Biomedical subjects

P Roux

Publications and source records attributed to P Roux.

At least 37 records · Page 2Linked to original sources

PubMed2000

Vitamin A status in relation to electroretinographic and electrooculographic findings in HIV infection.

OBJECTIVES: To investigate the electrooculogram (EOG) and an expanded battery of electroretinograms (ERGs) in HIV-infected subjects without retinopathy at two different levels of immunosuppression. Consideration was given to the possible effects of serum levels of vitamin A. METHODS: Two groups of neurologically normal HIV-positive subjects with CD4+ cell counts of <200 (n=17) or >400 (n=19) were contrasted with 20 HIV-negative controls. Rod ERGs, oscillatory potentials and cone ERGs were obtained using ganzfeld stimulation. A sequence of dark- and light-adapted EOG recordings was analyzed to obtain light/dark ratios. The HIV-positive subjects underwent a comprehensive ophthalmologic examination. RESULTS: Intergroup comparisons failed to reveal any significant intergroup differences. Abnormal ERG findings, those exceeding the 98% confidence limits, occurred in 11% (4/36) of the HIV-positive subjects. One of these subjects was hyporetinemic and another had a subnormal retinol level. No subjects had abnormal EOGs. CONCLUSIONS: HIV infection influenced retinal function in 11% of a group of neurologically normal subjects without clinical signs of retinopathy. The profile of electrophysiological findings suggested predominant functional deficits involving middle or inner retinal layers. Vitamin A deficiency and possible vascular changes could account for the observed ERG abnormalities.

Adolescent↗

PubMed2000

Critical activities of Rac1 and Cdc42Hs in skeletal myogenesis: antagonistic effects of JNK and p38 pathways.

The Rho family of GTP-binding proteins plays a critical role in a variety of cellular processes, including cytoskeletal reorganization and activation of kinases such as p38 and C-jun N-terminal kinase (JNK) MAPKs. We report here that dominant negative forms of Rac1 and Cdc42Hs inhibit the expression of the muscle-specific genes myogenin, troponin T, and myosin heavy chain in L6 and C2 myoblasts. Such inhibition correlates with decreased p38 activity. Active RhoA, RhoG, Rac1, and Cdc42Hs also prevent myoblast-to-myotube transition but affect distinct stages: RhoG, Rac1, and Cdc42Hs inhibit the expression of all muscle-specific genes analyzed, whereas active RhoA potentiates their expression but prevents the myoblast fusion process. We further show by two different approaches that the inhibitory effects of active Rac1 and Cdc42Hs are independent of their morphogenic activities. Rather, myogenesis inhibition is mediated by the JNK pathway, which also leads to a cytoplasmic redistribution of Myf5. We propose that although Rho proteins are required for the commitment of myogenesis, they differentially influence this process, positively for RhoA and Rac1/Cdc42Hs through the activation of the SRF and p38 pathways, respectively, and negatively for Rac1/Cdc42Hs through the activation of the JNK pathway.

Animals↗

PubMed2000

Acoustical imaging through a multiple scattering medium using a time-reversal mirror.

Acoustical imaging is based on the ability to focus an acoustic beam inside the zone of interest. This remains an issue through a high-order multiple scattering medium because the electronic delay lines that enable one to focus through a multiple scattering medium are a priori unknown. Using time-reversal principles, we show that images can be obtained through a very disordered medium. Surprisingly, the images are better than those obtained in a homogeneous medium with a classical imaging device.

Acoustics↗

PubMed2000

Time reversal in a waveguide: study of the temporal and spatial focusing

Temporal and spatial focusing properties of time-reversal mirrors (TRMs) are studied in a waveguide. The experiments are done using an ultrasonic TRM in an idealized waveguide. The width of the focal spot, and the spatial and temporal sidelobe levels are experimentally and numerically analyzed with respect to the characteristics of the waveguide-TRM system. An algorithm is developed to compute directly in the time domain the time-reversed field. This algorithm is based on the application of the mirror theorem to both the source and the TRM placed in the waveguide. Because time reversal is a stable and robust process, some of the ultrasonic results can be extended to ocean acoustics. Applications to underwater acoustic transmissions as well as ultrasonic medical imaging are discussed.

Journal Article↗

PubMed2000

Activation of transcription factors NF-kappaB and NF-IL-6 by human immunodeficiency virus type 1 protein R (Vpr) induces interleukin-8 expression.

