tbuckley/cabot-search huggingface dataset:
Transgenic simulation of human heart failure-like L-type Ca2+-channels: implications for fibrosis and heart rate in mice
Authors: Nadine Beetz, Lutz Hein, Janos Meszaros, Ralf Gilsbach, Frederico Barreto, Marcel Meissner, Uta C. Hoppe, Arnold Schwartz, Stefan Herzig, Jan Matthes
Journal: Cardiovascular Research (2009)

AimsCardiac L-type Ca2+-currents show distinct alterations in chronic heart failure, including increased single-channel activity and blunted adrenergic stimulation, but minor changes of whole-cell currents. Expression of L-type Ca2+-channel β2-subunits is enhanced in human failing hearts. In order to determine whether prolonged alteration of Ca2+-channel gating by β2-subunits contributes to heart failure pathogenesis, we generated and characterized transgenic mice with cardiac overexpression of a β2a-subunit or the pore Cav1.2 or both, respectively.
ORGANIC BRAIN SYNDROMES IN A GENERAL HOSPITAL
Authors: GEORGES R. REDING, ROBERT S. DANIELS
Journal: American Journal of Psychiatry (1964)

It is our impression that one of the fundamental reasons for the lack of early recognition of organic brain syndromes lies in the general trend of American psychiatric education during the past 3 decades. Proper emphasis on the psychological and emotional aspects of psychiatric disease has been accompanied by a certain neglect of its organic aspects. Thorough and repeated mental status examinations, continued attention to behavior and personality changes and to nurses' and relatives' reports will result in early diagnosis and possibly more competent handling of cases of organic brain disease.
Violence between intimate partners: working with the whole family
Authors: K. Hegarty, A. Taft, G. Feder
Journal: BMJ (2008)

Violence between intimate partners (one area of domestic violence) is a common violation of human rights, with long term consequences for the health of survivors and their children.1 2 Health services have lagged behind other agencies in responding appropriately to this problem. Here we review the evidence on identification and management of intimate partner violence in families and summarise primary care guideline recommendations from an international consensus group that we led.3

We searched Medline, Embase, CINAHL, PsycINFO, DARE, and Cochrane for recent (1999-2005) clinical guidelines or recommendations about the management of survivors or perpetrators of intimate partner violence and their children, including guidance on care of the whole family. We referred to reviews in Clinical Evidence and systematically reviewed primary studies of advocacy and psychological interventions for survivors.4 We are the key authors on the systematic reviews and consensus guidelines that this review draws on.

Intimate partner violence is defined as any behaviour within an intimate relationship that causes physical, psychological, or sexual harm. This includes:

Lifetime prevalence of isolated violent acts within relationships, is comparable for men and women, but repeated coercive, sexual, or severe physical violence is perpetrated largely against women by men.6 Although intimate partner violence also occurs in same sex relationships, research evidence on the health consequences of intimate partner violence and the management of survivors is largely confined to women in heterosexual relationships, and they are the focus of this review. We do not know to what extent our conclusions can be extrapolated to male patients and to women in …
Evaluation of Left Ventricular Filling Pressures by Doppler Echocardiography in Patients With Hypertrophic Cardiomyopathy
Authors: Jeffrey B. Geske, Paul Sorajja, Rick A. Nishimura, Steve R. Ommen
Journal: Circulation (2007)

