tbuckley/cabot-search huggingface dataset:
Abstract 1921: A novel FAK kinase inhibitor (PF-4554878) decreases growth and induces apoptosis in pancreatic neuroendocrine tumor cells
Authors: Rony Francois, Shun Lu, Di-Hua He, Maria Zajac-Kaye, Steven N. Hochwald
Journal: Cancer Research (2012)

Abstract Introduction: Pancreatic neuroendocrine tumors (PNETs) are poorly understood and there are few effective therapies. Focal adhesion kinase (FAK) is an important tyrosine kinase implicated in cell survival signaling and found to be overexpressed in many malignancies. Our hypotheses are that 1) FAK expression is upregulated, 2) that FAK plays an important role in PNET cell survival, and 3) that a novel ATP competitive kinase inhibitor of FAK demonstrates anti-neoplastic efficacy in PNET cells. Methods: By Western blot, the expression of FAK was determined in frozen human PNETs compared to normal human pancreas. The compound, PF-4554878 (Pfizer), has been shown to be an ATP competitive kinase inhibitor of FAK. The in-vitro effects of this compound on cell signaling, viability and apoptosis in human pancreatic neuroendocrine cells (BON-1 and QGP-1) were evaluated. Statistical analysis was performed via t-test with significance defined as p&amp;lt;0.05. Results: FAK was found to be overexpressed in PNETs compared to normal pancreas. PF-4554878 not only caused a decrease in PNET cell viability with an IC50 of 5 µM in human pancreatic neuroendocrine cell lines, but also caused a statistically significant dose-dependent increase in apoptosis by TUNEL staining and/or PARP cleavage. These effects were associated with a decrease in Y397 phosphorylation of FAK. Conclusions: A novel compound that inhibits the kinase activity of FAK results in decreased PNET proliferation and induction of apoptosis. These effects appear to be mediated through downregulation of p-FAK (Y397). This compound deserves further study as a novel treatment strategy in human PNETs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1921. doi:1538-7445.AM2012-1921
Osteopontin promotes vascular cell adhesion and spreading and is chemotactic for smooth muscle cells in vitro.
Authors: L Liaw, M Almeida, C E Hart, S M Schwartz, C M Giachelli
Journal: Circulation Research (1994)

Osteopontin is an Arg-Gly-Asp-containing acidic phosphoprotein recently shown to be upregulated in vascular smooth muscle during rat arterial neointima formation and in human atherosclerotic plaques. Functional studies showed that osteopontin promoted adhesion of both cultured aortic endothelial cells and aortic smooth muscle cells. Adhesion of vascular cells to osteopontin was dose dependent and half maximal when solutions containing 7 and 30 nmol/L osteopontin were used to coat wells for endothelial and smooth muscle cells, respectively. Smooth muscle cells adherent to osteopontin were spread after 60 minutes, whereas endothelial cells remained round, although flattened, at this time point but were spread at 90 minutes. Cell spreading on osteopontin was accompanied by the formation of focal adhesion plaques. A newly developed anti-osteopontin antibody completely inhibited adhesion of both cell types to osteopontin but not to fibronectin or vitronectin. In addition, the peptide GRGDSP blocked adhesion to osteopontin, suggesting that integrins mediate Arg-Gly-Asp-dependent adhesion. Indeed, an antibody against the alpha v beta 3 integrin neutralized adhesion of both endothelium and smooth muscle cells to osteopontin by approximately 50%, demonstrating that alpha v beta 3 is one osteopontin receptor on vascular cells. Osteopontin also promoted the migration of smooth muscle cells in a Boyden-type chamber, with half-maximal effects observed at 77 nmol/L osteopontin. Checkerboard analysis demonstrated that this stimulus was chemotactic in nature. Our findings suggest that osteopontin may be functionally important as an adhesive and chemotactic molecule for vascular cells, particularly when levels of osteopontin are dramatically increased, as is the case after arterial angioplasty and in atherosclerotic plaques.
Relationship of Sodium Reabsorption and Glomerular Filtration Rate to Renal Glucose Reabsorption
Authors: Neil A. Kurtzman, Martin G. White, Philip W. Rogers, James J. Flynn
Journal: Journal of Clinical Investigation (1972)

