tbuckley/cabot-search huggingface dataset:
Folate Transport Gene Inactivation in Mice Increases Sensitivity to Colon Carcinogenesis
Authors: David W.L. Ma, Richard H. Finnell, Laurie A. Davidson, Evelyn S. Callaway, Ofer Spiegelstein, Jorge A. Piedrahita, J. Michael Salbaum, Claudia Kappen, Brad R. Weeks, Jill James, Daniel Bozinov, Joanne R. Lupton, Robert S. Chapkin
Journal: Cancer Research (2005)

Low dietary folate intake is associated with an increased risk for colon cancer; however, relevant genetic animal models are lacking. We therefore investigated the effect of targeted ablation of two folate transport genes, folate binding protein 1 (Folbp1) and reduced folate carrier 1 (RFC1), on folate homeostasis to elucidate the molecular mechanisms of folate action on colonocyte cell proliferation, gene expression, and colon carcinogenesis. Targeted deletion of Folbp1 (Folbp1(+/-) and Folbp1(-/-)) significantly reduced (P < 0.05) colonic Folbp1 mRNA, colonic mucosa, and plasma folate concentration. In contrast, subtle changes in folate homeostasis resulted from targeted deletion of RFC1 (RFC1(+/-)). These animals had reduced (P < 0.05) colonic RFC1 mRNA and exhibited a 2-fold reduction in the plasma S-adenosylmethionine/S-adenosylhomocysteine. Folbp1(+/-) and Folbp1(-/-) mice had larger crypts expressed as greater (P < 0.05) numbers of cells per crypt column relative to Folbp1(+/+) mice. Colonic cell proliferation was increased in RFC1(+/-) mice relative to RFC1(+/+) mice. Microarray analysis of colonic mucosa showed distinct changes in gene expression specific to Folbp1 or RFC1 ablation. The effect of folate transporter gene ablation on colon carcinogenesis was evaluated 8 and 38 weeks post-azoxymethane injection in wild-type and heterozygous mice. Relative to RFC1(+/+) mice, RFC1(+/-) mice developed increased (P < 0.05) numbers of aberrant crypt foci at 8 weeks. At 38 weeks, RFC1(+/-) mice developed local inflammatory lesions with or without epithelial dysplasia as well as adenocarcinomas, which were larger relative to RFC1(+/+) mice. In contrast, Folbp1(+/-) mice developed 4-fold (P < 0.05) more lesions relative to Folbp1(+/+) mice. In conclusion, Folbp1 and RFC1 genetically modified mice exhibit distinct changes in colonocyte phenotype and therefore have utility as models to examine the role of folate homeostasis in colon cancer development.
Role of Parathyroid Hormone in the Downregulation of Liver Cytochrome P450 in Chronic Renal Failure
Authors: Josée Michaud, Judith Naud, Jéro[Combining Circumflex Accent]me Chouinard, Franc[COMBINING CEDILLA]ois Désy, Francois A. Leblond, Karine Desbiens, Alain Bonnardeaux, Vincent Pichette
Journal: Journal of the American Society of Nephrology (2006)

Chronic renal failure (CRF) is associated with a decrease in drug metabolism secondary to a decrease in liver cytochrome P450 (P450). The predominant theory to explain this decrease is the presence of factors in the blood of uremic patients. This study tested the hypothesis that parathyroid hormone (PTH) could be this factor. The objectives of this study were to determine (1) the role of PTH in the downregulation of hepatocyte P450 induced by rat uremic serum, (2) the role of PTH in the downregulation of liver P450 in rats with CRF, and (3) the effects of PTH on P450 in hepatocytes. For this purpose, (1) hepatocytes were incubated with serum from rat with CRF that was depleted with anti-PTH antibodies or with serum from parathyroidectomized (CRF-PTX) rat with CRF, (2) the effect of PTX on liver P450 was evaluated in rats with CRF, and (3) the effects of PTH on P450 in hepatocytes were determined. The depletion of PTH from CRF serum completely reversed the downregulating effect of CRF serum on P450 in hepatocytes. Addition of PTH (10(-9) M) to depleted CRF serum induced a decrease in P450 similar to nondepleted CRF serum. The serum of CRF-PTX rats had no effect on P450 in hepatocytes compared with CRF serum. Adding PTH to CRF-PTX serum induced a similar decrease in P450 as obtained with CRF serum. Finally, PTX prevented the decrease of liver P450 in rats with CRF. In summary, PTH is the major mediator implicated in the downregulation of liver P450 in rats with CRF.
Acquisition of <i>Helicobacter pylori</i> infection after outbreaks of gastroenteritis: prospective cohort survey in institutionalised young people
Authors: Rémi Laporte, Philippe Pernes, Pascale Pronnier, Frédéric Gottrand, Pascal Vincent
Journal: BMJ (2004)

