Reversal of multiple drug resistance by tolyporphin, a novel cyanobacterial natural product.

The effects of a novel porphyrin, tolyporphin, on P-glycoprotein-mediated multiple drug resistance in human ovarian and breast cell lines were characterized. Compared with parental SKOV3 and MCF-7 cells, the P-glycoprotein-overexpressing sublines SKVLB1 and MCF-7/ADR were 5- and 1.3-fold less sensitive to the cytotoxic effects of tolyporphin. Subtoxic doses of tolyporphin increased the sensitivity of the SKVLB1 and MCF-7/ADR cells to P-glycoprotein-transported drugs, but did not increase the antiproliferative effects of nontransported drugs. Tolyporphin also enhanced the accumulation of [3H]-vinblastine in SKVLB1 and MCF-7/ADR cells at doses approximately 10-fold lower than those required for similar responses to verapamil. In contrast, tolyporphin did not affect drug accumulation in SKOV3 or MCF-7 cells. Tolyporphin reduced [3H]-vinblastine efflux from SKVLB1 cells, reduced [3H]-vinblastine binding to membranes from SKVLB1 cells, and blocked the ability of [3H]-azidopine to photoaffinity-label P-glycoprotein in these membranes. These results indicate that tolyporphin binds to P-glycoprotein and inhibits the transport of cytotoxic natural product drugs. This novel natural product, and related compounds, may be useful for the reversal of multiple drug resistance and for further definition of the drug binding site(s) of P-glycoprotein.

Inhibition of reverse transcriptase activity by extracts of cultured blue-green algae (cyanophyta).

Lipophilic and hydrophilic extracts of over 900 strains of cultured blue-green algae (cyanophyta) were examined in vitro for their ability to inhibit the reverse transcriptases (RT) of avian myeloblastosis virus (AMV) and human immunodeficiency virus, type 1 (HIV-1). Eighteen (2.0%) aqueous extracts showed activity against AMV and HIV RTs. The maximal level of RT inhibition achieved by some of the active extracts was equivalent to that measured for 3'-azido-2',3'-di-deoxythymidine (AZT) at 668 ng/ml. Examination of partially purified fractions prepared by C18 column chromatography demonstrated that the RT inhibition observed could not be attributed entirely to the degradation of transcript DNA, template RNA, or enzyme protein in the reaction mixture. Thus, these results indicate that cultured blue-green algae may represent a novel source of compounds that inhibit RT activity, including that of HIV-1.

Antifungal cyclic peptides from the terrestrial blue-green alga Anabaena laxa. I. Isolation and biological properties.

Laxaphycins are responsible for the antifungal and cytotoxic activity of crude ethanolic extracts from the cultured blue-green alga Anabaena laxa. These cyclic peptides exhibit an unusual biological synergism when tested for antifungal or cytotoxic effects. The isolation procedure for the peptides, their characterization and biological activities are described here along with experiments demonstrating synergism between the two major laxaphycins.

Isolation, NMR studies, and biological activities of onopordopicrin from Centaurea sonchifolia.

A sesquiterpene lactone, onopordopicrin [1], has been isolated from Centaurea sonchifolia. Its structure was established by 2D nmr (1H-1H and 13C-1H correlations), and the conformation in CHCl3 was examined by nOe studies. Cytotoxic, antibacterial, and antifungal activities are reported.

Cytotoxic, fungicidal nucleosides from blue green algae belonging to the Scytonemataceae.

Tubercidin, toyocamycin, and the corresponding 5'-alpha-D-glucopyranose derivatives of the nucleosides are frequently responsible for much of the cytotoxicity and antimycotic activity associated with extracts of cultured cyanophytes belonging to the family Scytonemataceae. The 5'-alpha-D-glucopyranoses of tubercidin and toyocamycin, for example, are the major cytotoxic and fungicidal nucleosides in Fijian Plectonema radiosum and Hawaiian Tolypothrix tenuis, respectively.

[Lyme disease. Clinical, biological and developmental aspects. 29 cases in the Orléans region]. / Maladie de Lyme. Aspects cliniques, biologiques et évolutifs. 29 cas en région orléanaise.

The description of Lyme's disease (LD) in 3 stages (like syphilis), has now become classical. 29 cases of LD, between June 1981 and November 1986, have been recorded at the Hospital in Orleans. The first twelve patients that were clinically diagnosed before the serology was introduced in France, have been recalled in order to search for possible late forms and assay their antibody level of anti-Borrelia burgdorferi. The preponderance of neurological forms (22 cases) and the scarcity of peripheral and/or arthralgic arthritis (8 cases) are emphasized by this study. Radiculalgias (18 cases in 22 meningo-radiculitis), especially in the lower extremities (14 cases), required hospitalization in rheumatology in 21 instances. Spinal algias (16 cases), were only isolated, at the time of hospitalization, in one case. The intense and nocturnal nature of the radiculalgias and spinal algias was noted in 17 of 18 cases, and 16 of 16 cases, respectively. Two atrio-ventricular blocks required hospitalization in cardiology. The long-term follow-up (3 to 5 years) of 12 patients revealed only 2 cases of severe asthenia and swelling at the puncture site in one case. There were no entesopathies nor chronic arthritis. The search for anti-Borrelia burgdorferi antibodies in the serum, was positive 24 times in 28. In the 4 cases where the serology was negative, the samplings were taken after a follow-up of more than three years in 3 instances.(ABSTRACT TRUNCATED AT 250 WORDS)

[Geographic distribution of multiple myeloma in the Loiret region. 10-year retrospective epidemiological survey]. / Répartition géographique du myélome multiple dans le Loiret. Enquête épidémiologique rétrospective sur dix ans.

