tbuckley/cabot-search huggingface dataset:
Effect of a Mouse Mammary Tumor Virus-Derived Protein Vaccine on Primary Tumor Development in Mice 2
Authors: Paula Creemers, Jacqueline Ouwehand, Peter Bentvelzen
Journal: JNCI Journal of the National Cancer Institute (1978)

The vaccines used in this study were derived from purified murine mammary tumor virus (MuMTV) preparations. Approximately 60% of the protein fractions consisted of the major viral membrane glycoprotein gp52. Inoculation sc of 10 microgram MuMTV-S-derived vaccine significantly delayed the appearance of primary mammary tumors in GR and BALB/cfC3H mice (strains with high incidences of mammary cancer); in BALB/c and C3Hf mice, which have a moderate tumor incidence at an advanced age, this treatment resulted in a slight and substantial acceleration, respectively, of primary tumor development. The induced cellular immune reactivity for vaccination, as measured with the in vivo Winn test and the in vitro leukocyte adherence inhibition assay, was strongest in the GR strain as compared to the BALB/c strain. The titer of antibodies to tumor cells, as estimated by membrane immunofluorescence, was also higher in the GR strain. In BALB/cfC3H mice, the influence of different vaccination schemes with an MuMTV-O-derived protein vaccine on primary tumor development was studied. Before sc injection, the vaccine was precipitated on alum. A dose of 10 microgram vaccine resulted in a 61% decrease in tumor incidence. Two or five additional booster injections with 1 microgram protein vaccine had no beneficial effect, although the amount of antibody measured was increased after boosting.
Discordance Between K-<i>ras</i> Mutations in Bone Marrow Micrometastases and the Primary Tumor in Colorectal Cancer
Authors: Silvia Tórtola, Ralf Steinert, Marco Hantschick, Miguel A. Peinado, Ingo Gastinger, Peter Stosiek, Hans Lippert, Werner Schlegel, Marc A. Reymond
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To study bone marrow micrometastases from colorectal cancer patients for the presence of K-ras mutations and to compare their genotype with that of the corresponding primary tumor. PATIENTS AND METHODS: Bilateral iliac crest aspiration was performed in 51 patients undergoing surgery for colorectal cancer, and bone marrow micrometastases were detected by immunohistochemistry. The presence of K-ras mutations was determined by single-strand conformation polymorphism analysis on both primary tumors and paired bone marrow samples and was confirmed by sequencing. RESULTS: In six patients with primary tumor mutations, it was possible to amplify a mutated K-ras gene also from the bone marrow sample. In three of those patients the pattern of K-ras mutations differed between both samples, in two patients the mutation was identical between the bone marrow and its primary tumor, and in one patient the same mutation plus a different one were found. Fifteen of 17 K-ras mutations found in primary tumors were located in codon 12, whereas in bone marrow, five of seven mutations were found in codon 13 (P = .003). CONCLUSION: Our results demonstrate that, at least for K-ras mutations, disseminated epithelial cells are not always clonal with the primary tumor and they question the malignant genotype of bone marrow micrometastases. They also indicate that different tumoral clones may be circulating simultaneously or sequentially in the same patient. Analysis of the type of mutations suggests that cell dissemination might be an early event in colorectal carcinogenesis.
The clinical and genetic factors for predicting the response to inhaled corticosteroids
Authors: Hiroyuki Nagase, Naomi Tsurikisawa, Eiko Matsui, Naomi Kondo, Kazuo Akiyama, Ken Ohta
Journal: European Respiratory Journal (2014)

[Background]  A part of asthma patients does not respond well to inhaled corticosteroids (ICS) and the benefit by high-dose ICS is limited in such patients. The aim of this study is to establish the clinical or genetic factor for predicting the response to ICS treatment.   [Method]  Patients treated only by ICS for more than 6 months were enrolled and classified into responder group (R group, n=30) if FEV1 improvement ≥ 5% and nonresponder group (NR group, n =40, FEV1 improvement   [Results]  In R group, peripheral blood eosinophil% (R: NR = 7.5: 4.3%) and serum total IgE level (550.4: 497.1 U/ml) was significantly higher as compared to NR group. R group also showed significantly lower %VC (97.5: 114.8%), %FEV1.0 (77.9: 101.3%), FEV1.0% (67.5:76.4%) and higher bronchial hyperresponsiveness. Bronchial reversibility test was available in 30 patients (R: n=11, NR: n=19) and reversibility was significantly higher in R group (15.9: 5.4%). By logistic multivariate analysis for those 30 patients, bronchial reversibility was significantly related to ICS response. SNP in IFNγR1 L467P was also related to ICS response. Post /Pre FEV1 ratio was significantly higher in homo/hetero group as compared to wild group (140.2 vs 108.8%).   [Conclusion]  Pretreatment bronchial reversibility was identified as a prediction factor for ICS response. It has been reported that SNP in IFNγR1 is associated with allergic diseases and serum IgE level and the SNP might be potentially related to ICS response.
Organic anion secretion in polycystic kidney disease.
Authors: G A Tanner, N Gretz, Y Shao, A P Evan, M Steinhausen
Journal: Journal of the American Society of Nephrology (1997)

