tbuckley/cabot-search huggingface dataset:
Mutations in theCOL4A4 and COL4A3 Genes Cause Familial Benign Hematuria
Authors: Ce[Combining Grave Accent]lia Badenas, Manuel Praga, Bárbara Tazón, Laurence Heidet, Christelle Arrondel, Anna Armengol, Amado Andrés, Enrique Morales, Juan Antonio Camacho, Xose Lens, Sonia Dávila, Montse Mila[Combining Grave Accent], Corinne Antignac, Alejandro Darnell, Roser Torra
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Familial benign hematuria (FBH) is a common autosomal dominant disorder characterized by the presence of persistent or recurrent hematuria. The clinical and pathologic features of this syndrome resemble those of early Alport syndrome (AS), and for this reason a common molecular defect has been proposed. The COL4A3/4 genes seem to be involved in both autosomal AS and FBH. This study involves a linkage analysis for the COL4A3/4 loci and a search for mutations within these genes in 11 biopsy-proven FBH families. Haplotype analysis showed that linkage to the COL4A3/4 locus could not be excluded in eight of nine families. One family was not linked to this locus; however, it included three affected women who could be X-linked AS carriers. Two families were too small to perform linkage analysis. COL4A3 and COL4A4 mutation screening disclosed six new pathogenic mutations, two in the COL4A3 gene (G985V and G1015E) and four in the COL4A4 gene (3222insA, IVS23-1G&gt;C, 31del11, and G960R). It is the first time that mutations within the COL4A3 gene are described in families with FBH. This study clearly demonstrates the main role of the COL4A4 and COL4A3 genes in the pathogenesis of FBH.
Docosahexaenoic Acid and Butyrate Synergistically Induce Colonocyte Apoptosis by Enhancing Mitochondrial Ca2+ Accumulation
Authors: Satya Sree N. Kolar, Rola Barhoumi, Joanne R. Lupton, Robert S. Chapkin
Journal: Cancer Research (2007)

Abstract We have previously shown that butyrate, a short-chain fatty acid fiber fermentation product, induces colonocyte apoptosis via a nonmitochondrial, Fas-mediated, extrinsic pathway. Interestingly, fermentable fiber when combined with fish oil containing docosahexaenoic acid (DHA, 22:6n-3) exhibits an enhanced ability to induce apoptosis and protect against colon tumorigenesis. To determine the molecular mechanism of action, the effect of DHA and butyrate cotreatment on intracellular Ca2+ homeostasis was examined. Mouse colonocytes were treated with 50 μmol/L DHA or linoleic acid (LA) for 72 h ± butyrate (0–10 mmol/L) for the final 24 h. Cytosolic and mitochondrial Ca2+ levels were measured using Fluo-4 and Rhod-2. DHA did not alter basal Ca2+ or the intracellular inositol trisphosphate (IP3) pool after 6 h butyrate cotreatment. In contrast, at 12 and 24 h, DHA- and butyrate-treated cultures exhibited a 25% and 38% decrease in cytosolic Ca2+ compared with LA and butyrate. Chelation of extracellular Ca2+ abolished the effect of thapsigargin on the IP3-releasable Ca2+ pool. DHA and butyrate cotreatment compared with untreated cells increased the mitochondrial-to-cytosolic Ca2+ ratio at 6, 12, and 24 h by 73%, 18%, and 37%, respectively. The accumulation of mitochondrial Ca2+ preceded the onset of apoptosis. RU-360, a mitochondrial-uniporter inhibitor, abrogated mitochondrial Ca2+ accumulation and also partially blocked apoptosis in DHA and butyrate cotreated cells. Collectively, these data show that the combination of DHA and butyrate, compared with butyrate alone, further enhances apoptosis by additionally recruiting a Ca2+-mediated intrinsic mitochondrial pathway. [Cancer Res 2007;67(11):5561–8]
Platelets Contribute to the Pathogenesis of Experimental Autoimmune Encephalomyelitis
Authors: Harald F. Langer, Eun Young Choi, Hong Zhou, Rebecca Schleicher, Kyoung-Jin Chung, Zhongshu Tang, Kerstin Göbel, Khalil Bdeir, Antonios Chatzigeorgiou, Connie Wong, Sumeena Bhatia, Michael J. Kruhlak, John W. Rose, James B. Burns, Kenneth E. Hill, Hongchang Qu, Yongqing Zhang, Elin Lehrmann, Kevin G. Becker, Yunmei Wang, Daniel I. Simon, Bernhard Nieswandt, John D. Lambris, Xuri Li, Sven G. Meuth, Paul Kubes, Triantafyllos Chavakis
Journal: Circulation Research (2012)

