tbuckley/cabot-search huggingface dataset:
The ubiquitin-proteasome system and nonsense-mediated mRNA decay in hypertrophic cardiomyopathy
Authors: L. Carrier, S. Schlossarek, M. S. Willis, T. Eschenhagen
Journal: Cardiovascular Research (2009)

Cardiomyopathies represent an important cause of cardiovascular morbidity and mortality due to heart failure, arrhythmias, and sudden death. Most forms of hypertrophic cardiomyopathy (HCM) are familial with an autosomal-dominant mode of inheritance. Over the last 20 years, the genetic basis of the disease has been largely unravelled. HCM is considered as a sarcomeropathy involving mutations in sarcomeric proteins, most often β-myosin heavy chain and cardiac myosin-binding protein C. 'Missense' mutations, more common in the former, are associated with dysfunctional proteins stably integrated into the sarcomere. 'Nonsense' and frameshift mutations, more common in the latter, are associated with low mRNA and protein levels derived from the diseased allele, leading to haploinsufficiency of the remaining healthy allele. The two quality control systems responsible for the removal of the affected mRNAs and proteins are the nonsense-mediated mRNA decay (NMD) and the ubiquitin-proteasome system (UPS), respectively. This review discusses clinical and genetic aspects of HCM and the role of NMD and UPS in the regulation of mutant proteins, evidence for impairment of UPS as a pathogenic factor, as well as potential therapies for HCM.
The rat liver microcirculation in alcohol-induced hepatomegaly
Authors: Ricardo Mastaï, P.-Michel Huet, Antoine Brault, Jocelyne Belgiorno
Journal: Hepatology (1989)

It has been suggested that hepatocyte enlargement can lead to compression of the extracellular space (sinusoidal and interstitial) and induce portal hypertension. However, this hypothesis has never been tested by measuring the vascular and extravascular spaces in the intact liver. The aim of the present study was to investigate the effects of chronic alcohol intake on the hepatic microcirculation using Goresky's multiple–indicator dilution technique in the isolated perfused rat liver. Female rat littermates were pair–fed either ethanol (n = 7) or an isocaloric carbohydrate diet (n = 7) for 21 days. As expected, chronic alcohol intake produced a significant increase in liver/body weight ratio (+32%, p &lt; 0.01) and hepatocyte size (+45%, p &lt; 0.001), which was accompanied by a marked increase in the cellular water space (control: 3.3 ± 0.6 ml; ethanol–fed: 4.9 ± 0.9 ml; p &lt; 0.001). When expressing data per total liver, the sinusoidal space was similar in the two groups (control: 1.87 ± 0.2; ethanol–fed: 1.95 ± 0.2 ml; not significant), whereas the interstitial space was increased in alcohol rats compared to controls (albumin space +58%, p &lt; 0.01; sucrose space +51%, p &lt; 0.01). In alcoholic rats, the sinusoidal space was probably stretched, with an overall reduced transversal diameter, as suggested by the reduced values found when data were expressed per gm of liver weight. However, despite this finding and the enlargement of the liver and hepatocytes observed in alcoholic rats, similar values were obtained between the two groups for the portal perfusion pressure and thus the intrahepatic vascular resistance. The present data show that the enlargement of the liver and hepatocytes due to chronic alcoholic intake: (i) does not develop at the expense of the total vascular space and unexpectedly increases the interstitial space, and (ii) under our experimental conditions, does not modify the overall resistance of the liver.
In public health, evidence should dictate policy (mostly)
Authors: G. Watts
Journal: BMJ (2010)

When the question to be discussed is “Public health: should evidence always dictate policy?”, when five panellists assembled to answer it all have some standing in science or medicine, and when the venue is the Royal Society of Medicine, you don’t really expect anyone to say, “No, it shouldn’t.” And no one did. But the spread of views was wider than the audience might have anticipated.

