tbuckley/cabot-search huggingface dataset:
Vitaminized Cordials and Teeth
Authors: G. B. Winter
Journal: BMJ (1960)

<b>Background and aims:</b> Although most cases of hereditary haemochromatosis are associated with homozygosity for the C282Y mutation of the HFE gene, clinical penetrance varies and other genes may modify disease expression. If so, relatives from clinically affected families, by inheriting such genes, may accumulate more iron. To seek evidence for this, we compared iron status and morbidity in unselected first degree relatives of two groups of index cases from South Wales, namely asymptomatic C282Y homozygotes identified by genetic screening of blood donors (n = 56) and C282Y homozygous haemochromatosis patients presenting clinically (n = 60). <b>Methods:</b> All participating relatives had a structured interview, clinical assessment, and laboratory investigations. Health related quality of life was measured (SF-36 version 2). <b>Results:</b> In total, 92% of 180 eligible first degree relatives were interviewed in the “screened” family group and 85% of 143 eligible relatives in the “patient” group. Of 59 relatives homozygous for C282Y, 76% of men and 32% of women had the “iron phenotype” (raised transferrin saturation and serum ferritin). Logistic regression modelling of the iron phenotype risk showed that 42% of the initial model deviance could be explained by homozygosity for C282Y, another 6% by lifestyle factors, and 6% by being male. Family group membership was not a significant risk factor. Morbidity and SF-36 scores did not differ significantly either between C282Y homozygotes and relatives lacking C282Y, or between C282Y homozygotes from the “screened” and “patient” groups. Serious morbidity (including cirrhosis) was low in both groups of relatives. <b>Conclusions:</b><i>HFE</i> C282Y homozygosity has a high penetrance for iron accumulation but a low clinical penetrance. Lack of excess morbidity among C282Y homozygous relatives of index cases who presented clinically suggests that residual unknown genetic or environmental factors do not greatly influence clinical outcome among C282Y homozygotes.
Effect of methyl isocyanate (MIC) gas on the eyes of Fischer 344 rats.
Authors: B N Gupta, S A Stefanski, J R Bucher, L B Hall
Journal: Environmental Health Perspectives (1987)

The accidental release of methyl isocyanate gas in Bhopal, India, was reported to cause temporary blindness and other eye injuries in many of the exposed people. Methyl isocyanate (MIC) is known to be corrosive and to irritate intact skin and mucous membranes, but little is known about the extent of ocular damage incurred during exposure to its vapors. The eyes of male and female Fischer 344 rats were evaluated immediately after a 2-hr exposure to 0, 3, 10, or 30 ppm of MIC, and periodically thereafter during a 91-day recovery period. During exposure to 10 ppm and higher concentrations, rats kept their eyes partially closed. Copious lacrimation and occasional frothy nasal discharge were evident. Eyes were examined under ultraviolet light after topical application of sodium fluorescein, and histopathologic examination included lids, cornea, lens, retina, optic nerve, and Harderian gland. There was no significant gross or microscopic evidence of epithelial erosion or ulceration of the cornea, or of adjacent tissues immediately after, or at any time following exposures. No skin irritation was noted. It would appear that the natural protective mechanisms of the eye of rats were adequate to prevent ocular damage at these exposure levels.
Isolation and Optimization of Murine IL-10 Receptor Blocking Oligonucleotide Aptamers Using High-throughput Sequencing
Authors: Alexey Berezhnoy, C. Andrew Stewart, James O. Mcnamara II, William Thiel, Paloma Giangrande, Giorgio Trinchieri, Eli Gilboa
Journal: Molecular Therapy (2012)

