tbuckley/cabot-search huggingface dataset:
Anxiolytic Activity of Atrial Natriuretic Peptide in Patients With Panic Disorder
Authors: Andreas Ströhle, Michael Kellner, Florian Holsboer, Klaus Wiedemann
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Preclinical evidence exists for the anxiolytic activity of atrial natriuretic peptide, which is released during lactate-induced panic attacks. Atrial natriuretic peptide receptor modulation may have antipanic activity in patients with panic disorder. METHOD: The effects of 150 μg of atrial natriuretic peptide and placebo on panic attacks induced by cholecystokinin tetrapeptide (CCK-4) (25 μg) were studied in 10 panic disorder patients. The panicogenic activity of CCK-4 was measured with the Acute Panic Inventory. RESULTS: Panic attacks occurred in seven patients in the placebo condition and in two patients in the atrial natriuretic peptide condition. CCK-4 administration was accompanied by a significant increase in Acute Panic Inventory scores. Pretreatment with atrial natriuretic peptide resulted in significantly lower Acute Panic Inventory scores than pretreatment with placebo. CONCLUSIONS: The results support the antipanic activity of atrial natriuretic peptide. Nonpeptidergic atrial natriuretic peptide receptor ligands may be ultimately used to treat anxiety disorders.
Localization of cardiac myosin-specific antibody in myocardial infarction.
Authors: B A Khaw, G A Beller, E Haber, T W Smith
Journal: Journal of Clinical Investigation (1976)

Specific localization of purified antibody against cardiac myosin has been demonstrated in areas of altered myocardial membrane permeability after experimental myocardial infarction. Intravenously administered radioiodine-labeled antimyosin was selectively localized in infarcted myocardium of seven dogs 24 h after coronary occlusion. The mean ratio (+/-SE) of antimyosin antibody in infarcted to normal myocardium in the center of the infarct was 4.2+/-0.4 for endocardial and 2.9+/-0.3 for epicardial layers. By utilizing (Fab')2 fragments of antimyosin obtained by pepsin digestion of purified antibody, the ratio of uptake was increased in eight dogs to 6.1+/-0.6 in the endocardial and 3.3+/-0.4 in the epicardial layers at the infarct center 24 h after occlusion. These ratios were further increased in the infarct center to 13.8+/-1.2 in the endocardial and 7.3+/-0.8 in the epicardial layers when eight dogs were sacrificed 72 h after coronary occlusion. The specificity of antimyosin (Fab')2 localization in infarcted myocardium was demonstrated in four dogs by simultaneous intravenous administration of 125I-labeled antimyosin (Fab')2 and 131I-labeled normal rabbit gamma globulin (Fab')2. Nonspecific trapping of normal rabbit IgG (Fab')2 was observed to be about 38% of total antimyosin (Fab')2 uptake in the central zone of infarction. Regional blood flow was related to antimyosin (Fab')2 uptake in infarcted myocardium by utilizing simultaneous administration of 85Sr-labeled microspheres. An inverse exponential relationship between antimyosin (Fab')2 uptake and regional blood flow was observed (r=0.85). The specific localization of antimyosin antibody or its (Fab')2 components in infarcted myocardium suggests a conceptually new approach to myocardial infarct localization and sizing.
Bestrophin-3 (Vitelliform Macular Dystrophy 2–Like 3 Protein) Is Essential for the cGMP-Dependent Calcium-Activated Chloride Conductance in Vascular Smooth Muscle Cells
Authors: Vladimir V. Matchkov, Per Larsen, Elena V. Bouzinova, Aleksandra Rojek, Donna M. Briggs Boedtkjer, Veronika Golubinskaya, Finn Skou Pedersen, Christian Aalkjær, Holger Nilsson
Journal: Circulation Research (2008)

