tbuckley/cabot-search huggingface dataset:
Dopamine does not enhance furosemide-induced natriuresis in patients with congestive heart failure.
Authors: D L Vargo, D C Brater, D W Rudy, S K Swan
Journal: Journal of the American Society of Nephrology (1996)

The objective of this study was to determine whether the addition of low-dose (renal-dose) dopamine to furosemide therapy enhances natriuresis in patients with compensated congestive heart failure, New York Heart Association Class II or III. We performed a randomized, controlled, open-label, crossover study wherein urinary sodium, creatinine, and furosemide excretion rates and GFR determined by inulin clearance rates were measured during each of three treatment interventions: furosemide infusion alone, dopamine infusion alone, and furosemide and dopamine infusions administered concurrently. Six of eight recruited subjects (4 male, 2 female) were able to complete the study. The baseline sodium excretion rate after equilibration on a metabolic diet was 6.7 +/- 0.7 mEq (mean +/- SE) over 3 h. Infusion of dopamine alone caused a slight nonsignificant increase in natriuresis to 36.7 +/- 8.5 mEq/3 h. Furosemide alone markedly increased sodium excretion to 276.6 +/- 47.2 mEq/3 h. No significant additional increment in natriuresis occurred when dopamine and furosemide were administered concurrently (253.8 +/- 73.6 mEq/3 h). Neither dopamine, furosemide, or their coadministration affected GFR. In conclusion, infusion of low-dose dopamine does not enhance furosemide-induced urinary sodium excretion rates in patients with compensated congestive heart failure, New York Heart Association Class II or III.
The comparative incidence of malignant disease in rheumatoid arthritics exposed to different treatment regimens.
Authors: B L Hazleman
Journal: Annals of the Rheumatic Diseases (1982)

Cytotoxic drugs are effective in disease suppression and affect the immune system. The correlation between these is poor, in many patients, at the dosage used in man. This may partly explain why the large increased risk of neoplasia, initially predicted, has not been shown to follow the use of cytotoxic therapy. The cause of death in patients with rheumatoid arthritis has been assessed both by surveys based on clinical populations and by reviews of necropsy records. There have been few attempts to assess the influence of drug therapy on mortality, or on the incidence of neoplasia. In addition, evidence is accumulating to suggest that lymphoreticular tumours may be associated with autoimmune disease. There have now been several long-term studies of patients with rheumatoid arthritis treated with immunosuppressives; azathioprine and cyclophosphamide in particular. These studies are reviewed and it is concluded that the incidence of most of the common cancers is not increased.
Some aspects of respiratory function in three siblings with Morquio-Brailsford disease
Authors: E. O. S. Hope, M. J. B. Farebrother, D. Bainbridge
Journal: Thorax (1973)

Morquio-Brailsford disease is a rare genetic disorder of mucopolysaccharide metabolism, and its features include dwarfism and thoracic deformity. A boy aged 15 with this condition developed respiratory failure and later died. This boy and his two affected female siblings were studied and the results are presented. The height of the lungs was less than the anteroposterior diameter on standard chest radiographs. All had small lungs without evidence of airways obstruction. Measurements of dependent airway closure were made in the erect and supine positions. These showed some abnormalities which could cause ventilation-perfusion imbalance. Possible mechanisms leading to the development of respiratory failure in this condition are discussed, including nasopharyngeal obstruction, thoracic deformity, and disturbed ventilation-perfusion relationships. The importance of respiratory failure as a cause of death in Morquio9s disease is emphasized.
ESCRT-mediated Uptake and Degradation of Brain-targeted α-synuclein Single Chain Antibody Attenuates Neuronal Degeneration In Vivo
Authors: Brian Spencer, Sharareh Emadi, Paula Desplats, Simona Eleuteri, Sarah Michael, Kori Kosberg, Jay Shen, Edward Rockenstein, Christina Patrick, Anthony Adame, Tania Gonzalez, Michael Sierks, Eliezer Masliah
Journal: Molecular Therapy (2014)

Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species of α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed by Fc receptors. For this study, we investigated an scFV directed against oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B (apoB). The modified scFV showed enhanced brain penetration and was imported into neuronal cells through the endosomal sorting complex required for transport (ESCRT) pathway, leading to lysosomal degradation of α-syn aggregates. Further analysis showed that the scFV was effective at ameliorating neurodegenerative pathology and behavioral deficits observed in the mouse model of dementia with Lewy bodies/Parkinson's disease. Thus, the apoB modification had the effect of both increasing accumulation of the scFV in the brain and directing scFV/α-syn complexes for degradation through the ESCRT pathway, leading to improved therapeutic potential of immunotherapy. Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species of α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed by Fc receptors. For this study, we investigated an scFV directed against oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B (apoB). The modified scFV showed enhanced brain penetration and was imported into neuronal cells through the endosomal sorting complex required for transport (ESCRT) pathway, leading to lysosomal degradation of α-syn aggregates. Further analysis showed that the scFV was effective at ameliorating neurodegenerative pathology and behavioral deficits observed in the mouse model of dementia with Lewy bodies/Parkinson's disease. Thus, the apoB modification had the effect of both increasing accumulation of the scFV in the brain and directing scFV/α-syn complexes for degradation through the ESCRT pathway, leading to improved therapeutic potential of immunotherapy.
A review of outcomes of indwelling pleural catheters (IPC) for malignant pleural effusions (MPE) at the Cambridge Pleural unit UK
Authors: Thomas Pulimood, Sumit Chatterji, Elaine Reid, Pasupathy Sivasothy
Journal: European Respiratory Journal (2013)

Introduction: IPCs are used in breathless patients with malignant pleural effusions (MPE). Methods: A descriptive study of 131 Rocket® IPC insertions in our tertiary unit between April 2009 and February 2013. Patients had MPE with expected survival > 1 month. Drains inserted by ultrasound guidance and local anaesthetic using standard technique. Results: 131 patients. Mean age 70. Diagnoses see table 1. Indications - 61 patients had trapped lung, 34 high output effusions, 32 failed pleurodesis, 1 drain reinserted for a fractured tip and 2 for patient preference. 20 patients auto-pleurodesed. All of these had the drain removed successfully. Those who had IPC's removed drained for an average of 87 days. Those who died before IPC removal, drained for an average of 73 days. No recorded pleural infection. 11 had minor complications – local cellulitis (3), insertion site discomfort (2), blocked drain (1), dislodged drain (1) faulty leaking cap (1) and loculated space (3). Discussion: IPCs can effectively manage MPE’s due to a variety of cancers with little complication. We use doxycycline 100mg orally for 7 days post-insertion to prevent early pleural space infection. This is relevant to this group of patients who have palliative chemotherapy. Being a referral centre, our elective patients are often admitted overnight, but this procedure can be safely done as a day case and should be offered as an alternative in selected patient groups with the described indications.

View this table:

