tbuckley/cabot-search huggingface dataset:
Risk Factors and Tumor Characteristics of Interval Cancers by Mammographic Density
Authors: Johanna Holm, Keith Humphreys, Jingmei Li, Alexander Ploner, Abbas Cheddad, Mikael Eriksson, Sven Törnberg, Per Hall, Kamila Czene
Journal: Journal of Clinical Oncology (2015)

To compare tumor characteristics and risk factors of interval breast cancers and screen-detected breast cancers, taking mammographic density into account.Women diagnosed with invasive breast cancer from 2001 to 2008 in Stockholm, Sweden, with data on tumor characteristics (n = 4,091), risk factors, and mammographic density (n = 1,957) were included. Logistic regression was used to compare interval breast cancers with screen-detected breast cancers, overall and by highest and lowest quartiles of percent mammographic density.Compared with screen-detected breast cancers, interval breast cancers in nondense breasts (≤ 20% mammographic density) were significantly more likely to exhibit lymph node involvement (odds ratio [OR], 3.55; 95% CI, 1.74 to 7.13) and to be estrogen receptor negative (OR, 4.05; 95% CI, 2.24 to 7.25), human epidermal growth factor receptor 2 positive (OR, 5.17; 95% CI, 1.64 to 17.01), progesterone receptor negative (OR, 2.63; 95% CI, 1.58 to 4.38), and triple negative (OR, 5.33; 95% CI, 1.21 to 22.46). In contrast, interval breast cancers in dense breasts (> 40.9% mammographic density) were less aggressive than interval breast cancers in nondense breasts (overall difference, P = .008) and were phenotypically more similar to screen-detected breast cancers. Risk factors differentially associated with interval breast cancer relative to screen-detected breast cancer after adjusting for age and mammographic density were family history of breast cancer (OR, 1.32; 95% CI, 1.02 to 1.70), current use of hormone replacement therapy (HRT; OR, 1.84; 95% CI, 1.38 to 2.44), and body mass index more than 25 kg/m(2) (OR, 0.49; 95% CI, 0.29 to 0.82).Interval breast cancers in women with low mammographic density have the most aggressive phenotype. The effect of HRT on interval breast cancer risk is not fully explained by mammographic density. Family history is associated with interval breast cancers, possibly indicating disparate genetic background of screen-detected breast cancers and interval breast cancers.
Coadministration of Epithelial Junction Opener JO-1 Improves the Efficacy and Safety of Chemotherapeutic Drugs
Authors: Ines Beyer, Hua Cao, Jonas Persson, Hui Song, Maximilian Richter, Qinghua Feng, Roma Yumul, Ruan van Rensburg, Zongyi Li, Ronald Berenson, Darrick Carter, Steve Roffler, Charles Drescher, André Lieber
Journal: Clinical Cancer Research (2012)

Epithelial junctions between tumor cells inhibit the penetration of anticancer drugs into tumors. We previously reported on recombinant adenovirus serotype 3-derived protein (JO-1), which triggers transient opening of intercellular junctions in epithelial tumors through binding to desmoglein 2 (DSG2), and enhances the antitumor effects of several therapeutic monoclonal antibodies. The goal of this study was to evaluate whether JO-1 cotherapy can also improve the efficacy of chemotherapeutic drugs.The effect of intravenous application of JO-1 in combination with several chemotherapy drugs, including paclitaxel/Taxol, nanoparticle albumin-bound paclitaxel/Abraxane, liposomal doxorubicin/Doxil, and irinotecan/Camptosar, was tested in xenograft models for breast, colon, ovarian, gastric and lung cancer. Because JO-1 does not bind to mouse cells, for safety studies with JO-1, we also used human DSG2 (hDSG2) transgenic mice with tumors that overexpressed hDSG2.JO-1 increased the efficacy of chemotherapeutic drugs, and in several models overcame drug resistance. JO-1 treatment also allowed for the reduction of drug doses required to achieve antitumor effects. Importantly, JO-1 coadmininstration protected normal tissues, including bone marrow and intestinal epithelium, against toxic effects that are normally associated with chemotherapeutic agents. Using the hDSG2-transgenic mouse model, we showed that JO-1 predominantly accumulates in tumors. Except for a mild, transient diarrhea, intravenous injection of JO-1 (2 mg/kg) had no critical side effects on other tissues or hematologic parameters in hDSG2-transgenic mice.Our preliminary data suggest that JO-1 cotherapy has the potential to improve the therapeutic outcome of cancer chemotherapy.
Comparison of gastrointestinal symptoms in colorectal carcinoma patients and community controls with respect to age.
Authors: R Curless, J French, G V Williams, O F James
Journal: Gut (1994)

