tbuckley/cabot-search huggingface dataset:
Orthostatic Hypotension in Diabetic Patients
Authors: Samuel Vaisrub
Journal: JAMA (1975)

How odd that a giraffe with its heart-to-head distance exceeding 2 meters does not find it difficult to maintain circulatory homeostasis in the upright position, whereas man with a mere 30 cm separating the two organs sometimes does. Physiologists have come closer to explaining the giraffe's circulatory agility 1 than the homeostatic sluggishness of humans with orthostatic hypotension.  Failure to regulate blood pressure on assuming the upright position may be idiopathic or secondary to a known neurologic or systemic disease. It is much more common among diabetic patients than in the general population.  The increased prevalence of orthostatic hypotension in diabetics need not be too surprising. Autonomic neuropathy could well compromise baroreceptor reflexes in the carotid sinuses and aortic arch and chemoceptor reflexes in the carotid and aortic bodies. The plausibility of such a mechanism is supported by the frequency of associated peripheral neuropathy in these patients.  Plausibility, however, does
Effect of bedtime ranitidine on overnight gastric acid output and intragastric pH: dose/response study and comparison with cimetidine.
Authors: J B Chambers, D Pryce, J M Bland, T C Northfield
Journal: Gut (1987)

A dose/response study has been carried out in seven patients with endoscopically proven duodenal ulcers in symptomatic remission, measuring intragastric pH and gastric acid output overnight after a bedtime dose of ranitidine (75 mg, 150 mg, and 300 mg); and the results have been compared with placebo and with bedtime cimetidine 400 mg. The currently recommended ranitidine maintenance dose (150 mg) was the optimum because it was significantly more effective than ranitidine 75 mg in terms of intragastric pH but not of acid output, and there was no difference from 300 mg in terms of either measurement. It was also significantly more effective than the currently recommended cimetidine maintenance dose (400 mg) in terms of inhibiting overnight acid output (92% vs 80% inhibition, p less than 0.05), and of maintaining intragastric pH above 5 (100% vs 17% of the overnight period, p less than 0.001).
Lipopolysaccharide from Escherichia coli reduces antigen-induced bronchoconstriction in actively sensitized guinea pigs.
Authors: E Vannier, J Lefort, A Lellouch-Tubiana, B Terlain, B B Vargaftig
Journal: Journal of Clinical Investigation (1991)

Bronchoconstriction (BC) is the main feature of anaphylaxis in the guinea pig. Since LPS induces lung inflammation and antigen-induced BC depends on the endogenous formation of histamine and arachidonate metabolites, we studied whether LPS might modulate antigen-induced BC. Guinea pigs were sensitized subcutaneously with 10 micrograms ovalbumin (OA) on days 0 and 14. LPS (100 micrograms/kg) was injected intravenously on day 21, and daily injections of LPS were continued before the antigenic challenge on day 22, 23, 24, or 25. Intratracheal injection of 100 micrograms OA induced an abrupt and reversible BC. Single or repetitive injections of LPS reduced BC. LPS is likely to reduce the OA-induced BC by affecting the histamine-dependent component of BC, since (a) LPS induced a partial degranulation of lung mast cells; (b) BC is reduced by mepyramine, an histamine receptor antagonist; (c) LPS did not affect BC in mepyramine-treated guinea pigs; (d) LPS reduced histamine release by OA-stimulated guinea pig lungs in vitro. Moreover, the in vitro OA-induced production of arachidonate metabolites was also reduced by LPS. The decreased formation of TXB2 was not only secondary to a reduced release of histamine, since LPS inhibited TXB2 formation in the presence of mepyramine. Finally, the FMLP-induced BC and mediator release were inhibited by LPS, whereas the platelet activating factor-induced pulmonary responses were not. Thus, the protective effect of LPS is not antigen-specific and does not result from a general desensitization. These studies indicate that a single dose of LPS reduces the antigen-induced BC by reducing histamine release from lung mast cells, although a decreased formation of eicosanoids may contribute to the protective effect of LPS.
Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy
Authors: Amar Gajjar, Stefan M. Pfister, Michael D. Taylor, Richard J. Gilbertson
Journal: Clinical Cancer Research (2014)

