tbuckley/cabot-search huggingface dataset:
Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation
Authors: Sébastien Conus, Remo Perozzo, Thomas Reinheckel, Christoph Peters, Leonardo Scapozza, Shida Yousefi, Hans-Uwe Simon
Journal: The Journal of Experimental Medicine (2008)

In the resolution of inflammatory responses, neutrophils rapidly undergo apoptosis. We describe a new proapoptotic pathway in which cathepsin D directly activates caspase-8. Cathepsin D is released from azurophilic granules in neutrophils in a caspase-independent but reactive oxygen species–dependent manner. Under inflammatory conditions, the translocation of cathepsin D in the cytosol is blocked. Pharmacological or genetic inhibition of cathepsin D resulted in delayed caspase activation and reduced neutrophil apoptosis. Cathepsin D deficiency or lack of its translocation in the cytosol prolongs innate immune responses in experimental bacterial infection and in septic shock. Thus, we identified a new function of azurophilic granules that is in addition to their role in bacterial defense mechanisms: to regulate the life span of neutrophils and, therefore, the duration of innate immune responses through the release of cathepsin D.
Large lung bullae in sarcoidosis.
Authors: G E Packe, J G Ayres, K M Citron, D E Stableforth
Journal: Thorax (1986)

Large lung bullae are a rare manifestation of pulmonary sarcoidosis. Of three patients with this complication, all had pulmonary infiltrates at presentation and two had bilateral hilar adenopathy. Hypercalcaemia developed during the course of the illness in all three patients. In each case the bullae had developed within four years of the diagnosis of sarcoidosis. In one woman a bulla resolved almost completely after it had become infected.
Reduced risk of distant recurrence after adjuvant chemotherapy in patients with stage III colon cancer aged 75 years or older
Authors: F.N. van Erning, G.J. Creemers, I.H.J.T. De Hingh, O.J.L. Loosveld, S.H. Goey, V.E.P.P. Lemmens
Journal: Annals of Oncology (2013)
Hell is the paediatric fracture clinic
Authors: Virginia Davies
Journal: BMJ (2005)

F or the first few weeks it was fine. My daughter and I would get to the clinic as it started, get the x ray picture taken, nip back downstairs, pass before the eyes of the orthopod, and get out. All achieved in approximately one hour.

Then it started to go wrong. Booking a fortnight in advance, I asked the receptionist for the earliest possible appointment. I'm sure she told me we'd got a 9 30 am slot, but when the computer generated outpatient appointment letter (complete with mission statement on the back) arrived a week later, my daughter's appointment time was given as 10 30 am. Never mind, I thought, we'll just turn up early and get in and out like we normally do.

So off we set at 8 am to get the bus—parking is expensive and the underground station is miles away. It was all quite exciting really, my 6 year old watching …
The epidemiology of interstitial lung diseases.
Authors: D B Coultas, R E Zumwalt, W C Black, R E Sobonya
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Little epidemiologic data are available on the occurrence of interstitial lung diseases (ILDs) in the general population. To describe the prevalence and incidence of ILDs a population-based registry of patients with ILDs was established in Bernalillo County, New Mexico in October 1988. All patients 18 yr of age and older who had a clinical diagnosis of an ILD were identified during the period 10/1/88 through 9/30/90 from physician referrals, hospital discharge diagnoses, histopathology reports, and death certificates. In addition, the prevalence of preclinical or undiagnosed cases was identified by screening lung specimens from 510 autopsy cases. A total of 2,936 referrals were screened; 8.8% were prevalent cases and 6.9% were incident cases. Overall, the prevalence of ILDs was 20% higher in males (80.9 per 100,000) than in females (67.2 per 100,000). Similarly the overall incidence of ILDs was slightly more common in males (31.5 per 100,000/year) than females (26.1 per 100,000/year). The estimated prevalence of preclinical or undiagnosed ILDs among all deaths was 1.8%. The most common incident diagnosed among both sexes were pulmonary fibrosis and idiopathic pulmonary fibrosis, together accounting for 46.2% of all ILD diagnoses in males and 44.2% in females. We conclude that the occurrence of ILDs in the general population may be more common than previous estimates based on selected populations, and these disorders may frequently be unrecognized.
Abnormal systolic blood pressure response during exercise is related to subendocardial hypoperfusion detected by exercise 201 Tl myocardial scintigraphy in patient with hypertrophic cardiomyopathy
Authors: N. Yoshida, H. Ikeda, T. Wada, S. Maki, A. Matsumoto, E. Sumida, T. Imaizumi
Journal: Journal of the American College of Cardiology (1998)
Mast cell density in isolated monkey lungs on exposure to cigarette smoke.
Authors: A Walter, S Walter
Journal: Thorax (1982)

