tbuckley/cabot-search huggingface dataset:
Coagulation Factor Xa Modulates Airway Remodeling in a Murine Model of Asthma
Authors: Kazuhiko Shinagawa, J. Andrew Martin, Victoria A. Ploplis, Francis J. Castellino
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Previous studies have demonstrated that dysregulated coagulation and fibrinolysis contribute to the pathogenesis of asthma.The role of procoagulant factor X in a murine model of ovalbumin (OVA)-induced asthma was investigated.Biochemical, cellular, and physiologic in vivo and in vitro approaches were used to determine effects of factor X on the asthmatic response in mice.Factor X transcript levels and factor Xa activity were increased in lungs of asthmatic mice challenged with OVA, compared with controls treated with phosphate-buffered saline. Factor X was highly expressed in bronchoalveolar lavage fluid macrophages from asthmatic mice. Treatment of mice with the factor Xa inhibitor fondaparinux during the last 4 wk of OVA challenge resulted in the attenuation of airway hyperresponsiveness but did not alter infiltration of inflammatory cells into the lung. There was a significant decrease in the thickness of the mucosal layer and in lung collagen deposition in fondaparinux-treated mice. In vitro investigations using human mucus-producing NCI-H292 cells indicated that exogenous factor Xa enhanced mucin production in a dose-dependent manner. Levels of amphiregulin, a protein that induces mucin production, were also increased in cells stimulated by factor Xa.The results of this study introduce a novel participant in the asthmatic response and indicate that factor Xa functions in airway remodeling in asthma by stimulating mucin production, through regulation of amphiregulin expression and collagen deposition.
Reply to A. Jiménez-Velasco et al
Authors: Michele Baccarani
Journal: Journal of Clinical Oncology (2010)

We appreciate the interest of Jimenez-Velasco et al in the newly revised edition of the European LeukemiaNet chronic myeloid leukemia (CML) recommendations. They noticed we recommended performing the first cytogenetic test at 3 months, and in the case of no cytogenetic response (Ph 95%) we defined the response as suboptimal. In the case of at least a minor cytogenetic response (Ph 65), we defined the response as optimal, but we did not make any recommendation for minimal cytogenetic response (Ph 66% to 95%). As also reported by Jimenez-Velasco et al in their letter, the data pertaining to the prognostic value of the cytogenetic response at 3 months are limited. We reviewed the studies already published, and we also considered some unpublished data from the GIMEMA CML Study Group. We believe that although it is possible to attribute a suboptimal value to the minimal cytogenetic response, the data were insufficient to validate this recommendation. In conclusion, it was possible to express a clinically and therapeutically relevant recommendation either for Ph less than 65% (optimal) or Ph more than 95% (suboptimal), but not for Ph 66% to 95%. In such cases, the current recommendation is to continue the treatment, even if the response does not fit the definition of optimal.
Easy assessment of the biocompatibility of Ni–Ti alloys by in vitro cell culture experiments on a functionally graded Ni–NiTi–Ti material
Authors: Denise Bogdanski, Manfred Köller, Dietmar Müller, Gert Muhr, Martin Bram, Hans Peter Buchkremer, Detlev Stöver, Jongsik Choi, Matthias Epple
Journal: Biomaterials (2002)
Hawaiian Health Plan: Less Than Meets the Eye?
Authors: Donald B. Louria
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Hawaii adopted an employer mandate in 1974 as the Prepaid Health Care Act, and according to a May 19 article in JAMA,<sup>1</sup>this is responsible for reduced health care costs and better health indexes, including far fewer productive years lost. Drs Lewin and Sybinsky indicate that in Hawaii the emphasis is on ready access and outpatient care. They suggest the Hawaiian program be adopted nationally. All this may be true, but is the hypothesis adequately documented? The following should be noted: A lower breast cancer death rate is frequently cited, but according to a Centers for Disease Control and Prevention (CDC)2 publication, in 1979, breast cancer deaths in Hawaii were 40% lower than the rest of the United States. The Hawaii employer mandate was started in 1974 and implemented primarily in the 1980s and therefore could not account for the lower rate. Furthermore, if early intervention
Tumor Necrosis Factor (TNF)-alpha Down-Regulates Loricrin and Involucrin
Authors: B.E. Kim, D.Y.M. Leung, M. Boguniewicz, M.D. Howell
Journal: Journal of Allergy and Clinical Immunology (2010)

