tbuckley/cabot-search huggingface dataset:
The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene.
Authors: S Vidal, M L Tremblay, G Govoni, S Gauthier, G Sebastiani, D Malo, E Skamene, M Olivier, S Jothy, P Gros
Journal: The Journal of Experimental Medicine (1995)

In mice, natural resistance or susceptibility to infection with intracellular parasites is determined by a locus or group of loci on chromosome 1, designated Bcg, Lsh, and Ity, which controls early microbial replication in reticuloendothelial organs. We have identified by positional cloning a candidate gene for Bcg, Nramp1, which codes for a novel macrophage-specific membrane transport protein. We have created a mouse mutant bearing a null allele at Nramp1, and we have analyzed the effect of such a mutation on natural resistance to infection. Targeted disruption of Nramp1 has pleiotropic effects on natural resistance to infection with intracellular parasites, as it eliminated resistance to Mycobacterium bovis, Leishmania donovani, and lethal Salmonella typhimurium infection, establishing that Nramp1, Bcg, Lsh, and Ity are the same locus. Comparing the profiles of parasite replication in control and Nramp1-/- mice indicated that the Nramp1Asp169 allele of BcgS inbred strains is a null allele, pointing to a critical role of this residue in the mechanism of action of the protein. Despite their inability to control parasite growth in the early nonimmune phase of the infection, Nramp1-/- mutants can overcome the infection in the late immune phase, suggesting that Nramp1 plays a key role only in the early part of the macrophage-parasite interaction and may function by a cytocidal or cytostatic mechanism distinct from those expressed by activated macrophages.
Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome
Authors: Kamal Rahmouni, Melissa A. Fath, Seongjin Seo, Daniel R. Thedens, Christopher J. Berry, Robert Weiss, Darryl Y. Nishimura, Val C. Sheffield
Journal: Journal of Clinical Investigation (2008)

Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder characterized by many features, including obesity and cardiovascular disease. We previously developed knockout mouse models of 3 BBS genes: BBS2, BBS4, and BBS6. To dissect the mechanisms involved in the metabolic disorders associated with BBS, we assessed the development of obesity in these mouse models and found that BBS-null mice were hyperphagic, had low locomotor activity, and had elevated circulating levels of the hormone leptin. The effect of exogenous leptin on body weight and food intake was attenuated in BBS mice, which suggests that leptin resistance may contribute to hyperleptinemia. In other mouse models of obesity, leptin resistance may be selective rather than systemic; although mice became resistant to leptin's anorectic effects, the ability to increase renal sympathetic nerve activity (SNA) was preserved. Although all 3 of the BBS mouse models were similarly resistant to leptin, the sensitivity of renal SNA to leptin was maintained in Bbs4 -/- and Bbs6 -/- mice, but not in Bbs2 -/- mice. Consequently, Bbs4 -/- and Bbs6 -/- mice had higher baseline renal SNA and arterial pressure and a greater reduction in arterial pressure in response to ganglionic blockade. Furthermore, we found that BBS mice had a decreased hypothalamic expression of proopiomelanocortin, which suggests that BBS genes play an important role in maintaining leptin sensitivity in proopiomelanocortin neurons.
A NEW PROGRAM IN THE TRAINING AND EMPLOYMENT OF WARD PERSONNEL
Authors: D. G. MCKERRACHER
Journal: American Journal of Psychiatry (1949)

We feel that the project, started over 2 years ago, has already certain accomplishments to its credit. It has been proved that it is possible to recruit intelligent, well-educated men and women who are motivated to devote themselves to psychiatric nursing as a career. It has been shown that it is possible to make function an intensive, 500-hour training program to prepare the members of this ward staff for future responsibilities. It is still too early to judge how effectively this staff can carry out the therapeutic responsibilies assigned to them, or to determine whether the task is sufficienty challenging to hold their interest and keep them as members of a professional group. Even though the ultimate therapeutic limit of this ward staff has not been ascertained, our experience has convinced us that the success of any mental hospital program is dependent upon highly qualified and well-trained nursing personnel.
Immunotherapy with Dendritic Cells Directed against Tumor Antigens Shared with Normal Host Cells Results in Severe Autoimmune Disease
Authors: Burkhard Ludewig, Adrian F. Ochsenbein, Bernhard Odermatt, Denise Paulin, Hans Hengartner, Rolf M. Zinkernagel
Journal: The Journal of Experimental Medicine (2000)

