tbuckley/cabot-search huggingface dataset:
MicroRNA-133a Protects Against Myocardial Fibrosis and Modulates Electrical Repolarization Without Affecting Hypertrophy in Pressure-Overloaded Adult Hearts
Authors: Scot J. Matkovich, Wei Wang, Yizheng Tu, William H. Eschenbacher, Lisa E. Dorn, Gianluigi Condorelli, Abhinav Diwan, Jeanne M. Nerbonne, Gerald W. Dorn
Journal: Circulation Research (2009)

MicroRNA (miR)-133a regulates cardiac and skeletal muscle differentiation and plays an important role in cardiac development. Because miR-133a levels decrease during reactive cardiac hypertrophy, some have considered that restoring miR-133a levels could suppress hypertrophic remodeling.To prevent the "normal" downregulation of miR-133a induced by an acute hypertrophic stimulus in the adult heart.miR-133a is downregulated in transverse aortic constriction (TAC) and isoproterenol-induced hypertrophy, but not in 2 genetic hypertrophy models. Using MYH6 promoter-directed expression of a miR-133a genomic precursor, increased cardiomyocyte miR-133a had no effect on postnatal cardiac development assessed by measures of structure, function, and mRNA profile. However, increased miR-133a levels increased QT intervals in surface electrocardiographic recordings and action potential durations in isolated ventricular myocytes, with a decrease in the fast component of the transient outward K+ current, I(to,f), at baseline. Transgenic expression of miR-133a prevented TAC-associated miR-133a downregulation and improved myocardial fibrosis and diastolic function without affecting the extent of hypertrophy. I(to,f) downregulation normally observed post-TAC was prevented in miR-133a transgenic mice, although action potential duration and QT intervals did not reflect this benefit. miR-133a transgenic hearts had no significant alterations of basal or post-TAC mRNA expression profiles, although decreased mRNA and protein levels were observed for the I(to,f) auxiliary KChIP2 subunit, which is not a predicted target.These results reveal striking differences between in vitro and in vivo phenotypes of miR expression, and further suggest that mRNA signatures do not reliably predict either direct miR targets or major miR effects.
Ascorbic Acid Blocking of Aminopyrine Nitrosation in NZO/BI Mice2
Authors: Melvin Greenblatt
Journal: JNCI Journal of the National Cancer Institute (1973)

NZO/BI mice were given a single gavage of 17.3 µmoles 4-dimethylaminoantipyrine and 58 µmoles sodium nitrite (NaNO2), a dose that produced acute centrilobular necrosis of the liver in 48 hours, due to dimethylnitrosamine formation. The effect of the addition of ascorbic acid in varying concentrations to the gavage mixture was studied. High concentrations of ascorbic acid (2 times the molar concentration of NaNO2) prevented hepatic necrosis. When the concentration of ascorbic acid was reduced to equimolar with NaNO2, the protective effect was incomplete.
Impaired Autonomic Function Is Associated With Increased Mortality, Especially in Subjects With Diabetes, Hypertension, or a History of Cardiovascular Disease
Authors: Jeanet Gerritsen, Jacqueline M. Dekker, Ben J. TenVoorde, Piet J. Kostense, Robert J. Heine, Lex M. Bouter, Rob M. Heethaar, Coen D.A. Stehouwer
Journal: Diabetes Care (2001)

OBJECTIVE—Measures of baroreflex sensitivity, heart rate variability (HRV), and the classical Ewing test parameters are currently used for the diagnosis of diabetic autonomic neuropathy and for mortality risk stratification after myocardial infarction. However, the strengths of the associations of these measures of autonomic function with risk of mortality have never been compared in one study population. Furthermore, no evidence is available on the possible effect of glucose tolerance on these associations. RESEARCH DESIGN AND METHODS—The study population (n = 605) consisted of a glucose tolerance–stratified sample from a general population (50–75 years of age). Cardiac cycle duration and continuous finger arterial pressure were measured under two conditions: at rest and on metronome breathing. From these readings, seven parameters of autonomic function were assessed (one Ewing, five HRV, and one baroreflex sensitivity). RESULTS—During 9 years of follow-up, 101 individuals died, 43 from cardiovascular causes. Subjects with diabetes and low levels of the autonomic function parameters, indicating impaired autonomic function, had an approximately doubled risk of mortality. This association was consistent, though not statistically significant, for all parameters. The elevated risk was not observed in subjects without diabetes, hypertension, or prevalent cardiovascular disease. CONCLUSIONS—Impaired autonomic function is associated with all-cause and cardiovascular mortality. Moreover, the results of the present study suggest that cardiac autonomic dysfunction in patients already at risk (diabetes, hypertension, or history of cardiovascular disease) may be especially hazardous.
Carcinoma of the Lower Uterine Segment: A Newly Described Association With Lynch Syndrome
Authors: Shannon N. Westin, Robin A. Lacour, Diana L. Urbauer, Rajyalakshmi Luthra, Diane C. Bodurka, Karen H. Lu, Russell R. Broaddus
Journal: Journal of Clinical Oncology (2008)

