Upregulation of CXCR1 by proliferating cells in patients with lymphoproliferative disease of granular lymphocytes.

The expression and the functional activities of different chemokine receptors (CC motif: CCR1, CCR2, CCR3, CCR5, CCR6; CXC motif: CXCR1, CXCR2, CXCR3, CXCR4, CXCR5) were investigated in 12 patients with lymphoproliferative disease of granular lymphocytes (LDGL). Six patients were characterized by the proliferation of CD3+ve GL and six patients by the expansion of CD3-ve GL. The interleukin 8 (IL-8/CXCL8) receptor CXCR1 was expressed in 12/12 patients, the CXCR4 in 6/12 patients (four CD3+ve and two CD3-ve) and the CXCR3 in 3/12 patients (one CD3+ve and two CD3-ve).

A four coil exposure system (tetracoil) producing a highly uniform magnetic field.

We propose a magnetic field exposure system (tetracoil) for in vitro and in vivo experiments, composed of two couples of circular coils satisfying a spherical constraint, whose characteristics are chosen in order to maximize the uniformity region of the magnetic field. Analytical calculations and computer simulations show that our system, as compared to the other most largely used magnetic field exposure systems, represents an optimal compromise in terms of field uniformity, accessibility for biological experiments, and ratio between overall dimension and uniformity region.

Applied clinical immunology in sarcoidosis.

Staging of sarcoidosis needs a synthesis of clinical features, histology, radiology, biochemical changes, and immunologic aberrations to distinguish this disease from nonspecific sarcoid-tissue reactions. The main aim of this report is to offer readers an overview on immunologic markers that have been evaluated in the last years with the ultimate goal of relating their determination to the management of the disease. The first part is devoted to immunologic markers that have been proposed to define the activity of the T-cell component of the sarcoid inflammatory process.

T-lymphocytes and cytokines in sarcoidosis.

In the last few years, a number of reports have clearly shown that pulmonary T lymphocytes have evolved a number of effector mechanisms to respond to foreign antigens, ranging from direct cytotoxicity mechanisms to secretion of lymphokines, that have the ability to activate themselves or other pulmonary immunocompetent cells. Furthermore, there is also evidence that lung T cells may have a role in the immunopathogenetic mechanisms taking place in the lung of most immune-mediated diffuse lung disorders. In this paper, we will review the current concepts on the recruitment, homing, and activity of T lymphocytes in the lower respiratory tract of patients with sarcoidosis.

Complement receptor 1 gene polymorphisms in sarcoidosis.

Sarcoidosis is likely to result from exposure of genetically susceptible hosts to environmental agents. Erythrocyte (E) complement receptor 1 (CR1) is a membrane protein mediating the transport of immune complexes (ICs) to phagocytes, and at least three polymorphisms on the CR1 gene are related to erythrocyte surface density of CR1 molecules, in turn related to the rate of IC clearance from circulation. We hypothesized that sarcoidosis could be associated with increased frequency of the CR1 gene alleles coding for reduced CR1/E ratio.

Gene expression profile analysis by DNA microarrays: a new approach to assess functional genomics in diseases.

A biologically based and potentially powerful way to characterize human diseases has arisen from the new science of genomics. One of the methodologies to provide a systematic way to observe and characterize gene expression programs is the DNA microarrays (also called gene chips). This modern genomic analysis tool shows the promise of providing an unbiased approach to detecting biologically relevant differences within clinically similar diseases.

Determinants of the cytotoxicity of irinotecan in two human colorectal tumor cell lines.

Purpose: Irinotecan is a drug of the camptothecin family that has proven activity in advanced colon cancer, with about 20% responses in untreated as well as in 5-fluorouracil-resistant tumors. Irinotecan is considered as a prodrug which needs to be activated to SN-38 by carboxylesterases to become able to interact with its target, topoisomerase I. The work reported here intended to identify the determinants of the cytotoxicity of irinotecan in two human colorectal tumor cell lines, LoVo and HT-29, at the level of the target of the drug and at the level of the availability of the active metabolite to the target.

First report of the Italian register for diffuse infiltrative lung disorders (RIPID).

RIPID was established in 1998 as a joint project of the major Italian scientific societies for Respiratory Medicine, with the aim to create an Italian Register on diffuse infiltrative lung disorders that can provide the basis for epidemiological and clinical studies of adequate sample size. In the period from May 1998 to December 2000, 1,382 cases were submitted from 54 Centers in 15 regions of Italy, 54.2% males (mean age +/- SD 50.

Oxaliplatin: available data in non-colorectal gastrointestinal malignancies.

Oxaliplatin is a third-generation platinum compound which has proven its efficacy alone or in combination with 5-fluorouracil (5-FU) and/or new anticancer drugs in advanced colorectal cancer. Compared to the amount of available data in this cancer, little is known about the use of oxaliplatin in non-colorectal gastrointestinal malignancies. (1) The preclinical activity of the drug alone or in combination; (2) the phase I studies (oxaliplatin alone or in combination with irinotecan, raltitrexed, gemcitabine, folinic acid and 5-FU); (3) the phase II studies developed in gastric, pancreatic, biliary tract, hepatocellular carcinoma and malignant mesothelioma; and (4) some of the ongoing trials with regard to non-colorectal gastrointestinal malignancies are reviewed in this paper.

Proton magnetic relaxation in bone marrow related to age and bone mineral density: low-resolution in vitro studies.

