tbuckley/cabot-search huggingface dataset:
Mitochondrial DNA Sequence Diversity in Bipolar Affective Disorder
Authors: F J McMahon, Y S Chen, S Patel, J Kokoszka, M D Brown, A Torroni, J R DePaulo, D C Wallace
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Point mutations in mitochondrial DNA (mtDNA) are one mechanism that could explain the apparent excess maternal transmission of bipolar affective disorder observed in some families. The authors sequenced the mtDNA from probands with bipolar disorder and tested nucleotide variants for association with the disorder.METHOD: The entire 16.5 kilobase mitochondrial genome was sequenced in nine unrelated probands selected from large pedigrees with exclusively maternal transmission of bipolar affective disorder. Compared to a reference sequence, variants were detected at 107 nucleotide positions. Fifteen variants of possible pathogenic significance were selected for further study. These variants were assayed in 93 unrelated probands with bipolar I, bipolar II, or schizoaffective-manic disorder and 63 comparison subjects, all of whom were classified into the major groups comprising the European mtDNA haplotype structure (haplogroups).RESULTS: The major European haplogroups were represented at the expected frequencies among both probands and comparison subjects. There was no significant difference between probands and comparison subjects in the frequency of any variant, although odds ratios >2 or <0.5 were observed for four variants. Frequencies of these four variants were similar in probands and haplogroup-matched comparison subjects. The results of all comparisons were essentially unchanged when probands from families with an apparently paternal transmission pattern were excluded.CONCLUSIONS: The results demonstrate that bipolar affective disorder occurs across all of the major European mtDNA haplogroups but do not reveal any point mutations that explain excess maternal transmission of the disorder.
Endocardial versus epicardial differences of intracellular free calcium under normal and ischemic conditions in perfused rat hearts.
Authors: V M Figueredo, R Brandes, M W Weiner, B M Massie, S A Camacho
Journal: Circulation Research (1993)

Transmural heterogeneity of myocardial metabolism and function are present in the left ventricle under normal and ischemic conditions. To determine if endocardial versus epicardial differences of [Ca2+]i are also present, perfused rat heart studies using indo-1 fluorescence as an index of [Ca2+]i were performed in the left ventricular epicardium and endocardium. Hearts were studied during control conditions and low-flow ischemia. Results demonstrated the following: 1) At a pacing rate of 1.5 Hz, endocardial levels of diastolic and systolic [Ca2+]i (470 +/- 40 and 1,240 +/- 170 nM) were higher than epicardial levels (290 +/- 30 and 920 +/- 150 nM). 2) At a more physiological pacing rate of 5 Hz, endocardial levels of diastolic and systolic [Ca2+]i (680 +/- 50 and 1,230 +/- 70 nM) were also higher than epicardial levels (390 +/- 20 and 950 +/- 60 nM. 3) During low-flow ischemia, endocardial levels of diastolic [Ca2+]i rose to a greater degree (from 680 +/- 50 to 1,050 +/- 70 nM at 10% of control coronary flow) compared with epicardial levels (from 390 +/- 20 to 580 +/- 40 nM at 10% of control flow), suggesting that the endocardium is more susceptible to low-flow ischemia. 4) The amplitude of the [Ca2+]i transient was the same at the endocardium (540 +/- 50 nM) and epicardium (560 +/- 50 nM) and did not change during low-flow ischemia, despite marked contractile dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
Phylogeny of the Drosophila saltans species group based on combined analysis of nuclear and mitochondrial DNA sequences
Authors: P. M. O'Grady, J. B. Clark, M. G. Kidwell
Journal: Molecular Biology and Evolution (1998)

