The gene for human lymphocyte homing receptor is located on chromosome 11

The mouse monoclonal antibody Hermes-3 recognizes the human lymphocyte homing receptor. A panel of mouse-human T lymphocyte hybrids, carrying all mouse chromosomes and a limited number of human chromosomes, was analyzed for expression of human homing receptor by indirect immunofluorescence and immunoprecipitation of radiolabeled cell lysates with Hermes-3 antibody. Karyotypic analysis of the tested clones showed that the expression of human homing receptor correlated to the presence of human chromosome 11 in all but one clone. However, concanavalin A induced a weak to moderate expression of the homing receptor in this clone, but not in a chromosome 11- clone. Another clone, heterogeneous for the expression of homing receptor, was separated into a Hermes-3+ and a Hermes-3- fraction with a fluorescence-activated cell sorter. Karyotypic analysis performed after sorting showed human chromosome 11 to segregate with the Hermes-3 antigen. To confirm these data we correlated the expression of two chromosome 11-coded antigens, Trop-4 and Leu-7, with the expression of the homing receptor. In our hybrid clones these three antigens were expressed concordantly. The gene coding for the human lymphocyte homing receptor recognized by Hermes-3 is thus assigned to chromosome 11.     

Organ-selective regulation of vascular adhesion protein-1 expression in man

Vascular adhesion protein-1 (VAP-1) is an endothelial molecule which mediates lymphocyte binding to endothelium in peripheral lymph nodes and at certain sites of inflammation. The expression of VAP-1 in vivo is strongly up-regulated in inflamed tissues, such as gut and skin. The purpose of this work was to examine the factors responsible for this induction of VAP-1. Since the expression of VAP-1 could not be induced in cultured endothelial cells with a large panel of mediators, we used an organ culture technique for the investigation of the regulation of VAP-1 expression in a more physiological micromilieu. Indeed, we found that the expression of endothelial VAP-1 could be up-regulated in human tonsillar tissue with interleukin (IL)-1, IL-4, tumor necrosis factor (TNF-α), interferon (IFN)-γ and lipopolysaccharide, whereas histamine, thrombin, dibutyryl cAMP, N-formyl-Met-Leu-Phe (fMLP) and phorbol 12-myristate 13-acetate (PMA) had no effect. The induced VAP-1 protein was similar in molecular weight to the non-induced VAP-1, suggesting that VAP-1 synthesized de novo carries appropriate carbohydrate moieties. In contrast to tonsil organ culture, similar inductions performed with human appendix showed no up-regulation of VAP-1 expression, indicating that the regulation of VAP-1 expression exhibits organ-selective characteristics. Furthermore, in these tissues the smooth muscle cells, which constitutively express VAP-1, could not be stimulated to alter their level of expression of this molecule. In conclusion, the expression of VAP-1 can be markedly up-regulated with several mediators in tonsil but not in appendix organ culture, whereas cultured endothelial cells cannot be induced to express VAP-1. These results indicate that the expression of VAP-1 is regulated in a tissue- and cell type-selective manner, and a correct micromilieu is required for the up-regulation to occur.     

Clinical supervision as an interaction between the clinical educator and the student

The interaction between clinical educators and students is regarded as the strongest element in developing expertise and in forming students' professional identity in clinical education. Although clinical education has been studied in physiotherapy, the natural interaction between clinical educators and students has remained unanalyzed. The aim of this study was to examine how supervised learning sessions during patient treatment were constructed. The focus was on the forms of interaction between clinical educators and students in natural contexts. By videotaping 12 natural patient treatment sessions, which simultaneously comprised part of the clinical education of physiotherapy students, and by using qualitative discourse analysis, three supervision discourses emerged from the data: "directing the interaction," "making limited room for the student," and "encouraging the student's participation." This study revealed that clinical educators have a dominant role in constructing supervised learning sessions during patient treatment. Depending on how the interaction is constructed, it is possible to support or prevent student participation in decision making as well as to promote or reject the rehearsal of critical thinking or self-directed learning among students. This study highlighted the importance of interactional skills in supervision practices. More research into constructing learning sessions in clinical education is needed.     

Exposure to refractory ceramic fibres in the metal industry

Refractory ceramic fibres (RCF) are used in thermal isolation in the metal industry where high temperatures are regularly employed. Asbestos materials were earlier commonly used for these purposes. In this work, two Finnish steel plants, three foundries and a repair shop were studied for the ceramic fibre exposure of their workers under normal production and during the replacement of oven insulation. Personal and stationary sampling was used together with a novel nasal lavage sampling for the evaluation of personal exposure. Fibres were counted with optical and electron microscopy and they were identified using an energy-dispersive X-ray analyser. Ceramic fibres were found in most production phases [range <0.01-0.29 fibres per cubic centimetre (f cm(-3))]. Considerably higher fibre counts were obtained during the maintenance work (range <0.01-14.2 f cm(-3)). Nasal sampling was found to correlate with the airborne fibre concentrations at the group level. The mean fibre concentrations varied from 34 to 6680 f ml(-1) of lavage liquid. Use of personal respiratory protectors diminished the exposure on the average as analysed in the lavage specimens, but the effect of respirator use did not appear clearly in the results. Because of the heat conditions, the workers used the respirators for a strict minimum period. A considerable exposure to RCF occurs in the studied plants. Its risk should be evaluated and managed more closely in view that the material is carcinogenic. Use of personal respiratory protectors should be encouraged. Their effective use could be verified by the nasal sampling for fibres after the work shift.     

Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by The Nordic Lymphoma Group

The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Patients aged 18–75 years were eligible. Thirty-nine patients aged 18–65 years and 27 patients aged 66–75 years were enrolled. The median age of the two age groups was 55 and 70 years, respectively. The overall response rate was 73.8% for the entire cohort: 69.9% in the younger and 80.8% in the elderly subgroup. With a median follow up of 22 months, the 2-year overall survival probability was 60.7% in patients aged 65 years or under and 55.6% in patients aged over 65 years (P=0.40). The estimated progression-free survival at two years was 33.1% (95%CI: 19.1%–47.9%) in patients aged under 65 years and 44.4% (95%CI: 25.6%–61.8%) in the elderly subgroup (P=0.74). Median duration of response was ten months in the younger subgroup, and not reached in the elderly patient subgroup (P=0.33). Four patients aged 64–75 years (6%) died from treatment-related complications. Survival in the two age groups was similar despite a de-escalation of induction treatment in patients aged over 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern, especially in the elderly patients, we conclude from these data that de-escalation of induction therapy in elderly primary central nervous system lymphoma patients followed by maintenance treatment seems to be a promising treatment strategy. (clinicaltrials.gov identifier:01458730)     

Is work engagement related to work ability beyond working conditions and lifestyle factors?

Purpose

To examine the associations of age, lifestyle and work-related factors, and particularly work engagement with the work ability index (WAI) and its sub-dimensions.

Methods

Step-wise regression analysis with a sample of Finnish firefighters (n?=?403) was used. The outcome variables were the WAI and its six sub-dimensions. The independent variables consisted of age, lifestyle variables (alcohol consumption, BMI, smoking, physical exercise, and sleep problems), working conditions (job demands, physical workload, supervisory relations, and task resources), and work engagement. The outcome variables and all the variables related to lifestyle, working conditions, and work engagement were measured in 2009. Work ability at baseline 10?years earlier was adjusted for in the models.

Results

Work engagement, age, physical exercise, sleep problems, and physical workload were associated with the WAI. All independent variables, except BMI and alcohol consumption, were associated with at least one sub-dimension of the WAI after controlling the baseline WAI. Lifestyle variables, working conditions, and work engagement were more strongly related to the subjective WAI sub-dimensions than to the two more objective WAI sub-dimensions.

Conclusions

Work engagement was significantly associated with work ability even after adjusting for various factors, indicating its importance in promoting work ability. Other key factors for good work ability were frequent exercise, good sleep, non-smoking, low job demands, low physical workload, and high task resources. More specifically, this study suggests that in maintaining work ability, it is valuable not only to promote lifestyle factors or working conditions, but also to enhance employees’ positive state of work engagement.     

Protection by nitecapone against sodium taurocholate-induced damage to cultured gastric cells

The goal of this study was to observe if nitecapone protected against taurocholate-induced damage in primary cultured rat gastric mucosal cells, as well as in a well-differentiated human gastric epithelial cell line (MKN 28). Prostaglandins were measured to analyze the protection mechanism. In primary rat gastric mucosal cell culture, nitecapone 125–250 M protected the cells significantly against damage induced by sodidum taurocholate, increasing cell viability by 31–38%. In the human gastric epithelial cell line, in which mitochondrial activity was measured as an indication of cell viability, nitecapone (62.5–250 M) protected the cells against sodium taurocholate-induced damage by 12–20%. Prostaglandin E₂, thromboxane B₂, and 6-keto-prostaglandin F₁ measurements in the primary cultured rat gastric mucosal cells showed that nitecapone (125 M and 250 M) significantly stimulated prostaglandin E₂ production (84.7% and 61.0%, respectively), and inhibited thromboxane B₂ formation (50% at 250 M), while the 6-keto-prostaglandin F₁ formation was unaffected. Nitecapone had no effect on prostaglandin E₂ production in the MKN 28 epithelial cell line. Indomethacin or aspirin, at concentrations that did not affect cell viability, antagonized the stimulative effect of nitecapone on prostaglandin E₂ formation in the primary cultured rat gastric mucosal cells. Although the prostaglandin E₂ synthesis was blocked, nitecapone still protected against cell damage induced by taurocholate. These results demonstrated the direct and efficacious protection of nitecapone on gastric cell level and suggest that the cytoprotection by nitecapone against taurocholate may not be mediated through the mechanism of stimulated synthesis of prostaglandin E₂.     

Prognostic impact of CD31-positive microvessel density in follicular lymphoma patients treated with immunochemotherapy

BackgroundTumour-infiltrating mast cells (MCs) can remodel tumour microenvironment and growth by suppressing immune responses and potentiating angiogenesis. Furthermore, accumulation of MCs in follicular lymphoma (FL) correlates with unfavourable prognosis after immunochemotherapy. Here we investigated whether tumour vascularity is associated with MC content and outcome in FL patients treated with immunochemotherapy.Patients and methodsMicrovessel density (MVD) and MC content were determined immunohistochemically from pretreatment samples of 95 FL patients using CD31, CD34 and mast cell tryptase antibodies. Gene expression data from a separate set of 24 FL patients were analysed for comparison. All patients were treated with the combination of rituximab (R) and cyclophoshamide-doxorubicin–vincristine–prednisone (CHOP) chemotherapy.ResultsIncreased CD31+ MVD correlated positively with the number of tumour infiltrating MCs and CD34+ vessels, and negatively with the outcome. Overall survival and progression-free survival were significantly better among patients with low CD31+ MVDs. In multivariate analyses, CD31+ MVD had prognostic value independently of Follicular Lymphoma Prognostic Index but not of MC content. Consistent with the immunohistochemical data, high CD31/PECAM1 mRNA levels were associated with adverse outcome. Conversely, a positive prognostic impact of VEGF mRNA expression on the outcome was found.ConclusionVascularity is associated with MC content and outcome in R-CHOP-treated FL patients.