RATIONALE: Patients with atopic dermatitis (AD) and psoriasis are characterized by an impaired skin barrier. The skin of AD patients is characterized by the over-expression of Th2 cytokines, which have been shown to down-regulate the barrier genes loricrin and filaggrin. In contrast, the psoriasis skin is characterized by Th1 cytokines. Therefore we investigated filaggrin and loricrin expression in psoriasis skin and whether Th1 cytokines modulate barrier genes. METHODS: Skin biopsies were collected from healthy subjects (n=10), patients with chronic AD (n=7), and psoriasis (n=10). Filaggrin, loricrin and TNF-α gene expression was measured in skin biopsies and primary human keratinocytes using real-time RT-PCR. RESULTS: Filaggrin and loricrin gene expression was significantly decreased (p<0.01) in skin from chronic AD patients (filaggrin: 15.99 ± 4.49 ng; loricrin: 83.76 ± 49.65 ng) and psoriasis patients (mean: 7.99 ± 2.00 ng; loricrin: 48.77 ± 8.24 ng), as compared to skin from healthy subjects (filaggrin: 45.06 ± 7.78 ng; loricrin: 296.69 ± 54.67 ng). TNF-alpha is elevated in the skin of chronic AD and psoriasis patients. We therefore examined the effects of TNF-alpha on keratinocyte expression of skin barrier proteins. TNF-alpha significantly reduced filaggrin (p<0.05) and loricrin expression (p<0.05) compared to media alone. Pre-treating keratinocytes with a neutralizing antibody blocked the TNF-alpha-mediated inhibition of filaggrin and loricrin. CONCLUSIONS: Our data suggests that TNF-alpha down-regulates loricrin and filaggrin expression and may account for barrier disruption in chronic AD and psoriatic skin.
More marketing than science
Authors: F. Godlee,
Journal: BMJ (2012)

The lessons from this week’s Patient Journey are a bit old fashioned, says Mark Weatherall, the neurologist who managed Joyce Dobson’s care when she developed facial palsy, double vision, and unsteadiness in her late 70s. “Cast your differential diagnosis wide,” he writes, “don’t dismiss results that don’t fit your diagnosis; many brains are better than one (even a neurologist); and the answer, more often than not, lies in the history.” The answer in this case was Lyme neuroborreliosis, contracted while the patient was on holiday in southern France (doi:10.1136/bmj.e3250).

Despite alarming symptoms and some continuing troubling sequelae, the outcome for this patient was largely good. …
Clinicians’ Perceptions of the Value of Ventilation-Perfusion Scans
Authors: Alan Siegel, Stephen R. Holtzman, Michael A. Bettmann, William C. Black
Journal: Clinical Nuclear Medicine (2004)

The goal of this investigation was to understand clinicians' perceptions of the probability of pulmonary embolism as a function of V/Q scan results of normal, low, intermediate, and high probability.A questionnaire was developed and distributed to 429 clinicians at a single academic medical center. The response rate was 44% (188 of 429). The questions included level of training, specialty, probability of PE given 1 of the 4 V/Q scan results, and estimations of the charges for V/Q scanning and pulmonary angiography, and estimations of the risks of pulmonary angiography.The medians and ranges for the probability of pulmonary embolism given a normal, low, intermediate, and high probability V/Q scan result were 2.5% (0-30), 12.5% (0.5-52.5), 41.25% (5-75), and 85% (5-100), respectively. Eleven percent (21 of 188) of the respondents listed the probability of PE in patients with a low probability V/Q scan as being 5% or less, and 33% (62 of 188) listed the probability of PE given an intermediate probability scan as 50% or greater. The majority correctly identified the rate of serious complications of pulmonary arteriography, but many respondents underestimated the charge for V/Q scans and pulmonary arteriography.A substantial minority of clinicians do not understand the probability of pulmonary embolism in patients with low and intermediate probability ventilation-perfusion scans. More quantitative reporting of results is recommended. This could be particularly important because VQ scans are used less frequently but are still needed in certain clinical situations.
"When are you Going to Stop Beating Your Wife, Mr. Commissioner?"
Authors: Robert H. Moser
Journal: JAMA (1974)