Endometrial carcinoma in the lower uterine segment (LUS) is a poorly described cancer that can be clinically confused with endocervical carcinoma. We performed a case-comparison study to document the clinicopathologic characteristics of LUS tumors and their association with risk factors for endometrial cancer.The clinical records and pathology reports from women who underwent hysterectomy at our institution for endometrial or endocervical adenocarcinoma over an 11-year interval were reviewed. The LUS group consisted of women with endometrial tumors that clearly originated between the lower uterine corpus and the upper endocervix. Immunohistochemistry and microsatellite instability and MLH1 methylation assays were performed.Thirty-five (3.5%) of 1,009 women had endometrial carcinoma of the LUS. Compared with patients with corpus tumors, LUS patients were younger, had higher stage tumors, and had more invasive tumors. Preoperative diagnosis of the LUS tumors more frequently included the possibility of endocervical adenocarcinoma. Seventy-three percent of the LUS tumors had an immunohistochemical expression pattern typical of conventional endometrioid adenocarcinoma. Ten (29%) of 35 women with LUS tumors were confirmed to have Lynch syndrome or were strongly suspected to have Lynch syndrome on the basis of tissue-based molecular assays.The prevalence of Lynch syndrome in patients with LUS endometrial carcinoma (29%) is much greater than that of the general endometrial cancer patient population (1.8%) or in endometrial cancer patients younger than age 50 years (8% to 9%). On the basis of our results, the possibility of Lynch syndrome should be considered in women with LUS tumors.
SELF-INDUCED PSYCHOSIS WITH HYPERTHYROIDISM COMPLICATING MANIC DEPRESSIVE PSYCHOSIS
Authors: GEORGE N. THOMPSON
Journal: American Journal of Psychiatry (1945)

A patient suffering with manic-depressive psychosis, depressed type, the diagnosis being based upon the history of repeated cyclothymic depressions with typical symptomatology and complete recoveries with remissions free from symptoms, attempted during a depression to commit suicide so that it would be unrecognized as such. Massive, prolonged thyroid overdosage extending over a period of 1½ years resulted in a clinical picture of hyperthyroidism indistinguishable from typical Grave's disease. A marked increase in the overdosage resulted in the clinical picture of psychosis with hyperthyroidism. Removal of the drug resulted in the remission of symptoms due to thyroid toxicity, the clinical picture of a retarded depression remaining. Recovery from the depression followed a period of several months' hospitalization under psychiatric régime. During the acute toxicity the superimposed psychosis sufficiently masked the depression that it was not detected. This unusual method of attempted suicide provided opportunity to study the physiologic effects of massive, prolonged thyroid overdosage—a case of experimental human hyperthyroidism.
Matrine induces caspase-independent program cell death in hepatocellular carcinoma through bid-mediated nuclear translocation of apoptosis inducing factor
Authors: Huan Zhou, Minying Xu, Ya Gao, Zhigang Deng, Hanwei Cao, Wenqing Zhang, Qiao Wang, Bing Zhang, Gang Song, Yanyan Zhan, Tianhui Hu
Journal: Molecular Cancer (2014)