Diastolic dysfunction is a major pathophysiological abnormality in hypertrophic cardiomyopathy (HCM). Doppler echocardiographic parameters correlate with left ventricular (LV) filling pressures in other diseases, but it is unclear whether these findings apply to patients with HCM, who have multiple complex interrelated events leading to diastolic dysfunction. This study compares Doppler echocardiographic estimates of filling pressures to direct measurements of left atrial pressure (LAP) via catheterization in 100 patients with HCM.One hundred patients who were symptomatic with HCM (New York Heart Association class III/IV, 82%) underwent measurement of early diastolic transmitral flow velocity (E) and mitral annular velocities (e') with the use of transthoracic echocardiography within 48 hours of cardiac catheterization with direct measurement of LAP. In a subset of 42 patients, echocardiographic and catheterization measurements were performed simultaneously. Mean LAP directly correlated with medial E-e' ratio in the overall population (r=0.44, P<0.0001) and also in the subgroup of patients who had simultaneous echocardiographic and catheterization studies (r=0.28, P=0.07). However, scatter was present. A calculated mean LV filling pressure was derived from the E-e' ratio with the use of a previously described regression equation, and the 95% confidence limits of agreement with measured mean LAP exceeded +/-18 mm Hg both for the overall group and for the subgroup who had simultaneous studies. Similar results were obtained with the lateral E-e' ratio. Only 1 patient had a previously defined "normal" E-e' ratio of <8.In symptomatic patients with HCM, Doppler echocardiographic estimates of LV filling pressure with the use of transmitral flows and mitral annular velocities correlate modestly with direct measurement of LAP. Given the complex nature of diastolic dysfunction in HCM, precise characterization of LV filling pressure in an individual patient cannot be determined with the use of these noninvasive parameters.
Determination of the breakpoints of a chromosomal translocation found in a patient with paroxysmal nocturnal hemoglobinuria
Authors: Norimitsu Inoue, Tomohisa Izui, Maki Kuwayama, Junichi Nishimura, Ken Kurokawa, Takashi Machii, Yuzuru Kanakura, Taroh Kinoshita
Journal: Nature Genetics (2001)
Beryllium Poisoning — Lessons in Control of Man-Made Disease
Authors: Harriet L. Hardy
Journal: New England Journal of Medicine (1965)

THE accidents of my birth date and choice of work have led to the responsibility of honoring my senior colleague, Dr. Alice Hamilton, whose unusual contributions inspired the inauguration of this lectureship. Many in this audience, too young to know just why Dr. Hamilton deserves our praise and thanks, will want a little background.After a rich and varied education here and in Europe, Dr. Hamilton chose to live at Hull House in Chicago, one of the first and greatest settlement houses in this country. Here, people of privilege, under the leadership of Miss Jane Addams, learned of the wretched . . .
Intravenous Immune Globulin in Autoimmune and Inflammatory Diseases
Authors: Erwin W. Gelfand
Journal: New England Journal of Medicine (2012)

The author reviews the many proposed mechanisms by which intravenous immune globulin may exert its antiinflammatory and autoimmunity-inhibiting clinical effects. No single mechanism can explain its activity in diseases with diverse pathophysiological pathways.
Primary thrombocythemia and pregnancy: Treatment and outcome in fifteen cases
Authors: Pasqualepaolo Pagliaro, Luisa Arrigoni, Maria Luisa Muggiasca, Marina Poggio, Umberto Russo, Edoardo Rossi
Journal: American Journal of Hematology (1996)

Pregnancy in patients with primary thrombocythemia (PT) is reported to be often complicated by recurrent abortion and fetal growth retardation. Fifteen pregnancies in nine patients with PT are reported. Nine pregnancies had a good outcome, with the birth of a healthy infant. There were two spontaneous abortions and three intrauterine deaths. One pregnancy was electively terminated after extensive thrombosis in the splanchnic district requiring surgical entero-resection. In five pregnancies the mother received no treatment; in ten pregnancies acetylsalicylic acid (ASA) was prescribed to the mother as soon as she was found pregnant, subcutaneous heparin was added from the middle trimester in seven cases. In patients treated with ASA and subcutaneous heparin pregnancies had a good outcome. Administration of ASA and heparin during pregnancy appears to improve the outcome in patients with PT and can prevent severe maternal complications, but requires close monitoring.
Age-related decrease of calcitonin gene-related peptide-containing vasodilator innervation in the mesenteric resistance vessel of the spontaneously hypertensive rat.
Authors: H Kawasaki, A Saito, K Takasaki
Journal: Circulation Research (1990)

