tbuckley/cabot-search huggingface dataset:
Raised serum prolactin levels associated with hirsutism and amenorrhoea.
Authors: M Seppala, E Hirvonen
Journal: BMJ (1975)

Praecordial leads of 19 year old girl (case 1).Upper: during episode of ventricular tachycardia.Lower.reversion to sinus rhythm during induction with 400 mg propanidid.to intravenous practolol, but this failed during an admission in November 1974.She reverted to sinus rhythm soon after receiving 400 mg propanidid.In March 1975 she was readmitted with a similar tachycardia.Five minutes after receiving 500 mg propanidid she again reverted to sinus rhythm.Case 3.-A 22-year-old woman with Fallot's tetralogy, reconstructed seven years earlier, developed a ventricular tachycardia.She failed to revert-with propanidid though her ventricular rate fell from 190 to 170 beats/min.Case 4.-A 64-year-old man with ischaemic heart disease developed ventric- ular tachycardia.He did not revert after 400 mg propanidid and D.C. shock was applied one minute later.Cases 5 and 6.-These two patients with atrial fibrillation also failed to revert after propanidid.Case 7.-This patient went into atrial fibrillation after a gastrectomy.The fibrillation spontaneously reverted to a supraventricular tachycardia.After 250 mg propanidid the patients went into atrial flutter.Thus propanidid failed to control the rhythm disturbance in cases 3 to 7. In case 7 it converted supraventricular tachycardia to atrial flutter. 3
Prevalence of chronic kidney disease and anemia among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort Study: Baseline results
Authors: David G. Warnock, William Mcclellan, Leslie A. Mcclure, Britt Newsome, Ruth C. Campbell, Paul Audhya, Mary Cushman, Virginia J. Howard, George Howard
Journal: Kidney International (2005)
A Prospective Randomized Trial of Outpatient versus Inpatient Cardiac Catheterization
Authors: Peter C. Block, Ira Ockene, Robert J. Goldberg, John Butterly, Elizabeth H. Block, Charlene Degon, Alexa Beiser, Theodore Colton
Journal: New England Journal of Medicine (1988)

To evaluate the safety and cost of outpatient cardiac catheterization, we conducted a randomized trial at three hospitals of outpatient (n = 192) as compared with inpatient (n = 189) cardiac catheterization in low-risk patients. Outpatients had the following complication rates as compared with inpatients: hematoma, 12 versus 8.5 percent; numbness or weakness of extremity, 0.5 versus 1.6 percent; cold or blue extremity, 1.6 versus 1.1 percent; and acute myocardial infarction, 1.6 versus 0.5 percent. None of these differences were statistically significant. No deaths or strokes occurred in either group. Twenty-three patients (12 percent) assigned to the outpatient group required hospitalization because of complications of catheterization. In the outpatient group, the relative risk for hematoma was 1.42 (95 percent confidence interval, 0.77 to 2.29), and the relative risk for myocardial infarction within one week was 2.95 (95 percent confidence interval, 0.3 to 28.1). There were no significant differences between the two groups in whether they resumed normal activities or in the rates of rehospitalization within one week of the procedure. Total catheterization-related charges per patient were $679 lower for outpatients, with a savings in total hospital charges (including charges for subsequent therapeutic procedures) of $885 per patient. We conclude that elective cardiac catheterization as an outpatient procedure for selected patients is feasible and safe. Given the small size of our sample, however, we urge caution in interpreting these findings, since they do not exclude a small increase in complication rates with outpatient cardiac catheterization. (N Engl J Med 1988; 319:1251–5.)
The antimalarial ferroquine is an inhibitor of hepatitis C virus
Authors: Thibaut Vausselin, Noémie Calland, Sandrine Belouzard, Véronique Descamps, Florian Douam, François Helle, Catherine François, Dimitri Lavillette, Gilles Duverlie, Ahmed Wahid, Lucie Fénéant, Laurence Cocquerel, Yann Guérardel, Czeslaw Wychowski, Christophe Biot, Jean Dubuisson
Journal: Hepatology (2013)

