tbuckley/cabot-search huggingface dataset:
Corneal Reconstruction with Tissue-Engineered Cell Sheets Composed of Autologous Oral Mucosal Epithelium
Authors: Kohji Nishida, Masayuki Yamato, Yasutaka Hayashida, Katsuhiko Watanabe, Kazuaki Yamamoto, Eijiro Adachi, Shigeru Nagai, Akihiko Kikuchi, Naoyuki Maeda, Hitoshi Watanabe, Teruo Okano, Yasuo Tano
Journal: New England Journal of Medicine (2004)

Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells. Transplantation of autologous corneal stem-cell sources is an alternative to allograft transplantation and does not require immunosuppression, but it is not possible in many cases in which bilateral disease produces total corneal stem-cell deficiency in both eyes. We studied the use of autologous oral mucosal epithelial cells as a source of cells for the reconstruction of the corneal surface.We harvested 3-by-3-mm specimens of oral mucosal tissue from four patients with bilateral total corneal stem-cell deficiencies. Tissue-engineered epithelial-cell sheets were fabricated ex vivo by culturing harvested cells for two weeks on temperature-responsive cell-culture surfaces with 3T3 feeder cells that had been treated with mitomycin C. After conjunctival fibrovascular tissue had been surgically removed from the ocular surface, sheets of cultured autologous cells that had been harvested with a simple reduced-temperature treatment were transplanted directly to the denuded corneal surfaces (one eye of each patient) without sutures.Complete reepithelialization of the corneal surfaces occurred within one week in all four treated eyes. Corneal transparency was restored and postoperative visual acuity improved remarkably in all four eyes. During a mean follow-up period of 14 months, all corneal surfaces remained transparent. There were no complications.Sutureless transplantation of carrier-free cell sheets composed of autologous oral mucosal epithelial cells may be used to reconstruct corneal surfaces and can restore vision in patients with bilateral severe disorders of the ocular surface.
RNA interference against influenza A (H1N1) virus
Authors: Yang Li, Cheng-Yuan Ma, Wei Liu, Ming-Yao Tian, Shucheng Hua, Ning-Yi Jin
Journal: European Respiratory Journal (2011)

Influenza virus is a RNA virus which causes human and animals to suffer influenza, leading to acute upper respiratory tract infection. The existing vaccines and drugs have limited role in the treatment of influenza virus subtype H1N1. We prepared the small interfering RNA targeting RNA polymerase (PA) gene of influenza A (H1N1) virus and studied its effect of inhibiting virus replication. We designed and synthesized three pairs of siRNA targeting PA gene of influenza A (H1N1) virus, as well as constructed expression plasmid pS-PA646, pS-PA841 and pS-PA1537, being transfected into MDCK cells and chicken embryos respectively and infected with influenza virus subtype H1N1, to detect effects of siRNA on inhibiting influenza virus replication. We conducted viral HA titer determination, real-time RT-PCR.  The results show that in the designed 3 pairs of siRNA, pS-PA1537 can inhibit the replication of influenza A (H1N1) virus in MDCK cells and chicken embryos, laying the foundation for the development of therapeutic agents resistant H1N1.
Lack of influence of fetal hemoglobin levels or erythrocyte indices on the severity of sickle cell anemia.
Authors: D R Powars, W A Schroeder, J N Weiss, L S Chan, S P Azen
Journal: Journal of Clinical Investigation (1980)

Persons with sickle cell anemia who have elevated fetal hemoglobin or lowered erythrocyte mean corpuscular volume are reputed to have less severe clinical manifestations and a greater probability of survival. This study examines the relationship between seven clinical indicators of morbidity in sickle cell anemia and seven hematological parameters that were collected from 214 patients. Risks of sickle cell crisis, acute chest syndrome, hospital admissions, cerebrovascular accident, aseptic necrosis, meningitis/septicemia, and death were used as indicators of morbidity. The hematological parameters included percent fetal hemoglobin, absolute fetal hemoglobin, percent hemoglobin A2, hemoglobin concentration, packed cell volume, mean corpuscular volume, and mean corpuscular hemoglobin concentration. Statistical analyses of the data showed no relationship between the hematological parameters and six of the seven clinical indicators of the severity of sickle cell anemia. The only significant finding was an increased risk of stroke in those patients with lower levels of fetal hemoglobin. Therefore, with this exception, there is no predictable relationship between morbidity and mortality in sickle cell anemia and levels of fetal hemoglobin or erythrocyte indices. Thus, the general belief that there is an association between severity of sickle cell anemia and the levels of fetal hemoglobin has not been established.
Hybridization Characteristics of Complementary RNAs Generated on Murine Myeloma DNA Templates&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A. Arthur Gottlieb, Doreen N. Tenney
Journal: JNCI Journal of the National Cancer Institute (1972)

