A review on aflatoxin contamination and its implications in the developing world: a sub-Saharan African perspective.

Mycotoxins contamination in some agricultural food commodities seriously impact human and animal health and reduce the commercial value of crops. Mycotoxins are toxic secondary metabolites produced by fungi that contaminate agricultural commodities pre- or postharvest. Africa is one of the continents where environmental, agricultural and storage conditions of food commodities are conducive of Aspergillus fungi infection and aflatoxin biosynthesis. This paper reviews the commodity-wise aetiology and contamination process of aflatoxins and evaluates the potential risk of exposure from common African foods. Possible ways of reducing risk for fungal infection and aflatoxin development that are relevant to the African context. The presented database would be useful as benchmark information for development and prioritization of future research. There is need for more investigations on food quality and safety by making available advanced advanced equipments and analytical methods as well as surveillance and awareness creation in the region.

Mycoflora and occurrence of aflatoxin in dried vegetables in Benin, Mali and Togo, West Africa.

Fungal infection and aflatoxin contamination was evaluated on 180 samples of dried vegetables such as okra, hot chilli, tomato, melon seeds, onion and baobab leaves from Benin, Togo and Mali collected in September to October 2006. These products are dried to preserve them for lean periods and decrease their perishability. Fungal contamination was evaluated after plating on selective media with a total of 561 fungal isolates identified, ranging from 18 in tomato and 218 in baobab leaves. Baobab leaves, followed by hot chilli and okra showed high incidence of fungal contamination compared to the other dried vegetables, while shelled melon seeds, onion leaves and dried tomato had lower levels of fungal contamination. Species of Aspergillus were dominant on all marketed dried vegetables irrespective of country. Mycotoxin assessment by Reversed-Phase High Performance Liquid Chromatography showed that only okra and hot chilli were naturally contaminated with aflatoxin B(1) and aflatoxin B(2), at concentrations of 6.0 microg/kg on okra and 3.2 microg/kg on hot pepper. This is the first time that mycotoxigenic fungi and resultant toxins were found on dried vegetable products sampled from African markets. Previous reports have mostly highlighted the risk of mycotoxin exposure from staple crops in Africa, but such risks now need to be evaluated for other products such as dried vegetables.

Mycoflora and natural occurrence of aflatoxins and fumonisin B1 in cassava and yam chips from Benin, West Africa.

The presence of fungi, aflatoxins and fumonisin B1 in cassava and yam chips (during 28 processing and storage) were evaluated during two consecutive seasons in two agroecological zones of Benin (Northern Guinea Savannah, NGS and Sudan Savannah, SS). The Benin samples were assessed for moisture content, fungal infestation and total aflatoxin and fumonisin B1 contamination. During the two seasons, samples collected from the NGS, had moisture contents ranging from 10.0 to 14.7% in cassava chips and from 11.4 to 15.3% in yam chips. In samples from the SS, moisture content ranged from 10.1 to 14.5% and 11.1 to 14.5% in cassava and yam chips, respectively. A. flavus was the predominant fungal species. The maximum cfu/g in cassava and yam chips was 8950 and 6030, respectively. Other fungal species isolated included P. chrysogenum, M. piriformis, Phoma sorghina, F. verticillioides, R. oryzae and Nigrospora oryzae. High performance liquid chromatography analysis of both cassava and yam chips showed no contamination by either aflatoxins or fumonisin B1.

Infestation and population dynamics of insects on stored cassava and yams chips in Benin, West Africa.

Natural insect infestation in cassava (Manihot esculenta Crantz subspecies esculenta) and yam (Dioscorea spp.) chips was evaluated during two consecutive storage seasons (2003-2004 and 2004-2005) in two agroecological zones of Benin (Northern Guinea Savanna [NGS] and Sudan Savanna [SS]). The insects infesting chips were collected, identified, and counted, they included Prostephanus truncatus (Horn) (Coleoptera: Bostrychidae), Cathartus quadricollis (Guerin) (Coleoptera: Silvanidae), Carpophilus dimidiatus (F.) (Coleoptera: Nitidulidae), Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), and Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae). P. truncatus and C. quadricollis were observed with a higher prevalence on cassava than on yam chips. During both seasons after 3 mo of storage, all (100%) cassava chip samples were infested with P. truncatus and C. quadricollis in both agroecological zones, whereas yam chips only showed lower infestation rates of 59.5 and 19.1% for P. truncatus and C. quadricollis, respectively, at the end of storage in 2003-2004. During the 2004-2005 season after 3 mo of storage infestation rate in yam chips was 66 and 24% in NGS and 100 and 0% in SS for P. truncatus and C. quadricollis, respectively, showing that insect infestation levels vary significantly with commodity, year, and fluctuate during the storage season.