Rationale: Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function of platelets in inflammatory and autoimmune pathologies is thus far poorly defined. Objective: We addressed the role of platelets in mediating CNS inflammation in EAE. Methods and Results: We found that platelets were present in human MS lesions as well as in the CNS of mice subjected to EAE but not in the CNS from control nondiseased mice. Platelet depletion at the effector-inflammatory phase of EAE in mice resulted in significantly ameliorated disease development and progression. EAE suppression on platelet depletion was associated with reduced recruitment of leukocytes to the inflamed CNS, as assessed by intravital microscopy, and with a blunted inflammatory response. The platelet-specific receptor glycoprotein Ibα (GPIbα) promotes both platelet adhesion and inflammatory actions of platelets and targeting of GPIbα attenuated EAE in mice. Moreover, targeting another platelet adhesion receptor, glycoprotein IIb/IIIa (GPIIb/IIIa), also reduced EAE severity in mice. Conclusions: Platelets contribute to the pathogenesis of EAE by promoting CNS inflammation. Targeting platelets may therefore represent an important new therapeutic approach for MS treatment.
Impairment by damage of the pterygopalatine ganglion of nitroxidergic vasodilator nerve function in canine cerebral and retinal arteries.
Authors: N Toda, K Ayajiki, K Yoshida, H Kimura, T Okamura
Journal: Circulation Research (1993)

