tbuckley/cabot-search huggingface dataset:
Effect of antihypertensive therapy on calcium transport by cardiac sarcoplasmic reticulum of SHRs
Authors: C. J LIMAS, S. S SPIER
Journal: Cardiovascular Research (1980)

Cardiac hypertrophy develops during the course of blood pressure elevation in spontaneously hypertensive rats (SHRs) and is associated with defective calcium transport by cardiac sarcoplasmic reticulum (SR). At 20 weeks of age, calcium uptake is reduced in SHRs (42 ± 1.3 vs 64 ± 1.6 nmol·mg−1·min−1 in age-matched normotensive Wistar-Kyoto rats, P<0.01), while Ca2+ ATPase activity is enhanced (44 ± 1.1 vs 35 ± 0.7 nmol·mg−1·min−1 in WKYs, P = 0.02); this results in low stoichiometry between calcium uptake and ATP hydrolysis in SHRs. The steady-state levels of the phosphoprotein intermediate [EP] of the transport ATPase are higher in normotensive rats (0.97 ± 0.1 vs 0.67 ± 0.08 nmol·mg−1 in SHRs, P <.0.01) but the Ca2+- and ATP-dependency are similar in the two groups. In order to study the relative roles of hypertension and cardiac hypertrophy in the depression of SHR function, 20-week old SHRs and normotensive rats were treated for 10 weeks with either hydralazine (100 mg·litre−1) or α-methyldopa (8 g·litre−1). Both therapeutic regimens resulted in near normalisation of blood pressure of SHRs (hydralazine: 18.1 ± 0.5 kPa [136 ± 4 mmHg]; α-methyldopa 17.6 ± 0.4 kPa [132 ± 3 mmHg]). Regression of cardiac hypertrophy, however, was seen only in the α-methyldopa-treated group, as judged by changes in left ventricular weight, RNA/DNA ratio, and hydroxyproline content. Furthermore, improvement in calcium transport capacity by the SHR, as reflected in higher calcium uptake and stoichiometric ratio between uptake and ATP hydrolysis, was found after a-methyldopa, but not hydralazine, treatment. These results indicate that reversal of cardiac hypertrophy is required for improvement in calcium transport by cardiac SR after antihypertensive therapy of SHRs.
Differential Requirement for SLP-76 Domains in T Cell Development and Function
Authors: Peggy S. Myung, Geo S. Derimanov, Martha S. Jordan, Jennifer A. Punt, Qing-Hua Liu, Barbi A. Judd, Erin E. Meyers, Curt D. Sigmund, Bruce D. Freedman, Gary A. Koretzky
Journal: Immunity (2001)
THE TENDON OF YOUNG ATHLETES AND FOOTBALLERS
Authors: Marucci Ruzza, Xavier Gasol, Xavier Yanguas, Lluis Til
Journal: British Journal of Sports Medicine (2013)

Background Describe patterns of ultrasound and elastography in patellar and achilles tendons in a population of young footballers, jumpers and sprinters. Methods We studied 48 athletes (7 female and 41 male) aged between 15 and 26 years; 24 of them are from a youth soccer team in the national first division and 24 high performance jumpers and sprinters. The information was obtained by Esaote -my lab ultrasound and performed in all cases by the same observer. The 192 tendons were studied in relation to their diameter, presence of vessels within the tendons and their elastography. Results The average diameter was between 4.63 and 4.82 mm including achilles and patellar. Most tendons showed no vessels (88.55%). The elastography pattern was predominantly "medium hard" (in classification by points 0–4, prevailed 2–3) and described the patellar stiffer than achilles. There were 14 tendons equal or larger than 6mm of diameter and 22 tendons were detected with vessels. These last 36 tendons were assessed as pathological status and the 11% of these produced athlete symptoms. Discussion The eco-elastographic screening of athlete's tendons could be used since an early age to detect changes related to diseases occurring along the sporting life. Defining patterns is of great importance because it can be used to detect early changes and it is a way to improve prevention, diagnosis and treatment of these pathologies.
<i>In vitro</i> differentiation of near‐unlimited numbers of functional mouse basophils using conditional Hoxb8
Authors: U. Gurzeler, T. Rabachini, C. A. Dahinden, M. Salmanidis, G. Brumatti, P. G. Ekert, N. Echeverry, D. Bachmann, H. U. Simon, T. Kaufmann
Journal: Allergy (2013)

