tbuckley/cabot-search huggingface dataset:
Neighbor-Net: An Agglomerative Method for the Construction of Phylogenetic Networks
Authors: D. Bryant
Journal: Molecular Biology and Evolution (2003)

We present Neighbor-Net, a distance based method for constructing phylogenetic networks that is based on the Neighbor-Joining (NJ) algorithm of Saitou and Nei. Neighbor-Net provides a snapshot of the data that can guide more detailed analysis. Unlike split decomposition, Neighbor-Net scales well and can quickly produce detailed and informative networks for several hundred taxa. We illustrate the method by reanalyzing three published data sets: a collection of 110 highly recombinant Salmonella multi-locus sequence typing sequences, the 135 “African Eve” human mitochondrial sequences published by Vigilant et al., and a collection of 12 Archeal chaperonin sequences demonstrating strong evidence for gene conversion. Neighbor-Net is available as part of the SplitsTree4 software package.
Polyclonal nature of diffuse proliferation of interstitial cells of Cajal in patients with familial and multiple gastrointestinal stromal tumours
Authors: H Chen
Journal: Gut (2002)

<b>Background:</b> Diffuse proliferation of interstitial cells of Cajal (ICCs) in the myenteric plexus layer of the intestine has been described in patients with familial and multiple gastrointestinal stromal tumours (GISTs). However, it is not fully understood whether proliferation is polyclonal or monoclonal. <b>Aims:</b> To evaluate the clonal nature of diffuse ICC proliferation in familial and multiple GIST cases, we carried out clonal analysis using inactivation at the human androgen receptor (HUMARA) locus. <b>Materials and methods:</b> Diffuse ICC proliferation tissues from three female patients were microdissected using a laser capture microdissection (LCM) system. Normal intestinal mucosal tissues were also microdissected for polyclonal controls and GIST tissues for monoclonal controls from the same patients, and genomic DNA was extracted. After digestion by restriction enzyme HhaI, the HUMARA locus was amplified by a fluorescent polymerase chain reaction (PCR) procedure and the PCR products were analysed. <b>Results:</b> One case was uninformative because it was homozygous at the HUMARA locus. In the two other cases, PCR products from the diffuse ICC proliferation showed two alleles as well as those from normal intestinal mucosal tissues, indicating that ICC proliferation was polyclonal. In contrast, PCR products from associated GIST tissues showed only one allele, indicating that GISTs were monoclonal. <b>Conclusion:</b> The results suggested that diffuse ICC proliferation in familial and multiple GIST cases was non-neoplastic hyperplasia.
Inhibitory Effects of Sendai Virus on Friend Virus Leukemia in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E. Frederick Wheelock, M.D., Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1967)

Sendai virus (SV) inoculated before Friend virus (FV) inhibited FV replication in spleens as well as the splenomegalic and leukocytotic responses to FV infection. The response curves in mice of interferon production and of FV leukemia inhibition to increasing doses of SV were similar. Optimal interferon production and FV leukemia inhibition occurred in response to a dose of SV less than the maximum dose tested. SV markedly protected significant numbers of mice from leukemia when it was inoculated as early as 6 weeks before FV. No protection occurred, however, when the interval between virus inoculations was extended to 9 weeks. At least 10% of mice inoculated with SV 3 weeks prior to FV exhibited no signs of leukemia 6 months after all FV control mice had died.
Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency.
Authors: J C Brackett, H F Sims, P Rinaldo, S Shapiro, C K Powell, M J Bennett, A W Strauss
Journal: Journal of Clinical Investigation (1995)

Human trifunctional protein catalyzes three steps in mitochondrial beta-oxidation of fatty acids, including the long chain 3-hydroxyacyl-CoA dehydrogenase step. Deficiency of this heterocomplex, which contains 4 alpha and 4 beta subunits, causes sudden unexplained infant death, a Reye-like syndrome, cardiomyopathy, or skeletal myopathy. We determined the molecular basis of this deficiency in a patient with neonatal presentation and later sudden death using reverse transcription and PCR amplification of his alpha subunit mRNA. We demonstrated a universal deletion of exon 3 (71 bp) in his mRNA. This deletion causes a frameshift and very early premature termination. Amplification of genomic DNA demonstrated that the patient was a compound heterozygote with two different mutations in the 5' donor splice site following exon 3: a paternally inherited G to A transversion at the invariant position +1 and a maternally inherited A to G mutation at position +3. Both allelic mutations apparently cause exon 3 skipping, resulting in undetectable levels of alpha subunit protein, and complete loss of trifunctional protein. This is the initial molecular characterization of trifunctional protein deficiency.
A <i>Drosophila melanogaster</i> Model of Diastolic Dysfunction and Cardiomyopathy Based on Impaired Troponin-T Function
Authors: Meera Cozhimuttam Viswanathan, Gaurav Kaushik, Adam J. Engler, William Lehman, Anthony Cammarato
Journal: Circulation Research (2013)

