tbuckley/cabot-search huggingface dataset:
Phosphatidylinositol 3′-Kinase Activation Leads to Multidrug Resistance Protein-1 Expression and Subsequent Chemoresistance in Advanced Prostate Cancer Cells
Authors: John T. Lee, Linda S. Steelman, James A. McCubrey
Journal: Cancer Research (2004)

Abstract The development of androgen-independent growth in advanced carcinoma of the prostate (CaP) is associated with poor prognosis and few therapeutic options. Chemotherapeutic drugs offer the afflicted patient palliative benefits, but these are short-lived because of the chemoresistant nature of hormone-refractory prostate cancer. Given the high percentage of CaP patients with mutations in the PTEN tumor suppressor gene, we sought to determine the involvement of the phosphatidylinositol 3′-kinase (PI3K) cascade in the development of CaP drug resistance. PTEN-negative PC3 cells were observed to have increased resistance to both doxorubicin and paclitaxel when compared with PTEN-positive DU145 cells. Furthermore, modulation of PI3K activity with the use of constitutively active and dominant-negative inhibitors was found to affect the ability to CaP cells to respond to chemotoxic treatments. Additionally, inhibition of PI3K with a small molecular weight inhibitor (LY294002) was able to potentiate the antineoplastic activity of both doxorubicin and paclitaxel in CaP cells. Interestingly, multidrug resistance protein-1 (MRP-1) expression, but not MDR-1 (p-glycoprotein), was observed to be induced as a consequence of PI3K activation in these cell types. Inhibition of MRP-1 expression via siRNA was observed to synergistically sensitize CaP cells to chemotoxic drugs while having no appreciable effect on cell growth in the absence of these compounds. Taken together, these data suggest that PI3K activation can lead to the development of chemoresistant cells in prostatic carcinomas through the up-regulation of MRP-1. Thus, inhibition of PI3K activity with concomitant administration of chemotoxic compounds may prove beneficial in preventing the development of drug resistance in patients with hormone-refractory prostate cancer.
BI-31 * ANALYSIS AND QUANTIFICATION OF MULTIPLE ANTIGEN EXPRESSION IN GLIOBLASTOMA
Authors: L. Weng, Y. Zhai, M. D'Apuzzo, B. Badie, S. J. Forman, M. Barish, C. E. Brown
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM), one of the most common and fatal types of brain tumor, is marked by significant antigenic heterogeneity. Identification and quantification of tumor related antigens in the context of GBM tissue is an essential step towards developing antigen- targeted therapies. Immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) clinical specimens is a valuable technique for evaluating antigen expression in large study cohorts. To overcome the limitations of manual semi-quantitative scoring and subjectivity in the evaluation of IHC staining, we analyzed and quantified multiple antigens across entire tumor sections using Image Pro Premier v9.1 (DAB plug-in). For each slide, dense tumor regions (DTRs, tumor cells >60%), tumor infiltration regions (TIRs, tumor cells <50%) and pseudopalisading necrosis regions (PPNs) were defined from HE section by a neuropathologist. We quantified the expression of tumor-associated antigens IL13Rα2, HER2, EGFR and the proliferation marker Ki67 within these defined regions for 44 brain tumor samples (35 stage IV and 9 stage III). Our results demonstrate the heterogeneous expression patterns of IL13Rα2, HER2 and EGFR in GBMs. For example, in dense tumor regions 52%, 61% and 77% of samples showed IL13Rα2, HER2 or EGFR positivity, respectively. In correlation studies, 25% of samples were triple positive, 11% of samples showed double positivity for IL13Rα2 and HER2 or IL13Rα2 and EGFR, and 25% of samples were double positive of EGFR and HER2. Less than 7% of samples were negative for all three antigens. Interestingly, a higher percentage of samples showed triple positive expression in PPN regions (43%) versus the DTR (25%) and TIR (25%) regions. Also, Ki67 positivity was higher in PPN and DTR regions. In this study we developed methods for combining pathological annotations with DAB-capturing software, which allowed us to quantify protein expression in a more precise, consistent and efficient manner.
Abstract P1-13-13: Association between the serum concentrations of tamoxifen and its metabolites and age during steady state breast cancer treatment
Authors: E Lien, H Søiland, S Lundgren, T Ås, VM Steen, G Mellgren, J Gjerde
Journal: Cancer Research (2013)