Although the biophysical fingerprints (ion selectivity, voltage-dependence, kinetics, etc) of Ca(2+)-activated Cl(-) currents are well established, their molecular identity is still controversial. Several molecular candidates have been suggested; however, none of them has been fully accepted. We have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells. This novel current has been shown to coexist with a "classic" (cGMP-independent) Ca(2+)-activated Cl(-) current and to have characteristics distinct from those previously known for Ca(2+)-activated Cl(-) currents. Here, we suggest that a bestrophin, a product of the Best gene family, is responsible for the cGMP-dependent Ca(2+)-activated Cl(-) current based on similarities between the membrane currents produced by heterologous expressions of bestrophins and the cGMP-dependent Ca(2+)-activated Cl(-) current. This is supported by similarities in the distribution pattern of the cGMP-dependent Ca(2+)-activated Cl(-) current and bestrophin-3 (the product of Best-3 gene) expression in different smooth muscle. Furthermore, downregulation of Best-3 gene expression with small interfering RNA both in cultured cells and in vascular smooth muscle cells in vivo was associated with a significant reduction of the cGMP-dependent Ca(2+)-activated Cl(-) current, whereas the magnitude of the classic Ca(2+)-activated Cl(-) current was not affected. The majority of previous suggestions that bestrophins are a new Cl(-) channel family were based on heterologous expression in cell culture studies. Our present results demonstrate that at least 1 family member, bestrophin-3, is essential for a well-defined endogenous Ca(2+)-activated Cl(-) current in smooth muscles in the intact vascular wall.
A PROSPECTIVE STUDY OF COGNITIVE PERFORMANCE IN IRRITABLE BOWEL SYNDROME: VISUOSPATIAL MEMORY DEFICITS AS A STABLE FEATURE
Authors: P J Kennedy, G Clarke, A P Allen, Ann O'Neill, J A Groeger, E M M Quigley, F Shanahan, J F Cryan, T G Dinan
Journal: Gut (2013)

<h3>Introduction</h3> The cognitive neurobiological model of IBS (Kennedy <i>et al</i>., 2012), a disorder of the brain-gut axis, proposes that key pathophysiological features, such as altered hypothalamic-pituitary-adrenal (HPA) axis function, or heightened immune activity, may lead to impaired cognitive performance. Recently IBS patients were found to exhibit visuospatial memory deficits (Kennedy <i>et al</i>., 2013). However, a prospective assessment is essential to confirm if cognitive dysfunction is a stable feature of IBS. <h3>Aims/Background</h3> To prospectively assess visuospatial memory performance in IBS, in comparison to disease controls Crohn9s diesase (CD] and healthy controls (HC). <h3>Method</h3> At baseline (Visit 1) and 6 months (Visit 2), IBS patients (baseline n=39; age (M): 28 yrs; IQ:105.5), matched CD patients (baseline n=18;age (M):32 yrs; IQ:103.4), and matched HC (baseline n=40;age (M):28 yrs; IQ:108.5), were assessed using a selection of cognitive tests from the CANTAB and Stroop test. Abdominal pain severity at time of testing was reported by IBS patients on a scale ranging from 0–100. <h3>Results</h3> At Visit 1 &amp; 2, IBS patients displayed visuospatial memory deficits [Paired Associates Learning (PAL) test]; greater errors at the 6 pattern stage (baseline: p&lt;0.05), which also approached significance across Visit 1 &amp; 2 (p=0.05); greater number of trials needed to complete the PAL Visit 1 &amp; 2 (p&lt;0.05). Pain severity did not correlate with PAL performance (p&gt;0.05). <h3>Conclusion</h3> Visuospatial memory dysfunction is a stable feature of IBS. These results may inform future management of this debilitating disorder in which there is a great unmet medical need.
Free erythrocyte protoporphyrin level and nerve conduction velocity in end-stage renal disease.
Authors: G M London, Y Nordmann, M E Safar, S Metral, P Milliez
Journal: BMJ (1975)

Increased free erythrocyte protoporphyrin concentrations and depressed motor nerve conduction velocities (MNCV) were observed in 45 patients on maintenance haemodialysis. Neither of these findings could be correlated with age, duration or frequency of dialysis, or the degree of uraemia present. A strong negative correlation (r=--0-53; P less than 0-001), however, existed between the free erythrocyte protoporphyrin level and the MNCV, which suggested either (a) a direct effect of iron status on nerve function, or (b) a toxic factor in "uraemia" that depresses both nerve conduction and haemsynthetase activity.
Electrocardiographic QRS Axis Shift as a Manifestation of Hyperkalemia
Authors: Gordon A. Ewy
Journal: JAMA (1971)

Four patients had deviation of the mean QRS axis as an electrocardiographic manifestation of hyperkalemia. Two patients had a leftward and superior axis shift and two had a rightward and inferior axis shift. These findings are reported so that the spectrum of electrocardiographic changes associated with hyperkalemia will be appreciated.
AN IRRIGATING STAND.
Authors: WALTER E. M. RANCHOUS
Journal: JAMA (1903)