Abstract High-throughput genomic technologies have shed light on the biologic heterogeneity of several pediatric brain tumors. The biology of the four common pediatric brain tumors—namely medulloblastoma; ependymoma; high-grade glioma (HGG), including diffuse intrinsic pontine glioma; and low-grade glioma—is highlighted in this CCR Focus article. The discovery that medulloblastoma consists of four different subgroups, namely WNT, SHH, Group 3, and Group 4, each with distinct clinical and molecular features, has affected the treatment of children with medulloblastoma. Prospective studies have documented the efficacy of SMO inhibitors in a subgroup of patients with SHH medulloblastoma. Efforts are ongoing to develop specific therapies for each of the subgroups of medulloblastoma. Similar efforts are being pursued for ependymoma, HGG, and diffuse intrinsic pontine glioma where the disease outcome for the latter two tumors has not changed over the past three decades despite several prospective clinical trials. Developing and testing targeted therapies based on this new understanding remains a major challenge to the pediatric neuro-oncology community. The focus of this review is to summarize the rapidly evolving understanding of the common pediatric brain tumors based on genome-wide analysis. These novel insights will add impetus to translating these laboratory-based discoveries to newer therapies for children diagnosed with these tumors. See all articles in this CCR Focus section, “Discoveries, Challenges, and Progress in Primary Brain Tumors.” Clin Cancer Res; 20(22); 5630–40. ©2014 AACR.
Trypanosoma cruzi trans-sialidase: enhancement of virulence in a murine model of Chagas' disease.
Authors: M Chuenkova, M E Pereira
Journal: The Journal of Experimental Medicine (1995)

Trypanosoma cruzi, the etiological agent of Chagas' disease, expresses a trans-sialidase at highest levels in infective trypomastigotes, where it attaches to the plasma membrane by a glycophosphoinositol linkage. Bound enzyme sheds into the extracellular milieu in a soluble form. Experiments performed in vitro suggest that the trans-sialidase participates in several parameters of T. cruzi-host interactions, like cell adhesion and complement resistance. However, the role that membrane-bound and soluble trans-sialidase plays in the infection of mammals is not understood. To begin to study the role the enzyme may play in vivo, T. cruzi trypomastigotes were inoculated subcutaneously into mice that had been sensitized for various times with the purified protein. A single dose of either endogenous or recombinant trans-sialidase injected into the connective tissues of BALB/c mice greatly enhanced parasitemia and mortality. Maximum enhancement was achieved with 1-2-h priming. Injection of the enzyme after the parasites had been established in the inoculation site had little, if any, consequence in modifying virulence. The enhancement did not seem to be through a direct effect of the enzyme on trypomastigote-host cell interactions because it occurred when the sites of trans-sialidase sensitization and parasite inoculation were physically separate. Rather, virulence enhancement seemed to depend on inflammatory cells, since priming with trans-sialidase had no significant effect in severe combined immunodeficiency mice, which lack functional T and B lymphocytes. However, antibody response to T. cruzi in the trans-sialidase-primed BALB/c mice was the same as in the control animals. Virulence enhancement was specific for the trans-sialidase because it did not occur in mice primed with Newcastle virus sialidase, which has the same substrate specificity as the T. cruzi enzyme, or with the sialidase from the bacterium Vibrio cholerae, whose substrate specificity is broader than the trypanosome sialidase. Furthermore, no enhancement of virulence occurred after sensitization with another adhesion protein (penetrin) purified from T. cruzi trypomastigotes and engineered bacteria, nor with bacterial lipopolysaccharide. The virulence-promoting activity of soluble trans-sialidase in the mouse model may be physiologically relevant because it was achieved with tiny doses, approximately 1-2 microgram/kg, raising the possibility that neutralization of the enzyme with specific probes could impair the development of Chagas' disease. In fact, a monoclonal antibody specific for the tandem repeat in the trans-sialidase COOH terminus enhanced infection of BALB/c mice, in agreement with earlier experiments in vitro, whereas antibodies against an amino acid sequence in the Cys region had the opposite effect.
Abstract 3955: The tumor suppressor C/EBPdelta promotes hypoxia-induced EMT and expression of stem cell markers through inhibition of FBXW7: Implications for mammary tumor metastasis.
Authors: Balamurugan Kuppusamy, Esta Sterneck
Journal: Cancer Research (2013)

