Paracocci

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 budding were unaffected by 17 beta-estradiol . Of note is the fact that mycelium-to-yeast transformation occurs as the first step in vivo in the establishment of infection . The cytosol of the three isolates studied possesses a steroid-binding protein which has high affinity for 17 beta-estradiol . We believe that this binding protein represents a P . brasiliensis hormone receptor which can also recognize mammalian estrogens . We hypothesize that the ability of estrogen to decrease or delay mycelium-to-yeast transformation at the initial site of infection contributes to or is responsible for the marked resistance of females, and that the binder described is the molecular site of action.

Pharmacotherapy, 1984 Nov-Dec, 4(6), 343 - 73
Ketoconazole . Mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic use; Van Tyle JH; Ketoconazole is a well-tolerated oral antifungal agent with a broad spectrum of activity in vitro, but in vitro testing has not yet been correlated to in vivo results . In addition, many variables that can alter in vitro test results have been identified . The drug shows effectiveness in the treatment of paracoccidioidomycosis, chronic mucocutaneous candidiasis, oral thrush, coccidioidomycosis and histoplasmosis . It was recently approved for use in blastomycosis . It is not yet approved for use in dermatophyte infections, but a large body of literature exists supporting this application . Ketoconazole has several reported drug interactions, including lower bioavailability with cimetidine, accumulation of cyclosporin during concurrent therapy and a possible disulfiram-like reaction with alcohol . It is highly protein bound to albumin and is extensively metabolized . Dosage adjustment is not required in renal failure . The main side effects are gastrointestinal and occur in 5-10% of the patients . Rare side effects include gynecomastia and hepatotoxicity . The latter is reported to occur in 1 of 12,000 patients . Ketoconazole impairs testosterone synthesis, and therefore it is recommended that administration more than once daily be avoided in men . The usual dosage is 200-400 mg administered once daily . Few comparative or controlled studies have been published thus far . How it compares to amphotericin B is not known . The optimum dosage and the optimum duration of therapy are not established.

Mycopathologia, 1984 Oct 30, 88(1), 31 - 7
Enzyme-linked immunosorbent assay (ELISA) in the paracoccidioidomycosis . Comparison with counterimmunoelectrophoresis and erythro-immunoassay; de Camargo ZP et al.; An enzyme-linked immunosorbent assay (ELISA) for detection and quantification of antibodies anti-Paracoccidioides brasiliensis is described . Polystyrene plates have been used as solid phase to absorb P . brasiliensis metabolic yeast phase antigen . Twenty sera of proven paracoccidioidomycosis, 11 of histoplasmosis due Histoplasma capsulatum, 20 of aspergillosis and 20 human normal sera were tested . Ninety-five percent of the paracoccidioidomycosis sera had O.D . superior to 0.150 (from 0.163 to 2.650) at 1/400 serum dilution . ELISA assay was compared with counterimmunoelectrophoresis and erythro-immunoassay tests; a correlation was observed only with erythro-immunoassay . ELISA test should give new perspectives for the serodiagnosis of paracoccidioidomycosis.

Acta Cytol, 1984 Sep-Oct, 28(5), 571 - 5
Pulmonary cytology in paracoccidioidomycosis; Tani EM et al.; Paracoccidioidomycosis caused by the fungus Paracoccidioides brasiliensis is a common endemic deep mycosis in Brazil and other Latin American countries; the lungs are frequently involved with suppurative and granulomatous inflammation . With the aim of using pulmonary cytology as a diagnostic tool in paracoccidioidomycosis, the cytologic findings in 127 sputa, 4 bronchial washings and 2 bronchial aspirates from 45 patients with the mycosis were reviewed . Smears from all samples were stained by the Shorr and Leishmann techniques . Cell-block preparations stained with hematoxylin and eosin and by the Gomori-Grocott method were available from 115 samples . Most samples (55%) were purulent, 30% were hemorrhagic and 17% were mucous . Polymorphonuclear neutrophils, macrophages and multinucleated giant cells were observed in all cases . P . brasiliensis was identified in samples from 95.5% of the patients, more frequently in the cell-block preparations (93%) than in the smears (57.7%), probably as the consequence of the application of the Gomori-Grocott stain to the former . Epithelioid cells were present in 62.2% and squamous metaplasia of the respiratory epithelium in 51.1% of cases . Cytology of pulmonary samples proved to be a useful diagnostic method for the detection of lung involvement by paracoccidioidomycosis in humans . The accuracy of the method increased with the number of samples examined from each patient.

Int J Dermatol, 1984 Apr, 23(3), 207 - 10
Treatment of superficial and deep-seated mycoses with oral ketoconazole; Conti-Diaz IA et al.; Oral ketoconazole was given to 50 patients, 36 with superficial and 14 with deep-seated mycoses . Satisfactory results were obtained in dermatophytoses, pityriasis versicolor, and chronic mucocutaneous candidiasis . Paracoccidioidomycosis also responded well to ketoconazole therapy . The authors' experience in patients with histoplasmosis and aspergillosis does not make it possible to express a firm view on the efficacy of the drug . Ketoconazole is not the recommended drug for treatment of sporotrichosis.

J Clin Microbiol, 1984 Mar, 19(3), 404 - 7
Rapid and reliable method for production of a specific Paracoccidioides brasiliensis immunodiffusion test antigen; Blumer SO et al.; Previously published methods to produce Paracoccidioides brasiliensis antigens for serological tests have yielded antigens of inconsistent quality and have involved the use of special semisynthetic media and growth periods of 1 to 3 months to yield suitable reagents . A simple procedure that uses commercially available potato glucose agar and either SABHI broth (Difco Laboratories) or Trypticase soy broth (BBL Microbiology Systems) inoculated with the mycelial form of P . brasiliensis consistently yielded high-titer antigens in 2 weeks or less . This new method permits the almost exclusive production of an antigen identical to the specific E antigen described by Yarzabal (Yarzabal et al., Sabouradia 14:275-280, 1976) and the apparently equivalent specific antigen 1 described by Restrepo and Moncada (A . Restrepo and L . H . Moncada, Appl . Microbiol . 28:138-144, 1974) . In the immunodiffusion test, the rapidly produced antigen demonstrated a sensitivity of 90% by detecting antibody in sera from 103 of 114 proven cases of paracoccidioidomycosis . The specificity of this antigen was 100% because none of 139 sera from patients with heterologous mycotic diseases demonstrated diagnostic precipitins against the P . brasiliensis antigen . In the complement fixation tests, the rapidly produced antigen was not as suitable as the one prepared by the method of Restrepo-Moreno and Schneidau (A . Restrepo-Moreno and J . D . Schneidau, Jr., J . Bacteriol . 93:1741-1748, 1967).

Mycopathologia, 1984 Feb 15, 84(2-3), 171 - 80
Effect of levamisole on experimental paracoccidioidomycosis in the Syrian hamster: immunologic and histopathologic correlation; Rezkallah-Iwasso MT et al.; The effect of levamisole (LMS) was studied in hamsters inoculated with live yeast phase culture of Paracoccidioides brasiliensis by intratesticular route . One group started LMS therapy at an early stage of infection (LMS3 group), when the animals were immunocompetent, and another group was treated in a later stage, when the immune response was already depressed (LMS12 group) . As control, one group was not treated . The alterations induced by levamisole were studied by immunologic and histopathologic parameters . Compared to controls, the LMS3 group presented normal levels of cellular immune response and inflammatory reaction characterized by compact epithelioid granuloma during a longer period of time . In addition, this group showed a lower incidence of amyloidosis and lower fungi proliferation in the lesions . In the LMS12 group a transient enhancement was noteworthy of cellular immune response with maintenance of the compact pattern of the epithelioid granuloma as in the LMS3 group; however, the number of fungi and incidence of amyloidosis were similar to controls . The differences between both treated groups may be accounted for by some factors such as host immune competence, timing and total dose of LMS administered . Levamisole may be of value as additional therapy in paracoccidioidomycosis.

Am Rev Respir Dis, 1984 Feb, 129(2), 340 - 2
Paracoccidioidomycosis in the immunosuppressed host: report of a case and review of the literature; Sugar AM et al.; A case of reactivated paracoccidioidomycosis in an immunosuppressed host is described, the first association of this disease with renal transplantation . His presentation and clinical course was similar to the general experience with this mycosis . his response to ketoconazole was delayed when compared with that in non-immunosuppressed patients . Ketoconazole produced a dramatic resolution of all symptoms within 7 months . Serial determinations of paracoccidioides complement fixing antibodies showed falling titers, accurately reflecting his clinical status . Comparisons are made with other endemic mycoses in immunosuppressed patients . More cases of paracoccidioidomycosis in immunosuppressed patients can be expected to occur as immunosuppressive therapy becomes more common in areas endemic for Paracoccidioides brasiliensis, and with current trends in migration and travel.

Arch Microbiol, 1984 Jan, 137(1), 79 - 84
A dissimilatory nitrite reductase in Paracoccus halodenitrificans; Grant MA et al.; Paracoccus halodenitrificans produced a membrane-associated nitrite reductase . Spectrophotometric analysis showed it to be associated with a cd-cytochrome and located on the inner side of the cytoplasmic membrane . When supplied with nitrite, membrane preparations produced nitrous oxide and nitric oxide in different ratios depending on the electron donor employed . The nitrite reductase was maximally active at relatively low concentrations of sodium chloride and remained attached to the membranes at 100 mM sodium chloride.

J Exp Pathol, 1984 Summer, 1(3), 241 - 55
Murine model of paracoccidioidomycosis . Production of fatal acute pulmonary or chronic pulmonary and disseminated disease: immunological and pathological observations; Brummer E et al.; A model of fatal acute pulmonary or chronic pulmonary and disseminated paracoccidioidomycosis was developed by intranasal challenge of young (3-4-week-old) mice with high doses (2.5-10 X 10(7) units) or low doses (0.1-1 X 10(7)) of yeast-phase Paracoccidioides brasiliensis . Fatal acute paracoccidioidomycosis was dose dependent; 10, 5, and 2.5 X 10(7) viable units of P . brasiliensis produced 100%, 66%, and 17% mortality, respectively, within 11 days . The pathologic picture was that of consolidation with a neutrophil infiltrate . Infection of adult (7-8-week-old) mice with even 10 X 10(7) units did not produce acute fatal paracoccidioidomycosis . The model of fatal acute paracoccidioidomycosis lends itself well to studies of therapeutic intervention . Increasing degrees of chronic pulmonary-disseminated paracoccidioidomycosis were produced by pulmonary infection of young mice with 0.1-1 X 10(7) viable units of P . brasiliensis . Although mice in all groups appeared healthy, pathology in lungs, liver, and spleen was evident at 7 and 10 weeks postinfection . Histopathologic observation revealed acinonodular granulomatous inflammation . At 12 weeks postinfection, there was evidence of less pathology, and of clearing of abscesses . In contrast to the pathology produced by 0.1 X 10(7) P . brasiliensis in young mice, no pathology evident on gross examination was produced by a similar dose in adult mice . Immunological evaluations of mice with chronic pulmonary-disseminated disease showed that spleen cells, but not lymph node cells, had significantly depressed blastogenic responses to concanavalin A (ConA) early after infection . However, at 12 weeks postinfection, when pathological examination indicated beginning resolution of infection, spleen cell responses to ConA were normal . The model of chronic disease is of interest for further immunological studies as well.

Sabouraudia, 1984, 22(6), 509 - 11
Effect of temperature on the mycelium to yeast transformation of Paracoccidioides brasiliensis; Patino MM et al.; The influence of temperature on Paracoccidioides brasiliensis mycelium to yeast transformation was studied by sequential microscopic observations of slide cultures . When incubated at temperatures above 28 degrees C, the mycelial elements gradually produced round to oval chlamydospores and later on, exhibited multiple budding . A sizeable proportion of mycelial elements transformed at 34 degrees C; however, multiple budding was important only at 37 degrees C.

Sabouraudia, 1984, 22(6), 477 - 86
Skin and pulmonary models using coated bentonite particles for the study of the inflammation evoked by Paracoccidioides brasiliensis antigens in previously immunized mice; Defaveri J et al.; Bentonite particles coated with polysaccharide antigen or crude soluble antigen of Paracoccidioides brasiliensis were injected intradermally or intravenously in mice . In control animals that were not pre-immunized with P . brasiliensis antigens, coated and uncoated bentonite caused minimal and nonspecific inflammation around the cutaneous injection site or around the bentonite thrombi in small lung vessels after intravenous injection . However, in mice previously immunized with P . brasiliensis antigens, the coated bentonite particles boosted the humoral and cellular immune responses to P . brasiliensis and evoked intense inflammatory reactions . Twelve days after intradermal injection, the inflammatory reaction around the bentonite was rich in neutrophils, macrophages, lymphocytes and plasma cells associated with young granulation tissue . In intravenously injected mice, the pulmonary inflammation was maximal at day 2, and was characterized by a florid neutrophilic and macrophagic cellular infiltration around bentonite thrombi; in some foci, there was incipient organization to mature granuloma . However, in both models, there was no formation of epithelioid granulomata, demonstrating that in paracoccidioidomycosis cellular immunity alone, without the presence of intact micro-organisms, may not be enough for the development of this type of granuloma.

Sabouraudia, 1984, 22(3), 255 - 7
Chemical changes in cell wall structure of five strains of Paracoccidioides brasiliensis; San-Blas G et al.; Differences in cell wall structure of Paracoccidioides brasiliensis strains isolated from localized or disseminated cases of paracoccidioidomycosis and from soil emphasize the importance of standardization if results obtained in different laboratories are to be compared.

Sabouraudia, 1984, 22(4), 291 - 9
Magnetic enzyme-linked immunosorbent assay (MELISA) for determination of specific IgG in paracoccidioidomycosis; de Camargo ZP et al.; A magnetic solid phase enzyme-linked immunosorbent assay (MELISA) for quantification of IgG antibodies to somatic and metabolic antigens of Paracoccidioides brasiliensis was developed . Activation of magnetic polyacrylamide agarose beads with concanavalin A was superior to glutaraldehyde activation, and test sensitivity was higher for somatic than for metabolic antigens . Comparative MELISA, counterimmunoelectrophoresis and erythroimmunoassay tests with sera from 33 proven cases of paracoccidioidomycosis, 14 cases of histoplasmosis and 20 normal human sera showed the MELISA could distinguish antibody levels in paracoccidioidomycosis from those in normal sera; however two sera from histoplasmosis cases cross-reacted in the MELISA . MELISA is a rapid test (5-6 h) and the results suggest it has considerable potential value for assay of anti-P . brasiliensis antibodies.

Trans R Soc Trop Med Hyg, 1984, 78(5), 617 - 21
Serology of paracoccidioidomycosis . II . Correlation between class-specific antibodies and clinical forms of the disease; Biagioni L et al.; Untreated and previously treated patients with paracoccidioidomycosis were studied for: (i) serum levels of total IgG, IgM and IgA immunoglobulins, by radial immunodiffusion and Paracoccidioides brasiliensis (Pb) antibodies, by indirect immunofluorescence; (ii) correlation between their levels with the clinical forms of the disease; (iii) correlation between the serum titres obtained by tube precipitin with those of anti-Pb IgG, IgM and IgA . In the untreated group, serum IgG levels were significantly increased in patients with the more systemic forms of the disease, especially the acute progressive form . Serum IgA levels were significantly increased in all patients with no statistical difference between clinical forms . Serum IgM levels were normal in all patients . Anti-Pb IgG, IgA and IgM were detected in 97.5%, 32.5% and 45.0% of all cases, respectively . There was a sharp tendency towards higher levels of anti-Pb IgG among those with the acute progressive form (83.4%) in relation to the chronic, more localized forms, mixed form (68.0%) and isolated organic form (55.5%) . In the untreated and previously treated group sera, there was positive correlation between the level of anti-Pb IgG and positivity for the tube precipitin test, suggesting that the precipitin-type antibodies are of the IgG class . Broadly, the present data demonstrate a polyclonal activation of the humoral immune system in paracoccidioidomycosis, with a positive relationship between serological results and severity of the disease.