Vaccination with dendritic cells (DCs) presenting tumor antigens induces primary immune response or amplifies existing cytotoxic antitumor T cell responses. This study documents that antitumor treatment with DCs may cause severe autoimmune disease when the tumor antigens are not tumor-specific but are also expressed in peripheral nonlymphoid organs. Growing tumors with such shared tumor antigens that were, at least initially, strictly located outside of secondary lymphoid organs were successfully controlled by specific DC vaccination. However, antitumor treatment was accompanied by fatal autoimmune disease, i.e., autoimmune diabetes in transgenic mice expressing the tumor antigen also in pancreatic β islet cells or by severe arteritis, myocarditis, and eventually dilated cardiomyopathy when arterial smooth muscle cells and cardiomyocytes expressed the transgenic tumor antigen. These results reveal the delicate balance between tumor immunity and autoimmunity and therefore point out important limitations for the use of not strictly tumor-specific antigens in antitumor vaccination with DCs.
The effect of two golimumab doses on radiographic progression in ankylosing spondylitis: results through 4 years of the GO-RAISE trial
Authors: Jürgen Braun, Xenofon Baraliakos, Kay-Geert A Hermann, Atul Deodhar, Désirée van der Heijde, Robert Inman, Anna Beutler, Yiying Zhou, Stephen Xu, Benjamin Hsu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To evaluate radiographic progression in patients with ankylosing spondylitis (AS) receiving two different doses of the tumour necrosis factor antagonist golimumab. <h3>Methods</h3> 356 patients with AS were randomly assigned to placebo, or golimumab 50 mg or 100 mg every 4 weeks (wks). At wk16, patients with inadequate response early escaped with blinded dose adjustments (placebo→golimumab 50 mg, 50 mg→100 mg). At wk24, patients still receiving placebo crossed over to golimumab 50 mg. Lateral view radiographs of the cervical/lumbar spine were obtained at wk0, wk104 and wk208, and scored (two blinded readers, modified Stoke AS Spine Score (mSASSS)). Observed data were used for wk104 analyses; missing wk208 scores were linearly extrapolated. <h3>Results</h3> Wk104 changes from baseline in mSASSS averaged 1.6±4.6 for placebo crossover, 0.9±2.7 for 50 mg and 0.9±3.9 for 100 mg. By wk208, following golimumab therapy for 3.5–4 years, mean changes in mSASSS were 2.1±5.2 for placebo crossover, 1.3±4.1 for 50 mg and 2.0±5.6 for 100 mg. Less than a third of patients (placebo crossover, 19/66 (28.8%); 50 mg, 29/111 (26.1%); 100 mg, 35/122 (28.7%)) had a definitive change from baseline mSASSS (&gt;2). Less radiographic progression was observed through wk208 in patients without baseline syndesmophytes (0.2 vs 2.8 in patients with ≥1 syndesmophyte; p&lt;0.0001) and with baseline C-reactive protein (CRP) levels ≤1.5 mg/dl (0.9 vs 2.9 with CRP &gt;1.5 mg/dl; p=0.0004). <h3>Conclusions</h3> No difference in mSASSS change was observed between golimumab 50 mg and 100 mg. The radiographic progression rate remained stable at years 2 and 4, suggesting no acceleration of new bone formation over time. Golimumab-treated AS patients with no syndesmophytes and less systemic inflammation at baseline had considerably less radiographic progression.
Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus
Authors: J B M van Woensel
Journal: Thorax (2003)

<b>Background:</b> A study was undertaken to evaluate the efficacy of dexamethasone in patients mechanically ventilated for lower respiratory infection caused by respiratory syncytial virus (RSV-LRTI). <b>Methods:</b> In a multicentre randomised controlled trial patients were randomised to receive either intravenous dexamethasone (0.15 mg/kg 6 hourly for 48 hours) or placebo. End points were the duration of mechanical ventilation, length of stay (LOS) in the pediatric intensive care unit (PICU) and in hospital, and the duration of supplemental oxygen administration. <b>Results:</b> Thirty seven patients received dexamethasone and 45 received placebo. There was no significant difference in any of the end points between the two groups. In a post hoc analysis patients were stratified into those with mild gas exchange anomalies (Pao<sub>2</sub>/Fio<sub>2</sub> &gt;200 mm Hg and/or mean airway pressure ⩽ 10 cm H<sub>2</sub>O, bronchiolitis group) and those with severe gas exchange anomalies (Pao<sub>2</sub>/Fio<sub>2</sub> ⩽200 mm Hg and mean airway pressure &gt;10 cm H<sub>2</sub>O, pneumonia group). In the 39 patients with bronchiolitis the duration of mechanical ventilation was 4.3 days shorter in the dexamethasone group than in the placebo group (4.9 <i>v</i> 9.2 days, 95% CI −7.8 to −0.8, p=0.02) and the duration of supplemental oxygen was 3.6 days shorter (7.7 <i>v</i> 11.3 days, 95% CI −8.0 to −0.1, p=0.048). No differences in end points were found in the pneumonia group. <b>Conclusions:</b> Dexamethasone had no beneficial effect in patients mechanically ventilated for RSV-LRTI but was found to have a beneficial effect in patients with bronchiolitis.
Fluid-containing emphysematous bullae: a spectrum of illness
Authors: D. Chandra, S. R. Rose, R. B. Carter, D. M. Musher, R. J. Hamill
Journal: European Respiratory Journal (2008)