Interleukin-10 (IL-10) is a key suppressor of inflammation in chronic infections and in cancer. In mice, the inability of the immune system to clear viral infections or inhibit tumor growth can be reversed by antibody-mediated blockade of IL-10 action. We used a modified selection protocol to isolate RNA-based, nuclease-resistant, aptamers that bind to the murine IL-10 receptor. After 5 rounds of selection high-throughput sequencing (HTS) was used to analyze the library. Using distribution statistics on about 11 million sequences, aptamers were identified which bound to IL-10 receptor in solution with low Kd. After 12 rounds of selection the predominant IL-10 receptor-binding aptamer identified in the earlier rounds remained, whereas other high-affinity aptamers were not detected. Prevalence of certain nucleotide (nt) substitutions in the sequence of a high-affinity aptamer present in round 5 was used to deduce its secondary structure and guide the truncation of the aptamer resulting in a shortened 48-nt long aptamer with increased affinity. The aptamer also bound to IL-10 receptor on the cell surface and blocked IL-10 function in vitro. Systemic administration of the truncated aptamer was capable of inhibiting tumor growth in mice to an extent comparable to that of an anti- IL-10 receptor antibody. Interleukin-10 (IL-10) is a key suppressor of inflammation in chronic infections and in cancer. In mice, the inability of the immune system to clear viral infections or inhibit tumor growth can be reversed by antibody-mediated blockade of IL-10 action. We used a modified selection protocol to isolate RNA-based, nuclease-resistant, aptamers that bind to the murine IL-10 receptor. After 5 rounds of selection high-throughput sequencing (HTS) was used to analyze the library. Using distribution statistics on about 11 million sequences, aptamers were identified which bound to IL-10 receptor in solution with low Kd. After 12 rounds of selection the predominant IL-10 receptor-binding aptamer identified in the earlier rounds remained, whereas other high-affinity aptamers were not detected. Prevalence of certain nucleotide (nt) substitutions in the sequence of a high-affinity aptamer present in round 5 was used to deduce its secondary structure and guide the truncation of the aptamer resulting in a shortened 48-nt long aptamer with increased affinity. The aptamer also bound to IL-10 receptor on the cell surface and blocked IL-10 function in vitro. Systemic administration of the truncated aptamer was capable of inhibiting tumor growth in mice to an extent comparable to that of an anti- IL-10 receptor antibody.
Prolonged activated partial thromboplastin time of unknown etiology: A prospective study of 100 consecutive cases referred for consultation
Authors: Craig S. Kitchens
Journal: American Journal of Hematology (1988)

Abstract The activated partial thromboplastin time (aPTT) is frequently used to assess overall competency of the intrinsic pathway of coagulation. An abnormal value may be caused by any of several abnormalities along this pathway or by many other variables including the presence of inhibitors, poor collection of the sample, or variables in the laboratory. When the cause for the prolongation is unknown to the requesting physician, the hematologist may be consulted. In this prospective study, the cause and perceived hemostatic risk to 100 consecutive patients referred to us for consultation regarding a prolonged aPTT of previous unknown cause were evaluated. We found that these abnormal aPTTs may be either indicative of a hemostatic defect, in 50% of the cases, or of no particular risk, in 36% of the cases. In 14%, the aPTT was artifactually prolonged. Most (81%) patients with a prolonged aPTT due to a hemostatic defect had an abnormal hemostatic history but some (19%) did not. Even among true abnormal tests, the degree of abnormality indicated little or nothing about hemostatic competency. We conclude that the cause of an abnormal aPTT is more important than the result itself. These data may be of use to those who consult on such matters.
A Unique Serum Electrophoretic Pattern in Hepatitis.
Authors: Albert Klainer
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970A Unique Serum Electrophoretic Pattern in Hepatitis.Albert Klainer, M.D., (Associate), Samuel Murphy, Ph.D., Tushar Maitra, M.D.Albert Klainer, M.D., (Associate)Search for more papers by this author, Samuel Murphy, Ph.D.Search for more papers by this author, Tushar Maitra, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-793_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe present presumptive diagnosis of viral hepatitis is based on epidemiologic, clinical, and nonspecific laboratory data; in most cases it can be substantiated by liver biopsy. Detection of Australian antigen may possibly provide a better means for both specific diagnosis and identification of the hepatitis carrier but presently lacks sensitivity. This report presents preliminary observations of serum protein and glycoprotein alterations which may be helpful in the detection of viral hepatitis and the hepatitis carrier. Serum fractions obtained by gel chromatography on Sephadex G-200 were further separated by zone electrophoresis on cellulose acetate. Identical strips were stained for protein and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Columbus, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 793-793KeywordsChromatographyClinical epidemiologyClinical laboratoriesGlycoproteinsHepatitisHepatitis ALiverProteinsResearch laboratoriesSerum proteins Issue Published: 1 May 1970 PDF DownloadLoading ...
Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine
Authors: S.P. Raychaudhuri, W-Y. Jiang, E.M. Farber
Journal: British Journal of Dermatology (2001)