The accompanying illustration shows an irrigating stand of use to the venereal specialist and also to the general practitioner who has much to do with the irrigating treatment of gonorrhea in the male. It will enable the physician to get conveniently near his patient and irrigate without soiling the clothes of either party, since there is no splashing of the returning fluid other than that which is the receiving basin will accommodate.
Critical periods for chlorpyrifos-induced developmental neurotoxicity: alterations in adenylyl cyclase signaling in adult rat brain regions after gestational or neonatal exposure.
Authors: Armando Meyer, Frederic J Seidler, Justin E Aldridge, Charlotte A Tate, Mandy M Cousins, Theodore A Slotkin
Journal: Environmental Health Perspectives (2003)

Developmental exposure to chlorpyrifos (CPF) alters the function of a wide variety of neural systems. In the present study we evaluated the effects in adulthood of CPF exposure of rats during different developmental windows, using the adenylyl cyclase (AC) signaling cascade, which mediates the cellular responses to numerous neurotransmitters. Animals were exposed on gestational days (GD) 9-12 or 17-20 or on postnatal days (PN) 1-4 or 11-14 and assessed at PN60. In addition to basal AC activity, we evaluated the responses to direct AC stimulants (forskolin, Mn2+) and to isoproterenol, which activates signaling through ss-adrenoceptors coupled to stimulatory G-proteins. CPF exposure in any of the four periods elicited significant changes in AC signaling in a wide variety of brain regions in adulthood. In general, GD9-12 was the least sensitive stage, requiring doses above the threshold for impaired maternal weight gain, whereas effects were obtained at subtoxic doses for all other regimens. Most of the effects were heterologous, involving signaling elements downstream from the receptors, and thus shared by multiple stimulants; superimposed on this basic pattern, there were also selective alterations in receptor-mediated responses, in G-protein function, and in AC expression and subtypes. Exposures conducted at GD17-20 and later all produced sex-selective alterations. These results suggest that developmental exposure to CPF elicits long-lasting alterations in cell-signaling cascades that are shared by multiple neurotransmitter and hormonal inputs; the resultant abnormalities of synaptic communication are thus likely to occur in widespread neural circuits and their corresponding behaviors.
TUBERCULOSIS IN THE MIDDLE STATES AND ITS CURABILITY.
Authors: JOHN A. ROBISON
Journal: JAMA (1901)

When asked to present a paper on this subject I consented willingly, but it was willingness born of ignorance; I had no idea of the task before me. On investigating the literature on the subject of tuberculosis in the Middle States, I found that the mass of information concerning the climatology of these states and the factors which might cause or cure consumption was very meager. The subject soon outran the bounds of a twenty-minute paper. Therefore, I have arbitrarily selected the following states for consideration: Michigan, Ohio, Indiana, Illinois, Kentucky, Wisconsin, Minnesota, Iowa, Missouri, North and South Dakota, Nebraska, and Kansas. They lie between the Appalachian system of mountains on the east and the Rocky mountains on the west, the Mississippi river draining the valley which slopes toward its shores. The altitude of this valley varies from 400 to the highest mountain tops of 3000 feet. But the greater
STATE MEDICINE TO THE PRESENT TIME.
Authors: FRANKLIN STAPLES
Journal: JAMA (1897)

State Medicine, the department of science and government pertaining to public sanitation and public health, is a development of modern times, is largely a product of the civilization of the latter half of the present century; yet in its rapid extension it has become nearly universal, has an important place in the state enactments of nearly all nations. Physicians were recognized by law in very early times, and were provided for in the armies and at the courts of kings. In the Middle Ages something was known of medical jurisprudence. Legal medicine is said to have been founded by one Paolo Zachias of Rome, at the beginning of the seventeenth century. What is mentioned as state medicine, taught in the German universities in the eighteenth century, was but the forensic medicine of the times relating to laws in medical jurisprudence. The establishment of state medicine in all countries follows much
The Antitumor and Antiangiogenic Activity of Vascular Endothelial Growth Factor Receptor Inhibition Is Potentiated by ErbB1 Blockade
Authors: Patrizia Sini, Lorenza Wyder, Christian Schnell, Terence O'Reilly, Amanda Littlewood, Ralph Brandt, Nancy E. Hynes, Jeanette Wood
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Receptor tyrosine kinases of the ErbB family play important roles in the control of tumor growth. Vascular endothelial growth factor (VEGF) stimulates endothelial cell proliferation, enhances vascular permeability, and plays an important role in tumor vascularization. We evaluated the effects of selective VEGF receptor (VEGFR; PTK787/ZK222584) and ErbB (PKI166 and ZD1839) inhibitors on tumor growth and angiogenesis and asked whether additional therapeutic benefit was conferred by combination treatment. Experimental Design: The antitumor activity of each inhibitor alone or in combination was assessed in human cancer models in immunocompromised mice. ErbB receptor expression and activation of downstream signaling pathway was evaluated in both tumor and endothelial cells. Results: Both ErbB inhibitors significantly enhanced the antitumor activity of PTK787/ZK222584. In vitro, ErbB1 inhibition blocked VEGF release by tumor cells and proliferation of both tumor and endothelial cells. In an in vitro angiogenesis assay, epidermal growth factor (EGF) stimulated the release of VEGF by smooth muscle cells resulting in increased angiogenesis, a response blocked by administration of PTK787/ZK222584. Under basal condition, both ZD1839 and PTK787/ZK222584 blocked sprouting, likely via inhibition of an autocrine ErbB1 loop and VEGFR signaling, respectively, in endothelial cells. In conditions of limiting VEGF, EGF plays an important role in endothelial cell proliferation, survival, and sprouting. Conclusion: We have shown that activation of ErbB1 triggers a plethora of effects, including direct effects on tumor and endothelial cells and indirect effects mediated via induction of VEGF release. Simultaneous blockade of ErbB1 and VEGFR pathways results in a cooperative antitumor effect, indicating that this combination may represent a valid therapeutic strategy.
Liver Disease and Aspergillosis
Authors: Basil Varkey
Journal: JAMA (1983)

