Immunohistochemical expression of matrix metalloproteinases in the granulomatous rosacea compared with the non‐granulomatous rosacea

Background There is a granulomatous variant which is recognized in the rosacea spectrum. However, the pathogenesis of granuloma formation in rosacea has not been clearly demonstrated. Matrix metalloproteinases (MMPs) are required for recruitment of inflammatory cells and for tissue remodelling, making way for the development of well‐organized granuloma. Objective The aim of this study was to investigate the expression of transforming growth factor (TGF)‐β, TGF‐β type II receptor (TβRII), Tumour necrosis factor (TNF)‐α, MMP‐1, 2 and 9 in the granulomatous rosacea (GR) compared with the non‐granulomatous rosacea (NGR) and test the hypothesis that the changes of these profiles in GR would be related with chronic ultraviolet radiation (UVR)‐exposure. Methods Facial skin samples were obtained from 20 patients with GR and NGR (control group). The sections were stained using haematoxylin and eosin, Verhoeff’s elastic stain, and antibodies to TGF‐β, TβRII, TNF‐α, MMP‐1, ‐2 and ‐9. Results The amount of elastotic material was significantly increased in the dermis of GR lesions. Expression of TGF‐β was significantly decreased in the epidermis of GR lesions compared with NGR lesions. In addition, the expression of MMP‐9 was significantly increased in the dermis of GR lesions compared with NGR lesions, especially at the centre of the granuloma on a semi‐quantitative analysis. MMP‐2 expression was also increased in GR lesions, although the difference between the two groups was not statistically significant. Conclusions The results of this study suggest that the increased expression of MMPs in the dermis may participate in granuloma formation of GR in association with UVR.     

Probing lactate secretion in tumours with hyperpolarised NMR

Most tumours exhibit a high rate of glycolysis and predominantly produce energy by lactic acid fermentation. To maintain energy production and prevent toxicity, the lactate generated needs to be rapidly transported out of the cell. This is achieved by monocarboxylate transporters (MCTs), which therefore play an essential role in cancer metabolism and development. In vivo experiments were performed on eight male Fisher F344 rats bearing a subcutaneous mammary carcinoma after injection of hyperpolarised [1‐¹³C]pyruvate. A Gd(III)DO3A complex that binds to pyruvate and its metabolites was used to efficiently destroy the extracellular magnetisation after hyperpolarised lactate had been formed. Moreover, a pulse sequence including a frequency‐selective saturation pulse was designed so that the pyruvate magnetisation could be destroyed to exclude effects arising from further conversion. Given this preparation, metabolite transport out of the cell manifested as additional decay and apparent cell membrane transporter rates could thus be obtained using a reference measurement without a relaxation agent. In addition to slice‐selective spectra, spatially resolved maps of apparent membrane transporter activity were acquired using a single‐shot spiral gradient readout. A considerable increase in decay rate was detected for lactate, indicating rapid transport out of the cell. The alanine signal was unaltered, which corresponds to a slower efflux rate. This technique could allow for better understanding of tumour metabolism and progression, and enable treatment response measurements for MCT‐targeted cancer therapies. Moreover, it provides vital insights into the signal kinetics of hyperpolarised [1‐¹³C]pyruvate examinations. Copyright © 2016 John Wiley & Sons, Ltd.     

Potential roles of follicular dendritic cell-associated osteopontin in lymphoid follicle pathology and repair and in B cell regulation in HIV-1 and SIV infection

Osteopontin is a multifunctional protein with known roles in bone remodeling, wound healing, and normal and pathological immune responses. We showed in microarray studies that osteopontin gene expression is increased in human immunodeficiency virus type 1 (HIV-1)-infected lymphatic tissues after treatment, and we undertook mapping experiments to study osteopontin's possible functions in this context. We discovered species-specific colocalization of osteopontin with the follicular dendritic cell (FDC) network in lymphatic tissues in HIV-1 and simian immunodeficiency virus infections, and we found that changes in FDC-associated osteopontin covary with changes in lymphoid follicles during acute and late stages of infection and in response to treatment. We propose that this localization normally facilitates antibody production and plays a role in B cell abnormalities in infection and in the reconstitution of lymphoid follicles with treatment and that mapping genes identified in microarray studies is a useful experimental approach to gaining a better understanding of function in the context of a particular tissue and disease.     