Fluid-containing emphysematous bullae are an under-reported complication of chronic obstructive pulmonary disease. The roles of bronchoscopy in the work-up and of antibiotics in the treatment are undefined. This study reports the combined results from the analysis of 16 cases treated at the present authors’ institution and 36 previously reported cases. The median age at presentation was 58 yrs and the median duration of follow-up was 60 weeks. A third of the patients were asymptomatic, while two-thirds presented with symptoms, including 10% who had evidence of a severe lung infection. Methicillin-resistant Staphylococcus aureus , Pseudomonas aeruginosa and Bacteroides melaninogenicus were cultured from the bullae fluid in three symptomatic patients. Sputum and blood cultures were uninformative. Bronchoscopy, performed in two-thirds of the cases, added no diagnostic information. Antibiotic treatment did not result in a more rapid resolution of the air fluid level. Percutaneous drainage was safe and effective in four patients. In conclusion, patients with fluid-containing bullae present with a spectrum of illness. Antibiotic treatment does not hasten radiographic resolution and bronchoscopy has no diagnostic or therapeutic role.
Incremental Costs of Enrolling Cancer Patients in Clinical Trials: a Population-Based Study
Authors: J. L. Wagner
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Payment for care provided as part of clinical research has become less predictable as a result of managed care. Because little is known at present about how entry into cancer trials affects the cost of care for cancer patients, we conducted a matched case-control comparison of the incremental medical costs attributable to participation in cancer treatment trials. METHODS: Case patients were residents of Olmsted County, MN, who entered phase II or phase III cancer treatment trials at the Mayo Clinic from 1988 through 1994. Control patients were patients who did not enter trials but who were eligible on the basis of tumor registry matching and medical record review. Sixty-one matched pairs were followed for up to 5 years after the date of trial entry for case patients or from an equivalent date for control patients. Hospital, physician, and ancillary service costs were estimated from a population-based cost database developed at the Mayo Clinic. RESULTS: Trial enrollees incurred modestly (no more than 10%) higher costs over various follow-up periods. The mean cumulative 5-year cost in 1995 inflation-adjusted U.S. dollars among trial enrollees after adjustment for censoring was $46 424 compared with $44 133 for control patients. After 1 year, trial enrollee costs were $24 645 compared with $23 964 for control patients. CONCLUSIONS: This study suggests that cancer chemotherapy trials may not imply budget-breaking costs. Cancer itself is a high-cost illness. Clinical protocols may add relatively little to that cost.
Salmonella: A Model for Bacterial Pathogenesis
Authors: Michael E. Ohl, Samuel I. Miller
Journal: Annual Review of Medicine (2001)

▪ Abstract Salmonellae are gram-negative bacteria that cause gastroenteritis and enteric fever. Salmonella virulence requires the coordinated expression of complex arrays of virulence factors that allow the bacterium to evade the host's immune system. All Salmonella serotypes share the ability to invade the host by inducing their own uptake into cells of the intestinal epithelium. In addition, Salmonella serotypes associated with gastroenteritis orchestrate an intestinal inflammatory and secretory response, whereas serotypes that cause enteric fever establish systemic infection through their ability to survive and replicate in mononuclear phagocytes. This review explores the molecular basis of selected Salmonella virulence strategies, with an emphasis on general themes of bacterial pathogenesis as exemplified by Salmonella.
Systemic Fibrinolysis Caused by Tissue Plasminogen Activator–Producing Metastatic Breast Cancer
Authors: Harris V.K. Naina, Mrinal M. Patnaik, Uzma A. Ali, Dong Chen, Aneel A. Ashrani
Journal: Journal of Clinical Oncology (2010)

