tbuckley/cabot-search huggingface dataset:
Respiratory symptoms and bronchial responsiveness are related to dietary salt intake and urinary potassium excretion in male children
Authors: R Pistelli, F Forastiere, GM Corbo, V Dell'Orco, G Brancato, N Agabiti, A Pizzabiocca, CA Perucci
Journal: European Respiratory Journal (1993)

To investigate whether dietary salt intake and urinary sodium and potassium levels are related to respiratory symptoms and bronchial responsiveness, a cross-sectional study among 2593 subjects aged 9 to 16 was conducted in four communities of the Latium region (Italy). Questionnaires were administered to the parents, urine samples were collected, lung function, methacholine challenge tests and prick tests were performed. Information about familial and personal dietary salt use and respiratory health was collected from the parents of 2439 (94%) subjects. A total of 2020 methacholine challenge tests and 916 urinary sodium and potassium levels were available for analysis. Personal table salt use was strongly related to cough and phlegm apart from colds (adjusted odds ratios, OR, 1.87, 95% confidence intervals, CI, 1.20-2.90), wheezing apart from colds (OR, 2.19, 95% CI, 1.27-3.77), wheezing with dyspnoea (OR, 1.45, 95% CI, 0.98-2.12) and wheezing after exercise (OR, 2.16, 95% CI, 1.35-3.44). These associations were mainly found in boys. Use of familial table salt and canned food showed no relation to respiratory symptoms. Increased bronchial responsiveness was associated with a higher urinary potassium excretion in boys, but not with urinary sodium. In conclusion, personal table salt use is related to an increased prevalence of bronchial symptoms; an increase in bronchial responsiveness among those with higher potassium excretion also seems to be implied. Although it is difficult to interpret the results of this study in causal terms, the findings might be relevant to the distribution of bronchial symptoms and diseases in the population.
Eosinophil peroxidase-induced mast cell secretion.
Authors: W R Henderson, E Y Chi, S J Klebanoff
Journal: The Journal of Experimental Medicine (1980)

Eosinophil peroxidase (EPO) at relatively low levels (4-30 mU), when supplemented with H2O2 and a halide, induced mast cell degranulation. Histamine release occurred without concomitant release of the cytoplasmic marker lactic dehydrogenase (LDH), and this, together with ultrastructural studies, indicated a noncytotoxic effect comparable with that induced by other mast cell secretagogues. At pH 7.4, iodide was effective at concentrations down to 10(-5) M, and although chloride alone was ineffective at 0.1 M, a combination of 0.1 M chloride and 10(-6) iodide could meet the halide requirement. Chloride alone was effective at pH 6.5 and 6.0. EPO could be replaced by myeloperoxidase. When the EPO level was increased to 100 mU, combination with H2O2- and iodide-induced cytotoxic histamine release as indicated by concomitant LDH release and ultrastructural evidence of cell disruption. This cytotoxic response reverted to a secretory one on the addition of albumin. Peroxidase was detected on the surface of extruded granules by diaminobenzidine cytochemistry. The mast cell granule (MCG)/EPO complex when supplemented with H2O2 and iodide was more effective than free EPO in the stimulation of mast cell secretion. The stimulation of mast cell mediator release by the EPO-H2O2-halide system and the formation of MCG/EPO complexes with augmented cytotoxic activity may influence the adjacent inflammatory response.
EPITHELIOMATOUS ULCERATION AMONG TAR WOKERS
Authors: W. J. O'DONOVAN
Journal: British Journal of Dermatology (1920)

THE increafiing impoi'tance tliat is beiug attached to the iiiduwtrial setiology of disease is reflected in the increasing number of occupational diseases that are being made notifiable to the Home Office Ijy successive orders of the Secretary of Stiite for Home Affairs.The latest to be i.ssued under Section 73 of tlie Factory and Workshop Act, 1901, is dated November 28th, 1919, and brings " epithelioinatous nlceration due to tar " within its }»rovisiuns as from January l.--t uf this year :In pursuance of Sub-section 4 of Section 73 of tlie Factory ami Wotlcsliop Act, ]901, I hereby apply the provisiojis of the said section to all cases of-((.()epithehoinatuus ifJceration due to tar, pitch, bitumen, mhieral oil or paraffin, or any compound, product or residue of any of these substances, and (/;) chrome uheratioti, that is, nlt'eration due to chromic ucid or bichromate of potassium, sodium or amumiiiiun or any preparatiou uf tliese substancesoccurring in a factory or work.sliop.This Order shall come into furce on tbe 1st day of Jauuary, 19'20.E. SHORTT,
Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes
Authors: H. Bradley Nuss, Eduardo Marbán, David C. Johns
Journal: Journal of Clinical Investigation (1999)