Nucleotide sequences from two nuclear loci, alcohol dehydrogenase and internal transcribed spacer-1 of the nuclear ribosomal DNA repeats, and two mitochondrial genes, cytochrome oxidase I and cytochrome oxidase II, were determined from nine species in the Drosophila saltans species group. The partition homogeneity test and partitioned Bremer support were used to measure incongruence between phylogenetic hypotheses generated from individual partitions. Individual loci were generally congruent with each other and consistent with the previously proposed morphological hypothesis, although they differed in level of resolution. Since extreme conflict between partitions did not exist, the data were combined and analyzed simultaneously. The total evidence method gave a more resolved and highly supported phylogeny, as indicated by bootstrap proportions and decay indices, than did any of the individual analyses. The cordata and elliptica subgroups, considered to have diverged early in the history of the D. saltans group, were sister taxa to the remainder of the saltans group. The sturtevanti subgroup, represented by D. milleri and D. sturtevanti, occupies an intermediate position in this phylogeny. The saltans and parasaltans subgroups are sister clades and occupy the most recently derived portion of the phylogeny. As with previous morphological studies, phylogenetic relationships within the saltans subgroup were not satisfactorily resolved by the molecular data.
Behaviour and control of influenza in institutions and small societies
Authors: Thomas James Ronald Finnie, Ian M Hall, Steve Leach
Journal: Journal of the Royal Society of Medicine (2012)

A literature review was undertaken to assess the impact of influenza in enclosed societies. The literature spanned 120 years and included both readily accessible material from online keyword searches, as well as more obscure paper documents found through in-depth library research. Enclosed societies have been predominantly found in some type of institution through this period although noticeable similarities exist in communities isolated by distance and geography. We observe that no matter how isolated a community is, it is not necessarily insulated from infection by influenza and that even where there are no complicating factors, such as the age distribution or the presence of individuals with greater susceptibility in the enclosed population, their organization tends to increase influenza transmission and the risk of secondary infection. The collected accounts demonstrate important features of outbreaks in such societies and the necessity of considering them in pandemic planning: in particular, rapid intervention is essential for the control of influenza spread in such circumstances. Recent experience has shown that administration of modern antiviral drugs, such as neuraminidase inhibitors are effective at moderating outbreaks of influenza, but only in combination with other methods of control. In more remote communities where such drugs are not, or less, readily available, and medical care is limited, such outbreaks can still pose particular difficulties. In all cases delay in correct diagnosis, detection of an outbreak or the implementation of control measures can result in the majority of the enclosed population succumbing to the disease.
Structural and functional differences between the H-2 controlled Ss and Slp proteins.
Authors: A Ferreira, V Nussenzweig, I Gigli
Journal: The Journal of Experimental Medicine (1978)

Based on functional and structural data, it is concluded that the Ss protein in the mouse expresses the activity of the fourth component of complement. Removal of the Ss, but not of Slp, antigen correlates with a high degree of significance (P less than 0.001) with decrease of C4 hemolytic activity. In phenotypically Slp negative mice the plasma/serum levels of Ss correlate with the C4 activity (P less than 0.001). Structurally, Ss is a 209,000-mol wt protein, consisting of three covalently linked polypeptide chains (alpha,beta,gamma). Treatment of Ss with C1 cleaves a 7,000-8,000-mol wt fragment from the alpha-chain. Slp is also a three chain covalently linked protein of 209,000 daltons, however its three chains differ in size from those of the Ss protein. Slp does not express hemolytic activity and its alpha-chain is not cleaved by C1.
Rescue of Hippo coactivator YAP1 triggers DNA damage–induced apoptosis in hematological cancers
Authors: Francesca Cottini, Teru Hideshima, Chunxiao Xu, Martin Sattler, Martina Dori, Luca Agnelli, Elisa ten Hacken, Maria Teresa Bertilaccio, Elena Antonini, Antonino Neri, Maurilio Ponzoni, Magda Marcatti, Paul G Richardson, Ruben Carrasco, Alec C Kimmelman, Kwok-Kin Wong, Federico Caligaris-Cappio, Giovanni Blandino, W Michael Kuehl, Kenneth C Anderson, Giovanni Tonon
Journal: Nature Medicine (2014)
Hepatocyte Growth Factor/cMET Pathway Activation Enhances Cancer Hallmarks in Adrenocortical Carcinoma
Authors: Liem M. Phan, Enrique Fuentes-Mattei, Weixin Wu, Guermarie Velazquez-Torres, Kanishka Sircar, Christopher G. Wood, Tao Hai, Camilo Jimenez, Gilbert J. Cote, Levent Ozsari, Marie-Claude Hofmann, Siyuan Zheng, Roeland Verhaak, Lance Pagliaro, Maria Angelica Cortez, Mong-Hong Lee, Sai-Ching J. Yeung, Mouhammed Amir Habra
Journal: Cancer Research (2015)

Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in adrenocortical carcinoma has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of adrenocortical carcinoma. Transcriptomic and immunohistochemical analyses indicated that increased HGF/cMET expression in human adrenocortical carcinoma samples was positively associated with cancer-related biologic processes, including proliferation and angiogenesis, and negatively correlated with apoptosis. Accordingly, treatment of adrenocortical carcinoma cells with exogenous HGF resulted in increased cell proliferation in vitro and in vivo while short hairpin RNA-mediated knockdown or pharmacologic inhibition of cMET suppressed cell proliferation and tumor growth. Moreover, exposure of cells to mitotane, cisplatin, or radiation rapidly induced pro-cMET expression and was associated with an enrichment of genes (e.g., CYP450 family) related to therapy resistance, further implicating cMET in the anticancer drug response. Together, these data suggest an important role for HGF/cMET signaling in adrenocortical carcinoma growth and resistance to commonly used treatments. Targeting cMET, alone or in combination with other drugs, could provide a breakthrough in the management of this aggressive cancer.
Every breath you take
Authors: A. R. Glanville
Journal: Thorax (2011)

To paraphrase the ubiquitous warning applied to the perverse products of the tobacco industry, ‘breathing may be dangerous to your health’, in particular if you are a lung transplant recipient. This is especially true if you live near a major road in a region with high levels of traffic-related air pollution. Alone among solid organ transplants, the lung allograft is exposed to the ambient environment with every breath. Some environments are toxic, some more so, and the paper by Nawrot et al in Thorax presents a compelling argument that traffic air pollution is a strong component of the toxic environmental risk which has measurable and deleterious effects on pulmonary allograft function and recipient survival, accounting for 28% of deaths.1 Specifically, this landmark study reports for the first time the relationship between traffic air pollution and the development of the bronchiolitis obliterans syndrome (BOS) in a large and well-characterised sample of lung transplant recipients from a region where air pollution levels are high by global standards. BOS is the major risk factor for death after lung transplantation, so it is not surprising that exposure to air traffic pollution, defined by residential proximity to a major road, was also a risk factor for death after transplantation. Importantly, other potential risk factors were rigorously examined to prevent confounding and the relationship was highly significant regardless of whether distance categories from a main road were expressed as a …
Current Issues in the Diagnosis of Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder
Authors: Paul J. Frick, Joel T. Nigg
Journal: Annual Review of Clinical Psychology (2012)

This review evaluates the diagnostic criteria for three of the most common disorders for which children and adolescents are referred for mental health treatment: attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). Although research supports the validity and clinical utility of these disorders, several issues are highlighted that could enhance the current diagnostic criteria. For ADHD, defining the core features of the disorder and its fit with other disorders, enhancing the validity of the criteria through the lifespan, considering alternative ways to form subtypes of the disorder, and modifying the age-of-onset criterion are discussed relative to the current diagnostic criteria. For ODD, eliminating the exclusionary criteria of CD, recognizing important symptom domains within the disorder, and using the cross-situational pervasiveness of the disorder as an index of severity are highlighted as important issues for improving classification. Finally, for CD, enhancing the current subtypes related to age of onset and integrating callous-unemotional traits into the diagnostic criteria are identified as key issues for improving classification.
G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome
Authors: A. Aggarwal, C.S. Baker, T.W Evans, P.L Haslam
Journal: European Respiratory Journal (2000)