Abstract It has been suggested that the concentrations of tamoxifen and its demethylated metabolites increase with age. Here, we measured the serum concentrations of the active tamoxifen metabolites, 4OHtamoxifen (4OHtam), 4OHNdesmethyltamoxifen (4OHNDtam, Endoxifen), tamoxifen and its demethylated metabolites. Their relations to age were examined. 151 breast estrogen receptor and/or progesterone receptor positive cancer patients were included. Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Their serum concentrations were related to the age of the patients. The concentrations of 4OHNDtam, tamoxifen, NDtam (N-desmethyltamoxifen), and NDDtam (N-desdimethyltamoxifen) were positively correlated to age (n = 151, P = 0.017, 0.045, 0.011, and 0.001 respectively). Up to tenfold inter-patient variation in the serum concentrations was observed. The median (inter-patient range) of the concentrations 4OHNDtam in the age groups 30-49, 50-69 and &amp;gt;69 years were 44 (65) ng/ml, 51 (116) ng/ml, and 54 (159) ng/ml, respectively. We conclude that the serum concentrations of 4OHNDtam (endoxifen), tamoxifen and its demethylated metabolites increase with age during steady state tamoxifen treatment. The observed high inter-patient range in serum concentrations of tamoxifen and its metabolites, especially in the highest age group, suggest that use of therapeutic monitoring of tamoxifen and its metabolites is warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-13.
REMOVAL OF SKIN SUTURES
Authors: Robert H. Ivy
Journal: JAMA (1953)

<h3>To the Editor:—</h3> InThe Journalfor July 25, 1953, page 1231, Weinstein and Roberts describe an easy method of removal of skin sutures. A practically identical method was described by A. P. Hovnanian in<i>Plastic and Reconstructive Surgery</i>(<b>8</b>:407 [Nov.] 1951). I have used this method myself during the past year and a half and find it very satisfactory.
COMMUNITY PSYCHIATRY, SOCIAL PSYCHIATRY, AND COMMUNITY MENTAL HEALTH WORK: SOME INTER-PROFESSIONAL RELATIONSHIPS IN PSYCHIATRY AND SOCIAL WORK
Authors: PORTIA BELL HUME
Journal: American Journal of Psychiatry (1964)

In community mental health work, the psychiatrist is primarily a clinician with public health responsibilities, that is, a new kind of practitioner with consultative, administrative and research functions. By the same token the psychiatric social worker is potentially, by training and experience, a clinician with public welfare responsibilities in community psychiatry and other mental health work, a practitioner with the available professional skills of a community organization specialist, a public welfare administrator, a groupworker, a supervisor, a consultant-educator, and a researcher. Acceptance of new responsibilities and roles is indicated by the highly motivated trainees from both professions, who are now seeking postgraduate, special training in community psychiatry. At the Center for Training in Community Psychiatry at Berkeley during the past two and a half years, for example, 176 psychiatrists and 124 psychiatric social workers have been enrolled together in 9 different courses. Social workers are likewise members of the faculty. Such inter-professional relationships in teaching and learning have, as a matter of fact, enhanced both the theory and practice of community psychiatry, and promoted the educational process in what must still be considered a pioneering area of psychiatry.
Recurrent Left Atrial Myxoma
Authors: OM P. BAHL, G. CHARLES OLIVER, THOMAS B. FERGUSON, NIKOLAUS SCHAD, BRENT M. PARKER
Journal: Circulation (1969)

Recurrence of a left atrial myxoma 6 years after the initial resection is reported. This, to our knowledge, is the second such case, and it emphasizes the need for a complete resection of the underlying atrial septum or atrial wall in cases of myxoma.
Decreased growth inhibition by recombinant gamma interferon is associated with increased transforming growth factor-α production in keratinocytes cultured from psoriatic lesions
Authors: B.J. NICKOLOFF, R.S. MITRA, J.T. ELDER, G.J. FISHER, J.J. VOORHEES
Journal: British Journal of Dermatology (1989)