Sabouraudia, 1984, 22(1), 73 - 7
Titration of antibodies to Paracoccidioides brasiliensis by erythro-immunoassay (EIA); de Camargo ZP et al.; The erythro-immunoassay, a new serological procedure in which a hybrid antibody conjugate is able to bind erythrocytes, was used for the titration of antibodies against P . brasiliensis in sera from patients with paracoccidioidomycosis . A peptide-polysaccharide and a lyophilized yeast culture filtrate of P . brasiliensis were used as antigens . Absorption with dead Candida albicans whole cells was necessary to decrease cross reactions observed with heterologous sera . Erythro-immunoassay provides a sensitive system for titration of antibodies in paracoccidioidomycosis with serum dilutions up to 1:102000.

Crit Rev Microbiol, 1984, 11(2), 101 - 27
Molecular aspects of fungal dimorphism; San-Blas G et al.; The approach to this article will be the review of experimental developments achieved in recent years in the fields of biochemistry, molecular biology, ultrastructure, etc . and that have suggested models and hypothesis in order to understand the regulation of the molecular mechanisms involved in fungal differentiation . Since fungal dimorphism has been seen by many investigators as a useful model of differentiation in eukaryotic systems, and also because of the prevalence of dimorphism among human pathogenic fungi, we have considered relevant to review the work done in Mucor, but also in dimorphic pathogenic fungi such as Paracoccidioides brasiliensis, Histoplasma capsulatum, Candida albicans, Blastomyces dermatitidis, and Sporothrix Schenckii . From this point of view, the involvements of cyclic nucleotides, nucleic acid polymerases, synthesis of macromolecules, synthesis of cell wall and less studied factors will be reviewed.

Int J Tissue React, 1984, 6(3), 229 - 31
Comparison of the cell walls of Paracoccidioides loboi and Paracoccidioides brasiliensis by using polysaccharide-binding dyes; Mendes E et al.; Biopsies from patients with Jorge Lobo's disease (keloid blastomycosis) and paracoccidioidomycosis (South American blastomycosis), caused respectively by Paracoccidioides loboi a non-cultivated fungus and Paracoccidioides brasiliensis, were stained with six different dyes having the property of forming complexes with some polysaccharides and oligosaccharides . The cell-walls of both fungi showed similar staining characteristics, suggesting a similar chemical structure . The role of the fungal cell-walls in evasion mechanisms is discussed.

Sabouraudia, 1984, 22(5), 419 - 26
Chronic murine paracoccidioidomycosis: effect of ketoconazole on clearance of Paracoccidioides brasiliensis and immune response; Hoyos GL et al.; In a murine model of chronic pulmonary and disseminated paracoccidioidomycosis, ketoconazole (100 mg kg-1 in 0.3% agar) given by gavage twice daily for 1 or 2 months enabled all mice to clear disseminated Paracoccidioides brasiliensis from the spleen . Clearance of P . brasiliensis from the lungs was more difficult, and was achieved in 60% of the mice treated for 2 months . Sera from agar-treated control mice at days 77 and 103 post-infection demonstrated precipitating antibodies to P . brasiliensis antigens, but sera from ketoconazole-treated mice were precipitin-negative, indicating a favorable prognosis . Delayed hypersensitivity reactions to P . brasiliensis antigens in ketoconazole-treated mice were not significantly greater than in controls; consequently this test correlated less well with response than levels of serum antibody . This is the first use of this animal model of paracoccidioidomycosis to study the effect of antifungal drug protocols on the resolution of the disease . It also demonstrates the utility of this model in addressing clinically relevant questions about this disease and its treatment.

Mycopathologia, 1983 Dec 1, 84(1), 55 - 63
Lymphocyte transformation test in patients with paracoccidioidomycosis; Da Costa JC et al.; The lymphocyte transformation test (LTT) by phytohemagglutinin was carried out on lymphocyte cultures from patients with paracoccidioidomycosis, in medium with autologous plasma (from the patient) or homologous plasma (from an unaffected individual), and lymphocyte cultures from unaffected and apparently normal individuals, in medium with autologous plasma (from the individual) or homologous plasma (from a patient with paracoccidioidomycosis) . Blastogenesis was evaluated morphologically by 'blast' percentage, and the results analyzed according to clinical form of the disease and general condition of the patient . In the medium containing autologous plasma, percentages below the lower limit of the confidence interval for the distribution of the values for apparently normal individuals were encountered more frequently among patients with diffuse extrapulmonary paracoccidioidomycosis and in poor general condition . When the lymphocytes from patients with the disease were cultured in medium containing homologous plasma, blastogenesis increased in most cases . The lymphocytes of unaffected individuals exhibited a lower response more frequently when cultured in medium containing plasma from patients with the disease than when cultured in medium containing their own plasma . These results suggest that existence of factor(s) inhibiting blastogenesis in the plasma of these patients . In addition to such factor(s), an intrinsic lymphocyte defect may also occur in some patients, which might prevent a greater response to phytohemagglutinin even in homologous plasma . Smears of lymphocytes cultured in autologous plasma and obtained from patients, especially those with diffuse extrapulmonary disease and in regular or poor general condition, and smears from most of the controls whose lymphocytes were cultured in the plasma of these patients revealed deeply stained cells with altered morphology and considerably reduced in number.(ABSTRACT TRUNCATED AT 250 WORDS)

Proc Natl Acad Sci U S A, 1983 Dec, 80(24), 7659 - 63
Estradiol binds to a receptor-like cytosol binding protein and initiates a biological response in Paracoccidioides brasiliensis; Loose DS et al.; Paracoccidioidomycosis, a disease caused by Paracoccidioides brasiliensis, which is endemic to Latin America, is much more common in men than women, suggesting a role for hormonal factors . We recently showed that two other yeasts possess steroid binding proteins and postulated that these receptor-like molecules represented a mechanism by which the hormonal milieu of the host might influence an infecting pathogen . Therefore, we examined P . brasiliensis for a sex steroid binding protein . Because tritiated steroids rapidly dissociated from the other fungal binding proteins, we developed a fast binding method with Sephadex G-50 microcolumns speeded by centrifugation . This method detected specific binding of {3H}estradiol in P . brasiliensis cytosol . Other tritiated steroid hormones, including testosterone and corticosterone, failed to exhibit specific binding . Scatchard analysis of {3H}estradiol binding showed an apparent dissociation constant (Kd) of 1.7 X 10(-8) M and a maximal binding capacity (Nmax) of 235 fmol/mg of protein . Susceptibility to trypsin indicated the binding site was protein in nature . The protein had a Stokes radius of approximately equal to 32 A by HPLC exclusion column and a sedimentation coefficient of 4.4 S by sucrose gradient, consistent with an apparent Mr of approximately equal to 60,000 . Competition experiments revealed that estrone, estriol, and progesterone had 25% of the affinity of estradiol, whereas diethylstilbestrol, androgens, and corticosteroids had low affinity . Investigation of steroid hormone actions in P . brasiliensis indicated that estradiol inhibited the fungal transformation from mycelial form to yeast form, the initial step of infection . This suppressive effect was dose-dependent and not found with testosterone . We hypothesize that endogenous estrogens in the host, acting through the cytosol binding protein in the fungus, inhibit mycelial-to-yeast transformation, thus explaining the resistance of women to paracoccidioidomycosis.

Mycopathologia, 1983 Dec 1, 84(1), 49 - 54
A comparison of mycelial filtrate - and yeast lysate - paracoccidioidin in patients with paracoccidioidomycosis; Restrepo A et al.; A cytoplasmic antigen was obtained from P . brasiliensis yeast cells by water lysis and sonication, with the aim of detecting delayed hypersensitivity to the fungus . This antigen was studied in patients with paracoccidioidomycosis (active and inactive), tuberculosis and histoplasmosis as well as in normal individuals, and it was compared with a mycelial filtrate antigen employed in the past for the same purpose . The yeast paracoccidioidin proved superior to the mycelial preparation (62.0 vs 24.1%) in patients with active paracoccidioidomycosis; however, in inactive cases, both preparations gave similar results . The size of the reactions was also comparable for both products . In normal subjects and in patients with tuberculosis, skin reactivity was low (not over 10%) and within the expected range of the area . In contrast, patients with histoplasmosis proved highly reactive to both antigens . These results indicate that the newer paracoccidioidin has advantages over the mycelial product as it detects a higher proportion of reactors and as such, may be helpful in studies aimed at defining areas of endemicity in countries where paracoccidioidomycosis is present.

Mycopathologia, 1983 Nov 25, 83(3), 187 - 9
Spontaneous regression of pulmonary paracoccidioidomycosis . Report of a case; Lopez R et al.; A case of pulmonary paracoccidioidomycosis with spontaneous regression of the roentgenologic lesions, is reported . Regression of lesions took place within ten weeks, with the original infiltrates being replaced by fibrotic lines . The implication of this finding in the pathogenesis of paracoccidioidomycosis is analyzed.

J Gen Microbiol, 1983 Aug, 129 (Pt 8), 2379 - 85
Distribution of a corticosteroid-binding protein in Candida and other fungal genera; Loose DS et al.; Using {3H}corticosterone as a probe, corticosteroid-binding protein (CBP) was detected in eight out of eight isolates of Candida albicans, of both A and B serotypes . The apparent dissociation constant (Kd) in the various isolates ranged between 8 and 19 nM; the binding capacity varied from 122 to over 2400 fmol (mg cytosol protein)-1 . There was no correlation between the amount or affinity of CBP and isolate virulence for murine hosts . Further analysis revealed demonstrable CBP in six out of six Candida species other than C . albicans . One isolate of C . tropicalis has been identified which fails to bind {3H}corticosterone . Saccharomyces cerevisiae, Neurospora crassa and Paracoccidioides brasiliensis also failed to bind {3H}corticosterone . Preliminary attempts were made to determine functions mediated by CBP in Candida, but in vitro growth, phase conversion and glucose oxidation by Candida were unaffected by the addition of a variety of steroid hormones . These data indicate that the presence of CBP in Candida does not correlate with either virulence or serotype . The physiological significance of CBP remains to be determined.

Mycopathologia, 1983 Jun 20, 82(3), 129 - 41
Granuloma formation and killing functions of granuloma in congenitally athymic nude mice infected with Blastomyces dermatitidis and Paracoccidioides brasiliensis; Miyaji M et al.; We did this experiment to clarify the mechanism of granuloma formation and the killing functions of granuloma in nude mice against Blastomyces dermatitidis and Paracoccidioides brasiliensis infections . B . dermatitidis A-295 and P . brasiliensis B-1183 were the cultures used . Congenitally athymic nude (nu/nu) mice and their heterozygous (nu/+) littermates of BALB/c background were the test animals . From culture A-295, 0.1% and 1% cell suspensions (wet weight) were prepared and from culture B-1183 0.2% and 2% cells suspensions were prepared . Ten nu/+ and 10 nu/nu mice were allotted to each of four cell suspensions . For experimental blastomycosis each mouse was inoculated intravenously with 0.2 ml of the cell suspension of A-295 and for experimental paracoccidioidomycosis, with 0.15 ml of the cell suspension of B-1183 . Two mice from each of the four groups were killed at 5, 8, 12, 18 and 25 days after inoculation, and histopathologic sections, stained with H&E or by PAS, were prepared from various internal organs . In the nu/nu mice inoculated with B . dermatitidis A-295 granuloma was formed in the brain tissue after the 12th day . However, mononuclear cells, which formed the granuloma, did not kill the fungal cells, and the fungal cells continued to multiply in the granuloma . On the other hand, in the heart, kidney and fat tissue, their histopathological findings after the 18th day were clumps of fungal cells with slight cell reactions . In these organs the exertion of cell-mediated immunity was necessary for granuloma formation against the fungal infection . In the nu/nu mice infected with P . brasiliensis B-1183, granuloma appeared in the brain and kidney after the 18th day and fungal cells continued to multiply within the granuloma as well as in those inoculated with culture A-295 . These results show that the exertion of cell-mediated immunity plays an important role in the mouse's defense mechanisms against these fungal infections . We assume that the defense mechanisms of immunocompetent mice against B . dermatitidis or P . brasiliensis infection consist chiefly of two steps: in the first step phagocytosis by PMNs occurs and in the second step cell-mediated immunity enters into play.

Chest, 1983 May, 83(5), 827 - 8
Pulmonary function in paracoccidioidomycosis (South American blastomycosis) . An analysis of the obstructive defect; Lemle A et al.; Comparison of the mean results of routine pulmonary function studies of 17 patients with diffuse pulmonary paracoccidioidomycosis (PM) and manifestations of chronic obstructive pulmonary disease (COPD) to those of 17 matched patients with pure COPD showed no significant differences . These findings were interpreted as fresh evidence suggesting that expiratory obstruction in PM may be secondary to underlying COPD . Other evidence to that effect is discussed.

Mycopathologia, 1983 Apr 22, 82(1), 3 - 12
Exoantigen tests for the immunoidentification of fungal cultures; Kaufman L et al.; Exoantigen tests for the immunoidentification of fungal pathogens are playing a new and significant role in the diagnostic laboratory . Properly performed and controlled exoantigen tests lead to rapid, accurate identification of cultures of many fungal pathogens . The tests are particularly valuable in identifying dimorphic pathogens that are difficult to convert or with atypical cultures . We review the value of exoantigen tests for identifying mycelial form fungi: Aspergillus spp . Blastomyces dermatitidis, Coccidioides immitis, Exophiala jeanselmei, Histoplasma spp., Paracoccidioides brasiliensis, Penicillium marneffei, Pseudallescheria boydii, Sporothrix schenckii, Wangiella dermatitidis and certain dermatophytes . We discuss procedures for performing the tests and sources of error.

Sabouraudia, 1983 Mar, 21(1), 35 - 9
Blood groups and HLA antigens in paracoccidioidomycosis; de Restrepo FM et al.; The frequencies of blood groups, Rh and HLA antigens were studied in a series of patients with paracoccidioidomycosis as well as in control subjects . Statistical analysis of the results showed that only 2 antigens (HLA-A9 and HLA-B13) had a significantly increased frequency among patients with paracoccidioidomycosis compared with healthy controls . Among patients with paracoccidioidomycosis antigen HLA-A9 was significantly more prevalent in progressive pulmonary forms of the disease than in patients with extra pulmonary involvement . These observations suggest that HLA-A9 may influence susceptibility to the mycosis as well as its course.

Drug Intell Clin Pharm, 1983 Mar, 17(3), 169 - 74
Ketoconazole; Hume AL et al.; The treatment of most fungal infections is difficult, at best . Antifungal therapy is complicated by the development of resistant organisms and by the toxicity of many agents . Ketoconazole, an orally active imidazole derivative, has been approved by the Food and Drug Administration for the treatment of candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis . At present, there is very little peer review literature on ketoconazole's effectiveness for several of its approved indications . Gastrointestinal side effects account for the majority of reported adverse reactions; however, preliminary evidence suggests that higher dosages of ketoconazole may decrease adrenal steroidogenesis . Currently, ketoconazole 200-400 mg/d is recommended; the duration of therapy remains to be firmly established . Until well-designed clinical trials are completed and ketoconazole's effectiveness is compared to that of established antifungal agents, its use should be limited.

Arch Neurol, 1983 Feb, 40(2), 100 - 2
Paracoccidioidal granulomatosis of the brain; Minguetti G et al.; A patient with South American blastomycosis (paracoccidioidomycosis) was studied using computed tomography (CT), which showed six granulomas in the brain . The patient was treated with amphotericin B and observed by repeated CT scans . Two of the lesions disappeared completely after the first cycle of treatment, and residual images, probably representing granulomas in the cicatricial stage, remained after completion of the treatment.

