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Biomedical subjects

V Piguet

Publications and source records attributed to V Piguet.

At least 19 recordsLinked to original sources
PubMed2006

[Drugs--of molecules and relationships].

Drugs have always been both medicine and poison. Their function is cure but they can also kill; they have desired but also adverse effects. Drugs can be defined as technical objects which use is inserted within a set of representations, practices and social relationships. Acting as a mediator--and sometimes as an issue--in the relationship, medication and its use are far from the rational management of drugs as defined by public health authorities. The matter at stake can also be the legitimation of illness or pain. As a means of legitimation, psychotropic drugs raise specific questions as there is no objectivation of symptoms, be them mood changes or pain, aside from the patient's account.

Decision Making↗
PubMed2005

Receptor modulation in viral replication: HIV, HSV, HHV-8 and HPV: same goal, different techniques to interfere with MHC-I antigen presentation.

Evasion of host immunity is a common objective of viruses that cause chronic infections. Viruses involved in sexually transmitted infections constitute no exception to this phenomenon. HIV, HPV, HSV, and HHV-8 subvert the class I major histocompatibility complex (MHC-I) antigen presentation pathway, thereby evading the cellular immune response. Although the goal of these viruses is the same and efficient MHC-I downregulation in infected cells is achieved, their techniques vary considerably. Whether viral inhibition occurs at the transcriptional level, during assembly of MHC-I complexes in the endoplasmic reticulum, during its journey to the cell surface, or after reaching the cell surface, each one of these viruses ingeniously achieves MHC-I downregulation and avoids the cellular immune response. Unraveling the mechanisms of interference with MHC-I antigen presentation employed by these viruses is not only crucial to understand their pathogenesis, but also reveals novel mechanisms of regulation of cellular receptors. When employed as modulators of cellular trafficking pathways, viruses become tools to dissect fundamental cell processes. In return, the precise dissection of these processes may offer new weapons against the ruses viruses employ to propagate and establish chronic infections.

Antigen Presentation↗
PubMed2005

Extensive annular verrucous late secondary syphilis.

We report an illustrative case of an apparently healthy 38-year-old man with a past history of alopecia universalis who developed extensive, slightly pruritic, infiltrated annular verrucous lesions of the scalp, perioral, lumbar, perianal and genital areas over a 6-month period. The combination of an unusual clinical presentation, positive syphilis serology and rapid response to penicillin therapy was consistent with a diagnosis of extensive annular and verrucous late secondary syphilis. We present this case to illustrate a rare and potentially misleading clinical feature of late secondary syphilis, a disease considered to be of the past but still present in today's practice.

Adult↗
PubMed2004

[Treatment of cutaneous human papilloma virus, poxvirus and herpes simplex virus infections with topical cidofovir in HIV positive patients].

INTRODUCTION: Cidofovir (Vistide) is an antiviral marketed for the treatment of cytomegalovirus retinitis. Clinical efficacy has been reported with its broad antiviral spectrum that includes poxvirus, human papilloma virus and Herpes simplex. In immunodepressed patients, these infectious dermatoses are often recurrent and resistant. In an open study, we assessed the efficacy and clinical tolerance of cidofovir gel at 1 p. 100. PATIENTS AND METHODS: Twelve HIV-infected adults were included. Cidofovir gel at 1 p. 100 was applied directly on the lesions, once a day, for two weeks on the molluscum and condylomas, four weeks on the warts and one week on the chronic herpes. RESULTS: Four patients presented with warts and 3 of them with verruca plana. In 2 of the verruca plana patients, regression was complete although relapse was observed. Two failures were noted. Local application of the gel was not tolerated by one patient suffering from condylomas of the penis. Four patients presented with molluscum contagiosum. Two complete regressions with strong local reaction and two partial regressions were observed. The latter two patients exhibited severe immunodepression, one of them subsequently received infusions of cidofovir. Two women suffering from vulvar and perianal herpes resistant to acyclovir were treated for one week with cidofovir gel at 1 p. 100: no response was obtained. One of the patients stopped treatment because of local intolerance. A third, less immunodepressed, woman responded partially. COMMENTS: In HIV-positive patients, cidofovir in topical form appears to be indicated in extensive and confluent molluscum contagiosum. However, the effect occurs at the cost of local inflammation. The results are disappointing in papillomavirus lesions and in chronic acyclovir-resistant herpes ulcerations, efficacy is debatable.

Administration, Topical↗
PubMed2004

Fulminant herpetic sycosis: atypical presentation of primary herpetic infection.

Fulminant herpetic sycosis is a rare but well-known manifestation of herpes simplex virus (HSV) infection occurring in the context of viral recurrence in immunodepressed patients. We present here the case of a 32-year-old male patient, without notable medical history, who developed papulovesicular lesions of the beard accompanied by fever, painful cervical lymphadenopathy and odynophagia, with a clinical evolution that was initially unfavourable under antibiotic treatment. The diagnosis of herpetic sycosis was established by means of direct immunofluorescence and culture which confirmed positivity for HSV-1 and serologies compatible with a primary viral infection. No sign for a latent immune deficit was found at the time of investigations. The clinical evolution was rapidly favourable with administration of intravenous aciclovir for 1 week. To our knowledge, herpetic sycosis as a presentation of primary viral infection has not been reported previously. The possibility of a herpetic sycosis of the beard must be considered in the case of non-response to antibiotic or antifungal treatment.

