to serve as a therapeutic approach. Citation Format: Belinda Hauser, Yubin Hao, Joseph Califano, Xinbin Gu. Exogenous miR-128 Enforced HNSCC Inhibits Proliferation [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr B30.
Subliminal Fas stimulation increases the hepatotoxicity of acetaminophen and bromobenzene in mice
Authors: Marina Tinel, Alain Berson, Nathalie Vadrot, Véronique Descatoire, Alain Grodet, Gérard Feldmann, Jean Paul Thénot, Dominique Pessayre
Journal: Hepatology (2004)

The hepatotoxicity of several drugs is increased by mild viral infections. During such infections, death receptor ligands are expressed at low levels, and most parenchymal cells survive. We tested the hypothesis that subliminal death receptor stimulation may aggravate the hepatotoxicity of drugs, which are transformed by cytochrome P-450 cytochrome P-450 into glutathione-depleting reactive metabolites. Twenty-four-hour-fasted mice were pretreated with a subtoxic dose of the agonistic Jo2 anti-Fas antibody (1 μg per mouse) 3 hours before acetaminophen (500 mg/kg) or 1 hour before bromobenzene (400 mg/kg) administration. Administration of Jo2 alone increased hepatic inducible nitric oxide synthase nitric oxide synthase but did not modify serum alanine aminotransferase (ALT), hepatic adenosine triphosphate (ATP), glutathione (GSH), cytochrome P-450, cytosolic cytochrome c , caspase-3 activity or hepatic morphology. However, pretreating mice with Jo2 further decreased both hepatic GSH and ATP by 40% 4 hours after acetaminophen administration, and further increased serum ALT and the area of centrilobular necrosis at 24 hours. In mice pretreated with the Jo2 antibody before bromobenzene administration, hepatic GSH 4 hours after bromobenzene administration was 51% lower than in mice treated with bromobenzene alone, and serum ALT activity at 24 hours was 47-fold higher. In conclusion, administration of a subtoxic dose of an agonistic anti-Fas antibody before acetaminophen or bromobenzene increases metabolite-mediated GSH depletion and hepatotoxicity. Subliminal death receptor stimulation may be one mechanism whereby mild viral infections can increase drug-induced toxicity. (Hepatology 2004;39:655-666.)
Maternal serum alpha-fetoprotein in relation to zygosity.
Authors: N J Wald, H S Cuckle, S Peck, G M Stirrat, A C Turnbull
Journal: BMJ (1979)

The infusions were all of commonly used clear fluids and blood and there was no significant difference between the two groups.The added drugs were also evenly distributed.There were eight (17 %) cases of thrombophlebitis in the treatment group and 15 (31 %) among controls (P = 005).Patients in the treatment group took 40 % longer to develop thrombophlebitis than the controls: 66-4 hours compared with 47-4 hours.The average duration of the infusions in the treatment group (54-7± 14-1 hours) was longer than in the control group (46-7 ± 13-5 hours), but this reflected the greater number and earlier onset of cases of thrombophlebitis in the control group.When positive cases were excluded the averages were closer (controls 46-3 hours, treatment group 52-1 hours).There were no infective complications.
Evaluation of a Rapid Bedside Assay for Detection of Serum Cardiac Troponin T
Authors: Elliott M. Antman
Journal: JAMA (1995)

