tbuckley/cabot-search huggingface dataset:
Computer modelling and visualisation of the microscopic distributions of hyperpolarised gas diffusivity in models of acinar airways
Authors: Juan Parra-Robles, Xiaojun Xu, Jim M. Wild
Journal: European Respiratory Journal (2011)

Diffusion MRI using hyperpolarized gases is sensitive to lung microstructure. Computer simulations used to investigate the relationship between diffusivity (ADC) and airway dimensions are generally limited by non-realistic geometric assumptions (e.g. infinite cylindrical airways). In this work, we use histology sections to generate realistic models of acinar airways that are used in finite element computer simulations of 3He and 129Xe gas diffusion and 129Xe exchange between gas and tissue.  Results:  For 3He, the distribution over the largest airway is nearly uniform due to motional averaging. For 129Xe, its reduced diffusivity limits the mixing between intra and extra-alveolar gas resulting in a non-uniform distribution, which can be described with a two-compartment analytical model.  These results suggest that 129Xe MRI may be more sensitive to alveolar structure than 3He, while being less sensitive to branching and localized diffusion effects.  Conclusion: Computer simulation and visualization of maps of microscopic diffusivity distributions in realistic acinar geometries have helped provide a better understanding of the length scales and diffusion regimes relevant to hyperpolarized gas lung MRI and may help simplify the development of 129Xe-based MR lung morphometry techniques.
Aspirin and alcohol in gastrointestinal haemorrhage
Authors: C. D. Needham, J. Kyle, P. F. Jones, S. J. Johnston, D. F. Kerridge
Journal: Gut (1971)

The intake of aspirin, of alcohol, and of a combination of both, among 817 patients admitted for gastrointestinal haemorrhage is reported. The incidence of ingestion in six diagnostic groups is compared with that in two control groups. Analysis confirms that there is a markedly significant association between overt haemorrhage and the ingestion of aspirin, but this was not shown for alcohol taken alone: the combination of aspirin and alcohol showed a highly significant synergistic effect.
Combined PI3K/mTOR and MEK Inhibition Provides Broad Antitumor Activity in Faithful Murine Cancer Models
Authors: Patrick J. Roberts, Jerry E. Usary, David B. Darr, Patrick M. Dillon, Adam D. Pfefferle, Martin C. Whittle, James S. Duncan, Soren M. Johnson, Austin J. Combest, Jian Jin, William C. Zamboni, Gary L. Johnson, Charles M. Perou, Norman E. Sharpless
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Anticancer drug development is inefficient, but genetically engineered murine models (GEMM) and orthotopic, syngeneic transplants (OST) of cancer may offer advantages to in vitro and xenograft systems. Experimental Design: We assessed the activity of 16 treatment regimens in a RAS-driven, Ink4a/Arf-deficient melanoma GEMM. In addition, we tested a subset of treatment regimens in three breast cancer models representing distinct breast cancer subtypes: claudin-low (T11 OST), basal-like (C3-TAg GEMM), and luminal B (MMTV-Neu GEMM). Results: Like human RAS-mutant melanoma, the melanoma GEMM was refractory to chemotherapy and single-agent small molecule therapies. Combined treatment with AZD6244 [mitogen-activated protein–extracellular signal-regulated kinase kinase (MEK) inhibitor] and BEZ235 [dual phosphoinositide-3 kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor] was the only treatment regimen to exhibit significant antitumor activity, showed by marked tumor regression and improved survival. Given the surprising activity of the “AZD/BEZ” combination in the melanoma GEMM, we next tested this regimen in the “claudin-low” breast cancer model that shares gene expression features with melanoma. The AZD/BEZ regimen also exhibited significant activity in this model, leading us to testing in even more diverse GEMMs of basal-like and luminal breast cancer. The AZD/BEZ combination was highly active in these distinct breast cancer models, showing equal or greater efficacy compared with any other regimen tested in studies of over 700 tumor-bearing mice. This regimen even exhibited activity in lapatinib-resistant HER2+ tumors. Conclusion: These results show the use of credentialed murine models for large-scale efficacy testing of diverse anticancer regimens and predict that combinations of PI3K/mTOR and MEK inhibitors will show antitumor activity in a wide range of human malignancies. Clin Cancer Res; 18(19); 5290–303. ©2012 AACR.
Stromal Myofibroblasts Predict Disease Recurrence for Colorectal Cancer
Authors: Tadashi Tsujino, Iwao Seshimo, Hirofumi Yamamoto, Chew Yee Ngan, Koji Ezumi, Ichiro Takemasa, Masataka Ikeda, Mitsugu Sekimoto, Nariaki Matsuura, Morito Monden
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Myofibroblasts, which are specifically differentiated fibroblasts, are thought to play a central role in the desmoplastic reaction, a dynamic stromal change closely associated with cancer development. Although fundamental studies suggest that myofibroblasts may either facilitate or inhibit cancer progression, cumulative evidence supports their role in promoting tumor progression. The aim of this study was to assess the value of myofibroblasts in the cancer stroma as an indicator of disease recurrence after colorectal cancer surgery. Experimental Design: Using computer-assisted image analysis, we quantified myofibroblasts in the cancer-associated stroma of 192 colorectal cancers using α-smooth muscle actin as a marker. Results: The cancer-associated stroma contained various numbers of myofibroblasts (0.35-19.0%; mean, 5.55 ± 3.85%). Tumors with abundant myofibroblasts were associated with shorter disease-free survival rate (P = 0.001) for stage II and III colorectal cancer. Multivariate analysis indicated that α-smooth muscle actin was a significant prognostic factor comparable with lymph node metastasis and superior to other tumor and stromal components, including histology of the tumor invasive front, peritumoral lymphocytic infiltration, and Crohn's-like lymphoid reaction. Moreover, colorectal cancers with synchronous liver metastasis generally displayed an active desmoplastic reaction, which was retained in the metastatic lesion to a similar extent. Conclusions: The results suggest that the abundance of myofibroblasts in cancer-associated stroma may be a useful indicator of disease recurrence after curative colorectal cancer surgery.
Fulminant hepatitis associated with hepatitis B virus e antigen–negative infection: Importance of host factors
Authors: Peter Karayiannis, Alexandra Alexopoulou, Stephanos Hadziyannis, Mark Thursz, Richard Watts, Seiji Seito, Howard C. Thomas
Journal: Hepatology (1995)