The exact mode of spread of Helicobacter pylori is still unknown. Transmission during transit disorders of the gastrointestinal tract has been suggested, although there is no evidence to date of transmission during outbreaks of gastroenteritis.1–3 We determined whether gastroenteritis in young people infected with H pylori can lead to acquisition of the bacterium by peers.

Our study took place in a French institution for neurologically handicapped children and adolescents. The young people had been institutionalised for several years and resided across five housing sections (A to E). We included all 112 residents in May 2001. H pylori infection present at the outset of the study was detected by using the non-invasive HpSA stool antigen test (Meridian; 91% sensitivity and 93% specificity).4 Stool samples were stored and transported at 4°C within 48 hours and then frozen. The residents were monitored for one year. Events and clinical data …
Investigation of Complement Activation Product C4d as a Diagnostic and Prognostic Biomarker for Lung Cancer
Authors: Daniel Ajona, María J. Pajares, Leticia Corrales, Jose L. Perez-Gracia, Jackeline Agorreta, Maria D. Lozano, Wenceslao Torre, Pierre P. Massion, Juan P. de-Torres, Eloisa Jantus-Lewintre, Carlos Camps, Javier J. Zulueta, Luis M. Montuenga, Ruben Pio
Journal: JNCI Journal of the National Cancer Institute (2013)

There is a medical need for diagnostic biomarkers in lung cancer. We evaluated the diagnostic performance of complement activation fragments.We assessed complement activation in four bronchial epithelial and seven lung cancer cell lines. C4d, a degradation product of complement activation, was determined in 90 primary lung tumors; bronchoalveolar lavage supernatants from patients with lung cancer (n = 50) and nonmalignant respiratory diseases (n = 22); and plasma samples from advanced (n = 50) and early lung cancer patients (n = 84) subjects with inflammatory lung diseases (n = 133), and asymptomatic individuals enrolled in a lung cancer computed tomography screening program (n = 190). Two-sided P values were calculated by Mann-Whitney U test.Lung cancer cells activated the classical complement pathway mediated by C1q binding that was inhibited by phosphomonoesters. Survival was decreased in patients with high C4d deposition in tumors (hazard ratio [HR] = 3.06; 95% confidence interval [CI] = 1.18 to 7.91). C4d levels were increased in bronchoalveolar lavage fluid from lung cancer patients compared with patients with nonmalignant respiratory diseases (0.61 ± 0.87 vs 0.16 ± 0.11 µg/mL; P < .001). C4d levels in plasma samples from lung cancer patients at both advanced and early stages were also increased compared with control subjects (4.13 ± 2.02 vs 1.86 ± 0.95 µg/mL, P < 0.001; 3.18 ± 3.20 vs 1.13 ± 0.69 µg/mL, P < .001, respectively). C4d plasma levels were associated with shorter survival in patients at advanced (HR = 1.59; 95% CI = 0.97 to 2.60) and early stages (HR = 5.57; 95% CI = 1.60 to 19.39). Plasma C4d levels were reduced after surgical removal of lung tumors (P < .001) and were associated with increased lung cancer risk in asymptomatic individuals with (n = 32) or without lung cancer (n = 158) (odds ratio = 4.38; 95% CI = 1.61 to 11.93).Complement fragment C4d may serve as a biomarker for early diagnosis and prognosis of lung cancer.
Clinical and biological characteristics of Ureaplasma urealyticum induced polyarthritis in a patient with common variable hypogammaglobulinaemia.
Authors: R R Lehmer, B S Andrews, J A Robertson, E J Stanbridge, L de la Maza, G J Friou
Journal: Annals of the Rheumatic Diseases (1991)

Persistent infectious polyarthritis caused by Ureaplasma urealyticum in a patient with common variable hypogammaglobulinaemia is described. The patient developed a symmetrical, destructive polyarthritis and tenosynovitis associated with a markedly depressed synovial fluid glucose concentration and characteristic soft tissue abscesses. The ureaplasma organism developed resistance to multiple antibiotics and persisted for five years. The organism was identified repeatedly in many joints by culture, confirmed by DNA hybridisation, and mycoplasma-like structures were shown in synovial tissues by electron microscopy.
An Outbreak of Invasive Group A Streptococcal Disease Associated With High Carriage Rates of the Invasive Clone Among School-aged Children
Authors: Franklin R. Cockerill
Journal: JAMA (1997)

