Int J Dermatol, 1988 Nov, 27(9), 633 - 7 Polymorphonuclear leukocyte functions in psoriasis; Goihman-Yahr M et al.; Circulating polymorphonuclear leukocyte (CPMN) functions were studied in patients with widespread psoriasis as well as in persons with chronic alcoholic liver disease (CALD), paracoccidioidomycosis, diverse granulomatous diseases, and normal individuals . We were unable to find stimulation or increase in CPMN functions in patients with psoriasis compared to normal individuals . Leukocytes from individuals with CALD had a lowering of their metabolic activation, chemotaxis, random movement, and adherence . CPMNs from patients with paracoccidioidomycosis showed a significant deficiency in their ability to digest Paracoccidioides brasiliensis . Our results are against the concept that functions of circulating PMNs are stimulated in psoriatics. Mycopathologia, 1988 Nov, 104(2), 87 - 91 Measurement of glucose-6-phosphate dehydrogenase and glutathione reductase activity in patients with paracoccidioidomycosis treated with ketoconazole; Barraviera B et al.; Hemoglobin rates, hematocrit and glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase activities were measured in 38 patients with paracoccidioidomycosis treated with ketoconazole or sulfadoxin, and in 13 normal individuals . Ketoconazole-treated patients showed reduced G6PD and glutathione reductase activities . One of these patients was found to be G6PD-deficient and suffered a hemolytic episode during treatment, which, however, did not require interruption of therapy . The authors suggest that patients showing an erythrocyte enzyme defect should be monitored hematologically during treatment with ketoconazole . They also suggest that ketoconazole is an oxidant drug in addition to being a possible inhibitor of antioxidant erythrocyte enzymes. Infect Immun, 1988 Nov, 56(11), 2997 - 3000 Cell walls from avirulent variants of Histoplasma capsulatum lack alpha-(1,3)-glucan; Klimpel KR et al.; Cell wall composition of isogenic virulent-avirulent strain pairs of Histoplasma capsulatum varied markedly with respect to alpha-(1,3)-glucan content . When yeast cell walls were fractionated by standard techniques, the avirulent strains contained up to 1,000-fold less alpha-(1,3)-glucan than did their virulent parents . No alpha-(1,3)-glucan could be detected on the surface of the avirulent strain yeast cells if we used a mouse monoclonal antibody that recognized this polymer . A similar relationship between virulence and alpha-(1,3)-glucan has been described for Paracoccidioides brasiliensis . alpha-(1,3)-Glucan is also found in several other pathogenic fungi and may thus be an important common virulence determinant. Cell Immunol, 1988 Nov, 117(1), 1 - 11 Regulation of immune responses by T suppressor cells and by serum in chronic paracoccidioidomycosis; Castaneda E et al.; Regulation of cellular responses was studied during the course of chronic murine disseminated paracoccidioidomycosis . Regulation of peripheral blood lymphocyte (PBL) proliferative responses to concanavalin A (Con A) was studied in vitro by mixing PBL from infected and noninfected mice . PBL from mice infected for 18 weeks had depressed responses to Con A and they depressed the Con A responses of PBL from noninfected mice by 95% when they were mixed in a 1:1 ratio . After treatment of PBL from infected mice with anti-Lyt-2.2 antibody plus complement, the responses to Con A were increased to normal values . The percentage of T-cell subpopulations in PBL from infected mice did not differ significantly from those of normal mice . Immunoregulation of delayed-type hypersensitivity (DTH) responses to antigen by serum from infected animals was studied in mice 1 week after intranasal (i.n.) infection, a time when DTH responses were maximal . DTH responses to antigen 7 days after i.n . infection (10(7) CFU Paracoccidioides brasiliensis) were significantly reduced when 0.5 ml of immune mouse serum (ELISA antibody titer to P . brasiliensis antigens 1:10,240) was given i.v . 1 day before infection (P less than 0.01) or 1 day before skin testing (P less than 0.001) . Normal mouse serum did not have this effect . The results indicate that progression of chronic disseminated paracoccidioidomycosis was associated with the development of T-cell suppressor activity for Con A responses of PBL, and that DTH responses to antigen were depressed by the administration of serum with specific high titer antibodies. J Submicrosc Cytol Pathol, 1988 Oct, 20(4), 769 - 72 Lanthanum nitrate labelling of the outer cell wall surface of phagocytized Paracoccidioides loboi in human lobomycosis; Sesso A et al.; Lesioned skin tissues from a female Caiabi indian with lobomycosis were processed for routine electron microscopy using, in the initial steps, solutions containing 2% lanthanum nitrate . The pattern of tracer distribution suggests that the tracer penetrates into the cavity containing the parasite through exocytotic-like apertures situated at the cell wall outer region . The tracer also infiltrates the virtual space between the cell wall and its recovering membrane, spreading over varying areas of the outer surface of the cell wall . The contrast imparted to the pericellular macrophage space by the lanthanum nitrate enabled easy localization of fibrillar, cell wall derived material which reaches the adjacent extracellular milieu. J Clin Microbiol, 1988 Oct, 26(10), 2147 - 51 Production of Paracoccidioides brasiliensis exoantigens for immunodiffusion tests; De Camargo Z et al.; Growth curves of the yeast form of Paracoccidioides brasiliensis B-339 based on total and viable cell counts were determined . Crude culture filtrate antigens were obtained after 7, 10, 15, 20, 25, and 30 days of incubation . Different patterns of proteins were obtained by affinity chromatography on Sepharose 4B-immunoglobulin G complex made with immunoglobulin G from patients with paracoccidioidomycosis, with subsequent analyses by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and scanning densitometry . Three major proteins were excreted during the time course of a 30-day culture: a doublet at 20 to 21 kilodaltons (kDa) and molecules of 43 and 52 kDa . The 43-kDa antigen was present throughout the growth period, and its level reached a peak on days 15 to 20 and then decreased considerably toward day 30 . The antigenic preparations collected on days 7, 10, 15, and 20 gave better reactions in immunodiffusion tests than those collected on days 25 and 30 . The 7-day exoantigen gave a sensitivity of 97.1% and specificity of 100% on immunodiffusion . The main line of precipitation had a very high intensity, showing a total identity with that of a previously purified glycoprotein of 43 kDa . A 7-day crude exoantigen displayed a high level of sensitivity and specificity, being reproducible from batch to batch and retaining its activity for years when kept lyophilized . A protocol is recommended for the production of a stable diagnostic antigen to be used in immunodiffusion tests for paracoccidioidomycosis. J Submicrosc Cytol Pathol, 1988 Jul, 20(3), 537 - 48 Interaction between macrophage and parasite cells in lobomycosis . The thickened cell wall of Paracoccidioides loboi exhibits apertures to the extracellular milieu; Sesso A et al.; Lesioned, cutaneous, tissue fragments from five indians of the Caiabi tribe with lobomycosis, living in the Xingu National Park (Central Brazil), are analyzed by light and electron microscopy . Clusters of macrophages filled with parasite and/or cell wall debris, separated by collagen fiber bundles, characterize the morphological pattern seen in thick and thin sections . Paracoccidioides loboi within the phagocytic cells are multinucleate organisms whose cytoplasm contains mitochondria with few cristae, ribosomes and vacuoles; a large, dense, globular body and peculiarly curved mitochondrial profiles are described . From the outer portion of the double layered parasite cell wall, radial projections commonly emerge, rendering the structure conspicuously thicker and more irregularly surfaced than that seen in many other phagocytized yeast cell species . The cell wall layers from fungi possessing distinct subcellular organization show a weak or no reaction for acid phosphatase . Most of the foamy cells commonly seen by light microscopy are macrophages filled with fungal cell wall remnants which exhibit marked acid phosphatase activity . Occasionally, microchannels extending from the outer layer of the parasite cell wall to the macrophage surface and exocytic-like openings, possibly derived from the fusion of the macrophage membrane covering the parasite cell wall and the macrophage plasmalemma can be seen . Through such routes, material of texture and density similar to that of the outermost cell wall layer appears to be deposited extracellularly. Mycopathologia, 1988 Jul, 103(1), 35 - 42 Protective effect of prior immunization on ocular paracoccidioidomycosis in guinea pigs; Kamegasawa A et al.; The present study reproduced the experimental model of ocular paracoccidioidomycosis in guinea pigs, by the intracardiac inoculation of yeast-forms of P . brasiliensis . Ocular involvement was observed in 80% of the infected animals . The uvea, ciliary body, choroid, iris, lids and the conjunctiva were the structures most commonly affected . To protect the animals against the infection, an immunization protocol was standardized utilizing a P . brasiliensis soluble antigen in Freund's complete adjuvant, administered weekly, during 3 weeks, by the subcutaneous route . Two weeks later, previously immunized guinea pigs were challenged by the intracardiac route with yeast-forms of P . brasiliensis (vaccinated group) . When compared with a control group (infection in the absence of prior immunization), the vaccinated animals developed higher levels of anti-P . brasiliensis cellular and humoral immune response and a three times lower frequency of ocular involvement (85.7% vs 28.5%) . In addition, the ocular lesions were significantly more localized and contained less fungal cells . The data demonstrated that the subcutaneous immunization was effective in decreasing the frequency and extent of ocular lesions, as well as in blocking fungal multiplication. Mycopathologia, 1988 Jul, 103(1), 11 - 20 Connective matrix organization in chronic granulomas of experimental paracoccidioidomycosis; Kerr IB et al.; The histological and ultrastructural aspects of chronic granulomas from rats infected intraperitoneally with Paracoccidioides brasiliensis are described with special emphasis on the composition of the extracellular matrix . The granulomas were structurally arranged in two zones, one central containing fungi, and the other peripheral . The extracellular matrix was composed of collagen types I and III, proteoglycans, glycoprotein, and an undefined amorphous substance . The main cellular population was represented by macrophages, epithelioid cells, and giant cells in the central zone, and fibroblasts in the peripheral zone . The fibrotic process was a critical event in this stage of the infection, and showed a centrifugal direction . This might be provoked by direct stimulus from the fungi or by macrophage-fibroblastic interaction. Mycopathologia, 1988 Jul, 103(1), 3 - 9 Paracoccidioidomycosis in the region of Botucatu (state of São Paulo, Brazil) . Evaluation of serum thyroxine (T4) and triiodothyronine (T3) levels and of the response to thyrotropin releasing hormone (TRH); Kiy Y et al.; T4, T3 and TSH serum levels were measured in 25 patients with paracoccidioidomycosis . Thyroid T3 reserves were measured on the basis of the increase in T3 (delta T3) 2 h after intravenous injection of 200 micrograms TRH, and pituitary TSH reserves were measured on the basis of TSH increase (delta TSH) 20 min after the same injection . Twenty healthy volunteers with no history of thyroid disease were used as controls . When the two groups were compared, the following results were obtained: (a) there was no significant difference in mean T4, T3, delta TSH between groups; (b) reduced T3 levels were detected more frequently in patients with paracoccidioidomycosis, especially among those with the acute form of the disease or with the severely disseminated chronic form . The results suggest the occurrence of a reduction in peripheral conversion of T4 to T3, but do not indicate the occurrence of hypothyroidism in any of its forms (thyroid, pituitary or hypothalamic). Infect Immun, 1988 Jul, 56(7), 1771 - 7 Impairment of cellular but not humoral immune responses in chronic pulmonary and disseminated paracoccidioidomycosis in mice; Castaneda E et al.; Humoral and cellular immune responses were measured during the progression of chronic pulmonary and disseminated paracoccidioidomycosis in mice . The chronic disease was established by pulmonary infection of mice with different doses of the yeast form of Paracoccidioides brasiliensis isolate GAP . Levels of antibodies to P . brasiliensis, detected in serum by immunodiffusion and enzyme-linked immunosorbent assay, directly correlated with the size of the infectious challenge . Significant delayed-type hypersensitivity (DTH) responses to antigen were largely restricted to week 1 after pulmonary infection with intranasally administered high doses (5.0 x 10(6) or 1.1 x 10(7) CFU per inoculum) . In vitro lymphoproliferative responses of peripheral blood lymphocytes (PBL) to P . brasiliensis antigens were significant only at 2 weeks after infection with intranasally administered 1.1 x 10(7) CFU . Responses of PBL to concanavalin A were depressed (50% of control response) as early as 8 weeks and reached a nadir at 10 to 18 weeks after infection . Infected mice made antibodies to sheep erythrocytes (SRBC) (10(9) intravenously {i.v.