tbuckley/cabot-search huggingface dataset:
The renin-aldosterone axis in two models of reduced renal mass in the rat.
Authors: H N Ibrahim, T H Hostetter
Journal: Journal of the American Society of Nephrology (1998)

The renin-angiotensin-aldosterone system participates in chronic progressive renal disease. The studies presented here assessed the importance of aldosterone in two different methods of reduced kidney mass in the rat, i.e., the infarction model (INF; uninephrectomy plus infarction of approximately two-thirds of the other kidney) and surgical excision or polectomy (POL; uninephrectomy plus surgical excision of both poles of the other kidney). Equivalent degrees of reduction in renal mass were confirmed by the similarity of serum creatinines 3 d after the ablative procedure. Measurements were made thereafter at 2 and 4 wk postablation. Systolic arterial pressure was greater with INF at both 2 and 4 wk. Proteinuria was also greater in the INF group at both time periods. The percentage of glomeruli with sclerosis measured at 4 wk tended to be greater in the INF group; however, this difference was not of statistical significance. At 2 wk, plasma renin activity and plasma aldosterone levels were lower in the POL group. The renin concentration in the scar region of the kidneys in the INF group was higher than in the kidney of the POL group. In conjunction with the lower plasma aldosterone, rats in the POL group had higher plasma potassium concentrations at 2 wk. In summary, higher aldosterone and plasma renin levels distinguish the INF model from the POL and likely contribute to the greater proteinuria and hypertension in the INF model.
Human renal cortical interstitial cells with some features of smooth muscle cells participate in tubulointerstitial and crescentic glomerular injury.
Authors: C E Alpers, K L Hudkins, J Floege, R J Johnson
Journal: Journal of the American Society of Nephrology (1994)

In most forms of renal injury, even those due to a primary glomerular process, the extent of tubulointerstitial scarring is a critical determinant of renal functional reserve and prognosis. Yet, little is known about the functional characteristics of the interstitial cells that mediate the processes of chronic tubulointerstitial injury. In this study, tissues from normal kidney (N = 7), from nephrectomies removed for allograft rejection (N = 14) and chronic pyelonephritis (N = 2), and from a cohort of 128 biopsies exhibiting a range of glomerulopathies and tubulointerstitial injury were characterized with antibodies to mesenchymal cells (alpha-smooth muscle actin, desmin) by immunohistology. Selected normal kidneys were also studied by immunoelectron microscopy. Normal adult kidneys contain a widespread population of cortical interstitial cells that constitutively express alpha-smooth muscle actin but not desmin. Immunoelectron microscopy shows that these cells are fibroblasts and not capillary endothelial cells or leukocytes. It has previously been shown that these cells constitutively express platelet-derived growth factor receptor beta and the p75 nerve growth factor receptor. Accumulations of cells expressing smooth muscle actin were identified at sites of chronic tubulointerstitial injury in allograft and pyelonephritic kidneys. The cohort of 128 renal biopsies also revealed accumulations of muscle actin-expressing cells at sites of interstitial injury. These findings demonstrate that a population of interstitial cells with some muscle-like features can be identified in normal kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
Rituximab-induced lung disease: a systematic literature review
Authors: H Lioté, F Lioté, B Séroussi, C Mayaud, J Cadranel
Journal: European Respiratory Journal (2009)

The anti-CD20 antibody rituximab has been reported to induce a heterogeneous spectrum of lung disorders. The aim of the present study was to critically review data on the clinical presentations, causality assessments and management strategies of lung diseases possibly related to rituximab. A systematic literature review was performed on English-language reports in PubMed until September 2008. Cases of lung diseases ascribed to rituximab (n = 45) were identified, with three time-to-onset patterns. The most common presentation was acute/subacute hypoxaemic organising pneumonia (n = 37), starting 2 weeks after the last infusion (often around the fourth cycle) and resolving, in most cases, provided glucocorticoid therapy was given early. Acute respiratory distress syndrome occurred in five patients, within a few hours and usually after the first infusion. In the remaining three patients, macronodular organising pneumonia developed insidiously long after rituximab therapy and responded to steroids. Eight patients died. Based on time to onset, symptoms, and responses to discontinuation and rechallenge with rituximab and other drugs, 13 cases were highly compatible and 32 compatible with rituximab-induced lung disease. Knowledge of these presentations of rituximab-induced lung disease should prove helpful for diagnosis and causality assessment purposes. Time-to-onset data, suggesting different pathogenic mechanisms, support closer clinical and perhaps radiological monitoring between infusions, particularly in patients with a history of reversible respiratory symptoms.
A CONTRIBUTION TO THE PATHOLOGY OF EPIDEMIC POLIOMYELITIS
Authors: Simon Flexner, Paul F. Clark, Harold L. Amoss
Journal: The Journal of Experimental Medicine (1914)