Human immunodeficiency virus (HIV)-positive individuals express elevated levels of interleukin-8 (IL-8), which is believed to be responsible for some of the clinical manifestations occurring during AIDS. We report here that virion-derived HIV type 1 (HIV-1) protein R (Vpr) increased IL-8 expression in primary T cells and macrophages, as well as in the T-cell line Jurkat, the monocytic cell line U937, and the epithelial cell line A549. Vpr appeared to increase IL-8 expression and IL-8 promoter activity by activating transcription factors NF-kappaB and NF-IL-6. Elevated Vpr was also shown to increase transcription of the NF-kappaB and NF-IL-6 enhancer-containing viral promoters for HIV, cytomegalovirus, and simian virus 40, as well as increase the expression of IL-6 and IL-10 in primary macrophages and in A549 cells, tumor necrosis factor alpha expression in primary T cells, and IL-6 and gamma interferon expression in U937 cells. These results suggest a new role for Vpr in the pathogenesis of HIV infection, namely, the activation of transcription factors NF-IL-6 and NF-kappaB.

CCAAT-Enhancer-Binding Proteins↗

PubMed2000

Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa.

BACKGROUND: Bacteriological confirmation of pulmonary tuberculosis is difficult in infants and young children. In adults and older children, sputum induction has been successfully used; this technique has not been tested in younger children. AIMS: To investigate whether sputum induction can be successfully performed in infants and young children and to determine the utility of induced sputum compared to gastric lavage (GL) for the diagnosis of pulmonary tuberculosis in HIV infected and uninfected children. SUBJECTS AND METHODS: 149 children (median age 9 months) admitted to hospital with acute pneumonia who were known to be HIV infected, suspected to have HIV infection, or required intensive care unit support. Sputum induction was performed on enrollment. Early morning GL was performed after a minimum four hour fast. Induced sputum and stomach contents were stained for acid fast bacilli and cultured for Mycobacterium tuberculosis. RESULTS: Sputum induction was successfully performed in 142 of 149 children. M tuberculosis, cultured in 16 children, grew from induced sputum in 15. GL, performed in 142 children, was positive in nine; in eight of these M tuberculosis also grew from induced sputum. The difference between yields from induced sputum compared to GL was 4.3% (p = 0.08). M tuberculosis was cultured in 10 of 100 HIV infected children compared to six of 42 HIV uninfected children (p = 0.46). CONCLUSION: Sputum induction can be safely and effectively performed in infants and young children. Induced sputum provides a satisfactory and more convenient specimen for bacteriological confirmation of pulmonary tuberculosis in HIV infected and uninfected children.

AIDS-Related Opportunistic Infections↗

PubMed2000

Telemedicine techniques can be used to facilitate the conduct of multicentre trials.

A multicentre randomized controlled trial was established in Pretoria, Bloemfontein and Edendale in South Africa, and coordinated from London. The purpose of the trial was to determine the efficacy of low-dose beta irradiation of glaucoma. Five communication modalities (telephone, fax, e-mail, videoconferencing and face-to-face meetings) were examined in terms of their benefits in a multicentre trial. The eight stages of the multicentre trial examined were: set-up and training, recruitment, standardization, patient management, data transmission, update and data dissemination, clinical follow-up and monitoring, and publication. On four-point Likert scales for rating the usefulness of the communication modalities at each of the eight stages of the trial (from 0 = not useful to 3 = very useful; maximum score 24) the telephone was given a total score of 10, fax 9, e-mail 13, videoconferencing 15 and face-to-face meetings 9. Telemedicine techniques offer considerable benefits in the coordination of multicentre trials by improving data collection, maintaining the efficacy and monitoring of trials, while potentially offering reduced costs in terms of travel and time. The realtime scrutiny of patient records helps to ensure data uniformity and completeness of data collection. Videoconferencing was most useful when considered as one of several communication tools that can be used to improve the effectiveness of a service or process.

Glaucoma↗

PubMed2000

The Cape Town experience with haematopoietic stem cell transplantation: the paediatric programme.