Complementary RNAs (c-RNAs) were produced by Escherichia coli sigma-containing RNA polymerase acting on the DNA of murine myelomas MOPC-21 and Adj-PC-5. Annealing of these c-RNAs to each tumor DNA template, under conditions favoring formation of high guanine-cytosine-containing hybrids, revealed no difference in the amount of c-RNA-forming hybrids of this type with the DNA of either tumor. Normal mouse liver DNA could be readily distinguished by this technique.
Determinants of Mortality Among Postmenopausal Women in the Women's Health Initiative Who Report Rheumatoid Arthritis
Authors: Lewis H. Kuller, Rachel H. Mackey, Brian T. Walitt, Kevin D. Deane, V. Michael Holers, William H. Robinson, Jeremy Sokolove, Yuefang Chang, Simin Liu, Christine G. Parks, Nicole C. Wright, Larry W. Moreland
Journal: Arthritis & Rheumatology (2013)

Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD) and mortality. We measured anti-cyclic citrullinated peptide (anti-CCP) antibody levels and determined use of disease-modifying antirheumatic drugs (DMARDs) among women in the Women's Health Initiative (WHI). Using these data, we undertook this study to assess total mortality over 10 years of followup among white, black, or Hispanic women with self-reported RA in the WHI. Using stored baseline serum, we measured anti-CCP, rheumatoid factor (RF), and antinuclear antibodies (ANAs) in 9,988 women who reported having RA. Based on a previous chart review study, probable RA was defined as either self-reported RA and anti-CCP positivity, or anti-CCP negativity and DMARD use. Cox proportional hazards regression was used to model the relationship of self-reported RA, DMARD exposure, and anti-CCP positivity to total mortality, using followup data through April 2009. At baseline, the mean age was 62.8 years; 24.5% of subjects were black and 10% were Hispanic. Prevalence of anti-CCP positivity was 8.1% (n = 812), and 217 women were anti-CCP negative but had reported use of DMARDs; therefore, 1,029 women (of 9,988) were classified as having probable RA, and 8,958 were classified as unlikely to have RA (with data on DMARD use missing for 1 subject). Age-adjusted mortality rates were ∼2-fold higher for anti-CCP-positive women, with 20.2 deaths per 1,000 person-years, as compared to 11.4 deaths per 1,000 person-years among anti-CCP-negative women with self-reported RA who never used DMARDs. Among women who did not report any arthritis at baseline, we found 8.3 deaths per 1,000 person-years. The increased risk among anti-CCP-positive women with RA was not explained by age, RF positivity, ANA positivity, or DMARD use. Anti-CCP-positive RA was associated with substantial excess mortality among postmenopausal women in the WHI. This result was not explained by the risk factors we measured.
Plasminogen Activator Inhibitor-1 Regulates Myoendothelial Junction Formation
Authors: Katherine R. Heberlein, Adam C. Straub, Angela K. Best, Mark A. Greyson, Robin C. Looft-Wilson, Poonam R. Sharma, Akshaya Meher, Norbert Leitinger, Brant E. Isakson
Journal: Circulation Research (2010)