The virus of poliomyelitis is neurotropic, and localizes, and probably is capable of multiplying in the extramedullary parenchymatous nervous organs. It has been demonstrated by inoculation tests in the intervertebral, Gasserian, and abdominal sympathetic ganglia. All the ganglia show histological lesions, more or less severe, similar to those of the spinal cord and brain. The severest occur in the intervertebral ganglia, those next in severity in the Gasserian, while the mildest appear in the abdominal sympathetic ganglia. The interstitial lesions predominate over the parenchymatous, and in preparalytic stages the intervertebral ganglia show interstitial lesions, especially pronounced at the pial covering. Epidemic poliomyelitis is a general disease of the nervous system, although the most prominent and important symptoms are those following injury to the motor neurones of the spinal cord and brain. The virus of poliomyelitis is highly resistant to glycerin, in which it survives for more than two years; to 0.5 per cent. phenol, in which it survives for more than one year; while it succumbs after having been kept frozen constantly for several months. It is unsafe to employ phenol to modify the virus of poliomyelitis for the purpose of active immunization. The cerebrospinal fluid of convalescents tends to be devoid of the neutralizing immunity principles for the virus of poliomyelitis, although they may exceptionally be present within this fluid. Doubtless the immunity principles are not produced locally in the nervous tissues, but elsewhere in the body, and are carried to the nervous organs by the blood.
The role of transthoracic ultrasound (TTS) in the diagnosis and management of post transbronchial lung biopsy (TBLB) pnemothorax (PTX)
Authors: Sachin Kumar, Dheeraj Gupta, Ritesh Agarwal, Ashutosh Aggarwal, Surinder Kumar Jindal
Journal: European Respiratory Journal (2012)

BACKGROUND  TTS increasingly being used to detect PTX, however its utility in diagnosis and management of post TBLB PTX largely unknown.  OBJECTIVE  To evaluate the accuracy of TTS in detection of post TBLB PTX.  SUBJECTS AND METHODS  TTS performed on 379 consecutive patients undergoing flexible bronchoscopy and TBLB (n=113). Disappearance of sliding lung and comettail artifacts considered evidence of PTX. Upright chest radiography (CXR) was performed after 2 hours of TBLB. CT chest performed in case of discrepancy between TTS and CXR. PTX was sonographically monitored by noting position of the lung point 2 hrly.  RESULTS  PTX occurred in eight (7.1%) of TBLB patients. TTS depicted all cases of PTX while CXR did not depict one PTX, which was confirmed on CT. All PTX diagnosed immediately post procedure by TTS in the bronchoscopy suite itself. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were all 100% for TTS and 87.5%, 100%, 100%, 99.6%, and 99.6%, respectively, for CXR. The 95% confidence intervals (CI) for the sensitivity, negative predictive value, and overall accuracy were 46.7% to 99.3%, 95.6% to 100%, and 56.1% to 100% for CXR. Any shift of the lung point towards the base of lungs(below Mid thoracic line) favored single time aspiration (done in 2 cases) or ICTD insertion(1 case),while conservative management done in cases where lung point shifted towards apex(Above Mid thoracic line).  CONCLUSION These preliminary results suggest that TTS is as effective as CXR in the detection of PTX after TBLB and may become the method of choice for excluding, diagnosing, and monitoring PTX after TBLB.
Multispecies communities: interspecies interactions influence growth on saliva as sole nutritional source
Authors: Paul E Kolenbrander
Journal: International Journal of Oral Science (2011)

