tbuckley/cabot-search huggingface dataset:
Molecular detection of bacterial contamination in gnotobiotic rodent units
Authors: Christopher D Packey, Michael T Shanahan, Sayeed Manick, Maureen A Bower, Melissa Ellermann, Susan L Tonkonogy, Ian M Carroll, R Balfour Sartor
Journal: Gut Microbes (2013)

Gnotobiotic rodents provide an important technique to study the functional roles of commensal bacteria in host physiology and pathophysiology. To ensure sterility, these animals must be screened frequently for contamination. The traditional screening approaches of culturing and Gram staining feces have inherent limitations, as many bacteria are uncultivable and fecal Gram stains are difficult to interpret. Thus, we developed and validated molecular methods to definitively detect and identify contamination in germ-free (GF) and selectively colonized animals. Fresh fecal pellets were collected from rodents housed in GF isolators, spontaneously contaminated ex-GF isolators, selectively colonized isolators and specific pathogen-free (SPF) conditions. DNA isolated from mouse and rat fecal samples was amplified by polymerase chain reaction (PCR) and subjected to quantitative PCR (qPCR) using universal primers that amplify the 16S rRNA gene from all bacterial groups. PCR products were sequenced to identify contaminating bacterial species. Random amplification of polymorphic DNA (RAPD) PCR profiles verified bacterial inoculation of selectively colonized animals. These PCR techniques more accurately detected and identified GF isolator contamination than current standard approaches. These molecular techniques can be utilized to more definitively screen GF and selectively colonized animals for bacterial contamination when Gram stain and/or culture results are un-interpretable or inconsistent.
Gastric Necrosis: A Complication of Endoscopic Sclerosis for Bleeding Peptic Ulcer
Authors: John Chester, Paul Hurley
Journal: Endoscopy (1990)

See also: An Unusual Complication of SclerotherapyEndoscopy 1991; 23(06): 352-353DOI: 10.1055/s-2007-1010718 See also: Endoscopic Haemostasis by Injection-Therapy in High-risk PatientsEndoscopy 1982; 14(06): 196-199DOI: 10.1055/s-2007-1021620
Fluorouracil vs Gemcitabine Chemotherapy Before and After Fluorouracil-Based Chemoradiation Following Resection of Pancreatic Adenocarcinoma
Authors: William F. Regine, Kathryn A. Winter, Ross A. Abrams, Howard Safran, John P. Hoffman, Andre Konski, Al B. Benson, John S. Macdonald, Mahesh R. Kudrimoti, Mitchel L. Fromm, Michael G. Haddock, Paul Schaefer, Christopher G. Willett, Tyvin A. Rich
Journal: JAMA (2008)

Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil.To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma.Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions.Chemotherapy with either fluorouracil (continuous infusion of 250 mg/m2 per day; n = 230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n = 221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy).Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity.A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n = 388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P = .09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P = .05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P < .001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85%).The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant.clinicaltrials.gov Identifier: NCT00003216.
Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms.
Authors: H Hu, M Rabinowitz, D Smith
Journal: Environmental Health Perspectives (1998)

