tbuckley/cabot-search huggingface dataset:
Myelodysplastic Syndrome and Benzene Exposure Among Petroleum Workers: An International Pooled Analysis
Authors: A. R. Schnatter, D. C. Glass, G. Tang, R. D. Irons, L. Rushton
Journal: JNCI Journal of the National Cancer Institute (2012)

Benzene at high concentrations is known to cause acute myeloid leukemia (AML), but its relationship with other lymphohematopoietic (LH) cancers remains uncertain, particularly at low concentrations. In this pooled analysis, we examined the risk of five LH cancers relative to lower levels of benzene exposure in petroleum workers.
The role of antigen mobility in anti-Rh0(D)-induced agglutination.
Authors: E J Victoria, E A Muchmore, E J Sudora, S P Masouredis
Journal: Journal of Clinical Investigation (1975)

Intact human erythrocytes were cross-linked with glutaraldehyde (GA) or dimethyladipimidate (DMA) and tested for their ability to bind [125I]-IgG anti-Rh0(D) and to undergo antibody-mediated hemagglutination. There was no decrease in antibody binding after treatment with GA concentrations up to 1.25% and DMA concentrations up to 1%. Red cells treated with these concentrations of GA and DMA did not agglutinate. The techniques employed to induce agglutination of the cross-linked red cells involved "incomplete" IgG anti-Rho (D) in albumin, "complete" IgM anti-D Rho (D) in saline, and the antiglobulin (Coombs) reaction. The agglutinability of the chemically modified red cells was inversely correlated with the extent of fixation. The dissociation of antibody binding from agglutinability in cross-linked erythrocytes suggests that Rho (D) antigen mobility is required for red cell agglutination. Antigen mobility was manifested by the transition from a relatively monodisperse distribution pattern of Rho (D) antigen sites to one of large aggregates or clusters when agglutination was induced by IgM anti-Rho (D), IgG anti-Rho (D) agglutination of protease modified red cells, and by anti-IgG agglutination of IgG anti-Rho (D)-coated red cells. Antigen clustering was not as prominent in red cells agglutinated by IgG anti-Rho (D) in the presence of albumin. Even though antigen mobility is a prerequisite for antibody-mediated hemagglutination, clustering does not appear to be an absolute requirement. The degree of antigen clustering differs with varying types of agglutination.
Regulation of interferon receptor expression in human blood lymphocytes in vitro and during interferon therapy.
Authors: A S Lau, G E Hannigan, M H Freedman, B R Williams
Journal: Journal of Clinical Investigation (1986)

Interferons (IFN) elicit antiviral and antineoplastic activities by binding to specific receptors on the cell surface. The binding characteristics of IFN to human lymphocytes were studied using IFN alpha 2 labeled with 125I to high specific activity. The specific binding curves generated were analyzed by the LIGAND program of Munson and Rodbard to determine receptor numbers. The number of receptors in peripheral blood lymphocytes (PBL) and tonsillar B-lymphocytes (TBL) from normal individuals were 505 +/- 293 (n = 10) and 393 +/- 147 (n = 3) respectively. When these cells were preincubated in vitro with unlabeled IFN alpha 2, the receptor number decreased to 82 +/- 45 and 61 +/- 16 respectively. Receptor binding activities recovered gradually over a period of 72 h when the cells were incubated in IFN-free medium. This recovery of receptors could be blocked by the addition of actinomycin D to the incubation medium. A similar decrease in receptor expression was observed in vivo in PBL from patients being treated daily with 5 X 10(6) units/m2 per d of IFN alpha 2 by subcutaneous injection, for acute lymphoblastic leukemia or papilloma virus infections. Receptor numbers in PBL in vivo were further reduced concurrent with the progression of IFN therapy. Thus the reduction in IFN receptor expression observed in vitro can be demonstrated in vivo. These studies indicate that monitoring IFN receptor expression in vivo can provide information regarding the availability of IFN receptors at the cell surface for the mediation of IFN actions during the course of IFN therapy.
Risperidone Maintenance Treatment in Schizophrenia: A Randomized, Controlled Trial
Authors: Chuan-Yue Wang, Yu-Tao Xiang, Zhuo-Ji Cai, Yong-Zhen Weng, Qi-Jing Bo, Jing-Ping Zhao, Tie-Qiao Liu, Gao-Hua Wang, Shi-Min Weng, Hong-Yan Zhang, Da-Fang Chen, Wai-Kwong Tang, Gabor S. Ungvari
Journal: American Journal of Psychiatry (2010)