To evaluate a rapid, qualitative, bedside immunoassay for cardiac-specific troponin T (cTnT) using a handheld device containing monoclonal antibodies.Comparison of rapid cTnT assay with clinical standard for diagnosis of myocardial infarction (MI).Tertiary care university medical center.A cohort of 100 patients admitted for evaluation of chest pain who had sufficient blood samples at presentation for measurement of creatine kinase, creatine kinase MB fraction, and rapid cTnT as well as adequate clinical data to establish the diagnosis of MI.None; treating physicians were blinded to rapid cTnT results.Sensitivity and specificity of rapid cTnT assay for MI; likelihood ratios of positive and negative rapid cTnT assay results; relative risk (RR) for serious cardiac events with positive rapid cTnT assay result on admission.Sensitivity of the rapid cTnT assay increased from 33% within 2 hours from the onset of chest pain to 86% after 8 hours (P < .001); specificity ranged from 86% to 100% during the same time intervals. The odds of an MI increased sixfold with a positive assay result within 2 hours of chest pain and decreased sixfold with a negative assay result after 8 hours. The RR for experiencing death or nonfatal MI was 6.8 for patients presenting with a positive rapid cTnT assay.The rapid cTnT assay is a simple, efficient test that for the first time provides clinicians with a useful laboratory tool for point-of-care evaluation of patients with chest pain.
82 THE TNF-alpha −238 G-ALLELE PREDISPOSES TO SEVERE BACTERIAL INFECTION IN PATIENTS WITH END-STAGE LIVER DISEASE ENLISTED FOR LIVER TRANSPLANTATION
Authors: R. Bartáková, E. de Mare-Bredemeijer, S. Fraňková, D. Roelen, T. Visseren, P. Trunečka, J. Špičák, H. Metselaar, M. Jirsa, J. Kwekkeboom, J. Sperl
Journal: Journal of Hepatology (2013)
Geoffrey Norman Lumb
Authors: P. O'Boyle
Journal: BMJ (2003)

Former consultant urologist Taunton, Somerset (b Crewkerne 1925; q St Thomas's Hospital, London, 1948), died from complications of prostate cancer on 25 April 2003.​2003.




Figure 1




Geoffrey became consultant surgeon in Taunton in 1965. He resolved to create a department of urology, which was established in 1979, and Taunton became the first district general hospital training department in the south west. Under his guidance research programmes flourished and Taunton pioneered video endoscopy and laser surgery. Geoffrey cowrote a textbook on surgical diathermy. He was also an enthusiastic proponent of transrectal ultrasound examination of the prostate, which was at an early stage of development. Geoffrey had many interests, including model railway engineering. He leaves a wife, Alison, and three children.
Myocyte Nitric Oxide Synthase 2 Contributes to Blunted β-Adrenergic Response in Failing Human Hearts by Decreasing Ca <sup>2+</sup> Transients
Authors: Mark T. Ziolo, Lars S. Maier, Valentino Piacentino, Julie Bossuyt, Steven R. Houser, Donald M. Bers
Journal: Circulation (2004)

Background— Human heart failure (HF) usually exhibits blunted response to β-adrenergic receptor (AR) stimulation. Here, we examined whether expression of nitric oxide synthase-2 (NOS2, or inducible NOS) contributes to this loss of inotropic reserve in human HF. Methods and Results— Failing human hearts were obtained at transplantation. Contraction and [Ca 2+ ] i measurements were performed in isolated cardiac myocytes and trabeculae. In HF myocytes and muscle, isoproterenol (ISO), a β-AR agonist, led to small inotropic and lusitropic responses. Specific inhibition of NOS2 by aminoguanidine (AG) or L-NIL dramatically increased the ISO-induced inotropy and lusitropy, such that the ISO+AG response in HF approached that seen with ISO alone in nonfailing human myocytes or muscles. Ca 2+ transient data directly paralleled these results, indicating that altered cellular Ca 2+ handling is responsible. In nonfailing human hearts, NOS2 inhibition had no effects. In addition, NOS2 inhibition also had no effect in 30% of failing hearts, but in these myocytes and muscles, the ISO response alone was similar to that of nonfailing hearts. In line with these functional findings, NOS2 protein expression measured by Western blotting was induced in HF when AG/L-NIL had a functional effect but not when AG/L-NIL had no effect on contractility and Ca 2+ transients. Conclusions— NOS2 expression strongly limited ISO-induced increases in contraction, twitch Δ[Ca 2+ ] i , and lusitropy in trabeculae and isolated myocytes from failing human hearts. Thus, the β-AR hyporesponsiveness in human HF is mediated in large part by NO (or related congeners) produced within cardiac myocytes via NOS2.