tbuckley/cabot-search huggingface dataset:
Comment Re: MDA-MB-435 and M14 Cell Lines: Identical but not M14 Melanoma?
Authors: Antoinette Hollestelle, Mieke Schutte
Journal: Cancer Research (2009)

To the Editor: In support of the recent article by Chambers (1), we wish to share our data on the origin of the MDA-MB-435 and M14 cell lines. Chambers claims that it is most plausible that both cell lines represent MDA-MB-435 based on two X chromosomes in the MDA-MB-435 karyotype, whereas M14 had been derived from a man (1). However, karyotyping does not discriminate between paternal and maternal alleles and thus does not exclude loss of the Y chromosome combined with reduplication of the X chromosome. We previously reported an allelotype on human breast cancer cell lines, including MDA-MB-435 (2). Our analyses did not detect Y chromosome sequences and revealed heterozygosity of polymorphic microsatellite markers at Xp, implying that MDA-MB-435 had indeed been derived from a woman. Our MDA-MB-435 cell line was obtained directly from American Type Culture Collection at passage 239 and M14 from its originator at passage 10 (3). We confirmed that the cell lines were identical by microsatellite analysis, in concordance with Rae and colleagues (4), and we also identified unique mutations in the p53 and p16 genes in both cell lines (3). Altogether, it can be concluded conclusively that MDA-MB-435 and M14 are breast cancer cell lines.The melanocytic phenotype of MDA-MB-435 may be explained by our recent molecular characterization of MDA-MB-435 and 40 other human breast cancer cell lines (3). Microarray gene expression profiling had revealed two major subgroups among thebreast cancer cell lines: luminal type and basal type. As anticipated, MDA-MB-435 was basal type, along with 14 other cell lines, and unsupervised hierarchical clustering showed strong similarity among the basal-type cell lines. It is unlikely that the 15 basal-type cell lines all are of melanocytic origin because 4 of them carry a BRCA1 mutation and 1 has the CHEK2 1100delC mutation. Also, 10 of the basal-type cell lines, including MDA-MB-435, are of the normal-like intrinsic subtype; a molecular subtype that had been defined on (uncultured) clinical breast tumors. Most interestingly, analysis of the genetic status of 27 well-known cancer genes in our collection of breast cancer cell lines identified two subtype-specific gene mutation profiles (3). The basal mutation profile involved mutations in the BRCA1, RB1, RAS, and BRAF genes and deletions of p16 and p14ARF. Particularly, the combination of mutations in p16, RB1, and RAS pathway genes is characteristic for melanoma. These results thus suggest that basal-type breast cancers may have a genetic basis similar to melanomas, explaining their melanocytic phenotype and perhaps also their rather aggressive clinical course.No potential conflicts of interest were disclosed.
THE METABOLISM OF SILICON IN THE RAT AND ITS RELATION TO THE FORMATION OF ARTIFICIAL SILICEOUS CALCULI
Authors: Richard F. Keeler, Stuart A. Lovelace
Journal: The Journal of Experimental Medicine (1959)

The urinary excretion of silicon in the rat was found to be enhanced beyond normal levels by the administration of various chemical forms of silicon. The excretion was enhanced to a much greater degree by the administration of ethyl silicate than by magnesium trisilicate, sodium metasilicate, or water glass. The tolerance level of rats to sustained daily doses of ethyl silicate fed via stomach tube was approximately 15 to 30 mg. of silicon per rat per day. Urinary silicon excretion was found to be a straight line function of the concentration of ethyl silicate administered, via stomach tube, with approximately 18 per cent of the administered silicon appearing in the urine at all levels tested. Using sustained dietary additions of ethyl silicate as a means of enhancing urine silicon levels, artificial siliceous urinary calculi were consistently produced on zinc pellets implanted in the bladders of rats.
In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma
Authors: Leonie S. van Rijt, Steffen Jung, Alex KleinJan, Nanda Vos, Monique Willart, Catherine Duez, Henk C. Hoogsteden, Bart N. Lambrecht
Journal: The Journal of Experimental Medicine (2005)

