tbuckley/cabot-search huggingface dataset:
The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose.
Authors: Y Kanai, W S Lee, G You, D Brown, M A Hediger
Journal: Journal of Clinical Investigation (1994)

The major reabsorptive mechanism for D-glucose in the kidney is known to involve a low affinity high capacity Na+/glucose cotransporter, which is located in the early proximal convoluted tubule segment S1, and which has a Na+ to glucose coupling ratio of 1:1. Here we provide the first molecular evidence for this renal D-glucose reabsorptive mechanism. We report the characterization of a previously cloned human kidney cDNA that codes for a protein with 59% identity to the high affinity Na+/glucose cotransporter (SGLT1). Using expression studies with Xenopus laevis oocytes we demonstrate that this protein (termed SGLT2) mediates saturable Na(+)-dependent and phlorizin-sensitive transport of D-glucose and alpha-methyl-D-glucopyranoside (alpha MeGlc) with Km values of 1.6 mM for alpha MeGlc and approximately 250 to 300 mM for Na+, consistent with low affinity Na+/glucose cotransport. In contrast to SGLT1, SGLT2 does not transport D-galactose. By comparing the initial rate of [14C]-alpha MeGlc uptake with the Na(+)-influx calculated from alpha MeGlc-evoked inward currents, we show that the Na+ to glucose coupling ratio of SGLT2 is 1:1. Using combined in situ hybridization and immunocytochemistry with tubule segment specific marker antibodies, we demonstrate an extremely high level of SGLT2 message in proximal tubule S1 segments. This level of expression was also evident on Northern blots and likely confers the high capacity of this glucose transport system. We conclude that SGLT2 has properties characteristic of the renal low affinity high capacity Na+/glucose cotransporter as previously reported for perfused tubule preparations and brush border membrane vesicles. Knowledge of the structural and functional properties of this major renal Na+/glucose reabsorptive mechanism will advance our understanding of the pathophysiology of renal diseases such as familial renal glycosuria and diabetic renal disorders.
Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials
Authors: Paul E Sax, David Wohl, Michael T Yin, Frank Post, Edwin DeJesus, Michael Saag, Anton Pozniak, Melanie Thompson, Daniel Podzamczer, Jean Michel Molina, Shinichi Oka, Ellen Koenig, Benoit Trottier, Jaime Andrade-Villanueva, Gordon Crofoot, Joseph M Custodio, Andrew Plummer, Lijie Zhong, Huyen Cao, Hal Martin, Christian Callebaut, Andrew K Cheng, Marshall W Fordyce, Scott McCallister
Journal: The Lancet (2015)
Cost-Effectiveness of Cervical Cancer Screening With Human Papillomavirus DNA Testing and HPV-16,18 Vaccination
Authors: J. D. Goldhaber-Fiebert, N. K. Stout, J. A. Salomon, K. M. Kuntz, S. J. Goldie
Journal: JNCI Journal of the National Cancer Institute (2008)

The availability of human papillomavirus (HPV) DNA testing and vaccination against HPV types 16 and 18 (HPV-16,18) motivates questions about the cost-effectiveness of cervical cancer prevention in the United States for unvaccinated older women and for girls eligible for vaccination.An empirically calibrated model was used to assess the quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (2004 US dollars per QALY) of screening, vaccination of preadolescent girls, and vaccination combined with screening. Screening varied by initiation age (18, 21, or 25 years), interval (every 1, 2, 3, or 5 years), and test (HPV DNA testing of cervical specimens or cytologic evaluation of cervical cells with a Pap test). Testing strategies included: 1) cytology followed by HPV DNA testing for equivocal cytologic results (cytology with HPV test triage); 2) HPV DNA testing followed by cytology for positive HPV DNA results (HPV test with cytology triage); and 3) combined HPV DNA testing and cytology. Strategies were permitted to switch once at age 25, 30, or 35 years.For unvaccinated women, triennial cytology with HPV test triage, beginning by age 21 years and switching to HPV testing with cytology triage at age 30 years, cost $78,000 per QALY compared with the next best strategy. For girls vaccinated before age 12 years, this same strategy, beginning at age 25 years and switching at age 35 years, cost $41,000 per QALY with screening every 5 years and $188,000 per QALY screening triennially, each compared with the next best strategy. These strategies were more effective and cost-effective than screening women of all ages with cytology alone or cytology with HPV triage annually or biennially.For both vaccinated and unvaccinated women, age-based screening by use of HPV DNA testing as a triage test for equivocal results in younger women and as a primary screening test in older women is expected to be more cost-effective than current screening recommendations.
Nurse led care: Nurses are autonomous professionals delivering expert care
Authors: Jonathan R Benger, Rebecca Hoskins
Journal: BMJ (2005)