Suspecting the presence of a myeloma focus in a forest area of the Loiret department, we have undertaken a retrospective epidemiological survey on this disease. Three surveys were conducted, between 1972 and 1982: the first one among general practitioners; the second one was carried out from immuno-electrophoreses performed at the University Hospital in Orleans; the third survey was carried out from reports on the medical causes of deaths. The mean number of myelomas in the Loiret (0.029 p. cent) is comparable to the national mean (0.025 p. cent), with a sex ratio of 47.09 p. cent of men, also quite similar to the national sex ratio (46.7 p. cent). The different districts were classified according to the percentages observed in "neutral areas" (mean plus or minus a typical variation), "cold areas" (between one and two typical variations below the mean) and "hot areas" (between one and two typical variations above the mean). These results do not permit to ascertain the existence of a geographical focus of myelomas in Loiret but require a more in-depth study of "hot areas".

[Value of the measurement of intra-articular lactates. Contribution to the diagnosis of septic arthritis. Interpretation of 370 evaluations]. / Intérêt de la mesure des lactates intra-articulaires. Apport au diagnostic des arthrites septiques. Interprétation de 370 évaluations.

This retrospective study interprets the results of 370 evaluations of the lactate level of joint fluid. 5 groups were established: joint fluid from cases of mechanical (114) and microcrystalline (67) joint diseases, from inflammatory arthritis (149) and from septic arthritis (40). There was a significant difference between the lactate level in fluid from septic joints and that in the other groups. However, there was no significant difference between the rheumatoid joint fluid and the septic joint fluid. The increased level of intra-articular lactate can therefore be considered to be an argument in favour of the diagnosis of septic arthritis, but there is a certain rate of false positives (particularly in the case of rheumatoid arthritis) and false negatives, which require a very careful interpretation of the test. In cases of inflammatory arthritis with a cell count of more than 10,000 per mm3, there is a correlation between the white cell count and the lactate level. This relation is not observed in the case of septic arthritis. The authors did not detect any difference in the levels of intra-articular lactate according to the nature of the infecting organism. They studied 4 specimens of joint fluid from gonococcal arthritis and the levels of lactate were similar to those of other types of septic arthritis.

[Chronic arthritis in palmo-plantar pustulosis. Bacterid of Andrews]. / Arthrites chroniques des pustuloses palmo-plantaires. Bactérides d'Andrews.

Report of a 30 years old man story pustulosis palmaris et plantaris, spondylodiscitis L5-S1, right sterno-clavicular arthritis, right sacro-iliitis, and pubic symphysitis. Multiple bacteriologic investigations did not discover any infectious articular process. Histologic articular findings were inflammatory pattern, non steroid anti-inflammatory drugs corrected the arthritis. Anterior thoracic arthropathies are quasi-constant. Inflammatory spondylodiscitis are frequent, while sacro-iliac involvement is infrequent, this pattern distinguishing pustular arthro-osteitis from classic pelvispondylitis. Radiologic lesions are peculiar by predominance on one articular side at each site. Nosology is discussed. Slow infection by non virulent germs has been suspected , but seems improbable. This affection seems close seronegative spondylo-arthropathies and reactive arthritis, like acne conglobata arthritis for instance. Usual absence of HLA-B27 antigen must be noted.

Cell-mediated immune response to respiratory syncytial virus infection in owl monkeys.

The suitability of owl monkeys as experimental models to study the cellular immune response to respiratory syncytial virus (RSV) infection was examined. Seronegative owl monkeys inoculated intranasally with RSV shed large quantities of virus and developed clinically evident upper respiratory disease. RSV infected monkeys had significant lymphoproliferative responses to RSV antigen by 4 weeks post-infection. In contrast, no positive blastogenic responses were elicited during the acute phase of illness. An in vitro 51Cr release assay was developed to study owl monkey antibody-dependent cellular cytoxicity (ADCC) against RSV infected Hep-2 cells. Peripheral blood mononuclear cells from owl monkeys in the presence of RSV specific antibody caused lysis of RSV infected target cells. The effector cell for ADCC was found to be non-adherent to plastic. The owl monkey RSV ADCC system was found to closely parallel RSV specific ADCC observed with human effector cells. In addition, it was found that heterologous matches of human effector cells with monkey sera and monkey effector cells with human sera were equally efficient in mediating RSV specific ADCC. These studies demonstrate the value of the owl monkey as a model to study the pathogenesis or RSV infections.