tbuckley/cabot-search huggingface dataset:
Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis
Authors: Dominic J. Ciavatta, JiaJin Yang, Gloria A. Preston, Anshul K. Badhwar, Hong Xiao, Peter Hewins, Carla M. Nester, William F. Pendergraft, Terry R. Magnuson, J. Charles Jennette, Ronald J. Falk
Journal: Journal of Clinical Investigation (2010)

Antineutrophil cytoplasmic autoantibody (ANCA) causes vascular injury that leads to small-vessel vasculitis. Patients with ANCA aberrantly express neutrophil granule-encoding genes, including 2 that encode autoantigens: proteinase 3 (PR3) and myeloperoxidase (MPO). To uncover a potential transcriptional regulatory mechanism for PR3 and MPO disrupted in patients with ANCA vasculitis, we examined the PR3 and MPO loci in neutrophils from ANCA patients and healthy control individuals for epigenetic modifications associated with gene silencing. We found that levels of the chromatin modification H3K27me3, which is associated with gene silencing, were depleted at PR3 and MPO loci in ANCA patients compared with healthy controls. Interestingly, in both patients and controls, DNA was unmethylated at a CpG island in PR3, whereas in healthy controls, DNA was methylated at a CpG island in MPO. Consistent with decreased levels of H3K27me3, JMJD3, the demethylase specific for H3K27me3, was preferentially expressed in ANCA patients versus healthy controls. In addition, we describe a mechanism for recruiting the H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) to PR3 and MPO loci mediated by RUNX3. RUNX3 message was decreased in patients compared with healthy controls, and may also be under epigenetic control. DNA methylation was increased at the RUNX3 promoter in ANCA patients. These data indicate that epigenetic modifications associated with gene silencing are perturbed at ANCA autoantigen-encoding genes, potentially contributing to inappropriate expression of PR3 and MPO in ANCA patients.
Current Concepts in Dyslexia
Authors: Marjorie C. Meehan
Journal: JAMA (1972)

Children with Learning Disabilities: A Five-Year Follow-up Study, by Elizabeth Munsterberg Koppitz, 218 pp, with illus, $9.75, New York: Grune & Stratton, Inc., 1971.  Progress in Learning Disabilities, vol 2, edited by Helmer R. Myklebust, 404 pp, with illus, $13.75, New York: Grune & Stratton, Inc., 1971.  Dyslexia, learning disability, minimal brain dysfunction, hyperkinetic syndrome, emotional disturbance, perceptual handicap, and brain injury are some of the diagnoses applied to children who, despite approximately normal intelligence, have great difficulty learning and behaving appropriately in school. These youngsters, formerly considered lazy, stupid, or bad, have recently been recognized as handicapped. In the past few years, workers in many fields have been investigating their problems, trying, without much success, to discover the causes and cure. Nearly everyone agrees that the major burden of treatment falls on educators, but also involved are physicians, especially pediatricians, ophthalmologists, neurologists, and psychiatrists, as well as psychologists, speech
Differential carcinogenic effects of intraperitoneal initiation with 7,12-dimethylbenz(a)anthracene or urethane and topical promotion with 12-O-tetradecanoylphorbol-13-acetate in skin and internal tissues of female SENCAR and BALB/c mice.
Authors: J M Ward, S Rehm, D Devor, H Hennings, M L Wenk
Journal: Environmental Health Perspectives (1986)

Groups of female SENCAR or BALB/c mice were initiated once intraperitoneally with 300 micrograms/mouse of 7,12-dimethylbenz(a)anthracene (DMBA) or 20 mg/mouse of urethane at 7 weeks of age. Beginning one week later, mice received topically applied acetone or 12-O-tetradecanoylphorbol-13-acetate (TPA), once weekly, at 2.5 micrograms/mouse for weeks 1 through 6 and 1.25 micrograms/mouse for weeks 7 through 52. The skin lesions were evaluated clinically. A complete necropsy was performed on all mice at week 52. SENCAR mice exposed to DMBA/TPA and urethane/TPA had more skin tumors than SENCAR mice exposed to DMBA or urethane alone and more than BALB/c mice in any treatment group. Of all skin carcinomas diagnosed histologically in DMBA/TPA-exposed mice, less than one-third had been identified clinically while the mice were alive. Most of the carcinomas arose within papillomas. BALB/c mice developed more vascular and uterine tumors than did SENCAR mice injected with DMBA and more lung and vascular tumors than did SENCAR mice injected with urethane. TPA exposure after treatment with either initiator had no significant effect on internal tumor development in either SENCAR or BALB/c mice.
Heparin inhibits mesenteric vascular hypertrophy in angiotensin II-infusion hypertension in rats
Authors: R Dilley
Journal: Cardiovascular Research (1998)