Hepatitis C virus (HCV) is a major cause of chronic liver disease. Despite recent success in improving anti-HCV therapy, additional progress is still needed to develop cheaper and interferon (IFN)-free treatments. Here, we report that ferroquine (FQ), an antimalarial ferrocenic analog of chloroquine, is a novel inhibitor of HCV. FQ potently inhibited HCV infection of hepatoma cell lines by affecting an early step of the viral life cycle. The antiviral activity of FQ on HCV entry was confirmed with pseudoparticles expressing HCV envelope glycoproteins E1 and E2 from six different genotypes. In addition to its effect on HCV entry, FQ also inhibited HCV RNA replication, albeit at a higher concentration. We also showed that FQ has no effect on viral assembly and virion secretion. Using a binding assay at 4°C, we showed that FQ does not prevent attachment of the virus to the cell surface. Furthermore, virus internalization was not affected by FQ, whereas the fusion process was impaired in the presence of FQ as shown in a cell-cell fusion assay. Finally, virus with resistance to FQ was selected by sequential passage in the presence of the drug, and resistance was shown to be conferred by a single mutation in E1 glycoprotein (S327A). By inhibiting cell-free virus transmission using a neutralizing antibody, we also showed that FQ inhibits HCV cell-to-cell spread between neighboring cells. Combinations of FQ with IFN, or an inhibitor of HCV NS3/4A protease, also resulted in additive to synergistic activity.FQ is a novel, interesting anti-HCV molecule that could be used in combination with other direct-acting antivirals.
Amegakaryocytic thrombocytopenia of 4 years duration: Successful treatment with antithymocyte globulin
Authors: Malcolm S. Trimble, Michael C. Brain, Michael F. X. Glynn
Journal: American Journal of Hematology (1991)

Abstract Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare cause of thrombocytopenia. Since it is a syndrome of diverse etiologies, the optimal treatment is often uncertain. In a patient with longstanding AATP, a complete remission was obtained with antithymocyte globulin.
Preexisting Conditions 'Hold Americans Hostage' to Employers and Insurance
Authors: Paul Cotton
Journal: JAMA (1991)

"MILLIONS OF hardworking, honest Americans are being held hostage by insurance companies. I am one of them." So begins a letter to President George Bush from Mary Evans, a Columbus, Ohio, woman with an increasingly common tale to tell: Savings wiped out after payment denials for treatment of preexisting conditions (in Evans' case, surgery to remove breast cancer that her insurer says she "should have" found before she had to switch policies because of her husband's job change); Fear that recurrence would require a bone marrow transplant she could not afford if her insurance would not pay; Disgust with what Evans calls the "mountain of paperwork" and "snippy, haughty, surly" treatment from insurance companies; No apparent way out. If she dared to change insurers, a new policy would almost surely exclude cancer coverage. "If you have the misfortune of getting a catastrophic illness, you are literally held hostage by the
Possible Role of Semaphorin 3F, a Candidate Tumor Suppressor Gene at 3p21.3, in p53-Regulated Tumor Angiogenesis Suppression
Authors: Manabu Futamura, Hiroki Kamino, Yuji Miyamoto, Noriaki Kitamura, Yasuyuki Nakamura, Shiho Ohnishi, Yoshiko Masuda, Hirofumi Arakawa
Journal: Cancer Research (2007)

Abstract Although the regulation of tumor angiogenesis is believed to be one of the core functions of p53, the mechanism still remains to be elucidated. Here, we report that semaphorin 3F (SEMA3F), an axon guidance molecule, is involved in p53-regulated antiangiogenesis. The expression level of SEMA3F mRNA was increased by both exogenous and endogenous p53. Chromatin immunoprecipitation assay indicated that a potent p53-binding sequence in intron 1 of SEMA3F interacts with p53 and that it has a p53-responsive transcriptional activity. Overexpression of SEMA3F inhibited in vitro cell growth of the lung cancer cell line H1299. In nude mice assay, the size of the H1299 tumors expressing SEMA3F was much smaller, and they showed lesser number of blood vessels as compared with the control tumors. Moreover, tumors derived from the p53-knockdown colorectal cancer cell line LS174T displayed a remarkable enhancement of tumor vessel formation as compared with control tumors containing normal levels of p53. The expression levels of SEMA3F and neuropilin-2 (NRP2), the functional receptor for SEMA3F, in p53-knockdown LS174T tumors were lower than those in the control tumors. Adenovirus-mediated SEMA3F gene transfer induced the remarkable in vitro growth suppression of the stable transformant of H1299 cells, which express high levels of NRP2. These results suggest that p53 negatively regulates tumor vessel formation and cell growth via the SEMA3F-NRP2 pathway. [Cancer Res 2007;67(4):1451–9]
Voluntary Sterilization in the Male
Authors: C. P. Blacker
Journal: BMJ (1968)