Glucose reabsorption was measured in dogs in which sodium reabsorption was stimulated by obstruction of the thoracic inferior vena cava or inhibited by volume expansion with Ringer's lactate. Glucose reabsorption was much higher during periods of enhanced sodium reabsorption than during sodium diuresis. The relationship of glucose reabsorption to glomerular filtration rate was examined using data from animals that had fractional sodium excretion rates of less than 1%. Under this condition the relationship of glucose reabsorption to glomerular filtration rate is highly linear. When points obtained during sodium diuresis (CNa/GFR>0.1) are plotted on the same graph, glucose reabsorption at any given glomerular filtration rate is much less than during antidiuresis. Glucose reabsorption divided by glomerular filtration rate varies inversely with fractional sodium excretion. This study demonstrates that glomerular tubular balance for glucose exists in the dog and that this balance is changed when sodium reabsorption changes.
CARDIOVASCULAR OUTCOMES IN WOMEN WITH AND WITHOUT PREECLAMPSIA/ECLAMPSIA: A 14 YEAR FOLLOW-UP STUDY
Authors: Mary Downes Gastrich, Sampada K. Gandhi, John Pantazopoulos, Edith Zang, Nora M. Cosgrove, Javier Cabrera, John B. Kostis
Journal: Journal of the American College of Cardiology (2012)
Steroid withdrawal in cyclosporin a (CSA)-treated liver transplant(LT) recipients. Pathological and biochemical assessment
Authors: C. Brigot, C. Duvoux, G. Pageaux, E.S. Zafrani, V. Coste, M. Bismuth, F. Roudot-Thoraval, D. Cherqui, J. Domergue, D. Larrey, D. Dhumeaux
Journal: Journal of Hepatology (2000)
THE TEACHING OF PHYSICAL THERAPY TO UNDERGRADUATE MEDICAL STUDENTS
Authors: IRVING S. CUTTER
Journal: JAMA (1934)

No matter how vigorously the medical profession may deny utilitarian objectives in medicine, the physician, after all, to his patients in general is a healer, and his duty to the individual who is ill involves the use and application of all therapeutic measures conducive to the restoration of that patient to health. Many graduates are handicapped because of inadequate emphasis on therapeutic resourcefulness. Too often the clinical teacher gives the impression that, if a correct diagnosis is made, the treatment is easy. The patient desires to get well; hence, in the practice of medicine, therapy requires attention at least equal to that devoted to diagnosis. There is, we believe, a growing consciousness on the part of the medical profession of the great value of the numerous procedures known as physical therapy. Realization of this has been aided by the establishment of the Council on Physical Therapy of the American Medical
No artifact, hepatitis E is emerging
Authors: Hans L. Zaaijer
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. To the Editor: Wenzel et al. report a declining hepatitis E virus (HEV) antibody (anti‐HEV) seroprevalence in 1,092 German sera obtained in 1996 and in 2011 and conclude that a recent increase of endemic hepatitis E is an artifact caused by increased awareness.1 We also reported a declining seroprevalence, testing 538 Dutch sera from 1988, 621 from 2000, and 5,239 from 2011; but, in addition, we show that, recently, anti‐HEV seroprevalence in young (largely unexposed) adults increased significantly.2 In addition, the routine screening for HEV RNA of Dutch blood donations, targeted for solvent‐detergent plasma production, in pools of 96, shows an increasing incidence. In the first 6 months of screening (October 2012–March 2013), 7 of 19,191 donations (1:2,742) were found to be confirmed HEV RNA positive. In the most recent 6 months (April 2014–September 2014), 18 of 10,991 (1:611) donations were found to be confirmed HEV RNA positive. Our data indicate that HEV has returned and that HEV infections are increasing in The Netherlands.
The World Health Organisation in Africa
Authors: F Godlee
Journal: BMJ (1994)

In September 1994, there will be a crucial vote in international public health: the nomination of the World Health Organization (WHO)'s next regional director for Africa. The appointment will affect how $850 million is spent and what happens to the health of 550 million of the world's poorest people. The current regional director, Dr Lobe Monekosso, took office 10 years ago, and just over half of the region's $136 million budget for 1992-3 reached the region's 45 member states. The rest of the budget was spent at the regional office in Zaire, along with 2/3 of the 112 million pounds sterling donated for the AIDS and immunization programs. Chronic difficulties caused by Africa's lack of infrastructure have been aggravated by civil unrest in Brazzaville, where the regional office is based, which prevented the WHO's auditors from evaluating biennial spending. The main contender for the post is Dr. Ebrahim Samba, director of the onchocerciasis control program, who took over the ailing program in 1980 and has turned it into a success. From its base in Ouagadougou in Burkina Faso, it has cut the prevalence of onchocerciasis as a public health problem in 11 West African countries from 95% in 1974 to less than 5%. The appointment will be decided by the regional committee, which is made up of health ministers of the region's 45 member states, and the incumbent has the upper hand. Regardless of the result of the regional committee meeting in Brazzaville, the time has come for a thorough review of the effectiveness of the WHO in Africa to reassure those treasury officials in donor countries waiting to withdraw their funds. The WHO needs to reform its selection procedures and make its regional directors more answerable to the World Health Assembly; in this way it will eliminate the existing potential for too much power combined with too little accountability.
Autologous x-irradiated tumour cells and percutaneous BCG in operable lung cancer.
Authors: B H Stack, N McSwan, J M Stirling, D J Hole, W G Spilg, I McHattie, J A Elliott, C R Gillis, M A Turner, R G White
Journal: Thorax (1982)

