Intravascular histiocytosis O'Grady, J T; Shahidullah, H; Doherty, V R ...
Histopathology,
March 1994, Letnik:
24, Številka:
3
Journal Article
Recenzirano
The majority of cases of intravascular lymphomatosis are B-cell lymphomas with only the occasional case being of T-cell type. We report a case of intravascular lymphomatosis in which the ...proliferating cells were of histiocytic type; the tumour has recurred following treatment.
ABSTRACT
Atherosclerotic arteries frequently become calcified, and these calcium deposits are associated with a high risk of adverse clinical events. Descriptive studies suggest calcification is an ...organized and regulated process with many similarities to osteogenesis, yet the mechanism and its relationship to atherosclerosis remain largely unknown. In bone development and homeostasis, mineral deposition by osteoblasts and mineral resorption by osteoclasts are delicately balanced such that there is no overall gain or loss in bone mass. We hypothesize that there exists in arteries a mechanism that similarly balances mineral deposition with resorption. We propose that the cellular mediators of arterial mineral resorption are osteoclast‐like cells (OLCs) derived from hematopoietic precursors of the mononuclear phagocytic lineage. In arterial microenvironments, mononuclear precursors are induced to differentiate toward OLCs by macrophage‐colony stimulating factor and receptor activator of NF‐κB ligand, both of which are necessary and sufficient for osteoclastogenesis and mineral resorption in bone. OLCs may participate in normal mineral homeostasis within the arterial wall or, alternatively, may be recruited to specific sites within developing plaque. Net calcium deposition occurs as a result of focal perturbation of the balance between the activity of osteoblast‐like cells and OLCs. Our proposed mechanism thus views arterial mineral deposition not so much as an active pathological process, but as a localized failure of protective mechanisms that actively oppose mineral deposition within the disordered metabolic milieu of developing atherosclerotic plaque.—Doherty, T. M., Uzui, H., Fitzpatrick, L. A., Tripathi, P. V., Dunstan, C. R., Asotra, K., Rajavashisth, T. B. Rationale for the role of osteoclast‐like cells in arterial calcification. FASEB J. 16, 577–582 (2002)
A wastewater-treatment facility at Ford (Dearborn, Michigan) was recently upgraded from chemical de-emulsification to ultrafiltration (UF) followed by a membrane-biological reactor (MBR). This paper ...describes the design, startup, and initial operational performance of the facility. Primary findings are as follows: (1) the MBR proved resilient; (2) the MBR removed approximately 90% of chemical-oxygen demand (COD) after primary UF; (3) the removal of total Kjeldahl nitrogen by MBR appeared to be more sensitive to operating conditions than COD removal; (4) nitrification and denitrification were established in one month; (5) the MBR removed oil and grease and phenolics to below detection levels consistently, in contrast to widely fluctuating concentrations in the past; (6) permeate fluxes of the primary and MBR UF were adversely affected by inadvertent use of a silicone-based defoamer; and (7) zinc concentrations in the effluent increased, which might have been a result of ethylenediamine-tetraacetic acid used in membrane washing solutions and/or might have been within typical concentration ranges.
The
BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within ...a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1β and BS69, and localizes to sites of repair following DNA damage.
EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the
EMSY gene is amplified almost exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer (17%). In addition,
EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic
EMSY amplification and familial
BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.
Abstract
Background
Aberrations in various immune cell subsets have been identified in Crohn’s disease. However, most studies focus on a single type of immune cell in isolation, limiting our ...understanding of how cellular and humoural immune systems interact. In addition, heterogeneity of immune-phenotypes may explain variation in treatment response. We examined differences in immune-cell subsets in patients with Crohn’s disease commencing anti-TNF treatment.
Methods
Patients with Crohn’s disease commencing infliximab or adalimumab were recruited prospectively in the outpatient setting. Age-matched healthy controls were recruited contemporaneously with each patient. Demographic and clinical data including disease phenotype, CRP, calprotectin, and HBI were recorded. Blood samples were obtained from patients and matched controls at week 0, 2, and 14 (approx.) of treatment. Patients were deemed responders or non-responders at week 14 based on a composite of clinical scores, biomarkers, and need to escalate treatment. Flow cytometry using four panels comprising a total of 34 antibodies was used to analyse approximately 30 different cell types including B cells, T cells, and antigen-presenting cells (monocytes and dendritic cells). PRISM software was used for statistical analysis.
Results
Baseline comparison of 19 CD patients (Table 1) and controls shows multiple differences. Patients have a significantly lower frequency of MAIT (CD3+CD161++Vα7.2+) cells and non-classical monocytes (HLA-DR+CD14−CD16+). Patients also show a higher frequency of naïve (CD19+IgD+27−) B cells, and lower frequency of class-switched memory (CD19+IgD−CD27+) B cells (p < 0.05). 13 patients have reached the week 14 timepoint, enabling determination of treatment response. 8/13 (62%) patients are deemed responders. Baseline MAIT cell frequencies are strikingly lower in responders vs. non-responders (p < 0.05). Treatment with anti-TNF does not alter frequencies of MAIT cells, non-classical monocytes, naïve B cells, or class-switched memory B cells over a 14-week treatment period.
Table 1.
