Biomedical subjects
Publications and source records attributed to G de-Thé.
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The susceptibilities of different strains of inbred rats to infection with the human T-cell leukemia virus (HTLV-I) after inoculation of human HTLV-I producer cell lines were compared. The Fisher F344 and Brown Norway strains developed the highest antibody response to HTLV-I, while the Lewis and BB strains were low responders. Antibodies against the HTLV-I gag proteins, and env gp21 but not env gp46, were detected in Western blots with sera from HTLV-I-infected Fischer F344 and Brown Norway rats. These sera were inactive in an in vitro syncytium-formation inhibition test. The HTLV-I provirus was detected by polymerase chain reaction in all Fischer F344, and some Lewis and Brown Norway rats, but not in the BB, which lack CD8+ T lymphocytes. The most frequent locations of the HTLV-I provirus in the Fischer F344, Lewis and Brown Norway rats at 12 weeks after infection were the peripheral blood mononuclear cells (PBMC) and spinal cord. In a second experiment in Brown Norway rats, the provirus was again detected in the PBMC of rats at 12 weeks, but not at 22 weeks, and among the other organs tested at 22 weeks the sympathetic nerve ganglia were positive. It is concluded that HTLV-I infection occurs in adult rats, but is suppressed with time.
A study on the incidence of nasopharyngeal carcinoma (NPC) has been performed in the Provence-Alpes-Côte d'Azur (PACA) region, South of France, where Maghrebian migrants represent 10% of the population. During the years 1986-1990, 76 cases of NPC were diagnosed, of which 44 were French by birth, 25 were Maghrebian migrants and 7 were other migrants. We found that 36% of the French patients were either born in endemic areas or had lived there for more than 15 years. Standardized annual incidence rates of NPC among Maghrebian migrants remained close to those observed in North Africa, while, standardized annual incidence rates for French by birth in the PACA region were similar to those observed in cancer registries in other regions of France and countries of low incidence. However, for males of French origin born in Maghrebian countries, the incidence of NPC (all cases being of undifferentiated type) was 5.7 times higher than that of males of French origin born in France (p = 0.00001). These results favor a critical role of environmental factors in the risk of NPC.
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The Epstein-Barr virus (EBV) is a ubiquitous Herpes virus which causes infectious mononucleosis and is associated with such different neoplasms as Burkitt's lymphoma and nasopharyngeal carcinoma. EBV latently infects its target cells; nevertheless, evidence of viral replication in NPC tumours has been uncovered. Among the EBV transactivators, the ZEBRA protein plays a crucial role in switching the virus from a latent to a productive mode. ZEBRA protein was produced using a eukaryotic expression vector: the open reading frame containing the BZFLI cDNA has previously been inserted down-stream from the adenovirus major late promoter leading to expression of a 38-kDa nuclear protein. We performed serological studies by employing ZEBRA protein expressed in human cells for immunofluorescence and Western-blot assays. We were able to detect IgG anti-ZEBRA antibodies (IgG/ZEBRA) in 87% of NPC patients. These antibodies were absent in control sera; IgG/ZEBRA antibodies can be proposed as a useful marker for diagnosis of NPC tumors.
Representative samples of preserved foods collected from high-risk areas for nasopharyngeal carcinoma were assayed for capacity to induce Epstein-Barr virus (EBV) by measuring induction of the DR promoter gene or of genes for early antigens in Raji cells. The two assays gave concordant results, but the DR induction assay detected EBV-inducing substances at lower concentrations and more reproducibly. Three of 17 preserved food items were active in both assays; they were also weakly mutagenic in the SOS chromotest and contained low or moderate levels of volatile N-nitrosamines. After in-vitro nitrosation, the levels of mutagens and nitrosamines increased, whereas EBV-inducing activity was unchanged or decreased. Thus, EBV inducers appear to be a different class of substances from mutagens and volatile N-nitrosamines but could act with them in the etiology of nasopharyngeal carcinoma.
We conducted a case-control study of nasopharyngeal carcinoma (NPC) in Tunisia, on diet, dietary patterns and life style, the characteristics of which had been defined by an anthropological study. Eighty incident cases, diagnosed in Tunisia between November 1986 and November 1987, were each matched for sex, age and place of residence to 2 controls. The subjects were asked for dietary data referring to the year preceding the diagnosis of NPC and, with help of their families, during childhood and after weaning. After adjustment for an empirical living conditions score, the following food items were found to be associated with an increased risk for NPC: preserved spiced meat (quaddid), basic stewing preparation (mixture of red and black pepper, garlic, oil, caraway and coriander), and harissa (red pepper, olive oil, garlic, caraway, salt) taken with bread as a snack during childhood and youth. Moreover, subjects who had been directly weaned from mother's milk on to an adult diet were found to be at higher risk for NPC.
