tbuckley/cabot-search huggingface dataset:
ON THE NYMPH AND PROSOPON OF THE TSUTSUGAMUSHI, LEPTOTROMBIDIUM AKAMUSHI, N. SP. (TROMBIDIUM AKAMUSHI BRUMPT), CARRIER OF THE TSUTSUGAMUSHI DISEASE
Authors: Mataro Nagayo, Yoneji Miyagawa, Tokushiro Mitamura, Arao Imamura
Journal: The Journal of Experimental Medicine (1917)

Nomenclature. As mentioned above, the prosopon and the nymph of the tsutsugamushi have many characteristics which distinguish it from the other trombidia. These are the pale color and small size of the body, delicacy of the skin, the conspicuous constriction between the cephalothoracic region and the abdomen, rudimentary eyes and tracheal openings, absence of tracheal capillaries, etc. The fact that the thumb or the appendage of the palpus does not start from the side of the fourth joint of the latter but from its end, is another charac teristic which does not occur in other trombidia. From the biological point of view two facts should be mentioned; i.e., the adult female does not deposit eggs in heaps, and in contrast to those of other species, the larvaae hatch out all through the year and feed on mammals. From these characteristics running through all the stages of development, we believe that we are justified in claiming a new genus for the tsutsugamushi. We therefore propose to change the scientific name given to this mite by Brumpt in 1910, Trombidium akamushi, and to introduce instead, according to the suggestion of Drs. Goto and Watase, the name Leptotrombidium akamushi. Determinaton of Leptotrombidium akamushi, N. Sp. Prosopon and Nymph. 1. Pale color. 2. Delicacy of the skin. 3. Distinct constriction between the cephalothoracic region and the abdomen. 4. Rudimentary, sessile eyes. 5. Indistinctnes of tracheal openings. 6. Absence of tracheal capillaries. 7. Crista abruptly widened at the end. 8. One palpal claw. Larva. 1. One scutum. 2. Round pinacles. 3. Legs, six joints, not counting the coxa. 4. Haris on the coza: one each on Joints 1, 2, and 3. 5. Hairs on the scutum, including two tactile hairs, seven; one is in the median line. Specific Determination of Leptotrombidium akamushi, N. Sp. (Trombidium akamushi Brumpt, 1910). Prosopon. 1. Small size 2. Three pairs of sucking discs on the external genitalia. 3. Hairs of the body feathered, club-shaped at the end, and the colorless. 4. The appendage of the palpus tapes distinctly towards the end. Nymph. 1. The size of the body is smaller thant that of the prosopon. 2. Two pairs of sucking discs on the external genitalia. There are no other distinct differences in the external morphology between the proposon and the nymph. Larva. 1. The color of the body is orange-red, but becomes paler after sucking on mammals. 2. The hairs of the body average 110 to 120 in number. 3. One pair of double eyes. 4. The sucking tube is visible when feeding on mammals (Hayashi). 5. The salivary gland is relatively large (Kawamura and Komagata). 6. The number and arrangemetn of the hairs on the legs and mouth parts correspond to the description given by Hirst. 7. The larvae are found all through the year. 8. The larva is the carrier of tsutsugamushi disease in man.
Microenvironmental Genomic Alterations and Clinicopathological Behavior in Head and Neck Squamous Cell Carcinoma
Authors: Frank Weber, Yaomin Xu, Li Zhang, Attila Patocs, Lei Shen, Petra Platzer, Charis Eng
Journal: JAMA (2007)

