tbuckley/cabot-search huggingface dataset:
Effect of Dose on Immune Response in Patients Vaccinated With an HER-2/neu Intracellular Domain Protein—Based Vaccine
Authors: Mary L. Disis, Kathy Schiffman, Katherine Guthrie, Lupe G. Salazar, Keith L. Knutson, Vivian Goodell, Corazon dela Rosa, Martin A. Cheever
Journal: Journal of Clinical Oncology (2004)

To evaluate the safety of an HER-2/neu intracellular domain (ICD) protein vaccine and to estimate whether vaccine dose impacts immunogenicity.Twenty-nine patients with HER-2/neu-overexpressing breast or ovarian cancer and with no evidence of disease after standard therapy received a low- (25 microg), intermediate- (150 microg), or high-dose (900 microg) HER-2/neu ICD protein vaccine. The vaccine was administered intradermally, monthly for 6 months, with granulocyte-macrophage colony-stimulating factor as an adjuvant. Toxicity and both cellular and humoral HER-2/neu-specific immunity was evaluated.The vaccine was well tolerated. The majority of patients (89%) developed HER-2/neu ICD-specific T-cell immunity. The dose of vaccine did not predict the magnitude of the T-cell response. The majority of patients (82%) also developed HER-2/neu-specific immunoglobulin G antibody immunity. Vaccine dose did not predict magnitude or avidity of the HER-2/neu-specific humoral immune response. Time to development of detectable HER-2/neu-specific immunity, however, was significantly earlier for the high- versus low-dose vaccine group (P =.003). Over half the patients retained HER-2/neu-specific T-cell immunity 9 to 12 months after immunizations had ended.The HER-2/neu ICD protein vaccine was well tolerated and effective in eliciting HER-2/neu-specific T-cell and antibody immunity in the majority of breast and ovarian cancer patients who completed the vaccine regimen. Although the dose of vaccine did not impact the magnitude of T-cell or antibody immunity elicited, patients receiving the highest dose developed HER-2/neu-specific immunity more rapidly than those who received the lowest dose.
Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis
Authors: E. Gamble, D. C. Grootendorst, K. Hattotuwa, T. O'Shaughnessy, F. S. F. Ram, Y. Qiu, J. Zhu, A. M. Vignola, C. Kroegel, F. Morell, I. D. Pavord, K. F. Rabe, P. K. Jeffery, N. C. Barnes
Journal: European Respiratory Journal (2007)

Bronchial biopsy specimens from chronic obstructive pulmonary disease (COPD) patients demonstrate increased numbers of CD8+ T-lymphocytes, macrophages and, in some studies, neutrophils and eosinophils. Smoking cessation affects the rate of forced expiratory volume in one second (FEV 1 ) decline in COPD, but the effect on inflammation is uncertain. Bronchial biopsy inflammatory cell counts were compared in current and ex-smokers with COPD. A pooled analysis of subepithelial inflammatory cell count data from three bronchial biopsy studies that included COPD patients who were either current or ex-smokers was performed. Cell count data from 101 subjects, 65 current smokers and 36 ex-smokers, were analysed for the following cell types: CD4+ and CD8+ T-lymphocytes, CD68+ (monocytes/macrophages), neutrophil elastase+ (neutrophils), EG2+ (eosinophils), mast cell tryptase+ and cells mRNA-positive for tumour necrosis factor-α. Current smokers and ex-smokers were similar in terms of lung function, as measured by FEV 1 (% predicted), forced vital capacity (FVC) and FEV 1 /FVC. The results demonstrate that there were no significant differences between smokers and ex-smokers in the numbers of any of the inflammatory cell types or markers analysed. It is concluded that, in established chronic obstructive pulmonary disease, the bronchial mucosal inflammatory cell infiltrate is similar in ex-smokers and those that continue to smoke.
Toxicity modeling and prediction with pattern recognition.
Authors: S Wold, W J Dunn, S Hellberg
Journal: Environmental Health Perspectives (1985)

