tbuckley/cabot-search huggingface dataset:
Neutrophil gelatinase-associated lipocalin in idiopathic pulmonary fibrosis
Authors: Kohei Ikezoe, Tomohiro Handa, Kiyoshi Mori, Kizuku Watanabe, Kiminobu Tanizawa, Kensaku Aihara, Tatsuaki Tsuruyama, Aya Miyagawa-Hayashino, Akihiko Sokai, Takeshi Kubo, Shigeo Muro, Sonoko Nagai, Toyohiro Hirai, Kazuo Chin, Michiaki Mishima
Journal: European Respiratory Journal (2014)

To the Editor: 

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kD lipocalin that is covalently bound to matrix metalloproteinase (MMP)-9 produced by neutrophils [1]. NGAL in blood or bronchoalveolar lavage fluid (BALF) may reflect neutrophilic inflammation in the lungs [2, 3], and it is highly induced in injured epithelial cells, including those in the lung [4]. Possible roles for neutrophilic inflammation and epithelial injury have been reported in idiopathic pulmonary fibrosis (IPF). Thus, we hypothesised that NGAL may be associated with the pathogenesis of IPF. To investigate the roles of NGAL in IPF, we used immunohistochemical staining for lung specimens and measured plasma and BALF NGAL levels. Our study was approved by the Ethics Committee of Kyoto University (approval No. E438), and written informed consent was obtained from all study participants.

First, we immunohistochemically stained the lung tissue specimens of six IPF patients, two nonspecific interstitial pneumonia (NSIP) patients, and a control (normal area distant from the lesion of surgically diagnosed organising pneumonia) for NGAL using a conventional method [5]. We also performed sequential immunofluorescent staining for NGAL and MMP-9. Immunohistochemical staining showed that NGAL was abundantly expressed in airway epithelial cells that covered the honeycomb cysts in IPF (fig. 1a and b). Further, histologically normal bronchioles in the fibrotic lesions also exhibited abundant NGAL expression, although apparently normal alveolar walls exhibited little NGAL expression. NGAL was also expressed in macrophages, neutrophils and some alveolar epithelial cells.



Figure 1– 
Immunohistochemical staining results for neutrophil gelatinase-associated lipocalin (NGAL) in lung specimens from: a and b) idiopathic pulmonary fibrosis (IPF) …
Preservation of intercalated cell H(+)-ATPase in two patients with lupus nephritis and hyperkalemic distal renal tubular acidosis.
Authors: B Bastani, D Underhill, N Chu, R D Nelson, L Haragsim, S Gluck
Journal: Journal of the American Society of Nephrology (1997)

In patients with Sjögren's syndrome and a secretory-defect distal renal tubular acidosis (dRTA), absence of vacuolar H(+)-ATPase from collecting duct intercalated cells has been reported. The H(+)-ATPase was examined in two patients with lupus nephritis and hyperkalemic (presumed voltage defect) dRTA. Both patients had a positive urine anion gap, alkaline urine despite acidemia, no rise in urine PCO2 with alkaluria, a urine pH > 5.5, and urine potassium excretion rate not significantly increased after 80 mg of intravenous furosemide. In both patients, immunocytochemistry of renal biopsy frozen sections with an anti-H(+)-ATPase monoclonal antibody showed bright staining of the proximal tubule brush border and collecting duct intercalated cells. In one patient, routine immunofluorescence analysis of a frozen section of her kidney biopsy with antihuman IgG showed staining of the collecting duct, indicative of autoantibodies to this segment. Moreover, rat kidney sections incubated with her serum showed labeling of the intercalated cells. On immunoblots of human kidney microsomal membranes performed with serum from both patients, an immunoreactive polypeptide was observed at M(r) approximately 56 kD that was not seen with control serum. Neither patient's sera reacted with affinity-purified bovine H(+)-ATPase or with lysates from 293 cell fibroblasts in which either of both isoforms of the human H(+)-ATPase B subunit (56 kD) were expressed. These findings demonstrate that the spectrum of dRTA includes the preservation of H(+)-ATPase in intercalated cells, in patients with presumed voltage defect dRTA. Moreover, some patients may have autoantibodies to the intercalated cells that are not directed to subunits of the H(+)-ATPase.
Questioning the challenging role of epithelial-to-mesenchymal transition in liver injury
Authors: David Scholten, Ralf Weiskirchen
Journal: Hepatology (2011)

