tbuckley/cabot-search huggingface dataset:
Immediate and late phase allergic cutaneous reactions are not inducers of unspecific or specific local hyperreactivity
Authors: M. Andersson, U. Pipkorn
Journal: Allergy (1988)

The present study evaluates the possibility of allergen‐induced unspecific and specific dermal hyperreactivity with special reference to the presence of late cutaneous reactions and allergen‐induced nasal hyperreactivity. Twenty‐six patients with strictly seasonal allergic rhinitis participated. All had a positive skin prick test for birch ( Betula verrucosa ) and/or timothy ( Phleum pretense ). Ten patients had previously displayed an allergen‐induced nasal hyperreactivity and six patients a late cutaneous reaction. An initial skin prick test with a relevant pollen allergen was done in triplicate. The immediate skin reactions were recorded after 15 min and any late‐phase reaction after 6 h. Twenty‐four hours later the patients were retested. The same pollen allergen was sited in the first flare reaction from the previous day. A histamine prick test was sited in the weal as well as in the third reaction from day 1. A histamine control was also performed in a previously unaffected area. The allergen‐induced weal reactions decreased significantly at re‐challenge compared with the results from the previous day ( P &lt; 0.05). The histamine tests resulted in similar skin reactions regardless of whether or not they were done on a previous allergen test site. This was true for both specific and unspecific reactions when the subgroups of patients with previously demonstrated allergen‐induced nasal hyperreactivity or late‐phase skin reactions were evaluated separately. These results indicate that allergen‐induced hyperreactivity is not a general feature of allergic inflammation but is a phenomenon restricted to specific sites, such as the airway mucosa.
Cardiac Geometry and Function in Diabetic or Prediabetic Adolescents and Young Adults
Authors: Marina De Marco, Giovanni de Simone, Mary J. Roman, Marcello Chinali, Elisa T. Lee, Darren Calhoun, Barbara V. Howard, Richard B. Devereux
Journal: Diabetes Care (2011)

The aim of this study was to evaluate whether diabetes (DM) and impaired fasting glucose (IFG) were associated with early alterations in left ventricular geometry and function in a large population of adolescents and young adults independently of major confounders.We analyzed echocardiographic data of 1,624 14- to 39-year-old participants (mean age 26.6 ± 7.7 years; 57% female) without prevalent cardiovascular disease from the fourth Strong Heart Study examination; 179 (11%) participants had DM and 299 (18%) had IFG.Participants with DM and IFG were older and more often obese and hypertensive than participants with normal fasting glucose (NFG) (all P < 0.05). After adjustment for age, sex, systolic blood pressure, and body fat, diabetic and IFG participants had higher left ventricular mass index than those with NFG (41.5 ± 8.7 and 39.6 ± 9.2 vs. 35.6 ± 7.8 g/m(2.7)) and reduced stress-corrected midwall shortening (98 ± 8.6 and 99 ± 7.5 vs. 101 ± 8.5%; all P < 0.05). The prevalence of left ventricular hypertrophy was higher in DM (20%) and IFG (17%) than in NFG participants (12%; P < 0.05). Compared with the other groups, DM was also associated with higher prevalence of inappropriate left ventricular mass, concentric geometry, and more diastolic abnormalities independently of covariates (all P < 0.05).In a population of adolescents and young adults, DM is independently associated with early unfavorable cardiovascular phenotype characterized by increased left ventricular mass, concentric geometry, and early preclinical systolic and diastolic dysfunction; early cardiovascular alterations are also present in participants with prediabetes.
Somatic Mutations in <i>BRCA1</i> and <i>BRCA2</i> Could Expand the Number of Patients That Benefit From Poly (ADP Ribose) Polymerase Inhibitors in Ovarian Cancer
Authors: Bryan T.J. Hennessy, Kirsten M. Timms, Mark S. Carey, Alexander Gutin, Larissa A. Meyer, Darl D. Flake, Victor Abkevich, Jennifer Potter, Dmitry Pruss, Pat Glenn, Yang Li, Jie Li, Ana Maria Gonzalez-Angulo, Karen Smith McCune, Maurie Markman, Russell R. Broaddus, Jerry S. Lanchbury, Karen H. Lu, Gordon B. Mills
Journal: Journal of Clinical Oncology (2010)

