tbuckley/cabot-search huggingface dataset:
Clinical relevance of Mycobacterium malmoense isolation in the Netherlands
Authors: W. Hoefsloot, J. van Ingen, W. C. M. de Lange, P. N. R. Dekhuijzen, M. J. Boeree, D. van Soolingen
Journal: European Respiratory Journal (2009)

Uncertainty exists about the clinical relevance of Mycobacterium malmoense isolation, especially in pulmonary samples. We therefore determined clinical relevance, treatment and outcome of M. malmoense isolation in The Netherlands. A retrospective medical file study was conducted for all patients in The Netherlands from whom Mycobacterium malmoense had been isolated between January 2002 and January 2006. Diagnostic criteria for nontuberculous mycobacterial (NTM) disease published by the American Thoracic Society (ATS) were used to determine clinical relevance. Treatment was compared with guidelines published by the British Thoracic Society. In total, 51 patients were found from whom M. malmoense was isolated. Of these, 40 (78%) patients had pulmonary isolates and 32 (80%) of them met the ATS diagnostic criteria. Cavitary disease was most common (n = 28; 88%). Patients with pulmonary disease were mostly males, with an average age of 56 yrs and pre-existing chronic obstructive pulmonary disease. Cervical lymphadenitis was the most common extrapulmonary disease type. Adherence to treatment guidelines was poor. A good clinical response to treatment was observed in 70% and 73% of patients treated for pulmonary and extrapulmonary disease, respectively. In conclusion, M. malmoense is a clinically highly relevant NTM in The Netherlands causing serious pulmonary morbidity. Adherence to treatment guidelines is not satisfactory.
Immunoelectron microscopic study of the distribution of T cell subsets in rheumatoid synovium.
Authors: M Kurosaka, M Ziff
Journal: The Journal of Experimental Medicine (1983)

The perivascular mononuclear cell collections of the rheumatoid synovium were examined both at the light and electron microscopic level by an immunoperoxidase staining technique using monoclonal antibodies directed against T cell subsets. These accumulations were variable in composition and size, not only in specimens from different patients but in the same specimen. Some areas (lymphocyte-rich areas) contained mainly small lymphocytes in clusters and others (transitional areas) contained blast cells, macrophages, and plasma cells in addition to lymphocytes. The percentage of T4 staining cells correlated positively and the percentage of T8 staining cells correlated negatively with the percentage of lymphocytes in any given area. In contrast, the percentage of T4 cells correlated negatively and the percentage of T8 cells correlated positively with the percentage of macrophage-like cells in these areas. Approximately 80% of the total lymphocytes, both in the lymphocyte-rich areas and transitional areas, were T lymphocytes (OKT3 staining). In lymphocyte-rich areas, helper/inducer T lymphocytes (OKT4 staining) were predominent over suppressor/cytotoxic lymphocytes (OKT8 staining), and in such areas the mean T4:T8 ratio was 2.9. Macrophage-like cells were seen only in small numbers in this type of area. In the transitional areas, suppressor/cytotoxic lymphocytes (OKT8 staining) predominated over helper/inducer lymphocytes (OKT4 staining). In such areas the mean T4:T8 ratio was 0.8. The T8 cells in the transitional areas tended to be large in size and often had a blastic appearance, and the abundant macrophage-like cells infiltrating these areas were frequently in close contact with T8 lymphocytes. These findings indicate that the ratio of T4 to T8 lymphocytes in rheumatoid synovium varies with the type of area examined. In lymphocyte-rich collections, made up largely of quiescent small lymphocytes, T4 cells are predominant. In areas of apparent immunological reactivity, T8 cells are predominant. It is suggested that T8 cells proliferate in immunologically active areas of the synovium as a result of local stimulation of a T cell-mediated immune response.
Concentration and reactivity of the sulphydryl group population on the membrane of intact erythrocytes in patients with rheumatoid arthritis.
Authors: C Chilles, M Mulheron, F M McCrae, J Reglinksi, W E Smith, M Brzeski, R D Sturrock
Journal: Annals of the Rheumatic Diseases (1990)