Empirical models can be constructed relating the change in toxicity to the change in chemical structure for series of similar compounds or mixtures. The first step is to translate the variation in structure to quantitative numbers. This gives a data table, a data matrix denoted by X, which then is analyzed. The same type of the models can be used to relate the variation of in vivo data to the variation of a battery of in vitro tests. A single data analytical model cannot be applied to a set of compounds of diverse chemical structure. For such data sets, separate models must be developed for each subgroup of compounds. The data analytical problem then partly is one of classification, pattern recognition (PARC). The assumption of structural and biological similarity within each subset of modeled compounds is then essential for empirical models to apply. PARC is often used to classify compounds as active (toxic) or inactive. The data structure is then often asymmetric which puts special demands on the data analysis, making the traditional PARC methods inapplicable. Depending on the desired information from the data analysis and on the type of available data, four levels of PARC can be distinguished: (I) the data X are used to develop rules for classifying future compounds into one of the classes represented in X; (II) same as I, but the possibility of future compounds belonging to "unknown" classes not represented in X is taken into account; (III) same as II, plus the quantitative prediction of one activity variable (here toxicity) in some classes; (IV) same as III, but several quantitative activity (toxicity) variables are predicted.
Silent gastro-oesophageal reflux and microaspiration in IPF: mounting evidence for anti-reflux therapy?
Authors: G. Raghu, K.C. Meyer
Journal: European Respiratory Journal (2012)

Idiopathic pulmonary fibrosis (IPF) is a distinct clinical entity that generally affects people who are over 60 yrs of age, and median survival ranges from 3 to 5 yrs after the diagnosis is ascertained. The natural course of IPF is well known: the majority of patients with IPF display steady decline in lung function, some patients remain stable for prolonged periods of time, a subgroup of patients rapidly decline, and a subset of patients manifest acute exacerbations of IPF preceding death [1]. While several key cellular and molecular events that are thought to follow “injury” have been identified in the pathogenesis of IPF [2], the ultimate cause of IPF and the triggering factor(s) that injure the lung remain elusive, and none of the currently available pharmacological agents have demonstrated improved outcomes and survival in patients with IPF.

The incidence and prevalence of IPF is highly linked to advanced age with an estimated incidence and prevalence of 71 and 271 per 100,000 per year for males and 67 and 266 per 100,000 per year for females aged 75 yrs or greater versus an overall incidence and prevalence of 16.3 and 42.7 per 100,000 per year using broad diagnostic criteria [3]. Interestingly, many observations suggest that the aged lung is more susceptible to injury and fibrosis induced by a variety of stimuli, and this susceptibility may be linked to age-associated changes in gene expression or genetic polymorphisms such as age-associated telomerase dysfunction [4–7].

Advanced age is also accompanied by a decline in oesophageal and gastric motility, diminished upper oesophageal sphincter pressure, and an increase in oesophageal acid exposure [8]. Hiatal hernias appear with advancing age and have been detected in up to 60% of individuals older than 60 yrs [ …
A phase III, randomized, double-blind, placebo-controlled study of peldesine (BCX-34) cream as topical therapy for cutaneous T-cell lymphoma
Authors: Madeleine Duvic, Elise A. Olsen, George A. Omura, John C. Maize, Eric C. Vonderheid, Craig A. Elmets, Jerome L. Shupack, Marie-France Demierre, Timothy M. Kuzel, Deborah Y. Sanders
Journal: Journal of the American Academy of Dermatology (2001)
Reduction of Low-Density Lipoprotein Cholesterol by Monoclonal Antibody Inhibition of PCSK9
Authors: Evan A. Stein, Frederick Raal
Journal: Annual Review of Medicine (2014)

