tbuckley/cabot-search huggingface dataset:
Immune cells control skin lymphatic electrolyte homeostasis and blood pressure
Authors: Helge Wiig, Agnes Schröder, Wolfgang Neuhofer, Jonathan Jantsch, Christoph Kopp, Tine V. Karlsen, Michael Boschmann, Jennifer Goss, Maija Bry, Natalia Rakova, Anke Dahlmann, Sven Brenner, Olav Tenstad, Harri Nurmi, Eero Mervaala, Hubertus Wagner, Franz-Xaver Beck, Dominik N. Müller, Dontscho Kerjaschki, Friedrich C. Luft, David G. Harrison, Kari Alitalo, Jens Titze
Journal: Journal of Clinical Investigation (2013)

The skin interstitium sequesters excess Na+ and Cl- in salt-sensitive hypertension. Mononuclear phagocyte system (MPS) cells are recruited to the skin, sense the hypertonic electrolyte accumulation in skin, and activate the tonicity-responsive enhancer-binding protein (TONEBP, also known as NFAT5) to initiate expression and secretion of VEGFC, which enhances electrolyte clearance via cutaneous lymph vessels and increases eNOS expression in blood vessels. It is unclear whether this local MPS response to osmotic stress is important to systemic blood pressure control. Herein, we show that deletion of TonEBP in mouse MPS cells prevents the VEGFC response to a high-salt diet (HSD) and increases blood pressure. Additionally, an antibody that blocks the lymph-endothelial VEGFC receptor, VEGFR3, selectively inhibited MPS-driven increases in cutaneous lymphatic capillary density, led to skin Cl- accumulation, and induced salt-sensitive hypertension. Mice overexpressing soluble VEGFR3 in epidermal keratinocytes exhibited hypoplastic cutaneous lymph capillaries and increased Na+, Cl-, and water retention in skin and salt-sensitive hypertension. Further, we found that HSD elevated skin osmolality above plasma levels. These results suggest that the skin contains a hypertonic interstitial fluid compartment in which MPS cells exert homeostatic and blood pressure-regulatory control by local organization of interstitial electrolyte clearance via TONEBP and VEGFC/VEGFR3-mediated modification of cutaneous lymphatic capillary function.
A Common Variant at 9p21 Is Associated With Sudden and Arrhythmic Cardiac Death
Authors: Christopher Newton-Cheh, Nancy R. Cook, Martin VanDenburgh, Eric B. Rimm, Paul M. Ridker, Christine M. Albert
Journal: Circulation (2009)

Although a heritable basis for sudden cardiac death (SCD) is suggested by the impact of family history on SCD risk, common genetic determinants have been difficult to identify. We hypothesized that a common variant at chromosome 9p21 related to myocardial infarction would influence SCD risk.This was a prospective, nested, case-control analysis among individuals of European ancestry enrolled in 6 prospective cohort studies. Study subjects were followed up for development of SCD, and genotypes for rs10757274 were determined for 492 sudden and/or arrhythmic deaths and 1460 controls matched for age, sex, cohort, history of cardiovascular disease, and follow-up time. Conditional logistic regression with fixed-effects meta-analysis assuming an additive model was used to test for associations. When individual study results were combined in the meta-analysis, each increasing copy of the G allele at rs10757274 conferred a significantly elevated age-adjusted odds ratio for SCD of 1.21 (95% confidence interval, 1.04 to 1.40; P=0.01). Controlling for cardiovascular and lifestyle risk factors strengthened these relationships (odds ratio, 1.29 per G-allele copy; 95% confidence interval, 1.09 to 1.53; P=0.003). These results were not materially altered in sensitivity analyses limited to definite SCD, in models that further controlled for the development of interim cardiovascular disease, or when the highly correlated variant rs2383207 was tested.The major allele of a single-nucleotide polymorphism previously associated with increased risk of coronary artery disease events is associated with increased risk of SCD in individuals of European ancestry. Study of the mechanism underlying this association may improve our understanding of lethal cardiovascular disease.
Small facial haemangioma and supraumbilical raphe-a forme fruste of PHACES syndrome?
Authors: Y-C. Chan, L.F. Eichenfield, J. Malchiodi, S.F. Friedlander
Journal: British Journal of Dermatology (2005)