Early diagnosis of colorectal cancer may be delayed by the wide prevalence of gastrointestinal symptoms in the general population. This study assessed, with respect to age, the frequency of gastro-intestinal symptoms in patients with colorectal carcinoma in comparison with community controls and also compared the frequency of such symptoms between 9young9 (under 70 years) and 9old9 (70 year or over) subjects. Two hundred and seventy three consecutive unselected colorectal cancer patients and 273 age and sex matched community controls were interviewed in a structured manner. Among controls, the 9old9 group compared with the 9young9 reported abdominal pain (p &lt; 0.05), mucous discharge (p &lt; 0.01), faecal incontinence (p &lt; 0.05), change in flatus production (p &lt; 0.05) significantly more often. There were no significant differences in regularity and frequency of bowel habit by age group. All the symptoms considered were significantly more common in colorectal cancer cases than controls (except abdominal bloating), but the association was less strong in the 9old9 group. This study confirms that symptoms attributable to the lower gastrointestinal tract are reported by a clinically important number of community subjects and by a significantly higher proportion of elderly people.
Tolmetin. Association with reversible renal failure and acute interstitial nephritis
Authors: S. M. Katz
Journal: JAMA (1981)

FENOPROFEN calcium and naproxen, nonsteroidal anti-inflammatory agents derived from proprionic acid, are linked to nephrotic syndrome, reversible renal failure, and acute interstitial nephritis.<sup>1,2</sup>We present here a case of reversible renal failure and acute interstitial nephritis in a patient treated with tolmetin sodium (Tolectin), a nonsteroidal anti-inflammatory agent. <h3>Report of a Case</h3> A 70-year-old woman was admitted to the hospital because of nausea, anorexia, muscle weakness, and decreased urine output of two weeks' duration. She had mild hypertension for 30 years and mild osteoarthritis for ten years. Medications were as follows: methyldopa-hydrochlorothiazide (Aldoril), 25 mg three times a day for 15 years, prazosin hydrochloride (Minipress), 1 mg twice a day for two years, and tolmetin sodium, 200 mg three times to four times a day for three months. Physical examination on admission showed blood pressure to be 150/90 mm Hg. Heart rate was regular at 80 beats per minute.
Factor VII activating protease (FSAP) exerts anti-inflammatory and anti-fibrotic effects in liver fibrosis in mice and men
Authors: Erawan Borkham-Kamphorst, Henning W. Zimmermann, Nikolaus Gassler, Ute Bissels, Andreas Bosio, Frank Tacke, Ralf Weiskirchen, Sandip M. Kanse
Journal: Journal of Hepatology (2012)
Branched-chain amino acid metabolism in heart disease: an epiphenomenon or a real culprit?
Authors: Y. Huang, M. Zhou, H. Sun, Y. Wang
Journal: Cardiovascular Research (2011)

Metabolic remodelling is an integral part of the pathogenesis of heart failure. Although much progress has been made in our current understanding of the metabolic impairment involving carbohydrates and fatty acids in failing hearts, relatively little is known about the changes and potential impact of amino acid metabolism in the onset of heart diseases. Although most amino acid catabolic activities are found in the liver, branched-chain amino acid (BCAA) catabolism requires activity in several non-hepatic tissues, including cardiac muscle, diaphragm, brain and kidney. In this review, the new insights into the regulation of cardiac BCAA catabolism and functional impact on cardiac development and physiology will be discussed along with the potential contribution of impairment in BCAA catabolism to heart diseases. A particular focus will be the new information obtained from recently developed genetic models with BCAA catabolic defects and metabolomic studies in human and animal models. These studies have revealed the potential role of BCAA catabolism in cardiac pathophysiology and have helped to distinguish BCAA metabolic defects as an under-appreciated culprit in cardiac diseases rather than an epiphenomenon associated with metabolic remodelling in the failing heart.
Oncogenic BRAF Is Required for Tumor Growth and Maintenance in Melanoma Models
Authors: Klaus P. Hoeflich, Daniel C. Gray, Michael T. Eby, Janet Y. Tien, Leo Wong, Janeko Bower, Alvin Gogineni, Jiping Zha, Mary J. Cole, Howard M. Stern, Lesley J. Murray, David P. Davis, Somasekar Seshagiri
Journal: Cancer Research (2006)

