63 research outputs found
Re-evaluation of histological diagnoses of malignant mesothelioma by immunohistochemistry
<p>Abstract</p> <p>Background</p> <p>In order to provide reliable tissue material for malignant mesothelioma (MM) studies, we re-evaluated biopsies and autopsy material from 61 patients with a diagnosis of MM from the period of 1980-2002.</p> <p>Methods</p> <p>Basic positive (Calretinin, EMA, Podoplanin, Mesothelin) and negative (CEA, Ber-Ep4) immunohistochemical (IHC) marker reactions were determined. If needed, more markers were used. Histological diagnoses were made by three pathologists. Survival data were calculated.</p> <p>Results</p> <p>49 cases (80%) were considered being MM by a high degree of likelihood, five more cases possible MM. Of the remaining seven cases, three were diagnosed as adenocarcinoma, three as pleomorphic lung carcinoma, in one peritoneal case a clear entity diagnosis could not be given. One of the possible MM cases and two of the lung carcinoma cases had this already as primary diagnoses, but were registered as MM.</p> <p>With a sensitivity of 100%, Calretinin and CEA were the most reliable single markers. The amount of MM cells with positive immunoreactivity (IR) for Podoplanin and Mesothelin showed most reliable inverse relation to the degree of atypia.</p> <p>In the confirmed MM cases, there had been applied either no IHC or between one and 18 markers.</p> <p>The cases not confirmed by us had either lacked IHC (n = 1), non-specific markers were used (n = 4), IR was different (n = 1), or specific markers had not shown positive IR in the right part of the tumour cells (n = 3).</p> <p>46 of the 49 confirmed and three of the not confirmed cases had been diagnosed by us as most likely MM before IHC was carried out.</p> <p>Conclusions</p> <p>In order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment.</p
Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients
<p>Abstract</p> <p>Background</p> <p>Calretinin is one of the well-established immunohistochemical markers in the diagnostics of malignant mesothelioma (MM). Its utility as a diagnostic tool in human blood, however, is scarcely investigated. The aim of this study was to develop an enzyme-linked immunosorbent assay (ELISA) for human calretinin in blood and to assess its usefulness as a potential minimally invasive diagnostic marker for MM.</p> <p>Methods</p> <p>Initially, attempts were made to establish an assay using commercially available antibodies and to optimize it by including a biotin-streptavidin complex into the assay protocol. Subsequently, a novel ELISA based on polyclonal antibodies raised in rabbit immunized with human recombinant calretinin was developed. The assay performance in human serum and plasma (EDTA/heparin) and the influence of calcium concentrations on antibody recognition were studied. Stability of spiked-in calretinin in EDTA plasma under different storage conditions was also examined. In preliminary studies serum and plasma samples from 97 healthy volunteers, 35 asbestos-exposed workers, and 42 MM patients were analyzed.</p> <p>Results</p> <p>The mean detection range of the new ELISA was 0.12 to 8.97 ng/ml calretinin. The assay demonstrated markedly lower background and significantly higher sensitivity compared to the initially contrived assay that used commercial antibodies. Recovery rate experiments confirmed dependence of calretinin antibody recognition on calcium concentration. Calcium adjustment is necessary for calretinin measurement in EDTA plasma. Spiked-in calretinin revealed high stability in EDTA plasma when stored at room temperature, 4°C, or after repeated freeze/thaw cycles. Median calretinin values in healthy volunteers, asbestos workers, and MM patients were 0.20, 0.33, and 0.84 ng/ml, respectively (p < 0.0001 for healthy vs. MM, p = 0.0036 for healthy vs. asbestos-exposed, p < 0.0001 for asbestos-exposed vs. MM). Median values in patients with epithelioid and biphasic MM were similar. No influence of age, gender, smoking status, or type of medium (plasma/serum) on calretinin values was found.</p> <p>Conclusions</p> <p>The novel assay is highly sensitive and applicable to human serum and plasma. Calretinin appears to be a promising marker for the blood-based detection of MM and might complement other markers. However, further studies are required to prove its usefulness in the diagnosis of MM patients.</p
The response of plant community diversity to alien invasion: evidence from a sand dune time series
This study examines the process of invasion of coastal dunes in north-eastern Italy along a 60-year time series considering alien attributes (origin, residence time, invasive status, and growth form strategy) and habitat properties (species richness, diversity and evenness, proportion of aliens, and proportion of focal species). Vegetation changes through time were investigated in four sandy coastal habitats, using a fine-scale