I dislike bully-boy tactics, and last month I witnessed a prize exhibition. It was all quite unanticipated. I heard that the FDA was being called on to respond to allegations of "drug lag." (Does the United States lag behind England in the availability of effective, safe, new drugs?) I was interested in the FDA response, because it is a key issue in whichThe Journalhas taken keen interest. Recent communications by Freis, Wardell, and Lasagna have reflected our concern that the FDA (in its zeal to comply with the 1962 Kefauver mandates) perhaps has been overly cautious in releasing new drugs that have been proven safe and effective in England, to the American physician. In response to this, Commissioner Schmidt has said, "We believe we have done much in recent years to recognize and correct problems in our own house which have contributed unnecessarily to delaying decision-making on new
Immune response to bacterial dextrans. II. T cell control of antibody isotypes.
Authors: F Ivars, G Nyberg, D Holmberg, A Coutinho
Journal: The Journal of Experimental Medicine (1983)

The isotype distribution of Dextran B 512 (Dex)-specific plaque-forming cells (PFC) and serum antibodies was studied after in vivo immunization in C57BL/6 mice. Although IgG2b and IgG3 could also be detected in most individuals, the majority of non-IgM PFC were of the IgA isotype. All classes other than IgM were T cell-dependent, as shown by their complete absence in athymic "nude" mice. This unusual isotype pattern was further investigated by studying the antibody responses to the same Dex epitope coupled to a protein carrier, and to a different hapten coupled to the carrier Dex or to a protein. The results show that IgA responses are epitope-related and selectively associated with anti-Dex antibodies: no IgA PFC are detected against a hapten coupled to Dex or proteins, while the enhanced levels of helper cell reactivity provided by protein carrier to Dex result in the appearance of IgG1 antibodies in addition to IgA. These results indicate that T cells that modulate isotype patterns in these responses can discriminate between Dex- and DNP-specific B cells in the response to the same carrier. Since the same idiotype is detected on a large fraction of the IgM and IgA anti-Dex response and antiidiotypic helper cells have previously been detected in normal C57BL/6 mice, we suggest that idiotype-specific T cells control the production of IgA antibodies upon immunization with Dex.
Abstract 558: Constitutive activation of p38 MAPK signaling in tumor cells induces osteolytic bone lesions via regulating bone marrow microenvironment
Authors: Jing Yang, Qing Yi
Journal: Cancer Research (2010)

Abstract Bone residing tumor cells cause osteolysis, characterized with severe bone pain, multiple fractures and hypercalcemia in patients. While it has been proposed that tumor cells activate osteoclasts and/or inhibit osteoblasts, leading to bone resorption, the mechanism underlying tumor-induced osteoclastogenesis activation in bone marrow microenvironment, which causes osteolytic bone lesions, is yet to be elucidated. P38 mitogen-activated protein kinase (MAPK) is commonly constitutively activated in malignant osteolytic tumors. We hypothesize that constitutive activity of p38 MAPK in tumor cells might contribute to osteolytic bone lesions via regulating bone marrow microenvironment. For this purpose, we applied of small hairpin RNAs (shRNAs) to disrupt p38 MAPK activity in myeloma ARP-1 and bone metastatic breast cancer MDA-MB-231 cells. To evaluate the role of tumor p38 MAPK in bone lesions, tumor cells with p38 MAPK-shRNAs or control vectors were intravenously injected to SCID mice. Lytic lesions in tibial bones were measured by radiograph and μ-CT, and further confirmed by histological examination. The results showed that lytic bone lesions were found in mice bearing of tumor cells with control vectors. In contrast, no or less bone lesions were found in mice with shRNA-expressing tumor cells. Moreover, decrease of osteoclast amounts covered bone surface, as well as circulating levels of collagen type I (bone resorption marker) and TRAP5b (active osteoclast marker), but increase of osteoblast amounts, and osteocalcin (bone formation marker) and ALP (active osteoblast marker), were found in those mice injected with shRNA-tumor cells. Noticeably, tumor p38 MAPK enhanced osteoclast differentiation and activity, as well as inhibited osteoblast maturation and function in vitro. However, disruption of p38 MAPK activity in tumor cells did not affect tumor growth and tumor cell homing to bone. We further identified that tumor p38 MAPK-derived monocyte chemotactic protein-1 (MCP-1) and dickkopf-1 (DKK-1) induced bone lesions via activation of RANK/RANKL-mediated NFκB, p38 MAPK and ERK1/2 signaling pathways. In conclusion, our results elucidate a novel mechanism that tumor p38 MAPK activity regulates bone marrow microenvironment and contributes to tumor-induced osteolytic bone lesions. Thus, inhibition of p38 MAPK signaling in tumor cells may have an important implication to treat bone lesions in patients with osteolytic tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 558.
GEOGRAPHIC VARIATION OF LOWER EXTREMITY AMPUTATION IN PATIENTS WITH PERIPHERAL ARTERY DISEASE: RESULTS FROM U.S. MEDICARE 2000-2008
Authors: William Schuyler Jones, Manesh Patel, Dadi (David) Dai, Sumeet Subherwal, Judith Stafford, Sarah Calhoun, Eric Peterson
Journal: Journal of the American College of Cardiology (2012)
Hemoglobin Abraham Lincoln, β32 (B14) Leucine → Proline AN UNSTABLE VARIANT PRODUCING SEVERE HEMOLYTIC DISEASE
Authors: George R. Honig, David Green, Mir Shamsuddin, Loyda N. Vida, R. George Mason, David J. Gnarra, Helen S. Maurer
Journal: Journal of Clinical Investigation (1973)

