tbuckley/cabot-search huggingface dataset:
SB 242784, a Selective Inhibitor of the Osteoclastic V-H <sup>+</sup> -ATPase, Inhibits Arterial Calcification in the Rat
Authors: Paul A. Price, Helen H. June, Jessica R. Buckley, Matthew K. Williamson
Journal: Circulation Research (2002)

The present experiments were carried out to further test the hypothesis that arterial calcification is linked to bone resorption by determining whether the selective inhibition of bone resorption with SB 242784, a specific inhibitor of the osteoclastic V-H+-ATPase, will inhibit arterial calcification. Treatment for 96 hours with toxic doses of vitamin D caused widespread calcification in the aorta and in the femoral, mesenteric, hepatic, renal, and carotid arteries, and treatment with SB 242784 completely prevented the vitamin D-induced calcification of each of these arteries at a dose of 40 mg/kg per day and significantly reduced calcification at a dose of 10 mg/kg per day. Treatment with vitamin D also caused extensive calcification in the lungs, tracheal cartilage, and kidneys, and treatment with SB 242784 prevented or reduced calcification at each of these sites. Measurement of serum levels of cross-linked N-telopeptides, a specific measure of bone resorption activity, showed that treatment with vitamin D alone produced the expected 2.4-fold increase in bone resorption activity and that concurrent treatment with the 40-mg dose of SB 242784 reduced bone resorption activity to below control levels. With the inclusion of the present results, there are now three types of bone resorption inhibitors (each with an entirely different mode of action on the osteoclast) that share the ability to potently inhibit arterial calcification in the rat, the V-H+-ATPase inhibitor SB 242784, the cytokine osteoprotegerin, and the amino bisphosphonates alendronate and ibandronate.
Explaining Differences in Attitude Toward Adjuvant Chemotherapy Between Experienced and Inexperienced Breast Cancer Patients
Authors: S.J.T. Jansen, W. Otten, M.C.M. Baas-Thijssen, C.J.H. van de Velde, J.W.R. Nortier, A.M. Stiggelbout
Journal: Journal of Clinical Oncology (2005)

Previous studies have shown that patients who have experienced adjuvant chemotherapy (experienced patients) have a more favorable attitude towards chemotherapy than those who have not (inexperienced patients). However, not much is known about the reasons underlying this difference. According to the Theory of Planned Behavior, the attitude towards a particular behavior (eg, accepting chemotherapy) is based on beliefs about the likelihood of outcomes of the behavior and the evaluations of these outcomes. We used this theory to explore in what way the beliefs of experienced patients differed from those of inexperienced patients.A cross-sectional survey was undertaken among 719 patients who had been treated for early-stage breast cancer between 1998 and 2003. Patients were asked, first, to indicate the likelihood of six positive and six negative outcomes of undergoing chemotherapy and, second, to give their evaluation of these outcomes.Four hundred forty-six women filled in the questionnaire (response rate, 62%). As hypothesized, experienced patients (ie, patients who had been treated with adjuvant chemotherapy as part of their primary treatment plan) had a more positive attitude towards chemotherapy. Experienced patients provided higher likelihood estimates of treatment advantages, such as life prolongation. In addition, they evaluated the positive outcomes of chemotherapy more favorably. With regard to the negative outcomes of chemotherapy, few differences were observed between treatment groups.Experienced patients have more confidence in the positive outcomes of chemotherapy than inexperienced patients. This might be the result of a cognitive mechanism to justify the way in which patients were treated.
Survival in Patients With Type 2 Diabetes in a Swedish Community
Authors: Carl Johan Östgren, Ulf Lindblad, Arne Melander, Lennart Råstam
Journal: Diabetes Care (2002)

