tbuckley/cabot-search huggingface dataset:
Close relationship between microalbuminuria and insulin resistance in essential hypertension and non-insulin dependent diabetes mellitus.
Authors: R Nosadini, M R Cipollina, A Solini, M Sambataro, A Morocutti, A Doria, P Fioretto, E Brocco, B Muollo, F Frigato
Journal: Journal of the American Society of Nephrology (1992)

The aim of this study was to investigate the relationships among insulin resistance and albumin excretion rate in 25 nondiabetic patients with essential hypertension and in 28 patients with non-insulin dependent diabetes mellitus (NIDDM). Two groups of healthy subjects matched for age, sex, and weight served as controls. Patients with essential hypertension were divided into two subgroups: without (H1) and with (H2) microalbuminuria. Diabetic patients were divided into four subgroups: those with normoalbuminuria without (NIDDM1) and with (NIDDM2) hypertension and those with microalbuminuria without (NIDDM3) and with (NIDDM4) hypertension. Whole-body glucose utilization during euglycemic hyperinsulinemic clamp (40 mU/m2/min insulin infusion) was calculated by tracer dilution techniques (6,6 2H2 glucose tracer continuous infusion) and was significantly lower in hypertensives with microalbuminuria than in those without (H2 versus H1 versus controls: 3.41 +/- 0.51 versus 6.52 +/- 0.62 versus 7.03 +/- 0.48 mg/kg/min; mean +/- SE). Whole-body glucose utilization in NIDDM patients--NIDDM4 versus NIDDM3 versus NIDDM2 versus NIDDM1 versus controls--was: 1.86 +/- 0.31 versus 2.21 +/- 0.39 versus 2.01 +/- 0.40 versus 5.98 +/- 0.77 versus 5.52 +/- 0.92 mg/kg/min (mean +/- SE). Whereas the first three subgroups did not differ among themselves, they had significantly lower glucose utilization than did the normotensive NIDDM1 patients without microalbuminuria and nondiabetic controls (P < 0.01). Hypertensives with microalbuminuria had higher Vmax of sodium-lithium countertransport (Na/Li CTT) in red blood cells than did both hypertensives without microalbuminuria and controls. It was also observed that NIDDM patients with microalbuminuria had higher Vmax of Na/Li CTT than did NIDDM patients without microalbuminuria and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
STUDIES ON THE ETIOLOGY OF SPONTANEOUS CONJUNCTIVAL FOLLICULOSIS OF MONKEYS
Authors: Peter K. Olitsky, Joseph R. Tyler
Journal: The Journal of Experimental Medicine (1933)

Spontaneous folliculosis of Macacus rhesus monkeys-a type of follicular conjunctivitis associated with marked, local, inflammatory reactions-is apparently a disease sui generis, due to a specific infectious agent. It can be transmitted from monkey to monkey by means of subconjunctival injection of suspensions, and by conjunctival swabbing of the secretions, of affected tissues, or by contact of normal animals with folliculosis monkeys. The agent causing folliculosis has failed in our hands to pass through Berkefeld and Seitz filters, even those of an unusual degree of permeability; and the lesions that it causes show no cellular inclusions suggestive of the action of a virus. The condition is due apparently to an organism of low grade pathogenicity. The essential histopathological structure corresponds to that of a folliculoma (16) which, while not identical with a granuloma, bears certain resemblances to the latter. The studies here reported concern only one species of monkey, Macacus rhesus. Further investigations will be carried out on different species of Anthropoidea and other animals.
Inhaled antibiotics: dry or wet?
Authors: Harm A.W.M. Tiddens, Aukje C. Bos, Johan W. Mouton, Sunalene Devadason, Hettie M. Janssens
Journal: European Respiratory Journal (2014)