To determine the value of specific immunotherapy with adjuvant BCG in operable lung cancer, the immunological and clinical results of serial postoperative injections of autologous irradiated tumour cells and BCG were compared with those of a single preoperative injection of BCG in two randomly selected groups of patients undergoing resection of their tumours. There was a significant rise in tuberculin skin reactivity from seven weeks to 11 months after operation in the treated group. Actuarial curves for survival and freedom from tumour recurrence and median survival times showed an advantage for the treated patients who had stage I tumours, but these differences were significant only at the levels p = 0.07 - 0.09. Survival and duration of freedom from tumour recurrence was greater in autograft-treated patients whose skin responded to a weak test dose of dinitrochlorobenzene (DNCB) after sensitisation with 2% DNCB than in control DNCB-positive patients (p = 0.02). There were no significant differences in the actual proportion of patients from each group surviving at two years. The results show that this form of specific immunotherapy with adjuvant may have a beneficial effect in patients with stage I tumours and those who become sensitised to 2% DNCB after the first exposure.
Intrinsic Muscle Atrophy and Toe Deformity in the Diabetic Neuropathic Foot
Authors: Sicco A. Bus, Qing X. Yang, Jinghua H. Wang, Michael B. Smith, Roshna Wunderlich, Peter R. Cavanagh
Journal: Diabetes Care (2002)

OBJECTIVE—The objectives of this study were to compare intrinsic foot muscle cross-sectional area (CSA) in patients with diabetic polyneuropathy and nondiabetic control subjects and to examine the association between intrinsic muscle CSA and clawing/hammering of the toes in neuropathic feet. RESEARCH DESIGN AND METHODS—High-resolution T2-weighted fast spin-echo images and parametric T2 multiple spin-echo images were acquired using multiple spin-echo magnetic resonance imaging (MRI) of frontal plane sections of the metatarsal region of the foot in a sample of eight individuals with diabetic polyneuropathy and eight age- and sex-matched nonneuropathic nondiabetic control subjects. The configuration of joints of the second toe was obtained using a three-dimensional contact digitizer. RESULTS—Remarkable atrophy was found in all the intrinsic muscles of neuropathic subjects as compared with nondiabetic control subjects. Quantitative T2 analysis showed a 73% decrease in muscle tissue CSA distally in the neuropathic subjects. Muscle comprised only 8.3 ± 2.9% (means ± SD) of total foot CSA compared with 30.8 ± 3.9% in control subjects. No significant differences were found between the groups in the metatarso-phalangeal and proximal and distal interphalangeal joint angles of the second ray. Moreover, clawing/hammering of the toes was found in only two of eight neuropathic subjects. CONCLUSIONS—Although sensory neuropathy is often emphasized in considerations of diabetic foot pathology, our results show that the consequences of motor neuropathy in the feet are profound in people with diabetes. This has implications for foot function and may play a significant role in postural instability. However, intrinsic muscle atrophy does not necessarily appear to imply toe deformity.
Endemic bladder stones.
Authors: M Ashworth
Journal: BMJ (1990)