OBJECTIVE—To explore risk factors for all-cause mortality in patients with type 2 diabetes treated in primary care. RESEARCH DESIGN AND METHODS—A prospective population-based study of 400 patients with type 2 diabetes who consecutively completed an annual checkup in primary care in Skara, Sweden, during 1992–1993. Vital status was ascertained to year 2000. Baseline characteristics as predictors for mortality were analyzed by Cox regression and expressed as relative risks (RRs), with 95% CIs. RESULTS—During a mean follow-up time of 5.9 years, 131 patients died (56 deaths per 1,000 patients per year). In both sexes, all-cause mortality was predicted by HbA1c (by 1%; RR 1.14, 95% CI 1.01–1.27), and by LDL-to-HDL cholesterol ratios (1.15, 1.00–1.32). Increased mortality was also seen with prevalent hypertension (1.72, 1.21–2.44), microalbuminuria (1.87, 1.27–2.76), and previous cardiovascular disease (1.70, 1.15–2.50). Subanalyses revealed that increased mortality related to HbA1c was restricted to hypertensive patients with type 2 diabetes (1.23, 1.04–1.47). Serum triglycerides (by 1 mmol/l) predicted all-cause mortality in women (1.25, 1.06–1.47). CONCLUSIONS—Poor glucose and lipid control and hypertension predicted all-cause mortality. Survival was also predicted by prevalent microalbuminuria and by previous cardiovascular disease. Confirming results from clinical trials, this population-based study has implications for primary and secondary prevention.
Abstract #4435: Dephosphorylation of Rb by inhibition of cdk activity or upregulation of PP1 leads to Rb cleavage and apoptosis
Authors: Gabriel De Leon, Margaret Cavino, Mikilyn D'Angelo, Nancy Krucher
Journal: Cancer Research (2009)

The function of the Rb tumor suppressor in restricting proliferation is regulated by cell cycle dependent phosphorylation. In addition, it has been shown that Rb plays a protective role against apoptosis. Our work focuses on the regulation of Rb phosphorylation with respect to its function in apoptosis. Our previous studies have shown that siRNA mediated knockdown of Phosphatase Nuclear Targeting Subunit (PNUTS) leads to Protein Phosphatase 1 (PP1) activation toward Rb, Rb dephosphorylation and apoptosis in several cancer cell types. The apoptosis induced by PNUTS knockdown is dependent on Rb expression and occurs only in transformed cells and not in nontransformed cells. In addition, the ability of PNUTS siRNA to cause apoptosis is independent of p53 activation. In this study we analyzed the effect of combining cdk inhibition with the activation of PP1 using PNUTS knockdown. We have found that PNUTS knockdown significantly increases the apoptotic effects of the clinically relevant cdk inhibitor Roscovitine on HCT116 colon cancer cells and MCF7 breast cancer cells. The mechanism by which Roscovitine and PNUTS knockdown cause apoptosis appear to be similar in some aspects but not others. For example, both these treatments require expression of E2F1 to induce apoptosis. In addition, cleavage of the carboxy terminus of Rb is required for Roscovitine and PNUTS knockdown to stimulate apoptosis. However, a different subset of Rb phosphorylation sites are targeted by Roscovitine or PNUTS knockdown. Thus this data shows the importance of Rb phosphorylation in its function in apoptosis.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4435.
Myocyte hypertrophy in neonatal rat heart cultures and its regulation by serum and by catecholamines.
Authors: P Simpson, A McGrath, S Savion
Journal: Circulation Research (1982)

The role of hormones and other humoral factors in the regulation of myocardial hypertrophy has been difficult to evaluate. We asked whether myocardial cell hypertrophy could be demonstrated in cultures from the day-old rat ventricle and evaluated the effect of serum concentration and catecholamines on the growth process. Two single-cell preparations were used: serum-supplemented, bromodeoxyuridine-treated cultures and serum-free cultures with transferrin and insulin. Both preparations were characterized by myocardial cell predominance (about 75--80% of total cells) and constant cell numbers. Myocardial cell size was documented by photomicroscopy and quantified by volume (microscopic diameter of suspended cells), surface area (planimetry of attached cells), and total cell protein concentration (Lowry method and cell counts). Growth was also evaluated in pure nonmyocardial cell cultures. In cultures with 5% (vol/vol) serum, myocardial cell size increased 2- to 3-fold over 11 days in culture. Final volume, surface area, and protein concentration were about 3000 micrometer3/cell, 5000 micrometer2/cell, and 1500 pg/cell, respectively. Serum had a dose-related effect on myocardial cell hypertrophy; myocardial cell size increased about 4-fold when serum concentration was increased from 0% to 5% or 10%. Cells maintained in serum-free medium with transferrin and insulin (each 10 microgram/ml) did not hypertrophy, but did remain responsive to the growth-promoting activity of serum. Chronic exposure to isoproterenol or norepinephrine (1 microM) significantly stimulated myocardial cell hypertrophy. This stimulation was dose-related, was not blocked by equimolar propranolol, was not associated with a sustained chronotropic effect, and was more pronounced in the serum-free preparation. In pure cultures of nonproliferating (bromodeoxyuridine-treated) nonmyocardial cells, cell size also increased with time in culture, but variation in serum concentration and addition of norepinephrine had no significant effect on cell size. Myocardial cell hypertrophy occurs in culture and is regulated by variations in the culture medium, including serum, with its contained hormones and growth factors, and catecholamines. The culture preparation can be used to explore the regulation of myocardial cell hypertrophy by nonhemodynamic factors.
Circulating tumor cells in immunohistochemical subtypes of metastatic breast cancer: lack of prediction in HER2-positive disease treated with targeted therapy
Authors: A. Giordano, M. Giuliano, M. De Laurentiis, G. Arpino, S. Jackson, B.C. Handy, N.T. Ueno, E. Andreopoulou, R.H. Alvarez, V. Valero, S. De Placido, G.N. Hortobagyi, J.M. Reuben, M. Cristofanilli
Journal: Annals of Oncology (2011)
Relationship of mMRC and CAT scores in COPD patients
Authors: Georgios Kaltsakas, Nikoletta Rovina, Michael Symiakakis, Theodora Vasilogiannakopoyloy, Apostolos Travlos, Konstantinos Vlachos, Ioannis Vogiatzis, Nickolaos G. Koulouris
Journal: European Respiratory Journal (2013)

