tbuckley/cabot-search huggingface dataset:
Myelin/oligodendrocyte glycoprotein–deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice
Authors: Cécile Delarasse, Philippe Daubas, Lennart T. Mars, Csaba Vizler, Tobias Litzenburger, Antonio Iglesias, Jan Bauer, Bruno Della Gaspera, Anna Schubart, Laurence Decker, Dalia Dimitri, Guy Roussel, Andrée Dierich, Sandra Amor, André Dautigny, Roland Liblau, Danielle Pham-Dinh
Journal: Journal of Clinical Investigation (2003)

We studied the immunological basis for the very potent encephalitogenicity of myelin/oligodendrocyte glycoprotein (MOG), a minor component of myelin in the CNS that is widely used to induce experimental autoimmune encephalomyelitis (EAE). For this purpose, we generated a mutant mouse lacking a functional mog gene. This MOG-deficient mouse presents no clinical or histological abnormalities, permitting us to directly assess the role of MOG as a target autoantigen in EAE. In contrast to WT mice, which developed severe EAE following immunization with whole myelin, MOG-deficient mice had a mild phenotype, demonstrating that the anti-MOG response is a major pathogenic component of the autoimmune response directed against myelin. Moreover, while MOG transcripts are expressed in lymphoid organs in minute amounts, both MOG-deficient and WT mice show similar T and B cell responses against the extracellular domain of MOG, including the immunodominant MOG 35–55 T cell epitope. Furthermore, no differences in the fine specificity of the T cell responses to overlapping peptides covering the complete mouse MOG sequence were observed between MOG+/+ and MOG–/– mice. In addition, upon adoptive transfer, MOG-specific T cells from WT mice and those from MOG-deficient mice are equally pathogenic. This total lack of immune tolerance to MOG in WT C57BL/6 mice may be responsible for the high pathogenicity of the anti-MOG immune response as well as the high susceptibility of most animal strains to MOG-induced EAE.
Enhancement of Natural Killer Activity in Human Peripheral Blood by Flavone Acetic Acid
Authors: W. J. Urba, D. L Longo, F. A. Lombardo, R. B. Weiss
Journal: JNCI Journal of the National Cancer Institute (1988)

Natural killer cell activity and in-terferon (IFN) production were measured in 6 patients receiving flavone acetic acid for treatment of cancer. Natural killer cell activity was significantly increased in 3 of 6 patients receiving 6.4 g of flavone acetic acid/m2 by 3-hour iv infusion. Analysis of cell surface markers failed to reveal significant changes in any cell population. There was no evidence of induction of IFN-gamma, but 3 of 4 patients tested had evidence of induction of type I IFN, as measured in a virus neutralization assay.
When I use a word . . .: Addressing the issue
Authors: Neville W Goodman
Journal: BMJ (2001)

“address (v) 1 write someone's name on (envelope or parcel). 2 speak formally to, direct one's remarks to. 3 think about and begin to deal with. 4 (golf) prepare to hit (the ball).”1

Address in its third sense has joined “involve” as a “lazily overused”2 verb that “makes it the delight of those who dislike the effort of searching for the right word”3 or “the trouble of precise thought.”4 Searching bmj.com for “addresses” or “addressing” mines a rich seam. There is almost nothing that cannot be addressed: arguments, definitions, expectations, gaps, inequalities, representativeness, risks, shortages, threats, variations, and even what is right and what is wrong.

What is wrong with all these uses of address is that we do not know what the writers intend. When arguments are addressed, are they defined, considered, accepted, or countered? Are expectations being described, denied, or realised? Are variations being analysed, categorised, or reduced? Most popular for addressing are issues and questions, which is an even higher level of vagueness because the issue or question will be one of definitions, expectations, gaps, inequalities, and so on. If a question is addressed, is it framed, asked, or answered? Any word has to be treated with suspicion if context or motive can switch its meaning between “ask” and “answer”.

Sometimes, address is not needed at all: “only the t test . . . addresses a comparison of arithmetic means” means simply “the t test compares arithmetic means.”

