tbuckley/cabot-search huggingface dataset:
In Situ Akt Phosphorylation in the Nucleus Tractus Solitarii Is Involved in Central Control of Blood Pressure and Heart Rate
Authors: Hsiao-Ning Huang, Pei-Jung Lu, Wan-Chen Lo, Chia-Hui Lin, Michael Hsiao, Ching-Jiunn Tseng
Journal: Circulation (2004)

Previously, we have shown that nitric oxide (NO) plays a significant role in central cardiovascular regulation and modulates the baroreflex in the nucleus tractus solitarii (NTS) of rats. NO production is mediated by activation of NO synthase (NOS). Insulin signaling was involved in controlling peripheral blood pressure via the activation of endothelial NOS. Here, we investigated whether the insulin signal transduction pathway is involved in controlling central cardiovascular effects.Insulin was injected into NTS of urethane-anesthetized male Wistar-Kyoto (WKY) rats. Unilateral microinjection (60 nL) of insulin (100 IU/mL) into the NTS produced prominent depressor and bradycardic effects in 8- and 16-week-old WKY rats. In addition, pretreatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the NOS inhibitor L-NAME into the NTS caused attenuation of the cardiovascular response evoked by insulin in either 8- or 16-week-old WKY rats. Western blot analysis showed a significant increase (2.6+/-0.4-fold; P<0.05) in Akt phosphorylation after insulin injection, whereas LY294002 abolished the insulin-induced effects. In situ Akt phosphorylation was found in NTS by immunohistochemistry analysis after injection of insulin. This in situ Akt phosphorylation was abolished significantly after injection of LY294002.Take together, these results suggest that the insulin-PI3K-Akt-NOS signaling pathway may play a significant role in central cardiovascular regulation.
Flow cytometric analysis of DNA synthetic phase fraction of the normal appearing colonic mucosa in patients with colorectal neoplasms.
Authors: S Nakamura, J Goto, Y Kitayama, J P Sheffield, I C Talbot
Journal: Gut (1995)

DNA synthetic (S) phase fractions of normal appearing colonic mucosa in Japanese and British patients with colorectal neoplasms were compared with those in patients without colonic neoplasms. Normal crypts were isolated from fresh surgical specimens of the large intestine by the use of EDTA. After fixation with 70% ethanol, isolated crypts were digested with pepsin into single nuclei suspensions. These were stained with propidium iodide and examined by flow cytometry. S phase fraction was calculated from the flow cytometry DNA histogram using Baisch's method. S phase fractions of normal appearing crypts in Japanese and British patients with colorectal tumours were not significantly different and analysed together. S phase fraction of normal appearing colonic crypts in 14 patients with familial adenomatous polyposis (FAP) was 10.23 (2.59%) (mean SD)) ranging from 5.8 to 18.8. S phase fraction of background normal mucosal in patients with large adenomas (over 2 cm) and adenocarcinomas were 9.74 (3.76%) (range, 2.7-16.1) and 8.93 (3.54%) (range, 2.9-18.9) respectively. In normal mucosa of patients without any colorectal neoplasms, S phase fraction was 8.99 (3.94)% (range, 3.9-17.7). There was no statistically significant difference in S phase fractions of normal mucosa in the four groups. Our results show that an increase in proliferative activity of background colonic crypts is not necessary for tumour development.
Lung Natural Killer Cells Play a Major Counter-Regulatory Role in Pulmonary Vascular Hyperpermeability After Myocardial Infarction
Authors: Xiaoxiang Yan, Ahmed E. Hegab, Jin Endo, Atsushi Anzai, Tomohiro Matsuhashi, Yoshinori Katsumata, Kentaro Ito, Tsunehisa Yamamoto, Tomoko Betsuyaku, Ken Shinmura, Weifeng Shen, Eric Vivier, Keiichi Fukuda, Motoaki Sano
Journal: Circulation Research (2013)