The high incidence of sudden death in heart failure may reflect abnormalities of repolarization and heightened susceptibility to arrhythmogenic early afterdepolarizations (EADs). We hypothesized that overexpression of the human K+ channel HERG (human ether-a-go-go-related gene) could enhance repolarization and suppress EADs. Adult rabbit ventricular myocytes were maintained in primary culture, which suffices to prolong action potentials and predisposes to EADs. To achieve efficient gene transfer, we created AdHERG, a recombinant adenovirus containing the HERG gene driven by a Rous sarcoma virus (RSV) promoter. The virally expressed HERG current exhibited pharmacologic and kinetic properties like those of native IKr. Transient outward currents in AdHERG-infected myocytes were similar in magnitude to those in control cells, while stimulated action potentials (0.2 Hz, 37°C) were abbreviated compared with controls. The occurrence of EADs during a train of action potentials was reduced by more than fourfold, and the relative refractory period was increased in AdHERG-infected myocytes compared with control cells. Gene transfer of delayed rectifier potassium channels represents a novel and effective strategy to suppress arrhythmias caused by unstable repolarization.
Mr. Lucas on Stammering, and its Cure by Operation
Authors: P. B. Lucas
Journal: BMJ (1841)

CURE OF STUTTERING.' 389 ture towards the inner cantlhus, and so applied, because the pupil appears to approach the object, and to keep it constantly iII viCw.The term repulaion is applied to that movement of the cornea wrhich tak-es place in an opposite direction; that is, from the inner canthus towards the centre of the palpebral aperture; here the ptupil will, during a part of its course, turn from the object, and thus we acquire the term repulsion.In conclusion, if an internal rectus muscle, of an eye affected with strabismus convergens, or of a straight eye, is about to be divided, let the surgeon ascertain if either eye be repelled beyond its centre; for as certainly as the muscle is divided, so will be the unnatural divergence of the eye which was repelled previous to operation.In many cases of convevment strabismus, it is frequently found that no sign of repulsion can be detected previously to the first operation; but that on the division of one muscle there will be a distinct evidence of its existence, even, perhaps, to extreme repulsion; thouglh more frequently the repulsion is not central, and theretore need not prevqit the performance of the second operation, after whicli the repulsion is sure to be increased.I hope that after what has been stated, no surgeon will in future hazard his reputation with his patient by neg- lecting carefully 'to examine and search for this signi of eversion, or that he will fail to wmrn his patient of the probable result of dividing an inner rectus, either for the commencement or perfecting of a case of convergent stra- bismus.-Iam, Gentlemen, your obedient servant,
Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function
Authors: Françoise Haeseleer, Yoshikazu Imanishi, Tadao Maeda, Daniel E Possin, Akiko Maeda, Amy Lee, Fred Rieke, Krzysztof Palczewski
Journal: Nature Neuroscience (2004)
Antibody repertoire against the A60 antigen complex during the course of pulmonary tuberculosis
Authors: M Amicosante, G Paone, F Ameglio, E L Bianchi, E Piccolella, L Richeldi, A Bisetti, M Luisetti, C Saltini
Journal: European Respiratory Journal (1993)