The density and percentage of degranulated cells of the mast cell population were studied in the isolated lungs of 25 monkeys (Macaca radiata radiata) before and after acute exposure to cigarette smoke. In each animal one lung was used as the test lung while the other lung was used as its control. In the control lungs the total mean mast cell count was 9.5/mm2 and the proportion of degranulated cells was 9.7%. In the lungs exposed to smoke the total counts were lower (7.3/mm2) and the percentage of degranulated cells higher (15.8%). These differences were statistically significant (p less than 0.01) and show that after acute exposure to cigarette smoke there is a degranulation of lung mast cells. Since degranulation is accompanied by local release of histamine, which could act on the smooth muscle of the airways, it is suggested that this may be a mechanism by which smoking-induced acute bronchoconstriction is mediated.
Vaccination of Small Cell Lung Cancer Patients with Polysialic Acid or<i>N</i>-Propionylated Polysialic Acid Conjugated to Keyhole Limpet Hemocyanin
Authors: Lee M. Krug, Govind Ragupathi, Kenneth K. Ng, Chandra Hood, Harold J. Jennings, Zhongwu Guo, Mark G. Kris, Vincent Miller, Barbara Pizzo, Leslie Tyson, Valerie Baez, Philip O. Livingston
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Long chain polysialic acid (polySA) is a side chain on embryonal neural cell adhesion molecules that, in the adult, is largely restricted to small cell lung cancer (SCLC). Long chains of polySA are also expressed on group B meningococcus. In this clinical trial, we aimed to elicit an immune response against polysialic acid to target clinically inapparent residual disease in patients with SCLC who had successfully completed initial therapy. Experimental Design: Patients were vaccinated with either 30 μg unmodified polySA or N-propionylated-polySA (NP-polySA), conjugated to keyhole limpet hemocyanin (KLH) and mixed with 100 μg of immunological adjuvant QS-21 at weeks 1, 2, 3, 4, 8, and 16. Results: Of the 5 evaluable patients vaccinated with unmodified polySA, only 1 mounted an IgM antibody response to polySA. On the other hand, all 6 of the patients vaccinated with NP-polySA produced IgM antibodies to NP-polySA and these cross-reacted with unmodified polySA in all but 1 case. IgG antibodies to NP-polySA were observed in 5 of the patients, but these did not cross-react with polySA. The presence of IgM antibodies reactive with SCLC cell lines was confirmed in this group by flow cytometry. Complement-dependent lysis of tumor cells could not be demonstrated. However, postimmunization sera induced significant bactericidal activity against group B meningococcus when combined with rabbit complement. Conclusions: Vaccination with NP-polySA-KLH, but not polySA-KLH, resulted in a consistent high titer antibody response. We are now conducting a de-escalation dosing study with NP-polySA-KLH to better assess the immunogenicity, toxicities, and optimal dose of this vaccine. We plan to incorporate this vaccine as a component of a polyvalent vaccine with GM2, fucosylated GM1, and Globo H to target SCLC.
Preliminary Results of the Safety of Immunotherapy with Gemtuzumab Ozogamicin following Reduced Intensity Allogeneic Stem Cell Transplant in Children with CD33+ Acute Myeloid Leukemia
Authors: Elizabeth Roman, Erin Cooney, Lauren Harrison, Olga Militano, Karen Wolownik, Ria Hawks, Sandi Foley, Prakash Satwani, Elif Unal, Monica Bhatia, Brigid Bradley, Gustavo Del Toro, Diane George, James Garvin, Carmella van de Ven, Mitchell S. Cairo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Myeloablative allogeneic stem cell transplantation (SCT) has been successful in the treatment of childhood acute myeloid leukemia (AML), but may be associated with significant toxicity and recurrent disease. Reduced-intensity allogeneic SCT may offer a less toxic approach to patients with AML. Targeted immunotherapy with gemtuzumab ozogamicin has been shown to be safe, well tolerated in children, and, as a single agent, gemtuzumab ozogamicin has induced responses in 30% of patients with recurrent CD33+ AML. There are no safety data with gemtuzumab ozogamicin post allogeneic SCT in children. Therefore, we explored the feasibility and toxicity of targeted immunotherapy following reduced-intensity allogeneic SCT in children with CD33+ AML. Experimental Design: Eight patients with CD33+ AML received a reduced-intensity allogeneic SCT following fludarabine 30 mg/m2 for 6 days and busulfan 3.2 mg/kg (&amp;lt;4 years, 4 mg/kg/d) for 2 days. Donor sources included six 6/6 HLA-matched related peripheral blood stem cells, one 6/6 sibling cord blood, and one 4/6 unrelated cord blood. Results: Day 30 and day 60 donor chimerisms in seven of eight evaluable patients were 96 ± 2% (n = 7) and 94 ± 3% (n = 6), respectively. Five of six patients (too early for one patient) received two doses of gemtuzumab ozogamicin and one patient received only one dose. After each dose, all patients developed grade 4 neutropenia, with recovery on median days 16 and 13, respectively, after dose 1 and dose 2. Grade 4 thrombocytopenia was only observed in 2 of 11 gemtuzumab ozogamicin courses. No patients have developed dose-limiting toxicity secondary to gemtuzumab ozogamicin. Conclusions: The administration of gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with average risk AML is feasible and well tolerated with minimal toxicity. The maximal tolerated dose has yet to be determined for gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with CD33+ AML. Additional studies in a larger group of patients will be required to adequately assess the safety of this approach.
Regional ventilation and gas exchange after hemicorporectomy
Authors: B. Bake, G. Grimby
Journal: Thorax (1974)

