tbuckley/cabot-search huggingface dataset:
Akt-Dependent Proapoptotic Effects of Dietary Restriction on Late-Stage Management of a Phosphatase and Tensin Homologue/Tuberous Sclerosis Complex 2–Deficient Mouse Astrocytoma
Authors: Jeremy Marsh, Purna Mukherjee, Thomas N. Seyfried
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Malignant astrocytomas exhibit constitutive Akt phosphorylation due to reduced phosphatase and tensin homologue (PTEN) tumor suppressor expression or to increased growth factor receptor tyrosine kinase activation. Many astrocytomas are also tuberous sclerosis complex 2 (TSC2) protein deficient and exhibit constitutive mammalian target of rapamycin (mTOR) activity. Astrocytomas harboring PTEN/Akt/TSC2 pathway mutations are dependent on glycolysis to satisfy their bioenergetic requirements. Therapies that disrupt energy homeostasis can potentially manage astrocytoma growth and progression. Although dietary restriction (DR) reduces glycolysis and manages early-stage astrocytoma growth, no prior studies have identified the mechanisms involved or determined if DR can also manage late-stage tumor growth. Experimental Design: The effects of a late-onset intermittent DR feeding paradigm were examined in adult C57BL/6J mice bearing the syngeneic CT-2A malignant astrocytoma grown orthotopically or subcutaneously. Results: In contrast to contralateral normal brain, CT-2A was PTEN/TSC2 protein deficient; exhibited constitutive Akt, mTOR, and BAD phosphorylation; and overexpressed insulin-like growth factor-I (IGF-I), IGF-I receptor, hypoxia-inducible transcription factor-1α (HIF-1α), type 1 glucose transporter protein (GLUT1), and pyruvate kinase. DR initiated 10 to 14 days after tumor implantation (late onset) reduced CT-2A growth, delayed malignant progression, and significantly extended survival. DR suppressed phosphorylation of Akt and BAD while reducing expression of IGF-I, HIF-1α, and GLUT1. DR also enhanced procaspase-9/procaspase-3 cleavage but had no effect mTOR phosphorylation. Conclusions: Our findings indicate that IGF-I/Akt signaling is associated with the antiapoptotic and glycolytic phenotype of the CT-2A astrocytoma and that DR targets this pathway. Moreover, PTEN/TSC2 deficiency may impair adaptation to the DR-induced disruption of energy homeostasis, thus enhancing apoptosis. Our findings highlight the efficacy of late-onset DR in managing astrocytoma growth and suggest that DR may be an effective broad-spectrum inhibitor of Akt signaling in PTEN/TSC2–deficient astrocytomas.
Nitric Oxide and Hemodialysis-Induced Hypotension
Authors: Mark A. Perazella
Journal: Annals of Internal Medicine (1996)

Letters15 February 1996Nitric Oxide and Hemodialysis-Induced HypotensionMark A. Perazella, MDMark A. Perazella, MDYale University School of Medicine; New Haven, CT 06510Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-4-199602150-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Yokokawa and colleagues [1] provide interesting data suggesting that increased nitric oxide production may contribute to the development of hemodialysis-induced hypotension. The authors speculate that individual patient sensitivity to heparin, an agent shown to promote nitric oxide production in cultured human vascular endothelial cells [2], may explain the increased production of nitric oxide seen in hypotensive patients, despite the administration of equal amounts of heparin. The mechanism by which increased nitric oxide production occurs, however, remains largely unknown.Another complication of uremia—disordered hemostasis—is also thought to be related in part to platelet dysfunction associated with elevated nitric ...References1. Yokokawa K, Mankus R, Saklayen MG, Kohno M, Yasunari K, Minami M, et al. Increased nitric oxide production in patients with hypotension during hemodialysis. Ann Intern Med. 1995; 123:35-7. Google Scholar2. Yokokawa K, Tahara H, Kohno M, Mandal AK, Yanagiasawa M, Takeda T. Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells. J Clin Invest. 1993; 92:2080-5. Google Scholar3. Remuzzi G, Perico N, Zoja C, Corna D, Macconi D, Vigano G. Role of endothelium-derived nitric oxide in the bleeding tendency of uremia. J Clin Invest. 1990; 86:1768-71. Google Scholar4. Noris M, Benigni A, Boccardo P, Aiello S, Gaspari F, Todeschini M, et al. Enhanced nitric oxide synthesis in uremia: implications for platelet dysfunction and dialysis hypotension. Kidney Int. 1993; 44:445-50. Google Scholar5. Luscher TF, Bock HA, Yang Z, Diederich D. Endothelium-derived relaxing and contracting factors: perspectives in nephrology. Kidney Int. 1991; 39:575-90. Google Scholar Author, Article, and Disclosure InformationAuthors: Mark A. Perazella, MDAffiliations: Yale University School of Medicine; New Haven, CT 06510 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 February 1996Volume 124, Issue 4Page: 454KeywordsErythropoietinHematocritHemeHemorrhageHeparinHypotensionIron deficiencyMedical dialysisNitric oxidePlatelets ePublished: 15 August 2000 Issue Published: 15 February 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract P4-16-03: Effect of doxorubicin and paclitaxel on adipose-derived stem cells and breast cancer cells: Can we incorporate chemotherapy into our reconstructive strategies?
Authors: W Tsuji, CW Chung, MM McLaughlin, JE Valentin, KG Marra, JP Rubin
Journal: Cancer Research (2013)