We report two female infants with congenital midline supraumbilical raphes who subsequently developed haemangiomas on the lower lip and gingiva within the first 2 months of life. One was found to have a subglottic haemangioma during laryngoscopy. The infants were otherwise well and had normal chest X-ray, echocardiogram, cranial ultrasound, magnetic resonance imaging/angiography (head, neck, chest) and ophthalmological examination. Both received oral prednisolone 1-2 mg kg(-1) daily and four sessions of flashlamp pulsed-dye laser therapy to the lip lesions, with significant improvement. The initial presentation of these two infants with supraumbilical raphes, who were otherwise healthy and without other cutaneous stigmata, suggested the diagnosis of isolated congenital sternal malformation. However, lower lip and gingival haemangiomas developed 4-6 weeks later, consistent with the diagnosis of PHACES syndrome. Children with sternal malformation and haemangioma may also have intracranial and/or cardiovascular anomalies. All previously reported patients were females who had either craniofacial and/or multiple haemangiomas. We propose guidelines for the evaluation and management of a neonate presenting with a sternal fusion defect at birth.
<i>PHOX2B</i> Germline and Somatic Mutations in Late-Onset Central Hypoventilation Syndrome
Authors: Delphine Trochet, Loïc de Pontual, Christian Straus, David Gozal, Ha Trang, Pierre Landrieu, Arnold Munnich, Stanislas Lyonnet, Claude Gaultier, Jeanne Amiel
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Late-onset central hypoventilation syndrome (LO-CHS) is a rare disorder that may manifest as early as infancy or as late as during adulthood. The potential overlap of LO-CHS with congenital CHS is under debate, even though both disorders can result from heterozygous PHOX2B gene mutations.Objectives: To characterize the PHOX2B status in a series of 25 patients with LO-CHS referred from 3 months of age to adulthood. Whenever a PHOX2B mutation was identified, we ascertained its germline or somatic origin in both patients with LO-CHS and in 15 parents of probands with congenital CHS found to harbor a PHOX2B mutation.Methods: The PHOX2B gene was analyzed by direct DNA sequencing and origin of the mutation evaluated by fluorescent PCR.Measurements and Main Results: We have identified a heterozygous PHOX2B gene mutation in 17 of 25 patients with LO-CHS. The far most frequent mutation results in a germline +5 alanine expansion in the series of 20 alanines (15 cases) that show incomplete penetrance and variable expressivity, possibly resulting from combined environmental and genetic factors. PHOX2B frameshift and missense mutations have also been identified in patients with LO-CHS. Importantly, one parent found to harbor a somatic mosaic for a +8 alanine expansion developed alveolar hypoventilation in his 40s.Conclusions: These data indicate that PHOX2B gene mutations should be systematically examined in any adult with unexplained central hypoventilation and raise the question of follow-up for apparently healthy parents found to harbor a somatic mosaic for the PHOX2B mutation identified in their child.
Recent advances: care of near term infants with respiratory failure
Authors: K. J Barrington, N. N Finer
Journal: BMJ (1997)

Postgraduate training programmes for family medicine are developing simultaneously in many different parts of the world. In the UK continuity of care is highly valued but vocational training schemes have not been able to provide continuity of care for patients throughout a three-year training course. In Puerto Rico a vocational training scheme exists in which residents are enabled to integrate their hospital and family practice work throughout a three-year course. This arrangement is described and compared and contrasted with vocational training in the UK.
Anti-Fab antibodies in humans. Predominance of minor immunoglobulin G subclasses in rheumatoid arthritis.
Authors: J E Persselin, R H Stevens
Journal: Journal of Clinical Investigation (1985)