Published phase I and II trials with two fully human monoclonal antibodies to PCSK9 have provided comprehensive evidence that inhibiting PCSK9 is a very effective method to reduce low-density lipoprotein cholesterol (LDL-C). In all populations studied so far, whether on statins or LDL-C-reducing diet alone, with or without a genetic defect in the LDL receptor, and in subjects intolerant to statins, the LDL-C reductions have been large and consistent. Even the most efficacious statin, rosuvastatin, at its highest dose has not achieved such reductions. The clinical trials have established that monoclonal antibody therapy targeted to PCSK9 may be administered subcutaneously every two or four weeks. Current data suggest these drugs will provide an effective therapeutic option for LDL-C reduction and that, if proven safe in phase III trials, they will be as important to LDL-C control, and likely to cardiovascular disease risk reduction, as statins have been over the past three decades.
Twenty-two year (1975 to 1997) trends in the incidence, in-hospital and long-term case fatality rates from initial q-wave and non-q-wave myocardial infarction: a multi-hospital, community-wide perspective
Authors: Mark I Furman, Harold L Dauerman, Robert J Goldberg, Jorge Yarzbeski, Darleen Lessard, Joel M Gore
Journal: Journal of the American College of Cardiology (2001)
Fulminant hepatic failure — outcome after listing for highly urgent liver transplantation — impact of AB0 blood type
Authors: B. Brandsaeter, K. Höckerstedt, B. Hansen, B.G. Ericzon, K. Bjøro, M. Olausson, H. Isoniemi, P. Kirkegaard, G. Söderdahl, A. Foss, S. Friman
Journal: Journal of Hepatology (2001)
Use of Hematopoietic Colony-Stimulating Factors: Comparison of the 1994 and 1997 American Society of Clinical Oncology Surveys Regarding ASCO Clinical Practice Guidelines
Authors: Charles L. Bennett, Jane A. Weeks, Mark R. Somerfield, Joe Feinglass, Thomas J. Smith
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The American Society of Clinical Oncology (ASCO) Health Services Research Committee sought to assess whether more appropriate patterns of colony-stimulating factor (CSF) use occurred after the publication of ASCO evidence-based practice guidelines in 1994 and 1996 for patients with solid tumors or lymphoma. METHODS: In 1994 and 1997, questionnaires describing clinical scenarios were mailed to ASCO members who practiced medical oncology. Physicians were asked the extent to which they preferred to use a CSF for primary prophylaxis, secondary prophylaxis, or treatment of neutropenic complications. Multiple regression analyses were used to determine predictors of overall propensity to use CSFs and, when using a CSF, propensity to support longer schedules of CSF use. RESULTS: Decreased use of CSFs was shown in the following situations: (1) treatment for febrile neutropenia without localizing signs (39% in 1994 v 29% in 1997) or with a right lower lobe infiltrate (54% v 46%); (2) primary prophylaxis with paclitaxel for ovarian cancer (20% v 11%) or cyclophosphamide, doxorubicin, and vincristine chemotherapy for small-cell lung cancer (8.4% v 4.6%); and (3) secondary prophylaxis after afebrile neutropenia following chemotherapy for germ cell tumors (44.5% v 36.0%). One third fewer physicians supported the extended use of CSFs until an absolute neutrophil count ≥ 10,000/mm 3 or a WBC count ≥ 10,000/mm 3 was reached, both counts serving as criteria for stopping CSF therapy. However, we observed high rates of CSF use despite ASCO guideline recommendations against use in the following clinical situations: (1) primary prophylaxis in patients at low risk of febrile neutropenia (6% v 16%); (2) secondary prophylaxis late in the course of curative and palliative therapy (80% v 53%); and (3) treatment of afebrile and uncomplicated febrile neutropenia (30% v 60%). In 1994 and 1997, fee-for-service physicians were more likely than other physicians to prefer use of CSF support while maintaining treatment dose and schedule instead of using dose-reduction strategies, and, when using a CSF, they were more likely to support longer CSF treatment schedules (P &lt; .05 for both scenarios). CONCLUSION: Decreased use and more appropriate use of CSFs in accordance with ASCO guideline recommendations occurred from 1994 to 1997, but there remain many opportunities to reduce CSF use with no clinical harm. Many oncologists continue to support the use of CSFs in scenarios and with scheduling criteria that the guidelines and evidence do not support. ASCO's evidence-based guidelines should be linked with formal continuous quality improvement initiatives to substantially improve the quality of supportive oncology care.
Intima-media thickness of the carotid artery and the distribution of lipoprotein subclasses in men aged 40 to 49 years between whites in the United States and the Japanese in Japan for the ERA JUMP study
Authors: Akira Sekikawa, Hirotsugu Ueshima, Kim Sutton-Tyrrell, Takashi Kadowaki, Aiman El-Saed, Tomonori Okamura, Tomoko Takamiya, Yoshiki Ueno, Rhobert W. Evans, Yasuyuki Nakamura, Daniel Edmundowicz, Atsunori Kashiwagi, Hiroshi Maegawa, Lewis H. Kuller
Journal: Metabolism (2008)
Can ultrasonography improve on radiographic assessment in osteoarthritis of the hands? A comparison between radiographic and ultrasonographic detected pathology
Authors: H I Keen, R J Wakefield, A J Grainger, E M A Hensor, P Emery, P G Conaghan
Journal: Annals of the Rheumatic Diseases (2007)

Ultrasonography (US) is used in rheumatology to assess small joints in inflammatory arthritis. Recently there has been some investigation into the utility of US in osteoarthritis (OA), however there has been little comparison of US to other imaging modalities in OA. This study aimed to compare the detection of osteophytosis and joint space narrowing (JSN) by US and conventional radiography (CR) in OA of the hand.with OA of the hand underwent US and CR examination of the small joints of both hands to identify osteophytosis and joint space narrowing.1106 joints of 37 patients were imaged with US and CR. US detected osteophytosis in 448 joints, compared to CR that detected osteophytosis in 228 joints (approximately 30% fewer joints). Where osteophytosis was detected by US but not CR, this was usually proximal to the joint line. Joint space narrowing was detected in 450 joints by US, but only 261 joints by CR. The distribution of US and CR detected osteoarthritis changes in this cohort was consistent with population studies of radiographic hand OA, although metacarpophalangeal (MCP) involvement was higher than might be expectedUS detected more osteophytosis and joint space narrowing than CR in OA of the hand. Involvement of MCP joints was more common than would be expected from population radiographic studies. The increased detection of OA structural pathology by US may make this a useful tool for hand OA research.
The influence of sex, body weight, and renal function on the xylose test
Authors: M. J. Kendall, S. Nutter
Journal: Gut (1970)

