tbuckley/cabot-search huggingface dataset:
Renal Apolipoprotein A-I Amyloidosis
Authors: Gina Gregorini, Claudia Izzi, Laura Obici, Regina Tardanico, Christoph Ro[Combining Diaeresis]cken, Battista Fabio Viola, Mariano Capistrano, Simona Donadei, Luciano Biasi, Tiziano Scalvini, Giampaolo Merlini, Francesco Scolari
Journal: Journal of the American Society of Nephrology (2005)

Apolipoprotein A-I amyloidosis is a rare, late-onset, autosomal dominant condition characterized by systemic deposition of amyloid in tissues, the major clinical problems being related to renal, hepatic, and cardiac involvement. Described is the clinical and histologic picture of renal involvement as a result of apolipoprotein A-I amyloidosis in five families of Italian ancestry. In all of the affected family members, the disease was caused by the Leu75Pro heterozygous mutation in exon 4 of apolipoprotein A-I gene, as demonstrated by direct sequencing and RFLP analysis. Immunohistochemistry confirmed that amyloid deposits were specifically stained with an anti-apolipoprotein A-I antibody. The clinical phenotype was mainly characterized by a variable combination of kidney and liver disturbance. The occurrence of renal involvement seemed to be almost universal, although its severity varied greatly ranging from subclinical organ damage to overt, slowly progressive renal dysfunction. The renal presentation was consistent with a tubulointerstitial disease, as suggested by the findings of defective urine-concentrating capacity, moderate polyuria, negative urinalysis, and mild tubular proteinuria. Histology confirmed tubulointerstitial nephritis. Surprising, amyloid was restricted to nonglomerular regions and limited to the renal medulla. This location of apolipoprotein A-I amyloid differs sharply from other systemic amyloidoses that are mainly characterized by glomerular and vascular deposits. The tubulointerstitial nephritis as a result of hereditary apolipoprotein A-I amyloidosis is a rare disease and a challenging diagnosis to recognize. Patients who present with familial tubulointerstitial nephritis associated with liver disease require a high index of suspicion for apolipoprotein A-I amyloidosis.
Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in mild to moderately severe asthma
Authors: S. Lim
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Exhaled levels of nitric oxide (NO) are raised in asthma but the relationship between exhaled NO levels and a direct measure of airway inflammation has not been investigated in asthmatic patients treated with inhaled steroids. <h3>METHODS</h3> The relationship between exhaled NO levels, clinical measures of asthma control, and direct markers of airway inflammation were studied in patients with asthma treated with and without inhaled corticosteroids. Thirty two asthmatic patients (16 not using inhaled steroids and 16 using inhaled beclomethasone dipropionate, 400–1000 μg/day) were monitored with respect to measures of asthma control including lung function, symptom scores, medication usage, and variability of peak expiratory flow (PEF) for one month. Measurements of exhaled NO and fibreoptic bronchoscopy were performed at the end of the monitoring period. Bronchial mucosal biopsy specimens were stained with an anti-MBP antibody for quantification of eosinophils. <h3>RESULTS</h3> There was no significant difference in lung function, symptom scores, or medication usage between the two groups, but there was a significant difference in PEF variability (8.7 (1.2)% in steroid naive patients versus 13.6 (1.9)% in steroid treated patients, p&lt;0.05) and exhaled NO levels (9.9 (3.5) ppb in steroid naive patients versus 13.6 (2.0) ppb in steroid treated patients, p&lt;0.05). There was no correlation between exhaled NO and mucosal eosinophils, or between NO and conventional measures of asthma control. There was a significant correlation between mucosal eosinophils and lung function (<i>r</i> = –0.43, p&lt;0.05). <h3>CONCLUSIONS</h3> Exhaled NO levels do not reflect airway mucosal eosinophilia and these markers reflect different aspects of airway inflammation. The clinical usefulness of exhaled NO needs to be determined in prospective longitudinal studies.
Lack of Telomerase Activity in Lung Carcinoids Is Dependent on Human Telomerase Reverse Transcriptase Transcription and Alternative Splicing and Is Associated with Long Telomeres
Authors: Nadia Zaffaroni, Raffaella Villa, Ugo Pastorino, Rosalia Cirincione, Matteo Incarbone, Marco Alloisio, Maria Curto, Silvana Pilotti, Maria Grazia Daidone
Journal: Clinical Cancer Research (2005)

