tbuckley/cabot-search huggingface dataset:
The GRACILE mutation introduced into Bcs1l causes postnatal complex III deficiency: A viable mouse model for mitochondrial hepatopathy
Authors: Per Levéen, Heike Kotarsky, Matthias Mörgelin, Riitta Karikoski, Eskil Elmér, Vineta Fellman
Journal: Hepatology (2010)

Mitochondrial dysfunction is an important cause for neonatal liver disease. Disruption of genes encoding oxidative phosphorylation (OXPHOS) components usually causes embryonic lethality, and thus few disease models are available. We developed a mouse model for GRACILE syndrome, a neonatal mitochondrial disease with liver and kidney involvement, caused by a homozygous BCS1L mutation (232A>G). This gene encodes a chaperone required for incorporation of Rieske iron-sulfur protein (RISP) into complex III of respiratory chain. Homozygous mutant mice after 3 weeks of age developed striking similarities to the human disease: growth failure, hepatic glycogen depletion, steatosis, fibrosis, and cirrhosis, as well as tubulopathy, complex III deficiency, lactacidosis, and short lifespan. BCS1L was decreased in whole liver cells and isolated mitochondria of mutants at all ages. RISP incorporation into complex III was diminished in symptomatic animals; however, in young animals complex III was correctly assembled. Complex III activity in liver, heart, and kidney of symptomatic mutants was decreased to 20%, 40%, and 40% of controls, respectively, as demonstrated with electron flux kinetics through complex III. In high-resolution respirometry, CIII dysfunction resulted in decreased electron transport capacity through the respiratory chain under maximum substrate input. Complex I function, suggested to be dependent on a functional complex III, was, however, unaffected. Conclusion: We present the first viable model of complex III deficiency mimicking a human mitochondrial disorder. Incorporation of RISP into complex III in young homozygotes suggests another complex III assembly factor during early ontogenesis. The development of symptoms from about 3 weeks of age provides a convenient time window for studying the pathophysiology and treatment of mitochondrial hepatopathy and OXPHOS dysfunction in general. (HEPATOLOGY 2011:53:437-447.)
Monoclonal Antibodies Produced by Muscle after Plasmid Injection and Electroporation
Authors: Torunn Elisabeth Tjelle, Alexandre Corthay, Elin Lunde, Inger Sandlie, Terje E Michaelsen, Iacob Mathiesen, Bjarne Bogen
Journal: Molecular Therapy (2004)

Antibodies are useful for the treatment of a variety of diseases. We here demonstrate that mouse muscle produced monoclonal antibodies (mAb) after a single injection of immunoglobulin genes as plasmid DNA. In vivo electroporation of muscle greatly enhanced antibody production. For chimeric antibodies, levels of 50–200 ng mAb/ml serum were obtained but levels declined after 7–14 days due to an immune response against the xenogeneic parts of the antibody. By contrast, fully mouse antibodies persisted in serum for at least 7 months. mAb produced by the muscle had correct structure, specificity, and biological effector functions. The findings were extended to a larger animal, the sheep, in which mAb serum levels of 30–50 ng/ml were obtained. Sustained levels of serum mAb, induced by single injection of Ig genes and electroporation of muscle cells, may offer significant advantages in the treatment of human diseases.
Nonremovable, Windowed, Fiberglass Cast Boot in the Treatment of Diabetic Plantar Ulcers
Authors: Georges Ha Van, Hubert Siney, Agnes Hartmann-Heurtier, Sophie Jacqueminet, Françoise Greau, André Grimaldi
Journal: Diabetes Care (2003)

OBJECTIVE—To compare the efficacy, safety, and compliance of a nonremovable fiberglass cast boot and off-loading shoes in the treatment of diabetic plantar ulcers. RESEARCH DESIGN AND METHODS—Patients (n = 93) with noninfected, nonischemic plantar ulcers were included in this prospective nonrandomized study. Treatment used a nonremovable fiberglass cast boot for longer standing and deeper ulcers (n = 42) and a half shoe or heel-relief shoe for other ulcers (n = 51). We evaluated off-loading therapy, compliance, and complications in both groups. RESULTS—The healing rate was significantly higher with the cast boot than with the off-loading shoe (81 vs. 70%, P = 0.017), with healing times of 68.6 ± 35.1 vs. 134.2 ± 133.0 days, respectively, and hazard ratio 1.68 (95% CI 1.04–2.70); complete compliance with treatment was 98 vs. 10% (P = 0.001), respectively. Secondary osteomyelitis developed in 3 patients in the cast boot group and 13 patients in the off-loading shoe group (P = 0.026). CONCLUSIONS—A nonremovable fiberglass cast boot was effective in healing diabetic plantar ulcers and in decreasing the risk of secondary osteomyelitis. The cast boot forced compliance with off-loading, thus promoting healing.
REGULATION OF DELAYED HYPERSENSITIVITY
Authors: J. M. Dwyer, F. S. Kantor
Journal: The Journal of Experimental Medicine (1973)

