Hydrodynamic Function of Second Generation Porcine Bioprosthetic Heart Valves

The hydrodynamic function and leaflet dynamics of second generation porcine valves prepared with low- or zero-pressure fixation have been studied and compared to first generation porcine bioprostheses, bileaflet, and tilting disc mechanical valves. The Carpentier-Edwards Supra-Annular and Hancock II valves showed lower pressure drops than the Medtronic Intact valve and first generation porcine valves, and comparable overall energy losses to mechanical valves at normal cardiac outputs. Only the zero-pressure fixed Intact valve showed synchronous leaflet opening. Delayed leaflet opening and high opening pressures were found in both low- and high-pressure fixed porcine valves. All porcine bioprostheses showed high open leaflet bending strains. Fixation of valve leaflets with "near zero" pressure fixation and a more physiological neutral geometry is necessary to ensure synchronous leaflet opening at low flows and a reduction in commissural bending strains.     

An Alzheimer's Disease-Relevant Presenilin-1 Mutation Augments Amyloid-Beta-Induced Oligodendrocyte Dysfunction

研究表明,家族性阿尔茨海默病(FAD)患者处于无症状或临床前阶段时,脑白质即出现病理改变.此种改变在髓鞘破坏及阿尔茨海默病(AD)病理生理中的作用有待进一步研究阐明.笔者前期研究证实,三重转基因AD小鼠(人淀粉前体蛋白基因的Swedish突变,早老素-1 M146V (PS1M146V)敲入突变及tauP301L突变)...     

Decrease in intrahepatic CD56+ lymphocytes in gastric and colorectal cancer patients with liver metastases

Gulubova M, Manolova I, Kyurkchiev D, Julianov A, Altunkova I. Decrease in intrahepatic CD56⁺ lymphocytes in gastric and colorectal cancer patients with liver metastases. APMIS 2009; 117: 870–9. The aim of the study was to examine the main intrahepatic lymphocyte subpopulations, namely CD3⁺ lymphocytes, natural killer (NK)‐like T lymphocytes (NKT) expressing the CD3⁺ CD56⁺ phenotype, CD56⁺ NK cells, CD4⁺, and CD8⁺ T cells in livers of patients with gastric and colorectal cancer with and without hepatic metastases. The proportion of each lymphocyte subset was determined in 34 patients with gastric or colorectal cancer (18 with and 16 without liver metastasis) by two‐color flow cytometry after extraction of hepatic mononuclear cell fraction. The distribution of lymphocyte subpopulations in selected areas of liver metastases and adjacent liver tissue was evaluated using immunohistochemistry for CD4, CD8, and CD56. Flow cytometry analysis revealed a significant decrease in the proportion of CD3⁺ CD56⁺ cells in metastatic livers, but not in nonmetastatic livers (11.9 ± 10.3 vs 24.2 ± 13.6%, p = 0.02). The percentage of intrahepatic CD3^?CD56⁺ cells was also decreased in patients with metastases compared to those without (10.1 ± 11.6 vs 16.6 ± 8.9%, p = 0.039). Immunohistochemically, three types of lymphocytes (CD4⁺, CD8⁺, and CD56⁺) were present in the metastatic tissue, although the number of CD56⁺ cells was almost twice lower. We found a low prevalence of tumor‐infiltrating CD4⁺, CD8⁺, and CD56⁺ cells in livers with multiple metastases, whereas in cases with solitary metastasis a higher degree of lymphocyte infiltration was observed. The number of CD3^?CD56⁺ and CD3⁺ CD56⁺ cells was decreased in metastatic livers compared to those unaffected by metastases. Therefore the prevalence of tumor‐infiltrating lymphocytes seems to be related to the progression of metastatic liver disease. Depletion of hepatic innate lymphocytes may reveal susceptibility to metastatic liver disease and could be a reason for the escape of metastatic cells from the mechanisms of liver immune control.     

Differential expression of LAMPs and ubiquitin in human thymus

Lysosome‐associated membrane proteins 1 and 2 (LAMP‐1 and LAMP‐2) are implicated in a variety of normal and pathological processes. LAMP‐2 is proposed to participate in chaperone‐mediated autophagy. Autophagy regulates T‐lymphocyte homeostasis by promoting both survival and proliferation. The biological importance of this process in the thymic gland and especially the involvement of LAMPs are far from being elucidated. The aim of the study was to examine the parallel expression of LAMPs and ubiquitin, a key molecule in autophagy, in normal human thymic glands and thymomas. The immunohistochemical expression of both markers was compared with that of cyclin D1 – an important regulator of cell cycle progression. Novel evidence for differential expression of LAMPs and ubiquitin is presented. Most Hassal's corpuscules in thymoma were negative for LAMPs, but positive in normal thymus. Both lymphocytes and epithelial cells in pathological thymus showed higher intensity for LAMP‐2 compared with LAMP‐1. In thymoma, ubiquitin was more intensively positive in these cell types compared with the normal thymus, suggesting activated autophagy in the course of this pathological state. A deregulation in cyclin D1 expression in thymoma is also reported. The functional importance of these molecules in autoghagy accompanying normal and pathological processes in the thymic gland is reviewed.     