In the retrieved issues of bmj.com, the verb address was used for its precise meanings just twice in 92 uses: once for addressing a conference and once for a consideration of Mr or Dr being the correct way to address a surgeon. Given the popularity of the golf course as a place of recreation for doctors, perhaps it is surprising it was never used for its other precise meaning.
Increasing Dialysate Flow and Dialyzer Mass Transfer Area Coefficient to Increase the Clearance of Protein-bound Solutes
Authors: Timothy W. Meyer, Evonne C. Leeper, Derek W. Bartlett, Thomas A. Depner, Yiming Zhao Lit, Channing R. Robertson, Thomas H. Hostetter
Journal: Journal of the American Society of Nephrology (2004)

Clinical hemodialysis systems achieve high single pass extraction of small solutes that are not bound to plasma proteins. But they clear protein-bound solutes much less effectively. This study examines the extent to which clearance of a protein-bound test solute is improved by increasing the dialyzer mass transfer area coefficient (KoA) and the dialysate flow rate (Qd). A reservoir containing test solutes and artificial plasma with albumin concentration approximately 4 g/dl was dialyzed with a standard clinical dialysate delivery system. The clearance of phenol red (ClPR) was compared with the clearances of urea and creatinine at a plasma flow rate (Qp) of 200 ml/min with varying values of KoA and Qd. ClPR increased from 11 +/- 2 ml/min to 23 +/- 2 ml/min when KoA for phenol red, KoAPR, was increased from 238 to 640 ml/min and Qd was increased from 286 +/- 6 ml/min to 734 +/- 9 ml/min. Increasing either KoAPR or Qd alone had lesser effects. Clearance values for phenol red were much lower than clearance values for the unbound solutes urea and creatinine, which ranged from 150 to 200 ml/min and were less affected by varying KoA and Qd. A mathematical model was developed to predict ClPR from values of Qp, Qd, the fraction of phenol red bound to albumin (94% +/- 1%) and KoAPR. The model accurately predicts the pattern of measured results and shows further that ClPR can be made to approach Qp only by very large increases in both KoAPR and Qd.
Panic, Paranoia, and Public Health — The AIDS Epidemic's Lessons for Ebola
Authors: Gregg Gonsalves, Peter Staley
Journal: New England Journal of Medicine (2014)

The scientific ignorance and paranoia on display in the reaction to the return of health care workers from the front lines of the Ebola fight and the fear-driven suspicion and shunning of whole classes of people echo the response to the emergence of AIDS in the 1980s.
The resistive and elastic work of breathing during exercise in patients with chronic heart failure
Authors: Troy J. Cross, Surendan Sabapathy, Kenneth C. Beck, Norman R. Morris, Bruce D. Johnson
Journal: European Respiratory Journal (2011)

Patients with heart failure (HF) display numerous derangements in ventilatory function, which together serve to increase the work of breathing ( W b ) during exercise. However, the extent to which the resistive and elastic properties of the respiratory system contribute to the higher W b in these patients is unknown. We quantified the resistive and elastic W b in patients with stable HF (n=9; New York Heart Association functional class I–II) and healthy control subjects (n=9) at standardised levels of minute ventilation ( V ′ E ) during graded exercise. Dynamic lung compliance was systematically lower for a given level of V ′ E in HF patients than controls (p&lt;0.05). HF patients displayed slightly higher levels of inspiratory elastic W b with greater amounts of ventilatory constraint and resistive W b than control subjects during exercise (p&lt;0.05). Our data indicates that the higher W b in HF patients is primarily due to a greater resistive, rather than elastic, load to breathing. The greater resistive W b in these patients probably reflects an increased hysteresivity of the airways and lung tissues. The marginally higher inspiratory elastic W b observed in HF patients appears related to a combined decrease in the compliances of the lungs and chest wall. The clinical and physiological implications of our findings are discussed.
Nodal Status and Clinical Outcomes in a Large Cohort of Patients With Triple-Negative Breast Cancer
Authors: Leonel F. Hernandez-Aya, Mariana Chavez-MacGregor, Xiudong Lei, Funda Meric-Bernstam, Thomas A. Buchholz, Limin Hsu, Aysegul A. Sahin, Kim-Anh Do, Vicente Valero, Gabriel N. Hortobagyi, Ana Maria Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2011)

