Proangiogenic cytokines (bFGF and VEGF) in BALF from two different lung segments examined by high resolution computed tomography (HRCT) in patients with sarcoidosis

The aim of the study was to evaluate the concentrations of bFGF and VEGF in double BAL (2 x 120 ml) from two different lung segments: (s.A) from upper lobe with the most and (s.B) from lower lobe with the least extensive involvement estimated by high resolution computed tomography (HRCT). Examined group consisted of 28 sarcoid patients with homogeneous, regular distribution of nodular opacities in conventional chest X-ray (14 F, 14 M aged 19-54). Eleven healthy volunteers served as controls. In patients with sarcoidosis we observed the significantly higher levels (p < 0.01) of bFGF (1.79 pg/ml, 1.48 pg/ml) and VEGF (107.5 pg/ml, 109.7 pg/ml) in BAL from s.A and s.B respectively in comparison with BAL from lung segments Abis and Bbis in control group (bFGF: 0.75 pg/ml, 0.47 pg/ml and VEGF: 33.7 pg/ml, 43.9 pg/ml respectively). bFGF in BAL from s.A in active sarcoidosis was higher than in s.A and s.B in non-active sarcoidosis. Concentrations of bFGF in BAL from both s.A and s.B correlated positively with CD4/CD8 ratio and absolute number of lymphocytes, CD4 cells and lymphocytes HLA-DR estimated in BAL from these lung segments. We conclude that bFGF and VEGF may be involved in sarcoidosis pathogenesis and bFGF may be useful in estimation of sarcoidosis activity.     

Unrestricted recognition of class I neodeterminants generated by exon shuffling

We and others have previously reported that homologous exchange of alpha 1 or alpha 2 domains between different alleles led to loss of most determinants recognized by cytotoxic T lymphocytes (CTL) raised against the parental H-2 class I antigens. Here we demonstrate that exchange of alpha 1 or alpha 2 domains between the Kk and Kd allele results in the formation of neodeterminants against which allospecific CTL can be generated in responder mice of various related and unrelated H-2 haplotypes. In fact, only CTL against the neodeterminants on the hybrid molecules were found and none against the parental Kk and Kd determinants. In addition our data show that recognition of the neodeterminants is H-2 unrestricted. These findings suggest that in the hybrid molecules the basic structure of a major histocompatibility complex molecule has been preserved although most parental allodeterminants on the alpha 1 and alpha 2 domains have been modified.     

Concurrent infections ofTrichinella spiralis andToxoplasma gondii in mice

Concurrent infections with two parasites: a nematode,Trichinella spiralis, and a protozoon,Toxoplasma gondii, were investigated. Antibody production (total immunoglobulin and IgM) was similar in double and single infections. However, the number ofToxoplasma cysts in the brains of mice infected withTrichinella and challenged 1–6 weeks later withToxoplasma was higher than in mice infected withToxoplasma alone, while mice infected withToxoplasma and challenged 4–14 days later withTrichinella had lower worm burdens in the intestine than animals infected withTrichinella alone. Greater loss in body weight was observed in mice infected with both parasites than in those infected with either parasite alone.     

Microvascular structural entropy: A novel approach to assess angiogenesis in pituitary tumors

Entropy, a measure of the degree of disorder in a system, has recently been used in different morphologic studies to quantify regularity. Our aims were (a) to study the structural organization of the microvascular bed in prolactin (PRL)-producing adenomas and carcinomas, the most vascularized of pituitary tumors, by assessing microvascular structural entropy (MSE), and (b) to determine whether the degree of disorder of the capillary bed correlates with tumor cell proliferation as estimated by MIB-1 labeling, microvessel density (MVD), the most widely used method of quantifying blood vessel formation, and various clinicopathologic parameters (gender, age, tumor size and invasiveness). The morphometric study demonstrated statistically significant differences in MIB-1 labeling, MVD, and MSE between PRL-producing adenomas and carcinomas. Unlike MIB-1 labeling index (PRL-producing adenomas 1.5±0.27; carcinomas 15.0±4.04) and MVD (PRL-producing adenomas 2.7±0.34; carcinomas 4.2±0.72), the MSE values were significantly higher in adenomas (171.5±25.37) than in carcinomas (67.9±17.45). These results indicate that PRL-producing carcinomas have a less chaotic distribution of vessels than benign adenomas. In contrast to a lack of correlation between, microvessel density and other morphometric parameters, a strong negative correlation was found between MSE and MIB-1 labeling index (r=0.511, p=0.003). It thus appears that regular, less chaotic microvascular geometry contributes to increased proliferative activity in PRL cell tumors. Analysis of MSE may provide an independent parameter of tumor behavior, and contributes to a better understanding of the role of microvasculature in pituitary tumor progression.     

Neutralizing antibodies in gene-defective hosts

In a host with a normal immune system and a complete gene defect, the nondefective gene product will be immunogenic. Consequently, neutralizing antibodies against the respective protein can arise either 'spontaneously' or after immunization, as shown in patients and in animal models, such as knockout mice. Accordingly, patients with X-linked or homozygous autosomal gene defects are at risk of developing neutralizing antibodies, in particular after protein substitution or gene therapy. This Review compares and exemplifies the various genetic and immunological contexts that lead to 'neutralizing and generated by gene defect' or 'nagged' antibodies, and outlines implications and solutions for therapeutic strategies.     

A sensitive bioassay for chicken interleukin-18 based on the inducible release of preformed interferon-gamma

Conventional tests for measuring the biological activity of chicken interleukin (IL)-18 require primary chicken spleen cells. We now describe a sensitive bioassay that is based on interleukin-18-induced release of interferon (IFN)-gamma by a permanent chicken cell line. In B19-2D8 cells, cytoplasmically stored interferon-gamma is quickly secreted in response to interleukin-18 exposure.     

The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth

Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of alpha/beta-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase.