tbuckley/cabot-search huggingface dataset:
Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones.
Authors: H Gascan, J F Gauchat, M G Roncarolo, H Yssel, H Spits, J E de Vries
Journal: The Journal of Experimental Medicine (1991)

In the present study, it is demonstrated that cloned surface IgM-positive human B cells can be induced to proliferate and to switch with high frequencies to IgG4 and IgE production after a contact-mediated signal provided by T cell clones and interleukin 4 (IL-4). This T cell signal is antigen nonspecific and is provided by activated CD4+ cells, whereas activated CD8+ or resting CD4+ T cell clones are ineffective. 15-35% of the B cell clones cultured with cloned CD4+ T cells and IL-4 produced antibodies; 35-45% of those wells in which antibodies were produced contained IgE and IgG4. In addition to B cell clones that produced IgG4 or IgE only, B cell clones producing multiple isotypes were observed. Simultaneous production of IgG4 and IgE, IgM, IgE, and IgM, or IgG4 and IgE was detected, suggesting that during clonal expansion switching might occur in successive steps from IgM to IgG4 and IgE. In addition, production of only IgM, IgG4, and IgE during clonal expansion indicates that this isotype switching is directed by the way a B cell is stimulated and that it is not a stochastic process.
Hear my song: auditory hallucinations with tramadol hydrochloride
Authors: P. W Keeley, G. Foster, L. Whitelaw
Journal: BMJ (2000)

Tramadol hydrochloride is a weak opioid with effects on seratoninergic and adrenergic neurotransmission.1 It is reported to have fewer opioid adverse effects than conventional opioid analgesia.2 We report an unusual but important adverse effect not previously reported with the drug.

A 74 year old man with lung cancer was referred to the palliative care team for symptom control. He had pain in the left side of his chest and was advised to take tramadol hydrochloride 50 mg four times daily at home. Soon after starting the tramadol, he …
Cartilage in children's lungs: a quantitative assessment using the right middle lobe.
Authors: C C Sinclair-Smith, J L Emery, D Gadsdon, F Dinsdale, J Baddeley
Journal: Thorax (1976)

<b>Jones, A. W. and Madda, P. J. (1974).</b><i>Thorax</i>, <b>29</b>, 195-198. <b>Necropsy incidence of emphysema in Uganda.</b> The incidence and types of pulmonary emphysema and the degree of dust pigmentation of the lungs were investigated in a series of 183 necropsies in Uganda. Emphysema was present in 43 (23·5%) lungs. Panlobular or centrilobular emphysema was found in 17 cases, an overall incidence of 9·3% (10·4% of the 135 males and 6·3% of the 48 females). It was generally of mild degree and the mean lung involvement, as assessed by a point counting method, was 9·2% in the 17 cases described above. Panlobular and centrilobular emphysema occurred in the older age groups; 13 of the 17 cases were 50 years old or more. The remaining 26 cases consisted of irregular (scar) emphysema which occurred in trace amounts (less than 1%). Dust pigmentation was present in all 17 cases of emphysematous lungs and was generally more severe than in the non-emphysematous lungs. The incidence of emphysema in this predominantly rural population is low and is similar to that found in Ibadan, Nigeria.
Irradiation-related ischemic heart disease.
Authors: B W Corn, B J Trock, R L Goodman
Journal: Journal of Clinical Oncology (1990)

An expectation for long-term survival has emerged among several groups of cancer patients treated with therapeutic irradiation (eg, Hodgkin's disease, early stage breast cancer). Therefore, the cardiovascular sequelae of thoracic irradiation have recently come under scrutiny. Animal models have demonstrated that cardiac irradiation can directly damage the myocardial microvasculature and can indirectly damage the coronary macrovasculature when coupled with cholesterol feeding. A clear association between thoracic radiotherapy and ischemic heart disease was observed among older clinical studies using radiotherapeutic techniques that are no longer optimal by today's standards. Such a relationship could not be confirmed in modern studies in which treatment factors (such as dose and volume of heart irradiated) were more carefully controlled.
Placental/umbilical cord blood for unrelated-donor bone marrow reconstitution: relevance of nucleated red blood cells
Authors: Cladd E. Stevens, Jessica Gladstone, Patricia E. Taylor, Andromachi Scaradavou, Anna Rita Migliaccio, Jan Visser, N. Ludy Dobrila, Carmelita Carrier, Michael Cabbad, Peter Wernet, Joanne Kurtzberg, Pablo Rubinstein
Journal: Blood (2002)
Cyclin B1 Is a Critical Target of RhoB in the Cell Suicide Program Triggered by Farnesyl Transferase Inhibition
Authors: Uma Kamasani, Minzhou Huang, James B. DuHadaway, Edward V. Prochownik, P. Scott Donover, George C. Prendergast
Journal: Cancer Research (2004)