Formidable and remarkable is  assortment of disorders which your correspondent Dr. H.J. Roberts of Palm Beach Florida attributes (17 August p.434) to  voluntary sterilization of young men.  The assortment includes graves diseases such as severe narcolepsy and multiple sclerosis; it includes common conditions such as prolonged fever and recurrent infection; and it includes such imprecisely defined disturbances as various  skin eruptions and  biological false-positive serologic reaction.  Apart from hypoglycaemia the only common  was vasectomy.  By questioning every individual with such  features declares your correspondent a history of vasectomy prior to their onset has been uncovered.  How many men I wonder suffering from unexplained thrombophlebitis and increased circulatory gammaglobulin to quote two more of  13 conditions attributed by Dr. Roberts to  past vasectomy did he see who who had not been  vasectomized?  Do we not want to know how many before we incriminate  surgery?  Dr. Roberts argument recalls those of many sincere opponents of new practices such as vaccination and birth control.  You believe them to be harmful.  You may also believe them to be evil - it being easy to hold that if  practice is evil it must also be harmful.  Your patients come to yor with miscellaneous ailments.  You question them about  suspected evil practice and when acknowledgement is forthcoming you are easily convinced that  practice is  cause of  ailment.  You then conclude perhaps with more fervour than logic that the only common denominator was...the evil practice (vasectomy for example).  If after vasectomy seminal products are absorbed into  system and if (as suggested by your correspondent) they cause adverse reactions could not these reactions be identified with minimum risk of misinterpretation by carefully  following up  sample of vasectomized men?  Could not Dr. Roberts persuade  (American) Association for Voluntary Sterilization In. to undertake  follow-up?  This they may have already done.  The association had mediated  vasectomy of may men and had kept good records.(Full text)
Vertebral artery occlusion and oral contraceptives.
Authors: E Ask-Upmark, E R Bickerstaff
Journal: BMJ (1976)

If vertebral artery occlusion occurs in degenerative arterial disease it is almost invariably left-sided, but in vertebral artery deficiency syndromes associated with oral contraceptives a striking preponderance of right-sided involvement has been shown. This observation adds support to the view that causes other than changes in the wall of the vessel at the site of occlusion must be sought as an explanation of the occlusion.
Diffuse Soft Tissue Uptake of I-131 After Post-Thyroidectomy Ablation Therapy for Thyroid Cancer
Authors: HO-CHEON SONG, YOUNG-JUN HEO, SEONG-MIN KIM, HEE-SEUNG BOM
Journal: Clinical Nuclear Medicine (2002)

SONG, HO-CHEON M.D., Ph.D.; HEO, YOUNG-JUN M.D.; KIM, SEONG-MIN M.D.; BOM, HEE-SEUNG M.D., Ph.D. Author Information
BH3 Inhibitor Sensitivity and Bcl-2 Dependence in Primary Acute Lymphoblastic Leukemia Cells
Authors: Sarah E. Alford, Anisha Kothari, Floris C. Loeff, Joshua M. Eichhorn, Nandini Sakurikar, Henriette M. Goselink, Robert L. Saylors, Inge Jedema, J.H. Frederik Falkenburg, Timothy C. Chambers
Journal: Cancer Research (2015)