This study examined whether organic anion secretion contributes to fluid accumulation in cysts in polycystic kidney disease. Clearance and micropuncture studies were done on young (7 to 16 wk old), mostly male, heterozygous Han:SPRD cystic rats and healthy control littermate rats. Heterozygous Han:SPRD rats manifest a slowly progressive autosomal dominant polycystic kidney disease that closely resembles the human disorder. Left kidney GFR (polyfructosan clearance), in microl/min per 100 g body wt, averaged 331 +/- 36 (SD) in seven healthy rats and 278 +/- 75 in seven cystic rats. The maximal rate of p-aminohippurate (PAH) secretion, in micromol/min per 100 g body wt, averaged 0.94 +/- 0.24 in healthy rats and 0.83 +/- 0.11 in cystic rats. In these young rats, there were no significant differences in GFR or the maximal rate of PAH secretion despite the presence of cystic disease. Using fluorescence microscopy, it was found that 27 of 29 proximal cysts secreted sulfonefluorescein, an organic anion transported by the PAH system. Transmission electron micrographs of superficial cysts that had secreted sulfonefluorescein demonstrated the presence of both normal-appearing and poorly differentiated proximal tubule cells. Segments of superficial proximal convoluted tubules or cysts, isolated by upstream and downstream wax blocks, failed to accumulate fluid when PAH was infused intravenously. With the stationary microperfusion technique, PAH secretion by both normal and cystic nephrons was demonstrated. It is concluded that most proximal cystic epithelia retain the ability to secrete organic anions. Secretion of organic anions, however, does not appear to contribute in any substantial way to fluid accumulation in cysts in the rat kidney.
Study of psychiatric comorbidities in patients with bronchial asthma
Authors: Essam Gouda, Mohamed Zidan, Ghada Abdelhady, Mervat Fatthy
Journal: European Respiratory Journal (2014)

Introduction:  Patients with asthma tend to have anxiety and depression. The presence of psychological morbidity is, however, frequently underestimated, so under diagnosed and under treated.  Objective:  To evaluate some psychiatric comorbidities (depression and anxiety) in asthmatic patient and to examine the possible associations with the demographic and clinical characteristics as well as the level of control of asthma in those patients.  Methods:  One hundred asthmatic patients were enrolled in this study. The level of control was assessed by Asthma Control Questionnaire (ACQ), Anxiety was assessed by The Generalized Anxiety Disorder Scale (GADS). Depression was assessed by The Hamilton Depression Rating Scale (HAM-D).  RESULTS:  The prevalence of anxiety was significantly higher among patients with uncontrolled asthma especially moderate and severe anxiety (67.1% in poorly controlled asthma group and 11.1% in controlled asthma group but 8.5% in poorly controlled asthma group and 0.0 % in controlled asthma group respectively with p Conclusion:  Anxiety and depression adversely affect asthma control and quality of life, raising the possibility that treating these psychological comorbidities could improve asthma control and quality of life.
Lymphocyte Reactivity in Normal and Malignant Cell Proliferation Against a Phylogenetically Conserved Antigen in Fetal Extracts&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G Pasternak, B Schlott, G Gryschek, S Albrecht, J Reinhöfer, E Matthes, B von Broen
Journal: JNCI Journal of the National Cancer Institute (1984)