Cirrhosis is the end result of chronic liver disease. Hepatic stellate cells (HSC) are believed to be the major source of collagen-producing myofibroblasts in cirrhotic livers. Portal fibroblasts, bone marrow-derived cells, and the epithelial-to-mesenchymal transition (EMT) might also contribute to the myofibroblast population in damaged livers. Fibroblast-specific protein 1 (FSP1, also called S100A4) is considered a marker of fibroblasts in different organs undergoing tissue remodeling and is used to identify fibroblasts derived from EMT in several organs, including the liver. The aim of this study was to characterize FSP1-positive cells in human and experimental liver disease. FSP1-positive cells were increased in human and mouse experimental liver injury including liver cancer. However, FSP1 was not expressed by HSC or type I collagen-producing fibroblasts. Likewise, FSP1-positive cells did not express classical myofibroblast markers, including alpha smooth muscle actin (α-SMA) and desmin, and were not myofibroblast precursors in injured livers as evaluated by genetic lineage tracing experiments. Surprisingly, FSP1-positive cells expressed F4/80 and other markers of the myeloid-monocytic lineage as evaluated by double immunofluorescence staining, cell fate tracking, flow cytometry, and transcriptional profiling. Similar results were obtained for bone marrow-derived and peritoneal macrophages. FSP1-positive cells were characterized by increased expression of COX2, osteopontin, inflammatory cytokines, and chemokines but reduced expression of MMP3 and TIMP3 compared with Kupffer cells/macrophages. These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer.
Regulation of GABA<sub>A</sub>Receptor Subunit Expression by Pharmacological Agents
Authors: Mikko Uusi-Oukari, Esa R. Korpi
Journal: Pharmacological Reviews (2010)

The γ-aminobutyric acid (GABA) type A receptor system, the main fast-acting inhibitory neurotransmitter system in the brain, is the pharmacological target for many drugs used clinically to treat, for example, anxiety disorders and epilepsy, and to induce and maintain sedation, sleep, and anesthesia. These drugs facilitate the function of pentameric GABA<sub>A</sub> receptors that exhibit widespread expression in all brain regions and large structural and pharmacological heterogeneity as a result of composition from a repertoire of 19 subunit variants. One of the main problems in clinical use of GABA<sub>A</sub> receptor agonists is the development of tolerance. Most drugs, in long-term use and during withdrawal, have been associated with important modulations of the receptor subunit expression in brain-region-specific manner, participating in the mechanisms of tolerance and dependence. In most cases, the molecular mechanisms of regulation of subunit expression are poorly known, partly as a result of neurobiological adaptation to altered neuronal function. More knowledge has been obtained on the mechanisms of GABA<sub>A</sub> receptor trafficking and cell surface expression and the processes that may contribute to tolerance, although their possible pharmacological regulation is not known. Drug development for neuropsychiatric disorders, including epilepsy, alcoholism, schizophrenia, and anxiety, has been ongoing for several years. One key step to extend drug development related to GABA<sub>A</sub> receptors is likely to require deeper understanding of the adaptational mechanisms of neurons, receptors themselves with interacting proteins, and finally receptor subunits during drug action and in neuropsychiatric disease processes.
Safety of sputum induction in chronic obstructive pulmonary disease
Authors: P.H. Rytilä, A.E. Lindqvist, L.a Laitinen
Journal: European Respiratory Journal (2000)