Abstract Introduction: Breast surgery often results in physical deformities that significantly diminish patient's quality of life. A natural and aesthetically pleasing breast reconstruction can be achieved through autologous fat grafting and the success of this technique has largely been attributed to the regenerative properties of adipose-derived stem cells (ASCs) within fat graft. However, in the setting of resected breast cancer, the growth stimulating and angiogenic effects of ASCs pose a risk of increasing local recurrence rates. Although the safety of autologous fat grafting in the breast cancer population has yet to be determined, potential recurrence risk may be minimized through incorporating tumor-suppressing elements in the graft. This study aimed to determine if doxorubicin and paclitaxel could be used to inhibit breast cancer cells while maintaining the viability and functionality of ASCs in vitro. Materials and methods: Human ASCs were isolated from non-diabetic female patients between 35 and 60 years of age (n = 3). BT-474 and MDA-MB-231 were obtained from ATCC. ASCs, ASCs undergoing adipogenic differentiation, and breast cancer cells were each exposed to a range of doxorubicin-HCl (0, 10, 30, 100, 300, 1000, 3000, or 10000nM) or paclitaxel (0, 0.1, 0.3, 1, 3, 10, 30, 100, or 300nM) concentrations. Proliferation, viability, and differentiation capacity were assessed with commercially available CyQuant, MTT, and AdipoRed assay kits, respectively. Results: Dose-dependent inhibition was observed for doxorubicin in ASCs and both breast cancer cell lines. The IC50 of doxorubicin on ASCs, BT-474, and MDA-MB-231 were 901.3, 656.5, and 333 nM, respectively. Dose-dependent inhibition for paclitaxel was only observed in BT-474 and MDA-MB-231 cells, with IC50 values of 1.809 and 3.477 nM, respectively. ASCs maintained greater than 80% viability over the range of paclitaxel concentrations tested and consequently and IC50 value could not be determined. ASCs differentiation into mature adipocytes was not inhibited by doxorubicin exposure. Discussion: In vitro cytotoxicity studies demonstrated greater doxorubicin and paclitaxel sensitivity in BT-474 and MDA-MB-231 than in ASCs. Furthermore, the presence of doxorubicin did not inhibit ASC differentiation into mature adipocytes. These findings suggest that incorporating chemotherapeutic drugs in fat grafts for breast reconstruction following primary breast cancer surgery may be a viable option for decreasing the risk of cancer recurrence. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-16-03.
Letter: safer cigarettes.
Authors: C M Fletcher, K Ball
Journal: BMJ (1975)

tumour, and this was significantly different (X2 with Yates's correction = 11-18, P<0001) from histopathologically reactive pa,tients.Though it is too soon to assess our results in terms of patients' survival, we would like to suggest that histopa,thological analysis of tumour and lymph nodes might provide an alternative when skin testing is not feasible.-We are, etc.,
Hemodynamic Aspects of Diffuse Myocardial Fibrosis
Authors: EUGENE D. ROBIN, C. SIDNEY BURWELL
Journal: Circulation (1957)

The circulatory changes associated with diffuse myocardial fibrosis have been studied in 11 patients. The characteristics of this form of congestive failure and its similarities to those manifested by constrictive pericarditis and endocardial fibroelastosis are discussed.
Microbiological Examinations and In-Vitro Testing of Different Antibiotics in Therapeutic Endoscopy of the Biliary System
Authors: R. Lorenz, M. Herrmann, A. M. Kassem, N. Lehn, H. Neuhaus, M. Classen
Journal: Endoscopy (1998)