There are several validated questionnaires to assess symptoms in patients with COPD. For the assessment of symptoms in COPD, the GOLD document recommends either the use of a modified British Medical Research Council (mMRC) questionnaire or the chronic obstructive pulmonary disease assessment test score (CAT). Furthermore, GOLD proposes that a cut-off value of 2≤ in mMRC can substitute a cut-off value of 10≤ in CAT. However, no report can be found in the literature showing that those cut-off values are interchangeable. Therefore, we set out to investigate the relationship of those cut-off values.

We studied 89 (70 men) consecutive, Caucasian, COPD patients. They had (mean±SD): age=69±8 y, pack-years=100±74 y, FEV1, %pred=47±20, FVC, %pred=73±24, and FEV1/FVC, %=51±12. Chronic dyspnoea was rated according to the mMRC 5-point dyspnoea scale. Health status was measured with the CAT.

All patients reported some degree of dyspnoea (mMRC was 2.7±1.4). CAT score was 21±10. mMRC was significantly correlated with CAT score (r=0.788, p<0.0001). Backward stepwise regression between mMRC score and the individual CAT’s questions showed that some questions (1, 2, 7, and 8) did not significantly add to the capacity of the equation to predict the mMRC score (r=0.790, p<0.05). mMRC was ≥2 in 65/89 (73%) patients and CAT was ≥10 in 77/89 (87%) patients. Statistical analysis showed that those cut-off values were significantly correlated (p<0.001).

In COPD, mMRC dyspnoea score is closely related to CAT score, and hence these assessment tools may be used interchangeably.
Muscarinic effects of vagosympathetic trunk stimulation on the repetitive extrasystole (RE) threshold.
Authors: S H Rabinowitz, R L Verrier, B Lown
Journal: Circulation (1976)

The precise mechanism of the vagus in opposing adrenergic influences on cardiac vulnerability has not been defined. In the present investigation, cholinergic stimulation was produced by administering the selective muscarinic agent methacholine (MCh) and ventricular vulnerability was assessed by measuring the repetitive extrasystole (RE) threshold. MCh produced a sustained 98 +/- 12% (P less than 0.0001) increase in the RE threshold; the increase was abolished by concurrent infusion of atropine (0.2 mg/kg). When MCh was administered during beta-adrenergic blockade with propranolol, however, no further increase in RE threshold occurred beyond that resulting from propranolol alone. Infusion of norepinephrine (NE), in a dose insufficient to provoke systemic hypertension, significantly lowered the vulnerable period threshold. This decrease was completely abolished by concurrent vagosympathetic stimulation (VS). It is concluded that VS affects ventricular vulnerability through its muscarinic action and that the protection against VF is in part due to modulation of neural and humoral beta-adrenergic inputs.
FORMATION OF NON-INFECTIOUS INFLUENZA VIRUS IN MOUSE LUNGS: ITS DEPENDENCE UPON EXTENSIVE PULMONARY CONSOLIDATION INITIATED BY THE VIRAL INOCULUM
Authors: Harold S. Ginsberg
Journal: The Journal of Experimental Medicine (1954)