Plasminogen activator inhibitor-1 (PAI-1) is a biomarker for several vascular disease states; however, its target of action within the vessel wall is undefined.Determine the ability of PAI-1 to regulate myoendothelial junction (MEJ) formation.MEJs are found throughout the vasculature linking endothelial cells (ECs) and vascular smooth muscle cells. Using a vascular cell coculture we isolated MEJ fractions and performed two-dimensional differential gel electrophoresis. Mass spectrometry identified PAI-1 as being enriched within MEJ fractions, which we confirmed in vivo. In the vascular cell coculture, recombinant PAI-1 added to the EC monolayer significantly increased MEJs. Conversely, addition of a PAI-1 monoclonal antibody to the EC monolayer reduced the number of MEJs. This was also observed in vivo where mice fed a high fat diet had increased PAI-1 and MEJs and the number of MEJs in coronary arterioles of PAI-1(-/-) mice was significantly reduced when compared to C57Bl/6 mice. The presence of MEJs in PAI-1(-/-) coronary arterioles was restored when their hearts were transplanted into and exposed to the circulation of C57Bl/6 mice. Application of biotin-conjugated PAI-1 to the EC monolayer in vitro confirmed the ability of luminal PAI-1 to translocate to the MEJ. Functionally, phenylephrine-induced heterocellular calcium communication in the vascular cell coculture was temporally enhanced when recombinant PAI-1 was present, and prolonged when PAI-1 was absent.Our data implicate circulating PAI-1 as a key regulator of MEJ formation and a potential target for pharmacological intervention in diseases with vascular abnormalities (eg, diabetes mellitus).
B7H Costimulates Clonal Expansion of, and Cognate Destruction of Tumor Cells by, CD8+ T Lymphocytes In Vivo
Authors: Xingluo Liu, Xue-Feng Bai, Jing Wen, Jian-Xin Gao, Jinqing Liu, Ping Lu, Yin Wang, Pan Zheng, Yang Liu
Journal: The Journal of Experimental Medicine (2001)

B7H/B7RP (hereby called B7H) is a new member of the B7 family of costimulatory molecules and interacts with inducible costimulatory molecule (ICOS). Its function for CD8 T cells has not been reported. We report here that expression of B7H on the tumor cells reduced tumorigenicity and induced immunity to subsequent challenge with parental tumor cells. The immune protection correlates with an enhanced cytotoxic T lymphocyte (CTL) response against P1A, the major tumor antigen expressed in the J558 tumor. To understand the mechanism of immune protection, we adoptively transferred transgenic T cells specific for tumor antigen P1A into mice that bore P1A-expressing tumors. We found that while the transgenic T cells divided faster in mice bearing the B7H+ tumors, optimal B7H-induced clonal expansion of P1CTL required costimulation by B7–1 and B7–2 on the endogenous host antigen-presenting cells (APCs). Interestingly, when B7H+ and B7H− tumors were coinjected, P1CTL selectively eliminated the B7H+ tumor cells. Moreover, B7H expressed on the tumor cells made them highly susceptible to destruction by CTL in vivo, even if the CTL was administrated into mice with large tumor burdens. Tumors that recurred in the P1CTL-treated mice lost transfected B7H and/or H-2Ld, the class I molecule that presents the P1A peptide. Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8+ T lymphocytes in vivo.
The Effect of Pioglitazone on Peroxisome Proliferator-Activated Receptor-γ Target Genes Related to Lipid Storage In Vivo
Authors: Iwona Bogacka, Hui Xie, George A. Bray, Steven R. Smith
Journal: Diabetes Care (2004)

Pioglitazone is a member of the thiazolidinediones (TZDs), insulin-sensitizing agents used to treat type 2 diabetes. The aim of this study was to define the effect of pioglitazone on the expression of genes related to carbohydrate and lipid metabolism in subcutaneous fat obtained from type 2 diabetic patients.Forty-eight volunteers with type 2 diabetes were divided into two groups treated for 12 weeks with placebo or pioglitazone (30 mg/day). The expression of several genes was quantified by real-time RT-PCR.Pioglitazone treatment increased the expression of genes involved in glycerol-3-phosphate synthesis. The mRNA expression of PEPCK-C and glycerol-3-phosphate dehydrogenase (GPDH) increased (P < 0.01) in patients treated with pioglitazone. There was no difference in glycerol kinase (GyK) mRNA levels. The expression of genes that regulate fatty acid availability in adipocytes, including lipoprotein lipase (LPL) and acetyl-CoA synthetase (ACS), was higher (P < 0.01) in pioglitazone-treated patients. Pioglitazone stimulated (P < 0.0001) expression of c-Cbl-associated protein (CAP), whereas tumor necrosis factor-alpha, leptin, resistin, angiopoietin like-4, and 11-beta-hydroxysteroid dehydrogenase type 1 (11beta HSD 1) were not affected by pioglitazone. The baseline peroxisome proliferator-activated receptor (PPAR)-gamma1 mRNA was significantly correlated with mRNA for LPL, CAP, ACS, 11beta HSD 1, GyK, fatty acid synthase, leptin, and GPDH, whereas PPAR-gamma2 mRNA was correlated with CAP, PEPCK-C, leptin, and GPDH.Treatment with pioglitazone increased body weight, and this is associated with upregulation of some, but not all, genes previously demonstrated as "TZD responsive" in subcutaneous fat. The results suggest that TZDs might increase body weight through the upregulation of genes facilitating adipocyte lipid storage in vivo.
Etomoxir Improves Left Ventricular Performance of Pressure-Overloaded Rat Heart
Authors: Marian Turcani, Heinz Rupp
Journal: Circulation (1997)

