Int J Syst Bacteriol, 1994 Apr, 44(2), 209 - 13 Gene arrangement and sequence of the 5S rRNA in Filobasidiella neoformans (Cryptococcus neoformans) as a phylogenetic indicator; Kwon-Chung KJ et al.; We cloned the 5S rRNA gene and determined its organization in the four genes encoding rRNAs in a ribosomal DNA repeat unit of Filobasidiella neoformans, the teleomorph of Cryptococcus neoformans . The 5S rRNA gene contained 118 nucleotides and was located 1 kb upstream from the 18S rRNA gene within the 8.6-kb fragment of the ribosomal DNA repeat unit . The sequence of the 5S rRNA gene from F . neoformans was more similar to the sequence of the 5S rRNA gene from Tremella mesenterica than to the sequences of the 5S rRNA genes from Filobasidium species . The arrangement of the rRNA genes in F . neoformans closely resembles the arrangement of the rRNA genes in mushrooms such as Schizophyllum commune, Agaricus bisporus, and Coprinus cinereus in that the 5S rRNA-coding region not only is located within the repeat unit that encodes the other rRNAs but also is transcribed in the same direction as the other rRNA genes . This is the first description of the arrangement of rRNA genes in a species belonging to the Heterobasidiomycetes. Strahlenther Onkol, 1994 Apr, 170(4), 195 - 205 {Supportive therapy during radiochemotherapy--prevention and therapy of infections}; Plasswilm L et al.; BACKGROUND: In current radiooncology the consistent use of best supportive care during aggressive combined treatment protocols is indispensible . Presently the optimal management of fever in granulocytopenic patients is controversially discussed . MATERIAL AND METHODS: Based on own clinical experiences and a literature review we report about empiric antibiotic and antifungal therapy in febrile patients with granulocytopenia . Particular consideration is given to the new antifungal agent fluconazole (compared to amphotericin B) and the beta-lactamase inhibitor sulbactam . We also discuss the use of hematopoietic growth factors and selective gastrointestinal decontamination . RESULTS: In fever of unknown origin the use of a two drug antibiotic combination containing an ureidopenicillin (acyl-penicillin) and an aminoglycoside is recommended . After five days of persisting fever additional antimycotic therapy is initiated . Fluconazole shows a high response rate with only few side effects in the treatment of infections with candida albicans and cryptococcus neoformans . In the early empiric antifungal therapy it is more and more replacing amphotericin B . With encouraging results sulbactam can be combined with piperacillin or mezlocillin during radiochemotherapy . Concerning G-CSF there are no general recommendations allowed . We prefer a calculated prophylaxis for patients who receive a myelotoxic chemotherapy and have a high individual risk for severe neutropenia . During the second day of reverse isolation we start a selective decontamination of the digestive tract until white-blood-cell-count increases to more than 1000 to 1500 granulocytes/mm3 . CONCLUSION: The radiooncologist should be able to completely manage prevention and treatment of infectious diseases to provide an optimal use of all new options in combined modality treatment in radiooncology. South Med J, 1994 Apr, 87(4), 537 - 8 Disseminated cryptococcal disease complicating steroid therapy for Pneumocystis carinii pneumonia in a patient with AIDS; Bernstein B et al.; Recent studies have suggested that steroid therapy may reduce the morbidity and mortality of HIV-associated Pneumocystis carinii pneumonia (PCP) in a select population of patients . However, the risks of steroid therapy for this group have not been well defined . We describe the case of a patient admitted with severe PCP whose treatment included high-dose steroids . During his hospitalization, overwhelming cryptococcal disease developed, contributing to his death . We postulate that the rapidity of progression was due, in part, to the steroid therapy . We have also reviewed the literature . We recommend screening for cryptococcal infection before beginning steroid therapy. Histol Histopathol, 1994 Apr, 9(2), 305 - 8 Pathological findings in a cat with cryptococcosis and feline immunodeficiency virus infection; Ramos-Vara JA et al.; This report describes the gross, histopathological, immunocytochemical and electron microscopic findings in a cat with systemic cryptococcosis and feline immunodeficiency virus (FIV) infection . Lymphadenopathy and cloudiness of leptomeninges were the major gross findings . Numerous cryptococcal yeasts were found in lymph nodes, brain, and lung, and were less common in the kidney and the eye . The inflammatory reaction varied in intensity and cell type (mononuclear through granulomatous) depending on the organ involved . Yeasts were mainly within phagocytes as revealed by electron microscopy . Some inflammatory cells were immunocytochemically-stained with anti-CD3 antibodies. Nihon Kyobu Shikkan Gakkai Zasshi, 1994 Apr, 32(4), 339 - 43 {A case of primary pulmonary cryptococcosis with increased serum carcinoembryonic antigen}; Igarashi T et al.; A case of primary pulmonary cryptococcosis with increased serum carcinoembryonic antigen (CEA) (7.0 ng/ml) is presented . The diagnosis was made by transbronchial lung biopsy (TBLB) and no abnormality was found in either gastrointestinal tract or immunity . Immunohistochemical study of the lung specimen showed that CEA was present on the surfaces of alveoli . The level of CEA fell to 0.8 ng/ml after administration of an antimycotic agent (Fluconazole) with simultaneous improvement of the chest radiographic findings . This case indicates that increased serum CEA depends on pulmonary cryptococcosis . TBLB and administration of antimycotic agents, instead of surgical resection, are useful in the diagnosis and treatment of this disease. Nihon Kyobu Shikkan Gakkai Zasshi, 1994 Apr, 32(4), 334 - 8 {An autopsied case of pleuro-pulmonary cryptococcosis}; Suzuki K et al.; We report a case of pleuro-pulmonary cryptococcosis . An 86-year-old man was admitted to the hospital with dyspnea, a high fever and an oppressive sensation in the chest . Chest X-ray on admission revealed massive pleural effusions, interstitial shadows and consolidation with air bronchograms in both lung fields . The cause of pleural effusion was unknown . The patient died one month later . Autopsy revealed severe pleural cryptococcosis and organizing pneumonia with a small number of cryptococci but without granuloma . To our knowledge, there have been very few documented cases of pleuro-pulmonary cryptococcosis with such massive bilateral pleural effusions. Clin Nephrol, 1994 Apr, 41(4), 230 - 2 Cryptococcal peritonitis in peritoneal dialysis patients: a case report; Mansoor GA et al.; Peritonitis in patients on chronic peritoneal dialysis remains a major problem . Most commonly this is due to bacterial infection, but fungal peritonitis is also a treatment dilemma . Peritonitis due to Cryptococcus neoformans is an unusual event, with fewer than ten cases reported . This case report documents a case of cryptococcal peritonitis in a diabetic man on prednisone and azathioprine for suspected chronic inflammatory demyelinating polyneuropathy . The organism was also cultured in the cerebrospinal fluid and urine and high cryptococcal antigen titers were found in the blood indicating systemic infection . The peritoneal catheter was removed, immunosuppression was withdrawn and he was treated with systemic antifungal therapy . He died suddenly nine weeks following the diagnosis and at post mortem was found to have evidence of cryptococcosis in lung, spleen and brain . The case demonstrates that cryptococcal peritonitis in patients on peritoneal dialysis should prompt a search for systemic infection and may require prolonged therapy. AIDS, 1994 Apr, 8(4), 423 - 9 Enhancement of HIV-1 replication in peripheral blood mononuclear cells by Cryptococcus neoformans is monocyte-dependent but tumour necrosis factor-independent; Orendi JM et al.; OBJECTIVE: To investigate the possible role of Cryptococcus neoformans in HIV-1 pathogenesis . DESIGN: An in vitro system was developed to study HIV-1 replication in freshly HIV-1-infected peripheral blood mononuclear cells (PBMC) incubated with whole azide-killed C . neoformans . METHODS: Human PBMC or peripheral blood lymphocytes were infected with lymphocytotropic HIV-1 and incubated with azide-killed encapsulated or non-encapsulated C . neoformans for 10 days . Viral replication was followed by HIV-1 p24 enzyme-linked immunosorbent assay and median tissue culture infective dose determination . Tumour necrosis factor (TNF) release by PBMC, induced by C . neoformans, was measured . Anti-TNF monoclonal antibodies or pentoxifylline were used to inhibit TNF bioactivity . RESULTS: Both encapsulated and non-encapsulated C . neoformans enhanced HIV-1 replication in PBMC but not in peripheral blood lymphocytes . C . neoformans induced TNF release by PBMC . Inhibition of TNF bioactivity did not block C . neoformans-enhanced HIV-1 replication in PBMC . CONCLUSIONS: C . neoformans can enhance HIV-1 replication in T cells only in the presence of monocytic cells . This enhancement is not dependent on encapsulation nor can it be attributed to TNF release. Yeast, 1994 Apr, 10(4), 475 - 9 NADH: ubiquinone oxidoreductase in obligate aerobic yeasts; Buschges R et al.; The strictly aerobic yeasts Candida pinus, Cryptococcus albidus, Rhodotorula minuta, Rhodotorula mucilaginosa and Trichosporon beigelii possess mitochondrial NADH dehydrogenases with significant features of the NADH:ubiquinone oxidoreductase (complex I) . These species show in all growth phases and under standard cultivation conditions, NADH dehydrogenases of approximately 700 kDa, which are sensitive to rotenone, a specific inhibitor of this complex . Identical results were obtained with the weakly fermenting C . pinus . The facultatively fermenting yeasts Saccharomyces cerevisiae and Kluyveromyces marxianus do not possess the 700 kDa-complex and are insensitive to rotenone . In S . cerevisiae, a rotenone-insensitive NADH dehydrogenase of about 500-600 kDa is detected only in stationary phase cells . As in Neurospora crassa, upon incubation of the obligately aerobic yeast R . mucilaginosa with chloramphenicol, an intermediate NADH dehydrogenase of approximately 350 kDa was formed, which was insensitive to rotenone. J Pharm Sci, 1994 Mar, 83(3), 404 - 6 Antimicrobial properties of alkaloids from Xanthorhiza simplicissima; Okunade AL et al.; The organic extract of the whole plant Xanthorhiza simplicissima was found to exhibit good activity against the AIDS-related opportunistic pathogens Candida albicans, Cryptococcus