tbuckley/cabot-search huggingface dataset:
An Address on Lanolin: A New Basis for Ointments
Authors: O. Liebreich
Journal: BMJ (1886)

GE;NTLEM1EN,-In presenting to you the stubstance lanolin as a new basis for oinitments, I am far fromi dleelaring that all questions touclh- ing its pharmacological usesare entirely solved.Lanolin is so peculiar a substance, that its varied employment will doubtless bring mla- new qualities to light-qualities which, as can already be foretold, belong: neither to glycerine-fats nor to mineral oils.However, the investigations I have made enable me to assert even now that lanolin is in cvery way a thoroughly efficient preparation for use in treatment by salves and ointments, and that it answers maniy requiroments whiclh the glycerinie-fats and mineral oils (such as vaseline) at present em- ployedlhave not been able to fulfil satisfactorily.The use of plasters and ointments, % hich at different times was con- sidered but a subordinate therapeutic method, has lately again been drawn into the domain of scientific research; treatment by local ap.plication being now esteenied of great value in various kinds of disease.If in what follows I speak of fats, tllese must be distinguished from the fatty substances so-called in a strictly chemnical sense.To quote Kekule's admirably precise definition: " The group of fatty substances embraces all bodies in which we can suppose the carbon atoms to be arranged in the simplest possible manner; " while, in a closer sense, those substances aro called fats which are separated into glycerine anid'
A systematic review and meta-analysis of efficacy and toxicity of disease modifying anti-rheumatic drugs and biological agents for psoriatic arthritis
Authors: V Ravindran, D L Scott, E H Choy
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> Treatments for psoriatic arthritis (PsA) range from high-cost agents such as tumour necrosis factor (TNF) inhibitors evaluated in large randomised control trials (RCTs) and low-cost disease-modifying anti-rheumatic drugs (DMARDs) studied in less detail. We compared their efficacy and toxicity in a systematic review. <h3>Methods:</h3> We searched Medline, PubMed and EmBase (1966–2006) for RCTs in PsA. We included RCTs that were randomised, placebo-controlled, in English, involved current treatments and only enrolled PsA patients. Efficacy was assessed by the numbers of patients withdrawn for lack of effect; toxicity by withdrawals for adverse events. RCTs were compared using risk ratios (RR) with 95% confidence intervals (CI). <h3>Results:</h3> We identified 32 potentially relevant RCTs; 14 were excluded because they involved unused agents, were unblinded, were not placebo-controlled and enrolled patients with other diseases. 18 studies were included in the meta-analysis assessing DMARD monotherapy (11), DMARD combinations (one), TNF inhibitors (five) and alefacept (one). Treatment was more effective than placebo (RR = 0.35; 95% CI 0.25, 0.49) but caused more toxicity (RR = 2.33; 95% CI 1.61, 3.37). There was evidence that gold, sulfasalazine, leflunomide and TNF inhibitors were effective; gold and TNF inhibitors showed the largest effect sizes; TNF inhibitors had the best efficacy/toxicity ratio (number needed to harm/number needed to treat = 0.25); tolerability was least with gold and leflunomide. <h3>Conclusions:</h3> Efficacy/toxicity ratios were highest with TNF inhibitors followed by leflunomide, gold and sulfasalazine. Gold, though effective, has excessive toxicity and sulfasalazine, though of low toxicity, was also relatively ineffective.
An ITAM-signaling pathway controls cross-presentation of particulate but not soluble antigens in dendritic cells
Authors: Daniel B. Graham, Linda M. Stephenson, Siu Kit Lam, Karry Brim, Hyang Mi Lee, Jhoanne Bautista, Susan Gilfillan, Shreeram Akilesh, Keiko Fujikawa, Wojciech Swat
Journal: The Journal of Experimental Medicine (2007)