Carcinogens associated with head and neck squamous cell carcinoma (SCC) genesis should inflict genomic alterations not only on the epithelium but also the mesenchyme of the aerodigestive tract. Therefore, the apparently nonmalignant stroma surrounding the tumor epithelium can acquire genomic alterations and contribute to cancer initiation and progression.To determine compartment-specific loci of loss of heterozygosity or allelic imbalance (LOH/AI) and to identify which genomic alterations restricted to the stroma cell population contribute to aggressiveness of head and neck SCC disease.Tumor epithelium and surrounding stroma were isolated from 122 US patients with oral cavity and oropharyngeal or hypopharyngeal SCC and subjected to whole-genome LOH/AI analysis using 366 microsatellite markers. Samples, collected between 2001 and 2004, were pulled and transferred in batches of 10 to 30 between 2002 and 2005. Laser capture microdissection DNA extraction and technical genotyping occurred on a rolling model between 2002 and November 2005.Compartment-specific frequency and distribution of LOH/AI were determined, and hot spots of genomic alterations identified. Compartment-specific LOH/AI events were correlated with presenting clinicopathologic characteristics.Tumor-associated stroma of head and neck SCC from smokers were found to have a high degree of genomic alterations. A correlation between tumor aggressiveness could be found for a specific set of 5 loci. Three stroma-specific loci (D4S2417, D3S360, and D19555) were associated with tumor size (pT) and regional nodal metastases (pN). Furthermore, 2 epithelial-specific LOH/AI hot spots were positively correlated with pN status and clinical stage.Stroma-specific genetic alterations are associated with smoking-related head and neck SCC genesis. These findings suggest novel prognostic or diagnostic biomarkers and identify potential new molecular targets for therapeutic and preventive intervention.
The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity
Authors: Benoit Viollet, Fabrizio Andreelli, Sebastian B. Jørgensen, Christophe Perrin, Alain Geloen, Daisy Flamez, James Mu, Claudia Lenzner, Olivier Baud, Myriam Bennoun, Emmanuel Gomas, Gaël Nicolas, Jørgen F.P. Wojtaszewski, Axel Kahn, David Carling, Frans C. Schuit, Morris J. Birnbaum, Erik A. Richter, Rémy Burcelin, Sophie Vaulont
Journal: Journal of Clinical Investigation (2003)

AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene was inactivated. AMPKalpha2(-/-) mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKalpha2(-/-) pancreatic islets, glucose- and L-arginine-stimulated insulin secretion were not affected. AMPKalpha2(-/-) mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKalpha2(-/-) muscles. These data indicate that AMPKalpha2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKalpha2(-/-) mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKalpha2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity.
NHS pay rise may be capped below 1% for next few years
Authors: A. O'Dowd
Journal: BMJ (2010)

<h3>Background:</h3> Angiopoietin-2 and vascular endothelial growth factor (VEGF) may impair vascular barrier function while angiopoietin-1 may protect it. It was hypothesised that circulating angiopoietin-2 is associated with pulmonary permeability oedema and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) during septic or non-septic critical illness. <h3>Methods:</h3> Plasma levels of angiopoietin-1 and angiopoietin-2 were measured in mechanically ventilated patients (24 with sepsis, 88 without sepsis), together with the pulmonary leak index (PLI) for 67-gallium-labelled transferrin and extravascular lung water (EVLW) by transpulmonary thermal-dye dilution as measures of pulmonary permeability and oedema, respectively. ALI/ARDS was characterised by consensus criteria and the lung injury score (LIS). Plasma VEGF and von Willebrand factor (VWF) levels were assayed. <h3>Results:</h3> Angiopoietin-2, VWF, PLI, EVLW and LIS were higher in patients with sepsis than in those without sepsis and higher in patients with ALI/ARDS (n = 10/12 in sepsis, n = 19/8 in non-sepsis) than in those without. VEGF was also higher in patients with sepsis than in those without. Patients with high PLI, regardless of EVLW, had higher angiopoietin-2 levels than patients with normal PLI and EVLW. Angiopoietin-2 correlated with the PLI, LIS and VWF levels (minimum r = 0.34, p&lt;0.001) but not with EVLW. Angiopoietin-2 and VWF were predictive for ARDS in receiver operating characteristic curves (minimum area under the curve = 0.69, p = 0.006). Angiopoietin-1 and VEGF did not relate to the permeability oedema of ALI/ARDS. <h3>Conclusion:</h3> Circulating angiopoietin-2 is associated with pulmonary permeability oedema, occurrence and severity of ALI/ARDS in patients with and without sepsis. The correlation of angiopoietin-2 with VWF suggests activated endothelium as a common source.
Myocardial Infarction in Young Women in Relation to Plasma Total Homocysteine, Folate, and a Common Variant in the Methylenetetrahydrofolate Reductase Gene
Authors: Stephen M. Schwartz, David S. Siscovick, M. Rene Malinow, Frits R. Rosendaal, R. Kevin Beverly, David L. Hess, Bruce M. Psaty, W. T. Longstreth, Thomas D. Koepsell, T. E. Raghunathan, Pieter H. Reitsma
Journal: Circulation (1997)