BH3 mimetic drugs may be useful to treat acute lymphoblastic leukemia (ALL) but the sensitivity of primary tumor cells has not been fully evaluated. Here, B-lineage ALL cell cultures derived from a set of primary tumors were studied with respect to sensitivity to the BH3 mimetics ABT-263 and ABT-199 and to Bcl-2 dependence and function. These ALL cells each expressed high levels of Bcl-2 and exhibited great sensitivity to ABT-263 and ABT-199, which induced rapid apoptotic cell death. BH3 profiling indicated that the ALL cultures were Bcl-2 dependent. Coimmunoprecipitation studies revealed a multifaceted role for Bcl-2 in binding proapoptotic partners including Bax, Bak, Bik, and Bim. ABT-263 disrupted Bcl-2:Bim interaction in cells. Mcl-1 overexpression rendered ALL cells resistant to ABT-263 and ABT-199, with Mcl-1 assuming the role of Bcl-2 in binding Bim. Freshly isolated pediatric ALL blasts also expressed high levels of Bcl-2 and exhibited high sensitivity to Bcl-2 inhibition by the BH3 mimetic compounds. Overall, our results showed that primary ALL cultures were both more sensitive to BH3 mimetics and more uniform in their response than established ALL cell lines that have been evaluated previously. Furthermore, the primary cell model characterized here offers a powerful system for preclinical testing of novel drugs and drug combinations to treat ALL.
A9.15 Remission as the Main Therapeutic Target: Comparative Efficacy of Four Treatment Regimens in Early Rheumatoid Arthritis (RA) Patients (Pts)
Authors: E Fedorenko, G Lukina, Y Sigidin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Early RA contains the "the window of opportunities" for achieving the best results of therapy including remissions. It is very important to determine the influence of different treatment regimens on the remission rate in patients (pts) with early RA. <h3>Objectives</h3> To compare development of remissions in pts with early (&lt;2 years duration) RA who were randomly assigned to receive four different strategies of DMARDs treatment. <h3>Methods</h3> One hundred forty-one pts with RA of less than 2 years duration (122 women, mean age 51 years, mean disease duration 24 weeks, mean DAS28 5.9; 64% RF-positive, 59% ACCP-positive) were randomised to receive one of the following treatment regimens: methotrexate (MTX, up to 20 mg/week, 35 pts); MTX plus prednisolone (P) 10 mg daily (MTX-P, 34 pts); MTX-P plus methylprednisolone (MP) 1000 mg intravenously on the first day of treatment (MTX-P-MP, 35 pts); leflunomide 20 mg daily (LEF, 37 pts). Duration of treatment was one year. Efficacy of therapy was assessed by EULAR criteria. Control points were 3, 6 and 12 months from the beginning of therapy. The primary endpoint was the development of remission. <h3>Results</h3> At baseline all groups were comparable in their demographic, clinical and radiographic characteristics. One hundred twenty-seven pts completed the study. By the 3d month in the MTX group only 3.1% of the patients reached clinical remission, while in the combination groups of MTX with GC (including MP intravenously) 21.3% and 28.6%, respectively. By the 6th month the same tendency continued: combination of MTX with GC showed the greatest frequency of remissions – 33.3% and 23.5%, respectively. In the MTX and LEF monotherapy groups the corresponding figures were 15.2% and 20.6%, respectively. By the 12th month the frequency of remissions was significantly higher in pts treated with the combination of MTX and GC, including high doses of MP (37.5% and 29.4%, respectively) than in the MTX and LEF monotherapy groups (11.4% and 16.2%, respectively). <h3>Conclusions</h3> In pts with early RA combined treatment with MTX and GC led to the significantly higher remission rate as compared with MTX and LEF monotherapy.
Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells through Modulation of the Phosphatidylinositol 3-Kinase Pathway
Authors: Lynn S. Adams, Sheryl Phung, Natalie Yee, Navindra P. Seeram, Liya Li, Shiuan Chen
Journal: Cancer Research (2010)

Dietary phytochemicals are known to exhibit a variety of anticarcinogenic properties. This study investigated the chemopreventive activity of blueberry extract in triple-negative breast cancer cell lines in vitro and in vivo. Blueberry decreased cell proliferation in HCC38, HCC1937, and MDA-MB-231 cells with no effect on the nontumorigenic MCF-10A cell line. Decreased metastatic potential of MDA-MB-231 cells by blueberry was shown through inhibition of cell motility using wound-healing assays and migration through a polyethylene terephthalate membrane. Blueberry treatment decreased the activity of matrix metalloproteinase-9 and the secretion of urokinase-type plasminogen activator while increasing tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 secretion in MDA-MB-231 conditioned medium as shown by Western blotting. Cell signaling pathways that control the expression/activation of these processes were investigated via Western blotting and reporter gene assay. Treatment with blueberry decreased phosphatidylinositol 3-kinase (PI3K)/AKT and NFkappaB activation in MDA-MB-231 cells, where protein kinase C and extracellular signal-regulated kinase (ERK) were not affected. In vivo, the efficacy of blueberry to inhibit triple-negative breast tumor growth was evaluated using the MDA-MB-231 xenograft model. Tumor weight and proliferation (Ki-67 expression) were decreased in blueberry-treated mice, where apoptosis (caspase-3 expression) was increased compared with controls. Immunohistochemical analysis of tumors from blueberry-fed mice showed decreased activation of AKT and p65 NFkappaB signaling proteins with no effect on the phosphorylation of ERK. These data illustrate the inhibitory effect of blueberry phytochemicals on the growth and metastatic potential of MDA-MB-231 cells through modulation of the PI3K/AKT/NFkappaB pathway.
Molecular Evidence for Independent Origin of Multifocal Neuroendocrine Tumors of the Enteropancreatic Axis
Authors: Terrence M. Katona, Timothy D. Jones, Mingsheng Wang, Fadi W. Abdul-Karim, Oscar W. Cummings, Liang Cheng
Journal: Cancer Research (2006)

