[Early detection of recurrence of ovarian carcinoma by immunoscintigraphy].
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
P Bernard
Publications and source records attributed to P Bernard.
[Schoenlein-Henoch syndrome in adults and skin infection].
Schoenlein-Henoch purpura is a rare disease in adults clinically characterized by palpable purpura, mainly on the legs, with varying degrees of gastrointestinal, articular and renal involvement. This syndrome is also characterized by IgA-vasculitis and its pathogenesis is still unclear, although it appears frequently after a viral or bacterial infection especially in the ORL sphere. We report here the cases of three adult patients who developed Schoenlein-Henoch purpura shortly after a bacterial infection of the skin, notably by Staphylococcus aureus.
Aged↗
Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes.
In Escherichia coli, the miniF plasmid CcdB protein is responsible for cell death when its action is not prevented by polypeptide CcdA. We report the isolation, localization, sequencing and properties of a bacterial mutant resistant to the cytotoxic activity of the CcdB protein. This mutation is located in the gene encoding the A subunit of topoisomerase II and produces an Arg462----Cys substitution in the amino acid sequence of the GyrA polypeptide. Hence, the mutation was called gyrA462. We show that in the wild-type strain, the CcdB protein promotes plasmid linearization; in the gyrA462 strain, this double-stranded DNA cleavage is suppressed. This indicates that the CcdB protein is responsible for gyrase-mediated double-stranded DNA breakage. CcdB, in the absence of CcdA, induces the SOS pathway. SOS induction is a biological response to DNA-damaging agents. We show that the gyrA462 mutation suppresses this SOS activation, indicating that SOS induction is a consequence of DNA damages promoted by the CcdB protein on gyrase-DNA complexes. In addition, we observe that the CcdBS sensitive phenotype dominates over the resistant phenotype. This is better explained by the conversion, in gyrA+/gyrA462 merodiploid strains, of the wild-type gyrase into a DNA-damaging agent. These results strongly suggest that the CcdB protein, like quinolone antibiotics and a variety of antitumoral drugs, is a DNA topoisomerase II poison. This is the first proteinic poison-antipoison mechanism that has been found to act via the DNA topoisomerase II.
Amino Acid Sequence↗
Quantitation of resistance of leukemic cells to cytosine arabinoside from BrdUrd/DNA bivariate histograms.
The cytotoxicity of ara-C derives from an inhibition of DNA synthesis after incorporation of ara-CTP into DNA. The rate of DNA synthesis can be determined from the amount of bromodeoxy-uridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify the inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrd/DNA. Inhibition was evaluated in ara-C-sensitive and resistant cells after incubation with different doses of ara-C. An index of resistance to ara-C (RI) was expressed as the ratio of the amount of BrdUrd incorporated into S phase cells incubated with ara-C to that incorporated in the absence of ara-C. In the ara-C-sensitive and resistant HL60 cells, a linear relationship between RI and log ara-C concentration was observed. Small numbers of slightly resistant cells in mixtures of ara-C-sensitive and resistant cells could be determined using this method, making it suitable for clinical use to test the resistance of leukemic cells to ara-C.
Bromodeoxyuridine↗
Intercalation of anthracyclines into living cell DNA analyzed by flow cytometry.
Anthracyclines (ANT) are used in the treatment of leukemia and other cancers. These drugs have been shown to intercalate between the strands of DNA. In the present study, we show that the amount of ANT intercalated into DNA can be determined by measuring the fluorescence resonance energy transfer (FRET) between Hoechst 33342 (H33342) and ANT bound to DNA. The transfer efficiency was found to depend on the amount of disposable ANT but was independent of the amount of H33342 bound to DNA over a wide range of H33342 concentrations. The method was adapted for flow cytometric measurement of FRET in whole living cells and was used to evaluate the degree of intercalation of daunorubicin (DAU) and idarubicine (IDA) into DAU-sensitive and DAU-resistant leukemic cell lines. ANT intercalation into DNA was affected by factors which modify the intracytoplasmic concentration of ANT, and it was shown that the action of ANT and the resistance to ANT could not be attributed solely to the intercalative effect of the drugs. The method has advantages over previously described methods and represents a useful complementary tool in studies on the mode of action of ANT and the mechanisms of chemoresistance.
Benzimidazoles↗
Recent advances on the 180-kDa epidermal antigen in autoimmune subepidermal bullous skin diseases.
The blistering skin disease bullous pemphigoid (BP) is an example of how autoantibodies from patients can be used as tools to improve our knowledge of the molecular structure of normal skin. BP autoantibodies bind to the basement membrane zone of normal human skin and usually react with two main epidermal antigens of approximately 230-kDa and 180-kDa. From recent studies, it is now established that the 180-kDa polypeptide is distinct from the 230-kDa BP antigen and is a major component of hemidesmosome. In this article, the recent data regarding the localization and structure of the epidermal 180-kDa BP antigen are reviewed in detail, together with its clinical significance, since it appears to be also a target antigen for pemphigoid (herpes) gestationis and, perhaps, cicatricial pemphigoid autoantibodies.