The skeleton contains the majority of the body's lead burden in both children and adults. The half-life of lead in bone is in the range of years to decades, depending on bone type, metabolic state, and subject age, among other things. Measurement of skeletal lead has benefited greatly from the recent development of X-ray fluorescence (XRF) instruments that can make rapid, safe, accurate, and relatively precise measurements of lead in bone. Two types of XRF technologies exist, LXRF and KXRF; this paper focuses on KXRF, which has been the most widely validated and used. KXRF is proving to be a powerful analytical methodology for evaluating bone lead levels as a measure of time-integrated (i.e., cumulative) lead dose in epidemiologic studies of the effects of chronic lead exposure. However, insufficient attention has been given to conceptualizing the paradigms by which bone lead levels reflect lead exposure and by which the skeleton serves as an endogenous source of lead. Consideration of these paradigms, which rely on bone lead kinetics, is necessary for the proper development of a priori hypotheses involving bone lead accumulation and release, the selection of bone sites for measurement by KXRF, and the design of epidemiologic studies involving bone lead dynamics. We discuss and present supporting evidence for a conceptual model that distinguishes two major paradigms of skeletal lead, including 1) bone lead as an indicator of cumulative lead exposure (bone lead as repository), and 2) bone lead as a source of body lead burden that is mobilizable into the circulation (bone lead as source). These two roles are not mutually exclusive. Instead, they are components of the processes controlling lead accumulation into and release from bone over time. Developing successful strategies for distinguishing these two processes in epidemiologic studies will require separate measurements of lead in cortical and trabecular bone and additional measurement of specific markers of bone mineral turnover and resorption. It may also involve developing accurate methods for evaluating lead in labile compartments of the circulation, such as plasma, as a potentially useful and responsive measure of bone lead release, of the partitioning of circulatory lead, and of the toxicological significance of lead released from bone to other target organs.
Serial Bone Scans in the Assessment of Response to Therapy in Advanced Breast Carcinoma
Authors: M A ROSSLEIGH, F T A LOVEGROVE, P M REYNOLDS, M J BYRNE
Journal: Clinical Nuclear Medicine (1982)

Twenty-seven patients taking part in an advanced breast cancer trial in Australia and New Zealand were studied to assess the predictive value of serial bone scans as an indicator of response to therapy. The report of serial bone scans in 20 of the 27 patients correctly reflected the clinical outcome. Of the 20 patients, all had an initial subjective response and 15 had an objective response. Of the seven patients whose bone scan report did not reflect the clinical situation, five had increased uptake in known lesions and new lesions and one had increased uptake in known lesions only within six months of commencing therapy. These scan reports indicated progression of disease rather than a healing or "flare" response which was later proved to exist. One patient had clinical progression of bone metastases which was confirmed by x-ray but was not reflected in the bone scan until months later. Clinical progression of disease was accurately reflected in the bone scans of 11 of 12 patients. Recognition that a "'flare" effect in the first months of therapy may also cause new lesions to be seen should enhance the accuracy of bone scintigraphy.
Lipids and stroke: neglect of a useful preventive measure?
Authors: J Papadakis
Journal: Cardiovascular Research (1998)

The epidemiological studies linking lipid variables and stroke are reviewed. These studies indicate that serum total cholesterol (TC) levels are associated positively with thrombotic and negatively with haemorrhagic strokes. Relationships for other lipid fractions are not as clearly defined. The results of trials with lipid lowering drugs suggest that only statins effectively reduce the incidence of stroke. Differences between trial results may be due to variation in the extent of reduction of TC levels. Possible underlying mechanisms for benefit and the apparent superiority of statins are also discussed. The reduction in the risk of thrombotic stroke with statins is most evident through meta-analyses (p<0.001) and less impressive in individual trials (p<0.03). This difference is largely attributable to the small number of events in trials primarily aimed at evaluating ischaemic heart disease (IHD) reduction. This also means that benefit may be limited to those with established IHD. IHD and thrombotic stroke share common risk factors and patients with one condition are at high risk of developing the other. Therefore, one additional reason for using statins in these patients is that these drugs can effectively prevent IHD-related events including deaths.
Epidemiology of hepatitis C and G in sporadic and familial porphyria cutanea tarda
Authors: Jérôme Lamoril, Christophe Andant, Catherine Bogard, Hervé Puy, Laurent Gouya, Jean-Michel Pawlotsky, Vasco Da Silva, Jean-Claude Soulé, Jean-Charles Deybach, Yves Nordmann
Journal: Hepatology (1998)