This week in the BMJ for the paper by Walsh et al are offered the conclusion that investment in intermediate care in community hospitals may be more cost effective than financing nurse led care for post-acute patients in acute hospitals. 1 2But the study itself, which confirms existing evidence on the costs of nurse led intermediate care in acute settings, 3 4 tackles neither the effect nor the cost of intermediate care in community hospitals.How then can such a conclusion be drawn?Walsh et al do not make this assertion.The author of the comment offers no support.Our own review of the evidence on nurse led intermediate care found no quality evidence for either the effect or cost of intermediate care in community settings. 5 The BMJ has been at the forefront of setting standards for the reporting of primary research.However, the editors must be aware that many readers simply pick up a take home message from comment, like this, 1 in the journal.
(NZW x BXSB)F1 hybrid. A model of acute lupus and coronary vascular disease with myocardial infarction.
Authors: L M Hang, S Izui, F J Dixon
Journal: The Journal of Experimental Medicine (1981)

Both sexes of the (NZW x BXSB)F1 mice developed an early systemic lupus erythematosus-like disease. In males, the disease resembled that in the BXSB male parent and was not affected by sex hormonal manipulation. In females, the disease duplicated that of (NZB x NZW)F1 females by virtue of a delayed onset and estrogen dependence. Autoantibody production, circulating Ig-bound gp 70 immune complexes, and deposition of Ig and gp 70 in the affected glomeruli were demonstrated in both males and females. The abnormally high incidence of degenerative coronary vascular disease with myocardial infarction, particularly in these F1 males, provides a useful model for the investigation of a possible immunologic component in coronary vascular disease.
Intravascular and extravascular pulmonary fluid volumes. III Response to sustained left atrial hypertension
Authors: R. A SLUTSKY, C. B HIGGINS
Journal: Cardiovascular Research (1983)

The response of intravascular (PBV) and extravascular (EVLW) pulmonary fluid volumes was examined using double indicator techniques (thermal-green dye) in five open-chest anaesthetised dogs during the production of sustained left atrial (LA) hypertension by LA balloon. Left atrial pressure was abruptly increased from 0.16±0.15 to 3.96±0.51 kPa (1.2±1.1 to 29.8±3.8 mmHg) (P<.001) and maintained at that level for 120 min. Data were obtained prior to pressure elevation, immediately upon pressure elevation, and then every 30 min for a total of 2 h. PBV increased initially (209.7±78.2 to 377.5±92.1 cm3. P<0.01 but subsequently slowly declined (294.6±103.5 at 120 min P<0.05 vs peak value). Alternatively, EVLW increased slowly at first (260.6±77.9 to 291.3 ± 71.5 cm3), but more rapidly as time progressed (714.6±68.5 cm3 at 120 min P<.001 vs control or initial level). As EVLW rose and time passed after elevation of left atrial pressure, pulmonary vascular resistance (PVR) increased. In each animal, the relationship between the EVLW and PVR was linear (excluding the control point) with r values ≥0.91. With the initial increase in left atrial pressure, cardiac output (CO) declined (2.09±0.51 to 1.67±0.60 litre·min−1). As time passed, CO continued to decline in association with increases in EVLW and PVR. Thus, we conclude that with sustained LA hypertension there ensues an early rise in PA followed by increases in EVLW. The rise in EVLW has a direct linear relationship with the subsequent elevation of PVR suggesting that accumulation of EVLW is at least in part responsible for the change in PVR occuring in response to pulmonary venous hypertension.
Normal B Cell Homeostasis Requires B Cell Activation Factor Production by Radiation-resistant Cells
Authors: Leonid Gorelik, Kevin Gilbride, Max Dobles, Susan L. Kalled, Daniel Zandman, Martin L. Scott
Journal: The Journal of Experimental Medicine (2003)