Natural killer (NK) cells are lymphocytes of the innate immune system that play specialized and niche-specific roles in distinct organs.We investigated the possible function of NK cells in the pathogenesis of congestive heart failure after myocardial infarction.Depletion of NK cells from mice had little effect on cytokine expression (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β), neutrophil and macrophage infiltration into infarcted myocardium, or left ventricular remodeling after myocardial infarction. However, these mice exhibited severe respiratory distress associated with protein-rich, high-permeability alveolar edema accompanied by neutrophil infiltration. In addition, there were 20-fold more NK cells in the mouse lungs than in heart, and these cells were accumulated around the vasculature. CD107a-positive and interferon-γ-positive cell populations were unchanged, whereas IL-10-positive populations increased. Adoptive transfer of NK cells from wild-type mice, but not from IL-10 knockout mice, into the NK cell-depleted mice rescued the respiratory phenotype. IL-1β-mediated dextran leakage from a lung endothelial cell monolayer was also blocked by coculture with NK cells from wild-type mice but not from IL-10 knockout mice.This study is the first to identify a critical role for lung NK cells in protecting lung from the development of cardiogenic pulmonary edema after myocardial infarction.
Abstract 3576: Lapatinib in combination with doxorubicin is highly damaging to cardiac myocytes
Authors: Brian B. Hasinoff, Daywin Patel, Xing Wu
Journal: Cancer Research (2011)

Abstract Lapatinib (Tykerb) is dual tyrosine kinase inhibitor targeting the HER2 (ERBB2) and EGFR (ERBB1, HER1) pathways. It is used to treat ER+/EGFR+/HER2+ breast cancer patients and patients who have HER2-positive advanced breast cancer that has progressed after previous treatment with other chemotherapeutic agents. Lapatinib, which was initially rated as having no cardiotoxicity, has recently been shown in a clinical trial to produce low levels of cardiotoxicity that is reversible. Using a neonatal rat cardiac myocyte model we have investigated the ability of lapatinib alone and in combination with doxorubicin to damage myocytes. Lapatinib alone at pharmacological concentrations did not significantly cause myocyte damage. However, doxorubicin-induced myocyte damage was greatly increased by the addition of low nanomolar lapatinib concentrations. Previous clinical studies have shown that the combination of trastuzumab (Herceptin) and doxorubicin was highly cardiotoxic. Because trastuzumab also targets HER2 receptors, the lapatinib/doxorubicin combination provides a good model to probe the mechanism of this cardiotoxicity using a rat myocyte model. Lapatinib treatment alone had little or no effect on myocyte mitochondrial membrane potential, on oxidation of intracellular DCF (dichlorofluorescein), on intracellular ATP levels or on caspase 3/7 induction. The doxorubicin cardioprotective agent dexrazoxane was able to greatly reduce doxorubicin-induced myocyte damage. However, dexrazoxane was not able to reduce the increase in myocyte damage produced by adding lapatinib to the doxorubicin treatment. The effect of lapatinib on the change in phosphorylation of ACC (acetyl-coenzyme A carboxylase), which is a measure of a change in cellular energy status, was also determined. Doxorubicin-induced growth inhibitory effects on K562 cells, which contain very low levels of ERBB1/2 protein, were not affected by the addition of lapatinib. This result suggests that inhibition of ERBB1/2 is required for the synergistic toxic effects seen with doxorubicin in myocytes. In conclusion these results suggest that combination therapy employing doxorubicin and lapatinib may produce increased cardiotoxicity. Support: CIHR and a Canada Research Chair in Drug Development to BBH. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3576. doi:10.1158/1538-7445.AM2011-3576
Reversal of low-molecular-weight heparin-induced bleeding in patients with pre-existing hypercoagulable states with human recombinant activated factor VII concentrate
Authors: Kashif Firozvi, Ruby Anne E. Deveras, Craig M. Kessler
Journal: American Journal of Hematology (2006)

Low-molecular-weight heparins are widely employed in prophylactic and therapeutic antithrombotic regimens for venous thromboembolic events. Excessive anticoagulation with low-molecular-weight heparins rarely can precipitate catastrophic bleeding complications. Currently, there is no specific or reliable antidote that can reverse the anticoagulant effects of low-molecular-weight heparins efficiently and safely. This report describes three individuals with underlying hypercoagulable states, who developed clinically significant bleeding complications while receiving therapeutic anticoagulation with enoxaparin. All of the hemorrhagic events subsequently were safely and effectively reversed with a single intravenous bolus infusion of recombinant activated factor VIIa (RFVIIa) concentrate. Hemoglobins, prothrombin times, and clinical overt bleeding were monitored before and after the administration of RFVIIa. In all three cases, bleeding was controlled without an increase in thrombotic events. Our findings demonstrate that RFVIIa can rapidly and safely reverse the hemorrhagic adverse effects associated with excessive levels of low-molecular-weight heparin in patients with pre-existing hypercoagulable conditions and/or acute venous thromboembolism. Am. J. Hematol. 81:582–589, 2006. © 2006 Wiley-Liss, Inc.
Metronidazole and Indian kala-azar: results of a clinical trial.
Authors: M Mishra, B D Thakur, M Choudhary
Journal: BMJ (1985)