Objective: Chronic infusion with angiotensin II increases blood pressure and activates growth mechanisms to produce hypertrophy of the heart and vessels. In order to better understand mechanisms of angiotensin II induced vascular hypertrophy, this study aimed to determine whether heparin, a potent inhibitor of smooth muscle proliferation mechanisms, was able to inhibit vascular hypertrophy. Methods: Angiotensin II (100, 200 or 300 ng/min/kg s.c.) or a saline vehicle control were infused into rats for 14 days. A separate group of animals were co-infused with heparin (0.3 mg/h/kg i.v.) and angiotensin II (200 ng/min/kg s.c.) to test whether hypertension or hypertrophy were antagonized. Blood pressure was measured by tail cuff method and vessel media cross sectional area was measured by morphometry in aorta and mesenteric arteries. Results: Blood pressure elevation and cardiovascular hypertrophy produced by angiotensin II were strongly dose-dependent. Hypertrophy responses at 14 days of treatment also appeared to be influenced partly by local factors as medial cross sectional area was increased more in mesenteric arteries than in thoracic aorta, and left ventricle weight was least affected. Heparin treatment did not influence the increase of blood pressure in angiotensin II infused animals, but the mesenteric vascular hypertrophy response due to angiotensin II was inhibited by approximately 50%. Inhibition of a modest cardiac hypertrophy and aortic medial hypertrophy did not reach significance. Conclusions: Angiotensin II infusion produced vascular medial hypertrophy and increased blood pressure, however the inhibitory effect of heparin on hypertrophy in mesenteric arteries was not mediated through angiotensin II induced vasoconstriction or blood pressure elevation. These data suggest that heparin interferes directly with the hypertrophy mechanism in mesenteric arteries, and that heparin-sensitive growth mechanisms are important in mediating angiotensin induced mesenteric vascular hypertrophy.
C1r, subunit of the first complement component: purification, properties, and assay based on its linking role
Authors: Maria M. E. De Bracco, R. M. Stroud
Journal: Journal of Clinical Investigation (1971)

A method to obtain C1r, a subunit of the first complement component, in a highly purified state has been described for the first time. The stepwise method starts with a neutral euglobulin precipitation, after diethylaminoethyl- and carboxymethyl-cellulose chromatography and a final preparative polyacrylamide electrophoresis step. Such C1r preparations are devoid of C1q and C1s activities and show only one protein band on analytic polyacrylamide electrophoresis. Rabbits injected with this preparation produced antisera showing only one precipitation band. The stability of C1r activity was determined under different conditions, and C1r was found to be labile at 37 degrees C, pH 7-8 and low ionic strength. The electrophoretic mobility of purified C1r is that of a beta-globulin on disc acrylamide electrophoresis and on agarose electrophoresis at pH 8.6. Its molecular weight as estimated by sephadex chromatography is 168,100.A sensitive hemolytic assay based on the property of C1r to link C1s to C1q and thereby to generate macromolecular C[unk]1 is described. The number of C[unk]1 molecules generated is stoichiometrically related to the concentration of C1r for a fixed C1q and C1s concentration provided that the titration is carried out below the plateau zone. Macromolecular C1 can be separated from free C1s as the former is cell bound. This method of purification and assay should allow the development of monospecific antisera and further chemical study of C1r.
Endogenous estrogens and breast cancer risk: the case for prospective cohort studies.
Authors: P G Toniolo
Journal: Environmental Health Perspectives (1997)