Preliminary evidence indicates that telomerase activity is significantly less expressed in typical carcinoids than in large cell neuroendocrine carcinomas or in small cell lung cancers. Knowledge of the mechanisms by which telomerase is differentially regulated in neuroendocrine lung tumors is important for a better understanding of the pathogenesis of these malignancies.We investigated telomerase activity in 86 neuroendocrine lung tumors and correlated the enzyme activity with the expression of the enzyme subunits [human RNA component (hTR), human telomerase reverse transcriptase (hTERT), and alternatively spliced hTERT variants], with the telomere-associated protein human protection of telomere-1, and with the telomere length pattern.A significantly (P = 0.0001) lower frequency of telomerase-positive cases was found in typical carcinoids (14%) than in large cell neuroendocrine carcinomas (87%) and small cell lung cancers (92%). hTR was constitutively expressed in all carcinoids. Telomerase-negative carcinoids were characterized by the absence of any hTERT transcript, only displayed the beta(-) alternatively spliced variant, or concomitantly expressed the alpha(+)beta(+) full-length message with different combinations of alternatively spliced variants. However, in these tumors, a more abundant level of alternatively spliced transcripts than that of the alpha(+)beta(+) full-length transcript was generally found. No significant difference was observed in human protection of telomere-1 expression between telomerase-negative and telomerase-positive carcinoids. Telomeres were significantly (P < 0.05) longer in telomerase-negative carcinoids than in telomerase-positive carcinoids (median value, 9.15 versus 4.47 kb). However, alternative lengthening of telomeres, as shown by associated promyelocytic leukemia bodies, was not observed in these tumors.Our results indicate that telomerase is repressed in most lung carcinoids and that hTERT transcription and alternative splicing play a role in such a negative regulation. Moreover, the absence of any telomerase maintenance mechanism may contribute to the favorable prognosis of this malignancy.
The Role of β7 Integrins in CD8 T Cell Trafficking During an Antiviral Immune Response
Authors: Leo Lefrançois, Christina M. Parker, Sara Olson, Werner Muller, Norbert Wagner, Lynn Puddington
Journal: The Journal of Experimental Medicine (1999)

The requirement of β7 integrins for lymphocyte migration was examined during an ongoing immune response in vivo. Transgenic mice (OT-I) expressing an ovalbumin-specific major histocompatibility complex class I–restricted T cell receptor for antigen were rendered deficient in expression of all β7 integrins or only the αEβ7 integrin. To quantitate the relative use of β7 integrins in migration in vivo, equal numbers of OT-I and OT-I-β7−/− or OT-I-αE−/− lymph node (LN) cells were adoptively transferred to normal mice. Although OT-I-β7−/− LN cells migrated to mesenteric LN and peripheral LN as well as wild-type cells, β7 integrins were required for naive CD8 T cell and B cell migration to Peyer's patch. After infection with a recombinant virus (vesicular stomatitis virus) encoding ovalbumin, β7 integrins became critical for migration of activated CD8 T cells to the mesenteric LN and Peyer's patch. Naive CD8 T cells did not enter the lamina propria or the intestinal epithelium, and the majority of migration of activated CD8 T cells to the small and large intestinal mucosa, including the epithelium, was β7 integrin–mediated. The αEβ7 integrin appeared to play no role in migration during a primary CD8 T cell immune response in vivo. Furthermore, despite dramatic upregulation of αEβ7 by CD8 T cells after entry into the epithelium, long-term retention of intestinal intraepithelial lymphocytes was also αEβ7 independent.
Localist representation can improve efficiency for detection and counting
Authors: Horace Barlow, Anthony Gardner-Medwin
Journal: Behavioral and Brain Sciences (2000)

Almost all representations have both distributed and localist aspects, depending upon what properties of the data are being considered. With noisy data, features represented in a localist way can be detected very efficiently, and in binary representations they can be counted more efficiently than those represented in a distributed way. Brains operate in noisy environments, so the localist representation of behaviourally important events is advantageous, and fits what has been found experimentally. Distributed representations require more neurons to perform as efficiently, but they do have greater versatility.
Epidermal barrier lipids in human vernix caseosa: corresponding ceramide pattern in vernix and fetal skin
Authors: P.H. Hoeger, V. Schreiner, I.A. Klaassen, C.C. Enzmann, K. Friedrichs, O. Bleck
Journal: British Journal of Dermatology (2002)

