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Biomedical subjects

A M Jansen

Publications and source records attributed to A M Jansen.

At least 37 records · Page 2Linked to original sources

Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group.

BACKGROUND: Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. PURPOSE: Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. METHODS: More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. RESULTS: HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors). CONCLUSIONS: Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. IMPLICATION: The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.

Adult↗

High-density-lipoprotein-independent killing of Trypanosoma brucei by human serum.

The cattle pathogen Trypanosoma brucei brucei is morphologically indistinguishable from the human pathogens T.b. rhodesiense and T.b. gambiense. However, unlike the human pathogens, T.b. brucei is lysed by normal human serum (NHS). The trypanolytic factor in NHS co-purifies with high-density lipoproteins (HDL), but its precise nature is unknown. Using a new fluorescence-based viability assay to assess T.b. brucei killing, we find that the HDL-deficient sera from two patients with Tangier disease are as trypanolytic as NHS. Fractionation of the Tangier sera by density ultracentrifugation revealed that the activity resides only in lipoprotein-depleted fractions. Tangier and NHS were also subjected to molecular sieving chromatography, and the activity profiles were identical. Lytic fractions to T. brucei (but not to T. rhodesiense) appeared under two distinct peaks of 100-600 kDa and > 1000 kDa. Neither peak coincided with the position of the major serum lipoproteins, as determined by cholesterol titrations. The high-molecular-mass peak did not contain the HDL-associated apolipoprotein-A1. Further, we did not find that purified apolipoproteins A1 or J are lytic for the trypanosomes. We conclude that the killing of T. brucei by human serum can be independent of HDL.

Animals↗

Trans-sialidase and sialidase activities discriminate between morphologically indistinguishable trypanosomatids.

The expression of trans-sialidase and sialidase activities in the kinetoplastid protozoa was explored as a potential marker to discriminate between the morphologically indistinguishable flagellates isolated from human, insects and vertebrate reservoir hosts. By virtue of the differences observed in the ratios of these enzyme activities, a collection of 52 species and strains comprising the major taxa of these parasites could be separated into four expression types. Type-I parasites express comparable levels of both trans-sialidase and sialidase activities (Endotrypanum species and Trypanosoma lewisi). Type-II parasites express predominantly trans-sialidase activity (Trypanosoma cruzi and Trypanosoma conorhini). Type-III parasites express sialidase activity exclusively (Trypanosoma rangeli and Trypanosoma leeuwenhoeki). Type-IV parasites do not express either activity (Leishmania species and Trypanoplasma borreli). The measurement of trans-sialidase and sialidase activities thus permits the differentiation of parasites frequently found in the same insect vectors that are difficult to distinguish, such as T. cruzi and T. rangeli, or in the same sylvatic vertebrate and invertebrate hosts, such as Leishmania and Endotrypanum.

Animals↗

Trypanosoma cruzi: properties of a clone isolated from CL strain.

BALB/c mice injected i.p. with 2 x 10(6) metacyclic forms of CL-14, a clone isolated from the CL strain of Trypanosoma cruzi, did not show parasitemia as evaluated by direct blood microscopy examination, hemoculture and xenodiagnosis. Moreover, new-born mice (1-2 days old) injected with culture- or insect-derived CL-14 trypomastigotes also displayed negative parasitemia. No mortality was observed in either group of animals. However, despite this apparent non-infectivity, mice injected with clone 14 developed high resistance against a lethal challenge with virulent trypomastigotes. All challenged mice survived and the parasitemia was negative. These results indicate that clone 14 is a very good antigen for the study of acquired immunity in T. cruzi infection and, therefore, a potential candidate for the development of a vaccine against this parasite.

Animals↗

Trypanosoma cruzi in the opossum Didelphis marsupialis: parasitological and serological follow-up of the acute infection.

The opossum Didelphis marsupialis is known to be among the most important wild reservoirs of Trypanosoma cruzi and one in which the trypanosome may go through both the usual vertebrate intracellular cycle in its tissues and an extracellular cycle in the lumen of its scent glands. The species is highly resistant to heavy inocula and, depending on the parasite strain, experimental infections may be permanent or self limited. Aiming to understand the mechanisms involved in this parasite-host interaction we made a study of the acute phase of infection with different T. cruzi strains. Strains F, G-49 and G-327 produced durable infections with relatively high parasitemia and invasion of the scent glands, while equivalent inocula of the Y strain resulted in scanty parasitemia of short duration, no invasion of the SG, and no evidence of persistent parasitism. A smaller inoculum of G-49 produced only subpatent though persistent parasitemia and no invasion of the scent glands. The humoral immune response was less marked in the Y group; among the other groups IgM and IgG antibodies increased to high levels, higher in the G-49 group. The increase in IgG coincided with a drop of parasitemia to subpatent levels. Two opossums inoculated directly in the scent glands with culture forms of the Y strain had a short-lived subpatent parasitemia, but the parasites remained in the glands and serum Ig antibodies reached high levels. Immunoblot analysis showed that the sera of the inoculated opossums recognized few T. cruzi antigens (more in the F strain) in comparison with those of mice. However, with the only exception of those subcutaneously inoculated with the Y strain and including two naturally infected specimens, all the opossum's sera recognized a 90-kDa peptide in all T. cruzi strains. Our results confirm that opossums are able to selectively eliminate some strains of T. cruzi and indicate that the mechanism involved in this selection is probably not related to the humoral immune response. In infections by strains that are able to establish a permanent foothold in opossum tissues, there are indications that IgG antibodies participate in the control of the parasite population of the acute phase but are unable to prevent the chronic phase. It was once more demonstrated that the opossum infected scent glands function as diffusion chambers for parasite antigens but that, on the other hand, the parasites are here protected against the mechanisms developed by the host to control their population.