<b>Bake, B. and Grimby, G. (1974).</b><i>Thorax</i>, <b>29</b>, 366-370. <b>Regional ventilation and gas exchange after hemicorporectomy.</b> Maximum expiratory flow volume curves, gas exchange, closing volume, and regional distribution of lung volumes and ventilation were measured in a young man after hemicorporectomy. The patient breathed at low lung volume, close to residual volume, and his total lung capacity was 63% of predicted normal. Maximum expiratory flows were normal at comparable lung volumes but the alveolo-arterial oxygen difference was increased at rest and during exercise. Closing volume exceeded functional residual capacity but was below predicted normal. Basal regions of the lungs were relatively hypoventilated and overexpanded. Most of these findings are probably due to the low breathing mid-position and possibly also to other effects of altered abdominal mechanics.
Polyclonal Immunoglobulin Free Light Chain Levels Predict Survival in Myeloid Neoplasms
Authors: Animesh Pardanani, Terra L. Lasho, Christy M. Finke, S. Vincent Rajkumar, Preet Paul Singh, Rhett P. Ketterling, Curtis A. Hanson, Jerry A. Katzmann, Ayalew Tefferi
Journal: Journal of Clinical Oncology (2012)

We hypothesized that surrogate markers of host immune response may predict survival in myeloid malignancies. Because of immediate practical applicability, we chose plasma immunoglobulin free light chain (FLC) concentration as the biomarker of interest.Two independent cohorts of patients with primary myelofibrosis (PMF) or myelodysplastic syndromes (MDS) were studied. Kappa (κ) and lambda (λ) FLCs were measured by a quantitative nephelometric assay. Patients with monoclonal FLC were excluded.Values that were above the upper limit of normal for κ or λ FLC were documented in 33% of 240 patients with PMF and 46% of 74 patients with MDS. Increased FLC was significantly associated with increased creatinine, and advanced age in PMF (P < .001) and hemoglobin less than 10 g/dL in MDS (P = .005). In multivariable analysis, increased FLC predicted shortened survival in both PMF and MDS, independent of age, creatinine, and other conventional risk factors. Cutoff levels based on receiver operating characteristic analysis for κ plus λ total FLCs delineated risk groups with highly significant differences in overall survival; International Prognostic Scoring System-adjusted hazard ratio in PMF was 1.9 (95% CI, 1.3 to 2.7), and was 6.3 (95% CI, 2.7 to 16.6) in MDS. No correlations were seen with leukemia-free survival, karyotype, or JAK2, MPL, or IDH mutations. In patients with PMF who were studied by cytokine profiling, the prognostic value of an increased FLC level was independent of that from circulating interleukin-2 receptor (IL-2R) or IL-8 levels.Increased plasma FLC concentration predicts inferior survival in both PMF and MDS. Its lack of correlation with leukemia-free survival and tumor-specific genetic markers suggests a primarily host-driven biologic phenomenon that might be more broadly applicable.
mTOR Pathway as a Target in Tissue Hypertrophy
Authors: Chung-Han Lee, Ken Inoki, Kun-Liang Guan
Journal: The Annual Review of Pharmacology and Toxicology (2006)

