tbuckley/cabot-search huggingface dataset:
Connecting Vascular and Nervous System Development: Angiogenesis and the Blood-Brain Barrier
Authors: Stephen J. Tam, Ryan J. Watts
Journal: Annual Review of Neuroscience (2010)

The vascular and nervous systems share a common necessity of circuit formation to coordinate nutrient and information transfer, respectively. Shared developmental principles have evolved to orchestrate the formation of both the vascular and the nervous systems. This evolution is highlighted by the identification of specific guidance cues that direct both systems to their target tissues. In addition to sharing cellular and molecular signaling events during development, the vascular and nervous systems also form an intricate interface within the central nervous system called the neurovascular unit. Understanding how the neurovascular unit develops and functions, and more specifically how the blood-brain barrier within this unit is established, is of utmost importance. We explore the history, recent discoveries, and unanswered questions surrounding the relationship between the vascular and nervous systems with a focus on developmental signaling cues that guide network formation and establish the interface between these two systems.
Determination of coronary collateral flow by a load line analysis.
Authors: D Wyatt, J Lee, J M Downey
Journal: Circulation Research (1982)

We have examined the feasibility of determining coronary collateral blood flow in an open-chest dog by a "load line" type of analysis as is often employed to analyze transistors and vacuum tubes. The load line equation states that collateral flow is given by the quantity: [Formula: see text] where PcP is peripheral coronary pressure, AOP is aortic pressure, Qret is retrograde flow, and K is a constant. The validity of this equation was critically tested in a series of dog experiments in which the collateral vessels were found to approximate a linear resistance, the source pressure for the collaterals (K in the equation) was found to be 0.8 of aortic pressure, and the retrograde flow with zero back pressure was found to account for all of the collateral flow. Finally, we found that estimates from the equation correlated well with direct microsphere measurements of collateral flow. All of these findings support the use of the proposed technique which determines collateral flow by three easily measured laboratory parameters.
BACE1-/- mice exhibit seizure activity that does not correlate with sodium channel level or axonal localization
Authors: Brian D Hitt, Thomas C Jaramillo, Dane M Chetkovich, Robert Vassar
Journal: Molecular Neurodegeneration (2010)