Dendritic cells (DC) possess a unique capacity for presenting exogenous antigen on major histocompatibility class I, a process that is referred to as cross-presentation, which serves a critical role in microbial and tumor immunity. During cross-presentation, antigens derived from pathogen-infected or tumor cells are internalized and processed by DCs for presentation to cytotoxic T lymphocytes (CTLs). We demonstrate that a signaling pathway initiated by the immunoreceptor tyrosine–based activation motif (ITAM)–containing adaptors DAP12 and FcRγ utilizes the Vav family of Rho guanine nucleotide exchange factors (GEFs) for processing and cross-presentation of particulate, but not soluble, antigens by DCs. Notably, this novel pathway is crucial for processing and presentation of particulate antigens, such as those associated with Listeria monocytogenes bacteria, yet it is not required for antigen uptake. Mechanistically, we provide evidence that in DCs, Vav GEFs are essential to link ITAM-dependent receptors with the activation of the NOX2 complex and production of reactive oxygen species (ROS), which regulate phagosomal pH and processing of particulate antigens for cross-presentation. Importantly, we show that genetic disruption of the DAP12/FcRγ–Vav pathway leads to antigen presentation defects that are more profound than in DCs lacking NOX2, suggesting that ITAM signaling also controls cross-presentation in a ROS-independent manner.
Comprehensive Analysis of <i>CDKN2A</i> Status in Microdissected Urothelial Cell Carcinoma Reveals Potential Haploinsufficiency, a High Frequency of Homozygous Co-deletion and Associations with Clinical Phenotype
Authors: Emma J. Chapman, Patricia Harnden, Philip Chambers, Colin Johnston, Margaret A. Knowles
Journal: Clinical Cancer Research (2005)

Abstract Purpose: There are significant differences in reported frequencies, modes of inactivation, and clinical significance of CDKN2A in urothelial cell carcinoma (UCC). We aimed to address these issues by investigating all possible modes of inactivation and clinicopathologic variables in a single tumor panel. Experimental Design: Fifty microdissected UCCs were examined. CDKN2A gene dosage (quantitative real-time PCR), allelic status (microsatellite analysis), hypermethylation (methylation-specific PCR), mutation status (denaturing high-performance liquid chromatography and sequencing), protein expression (immunohistochemistry), and clinicopathologic variables (stage, grade, and disease recurrence during follow-up) were assessed. Results: Exon 2 was underrepresented in 20 of 46 (43%) and exon 1β in 21 of 46 (46%) of cases. Underrepresentation of exon 2 was accompanied by loss of heterozygosity (LOH) of 9p in 6 of 18 (30%) and of exon 1β in 11 of 19 assessable cases (58%). Overall, LOH of 9p was identified in 15/41 (37%). Homozygous deletion of exons 2 and 1β was detected in 16 of 46 (35%) and 10 of 46 tumors (22%), respectively. Co-deletion was most common, but exon 2–specific homozygous deletion was also detected. In tumors without homozygous deletion, p16 promoter hypermethylation was detected in 1 of 18 (6%). Hypermethylation of the p14ARF promoter or mutations in CDKN2A were not observed. Homozygous deletion of exon 2 or LOH on 9p were associated with invasion. Homozygous deletion of exon 2 or exon 1β was associated with recurrent disease. Conclusions: These results confirm CDKN2A as a clinically relevant target for inactivation in UCC and show that the true frequency of alteration is only revealed by comprehensive analysis. Our results suggest that CDKN2A may be haploinsufficient in human cancer.
Thalidomide!! A Musical
Authors: Aula Abbara, Huda Al-Hadithy
Journal: BMJ (2006)

T he thalidomide disaster of the 1960s and the subsequent cover ups of devastated lives is not the most obvious subject for a musical or even satire, yet this production works beautifully. Written by and starring Mat Fraser, who was a thalidomide baby, Thalidomide!! A Musical is a hilarious, poignant, and touching show that charts the life of Glyn (played by Fraser), and his quest for happiness with his childhood sweetheart, Katie (Anna Winslet), who is infatuated with him and his short arms. The two talented leads maintain the audience's interest throughout …
STUDIES ON THE BLOOD PROTEINS
Authors: S. H. Hurwitz, G. H. Whipple
Journal: The Journal of Experimental Medicine (1917)

The intoxication which develops as the result of a simple obstruction or a closed intestinal loop is accompanied by definite changes in the coagulable proteins of the blood serum. These changes consist essentially in an alteration in the normal albumin-globulin ratio; the globulin fraction is greatly increased and at times the normal relation of the two fractions may show a complete inversion. The increase in the globulin content of the blood serum is most marked in the animals which show some of the complications met with in loop animals,-rupture of the loop and peritonitis. In the latter conditions especially, the globulin increase is rapid and large. We believe this reaction to be of diagnostic value in acute infections attended by the sudden liberation and absorption of a toxic exudate. Infections and intoxications produced by inflammatory irritants are also accompanied by a rise in the blood globulins. This observation suggests that tissue disintegration with absorption of toxic products is responsible for the changes noted, and that bacterial invasion is important only in as far as it gives rise to toxic substances. Animals which have developed a tolerance to proteose intoxication following the periodic injection of small doses of proteose do not show a globulin increase. These experiments do not support the view that the rise in globulins observed in these experimental conditions is an expression of a resistance or tolerance developed by the animal. From the experimental evidence it seems more probable that the alteration in the partition of the blood protein fractions is one of the results of the metabolic disturbance which has been shown to occur in these conditions.
Expression of Surfactant Protein-C, S100A8, S100A9, and B Cell Markers in Renal Allografts
Authors: Michael Eikmans, Marian C. Roos-van Groningen, Yvo W.J. Sijpkens, Jan Ehrchen, Johannes Roth, Hans J. Baelde, Ingeborg M. Bajema, Johan W. de Fijter, Emile de Heer, Jan A. Bruijn
Journal: Journal of the American Society of Nephrology (2005)