Matrine, a clinical drug in China, has been used to treat viral hepatitis, cardiac arrhythmia and skin inflammations. Matrine also exhibits chemotherapeutic potential through its ability to trigger cancer cell death. However, the mechanisms involved are still largely unknown. The objective of this study was to investigate the major determinant for the cell death induced by matrine in human hepatocellular carcinoma. We use human hepatocellular carcinoma cell line HepG2 and human hepatocellular carcinoma xenograft in nude mice as models to study the action of matrine in hepatocellular cancers. We found that caspase-dependent and -independent Program Cell Death (PCD) occurred in matrine-treated HepG2 cells, accompanied by the decreasing of mitochondrial transmembrane potential and the increasing ROS production. Further studies showed that AIF released from the mitochondria to the nucleus, and silencing of AIF reduced the caspase-independent PCD induced by matrine. What's more, AIF nuclear translocation, and the subsequent cell death as well, was prevented by Bid inhibitor BI-6C9, Bid-targeted siRNA and ROS scavenger Tiron. In the in vivo study, matrine significantly attenuated tumor growth with AIF release from mitochondria into nucleus in nude mice. These data imply that matrine potently induce caspase-independent PCD in HepG2 cells through Bid-mediated AIF translocation.
Invasive group A streptococcal infection in pregnancy
Authors: Takahiro Yamada, Takashi Yamada, Mie K. Yamamura, Kenichi Katabami, Mineji Hayakawa, Utano Tomaru, Shigeki Shimada, Mamoru Morikawa, Toshio Seki, Satoshi Ariga, Kaoru Ishikawa, Tadayoshi Ikebe, Satoshi Gando, Hisanori Minakami
Journal: Journal of Infection (2010)
AZTREONAM IN CAPD PERITONITIS
Authors: M. Dratwa, Y. Glupczynski, N. Lameire, D. Matthys, G. Verschraegen, M. Van Eeckhoute, J. Boelaert, M. Schurgers, H. Van Landuyt, D. Verbeelen, S. Lauwers
Journal: The Lancet (1987)
Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment. Possible role of early coronary atherosclerosis.
Authors: H Yasue, K Matsuyama, K Matsuyama, K Okumura, Y Morikami, H Ogawa
Journal: Circulation (1990)

We examined the response of left coronary arteries to intracoronary injection of acetylcholine (ACh) 50 micrograms in 74 patients by measuring the diameter changes with a videodensitometric analysis system. Patients with angiographically normal coronary arteries were subdivided into a younger group of 26 patients (age, 9-29 years) and an older group of 23 patients (age, 31-68 years). In the younger group, the diameter at the distal segment of the left anterior descending artery (LAD) and at the proximal, middle, and distal segments of the left circumflex artery (LCx) increased significantly (16.7 +/- 19.3%, p less than 0.01, for LAD and 8.0 +/- 18.8%, p less than 0.05; 11.0 +/- 16.1%, p less than 0.01; and 19.8 +/- 17.5%, p less than 0.01, for LCx segments, respectively) in response to ACh. In the older group, on the other hand, the diameter at the proximal and middle segments of LAD and LCx decreased significantly (-20.8 +/- 16.9%, p less than 0.01; and -17.9 +/- 28.4%, p less than 0.01, for LAD segments and -14.6 +/- 17.4%, p less than 0.01; and -11.3 +/- 21.4%, p less than 0.05, for LCx segments, respectively). The dilator response to ACh in the younger group was significantly greater in the distal segment than in the proximal segment in both LAD and LCx (p less than 0.01 for LAD and p less than 0.05 for LCx). The constrictor response to ACh in the older group was significantly greater in the proximal than the distal segment in both LAD and LCx (p less than 0.05 for LAD and LCx, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Proapoptotic Bad and Bid Protein Expression Predict Survival in Stages II and III Colon Cancers
Authors: Frank A. Sinicrope, Rafaela L. Rego, Nathan R. Foster, Stephen N. Thibodeau, Steven R. Alberts, Harold E. Windschitl, Daniel J. Sargent
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Proapoptotic BH3-only proteins Bad and Bid initiate apoptosis by binding to regulatory sites on prosurvival Bcl-2 proteins to directly neutralize their function. We determined if expression of these proteins in colon cancers may account for differences in patient survival. Experimental Design: Tumor-node-metastasis stages II and III primary colon carcinomas from patients treated in 5-fluorouracil-based adjuvant therapy trials were studied. Immunohistochemical analysis of Bad and Bid proteins was done in tumors (n = 379) and adjacent normal mucosa. Expression was correlated with clinicopathologic variables, disease-free survival rates (DFS), and overall survival (OS) rates. Results: High expression of the Bad protein [hazard ratio (HR), 0.64; 95% confidence interval (95% CI), 0.43-0.96; P = 0.031] in the cytoplasm of tumor cells was significantly associated with more favorable OS in a univariate analysis. The combined Bad and Bid variable was prognostic for DFS (P = 0.027) and OS (P = 0.006). Stage and histologic grade, but not DNA mismatch repair status, were also prognostic for OS. Multivariate Cox analysis showed that high expression of Bad (HR, 0.64; 95% CI, 0.43-0.97; P = 0.027) and Bid (HR, 0.68; 95% CI, 0.49-0.97; P = 0.034) were independent predictors of OS after adjustment for stage, grade, age, treatment, and study. The combined variable of Bad + Bid was independently associated with DFS (P = 0.020) and OS (P = 0.004). Conclusion: Proapoptotic Bad and Bid proteins are independent prognostic variables in colon cancer patients receiving adjuvant treatment. If validated, Bad and Bid expression may assist in risk stratification and selection of patients to receive adjuvant chemotherapy.
Lip papillomatosis in immunodeficiency: therapy with imiquimod
Authors: D. Rinne, C. Linhart, H. Schöfer
Journal: British Journal of Dermatology (2000)