Background and Study Aims: Prior to endoscopic therapeutic procedures, no antibiotic prophylaxis is administered routinely. Because of the reported incidence of infectious complications, which may reach up to 10 %, a prospective study was undertaken to investigate the effects of a prophylactic dose of cefuroxime on the incidence of bacteremia and clinical signs of infection, but no significant effects could be demonstrated. In addition to this published work, blood and bile cultures obtained in this trial were also investigated, and the in-vitro susceptibility to several antibiotics was tested in order to recommend the appropriate substances.
Reevaluation of specificity of Crithidia luciliae kinetoplast as a substrate for detecting antibodies to double-stranded deoxyribonucleic acid
Authors: Samuel E. Steinmetz, Jau-Shyong Deng, Robert L. Rubin, Richard D. Sontheimer, James N. Gilliam
Journal: Journal of the American Academy of Dermatology (1984)
From the physical to the psychological: Mundane experiences influence social judgment and interpersonal behavior
Authors: John A. Bargh, Lawrence E. Williams, Julie Y. Huang, Hyunjin Song, Joshua M. Ackerman
Journal: Behavioral and Brain Sciences (2010)

Abstract Mere physical experiences of warmth, distance, hardness, and roughness are found to activate the more abstract psychological concepts that are analogically related to them, such as interpersonal warmth and emotional distance , thereby influencing social judgments and interpersonal behavior without the individual's awareness. These findings further support the principle of neural reuse in the development and operation of higher mental processes.
Postmenopausal Estrogen Therapy and Cardiovascular Disease
Authors: D B MacLean, A Bostom
Journal: New England Journal of Medicine (1992)

Abstract Background. The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. Our 1985 report in the Journal, based on four years of follow-up, suggested that estrogen therapy reduced the risk of coronary heart disease, but a report published simultaneously from the Framingham Study suggested that the risk was increased. In addition, studies of the effect of estrogens on stroke have yielded conflicting results. Methods. We followed 48,470 postmenopausal women, 30 to 63 years old, who were participants in the Nurses' Health Study and who did not have a history of cancer or cardiovascular disease at base line. During up to 10 years of follow-up (337,854 person-years), we documented 224 strokes, 405 cases of major coronary disease (nonfatal myocardial infarctions or deaths from coronary causes), and 1263 deaths from all causes. Results. After adjustment for age and other risk factors, the overall relative risk of major coronary disease in women currently taki...
Water Metabolism after Cardiac Operations Involving a Gibbon-Type Pump-Oxygenator
Authors: GEORGE S. STURTZ, JOHN W. KIRKLIN, EDMUND C. BURKE, MARSCHELLE H. POWER
Journal: Circulation (1957)

Daily water metabolism of 21 patients was studied for 3 days after intracardiac surgery and whole-body perfusion. The average obligatory water losses of these patients were approximately 500, 750, and 750 ml. per M. 2 of body surface per day on the first, second, and third postoperative day, respectively. A simple system, which combines knowledge of the estimated postoperative water requirement with the known daily change in body weight, was devised to manage accurately water metabolism after intracardiac surgery.
Biting the iron bullet: Endoplasmic reticulum stress adds the pain of hepcidin to chronic liver disease
Authors: Donald J. Messner, Kris V. Kowdley
Journal: Hepatology (2010)

Abstract Hepcidin is a peptide hormone that is secreted by the liver and controls body iron homeostasis. Hepcidin overproduction causes anemia of inflammation, whereas its deficiency leads to hemochromatosis. Inflammation and iron are known extracellular stimuli for hepcidin expression. We found that endoplasmic reticulum (ER) stress also induces hepcidin expression and causes hypoferremia and spleen iron sequestration in mice. CREBH (cyclic AMP response element-binding protein H), an ER stress-activated transcription factor, binds to and transactivates the hepcidin promoter. Hepcidin induction in response to exogenously administered toxins or accumulation of unfolded protein in the ER is defective in CREBH knockout mice, indicating a role for CREBH in ER stress-regulated hepcidin expression. The regulation of hepcidin by ER stress links the intracellular response involved in protein quality control to innate immunity and iron homeostasis.
Deficiency of volume-regulated ClC-3 chloride channel attenuates cerebrovascular remodelling in DOCA-salt hypertension
Authors: Ling-Yun Zheng, Lei Li, Ming-Ming Ma, Yun Liu, Guan-Lei Wang, Yong-Bo Tang, Jia-Guo Zhou, Xiao-Fei Lv, Yan-Hua Du, Yong-Yuan Guan
Journal: Cardiovascular Research (2013)