Journal Article Decreased growth inhibition by recombinant gamma interferon is associated with increased transforming growth factor‐α production in keratinocytes cultured from psoriatic lesions Get access B.J. NICKOLOFF, B.J. NICKOLOFF Departments of Pathology University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A. B.J.Nickoloff, Department of Pathology, M4232 Medical Science 1, 1301 Catherine Road, Ann Arbor, MI 48109‐0602, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar R.S. MITRA, R.S. MITRA Departments of Pathology University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J.T. ELDER, J.T. ELDER Dermatology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar G.J. FISHER, G.J. FISHER Dermatology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J.J. VOORHEES J.J. VOORHEES Dermatology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 121, Issue 2, 1 August 1989, Pages 161–174, https://doi.org/10.1111/j.1365-2133.1989.tb01795.x Published: 01 August 1989
Easing the spring
Authors: Fiona Godlee
Journal: BMJ (2007)

As the Northern hemisphere's daffodils do their thing, presaging the spring, the BMJ carries, as well as a daffodil on the cover, some good news. It is possible to improve children's antisocial behaviour by teaching their parents positive parenting skills. Not only that, but the intervention is cost effective.

Conduct disorder is the commonest reason for referring children and adolescents to mental health services, and antisocial behaviour in childhood is a powerful predictor of public service use in adulthood ( BMJ 2001;323:191; doi: 10.1136/bmj.323.7306.191). Last year we published the results of an evaluation of Sure Start in England ( BMJ 2006;332:1476; doi: 10.1136/bmj.38853.451748.2F …
Potentiation of Evoked Vesicle Turnover at Individually Resolved Synaptic Boutons
Authors: Timothy A Ryan, Noam E Ziv, Stephen J Smith
Journal: Neuron (1996)

We have studied synaptic plasticity in hippocampal cell cultures using a new imaging approach that allows unambiguous discrimination of presynaptic function at the level of single synaptic boutons. Employing a protocol designed to test for use-dependent plasticity resembling N-methyl-D-aspartate receptor-dependent long-term potentiation (NMDA-type LTP), we find that brief tetanic stimuli induce a potentiation of evoked synaptic vesicle turnover that lasts for at least 1 hr. Induction of this clearly presynaptic potentiation is blocked by putative postsynaptic glutamate receptor antagonists, suggesting that a retrograde induction signal might be involved. Potentiation appears to occur approximately equally at boutons of low and high initial release probabilities, and evidently does not involve an increase in the size of the total recycling synaptic vesicle pool.
Friend to the brain, foe to the spine
Authors: Amy Maxmen
Journal: The Journal of Experimental Medicine (2008)

Shouting during a World Cup match and shouting during a funeral will be met with different reactions. Context is equally important in a cytokine outburst, find Lees et al. on page 2633. Regional responses to interferon-γ (IFNγ) dictated whether the spinal cord or cerebellum came under fire in mice with EAE, a mouse model of human multiple sclerosis (MS). In other words, both outburst and audience matter.






Figure 1

Inflammation (arrows) is focused on the cerebellum, not the spine, in mice lacking the IFNγ receptor.




IFNγ, the signature T helper (Th)-1 cytokine, contributes to CNS inflammation during EAE. But not all forms of EAE are alike. In classical EAE, the T cell attack is focused on the spinal cord. But in atypical disease, the cerebellum and brain stem are the primary victims. A prior study suggested that the ratio of interleukin (IL)-17 to IFNγ determines whether disease pathology occurs in the spine or brain, with increasing levels of IL-17 associated with disease in the brain. But the data from Lees et al. instead show that lesion location is mainly controlled by the brain's response to IFNγ.

When transferred into wild-type mice, the authors show, myelin-specific Th1 cells attacked the spinal cord. But when transferred into mice lacking the IFNγ receptor, the cells instead attacked the cerebellum and brain stem, sparing the spinal cord. The production of IL-17 by the transferred T cells was comparable in both settings. However, the production of IL-17 by non-T cells predominated in the cerebellum, suggesting that IL-17–producing cells contribute to atypical disease but do not determine its location.

In agreement with past reports, however, transferring mixed populations of IFNγ- and IL-17–producing cells resulted in a mixed disease phenotype, with increasing numbers of IFNγ producers causing progressively more spinal cord disease.