Am J Med, 1983 Jan 24, 74(1B), 53 - 7
Post-therapy status of paracoccidioidomycosis treated with ketoconazole; Restrepo A et al.; Twenty-four paracoccidioidomycosis patients who completed a course of therapy with ketoconazole were followed for 12 months after treatment, and 10 of these patients were followed for 24 months . Only two of these patients relapsed; the remaining continued in remission . There were no fatalities . Immunologic tests showed decreased antibody activity and increased skin test reactivity to paracoccidioidin in comparison with the results obtained at the end of therapy . These findings indicate that ketoconazole therapy has improved the prognosis of patients with paracoccidioidomycosis.

Am J Med, 1983 Jan 24, 74(1B), 48 - 52
Treatment of paracoccidioidomycosis with ketoconazole: a three-year experience; Restrepo A et al.; The results of ketoconazole therapy in 38 patients with active paracoccidioidomycosis are described . Treatment consisted of a 200 mg tablet a day for 6 months . Evaluation was accomplished by means of a scoring system and the results were as follows: none of the patients worsened during therapy, one was found to be unchanged, five had minor improvement, 330 had major improvement, and there was complete resolution of the pretherapy conditions in 13 . These findings plus the lack of toxicity of the drug and the facility for oral administration, make of ketoconazole a first line drug for the treatment of paracoccidioidomycosis.

Poumon Coeur, 1983, 39(3), 129 - 33
{South American blastomycosis . Apropos of new cases}; Gonzalez Montaner LJ et al.; Twenty-seven cases of South American blastomycosis are reported . Pulmonary lesions predominate and the diagnosis rests on the findings of Paracoccidioides brasiliensis in sputum and tissues . Serological examinations (complement fixation and immunodiffusion) are also useful . Treatment includes sulphonamides, imidazole derivatives and, in cases resistant to these drugs, Amphotericin B . Surgery is limited to abscesses, bone lesions and bronchial stenoses.

Trans R Soc Trop Med Hyg, 1983, 77(2), 181 - 4
Indirect fluorescent test for detection of anti-Paracoccidioides brasiliensis antibodies using coated bentonite particles as antigen; Chamma LG et al.; An indirect fluorescent test was developed for detecting antibodies to Paracoccidioides brasiliensis using bentonite particles as antigen (Bent-IF) . The bentonite particles were coated with P . brasiliensis polysaccharide antigen and tested with sera from paracoccidioidomycosis patients (36 sera), normal blood donors (32 sera) and patients with non-mycotic diseases (29 sera) . The titres given by the positive sera were compared with those of complement fixation (CF), immunodiffusion (ID) and immunofluorescent test using yeast forms of the fungus as antigen (conventional-IF) . All normal blood donors' sera gave a negative Bent-IF, conventional-IF, ID and CF tests . All paracoccidioidomycosis sera were reactive in conventional-IF and gave concordant results in Bent-IF . There was no correlation between CF and Bent-IF titres . 27.6% of sera from patients with non-mycotic diseases gave weak titres in both IF-tests . The present data indicate that the Bent-IF is a sensitive and simple serodiagnostic technique comparable with the conventional P . brasiliensis antibody test.

Med Cutan Ibero Lat Am, 1983, 11(5), 311 - 22
{Paracoccidioidomycosis}; Texeira LA; The author studies the entrances of Pb, the way it spreads through the body, showing charts that demonstrate the value of lympho-hematogenic dissemination.

Immunol Lett, 1983, 7(3), 129 - 33
Paracoccidioidomycosis in silica-treated rats; Kerr IB et al.; An attempt is made to evaluate the importance of macrophages in the early local reaction to infection caused by the fungus Paracoccidioides brasiliensis . With this purpose, an attempt was made to impair macrophagic activity in the site of the fungal inoculum, by means of previous injections of silica . Twenty male rats were intraperitoneally infected with yeast cells of the fungus . Ten of the rats were injected intraperitoneally with silica particles twice, namely 24 and 4 h before the infection . All the animals were killed 4 wk after fungal inoculum . The results showed that the disease was aggravated in rats pre-treated with silica, clearly demonstrated by the 100% metastatic pulmonary involvement, in contrast with only 40% observed in the non-treated controls.

J Bacteriol, 1982 Nov, 152(2), 563 - 6
Effect of detergents on membrane-associated glucan synthetase from Paracoccidioides brasiliensis; San-Blas G et al.; Yeast and mycelial particulate preparations of Paracoccidioides brasiliensis were subjected to the action of several detergents in an attempt to solubilize the glucan synthetase present in these preparations . This was achieved more successfully in the yeast membranes than in the mycelial ones . The enzymatic activity was greatly stimulated in the insoluble fractions upon treatment with some of the detergents used . The results suggest that the yeast and mycelial phases of P . brasiliensis may differ in the structures of their membranes and also in the characteristics of their glucan synthetases.

Immunol Lett, 1982 Sep, 5(3), 151 - 4
Experimental paracoccidioidomycosis in immunosuppressed mice; Kerr IB et al.; Mice were immunosuppressed by means of wholebody irradiation or cyclophosphamide, in order to investigate the influence on the initial phase of infection induced by a strain of the fungus, Paracoccidioides brasiliensis, in the yeast phase and inoculated intraperitoneally . A group of mice was irradiated with 600 rad (cobalt gamma-irradiation) 24 h before infection . Two groups were treated with cyclophosphamide (200 mg/kg intravenously), one two days before, and the other, one day after infection . A control group received the fungus, but no radiation or cyclophosphamide . All animals developed lesions at the site of inoculation . Metastatic lesions were observed in 100% of the animals in the irradiated group, 67% in each of the cyclophosphamide-treated groups and 33% in the control group . These lesions were found both in the liver and lungs, being more numerous in the irradiated group, followed by the cyclophosphamide-treated group in which the drug was given after the infection; they were slight in both viscera in the other cyclophosphamide-treated group and also slight in the liver and absent in the lungs of the controls.

Mycopathologia, 1982 Aug 20, 79(2), 115 - 23
T-cell dysfunction and hyperimmunoglobulinemia E in paracoccidioidomycosis; Arango M et al.; Various aspects of T and B cell mediated immunity were investigated in 20 well documented cases of active (10) or inactive (10) paracoccidioidomycosis (Pcm), as well as in 8 healthy individuals living in the endemic area of the disease . The results confirm previous reports that active Pcm produces diverse grades of depression of T cell mediated immunity . Such T cell dysfunction is not associated with a reduction in the number of peripheral E rosette-forming cells, and the immunodepression is reversed by chemotherapy . Sera from Pcm (active or inactive) patients have significantly increased levels of total IgE, but the actual proportion of IgE antibodies against P . brasiliensis was very low (0.4-0.6%) . The highest levels of total IgE were found in active patients with disease-related immune depression, suggesting that T cell dysfunction might contribute to the excessive IgE production.

Mycopathologia, 1982 Jul 23, 79(1), 7 - 17
Experimental paracoccidioidomycosis in the Syrian hamster . Morphology and correlation of lesions with humoral and cell-mediated immunity; Peracoli MT et al.; Male hamsters (105) received intratesticular injection of suspension of a live yeast phase culture of Paracoccidioides brasiliensis and were sacrificed weekly during 20 weeks . Humoral immunity was studied by the agar-gel immunodiffusion (ID) and indirect immunofluorescence (IF) tests . Cell-mediated immunity was determined by the macrophage migration inhibition test in the presence of phytohemagglutinin (PHA) and Paracoccidioides brasiliensis soluble antigen (PbAg) . The morphology of the lesions was studied in the inoculation site, lymph nodes, lung, liver, spleen and kidneys . Disseminated paracoccidioidomycosis was observed in 100% of the animals after the first week . The lesions were initially made up of fungi surrounded by polymorphonuclear neutrophils and macrophages . Up to the 10th week the majority of the lesions appeared as compact confluent ephitelioid granulomas containing rare large fungi, some showing sings of degeneration . At this time, the specific antibody titers and the cellular immune response to PHA and PbAg were highest . From the 11th week on the granulomas became less compact, edematous with the epithelioid cells loosely arranged . This change was accompanied by an increase in the number of fungi showing reproductive activity and was associated with renal amyloidosis and progressive decline of cellular immune response both to PHA and PbAg . Contrariwise the titers of circulating antibodies were maintained . In the present model, disseminated paracoccidioidomycosis of the hamster was associated with depression of cellular immunity, change in the pattern of the granuloma, intense fungi proliferation and amyloidosis.

J Clin Microbiol, 1982 Jul, 16(1), 209 - 11
Comparison of various techniques for determining viability of Paracoccidioides brasiliensis yeast-form cells; Restrepo A et al.; The viability of Paracoccidioides brasiliensis yeast-form cells was determined by colony-forming units, direct fluorescent staining, and production of germ tubes in slide culture . The first procedure was unreliable and time consuming; the latter two showed better correlation with hemacytometer total cell counts and required significantly less time.

Mycopathologia, 1982 Jun 18, 78(3), 155 - 9
{Paracoccidioidomycosis: apropos of 3 new Uruguayan cases}; Asconeguy FR et al.; Three new Uruguayan paracoccidioidomycosis human cases are presented . Two of them correspond to the disseminated form with metastatic lesions at the oral mucosa; the remaining one, with important pulmonary bilateral lesions corresponds to the pure chronic pulmonary form of the disease which is recognized by the first time in the country . No doubt, these clinical forms will be found much more frequently in the endemic areas of Latin America if serological surveys are developed in the near future.

Sabouraudia, 1982 Jun, 20(2), 159 - 68
Isolation and partial characterization of a growth inhibitor of Paracoccidioides brasiliensis; San-Blas F et al.; A lethal diffusible metabolite excreted by the yeastlike form of Paracoccidioides brasiliensis was isolated, purified, and partially characterized . The chemical structure of this metabolite suggested a relation to the phenol or benzoic acid families . The lethal effect on P . brasiliensis could not be attributed specifically to interference with synthesis of macromolecules, but probably through protein denaturation . This lack of specificity discounts its possible use as an antibiotic.

Antimicrob Agents Chemother, 1982 May, 21(5), 852 - 4
Synergistic interaction of trimethoprim and sulfamethoxazole on Paracoccidioides brasiliensis; Stevens DA et al.; The in vitro interaction of trimethoprim and sulfamethoxazole on clinical isolates of Paracoccidioides brasiliensis was studied . With complete inhibition and a visual endpoint used as the criteria, three of four strains had minimal inhibitory concentrations that indicated resistance to sulfamethoxazole, and all four strains were resistant to trimethoprim . A marked synergism in inhibition was noted with the combination of these drugs against sulfa-resistant strains . A sulfamethoxazole/trimethoprim ratio of 5:1 was the most synergistic . Fifty percent inhibition, determined spectrophotometrically, of the strains could be achieved with sulfamethoxazole alone . In summary, the striking synergy observed suggests that combination chemotherapy with these drugs deserves further study.

Am Rev Respir Dis, 1982 May, 125(5), 563 - 7
Host defense against experimental paracoccidioidomycosis; Robledo MA et al.; An experimental model for the study of paracoccidioidomycosis was established in BALB/c mice . Both normal and athymic nu/nu animals were challenged intraperitoneally and intratracheally with yeastlike cells of Paracoccidioides brasiliensis . After challenge, all immunologically intact (+/+) mice survived, whereas nu/nu mice gradually succumbed . The latter had focal peritoneal, liver, spleen, and lung lesions consisting of P . brasiliensis with inflammation, polymorphonuclear leukocytes, monocytes, and histiocytic reactions, but no granuloma formation . Thymus transplantation heightened resistance of nu/nu mice to P . brasiliensis . These studies indicate that the nu/nu mouse develops progressive lethal paracoccidioidomycosis after intraperitoneal and intratracheal challenge, and that thymus-dependent immune mechanisms mediate host defense.

Sabouraudia, 1982 Mar, 20(1), 51 - 62
Isolation and wall analysis of dimorphic mutants of Paracoccidioides brasiliensis; Hallak J et al.; Nitrosoguanidine treatment of Paracoccidioides brasiliensis strain IVIC Pb73 induced a set of mutants affected in their ability to complete dimorphism . Some did not transform to the typical mycelial form, while others did not grow as yeasts . These mutants were preliminarily characterized by microscopic observations and the study of some of their properties: optimal growth temperature, nutritional requirements, virulence and cell wall analyses . Comparison of these properties allowed the classification of the mutants in 4 functional categories with respect to dimorphism.

Sabouraudia, 1982 Mar, 20(1), 31 - 40
Variability of cell wall composition in Paracoccidioides brasiliensis: a study of two strains; San-Blas G et al.; A human isolate (IVIC Pb73) of paracoccidioides brasiliensis and a mutant strain (IVIC Pb219) derived from Pb73 were studied with regard to their cell wall composition . Differences were found between these strains and the only other strain (IVIC Pb9) previously studied from this point of view . Besides the expected beta-1,3-linkages, beta-1,2-bonds were also found in the alkali-insoluble glucan of both the parental and the mutant strains in the yeast forms, a rather uncommon linkage in fungal glucans . Also, the alkali-insoluble fraction from the mycelial form was composed of glucose (of which a very small proportion occurred as beta-1,3-glucan) plus a high proportion of galactose (about 50%), and some mannose . The alkali-soluble fraction, usually associated with the immunogenic galactomannan in the mycelial form, also had glucose besides galactose and mannose, but was exclusively composed of mannose in the yeastlike form . These results suggest that, as in other fungi, variations in cell wall composition could be expected between strains of P . brasiliensis.

Mycopathologia, 1982 Jan 15, 77(1), 37 - 41
Choroidal granuloma caused by 'Paracoccidioides brasiliensis' . A clinical and angiographic study; Bonomo PP et al.; A 48 year-old-female with a choroidal granuloma presented a systemic picture of paracoccidioidomycosis proven by rhinopharyngeal biopsy . The clinical picture, the differential diagnosis and the therapeutic test are discussed . This is the first time that the fluorescein angiography is described in such cases.

Mycopathologia, 1982 Jan 15, 77(1), 3 - 11
Experimental pulmonary paracoccidioidomycosis in mice: morphology and correlation of lesions with humoral and cellular immune response; Defaveri J et al.; The present paper describes a murine model for pulmonary paracoccidioidomycosis injecting 6 X 10(5) yeast forms of Paracoccidioides brasiliensis (Pb) by the direct intratracheal route . The sequential histopathology of lung and dissemination lesions together with humoral (immunodiffusion test) and cellular immune response (footpad test and macrophage inhibition factor assay - MIF assay) were investigated since the 1st to the 360th day after infection . All infected animal showed pulmonary Pbmycosis up to Day 30; onwards the lesions subsided being found only in one mouse at Day 360 . Dissemination lesions were observed in paratracheal and cervical lymph nodes in 9 out of 68 infected animals . Histologically early lesions were rich in polymorphonuclear cells and evolved to a macrophage desquamative pneumonitis at Day 15 and to typical epithelioid granulomata from Day 30 up to Day 360 . Specific precipitating antibodies were first detected 15 days after infection, peaked from Day 30 to 60 and were not observed at Day 360 . Significant cell-mediated immunity to Pb was noted at Day 15 with the peak reaction at Day 60 and 90 . The intratracheal route represents a highly effective way of infecting mouse with Pb . This experimental pulmonary Pbmycosis is a granulomatous inflammation which courses with specific humoral and cellular immune response . It may be a good tool for further investigation in the pathogenesis and natural history of the disease.

Sabouraudia, 1981 Dec, 19(4), 275 - 86
Ultrastructural studies on the dimorphism of Paracoccidioides brasiliensis, Blastomyces dermatitidis and Histoplasma capsulatum; Kanetsuna F; Whole cells or cell walls of the yeastlike and mycelial forms of Paracoccidioides brasiliensis, Blastomyces dermatitidis and Histoplasma capsulatum were treated successively with sodium hydroxide, beta-1,3-glucanase and pronase . The microfibrils in the insoluble residues, probably composed of chitin, were examined in the electron microscope . In the yeastlike form, tightly interwoven, randomly oriented microfibrils were seen . On the other hand, in the mycelial form, a large portion of microfibrils tended to lie in a more or less longitudinal orientation . A role of chitin in the conversion from the yeastlike form to the mycelial form is discussed.