Incidence and implication of additional chromosome aberrations in acute promyelocytic leukaemia with translocation t(15;17)(q22;q21): a report on 50 patients

Acute promyelocytic leukaemia (APL) is characterized by the translocation t(15;17)(q22;q21). Usually t(15;17) is the sole cytogenetic abnormality, but some patients show other chromosome aberrations in addition to t(15;17). The influence of additional chromosome aberrations on the clinical outcome of patients with t(15;17) is unclear. We have analysed 50 cases of APL carrying the translocation t(15;17). Additional chromosome aberrations were observed in 17/47 patients (36%) studied at initial diagnosis and in all three patients studied at relapse. In nine cases (18%) an additional chromosome 8 and in six cases (12%) an isochromosome of the long arm of the derivative chromosome 17 was observed. Various structural rearrangements in addition to t(15;17) were detected in nine patients (18%). Clinical follow-up data were available for 44 patients studied at diagnosis. A complete remission (CR) was achieved in 34 patients (77%). 10 patients (23%) died within 1 month after diagnosis due to infection or bleeding, eight (24%) relapsed within 10–18 months after initial diagnosis. 28 patients are alive 2–93 months after diagnosis (25 in first CR, two in second and one in third CR) (median follow-up 18.5 months). Bone marrow transplantation was performed in six patients (three in first CR, two in second CR, one in third CR), all are alive and in CR. An influence of secondary chromosome anomalies on prognosis was not observed. However, if a higher rate of long-term remission can be reached, specific secondary chromosome aberrations might turn out to be of prognostic value.     

Experimental validation of geometric and densitometric coronary measurements on the new generation cardiovascular angiography analysis system (caas ii)

Computer-assisted contour detection and videodensitometric cross sectional area assessment of coronary artery obstructions on the CAAS II system were validated in vitro and in vivo by angiographic cinefilm recording and automated measurement of stenosis phantoms (luminal diameter 0.5, 0.7, 1.0, 1.4, 1.9 mm) which were first inserted in a plexiglass model and then serially implanted in swine coronary arteries. “Obstruction diameter” (OD) and “obstruction area” (OA) values obtained from 10 in vitro and 19 in vivo images at the site of the artificial stenoses were compared with the true phantom dimensions. The in vitro assessment of OD yielded an accuracy of 0.00±0.11 mm (correlation coefficient: r = 0.98, y = 0.18 + 0.82x, standard error of estimate: SEE = 0.08), whereas the in vivo measurement of OD gave an accuracy of ?0.01 ± 0.18 mm (r = 0.94, y = 0.22 + 0.82x, SEE = 0.15). The assessment of OA gave an accuracy of ?0.08 ± 0.21 mm² in vitro (r = 0.97, y = 0.08 + 0.99x, SEE = 0.22) and ?0.22 ± 0.32 mm² in vivo (r = 0.95, y = 0.21 + 1.01x, SEE = 0.33). The mean reproducibility was ±0.09 mm for geometric measurements and ±0.21 mm² for videodensitometric assessments, respectively. Thus, due to inherent limitations of the imaging chain, the reliability of geometric coronary measurements is still far superior to videodensitometric assessments of vessel cross sectional areas. © 1993 Wiiey-Liss, Inc.     

A comparison of seasonal changes in the concentrations of androgens in the peripheral blood of wild and domestic ducks

Blood samples taken in monthly intervals over a 2-year period from individually marked wild mallard and Khaki Campbell drakes were assayed for testosterone (T) and 5α-dihydrotestosterone (DHT). In the first year plasma T and DHT were measured simultaneously using a competitive protein binding (CPB) method, while in the second year T (without separation from DHT) was determined with a commercial radioimmunoassay (RIA). The wild mallard drakes showed a bimodal pattern in the annual variation of the T concentrations, one peak coinciding with the reproductive season and the second in autumn. The Khaki Campbell drakes had high T levels in spring, late summer, and in autumn/winter. In some of these birds the depression of the T concentrations usually observed in June and/or July was only slight. In both wild and domestic drakes plasma T and LH concentraitons were linearly correlated. The late autumnal peak of these hormones was not accompanied by an increase in testis weight, in neither wild nor domestic drakes. This peak seems to be related to pair formation. The plasma DHT concentrations of our drakes were higher than those known for mammals. The patterns of the seasonal variations were similar to those of the respective T concentrations. Domestication seems to flatten the seasonal fluctuations of the hormones studied. Maximal values of plasma DHT as well as of plasma LH concentrations were similar in wild and domestic drakes, but in their maximal T levels the domestic drakes by far exceeded the wild ancestor.