Human oral bacteria live in multispecies communities in the biofilm called dental plaque. This review focuses on the interactions of seven species and the ability of each species individually and together with other species to grow on saliva as the sole source of nutrient. Community formation in biofilms in flow cells is monitored using species‐specific fluorophore‐conjugated immunoglobulin G, and images are captured by confocal microscopy. Early colonizing veillonellae emerge from this review of interspecies interactions in saliva as a critical genus that guides the development of multispecies communities. Highly selective interspecies recognition is evident as initial colonizers pair with early and middle colonizers to form multispecies communities that grow on saliva.
Rapid Induction of Lung Adenocarcinoma by Fibroblast Growth Factor 9 Signaling through FGF Receptor 3
Authors: Yongjun Yin, Tomoko Betsuyaku, Joel R. Garbow, Jinbai Miao, Ramaswamy Govindan, David M. Ornitz
Journal: Cancer Research (2013)

Fibroblast growth factors (FGF) are expressed in many non-small cell lung carcinoma (NSCLC) primary tumors and derived cell lines, and mutations in FGF receptor 3 (FGFR3) have been identified in human lung adenocarcinoma. FGF9 has been implicated in the pathogenesis of NSCLC by synergizing with EGFR pathways or by providing an escape pathway mediating resistance to EGFR inhibition. To model pathogenic mechanisms mediated by FGF signals, we have established a mouse model in which FGF9 expression can be induced in adult lung epithelium. Here, we show that induced expression of FGF9 in adult lung leads to the rapid proliferation of distal airway epithelial cells that express the stem cell marker, Sca-1, and the proximal and distal epithelial markers, Sftpc and CC10, the rapid formation of Sftpc-positive adenocarcinomas, and eventual metastasis in some mice. Furthermore, we have identified FGFR3 as the obligate receptor mediating the FGF9 oncogenic signal. These results identify an FGF9-FGFR3 signal as a primary oncogenic pathway for lung adenocarcinoma and suggest that this pathway could be exploited for customized therapeutic applications for both primary tumors and those that have acquired resistance to inhibition of other signaling pathways.
Evolution of Gene Expression in Fire Ants: The Effects of Developmental Stage, Caste, and Species
Authors: L. Ometto, D. Shoemaker, K. G. Ross, L. Keller
Journal: Molecular Biology and Evolution (2010)

Ants provide remarkable examples of equivalent genotypes developing into divergent and discrete phenotypes.Diploid eggs can develop either into queens, which specialize in reproduction, or workers, which participate in cooperative tasks such as building the nest, collecting food, and rearing the young.In contrast, the differentiation between males and females generally depends upon whether eggs are fertilized, with fertilized (diploid) eggs giving rise to females and unfertilized (haploid) eggs giving rise to males.To obtain a comprehensive picture of the relative contributions of gender (sex), caste, developmental stage, and species divergence to gene expression evolution, we investigated gene expression patterns in pupal and adult queens, workers, and males of two species of fire ants, Solenopsis invicta and S. richteri.Microarray hybridizations revealed that variation in gene expression profiles is influenced more by developmental stage than by caste membership, sex, or species identity.The second major contributor to variation in gene expression was the combination of sex and caste.Although workers and queens share equivalent diploid nuclear genomes, they have highly distinctive patterns of gene expression in both the pupal and the adult stages, as might be expected given their extraordinary level of phenotypic differentiation.Overall, the difference in the proportion of differentially expressed genes was greater between workers and males than between workers and queens or queens and males, consistent with the fact that workers and males share neither gender nor reproductive capability.Moreover, between-species comparisons revealed that the greatest difference in gene expression patterns occurred in adult workers, a finding consistent with the fact that adult workers most directly experience the distinct external environments characterizing the different habitats occupied by the two species.Thus, much of the evolution of gene expression in ants may occur in the worker caste, despite the fact that these individuals are largely or completely sterile.Analyses of gene expression evolution revealed a combination of positive selection and relaxation of stabilizing selection as important factors driving the evolution of such genes.
Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy
Authors: Vishal Kothari, Iris Wei, Sunita Shankar, Shanker Kalyana-Sundaram, Lidong Wang, Linda W. Ma, Pankaj Vats, Catherine S. Grasso, Dan R. Robinson, Yi-Mi Wu, Xuhong Cao, Diane M. Simeone, Arul M. Chinnaiyan, Chandan Kumar-Sinha
Journal: Cancer Discovery (2013)