Numerous studies have demonstrated diverse abnormalities in subcellular structures of pressure-overloaded hypertrophied and failing heart. Long-term administration of etomoxir, a carnitine palmitoyltransferase-1 inhibitor, partially normalized the proportion of myosin isozyme V1 and number of active Ca2+ pumps in hypertrophied rat myocardium.To test the hypothesis that long-term etomoxir treatment improves the performance of hypertrophied ventricle, sham-operated rats and rats with ascending aorta constriction were treated with racemic etomoxir (15 mg/kg per day) for 12 weeks. Left ventricular geometry, dynamics of isovolumic contractions, as well as myosin isozymes as marker of etomoxir-induced phenotype changes were assessed. Etomoxir stimulated (P<.05) slight hypertrophic growth in right and left ventricles of sham-operated rats as well as in right ventricles but not in overloaded left ventricles of rats with aortic constriction. In all treated rats, etomoxir increased (P<.05) maximal developed pressure, left ventricular pressure-volume area, and +/- dP/dt(max). Enhanced values (P<.05) of derived indexes of myocardial performance (normalized stress-length area, maximal rate of wall stress rise, and decline) indicated that myocardial changes were responsible for the improved performance. The etomoxir treatment increased selectively (P<.05) the proportion of myosin V1 in pressure-overloaded left ventricles.The long-term treatment with etomoxir improved functional capacity of pressure-overloaded left ventricle, which can be attributed to an enhanced myocardial performance. Chronic carnitine palmitoyltransferase-1 inhibition may thus represent a candidate approach for developing novel agents that are useful in the prevention of undesirable consequences of pressure overload-induced cardiac hypertrophy.
Omeprazole induction of cytochrome P-450IA2: The importance of selecting the appropriate human model
Authors: Paul B. Watkins
Journal: Hepatology (1993)

Omeprazole has been shown to induce cytochrome P450IA1 and P450IA2 activity in vitro. To reflect cytochrome P450IA2 (CYPIA2) activity in vivo, the 13 C-[ N -3-methyl]-caffeine breath test was conducted in 18 volunteers: 12 extensive metabolizers, one intermediate metabolizer, and five poor metabolizers of S -mephenytoin. Breath tests were performed before treatment with an oral dose of 40 mg omeprazole, on the seventh day of treatment, and after a 7-day washout period. The mean percentage exhalation of the 13 C test dose, as determined by 13 CO 2 in breath during 8 hours, was 23.0% ± 8.0% ( n = 18) before treatment. The largest increases in exhalation rate of 13 CO 2 were observed in the poor metabolizers and the intermediate metabolizers (range, 12.8% to 62.9%; median, 38.9%); median area under the plasma concentration-time curves (AUC) of omeprazole was four times higher than in the extensive metabolizers. The change after omeprazole treatment in extensive metabolizers ranged from −9.8% to + 47.7% (median, 12.3%; n = 12) of pretreatment values. In both groups, exhalation rates of 13 CO 2 returned to near pretreatment values within the 7-day washout period (24.2% ± 7.8%; n = 17). Changes in the 13 C-caffeine breath test correlated well with both the pretreatment value R = −0.67, p = 0.003; n = 18 and the plasma AUC of omeprazole ( R = 0.61, p = 0.007; n = 18). Therapeutic doses of omeprazole seem to induce CYP1A2 activity in poor metabolizers, whereas they exert minor inducing effects in extensive metabolizers of S-mephenytoin. CLIN Pharmacol Ther 1992;52:170-180.
Losartan Restores Skeletal Muscle Remodeling and Protects Against Disuse Atrophy in Sarcopenia
Authors: Tyesha N. Burks, Eva Andres-Mateos, Ruth Marx, Rebeca Mejias, Christel Van Erp, Jessica L. Simmers, Jeremy D. Walston, Christopher W. Ward, Ronald D. Cohn
Journal: Science Translational Medicine (2011)