Sabouraudia, 1981 Dec, 19(4), 301 - 5
Survival of Paracoccidioides brasiliensis yeast cells under microaerophilic conditions; Restrepo A et al.; The ability of P . brasiliensis yeast cells to withstand microaerophilic conditions was investigated in a liquid medium distributed in tall columns in screw-capped tubes . Young cells of three isolates were inoculated on top of the medium, and the tubes were incubated aerobically and anaerobically at 36 degrees C for 28 days . The viability of cells that had sedimented to the bottoms of the tubes was studied by fluorescent microscopy and by their capacity to resume growth when transferred to fresh medium under continuous agitation . The proportion of viable cells in the sediments diminished with time of incubation . However, after 28 days, 27% of the cells were still viable and fully capable of active growth when placed under adequate aeration . On the other hand, drastic reduction of oxygen access elicited an accelerated death rate, with no survival after 7 days of incubation.

Sabouraudia, 1981 Dec, 19(4), 295 - 300
Recovery of Paracoccidioides brasiliensis from a partially calcified lymph node lesion by microaerophilic incubation of liquid media; Restrepo A et al.; Surgical specimens were obtained from a patient who had had life-threatening paracoccidioidomycosis 5 years previously . Residual lesions were found in the mesenteric lymph nodes; there were areas of caseous necrosis separated from the surrounding tissue by a fibrous capsule made of connective tissue . Abundant P . brasiliensis cells, many of which appeared degenerated, were observed in the necrotic material . Primary isolation was possible only under the microaerophilic conditions offered by fluid media kept stationary at 36 degrees C . Cultures in solid media were obtained after serial passages and gradual accommodation of the strain to aerobic incubation . It is apparent that P . brasiliensis yeast cells can become accustomed to reduced oxygen tension in the tissues . In this way, they are able to withstand the passing of time without completely losing their viability.

Z Hautkr, 1981 Oct 1, 56(19), 1290 - 2
{Cutaneous manifestations of tropical deep mycosis (author's transl)}; Salfelder K; The deep mycoses are classified in 5 groups . Paracoccidioidomycosis belongs in the third group, caused by obligatory pathogenic fungi . In most patients, paracoccidioidomycosis is acquired by aspiration.

Mycopathologia, 1981 Aug 7, 75(2), 65 - 74
The gamut of progressive pulmonary paracoccidioidomycosis; Londero AT et al.; Paracoccidioidomycosis is an important Latin American endemy . The lung is the portal of entrance of the infection and the lesions are confined to this organ in, at least, 30 per cent of the progressive cases . Twelve case histories of patients with the progressive pulmonary form are presented in order to illustrate the repetitious clinical manifestations but the large variety of radiological presentations . The mycologic diagnosis is also emphasized.

Hautarzt, 1981 Aug, 32(8), 420 - 2
{Paracoccidioidomycosis in children . Report on 2 patients}; Castro RM et al.; Two clinical cases of paracoccidioidomycosis were described in two children in Sao Paulo, Brazil . Some clinical peculiarities were pointed out with regard to this mycosis in infancy, i.e., its rarity in children, and the absence of lesions in mucous membranes and lungs, which are so frequent in adults.

Am J Med, 1981 Aug, 71(2), 298 - 301
Recovery of adrenal reserve following treatment of disseminated South American blastomycosis; Osa SR et al.; South American blastomycosis commonly involves the adrenal glands as proved in autopsy series, although clinical adrenocortical insufficiency is infrequently suspected . In 1972, an Ecuadorian man was seen with disseminated paracoccidioidomycosis and Addison's disease documented by low basal steroid levels and lack of response to ACTH therapy . The patient has since been treated with a total dose of 4,000 mg of amphotericin B . He discontinued all steroid replacement therapy for two years but remained asymptomatic . Recent evaluation documented improvement in basal steroid production, particularly mineralocorticoids . Adrenal reserve has also been demonstrated by the response of glucocorticoids to ACTH stimulation . This is the first well documented case in which adrenal reserve was recovered following treatment of granulomatous Addison's disease.

Mycopathologia, 1981 May 8, 74(2), 113 - 8
Ultrastructural changes produced by ketoconazole in the yeast-like phase of Paracoccidioides brasiliensis and Histoplasma capsulatum; Negroni de Bonvehi MB et al.; The ultrastructural changes produced by ketoconazole in the yeast-phase of H . capsulatum and P . brasiliensis were studied by means of scanning and transmission electron microscopy . The observed alterations on both fungi were very similar to those induced by the same drug on the ultrastructure of C . albicans . These alterations include surface changes, abnormal membrane proliferation, fatty degeneration of the cytoplasm and lysis of the subcellular organelles . P . brasiliensis seems to be more sensitive to ketoconazole than H . capsulatum, since the necrosis of most of the cells was obtained in the former at a concentration of 0.1 microgram/ml and in the latter at 1 microgram/ml.

Hautarzt, 1981 May, 32(5), 249 - 52
{Paracoccidioidomycosis (South American blastomycosis)}; Azambuja R et al.; Paracoccidioidomycosis (South American blastomycosis) is a severe deep mycosis that begins in the lungs, mouth and pharynx and can affect the whole organism through lymphatic and hematologic dissemination . It is caused by the fungus Paracoccidioides brasiliensis and occurs in warm and humid regions near large forest . The sulfonamides are very active and represent the therapy of choice . Special cases are treated with Amphotericin B.

Mycopathologia, 1981 Apr 10, 74(1), 51 - 4
Early diagnosis and prompt treatment by surgery in Jorge Lobo's disease (keloidal blastomycosis); Baruzzi RG et al.; In 1931 the Brazilian doctor Jorge Lobo examined a patient from the Amazon Basin who had nodular confluent skin lesions over the lumbosacral region and encountered a new fungus pathogenic for man Paracoccidioides loboi . This classification was based on the morphological aspect of the parasite which was very similar to Paracoccidioides brasiliensis the causative agent of a systemic mycosis Paracoccidioidomycosis or South American Blastomycosis . Other authors use the name Loboa loboi . The final determination of the name must await cultivation of the fungus.

Med Cutan Ibero Lat Am, 1981, 9(4), 259 - 74
{Intradermal tests and epidemiologic survey of South American blastomycosis}; Nunes Texeira LA; This paper is part of the author's free-teaching theses presented in 1974, in which he has studied 436 persons not carriers of the B.S.A . and other diseases, resident in Campos, Conceicao de Macabu and Quissama (urban and rural zones) . Tests were applied in these patients by using standardized antigen of polysaccharide of Paracoccidioides brasiliensis of histoplasmine . The author concluded that there has been existence of the B.S.A.-infection which means what is called "INFEKT" . He emphasizes that the epidemiologic researches have important role in the estimation of the incidence of the B.S.A.

Sabouraudia, 1980 Dec, 18(4), 281 - 6
Lipid composition of Paracoccidioides brasiliensis: comparison between the yeast and mycelial forms; Manocha MS; The total lipid extracted from the yeast form of Paracoccidioides brasiliensis was twice as much as from the mycelial form . In both morphological forms neutral lipids were predominant and triglycerides were the greatest single component in the extracts . Relative percentage of phospholipid was higher in Y form than in M form . Phosphatidylcholine was predominant in the former and phosphatidylethanolamine in the latter . Diphosphatidylglycerol was the most unsaturated lipid in both the forms, and in the Y form it was the only individual class of lipid that contained a greater percentage of linoleic than oleic acid . Otherwise, the lipids of Y form, both neutral and polar, were characterized by a greater percentage of oleic acid and those of the M form by the predominance of linoleic acid . Differential distribution of phosphatidylcholine, phosphatidylethanolamine, sterol, oleic and linoleic acid in Y and M forms is interpreted to suggest a possible role of cellular lipid composition in the dimorphic behaviour of P . brasiliensis.

Clin Endocrinol (Oxf), 1980 Dec, 13(6), 553 - 9
Limited adrenal reserve in paracoccidioidomycosis: cortisol and aldosterone responses to 1-24 ACTH; Del Negro G et al.; Adrenal function in twenty-three patients with paracoccidioidomycosis (South American Blastomycosis) has been assessed by measuring the response to adrenocortical stimulation with 1-24 ACTH . Two patients with overt Addison's disease showed very low basal levels and the complete absence of an increase in either cortisol or aldosterone secretion . Six patients showed probable diminished adrenal reserve in terms of cortisol and three patients showed diminished reserve in terms of aldosterone function . These findings indicate an incidence of significant hypoadrenalism in 44% of hospitalized patients with disseminated paracoccidioidomycosis.

Mycopathologia, 1980 Oct 31, 72(2), 75 - 8
Electrophoretic migration of Paracoccidioides brasiliensis specific antigenic fraction; Conti-Diaz IA et al.; Using the technique of immunoelectroosmophoresis-immunodiffusion (IEOP-ID), two antigenic fractions of Paracoccidioides brasiliensis one of them species-specific, produced precipitin bands in both the cathodic and anodic zones . Reactions of complete identity among the bands formed in these zones were demonstrated by a modification of the technique, employing additional wells around the central antigen well . Such bands would correspond to a simple diffusion of the corresponding antigenic fractions rather than to active electrophoretic migration.

Biochemistry, 1980 Oct 14, 19(21), 4727 - 33
Kinetics of oxidation and reduction of high-potential iron-sulfur proteins with nonphysiological reactants; Mizrahi IA et al.; We have investigated the kinetic and equilibrium oxidation-reduction properties of HIPIP's from four sources: Chromatium vinosum, Thiocapsa pfennigii, Rhodopseudomonas gelatinosa, and a paracoccus sp . These studies focused on the interaction of the various HIPIP's and the iron hexacyanides as a function of ionic strength, pH, and temperature . On the basis of the kinetic and equilibrium data obtained and the known structrual properties of the various HIPIP's a number of conclusions concerning the mechanism of electron transfer by HIPIP can be inferred . (1) The oxidation and reduction of HIPIP by the iron hexacyanides show no kinetic complexity due to heterogeneity or changes in rate-limiting step . (2) The kinetic and equilibrium studies (oxidation-reduction potential) are in good agreement, although a rapid binding equilibrium between HIPIP and the iron hexacyanides is possible . (3) The kinetics of oxidation and reduction of the various HIPIP's studied do not correlate with their oxidation-reduction potentials . (4) The electrostatic interactions between a particular HIPIP and the iron hexacyanides appear to be influenced by the charge on the iron-sulfur cluster with specific amino acid side chains playing a significant but limited role in the interactions leading to electron transfer . (5) The iron-sulfur cluster charge is apparently distributed on the surface of the HIPIP molecule through a network of hydrogen bonds . (6) On the basis of an analysis of the known primary and tertiary structure of the HIPIP's studied, it is concluded that peptide backbone carbonyls and amino acid side chains for the amino acid sequence positions 46-49, 63-65, 78-82, 31-34, and 16-17 define the interaction site of HIPIP and the iron hexacyanides irrespective of the HIPIP source . This is a structural region at which the iron-sulfur cluster is near to the protein surface and in this respect resembles the active site in mitochondrial cytochrome c.

Chest, 1980 Oct, 78(4), 650 - 2
Paracoccidioidomycosis presenting as a cavitating pulmonary mass; Agia GA et al.; Paracoccidioidomycosis, a granulomatous fungal infection often termed "South American blastomycosis," has been reported in only 11 patients in the United States to date . All have been male patients who had either traveled to or emigrated from South America . We report the findings in a 24-year-old woman with a solitary cavitating pulmonary mass which was proven to be paracoccidioidomycosis . This uncommon presentation of paracoccidioidomycosis was surgically resected, and no antifungal chemotherapy was instituted . The patient remains well and apparently free of the infection.

Int J Dermatol, 1980 Sep, 19(7), 405 - 8
Treatment of paracoccidioidomycosis, candidiasis, chromomycosis, lobomycosis, and mycetoma with ketoconazole; Cuce LC et al.; The authors present the use of ketoconazole in 27 cases of paracoccidioidomycosis, eight of mycetoma, seven of chromomycosis, four of systemic candidiasis and one of lobomycosis . The drug was administered orally in a dosage of 200 to 400 mg per day within a period of up to 90 days . The results of the treatment for paracoccidioidomycosis were of cicatrization of the cutaneous lesions in three to four weeks in 24 patients and in two, from six to seven weeks . Out of 27 patients, 14 presented pulmonary lesions . The evolution within a 90-day period showed radiological cure in one case, improvement in seven, and unaltered picture in five patients . In one, there was no further control . In the three out of four cases of candidiasis there was clinical and mycological cure and in one case marked improvement . In seven cases of chromomycosis there was marked improvement in two, moderate in four, and slight in one case . There was slight improvement in one case of lobomycosis, and in eight cases of mycetoma moderate improvement in three, slight in three and none in two, but the mycological examinations were still positive . The drug tolerance was excellent.

Mycopathologia, 1980 Aug 29, 72(1), 17 - 9
Small forms and hyphae of paracoccidioides brasiliensis in human tissue; Londero AT et al.; A 53 year-old man had a three-year recurrent respiratory infection . No fungi was detected in sputum examinations . Immunodiffusion test with paracoccidiodin revealed two precipitin bands . Very small forms and hyphae of a fungus were seen on silver methenamine stained serial sections from lung's lesion . P . brasiliensis was identified on the basis of the rare multibudding small forms.

Mycopathologia, 1980 Aug 29, 72(1), 35 - 45
Ketoconazole in paracoccidioidomycosis: efficacy of prolonged oral therapy; Restrepo A et al.; Ketoconazole, a new oral imidazole derivative, was employed for the treatment of five patients with paracoccidioidomycosis . The response was excellent, with objective clinical improvement and healing of both mucocutaneous and pulmonary lesions . Mycological and serological tests, as well as delayed hypersensitivity, were assessed and found to correlate with clinical improvement . Therapy was conducted for 12 months with a dose of 200 mg day in 2 patients; in the remainder the dose was reduced (100 mg day) after the first 6 months and maintained as such for an equal period . No side-effects or toxicity were noted despite prolonged treatment . The advantages of the new therapeutic approach are discussed.

J Clin Microbiol, 1980 Aug, 12(2), 279 - 81
Growth of Paracoccidioides brasiliensis yeast phase in a chemically defined culture medium; Restrepo A et al.; A slight modification of the chemically defined medium of McVeigh and Morton resulted in an excellent substratum for the cultivation of Paracoccidioides brasiliensis yeast phase.

Antimicrob Agents Chemother, 1980 Jul, 18(1), 190 - 4
In vitro susceptibility testing of Paracoccidioides brasiliensis to sulfonamides; Restrepo A et al.; A total of 60 clinical isolates of Paracoccidioides brasiliensis were tested for susceptibility to sulfadiazine and sulfadimethoxyne by the agar dilution technique . A modification of the Mueller-Hinton medium was devised which gave good growth of the yeast form . The minimum inhibitory concentrations for only 51.6% of the isolates were in the range of the recommended blood serum concentration (50 micrograms/ml) . For 6 to 8% of the isolates, the minimum inhibitory concentrations were above 200 micrograms of both sulfadiazine and sulfadimethoxyne per ml . A significant decreases in susceptibility was demonstrated for one isolate obtained from a patient relapsing during sulfonamide therapy.

Rev Infect Dis, 1980 Jul-Aug, 2(4), 643 - 9
Ketoconazole in the treatment of paracoccidioidomycosis and histoplasmosis; Negroni R et al.; Ketoconazole was given orally to 33 patients with paracoccidioidomycosis and 23 with histoplasmosis . There were 55 men and one woman, and ages ranged from 28 to 67 years . Each patient had either the chronic disseminated or the chronic pulmonary form of disease . The diagnosis was established in 54 patients by culture of Paracoccidioides brasiliensis or Histoplasma capsulatum from lesions and in two patients by the clinical picture and results of serologic tests for histoplasmosis . The initial dosage was 400 mg per day . The dosage was reduced to 200 mg when a cure was achieved . The duration of treatment ranged from two to 18 months . Results of treatment were classified as very good (clinical and serologic cure) in 23 (41%) of the patients; good (clinical cure only) in 28 (50%); fair (partial improvement) in one (2%); and poor (no improvement) in three (5%) . The results were not assessable in one patient who did not complete therapy . The three patients who did not respond to treatment had less than or equal to 0.19 microgram of ketoconazole/ml in their blood . The drug was well tolerated, and no side effects were reported.