Two potential mechanisms for terminating delayed hypersensitivity (DH) reactions have been examined in desensitized guinea pigs. Lack of macrophage responsiveness to lymphokines was sought as an explanation for the reduced ability of these animals to express delayed hypersensitivity. Skin-reactive factor was injected into the skin of desensitized guinea pigs and a control group of similarly immunized animals. The resulting inflammatory reactions were similar in size and intensity in both groups indicating normal macrophage responsiveness in the desensitized state. Passive cellular transfer of DH responses to desensitized animals was markedly less successful than transfer to normal animals. However, cells from desensitized guinea pigs did transfer DH responsiveness to normal animals. These data support the concept of a humoral suppressant of cellular immunity, perhaps acting as a feedback inhibitor, produced when guinea pigs are desensitized.
Inhaled corticosteroids: first do no harm
Authors: V. H. F. Mak
Journal: BMJ (2012)

Mackenzie highlights the lack of guidance on use of inhaled corticosteroids (ICS) and risk of adrenal suppression.1 The Medicines and Healthcare Products Regulatory Agency recommends issuing a steroid treatment card,2 but there is concern that this may alarm patients and reduce adherence. There is also no consensus on what constitutes a high dose.

High potency combination inhalers (ICS …
Reflections and best practice recommendations for interdisciplinary working: a case study on the identification of the determinants of addiction from the Addiction and Lifestyles In Contemporary Europe Reframing Addictions Project (ALICE RAP)
Authors: Lucy Gell, Jane McLeod, John Holmes, Emma Everson-Hock, Gerhard Buehringer, Anne Lingford-Hughes, Maria Neumann, Petra Meier
Journal: The Lancet (2014)
THE PRINCIPLE OF LIFE.
Authors: MARSHALL LANGTON PRICE
Journal: JAMA (1905)

"The days of our age are three score years and ten; and though men be so strong that they come to four score years, yet is their strength then but labor and sorrow, so soon it passeth away and we are gone." To many of us who travel along the level, but somewhat narrow pathway of scientific research, there doubtless comes the desire, to leave its beaten surface and to stray in those bordering fields where fact and fancy are so delightfully intermingled; where the skies are always blue, the sunshine bright, and the flowers fresh and blooming; where substance appears as shadow and shadow substance and our pet hobbies, viewed with our indulgent paternal eyes, seem beautiful and spirited thoroughbreds. In this land, we can appropriately ask, in the words of the cynical Roman Governor of Judea (freed from the rigid limitations which science imposes), "What is truth?" An
Lactation after Incision on the Thoracic Cage
Authors: Robert L. Berger, Julio Joison, Lewis E. Braverman
Journal: New England Journal of Medicine (1966)

THE onset of lactation in the early postoperative period after incisions on the chest wall is an unexpected event both to the patient and to the surgeon. A few days after surgery, either one or both breasts engorge; lactation begins soon thereafter and persists for months or even years. It is usually associated with lateral thoracic incisions and is not accompanied by amenorrhea. This phenomenon has been reported only rarely.1 2 3 We have recently observed 3 patients with postoperative lactation; 1 case followed a lateral thoracic incision, 1 was associated with a stab wound of the chest, and 1 occurred after . . .
Clinical Indicators of Left Main Coronary Artery Disease in Unstable Angina
Authors: G D Plotnick, H L Greene, N H Carliner, L C Becker, M L Fisher
Journal: Annals of Internal Medicine (1979)