We previously demonstrated that the mesenteric resistance blood vessels have nonadrenergic, noncholinergic vasodilator innervation in which calcitonin gene-related peptide (CGRP) is a possible neurotransmitter. The role of CGRP-containing vasodilator nerves in hypertension was investigated in perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR). The adrenergic vasoconstrictor responses to perivascular nerve stimulation in both SHR (8-, 15-, and 30-week-old) and age-matched Wistar-Kyoto (WKY) rat preparations increased with aging, but the response was greater in SHR than in WKY rats at all ages. The preparation isolated from SHR and WKY rats was precontracted by continuous perfusion of Krebs' solution containing 7 x 10(-6) M methoxamine plus 5 x 10(-6) M guanethidine. In both SHR and WKY rats, perivascular nerve stimulation (1-8 Hz) produced frequency-dependent vasodilation, which was blocked by 1 x 10(-7) M tetrodotoxin, pretreatment with 5 x 10(-7) M capsaicin, and denervation by cold storage (4 degrees C for 72 hours). The vasodilation induced by perivascular nerve stimulation in SHR greatly decreased with age, whereas a slight decrease in the response with age was found in WKY rats. The neurogenic vasodilation in the young SHR preparation was similar in magnitude to the vasodilation in age-matched WKY rats, whereas the vasodilation in 15- and 30-week-old SHR was significantly smaller than that in age-matched WKY rats. In both SHR and WKY rats, perfusion of rat CGRP (1 x 10(-10) to 3 x 10(-8) M) produced marked vasodilation in a concentration-dependent manner. The CGRP-induced vasodilation in SHR increased with age, whereas an age-related decrease in vasodilation was found in WKY rats. Perivascular nerve stimulation (4 and 8 Hz) of the perfused mesenteric vascular bed evoked an increased release of CGRP-like immunoreactive substance in the perfusate, which was significantly less in 15-week-old SHR than in age-matched WKY rats. Immunohistochemical studies showed an age-related decrease in CGRP-like immunoreactive fibers in SHR but not in WKY rats. These results suggest that CGRP-containing vasodilator innervation is greatly decreased when SHR develop and maintain hypertension. It is also suggested that the decreased vasodilator mechanism by CGRP-containing nerves contributes to the development and maintenance of hypertension.
Sarcoidosis in a Clinically Unaffected Joint Demonstrated by Somatostatin Receptor Scintigraphy
Authors: Eric-Jan A. Kroot, R J. E. M. Dolhain, P M. van Hagen, D J. Kwekkeboom
Journal: Clinical Nuclear Medicine (2006)

A patient presented with decreased hearing, secondary amenorrhea, vertigo, dry eyes, and progressive loss of vision. Because the differential diagnosis consisted of sarcoidosis and lymphoma, somatostatin receptor scintigraphy with indium-111-DTPA octreotide (In-111 pentetreotide) was performed. Increased uptake was observed in the parotid gland, bilateral orbits, nose, and the right knee. Remarkably, on clinical examination, no signs of arthritis of the right knee were observed. Additional tissue analysis of the right knee revealed the diagnosis of sarcoidosis leading to successful treatment with prednisolone, antimalarials, and azathioprine. This case underlines the diagnostic potential of somatostatin receptor scintigraphy in patients with sarcoidosis, even in clinically unaffected tissue.
Pedestrian Deaths in Oslo Traffic Accidents
Authors: K. Solheim
Journal: BMJ (1964)

The large towns and cities of the world are endemic foci of pedestrian deaths caused by traffic accidents (Norman, 1962).In Oslo, the capital of Norway (450,000 inhabitants), 25 to 30 persons die from injuries received in traffic injuries every year.This total represents about a twelfth of the yearly toll of traffic victims in the whole country. (Norway has a population of 3,800,000.)In Oslo most of these deaths come to necropsy -usually requested by the Police Department-at Oslo City Hospital and the Rikshospitalet, University of Oslo.From 1952 to 1961 the figure was 88%.My series of 168 fatally injured pedestrians covers this 10-year period.These deaths account for about 65 % of the total number occurring from traffic accidents during the same period in Oslo.In the two five-year periods, 1952-6 and 1957-61, the number of pedestrian deaths decreased from 73% to 58.4% of all deaths from traffic in Oslo, although the total number due to this cause increased by 36%.The increase is explained by the fact that while there was relatively little increase in the size of the population of the city there was a very great increase in the number of cars and motor-cycles.In consequence more deaths from traffic accidents occurred among motorists-in cars and on motor-cycles-in the second five-year period.It must be remembered that the sale of cars in Norway was rigorously restricted during the last war and indeed right up to 1957.In that year their sale again became free.
Effect of Adenovirus Gene Transfer Vectors on the Immunologic Functions of Mouse Dendritic Cells
Authors: Robert J Korst, Ali Mahtabifard, Reiko Yamada, Ronald G Crystal
Journal: Molecular Therapy (2002)