Public information campaign on aflatoxin contamination of maize grains in market stores in Benin, Ghana and Togo.

Rotary International with the International Institute of Tropical Agriculture (IITA) conducted an information campaign from 2000 to 2004 to increase public awareness of aflatoxin in Benin, Ghana and Togo. Key informant interviews with 2416 respondents showed poor baseline knowledge of aflatoxin and its health risks. The campaign included monitoring of aflatoxin contamination in maize grains from market stores in 38 cities and towns. Aflatoxin concentration in contaminated samples ranged from 24 to 117.5 ng g(-1) in Benin, from 0.4 to 490.6 ng g(-1) in Ghana, and from 0.7 to 108.8 ng g(-1) in Togo. The campaign significantly increased public awareness that populations were exposed to high levels of aflatoxin. The number of maize traders who were informed about the toxin increased 10.3 and 3.2 times in Togo and Benin, respectively; at least 33% more traders believed the information in each of Benin and Togo; 11.4 and 28.4% more consumers sorted out and discarded bad grains in Benin and Ghana, respectively. This paper concludes that sustained public education can help reduce aflatoxin contamination.

Impact of mechanical shelling and dehulling on Fusarium infection and fumonisin contamination in maize.

Mechanical shelling and dehulling methods were tested to evaluate their impact on Fusarium infection and fumonisin contamination in maize. All shelling methods which were tested were found to damage the grains. The IITA sheller caused the highest level (up to 3.5%) of damage. Fusarium populations were higher on damaged grains, the highest being recorded from grains damaged by the IITA sheller (2,533.3 cfu g(-1)). Fumonisin levels were higher in damaged grains, the highest being in maize shelled with the IITA sheller (2.2 mg kg(-1)). Fumonisin levels were positively and significantly correlated with the percentage of damage caused by the shelling methods, and with the number of Fusarium colonies in maize. Mechanical dehulling methods significantly reduced fumonisin levels in maize, resulting in a mean reduction of 62% for Mini-PRL, 65% for Engelberg, and 57% for the attrition disc mill. It is important for farmers to choose appropriate shelling methods to reduce mycotoxin contamination. Dehulling should be widely promoted for the reduction of mycotoxins in maize.

Influence of substrate binding on the mechanical stability of mouse dihydrofolate reductase.

We investigated the effect of substrate binding on the mechanical stability of mouse dihydrofolate reductase using single-molecule force spectroscopy by atomic force microscopy. We find that under mechanical forces dihydrofolate reductase unfolds via a metastable intermediate with lifetimes on the millisecond timescale. Based on the measured length increase of approximately 22 nm we suggest a structure for this intermediate with intact substrate binding sites. In the presence of the substrate analog methotrexate and the cofactor NADPH lifetimes of this intermediate are increased by up to a factor of two. Comparing mechanical and thermodynamic stabilization effects of substrate binding suggests mechanical stability is dominated by local interactions within the protein structure. These experiments demonstrate that protein mechanics can be used to probe the substrate binding status of an enzyme.

Dietary exposure to aflatoxin from maize and groundnut in young children from Benin and Togo, West Africa.