We have previously demonstrated that ClC-3 chloride channel activity and expression are significantly increased in remodelled cerebral vessels of hypertensive rats. This study aims to examine whether this channel directly regulates cerebrovascular remodelling during hypertension by using ClC-3−/− mice. After DOCA-salt treatment, medial cross-sectional area, media thickness, and media–lumen ratio of the basilar artery of ClC-3+/+ mice were significantly increased, accompanied by reduced lumen diameter, indicating apparent vascular remodelling. The vascular ultrastructure of ClC-3+/+ hypertensive mice by electron microscopy revealed obvious disarray of SMCs and extracellular matrix accumulation. Immunofluorescence analysis showed that fibronectin was overexpressed in ClC-3+/+ DOCA-salt mice. All of these vascular structure alterations were prevented in ClC-3−/− mice despite DOCA-salt treatment. However, propranolol, which reduced blood pressure as effectively as ClC-3 deficiency, failed to prevent basilar artery from remodelling. The vascular structure injury in ClC-3+/+ hypertensive mice was accompanied by significantly increased expression of matrix metalloproteinase (MMP)-2, membrane-type (MT)1-MMP, and tissue inhibitor of metalloproteinase (TIMP)-2, which was inhibited by ClC-3 knockout. Additionally, the increase in transforming growth factor (TGF)-β1 level in serum, as well as phosphorylation of Smad3 at serine 423/425 in basilar artery, induced by DOCA-salt, was markedly prevented in ClC-3−/− mice. Our findings suggest that ClC-3 deficiency attenuates cerebrovascular remodelling possibly via the suppression of MMPs/TIMP expression and TGF-β1/Smad3 signalling pathway in this hypertension.
VAGINAL EXPLORATORY PUNCTURE AND CELIOTOMYTHEIR ADVISABILITY IN DOUBTFUL DIAGNOSIS IN DISEASES OF THE FEMALE GENITAL ORGANS; REPORT OF CASES.
Authors: C. O. THIENHAUS
Journal: JAMA (1903)

When some time ago in a discussion on the differential diagnosis of appendicitis, pyosalpinx, extra-uterine pregnancy, tuberculosis of the right tube and exudates in the right iliac region, I heard the opinion expressed by a teacher of gynecology : "What is the use of going into minute details of differential diagnosis in such cases? The abdomen has to be opened anyhow," I was unwillingly reminded of the general who without sufficient reconnoitering led his troops into an unknown valley, and afterward, encountering insurmountable difficulties, met terrific defeat. Though without question the advancements of modern surgery in the last twenty-five years have made an exploratory laparotomy a relatively safe procedure, so far as the immediate and probably the remote safety of the patient is concerned, yet it must not be forgotten that all therapeutic actions ought in every medical as well as surgical case to be based on a strict and
VAGINAL FIXATION IN RETRODEVIATIONS OF THE UTERUS, WITH SOME REMARKS ON VAGINAL CELIOTOMY.
Authors: X. O. WERDER
Journal: JAMA (1895)

The newest addition to our operative treatment of the backward displacements of the uterus is vaginal fixation. It is the result of a gradual evolution of Schücking's method, and its modifications by Zweifel and Sänger, and has been developed to its present form by Dührssen and Mackenrodt, each of whom claim priority, and is known by their respective names, their methods varying very little from each other. The technique of Dührssen's operation, which is the simpler of the two is as follows: the cervix, having been seized by a volsellum forceps, is drawn down toward the vulva; a transverse incision is made through the anterior vaginal wall close to its attachment to the cervix, care being taken to avoid the bladder. The latter is then dissected away from the uterus just the same as in vaginal hysterectomy. It is important to push the vesico-uterine fold as far up toward the
Sézary syndrome in an 11-year-old girl
Authors: Lynn Meister, Ana M. Duarte, Joanna Davis, Jorge L. Perez, Lawrence A. Schachner
Journal: Journal of the American Academy of Dermatology (1993)