The intent of this study was to identify genes of which expression during acute rejection is associated with progression to chronic allograft nephropathy using gene expression profiling. Ten patients who had graft loss through chronic allograft nephropathy (progression [PR] group) and 18 patients who had stable graft function over time (nonprogression [NP] group) were studied. Rejection severity and extent of infiltrating leukocytes in acute rejection biopsies were similar for both groups. Microarray analysis and real-time PCR validation showed that surfactant protein-C (SP-C), S100 calcium-binding protein A8 (S100A8), S100A9, and β-globin levels distinguished the two groups. Relationship between expression of B cell markers and prognosis was also examined. Location in the graft of the protein and mRNA expression of candidate genes was investigated. The prognostic value of mRNA transcripts was tested in an independent cohort of 43 rejection biopsies. mRNA and protein expression of S100A8 and S100A9 in infiltrating cells was significantly higher in the NP group compared with the PR group. Expression of SP-C was four-fold higher in the PR group and was detected in glomeruli. No association between B cell clusters and outcome was found. In the second group of acute rejection biopsies, SP-C mRNA levels predicted renal function course beyond 6 mo in multivariate analysis. Relatively high expression of S100A8 and S100A9 during acute rejection is associated with a favorable prognosis, and high SP-C expression is associated with an unfavorable prognosis. Messenger RNA transcripts complement the biopsy in the prediction of graft function deterioration.
Variations in glycosylation of von Willebrand factor with O-linked sialylated T antigen are associated with its plasma levels
Authors: Carina J. M. van Schooten, Cécile V. Denis, Ton Lisman, Jeroen C. J. Eikenboom, Frank W. Leebeek, Jenny Goudemand, Edith Fressinaud, H. Marijke van den Berg, Philip G. de Groot, Peter J. Lenting
Journal: Blood (2006)
Comparison of Cytogenetic and Molecular Genetic Detection of t(8;21) and inv(16) in a Prospective Series of Adults With De Novo Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
Authors: Krzysztof Mrózek, Thomas W. Prior, Colin Edwards, Guido Marcucci, Andrew J. Carroll, Pamela J. Snyder, Prasad R.K. Koduru, Karl S. Theil, Mark J. Pettenati, Kellie J. Archer, Michael A. Caligiuri, James W. Vardiman, Jonathan E. Kolitz, Richard A. Larson, Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To prospectively compare cytogenetics and reverse transcriptase–polymerase chain reaction (RT-PCR) for detection of t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22), aberrations characteristic of core-binding factor (CBF) acute myeloid leukemia (AML), in 284 adults newly diagnosed with primary AML. PATIENTS AND METHODS: Cytogenetic analyses were performed at local laboratories, with results reviewed centrally. RT-PCR for AML1/ETO and CBFβ/MYH11 was performed centrally. RESULTS: CBF AML was ultimately identified in 48 patients: 21 had t(8;21) or its variant and AML1/ETO, and 27 had inv(16)/t(16;16), CBFβ/MYH11, or both. Initial cytogenetic and RT-PCR analyses correctly classified 95.7% and 96.1% of patients, respectively (P = .83). Initial cytogenetic results were considered to be false-negative in three AML1/ETO-positive patients with unique variants of t(8;21), and in three CBFβ/MYH11-positive patients with, respectively, an isolated +22; del(16)(q22),+22; and a normal karyotype. The latter three patients were later confirmed to have inv(16)/t(16;16) cytogenetically. Only one of 124 patients reported initially as cytogenetically normal was ultimately RT-PCR–positive. There was no false-positive cytogenetic result. Initial RT-PCR was falsely negative in two patients with inv(16) and falsely positive for AML1/ETO in two and for CBFβ/MYH11 in another two patients. Two patients with del(16)(q22) were found to be CBFβ/MYH11-negative. M4Eo marrow morphology was a good predictor of the presence of inv(16)/t(16;16). CONCLUSION: Patients with t(8;21) or inv(16) can be successfully identified in prospective multi-institutional clinical trials. Both cytogenetics and RT-PCR detect most such patients, although each method has limitations. RT-PCR is required when the cytogenetic study fails; it is also required to determine whether patients with suspected variants of t(8;21), del(16)(q22), or +22 represent CBF AML. RT-PCR should not replace cytogenetics and should not be used as the only diagnostic test for detection of CBF AML because of the possibility of obtaining false-positive or false-negative results.
Imprint cytology improves accuracy of computed tomography-guided percutaneous transthoracic needle biopsy
Authors: Y-C. Chang, C-J. Yu, W-J. Lee, S-H. Kuo, C-H. Hsiao, I-S. Jan, F-C. Hu, H-M. Liu, W-K. Chan, P-C. Yang
Journal: European Respiratory Journal (2007)