to progressive renal failure.Plasma phosphate and serum uric acid concentrations and blood pressure, however, were always within the normal range, and a renal biopsy specimen showed no evidence of interstitial nephritis and only minimal arteriolar hyalinisation.In the rat extensive renal ablation is followed by increases in glomerular capillary hydraulic pressure, glomerular capillary plasma flow rate, and single nephron glomerular filtration rate, and these changes may eventually cause glomerulosclerosis.3Similar processes may have occurred in this case.Children maintain stable renal function for up to 33 years after unilateral nephrectomy.4Our patient had lost a large proportion of his renal substance 19 years before he developed renal failure, suggesting that the eventual development of glomerulosclerosis in human remnant kidneys depends on both the number of remaining nephrons and the interval since injury.I Chanutin A, Ferris ED.Experimental renal insufficiency produced by partial nephrectomy.1.Control diet.
Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels.
Authors: P L Golden, T J Maccagnan, W M Pardridge
Journal: Journal of Clinical Investigation (1997)

The peripheral production of leptin by adipose tissue and its putative effect as a signal of satiety in the central nervous system suggest that leptin gains access to the regions of the brain regulating energy balance by crossing the brain capillary endothelium, which constitutes the blood-brain barrier in vivo. The present experiments characterize the binding and internalization of mouse recombinant leptin in isolated human brain capillaries, an in vitro model of the human blood-brain barrier. Incubation of 125I-leptin with isolated human brain capillaries resulted in temperature-dependent binding: at 37 degrees C, approximately 65% of radiolabeled leptin was bound per milligram of capillary protein. Two-thirds of the bound radioactivity was resistant to removal by acid wash, demonstrating endocytosis of 125I-leptin into capillary cells. At 4 degrees C, binding to isolated capillaries was reduced to approximately 23%/mg of protein, the majority of which was acid wash resistant. Binding of 125I-leptin to brain capillary endothelial plasma membranes was saturable, described by a two-site binding model with a high-affinity dissociation constant of 5.1+/-2.8 nM and maximal binding capacity of 0.34+/-0.16 pmol/mg of membrane protein. Addition of porcine insulin or insulin-like growth factor at a final concentration of 100 nM had a negligible effect on leptin binding. These results provide evidence for a leptin receptor that mediates saturable, specific, temperature-dependent binding and endocytosis of leptin at the human blood-brain barrier.
Cardiac repair achieved by bone marrow mesenchymal stem cells/silk fibroin/hyaluronic acid patches in a rat of myocardial infarction model
Authors: Nai-Hsin Chi, Ming-Chia Yang, Tze-Wen Chung, Jia-Yu Chen, Nai-Kuan Chou, Shoei-Shen Wang
Journal: Biomaterials (2012)
Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts.
Authors: S Harada, J A Nagy, K A Sullivan, K A Thomas, N Endo, G A Rodan, S B Rodan
Journal: Journal of Clinical Investigation (1994)

PGE1 and PGE2 are potent stimulators of bone formation. Osteogenesis is strongly dependent on angiogenesis. Vascular endothelial growth factor (VEFG), a secreted endothelial cell-specific mitogen, has been implicated in physiological and pathological angiogenesis. The aim of this study was to examine the possible role of VEGF in PG stimulation of bone formation. We found that in rat calvaria-derived osteoblast-enriched cells and in the osteoblastic RCT-3 cell line PGE2 and E1 increased VEGF mRNA and protein levels. The increased expression of VEGF mRNA produced by PGE2 was rapid (maximal at 1 h), transient (declined by 3 h), potentiated by cycloheximide, and abolished by actinomycin D. PGE2 had no effect on VEGF mRNA stability, suggesting transcriptional regulation of VEGF expression by PGF2. Rp-cAMP, a cAMP antagonist, suppressed VEGF mRNA induced by PGE2, indicating cAMP mediation. The upregulation of VEGF expression by PGE2 in the preosteoblastic RCT-1 cells was potentiated by treatment with retinoic acid, which induces the differentiation of these cells. The upregulation of VEGF mRNA by PGE2 was inhibited by dexamethasone treatment. In addition, Northern blot analysis showed that VEGF mRNA is expressed in adult rat tibia. In summary, we documented, for the first time, the expression of VEGF in osteoblasts and in bone tissue. Stimulation of VEGF expression by PGs and its suppression by glucocorticoids, which, respectively, stimulate and suppress bone formation, strongly implicate the involvement of VEGF in bone metabolism.
A NOTE ON THE PRODUCTION OF ACID BY PNEUMOCOCCI
Authors: Glenn E. Cullen, Alan M. Chesney
Journal: The Journal of Experimental Medicine (1918)

