tbuckley/cabot-search huggingface dataset:
The Sympathetic Nervous System Alterations in Human Hypertension
Authors: Guido Grassi, Allyn Mark, Murray Esler
Journal: Circulation Research (2015)

Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.
New Parents and Mental Disorders
Authors: Trine Munk-Olsen, Thomas Munk Laursen, Carsten Bøcker Pedersen, Ole Mors, Preben Bo Mortensen
Journal: JAMA (2006)

ContextStudies on postpartum mental disorders among mothers have primarily focused on either depression or psychoses and have generally not included the broader spectrum of mental disorders. A few studies have found that some men have symptoms of depression after becoming fathers, but these studies have not documented whether this exceeds the morbidity among men in general.ObjectivesTo estimate the risk of postpartum mental disorders necessitating hospital admission or outpatient contact for mothers as well as fathers during a 1-year postnatal follow-up period after birth of first live-born child and to investigate whether parents in general differ from nonparents in the risk of admission with a mental disorder and how this difference varies with age.Design, Setting, and PatientsRegister-based cohort formed by linking information from Danish health and civil service registers. A total of 2 357 942 Danish-born persons were followed up from their 15th birthday or January 1, 1973, whichever came later, until date of onset of the disorder in question, date of death, date of emigration from Denmark, or July 1, 2005, whichever came first. From 1973 to 2005, a total of 630 373 women and 547 431 men became parents for the first time, and during the first year after childbirth, these parents contributed 1 115 639 person-years at risk.Main Outcome MeasureFirst-time psychiatric hospital admission or outpatient contact 0 to 12 months after becoming a parent.ResultsA total of 1171 mothers and 658 fathers were admitted with a mental disorder to a psychiatric hospital during the first 12 months after parenthood, and the corresponding prevalence of severe mental disorders through the first 3 months after childbirth was 1.03 per 1000 births for mothers and 0.37 per 1000 births for fathers. Compared with women who had given birth 11 to 12 months prior, primiparous women had an increased risk of incident hospital admission with any mental disorder through the first 3 months after childbirth, with the highest risk 10 to 19 days postpartum (relative risk [RR], 7.31; 95% confidence interval [CI], 5.44-9.81). Among mothers, risk was also increased for psychiatric outpatient contacts through the first 3 months after childbirth, also with the highest risk occurring 10 to 19 days postpartum (RR, 2.67; 95% CI, 1.99-3.59). Unlike motherhood, fatherhood was not associated with any increased risk of hospital admission or outpatient contact.ConclusionIn Denmark, the risk of postpartum mental disorders among primiparous mothers is increased for several months after childbirth, but among fathers there is no excess of severe mental disorders necessitating admission or outpatient contacts.
Deep mRNA Sequencing for In Vivo Functional Analysis of Cardiac Transcriptional Regulators
Authors: Scot J. Matkovich, Yan Zhang, Derek J. Van Booven, Gerald W. Dorn
Journal: Circulation Research (2010)

Transcriptional profiling can detect subclinical heart disease and provide insight into disease etiology and functional status. Current microarray-based methods are expensive and subject to artifact.
Evaluating flutter device and the active cycle of breathing technique in non-cystic bronchiectasis: The prospective randomised study
Authors: Gundeniz Altiay, Bilge Uzmezoglu, Necdet Sut, Hakan Tuna, Osman Nuri Hatipoglu
Journal: European Respiratory Journal (2012)