Rev Infect Dis, 1980 Jul-Aug, 2(4), 633 - 42
Ketoconazole: a new drug for the treatment of paracoccidioidomycosis; Restrepo A et al.; Ketoconazole was administered orally to 13 patients with paracoccidioidomycosis . Therapy consisted of 200 mg per day for periods ranging from three to 12 months . All patients improved markedly, with healing of pulmonary, mucosal, and skin lesions . Patients exhibiting the latter two manifestations began to improve two weeks after therapy, and healing occurred within three months . Pulmonary lesions regressed at a slower pace and healed by fibrosis . Mycologic tests have corroborated the clinical improvement . Adverse effects were not observed; monitoring of renal, hematologic, and hepatic functions did not reveal any abnormalities . Five patients completed a year of therapy and were free of symptoms when therapy was discontinued . Of these patients, four were followed for several months and had no relapses; the fifth patient developed tuberculosis and died . The results indicate that ketoconazole is a safe and effective drug for therapy in the treatment of paracoccidioidomycosis.

Mycopathologia, 1980 Jul 1, 71(2), 73 - 83
Studies on plating efficiency and estimation of viability of suspensions of Paracoccidioides brasiliensis yeast cells; Goihman-Yahr M et al.; Mild sonication was used to obtain single cell suspensions of Paracoccidioides brasiliensis . These cells were intact by microscopic criteria . Direct cell counts in a given inoculum and colony formation on various media were used to determine plating efficiency . Sonicated and nonsonicated cell suspensions were used to study plating efficiency and to estimated viability by means of vital dyes . Methylene blue Erythrosin B, and Janus green were unreliable when used with P . brasiliensis, but vital dyes were accurate when tested with Candida albicans . Acridine orange gave more meaningful results of viability . Estimates of viability, however, changed significantly as a result of relatively minor alterations in the composition of the suspending medium . In initial experiments, the plating efficiency of P . brasiliensis was dismally low . It descended abruptly with increasing dilution of inoculum . Efficiency was much improved if horse serum was added to brain heart infusion plates or if glucose glycine yeast extract (GGY) plates were incubated at room temperature and mycelial colonies were counted . With the technique we report, current plating efficiency of sonicated suspensions is of the order of 25% . Our results and procedures have an important bearing upon those studies concerned with in vitro killing of P . brasiliensis in suspensions or with isolating this fungus from clinical or environmental specimens.

C R Seances Acad Sci D, 1980 May 5, 290(17), 1177 - 9
{Peptide-polysaccharides isolated from the culture medium of the fungus Paracoccidioides brasiliensis pathogenic to man}; Rodriguez V VJ et al.; A peptido-polysaccharide isolated from the culture medium of Paracoccidioides brasiliensis has been studied . The crude product is a mixture of several polysaccharides releasing, by hydrolysis glucose, mannose and galactose . The purified fraction contains mannose (88%) and galactose (12%) . This galactomannan has a molecular weight varying between 4.6.10(4) and 2.6.10(4) . It is associated with a peptide containing four amino-acids.

Allergol Immunopathol (Madr), 1980 May-Jun, 8(3), 185 - 8
Paracoccidioidomycosis, neoplasia and associated infections; Leao RC et al.; A highly significant percentage of malignancy (8.2%) was found in a group of 147 patients with Paracoccidioidomycosis . Tuberculosis was also observed in 19% of this patient group . The possible immune mechanisms involved in this association are discussed.

J Gen Microbiol, 1980 Mar, 117(1), 147 - 54
Lipid composition of Paracoccidioides brasiliensis: possible correlation with virulence of different strains; Manocha MS et al.; The lipid content and composition of four strains of Paracoccidioides brasiliensis were analysed to determine any possible correlation with their virulence for hamsters and mice . Two strains, Pb168 and Pb141, were equal in virulence, Pb9 was slightly virulent and Pb140 was avirulent under the experimental conditions . No correlation was observed between virulence and the total lipid or phospholipid content of the strains . The lipid yield was highest in Pb9 and lowest in Pb168 . Polar lipids were highest in Pb9 and least in Pb140 . Phosphatidylcholine was the dominant phospholipid in all strains but its percentage was lower in the avirulent strain Pb140 . Diphosphatidylglycerol, the least saturated lipid in all strains, was less abundant in Pb140 than in the virulent strains Pb168 and Pb141 . In all four strains, neutral lipids constituted the major fraction of total lipids and triglycerides were the predominant individual lipid class, being more abundant in the avirulent and slightly virulent strains that in the virulent strains . The fatty acid profiles of total lipids and individual lipid classes of neutral and polar lipids obtained from the four strains were similar; however, the individual lipid classes showed patterns of preferential distribution of these fatty acids.

Int Arch Allergy Appl Immunol, 1980, 62(3), 346 - 51
Demonstration and quantification oomycosis; Yarzabal L et al.; Using a radioimmunoassay technique, we have determined the total IgE concentration and specific IgE antibody level against Paracoccidioides brasiliensis in the sera of patients with mycologically confirmed active paracoccidioidcosis . Patients with aspergilloma, or individuals with antibodies against Cadida albicans, and sera of apparently healthy individuals from the endemic area were also examined . The level of total IgE was significantly elevated in 9 out of 10 cases of paracoccidioidomycosis . The mean level of specific IgE against P . brasiliensis was significantly higher in the serum of the patients in comparison with control individuals . The percentage of specific IgE relative to the total varied from 0.38 to 2.28% . The differences between IgE levels in pare other mycoses were statistically significant . Our results suggest a possible involvement of specific IgE antibodies against P . brasiliensis in the immune response of patients with paracoccidioidomycosis . The hyperimmunoglobulinemia E may be related to the T-cell defect that characterizes the severe forms of the disease.

Med Cutan Ibero Lat Am, 1980, 8(4-6), 95 - 100
{Transfer factor in diffuse cutaneous leishmaniasis . Experience with one case}; dos Reis VL et al.; Transfer factor was administered in one case of Diffuse Cutaneous Leishmaniasis ("DCL") with minimal therapeutical results after two courses of ten doses each . The patient was 34-year-old white man, born in the State of Para --Amazon-- region, goldwasher, his disease started 9 years ago and consisted of disseminated papular and nodular lesions, some of them secondarily ulcerated and more closely clustered over the knees elbows and dorsa of the hands . Physical examination was normal except for the skin lesions and a perforation of the nasal septum . Some intradermal tests (Paracoccidiodin, Lepromin and PPD) were positive while the Montenegro (leishmanin) reaction was negative . Increased levels of IgG and IgM were found; IgA was normal even after the treatment . Transfer Factor was obtained from leishmanin positive and PPD strong reactors and the method of preparation is described . By the end of the first ten-doses course, lesions were reduced to dark atrophic residual macules but the histological sections displayed a surprising amount of parasites, predicting unavoidable relapse . For the second series, as the patient refused to be given Amphotericin B he was treated with hot baths and levamisole was administered in a 150 mg daily dosage and 45 days cycles . The leishmanin intradermal test did not became positive after the treatment and this fact is discussed.

Drugs, 1980 Jan, 19(1), 7 - 30
Miconazole: a preliminary review of its therapeutic efficacy in systemic fungal infections; Heel RC et al.; Miconazole is an imidazole antifungal drug which has recently become available for systemic use . Its antifungal activity has been well studied and it is active in vitro against a wide range of fungi . Published and unpublished reports of the use of miconazole in conditions such as systemic or mucocutaneous candidosis, coccidioidomycosis, fungal meningitis, and paracoccidioidomycosis (which seems especially responsive) have often been encouraging, particularly in view of the serious, refractory nature of the conditions treated, but in most areas of use experience is limited . There are few effective drugs available for treating most systemic fungal infections, and if further studies confirm the encouraging results often seen to date, miconazole will be an important addition to the limited choices available for such conditions.

Gut, 1979 Oct, 20(10), 896 - 9
Blastomycosis of the colon resembling clinically ulcerative colitis; Penna FJ; An 8 year old Brazilian girl had an infection, apparently confined to the large intestine, with Paracoccidioides brasiliensis . The symptoms were diarrhoea with fresh blood and mucus, severe malnutrition, and a spastic and ulcerated colon . She is making good progress on co-trimoxazole.

Mycopathologia, 1979 Sep 28, 68(3), 171 - 4
Acute pulmonary paracoccidioidomycosis in an immunosuppressed patient; Severo LC et al.; A case of an acute pulmonary paracoccidioidomycosis following the use of immunosuppressive therapy in a solid cancer patient is reported.

Sabouraudia, 1979 Sep, 17(3), 279 - 85
Liberation of protoplasts from the yeast-like form of Paracoccidioides brasiliensis by enzymatic treatment; Grimaldi de Jimenez G et al.; Spherical and osmotically sensitive protoplasts were released from cultures of the yeast-like form of Paracoccidioides basilienisis strain IVIC Pb9 through the action of a mixture of crude enzyme preparations: alpha and beta-glucanases and chitinase, obtained from culture filtrates of Cladosporium resinae, Basidiomycete QM 806 and Streptomyces sp respectively . The highest efficiency of protoplast liberation was achieved when each crude enzyme preparation was used at 1 mg/ml.

J Clin Microbiol, 1979 Sep, 10(3), 365 - 70
New method for estimating digestion of Paracoccidioides brasiliensis by phagocytic cells in vitro; Goihman-Yahr M et al.; We describe a method by which phagocytosis and digestion of Paracoccidioides brasiliensis yeast cells by polymorphonuclear leukocytes or other phagocytic cells may be estimated . Suspensions of P . brasiliensis in its yeastlike phase were sonicated, counted, and incubated with known numbers of peripheral blood polymorphonuclear leukocytes . At given intervals, cytocentrifuge droplets were stained by a variation of Papanicolaou's method . Stained preparations were examined with phase-contrast optics . Digested organisms showed total or partial disappearance of protoplasm . Green-stained cell walls resisted digestion . The proportion of digested cells as a function of time was estimated.

J Trop Med Hyg, 1979 Aug, 82(8), 173 - 6
A case of paracoccidioidal granuloma in norther Nigeria; Lawande RV et al.; A case of Paracoccidioidal granuloma in Northern Nigeria is presented . The fungus could be cultured and identified as Paracoccidioides brasiliensis . Histology revealed a fungal lesion due to a yeast like organism . The patient responded to long acting Sulphormethoxine (Fanasil) . A variation from the classic histopathological description and association of pustular psoriasiform lesions on the soles with a possibility of 'Id' reaction to the fungus are discussed.

Mycopathologia, 1979 Jul 16, 67(3), 131 - 41
Experimental paracoccidioidomycosis in the Syrian hamster: morphology, ultrastructure and correlation of lesions with presence of specific antigens and serum levels of antibodies; Iabuki K et al.; Male hamsters (134) received intratesticular injection of a live cerebriform culture of Paracoccidioides brasiliensis and were sacrificed from 6 hours up to 123 days onwards . Tissues from testis, lymph nodes, lungs, liver, spleen, kidneys and intestines were examined microscopically; presence of specific antigens was saught in lesions of testis, regional lymph nodes and liver by indirect immunofluorescence (IF); inoculation site lesions were studied electron microscopically and circulating specific antibodies measured by complement fixation and IF tests . Up to 24 hours inoculation site lesions showed fungi surrounded by PMNs; 48 hours latter macrophages accumulated forming loose nodules; epithelioid granulomata appeared after 5 days . Fungi, scarce in early lesions, increased in numbers up to the time when epithelioid granulomata dominated the picture; in young granulomata fungi were abundant and small; older granulomata contained rare, vacuolated fungi . Ultrastructurally the space between fungi and host-cells was larger around reproducing forms decreasing in size as the parasites grew larger and being a virtual slit around old degenerated fungi . Immunofluorescence studies revealed that fungal walls were brightly fluorescent; in early lesions macrophages surrounding fungi or free in the intersticium contained fluorescent antigenic material in the cytoplasm; similar macrophages were observed in draining lymph nodes as early as 18 hours after inoculation, and latter, in macrophage nodules and Kupffer cells in the liver; epithelioid and giant cells appear to block diffusion of antigens, since in epithelioid granulomata fluorescence was limited to fungal walls . Disseminated paracoccidioidomycosis occurred in 100% of animals after day 5 of infection . Besides specific lesions (containing fungi), antigens were identified by immunofluorescence in 'non specific' lesions in the liver (diffuse or nodular Kupffer cell hyperplasia) and in the lymph nodes (histiocytic hyperplasia) . Serum antibodies appeared in low titers, up to day 20, increasing onwards . From day 70 on, titers decreased and lesions changed from confluent epithelioid to loose granulomata infiltrated by PMNs; fungi that before were large and quiescent now were small and in active reproduction . Secondary amyloidosis was present in 85% of the amimals . In the hamster, Paracoccidioidomycosis develops as a chronic progressive disease and the lesions are related both to fungi and its antigens.

Sabouraudia, 1979 Jun, 17(2), 155 - 61
{Study of yeast phase Histoplasma capsulatum antigens used for skin tests}; Negroni R et al.; The results of skin tests with two antigens of the yeast phase of Histoplasma capsulatum are presented . Both antigens were able to fix complement and form precipitating bands in the presence of sera from patients with active histoplasmosis . Their sensitivity was lower than the metabolic antigen usually employed in serology . Results of skin tests obtained with both yeast phase antigens and a standard histoplasmin coincided in animals infected with H . capsulatum . Only one cross reaction was observed in animals inoculated with Paracoccidioides brasiliensis . Skin tests in humans were conducted on patients with and without mycotic disease . The percentages of positive reactions in patients with histoplasmosis were not significantly different between control histoplasmin and whole cell extracts . In the patients with non mycotic diseases the frequency of positive tests varied between 28.8% and 32%, which agrees with previous statistical data for the general population of the area . Equally the positive percentage of 55% and 68% in patients with paracoccidioidomycosis coincided with the results of previous studies . The histological patterns of these skin tests showed that they were produced by cell mediated hypersensitivity . The sensitivity of a whole yeast cell extract was similar to histoplasmin L48, but its preparation was quicker and easier to perform and it had no foreign substances from the culture medium, so we think that it would be easier to standardize it chemically.

Sabouraudia, 1979 Jun, 17(2), 139 - 44
Paracoccidioidal infection in the wife of a patient with paracoccidioidomycosis; Conti-Diaz IA et al.; Three agar immunoprecipitin techniques (double immunodiffusion, immunoelectrophoresis and immunoelectroosmophoresis-immunodiffusion) made with paracoccidioidin and serum of a paracoccidioidomycosis patient's wife, permitted us to observe a specific band in 6 successive samples of blood taken from the wife over a period of 21 months . The case represents an example of a subclinical paracoccidioidomycosis infection that is usually diagnosed in its disseminated, progressive form . Three possible sources of infection are discussed . But an interhuman contagion appears to be the most feasible.