Abstract The transcription factor CCAAT/enhancer binding protein delta (C/EBPδ) exhibits tumor-suppressor like-qualities such as downregulation of cyclin D1, and promotion of growth arrest and apoptosis. However, using a mouse model of mammary tumorigenesis (MMTV-Neu), we had found that C/EBPδ has dual functions. C/EBPδ suppresses primary tumor incidence while also augmenting metastatic progression. The pro-metastatic function of C/EBPδ can be correlated with a role in hypoxia adaptation and expression of pro-inflammatory genes and macrophage activation. C/EBPδ exerts both of these functions through inhibition of FBXW7, a component of SCF E3 ubiquitin ligase complex, which targets substrates such as c-myc and Notch for degradation (Balamurugan et al, 2010; Balamurugan et al., under revision). Hypoxia is believed to promote tumor progression in part by inducing epithelial-mesenchymal transition (EMT), which contributes to the generation of stem-like cancer cells (CSCs). In the present study, we found that hypoxia-induced EMT and expression of CSCs markers were compromised in Cebpd null primary tumor cells and in human breast tumor cells when C/EBPδ expression was silenced. On the other hand, silencing of the C/EBPδ-repressed gene FBXW7 was sufficient to induce a mesenchymal-like phenotype. Loss of FBXW7 has been shown to promote acquisition of stemness. In line with this notion, we found that overexpression of FBXW7 in the breast tumor cell line MDA-MB-468 reduced expression of aldehyde dehydrogenase 1 (Aldh1), C/EBPδ and the active form of NOTCH (NICD). Together, these data suggest that C/EBPδ augments - whereas its target FBXW7 prevents - EMT and breast cancer stem cell development, which may be an additional mechanism by which C/EBPδ promotes metastatic progression. Our current investigations are aimed at understanding how the different functions of C/EBPδ are integrated depending on cellular environment and context that results in its tumor promoting function despite its tumor suppressor role. Citation Format: Balamurugan Kuppusamy, Esta Sterneck. The tumor suppressor C/EBPdelta promotes hypoxia-induced EMT and expression of stem cell markers through inhibition of FBXW7: Implications for mammary tumor metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3955. doi:10.1158/1538-7445.AM2013-3955
When and How to Treat Essential Thrombocythemia
Authors: Tiziano Barbui, Guido Finazzi
Journal: New England Journal of Medicine (2005)

Essential thrombocythemia is one of the chronic myeloproliferative disorders, a heterogeneous group of diseases involving clonal hematopoietic stem cells that also includes polycythemia vera, idiopathic myelofibrosis, and chronic myelogenous leukemia.1 Among these disorders, essential thrombocythemia has the most favorable outcome: patients with this disease have a life span that nearly rivals that of a healthy population matched by age and sex.2 The principal causes of death in patients with essential thrombocythemia are thrombosis, hemorrhage, and progression to myelofibrosis or acute myelogenous leukemia. The myelosuppressive therapy that prevents vascular events in essential thrombocythemia may itself increase the risk of transformation to . . .
Deficiency of cannabinoid receptor of type 2 worsens renal functional and structural abnormalities in streptozotocin-induced diabetic mice
Authors: Federica Barutta, Serena Grimaldi, Irene Franco, Stefania Bellini, Roberto Gambino, Silvia Pinach, Alessandro Corbelli, Graziella Bruno, Maria Pia Rastaldi, Teresa Aveta, Emilio Hirsch, Vincenzo Di Marzo, Gabriella Gruden
Journal: Kidney International (2014)
Self-Monitored Blood Glucose: The Essential Biofeedback Signal in the Diabetic Patient's Effort to Achieve Normoglycemia
Authors: Karl Irsigler, Christine Bali-Taubald
Journal: Diabetes Care (1980)

Seventeen pregnant diabetic women participated in a special outpatient program during which they learned to self-monitor blood glucose (BG) and to vary insulin dosage on the basis of the results. The Ames Eyetone reflectance meter and the Boehringer Reflomat were used for BG analysis. BG was self-monitored at least twice a day, with a 24-h profile once a week. The average mean BG from 220 wk of pregnancy was 101 mg/dl. No macrosomia has been seen in deliveries so far. Delivery has been later than is usual in our hospital. The number of necessary days of hospitalization was reduced by 45, as compared with a previous intensive outpatient program for pregnant diabetic women without self-monitoring. An important element of the program was a weekly group session in which individual experiences were shared and discussed in detail. Patients were enthusiastic about the program.
Differentiation of restrictive cardiomyopathy from pericardial constriction: Assessment of diastolic function by radionuclide angiography
Authors: Constantine N. Aroney, Terrence D. Ruddy, Humberto Dighero, Michael A. Fifer, Charles A. Boucher, Igor F. Palacios
Journal: Journal of the American College of Cardiology (1989)
Observations on THE TREATMENT OF RODENT ULCERS
Authors: N. S. Finzi
Journal: BMJ (1933)