Acute Disease↗

Murine macrophage cell lines can be ordered in a linear differentiation sequence.

The present study investigated whether transformed macrophage cell lines represent certain stages in macrophage differentiation. Cell surface markers linked to macrophage differentiation were characterized in 11 murine macrophage cell lines and compared with markers on isolated resident and exudate peritoneal macrophages. Furthermore, the capacity of the cell lines to phagocytose latex microspheres was analyzed. This analysis indicated that cell lines arrested at an early differentiation stage were characterized by the expression of the 'immature' markers Thy-1 and MIV 113, and the lack of expression of 'mature' macrophage markers such as Mac-1, Mac-2, and F4/80. More mature cell lines, which do not express 'immature' markers, show an increase in the expression of 'mature' macrophage markers. Furthermore, the expression of the 'mature' markers was found to be correlated with the phagocytic capacity of the cells. We have ordered the cell lines in a linear differentiation sequence based on these data. We propose that this sequence represents various stages in the differentiation of macrophages. This panel of cell lines provides a new model of early macrophage differentiation.

Animals↗

Trypanosoma cruzi in the opossum Didelphis marsupialis: an indirect fluorescent antibody test for the diagnosis and follow-up of natural and experimental infections.

The use of an indirect fluorescent antibody test (IFAT) performed in a "sandwich" technique has demonstrated: (i) the usefulness of the test for the diagnosis of Trypanosoma cruzi infection in the opossum Didelphis marsupialis; (ii) the existence of differences in the serological response of the opossum, that were related to the parasite strain and were clearly evident during the follow-up of experimental infections in laboratory born specimens; (iii) that, despite a good correlation between serological and parasitological examinations, IFAT was the most sensitive diagnostic test used, followed by xenodiagnosis; and, (iv) that in general, the opossum D. marsupialis seems to be a good responder to T. cruzi antigens.

Animals↗

Three different mutations in codon 61 of the human N-ras gene detected by synthetic oligonucleotide hybridization.

The activation of ras genes in naturally occurring tumors has, thus far, been found to be due to mutations in codon 12 or 61 resulting in single amino acid substitutions. We have used highly labeled synthetic oligonucleotides to detect mutations in these codons and to determine the exact position of the mutation. Using this approach we have found three different mutations in codon 61 of the N-ras gene of various human tumor cell lines. In the fibrosarcoma line HT1080 the first nucleotide of the codon is mutated; in the promyelocytic line HL60 the second and in the rhabdomyosarcoma line RD301 the third nucleotide. For RD301 this implies that the normal glutamine residue at position 61 is replaced by histidine. In addition to the mutated N-ras gene the three cell lines have a normal N-ras gene which is indicative of the dominant character of the mutations.

Base Sequence↗

Trypanosoma cruzi in the sylvatic environment: distinct transmission cycles involving two sympatric marsupials.

Thirty-five specimens of Philander frenata and 36 Didelphis marsupialis were captured in the same Atlantic forest area of Brazil between 1992 and 1994. Haemocultures showed that 50% of P. frenata and 60% of D. marsupialis were infected with Trypansoma cruzi. Biological, biochemical and molecular characterization of the isolates suggested 2 distinct transmission cycles of T. cruzi occurred between these 2 sympatric didelphids. The T. cruzi isolates could be distinguished according to their association with each marsupial species. Biochemical characterization (multilocus enzyme electrophoresis) revealed 15 zymodemes; more variability was observed among the P. frenata isolates than among the isolates from D. marsupialis. The course of natural and experimental infection in D. marsupialis and P. frenata was different and suggested that D. marsupialis was more resistant to infection than P. frenata. In the studied area, P. frenata seems to be a more important reservoir of T. cruzi than D. marsupialis, since 40% of the characterized isolates from P. frenata belonged to the T. cruzi II group, which is associated with human infections.

Animals↗

Developmental stages of Trypanosoma (Megatrypanum) freitasi Rego, Magalhães & Siqueira, 1957 in the opossum Didelphis marsupialis (Marsupialia, Didelphidae).

Trypanosoma (Megatrypanum) freitasi, a parasite of marsupials of the genus Didelphis, has been found to undergo in the lumen of the scent (anal) glands of its vertebrate host, a cycle such as usually occurs in the intestinal tract of the insect vectors of trypanosomatids and similar to what has been reported for Trypanosoma (Schizotrypanum) cruzi. The invertebrate host of Trypanosoma freitasi is still unknown. Developmental stages of the trypanosome in its mammalian host, especially the dividing epimastigotes, multinucleate plasmodial forms and rosettes found in the lumen of the scent glands of a naturally infected Didelphis marsupialis are described and illustrated.

Animals↗

Does coenzyme Q10 play a role in opposing oxidative stress in patients with age-related macular degeneration?

To seek some specific biochemical markers of age-related macular degeneration (AMD), coenzyme Q10 (CoQ10) levels were determined in plasma and platelets from 19 exudative AMD patients and 19 age-matched controls. Lipid peroxidation was followed in plasma in vitro after the addition of a free radical initiator. Most patients had lower plasma CoQ10 content than most controls. Plasma from controls showed greater capacity to oppose the oxidative damage. These results support the concept that free radicals play a pathogenic role in AMD and that CoQ10 may have a protective effect.

Aged↗

From a mono to a digenetic life-cycle: how was the jump for flagellates of the family Trypanosomatidae?

It has been found that species of the digenetic genus Trypanosoma as well as species of monogenetic trypanosomatids of insects can grow in the lumen of the scent glands of opossums reproducing the cycle they perform in the intestinal tract of their insect hosts. Based on these findings, speculations are made on the incompletely known cycles of many mammalian trypanosomes and on the evolution of the family Trypanosomatidae.

Animals↗