Dry powder inhalers (DPIs) delivering antibiotics for the suppressive treatment of Pseudomonas aeruginosa in cystic fibrosis patients were developed recently and are now increasingly replacing time-consuming nebuliser therapy. Noninferiority studies have shown that the efficacy of inhaled tobramycin delivered by DPI was similar to that of wet nebulisation. However, there are many differences between inhaled antibiotic therapy delivered by DPI and by nebuliser. The question is whether and to what extent inhalation technique and other patient-related factors affect the efficacy of antibiotics delivered by DPI compared with nebulisers. Health professionals should be aware of the differences between dry and wet aerosols, and of patient-related factors that can influence efficacy, in order to personalise treatment, to give appropriate instructions to patients and to better understand the response to the treatment after switching. In this review, key issues of aerosol therapy are discussed in relation to inhaled antibiotic therapy with the aim of optimising the use of both nebulised and DPI antibiotics by patients. An example of these issues is the relationship between airway generation, structural lung changes and local concentrations of the inhaled antibiotics. The pros and cons of dry and wet modes of delivery for inhaled antibiotics are discussed.
Increased galectin-3 expression and intra-epithelial neutrophils in small airways in severe COPD
Authors: C. Pilette, B. Colinet, R. Kiss, S. Andre, H. Kaltner, H-J. Gabius, M. Delos, J-P. Vaerman, M. Decramer, Y. Sibille
Journal: European Respiratory Journal (2007)

Galectins-1 and -3 regulate epithelial proliferation/apoptosis and neutrophil activation, and are implicated in lung cancer and asthma. The role of galectins in chronic obstructive pulmonary disease (COPD), characterised by epithelial changes and neutrophil infiltration, remains unknown. In the present study, galectin-1 and -3 expression was assessed by immunohistology in the bronchial epithelium of lung specimens from eight severe COPD patients and compared with nine nonsmokers and six smokers without COPD. Findings were related to epithelial proliferation (Ki-67), tissue inflammation and lung function. Epithelial galectin-3 immunostaining was increased only in the small airways of COPD patients when compared with nonsmokers and smokers. In contrast, galectin-1 was only significantly increased in the small airways of the group of smokers. Ki-67+ epithelial cells and neutrophils were increased in the small airways of COPD patients when compared with smokers. Furthermore, intra-epithelial neutrophils correlated in the small airways with Ki-67+ epithelial cells and with the forced expiratory volume in one second/forced vital capacity ratio. However, no correlation was observed with galectin expression. The present study supports the hypothesis that distal airways represent an important site for detecting changes in chronic obstructive pulmonary disease. In patients with severe disease, an increased galectin-3 expression and neutrophil accumulation in the small airway epithelium was demonstrated, correlating with epithelial proliferation and airway obstruction.
Potential Pitfalls in the Use of Glucoscan and Glucoscan II Meters for Self-Monitoring of Blood Glucose
Authors: Victor G Laus, Mark A Dietz, Richard P Levy
Journal: Diabetes Care (1984)

We discovered that skilled nurses only casually trained in the use of a fingertip blood glucose reflectance meter (Glucoscan, Lifescan, Mountainview, California) had a 36% incidence of unacceptable results (&amp;gt; 15% from reference). A controlled study was undertaken and showed that with Glucoscan I (GI) 4 of 27 readings were unacceptable and with Glucoscan II (GII) 3 of 27 readings were unacceptable, a statistically nonsignificant difference. Minor deviations from the manufacturer's recommended technique had a significant effect on the results with GI. In contrast, GII was much less sensitive to variations in recommended technique. GI underestimated the reference glucose concentration by 11.7%, and GII overestimated by 6.5%, a statistically significant difference. We conclude that the health professional must be aware of interdevice and intradevice variability in self-monitoring of blood glucose (SMBG). Patients need careful training in the method of SMBG. The results of any single value should be interpreted with caution.
[530] ENVIRONMENT CONTAMINATION AND BREACHES IN THE UNIVERSAL PRECAUTIONS ARE THE CAUSES OF HCV TRANSMISSION IN HEMODIALYSIS UNITS
Authors: S. Chevaliez, E. Girou, D. Challine, M. Thiessart, Y. Morice, P. Lesprit, L. Tkoub-Scheirlinck, S. Soing-Altrach, F. Cizeau, C. Cavin, M. Andre, P. Lang, J.-M. Pawlotsky
Journal: Journal of Hepatology (2007)
Association study of PHOX2B as a candidate gene for Hirschsprung's disease
Authors: M Garcia-Barcelo
Journal: Gut (2003)