Purpose To evaluate the clinical outcomes and relationship between tumor size, lymph node status, and prognosis in a large cohort of patients with confirmed triple receptor–negative breast cancer (TNBC). Patients and Methods We reviewed 1,711 patients with TNBC diagnosed between 1980 and 2009. Patients were categorized by tumor size and nodal status. Kaplan-Meier product limit method was used to calculate overall survival (OS) and relapse-free survival (RFS). A Sidak adjustment was used for multiple group comparisons. Cox proportional hazards models were fit to determine the association of tumor size and nodal status with survival outcomes after adjustment for other patient and disease characteristics. Results Median age was 48 years (range, 21 to 87 years). At a median follow-up of 53 months (range, 0.7 to 317 months), there were 614 deaths and 747 recurrences. The 5-year OS was 80% for node-negative patients (N0), 65% for one to three positive lymph nodes (N1), 48% for four to nine positive lymph nodes (N2), and 44% for ≥ 10 positive lymph nodes (N3; P &lt; .0001). The 5-year RFS rates were 67% for N0, 52% for N1, 36% for N2, and 33% for N3 (P &lt; .0001). Pairwise comparison by nodal status showed that when comparing N0 with node-positive disease, there was a significant difference in OS and RFS (P &lt; .001 all comparisons). However, when comparing N1 with N2 and N3 disease regardless of tumor size, there were no significant differences in OS or RFS. Conclusion In patients with TNBC, once there is evidence of lymph node metastasis, the prognosis may not be affected by the number of positive lymph nodes.
Immediate Risk for Cardiovascular Events and Suicide Following a Prostate Cancer Diagnosis: Prospective Cohort Study
Authors: Katja Fall, Fang Fang, Lorelei A. Mucci, Weimin Ye, Ove Andrén, Jan-Erik Johansson, Swen-Olof Andersson, Pär Sparén, Georg Klein, Meir Stampfer, Hans-Olov Adami, Unnur Valdimarsdóttir
Journal: PLoS Medicine (2009)

Stressful life events have been shown to be associated with altered risk of various health consequences. The aim of the present study was to investigate whether the emotional stress evoked by a prostate cancer diagnosis increases the immediate risks of cardiovascular events and suicide.We conducted a prospective cohort study by following all men in Sweden who were 30 y or older (n = 4,305,358) for a diagnosis of prostate cancer (n = 168,584) and their subsequent occurrence of cardiovascular events and suicide between January 1, 1961 and December 31, 2004. We used Poisson regression models to calculate relative risks (RRs) and 95% confidence intervals (CIs) of cardiovascular events and suicide among men who had prostate cancer diagnosed within 1 y to men without any cancer diagnosis. The risks of cardiovascular events and suicide were elevated during the first year after prostate cancer diagnosis, particularly during the first week. Before 1987, the RR of fatal cardiovascular events was 11.2 (95% CI 10.4-12.1) during the first week and 1.9 (95% CI 1.9-2.0) during the first year after diagnosis. From 1987, the RR for cardiovascular events, nonfatal and fatal combined, was 2.8 (95% CI 2.5-3.2) during the first week and 1.3 (95% CI 1.3-1.3) during the first year after diagnosis. While the RR of cardiovascular events declined, the RR of suicide was stable over the entire study period: 8.4 (95% CI 1.9-22.7) during the first week and 2.6 (95% CI 2.1-3.0) during the first year after diagnosis. Men 54 y or younger at cancer diagnosis demonstrated the highest RRs of both cardiovascular events and suicide. A limitation of the present study is the lack of tumor stage data, which precluded possibilities of investigating the potential impact of the disease severity on the relationship between a recent diagnosis of prostate cancer and the risks of cardiovascular events and suicide. In addition, we cannot exclude residual confounding as a possible explanation.Men newly diagnosed with prostate cancer are at increased risks for cardiovascular events and suicide. Future studies with detailed disease characteristic data are warranted.
Muscle Mechanoreflex and Metaboreflex Responses After Myocardial Infarction in Rats
Authors: Jianhua Li, Adam N. Sinoway, Zhaohui Gao, Michael D. Maile, Min Pu, Lawrence I. Sinoway
Journal: Circulation (2004)

During exercise, the sympathetic nervous system is activated and blood pressure and heart rate increase. In heart failure (HF), the muscle metaboreceptor contribution to sympathetic outflow is attenuated and the mechanoreceptor contribution is accentuated. Previous studies suggest that (1) capsaicin stimulates muscle metabosensitive vanilloid receptor subtype 1 (VR1), inducing a neurally mediated pressor response, and (2) activation of ATP-sensitive P2X receptors enhances the pressor response seen when muscle mechanoreceptors are engaged by muscle stretch. Thus, we hypothesized that the pressor response to VR1 stimulation would be smaller and the sensitizing effects of P2X stimulation greater in rats with HF due to chronic myocardial infarction (MI) than in controls.Eight to 14 weeks after coronary ligation, rats with infarcts >35% had an increased left ventricular end-diastolic pressure and a marked increase in heart weight. Capsaicin injected into the arterial supply of the hindlimb increased blood pressure by 39% (baseline, 93.9+/-9.5 mm Hg) in control animals but only by 8% (baseline, 94.8+/-10.1 mm Hg) in rats with large MIs (P<0.05). P2X receptor stimulation by alpha,beta-methylene ATP enhanced the pressor response to muscle stretch by 42% in control animals and by 72% in rats with large MIs (P<0.05).Compared with control animals, cardiovascular responses to VR1 stimulation are blunted and P2X-mediated responses are augmented in rats with HF owing to large MIs.
Dickkopf-3 attenuates pressure overload-induced cardiac remodelling
Authors: Yan Zhang, Yu Liu, Xue-Hai Zhu, Xiao-Dong Zhang, Ding-Sheng Jiang, Zhou-Yan Bian, Xiao-Fei Zhang, Ke Chen, Xiang Wei, Lu Gao, Li-Hua Zhu, Qinglin Yang, Guo-Chang Fan, Wayne B. Lau, Xinliang Ma, Hongliang Li
Journal: Cardiovascular Research (2014)