Two hundred consecutive catheterized patients with unstable angina pectoris were reviewed to find clinical and noninvasive indicators of left main coronary artery disease (≥ 50% lesion). Thirty-five patients (17.5% of total) had left main coronary artery disease. There were no differences between patients with and without left main coronary artery disease in age, sex, results of resting electrocardiogram, congestive heart failure, dyspnea during pain, duration of longest pain, arrhythmias, response to medical therapy, or other risk factors. Crescendo angina pectoris (worsening of pre-existing angina), transient ST-segment depression with pain, simultaneous anterior and inferior ST changes during pain, and fluoroscopic calcification of the left main coronary artery were all significantly more common in patients with left main coronary artery disease. However, low sensitivity or low predictive value, or both, limit the usefulness of these clinical predictors. Left main coronary artery disease cannot be reliably predicted in patients with unstable angina pectoris before coronary arteriography.
Ethics and Communication in Do-Not-Resuscitate Orders
Authors: T Tomlinson, H Brody
Journal: New England Journal of Medicine (1988)

Despite the extensive literature devoted to do-not-resuscitate (DNR) orders, they continue to raise vexing problems for physicians, house staff, nurses, and policy makers. The difficulties include physicians' ambivalence about who should be consulted before a DNR order is written, the frustration of house officers and nurses who are asked to continue complicated or invasive treatments of a patient for whom a DNR order has been written, and hospital administrators' uncertainty and confusion over what their DNR policies should be.Many of these problems arise from the failure to distinguish among three distinct rationales for DNR orders and to appreciate their . . .
Diagnosing Spinal Osteomyelitis
Authors: CHARITO LOVE, MAHENDRA PATEL, BARON S. LONNER, MARIA B. TOMAS, CHRISTOPHER J. PALESTRO
Journal: Clinical Nuclear Medicine (2000)

Purpose The objective of this investigation was to compare the accuracies of bone and Ga-67 scintigraphy and magnetic resonance imaging (MRI) for diagnosing spinal osteomyelitis and to determine the optimal radionuclide approach to this disorder. Methods Twenty-two patients, with 24 sites of possible spinal osteomyelitis, who underwent three-phase bone scintigraphy with SPECT, Ga-67 scintigraphy with SPECT, and MRI with and without contrast were included in this retrospective review. Bone scans were interpreted as three-phase studies, delayed planar images alone, delayed planar plus SPECT, and SPECT alone (to identify uptake patterns). Sequential bone/ Ga-67 images were interpreted as planar and as SPECT studies. Planar and SPECT Ga-67 images were also interpreted alone. Precontrast MRI studies were used to identify osteomyelitis, whereas postcontrast images were used to identify soft tissue infection. Results Eleven sites of spinal osteomyelitis were identified. Tracer uptake in two contiguous vertebrae, as noted on SPECT, was the most accurate bone scan criterion for detecting spinal osteomyelitis (71%). SPECT bone/Ga-67 was significantly more accurate (92%) than both planar bone/Ga-67 (75%) and bone SPECT (P = 0.15 and P = 0.2, respectively). SPECT Ga-67 was as accurate as SPECT bone/Ga-67 and as sensitive as MRI (91%); the radionuclide study was slightly but not significantly more specific (92% vs. 77%) than MRI. Of 11 sites of extraosseous infection, 10 were identified on MRI, 9 on SPECT Ga-67, 7 on planar Ga-67, and none on bone scintigraphy. Conclusions Spinal osteomyelitis and accompanying soft tissue infection can be diagnosed accurately with a single radionuclide procedure: SPECT Ga-67. This procedure can be used as a reliable alternative when MRI cannot be performed and as an adjunct in patients in whom the diagnosis is uncertain.
4% lidocaine gel applied to the breasts before screening mammography reduced discomfort
Authors: Chris Del Mar
Journal: Annals of Internal Medicine (2008)

ACP Journal ClubNovember 18, 20084% lidocaine gel applied to the breasts before screening mammography reduced discomfortChris Del Mar, MDChris Del Mar, MDBond University, Gold Coast, Queensland, Australia (C.D.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-10-200811180-02009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLambertz CK, Johnson CJ, Montgomery PG, Maxwell JR. Premedication to reduce discomfort during screening mammography. Radiology. 2008;248:765-72. https://pubmed.ncbi.nlm.nih.gov/18647845Clinical Impact RatingsGIM/FP/GP: Oncology: References1 Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev. 2006;(4):CD001877. [PMID: 17054145] Google Scholar2 Schonberg MA, McCarthy EP, York M, Davis RB, Marcantonio ER. Factors influencing elderly women's mammography screening decisions: implications for counseling. BMC Geriatr. 2007;7:26. [PMID: 18021402] Google Scholar3 Miller D, Livingstone V, Herbison P. Interventions for relieving the pain and discomfort of screening mammography. Cochrane Database Syst Rev. 2008;(1):CD002942 Google Scholar Author, Article, and Disclosure InformationAffiliations: Bond University, Gold Coast, Queensland, Australia (C.D.M.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics November 18, 2008Volume 149, Issue 10Page: JC5-9KeywordsAnalgesicsBreast cancerKidneysLiverMammographyNursesRadiologistsTechniciansThorax ePublished: 10 March 2020 Issue Published: November 18, 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson disease (the systemic capillary leak syndrome)
Authors: Zhihui Xie, Chandra C. Ghosh, Roshni Patel, Shoko Iwaki, Donna Gaskins, Celeste Nelson, Nina Jones, Philip R. Greipp, Samir M. Parikh, Kirk M. Druey
Journal: Blood (2012)
Biopersistence of nonfibrous mineral particles in the respiratory tracts of subjects following occupational exposure.
Authors: J C Pairon, M A Billon-Galland, Y Iwatsubo, M Bernstein, A Gaudichet, J Bignon, P Brochard
Journal: Environmental Health Perspectives (1994)

