Hepatitis C virus is not a cofactor for Kaposi's sarcoma development in HIV-infected patients.
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HIV Infections↗
Biomedical subjects
J P Van Vooren
Publications and source records attributed to J P Van Vooren.
Stimulation of Kaposi's sarcoma cell growth by urine from women in early pregnancy, the current source for clinical-grade human chorionic gonadotropin preparations.
Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi's sarcoma (KS) cells. However, the results of clinical studies using commercial hCG preparations KS remain highly contradictory. More particularly, some hCG preparations could have a paradoxical growth effect on KS. Such discrepant results may be explained by the fact that the anti-KS activity is not associated with hCG itself but with one or more factors that are co-purified with the hormone. We found here that crude urine from first trimester pregnant women, the current source for commercial hCG, had a growth stimulatory effect on KS cells. By contrast, urine from last trimester pregnant women, from non-pregnant young women, from menopausal women and from men exhibited neither a growth stimulatory nor a growth inhibitory effect on KS cells. The amplitude of this pregnancy urine-associated pro-KS activity/hCG unit was higher than that achieved with clinical-grade hCG preparations. Partial co-purification of pregnancy-associated factors during the extraction procedure of commercial hCG from urine may explain the pro-KS activity achieved with some hCG preparations. We, therefore, suggest a cautious use of hCG purified from pregnancy urine for the treatment of KS.
Cell Division↗
High-dose chemotherapy and autologous CD34-positive blood stem cell transplantation for multiple myeloma in an HIV carrier.
The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-positive patients is poorly documented. There are uncertainties concerning the optimal management of this rare disorder. We report on the use of myeloablative chemotherapy with autologous stem cell transplantation in an HIV-positive patient with multiple myeloma.
Acquired Immunodeficiency Syndrome↗
Enhancement of classic Kaposi's sarcoma growth after intralesional injections of desferrioxamine.
We have previously shown that iron may be involved in the pathogenesis of Kaposi's sarcoma (KS) and that the iron chelator desferrioxamine (DFO) inhibits the growth and induces the apoptosis of KS cells in vitro. We treated an 85-year-old man with classic KS with 5 weekly intralesional injections of DFO and observed the opposite effect in vivo. The DFO-treated lesion was characterised by the development of numerous KS papules within the drug diffusion area, whereas no change was noted in untreated or control saline-treated lesions. This suggests that intralesional iron chelators are not indicated in patients with KS.
Aged↗
Treatment of Kaposi's sarcoma with human chorionic gonadotropin.
Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi's sarcoma (KS) cells. However, the mechanism of the anti-KS activity achieved with these preparations remains unclear. The results of clinical studies using commercial hCG preparations in human KS are also highly contradictory. The apparent controversy between different studies may be due to the fact that pro- and anti-KS components are present in varying proportions in different hCG preparations. As certain hCG preparations could not only lack the ability to control KS but also contain some contaminant KS growth factor(s), we suggest a cautious use of crude hCG for the treatment of KS.
Chorionic Gonadotropin↗
Human herpesvirus 8 investigations: a role in the clinical management of Kaposi's sarcoma?
Kaposi's sarcoma (KS) is a vascular tumour associated with infection by human herpesvirus 8 (HHV-8). Most of the recent studies on KS have focused on the epidemiology and molecular biology of HHV-8. However, the contribution of virological investigations into HHV-8 to the clinical management of KS has been poorly evaluated so far. From a diagnostic point of view, HHV-8 currently appears as a useful tool for distinguishing KS from its mimics. Seroconversion to antibodies against HHV-8 may predict the development of KS in susceptible individuals, and reduction of HHV-8 viraemia is associated with therapies effective against KS. Further prospective studies are still required to determine the role of serological or genotypic investigations into HHV-8 in the prevention of KS and in KS response to therapy.
Antiviral Agents↗
[Medically assisted reproduction in couples carrying the human immunodeficiency virus].
Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication, and a growing number of them want to have children. The benefit of resorting to assisted procreation and the contamination prevention strategies, throughout pregnancy, are summarized as well as the changes in ethical considerations. The balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child, has evolved towards a growing interest for medical intervention in order to avoid the risks of spontaneous conception outside health care structures. We are presenting the medical structure adapted at Erasme hospital and the 38 first requests taken into account by our pluridisciplinary team. This approach, which is coherent from a scientific point of view, respects both the autonomy of people, carrying HIV as well as the essential interest of the child, in being born uninfected, and also has the enormous advantage of allowing access to parenthood without destroying the consistency and coherence of the message of prevention of sexual contamination.
Carrier State↗
[The immunodeficiency treatment unit].
Physicians of the unit have first taken care of patients with acquired Immunodeficiency in 1981. We have become an independent "Reference Centre" in 1998. The multidisciplinary team follows more than 300 patients on a regular basis. AIDS has been amply publicized, but other immuno-deficiencies have not. Primary immunodeficiencies are "orphan" diseases; they can be as serious, or more severe even, than AIDS. About 60 patients with "PID" are followed by the team. We are involved in research, and have participated in the identification of a mutation of an HIV co receptor that protects against HIV infection. We also studied the pathogenesis of Kaposi's sarcoma, and the immunological basis of adverse reactions to intravenous gammaglobulins.