The prevalence of BRCA(1/2) mutations in germline DNA from unselected ovarian cancer patients is 11% to 15.3%. It is important to determine the frequency of somatic BRCA(1/2) changes, given the sensitivity of BRCA-mutated cancers to poly (ADP ribose) polymerase-1 (PARP1) inhibitors and platinum analogs.In 235 unselected ovarian cancers, BRCA(1/2) was sequenced in 235, assessed by copy number analysis in 95, and tiling arrays in 65. 113 tumors were sequenced for TP53. BRCA(1/2) transcript levels were assessed by quantitative polymerase chain reaction in 220. When available for tumors with BRCA(1/2) mutations, germline DNA was sequenced.Forty-four mutations (19%) in BRCA1 (n = 31)/BRCA2 (n = 13) were detected, including one homozygous BRCA1 intragenic deletion. BRCA(1/2) mutations were particularly common (23%) in high-grade serous cancers. In 28 patients with available germline DNA, nine (42.9%) of 21 and two (28.6%) of seven BRCA1 and BRCA2 mutations were demonstrated to be somatic, respectively. Five mutations not previously identified in germline DNA were more commonly somatic than germline (four of 11 v one of 17; P = .062). There was a positive association between BRCA1 and TP53 mutations (P = .012). BRCA(1/2) mutations were associated with improved progression-free survival (PFS) after platinum-based chemotherapy in univariate (P = .032; hazard ratio [HR] = 0.65; 95% CI, 0.43 to 0.98) and multivariate (P = .019) analyses. BRCA(1/2) deficiency, defined as BRCA(1/2) mutations or expression loss (in 24 [13.3%] BRCA(1/2)-wild-type cancers), was present in 67 ovarian cancers (30%) and was also significantly associated with PFS in univariate (P = .026; HR = 0.67; 95% CI, 0.47 to 0.96) and multivariate (P = .008) analyses.BRCA(1/2) somatic and germline mutations and expression loss are sufficiently common in ovarian cancer to warrant assessment for prediction of benefit in clinical trials of PARP1 inhibitors.
Identification and measurement of molecular variants of cholecystokinin in duodenal mucosa and plasma. Diminished concentrations in patients with celiac disease.
Authors: J Calam, A Ellis, G J Dockray
Journal: Journal of Clinical Investigation (1982)

