tbuckley/cabot-search huggingface dataset:
Effects of norepinephrine and angiotensin II on the determinants of glomerular ultrafiltration and proximal tubule fluid reabsorption in the rat.
Authors: B D Myers, W M Deen, B M Brenner
Journal: Circulation Research (1975)

In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both hormones produced elevations in single nephron filtration fraction due to declines in glomerular plasma flow with little change in nephron glomerular filtration rate. The resulting large increases in the efferent arteriolar oncotic pressure, piE, were accompanied by equivalent increases in the mean glomerular transcapillary hydraulic pressure difference, deltaP. Equality of piE and deltaP, denoting filtration pressure equilibrium, obtained before and during infusion of either hormone. Por both hormones, when elevations in AP were allowed, marked and roughly proportional increases in the resistance to blood flow through single afferent and efferent arterioles occurred, whereas when increases in AP were prevented by partial aortic constriction increases in resistance were confined primarily to the efferent arteriole. Tespite the marked increases in piE, absolute rates of proximal tubule fluid reabsorption, on the average, were unchanged by these hormones due to the opposing effects of marked decreases in efferent arteriolar plasma flow rate and, to a lesser extent, increases in peritubular capillary hydraulic pressure.
Second-hand smoke exposure in cars and respiratory health effects in children
Authors: Z. Kabir, P. J. Manning, J. Holohan, S. Keogan, P. G. Goodman, L. Clancy
Journal: European Respiratory Journal (2009)

We examined potential associations of ever asthma, and symptoms of wheeze (past 12 months), hay fever, eczema and bronchitis (cough with phlegm) among school children exposed to second-hand smoke (SHS) in cars, using a modified Irish International Study of Asthma and Allergies in Childhood (ISAAC) protocol. 2,809 children of 13–14 yrs old and who selected randomly from post-primary schools throughout Ireland completed the 2007 ISAAC self-administered questionnaire. Adjusted OR (adjusted for sex, active smoking status of children interviewed and their SHS exposure at home) were estimated for the associations studied, using multivariable logistic regression techniques. Overall, 14.8% (13.9% in young males, 15.4% in young females) of Irish children aged 13–14 yrs old were exposed to SHS in cars. Although there was a tendency towards increased likelihood of both respiratory and allergic symptoms with SHS exposure in cars, wheeze and hay fever symptoms were significantly higher (adjusted OR 1.35 (95% CI 1.08–1.70) and 1.30 (1.01–1.67), respectively), while bronchitis symptoms and asthma were not significant (1.33 (0.92–1.95) and 1.07 (0.81–1.42), respectively). Approximately one in seven Irish schoolchildren are exposed to SHS in cars and could have adverse respiratory health effects. Further studies are imperative to explore such associations across different population settings.
Glossopharyngeal Neuralgia Associated with Bradycardia, Syncope, and Seizures
Authors: YIHONG KONG, ALBERT HEYMAN, MARK L. ENTMAN, HENRY D. MCINTOSH
Journal: Circulation (1964)

An unusual case of glossopharyngeal neuralgia associated with bradycardia, hypotension, syncope, and seizure is described. Our observations indicate that the cardiovascular components of this syndrome are probably due to stimulation of vagal centers by pain impulses arising from the glossopharyngeal area. Diphenylhydantoin therapy produced satisfactory relief of symptoms in this patient, probably by modification of the intensity of the neuralgic pain and thereby reducing the central vagal response.
Palliative Care = Hope
Authors: Kenneth E. Covinsky
Journal: JAMA Internal Medicine (2013)