Background: Chest physiotherapy is an important part of the routine treatment of patients with bronchiectasis. The aim of present study was investigate the efficacy of two frequently used physiotherapies in bronchiectasis: active cycle of breathing (ACTB) techniques and the Flutter device.  Methods: A prospective randomized study was performed in 36 stable patients with non-cystic bronchiectasis at home, in which 4 weeks of daily ACTB (n=17) were compared with the Flutter device (n=19). We compared symptoms, pulmonary function tests, dyspnea scores and Health-Related Quality of Life with two different physiotherapy techniques.  Results: We determined cough and weakness was reduced (respectively p=0,000, p=0,004), sputum expectoration was increased (p=0,002), dyspnea score was reduced (for Medical Research Council p=0,001, for Borg Dyspnea Scale p=0,002) and Short Form-36 (SF-36) 9Physical Health9 component summaries score was improved partly (p=0,001) with physiotherapy. No significant changes were note FVC, FEV1 or symptoms between the two techniques. We found only significantly general health (p=0.048) and pain feeling (p=0.011) scores in SF-36 with the Flutter.  Conclusions: Chest physiotherapy is a effective method increasing sputum expectoration, reducing symptoms and dyspnea score and party improvement Health-Related Quality of Life. ACTB and Flutter techniques are suitable usage at home-based treatment.
miR-22 Promotes HBV-Related Hepatocellular Carcinoma Development in Males
Authors: Runqiu Jiang, Lei Deng, Liang Zhao, Xiangcheng Li, Feng Zhang, Yongxiang Xia, Yun Gao, Xuehao Wang, Beicheng Sun
Journal: Clinical Cancer Research (2011)

Previous reports have shown that IL-1α-MyD88-IL-6 signaling is essential in promoting hepatocellular carcinoma (HCC) development in a diethylnitrosamine (DEN)-induced mouse model. We aimed to determine whether interleukin (IL)-1α regulates HCC development in humans.HBV-associated HCC tissue, corresponding adjacent tissue, and normal tissue samples were obtained from 80 male and 36 female patients. IL-1α, ERα, IL-6, and MyD88 were quantified by using real-time PCR and Western blot. Stem-loop PCR was used to quantify miR-22 expression. Luciferase reporter assays were used to study transcriptional regulation.IL-1α was highly expressed in male tumor adjacent tissue compared with normal tissue (P = 0.025); however, this was not the case for female subjects. A linear relationship was observed between increased IL-1α and decreased ERα expression in male tumor adjacent tissue (r = -0.616, P = 0.004). Our results also indicated that estrogen (E2) was suppressed upon IL-1α secretion in ERα-overexpressed HCC cells. We detected high expression of miR-22 in male tumor adjacent tissue compared with controls (P = 0.027); furthermore, we showed that miR-22 downregulates ERα transcription by targeting the 3'-untranslated region. In the DEN-induced model, IL-1α was highly expressed in sprouting tumors and gradually decreased in conjunction with HCC development.Overexpression of miR-22 in male tumor adjacent tissue was associated with downregulated ERα expression, potentially by attenuating the protective effect of estrogen and causing increased IL-1α expression. These results may explain the high incidence of HBV-associated HCC in the male population.
A Classificatory Principle in Schizophrenia
Authors: ROBERT CANCRO
Journal: American Journal of Psychiatry (1970)

In an attempt to develop reliable criteria for symptoms unique to the schizophrenic syndromes, the author offers an Index of Formal Signs of thought disorder. Using the theory that language normally shows differentiation over time, he measures the form rather than the content of thought. The index was shown to be reliable when its ratings were compared with other clinical ratings.
TREATMENT OF NEURITIS BY ELECTROLYSIS
Authors: W. B. Jones
Journal: BMJ (1925)