Although dendritic cells (DCs) play an important role in sensitization to inhaled allergens, their function in ongoing T helper (Th)2 cell–mediated eosinophilic airway inflammation underlying bronchial asthma is currently unknown. Here, we show in an ovalbumin (OVA)-driven murine asthma model that airway DCs acquire a mature phenotype and interact with CD4+ T cells within sites of peribronchial and perivascular inflammation. To study whether DCs contributed to inflammation, we depleted DCs from the airways of CD11c-diphtheria toxin (DT) receptor transgenic mice during the OVA aerosol challenge. Airway administration of DT depleted CD11c+ DCs and alveolar macrophages and abolished the characteristic features of asthma, including eosinophilic inflammation, goblet cell hyperplasia, and bronchial hyperreactivity. In the absence of CD11c+ cells, endogenous or adoptively transferred CD4+ Th2 cells did not produce interleukin (IL)-4, IL-5, and IL-13 in response to OVA aerosol. In CD11c-depleted mice, eosinophilic inflammation and Th2 cytokine secretion were restored by adoptive transfer of CD11c+ DCs, but not alveolar macrophages. These findings identify lung DCs as key proinflammatory cells that are necessary and sufficient for Th2 cell stimulation during ongoing airway inflammation.
The Dynamics of Glomerular Ultrafiltration in the Rat
Authors: Barry M. Brenner, Julia L. Troy, Terrance M. Daugharty
Journal: Journal of Clinical Investigation (1971)

Using a unique strain of Wistar rats endowed with glomeruli situated directly on the renal cortical surface, we measured glomerular capillary pressures using servo-nulling micropipette transducer techniques. Pressures in 12 glomerular capillaries from 7 rats averaged 60 cm H(2)O, or approximately 50% of mean systemic arterial values. Wave form characteristics for these glomerular capillaries were found to be remarkably similar to those of the central aorta. From similarly direct estimates of hydrostatic pressures in proximal tubules, and colloid osmotic pressures in systemic and efferent arteriolar plasmas, the net driving force for ultrafiltration was calculated. The average value of 14 cm H(2)O is lower by some two-thirds than the majority of estimates reported previously based on indirect techniques. Single nephron GFR (glomerular filtration rate) was also measured in these rats, thereby permitting calculation of the glomerular capillary ultrafiltration coefficient. The average value of 0.044 nl sec(-1) cm H(2)O(-1) glomerulus(-1) is at least fourfold greater than previous estimates derived from indirect observations.
Hospitalizations for Pelvic Inflammatory Disease
Authors: A. Eugene Washington
Journal: JAMA (1984)

To assess trends in hospitalizations for pelvic inflammatory disease (PID) in the United States for 1975 through 1981, we analyzed data from the Hospital Discharge Survey conducted by the National Center for Health Statistics. Overall, both the estimated number and rate of hospitalizations for PID among women aged 15 to 44 years rose slightly. For the seven-year period, an estimated average of 267,200 women were hospitalized annually for PID, with hospitalization rates averaging 5.3 per 1,000 women. Risk of hospitalization for PID was greatest among women in their 20s. Divorced or separated women were considerably more likely to have been hospitalized than single or married women. Although nonwhite women had estimated average rate 2.5 times higher than for white women, the trend of hospitalizations for PID among nonwhite women appeared relatively stable while the trend among young white women showed measurable increases.
Increased frequency dependence of specific airway resistance in patients with laryngeal hemiplegia
Authors: V. Fasano, L. Raiteri, E. Bucchioni, S. Guerra, G. Cantarella, M.G. Massari, B.M. Cesana, L. Allegra
Journal: European Respiratory Journal (2001)

The aim of this study was to investigate whether patients with laryngeal hemiplegia (LH) show a frequency-dependent increase in specific airway resistance (sRaw), measured by body plethysmography. In addition to the flow-volume loop, usually considered in the functional evaluation of upper airway obstructions, variations in sRaw at respiratory frequencies of 30+/-5 (=0.5 Hz), 60+/-5 (=1 Hz) and 90+5 breaths x min(-1) (=1.5 Hz) in 21 never-smoking patients (LH group, mean age+/-SD 55+/-12.09 yrs; 17 females) whose unilateral vocal-cord paralysis was documented by laryngoscopy and who had no signs or symptoms of other respiratory diseases studied. They were compared to 21 healthy control subjects (C group: 50.1+/-15.44 yrs; 10 females). The sRaw values at 30+/-5 breaths min(-1) were similar in the two groups (5.54+/-1.88 versus 5.68+/-1.06 cmH2O x s(-1); p=NS), but at increasing frequencies (30+/-5, 60+/-5 and 90+/-5 breaths min(-1)), they progressively and significantly increased in the LH patients (from 5.54+/-1.88 to 6.63+/-1.96 and 8.05+/-2.6 mH2O x s(-1); p<0.0005), and not significantly in controls (5.68+/-1.06, 5.85+/-0.95 and 5.9+/-1.12 cmH2O x s(-1); p=NS). Linear discriminant analysis using AsRaw (sRaw at 1.5 Hz-sRaw at 0.5 Hz) and forced inspiratory flow at 50% of the vital capacity made it possible to correctly classify all of the controls and 19 of the 21 patients. In conclusion, the multiple, rapid and noninvasive plethysmographical testing of frequency-dependent increase in specific airway resistance with the flow-volume loop, allows the sufficiently satisfactory discrimination of laryngeal hemiplegia patients from controls.
Hyaluronan-CD44 Interactions in Cancer: Paradoxes and Possibilities
Authors: Bryan P. Toole
Journal: Clinical Cancer Research (2009)