Aflatoxins are a family of fungal toxins that are carcinogenic to man and cause immunosuppression, cancer and growth reduction in animals. We conducted a cross-sectional study among 480 children (age 9 months to 5 years) across 4 agro-ecological zones (SS, NGS, SGS and CS) in Benin and Togo to identify the effect of aflatoxin exposure on child growth and assess the pattern of exposure. Prior reports on this study [Gong, Y.Y.,Cardwell, K., Hounsa, A., Egal, S., Turner, Hall, A.J., Wild, C.P., 2002. Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: cross sectional study. British Medical Journal 325, 20-21, Gong, Y.Y., Egal, S., Hounsa, A., Turner, P.C., Hall, A.J., Cardwell, K., Wild, C.P., 2003. Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: the critical role of weaning and weaning foods. International Journal of Epidemiology, 32, 556-562] showed that aflatoxin exposure among these children is widespread (99%) and that growth faltering is associated with high blood aflatoxin-albumin adducts (AF-alb adducts), a measure of recent past exposure. The present report demonstrates that consumption of maize is an important source of aflatoxin exposure for the survey population. Higher AF-alb adducts were correlated with higher A. flavus (CFU) infestation of maize (p=0.006), higher aflatoxin contamination (ppb) of maize (p<0.0001) and higher consumption frequencies of maize (p=0.053). The likelihood of aflatoxin exposure from maize was particularly high in agro-ecological zones where the frequency of maize consumption (SGS and CS), the presence of aflatoxin in maize (SGS) or the presence of A. flavus on maize (NGS and SGS) was relatively high. Socio-economic background did not affect the presence of A. flavus and aflatoxin in maize, but better maternal education was associated with lower frequencies of maize consumption among children from the northernmost agro-ecological zone (SS) (p=0.001). The impact of groundnut consumption on aflatoxin exposure was limited in this population. High AF-alb adduct levels were correlated with high prevalence of A. flavus and aflatoxin in groundnut, but significance was weak after adjustment for weaning status, agro-ecological zone and maternal socio-economic status (resp. p=0.091 and p=0.083). Ingestion of A. flavus and aflatoxin was high in certain agro-ecological zones (SS and SGS) and among the higher socio-economic strata due to higher frequencies of groundnut consumption. Contamination of groundnuts was similar across socio-economic and agro-ecological boundaries. In conclusion, dietary exposure to aflatoxin from groundnut was less than from maize in young children from Benin and Togo. Intervention strategies that aim to reduce dietary exposure in this population need to focus on maize consumption in particular, but they should not ignore consumption of groundnuts.

Natural occurrence of Fusarium and subsequent fumonisin contamination in preharvest and stored maize in Benin, West Africa.

The natural occurrence of Fusarium and fumonisin contamination was evaluated from 1999 to 2003 in both preharvest and stored maize produced by small-scale farmers in four agroecological zones of Benin. Mycological analyses revealed a predominance of both Fusarium and Aspergillus in maize samples compared to other genera. The two Fusarium species most commonly isolated from maize were Fusarium verticillioides (68%) and Fusarium proliferatum (31%). Atypical isolates of F. verticillioides with some characteristics of Fusarium andiyazi but apparently closer to F. verticillioides, because the isolates were all high fumonisin producers, were also found only on preharvest maize. Study of F. verticillioides strains showed the presence of extremely high fumonisin producers in Benin with total fumonisin levels ranging from 8240 to 16,690 mg/kg. Apart from 2002-2003, Fusarium occurrence was not significantly different from one zone to another, although a slight decrease was observed from south, humid, to north, drier. Fusarium occurrence varied somewhat from one season to another. It significantly decreased over the 6 months of storage. Widespread fumonisin occurrence in maize was observed. Most of the maize samples collected were found positive for fumonisin with levels ranging from not detected to 12 mg/kg in 1999-2000, 6.7 mg/kg in 2000-2001 and 6.1 mg/kg in 2002-2003. Fumonisin levels in maize were found to be significantly higher in the two southern zones during all the surveys. The highest mean total fumonisin level was detected in 1999-2000 in maize samples from the southern Guinea Savannah (SGS) (12 mg/kg), whereas in both 2000-2001 and 2002-2003, it was in samples from the forest mosaic savannah (FMS) (6.7 and 6.1 mg/kg, respectively). Fumonisin levels varied from one season to another and, throughout the storage time, showing a decreasing trend in each zone. However, this decrease was not significant every season. An increasing trend was observed during some seasons in the SGS and northern Guinea Savannah (NGS) zones. The results of this study emphasise that farmers and consumers, not only in Benin but also in other West African countries, should be alerted to the danger of fumonisin contamination in maize.

Fate of aflatoxins and fumonisins during the processing of maize into food products in Benin.