This poignant case illustrates some of the barriers to appropriate engagement of a palliative care team.The emergency medicine physician mistakenly equated palliative care with giving up hope.However, hope is not lost when we approach the limits of medical science's capacity to cure disease and prolong life.Rather, that is the time we can give hope to the patient and family through palliative care, which focuses on quality-of-life needs, symptom control, psychological support, and caregiver support.Palliative care would have been an opportunity to offer comfort and hope to Bonnie and her family.A palliative care team would have been comfortable with and sensitive to the
Mutation Status of the Residual <i>ATM</i> Allele Is an Important Determinant of the Cellular Response to Chemotherapy and Survival in Patients With Chronic Lymphocytic Leukemia Containing an 11q Deletion
Authors: Belinda Austen, Anna Skowronska, Claire Baker, Judith E. Powell, Anne Gardiner, David Oscier, Aneela Majid, Martin Dyer, Reiner Siebert, A. Malcolm Taylor, Paul A. Moss, Tatjana Stankovic
Journal: Journal of Clinical Oncology (2007)

The ataxia telangiectasia mutated (ATM) gene is located on chromosome 11q and loss of this region is common in B-cell chronic lymphocytic leukemia (CLL). Our aim was to determine if CLL tumors with a chromosome 11q deletion might be divided into two subgroups based on the status of the remaining ATM allele.The sequence of the residual ATM allele was determined in 72 CLLs with an 11q deletion. This was related to the cellular response to irradiation or cytotoxic drug exposure in vitro and clinical outcome.We show that the residual ATM allele is mutated in 36% of CLLs with an 11q deletion and that these leukemias demonstrate an impaired cellular response to irradiation or cytotoxic drug exposure in vitro. Inactivation of the second ATM allele was associated with a reduction in patient survival beyond that already dictated by the presence of an 11q deletion (P = .0283). Furthermore, we demonstrate that ATM mutations may arise during the evolution of an 11q deleted subclone and are associated with its expansion.CLL with 11q deletion can be divided into two subgroups based on the integrity of the residual ATM allele. Patients with complete loss of ATM function, due to biallelic ATM defects, have defective responses to cytotoxic chemotherapeutics in vitro and a poorer clinical outcome. ATM mutant subclones can develop during an individual's disease course and give rise to additional expansion of the 11q deleted subclone.
Cost Analysis of Human Islet Transplantation for the Treatment of Type 1 Diabetes in the Swiss-French Consortium GRAGIL
Authors: Adrienne P. Guignard, José Oberholzer, Pierre-Yves Benhamou, Sandrine Touzet, Pascal Bucher, Alfred Penfornis, François Bayle, Laurence Kessler, Charles Thivolet, Lionel Badet, Philippe Morel, Cyril Colin
Journal: Diabetes Care (2004)

OBJECTIVE—To evaluate the cost of islet transplantation in type 1 diabetic patients with a functional renal graft in a multicenter network. RESEARCH DESIGN AND METHODS—The study involved nine diabetic patients transplanted in the Swiss-French Groupe Rhône-Alpes, Rhin et Geneve pour la transplantation d’Ilots Langerhans (GRAGIL) consortium between March 1999 and June 2000. The direct medical costs were estimated from Social Security’s perspective from the inclusion of the patient to 1 year after transplantation. All cost components were computed separately and included evaluation, screening and candidacy, organ retrieval, islet processing, pancreas and islet transportation, hospitalization for transplantation, follow-up, medications (immunosuppressive, antidiabetic, and adjuvant drugs), and adverse events requiring hospitalization. RESULTS—During the study period, 56 pancreata were processed and 14 islet preparations were transplanted. The average cost of an islet transplantation (procedure and 1-year follow-up) was €77,745 (French rate, year 2000). The four main cost components were islet preparation (30% of the total cost), adverse events (24%), drugs (14%), and hospitalization (13%). CONCLUSIONS—Overall costs of islet transplantation are slightly higher than those of pancreas transplantation. The cell isolation process is a critical point; a reduction in overall cost will require more efficient ways of isolating high yields of viable islets. Costs generated by shipments within the GRAGIL network did not represent an economic burden. It can be expected that the costs will decrease with growing experience and improving technology.
Erosive hand osteoarthritis: its prevalence and clinical impact in the general population and symptomatic hand osteoarthritis
Authors: W. Y. Kwok, M. Kloppenburg, F. R. Rosendaal, J. B. van Meurs, A. Hofman, S. M. A. Bierma-Zeinstra
Journal: Annals of the Rheumatic Diseases (2011)