Abstract Farnesyl transferase inhibitors (FTIs) have displayed limited efficacy in clinical trials, possibly because of their relatively limited cytotoxic effects against most human cancer cells. Therefore, efforts to leverage the clinical utility of FTIs may benefit from learning how these agents elicit p53-independent apoptosis in mouse models of cancer. Knockout mouse studies have established that gain of the geranylgeranylated isoform of the small GTPase RhoB is essential for FTI to trigger apoptosis. Here we demonstrate that Cyclin B1 is a crucial target for suppression by RhoB in this death program. Steady-state levels of Cyclin B1 and its associated kinase Cdk1 were suppressed in a RhoB-dependent manner in cells fated to undergo FTI-induced apoptosis. These events were not derivative of cell cycle arrest, because they did not occur in cells fated to undergo FTI-induced growth inhibition. Mechanistic investigations indicated that RhoB mediated transcriptional suppression but also accumulation of Cyclin B1 in the cytosol at early times after FTI treatment, at a time before the subsequent reduction in steady-state protein levels. Enforcing Cyclin B1 expression attenuated apoptosis but not growth inhibition triggered by FTI. Moreover, enforcing Cyclin B1 abolished FTI antitumor activity in graft assays. These findings suggest that Cyclin B1 suppression is a critical step in the mechanism by which FTI triggers apoptosis and robust antitumor efficacy. Our findings suggest that Cyclin B1 suppression may predict favorable clinical responses to FTI, based on cytotoxic susceptibility, and they suggest a rational strategy to address FTI nonresponders by coinhibition of Cdk1 activity.
AIDS and the lung: update 1995. 1. Pneumocystis carinii pneumonia.
Authors: R F Miller, D M Mitchell
Journal: Thorax (1995)

Despite effective prophylaxis, Pneumocystis carinii pneumonia remains a common cause of respiratory disease in HIV infected patients.1Since the last update article in 19922 there have been further advances in our understanding of the molecular biology of this opportunistic fungus and there have been developments in the epidemiology, diagnosis, treatment, and prophylaxis of this infection.In this article we review recent advances in the molecular biology of P carinii and clinical aspects of management of HIV infected patients with pneumocystis pneumonia.
Hunting for the pathogenesis of rheumatoid arthritis: core-needle biopsy of inguinal lymph nodes as a new research tool
Authors: Maria J H de Hair, IJsbrand A J Zijlstra, Maria J H Boumans, Marleen G H van de Sande, Mario Maas, Danielle M Gerlag, Paul P Tak
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Abstract</h3> The explosive spread of the Omicron SARS-CoV-2 variant underscores the importance of analyzing the cross-protection from previous non-Omicron infection. We developed a high-throughput neutralization assay for Omicron SARS-CoV-2 by engineering the Omicron spike gene into an mNeonGreen USA-WA1/2020 SARS-CoV-2 (isolated in January 2020). Using this assay, we determined the neutralization titers of patient sera collected at 1- or 6-months after infection with non-Omicron SARS-CoV-2. From 1- to 6-month post-infection, the neutralization titers against USA-WA1/2020 decreased from 601 to 142 (a 4.2-fold reduction), while the neutralization titers against Omicron-spike SARS-CoV-2 remained low at 38 and 32, respectively. Thus, at 1- and 6-months after non-Omicron SARS-CoV-2 infection, the neutralization titers against Omicron were 15.8- and 4.4-fold lower than those against USA-WA1/2020, respectively. The low cross-neutralization against Omicron from previous non-Omicron infection supports vaccination of formerly infected individuals to mitigate the health impact of the ongoing Omicron surge.
Development of prognostic indicators using classification and regression trees for survival
Authors: Martha E. Nunn, Juanjuan Fan, Xiaogang Su, Richard A. Levine, Hyo‐Jung Lee, Michael K. McGuire
Journal: Periodontology 2000 (2011)