Dickkopf-3 (DKK3), a secreted protein in the Dickkopf family, is expressed in various tissues, including the heart, and has been shown to play an important role in tissue development. However, the biological function of DKK3 in the heart remains largely unexplored. This study aimed to examine the role of DKK3 in pathological cardiac hypertrophy.We performed gain-of-function and loss-of-function studies using DKK3 cardiac-specific transgenic (TG) mice and DKK3 knockout (KO) mice (C57BL/6J background). Cardiac hypertrophy was induced by aortic banding. Cardiac hypertrophy was evaluated by echocardiographic, haemodynamic, pathological, and molecular analyses. Our results demonstrated that the loss of DKK3 exaggerated pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction, whereas the overexpression of DKK3 protected the heart against pressure overload-induced cardiac remodelling. These beneficial effects were associated with the inhibition of the ASK1-JNK/p38 (apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase/p38) signalling cascade. Parallel in vitro experiments confirmed these in vivo observations. Co-immunoprecipitation experiments suggested that physical interactions occurred between DKK3 and ASK1. Moreover, rescue experiments indicated that, in DKK3 TG mice, the activation of ASK1 using a cardiac-specific conditional ASK1 transgene reduced the functionality of DKK3 in response to pressure overload; furthermore, the inactivation of ASK1 by dominant-negative ASK1 rescued pressure overload-induced cardiac abnormalities in DKK3 KO mice.Taken together, our findings indicate that DKK3 acts as a cardioprotective regulator of pathological cardiac hypertrophy and that this function largely occurs via the regulation of ASK1-JNK/p38 signalling.
Effectiveness of CPAP Treatment in Daytime Function in Sleep Apnea Syndrome
Authors: JOSEP M. MONTSERRAT, MONTSERRAT FERRER, LOURDES HERNANDEZ, RAMÓN FARRÉ, GEMMA VILAGUT, DANIEL NAVAJAS, JOAN R. BADIA, EVA CARRASCO, JUAN DE PABLO, EUGENI BALLESTER, Marta Puig
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Application of continuous positive airway pressure (CPAP) as the standard treatment for sleep apnea/hypopnea syndrome (SAHS) is a moot point. Studies on the effectiveness of this treatment have been challenged because of the lack of a suitable placebo. The recent description of a true placebo (sham CPAP) prompted us to conduct a randomized trial of CPAP or placebo to assess the effectiveness of CPAP in improving SAHS-related symptoms and daytime function in patients with moderate to severe SAHS. Forty-eight patients, stratified in four groups according to severity, were randomly allocated into two treatment groups (optimal and sham CPAP) for a 6-wk period. Of these, 45 completed follow-up (91% males; age: 54 ± 10 yr; body mass index [BMI]: 32 ± 6 kg/m2; apnea-hypopnea index [AHI]: 54 ± 19 events/h; and Epworth Sleepiness Scale [ESS]: 16 ± 5). The ESS, a questionnaire on SAHS-related symptoms, Functional Outcomes Sleep Questionnaire (FOSQ), and the Short Form Health Survey (SF-36) were completed at inclusion and after treatment. After 10 d of washout, the placebo group was treated with optimal CPAP and reassessed before and after optimal CPAP. The group receiving optimal CPAP when compared with the group with sham CPAP showed considerably greater improvement in the relief of sleepiness ( − 9.5 versus − 2.3, p < 0.001), other SAHS-related symptoms ( − 18.5 versus − 4.5, p < 0.001), vigilance ( + 8.5 versus + 3.4, p = 0.009), and general productivity ( + 4.0 versus + 0.5, p = 0.04) FOSQ scales. Both groups used a similar number of hours for the optimal and the sham CPAP (4.3 versus 4.5, (p = NS). The patients initially treated with placebo CPAP improved significantly more when optimal CPAP was applied for ESS ( − 2.3 versus − 6.7, p < 0.001) and other sleep apnea syndrome (SAS)-related symptoms ( − 4.5 versus − 11.2, p = 0.02). Our study provides strong evidence of the effectiveness of CPAP treatment in improving symptoms and perceived health status in moderate to severe SAHS.Keywords: sleep apnea; questionnaires; positive-pressure respiration; treatment outcome; comparative study; controlled study
A 45 year old patient with headache, fever, and hyponatraemia
Authors: A. Fountas, M. Andrikoula, A. Tsatsoulis
Journal: BMJ (2015)