Seventeen patients with adult T-cell leukemia (ATL) and 21 with tropical spastic paraparesis/human T-cell leukemia/lymphoma virus type I (HTLV-I)-associated myelopathy (TSP/HAM) were observed during a 3-yr survey (1986-1988) in some hospitals in Paris, France. Most of them were black, originating from high-HTLV-I-endemic areas (West Indies or Africa), but two cases of TSP/HAM occurred in French Caucasians. In one case, the patient acquired the virus from a transfusion during a cardiac transplantation. Most of the ATL cases were diagnosed as acute leukemia or lymphoma, with a proliferation of CD2+, CD3+, CD4+, CD8-, DR+, and CD25+ lymphoid cells. Only three cases were diagnosed as a smoldering ATL. All of the TSP/HAM cases exhibited a spastic paraparesis with a chronic and slow evolution and high HTLV-I antibody titers in serum and cerebrospinal fluid, with a high HTLV-I antibody index and specific HTLV-I immunoglobulin = oligoclonal bands. In TSP/HAM, a high percentage of DR-expressing cells (15 to 40%) was found, with a slightly elevated CD4/CD8 ratio. This was associated with the presence of 1 to 10% abnormally shaped nuclei in lymphoid cells and a polyclonal integration of HTLV-I proviruses in these peripheral blood mononuclear cells. On the contrary, a clonal integration was always found in the ATL malignant cells (leukemic, lymph node, and cutaneous infiltrate). Long-term interleukin 2-dependent T-cell lines (CD2+, CD3+, CD4+, and WT31+) with activated T-cell markers (CD25+ and DR+) producing HTLV-I were established from ATL and TSP/HAM peripheral blood mononuclear cells.
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The testing for human immune deficiency virus type 2 (HIV-2) antibodies of 794 sera collected in July-August 1985 in the four regions of Korhogo, Bondoukou, Man, and Bouaké in Ivory Coast and the collection and testing for HIV-1 and HIV-2 antibodies of 1,126 sera collected in July-August 1987 in the same regions and age groups showed a remarkable stability in the prevalence of infection by these two retroviruses (0.7 and 0.4% in 1985 vs. 0.9 and 0.2% in 1987, respectively, for HIV-1 and HIV-2) in rural areas. In contrast, the increase in prevalence of both HIV-1 (from 1 to 1.9%) and HIV-2 (from 0.8 to 1.3%) from 1985 to 1987 in the urban population was accompanied by a sharp increase during these 2 years of the number of acquired immune deficiency syndromes in regional hospitals.
Different Ivorian population groups were comparatively tested for antibodies to HTLV-1, HIV-1, and HIV-2. They included 1,334 healthy individuals, 176 unselected medical patients in regional hospitals, 149 female prostitutes, and 65 males with a sexually transmitted disease (STD) collected in 1987 from four regions (east, north, west, and central). The HTLV-1 prevalence averaged 1 to 2.7% in the different regions, without significant increase in sexually overexposed groups. Furthermore, in Dabou Protestant Hospital, 60 km west of Abidjan, 414 blood donors, 109 asymptomatic HIV-positive individuals, and 181 AIDS clinical cases were also tested. While a significant increase in the prevalence of HTLV-1 antibodies was observed only in AIDS patients. HIV-1 and HIV-2 prevalence increased, as expected, from a low rate (2.4%) in the general population to an intermediate rate (13-15%) in blood donors and unselected hospitalized patients and to a high rate (35%) in prostitutes and STD male patients.