Abstract Development of an accurate prognosis is an integral component of treatment planning in the practice of periodontics. Prior work has evaluated the validity of using various clinical measured parameters for assigning periodontal prognosis as well as for predicting tooth survival and change in clinical conditions over time. We critically review the use of multivariate classification and regression trees (CART) for survival in developing evidence‐based periodontal prognostic indicators. We focus attention on two distinct methods for multivariate CART for survival: the marginal goodness‐of‐fit approach and the multivariate exponential approach. A number of common clinical measures have been found to be significantly associated with tooth loss from periodontal disease, including furcation involvement, probing depth, mobility, crown/root ratio and oral hygiene. However, the inter‐relationships among these measures, as well as the relevance of other clinical measures to tooth loss from periodontal disease (such as bruxism, family history of periodontal disease and overall bone loss), remain less clear. Although the inferences that can be drawn from any single study are necessarily limited, application of new approaches in epidemiological analyses to periodontal prognosis, such as CART for survival, should yield important insights into our understanding and treatment of periodontal diseases.
The Lack of Epithelial Interleukin-7 and BAFF/BLyS Gene Expression in Prostate Cancer as a Possible Mechanism of Tumor Escape from Immunosurveillance
Authors: Emma Di Carlo, Tommaso D'Antuono, Paolo Pompa, Rossella Giuliani, Sandra Rosini, Liborio Stuppia, Piero Musiani, Carlo Sorrentino
Journal: Clinical Cancer Research (2009)

The human prostate is endowed with intraepithelial and stromal lymphocytes, which may develop lymphoid follicles (LF) and allow a local immune response. We sought to investigate whether interleukin (IL)-7 and BAFF/BLyS, two fundamental survival factors for T and B cells, are expressed in the normal and neoplastic prostate and affect intraprostatic lymphocyte homeostasis.We have used real-time reverse transcription-PCR of microdissected prostatic glands and confocal microscopy to detect cytokine production, combined with immunohistochemistry to characterize intraprostatic lymphocytes.Prostatic epithelia constitutively produce IL-7 and, to a lesser extent, BAFF/BLyS. Indeed, we show that IL-7 receptor alpha is expressed by intraepithelial T lymphocytes and parafollicular T cells, whereas BAFF-R is found on periglandular B lymphocytes and mantle zone B cells of LFs. Prostate-homing B and T lymphocytes are scarcely proliferating, whereas most of them express the antiapoptotic protein bcl-2 and reveal a low apoptotic index in the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The transition from normal to neoplastic glands in prostate cancer (PCa) is marked by a dramatic decline of IL-7 and BAFF/BLyS production. Accordingly, PCa is characterized by a significant reduction of intraepithelial lymphocytes and loss of LFs. B-cell and T-cell expression of bcl-2 decrease, whereas the apoptotic events increase. The remaining PCa-infiltrating lymphocytes are mostly CD8(+) T cells that lack terminal differentiation and barely penetrate neoplastic glands.These results suggest that epithelial IL-7 and BAFF/BLyS production support intraprostatic lymphocyte survival. Its loss in PCa is associated with a severe depletion of prostate-associated lymphocytes and points to a novel tumor escape mechanism.
Misuses and Misunderstandings of Boundary Theory in Clinical and Regulatory Settings
Authors: Thomas G. Gutheil, Glen O. Gabbard
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: This paper outlines a number of misapplications of boundary theory in both regulatory settings and clinical situations. METHOD: The authors review clinical vignettes that illustrate the difference between boundary crossings, which lead to productive work in psychotherapy, and boundary violations, which are harmful to the patient and exploit the patient's vulnerable position. They also discuss developments in the field that have led to an excessively rigid and defensive posture on the part of some clinicians that may lead to less than optimal psychiatric treatment. They survey recent developments in the wording of state statutes that broadly define sexual misconduct in psychotherapy. RESULTS: This review of the current status of boundary theory in both the law and clinical practice suggests that an overreaction has occurred that requires correction. CONCLUSIONS: The critical role of context must be considered whenever a boundary problem has been alleged, and boundaries must be regarded as flexible standards of good practice rather than lists of generically forbidden behavior.
Interferon-α-2b and oral cytarabine ocfosfate for newly diagnosed chronic myeloid leukaemia
Authors: P. Mollee, C. Arthur, T. Hughes, H. Januszewicz, A. Grigg, K. Bradstock, M. Wolf, J. Gibson, A.P. Schwarer, A. Spencer, P. Browett, T. Hawkins, M. Seldon, R. Herrmann, A. Watson, J.F. Seymour, N. Martin, S. Shina, C. Low, S. Wright, R. Rodwell, J. Coulston, J. Morton, H. Blacklock, D. Taylor, K.M. Taylor
Journal: Annals of Oncology (2004)
Potentially reversible causes of non-ventricular fibrillation/ventricular tachycardia (VF/VT)
Authors: P D Macintyre, E L Lloyd
Journal: British Journal of Sports Medicine (2000)