BACE1 is a key enzyme in the generation of the Abeta peptide that plays a central role in the pathogenesis of Alzheimer's disease. While BACE1 is an attractive therapeutic target, its normal physiological function remains largely unknown. Examination of BACE1-/- mice can provide insight into this function and also help anticipate consequences of BACE1 inhibition. Here we report a seizure-susceptibility phenotype that we have identified and characterized in BACE1-/- mice.We find that electroencephalographic recordings reveal epileptiform abnormalities in some BACE1-/- mice, occasionally including generalized tonic-clonic and absence seizures. In addition, we find that kainic acid injection induces seizures of greater severity in BACE1-/- mice relative to BACE1+/+ littermates, and causes excitotoxic cell death in a subset of BACE1-/- mice. This hyperexcitability phenotype is variable and appears to be manifest in approximately 30% of BACE1-/- mice. Finally, examination of the expression and localization of the voltage-gated sodium channel alpha-subunit Nav1.2 reveals no correlation with BACE1 genotype or any measure of seizure susceptibility.Our data indicate that BACE1 deficiency predisposes mice to spontaneous and pharmacologically-induced seizure activity. This finding has implications for the development of safe therapeutic strategies for reducing Abeta levels in Alzheimer's disease. Further, we demonstrate that altered sodium channel expression and axonal localization are insufficient to account for the observed effect, warranting investigation of alternative mechanisms.
Randomised controlled trial of self management leaflets and booklets for minor illness provided by post
Authors: P. Little
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To assess the effectiveness of providing information by post about managing minor illnesses. <b>Design:</b> Randomised controlled trial. <b>Setting:</b> Six general practices. <b>Participants:</b> Random sample of 4002 patients from the practice registers. <b>Intervention:</b> Patients were randomised to receive one of three kinds of leaflet or booklet endorsed by their general practitioner: control (surgery access times), booklet, or summary card. <b>Main outcome measures:</b> Attendance with the 42 minor illnesses listed in the booklet. Perceived usefulness of leaflets or booklets, confidence in managing illness, and willingness to wait before seeing the doctor. <b>Results:</b> 238 (6%) patients did not receive the intervention as allocated. Of the remaining 3764 patients, 2965 (79%) had notes available for review after one year. Compared with the control group, fewer patients attended commonly with the minor illnesses in the booklet group (≥2 consultations a year: odds ratio 0.81, 95% confidence interval 0.67 to 0.99) and the summary card group (0.83; 0.72 to 0.96). Among patients who had attended with respiratory tract infections in the past year there was a reduction in those attending in the booklet group (0.81; 0.62 to 1.07) and summary card group (0.67; 0.51 to 0.89) compared with the control group. The incidence of contacts with minor illness fell slightly compared with the previous year in the booklet (incidence ratio 0.97; 0.84 to 1.13) and summary card groups (0.93; 0.80 to 1.07). More patients in the intervention groups felt greater confidence in managing illness (booklet 32%, card 34%, control 12%, P&lt;0.001), but there was no difference in willingness to wait score (all groups mean=32, P=0.67). <b>Conclusion:</b> Most patients find information about minor illness provided by post useful, and it helps their confidence in managing illness. Information may reduce the number attending commonly with minor illness, but the effect on overall contacts is likely to be modest. These data suggest that posting detailed information booklets about minor illness to the general population would have a limited effect. <h3>What is already known on this topic</h3> Increasing attendance for minor illness in primary care is a threat to consultation time and quality of care Few recent studies have examined the effect of providing patients with information on self management of minor illness <h3>What this study adds</h3> Most patients find information about minor illness provided by post useful, and it helps their confidence in managing illness Information booklets and leaflets reduced the number attending frequently with minor illness, but the effect on overall contacts was not significant Information booklets on minor illness provided by post may have a limited role in the NHS
Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial
Authors: Susan P Buchbinder, Devan V Mehrotra, Ann Duerr, Daniel W Fitzgerald, Robin Mogg, David Li, Peter B Gilbert, Javier R Lama, Michael Marmor, Carlos del Rio, M Juliana McElrath, Danilo R Casimiro, Keith M Gottesdiener, Jeffrey A Chodakewitz, Lawrence Corey, Michael N Robertson
Journal: The Lancet (2008)
Romiplostim or Standard of Care in Patients with Immune Thrombocytopenia
Authors: David J. Kuter, Mathias Rummel, Ralph Boccia, B. Gail Macik, Ingrid Pabinger, Dominik Selleslag, Francesco Rodeghiero, Beng H. Chong, Xuena Wang, Dietmar P. Berger
Journal: New England Journal of Medicine (2010)

Romiplostim, a thrombopoietin mimetic, increases platelet counts in patients with immune thrombocytopenia, with few adverse effects.In this open-label, 52-week study, we randomly assigned 234 adult patients with immune thrombocytopenia, who had not undergone splenectomy, to receive the standard of care (77 patients) or weekly subcutaneous injections of romiplostim (157 patients). Primary end points were incidences of treatment failure and splenectomy. Secondary end points included the rate of a platelet response (a platelet count >50×10(9) per liter at any scheduled visit), safety outcomes, and the quality of life.The rate of a platelet response in the romiplostim group was 2.3 times that in the standard-of-care group (95% confidence interval [CI], 2.0 to 2.6; P<0.001). Patients receiving romiplostim had a significantly lower incidence of treatment failure (18 of 157 patients [11%]) than those receiving the standard of care (23 of 77 patients [30%], P<0.001) (odds ratio with romiplostim, 0.31; 95% CI, 0.15 to 0.61). Splenectomy also was performed less frequently in patients receiving romiplostim (14 of 157 patients [9%]) than in those receiving the standard of care (28 of 77 patients [36%], P<0.001) (odds ratio, 0.17; 95% CI, 0.08 to 0.35). The romiplostim group had a lower rate of bleeding events, fewer blood transfusions, and greater improvements in the quality of life than the standard-of-care group. Serious adverse events occurred in 23% of patients (35 of 154) receiving romiplostim and 37% of patients (28 of 75) receiving the standard of care.Patients treated with romiplostim had a higher rate of a platelet response, lower incidence of treatment failure and splenectomy, less bleeding and fewer blood transfusions, and a higher quality of life than patients treated with the standard of care. ( ClinicalTrials.gov number, NCT00415532.).
Interactions Between Gut Microbiota and Host Metabolism Predisposing to Obesity and Diabetes
Authors: Giovanni Musso, Roberto Gambino, Maurizio Cassader
Journal: Annual Review of Medicine (2010)