Why IFNγ induces inflammation in one tissue and not another remains unknown—particularly because no obvious regional differences in the expression of the receptor were detected. The authors suspect that IFNγ triggers a localized production of T cell–attracting chemokines in the spine.
Increases in plasma oncotic pressure during acute cardiogenic pulmonary edema.
Authors: J Figueras, M H Weil
Journal: Circulation (1977)

Colloid osmotic pressure (COP) was measured in 95 patients with clinical and radiological evidence of acute cardiogenic pulmonary edema. Fifty patients who were admitted for coronary observation but in whom acute myocardial infarctin was excluded, and 21 patients who had sustained acute myocardial infarction without evidence of left ventricular failure served as controls. Significantly higher values of COP, total plasma protein, and hematocrit were observed in patients with pulmonary edema. Increases in COP during pulmonary edema were best explained by transudation of hypooncotic fluid into extravascular spaces. Following treatment of pulmonary edema in 76 patients with furosemide, morphine, and oxygen, pulmonary edema was reversed in 65 patients. Reabsorption of hypooncotic fluid from extravascular sites with a significant decline in COP, total protein and hematocrit followed reversal of pulmonary edema. No significant changes in these parameters were observed in patients who failed to respond to therapy. These observations implicate filtration of hypooncotic fluid from the intravascular compartment during onset of cardiogenic pulmonary edema and reabsorption of hypooncotic fluid into the intravascular compartment during reversal of pulmonary edema.
STUDIES ON INFLUENZA VIRUS
Authors: Edwin H. Lennette, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1941)

Influenza complement fixation tests designed for use with ferret serum are described. Complement-fixing antigens derived from influenza ferret lungs were unsatisfactory due to their low content of soluble antigen; those prepared from mouse lungs or developing chick embryo membranes proved to be better antigenically and were reliable when the various reagents in the test were properly adjusted to eliminate non-specific fixation of complement. The results of cross complement fixation tests indicated that the soluble antigens of the PR8 and W.S. strains of influenza A virus were closely similar, if not identical. They indicated also that the soluble antigen of swine virus possessed components present in the antigens of the human strains of virus.
Structure and behaviour in hydrophilic matrix sustained release dosage forms: 2. NMR-imaging studies of dimensional changes in the gel layer and core of HPMC tablets undergoing hydration
Authors: A.R. Rajabi-Siahboomi, R.W. Bowtell, P. Mansfield, A. Henderson, M.C. Davies, C.D. Melia
Journal: Journal of Controlled Release (1994)
Managing impotence in diabetes. Wait to be asked before offering advice.
Authors: W Alexander
Journal: BMJ (1993)

Two drugs are better than one EDITOR,-We disagree with some of D E Price's views on managing erectile dysfunction in diabetes.'The erectile dysfunction is not always organic in origin since psychogenic factors based on anxiety are as common in diabetic patients as in the general population.A total lack of erections under all circumstances, including during sleep and on waking, may indeed be due to neurogenic impotence, but patients with this are a minority.Patients more commonly complain of a partial erection during sexual activity, which suggests a vasculogenic rather than a neurogenic cause.Intracavernous injection of a vasoactive agent is a simple means of distinguishing vasculogenic from psychogenic and neurogenic impotence.More sophisticated investigations are rarely neces- sary except to investigate the possibility of occult neurological problems or of arterial disease worth treating surgically-that is, in young non-smoking men under 40 who do not have diabetes or hypertension.The use of intracavernous agents for erectile dysfunction has indeed revolutionised the management of this problem, but, at least in theory, papaverine should not now be used alone because of the occurrence of penile fibrosis and priapism.The incidence of these complications is diminished by the addition of phentolamine, but prostaglandin E1 is safer, although a suitable formulation for general use is not yet available.
Prevention of Tuberculosis Among Tuberculin Reactors: Maximizing Benefits, Minimizing Risks
Authors: George W. Comstock
Journal: JAMA (1986)

Although an ounce of prevention may often be worth a pound of cure, there is an inherent and unfortunate tendency for prevention to be discouraging. Only in the midst of an epidemic are preventive efforts likely to be visible and dramatic. In most situations, something that is prevented is a nonevent. Individuals can hardly be expected to be aware of nonevents: these can be detected only by statistics. As a consequence, the benefits of prevention are more likely to appeal to our intellect than to our emotions. Bad effects, on the other hand, are usually readily recognized. Because they are likely to occur in close temporal association with the preventive procedure, they are perceived as resulting from that procedure even when they are merely coincidental. Their emotional effects can be severe, the more so because something bad happened when good was expected. Prevention of tuberculosis by giving isoniazid to persons
Results of surgery for atrial septal defect in patients of 40 years and over
Authors: M. Knight, S. Lennox
Journal: Thorax (1972)