The sulphydryl population on erythrocyte membrane is shown to vary as a function of the nutritional status of the cell. When an assay based on reaction with Ellman's reagent and controlled conditions were used the mean values (SEM) for the sulphydryl population on the membranes of normal erythrocytes incubated overnight in the presence and absence of glucose were found to be 3.29 (0.27) and 2.56 (0.25) million sulphydryl functions per cell respectively. Under identical conditions rheumatoid erythrocytes incubated in the presence and absence of glucose were found to have a significantly lower sulphydryl population--1.54 (0.08) and 1.15 (0.08) million respectively. The predominant concentrations of sulphydryl groups on the membrane are found at sites on the transmembrane proteins and, in particular, on the hexose transport protein. By influencing the nutritional status of the cells significant differences in activity between the normal and diseased state have been identified and these may have a role in the aetiology of rheumatoid arthritis by altering the response of cells to oxidative stress.
Sensitivity of Surveillance Studies for Detecting Asymptomatic and Unsuspected Relapse of High-Risk Neuroblastoma
Authors: Brian H. Kushner, Kim Kramer, Shakeel Modak, Nai-KongV. Cheung
Journal: Journal of Clinical Oncology (2009)

Relapse-free survival (RFS) is a powerful measure of treatment efficacy. We describe the sensitivity of standard surveillance studies for detecting relapse of neuroblastoma (NB).The patients were in complete/very good partial remission of high-risk NB; routine monitoring revealed asymptomatic and, therefore, unsuspected relapses in 113 patients, whereas 41 patients had symptoms prompting urgent evaluations. Assessments every 2 to 4 months included computed tomography, iodine-131-metaiodobenzylguanidine (131)I-MIBG; through November 1999) or iodine-123-metaiodobenzylguanidine ((123)I-MIBG) scan, urine catecholamines, and bone marrow (BM) histology. Bone scan was routine through 2002.(123)I-MIBG scan was the most reliable study for revealing unsuspected relapse; it had an 82% detection rate, which was superior to the rates with (131)I-MIBG scan (64%; P = .1), bone scan (36%; P < .001), and BM histology (34%; P < .001). Among asymptomatic patients, (123)I-MIBG scan was the sole positive study indicating relapse in 25 (27%) of 91 patients compared with one (4.5%) of 22 patients for (131)I-MIBG scan (P = .04) and 0% to 6% of patients for each of the other studies (P < .001). Patients whose monitoring included (123)I-MIBG scan were significantly less likely than patients monitored by (131)I-MIBG scan to have an extensive osteomedullary relapse and had a significantly longer survival from relapse (P < .001) and from diagnosis (P = .002). They also had significantly longer survival than patients with symptomatic relapses (P = .002).(123)I-MIBG scan is essential for valid estimation of the duration of RFS of patients with high-risk NB. Without monitoring that includes (123)I-MIBG scan, caution should be used when comparing RFS between institutions and protocols.
Spontaneous remission of marginal zone B cell lymphoma in a patient with seropositive rheumatoid arthritis after discontinuation of infliximab-methotrexate treatment
Authors: R Thonhofer
Journal: Annals of the Rheumatic Diseases (2005)

We cannot, however, rule out the possibility that an association with other SNPs exists in these genes.Furthermore, we also acknowledge that because our sample size is limited we are unlikely to detect small differences in allele frequencies.
NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs
Authors: Christophe Borg, Abdelali Jalil, Diego Laderach, Kouji Maruyama, Hiro Wakasugi, Sabine Charrier, Bernhard Ryffel, Alessandra Cambi, Carl Figdor, William Vainchenker, Anne Galy, Anne Caignard, Laurence Zitvogel
Journal: Blood (2004)
Mapping Pathways From Stress to Cancer Progression
Authors: Karen Ross
Journal: JNCI Journal of the National Cancer Institute (2008)

Using in vitro, animal, and human clinical approaches, researchers are beginning to understand the relationship between psychological stress and cancer progression at the biochemical and molecular levels. The focus of many of these studies is basic biology — the experience of stress and changes in gene expression that may be associated with tumor progression. “We’re very much interested in taking an incremental approach and elucidating potential biological processes that might be involved,” said Paige McDonald, Ph.D., chief of the National Cancer Institute’s Basic and Biobehavioral Research Branch, which funds research on stress and cancer. “Our goal is to support very sophisticated mechanistic studies, with the eventual goal of using those basic science data to develop effective interventions.” Earlier studies on stress and cancer often looked for associations between
Experts question usefulness of screening travellers to UK for Ebola
Authors: A. Gulland
Journal: BMJ (2014)

Experts have questioned the effectiveness of the UK government’s announcement that it is going to introduce screening at major UK transport terminals in a bid to intercept travellers with Ebola disease.

