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Biomedical subjects

J Roux

Publications and source records attributed to J Roux.

At least 19 recordsLinked to original sources

[Leprosy serology: current status and perspectives].

The different serological tests used for leprosy are firstly the methods for the detection of antibodies (anti-PGL1, 35kD, 36kD, LAM), and secondly, the tests to detect the PGL1 antigen from the serum or urine. The antibody detection tests have a good but insufficient specificity for the diagnosis of leprosy patients and their sensitivity is generally high for the multibacillary patients but low for the paucibacillary patients. Their positive predictive value for the diagnosis of patients in a population are very low: 2.1% for the anti-PGL1 ELISA when the prevalence is 1/1000. For the early diagnosis of patients and the follow up of high risk populations, these tests are not cost effective: the number of patients detected in these populations is 10 fold lower than in the general population and the relative risks for developing the disease are not different among seropositive and among seronegative groups. In treated multibacillary patients, the IgM anti-PGL1 level decreases in correlation with the decrease of the bacillary index. For the diagnosis of M. leprae infection in a population, there was no correlation between the anti-PGL1 seroprevalence and the prevalence of the disease. Concerning the PGL1 antigen detection tests, they are specific and sensitive for the diagnosis of multibacillary patients but they cannot be used in routine for technical reasons. In conclusion and to date, the usefulness of serological tests in a leprosy control programme is quite questionable.

Enzyme-Linked Immunosorbent Assay

[Rift Valley fever in Madagascar in 1991. Sero-epidemiological studies in cattle].

Rift Valley fever (RVF) virus was detected for the first time in Madagascar in 1979, but without any impact on human and animal populations. However, in 1990 and 1991, several outbreaks with massive cattle abortions were described. Since that period, seroepidemiological surveys have been conducted on the East coast and in the highlands (outbreak areas), in the high cattle density regions, and in the national slaughter house in Antananarivo. A high RVF IgM antibody prevalence was detected in the outbreak areas during the epizootics. This IgM prevalence thereafter decreased and was followed by an IgG high prevalence in all tested regions. Hypotheses on the occurrence of the virus in Madagascar, outbreak origins and virus circulation on the island are discussed.

Animals

[The plague: disease and vaccine?].

Plague has existed in Madagascar since 1896, with epidemic control achieved by GIRARD with an EV vaccine in 1937. Plague persists in Madagascar, however, due to the large animal reservoir. With a predilection for nodal tissues, Yersinia pestis is a virulent bacteria that is potent inducer of antibody synthesis. Immunity mechanisms stimulated by infection were studied: 1. In human by immunoenzymatic methods 2. In mice by seroprotection and vaccinating tests. Induced immunity for people in endemic and endemic-epidemic areas, is significant, affecting approximately 70% of these populations. In non endemic areas, immunity is found in only 33% of the population, perhaps this explains the persistence of epidemic? In all cases, this immunity is a quick onset (6 days), is persistent (> 2 years), and has demonstrable serious recognition of YOP (Yersinia Outer Proteins) by Western Blot method. Human antibodies were shown to be protective for mice. Animals vaccinated by YOP were protected equally well, when compared to animals infected with Yersinia pestis and subsequently treated with antibiotics. Finally, YOP aerosols were also shown to induce antibodies. In conclusion, plague is a vaccinatable bacterial disease and YOP can be used as an animal vaccine to permit plague control in the rat reservoir.

Aerosols

[Cysticercosis in Madagascar: diagnostic and therapeutic improvement].

Human cysticercosis is linked to infection by the larval stage of Taenia solium: Cysticercus cellulosae and was identified in Madagascar since 1901. Neurocysticercosis constitute, when parasite is localized in cerebral vesicles, a disease with important neurologic symptoms: epilepsia, spasms... This disease would be diagnosed before parasite calcification and this diagnosis permit Praziquantel treatment indication, with good results in many cases. We have developed cysticercosis diagnosis permitting: stage definition of the disease: Elisa and Western Blot tests, therapeutic following by enzyme immunoassay capture of serum cysticercosis antigens. We have observed: disease prevalence of 18% proving high rate of circulating parasite, in the countries studies, significative variation of circulating antigens and/or antibodies, one month after one or two Praziquantel treatment, in 82% of 130 patients. This disease seems to be important in Madagascar in neurologic syndromes, but the solution of this problem would result in prophylactic and concerted actions by public health means.

Adolescent

[Stability and chemosensitivity of Plasmodium falciparum to chloroquine in 1990 and 1991 in Ankazobe, a village in high plateau Madagascar].

The in vivo and in vitro response of Plasmodium falciparum to chloroquine was conducted in Ankazobe, a village located in the high plateau area. These studies confirmed the low level of chloroquine-resistance. The in vivo data indicate the absence of increase resistance during the 2 years study. Chloroquine is still the drug of choice for the treatment of malaria attack in this area.

Animals

In vivo footprinting of rat TAT gene: dynamic interplay between the glucocorticoid receptor and a liver-specific factor.

HNF5, a liver-specific DNA-binding protein, interacts with DNA in a manner that allows DNAase I cleavage in the middle of its recognition sequence. Using this property we have identified in vivo HNF5 bound to its sites within two glucocorticoid-responsive units of the rat tyrosine aminotransferase (TAT) gene. One HNF5-binding site is also a glucocorticoid receptor-binding site; glucocorticoid-dependent HNF5 binding could be detected at this site even though it is incompatible with glucocorticoid receptor binding. HNF5 binds within 10 min of hormone addition, indicating that it participates in transcriptional activation. In the TAT gene glucocorticoid-dependent HNF5 binding occurs where there is glucocorticoid-dependent disruption of nucleosomal structure; constitutive binding occurs in constitutively disrupted regions. These results suggest a hit-and-run mechanism of transcriptional activation by glucocorticoid receptor: the activated receptor binds its target sequence, modifies local chromatin structure, then leaves its site accessible to another factor.

Animals

Cell-type specific activity of two glucocorticoid responsive units of rat tyrosine aminotransferase gene is associated with multiple binding sites for C/EBP and a novel liver-specific nuclear factor.

The structures of two remote glucocorticoid responsive units (GRUs) that cooperatively interact to promote cell-type specific glucocorticoid induction of rat tyrosine aminotransferase gene expression have been analyzed. DNAase I footprinting and gel mobility shift analyses reveal a complex array of contiguous and overlapping sites for cell type-specific DNA binding proteins. Apart from the glucocorticoid receptor, two liver-specific nuclear factors possess multiple binding sites in each of these GRUs: C/EBP and a newly identified liver-specific factor: HNF5. C/EBP possesses four binding sites in each GRU; a DNA-binding protein with similar binding specificity has been identified in fibroblasts; this protein could be related to AP-3. HNF5 possesses two binding sites in one GRU and four in the other. There are also HNF5 binding sites in numerous regulatory regions of other liver-specific genes. The interaction of HNF5 with DNA gives a characteristic DNAase I footprint with hypersensitive sites in the middle of the recognition sequence. Some of the C/EBP and HNF5 binding sites overlap in a conserved arrangement.

Animals

Dengue surveillance in French Polynesia: an attempt to use the excess number of laboratory requests for confirmation of dengue diagnosis as an indicator of dengue activity.

The excess number of weekly laboratory requests for confirmation of dengue diagnosis over the expected number of requests forecasted by the modified Serfling method is proposed for the surveillance of dengue in French Polynesia, in addition to conventional methods. Retrospective analysis of the seasonal curves of dengue activity related to the number of laboratory requests is described for the years 1982-1987 where dengue type 4 was the only active flavivirus at the time when the forecast was initiated. By using past epidemic data, the probability of failing to recognize an increase in excess of requests as possibly epidemic was of 13.2% and 5.8%, respectively, when the criterion for epidemic increase was set respectively at 2 and 3 successive weeks during which the epidemic threshold is exceeded. A weekly surveillance was set up prospectively for 1988 using these criteria.

Clinical Laboratory Techniques

Evaluation of gelatin particle agglutination assay for the detection of anti-PGLI antibodies. Comparison with ELISA method and applicability on a large scale study using blood collected on filter paper.

Given the technical difficulties of the ELISA method, a gelatin particle agglutination test (MLPA) has been developed recently for the detection of anti-PGLI antibodies. The purpose of this study was to compare these 2 tests. MLPA was found to be less specific than ELISA (91% versus 98%, chi 2 = 66.8, p less than 0.001). The sensitivity of both tests was of 95% for the diagnosis of multibacillary patients. In the case of paucibacillary patients. MLPA was found to be less sensitive than ELISA (21% versus 35%, chi 2 = 6.98, p greater than 0.01). The agreement between the 2 tests for a positive or a negative result was satisfying (85% to 100%), except for the weakly seropositive individuals (71%). The correlation between OD obtained with ELISA and antibody titre obtained with MLPA was statistically significant (r = 0.70, p less than 0.001). Conversely to ELISA, MLPA was not applicable on blood samples absorbed on filter paper without a serious loss of sensitivity. In conclusion, this study demonstrated that the MLPA test can only reliably detect anti-PGLI antibodies in multibacillary cases.

Agglutination Tests

COR3224--a new antidepressant: pharmacokinetics and metabolism in rat.

COR3224 is a new 2-amino-2 oxazoline derivative with antidepressant properties. The distribution, excretion and metabolism of radiochemically labelled 14C-COR3224 has been investigated in the rat after intravenous injection. The compound was widely distributed and rapidly excreted. Hydroxylation and sulphate conjugation are involved in the COR3224 elimination.

Animals

[Respective importance of vertical and horizontal transmission of hepatitis B in the Australian archipelago (French Polynesia). Preliminary results of the vaccination of newborns].