The A60 antigen complex is a Mycobacterium bovis (BCG) highly immunodominant antigen containing both B and T-cell epitopes. Clinical-serological studies show that elevated anti-A60 titres are present during tuberculosis. We wished to analyze in detail antibody responses against A60 components during the course of tuberculosis. A mixed longitudinal study was designed including individuals at the onset of tuberculosis, during treatment and after resolution of the disease. The anti-A60 repertoire was analyzed using a western blot assay with A60 as the antigen. While PPD- normals recognized only the 65 kDa heat shock protein (HSP), PPD+ normal individuals displayed low levels of anti-A60 antibodies against dominant antigens. There were immunoglobulin M (IgM) and immunoglobulin G (IgG) consistent with response to a latent infection. Onset tuberculosis was characterized by IgM and IgG antibodies against 52 to 28 kDa antigens; IgM response being limited to earlier phases of the disease. In contrast, IgM antibodies against 25 to 14 kDa antigens appeared only 2-6 months after disease onset. The antibody repertoire of chemotherapy-treated, resolved tuberculosis was exclusively IgG in isotype, as for a memory-type response. Thus, western blot analysis with A60 identifies typical antibody patterns associated with different clinical phases of tuberculosis infection. Such approach may help in identifying new single antigens for serologic diagnosis of active tuberculosis.
A large scale expression study associates uc.283-plus lncRNA with pluripotent stem cells and human glioma
Authors: Marco Galasso, Paola Dama, Maurizio Previati, Sukhinder Sandhu, Jeff Palatini, Vincenzo Coppola, Sarah Warner, Maria E Sana, Riccardo Zanella, Ramzey Abujarour, Caroline Desponts, Michael A Teitell, Ramiro Garzon, George Calin, Carlo M Croce, Stefano Volinia
Journal: Genome Medicine (2014)

There are 481 ultra-conserved regions (UCRs) longer than 200 bases in the genomes of human, mouse and rat. These DNA sequences are absolutely conserved and show 100% identity with no insertions or deletions. About half of these UCRs are reported as transcribed and many correspond to long non-coding RNAs (lncRNAs).We used custom microarrays with 962 probes representing sense and antisense sequences for the 481 UCRs to examine their expression across 374 normal samples from 46 different tissues and 510 samples representing 10 different types of cancer. The expression in embryonic stem cells of selected UCRs was validated by real time PCR.We identified tissue selective UCRs and studied UCRs in embryonic and induced pluripotent stem cells. Among the normal tissues, the uc.283 lncRNA was highly specific for pluripotent stem cells. Intriguingly, the uc.283-plus lncRNA was highly expressed in some solid cancers, particularly in one of the most untreatable types, glioma.Our results suggest that uc.283-plus lncRNA might have a role in pluripotency of stem cells and in the biology of glioma.
Thrombocytopenia in homosexual men
Authors: Howard G. Goldsweig, Ronald Grossman, Daniel William
Journal: American Journal of Hematology (1986)

Abstract The office records of two private practices with a preponderance of homosexual patients were reviewed for cases of males with unexplained thrombocytopenia. Twenty‐five patients meeting the selection criteria were found. The clinical and laboratory features of these patients were reviewed and compared to those characteristically seen in classic autoimmune thrombocytopenic purpura. The mean age of the group was 36.5 years. There was a high incidence of a history of sexually transmitted diseases. Sixty percent had another hematologic abnormality in addition to thrombocytopenia. The clinical outcomes for these 25 patients were as follows: eight (32%) had a spontaneous increase in platelets; four (16%) had a stable count not requiring therapy; 12 (48%) received high‐dose prednisone; seven (28%) failed predinosone therapy and went on to splenectomy; two (8%) subsequently developed CDC‐defined AIDS.
Worsening of pain and function over 5 years in individuals with ‘early’ OA is related to structural damage: data from the Osteoarthritis Initiative and CHECK (Cohort Hip &amp; Cohort Knee) study
Authors: Janet Wesseling, Sita M A Bierma-Zeinstra, Margreet Kloppenburg, Rik Meijer, Johannes W J Bijlsma
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To analyse the relation of joint damage on evolution of pain and physical functioning in two different cohorts of early phase of osteoarthritis (OA): Osteoarthritis Initiative (OAI) and Cohort Hip &amp; Cohort Knee study (CHECK). <h3>Methods</h3> Longitudinal data of 4–5 years follow-up (= medium term) of CHECK study and OAI were used. The Western Ontario and McMaster Universities of Osteoarthritis Index (WOMAC) was used to measure pain and physical functioning. For comparison with CHECK a subgroup of the OAI Incidence cohort was selected, Generalised estimating equations were used and all models were adjusted for gender, Body Mass Index, age, amount of working hours, racial background and hip pain at baseline. Finally, an interaction term was added to assess a possible differential effect of radiological progression on evolution of pain and function in the two cohorts. <h3>Results</h3> At baseline, CHECK had less radiographic OA (K&amp;L ≥2) compared with the OAI Incidence subgroup, but at follow-up CHECK had more radiographic change (51% vs 15% ≥1 K&amp;L point increase; p&lt;0.001). Over 4 years of follow-up, evolution of pain and physical functioning remained fairly stable in both cohorts, however, at different levels, OAI participants had less pain and less problems with physical functioning compared to CHECK participants. Both cohorts showed the same negative effect of rapid radiological change (K&amp;L change of 2 points) on pain and physical function. <h3>Conclusions</h3> In participants with 'early symptomatic OA' rapid radiological change (change of ≥2 grades of K&amp;L in 4 or 5 years) is related to worsening of pain and function
Cellular Mechanisms of Contractile Dysfunction in Hibernating Myocardium
Authors: Virginie Bito, Frank R. Heinzel, Frank Weidemann, Christophe Dommke, Jolanda van der Velden, Erik Verbeken, Piet Claus, Bart Bijnens, Ivan De Scheerder, Ger J.M. Stienen, George R. Sutherland, Karin R. Sipido
Journal: Circulation Research (2004)