Abstract Hyaluronan is a prominent component of the micro-environment in most malignant tumors and can be prognostic for tumor progression. Extensive experimental evidence in animal models implicates hyaluronan interactions in tumor growth and metastasis, but it is also evident that a balance of synthesis and turnover by hyaluronidases is critical. CD44, a major hyaluronan receptor, is commonly but not uniformly associated with malignancy, and is frequently used as a marker for cancer stem cells in human carcinomas. Multivalent interactions of hyaluronan with CD44 collaborate in driving numerous tumor-promoting signaling pathways and transporter activities. It is widely accepted that hyaluronan-CD44 interactions are crucial in both malignancy and resistance to therapy, but major challenges for future research in the field are the mechanism of activation of hyaluronan-CD44 signaling in cancer cells, the relative importance of variant forms of CD44 and other hyaluronan receptors, e.g., Rhamm, in different tumor contexts, and the role of stromal versus tumor cell production and turnover of hyaluronan. Despite these caveats, it is clear that hyaluronan-CD44 interactions are an important target for translation into the clinic. Among the approaches that show promise are antibodies and vaccines to specific variants of CD44 that are uniquely expressed at critical stages of progression of a particular cancer, hyaluronidase-mediated reduction of barriers to drug access, and small hyaluronan oligosaccharides that attenuate constitutive hyaluronan-receptor signaling and enhance chemosensitivity. In addition, hyaluronan is being used to tag drugs and delivery vehicles for targeting of anticancer agents to CD44-expressing tumor cells. (Clin Cancer Res 2009;15(24):7462–8)
Serum Proteomic Fingerprinting Discriminates Between Clinical Stages and Predicts Disease Progression in Melanoma Patients
Authors: Shahid Mian, Selma Ugurel, Erika Parkinson, Iris Schlenzka, Ian Dryden, Lee Lancashire, Graham Ball, Colin Creaser, Robert Rees, Dirk Schadendorf
Journal: Journal of Clinical Oncology (2005)

Currently known serum biomarkers do not predict clinical outcome in melanoma. S100-beta is widely established as a reliable prognostic indicator in patients with advanced metastatic disease but is of limited predictive value in tumor-free patients. This study was aimed to determine whether molecular profiling of the serum proteome could discriminate between early- and late-stage melanoma and predict disease progression.Two hundred five serum samples from 101 early-stage (American Joint Committee on Cancer [AJCC] stage I) and 104 advanced stage (AJCC stage IV) melanoma patients were analyzed by matrix-assisted laser desorption/ionisation (MALDI) time-of-flight (ToF; MALDI-ToF) mass spectrometry utilizing protein chip technology and artificial neural networks (ANN). Serum samples from 55 additional patients after complete dissection of regional lymph node metastases (AJCC stage III), with 28 of 55 patients relapsing within the first year of follow-up, were analyzed in an attempt to predict disease recurrence. Serum S100-beta was measured using a sandwich immunoluminometric assay.Analysis of 205 stage I/IV serum samples, utilizing a training set of 94 of 205 and a test set of 15 of 205 samples for 32 different ANN models, revealed correct stage assignment in 84 (88%) of 96 of a blind set of 96 of 205 serum samples. Forty-four (80%) of 55 stage III serum samples could be correctly assigned as progressors or nonprogressors using random sample cross-validation statistical methodologies. Twenty-three (82%) of 28 stage III progressors were correctly identified by MALDI-ToF combined with ANN, whereas only six (21%) of 28 could be detected by S100-beta.Validation of these findings may enable proteomic profiling to become a valuable tool for identifying high-risk melanoma patients eligible for adjuvant therapeutic interventions.
<sup>18</sup>F-Misonidazole PET-CT scan detection of occult bone metastasis
Authors: Daniel R McGowan, Ruth E Macpherson, Kevin M Bradley, John D Fenwick, Fergus V Gleeson, Geoff S Higgins
Journal: Thorax (2015)

A 67-year-old man with locally advanced non-small cell lung cancer entered a phase I trial combining a novel phosphoinositide 3-kinase inhibitor (BKM120) with palliative radiotherapy.1 The trial uses 18F-misonidazole (FMISO) positron emission tomography (PET)-CT imaging to assess any changes in tumour hypoxia. FMISO is a tracer currently only used in the research setting.