The aim of the present study was to investigate whether imprint cytology can improve the diagnostic accuracy of computed tomography-guided transthoracic core biopsy. Between October 1997 and June 2004, thoracic lesions in 622 patients underwent biopsy using 19-gauge coaxial guiding needles and 20-gauge biopsy needles under computed tomography guidance. Touch imprint cytology and histopathology were performed for all biopsy specimens. Of these lesions, 431 (74.1%) were diagnosed as malignant, 151 (25.9%) as benign and 40 (6%) as nondiagnostic. Imprint cytology plus histology shows an improved diagnostic accuracy of 96.4% compared with that of imprint cytology alone (92.3%) or histopathology alone (93.0%). Procedure-related complications requiring further treatment occurred in eight (1.4%) patients. In conclusion, imprint cytology combined with histopathology can improve the diagnostic accuracy of computed tomography-guided transthoracic needle biopsy.
Acute Encephalopathy (Encephalitis) Complicating Rubella
Authors: Frank E. Sherman
Journal: JAMA (1965)

Rubella encephalopathy occurred in six children. This complication was estimated to have occurred in a ratio of 1:5,000 cases of rubella infection. Three children survived without sequelae; the other three died. Rubella virus was isolated from the throat of a survivor and from the lung of a child who subsequently died. Specimens had been collected on the sixth and seventh day after onset of rash, respectively. Other clinical and autopsy specimens, including brain, failed to yield virus. Antibodies against the rubella virus were demonstrated in the four cases from which serum was available. Cortisol-production rate was increased in the three patients, who subsequently died, who were treated with hypothermia, and was normal in a surviving patient with a milder case of rubella encephalopathy. Observations at autopsy revealed severe, nonspecific degeneration of the central nervous system but no changes specific for viral infection. The incidence and the clinical, virologic, and autopsy findings of this complication are contrasted with those of measles encephalitis.
Higher maintenance cyclosporine dose decreases the risk of graft failure in North American children
Authors: A Tejani, E K Sullivan
Journal: Journal of the American Society of Nephrology (1996)

Because of changing cyclosporine dosing patterns over the years, maintenance doses in 1469 living donor and 1486 cadaver donor index renal transplants in patients who were 0 to 20 yr of age of the time of transplantation were reviewed. All grafts had at least 30 days' function. Eighty-nine percent of living donor patients and 95% of cadaver donor patients were maintained on cyclosporine for 12 months after transplantation. Among patients receiving cyclosporine, the maintenance 12-month dose in living donor graft recipients increased from 6.4 mg/kg per day for patients who had transplants done in 1987 to 7.9 mg/kg per day for patients who had transplants done in 1992 (P = 0.02). Among cadaver donor graft recipients, the mean 12-month maintenance dose increased from 6.4 mg/kg per day in 1987 to 7.8 mg/kg per day in 1992 (P = 0.01). At 6 months after transplantation, the maintenance cyclosporine dose in 1103 living donor graft recipients who retained graft function during the subsequent 6-month period was 7.1 mg/kg per day, compared with a 6-month dose of 3.9 mg/kg per day in 28 patients who lost their graft in the subsequent 6-month period. For 1041 recipients of cadaver donor grafts who retained graft function through 12 months after transplantation, the 6-month maintenance cyclosporine dose was 7.4 mg/kg per day, compared with 5.4 mg/kg per day in 59 patients whose graft failed in the subsequent 6 months. In patients who did not have an acute rejection episode during the first 12 months after transplantation, the rate of subsequent "late" rejections was 22% for patients with a 12-month maintenance cyclosporine dose < or = 4.0 mg/kg per day, and 16% for patients whose 12-month maintenance cyclosporine dose exceeded 8.6 mg/kg per day. A proportional hazards regression analysis, using cyclosporine dose as a time-dependent covariate, showed that the hazard of graft failure was reduced 5 to 6% for each incremental increase of 1 mg/kg maintenance dose of cyclosporine (within the dose range studied) for both living and cadaver donor source transplants.
Improved Cardiovascular Risk Profile and Renal Function in Renal Transplant Patients after Randomized Conversion from Cyclosporine to Tacrolimus
Authors: Marika A. Artz, Johannes M.M. Boots, Gerry Ligtenberg, Joke I. Roodnat, Maarten H.L. Christiaans, Pieter F. Vos, Henk J. Blom, Fred C.G.J. Sweep, Pierre N.M. Demacker, Luuk B. Hilbrands
Journal: Journal of the American Society of Nephrology (2003)