Chemokines play a key role in cell trafficking at sites of inflammation. The fractalkine CX3C chemokine is unique in several aspects. Fractalkine is expressed on activated endothelial cells and exists in two forms, either membrane anchored or in a soluble form. The soluble form is a potent chemotactic agent for T cells/monocytes and the anchored form functions as an adhesion molecule. In view of these specific functions fractalkine is capable of controlling the key regulatory mechanisms of cell trafficking at sites of inflammation.Little is known about the significance of this important molecule in inflammatory diseases. We undertook this study to elucidate the role of fractalkine in inflammatory diseases of the skin.We used a polyclonal antifractalkine antibody (immunoperoxidase and immunofluorescence stainings) in cryosections obtained from tissues of normal skin and that of selected cutaneous inflammatory diseases (psoriasis, lichen planus, eczema).Increased expression of fractalkine was observed in the dermal blood vessels of lichen planus, eczema and psoriasis tissues. The most striking finding was that the dermal dendrocytes in the papillary dermis of psoriasis tissues expressed high levels of fractalkine. Compared with 186.64 +/- 51.69 fractalkine positive dermal dendrocytes per mm2 of the upper dermis of psoriatic tissue, the number of positive cells in lichen planus, eczema, and normal skin were 17.29 +/- 12.50, 12.50 +/- 6.75 and 5.93 +/- 3.53, respectively. We also performed double label immunofluorescence staining with nerve growth factor receptor (NGF-R) antibody and fractalkine antibody. NGF-R-positive terminal cutaneous nerves were in close contact with the fractalkine-positive dermal dendrocytes in psoriatic lesions.The results of this study confirm that fractalkine is upregulated at sites of inflammation. Thus, it is likely that this molecule plays a key part in cell trafficking. An increased expression of fractalkine at the dermal papillae provides a plausible explanation for the migration and accumulation of T cells at these sites in psoriasis. Earlier studies have reported an increased number of dermal dendrocytes in psoriatic tissue; however, the functional role of these cells in the pathogenesis of psoriasis is largely unknown. Expression of fractalkine on the surface of dermal dendrocytes suggests an active role for these cells in localization and activation of lesional T cells.
Systematic Review: Association of Low-Density Lipoprotein Subfractions With Cardiovascular Outcomes
Authors: Stanley Ip
Journal: Annals of Internal Medicine (2009)

Background: Measures of low-density lipoprotein (LDL) subfractions have been proposed as an independent risk factor for cardiovascular disease. Purpose: To review published studies that reported relationships between LDL subfractions and cardiovascular outcomes. Data Sources: MEDLINE (1950 to 5 January 2009), CAB Abstracts (1973 to 30 June 2008), and Cochrane Central Register of Controlled Trials (2nd quarter of 2008), limited to English-language studies. Study Selection: 3 reviewers selected longitudinal studies with 10 or more participants that reported an association between LDL subfractions and incidence or severity of cardiovascular disease and in which plasma samples were collected before outcome determination. Data Extraction: Data were extracted from 24 studies. The 10 studies that used analytical methods available for clinical use (all of which used nuclear magnetic resonance) had full data extraction, including quality assessment (good, fair, or poor). All studies were extracted by 1 researcher and verified by another. Data Synthesis: All 24 studies, and the subset of 10 nuclear magnetic resonance studies, were heterogeneous in terms of the specific tests analyzed, analytical methods used, participants investigated, and outcomes measured. Higher LDL particle number was consistently associated with increased risk for cardiovascular disease, independent of other lipid measurements. Other LDL subfractions were generally not associated with cardiovascular disease after adjustment for cholesterol concentrations. No study evaluated the incremental value of LDL subfractions beyond traditional cardiovascular risk factors or their test performance. Limitation: Publication bias was a possibility. Conclusion: Higher LDL particle number has been associated with cardiovascular disease incidence, but studies have not determined whether any measures of LDL subfractions add incremental benefit to traditional risk factor assessment. Routine use of clinically available LDL subfraction tests to estimate cardiovascular disease risk is premature.
The Ethiopian Cereal Tef in Celiac Disease
Authors: Liesbeth Spaenij-Dekking, Yvonne Kooy-Winkelaar, Frits Koning
Journal: New England Journal of Medicine (2005)