Isoelectric focusing analyses of sera from patients with rheumatoid arthritis (RA) demonstrate two populations of antibodies directed against the Fab portion of pooled human IgG. One population is composed of polyclonal alkaline anti-Fab antibodies (alpha FABA) and the other, acidic alpha FABA which are more clonally restricted. In this study we have identified the immunoglobulin classes and subclasses of these antibodies in RA sera. Enzyme-linked immunosorbent assays (ELISA) demonstrated alpha FABA in RA sera to be predominantly IgG. A large portion of IgG alpha FABA existed as immune complexes, inasmuch as dialysis of RA sera against 6 M urea before ELISA analysis was necessary for maximal detection of alpha FABA activity. Chromatofocusing of RA sera isolated alpha FABA of different charges and revealed the acidic clonally restricted alpha FABA to be IgG4 and IgG3, whereas the polyclonal alkaline group contained IgG1, IgG2, and IgG3. Overall, acidic IgG3 and IgG4 comprised 70% of IgG alpha FABA, and high levels of IgG4 were seen in most RA sera. When alpha FABA were elevated in normal sera, they were primarily of the IgG4 subclass, and also existed as immune complexes. Serum anti-Fab activity was removed by adsorption of sera with Fab fragments. Anti-Fab antibodies of both kappa and lambda light-chain types were present in RA sera, and F(ab')2 fragments of RA serum immunoglobulin were found to possess anti-Fab activity. These studies indicate that alpha FABA in RA sera are limited to the IgG class, and that most of these antibodies exist as immune complexes and display clonal and minor IgG subclass restriction.
Deflazacort protects against late‐phase but not early‐phase reactions induced by the allergen‐specific conjunctival provocation test
Authors: G. Ciprandi, S. Buscaglia, G. P. Pesce, A. Iudice, M. Bagnasco, G. W. Canonica
Journal: Allergy (1993)

The protective effects of deflazacort against the inflammation that follows the conjunctival provocation test (CPT) by specific allergen were assessed in 24 patients with rhinoconjunctivitis caused by Parietaria judaica in a double‐blind study. After a screening CPT, patients were randomized into four treatment groups, each being given deflazacort (oral tablets) at 6, 30, and 60 mg once daily, or matching placebo, for 3 d, outside the pollen season. Clinical evaluation (itching, hyperemia, lacrimation, and swelling of eyelids) and cytologic assessment (number of inflammatory cells in conjunctival scraping and evaluation of ICAM (intercellular adhesion molecule)‐1/CD54 expression on epithelial cells) were performed at base line, 30 min (early‐phase reaction (EPR), 6 h and 24 h (late‐phase reaction (LPR)) after specific CPT, and before and after treatment. Neither the EPR clinical reactions nor the EPR total number of inflammatory cells was modified by deflazacort. However, the LPR clinical effects were significantly reduced by deflazacort at 30 or 60mg/d ( P &lt;0.01), as compared with placebo. The total number of inflammatory cells during LPR was significantly reduced by deflazacort at 30 or 60 nig/d (( P &lt;0.01), as compared with placebo. Furthermore, CD54 expression was significantly reduced by deflazacort at 30 or 60 mg/d both in the EPR (( P &lt;0.01) and LPR (( P &lt;0.01), as compared with placebo. None of the studied indicators were modified at the 6 mg/d dose. This study shows that deflazacort has a highly protective action against clinical and cellular LPR effects induced by the specific CPT, In addition, deflazacort markedly reduces CD54 expression on the conjunctival epithelium during both EPR and LPR.
Pseudotumor Cerebri and Low Vitamin-A Intake
Authors: C. Edmunds
Journal: JAMA (1973)

To the Editor.—  Vitamin A-induced pseudotumor cerebri, or benign intracranial hypertension, is infrequent in adults and usually occurs in individuals taking high doses of Vitamin A for dermatologic conditions, occasionally in food faddists who consume large quantities of various vitamin preparations, and occasionally in those who take it in hopes of improving their vision or preventing colds.  A recent review 1 cited 17 cases of vitamin-A intoxication in adults and adolescents following two months to nine years of vitamin A ingestion at daily dosages of 41,000 to 600,000 units. Approximately half the cases had intracranial hypertension. We report a probable case of such vitamin-A intoxication following the ingestion of 25,000 units of vitamin A six days a week for eight months, an amount frequently prescribed or taken unnecessarily without a prescription.  Report of a Case.—  A 33-year-old white woman was seen with bilateral papilledema. Two and a half years previously she
IS EYESTRAIN EVER AN ETIOLOGIC FACTOR IN EPILEPSY?
Authors: H. O. REIK
Journal: JAMA (1907)

