tbuckley/cabot-search huggingface dataset:
Preclinical Development of a Bifunctional Cancer Cell Homing, PKCε Inhibitory Peptide for the Treatment of Head and Neck Cancer
Authors: Liwei Bao, Michael A. Gorin, Manchao Zhang, Alejandra C. Ventura, William C. Pomerantz, Sofia D. Merajver, Theodoros N. Teknos, Anna K. Mapp, Quintin Pan
Journal: Cancer Research (2009)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide, comprising approximately 50% of all malignancies in some developing nations. Our recent work identified protein kinase Cepsilon (PKCepsilon) as a critical and causative player in establishing an aggressive phenotype in HNSCC. In this study, we investigated the specificity and efficacy of HN1-PKCepsilon, a novel bifunctional cancer cell homing, PKCepsilon inhibitory peptide, as a treatment for HNSCC. HN1-PKCepsilon peptide was designed by merging two separate technologies and synthesized as a capped peptide with two functional modules, HN1 (cancer cell homing) and PKCepsilon (specific PKCepsilon inhibitory), connected by a novel linker module. HN1-PKCepsilon preferentially internalized into UMSCC1 and UMSCC36 cells, two HNSCC cell lines, in comparison with oral epithelial cells: 82.1% positive for UMSCC1 and 86.5% positive for UMSCC36 compared with 1.2% positive for oral epithelial cells. In addition, HN1-PKCepsilon penetrated HNSCC cells in a dose- and time-dependent manner. Consistent with these in vitro observations, systemic injection of HN1-PKCepsilon resulted in selective delivery of HN1-PKCepsilon into UMSCC1 xenografts in nude mice. HN1-PKCepsilon blocked the translocation of active PKCepsilon in UMSCC1 cells, confirming HN1-PKCepsilon as a PKCepsilon inhibitor. HN1-PKCepsilon inhibited cell invasion by 72 +/- 2% (P < 0.001, n = 12) and cell motility by 56 +/- 2% (P < 0.001, n = 5) in UMSCC1 cells. Moreover, in vivo bioluminescence imaging showed that HN1-PKCepsilon significantly (83 +/- 1% inhibition; P < 0.02) retards the growth of UMSCC1 xenografts in nude mice. Our work indicates that the bifunctional HN1-PKCepsilon inhibitory peptide represents a promising novel therapeutic strategy for HNSCC.
Combination Therapy with Multiple Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: A Preventive Strategy
Authors: Theodore Pincus, James R. O'Dell, Joel M. Kremer
Journal: Annals of Internal Medicine (1999)

The traditional "pyramid" or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti-inflammatory drug for months to years while seeking to avoid use of second-line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a "preventive" strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used "anchor drug" in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.
The Cardiomyopathies—Current Perspectives
Authors: JOSEPH K. PERLOFF
Journal: Circulation (1971)

This paper is designed to provide a contemporary overview of primary myocardial disease. The cardiomyopathies are dealt with in the light of both pathophysiologic and etiologic classifications. A relatively simple diagnostic approach is based upon these classifications together with the clinical manifestations of the cardiomyopathies. The essential principles of the natural history are summarized, and treatment is dealt with in terms of specific curatives, general pharmacologic measures, and management of factors that modify, aggravate, or contribute to the development of primary myocardial disease.
Abstract 2876: 3,3’-Diindolylmethane inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate model
Authors: Han Jin Cho, So Young Park, Eun Ji Kim, Jung Han Yoon Park
Journal: Cancer Research (2010)

