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Mar Environ Res. 2002 Sep-Dec;54(3-5):565-8.
The Japanese medaka (Oryzias latipes) model: applicability for investigating the immunosuppressive effects of the aquatic pollutant benzo[a]pyrene (BaP).

Carlson EA, Li Y, Zelikoff JT.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo 10987, USA.

Despite the fact that BaP is a carcinogen, mammalian immunosuppressant, and ubiquitous aquatic pollutant, knowledge regarding the effects of BaP on the immune system of fish is still lacking. To begin to fill this gap, studies were conducted in medaka to examine the effects and mechanisms by which BaP exposure might alter host immunocompetence. Fish, exposed by IP injection of BaP (2-600 microg/g BW), were examined after 48 h for effects upon immune function and CYP1A expression/activity. Benzo[a]pyrene, at a concentration below that which increased levels of CYPIA expression/activity (2 microg BaP/g BW) suppressed lymphocyte proliferation. Concentrations of BaP at 20 and 200 microg/g BW. suppressed antibody-forming cell (AFC) numbers, superoxide production, and host resistance against bacteria. In contrast, exposure to the low affinity aryl hydrocarbon receptor (AhR) agonist, benzo[e]pyrene (BeP), neither induced CYP1A expression nor altered immune function. Given the lack of immunosuppressive effects produced by BeP, and the fact that exposure to the AhR antagonist (and CYP1A inhibitor) alpha-naphthoflavone (ANF) ameliorated the suppressive effects of BaP upon AFC numbers, the AhR pathway (including CYP1A-mediated production of reactive BaP metabolites) appears important in mediating BaP-induced immunotoxicity in fish, as in mammals. In the past, the medaka has proven a successful model for assessing carcinogenic agents. These studies have demonstrated its utility for also determining the immunosuppressive effects of an important aquatic contaminant.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12408618&dopt=Abstract

J Neurol Sci. 2002 Dec 15;205(1):47-50.
An assessment of the association between IL-2 gene polymorphisms and Japanese patients with multiple sclerosis.

Kikuchi S, Niino M, Fukazawa T, Yabe I, Tashiro K.

Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, 060-8638 Sapporo, Japan.

Interleukin-2 (IL-2) is a cytokine intimately involved with both the function and regulation of the immune system. Genetic analysis of experimental autoimmune encephalomyelitis (EAE) provides strong evidence supporting the candidacy of IL-2 as a susceptibility gene. We investigated the association of two single nucleotide polymorphisms (SNPs) at position -384 in the promoter region and +114 in the first exon of the IL-2 gene through a case-control study involving 113 Japanese patients with multiple sclerosis (MS) and 118 healthy controls. Our results showed no significant differences in the distribution of the two polymorphisms between MS patients and controls. Furthermore, no association was observed between IL-2 gene polymorphisms and clinical characteristics, such as clinical course and age at disease onset. Together, our findings suggest that IL-2 gene polymorphisms do not influence the susceptibility to MS or the clinical characteristics of MS in Japanese patients.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12409183&dopt=Abstract

FASEB J. 2002 Nov;16(13):1749-54.
Prevention of spontaneous mammary adenocarcinoma in HER-2/neu transgenic mice by foreign DNA.

Sfondrini L, Besusso D, Rumio C, Rodolfo M, Menard S, Balsari A.

Molecular Targeting Unit, Melanoma Genetics Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy.