The amount and type of cholecystokinin (CCK) in duodenal extracts and plasma of celiac patients and normal subjects was studied by radioimmunoassay and gel filtration. In both groups there were similar patterns of molecular forms in extracts of duodenal biopsies, but concentrations in celiac disease were significantly depressed. In boiling water extracts of duodenal mucosa from both groups a factor with the properties of the COOH-terminal octapeptide of cholecystokinin predominated, but there were also significant amounts of a larger molecular weight form. In acid extracts of mucosa a factor with the properties of the 33 or 39 residue form was identified in amounts that were approximately 25% those of CCK8; there were also similar amounts of an acid-soluble form that had an apparent molecular weight higher than CCK39. Plasma immunoreactive cholecystokinin was studied after concentration by immunoaffinity adsorption and fractionation by gel filtration. In normal subjects fasting CCK-like immunoreactivity was less than 0.8 pmol/liter, and after a light breakfast increased to 2.0 +/- 0.7 (range 1.0 to 4.8) pmol/liter; CCK8-like activity accounted for all the increased immunoreactivity. In five of six celiac patients the concentrations of both fasting and postprandial CCK-like immunoreactivity in plasma were undetectable (less than 0.8 pmol/liter). We conclude that diminished production and release of CCK could account for the impaired pancreatic and gall bladder responses to intraluminal stimuli in celiac disease.
Lithium in the Prevention of Suicidal Behavior and All-Cause Mortality in Patients With Mood Disorders: A Systematic Review of Randomized Trials
Authors: Andrea Cipriani, Heather Pretty, Keith Hawton, John R. Geddes
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Observational studies suggest that long-term lithium treatment has a strong antisuicidal effect in mood disorders, but it is uncertain whether this association is a genuine therapeutic effect or is due to confounding factors in nonrandomized studies. The authors conducted a systematic review and meta-analysis of randomized trials to investigate the effect of lithium, compared to placebo and other active treatments, on the risk of suicide, deliberate self-harm, and all-cause mortality in patients with mood disorder. METHOD: The data source was the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE (1966–June 2002), EMBASE (1980–June 2002), CINAHL (1982–March 2001), PsycLIT (1974–June 2002), PSYNDEX (1977–October 1999), and LILACS (1982–March 2001). The Cochrane Central Register of Controlled Trials (CENTRAL) was searched with the term “lithium” for new records entered into the database from 1999 to 2003. Studies selected included randomized, controlled trials comparing lithium with placebo or all other compounds used in long-term treatment for mood disorders (unipolar depression, bipolar disorder, schizoaffective disorder, dysthymia, and rapid cycling, diagnosed according to DSM or ICD criteria). Of 727 references identified in the search, 52 articles were marked as possibly relevant on the basis of the abstract, and 32 randomized, controlled trials were eligible for inclusion in the review. Two independent reviewers extracted the data, and disagreements were resolved by consensus with a third reviewer. Methodological quality was assessed according to the criteria of the Cochrane Collaboration. When the outcomes of interest were not reported, an attempt was made to obtain the required data from the original authors. RESULTS: In 32 trials, 1,389 patients were randomly assigned to receive lithium and 2,069 to receive other compounds. Patients who received lithium were less likely to die by suicide (data from seven trials; two versus 11 suicides; odds ratio=0.26; 95% confidence interval [CI]=0.09–0.77). The composite measure of suicide plus deliberate self-harm was also lower in patients who received lithium (odds ratio=0.21; 95% CI=0.08–0.50). There were fewer deaths overall in patients who received lithium (data from 11 trials; nine versus 22 deaths; odds ratio=0.42, 95% CI=0.21–0.87). CONCLUSIONS: Lithium is effective in the prevention of suicide, deliberate self-harm, and death from all causes in patients with mood disorders.
Determination of <i>TP53</i> Mutation Is More Relevant Than Microsatellite Instability Status for the Prediction of Disease-Free Survival in Adjuvant-Treated Stage III Colon Cancer Patients
Authors: Jantine L. Westra, Michael Schaapveld, Harry Hollema, Jelle P. de Boer, Marian M.J. Kraak, Debora de Jong, Arja ter Elst, Nanno H. Mulder, Charles H.C.M. Buys, Robert M.W. Hofstra, John T.M. Plukker
Journal: Journal of Clinical Oncology (2005)

Purpose Microsatellite instability (MSI), TP53 mutation, and KRAS mutation status have been reported as prognostic factors in colon cancer. Most studies, however, have included heterogeneous groups of patients with respect to cancer stage. We determined the prognostic relevance of high-frequency MSI (MSI-H), TP53 mutations, and KRAS mutations in a well-defined group of patients with stage III colon cancer (N = 391), randomly assigned for adjuvant treatment with fluorouracil-based chemotherapy. Methods Three hundred ninety-one tumor specimens were available. MSI was determined in 273 specimens, and mutation analyses of TP53 and KRAS were performed in 220 and 205 specimens, respectively. Results In a univariate analysis, MSI-H (44 of 273; 16%) was associated with a longer disease-free survival (DFS; P = .038), but in a multivariate model adjusting for nodal involvement, histology, invasion, and grade of tumor, the association of MSI status with DFS did no longer reach statistical significance, though the risk estimate for microsatellite stability versus MSI-H tumors did not change much. Mutant TP53, found in 116 (53%) of 220 tumors, was associated with a shorter DFS, both in univariate (P = .009) and multivariate analyses (P = .018), whereas KRAS mutations (58 of 205; 28%) did not show any prognostic significance. Conclusion Both mutant TP53 and MSI-H seem to be prognostic indicators for disease-free survival, but only TP53 retains statistical significance after adjusting for clinical heterogeneity. Thus, in adjuvantly treated patients with stage III colon cancer, presence or absence of a TP53 mutation should be considered as a better predictor for DFS than MSI status.
Effects of Tetrahydrobiopterin on Endothelial Dysfunction in Rats with Ischemic Acute Renal Failure
Authors: MASAO KAKOKI, YASUNOBU HIRATA, HIROSHI HAYAKAWA, ETSU SUZUKI, DAISUKE NAGATA, AKIHIRO TOJO, HIROAKI NISHIMATSU, NOBUO NAKANISHI, YOSHIYUKI HATTORI, KAZUYA KIKUCHI, TETSUO NAGANO, MASAO OMATA
Journal: Journal of the American Society of Nephrology (2000)