Schweiz Med Wochenschr, 1979 May 5, 109(18), 693 - 9
{South American blastomycosis (paracoccidioidomycosis) in Switzerland . Clinical course and morphological findings in a case following long-term therapy}; Stanisic M et al.; The clinical course and morphological findings are reported of visceral paracoccidioidomycosis or South American blastomycosis with lung involvement in a 47-year-old male after specific antimycotic treatment for 11 years . The patient had been infected during a stay in Sao Paulo, Brazil, from 1950 to 1954 . The diagnosis was established in 1959 after his return to St . Gall, Switzerland, in tissue from buccal mucosa and cervical lymph node biopsy and in fungus cultures . The patient was treated with Fungizone (amphotericin B) and with the sulfonamide Fanasil . He died in 1970 from acute right heart failure . Autopsy revealed multiple encapsulated mycotic foci in both lungs, together with healed foci and pulmonary fibrosis . Histological examination showed a large amount of Paracoccidioides brasiliensis in the mycotic foci, but cultural proof was no longer possible . In the buccal mucosa and lymph nodes, only fungus-free scars were observed . There are only a few effective antimycotic agents . With a thorough knowledge of their side effects and dosage modalities, it is possible to achieve highly satisfactory results.

Proc R Soc Lond B Biol Sci, 1979 Apr 11, 204(1155), 165 - 87
From extracellular to intracellular: the establishment of mitochondria and chloroplasts; Whatley JM et al.; Paracoccus and Rhodopseudomonas are unusual among bacteria in having a majority of the biochemical features of mitochondria; blue-green algae have many of the features of chloroplasts . The theory of serial endosymbiosis proposes that a primitive eukaryote successively took up bacteria and blue-green algae to yield mitochondria and chloroplasts respectively . Possible characteristics of transitional forms are indicated both by the primitive amoeba, Pelomyxa, which lacks mitochondria but contains a permanent population of endosymbiotic bacteria, and by several anomalous eukaryotic algae, e.g . Cyanophora, which contain cyanelles instead of chloroplasts . Blue-green algae appear to be obvious precursors of red algal chloroplasts but the ancestry of other chloroplasts is less certain, though the epizoic symbiont, Prochloron, may resemble the ancestral green algal chloroplast . We speculate that the chloroplasts of the remaining algae may have been a eukaryotic origin . The evolution or organelles from endosymbiotic precursors would involve their integration with the host cell biochemically, structurally and numerically.

Antonie Van Leeuwenhoek, 1979, 45(2), 265 - 74
Beta-1-3-glucanase and dimorphism in Paracoccidioides brasiliensis; Flores-Carreon A et al.; Mycelial and yeast forms of P . brasiliensis were tested for several glucohydrolases . In addition to high levels of beta-glucanases, low amounts of alpha-glucanase, chitinase and maltase were found . Tests for invertase, amylase and lactase were negative . The levels of beta-1,3-glucanase were higher in the mycelial form . The shift to the mycelial phase correlated with an increase in the levels of beta-1,3-glucanase . The enzyme was present in the cytoplasm, cell wall and culture medium . The extracellular enzyme was purified 42 fold by ammonium sulphate precipitation and gel filtration . Maximal activity was obtained at 60 degrees C and pH of 5.0 (acetate buffer or pH 6.0 (phosphate buffer) . Its Km was 0.205 mg/ml . The cell wall-bound enzyme showed a higher temperature optimum . Optimum pH and Km were also slightly different . Following treatment of the cell walls with chitinase, beta-1,3-glucanase was released into the medium.

Sabouraudia, 1978 Dec, 16(4), 279 - 84
Histoplasma capsulatum: chemical variability of the yeast cell wall; San-Blas G et al.; Four strains of Histoplasma capsulatum were analyzed to observe any variations in their cell wall composition . Strain G-184B produced the same amount of sugars reported by Domer (2) although qualitative analyses agreed with Kanetsuna's report (4) as far as the presence of glucose, galactose, and mannose was concerned . Our results agree with previous reports in classifying H . capsulatum into chemotypes I and II, the latter having more alpha-glucan in its cell wall . A decrease in the amount of fraction 2 (alpha-glucan) of strain G-184B was observed when the strain was subcultured in vitro for many years, an effect similar to that reported for Paracoccidioides brasiliensis (12, 13).

J Neurosurg, 1978 Sep, 49(3), 429 - 33
Paracoccidioidomycosis of the skull . Case report; Krivoy S et al.; A case of paracoccidioidomycosis of the skull is presented . No evidence of a previous lung, mucous membrane, or nervous system infection was found . Radiological and surgical findings suggested osteomyelitis . The authors stress the importance of including paracoccidioidomycosis in the differential diagnosis of osteolytic skull lesions in countries where this fungus is endemic.

J Neurosurg, 1978 Sep, 49(3), 425 - 8
South American blastomycosis presenting as a posterior fossa tumor . Case report; Araujo JC et al.; An unusual case of infection of the central nervous system by Paracoccidioides braziliensis, presenting as posterior fossa tumor, is discussed and the pertinent literature reviewed.

Mycopathologia, 1978 Aug 10, 63(3), 161 - 5
{Comparative study of immunoelectrophoresis (IEF) and immunoelectroosmophoresis-immunodiffusion (IEOF-ID) used in the diagnosis of paracoccidioidomycosis}; Conti-Diaz IA et al.; Immunoelectroporesis (IEF) and immunoelectroosmophoresis-immunodiffusion (IEOP-ID) (1) were comparatively used in the diagnosis of 16 patients with mycologically proved paracocidioidomycosis . In IEF, 5 different precipitin arcs were found and identified with arabic numbers . Arc . '1', cathodic, present in all the patients, is assimilated to specific arcs previously described by other authors . In IEOP-ID both 'cathodic' and 'anodic' arcs were observed in all the sera . A high number of precipitin arcs were revealed by IEOP-ID technique in comparison to IEF in every case . This should be due to the presence of cathodic arcs 'I' and '2' of the immunoelectrophoregram at both sides of the IEOP-ID preparate.

Br J Exp Pathol, 1978 Aug, 59(4), 339 - 44
Experimental paracoccidioidomycosis: cranial and nasal localization in mice; Hay RJ et al.; An experimental mouse model for paracoccidioidomycosis (South American blastomycosis) is described . When distribution of cranial lesions following i.v . injection was investigated, invasion of the nasal mucosa with subsequent discharge of budding Paracoccidioides brasiliensis cells into the nasal cavity was noted . The possible significance of this finding in terms of the processes associated with naturally occurring paracoccidioidomycosis is discussed.

J Oral Surg, 1978 Aug, 36(8), 625 - 30
Disseminated South American blastomycosis (paracoccidioidomycosis): report of case; Limongelli WA et al.; The 11th case of South American blastomycosis occurring in the United States has been reported . Therapy with amphotericin B and sulfisoxazole has been discussed.

Am J Trop Med Hyg, 1978 Jul, 27(4), 808 - 14
Paracoccidioidin and histoplasmin sensitivity in Coari (state of Amazonas), Brazil; Mok WY et al.; A skin test survey with paracoccidioidin and histoplasmin was conducted on 495 residents of Coari in the Brazilian state of Amazonas . Positive dermal reactions to paracoccidioidin and histoplasmin were seen, respectively, in 13.9% and 50.1% of the study subjects . Specific reaction to paracoccidioidin was observed in 1.6% of the individuals, and to histoplasmin in 37.8% . Cross-reactivity between the two antigens in persons who reacted positively to both skin tests was not totally reciprocal . There were no significant differences in dermal reactivity to either of the two antigens in either sex, or among different occupational groups . No precipitating antibody to paracoccidioidin or histoplasmin was detected in the sera of the skin test-positive individuals by the immunodiffusion test . Skin test positivity in the general population of Coari reaffirmed the concept of benign, self-limited infection in paracoccidioidomycosis and histoplasmosis . It also identified the equatorial forests of the Upper Amazon Basin as endemic zones of these two mycoses.

Am J Trop Med Hyg, 1978 Jul, 27(4), 801 - 7
Paracoccidioidomycosis (South American blastomycosis): treatment with miconazole; Stevens DA et al.; Six patients with multisystem paracoccidioidomycosis proven by serology and culture or smear were treated with relatively brief courses of intravenous miconazole . Two had relapsed following prior therapy; 6 had active pulmonary, 4 laryngeal, 2 oropharyngeal, 2 lymphoid, and 1 abdominal disease . Paracoccidioides brasiliensis was highly susceptible to miconazole in vitro; minimal inhibitory concentration was less than or equal to 0.001 microgram/ml . Clinical examination showed a prompt and objective response in all patients, confirmed by smear or culture and X-rays; in 4/6 serological response was shown . Side effects were minor . Two patients relapsed 3--5 mo after therapy; another had a rise in antibody 6 mo after therapy and was given maintenance oral sulfa . One remains in remission 7 mo after treatment; two given oral sulfa after response to miconazole remain in remission 4--6 mo after treatment . Paracoccidioidomycosis responds well to miconazole, but longer courses may be needed to prevent relapse.

Sabouraudia, 1978 Jun, 16(2), 151 - 63
Immune responses in paracoccidioidomycosis . A controlled study of 16 patients before and after treatment; Restrepo A et al.; Serum electrophoresis patterns and various measures of specific and non-specific immune competence were determined in 16 patients with paracoccidioidomycosis, at time of diagnosis and 6 months after therapy . The results were compared with those furnished by the study of 16 control subjects, matched by age and sex . Once treated, the patients approached normality in some parameters . Untreated patients had significantly diminished albumin levels with increased alpha 1, alpha 2 and gamma fractions . Immune gamma globulin G (IgG) was elevated and remained so during therapy . Both before and after treatment patients had diminished total numbers and decreased percentages of E rosettes; they also had depressed lymphocyte transformation with phytohemagglutinin (PHA) and paracoccidioidin (P) . Also, untreated patients exhibited the lowest skin test responses to PHA, purified protein derivative (PPD), P and candidin (C); significant differences, however, were limited to the former 2 antigens . All untreated patients had detectable antibody titers against P . brasiliensis; these titers had a tendency to drop during treatment . No direct correlation was found between elevated serum fractions, presence of antibodies and depressed cellular immunity.

Sabouraudia, 1978 Jun, 16(2), 103 - 13
Bovine experimental paracoccidioidomycosis intradermic test standardization; Da Costa EO et al.; Three intratesticulary inoculated bovines revealed to be susceptible to experimental paracoccidioidomycosis . The experimental infection was self limited with no tendency to dissemination during a follow up period of five months . The histopathologic lesions characterized by granulomatous inflammatory foci, associated or not to necrosis, were found in the testicles, spermatic cords and testicular tunicae . In some of both lesions types the yeast cells of P . brasiliensis were present . The experimental infection did not cure in a follow up period of five months . The immunological response either cellular or humoral were delayed in relation to what happens in other animal species . The three experimentally infected bovines were utilized for some standardization of the paracoccidioidin intradermic test . A type and dose of an antigen which gives a clear reading for the positive tests was determined . The humoral responses were detected mainly by the complement fixation reaction . It was not possible to demonstrate humoral antibodies by the agar immunodiffusion test.

Rev Asoc Argent Microbiol, 1978 May-Aug, 10(2), 61 - 4
{Immunodiffusion tests in gel media with the addition of polyethyleneglycol 6000 for the serodiagnosis of mycoses}; Zaror L et al.; Different immunodiffusion techniques with and without the addition of polyetilenglycol 6000 (PEG), were studied to determine its effect on the sensitivity of these reactions . One hundred thirteen sera from patients who suffered or had suffered deep mycoses (paracoccidioidomycosis: 49, histoplasmosis: 25, aspergillosis: 25, candidiasis: 8 and coccidioidomycosis: 6) were examined by the quantitative Ouchterlony's immunodiffusion procedure . Regular medium and media with 2% and 4% PEG were used . Eighty two out of the one hundred thirteen sera were positive for the regular medium and 91 for the medium containing 2% of PEG; furthermore, an increase of 1 or 2 two fold dilutions in the titers was observed in 40% of the sera, for the later media . Twenty one sera from aspergillosis cases were examined by agarose gel immunoelectrophoresis, 80% had more precipitin bands in the medium with 2% of PEG . Thirty four serum samples of patients suffering aspergillosis, paracoccidioidomycosis and histoplasmosis were studied using the agarose electroosmophoresis with the secondary immunodiffusion test . An increase in the number of the anodic bands were observed in 55% while 64% presented more catodic bands, when the PEG medium was used . This results would indicate that the addition of 2% PEG 6000 to the regular medium improves the sensitivity of the immunodiffusion tests for mycoses.

Mycopathologia, 1978 Apr 14, 63(1), 53 - 6
Progressive pulmonary paracoccidioidomycosis a study of 34 cases observed in Rio Grande do Sul (Brazil); Londero AT et al.; Data on 34 patients with progressive pulmonary paracoccidioi domycosis seen in the State of Rio Grande do Sul (Brazil) are reviewed . Clinical manifestations were similar to those of a prolonged or a recurrent undifferentiated respiratory infection . Roentgenographic findings were also non-characteristic . A mycologic diagnosis was readily made when sputum was available.

Sabouraudia, 1978 Mar, 16(1), 55 - 62
Specific double diffusion microtechnique for the diagnosis of aspergillosis and paracoccidioidomycosis using monospecific antisera; Yarzabal LA et al.; Using experimental reference sera against species-specific antigens of Aspergillus fumigatus and Paracoccidioides brasiliensis in a microdouble diffusion technique, a simple and specific test for the immunodiagnosis of aspergillosis and paracoccidioidomycosis has been developed . Only sera that produced lines of identity with either one of the bands formed by the anti-C2 or the anti-E2 reference sera were considered positive for aspergillosis or paracoccidioidomycosis, respectively . The sensitivity of the diagnostic test was similar to those of the classical double diffusion and the immunoelectrophoresis test . No false positives were found in sera obtained from patients affected by other mycoses, nor from healthy controls . The amount of reagents for the specific test was ten fold less than that required by the classical double diffusion test.

Folia Microbiol (Praha), 1978, 23(3), 198 - 201
Effects of cyanein and ramihyphin A on the dimorphism of Paracoccidioides brasiliensis; San-Blas G et al.; As a preliminary step in the study of dimorphism in Paracoccidioides brasiliensis, the effects of cyanein and ramihyphin A were studied . These antibiotics have been reported to induce morphological changes in fungi . The results obtained suggest that ramihyphin A induce swelling of hyphae while partially inhibiting Y leads to M transformation with the production of an incipient and swollen mycelium . Cyanein did not affect the mycelial morphology as did ramihyphin A . However, the Y leads to M transformation was inhibited and, also, the M leads to Y transformation was blocked with the production of a few yeast cells which were not released from the mycelium.

Hautarzt, 1978 Jan, 29(1), 17 - 21
{Tropic-subtropic fungus infections in Germany}; Krempl-Lamprecht L; Observations by the author and other workers on exotic mycoses in Germany are used in order to establish several groups of patients . The following mycoses from tropical and subtropical areas and their causative agents are mentioned: Tinea nigra (Cladosporium werneckii), south American blastomycosis (Paracoccidioides brasiliensis), coccidioidomycosis (Coccidioides immitis), histoplasmosis (Histoplasma capsulatum), mycetoma (Madurella mycetomi), dermatophytosis/tinea capitis (Trichophyton soudanense, Trichophyton violaceum, Microsporum ferrugineum), sporotrichosis (Sporothrix schenckii), chromomycosis (Fonsecaea pedrosoi).

Mycopathologia, 1977 Dec 16, 62(2), 77 - 86
Paracoccidioides brasiliensis: cell wall structure and virulence . A review; San-Blas G et al.; Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis or South American blastomycosis . Many aspects of the disease and its agent are unknown . One of the most important factors regarding the infection and the host-parasite relationships seems to be the fungal cell wall whose biochemical aspects are reviewed here . Biochemical studies, done mainly by Kanetsuna et al., (21,22), have demonstrated that the yeastlike (Y) and the mycelial (M) forms have chitin as a common polysaccharide, with alpha-1, 3-glucan in the Y form and beta-1, 3-glucan in the M form . These polysaccharides are fibrillar and determine to some degree the fungal shape . Moreover, an amorphous galactomannan is found in the cell wall of the M form . This compound is responsible for the antigenic properties of the cell wall (1) . Recent studies (30-33) suggest that the cell wall does not possess a stable chemical structure but a rather changing one, as a function of the environment in which the fungus is grown . At the same time, the cell wall composition seems to correlate with the degree of virulence of the particular strain . From these observations it may be deduced that the constituent polysaccharides of P . brasiliensis cell wall, play an important role in the active protection of the fungus against the defensive mechanisms of the host.