Activated neutrophils play a major role in the pathogenesis of acute respiratory distress syndrome (ARDS), and persistence of pulmonary neutrophilia is related to poor survival. Interleukin (IL)-8 is implicated in recruiting neutrophils to the lungs but it has been postulated that granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), which can promote the survival of neutrophils by delaying apoptosis, may prolong the inflammatory response. The aim of this study was to investigate the levels of GM-CSF and G-CSF in the lungs of patients with ARDS and determine their relationship relative to IL-8 with levels of neutrophils and clinical outcome. The lungs of 31 patients with ARDS were sampled by means of bronchoalveolar lavage (BAL) and assays of the three cytokines were conducted via enzyme-linked immunosorbent assay. GM-CSF, G-CSF and IL-8 were all increased in the patients compared to healthy controls but concentrations of GM-CSF were much lower than those of G-CSF and IL-8 (GM-CSF&lt;G-CSF&lt;IL-8). Levels of G-CSF and IL-8, but not GM-CSF, correlated strongly with each other (rS=0.86, p&lt;0.001) and with BAL neutrophil counts, and only levels of G-CSF were significantly higher in nonsurvivors than survivors (p&lt;0.05). This evidence indicates that granulocyte colony-stimulating factor as well as interleukin-8 plays a role in the mechanisms of pulmonary neutrophilia in acute respiratory distress syndrome, whereas the role of granulocyte-macrophage colony-stimulating factor remains unclear. The higher levels of granulocyte colony-stimulating factor in nonsurvivors, together with previous reports that recombinant granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor occasionally induce acute lung injury, emphasize that the role of these mediators in pathogenesis needs to be elucidated.
Prognostic value of grading in neuroendocrine tumours
Authors: None Khan, F. El-Khouly, C. Toumpanakis, M. Caplin, T. V. Luong
Journal: Gut (2011)

<h3>Introduction</h3> Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are uncommon tumours but with an increasing prevalence (35 per 100 000). They are generally slow-growing but have variable proliferation indices. The recent classification system of NETs proposed by the European Neuroendocrine Tumour Society (ENETS) uses Ki-67 index and/or mitotic count to assign grade (low, intermediate, high)1. We have previously demonstrated a discrepancy in grade assignment depending on whether Ki-67 or mitotic count is used2. It has been adopted into routine practice but there is limited data on the relationship between these indices and whether they have similar prognostic value. We explored the prognostic value of grading according to Ki-67 and mitotic count in GEP NETs. <h3>Methods</h3> 285 NET patients, 144 midgut and 141 pancreatic, had their cases reviewed. Ki-67 proliferation index, identified by staining tumour sections with MIB-1 antibody, was determined by assessing the percentage of positively staining tumour cell nuclei in 2000 tumour cells. Mitotic counts (per 10 high power fields) were evaluated in at least 40 fields in areas of highest mitotic activity. Grades (1 to 3) according to the new TNM classification were assigned using both indices. Slides were assessed by an experienced pathologist with expertise in NETs. Progression-free survival (PFS) and overall survival (OS) from date of diagnosis were estimated using Kaplan–Meier methodology and Cox Regression used for multivariate analysis. <h3>Results</h3> 131/144 midgut and 136/141 pancreatic NETs had complete data. As previously reported, there was discordance in grade assignment (38% and 51% respectively). Median follow-up was 42 months in midgut and 46 months in pancreatic NETs. 5-year PFS and OS for pancreatic NETs were 29% and 53% respectively. 5-year PFS and OS for midgut NETs were 37% and 61%. On univariate analysis, grade according to either Ki-67 or mitotic count was prognostic of PFS and OS in both types of NETs. On multivariate analysis, grade according to Ki-67 was an independent prognostic indicator of PFS and OS (p&lt;0.001). Grade according to mitotic count was not (p&gt;0.16). <h3>Conclusion</h3> Grade according to Ki-67 is of prognostic significance but grade assigned by mitotic count may not provide similar prognostic value based on the current classification thresholds. Further studies evaluating grading thresholds of mitotic counts and investigation of other mitotic markers are required.
Intranasal Cold Dry Air Is Superior to Histamine Challenge in Determining the Presence and Degree of Nasal Hyperreactivity in Nonallergic Noninfectious Perennial Rhinitis
Authors: JOSEPH P. M. BRAAT, PAUL G. MULDER, WYTSKE J. FOKKENS, ROY GERTH van WIJK, EVERT RIJNTJES
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The objective of the study was to compare cold dry air (CDA) and histamine in differentiating patients with nonallergic noninfectious perennial rhinitis (NANIPER) from control subjects. Nasal reactivity (nasal patency, mucus production, and sneezing) in 16 symptomatic nonsmoking patients with NANIPER and seven nonsmoking control subjects was measured with standardized CDA and histamine provocation series in a randomized crossover study. Intranasal CDA resulted in increased mucus production and nasal blockage in a dose-dependent manner in patients with NANIPER but not in control subjects. Sneezing did not occur. The reproducibility of CDA for patency and mucus production was good. Sensitivity for CDA was 87% compared with 100% for histamine. However, specificity was 71% for CDA and 0% for histamine. It is concluded that the new standardized intranasal CDA provocation method uses a recognizable natural nonspecific stimulus and seems to be more suitable than histamine for characterizing and assessing the presence and degree of nasal reactivity in NANIPER.
Bariatric Surgery Does Not Exacerbate and May Be Beneficial for the Microvascular Complications of Type 2 Diabetes
Authors: Alexander D. Miras, Ling Ling Chuah, Gerassimos Lascaratos, Sana Faruq, Ajay A. Mohite, Priya R. Shah, Mahi Gill, Sabrina N. Jackson, Desmond G. Johnston, Torsten Olbers, Carel W. le Roux
Journal: Diabetes Care (2012)