neoformans, and Mycobacterium intracellularae . Bioassay-directed fractionation of the extract led to the isolation of the known alkaloid berberine as the major active component . A second alkaloid of the isohomoprotoberberine family, puntarenine, was isolated from this plant family for the first time . Puntarenine also showed marginal activity against the dermatophytic fungus Trichophyton mentagrophytes and the yeast Saccharomyces cerevisiae. Antimicrob Agents Chemother, 1994 Mar, 38(3), 580 - 7 Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphotericin B; Mukherjee J et al.; The therapeutic efficacy of the immunoglobulin G1 (IgG1) monoclonal antibody (MAb) 2H1 to the Cryptococcus neoformans capsular polysaccharide was studied with and without amphotericin B (AmB) in a murine model of intravenous (i.v.) infection . MAb and AmB were administered by intraperitoneal (i.p.) injection after i.v . infection with a C . neoformans serotype D strain . Intraperitoneal administration of MAb 2H1 resulted in rapid distribution to the intravascular compartment, and the half-lives of i.p . and i.v . administered MAb were similar . Administration of MAb 2H1 alone resulted in increased survival, decreased lung fungal burden, and reduced serum glucuronoxylomannan antigen levels when given 2 to 6 h but not 24 h after infection . In vivo, the combination of MAb 2H1 and AmB was more effective at prolonging survival than either agent alone . MAbs of IgM, IgG1, IgG3, and IgA isotypes given 1 day after infection were effective in reducing serum GXM-D levels, with their relative efficacy being IgG1 > IgG3 > IgM > IgA . In vitro, MAb 2H1 was a potent opsonin of C . neoformans and the combination of MAb 2H1 and AmB was more effective than either agent alone in decreasing C . neoformans colony counts in the presence of the murine macrophage cell line J774.16 . The results confirm that capsule-binding MAbs can enhance the effect of AmB against C . neoformans and provide support for considering combined therapy in humans. J Clin Microbiol, 1994 Mar, 32(3), 848 - 50 Potential use of BacT/Alert automated blood culture system for antifungal susceptibility testing; Hazen KC et al.; A simple, rapid susceptibility test is needed to determine the possible resistance of yeasts to commonly used antifungal agents . The BacT/Alert automated blood culture system was evaluated as one technology for development of such a test . Yeast nitrogen base was used as the growth medium, and amphotericin B was the test antifungal agent . Isolates of various Candida species, Torulopsis glabrata, Saccharomyces cerevisiae, and Cryptococcus neoformans were evaluated . The results suggest that detection of amphotericin B resistance of yeast isolates within 12 to 14 h after inoculation of test medium is possible. Nihon Kyobu Shikkan Gakkai Zasshi, 1994 Mar, 32(3), 283 - 7 {A case of lung cancer with cryptococcal infection in resected lymph nodes}; Oshikawa K et al.; A 68-year-old female was admitted because of an abnormal shadow on chest X-ray film . Chest CT showed a nodular shadow in right S3a . Right upper lobectomy with mediastinal lymph node resection was performed under a diagnosis of lung cancer made by TBLB . Pathological examination of the resected lung revealed well differentiated adenocarcinoma . In addition, examination of the resected lymph nodes showed granulomas, some of which contained numerous cryptococci and showed central caseous necrosis, and others showed non-caseating epithelioid cell granulomas suggesting sarcoid reaction . No cryptococcal infection was found in the resected lung . Mediastinal lymph node involvement of cryptococcus in this case was considered to be the lymph node component of the primary pulmonary complex of cryptococcosis . Such a primary complex was demonstrated in 1% of the cases of cryptococcosis in previous reports. Arch Bronconeumol, 1994 Mar, 30(3), 166 - 9 {Pleural effusion as the only manifestation of cryptococcosis in an AIDS patient}; Garcia Garcia JC et al.; Cryptococcosis is often seen in immunodeficient patients, including those with AIDS . It usually affects mainly the respiratory tract and central nervous system . We present a rare case of pleural involvement with no sign of disease at other sites . A review of the literature yields only three other similar cases . We discuss the diverse clinical manifestations of cryptococcosis, particularly those found in the respiratory tract. Jpn J Antibiot, 1994 Mar, 47(3), 280 - 8 {Experience of fluconazole granules and injection in pediatric patients}; Kamiya H et al.; Fluconazole (FLCZ) is an antifungal agent of triazole class and has been proven to be effective against deep-seated mycosis caused by Candida spp., Aspergillus spp . and Cryptococcus spp . This time, as we had an opportunity to use fluconazole granules, a new dosage form of the agent, we investigated its efficacy and safety in children with deep-seated mycosis together with the efficacy of the injectable form of the agent . FLCZ was administered to 6 patients with fungal infections for treatment and 5 compromised hosts with a high risk of fungal infections for evaluation of its prophylactic effect . The patients enrolled in the study were 11 in total, of whom 6 patients were evaluated for efficacy: fungal phlegmon in 2, esophageal candidiasis in 2, fungal bronchitis in 1 and oral mycosis in 1 . Causative fungi for those infections were Candida albicans in 4 patients, Aspergillus, fumigatus in 1 and Aspergillus flavus in 1 . The clinical efficacies were excellent in 3 patients and good in 3 . The mycological efficacies were rated as eradicated in 5 patients and reduced in 1 . In 5 patients to whom FLCZ was given prophylactically, development of neither fungal infection nor unknown fever was noted . No side effects nor clinical laboratory abnormalities were observed during treatment with either granules or injection, indicative of its safety in children. Appl Environ Microbiol, 1994 Mar, 60(3), 927 - 31 Production of antibacterial compounds by phylloplane-inhabiting yeasts and yeastlike fungi; McCormack PJ et al.; The production of antibacterial compounds by yeasts and yeastlike fungi isolated from the phylloplane is reported . Aureobasidium pullulans, Citeromyces matritensis, Cryptococcus laurentii, Rhodotorula glutinis, and Sporobolomyces roseus produced antibacterial compounds inhibitory to both Pseudomonas fluorescens and Staphylococcus aureus in an overlay bioassay . In contrast, isolates of Candida albicans, Filobasidium uniguttulatum, Saccharomyces cerevisiae, Torulaspora delbruckii, Tremella foliacea, Trichosporon beigelii, and Trichosporon dulcitum obtained from soil or from culture collections did not produce inhibitory compounds when screened by the same procedure . The production of antibacterial compounds was examined in more detail, using several isolates of A . pullulans distinguished by cluster analysis on the basis of biochemical and physiological tests . They were found to produce a range of antibacterial compounds with different activities . Two distinct antibiotics were produced by an isolate of A . pullulans in liquid culture during both the logarithmic and the stationary phases of growth. Rinsho Byori, 1994 Mar, 42(3), 257 - 64 {Hypersensitivity pneumonitis--histopathology of summer-type hypersensitivity pneumonitis}; Kikui M et al.; Summer-type hypersensitivity pneumonitis(SHP) first reported by T . OCHI, et al . (1978), as a new type hypersensitivity pneumonitis(HP) with features of initiation during summer and anti-Cryptococcus antibody positive sera, has been recognized as "a unique disease in Japan", a most common type of HP in Japan, and now also known as anti-Trichosporon cutaneum antibody-positive SHP . This report was mainly concerned with the histopathology of SHP, thus far diagnosed in our hospital . Of the cases in our hospital, 62 consecutive biopsied cases (3 cases of open lung biopsy and 59 cases of transbronchial lung biopsy) without steroid institution before lung biopsy have been reviewed and revealed granulomatous interstitial pneumonitis in the bronchiolo-alveolar region, like various types of HP . Alveolitis (61 of 62 cases; 98.4%), sarcoid-like granuloma (50 of 62; 80.6%) and Masson's body (36 of 62; 58.1%) are main features, and could be named "triad" features . Concerning histopathological findings related with the period of lung biopsy after onset of clinical episodes as HP, alveolitis has been present regardless of period, and fibrinous exudate present in the early period and not in a case at 4 months . Sarcoid-like granuloma and Masson's body have appeared firstly at one-month cases . After this period sarcoid-like granuloma have been present in nearly all cases, but Masson's body has been not present in 10-month case with gradual decrease after 2 months, when all 2-month cases had it . In summary, for histopathological diagnosis of HP, the "triad" features and the time of lung biopsy done are keys, taking into consideration histopathological differential diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) J Med Microbiol, 1994 Mar, 40(3), 165 - 9 Pyrolysis typing of isolates from a recurrence of systemic cryptococcosis; Magee JT et al.; Cryptococcal meningitis was diagnosed in a 71-year-old male diabetic patient with underlying ischaemic heart disease, asthma and bilateral axillo-femoral vascular grafts . After treatment with fluconazole for 2 months, the patient appeared to be cured . Two years later he presented with an aneurysm of the right graft that was resected and replaced with a new graft segment . Cryptococcus neoformans var . neoformans was grown from post-operative blood cultures and samples of the excised graft . The patient was treated with fluconazole and discharged after 6 weeks . Multiple isolates from both episodes had been preserved, and these, together with isolates from other UK patients, were cultured in duplicate, blind coded and characterised by pyrolysis mass spectrometry (PMS) . Duplicate culture and re-isolate sets formed tight clusters, with each patient set clearly distinct . Sets of isolates from the two episodes in this patient formed a single tight cluster and were indistinguishable by PMS . These results support the contention that C . neoformans infection can be reactivated after being dormant for a prolonged period. Infect Immun, 1994 Mar, 62(3), 1079 - 88 Monoclonal antibodies to Cryptococcus neoformans capsular polysaccharide modify the course of intravenous infection in mice; Mukherjee S et al.; Immunoglobulin G1 (IgG1) monoclonal antibodies (MAbs) to the capsular glucuronoxylomannan (GXM) were studied for their ability to modify the course of intravenous Cryptococcus neoformans infection in mice . A/J mice were given