From 1995 to 1997, we prospectively evaluated the prevalence of hepatitis C virus (HCV) RNA in 124 patients with porphyria cutanea tarda (PCT) from Northern France (83 sporadic and 41 familial PCT). Serum samples were analyzed for ferritin, transaminases, HCV antibodies, and HCV RNA. In addition, genotyping of HCV and searches for HCV infection risk factors (blood transfusion, iv drug abuse, and surgical intervention) were performed. Twenty-six of 124 patients (21%; 95% CI: 13.9-28) were positive for serum HCV antibodies. All of them were also positive for HCV RNA. The prevalence of HCV infection was higher in the sporadic PCT group (26.5%, 22 out of 83) than in the familial PCT group (9.7%, 4 out of 41). Risk factors for hepatitis C infection were found to be significantly increased in the HCV-positive group when compared with the HCV-negative PCT group. In all HCV-positive patients with a risk factor, the suspected date of exposure to the virus always preceded the clinical onset of PCT. The HCV genotype pattern in PCT patients was similar to that observed in nonporphyric HCV patients in western European countries. Serum ferritin level was increased in both HCV-positive and HCV-negative porphyric patients. Transaminase levels were significantly higher in HCV-infected PCT patients. Sixty-seven out of 124 patients were retrospectively studied for hepatitis G virus (HGV) infection. Six of these 67 patients (8.9%; 95% CI: 2.1-15.8) were positive for HGV RNA. None of the six HGV-infected patients were positive for HCV RNA. The HGV-infected patients did not differ statistically from those without HGV infection with regard to age, ferritin, transaminase levels, and PCT treatment. These results support the view that sporadic cases of HGV infection may occur frequently. This study of a large cohort of HCV and PCT patients further documents an increasing gradient in HCV prevalence from northern to southern Europe, and shows that HCV infection acts as a triggering factor of PCT. Finally, the HGV prevalence found in the PCT patients was comparable with that found in French blood donors, suggesting that HGV is not a PCT triggering factor.
Yin Yang-1 Inhibits Vascular Smooth Muscle Cell Growth and Intimal Thickening by Repressing p21 <sup>WAF1/Cip1</sup> Transcription and p21 <sup>WAF1/Cip1</sup> -Cdk4-Cyclin D1 Assembly
Authors: Fernando S. Santiago, Hideto Ishii, Shahida Shafi, Rohit Khurana, Peter Kanellakis, Ravinay Bhindi, Manfred J. Ramirez, Alexander Bobik, John F. Martin, Colin N. Chesterman, Ian C. Zachary, Levon M. Khachigian
Journal: Circulation Research (2007)

Vascular injury initiates a cascade of phenotype-altering molecular events. Transcription factor function in this process, particularly that of negative regulators, is poorly understood. We demonstrate here that the forced expression of the injury-inducible GLI-Krüppel zinc finger protein Yin Yang-1 (YY1) inhibits neointima formation in human, rabbit and rat blood vessels. YY1 inhibits p21 WAF1/Cip1 transcription, prevents assembly of a p21 WAF1/Cip1 -cdk4-cyclin D1 complex, and blocks downstream pRb Ser249/Thr252 phosphorylation and expression of PCNA and TK-1. Conversely, suppression of endogenous YY1 elevates levels of p21 WAF1/Cip1 , PCNA, pRb Ser249/Thr252 and TK-1, and increases intimal thickening. YY1 binds Sp1 and prevents its occupancy of a distinct element in the p21 WAF1/Cip1 promoter without YY1 itself binding the promoter. Additionally, YY1 induces ubiquitination and proteasome-dependent degradation of p53, decreasing p53 immunoreactivity in the artery wall. These findings define a new role for YY1 as both an inducer of p53 instability in smooth muscle cells, and an indirect repressor of p21 WAF1/Cip1 transcription, p21 WAF1/Cip1 -cdk4-cyclin D1 assembly and intimal thickening.
Abstract A38: Therapeutic effect of epigallocatechin-3-gallate and silibinin on ATM dynamics in prostate cancer cell line LNCaP
Authors: A. A. Farooqi, Sadia Rashid, Taskeen M. Mashadi, Shahzad Bhatti, M. Saleem
Journal: Clinical Cancer Research (2010)