Sabouraudia, 1977 Nov, 15(3), 297 - 303
Cell wall analysis of an adenine-requiring mutant of the yeast-like form of Paracoccidioides brasiliensis strain IVIC Pb9; San-Blas G et al.; An adenine-requiring mutant of Paracoccidioides brasiliensis strain IVIC Pb9 was isolated after treatment of the yeast-like (Y) form with nitrosoguanidine . Cell wall analysis of this mutant (strain IVIC Pb141) showed an increase in the amount of alpha-1,3-glucan and a virtual disappearance of the antigenic galactomannan . At the same time, a higher degree of virulence was observed for the mutant . These results agree with the hypothesis presented before (16) about a relationship between cell wall polysaccharides and pathogenicity in P . brasiliensis.

Chest, 1977 Jul, 72(1), 100 - 2
Paracoccidioidomycosis (South American Blastomycosis) in the United States; Bouza E et al.; The findings in a patient with paracoccidiodomycosis (South American blastomycosis) diagnosed by open-lung biopsy and treated successfully with a combination of trimethoprim and sulfamethoxazole are reported, and the clinical spectrum of the disease is reviewed . Although paracoccidioidomycosis is rarely encountered in the United States and is clinicially similar to other deep mycoses, it should be considered in patients who are suspected of having a fungal infection and have had previous exposure in an area endemic for paracoccidiodomycosis.

Vet Pathol, 1977 Jul, 14(4), 368 - 71
Paracoccidioidomycosis (South American blastomycosis) in a squirrel monkey (Saimiri sciureus); Johnson WD et al.; A female squirrel monkey (Saimiri sciureus) had granulomatous lesions in the liver and colon . There were many fungal organisms in sections of liver and many of these organisms had multiple buds on their surface . Although we did not prepare fungal cultures, the appearance of the organisms was sufficient to identify them as Paracoccidiodes brasiliensis, the cause of paracoccidioidomycosis (South American blastomycosis).

Z Exp Chir, 1977 Apr, 10(2), 96 - 101
{Experimental studies on the domestic pig about reconstruction of the injured organ of continence}; Anke H et al.; In 12 domestic pigs, body weight ranging between 30 and 40 kg at operation, under general anesthesia the continence organ was paracoccygeally dissected on one side, and in 6 other animals bilaterally, and immediately thereafter reconstructed . The reconstruction was done paying regard to the fascial skeleton . In all cases the wounds healed primarily . The functional results were good, incontinence was not observed.

Clin Exp Immunol, 1977 Apr, 28(1), 89 - 98
Cell-mediated immune responses in patients with paracoccidioidomycosis; Mok PW et al.; We tested the hypothesis that symptomatic infection with Paracoccidioides brasiliensis caused impaired host cellular immune responses . In a cross-sectional study in Colombia, the immune responses of thirty-six patients with paracoccidioidomycosis were compared with those of sixty normal individuals . Patients demonstrated increased skin sensitivity to paracoccidioidin (para) and histoplasmin, and reduced reactivity to candidin and dinitrochlorobenzene as compared to controls . The skin test response to tuberculin (PPD) was similar to that of controls . In vitro lymphocyte transformation (LT) and leucocyte migration responses to phytohaemagglutinin and PPD did not differ in patients and controls; these responses to PPD correlated with skin sensitivity in controls, but not in patients . LT and inhibition of leucocyte migration to para were seen in more patients than controls; the latter response correlated with skin sensitivity in controls only . Positive LT to para was associated with absence of antibodies to P . brasiliensis . Analysis of symptomatic patients suggests that the prevalence of para skin test positivity was lowest in patients with the longest duration of disease; this implies decrease in specific cell-mediated immunity with prolonged active infection . Analysis of clinically cured patients suggests that the prevalence of para skin sensitivity and LT to para and PPD increased with time elapsed since diagnosis; this implies development or restoration of immunocompetence upon clinical recovery . Results of a preliminary longitudinal study on the immunological responses of six patients with active paracoccidioidomycosis are compatible with the above observations.

Br J Exp Pathol, 1977 Apr, 58(2), 209 - 14
X-ray microanalysis as applied to fungal tissues; Thibaut M et al.; Analytical electron microscopy combines the techniques of high-resolution electron microscopy and high-sensitivity X-ray microanalysis of samples . Spectrometry of the elements (characteristic X-rays produced by a scanning electron microprobe) was employed to detect some elements of Mendeleev's classification in pathogenic fungi for humans . X-ray microanalysis applied in wavelength dispersive spectrometry was used to study Coccidioides immitis, Paracoccidioides brasiliensis and Trichosporum cutaneum.

Infect Immun, 1977 Mar, 15(3), 897 - 902
Induction of the synthesis of cell wall alpha-1,3-glucan in the yeastlike form of Paracoccidioides brasiliensis strain IVIC Pb9 by fetal calf serum; San-Blas G et al.; In vitro subculturing of the yeastlike form of Paracoccidioides brasiliensis strain IVIC Pb9 leads to the disappearance of alpha-1,3-glucan as a main component of its cell wall . However, the addition of fetal calf serum to the growth medium induces the synthesis of this polysaccharide . It is suggested that the synthesis of alpha-1,3-glucan in the cell wall of the yeastlike form of P . brasiliensis is induced by external factors.

Sabouraudia, 1977 Mar, 15(1), 79 - 85
Identification and purification of the specific antigen of Paracoccidioides brasiliensis responsible for immunoelectrophoretic band E; Yarzabal LA et al.; A new purified antigen (E2) of Paracoccidioides brasiliensis mycelial growth phase was isolated by immunoadsorption from a crude metabolic soluble extract of the fungus . The antiserum prepared in a rabbit by inoculation of E2 antigen developed only one immunodiffusion line with the crude metabolic extract . Findings on immunological analysis showed that E2 antigen is the antigenic component of immunoelectrophoretic band E . The isolated antigens did not possess detectable alkaline phosphatase activity . It reacted in immunodiffusion tests with all the sera (14/14) from P . brasiliensis infected patients containing precipitating antibodies.

Infect Immun, 1977 Feb, 15(2), 343 - 6
Host-parasite relationships in the yeastlike form of Paracoccidioides brasiliensis strain IVIC Pb9; San-Blas G et al.; The yeastlike form of Paracoccidioides brasiliensis strain IVIC Pb9 reduced the amount of alpha-1,3-glucan in its cell wall from 45 to 3% when subcultured in vitro for several years . This strain regained its alpha-1,3-glucan up to 25% of the total cell wall when grown in vivo . A mutant strain of P . brasiliensis Pb9, named IVIC Pb140, reported to have 1,3-mannan instead of alpha-glucan in the cell wall, could not be recovered from experimentally infected animals . The existence of some relationship between the presence of alpha-1,3-glucan in the cell wall of the yeastlike form and the pathogenicity of this fungus is suggested in this report.

J Bacteriol, 1977 Jan, 129(1), 138 - 44
Isolation and preliminary characterization of auxotrophic and morphological mutants of the yeastlike form of Paracoccidioides brasiliensis; San Blas F et al.; N-methyl-N'-nitro-N-nitrosoguanidine, which is known to be a very effective mutagen in many systems, was used to induce mutants in the yeastlike form of Paracoccidioides brasiliensis strain IVIC Pb9, an imperfect fungus . Forty-three auxotrophic and 27 prototrophic morphological mutants were isolated after treatment with 50 mug of nitrosoguanidine per ml in 0.1 M citrate buffer, pH 5.0 . Auxotrophic mutants required primarily either amino acids, purines, or pyrimidines . Some auxotrophs were also morphological mutants . The main morphological difference from the parental strain was the texture or the color of the yeast-like colonies . Only one prototrophic morphological mutant differed in the size and form of the yeastlike cells when compared with the parental strain . Suxotrophic mutants were used in pairwise combination to attempt heterokaryon formation without success.

Proc R Soc Med, 1977, 70 Suppl 1, 35 - 9
Treatment of South American blastomycosis (paracoccidioidomycosis) with miconazole by the oral route: an on-going study; Lima NS et al.; Results are presented from 12 patients of both sexes, whose ages range from 34 to 65 years, observed over a period of 16 months and receiving miconazole treatment for South-American blastomycosis . Ten of them were being treated for the first time and the remaining 2 presented relapses after treatment with other chemotherapeutic agents . The blastomycotic lesions were localized in skin, mucosa, lung and lymphatics . The drug was administered orally, at a dosage of 1 g three times daily . One relapsing patient had his first daily oral dose replaced by an intravenous dose of 200 mg of miconazole diluted in 250 ml of glucose solution during the initial four weeks . The criterion for diagnosis was finding of the fungus in sputum and/or in the material collected through scrapings or biopsy of the lesions . All patients were treated in hospital until the cure was apparent, clinical examinations being conducted weekly and bi-weekly . Bi-weekly laboratory examinations were performed to evaluate the patient's tolerance to the drug . All treated patients presented complete healing of cutaneomucous lesions (mean time: 4 weeks) and involution of lymphatic and pulmonary features (mean time: 4 months) . Two of them still presented palpable lymphatics after 5 months of treatment, in spite of the cure of mucosal and pulmonary lesions . Monitoring the progress of the cured patients was and is being carried out quarterly . Currently, this observation period ranges from three to 15 months . Nine patients are still returning and none have shown the reappearance of mycotic lesions . Diarrhoea was the only side-effect observed after a period of therapy, but it was easily controlled by specific medication (kaolin, pectin, &c.) . In a single case the treatment was interrupted because of this symptom.(ABSTRACT TRUNCATED AT 250 WORDS)

Proc R Soc Med, 1977, 70 Suppl 1, 24 - 8
Results of miconazole therapy in twenty-eight patients with paracoccidioidomycosis (South American blastomycosis); Negroni R et al.; Results are presented of treatment with miconazole, orally and intravenously, in patients with paracoccidioidomycosis . Twenty-eight male patients aged from 34 to 66 years and exhibiting various clinical forms of the disease were studied . Twenty-five came from endemic areas in north east Argentina (Chaco, Formosa, Misiones, Corrientes and northern Santa Fe) and the remaining three from Paraguay . Twenty patients were engaged in agricultural work or at woodmills . single or multiple lesions were observed in 24 cases . Thirteen were suffering from infection of the larynx and in two of them a tracheotomy was necessary . Twenty-three showed pulmonary lesions on X-rays . Twelve had ganglionic lesions, eight had cutaneous lesions and one patient had osteoarthritis of the knee . One patient had hepatomegaly which was unrelated to chronic alcoholism . Fourteen patients had received previous treatments such as sulphonamides and amphotericin B (7 cases); sulphonamides (3), sulphonamides and the combination sulfamethoxazole + trimethoprim (3), and one patient had received all three medications . All patients had relapsed before starting miconazole therapy . Diagnosis was established by the presence of P . brasiliensis in all cases, recovered either from cutaneous or mucosal biopsy samples or from the sputum . Complement fixation tests were positive in all patients at the onset of the treatment and the immunodiffusion reactions showed precipitation bands in 27/28 patients . Skin tests with P . brasiliensis antigens proved to be positive in 18 cases and negative in 10 . The erythrocyte sedimentation rate was markedly accelerated in 22 patients (greater than 20 mm in the first hour).(ABSTRACT TRUNCATED AT 250 WORDS)

Sabouraudia, 1976 Nov, 14(3), 299 - 34
{Experimental paracoccidioidomycosis in the mice induced intransally}; Moreno AR et al.; A study was undertaken to determine the possibility of inducing paracoccidioidomycosis in mice exposed to the mycelial phase of P . brasiliensis . Two strains of the fungus, designated FG and LA, were grown separately in media favoring the production of spores by the mycelial phase . These were collected and used for nasal instillation of 328 cortisone treated-mice . Animals were observed for a period of 16 weeks and sacrificed periodically . Pulmonary infection was obtained in 38.1% of the animals, with dissemination to spleen and liver occurring in 14.3% of the cases . The infection was not lethal . One of the strains (LA) proved to be move virulent than the other inducing a more severe type of pulmonary infection . The result of the study indicate that the mycelial phase of P . brasiliensis can give rise, by the inhalatory route, to active murine infections.

Sabouraudia, 1976 Nov, 14(3), 275 - 80
Isolation of a specific antigen with alkaline phosphatase activity from soluble extracts of Paracoccidioides brasiliensis; Yarzabal LA et al.; A specific antigen of Paracoccidioides brasiliensis was isolated from a metabolic extract of the fungus . The extraction was made by specific adsorption to and subsequent elution from a column containing a cross linked polymer to which the antibodies of a monospecific rabbit serum had been covalently attached . The purity of the final product was demonstrated by immunodiffusion analysis of the eluate using immune serum produced in a sensitized rabbit . The purified antigen was shown to have cationic electrophoretic mobility and alkaline phosphatase activity.

Sabouraudia, 1976 Nov, 14(3), 265 - 73
{Preparation and study of a Paracoccidioides antigen needed for skin tests}; Negroni R et al.; A cellular antigen from Paracoccidioides brasiliensis, obtained from the supernate of the disrupted yeast phase, was studied . It was prepared by a method similar to that for obtaining the spherulin from Coccidioides immitis . This antigen is composed of 55 mug/mg of polysaccharides, determined by the phenol method, and 7-8 mug/mg of protein, determined by Folin-Ciocalteu's technique . In vitro tests of antigenicity were done by immunodiffusion and complement fixation . The optimum dilution of the antigen was 0-5 mg/ml determined by microtiter complement fixation . The in vivo standardization of the cellular paracoccidioidin was performed on three groups of patients . The first was composed of 56 patients with mycologically proved paracoccidioidomycosis . The disease was active in 32 and clinically healed in 24 of this group . The second was composed of 15 cases of histoplasmosis with strong histoplasmin skin tests . The third group were 70 patients with no mycotic pulmonary diseases who had come from different zones in Argentina . Each individual was injected with 0-1 ml cellular paracoccidioidin (3 mg/ml), 0-1 ml of Fava Netto's antigen diluted 1/10, and 0-1 ml histoplasmin L48, diluted 1/100 . The cellular paracoccidioidin skin test was positive in 44/56 (78.5%) patients with paracoccidioidomycosis . The Fava Netto's antigen gave 42 (75%) positive results and the histoplasmin skin tests gave 28 (50%) in the same group . Twenty-eight (50%) presented positive histoplasmin skin tests . The paracoccidioidin skin test was positive in 2 of the histoplasmosis group (13-3%) and the Fava Netto's antigen gave 3 positive results in the same group (20%) . The histoplasmin skin test was positive in 32% of the individuals with no mycotic disease . Ten per cent of these exhibited positive reaction with both P . brasiliensis antigens . Of those paracoccidioidomycosis cases (Group 1) who had negative skin tests with 3 mg/ml of the cellular paracoccidioidin 7/10 gave positive skin tests when tested at a concentration of 8 mg/ml . Characteristic changes of cell medicated hypersensitivity were observed in the histopathological studies of the cellular paracoccidioidin skin test.

Mycopathologia, 1976 Oct 22, 59(3), 163 - 9
Determination of the growth curves of the mycelial and yeast forms of Paracoccidiodes brasiliensis; Arango M et al.; The growth curves of 2 different strains of P . brasiliensis were determined . Cultures were made in a dialyzed trypticase soy broth and the growth assesed at selected intervals by means of viable cell counts . In the yeast form, both strains exhibited un uniform pattern of growth; the mycelial forms were also similar although one of the strains survived for a longer period of time . When the 2 yeast curves were compared with the mycelial ones, large differences were noticed . Thus, the mean survival time for the yeasts was 13.5 days while it was 50.25 days for the mycelia . During the exponential phase, the mean rate of growth was accelerated for the yeasts (0.110) in comparison with the one exhibited by the mycelia (0.0265) . Irrespective of the form of growth and for both strains, death occurred abruptly, a few hours after a period when colony counts were high, indicating that the fugus was viable at the preceeding interval.