Ischemic heart disease is a leading cause of chronic heart failure. Hibernation (ie, a chronic reduction of myocardial contractility distal to a severe coronary stenosis and reversible on revascularization) is an important contributing factor. The underlying cellular mechanisms remain however poorly understood. In young pigs (n=13, ISCH), an acquired coronary stenosis >90% (4 to 6 weeks) resulted in the development of hibernating myocardium. Single cardiac myocytes from the ISCH area were compared with cells from the same area obtained from matched normal pigs (n=12, CTRL). Myocytes from ISCH were larger than from CTRL. In field stimulation, unloaded cell shortening was reduced and slower in ISCH; relaxation was not significantly different. The amplitude of the [Ca2+]i transient was not significantly reduced, but reducing [Ca2+]o for CTRL cells could mimic the properties of ISCH, inducing a significant reduction of contraction, but not of [Ca2+]i. Action potentials were longer in ISCH. With square voltage-clamp pulses of equal duration in ISCH and CTRL, the amplitude of the [Ca2+]i transient was significantly smaller in ISCH, as was the Ca2+ current. Near-maximal activation of the myofilaments resulted in smaller contractions of ISCH than of CTRL cells. There was no evidence for increased degradation of Troponin I. In conclusion, cellular remodeling is a major factor in the contractile dysfunction of the hibernating myocardium. Myocytes are hypertrophied, action potentials are prolonged, and L-type Ca2+ currents and Ca2+ release are decreased. The steep [Ca2+]i dependence of contraction and possibly a reduction of maximal myofilament responsiveness further enhance the contractile deficit.
Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study
Authors: Alex Iranzo, Francisco Lomeña, Heike Stockner, Francesc Valldeoriola, Isabel Vilaseca, Manel Salamero, Jose Luis Molinuevo, Monica Serradell, Joan Duch, Javier Pavía, Judith Gallego, Klaus Seppi, Birgit Högl, Eduard Tolosa, Werner Poewe, Joan Santamaria
Journal: The Lancet Neurology (2010)
A Critical Analysis of the Interplay between Cytochrome P450 3A and P-Glycoprotein: Recent Insights from Knockout and Transgenic Mice
Authors: Robert A. B. van Waterschoot, Alfred H. Schinkel
Journal: Pharmacological Reviews (2011)