The government made the announcement to stem fears over the potential spread of the disease in the United Kingdom, after a man in the United States died from the disease and a nurse caring for missionaries with the disease in Spain became infected.1 2 3 The US has also introduced screening at five major airports.4

Enhanced screening will initially be implemented at Heathrow and Gatwick airports and the Eurostar train terminals and will be conducted by medical rather than border force staff, the spokesman added.

Only travellers from the three affected countries—Sierra Leone, Liberia, and Guinea—will …
ANTIBODY FORMATION BY SINGLE CELLS FROM LYMPH NODES AND EFFERENT LYMPH OF SHEEP
Authors: A. J. Cunningham, J. B. Smith, E. H. Mercer
Journal: The Journal of Experimental Medicine (1966)

The antibody-forming cells which appear in the popliteal lymph node and efferent lymph of the sheep following immunization with boiled Salmonella have been studied by light and electron microscopy. Cells were incubated in monolayers with target erythrocytes sensitized with bacterial lipopolysaccharide. Three types of interaction between a proportion of the lymph cells and the erythrocytes surrounding them have been shown to indicate antibody formation: plaque-formation, immuno-cyto-adherence, and localized agglutination. At the peak of the response, 4 days after antigenic stimulation approximately 1 cell in every 200 from lymph node suspensions produces detectable specific antibody, while up to 1 cell in 20 in the lymph is active. For light microscope examination, individual antibody-forming cells were smeared in serum and stained with Leishman's stain. For electron microscopy, a number of active cells were clumped with antiserum to form a specimen of convenient size, then sectioned. Most of the active cells from efferent lymph are large and basophilic, while a small proportion are blastlike. These cells contain abundant free ribosomes and very little endoplasmic reticulum. In the node only, an additional class of antibody-forming plasma cells is found which have considerable amounts of endoplasmic reticulum in their cytoplasm.
Functional TauT Protects Against Acute Kidney Injury
Authors: Xiaobin Han, Junming Yue, Russell W. Chesney
Journal: Journal of the American Society of Nephrology (2009)

Nephrotoxicity is common with the use of the chemotherapeutic agent cisplatin, but the cellular mechanisms that modulate the extent of injury are unknown. Cisplatin downregulates expression of the taurine transporter gene (TauT) in LLC-PK1 proximal tubular renal cells, and forced overexpression of TauT protects against cisplatin-induced apoptosis in vitro. Because the S3 segments of proximal tubules are the sites of both cisplatin-induced injury and adaptive regulation of the taurine transporter, we hypothesized that TauT functions as an anti-apoptotic gene and protects renal cells from cisplatin-induced nephrotoxicity in vivo. Here, we studied the regulation of TauT in cisplatin nephrotoxicity in a human embryonic kidney cell line and in LLC-PK1 cells, as well as in TauT transgenic mice. Cisplatin-induced activation of p53 repressed TauT and overexpression of TauT prevented the progression of cisplatin-induced apoptosis and renal dysfunction in TauT transgenic mice. Although cisplatin activated p53 and PUMA (a p53-responsive proapoptotic Bcl-2 family protein) in the kidneys of both wildtype and TauT transgenic mice, only wildtype animals demonstrated acute kidney injury. These data suggest that functional TauT plays a critical role in protecting against cisplatin-induced nephrotoxicity, possibly by attenuating a p53-dependent pathway.
The value of amino-terminal propeptide of type III procollagen in routine screening for methotrexate-induced liver fibrosis: a 10-year follow-up
Authors: H. Zachariae, L. Heickendorff, H. Søgaard
Journal: British Journal of Dermatology (2001)