Protein kinases represent the most effective class of therapeutic targets in cancer; therefore, determination of kinase aberrations is a major focus of cancer genomic studies. Here, we analyzed transcriptome sequencing data from a compendium of 482 cancer and benign samples from 25 different tissue types, and defined distinct "outlier kinases" in individual breast and pancreatic cancer samples, based on highest levels of absolute and differential expression. Frequent outlier kinases in breast cancer included therapeutic targets like ERBB2 and FGFR4, distinct from MET, AKT2, and PLK2 in pancreatic cancer. Outlier kinases imparted sample-specific dependencies in various cell lines, as tested by siRNA knockdown and/or pharmacologic inhibition. Outlier expression of polo-like kinases was observed in a subset of KRAS-dependent pancreatic cancer cell lines, and conferred increased sensitivity to the pan-PLK inhibitor BI-6727. Our results suggest that outlier kinases represent effective precision therapeutic targets that are readily identifiable through RNA sequencing of tumors.
Time course of regression of left ventricular hypertrophy in hypertensive patients treated with atenolol.
Authors: F G Dunn, H O Ventura, F H Messerli, I Kobrin, E D Frohlich
Journal: Circulation (1987)

Regression of left ventricular hypertrophy occurs with a number of antihypertensive drugs, but the time course of this regression has not been defined clearly. We obtained echocardiograms at baseline and serially (on seven occasions) during a 1 year treatment period with the beta-adrenergic receptor inhibitor atenolol in 12 patients with previously untreated essential hypertension. To ensure control of blood pressure in all patients throughout the study, it was necessary to add a thiazide diuretic to the therapy of five patients. Baseline blood pressure was 155/100 mm Hg and fell to 136/84 mm Hg; there was a 20% reduction in heart rate. Posterior and septal wall thicknesses were reduced from 1.16 +/- 0.03 to 1.06 +/- 0.02 cm (p less than .05) and from 1.28 +/- 0.07 to 1.18 +/- 0.06 cm (p less than .05), respectively; this reduction became significant initially at 4 weeks. Left ventricular mass decreased from 144 +/- 9 to 127 +/- 7 g/m2 (p less than .05) and this fall first became statistically significant at 6 months. Significant reduction in electrocardiographic voltages was also seen at 6 months. Therefore, regression of left ventricular hypertrophy with atenolol-induced blood pressure control occurred as early as 4 weeks after starting therapy and was maintained thereafter without apparent compromise of left ventricular systolic function.
'Light Up and Make My Day'
Authors: J. Paul Leigh
Journal: JAMA (1987)

To the Editor.—  Dr Cady 1 recently argued that nonsmokers subsidize smokers when the two groups are covered by the same group health plan because, although smokers and nonsmokers pay the same amount for the insurance, smokers require more medical care than the nonsmokers during any given year. Dr Cady's argument is undoubtedly correct for group health insurance for any given year , but it may not be correct over the life spans of smokers and nonsmokers.  The life-span argument can be most easily explained by considering who is subsidizing whom under the Social Security system. Employed smokers and nonsmokers pay the same Social Security payroll taxes. The great majority of Social Security beneficiaries are retirees, aged 62 years and over. It is likely that a disproportionate number of retirees never smoked or, if they did, quit before retirement. Smokers die earlier than nonsmokers. Some researchers believe that most of the
Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice
Authors: Mary K. Collins, Chin-Siean Tay, Adrian Erlebacher
Journal: Journal of Clinical Investigation (2009)