The usual paradigm for developing kinase inhibitors in oncology is to use a high-affinity proof-of-concept inhibitor with acceptable metabolic properties for key target validation experiments. This approach requires substantial medicinal chemistry and can be confounded by drug toxicity and off-target activities of the test molecule. As a better alternative, we have developed inducible short-hairpin RNA xenograft models to examine the in vivo efficacy of inhibiting oncogenic BRAF. Our results show that tumor regression resulting from BRAF suppression is inducible, reversible, and tightly regulated in these models. Analysis of regressing tumors showed the primary mechanism of action for BRAF to be increased tumor cell proliferation and survival. In a metastatic melanoma model, conditional BRAF suppression slowed systemic tumor growth as determined by in vivo bioluminescence imaging. Taken together, gain-of-function BRAF signaling is strongly associated with in vivo tumorigenicity, confirming BRAF as an important target for small-molecule and RNA interference-based therapeutics.
Glycopeptide and glycoprotein synthesis involving unprotected carbohydrate building blocks
Authors: Zhongwu Guo, Ning Shao
Journal: Medicinal Research Reviews (2005)

Abstract This review summarizes the chemical and chemoenzymatic synthesis of glycopeptides and glycoproteins using unprotected carbohydrates as key intermediates. The synthetic methods covered herein include the convergent synthesis of glycopeptides by chemoselective ligation of peptides and free glycans, solution‐ and solid‐phase synthesis of glycopeptides by sequential peptide elongation with unprotected glycosyl amino acids or short glycopeptides as building blocks, and the synthesis of glycopeptides by enzymatic and/or chemical elongation of the free glycans. The use of unprotected carbohydrates in these syntheses can circumvent the final‐stage carbohydrate deprotection, lead to highly convergent synthetic designs, and more significantly, take advantage of the commercially available free glycans isolated from nature, which could considerably facilitate the synthesis of complex glycopeptides and glycoproteins. © 2005 Wiley Periodicals, Inc.
Health Secretary Milburn refuses to renegotiate contract
Authors: Z. Kmietowiz
Journal: BMJ (2002)

Doctors' leaders predicted that the refusal by the health secretary, Alan Milburn, to renegotiate the consultants' contract would cause anger among consultants.

Speaking at a press briefing last Friday, Dr Ian Bogle, chairman of the BMA council, said consultants would not be encouraged by the fact that Mr Milburn's first words on entering the meeting–the first with the secretary of state since consultants rejected the proposed new contract–were that there would be no renegotiation.

However, they would be cheered, said Dr Bogle, that Mr …
Estimating Mean Glomerular Volume Using Two Arbitrary Parallel Sections
Authors: Behzad Najafian, John M. Basgen, Michael Mauer
Journal: Journal of the American Society of Nephrology (2002)

The most reliable method for estimation of mean glomerular volume (MGV), the disector/Cavalieri method, is technically demanding and time consuming. Other methods suffer either from a lack of precise correlation with the gold standard or from the need for a large number of glomeruli in the sample. Here, a new method (the 2-profile method) is described; it provides a reliable estimate of MGV by measuring the profile area of glomeruli in two arbitrary parallel sections. MGV was estimated in renal biopsies from 16 diabetic patients and 13 normal subjects using both the Cavalieri and the 2-profile methods. The range of individual glomerular volumes based on the Cavalieri measurements was 0.31 to 4.02 x10(6) micro m(3). There was a high correlation between the two methods for MGV (r = 0.97; P < 0.0001). However, the 2-profile method systematically overestimated MGV (P = 0.0005, paired t test). This overestimation was corrected by introducing a multiplication factor of 0.91, after which statistical criteria of interchangeability with the Cavalieri method were met. The optimal distance between two sections was determined as 20 micro m with a coefficient of variation of 7.4% in repeated measurements of MGV. On the basis of findings that values for MGV stabilize after ten glomeruli are measured by the disector/Cavalieri method, it was determined that the accuracy of MGV by the 2-profile method obtained by eight glomeruli was less than 7% different from ten in all cases. Thus, the 2-profile method is a practical alternative to the disector/Cavalieri method for estimating MGV, especially in small samples and blocks with limited residual tissue.
Role of anorectal sensation in preserving continence.
Authors: M G Read, N W Read
Journal: Gut (1982)