OBJECTIVE: To determine the outcome of children with blood malignancies and bone marrow failure syndromes treated by paediatricians in the context of an adult haematopoietic transplantation programme. DESIGN: Retrospective chart review. SETTING: Hospital wards in a provincial tertiary institution in the Western Cape (Department of Haematology, Groote Schuur Hospital). SUBJECTS: Twenty-eight hospitalised children with haematological malignancies (acute lymphoblastic leukaemia (ALL) N = 4, acute myeloblastic leukaemia (AML) N = 13), or bone marrow failure syndromes (N = 11), who consecutively received autologous or allogeneic marrow grafts from HLA-identical siblings. OUTCOME MEASURES: Children (younger than 18 years) received allogeneic or autologous stem cell transplants. In the former group, two forms of graft-versus-host disease (GVHD) prophylaxis were used. Conditioning with radiation-containing regimens was followed by stem cell product infusion after T-cell depletion (CAMPATH 1, ex vivo immunoglobulin G (IgG); rat anti CD52). Children with malignancies who received unfractionated grafts were myeloablated, mainly with busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Those affected by marrow failure were prepared with cyclophosphamide and antilymphocyte globulin. Median age at time of transplantation was 116 months (range 18-212 months). The main cause of death was disease recurrence (N = 5) and GVHD (N = 3). Twenty-one children survived, 11 of 16 in complete remission (CR) from malignancy. Nine of the eleven patients presenting with marrow failure and 1 patient with severe combined immunodeficiency (SCID) remained disease free at a median follow-up of 934 days (range 70-2,330 days). Significantly longer disease-free (P = 0.03) and overall survival (P = 0.05, Cox Mantel test) was experienced by those who received T-cell-depleted stem cell grafts. CONCLUSIONS: The strategy of T-cell depletion of bone marrow/blood stem cells from HLA-matched siblings for transplantation into children with blood disorders has been successful and cost effective. These favourable results are the consequence of rational co-operation between adult and paediatric transplant physicians.

Adolescent↗

PubMed2000

Burden and cost of inpatient care for HIV-positive paediatric patients--status in the Cape Town metropole during the second week of March 1999. Paediatric HIV Census Group.

OBJECTIVE: To determine the burden of the HIV epidemic on paediatric inpatient facilities in the teaching hospitals of the Cape metropole and tributaries to these hospitals. SETTING: Second- and third-level hospitals. METHOD: During the second week of March 1999 a multicentre collaborative census was performed of all paediatric beds in the teaching hospitals of Cape Town and all facilities draining to and from them. RESULTS: One hundred and six HIV-infected patients were identified from a total of 1,264 beds. Thirty-nine children were in second-level beds or in a long-term residential facility. Fifty-six children were in second-level beds designated for acute care, and occupied 12% of all such beds. Ten children were in beds designated for the care of tuberculosis. Thirty-two (56%) of the acute admissions were for gastro-enteritis, and 13 (23%) were for pneumonia. In 10 children (18% of all admissions) recognised complications of HIV infection were direct causes of admission. For 29 children (35% of all admissions) the current admission was the first; the remainder had had a mean of 2.4 previous admissions. Fourteen children (25%) had received oxygen, and 26 (46%) had received intravenous therapy. Mean lifetime hospitalisation cost per infected child was calculated to be R19,712. The projected cost of a local initiative to reduce mother-to-child transmission is between R8,326 and R10,806 per vertical infection prevented. CONCLUSION: The inpatient burden of HIV-infected children in Cape Town reflects an early stage of the epidemic. Compared with projected lifetime hospitalisation cost for infected children, an intervention to reduce vertical transmission cost would be cost effective.

Bed Occupancy↗

PubMed1999

Simultaneous determination of pyrimidine or purine deoxyribonucleoside triphosphates using a polymerase assay.

In this paper, we describe an improved enzymatic assay for the determination of deoxyribonucleoside triphosphates (dNTPs). This is based on the elongation of 32P 5'-end-labeled oligonucleotide primers annealed to complementary oligonucleotide templates. Incorporation within the primer/template (p/t) was catalyzed by the Klenow fragment of Escherichia coli DNA polymerase I under conditions where the concentration of the dNTP to be analyzed is limiting. Using a combination of two different sized p/t pairs, dCTP and dTTP (or dATP and dGTP) were assayed together. Since the elongated products were clearly separated after electrophoresis on a denaturing 10% polyacrylamide gel, the two dNTPs could be quantified in a single lane. This method allows for the first time the simultaneous determination of two pyrimidine or two purine deoxyribonucleoside triphosphates. Consequently, a large number of biological samples can be tested in a single experiment. The high sensitivity of this method enables the quantification of low concentrations of dNTPs, such as those found in resting nondividing cells. Furthermore, this new protocol is well suited for the determination of dNTPs in cells treated with the antiretroviral ddI, since the Klenow fragment has a low affinity for ddATP, the active form of ddI.