The precore stop-codon variant of hepatitis B virus (HBV) has been implicated in fulminant hepatitis. The precore/core regions of such variants from two sets of patients with interpartner transmission resulting in fulminant hepatitis in the contact, were sequenced to establish whether further sequence variations in the core region are specifically associated with the fulminant disease. In both sets of patients, there was sequence diversity of the precore/core region from the wild type, leading to numerous amino acid substitutions in the core region. Between the infecting source and the contact, there was only one amino acid change in one set of patients and none in the other. In addition, in the second set of patients, serum samples from four different time points were investigated. Sequence data showed no variation in each patient at the nucleotide level in the core region, even in the case of the source, who was followed for 3 years. In this same pair of subjects, the remainder of the genome was sequenced and was identical at the nucleotide level. Therefore, it appears that, at least in some cases of fulminant hepatitis caused by infection with the precore variant, the nucleotide sequence of the patient with fulminant hepatitis is identical to that observed in the asymptomatic source of infection. These data indicate that the severity and outcome of infection in such cases are unrelated to any additional variation in the entire HBV genome, and that the changed clinical picture is dependent on host factors, possibly the HLA environment. HLA typing of both the contact and source in the two sets of patients revealed that the contacts with fulminant hepatitis had one or more alleles at the HLA class II locus, previously shown to be associated with an acute hepatitis sufficient to clear the virus. (Hepatology 1995; 22:1628-1634).
Structured Personal Diabetes Care in Primary Health Care Affects Only Women’s HbA1c
Authors: Anni B.S. Nielsen, Niels de Fine Olivarius, Dorte Gannik, Charlotte Hindsberger, Hanne Hollnagel
Journal: Diabetes Care (2006)