Autoantigens↗
Erythema elevatum diutinum in a patient with relapsing polychondritis.
A 69-year-old man with a history of relapsing polychondritis developed a widespread cutaneous eruption that was clinically and histologically typical of erythema elevatum diutinum. This eruption was accompanied by a recurrence of arthralgias. The significance of this association between relapsing polychondritis and erythema elevatum diutinum, which has not been previously reported, is discussed.
Aged↗
Localized pretibial pemphigoid and pemphigoid nodularis.
We describe a 75-year-old woman with a chronic, blistering eruption on the left leg whose clinical and immunopathologic features were consistent with a diagnosis of localized pretibial pemphigoid. After a disease-free interval of 5 years she developed a generalized prurigo nodularis-like eruption. Immunofluorescence studies revealed deposition of IgG and C3 along the dermoepidermal junction, and circulating autoantibodies against the dermoepidermal junction were demonstrated. Indirect immunoelectron microscopic examination of saponin-treated skin samples showed deposits of immunoreactants over the intracellular part of the hemidesmosomes. By Western immunoblotting the 230 kd bullous pemphigoid antigen was recognized by circulating autoantibodies. Thus our patient had two unusual clinical variants of bullous pemphigoid: localized pretibial pemphigoid and pemphigoid nodularis.
Aged↗
The major cicatricial pemphigoid antigen is a 180-kD protein that shows immunologic cross-reactivities with the bullous pemphigoid antigen.
Recent studies have shown that sera from patients with cicatricial pemphigoid (CP) contained autoantibodies against epidermal antigens of molecular weight 230 kD and/or 180 kD by immunoblotting, similar to those recognized by bullous pemphigoid (BP) sera. Previous immunoprecipitation studies have shown that BP sera only precipitated the 230-kD antigen. To characterize the CP antigen(s) we tested 10 CP sera, 10 BP sera, and four controls by both immunoprecipitation of radiolabeled cells and immunoblotting of epidermal extracts. For immunoprecipitation, we used 0.5% NP-40 extracts of both normal human keratinocytes and Pam cells. All CP sera precipitated a 180-kD protein that co-migrated with the BP180 antigen precipitated by some individual BP sera. Two of these CP sera also faintly bound a 230-kD protein of similar molecular weight as the major BP230 antigen. CP and BP sera with an immunoblotting pattern of 180 kD immunoprecipitated a co-migrating 180-kD protein. CP sera reacting by immunoblotting with the 230-kD antigen precipitated the 180-kD and/or the 230-kD antigen. In contrast, BP sera reacting with the 230-kD antigen only precipitated this antigen. In further experiments, labeled 0.5% NP-40 extracts from Pam cells were first preabsorbed with a reference BP serum and then immunoprecipitated with CP sera. Under these conditions, CP sera that immunoprecipitated both 180-kD and 230-kD proteins with the standard procedure no longer precipitated these proteins. Our results suggest that a 180-kD protein is the major CP target-antigen that demonstrated immunologic cross-reactivities with the BP180 and the BP230 antigens.
Antigens↗
Roxithromycin versus penicillin in the treatment of erysipelas in adults: a comparative study.
A prospective, randomized, multicentre trial was conducted to evaluate the efficacy and safety of roxithromycin (150 mg b.i.d. orally) and penicillin (2.5 MU x 8 daily intravenously, then 6 MU daily orally) in the treatment of hospitalized adult patients with erysipelas. Seventy-two patients entered the study. Thirty-one patients in the roxithromycin group and 38 patients in the penicillin group completed the trial. The overall efficacy rates (cure without additional antibiotics) were 84% (26/31) in the roxithromycin group and 76% (29/38) in the penicillin group (P = 0.43). No side-effects were observed in the roxithromycin-treated patients whereas rashes occurred in two cases in the penicillin group, leading to exclusion from the study. Oral roxithromycin can thus be considered an effective and well-tolerated treatment for erysipelas in adult hospitalized patients.
Acute Disease↗
A prospective immunofluorescence study of 111 cases of pruritic dermatoses of pregnancy: IgM anti-basement membrane zone antibodies as a novel finding.
Since 1981, all pregnant women presenting to our department with a pruritic dermatosis have been investigated by histological and immunopathological techniques. We recruited 111 patients and performed skin histology in 77, 109 direct immunofluorescence tests (DIF), 74 indirect immunofluorescence tests (IIF) and 15 Western blots (WB). We identified: (i) five typical cases of pemphigoid gestationis (PG) (4.5%), corresponding to an incidence of 1/7000 pregnancies. (ii) Five cases without PG but showing circulating anti-BMZ antibodies of IgM type. With the exception of one case, clinical features were homogeneous--occurrence of erythematous papular and/or urticarial lesions on the trunk, and less often, on the limbs between the 32nd and 38th week of pregnancy. Rapid clearance of lesions within a few days was the rule. Whenever performed, DIF was negative and IIF showed circulating anti-BMZ antibodies of IgM type. Western blot studies were negative in these five cases. (iii) One hundred and one cases with negative immunofluorescence tests, considered to be suffering from polymorphic eruption of pregnancy. Our results show the value of systematic immunopathological investigations in pregnant women presenting with a pruritic dermatosis, and raise the possibility of a new entity, as defined by circulating anti-BMZ antibodies of IgM type.