Regulation of striated muscle contraction is achieved by Ca2+ -dependent steric modulation of myosin cross-bridge cycling on actin by the thin filament troponin-tropomyosin complex. Alterations in the complex can induce contractile dysregulation and disease. For example, mutations between or near residues 112 to 136 of cardiac troponin-T, the crucial TnT1 (N-terminal domain of troponin-T)-tropomyosin-binding region, cause cardiomyopathy. The Drosophila upheld(101) Glu/Lys amino acid substitution lies C-terminally adjacent to this phylogenetically conserved sequence.Using a highly integrative approach, we sought to determine the molecular trigger of upheld(101) myofibrillar degeneration, to evaluate contractile performance in the mutant cardiomyocytes, and to examine the effects of the mutation on the entire Drosophila heart to elucidate regulatory roles for conserved TnT1 regions and provide possible mechanistic insight into cardiac dysfunction.Live video imaging of Drosophila cardiac tubes revealed that the troponin-T mutation prolongs systole and restricts diastolic dimensions of the heart, because of increased numbers of actively cycling myosin cross-bridges. Elevated resting myocardial stiffness, consistent with upheld(101) diastolic dysfunction, was confirmed by an atomic force microscopy-based nanoindentation approach. Direct visualization of mutant thin filaments via electron microscopy and 3-dimensional reconstruction resolved destabilized tropomyosin positioning and aberrantly exposed myosin-binding sites under low Ca2+ conditions.As a result of troponin-tropomyosin dysinhibition, upheld(101) hearts exhibited cardiac dysfunction and remodeling comparable to that observed during human restrictive cardiomyopathy. Thus, reversal of charged residues about the conserved tropomyosin-binding region of TnT1 may perturb critical intermolecular associations required for proper steric regulation, which likely elicits myopathy in our Drosophila model.
Alterations in Resting Length-Tension Relations of Cardiac Muscle Induced by Changes In Contractile Force
Authors: EDMUND H. SONNENBLICK, JOHN ROSS, JAMES W. COVELL, EUGENE BRAUNWALD
Journal: Circulation Research (1966)

Effects of sustained postextrasystolic potentiation (P.S.), norepinephrine (NE), and calcium on resting length-tension relations of heart muscle were studied in the cat papillary muscle and isovolumic dog ventricle. In papillary muscles, P.S., calcium or NE produced no change in diastolic compliance when the muscles were freely isotonic, or afterloaded, and force remained constant. However, under isometric conditions, P.S. induced a small fall in diastolic tension while systolic force rose. Similar decrements in diastolic tension were observed when force of contraction was augmented by simply increasing afterload from a constant initial muscle length. In the isovolumic ventricle, P.S., NE, and calcium each induced substantial increments in developed pressure, accompanied by small decreases in end-diastolic pressure. The latter was reduced or abolished by augmenting the initial contractile state with calcium or NE, so that the super-imposition of P.S. induced only trivial increments in developed pressure. It is concluded that P.S., calcium, or NE do not induce changes in the resting length-tension relations of heart muscle per se. However, resting length at any given resting tension does increase slightly upon the augmentation of systolic force alone. It is postulated that these findings may be explained by the existence of a series viscous component.
HEREDITARY ECTODERMAL DYSPLASIA.
Authors: AMARJIT SINGH, S. S. JOLLY, SURRTKBER KAUR
Journal: British Journal of Dermatology (1962)

Journal Article HEREDITARY ECTODERMAL DYSPLASIA. Get access AMARJIT SINGH, M.D., M.R.C.P., AMARJIT SINGH, M.D., M.R.C.P. Department of Medicine, Medical College, Patiala, India Search for other works by this author on: Oxford Academic Google Scholar S. S. JOLLY, M.D., S. S. JOLLY, M.D. Department of Medicine, Medical College, Patiala, India Search for other works by this author on: Oxford Academic Google Scholar SURRTKBER KAUR, M.B. SURRTKBER KAUR, M.B. Department of Medicine, Medical College, Patiala, India Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 74, Issue 1, 1 January 1962, Pages 34–37, https://doi.org/10.1111/j.1365-2133.1962.tb13909.x Published: 01 January 1962
Brain ouabain and central effects of dietary sodium in spontaneously hypertensive rats.
Authors: B S Huang, F H Leenen
Journal: Circulation Research (1992)

