tbuckley/cabot-search huggingface dataset:
Unilateral pulmonary collapse in asthmatics.
Authors: J A Hopkirk, J E Stark
Journal: Thorax (1978)

Five asthmatic patients developed collapse of one lung. Three of the patients were children and three of the five had repeated episodes of atelectasis. Episodes of atelectasis were usually associated with localised chest pain, which was not pleuritic in character, and with breathlessness, but without wheezing. The were not related to clinically apparent respiratory infections or to deterioration of the underlying asthma. The cause is obscure, but re-expansion seems to be hastened by oral corticosteroid therapy.
Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity.
Authors: F Powrie, R Correa-Oliveira, S Mauze, R L Coffman
Journal: The Journal of Experimental Medicine (1994)

BALB/c mice infected with the intracellular protozoan Leishmania major mount a T helper cell 2 (Th2) response that fails to control growth of the parasite and results in the development of visceral leishmaniasis. Separation of CD4+ T cells into CD45RBhigh and CD45RBlow subsets showed that the L. major-specific Th2 cells were contained within the CD45RBlow population as these cells produced high levels of antigen-specific interleukin 4 (IL-4) in vitro and transferred a nonhealing response to L. major-infected C.B-17 scid mice. In contrast, the CD45RBhighCD4+ population contained L. major-reactive cells that produced interferon gamma (IFN-gamma) in vitro and transferred a healing Th1 response to L. major-infected C.B-17 scid mice. Transfer of the Th1 response by the CD45RBhigh population was inhibited by the CD45RBlow population by a mechanism that was dependent on IL-4. These data indicate that L. major-specific Th1 cells do develop in BALB/c mice, but their functional expression is actively inhibited by production of IL-4 by Th2 cells. In this response, the suppressed Th1 cells can be phenotypically distinguished from the suppressive Th2 cells by the level of expression of CD45RB. Although the CD45RBhigh population mediated a protective response to L. major, C.B-17 scid mice restored with this population developed a severe inflammatory response in the colon that was independent of L. major infection, and was prevented by cotransfer of the CD45RBlow population. The colitis appeared to be due to a dysregulated Th1 response as anti-IFN-gamma, but not anti-IL-4, prevented it. Taken together, the data show that the CD4+ T cell population identified by high level expression of the CD45RB antigen contains cells that mediate both protective and pathogenic Th1 responses and that the reciprocal CD45RBlow population can suppress both of these responses. Whether suppression of cell-mediated immunity is beneficial or not depends on the nature of the stimulus, being deleterious during L. major infection but crucial for control of potentially pathogenic inflammatory responses developing in the gut.
Enhancement of Pulmonary Metastases Induced by Decreased Lung Natural Killer Cell Activity
Authors: D Nolibé, M F Poupon
Journal: JNCI Journal of the National Cancer Institute (1986)

Administration of repeated high doses of 7.5 mg chlorozotocin [(CZT) CAS: 54749-90-5]/kg to syngeneic WAG rats bearing the rhabdomyosarcoma 9-4/0 enhanced the incidence of spontaneous metastasis compared to its incidence in untreated rats. This enhancement was observed concomitantly with an increase in the survival of 9-4/0 rhabdomyosarcoma and P 77 fibrohistiocytoma tumor cells, labeled with [125I]5-iodo-2'-deoxyuridine or 51Cr and injected iv. Within the first 24 hours after P 77 cell injection, the lungs retained 10% of the cells while the lungs of controls or of rats given one CZT injection only retained 0.06%. The natural killer (NK) cell cytotoxicity of cells flushed out from lung capillaries [lung intracapillary cells (LIC)] was studied concomitantly in a 4-hour 51Cr release assa against YAC-1 and P 77 target cells. A large reduction was again observed in NK cytotoxicity but only after repeated injections of 7.5 mg CZT/kg. Lung defenses were gradually restored after treatment stopped. Administration of polyinosinic-polycytidylic acid with CZT restored the NK cell cytotoxicity of LIC and inhibited lung metastases amplification. The close relationship between metastasis and NK activity indicates the need for caution as regards the effects of chemotherapy on NK activity.
A Dap12-Mediated Pathway Regulates Expression of Cc Chemokine Receptor 7 and Maturation of Human Dendritic Cells
Authors: Axel Bouchon, Cristina Hernández-Munain, Marina Cella, Marco Colonna
Journal: The Journal of Experimental Medicine (2001)