Table1: Frequency distribution of the malignant diagnosis.
<i>MDM2</i> Promoter SNP309 Is Associated with Risk of Occurrence and Advanced Lymph Node Metastasis of Nasopharyngeal Carcinoma in Chinese Population
Authors: Gangqiao Zhou, Yun Zhai, Ying Cui, Xiumei Zhang, Xiaojia Dong, Hao Yang, Ying He, Kaitai Yao, Hongxing Zhang, Lianteng Zhi, Xiaoyan Yuan, Wei Qiu, Xiaoai Zhang, Yan Shen, Boqing Qiang, Fuchu He
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Mouse double minute 2 (MDM2) is a key negative regulator of the p53 activity. Recently, a polymorphism in the MDM2 intronic promoter, SNP309, was shown to influence MDM2 expression and p53 activity. We examined whether the SNP309 was related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. Experimental Design: We genotyped the SNP309 in two independent case-control populations in southern China, one is from Guangxi province (including 593 NPC patients and 480 controls) and the other is from Guangdong province (including 239 patients and 286 controls), by PCR direct sequencing. Multivariate logistic regression analysis was used to calculate adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results: We observed that compared with the TT genotype, the genotypes containing G allele (GT + GG genotype) were associated with significant increased susceptibility to NPC in both Guangxi (OR, 1.43; 95% CI, 1.04-1.91) and Guangdong population (OR, 1.53; 95% CI, 1.00-2.36). When these two sample sets were combined, the OR of the GT + GG genotype developing NPC was 1.45 (95% CI, 1.12-1.85) compared with the TT genotype. Furthermore, compared with the TT genotype, the GT + GG genotype was also significantly associated with the advanced lymph node metastasis (OR, 1.84; 95% CI, 1.09-3.05). Conclusions: Our findings suggest that the MDM2 SNP309 may be a risk factor for the occurrence and advanced neck lymph node metastasis of NPC in Chinese population.
Osteoprotegerin Reverses Osteoporosis by Inhibiting Endosteal Osteoclasts and Prevents Vascular Calcification by Blocking a Process Resembling Osteoclastogenesis
Authors: Hosung Min, Sean Morony, Ildiko Sarosi, Colin R. Dunstan, Casey Capparelli, Sheila Scully, Gwyneth Van, Steve Kaufman, Paul J. Kostenuik, David L. Lacey, William J. Boyle, W. Scott Simonet
Journal: The Journal of Experimental Medicine (2000)

High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause osteopetrosis with normal tooth eruption and bone elongation and inhibit the development and activity of endosteal, but not periosteal, osteoclasts. We demonstrate that both intravenous injection of recombinant OPG protein and transgenic overexpression of OPG in OPG(-/-) mice effectively rescue the osteoporotic bone phenotype observed in OPG-deficient mice. However, intravenous injection of recombinant OPG over a 4-wk period could not reverse the arterial calcification observed in OPG(-/-) mice. In contrast, transgenic OPG delivered from mid-gestation through adulthood does prevent the formation of arterial calcification in OPG(-/-) mice. Although OPG is normally expressed in arteries, OPG ligand (OPGL) and receptor activator of NF-kappaB (RANK) are not detected in the arterial walls of wild-type adult mice. Interestingly, OPGL and RANK transcripts are detected in the calcified arteries of OPG(-/-) mice. Furthermore, RANK transcript expression coincides with the presence of multinuclear osteoclast-like cells. These findings indicate that the OPG/OPGL/RANK signaling pathway may play an important role in both pathological and physiological calcification processes. Such findings may also explain the observed high clinical incidence of vascular calcification in the osteoporotic patient population.
Gender differences in ventricular arrhythmia recurrence in patients with coronary artery disease and implantable cardioverter-defibrillators
Authors: Rachel Lampert, Craig A. McPherson, Jude F. Clancy, Teresa L. Caulin-Glaser, Lynda E. Rosenfeld, William P. Batsford
Journal: Journal of the American College of Cardiology (2004)
Creeping eruption caused by a larva of the suborder Spirurina type X
Authors: None Goto, None Tamura, None Ishikawa, None Miyachi, None Ishii, None Akao
Journal: British Journal of Dermatology (1998)

Journal Article Creeping eruption caused by a larva of the suborder Spirurina type X Get access Y. Goto, Y. Goto Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan, Dr YaeGoto E‐mail: ygoto@sb.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar A. Tamura, A. Tamura Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan, Search for other works by this author on: Oxford Academic Google Scholar O. Ishikawa, O. Ishikawa Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan, Search for other works by this author on: Oxford Academic Google Scholar Y. Miyachi, Y. Miyachi Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan, Search for other works by this author on: Oxford Academic Google Scholar T. Ishii, T. Ishii Kurosawa Hospital, Takasaki, Japan, Search for other works by this author on: Oxford Academic Google Scholar N. Akao N. Akao Department of Medical Zoology, Tokyo Medical and Dental University School of Medicine, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 139, Issue 2, 1 August 1998, Pages 315–318, https://doi.org/10.1046/j.1365-2133.1998.02375.x Published: 01 August 1998
The Roles of mTOR Complexes in Lipid Metabolism
Authors: Alexandre Caron, Denis Richard, Mathieu Laplante
Journal: Annual Review of Nutrition (2015)