It is generally agreed that estrogens, and possibly androgens, are important in the etiology of breast cancer, but no consensus exists as to the precise estrogenic or androgenic environment that characterizes risk, or the exogenous factors that influence the hormonal milieu. Nearly all the epidemiological studies conducted in the 1970s and 1980s were hospital-based case-control studies in which specimen sampling was performed well after the clinical appearance of the disease. Early prospective cohort studies also had limitations in their small sample sizes or short follow-up periods. However, more recent case-control studies nested within large cohorts, such as the New York University Women's Health Study and the Ormoni e Dieta nell'Eziologia dei Tumori study in Italy, are generating new data indicating that increased levels of estrone, estradiol and bioavailable estradiol, as well as their androgenic precursors, may be associated with a 4- to 6-fold increase in the risk of postmenopausal breast cancer. Further new evidence, which complements and expands the observations from the latter studies, shows that women with the thickest bone density, which may be a surrogate for cumulated exposure to hormones, experience severalfold increased risk of subsequent breast cancer as compared to women with thin bones. These data suggests that endogenous sex hormones are a key factor in the etiology of postmenopausal breast cancer. New prospective cohort studies should be conducted to examine the role of endogenous sex hormones in blood and urine samples obtained early in the natural history of breast cancer jointly with an assessment of bone density and of other important risk factors, such as mammographic density, physical activity, body weight, and markers of individual susceptibility, which may confer increased risk through an effect on the metabolism of endogenous hormones or through specific metabolic responses to Western lifestyle and diet.
The Sanitation of Houses, Especially in the Matter of Drainage
Authors: W. Eassie
Journal: BMJ (1875)

larged thyroid gland in this body, that it might w.'ith a possible advan- tage have been remioved by oper-ation.Although this would have been practicable in this inlstance, still in others the tumour may be so situated, and may have formiie(d such adhesions, as to preclude any attempt at extirpation.The respiration and swvallowing may be both much im- pairecl, alndl every relmiedly may have been tried an(d failed.Undersuch circumstances, is it necessary to leave the lpatient to die a miserable and lingering deatlh?or is there any expedient wvhich may reasonably be employedl to p-otract life, anid to rencler existence more comfort- able?Such ain expedlienit is witlhin our reach.The dissection of this case proves its p)racticability.Tfhere it lhas been menitionied that the upper thyr-oid artery was greatly enlarged ; that it was even nearly equal in size to the carotid ; and also that it lay very near to the sur- face.Its coverin-s wvere fewi, and thiln; the pulsations of the artery were strong an(l distinct.Ilaced as that vessel almost always is, no one wouild lhave experienced (lifficulty in reaching it.''lhe lpulsation itself would be a guide, xxlhich would conduct us easily and safely to the vessel.iNo uierve of amy importance wvould come in the way; no muscle xvould ieq iile to be (lisplace(I ; nio deptlh of stubstanice to be diviled ; nio intricate dissection to be perfor-me(l.A small incision w%vould expose that vessel on which the tumour in great measure depenlded for its support.It would be easy to carry a ligature round it to intercept the floxv of bloo(d to the glani(d; anid, till the other vessels
Autoantibodies predicting the outcome of rheumatoid arthritis: evaluation in two subsets of patients according to severity of radiographic damage
Authors: O Meyer, B Combe, A Elias, K Benali, J Clot, J Sany, J F Eliaou
Journal: Annals of the Rheumatic Diseases (1997)

Autoantibodies such as rheumatoid factor (RF), antikeratin antibodies (AKA), antiperinuclear factor (APF), and anti-RA 33 antibodies are considered of value for the diagnosis of RA. The purpose of this study was to evaluate these autoantibodies as predictors of severe radiographic damage in rheumatoid arthritis (RA).Eighty six patients with RA (70 women, 16 men) fulfilling 1987 ACR criteria were selected from a cohort of 469 patients followed up since the first year of RA onset because they could be divided in two groups according to the severity of the radiographic damage. These 86 patients had a mean (SD) disease duration of eight (four) years: 43 patients had severe radiographic damage (Larsen score > or = 2) and 43 had limited radiographic damage (Larsen score < 2). The two groups were matched by disease duration and sex. The following autoantibodies were looked for: RF, ANA, AKA, APF, and anti-RA 33 antibodies. In addition, HLA class II DR beta alleles and standard inflammatory parameters (erythrocyte sedimentation rate, C reactive protein) were determined.Patients with severe radiographic damage differed from those with limited radiographic damage in that they had higher RF (p = 0.01), APF (p < 0.02), and AKA (p = 0.001) titres. Stepwise regression analysis was done to calculate the odds ratios (OR) for each clinical and laboratory variable; only presence of cutaneous nodules (OR: 14.9; 95% CI: 7, 128), HLA DRB1*04 or DRB1*01 (OR: 7.53; 95% CI: 1.32, 42.9), AKA (OR: 3.11; 95%, CI: 0.58, 16.8), a high erythrocyte sedimentation rate (OR: 2.66; 95% CI: 0.60, 11.9), and a high C reactive protein value (OR: 7.4; 95% CI: 1.43, 38.1) were predictive of severe radiographic damage.These data suggest that the risk of severe radiographic damage in RA patients is higher when cutaneous nodules, HLA DRB1*04 or DRB1*01, and/or AKA are present. The other autoantibodies of diagnostic significance are of little help for predicting joint destruction.
Clinical Computing in a Teaching Hospital
Authors: Howard L. Bleich, Robert F. Beckley, Gary L. Horowitz, Jerome D. Jackson, Edna S. Moody, Caryn Franklin, Sandra R. Goodman, Michael W. McKay, Richard A. Pope, Timothy Walden, Saul M. Bloom, Warner V. Slack
Journal: New England Journal of Medicine (1985)