Lymphocyte reactivity to 3-M KCl extracts from fetuses of different species of origin was shown by the macrophage electrophoretic mobility (MEMB) and/or the leukocyte migration inhibition tests in tumor-bearing mice and humans. In chemical carcinogenesis, reactivity was detectable before tumors developed. Six weeks after sc injection of 1,000 micrograms benzo[a]pyrene [(BP) CAS: 50-32-8] into XVII/Bln mice, the MEMB test became positive. The latent period was 15 weeks after 1.0 micrograms BP, indicating a dose-response relationship of the phenomenon. Painting of mouse skin with 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6], croton oil (CAS: 8001-28-3), or benzene (CAS: 71-43-2) had the same sensitizing effect as BP. In contrast to the strong carcinogens BP and DMBA that caused lymphocyte reactivity to persist until tumors developed, benzene and the promoter croton oil induced only a transient effect. Termination of treatment abolished reactivity within 12 weeks. Lymphocyte reactivity to fetal extract in normal cell proliferation was evident from the fact that two-thirds-hepatectomized rats and BCG-treated mice became MEMB-positive. In hepatectomized rats the effect was reversible according to the completion of liver regeneration. Lymphocytes from tumor-bearing mice reacted with mouse and human fetal extract as well as with extracts from different developmental stages of frogs and fish. Fetal extracts were assumed to contain a phylogenetically conserved antigen.
Crypt Cell Antigen Expression in Human Colon Tumor Cell Lines: Analysis With a Panel of Monoclonal Antibodies to CaCo-2 Luminal Membrane Components2
Authors: Andrea Quaroni
Journal: JNCI Journal of the National Cancer Institute (1986)

Twenty BALB/c mouse monoclonal antibodies to surface membrane components of confluent CaCo-2 cells were used to study the expression of small intestine markers in cultured human colon tumor cells. The antigens recognized by 15 of these antibodies were identified as membrane proteins of relatively high molecular weight, one of them corresponding to the single-chain precursor of sucrase-isomaltase. By immunofluorescence, 14 antibodies were found to stain the small intestine epithelial cells, and various distinctive patterns of antigen distribution in human jejunum were observed. Five antibodies stained exclusively the crypt cells, 3 the luminal membranes of the absorptive villus cells, and 4 the entire epithelium. In contrast, only 4 antibodies stained normal human colon tissue. The different antigens defined by this panel of monoclonal antibodies showed great variability in their expression in 14 human intestinal tumor cell lines tested. These results demonstrated a surprising similarity between many colon tumor cell lines and intestinal crypt cells and identified a set of new intestinal cell surface markers that can be used to identify and characterize intestinal tumor cells in vivo and in culture.
Genetics and pulmonary medicine bullet 10: Genetic epidemiology of pulmonary function
Authors: Y. Chen
Journal: Thorax (1999)

Respiratory diseases are major threats to human health.1 It is believed that chronic obstructive pulmonary disease (COPD) is both environmental and genetic2 3; however, specific genetic factors in the development of COPD have not been clearly identified, except for protease inhibitor types. Alpha1-antitrypsin deficiency is rare in the general population4 5 and accounts for less than 2% of the cases of COPD.6 7 The molecular genetics of COPD has recently been reviewed by Barnes.8 

Pulmonary function measures are the most important phenotypes of COPD. The respiratory muscles, the thorax, and the lungs are the components of the ventilatory apparatus which can be evaluated by appropriate function tests.9 The dynamic functional capacity of the ventilatory apparatus can be assessed by the volume-time or flow-volume manoeuvres. Airflow rates and volumes inhaled or exhaled over specific time intervals provide information on the flow resistive properties of the airways.10 These pulmonary function measures predict the development of lung diseases11-13 and overall mortality.14-18 While the environmental determinants of pulmonary function have been extensively studied—for example, smoking and ambient air pollution—the genetic determinants have recently received increasing attention. Genetic epidemiological studies of pulmonary function are of potential importance in understanding normal pulmonary function and the aetiology and prevention of COPD and other respiratory diseases. This paper reviews the familial aggregation and segregation of pulmonary function and presents evidence for different influences of heredity on airway function, lung volume, and airway-parenchymal dysanapsis (relative airway size to lung size). Some methodological issues related to segregation analysis are also discussed.