Journal Article Epidermal barrier lipids in human vernix caseosa: corresponding ceramide pattern in vernix and fetal skin Get access P.H. Hoeger, P.H. Hoeger Departments of Dermatology and Dr Peter H.Hoeger. E‐mail: hoeger@uke.uni‐hamburg.de Search for other works by this author on: Oxford Academic Google Scholar V. Schreiner, V. Schreiner Paul‐Gerson‐Unna Skin Research Center, Beiersdorf Inc., Hamburg, Germany Search for other works by this author on: Oxford Academic Google Scholar I.A. Klaassen, I.A. Klaassen Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar C.C. Enzmann, C.C. Enzmann Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar K. Friedrichs, K. Friedrichs Obstetrics/Gynaecology, University of Hamburg, Martinistr. 48, D‐20246 Hamburg, Germany Search for other works by this author on: Oxford Academic Google Scholar O. Bleck O. Bleck Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 2, 1 February 2002, Pages 194–201, https://doi.org/10.1046/j.1365-2133.2002.04584.x Published: 01 February 2002 Article history Accepted: 12 September 2001 Published: 01 February 2002
Lymphatic Neoangiogenesis in Human Kidney Transplants Is Associated with Immunologically Active Lymphocytic Infiltrates
Authors: Dontscho Kerjaschki, Heinrich M. Regele, Isabella Moosberger, Katalyn Nagy-Bojarski, Bruno Watschinger, Afschin Soleiman, Peter Birner, Sigurd Krieger, Anny Hovorka, Georg Silberhumer, Pirjo Laakkonen, Tatiana Petrova, Brigitte Langer, Ingrid Raab
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Renal transplant rejection is caused by a lymphocyte-rich inflammatory infiltrate that attacks cortical tubules and endothelial cells. Immunosuppressive therapy reduces the number of infiltrating cells; however, their exit routes are not known. Here a &gt;50-fold increase of lymphatic vessel density over normal kidneys in grafts with nodular mononuclear infiltrates is demonstrated by immunohistochemistry on human renal transplant biopsie susing antibodies to the lymphatic endothelial marker protein podoplanin. Nodular infiltrates are constantly associated with newly formed, Ki-67–expressing lymphatic vessels and contain the entire repertoire of T and B lymphocytes to provide specific cellular and humoral alloantigenic immune responses, including Ki-67<sup>+</sup> CD4<sup>+</sup> and CD8<sup>+</sup> T lymphocytes, S100<sup>+</sup> dendritic cells, and Ki-67<sup>+</sup>CD20<sup>+</sup> B lymphocytes and λ- and κ-chain-expressing plasmacytoid cells. Numerous chemokine receptor CCR7<sup>+</sup> cells within the nodular infiltrates seemed to be attracted by secondary lymphatic chemokine (SLC/CCL21) that is produced and released by lymphatic endothelial cells in a complex with podoplanin. From these results, it is speculated that lymphatic neoangiogenesis not only contributes to the export of the rejection infiltrate but also is involved in the maintenance of a potentially detrimental alloreactive immune response in renal transplants and provides a novel therapeutic target.
Addition of Salmeterol versus Doubling the Dose of Beclomethasone in Children with Asthma
Authors: ANJA A. P. H. VERBERNE, CHRIS FROST, ERIC J. DUIVERMAN, MARION H. GROL, KAREL F. KERREBIJN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Studies in adults revealed that addition of salmeterol to a moderate dose of inhaled corticosteroid resulted in better symptom control and higher PEF compared with doubling the dose of inhaled corticosteroid. The aim of this three group study was to compare the effects of a moderate dose of beclomethasone, the same dose of beclomethasone with salmeterol, and a doubling dose of beclomethasone on lung function and symptoms in children with moderate asthma. A total of 177 children already treated with inhaled corticosteroids, were randomized in a double-blind parallel study either to salmeterol 50 μ g twice daily (BDP400 + salm), beclomethasone 200 μ g twice daily (BDP800), or placebo (BDP400) in addition to beclomethasone 200 μ g twice daily. No significant differences between groups were found in FEV1, PD20 methacholine, symptom scores, and exacerbation rates after 1 yr. Salmeterol resulted in slightly better PEF in the first months of treatment. FEV1, and PD20 methacholine significantly improved in all groups. After 1 yr mean changes in FEV1, percent predicted were 4.3% (95% CI 1.3; 7.2), 5.8% (95% CI 2.9; 8.7), and 4.3% (95% CI 2.1; 6.5) for BDP400 + salm, BDP800, and BDP400, respectively. Changes in airway responsiveness were 0.60 (95% CI 0.05; 1.14), 1.30 (95% CI 0.73; 1.87), and 0.80 (95% CI 0.33; 1.27) doubling doses. Growth was significantly slower in the BDP800 group. We conclude that no additional benefit was found of adding either salmeterol or more beclomethasone to a daily dose of 400 μ g beclomethasone in this group of children with excellent compliance of medication.
Complement-fixing ability of antinuclear factors. Studies in adult and juvenile rheumatoid arthritis and systemic lupus erythematosus.
Authors: P M Cossio, R M Arana, O G Morteo, O Hubscher, E B Roux
Journal: Annals of the Rheumatic Diseases (1971)

