tbuckley/cabot-search huggingface dataset:
Inhibition of Delta-Like-4–Mediated Signaling Impairs Reparative Angiogenesis After Ischemia
Authors: Ayman Al Haj Zen, Atsuhiko Oikawa, Miriam Bazan-Peregrino, Marco Meloni, Costanza Emanueli, Paolo Madeddu
Journal: Circulation Research (2010)

Notch signaling regulates vascular development. However, the implication of the Notch ligand Delta-like 4 (Dll4) in postischemic angiogenesis remains unclear.We investigated the role of Dll4/Notch signaling in reparative angiogenesis using a mouse model of ischemia.We found Dll4 weakly expressed in microvascular endothelial cells of normoperfused muscles. Conversely, Dll4 is upregulated following ischemia and localized at the forefront of sprouting capillaries. We analyzed the effect of inhibiting endogenous Dll4 by intramuscular injection of an adenovirus encoding the soluble form of Dll4 extracellular domain (Ad-sDll4). Dll4 inhibition caused the formation of a disorganized, low-perfused capillary network in ischemic muscles. This structural abnormality was associated to delayed blood flow recovery and muscle hypoxia and degeneration. Analysis of microvasculature at early stages of repair revealed that Dll4 inhibition enhances capillary sprouting in a chaotic fashion and causes excessive leukocyte infiltration of ischemic muscles. Furthermore, Dll4 inhibition potentiated the elevation of the leukocyte chemoattractant CXCL1 (chemokine [C-X-C motif] ligand 1) following ischemia, without altering peripheral blood levels of stromal cell-derived factor-1 and monocyte chemoattractant protein-1. In cultured human monocytes, Dll4 induces the transcription of Notch target gene Hes-1 and inhibits the basal and tumor necrosis factor-alpha-stimulated production of interleukin-8, the human functional homolog of murine CXCL1. The inhibitory effect of Dll4 on interleukin-8 was abolished by DAPT, a Notch inhibitor, or by coculturing activated human monocytes with Ad-sDll4-infected endothelial cells.Dll4/Notch interaction is essential for proper reparative angiogenesis. Moreover, Dll4/Notch signaling regulates sprouting angiogenesis and coordinates the interaction between inflammation and angiogenesis under ischemic conditions.
A Study of the Withdrawal of Chlorpromazine or Trifluoperazine in Chronic Schizophrenia
Authors: M. R. MORTON
Journal: American Journal of Psychiatry (1968)

Because the importance of tranquilizing drugs has been difficult to assess precisely, the author undertook a study on the effect of the withdrawal of chlorpromazine and trifluoperazine on hospitalized male schizophrenics in England. Although there were no major relapses among the placebo group, changes occurred that were sometimes disabling.
How to make a good oocyte: an update on in-vitro models to study follicle regulation
Authors: F. H. Thomas, K. A. Walters, E. E. Telfer
Journal: Human Reproduction Update (2003)

The ability to develop the technology to mature oocytes from immature oocytes in vitro is the ambition of many IVF clinics. If this can be successfully achieved then these techniques would be available to women with fertility problems. This would aid women at risk of premature ovarian failure, and possibly result in women no longer requiring an expensive drug regime and monitoring programme, which they currently have to undergo. The idea of harvesting immature oocytes for growth in vitro is not a new one, but progress has been slow in developing and optimizing techniques for use on humans and domestic species. At present, there are many technical reasons for the lack of progress in these species, such as length of culture and difficulty of follicle isolation. However, the major problem is our lack of knowledge of how the oocyte acquires developmental competence during its growth within the follicle. To date, culture systems have been developed that can support the growth and development of immature oocytes. These systems are beneficial in improving our knowledge of how autocrine/paracrine factors are involved in regulating and controlling oocyte development. However, only when we have a more in‐depth understanding of what is required during development to make a viable oocyte, will we perhaps be able to develop in‐vitro culture systems for clinical application. This review will focus on how analysis of early follicular growth and development, using in‐vitro culture systems, has advanced our knowledge of the factors and process involved in the regulation of oocyte and somatic cell development.
Effects of Experimental Congestive Heart Failure, Ouabain, and Asphyxia on the High-Energy Phosphate and Creatine Content of the Guinea Pig Heart
Authors: MAURICE B. FEINSTEIN
Journal: Circulation Research (1962)