Allergy and Immunology↗
[NTBR (Not to Be Resuscitated) in 10 questions].
The term "Not To Be Resuscitated" or "NTBR" is largely used in hospitals in the setting of therapeutic limitations. However, interpretations of this term are sometimes very different. The objective of this article is to define the exact meaning of "NTBR", namely, no resuscitation only in case of cardiac arrest. The rules for therapeutic limitation are also defined.
Humans↗
Immunologic and virologic response after tetanus toxoid booster among HIV-1- and HIV-2-infected Senegalese individuals.
Twelve HIV-1-infected, nine HIV-2-infected patients and eight HIV-negative subjects were given a 40IU booster dose of tetanus toxoid (TT). Blood was collected on days 0, 7 and 30 after immunization. Changes in HIV-1 or HIV-2 RNA load were evaluated by nested PCR. TT-IgG antibody levels were quantified by ELISA. CD4 cell counts as well as activation, memory and maturation markers of T lymphocyte subsets were determined by flow cytometry. The induction of apoptosis was investigated using 7-aminoactinomycin D (AAD) and propidium iodide (PI) staining. Proliferative responses to TT and pokeweed mitogen (PWM) were determined by the level of [(3)H] thymidine incorporation. Seven and 30 days after immunization, there was no detectable increase in HIV-1 or HIV-2 plasma load. There were also no changes in CD4 cell counts, CD69, HLA-DR and memory CD45RO or naive CD45RA antigens. Immunization did not increase the spontaneous apoptosis of peripheral blood mononuclear cells (PBMCs), CD4+ and CD8+ T cells subsets neither in controls nor in HIV-infected patients. Similarly, apoptosis induced in vitro by PWM or by the specific TT recall antigen did not vary during the study period. The proliferative response to PWM and to the TT recall antigen was decreased both in HIV-1- and HIV-2-infected patients compared to HIV-negative controls. Immunization significantly increased the TT-IgG levels in healthy controls and in HIV-infected patients. However, the anti-TT-IgG response, as measured by the fold-increase index between days 0 and 30, was significantly higher in healthy controls than in HIV-1- (P=0.036) and HIV-2-infected patients (P=0.003). In conclusion, we found no deleterious immunologic or virologic effect was detected in healthy HIV-1- and HIV-2-infected individuals after antigenic challenge with a TT booster. However, the response to TT vaccination was lower in HIV-1- and in HIV-2-infected individuals than in healthy HIV-negative controls.
Adult↗
Cultured Kaposi's sarcoma tumor cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1.
BACKGROUND: HIV-1 is known to play a critical role in the pathogenesis of AIDS-associated Kaposi's sarcoma (KS). However, it remains controversial whether KS cells are target cells for HIV infection. The aim of this study was to investigate the expression of chemokine receptors in KS cell cultures and to determine whether these cells can be infected by HIV-1. MATERIAL AND METHODS: KS-derived cells and KS-Y1 cells were investigated using RT-PCR for the expression of CD4, CCR3, CCR5, CCR8 and CXCR4 mRNA. HIV infectivity of these cells was determined by p24 antigen and HIV-1 RNA production, as well as by HIV-1 DNA integration. RESULTS AND DISCUSSION: With the exception of CCR8 which is expressed by KS-derived spindle cell cultures but not by KS-Y1 cells, unstimulated KS cells express no significant levels of CD4, CCR3, CCR5 or CXCR4 mRNA. HIV infectivity assays showed that KS cells were unpermissive to HTLVIIIB and JRFL strains. Although the expression of CXCR4 mRNA could be upregulated by interleukin-1beta, stimulation of KS cells by this cytokine did not allow infection by HIV-1. CONCLUSIONS: This shows that KS cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1. Other cell types making up KS lesions, such as inflammatory cells, are likely to represent the source of HIV-1 products cooperating to promote KS development and progression.
Actins↗
[Medically assisted reproduction and the desire for a child by HIV infected couples: has the time for a change in attitude come?]].
Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication. A growing number of them want to have children. Medical possibilities for preventing contamination of the partners of seropositive men through assisted reproduction and of children thanks to antiviral medicines during pregnancy are summarized. These changes result in ethical considerations which lead the authors to question the conventional systematic medical advise against pregnancy and has encouraged them to assist reproduction for a number of these couples. Today, the balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child has tilted towards medical intervention. It would seem legitimate today to intervene in the most favourable situations rather than see these couples take the risk of spontaneous conception outside health care structures. This implies to adapt medical structure (separate laboratory, appropriate procedure, precise protocols). This approach, which is coherent from the scientific point of view, respects both the autonomy of people carrying HIV as well as the essential interest for the child, in "being" born uninfected and also has the enormous advantage of allowing access to parenthood without destroying the consistency of the message of prevention of sexual contamination.