Prevention of relapse is the crucial task in the maintenance treatment of schizophrenia. The investigators in this study sought to determine the duration of maintenance treatment needed with the initial therapeutic dose, in contrast to a reduced dose.In a multicenter open-label, randomized, controlled study, patients with schizophrenia who were clinically stabilized following an acute episode were randomly assigned to a no-dose-reduction group (initial optimal therapeutic dose continued throughout the study), a 4-week group (initial optimal therapeutic dose continued for 4 weeks, followed by a 50% dose reduction that was maintained until the end of the study), or a 26-week group (initial optimal therapeutic dose continued for 26 weeks, followed by a 50% dose reduction until the end of the study). All patients continued until the last recruited patient completed the 1-year follow-up.Of the 404 patients who met the entry criteria and were randomly assigned, 374 completed the study. The estimated mean time from entry to relapse was 571 days in the 4-week group, 615 days in the 26-week group, and 683 days in the no-dose-reduction group, with estimated relapse rates of 30.5%, 19.5%, and 9.4%, respectively. Patients in the no-dose-reduction group experienced greater reduction in the severity of psychotic symptoms.Patients who continued to receive the full risperidone dose used for their acute episode had fewer relapses than those who had dose reductions after 4 weeks or 26 weeks during the maintenance period. There was negligible difference in side effects among the three groups.
The Dynamic Ups and Downs of Genome Size Evolution in Brassicaceae
Authors: M. A. Lysak, M. A. Koch, J. M. Beaulieu, A. Meister, I. J. Leitch
Journal: Molecular Biology and Evolution (2008)

Crucifers (Brassicaceae, Cruciferae) are a large family comprising some 338 genera and c. 3,700 species. The family includes important crops as well as several model species in various fields of plant research. This paper reports new genome size (GS) data for more than 100 cruciferous species in addition to previously published C-values (the DNA amount in the unreplicated gametic nuclei) to give a data set comprising 185 Brassicaceae taxa, including all but 1 of the 25 tribes currently recognized. Evolution of GS was analyzed within a phylogenetic framework based on gene trees built from five data sets (matK, chs, adh, trnLF, and ITS). Despite the 16.2-fold variation across the family, most Brassicaceae species are characterized by very small genomes with a mean 1C-value of 0.63 pg. The ancestral genome size (ancGS) for Brassicaceae was reconstructed as anc1C = 0.50 pg. Approximately 50% of crucifer taxa analyzed showed a decrease in GS compared with the ancGS. The remaining species showed an increase in GS although this was generally moderate, with significant increases in C-value found only in the tribes Anchonieae and Physarieae. Using statistical approaches to analyze GS, evolutionary gains or losses in GS were seen to have accumulated disproportionately faster within longer branches. However, we also found that GS has not changed substantially through time and most likely evolves passively (i.e., a tempo that cannot be distinguished between neutral evolution and weak forms of selection). The data reveal an apparent paradox between the narrow range of small GSs over long evolutionary time periods despite evidence of dynamic genomic processes that have the potential to lead to genome obesity (e.g., transposable element amplification and polyploidy). To resolve this, it is suggested that mechanisms to suppress amplification and to eliminate amplified DNA must be active in Brassicaceae although their control and mode of operation are still poorly understood.
2009 Influenza A(H1N1) Seroconversion Rates and Risk Factors Among Distinct Adult Cohorts in Singapore
Authors: Mark I. C. Chen
Journal: JAMA (2010)