The left ventricles of guinea pigs have been assayed for adenosine triphosphate, adenosine diphosphate, adenylic acid, phosphorylcreatine, free creatine, and inorganic phosphate. These determinations have been made under various experimental conditions which affect the performance of the heart in vivo, such as experimental congestive heart failure, acute asphyxia, and the influence of the cardiac glycoside, ouabain. In 20 guinea pigs with experimental congestive heart failure, sacrificed 1 to 18 days after surgically producing a coarctation of the ascending aorta, a significant fall in PC (54 per cent), ATP (24 per cent), and total creatine (34 per cent) was observed. The extent of the loss of high-energy phosphate compounds and total creatine paralleled the severity of cardiac failure as determined by abnormal intraventricular pressure pulses, ventricular hypertrophy, and gross and microscopic pathology. In animals with experimental congestive heart failure, the cardiac glycoside ouabain produced significant slowing of the heart, a positive inotropic effect, and a lowering of abnormally high right ventricular systolic and left ventricular diastolic pressures. At the height of the response to ouabain, there was a further fall in PC to 25 per cent of normal without any change in ATP concentration. The positive inotropic action of ouabain is, therefore, not due to an ability of the drug to increase high-energy phosphate levels in failing heart muscle. Acute asphyxia produces a very rapid fall in the PC concentration (85 per cent lost in two minutes) and a much slower fall in ATP (33 per cent lost in eight minutes). Recovery of normal mechanical activity, after a period of asphyxia, by rebreathing occurs with little, if any, restoration of ATP and at a time when the PC concentration is only about 25 per cent of normal. These experiments indicate that steady-state levels of high-energy phosphate compounds are not as important in determining the mechanical capacity of the heart as are their rates of synthesis.
Evolution of Gene Expression in the Drosophila Olfactory System
Authors: A. Kopp, O. Barmina, A. M. Hamilton, L. Higgins, L. M. McIntyre, C. D. Jones
Journal: Molecular Biology and Evolution (2008)

Host plant shifts by phytophagous insects play a key role in insect evolution and plant ecology. Such shifts often involve major behavioral changes as the insects must acquire an attraction and/or lose the repulsion to the new host plant's odor and taste. The evolution of chemotactic behavior may be due, in part, to gene expression changes in the peripheral sensory system. To test this hypothesis, we compared gene expression in the olfactory organs of Drosophila sechellia, a narrow ecological specialist that feeds on the fruit of Morinda citrifolia, with its close relatives Drosophila simulans and Drosophila melanogaster, which feed on a wide variety of decaying plant matter. Using whole-genome microarrays and quantitative polymerase chain reaction, we surveyed the entire repertoire of Drosophila odorant receptors (ORs) and odorant-binding proteins (OBPs) expressed in the antennae. We found that the evolution of OR and OBP expression was accelerated in D. sechellia compared both with the genome average in that species and with the rate of OR and OBP evolution in the other species. However, some of the gene expression changes that correlate with D. sechellia's increased sensitivity to Morinda odorants may predate its divergence from D. simulans. Interspecific divergence of olfactory gene expression cannot be fully explained by changes in the relative abundance of different sensilla as some ORs and OBPs have evolved independently of other genes expressed in the same sensilla. A number of OR and OBP genes are upregulated in D. sechellia compared with its generalist relatives. These genes include Or22a, which likely responds to a key odorant of M. citrifolia, and several genes that are yet to be characterized in detail. Increased expression of these genes in D. sechellia may have contributed to the evolution of its unique chemotactic behavior.
Hypoxia, electrical uncoupling, and conduction slowing: Role of conduction reserve
Authors: H VANRIJEN, J DEBAKKER, T VANVEEN
Journal: Cardiovascular Research (2005)

See article by Zeevi-levin et al.  [7]  (pages 64–73) in this issue. 