intraperitoneal injection of 1.0 mg of either a GXM-binding IgG1 MAb (2H1 or 2D10 gamma 1) or the irrelevant isotype-matched control MAb 36-65 prior to intravenous infection . Parameters used to study antibody efficacy were lung and brain tissue fungal burden, lung and brain weights, serum GXM levels, and histopathological examination of lung, brain, heart, kidney, and spleen tissues . Mice given GXM-binding MAb had significantly reduced lung tissue fungal burden as measured by CFU . In contrast to the reduction in lung tissue burden, the reduction in brain tissue burden was small and did not achieve statistical significance . Serum GXM levels were reduced in mice receiving GXM-binding MAb . Histopathological examination revealed reduced numbers of granulomas and C . neoformans organisms in the lungs, brains, and kidneys of MAb 2H1-treated mice relative to control mice . The lungs and brains of mice receiving GXM-binding MAb weighed significantly less than those of control animals, consistent with the reduced inflammation noted histologically . Subendocardial inflammation and kidney cortical infarctions were present in control infected mice but not in MAb 2H1-treated mice . Immunocytochemical staining for polysaccharide antigen revealed a marked reduction in the amount of tissue polysaccharide in mice treated with MAb 2H1 relative to control mice . The results support an useful role for passive antibody administration in C . neoformans infections. Clin Exp Dermatol, 1994 Mar, 19(2), 181 - 4 Cutaneous cryptococcal infection without immunodeficiency; Gordon PM et al.; A case of cutaneous cryptococcosis (encapsulated strain) in a 67-year-old female, with no evidence of immune suppression (normal cell surface marker analysis and mitogen proliferation studies) and which responded to treatment with oral fluconazole is reported . To date her clinical progress remains satisfactory after 12 months of follow-up. Microbiology, 1994 Mar, 140 ( Pt 3), 543 - 50 Comparison of the electrophoretic karyotypes and chromosomal location of ten genes in the two varieties of Cryptococcus neoformans; Wickes BL et al.; We compared multiple isolates of the two varieties of Cryptococcus neoformans, as well as previously characterized representative isolates, for their electrophoretic karyotypes using pulsed-field electrophoresis . The two varieties could be clearly distinguished based upon the size of the smallest chromosome . The smallest chromosome for isolates of the gattii variety (serotypes B and C) was found to be 400-700 kb in size . The smallest chromosome for isolates of the neoformans variety was consistently found to be larger, approximately 770 kb in size . Isolates of the gattii variety averaged 13 chromosomes while the neoformans variety averaged 12 . The size of the Cryptococcus genome was found to be approximately 23 megabases . Isolates of C . neoformans var . neoformans tended to be more conserved than those of var . gattii with regard to gene position. Clin Infect Dis, 1994 Mar, 18(3), 369 - 80 Clinical epidemiological study of 171 cases of cryptococcosis; Rozenbaum R et al.; We retrospectively studied 171 patients with cryptococcosis who were divided into three groups according to their associated predisposing conditions (if any): group 1 comprised nonimmunosuppressed patients, group 2 comprised patients with AIDS, and group 3 comprised those patients with other conditions and/or who were users of immunosuppressive drugs . Analysis and correlation of the behavior of the mycosis among the three groups showed differences in the demographic data, clinical forms and manifestations of cryptococcosis, laboratory results, morbidity and mortality rates, and histopathologic aspects . Study of the clinical isolates of Cryptococcus neoformans from 83 patients with cryptococcosis showed that 75 were characterized as C . neoformans variety neoformans and eight as C . neoformans var . gatti . Comparison of the distribution of the gattii and neoformans varieties between the nonimmunosuppressed (group 1) and immunosuppressed (groups 2 and 3) patients showed a significant statistical difference (P < .01). Rev Inst Med Trop Sao Paulo, 1994 Mar-Apr, 36(2), 125 - 30 {Association of yeasts of the Cryptococcus genus with Eucalyptus species in Santafé de Bogotá}; Duarte A et al.; Environmental isolation of Cryptococcus neoformans var . gattii was first made in Australia in 1989 by ELLIS . He established a specific association with the tree species Eucalyptus camaldulensis and E . tereticornis . Based on his findings, ELLIS proposed that the fungus could be exported from Australia to others regions, including Colombia, by means of infected seeds . The purpose of this study was to isolate and identify Cryptococcus sp., associated with Eucalyptus trees; this is the first ecological evaluation of C . neoformans var . gattii in our country . A total of 100 Eucalyptus trees, distributed among 13 zones, located in the center, northeast, east and west of Santafe de Bogota, were studied . Flowers, fruits, leaves, barks and Eucalyptus debris were collected . The samples were processed by extraction with saline solution containing antibiotics, cultured in selective media and the isolates were identified by morphological and biochemical characteristics . Twenty-seven isolates of 9 Cryptococcus sp . were recovered from 21 Eucalyptus trees, from 5 zones . One C . neoformans var . neoformans serotype A was recovered . The Cryptococcus associated with Eucalyptus is important because this is the first study done in our country. Infection, 1994 Mar-Apr, 22(2), 137 - 42 Lipid-based amphotericin B in the treatment of cryptococcosis; Viviani MA et al.; Amphotericin B is the only antifungal drug which, despite its dose-limiting toxicity, can be given intravenously when an aggressive treatment is required . In an attempt to reduce the drug toxicity while retaining its therapeutic efficacy, new formulations of amphotericin B have been developed . The most promising have employed lipid vehicles such as liposomes . Three lipid-based amphotericin B formulations have been developed by pharmaceutical companies and are under active clinical investigation . Efficacy and safety data of these derivatives in animals and humans are reviewed, with particular concern to cryptococcal infection . The authors' experience with a small unilamellar liposomal amphotericin B formulation, AmBisome, in the primary therapy of cryptococcosis is reported . Nine AIDS patients affected with cryptococcosis, seven of whom had meningitis, were given AmBisome (3 mg/kg/day) for 3-6 weeks . Complete response was obtained in six patients, marked improvement in two, and failure in one . AmBisome was well tolerated and shortened the time to clinical and mycological response suggesting a further improvement in the management of cryptococcosis in AIDS patients. Antimicrob Agents Chemother, 1994 Mar, 38(3), 460 - 4 Cytokine treatment of central nervous system infection: efficacy of interleukin-12 alone and synergy with conventional antifungal therapy in experimental cryptococcosis; Clemons KV et al.; Cell-mediated immune responses appear to be critical in the outcome of cryptococcosis . Interleukin-12 (IL-12) was studied for its potential use as a therapeutic agent because of its stimulation of natural killer cells and gamma interferon production by stimulated T cells and natural killer cells . Gamma interferon-activated macrophages are important in host resistance against cryptococcosis . In two separate studies, male BALB/c mice were infected intravenously with Cryptococcus neoformans . In the first study, mice received either no treatment, 5.0 mg of fluconazole alone per kg of body weight per day (by gavage twice daily), or IL-12 subcutaneously at 0.01, 0.1, or 1.0 microgram/day once daily (low-dose study) alone or in combination with 5.0 mg of fluconazole per kg/day . In a second study (high dose), the dosages of IL-12 used were 1.0, 2.5, or 5.0 micrograms/day . Therapy was given for 10 consecutive days, and the number of CFU of C . neoformans remaining in various organs was quantitated 1 or 2 days after administration of the last dose . In the low-dose study, IL-12 at 0.1 or 1.0 microgram reduced the level of brain infection by approximately 10-fold (P < 0.05) and IL-12 at 1.0 or 0.1 microgram/day enhanced the efficacy of fluconazole . In liver, both the efficacy of IL-12 alone (0.01 or 0.1 microgram; P < 0.05) and enhancement of the efficacy of fluconazole (P < 0.05) were seen . No efficacy of IL-12 was seen in spleens or lungs, although spleen weights increased fourfold in mice given 1.0 microgram of IL-12 per day . In the high-dose study, all IL-12 doses alone again reduced the levels of brain infection (5- to 8-fold; P < 0.05) when the two were given in combination . No overt toxicities were observed at any dose, and overall, 1.0 microgram of IL-12 per day was found to be the optimal dosage for reducing infection in the brain . To our knowledge, this is the first demonstration of the efficacy of cytokine therapy in systemic and particularly brain infections with C . neoformans . The stimulation of cell-mediated immunity represents a new approach to therapy and can enhance suboptimal antimicrobial chemotherapy . IL-12 should be considered for further study and for clinical trials . These studies suggest that other opportunistic central nervous system pathogens should also be investigated. J Immunol, 1994 Mar 1, 152(5), 2344 - 50 CD4+ T cell-dependent acquired state of immunity that protects the brain against Cryptococcus neoformans; Hill JO et al.; In immunodeficient hosts, a failure in defense mechanisms allows Cryptococcus neoformans to establish foci of infection in the brain . Immune and nonspecific responses in the primary site of infection in the lung have been described, but those extrapulmonary defense mechanisms that can be mobilized against the yeast have received little attention . This paper describes a response expressed against yeast in the brain of immunocompetent hosts, a response that is weakened in hosts deficient in CD4+ T cells . When a small number of yeast gain access to the vasculature, for example through an i.v . injection, about 0.1% establish themselves in the brain . Normal mice but not SCID mice have the capacity to suppress the multiplication of these yeast cells . The host response is accelerated in mice that are recovering from a primary lung infection, resulting in long term survival without antibiotic chemotherapy . This response is ablated by anti-CD4 mAb treatment and CD4+ cells obtained from infected primed donors are needed to confer immunity on SCID recipients . The critical target for the anti-Cryptococcus immune response are yeast in the brain cortex . However, rather