Cyclosporine is considered to contribute to the high cardiovascular morbidity and mortality in patients after renal transplantation. Tacrolimus may be more favorable in this respect, but controlled data are scarce. In this prospective randomized study in 124 stable renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on cardiovascular risk factors and renal function were investigated. Follow-up was 6 mo. Statistical analysis was performed by ANOVA for repeated measurements. The serum creatinine level decreased from 137 +/- 30 micromol/L to 131 +/- 29 micromol/L (P < 0.01). Three months after conversion from cyclosporine to tacrolimus, mean BP significantly decreased from 104 +/- 13 to 99 +/- 12 mmHg (P < 0.001). Serum LDL cholesterol decreased from 3.48 +/- 0.80 to 3.11 +/- 0.74 mmol/L (P < 0.001,) and serum apolipoprotein B decreased from 1018 +/- 189 to 935 +/- 174 mg/L (P < 0.001). Serum triglycerides decreased from 2.11 +/- 1.12 to 1.72 +/- 0.94 mmol/L (P < 0.001). In addition, both rate and extent of LDL oxidation were reduced. The fibrinogen level decreased from 3638 +/- 857 to 3417 +/- 751 mg/L (P < 0.05). Plasma homocysteine concentration did not change. Three months after conversion, plasma fasting glucose level temporarily increased from 5.4 +/- 1.3 mmol/L to 5.8 +/- 1.9 mmol/L (P < 0.05). Conversion to tacrolimus resulted in a significant reduction of the Framingham risk score. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients has a beneficial effect on renal function, BP, serum concentration and atherogenic properties of serum lipids, and fibrinogen.
Contrasting Modes of Evolution of the Visual Pigments in Heliconius Butterflies
Authors: F. Yuan, G. D. Bernard, J. Le, A. D. Briscoe
Journal: Molecular Biology and Evolution (2010)

The adult compound eyes of passion-vine butterflies in the genus Heliconius contain one more UV opsin than other butterflies. Together with an 11-cis-3-hydroxyretinal chromophore, their four opsin genes UVRh1, UVRh2, BRh, and LWRh produce four rhodopsins that are UV-, blue-, or long wavelength absorbing. One of the Heliconius UV opsin genes, UVRh2, was found to have evolved under positive selection following recent gene duplication, using the branch-site test of selection. Using a more conservative test, the small-sample method, we confirm our prior finding of positive selection of UVRh2 and provide new statistical evidence of episodic evolution, that is, positive selection followed by purifying selection. We also newly note that one of the positively selected amino acid sites contains substitutions with known spectral tuning effects in avian ultraviolet- and violet-sensitive visual pigments. As this is one of a handful of described examples of positive selection of any specific gene in any butterfly where functional variation between copies has been characterized, we were interested in examining the molecular and physiological context of this adaptive event by examining the UV opsin genes in contrast to the other visual pigment genes. We cloned BRh and LWRh from 13 heliconiine species and UVRh1 and UVRh2 from Heliconius elevatus. In parallel, we performed in vivo epi-microspectrophotometric experiments to estimate the wavelength of peak absorbance, λmax, of several rhodopsins in seven heliconiine species. In contrast to UVRh2, we found both physiological and statistical evidence consistent with purifying selection on UVRh1, BRh, and LWRh along the branch leading to the common ancestor of Heliconius. These results underscore the utility of combining molecular and physiological experiments in a comparative context for strengthening evidence for adaptive evolution at the molecular level.
A phase II trial of weekly intravenous gemcitabine and cisplatin with continuous infusion fluorouracil in patients with metastatic renal cell carcinoma
Authors: C.M. George, N.J. Vogelzang, B.I. Rini, F.J. Geoffroy, P. Kollipara, W.M. Stadler
Journal: Annals of Oncology (2002)