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Summary: Psoriasis is a common, inflammatory immune‐mediated skin disease mainly presenting with plaques whose pathogenesis is based on the central role of the interleukin (IL)‐23/IL‐17 axis. However, the mechanisms acting in papular lesions of early‐phase psoriasis are not fully understood. The aim of this study was to assess the involvement of autoinflammation, a state of sterile inflammation mainly driven by IL‐1 over‐production that has been recently hypothesized to act in the early phase of disease. Lesional skin of 10 patients with recent onset, untreated psoriasis has been investigated for expression of IL‐1β, IL‐17, IL‐23 and other cytokines involved in the disease in comparison with normal skin of 10 healthy controls using a protein array method. Immunohistochemical phenotyping of inflammatory infiltrate and co‐localization experiments with immunofluorescence confocal microscopy were conducted. IL‐1β was significantly more expressed in psoriasis than in normal skin (P < 0·0001). The chemokine IL‐8 was also over‐expressed in psoriasis (P = 0·03) while IL‐12, IL‐17, IL‐23, tumour necrosis factor‐α and interferon‐γ were only slightly more expressed in psoriasis than in normal skin, without reaching statistical significance. The inflammatory infiltrate consisted mainly of neutrophils with a relevant number of macrophages and dendritic cells and only scattered, predominantly T helper 1 lymphocytes. IL‐1β co‐localized mainly with CD66b, a neutrophil marker, suggesting that neutrophils were the major source of this cytokine. IL‐1β over‐expression in combination with low expression of cytokines that are predominant in late‐phase plaque psoriasis may support the role of autoinflammation in early‐phase disease, possibly paving the way to randomized trials with IL‐1 antagonists. [ABSTRACT FROM AUTHOR]

Background The British system ( Thy1-5), the Bethesda system for reporting thyroid cytopathology ( BSRTC) and the Italian Society of Anatomic Pathology and Cytology ( SIAPEC) classification represent the most important international classifications for thyroid cytopathology. Irrespective of the system used, the 'indeterminate' categories are still debated among cytopathologists, particularly with regard to diagnostic criteria, clinical impact of subclassification and role of molecular techniques. Aim We aimed to find answers to the following questions: Are there shared criteria in cytological preparations that allow the division of indeterminate follicular lesions into subcategories? What is the true clinical impact of this possible subclassification? Methods Among 1150 consecutive thyroid fine needle aspiration ( FNA) specimens, 80 patients had nodules with a final cytological report of Tir3 ( SIAPEC)/ Thy3. These 80 cases were re-evaluated and subclassified according to morphological criteria into three groups: pure follicular proliferations, Hürthle cell follicular lesions and atypical proliferations. Results Sixteen (20%) cases were categorized as pure follicular proliferations, 40 (50%) as Hürthle cell follicular lesions and 24 (30%) as atypical proliferations. Surgery was performed in 57 cases (71%). Cyto-histological correlation showed that follicular adenoma was the most frequent final diagnosis in the cases treated by surgery (24/57, 42%). The overall malignancy rate in the Tir3 category was 28% (16/57). Atypical proliferations were more often malignant than either of the follicular groups (53% versus 19%, P = 0.019). Conclusions A five-tiered classification, subdividing the 'indeterminate for malignancy' class into 'follicular proliferations' and 'atypical lesions' could be adopted. As a result of their higher risk of malignancy, surgical management of the atypical lesions would be justified. In future, the introduction of a genetic panel might contribute to their stratification, to the determination of a more accurate risk of malignancy of the atypical lesions and to the verification of follicular proliferations that are benign. [ABSTRACT FROM AUTHOR]

Sclerosing mesenteritis is a rare, idiopatic, usually benign, inflammatory process of the mesenteric adipose tissue. The most common site of involvement is the small bowel mesentery. We present a case of sclerosing mesenteritis of the rectosigmoid colon as a cause of severe abdominal pain, abdominal obstruction, and ischemic colic mucosal lesions. Contrast enema, colonoscopy, angiography, and CT were the imaging modalities used. A 20 cm diameter, fibrotic mass causing extensive compression of rectosigmoid colon was found at laparotomy. Histological examination showed extended fibrosis, inflammatory cells infiltration, lipophages, and granulomas within the mesenteric adipose tissue associated with erosive colitis. Clinical presentation and treatment are discussed. [ABSTRACT FROM AUTHOR]

This paper is an introduction to the following articles in the scope of quantum mechanics for space study initiated by ESA and lead by ONERA. The context of quantum mechanics for space is summarised, and the fields under development are briefly introduced. Technological applications of quantum mechanics in space are explored and some tests of quantum mechanics are outlined. We also give a brief presentation of the opto-electronic section of the European Space Agency, and the technology development activities it carries out, with particular emphasis on those activities related to the topics of interest of the quantum mechanics in space workshop. As an example, a summary of two ESA studies on gravity gradiometry and their relevance to the field of atomic interferometry is given. In view of the scientific requirements, derived for both Earth observation and planetology for future space missions, atom interferometry shows promise and may provide an advantage over currently available accelerometer and inertial sensor systems. [ABSTRACT FROM AUTHOR]