Anti-HIV Agents↗

PubMed1999

Comparison of the kinetics of S-S bond, secondary structure, and active site formation during refolding of reduced denatured hen egg white lysozyme.

To investigate the role of some tertiary interactions, the disulfide bonds, in the early stages of refolding of hen lysozyme, we report the kinetics of reoxidation of denatured and reduced lysozyme under the same refolding conditions as those previously used to investigate the kinetics of regain of its circular dichroism (CD), fluorescence, and activity. At different stages of the refolding, the oxidation of the protein was blocked by alkylation of the free cysteines with iodoacetamide and the various oxidation states present in the samples were identified by electrospray-mass spectrometry. Thus, it was possible to monitor the appearance and/or disappearance of the species with 0 to 4 disulfide bonds. Using a simulation program, these kinetics were compared with those of regain of far-UV CD, fluorescence, and enzymatic activity and were discussed in terms of a refined model for the refolding of reduced hen egg white lysozyme.

Animals↗

PubMed1999

AIDS-related Pneumocystis carinii pneumonia in the era of adjunctive steroids: implication of BAL neutrophilia.

Factors predictive of mortality in patients with AIDS and Pneumocystis carinii pneumonia (PCP) were identified before the introduction of adjunctive steroids, but they have not been reevaluated since. Because PCP still occurs in AIDS, remaining fatal in some cases, we conducted a multivariate analysis of factors predicting mortality in patients with HIV-positive PCP managed from 1990 to 1995, i.e., after the consensus conference on the use of adjunctive steroids. The predictive value of clinical, laboratory, and bronchoalveolar lavage (BAL) data at admission and during the course of PCP was studied retrospectively using multivariate methods, in 144 patients with AIDS. Overall mortality was 21.5%. The univariate analysis identified seven factors predictive of 90-d mortality: Pa(O(2)) on room air < 60 mm Hg, lactate dehydrogenase > 1,000 IU, albuminemia < 30 g/L, BAL neutrophilia > 10%, nosocomial infection, pneumothorax, and a need for mechanical ventilation. Four of these factors were independently associated with 90-d mortality in the multivariate analysis; among them, two were evaluable at admission, namely, Pa(O(2)) < 60 mm Hg on room air and BAL neutrophilia > 10%, and two during hospitalization, namely, the development of pneumothorax and a need for mechanical ventilation. Moreover, BAL neutrophilia was correlated to occurrence of pneumothorax and a need for mechanical ventilation. In the era of adjunctive steroid use, AIDS-related PCP remains fairly common. Two independent factors evaluable at admission, Pa(O(2)) on room air and BAL neutrophilia, are predictive of death.

AIDS-Related Opportunistic Infections↗

PubMed1999

[PTEN: a tumor suppressor with original properties].

A large effort has been made to understand the intracellular function of a novel tumor-suppressor gene, PTEN, recently identified in the 10q23 chromosome region that is often altered in human tumors. PTEN is a multifunctional protein endowed with a phosphatase activity capable of dephosphorylating not only proteins, at tyrosine, serine or threonine residues, but also phospholipids of the phosphatidylinositol pathway. Its protein phosphatase activity allows it to inhibit the Ras/Mek/Erk cascade, as well as FAK, the focal adhesion kinase, and thus to affect the interactions of cells with intracellular matrix which are important in the mechanism of invasion. Its lipid phosphatase activity blocks the PI3K/Akt pathway, provokes an arrest in G1 of the cell cycle and an increased sensitivity to apoptosis. PTEN therefore acts simultaneously on the morphology and the proliferation of tumoral cells and has thus been attributed a major role in tumor suppression.

Apoptosis↗

PubMed1999

Osteoarthritis caused by Neocosmospora vasinfecta.

We report the case of a patient who developed an ankle osteoarthritis due to the Ascomycete Neocosmospora vasinfecta, following accidental multiple trauma to his legs in whilst in Africa. Antifungal susceptibility testing was performed. Despite a low amphotericin B minimal inhibitory concentration, parenteral antifungal therapy failed and amputation was required to resolve the osteoarthritis. Possible reasons for the failure of this antifungal treatment are examined.

Adult↗

PubMed1998

Increased apoptosis, changes in intracellular Ca2+, and functional alterations in lymphocytes and macrophages after in vitro exposure to static magnetic field.

