Biomedical subjects
Publications and source records attributed to B Dupont.
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Sensitivity to the odor of 5-androst-16-en-3-one (androstenone), a testosterone metabolite, shows wide variations among unrelated individuals. Analysis of correlations in sensitivity between monozygotic twin pairs, dizygotic twin pairs, and nontwin sib pairs now shows that at least a portion of this variation is genetically determined. However, although data from some mouse studies have suggested a relationship between olfaction and the murine histocompatibility system (H-2), we were unable to demonstrate any role of the human HLA system in explaining the wide individual variations in human sensitivity to androstenone. An additional analysis of HLA antigens among 61 human mating pairs also provided no evidence that HLA phenotypes play a role in human mating preference. These data fail to support a role for the human HLA system in the recognition of an odorant of potential biological significance.
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The genetic polymorphism of properdin factor B (BF) was studied in different populations. The rarer alleles, BF*F1 and BF*S1, occurred in Caucasians, were less frequent in North American blacks, and were not demonstrated in any of three Oriental populations studied. Two further alleles of BF, termed BF*FM and BF*SM, were found to exist in these populations. The BF*FM allele, which was found only in Caucasians, codes for a functionally inactive factor-B product, whereas the BF*SM allele (found in a single Chinese individual), like other alleles of BF, codes for a functionally active product. HLA haplotype analyses in individuals carrying the rarer alleles of BF revealed not only a strong association between BF*F1 and HLA-B18 and BF*S1 and HLA-Bw50 but an even stronger association between these BF alleles and alleles of the two C4 loci. BF*F1 occurred most frequently on a C4A*3,B*Q0 haplotype, whereas the BF*S1 allele was usually found on a C4A*2,B*1/B*Q0 haplotype. HLA haplotypes carrying the BF*FM and BF*SM alleles all carried the more common C*4A3,B*1 haplotype.
The HLA genotypes of members of 104 families of patients with acute myelogenous leukemia (AML), 89 families of patients with acute lymphocytic leukemia (ALL), and 40 control families were analyzed. The results indicate that the HLA genotype of both ALL and AML leukemic patients is found more frequently than the expected 25% among their siblings; the increase for AML patients is statistically significant. This suggests that an HLA-linked factor(s) conferring susceptibility to leukemia may also be associated with increased gametic survival. The chance of finding an HLA-matched sibling for bone marrow transplantation is increased.
Hormonal studies and human leukocyte antigen (HLA) genotyping were performed in 5 males and 13 females who were demonstrated to have 21-hydroxylase deficiency. The enzymatic deficiency of steroidogenesis was detected by family studies of 10 females who presented with varying symptoms of androgen excess. The 10 index cases had normal genitalia at birth, but virilized to varying degrees postnatally. The additional 8 affected family members had not sought medical care, but some were found to have signs of virilization on physical examination, while others were normal. Thus both late-onset (symptomatic) and cryptic asymptomatic) 21-hydroxylase deficiency occurred in the same pedigree. The hormonal and genetic linkage studies indicate that the late-onset (symptomatic) form of 21-hydroxylase deficiency, like the cryptic (asymptomatic) and classical forms of 21-hydroxylase deficiency, is transmitted by an autosomal recessive gene which is linked to HLA-B. Furthermore, the classical form of 21-hydroxylase deficiency associated with prenatal virilization is transmitted by an allelic variant for steroid 21-hydroxylase different from that of the nonclassical forms, late-onset (symptomatic) and cryptic (asymptomatic) 21-hydroxylase deficiency. Although these latter 2 disorders have different clinical manifestations, they demonstrate a similar degree of steroid 21-hydroxylase deficiency that is less severe than that observed in classical 21-hydroxylase deficiency. The hormonal and genetic linkage data indicate that cryptic (asymptomatic) and late-onset (symptomatic) 21-hydroxylase deficiency result from the same allelic variant at the steroid 21-hydroxylase locus. A glossary of terms is presented to describe the various allelic forms of 21-hydroxylase deficiency with consistency.