Abstract 3,3’-Diindolymethane (DIM) is a major in vivo derivative of indole-3-carbinol, which is present in cruciferous vegetables and has been reported to evidence anti-carcinogenic properties. In the present study, we attempted to determine whether DIM inhibits the development of prostate cancer using the transgenic adenocarcinoma mouse prostate (TRAMP) model. DIM feeding inhibited prostate carcinogenesis in TRAMP mice, reduced the number of cells expressing the SV40 large tumor antigen and proliferating cell nuclear antigen, and increased the number of terminal dUTP nick-end labeling (TUNEL)-positive cells in the dorsolateral lobes of the prostate. Additionally, DIM feeding reduced the expression of cyclin A, cyclin-dependent kinase (CDK)2, and CDK4, and increased Bax expression. To assess the mechanisms by which DIM induces apoptosis, LNCaP and DU145 human prostate cancer cells were cultured with various concentrations (0 – 30 μmol/L) of DIM. DIM induced a substantial reduction in the numbers of viable cells and induced apoptosis in LNCaP and DU145 cells. DIM increased the cleavage of caspase-9, −7, −3, and poly (ADP-ribose) polymerase (PARP). DIM increased mitochondrial membrane permeability and the translocation of cytochrome c and Smac/Diablo from the mitochondria. Additionally, DIM induced increases in the levels of cleaved caspase-8, truncated Bid, Fas, and Fas ligand, and the caspase-8 inhibitor z-IETD-FMK was shown to mitigate DIM-induced apoptosis and the cleavage of caspase-3, PARP, and Bid. These results indicate that DIM inhibits prostate carcinogenesis via induction of apoptosis and inhibition of cell cycle progression. DIM induces apoptosis in prostate cancer cells via the mitochondria- and death receptor-mediated pathways. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2876.
Sexual health is another commissioning crisis
Authors: J. Clarke, E. Carlin
Journal: BMJ (2015)

We were concerned to read the investigation on NHS contracting and the threats to complex service provision and training reported in ophthalmology and dermatology.1 2 A crucial service to the public to detect, treat, and prevent HIV and other sexually transmitted infections (STIs) is also in peril.

In April 2013, English local authorities became responsible for commissioning services for sexual health, HIV …
Erythropoietin and ventricular remodelling: a VEGF-dependent neovascularity
Authors: T. Hamid, S. D. Prabhu
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure’ by B.D. Westenbrink et al. , pp. 30–39, this issue. 

To uncover novel therapeutics for heart failure (HF), attention has focussed on the biological factors that underlie the transition from an initially adaptive hypertrophic response to a maladaptive state that promotes progressive cardiac dysfunction. The cardiac microvasculature is an important factor in this regard inasmuch as insufficient capillary growth is thought to be an important contributor to progressive dysfunction and remodelling in HF.1 Unlike the increased capillary density seen in conditions of physiological cardiac hypertrophy,2 reduced microvascular density and fewer capillaries are commonly observed in failing hearts.1,3–6 Microvascular rarefaction in pathological hypertrophy imparts many untoward effects, including myocardial ischaemia due to deficient oxygen supply, inefficient cardiac metabolism, myocyte loss, inflammation, fibrosis, and contractile dysfunction.1,3–6 Changes in myocardial capillary density during myocardial hypertrophy have been linked to the expression of angiogenic factors such as vascular endothelial growth factor (VEGF).6 In murine models, pressure overload induces the expression of VEGF and angiopoietin 2 during the adaptive phase of hypertrophy, whereas blockade of VEGF signalling decreases myocardial neovascularization and accelerates the transition to failure.6 Hence, restoration of the cardiac microvasculature theoretically represents a viable strategy to improve cardiac function in HF.

Erythropoietin (EPO) is a growth factor that promotes the differentiation and proliferation …
Scientists produce new tool for studying brain development
Authors: Roger Dobson
Journal: BMJ (2006)

A new database on brain growth is about to become available that will improve research and diagnosis.

The resource, which is based on magnetic resonance imaging (MRI) scans of the developing brains of 500 healthy US children aged 7 days to 18 years, is expected to be available to clinicians and researchers within six months.