The role of anal sensation in preserving continence was studied in nine healthy volunteers. Objective assessment of sphincter function by manometry and rectal saline infusion was carried out during topical anaesthesia of the anal canal using 5% lignocaine gel and during lubrication with the same amount of inert gel. Anaesthesia successfully abolished anal sensation and reduced both the amplitude and duration of the voluntary squeeze. Basal pressure was unaffected, but the rectal volume required to produce a sustained internal sphincter relaxation was increased. Saline continence was not impaired. Indeed, two subjects, who were previously unable to retain the full 1500 ml of rectally infused saline, did so when the anal canal was anaesthetised. Our findings suggest that anal sensation is not a critical factor in preserving continence. This implies that the incontinence experienced after anorectal surgery or neuropathy cannot be explained by lack of anal sensation alone.
Antagonism of the complement component C4 by flavivirus nonstructural protein NS1
Authors: Panisadee Avirutnan, Anja Fuchs, Richard E. Hauhart, Pawit Somnuke, Soonjeon Youn, Michael S. Diamond, John P. Atkinson
Journal: The Journal of Experimental Medicine (2010)

The complement system plays an essential protective role in the initial defense against many microorganisms. Flavivirus NS1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. Herein, we demonstrate that dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV) NS1 attenuate classical and lectin pathway activation by directly interacting with C4. Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection.
COMBINED NON-INVASIVE FUNCTIONAL AND ANATOMICAL DIAGNOSTIC WORK-UP IN CLINICAL PRACTICE: THE MAGNETIC RESONANCE AND COMPUTED TOMOGRAPHY IN SUSPECTED CORONARY ARTERY DISEASE (MARCC) STUDY
Authors: Jan Groothuis, Aernout M. Beek, Stijn L. Brinckman, Martijn R. Meijerink, Mijntje L. van den Oever, Mark M. Hofman, Cornelis van Kuijk, Albert C. van Rossum
Journal: Journal of the American College of Cardiology (2011)
Acute promyelocytic leukaemia (M3): Relapse with acute myeloblastic leukaemia (M2) and dic(5;17) (q11; p11)
Authors: Theodore Hatzis, Graham R. Standen, Rodney T. Howell, Catherine Savill, Michael Wagstaff, Geoffrey L. Scott
Journal: American Journal of Hematology (1995)

Secondary leukaemia following treatment of M3 acute promyelocytic leukaemia (APL) is a rare event. We describe a patient in remission following chemotherapy for APL who relapsed with M2 acute non-lymphoblastic leukaemia (ANLL). The original t(15;17) (q22;q21) chromosome translocation was lost and replaced by a clone containing a dic(5;17) (q11;p11) abnormality. Southern genomic analysis demonstrated re-arrangements of the retinoic acid receptor varies; is directly proportional to (RAR varies; is directly proportional to) and PML genes in the APL blasts at presentation but not in the M2 ANLL marrow at relapse. The significance of unbalanced 5;17 translocations as markers for therapy-related secondary leukaemia is discussed.
Prospective evaluation of efficacy and safety of pleuroscopy for pleural effusion
Authors: Jenny Ngai, Alvin Tung, Susanna Ng, Fanny Ko, David Hui
Journal: European Respiratory Journal (2014)

Background: Pleuroscopy is a minimal invasive procedure with increasing popularity among pulmonologist

Objective: A prospective study to assess the efficacy and safety for pleuroscopy in diagnosis of pleural effusion and talc poudrage for malignant pleural effusion.

Methods: From July 2009-June 2013, all patients undergo pleuroscopy for diagnostic or therapeutic indications were included and followed up for 6 months. Clinical data including diagnostic yield, complication and outcome were recorded prospectively.