Abstract Neuroendocrine tumors of the enteropancreatic axis are often multifocal. We have investigated whether multifocal intestinal carcinoid tumors and multifocal pancreatic endocrine tumors arise independently or whether they originate from a single clone with subsequent intramural or intrapancreatic spread. Twenty-four cases, including 16 multifocal intestinal carcinoid tumors and eight multifocal pancreatic endocrine tumors, were studied. Genomic DNA samples were prepared from 72 distinct tumor nodules using laser capture microdissection. Loss of heterozygosity (LOH) assays were done using markers for putative tumor suppressor genes located on chromosomes 9p21 (p16), 11q13 (MEN1), 11q23 (SDHD), 16q21, 18q21, and 18q22-23. In addition, X chromosome inactivation analysis was done on the tumors from eight female patients. Twenty-two of 24 (92%) cases showed allelic loss in at least one tumor focus, including 15 of 16 (94%) cases of multifocal carcinoid tumors and 7 of 8 (88%) cases of multifocal pancreatic endocrine tumors. Eleven of 24 (46%) cases exhibited a different LOH pattern for each tumor. Additionally, 9 of 24 (38%) cases showed different LOH patterns among some of the coexisting tumors, whereas other coexisting tumors displayed the same allelic loss pattern. Two of 24 (8%) cases showed the same LOH pattern in every individual tumor. X chromosome inactivation analysis showed a discordant pattern of nonrandom X chromosome inactivation in two of six informative cases and concordant pattern of nonrandom X chromosome inactivation in the four remaining informative cases. Our data suggest that some multifocal neuroendocrine tumors of the enteropancreatic axis arise independently, whereas others originate as a single clone with subsequent local and discontinuous metastasis. (Cancer Res 2006; 66(9): 4936-42)
Oncogene activation in experimental carcinogenesis: the role of carcinogen and tissue specificity.
Authors: S J Garte, A E Hochwalt
Journal: Environmental Health Perspectives (1989)

Techniques of molecular biology have been used to determine the relationship of cellular oncogenes to mechanisms of experimental carcinogenesis. Model systems involving three direct-acting alkylating carcinogens, two organ sites, and two species have been employed to elucidate the relationships between carcinogenic etiology, tissue specificity, and activation of known and novel oncogenes. Dimethylcarbamyl chloride, a reactive acylating agent, induces tumors of both the rat nasal mucosa and mouse skin whose DNA is devoid of NIH 3T3 transforming activity. Beta-propiolactone-induced rat nasal carcinomas contain a novel oncogene, 6 to 9 kb in size, whereas a mouse skin carcinoma induced by this agent possesses an H-ras oncogene activated by a 61st codon A to T transversion mutation. The novel oncogene activated in rat nasal tumors induced by beta-propiolactone is distinct from one found in methylmethane sulfonate-induced tumors. The implications of these findings for understanding how oncogenes fit into general mechanism of carcinogenesis are discussed.
Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis.
Authors: Y Fujikawa, A Sabokbar, S Neale, N A Athanasou
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To determine whether synovial macrophages and monocytes isolated from patients with rheumatoid arthritis patients are capable of differentiating into osteoclastic bone resorbing cells; and the cellular and humoral conditions required for this to occur. METHODS: Macrophages isolated from the synovium and monocytes from the peripheral blood of rheumatoid arthritis patients were cultured on bone slices and coverslips, in the presence and absence of UMR 106 rat osteoblast-like cells, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and macrophage colony stimulating factor (M-CSF), and assessed for cytochemical and functional evidence of osteoclast differentiation. RESULTS: Isolated calcitonin receptor (CTR), tartrate resistant acid phosphatase (TRAP), and vitronectin receptor (VNR) negative, CD11b and CD14 positive monocytes and macrophages differentiated into CTR, TRAP, and VNR positive multinucleated cells capable of extensive lacunar bone resorption when co-cultured for 14 d with UMR 106 cells in the presence 1,25(OH)2D3 and M-CSF. CONCLUSIONS: Mononuclear phagocytes (monocytes and macrophages) from rheumatoid arthritis patients are capable of differentiating into multinucleated cells showing all the cytochemical and functional criteria of mature osteoclasts. Synovial macrophage-osteoclast differentiation may represent an important cellular mechanism in the bone destruction associated with rheumatoid arthritis.