Consumption of fruit, vegetables, and other food groups and the risk of nasopharyngeal carcinoma

Purpose

The role of dietary habits in the etiology of nasopharyngeal carcinoma (NPC) has been extensively investigated in high-incidence areas, but evidence is scanty in low-incidence populations. This study aimed to investigate the relationship between NPC risk and a wide range of food groups in the Italian population.

Methods

We conducted a hospital-based case–control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity, aged 18–76 years. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression, adjusting for socio-demographic characteristics, tobacco smoking, alcohol drinking, and energy intake.

Results

Elevated vegetable consumption was inversely related to NPC risk (OR for highest vs. lower quartile = 0.51; 95 % CI 0.29–0.90). The association was particularly strong for yellow- or red-pigmented vegetables (OR = 0.31; 95 % CI 0.18–0.54), and this effect was stronger among never smokers (OR = 0.18; 95 % CI 0.06–0.55) than among ever smokers (OR = 0.37; 95 % CI 0.19–0.71). Increased NPC risk emerged for elevated eggs consumption (OR = 2.50; 95 % CI 1.44–4.32; p-trend <0.01). No significant associations emerged between NPC risk and consumption of cereals, meat, fish, dairy products, and sweets.

Conclusions

The study findings show that, also in low-risk populations, vegetable consumption is a protective factor against NPC. The stronger effect for yellow- or red-pigmented vegetables is in agreement with the inverse association reported for carotenoids intake.     

nNOS is involved in behavioral thermoregulation of newborn rats during hypoxia

The present study was undertaken to investigate the role of nitric oxide (NO) pathway in the behavioral thermoregulation of newborn rats in cold and hypoxia. We predicted that injection of L-NAME (non-selective NO synthase (NOS) inhibitor) and SMTC (neuronal NOS (nNOS) inhibitor) would restore the huddling behavior and eliminate the reduction of Tb caused by hypoxia. Experiments were performed on Wistar rat pups of 7-9 days old. We measured Tb and analyzed the huddling behavior by means of the calculation of the total surface area occupied by 5 pups and the number of single pups grouped in the center of a chamber at 20 degrees C, before and after L-NAME, SMTC or their respective vehicles (D-NAME and saline) s.c. injections. Subsequently, the pups were exposed to hypoxia (10% O(2)) during 30 min, whereas control animals were kept under normoxia. The experiments were monitored by a digital camera. All animals were hypothermic when exposed to 20 degrees C. There was no significant difference in Tb, total area and number of single pups in normoxia after treatments. During hypoxia, the drop in Tb was higher in control groups, and this effect was attenuated by L-NAME and SMTC injections. Hypoxia increased the area occupied by the pups in saline, D-NAME and L-NAME groups, while SMTC attenuated this response. The data indicate that NO pathway is involved in the inhibition of huddling behavior and in the reduction of Tb caused by hypoxia, but plays no role during normoxia. Furthermore, NO seems to arise from the nNOS isoform.     

Real-time RT-PCR for detection of Raspberry bushy dwarf virus, Raspberry leaf mottle virus and characterizing synergistic interactions in mixed infections

Two TaqMan-based real-time One-Step RT-PCR assays were developed for the rapid and efficient detection of Raspberry bushy dwarf virus (RBDV) and Raspberry leaf mottle virus (RLMV), two of the most common raspberry viruses in North America and Europe. The primers and probes were designed from conserved fragments of the polymerase region of each virus and were effective for the detection of different isolates tested in this study. The RBDV assay amplified a 94 bp amplicon and was able to detect as few as 30 viral copies. Whereas the RLMV assay amplified a 180 bp amplicon and detected as few as 300 viral copies from plant and aphid RNA extracts. Both assays were significantly more sensitive than their corresponding conventional RT-PCR methods. The sensitivity of the RLMV assay was also tested on single aphids after a fixed acquisition access period (AAP). In addition, the assays revealed a novel synergistic interaction between the two viruses, where the concentration of RBDV was enhanced ∼400-fold when it occurred in combination with RLMV compared to its concentration in single infections. The significance of this finding and the importance of the development of real-time RT-PCR assays for the detection of RBDV and RLMV are discussed.     

Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis

CD8 T lymphocytes are important effectors in protective immunity against Mycobacterium tuberculosis. We recently characterized the detour pathway of CD8 T cell activation in tuberculosis mediated by apoptotic vesicles from infected cells that transport mycobacterial antigens to dendritic cells (DCs). Here we demonstrate that apoptotic vesicles from mycobacteria-infected macrophages stimulate CD8 T cells in vivo. Homing of DCs to draining lymph nodes was critically required for effective crosspriming. Subsequent fate of vesicle-associated antigens in recipient DCs was characterized by endosomal mechanisms predominating over proteasomal processing. In addition, vesicle processing depended on the presence of saposins to disintegrate apoptotic membranes. Apoptotic vesicles displayed potent adjuvant activity by stimulating through Toll-like receptors (TLR). Ultimately, vaccination with vesicles from infected cells induced protection against M. tuberculosis infection. Taken together, we propose the detour pathway to represent a genuine immunological mechanism mediating crosspriming of CD8 T cells in vivo and protection against tuberculosis.     

Therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues SIV‐specific CD4+ T‐cell‐dependent natural killer cell effector responses in chronically infected rhesus macaques

Natural killer (NK) cells are essential components of the immune system, and due to their rapid response potential, can have a great impact during early anti‐viral immune responses. We have previously shown that interleukin‐2‐dependent NK and CD4⁺ T‐cell co‐operative immune responses exist in long‐term simian immunodeficiency virus (SIV) ‐infected controlling macaques and can be rescued in SIV‐infected non‐controlling macaques by a short course of antiretroviral therapy (ART). Given that co‐operative responses may play an important role in disease prevention and therapeutic treatment, in the present study we sought to determine if these responses can be enhanced in chronically SIV‐infected macaques by vaccination with a single‐dose of envelope protein given during ART. To this end, we treated 14 chronically SIV‐infected macaques with ART for 11 weeks and gave 10 of these macaques a single intramuscular dose of SIV gp120 at week 9 of treatment. ART significantly decreased plasma and mucosal viral loads, increased the numbers of circulating CD4⁺ T cells in all macaques, and increased T‐cell‐dependent envelope‐ and gag‐specific interferon‐γ and tumour necrosis factor‐α production by circulatory CD56⁺ NK cells. The therapeutic envelope immunization resulted in higher envelope‐specific responses compared with those in macaques that received ART only. Functional T‐cell responses restored by ART and therapeutic Env immunization were correlated with transiently reduced plasma viraemia levels following ART release. Collectively our results indicate that SIV‐specific T‐cell‐dependent NK cell responses can be efficiently rescued by ART in chronically SIV‐infected macaques and that therapeutic immunization may be beneficial in previously vaccinated individuals.     

Gorgan (Turkmen in Iran) HLA genetics: transplantation,pharmacogenomics and anthropology

HLA class I and II alleles have been studied in a population from Gorgan (North East Iranian city bordering Turkmenistan). This population is composed of mainly Turkmen who speak Oghuz Turkish language. Comparison of Gorgan people HLA profile has been carried out with about 7984 HLA chromosomes from other worldwide populations; extended haplotypes and three dimension genetic distances have been calculated by using neighbor-joining and correspondence relatedness analyses. Most frequent extended HLA haplotypes show a Siberian/Mediterranean admixture and closest populations are Chuvashians (North Caspian Sea, Russia) and other geographically close populations like Siberian Mansi, Buryats and other Iranians. New extended HLA haplotypes have been found, such as: A*31:01-B*35:01-DRB1*15:01-DQB1*03:01, A*01:01-B*35:01-DRB1*03:01-DQB1*02:01. Relationships of Turkmen with Kurgan (Gorgan) archaeological mounds, Scythians and Sarmatians are discussed. This study is also useful for a future transplantation Gorgan waiting list, Gorgan HLA and disease epidemiology and HLA pharmacogenomics.     

A Replicating Adenovirus Capsid Display Recombinant Elicits Antibodies against Plasmodium falciparum Sporozoites in Aotus nancymaae Monkeys

Decades of success with live adenovirus vaccines suggest that replication-competent recombinant adenoviruses (rAds) could serve as effective vectors for immunization against other pathogens. To explore the potential of a live rAd vaccine against malaria, we prepared a viable adenovirus 5 (Ad5) recombinant that displays a B-cell epitope from the circumsporozoite protein (CSP) of Plasmodium falciparum on the virion surface. The recombinant induced P. falciparum sporozoite-neutralizing antibodies in mice. Human adenoviruses do not replicate in mice. Therefore, to examine immunogenicity in a system in which, as in humans, the recombinant replicates, we constructed a similar recombinant in an adenovirus mutant that replicates in monkey cells and immunized four Aotus nancymaae monkeys. The recombinant replicated in the monkeys after intratracheal instillation, the first demonstration of replication of human adenoviruses in New World monkeys. Immunization elicited antibodies both to the Plasmodium epitope and the Ad5 vector. Antibodies from all four monkeys recognized CSP on intact parasites, and plasma from one monkey neutralized sporozoites in vitro and conferred partial protection against P. falciparum sporozoite infection after passive transfer to mice. Prior enteric inoculation of two animals with antigenically wild-type adenovirus primed a response to the subsequent intratracheal inoculation, suggesting a route to optimizing performance. A vaccine is not yet available against P. falciparum, which induces the deadliest form of malaria and kills approximately one million children each year. The live capsid display recombinant described here may constitute an early step in a critically needed novel approach to malaria immunization.     

Protective and Pathological Functions of CD8+ T Cells in Leishmania braziliensis Infection

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a strong Th1 response that leads to skin lesion development. In areas where L. braziliensis transmission is endemic, up to 15% of healthy subjects have tested positive for delayed-type hypersensitivity to soluble leishmania antigen (SLA) and are considered to have subclinical (SC) infection. SC subjects produce less gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) than do CL patients, but they are able to control the infection. The aim of this study was to characterized the role of CD8⁺ T cells in SC infection and in CL. Peripheral blood mononuclear cells (PBMC) were stimulated with SLA to determine the frequencies of CD4⁺ IFN-γ⁺ and CD8⁺ IFN-γ⁺ T cells. Monocytes from PBMC were infected with L. braziliensis and cocultured with CD8⁺ T cells, and the frequencies of infected monocytes and levels of cytotoxicity markers, target cell apoptosis, and granzyme B were determined. The frequency of CD8⁺ IFN-γ⁺ cells after SLA stimulation was higher for SC individuals than for CL patients. The frequency of infected monocytes in SC cells was lower than that in CL cells. CL CD8⁺ T cells induced more apoptosis of infected monocytes than did SC CD8⁺ T cells. Granzyme B production in CD8⁺ T cells was higher in CL than in SC cells. While the use of a granzyme B inhibitor decreased the number of apoptotic cells in the CL group, the use of z-VAD-FMK had no effect on the frequency of these cells. These results suggest that CL CD8⁺ T cells are more cytotoxic and may be involved in pathology.