To the Editor: Celiac disease is caused by aberrant T-cell responses to wheat gluten and the gluten-like proteins in barley and rye.1 The only cure for the disease is a lifelong gluten-free diet. A...
The immuno-neuroendocrine interface
Authors: Shlomo Melmed
Journal: Journal of Clinical Investigation (2001)

J. Clin. Invest. 108:1563–1566 (2001). DOI:10.1172/JCI200114604.

During the final production stage of this manuscript, Figure 1 was mislabeled. The corrected figure and the accompanying legend appear below. We regret the error and have provided the author with corrected reprints.

Figure 1





Model for regulation of anterior pituitary hormone secretion by three tiers of control. Hypothalamic hormones traverse the portal system and impinge directly upon their respective target cells. Intrapituitary cytokines and growth factors regulate tropic cell function by paracrine (and autocrine) control. Peripheral hormones exert negative feedback inhibition of respective pituitary trophic hormone synthesis and secretion. Reproduced with permission from Endocrine Reviews (2).



Additionally, CRH was mislabeled in Figure 2. The correct version of the figure and the accompanying legend appear below.

Figure 2





Mechanisms regulating the rhythmicity of the HPA axis. The acute stress response of ACTH secretion is reflected by enhanced pulse amplitude that declines rapidly. Adapted from ref. 28.
A mycolic acid–specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection
Authors: Damien J. Montamat-Sicotte, Kerry A. Millington, Carrie R. Willcox, Suzie Hingley-Wilson, Sarah Hackforth, John Innes, Onn Min Kon, David A. Lammas, David E. Minnikin, Gurdyal S. Besra, Benjamin E. Willcox, Ajit Lalvani
Journal: Journal of Clinical Investigation (2011)

Current tuberculosis (TB) vaccine strategies are largely aimed at activating conventional T cell responses to mycobacterial protein antigens. However, the lipid-rich cell wall of Mycobacterium tuberculosis (M. tuberculosis) is essential for pathogenicity and provides targets for unconventional T cell recognition. Group 1 CD1–restricted T cells recognize mycobacterial lipids, but their function in human TB is unclear and their ability to establish memory is unknown. Here, we characterized T cells specific for mycolic acid (MA), the predominant mycobacterial cell wall lipid and key virulence factor, in patients with active TB infection. MA-specific T cells were predominant in TB patients at diagnosis, but were absent in uninfected bacillus Calmette-Guérin–vaccinated (BCG-vaccinated) controls. These T cells were CD1b restricted, detectable in blood and disease sites, produced both IFN-γ and IL-2, and exhibited effector and central memory phenotypes. MA-specific responses contracted markedly with declining pathogen burden and, in patients followed longitudinally, exhibited recall expansion upon antigen reencounter in vitro long after successful treatment, indicative of lipid-specific immunological memory. T cell recognition of MA is therefore a significant component of the acute adaptive and memory immune response in TB, suggesting that mycobacterial lipids may be promising targets for improved TB vaccines.
Rectal diclofenac compared with pethidine injection in acute renal colic.
Authors: J. F. Thompson, J. M. Pike, P. D. Chumas, J. S. Rundle
Journal: BMJ (1989)

numbers of patients of the same age and socioeconomic distribution.Each has similar gastroenterological interests, has identical on call commitments for emergencies, and has been in post for about 10 years.This prospective study was carried out over 18 months from July 1986 to December 1987, when all the elective admissions and cancellations were recorded and the reasons for non-attendance sought.Statistical analysis was by the X2 test and a comparison of means.The table gives the results.There were 113 fewer cancellations with the booking system than with the waiting list system (X2=5l1 p<0O001).The mean time to admission was also significantly shorter with the booking system (5 1 (SD 9-5) weeks, range 1 day-130 weeks) than with the waiting list (11-4 (12 2) weeks, range 1 day-96 weeks; p<O 001).The average notice of admission given to patients on the waiting lists was one week.
Die humorale Steuerung der Erythropoiese
Authors: Leon O. Jacobson
Journal: JAMA (1964)