Mycopathologia, 1976 Sep 24, 59(2), 67 - 80
{Paracoccidioidomycosis: an epidemic in the Republic of Paraguay, the center of South America}; Rolon PA; The investigation done on the frequency or incidence of Paracoccidioidomycosis in the Republic of Paraguay, with the cases appeared and registered in the Institute of Pathology of Asuncion, presents an incidence rate of 0.46 per 100,000 in the total population; 0.52 per 100,000 in the population at risk . Considering the exposed masculine population the rate is 1.03 per 100,000 and for the feminine 0.02 per 100,000 . The age group most affected is within the 50-54 year range with 3.54 per 100,000, the highest rate of all the groups studied . These are the incidence in a strongly exposed population which is controlled and well known . The period of 10 years (1960/69) which has been chosen for this investigation, shows a frequency of the mixed type (lymphatic-visceral or lymphoma-type) which reaches 25% of the total, and a low frequency for the pulmonary form which reaches a mere 12.5% . The mucocutaneous lesion with the involvement of the regional lymph nodes is the dominating form . Considering three consecutive 5 year periods between 1960 to 1974, no cases with proved pulmonary involvement were found until 1964; from 1965 to 1969 the percentage of pulmonary lesions in all the cases considered was 23.0% and from 1970 to 1974 reached to 38.4% . However, mucocutaneous and the lymphatic-visceral or mixed forms do not show significant variations . The rats are small and represent the incidence of this mycosis . It is suggested that a failure of the immunologic system would be found in those affected by the disease and there would be a strong resistence in the majority of the population exposed or within the endemic area of the infection.

Am J Med, 1976 Jul, 61(1), 33 - 42
The gamut of paracoccidioidomycosis; Restrepo A et al.; Paracoccidioidomycosis is a systemic mycosis of importance in Latin America . Because of its polymorphic manifestations, it is not always suspected and patients are sometimes misdiagnosed . Case histories of patients with paracoccidioidomycosis are presented in order to illustrate its various manifestations, with emphasis on the primary pulmonary localization.

Mycopathologia, 1976 Jun 18, 58(2), 63 - 70
Pathogenesis of paracoccidioidomycosis: a model based on the study of 46 patients; Giraldo R et al.; Forty-six Paracoccidioidomycosis patients were studied with emphasis on lung pathology . It was found that the greatest clinical involvement of the reticuloendothelial system occurred in younger individuals . On the other hand, the frequency of tegumentary lesions was low in young patients and increased with age . Lung involvement was nearly always demonstrated when searched for and showed no relationship to the patient's age . In the young patients the disease was acute while in the older individuals its course was chronic . The findings from this study permitted formulation of a model for the pathogenesis of paracoccidioidomycosis in which the respiratory tract is accepted as the primary site of infection . Based on this model, a classification of the various forms of the entity is proposed.

Rev Asoc Argent Microbiol, 1976 May-Aug, 8(2), 68 - 73
{Study of serologic cross reactions between the antigens of Paracoccidioides brasiliensis and Histoplasma capsulatum}; Negroni R et al.; A comparative study of serologic cross-reactions between histoplasmosis and paracoccidioidomycosis was carried out using complement fixation (CF) and agar gel immunodiffusion (ID) tests . Sera from 77 patients with paracoccidioidomycosis, 38 with histoplasmosis and 50 healthy individuals were studied . The Pan American Health Organization microtiter CF test and the Hupper ID technique were employed . The antigens were prepared by the method of Ajello as modified by Negroni . Paracoccidioidin CF test was positive in all patients with paracoccidioidomycosis; 29 of these (37%) presented serologic cross-reaction with histoplasmin . Histoplasmin CF test was positive in all but one of the patients with histoplasmosis and only 4 of them (10%) showed cross-reaction with paracoccidioidin . Positive reactions with the ID test were registered in 74/77 cases of paracoccidiodomycosis, with only one case of cross-reaction (1,3%) . The result for the ID test was positive in all but one of the cases of histoplasmosis, with only one cross-reaction with paracoccidiodin (2,7%) . The ID test seemed to be much more specific although it could be less sensitive . It was also easier to perform and less expensive than the CF test . Nevertheless the authors urge that the CF test also be carried out whenever posible, since the information obtained is likely to be of more value in follow-up and control of patients.

J Gen Microbiol, 1976 Apr, 93(2), 209 - 18
A morphological mutant of Paracoccidioides brasiliensis strain IVIC Pb9 . Isolation and wall characterization; San-Blas F et al.; A morphological mutant of Paracoccidioides brasiliensis strain IVIC Pb9 was isolated after treatment of the yeast-like (Y) form with nitrosoguanidine . Colonies of the mutant grown at room temperature did not show the whitish cotton-like morphology typical of the mycelial form of the parental strain . Y-cells were much smaller than those produced by the parent and grew forming chains of different sizes . The main chemical difference in the wall of the Y-form was the replacement of the alpha-I,3-glucan, typical of the parental strain, by an amorphous I,3-mannan in the mutant.

Ann Anat Pathol (Paris), 1976 Jan-Feb, 21(1), 117 - 34
{Paracoccidiodomycosis (South American blastomycosis): general review and report of cases}; Cabrera A; The author presents and comments upon 19 cases of paracoccidiodomycosis (South American Blastomycosis) . He sums up the fundamental epidemiologic and parasitologic aspects of the disease . He points out the diversity of its anatomoclinical features, and underlines the role of the pathologic anatomy in the diagnosis of the disease which necessitates of course an immunologic study . Histology also allows the appreciate the effect of specific treatments and to emphasize the formidable sclerogenic tendency of the disease when the patient has not been long enough under treatment.

Med Cutan Ibero Lat Am, 1976, 4(3), 199 - 204
{Miconazole per os in tinea and deep mycosis}; Rodriguez H et al.; For the last 6 years we have been using Miconazole cream in the treatment of tinea and vaginal candidiasis . We think that it is at least as good as the best drugs for this purpose, but consider it difficult to decide about its superiority . Therefore we refrain from describing this part of our experience in detail . We have employed Miconazole "per os" at the daily doses of 24-28 mg./kg . in treating 3 cases of tinea corporis or cruris by "Trichophyton rubrum" . Symptoms ceased in 3 days; mycologic examination turned negative in 2 weeks; treatment ended in apparent cure in 3 weeks . We have employed Miconazole "per venam" and "per os" in the treatment of: mycetomata (2) by "Streptomyces somaliensis", without success; mycetoma by "Madurella grisea" (1), without success; chromomycosis by a 5-flucytosine resistant strain of "Cladosporium carrionii" (1), without success; paracoccidioidosis (5) with lesions in mouth and lungs, with good results; leishmaniasis by "Leishmania brasiliensis" (1), without success; mucocutaneous disseminated candidiasis (1), with very good results . Tolerance has been excellent: but pruritus appeared from the third week with 600 or more mg . "per venam", in several patients . Doses varied between 10 and 50 mg./kg./day . One patient, who suffered with candidiasis, is taking 50 to 30 mg./kg./day since more than a year ago and, being a child, he is feeling well and growing to be normal . We recommend employing Miconazole against systemic canidiasis, sulpharesistant paracoccidioidosis and assaying it further in tinea (at least, in griseofulvin-resistant cases).

Sabouraudia, 1975 Nov, 13(3), 280 - 4
Carboxylic activity of giant cells of human granuloma produced by Paracoccidioides brasiliensis; Campo-Aasen I; The carboxilic activity of giant cells of human granuloma produced by P . brasiliensis was studied . The enzymatic activity was revealed by reddish-brown, purple red, and indigo-blue cytoplasmic precipitate, using the substrates alpha-naphthyl-acetate, naphthol-AS acetate and 5-bromo-4-chloro-indoxyl acetate respectively . The giant cells were intensely positive in all cases studied . We believe this esterasic activity is related to the lytic, lisosomic activity of the macrophages and giant cells in response to the activity by the P . brasiliensis in tissue.

Mycopathologia, 1975 Jul 30, 56(1), 21 - 4
Paracoccidioidomycosis with palpebral and conjunctival involvement; Belfort R Jr et al.; A case of pulmonary and lymphatic paracoccidioidomycosis followed by conjunctivo-palpebral involvement is studied in Sao Paulo (Brazil) . The Brazilian literature is reviewed . The most frequent clinic forms of ocular lesions in natural infection are described . The small number of human cases observed is discussed . The severity and frequency of ocular lesions in experimental animals, intracardiacally inoculated with P . brasilensis cultures suggest haematogenic ocular dissemination of the fungus, which may occur in the septicemic stage of the human paracoccidioidomycosis.

Sabouraudia, 1975 Jul, 13(2), 132 - 41
Identification of yeast phase of pathogenic fungi by the specificity of their aminopeptidase(s); Lee KL et al.; Specificity of aminopeptidase(s) was fluorimetrically determined in the yeast phase of Histoplasma capsulatum, H . duboisii, H . farciminosum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Candida albicans and Crytococcus neoformans . After individually incubating each of 26 amino acid-beta-naphthylamides with each yeast, the amount of each amino acid-beta-naphthylamide hydrolyzed was determined by measuring the free naphythylamine . This resulted in a reproducible profile of the aminopeptidase(s) for each fungus when medium, growth time, size of inoculum and incubation period were standardized . This technique provided a rapid and specific means of identification and differentiation among these yeasts . Specific amino acids were identified from the profile of each yeast as those rapidly liberated by the aminopeptidase(s) of that yeast . These amino acids delineated the amino acid requirement for the normal growth of each yeast.

Ann Parasitol Hum Comp, 1975 Jul-Aug, 50(4), 507 - 13
{Reactivity of a purified antigen of Paracoccidioides brasiliensis with paracoccidioidomycosis and histoplasmosis sera}; Torres JM et al.; The immunoelectrophoretic reactivity of a "crude" and a "purified" antigens of Paracoccidiodes brasiliensis against the sera of confirmed cases of paracoccidioidomycosis and histoplasmosis was evaluated . The "crude" antigen revealed precipitating antibodies in both the homologous and the heterologous human sera; the number of precipitating systems being higher with the former . The "purified" antigen reacted only with the homologous sera . It is postulated that the use of such "purified" antigen may significantly reduce the non specificity of the serologic tests in the immunodiagnosis of paracoccidioidomycosis.

Am J Epidemiol, 1975 Jun, 101(6), 512 - 6
Spherulin and coccidioidin: cross-reactions in dermal sensitivity to histoplasmin and paracoccidioidin; Levine HB et al.; Until recently coccidioidin has been the only antigenic preparation available for detecting delayed dermal sensitivity induced by an experience with Coccidioides immitis . It is prepared from autolysates of the mycelial phase (saprophytic) of the fungus . A more sensitive reagent, spherulin, was developed in 1969 from the spherule phase (parasitic) of the organism . Use of spherulin showed that coccidioidin failed to detect approximately 30% of individuals specifically sensitive to C . immitis . However the potential of spherulin to detect cross-sensitivity induced by Histoplasma capsulatum was unknown . This information was considered to be germane because of the capacity of coccidioidin to detect a histoplasmal experience . Accordingly, both reagents as well as paracoccidioidin were compared simultaneously in 365 Columbian soldiers from areas endemic for histoplasmosis but not for coccidioidomycosis . At standard strength both preparations detected nonspecific responses in 0.8% to 3% of the histoplasmin negative and positive subgroups, respectively . At 10-times standard strength both preparations cross-detected histoplasmin sensitivity comparably; 5.1% to 7.1% of histoplasmin-positive subjects reacted with the coccidioidal antigens . No pattern of cross-reactivity was observed between paracoccidioidin sensitivity and sensitivity to the coccidioidal antigens.

Sabouraudia, 1975 Mar, 13 Pt 1, 10 - 21
{Effect of phagocytosis in vitro on Paracoccidioides brasiliensis}; Restrepo A et al.; Peripheral leukocytes from 17 patients with paracoccidioidomycosis were mixed with yeast cells from Paracoccidioides brasiliensis and Rhodotorula sp . to ascertain their phagocytic and lytic capacities . The role of circulating antibodies in the process was also investigated by the use of autologous serum . The phagocytic capacity of the leukocytes was found to be normal for both types of yeasts . However, in the presence of the patient's serum, the percentage of P . brasiliensis cells ingested was increased (P smaller than or equql to 0.02) . Furthermore, in 70-5% of the cases the lytic process was increased and more P . brasiliensis cells were killed when such a serum was employed (P smaller than or equal to 0.0013) . This increased effect was not recorded for Rhodotorula sp . cells, thus indicating specificity . The peripheral leukocytes from patients with paracoccidioidomycosis are not defective . However, the success of the phagocytic process is aided by the opsonic action of the specific antibodies in the patient's serum.

Sabouraudia, 1975 Mar, 13 Pt 1, 22 - 9
Growth curves of the yeast-like form of Paracocidioides bradiliensis; San-Blas F et al.; Growth curves of the yeast-like form of 4 strains of Paracoccidioides brasiliensis based on colony counts on GGY agar and on cell counts weree made . Mean generation times wer 17, 13 and 21 h . for 3 of the strains . The kinetics of growth for all strains showed that dead cells were present in approximately the same proportion as living cells in the initial inocula and their number increased through the exponential phase of growth at a similar rate as that of living cells . Viability counts made in 2-week old cultures of all strains were negative . It is suggested that during growth P . brasiliensis continuously diffuses a metabolite which is lethal to the fungus . Strains of Blastomyces dermatitidis and Histoplasma capsulatum were also sensitive to this lethal effects.

Int J Dermatol, 1975 Mar, 14(2), 117 - 25
Infection versus disease in South American blastomycosis; Furtado T; The mechanism of infection in South American blastomycosis is discussed, and the probability of a mild or asymptomatic form of the disease, regressing spontaneously with subsequent immunity, in persons living in endemic areas . Primary lesions in the oral mucosa or in the skin have not been convincingly shown to occur in paracoccidioidomycosis . Several reports of systemic involvement of many organs with no evidence of skin and mucosal lesions support the theory of pulmonary entry.

Bull Soc Pathol Exot Filiales, 1975 Jan-Feb, 68(1), 46 - 50
Morphological conversion of 13 strains of three dimorphic fungi in tap and stream water; Sheiban ZB; Various strains of Sporotrichum schenckii, Histoplasma capsulatum and Paracoccidioides brasiliensis show partial to complete (ca 70%) conversion to yeast when the mycelial culture is grown on Sabouraud's dextrose agar at 25degreesC and palced in tap or stream water at 37degreesC . Conversion (ca 70%) to mycelial phase occurs when the yeast culture is grown on brain heart infusion agar at 37degreesC and then placed in tap or stream water at 25degreesC . It was observed that, with the dimorphic organisms and strains tested, enriched medium is not necessary for partial conversion to either phase because it occurs in tap and stream water . The change in morphology is assumed to be principally due to temperauture change, as reported for Blastomyces dermatitidis and H . capsulatum by other workers.

Med Cutan Ibero Lat Am, 1975, 3(4), 289 - 92
{Paracoccidioidomycosis . Accidental inoculation "in anima nobile." Report of a case}; Castro RM et al.; Publication Types:

Case Reports

What Is Activated Sludge?, What is Food Microbiology?, What Is Molecular Microbiology?, What Is Botulism?, What Is Antibiotic?, a, Bacteria, s, Microbes, s, Microbe, o, Microorganism, o, Microorganisms, c, Bacillus subtilis, e, Bacteriophages, c, Antibiotics, o, Escherichia coli, c, Escherichia coli, i, Yeasts, e, Bacillus anthracis, e, Enterobacteriacea, e, Bacillus, a, Clostridia, a, Eubacterium, s, Bacillus, r, Campylobacter, s, Multidrug resistant, a, Escherichia coli, o, Microorganism, r, Anaerobe, r, Eubacter, e, Streptococci, c, S. cerevisiae, o, Bacteroides

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005