Losartan improves muscle remodeling and protects against immobilization atrophy by mediating pathways critical for muscle homeostasis.
Epidemiology of and Risk Factors for Psychosis of Alzheimer’s Disease: A Review of 55 Studies Published From 1990 to 2003
Authors: Susan A. Ropacki, Dilip V. Jeste
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors reviewed studies published between 1990 and 2003 that reported the prevalence, incidence, and persistence of, as well as the risk factors associated with, psychosis of Alzheimer’s disease. METHOD: PubMed and PsycINFO databases were searched by using the terms “psychosis and Alzheimer disease” and “psychosis and dementia.” Empirical investigations presenting quantitative data on the epidemiology of and/or risk factors for psychotic symptoms in Alzheimer’s disease were included in the review. A total of 55 studies, including a total of 9,749 subjects, met the inclusion criteria. RESULTS: Psychosis was reported in 41% of patients with Alzheimer’s disease, including delusions in 36% and hallucinations in 18%. The incidence of psychosis increased progressively over the first 3 years of observation, after which the incidence seemed to plateau. Psychotic symptoms tended to last for several months but became less prominent after 1 year. African American or black ethnicity and more severe cognitive impairment were associated with a higher rate of psychosis. Psychosis was also associated with more rapid cognitive decline. Some studies found a significant association between psychosis and age, age at onset of Alzheimer’s disease, and illness duration. Gender, education, and family history of dementia or psychiatric illness showed weak or inconsistent relationships with psychosis. CONCLUSIONS: Psychotic symptoms are common and persistent in patients with Alzheimer’s disease. Improved methods have advanced the understanding of psychosis in Alzheimer’s disease, although continued research, particularly longitudinal studies, may unveil biological and clinical associations that will inform treatments for these problematic psychological disturbances.
Copper and Manganese Concentrations in Biliary Cirrhosis of Liver
Authors: M. Worwood, D. M. Taylor, A. H. Hunt
Journal: BMJ (1968)

The presence of large amounts of copper in the liver in primary biliary cirrhosis has been confirmed; a similar increase is not found in cases of long-standing extrahepatic biliary obstruction. The serum caeruloplasmin levels are raised in primary and secondary biliary cirrhosis, but this increase does not appear to be related to the degree of increase of hepatic copper. The manganese content of the liver is slightly raised in both these conditions.The reason for the increased metal content in these circumstances cannot yet be determined, and the effects are not yet understood.
Safety and Efficacy of INCB018424, a JAK1 and JAK2 Inhibitor, in Myelofibrosis
Authors: Srdan Verstovsek, Hagop Kantarjian, Ruben A. Mesa, Animesh D. Pardanani, Jorge Cortes-Franco, Deborah A. Thomas, Zeev Estrov, Jordan S. Fridman, Edward C. Bradley, Susan Erickson-Viitanen, Kris Vaddi, Richard Levy, Ayalew Tefferi
Journal: New England Journal of Medicine (2010)

Myelofibrosis is a Philadelphia chromosome–negative myeloproliferative neoplasm associated with cytopenias, splenomegaly, poor quality of life, and shortened survival. About half of patients with myelofibrosis carry a gain-of-function mutation in the Janus kinase 2 gene (JAK2 V617F) that contributes to the pathophysiology of the disease. INCB018424 is a potent and selective Janus kinase 1 (JAK1) and JAK2 inhibitor.We conducted a phase 1−2 trial of INCB018424 in patients with JAK2 V617F−positive or JAK2 V617F−negative primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis.A total of 153 patients received INCB018424 for a median duration of more than 14.7 months. The initial dose-escalation phase established 25 mg twice daily or 100 mg once daily as maximum tolerated doses, on the basis of reversible thrombocytopenia. A dose-dependent suppression of phosphorylated signal transducer and activator of transcription 3 (STAT3), a marker of JAK signaling, was demonstrated in patients with wild-type JAK2 and in patients with the JAK2 V617F mutation. We studied additional doses and established that a 15-mg twice-daily starting dose, followed by individualized dose titration, was the most effective and safest dosing regimen. At this dose, 17 of 33 patients (52%) had a rapid objective response (≥50% reduction of splenomegaly) lasting for 12 months or more, and this therapy was associated with grade 3 or grade 4 adverse events (mainly myelosuppression) in less than 10% of patients. Patients with debilitating symptoms, including weight loss, fatigue, night sweats, and pruritus, had rapid improvement. Clinical benefits were associated with a marked diminution of levels of circulating inflammatory cytokines that are commonly elevated in myelofibrosis.INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed. (Funded by Incyte; ClinicalTrials.gov number, NCT00509899.)