OBJECTIVE—Diabetic men and women differ in lifestyle and attitudes toward diabetes and may benefit differently from interventions to improve glycemic control. We explored the relation between HbA1c (A1C), sex, treatment allocation, and their interactions with behavioral and attitudinal characteristics in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Six years after their diabetes diagnosis, a population-based sample of 874 primary care patients cluster-randomized to receive structured personal care or routine care reported lifestyle, medication, social support, diabetes-related consultations, and attitudes toward diabetes. Multivariate analyses were applied, split by sex. RESULTS—A marked intervention effect on A1C was confined to the structured personal care women. The median A1C was 8.4% in structured personal care women and 9.2% in routine care women (P &amp;lt; 0.0001) and 8.5% in structured personal care men and 8.9% in routine care men (P = 0.052). Routine care women had a 1.10 times higher A1C than structured personal care women, (P &amp;lt; 0.0001, adjusted analysis). Structured personal care women had relatively more consultations than routine care women, but neither number of consultations nor other covariates helped to explain the sex difference in A1C. Irrespective of treatment allocation, women had more adaptive attitudes toward diabetes but lacked support compared with men. CONCLUSIONS—In this study, the observed effect of structured personal care on A1C was present only among women, possibly because they were more inclined to comply with regular follow-up and had a tendency to have a more adaptive attitude toward diabetes.
Adenosine and arteriogenesis: promoter or suppressor?
Authors: Masatoshi Fujita
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Lack of ecto-5′-nucleotidase (CD73) promotes arteriogenesis’ by Y.C. Boring et al ., pp. 88-96, this issue. 

The principal therapeutic approach to atherosclerotic obstructive disease is to provide a sufficient blood flow to the jeopardized area perfused by the severely narrowed or occluded artery, which is accomplished by bypass grafting surgery, percutaneous transluminal intervention, and angiogenic therapy. Angiogenesis has been clearly separated into arteriogenesis and angiogenesis in a narrow sense in a rabbit hindlimb ischaemia model.1 Using the experimental model, Schaper et al. 2 established a conceptual framework of arteriogenesis.2 A pressure gradient across the collateral network increases the collateral blood flow, with resultant augmented fluid shear stress at the site of collateral vessels. Vascular endothelium activated by increased shear stress produces and releases monocyte chemotactic protein-1 (MCP-1) and adhesion molecules.3 Accumulated monocytes produce various angiogenic growth factors …
Disposal of Human Chylomicrons Administered Intravenously in Ischemic Heart Disease and Essential Hyperlipemia
Authors: P. J. Nestel, M. A. Denborough, J. O'Dea
Journal: Circulation Research (1962)

Human lymph chylomicrons labeled in vivo with C-14 palmitate were infused into eight patients with ischemic heart disease and into eight control subjects. The mean rates of removal of radioactivity from the chylomicron fraction of the plasmas of these subjects were found to be the same in the two groups. Labeled chylomicrons were also prepared from the blood of six patients with ischemic heart disease and of six controls, and infused into six recipients as paired infusions. Radioactivity from chylomicrons obtained from patients with ischemic heart disease was as readily removed from the circulations of recipients as was radioactivity from chylomicrons obtained from control subjects. When lymph chylomicrons were infused into two patients with hyperlipemia, the rate of removal of chylomicron radioactivity was considerably less than normal and appeared to be related to the levels of endogenous esterified fatty acids.
Properties of Hyperthyroid Rat Myocardium
Authors: W. V. WHITEHORN, W. C. ULLRICK, B. R. ANDERSEN
Journal: Circulation Research (1959)

Electric and mechanical properties of right and left ventricular muscle of hyperthyroid rats have been studied in vitro. Excitability was not modified but refractory period was lengthened in left ventricular muscle. Developed tension was significantly reduced in both ventricles, the greater reduction being on the right. The results suggest direct and disproportionate effects of thyroid hormone on right and left ventricular myocardium.
Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes
Authors: Ralph A. DeFronzo, Devjit Tripathy
Journal: Diabetes Care (2009)

Insulin resistance is a characteristic feature of type 2 diabetes and plays a major role in the pathogenesis of the disease (1,2). Although β-cell failure is the sine qua non for development of type 2 diabetes, skeletal muscle insulin resistance is considered to be the initiating or primary defect that is evident decades before β-cell failure and overt hyperglycemia develops (3,4). Insulin resistance is defined as a reduced response of target tissues (compared with subjects with normal glucose tolerance [NGT] without a family history of diabetes), such as the skeletal muscle, liver, and adipocytes, to insulin. Because skeletal muscle is the predominant site of insulin-mediated glucose uptake in the postprandial state, here we will focus on recent advances about the time of onset, as well as the mechanism, of the skeletal muscle insulin resistance.