than preventing the colonization of the brain by blood-borne yeast, immunity apparently serves to restrict the growth of yeast in a small number of established foci. Med Clin (Barc), 1994 Feb 12, 102(5), 161 - 4 {Incidence and etiology of viremia in 2,619 patients}; Caballero Requero E et al.; BACKGROUND: Virus investigation, specially cytomegalovirus (CMV), in blood has increased such that the capacity of hospitalary laboratories is threatened with collapse . The causal agents of viremia are analyzed being correlated with the clinical symptoms and underlying disease to establish the selection criteria of patients for virologic study . METHODS: Two thousand six hundred nineteen patients suspected of having viral infection, fundamentally by CMV were studied over 6 years by 4,394 blood samples . Of these patients 1,646 were immunosuppressed, 824 were considered immunocompetent and this data was unknown in 149 patients . The leukocytes were separated using standardized techniques being seeded in cell cultures (human embryo lung fibroblasts) . RESULTS: Three hundred forty-seven specimens corresponding to 242 patients were positive with isolation of the following pathogens: 327 strains of CMV, 4 enterovirus, 2 adenovirus, 1 herpes simplex virus, 1 varicella-zoster, another 5 unidentified cytopathic agents, 6 strains of toxoplasma and 1 Cryptococcus . With regard to the base disease, 302 positive samples to CMV pertained to 204 immunosuppressed patients: 103 (13.6% positives among the cases studied) AIDS or AIDS-related complex, 54 (21.3%) kidney transplant patients, 31 (24.8%) liver transplant patients, 2 (1.5%) lung transplant patients, and 2 (1.5%) bone marrow transplant patients . A non CMV microorganism was isolated in 13 samples from 12 immunosuppressed patients . Only 24 (2.5% of those studied) immunocompetent or with unknown immunity status had viremia by CMV, being detected in 25 samples . Non CMV cytopathic agents were isolated in another 7 samples from 6 patients . CONCLUSIONS: Analysis of blood cultures allows the isolation of cytomegalovirus and occasionally other unsuspected agents such as toxoplasma . This investigation is indicated in immunosuppressed patients but not in immunocompetent patients who present a febrile syndrome with no clinical suspicion of cytomegalovirus infection. Arch Pathol Lab Med, 1994 Feb, 118(2), 194 - 5 Granulomatous peritoneal cryptococcomas . An unusual sequela of disseminated cryptococcosis; Gordon SM et al.; We report an unusual case of fibrosing peritoneal cryptococcal granulomas in a 36-year-old human immunodeficiency virus-negative man with small-bowel obstruction who previously had been treated for cryptococcal meningitis . At laparotomy, multiple pinhead-sized granulomas studded the visceral peritoneum . Microscopic examination showed cryptococcal granulomas characterized by peripheral fibrosis and central caseous necrosis . On mucicarmine staining, the rare teardrop budding and prominent capsular staining were characteristic of Cryptococcus species . We surmise that this inflammatory reaction observed in the peritoneum represents a chronic tissue reaction that occurred during the previous cryptococcal infection. J Bacteriol, 1994 Feb, 176(3), 656 - 64 Biochemical and molecular characterization of the diphenol oxidase of Cryptococcus neoformans: identification as a laccase; Williamson PR; Melanin production is a major virulence factor for Cryptococcus neoformans, an organism causing life-threatening infections in an estimated 10% of AIDS patients . In order to characterize the events involved in melanin synthesis, an enzyme having diphenol oxidase activity was purified and its gene was cloned . The enzyme was purified as a glycosylated 75-kDa protein which migrated at 66 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after deglycosylation by endoglycosidase F . Substrate specificity resembled that of a laccase in that it oxidized multiple diphenolic and diamino compounds . Dopamine was shown by mass spectroscopy to be oxidized to decarboxy dopachrome, an intermediate of melanin synthesis . The enzyme contained 4.1 +/- 0.1 mol of copper per mol . It resembled a laccase in its absorbance spectrum, containing a peak of 610 nm and the shoulder at 320 nm, corresponding to the absorbance of a type I and type III copper, respectively . The cloned gene of C . neoformans laccase (CNLAC1) contained a single open reading frame encoding a polypeptide 624 amino acids in length . The encoded polypeptide contained a presumptive leader sequence, on the basis of its relative hydrophobicity and by comparison of the sequence to that of the N-terminal sequence of the purified enzyme . CNLAC1 also contained 14 introns ranging from 52 to 340 bases long . Transcriptional activity of CNLAC1 was found to be derepressed in the absence of glucose and to correspond to an increase in enzymatic activity. J Bacteriol, 1994 Feb, 176(3), 651 - 5 Regulation of mannitol biosynthesis and degradation by Cryptococcus neoformans; Niehaus WG et al.; Cryptococcus neoformans, an encapsulated yeast that is an opportunistic pathogen of AIDS patients, produced and secreted mannitol when incubated with an appropriate carbon source . Glucose, fructose, and mannose were good growth substrates and were converted to mannitol . Maltose and xylose were good growth substrates but were not converted to mannitol . Cells of C . neoformans that were grown on a non-mannitol-generating carbon source, such as peptone or xylose, were able to convert glucose to mannitol only after a prolonged lag period in the presence of glucose . It was concluded that the enzymes of the mannitol biosynthetic pathway were not constitutively expressed but were induced in response to glucose or to a glucose metabolite . Enzymes required to catabolize mannitol, however, were constitutively expressed . The production of mannitol was inhibited by anaerobiosis, by the respiratory poison rotenone, and by polyethylenesulfonate, a specific inhibitor of fungal NADP-dependent dehydrogenases . When cells were incubated with deuterated glucose, the deuterium content of the mannitol produced was much lower than that of the glucose precursor, indicating that the glucose was diluted by an intracellular pool of an intermediate . We had previously shown that C . neoformans contains a large intracellular pool of glucose 6-phosphate, and we now conclude that this pool of glucose 6-phosphate is metabolically active. Antimicrob Agents Chemother, 1994 Feb, 38(2), 378 - 80 In vitro susceptibility of the opportunistic fungus Cryptococcus neoformans to anthelmintic benzimidazoles; Cruz MC et al.; Ten benzimidazole derivatives and amphotericin B were tested in vitro against three isolates of Cryptococcus neoformans . Drug concentrations inhibiting 50% of growth (IC50s) were determined . Four derivatives, including mebendazole and albendazole, had moderately high activities (IC50 = 0.1 to 0.3 microgram/ml) . Fenbendazole, however, was 10-fold more active (IC50 = 0.01 to 0.02 microgram/ml) and also 2-fold more active than amphotericin B . Ten additional clinical isolates of C . neoformans were tested against fenbendazole, mebendazole, and albendazole; similar susceptibilities were observed . Drug concentrations lethal to 90% of the cells (LC90s) were determined for two isolates . The LC90s of albendazole and mebendazole were 0.92 to 2.1 micrograms/ml, and those of fenbendazole were 0.06 to 0.07 microgram/ml; the latter are eight to ninefold lower than the LC90s of amphotericin B that were obtained . Spontaneously arising mutants displaying partial resistance to fenbendazole arose at a low frequency (5 x 10(-9). Antimicrob Agents Chemother, 1994 Feb, 38(2), 294 - 9 Treatment of murine candidiasis and cryptococcosis with amphotericin B incorporated into egg lecithin-bile salt mixed micelles; Brajtburg J et al.; Amphotericin B (AmB) with deoxycholate (Fungizone) and AmB incorporated into mixed micelles (AmB-mixMs) composed of egg lecithin with glycocholate, deoxycholate, or taurocholate were compared as treatments for murine infections . For mice infected with Candida albicans, treatment consisted of a single intravenous injection; for mice infected with Cryptococcus neoformans, treatment consisted of two intravenous injections . The maximal tolerated doses of AmB as Fungizone were 1.25 mg/kg of body weight in mice with candidiasis and 2.5 mg/kg of body weight in mice with cryptococcosis . The AmB-mixMs were nontoxic to mice at doses of 80 and 100 mg/kg of body weight and were therapeutically more active than the maximal tolerated dose of Fungizone in both models of infection . However, when Fungizone or AmB-mixMs were administered at equivalent doses of AmB, AmB-mixMs were more active in treating murine candidiasis, whereas Fungizone was more active in treating murine cryptococcosis. Antimicrob Agents Chemother, 1994 Feb, 38(2), 177 - 83 In vitro renal toxicity and in vivo therapeutic efficacy in experimental murine cryptococcosis of amphotericin B (Fungizone) associated with Intralipid; Joly V et al.; We compared the experimental toxicities and activities of deoxycholate amphotericin B (d-AmB) dissolved in glucose (Dd-AmB) or mixed with 20% Intralipid (ILd-AmB) . In vitro, ILd-AmB against renal tubular cells in primary culture . In vivo, the toxicities and activities of Dd-AmB and ILd-AmB were studied in DBA2 mice with cryptococcosis . The maximum tolerated dose of intravenously administered d-AmB, i.e., the dose that induced less than 15% mortality because of toxicity, was 1.7 to 2.5 times higher when it was administered as ILd-AmB than when it was administered as Dd-AmB . Both treatments given intravenously at the same dose were equivalent for improving the survival of mice and reducing CFU counts in infected tissue, but at maximum tolerated doses, ILd-AmB (2 mg/kg of body weight) was more effective than Dd-AmB (0.8 to 1.2 mg/kg) . AmB concentrations in spleen, liver, lung, and kidney were measured by high-pressure liquid chromatography 4 and 24 h after a single injection of 1.2 mg of Dd-AmB per kg, 1.2 mg of ILd-AmB per kg, or 2 mg of ILd-AmB per kg . In a given organ, AmB levels were similar after administration of 1.2 mg of Dd-AmB or ILd-AmB per kg but were significantly higher after administration of 2 mg of ILd-AmB per kg . The lower level of toxicity of ILd-AmB might be explained by circular dichroism experiments, showing that ILd-AmB contained 10-fold less soluble oligomeric AmB, which is believed to be the toxic form of the drug, than Dd-AmB . We conclude that ILd-AmB is as efficient as Dd-AmB and is better tolerated than Dd-AmB in mice with experimental cryptococcosis . By allowing higher doses of AmB to be infused, Intralipid enhances AmB concentrations