Cardiac activation is based on propagation of the action potential and requires low resistance cell–cell coupling and proper excitability. The electrical coupling between myocytes is mediated by protein channels, called gap junctions, consisting of connexins (Cx, in the ventricle mainly Cx43). Sodium channels (SCN5A) are the major channel proteins involved in excitability of the cardiac cells. A third factor that determines conduction velocity is the tissue architecture, which involves cell shape [1] and interstitial collagen content (fibrosis) [2]. Many cardiac pathologies change these determinants, which give rise to slow and abnormal conduction and increases the propensity for arrhythmias.

Myocardial ischemia is strongly associated with arrhythmias [3]. One of the mechanisms responsible for the arrhythmogenic substrate under conditions of myocardial ischemia is electrical uncoupling at gap junctions (for a review see [4]). It has been shown that upregulation of gap junctional conductance during myocardial ischemia reduces the occurrence of reentrant arrhythmias [5], but not of focal tachycardias [6].

The study of Zeevi-Levin ( Cardiovascular Research , this issue) supports the concept of uncoupling-induced conduction slowing [7]. These investigators have used an in vitro conduction assay in which rat neonatal cardiomyocytes are cultured on top of a micro-electrode array. This experimental setup allows determination of conduction in great detail before and after intervention, during a long period. A disadvantage … 

*Corresponding author. Tel.: +31 302538900; fax: +31 302539036. Email address: H.V.M.vanRijen{at}med.uu.nl
Dipaxin—2-Diphenylacetyl-1,3-Indandione; Clinical Evaluation of a New Anticoagulant
Authors: JOHN B. FIELD, MARTIN S. GOLDFARB, ARNOLD G. WARE, GEORGE C. GRIFFITH
Journal: Circulation (1955)

In the course of development of new anticoagulants, an indandione derivative has been subjected to a clinical evaluation. The new agent is one of the most potent hypoprothrombinemic substance known but it is readily counteracted with vitamin K. The agent was administered to a large series of patients with thromboembolic diseases and control of anticoagulant therapy was observed to be simple, reproducible, with a good predictability of response as well as with absence of toxic phenomena and a low order of bleeding complications. It has been administered to 11 patients for ambulant anticoagulant care for periods up to 18 months with satisfactory results and it appears to be especially suitable for long-term maintenance therapy.
Scoliosis: muscle imbalance and treatment
Authors: Zoran Šarčević
Journal: British Journal of Sports Medicine (2010)

The aim of this study was to detect muscle imbalance on both sides of the backbone, and with muscle strength training, to correct this imbalance and, as a final result, to eliminate scoliosis of the spine. Forty-seven children (32 girls and 15 boys), aged 10–16 years, were examined. Muscle strength tests showed that m. quadratus lumborum and m. gluteus medius on the convex side of the spinal curvature appeared to be weaker compared to concave side, and m. erector spine lumbalis and m. multifidus on the concave side of the spinal curvature appeared to be weaker compared to convex side. In the thoracic region, m. trapezius medius, m. trapezius distalis and m. serratus anterior on the convex side appeared to be weaker compared to concave side, and m. rhomboideus on the concave side appeared to be weaker compared to convex side. Apart from intense muscle training for strengthening of weak back muscle groups, all patients were instructed to do the abdominal muscle exercises. This treatment lasted from 2 to 6 months. Using this method of intense muscle training, scoliosis was eliminated with a non-surgical treatment.
Superoxide-mediated activation of uncoupling protein 2 causes pancreatic β cell dysfunction
Authors: Stefan Krauss, Chen-Yu Zhang, Luca Scorrano, Louise T. Dalgaard, Julie St-Pierre, Shane T. Grey, Bradford B. Lowell
Journal: Journal of Clinical Investigation (2003)