### FAMILY STUDIES

A number of family studies have provided evidence for familial resemblance of pulmonary function measures.19-30Studies have consistently shown significant parent-offspring and sibling-sibling correlations in lung volume and flow rate measures (table 1). Most studies found …
S<scp>ELECTIVITY IN</scp>N<scp>EUROTROPHIN</scp>S<scp>IGNALING</scp>: Theme and Variations
Authors: Rosalind A. Segal
Journal: Annual Review of Neuroscience (2003)

▪ Abstract Neurotrophins are a family of growth factors critical for the development and functioning of the nervous system. Although originally identified as neuronal survival factors, neurotrophins elicit many biological effects, ranging from proliferation to synaptic modulation to axonal pathfinding. Recent data indicate that the nature of the signaling cascades activated by neurotrophins, and the biological responses that ensue, are specified not only by the ligand itself but also by the temporal pattern and spatial location of stimulation. Studies on neurotrophin signaling have revealed variations in the Ras/MAP kinase, PI3 kinase, and phospholipase C pathways, which transmit spatial and temporal information. The anatomy of neurons makes them particularly appropriate for studying how the location and tempo of stimulation determine the signal cascades that are activated by receptor tyrosine kinases such as the Trk receptors. These signaling variations may represent a general mechanism eliciting specificity in growth factor responses.
V/Q and alveolar gas exchange in pulmonary sarcoidosis
Authors: A Eklund, L Broman, M Broman, A Holmgren
Journal: European Respiratory Journal (1989)

Eleven patients with pulmonary sarcoidosis of type II or III were investigated with regard to regional distribution of ventilation and perfusion (V/Q), alveolar gas exchange and diffusion limit at rest and during exercise. Lung volumes were 50-65% of normal values. Flow-volume curves indicated obstructive changes. The transfer factor was 75% (range 16-120%) of predicted. Perfusion scintigraphy showed marked defects in 7 out of 11 patients. Radiospirometry showed matching ventilation and perfusion defects and washout of xenon was prolonged. There was a venous admixture at rest of 9%. Arterial oxygen tension (Pao2) averaged 9.7 kPa. V/Q analyses indicated the presence of a small shunt (1%), regions with low V/Q in 4 out of 11 patients, regions with high V/Q in 5 out of 11 patients and increased wasted ventilation. At rest measured Pao2 was lower (0.6 kPa) than predicted from the V/Q distribution. During mild supine exercise causing significant dyspnoea, pulmonary vascular resistance rose to abnormal values, 5.2 mmHg.l.-1 min-1.m2 BSA. The venous admixture decreased to 5.4%. The shunt was unchanged, as was the perfusion of regions with low V/Q. The regions with abnormally high V/Q disappeared. Measured Pao2 decreased to 9.1 kPa, while calculated Pao2 remained unchanged. Thus the P(A-a)o2 at rest (4.2 kPa) was 70% caused by shunt and V/Q mismatch. During exercise alveolar-arterial pressure difference for oxygen measured P(A-a)o2 rose further to 5.1 kPa, while calculated P(A-a)o2 remained unchanged and was only 50% caused by shunt and V/Q disturbances. The difference between calculated and measured Pao2 indicated significant diffusion limitation both at rest and during mild exercise.
Chronic parathyroid hormone excess in vivo increases resting levels of cytosolic calcium in brain synaptosomes
Authors: M Smogorzewski, P Koureta, G Z Fadda, A F Perna, S G Massry
Journal: Journal of the American Society of Nephrology (1991)

It has been suggested that excess parathyroid hormone (PTH) in chronic renal failure (CRF) or chronic administration of PTH to normal rats caused derangements in norepinephrine and phospholipid metabolism of brain synaptosomes, because of an increase in their resting levels of cytosolic calcium which may induce a decrease in synaptosomal content of ATP. In the study presented here, the resting levels of cytosolic calcium in brain synaptosomes were measured in six groups of rats including: (1) normal rats; (2) rats with CRF of 21-days duration; (3) normocalcemic parathyroidectomized rats with CRF of 21-days duration; (4) rats with CRF of 21-days duration treated with verapamil from day 1 of CRF; (5) normal rats treated with verapamil for 21 days; and (6) normal rats treated with PTH for 21 days. Resting levels of cytosolic calcium of brain synaptosomes of CRF rats (437 +/- 18.0 nM) and normal rats treated with PTH (428 +/- 5.6 nM) were significantly (P less than 0.01) higher than those of normal rats (345 +/- 9.0 nM), normal rats treated with verapamil (354 +/- 8.7 nM), CRF rats treated with verapamil (361 +/- 12.9 nM), or CRF-parathyroidectomized rats (363 +/- 8.2 nM). There were no significant differences between the values of the last three groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetics of Susceptibility of Rats to Trigeminal Schwannomas Induced by Neonatal Administration of &lt;italic&gt;N&lt;/italic&gt;-Ethyl-&lt;italic&gt;N&lt;/italic&gt;-nitrosourea&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: M Naito, A Ito, H Aoyama
Journal: JNCI Journal of the National Cancer Institute (1985)

