Lack of CD 29 (beta1 integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis

Intravascular Lymphomatosis (IL) is a rare and usually aggressive form of non-Hodgkin's lymphoma characterized by the growth of neoplastic cells within vascular lumina that usually presents with skin or central nervous system (CNS) involvement. The mechanism(s) for the selective intravascular growth of this neoplasm remain(s) unexplained. We now report clinical and immunohistologic data on surgical material from 6 cases of IL; in 4 of 6 cases, autopsies were performed. Our IL cases shared the following features: (1) B-cell lineage; (2) lack of skin involvement at presentation; (3) aggressive behavior; and (4) lack of extravascular lymphomatous masses; in addition, 1 case had an associated gastric low-grade MALT lymphoma. We studied by immunohistochemistry formalin-fixed, paraffin-embedded sections with monoclonal antibodies to molecules known to be involved in lymphocyte and endothelial adhesion phenomena, that is, CD29 (beta1 integrin subunit), CD43 (leukosialin), CD44 (H-CAM), CD54 (ICAM-1), embryonal N-CAM (e-NCAM), and EMA (episialin). In all cases, the surfaces of IL aggregates reacted for CD44 but were consistently negative for CD29; also absent was CD54. Conversely, the integrity of the endothelial cells was underscored by their even reactivity for CD29, CD44, and CD54. Given that CD29 is currently regarded as critical for lymphocyte trafficking in general and for transvascular migration in particular, and CD54 is also involved in transvascular lymphocyte migration, we conclude that their consistent absence in IL may contribute to its intravascular and disseminated distribution pattern. The rather frequent association of IL with various conventional lymphomas is known; yet, one of our cases appears to be the first report of IL associated with a low-grade MALT lymphoma.     

Recognition of a novel naturally processed, A2 restricted, HCV-NS4 epitope triggers IFN-gamma release in absence of detectable cytopathicity

Using short term CTL lines derived from HLA A2/K^b transgenic mice and IFN-gamma release assays we demonstrate that the NS4.1769 epitope, is generated from natural processing of the NS4 antigen, and presented in the context of the A2/K^b molecules. Interestingly, T cell recognition of the naturally processed form of the NS4.1769 epitope was associated with significant IFN-gamma release, but no direct cytolytic activity. Epitopes of this phenotype might be of interest, in terms of therapy of chronic HCV infection by associating the benefit of localized lymphokine release with low or absent direct cytopathicity.     

Anisakis simplex, a relevant etiologic factor in acute urticaria

Del Pozo MD, Audícana M, Diez JM, Muñoz D, Ansotegui IJ, Fernández E, García M, Etxenagusia M, Moneo I, Fernández de Corres L. Anisakis simplex , a relevant etiologic factor in acute urticaria.
Anisakis simplex , a parasite of fish and cephalopods, can induce IgE-mediated reactions. This study aimed to determine the etiologic role of A. simplex in patients affected by urlicaria/angioedema 'AE' or anaphylaxis. We studied 100 adult subjects suffering acute episodes of urticaria/AE, by anamnesis, prick tests with A. simplex and fish-mix extracts, and total and specific IgE to both A. simplex and cod. The following criteria of A. simplex allergy were considered: 1' urticaria/AE within 6 h after fish ingestion; 2' specific IgE to A. simplex; 3' positive prick test to A. simplex extract; 4' exclusion of other suspected causes. Double-blind, placebo-controlled food challenge was not carried out because ethical considerations forbid challenge with a parasite. Specific IgE to A. simplex '<0.7 kU/1' was found in 22 subjects, but only eight were diagnosed as having A. simplex allergy. Other allergens were involved in 37 patients, and 55 cases were considered idiopathic. Specific IgE to fish '<0.7 kU/1' was found in two patients, but only one was diagnosed as having fish allergy. We concluded that A. simplex is an important etiologic factor in acute urticaria. We suggest that it should be considered in cases of urticaria/AE or anaphylaxis, especially after fish ingestion.     

Long-term social isolation in the rat induces opposite changes in binding to alpha 1- and alpha 2-adrenoceptors in the brain and vas deferens

Rats isolated at the time of calcification of the incisors show, after 14-18 months of social deprivation, an increased number of alpha 1-adrenoceptors labeled with [3H]WB 4101, both in the striatum and in the vas deferens, as well as a decreased number of alpha 2-adrenoceptors labeled with [3H]-clonidine in the vas deferens. Social isolation does not, however, modify the density of [3H]clonidine binding sites in the cerebral cortex. The functional state of alpha-adrenoreceptors in the vas deferens from isolated rats appears to correlate with the binding studies since the isolated tissue is hypersensitive to the contractile effect of exogenous noradrenaline and subsensitive to the inhibitory effect of clonidine on the electrically stimulated preparation.     

Cutaneous angiomyolipoma: a case report and literature review

Angiomyolipoma is a lesion usually observed in the kidney of patients with tuberous sclerosis. Extrarenal sites are very unusual with sporadic cases in internal organ, soft tissue and skin (fifteen cases have been described in this site). Herein we describe an adding case located on the ear in 58-year-old man reviewing the pertinent literature. The main diagnostic differential criteria are also discussed.     