Histochemical study revealed that transcutaneous injection of ethanol into the vicinity of the pterygopalatine ganglion greatly decreased the positive staining for NADPH diaphorase activity after 1 week in the ipsilateral ganglion of a dog and abolished the staining of perivascular nerves in the middle and posterior cerebral arteries. Transmural electrical stimulation or nicotine produced a relaxation in middle and posterior cerebral arteries isolated from the side with the nontreated ganglion (control side), whereas the relaxation was abolished or reversed to a contraction in the arteries from the side with the ethanol-treated ganglion. Nitric oxide-induced relaxations did not differ in the arteries from both sides. The response to nerve stimulation of the control arteries was suppressed by treatment with NG-nitro-L-arginine (L-NA), an inhibitor of nitric oxide synthase, and the inhibition was reversed by L-arginine. Nicotine produced a contraction followed by a relaxation in central retinal arterial strips obtained from the control side; the relaxation was abolished and the contraction was potentiated in the arteries from the treated side. The nicotine-induced relaxation was abolished by L-NA, and the contraction was suppressed by phentolamine. On the other hand, the nicotine-induced relaxation in superficial temporal arteries, susceptible to L-NA, was not attenuated by treatment with ethanol. The findings obtained so far support our hypothesis that nitric oxide released from the vasodilator nerve acts as a transmitter to produce arterial smooth muscle relaxation and suggest that the nerve fibers to the cerebral and retinal arteries arise from the pterygopalatine ganglion.
Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease
Authors: Tazeen H. Jafar, Paul C. Stark, Christopher H. Schmid, Marcia Landa, Guiseppe Maschio, Carmelita Marcantoni, Paul E. De Jong, Dick De Zeeuw, Shahnaz Shahinfar, Piero Ruggenenti, Guiseppe Remuzzi, Andrew S. Levey, None for the Aiprd Study Group
Journal: Kidney International (2001)
Heterozygosity for a Surfactant Protein C Gene Mutation Associated with Usual Interstitial Pneumonitis and Cellular Nonspecific Interstitial Pneumonitis in One Kindred
Authors: Alan Q. Thomas, Kirk Lane, John Phillips, Melissa Prince, Cheryl Markin, Marcy Speer, David A. Schwartz, Radhika Gaddipati, Annis Marney, Joyce Johnson, Richard Roberts, Jonathan Haines, Mildred Stahlman, James E. Loyd
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Familial pulmonary fibrosis is a heterogeneous group of interstitial lung diseases of unknown cause that is associated with multiple pathologic subsets. Mutations in the surfactant protein C (SP-C) gene (SFTPC) are associated with familial desquamative and nonspecific interstitial pneumonitis. Genetic studies in familial usual interstitial pneumonitis have been inconclusive. Using a candidate gene approach, we found a heterozygous exon 5 + 128 T→A transversion of SFTPC in a large familial pulmonary fibrosis kindred, including adults with usual interstitial pneumonitis and children with cellular nonspecific interstitial pneumonitis. The mutation is predicted to substitute a glutamine for a conserved leucine residue and may hinder processing of SP-C precursor protein. SP-C precursor protein displayed aberrant subcellular localization by immunostaining. Electron microscopy of affected lung revealed alveolar type II cell atypia, with numerous abnormal lamellar bodies. Mouse lung epithelial cells transfected with the SFTPC mutation were notable for similar electron microscopy findings and for exaggerated cellular toxicity. We show that an SFTPC mutation segregates with the pulmonary fibrosis phenotype in this kindred and may cause type II cellular injury. The presence of two different pathologic diagnoses in affected relatives sharing this mutation indicates that in this kindred, these diseases may represent pleiotropic manifestations of the same central pathogenesis.
Population Attributable Risk for Breast Cancer: Diet, Nutrition, and Physical Exercise
Authors: Mezzetti Maura, Peter Boyle, Carlo La Vecchia, Adriano Decarli, Renato Talamini, Silvia Franceschi
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The percentages of breast cancer cases in a given population attributable to specific risk factors (i.e., the population-attributable risks) can be calculated; determination of such risks associated with potentially modifiable risks factors, such as diet (e.g., levels of consumption of fruits, vegetables, vitamins, etc.), alcohol consumption, exercise, and body weight, are necessary to focus prevention strategies. Methods: With the use of data from a case-control study conducted in Italy from June 1991 through April 1994 on 2569 breast cancer case subjects and 2588 control subjects, we calculated multivariate odds ratios and populationattributable risks for breast cancer in relation to dietary β-carotene and vitamin E intake, alcohol consumption, physical activity, and, for postmenopausal women, body mass index. Results: Among all subjects, the following attributable risks for the indicated risk factors were observed: 10.7% (95% confidence interval [CI] = 4.4%–17.0%) for high alcohol intake (i.e., >20 g/day), 15.0% (95% CI = 7.4%–22.9%) for low β-carotene intake (i.e., <3366 µg/day), 8.6% (95% CI = .0.4%–17.5%) for low vitamin E intake (i.e., <8.5 mg/day), and 11.6% (95% CI = .0.1%–23.3%) for low levels of physical activity. The risks associated with alcohol and β-carotene intake were larger among premenopausal women, and the risk associated with physical activity was larger among postmenopausal women. Being overweight accounted for 10.2% (95% CI = 0.2%–20.2%) of breast cancer cases in postmenopausal women. β-Carotene plus alcohol accounted for 28.1% (95% CI = 16.8–39.4) of the cases. β-Carotene and physical activity accounted for 32% (95% CI = 14.3–49.8), and these three factors together accounted for 33% (95% CI = 19.9–46.1) of the breast cancer cases in the overall dataset. Conclusion: Exposure to a few selected and potentially modifiable risk indicators explained about one third of the cases of breast cancer in this Italian population, indicating the theoretical scope for prevention of the disease.
Essence of Evidence-Based Medicine: A Case Report
Authors: George P. Browman
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To illustrate the complexities of the evidence-based approach in clinical oncology practice and the implications for guidelines and evaluation of processes of care. PATIENT AND METHODS: A case report is presented in which a limited systematic review of the literature was used to address a specific clinical problem in an individual patient. Experts' opinions were also sought. RESULTS: A reasonable clinical decision was made by a participating patient based on indirect evidence of benefit that would be insufficient to support the same decision as a health policy in some jurisdictions. CONCLUSION: The practice of evidence-based oncology requires clinical judgment about the validity and applicability of research evidence. The factors that influence an evidence-based decision in the clinical context differ from those in the broader policy context, which could lead to legitimate differences in recommendations based on the same information. Used properly, the individual case report can be a powerful tool to illustrate complex clinical decision phenomena.
Niacin attenuates acute lung injury induced by lipopolysaccharide in the hamster
Authors: A Nagai, S Yasui, Y Ozawa, H Uno, K Konno
Journal: European Respiratory Journal (1994)