Held on 18 October as a satellite event in the annual conference series put on by the Institute of Ideas, the meeting began with the views of Nigel Hawkes, BMJ columnist and director of Straight Statistics (www.straightstatistics.org). Evidence, he said, is necessary but not …
A respiratory survey in a black Johannesburg workforce.
Authors: K E Mokoetle, M de Beer, M R Becklake
Journal: Thorax (1994)

The burden and determinants of airway disease in the population of southern Africa, which is currently undergoing rapid, often uncontrolled, urbanisation and industrialisation, are unknown. Previous surveys have focused on specific occupational groups and few have included women. This paper describes the respiratory status in a 30% probability sample of 206 men and 203 women drawn from an urban black Johannesburg workforce of almost 1500, all working for an educational institution.Subjects answered a respiratory questionnaire and performed spirometric tests. Symptom rates and age and height standardised forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC%, and forced expiratory flow (FEF25-75) were analysed by gender in relation to smoking, past work exposures, past and recent respiratory conditions, and socioeconomic indicators.Symptom prevalence was high, bronchitic symptoms in men being related to smoking and previous occupational exposure, and in women to smoking despite the low intensity of their habit. Phlegm and wheezing were related to childhood respiratory illness in both men and women. FVC and FEV1, based on all subjects including smokers, were higher than previously reported for black residents of southern Africa. FVC was also positively related to education and job category. Higher values for ever smokers than for never smokers suggested health selection into the habit, while significant negative smoking effects were seen only on FEV1/FVC% and only in women.Despite the high prevalence of symptoms--some smoking related--in this urban workforce, lung function levels were higher than previously reported in African blacks, and may reflect improving socioeconomic conditions.
S46 Phagocytosis By Blood Neutrophils Is Not Attenuated In Patients With Chronic Obstructive Pulmonary Disease
Authors: G. Walton, T. Purvis, C. Chadwick, R. Stockley, E. Sapey
Journal: Thorax (2014)

<h3>Rationale</h3> All COPD phenotypes have airway neutrophilia but,despite this, bacteria associated infections are common, relate to decline and a significant proportion of patients have persistent airway colonisation. This is suggestive of innate immune dysfunction. <i>In vitro</i> studies have shown reduced neutrophil migratory accuracy in COPD (Sapey, Stockley <i>et al</i>. 2011) however, the ability of the neutrophil to contain bacterial infection upon arrival at a site of infection is poorly understood. Literature regarding the phagocytic ability of neutrophils from patients with COPD is conflicting and inconclusive. It is unclear whether responses change depending on the bacterial species present. We hypothesised that neutrophil phagocytosis during COPD is impaired, predisposing patients to increased inflammation and reduced bacterial clearance. <h3>Methods</h3> Blood neutrophils were isolated from stable-state COPD patients and healthy age-matched controls (HC). Phagocytosis of both opsonised (with 10% pooled COPD serum) and unopsonised pHrodo™-conjugated <i>Staphylococcus aureus </i>bioparticles (SA, n = 20), or E<i>scherichia coli</i> bioparticles (EC, n = 10) and fluorescently labelled disease-relevant bacteria, <i>Haemophilus influenzae</i> (HI, n = 10) and <i>Streptococcus pneumoniae</i> (SP, n = 10) was assessed, at regular intervals over 60 min, using flow-cytometry. Results were confirmed using time-lapse video microscopy. <h3>Results</h3> Peak phagocytosis was achieved at 60 min for unopsonised bacteria and 30 min for opsonised bacteria. There were no differences in time to peak phagocytosis between bacterial species. Blood neutrophils from patients with COPD and HC displayed similar phagocytic ability, in both percentage of neutrophils with phagocytic activity and the amount of SA, EC, HI or SP ingested (as indicated by MFI) (COPD vs. HC, p &gt; 0.05 for all). This was ubiquitous to both opsonin independent and opsonin-dependant phagocytosis, and was consistent across all time points measured. A typical comparison is shown in figure one, with unopsonised SA data. <h3>Conclusions</h3> Phagocytic ability of blood neutrophils from patients with COPD to ingest <i>Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae </i>and<i> Haemophilus influenzae </i>is not altered compared to age-matched healthy controls. This should be replicated in lung neutrophils to assess whether transmigration to the tissues affects function.
Physician Referral for Fertility Preservation in Oncology Patients: A National Study of Practice Behaviors
Authors: Gwendolyn P. Quinn, Susan T. Vadaparampil, Ji-Hyun Lee, Paul B. Jacobsen, Gerold Bepler, Johnathan Lancaster, David L. Keefe, Terrance L. Albrecht
Journal: Journal of Clinical Oncology (2009)