Formation of non-infectious virus-particles which hemagglutinate red blood cells and react with antibody to fix complement but do not infect the chick embryo or mouse-occurred when large quantities of certain strains of influenza viruses were inoculated intranasally into mice. Dependent upon the agent employed, 10(6.5) to 10(8.5) E.I.D. was essential to elicit this phenomenon. To accomplish this unusual multiplication it was essential to use a strain of virus which effected extensive pulmonary consolidation; strains of virus which did not produce marked lung lesions, even when as much as 10(8.5) E.I.D. was inoculated, did not form non-infectious virus. The development of this viral form was directly dependent upon the extent of cell damage obtained: consolidation of more than 50 per cent of the lung volume was required. The majority of non-infectious particles developed during the initial cycle of viral multiplication, and concurrently with the formation of non-infectious virus there was a corresponding decrease in the number of infectious viral particles. Non-infectious virus could not be propagated on serial passage in mouse lungs: on second lung passage only fully infectious virus was detectable. The formation of the non-infectious viral form was not the result of interference with synthesis of infectious virus by inactivated virus in the inoculum; for inoculation of heated infected allantoic fluid which contained more than 99 per cent of non-infectious virus did not result in the development of new non-infectious virus. Although inoculation of a large quantity of virus resulted in infection which yielded a relatively low titer of infectious and high titer of non-infectious virus, inoculation of a small quantity of the agent resulted in a high yield of infectious virus and no non-infectious that was detectable. In both instances the total quantity of antigenic viral material synthesized in the mouse lungs was the same. These data do not support the hypothesis that the non-infectious virus formed consisted of immature or incomplete viral particles, but suggest instead that non-infectious virus is inactivated virus or some aberrant form of the agent.
The Inflammasome Component Nlrp3 Impairs Antitumor Vaccine by Enhancing the Accumulation of Tumor-Associated Myeloid-Derived Suppressor Cells
Authors: Hendrik W. van Deventer, Joseph E. Burgents, Qing Ping Wu, Rita-Marie T. Woodford, W. June Brickey, Irving C. Allen, Erin McElvania-Tekippe, Jonathan S. Serody, Jenny P.-Y. Ting
Journal: Cancer Research (2010)

Abstract The inflammasome is a proteolysis complex that generates the active forms of the proinflammatory cytokines interleukin (IL)-1β and IL-18. Inflammasome activation is mediated by NLR proteins that respond to microbial and nonmicrobial stimuli. Among NLRs, NLRP3 senses the widest array of stimuli and enhances adaptive immunity. However, its role in antitumor immunity is unknown. Therefore, we evaluated the function of the NLRP3 inflammasome in the immune response using dendritic cell vaccination against the poorly immunogenic melanoma cell line B16-F10. Vaccination of Nlrp3−/− mice led to a relative 4-fold improvement in survival relative to control animals. Immunity depended on CD8+ T cells and exhibited immune specificity and memory. Increased vaccine efficacy in Nlrp3−/− hosts did not reflect differences in dendritic cells but rather differences in myeloid-derived suppressor cells (MDSC). Although Nlrp3 was expressed in MDSCs, the absence of Nlrp3 did not alter either their functional capacity to inhibit T cells or their presence in peripheral lymphoid tissues. Instead, the absence of Nlrp3 caused a 5-fold reduction in the number of tumor-associated MDSCs found in host mice. Adoptive transfer experiments also showed that Nlrp3−/− MDSCs were less efficient in reaching the tumor site. Depleting MDSCs with an anti–Gr-1 antibody increased the survival of tumor-bearing wild-type mice but not Nlrp3−/− mice. We concluded that Nlrp3 was critical for accumulation of MDSCs in tumors and for inhibition of antitumor T-cell immunity after dendritic cell vaccination. Our findings establish an unexpected role for Nlrp3 in impeding antitumor immune responses, suggesting novel approaches to improve the response to antitumor vaccines by limiting Nlrp3 signaling. Cancer Res; 70(24); 10161–9. ©2010 AACR.
FAMILIAL IDIOCY DUE TO NEURONAL LIPIDOSIS (SO-CALLED LATE AMAUROTIC IDIOCY)
Authors: GEORGE A. JERVIS
Journal: American Journal of Psychiatry (1950)