A 45 year old man was admitted to hospital with rapid onset headache, fever, confusion, photophobia, and hypotension. His wife confirmed a six month history of frequent headaches relieved by analgesics.

Neck stiffness was identified on clinical examination. He had no signs of water retention (ankle pitting oedema) or dehydration (dry mucous membrane, reduced skin elasticity). Initial biochemical evaluation showed raised inflammatory markers and hyponatraemia. Renal and liver function tests were within normal limits (table 1⇓).

View this table:

Table 1 
 Laboratory findings at admission 



The lumbar puncture report was diagnostic of aseptic meningitis (raised lymphocyte count with raised cerebrospinal fluid (CSF) protein and a normal CSF:plasma glucose ratio) (table 2⇓). CSF culture and Gram stain were negative for microbial infection. CSF analysis for xanthochromia was also negative.

View this table:

Table 2 
 Cerebrospinal fluid (CSF) findings at admission



Hormonal evaluation identified panhypopituitarism and magnetic resonance imaging showed a large pituitary adenoma with signs of haemorrhaging (fig 1⇓).



Fig 1 Magnetic resonance imaging of the patient showing a large pituitary adenoma with signs of haemorrhaging (arrow) 





### 1. What is the final diagnosis?

#### Short answer

Pituitary apoplexy.

#### Long answer

Pituitary apoplexy is a rare but potentially life threatening condition with an incidence of 0.6-10.5% in patients with a pituitary adenoma.1 It is usually caused by infarction or haemorrhage of the pituitary gland. In more than 80% of patients, apoplexy is the first presentation of the underlying pituitary tumour,2 so the diagnosis can be difficult and delayed. The differential diagnosis is often wide because clinical symptoms overlap with other common medical conditions, such as meningitis, meningoencephalitis, and subarachnoid haemorrhage.3

The clinical manifestations of pituitary apoplexy are the result of a rapid increase in size of the intrasellar contents, which leads to an increase in intrasellar …
Heterogeneous Expression of Interleukin-18 and Its Receptor in B-Cell Lymphoproliferative Disorders Deriving from Naive, Germinal Center, and Memory B Lymphocytes
Authors: Irma Airoldi, Lizzia Raffaghello, Claudia Cocco, Roberta Guglielmino, Silvio Roncella, Franco Fedeli, Claudio Gambini, Vito Pistoia
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Dysregulated cytokine/cytokine receptor expression may occur in B-cell lymphoproliferative disorders. Little information is available on interleukin-18 receptor (IL-18R) and IL-18 expression in normal and malignant B cells. Our purpose was to investigate this issue in human naive, germinal center (GC) and memory B cells, and in their neoplastic counterparts. Experimental Design: We have evaluated IL-18 expression and production in tonsil naive, GC, and memory B cells and in their presumed neoplastic counterparts by reverse transcription-PCR and ELISA. Moreover, IL-18Rα and β expression was investigated in the same cells by reverse transcription-PCR, flow cytometry, and immunohistochemistry. Results: We found that: (a) IL-18 mRNA was expressed in tonsil naive, GC, and memory B cells. Bioactive IL-18 was secreted by naive and GC, but not by memory B cells; (b) IL-18Rα and β transcripts were expressed in the three B-cell subsets. IL-18Rα was detected on the surface of naive, GC, and memory B lymphocytes, and IL-18Rβ was detected on GC and memory, but not naive, B cells; (c) mantle zone, follicular, marginal zone, Burkitt lymphoma (BL), and B-cell chronic lymphocytic leukemia (B-CLL) cells expressed IL-18 mRNA. B-CLL and BL cells did not produce bioactive IL-18; and (d) lymphoma B cells displayed heterogeneous expression of either or both IL-18R chain mRNA. In contrast, B-CLL cells expressed both IL-18R chains at the mRNA and protein levels. Conclusions: Dysregulated expression of IL-18 and/or IL-18R in chronic B-cell lymphoproliferative disorders may sometimes contribute to tumor escape from the host immune system.