Recent work has shown that the mTOR (mammalian target of rapamycin) pathway is an integral cell growth regulator. The mTOR pathway involves two functional complexes, TORC1 and TORC2, which have been defined by both their association with raptor or rictor, respectively, and their sensitivity to short-term rapamycin inhibition. Loss of tumor suppressors TSC1 or TSC2 leads to aberrant activation of TORC1, which has been implicated in the control of cell size. As a result, both physiologic and pathologic tissue hypertrophy are associated with TORC1 activation. Some clinical examples include skeletal and cardiac muscle hypertrophy, vascular restenosis, and compensatory nephrotic hypertrophy. Clarification of the mTOR pathway may lead to increased understanding of both the etiology and consequences of aberrant cell size regulation. This review covers some of the biochemical regulation of the mTOR pathway that may be important to the regulation of cell size, and it will present several potential clinical applications where the control of cell size may be biologically significant.
Scrub Typhus Vaccine
Authors: W. T. Walker
Journal: BMJ (1947)

he had fully recovered.Since that date he had been well except for occasional conjunctivitis and a very slight urethral discharge.There was no previous history of dysentery or venereal disease other than the above.On Aug. 13 he sought advice on account of a slight urethral discharge of one week's duration.A smear showed pus cells but no gonococci; he was given sulphathiazole 5 g.daily for five days.On the following day he fell and injured his left knee.When he returned on Aug. 20 he showed an improvement in the urethral discharge, but a marked effusion was present in the left knee; moreover, there was a severe bilateral conjunctivitis of two days' and a balanitis of six weeks' duration.He was admitted to hospital and given 200.000 units of penicillin in five three-hourly doses of 40,000 units.On the 21st his urethral smear continued to show many pus cells, while the urine was hazy in two glasses.The blood Wassermann and Kahn tests and the gonococcal complement-fixation test were negative; blood count: haemoglobin, 115% ; red cells, 5,490,000; white cells, 10,600; polymorphs 61 %, lymphocytes 35%, mononuclears 4%; urine: albumin, sugar, ketones, bile negative; stool: no pathogens found in culture; blood sedimen- tation rate, 6 mm. in 1 hour.A skiagram of the knee revealed no bone injury.On the following day urethral and conjunctival smears were taken for special examination and the left knee was aspirated.Gold therapy with myocrisin was then begun.Temperature recordings, daily urine examination for albumin, and skin inspection and blood counts twice a week did not reveal any toxic reactions.The dates and amounts of the myocrisin, together with the relevant sedimentation rates, are as follows:
Genome-Wide Profiling of CpG Methylation Identifies Novel Targets of Aberrant Hypermethylation in Myeloid Leukemia
Authors: Claudia Gebhard, Lucia Schwarzfischer, Thu-Hang Pham, Elmar Schilling, Maja Klug, Reinhard Andreesen, Michael Rehli
Journal: Cancer Research (2006)

The methylation of CpG islands is associated with transcriptional repression and, in cancer, leads to the abnormal silencing of tumor suppressor genes. Because aberrant hypermethylation may be used as a marker for disease, a sensitive method for the global detection of DNA methylation events is of particular importance. We describe a novel and robust technique, called methyl-CpG immunoprecipitation, which allows the unbiased genome-wide profiling of CpG methylation in limited DNA samples. The approach is based on a recombinant, antibody-like protein that efficiently binds native CpG-methylated DNA. In combination with CpG island microarrays, the technique was used to identify >100 genes with aberrantly methylated CpG islands in three myeloid leukemia cell lines. Interestingly, within all hypermethylation targets, genes involved in transcriptional regulation were significantly overrepresented. More than half of the identified genes were absent in microarray expression studies in either leukemia or normal monocytes, indicating that hypermethylation in cancer may be largely independent of the transcriptional status of the affected gene. Most individually tested genes were also hypermethylated in primary blast cells from acute myeloid leukemia patients, suggesting that our approach can identify novel potential disease markers. The technique may prove useful for genome-wide comparative methylation analysis not only in malignancies.
Dermoscopy of small melanomas: just miniaturized dermoscopy?
Authors: S. Seidenari, C. Ferrari, S. Borsari, A. Fabiano, S. Bassoli, F. Giusti, G. Ponti, C. Magnoni
Journal: British Journal of Dermatology (2013)