“We believe that the knowledge gained—together with the public release of this database in July 2006—will improve our understanding of pathophysiology and ultimately result in earlier, improved diagnostics and treatment for a broad range of diseases,” say the researchers who developed the database, from the Brain Development Cooperative Group, …
Disturbed bile secretion and cytochrome P-450 function during the acute state of experimental colitis in rats
Authors: Hans Weidenbach, Steffen Leiz, Andreas K Nussler, Nektarios Dikopoulos, Max Bachem, Klaus Buttenschoen, Max Reinshagen, Hans-G Beger, Guido Adler, Roland M Schmid
Journal: Journal of Hepatology (2000)
ABO and Rh blood groups in patients with cholelithiasis and carcinoma of the gall bladder
Authors: M Pandey, A Gautam, V K Shukla
Journal: BMJ (1995)

Carcinoma ofthe gall bladder is a common malignancy in Eastern Uttar Pradesh and Western Bihar regions of India, constituting 4 4% of all malignancies and 0 3% of admissions to University Hospital, Varanasi.'Since the first report by Aird et al in 1953,2 showing an association between blood group A and gastric cancer, numerous other reports have documented a high incidence ofblood group A in various cancers including salivary gland, colon, uterus, ovary, pancreas, kidney, bladder, and cervix.3There has been no previous report of association between gall bladder carcinoma and any specific blood group.Juvonen and Niemela4 studied 171 patients with symptomatic gall stones and found no association with any blood group, although patients with blood group A had multiple stones.Blood groups are differentially distributed in various socioeconomic, geographical, and ethnic groups.We studied the distribution of ABO and Rh blood groups in patients with carcinoma of the gall bladder and cholelithiasis, comparing it with the blood group distribution in our population.
Charles Warden Orr
Authors: J. Shores
Journal: BMJ (2003)

Former general practitioner Kingston upon Hull (b Belfast 1914; q Belfast 1939; DPH; MRCGP), d 31 January 2003.

After qualifying “Wardy” (as he was known to all his friends) served in the Royal Army Medical Corps from 1940 to 1946. He was schools and port medical officer in Hull and then medical officer of health in Thetford, Norfolk. In 1952 he returned to Hull and became senior medical officer in the school health service before joining a general practice in the centre of the city. Predeceased by his wife, Eileen, he leaves two sons and two grandchildren.
A3-07: A prospective randomized multi-center trial of three chemotherapy regimens in Korean patients with advanced non-small cell lung cancer - an interim analysis of Korean Association for The Study of Lung Cancer (KASLC)-0301 trial
Authors: Maan-Hong Jung, Young-Chul Kim, Jung-Seon Ryu, Eun-Tak Jung, Sun-Young Kim
Journal: Journal of Thoracic Oncology (2007)
Private hospitals threaten to pull out of model health insurance programme in India
Authors: G. Mudur
Journal: BMJ (2013)

Two associations of private hospitals in Andhra Pradesh have threatened to stop providing healthcare services to patients under a health insurance programme funded by the state government unless payment rates for their services are enhanced.

After months of negotiations with the state government, the associations last week imposed a 3 May deadline for an upward revision of the payment rates, which have not changed since 2007 when the Rajiv Aarogyasri health insurance scheme was launched.

The Aarogyasri scheme, initially intended to cover poor people (that is, those earning less than 60 000 rupees (£715; €842; $1100) per year), has since expanded to cover 70 million individuals, or 85% of the state population.

The government pays a premium of less than 300 rupees …
Gastrointestinal upsets associated with ingestion of copper-contaminated water.
Authors: L Knobeloch, M Ziarnik, J Howard, B Theis, D Farmer, H Anderson, M Proctor
Journal: Environmental Health Perspectives (1994)

During 1992 and 1993 the Wisconsin Division of Health investigated five cases in which copper-contaminated drinking water was suspected of causing gastrointestinal upsets. Each of these case studies was conducted after our office was notified of high copper levels in drinking water or notified of unexplained illnesses. Our findings suggest that drinking water that contains copper at levels above the federal action limit of 1.3 mg/l may be a relatively common cause of diarrhea, abdominal cramps, and nausea. These symptoms occurred most frequently in infants and young children and among resident of newly constructed or renovated homes.
Role of sympathetic nerve activity in endotoxin induced hypotension in cats
Authors: S. KOYAMA, J. W MANNING
Journal: Cardiovascular Research (1985)