}) normally at all times tested after infection . In contrast, infected mice sensitized to SRBC (10(6) i.v.) had significantly depressed DTH responses to SRBC at 9 and 20 weeks postinfection compared with noninfected mice . These results indicated that in this model, normal humoral responses developed to homologous and heterologous antigens . In contrast, the T cellular immune responses were depressed with progression and chronicity of the disease . Thus, this model closely mimics the immunological findings in human paracoccidioidomycosis. Allergol Immunopathol (Madr), 1988 Jul-Aug, 16(4), 215 - 8 Crossed-antigenicity between the etiologic agents of lobomycosis and paraccocidioidomycosis evidenced by an immunoenzymatic method (PAP); Landman G et al.; Lobomycosis or Keloidal blastomycosis and Paracoccidiodomycosis found in South American tropical regions are considered different mycoses from the clinical and mycological point of view . Very little is known about the immunology of Lobomycosis, since the etiological agent of this mycosis, Loboa loboi, is not cultured "in vitro" . In order to overcome this difficulty, a rabbit Paracoccidioides brasiliensis, antiserum is usually used, since crossed-antigenicity between both fungi has been demonstrated by serological methods and immunofluorescence . In this paper, common antigens between Loboa loboi and Paracoccidiodes brasiliensis were detected by means of rabbit serum against a metabolic antigen from Paracoccidiodies brasiliensis and using a peroxidase-antiperoxidase (PAP) technique . This method provided retrospective studies on three cases studied by using histological material from Lobomycosis stocked for a long time . The antigenic relationship between both fungi was confirmed by our results based on biopsies from Keloidal blastomycosis and Paracoccidioidomycosis, by using the PAP method and a rabbit serum against a metabolic antigen from Paracoccidioides brasiliensis. Mycopathologia, 1988 May, 102(2), 97 - 105 Lipid composition and effect of amphotericin B on yeast cells of Paracoccidioides brasiliensis; Hamdan JS et al.; Yeast cells of Paracoccidioides brasiliensis strain SN, were obtained for analysis of lipid composition . Total lipids, phospholipids, sterols, and qualitative sterols and fatty acid composition were determined . Such analysis were made on cells cultured in the presence or absence of amphotericin B and on non proliferating cell suspensions exposed to the antibiotic . Marked alterations in lipid contents were observed in this different conditions . The major alterations were the reduction of total lipids, sterols, and palmitoleic acid in both, proliferating and non proliferating antibiotic exposed cells . The effect of amphotericin B was evaluated also in terms of viability and release of intracellular substances, at different times of exposure . The minimal inhibitory concentration (MIC) determined for that strain of this fungus was 0.2 microgram/mL. Mycopathologia, 1988 May, 102(2), 87 - 96 Paracoccidioidomycosis: study of six cases with ocular involvement; Silva MR et al.; We present 6 patients with ocular involvement due to paracoccidioidomycosis . All cases were confirmed by the finding of Paracoccidioides brasiliensis in histopathological or direct mycologic examination of material from the lesion in the eyelid or conjunctiva . In two cases the bulbar conjunctiva was also involved, in another the cornea, and still another patient developed endophthalmitis . The presence of this mutilating disease which may lead to blindness should be suspected when chronic blepharitis or palpebral ulcerated papular lesions are detected in patients from endemic areas of paracoccidioidomycosis . This etiology should also be suspected in patients with anterior and posterior uveitis after discarding the most frequent causes of this condition. J Immunol, 1988 Apr 15, 140(8), 2786 - 9 In vivo and in vitro activation of pulmonary macrophages by IFN-gamma for enhanced killing of Paracoccidioides brasiliensis or Blastomyces dermatitidis; Brummer E et al.; The fungicidal capacity of murine pulmonary macrophages (PuM) activated in vitro with IFN or lymphokines or in vivo with IFN was studied . PuM treated overnight with IFN (1000 U/ml), Con A-stimulated spleen cell culture supernatants, or lymph node cells plus Con A significantly killed yeast cells of the Gar w isolate of Paracoccidioides brasiliensis 45.5 +/- 2.1%, 72.0 +/- 4.2%, and 51.5 +/- 0.7% respectively . Two other isolates of P . brasiliensis (Ru and LA) were also killed (45 and 34%) by PuM activated by lymph node cells plus Con A . Control PuM had lesser but significant capacity for killing of P . brasiliensis isolates, ranging from 15 to 22% . Killing of P . brasiliensis by PuM activated by Con A-stimulated spleen cell culture supernatants could not be significantly inhibited by superoxide dismutase, catalase, or azide . When mice were treated in vivo with 4 X 10(5) IFN U i.p . and PuM isolated 24 h later, the PuM had significantly enhanced ability to kill P . brasiliensis (47.0 +/- 6.3%) compared with PuM from control mice (25.0 +/- 4.2%) . PuM thus activated also showed enhanced killing (43%) of a second isolate compared with control PuM (22%) . PuM from IFN-treated mice were able to significantly kill Blastomyces dermatitidis (37.5 +/- 0.7%) compared with control PuM (4.5 +/- 6.3%) . These results show that PuM can be activated in vitro and in vivo by IFN for enhanced fungicidal activity against two pulmonary fungal pathogens and suggests that immunologic production of IFN could be an important factor in host defenses against these diseases. J Med Vet Mycol, 1988 Apr, 26(2), 113 - 8 Growth and production of iron chelants by Paracoccidioides brasiliensis mycelial and yeast forms; Arango R et al.; The mycelial and yeast forms of the fungus Paracoccidioides brasiliensis were cultured in a chemically defined liquid medium with different iron concentrations and the growth measured spectrophotometrically . The iron binding capacity of culture supernatants was measured by a colorimetric assay . Both the mycelial and yeast forms were able to grow in media containing trace amounts of iron (0.02 mgl-1) but when the iron chelant 1.10 phenantroline was added there was a delay in the initiation of growth of the yeast and almost total inhibition of the mycelium . When iron excess was added to media containing phenantroline, this inhibitory effect was reversed, partially for the mycelial, and completely for the yeast form . For both mycelial and yeast forms, the iron binding capacity of the culture supernatants was greater in media with low iron concentrations. J Med Vet Mycol, 1988 Apr, 26(2), 105 - 11 Mononuclear cell subsets in patients with different clinical forms of paracoccidioidomycosis; Mota NG et al.; Seventy untreated paracoccidioidomycosis patients, 15 with the acute or subacute form of the disease and 55 with the chronic form, were compared with two normal control groups of the same age range . Peripheral blood mononuclear cell subsets were defined by monoclonal antibodies directed at total T cells, helper/inducer and suppressor/cytotoxic T cell subpopulations; B cells, cortical thymocytes and monocyte/null cells . Both groups of patients showed an increased number of monocyte/null cells, a low helper/suppressor ratio and a reduced percentage of total T cells and their helper/inducer subsets . In addition patients with the acute form of the disease exhibited high levels of suppressor/cytotoxic T cells and B cells . These findings are of importance in our attempts to understand the pathogenesis of this mycosis and also to evaluate its prognosis in individual patients. Dis Colon Rectum, 1988 Mar, 31(3), 210 - 5 Spontaneous and evoked coccygeal pain in depression; Maroy B; Three hundred thirteen patients with signs of depression or spontaneous or evoked pain of coccygeal area were studied over six months . One hundred eighty (58 percent) had no spontaneous pain, 87 (28 percent) had moderate pain, and 46 (15 percent) a severe coccygodynia leading to consultation . In four of the latter group, no other sign of depression was found . Seventy-nine percent of the patients with spontaneous pain and 66 percent without spontaneous pain had coccygeal pain evoked by rectal digital examination (RDE) . Seventy-one percent of the patients with spontaneous pain and 56 percent without spontaneous pain had paracoccygeal pain evoked by RDE . Among severely depressed patients (Group III), 76 percent had an evoked pain and 80 percent a coccygeal pain--either spontaneous or evoked . In 178 (57 percent), all signs disappeared when treated with various antidepressants in seven visits and within six months . Seven (2 percent) were failures; 44 (14 percent) were lost during follow-up; 84 (27 percent) did not return after the first consultation . After treatment in five patients was stopped, all signs recurred together and disappeared when adapted treatment was administered again . In 120 consecutive patients who had colonic roentgenologic examination and no depressive sign, two had coccygeal and muscular pain at rectal touch . A highly significant correlation was found between the following parameters: evoked pain and depressive status in noncoccygodynic patients, coccygodynia and evoked pain, coccygeal and paracoccygeal muscular pain . Severity of coccygodynia was not correlated with the number of depressive signs . Sex, age, and treatment efficiency were not correlated . The mechanism of depressive pain is discussed . RDE-evoked pain is proposed as an "objective" diagnostic sign for masked depression and as a means of evolution control . The frequency of the disease and efficiency of treatment are stressed. Infect Immun, 1988 Mar, 56(3), 711 - 3 Inhibition by estrogens of conidium-to-yeast conversion in the fungus Paracoccidioides brasiliensis; Salazar ME et al.; Conidia produced by Paracoccidioides brasiliensis are inhibited by mammalian estrogens in their in vitro conversion into yeast-form cells . This was demonstrated with four different isolates . In these experiments, conversion was reduced to 10.7 and 34.4% of the control values by 17-beta-estradiol at 10(-6) and 10(-8) M, respectively . At the same concentrations, the synthetic estrogen diethylstilbestrol was slightly less inhibitory . In contrast, other sex hormones and analogs, i.e., testosterone, 17-alpha-estradiol, tamoxifen, and hydroxytamoxifen, had no effect on conidium-to-yeast conversion . Previous studies have shown that estrogens similarly inhibit mycelium-to-yeast-form transition in P . brasiliensis . Conidia, and not mycelial fragments, are believed to be the natural infectious propagules . These findings with conidia support the hypothesis that estrogens, affecting the initial host-parasite interactions by suppressing conversion to the parasitic form of the organism, are, at least in part, responsible for the greater resistance of females to paracoccidioidomycosis. Mycopathologia, 1988 Jan, 101(1), 3 - 11 Paracoccidioidomycosis in nude mice: presence of filamentous forms of the fungus; Kerr IB et al.; Congenitally athymic nude mice (nu/nu) and their phenotypically normal littermates (nu/+) were intraperitoneally infected with yeast cells of a strain of Paracoccidioides brasiliensis . The nude mice developed a severe and generalized infection with an intense parasitism of several organs, accompanied by a low-grade of tissue reaction . The lesions were characterized by abundant yeast-like cells of the fungus, and in some animals, numerous hyphal forms could be well visualized . In control animals, infection was moderate, almost exclusively restricted to the area of inoculation, and the lesions presented few parasites surrounded by an inflammatory response . Filamentous forms of the fungus were never encountered in these animals. J Med Vet Mycol, 1988, 26(6), 367 - 73 Secretion of the 43 kDa glycoprotein antigen by Paracoccidioides brasiliensis; Stambuk BU et al.; Yeast forms of the pathogenic fungus Paracoccidioides brasiliensis secrete into the culture supernatant a 43,000 daltons glycoprotein (Gp43) which can be immunoprecipitated specifically by sera from patients with paracoccidioidomycosis . We show here that following labelling of P . brasiliensis with (35S)methionine, Gp43 was detected as the major component in the culture supernatant fluid as early as 1 hour after addition of the radiolabel . The amount of Gp43, as determined by a competitive radioimmunoassay, or by staining total protein after sodium dodecylsulfate-polyacrylamide gel electrophoresis, progressively increased in the culture supernatant until the culture reached the late exponential phase . It then decreased and continued to do so in the stationary phase . These results indicate that Gp43 is continuously produced and secreted in the medium by actively growing yeasts and that cultures in the exponential phase of growth should be used for a maximal yield of this exocellular antigen. J Med Vet Mycol, 1988, 26(5), 269 - 76 Morphological study of a variant of Paracoccidioides brasiliensis that exists in the yeast form at room temperature; Villar LA et al.; Incubation of Paracoccidioides brasiliensis conidia at 20-25 degrees C (RT) results in two types of colonies, mycelial (M) and yeast (YRT) . A study of the latter colonies was undertaken . Conidia were plated in complex (BHI) and chemically-defined media (CDCM), with and without fetal calf serum (FCS) . Incubation was carried out at 21 degrees C for 4 weeks . The mean number of YRT colonies was approximately 18.5% on BHI agar . Selected YRT colonies were transferred to liquid CDCM, incubated 7 days at 21 degrees C and transferred to solid media; YRT appearance was preserved in 95% of the colonies if media were FCS-supplemented; otherwise, most colonies reverted to the M form . When FCS was replaced by bovine albumin or by alpha-globulin, 63% and 68% respectively of the colonies obtained after plating YRT cells, became mycelial . Comparative morphologic studies of both YRT and yeasts grown at 37 degrees C suggested that there were no major differences between these two types of yeast cells when size and budding were taken into consideration . The results indicate that in this particular variant, dimorphism is not exclusively temperature-dependent. J Med Vet Mycol, 1988, 26(4), 253 - 6 Increased frequency of HLA-B40 in patients with paracoccidioidomycosis; Lacerda GB et al.; The presence of 9 HLA-A and 14 HLA-B specificities was determined in 83 patients with paracoccidioidomycosis . The finding of a higher than normal incidence of HLA-B40 (chi 2 = 10.8; corrected P less than 0.026) supports the hypothesis that genetic factors may play a role in susceptibility to paracoccidioidomycosis . The risk of developing paracoccidioidomycosis is 4.3 times higher for individuals carrying HLA-B40 than for those lacking this antigen. Ann Pathol, 1988, 8(4-5), 328 - 31 {Buccal histoplasmosis . Apropos of a case with a difficult histopathologic