Sir, Human papillomaviruses (HPVs) can cause a wide variety of cutaneous and mucosal tumours. Current treatments are non‐specific and include tumour ablation by cryotherapy, electrocautery or laser, surgical excision, cytodestruction with podophyllin or podophyllotoxin, and immunotherapy with topical or injectable interferon (IFN).1 We report our experience with imiquimod (Aldara® 5% cream, Laboratoires 3M Santé, Cergy, France), a new immunomodulatory substance, in refractory papillomas of the lip in an immunodeficient patient. A 43‐year‐old woman presented with a 5‐year history of papillomas on the lower lip (Fig. 1a). Known underlying diseases were human immunodeficiency virus (HIV) infection (CDC stage B3), epilepsy, diabetes mellitus since 1992, and hepatitis B and C infection since 1997. Her HIV infection had been treated with a triple combination of zidovudine, lamivudine and nevirapine for 7 months, her epilepsy with carbamazepine, and her diabetes with insulin. Examination revealed extensive, fissured, hyperplastic, verrucous papillomas on the lower lip. No HPV‐induced papillomas were detected at other sites. Punch biopsies of the lower lip were performed. Histology showed typical features of virus‐induced papillomas, and immunohistochemical assay (polyclonal antibody to papillomavirus, BioGenex, Hamburg, Germany) was HPV‐positive.
Successes and Challenges in Translational Research: The Development of Targeted Therapy for Gastrointestinal Stromal Tumours
Authors: Daniel J. Renouf, Lora Wilson, Charles D. Blanke
Journal: Clinical Cancer Research (2009)