Novel, culture-independent, molecular and metagenomic techniques have provided new insight into the complex interactions between the mammalian host and gut microbial species. It is increasingly evident that gut microbes may shape the host metabolic and immune network activity and ultimately influence the development of obesity and diabetes. We discuss the evidence connecting gut microflora to obesity and to type 1 and type 2 diabetes, and we present recent insights into potential mechanisms underlying this relationship: increased nutrient absorption from the diet, prolonged intestinal transit time, altered bile acid entero-hepatic cycle, increased cellular uptake of circulating triglycerides, enhanced de novo lipogenesis, reduced free fatty acid oxidation, altered tissue composition of biologically active polyunsaturated fatty acid, chronic low-grade inflammation triggered by the endotoxin toll-like receptor 4 axis, and altered intestinal barrier function.
Severe pulmonary hypertension reversed by antibiotics in a patient with Whipple's disease
Authors: H. Riemer, R. Hainz, C. Stain, G. Dekan, M. Feldner-Busztin, P. Schenk, C. Muller, K. Sertl, O. C. Burghuber
Journal: Thorax (1997)

The case is described of a 58 year old man with systemic Whipple9s disease with pericardial and pleural effusions and severe pulmonary hypertension. After three months of antibiotic treatment there was a complete resolution, not only of the symptoms known to be associated with Whipple9s disease (diarrhoea, arthralgia, pericardial and pleural effusions), but also of pulmonary hypertension.
The Association Between Fractional Exhaled Nitric Oxide (FeNO) and Allergic Diseases and Asthma at Age Six Years in a High Risk Birth Cohort
Authors: C VIRNIG, D JACKSON, M EVANS, E ANDERSON, L SALAZARSR, D DASILVA, R KELLEY, T PAPPAS, K ROBERG, C TISLER
Journal: Journal of Allergy and Clinical Immunology (2008)
Mortality From Lymphohematopoietic Malignancies Among Workers in Formaldehyde Industries: The National Cancer Institute Cohort
Authors: Laura E. Beane Freeman, Aaron Blair, Jay H. Lubin, Patricia A. Stewart, Richard B. Hayes, Robert N. Hoover, Michael Hauptmann
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundFormaldehyde exposure is associated with leukemia in some epidemiological studies. In the National Cancer Institute's formaldehyde cohort, previously followed through December 31, 1979, and updated through December 31, 1994, formaldehyde exposure was associated with an increased risk for leukemia, particularly myeloid leukemia, that increased with peak and average intensity of exposure.
Severe oropharyngeal deglutition abnormalities in a patient with systemic sclerosis, managed with a gastrostomy
Authors: J. Stainforth, M.D.I. Goodfield
Journal: British Journal of Dermatology (1994)

Journal Article Severe oropharyngeal deglutition abnormalities in a patient with systemic sclerosis, managed with a gastrostomy Get access J. Stainforth, J. Stainforth Department of Dermatology, The General Infirmary, Great George Street, Leeds LSI EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.D.I. Goodfield M.D.I. Goodfield Department of Dermatology, The General Infirmary, Great George Street, Leeds LSI EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 5, 1 May 1994, Pages 682–683, https://doi.org/10.1111/j.1365-2133.1994.tb13124.x Published: 01 May 1994
LATE RESULTS OF ORBITAL UNDERCUTTING
Authors: WILLIAM BEECHER SCOVILLE
Journal: American Journal of Psychiatry (1960)

1. Psychosurgery continues to have definite applications, especially in the involutional and cyclic depressions, the agitated states of the elderly, the better preserved schizophrenics, and the intractable psychoneuroses, especially when suffering from anxiety or tension. 2. It is preferred to shock treatment in those depressions requiring more than short courses of shock treatment because of less emotional blunting, memory loss and relapses. 3. Agitated depressed senile states react more favorably to limited lobotomy operations than those in the younger age group. 4. Complete lobotomy has been replaced by limited selective operations. Undercutting of the orbital cortex offers the advantage of a precise technique under direct vision in an area causing appreciable lift in mood, lessening of anxiety and a minimum personality blunting. 5. The late results in orbital undercutting when studied in the separate categories of depressions, agitated senile states, schizophrenia, pseudoneurotic schizophrenia and intractable psychoneurosis have in most cases continued to show an improvement rather than regression or relapse. It has done so to a far greater degree than was anticipated, especially in schizophrenic patients of high cultural background. 6. Complications, including seizure formation, occur in the early rather than the late follow-up studies.
Receiver Operating Characteristic Analysis of HLA, CTLA4, and Insulin Genotypes for Type 1 Diabetes
Authors: Ana M. Valdes, Michael D. Varney, Henry A. Erlich, Janelle A. Noble
Journal: Diabetes Care (2013)