Electromagnetic-related alteration of cellular functions is well documented for extremely low-frequency low-energy pulsing electromagnetic fields (ELF-EMF). In this study we examined the in vitro effects of static magnetic fields (SMF) on the cellular immune parameters of the C57BI/6 murine macrophages, spleen lymphocytes, and thymic cells. The cells were exposed in vitro for 24 h at 37 degrees C, 5% CO2, to 250-1500 G SMF. Exposure to the SMF resulted in the decreased phagocytic uptake of fluorescent latex microspheres, which was accompanied by an increased intracellular Ca2+ level in macrophages. Exposure to SMF decreased mitogenic responses in lymphocytes, as determined by incorporation of [3H]thymidine into the cells. This was associated with the increased Ca2+ influx in concanavalin A-stimulated lymphocytes. Furthermore, exposure to SMF produced markedly increased apoptosis of thymic cells, as determined by flow cytometry. Overall, in vitro exposure of immunocompetent cells to 250-1500 G SMF altered several functional parameters of C57BI/6 murine macrophages, thymocytes, and spleen lymphocytes.

Animals↗

PubMed1998

The mitochondrial ADP/ATP carrier: structural, physiological and pathological aspects.

Under the conditions of oxidative phosphorylation, the mitochondrial ADP/ATP carrier catalyses the one to one exchange of cytosolic ADP against matrix ATP across the inner mitochondrial membrane. The ADP/ATP transport system can be blocked very specifically by two families of inhibitors: atractyloside (ATR) and carboxyatractyloside (CATR) on one hand, and bongkrekic acid (BA) and isobongkrekic acid (isoBA) on the other hand. It is well established that these inhibitors recognise two different conformations of the carrier protein, the CATR- and BA-conformations, which exhibit different chemical, immunochemical and enzymatic reactivities. The reversible transition of the ADP/ATP carrier between the two conformations was studied by fluorometric techniques. This transconversion, which is only triggered by transportable nucleotides, is probably the same as that which occurs during the functioning of ADP/ATP transport system. The fluorometric approach, using the tryptophanyl residues of the yeast carrier as intrinsic fluorescence probes, was combined to a mutagenesis approach to elucidate the ADP/ATP transport mechanism at the molecular level. Finally, recent reports that myopathies might result from defect in ADP/ATP transport led us to develop a method to quantify the carrier protein in muscular biopsies.

Adenosine Diphosphate↗

PubMed1998

[The sitting position in neurosurgery: the viewpoint of the anesthetist].

The sitting position can be used safely in neurosurgery, if meticulous attention is given to the positioning and the monitoring of the patient during surgery. Venous air embolism remains the most frequent complication. Hypotension is the second complication. A rigorous patient selection of patients, the experience of the anesthesiologist and the neurosurgeon remain the main factors for the choice of the sitting position.

Anesthesia↗

PubMed1998

RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs.

RhoG is a member of the Rho family of GTPases that shares 72% and 62% sequence identity with Rac1 and Cdc42Hs, respectively. We have expressed mutant RhoG proteins fused to the green fluorescent protein and analyzed subsequent changes in cell surface morphology and modifications of cytoskeletal structures. In rat and mouse fibroblasts, green fluorescent protein chimera and endogenous RhoG proteins colocalize according to a tubular cytoplasmic pattern, with perinuclear accumulation and local concentration at the plasma membrane. Constitutively active RhoG proteins produce morphological and cytoskeletal changes similar to those elicited by a simultaneous activation of Rac1 and Cdc42Hs, i.e., the formation of ruffles, lamellipodia, filopodia, and partial loss of stress fibers. In addition, RhoG and Cdc42Hs promote the formation of microvilli at the cell apical membrane. RhoG-dependent events are not mediated through a direct interaction with Rac1 and Cdc42Hs targets such as PAK-1, POR1, or WASP proteins but require endogenous Rac1 and Cdc42Hs activities: coexpression of a dominant negative Rac1 impairs membrane ruffling and lamellipodia but not filopodia or microvilli formation. Conversely, coexpression of a dominant negative Cdc42Hs only blocks microvilli and filopodia, but not membrane ruffling and lamellipodia. Microtubule depolymerization upon nocodazole treatment leads to a loss of RhoG protein from the cell periphery associated with a reversal of the RhoG phenotype, whereas PDGF or bradykinin stimulation of nocodazole-treated cells could still promote Rac1- and Cdc42Hs-dependent cytoskeletal reorganization. Therefore, our data demonstrate that RhoG controls a pathway that requires the microtubule network and activates Rac1 and Cdc42Hs independently of their growth factor signaling pathways.

3T3 Cells↗