<b>Background:</b> Hirschsprung’s disease (HSCR) is a congenital disorder characterised by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. Manifestation of the disease has been linked to mutations in genes that encode the crucial signals for the development of the enteric nervous system—the RET and EDNRB signalling pathways. The <i>Phox2b</i> gene is involved in neurogenesis and regulates <i>Ret</i> expression in mice, in which disruption of the <i>Phox2b</i> results in a HSCR-like phenotype. <b>Aims:</b> To investigate the contribution of <i>PHOX2B</i> to the HSCR phenotype. <b>Methods:</b> Using polymerase chain reaction amplification and direct sequencing, we screened <i>PHOX2B</i> coding regions and intron/exon boundaries for mutations and polymorphisms in 91 patients with HSCR and 71 ethnically matched controls. Seventy five HSCR patients with no <i>RET</i> mutations were independently considered. Haplotype and genotype frequencies were compared using the standard case control statistic. <b>Results:</b> Sequence analysis revealed three new polymorphisms: two novel single nucleotide polymorphisms (A→G<sub>1364</sub>; A→C<sub>2607</sub>) and a 15 base pair deletion (DEL<sub>2609</sub>). Statistically significant differences were found for A→G<sub>1364</sub>. Genotypes comprising allele G were underrepresented in patients (19% <i>v</i> 36%; χ<sup>2</sup>=9.30; p<i>=</i>0.0095 and 22% <i>v</i> 36%; χ<sup>2</sup>=7.38; p<i>=</i>0.024 for patients with no <i>RET</i> mutations). Pairwise linkage disequilibrium (LD) analysis revealed no LD between physically close polymorphisms indicating a hot spot for recombination in exon 3. <b>Conclusion:</b> The <i>PHOX2B</i> A→G<sub>1364</sub> polymorphism is associated with HSCR. Whether it directly contributes to disease susceptibility or represents a marker for a locus in LD with <i>PHOX2B</i> needs further investigation. Our findings are in accordance with the involvement of <i>PHOX2B</i> in the signalling pathways governing the development of enteric neurones.
Incidence of Arrhythmias in the Dog Following Transthoracic Ventricular Defibrillation with Unidirectional Rectangular Stimuli
Authors: HARRY STOECKLE, STEPHEN H. NELLIS, JOHN C. SCHUDER
Journal: Circulation Research (1968)

The incidence of the various types of arrhythmia induced by defibrillation in anesthetized dogs that had had continous ventricular fibrillation for 30 seconds was studied as a function of the current strengh and the duration of the unidirectional rectangular pulse used to terminate the fibrillation. Shocks at 10, 20, 40, 80, and 100 amp with durations in the range of 80 µsec through 64 msec were used. At any given energy level the incidence of induced arrhythmias was much larger for the 40-, 80-, and 100-amp shocks than for the 10- and 20-amp shocks. At 10 and 20 amp, the incidence of induced arrhythmias increased with increasing energy content. Premature ventricular contractions were observed at nearly all levels of energy and current, in contrast to other types of arrhythmias that appear to be strongly related to energy content or current amplitude or both.
Endothelial Localization of Receptor Tyrosine Phosphatase, ECRTP/DEP-1, in Developing and Mature Renal Vasculature
Authors: TAKAMUNE TAKAHASHI, KEIKO TAKAHASHI, RAYMOND MERNAUGH, VLADIMIR DROZDOFF, CHRIS SIPE, HARALD SCHOECKLMANN, BARRY ROBERT, DALE R. ABRAHAMSON, THOMAS O. DANIEL
Journal: Journal of the American Society of Nephrology (1999)

Developmental assembly of the renal microvasculature requires spatially and temporally coordinated migration, assembly, differentiation, and maturation of endothelial cells in the context of adjacent epithelial and mesangial cells. In this study, endothelial expression and distribution of the receptor tyrosine phosphatase ECRTP/DEP-1 were evaluated during and after developmental assembly of the renal microvasculature. Monoclonal antibodies against ECRTP/DEP-1 ectodomain epitopes localize its expression to membrane surfaces of endothelial cells in glomerular, peritubular capillary, and arterial renal sites of mature human and murine kidney. During kidney development, ECRTP/DEP-1 immunostaining is evident on a subpopulation of metanephric mesenchymal cells and on putative progenitors of glomerular capillary endothelial cells early in their recruitment to developing glomeruli. ECRTP/DEP-1 is prominently displayed on luminal membrane surfaces with punctate accumulations at inter-endothelial contacts that overlap with vascular endothelial-cadherin staining. ECRTP/DEP-1 is recruited to inter-endothelial contacts in confluent cultured human renal and dermal microvascular endothelial cells, yet experimental dissociation of vascular endothelial-cadherin from endothelial junctional complexes fails to redistribute ECRTP/DEP-1. These findings indicate that ECRTP/DEP-1 is expressed in anticipation of glomerular capillary endothelial recruitment during development, and suggest that ECRTP/DEP-1 ectodomain interacts with endothelial surface ligands that are engaged by cell-cell contact.
Predicting Chemotherapy Toxicity in Older Adults and the Importance of Geriatric Assessment
Authors: Joep Lagro, Stephanie A. Studenski, Marcel G.M. Olde Rikkert
Journal: Journal of Clinical Oncology (2011)