A useful mnemonic derived from the conditions shown in fig 1 causing a non-VF/VT cardiac arrest is the four Hs and the four Ts.



 Figure 1  
Climbers in snowhole.  Figure 2  
Climber in spindrift. 



There are many cardiac and respiratory causes of severe hypoxia, which require emergency treatment of the underlying condition. Oxygen treatment in an appropriate dose should be administered where possible. However, it is important to exclude a mechanical cause such as upper airways obstruction or tension pneumothorax.

The casualty should be inspected for evidence of haematemesis or melaena stool. Internal haemorrhage should always be suspected with evidence of penetrating wounds to the abdomen or chest.

Elevated plasma potassium levels occur with renal failure, diabetic ketoacidosis, potassium sparing diuretics, or excessive ingestion of potassium salts. In the context of a cardiac arrest, the patient should be given intravenously 10 ml 10% …
Pre-Invasive Ovarian Mucinous Tumors Are Characterized by <i>CDKN2A</i> and <i>RAS</i> Pathway Aberrations
Authors: Sally M. Hunter, Kylie L. Gorringe, Michael Christie, Simone M. Rowley, David D. Bowtell, Ian G. Campbell
Journal: Clinical Cancer Research (2012)

Abstract Introduction: Mucinous tumors are the second most common form of epithelial ovarian tumor, yet the cell of origin for this histologic subtype remains undetermined. Although these tumors are thought to arise through a stepwise progression from benign cystadenoma to borderline tumor to invasive carcinoma, few studies have attempted to comprehensively characterize the genetic changes specific to this subtype or its precursors. Methods: To explore the spectrum of genomic alterations common to mucinous tumors we carried out high-resolution genome-wide copy number analysis, mutation screening by Sanger sequencing and immunohistochemistry on a series of primary ovarian mucinous cystadenomas (n = 20) and borderline tumors (n = 22). Results: Integration of copy number data, targeted mutation screening of RAS/RAF pathway members and immunohistochemistry reveals that p16 loss and RAS/RAF pathway alterations are highly recurrent events that occur early during mucinous tumor development. The frequency of concurrence of these events was observed in 40% of benign cystadenomas and 68% of borderline tumors. Conclusions: This study is the largest and highest resolution analysis of mucinous benign and borderline tumors carried out to date and provides strong support for these lesions being precursors of primary ovarian mucinous adenocarcinoma. The high level of uniformity in the molecular events underlying the pathogenesis of mucinous ovarian tumors provides an opportunity for treatments targeting specific mutations and pathways. Clin Cancer Res; 18(19); 5267–77. ©2012 AACR.
Redefining the Role of Public Health in Disability
Authors: Donald J. Lollar, John E. Crews
Journal: Annual Review of Public Health (2003)