To determine if a common strain of group A streptococcus was responsible for an outbreak of invasive streptococcal disease in southeastern Minnesota and to determine whether this strain was prevalent among residents of this area during the outbreak who either had streptococcal pharyngitis or were asymptomatic streptococcal carriers.Pharyngeal culture survey and case-contact evaluation.Three adjacent counties in southeastern Minnesota defined as the outbreak area. Outbreak period, January 1 through March 31, 1995.Seven patients with invasive streptococcal infection, 1249 patients (adults and children) with sore throat who resided in the outbreak area, children from an elementary school located in 1 community where the majority of invasive cases occurred, and 896 students from 3 schools located in Minnesota counties outside the outbreak area.Pulsed-field gel electrophoresis (DNA fingerprinting) of group A streptococcal isolates obtained from patients with invasive disease, throat swabs of patients with sore throat, and throat swabs of asymptomatic school-aged children.All patients with outbreak-associated invasive disease had group A streptococcal isolates that were indistinguishable by pulsed-field gel electrophoresis. Additional testing showed that these isolates carried significant virulence factors including pyrogenic exotoxin A and streptococcal superantigen. Five of these 7 patients with invasive disease had underlying medical conditions; 4 developed toxic shock syndrome and died (case fatality, 57%). The outbreak-associated group A streptococcal clone was found in 69 (26.5%) of the 260 patients with sore throat from whom group A streptococcus was isolated. The frequency of the outbreak clone among pharyngeal carriers from the 3 schools outside the outbreak area was significantly less (range, 0%-10%) than in children from the school in the outbreak area (78%; relative risk, 29; 95% confidence interval, 11.1-78.1; P<.001). Four of the 7 patients with outbreak-associated disease had contact with children who attended the school in the outbreak area.A single clone of group A streptococcus was responsible for 7 cases of invasive streptococcal disease during an outbreak in Minnesota and for a significant number of pharyngitis cases that also occurred during the outbreak. Invasive disease occurred most frequently in persons with underlying medical conditions. This outbreak was also associated with increased carriage rates of the invasive streptococcal clone among community school-aged children. Cases of invasive group A streptococcal infection may therefore reflect the tip of the iceberg with regard to the burden of colonization of a specific invasive streptococcal clone in a community.
Overprescribing antidepressants: where's the evidence?
Authors: M. McCartney
Journal: BMJ (2014)

Is the United Kingdom in the grip of an antidepressants epidemic? We are certainly gripped by an epidemic of the media writing about them. The past few months have seen reports of more antidepressants being used during the financial crisis,1 stories of how many people seem to be taking them,2 and an article in the Guardian by Peter Gotzsche—a member of the newly formed Council for Evidence Based Psychiatry, which aims “To reduce psychiatric harm by communicating the latest evidence.”3

“It’s hard to believe that so many people have become mentally disturbed and that these prescription increases reflect a genuine need,” said Gotzsche. He blamed overdiagnosis, conflicts of interest among the writers of the Diagnostic …
Diffusion Tensor Imaging White Matter Endophenotypes in Patients With Schizophrenia or Psychotic Bipolar Disorder and Their Relatives
Authors: Pawel Skudlarski, David J. Schretlen, Gunvant K. Thaker, Michael C. Stevens, Matcheri S. Keshavan, John A. Sweeney, Carol A. Tamminga, Brett A. Clementz, Kasey O’Neil, Godfrey D. Pearlson
Journal: American Journal of Psychiatry (2013)