\NEURITIS is sueli a colmmon disease, anid its treatment ofteni so unsatisfactory, that no apology is needed for referr iiig to treatmenit by electiolvsis, whiell gives good pliomise of relief in cases where th-e lesioni is of the initerstitial type, (Ine to inflammiiationi of the neive sheathi.This miiethiod w-as first published by Dr. iNauniitoni Davies,' and its use in sciatica has beeni described by Dr. E. A. GoUldei.2The apparatuls coInsists of a paHtostat, or simiiilar instruiimienit, with two electrodes, one being a large pad, which is applied to the arm or leg, and a smaller-pad or buttoni.An insulated needle, withi a platinllm point, is fixed in a liolder, and is -tsed for the actual treatment.In the absen-ce of an electric supply, a small inductioni coil can be used for the faradic current, and a battery of about a klozeni Leclanhele cells for the constant cur-rent.
Morphological and quantitative assessment of mast cells in rheumatoid arthritis associated non-specific interstitial pneumonia and usual interstitial pneumonia
Authors: S R Atkins
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> The role of mast cells in extra-articular manifestations of rheumatoid arthritis (RA) has not been studied so far. <b>Objective:</b> To characterise and quantify mast cells in RA associated interstitial pneumonia (IP) by an immunohistological study. <b>Methods:</b> Lung biopsy specimens from 15 patients with RA associated IP, 12 patients with idiopathic IP, and 5 control patients were stained with antibodies directed against tryptase (mast cell marker). Morphological characterisation of stained specimens was carried out and staining was quantified by computer assisted image analysis. <b>Results:</b> Tryptase staining showed the marked presence of mast cells in idiopathic IP and in RA associated IP. A significant difference in stained tissue area was found between RA associated IP (2.6%, IQR 2.0–3.2%, p = 0.015) and idiopathic IP (3.1%, IQR 1.8–3.7%, p = 0.003) compared with control tissue specimens (1.0%, IQR 0.7–1.5%). The extent of mast cell infiltration correlated well and inversely with pulmonary function variables. <b>Conclusions:</b> Mast cell infiltrates are present in RA associated IP and idiopathic IP. The observed correlation of pulmonary function and mast cell numbers would be consistent with the proposed role of mast cell mediators in the promotion of fibrogenesis. The findings provide a rationale for studying functional aspects of mast cell involvement in the pathogenesis of RA associated lung disease.
A peptide recognized by human cytolytic T lymphocytes on HLA-A2 melanomas is encoded by an intron sequence of the N-acetylglucosaminyltransferase V gene.
Authors: Y Guilloux, S Lucas, V G Brichard, A Van Pel, C Viret, E De Plaen, F Brasseur, B Lethé, F Jotereau, T Boon
Journal: The Journal of Experimental Medicine (1996)

A cytolytic T lymphocyte (CTL) clone that lyses many HLA-A2 melanomas was derived from a population of tumor-infiltrating lymphocytes of an HLA-A2 melanoma patient. The gene coding for the antigen recognized by this CTL was identified by transfection of a cDNA library. It is the gene which has been reported to code for N-acetylglucosaminyltransferase V (GnT-V). Remarkably, the antigenic peptide recognized by the CTL is encoded by a sequence located in an intron. In contrast to the fully spliced GnT-V mRNA, which was found in a wide range of normal and tumoral tissues, the mRNA containing the intron region coding for the antigen was not found at a significant level in normal tissues. This mRNA was observed to be present in about 50% of melanomas. Our results suggest that a promoter located near the end of the relevant intron is activated in melanoma cells, resulting in the production of an mRNA coding for the antigen.
New Strategies in Acute Lymphoblastic Leukemia: Translating Advances in Genomics into Clinical Practice
Authors: Charles G. Mullighan
Journal: Clinical Cancer Research (2010)

Abstract B-precursor acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy and remains a leading cause of death in children and young adults. Current therapeutic approaches involve intensive combination chemotherapy, which fails in up to one quarter of patients. New treatment approaches directed against rational therapeutic targets are required. Recent genomic profiling of ALL has identified several genetic alterations associated with a high risk of treatment failure. Deletion or sequence mutation of the lymphoid transcription factor gene IKZF1 (IKAROS) is associated with a high rate of leukemic relapse, and testing for IKZF1 alterations at diagnosis may aid risk stratification. A subset of B-ALL patients with IKZF1 alterations have a transcriptional profile similar to BCR-ABL1–positive ALL, and these patients commonly have novel rearrangements and mutations resulting in aberrant cytokine receptor signaling and activation of kinase signaling cascades, including rearrangement of CRLF2 and activating mutations of Janus kinases (JAK1 and JAK2). JAK inhibitor therapy is under investigation in children with relapsed and refractory malignancies, including leukemia. Clin Cancer Res; 17(3); 396–400. ©2010 AACR.
Distribution of Stresses and of Strain-Energy Density through the Wall Thickness in a Canine Aortic Segment
Authors: RAMESH N. VAISHNAV, JOHN T. YOUNG, DALI J. PATEL
Journal: Circulation Research (1973)