To estimate the prevalence of erosive hand osteoarthritis (EOA) in the general population and its relation to symptomatic hand osteoarthritis (HOA), hand pain and disability.Baseline data of participants from a population-based study (age ≥55 years) were used. Symptomatic HOA was defined as hand pain and in addition to radiographic HOA (at least one interphalangeal (IP) joint or 1st carpometacarpal joint with Kellgren-Lawrence grade ≥2). EOA was defined as having at least one IP joint with erosions according to the Verbruggen-Veys scoring method. Hand pain and disability were self-reported. Multivariate logistic regression analyses were used to estimate the effect of EOA on pain and disability. Results were presented as OR with a 95% CI, adjusted for age and sex.Of 3430 participants, radiographic HOA was seen in 56% (n=1916) and symptomatic HOA in 11% (n=371). Erosions were seen in 96 subjects. The prevalence of EOA in the general, radiographic and symptomatic HOA population was 2.8%, 5.0% and 10.2%, respectively. Presence of EOA led to adjusted ORs for pain of 3.6 (95% CI 2.4 to 5.6) and for disability 2.4 (95% CI 1.1 to 5.4). In radiographic HOA, people with erosion(s) had more hand pain (adjusted OR=3.1, 95% CI 2.0 to 4.8) or disability (adjusted OR=2.5, 95% CI 1.1 to 5.8) than people without erosion(s).The prevalence of EOA is 2.8% in the general population and 10.2% in individuals with symptomatic HOA. It has a substantial impact on hand pain and disability.
Uremic Cardiomyopathy and Insulin Resistance
Authors: David Semple, Katie Smith, Sunil Bhandari, Anne-Marie L. Seymour
Journal: Journal of the American Society of Nephrology (2010)

Uremic cardiomyopathy is a classic complication of chronic renal failure whose cause is unclear and treatment remains disappointing. Insulin resistance is an independent predictor of cardiovascular mortality in chronic renal failure. Underlying insulin resistance are defects in insulin signaling through the protein kinase, Akt. Akt acts as a nodal point in the control of both the metabolic and pleiotropic effects of insulin. Imbalance among these effects leads to cardiac hypertrophy, fibrosis, and apoptosis; less angiogenesis; metabolic remodeling; and altered calcium cycling, all key features of uremic cardiomyopathy. Here we consider the role of Akt in the development of uremic cardiomyopathy, drawing parallels from models of hypertrophic cardiac disease.
Antiquity and Evolution of the MADS-Box Gene Family Controlling Flower Development in Plants
Authors: J. Nam
Journal: Molecular Biology and Evolution (2003)

MADS-box genes in plants control various aspects of development and reproductive processes including flower formation. To obtain some insight into the roles of these genes in morphological evolution, we investigated the origin and diversification of floral MADS-box genes by conducting molecular evolutionary genetics analyses. Our results suggest that the most recent common ancestor of today's floral MADS-box genes evolved roughly 650 MYA, much earlier than the Cambrian explosion. They also suggest that the functional classes T (SVP), B (and Bs), C, F (AGL20 or TM3), A, and G (AGL6) of floral MADS-box genes diverged sequentially in this order from the class E gene lineage. The divergence between the class G and E genes apparently occurred around the time of the angiosperm/gymnosperm split. Furthermore, the ancestors of three classes of genes (class T genes, class B/Bs genes, and the common ancestor of the other classes of genes) might have existed at the time of the Cambrian explosion. We also conducted a phylogenetic analysis of MADS-domain sequences from various species of plants and animals and presented a hypothetical scenario of the evolution of MADS-box genes in plants and animals, taking into account paleontological information. Our study supports the idea that there are two main evolutionary lineages (type I and type II) of MADS-box genes in plants and animals.
Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study
Authors: Caroline Brand, J Snaddon, Michael Bailey, Flavia M Cicuttini
Journal: Annals of the Rheumatic Diseases (2001)