A pretreatment FMISO PET-CT scan identified an occult, asymptomatic scapular metastasis (figure 1) undetectable on routine CT imaging (figure 2A). This was subsequently confirmed …
<i>BARTONELLA</i> (<i>ROCHALIMAEA</i>) INFECTIONS: Beyond Cat Scratch
Authors: W. Schwartzman, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Five species of Bartonella have been found to infect humans, henselae, quintana, elizabethae, bacilliformis, and vinsonii. The most common of these in North America are Bartonella quintana and Bartonella henselae, the agents of trench fever, bacillary angiomatosis, and parenchymal peliosis, and in the case of B. henselae cat-scratch disease. B. bacilliformisis endemic in Peru and Ecuador, where it causes oroya fever or Carrion's disease. New methods of diagnosing Bartonella infections have resulted in increased recognition of the many manifestations of these infections. Early recognition is crucial, as these are potentially fatal opportunistic infections that usually respond rapidly to appropriate antimicrobial therapy.
Pharmaceutical and Toxicological Properties of Engineered Nanomaterials for Drug Delivery
Authors: Matthew Palombo, Manjeet Deshmukh, Daniel Myers, Jieming Gao, Zoltan Szekely, Patrick J. Sinko
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Novel engineered nanomaterials (ENMs) are being developed to enhance therapy. The physicochemical properties of ENMs can be manipulated to control/direct biodistribution and target delivery, but these alterations also have implications for toxicity. It is well known that size plays a significant role in determining ENM effects since simply nanosizing a safe bulk material can render it toxic. However, charge, shape, rigidity, and surface modifications also have a significant influence on the biodistribution and toxicity of nanoscale drug delivery systems (NDDSs). In this review, NDDSs are considered in terms of platform technologies, materials, and physical properties that impart their pharmaceutical and toxicological effects. Moving forward, the development of safe and effective nanomedicines requires standardized protocols for determining the physical characteristics of ENMs as well as assessing their potential long-term toxicity. When such protocols are established, the remarkable promise of nanomedicine to improve the diagnosis and treatment of human disease can be fulfilled.
Angiotensin II and tumour necrosis factor α as mediators of ATP-dependent potassium channel remodelling in post-infarction heart failure
Authors: Nadia Isidoro Tavares, Pierre Philip-Couderc, Alex J. Baertschi, René Lerch, Christophe Montessuit
Journal: Cardiovascular Research (2009)