OBJECTIVE Both schizophrenia and bipolar disorder are hypothesized to involve disordered brain connectivity. Prior studies show low white matter integrity, measured with diffusion tensor imaging, for both disorders. The authors studied disease specificity and endophenotypic status of these abnormalities by examining patients and their unaffected relatives. METHOD The 513 participants included probands with schizophrenia, probands with psychotic bipolar disorder, their first-degree relatives, and healthy comparison subjects. Fractional anisotropy measures of white matter integrity were collected at two sites as a part of the Bipolar-Schizophrenia Network on Intermediate Phenotypes project. Relatives with cluster A or B personality characteristics were further examined. RESULTS Both the probands with schizophrenia and those with psychotic bipolar disorder showed lower fractional anisotropy than the comparison subjects in multiple white matter regions; differences were more marked in schizophrenia. No significant differences existed between proband groups, but in some brain regions scores on a measure of the dimensional continuum between schizophrenia and bipolar disorder, the Schizo-Bipolar Scale, showed correlations with fractional anisotropy. Many regions affected in schizophrenia probands showed similar but smaller effects in relatives, with a continuous fractional anisotropy decrease from healthy subjects to relatives to cluster A/B relatives to probands. The pattern for psychotic bipolar disorder was similar but involved fewer brain regions. Effects in bipolar relatives were limited to younger subjects. Fractional anisotropy decreased with age in all groups; this decrease was exaggerated in schizophrenia but not psychotic bipolar disorder. CONCLUSIONS Fractional anisotropy was highly heritable, supporting its value as a potential endophenotype.
Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis
Authors: C. J Haagsma, H. J Blom, P. L C M van Riel, M. A van't Hof, B. A J Giesendorf, D. van Oppenraaij-Emmerzaal, L. B A van de Putte
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To study the influence of sulphasalazine (SSZ), methotrexate (MTX), and the combination (COMBI) of both on plasma homocysteine and to study the relation between plasma homocysteine and their clinical effects. <h3>METHODS</h3> 105 patients with early rheumatoid arthritis (RA) were randomised between SSZ (2–3 g/day), MTX (7.5–15 mg/week), and the COMBI (same dose range) and evaluated double blindly during 52 weeks. Plasma homocysteine, serum folate concentrations, and vitamin B12 were measured. The influence of the C677T mutation of the enzyme methylenetetrahydrofolatereductase (MTHFR) gene was analysed. <h3>RESULTS</h3> A slight trend towards increased efficacy and an increased occurrence of minor gastrointestinal toxicity was present in the COMBI group, no differences existed clinically between SSZ and MTX. Only a slight and temporary increase in plasma homocysteine was found in the SSZ group, in contrast with the persistent rise in the MTX group and the even greater increase in the COMBI patients. Patients homozygous for the mutation in the MTHFR gene had significantly higher baseline homocysteine, heterozygous MTHFR genotype induced a significantly higher plasma homocysteine at week 52 compared with no mutation. No correlation was found between clinical efficacy variables and homocysteine. Patients with gastrointestinal toxicity had a significantly greater increase in homocysteine. <h3>CONCLUSION</h3> A persistent increase in plasma homocysteine concentrations was observed in patients treated with MTX alone and more pronounced in combination with SSZ, in contrast with SSZ alone. An increase in plasma homocysteine is related to the C677T mutation in MTHFR. A relation in the change in homocysteine concentrations with (gastrointestinal) toxicity was found, no relation with clinical efficacy existed.
The heterogeneity of obstructive sleep apnoea: Congestion leads to longer respiratory cycle lengths in heart failure
Authors: Christina Efken, Thomas Bitter, Britta Körber, Kevin Bullert, Dieter Horstkotte, Olaf Oldenburg
Journal: European Respiratory Journal (2012)

It is controversial if heart failure (HF) can influence obstructive sleep apnoea (OSA) per se. Previous studies documented increased cycle lengths (CL), ventilation lengths (VL), and circulatory delays (CD) of OSA in HF patients. Aim of the present study was to verify these results in a cohort of well-defined HF patients and to investigate possible interactions of HF and OSA.  Methods: 39 patients with OSA (apnoea-hypopnoea index, AHI > 10/h) with (NYHA ≥ II, LV-EF ≤ 40%; n=26, 18 male, 67.2±9.4 years) and without (EF ≥ 50%, NT-proBNP   Results: AHI as well as obstructive apnoea-index (oAI) were comparable in both groups (AHI= 34.3 ± 26.5/h vs. 32.3±18.0, p=n.s.; oAI=8.5 ± 7.8/h vs. 10.0±10.8, p=n.s.). We were able to verify increased CL, VL, time to peak ventilation (TTPV) and circulatory delay (CD) in patients with HF (CL: 37.8±10.6s vs. 46.0±10.0s, p=0.024; VL: 21.3±7.1 vs. 25.4±6.3, p=0.044; TTPV: 8.3±2.5s vs. 10.6±3.0s, p=0.021; CD: 22.6±3.7s vs. 28.5±7.5s, p=0.005). Apnoea length (AL) was higher in HF patients (16.5±3.9s vs. 20.5±4.9s, p=0.013). Positive and robust correlations between parameters of OSA and degree of congestion were found in OSA patients with HF exclusively: CL, VL, and TTPV increased with elevation of PCWP (CL: r=0.53; p=0.006; VL: r=0.55; p=0.004; TTPV: r=0.47; p=0.015).  Respiratory parameters of OSA (CL, VL, TTPV) correlate with the degree of congestion in patients with OSA and HF, but not in non-HF patients with OSA. These results point to a reciprocal relationship of HF and OSA severity.
Therapeutic ultrasound is not clinically beneficial for acute ankle sprains
Authors: Michael Swain, Nicholas Henschke
Journal: British Journal of Sports Medicine (2012)