Patient Demographics.
Gender; n (%) male
13 (68%)
Age; mean (range)
35 years (19–66 years)
Previous resection; n (%)
6 (32%)
Infliximab; n (%), adalimumab; n (%)
IFX; 2 (11%), ADA; 17 (89%)
Immunomodulator; n (%)
7 (37%)
Steroids at anti-TNF induction
1 (5%)
Conclusions
Many immune cell subsets are perturbed in Crohn’s disease. However, only MAIT cell frequency was associated with response to anti-TNF. A low MAIT cell count in peripheral blood may signify TNF-predominant inflammatory response. This novel association between immune-phenotype and treatment response may aid patient-tailored treatment in the future.
The use of data from smartphones and wearable devices has huge potential for population health research given high device ownership, the range of novel health-relevant data types available from ...consumer devices, and the frequency and duration over which data are, or could be, collected. Yet the uptake and success of large-scale mobile health research in the last decade has not matched the hyped opportunity. We make the argument that digital person-generated health data is required and necessary to answer many top priority research questions through illustrative examples taken from the James Lind Alliance Priority Setting Partnership. We then summarise the findings from two UK initiatives that considered the challenges and possible solutions for what needs to be done, and in what way, to realise the future opportunities of digital person-generated health data for clinically important population health research. Examples of important areas to be addressed to advance the field include digital inequality and addressing possible selection bias, easy access for researchers to the appropriate data collection tools including how best to harmonise data items, analysis methodology for time series data, methods for patient and public involvement and engagement to optimise recruitment, retention and public trust, and providing greater control of their data to research participants. There is also a major opportunity through the linkage of digital persongenerated health data to routinely-collected data to support novel population health research, bringing together clinician-reported and patient-reported measures. We recognise that well conducted studies need a wide range of diverse challenges to be skilfully addressed in unison: for example, epidemiology, data science and biostatistics, psychometrics, behavioural and social science, software engineering, user interface design, information governance, data management and patient and public involvement and engagement. Consequently, progress would be accelerated by the establishment of a new interdisciplinary community where all relevant and necessary skills are brought together to allow excellence throughout the lifecycle of a research study. This will require a partnership of diverse people, of methods and of technology. Get this right and the synergy has the potential to transform many millions of people’s lives for the better.
Between 2006 and 2010, recurring morbidity mid mortality of the endemic Lake Oku clawed frog Xenopus longipes was observed at its only known locality, Lake Oku, Cameroon. During repeated visits in ...200fi, 200K, 2009 and 2010, we found large numbers of dead frogs around the lake shore, as well as a higher than expected prevalence of diseased frogs. No significant relationships between disease occurrence and environmental parameters were found, with the exception of a significant but unexplained association between phosphate concentration and disease incidence. Tissue samples from X. longipes collected during 3 field seasons were negative for the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) using a Bd-specific real-time PCJR test, although other species of sympatric amphibians were positive for this pathogen. Only 1 of 48 tissue samples from diseased frogs was positive for ranavirus infection using a ranavirus-specific FCR, suggesting that this pathogen is not necessarily the cause of this disease. No evidence of pathogens was found in tissues examined histologically from 10 X. longipes which had been collected and fixed when freshly dead. The cause(s) of the morbidities and mortalities remain(s) unknown, as does their consequence to the population of this Critically Endangered species. Identifying the causative factor(s) of the X. longipes mortality and its impact on the population is crucial for planning conservation actions.
Walker responds to Doherty, Kouneski and Erickson's "Responsible Fathering," stating that the proposed model excludes key features of fatherhood and of motherhood. Researchers who attempt to ...operationalize it or practitioners who attempt to develop programs from it are destined to be misguided.
Summary
The immunological function of the Langerhans cell (LC) network in neonatal skin was examined by defining the development of cutaneous immunity relative to the structure, phenotype and ...function of the epidermal LC network in neonatal, juvenile and adult mice. Analysis of epidermal sheets showed the presence of major histocompatibility complex (MHC) II+, multilectin receptor DEC‐205– cells within the epidermis of 3‐day‐old mice; both cell density and DEC‐205 expression increased until day 14. When visualized with antibodies directed at MHC II, the network was poorly formed in 3‐ and 7‐day‐old mice, as there was a lower cell density and poor MHC II expression on dendritic processes, compared to mice at day14. Application of a fluorescent antigen to 3‐day‐old mice revealed that the LC were inefficient in transporting antigen to the draining lymph node. There was an improvement at day 7 and by day 14 comparable numbers of antigen carrying cells were detected in the lymph nodes of 6‐week‐old mice. The reduced antigen carriage in 3‐ and 7‐day‐old mice correlated with a poor contact sensitivity response. This was not simply due to failure to present antigen, but development of immunosuppression, as transfer of T cells from adult mice that were previously treated with antigen when they were 3 days old, to adult recipients resulted in antigen specific immunosuppression. Analysis of CD80 and CD86 expression showed that LC from day 3 skin expressed CD80, but not CD86 and application of antigen through this skin was inefficient in upregulating CD86. These findings indicate that when the neonatal LC network is poorly developed it is functionally immature and antigen applied through this ‘functionally immature network’ results in antigen specific immunosuppression.
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