Singapore experienced a single epidemic wave of 2009 influenza A(H1N1) with epidemic activity starting in late June 2009 and peaking in early August before subsiding within a month.To compare the risk and factors associated with H1N1 seroconversion in different adult cohorts.A study with serial serological samples from 4 distinct cohorts: general population (n = 838), military personnel (n = 1213), staff from an acute care hospital (n = 558), and staff as well as residents from long-term care facilities (n = 300) from June 22, 2009, to October 15, 2009. Hemagglutination inhibition results of serum samples taken before, during, and after the epidemic and data from symptom questionnaires are presented.A 4-fold or greater increase in titer between any of the 3 serological samples was defined as evidence of H1N1 seroconversion.Baseline titers of 40 or more were observed in 22 members (2.6%; 95% confidence interval [CI], 1.7%-3.9%) of the community, 114 military personnel (9.4%; 95% CI, 7.9%-11.2%), 37 hospital staff (6.6%; 95% CI, 4.8%-9.0%), and 20 participants from long-term care facilities (6.7%; 95% CI, 4.4%-10.1%). In participants with 1 or more follow-up serum samples, 312 military personnel (29.4%; 95% CI, 26.8%-32.2%) seroconverted compared with 98 community members (13.5%; 95% CI, 11.2%-16.2%), 35 hospital staff (6.5%; 95% CI, 4.7%-8.9%), and only 3 long-term care participants (1.2%; 95% CI, 0.4%-3.5%). Increased frequency of seroconversion was observed for community participants from households in which 1 other member seroconverted (adjusted odds ratio [OR], 3.32; 95% CI, 1.50-7.33), whereas older age was associated with reduced odds of seroconversion (adjusted OR, 0.77 per 10 years; 95% CI, 0.64-0.93). Higher baseline titers were associated with decreased frequency of seroconversion in community (adjusted OR for every doubling of baseline titer, 0.48; 95% CI, 0.27-0.85), military (adjusted OR, 0.71; 95% CI, 0.61-0.81), and hospital staff cohorts (adjusted OR, 0.50; 95% CI, 0.26-0.93).Following the June-September 2009 wave of 2009 influenza A(H1N1), 13% of the community participants seroconverted, and most of the adult population likely remained susceptible.
Prehospital care for road traffic casualties
Authors: T J Coats
Journal: BMJ (2002)

For complex reasons, society seems to accept a lower standard of safety from road use compared with other forms of transport. Road traffic crashes cause some 320 000 injuries, 40 000 serious injuries, and 3400 deaths a year in the United Kingdom.1 This is equivalent to the Lockerbie air crash happening every four weeks or the Paddington rail crash happening every other day throughout the year. As road traffic crashes are so common, many doctors will give roadside treatment at some time during their career. A third of prehospital deaths may be preventable,2 so doctors have a duty to offer assistance at a crash scene, but this can be a frightening and distressing experience for those not trained to work in the prehospital environment.

#### Summary points

At some time in their career many doctors will have to deal with a road traffic crash

Safety for yourself at the incident scene is the first priority

Doctors untrained in prehospital care should concentrate on giving good first aid, working under the direction of ambulance service staff

Providing excellent medical treatment at a road crash requires specific training and experience

Patients with airway and breathing problems may need immediate (prehospital) advanced medical intervention

Treatment should be aimed at promoting oxygenation and preserving clot, with rapid patient movement to a hospital with the appropriate facilities to provide definitive care

This article was written from the authors' personal experience of working in prehospital care with the London Helicopter Emergency Medical Service, a review of articles in the Cochrane Library , a literature review, participation in internet discussion groups on prehospital care, and aggregated experience of colleagues from the Ambulance Service and the British Association of Immediate Care Schemes (BASICS).

This article is based on our synthesis of best practice, but there is often controversy about …
Restricted distribution of connexin40, a gap junctional protein, in mammalian heart.
Authors: D Gros, T Jarry-Guichard, I Ten Velde, A de Maziere, M J van Kempen, J Davoust, J P Briand, A F Moorman, H J Jongsma
Journal: Circulation Research (1994)

Connexin40 (Cx40) is a member of the connexin family of gap junction proteins. Its mRNA, abundant in lung, is also present in mammalian heart, although in lower amount. Rabbit antipeptide antibodies directed to the COOH terminus (residues 335 to 356) of rat Cx40 were characterized to investigate the distribution of Cx40 in rat and guinea pig cardiac tissues. The affinity-purified antibodies detect specifically a major protein (M(r), 40,000) in immunoblots of total extracts from rat lung and rat and guinea pig heart. In sections of guinea pig atrial tissue treated for immunofluorescence, a strong labeling associated with myocytes was seen with a distribution consistent with that of intercalated disks. The results of immunoelectron microscopy carried out with guinea pig atrial tissue showed that epitopes recognized by these antibodies were exclusively associated with gap junctions. These results, added to those of control experiments, demonstrate that antibodies 335-356 are specific for Cx40. Double-labeling experiments carried out with lung sections using anti-factor VIII and anti-Cx40 antibodies suggest that Cx40 is expressed in blood vessel endothelial cells. In guinea pig and rat heart sections, investigated using both immunofluorescence and immunoperoxidase techniques, a signal was also found to be associated with vascular walls. In guinea pig heart, only atrial myocytes are Cx40-positive. No labeling was detected in ventricular myocytes, including those of the His bundle and the bundle branches, which otherwise do express connexin43 (Cx43). In rat heart Cx40-expressing myocytes are localized in branches, and the Purkinje fibers. Cx43 is not detected either in the His bundle or in the proximal parts of the bundle branches, and consequently, Cx40 is the first connexin demonstrated in this region of the rat conduction system. Cx40 was not detected in the working ventricular myocytes. Double-labeling experiments carried out with hen anti-Cx43 antibodies and rabbit anti-Cx40 antibodies demonstrated that, in tissues expressing both Cx43 and Cx40, these two connexins were localized in the same immunoreactive sites. A few sites, however, appear to contain only one or the other of these two connexins.
Justice at Last
Authors: J. S. Bailey
Journal: BMJ (1966)