Detailed analysis of proton spin-spin and spin-lattice relaxation behaviors of the bone marrow in the presence of trabecular bone network was performed at low-resolution (B(0) = 0.496T) on rat vertebrae specimens deprived of spinal cord. Two groups of samples, from young and old healthy animals, were investigated before cellular necrosis had started.

Efficacy of 3'-azido 3'deoxythymidine (AZT) in preventing HTLV-1 transmission to human cord blood mononuclear cells.

The present study investigated the effect of 3'-azido 3'deoxythymidine (AZT) treatment on in vitro infection of human cord blood mononuclear cells (CBMCs) exposed to HTLV-1 by cocultivation with the MT-2 cell line. Cultures of CBMCs were grown in IL-2 and were either left untreated or were treated with concentrations of AZT ranging from 0.0078 to 32 microM.

Effect of 3,5,3'-triiodo-L-thyronine on amino acid accumulation and membrane potential in Sertoli cells of the rat testis.

The purpose of this study was to investigate the effect of T3 on amino acid accumulation and on the membrane potential of Sertoli cells of immature rat testes. Testes of pre-pubertal and pubertal rats were pre-incubated (30 min) in Krebs-Ringer bicarbonate buffer and incubated in the presence of [14C]methylaminoisobutyric acid with and without T3 for 15, 45 and 60 min. The hormone (10(-6) M and 10(-7) M) significantly stimulated amino acid accumulation in 6 and 13-day old rat testes but did not have any effect in neonatal and pubertal animals.

Cytokine and chemokine blockade as immunointervention strategy for the treatment of diffuse lung diseases.

Cytokines and chemokines are essential components for the pathophysiology of sarcoidosis. In the last decade, evidence has accumulated indicating that most of the events that lead to the alveolitis, granuloma formation and tissue injury are regulated by these mediators and their receptors. Recently, information on the possible pathogenetic role of cytokines has been translated into the development of potent cytokine antagonists which have proved to be powerful means of controlling disease activity in some inflammatory diseases.

Alveolar macrophage-T cell interactions during Th1-type sarcoid inflammation.

Sarcoidosis is an immunomediated, multisystem disorder of unknown cause(s) characterized by a heightened Th1 immune response that leads to an uncontrolled granuloma formation at sites of disease activity. The past few years have seen outstanding advances in the understanding of immunological and molecular events involved in the pathogenesis of this disease. The idea is that several cytokines and chemokines, which are secreted at sites of disease activity, participate in granuloma formation.

Cxcr3 and its ligand CXCL10 are expressed by inflammatory cells infiltrating lung allografts and mediate chemotaxis of T cells at sites of rejection.

The attraction of T lymphocytes into the pulmonary parenchyma represents an essential step in mechanisms ultimately leading to lung allograft rejection. In this study we evaluated whether IP-10 (CXCL10), a chemokine that is induced by interferon-gamma and stimulates the directional migration of activated T cells, plays a role in regulating the trafficking of effector T cells during lung allograft rejection episodes. Immunohistochemical examination showed that areas characterized by acute cellular rejection (grades 1 to 4) and active obliterative bronchiolitis (chronic rejection, Ca) were infiltrated by T cells expressing CXCR3, i.

Antiapoptotic effects of IL-15 on pulmonary Tc1 cells of patients with human immunodeficiency virus infection.

In the early phases of human immunodeficiency virus (HIV) disease a T-cell alveolitis sustained by cytotoxic T lymphocytes (CTL) with anti-HIV activity occurs in the lung. With the progression of HIV disease, pulmonary CTL become infected and their cytotoxic activity declines. To investigate the potential causes leading to this phenomenon, we evaluated T cells obtained from the bronchoalveolar lavage (BAL) of 18 HIV-infected patients with T-cell alveolitis.

CXC chemokines IP-10 and mig expression and direct migration of pulmonary CD8+/CXCR3+ T cells in the lungs of patients with HIV infection and T-cell alveolitis.

The recruitment of cytotoxic T lymphocytes (CTL) is considered to be the major tool for the clearance of HIV from the lower respiratory tract. In this study we evaluated the pathophysiologic role of two lymphotactic CXC chemokines (IP-10 and Mig) in the lung of HIV-infected patients. These chemokines stimulate the directional migration of activated T cells and interact with a specific receptor (CXC receptor 3, CXCR3).

B7 costimulatory molecules from malignant cells in patients with b-cell chronic lymphoproliferative disorders trigger t-cell proliferation.

Background: B7 family molecules are involved in T-B-cell communications after interaction with their ligands CD28 and CD152. They play a key role in costimulatory mechanisms and during antigen presentation by efficient antigen presenting cells. B7 molecules are usually absent or expressed at low intensity on B lymphocytes from healthy subjects.

Analysis of TNF-receptor and ligand superfamily molecules in patients with lymphoproliferative disease of granular lymphocytes.

In 21 patients with lymphoproliferative disease of granular lymphocytes (LDGL), we investigated the expression and the function of molecules belonging to TNF-receptor and TNF-ligand superfamilies (CD30/CD30L; CD40/CD40L; CD27/CD70; Fas [CD95]/FasL[CD95L]). Fourteen patients were characterized by a proliferation of granular lymphocytes (GLs) expressing the CD3(+)CD16(+) phenotype, whereas 7 cases showed the CD3(-)CD16(+) CD56 +/- phenotype. Our data show that both CD3(+) and CD3-GLs are preferentially equipped with CD30, CD40, CD40L, CD70, and CD95 antigens; this pattern is usually associated with the lack of CD27 and CD30L antigens expression.