Background In a population-based study, we examined the relationship between the risk of myocardial infarction (MI) among young women and plasma total homocysteine (tHCY), folate, vitamin B 12 , and a common cytosine (C) to thymine (T) polymorphism in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR). Methods and Results In-person interviews and nonfasting blood samples were obtained from 79 women &lt;45 years old diagnosed with MI and 386 demographically similar control subjects living in western Washington state between 1991 and 1995. Compared with control subjects, case patients had higher mean tHCY concentrations (13.4±5.2 versus 11.1±4.4 μmol/L, P =.0004) and lower mean folate concentrations (12.4±13.4 versus 16.1±12.2 nmol/L, P =.018). There was no difference in vitamin B 12 concentrations between case patients and control subjects (346.8±188.4 versus 349.7±132.4 pmol/L, P =.90). After adjusting for cardiovascular risk factors, we found that women with tHCY ≥15.6 μmol/L were at approximately twice the risk of MI as women with tHCY &lt;10.0 μmol/L (OR, 2.3; 95% CI, 0.94 to 5.64). Women with folate ≥8.39 nmol/L had an ≈50% lower risk of MI than women with folate &lt;5.27 nmol/L (OR, 0.54; 95% CI, 0.23 to 1.28). There was no association with vitamin B 12 concentration. Among control subjects, 12.7% were homozygous for the MTHFR T 677 allele, and these women had higher plasma tHCY and lower plasma folate than women with other genotypes. Ten percent of case patients were homozygous for te T 677 allele, and there was no association of homozygosity for T 677 with MI risk (OR, 0.90; 95% CI, 0.31 to 2.29). Conclusions These data support the hypothesis that elevated plasma tHCY and low plasma folate are risk factors for MI among young women. Although homozygosity for MTHFR T 677 is related to increased plasma tHCY and low plasma folate, this genetic characteristic is not a risk factor for MI in this population.
Fewer Dollars, More Sense
Authors: David H. Garfield, Aleck Hercbergs
Journal: Journal of Clinical Oncology (2008)

gliomas. 3 Notably, those patients with an early-onset and sustained elevation of thyroid-stimulating hormone (TSH)— defined as occurring within 3 months of entering the study— had a 6-month progression-free survival of 58% as compared with 0% of those who did not (P .002). In addition, the median survival for the former was 9.7 months as compared with 2.2 months for the latter (P .01). There were six magnetic resonance imaging responses in hypothyroid patients as compared with zero in the euthyroid individuals (P .02). The nadir of the free thyroxine decline also correlated positively with survival (P .003). Interestingly, only one patient developed symptomatic hypothyroidism. It has been demonstrated that the notoriously vascular GBM overexpresses—among a number of factors—vascular endothelial growth factor (VEGF), which is produced by tumor and stromal cells, including inflammatory cells. 2 VEGF then acts by paracrine mechanisms on local endothelial cells, resulting in their proliferation, survival, and migration. 4 In addition, the insulin-like growth factor-I receptor (IGF-1R) pathway is highly overexpressed in GBM. 5 The IGF-1R pathway can, in turn, induce VEGF mRNA expression via the mitogen-activated protein kinase pathway. 6 Relative to this, a GBM cell line has been shown to activate phosphophoinositol-3 kinase through IGF-1R, thereby bypassing the effects of epidermal growth factor receptor (EGFR) inhibition on phosphophoinositol-3 kinase. 7 The astrocyte (cell of origin of GBM) has been shown to be a focus of thyroid hormone (TH) action. 8 In that regard, TH has been shown to modulate expression of IGF-1R. Phosphorylation of IGF-1R by TH in 293T cell lines has been observed, whereas TH deprivation reduced proliferation in glioma cell lines. 8
Combined-Modality Therapy Versus Radiotherapy Alone for Treatment of Early-Stage Hodgkin's Disease: Cure Balanced Against Complications
Authors: Bridget F. Koontz, John P. Kirkpatrick, Robert W. Clough, Robert G. Prosnitz, Jon P. Gockerman, Joseph O. Moore, Leonard R. Prosnitz
Journal: Journal of Clinical Oncology (2006)