Fluorescein conjugated antiglobulins are prepared according to the specifications for the production of anti-human IgG conjugates set forth at the London Round Table Conference on Standardization in Immunofluorescence, October, 1968.t Laboratoire d'Immunochimie, Institut de Recherches sur les Maladies du Sang, Paris.The antiserum was prepared by immunizing rabbits with human IgA myeloma proteins and labelled with fluorescein isothiocinate according to the method of Nairn (1968).The antiserum was already specific for a chain.
Quantification of Plasma β-Catenin mRNA in Colorectal Cancer and Adenoma Patients
Authors: Sze Chuen Cesar Wong, Siu Fong Elena Lo, Moon Tong Cheung, Kai On Enders Ng, Chun Wah Tse, Bo San Paul Lai, King Chung Lee, Y. M. Dennis Lo
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Colorectal cancer is an important cause of cancer deaths. Here, we focused our investigation on the β-catenin gene which is implicated in colorectal carcinogenesis and tested whether β-catenin mRNA is detectable in the plasma of colorectal carcinoma and adenoma patients using quantitative reverse transcriptase-PCR. Experimental Design: Plasma β-catenin mRNA was measured from 58 colorectal carcinoma patients, 49 colorectal adenoma patients, and 43 apparently normal subjects using intron-spanning primers and Taqman probes. Five clinicopathological parameters were studied and correlated with plasma β-catenin mRNA concentration. Additionally, 19 colorectal carcinoma patients after tumor removal were also recruited for plasma β-catenin mRNA measurement to further demonstrate the clinical usefulness of this test. Results: β-catenin mRNA was detected with median concentrations of 8737 (range: 1480–933,100), 1218 (range: 541–2,254) and 291 (range: 0–1,366) copies/ml plasma in colorectal carcinoma, colorectal adenoma, and apparently normal subjects, respectively. Statistical analysis demonstrated that plasma β-catenin mRNA concentration was correlated to tumor stage but not sex, age, lymph node status, and degree in differentiation. Moreover, plasma β-catenin mRNA concentration decreased significantly after tumor removal in 16 of 19 (84%) colorectal carcinoma patients. Conclusions: We conclude that plasma β-catenin mRNA may potentially serve as a marker for colorectal cancer.
Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans
Authors: Lise Bankir, Sandrine Fernandes, Pascale Bardoux, Nadine Bouby, Daniel G. Bichet
Journal: Journal of the American Society of Nephrology (2005)

In addition to its effect on water permeability, vasopressin, through its V2 receptors (AVPR2), stimulates Na reabsorption in the collecting duct by increasing the activity of the amiloride-sensitive sodium channel ENaC. This study evaluated whether dDAVP (a potent AVPR2 agonist) reduces sodium excretion in healthy humans (n = 6) and in patients with central (C; n = 2) or nephrogenic (N) diabetes insipidus (DI) as a result of mutations of either the aquaporin 2 gene (AQP2; n = 3) or AVPR2 (n = 10). dDAVP was infused intravenously (0.3 μg/kg body wt in 20 min), and urine was collected for 60 min before (basal) and 150 min after the infusion. dDAVP markedly reduced both urine flow rate and sodium excretion in healthy individuals. A reduction in sodium excretion was also observed in CDI and NDI-AQP2 patients but not in NDI-AVPR2 patients. The magnitude of the fall in sodium excretion correlated with the rise in urine osmolality and the fall in urine output but not with the simultaneously observed fall in mean BP. These results suggest that the dDAVP-induced antinatriuresis is due to a direct V2 receptor–dependent stimulation of sodium reabsorption in the collecting duct and is not secondary to a hemodynamic effect. In conclusion, this study reveals a potent V2-dependent antinatriuretic effect of vasopressin in humans. The possibility that an inappropriate stimulation of ENaC by vasopressin might lead to significant sodium retention in chronic situations remains to be determined.
Synergistic Tumorigenic Effect of Procarbazine and Ionizing Radiation in (BALB/c × DBA/2)F1 Mice23
Authors: James C. Arseneau, Edward Fowler, Richard F. Bakemeier
Journal: JNCI Journal of the National Cancer Institute (1977)