The expression of HLA-A, -B, -C, and -DR antigens has been analyzed in 145 unrelated Caucasian patients with germ cell tumors of the testis. Eighteen of these patients had pure seminoma, while the remaining patients had nonseminomatous tumors with embryonal carcinoma, teratocarcinoma, choriocarcinoma, and/or yolk sac components, with or without seminoma. Increases were noted in the frequencies of Aw33, B5, DR5, and DRw6 among the patients with pure seminoma, A3 and B7 among the patients with embryonal carcinoma with or without seminoma, and Aw32 among the patients with yolk sac tumor components. A decrease in the frequency of HLA-DR3 was noted in all patients subgroups, although none of these differences were statistically significant after correction for the number of antigens tested. HLA typing results for three affected brothers of patients indicate that, in each family, the affected sibling pair share at least one HLA haplotype. The etiological and prognostic significance of this finding and of the increases in a few HLA antigen frequencies in particular patient groups and the overall decreases in DR3 remain to be determined.
A new case of rhino-entomophtoromycosis due to Conidiobolus coronatus is added to the ten others observed in Cameroon, among the 62 african cases described. The patient, a man 27 years old, has an elephantiasis form with nasal obstruction, hypertrophy of lips, globulous forms of cheeks, giving a monstrous facies. After failure of KI and intravenous miconazole, therapeutic success was obtained with oral ketoconazole. After improvement with 400 mg daily, the doses were increased to 600 mg to obtain mycological and clinical cure with good clinical and biological tolerance; important eosinophilia related to the destruction of the fungus was observed. Restorative surgery was necessary to render a more human aspect of the monstrous lesions of face.
Three classes of important mycoses in O.R.L. field can be recognized according to the responsible fungi and to thier physiopathology: 1) mycoses due to cosmopolite, opportunistic fungi, yeast-like fungi (Candida albicans, Cryptococcus neoformans, Torulopsis glabrata) or filamentous fungi (Aspergillaceae, Mucoraceae, Penicillia, etc...) invading a compromised host by antibiotics, immunosuppressors, radiotherapy or by severe diseases (hemopathia, diabetes with acidosis). The oropharyngolaryngeal candidosis, the black tongue (a polyfungal syndrome), the sinusal aspergillosis, the otomycoses, the nasalorbital cerebral form of mucormycosis are reviewed and the allergic accompanying symptoms described. 2) deep, systemic mycoses of tropical origin with respiratory entry and oral pharyngeal laryngeal metastatic localizations (histoplasmosis, blastomycosis, paracoccidioidomycosis, coccidioimycosis); the histoplasmosis represent actually the principal imported systemic mycosis with O.R.L. localization. 3) tropical and african mycosis localized exclusively in O.R.L. area (rhino-enthomophtoromycosis and rhinosporidosis).
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R-type vitamin B12 binding proteins (R proteins) from human granulocytes, erythrocytes, plasma, and other body fluids were characterized by isoprotein banding patterns on autoradiograms after resolution via thin-layer polyacrylamide isoelectric focusing (IEF) gel electrophoresis. R proteins obtained from various tissue sources in a given individual show tissue-specific electrophoretic patterns. The desialated R proteins obtained following in vitro treatment with neuraminidase are, however, the same for any given individual and do not show tissue specificity. The differences seen in native R proteins (i.e., transcobalamin I, III, and others) obtained from different tissues are due to variations only in the sialic acid content. Granulocytes from patients with chronic myelogenous leukemia (CML) contain both TC I and TC III, and these R proteins can be released in vitro by lithium stimulation. Normal granulocytes contain only TC III. Differences in desialated R proteins from individual to individual are due to a genetic polymorphism controlled by a single genetic locus (designated TCR) with two alleles, 1 and 2, which are found to be codominantly expressed in heterozygous individuals. The allelic variants of the desialated R proteins found in different blood cells and body fluids are controlled by only one genetic locus.
A human T lymphocyte antigen 4A (40,000 daltons) is defined by a monoclonal, complement- (C) fixing, hybridoma-produced antibody (moAb 4A). This antigen, which is identical to the previously reported antigen 3A 1, is expressed at quantitatively different levels on functional subsets of peripheral T lymphocytes as determined by the cell sensitivity to antibody and C. Peripheral T lymphocytes can be divided into two populations: 4A high-density T cells (4A increases), which are killed in vitro by moAb 4A + C, and 4A low-density T cells (4A decreases), which are not affected in vitro by moAb 4A + C treatment. The helper/inducer T cell lineage, defined by moAb Leu 3a, and the cytotoxic/suppressor T cell lineage, defined by moAb Leu 2A, contain both 4A increases and 4A decreases T cell populations. Functional studies by moAb 4A + C treatment show that 1) the 4A increases T cell population contains T helper cells, which are necessary for in vitro antibody production against red cell-bound determinant; 2) the 4A decreases T cell population contains the precursor T cells, which proliferate in vitro in MLC, and the precursor T cells, which are necessary for the in vitro generation of the alloreactive cytotoxic T cells; and 3) the cytotoxic activity of alloreactive T cells generated in CML assay is abrogated by moAb 4A + C treatment; 4) the activation of T cells by PHA and Con A increases the quantitative expression of 4A antigen.