In this paper we presented a method for determining the distribution of circumferential ( S θ ), longitudinal ( S z ), and radial ( S r ) stress and of strain-energy density ( W ) in canine aortic segments under physiological loading. Aortic segments from 13 dogs were studied in vitro. Intraluminal pressure and longitudinal force were varied over ranges of 25 to 200 cm H 2 O and 0 to 100 g, respectively, and the external radius and the segment length were measured at each step. A nonlinear theory of large deformation of the aortic tissue based on the assumptions of incompressibility and curvilinear orthotropy was applied to the data. The 3, 7, or 12 constitutive constants of the theory were calculated without using the usual thin-wall assumption. These constants were then used to calculate the distribution of stresses and of W . The results indicated that (I) S θ , S z , S r , and W were largest in magnitude at the endothelial surface and decreased toward the adventitial surface, (2) the decrease was most marked in the inner third of the vessel wall, (3) in general S θ &gt; S z &gt; W &gt; S r , and (4) at a given longitudinal stretch an increase in intraluminal pressure increased S θ , S z , | S r |, and W , with the effect being most marked on S θ .
Achieving a Major Molecular Response at the Time of a Complete Cytogenetic Response (CCgR) Predicts a Better Duration of CCgR in Imatinib-Treated Chronic Myeloid Leukemia Patients
Authors: Ilaria Iacobucci, Giuseppe Saglio, Gianantonio Rosti, Nicoletta Testoni, Fabrizio Pane, Marilina Amabile, Angela Poerio, Simona Soverini, Simona Bassi, Daniela Cilloni, Renato Bassan, Massimo Breccia, Francesco Lauria, Barbara Izzo, Serena Merante, Francesco Frassoni, Stefania Paolini, Enrico Montefusco, Michele Baccarani, Giovanni Martinelli
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Most patients with chronic-phase chronic myeloid leukemia (CML) who receive imatinib achieve a complete cytogenetic remission (CCgR) and low levels of BCR-ABL transcripts. CCgR is durable in the majority of patients but relapse occurs in a subset. Experimental Design: To determine the potential of quantitative reverse transcription-PCR of BCR-ABL to predict cytogenetic relapse, we serially monitored residual disease in 97 CML patients with an imatinib-induced CCgR. Patients with late chronic phase CML after IFN-α failure were treated with imatinib (400 mg daily). Results: During the imatinib median follow-up time of 36 months (range, 12-54 months), disease monitoring occurred by cytogenetics and quantitative PCR. Twenty percent of patients experienced cytogenetic relapse at a median of 18 months after CCgR and a median of 24 months after starting imatinib. None of the possible prognostic factors studied in univariate and multivariate analyses seemed to predict for loss of cytogenetic response but the reduction of BCR-ABL transcript levels at the time of CCgR is an important prognostic factor. Conclusions: In our study, we showed not only that achieving a major molecular remission at 12 months is predictive of a durable cytogenetic remission but also that patients who achieved a major molecular remission (expressed both as the BCR-ABL/β2 microglobulin ratio % &amp;lt;0.0005 and as a 3-log reduction from median baseline value) already at the time of first achieving a CCgR have significantly longer cytogenetic remission durations than those without this magnitude of molecular response (P &amp;lt; 0.05).
CD157 in Ovarian Carcinoma: How Does It Help Us?
Authors: C. M. Annunziata, M. J. Birrer
Journal: JNCI Journal of the National Cancer Institute (2010)