This study was designed to evaluate the pathologic criteria used for acute renal allograft rejection that were developed by a panel of renal pathologists participating in the Cooperative Clinical Trials in Transplantation, a National Institutes of Health-supported, multicenter research group. The panel defined three categories of acute rejection. (1) Type I: mononuclear infiltrate in &gt; or =5% of cortex, a total of at least three tubules with tubulitis in 10 consecutive high-power fields from the most severely affected areas, and at least two of the three following features: edema, activated lymphocytes, or tubular injury. (2) Type II: arterial, or arteriolar, endothelialitis with or without the preceding features. (3) Type III: arterial fibrinoid necrosis or transmural inflammation with or without thrombosis, parenchymal necrosis, or hemorrhage. Using these criteria, and without any knowledge of the clinical course or original diagnosis, a rotating panel of three pathologists agreed with the original study pathologist9s diagnosis of the presence or absence of rejection in 259 of the 286 biopsies (91%) used for this analysis (kappa = 0.80). The sensitivity to establish the diagnosis of rejection was 91% for a single core and 99% for two cores. To validate the diagnostic criteria, the thresholds for number of tubules with tubulitis and the percent infiltrate were varied, and the pathologic diagnosis was compared with the clinical course. The greatest agreement occurred with a threshold of &gt; or =1 tubule with tubulitis and &gt; or =5% cortex with interstitial infiltrate (91%). Clinically severe rejection episodes were correlated with the type of rejection (type I, odds ratio [OR] 6.2; type II, OR 37.9). Type II rejection was more likely to be clinically severe than type I (OR 6.1). Analysis of other individual pathologic features revealed a correlation with clinical severity for endothelialitis (OR 13.2), interstitial hemorrhage (OR 13.2), and the presence of glomerulitis (OR 3.7) (all P &lt; 0.05). The extent of tubulitis or of the interstitial infiltrate did not correlate with severity (P &gt; 0.05). It is concluded that these criteria are simple, reproducible, and clinically relevant. These data should lead to further refinement of the diagnostic systems for renal allograft rejection.
Development of multiple organ-localized autoimmune diseases in nude mice after reconstitution of T cell function by rat fetal thymus graft.
Authors: O Taguchi, T Takahashi, M Seto, R Namikawa, M Matsuyama, Y Nishizuka
Journal: The Journal of Experimental Medicine (1986)