▪ Abstract The stated mission of current public health activities is to prevent mortality, morbidity, and disability. Though this mission is a noble challenge, attention is now being drawn to that group of the public who are not prevented from living with a disability. This chapter seeks to redefine the functions of public health in the field of disability. It describes the changing demographics of disability and provides a framework for addressing the complex issues associated with defining disability. Finally, we outline a strategy for stronger and clearer public health presence to improve the health and well-being of people with disabilities.
High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Children and Adults With Newly Diagnosed Pineoblastomas
Authors: Sridharan Gururangan, Colleen McLaughlin, Jennifer Quinn, Jeremy Rich, David Reardon, Edward C. Halperin, James Herndon, Herbert Fuchs, Timothy George, James Provenzale, Melody Watral, Roger E. McLendon, Allan Friedman, Henry S. Friedman, Joanne Kurtzberg, James Vredenbergh, Paul L. Martin
Journal: Journal of Clinical Oncology (2003)

We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL).Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR.A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively.The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.
The microbial colonization of inflamed acne vulgaris lesions
Authors: J.P. LEEMING, K.T. HOLLAND, W.J. CUNCLIFFE
Journal: British Journal of Dermatology (1988)

Seventy one papules in the early stages of inflammatory development were isolated from acne vulgaris affected skin and their content of micro-organisms characterized. The progress of lesions prior to excision was monitored by tracing an area of the upper back onto a transparent acetate sheet. This template was used the next day, and in some cases after 3 days, to identify inflamed lesions of less than 1 day and 2–3 days duration. These were biopsied, and pilosebaceous units isolated by micro-dissection, homogenized and microbial populations studied by viable counting and microscopy. Propionibacteria colonised 68% of'1 day'duration lesions and 79% of'3 day'duration lesions; staphylococci colonized 19% and 32% respectively and Pityrosporum spp. (Malassezia furfur) were found in 52% and 68%. Although the prevalence of each microbial group was higher in the more chronic lesions, these differences were not statistically significant. The microbial profile of inflamed lesions was similar both qualitatively and quantitatively to non-inflamed lesions studied previously. These results call into question the role of micro-organisms as the initiators of inflammation in acne vulgaris.
Dual Channel Optical Tomographic Imaging of Leukocyte Recruitment and Protease Activity in the Healing Myocardial Infarct
Authors: Matthias Nahrendorf, David E. Sosnovik, Peter Waterman, Filip K. Swirski, Ashvin N. Pande, Elena Aikawa, Jose-Luiz Figueiredo, Mikael J. Pittet, Ralph Weissleder
Journal: Circulation Research (2007)

Inflammatory responses after myocardial infarction profoundly impact tissue repair. Yet, efficient tools to serially and noninvasively assess cellular and molecular functions in postinfarct inflammation are lacking. Here we use multichannel fluorescent molecular tomography (FMT) for spatiotemporal resolution of phagocytic and proteolytic activities mediated by macrophages and neutrophils in murine infarcts. We performed FMT imaging to compare the course of efficient and impaired healing in wild-type and FXIII-/- mice, respectively. Mice subjected to coronary ligation received simultaneous injections with Prosense-680, an activatable fluorescence sensor reporting on cathepsin activity, and CLIO-VT750, a magneto-fluorescent nanoparticle for imaging of phagocyte recruitment. On FMT, Prosense-680 infarct signal was 19-fold higher than background (P<0.05). Protease activity was higher in the infarcted lateral wall than in the remote, uninjured septum on ex vivo fluorescence reflectance imaging (contrast to noise ratio 118+/-24). CLIO-VT750 FMT signal coregistered with contrast enhancement in the hypokinetic infarct on MRI. Microscopic fluorescence signal colocalized with immunoreactive staining for cathepsin, macrophages and neutrophils. Flow cytometry of digested infarcts revealed monocytes/macrophages and neutrophils as the source of the fluorescence signal. Phagocytic activity peaked on day 6, and proteolytic activity peaked on day 4 after myocardial infarction. FMT detected impaired recruitment of phagocytes and protease activity in FXIII-/- mice (P<0.05). FMT is a promising noninvasive molecular imaging approach to characterize infarct healing. Spectrally resolved imaging agents allow for simultaneous assesment of key processes of in vivo cellular functions. Specifically, we show that in vivo FMT detects impaired healing in FXIII-/- mice.