diagnosis}; Loubiere R et al.; A 65-year-old man who had lived in several tropical countries, particularly in Brazil, is observed for an ulcerative lesion of the mouth that appeared two months ago . The biopsy reveals polymorphic granuloma with numerous giant cells . PAS and Gomori-Grocott stains show very numerous roundish structures of variable size (3 microns to 15 microns) . There are multiple buds like in paracoccidioidomycosis but culture reveals Histoplasma capsulatum . These abnormal forms have been described in large necrotic zones and especially in endocarditis (intravascular proliferations) . To our knowledge, it is the first description of these forms in primary infestation . This case shows the necessity to control histological diagnosis of mycosis . Culture and biological identification are absolutely necessary for specific diagnosis. Int J Immunopharmacol, 1988, 10(8), 945 - 52 Gamma-interferon activation of macrophages for killing of Paracoccidioides brasiliensis and evidence for nonoxidative mechanisms; Brummer E et al.; Fungicidal activity of murine peritoneal macrophages for the yeast form of the dimorphic fungal pathogen P . brasiliensis was studied . Killing was assessed by reduction of colony forming units (CFU) using a new medium which has a good plating efficiency . Resident peritoneal macrophages phagocytosed but did not kill P . brasiliensis . Macrophages treated overnight with recombinant gamma-interferon (IFN), lymph node cells plus concanavalin A (Con A) or Con A-stimulated spleen cell culture supernatants (Con A Sup) reproducibly killed three different isolates of P . brasiliensis (35 - 55%, P less than 0.05 - P less than 0.001) . This is the first demonstration of killing of this organism by macrophages . Activated macrophages did not show enhanced phagocytosis of P . brasiliensis . Activation of macrophages for killing by IFN was dose-dependent and, varying with the isolate, 100 - 10,000 U/ml was required for inducing significant fungicidal effects against P . brasiliensis . Activation of macrophages by IFN or Con A Sup was abrogated by anti-IFN antibody . These results suggest that immune modulation may be an approach to therapy of paracoccidioidomycosis . Killing was not significantly inhibited in the presence of superoxide dismutase (450 U/ml), catalase (20,000 U/ml), dimethylsulfoxide (300 mM) or azide (1 mM) . This indicated that killing mechanism(s) did not depend upon products of the oxidative burst . These results show that P . brasiliensis can be significantly killed by activated macrophages without products of the oxidative burst. J Med Vet Mycol, 1988, 26(6), 351 - 8 A culture medium for Paracoccidioides brasiliensis with high plating efficiency, and the effect of siderophores; Castaneda E et al.; The plating efficiency of Paracoccidioides brasiliensis on standard mycological media is poor, impairing its isolation and recovery from various sources, particularly infected tissues . We describe a medium that markedly improves P . brasiliensis plating efficiency . It consists of a synthetic medium (modified McVeigh-Morton) supplemented with 4% (v:v) horse serum and 5% (v:v) culture filtrate from stationary phase P . brasiliensis cultures . A commercially available medium (brain-heart infusion), ordinarily inferior to unsupplemented McVeigh-Morton medium, is at least as efficacious as supplemented McVeigh-Morton medium when supplemented in this manner . We show that plating efficiency varies among P . brasiliensis isolates and can even vary with the isolate's history of passage in culture . In contrast, all isolates studied could produce the growth enhancing factors present in culture filtrate . Some siderophores produced by other fungi can be substituted for the culture filtrate, whereas others can be substituted for both the filtrate and serum . The enhancing effect of filtrate and/or serum could be removed by chelating iron . P . brasiliensis-produced siderophores are likely to be the growth enhancing moiety in culture filtrates. Braz J Med Biol Res, 1988, 21(5), 945 - 7 Intrinsic vascularization of granuloma in experimental paracoccidioidomycosis; Lenzi HL et al.; Rats infected with Paracoccidioides brasiliensis exhibited vascularized granulomas during the granulomatous stage, with more intensity on the 49th day after infection . These data change the classical belief that the granuloma is always an avascular structure . The authors suggest that the granuloma is under the balanced influence of angiogenic or angiostatic factors, with the usual predominance of the latter, with the consequent advantage of limited antigen diffusion to the vascular system. Arq Neuropsiquiatr, 1987 Dec, 45(4), 419 - 23 A new treatment for large cerebral paracoccidioidomycosis; Guerreiro CA et al.; A patient with a large paracoccidioidal granuloma in the right fronto-parietal region was treated with sulfamethoxazole-trimethoprim alone, without the use of amphotericin B or any surgical measures . The authors stress the excellent therapeutic results through a twenty-six month follow-up, documented by repeated CT scans. J Med Vet Mycol, 1987 Dec, 25(6), 377 - 87 Chronic pulmonary and disseminated paracoccidioidomycosis in mice: quantitation of progression and chronicity; Castaneda E et al.; An animal model of chronic paracoccidioidomycosis was established in male adult BALB/cByJIMR mice by intranasal instillation of different doses of yeast form Paracoccidioides brasiliensis . The inoculum was standardized in terms of virulence, age of the culture, percentage of multicellular fungal units containing 1-3 cells, and viability . Progression and chronicity of the infection was measured by quantitative counts of colony forming units (CFU) of P . brasiliensis from infected lungs, spleens, and livers in a newly developed culture medium . The body weight of the mice and the organ weights were also used to monitor the disease process . Infection with several challenge sizes progressed in the lungs until a maximum of 10(7)-10(8) CFU per lung was reached; in general, the higher the inoculum, the sooner this maximum was reached . In mice infected with 2.5 X 10(6) CFU the maximum was reached at 8 weeks, whereas in mice infected with 3 X 10(4) CFU the maximum was reached 14 weeks after infection . Dissemination of the disease progressed until there were 10(6)-10(7) CFU per spleen or liver . The higher the infective dose, the shorter the time required to reach a maximum stable population of yeasts in spleen and liver (12 weeks with inoculum of 2.5 X 10(6) CFU, 18-26 weeks with inoculum of 7.0 X 10(3) CFU) . The body weight of mice tended to diminish with time after infection compared to uninfected controls . In contrast, the weight of lung and spleen increased with time after infection . This model of chronic paracoccidioidomycosis permits evaluation of progression of the disease process and of the multiplication of the yeast in organs. J Med Vet Mycol, 1987 Oct, 25(5), 291 - 300 Experimental pulmonary paracoccidioidomycosis in the Syrian hamster: morphology and correlation of lesions with the immune response; Tani EM et al.; A model for pulmonary paracoccidioidomycosis in the hamster is described . The disease was induced by intratracheal inoculation of 1.7 x 10(5) viable yeast forms of P . brasiliensis . Lung histopathology, dissemination lesions and humoral and cellular immune responses were investigated at intervals up to 24 weeks after infection . Humoral immunity was studied by immunodiffusion and complement fixation tests . Cell-mediated immunity was evaluated in vitro by the macrophage migration inhibition test in the presence of phytohaemagglutinin and P . brasiliensis soluble antigen, and in vivo by the paracoccidioidin test . Thirty out of 35 infected animals (85.7%) developed pulmonary paracoccidioidomycosis . Dissemination lesions were observed in regional lymph nodes (82.8%), liver (8.5%) and spleen (5.7%) . Lung involvement was mainly around bronchi and vessels . Regional lymph nodes were severely involved from the fourth week on, acquiring a pseudotumoral aspect at later stages . Specific antibodies were detected from the fourth week on, with titres increasing progressively . The cellular immune response to phytohaemagglutinin was intact throughout the experiment and the response to P . brasiliensis antigen was already detectable by the second week and remained positive to the end of the experiment . The skin test became positive from the fourth week on . Inoculation by the intratracheal route represents a highly effective way of infecting hamsters with P . brasiliensis, with the induction of localized disease, good antibody production and intact cell immunity. J Med Vet Mycol, 1987 Oct, 25(5), 343 - 5 Nuclear staining of Paracoccidioides brasiliensis conidia; McEwen JG et al.; More than 80% of the conidia produced by two different isolates of Paracoccidioides brasiliensis, were found to be uninucleate; however, when they were incubated at 37 degrees C and began to transform into yeast cells, they became bi- or multi-nucleated, so that when most of the conidia had already transformed into yeast cells (72-96 h), there were at least four or five nuclei per cell in approximately 80% of the conidia examined. J Bacteriol, 1987 Sep, 169(9), 4055 - 60 Mycelial- to yeast-phase transitions of the dimorphic fungi Blastomyces dermatitidis and Paracoccidioides brasiliensis; Medoff G et al.; The physiological changes that occur during the mycelial- to yeast-phase transitions induced by a temperature shift from 25 to 37 degrees C of cultures of Blastomyces dermatitidis and Paracoccidioides brasiliensis can be divided into three stages . The triggering event is a heat-related insult induced by the temperature shift which results in partial uncoupling of oxidative phosphorylation and declines in cellular ATP levels, respiration rates, and concentrations of electron transport components (stage 1) . The cells then enter a stage in which spontaneous respiration ceases (stage 2), and finally, there is a shift into a recovery phase during which transformation to yeast morphology occurs (stage 3) . Cysteine is required during stage 2 for the operation of shunt pathways which permit electron transport to bypass blocked portions of the cytochrome system . The mycelial- to yeast-phase transitions of these two fungi are very similar to that of Histoplasma capsulatum . Therefore, these three dimorphic fungal pathogens have evolved parallel mechanisms to adjust to the temperature shifts which induce these mycelial- to yeast-phase transitions. Mycopathologia, 1987 Aug, 99(2), 119 - 28 Growth curves, morphology and ultrastructure of ten Paracoccidioides brasiliensis isolates; Kashino SS et al.; The yeast phase of ten P . brasiliensis isolates were studied to characterize their growth pattern, morphology and ultrastructure . Growth curves were determined after counts of total and viable fungi units (FU) during 20 days . Three growth patterns were observed: slow, reaching approximately 10-30 X 10(6) FU/tube (Pb 18, Pb 265 and PB 2); intermediate, reaching 60-150 X 10(6) FU/tube (IVIC Pb 9, IVIC Pb 267, Pb SN, Pb Vitor and Pb Campo Grande) and fast, reaching 180-370 X 10(6) FU/tube (Pb 2052 and Pb 192) . The highest percentage of viable cells occurred on the 6th day of culture for Pb 192, Pb Campo Grande, Pb 2052 and IVIC Pb 9; on the 8th day for Pb Vitor, Pb SN, Pb 18 and IVIC Pb 267; on the 10th day for Pb 265 and on the 12th day of culture for Pb 2 . Mean generation times varied from approximately 21.2 (Pb 2052) to 102.6 hours (Pb 265) . The isolates showed similar morphology, except IVIC Pb 267 which did not present a typical yeast-phase at 35 degrees C and the two fast-growing isolates (Pb 2052 and Pb 192) that presented smaller cell sizes and less tendency to clump . The ultrastructure of the isolates was similar: the cell walls presented a width of 0.1 to 0.2 mu; the mitochondria presented few cristae and had equivalent patterns of distribution and morphology; the endoplasmic reticulum was scanty, presenting narrow cisternae; the vacuoles, empty or filled with electron-dense material, were numerous and two to five nuclei with pores were constantly observed. Infect Immun, 1987 Aug, 55(8), 1919 - 23 Resistance to Paracoccidioides brasiliensis in mice is controlled by a single dominant autosomal gene; Calich VL et al.; In a previous report it was shown that there are resistant, susceptible, and intermediate strains of mice to intraperitoneal Paracoccidioides brasiliensis infection . In the present work, we investigated the type of inheritance and the number of genes that determine resistance to paracoccidioidomycosis . Parental and hybrid mice were inoculated intraperitoneally with 5 X 10(6) P . brasiliensis yeast cells, and mortality was scored daily . Analysis of susceptible and resistant parental strains and of F1, F2, and backcross mice showed that the resistance to P . brasiliensis seems to be controlled genetically by a single dominant gene, which we designated the Pbr locus . The mean survival times of susceptible F2 and backcross hybrids were very similar to that of the susceptible parent . Examination of the pathological changes observed in parental and F1 mice, 6 months after infection, showed that F1 offspring presented a similar number and distribution of lesions to those of the resistant strains . The Pbr gene is not linked to H-2, Hc, and albino genes . Furthermore, resistance to paracoccidioidomycosis is controlled by an autosomal gene. J Med Vet Mycol, 1987 Jun, 25(3), 165 - 75 Experimental murine paracoccidiodomycosis induced by the inhalation of conidia; McEwen JG et al.; Adult BALB/c mice of both sexes were infected intranasally with 10(6) viable P . brasiliensis conidia . Animals were sacrificed at intervals up to 6 months and studied by histopathology and organ cultures . At the time of challenge lung sections showed that instilled conidia had reached the alveoli; at 12 h such conidia were transforming into yeast cells, with multiple buds appearing by 18 h . Initially, the cellular infiltrate was composed of polymorphonuclear leukocytes; 6 days later, lymphocytes, plasmocytes and macrophages predominated . Multinucleated giant cells appeared only after 6 weeks . The rate of pulmonary infection as determined by organ culture was high (82 of the 83 mice studied) . The experimental infection was