Abstract Background Basophils constitute a rare leukocyte population known for their effector functions in inflammation and allergy, as well as more recently described immunoregulatory roles. Besides their low frequency, functional analysis of basophils is hindered by a short life span, inefficient ex vivo differentiation protocols, and lack of suitable cell models. A method to produce large quantities of basophils in vitro would facilitate basophil research and constitute a sought‐after tool for diagnostic and drug testing purposes. Methods A method is described to massively expand bone marrow–derived basophils in vitro . Myeloid progenitors are conditionally immortalized using Hoxb8 in the presence of interleukin‐3 ( IL ‐3) and outgrowing cell lines selected for their potential to differentiate into basophils upon shutdown of Hoxb8 expression. Results IL ‐3‐dependent, conditional Hoxb8‐immortalized progenitor cell lines can be expanded and maintained in culture for prolonged periods. Upon shutdown of Hoxb8 expression, near‐unlimited numbers of mature functional basophils can be differentiated in vitro within six days. The cells are end‐differentiated and short‐lived and express basophil‐specific surface markers and proteases. Upon IgE‐ as well as C5a‐mediated activation, differentiated basophils release granule enzymes and histamine and secrete Th2‐type cytokines ( IL ‐4, IL ‐13) and leukotriene C4. IL ‐3‐deprivation induces apoptosis correlating with upregulation of the BH 3‐only proteins BCL‐2‐interacting mediator of cell death ( BIM ) and p53 upregulated modulator of apoptosis ( PUMA ) and downregulation of proviral integration site for Moloney murine leukemia virus 1 kinase (PIM‐1). Conclusion A novel method is presented to generate quantitative amounts of mouse basophils in vitro , which moreover allows genetic manipulation of conditionally immortalized progenitors. This approach may represent a useful alternative method to isolating primary basophils.
Doctors may share genetic information to help patients' relatives
Authors: C. Dyer
Journal: BMJ (2009)

Clinical geneticists and medical ethicists have welcomed guidance from the General Medical Council that says that doctors may share confidential genetic information to protect a patient’s relatives, even if the patient objects.

The guidance focuses explicitly for the first time on genetic information that could benefit a family member as a possible exception to the rule that patients’ data must be kept confidential.

Previous advice in 2004 stated only the broad rule that doctors could disclose patients’ data if the benefits to an individual or society outweighed the public’s and the patient’s interest in keeping the information confidential.

The new advice follows advances in medical science and a recommendation by the …
Asthma, Wheezy Bronchitis, and Atopy across Two Generations
Authors: G. L. CHRISTIE, P. J. HELMS, D. J. GODDEN, S. J. ROSS, J. A. R. FRIEND, J. S. LEGGE, N. E. HAITES, J. G. DOUGLAS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Although the prevalence of asthma has risen significantly during the last 30 yr, it is not clear whether this has occurred primarily in persons with a strong genetic predisposition to asthma and atopy or in other sections of the population. We have investigated outcomes in children of nuclear families selected through probands previously characterized by studies in 1964 and 1989 as having histories of persistent childhood onset atopic asthma, transient childhood wheezy bronchitis, and no respiratory symptoms or atopy. Children of wheezy bronchitic probands had a significantly better symptomatic outcome in adolescence, irrespective of the atopic status of the parent proband, than do children of either asthmatic or asymptomatic probands, suggesting that this may be a syndrome that shows familial aggregation and is distinct from asthma. Total serum IgE levels were significantly lower in children of nonatopic asymptomatic probands, including those with wheezing symptoms. In contrast children of nonatopic asymptomatic probands had an unexpectedly high prevalence of wheezing (33%), positive skin prick tests (56%), and positive specific serum IgE to common allergens (48%) that was similar to that found in children of atopic asthmatic probands. Our findings support the concept that wheezy bronchitis is a separate syndrome from atopic asthma. High total serum IgE levels within our population appear to be an important marker of genetic predisposition to atopy. Our data also suggest that much of the increase in asthma prevalence is associated with specific IgE sensitization and is occurring in persons previously considered to be at low risk of developing asthma or atopy.
Modulation of Laminin Receptor Expression by Estrogen and Progestins in Human Breast Cancer Cell Lines
Authors: V. Castronovo, G. Taraboletti, L. A. Liotta, M. E. Sobel
Journal: JNCI Journal of the National Cancer Institute (1989)