Within 10 min of intravenous (iv) injection of E. coli endotoxin (1 mg X kg-1) in alpha-chloralose anaesthetised cats, mean blood pressure (MBP) fell significantly to 86% of the pre-endotoxin level. There followed a gradual decline in MBP, so that after 60 min MBP was depressed to 49% of the pre-endotoxin level. Preganglionic splanchnic nerve (PSN) activity decreased significantly before the rapid fall in MBP. There followed a gradual decrease in PSN activity coincident with the significant fall in MBP, so that 60 min after iv injection of E. coli endotoxin PSN activity fell to 40% of the pre-endotoxin level. Heart rate did not differ significantly from the pre-endotoxin level in the control group. However, the hypotension and the reduction of PSN activity following endotoxin were abolished by intracisternal (ic) pretreatment with phentolamine (0.5 mg X kg-1). The heart rate in this group increased significantly, by 15% at 10 min and was maintained until the end of the experiment. These results indicate that in E. coli endotoxin hypotension the blood pressure falls together with the reduction in sympathetic outflow; and suggests that stimulation of central alpha-adrenergic receptors leads to an inhibition of activity in brainstem sympathetic pathways.
Should the US and Russia destroy their stocks of smallpox virus?
Authors: John O Agwunobi
Journal: BMJ (2007)

Smallpox was eradicated in 1980, but the virus still exists in WHO controlled depositories. <b>Edward Hammond </b>maintains that stocks should be destroyed to prevent the disease re-emerging, but <b>John Agwunobi </b>insists further research is essential for global security
ANTIBODIES TO POLYNUCLEOTIDES IN HUMAN SERA: ANTIGENIC SPECIFICITY AND RELATION TO DISEASE
Authors: D. Koffler, R. Carr, V. Agnello, R. Thoburn, H. G. Kunkel
Journal: The Journal of Experimental Medicine (1971)

The specificities of anti-polynucleotide antibodies found in human sera were studied using several immunological procedures. Anti-native DNA (NDNA) antibodies and certain anti-double-stranded RNA (DSRNA) antibodies were found to react with single-stranded DNA (SDNA), and anti-NDNA antibodies were observed to react more avidly with SDNA than with NDNA in most sera tested. Antibodies to NDNA showed no preferential reactivity with NDNA or SDNA derived from mammalian tissue, bacterial, or viral sources. Precipitating antibodies reactive with individual bases, with common determinants of bases, and with common determinants of SDNA and NDNA were detected utilizing synthetic polydeoxyribonucleotides. Antibodies to DSRNA were also heterogeneous and reactive with both Poly A . Poly U and Poly I . Poly C in addition to reactivity with Poly A and SDNA. In contrast, antibodies to a ribonucleo-protein determined by hemagglutination and by precipitation showed no reaction with NDNA, SDNA, or DSRNA. Serial studies of serum specimens from patients with systemic lupus erythematosus (SLE) indicated that anti-NDNA antibodies were closely associated with disease activity. Titers of antibodies to SDNA or DSRNA were also frequently increased during these periods but in addition showed peaks during quiescent periods. Anti-NDNA antibodies were detected in most patients' sera at sometime during the course of the disease. Three patients were observed with active SLE, who did not develop anti-NDNA antibodies, even in the presence of severe renal disease. Evidence that other antigen-antibody systems may also play a role in the pathogenesis of the renal disease was particularly apparent in these patients. Anti-ribonucleoprotein antibodies were not well correlated with the peaks of antibody activity of other polynucleotide antibodies, suggesting that an independent immunogen was responsible for induction of these antibodies. The close association of certain populations of anti-polynucleotide antibodies during the course of active SLE, the presence of cross-reacting antigenic determinants of SDNA, NDNA, and DSRNA, the preferential avidity of anti-NDNA antibodies for SDNA, and the frequent increase of anti-SDNA antibodies in SLE and other diseases associated with active tissue destruction suggest that SDNA is a ubiquitous antigen that may stimulate the formation of antibodies reactive with a variety of polynucleotides.
Writing a British Association of Dermatologists clinical guideline: an update on the process and guidance for authors
Authors: H.K. Bell, A.D. Ormerod
Journal: British Journal of Dermatology (2009)