progressive as indicated by increasing numbers of viable fungi with time . The results of this study demonstrate that the conidia produced by P . brasiliensis mycelial form are infectious, producing active disease in healthy animals. Am J Trop Med Hyg, 1987 May, 36(3), 603 - 8 Effect of murine polymorphonuclear leukocytes on the yeast form of Paracoccidioides brasiliensis {corrected}; McEwen JG et al.; The fungicidal activity of murine polymorphonuclear neutrophils from the peripheral blood or elicited intraperitoneally with thioglycollate or with antigen in Paracoccidioides brasiliensis-sensitized {corrected} or nonsensitized mice was studied . Although peripheral blood, thioglycollate-elicited, and antigen-elicited neutrophils from normal mice or thioglycollate-elicited neutrophils from P . brasiliensis-sensitized {corrected} mice killed Candida albicans (57% to 84%), they failed to significantly reduce inoculum colony forming units of P . brasiliensis {corrected} (0% to 13%) . In contrast, antigen-elicited neutrophils from sensitized mice reduced colony forming units of P . brasiliensis {corrected} by 40%, and exhibited significantly enhanced candidacidal activity compared to thioglycollate-elicited neutrophils from normal or sensitized mice but not peripheral blood neutrophils from normal mice . Fresh serum, but not specific antibody, was required for optimal killing of P . brasiliensis {corrected}, presumably representing an essential role for complement . Killing of P . brasiliensis {corrected} by antigen-elicited neutrophils from sensitized mice correlated with their ability to produce an enhanced oxidative burst, as measured by luminol-assisted chemiluminescence, when interacting with killed P . brasiliensis {corrected} cells . These results indicate that in P . brasiliensis-sensitized {corrected} hosts an inflammatory reaction to P . brasiliensis {corrected} results in activation of neutrophils for significant killing of the pathogen. Arch Dermatol, 1987 Apr, 123(4), 479 - 81 Langerhans' cells in paracoccidioidomycosis; Gimenez MF et al.; Langerhans' cells (LCs) appear to be altered in diseases that express a depressed cellular immune response . We measured the density of LCs in the skin of patients with the disseminated form of paracoccidioidomycosis . The study was performed using adenosine triphosphatase staining of epidermal sheets . Sixteen patients with paracoccidioidomycosis were evaluated . They had a highly significant reduction in LCs (LCs, 323 +/- 135/mm2) when compared with the number (LCs, 689 +/- 204/mm2) found in the control subjects . Morphological alterations of these cells were noted in patients with low numbers of LCs . These findings may reflect the depressed cellular immunity secondary to the infection with Paracoccidioides brasiliensis. Mycopathologia, 1987 Apr, 98(1), 27 - 34 Ketoconazole in the treatment of experimental murine paracoccidioidomycosis; Ueda AK et al.; In a murine model of chronic disseminated paracoccidioidomycosis (strain 18; intravenous route), Ketoconazole (200 mg/kg in 0.2% agar) was given daily by gavage in three different schedules . Continuous treatment from an early stage of infection (day 3) up to week 20 was the most effective protocol, leading to remission of histopathological lesions and of both humoral and cellular anti-P . brasiliensis immune response, and clearance of the fungus in lungs; only 1 treated animal at week 20 showed pulmonary granulomas, although less extensive than control mice . Continuous treatment from early stage up to week 8, followed by a 16 week-period of drug discontinuity, caused remission of lesions in all but 3 treated mice which showed active pulmonary paracoccidioidomycosis similar to controls (14.2% of unresponsiveness to treatment) . The continuous Ketoconazole protocol since a late stage of infection (week 4) up to week 20 produced a slower remission of lesions and immune response when compared with the first drug schedule . In this model of paracoccidioidomycosis, Ketoconazole showed no detectable side-effects and was a very effective drug especially in a prolonged administration protocol from an early stage of infection. Mycopathologia, 1987 Mar, 97(3), 189 - 93 A case of pseudoparacoccidioidomycosis: detection of the yeast phase of Mucor circinelloides in a clinical specimen; Cooper BH; A case is presented in which yeastlike cells resembling the yeast phase of Paracoccidioides brasiliensis were observed by microscopic examination of a urine sample . A mold identified as Mucor circinelloides was isolated from the specimen . It was converted to the yeast form by cultivation on Sabouraud agar incubated in a GasPak jar at 37 degrees C . The isolate was eventually shown not to be related to the patient's illness; however, the superficial resemblance of the yeast phase to P . brasiliensis caused some confusion in making a correct diagnosis. J Med Vet Mycol, 1987 Feb, 25(1), 5 - 18 Host-parasite relationships in paracoccidioidomycosis; Franco M; A viewpoint of host-parasite relationships in paracoccidioidomycosis is presented . The characteristics of the fungus which are important to the host-parasite interaction are discussed . Aspects of inhibition of mycelium-to-yeast transformation by estrogens acting at receptors on the fungal wall and in the cytoplasm, and the role of polysaccharide components of the cell wall in virulence are reviewed . The natural mechanisms of host defense are also examined, including phagocytosis, complement system, natural-killer cells and genetic control of resistance and susceptibility . Finally, a discussion of granuloma morphogenesis and its relationship to the humoral and cellular anti-P . brasiliensis immune response is presented. Trop Geogr Med, 1987 Jan, 39(1), 83 - 5 Paracoccidioidomycosis in Trinidad; Jankey N et al.; Paracoccidioidomycosis is a systemic disease endemic to South America, but rarely recognised in other parts of the world . The patient we describe represents the first case of paracoccidioidomycosis observed in Trinidad. Mycopathologia, 1987 Jan, 97(1), 3 - 7 The role of fractions from Paracoccidioides brasiliensis in the genesis of inflammatory response; Alves LM et al.; The influx of inflammatory cells towards the peritoneal cavity in rats inoculated intraperitoneally with subcellular preparations of the fungus Paracoccidioides brasiliensis was studied . In addition to the dead fungus, also fractions F1 of the cell wall, which mainly consisted of polysaccharides and the lipid extract, induced intense cell migration 4 hr after inoculation, with a greatly increased number of polymorphonuclear leucocytes (PMN) . Study of the kinetics of cell influx showed that both fraction F1 and the lipid extract initially induced intense PMN migration between the 4th and 24th hr after inoculation of these agents, followed by migration of mononuclear cells (MN) around the 48th hr . We also observed that migration of these cells increased gradually after inoculation of growing doses of fraction F1 . The present data suggest that polysaccharides and lipids isolated from P . brasiliensis may participate in the initial phase of the inflammatory response in paracoccidioidomycosis. Braz J Med Biol Res, 1987, 20(5), 587 - 9 Experimental paracoccidioidomycosis: early immunosuppression occurs in susceptible mice after infection with pathogenic fungi; Teixeira HC et al.; The course of Paracoccidioides brasiliensis infection depends on the natural resistance of the host and on the virulence of the fungus isolate . In the present study the immune response to sheep red blood cells (SRBC) was investigated in susceptible (B10.A) and resistant (A/SN) mice after intraperitoneal (ip) infection with pathogenic (Pb18) and apathogenic (IVIC Pb267) P . brasiliensis isolates . Infection with Pb18 yeast cells quickly induces a state of immunodepression only in the susceptible mice . This immunosuppression was not observed when mice were inoculated with IVIC Pb267 yeast. Trans R Soc Trop Med Hyg, 1987, 81(1), 46 - 8 Paracoccidioidin sensitization in Guyana--a preliminary skin test survey in hospitalized patients and laboratory workers; Hay RJ et al.; Thirty-one percent of a group of 49 hospitalized patients or laboratory workers in Guyana showed positive intradermal paracoccidioidin tests in the presence of negative histoplasmin reactions . In 2 patients (4%), the intradermal reactions to paracoccidioidin were greater than 10 mm in diameter . The prevalence of positive reactors in a selected population suggests that paracoccidioidomycosis may be endemic in Guyana although no clinical case has been reported from the country . A further survey in a larger, unselected population would lead to a clearer understanding of the problem. Mycopathologia, 1987 Jan, 97(1), 61 - 4 Prevalence of paracoccidioidomycosis in hospitalized adults in Rio de Janeiro (RJ) Brazil; Ferreire-da-Cruz MF et al.; Double immunodiffusion were used as screening test for the diagnosis of paracoccidioidomycosis . Five hundred hospitalized adults from general (150 patients--group I) and from a specialized chest disease hospital (350 patients--group II), were tested . All of them were without definitive etiological diagnosis and clinical specimens were obtained from the patients with positive serology . Testing sera obtained from 150 patients of the group I, fifty six cases of paracoccidioidomycosis were diagnosed . Specimens for mycological examination were subsequently obtained from 50 of these patients; P . brasiliensis could be recovered in 49 (98%) . Fundamental importance was the finding of 17 (4.8%) cases of paracoccidioidomycosis among the 350 patients referred from a chest disease hospital (group II) . Serological evidence of paracoccidioidomycosis found in 73 (14.6%) of the 500 screened patients, indicates a relatively high prevalence of this mycosis in adults patients admitted to several hospitals in RJ . These data probably do not reflect the real prevalence of paracoccidioidomycosis in RJ and should be considered as a gross underestimation . Thus, attention should also be paid to juvenile forms and DID could be of a great value in screening these cases too. Rev Infect Dis, 1987 Jan-Feb, 9 Suppl 1, S57 - 63 A clinical trial of itraconazole in the treatment of deep mycoses and leishmaniasis; Borelli D; Itraconazole was administered orally to two patients with sporotrichosis, 10 patients with paracoccidioidomycosis, three with mycetomas (due to Madurella grisea, Streptomyces madurae, and Pseudochaetosphaeronema larense, respectively), nine with chromomycosis due to Cladosporium carrionii, five with chromomycosis due to Fonsecaea pedrosoi and five with leishmaniasis (including one with the nodular disseminated form) . The clinical and laboratory tests showed excellent tolerance to the drug with a total absence of adverse reactions . Satisfactory results were achieved against paracoccidioidomycosis, sporotrichosis, and chromomycosis due to C . carrionii (apparent cure was achieved in a short time) . Encouraging improvement was noted in the treatment of mycetoma due to M . grisea . Among the five cases of leishmaniasis, a complete clearing was achieved in one and an encouraging improvement in two, including the one with the nodular disseminated form . Two patients with F . pedrosoi infection were apparently cured after the addition of thermotherapy and flucytosine, respectively, to the treatment regimen. Rev Infect Dis, 1987 Jan-Feb, 9 Suppl 1, S51 - 6 Itraconazole in the treatment of paracoccidioidomycosis: a preliminary report; Restrepo A et al.; The preliminary results of itraconazole therapy in 16 patients with active paracoccidioidomycosis were evaluated . The course of therapy--itraconazole administration for six months at a dose of 100 mg per day--was completed in 13 cases . This new triazole appeared as effective as ketoconazole in reducing the symptoms and arresting the progression of the mycosis . The scoring system employed to evaluate the effect of the drug showed that the condition of no patient worsened or remained the same during therapy . On the contrary, 11 (84.6%) of the 13 patients experienced major improvement and the other two (15.4%), minor improvement . No adverse reactions were reported by the patients, and there were no toxic effects on bone marrow or liver . Although experience with itraconazole is still limited, results to date indicate that this new drug is safe and effective for the treatment of paracoccidioidomycosis . Further trials with shorter periods of therapy seem warranted. Rev Infect Dis, 1987 Jan-Feb, 9 Suppl 1, S47 - 50 Oral treatment of paracoccidioidomycosis and histoplasmosis with itraconazole in humans; Negroni R et al.; Twenty-five patients with paracoccidioidomycosis and 17 patients with histoplasmosis were treated with itraconazole . All patients were adults . Those with paracoccidioidomycosis exhibited the chronic disseminated form of the disease; 21 of these patients had lesions in two or more locations, and four had lesions only on the larynx or mouth . Itraconazole was administered at a daily dosage of 50 mg for six months in the majority of these cases . All infections were clinically cured or showed striking improvement . Patients with histoplasmosis had the chronic pulmonary or chronic disseminated form of the disease . A daily dose of 100 mg was administered until clinical cure was established; the dose was then changed to 50 mg until the completion of six months of treatment . Twelve infections were clinically cured; four were strikingly alleviated . The remaining patient, who discontinued treatment with itraconazole after two months, had a severe relapse and died of respiratory failure. Med Cutan Ibero Lat Am, 1987, 15(6), 455 - 60 {Comparative study of the efficiency of itraconazole and ketoconazole in the treatment of experimental paracoccidioidomycosis}; Negroni R et al.; A comparative study between ketoconazole and itraconazole in the prophylactic and curative treatment of experimental paracoccidioidomycosis in rats and guinea pigs was carried out . Ninety seven Wistar rats were inoculated intracardiacally with the yeast-phase of P . brasiliensis with the purpose of evaluating the prophylactic treatment . Eighty one guinea pigs were injected intratesticularly with the same microorganism with the aim of studying the healing treatment . Both drugs were administered by gavage once a day . The prophylactic treatment started 3 days before the challenger inoculation and the healing treatment begun 10 days after the challenger inoculation . The animals were divided in four groups: I), control animals to which only the solvents of both drugs were administered; II), those which received ketoconazole 40 mg/kg/day; III), those treated with the same drug 80 mg/kg/day, and IV), animals treated with itraconazole 8 mg/kg/day . Seven to 30 days after starting the healing and prophylactic treatments the results were evaluated . Itraconazole seems to be as effective as ketoconazole at 5 fold lower dosage. J Med Vet Mycol, 1986 Dec, 24(6), 467 - 75 An evaluation of the enzyme-linked immunoabsorbent assay (ELISA) for quantitation of antibodies to Paracoccidioides brasiliensis; Cano LE et al.; The ELISA procedure was adapted for quantitation of antibodies against Paracoccidioides brasiliensis . Using a yeast cytoplasmic antigen and sera from patients with proven paracoccidioidomycosis, we found that 66% of sera reacted at titers greater than or equal to 1:128 . Titers of this magnitude were obtained only for 4-5% of sera from healthy blood donors, tuberculosis patients and patients with other systemic mycoses . The exception was sera from patients with histoplasmosis (36% had titers greater than or equal to 1:128) . Follow-up of 10 paracoccidioidomycosis patients during the course of therapy indicated a gradual decrease in antibody titers . Because of the technical advantages of the ELISA procedure in comparison with the standard complement fixation test, the ELISA test has potential utility for the quantitative determination of antibodies in patients with paracoccidioidomycosis. J Med Vet Mycol, 1986 Dec, 24(6), 445 - 54 A comparative histopathological, immunological, and biochemical study of experimental intravenous paracoccidioidomycosis induced in mice by three Paracoccidioides brasiliensis isolates; Zacharias D et al.; We carried out a comparative study of the histopathology (lung, liver, spleen, kidney and adrenals) and the anti-P . brasiliensis humoral (immunodiffusion test) and cellular (footpad test) immune response of mice intravenously inoculated with yeast forms of three P . brasiliensis isolates (Pb 18, Pb 192, Pb 265) . Pb 265 (avirulent strain) did not evoke specific lesions or antibody production; the levels of cellular immunity were significantly lower than those of the two other isolates . Lung granulomas induced by strain Pb 18 were richer in fungi and neutrophils and poorer in mononuclear cells when compared to those induced by strain Pb 192 . Extrapulmonary lesions were more frequent in mice infected with strain Pb 18 . Strains Pb 18 and Pb 192 raised similar humoral and cellular anti-P . brasiliensis responses . Cell wall analysis did not suggest striking differences among the strains . Slightly higher levels of the water soluble fraction 3 (which contains the immunogenic galactomannan and protein) were detected in strain Pb 265. Mycopathologia, 1986 Nov, 96(2), 123 - 30 Water as a substrate for the development of Paracoccidiodes brasiliensis mycelial form; de Bedout C et al.; Two isolates of P . brasiliensis in the mycelial form were studied for their capacity to survive and grow in sterile distilled water (SDW) . Inoculum for the experiments consisted of a spectrophotometrically-standardized suspension of washed and homogenized mycelial fragments; these had been obtained from 2-week old cultures grown in a synthetic medium (SM) . Series of tubes with SDW and SM were incubated with the above suspension and kept stationary for 6 months at either 4 degrees C or room temperature (RT) . Growth was measured by dry weight (DW) and turbidity (OD) determinations; additionally, CFU and ultrastructural appearance by transmission electron microscope (TEM) were assessed for one of the isolates . In general, cultures in SM at RT, grew exponentially after 2 weeks, becoming stationary for 7 weeks and then, declining abruptly . In SDW, fungal development was slow for 5 months when an increase in mass was recorded . When incubated at 4 degrees C, both SDW and SM cultures required longer time to develop but mass also increased . Morphologically, mycelial elements in SDW at RT exhibited increased lipid vacuoles and glycogen deposits but were otherwise normal up to 6 weeks when they presented the inter-hyphae-hyphae phenomenum . In SDW P . brasiliensis appears to utilize debris from its degenerated fungal partners to continue growing. J Med Vet Mycol, 1986 Aug, 24(4), 337 - 9 Morphological development of the conidia produced by Paracoccidioides brasiliensis mycelial form; Restrepo BI et al.; P . brasiliensis conidia were studied for their ability to grow as yeasts or as molds according to temperature . Using a microculture system we found that such conidia shared the ability of the parent mycelium to transform directly into multiple-budding yeast cells at 36 degrees C or to produce germ tubes and branching mycelia if kept at 22 degrees C. J Clin Invest, 1986 Aug, 78(2), 511 - 24 In vitro susceptibility of fungi to killing by neutrophil granulocytes discriminates between primary pathogenicity and opportunism; Schaffner A et al.; Pathogenic fungi, according to their propensity to cause infection of apparently normal individuals, can be grouped into either primary pathogens (e.g., Coccidioides, Histoplasma, Paracoccidioides, Blastomyces, and Sporothrix) or opportunists (e.g., Candida, Mucoraceae, Aspergillus spp., Petriellidium, and Trichosporon) . There is, however, no unifying concept explaining the difference between the virulence of the two fungal categories . Previously we have speculated that neutrophils are the common denominator of the high natural resistance to opportunistic fungi . Accordingly, we then compared the susceptibility to killing by neutrophil granulocytes of Histoplasma, Blastomyces, Paracoccidioides, and Sporothrix with that of 14 opportunistic fungi . We found the four virulent dimorphic yeasts, in contrast to opportunistic fungi, to be resistant to killing by neutrophils . Virulent dimorphic yeasts were ingested by neutrophils, and triggered a respiratory burst comparably to opportunists but were less susceptible to hydrogen peroxide, suggesting that differences in the susceptibility to microbicidal products of leukocytes may explain the difference in virulence. Infect Immun, 1986 Jul, 53(1), 199 - 206 Exocellular components of Paracoccidioides brasiliensis: identification of a specific antigen; Puccia R et al.; Yeast forms of Paracoccidioides brasiliensis grown in liquid medium produced exocellular components . Immunodiffusion reactions and immunoprecipitations of 131I-radiolabeled antigenic components with sera from patients having paracoccidioidomycosis (PCM) were used to monitor the isolation of specific constituents . Components having the main antigenic activity (fCon A) were isolated by exclusion from a Bio-Gel P30 column, followed by successive binding of eluted material to a Sepharose-concanavalin A column, and elution . The product contained, from sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, a minor 43,000-molecular-weight (MW) component (gp43), a polydisperse high-MW glycoconjugate, and a diffusely migrating 55,000-MW glycoprotein (gp55) . Other components, including a 72,000-MW glycoprotein, were irregularly expressed . The high-MW glycoconjugate complex contained, on the basis of methylation and 13C nuclear magnetic resonance data, a branched structure of mainly mannopyranosyl units . These were nonreducing ends, 6-O-, 2-O-, and 2,6-di-O-substituted, and the specific rotation of +16 degrees indicated that the glycosidic configurations of the units were alpha and beta in a ratio of ca . 1:1 (concanavalin A binding indicated that nonreducing ends or 2-O-substituted units or both of alpha-D-mannopyranose were present) . A small proportion of nonreducing end units of D-galactopyranose were also present in this polysaccharide . gp55 is a glycoprotein containing a complex carbohydrate moiety with fucose, mannose, galactose, and glucose, either as terminal nonreducing units or substituted in positions indicated by methylation data . Both PCM and normal human sera precipitated the high-MW glycoconjugate from 131I-labeled fCon A preparations, whereas gp55 was unreactive with human sera . gp43 was a specific antigenic component of P . brasiliensis culture filtrates which could be isolated in a pure form by gel filtration column chromatography (Sephadex G150) or by Sepharose-patient immunoglobulin G affinity chromatography . 131I-labeled gp43 reacted equally well with 10 PCM sera and hyperimmune rabbit serum against the band E antigen of Yarzabal at a 10(-3) dilution . At the same dilution, no reaction was detected with sera from normal individuals and from patients with other mycoses . Similarly, only PCM sera and the hyperimmune anti-E serum gave precipitin lines with gp43 in the less sensitive immunodiffusion tests . gp43 consisted of three components, with pI 6.7, 6.4 and 6.2, all of which reacted with PCM serum. Mycopathologia, 1986 Jun, 94(3), 133 - 44 Pathogenesis of paracoccidioidomycosis: a histopathological study of the experimental murine infection; Bedoya V et al.; The pathogenesis of primary pulmonary P . brasiliensis infection, the systemic dissemination which followed, and the histopathology of the main organs involved was studied in a murine model of chronic paracoccidioidomycosis . Adult male BALB/C mice, were challenged intranasally with 26 X 10(-6) viable P . brasiliensis yeast cells . We inoculated 86 animals which were sacrificed from 0 h to 20 weeks . As controls, 11 mice were instilled with saline solution, and 48 with 26 X 10(-6) heat-killed . P . brasiliensis yeast cells . None of the animals receiving saline, exhibited pathologic alterations; 11.6% of those inoculated with the heat-killed cells, revealed mild, transitory acino-pulmonary neutrophilic infiltrates . The animals infected with viable cells, developed a systemic process affecting mainly the lungs (46.5%), liver (18.6%), lymph-nodes (18.6%), and spleen (3.5%) . In this group of animals, lung lesions were detected regularly at all time periods from 3 h to 20 weeks . A multiple bronchopneumonic process was initially observed at 6 h, reached its maximum intensity around the third day, subsided thereafter but did not disappear and reactivated after the fifth week to become stationary until the end of experiments . Dissemination to other organs occurred early, and apparently by the hematogenous route . Initially the inflammatory cell infiltrate was mainly neutrophilic . With time, these cells were gradually replaced by lymphocytes, histiocytes and plasmocytes . Granuloma configuration of the cell infiltrate was distinctly seen around the fifth week, with multinucleated giant cells appearing at the ninth week . Hiliary lymph-node involvement was rare (7%) and primary lung lesions, as seen in tuberculosis and histoplasmosis, were not observed. J Med Vet Mycol, 1986 Jun, 24(3), 247 - 50 A technique to collect and dislodge conidia produced by Paracoccidioides brasiliensis mycelial form; Restrepo A et al.; Collection and separation of mycelial propagules produced by P . brasiliensis was accomplished by agitation with glass beads, centrifugation and filtration through cotton wool . The mean number of conidia liberated per plate (approximately 1 000 000) and their viability (79%), lead us to think that it is now possible to undertake experimental studies with these propagules. J Med Vet Mycol, 1986 Jun, 24(3), 235 - 7 Paracoccidioidomycosis case report: cure with amphotericin B and triple sulfa; Washburn RG et al.; A man developed paracoccidioidomycosis with non-productive cough and changes on chest roentgenogram one year following agricultural work in Ecuador . Oropharyngeal and nasal lesions developed 2 years later . This chronic fungal infection is typically difficult to cure, and relapses are common . After treatment with 2.5 g of amphotericin B and a 3-year course of triple sulfa, our patient remained free of disease during 12 years of follow-up. J Med Vet Mycol, 1986 Jun, 24(3), 203 - 10 Ultrastructure of spore formation in Paracoccidioides brasiliensis; San-Blas F; Chlamydospores and arthrospores are produced by the mycelial phase of Paracoccidioides brasiliensis in submerged cultures at 23 degrees C . Arthrospores are formed by extrusion in specialized, sporogenous hyphae . The absence of any unique morphological characteristic in chlamydospores and arthrospores discards the use of spore morphology as a taxonomic criterion. J Med Vet Mycol, 1986 Jun, 24(3), 193 - 202 Effect of papulacandin B on glucan synthesis in Paracoccidioides brasiliensis; Davila T et al.; Papulacandin B, an inhibitor of beta-glucan synthesis in some fungi, was tested on both morphological phases of Paracoccidioides brasiliensis . In vivo, the antibiotic did not affect yeast morphology or growth but it inhibited mycelial growth and yeast----mycelium transformation . Increase of alpha-glucan and decrease of beta-glucan synthesis was also observed in the fungal cell wall of the mycelial form after addition of papulacandin B . Synthesis in vitro of beta-glucan was partially substituted by the synthesis of an amylase-sensitive glucan. J Med Vet Mycol, 1986 Jun, 24(3), 243 - 5 Effect of nucleotides on glucan synthesis in Paracoccidioides brasiliensis; San-Blas G et al.; The activity of Paracoccidioides brasiliensis glucan synthetase was partially inhibited by guanosine 5'-triphosphate, adenosine 3'5'-phosphate and adenosine 5'-triphosphate . This inhibition was more pronounced in the mycelial system than in the yeast one, being higher at 23 degrees C than at 37 degrees C . Addition of ethene diamine tetracetic acid to the incubation mixture inhibited partially the enzymatic activity in mycelial preparations but stimulated it in the yeast system. Ann Inst Pasteur Immunol, 1986 Mar-Apr, 137C(2), 127 - 41 Experimental paracoccidioidomycosis in high and low antibody-producer mice . I.