An unstable hemoglobin variant was identified in a Negro woman with hemolytic anemia since infancy. A splenectomy had been performed when the patient was a child. The anemia was accompanied by erythrocyte inclusion bodies and excretion of darkly pigmented urine. Neither parent of the proposita demonstrated any hematologic abnormality, and it appeared that this hemoglobin variant arose as a new mutation. Erythrocyte survival in the patient was greatly reduced: the erythrocyte t(1/2) using radiochromium as a tag was 2.4 days, and a reticulocyte survival study performed after labeling the cells with L-[(14)C]leucine indicated a t(1/2) of 7.2 days. When stroma-free hemolysates were heated at 50 degrees C, 16-20% of the hemoglobin precipitated. The thermolability was prevented by the addition of hemin, carbon monoxide, or dithionite, suggesting an abnormality of heme binding. An increased rate of methemoglobin formation was also observed after incubation of erythrocytes at 37 degrees C. The abnormal hemoglobin could not be separated from hemoglobin A by electrophoresis or chromatography, but it was possible to isolate the variant beta-chain by precipitation with p-hydroxymercuribenzoate. Purification of the beta-chain by column chromatography followed by peptide mapping and amino acid analysis demonstrated a substitution of proline for beta32 leucine. It appears likely that a major effect of this substitution is a disruption of the normal orientation of the adjacent leucine residue at beta31 to impair heme stabilization.
Cellular Telephones and Brain Tumors
Authors: Dimitrios Trichopoulos, Hans-Olov Adami
Journal: New England Journal of Medicine (2001)

Cellular telephones are low-power radio devices that transmit and receive electromagnetic radiation at frequencies of about 1000 MHz, just above the ultrahigh-frequency (UHF) television portion and just below the microwave part of the electromagnetic spectrum. These three frequency ranges are within the radio-frequency zone of that spectrum. Cellular telephones operate at a lower power (less than 1 watt) than police or other emergency-communication devices. Cordless telephones, which have a base unit that is wired to a conventional telephone service, operate at a lower frequency and power than cellular telephones; they cannot be classified as a type of cellular telephone.1, . . .
Isolation of spheroplastic forms of Haemophilus influenzae from sputum in conventionally treated chronic bronchial sepsis using selective medium supplemented with N-acetyl-D-glucosamine: possible reservoir for re-emergence of infection.
Authors: D Roberts, E Higgs, A Rutman, P Cole
Journal: BMJ (1984)