SHAHIRA (Submm Heterodyne Array for High-speed Radio Astronomy) is a project supported by the European Space Agency (ESA) and is designed to fly on the SOFIA observatory. A quasi-optic design has been chosen for 2.5/2.7 THz and 4.7 THz, for hydroxyde radical OH, deuterated hydrogen HD and neutral atomic oxygen OI lines observations. Hot electron bolometers (HEBs) have been processed on 1 μm thick stress-less membranes. In this paper we analyse the intermediate frequency (IF) gain bandwidth from the theoretical point of view, and compare it to measurements. [ABSTRACT FROM AUTHOR]

In the present study, the primary tumor angiogenesis characteristics of 81 stage IV previously untreated breast cancers with synchronous metastasis to different distant sites (10 patients with soft tissue metastases, 31 with bone metastases, and 40 with visceral metastases) were analyzed. The primary intratumor microvessel density was assessed by immunohistochemical assay on paraffin-embedded primary tumor samples, using a monoclonal anti-CD34 antibody. The mean primary intratumor microvessel density (at 400× fields) was 78±39 (SD) microvessels per field. The microvessel density was not significantly related to the main clinical/pathological features of the tumor (age, cytohistological grade, DNA ploidy, diameter, and receptor status). The percentage of tumor cases with high primary intratumor microvessel density (cut-off median value of the series 73±39 microvessels/field) did not significantly differ in patients with bone, soft tissue, or visceral metastatic disease. Aanalysis of clinical outcome showed a significantly shorter time to progression and overall survival for patients with visceral metastases ( P<0.001 and P<0.0002 by log-rank, respectively). Presence of visceral metastases was confirmed to be the only independent prognostic factor related to a worse TTP (hazard risk 2.15, 95% confidence interval 1.14–4.03, P<0.02) and overall survival (hazard risk 1.81, 95% confidence interval 0.98–3.35, P<0.06) by multivariate analysis. In conclusion, the assessment of neoangiogenesis of primary breast cancer by CD34 expression does not provide information predictive of different distant sites of metastasis. [ABSTRACT FROM AUTHOR]

Analyzes direct current and submillimeter pumped current-voltage characteristics of a hybrid superconductor-insulator-superconductor terahertz mixer. Hot electron effect due to the presence of the Nb/NbTiN interface; Device design and fabrication.

The clinical relevance of bax and bcl-2 protein expression has been investigated in 84 patients with recurrent or metastatic colorectal cancer submitted to a chemotherapy regimen including methotrexate and fluorouracil/leucovorin. Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%, respectively, of the tumours. No association was found between bax and bcl-2 or between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were unrelated to patient and tumour characteristics known to affect the clinical outcome of colorectal cancer patients. In general, the apoptosis-related markers did not appear indicative of short- and long-term clinical response nor of prognosis. Bcl-2-negative lesions were more frequent among patients who reached an objective clinical response, which is in agreement with previously reported data regarding other tumour types. When the interrelationship between p53 and bax expression was examined, a better response rate (40%) was found for patients whose tumours did not express p53 and bax, and a better prognosis (2-year probability of overall survival 75%) for patients with p53-positive and bax-negative tumours. In the present series of patients with advanced colorectal cancer submitted to systemic chemotherapy we did not find a clear association between expression of apoptosis-related markers and clinical outcome, even in the subset of patients in which the apoptotic index as determined by the TUNEL approach was investigated. [ABSTRACT FROM AUTHOR]

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated-5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53- cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively; P < 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P < 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34-1.01; two-sided P < 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85-1.26; two-sided P < 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy. (c) 2000 Cancer Research Campaign. [ABSTRACT FROM AUTHOR]

To identify prognostic subgroups among non-functioning (nonsyndromic) pancreatic endocrine tumours, a series of 61 tumours were analysed systematically for macroscopic, histopathological and immunohistochemical variables potentially predictive of malignancy. High-grade nuclear atypia, elevated mitotic rate and multifocal necrosis allowed us to separate 5 poorly differentiated carcinomas from 56 well differentiated tumours. Among the latter, 29 well-differentiated carcinomas showing gross local invasion or metastases were identified. Vascular or perineural microinvasion, Ki67 proliferative index > 2%, mitotic rate > or = 2, size > or = 4 cm, capsular penetration, nuclear atypia, lack of progesterone receptors and presence of calcitonin were among the variables correlated with malignancy. The first two were the most sensitive and specific. Their presence or absence was used in the 27 tumours lacking evidence of malignancy at the time of surgery to separate 11 cases with increased risk of malignancy (in 2 of which metastases developed during follow-up) from 16 cases with limited risk. The resulting four prognostic groups of non-functioning pancreatic endocrine tumours (limited- and increased-risk tumours, well-differentiated carcinomas and poorly differentiated carcinomas) showed distinct survival curves, which were significantly affected by vascular microinvasion, Ki67 proliferative index and metastases. [ABSTRACT FROM AUTHOR]