Restoration of T cell function of athymic BALB/c nu/nu mice was investigated after transplantation of xenogeneic thymic rudiments from 15-d-old embryonic rats into kidney subcapsule. The rudiments developed well and formed a proper thymus structure composed of donor epithelia and host lymphocytes. Examination of antibody responses to SRBC revealed that approximately half the normal number of indirect PFCs were observed. Skin grafts from syngeneic BALB/c mice and thymic donor rat strains were accepted, whereas those from allogeneic mice and the rats of other than donor strains were vigorously rejected. Thymus-grafted nude mice under a conventional environment survived without any evident infectious diseases. Histological and immunofluorescence studies, however, showed a high incidence of multiple organ-localized autoimmune diseases in thyroid, salivary gland, stomach, adrenal, prostate, ovary, and testis in mice that produced the corresponding autoantibodies. These results together suggested that rat thymic grafts reconstituted T cell functions of nu/nu mice to a considerable degree, but that organ-localized autoimmune diseases developed, probably because certain auto-antigens of the recipients were recognized by the newly reconstituted host immunity.
Changes in Tumor Metabolism as Readout for Mammalian Target of Rapamycin Kinase Inhibition by Rapamycin in Glioblastoma
Authors: Liu Hua Wei, Helen Su, Isabel J. Hildebrandt, Michael E. Phelps, Johannes Czernin, Wolfgang A. Weber
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Inhibition of the protein kinase mammalian target of rapamycin (mTOR) is being evaluated for treatment of a variety of malignancies. However, the effects of mTOR inhibitors are cytostatic and standard size criteria do not reliably identify responding tumors. The aim of this study was to evaluate whether response to mTOR inhibition could be assessed by positron emission tomography (PET) imaging of tumor metabolism. Experiment Design: Glucose, thymidine, and amino acid utilization of human glioma cell lines with varying degrees of sensitivity to mTOR inhibition were assessed by measuring in vitro uptake of [18F]fluorodeoxyglucose ([18F]FDG), [18F]fluorothymidine ([18F]FLT), and [3H]l-tyrosine before and after treatment with the mTOR inhibitor rapamycin. The tumor metabolic activity in vivo was monitored by small-animal PET of tumor-bearing mice. The mechanisms underlying changes in metabolic activity were analyzed by measuring expression and functional activity of enzymes and transporters involved in the uptake of the studied imaging probes. Results: In sensitive cell lines, rapamycin decreased [18F]FDG and [18F]FLT uptake by up to 65% within 24 hours after the start of therapy. This was associated with inhibition of hexokinase and thymidine kinase 1. In contrast, [3H]l-tyrosine uptake was unaffected by rapamycin. The effects of rapamycin on glucose and thymidine metabolism could be imaged noninvasively by PET. In sensitive tumors, [18F]FDG and [18F]FLT uptake decreased within 48 hours by 56 ± 6% and 52 ± 8%, respectively, whereas there was no change in rapamycin-resistant tumors. Conclusions: These encouraging preclinical data warrant clinical trials evaluating [18F]FDG and [18F]FLT-PET for monitoring treatment with mTOR inhibitors in patients.
An improved technique for culture of catheter tips from open-heart surgery patients
Authors: R Freeman, N Hjersing
Journal: Thorax (1982)

Bacteria were isolated from 19·6% of left atrial catheter tips from open-heart surgical patients when incubation of the culture was prolonged to eight days and the prophylactic antibiotic given to the patient (flucloxacillin) was specifically neutralised with beta-lactamase. This compares with the previous estimate of 9·9% when a standard culture method was employed. Additionally, diphtheroid organisms were recovered from left atrial catheter tips using this new technique.
Tumor Microenvironment of Metastasis and Risk of Distant Metastasis of Breast Cancer
Authors: Thomas E. Rohan, Xiaonan Xue, Hung-Mo Lin, Timothy M. D’Alfonso, Paula S. Ginter, Maja H. Oktay, Brian D. Robinson, Mindy Ginsberg, Frank B. Gertler, Andrew G. Glass, Joseph A. Sparano, John S. Condeelis, Joan G. Jones
Journal: JNCI Journal of the National Cancer Institute (2014)

Tumor microenvironment of metastasis (TMEM), consisting of direct contact between a macrophage, an endothelial cell, and a tumor cell, has been associated with metastasis in both rodent mammary tumors and human breast cancer. We prospectively examined the association between TMEM score and risk of distant metastasis and compared risk associated with TMEM score with that associated with IHC4. We conducted a case–control study nested within a cohort of 3760 patients with invasive ductal breast carcinoma diagnosed between 1980 and 2000 and followed through 2010. Case patients were women who developed a subsequent distant metastasis; control subjects were matched (1:1) on age at and calendar year of primary diagnosis. TMEM was assessed by triple immunostain and IHC4 by standard methods; slides were read by pathologists blinded to outcome. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusted for clinical variables. A Receiver Operating Characteristic analysis was performed, and the area under the curve was estimated. All statistical tests were two-sided. TMEM score was associated with increased risk of distant metastasis in estrogen receptor (ER)+/human epidermal growth factor receptor (HER2)− tumors (multivariable OR high vs low tertile = 2.70; 95% CI = 1.39 to 5.26; Ptrend = .004), whereas IHC4 score had a borderline positive association (OR10 unit increase = 1.06; 95% CI = 1.00 to 1.13); the association for TMEM score persisted after adjustment for IHC4 score. The area under the curve for TMEM, adjusted for clinical variables, was 0.78. Neither TMEM score nor IHC4 score was independently associated with metastatic risk overall or in the triple negative or HER2+ subgroups. TMEM score predicted risk of distant metastasis in ER+/HER2− breast cancer independently of IHC4 score and classical clinicopathologic features.