The role of nitric oxide (NO) in ischemic renal injury is still controversial. NO release was measured in rat kidneys subjected to ischemia and reperfusion to determine whether (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4), a cofactor of NO synthase (NOS), reduces ischemic injury. Twenty-four hours after bilateral renal arterial clamp for 45 min, acetylcholine-induced vasorelaxation and NO release were reduced and renal excretory function was impaired in Wistar rats. Administration of BH4 (20 mg/kg, by mouth) before clamping resulted in a marked improvement of those parameters (10-8 M acetylcholine, Δrenal perfusion pressure: sham-operated control -45 ± 5, ischemia -30 ± 2, ischemia + BH4 -43 ± 4%; ΔNO: control +30 ± 6, ischemia +10 ± 2, ischemia + BH4 +23 ± 4 fmol/min per g kidney; serum creatinine: control 23 ± 2, ischemia 150 ± 27, ischemia + BH4 48 ± 6 μM; mean ± SEM). Most of renal NOS activity was calcium-dependent, and its activity decreased in the ischemic kidney. However, it was restored by BH4 (control 5.0 ± 0.9, ischemia 2.2 ± 0.4, ischemia + BH4 4.3 ± 1.2 pmol/min per mg protein). Immunoblot after low-temperature sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the dimeric form of endothelial NOS decreased in the ischemic kidney and that it was restored by BH4. These results suggest that the decreased activity of endothelium-derived NO may worsen the ischemic tissue injury, in which depletion of BH4 may be involved.
Nicotinic Acid as Therapy for Dyslipidemia in Non—Insulin-Dependent Diabetes Mellitus
Authors: Abhimanyu Garg, Scott M. Grundy
Journal: JAMA (1990)

Recently, nicotinic acid has been recommended as a first-line hypolipidemic drug. To determine the effectiveness of nicotinic acid in dyslipidemic patients with non—insulin-dependent diabetes mellitus, 13 patients were treated in a randomized crossover trial. Patients received either nicotinic acid (1.5 g three times daily) or no therapy (control period) for 8 weeks each. Compared with the control period, nicotinic acid therapy reduced the plasma total cholesterol level by 24%, plasma triglyceride level by 45%, very-low-density lipoprotein cholesterol level by 58%, and low-density lipoprotein cholesterol level by 15% and it increased the high-density lipoprotein cholesterol level by 34%. However, nicotinic acid therapy resulted in the deterioration of glycemic control, as evidenced by a 16% increase in mean plasma glucose concentrations, a 21% increase in glycosylated hemoglobin levels, and the induction of marked glycosuria in some patients. Furthermore, a consistent increase in plasma uric acid levels was observed. Therefore, despite improvement in lipid and lipoprotein concentrations, because of worsening hyperglycemia and the development of hyperuricemia, nicotinic acid must be used with caution in patients with non—insulin-dependent diabetes mellitus with dyslipidemia. We suggest that the drug not be used as a first-line hypolipidemic drug in patients with non—insulin-dependent diabetes mellitus. (<i>JAMA</i>. 1990;264:723-726)
Primary chemotherapy in operable breast cancer with favorable prognostic factors: A pilot study evaluating the efficacy of a regimen with a low subjective toxic burden containing vinorelbine, 5-fluorouracil and folinic acid (FLN)
Authors: F. Nolè, I. Minchella, M. Colleoni, E. Orvieto, E. Munzone, F. de Braud, G. Peruzzotti, G. Martinelli, M.G. Zampino, C. Catania, M. Pizzamiglio, P. Veronesi, S. Zurrida, V. Galimberti, A. Goldhirsch, U. Veronesi
Journal: Annals of Oncology (1999)
Automatic annotation of eukaryotic genes, pseudogenes and promoters.
Authors: Victor Solovyev, Peter Kosarev, Igor Seledsov, Denis Vorobyev
Journal: Genome biology (2006)