Repair of chronic tympanic membrane perforations with fibroblast growth factor

A number of angiogenic growth factors have been shown to accelerate wound healing. Previous work has demonstrated that topical application of epidermal growth factor is effective in healing chronic tympanic membrane perforations in an animal model. Theoretically, fibroblast growth factor may result in a superior healed membrane through preferential stimulation of the fibroblasts within the middle layer of the tympanic membrane. To test this hypothesis, the effects of exogenously applied fibroblast growth factor on the chronically perforated tympanic membrane were evaluated. A buffered solution of fibroblast growth factor (25 μl of fibroblast growth factor, 0.2 mg/ml) was administered to a Gelfoam pledget placed over chronic tympanic membrane perforations in chinchillas. Control ears were treated with Gelfoam and the buffer solution only. Complete closure of the tympanic membrane perforation was observed in 81% (13 of 16) of the fibroblast growth factor - treated ears, but in only 41% (7 of 17) of the controls (p = 0.05). Healing took place gradually, requiring an average of 4 weeks for the fibroblast growth factor - treated and 6.5 weeks for the control ears that healed. The relatively high healing rate for the control group does not imply that the pretreatment perforations were not chronic, rather there appears to be some efficacy to the control protocol of repeated applications of Gelfoam and buffer. A histologic analysis of the fibroblast growth factor - healed eardrums immediately after closure demonstrated hypertrophy of the squamous and fibrous layers of the tympanic membrane. Over time, the eardrum thinned to reach proportions similar to those of the normal tympanic membrane, including the presence of a substantial middle fibrous layer. A screening ototoxicity study revealed no structural damage to the organ of Corti after growth factor treatment. To assess the potential for systemic toxicity, blood and peripheral tissues were analyzed for radioactivity at time points during a 48-hour period after application of 25 μl of ¹²⁵I-fibroblast growth factor to the perforated tympanic membrane. More than 78% of the radioactivity remained at the application site. Given the tiny original dosage, the small fraction absorbed systemically is minuscule and highly unlikely to induce adverse effects in light of published toxicity data. On the basis of these promising safety and efficacy data in the chinchilla model, clinical trials of fibroblast growth factor in repair of chronic tympanic membrane perforations in human beings are being initiated. (Otolaryngol Head Neck Surg 1996;115:538-47.)     

Growth factor action in neural crest cell diversification

At the onset of their migration into the embryo, many neural crest cells are pluripotent in the sense that they have the capacity to generate progeny that consist of more than one cell type. More recently, we have found that there are pluripotent neural crest cell-derived cells even at sites of terminal differentiation. These findings support the notion that cues originating from the microenvironment, at least in part, direct neural crest cell type specification. Based on the rationale that growth factors that are known to support survival of neural crest cell derivatives may have additional functions in progenitor cell development, we have examined the action of pertinent growth factors. Trophic, mitogenic, antiproliferative and differentiation promoting activities were found. Stem cell factor (SCF) is trophic for pluripotent neural crest cells. Contrary to expectation, SCF plus a neurotrophin, rather than SCF alone, is trophic for committed melanogenic cells. Basic fibroblast growth factor (bFGF) is mitogenic both for pluripotent cells and committed melanogenic cells. However, the cells become dependent on another factor for survival. Whereas any neurotrophin tested can rescue bFGF-activated pluripotent neural crest cells, the factor that rescues melanogenic cells remains to be determined. Transforming growth factor β1 (TGF-β1) is a powerful antimitotic signal for all neural crest cells that overrides the bFGF/neurotrophin proliferative signal. Furthermore, SCF promotes differentiation of neural crest cells into cells of the sensory neuron lineage. Neurotrophin-3 (NT-3) specifically promotes high affinity uptake of norepinephrine by neural crest cells and is thus thought to play a critical role in the differentiation of sympathetic neuroblasts. In summary, our data indicate that neurotrophins and other pertinent growth factors affect survival, proliferation and differentiation of neural crest cells at multiple levels and in different lineages. Moreover, our findings emphasise the importance of the concerted action of combinations of growth factors, rather than of individual factors.     

Determinants of condom use among HIV-positive men who have sex with men

The main objectives of this study were to identify the determinants of condom use among HIV-positive men having anal sex with HIV-negative men or men of unknown HIV status and moderators of the intention-behaviour relationship. A cohort of 237 sexually active HIV-positive men having sex with men was followed over a period of six months. The cognitive variables measured were guided by an extended version of the theory of planned behaviour. Results indicated that past behaviour (odds ratio [OR] = 9.75; 95% confidence interval [CI]: 4.48-21.26), intention (OR = 3.13; 95% CI: 1.25-7.81), self-efficacy (OR = 3.62; 95% CI: 1.40-9.37) and use of sex drugs (OR = 0.16; 95% CI: 0.06-0.45) contributed to the prediction of 100% condom use. Self-efficacy also interacted with intention as a significant moderator of the intention-behaviour relationship (OR = 20.96; 95% CI: 2.90-151.51). Interventions promoting condom use should increase self-efficacy to use condoms and target users of sex drugs.