To identify prognostic subgroups among nonfunctioning (nonsyndromic) pancreatic endocrine tumours, a series of 61 tumours were analysed systematically for macroscopic, histopathological and immunohistochemical variables potentially predictive of malignancy. High-grade nuclear atypia, elevated mitotic rate and multifocal necrosis allowed us to separate 5 poorly differentiated carcinomas from 56 well differentiated tumours. Among the latter, 29 well-differentiated carcinomas showing gross local invasion or metastases were identified. Vascular or perineural microinvasion, Ki67 proliferative index >2%, mitotic rate ≥2, size ≥4 cm, capsular penetration, nuclear atypia, lack of progesterone receptors and presence of calcitonin were among the variables correlated with malignancy. The first two were the most sensitive and specific. Their presence or absence was used in the 27 tumours lacking evidence of malignancy at the time of surgery to separate 11 cases with increased risk of malignancy (in 2 of which metastases developed during follow-up) from 16 cases with limited risk. The resulting four prognostic groups of nonfunctioning pancreatic endocrine tumours (limited- and increased-risk tumours, well-differentiated carcinomas and poorly differentiated carcinomas) showed distinct survival curves, which were significantly affected by vascular microinvasion, Ki67 proliferative index and metastases. [ABSTRACT FROM AUTHOR]

Study objective – The aim was to investigate the effects of regional myocardial ischaemia, calcium, and verapamil on (a) the hysteresis and (b) slope and length axis intercept of the left ventricular end systolic pressure-length relationship.Design – Segment length in myocardium supplied by the left anterior descending coronary artery was measured in anaesthetised dogs using sonomic-rometry. Three levels of regional myocardial ischaemia were produced by stenosis and occlusion of the left anterior descending artery (ischaemia 1, ischaemia 2, and occlusion). A snare placed around the descending thoracic aorta was used to obtain temporary aortic occlusions.Subjects – Seven open chested mongrel dogs were used, weight 17 kg (range 16–20).Measurements and main results – After abrupt release of temporary aortic occlusions, end systolic lengths were greater than before the occlusion in the normal myocardium. This hysteresis was abolished by regional myocardial ischaemia. However, hysteresis was insensitive to calcium and verapamil. The length axis intercept of the end systolic pressure-length relationship was increased during ischaemia 2, during coronary occlusion, and after administration of verapamil; its slope was increased after coronary occlusion.Conclusions – (1) Viscoelastic properties of the myocardium make a major contribution to hysteresis of the end systolic pressure-length relationship; and (2) the length axis intercept of this relationship is not constant and its slope does not appear to be a sensitive indicator of regional myocardial contractility during regional ischaemia. [ABSTRACT FROM PUBLISHER]

We describe the gap voltage depression and current-voltage (I-V) characteristics in pumped niobium superconductor-insulator-superconductor junction with niobium titanium nitride tuning stripline by introducing an electron heating power contribution resulting from the photon-assisted tunneling process. Theoretical fits using the extended Tien-Gordon theory are obtained that reproduce the most salient features of the pumped I-V characteristics. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on the use of fine needle aspiration (FNA) cytology for detecting signet-ring cell (SRC) differentiation in a patient with primary thyroid cancer.

A letter to the editor is presented regarding the cytology and histological findings on thyroid florid papillary hyperplasia.

We analyze the current-voltage characteristics of a Nb superconductor-insulator-superconductor mixer with NbTiN leads to identify the heating processes in this device. We argue that the electron-electron interaction is much faster than the electron-phonon interaction, and show that the heat flow to the bath temperature is limited by the electron-phonon interaction time in the junction. A solution is suggested to considerably reduce the heating. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The Tonocap was used successfully to detect gut mucosal hypoperfusion in a canine model of hemorrhage. With re-injection of sampled air there was no suggestion of CO2 depletion during hypoperfusion. [ABSTRACT FROM AUTHOR]

We found a good mean correlation between intestinal luminal PCO2 measured with saline tonometry and the Tonocap. However, the difference between some of the paired measurements may be great enough to be of clinical significance (ie. greater than 8 mmHg). Results of an in-vitro validation study suggest that most of this variation can be attributed to the previously reported imprecision in the measurement of CO2 in saline samples using commercial blood gas analyzers (2). [ABSTRACT FROM AUTHOR]