▶ van den Bekerom MP, van der Windt DA, Ter Riet G, et al. Therapeutic ultrasound for acute ankle sprains. Cochrane Database Syst Rev 2011;6:CD001250.

Ankle sprains are the most common sports injury, and therapeutic ultrasound is often used in the first phase of treatment.1 Rationale for its use is based on physiological effects demonstrated in laboratory research.2 This review is an update of a Cochrane review first published in 1999 and previously updated in 2004. One randomised clinical trial has been published since then and added to the review.3

To determine the effect of ultrasound therapy compared with placebo, no treatment or other interventions in the clinical management of acute ankle sprain.

This methodology followed those recommended by the Cochrane Collaboration. Electronic databases (the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register …
Variability of routine pulmonary function tests.
Authors: J Hruby, J Butler
Journal: Thorax (1975)

Pulmonary function tests sometimes indicate a progressive deterioration and at other times a 'stepwise' worsening which may be followed by improvement. Interpretation depends on the extent of random or diurnal variations in function. Routing pulmonary function tests (VC, FEV1, FRC, and airway resistance (Raw)) were repeatedly measured in normal subjects, patients with stable irreversible airways obstruction, and patients with stable restrictive disease. In all groups there was a significant (P less than 0.001) diurnal variation in Raw, with high values in the morning, low values at noon, and rising values in the evening. The midday Raw values were about 80% of the highest daily values. The considerable random and diurnal variability seen in all tests is reflected in the range of high and low values (% of mean individual response) in individuals. The largest variation in an individual between measurements taken at two different times was 81% in Raw (range: 40% above to 41% below the mean). There was less variation in FEV1 (29%), FRC (62%), and VC (30%). Thus the finding of a stepwise change in function could reflect its natrual variability. When repeated studies are done to assess progress or the effects of therapy on disease, there are many factors, including the time of day at which the tests are performed, which should be standardized as far as possible.
Increased aortic blood pressure contributes to potentiated dobutamine inotropic responses after systemic NO synthase inhibition in sheep
Authors: D Penny
Journal: Cardiovascular Research (1998)

To determine whether inotropic responses to the beta-adrenergic agonist dobutamine are potentiated by systemic inhibition of nitric oxide synthase (NOS) with the L-arginine analogue N omega-nitro-L-arginine (L-NNA), and to establish to what extent any observed responses are related to the increase in aortic blood pressure accompanying systemic NOS inhibition.Dobutamine was infused incrementally at rates of 1, 2.5, 5 and 10 micrograms/kg/min in 15 open-chest, anaesthetised ewes before and after inhibition of NO synthesis with i.v. L-NNA (n = 8), or elevation of mean aortic blood pressure to the same extent as attained with NOS inhibition using proximal arterial occlusion (n = 7).By the peak infusion rate, dobutamine increased the maximal rate of rise of left ventricular pressure (LV dP/dtMAX) by 100% (p < 0.001) and reduced LV stroke work by 18% (p < 0.01). L-NNA and arterial occlusion increased resting mean aortic blood pressure by 55 +/- 4 and 51 +/- 3 mmHg respectively. Compared to dobutamine alone, subsequent peak dobutamine-related increases in LV dP/dtMAX were augmented by 76% after L-NNA and by 88% after arterial occlusion (both p < 0.001). Moreover, dobutamine increased LV stroke work by 23% at infusion rates of 1-5 micrograms/kg/min (p < 0.001) after L-NNA, and by 17% at an infusion rate of 1 microgram/kg/min (p < 0.01) after arterial occlusion.Systemic NOS inhibition potentiates the effects of dobutamine on LV isovolumic and pumping performance in the intact circulation, but this potentiation is in large part related to the increase in arterial blood pressure accompanying NOS inhibition.