The case of a patient is described who showed slowly progressive mental deterioration with generalized muscular spasticity. No ocular manifestations were observed at any time. Death occurred at the age of 35 years. The patient was the seventh in a sibship of 12, 4 members of which were similarly affected. At pathologic examination, the characteristic picture of a ubiquitous neuronal lipidosis was found. The case is considered to be an instance of so-called late amaurotic idiocy. The main features of the disease are briefly discussed.
Ballantyne's Deafness
Authors: R P Mills
Journal: Journal of the Royal Society of Medicine (2002)

The past twenty years have seen considerable changes in the management of hearing impairment. Cochlear implantation has transformed the outlook for the profoundly deaf, and the way in which the outcomes have been monitored in the UK is a model for evidence-based practice. Hearing aid technology is changing, although there is so far no clear information on which patients will benefit from digital processing of sound. Important developments in screening of infants for hearing loss are currently being implemented. A new edition of Deafness, previously edited by John Ballantyne, is therefore welcome. The book is aimed at a wide readership including various professionals who encounter hearing-impaired people, individuals with hearing impairment and those who have a hearing-impaired relative. Topics include the structure and function of the ear, causes of hearing impairment and its assessment, its impact on mental wellbeing and the role of hearing aids of various sorts. The chapters are concise, well laid out and illustrated with clear line diagrams.

This type of book is much more difficult to write than one aimed at the authors' peers, since even basic concepts must be adequately explained and jargon studiously avoided. Most of the authors have succeeded but an exception is the chapter on acquired sensorineural hearing loss, which does not seem to have been written with a lay readership in mind. The opposite pitfall, of simplifying the content so much that it is of no value to professionals in related disciplines, does seem to have been avoided. In the chapter on the management of deafness in childhood the abbreviation SPL (sound pressure level) is used without explanation. Certain areas could have been covered better. The section on middle ear implants is somewhat out of date and not very informative. An account of the potential advantages of implantable hearing aids and the limitations of those currently available would have been more useful than the description of individual devices. These devices are not as yet part of the mainstream management of hearing loss, but patients and healthcare professionals will read about them in the press; a more authoritative account of their present status would have been helpful.

Overall my feeling is that this book will be of considerable use to a range of healthcare professionals and to deaf individuals and their relatives. It is therefore a worthy successor to previous editions.
Validation of the Toronto Clinical Scoring System for Diabetic Polyneuropathy
Authors: Vera Bril, Bruce A. Perkins
Journal: Diabetes Care (2002)

OBJECTIVE—The aim of the current study was to determine the validity of the Toronto Clinical Scoring System (CSS) in reflecting the presence and severity of diabetic peripheral sensorimotor polyneuropathy (DSP) as determined by myelinated fiber density (FD) on sural nerve biopsy. RESEARCH DESIGN AND METHODS—Eighty-nine patients with both type 1 and type 2 diabetes, ascertained from a large therapeutic randomized controlled trial, were included in this cross-sectional, observational cohort study. Morphological severity of DSP was expressed as the FD in the sural nerve biopsy. The Toronto CSS was applied to all patients to determine a clinical neuropathy score. General linear regression models were used to assess the relationship between the morphological severity of DSP and the Toronto CSS. RESULTS—The Toronto CSS showed a significant negative correlation with sural nerve FD (R2 = 0.256, P &amp;lt; 0.0001). The Toronto CSS was lower in those with better glycemic control (HbA1c ≤8%). Sural nerve FD and the Toronto CSS showed strong correlations with electrophysiology, by both summed amplitude and summed conduction velocity values. CONCLUSIONS—The Toronto CSS is a valid instrument to reflect the presence and severity of DSP as measured by sural nerve morphology and electrophysiology. The results of the current study underscore the interrelationships between clinical deficits, electrophysiological findings, and morphological changes in DSP. This evidence suggests that the Toronto CSS may prove useful in documenting and monitoring DSP in the clinic and in clinical research trials.
Vinorelbine alternating oral and intravenous plus carboplatinin advanced non-small-cell lung cancer: results of a multicentre phase II study
Authors: M.E.R. O’Brien, A. Szczesna, H. Karnicka, P. Zatloukal, T. Eisen, W. Hartmann, P. Kasan, B. Longerey, F. Lefresne
Journal: Annals of Oncology (2004)