This advice is aimed at the authors of British Association of Dermatologists (BAD) guidelines.The idea for developing a new topic for a BAD guideline usually comes from a member of the BAD, but could come from patient representatives or other organizations such as the Royal College of Physicians (RCP).The intention is that a guideline will be comprehensive and up-to-date, aimed at dermatologists and nurses working in clinical dermatological practice.Before proceeding, the topic must be agreed by the Therapy and Guidelines Subcommittee (T&G).
Prolonged Coma After Acetohexamide Ingestion
Authors: D. L. Cowen, B. Burtis, J. Youmans
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Acetohexamide is a relatively new oral hypoglycemic agent whose side effects following an excessive dose are still being evaluated. Consumption of acetohexamide as a suicidal agent has not been reported in the literature. A case of protracted coma introduced by the ingestion of a large quantity of acetohexamide in a suicide attempt by a young, healthy, nondiabetic person is presented. <h3>Report of a Case:—</h3> A 16-year-old Spanish-American girl was seen in the Denver General Hospital emergency room on Sept 27, 1966, at 10:30 PM, with a history of ingestion of an unknown quantity of unknown substance. The patient was lethargic but responsive. Findings from the physical examination were otherwise normal. Administration of ipecac produced emesis. Following oral administration of 30 cc of magnesium sulfate solution, the patient was discharged to her parents. The patient was readmitted at 6:50 PM on Sept 28, with a history of recent
Embolism of the Central Artery of the Retina
Authors: C. S. Jeaffreson
Journal: BMJ (1871)

infiltation.No post mortem examination was had, in consequence of his residence being fifty miles distant from Aberdeen.CASE cxcviII.-JamesClarke, aged 55, nmason, came under treat- meat on March 6th, I865, and was operated on April Ist.The stone weighed 2 ounces iA drachms, and measured 21 inches by 2 itches by I inch.With a quiet pulse, and urine both clear and opious, he went on favourably for eight days, the tongue only being dry ; yet his desire for food was natural.On the ninth day, the pulse luickened a little; but there was no tenderness or local symptom any- where, and he still took his food.On the twelfth day, he became faint, after sitting up in bed; and, continuing feeble, he expired on the evening of the thirteenth day (April 13th).Inspection revealed a collection of thick pus in the cellular tissue around the wound and neck of the bladder.The viscera of the abdomen were quite healthy.The coats of the bladder were thick and chronically inflamed.CASE cciii.-DavidStewart, aged 79, farmer, was admitted on July 7th, i866, and was operated on July 14th, The stone weighed 71 drachms, and measured IA inches by i I inches by I inches.The patient was a large-built man, with a -deep perinaeum and a large carti- laginous prostate gland; yet the blunt gorget and chloroform made the
Autosomal dominant pattern of distal subungual onychomycosis caused by Trichophyton rubrum
Authors: Nardo Zaias, Antonella Tosti, Gerbert Rebell, Rosella Morelli, Federico Bardazzi, Harlan Bieley, Martin Zaiac, Brad Glick, Bruce Paley, Miguel Allevato, Robert Baran
Journal: Journal of the American Academy of Dermatology (1996)
Influence of Body Weight on the Performance of Glomerular Filtration Rate Estimators in Subjects With Type 2 Diabetes
Authors: Richard A. Chudleigh, Gareth Dunseath, Rajesh Peter, John N. Harvey, Richard L. Ollerton, Steve Luzio, David R. Owens
Journal: Diabetes Care (2007)

The American Diabetes Association recommends estimation of glomerular filtration rate (GFR) (1) by either the Cockcroft-Gault (2) or the Modification of Diet in Renal Disease (MDRD) (3) equation in all patients with diabetes. The implication is that these equations provide similar results. Body weight is a numerator in the Cockcroft-Gault equation; however, it is absent from the MDRD equation. This may explain some of the difference in the ability of these equations to estimate GFR in patients with type 2 diabetes, over 80% of whom are obese (4), and may lead to discrepancies in reporting of chronic kidney disease stage (5). Our study was designed to identify whether body weight may explain variability in performance between the Cockcroft-Gault and MDRD equations in patients newly diagnosed with type 2 diabetes.