343 research outputs found
Genotypic resistance tests for the management of the HIV-infected patient with non-B viral isolates
Witness for the prosecution: The dominating HIV-1 subtype in Europe and in the USA is the B subtype, but the prevalence of circulating recombinant forms and non-B subtypes (nBS) in Europe has increased. HIV-1 group O strains are spontaneously resistant to non-nucleoside analogue reverse transcriptase inhibitors (NNRTI) and little is known about the antiretroviral (ARV) drug susceptibility of nBS clinical isolates. Controlled randomized trials showing a clinical benefit of a treatment guided by HIV-1 resistance testing at virological failure have been conducted on subtype B. Thus, the result cannot be simply extended to nBS. In nBS, the frequency or amplification failure is increased, but retesting failed samples with an alternative set of polymerase chain reaction primers improves the success of amplification. The major problem is the reliability of genotypic resistance tests (GRT) owing to misinterpretation of the obtained amino acid mutations, the background sequence in nBS being different from the standard used in the commercial kits or in the web-based HIV-1 resistance interpretation tools. At the moment, no nBS database is available to help in the interpretation of the protease and RT sequence results. Furthermore, the mutational pattern of specific ARV drugs may be different, in particular with subtype C and G. In conclusion, in patients with nBS the indication to for at virological failure may exists, even in the absence of clinical evidence, but the results have to be interpreted by experts with particular caution. Witness for the defence: The extensive variability of HIV-1 has a potential impact on epidemiology, diagnosis, therapy and the prevention of infection. Nine different major subtypes of group M (A-D, F-H, J and K) circulate to varying extents in populations around the globe together with the circulating recombinant forms (CRF) owing to intersubtype recombinations. Although viruses belonging to the HIV-1 B clade are still predominant in Europe, the USA and Australia, an increasing prevalence of non-clade B subtypes and CRF has been reported by several surveys in previously homogeneous clade B countries. As current ARV have been designed using subtype B strains and resistance mutations have been characterized on this subtype, the increasing global spread of HIV subtypes highlights the need to determine the activity of anti-HIV drugs against subtypes or CRF other than subtype B
REPRODUCTIVE FACTORS AND RISK OF ENDOMETRIAL CANCER
The role of reproductive factors in endometrial cancer risk has been analyzed in a case-control study conducted since 1983 in the greater Milan area on 568 women (cases) with histologically confirmed endometrial cancer and 1925 women (controls) who were admitted for acute, nonmalignant, hormonal, gynecologic conditions to hospitals that cover a comparable catchment area. Compared with nulliparous women, parous women had a 30% lower risk of endometrial cancer, but there was no evidence of a decline in risk with increasing number of births. The risk of the disease decreased with number of spontaneous or induced abortions; the multivariate relative risk estimates were, compared respectively with no spontaneous or induced abortions, 0.5 for women with two or more spontaneous abortions and 0.3 for women with two or more induced abortions; both trends in risk were statistically significant. When parous women only were considered, no association emerged between endometrial cancer and age at first birth, but the risk decreased with increasing age at last birth: compared with women whose last birth occurred before age 25, the relative risk was 0.5 for women who were greater-than-or-equal-to 35 years old at last birth, and the multivariate trend in risk was statistically significant. For most of the reproductive factors that were considered, the risk estimates tended to be greater at younger age or among premenopausal women and to flatten off in subsequent strata of age. An association between endometrial cancer and age at first birth was observed in women who were less-than-or-equal-to 49 years old, but not in older groups. The observation that later age at last birth as well as later first birth in younger women decreases the risk of endometrial cancer suggests a short-term protective effect of pregnancy. This finding is consistent with a late-stage (promotional) effect of reproductive factors on endometrial carcinogenesis
Modulation of the locomotory capacity of human large granular lymphocytes
The regulation of the migratory capacity of Percoll-purified large granular lymphocytes (LGL) into nitrocellulose filters was studied in a 2-hr assay with the use of modified Boyden chambers. Compounds that stimulate the natural killer cytotoxic function of LGL, such as interferons (natural β, recombinant αA, recombinant hybrid α A/D, recombinant γ), recombinant interleukin-2, and inactivated streptococci (OK 432), augmented the capacity of LGL to penetrate into filters spontaneously in the absence of chemoattractants in the lower compartment of the chamber. These compounds did not increase the LGL responsiveness to chemoattractants. Phorbol 12-myristate 13-acetate did not appreciably affect the locomotory capacity of LGL but augmented their cytotoxic activity. Thus the cytotoxic function and locomotion of LGL in response to biological response modifiers can be dissociated
CD4 count in HIV infection is positively correlated to interferon-gamma and negatively correlated to interleukin-10 in vitro production
AIDS in a long-term HIV-1-infected patient with a stable high CD4+ cell count and conserved CD4+CD45RO+ subpopulation
Antisense phosphorothioate oligodeoxynucleotides targeted to the vpr gene inhibit human immunodeficiency virus type 1 replication in primary human macrophages
The replication of human immunodeficiency viruses (HIV) in human macrophages is influenced by genetic determinants which have been mapped predominantly to the viral envelope. However, in HIV-2, the vpr gene has also been suggested as an important modulator of viral expression in human macrophages. We synthesized five antisense phosphorothioate oligodeoxynucleotides complementary to the vpr mRNA of HIV-lBa.L, a highly macrophage-tropic viral strain, and measured their effect on HIV-lBa.L replication in primary human macrophages. All of the oligodeoxynucleotides displayed some level of non-sequence-specific inhibition of viral replication; however, only the antisense one had an additional effect on viral production in primary macrophages. Of the five antisense oligodeoxynucleotides tested, only one did not show any additional effect on viral production, whereas all the others inhibited viral replication to a similar degree (70 to 100%). Variation in the degree of inhibition was observed by using five different donors of human primary macrophages. The phosphorothioate oligonucleotides, targeted to the initiating methionine of the Vpr protein, had an inhibitory effect at both 20 and 10,uM only when the size was increased from 24 to 27 bases. Thus, HIV-1 replication in human macrophages is modulated by the expression of the vpr gene, and it is conceivable that vpr antisense oligodeoxynucleotides could be used in combination with antisense oligodeoxynucleotides against other HIV-1 regulatory genes to better control viral expression in human macrophages
The degree of viral suppression predicts the probability of accumulating new drug-mutations at virological failure to the first PI-HAART regimen
Wound Myiasis Caused by Sarcophaga (Liopygia) argyrostoma (Robineau-Desvoidy) (Diptera: Sarcophagidae): Additional Evidences of the Morphological Identification Dilemma and Molecular Investigation
In Mediterranean countries, Sarcophaga (Liopygia) crassipalpis, Sarcophaga (L.) argyrostoma, and Sarcophaga (L.) cultellata share
the same ecological niche and can be responsible of myiasis. In this study, the main morphological characters of a larva found in a
hospitalized woman were described and illustrated by light and SEM microscopy and the features discussed.Then, a fragment within
the mitochondrial encoded cytochrome c oxidase subunit I (coxI) gene of ∼735 bp was amplified and sequenced. The molecular
investigation was necessary to confirm the species Sarcophaga (Liopygia) argyrostoma (99% of identity). Our findings showed that
morphological descriptions of larvae of three Mediterranean species of Liopygia available in several papers might not be clear
enough to allow for comparison and correct identification. Until results of reliable comparative studies of larvae of all three species
will be available, the use of molecular tools is crucial, to avoid misleading or incomplete identification, and in particular when a
myiasis becomes a legal issu
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