A 63-year-old woman with treated stage I (T1cN0M0), estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, human epidermal growth factor receptor 2-negative, infiltrating ductal breast cancer presented with extensive spontaneous ecchymoses.She had undergone a right modified radical mastectomy, followed by six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) and adjuvant hormonal therapy with letrozole for 3 years before presentation.The ecchymoses were first noted on the left hand, and they progressed over the next few days to involve the entire left upper limb.Subsequently, she developed soft tissue bleeding and hematuria.A computed tomography scan of the abdomen revealed nonobstructing renal calculi.Incidentally, multiple lytic and sclerotic lesions were noted in the thoracic and lumbar spine and both hips.She did not have a past history suggestive of a bleeding disorder and had successfully undergone invasive procedures such as mastectomy and breast reconstruction uneventfully.The patient was found to be anemic (hemoglobin, 9.4 g/dL), with a normal platelet count.Her prothrombin time, activated partial thromboplastic time, and thrombin DAPI PR TPA 30 μm 30 μm 20 μm DAPI PR TPA Fig 1.
31 SAFETY AND ANTIVIRAL ACTIVITY OF THE HCV NON-NUCLEOSIDE POLYMERASE INHIBITOR VX-222 IN TREATMENT-NAIVE GENOTYPE 1 HCV-INFECTED PATIENTS
Authors: M. Rodriguez-Torres, E. Lawitz, B. Conway, K. Kaita, A.M. Sheikh, R. Ghalib, R. Adrover, C. Cooper, M. Silva, M. Rosario, B. Bourgault, L. Proulx, J.G. McHutchison
Journal: Journal of Hepatology (2010)
Outcomes and Prognostic Factors in 267 Patients with Severe Acute Respiratory Syndrome in Hong Kong
Authors: Kin Wing Choi, Tai Nin Chau, Owen Tsang, Eugene Tso, Ming Chee Chiu, Wing Lok Tong, Po Oi Lee, Tak Keung Ng, Wai Fu Ng, Kam Cheong Lee, William Lam, Wai Cho Yu, Jak Yiu Lai, Sik To Lai
Journal: Annals of Internal Medicine (2003)

Background: Severe acute respiratory syndrome (SARS) has become a global public health emergency. Objective: To evaluate the characteristics and outcomes of patients with SARS in Hong Kong and to identify predictors of mortality. Design: Retrospective cohort study. Setting: Quarantine hospital for patients with SARS in Hong Kong. Patients: 267 consecutive patients hospitalized from 26 February to 31 March 2003 for probable or confirmed SARS. Measurements: Clinical, laboratory, and radiographic measures; 3-month mortality rate. Results: According to our case definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS. Common presenting symptoms were fever (99% of patients), chills (74%), malaise (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%), thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate dehydrogenase (47%) and C-reactive protein (75%). During hospitalization, incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%) increased. Sixty-nine patients (26%) required intensive care because of respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%). Factors contributing to mortality were respiratory failure, acute renal failure, and nosocomial sepsis. On multivariate Cox regression, age older than 60 years (relative risk, 5.10 [CI, 2.30 to 11.31]; P<0.001) and lactate dehydrogenase level greater than 3.8 kat/L at presentation (relative risk, 2.20 [CI, 1.03 to 4.71]; P=0.04) were independent predictors of mortality. Conclusion: Because of the longer follow-up period in our cohort, the mortality rate in these patients is higher than rates reported in previous studies. Advanced age and high lactate dehydrogenase level at presentation predict mortality. *For members of the Princess Margaret Hospital SARS Study Group, see the Appendix.
Immunoglobulin light chain amyloidosis is diagnosed late in patients with preexisting plasma cell dyscrasias
Authors: Taxiarchis V. Kourelis, Shaji K. Kumar, Ronald S. Go, Prashant Kapoor, Robert A. Kyle, Francis K. Buadi, Morie A. Gertz, Martha Q. Lacy, Suzanne R. Hayman, Nelson Leung, David Dingli, John A. Lust, Yi Lin, Stephen R. Zeldenrust, S. Vincent Rajkumar, Angela Dispenzieri
Journal: American Journal of Hematology (2014)