CD157 is the second member of a family of nicotinamide adenine dinucleotidases that also includes CD38. These cell surface markers are ectoenzymes that cleave extracellular nicotinamide adenine dinucleotide to produce ADP-ribose and cyclic ADP-ribose at the cell surface. They also act as receptors for CD31 (aka “platelet – endothelial cell adhesion molecule-1”) expressed on endothelial cells. The signaling regulated by CD38 and CD157 may serve to regulate calcium homeostasis, as well as to modulate the function of poly-ADP ribosyl transferases involved in cell signaling, DNA repair, and apoptosis. In this issue of the Journal ( 1 ), Ortolan et al. present an intriguing story involving CD157 that suggests a role for this protein in the progression and aggressiveness of ovarian tumors. CD157 was detected in half of human primary ovarian cancers. Expression of CD157 was higher in primary tumors than in nonadherent ascites cells and was associated with more aggressive ovarian cancer, as refl ected by decreased overall patient survival. Exogenous expression of CD157 in an ovarian cancer cell line increased cell migration in a scratch assay in vitro. Conversely, inhibiting CD157 function with an antagonist antibody decreased migration, invasion, and adhesion of primary cultured ovarian cancer cells and ovarian cancer cell lines. These fi ndings were consistent with the known ability of CD157 to interact with CD31 on endothelial and stromal cells. What is the potential clinical utility of this observation? CD157 is anchored to the plasma membrane by glycophosphatidylinositol and can be shed into serum. In rheumatoid arthritis, high serum CD157 is associated with more severe joint destruction ( 2 ). Therefore, levels of CD157 could be potentially measured in the serum of ovarian cancer patients, as well as in the tumors themselves. CD157 is unlikely to be sensitive or specifi c enough as a biomarker for diagnosis of ovarian cancer but could confer increased invasive capacity to some ovarian cancers and therefore could indicate a particular line of therapy. CD157 was detected in ovarian cancers of each histology and may impart its function independent of histological classifi cation. Could CD157 be prognostic of outcome in ovarian cancer? In multiple myeloma and chronic lymphocytic leukemia, high CD157 in Ovarian Carcinoma: How Does It Help Us?
A novel mutation in ferroportin1 is associated with haemochromatosis in a Solomon Islands patient
Authors: K E Arden
Journal: Gut (2003)

A severe form of iron overload with the clinicopathological features of haemochromatosis inherited in an autosomal dominant manner has been described in the Solomon Islands. The genetic basis of the disorder has not been identified. The disorder has similarities to type 4 haemochromatosis, which is caused by mutations in ferroportin1.The aims of this study were to identify the genetic basis of iron overload in a patient from the Solomon Islands.Genomic DNA was isolated from peripheral blood leucocytes of a Solomon Islands man with severe iron overload. The entire coding region and splice sites of the ferroportin1 gene was sequenced.A novel missense mutation (431A>C; N144T) was identified in exon 5 of the ferroportin1 gene. A novel restriction endonuclease based assay which identifies both the N144T and N144H mutations was developed which will simplify the diagnosis and screening of patients for iron overload in the Solomon Islands and other populations. This is the first identified mutation associated with haemochromatosis in the Solomon Islands population.
F.R.C.S. in the Specialties
Authors: T. K. Lyle
Journal: BMJ (1964)

The central pattern generators (CPGs) for locomotion, located in the lumbar spinal cord, are functional at birth in the rat. Their maturation occurs during the last few days preceding birth, a period during which the first projections from the brainstem start to reach the lumbar enlargement of the spinal cord. The goal of the present study was to investigate the effect of suppressing inputs from supraspinal structures on the CPGs, shortly after their formation. The spinal cord was transected at the thoracic level at birth [postnatal day 0 (P0)]. We examined during the first postnatal week the capacity of the CPGs to produce rhythmic motor activity in two complementary experimental conditions. Left and right ankle extensor muscles were recorded <i>in vivo</i> during airstepping, and lumbar ventral roots were recorded <i>in vitro</i> during pharmacologically evoked fictive locomotion. Mechanical stimulation of the tail elicited long-lasting sequences of airstepping in the spinal neonates and only a few steps in sham-operated rats. <i>In vitro</i> experiments made simultaneously on spinal and sham animals confirmed the increased excitability of the CPGs after spinalization. A left–right alternating locomotor pattern was observed at P1–P3. Both types of experiments showed that the pattern was disorganized at P6–P7, and that the left–right alternation was lost. Alternation was restored after the activation of serotonergic 5-HT<sub>2</sub> receptors <i>in vivo</i>. These results suggest that descending pathways, in particular serotonergic projections, control the strength of reciprocal inhibition and therefore shape the locomotor pattern in the neonatal rat.