Small malignant melanomas (MMs) are usually MMs in an initial growth phase, deserving attention by the clinician aiming at an early diagnosis.To identify clues for early diagnosis of small MMs, by comparing the dermoscopic features of MMs < 4 mm (micromelanomas) with those of larger MMs.Our database consists of dermoscopic images of 482 MMs, which have been retrieved and measured digitally. The ABCD (asymmetry, border, colour, dimension) and 7-point criteria were evaluated for the whole database by three expert dermoscopists, whereas the main dermoscopic pattern was assessed only for micromelanomas. The dermoscopic aspects were correlated to clinical and histological features.Most 7-point and ABCD scores, and criteria referring to micromelanomas, differed from those of the MM database as a whole. Lesion asymmetry, number of colours, blue-whitish veil, atypical vessels, irregular globules/dots and regression increased according to MM diameter. An inverse trend was observed for atypical network and irregular pigmentation, which were more frequently observed in micromelanomas than in larger ones. Among the 22 micromelanomas, 12 lesions were in situ, whereas the other 10 were 0·2-2 mm thick. The clinical and dermoscopic characteristics of the two groups were similar.Micromelanomas are not a rarity. However, the clinician should be aware of the fact that the majority of them lack most of the dermoscopic features presented by larger lesions.
Reassortment between Influenza B Lineages and the Emergence of a Coadapted PB1–PB2–HA Gene Complex
Authors: Gytis Dudas, Trevor Bedford, Samantha Lycett, Andrew Rambaut
Journal: Molecular Biology and Evolution (2014)

Influenza B viruses make a considerable contribution to morbidity attributed to seasonal influenza. Currently circulating influenza B isolates are known to belong to two antigenically distinct lineages referred to as B/Victoria and B/Yamagata. Frequent exchange of genomic segments of these two lineages has been noted in the past, but the observed patterns of reassortment have not been formalized in detail. We investigate interlineage reassortments by comparing phylogenetic trees across genomic segments. Our analyses indicate that of the eight segments of influenza B viruses only segments coding for polymerase basic 1 and 2 (PB1 and PB2) and hemagglutinin (HA) proteins have maintained separate Victoria and Yamagata lineages and that currently circulating strains possess PB1, PB2, and HA segments derived entirely from one or the other lineage; other segments have repeatedly reassorted between lineages thereby reducing genetic diversity. We argue that this difference between segments is due to selection against reassortant viruses with mixed-lineage PB1, PB2, and HA segments. Given sufficient time and continued recruitment to the reassortment-isolated PB1-PB2-HA gene complex, we expect influenza B viruses to eventually undergo sympatric speciation.
High-affinity IgE receptor (FcepsilonRI)-bearing cells in bronchial biopsies from atopic and nonatopic asthma.
Authors: M Humbert, J A Grant, L Taborda-Barata, S R Durham, R Pfister, G Menz, J Barkans, S Ying, A B Kay
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Asthma is characterized by bronchial mucosal inflammation. Although allergen-induced activation of cells binding allergen-specific immunoglobulin E (IgE) through high-affinity receptors (Fc(epsilon)RI) is believed to play some role in asthma, inappropriate synthesis of total or allergen-specific IgE cannot be demonstrated in some ("intrinsic") patients despite the fact that the nature of the bronchial inflammation is similar to that in atopic ("extrinsic") asthmatics. We have studied the numbers and phenotype of Fc(epsilon)RI-bearing cells in bronchial biopsies from 12 atopic and 10 nonatopic asthmatic patients and compared our findings with 10 atopic and 12 nonatopic control subjects using single and double immunohistochemistry. Significantly increased numbers of Fc(epsilon)RI-bearing cells were identified in bronchial biopsies from atopic and nonatopic asthmatics and atopic control subjects when compared with normal controls (p = 0.001, 0.006, and 0.0006, respectively). In asthmatics and atopics the majority of Fc(epsilon)RI-bearing cells were identified as mast cells and macrophages; a much smaller percentage were eosinophils. We conclude that elevated numbers of high-affinity IgE receptor-bearing cells are a feature of bronchial biopsies of asthmatic subjects, irrespective of their atopic status.