Lipopolysaccharide plays a major role in the development of lung injury induced by Gram-negative bacteria, but a protective agent to attenuate the LPS-induced lung injury has not been found. The aim of this study was to examine the effects of niacin on LPS-induced acute lung injury. We administered LPS (Escherichia coli) 0.01 mg.100 g-1 body weight, transtracheally into the lungs of hamsters. Niacin (250 or 500 mg.kg-1 body weight) was injected intraperitoneally 24 h before, and 1 h after the LPS administration. LPS treatment increased wet/dry lung weight, albumin content and neutrophil counts in bronchoalveolar lavage fluid. In hamsters treated with niacin, wet/dry lung weight, albumin content and intra-alveolar cell counts were normal. Nicotinamide adenine dinucleotide (NAD) was significantly decreased in lung tissue of hamsters treated with LPS alone, but was increased in hamsters treated with LPS and niacin. Histopathological examination revealed that niacin-treated LPS-administered hamsters had lungs with no or occasional inflammatory cell infiltration in alveolar spaces, in contrast to the lungs of LPS-treated hamsters, which were infiltrated with numerous inflammatory cells. We conclude that niacin attenuates LPS-induced acute lung injury, probably, in part, by preventing the depletion of NAD.
Distinguishing Between the Validity and Utility of Psychiatric Diagnoses
Authors: Robert Kendell, Assen Jablensky
Journal: American Journal of Psychiatry (2002)

The meaning of the terms "validity" and "utility" as they apply to psychiatric diagnoses is examined.The authors discuss the concepts of validity, utility, and disease; review assumptions that have been made about mental disorders as disease entities; and examine the evidence that mental disorders are separated from one another and from normality by natural boundaries (zones of rarity).Despite historical and recent assumptions to the contrary, there is little evidence that most currently recognized mental disorders are separated by natural boundaries. Researchers are increasingly assuming that variation in symptoms is continuous and are therefore questioning the validity of contemporary classifications.It is important to distinguish between validity and utility in considering psychiatric diagnoses. Diagnostic categories defined by their syndromes should be regarded as valid only if they have been shown to be discrete entities with natural boundaries that separate them from other disorders. Although most diagnostic concepts have not been shown to be valid in this sense, many possess high utility by virtue of the information about outcome, treatment response, and etiology that they convey. They are therefore invaluable working concepts for clinicians.
Acquired cutaneous lymphangiectasia
Authors: SANG EUN MOON, JAI IL YOUN, YOO SHIN LEE
Journal: British Journal of Dermatology (1993)

We report a case of acquired cutaneous lymphangiectasia associated with underlying malignancy, and following an arthrotomy. Clinical and histological features were identical with those of acquired lymphangioma. Lymphangiography showed signs of acquired lymphatic obstruction. Both the underlying tumour and the arthrotomy were thought to be contributory factors.
YB-1 Regulation of the Human and Rat Gelatinase A Genes via Similar Enhancer Elements
Authors: PETER R. MERTENS, MARIA ALEXANDRA ALFONSO-JAUME, KARIN STEINMANN, DAVID H. LOVETT
Journal: Journal of the American Society of Nephrology (1999)

Experimental and clinical studies strongly suggest that gelatinase A plays a central role in the evolution of glomerular injury and sclerosis. The sequences of the 5' flanking regions of the human and rat gelatinase A genes do not share similarities with other members of the matrix metalloproteinase gene family and are regulated in a distinctive manner. The human and rat gelatinase A genes include regions of significant homology (r2 human; RE-1 rat), which have been shown to act as potent cis-activators of transcription. The rat RE-1 sequence interacts specifically with the developmentally regulated transcription factors AP2 and YB-1, resulting in a synergistic activation of gelatinase A transcription. Although the human r2 sequence specifically interacts with AP2 (Mol Cell Biol 10: 6524-6532, 1990), there is no clear evidence for the presence of a canonical YB-1 binding site (Y-box) within this sequence. This study demonstrates, despite the absence of a canonical Y-box sequence in the r2 element, that YB-1 and AP2 specifically interact with r2, yielding synergistic transactivation of the human gelatinase A gene. It is concluded that the r2 element is the conserved functional analog of the RE-1 element, and that interactions of AP2 and YB-1 govern human gelatinase A gene expression.
Quality of Care Is Associated with Survival in Vulnerable Older Patients
Authors: Takahiro Higashi, Paul G. Shekelle, John L. Adams, Caren J. Kamberg, Carol P. Roth, David H. Solomon, David B. Reuben, Lillian Chiang, Catherine H. MacLean, John T. Chang, Roy T. Young, Debra M. Saliba, Neil S. Wenger
Journal: Annals of Internal Medicine (2005)