Failure to secrete adequate amounts of insulin in response to increasing concentrations of glucose is an important feature of type 2 diabetes. The mechanism for loss of glucose responsiveness is unknown. Uncoupling protein 2 (UCP2), by virtue of its mitochondrial proton leak activity and consequent negative effect on ATP production, impairs glucose-stimulated insulin secretion. Of interest, it has recently been shown that superoxide, when added to isolated mitochondria, activates UCP2-mediated proton leak. Since obesity and chronic hyperglycemia increase mitochondrial superoxide production, as well as UCP2 expression in pancreatic β cells, a superoxide-UCP2 pathway could contribute importantly to obesity- and hyperglycemia-induced β cell dysfunction. This study demonstrates that endogenously produced mitochondrial superoxide activates UCP2-mediated proton leak, thus lowering ATP levels and impairing glucose-stimulated insulin secretion. Furthermore, hyperglycemia- and obesity-induced loss of glucose responsiveness is prevented by reduction of mitochondrial superoxide production or gene knockout of UCP2. Importantly, reduction of superoxide has no beneficial effect in the absence of UCP2, and superoxide levels are increased further in the absence of UCP2, demonstrating that the adverse effects of superoxide on β cell glucose sensing are caused by activation of UCP2. Therefore, superoxide-mediated activation of UCP2 could play an important role in the pathogenesis of β cell dysfunction and type 2 diabetes.
Olanzapine Versus Divalproex Sodium for the Treatment of Acute Mania and Maintenance of Remission: A 47-Week Study
Authors: Mauricio Tohen, Terence A. Ketter, Carlos A. Zarate, Trisha Suppes, Mark Frye, Lori Altshuler, John Zajecka, Leslie M. Schuh, Richard C. Risser, Eileen Brown, Robert W. Baker
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex. METHOD: This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5–20 mg/day) to divalproex (500–2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were ≥20 for inclusion, ≤12 for remission, and ≥15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest. RESULTS: Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness. CONCLUSIONS: In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.
Cell Proliferation in the Loop of Henle in the Developing Rat Kidney
Authors: JUNG-HO CHA, YOUNG-HEE KIM, JU-YOUNG JUNG, KI-HWAN HAN, KIRSTEN M. MADSEN, JIN KIM
Journal: Journal of the American Society of Nephrology (2001)

Abstract. In the developing rat kidney, there is no separation of the medulla into an outer and inner zone. At the time of birth, ascending limbs with immature distal tubule epithelium are present throughout the renal medulla, all loops of Henle resemble the short loop of adult animals, and there are no ascending thin limbs. It was demonstrated previously that immature thick ascending limbs in the renal papilla are transformed into ascending thin limbs by apoptotic deletion of cells and transformation of the remaining cells into a thin squamous epithelium. However, it is not known whether this is the only source of ascending thin limb cells or whether cell proliferation occurs in the segment undergoing transformation. This study was designed to address these questions and to identify sites of cell proliferation in the loop of Henle. Rat pups, 1, 3, 5, 7, and 14 d old, received a single injection of 5-bromo-2′-deoxyuridine (BrdU) 18 h before preservation of kidneys for immunohistochemistry. Thick ascending and descending limbs were identified by labeling with antibodies against the serotonin receptor, 5-HT 1A , and aquaporin-1, respectively. Proliferating cells were identified with an antibody against BrdU. BrdU-positive cells in descending and ascending limbs of the loop of Henle were counted and expressed as percentages of the total number of aquaporin-1—positive and 5-HT 1A —positive cells in the different segments. In the developing kidney, numerous BrdU-positive nuclei were observed in the nephrogenic zone. Outside of this location, BrdU-positive tubule cells were most prevalent in medullary rays in the inner cortex and in the outer medulla. BrdU-labeled cells were rare in the papillary portion of the loop of Henle and were not observed in the lower half of the papilla after 3 d of age. BrdU-labeled nuclei were not observed in segments undergoing transformation or in newly formed ascending thin limb epithelium. It was concluded that the growth zone for the loop of Henle is located around the corticomedullary junction, and the ascending thin limb is mainly, if not exclusively, derived from cells of the thick ascending limb.
Preventing ventricular dysfunction in pacemaker patients without advanced heart failure: results from a multicentre international randomized trial (PREVENT‐HF)
Authors: Martin Stockburger, Juan José Gómez‐Doblas, Gervasio Lamas, Javier Alzueta, Ignacio Fernández‐Lozano, Erik Cobo, Uwe Wiegand, Joaquín Fernández de la Concha, Xavier Navarro, Francisco Navarro‐López, Eduardo de Teresa
Journal: European Journal of Heart Failure (2011)
Effect of PM10 on H. influenzae and S. pneumoniae.
Authors: A. Adedeji, T. M. Weller, Jonathan Geoffrey Ayres
Journal: Thorax (2004)