The fate of aflatoxins and fumonisins, two mycotoxins that cooccur in maize, was studied through the traditional processing of naturally contaminated maize in mawe, makume, ogi, akassa, and owo, maize-based foods common in Benin, West Africa. Levels of total aflatoxin and fumonisin were measured at the main unit operations of processing, and the unit operations that induce significant reduction of mycotoxin level were identified. Overall reduction of mycotoxin level was more significant during the preparation of makume (93% reduction of aflatoxins, 87% reduction of fumonisins) and akassa (92% reduction of aflatoxins, 50% reduction of fumonisins) than that of owo (40% reduction of aflatoxins, 48% reduction of fumonisins). Sorting, winnowing, washing, crushing combined with dehulling of maize grains were the unit operations that appeared very effective in achieving significant mycotoxin removal. Aflatoxins and fumonisins were significantly recovered in discarded mouldy and damaged grains and in washing water. Fermentation and cooking showed little effect. During the preparation of ogi and akassa, reduction of fumonisin levels measured in food matrix was lower (50%) compared to mawe and makume, probably due to significant fumonisin release in ogi supernatant. Consequently, the use of ogi supernatant for preparing beverages or traditional herbal medicines could be harmful as it is likely to be contaminated with mycotoxin from the raw maize.

Catalytic activity of caspase-3 is required for its degradation: stabilization of the active complex by synthetic inhibitors.

The activation of caspase-3 represents a critical step in the pathways leading to the biochemical and morphological changes that underlie apoptosis. Upon induction of apoptosis, the large (p17) and small (p12) subunits, comprising active caspase-3, are generated via proteolytic processing of a latent proenzyme dimer. Two copies of each individual subunit are generated to form an active heterotetramer. The tetrameric form of caspase-3 cleaves specific protein substrates within the cell, thereby producing the apoptotic phenotype. In contrast to the proenzyme, once activated in HeLa cells, caspase-3 is difficult to detect due to its rapid degradation. Interestingly, however, enzyme stability and therefore detection of active caspase-3 by immunoblot analysis can be restored by treatment of cells with a peptide-based caspase-3 selective inhibitor, suggesting that the active form can be stabilized through protein-inhibitor interaction. The heteromeric active enzyme complex is necessary for its stabilization by inhibitors, as expression of the large subunit alone is not stabilized by the presence of inhibitors. Our results show for the first time, that synthetic caspase inhibitors not only block caspase activity, but may also increase the stability of otherwise rapidly degraded mature caspase complexes. Consistent with these findings, experiments with a catalytically inactive mutant of caspase-3 show that rapid turnover is dependent on the activity of the mature enzyme. Furthermore, turnover of otherwise stable active site mutants of capase-3 is rescued by the presence of the active enzyme suggesting that turnover can be mediated in trans.

Substrate cleavage by caspases generates protein fragments with Smac/Diablo-like activities.

Smac/Diablo and HtrA2/Omi promote apoptosis by binding to and antagonizing IAP proteins, including the 'X chromosome-linked inhibitor of apoptosis' (XIAP). Here we show that caspase-mediated proteolysis of a limited subset of cell death substrates exposes functional Smac/Diablo-like N-termini after cleavage, which are able to bind to and antagonize XIAP. We propose that this mechanism may establish a feedforward sensitization of the apoptotic pathway and contribute to the functional redundancy of IAP antagonism. In addition, this may be particularly relevant in Alzheimer's disease since the caspase-generated C31 peptide, an established cytotoxin, acquires Smac/Diablo-like properties after apoptotic processing.

Mechanistic aspects of the de-novo synthesis of PCDD/PCDF on model mixtures and MSWI fly ashes using amorphous 12C- and 13C-labeled carbon.

The formation of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) from amorphous 12C- and 13C-labeled carbon was studied on model mixtures and real fly ashes. PCDD/F can either be formed directly (de-novo) from carbon already present in fly ash or step-by-step via condensation of two aromatic rings. Using model mixtures containing 12C- and 13C-labeled carbon in various ratios we observed the formation of the following compound classes: 12C6-PCPh, -PCBz, 13C6-PCPh, -PCBz, 12C12-PCDD/ F, 13C12-PCDD/F, and 12C6 13C6-PCDD/F. By examining the fraction of the mixed PCDD/F (one of the two aromatic ring is composed solely of 12C-atoms while the other contains only 13C-atoms) in the total concentration of PCDD/F, conclusions on the formation of these three ring structures are possible. From the experimental results, it can be concluded that both reaction mechanisms are operative in the formation of PCDD/F from carbon. On fly ashes approximately half of the total amount of PCDD is formed via condensation of de-novo created C6-precursors e.g. chlorophenols, while the remainder is directly released (de-novo) from the carbon i.e., formed from a related C12-structure. However, the condensation of intermediate aromatic C6-precursors is of minor importance in the formation of PCDF. With increasing temperature the relative amount of the 12C6 13C6-PCDD formed by condensation decreases due to the faster evaporation of chlorophenols. At a constant reaction temperature, the ratio of both reaction pathways is hardly influenced by reaction time. In experiments with fly ashes doped with 13C-labeled carbon, this carbon isotope shows a similar reactivity as the native carbon present on the fly ash. Thus, the used amorphous carbons are suitable models for this investigation.