This study assessed the ability to distinguish between type 1 diabetes-affected individuals and their unaffected relatives using HLA and single nucleotide polymorphism (SNP) genotypes.Eight models, ranging from only the high-risk DR3/DR4 genotype to all significantly associated HLA genotypes and two SNPs mapping to the cytotoxic T-cell-associated antigen-4 gene (CTLA4) and insulin (INS) genes, were fitted to high-resolution class I and class II HLA genotyping data for patients from the Type 1 Diabetes Genetics Consortium collection. Pairs of affected individuals and their unaffected siblings were divided into a "discovery" (n = 1,015 pairs) and a "validation" set (n = 318 pairs). The discriminating performance of various combinations of genetic information was estimated using receiver operating characteristic (ROC) curve analysis.The use of only the presence or absence of the high-risk DR3/DR4 genotype achieved very modest discriminating ability, yielding an area under the curve (AUC) of 0.62 in the discovery set and 0.59 in the validation set. The full model-which included HLA information from the class II loci DPB1, DRB1, and DQB1; selected alleles from HLA class I loci A and B; and SNPs from the CTLA4 and INS genes-increased the AUC to 0.74 in the discovery set and to 0.71 in the validation set. A cost-effective alternative is proposed, using genotype information equivalent to typing four SNPs (DR3, DR4-DQB1*03:02, CTLA-4, and INS), which achieved an AUC of 0.72 in the discovery set and 0.69 in the validation set.Genotyping data sufficient to tag DR3, DR4-DQB1*03:02, CTLA4, and INS were shown to distinguish between subjects with type 1 diabetes and their unaffected siblings adequately to achieve clinically utility to identify children in multiplex families to be considered for early intervention.
Modelling survival in cystic fibrosis
Authors: M COREY
Journal: Thorax (2001)

The mantra of improving survival permeates virtually every paper related to prognosis or treatment for cystic fibrosis (CF) in the past two decades. However, the upward trend in the expected duration of life for patients with CF may have lost its momentum. The US and Canadian national CF registries show estimated median survival age increasing to around 32 years in 1989 and 1996, respectively, but in subsequent years no further improvement is seen.1 2Although the timing of a plateau in median survival age may differ, consistent patterns are seen in several other population based studies.3-5 An impressive reduction in infant and childhood CF mortality is almost universal, but projections for these rescued children as they move through adolescence and adulthood cannot be simply …
PI(3)King Apart PTEN's Role in Cancer
Authors: Siyuan Zhang, Dihua Yu
Journal: Clinical Cancer Research (2010)

The tumor suppressor phosphatase and tensin homolog (PTEN) is a nonredundant phosphatase, counteracting one of the most critical cancer-promoting pathways: the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. In addition to the canonical function of dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate (PIP3), recent studies showed the intriguing roles of PTEN in regulating genomic instability, DNA repair, stem cell self-renewal, cellular senescence, and cell migration and/or metastasis. Clinically, PTEN mutations and deficiencies are prevalent in many types of human cancers. Severe PTEN deficiency is also associated with advanced tumor stage and therapeutic resistance, such as the resistance to trastuzumab, an anti-HER2 therapy. Currently, targeting the deregulated PI3K/PTEN-Akt signaling axis has emerged as one of the major tenets in anticancer drug development. In this review, we highlight our current knowledge of PTEN function and the recent discoveries in dissecting the PTEN signaling pathway. The deregulations of PTEN in cancers, clinical lessons, and new prospects of rationally designed PI3K/Akt-targeted therapy for effective cancer treatment are also discussed.
Regional Myocardial Blood Flow Redistribution as a Cause of Postprandial Angina Pectoris
Authors: Ragavendra R. Baliga, Stuart D. Rosen, Paolo G. Camici, Jaspal S. Kooner
Journal: Circulation (1998)