psychosocial consequences, They need to attend clinics and have regular blood tests.Furthermore, minor toxicity can affect the quality of life, particularly if the drug is to be taken for many years by those who would otherwise be well.Zidovudine is still the only antiviral drug available with proved efficacy in HIV disease, but the extension of its licence to asymptomatic disease does not make the decision of when to start treatment any easier for the doctor or the patient.A decision based solely on the results of a laboratory investiga- tion that is not universally available and whose biological and laboratory variability is considerable is clearly difficult.5The terms "repeated" and "rapidly falling" in relation to CD4+ cell counts are not defined clearly because the data are insufficient.The European and Australian trials in asympto- matic people must continue to answer fully the long term questions about efficacy and toxicity.Any move to intervene in asymptomatic infection and to prescribe low doses should be approached with, caution.
49 Association between HBeAg seroconversion and sustained HBV-DNA suppression in patients treated with peginterferon alpha-2a (40KD) (PEGASYS) for HBeAg-positive chronic hepatitis B (CHB)
Authors: T. Piratvisuth, G.K.K. Lau, P. Marcellin, W.C. Chow, G. Cooksley, M.W. Fried, S.W. Paik, Y.F. Liaw, M. Popescu, P. Button
Journal: Journal of Hepatology (2006)
Skin Lesions and Deafness in Disseminated Tuberculosis
Authors: A. W. Lees, I. B. Munro
Journal: BMJ (1954)

DEAFNESS IN HYPERPARATHYROIDISM MEDICALISIORNALThe evidence cited cannot be regarded as conclusive, as the cases were all seen after recovery from deafness, but it is highly suggestive of a close relationship between rever- sible deafness, aphonia, muscular weakness, increased nerve accommodation, and hypercalcaemia.It is perhaps rele- vant to note that other causes of "chemical deafness" are quinine, which is well known to block nerve conduction (Cooper, 1924).and analgesics such as salicylates and acetanilid (Macht, Greenberg, and Isaacs, 1919).The latter drug at least has been shown to depress muscle-nerve excit- ability (Macht, 1919).Hyperparathyroidism is rare and is usually diagnosed at orthopaedic clinics.It is hoped that this paper will stimulate interest so that the occurrence of deafness can be fully investigated before and after operation. SummaryDisturbances of hearing are reported in five cases of hyperparathyroidism, and aphonia in one case.In three cases these symptoms disappeared after removal of a parathyroid adenoma, and examination showed no defect of hearing.Increased nerve accommodation, demonstrated in one case, is suggested as a possible cause of these symptoms.The cases are reported so as to draw attention to an unusual cause of nerve deafness.
STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT
Authors: Louise Pearce, Albert E. Casey
Journal: The Journal of Experimental Medicine (1930)

Consecutive weekly observations on the total white cell count of the peripheral blood were made on 5 groups of normal rabbits, a total of 45 animals, during a period of 20 months from October, 1927 to July, 1929. The duration of individual group examinations varied from 8 to 35 weeks. In the case of 4 groups followed 13 to 35 weeks, the general trend of the total white cell means was toward increasing values; with the group followed 8 weeks, the means were maintained at a constant level. The changes in the levels of the granular cell means were usually accompanied by changes in a similar direction of the non-granular cell means. In the case of 3 of the 4 groups followed for the longest periods, the greatest relative alterations occurred in the non-granular cells. The fluctuations in the mean values of the total white cells and of the granular and the non-granular cells which were observed in one group of rabbits, were also generally observed in another group examined during the same months. The period of greatest irregularity in the mean values of the total white cell means and of the granular and the non-granular cell means as well, occurred during the late winter and spring months of both years. The general level of the total white cell mean values in the groups examined during 1927-28 was higher than that of the groups observed during 1928-29. A similar difference was found in the granular and non-granular mean values but it was somewhat less marked in the case of the granular cells.
A Double-Masked Placebo-Controlled Trial Assessing Effects of Various Doses of BTS 67,582, a Novel Insulinotropic Agent, on Fasting Hyperglycemia in NIDDM Patients
Authors: Carmela A Skillman, Philip Raskin
Journal: Diabetes Care (1997)