Abstract Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms that most commonly affect the stomach or small intestine, but that can occur anywhere within the gastrointestinal tract. The annual incidence of GISTs is estimated to be 10 to 20 cases per million. Traditionally, the only effective treatment was surgical resection, and recurrences were common even with complete removal of tumor. Systemic therapy with standard cytotoxic chemotherapeutic agents was completely ineffective. A series of exciting laboratory developments led to the discovery that the small molecule tyrosine kinase inhibitor STI571 (imatinib mesylate) has significant clinical activity in GISTs, representing one of the first therapeutic uses of a targeted agent directed against a solid tumor. In this article we will describe the key steps that led to the initial clinical trials of imatinib in GISTs, and we will also discuss the process of incorporating this novel therapy into mainstream oncologic practice.
Pretreatment macrophage infiltration of the synovium predicts the clinical effect of both radiation synovectomy and intra-articular glucocorticoids
Authors: Z N Jahangier
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To explore whether pretreatment features of synovial tissue in patients with gonarthritis could predict the clinical effect of radiation synovectomy with yttrium-90 (<sup>90</sup>Y) and glucocorticoids or with intra-articular glucocorticoids alone. <b>Methods:</b> A synovial biopsy was carried out blindly 2 weeks before treatment in 66 patients with persistent gonarthritis, who were randomised to treatment either with <sup>90</sup>Y and triamcinolone or with placebo and triamcinolone. Immunohistochemistry was used to detect T cells, macrophages, B cells, plasma cells, fibroblast-like synoviocytes, adhesion molecules and pro-inflammatory cytokines. Stained sections were evaluated by digital image analysis. Individual patient improvement was expressed using a composite change index (CCI; range 0–12). Successful treatment was defined as CCI ⩾6 after 6 months. <b>Results:</b> Patients with rheumatoid arthritis, psoriatic arthritis, undifferentiated arthritis and other causes of gonarthritis were included. The overall response rate was 47%. Clinical efficacy in both therapeutic groups was similar and not dependent on diagnosis. No significant differences were noted between baseline microscopic features of synovial tissue inflammation in patients with rheumatoid arthritis and in those with non-rheumatoid arthritis (ie, all diagnoses other than rheumatoid arthritis). The number of macrophages in the synovial sublining was significantly higher in responders than in non-responders (p = 0.002), independent of treatment group and diagnosis. The clinical effect was positively correlated with pretreatment total macrophage numbers (r = 0.28; p = 0.03), sublining macrophage numbers (r = 0.34; p = 0.005) and vascular cell adhesion molecule 1 expression (r = 0.25; p = 0.04). <b>Conclusion:</b> The observations support the view that intra-articular treatment either with <sup>90</sup>Y and glucocorticoids or with glucocorticoids alone is especially successful in patients with marked synovial inflammation.
Therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy
Authors: Nigel A. Calcutt, Karen L. Allendoerfer, Andrew P. Mizisin, Alicia Middlemas, Jason D. Freshwater, Monica Burgers, Rigel Ranciato, Jean-Dominique Delcroix, Frederick R. Taylor, Renee Shapiro, Kathy Strauch, Henryk Dudek, Thomas M. Engber, Alphonse Galdes, Lee L. Rubin, David R. Tomlinson
Journal: Journal of Clinical Investigation (2003)

Hedgehog proteins modulate development and patterning of the embryonic nervous system. As expression of desert hedgehog and the hedgehog receptor, patched-1, persist in the postnatal and adult peripheral nerves, the hedgehog pathway may have a role in maturation and maintenance of the peripheral nervous system in normal and disease states. We measured desert hedgehog expression in the peripheral nerve of maturing diabetic rats and found that diabetes caused a significant reduction in desert hedgehog mRNA. Treating diabetic rats with a sonic hedgehog–IgG fusion protein fully restored motor- and sensory-nerve conduction velocities and maintained the axonal caliber of large myelinated fibers. Diabetes-induced deficits in retrograde transport of nerve growth factor and sciatic-nerve levels of calcitonin gene–related product and neuropeptide Y were also ameliorated by treatment with the sonic hedgehog–IgG fusion protein, as was thermal hypoalgesia in the paw. These studies implicate disruption of normal hedgehog function in the etiology of diabetes-induced peripheral-nerve dysfunction and indicate that delivery of exogenous hedgehog proteins may have therapeutic potential for the treatment of diabetic neuropathy.
Précis of<i>Deduction</i>
Authors: Philip N. Johnson-Laird, Ruth M. J. Byrne
Journal: Behavioral and Brain Sciences (1993)

Abstract How do people make deductions? The orthodox view in psychology is that they use formal rules of inference like those of a “natural deduction” system. Deduction argues that their logical competence depends, not on formal rules, but on mental models. They construct models of the situation described by the premises, using their linguistic knowledge and their general knowledge. They try to formulate a conclusion based on these models that maintains semantic information, that expresses it parsimoniously, and that makes explicit something not directly stated by any premise. They then test the validity of the conclusion by searching for alternative models that might refute the conclusion. The theory also resolves long-standing puzzles about reasoning, including how nonmonotonic reasoning occurs in daily life. The book reports experiments on all the main domains of deduction, including inferences based on prepositional connectives such as “if” and “or,” inferences based on relations such as “in the same place as,” inferences based on quantifiers such as “none,” “any,” and “only,” and metalogical inferences based on assertions about the true and the false. Where the two theories make opposite predictions, the results confirm the model theory and run counter to the formal rule theories. Without exception, all of the experiments corroborate the two main predictions of the model theory: inferences requiring only one model are easier than those requiring multiple models, and erroneous conclusions are usually the result of constructing only one of the possible models of the premises.