The article by Hurria et al 1 provides invaluable evidence that geriatric assessment complements medical factors in predicting chemotherapy treatment tolerance in older adults.This is an important step forward in care planning for older adults, not only in oncology but also in the management of other common health problems of aging.We note how many of the geriatric assessment variables detected in the univariate and multivariate analyses were related to mobility status.Although Hurria et al 2 previously explained that the screening tool used in this study 1 was designed to be self-administered and therefore limited to a questionnaire, we are struck that several key geriatric factors found in this study (ability to walk one block, decreased social activities because of physical or emotional problems, falls in the last 6 months) might also be detectable by a simple performance test of mobility.In the field of geriatrics, there is substantial evidence that simple performance tests like gait speed are themselves powerful predictors of multiple outcomes. 3Performance tests can be feasible in busy clinical practice; they can be brief, be completed by staff in minutes, and provide objective results.At minimum, they can complement self-report, but they can also detect impairments that are not acknowledged by the individual.Walking speed has been shown to be a powerful complement to medical factors in predicting treatment tolerance and adverse outcomes in other important interventions for older adults, such as cardiac surgery. 4e note that although only the self-reported geriatric assessment items were included in the predictive models, the study 1 did have a provider section that included not only Karnofsky performance status but also a test of walking speed (Timed Up and Go).Although the results were assessed against the Karnofsky scale, Timed Up and Go was not evaluated in the multivariable models; however, it was a significant univariate predictor.We wonder if the model receiver operating characteristic curves would be equivalent or even better if walking speed had been assessed instead of or in addition to the self-reported items.We also recommend that cutoff points other than 10 seconds be assessed, because the range and potential cutoff points for walking speed are broad. 3his study 1 has immediate clinical implications for older patients with cancer in that the results can help inform patients who have been referred to oncologists about the risks of chemotherapy.As a component of shared decision making, we suspect that some patients may use this information to select less aggressive care.Prior studies have suggested that some older patients, informed with a decision aid, prefer treatment options of lower intensity than physicians would expect.For example, 71% of 150 older patients with prostate cancer preferred lower-dose radiation, whereas physicians' own preference favored the lower dose in only 20% of the patients. 5
Intracellular calcium storage and release in the human platelet. Chlorotetracycline as a continuous monitor.
Authors: W Jy, D H Haynes
Journal: Circulation Research (1984)

The calcium-sensitive fluorescent probe chlorotetracycline was used to monitor calcium movement in human platelets. The chlorotetracycline fluorescence signal is a linear measure of the level of free calcium in the dense tubules and in the mitochondria, with probe sensitivity in the millimolar range. Experiments perturbing the system with the calcium ionophore A23187 shows that the level of free internal calcium in the organelle depends upon the cytoplasmic level, which, in turn, depends upon the passive permeability of the plasma membrane. Chlorotetracycline in the cytoplasmic compartment does not respond to changes in the cytoplasmic calcium concentration, which is held in the micromolar to submicromolar range by an extrusion system. The calcium concentration in the cytoplasmic compartment can be directly manipulated by the calcium ionophore A23187 and is measured in parallel experiments with Quin 2, a high-affinity indicator. The calcium transport systems of the organelles are shown to be less susceptible to short circuit by A23187. Analysis shows that mitochondrial uptake is slow (t 1/2 = 20 minutes), produces a large increase in chlorotetracycline fluorescence, and is inhibited by sodium azide plus oligomycin. Uptake by the dense tubules is more rapid (t 1/2 = 2 minutes), produces a smaller increase in chlorotetracycline fluorescence, is inhibited by trifluoperazine, and is less sensitive to A23187. The Km is estimated as 1 microM or lower. Studies show that the chlorotetracycline technique is useful for the monitoring of calcium uptake and release by the platelet organelles, and suggests that the Quin 2/chlorotetracycline technique will be useful as a diagnostic of both physiological and pathological activation mechanisms.
Hyaluroman syntehase-2 over expression has impact in the evolution and on the prognosis of idiopathic pulmonary fibrosis patients
Authors: Edwin Roger Parra, Vera Capelozzi
Journal: European Respiratory Journal (2012)

