tbuckley/cabot-search huggingface dataset:
Pressure-induced vasoconstriction of renal microvessels in normotensive and hypertensive rats. Studies in the isolated perfused hydronephrotic kidney.
Authors: K Hayashi, M Epstein, R Loutzenhiser
Journal: Circulation Research (1989)

The capacity of small arteries to respond to increased intravascular pressure may be altered in hypertension. In the kidney, hypertension is associated with a compensatory shift in the autoregulatory response to pressure. To directly determine the effects of established hypertension on the renal microvascular response to changes of perfusion pressure, we evaluated pressure-induced vasoconstriction in hydronephrotic kidneys isolated from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Vessel diameters of interlobular arteries (ILAs) and afferent and efferent arterioles were determined by computer-assisted videomicroscopy during alterations in renal arterial pressure (RAP) from 80 to 180 mm Hg. Increased RAP induced a pressure-dependent vasoconstriction in preglomerular vessels (afferent arterioles and ILAs), but not in postglomerular vessels (efferent arterioles). The calcium antagonist nifedipine prevented pressure-induced afferent arteriolar vasoconstriction with a similar half-maximal inhibitory concentration (IC50) (WKY, 63 +/- 27 vs. SHR, 60 +/- 32 nM). The pressure-activation curves for ILAs in SHR and WKY were similar. In contrast, the pressure-activation curve for afferent arterioles in SHR kidneys exhibited a rightward shift, which was observed at every segment of the afferent arteriole (i.e., near ILA, at midportion, and near glomerulus). These findings demonstrate that the ILA and the afferent arteriole both possess the ability to constrict in response to increased pressure, whereas this property is lacking in the efferent arteriole. Hypertension was associated with a compensatory shift in the pressure response of the afferent arteriole, such that higher RAPs were required to elicit vasoconstriction in this vessel.
Cytochrome P450, CYP26AI, is expressed at low levels in human epidermal keratinocytes and is not retinoic acid-inducible
Authors: None Popa, None Dicker, None Dahler, None Saunders
Journal: British Journal of Dermatology (1999)

Journal Article Cytochrome P450, CYP26AI, is expressed at low levels in human epidermal keratinocytes and is not retinoic acid‐inducible Get access C. Popa, C. Popa Epithelial Pathobiology Group, Centre for Immunology and Cancer Research, University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia Search for other works by this author on: Oxford Academic Google Scholar A.J. Dicker, A.J. Dicker Epithelial Pathobiology Group, Centre for Immunology and Cancer Research, University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia Search for other works by this author on: Oxford Academic Google Scholar A.L. Dahler, A.L. Dahler Epithelial Pathobiology Group, Centre for Immunology and Cancer Research, University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia Search for other works by this author on: Oxford Academic Google Scholar N.A. Saunders N.A. Saunders Epithelial Pathobiology Group, Centre for Immunology and Cancer Research, University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia Nicholas Saunders E‐mail: NSaunders@medicine. pa.uq.edu.au Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 3, 1 September 1999, Pages 460–468, https://doi.org/10.1046/j.1365-2133.1999.03039.x Published: 01 September 1999
Delayed Psychosomatic Skin Disorders
Authors: Robert Richards
Journal: British Journal of Dermatology (1971)

Journal Article Delayed Psychosomatic Skin Disorders Get access Robert Richards Robert Richards 170 St. George Street, Suite 206, Toronto 5, Ontario, Canada Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 85, Issue 2, 1 August 1971, Page 196, https://doi.org/10.1111/j.1365-2133.1971.tb07213.x Published: 01 August 1971
Abstract 4229: Study on the germline mutation and protein expression of hMLH1 and hMSH2 gene in Chinese HNPCC probands.
Authors: Xia Sheng
Journal: Cancer Research (2013)