The aim of the present study was to evaluate the safety of sputum induction in patients with varying severity of chronic obstructive pulmonary disease. The subjects were 28 smokers with baseline forced expiratory volume in one second (FEV1) of (mean and range) 1.8 (0.8-2.9) L that is 53 (28-69)% of the predicted and reversibility of 2.5 (-7.4-9.9)%. Sputum was induced after premedication with 200 microg salbutamol at increasing concentrations (0.9, 3, 4, and 5%) of hypertonic saline nebulized by an ultrasonic nebulizer. The procedure was well tolerated, and none of the patients reported major side-effects. However, the mean change from prebronchodilator FEV1 during induction was -8.5 (-23-11)%, p=0.001, and from postbronchodilator FEV1 -10.7 (-25-5)%, p&lt;0.0001. Three (11%) of the patients had a fall in FEV1 from the prebronchodilator baseline of &gt;20%, and a further 10 (36%) had a fall of 10-20%. Patients with greater reversibility in airway obstruction seemed to get the best benefit from the bronchodilator pretreatment, since there was an inverse relationship between reversibility in FEV1 and fall in FEV1 during induction (r=-0.4, p=0.03). It is concluded that sputum induction by hypertonic saline inhalation can cause meaningful bronchoconstriction in patients with chronic obstructive pulmonary disease, despite pretreatment with an inhaled beta2-agonist. The results highlight the importance of monitoring spirometry during sputum induction to detect bronchoconstriction.
Implantable Left Ventricular Assist Devices Provide an Excellent Outpatient Bridge to Transplantation and Recovery
Authors: Joseph J DeRose, Juan P Umana, Michael Argenziano, Katharine A Catanese, Michael T Gardocki, Margaret Flannery, Howard R Levin, Benjamin C Sun, Eric A Rose, Mehmet C Oz
Journal: Journal of the American College of Cardiology (1997)

Objectives. Our recent experience with outpatient left ventricular assist device (LVAD) support is presented to demonstrate the possibilities and limitations of long-term outpatient mechanical circulatory assistance. Background. The experience with inpatient LVAD support as a bridge to transplantation has proved the efficacy of such therapy in improving circulatory hemodynamic status, restoring normal end-organ function and facilitating patient rehabilitation. With miniaturization of the power supplies and controllers, such mechanical circulatory support can now be accomplished in an outpatient setting. Methods. Between March 1993 and February 1997, 32 patients (26 male, 6 female, mean [±SEM] age 49 ± 15 years) underwent implantation of the ThermoCardiosystems (TCI) Heartmate vented electric (VE) LVAD. The VE LVAD is powered by batteries worn on shoulder holsters and is operated by a belt-mounted system controller, allowing unrestricted patient ambulation and hospital discharge. Results. Mean duration of support was 122 ± 26 days (range 3 to 605), with a survival rate to transplantation or explantation of 78%. Nineteen patients were discharged from the hospital on mean postoperative day 41 ± 4 (range 17 to 68), for an outpatient support time of 108 ± 30 days (range 2 to 466). Four patients underwent early transplantation and could not participate in the discharge program, and three patients currently await discharge. The complication rate was not statistically different from that encountered in our previous 52 patients with a pneumatic LVAD. Conclusions. Outpatient LVAD support is safe and provides improved quality of life for patients awaiting transplantation. Wearable and totally implantable LVADs should be studied as permanent treatment options for patients who are not candidates for heart transplantation.
Immediate effect on fertility of a gluten-free diet in women with untreated coeliac disease
Authors: R. Nenna, M. Mennini, L. Petrarca, M. Bonamico
Journal: Gut (2010)

In a recent paper in Gut , describing a Swedish population-based cohort, Zugna et al found that women with coeliac disease had normal fertility, but their fertility had decreased in the 2 years preceding the diagnosis of coeliac disease.1

This study provides important answers to fertility problems in patients with coeliac disease by analysing a nationwide database. The results, however, must be interpreted with caution. This paper may be considered confusing because the role of coeliac disease as one of the causes of infertility has been underestimated taking into account population studies in general. Infertility, spontaneous abortion and delayed puberty represent subclinical coeliac disease presentations …
Racial/ethnic differences in breast cancer survival among San Francisco Bay Area women
Authors: J. L. Hsu, S. L. Glaser, D. W. West
Journal: JNCI Journal of the National Cancer Institute (1997)