Abstract Background The ENCODE gene prediction workshop (EGASP) has been organized to evaluate how well state-of-the-art automatic gene finding methods are able to reproduce the manual and experimental gene annotation of the human genome. We have used Softberry gene finding software to predict genes, pseudogenes and promoters in 44 selected ENCODE sequences representing approximately 1% (30 Mb) of the human genome. Predictions of gene finding programs were evaluated in terms of their ability to reproduce the ENCODE-HAVANA annotation. Results The Fgenesh++ gene prediction pipeline can identify 91% of coding nucleotides with a specificity of 90%. Our automatic pseudogene finder (PSF program) found 90% of the manually annotated pseudogenes and some new ones. The Fprom promoter prediction program identifies 80% of TATA promoters sequences with one false positive prediction per 2,000 base-pairs (bp) and 50% of TATA-less promoters with one false positive prediction per 650 bp. It can be used to identify transcription start sites upstream of annotated coding parts of genes found by gene prediction software. Conclusion We review our software and underlying methods for identifying these three important structural and functional genome components and discuss the accuracy of predictions, recent advances and open problems in annotating genomic sequences. We have demonstrated that our methods can be effectively used for initial automatic annotation of the eukaryotic genome.
ETIOLOGY OF OROYA FEVER
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1928)

Bartonella muris appeared in the blood of all white rats, wild rats, Chinese hamster, and mice, from which the spleen was removed, but did not appear in that of splenectomized monkeys, rabbits, or guinea pigs. It has not been possible to transmit B. muris to normal rats, monkeys, rabbits, or guinea pigs, by intraperitoneal, intradermal, or intravenous injection of blood containing B. muris from splenectomized rats. In two instances an acute orchitis was induced in normal rats by injection directly into the testicle of blood or saline suspensions of the liver of splenectomized rats. The intracorpuscular elements occasionally identified as B. muris or as having appeared as a result of the inoculation. The acute orchitis of rats was transferable to normal rats in series. From the testicular tissue, as well as directly from the blood of a splenectomized rat, there was isolated in pure culture a microorganism which induced in the testicles of normal rats an acute orchitis such as resulted from inoculation of the blood or liver suspensions of splenectomized rats. While a few inclusions were found in the erythrocytes of some of the animals, their number was so small and their occurence so infrequent that they could not be definitely identified as B. muris. In morphological features the cultural forms of the microorganism isolated resemble B. muris. The organism found in the testicular tissues, however, is considerably coarser than B. muris and takes a deeper stain. Immunological study failed to settle the question of the relation between B. muris and the cultivated organism, which is provisionally called Bacterium murium. Bartonella muris, Bartonella bacilliformis, and Grahamella talpae have characteristic individual morphological features.
Oropharyngeal flora and chest infection after upper abdominal surgery.
Authors: J P Dilworth, R J White, E M Brown
Journal: Thorax (1991)

The oropharyngeal flora was determined before and after operation in 127 patients undergoing upper abdominal surgery. Swabs of the oropharynx were obtained on the day before operation and on the first, third, and fifth postoperative days. Isolation of Haemophilus influenzae, Streptococcus pneumoniae, and coliforms was noted. In the 108 patients with the full series of throat swabs the incidence of oropharyngeal colonisation by H influenzae was 16% and was unchanged after operation. S pneumoniae was present in only 5.6 (six patients) before operation and the incidence fell to 1.9% (two patients). There was a transient rise in coliform colonisation postoperatively. Twenty four patients developed a chest infection. In eight a bacterial cause was established, in six H influenzae and in two S pneumoniae. There was a significant relation between the carriage of H influenzae before operation and development of a chest infection. H influenzae was also found more often in cigarette smokers. The presence of S pneumoniae or coliform organisms before surgery was not related to the development of infection. The high incidence of postoperative chest infection in cigarette smokers appears to be due in part to preoperative colonisation of the oropharynx by H influenzae.
Patient-Specific Modeling of Cardiovascular Mechanics
Authors: C.A. Taylor, C.A. Figueroa
Journal: Annual Review of Biomedical Engineering (2009)

Advances in numerical methods and three-dimensional imaging techniques have enabled the quantification of cardiovascular mechanics in subject-specific anatomic and physiologic models. Patient-specific models are being used to guide cell culture and animal experiments and test hypotheses related to the role of biomechanical factors in vascular diseases. Furthermore, biomechanical models based on noninvasive medical imaging could provide invaluable data on the in vivo service environment where cardiovascular devices are employed and on the effect of the devices on physiologic function. Finally, patient-specific modeling has enabled an entirely new application of cardiovascular mechanics, namely predicting outcomes of alternate therapeutic interventions for individual patients. We review methods to create anatomic and physiologic models, obtain properties, assign boundary conditions, and solve the equations governing blood flow and vessel wall dynamics. Applications of patient-specific models of cardiovascular mechanics are presented, followed by a discussion of the challenges and opportunities that lie ahead.