<h3>To the Editor.—</h3> In a recent CASE REPORT, D'Silva et al (1982;248:1495) describe disseminated aspergillosis occurring in a patient who was presumably immunocompetent. This patient had a history of excessive alcohol intake, icterus on admission, increased prothrombin time, and elevated liver enzyme levels. Autopsy findings did not reveal features of cirrhosis or alcoholic hepatitis; focal abscesses in the liver containing hyphae of<i>Aspergillus</i>were seen. On the basis of these findings, the authors surmise that the<i>Aspergillus</i>microabscesses probably accounted for the altered liver function study results. Autopsy findings also showed a moderate degree of fatty metamorphosis and areas of centrilobular congestion and necrosis unrelated to the<i>Aspergillus</i>abscesses. In view of these findings, an alternate possibility— that liver injury predisposed to asperillosis—certainly exists. Further support for this possibility is found in the literature. A review of the literature revealed four cases of disseminated aspergillosis occurring in patients with liver
SELECTIVE TRIGGERING OF HUMAN T AND B LYMPHOCYTES IN VITRO BY POLYCLONAL MITOGENS
Authors: Melvyn Greaves, George Janossy, Michael Doenhoff
Journal: The Journal of Experimental Medicine (1974)

Human lymphocytes from spleen and tonsils have been cultured with a variety of polyclonal mitogens. Cultures consisted of either unseparated T and B cells or alternatively purified T or B lymphocytes. The purity of the starting cell populations and the origin of activated lymphoblasts was analyzed with a panel of seven markers which discriminate between T and B cells. The selectivity of the lymphocyte responses was influenced by cell populations in a given culture, the mitogen used, and to a limited extent on culture conditions. Purified T lymphocytes from tonsil and spleen responded to phytohemagglutinin (PHA), pokeweed mitogen (PWM), and staphylococcal enterotoxin B (SEB). Purified B cells from spleen responded well to PWM, weakly to SEB and lipopolysaccharide, but not at all to PHA. Tonsil B cells responded weakly to PWM and SEB but not to PHA. Some B lymphocytes do respond to PHA in the presence of activated T cells. These results are discussed in relation to previously reported selective responses of human cells and parallel studies in animal species.
Autonomy is important but not as important as the "sanctity of life"
Authors: J. H. Hendriks
Journal: BMJ (1996)

This is a new dilemma for physicians and Mok and Nelson have made an important contribution to the burgeoning publications on the effects on children of traumatic events.

Vietnamese boat people, including children, fasted or were fasted (my emphasis), for up to five days. The authors report selected interventions on 57 children under 15 years of age: the implication is that children were presented for treatment by their parents, as the focus is on parental responsibility. …
Correlating Abdominal Bruits With Angiographic Findings
Authors: M. J. McLoughlin
Journal: JAMA (1975)