Acyclovir↗
PubMed2003

Clinical pharmacology and rationale of analgesic combinations.

BACKGROUND AND OBJECTIVE: Oral fixed drug combination analgesics have potential advantages over monotherapy, but these can only be attained through careful design. RESULTS: The main reasons for developing combination analgesics are to gain efficacy and to reduce toxicity. Analgesic combinations interact pharmacokinetically, or pharmacodynamically, or both, in positive or negative terms. The t(max) value for both enantiomers of tramadol occur two hours following administration, and that for the active, (+)-M1 metabolite occurs after three hours. Thus, pairing tramadol with acetaminophen, a rapid-onset analgesic, represents a pharmacokinetically rational combination. Analgesic combinations should satisfy two important pharmacodynamic criteria: the components of the combination should display additive or synergistic analgesia; and this interaction should allow lower doses of each substance to be used in combination, resulting in an improved safety profile. Clinical studies of the pharmacodynamic between oral tramadol and acetaminophen in third molar extraction and cold pressor models have provided evidence that this combination provides better efficacy than either individual component of the combination. CONCLUSIONS: In summary, combination analgesics can play a valuable role in pain management. However, dubious combinations (directed against the same targets or with unwanted interactions) and 'old fashioned' fixed-dose multiple analgesic agent combinations should be avoided. Fixed-dose combination analgesics are of value only when they have been developed according to rational pharmacokinetic and pharmacodynamic criteria, and when claims for their benefits have been supported by evidence-based data and well-designed clinical studies.

Analgesics↗
PubMed2002

Optimized lentiviral transduction of erythroid precursors from healthy adults and patients with myelodysplastic syndromes.

Lentivectors, derived from human immunodeficiency virus-1 (HIV-1), represent a novel investigational and therapeutic tool for targeting hematopoietic progenitor cells. We describe a new protocol whereby we achieved a highly efficient lentiviral transduction of erythroid precursor cells originating from the bone marrow of healthy adults and patients with myelodysplastic syndromes (MDS). CD34(+) stem cells from healthy subjects were cultured with erythropoietin, IL-3 and stem cell factor, and thereby expanded approximately 300-fold. When these cultures were transduced with a lentiviral vector expressing GFP as a reporter gene, 70% glycophorin(+) cells were GFP(+). Although proliferation and levels of transduction were reduced in cultures of CD34(+) stem cells from patients with myelodysplastic syndromes, 50% of glycophorin(+) cells became GFP(+), amongst which 30% were sideroblastic erythroid precursors. This study demonstrates that lentiviral vectors are capable of efficiently transducing MDS precursors and offers new perspectives to investigate the influence of specific genes on normal erythroid differentiation. This may eventually help to correct defects in patients suffering from myelodysplastic syndromes.

Adult↗
PubMed2002

Advances with analgesics and NSAIDs for the treatment of spinal disorders.

One of the major developments with regard to chronic non-malignant pain in these last few years has been a better understanding of the mechanisms that act to maintain pain, while inferences about the pathophysiology have facilitated therapeutic decision-making. This chapter reviews the strength of evidence for the therapeutic effect of pharmacological symptomatic approaches using non-steroidal anti-inflammatory agents, opioids and co-analgesics in acute and chronic back pain with an emphasis on the results of randomized controlled trials as well as on the need for long-term comparative trials of drug efficacy, toxicity and compliance.

Acute Disease↗
PubMed2001

Living in oblivion: HIV immune evasion.

The human and simian immunodeficiency viruses (HIV and SIV, respectively) are members of the lentiviridae subgroup of retroviruses that cause a progressive failure of the host immunological functions culminating in the clinical collapse known as AIDS, or acquired immunodeficiency syndrome. In the absence of antiviral therapy, this course is inexorable in spite of an initially vigorous immune response. Two fundamental characteristics of the biology of primate lentiviruses explain this apparent paradox. First, HIV and SIV infect CD4(+)targets such as helper T lymphocytes and macrophages, that is, cells that normally play an essential role in the emergence and maintenance of an effective antiviral response. Second, these viruses have evolved a number of strategies to evade control by the immune system. These include mutational escape, latency, masking of antibody-binding sites on the viral envelope, downmodulation of the class I major histocompatibility complex (MHC-I), and upregulation of the Fas ligand on the surface of infected cells. Examining the mechanisms of these phenomena not only helps to understand how HIV wins its war against the immune system, but it also suggests as yet unexploited avenues to combat the virus through therapies and to develop a vaccine.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1beta, and the production of interferon gamma in the absence of IL-12 during DC-T cell cognate interaction: a new role for Fas ligand in inflammatory responses.