High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to intracerebroventricular ouabain and to mental stress and intracerebroventricular alpha 2-adrenoceptor agonist guanabenz alone or preceded by intracerebroventricular ouabain were recorded in conscious SHR and Wistar-Kyoto (WKY) rats maintained from 4 to 8 weeks of age on different sodium diets: 1) low sodium intake (LNa, 17 mumol), 2) normal sodium intake (NNa, 101 mumol), and 3) HNa (1,370 mumol). SHR on NNa showed significantly higher MAP and RSNA compared with WKY rats on NNa. HNa or LNa significantly increased or decreased MAP but had no effects on resting RSNA in SHR and had no effects on resting MAP and RSNA in WKY rats. Intracerebroventricular ouabain induced dose-dependent increases in MAP, RSNA, and HR. In both SHR and WKY rats, LNa significantly enhanced these responses. In contrast, HNa significantly attenuated these responses only in SHR. Air stress increased and intracerebroventricular guanabenz decreased MAP, HR, and RSNA. The magnitudes of increases and decreases were significantly larger in SHR than in WKY rats. In WKY rats, dietary sodium did not change these responses. In contrast, in SHR, HNa significantly enhanced MAP, HR, and RSNA responses to air stress or intracerebroventricular guanabenz.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of 8 vs 15 Days of Antibiotic Therapy for Ventilator-Associated Pneumonia in Adults
Authors: Jean Chastre, Michel Wolff, Jean-Yves Fagon, Sylvie Chevret, Franck Thomas, Delphine Wermert, Eva Clementi, Jesus Gonzalez, Dominique Jusserand, Pierre Asfar, Dominique Perrin, Fabienne Fieux, Sylvie Aubas, None for the PneumA Trial Group
Journal: JAMA (2003)

The optimal duration of antimicrobial treatment for ventilator-associated pneumonia (VAP) is unknown. Shortening the length of treatment may help to contain the emergence of multiresistant bacteria in the intensive care unit (ICU).To determine whether 8 days is as effective as 15 days of antibiotic treatment of patients with microbiologically proven VAP.Prospective, randomized, double-blind (until day 8) clinical trial conducted in 51 French ICUs. A total of 401 patients diagnosed as having developed VAP by quantitative culture results of bronchoscopic specimens and who had received initial appropriate empirical antimicrobial therapy were enrolled between May 1999 and June 2002.A total of 197 patients were randomly assigned to receive 8 days and 204 to receive 15 days of therapy with an antibiotic regimen selected by the treating physician.Primary outcome measures-death from any cause, microbiologically documented pulmonary infection recurrence, and antibiotic-free days-were assessed 28 days after VAP onset and analyzed on an intent-to-treat basis.Compared with patients treated for 15 days, those treated for 8 days had neither excess mortality (18.8% vs 17.2%; difference, 1.6%; 90% confidence interval [CI], -3.7% to 6.9%) nor more recurrent infections (28.9% vs 26.0%; difference, 2.9%; 90% CI, -3.2% to 9.1%), but they had more mean (SD) antibiotic-free days (13.1 [7.4] vs 8.7 [5.2] days, P<.001). The number of mechanical ventilation-free days, the number of organ failure-free days, the length of ICU stay, and mortality rates on day 60 for the 2 groups did not differ. Although patients with VAP caused by nonfermenting gram-negative bacilli, including Pseudomonas aeruginosa, did not have more unfavorable outcomes when antimicrobial therapy lasted only 8 days, they did have a higher pulmonary infection-recurrence rate compared with those receiving 15 days of treatment (40.6% vs 25.4%; difference, 15.2%, 90% CI, 3.9%-26.6%). Among patients who developed recurrent infections, multiresistant pathogens emerged less frequently in those who had received 8 days of antibiotics (42.1% vs 62.0% of pulmonary recurrences, P =.04).Among patients who had received appropriate initial empirical therapy, with the possible exception of those developing nonfermenting gram-negative bacillus infections, comparable clinical effectiveness against VAP was obtained with the 8- and 15-day treatment regimens. The 8-day group had less antibiotic use.
Instability of BCR-ABL Gene in Primary and Cultured Chronic Myeloid Leukemia Stem Cells
Authors: X. Jiang, K. M. Saw, A. Eaves, C. Eaves
Journal: JNCI Journal of the National Cancer Institute (2007)