A seroepidemiological survey of hepatitis B was conducted in 1988 in the Austral archipelago (French Polynesia) in a randomly selected sample of 957 persons, has showed an infection rate (at least one positive marker) with HBV of 64.1% for the entire archipelago. Among women of child-bearing age, HBs Ag carriage rate was 11.45% of whom 19.1% were so HBe Ag carriers. Among infants HBs Ag carriage rate was 2.1% and among juveniles it was 10.6%. In this area horizontal transmission of HBV is essential. An immunization program was implemented in August 1988 using a recombinant vaccine (GenHevac BTM). At one year of the program, 97% of the children had received at least one dose of vaccine, 90% had HBs-antibodies titer higher than 10 mUI/ml, 96% had seroconverted for at least one of the two antibodies (anti-HBs and/or anti-preS2) and any of them was neither HBs Ag carrier nor anti-HBc IgM antibodies carrier. Finally, among 7 neonates whose mother were positive for both HBs Ag and HBe Ag, 6 were immunes and the last one, aged of 1 month (one dose received only), was not HBs Ag carrier. These preliminary results show that vaccination with GenHevac BTM to be immunogenic and effective in field conditions.

Adolescent

Relationships between PGL-1 antigen in serum, tissue and viability of Mycobacterium leprae as determined by mouse footpad assay in multibacillary patients during short-term clinical trial.

In connection with a 56-day controlled clinical trial for comparing the therapeutic effects between pefloxacin and ofloxacin in 21 lepromatous patients, we have studied the relationships between PGL-1 antigen level in serum and in skin and serum PGL-1 antibody titre on the one hand, and the viability of Mycobacterium leprae, as measured by serial mouse footpad inoculations, and other bactericidal parameters on the other. Before and during treatment, significant correlation was found between serum PGL-1 level and the morphological index (MI), and with the number of viable organisms per mg skin tissue. However, neither serum PGL-1 antibody titre nor skin PGL-1 antigen level showed significant change during the 56-day trial. Because the reduction of serum PGL-1 level was well correlated but less pronounced as compared with the evolution of viable organisms during treatment, the serum PGL-1 antigen assay may be useful as an early indicator of response to chemotherapy in short-term clinical trial, but it is unlikely to replace mouse footpad inoculation for the evaluation of viability of M. leprae.

Animals

[Epidemiology of primary liver cancer in French Polynesia].

Thirty-one cases of primary liver cancer recorded since 1980 to 1988 in French Polynesia are studied. Four risk factors are brought to the fore: male, more than 50 years old, birth in Austral archipelago and in this case AgHBs carriage. The relative risk for birth in Austral archipelago reach to 9.23. The relative risk for AgHBs carriers from this archipelago reach to 42.7. Costs of primary liver cancer and to immunization against hepatitis B virus are compared. Authors suggest to start an immunization program.

Adenoma, Bile Duct

[The detection of IgM antibodies to phenolglycolipid I for serodiagnosis of Hansen's disease and monitoring the contact population in Polynesia. Five year evaluation].

This study was conducted to assess the usefulness of IgM anti-PGLI antibody test, for the diagnosis of leprosy and of the subclinical infection among contact population. Even if the specificity (97.7%), sensitivity (98% for the multibacillary, but 36% for the paucibacillary) and efficiency (97.7%) of the test for the diagnosis of patients are good, its positive predictive value which is the proportion of true patients among the seropositive subjects detected in the population was very low (1.17% in Polynesia), because of the very low prevalence of leprosy. For the diagnosis of the subclinical infection, our experience based on the follow up of a population of 1,123 contacts, showed that such a control program would have low feasibility and low cost-effectiveness. After 5 years, the proportion of individuals developing the disease was not different among the seropositive than among the seronegative subjects. Finally, only 17.5% of the new cases of leprosy detected, were issued from the contact population followed. In conclusion and in a practical point of view, although this test may contribute to the diagnosis of patients, it is not likely useful neither for the diagnosis nor for the prognosis of leprosy in a population.

Antibodies, Bacterial

Two remote glucocorticoid responsive units interact cooperatively to promote glucocorticoid induction of rat tyrosine aminotransferase gene expression.

Tyrosine aminotransferase (TAT) gene transcription is specifically activated by glucocorticoid hormones in liver cells. This regulation involves a glucocorticoid responsive region located 2,500 bases upstream from the transcription start site of the rate gene. By transient transfection of TAT-CAT fusion genes into a rat hepatoma cell line expressing the TAT gene we found that this region promotes only 30% of the glucocorticoid stimulation. We have identified a new cis-acting region far upstream (-5,400) from the transcription start site that is essential to achieve the physiological level of glucocorticoid stimulation of endogenous TAT gene expression. This region corresponds to a tissue-specific DNAse I hypersensitive site which is constitutive despite the fact it possesses a glucocorticoid receptor binding site. It is by itself almost inactive on a promoter but it cooperatively enhances the action of the proximal glucocorticoid responsive region. Its activity requires both the glucocorticoid receptor binding site and its flanking sequences.

Animals