A genetic analysis was done on the induction of trigeminal schwannomas by N-ethyl-N-nitrosourea [(ENU) CAS: 759-73-9] in susceptible LE rats, resistant WF rats, and their F1, F2, and reciprocal backcross hybrids. Both sexes of all strains were given a neonatal sc injection of 40 mg ENU/kg body weight and were sacrificed at 6 months after treatment. Many neurogenic tumors were induced in the central nervous system of all strains of rats. However, the incidence of trigeminal schwannomas in LE rats was 93% in males and 86% in females, whereas in WF rats the incidence was 24% in males and 20% in females. F1 and F2 hybrids showed an intermediate susceptibility (62 and 82% in F1 males, 79 and 86% in F2 males, 26 and 38% in F1 females, and 65 and 77% in F2 females). The incidence in hybrids backcrossed to LE was high (90 and 100% in males and 77 and 83% in females), and the incidence in hybrids backcrossed to WF was low (35 and 38% in males and 11 and 7% in females). The findings suggest that susceptibility to the induction of trigeminal schwannomas by ENU does not result from the expression of genes that are simple dominant or recessive genes. A genetic model involving three independently segregating loci may explain the experimental results. In all strains of rats, particularly the F1 hybrids, males were more susceptible than females to the induction of trigeminal schwannomas by ENU.
Mutations in the Chloride Channel Gene CLCNKB as a Cause of Classic Bartter Syndrome
Authors: MARTIN KONRAD, MARTIN VOLLMER, HENNY H. LEMMINK, LAMBERTUS P. W. J. VAN DEN HEUVEL, NIKOLA JECK, ROSA VARGAS-POUSSOU, ALICIA LAKINGS, RAINER RUF, GEORGES DESCHE[Combining Circumflex Accent]NES, CORINNE ANTIGNAC, LISA GUAY-WOODFORD, NINE V. A. M. KNOERS, HANNSJO[Combining Diaeresis]RG W. SEYBERTH, DELPHINE FELDMANN, FRIEDHELM HILDEBRANDT
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Inherited hypokalemic renal tubulopathies are differentiated into at least three clinical subtypes: ( 1 ) the Gitelman variant of Bartter syndrome (GS); ( 2 ) hyperprostaglandin E syndrome, the antenatal variant of Bartter syndrome (HPS/aBS); and ( 3 ) the classic Bartter syndrome (cBS). Hypokalemic metabolic alkalosis and renal salt wasting are the common characteristics of all three subtypes. Hypocalciuria and hypomagnesemia are specific clinical features of Gitelman syndrome, while HPS/aBS is a life-threatening disorder of the newborn with polyhydramnios, premature delivery, hyposthenuria, and nephrocalcinosis. The Gitelman variant is uniformly caused by mutations in the gene for the thiazide-sensitive NaCl-cotransporter NCCT (SLC12A3) of the distal tubule, while HPS/aBS is caused by mutations in the gene for either the furosemide-sensitive NaK-2Cl-cotransporter NKCC2 (SLC12A1) or the inwardly rectifying potassium channel ROMK (KCNJ1) . Recently, mutations in a basolateral chloride channel CLC-Kb (CLCNKB) have been described in a subset of patients with a Bartter-like phenotype typically lacking nephrocalcinosis. In this study, the screening for CLCNKB mutations showed 20 different mutations in the affected children from 30 families. The clinical characterization revealed a highly variable phenotype ranging from episodes of severe volume depletion and hypokalemia during the neonatal period to almost asymptomatic patients diagnosed during adolescence. This study adds 16 novel mutations to the nine already described, providing further evidence that mutations in the gene for the basolateral chloride channel CLC-Kb are the molecular basis of classic Bartter syndrome. Interestingly, the phenotype elicited by CLCNKB mutations occasionally includes HPS/aBS, as well as a Gitelman-like phenotype.
Infectious complications in patients undergoing unrelated donor bone marrow transplantation: experience from a single institution
Authors: S. Saavedra, I. Jarque, G.F. Sanz, F. Moscardó, C. Jiménez, G. Martín, G. Plumé, A. Regadera, J. Martínez, J. De la Rubia, B. Acosta, J. Pemán, C. Pérez-Bellés, M. Gobernado, M.A. Sanz
Journal: Clinical Microbiology and Infection (2002)