Ligation of the Fas (CD95) receptor leads to an apoptotic death signal in T cells, B cells, and macrophages. However, human CD34(+)-derived dendritic cells (DCs) and mouse DCs, regardless of their maturation state, are not susceptible to Fas-induced cell death. This resistance correlates with the constitutive expression of the Fas-associated death domain-like IL-1beta-converting enzyme (FLICE)-inhibitory protein (FLIP) ligand. We demonstrate a new role of Fas in DC physiology. Engagement of Fas on immature DCs by Fas ligand (FasL) or by anti-Fas antibodies induces the phenotypical and functional maturation of primary DCs. Fas-activated DCs upregulate the expression of the major histocompatibility complex class II, B7, and DC-lysosome-associated membrane protein (DC-LAMP) molecules and secrete proinflammatory cytokines, in particular interleukin (IL)-1beta and tumor necrosis factor alpha. Mature DCs, if exposed to FasL, produce even higher amounts of IL-1beta. Importantly, it is possible to reduce the production of IL-1beta and interferon (IFN)-gamma during DC-T cell interaction by blocking the coupling of Fas-FasL with a Fas competitor. Finally, during cognate DC-T cell recognition, IL-12 (p70) could not be detected at early or late time points, indicating that Fas-induced, IFN-gamma secretion is independent of IL-12.

Apoptosis↗
PubMed2000

HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes.

Major-histocompatibility-complex (MHC) proteins are used to display, on the surface of a cell, peptides derived from foreign material - such as a virus - that is infecting that cell. Cytotoxic T lymphocytes then recognize and kill the infected cell. The HIV-1 Nef protein downregulates the cell-surface expression of class I MHC proteins, and probably thereby promotes immune evasion by HIV-1. In the presence of Nef, class I MHC molecules are relocalized from the cell surface to the trans-Golgi network (TGN) through as-yet-unknown mechanisms. Here we show that Nef-induced downregulation of MHC-I expression and MHC-I targeting to the TGN require the binding of Nef to PACS-1, a molecule that controls the TGN localization of the cellular protein furin. This interaction is dependent on Nef's cluster of acidic amino acids. A chimaeric integral membrane protein containing Nef as its cytoplasmic domain localizes to the TGN after internalization, in an acidic-cluster- and PACS-1-dependent manner. These results support a model in which Nef relocalizes MHC-I by acting as a connector between MHC-I's cytoplasmic tail and the PACS-1-dependent protein-sorting pathway.

Animals↗
PubMed1999

The HIV Nef protein alters Ca(2+) signaling in myelomonocytic cells through SH3-mediated protein-protein interactions.

Human immunodeficiency virus Nef plays an important role in AIDS pathogenesis. In addition to the well known down-regulation of cell surface receptors (CD4, MHCI), Nef is able to alter cellular signaling. Of particular interest for this study is the ability of Nef to bind with a very high affinity to SH3 domains of myelomonocyte-specific protein-tyrosine kinases of the Src family (Src-like PTK). We have therefore investigated Ca(2+) signaling in HL60 cells retrovirally transduced with wild type Nef or with a Nef mutant deficient in the SH3-interacting proline-rich motif (Nef((PXXP)4(-))). In differentiated HL60 cells, Nef markedly altered cellular Ca(2+) signaling; the amount of intracellularly stored Ca(2+) was increased, and as a consequence, store-operated Ca(2+)-influx was decreased. This effect was not observed in undifferentiated HL60 cells or in CEM T-lymphocytes and correlated with the differentiation-induced up-regulation of Src-like PTK. The Nef effect on Ca(2+) signaling depended entirely on the integrity of its PXXP motif. The Src-like PTK p56/59(hck) co-immunoprecipitated with both Nef and with the inositol 1,4,5-trisphosphate receptor, providing a possible mechanistic link between the viral protein and intracellular Ca(2+) stores of the host cell. Collectively, our results demonstrate that the human immunodeficiency virus 1 Nef protein manipulates intracellular Ca(2+) stores through SH3-mediated interactions in myelomonocytic cells.

Calcitriol↗
PubMed1999

Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes.

The Nef protein of primate lentiviruses downregulates the cell surface expression of CD4 through a two-step process. First, Nef connects the cytoplasmic tail of CD4 with adaptor protein complexes (AP), thereby inducing the formation of CD4-specific clathrin-coated pits that rapidly endocytose the viral receptor. Second, Nef targets internalized CD4 molecules for degradation. Here we show that Nef accomplishes this second task by acting as a connector between CD4 and the beta subunit of COPI coatomers in endosomes. A sequence encompassing a critical acidic dipeptide, located nearby but distinct from the AP-binding determinant of HIV-1 Nef, is responsible for beta-COP recruitment and for routing to lysosomes. A novel class of endosomal sorting motif, based on acidic residues, is thus revealed, and beta-COP is identified as its downstream partner.

Amino Acid Sequence↗