This report describes a hospital-wide clinical computing system that permits physicians, nurses, medical students, and other health workers to retrieve data from the clinical laboratories; to look up reports from the departments of radiology and pathology; to look up demographic data and outpatient visits; to look up prescriptions filled in the outpatient pharmacy; to perform bibliographic retrieval of the MEDLINE data base; to read, write, retract, edit, and forward electronic mail; and to request delivery of a patient's chart. During a one-week study period, from 300 video display terminals located throughout the hospital, 818 patient care providers used a common registry of 539,000 patients to look up clinical and laboratory data 16,768 times; 477 other hospital workers used the patient registry 46,579 times. In a separate study of 586 health care providers, 470 (80 per cent) indicated that they used computer terminals "most of the time" to look up laboratory results; in contrast, 48 (8 per cent) preferred printed reports. Of 545 hospital workers, 440 (81 per cent) indicated that the computer terminals definitely or probably made their work more accurate, and 452 (83 per cent) indicated that terminals enabled them to work faster. The large amount of use by clinicians and their judgment that the computer has been so helpful to them suggests that a reliable, comprehensive, and easy-to-use computer system can contribute substantially to the quality of patient care.
Erythromycin Ethylsuccinate Hepatotoxicity
Authors: David Sullivan
Journal: JAMA (1980)

ERYTHROMYCIN is available to the clinician in several forms, each of which differs primarily because of a single substitution at the two-prime position of the desoamine moiety. All commonly available forms can be associated with mild abdominal cramping, nausea and vomiting, diarrhea, and hypersensitivity reactions. Hepatotoxicity presenting dramatically with fever and abdominal pain suggesting an acute surgical abdomen has been associated only with the estolate form of the antibiotic. The following case illustrates a similar syndrome related to the ethylsuccinate preparations.<sup>1</sup> <h3>Report of a Case</h3> A 45-year-old woman was given erythromycin ethylsuccinate (EES-400), 400 mg orally four times daily, after two weeks of rhinitis and productive cough. On the ninth day of therapy, the patient had sudden onset of severe right upper quadrant pain, fever (temperature, 40 °C), shaking chills, nausea, and vomiting. Erythromycin administration was discontinued. As the acute symptoms lessened over the next 24 hours, dark urine
AN ANAEROBIC ORGANISM ASSOCIATED WITH ACUTE RHINITIS
Authors: RUTH TUNNICLIFF
Journal: JAMA (1913)

Many efforts have been made to determine the cause of acute rhinitis, but so far as I am able to learn all the investigations have been made with aerobic methods. The organism now described has been found during the early stages of acute coryza, while the discharge is mucoid in character. At this time few, often no other, bacteria are present in the smears. The organism is often found in large numbers. As the mucus disappears or the discharge becomes purulent, it decreases in number and finally disappears. It has been observed in all of the cases of acute rhinitis studied. Eighteen different persons have been examined during the acute attack, one during each of four attacks and another during each of five, so that altogether I have made observations during twenty-five distinct attacks. Many examinations were made during the course of the infection in nine of these cases. In
Localized delivery of growth factors for periodontal tissue regeneration: Role, strategies, and perspectives
Authors: Fa‐Ming Chen, Richard M. Shelton, Yan Jin, Iain L.C. Chapple
Journal: Medicinal Research Reviews (2009)