Imatinib mesylate treatment causes remissions in a majority of patients with chronic myeloid leukemia (CML), but relapses are an increasing problem. We hypothesized that imatinib-resistant leukemic cells emerge from CML stem cells that acquire BCR–ABL gene mutations even before exposure to BCR–ABL–targeted agents such as imatinib. Lineage-negative (i.e., immature) CD34 + CD38 − CML stem cell–enriched populations were isolated from five patients with chronic phase CML samples by fluorescence-activated cell sorting. To identify BCR–ABL gene mutations, complementary DNAs (cDNAs) prepared from purified CML stem cells were subjected to allele-specific amplification using primers corresponding to 16 kinase domain mutations, with normal bone marrow cells serving as negative controls. We also cloned and directly sequenced BCR–ABL cDNAs prepared from freshly isolated CML stem cells and from their progeny generated after 3–5 weeks of culture. In 20%–33% of cDNA preparations from freshly isolated CML stem cell–enriched populations, both allele-specific amplification and direct sequencing methods revealed mutations in sequences corresponding to the BCR–ABL kinase domain. Mutations were not observed in cDNA sequences encoding the c-ABL kinase domain that were obtained from similar types of primitive normal cells. More than 70 different BCR–ABL mutations (including frameshift mutations and premature stop codons) were identified in the progeny of cultured CML stem cells. Analysis of individual clones derived from the cultured cells demonstrated that new BCR–ABL mutations were produced. Primary CML stem cells display instability of the BCR–ABL fusion gene both in vivo and in vitro. Thus, patients may possess leukemic stem cells with BCR–ABL kinase mutations before initiation of BCR–ABL–targeted therapies and would likely be predisposed to develop resistance to these agents.
Modulation of cholinergic contractions of airway smooth muscle by cathinone: potential beneficial effects in airway diseases
Authors: V. C. Freund-Michel, M. A. Birrell, H. J. Patel, I. M. Murray-Lyon, M. G. Belvisi
Journal: European Respiratory Journal (2008)

Infusion of khat leaves is an African traditional remedy used to treat airway diseases. The beneficial effects of khat are thought to be due to the activity of its main active component, cathinone. Cathinone inhibited electric field stimulation-induced acetylcholine release and the contractions of smooth muscle, which could be responsible for the beneficial effects seen in airway disease. The mechanism of action of this natural product appears to be via the activation of both pre-junctional α 2 adrenergic and 5-hydroxytryptamine 7 receptors. The present novel study describes how cathinone modulates airway tone, and may go some way to explaining the traditional use of khat as a remedy for the alleviation of respiratory disease symptoms. In conclusion, cathinone may have beneficial effects in airway diseases with heightened cholinergic tone. There is some rationale for follow-up of these observations, given previous experience of other traditional remedies being developed for therapeutic use.
Impact of Wall Thickness and Saccular Geometry on the Computational Wall Stress of Descending Thoracic Aortic Aneurysms
Authors: Eric K. Shang, Derek P. Nathan, Shanna R. Sprinkle, Ronald M. Fairman, Joseph E. Bavaria, Robert C. Gorman, Joseph H. Gorman, Benjamin M. Jackson
Journal: Circulation (2013)