The euglycemic insulin clamp technique (5) is considered to be the gold standard for measuring insulin action in vivo. With this technique, whole-body insulin action is quantified as the rate of exogenous glucose infusion (plus any residual hepatic glucose production) required to maintain the plasma glucose concentration at euglycemic levels in response to a fixed increment in the plasma insulin concentration. Because 80–90% of the infused glucose is taken up by skeletal muscle under conditions of euglycemic hyperinsulinemia, insulin sensitivity measured with the insulin clamp technique primarily reflects skeletal muscle (6). Another advantage of this technique is that it can be combined with indirect calorimetry to measure different substrate oxidation rates and with muscle biopsy to examine the biochemical/molecular etiology of the insulin resistance. Measurement of insulin sensitivity by the frequently sampled intravenous glucose tolerance test reflects both hepatic and peripheral insulin resistance and correlates well with the insulin clamp technique (7).

Because insulin clamp studies are not feasible in large …
Prognostic Indicators and Survival in Patients With Stage IIIB Inflammatory Breast Carcinoma After Dose-Intense Chemotherapy
Authors: George Somlo, Paul Frankel, Warren Chow, Lucille Leong, Kim Margolin, Robert Morgan, Stephen Shibata, Peiguo Chu, Stephen Forman, Dean Lim, Przemyslaw Twardowski, Jeffrey Weitzel, Joseph Alvarnas, Neil Kogut, Jeffrey Schriber, Eleanor Fermin, Yun Yen, Lloyd Damon, James H. Doroshow
Journal: Journal of Clinical Oncology (2004)

Purpose To improve treatment outcome for patients presenting with inflammatory breast cancer (IBC), we have sequentially developed and tested single and tandem dose-intense chemotherapy regimens (DICT). Tumor- and treatment-related factors were analyzed to generate a prognostic model. Patients and Methods Between May 1989 and April 2002, 120 patients received conventional-dose chemotherapy, surgery, and sequentially developed single- or tandem-cycle DICT. Disease- and treatment-specific features were subjected to univariate and multivariate analysis to correlate with outcome. Results At a median follow-up of 61 months (range, 21 to 161 months), estimated 5-year relapse-free survival (RFS) and overall survival (OS) were 44% (95% CI, 34% to 53%) and 64% (95% CI, 55% to 73%), respectively. In an age-adjusted multivariate analysis, RFS was better in patients with estrogen receptor (ER)/progesterone receptor (PR)–positive tumors (P = .002), for patients with fewer than four involved axillary nodes before DICT (P = .01), and in patients treated with radiation therapy (P = .001) and tandem DICT (P = .049). OS was improved in patients with ER/PR-positive tumors (P = .002), in those with fewer than four involved axillary nodes before DICT (P = .03), and in patients treated with radiation therapy (P = .002). Conclusion This retrospective analysis suggests that either single or tandem DICT can be administered safely and may benefit selected patients with stage IIIB IBC. Those with receptor-negative IBC and with four or more involved axillary nodes before DICT need improved neoadjuvant and postadjuvant intensification therapy. A prospective randomized trial of single versus tandem DICT would be required to confirm the potential benefit of tandem DICT in the setting of IBC.
A new method of measuring propagation coefficients and characteristic impedance in blood vessels.
Authors: W R Milnor, W W Nichols
Journal: Circulation Research (1975)