Considerable attention has been directed to the observation that the ageadjusted incidence of female breast cancer in the San Francisco Bay Area (114 per 100 000 persons) 1 is higher than the national incidence (109 per 100 000 persons) 2 and is approximately 50% higher than in most European countries (1).Although breast cancer is the most common cancer among women in the San Francisco Bay Area, its incidence varies substantially by racial/ethnic group (average annual age-adjusted rates per 100 000 persons, 1988-1993, of 128 for whites, 102 for blacks, 86 for Japanese, 83 for Hispanics, 76 for Filipinos, and 69 for Chinese).The high incidence and racial/ethnic variation in breast cancer rates in our region prompted us to examine corresponding patterns in survival, particularly inasmuch as breast cancer survival among women in many racial/ethnic groups (i.e., non-white and non-black) remains relatively understudied (2-4).The purpose of this analysis was to characterize breast cancer survival among the six largest racial/ethnic groups in the San Francisco Bay Area and to examine stage at diagnosis as an explanatory factor for observed differences.We evaluated data on 11 431 white, 1326 black, 903 Hispanic, 500 Chinese, 397 Filipino, and 161 Japanese women in the San Francisco Bay Area who were diagnosed with primary, invasive breast cancers during the period from January
Effect of α-Difluoromethylornithine on Rectal Mucosal Levels of Polyamines in a Randomized, Double-Blinded Trial for Colon Cancer Prevention
Authors: Frank L. Meyskens, Eugene W. Gerner, Scott Emerson, Daniel Pelot, Theodore Durbin, Karen Doyle, Westley Lagerberg
Journal: JNCI Journal of the National Cancer Institute (1998)

Polyamines (e.g., putrescine, spermidine, and spermine) are required for optimal cell growth. Inhibition of polyamine synthesis suppresses carcinogen-induced epithelial cancers, including colon cancer, in animal models. In a short-term phase IIa trial, we determined that low doses of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (an enzyme involved in polyamine synthesis), reduced the polyamine content of normal-appearing rectal mucosa of subjects with a prior history of resected colon polyps. In a follow-up study, we have attempted to determine the lowest dose of DFMO that can suppress the polyamine content of rectal mucosa over a course of 1 year with no or minimal side effects.Participants were randomly assigned to daily oral treatment with a placebo or one of three doses (0.075, 0.20, or 0.40 g/m2) of DFMO. Baseline and serial determinations of polyamine levels in rectal mucosa and extensive symptom monitoring (including audiometric measurements, since DFMO causes some reversible hearing loss at higher doses) were performed over a 15-month period.DFMO treatment reduced putrescine levels in a dose-dependent manner. Following 6 months of treatment, doses of 0.20 and 0.40 g/m2 per day reduced putrescine levels to approximately 34% and 10%, respectively, of those observed in the placebo group. Smaller decreases were seen in spermidine levels and spermidine:spermine ratios. Polyamine levels increased toward baseline values after discontinuation of DFMO. Although there were no statistically significant differences among the dose groups with respect to clinically important shifts in audiometric thresholds and nonaudiologic side effects, statistically significant higher dropout and discontinuation rates were observed in the highest dose group.Polyamine levels in rectal mucosa can be continuously suppressed by daily oral doses of DFMO that produce few or no side effects. A dose of 0.20 g/m2 can be used safely in combination phase IIb or single-agent phase III chemoprevention trials.
Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial
Authors: Robert K Koenekoop, Ruifang Sui, Juliana Sallum, L Ingeborgh van den Born, Radwan Ajlan, Ayesha Khan, Anneke I den Hollander, Frans P M Cremers, Janine D Mendola, Ava K Bittner, Gislin Dagnelie, Ronald A Schuchard, David A Saperstein
Journal: The Lancet (2014)
Deaths caused by restraint vests
Authors: V. J. Di Maio
Journal: JAMA (1986)