Gene targeting of the adaptor molecule DAP12 in mice caused abnormal distribution and impaired antigen presentation capacity of dendritic cells (DCs). However, the DAP12-associated receptors expressed on DCs and their functions have not been identified yet. Here we show that the triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12. TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal–regulated kinase. In contrast to Toll-like receptor-mediated signaling, TREM2/DAP12 stimulation is independent of nuclear factor-κB and p38 stress-activated protein kinase. This novel DC activation pathway may regulate DC homeostasis and amplify DC responses to pathogens, explaining the phenotype observed in DAP12-deficient mice.
Use of Beta Adrenoceptor Blockade During and After Acute Myocardial Infarction
Authors: P Sleight
Journal: Annual Review of Medicine (1986)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Binet’s Staging System and VH Genes Are Independent but Complementary Prognostic Indicators in Chronic Lymphocytic Leukemia
Authors: Yuri Vasconcelos, Frédéric Davi, Vincent Levy, Pablo Oppezzo, Christian Magnac, Ariane Michel, Mihoko Yamamoto, Otto Pritsch, Hélène Merle-Béral, Karim Maloum, Florence Ajchenbaum-Cymbalista, Guillaume Dighiero
Journal: Journal of Clinical Oncology (2003)

Rai's and Binet's staging systems have contributed significantly to the identification of major prognostic groups in chronic lymphocytic leukemia (CLL), though they fail to accurately predict disease progression at the individual level. Biologic factors, such as the mutational status of the immunoglobulin heavy-chain variable genes (VH, cytogenetics, CD38 expression, and some serum markers, have recently improved prognostic assessment in CLL. In this study, we analyzed the prognostic value of VH mutational status within the different stages of Binet's classification in 145 patients.Our series consisted of 83 VH mutated (MT) and 62 VH unmutated (UM) patients. MT cases predominated within Binet's stage A (70%), whereas UM cases predominated among stages B and C (62%).Median overall survival (OS) was 84 months for UM patients and was not achieved for the MT group (70% 12-year survival, P <.0001). Concerning Binet's stage A, both median OS and progression-free survival were significantly shorter for UM patients when compared with those of MT patients (97 months v not achieved, P =.0017; and 42 v 156 months, P <.0001), which compared favorably with the classical A' and A" substaging. The VH mutational profile could also segregate stage B and C patients into two groups with different survival patterns (median OS, 78 v 120 months for UM and MT patients, respectively; P =.002).The significant survival differences observed between the VH mutational groups, among stage A and stage B and C patients, indicate that Binet's classification and VH genes are independent prognostic variables and are most likely complementary.
Not sleeping well? “Sleep Better”
Authors: Steffan Griffin
Journal: British Journal of Sports Medicine (2015)

<h3>ABSTRACT</h3> RT-LAMP (reverse transcription - Loop-mediated isothermal amplification) has gained popularity for the detection of SARS-CoV-2. The high specificity, sensitivity, simple protocols and potential to deliver results without the use of expensive equipment has made it an attractive alternative to RT-PCR. However, the high cost per reaction, the centralized manufacturing of required reagents and their distribution under cold chain shipping limits RT-LAMP's applicability in low-income settings. The preparation of assays using homebrew enzymes and buffers has emerged worldwide as a response to these limitations and potential shortages. Here, we describe the production of Moloney murine leukemia virus (M-MLV) Reverse Transcriptase and BstLF DNA polymerase for the local implementation of RT-LAMP reactions at low cost. These reagents compared favorably to commercial kits and optimum concentrations were defined in order to reduce time to threshold, increase ON/OFF range and minimize enzyme quantities per reaction. As a validation, we tested the performance of these reagents in the detection of SARS-CoV-2 from RNA extracted from clinical nasopharyngeal samples, obtaining high agreement between RT-LAMP and RT-PCR clinical results. The in-house preparation of these reactions results in an order of magnitude reduction in costs, and thus we provide protocols and DNA to enable the replication of these tests at other locations. These results contribute to the global effort of developing open and low cost diagnostics that enable technological autonomy and distributed capacities in viral surveillance.
Class III antiarrhythmic drug action in experimental atrial fibrillation. Differences in reverse use dependence and effectiveness between d-sotalol and the new antiarrhythmic drug ambasilide.
Authors: J Wang, J Feng, S Nattel
Journal: Circulation (1994)