The field of research relating to erythropoiesis has recently so expanded that the yearly appearance of a new volume recapitulating and updating our information has ceased to cause surprise. The task is here very ably performed. The present volume, after an introduction by one of the pioneers in the field, Professor Ferdinand Hoff, discusses nervous and humoral regulation of erythropoiesis, specific humoral control of erythropoiesis by erythropoietin, and nonspecific humoral influences on erythropoiesis. There is a very extensive bibliography. It is necessary to distinguish between two aspects of the work, the author's own contributions (some of them published here for the first time) and his review of the literature. The author's own contributions range over a wide field and include studies on such subjects as the nature of cells responding to injections of erythropoietin; the effect of anemic plasma filtrates on oxygen consumption in the chick erythrocyte; the effects of
Hormones of the Anterior Pituitary Body
Authors: Henry Friesen, E. B. Astwood
Journal: New England Journal of Medicine (1965)

THE elucidation of the major functions of the anterior lobe of the pituitary gland during the past four decades is a monument of scientific achievement. In a microcosmic sense its history parallels and reflects the developments of biologic investigation during this period. Initially, a series of discoveries that ultimately led to the definition of the active principles involved revealed that the gland exercises direct or indirect control over a wide spectrum of biologic processes. The earlier difficulties encountered in the isolation and purification of individual hormones now seem nearer to solution with the development of superior analytical and preparative methods. . . .
BLOCKING LYMPHATICS IN THE CONTROL OF CARCINOMA OF THE PROSTATE GLAND
Authors: ROBERT H. HERBST
Journal: JAMA (1924)

We do not know any more about the cause of cancer of the prostate than we do about cancer occurring in other organs. We do know, however, that at least 20 per cent, of all neoplasms of this gland are malignant. Previous to 1908, little attention was given to the treatment of carcinoma of the prostate. A review of the literature reveals a number of papers bearing on methods of partial or complete excision of the bladder neck for cancer, all carrying with them a high immediate mortality and little success in control of the cancer. The employment of radium in irradiation of carcinoma of the prostate is comparatively recent. Minet,<sup>1</sup>in 1908, using the urethral route, irradiated the surface of the prostate by means of an elbow catheter with the beak hollowed out to receive the radium tube. From this time until 1915, we find a number of
The Blood Flow and Oxygen Consumption of the Brain in Patients with Essential Hypertension before and after Adrenalectomy1
Authors: Joseph H. Hafkenschiel, Carl K. Friedland, Harold A. Zintel
Journal: Journal of Clinical Investigation (1954)

It has been shown that cerebral oxygen consump- tion and blood flow are normal and cerebral vascu- lar resistance is increased in patients with essential hypertension (1).Clinicians have questioned the advisability of lowering arterial pressures in hy- pertensive patients because of the possible un- toward effects consequent to decreased cerebral blood flow (2, 3).We have studied the effect of hypotension, induced by various means, on the oxygen consumption and blood flow of the brain.During the hypotension obtained one hour after the injection of dihydroergocornine (4), proto- veratrine (5), hexamethonium (6), and 1-hydra- zinophthalazine (7), cerebral blood flow and oxygen uptake were unchanged.Cerebral oxy- gen uptake was unchanged and cerebral vascular resistance was decreased during the hypotension induced by differential spinal sympathetic block (8).After thoracolumbar sympathectomy, cere- bral blood flow and oxygen uptake remained con- stant and the cerebral vascular resistance was re- duced toward normal values three weeks to six months after operation (9).Thus, in most of these instances, cerebral blood flow was not re- duced and cerebral oxygen consumption remained unchanged when the arterial pressure was lowered either by the drugs tested or by surgical sympa- thectomy.These hemodynamic observations sug- gested that the cerebral circulation remains ade- quate when the blood pressure is lowered.The increased cerebral vascular resistance in hyper- tension apparently can be reduced by certain meas- ures without reducing cerebral oxygen consump- tion and cerebral blood flow.