The synthesis of lipids in response to food intake represents a key advantage that allows organisms to survive when energy availability is limited. In mammals, circulating levels of insulin and nutrients, which fluctuate between fasting and feeding, dictate whether lipids are synthesized or catabolized by tissues. The mechanistic target of rapamycin (mTOR), a kinase that is activated by anabolic signals, plays fundamental roles in regulating lipid biosynthesis and metabolism in response to nutrition. The mTOR kinase nucleates two large protein complexes named mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Following their activation, these complexes facilitate the accumulation of triglycerides by promoting adipogenesis and lipogenesis and by shutting down catabolic processes such as lipolysis and β-oxidation. Here, we review and discuss the roles of mTOR complexes in various aspects of lipid metabolism in mammals. We also use this opportunity to discuss the implication of these relations to the maintenance of systemic lipid homeostasis.
STRONTIUM AND ITS RELATION TO CALCIUM METABOLISM*
Authors: F. Bronner, J.-P. Aubert, L. J. Richelle, P. D. Saville, J. A. Nicholas, J. R. Cobb
Journal: Journal of Clinical Investigation (1963)

Interest in strontium and its relation to cal- cium metabolism dates back over 20 years.At that time, radioactive calcium (Car) was rela- tively unavailable.It was thought that radio- active strontium (Srr), which was more readily available and which can be detected more simply, might serve as a substitute tracer for Car.Early experiments (1-3) confirmed this notion in a general way, and several investigators (4-7) have subsequently proceeded on the assumption that Sr behaves like Ca in the body.Although the urinary excretions of Sr and Ca were found to differ, it has been assumed or demonstrated that as far as the skeleton is concerned, differences in the biological behavior of Ca and Sr are small and perhaps negligible (4, 8-15).Intrinsic interest in Sr was heightened when it was found to be an important product of fallout resulting from the explosion of nuclear devices in the atmosphere.Protection against Sr fall- out depends on adequate knowledge of the me- tabolism of this nuclide, and in the last decade, a large number of studies have been published that deal with various aspects of Sr metabolism (16).Clinical interest in Sr developed when Shorr and Carter (17) proposed treating patients with postmenopausal osteoporosis by giving them Sr supplements in the diet (18).Sr rickets has been known since the early work of Lehnerdt (19, 20) and has been studied subsequently (21).To use Sr as a tracer for Ca requires detailed knowledge of the metabolism of these elements.Knowledge of Ca metabolism has progressed considerably in recent years, so that a formal analysis of the metabolic behavior of this element
Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2.
Authors: H Sheng, J Shao, S C Kirkland, P Isakson, R J Coffey, J Morrow, R D Beauchamp, R N DuBois
Journal: Journal of Clinical Investigation (1997)

A considerable amount of evidence collected from several different experimental systems indicates that cyclooxygenase-2 (COX-2) may play a role in colorectal tumorigenesis. Large epidemiologic studies have shown a 40-50% reduction in mortality from colorectal cancer in persons taking aspirin or other nonsteroidal antiinflammatory drugs on a regular basis. One property shared by all of these drugs is their ability to inhibit COX, a key enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX have been characterized, COX-1 and COX-2. COX-2 is expressed at high levels in intestinal tumors in humans and rodents. In this study, we selected two transformed human colon cancer cell lines for studies on the role of COX-2 in intestinal tumorigenesis. We evaluated HCA-7 cells which express high levels of COX-2 protein constitutively and HCT-116 cells which lack COX-2 protein. Treatment of nude mice implanted with HCA-7 cells with a selective COX-2 inhibitor (SC-58125), reduced tumor formation by 85-90%. SC-58125 also inhibited colony formation of cultured HCA-7 cells. Conversely, SC-58125 had no effect on HCT-116 implants in nude mice or colony formation in culture. Here we provide evidence that there may be a direct link between inhibition of intestinal cancer growth and selective inhibition of the COX-2 pathway.
The expression of ob gene is not acutely regulated by insulin and fasting in human abdominal subcutaneous adipose tissue.
Authors: H Vidal, D Auboeuf, P De Vos, B Staels, J P Riou, J Auwerx, M Laville
Journal: Journal of Clinical Investigation (1996)