Methotrexate (MTX) -induced liver damage is an important complication in patients treated with this drug for skin disease. Reliable non-invasive monitoring tests would have considerable importance.This retrospective study was designed in order to evaluate if serial normal serum levels of amino-terminal propeptide of type III procollagen (PIIINP) might indicate that no significant fibrosis is taking place in the liver, and thereby reduce the need for repeated liver biopsies in psoriatic patients treated with MTX.The clinical records of 70 patients with psoriasis, who in the years 1989/90 were on MTX and had both a liver biopsy without fibrosis and a normal PIIINP, were examined and followed until the patient stopped taking the drug. The follow-up time was from 1 to 11 years.A total of 189 liver biopsies and 329 analyses of PIIINP were recorded. Twenty-one patients had only one and no further biopsies, but their data included at least two to three PIIINP samples obtained within a year around the time of the biopsy, and at least two were taken either prior to or at the time of the biopsy. The remaining patients had from two to seven liver biopsies each and a total of 267 analyses of PIIINP. In the study period only four patients developed fibrosis of the liver as shown by liver biopsies, and all four of these patients developed elevated serum PIIINP levels. In addition two further patients, one of them with psoriatic arthritis, had elevated PIIINP, but normal liver biopsy. Thus no liver fibrosis was missed in the 63 patients with consistently normal PIIINP levels.Present data support the view that, as long as PIIINP is consistently normal in serial investigations, there is minimal risk of development of substantial liver fibrosis.
Renal Effects of Angiotensin II Infusions in Normotensive Pregnant and Nonpregnant Women
Authors: LEON C. CHESLEY, RALPH M. WYNN, NEIL I. SILVERMAN
Journal: Circulation Research (1963)

Normotensive pregnant women are relatively resistant to angiotensin II in that they give smaller pressor responses and show smaller reductions in urine flow and sodium and chloride excretions than do normotensive nonpregnant women. Women early in the third trimester of pregnancy are more resistant to angiotensin II than are women at term, with respect to the effect upon sodium and chloride excretions. The less pronounced renal effects of angiotensin II in pregnant women cannot be attributed merely to error caused by increase in the dead space of the urinary tract.
Junior doctors conference Juniors want to be included in working time directive HIV should not be barrier to medical school Public health doctors look to the future Second wave of health action zones launched
Authors: Linda Beecham
Journal: BMJ (1998)

# Junior doctors conference {#article-title-2}

“Regional task forces will continue and will be funded until we have met the new deal targets.” This was the promise that the health minister, Mr Alan Milburn, gave the BMA's junior doctors conference earlier this month.

Irrespective of contracted hours no junior doctor should be expected to work for more than 56 hours a week. This target was set for 31 December 1996, but the minister admitted that at March 1998, almost 17% of junior posts did not comply with the new deal. Although the deal had brought significant reductions in hours of work and work intensity, he said that the non-compliance in a few places was unacceptable. “I expect local employers to progress,” Mr Milburn said.

Improving standards of accommodation for doctors on call and out of hours catering were also parts of the deal, and the minister has already told human resource managers in the NHS that these were two of his key priorities. But he was not prepared to leave things to chance. “In future,” he said, “all NHS trusts will have their performance in this area properly monitored and the government will expect to see clear evidence of progress against proper tough targets.” Referring to the Junior Doctors Committee's charter on catering standards (9 May, p 1465), Mr Milburn told the conference that he has asked his officials to work with the JDC and NHS employers to reach some common agreement on what doctors can expect and what trusts can deliver.