Abstract BACKGROUND&amp;AIMS: Compare with sporadic colorectal cancer (SCRC), Hereditary nonpolyposis colorectal cancer (HNPCC) shows its own characteristcs associated with the molecular mechanism,clinical features,the methods for treatment and management of HNPCC kindreds. The molecular genetics basis of HNPCC was the mutation of mismatch repair (MMR) gene. Some HNPCC families which can found the mutation of MMR gene didn't fulfil any clinical criteria while more than fifty percent suspected HNPCC patients can't found mutation of MMR gene. Therefore, the tumorigenesis of HNPCC must be associated with other disease genes which have not been credited. The expression of hMLH1 and hMSH2 protein in 50 HNPCC probands fulfilling defferent clinical criteria and the germline mutation of hMLH1 and hMSH2 gene in 26 probands were analysed. Methods: The peripheral blood was collected from the probands of 26 HNPCC families fulfilling different clinical criterial, of which 7 families fulfilled AC, 19 kindreds fit BG. Genomic DNA was extracted following the manafacturer's protocol and used as the template to amplify 35 exons of the 2 genes by PCR. PCR products were purified and used as the template for direct DNA sequencing. The results of sequencing were analysed by different bioanalysis software. To further investigate the pathological effects of detected missense mutations, we analyse the same exon of hPMS2 gene using PCR-based sequencing in 130 healthy persons without family history. IHC envision two step method was performed.Results: 8 germline mutation of hMLH1 and hMSH2 was found in 26 HNPCC probands families. 4 fulfilled AC and 4 fulfilled BG..17 probands was found to be hMLH1 and hMSH2 protein deficient. Conclusion: The rate of germline mutation and protein expression was 30.8% and 34%. AC are the most sensitve clinical creteria to predict mutations. Immunohistochemical staining are reliable screening method with high predictive value for the detection of mutation. Some suspected HNPCC patients can't found mutation of MMR gene. Citation Format: Xia Sheng. Study on the germline mutation and protein expression of hMLH1 and hMSH2 gene in Chinese HNPCC probands. [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 4229. doi:10.1158/1538-7445.AM2013-4229
Evaluating Many Treatments and Biomarkers in Oncology: A New Design
Authors: Richard Kaplan, Timothy Maughan, Angela Crook, David Fisher, Richard Wilson, Louise Brown, Mahesh Parmar
Journal: Journal of Clinical Oncology (2013)

There is a pressing need for more-efficient trial designs for biomarker-stratified clinical trials. We suggest a new approach to trial design that links novel treatment evaluation with the concurrent evaluation of a biomarker within a confirmatory phase II/III trial setting. We describe a new protocol using this approach in advanced colorectal cancer called FOCUS4. The protocol will ultimately answer three research questions for a number of treatments and biomarkers: (1) After a period of first-line chemotherapy, do targeted novel therapies provide signals of activity in different biomarker-defined populations? (2) If so, do these definitively improve outcomes? (3) Is evidence of activity restricted to the biomarker-defined groups? The protocol randomizes novel agents against placebo concurrently across a number of different biomarker-defined population-enriched cohorts: BRAF mutation; activated AKT pathway: PI3K mutation/absolute PTEN loss tumors; KRAS and NRAS mutations; and wild type at all the mentioned genes. Within each biomarker-defined population, the trial uses a multistaged approach with flexibility to adapt in response to planned interim analyses for lack of activity. FOCUS4 is the first test of a protocol that assigns all patients with metastatic colorectal cancer to one of a number of parallel population-enriched, biomarker-stratified randomized trials. Using this approach allows questions regarding efficacy and safety of multiple novel therapies to be answered in a relatively quick and efficient manner, while also allowing for the assessment of biomarkers to help target treatment.
Pseudomonas aeruginosa in patients hospitalised for COPD exacerbation: a prospective study
Authors: C. Garcia-Vidal, P. Almagro, V. Romaní, M. Rodríguez-Carballeira, E. Cuchi, L. Canales, D. Blasco, J. L. Heredia, J. Garau
Journal: European Respiratory Journal (2009)

Risk factors for Pseudomonas aeruginosa (PA) isolation in patients hospitalised for chronic obstructive pulmonary disease (COPD) exacerbation remain controversial. The aim of our study was to determine the incidence and risk factors for PA isolation in sputum at hospital admission in a prospective cohort of patients with acute exacerbation of COPD. We prospectively studied all patients with COPD exacerbation admitted to our hospital between June 2003 and September 2004. Suspected predictors of PA isolation were studied. Spirometry tests and 6-min walking tests were performed 1 month after the patients were discharged. High-resolution computed tomography (HRCT) was performed in a randomised manner in one out of every two patients to quantify the presence and extent of bronchiectasis. Patients were followed up during the following year for hospital re-admissions. A total of 188 patients were included, of whom 31 (16.5%) had PA in sputum at initial admission. The BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index (OR 2.18, CI 95% 1.26-3.78; p = 0.005), admissions in the previous year (OR 1.65, CI 95% 1.13-2.43; p = 0.005), systemic steroid treatment (OR 14.7, CI 95% 2.28-94.8; p = 0.01), and previous isolation of PA (OR 23.1, CI 95% 5.7-94.3; p<0.001) were associated with PA isolation. No relationship was seen between bronchiectasis in HRCT and antibiotic use in the previous 3 months. PA in sputum at hospital admission is more frequent in patients with poorer scoring on the BODE index, previous hospital admissions, oral corticosteroids and prior isolation of PA.
Head Injuries in General Practice
Authors: J. Fraser
Journal: BMJ (1937)