Surgical closure of an atrial septal defect was performed on 104 patients over the age of 40 at the Brompton Hospital. The hospital mortality was 9·6%, reducing to 2·7% in the last six years. There were five late deaths. A moderate increase in preoperative pulmonary artery systolic pressure did not influence mortality. Twenty-five per cent of patients in preoperative atrial fibrillation have been maintained in sinus rhythm an average of five years following operation. Seven per cent of patients in sinus rhythm preoperatively left hospital in atrial fibrillation. Another 7% developed atrial fibrillation an average of seven years after operation. At late follow-up 75 patients were symptom-free and leading normal lives. It is concluded that patients in this age group with atrial septal defect benefit from surgical closure of the defect.
Management of Patients With Atrial Fibrillation (Compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS Recommendations)
Authors: Jeffrey L. Anderson, Jonathan L. Halperin, Nancy M. Albert, Biykem Bozkurt, Ralph G. Brindis, Lesley H. Curtis, David DeMets, Robert A. Guyton, Judith S. Hochman, Richard J. Kovacs, E. Magnus Ohman, Susan J. Pressler, Frank W. Sellke, Win-Kuang Shen
Journal: Journal of the American College of Cardiology (2013)
Power and the Profession of Obstetrics
Authors: T. Keith Edwards
Journal: JAMA (1983)

As a physician who has practiced  for 30 years,  approached this book with some apprehension. The very title caused me misgivings, and  was prepared not to like it. However,  found Mr Arney to have an excellent grasp of the history of our profession. In addition, he recognizes the schizophrenia in which the practice of  lives today, with our concern for natural childbirth on one hand and high-technology monitoring on the other. The author makes a special effort to avoid bias. He states, I try to avoid speaking either for  or for women as  outline my understanding of the history of obstetrics (p 13). Mr Arney adhered to this intention well.  After introducing the history of obstetrics, Mr Arney notes some of the jockeying for power that occurred among midwives, general practitioners, and obstetric specialists. These battles resulted in obstetric specialists being fully in
Utilization of α-Keto and α-Hydroxy Analogues of Valine by the Growing Rat
Authors: Rajender K. Chawla, Daniel Rudman
Journal: Journal of Clinical Investigation (1974)

When 70-80-g male albino rats eat a diet furnishing daily requirement of valine for optimal growth (70 mumol/g) and all other nutrients ("complete diet"), they gain weight at an average rate of 3.0 g/100 g body wt/day. When valine is removed, they lose weight at an average 2.1 g/100 g body wt/day. The growth retardation is improved or corrected by adding valine to the diet, daily weight gain being proportional to dietary valine content over a range of 0-70 mumol/g. Addition of alpha-ketoisovaleric acid instead of valine to the valine-free diet also improves or corrects the growth failure. Percent efficiency of alpha-ketoisovaleric acid as a substitute for valine was calculated as: 100 x (micromole valine per gram diet required to produce specified growth response)/(micromole alpha-ketoisovaleric acid per gram diet required to produce the same response). Efficiency of the substitution is inversely related to dietary content of the keto analogue, being 80% when diet contains 17.5 mumol/g (molar equivalent of (1/4) the daily requirement of valine), and 37% when diet provides 140 mumol/g (molar equivalent of twice the daily requirement of valine).alpha-Hydroxyisovaleric acid also substitutes for valine. Efficiency of the substitution at the single ration tested, 70 mumol/g diet, is 45%, similar to that for the keto analogue under the same conditions. When [1-(14)C]alpha-ketoisovaleric acid is injected intravenously, 30-80% of the administered radioactivity is exhaled as (14)CO(2) within 24 h. This finding suggests that inefficiency of alpha-ketoisovaleric acid as a substitute for valine results in part from degradation of the keto acid to isobutyric acid by branched chain dehydrogenase-decarboxylase. Oral administration of neomycin, polymyxin, and bacitracin reduces efficiency of alpha-ketoisovaleric acid as a substitute for valine by (1/4)-(1/2). This effect suggests that transamination of the keto acid may be performed in part by gastrointestinal microbes.