To address the effect of adenovirus (Ad) gene transfer vector transduction on the diverse functions of dendritic cells, we used an Ad vector encoding no transgene (AdNull) to transduce mouse bone-marrow-derived dendritic cells (BMDC). Initial experiments using an Ad vector encoding a marker gene (AdGFP, jellyfish green fluorescent protein) showed that the optimal ratio of infectious Ad particles to each cell was 100, when both transgene expression and resultant BMDC viability were taken into account. Exposure to AdNull resulted in upregulation of both surface activation markers (CD40, MHC class II, B7.1, B7.2, ICAM-1) and IL-12 expression by BMDC. AdNull activation of BMDC was observed in multiple strains of mice. Despite this, AdNull-transduced BMDC displayed only modestly impaired antigen uptake ability, as demonstrated in macropinocytosis and phagocytosis assays, in vitro. However, Ad-modified BMDC migrated to regional lymph nodes five times more efficiently than sham-transduced BMDC in vivo. In addition, Ad transduction significantly enhanced the ability of BMDC to present a model peptide antigen to T-lymphocyte hybridoma cells at low BMDC:T cell ratios. We conclude that Ad modification, in and of itself, induces a state of activation in mouse BMDC. This activation, albeit mild compared with that induced by other stimuli, produces measurable effects of the specific immunological functions of these antigen-presenting cells.
Coffee-Associated Osteoporosis Offset by Daily Milk Consumption
Authors: Elizabeth Barrett-Connor
Journal: JAMA (1994)

To describe the association of lifetime intake of caffeinated coffee, in cup-years, to bone mineral density (BMD) of the hip and spine in postmenopausal women; and to determine the effect of regular milk intake on this association.Women from an established epidemiologic cohort had measures of BMD and gave a medical and behavioral history that included caffeinated coffee and daily milk intake between the ages of 12 and 18 years, 20 and 50 years, and 50 years of age and older.A community-based population of older women, Rancho Bernardo, Calif.All 980 postmenopausal women aged 50 to 98 years (mean age, 72.7 years) who participated between 1988 and 1991.Bone density at the hip and lumbar spine measured by dual energy x-ray absorptiometry.There was a statistically significant graded association between increasing lifetime intake of caffeinated coffee and decreasing BMD at both the hip and spine, independent of age, obesity, parity, years since menopause, and the use of tobacco, alcohol, estrogen, thiazides, and calcium supplements. Bone density did not vary by lifetime coffee intake in women who reported drinking at least one glass of milk per day during most of their adult lives.Lifetime caffeinated coffee intake equivalent to two cups per day is associated with decreased bone density in older women who do not drink milk on a daily basis.
Serratia Marcescens Infection Complicating Peritoneal Dialysis
Authors: A. W. McCracken, F. E. Lipscomb
Journal: BMJ (1965)

Serratia marcescens (Chromobacterium prodigiosum) is a free- living saprophyte generally regarded as being non-pathogenic (Wilson and Miles, 1955).There is, however, reason to believe that under certain conditions this organism may be pathogenic.Three instances are here reported in which S. marcescens infection of the peritoneum occurred during peritoneal dialysis for acute renal failure.All three patients were transferred to Princess Mary's Royal Air Force Hospital, Halton, for manage- mnent of their renal failure.
Cardiomyocyte NF-κB p65 promotes adverse remodelling, apoptosis, and endoplasmic reticulum stress in heart failure
Authors: Tariq Hamid, Shang Z. Guo, Justin R. Kingery, Xilin Xiang, Buddhadeb Dawn, Sumanth D. Prabhu
Journal: Cardiovascular Research (2010)