The cellular source of B cell activation factor (BAFF) required for peripheral B cell survival/maturation is unknown. To determine the nature of BAFF-producing cells we established and analyzed reciprocal bone marrow (BM) chimeras with wild-type (WT) and BAFF-deficient mice. The results revealed that BAFF production by radiation-resistant stromal cells is completely sufficient to provide a necessary signal for B cell survival/maturation, as BAFF-/- BM cells transferred into lethally irradiated WT mice gave rise to normal numbers of follicular (FO) and marginal zone (MZ) B cell subpopulations. On the other hand, transfer of WT BM into BAFF-/- lethally irradiated mice resulted only in minimal reconstitution of mature FO B cells and no restoration of MZ B cells. Thus, in the absence of BAFF+/+ stromal cells, BAFF production by BM-derived cells, presumably by macrophages, dendritic cells, and/or neutrophils, was not at all sufficient to support normal B cell homeostasis. Interestingly, immunization of both types of chimeras stimulated high levels of antigen-specific antibody secretion, indicating that either stromal cell- or hematopoietic cell-derived BAFF is sufficient for B cell antibody responses.
Associations between Body Composition, Circulating Interleukin-1 Receptor Antagonist, Osteocalcin, and Insulin Metabolism in Active Acromegaly
Authors: Thor Ueland, Stine L. Fougner, Kristin Godang, Tove Lekva, Leon J. Schurgers, Hanne Scholz, Bente Halvorsen, Thomas Schreiner, Pål Aukrust, Jens Bollerslev
Journal: Endocrine Reviews (2009)

ObjectivePatients with active acromegaly display a range of abnormalities in glucose metabolism. To elucidate interactions between bone and energy homeostasis in relation to excess GH, we sought to determine whether these patients were characterized by alterations in circulating levels of adipokines and cytokines and potential interactions with osteocalcin (OCN) and insulin resistance.
Prevalence of silicosis among employees of a Silica factory in Sri-Lanka
Authors: Anoma Siribaddana, Kiruna Wickramasekara, Kapila Senevirathna, Asanga Upul, Manil Pieris
Journal: European Respiratory Journal (2013)

Introduction  Silicosis is a well-recognized, pneumoconiosis associated with exposure to silica dust. The silica industry is rapidly expanding in Sri Lanka, increasing the risk of occurrence of Silicosis.  The objective is to assess the prevalence of silicosis among workers exposed to silica dust.  Methods  A silica industry with 250 employees was screened using a questioner. All symptomatic with cough and shortness of breathing were investigated. Details of intensity, duration of silica exposure and usage of protective measures were recorded. Chest radiography and spirometry were performed in all symptomatic patients. International Labor Organization criteria for diagnosis of silicosis were used for diagnosis.  Results  Out of 250 employees 25(10%) had respiratory symptoms. Chest rays of 14 workers (5.6%) showed abnormalities suggestive of silicosis. One worker had X ray changes suggestive of progressive massive fibrosis. Out of 14 patients 6 (42.8%) had duration of exposure less than 5y and 8 (57.2%) had 5 to 10y of exposure. Only 7 out of 14 patients (50%) had force vital capacity less than 80% of the predicted value at spirometry.  Conclusions  Silica workers at the investigated industrial facility are at a significant risk of developing silicosis. Duration of exposure in all workers was less than ten years suggesting accelerated silicosis. Education of employers and employees of silica industry, improvement of protective measures and regular monitoring of the factory environment as well as employees health should be undertaken to avert this deadly disease.
Persistent unconjugated hyperbilirubinemia after liver transplantation due to an abnormal bilirubin UDP-glucuronosyltransferase gene promotor sequence in the donor
Authors: Peter L.M. Jansen, Piter J. Bosma, Conny Bakker, Simon P.M. Lems, Maarten J.H. Slooff, Elizabeth B. Haagsma
Journal: Journal of Hepatology (1997)
Hepatic aldehyde dehydrogenase activity in liver diseases, with particular emphasis on alcoholic liver disease
Authors: Shujiro Takase, Akira Takada, Minoru Yasuhara, Mikihiro Tsutsumi
Journal: Hepatology (1989)