1. Actively growing pneumococci produce acid at such a rate that change in the pH of the medium parallels change in rate of growth. 2. The death of the pneumococci is not followed by change in the reaction. 3. Acidification during growth in beef infusion media proceeds until a pH of about 7 is reached. At this point growth stops. The increase in hydrogen ion concentration is not the only origin of the injury to the cell that causes lag in a subsequent culture. 4. The increase in hydrogen ion concentration of the medium is not the sole cause of cessation of growth.
Prospective double-blind trial of synthetic steroid (Org OD 14) for preventing postmenopausal osteoporosis.
Authors: R Lindsay, D M Hart, A Kraszewski
Journal: BMJ (1980)

A double-blind trial of Org OD 14, a synthetic steroid with an unusual endocrine profile, was conducted on 100 postmenopausal women; of these, 63 completed two years9 treatment (33 Org OD 14; 30 placebo). A dose of 2.5 mg/day successfully prevented bone loss over two years, whereas a significant reduction in bone mineral content occurred in women taking placebo, the rate being comparable to that in earlier studies (p less than 0.01). At the dosage used (2.5 mg/day) Org OD 14 also significantly reduced the severity of menopausal complaints (flushing, sweating, etc). Vabra aspiration curettage in 20 cases 6-18 months after starting active treatment showed no evidence of endometrial hyperplasia, though weak proliferation of the endometrium was seen in three. Org OD 14 may provide a new approach to hormonal prevention of bone loss in postmenopausal women without inducing appreciable endometrial stimulation; the potential value of Org OD 14 in osteoporosis and other post-climacteric complaints warrants further investigation.
Testing the anterior pituitary: hypoglycaemia produced by continuous intravenous insulin infusion.
Authors: G H Newman, I A Macdonald, S P Allison
Journal: BMJ (1983)

The response of growth hormone, cortisol, and catecholamines to hypoglycaemia produced by a continuous intravenous infusion of insulin was investigated in 10 normal subjects and 15 patients with pituitary disease. The insulin infusion rate was started at 2 U/hour for adolescents, 4 U/hour for adults, and 6 U/hour for patients with acromegaly. If required the rate was increased during the test depending on changes in blood glucose, measured by a Reflomat with low reading glucose oxidase strips. Stopping the infusion when the blood glucose concentration had fallen to 2.0 mmol/l (36 mg/100 ml) resulted in a maximum further fall of 0.7 mmol/l (13 mg/100 ml) and a subsequent spontaneous rise in blood glucose concentration. The rise was identical in normal subjects and in patients with hypopituitarism, further evidence that pituitary hormones--in contrast to glucagon and catecholamines--are relatively unimportant in the recovery from hypoglycaemia. The only patient who required intravenous glucose to restore normoglycaemia was a patient with longstanding insulin dependent diabetes. A comparison with the conventional bolus injection test showed that continuous intravenous insulin infusion was more reliable in producing adequate but not excessive hypoglycaemia and the hormone responses were equivalent. The continuous intravenous insulin infusion may offer particular advantages in the investigation of growth hormone deficiency.
European Union prepares to tackle counterfeit drugs
Authors: R. Watson
Journal: BMJ (2010)