The effects of estradiol and two synthetic progestins (ORG2058 and R5020) on the expression of the high-affinity, metastasis-associated laminin receptor in two human breast carcinoma cell lines were examined. The T47D cell line contains estrogen and progesterone receptors, but the MDA-MB 231 cell line lacks both receptors. Treatment of T47D cells with 10−9M estradiol alone results in a three-fold increase (P ≤.05) in the steady-state level of laminin receptor mRNA determined by RNA blot analysis as well as in cell-surface, laminin receptor expression that is evaluated by immunofluorescence. No effects of estradiol on the receptor-negative MDA-MB 231 cells were observed. Untreated and steroid-treated MDA-MB 231 cells had higher levels of laminin receptor mRNA than did untreated or estradiol-treated T47D cells. A more dramatic increase (fivefold; P ≤.005) of mRNA and cell-surface expression in T47D cells was observed after treatment with estradiol plus 10−8M progestin or with progestin alone. Estradiol treatment also increased chemotaxis and haptotaxis of T47D cells but not of MDA-MB 231 cells to laminin; it had no effect on the attachment of these latter cells to laminin. Interestingly, treatment with estradiol plus progestin or progestin alone significantly increased the attachment of T47D cells to laminin but did not have an effect on either haptotaxis or chemotaxis to laminin. These results suggest that the various cell-laminin interactions are mediated by different mechanisms. The augmentation of laminin receptor mRNA by estrogen and progesterone treatment in hormone receptor-positive cells, but not in cells that lack these receptors, may relate functionally to the difference in the clinical aggressiveness between classes of breast cancers.
Endoscopic Therapy of Benign Anastomotic Strictures of the Colorectum by Electroincision and Balloon Dilatation
Authors: S. Truong, S. Willis, V. Schumpelick
Journal: Endoscopy (1997)

Endoscopic dilatation is the standard therapy for postoperative colorectal anastomotic strictures, although it carries the risk of perforation at the weakest part of the anastomosis. In order to minimize this risk we have developed a combined technique of endoscopic electroincision and hydraulic balloon dilatation.Thirty-six symptomatic patients with benign colorectal anastomotic strictures were referred for endoscopic electroincision with consecutive balloon dilatation, if the diameter of the anastomosis was less than 12 mm (n = 15) or if the diameter was less than 20 mm and the patient complained of repeated obstructive symptoms under conservative therapy (n = 21). Under direct endoscopic control the scar tissue at the anastomotic line was incised radially with the tip of the polypectomy snare or with a papillotome. Endoscopic hydraulic balloon dilatation was then performed, using a pressure of 35 PSI for three minutes. An endoscopic or radiological control was carried out on the second day, and balloon dilatation was repeated if necessary.The combined technique of electroincision and consecutive balloon dilatation was performed successfully in 35 patients. In only one patient this therapy could not be performed, because of a long stenotic segment, and surgery was necessary. In 24 patients one single dilatation was sufficient after electroincision, whereas six patients required two, and five patients required three consecutive balloon dilatations. There were no severe complications such as bleeding or perforation. Complete follow-up evaluation was possible in 25 patients. In five cases recurrences appeared within the first year; all could be treated successfully by further balloon dilatation.The combination of endoscopic electroincision and hydraulic balloon dilatation leads to a high long-term clinical success with a minimum of complications. Therefore, in our opinion it is a useful method in the treatment of benign colorectal anastomotic strictures.
Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats
Authors: Peter Skov Olsen, Steen Boesby, Preben Kirkegaard, Kim Therkelsen, Thomas Almdal, Steen Seier Poulsen, Ebba Nexø
Journal: Hepatology (1988)

The role of epidermal growth factor on liver regeneration after partial hepatectomy in rats was investigated. After a 70% hepatectomy in rats, the concentration of epidermal growth factor in portal venous blood was unchanged compared with unoperated controls. However, small amounts of epidermal growth factor could be identified in portal venous blood after intestinal instillation of epidermal growth factor. Brunner’s glands and the submandibular glands secrete epidermal growth factor. Extirpation of Brunner’s glands decreased liver regeneration, whereas removal of the submandibular glands had no effect on liver regeneration. Epidermal growth factor antiserum reduced liver regeneration significantly. Oral or s.c. administration of epidermal growth factor had no effect on liver regeneration, whereas epidermal growth factor enhanced the effect of insulin and glucagon on liver regeneration. The results suggest that endogenous epidermal growth factor participates in stimulation of liver regeneration after partial hepatectomy in rats. Epidermal growth factor given together with insulin and glucagon had a synergistic effect on liver regeneration which suggests that liver regeneration in the rat is controlled by multiple regulatory peptides.
Cloudy Crystal Balls Do Not “Gray” Babies Make
Authors: Anita Silvers, Leslie Francis
Journal: The American Journal of Bioethics (2011)