in infected sites, and thus the therapeutic activity of the drug. J Clin Microbiol, 1994 Feb, 32(2), 554 - 6 Diagnosis of paracoccidioidomycosis by dot immunobinding assay for antibody detection using the purified and specific antigen gp43; Taborda CP et al.; The dot immunobinding assay, a rapid, visually read test, was adapted for serodiagnosis and follow-up of paracoccidioidomycosis (PCM) . Purified gp43 antigen was tested before and after sodium metaperiodate treatment . To evaluate the assay, it was tested with sera from PCM, histoplasmosis, Jorge Lobo's disease, aspergillosis, candidiasis, and cryptococcosis patients and healthy subjects . Native gp43 gave positive results with all sera from PCM patients and weakly positive results with sera from Jorge Lobo's disease patients (31.3%) . No false-positive results were obtained when periodate-treated gp43 was used as the antigen . These results indicate that the dot immunobinding test is sensitive, specific, economical, and fast for serodiagnosis and follow-up studies of PCM. Rev Med Interne, 1994 Feb, 15(2), 116 - 9 {Pulmonary nocardiosis in a HIV positive African patient}; Tissot B et al.; Case report of a pulmonary nocardiosis associated with a pneumocystosis pneumonia and a cryptococcal meningitis in an African not already known as infected with Human Immunodeficiency Virus . Fever reoccurred when cotrimoxazole was stopped for intolerance . Bronchoalveolar lavage gave diagnosis. Mycopathologia, 1994 Feb, 125(2), 77 - 81 Serotypes and mating types of clinical strains of Cryptococcus neoformans isolated in Taiwan; Hsu MM et al.; Twenty-one strains of Cryptococcus neoformans isolated from patients in Taiwan were characterized for serotypes and mating types . Slide agglutination test was performed with 8 factor-specific sera (Iatron Company, Japan) to determine the serotypes . Wheat bran agar (WBA) and malt extract agar (MEA, Wickerham) media were used for the mating tests . Twenty of the isolates were of serotype A, and one was serotype B . Except for 2 strains of serotype A, all of the serotype A strains mated with Filobasidiella neoformans var . neoformans, mating type a . The only serotype B strain mated with F . neoformans var . bacillispora mating type a in MEA medium . These data revealed the low prevalence (1/21; 4.8%) of C . neoformans var . gattii in Taiwan, a subtropically located isoland. Arq Bras Cardiol, 1994 Feb, 62(2), 95 - 8 {Clinicopathologic correlation in 50 cases of acquired immunodeficiency syndrome . Retrospective study}; Herdy GV et al.; PURPOSE--To analyze myocardial abnormalities in patients of acquired immunodeficiency syndrome with clinical and pathological correlation . METHODS--We selected 50 cases, retrospectively, age ranged from 3 months to 40 years, all of them had myocardial changes and the data of clinical records fulfilled our protocol . Cases of others cardiac diseases were not included . RESULTS--The pathological findings were: myocarditis in 33 (11 had severe myocarditis) and degenerative hystological lesions in 17 . The etiologic agents detected were: Toxoplasma in 11, Cryptococcus in 7 and Cytomegalovirus in 3 . In 12 cases we could not find any agent . In 15 cases occurred others lesions: endocarditis, pericarditis and sarcoma of Kaposi . It was noted tachycardia in 15 cases, decrease of heart sounds in 12, arterial hypotension in seven, systolic murmur in 8, galop rhythm in 7, pericardial friction rub in 3, arrhythmia in 2 . Four patients had congestive heart failure . The EKG showed sinus tachycardia in 18, ST and T changes in 10, low voltage in 5, ST segment elevation in 5 and extrasystoles in 3 cases . The echocardiogram findings were: pericardial effusion in 9 cases and 9 had ventricular dysfunction . CONCLUSION--The cardiac lesions were very important even in patients without clinical signals . We need others prospective studies with viral identification trying to detect specific lesions of HIV. Cutis, 1994 Feb, 53(2), 88 - 90 Cutaneous cryptococcosis with molluscum contagiosum coinfection in a patient with acquired immunodeficiency syndrome; Sulica RL et al.; We report the first patient with acquired immunodeficiency syndrome in whom molluscum contagiosum and Cryptococcus neoformans were documented in the same cutaneous lesion . While cases of the co-occurrence of two pathologic entities in patients with acquired immunodeficiency syndrome have been reported, namely cytomegalovirus with herpes simplex virus and Kaposi's sarcoma with Histoplasma capsulatum, the findings in this patient are unique . The clinical presentation of cutaneous lesions caused by molluscum contagiosum and by Cryptococcus neoformans is reviewed . The findings in this case are more remarkable still given the often-noted tendency of cutaneous cryptococcosis to masquerade as molluscum contagiosum . It may be that the lesions of molluscum contagiosum create a favorable environment for cryptococcal dissemination . Examination of a biopsy specimen is crucial to the diagnosis of skin lesions, often atypical or deceptive, in immunosuppressed patients. J Biol Chem, 1994 Jan 28, 269(4), 2996 - 3009 Comparison of myristoyl-CoA:protein N-myristoyltransferases from three pathogenic fungi: Cryptococcus neoformans, Histoplasma capsulatum, and Candida albicans; Lodge JK et al.; Myristoyl-CoA:protein N-myristoyltransferase (Nmt) transfers myristate from CoA to the N-terminal Gly residue of cellular proteins in an ordered reaction mechanism that first involves binding of myristoyl-CoA to the apoenzyme . The gene encoding Saccharomyces cerevisiae Nmt1p (NMT1) is essential for vegetative growth . Candida albicans, Cryptococcus neoformans var . neoformans, and Histoplasma capsulatum are the principal causes of systemic fungal infections in immunocompromised humans . Metabolic labeling studies indicate that they synthesize a small set of cellular N-myristoylproteins during exponential growth on rich media, the most prominent of which co-migrate with two essential functionally interchangeable S . cerevisiae N-myristoylproteins, ADP ribosylation factor-1 (Arf1p) and Arf2p . NMT and ARF genes have been recovered from C . neoformans and H . capsulatum using the polymerase chain reaction . They are single copy genes, interrupted by multiple introns . C . neoformans and H . capsulatum Nmts have approximately 50% amino acid sequence identity with the orthologous S . cerevisiae, C . albicans, and Homo sapiens N-myristoyltransferases, whereas C . neoformans and H . capsulatum Arfs are approximately 80% identical with C . albicans Arf and S . cerevisiae Arf1p and Arf2p . Functional studies of C . neoformans and C . albicans Nmts conducted in Escherichia coli reveal that (i) both efficiently acylate S . cerevisiae Arf2p; (ii) C . neoformans Arf is a substrate for C . neoformans Nmt; and (iii) substitution of an Asp for a Gly located 5 residues from the C terminus of these two enzymes causes marked temperature-dependent reductions in their catalytic efficiency, just as it does with S . cerevisiae and H . sapiens Nmts . Wild type C . neoformans, C . albicans, and H . sapiens NMTs can fully complement the lethal phenotype of a S . cerevisiae nmt1 null allele at 24 and 37 degrees C when the GAL1-10 promoter controlling their expression is induced by galactose . Only the C . albicans enzyme is able to do so when the promoter is repressed with glucose . This complementation profile likely arises, at least in part, from differences in the protein substrate specificities of the orthologous Nmts . A Gly-->Asp mutation in S . cerevisiae, C . neoformans, C . albicans, and H . sapiens Nmts produces temperature-sensitive growth arrest in isogenic S . cerevisiae strains with a nmt1 null allele . Growth of strains producing the mutant C . albicans or H . sapiens, but not the C . neoformans, enzyme can be rescued by myristate at the non-permissive temperature (37 degrees C) even in the presence of cerulenin, an inhibitor of fatty acid synthetase.(ABSTRACT TRUNCATED AT 400 WORDS) N Engl J Med, 1994 Jan 27, 330(4), 263 - 72 Oral azole drugs as systemic antifungal therapy; Como JA et al.; The oral azole drugs--ketoconazole, fluconazole, and itraconazole--represent a major advance in systemic antifungal therapy . Among the three, fluconazole has the most attractive pharmacologic profile, including the capacity to produce high concentrations of active drug in cerebrospinal fluid and urine . Ketoconazole, the first oral azole to be introduced, is less well tolerated than either fluconazole or itraconazole and is associated with more clinically important toxic effects, including hepatitis and inhibition of steroid hormone synthesis . However, ketoconazole is less expensive than fluconazole and itraconazole--an especially important consideration for patients receiving long-term therapy . All three drugs are effective alternatives to amphotericin B and flucytosine as therapy for selected systemic mycoses . Ketoconazole and itraconazole are effective in patients with the chronic, indolent forms of the endemic mycoses, including blastomycosis, coccidioidomycosis, and histoplasmosis; itraconazole is also effective in patients with sporotrichosis . Fluconazole is useful in the common forms of fungal meningitis--namely, coccidioidal and cryptococcal meningitis . In addition, fluconazole is effective for selected patients with serious candida syndromes such as candidemia, and itraconazole is the most effective of the azoles for the treatment of aspergillosis. J Biol Chem, 1994 Jan 21, 269(3), 1858 - 64 Protein-polysaccharide interactions . A monoclonal antibody specific for the capsular polysaccharide of Cryptococcus neoformans; Otteson EW et al.; Monoclonal antibodies that react with the capsular polysaccharide, termed glucuronoxylomannan (GXM), of Cryptococcus neoformans have potential roles in the diagnosis, monitoring of disease progress, and immunotherapy of cryptococcal GXM of all four serotypes . A molecular model of the Fab fragment of monoclonal antibody 439 was constructed from the amino acid sequence and a template antibody molecule, Fab 4-4-20 . A tryptophan is present on the surface between light chain CDR3 and heavy chain CDR3 in the putative binding site . This tryptophan residue proved to be a reporter group, and a fluorescence study of Fab 439 was performed to analyze the interaction between cryptococcal GXM and Fab 439 . Binding of the polysaccharide enhanced the intrinsic fluorescence and caused a blue shift in the emission maximum, indicating that the environment of a tryptophan changes from a polar to less polar environment . This is consistent with the loss of water from the binding site caused by the binding of antigen . This interpretation was confirmed by acrylamide