The role of nuclear factor (NF)-κB in heart failure (HF) is not well defined. We sought to determine whether myocyte-localized NF-κB p65 activation in HF exacerbates post-infarction remodelling and promotes maladaptive endoplasmic reticulum (ER) stress. Non-transgenic (NTg) and transgenic (Tg) mice with myocyte-restricted overexpression of a phosphorylation-resistant inhibitor of κBα (IκBαS32A,S36A) underwent coronary ligation (to induce HF) or sham operation. Over 4 weeks, the remote myocardium of ligated hearts exhibited robust NF-κB activation that was almost exclusively p65 beyond 24 h. Compared with sham at 4 weeks, NTg HF hearts were dilated and dysfunctional, and exhibited hypertrophy, fibrosis, up-regulation of inflammatory cytokines, increased apoptosis, down-regulation of ER protein chaperones, and up-regulation of the ER stress-activated pro-apoptotic factor CHOP. Compared with NTg HF, Tg-IκBαS32A,S36A HF mice exhibited: (i) improved survival, chamber remodelling, systolic function, and pulmonary congestion, (ii) markedly diminished NF-κB p65 activation, cytokine expression, and fibrosis, and (iii) a three-fold reduction in apoptosis. Moreover, Tg-IκBαS32A,S36A HF hearts exhibited maintained expression of ER chaperones and CHOP when compared with sham. In cardiomyocytes, NF-κB activation was required for ER stress-mediated apoptosis, whereas abrogation of myocyte NF-κB shifted the ER stress response to one of adaptation and survival. Persistent myocyte NF-κB p65 activation in HF exacerbates cardiac remodelling by imparting pro-inflammatory, pro-fibrotic, and pro-apoptotic effects. p65 modulation of cell death in HF may occur in part from NF-κB-mediated transformation of the ER stress response from one of adaptation to one of apoptosis.
Functional links between gelatinase B/matrix metalloproteinase-9 and prominin-1/CD133 in diabetic retinal vasculopathy and neuropathy
Authors: Ghulam Mohammad, Jennifer Vandooren, Mohammad Mairaj Siddiquei, Erik Martens, Ahmed M Abu El-Asrar, Ghislain Opdenakker
Journal: Progress in Retinal and Eye Research (2014)
Glycolytic inhibition: effects on diastolic relaxation and intracellular calcium handling in hypertrophied rat ventricular myocytes.
Authors: Y Kagaya, E O Weinberg, N Ito, T Mochizuki, W H Barry, B H Lorell
Journal: Journal of Clinical Investigation (1995)

We tested the hypothesis that glycolytic inhibition by 2-deoxyglucose causes greater impairment of diastolic relaxation and intracellular calcium handling in well-oxygenated hypertrophied adult rat myocytes compared with control myocytes. We simultaneously measured cell motion and intracellular free calcium concentration ([Ca2+]i) with indo-1 in isolated paced myocytes from aortic-banded rats and sham-operated rats. There was no difference in either the end-diastolic or peak-systolic [Ca2+]i between control and hypertrophied myocytes (97 +/- 18 vs. 105 +/- 15 nM, 467 +/- 92 vs. 556 +/- 67 nM, respectively). Myocytes were first superfused with oxygenated Hepes-buffered solution containing 1.2 mM CaCl2, 5.6 mM glucose, and 5 mM acetate, and paced at 3 Hz at 36 degrees C. Exposure to 20 mM 2-deoxyglucose as substitution of glucose for 15 min caused an upward shift of end-diastolic cell position in both control (n = 5) and hypertrophied myocytes (n = 10) (P < 0.001 vs. baseline), indicating an impaired extent of relaxation. Hypertrophied myocytes, however, showed a greater upward shift in end-diastolic cell position and slowing of relaxation compared with control myocytes (delta 144 +/- 28 vs. 55 +/- 15% of baseline diastolic position, P < 0.02). Exposure to 2-deoxyglucose increased end-diastolic [Ca2+]i in both groups (P < 0.001 vs. baseline), but there was no difference between hypertrophied and control myocytes (218 +/- 38 vs. 183 +/- 29 nM, respectively). The effects of 2-deoxyglucose were corroborated in isolated oxygenated perfused hearts in which glycolytic inhibition which caused severe elevation of isovolumic diastolic pressure and prolongation of relaxation in the hypertrophied hearts compared with controls. In summary, the inhibition of the glycolytic pathway impairs diastolic relaxation to a greater extent in hypertrophied myocytes than in control myocytes even in well-oxygenated conditions. The severe impairment of diastolic relaxation induced by 2-deoxyglucose in hypertrophied myocytes compared with control myocytes cannot be explained by greater diastolic Ca2+ overload, which implicates an increase in myofilament Ca(2+)-responsiveness as a possible mechanism.
What Are Sensitized Cells Doing in Glomerulonephritis?
Authors: Frank J. Dixon
Journal: New England Journal of Medicine (1970)

Recent developments in our understanding of cellular hypersensitivity indicate that antibody formation and cellular hypersensitivity commonly accompany each other and that a purely humoral or cellular response is most often an exceptional product of either an abnormal immunologic system or an unusual mode of immunization. Thus, the finding of Rocklin et al. (page 497) that cellular hypersensitivity may accompany the formation of antibody reactive with glomerular basement membrane (GBM) is not unexpected, particularly since GBM or BM antigens are present in both serum and urine of normal and nephritic humans and readily available to all types of immunocompetent cells.1 This . . .