### Extra doctors to be considered

On education and training, the minister said that the government was committed to offering junior doctors the best possible programme of service experience and educational activities. It was “actively considering” the proposal from the Medical Workforce Standing Advisory Committee (the Campbell committee) to increase the number of doctors in training by 1000. There would …
Impact of Long-Term Serum Platinum Concentrations on Neuro- and Ototoxicity in Cisplatin-Treated Survivors of Testicular Cancer
Authors: Mette Sprauten, Thomas H. Darrah, Derick R. Peterson, M. Ellen Campbell, Robyn E. Hannigan, Milada Cvancarova, Clair Beard, Hege S. Haugnes, Sophie D. Fosså, Jan Oldenburg, Lois B. Travis
Journal: Journal of Clinical Oncology (2011)

Cisplatin-induced neurotoxicity and ototoxicity (NTX) are important adverse effects after chemotherapy for testicular cancer (TC). Although serum platinum is measurable years after therapy, its impact on NTX has not been evaluated.In all, 169 cisplatin-treated survivors of TC provided blood samples at Survey I and reported NTX during Survey I (1998-2002) and Survey II (2007-2008). Serum platinum was quantified by inductively coupled plasma mass spectrometry. Patient-reported outcomes were evaluated with the Scale for Chemotherapy-Induced Neurotoxicity (SCIN), regarding the extent of symptom bother as 0, "not at all"; 1, "a little"; 2, "quite a bit"; or 3, "very much." Summing the six symptom scores yielded a total SCIN score of 0 to 18. Categorizing total SCIN scores into quartiles yielded similar-sized groups with increasing symptoms. Multivariate ordinal logistic regression analyses evaluated associations between NTX and long-term serum platinum levels, adjusting for cisplatin dose, dosing schedule, and age.At Survey I, a significant four- to five-fold association with total SCIN score emerged for the highest serum platinum quartile (odds ratio [OR], 4.69; 95% CI, 1.82 to 12.08). Paresthesias and Raynaud's syndrome (hands and feet) showed significant two- to four-fold increased risks with the highest platinum quartile. At Survey II, total SCIN score remained significantly associated with the highest platinum quartile (OR, 4.28; 95% CI, 1.36 to 13.48). Paresthesias (hands and feet) and tinnitus showed significant three- to four-fold increased risks for the highest platinum quartile. Cumulative cisplatin dose was not associated with total SCIN score or individual SCIN symptoms in multivariate analyses.Here we document a significant relationship between increasing levels of residual serum platinum and NTX severity after adjusting for initial cisplatin dose.
Antiviral Protection and Germinal Center Formation, But Impaired B Cell Memory in the Absence of CD19
Authors: Thomas Fehr, Robert C. Rickert, Bernhard Odermatt, Jürgen Roes, Klaus Rajewsky, Hans Hengartner, Rolf M. Zinkernagel
Journal: The Journal of Experimental Medicine (1998)

Coligation of CD19, a molecule expressed during all stages of B cell development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complement receptor (CR)2. Generation and analysis of CD19 gene–targeted mice revealed that T cell–dependent (TD) antibody responses to proteinaceous antigens were impaired, whereas those to T cell–independent (TI) type 2 antigens were normal or even augmented. These results are compatible with earlier complement depletion studies and the postulated function of CD19. To analyze the role of CD19 in antiviral antibody responses, we immunized CD19−/− mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI responses was more dependent on antigen dose and replicative capacity than on antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal transducer for complement. In contrast to immunization with protein antigens, infection of CD19−/− mice with replicating virus led to generation of specific germinal centers, which persisted for &amp;gt;100 d, whereas maintenance of memory antibody titers as well as circulating memory B cells was fully dependent on CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under limiting antigen conditions and indicates an important role for B cell memory.
The Impact of Genomics-Based Technologies on Drug Safety Evaluation
Authors: Jeffrey F. Waring, Roger G. Ulrich
Journal: The Annual Review of Pharmacology and Toxicology (2000)

Determining the potential toxicity of compounds early in the drug discovery process can be extremely beneficial in terms of both time and money conservation. Because of the speed of modern chemical synthesis and screening, to accurately evaluate the large number of compounds being produced, toxicology assays must have both high-fidelity and high-throughput capabilities. In addition, assays must be performed using limited amounts of compound. In the past decade, several new and innovative techniques have been developed that not only allow for high-throughput screening but can also provide detailed information concerning the molecular mechanisms behind toxic effects. Techniques such as hybridization microarrays, real-time polymerase chain reaction, and large-scale sequencing are some of the methods that have been or are starting to be used routinely in pharmaceutical companies. This review examines the contributions of these and related techniques toward toxicity evaluation of potential drug candidates and their future role in the discovery of new therapeutics.