Abstract Epigallocatechin-3-gallate (EGCG) is a major ingredient of green tea (GT) and silibinin, the active component of silymarin presumably hold a potential to prevent pathogenomics. Prostate cancer exacerbation is triggered by fusion transcripts formed because of genomic instability induced by juxtapositioning of two genes. An abolished ATM dynamics challenges integrity of DNA. In agreement with this assumption ATM and ATR were impaired in LNCaP cell line to confirm a tight interaction of ATM and ATR with the expression profile of TMPRSS2-ERG. Abolished ATM enhanced the expression of the fusion transcript. Similarly blunting of ATR downregulated the expression the fusion transcript giving a notion that ATR is involved in the chromosomal translocation. LNCaP cell lines were analyzed for the effect of EGCG and silibinin on the expression profile of TMPRSS2- ERG. In this particular study treatment of the LNCaP cell line with EGCG and Silibilin recapitulated ATM expression and activity and downregulated the fusion transcript expression. These results underscore the therapeutic effect of EGCG and SB in attenuating the exacerbation of the disease. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A38.
Sex Differences in Combined Drug Response
Authors: Michael W. LaSalle
Journal: JAMA (1966)

To the Editor:—  There have been very few references in the literature to a sex difference in response to drugs. The most germane to this communication is cited in Krantz and Cass'sPharmacologic Principles of Medical Practice, where ephedrine alkaloids are said to be more likely to cause nervousness in women than in men. Other papers noting a sexual difference in drug response are listed at the end of this letter.1-7Below is a brief description of such a sexual difference in response to a combination of antihistamine and ephedrine alkaloid.  The subjects consisted of 25 healthy, young, human adults. Seven received a placebo on a double-blind, randomized basis; the other 18 received a preparation which consisted of twice the normal dosages of both a brompheniramine antihistamine and an ephedrine alkaloid. Five women and 13 men received the active preparation. Of the women, four noticed nervousness, excitement, or insomnia.
Home vs Hospital Care for Schizophrenics
Authors: B. Pasamanick, F. R. Scarpitti, M. Lefton, S. Dinitz, J. J. Wernert, H. McPheeters
Journal: JAMA (1964)

In order to evaluate the effects of the treatment of schizophrenics at home under public health nursing care and a drug regimen, 193 patients were randomly assigned to either a drug home care group, a placebo home care group, or a hospital control group. The findings in the first 18 months of the program indicate that: (1) the drug patients have been more successful in remaining at home than the placebo cases, (2) this superiority increases with length of time on the project and, (3) home care patients, drug and placebo, spend a greater percentage of treatment time at home than those patients assigned to the hospital control group. Family, economic, and psychiatric problems encountered by patients remaining in the community indicate the need for a more comprehensive program.
Urinary Precipitate During Cephalothin-Cephaloridine Treatment
Authors: Micha Levy
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The cephalosporins are semisynthetic congeners of cephalosporin C which is produced by the fungus<i>Cephalosporium acremonium</i>. The most commonly used representatives of this group of new antibiotics are cephalothin sodium and cephaloridine; both are excreted unchanged in the urine.<sup>1,2</sup>Urinary recovery studies on normal subjects given single intramuscular injections of 1.0 gm of either cephalothin sodium or cephaloridine indicate that about 75% of the injected material is eliminated in an active form during the first six hours.<sup>2</sup>Cephaloridine is excreted almost entirely by glomerular filtration<sup>3</sup>although tubular excretion also occurs.<sup>4</sup>Renal dysfunction may occur during treatment with cephaloridine and, less frequently, with cephalothin.<sup>5</sup>Acute toxic effects of cephaloridine include necrosis of the proximal convoluted tubules in mice, rats, guinea pigs, rabbits, monkeys, and man.<sup>5-9</sup>Repeated administration in rats of 50 to 150 mg/kg/day of cephaloridine produces proteinuria,<sup>10</sup>while moderate to large
Abstract 5301: Rescuing cell polarity with small molecule inhibitors of de-palmitoylation
Authors: Jeannie L. Hernandez, Dahvid Davda, Jaimeen Majmudar, Kristin J. Labby, Margery Gang, Sirisha Pasupuleti, Makoto Seita, Brent R. Martin
Journal: Cancer Research (2014)