A human cell line with strong natural killer (NK) activity lacking alloreactive cytotoxicity was derived from a primary mixed lymphocyte culture (MLC). The line was developed from a single colony grown in soft agarose and subsequently expanded in liquid culture. Several subcultures with identical reactivity were established, one of which (3.3) was studied in detail. The morphologic and phenotypic characteristics of this line were distinct from those of alloreactive T lymphocytes. While reacting with a moAb to the sheep red blood cell receptor, it lacked the well-defined pan T cell markers Leu 1 and Leu 4, as well as the markers associated with functional T cell subsets Leu 2a and Leu 3a. Further morphologic, histochemical, and phenotypic characterization revealed this cell line to be strikingly similar to the larger granular lymphocyte (LGL) population, which contains the bulk of the natural killer cell activity normally found in peripheral blood. Cold target blocking studies confirmed the NK specificity of the observed cytotoxicity. Although unlabeled NK targets readily inhibited cytotoxic activity, B-LCL bearing the stimulating antigens of the original MLC failed to inhibit lysis of NK-sensitive targets. The growth of 3.3 was strictly dependent on IL 2 CM. Absorption studies with IL 2-dependent T cells and 3.3 revealed that both of these cell populations were equally effective in removing the growth-promoting factor(s) from IL 2 CM. These data suggest that at least some of MLC-generated NK activity is mediated by a population of cells similar to if not identical to LGL. These cells, in addition, appear to depend on the same growth-promoting factor(s) in IL 2 CM as do classical T lymphocytes.
Histoplamosis is the most frequently imported tropical mycosis observed in France. Of the cases reported in the published literature, 30 to 50 p. cent present buccopharyngeal lesions as the initial symptom revealing the presence of the disease, or forming part of a form involving multiple viscera (18.6). Since the first case reported in France in a thesis by Leger (13) in 1954, other french publications, mainly from dermatologists, stomatologists, or otorhinolaryngologists, have drawn attention to these misleading, little known buccal manifestations, that are often recognized only at a late stage (1, 4, 5, 8, 9, 10, 14, 15, 16). Five new cases treated at the Pasteur Institute Hospital are reported.
Lingual candidiasis is a condition arising from a multiple of causes, some of which are well known (thrush, etc...). Two cases of chronic lingual mycotic granuloma are presented, one of which was due to a candida, the diagnosis being confirmed by pathological examination and electrosyneresis. The course of this granuloma leads to the appearance of a true epidermoid carcinoma, as illustrated by the description of other cases that have been reported. Current therapy for the granuloma itself mainly depends on the employ of ketoconazole, but the unfavorable course of the affection raises the question of the need for associated surgery.
Numerous progresses are realized in the chemotherapy of mycoses, particularly in the field of deep mycoses due to 3 categories of systemic antifungal agents: polyenes (oral nystatin, oral and intravenous amphotericin B), 5-fluorocytosine (oral and intravenous) and imidazole derivatives (oral and intravenous miconazole, oral ketoconazole). The old drugs as nystatin and amphotericin B per os continue to have a remarkable effect in oro-pharyngeal candidosis, chiefly after sufficient local contact with the mucos membranes; topical preparation are effective in fungal O.R.L. localizations (aspergillar or candidal otomycoses, glossitis). IV amphotericin B is indicated in naso-orbital-cerebral mucor mycosis, nasosinusal aspergillosis, candidosis, entomophthoromycoses and particularly systemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis) in spite of severe toxicity. 5-fluorocytosine (100-200 mg/kg) has a limited spectrum to Candida, Cryptococcus neoformans, Aspergillus fumigatus infections if the strains are sensitive to this agent (5% primary resistance). Among the new imidazole derivatives, ketoconazole (400 mg/day) represent a revolutionary antifungal agent due to a very large antifungal spectrum, absence of toxicity, rapid diffusion by oral way, and high therapeutic efficiency in candidosis, histoplasmosis, blastomycosis, rhino-entomophthoromycosis... Oral miconazole has a poor diffusion into the tissues and by intravenous way necessitates several injections daily to obtain therapeutic levels. Numerous imidazole derivatives (econazole, miconazole, clotrimazole etc...) can be successfully utilized by topical application, as well as numerous other local antifungal agents.