In the wild-type brain, the <i>Drosophila</i> classic cadherin DE-cadherin is expressed globally by postembryonic neuroblasts and their lineages (“secondary lineages”), as well as glial cells. To address the role of DE-cadherin in the larval brain, we took advantage of the dominant-negative DE-cad<sup>ex</sup>construct, the expression of which was directed to neurons, glial cells, or both. Global expression of DE-cad<sup>ex</sup> driven by a heat pulse during the early second instar resulted in a severe phenotype that included deficits in neural proliferation. Neuroblasts appeared in approximately normal numbers but had highly reduced mitotic activity. When the DE-cad<sup>ex</sup> construct was driven by the glial-specific driver gcm-Gal4, the effect of DE-cad<sup>ex</sup> on neuroblast proliferation could be replicated, which indicates that DE-cadherin acts in glial cells to promote proliferation of neuroblasts. Expression of DE-cad<sup>ex</sup> in neurons, cortex glia, or both results in abnormalities in cortex layering and in trajectories of secondary axons. In the wild-type brain, neuroblasts and neurons generated at different time points are arranged concentrically around the neuropile, with the DE-cadherin-positive neuroblasts and young secondary neurons at the surface, followed by older secondary neurons and primary neurons. Axons of secondary lineages follow a straight radial course toward the neuropile. Processes of glial cells located in the cortex form a scaffold, called trophospongium, that enwraps neuroblasts and neurons. Expression of DE-cad<sup>ex</sup> in neurons, cortex glia, or both disrupted the regular placement of neuroblasts and secondary neurons and resulted in abnormal trajectories of cell body fiber tracts. We conclude that DE-cadherin plays a pivotal role in larval brain proliferation, brain cortex morphogenesis, and axon growth.
Skin manifestations associated with tumours of the brain
Authors: V.C. ANDREEV, I. PETKOV
Journal: British Journal of Dermatology (1975)

In a 4-year period seventy-seven patients with tumours of the brain were investigated for skin manifestations. These were observed in twenty-four (31-2%) and fall into three main groups: Pruritus. Thirteen patients complained of pruritus. Most characteristic is the pruritus of the nostrils, which was observed in six patients. It can be extremely severe and is a sign of an advanced tumour. Pigmentary disorders were observed in seven patients. In two, vitiligo appeared simultaneously with the brain tumour symptoms. In the others, hyperpigmentation appeared on the face later in the course of the disease. Hyperkeratotic changes were manifest in four patients. Two had a mild hyperkeratosis of the palms and soles. The other two developed in addition an ichthyosiform atrophy of the skin. The possible pathogenesis of the skin manifestations associated with brain tumours is discussed.
Marihuana
Authors: Harold Kolansky
Journal: JAMA (1975)

"MARIHUANA! Can it hurt you?" was a question asked with some urgency by a boy in a group of ninth-grade students visiting the US Capitol Building. The youngsters, curious about a group of men walking by, were told that they were scientists who just completed a day of testimony on the toxicity of marihuana to a subcommittee of the Committee on the Judiciary in the US Senate. This boy's compelling question highlights an important issue in medicine today. We possess accumulated scientific knowledge of marihuana's toxic effects on humans, yet we are without adequate and effective means to deliverthis information to the public. The consequence is that the known toxic effects from marihuana use are not adequately prevented. Wynder and Peacock<sup>1</sup>said recently that modern medicine has been highly successful in the prevention of devastating infectious diseases, through the coordinated efforts of researchers and clinicians. They indicate that in certain
Hemodynamically Mediated Acute Renal Failure
Authors: Franklin H. Epstein, Bryan D. Myers, S. Mark Moran
Journal: New England Journal of Medicine (1986)

Classic (Oliguric) Acute Renal FailureThe syndrome of acute renal failure was first recognized during World War II. The sudden but ultimately reversible depression of renal function observed initially in victims of crush injuries,1 and later in association with prolonged hypotension from various causes,2 , 3 was characterized as having an initial oliguric phase, which was followed in one to two weeks by a diuretic phase that heralded the onset of recovery. During the subsequent four decades, an extensive literature devoted to acute renal failure has provided an accurate description of the clinical, laboratory, and histopathological features of this injury. Only in . . .
AMA Guidelines for Adolescent Preventive Services (GAPS): Recommendations and Rationale
Authors: Elizabeth M. Alderman
Journal: JAMA (1994)

The Guidelines for Adolescent Preventive Services (GAPS) were developed by the American Medical Association's Department of Adolescent Health and a national scientific advisory board. GAPS represents the first recommendations for adolescent health delivery and preventive services designed on a national level.<i>AMA Guidelines for Adolescent Preventive Services (GAPS): Recommendations and Rationale</i>, provides the practitioner with in-depth examination of the information used to develop the guidelines and reviews GAPS in a clear and concise manner. GAPS consists of 24 recommendations addressing 14 health topics that are outlined in the volume's introduction. For each health topic, recommendations for health guidance, screening, or immunizations are presented. These recommendations are organized in an excellent table comparing GAPS and traditional medical care. Each specific GAPS recommendation is listed in the next section of the introduction. The remainder of the book is devoted to describing the specific scientific research supporting each GAPS recommendation within each of