Abstract Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. Localized delivery of growth factors to the periodontium is an emerging and versatile therapeutic approach, with the potential to become a powerful tool in future regenerative periodontal therapy. Optimized delivery regimes and well‐defined release kinetics appear to be logical prerequisites for safe and efficacious clinical application of growth factors and to avoid unwanted side effects and toxicity. While adequate concentrations of growth factor(s) need to be appropriately localized, delivery vehicles are also expected to possess properties such as protein protection, precision in controlled release, biocompatibility and biodegradability, self‐regulated therapeutic activity, potential for multiple delivery, and good cell/tissue penetration. Here, current knowledge, recent advances, and future possibilities of growth factor delivery strategies are outlined for periodontal regeneration. First, the role of those growth factors that have been implicated in the periodontal healing/regeneration process, general requirements for their delivery, and the different material types available are described. A detailed discussion follows of current strategies for the selection of devices for localized growth factor delivery, with particular emphasis placed upon their advantages and disadvantages and future prospects for ongoing studies in reconstructing the tooth supporting apparatus. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 3, 472‐513, 2009
Genetic epidemiology of the susceptibility to leprosy.
Authors: E D Shields, D A Russell, M A Pericak-Vance
Journal: Journal of Clinical Investigation (1987)

To test the hypothesis that genetic factors are operative in the predisposition to leprosy (Hansen's disease) in humans, a genetic epidemiologic investigation was performed on 269 leprosy kindreds containing 552 affected individuals from an isolated population in Papua New Guinea. The community, and not the family, was the basic social unit. Leprosy, an infectious disease, was not communal but strongly familial within the Karimui. Segregation analysis, to determine whether a major gene for the susceptibility to leprosy was segregating within a single multi-generational kindred, could not differentiate between a Mendelian genetic and a purely environmental hypothesis. The composite kindred data, however, suggest a genetic hypothesis for the non-immunologically induced susceptibility to leprosy per se. Within familial kindreds leprosy invariably emanated from a common ancestral sibship, and risk was associated with the closeness of kin but not with infectivity or severity.
Long-lasting effect of oral molsydomine on exercise performance: a new antianginal agent.
Authors: A Takeshita, M Nakamura, T Tajimi, H Matsuguchi, A Kuroiwa
Journal: Circulation (1977)

This study examines whether the beneficial effects of molsydomine, a recently introduced antianginal agent, on exercise performance of patients with angina pectoris are long lasting. The hemodynamic effects are known to persist for several hours. The effects of molsydomine on the duration of exercise and the time to the onset of ST depression were compared to those of placebo during two hours after oral administration. Molsydomine prolonged the duration of exercise in all eight patients (average 2.8 min, P less than 0.001) and delayed the onset of ST depression (average 2.2 min, P less than 0.001), while the placebo failed to alter these measurements. The increment of the duration of exercise produced by 2 mg of molsydomine in two hours following oral administration was comparable to the increment produced in a few minutes after 0.3 mg of nitroglycerin given sublingually. The results indicate that molsydomine offers prophylasis for angina pectoris that lasts at least two hours after oral administration.
<i>In Vivo</i> Treatment with Endotoxin Increases Rat Pulmonary Vascular Contractility Despite NOS Induction
Authors: MARK J. D. GRIFFITHS, NICHOLAS P. CURZEN, JANE A. MITCHELL, TIMOTHY W. EVANS
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Pulmonary hypertension is a feature of clinical and experimental acute lung injury. Nitric oxide (NO) synthesis is increased in hyporesponsive systemic and pulmonary conductance arteries after endotoxin (LPS) injection in the rat. We examined the effects of NO synthase (NOS) induction by LPS on vascular reactivity of the isolated perfused rat lung (IPL) using the selective inducible (iNOS) inhibitor aminoguanidine (AG). Baseline pulmonary artery pressures (Ppa) were higher in the LPS compared with the sham-treated rats and were further increased only in the LPS-treated group by AG. Increased NOS activity in whole lung and the vasopressor effect of AG suggested that iNOS was active in pulmonary resistance vessels after LPS treatment. Vasoconstriction to hypoxia, angiotensin II (AII), and prostaglandin F2 α (PGF2 α) was enhanced or unchanged in LPS-treated rats despite NOS induction. Hence, iNOS activity counterbalances increased pulmonary vascular contractility in this model.