quenching, which showed that 1 less tryptophan was exposed to solvent in the Fab-GXM complex than in free Fab . Fluorescence titration was used to determine binding and dissociation constants (KD) . The apparent KD values for serotypes A-C were approximately the same; the KD for serotype D GXM was 5-11-fold greater . De-O-acetylation of serotype A GXM produced a 31-fold increase in the KD, indicating that the O-acetyl groups are important, but not essential, for binding . Carboxyl groups appear to be essential for strong binding because the KD for carboxyl-reduced GXM was so large that it could not be determined. J Immunol, 1994 Jan 15, 152(2), 724 - 34 Effect of granulocyte-macrophage colony-stimulating factor on rat alveolar macrophage anticryptococcal activity in vitro; Chen GH et al.; Cryptococcus neoformans, a pathogenic fungus usually acquired by inhalation, causes the most common lethal mycosis in AIDS . The resident lung phagocytes, alveolar macrophages (AM phi), inhibit growth of C . neoformans poorly unless activated by cytokines such as IFN-gamma . In this study, we examined the effect of rat AM phi of the potent hematopoietic and M phi-activating cytokine, granulocyte-macrophage CSF (GM-CSF), alone and in combination with other cytokines . Rat AM phi monolayers were preincubated with 0.1 to 1000 U/ml GM-CSF without or with other recombinant cytokines, and then were incubated with viable C . neoformans (strain H99/C3D) . Growth inhibition was assessed by counting cryptococcal CFU at 24 and 48 h of coculture; AM phi proliferation was assessed by measuring both uptake of {3H}TdR and AM phi numbers . AM phi preincubated with GM-CSF for 5 days (but not for shorter periods) inhibited growth of C . neoformans . Anticryptococcal activity required direct contact of AM phi with C . neoformans, but once induced by preincubation, did not require continued exposure to GM-CSF . Induction of anticryptococcal activity by GM-CSF was dose dependent (maximal induction at 250 U/ml), and was due to both increased ingestion and killing . GM-CSF induced AM phi proliferation, but anticryptococcal activity was not due totally to increases in AM phi numbers, indicating AM phi activation by GM-CSF . GM-CSF-induced AM phi proliferation was increased by IL-6, unchanged by IL-8, and abolished by LPS or IFN-gamma . However, IL-6 did not increase GM-CSF-induced anticryptococal activity . The combination of GM-CSF and IFN-gamma showed rapid and sustained anticryptococcal activity, unlike either cytokine alone . Our in vitro data suggest that the combination of GM-CSF and IFN-gamma may have beneficial effects on host defense against C . neoformans in vivo. Folia Microbiol (Praha), 1994, 39(6), 485 - 8 New search for pectolytic yeasts; Biely P et al.; A new screening method for pectin-depolymerizing microorganisms is described . The method is based on precipitation of non-hydrolyzed citrus pectin with hexadecyltrimethylammonium bromide in a medium solidified with a bacterial gelling gum . A substrate depolymerized by the secreted enzymes does not precipitate, and the positive strains thus show transparent areas around the colonies . The method was used to screen 300 yeast and yeast-like microorganisms belonging to 52 different genera . The secretion of pectin-depolymerizing enzymes occurred with different frequencies in 13 genera (69 positive strains of 207 tested), the lowest frequency being found in the genus Candida (13 positive out of 125 strains tested) and the highest frequency in the genera Aureobasidium (4 of 6) Cryptococcus (29 of 38), Geotrichum (4 of 9), Kluyveromyces (5 of 5), Rhodosporidium (2 of 2), Leucosporidium (2 of 2), Trichosporon (3 of 6) and Ustilago (2 of 2) . Strains giving the highest number of harvested cells after growth on pectin in a liquid medium have been identified. Infect Immun, 1994 Jan, 62(1), 215 - 20 Occurrences, specificities, and functions of ubiquitous antibodies in human serum that are reactive with the Cryptococcus neoformans cell wall; Keller RG et al.; Previous studies found that normal human serum (NHS) contains an immunoglobulin G (IgG) antibody that mediates initiation of the classical complement pathway by nonencapsulated Cryptococcus neoformans . The present study used an enzyme-linked immunosorbent assay with whole nonencapsulated yeast cells as solid-phase antigens to demonstrate the presence of high levels of IgG antibody in each of 11 sera from normal adult donors . The IgG antibodies were of the IgG2 subclass . The antibody activity was blocked completely by treatment of serum with isolated yeast glucan . Treatment of serum with mannan or chitin had no effect on antibody levels . Antibody activity was adsorbed completely by treatment of serum with zymosan particles . Adsorption with intact cells of Saccharomyces cerevisiae or Candida albicans had no effect, suggesting that the glucan on S . cerevisiae or C . albicans is not surface exposed . Assessment of the opsonic requirements for phagocytosis of nonencapsulated cryptococci by monocyte-derived human macrophages (MO-M phi) showed that high levels of phagocytosis occurred when yeast cells were opsonized with NHS . Removal of anti-glucan antibody by adsorption with whole nonencapsulated cryptococci did not diminish opsonic activity . Heat-inactivated serum or anti-glucan antibody affinity purified from NHS lacked opsonic activity . Taken together, these results indicate that phagocytosis of nonencapsulated cryptococci by monocyte-derived human macrophages has an obligatory requirement for opsonic ligands of the complement system, with no contribution by the anti-glucan IgG that is found in NHS. Infect Immun, 1994 Jan, 62(1), 194 - 202 Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans; Levitz SM et al.; Lymphocytes constitute a critical component of host defenses against cryptococcosis . Previously, we demonstrated that human lymphocytes cultured with interleukin-2 formed conjugates with, and directly inhibited the growth of, Cryptococcus neoformans . Here, we explore the anticryptococcal activity of freshly isolated, highly purified populations of human peripheral blood lymphocytes . Lymphocytes were incubated with encapsulated C . neoformans for 24 h, after which the lymphocytes were lysed, dilutions and spread plates were made, and CFU were counted . Fungistasis was determined by comparing growth in wells with and without lymphocytes . Nylon wool-nonadherent peripheral blood mononuclear cells (NWNA PBMC) were highly fungistatic, even if either T cells or natural killer (NK) cells were depleted by panning . A mixed population of T cells and NK cells, obtained by rosetting NWNA PBMC with sheep erythrocytes, completely inhibited cryptococcal growth, whereas the nonrosetting cells had little fungistatic activity . CD4+, CD8+, and CD16/56+ lymphocytes, isolated by positive immunoselection, had potent growth-inhibitory activity . In contrast, purified B cells had no activity . Fungistasis was seen even in the absence of opsonins . Antifungal activity was markedly diminished when surface receptors on NWNA PBMC were cleaved by treatment with trypsin or bromelain . Supernatants from stimulated lymphocytes or concentrated lymphocyte sonicates were not active . Lymphocyte-mediated fungistasis was seen with two different strains of C . neoformans . CD4+, CD8+, and CD16/56+ lymphocytes formed conjugates with C . neoformans, as observed under Nomarski differential interference contrast microscopy and videomicroscopy . These data demonstrate that freshly isolated peripheral blood T cells and NK cells have the capacity to bind and directly inhibit the growth of C . neoformans. Immunol Ser, 1994, 60, 533 - 43 Macrophage-Cryptococcus interactions; Levitz SM; Macrophages are a heterogeneous population that vary depending on their species of origin, anatomic location, state of activation, and conditions of culture . Moreover, macrophages normally interact with other cells both within and without the immune system . It is clear from the data reviewed in this chapter that all of these aforementioned variables greatly influence macrophage-C . neoformans interactions . While circumstantial evidence strongly supports a major role for the macrophage in host defenses against cryptococcosis, the nature and extent of the contribution macrophages make remain to be defined . One major challenge for researchers in this field will be to design experiments that closely mimic what occurs in human physiological and pathological states. J Thorac Imaging, 1994 Spring, 9(2), 78 - 84 Pulmonary manifestations of cryptococcosis in patients with AIDS: CT features; Sider L et al.; The computed tomographic (CT) scans and chest radiographs of 10 patients with AIDS and proven pulmonary cryptococcal infections were reviewed . In seven patients (70%), CT demonstrated pulmonary opacities that ranged in appearance from a perihilar interstitial pattern to an area of dense alveolar consolidation . Corresponding chest radiographs were less accurate in detecting interstitial opacities (2 of 5 patients, 40%) than the alveolar opacities (4 of 5 patients, 80%) . Pulmonary nodules were identified in three patients (30%) by CT but were identifiable on the chest radiograph in only one patient (10%) . The chest radiograph suggested hilar adenopathy in three patients although CT confirmed hilar adenopathy in only one patient . In one patient, a small pleural effusion, not appreciated on the chest radiograph, was detected by CT . CT may add additional information in the diagnosis of pulmonary Cryptococcus neoformans. J Indian Med Assoc, 1994 Jan, 92(1), 24 - 6 Opportunistic infection in AIDS; Sengupta D et al.; PIP: Opportunistic infections may be severe in people having acquired immunodeficiency syndrome (AIDS) . These infectious agents often demonstrate an uncommon persistence and may even show a recurring trait . This report describes 10 of the most commonly seen opportunistic infectious agents found in AIDS patients in India . The authors briefly describe the immunologically debilitating effects of AIDS in humans . A suggested treatment program including specific drugs to use against each pathogen is described . Further, the authors note that drug hypersensitivity developed in many AIDS patients . The 10 infections described are candidiasis, tuberculosis (TB), Pneumocystis carinii, cryptococcus, histoplasmosis, toxoplasmosis, cryptosporidiosis, Mycobacterium avium, Herpes simplex, and cytomegalovirus . Multiple infections were common . A regime of fluconazole is used against candidiasis and cryptococcus . Standard antituberculines are prescribed for TB . Amphotericin and flucytosine are effective against cryptococcus . Histoplasmosis is treated with amphotericin or itraconazole . Sulfadiazine