Background: The idiopathic pulmonary fibrosis (IPF) is a terminal illness characterized by unremitting extracellular matrix (ECM) deposition. In this regard, the myofibroblasts and the ECM components such as hyaluronan (HA) have an important role in the fibrosis. We analyzed the expression of HAS1 (HA synthase 1), HAS2, HAS3 and hyaluronic acid receptor (CD44) by epithelial and myofibroblasts cells in patients with IPF and we correlated with a survival.

Methods: HAS-1, HAS2, HAS3 and CD44 epithelial and myofibroblast expression were evaluated in 27 surgical lung biopsies from patients with IPF in minimal and severe fibrosis by the point-counting technique. Impact of these markers was tested on pulmonary functional tests and follow-up until death from IPF.

Results: HAS2 and CD44 expression were significantly increased and directly associated with severe fibrosis. Myofibroblast HAS2 activity was indirectly associated to DLO/VA (r=-0.584; p=0.05). Kaplan Maier curves determined a higher risk of death for patient with high HA2 (>6.83%) expression than in low expression (Log Rank p=0.05).

![Figure][1] 



Conclusion: The increased HAS-2 activity in epithelial and myofibroblast cells have impact in the remodeling process and the survival evolution, suggesting that strategies aimed at preventing the effect of this ECM component may have a greater impact in patient's outcome.

Financial Support: FAPESP.

 [1]: pending:yes
Selective inhibition of T cell proliferation but not expression of effector function by human alveolar macrophages
Authors: J. W. Upham, D. H. Strickland, B. W. Robinson, P. G. Holt
Journal: Thorax (1997)

BACKGROUND: Alveolar macrophages are thought to play an important part in regulating lung immune responses. While it is clear that human alveolar macrophages suppress T cell proliferation in vitro, the mechanisms by which this is achieved are not clear, nor is it known whether alveolar macrophages also inhibit other aspects of T cell function. METHODS: Peripheral blood mononuclear cells were stimulated with phytohaemagglutinin or house dust mite allergen, and cultured with variable numbers of autologous alveolar macrophages obtained by bronchoalveolar lavage from 20 normal subjects. RESULTS: Alveolar macrophages induced a reversible inhibition of T cell proliferation in response to both mitogen and allergen stimulation, with the latter being considerably more susceptible to inhibition. This was achieved via heterogenous mechanisms, involving both soluble factors derived from alveolar macrophages and cell-cell contact. Despite inhibiting proliferation, alveolar macrophages had little or no effect on T cell calcium flux, the characteristic changes in CD3, CD2, CD28 and interleukin-2 (IL-2) receptor expression which accompany normal T cell activation, and IL-2 and interferon gamma secretion. In contrast, alveolar macrophages inhibited the tyrosine phosphorylation of proteins which may be involved in IL-2 receptor-associated signal transduction. CONCLUSIONS: The immunoregulatory properties of alveolar macrophages are relatively selective, allowing T cell activation and cytokine secretion while inhibiting T cell proliferation within the lung.
Visualizing multidimensional cancer genomics data
Authors: Michael P Schroeder, Abel Gonzalez-Perez, Nuria Lopez-Bigas
Journal: Genome Medicine (2013)

Cancer genomics projects employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Examples include projects carried out by the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). A crucial step in the extraction of knowledge from the data is the exploration by experts of the different alterations, as well as the multiple relationships between them. To that end, the use of intuitive visualization tools that can integrate different types of alterations with clinical data is essential to the field of cancer genomics. Here, we review effective and common visualization techniques for exploring oncogenomics data and discuss a selection of tools that allow researchers to effectively visualize multidimensional oncogenomics datasets. The review covers visualization methods employed by tools such as Circos, Gitools, the Integrative Genomics Viewer, Cytoscape, Savant Genome Browser, StratomeX and platforms such as cBio Cancer Genomics Portal, IntOGen, the UCSC Cancer Genomics Browser, the Regulome Explorer and the Cancer Genome Workbench.