Anti-HIV Agents↗
Early- and late-stage Kaposi's sarcoma-derived cells but not activated endothelial cells can invade de-epidermized dermis.
Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.
Cell Division↗
Iron induces Bcl-2 expression in human dermal microvascular endothelial cells.
Iron is suspected to be involved in the induction and/or progression of various human tumors. The present study was designed to investigate the effects of iron on endothelial cells, keeping in mind that the homeostasis of microvessels plays a critical role in neo-angiogenesis. Applying a model of human dermal microvascular endothelial cell terminal differentiation and death induced by serum deprivation, we found that iron salts (iron chloride and ferric nitrilotriacetate) provided a survival advantage to endothelial cells. Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. Taken together, these observations suggest that iron may give a survival advantage to endothelial cells and represent a novel mechanism through which iron may contribute to tumorigenesis.
Cell Line↗
Value of standard laboratory tests for the early recognition of group A beta-hemolytic streptococcal necrotizing fasciitis.
The laboratory data for 17 patients with group A beta-hemolytic streptococcal necrotizing fasciitis (GAS NF) were compared with data for 145 patients hospitalized for cellulitis during the same period. Admission values of C-reactive protein and creatine kinase were higher for patients in the group with GAS NF than for patients in the group with cellulitis (P<.001), suggesting that standard laboratory tests may be useful for the early differential diagnosis of GAS NF and cellulitis.
Adolescent↗
ART in HIV-infected couples: has the time come for a change of attitude?
Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication. A growing number of them want to have children. Medical possibilities for preventing contamination of the partners of seropositive men, through assisted reproduction, and of children thanks to antiviral medicines during pregnancy, are summarized. These changes result in ethical considerations which lead the authors to question the conventional systematic medical advice against pregnancy and has encouraged them to assist reproduction for a number of these couples. Today, the balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child has tilted towards medical intervention. It would seem legitimate today to intervene in the most favourable situations rather than see these couples take the risk of spontaneous conception outside health care structures. This implies the need to adapt medical structures (separate laboratory, appropriate procedure, precise protocols). This approach, which is coherent from the scientific point of view, respects both the autonomy of people carrying HIV as well as the essential interests of the child, in being born uninfected, and also has the enormous advantage of allowing access to parenthood without destroying the consistency of the message of prevention of sexual contamination.
Attitude of Health Personnel↗
Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer.
Buruli ulcer, caused by Mycobacterium ulcerans, is characterized by deep and necrotizing skin lesions, mostly on the arms and legs. Together with tuberculosis and leprosy, this mycobacterial disease has become a major health problem in tropical and subtropical regions, particularly in central and western Africa. No specific vaccine is available for Buruli ulcer. There is, however, evidence in the literature that suggests a cross-reactive protective role of the tuberculosis vaccine M. bovis BCG. To identify potential mechanisms for this cross-protection, we identified and characterized the M. ulcerans homologue of the important protective mycobacterial antigen 85 (Ag85A) from BCG. The homologue is well conserved in M. ulcerans, showing 84.1% amino acid sequence identity and 91% conserved residues compared to the sequence from BCG. This antigen was sufficiently conserved to allow cross-reactive protection, as demonstrated by the ability of M. ulcerans- infected mice to exhibit strong cellular immune responses to both BCG and its purified Ag85 complex. To further address the mechanism of cross-reactive protection, we demonstrate here that prior vaccination with either BCG or plasmid DNA encoding BCG Ag85A is capable of significantly reducing the bacterial load in the footpads of M. ulcerans- infected mice, as determined by Ziehl-Neelsen staining and by actual counting of CFU on 7H11 Middlebrook agar. Together, the results reported here support the potential of a cross-protective Ag85-based future vaccine against tuberculosis, Buruli ulcer, and leprosy.
Amino Acid Sequence↗
[Immune deficiencies: diagnosis, management, some perspectives].
Severe primary immunodeficiencies (PID) are rare; their global incidence is comparable to that of childhood leukemia; they include more than 100 different entities. Clinical manifestations are: unusually severe or frequent infections or infections that do not respond to adequate treatment; an increased risk of certain malignancies; sometimes auto-immune manifestations. Delayed diagnosis and management of PID can lead to severe and irreversible complications or to death. PID can become manifest only in the adult; in common variable immune deficiency, the median age at diagnosis is between the 2nd and the 3rd decade of life. PID are often transmitted genetically; recent progresses in molecular biology have allowed more precise and earlier, including antenatal, diagnosis. Molecular treatment of 3 infants with a severe immunodeficiency has recently been achieved in April 2000. Those progresses were mostly based on the study of immunodeficiency databases. We present here the work of a Belgian group specialized in PID; meetings have started in June 1997. This group establishes guidelines for the diagnosis and treatment of PID, adapted to the local situation. The elaboration of a national register of PID is also underway; this has to provide all guaranties of anonymity to patients and families. Such a register already exists at the European level; it has provided the basis for new diagnostic and therapeutic possibilities. The inclusion of Belgian data in this register should allow essential progresses essential for our patients.
Adolescent↗