BACKGROUND Drug therapy to maintain sinus rhythm in patients with atrial fibrillation (AF) is limited by adverse effects and inadequate efficacy. There has been an increased interest in the use of class III drugs to treat AF, and several new agents have been developed, but there is little information available about mechanisms of class III drug action in AF. The present study was designed to compare the effects of two class III agents, d-sotalol and ambasilide, in dog models of experimental AF. METHODS AND RESULTS A previously developed dog model of sustained vagotonic AF was used to assess the ability of equal loading doses of d-sotalol and ambasilide (2 mg/kg, followed by maintenance infusions), to terminate AF and prevent its induction. At this dose, ambasilide terminated AF in 12 of 12 dogs and prevented AF induction in 10 of 12 dogs; d-sotalol terminated AF in 1 of 8 dogs (P = .001 versus ambasilide) and prevented AF induction in none of 8 dogs (P = .002). An additional dose of d-sotalol (cumulative load, 8 mg/kg) terminated AF in 7 of 8 dogs and prevented induction in 5 of 8 dogs. In an additional 6 dogs with sterile pericarditis and inducible AF, ambasilide prevented AF induction in all 6. An equal dose of d-sotalol (2 mg/kg) failed to suppress AF induction in any dog, but 8 mg/kg of d-sotalol suppressed AF induction in all. Atrial effective refractory period (AERP) was increased by both drugs. However, the effects of d-sotalol on AERP showed strong reverse use dependence, whereas those of ambasilide did not. Neither ambasilide nor d-sotalol significantly altered conduction velocity, and both increased ventricular refractoriness, with d-sotalol once again showing more reverse use dependence. Effective doses of both agents increased AERP and the wavelength for atrial reentry at rapid rates, slowing atrial activation and terminating the arrhythmia. CONCLUSIONS The class III drugs d-sotalol and ambasilide terminate AF by increasing AERP and the wavelength for reentry. Ambasilide, which has been reported to block both the rapid and slow components of the delayed rectifier (IKr and IKs), shows less reverse use dependence of effects on refractoriness than the pure IKr blocker d-sotalol, possibly explaining the greater effectiveness of ambasilide at an equal dose level. These results indicate that class III drugs can exhibit different profiles of rate-dependent action on AERP and suggest that it may be possible to develop agents that have more desirable rate-dependent profiles than pure blockers of Ikr.
Prevalence and Correlates of Latent Autoimmune Diabetes in Adults in Tianjin, China
Authors: Xiuying Qi, Jing Sun, Jing Wang, Peizhong Peter Wang, Zhongliang Xu, Madonna Murphy, Junting Jia, Jianhua Wang, Yun Xie, Weili Xu
Journal: Diabetes Care (2010)

OBJECTIVE Data on latent autoimmune diabetes in adults (LADA) from population-based studies are sparse. We sought to investigate the prevalence and correlates of LADA. RESEARCH DESIGN AND METHODS A total of 8,109 participants, who were aged ≥15 years and living in Tianjin, China, were assessed to identify individuals with type 2 diabetes (American Diabetes Association Criteria, 1997) and further to detect patients with LADA. LADA was ascertained by 1) the presence of type 2 diabetes and age ≥35 years, 2) the lack of a requirement for insulin at least 6 months after the diagnosis of type 2 diabetes, and 3) serum GAD antibody positivity. Data were analyzed using multinomial logistic regression with adjustment for potential confounders. RESULTS Of all participants, 498 (6.1%) were patients with type 2 diabetes. Of them, 46 (9.2%) were found to have LADA. The prevalence of LADA was 0.6% (46 of 8,109), and tended to increase with age up to 50–59 years in all participants. The odds ratios (95% CI) of LADA related to hypertension, family history of diabetes, waist-to-hip ratio ≥0.85, and major stressful events were 1.93 (1.02–3.65), 17.59 (9.08–34.06), 5.37 (2.31–12.49), and 4.09 (1.75–9.52), respectively. CONCLUSIONS The prevalence of LADA is ∼9% in patients with type 2 diabetes. Hypertension, family history of diabetes, central obesity, and major stressful events may be associated with the occurrence of LADA.
Patient-Oncologist Alliance, Psychosocial Well-Being, and Treatment Adherence Among Young Adults With Advanced Cancer
Authors: Kelly M. Trevino, Karen Fasciano, Holly G. Prigerson
Journal: Journal of Clinical Oncology (2013)

Patients who develop a strong alliance with their health care providers have been shown to have higher levels of psychosocial well-being and rates of treatment adherence. Young adults with cancer have lower levels of psychosocial well-being and treatment adherence relative to patients with cancer in other age groups. This study sought to evaluate the relationships between the patient-oncologist alliance, psychosocial well-being, and treatment adherence in young adults with advanced cancer.
Adenovirus IgG avidity - A marker of outcome in COPD-exacerbations
Authors: Lucas Boeck, Mesut Gencay, Michael Tamm, Mirjam Christ-Crain, Beat Mueller, Michael Roth, Daiana Stolz
Journal: European Respiratory Journal (2012)