CYP3A is one of the most important drug-metabolizing enzymes, determining the first-pass metabolism, oral bioavailability, and elimination of many drugs. It is also an important determinant of variable drug exposure and is involved in many drug-drug interactions. Recent studies with CYP3A knockout and transgenic mice have yielded a number of key insights that are important to consider during drug discovery and development. For instance, studies with tissue-specific CYP3A-transgenic mice have highlighted the importance of intestinal CYP3A-dependent metabolism. They also revealed that intestinal CYP3A plays an important role in the regulation of various drug-handling systems in the liver. Intestinal CYP3A activity can thus have far-reaching pharmacological effects. Besides CYP3A, the active drug efflux transporter P-glycoprotein also has a strong effect on the pharmacokinetics of numerous drugs. CYP3A and P-glycoprotein have an extensive overlap in their substrate spectrum. It has been hypothesized that for many drugs, the combined activity of CYP3A and P-glycoprotein makes for efficient intestinal first-pass metabolism of orally administered drugs as a result of a potentially synergistic collaboration. However, there is only limited in vitro and in vivo evidence for this hypothesis. There has also been some confusion in the field about what synergy actually means in this case. Our recent studies with Cyp3a/P-glycoprotein combination knockout mice have provided further insights into the CYP3A-P-glycoprotein interplay. We here present our view of the status of the synergy hypothesis and an attempt to clarify the existing confusion about synergy. We hope that this will facilitate further critical testing of the hypothesis and improve communication among researchers. Above all, the recent findings and insights into the interplay between CYP3A and P-glycoprotein may have implications for improving oral drug bioavailability and reducing adverse side effects.
Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract
Authors: Michael CW Chan, Renee WY Chan, Louisa LY Chan, Chris KP Mok, Kenrie PY Hui, Joanne HM Fong, Kin P Tao, Leo LM Poon, John M Nicholls, Y Guan, JS Malik Peiris
Journal: The Lancet Respiratory Medicine (2013)

BackgroundSince March, 2013, an avian-origin influenza A H7N9 virus has caused severe pneumonia in China. The aim of this study was to investigate the pathogenesis of this new virus in human beings.MethodsWe obtained ex-vivo cultures of the human bronchus, lung, nasopharynx, and tonsil and in-vitro cultures of primary human alveolar epithelial cells and peripheral blood monocyte-derived macrophages. We compared virus tropism and induction of proinflammatory cytokine responses of two human influenza A H7N9 virus isolates, A/Shanghai/1/2013 and A/Shanghai/2/2013; a highly pathogenic avian influenza H5N1 virus; the highly pathogenic avian influenza H7N7 virus that infected human beings in the Netherlands in 2003; the 2009 pandemic influenza H1N1 virus, and a low pathogenic duck H7N9 virus that was genetically different to the human disease causing A H7N9 viruses.FindingsBoth human H7N9 viruses replicated efficiently in human bronchus and lung ex-vivo cultures, whereas duck/H7N9 virus failed to replicate in either. Both human A H7N9 viruses infected both ciliated and non-ciliated human bronchial epithelial cells and replicated to higher titres than did H5N1 (p<0·0001 to 0·0046) and A/Shanghai/1/2013 replicated to higher titres than did H7N7 (p=0·0002–0·01). Both human A H7N9 viruses predominantly infected type II alveolar epithelial cells and alveolar macrophages in the human lung and replicated to higher titres than did H5N1 (p<0·0001 to 0·0078); A/Shanghai/1/2013 replicated to higher titres than did H1N1 (p=0·0052–0·05) and H7N7 (p=0·0031–0·0151). Human H7N9 viruses were less potent inducers of proinflammatory cytokines compared with H5N1 virus.InterpretationCollectively, the results suggest that the novel H7N9 viruses are better adapted to infect and replicate in the human conducting and lower airways than are other avian influenza viruses, including H5N1, and pose an important pandemic threat.FundingArea of Excellence Scheme of the University Grants Committee (AoE/M-12/96), Hong Kong Special Administrative Region.
The role of Ia molecules in the activation of T lymphocytes. III. Antigen-specific, Ia-restricted, interleukin 2-producing T cell hybridomas with detectable affinity for the restricting I-A molecule.
Authors: K L Rock, B Benacerraf
Journal: The Journal of Experimental Medicine (1983)

Antigen-specific I region-restricted, interleukin 2-producing T cell hybridomas were produced by fusing GAT-specific T cell blasts with BW5147. Two antigen-specific phenotypes were identified, one autoreactive and one nonautoreactive. All of the antigen-specific and autoreactive clones were H-2 restricted, mapping to the IA subregion by genetic analysis and monoclonal antibody inhibition. Both the antigen-specific and autoreactive stimulation are the property of a single cell and required no known exogenous antigens.