A low excretion of xylose may be due to malabsorption, renal disease, or old age. Malabsorption can be distinguished from other causes by performing a combined oral and intravenous test, the result being expressed as a fraction of these readings. Sex and body weight do not influence the xylose test.
Demonstration of independent roles of proximal tubular reabsorption and intratubular load in the phenomenon of glomerulotubular balance during aortic constriction in the rat
Authors: Wolf E. Buentig, Laurence E. Earley
Journal: Journal of Clinical Investigation (1971)

The mechanism of glomerulotubular balance was investigated by microperfusion of the rat proximal tubule at two different rates before and after contriction of the aorta sufficient to produce a 50% reduction in whole kidney filtration rate and plasma flow. At a perfusion rate of 28 nl/min the absolute rate of proximal tubular reabsorption averaged 4.80+/-0.28 nl/mm.min in the absence of aortic constriction. Reducing the perfusion rate by one-half resulted in only a 22% decrease in the absolute rate of reabsorption, and imbalance between load and reabsorption resulted as fractional reabsorption of the perfused volume increased from 0.56 to 0.83 at 3 mm length of perfused tubule. These observations support other studies indicating that changing the load presented to the individual proximal tubule does not change reabsorptive rate sufficiently to result in glomerulotubular balance. Aortic constriction decreased the absolute rate of proximal tubular reabsorption approximately 50%, resulting in imbalance between load and reabsorption at the higher perfusion rate (fractional reabsorption of the perfused volume fell to 0.23 at 3 mm). Thus, the decrease in proximal tubular reabsorption necessary for glomerulotubular balance will occur independent of a change in the load presented for reabsorption. Balance between load and reabsorption was produced artificially by combining aortic constriction and a reduction in perfusion rate proportional to the reduction in whole kidney filtration rate. Mathematical analysis of the data suggests that the absolute rate of reabsorption along the accessible length of the proximal tubule is constant and is not proportional to the volume of fluid reaching a given site. Thus, there appears to be no contribution to glomerulotubular balance of any intra- or extratubular mechanism directly coupling load and the rate of proximal tubular reabsorption. It is concluded that glomerulotubular balance during aortic constriction is a consequence of hemodynamic effects of the maneuver to decrease filtration rate and the rate of proximal tubular reabsorption independently but in an approximately proportional manner.
Predicting death due to progressive heart failure in patients with mild-to-moderate chronic heart failure
Authors: Mark T Kearney, Keith A.A Fox, Amanda J Lee, Robin J Prescott, Ajay M Shah, Philip D Batin, Wazir Baig, Stephen Lindsay, Timothy S Callahan, William E Shell, Dwain L Eckberg, Azfar G Zaman, Simon Williams, James M.M Neilson, James Nolan
Journal: Journal of the American College of Cardiology (2002)
Delivering Erythropoietin through Genetically Engineered Cells
Authors: DELPHINE BOHL, JEAN-MICHEL HEARD
Journal: Journal of the American Society of Nephrology (2000)

Erythropoietin (Epo) is a glycoprotein hormone produced by genetic engineering. Many pathologic conditions could benefit from its administration, such as chronic renal failure or hemoglobinopathies. Epo secretion from genetically modified tissued could be proposed to patients only if the protocol is low cost and low risk. For that purpose, retroviral vectors and adeno-associated vectors expressing the Epo cDNA were developed. Gene transfer was performed into skeletal muscles. To avoid polycythemia, a tetracycline-regulated system was used to control the levels of protein secretion in vivo. beta-thalassemias are among diseases that could benefit from an Epo gene transfer. beta-thalassemias are attributable to deficient synthesis of beta-globin and accumulation of unpaired alpha-chains. Stimulation of fetal globin synthesis is one strategy to correct the globin chain imbalance. There is evidence that Epo could play this role. In a mouse model of beta-thalassemia, an adeno-associated vector expressing the Epo cDNA was injected intramuscularly. Epo was secreted continuously during at least 1 yr. Erythropoiesis was improved in those mice by increasing the synthesis of fetal hemoglobin.
Sustained Remission of Metastatic Merkel Cell Carcinoma with Treatment of HIV Infection
Authors: Jedidiah Burack, Eric Lewin Altschuler
Journal: Journal of the Royal Society of Medicine (2003)