To the Editor.—  Patient restraint vests are widely used to prevent individuals from climbing out of or falling from beds and chairs. These devices are used principally for persons manifesting senility or dementia and they are extensively used in nursing homes. During the past two years, the Bexar County (Tex) Medical Examiner's Office has encountered four deaths caused by these vests in nursing homes in our community.  Report of Cases.—  Three cases involved patients strapped in bed with vest restraints, subsequently found hanging over the bed rails from the vests. One person was a 42-year-old woman with Huntington's chorea. The other two, a 91-year-old woman and a 92-year-old man, were diagnosed as being senile. These latter two patients had successfully escaped from restraint vests in the past. The fourth person, a 76-year-old woman, had been tied in a chair with a vest restraint. She had previously escaped by slipping down
Airway Hyperresponsiveness to Methacholine in Mutant Mice Deficient in Endothelin-1
Authors: TAKAHIDE NAGASE, HIROKI KURIHARA, YUKIKO KURIHARA, TOMOKO AOKI, YOSHINOSUKE FUKUCHI, YOSHIO YAZAKI, YASUYOSHI OUCHI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Endothelin-1 (ET-1) has recently been reported to have a potential pathophysiologic role in bronchial asthma. In the current study, we hypothesized whether ET-1 and a gene encoding ET-1 might be involved in airway hyperresponsiveness (AHR), which is a major feature of bronchial asthma. To test this hypothesis, we investigated airway responsiveness in ET-1+ / − heterozygous knockout mice, which genetically produce lower levels of ET-1, and in ET-1+ / + wild-type mice. Airway responsiveness was assessed through the concentration of an agonist required to double lung resistance (EC200 Rl). Unexpectedly, airway responsiveness to methacholine was markedly enhanced in ET-1+ / − heterozygous mice as compared with ET-1+ / + wild-type mice (EC200 Rl: 1.8 ± 0.1 versus 21.6 ± 5.6 mg/ml, p < 0.002). Pretreatment with the nitric oxide (NO) synthase inhibitor Ng-monomethyl-l-arginine (l-NMMA) significantly enhanced methacholine responsiveness in ET-1+ / + wild-type mice, but not in ET-1+ / − heterozygous mice. Meanwhile, there was no difference between ET-1+ / − heterozygous mice and the wild-type mice in airway responsiveness to 5-hydroxytryptamine (5-HT). In sensitized mice, no significant differences in responsiveness to antigen were observed between the two groups. These findings suggest that the gene encoding ET-1 may be potentially involved in the etiology of airway hyperreactivity, and that the decrease in ET-1 concentration is associated with AHR to methacholine. In mice, ET-1 as well as NO may have a significant role in the homeostasis of airway physiology.
Do Hypertension and Diuretic Treatment in Pregnancy Increase the Risk of Schizophrenia in Offspring?
Authors: Holger J. Sørensen, Erik L. Mortensen, June M. Reinisch, Sarnoff A. Mednick
Journal: American Journal of Psychiatry (2003)

Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal neurodevelopment and increase the risk of schizophrenia in offspring.Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug treatment during pregnancy.In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment in the third trimester (odds ratio=2.55 [95% CI=1.21-5.37]), and maternal schizophrenia (odds ratio=11.12 [95% CI=4.60-29.91]). Prenatal exposure to both hypertension and diuretic treatment in the third trimester conferred a 4.01-fold (95% CI=1.41-11.40) elevated risk.Children of mothers with hypertension in pregnancy plus diuretic treatment in the third trimester were at significantly increased risk of developing schizophrenia. In pregnancies complicated by hypertension, diuretics may interfere with aspects of fetal neurodevelopment and thus increase the vulnerability of offspring to the development of schizophrenia later in life.
Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice
Authors: P.H. Youl, M. Janda, J.F. Aitken, C.B. Del Mar, D.C. Whiteman, P.D. Baade
Journal: British Journal of Dermatology (2011)

Journal Article Body‐site distribution of skin cancer, pre‐malignant and common benign pigmented lesions excised in general practice Get access P.H. Youl, P.H. Youl Viertel Centre for Research in Cancer Control, Cancer Council Queensland, PO Box 201, Spring Hill, Qld, Australia 4004School of Population Health, University of Queensland, Qld, Australia Philippa Youl. E‐mail: pipyoul@cancerqld.org.au Search for other works by this author on: Oxford Academic Google Scholar M. Janda, M. Janda School of Public Health, Queensland University of Technology, Qld, Australia Search for other works by this author on: Oxford Academic Google Scholar J.F. Aitken, J.F. Aitken Viertel Centre for Research in Cancer Control, Cancer Council Queensland, PO Box 201, Spring Hill, Qld, Australia 4004School of Population Health, University of Queensland, Qld, Australia Search for other works by this author on: Oxford Academic Google Scholar C.B. Del Mar, C.B. Del Mar School of Medicine, Bond University, Qld, Australia Search for other works by this author on: Oxford Academic Google Scholar D.C. Whiteman, D.C. Whiteman Queensland Institute of Medical Research, Qld, Australia Search for other works by this author on: Oxford Academic Google Scholar P.D. Baade P.D. Baade Viertel Centre for Research in Cancer Control, Cancer Council Queensland, PO Box 201, Spring Hill, Qld, Australia 4004School of Public Health, Queensland University of Technology, Qld, Australia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 1, 1 July 2011, Pages 35–43, https://doi.org/10.1111/j.1365-2133.2011.10337.x Published: 01 July 2011