There is a putative role for antioxidant treatment in osteoarthritis (OA) based on animal, epidemiological, and human clinical studies. Vitamin E, a fat soluble vitamin, is one of the major dietary antioxidants. Short term clinical studies using vitamin E in the form of alpha-tocopherol suggested a benefit over placebo of similar dimension to that of diclofenac for relief of OA pain.A six month, double blind, randomised, placebo controlled study of vitamin E 500 IU/day was carried out. Primary outcome measures were pain, stiffness, and function. Statistical analysis was performed on an intention to treat basis.77 patients were included in the study. Vitamin E showed no benefit over placebo at one month, three months, or six months for any of the outcome measures. The placebo group had higher pain levels (p=0.15) and body mass index (p=0.03) at baseline, and lower pain levels (p=0.02) at completion of the study. Radiological score, exercise score, age, or antioxidant intake at baseline or six months did not differ between the groups. The reasons for the better performance of the placebo group are uncertain but may relate to the initially higher pain score and subsequent regression to the mean.Vitamin E shows no benefit for the management of symptomatic knee OA. The role of vitamin E in preventing OA progression is currently under investigation.
Enhancement of electrogenic Na+ transport across rat inner medullary collecting duct by glucocorticoid and by mineralocorticoid hormones.
Authors: R F Husted, J R Laplace, J B Stokes
Journal: Journal of Clinical Investigation (1990)

We have investigated the effect of steroid hormones on Na+ transport by rat renal inner medullary collecting duct (IMCD) cells. These cells, grown on permeable supports in primary culture, grow to confluence and develop a transmonolayer voltage oriented such that the apical surface is negative with respect to the basal surface. The results of these experiments demonstrate that this voltage is predominantly (or exclusively) the result of electrogenic Na+ absorption. Na+ transport can be stimulated two- to fourfold by exposure to either dexamethasone or aldosterone (100 nM). Experiments using specific antagonists of the glucocorticoid and mineralocorticoid receptors indicate that activation of either receptor stimulates electrogenic Na+ transport; electroneutral Na+ transport is undetectable. Two other features of the IMCD emerge from these studies. (a) These cells appear to have the capacity to metabolize the naturally occurring glucocorticoid hormone corticosterone. (b) The capacity for K+ secretion is minimal and steroid hormones do not induce or stimulate conductive K+ secretion as they do in the cortical collecting duct.
Effect of Adrenalectomy on the Renal Response to Chloride Depletion in the Rat
Authors: R. G. Luke
Journal: Journal of Clinical Investigation (1974)

These experiments were aimed at investigating renal behavior towards chloride, as distinct from sodium, during dietary deprivation of these ions in adrenalectomized rats. Adrenalectomized and shamoperated control rats were maintained on saline for 3 wk, then chloride conservation during a very low chloride intake was assessed both with an abundant sodium intake (as buffered sodium phosphate in the drinking water) and after subsequent withdrawal of sodium. When sodium intake was high, there was no difference in chloride conservation between adrenalectomized and control animals, and sodium balance and weight were maintained similarly in both groups. At the same time, both experimental and control rats developed significant hypokalemia and elevation of the plasma bicarbonate levels as compared to other control rats ingesting a normal diet. In another group of adrenalectomized rats sodium phosphate was withdrawn, after normal chloride conservation was observed, and the low-salt diet continued. Negative sodium balance developed and was associated with a negative chloride balance, whereas sham-operated rats continued to conserve sodium and chloride. In further studies during polyuria, both adrenalectomized and control rats developed urinary chloride concentrations of less than 1 meq/liter.
The aetiology, origins, and diagnosis of severe acute respiratory syndrome
Authors: LLM Poon, Y Guan, JM Nicholls, KY Yuen, JSM Peiris
Journal: The Lancet Infectious Diseases (2004)