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer of presumed neuroendocrine origin. 1 The prognosis for metastatic MCC is typically very poor, despite treatment.2
Immunology of Human Immunodeficiency Virus Infection and the Acquired Immunodeficiency Syndrome
Authors: MAXIME SELIGMANN
Journal: Annals of Internal Medicine (1987)

Recent advances in the understanding of the pathogenesis of infection with human immunodeficiency virus (HIV) stems from the demonstration that the membrane glycoprotein, CD4, is the cellular receptor for HIV. This glycoprotein is found mainly on the surface of a major subpopulation of T lymphocytes and also on macrophages, natural killer cells, some B lymphocytes, and neuronal cells. Cells infected with HIV may be destroyed or have their normal function impaired. Host immune responses to HIV are poor and are not sustained. Neutralizing antibody often is not produced, or HIV may escape from normal immunosuppressive mechanisms through the process of rapid antigenic variation. Factors and markers that may be important in the outcome or that may predict progression of HIV infection are genetic (Gc type), environmental (nutritional status or intercurrent sexually transmitted diseases sustained by the host), and immunologic (rate of decline in number and impairment of function of CD4 + lymphocytes and of decline in antibody titers to HIV core protein, p24). A recombinant vaccine will probably be developed for testing in future clinical trials.
Diabetes and the Risk of Acute Urinary Tract Infection Among Postmenopausal Women
Authors: Edward J. Boyko, Stephan D. Fihn, Delia Scholes, Chi-Ling Chen, Esther H. Normand, Patricia Yarbro
Journal: Diabetes Care (2002)

OBJECTIVE—To examine whether the presence of diabetes alters the risk of acute urinary tract infection (UTI) in postmenopausal women. RESEARCH DESIGN AND METHODS—A case-control study of the Group Health Cooperative of Puget Sound (GHC), a staff-model nonprofit health maintenance organization in Washington State, was conducted. Subjects were women aged 55–75 years who had been members of GHC for at least 1 year and who had had an acute symptomatic UTI within the preceding month. Laboratory files were used to identify women with a urine culture that grew ≥105 colonies of a urinary pathogen. Medical records were reviewed to confirm the presence of acute, clinically symptomatic UTI. Control subjects were randomly selected from the GHC enrollment file, screened to remove women with recent UTI, and frequency matched to cases by age within 2 years. An interviewer ascertained self-reported clinician-diagnosed diabetes. Diagnosis of diabetes was confirmed by the GHC diabetes registry. A subsample of women underwent measurement of postvoid residual bladder volume (n = 748) and culture of vaginal flora (n = 454). RESULTS—Of the 901 case and 913 control subjects, diabetes was reported in 13.1 and 6.8%, respectively. The health plan diabetes registry confirmed the diagnosis in 92% of women who self-reported the condition. The age-adjusted odds ratio (OR) for UTI in relation to self-reported clinician-diagnosed diabetes was 2.2 (95% CI 1.6–3.0). Adjustment for frequency of sexual intercourse and history of UTI had little effect on this estimate. Compared with nondiabetic women, higher UTI odds were seen in subjects who used oral hypoglycemic agents (OR 2.9 [95% CI 1.7–5.1]) and insulin (2.6 [1.5–4.6]) but not in subjects with untreated diabetes or diabetes treated by lifestyle changes (1.3 [0.7–2.3]). No significant difference was seen in the OR for UTI in diabetic women with disease of shorter duration (&amp;lt;10 years, OR 1.9) or longer duration (≥10 years, OR 2.6) or in relation to HbA1c level. Similar microbiologic pathogens were seen in diabetic and nondiabetic women. No significant differences were seen by diabetes status in mean postvoid residual bladder volume or vaginal flora. CONCLUSIONS—Diabetes under pharmacologic treatment is associated with increased risk of clinically apparent UTI in postmenopausal women.
Fine-tuning DNA/albumin polyelectrolyte interactions to produce the efficient transfection agent cBSA-147
Authors: Klaus Eisele, Radu A. Gropeanu, Christoph M. Zehendner, Ali Rouhanipour, Arvind Ramanathan, George Mihov, Kalojan Koynov, Christoph R.W. Kuhlmann, Subhash G. Vasudevan, Heiko J. Luhmann, Tanja Weil
Journal: Biomaterials (2010)