Regional distribution of ornithine decarboxylase activity and polyamine levels in experimental cat brain tumors.

Biosynthesis of the polyamines putrescine, spermidine, and spermine, and activation of the first key enzyme ornithine decarboxylase (ODC) are closely associated with cellular proliferation. In the present study, the distribution of ODC activity and polyamine levels was investigated for the first time regionally in experimental brain tumors of the cat. Brain tumors were produced by stereotactic xenotransplantation of rat glioma cells. Twenty days after implantation, the brains were frozen in situ, cut into slices, and cryostat sections and tissue samples were taken to determine ODC activity and polyamine levels biochemically. The quantified data were color-coded to present the regional distribution of ODC activity and polyamine levels in the respective section. ODC activity significantly increased in some areas within the tumor, whereas peritumoral tissue showed no difference to the non-tumoral, contralateral hemisphere. This increase turned out in parallel to a high number of mitoses in the same tumor parts (r=0.861). Putrescine levels increased both, in the whole tumor and in the peritumoral edema. Regional differences in putrescine content did not correlate with solid and proliferative parts of the tumor. Spermidine and spermine levels were only slightly increased in some parts of the tumor. Thus, these experiments show the close correlation of a high mitotic rate and activation of ODC within experimental gliomas and underline the relevance of ODC as a biochemical marker of proliferation in brain tumors.

Mba1, a novel component of the mitochondrial protein export machinery of the yeast Saccharomyces cerevisiae.

The biogenesis of mitochondria requires the integration of many proteins into the inner membrane from the matrix side. The inner membrane protein Oxa1 plays an important role in this process. We identified Mba1 as a second mitochondrial component that is required for efficient protein insertion. Like Oxa1, Mba1 specifically interacts both with mitochondrial translation products and with conservatively sorted, nuclear-encoded proteins during their integration into the inner membrane. Oxa1 and Mba1 overlap in function and substrate specificity, but both can act independently of each other. We conclude that Mba1 is part of the mitochondrial protein export machinery and represents the first component of a novel Oxa1-independent insertion pathway into the mitochondrial inner membrane.

Oxa1p acts as a general membrane insertion machinery for proteins encoded by mitochondrial DNA.

Oxa1p is a member of the conserved Oxa1/YidC/Alb3 protein family involved in the membrane insertion of proteins. Oxa1p has been shown previously to directly facilitate the export of the N-terminal domains of membrane proteins across the inner membrane to the intermembrane space of mitochondria. Here we report on a general role of Oxa1p in the membrane insertion of proteins. (i) The function of Oxa1p is not limited to the insertion of membrane proteins that undergo N-terminal tail export; rather, it also extends to the insertion of other polytopic proteins such as the mitochondrially encoded Cox1p and Cox3p proteins. These are proteins whose N-termini are retained in the mitochondrial matrix. (ii) Oxa1p interacts directly with these substrates prior to completion of their synthesis. (iii) The interaction of Oxa1p with its substrates is particularly strong when nascent polypeptide chains are inserted into the inner membrane, suggesting a direct function of Oxa1p in co-translational insertion from the matrix. Taken together, we conclude that the Oxa1 complex represents a general membrane protein insertion machinery in the inner membrane of mitochondria.

Dioxins from thermal and metallurgical processes: recent studies for the iron and steel industry.