Angiotensin II (Ang II) and tumour necrosis factor α (TNFα) are involved in the progression from compensated hypertrophy to heart failure. Here, we test their role in the remodelling of ATP-dependent potassium channel (KATP) in heart failure, conferring increased metabolic and diazoxide sensitivity. We observed increased expression of both angiotensinogen and TNFα in the failing rat myocardium, with a regional gradient matching that of the KATP subunit Kir6.1 expression. Both angiotensinogen and TNFα expression correlated positively with Kir6.1 and negatively with Kir6.2 expression across the post-infarction myocardium. To further identify a causal relationship, cardiomyocytes isolated from normal rat hearts were exposed in vitro to Ang II or TNFα. We observed increased Kir6.1 and SUR subunit and reduced Kir6.2 subunit mRNA expression in cardiomyocytes cultured with Ang II or TNFα, similar to what was observed in failing hearts. In patch-clamp experiments, cardiomyocytes cultured with Ang II or TNFα exhibited responsiveness to diazoxide, in terms of both KATP current and action potential shortening. This was not observed in untreated cardiomyocytes and resembles the diazoxide sensitivity of failing cardiomyocytes that also overexpress Kir6.1. Ang II exerted its effect through induction of TNFα expression, because TNFα-neutralizing antibody abolished the effect of Ang II, and in failing hearts, regional expression of angiotensinogen matched TNFα expression. Finally, Ang II and TNFα regulated KATP subunit expression, possibly through differential expression of Forkhead box transcription factors. This study identifies Ang II and TNFα as mediators of the remodelling of KATP channels in heart failure.
Role of 15-DeoxyΔ<sup>12,14</sup> Prostaglandin J<sub>2</sub> and Nrf2 Pathways in Protection against Acute Lung Injury
Authors: Mie Mochizuki, Yukio Ishii, Ken Itoh, Takashi Iizuka, Yuko Morishima, Toru Kimura, Takumi Kiwamoto, Yosuke Matsuno, Ahamed E. Hegab, Akihiro Nomura, Tohru Sakamoto, Koji Uchida, Masayuki Yamamoto, Kiyohisa Sekizawa
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Acute lung injury (ALI) is a disease process that is characterized by diffuse inflammation in the lung parenchyma. Recent studies demonstrated that cyclooxygenase-2 (COX-2) induced at the late phase of inflammation aids in the resolution of inflammation by generating 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2). Transcription factor Nrf2 is activated by electrophiles and exerts antiinflammatory effects by inducing the gene expression of antioxidant and detoxification enzymes.Because 15d-PGJ2 is an endogenous electrophile, we hypothesized that it protects against ALI by activating Nrf2.To test this hypothesis, we generated a reversible ALI model by intratracheal injection of carrageenin, an inducer of acute inflammation, whose stimulation has been known to induce COX-2.We found that ALI induced by carrageenin was markedly exacerbated in Nrf2-knockout mice, compared with wild-type mice. Analysis of bronchoalveolar lavage fluids also revealed that the magnitude and the duration of acute inflammation, indicated by albumin concentration and the number of neutrophils, were significantly enhanced in Nrf2-knockout mice. Treatment of wild-type mice with NS-398, a selective COX-2 inhibitor, significantly exacerbated ALI to the level of Nrf2-knockout mice. In the lungs of NS-398-treated wild-type mice, both the accumulation of 15d-PGJ2 and the induction of Nrf2 target antioxidant genes were significantly attenuated. Exogenous administration of 15d-PGJ2 reversed the exacerbating effects of NS-398 with the induction of antioxidant genes.These results demonstrated in vivo that 15d-PGJ2 plays a protective role against ALI by exploiting the Nrf2-mediated transcriptional pathway.
Chronic intrahepatic cholestasis due to sarcoidosis.
Authors: N M Bass, A K Burroughs, P J Scheuer, D G James, S Sherlock
Journal: Gut (1982)

Two West Indian patients with Kveim-biopsy proven sarcoidosis developed chronic cholestatic liver disease, clinically and biochemically similar to primary biliary cirrhosis. Liver histology revealed multiple granulomas with reduction in bile ducts and, in one patient, progression to biliary cirrhosis. Portal hypertension was present in both patients leading to severe variceal haemorrhage in one. Mitochondrial antibody was negative in both patients and when used in conjunction with the Kveim-Siltzbach skin test serves to differentiate chronic intrahepatic cholestasis secondary to sarcoidosis from primary biliary cirrhosis.
[11C]Docetaxel and Positron Emission Tomography for Noninvasive Measurements of Docetaxel Kinetics
Authors: Astrid A.M. van der Veldt, Adriaan A. Lammertsma, N. Harry Hendrikse
Journal: Clinical Cancer Research (2007)

To the Editor: We read with great interest the article by Bradshaw-Pierce and colleagues ([1][1]) reporting a physiologically based pharmacokinetic (PBPK) model for docetaxel. Because docetaxel is frequently used for the treatment of several cancers, more often, recently, in combination with other
Psychiatric Assessment of Aggressive Patients: A Violent Attack on a Resident
Authors: Daniel Antonius, Lara Fuchs, Farah Herbert, Joe Kwon, Joanna L. Fried, Paul R.S. Burton, Tara Straka, Ze'ev Levin, Eve Caligor, Dolores Malaspina
Journal: American Journal of Psychiatry (2010)

Aggressive patients often target psychiatrists and psychiatric residents, yet most clinicians are insufficiently trained in violence risk assessment and management. Consequently, many clinicians are reluctant to diagnose and treat aggressive and assaultive features in psychiatric patients and instead focus attention on other axis I mental disorders with proven pharmacological treatment in the hope that this approach will reduce the aggressive behavior. Unclear or nonexistent reporting policies or feelings of self-blame may impede clinicians from reporting assaults, thus limiting our knowledge of the impact of, and best response to, aggression in psychiatric patients. The authors pre­sent the case of a young adult inpatient with a long history of antisocial and assaultive behavior who struck and injured a psychiatric resident. With this case in mind, the authors discuss the diagnostic complexities related to violent patients, the importance of assessing violence risk when initially evaluating a patient, and the relevance of risk assessment for treatment considerations and future management. This report illustrates common deficiencies in the prevention of violence on inpatient psychiatric units and in the reporting and response to an assault, and has implications for residency and clinician training.