The treatment of early-stage Hodgkin's disease (HD) has evolved from radiotherapy alone (RT) to combined-modality therapy (CMT) because of concerns about late adverse effects from high-dose subtotal nodal irradiation (STNI). However, there is little information regarding the long-term results of CMT programs that substantially reduce the dose and extent of radiation. In addition, lowering the total radiation dose may reduce the complication rate without compromising cure. This retrospective study compares the long-term results of STNI with CMT using modestly reduced RT dose in the treatment of early-stage HD.Between 1982 and 2002, 111 patients with stage IA and IIA HD were treated definitively with RT (mean dose, 37.9 Gy); 70 patients were treated with CMT with low-dose involved-field radiotherapy (LDIFRT; mean dose, 25.5 Gy). Median follow-up was 11.7 years for RT patients and 8.1 years for the CMT group.There was a trend toward improved 20-year overall survival with CMT (83% v 70%; P = .405). No second cancers were observed in the CMT group; in the RT group the actuarial frequency of a second cancer was 16% at 20 years. There was no difference in the frequency of cardiac complications (9% v 6%, RT v CMT).In this retrospective review, CMT with LDIFRT was effective in curing early-stage HD and was not associated with an increase in second malignancies. For RT alone, a moderate dose seemed to reduce cardiac complications but did not lessen second malignancies compared with higher doses used historically.
Longitudinal pulmonary function of childhood bronchiectasis and comparison with cystic fibrosis
Authors: J Twiss, A W Stewart, C A Byrnes
Journal: Thorax (2006)

<b>Background:</b> Little has been published on the progression of non-cystic fibrosis bronchiectasis (BX), especially in childhood. Data are needed for prognosis and evaluation of the effectiveness of treatments. A study was undertaken to evaluate the change in lung function over time in children with BX, and to consider covariates and compare them with the local cystic fibrosis (CF) population. <b>Methods:</b> Children with BX or CF and ⩾3 calendar years of lung function data were identified from hospital clinics. Diagnosis was made by high resolution CT scans, sweat tests, and genetic studies. Lung function performed on a single plethysmograph between 6 and 15 years of age and ⩾6 weeks after diagnosis was analysed longitudinally (linear mixed model). The impact of reference equation and "best annual" versus "all data" approaches were evaluated. <b>Results:</b> There were 44 children in each of the BX and CF groups with an overall mean 5.7 calendar years follow up data. The estimated forced expiratory volume in 1 second (FEV<sub>1</sub>) in the BX group had an intercept of 68% predicted (Polgar) at 10 years of age which fell at a rate of 1.9% per annum using "best annual" data compared with 63% and 0.9% using "all data". Those with post-infectious BX or chronic <i>Haemophilus influenzae</i> infection had more severe disease. In CF the FEV<sub>1</sub> ("best annual") intercept was 85% predicted with a slope of −2.9% per annum. The choice of reference equation affected the magnitude of the result but not the conclusions. <b>Conclusion:</b> Children with BX have significant airway obstruction which deteriorates over time, regardless of analysis strategy or reference. Effective interventions are needed to prevent significant morbidity and adult mortality.
Effects of Neomycin Alone and in Combination with Cholestyramine on Serum Cholesterol and Fecal Steroids in Hypercholesterolemic Subjects
Authors: Tatu A. Miettinen
Journal: Journal of Clinical Investigation (1979)