Background —Postprandial angina pectoris has been recognized for more than two centuries and can be identified in up to 10% of patients with chronic ischemic heart disease. Redistribution of myocardial blood flow, from a region supplied by a severely stenotic coronary artery to those supplied by less diseased or normal vessels, is a potential mechanism of postprandial angina. Methods and Results —To test this hypothesis, we have determined the effects of a standard liquid meal on whole heart and regional myocardial blood flow, measured by means of dynamic positron emission tomography (PET) with 15 O-labeled water in 14 patients with a reproducible history of postprandial angina and 7 matched control subjects. The standard liquid meal precipitated angina pectoris in all patients. Baseline whole heart blood flow was similar and increased normally after the meal in patients (0.97±0.14 to 1.14±0.25 mL · min −1 · g −1 , P &lt;.04) as in control subjects (0.92±0.12 to 1.02±0.13 mL · min −1 · g −1 , P &lt;.02). In contrast, the coefficient of variation of blood flow increased significantly after the standard liquid meal in patients (34±9%, P &lt;.05 versus baseline) but not in control subjects (17±7%, P =NS versus baseline). In patients, analysis of regional myocardial blood flow demonstrated decreased myocardial blood flow in territories supplied by stenotic arteries (1.01±0.35 to 0.76±0.27 mL · min −1 · g −1 , P &lt;.03), but there was an increase in blood flow in territories supplied by normal arteries (0.89±0.16 to 1.34±0.25 mL · min −1 · g −1 , P &lt;.001) after the meal. Conclusions —The standard liquid meal induced angina pectoris in patients with coronary artery disease. Although whole heart blood flow increased appropriately for the greater cardiac work, there was a redistribution of regional blood flow from territories supplied by severely stenosed coronary arteries to those supplied by less diseased or normal arteries. This redistribution may be the cause of myocardial ischemia in postprandial angina.
Linkage analysis between loci in the renin-angiotensin axis and end-stage renal disease in African Americans.
Authors: H Yu, D W Bowden, B J Spray, S S Rich, B I Freedman
Journal: Journal of the American Society of Nephrology (1996)

The factors that initiate chronic renal failure in patients with hypertension, diabetes mellitus, and chronic glomerular disease are largely unknown. The likely genetic contribution to ESRD, particularly in African Americans, suggests that linkage analysis may be useful to evaluate the role of candidate genes in the pathogenesis of chronic renal failure. The renin-angiotensin-aldosterone (RAA) axis has been intensively evaluated for its contribution to cardiovascular disease and nephropathy. This study tested for linkage between candidate genes in the RAA axis and chronic renal failure, using 85 African-American sibling pairs (from 65 families) concordant for ESRD. Angiotensinogen was selected because of the putative link between it and mild to moderate essential hypertension and nephrosclerosis; angiotensin-converting enzyme because of its possible contribution to diabetic nephropathy; and renin, the angiotensin II receptor, and kallikrein because of their roles in hypertension and renal perfusion. These candidate loci did not demonstrate linkage to either diabetic or nondiabetic renal disease in this study's collection of sibling pairs. These results suggest that polymorphisms at these RAA axis loci do not make major contributions to the pathogenesis of renal disease in African Americans.
Anthramine Carcinogenesis in the Skin of Rats. I. The Epidermis<xref ref-type="fn" rid="FN2">2</xref>
Authors: Richard L. Dobson, M.D.
Journal: JNCI Journal of the National Cancer Institute (1963)

Repeated application of 2-anthramine to the skin of rats produced mainly basal cell epitheliomas and some squamous cell carcinomas. Both tumors arose from the stratum germinativum of the epidermis. The evolution of the basal cell tumors appeared consistently correlated with the condition of the underlying dermis. If the basement membrane of the epidermis was intact, only intraepidermal tumors resulted. With disruption of the basement membrane, downward proliferation of nests of basal cells occurred. Proliferation progressed until normal connective tissue was encountered. Organized stromal elements formed in relation to the epithelial masses which differentiated, forming a caricature of the pilary apparatus. The squamous cell epithelioma, did not appear to participate in such a relationship. The difference in the malignant potentialities of basal and squamous cell epitheliomas may reflect the response or lack of response of these tumors to factors associated with connective tissue.