<h3>To the Editor.—</h3> In our article correlating abdominal bruits with angiographic findings (232:1238-1242, 1975) we attempted to present the facts, leaving the reader to draw his own conclusions about their clinical significance. This was perhaps unfortunate since your editorial (232:1270-1271, 1975) attributes to us an implication that we certainly do not endorse. Although we stated that "an epigastric bruit cannot usually be ascribed to any other cause, unless celiac stenosis has been excluded by lateral aortography," this does not mean that we advocate aortography in all such patients. On the contrary, we would stress the innocent nature of most epigastric bruits and recommend no further action in the absence of other significant findings. Even in patients with other findings including hypertension, celiac stenosis is still the most likely cause of an epigastric bruit, which should be interpreted with caution. Second, we cannot agree that we implied that bruits are always
RECANALIZATION PATTERN OF PORCINE CORONARY CHRONIC TOTAL OCCLUSIONS.
Authors: Paul Fefer, Beiping Qiang, Nigel Munce, Normand Robert, Kevan J. Anderson, Xui Ling Qiang, Max Weisbrod, Graham A. Wright, Bradley H. Strauss
Journal: Journal of the American College of Cardiology (2010)
Abstract IA1: Keynote Presentation: BRAF and RAS signaling in melanoma from basic to translational and clinical research
Authors: Richard M. Marais
Journal: Clinical Cancer Research (2012)

Abstract BRAF is a protein kinase that is mutated in about half of human melanomas. Its activator, the small G-protein NRAS, is mutated in another 20% of cases. Drugs that inhibit BRAF mediate impressive responses in melanoma patients whose tumors carry mutations in BRAF, but are not effective in patients whose tumors express wild-type BRAF. Unexpectedly however, whereas BRAF drugs inhibit MEK/ERK signaling in melanoma cells that express oncogenic BRAF, they activate MEK/ERK signaling in cells that express oncogenic RAS. This paradoxical activation of MEK/ERK signaling in melanoma cells that express oncogenic RAS occurs because BRAF drugs drive the formation of dimers between BRAF and a closely related family member, called CRAF. These hetero- and homo-dimers contain one partner that is drug-bound and one partner that is drug-free, and the drug-bound partner activates the drug-free partner through a conformational change, or by acting as a scaffold protein. Notably, this paradoxical activation drives the formation of non-melanoma skin lesions (keratoacanthomas, squamous cell carcinomas) in about a third of patients. Using a two-stage skin carcinogenesis model, we find that this is not because BRAF inhibitors are tumor promoters per se; rather they act by accelerating the inevitable in susceptible patients by driving the growth of pre-existing lesions through paradoxical RAF activation. We also find that nilotinib is a weak RAF inhibitor that activates the RAF paradox and thereby drives survival in drug-resistant chronic mylogenous leukemia (CML) cells. Our data show how improved understanding of signaling responses to BRAF inhibitors can lead to improved patient care.
Abstract 4100: Aberrant methylation of the PTPRO gene in peripheral blood as a potential biomarker in esophageal squamous cell carcinoma patients
Authors: Hao Zhang, Yanjie You, Yuping Chen, Xiaoxuan Zheng, Stephen J. Meltzer
Journal: Cancer Research (2012)

Abstract Purpose: Compared with tyrosine kinases, our understanding of protein-tyrosine phosphatases (PTPs) in cancer is limited, and further knowledge could provide new therapeutic targets and diagnostic markers. Inactivation of protein tyrosine phosphatase receptor-type O (PTPRO), a new member of the PTP family, by hypermethylation has been described in several forms of cancers. We evaluated PTPRO hypermethylation as a potential epigenetic biomarker in esophageal squamous cell carcinoma (ESCC). Experimental Design: In 36 primary ESCC tissue specimens and matched peripheral plasma and buffy coat samples, we determined the methylation status of PTPRO by performing methylation-specific PCR. Correlations with PTPRO methylation and clinicopathologic features were also examined. Results: PTPRO hypermethylation was observed in 27 (75%) of 36 primary tumors and correlated significantly with depth of invasion (T-stage, P = 0.013). Among matched peripheral blood samples from ESCC patients, 13 (36.1%) of 36 had detectable methylated PTPRO in plasma, and 15 (41.7%) of 36 had it in the buffy coat. No methylated PTPRO was observed in normal peripheral blood samples from 10 healthy individuals. In addition, promoter methylation correlated with loss of PTPRO mRNA expression, and demethylation by 5-aza-dC treatment led to gene reactivation in PTPRO-methylated and -silenced ESCC cell lines. Conclusions: This is the first report for detection of PTPRO as a non-invasive biomarker for solid tumors in peripheral blood. Our findings suggest that hypermethylated PTPRO occurs frequently in ESCC. Its detection in the peripheral blood of ESCC patients illustrates its potential clinical application as an epigenetic biomarker for noninvasive diagnosis and disease monitoring. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4100. doi:1538-7445.AM2012-4100