In a single surgical charge in the Edinburgh Royal Infirmary over the period of a year seventy cases of head injuries were admitted, 5.5 per cent. of the total admissions, and the -mortality was' 14.2 per cent.I have quoted these figures to show what is already known -that this type of injury is relatively common, increasingly so, and that it-is associated with a considerable risk to life.
Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis
Authors: M Boers
Journal: Annals of the Rheumatic Diseases (2003)

Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory.To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account.HDL cholesterol and total cholesterol levels were determined in:(a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial).In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity.In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.
Trastuzumab for Patients With Axillary-Node–Positive Breast Cancer: Results of the FNCLCC-PACS 04 Trial
Authors: Marc Spielmann, Henri Roché, Thierry Delozier, Jean-Luc Canon, Gilles Romieu, Hugues Bourgeois, Jean-Marc Extra, Daniel Serin, Pierre Kerbrat, Jean-Pascal Machiels, Alain Lortholary, Hubert Orfeuvre, Mario Campone, Anne-Claire Hardy-Bessard, Bruno Coudert, Marie Maerevoet, Gilles Piot, Andrew Kramar, Anne-Laure Martin, Frédérique Penault-Llorca
Journal: Journal of Clinical Oncology (2009)

To evaluate the efficacy of trastuzumab in patients with node-positive breast cancer treated with surgery, adjuvant chemotherapy, radiotherapy, and hormone therapy if applicable.Three thousand ten patients with operable node-positive breast cancer were randomly assigned to receive adjuvant anthracycline-based chemotherapy with or without docetaxel. Patients who presented human epidermal growth factor receptor 2 (HER2) -overexpressing tumors were secondary randomly assigned to either a sequential regimen of trastuzumab (6 mg/kg every 3 weeks) for 1 year or observation. The primary end point was disease-free survival (DFS).Overall 528 patients were randomly assigned between trastuzumab (n = 260) and observation (n = 268) arm. Of the 234 patients (90%) who received at least one administration of trastuzumab, 196 (84%) received at least 6 months of treatment, and 41 (18%) discontinued treatment due to cardiac events (any grade). At the date of analysis (October 2007), 129 DFS events were recorded. Random assignment to the trastuzumab arm was associated with a nonsignificant 14% reduction in the risk of relapse (hazard ratio, 0.86; 95% CI, 0.61 to 1.22; P = .41, log-rank stratified on pathologic node involvement). Three-year DFS rates were 78% (95% CI, 72.3 to 82.5) and 81% (95% CI, 75.3 to 85.4) in the observation and trastuzumab arms, respectively.After a 47-month median follow-up, 1 year of trastuzumab given sequentially after adjuvant chemotherapy was not associated with a statistically significant decrease in the risk of relapse.
Post-exposure prophylaxis against HIV infection is hard to supply for expatriate staff
Authors: A. Logie
Journal: BMJ (1998)

EDITOR —Gilks and Wilkinson raise important issues on nosocomial HIV infection.1 Healthcare workers planning to work overseas must be fully briefed about the risks of HIV infection and what to do. At the time of my own needlestick injury in 19932 I was reassured by the quoted risk of seroconversion of 0.3%. I did not know that my coeliac disease, along with other …
The effect of maternal child marriage on morbidity and mortality of children under 5 in India: cross sectional study of a nationally representative sample
Authors: Anita Raj, Niranjan Saggurti, Michael Winter, Alan Labonte, Michele R Decker, Donta Balaiah, Jay Glen Silverman
Journal: BMJ (2010)

<b>Objective</b> To assess associations between maternal child marriage (marriage before age 18) and morbidity and mortality of infants and children under 5 in India. <b>Design </b>Cross-sectional analyses of nationally representative household sample. Generalised estimating equation models constructed to assess associations. Adjusted models included maternal and child demographics and maternal body mass index as covariates. <b>Setting </b>India. <b>Population</b> Women aged 15-49 years (n=124 385); data collected in 2005-6 through National Family Health Survey-3. Data about child morbidity and mortality reported by participants. Analyses restricted to births in past five years reported by ever married women aged 15-24 years (n=19 302 births to 13 396 mothers). <b>Main outcome measures</b> In under 5s: mortality related infectious diseases in the past two weeks (acute respiratory infection, diarrhoea); malnutrition (stunting, wasting, underweight); infant (age &lt;1 year) and child (1-5 years) mortality; low birth weight (&lt;2500 kg). <b>Results </b>The majority of births (73%; 13 042/19 302) were to mothers married as minors. Although bivariate analyses showed significant associations between maternal child marriage and infant and child diarrhoea, malnutrition (stunted, wasted, underweight), low birth weight, and mortality, only stunting (adjusted odds ratio 1.22, 95% CI 1.12 to 1.33) and underweight (1.24, 1.14 to 1.36) remained significant in adjusted analyses. We noted no effect of maternal child marriage on health of boys versus girls. <b>Conclusions </b>The risk of malnutrition is higher in young children born to mothers married as minors than in those born to women married at a majority age. Further research should examine how early marriage affects food distribution and access for children in India.
Functional Consequence of Positive Selection Revealed through Rational Mutagenesis of Human Myeloperoxidase
Authors: Noeleen B. Loughran, Sara Hinde, Sally McCormick-Hill, Kevin G. Leidal, Sarah Bloomberg, Sinéad T. Loughran, Brendan O’Connor, Ciarán Ó'Fágáin, William M. Nauseef, Mary J. O’Connell
Journal: Molecular Biology and Evolution (2012)