--Evolution of the disease, its correlation with the humoral immune response and the patterns of tissue lesions; Carvalhaes MS et al.; High (H) and low (L) responder mice selected for their capacity to produce antibody against flagellar antigens of Salmonellae sp . were infected i.p . with 10(6) L forms of Paracoccidioides brasiliensis, strain 18 . In H mice, the mortality ratio was 50%; the splenic index was high at the onset of infection (1.0), decreasing to normal levels after 30 days (0.45), with antibody titres such as 4-5 log2 . In L mice, the mortality was 87.5%, the splenic index was above 0.6 and the antibody titres after 30 days were below 2 log2 . In L mice, granulomas containing a high number of fungi, epithelioid cells, macrophages and a few polymorphonuclear cells were found . In H mice, focal or diffuse infiltrate of mononuclear cells with few or even the absence of fungi was seen . The passive transfer of immune ascitic fluid to L mice induced a reduction in the number of granulomas and fungi in the lesions. Mycopathologia, 1986 Mar, 93(3), 155 - 61 Ultrastructure of lymphocytes from patients with paracoccidioidomycosis in the lymphocyte transformation test by phytohemagglutinin; Da Costa JC et al.; The morphology and ultrastructure of peripheral blood lymphocytes from patients with paracoccidioidomycosis (PCM) and from unaffected individuals (controls) were studied before and after Ficoll-Hypaque separation and at the end of culture, stimulated with phytohemagglutinin . Patient lymphocytes were cultured in medium with autologous plasma (from the patient himself) and with homologous plasma (from an unaffected donor), while donor lymphocytes were cultured in medium with plasma from a patient or with plasma from the donor himself . The Ficoll-Hypaque mixture caused no morphological or ultrastructural changes in the lymphocytes of patients or of unaffected donors . Patient lymphocytes cultured in medium with autologous plasma showed different degrees of cytoplasmic and nuclear alterations, such as organelle dissolution, vacuoles, amorphous masses, deformed nuclei, and absence of nucleoli . Lymphocytes from control individuals cultured in patient plasma also showed ultrastructural alterations, though they were less marked, and a reduced number of 'blasts' . Patient lymphocytes cultured in medium with homologous plasma (from a control individual) showed a morphology similar to that of lymphocytes from control individuals cultured in medium with their own plasma, although with a lower number of 'blasts' . On the basis of the results obtained using that methodology, we draw the following conclusions: separation by Ficoll-Hypaque does not seem to alter the ultrastructure of patient or donor lymphocytes; patients with diffuse PCM and more markedly impaired general condition can exhibit lymphocytes with morphological and ultrastructural alterations capable of affecting their biological systems and functionality.(ABSTRACT TRUNCATED AT 250 WORDS) J Med Vet Mycol, 1986 Feb, 24(1), 77 - 9 Comparison between magnetic enzyme-linked immunosorbent assay (MELISA) and complement fixation test (CF) in the diagnosis of paracoccidioidomycosis; Pires de Camargo Z et al.; MELISA and CF were compared using sera from paracoccidioidomycosis patients before treatment and patients undergoing antimycotic treatment . With MELISA it was possible to distinguish different antibody levels in both groups of patients whereas such distinction was not observed by using CF tests . MELISA is thus an advantageous alternative to CF in the diagnosis of paracoccidioidomycosis, including the possibility of testing sera with anticomplementary activity. Mycopathologia, 1986 Jan, 93(1), 55 - 9 Paracoccidioidomycosis in a four-year-old boy; Bittencourt AL et al.; A case of fatal, generalized paracoccidioidomycosis is described in a four-year-old urban dwelling child . Marked lymphadenopathy, hepatosplenomegaly and an abdominal mass were the main clinical manifestations . The diagnosis was established by histopathological studies and culture . The authors comment on the rarity of this infection in children less than 7 years of age and on the importance of considering this pathology in the differential diagnosis of malignant non-Hodgkin lymphoma and tuberculosis, in children. Arq Gastroenterol, 1986 Jan-Mar, 23(1), 21 - 5 {Endoscopic evaluation of the involvement of the esophagus, stomach and duodenum in human paracoccidioidomycosis}; Martinez R et al.; The upper gastrointestinal tract was investigated endoscopically in 30 patients with paracoccidioidomycosis . Esophagus, stomach and duodenum showed, respectivelly, 40%, 53% and 43% of endoscopic alterations . The histopathological examination of biopsy tissue revealed no specific lesions in esophagus and stomach, but P . brasiliensis was observed in three cases of duodenal lesions: two cases with mucosal diffuse erosions and one case of duodenal polyp . It is concluded that duodenal paracoccidioidomycosis is not rare and could be revealed by endoscopic examination in patients with disseminated disease. Braz J Med Biol Res, 1986, 19(2), 241 - 7 Complement-mediated-lysis detection of antibodies in paracoccidioidomycosis: a preliminary study; Nogueira ME et al.; The objective of this study was to detect the presence of antibodies by the complement-mediated lysis test in patients with paracoccidioidomycosis, before and after treatment, and to correlate them with the clinical form of the disease and with the levels of precipitin and fluorescent anti-P . brasiliensis antibodies . Eighty percent of sera from 15 untreated paracoccidioidomycosis patients showed positive lytic activity indices (greater than or equal to 15%), as opposed to 50% of sera from 24 treated patients . Sera from 29 of 30 control group blood donors showed 0 to 14% lysis . No correlation was observed between lytic antibody levels and precipitin titers or anti-P . brasiliensis total Ig and IgM antibody titers, either in the untreated or treated patient group . Anti-P . brasiliensis lytic antibodies were detected in various clinical forms of paracoccidioidomycosis . This is the first study using living forms of the fungus to detect anti-P . brasiliensis antibodies and opens the possibility of using the lytic antibodies as indicators of active disease. Infect Immun, 1986 Jan, 51(1), 199 - 203 Estradiol-binding proteins from mycelial and yeast-form cultures of Paracoccidioides brasiliensis; Stover EP et al.; Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis, causes disease much more frequently in men than it does in women, suggesting that the hormonal milieu of the host might influence P . brasiliensis pathogenicity . We recently demonstrated that cytosol from yeast cultures of P . brasiliensis contains a high-affinity, low-capacity, tritiated 17 beta-estradiol {( 3H}estradiol)-binding protein . Estradiol and, to a lesser degree, diethylstilbestrol (DES), inhibited the transformation of P . brasiliensis cultures from the mycelial to the yeast form, an event critical to the establishment of infection . Our current studies demonstrated a somewhat higher affinity (apparent dissociation constant {Kd}, approximately equal to 6 to 12 nM) of the estrogen-binding protein for {3H}estradiol than was previously described for yeast cytosol . The presence of both high- and low-affinity estrogen-binding sites in yeast-form P . brasiliensis cytosol was detected after warming the cytosol to 37 degrees C . The high-affinity protein was labile to further heating (56 degrees C), although the low-affinity protein was stable . Additional experiments demonstrated the presence of an estrogen-binding protein in cytosol prepared from mycelial-form P . brasiliensis . This estrogen-binding protein had a slightly lower affinity for {3H}estradiol (Kd approximately equal to 13 nM), and its cytosol contained somewhat fewer binding sites (approximately equal to 78 fmol/mg of protein) than did yeast-form P . brasiliensis cytosol . Of particular interest was the finding that DES, a weak competitor for {3H}estradiol binding in yeast cytosol, displaced {3H}estradiol from the mycelial-form binding moiety . DES had a 50- to 100-fold-lower affinity for the {3H}estradiol-binding protein than did estradiol, consistent with its lower bioactivity in the mycelial-to-yeast-form transformation studies . The current results lend further support to our hypothesis that endogenous estrogens in the host, acting through the cytosol binding protein in the fungus, inhibit mycelial-to-yeast-form transformation, thus explaining the resistance of women to paracoccidioidomycosis. Infection, 1986 Jan-Feb, 14(1), 22 - 6 Adrenal function in paracoccidioidomycosis: a prospective study in patients before and after ketoconazole therapy; Abad A et al.; The adrenal gland functional reserve was studied in a group of 22 patients with active paracoccidioidomycosis before therapy and in 18 of the same patients after termination of six months of ketoconazole treatment . 22 control subjects were also tested . Serum cortisol was measured before and after i.v . infusion of 250 micrograms of corticotropin given over a period of two hours . Basal cortisol levels were subnormal in only one patients before treatment and in four of 18 patients after therapy . Overt Addison's disease was found in 14% of the patients before treatment . However, corticotropin stimulation revealed diminished adrenal reserve in 23% of patients before, and in 44% of the patients after treatment . Although decreased adrenal cortex function after therapy may be influenced by ketoconazole, more studies are needed to determine the role of this agent after prolonged use . The high frequency of subclinical adrenal failure in paracoccidioidomycosis should alert clinicians in charge of such patients, should they face physiological stress. Sabouraudia, 1985 Dec, 23(6), 443 - 6 Scanning electron microscopic studies of Paracoccidioides brasiliensis in the yeast phase; Minguetti G et al.; Scanning electron microscopy of four different Paracoccidioides brasiliensis isolates in the yeast phase revealed that mother cells generating multiple, spherically shaped buds may be firmly or tenuously associated with their progeny whereas elongated buds remain attached to the mother cell through stem-like structures and may represent early stages of hypha formation . The yeast cell surfaces were covered with a delicate network of microfibrillar components. Sabouraudia, 1985 Dec, 23(6), 407 - 14 Characteristics of the conidia produced by the mycelial form of Paracoccidioides brasiliensis; Bustamante-Simon B et al.; The sporulation capacities of the mycelial form of Paracoccidioides brasiliensis were determined . Five different culture media were used and four human isolates studied . Conidia were produced in three agar media, namely water-agar, glucose-salts and yeast-extract . Corn meal and Sabouraud dextrose agars failed to induce sporulation . Various types of spores were characterized with peculiar bulging arthroconidia and single-celled, pear-shaped conidia predominating . The size of these conidia varied from 3.6 to 4.6 micron in length . It is concluded that the mycelial form of P . brasiliensis produces characteristic spores if the proper culture media are employed. Mycopathologia, 1985 Dec, 92(3), 179 - 88 Pathology of the human pulmonary paracoccidioidomycosis; Tuder RM et al.; Lungs of twelve patients with chronic paracoccidioidomycosis (Pb) were studied in an attempt to understand the pathogenesis of the pulmonary disease . Ribbons of the lung parenchyma including the hilar region and directed towards apical, basal and lateral regions were subdivided into sections from the hilar, intermediate and peripheral segments . The following histopathological reactions directly or indirectly related to P . brasiliensis were described and analysed in relation to the number of slides studied and the pulmonary region involved: pneumonic reaction; early granulomatous formation; mature and healed granulomata; mixed pattern (early and mature granuloma in the same pulmonary area visualized in the slide); pulmonary fibrosis . It was concluded that chronic pulmonary Pb is a recurrent disease affecting equally both lungs . Fibrosis was connected mainly with the progressive evolution of the granulomata towards cicatrization and to a lesser degree probably to a direct induction by the fungi . Based chiefly on the tendency of the fibrosis to run around bronchi and to make up septa interconnecting bronchi and vessels it was hipothesized that these findings were the result of a previous chronic specific lymphangitis by the fungi . Hilar fibrosis would be the result of this lymphangitis and/or of the progression of the specific granulomatous reaction seen in the hilar lymph nodes . Non specific forms of arteritis and areas of destructive emphysema related to granulomatous inflammation and fibrosis were described . Three cases developed pulmonary hypertension. Mycopathologia, 1985 Dec, 92(3), 173 - 8 In vivo and in vitro characteristics of six Paracoccidioides brasiliensis strains; Kashino SS et al.; The yeast-like forms of six P . brasiliensis strains were characterized and compared using in vitro (growth curve determination) and in vivo (pathogenicity to sensitive inbred mice) criteria . Strains Pb 18 and Pb 265 which behaved similarly in vitro, showing low counts of fungi and long mean generation times, were respectively the most and the least pathogenic strains . Strains Pb 2052 and IVIC Pb 267, which grow abundantly in vitro were, respectively virulent and avirulent . Strains Pb SN and IVIC Pb 9 behaved similarly both in vitro and in vivo displaying an intermediate pattern of virulence and growing conditions. Mycopathologia, 1985 Nov, 92(2), 115 - 20 Cyclic adenosine 3',5' monophosphate (cAMP) and dimorphism in the pathogenic fungus Paracoccidioides brasiliensis; Paris S et al.; Exogenous cAMP or its analogs inhibit the mycelium transformation of yeast and induce bulging of the apex of mycelia . But intracellular cAMP levels of yeast and mycelial cells are not significantly different. Br J Exp Pathol, 1985 Oct, 66(5), 585 - 94 Susceptibility and resistance of inbred mice to Paracoccidioides brasiliensis; Calich VL et al.; Nine different inbred strains of mice inoculated intraperitoneally with yeast cells of Paracoccidioides brasiliensis showed significantly varying patterns of susceptibility . The A/SN strain was found to be the most resistant, while BIOD2/nSn, BIO.A and BIOD2/oSn the most susceptible strains . These susceptibility differences were not dependent on the size of challenge inocula and sex of animals . All strains studied showed a mean survival time proportional to the size of inocula used . Although