Distribution of the serotonin 2C (5HT2C) receptor gene -759C/T polymorphism in patients with schizophrenia and normal controls

BACKGROUND: In patients with schizophrenia, the percentage of patients with diabetes has been found to be twice that of the normal population. The risk factors for this higher rate are unknown, although dietary, lifestyle, and genetic factors have all been suggested. Recently, a polymorphism (-759C/T) in the serotonin 2C (5HT2C) receptor promoter region has been associated with the development of diabetes in a normal control population, with the frequency of the T allele being higher in subjects without diabetes. AIM: To determine whether the distribution of the -759C/T polymorphism of the 5HT2C receptor is different among patients with schizophrenia and normal controls. METHODS: DNA from 100 patients with schizophrenia and 81 normal controls were analyzed for the 5HT2C receptor -759C/T polymorphism to determine its allelic frequencies in these two groups. RESULTS: Using a chi-squared analysis, no statistical differences in the distribution of C alleles and T alleles were found between the two groups (P=0.2931). CONCLUSIONS: Patients with schizophrenia have a higher risk for developing diabetes than the general population. We did not find a higher distribution of the -759T allele of the 5HT2C receptor in normal controls compared with in patients with schizophrenia. This suggests the higher prevalence of diabetes in schizophrenia is not due to this polymorphism.     

Cotrimoxazole therapy ofToxoplasma gondii encephalitis in AIDS patients

Twenty-four consecutive HIV-positive patients affected byToxoplasma gondii encephalitis received trimethoprim-sulfamethoxazole (cotrimoxazole) as acute-phase treatment. Two dosage regimens of cotrimoxazole were used: 40 mg/kg/day (12 patients) or 120 mg/kg/day (12 patients) of total compound (trimethoprim plus sulfamethoxazole). Clinical and radiological responses to treatment were evaluated, and the product-limit method for survival data analysis was used. Eighteen of 24 patients showed both a clinical and radiological response (75 % response rate). There were no differences in response rates between patients receiving the two dosage regimens of cotrimoxazole. Adverse reaction consisted of leukopenia (two cases) and skin rash (three cases) which led to the discontinuation of the drug in one case. These results suggest that a randomized, controlled clinical trial should be carried out comparing cotrimoxazole versus sulfadiazine-pyrimethamine in AIDS patients withToxoplasma gondii encephalitis.Deceased.     

Selective sequestration of X4 isolates by human genital epithelial cells: Implication for virus tropism selection process during sexual transmission of HIV

X4 and R5 HIV strains are present in the semen of men infected with HIV but R5 isolates are transmitted preferentially. The role of human epithelial cells in this selection is addressed. Three human cervical cell lines-CaSki, SiHa, and HEC1A-and normal human vaginal cells from HIV-negative donors were characterized for HIV receptor expression and incubated with X4 and R5 laboratory-adapted strains or primary isolates. The infection was assessed by detection of intracellular HIV DNA. The three cell lines were shown to express on their surface the CXCR4 and GalCer molecules, but not the CD4 and CCR5 ones. The three cell lines and normal human vaginal cells were found to be selectively permissive to X4 HIV entry; the preincubation of the cell lines with rhSDF-1 inhibited this infection. The detection of the intracellular proviral DNA in the cell lines and in normal human vaginal cells demonstrated a selective integration of X4 strains. Additional experiments showed that no extracellular RNA was detected in the supernatants of HEC1A cells infected by X4 isolates either after 18 days of culture or after incubation with PHA-stimulated PBMCs and that no transmission occurred after co-culture between infected HEC1A cells and PHA-stimulated PBMCs. These results suggest specific sequestration of X4 strains by genital epithelial cells, which could explain, at least in part, the HIV tropism selection process during sexual intercourse.     

Multiple pathways of cell invasion are regulated by multiple families of serine proteases

The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that control cell spreading. A number of data indicate that such a `grip and go' process may be performed by an enlarging series of cell membrane-associated serine proteases and serine protease receptors, which provide the invasive cells with a functional unit (the protease and its receptor), able to mediate cell-substratum adhesion through specific receptor domains, to proteolytically degrade ECM and to deliver into the cell signals that up-regulate the expression either of the protease/receptor complex, or of other adhesion molecules, such as integrins. There is evidence that some proteases and protease receptor expression are under the control of tumor hypoxia, which is the result of an imbalance in oxygen supply and demand. The urokinase-type plasminogen activator (u-PA) receptor (u-PAR) is under hypoxic control and cooperates with other serine proteases of the blood coagulation pathways that may extravasate in the tumor milieu as a result of hypoxia-simulated increase of vessel permeability. Other serine proteases and their receptors cooperate with the cell-associated fibrinolytic system to promote cell invasion. Among these, tissue factor and its ligand coagulation factor VII, thrombin and its protease-activated receptors, and type II trans-membrane serine proteases seem to play a crucial role. This Review takes into consideration the complex scenario of the single serine proteases and related receptors that are involved in cell invasion, as well as the protease receptor/adhesion molecule interplay which is necessary to focus the cell surface-driven proteolysis where adhesion provides a grip to the invading cell. This revised version was published online in July 2006 with corrections to the Cover Date.