Cancer survival rates are improving, and the focus is moving toward quality survival. Fertility is a key aspect of quality of life for cancer patients of childbearing age. Although cancer treatment may impair fertility, some patients may benefit from referral to a specialist before treatment. However, the majority of studies examining patient recall of discussion and referral for fertility preservation (FP) show that less than half receive this information. This study examined the referral practices of oncologists in the United States.This study examined oncologists' referral practice patterns for FP among US physicians using the American Medical Association Physician Masterfile database. A 53-item survey was administered via mail and Internet to a stratified random sample of US physicians.Forty-seven percent of respondents routinely refer cancer patients of childbearing age to a reproductive endocrinologist. Referrals were more likely among female physicians (P = .004), those with favorable attitudes (P = .043), and those whose patients routinely ask about FP (odds ratio = 2.09; 95% CI, 1.31 to 3.33).Less than half of US physicians are following the guidelines from the American Society of Clinical Oncology, which suggest that all patients of childbearing age should be informed about FP.
Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis
Authors: Adam M. Petrich, Mitul Gandhi, Borko Jovanovic, Jorge J. Castillo, Saurabh Rajguru, David T. Yang, Khushboo A. Shah, Jeremy D. Whyman, Frederick Lansigan, Francisco J. Hernandez-Ilizaliturri, Lisa X. Lee, Stefan K. Barta, Shruthi Melinamani, Reem Karmali, Camille Adeimy, Scott Smith, Neil Dalal, Chadi Nabhan, David Peace, Julie Vose, Andrew M. Evens, Namrata Shah, Timothy S. Fenske, Andrew D. Zelenetz, Daniel J. Landsburg, Christina Howlett, Anthony Mato, Michael Jaglal, Julio C. Chavez, Judy P. Tsai, Nishitha Reddy, Shaoying Li, Caitlin Handler, Christopher R. Flowers, Jonathon B. Cohen, Kristie A. Blum, Kevin Song, Haowei (Linda) Sun, Oliver Press, Ryan Cassaday, Jesse Jaso, L. Jeffrey Medeiros, Aliyah R. Sohani, Jeremy S. Abramson
Journal: Blood (2014)
Outcome prediction in terms of functional disability and mortality at 1�year among ICU-admitted severe stroke patients: a prospective epidemiological study in the south of the European Union (Evascan Project, Andalusia, Spain)
Authors: Pedro Navarrete-Navarro, Ricardo Rivera-Fern�ndez, Maria Teresa L�pez-Mutuberr�a, Inmaculada Galindo, Francisco Murillo, Jos� Mar�a Dominguez, Angeles Mu�oz, Jos� Manuel Jimenez-Moragas, Bel�n Nacle, Guillermo V�zquez-Mata
Journal: Intensive Care Medicine (2003)
B-glucuronidase activity of gastric juice in gastric carcinoma.
Authors: R I Russell, C Watts
Journal: Gut (1968)

Carcinoma of the stomach is often not diagnosed until the disease has spread extensively.Attempts have thus been made to find additional methods which may be of value in earlier diagnosis.A test of gastric secretory function would be of great value if it were able to show distinctive changes in gastric carcinoma but so far this has not been achieved (Hitchcock and Aust, 1955; Fischermann and Koster, 1962; Gilbertsen and Knatterud, 1967).Electrophoresis of gastric juice proteins has shown minor quantitative changes which are of little diagnostic importance (Piper, Stiel, and Builder, 1963b).More recently, several workers have turned their attention to the estimation of non-proteolytic enzymes in gastric juice and their relation to disease processes.Schenker (1959) measured lactic dehydrogenase in gastric juice and found raised levels in some cases of gastric carcinoma.These findings were confirmed by Levitan, Golub, and Zetzel (1960) and Smymiotis, Schenker, O'Donnell, and Schiff (1962), although in the latter case, tests were performed only on patients exhibiting achlorhydria.Piper, Macoun, Builder, and Fenton (1963a) measured a series of non-proteolytic enzymes in the gastric juice, and found that for two of them, lactic dehydrogenase and B-glucuronidase, the levels were raised in some cases of carcinoma of stomach.The former enzyme was present in normal amounts in anaplastic tumours although elevated in most adenocarcin- omas; thus attention was focused on the latter enzyme, B-glucuronidase, as being of possible diagnostic value in gastric carcinoma.B-Glucuronidase is a lysozomal enzyme involved in the hydrolysis of B-D-glucosiduronic acid (de Duve, Pressman, Gianetto, Wattiaux, and Appelmans, 1955; de Duve, 1961).It is widely distributed throughout animal tissues.High levels of B-glucuronidase were found in homogenates of human gastric tumour tissue by Fishman and Anlyan (1947) and in several body fluids associated with
Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.
Authors: E R Mathiesen, E Hommel, J Giese, H H Parving
Journal: BMJ (1991)

OBJECTIVE--To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy (albuminuria greater than 300 mg/24h). DESIGN--Open randomised controlled study of four years9 duration. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--44 normotensive (mean blood pressure 127/78 (SD 12/10) mm Hg) insulin dependent diabetic patients with persistent microalbuminuria (30-300 mg/24h). INTERVENTIONS--The treatment group (n = 21) was initially given captopril (25 mg/24 h). The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months. The remaining 23 patients were left untreated. MAIN OUTCOME MEASURES--Albuminuria, kidney function, development of diabetic nephropathy (albuminuria greater than 300 mg/24 h), and arterial blood pressure. RESULTS--Clinical and laboratory variables were comparable at baseline. Urinary excretion of albumin was gradually reduced from 82 (66-106) to 57 (39-85) mg/24 h (geometric mean (95% confidence interval)) in the captopril treated group, whereas an increase from 105(77-153) to 166 (83-323) mg/24 h occurred in the control group (p less than 0.05). Seven of the untreated patients progressed to diabetic nephropathy, whereas none of the captopril treated patients developed clinical overt diabetic nephropathy (p less than 0.05). Systemic blood pressure, glomerular filtration rate, haemoglobin A1c concentration, and urinary excretion of sodium and urea remained practically unchanged in the two groups. CONCLUSIONS--The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria.
"REPORT OF A CASE OF PRIMARY TUBERCULOSIS OF FAUCIAL TONSILS"
Authors: Dunbar Roy
Journal: JAMA (1918)

To the Editor:  —InThe Journal, September 21, there appeared a Report of a Case of Primary Tuberculosis of the Faucial Tonsils by Major T. E. Oertel and Capt. George A. Griot of Camp Logan. Texas. I am sure that on further study of this case the authors would not report it as one of primary tuberculosis of the faucial tonsils. That it was one of tuberculosis could not be questioned; but the history of the case, as given, would certainly lead us to class it as one of secondary tuberculosis following an infection in the lungs. The fact that the larynx and trachea showed such marked tuberculous changes would certainly preclude the possibility of knowing which: was the first to be affected. My observations do not lead me to believe in even primary tuberculosis of the larynx, and I am sure it would be difficult to find a case
Diabetes Mellitus and Cigarette Smoking: Findings from the 1989 National Health Interview Survey
Authors: Earl S Ford, Ann M Malarcher, William H Herman, Ron E Aubert
Journal: Diabetes Care (1994)

OBJECTIVE To compare the prevalence of current smoking in the U. S. diabetic population with that of the nondiabetic population. RESEARCH DESIGN AND METHODS Using data from the 1989 National Health Interview Survey—a nationally representative sample—we calculated the prevalence of current smoking for 2,405 people with self-reported diabetes and 20,131 people without this condition. RESULTS Overall, the age-adjusted prevalence of smoking was 27.3% among people with diabetes and 25.9% among people without diabetes. The prevalence of smoking did not differ significantly between participants with and without diabetes when they were stratified by age, sex, race, or education. Black and Hispanic men with diabetes had a higher prevalence of smoking than did white men with diabetes and black and Hispanic men without diabetes, but none of these differences were statistically significant. Among people with diabetes, age, race, sex, and educational status were independent predictors of current smoking in a multiple-logistic regression model. Duration of diabetes was not related to smoking. CONCLUSIONS These data again emphasize the need to prevent and reduce smoking in the diabetic population. Smoking cessation programs should particularly target people with diabetes who are ≤44 years of age. Black and Hispanic men are also prime targets for intervention efforts.
Legal Problems Related to the Care of the Mentally Ill
Authors: C. H. Hardin Branch
Journal: New England Journal of Medicine (1963)