Effects of neomycin were studied on serum cholesterol and fecal steroids in hypercholesterolemic patients during a short treatment period (4 wk) and a long treatment period (16 mo), using small (1.5 g/d) and large (up to 6 g/d) doses alone and in combination with cholestyramine. In the short-term low-dose study the decrease in serum cholesterol by 21% was associated with a proportionate increase in fecal cholesterol elimination as neutral sterols through impaired cholesterol absorption. Serum cholesterol remained low and fecal steroid excretion remained elevated in the long-term neomycin study. Increasing the dosage from 1.5 to 6 g/d at the end of the 16-mo period brought about a further slight decrease in serum cholesterol and a small further increase in fecal neutral and acidic steroids. The increases in fecal bile acids and fat but not in neutral sterols were positively correlated with the increases in the neomycin dosage. Thus, large neomycin doses can also cause bile acid malabsorption. In another series of patients, a decrease (25%) in serum cholesterol by cholestyramine was associated with a proportional increase in the fecal elimination of cholesterol (2.5-fold) as bile acids. The inclusion of neomycin in cholestyramine therapy further increased fecal steroid output (solely as neutral sterols) by only about one-fifth of that due to cholestyramine, but further decreased serum cholesterol almost to the same extent (-17%) as cholestyramine alone. The overall decrease was 38%, no side effects occurred, and the patients found combination therapy convenient. Neomycin decreased serum cholesterol in different studies by 10±2, 17±4, and 12±4% per 100 mg/d of the increment in fecal steroids, the respective decrease for cholestyramine being only 2.2±0.5%. Thus, neomycin effectively reduced serum cholesterol by a relatively small increase in cholesterol elimination (via cholesterol malabsorption) compared with cholestyramine-induced bile acid malabsorption.
Cdc42 Regulates Adherens Junction Stability and Endothelial Permeability by Inducing α-Catenin Interaction With the Vascular Endothelial Cadherin Complex
Authors: Michael T. Broman, Panos Kouklis, Xiaopei Gao, Ramaswamy Ramchandran, Radu F. Neamu, Richard D. Minshall, Asrar B. Malik
Journal: Circulation Research (2005)

The endothelial adherens junctions (AJs) consist of trans-oligomers of membrane spanning vascular endothelial (VE)-cadherin proteins, which bind beta-catenin through their cytoplasmic domain. beta-Catenin in turn binds alpha-catenin and connects the AJ complex with the actin cytoskeleton. We addressed the in vivo effects of loss of VE-cadherin interactions on lung vascular endothelial permeability and the role of specific Rho GTPase effectors in regulating the increase in permeability induced by AJ destabilization. We used cationic liposomes encapsulating the mutant of VE-cadherin lacking the extracellular domain (DeltaEXD) to interfere with AJ assembly in mouse lung endothelial cells. We observed that lung vascular permeability (quantified as microvessel filtration coefficient [K(f,c)]) was increased 5-fold in lungs expressing DeltaEXD. This did not occur to the same degree on expression of the VE-cadherin mutant, DeltaEXDDeltabeta, lacking the beta-catenin-binding site. The increased vascular permeability was the result of destabilization of VE-cadherin homotypic interaction induced by a shift in the binding of beta-catenin from wild-type VE-cadherin to the expressed DeltaEXD mutant. Because DeltaEXD expression in endothelial cells activated the Rho GTPase Cdc42, we addressed its role in the mechanism of increased endothelial permeability induced by AJ destabilization. Coexpression of dominant-negative Cdc42 (N17Cdc42) prevented the increase in K(f,c) induced by DeltaEXD. This was attributed to inhibition of the association of alpha-catenin with the DeltaEXD-beta-catenin complex. The results demonstrate that Cdc42 regulates AJ permeability by controlling the binding of alpha-catenin with beta-catenin and the consequent interaction of the VE-cadherin/catenin complex with the actin cytoskeleton.
Selection Is No More Efficient in Haploid than in Diploid Life Stages of an Angiosperm and a Moss
Authors: Péter Szövényi, Mariana Ricca, Zsófia Hock, Jonathan A. Shaw, Kentaro K. Shimizu, Andreas Wagner
Journal: Molecular Biology and Evolution (2013)

The masking hypothesis predicts that selection is more efficient in haploids than in diploids, because dominant alleles can mask the deleterious effects of recessive alleles in diploids. However, gene expression breadth and noise can potentially counteract the effect of masking on the rate at which genes evolve. Land plants are ideal to ask whether masking, expression breadth, or expression noise dominate in their influence on the rate of molecular evolution, because they have a biphasic life cycle in which the duration and complexity of the haploid and diploid phase varies among organisms. Here, we generate and compile genome-wide gene expression, sequence divergence, and polymorphism data for Arabidopsis thaliana and for the moss Funaria hygrometrica to show that the evolutionary rates of haploid- and diploid-specific genes contradict the masking hypothesis. Haploid-specific genes do not evolve more slowly than diploid-specific genes in either organism. Our data suggest that gene expression breadth influence the evolutionary rate of phase-specific genes more strongly than masking. Our observations have implications for the role of haploid life stages in the purging of deleterious mutations, as well as for the evolution of ploidy.