That air pollution, and specifically particles, are harmful to health is well accepted,1 causing direct effects such as lung inflammation resulting in exacerbations of lung and cardiac conditions2,3 and being associated with admissions for pneumonia. In the 1960s Lawther et al showed that ambient particles stimulated the growth of Haemophilus influenzae in vitro,4 suggesting a direct effect of particles on bacteria themselves. However, it is not known whether this remains so for modern ambient particles where the sources are different.

To address this we have assessed the effect of PM10 (particles essentially less than 10 μm in diameter) on the respiratory pathogens commonly associated with acute exacerbations of chronic obstructive pulmonary disease (COPD) and pneumonia. The effect of dilutions of extracts of PM10 on the growth of H influenzae and Streptococcus pneumoniae grown in liquid broth and the effect of PM10 on microbial growth kinetics of S pneumoniae was assessed.

Fresh isolates of H influenzae and S pneumoniae obtained from clinical …
Abdominal pain following percutaneous mitral valve repair (MitraClip)
Authors: Albrecht Neesse, Wilhelm Nimphius, Michael Schoppet, Thomas M Gress
Journal: Gut (2014)

An 81-year-old man underwent percutaneous mitral valve repair (MitraClip) due to severe symptomatic mitral valve regurgitation. Coronary heart disease was excluded prior to mitral valve repair. Approximately 8 h after the uneventful and successful intervention, the patient presented with progressive abdominal pain, in particular tenderness in the right upper quadrant with guarding. Laboratory tests did not reveal any acute alterations; serum lactate was 2.4 mmol/L. Bedside ultrasonography showed a distended ascending colon with a pronounced hyperechoic large bowel wall (figure 1A). Native CT imaging was performed (figure 1B). The patient subsequently underwent emergency laparotomy.



Figure 1 
(A) …
Extrahepatic biliary obstruction after percutaneous tumour ablation for hepatocellular carcinoma: aetiology and successful treatment with endoscopic papillary balloon dilatation
Authors: N Sasahira
Journal: Gut (2005)

<b>Background and aims:</b> Percutaneous tumour ablation (PTA), such as ethanol injection and radiofrequency ablation, is now recognised as a primary treatment for hepatocellular carcinoma (HCC). Although PTA is a relatively safe procedure, it can cause biliary obstruction as a rare complication. As patients with cirrhosis undergoing surgery or endoscopic retrograde cholangiopancreatography/sphincterotomy have a high mortality rate from bleeding, we adopted the use of endoscopic papillary balloon dilatation (EPBD) in these patients and now report the results. We retrospectively analysed the incidence of biliary obstruction after PTA and the efficacy of treatment with EPBD. <b>Patients and methods:</b> A total of 1043 patients with HCC were treated by PTA, of whom 538 were treated with transarterial embolisation with up to eight years of follow up. <b>Results:</b> There were 17 (1.6%) cases of hilar obstruction due to tumour progression and 35 (3.4%) cases of extrahepatic obstruction. Apart from the expected causes of biliary obstruction (haemobilia n = 11, gallstones n = 11, and three miscellaneous causes), we found that 10 patients had obstruction due to biliary casts. This is the first description of biliary casts after percutaneous tumour ablation therapy. Extrahepatic biliary obstruction by procedure related haemobilia occurred within three days of PTA while other causes occurred between 0 and 17 (average 4.9) months. Biliary casts occurred more frequently after ethanol injection than after radiofrequency ablation. EPBD successfully dissipated biliary obstruction in 33 of 35 cases, while two died due to hepatic failure despite successful drainage. <b>Conclusions:</b> Extrahepatic biliary obstruction is an uncommon complication after PTA for HCC, and can be safely and effectively treated with EPBD, despite impaired liver function.