In thermal metallurgical processes such as iron ore sintering and metal smelting operations, large flows of off-gases are generated. Mainly due to residue recycling in such processes, chlorine and volatile organics are always present in the feed. As a consequence of "de novo" formation, the off-gases from such processes typically contain dioxins in the range 0.3-30 ng I-TEQ/Nm3. So far there are only very few studies about the mechanisms of dioxin formation and destruction in these metallurgical processes. In an European Union (EU) research project "Minimization of dioxins in thermal industrial processes: mechanisms, monitoring and abatement (MINIDIP)", integrated iron and steel plant has been selected as one of the industrial sectors for further investigation. A large number of particulate samples (feed, belt siftings, electrofilter) were collected from the iron ore sintering installations from various steel plants and analyzed for their organochlorocompound contents. Measurable amounts of PCDD/F, PCBz, PCB were found for all samples. The various parameters influencing their de novo synthesis activity were also evaluated in laboratory experiments, and such activity was found to be moderate for samples from the ore sinter belt, but extremely high for some ESP dusts. Fine dust is active in a wide range of temperatures starting at 200 degrees C and declining above 450 degrees C; the optimal temperature for de novo synthesis was found to be around 350 degrees C; some inhibitors, such as triethanolamine, may reduce de novo activity by 50%, and lowering the O2 concentration in the gas stream leads to a much lower amount of PCDD/F formation. On the basis of their relative mass, typical operating conditions and specific activity of the different samples, the regions in the sintering plant where de novo synthesis may take place were tentatively established.

Reactions of 2,4,6-trichlorophenol on model fly ash: oxidation to CO and CO2, condensation to PCDD/F and conversion into related compounds.

Thermal treatment of 2,4,6-trichlorophenol on a magnesium silicate-based model fly ash in the temperature range between 250 degrees C and 400 degrees C leads predominantly to carbon monoxide and carbon dioxide. The fraction of 2,4,6-trichlorophenol which is oxidized to CO and CO2 increases from 3% at 250 degrees C to 75% at 400 degrees C. Further products are polychlorinated benzenes, dibenzo-p-dioxins, dibenzofurans and phenols. The homologue and isomer patterns of the chlorobenzenes suggest chlorination in the ipso-position of the trichlorophenol. The formation of PCDD from 2,4,6-trichlorophenol and 2,3,4,6-tetrachlorophenol on municipal solid waste incinerator fly ashes and model fly ash were compared and the reaction order calculated.

First Report of Aflatoxin in Dried Yam Chips in Benin.

Dried yam (Dioscorea spp.) chips are widely consumed in Bénin but are often attacked by molds. Invasion of food by Aspergillus flavus may lead to aflatoxin contamination. We report here the result of a survey on the sanitary quality of dried yam chips in Bénin. During July and August 2000, 50 dried yam chips samples were collected from different points in the marketing chain; 10 samples were collected from each of 5 stages: producers, wholesalers, retailers, dried yam-based food sellers and consumers. Aflatoxin content was assayed by the bio-luminescence method (1) after methanol/water extraction. Aflatoxins were detected in all dried yam chip samples, with levels ranging from 2.2 to 200 ppb and a mean value of 14 ppb. An aflatoxin concentration higher than the European Union's maximum residue limit (MRL) of 4 ppb was found in 98% of the samples (N = 50), while 6% had an aflatoxin concentration higher than the World Health Organization's MRL of 20 ppb. Molds were analyzed from two samples, each with aflatoxin levels around 5 ppb, on colony unit medium specific for A. flavus (2). Aspergillus spp. were detected in the inner part of dried yam chips of both samples, with a mean level of 9,000 CFU/g. Fusarium colonies were also present but were not identified to species. References: (1) D. Champiat and J. Larpent. Bio-chimie-luminescence: Principes et Applications. Masson, Paris, France. 1993. (2) P. J. Cotty. Mycopathologia 125:157, 1994.

Spontaneous regression of HIV associated T-cell non-Hodgkin's lymphoma with highly active antiretroviral therapy.

A subcutaneous, T-phenotypic anaplastic large cell lymphoma (CD30/Ki1-positive, EBV positive) was diagnosed in a HIV-infected bisexual man. Without chemotherapy the patient had a sustained long-term remission of this tumor (more than three years) after the initiation of highly active antiretroviral therapy. By PCR analysis of T-cell receptor beta gene rearrangements the tumor was found to be oligoclonal. Improvement of cellular immune function by antiretroviral therapy is the only recognizable factor which may have led to tumor remission. This hypothesis is supported by parallels to EBV associated polyclonal lymphoproliferation in allogeneic transplantat recipients where regression of lymphoma can be induced by reducing immunosuppressive therapy.