almost all infected male mice presented a shorter survival time when compared with females, significant mortality differences between sexes were found only in two of the strains studied, namely BALB/c and BIOD2/nSn . The H-2 region did not influence the susceptibility pattern since the A/SN and BIO.A strains share the same H-2 haplotype and were respectively highly resistant and susceptible to P . brasiliensis . Furthermore, the presence of C5 and unresponsiveness to lipopolysaccharide had no influence on the mortality data observed . Specific antibodies were detected only in a small number of animals and titres were consistently low, appearing later in the resistant (A/SN) than in a susceptible strain (BIO.A) . Omentum, spleen and liver were the most affected organs in both strains, but the susceptible mice had more granulomatous lesions and earlier dissemination of the fungus. Sabouraudia, 1985 Oct, 23(5), 323 - 34 The ecology of Paracoccidioides brasiliensis: a puzzle still unsolved; Restrepo A; Some aspects pertaining to the ecology of the dimorphic fungus, Paracoccidioides brasiliensis, are reviewed . The available facts concerning the interactions among the only known host (man), the environment (limited to certain Latin-American countries) and the parasite (with an unknown habitat), are analysed . Efforts are made to detect clue circumstances which may lead to discovery of the fungus micro-niche . An analysis of P . brasiliensis mycelial form reveals that such a form has the required capabilities to be the natural infectious form . Its requirements for a moist environment in vitro as well as the high relative humidity predominating in the heart of the endemic areas point towards the possibility of an aquatic--or at least, an extremely humid--habitat for P . brasiliensis. J Trop Med Hyg, 1985 Oct, 88(5), 295 - 9 Treatment of paracoccidioidomycosis with itraconazole in a murine model; McEwen JG et al.; A new triazole, itraconazole, was studied as oral therapy of paracoccidioidomycosis in a murine model . The Paracoccidioides brasiliensis isolate, susceptible to itraconazole in vitro, was given by intranasal challenge, producing acute pulmonary and disseminated disease . Therapy was given twice daily over 4 weeks, and animals observed over 2 months . The infection was lethal for 70-80% of controls (untreated or polyethylene glycol diluent), whereas all treated animals, given 10-200 mg kg-1 day-1, survived . Itraconazole was ineffective in eradicating lung disease in survivors, though effective in treatment of disseminated sites . Since the highest doses did not give a better response than the lower doses, pharmacokinetic studies were performed . These showed irregular curves and small increases in peak serum concentrations and total area under the serum concentration-time curves, which were not proportional to the dose . This non-linearity appears to be best explained by poor absorption . Itraconazole, from these studies, appears to have promise for the therapy of human paracoccidioidomycosis but possibly with a different formulation. J Clin Invest, 1985 Oct, 76(4), 1418 - 26 Monoclonal antibodies against complement 3 neoantigens for detection of immune complexes and complement activation . Relationship between immune complex levels, state of C3, and numbers of receptors for C3b; Aguado MT et al.; C3-bearing immune complexes and C3 activation products were detected by using two monoclonal antibodies, one specific for a neoantigenic determinant on C3c and the other for C3d . To quantitate immune complexes, the anti-C3c or anti-C3d antibodies were fixed to microtiter plates and reacted with test plasma . The binding of C3-bearing immune complexes in this plasma was then measured with radioisotope- or enzyme-labeled anti-human IgG . To test for C3 breakdown products, solid-phase monoclonal antibody to the C3d neoantigen was reacted with EDTA-plasma samples, and fixed iC3b or C3d was measured with a polyclonal anti-C3 antibody . Patients with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome, and paracoccidioidomycosis were found to contain immune complexes bearing C3b/iC3b or C3d . In most conditions, there were more C3d-containing immune complexes than C3b/iC3b . Although CR1 (C3b receptors) rapidly converted immune complex-bound iC3b to C3dg/C3d and lupus patients had reduced CR1, no correlation between the state of C3 on circulating immune complexes or levels of immune complexes and CR1 numbers was seen . However, levels of C3-fixing ICs correlated with levels of C3 activation products . This assay system with monoclonal antibodies to neoantigens expressed on activated, but not native, C3 provides sensitive and specific means for detecting and classifying C3-fixing immune complexes and for assessing C3 activation. Eur J Epidemiol, 1985 Sep, 1(3), 160 - 5 Imported paracoccidioidomycosis: a public health problem in non-endemic areas; Ajello L et al.; Diagnosis of paracoccidioidomycosis in an immigrant who had returned to Italy following a long sojourn in Venezuela prompted a review of imported cases of this Latin American disease in nonendemic countries . Forty-two such instances of well-documented paracoccidioidomycosis were complied . Among these, eleven individuals had arrived in nonendemic countries with active symptomatic infections, fifteen others were first suspected of having tuberculosis, and four each were considered to have blastomycosis caused by Blastomyces dermatitidis and carcinomas . Three individuals were considered to have Wegener's granulomatosis or blastomycosis . Two other patients were treated for syphilis before being diagnosed as having paracoccidioidomycosis . A striking feature of most of these cases was the long asymptomatic period following initial infection . The dormant periods ranged form four months to 60 years with an average duration of 14 years . The need to question patients about travel to or residency in foreign countries is emphasized, along with the necessity to include the mycoses in differential diagnoses . Three reported cases, all from Africa with no history of travel to the endemic areas of the New World, were considered to be doubtful . In one of these, Russell bodies apparently had been mistaken for the tissue-form cells of Paracoccidioides brasiliensis.(ABSTRACT TRUNCATED AT 250 WORDS) Mycopathologia, 1985 Aug, 91(2), 117 - 9 Multiple paracoccidioidomas simulating Wegener's granulomatosis; Severo LC et al.; Five cases of paracoccidioidomas are reviewed . One case with multiple coin-lesions simulating Wegener's granulomatosis is described. Sabouraudia, 1985 Aug, 23(4), 245 - 51 A novel method for estimating killing ability and digestion of Paracoccidioides brasiliensis by phagocytic cells in vitro; Goihman-Yahr M et al.; We describe a novel method by which phagocytosis, digestion and killing of Paracoccidioides brasiliensis yeast cells by polymorphonuclear leukocytes or other phagocytic cells may be estimated simultaneously . Suspensions of P . brasiliensis (yeast-like phase) were sonicated, counted and incubated at 37 degrees C with known numbers of phagocytes . Control preparations contained no phagocytic cells . At given intervals samples were incorporated into gelatin nutrient medium and droplets of the mixtures were incubated at room temperature . Live yeast-like P . brasiliensis germinate in vitro and produce filaments . After incubation, droplets may be melted and examined under phase contrast optics, or the cells may be washed and stained by a variation of Papanicolaou's method . Digested P . brasiliensis, intact but non-germinating yeasts and filamented (viable) yeasts may be identified and counted . Killing and digestive abilities of phagocytes may be estimated by the difference between values obtained from phagocyte-containing and control preparations. Hautarzt, 1985 Jul, 36(7), 408 - 11 {Paracoccidioidomycosis, an imported tropical disease}; Brauninger W et al.; Tropical mycoses are very rare diseases in this country . To date there have only been two published observations of paracoccidioidomycosis in the Federal Republic of Germany . In these rare cases the diagnosis is often delayed because paracoccidioidomycosis imitates frequently appearing and well-known diseases like tuberculosis or sarcoidosis . The diagnostic and therapeutic aspects are illustrated in a recently observed patient from Peru . Therapy consisted of ketoconazole 400 mg/day orally administered with good results and only transient side effects. Mem Inst Oswaldo Cruz, 1985 Jul-Sep, 80(3), 301 - 5 {Production and standardization of Paracoccidioides brasiliensis, Histoplasma capsulatum and Aspergillus fumigatus antigens to be used in immunodiagnosis . Comparison between immunodiffusion and immunoelectrophoresis}; Ferreira-da-Cruz MF et al.; Soluble antigens (Ag) from Paracoccidioides brasiliensis, Histoplasma capsulatum and Aspergillus fumigatus were prepared and standardized by double immunodiffusion (DID) and immunoelectroosmophoresis (IEOP) . No difference in sensitivity was observed between the two techniques; 100% of standard patient sera were positive with P . brasiliensis and A . fumigatus Ag and 83.3% were positive with H . capsulatum Ag . The specificity of the tests was verified testing 96 sera from patients with paracoccidioidomycosis, histoplasmosis, systemic candidiasis, sporotrichosis, tuberculosis, lung cancer, visceral or cutaneous leishmaniasis and 18 sera from healthy individuals . All the three antigens were 100% specific with the DID (using the identification pattern indicated by the confluence of test serum with standard serum precipitin lines as a positive criterium) . However in the IEOP, the specificity varied with each Ag . Positive reactions with P . brasiliensis Ag were observed in 16.7% of histoplasmosis sera and in 10% of cutaneous leishmaniasis sera . On the other hand 31.8% of paracoccidioidomycosis and 10% of cutaneous leishmaniasis sera reacted with H . capsulatum Ag . The high sensitivity and specificity of the DID test, its easy reproducibility and low cost, led us to consider it highly appropriate as a routine procedure for the screening of patients with respiratory infections. J Clin Microbiol, 1985 Jul, 22(1), 39 - 43 Preparation and use of cytoplasmic antigens for the serodiagnosis of paracoccidioidomycosis; McGowan KL et al.; A cytoplasmic antigen of Paracoccidioides brasiliensis (strain MTC) prepared from the yeast phase grown in the chemically defined medium of McVeigh and Morton is described . This antigen can be easily prepared, does not vary from lot to lot, and can be lyophilized without loss of activity or potency . In the immunodiffusion test, the cytoplasmic antigen demonstrated a sensitivity of 97% and a specificity of 100% when tested against 218 sera from 139 cases of paracoccidioidomycosis . When 177 sera from patients with fungal diseases other than paracoccidioidomycosis were tested by immunodiffusion, there were no false-positive reactions . In an enzyme-linked immunosorbent assay, the antigen was equally effective in identifying cases, giving a sensitivity of 100% and a specificity of 99% when a 1:640 titer was considered the threshold for clinical significance . Antigenic components in the cytoplasmic extract of P . brasiliensis were examined after fractionation by concanavalin A-Sepharose 4B column chromatography . The fraction of the cytoplasmic antigen that binds to the concanavalin A column is material identical to the specific b1 (antigen 1) precipitin band described by A . Restrepo and L . H . Moncada (Appl . Microbiol . 28:138-144, 1974). J Gen Microbiol, 1985 Jun, 131 ( Pt 6), 1497 - 501 A Paracoccidioides brasiliensis polysaccharide having granuloma-inducing, toxic and macrophage-stimulating activity; Silva CL et al.; The occurrence of a polysaccharide fraction of Paracoccidioides brasiliensis cell wall with toxic, granuloma-inducing and macrophage-stimulating activities was demonstrated . After fractionation of the lipid-extracted wall with 1 M-NaOH, three fractions were obtained: (1) an alkali-insoluble fraction; (2) an alkali-soluble, acid-insoluble fraction and (3) an alkali-soluble, acid-soluble fraction . When the three fractions were injected into mice only fraction (1) was able to induce chronic lung inflammation, causing a marked loss in body weight and death at a dose of 6 mg per animal . Analysis of the stimulation of peritoneal macrophages of mice (measured by cell spreading on glass) after intraperitoneal injection of fraction 1 showed that 75% of the cells were able to spread even 20 d after inoculation. Eur J Epidemiol, 1985 Jun, 1(2), 150 - 2 Paracoccidioidomycosis (South American blastomycosis): a report of an imported case previously diagnosed as tuberculosis; Benoldi D et al.; A case of paracoccidioidomycosis, previously treated for tuberculosis for two years, is reported . Combined treatment with oral ketoconazole and sulfamethoxypyridazine was successful . The problem of a low index of suspicion among physicians for tropical mycoses, which are very rarely observed in Italy, is discussed. J Rheumatol, 1985 Apr, 12(2), 356 - 8 Paracoccidioides brasiliensis arthritis . Report of a case and review of the literature; Castaneda OJ et al.; A case of Paracoccidioides brasiliensis arthritis is presented . Emphasis on early diagnosis and treatment is made . Natives of endemic areas for paracoccidioides could present elsewhere with dissemination of this disease. Sabouraudia, 1985 Apr, 23(2), 85 - 92 Nutritional studies on Paracoccidioides brasiliensis: the role of organic sulfur in dimorphism; Paris S et al.; The nutritional requirements of the mycelial and yeast-like phases of the dimorphic fungus Paracoccidioides brasiliensis, a human pathogen, were investigated . For all nine isolates tested, mycelial cells were prototrophic, whereas yeast-like cells required a sulfur-containing amino acid for growth . Moreover, changing the source of nitrogen greatly affected the morphology of the yeast-like cells. Sabouraudia, 1985 Apr, 23(2), 143 - 6 Bronchoalveolar lavage findings in pulmonary paracoccidioidomycosis; Boscardin RN et al.; Bronchoalveolar fluid cytology from six progressive pulmonary paracoccidioidomycotic patients showed an alveolitis of neutrophilic pattern which was independent of the of the duration of the chronic fungal disease . The percentage of neutrophils in paracoccidioidomycotic