In reporting the following four cases of epilepsy in which the active causative agent appears to have been eyestrain and in which correction of the refraction errors relieved the greater affection, I am actuated by a desire to aid in promoting the educational work that other ophthalmologists have been doing in this direction, and possibly to benefit some other sufferers, rather than to enter into the dispute regarding the relationship of eyestrain to epilepsy. My own observations convince me that an epileptic seizure may be induced by reflex action from an ocular disease. There may be some physicians who do not want to be convinced of this, there are certainly some who deny the possibility of the eyes playing any important part in connection with epilepsy, and the great mass of the profession has probably never given any consideration to the matter and would have no answer prepared for the
Regulatory T cells control the Th1 immune response in murine crescentic glomerulonephritis
Authors: Hans-Joachim Paust, Annett Ostmann, Annette Erhardt, Jan-Eric Turner, Joachim Velden, Hans-Willi Mittrücker, Tim Sparwasser, Ulf Panzer, Gisa Tiegs
Journal: Kidney International (2011)

Crescentic glomerulonephritis is mediated by inappropriate humoral and cellular immune responses toward self-antigens that may result from defects in central and peripheral tolerance. Evidence now suggests that regulatory T cells (Tregs) may be of pathophysiological importance in proliferative and crescentic forms of glomerulonephritis. To analyze the role of endogenous Tregs in a T cell-dependent glomerulonephritis model of nephrotoxic nephritis, we used 'depletion of regulatory T cell' (DEREG) mice that express the diphtheria toxin receptor under control of the FoxP3 (forkhead box P3) gene promoter. Toxin injection into these mice efficiently depleted renal and splenic FoxP3(+) Treg cells as determined by fluorescent-activated cell sorting (FACS) and immunohistochemical analyses. Treg depletion exacerbated systemic and renal interferon-γ (IFNγ) expression and increased recruitment of IFNγ-producing Th1 cells into the kidney without an effect on the Th17 immune response. The enhanced Th1 response, following Treg cell depletion, was associated with an aggravated course of glomerulonephritis as measured by glomerular crescent formation. Thus, our results establish the functional importance of endogenous Tregs in the control of a significantly enhanced systemic and renal Th1 immune response in experimental glomerulonephritis.
Topical 0.05% betamethasone dipropionate: efficacy in psoriasis with once a day vs. twice a day application
Authors: S. Singh, J. Gopal, R.N. Mishra, S.S. Pandey
Journal: British Journal of Dermatology (1995)

Journal Article Topical 0.05% betamethasone dipropionate: efficacy in psoriasis with once a day vs. twice a day application Get access S. Singh, S. Singh Department of Dermatology, Institute of Medical Sciences, Banaras Hindu University, Varanasi‐221 005, India Search for other works by this author on: Oxford Academic Google Scholar J. Gopal, J. Gopal Department of Dermatology, Institute of Medical Sciences, Banaras Hindu University, Varanasi‐221 005, India Search for other works by this author on: Oxford Academic Google Scholar R.N. Mishra, R.N. Mishra Department of Preventive and Social Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi‐221 005, India Search for other works by this author on: Oxford Academic Google Scholar S.S. Pandey S.S. Pandey Department of Dermatology, Institute of Medical Sciences, Banaras Hindu University, Varanasi‐221 005, India Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 3, 1 September 1995, Pages 497–498, https://doi.org/10.1111/j.1365-2133.1995.tb02693.x Published: 01 September 1995
Correction: Conference on Obesity
Authors: MAYER B. DAVIDSON
Journal: Annals of Internal Medicine (1973)

Letters, Comments, and Corrections1 February 1973Correction: Conference on ObesityMAYER B. DAVIDSON, M.D.MAYER B. DAVIDSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-2-315_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I wish to correct two errors that appeared in the recent UCLA conference on obesity (Ann Intern Med77:797-805, 1972). The insulin sensitivity test in mice (Figure 6) was done by Dr. Richard Mahler (MAHLERRJ, SZABOO: Amelioration of insulin resistance in obese mice.Am J Physiol221:980-983, 1971). The correct reference was given in the text, but apparently in rearranging references from three contributors, the wrong one appeared in the figure. A minor error appeared in Figure 5, where it is implied that the significant correlation between fat cell diameter and weight index was obtained... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine UCLA School of Medicine Los Angeles, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1973Volume 78, Issue 2Page: 315-315KeywordsAdipocytesInsulin resistanceObesityOverweight Issue Published: 1 February 1973 PDF DownloadLoading ...
Clinical and Bacteriologic Studies of the Effect of Massive Doses of Penicillin G on Infections Caused by Gram-Negative Bacilli
Authors: Louis Weinstein, Phillip I. Lerner, William H. Chew
Journal: New England Journal of Medicine (1964)

