HTLV infection among Italian intravenous drug users and North African subjects detected by the polymerase chain reaction and serological methods

The relevance of coagulation abnormalities in ischemic stroke remains uncertain. The purpose of this study was to identify abnormal patterns of coagulation in established ischemic stroke. We measured coagulation parameters in 86 patients with acute ischemic stroke: 10 lacunar, 55 atherothrombotic and 21 cardioembolic. Statistical comparisons were made between different stroke groups and between all stroke patients and 60 healthy controls. A decrease in functional antithrombin III and plasminogen and an increase in thrombin-antithrombin III complexes, total protein S, tissue plasminogen activator, plasminogen activator inhibitor and D-dimer were observed in the stroke group (p < 0.05). A positive correlation was found between tissue plasminogen activator and thrombin-antithrombin III levels in cardioembolic stroke (p < 0.05). Protein C levels showed significant differences between the three groups, and in the cardioembolic group they were lower than in controls (p < 0.05). Antiphospholipid antibodies were positive in two cases. We conclude that activation of coagulation and fibrinolytic pathways was observed during the acute phase of ischemic stroke. Protein C activity is different in the three types of strokes analyzed, and higher levels seem to be associated with lacunar lesions. Antiphospholipid antibodies do not seem to play an important role in the pathogenesis of stroke in a nonselected population.     

Human effector memory T cells express CD86: a functional role in naive T cell priming

The glycoprotein CD86 expressed on APCs provides a costimulatory signal necessary for an efficient activation of naive T cells. In contrast, there is controversy about the condition of expression and the function of CD86 on T cells. In this study, we have analyzed the phenotype and the biological activity of CD86+ T cells generated from human PBMC. Results show that CD86 expression on T cells is induced by long term stimulation via CD3 and IL-2R and is down-regulated as the cells become quiescent. The CD86-expressing cells are memory effector T cells: 1) they express CD45RO and high levels of the activation markers CD25, CD54, and HLA-Dr; 2) they selectively express CD30, CD40-ligand, and CD70; and 3) in response to stimulation, most of them produce IFN-gamma before dying by apoptosis. We then analyzed whether CD86 expressed on T cells is functional. Results show that paraformaldehyde-fixed CD86+ T cells enhance the proliferation and production of IFN-gamma by anti-CD3 mAb-stimulated naive T cells and induce proliferation of resting allogenic T cells. All these effects are prevented by neutralizing anti-CD86 mAbs. In contrast, we report no autocrine effect of CD86 in CD86+ T cell activation. In conclusion, these data show that human memory effector T cells express a functional form of CD86 that can costimulate naive T cell responses.     

Polymorphisms of Dopamine Receptor Genes and Parkinson’s Disease: Clinical Relevance and Future Perspectives

Parkinson’s disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the midbrain. PD is clinically characterized by a variety of motor and nonmotor symptoms, and treatment relies on dopaminergic replacement. Beyond a common pathological hallmark, PD patients may present differences in both clinical progression and response to drug therapy that are partly affected by genetic factors. Despite extensive knowledge on genetic variability of dopaminergic receptors (DR), few studies have addressed their relevance as possible influencers of clinical heterogeneity in PD patients. In this review, we summarized available evidence regarding the role of genetic polymorphisms in DR as possible determinants of PD development, progression and treatment response. Moreover, we examined the role of DR in the modulation of peripheral immunity, in light of the emerging role of the peripheral immune system in PD pathophysiology. A better understanding of all these aspects represents an important step towards the development of precise and personalized disease-modifying therapies for PD.     

The value of cervical mediastinoscopy combined with anterior mediastinotomy in the peroperative evaluation of bronchogenic carcinoma of the left upper lobe

METHODS: From January 1990 to July 1994, 85 patients who were otherwise thought to have an operable tumour within the left upper lobe underwent left anterior mediastinotomy supplemented by cervical mediastinoscopy in 75 cases. This combined approach allowed assessment of nodal involvement within the superior and anterior mediastinal areas, the detection of direct tumour invasion into the mediastinum and the determination of resectability by bidigital examination of the area around the aortic arch and sub-aortic fossa. RESULTS: It was found that 27 (31.8%) patients were inoperable, either because of nodal involvement at cervical mediastinoscopy (4 patients) or because of extension into the mediastinum at left anterior mediastinotomy (14 patients), or because of positive results from both methods (9 patients). The inoperability determined by this examination for patients with adenocarcinoma (8/18, 44.4%) is higher than for patients with squamous carcinoma (12/52, 23.1%). All of the 58 patients with negative findings proceeded to thoracotomy and complete resection was possible in 54 patients (93.1%). CONCLUSION: We conclude that this combined approach is better than using either technique alone in the preoperative staging and the evaluation of resectability of left upper lobe tumours.     

Effect of cell density on cytotoxicity of ether lipid analogues in variants of B16 murine melanoma

Ether lipids are defined here as analogues of naturally occurring lysophosphatidylcholines with cytotoxic activity against neoplastic cells. The activity of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET18OMe) and 3-hexadecylmercapto-2-methoxymethyl-propyl-1-phosphocholine (Ilmofosine^®) (BM 41.440) was tested in variants of B16 murine melanoma, grown in adhesion cultures (B16F1 with low metastatic potential; B16F10 and B16BL6 with high metastatic potential). Cytotoxicity was evaluated by counting the cells that survived after 24h of drug exposure. Cholesterol, sphingomyelin, total phospholipid and phosphatidylcholine levels were determined. After 24 h of drug exposure, cultures of the B16BL6 variant contained a larger number of cells, especially when high drug concentrations (100–250 μM) were used, than cultures of the B16F1 and B16F10 variants. The sensitivity of ET18OMe of the three variants was evaluated at different cell densities (at each density the dose was equalized per number of cells/well; 0.1 μmol/10⁶ cells/well). In B16F1 and B16F10 cultures the dose-response curve was not affected by the number of cells/well, while in B16BL6 no more than 20% of the cells were killed at all cell densities measured. A linear relationship was noted between cell density and cholesterol/phospholipid and sphingomyelin/phosphatidylcholine ratios in the resistant variant B16BL6, confirming that lipid composition modulates the cytotoxic activity of ether lipids.     

High Knudsen number fluid flow at near-standard temperature and pressure conditions using precision nanochannels

Gas flows over a wide range of Knudsen numbers (~0.5–10) are studied using silicon nanochannel arrays with slit-shaped pores. The pore sizes of the silicon nanochannel arrays range from micrometer to sub-10-nm scales. The flows are generated under conditions of room temperature and near-atmospheric pressure (~22°C and ~101–115 kPa) and span the continuum flow, continuum-slip flow, transition flow and free-molecular flow regimes. The measured flow rates of helium, argon and carbon dioxide are in good agreement with a theoretical model (Unified Slip Model) proposed by Beskok and Karniadakis (Nanoscale Microscale Thermophys Eng 3:43–77, 1999).