Transmission electron microscopy analysis (TEMA) was used to analyze the bronchoalveolar lavage fluid (BALF) of 262 subjects occupationally exposed (OE) to nonfibrous mineral particles (NFMP) and 42 controls not occupationally exposed to mineral dusts. OE subjects were divided into three groups according to the lapse of time since last exposure: < or = 1 year and < 10 years (E2), > or = 10 years (E3). The total BALF mineral particle concentration was significantly higher in OE patients than in controls and was closely related to the time lapse since last exposure to NFMP (median values for OE, 7.7 x 10(5) particles/ml; E1, 9 x 10(5) particles/ml; E2, 5 x 10(5) particles/ml; E3, 4.3 x 10(5) particles/ml; controls, 2 x 10(5) particles/ml). No statistical difference was observed for age and smoking habits between OE and control subjects. Concentrations of crystalline silica and metals (exogenous iron, aluminum, metallic alloys and other metals) were significantly higher in OE subjects than in controls, and even though these mineral concentrations decreased with increasing time since last occupational exposure, they still remained higher in the E3 group than in controls. Crystalline silica and metals were thus identified as biopersistent NFMP in the human lung using BALF ATEM method. This method is a useful tool in assessing occupational exposure to NFMP, even when a long period has elapsed since last exposure, and may be used in studying etiology of some respiratory diseases.
Abstract LB-225: Resistance to paclitaxel in triple negative breast cancer cells is associated with ABCB1 overexpression and gene amplification, and can be reversed by anti-EGFR targeting.
Authors: Elaheh Ahmadzadeh, Ewa Przybytkowski, Adriana Aguilar-Mahecha, Mark Basik
Journal: Cancer Research (2013)

Abstract Background: Due to the absence of expression of estrogen, progesterone and HER2 receptors, triple negative breast cancer (TNBC) patients do not benefit from targeted therapies. Therefore, chemotherapy remains the only treatment of choice for patients with TNBC. Despite initial clinical responses to chemotherapy, the majority of TNBC patients acquire resistance and develop progressive disease. There is little data about mechanisms of resistance to chemotherapy in TNBCs. Methods: We investigated the molecular mechanisms of acquired resistance to paclitaxel (PTX) in TNBCs. Four TNBC cell lines (BT20, SUM149, MA-MB-231 and MDA-MB-436) were cultured in the presence of increasing concentrations of paclitaxel until they acquired resistance. Gene expression and aCGH analysis were performed on all parental and resistant pairs. Results: We found a novel amplification of the ABCB1 gene in BT20 and SUM149 resistant cell lines only. Gene expression analysis revealed significant up-regulation of expression of ABCB1 and EGFR ligands in SUM149 and BT20 resistant cells compared to parental cell lines. The functional activity of ABC transporters assessed using rhodamine 123 efflux assay demonstrated a marked increase in the efflux of rhodamine in SUM149-R and BT20-R which was reversed by verapamil. We treated resistant cells with two anti-EGFR drugs, lapatinib and neratinib, which are also known ABC transporter inhibitors, and found that both drugs inhibited rhodamine 123 efflux and restored sensitivity to PTX in these PTX-resistant TNBC cells. Conclusion: This is the first report of ABCB1 gene amplification in paclitaxel resistant triple negative breast cancer cells. Our results suggest that ABCB1 gene amplification and EGFR ligand over-expression plays a critical role in the development of PTX resistance in TNBC cells, and that this resistance can be targeted by therapy with anti-EGFR agents. Thus, ABCB1 gene amplification and EGFR ligand expression may be novel predictive biomarkers for both chemotherapy and anti-EGFR therapy in TNBCs. Citation Format: Elaheh Ahmadzadeh, Ewa Przybytkowski, Adriana Aguilar-Mahecha, Mark Basik. Resistance to paclitaxel in triple negative breast cancer cells is associated with ABCB1 overexpression and gene amplification, and can be reversed by anti-EGFR targeting. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-225. doi:10.1158/1538-7445.AM2013-LB-225
Low expression of calponin in smooth muscle cells of coronary artery lesions identifies the high risk for restenosis after directional coronary atherectomy
Authors: Hidemasa Oh, Masanobu Funamoto, Etsuo Tsuchikane, Nobuyuki Negoro, Toru Kobayashi, Katsuhito Takahashi, Nobuhisa Awata
Journal: Journal of the American College of Cardiology (1996)
Formula fever: allocating resources in the NHS
Authors: T. A Sheldon
Journal: BMJ (1997)