Myeloperoxidase (MPO) is a member of the mammalian heme peroxidase (MHP) multigene family. Whereas all MHPs oxidize specific halides to generate the corresponding hypohalous acid, MPO is unique in its capacity to oxidize chloride at physiologic pH to produce hypochlorous acid (HOCl), a potent microbicide that contributes to neutrophil-mediated host defense against infection. We have previously resolved the evolutionary relationships in this functionally diverse multigene family and predicted in silico that positive Darwinian selection played a major role in the observed functional diversities (Loughran NB, O'Connor B, O'Fagain C, O'Connell MJ. 2008. The phylogeny of the mammalian heme peroxidases and the evolution of their diverse functions. BMC Evol Biol. 8:101). In this work, we have replaced positively selected residues asparagine 496 (N496), tyrosine 500 (Y500), and leucine 504 (L504) with the amino acids present in the ancestral MHP and have examined the effects on the structure, biosynthesis, and activity of MPO. Analysis in silico predicted that N496F, Y500F, or L504T would perturb hydrogen bonding in the heme pocket of MPO and thus disrupt the structural integrity of the enzyme. Biosynthesis of the mutants stably expressed in human embryonic kidney 293 cells yielded apoproMPO, the heme-free, enzymatically inactive precursor of MPO, that failed to undergo normal maturation or proteolytic processing. As a consequence of the maturational arrest at the apoproMPO stage of development, cells expressing MPO with mutations N496F, Y500F, L504T, individually or in combination, lacked normal peroxidase or chlorinating activity. Taken together, our data provide further support for the in silico predictions of positive selection and highlight the correlation between positive selection and functional divergence. Our data demonstrate that directly probing the functional importance of positive selection can provide important insights into understanding protein evolution.
REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR PRODUCTS
Authors: L. A. Julianelle, C. P. Rhoads
Journal: The Journal of Experimental Medicine (1932)

1. The intratracheal injection of egg albumin or pneumococcus protein induces an inflammatory reaction in the lungs of rabbits previously inoculated with the respective antigen. 2. A similar reaction occurs following intratracheal injection of pneumococcus protein into the lungs of rabbits previously inoculated with heat-killed suspensions of the bacteria. 3. This reaction appears to be related to the presence of circulating antibody and to have the nature of the Arthus reaction. 4. A study of the reaction of the lung of rabbits to infection caused by intravenous injections of Pneumococcus reveals that (a) reactions occur irregularly in the lung; (b) in the lungs in which reactions do occur, the histological changes are not different in normal rabbits and in rabbits made resistant by previous intravenous or intracutaneous injections of pneumococci. 5. Intratracheal injection of pneumococcus protein followed by intravenous injection of virulent pneumococci on the next day does not alter the course and character of the infection in resistant rabbits. 6. The experiments reported in this paper bring no evidences to support the view that the lesions in the lungs of rabbits following the intravenous injection of pneumococci are modified by any previous state of sensitivity.
Changes in Central Venous Pressure after Moderate Hemorrhage and Transfusion in Man
Authors: OTTO H. GAUER, JAMES P. HENRY, HERBERT O. SIEKER
Journal: Circulation Research (1956)

Changes in central venous pressure were recorded continuously before, during and for 40 to 50 minutes after hemorrhage and transfusion in the amounts of 6.5 cc. per Kg. and 8.1 cc. per Kg. The pressures obtained 15 to 20 minutes after onset of blood volume changes were independent of the rate of hemorrhage or transfusion. In the average subject of 70 Kg., Δ P /ΔV for zero time was 0.7 cm. of water pressure change per 100 cc. volume change. Recovery from hemorrhage was imperceptible during the one hour observation period, but recovery from transfusion was slightly faster.