WHEN Pinel, about the end of the eighteenth century, struck the chains from the patients at the Salpêtrière, he struck at the same time a blow toward the handling of mentally ill patients exactly like any other patients; in other words, he identified them as being "sick" rather than "bad" people, objects of scorn, ridicule and fear. This process was continued by various humanitarian psychiatrists and lay groups. Very recently, for example, the National Association for Mental Health has widely publicized a campaign to beat the last remaining manacles, bars and so forth into metal that could be used to . . .
Abstract 1230: Impact of apheresis (Aph) on number and function of lymphocytes in cancer patients (pts).
Authors: James L. Gulley, Christopher R. Heery, Seth Steinberg, Jenn Marte, Ravi A. Madan, Jeffrey Schlom
Journal: Cancer Research (2013)

Abstract It has been suggested that Aph, used for Sipuleucel-T, may negatively affect the OS of cancer pts by removing circulating lymphocytes and diminishing host immunity. We explored data from prior clinical trials in which pts had Aph or simple phlebotomy for evidence to support or contradict this. We examined data from cancer pts on clinical trials who had Aph (n=64) or only peripheral blood draws (n=90) as controls for immune analysis. As the 1° functional analysis, we evaluated the impact of Aph on the flu specific T-cells using ELISPOT. We also evaluated the impact on absolute lymphocyte count (ALC), T cells (CD3, CD4, CD8, and CD4:CD8 ratio). ELISPOT was expressed as number of cells/spot (i.e. 1/10,000 would be expressed as 10,000). For all parameters, baseline (pre) values were compared to post-treatment (post) values using a Wilcoxon signed rank test. A large two-tailed p-value would indicate no significant change in values. Findings from smaller groups who underwent Aph multiple times are described. In the Aph group, the median age was 63 (range 38-82); 92% male. Comparing the pre and post values within the groups, with each pt as its own control, there was no significant difference when comparing ELISPOT, ALC, and T cells (Table). 13 pts had a 3rd Aph with ELISPOT; 7 had improved responses to flu with an even distribution around no change. 29 pts underwent &amp;gt;2 Aph (range 3-19, median 4), 20 with matched ALC and 20 with T cell values. There was a trend toward a slight decrease (&amp;lt;10%) in ALC and T cell subsets. These findings supported the statistical analysis, which identified no consistently positive or negative change in pts who received Aph. This analysis indicates there is no difference in the number and function of immune cells post Aph in cancer pts. This data provides evidence that Aph inflicts negligible effects on a pts immune system, rejecting the hypothesis that pts immune competence is impacted by the procedure in a meaningful way. Post minus pre valuesELISPOT (n = 64)ALC (n = 52)CD3 (n = 36)CD4 (n = 36)CD8 (n = 36)CD4:CD8 ratio (n = 15)Aph groupDifference Pre vs PostMean500.906−0.02133.72102.7219.420.51Median0.000.0097.5063.5020.000.23P value1.000.780.0360.0240.560.0045InterpretationNo changeNo changeTrend IncreaseTrend IncreaseNo changeSignificant IncreaseNon-Aph group N = 90Difference Pre vs PostMean500.600Median0.00P value1.00 Citation Format: James L. Gulley, Christopher R. Heery, Seth Steinberg, Jenn Marte, Ravi A. Madan, Jeffrey Schlom. Impact of apheresis (Aph) on number and function of lymphocytes in cancer patients (pts). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1230. doi:10.1158/1538-7445.AM2013-1230
MHC-restricted recognition of immunogenic T cell epitopes of pertussis toxin reveals determinants in man distinct from the ADP-ribosylase active site.
Authors: J R Oksenberg, A K Judd, C Ko, M Lim, R Fernandez, G K Schoolnik, L Steinman
Journal: The Journal of Experimental Medicine (1988)

The S1 subunit of Pertussis toxin (PT) is responsible for the reactogenicity and in part the immunogenicity of Bordetella pertussis vaccine. The critical residues associated with the immunomodulatory effects of PT were located around Glu140 in the S1 subunit. In man, T cell responses to PT are directed at S1 peptides distinct from Glu140. Two such epitopes, p64-75 and p151-161, are immunogenic in a panel of individuals covering a wide range of HLA genotypes. The response to PT peptides is HLA class II restricted. The response to p64-75 is blocked by an anti-HLA-DQ mAb, while that to p151-161 is blocked by an anti-HLA-DR mAb. These findings may allow for the development of a B. pertussis vaccine free from reactogenicity.