AL amyloidosis (AL) is rare and frequently remains undiagnosed until organ function is compromised, even among patients with known pre-existing untreated plasma cell dyscrasias (PCD). We identified 168 patients with AL amyloidosis who had a prior untreated PCD. The earliest symptom or sign (s/s) was defined as the first symptom reported by the patient that could be attributed to organ dysfunction caused by AL. The interval from the time of development of s/s to the establishment of diagnosis of AL (Interval-SA) was calculated. PCD diagnosis preceded recorded onset of s/s in 75% (114/152) of patients, with a median interval-SA for this group of 10 months. PCD was diagnosed after s/s in 25% (38/152) of patients, with a median interval-SA of 20 months. Overall survival (OS) from diagnosis of AL was not different between the two groups. AL amyloidosis patients with an identified pre-existing PCD had less advanced cardiac disease at AL diagnosis when compared to a control group of AL patients without pre-identified PCD. Long-term OS was not significantly superior among patients with a pre-identified PCD. In patients with "asymptomatic" PCD, symptoms and signs of AL amyloidosis should be solicited, since timely diagnosis is important in AL amyloidosis.
Differences in Bet v 1 epitope specificies of individual patients' IgE revealed by analysis of cross-reactivity between group 1 major allergens from birch and apple
Authors: Jørgen N Larsen, Jeanette Haugel-Nielsen, JH Heinig, Jens Holm, Henrik Ipsen, Henrik H Jacobi, Peter Adler Würtzen, Michael D Spangfort
Journal: Journal of Allergy and Clinical Immunology (2002)
Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia
Authors: J. Rello, A. Rodriguez, A. Torres, J. Roig, J. Sole-Violan, J. Garnacho-Montero, M. V. de la Torre, J. M. Sirvent, M. Bodi
Journal: European Respiratory Journal (2006)

The mortality rate of chronic obstructive pulmonary disease (COPD) patients with community-acquired pneumonia (CAP) is reported to be low. However, studies carried out to date have included &lt;20% of critically ill patients. The current authors performed a secondary analysis of a prospective study evaluating 428 immunocompetent patients admitted to the intensive care unit (ICU) for severe CAP. In total, 176 COPD patients were compared with 252 non-COPD patients. In COPD patients, ICU mortality (odds ratio (OR) 1.58; 95% confidence interval (CI) 1.01–1.43) and mechanical ventilation (OR 2.78; 95% CI 1.63–4.74) rates were higher than in non-COPD patients. The ICU mortality was 39% for COPD patients initially intubated and 50% for those who failed noninvasive ventilation. The proportion of patients who were males, aged ≥70 yrs, smokers and who had chronic heart disease or Pseudomonas aeruginosa were higher in COPD patients. Inappropriate empirical antibiotic therapy was associated with higher mortality (OR 3.8; 95% CI 1.19–12.6). ICU mortality in COPD patients with adequate therapy was associated with bilateral pneumonia (OR 2.32; 95% CI 1.18–4.53) and shock (OR 3.53; 95% CI 1.31–9.71). In conclusion, chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia in the intensive care unit had higher mortality and need of mechanical ventilation when compared with patients without chronic obstructive pulmonary disease.
Different slopes for different folks: socioeconomic and racial/ethnic disparities in asthma and hay fever among 173,859 U.S. men and women.
Authors: Jarvis T Chen, Nancy Krieger, Stephen K Van Den Eeden, Charles P Quesenberry
Journal: Environmental Health Perspectives (2002)

Although allergic diseases such as asthma and hay fever are a major cause of morbidity in industrialized countries, most studies have focused on patterns of prevalence among children and adolescents, with relatively few studies on variations in prevalence by race/ethnicity and socioeconomic position among adults. Our study examined racial/ethnic and socioeconomic patterns in the prevalence of asthma overall, asthma with hay fever, asthma without hay fever, and hay fever overall, in a population of 173,859 women and men in a large prepaid health plan in northern California. Using education as a measure of socioeconomic position, we found evidence of a positive gradient for asthma with hay fever with increasing level of education but an inverse gradient for asthma without hay fever. Hay fever was also strongly associated with education. Compared with their White counterparts, Black women and men were more likely to report asthma without hay fever, and Black women were less likely to have asthma with hay fever. Asian men were also more likely to report asthma with hay fever, and Asian women and men were much more likely to have hay fever. Racial/ethnic disparities in prevalence of allergic diseases were largely independent of education. We discuss implications for understanding these social inequalities in allergic disease risk in relation to possible differences in exposure to allergens and determinants of immunologic susceptibility and suggest directions for future research.