BACKGROUND:   Adenovirus causes respiratory infections in healthy and chronically ill adult individuals. Virus replication, cell lysis and inflammation provoke pulmonary damage. Little is known about adenovirus infection, reinfection and reactivation in acute exacerbations of COPD (AECOPD).   OBJECTIVES:   To evaluate effects of adenovirus infection during and after AECOPD.   METHODS:   208 patients with severe AECOPD were tested for anti-adenovirus antibodies at exacerbation and after two weeks. Outcome parameters were measured for two years.   RESULTS:   Studied patients were predominantly male (54.8%), had an age of 70.3 ±9.8 years, a FEV1 of 41.2 ±17.2 % predicted and smoked 45.2 ±27.9 pack years. At the time of exacerbation 39 patients (18.6 %) had anti-adenovirus IgM and low-avidity IgG, indicating a present adenovirus infection. At exacerbation, patients with acute adenovirus infection were younger (p=0.031) and presented a lower hospitalization rate in the previous year (p=0.037). In contrast, they reported a poorer health-related quality of life at admission (p=0.003) and persistendly impaired functional status 14 days after exacerbation (p=0.044). Patients with initial low-avidity adenovirus IgG who failed to convert into high-avidity adenovirus IgG within two weeks (n=13, 7%) had more recurrent AECOPDs within six months (1.23 vs. 0.63; p=0.032) and a shorter time to re-hospitalisation for AECOPD or death within two years (p=0.018).   CONCLUSION:   Adenovirus related severe AECOPDs potentially have a more severe clinical course. In addition, patients who remain at low-avidity adenovirus IgG are at higher risk for subsequent AECOPDs and hospitalisation or death.
Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer
Authors: Neil E. Martin, Laura Massey, Caleb Stowell, Chris Bangma, Alberto Briganti, Anna Bill-Axelson, Michael Blute, James Catto, Ronald C. Chen, Anthony V. D’Amico, Günter Feick, John M. Fitzpatrick, Steven J. Frank, Michael Froehner, Mark Frydenberg, Adam Glaser, Markus Graefen, Daniel Hamstra, Adam Kibel, Nancy Mendenhall, Kim Moretti, Jacob Ramon, Ian Roos, Howard Sandler, Francis J. Sullivan, David Swanson, Ashutosh Tewari, Andrew Vickers, Thomas Wiegel, Hartwig Huland
Journal: European Urology (2014)

Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment.To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value.We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices.The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set.We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons.We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care.Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.
SEX-LINKED INHERITANCE IN MENTAL DEFICIENCY
Authors: Aaron J. Rosanoff
Journal: American Journal of Psychiatry (1931)

1. Mental deficiency seems to be consistently more common in the male than in the female sex. 2. This is most strikingly shown in opposite-sex twins. Among 27 pairs of opposite-sex twins, both had mental deficiency in 11 instances, the male alone in 11 instances, and the female alone in 5 instances. 3. It appears in a similarly consistent way that girls make a slightly better showing than boys in intelligence tests and in scholastic record. 4. These facts suggest that gene factors of intelligence may in some cases be carried in the X-chromosomes and not only in the autosomes; or, in other words, that there may be a sex-linked factor in some cases in the genetic history of mental deficiency and of general intelligence. 5. In order to make the simplest provision in biological symbols and formulas for a sex-linked factor, it is necessary to assume the existence of six possible types of males, nine types of females, and 54 types of mating. 6. Theoretically, from 38 of these types of mating only normal offspring can result. 7. The mentally deficient offspring that may result from eight other types of mating may be expected to be eqaully distributed in the two sexes, as far as the possible influence of any sex-linked factor is concerned. 8. Only male mentally deficient offspring can result from the remaining eight types of mating. 9. Among phenotypes it is, of course, impossible to distinguish the various genotypes represented in the symbols and formulas listed in this paper. However, it may be readily deduced from the formulas that when both parents are mentally deficient or when the father alone is mentally deficient, an equal distribution of mental deficiency in the two sexes of offspring may be expected. When both parents are normal or when the mother alone is mentally deficient, then, too, mentally deficient offspring of both sexes may result; but their distribution will not be equal in the two sexes, for the cases in which a sex-linked factor may be operative will be included in this part of the material. Here, according to theory, any relative excess of mental deficiency in the male sex must be, at least in part, attributed to a sex-linked factor. 10. A re-investigation of a part of Goddard's published material, selected by reason of relevancy to the questions raised in this contribution, bears out the assumption of a sex-linked factor in the genetic history of mental deficiency. The general relative excess of mental deficiency in the male sex is, however, greater than can be accounted for by this factor; to some extent it must be attributed to some other factor or factors.