diachronic approach that compared vegetation data collected by use of the same procedure, in four time periods, from the 1950s to 2011. Our analysis revealed an overall significant decline of species richness over the last six decades. Further, both the average number of species per plot and the mean focal species proportion were proved to be negatively
affected by the increasing proportion of alien species at plot level. The severity of the impact, however, was found to be determined by a combination of species attributes, habitat properties, and human disturbance suggesting that alien species should be referred to as ‘‘passengers’’ and not as ‘‘drivers’’ of ecosystem change. Passenger alien species are those which take advantage of disturbances or other changes to which they are adapted but that lead to a decline in native biodiversity. Their spread is facilitated by widespread anthropogenic environmental alterations, which create new, suitable habitats, and ensure
human-assisted dispersal, reducing the distinctiveness of plant communities and inducing a process of biotic homogenization
Deliberate self-harm and attachment: mediating and moderating roles of depression, anxiety, social support and interpersonal problems among Pakistani school going adolescents
Introduction: In Pakistan there is dearth of research on deliberate self-harm (DSH) and
its predictors among adolescents. While the lack of research in Pakistan can be partly
attributed to the sacrilegious status, criminalization and stigmatization attached to DSH, it
is also an attribute of paucity of Urdu versions of the standardized psychological
instruments. Previous research in developed countries has indicated that attachment theory
can be used as a useful framework to understand the development of austere
psychopathologies like DSH, as well as for studying pathways of interaction of
interpersonal and intrapersonal factors of psychopathologies. In this study, standardized
psychological instruments are translated into Urdu language as a first step. These
instruments are then used to study pathways of interaction of interpersonal and
intrapersonal factors of DSH, conceptualized within attachment framework.
Method: The study was conducted in two steps. In step 1, Youth Health Risk Behavior
Survey (YHRB), Inventory of Interpersonal Problems-32 (IIP-32) and Significant Others
Scale (SOS), were translated into Urdu language. Along with these scales, Urdu translated
versions of Hospital Anxiety and Depression Scale (HADS), Adolescent Relationship
Scales Questionnaire (ARSQ), Life Events scale (LES) from CASE questionnaire and
Family Affluence Scale-II (FAS-II) were reviewed for accuracy of translation through
expert judgement and psychometric evaluation. Secondly, a cross sectional survey was
conducted with 1290 adolescents (10 - 19 years age) using the translated Urdu versions of
the instruments and demographic pro forma. Structural equation modelling was used to
study the pathways of associations between predictors of DSH.
Results: The extensive process of translation resulted in establishment of semantic,
content, technical and construct equivalence of the translated instruments with the original
English versions. Multiple imputation was performed to account for missing values in
SPSS 20. Important structural adaptations were made in the scales based on factor analyses
conducted in M plus. After modifications, all scales showed satisfactory CFI (≥ 0.90) and
RMSEA (≤ 0.06). Results of the survey indicated that the prevalence of DSH (with, without
and ambivalent suicidal intentions) was 7%. Two SEM models were constructed involving
both mediation and moderation pathways. Results of Model 1 showed association of
attachment with DSH was double mediated by social support, depression and anxiety.
Model 2 also confirmed association of attachment with DSH with double mediation
through relationship style problems, depression and anxiety. In order to understand the
contextual picture of the concepts studied in this research both SEM models were also
constructed by controlling for demographic factors. This resulted in confirming age,
gender and family affluence as significant contributors but with very small effects.
Discussion and conclusion: In the present study translation of the instruments helped in
building a reservoir for future research. The results of translation and validation of
instruments indicated that cultural differences, language needs and age must be accounted
for while using standardized psychological instruments. Taking into consideration specific
cultural and demographic background of Pakistan, this study also confirms the key role of
attachment in influencing interaction of predictors of DSH. It is suggested that
intrapersonal and interpersonal factors are influential points of intervention for designing
clinical, school and community based awareness and prevention programs for DSH. The
thesis also discusses the implications for policy guidelines along with recommendations
for future research and other applications of the study
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