Embryo implantation induces formation of the decidua, a stromal cell–derived structure that encases the fetus and placenta. Using the mouse as a model organism, we have found that this tissue reaction prevents DCs stationed at the maternal/fetal interface from migrating to the lymphatic vessels of the uterus and thus reaching the draining lymph nodes. Strikingly, decidual DCs remained immobile even after being stimulated with LPS and exhibiting responsiveness to CCL21, the chemokine that drives DC entry into lymphatic vessels. An analysis of maternal T cell reactivity toward a surrogate fetal/placental antigen furthermore revealed that regional T cell responses toward the fetus and placenta were driven by passive antigen transport and thus the tolerogenic mode of antigen presentation that predominates when there is negligible input from tissue-resident DCs. Indeed, the lack of involvement of tissue-resident DCs in the T cell response to the fetal allograft starkly contrasts with their prominent role in organ transplant rejection. Our results suggest that DC entrapment within the decidua minimizes immunogenic T cell exposure to fetal/placental antigens and raise the possibility that impaired development or function of the human decidua, which unlike that of the mouse contains lymphatic vessels, might lead to pathological T cell activation during pregnancy.
Participation of mercuric conjugates of cysteine, homocysteine, and N-acetylcysteine in mechanisms involved in the renal tubular uptake of inorganic mercury.
Authors: R K Zalups, D W Barfuss
Journal: Journal of the American Society of Nephrology (1998)

Mechanisms involved in the renal uptake of inorganic mercury were studied in rats administered a nontoxic 0.5 mumol/kg intravenous dose of inorganic mercury with or without 2.0 mumol/kg cysteine, homocysteine, or N-acetylcysteine. The renal disposition of mercury was studied 1 h after treatment in normal rats and rats that had undergone bilateral ureteral ligation. In addition, the disposition of mercury (including the urinary and fecal excretion of mercury) was evaluated 24 h after treatment. In normal rats, coadministering inorganic mercury plus cysteine or homocysteine caused a significant increase in the renal uptake of mercury 1 h after treatment. The enhanced renal uptake of mercury was due to increased uptake of mercury in the renal outer stripe of the outer medulla and/or renal cortex. Ureteral ligation caused reductions in the renal uptake of mercury in all groups except for the one treated with inorganic mercury plus N-acetylcysteine. Thus, it appears that virtually all of the mercury taken up by the kidneys of the normal rats treated with inorganic mercury plus N-acetylcysteine occurred at the basolateral membrane. Urinary excretory data also support this notion, in that the rate of excretion of inorganic mercury was greatest in the rats treated with inorganic mercury plus N-acetylcysteine. Our data also indicate that uptake of inorganic mercury in the kidneys of rats treated with inorganic mercury plus cysteine occurred equally at both luminal and basolateral membranes. In addition, the renal uptake of mercury in rats treated with inorganic mercury plus homocysteine occurred predominantly at the basolateral membrane with some component of luminal uptake. The findings of the present study confirm that there are at least two distinct mechanisms involved in the renal uptake of inorganic mercury, with one mechanism located on the luminal membrane and the other located on the basolateral membrane. Our findings also show that cysteine and homologs of cysteine, when coadministered with inorganic mercury, greatly influence the magnitude and/or site of uptake of mercuric ions in the kidney.
BMP-7 Is an Efficacious Treatment of Vascular Calcification in a Murine Model of Atherosclerosis and Chronic Renal Failure
Authors: Matthew R. Davies, Richard J. Lund, Keith A. Hruska
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Chronic renal failure is complicated by high cardiovascular mortality. One key contributor to this mortality is vascular calcification, for which no therapy currently exists. Bone morphogenetic protein 7 is an essential renal morphogen that maintains renal tubular differentiation in the adult and is downregulated in renal failure. Several studies have demonstrated its efficacy in treating various renal diseases in rodents, and it was hypothesized that it would also be an effective treatment of vascular calcification in this setting. Uremia was imposed on LDL receptor null mice (a model of atherosclerosis), which were then treated with bone morphogenetic protein 7 for 15 wk. Uremic animals had increased vascular calcification by histology and chemical analysis. Calcification in treated animals was similar to or less than non-uremic control animals. Cells exhibiting an osteoblast-like phenotype in the vessel wall may be important in the etiology of vascular calcification. Expression of osteocalcin was assessed as a marker of osteoblastic function, and it is shown that it is increased in untreated uremic animals but downregulated to levels similar to non-uremic control animals with treatment. The data are compatible with bone morphogenetic protein 7 deficiency as a pathophysiologic factor in chronic renal failure, and they demonstrate its efficacy as a potential treatment of vascular calcification. E-mail: [email protected]