True propagation coefficients of pulse wave harmonics in an artery can be determined in vivo by measuring pulsatile blood pressure and flow at each of two points along the length of the vessel. These coefficients, which are complex numbers that describe the attenuation and the phase shift imposed on a traveling wave, are independent of the reflected waves in the circulation and thus provide information about the viscoelastic state and other properties of an artery. The equations involved are implicit in standard transmission-line theory, but they have not previously been applied in this particular way to blood vessels. The femoral artery, exposed in situ, was studied in 11 anesthetized dogs. At 1.5 Hz, true attenuation constants averaged 0.0151 nepers/cm, and true phase constants averaged 0.0155 radians/cm. As frequency increased, the apparent phase velocity of flow, in contrast, was relatively low at the first harmonic and rose as frequency increased. True phase velocities lay between the apparent pressure and flow values. Characteristic impedance at 1.5 Hz had an average modulus of 1.76 times 10-4 dyne sec/cm5 and a phase of minus 0.31 radians. The modulus diminished as frequency increased, and the phase became less negative. These results show that true phase constants and characteristic impedances determined by this method are consistent with data reported by others and provide information not previously available about flow wave propagation.
Tracing the Evolution of the Floral Homeotic B- and C-Function Genes through Genome Synteny
Authors: B. Causier, R. Castillo, Y. Xue, Z. Schwarz-Sommer, B. Davies
Journal: Molecular Biology and Evolution (2010)

The evolution of the floral homeotic genes has been characterized using phylogenetic and functional studies. It is possible to enhance these studies by comparing gene content and order between species to determine the evolutionary history of the regulatory genes. Here, we use a synteny-based approach to trace the evolution of the floral B- and C-function genes that are required for specification of the reproductive organs. Consistent with previous phylogenetic studies, we show that the euAP3-TM6 split occurred after the monocots and dicots diverged. The Arabidopsis TM6 and papaya euAP3 genes are absent from the respective genomes, and we have detected loci from which these genes were lost. These data indicate that either the TM6 or the euAP3 lineage genes can be lost without detriment to flower development. In contrast, PI is essential for male reproductive organ development; yet, contrary to predictions, complex genomic rearrangements have resulted in almost complete breakdown of synteny at the PI locus. In addition to showing the evolution of B-function genes through the prediction of ancestral loci, similar reconstructions reveal the origins of the C-function AG and PLE lineages in dicots, and show the shared ancestry with the monocot C-function genes. During our studies, we found that transposable elements (TEs) present in sequenced Antirrhinum genomic clones limited comparative studies. A pilot survey of the Antirrhinum data revealed that gene-rich regions contain an unusually high degree of TEs of very varied types, which will be an important consideration for future genome sequencing efforts.
Does Childhood Cancer Affect Parental Divorce Rates? A Population-Based Study
Authors: Astri Syse, Jon H. Loge, Torkild H. Lyngstad
Journal: Journal of Clinical Oncology (2009)

PURPOSE Cancer in children may profoundly affect parents' personal relationships in terms of psychological stress and an increased care burden. This could hypothetically elevate divorce rates. Few studies on divorce occurrence exist, so the effect of childhood cancers on parental divorce rates was explored. PATIENTS AND METHODS Data on the entire Norwegian married population, age 17 to 69 years, with children age 0 to 20 years in 1974 to 2001 (N = 977,928 couples) were retrieved from the Cancer Registry, the Central Population Register, the Directorate of Taxes, and population censuses. Divorce rates for 4,590 couples who were parenting a child with cancer were compared with those of otherwise similar couples by discrete-time hazard regression models. Results Cancer in a child was not associated with an increased risk of parental divorce overall. An increased divorce rate was observed with Wilms tumor (odds ratio [OR], 1.52) but not with any of the other common childhood cancers. The child's age at diagnosis, time elapsed from diagnosis, and death from cancer did not influence divorce rates significantly. Increased divorce rates were observed for couples in whom the mothers had an education greater than high school level (OR, 1.16); the risk was particularly high shortly after diagnosis, for CNS cancers and Wilms tumors, for couples with children 0 to 9 years of age at diagnosis, and after a child's death. CONCLUSION This large, registry-based study shows that cancer in children is not associated with an increased parental divorce rate, except with Wilms tumors. Couples in whom the wife is highly educated appear to face increased divorce rates after a child's cancer, and this may warrant additional study.