The effects of bariatric surgery on microvascular complications remain underexplored despite more than 40 years of surgery on patients with type 2 diabetes. The literature has focused predominantly on glycemic control and very little on diabetes-related complications, which confer high rates of morbidity and mortality. Our aim was to assess whether the gastric bypass, sleeve gastrectomy, and gastric banding procedures are safe for the retinal and renal complications of type 2 diabetes, especially as they lead to rapid improvements in glycemia, which may paradoxically cause or exacerbate microvascular complications.

Prospectively collected retinal photographs (two-field) and urine albumin creatinine ratios (ACRs) were analyzed retrospectively in 84 consecutive patients with type 2 diabetes before and 12–18 months after surgery. The results were confirmed by an independent ophthalmologist who was blinded to clinical information. Improvement or deterioration was defined as a decrease or increase of at least two …
Preparation and evaluation of taste masked oral suspension of arbidol hydrochloride
Authors: Ling Wang, Yinghua Sun, Chen Kuang, Xiangrong Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The purpose of this study was to cover the bitter taste of arbidol hydrochloride (ARB) and develop dry suspension with combination of solid dispersion and flavors. Taste masking was successfully done by solid dispersion using octadecanol as the carrier by fusion method. Suspending agents, carriers and other excipients were selected. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were performed to identify the physicochemical interaction between drug and carrier, DSC analysis indicated that ARB was amorphous in the solid dispersion, FTIR spectroscopy showed no interaction between drug and carrier. Taste masking was evaluated on six volunteers with a score of 4.9. The results demonstrated successful taste masking. Water was used to study the in vitro dissolution performance of the three formulations of commercial tablet, capsule and self-made suspension. The self-made suspension showed a lower and slower release, the insoluble carrier octadecanol blocked the drug dissolving from the solid dispersion. It was indicated from the primary stability study, the self-made suspensions were sensitive to high temperature, high humidity and strong light conditions, they should be stored in sealed containers away from heat, light and humidity.
Effect of Elevated Left Atrial Pressure and Decreased Plasma Protein Concentration on the Development of Pulmonary Edema
Authors: ARTHUR C. GUYTON, ARTHUR W. LINDSEY, HOWELL, JOHNNIE O., WILLIAMS JOHN W., FRANKLIN MALCOLM A.
Journal: Circulation Research (1959)

In 97 dogs left atrial pressure was elevated to various levels up to 50 mm. Hg by partial constriction of the aorta. The effect of these pressures for from 30 min. to 3 hours on the accumulation of lung edema was then studied. Edema was estimated by determining the ratio of the weight of the wet lung to the weight of the same lung after drying. In animals with normal plasma protein concentrations fluid began to transude into the lungs when the left atrial pressure rose above an average of 24 mm. Hg. In another series of animals the plasma protein concentrations were reduced by plasmapheresis at the beginning of each experiment until the plasma protein concentration averaged 47 per cent of the control value. In these animals fluid began to transude into the lungs when the left atrial pressure rose above a critical value of 11 mm Hg. Furthermore, the rate at which fluid accumulated in the lungs, in all series of experiments, was directly proportional to the rise in left atrial pressure above the critical pressure at which fluid began to collect in the lungs.