Background— Wall stress calculated using finite element analysis has been used to predict rupture risk of aortic aneurysms. Prior models often assume uniform aortic wall thickness and fusiform geometry. We examined the effects of including local wall thickness, intraluminal thrombus, calcifications, and saccular geometry on peak wall stress (PWS) in finite element analysis of descending thoracic aortic aneurysms. Methods and Results— Computed tomographic angiography of descending thoracic aortic aneurysms (n=10 total, 5 fusiform and 5 saccular) underwent 3-dimensional reconstruction with custom algorithms. For each aneurysm, an initial model was constructed with uniform wall thickness. Experimental models explored the addition of variable wall thickness, calcifications, and intraluminal thrombus. Each model was loaded with 120 mm Hg pressure, and von Mises PWS was computed. The mean PWS of uniform wall thickness models was 410±111 kPa. The imposition of variable wall thickness increased PWS (481±126 kPa, P &lt;0.001). Although the addition of calcifications was not statistically significant (506±126 kPa, P =0.07), the addition of intraluminal thrombus to variable wall thickness (359±86 kPa, P ≤0.001) reduced PWS. A final model incorporating all features also reduced PWS (368±88 kPa, P &lt;0.001). Saccular geometry did not increase diameter-normalized stress in the final model (77±7 versus 67±12 kPa/cm, P =0.22). Conclusions— Incorporation of local wall thickness can significantly increase PWS in finite element analysis models of thoracic aortic aneurysms. Incorporating variable wall thickness, intraluminal thrombus, and calcifications significantly impacts computed PWS of thoracic aneurysms; sophisticated models may, therefore, be more accurate in assessing rupture risk. Saccular aneurysms did not demonstrate a significantly higher normalized PWS than fusiform aneurysms.
ECSA/DPPA2 is an Embryo-Cancer Antigen that Is Coexpressed with Cancer-Testis Antigens in Non–Small Cell Lung Cancer
Authors: Thomas John, Otavia L. Caballero, Suzanne J. Svobodová, Alan Kong, Ramon Chua, Judy Browning, Sheila Fortunato, Siddhartha Deb, Melinda Hsu, Craig A. Gedye, Ian D. Davis, Nasser Altorki, Andrew J. Simpson, Yao-Tseng Chen, Marilyn Monk, Jonathan S. Cebon
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cancer cells recapitulate many behaviors of pluripotent embryonic cells such as unlimited proliferation, and the capacity to self-renew and to migrate. Embryo-cancer sequence A (ECSA), later named developmental pluripotency associated-2 (DPPA2), is an embryonic gene initially isolated from pluripotent human preimplantation embryos. We hypothesized that ECSA/DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy. Experimental Design: ECSA/DPPA2 expression was examined in a panel of normal and tumor tissue by reverse transcription PCR, quantitative real-time PCR, and immunohistochemistry. A panel of 110 non–small cell lung cancers (NSCLC) were further investigated for the presence of ECSA/DPPA2 transcripts and several cancer testis antigens (CTA). Sera from 104 patients were analyzed for spontaneous ECSA/DPPA2 antibody production by ELISA and Western blot. Results: ECSA/DPPA2 transcripts were limited to normal testis, placenta, bone marrow, thymus, and kidney but expressed in a variety of tumors most notably in 30% of NSCLC. Enrichment for CTAs in ECSA/DPPA2-positive NSCLC was observed. Immunohistochemistry confirmed nuclear and cytoplasmic localization in subpopulations of cells with coexpression of the CTA MAGE-A3. Antibodies to recombinant ECSA/DPPA2 protein were detected in the sera of 4 of 104 patients with NSCLC but not in healthy controls. Conclusions: The restricted expression in normal tissues, expression in tumors with coexpression of CTAs, and spontaneous immunogenicity indicate that ECSA/DPPA2 is a promising target for antigen-specific immunotherapy in NSCLC.
Telomere Content and Risk of Second Malignant Neoplasm in Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study
Authors: Maria M. Gramatges, Qi Liu, Yutaka Yasui, M. Fatih Okcu, Joseph P. Neglia, Louise C. Strong, Gregory T. Armstrong, Leslie L. Robison, Smita Bhatia
Journal: Clinical Cancer Research (2013)

Shorter constitutional telomere length has been associated with increased cancer incidence. Furthermore, telomere shortening is observed in response to intensive chemotherapy and/or ionizing radiation exposure. We aimed to determine whether less telomere content was associated with treatment-related second malignant neoplasms (SMN) in childhood cancer survivors.Using a nested case-control design, 147 cancer survivors with breast cancer, thyroid cancer, or sarcoma developing after treatment for childhood cancer (cases) were matched (1:1) with childhood cancer survivors without a SMN (controls). Cases and controls were matched by primary cancer diagnosis, years since diagnosis, age at the time of sample collection, years of follow-up from childhood cancer diagnosis, exposure to specific chemotherapy agents, and to specific radiation fields. We performed conditional logistic regression using telomere content as a continuous variable to estimate ORs with corresponding 95% confidence intervals (CI) for development of SMN. ORs were also estimated for specific SMN types, i.e., breast cancer, thyroid cancer, and sarcoma.There was an inverse relationship between telomere content and SMN, with an adjusted OR of 0.3 per unit change in telomere length to single-copy gene ratio (95% CI, 0.09-1.02; P = 0.05). Patients with thyroid cancer SMN were less likely to have more telomere content (OR, 0.04; 95% CI, 0.00-0.55; P = 0.01), but statistically significant associations could not be demonstrated for breast cancer or sarcoma.A relation between less telomere content and treatment-related thyroid cancer was observed, suggesting that shorter telomeres may contribute to certain SMNs in childhood cancer survivors.