Although assessment of the quality of medical care often relies on measures of process of care, the linkage between performance of these process measures during usual clinical care and subsequent patient outcomes is unclear.To examine the link between the quality of care that patients received and their survival.Observational cohort study.Two managed care organizations.Community-dwelling high-risk patients 65 years of age or older who were continuously enrolled in the managed care organizations from 1 July 1998 to 31 July 1999.Quality of care received by patients (as measured by a set of quality indicators covering 22 clinical conditions) and their survival over the following 3 years.The 372 vulnerable older patients were eligible for a mean of 21 quality indicators (range, 8 to 54) and received, on average, 53% of the care processes prescribed in quality indicators (range, 27% to 88%). Eighty-six (23%) persons died during the 3-year follow-up. There was a graded positive relationship between quality score and 3-year survival. After adjustment for sex, health status, and health service use, quality score was not associated with mortality for the first 500 days, but a higher quality score was associated with lower mortality after 500 days (hazard ratio, 0.64 [95% CI, 0.49 to 0.84] for a 10% higher quality score).The observational design limits causal inference regarding the effect of quality of care on survival.Better performance on process quality measures is strongly associated with better survival among community-dwelling vulnerable older adults.
Management of Patients With Acute Coronary Syndromes in the United States by Platelet Glycoprotein IIb/IIIa Inhibition
Authors: A. Michael Lincoff, Robert A. Harrington, Robert M. Califf, Judith S. Hochman, Alan D. Guerci, E. Magnus Ohman, Carl J. Pepine, Steven L. Kopecky, Neal S. Kleiman, Cynthia M. Pacchiana, Lisa G. Berdan, Michael M. Kitt, Maarten L. Simoons, Eric J. Topol
Journal: Circulation (2000)

Background —A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation. Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed. The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States. Methods and Results —Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase–MB elevation were eligible for enrollment. Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States. Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours. Other medical therapies and revascularization strategies were at the discretion of the treating physician. Eptifibatide reduced the rate of the primary end point of death or myocardial infarction by 30 days from 15.4% to 11.9% ( P =0.003) among patients in the United States. The treatment effect was achieved early and maintained over a period of 6 months (18.9% versus 15.2%; P =0.004). Bleeding events were more common in patients receiving eptifibatide but were predominantly associated with invasive procedures. The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world. Conclusions —Platelet glycoprotein IIb/IIIa receptor blockade with eptifibatide reduces the incidence of death or myocardial infarction among patients treated for acute ischemic syndromes without ST-segment elevation within the United States.
Advances in Quantitative Electroencephalogram Analysis Methods
Authors: Nitish V. Thakor, Shanbao Tong
Journal: Annual Review of Biomedical Engineering (2004)

Quantitative electroencephalogram (qEEG) plays a significant role in EEG-based clinical diagnosis and studies of brain function. In past decades, various qEEG methods have been extensively studied. This article provides a detailed review of the advances in this field. qEEG methods are generally classified into linear and nonlinear approaches. The traditional qEEG approach is based on spectrum analysis, which hypothesizes that the EEG is a stationary process. EEG signals are nonstationary and nonlinear, especially in some pathological conditions. Various time-frequency representations and time-dependent measures have been proposed to address those transient and irregular events in EEG. With regard to the nonlinearity of EEG, higher order statistics and chaotic measures have been put forward. In characterizing the interactions across the cerebral cortex, an information theory-based measure such as mutual information is applied. To improve the spatial resolution, qEEG analysis has also been combined with medical imaging technology (e.g., CT, MR, and PET). With these advances, qEEG plays a very important role in basic research and clinical studies of brain injury, neurological disorders, epilepsy, sleep studies and consciousness, and brain function.