alveolitis was higher than in other neutrophilic alveolitis conditions. Sabouraudia, 1985 Apr, 23(2), 101 - 5 Histochemical localization of succinate dehydrogenase in the mitochondria of Paracoccidioides brasiliensis; Campo-Aasen I; The succinate dehydrogenase activity of Paracoccidioides brasiliensis was investigated histochemically by electron microscopy . The reaction product of this enzyme was demonstrated in some membranous structures of organelles interpreted as mitochondria . This enzyme shows very active oxido-reduction in Paracoccidioides brasiliensis mitochondria during, 3, 6, and and 9 days of culture. Sabouraudia, 1985 Feb, 23(1), 7 - 11 Morphogenesis of the mycelium-to-yeast transformation in Paracoccidioides brasiliensis; Salazar ME et al.; The sequential changes observed during the mycelium to yeast transformation in Paracoccidioides brasiliensis were studied microscopically . The mycelial elements produced terminal and intercalary swellings which, later on, became chlamydospore-like structures . These increased in size, acquired a double contour and, finally, gave rise to multiple budding cells . Transformation was asynchronous . During the observation period, multiple budding cells and chlamydospores remained attached to the parent mycelium. Sabouraudia, 1985 Feb, 23(1), 23 - 9 A yeast-derived antigen from Paracoccidioides brasiliensis useful for serologic testing; Restrepo A et al.; Antigens prepared from P . brasiliensis yeast cells subjected to ultrasonic treatment proved reliable in the serological diagnosis of paracoccidioidomycosis . Detection of antibodies was possible in over 90% from paracoccidioidomycosis patients in tests with agar gel immunodiffusion and counterimmunoelectrophoresis . Specificity was high and only histoplasmosis sera produced cross reactions, albeit at a lower frequency (10%) . The new antigens compared favorably to the standard yeast culture filtrate antigen used in the past and they have the advantage of being reproducible . Proper control of proteolysis is required if activity is to be preserved. Br J Exp Pathol, 1985 Feb, 66(1), 57 - 65 PMN chemotactic factor produced by glass-adherent cells in the acute inflammation caused by Paracoccidioides brasiliensis; Calich VL et al.; Intraperitoneal inoculation of BIO.A mice with P . brasiliensis induces an acute inflammatory infiltrate in which 40-50% of the cells are PMN leucocytes . Previous depletion of serotonin, prostaglandin, histamine and complement does not alter the course of inflammation . Complement-derived factors appear to have no active participation in the process since C5-deficient mice depleted or not by Cobra venom factor (CoF) show the same kind of cellular influx . On the other hand, peritoneal cells incubated (6 h) with the fungus release a soluble factor that induces in vivo an active chemotaxis of PMN cells when inoculated i.p . The factor has the following characteristics: a) it is produced by adherent cells; b) it is protein in nature; c) its production is inhibited by incubation of peritoneal cells with 10 micrograms/ml puromycin and d) it has a molecular weight less than 15 000 daltons, as determined by gel filtration through a Sephadex G-75 column. Trans R Soc Trop Med Hyg, 1985, 79(1), 70 - 3 Granulomatous reaction induced by lipids isolated from Paracoccidioides brasiliensis; Silva CL; The possibility that the histological responses produced in paracoccidioidomycosis might be attributed to lipid constituents of cells of Paracoccidioides brasiliensis was investigated . Charcoal particles coated with the lipid extract were prepared and the suspension inoculated intravenously into mice . The lung inflammation was characterized by an intense mononuclear and polymorphonuclear cell infiltrate surrounding the particles from two to eight days after inoculation . Fractionation of lipid extract by preparative thin-layer chromatography allowed the separation of several fractions and it was observed that fractions containing free fatty acids and triglycerides were the most active . The participation of an uncommon fatty acid eliciting an inflammatory reaction is discussed. Mycopathologia, 1985 Jan, 89(1), 19 - 23 Paracoccidioidomycosis: a comparative study of the evolutionary serologic, clinical and radiologic results for patients treated with ketoconazole or amphotericin B plus sulfonamides; Marques SA et al.; A comparative study of two groups of patients with paracoccidioidomycosis was carried out with the objective of comparing the evolutionary serologic, clinical and radiologic results after 6, 12, 15 and 18 months of treatment with ketoconazole (22 patients) or amphotericin B plus sulfonamides (32 patients) . The serologic data analyzed as a whole showed a tendency to sharper drops in antibody titers in the patients treated with ketoconazole . Clinically patients treated with ketoconazole fared better but the differences were not statistically significant . No statistical difference was detected between groups in terms of the results of radiologic evolution. Am J Trop Med Hyg, 1985 Jan, 34(1), 134 - 40 Study of current and new drugs in a murine model of acute paracoccidioidomycosis; Lefler E et al.; A new murine model of acute paracoccidioidomycosis, whose features include pulmonary infection with dissemination, was used to study the efficacy of currently available drugs and new agents which might be useful clinically . Two oral imidazole drugs, ketoconazole (KTZ) and Bay l 9139 (l9); two oral triazoles, Bay n 7133 (n7) and ICI 153,066 (ICI); and two polyenes, amphotericin B (AMB) and N-D-ornithyl-amphotericin B methyl ester, were studied . KTZ was superior to n7 and l9, particularly after a less lethal challenge . The polyenes could diminish dissemination, but had only modest effects on the pulmonary infection; AMB appeared slightly more effective . ICI was the most effective drug studied, approximately 5-10 times more potent than KTZ on a milligram/kg body weight basis; it had marked effects on both pulmonary and disseminated disease . These initial applications of the model to therapeutic evaluation suggest sufficient flexibility and utility, with information obtainable after relatively short experiments. Mycopathologia, 1985 Jan, 89(1), 13 - 7 Serology of paracoccidioidomycosis . I . Evaluation of the indirect immunofluorescent test; Mistreta T et al.; The purposes of the present work were: i) to study the positivity indices and compare titers obtained with the indirect immunofluorescence (II), tube precipitation (TP), complement fixation (CF) and double immunodiffusion on agar gel (ID) tests in the sera of 196 patients with paracoccidioidomycosis before treatment, and ii) to compare the initial titers of II with those obtained 1 year or more after treatment . II was the most sensitive serologic reaction (85.2%), and the positivity indices for CF, ID and TP were 67.7%, 66.0% and 50.0%, respectively . The sera tended to show parallel mean titers in II, CF and TP tests . One year after treatment there was a fall in titers of II in 66.2% of patients . The data, taken as a whole, demonstrate the usefulness of the indirect immunofluorescent test and the importance of using 2 or more serologic tests for the diagnosis and monitoring of patients with paracoccidioidomycosis. Trans R Soc Trop Med Hyg, 1985, 79(6), 765 - 72 Correlation between cell-mediated immunity and clinical forms of paracoccidioidomycosis; Mota NG et al.; Cellular immune response to specific and non-specific stimulants was investigated, both in vivo and in vitro, in 29 healthy controls and in 53 previously untreated patients with the chronic isolated organic form (CIOF), the chronic mixed form (CMF) and the acute progressive form (APF) of paracoccidioidomycosis . The study included skin tests to Paracoccidioides brasiliensis antigen (PbAg) and phytohaemagglutinin (PHA), DNCB sensitization, determination of T lymphocytes and complement rosette-forming cells, lymphocyte transformation and leucocyte migration inhibition tests using PbAg and PHA . Patients displayed staggered cutaneous response to PHA and to PbAg, with marked decrease in intensity in the APF group . DNCB sensitization test and proliferative response of lymphocytes to PHA and PbAg were severely depressed in most of the patients . Leucocyte migration inhibition indices to PbAg were highly positive, while response to PHA was slightly decreased regardless of the clinical form . The number of T lymphocytes was reduced in most of patients and in them the number of complement-rosette forming cells was normal . The distribution of patients according to a suppression index, based in the results of the tests employed, revealed a tendency towards an increased degree of cellular immunosuppression from the least severe (CIOF) to the most severe (APF) clinical form of the disease . On the whole, the present study demonstrated a gamut of immunological reactivity in paracoccidioidomycosis. Mycopathologia, 1984 Dec 30, 88(2-3), 149 - 54 Sex hormones and susceptibility of the rat to paracoccidioidomycosis; Kerr IB et al.; The development of intraperitoneal paracoccidioidomycosis was studied in groups of female and male rats: a) Under normal conditions (intacts), b) After castration and c) After castration but submitted to a treatment with, respectively, testosterone and estradiol . The criterion of susceptibility to infection was based on: 1) Spontaneous mortality of the animals and 2) Number of metastatic pulmonary lesions . The results showed that: the unique deaths and the more severe pulmonary lesions were found among the intact females, representing the animals most susceptible to the infection in these experiments; the intact females showed more numerous lesions than the castrated; the intact males had less lesions than the castrated, and than those castrated which were treated with estradiol. Mycopathologia, 1984 Dec 30, 88(2-3), 141 - 8 The effect of ketoconazole on experimental paracoccidioidomycosis in the Syrian hamster: immunological and histopathological study; Mota NG et al.; The effect of Ketoconazole (KTZ) on the hamster experimental intratesticular paracoccidioidomycosis was studied employing different treatment schedules . KTZ long course treatment beginning at an early stage of the infection was effective in preventing fungal proliferation, dissemination to lymph nodes, spleen and kidneys, and in maintaining low levels of humoral and cellular specific immune responses . KTZ short course treatment starting at an advanced stage of disease resulted in a more severe histopathological picture without significant changes in the immunological profile . The drug prolonged the life span of hamsters infected with Paracoccidioides brasiliensis, but did not prevent mortality . Toxic necrosis of the bone marrow occurred in normal animals receiving 120 mg/kg/day of KTZ but with lower doses no morphologic alterations were observed in heart, lungs, kidneys, adrenals, spleen, liver, intestine or bone marrow. J Med Microbiol, 1984 Dec, 18(3), 423 - 8 Toxic effect of products of oxidative metabolism on the yeast form of Paracoccidioides brasiliensis; McEwen JG et al.; The effectiveness of toxic oxygen metabolites in killing the yeast form of Paracoccidioides brasiliensis (the form that occurs in host tissues) was studied with a fluorescence method in vitro . The two isolates studied were similar in susceptibility and H2O2 alone was lethal with an LD50 of 15-25 mM . The addition of halide (5 X 10(-4) M) augmented the lethality of H2O2 and in that setting H2O2 was c.90% lethal at 5 X 10(-5) M . Killing was most effective in the presence of peroxidase, when only 5 X 10(-6) M H2O2 (a concentration attainable in vivo by phagocytes) was required for a 95% kill . Kinetic studies revealed that toxic concentrations of H2O2 alone or of the H2O2-halide-peroxidase (PPH) system produced significant killing in 1 min; killing was maximal in 15 min . The PPH system was the more rapid in action . The dependence of the PPH killing system on H2O2 was demonstrated by an absence of killing in the presence of catalase . The susceptibility of P . brasiliensis to H2O2 and the PPH system appeared different in some respects from that noted for other dimorphic fungal pathogens . These studies suggest that toxic oxygen metabolites are important in host defence against P . brasiliensis. J Gen Microbiol, 1984 Nov, 130 ( Pt 11), 2797 - 801 Growth characteristics of the yeast phase of Paracoccidioides brasiliensis in a chemically defined medium; McGowan KL et al.; The growth of four clinical strains of Paracoccidioides brasiliensis was investigated using the chemically defined medium of McVeigh and Morton . Emphasis was placed upon controlling conditions of inoculum preparation, age of inoculum used, and the homogeneity of samples used for analysis . The medium was evaluated for its ability to support growth of the yeast phase of P . brasiliensis at 37 degrees C . Cultures were followed for 240 h and growth patterns were determined by measuring optical density, dry weight, nucleic acids and protein . The medium is excellent for growing the yeast phase of P . brasiliensis . The exponential phase lasted an average of 135 h and the stationary phase 72 h; a decline began after 207 h . This defined medium supports abundant growth of the yeast phase of P . brasiliensis and may thus prove useful in the preparation of yeast-phase antigens. Infect Immun, 1984 Nov, 46(2), 346 - 53 Estrogens inhibit mycelium-to-yeast transformation in the fungus Paracoccidioides brasiliensis: implications for resistance of females to paracoccidioidomycosis; Restrepo A et al.; Evidence that disease due to the thermally dimorphic fungus Paracoccidioides brasiliensis occurs post-puberty predominantly in males led us to hypothesize that hormonal factors critically affect its pathogenesis . We show here that estrogens inhibit mycelial- to yeast-form transformation of P . brasiliensis in vitro . Transformation of three isolates was inhibited to 71, 33, and 19% of the control values in the presence of 10(-10), 10(-8), and 10(-6) M 17 beta-estradiol, respectively . The synthetic estrogen diethylstilbestrol was active but less potent than estradiol, whereas testosterone, 17 alpha-estradiol, tamoxifen, and corticosterone were inactive . This function was specifically inhibited, since yeast-to-mycelium transformation, yeast growth, and yeast reproduction by b