A new set of weighted capitation formulas are being used for allocating resources to health service “purchasers.” Since the 1970s the NHS has used formulas to promote a more equitable allocation of resources for hospital and community care. The Resource Allocation Working Party (RAWP) recommended that cash should be distributed on the basis of the size and age-sex distribution of an area's population, taking into account relative health care needs as indicated by its standardised mortality ratio.1 This highlighted the fact that the regions in the south of England were receiving more than their fair share of resources and initiated a gradual redistribution to the poorer and sicker north.

In the 1980s regression analysis was used to estimate the influence of health and socioeconomic factors on health care use.2 Recent research at York University used more statistically appropriate techniques which also adjust better …
CRF receptor 1 regulates anxiety behavior via sensitization of 5-HT2 receptor signaling
Authors: Ana C. Magalhaes, Kevin D. Holmes, Lianne B. Dale, Laetitia Comps-Agrar, Dennis Lee, Prem N. Yadav, Linsay Drysdale, Michael O. Poulter, Bryan L. Roth, Jean Philippe Pin, Hymie Anisman, Stephen S G Ferguson
Journal: Nature Neuroscience (2010)
Effects on birth weight and perinatal mortality of maternal dietary supplements in rural gambia: 5 year randomised controlled trial
Authors: S. M Ceesay, A. M Prentice, T. J Cole, F. Foord, E. M E Poskitt, L. T Weaver, R. G Whitehead
Journal: BMJ (1997)

To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system.5 year controlled trial of all pregnant women in 28 villages randomised to daily supplementation with high energy groundnut biscuits (4.3 MJ/day) for about 20 weeks before delivery (intervention) or after delivery (control).Rural Gambia.Chronically undernourished women (twin bearers excluded), yielding 2047 singleton live births and 35 stillbirths.Birth weight; prevalence of low birth weight (< 2500 g); head circumference; birth length; gestational age; prevalence of stillbirths; neonatal and postneonatal mortality.Supplementation increased weight gain in pregnancy and significantly increased birth weight, particularly during the nutritionally debilitating hungry season (June to October). Weight gain increased by 201 g (P < 0.001) in the hungry season, by 94 g (P < 0.01) in the harvest season (November to May), and by 136 g (P < 0.001) over the whole year. The odds ratio for low birthweight babies in supplemented women was 0.61 (95% confidence interval 0.47 to 0.79, P < 0.001). Head circumference was significantly increased (P < 0.01), but by only 3.1 mm. Birth length and duration of gestation were not affected. Supplementation significantly reduced perinatal mortality: the odds ratio was 0.47 (0.23 to 0.99, P < 0.05) for stillbirths and 0.54 (0.35 to 0.85, P < 0.01) for all deaths in first week of life. Mortality after 7 days was unaffected.Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers. This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality. The intervention can be successfully delivered through a primary healthcare system.
61 ONCE DAILY PSI-7977 PLUS PEGIFN/RBV IN A PHASE 2B TRIAL: RAPID VIROLOGIC SUPPRESSION IN TREATMENT-NAIVE PATIENTS WITH HCV GT2/GT3
Authors: J. Lalezari, E. Lawitz, M. Rodriguez-Torres, A. Sheikh, B. Freilich, D.R. Nelson, T. Hassanein, M. Mader, E. Albanis, W. Symonds, M.M. Berrey
Journal: Journal of Hepatology (2011)