The isolation rate of Haemophilus influenzae from patients with persistent production of purulent sputum has been increased by the routine use of a selective medium. Nevertheless, some purulent sputum still fails to yield a pathogen. The selective medium was supplemented with N-acetyl-D-glucosamine to encourage primary isolation of colony forming, spheroplastic H influenzae, which reverted to normal forms on subculture. On the basis of in vitro experiments it is postulated that these spheroplastic forms of H influenzae may be induced by inadequate antimicrobial chemotherapy and may be responsible for re-emergence of symptoms in these patients during or shortly after stopping chemotherapy.
First- and second-line therapy for advanced nonsmall cell lung cancer
Authors: J-P. Sculier, D. Moro-Sibilot
Journal: European Respiratory Journal (2009)

The objectives for the treatment of advanced nonsmall cell lung cancer are palliative and include improvement of survival, symptom control, quality of life and cost. The level of evidence of these benefits is based on multiple randomised trials and meta-analyses. Cisplatin-based chemotherapy with one of the regimens shown to be effective should be preferred. Carboplatin may be substituted for cisplatin if medical contraindications exist. Nonplatinum-based regimens are indicated as first-line treatment for advanced nonsmall cell lung cancer in patients for whom platinum-based chemotherapy is contraindicated. Single drug chemotherapy may be considered in patients with poor performance status. The choice of the active drugs depends on the patient's medical condition. There is no conclusive evidence that high doses of cisplatin (100–120 mg·m −2 ) provide better results than standard lower doses (50–60 mg·m −2 ) in terms of survival. The optimal duration of chemotherapy is poorly documented in advanced nonsmall cell lung cancer. A minimum of four to six cycles is advised in responding patients. Second-line chemotherapy is now accepted as a standard and should be offered to patients with good performance status and failing platinum-based first-line chemotherapy. Evidence is in favour of docetaxel and in the case of adenocarcinoma and adequate renal function, pemetrexed is recommended.
Touched by greatness
Authors: S Spence
Journal: BMJ (1994)

Glenn Gould, the Canadian virtuoso pianist, died from a stroke in 1982 at the age of 50. He was renowned as much for his eccentricities as his talent. This visually striking film takes a kaleidoscopic approach to Gould's life. He emerges as a genius with crippling flaws that were ultimately to isolate him. The title is a reference to Bach's 32 Goldberg Variations, recorded by Gould when he was 23.

Even then the seeds of his undoing were apparent. He attended recording sessions in layers of jumpers, gloves, scarves, and a heavy coat. He shunned being touched by others, gave interviews by telephone, and eventually retired from live performance at the age of …
Conference urges better housing for better health
Authors: C Court
Journal: BMJ (1994)

<h3>Objective</h3> To evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) as an adjunct to endovascular thrombectomy (EVT) in ischemic stroke, we performed a systematic review and meta-analysis of the literature. <h3>Methods</h3> Searches were performed using MEDLINE, Embase, and Cochrane databases for studies that compared EVT with EVT with adjunctive IAT (EVT + IAT). Safety outcomes included symptomatic intracerebral hemorrhage and mortality at 3 months. Efficacy outcomes included successful reperfusion (Thrombolysis in Cerebral Infarction score of 2b–3) and functional independence, defined as a modified Rankin Scale score of 0–2 at 3 months. <h3>Results</h3> Five studies were identified that compared combined EVT + IAT (IA alteplase or urokinase) with EVT only and were included in the random-effects meta-analysis. There were 1693 EVT patients, including 269 patients treated with combined EVT + IAT and 1,424 patients receiving EVT only. Pooled analysis did not demonstrate any differences between EVT + IAT and EVT only in rates of symptomatic intracerebral hemorrhage (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.20–1.85; <i>p</i> = 0.78), mortality (OR: 0.77, 95% CI: 0.54–1.10; <i>p</i> = 0.15), or successful reperfusion (OR: 1.05, 95% CI: 0.52–2.15; <i>p</i> = 0.89). There was a higher rate of functional independence in patients treated with EVT + IAT, although this was not statistically significant (OR: 1.34, 95% CI: 1.00–1.80; <i>p</i> = 0.053). <h3>Conclusion</h3> Adjunctive IAT appears to be safe. In specific situations, neurointerventionists may be justified in administering small doses of intra-arterial alteplase or urokinase as rescue therapy during EVT.