Adult↗
Determination of plasma delta-aminolaevulinic acid levels. Applications.
Determination of plasma delta-aminolaevulinic acid levels is of interest for the diagnosis of disorders of heme biosynthesis. We describe a reliable method for the determination of this parameter, based on a modification of the original method of Mauzerall and Granick. Analytical criteria are defined and the reference range used, established using data from 40 subjects, was 0.30 to 1.20 mumol/l. Results in patients with porphyria or lead poisoning and in those treated with haemodialysis or anticonvulsants indicate that this determination could be used principally in the diagnosis and management of acute porphyrias and in the early laboratory diagnosis of lead poisoning.
Aminolevulinic Acid↗
Hip surgery skin cellulitis.
Of 583 erysipelas/cellulitis seen in our Department between 1981 and 1991, six (1.04%) were localized to the buttock and hip. Five patients had had a dynamic hip screw implanted for coxarthritis on the side where the skin infection developed. This does not appear to be secondary to superinfection of the surgical wound as the erysipelas/cellulitis occurred weeks (7 to 520) after surgery. The possible surgical compromise of the venous/lymphatic circulation appears to be the causative factor. In all patients, the course was satisfactory upon systemic antibiotic therapy and no recurrence was seen after a mean follow up of 28 months.
Adult↗
Dermo-hypodermal bacterial infections. Current concepts.
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Animals↗
Incomplete stroma formation after allogeneic marrow or autologous blood stem cell transplantation.
Long term and semi-solid culture techniques were used to evaluate the quality of stroma produced by bone marrow from 33 normal subjects and 57 patients (46 allogeneic bone marrow and 11 autologous blood stem cell transplant recipients). Bone marrow from transplant recipients was capable of sustained CFU-GM and nucleated cell production in long term culture. However, only 13% of the marrow investigated developed a complete, confluent stromal layer. These stromal abnormalities were observed in spite of complete hematopoietic reconstitution after transplantation and rarely improved with time. Our results suggest that the hematopoietic microenvironment is very fragile and susceptible to long term damage as a result of chemotherapy and the conditioning regimes used prior to transplantation.
Adolescent↗
[Periarteritis nodosa and preleukemic states].
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Aged↗
Frequency of bullous pemphigoid-like antibodies as detected by western immunoblot analysis in pruritic dermatoses.
BACKGROUND AND DESIGN: Ninety-seven patients suffering from a pruritic dermatosis were screened for the detection of bullous pemphigoid (BP) antibodies (ab) using the Western immunoblot (WB) analysis technique. RESULTS: Twenty-four patients (25%) reacted at least twice with the BP antigen on WB analysis at a 1/10 dilution: seven had typical BP, four had papular BP, 10 had pruritus and prurigo of unknown origin, two had eczema, and one had lichen planus. This corresponds to 13% of BP-type ab in patients who did not fulfill criteria for BP. Therefore, we did the following: (1) tested a control group of 24 subjects; (2) assessed the reproducibility of the WB method by retesting the same serum samples on different epidermal extracts; and (3) estimated the BP ab titer. None of the 24 control subjects had detectable BP ab, and reproducible results were obtained in all groups when serum samples were retested at the 1/10 dilution. Although 86% (6/7) of patients with BP had BP ab titers of 1/100 or greater, only 60% (6/10) of the group with pruritus and prurigo and 33% (1/3) of the group with eczema reached such titers. CONCLUSION: These results indicate that due to its sensitivity, the WB method can detect low titers of BP ab in patients with pruritic dermatoses who did not fulfill criteria for BP, and therefore we question the specificity of this method.
Adult↗
[The value of color Doppler ultrasound in the diagnosis of breast tumors].
A prospective study was performed in 102 patients, including 40 malignant tumors (13 subclinical), to evaluate colour Doppler in breast tumours. All patients had abnormalities that led to their selection for this study. 92 patients had a mammographic examination. 10% of malignant tumours were not detected by mammography. Mammographic abnormalities without any ultrasonographic confirmation were excluded from this series. All the lesions have been proven by cytology or histology. In the assessment of malignancy only one false negative and two false positive results were obtained. The sensitivity and specificity of colour Doppler are both of 97% with radiate vessels beneath the tumour and intratumoral vessels as malignant criteria. This non invasive method should be performed in lesions with tissue ultrasonographic appearances even before fine needle puncture. So it may be possible to select more surgical indications considering an ultrasonographic abnormality atypical, subclinic or post-therapeutic (radiotherapy or surgery).
Adolescent↗