Result: 81 patients were recruited. Overall diagnostic yield was 90% [89.5%(34/38) for malignant disease, 91.7%(11/12) for benign disease and 85.7% (6/7)for TB pleuritis]. Minor complications including talc related fever (0.14%), prolonged air leak (0.04%), increase oxygen consumption (0.01%) and CO2 retention (0.01%) were observed. No mortality or major complication occurred. Minimal sedation was given: average dose of pethidine, fentanyl and dormicum were 48.8mg(SD6.57), 13.1mcg(SD19.06) and 0.45mg(SD0.79) respectively. Duration of chest drain and length of stay were 1.98 days(SD1.42) and 5.1 days(SD2.8) respectively. Total 51 talc poudrage were done with average dose of talc was 4.47g(SD0.97). 19 patients had talc poudrage base on macroscopic appearance of pleura before histological diagnosis. Success rates with pleuroscopic talc pleurodesis for malignant pleural effusions were 86.7%, 72.5% and 64.7% at 1, 3 and 6 months respectively. 15 patients died within the follow up period.

Conclusion: Pleuroscopy is a safe procedure with high diagnostic yield for undiagnosed pleural effusion and efficacious procedure for talc poudrage in malignant pleural effusion.
Mechanisms of action of rapamycin in gliomas
Authors: Amy B. Heimberger, Enze Wang, Eric C. McGary, Kenneth R. Hess, Verlene K. Henry, Tadahisa Shono, Zvi Cohen, Joy Gumin, Raymond Sawaya, Charles A. Conrad, Frederick F. Lang
Journal: Neuro-Oncology (2005)

Rapamycin has previously been shown to be effi cacious against intracerebral glioma xenografts and to act in a cytostatic manner against gliomas.However, very little is known about the mechanism of action of rapamycin.The purpose of our study was to further investigate the in vitro and in vivo mechanisms of action of rapamycin, to elucidate molecular end points that may be applicable for investigation in a clinical trial, and to examine potential mechanisms of treatment failure.In the phos-
Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow
Authors: Hongmei Li, Qinxi Guo, Taeko Inoue, Vinicia A Polito, Katsuhiko Tabuchi, Robert E Hammer, Robia G Pautler, George E Taffet, Hui Zheng
Journal: Molecular Neurodegeneration (2014)

Accumulation and deposition of β-amyloid peptides (Aβ) in the brain is a central event in the pathogenesis of Alzheimer's disease (AD). Besides the parenchymal pathology, Aβ is known to undergo active transport across the blood–brain barrier and cerebral amyloid angiopathy (CAA) is a prominent feature in the majority of AD. Although impaired cerebral blood flow (CBF) has been implicated in faulty Aβ transport and clearance, and cerebral hypoperfusion can exist in the pre-clinical phase of Alzheimer's disease (AD), it is still unclear whether it is one of the causal factors for AD pathogenesis, or an early consequence of a multi-factor condition that would lead to AD at late stage. To study the potential interaction between faulty CBF and amyloid accumulation in clinical-relevant situation, we generated a new amyloid precursor protein (APP) knock-in allele that expresses humanized Aβ and a Dutch mutation in addition to Swedish/London mutations and compared this line with an equivalent knock-in line but in the absence of the Dutch mutation, both crossed onto the PS1M146V knock-in background. Introduction of the Dutch mutation results in robust CAA and parenchymal Aβ pathology, age-dependent reduction of spatial learning and memory deficits, and CBF reduction as detected by fMRI. Direct manipulation of CBF by transverse aortic constriction surgery on the left common carotid artery caused differential changes in CBF in the anterior and middle region of the cortex, where it is reduced on the left side and increased on the right side. However these perturbations in CBF resulted in the same effect: both significantly exacerbate CAA and amyloid pathology. Our study reveals a direct and positive link between vascular and parenchymal Aβ; both can be modulated by CBF. The new APP knock-in mouse model recapitulates many symptoms of AD including progressive vascular and parenchymal Aβ pathology and behavioral deficits in the absence of APP overexpression.
Contraception and HIV infection in women
Authors: O. Heikinheimo, P. Lahteenmaki
Journal: Human Reproduction Update (2008)

More than 15 million women, many of reproductive age, were infected with human immunodeficiency virus (HIV) at the end of 2007. As the HIV epidemic evolves, heterosexual intercourse is increasingly risky: the risk of infection in exposed young women is 4- to 7-fold higher than in young men and nearly half a million newborns annually have HIV. This review aims to show the effect of contraceptive choices on risk of HIV and on the course of disease in women with HIV.