Female (BALB/c × DBA/2)F1 (CD2F1) mice were treated with procarbazine (PCB) and ionizing radiation at different times to determine whether any synergistic carcinogenic effect could be demonstrated with the combined treatment. The incidence of pulmonary adenomas in groups of mice receiving both PCB and radiation increased significantly, when compared with mice given PCB alone. The incidence of thymomas also increased significantly in groups of mice given PCB 3 days before or after radiation treatment. Two cases of adenocarcinoma apparently arising from the lacrimal gland were also observed in mice from the groups receiving the combined treatment. This tumor had not previously been associated with PCB administration in mice. The results of this experiment indicated a potentiation of the tumorigenic action of PCB by ionizing radiation in CD2F1 mice.
The Counseling African Americans to Control Hypertension Study and Ways to Enhance the Next Wave of Behavioral Interventions
Authors: Kevin G. Volpp
Journal: Circulation (2014)

T he Counseling African Americans to Control Hypertension (CAATCH) study by Ogedegbe et al 1 in this issue of Circulation represents a carefully done study with many strengths.It recognized that blacks have the highest prevalence of hypertension 2 and that poor hypertension-related outcomes explain most of the racial gap in mortality between blacks and whites. 3It represents the largest practice-based implementation trial to date of a multilevel, evidence-based intervention targeted at blood pressure (BP) control in hypertensive blacks in community health centers, where many lowincome Americans receive their care.In addition, although the individual components of CAATCH (patient education, home BP monitoring, continuing medical education, physician chart audit, and feedback) have proven efficacious and effective for improving BP control, 1 the effectiveness of a combined approach in community health centers has not been rigorously evaluated.The study was adequately powered to detect a difference of ≥4 mm Hg for systolic BP and 3 mm Hg for diastolic BP at 12 months between intervention and control arms assuming a 15% attrition rate.However, the intervention did not have any impact in improving BP control relative to a randomly selected control group.This disappointing result highlights the challenge of creating successful practice-based interventions in the settings where implementation at scale is possible.The lack of success begs for closer examination.
Balancing reactivity against selectivity: The evolution of protein S-nitrosylation as an effector of cell signaling by nitric oxide
Authors: B DERAKHSHAN, G HAO, S GROSS
Journal: Cardiovascular Research (2007)

Produced by the action of lightning in the atmosphere of the pre-biotic earth, nitric oxide (NO) is a free radical molecule that provided the major nitrogen source for development of life. Remarkably, when atmospheric sources of NO became restrictive, organisms evolved the capacity for NO biosynthesis and NO took on bioregulatory roles. We now recognize NO as an ancestral regulator of diverse and important biological functions, acting throughout the phylogenetic tree. In mammals, NO has been implicated as a pivotal regulator of virtually every major physiological system. The bioactivities of NO, and reactive species derived from NO, arise predominantly from their covalent addition to proteins. Importantly, S-nitrosylation of protein cysteine (Cys) residues has emerged as a preeminent effector of NO bioactivity. How and why NO selectively adds to particular Cys residues in proteins is poorly understood, yet fundamental to how NO communicates its bioactivities. Also, evolutionary pressures that have shaped S-nitrosylation as a biosignaling modality are obscure. Considering recently recognized NO signaling paradigms, we speculate on the origin of NO signaling in biological systems and the molecular adaptations that have endowed NO with the ability to selectively target a subset of protein Cys residues that mediate biosignaling.
Calreticulin, a Peptide-binding Chaperone of the Endoplasmic Reticulum, Elicits Tumor- and Peptide-specific Immunity
Authors: Sreyashi Basu, Pramod K. Srivastava
Journal: The Journal of Experimental Medicine (1999)

Calreticulin (CRT), a peptide-binding heat shock protein (HSP) of the endoplasmic reticulum (ER), has been shown previously to associate with peptides transported into the ER by transporter associated with antigen processing (Spee, P., and J. Neefjes. 1997. Eur. J. Immunol. 27: 2441–2449). Our studies show that CRT preparations purified from tumors elicit specific immunity to the tumor used as the source of CRT but not to an antigenically distinct tumor. The immunogenicity is attributed to the peptides associated with the CRT molecule and not to the CRT molecule per se. It is further shown that CRT molecules can be complexed in vitro to unglycosylated peptides and used to elicit peptide-specific CD8+ T cell response in spite of exogenous administration. These characteristics of CRT closely resemble those of HSPs gp96, hsp90, and hsp70, although CRT has no apparent structural homologies to them.