HTLV-I is associated with tropical spastic paraparesis (TSP) in the Caribbean area and with certain chronic myelopathies termed HAM (HTLV-I-associated myelopathy) in Japan. In order to investigate the situation in Africa, we tested for HTLV-I, but also for HIV-1 and HIV-2 antibodies, 94 patients with epidemic spastic paraparesis (ESP) from Zaire and Tanzania, 26 cases of sporadic spastic paraparesis (SSP) and 21 cases of tropical ataxic neuropathy (TAN), both from Ivory Coast, and 319 unselected neurological patients from Ivory Coast, Congo, and Tanzania. While none of the 94 ESP cases nor any of the 21 TAN patients exhibited antibodies to any retrovirus, 4 of the 26 sporadic spastic paraparesis patients had high HTLV-I antibodies in their sera and cerebrospinal fluid (CSF). Three of those were clinically and immunologically identical to TSP, as observed in persons from the Caribbean region, and the fourth case, a poorly explored chronic pyramidal syndrome, could also represent a TSP. Only one of these four cases originally had HIV-1 antibodies. Among the 319 unselected patients, only 5 (1.6%) had HTLV-I antibodies, but 32 (10%) had HIV-1 antibodies and 14 (4.4%) had HIV-2 antibodies, with a number of combined infections, indicating that retroviruses represent potentially important etiological agents for African neurological diseases.
Tropical spastic paraparesis (TSP), a neuromyelopathy predominantly involving the pyramidal tract and commonly observed in tropical and equatorial areas, was recently found to be associated with human T lymphotropic virus type I (HTLV-I). We investigated sera and cerebrospinal fluid (CSF) from 19 patients with TSP who were from the Caribbean area, French Guiana, and Africa. Our results showed an elevated intra-blood-brain barrier IgG synthesis rate and an elevated IgG index, with an increased HTLV-I antibody-to-albumin ratio and the presence of CSF oligoclonal bands in the majority of the patients. These data, in association with similar HTLV-I antibody patterns between patients with TSP who were from these three regions, strengthen the probable etiologic role of HTLV-I in the pathogenesis of such chronic neuromyelopathies.
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On the basis of anthropological pilot studies on diet in Tunisia, south China and Greenland, food items consumed frequently by these populations at high risk for NPC were analysed for volatile nitrosamines using gas chromatography combined with a thermal energy analyzer. Relatively high levels of N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP) were detected in Tunisian stewing base ("Touklia") and dried mutton preserved in olive oil ("Qaddid"). NDMA was also detected at levels ranging from trace amounts to 133 micrograms/kg in several Chinese salted and dried marine fish and in Greenland dried, unsalted fish preparations. NPYR and NPIP were also occasionally detected in several vegetables fermented in brine collected in Tunisia and China. The possible role of nitrosamines in the etiology of NPC is discussed.
Tropical spastic paraparesis (TSP) is a common myeloneuropathy with primary and predominant involvement of the pyramidal tract and minimal sensory loss. The epidemic form of TSP is related to toxic nutritional factors, but the endemic form occurs in clusters in tropical areas, especially in India, Africa, the Seychelles, Colombia, and areas of the Caribbean. We describe the clinical and epidemiological features of 25 TSP patients from Martinique (French West Indies) with serum antibodies to human T-lymphotropic virus type I (HTLV-I). Furthermore, all 11 patients who were seropositive for HTLV-I had specific HTLV-I antibodies in their CSF. All were women. The age of onset varied from 25 to 60 years (mean, 45 years). The main clinical features are spastic paraparesis or paraplegia with spasticity of the upper limbs, minimal sensory loss, and bladder dysfunction. Minimal estimated incidence and prevalence are 1 per 100,000 inhabitants per year and 8 per 100,000, respectively. Seventeen percent of the relatives of patients with HTLV-I-associated TSP have HTLV-I antibodies (1 husband and 7 children). In Martinique, the prevalence of HTLV-I antibodies in the general population is about 2% and reaches 10% for neurological disorders other than TSP. Since our initial report, the association between spastic paraparesis and HTLV-I has been confirmed in Jamaica, Colombia, and Japan, suggesting the neurotropism of this lymphotropic human retrovirus.
Fifty-four samples of foods consumed frequently in Tunisia, southern China and Greenland, all high-risk areas for nasopharyngeal carcinoma (NPC), were analysed for the presence of volatile nitrosamines by gas chromatography (GC) combined with a thermal energy analyser (TEA). Relatively high levels of N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR) were found in Tunisian stewing base (touklia) and dried mutton preserved in olive oil (qaddid). In one Chinese salted and dried fish sample, a high level of NDMA (133 micrograms/kg) was detected, but for the 14 others the levels ranged from undetectable to 14 micrograms/kg, with a mean of 3 micrograms/kg. Similarly high levels of NDMA, were found in Eskimo dried, unsalted fish samples. NDMA, NPIP and NPYR at various levels were present in Chinese vegetables fermented in brine. The possible role of nitrosamines in the etiology of NPC is discussed.
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