Click to increase image sizeClick to decrease image size Notes 1. In this piece, we do not aim to argue against all possible proposals to invoke a morally gray area. Our target is Wilkinson's reliance on uncertainty about futures as at least one important reason to propel infants into the gray zone. 2. Notably, Wilkinson does not construe the standpoint in the same way in considering the case of infants supposed to be in group 3, with lives in which the overall burdens will be greater than the benefits. In such cases, the overall burdens are not construed as attenuated because of the infant's limited awareness or seen as limited to a transient cognitive state. Readers may recall that as an infant the future king Oedipus was left to die because at his birth it was prophesied that he would commit patricide. For example, a recent study of neonates concludes that low Apgar scores are highly associated with future findings of cerebral palsy in infants of normal birth weight but perhaps surprisingly only modestly associated with cerebral palsy in infants of low birth weight (Lie, Grøholt, and Eskild 2010).
SYNERGISTIC IMPACT OF CHRONIC KIDNEY DISEASE AND DIABETES MELLITUS ON PERIPHERAL VASCULAR ATHEROSCLEROTIC PLAQUE NEOVASCULARIZATION AND INFLAMMATION
Authors: Usman Baber, K-Raman Purushothaman, Prakash Krishnan, Meerarani Purushothaman, Jason C. Kovacic, Roxana Mehran, George Dangas, Annapoorna Kini, Samin Sharma, Pedro Moreno
Journal: Journal of the American College of Cardiology (2012)
Gold nanoparticles surface-functionalized with paclitaxel drug and biotin receptor as theranostic agents for cancer therapy
Authors: Dong Nyoung Heo, Dae Hyeok Yang, Ho-Jin Moon, Jung Bok Lee, Min Soo Bae, Sang Cheon Lee, Won Jun Lee, In-Cheol Sun, Il Keun Kwon
Journal: Biomaterials (2011)
Silencing of HIV-1 with RNA Interference: a Multiple shRNA Approach
Authors: Olivier ter Brake, Pavlina Konstantinova, Mustafa Ceylan, Ben Berkhout
Journal: Molecular Therapy (2006)

Double-stranded RNA can induce gene silencing via a process known as RNA interference (RNAi). Previously, we have shown that stable expression of a single shRNA targeting the HIV-1 Nef gene strongly inhibits HIV-1 replication. However, this was not sufficient to maintain inhibition. One of the hallmarks of RNAi, its sequence specificity, presented a way out for the virus, as single nucleotide substitutions in the target region abolished inhibition. For the development of a durable gene therapy that prevents viral escape, we proposed to combine multiple shRNAs against conserved HIV-1 regions. Therefore, we screened 86 different shRNAs targeting highly conserved regions. We identified multiple shRNAs that act as potent inhibitors of virus replication. We show, for the first time, that expression of three different shRNAs from a single lentiviral vector results in similar levels of inhibition per shRNA compared to single shRNA vectors. Thus, their combined expression results in a much stronger inhibition of virus production. Moreover, when we infected cells transduced with a double shRNA viral vector, virus escape was delayed. These results confirm that RNAi has great potential as an antiviral gene therapy approach and support our efforts to develop this strategy for treatment of HIV-1-infected individuals.
Uptake and Costs of Hypofractionated vs Conventional Whole Breast Irradiation After Breast Conserving Surgery in the United States, 2008–2013
Authors: Justin E. Bekelman, Gosia Sylwestrzak, John Barron, Jinan Liu, Andrew J. Epstein, Gary Freedman, Jennifer Malin, Ezekiel J. Emanuel
Journal: JAMA (2014)