Abstract Protein palmitoylation is a unique post-translational modification required for the membrane anchoring and trafficking of numerous regulatory proteins that play key roles in cell growth, polarity, and signaling. Using a pulse-chase palmitoylation proteomics approach, we identified the tumor suppressor Scrib as the most dynamic, enzymatically regulated palmitoylated protein in malignant cells. Scrib localizes at the basolateral membrane where it regulates epithelial cell apical-basolateral polarity, junctional integrity, proliferation, and metastasis. Loss of Scrib at the plasma membrane cooperates with oncogenic Ras or Myc overexpression to drive tumor formation, promote epidermal to mesenchymal transition (EMT), and bypass contact inhibition. Interestingly, overexpression of Snail in polarized cells eliminates Scrib membrane localization. We recently reported a class of in vivo active small selective inhibitors of the acyl protein thioesterases APT1 and APT2. Addition of a small molecule APT2 inhibitor restores Scrib membrane localization and enhances E-Cadherin expression, overcoming Snail-mediated repression of E-cad. These findings suggest that thioesterases, predominantly APT2 more than APT1, regulate the palmitoylation of cell polarity proteins, and highlight a strategy to attenuate oncogenic signaling and restore cell polarity pathways in malignant cells. Citation Format: Jeannie L. Hernandez, Dahvid Davda, Jaimeen Majmudar, Kristin J. Labby, Margery Gang, Sirisha Pasupuleti, Makoto Seita, Brent R. Martin. Rescuing cell polarity with small molecule inhibitors of de-palmitoylation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5301. doi:10.1158/1538-7445.AM2014-5301
On Complete Removal of the Prostate
Authors: W. W. Galbraith
Journal: BMJ (1947)

Sir,-In the Journal of May 31 (p. 779) a letter by Dr. L. F. Donnan was published in which it was stated that I had informed the writer that the relapse rate after insuhn treatment for schizophrenia is greater than in those cases which recovered spontaneously. This statement was not made by me to Dr. Donnan or to anyone else. Insulin treatment of schizophrenia has been carried on in this hospital for the last ten years, and the results go to show that it is by far the most successful form of treatment for schizophrenia. Schizophrenia does not differ from any other form of disease in that a certain proportion of cases that have recovered relapse. The experience of this hospital goes to show that the rate of recovery is much greater in cases treated by insulin than by any other method and that the relapse rate shows no proportionate increase.-I am, etc.,
Can geriatrics survive?
Authors: J C Leonard
Journal: BMJ (1976)

Geriatrics has consistently failed to attract enough staff, and hence geriatric units often cannot provide a full service for the elderly. Meanwhile beds in general medical units may be blocked by elderly patients. This division between geriatric and medical units is arbitrary and wasteful. There are no clinical processes or techniques unique to geriatrics, which is probably why the specialty is unattractive; few doctors want to confine their attention only to the elderly. Geriatrics as a separate specialty should therefore be largely abandoned and the care of the elderly reintegrated into general medicine.
Wide Frequency Range Force Ballistocardiogram
Authors: T. J. REEVES, L. L. HEFNER, W. B. JONES, J. E. SPARKS
Journal: Circulation (1957)

The ballistocardiograms of young normal subjects as recorded with a wide frequency range technic are described. These records contain high frequency forces not previously described. An analysis of these components in terms of known cardiovascular events strongly suggests that they have definite dynamic significance. In addition, these correlations offer evidence as to the genesis of some forces in the ballistocardiogram.
The Malignant Hyperthermia Syndrome
Authors: T. E. Nelson, E. H. Flewellen
Journal: New England Journal of Medicine (1983)

MALIGNANT hyperthermia was first described fully in 1962, when Denborough and colleagues reported an episode in a patient with a fear of anesthesia prompted by the death of 10 of 24 relatives who had received general anesthesia.1 A genetic susceptibility to drug-induced malignant hyperthermia was confirmed by numerous subsequent reports.2 Malignant hyperthermia is a syndrome initiated by a hypermetabolic state of skeletal muscle. The underlying defect appears to be an idiopathic increase in the sarcoplasmic concentration of calcium ion.3 4 5 As a consequence, during general anesthesia total body oxygen consumption in patients with the syndrome increases two to three times as . . .