All forms of cutaneous T-cell lymphoma are rare in children. We describe an 11-year-old girl who had generalized exfoliative erythroderma, intense pruritus, peripheral lymphadenopathy, mycosis cells in the skin and lymph nodes, and Sézary cells in the peripheral blood. Results of a biopsy specimen of involved skin showed changes consistent with mycosis fungoides. A classic case of Sézary syndrome has not previously been reported in childhood or preadolescence. All forms of cutaneous T-cell lymphoma are rare in children. We describe an 11-year-old girl who had generalized exfoliative erythroderma, intense pruritus, peripheral lymphadenopathy, mycosis cells in the skin and lymph nodes, and Sézary cells in the peripheral blood. Results of a biopsy specimen of involved skin showed changes consistent with mycosis fungoides. A classic case of Sézary syndrome has not previously been reported in childhood or preadolescence.
Measurement of Sputum <i>Mycobacterium tuberculosis</i> Messenger RNA as a Surrogate for Response to Chemotherapy
Authors: LUCY E. DESJARDIN, MARK D. PERKINS, KATHY WOLSKI, SHIRLEY HAUN, LUCILÉIA TEIXEIRA, YING CHEN, JOHN L. JOHNSON, JERROLD J. ELLNER, REYNALDO DIETZE, JOSEPH BATES, M. DONALD CAVE, KATHLEEN D. EISENACH
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Effective treatment regimens for pulmonary tuberculosis are difficult to assess because of the slow growth rate of Mycobacterium tuberculosis in culture and its protracted clearance from sputum. A rapid method that reflects effective antimicrobial activity would markedly advance evaluation of treatment and promote the assessment of new antituberculosis drugs. Conventional methods measure the progressive reduction of numbers of acid-fast bacilli in the sputum smear and the clearance of organisms in sputum culture. In this study, we measured levels of M. tuberculosis 85B (alpha antigen) messenger RNA (mRNA), 16S ribosomal RNA (rRNA), and IS6110 DNA in patients' sputa to ascertain whether they could serve as potential surrogate markers of response to chemotherapy. Sputum specimens were sequentially collected for up to a year from 19 smear-positive pulmonary tuberculosis patients receiving an optimal drug treatment regimen. Nucleic acids were isolated from these specimens, and two M. tuberculosis molecular targets (mRNA, DNA) were quantified, using the ABI Prism 7700 Sequence Detection System. The Mycobacterium genus-specific 16S rRNA was quantified with a limiting dilution RT-PCR assay. Results show that levels of 85B mRNA declined after initiation of therapy, as did viable M. tuberculosis colony counts, with 90% of patients becoming negative for both markers after 2 mo of treatment. The rapid disappearance of M. tuberculosis mRNA from sputum suggests that it is a good indicator of microbial viability and a useful marker for rapid assessment of response to chemotherapy.
Absence of ligands bound to glycoprotein IIB-IIIA on the exposed surface of a thrombus may limit thrombus growth in flowing blood.
Authors: H F Heynen, M Lozano Molero, P G de Groot, H K Nieuwenhuis, J J Sixma
Journal: Journal of Clinical Investigation (1994)

We examined the distribution of glycoprotein IIb-IIIa (GPIIb-IIIa) and its ligands fibrinogen and von Willebrand factor (vWf) on platelets which had adhered under flow conditions. Immunoelectron microscopy was performed on whole mounts and frozen thin sections of adhering platelets. GPIIb-IIIa was homogeneously distributed on dendritic platelets and on interplatelet membranes of formed thrombi. Fibrinogen and vWf were predominantly associated with interplatelet membranes and membranes facing the substrate. On whole mounts, vWf appeared in clumps and linear arrays, representing the tangled or extended forms of the multimeric molecule. From semiquantitative analysis, it appeared that fibrinogen and vWf were, respectively, nine- and fourfold higher on interplatelet membranes than on surface membranes facing the blood stream, while GPIIb-IIIa was evenly distributed over all platelet plasma membranes. Ligand-induced binding sites (LIBS) of GPIIb-IIIa, as measured with conformation specific monoclonal antibodies RUU 2.41 and LIBS-1, were present on the surface of adhered platelets and thrombi. A redistribution of LIBS-positive forms of GPIIb-IIIa towards interplatelet membranes was not observed. Our data support the hypothesis that, under flow conditions, ligands have first bound to activated GPIIb-IIIa but this binding is reversed on the upper surface of adhering platelets. This relative absence of ligands on the exposed surface of thrombi may play a role in limiting their size.