Based on randomized evidence, expert guidelines in 2011 endorsed shorter, hypofractionated whole breast irradiation (WBI) for selected patients with early-stage breast cancer and permitted hypofractionated WBI for other patients.To examine the uptake and costs of hypofractionated WBI among commercially insured patients in the United States.Retrospective, observational cohort study, using administrative claims data from 14 commercial health care plans covering 7.4% of US adult women in 2013, we classified patients with incident early-stage breast cancer treated with lumpectomy and WBI from 2008 and 2013 into 2 cohorts: (1) the hypofractionation-endorsed cohort (n = 8924) included patients aged 50 years or older without prior chemotherapy or axillary lymph node involvement and (2) the hypofractionation-permitted cohort (n = 6719) included patients younger than 50 years or those with prior chemotherapy or axillary lymph node involvement.Hypofractionated WBI (3-5 weeks of treatment) vs conventional WBI (5-7 weeks of treatment).Use of hypofractionated and conventional WBI, total and radiotherapy-related health care expenditures, and patient out-of-pocket expenses. Patient and clinical characteristics included year of treatment, age, comorbid disease, prior chemotherapy, axillary lymph node involvement, intensity-modulated radiotherapy, practice setting, and other contextual variables.Hypofractionated WBI increased from 10.6% (95% CI, 8.8%-12.5%) in 2008 to 34.5% (95% CI, 32.2%-36.8%) in 2013 in the hypofractionation-endorsed cohort and from 8.1% (95% CI, 6.0%-10.2%) in 2008 to 21.2% (95% CI, 18.9%-23.6%) in 2013 in the hypofractionation-permitted cohort. Adjusted mean total health care expenditures in the 1 year after diagnosis were $28,747 for hypofractionated and $31,641 for conventional WBI in the hypofractionation-endorsed cohort (difference, $2894; 95% CI, $1610-$4234; P < .001) and $64,273 for hypofractionated and $72,860 for conventional WBI in the hypofractionation-permitted cohort (difference, $8587; 95% CI, $5316-$12,017; P < .001). Adjusted mean total 1-year patient out-of-pocket expenses were not significantly different between hypofractionated vs conventional WBI in either cohort.Hypofractionated WBI after breast conserving surgery increased among women with early-stage breast cancer in 14 US commercial health care plans between 2008 and 2013. However, only 34.5% of patients with hypofractionation-endorsed and 21.2% with hypofractionation-permitted early-stage breast cancer received hypofractionated WBI in 2013.
Liver Damage from Oral Contraceptives
Authors: B. A. Stoll, J. T. Andrews, R. Motteram
Journal: BMJ (1966)

15 patients were investigated for Lyndiol (lynestrenol and mestranol) related liver dysfunction.  4 postmenopausal patients received 6 tablets a day of Lyndiol for cancer therapy.  They showed a gross rise in serum glutamic oxalacetic transaminase levels after 2 weeks therapy.  Liver biopsy showed parenchymal cell necrosis.  In 2 women the liver function tests returned to normal within 8 weeks of cessation of the drugs.  7 women received 30mg lynestrenol alone and 4 women were given .9mg mestranol alone to determine the contribution of each drug to the effects seen in liver function.  Only the progesterone produced abnormal liver function tests.  The presence of an alkylated group in the C17 position is the steroid configuration which is apt to induce hepatic damage and cholestasis when the drug is given in sufficient dosage for prolonged periods.
Clinical relevance of vertebral fractures
Authors: W F Lems
Journal: Annals of the Rheumatic Diseases (2006)

Why are vertebral fractures so often overlooked?

Osteoporotic fractures occur quite frequently: the lifetime fracture risk for a 50-year-old woman is 40%.1 Bone mineral density (BMD) is an important predictor of future fractures: the risk is increased twofold for each standard deviation (SD) decrease in BMD, whereas the correlation between low BMD and fractures is strongest for measurements at the same site as that of the fracture.2 BMD is often measured for diagnosing osteoporosis (T score ⩽−2.5 SD, according to the World Health Organization criteria), although these criteria were developed for epidemiological studies. However, the two-dimensional dual-energy x ray absorptiometry images do not measure two other important properties of bone strength: the microarchitecture and its material composition.3

In a large meta-analysis, it has been shown that having a fracture is associated with an increased relative risk of subsequent fractures.4 In Maastricht, The Netherlands, a large study on 2419 patients aged ⩾50 years was performed: the absolute risk of developing a new clinical fracture within 2 years after a fracture was >10%.5 In Glasgow, UK, a low BMD was found in 50–70% of the patients aged ⩾50 years with a clinical (nearly all non-vertebral) fracture.6 As effective osteoporosis drugs, particularly bisphosphonates, are nowadays available,7 awareness is growing that patients should be diagnosed and treated for osteoporosis in the case of a low BMD, particularly in combination with a clinical (non-vertebral) fracture.

The first reason for failing to diagnose vertebral fractures is its clinical presentation: non-vertebral fractures, for example, from the wrist or hip, are easy to diagnose in patients with severe pain and a deformity, usually after a fall. By contrast, diagnosing vertebral fractures is more complicated. They usually occur during daily activities, such as climbing stairs or bending forward, without a fall. The …