OBJECTIVE To determine the effect over a 4-week period of varying doses of BTS 67,582, a novel nonsulfonylurea insulinotropic agent, on fasting plasma glucose (FPG) levels in sulfonylurea-responsive NIDDM patients. RESEARCH DESIGN AND METHODS This was a 12-week multicenter, double-masked, placebo-controlled trial. Patients entered a 4-week stabilization period during which they received their previously prescribed sulfonylurea. Qualified patients (FPG ≤ 10 mmol/l) then entered a 4-week sulfonylurea withdrawal single-masked placebo run-in period. Qualified patients (FPG 8.9–16.7 mmol/l) were randomized to either placebo (n = 14), 50 mg b.i.d. BTS 67,582 (n = 18), 250 mg b.i.d. BTS 67,582 (n = 18), 500 mg b.i.d. BTS 67,582 (n = 15), 100 mg q.d. BTS 67,582 (n = 17), or 500 mg q.d. BTS 67,582 (n = 16). The primary efficacy variables were mean changes from baseline in FPG and fructosamine (FRUC). Additional variables included mean changes from baseline in HbA1c, fasting serum insulin (FSI), and fasting serum C-peptide. RESULTS After 4 weeks of treatment, all BTS 67,582 dose groups showed a decrease from baseline in FPG and FRUC compared with the placebo group. The treatment groups of 250 mg b.i.d. (−3.1 ± 0.7 mmol/l), 500 mg b.i.d. (−2.3 ± 0.6 mmol/l), and 500 mg q.d. (−1.2 ± 0.7 mmol/l) had statistically significant (P &amp;lt; 0.05) decreases in FPG compared with placebo (0.7 ± 0.6 mmol/l). Similarly, there were statistically significant (P &amp;lt; 0.05) decreases from baseline in FRUC for the 250 mg b.i.d (−55 ± 10 μumol/l), 500 mg b.i.d. (−40 ± 12 μumol/l), and 500 mg q.d. (−13 ± 9 μumol/l) treatment groups compared with placebo (15 ± 11 μumol/l). Although the treatment period was only 4 weeks in duration, there were also significant differences (P &amp;lt; 0.05) in the HbA1c changes from baseline for the 250 mg b.i.d. (0.0 ± 0.1%) and 500 mg b.i.d. (−0.2 ± 0.1%) treatment groups compared with placebo (0.6 ± 0.2%). There were no significant differences among the treatment groups in the changes from baseline for FSI or C-peptide levels. The most frequently reported side effects were headache, asthenia, infection, and thirst, and the incidence of these events as well as the incidence of study drug discontinuation was comparable in all treatment groups including placebo. CONCLUSIONS Four weeks of treatment with BTS 67,582 at doses of 250 mg b.i.d. and 500 mg b.i.d. in NIDDM patients was effective in reducing FPG and FRUC, with significant results also seen for HbA1c. The drug was well tolerated with an incidence of discontinuations and laboratory side-effect safety profiles comparable to placebo. BTS 67,582 is a safe and effective oral treatment for NIDDM patients.
Prevention and reversal of adoptively transferred, chronic relapsing experimental autoimmune encephalomyelitis with a single high dose cytoreductive treatment followed by syngeneic bone marrow transplantation.
Authors: D M Karussis, U Vourka-Karussis, D Lehmann, H Ovadia, R Mizrachi-Koll, A Ben-Nun, O Abramsky, S Slavin
Journal: Journal of Clinical Investigation (1993)

A chronic relapsing form of experimental autoimmune encephalomyelitis (CR-EAE) was induced in SJL/J mice by adoptive transfer of lymph node cells (LNC) sensitized to guinea pig myelin basic protein (GMBP). We examined the efficacy of high dose immunosuppressive regimens (cyclophosphamide [CY] 300 mg/kg or total body irradiation [TBI] 900 cGy) followed by syngeneic bone marrow transplantation (SBMT) in prevention and treatment of already established CR-EAE. Treatment with TBI and SBMT on day 5 after the induction of CR-EAE, just before the onset of clinical signs, completely inhibited the appearance of the paralytic signs. The same treatment, applied 4 d after the clinical onset of the disease, led to a significant regression of the paralytic signs and to a total inhibition of spontaneous relapses during a follow-up period of 2 mo. Challenge of mice with GMBP+CFA 78 d after the passive induction of CR-EAE induced a relapse of the disease 7 d later in almost all of the untreated mice; in contrast, the same challenge given to TBI+SBMT-treated mice caused a delayed relapse (30 d later) in only a minority (3/7) of the challenged mice. In vitro lymphocytic proliferative responses to GMBP and purified protein derivative were significantly lower in TBI/SBMT-treated mice before and after the GMBP challenge, although these mice were fully immunocompetent, as evidenced by their normal lymphocytic proliferation to concanavalin A (ConA) and the FACS analysis of their lymphocytic subpopulations. A similar beneficial therapeutic effect was observed in mice treated with CY followed by SBMT, after the onset of CR-EAE. Our results could support possible clinical applications of similar therapeutic strategies, involving acute immunosuppression followed by stem cell transplantation and retolerization of the reconstituting immune cells in life-threatening neurological and multisystemic autoimmune diseases.
Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9N2) vaccine in healthy adults: phase I randomised trial
Authors: Iain Stephenson, Karl G Nicholson, Reinhardt Glück, Robert Mischler, Robert W Newman, Abraham M Palache, Neville Q Verlander, Fiona Warburton, John M Wood, Maria C Zambon
Journal: The Lancet (2003)