growth.The resulting scar is, of course, not incons:der-Observations able, and, anyhow, the cosmetic result cannot be compared ON with that following radium treatment.If a rodent is THE TREATMENT OF RODENT ULCERS excised and recurs, its subsequent treatment with radium or x rays is always more difficult and less certa n than BY is the case when it is treated ab initio.Even more so is N. S. FINZI, M.B., D.M.R.E.this true if -recurrences have been excised one or more MIEDICAL OFFICER TO X-RAY DEPARTMElNT, ST.BARTHOLONMEW'S times.Treatment of the scar by radium after an exc:sion ISIIIAL will usually prevent recurrence, but one loses the advan-Rodent ulcer " is the term we use for basal-celled tage of freedom from scarring that one gets from such epithelioma of the appendages of the skin.It is locally radium treatment as is described below.The only malignant, but never, or practically never, spreads to advantage that can be urged for surgery is that one can the lymphatic glands while it still remains a basal-cellel have a microscopical examination of the specimen.At epithelioma.In its later stages, however, whether it the present day this method of treatment has been super- spreads or not, it tends to become a true squamous seded.In the early stages a biopsy often means excision epithelioma, and though even then it shows little of the whole growth, and in a typical case there seems tendency to spread to the lymphatic glands, it does no object in excising a portion, especially as radium occasionally do so.Its commonest site is on the face, treatment is made more difficult thereby.When there especially the inner canthus, the nose, or the cheek, but iS doubt a biopsy may sometimes be advisable, especially it may occur in any part of the body.Usually a single, if epithelioma is suspected.In advanced cases the
The Silent Epidemic — The Health Effects of Illiteracy
Authors: Erin N. Marcus
Journal: New England Journal of Medicine (2006)

He came in for a "tune-up." He was 64 years old, with a "history of noncompliance," according to the resident, and he hadn't taken his diabetes or cardiac medications for weeks. We weren't quite sure why. He was alert, he appeared to be intelligent and interested in getting well, and he was able to get his prescriptions filled at a reduced cost. Before he went home, we explained why he needed to take his medicines and reviewed the frequency and doses with him several times. He told us he would follow up with his doctor (though he couldn't remember the . . .
CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting the p53-dependent signaling pathway
Authors: Qichao Huang, Jibin Li, Jinliang Xing, Weiwei Li, Hongwei Li, Xia Ke, Jing Zhang, Tingting Ren, Yukui Shang, Hushan Yang, Jianli Jiang, Zhinan Chen
Journal: Journal of Hepatology (2014)
An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis
Authors: Patrick M Lynch, Carol A Burke, Robin Phillips, Jeffrey S Morris, Rebecca Slack, Xuemei Wang, Jun Liu, Sherri Patterson, Frank A Sinicrope, Miguel A Rodriguez-Bigas, Elizabeth Half, Steffen Bulow, Andrew Latchford, Sue Clark, William A Ross, Bonnie Malone, Hennie Hasson, Ellen Richmond, Ernest Hawk
Journal: Gut (2015)

Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any.The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria.112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was -13.0% for CXB+DFMO and -1.0% for CXB (p=0.69). Mean % change in adenoma burden was -40% (CXB+DFMO) vs -27% (CXB) (p=0.13). Video-based global polyp change was -0.80 for CXB+DFMO vs -0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02).CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves.ClinicalTrials.gov number N01-CN95040.
Relationship of fluorescence polarization to cell lineage in lymphocytes from normal subjects and patients with chronic lymphocytic leukemia
Authors: Taya V. Glotzer, Leonard F. Liebes, Denise Kanganis, Robert Silber
Journal: American Journal of Hematology (1987)

Previous investigations have shown differences in fluorescence polarization between normal and chronic lymphocytic leukemia lymphocytes following incubation with the probe 1,6-diphenyl-1,3,5-hexatriene. In the present study, we determined the fluorescence polarization of unseparated or enriched subpopulations of T and B lymphocytes from normal subjects and patients with chronic lymphocytic leukemia. As had been observed by others, the mean polarization (P) value at 25 degrees C for unseparated chronic lymphocytic leukemia lymphocytes, .240 +/- .007 (N = 22), was lower than that of unseparated normal lymphocytes, .248 +/- .005 (N = 18), P less than .001 (Student's t-test). The difference was greater when B-enriched populations were compared. The mean P value of B-cell-enriched chronic lymphocytic leukemia lymphocytes, .240 +/- .007 (N = 5), was significantly lower than that of B-cell-enriched normal preparations, .256 +/- .004 (N = 5), P less than .001. In contrast, no significant difference was found between normal and chronic lymphocytic leukemia T cells. The anomalous fluorescence polarization manifested by chronic lymphocytic leukemia lymphocytes of B-cell origin serves to distinguish this lineage from its normal counterpart and from T cells of either source.
An Evaluation of 123I-Iodonzomycinarabinoside (IAZA) as a Marker of Tissue Hypoxia in Patients with Diabetes Mellitus
Authors: A. Al Arafaj, E. A. Ryan, K. Hutchison, J. Mercer, L. I. Weibe, A. J.B. McEwan
Journal: Clinical Nuclear Medicine (1994)

Arafaj, A. Al1; Ryan, E. A.2; Hutchison, K.1; Mercer, J.1; Weibe, L. I.1; McEwan, A. J.B.3 Author Information