INFECTIONS due to gram-negative bacilli are presently increasing in frequency and difficulty of management. One approach to the therapy of this type of disease has been a search for and development of more effective antimicrobial compounds. Another possibility that has received little attention is the use of some of the "old" antibiotics in doses higher than those conventionally employed. When penicillin G was first used clinically, the limited quantities available dictated its application in situations involving highly "sensitive" organisms (1 to 2 units per milliliter) such as pneumococci, Streptococcus pyogenes, penicillinase-negative staphylococci and some strains of neisseria. That other . . .
Re: Bayan Alsaid, Thomas Bessede, Djibril Diallo, et al. Division of Autonomic Nerves Within the Neurovascular Bundles Distally into Corpora Cavernosa and Corpus Spongiosum Components: Immunohistochemical Confirmation with Three-Dimensional Reconstruction. Eur Urol 2011;59:902–9
Authors: Declan G. Murphy, Thomas J. Walton, Paul J. Cathcart, Stephen S. Connolly, Anthony J. Costello
Journal: European Urology (2011)
Highs and Lows in Lipoprotein Cholesterol
Authors: Samuel Vaisrub
Journal: JAMA (1977)

Hypercholesterolemia has long loomed large amidst the various risk factors for coronary disease. A vast amount of effort and expense has gone into the study of its cause, mechanism, epidemiology, and possible correction by diet and drugs. Even now, despite recent doubts, the plasma cholesterol level is believed by many to be a reliable atherogenic index. With increasing understanding of the metabolism and transport of cholesterol, this simplistic index gave way to a sophisticated schema in which the low-density β-lipoprotein cholesterol level, rather than the total plasma cholesterol level became a key to atherogenesis. However, the lipoprotein story did not end there. A new contender, high-density α-lipoprotein cholesterol, entered the atherogenic arena. A number of investigators recently reexamined the effect of this lipoprotein on atherogenesis—an effect observed by Barr et al<sup>1</sup>in 1951 but ignored since that time. In contrast with the atherogenic β-lipoprotein, the high-density α-lipoprotein appears to
The hemodynamic effects of induced supraventricular tachycardia in man.
Authors: B N Goldreyer, J A Kastor, K L Kershbaum
Journal: Circulation (1976)

The circulatory effects of supraventricular tachycardia (SVT) were studied in eight patients who reported disabling symptoms during paroxysms of the arrhythmia. Supraventricular tachycardia was induced in each patient by rapid atrial pacing or with atrial premature stimuli. Hemodynamic parameters in sinus rhythm and following the initiation of SVT were recorded and compared. The following mean values were observed in sinus rhythm (SR) and SVT. Heart rate (beats/min): SR 79, SVT 183; P-R interval (msec): during SR, 154; during SVT, 256; ratio of mean P-R intervals to mean R-R cycl lengths: SR 20%, SVT 76%; brachial artery pressures (mmHg): SR 141, SVT 99; cardiac index (L/min/m2): SR 3.6, SVT 2.2; pulmonary artery pressures (mmHg): SR 18/7, SVT 26/15; peak right atrial pressures (mm Hg): SR 4, SVT 17. Large waves appeared in the right atrium during SVT due to atrial contraction against closed tricuspid valves. Pulsus alternans were observed in each case during SVT. Despite the presence of chest pain during SVT, the coronary arteries were normally patent in four patients who underwent coronary arteriography.
Is Microanatomy Destiny?
Authors: Julie R. Ingelfinger
Journal: New England Journal of Medicine (2003)

Dissecting the pathogenesis of primary, or “essential,” hypertension has proved elusive. In recent years, the hypothesis that having relatively fewer nephrons renders an otherwise healthy person more susceptible to renal disease, hypertension, or both has been supported by a substantive body of experimental data. However, data in humans have been largely circumstantial and indirect.In this issue of the Journal, Keller et al. (pages 101–108) present carefully derived evidence that bolsters this hypothesis. Kidneys from 10 persons who had died in accidents and who had had hypertension were compared with kidneys from 10 age-matched persons with normal blood pressure who . . .