Severe acute respiratory syndrome (SARS) is a new infectious disease that first emerged in Guangdong province, China, in November, 2002. A novel coronavirus was later identified in patients with SARS. The detection of the virus in these patients, its absence in healthy controls or other patients with atypical pneumonia, and the reproduction of a similar disease in a relevant animal model fulfilled Koch's postulates for implicating this coronavirus as the causal agent of SARS. The full genome sequence was determined within weeks of the virus's identification. The rapid progress in the aetiology, the development of laboratory diagnostic tests, and the defining of routes of viral transmission were facilitated through a unique WHO-coordinated virtual network of laboratories, which shared information on a real-time basis through daily teleconferences. Subsequent studies have indicated that the SARS coronavirus is of animal origin, that its precursor is still present in animal populations within the region, and that live-animal markets in southern China may have provided the animal-human interphase that allowed this precursor virus to adapt to human-human transmission. These findings underscore the potential for the re-emergence of SARS and the need for laboratory tests for early diagnosis. However, the low viral load in the respiratory tract makes early diagnosis of SARS a diagnostic challenge, although improvements in the sensitivity of molecular diagnostic methods continue to be made.
Evolution of Substrate Specificity in a Recipient’s Enzyme Following Horizontal Gene Transfer
Authors: Lianet Noda-García, Aldo R. Camacho-Zarco, Sofía Medina-Ruíz, Paul Gaytán, Mauricio Carrillo-Tripp, Vilmos Fülöp, Francisco Barona-Gómez
Journal: Molecular Biology and Evolution (2013)

Despite the prominent role of horizontal gene transfer (HGT) in shaping bacterial metabolism, little is known about the impact of HGT on the evolution of enzyme function. Specifically, what is the influence of a recently acquired gene on the function of an existing gene? For example, certain members of the genus Corynebacterium have horizontally acquired a whole l-tryptophan biosynthetic operon, whereas in certain closely related actinobacteria, for example, Mycobacterium, the trpF gene is missing. In Mycobacterium, the function of the trpF gene is performed by a dual-substrate (βα)8 phosphoribosyl isomerase (priA gene) also involved in l-histidine (hisA gene) biosynthesis. We investigated the effect of a HGT-acquired TrpF enzyme upon PriA's substrate specificity in Corynebacterium through comparative genomics and phylogenetic reconstructions. After comprehensive in vivo and enzyme kinetic analyses of selected PriA homologs, a novel (βα)8 isomerase subfamily with a specialized function in l-histidine biosynthesis, termed subHisA, was confirmed. X-ray crystallography was used to reveal active-site mutations in subHisA important for narrowing of substrate specificity, which when mutated to the naturally occurring amino acid in PriA led to gain of function. Moreover, in silico molecular dynamic analyses demonstrated that the narrowing of substrate specificity of subHisA is concomitant with loss of ancestral protein conformational states. Our results show the importance of HGT in shaping enzyme evolution and metabolism.
Lack of Effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation
Authors: David J. Margolis, Jayanta Gupta, Ole Hoffstad, Maryte Papdopoulos, Henry A. Glick, Stephen R. Thom, Nandita Mitra
Journal: Diabetes Care (2013)

OBJECTIVE Hyperbaric oxygen (HBO) is a device that is used to treat foot ulcers. The study goal was to compare the effectiveness of HBO with other conventional therapies administered in a wound care network for the treatment of a diabetic foot ulcer and prevention of lower-extremity amputation. RESEARCH DESIGN AND METHODS This was a longitudinal observational cohort study. To address treatment selection bias, we used propensity scores to determine the “propensity” that an individual was selected to receive HBO. RESULTS We studied 6,259 individuals with diabetes, adequate lower limb arterial perfusion, and foot ulcer extending through the dermis, representing 767,060 person-days of wound care. In the propensity score–adjusted models, individuals receiving HBO were less likely to have healing of their foot ulcer (hazard ratio 0.68 [95% CI 0.63–0.73]) and more likely to have an amputation (2.37 [1.84–3.04]). Additional analyses, including the use of an instrumental variable, were conducted to assess the robustness of our results to unmeasured confounding. HBO was not found to improve the likelihood that a wound might heal or to decrease the likelihood of amputation in any of these analyses. CONCLUSIONS Use of HBO neither improved the likelihood that a wound would heal nor prevented amputation in a cohort of patients defined by Centers for Medicare and Medicaid Services eligibility criteria. The usefulness of HBO in the treatment of diabetic foot ulcers needs to be reevaluated.