Hepatic aldehyde dehydrogenase isozyme activity was measured in 51 patients with various types of liver diseases, including 24 patients with alcoholic liver disease, to elucidate the relationship between hepatic aldehyde dehydrogenase activity and liver disease, especially alcoholic liver disease. The levels of low-K m and total aldehyde dehydrogenase activity in the liver decreased both in alcoholic and nonalcoholic liver disease patients, who showed an isoelectric focusing pattern of the usual type. There was no significant difference in the aldehyde dehydrogenase activity between alcoholic and nonalcoholic liver disease. In alcoholic liver disease, the decrease in the activity was significantly correlated with the progression of liver histology. The activity in liver cirrhosis was significantly lower than that in the other types of alcoholic liver disease. In nonalcoholic liver disease patients, the unusual type of hepatic aldehyde dehydrogenase activity observed was not different from the unusual type observed in nonhepatobiliary disease patients. These results indicate that the reduction of hepatic low-K m aldehyde dehydrogenase activity is a change that occurs subsequent to liver damage. Genetic abnormality in aldehyde dehydrogenase may not be important in the pathogenesis of alcoholic liver injury.
Acid sphingomyelinase modulates the autophagic process by controlling lysosomal biogenesis in Alzheimer’s disease
Authors: Jong Kil Lee, Hee Kyung Jin, Min Hee Park, Bo-ra Kim, Phil Hyu Lee, Hiromitsu Nakauchi, Janet E. Carter, Xingxuan He, Edward H. Schuchman, Jae-sung Bae
Journal: The Journal of Experimental Medicine (2014)

In Alzheimer’s disease (AD), abnormal sphingolipid metabolism has been reported, although the pathogenic consequences of these changes have not been fully characterized. We show that acid sphingomyelinase (ASM) is increased in fibroblasts, brain, and/or plasma from patients with AD and in AD mice, leading to defective autophagic degradation due to lysosomal depletion. Partial genetic inhibition of ASM (ASM+/−) in a mouse model of familial AD (FAD; amyloid precursor protein [APP]/presenilin 1 [PS1]) ameliorated the autophagocytic defect by restoring lysosomal biogenesis, resulting in improved AD clinical and pathological findings, including reduction of amyloid-β (Aβ) deposition and improvement of memory impairment. Similar effects were noted after pharmacologic restoration of ASM to the normal range in APP/PS1 mice. Autophagic dysfunction in neurons derived from FAD patient induced pluripotent stem cells (iPSCs) was restored by partial ASM inhibition. Overall, these results reveal a novel mechanism of ASM pathogenesis in AD that leads to defective autophagy due to impaired lysosomal biogenesis and suggests that partial ASM inhibition is a potential new therapeutic intervention for the disease.
The Changing “Weightscape” of Bulimia Nervosa
Authors: Cynthia M. Bulik, Marsha D. Marcus, Stephanie Zerwas, Michele D. Levine, Maria La Via
Journal: American Journal of Psychiatry (2012)

Standard treatments for bulimia nervosa are for patients with normal weight, but a growing proportion of patients are substantially overweight or obese. Weight-related medical problems require coordination with primary care and expanded treatment goals. Cognitive-behavioral therapy (CBT), the gold standard for bulimia nervosa, is fairly ineffective in reducing weight. Compatible strategies tested for binge-eating disorder include appetite awareness training, behavioral weight loss, and appetite-focused CBT. A combined approach may be essential to treatment adherence, as patients are seeking weight loss. Nonetheless, goals of therapy include setting realistic expectations and shifting the focus from weight to health. Therapy groups specifically for overweight bulimia nervosa patients help avoid negative body comparisons.
Rapid Disuse Atrophy of Diaphragm Fibers in Mechanically Ventilated Humans
Authors: Sanford Levine, Taitan Nguyen, Nyali Taylor, Michael E. Friscia, Murat T. Budak, Pamela Rothenberg, Jianliang Zhu, Rajeev Sachdeva, Seema Sonnad, Larry R. Kaiser, Neal A. Rubinstein, Scott K. Powers, Joseph B. Shrager
Journal: New England Journal of Medicine (2008)