Unmethylated CpG-oligodeoxynucleotides (CpG-ODNs) are recognized as a 'danger signal' and are potent immunostimulators. To test whether tumors might be prevented by maintaining the innate immune system on continuous alert, proto-neu transgenic female mice, which develop spontaneous mammary tumors, were systemically treated with CpG-ODNs at 10-day intervals. Tumor incidence and number of tumors/mouse were significantly lower in treated mice compared with the control group. Moreover, CpG-ODN systemic treatment significantly reduced lung metastases induced by intravenous inoculation of N202.1A cells derived from a spontaneous mammary carcinoma. Growth of established tumors was modestly inhibited after CpG-ODN systemic treatment but strongly on peritumoral application. Our data indicate that systemic repeated injection of CpG-ODN to maintain the innate immune system on continuous alert prevents the onset of genetically determined tumors and confers tumor protection when the tumor load is low.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12409317&dopt=Abstract

J Clin Microbiol. 2002 Nov;40(11):4131-7.
Detection of antibodies directed against human herpesvirus 6 U94/REP in sera of patients affected by multiple sclerosis.

Caselli E, Boni M, Bracci A, Rotola A, Cermelli C, Castellazzi M, Di Luca D, Cassai E.

Section of Microbiology, Department of Experimental and Diagnostic Medicine. Section of Neurology, Department of Medical Surgical, Communication and Behavioral Sciences, University of Ferrara, Ferrara, Italy.

The association between human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) is controversial. In fact, it is difficult to establish a causative role of HHV-6, due to the high prevalence of latently infected individuals in the healthy population. Therefore, the presence of virus sequences in tissue biopsy does not support a viral role, and serological assays do not show significant differences between MS patients and control populations. The only viral gene expressed during latency is U94/rep. Therefore, we have developed a serological assay for the detection of antibodies specifically directed against U94/REP protein. Different populations were analyzed by enzyme-linked immunosorbent assay, including healthy controls, MS patients, and subjects with diseases unrelated to HHV-6 infection, including other neurological diseases. The results show statistically significant differences (P > 0.01) between MS patients and control groups, both in antibody prevalence (87 and 43.9%, respectively) and in geometric mean titer (1:515 and 1:190, respectively). The detection of antibodies specific for HHV-6 U94/REP shows that the immune system is exposed to this antigen during natural infection. The higher prevalence and higher titers of antibodies to U94/REP suggest that MS patients and control groups might experience different exposures to HHV-6.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12409386&dopt=Abstract

AIDS. 2002 Nov 8;16(16):2129-35.
Rapid reconstitution of humoral immunity against cytomegalovirus but not HIV following highly active antiretroviral therapy.

Deayton JR, Sabin CA, Britt WB, Jones IM, Wilson P, Johnson MA, Griffiths PD, Emery VC.

Department of Virology, Royal Free Hampstead NHS Trust and Royal Free and University College School of Medicine, London, UK.

OBJECTIVE: To determine the kinetics of reduction in human cytomegalovirus (HCMV) load and specific anti-glycoprotein B (gB) immune responses in patients with concurrent HCMV DNAaemia following the initiation of highly active antiretroviral therapy (HAART). DESIGN: Sequential analysis of eleven patients with HCMV DNAaemia who received HAART and eleven control patients with HCMV DNAaemia. METHODS: HCMV load was measured by quantitative competitive polymerase chain reaction and anti-gB, anti-HIV Env and Gag responses by an end-point dilution immunofluorescence assay using recombinant antigens expressed in insect cells. Estimates of the efficacy of the reconstituting immune system at controlling HCMV replication were based on previous dynamic models. RESULTS: In patients initiating HAART, HCMV DNA levels in blood declined rapidly, with a median half-life of 5.2 days, consistent with an efficacy of the reconstituting immune system at inhibiting HCMV replication of 52.8-85% (median, 61%). Commensurate with this decrease, a significant increase in anti-gB titres was observed in the post-HAART period (corresponding to an average fourfold increase in titre by 1 month rising to an eightfold increase at month 3; = 0.01). No changes in titre were observed in the control group or for anti-HIV Gag antibody levels, while anti-HIV Env antibody levels decreased after HAART. CONCLUSIONS: In patients with HCMV DNAaemia, reconstitution of humoral immunity to HCMV gB occurs rapidly following the initiation of HAART. These changes contrast with the patterns observed for anti-HIV humoral immune responses.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12409733&dopt=Abstract

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