The regulation of ob gene expression in abdominal subcutaneous adipose tissue was investigated using a reverse transcription-competitive PCR method to quantify the mRNA level of leptin. Leptin mRNA level was highly correlated with the body mass index of 26 subjects (12 lean, 7 non-insulin-dependent diabetic, and 7 obese patients). The effect of fasting on ob gene expression was investigated in 10 subjects maintained on a hypocaloric diet (1045 KJ/d) for 5 d. While their metabolic parameters significantly changed (decrease in insulinemia, glycemia, and resting metabolic rate and increase in plasma ketone bodies), the caloric restriction did not modify the leptin mRNA level in the adipose tissue. To verify whether insulin regulates ob gene expression, six lean subjects underwent a 3-h euglycemic hyperinsulinemic (846 +/- 138 pmol/liter) clamp. Leptin and Glut 4 mRNA levels were quantified in adipose tissue biopsies taken before and at the end of the clamp. Insulin infusion produced a significant threefold increase in Glut 4 mRNA while leptin mRNA was not affected. It is concluded that ob gene expression is not acutely regulated by insulin or by metabolic factors related to fasting in human abdominal subcutaneous adipose tissue.
Behcet's disease with life-threatening haemoptoe and pulmonary aneurysms: complete remission after infliximab treatment
Authors: K Baki, P M Villiger, D Jenni, T Meyer, J H Beer
Journal: Annals of the Rheumatic Diseases (2006)

A 25-year-old man was admitted to our hospital because of life-threatening haemoptoe and haematemesis. Recurring painful oral and genital aphtae and an episode of epididymitis led to a diagnosis of Behcet’s disease 18 months earlier.1 Treatment with colchicine (1 mg/day) and prednisone (50 mg/day) was started, with a rapid tapering of prednisone. Intermittent fever and a cardiac murmur led to the suspicion of endocarditis 6 months later. Transoesophageal echocardiography disclosed a right ventricular cardiac thrombus of 4 cm diameter. The clinical investigation did not show signs of vasculitis nor could a thrombophilia be diagnosed. Oral anticoagulation was initiated and continued until complete resolution of the cardiac thrombus. Azathioprine (75 mg/day) was prescribed in combination with prednisone (75 mg/day), with the recommendation …
Transforming growth factor beta 1 selectively regulates early murine hematopoietic progenitors and inhibits the growth of IL-3-dependent myeloid leukemia cell lines.
Authors: J R Keller, C Mantel, G K Sing, L R Ellingsworth, S K Ruscetti, F W Ruscetti
Journal: The Journal of Experimental Medicine (1988)

Transforming growth factor beta 1 (TGF-beta 1) has been shown to be associated with active centers of hematopoiesis and lymphopoiesis in the developing fetus. Therefore, the effects of TGF-beta 1 on mouse hematopoiesis were studied. TGF-beta 1 is a potent inhibitor of IL-3-induced bone marrow proliferation, but it does not inhibit the proliferation induced by granulocyte/macrophage, colony-stimulating factor (CSF), granulocyte CSF, and erythropoietin (Epo). TGF-beta 1 also inhibits IL-3-induced multipotential colony formation of bone marrow cells in soft agar, which includes early erythroid differentiation, while Epo-induced terminal differentiation is unaffected. In addition, IL-3-induced granulocyte/macrophage colonies were inhibited; however, small clusters of differentiated myeloid cells were consistently seen in cultures containing IL-3 and TGF-beta 1. Thus, TGF-beta 1 selectively inhibits early hematopoietic progenitor growth and differentiation but not more mature progenitors. TGF-beta 1 is also a potent inhibitor of IL-3-dependent and -independent myelomonocytic leukemic cell growth, while the more mature erythroid and macrophage leukemias are insensitive. Therefore, TGF-beta 1 functions as a selective regulator of differentiating normal hematopoietic cells, and suppresses myeloid leukemic cell growth.