The combination of complete diaphragm inactivity and mechanical ventilation (for more than 18 hours) elicits disuse atrophy of myofibers in animals. We hypothesized that the same may also occur in the human diaphragm.
Regulatory T Cells in AKI
Authors: Gilbert R. Kinsey, Rahul Sharma, Mark D. Okusa
Journal: Journal of the American Society of Nephrology (2013)

Human AKI is manifested by inflammation, and an early feature in the pathogenesis is the accumulation of immune cells in the kidney. To understand the pathophysiology of AKI, results from animal models have shown a causal relation between the leukocyte activation and infiltration to the kidney after kidney ischemia-reperfusion. Blocking the activation or trafficking of proinflammatory leukocytes into the kidney preserves renal function and histologic integrity. In contrast, the anti-inflammatory lymphocytes called regulatory T cells have an intrinsic renal-protective function and may represent a novel therapeutic approach and/or target for pharmacological manipulation to ameliorate AKI. This review will highlight the recent insight gained into the role and mechanisms of regulatory T cells in AKI.
Renal and intrarenal blood flow in non-cirrhotic portal hypertension
Authors: M. C. Kew, C. Limbrick, R. R. Varma, S. Sherlock
Journal: Gut (1972)

The effect of portal hypertension or the consequent portal circulatory changes on renal haemodynamics was studied using the (133)xenon washout technique. Renal blood flow was reduced in nine of 11 patients with non-cirrhotic portal hypertension and this was accompanied by a redistribution of intrarenal blood flow, the distribution to and flow rate through the outer cortex being reduced while juxtamedullary and medullary flow was maintained. With slight or moderate decreases in cortical flow glomerular filtration was normal but poor cortical perfusion was associated with low creatinine clearances. These findings raise the possibility that portal hypertension or portal circulatory changes may play a role in the pathogenesis of the renal haemodynamic changes and functional renal failure which frequently complicate advanced hepatic cirrhosis.
An unusual case of Hughes-Stovin syndrome
Authors: S Herb, M Hetzel, J Hetzel, J Friedrich, J Weber
Journal: European Respiratory Journal (1998)

In 1959 HUGHES and STOVIN described a syndrome consisting of multiple pulmonary aneurysms and peripheral venous thrombosis. Since that time several cases of the Hughes-Stovin syndrome have been published. We present the case of a 25 yr old man who, in addition to the classical symptoms, had multiple aneurysms of the bronchial arteries, which were the cause of severe haemoptysis. An aneurysm of the left hepatic artery was also detected. To our knowledge this is the first description of aneurysms of the bronchial arteries in Hughes-Stovin syndrome. Bleeding was successfully treated by double embolization of bronchial arteries via transfemoral catheter.
Fabrication, characterization, and biological assessment of multilayered DNA-coatings for biomaterial purposes
Authors: Jeroen J.J.P. van den Beucken, Matthijn R.J. Vos, Peter C. Thüne, Tohru Hayakawa, Tadao Fukushima, Yoshio Okahata, X. Frank Walboomers, Nico A.J.M. Sommerdijk, Roeland J.M. Nolte, John A. Jansen
Journal: Biomaterials (2005)
Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis.
Authors: T Wada, N Tomosugi, T Naito, H Yokoyama, K Kobayashi, A Harada, N Mukaida, K Matsushima
Journal: The Journal of Experimental Medicine (1994)

Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untreated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli by 40% and dramatically prevented the fusion of epithelial cell foot process. Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 +/- 0.15 and 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.