sodium and pyrimethamine are given to toxoplasmosis patients . Cryptosporidiosis is treated with paramomycin . Acyclovir is effective against Herpes simplex . Cytomegalovirus is treated with foscarnet and ganciclovir . Dosages for each drug are also provided . Med Trop (Mars), 1994, 54(1), 53 - 5 {Ecology of Cryptococcus neoformans in central Africa}; Swinne D et al.; Cryptococcosis associated with AIDS is mainly due to Cryptococcus neoformans var . neoformans which is found in saprophytic form in pigeon droppings . This variety has been isolated in Central Africa, particularly in Zaire, Burundi and Rwanda, from dust collected from the houses of patients with cryptococcosis . Several patients confirmed frequent contact with pigeons . Recent studies in Australia demonstrated a link between the yeast and Eucalyptus of the camaldulensis and teriticornis species . These two species were imported to Central Africa from Australia . Examination of 657 Eucalyptus specimens collected in Rwanda did not detect the yeast in any type of tree . This finding casts doubt on the role of Eucalyptus in the ecology of cryptococcosis in Central Africa. Zhonghua Yi Xue Za Zhi (Taipei), 1994 Jan, 53(1), 58 - 61 Intramedullary cryptococcal granuloma of spinal cord: a case report; Su MC et al.; The budding yeast, Cryptococcus neoformans, is widely distributed throughout the world and causes opportunistic and non-contagious infections in man . Involvement of the central nervous system has been found in 70% of patients at the time of diagnosis, and meningitis or meningoencephalitis are the most common manifestations . Space-occupying cryptococcal granuloma, on the other hand, is infrequently encountered in the brain and extremely rare in the spinal cord . Seven cases of spinal torulomas (cryptococcal granuloma) have been reported in the available literature . Only one was intramedullary . Here an isolated case of intramedullary cryptococcal granuloma in the spinal cord in an immunocompetent patient is reported; diagnosis was by intraoperative frozen section . After two months of post-operative antifungal treatment, the clinical condition has received markedly improvement. J Infect, 1994 Jan, 28(1), 59 - 64 Cryptococcal meningitis in Lilongwe and Blantyre, Malawi; Maher D et al.; Infection with Human Immunodeficiency Virus is widespread in Malawi and cryptococcal meningitis is a common problem in those with AIDS . A review of microbiology laboratory records in Lilongwe and Blantyre between July 1991 and January 1993 identified 31 patients with cryptococcal meningitis . Diagnosis was based on a positive India ink stain of CSF and/or culture of Cryptococcus neoformans . There were 16 men (median age 38 years) and 15 women (median age 28 years) in the investigation . The median duration of symptoms was 2 weeks . The clinical presentation was varied, the most frequent features being headache (97%), neck stiffness (74%), fever (61%) and altered consciousness (58%) . CSF WBC count, glucose and protein concentrations were non-specific . Most patients could not afford anti-cryptococcal chemotherapy and their median survival time after diagnosis was 4 days . Patients who could afford such treatment survived for up to several months . Diagnosis is useful for prognostic reasons and may save patients unnecessary treatment if tuberculous meningitis is the alternative diagnosis . Cryptococcal antigen detection tests may improve diagnostic accuracy . The problem of cryptococcal meningitis is likely to become increasingly common as HIV infection becomes more widespreadPIP: In Malawi, a physician from Queen Elizabeth Central Hospital in Blantyre and one from Kamuzu Central Hospital in Lilongwe retrospectively analyzed laboratory records to determine the clinical features, cerebrospinal fluid (CSF) findings, treatment, and outcome of 31 patients with cryptococcal meningitis admitted to the hospitals between July, 1991, and January, 1993 . Cryptococcal meningitis is a common manifestation of cryptococcosis in people with AIDS . It has become prevalent in Malawi in the last 5 years . The incidence of cryptococcal meningitis cases among medical admissions at both hospitals was 0.1%/year . The median ages of the 16 men and 15 women were 38 and 28 years, respectively . Symptoms lasted from 1 day to 5 months (median, 2 weeks) . The leading signs and symptoms included headache (97%), neck stiffness (74%), fever (61%), altered consciousness (58%) . The records revealed nonspecific readings for CSF white blood cell count and glucose and protein concentrations . 81% of the cases did not receive antifungal chemotherapy because they could not afford it . None of these untreated patients survived longer than 30 days after diagnosis of cryptococcal meningitis . Most died within the 1st 4 days . In fact, the median survival time after diagnosis for all 31 patients was 4 days . The patients who could afford antifungal chemotherapy survived 4 to at least 9 months . Diagnosis helps clinicians to make more accurate prognoses and keeps them from prescribing unnecessary treatment, especially if tuberculosis meningitis is the other diagnosis . As the prevalence of AIDS increase in Malawi, so should cryptococcal meningitis . J Antimicrob Chemother, 1994 Jan, 33(1), 73 - 81 Amphotericin B lipid complex in the treatment of experimental cryptococcal meningitis and disseminated candidosis; Perfect JR et al.; In the quest for safer and more effective antifungal agents, amphotericin B (AMB) has been placed in a variety of lipid preparations . In this study, we examined the efficacy of amphotericin B lipid complex (ABLC) on experimental cryptococcal meningitis and disseminated candidosis . This formulation is relatively safe compared to the parent compound, and therefore doses ten times greater than the commercial amphotericin B deoxycholate can be given to rabbits . Although at equal doses the ABLC preparation is less potent than AMB, a higher dose of ABLC was rapidly fungicidal in the contexts of both a central nervous system infection with Cryptococcus neoformans during immune suppression, and a heart and kidney infection with Candida albicans . Rapid sterilization of tissue should be a goal of antifungal drug therapy, particularly in the immune compromised host . From these studies, this AMB lipid formulation has the ability to produce rapid fungicidal activity in vivo, but it requires higher doses than AMB deoxycholate . Clinical trials in humans must examine carefully the therapeutic-toxic ratio in dose-escalation protocols to determine the optimal dosage strategy for this agent. Dermatology, 1994, 188(2), 108 - 12 Spectrum of dermatological lesions in renal allograft recipients in a tropical environment; Chugh KS et al.; A total of 157 renal allograft recipients were followed for over 1-23 months for the development of dermatological lesions . The non-infective lesions related to immunosuppressive drugs included cushingoid features in 133 (84.7%), xerosis in 120 (76.4%), striae in 69 (43.9%), hypertrichosis in 65 (21.6%), facial erythema in 42 (26.7%) and friable skin in 34 (21.4%) patients . Of the infective lesions, cutaneous mycoses were the most frequent (82.6%) and included tinea corporis and cruris in 82 (52.2%), tinea versicolor in 21 (13.3%), candidiasis in 7 (4%), onychomycosis in 4 (2%) and cryptococcosis in 2 (1.2%) patients . Viral infections included those due to herpes zoster in 17 (10.8%), herpes simplex in 5 (3.1%) and viral warts in 13 (8.2%) patients . Cutaneous malignancy was seen in 1 patient only. J Clin Microbiol, 1994 Jan, 32(1), 253 - 5 Unique oligonucleotide primers in PCR for identification of Cryptococcus neoformans; Mitchell TG et al.; On the basis of a comparison of rRNA sequences coding the internal transcribed spacer (ITS) and 5.8S regions of Filobasidiella neoformans, the teleomorph of Cryptococcus neoformans, and members of its most closely related taxa, unique oligonucleotides were designed for the specific amplification of DNA only from C . neoformans . Various combinations of these primers, designated CN4, CN5, and CN6, and the previously described fungal primers ITS1 and ITS2 were tested in PCR for their ability to amplify DNA from 37 strains of C . neoformans and 31 other isolates representing 18 species of yeasts . The combination of primers CN4 and CN5 amplified DNA from both varieties of C . neoformans but from none of the other species tested . Other pairs of primers (namely, CN5-CN6, CN4-ITS1, and CN6-ITS1) amplified DNA only from C . neoformans and from the saprophyte Filobasidiella depauperata, which is the only other member of the genus Filobasidiella . With appropriate controls, these specific oligonucleotides may be used as primers in PCR to identify C . neoformans. Nihon Kyobu Shikkan Gakkai Zasshi, 1994 Jan, 32(1), 37 - 41 {Evaluation of (1-3)-beta-D-glucan in aspergillosis and cryptococcosis}; Mitsutake K et al.; (1-3)-beta-D-Glucan (beta-glucan) is a major structural component of fungi . The G test is a direct method to detect beta-glucan using fractionated (1-3)-beta-D-glucan-sensitive component, factor G, eluted from the limulus lysate . Previously, we reported that the G test is a more sensitive method than the mannan detection assay for the serological diagnosis of Candida infection . In this study, we discuss beta-glucanemia in patients with pulmonary aspergillosis and cryptococcosis . The concentration of beta-glucan was less than 10 pg/ml in 9 of 10 cases of pulmonary cryptococcosis, except for one case receiving hemodialysis (16.5 pg/ml) . beta-Glucan increased in 3 cases of invasive pulmonary aspergillosis (27-937 pg/ml) . Galactomannan antigen was positive in all of those cases . In 8 cases of aspergilloma, which showed fungus ball on roentgenogram, the mean concentration of beta-glucan was 67.1 +/- 92.7 pg/ml . Two of 8 cases were positive for galactomannan antigen . One of three cases of PAIC (productive aspergilloma on the inner wall of a cavity) and one case of chronic necrotizing pulmonary aspergillosis showed slightly increased levels of beta-glucan and positive results of galactomannan antigen test. Antonie Van Leeuwenhoek, 1994, 65(1), 55 - 62 Yeast communities of the cactus Pilosocereus arrabidae and associated insects in the Sandy coastal plains of southeastern Brazil; Rosa CA et al.; The yeast communities from necrotic tissues, decaying flowers and fruits, and from larval feeding sites of the moth Sigelgaita sp . in the cactus Pilosocereus arrabidae were surveyed in three restinga ecosystems in Southeastern Brazil . Insects associated with these substrates were sampled to verify the vectoring of yeasts . The cactus Pilosocereus arrabidae was shown to have four different yeast communities associated with it . Necrotic stems had a diverse yeast community with the prevalent species Pichia barkeri, Candida sonorensis, Pichia cactophila, Geotrichum sp., Myxozyma mucilagina and Sporopachydermia sp . A, representing about 80% of the total isolates . Pichia sp . A and a Candida domercqii-like species represented more than 90% of the yeast isolates from decaying flowers . Fruits had a heterogeneous yeast community with typical fruit yeasts of the genus Kloeckera, basidiomicetous anamorphs of the genus Cryptococcus, the black yeast Aureobasidium pullulans, Pichia sp . A, a Candida domercqii-like species, and some cactophilic yeasts, especially Clavispora opuntiae . The feeding site of Sigelgaita sp . larvae had Clavispora opuntiae as the prevalent species . Insect vectors are suggested as one the most important factors influencing the composition of these yeast communities. Mycopathologia, 1994 Jan, 125(1), 7 - 17 In vivo depletion of murine CD8 positive T cells impairs survival during infection with a highly virulent strain of Cryptococcus neoformans; Mody CH et al.; Cell-mediated immunity plays an important but incompletely understood role in host defense against Cryptococcus neoformans . Because of their multiple capacities as cytokine-secreting cells, cytotoxic cells, and antigen-specific suppressor cells, CD8 positive T lymphocytes could potentially either enhance or impair host defense against C . neoformans . To determine whether CD8 T cells enhance or inhibit host defence during an infection with a highly virulent strain of C . neoformans, we examined the effect of in vivo CD8 cell depletion on survival and on the number of organisms in mice infected by either the intratracheal or intravenous routes . Adequacy of depletion was confirmed both phenotypically and functionally . Regardless of the route of infection, we found that survival of mice depleted of CD8 T cells was significantly reduced compared to undepleted mice . Surprisingly, however, CD8 depletion did not alter organism burden measured by quantitative CFU assay in mice infected by either route . These data demonstrate that CD8 positive T cells participate in the immune response to a highly virulent strain of C . neoformans . By contrast to minimally virulent isolates that do not cause a life threatening infection, the immune response to a highly virulent isolate does not alter the burden of organisms, but does enhance host defense as it is necessary for the optimal survival of infected mice. Bull Soc Pathol Exot, 1994, 87(1), 41 - 4 {Tests for an early detection of pulmonary cryptococcosis by sputum culture}; Mukamurangwa P et al.; Cryptococcosis is a serious opportunistic infection occurring in acquired immunodeficiency syndrome (AIDS) patients . As the number of infected patients with the human immunodeficiency virus (HIV) in Central Africa and especially in Rwanda increases, the prevalence of cryptococcosis can also be expected to rise . An earlier diagnosis and treatment will improve the prognosis of cryptococcosis . As it is widely accepted that the lungs are the portal of entry for the yeast, 270 sputum samples coming from 230 patients attending the Centre Hospitalier de Kigali (CHK)--Rwanda for lung diseases, were investigated . Cr . neoformans var neoformans was cultured from 8 samples coming from 5 out of 230 patients . A retrospective review showed that 4 out of 5 patients were infected with HIV, a predisposing factor for cryptococcosis. J Med Vet Mycol, 1994, 32(4), 315 - 8 Cryptococcus neoformans vertebral osteomyelitis; Gurevitz O et al.; A 67-year-old previously healthy woman presented with low back pain of 2 months duration and daily fever of 39 degrees C for 3 weeks . CT scan showed a lytic lesion in the third lumbar vertebra and a small right lower lobe lung infiltrate with mediastinal lymphadenopathy . Culture of material obtained from open biopsy of the vertebra grew Cryptococcus neoformans var . neoformans, which was also demonstrated on histology . Cryptococcal antigen was detected in the patient's serum . Treatment with amphotericin B (1000 mg total dose) and oral 5-fluorocytosine, resulted in complete recovery and resolution of the chest X-ray findings with a follow-up of 2 years . Since this case, as well as most of the previously described cases of cryptococcal osteomyelitis, were in normal hosts, cryptococcal osteomyelitis should be considered in the differential diagnosis even in a normal host, and therefore, prior to possible invasive diagnostic procedures, cryptococcal antigen in the serum should be determined. J Med Vet Mycol, 1994, 32(4), 303 - 13 Melanin-deficient mutants of Cryptococcus neoformans; Torres-Guererro H et al.; Cryptococcus neoformans is a significant fungal pathogen in immunocompromised patients . The ability of C . neoformans to produce melanin has been correlated with virulence . The role of melanin in promoting virulence is unclear, although an anti-oxidant function has been suggested . To begin to define the genetic mechanisms responsible for melanin production in C . neoformans, we describe the isolation of seven melanin-deficient mutant classes . Some of the mutants can be suppressed by addition of Cu2+ to media, suggesting that the phenoloxidase of C . neoformans, like other fungal phenoloxidases, contains copper . Other mutants display a recessive sterile phenotype . A genetic and phenotypic characterisation of these mutants is presented. Mycoses, 1994 Jan-Feb, 37(1-2), 27 - 33 Comparison of in vitro antifungal activity of itraconazole and hydroxy-itraconazole by colorimetric MTT assay; Mikami Y et al.; The in vitro antifungal activities of itraconazole and its active hydroxyl metabolite, hydroxy-itraconazole (R 63372), against Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans were compared by visual assessment of growth as well as by colorimetric MTT {3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide} assay using microtitre plates containing four different media . Minimum inhibitory concentration (MIC) end points determined by the colorimetric MTT assay correlated well with those obtained by visual assay . The two drugs showed different MIC values depending on the medium used . The activity of itraconazole was equal to or greater than the activity of hydroxy-itraconazole against most of the fungi tested . Both drugs showed lower MIC values against A . fumigatus and Cr . neoformans in brain heart infusion broth (BHI) medium than in yeast nitrogen base (YNBG) medium, Sabouraud glucose broth (SAB) or "synthetic amino acid medium, fungal" (SAAMF) . However, the MIC end point of these drugs against C . albicans in BHI and SAB media was difficult to determine visually as well as by MTT assay . In C . albicans, the MTT assay method using SAAMF and YNBG media is recommended for the determination of MICs. Mycoses, 1994 Jan-Feb, 37(1-2), 23 - 6 Incidence of cryptococcosis in and around Chandigarh, India, during the period 1982-91; Chander J et al.; The incidence of cryptococcosis was evaluated in and around Chandigarh, India over a period of 10 years (1982-91) . Different species of Cryptococcus were isolated from 38 patients . Cryptococcus neoformans was the predominant isolate (26 = 68%) followed by Cr . albidus (2), Cr . laurentii (1) and not precisely identified Cryptococcus species (9 = 24%) . Serotyping of the 18 isolates of Cr . neoformans revealed that 13 (72%) were serotype A, two (11%) were serotype AD and three (17%) were serotype B (Cr . neoformans var . gattii) . Cryptococcus species were found to produce infection in 24 patients and were possibly transient colonizers in another 14 patients . In addition, in 11 patients no Cryptococcus species was isolated from any site but the latex agglutination test for antigen (Crypto-LA) was positive in serum and/or cerebrospinal fluid . Response to various antifungal drugs was also studied in these patients. J Leukoc Biol, 1994 Jan, 55(1), 35 - 42 The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection; Huffnagle GB et al.; Moderately virulent strains of Cryptococcus neoformans, inoculated via the trachea, cause a pulmonary infection in BALB/c mice that was gradually resolved by T lymphocyte-dependent mechanisms . The current studies, using monoclonal antibodies to deplete T cell subsets, demonstrated that CD4+ and CD8+ T cells combined to mediate a prominent pulmonary inflammatory infiltrate that included lymphocytes, macrophages, neutrophils, and eosinophils . The inflammatory response peaked 2 weeks after infection and coincided with the beginning of gradual pulmonary clearance of the infection . CD4/CD8 double deficiency (4-8-) markedly reduced the influx of all cells into the lungs . A CD4 deficiency had a more profound effect on the total number of inflammatory cells recruited to the lungs than a CD8 deficiency . Depletion of either CD8+ or CD4+ T cells significantly decreased pulmonary macrophages and neutrophils, but only a CD4 deficiency prevented the influx of eosinophils . Recruitment of CD8+ T cells occurred independently of CD4+ T cells, but CD4+ T cell recruitment to the lungs was significantly reduced in CD8-deficient mice . Mitogen-stimulated infiltrating lung lymphocytes from infected 4+8+ mice secreted both T helper cell type 1 (Th1) {interferon-gamma (IFN-gamma) and interleukin-2 (IL-2)} and Th2 (IL-4, IL-5, and IL-10) cytokines . CD4 deficiency resulted in loss of T cells secreting IL-4, IL-5, and IL-10 . However, residual CD8+ T cells still secreted IL-2 and IFN-gamma . Lung T cells from CD8-deficient mice secreted similar levels of IL-4, IL-5, and IL-10 on a per lung basis compared with 4+8+ mice despite decreased numbers of CD4+ T cells, but secreted reduced levels of IFN-gamma . These experiments indicate that (1) CD4+ T cells play a dominant role in recruiting macrophages and granulocytes to the lung and (2) CD8+ T cells also mediate cellular recruitment, increase the magnitude of CD4+ T cell numbers in the infiltrate, and contribute to the local secretion of IFN-gamma . Thus, these studies demonstrate that CD8+ T cells can independently mediate an inflammatory response to a large, particulate, extracellular antigen, a role heretofore attributed almost solely to CD4+ T cells. Microbiol Immunol, 1994, 38(11), 851 - 6 Influence of molecular sizes of Cryptococcus neoformans capsular polysaccharide on phagocytosis; Yasuoka A et al.; The role of capsular polysaccharides (CPS) of Cryptococcus neoformans in phagocytosis by murine alveolar macrophages was investigated in four strains of C . neoformans serotype A, YC-11, YC-5, YC-27 and YC-13 . Phagocytosis rates increased markedly after adding 10% mouse serum, compared to fetal calf serum . The reverse relation between capsular thickness of C . neoformans and phagocytosis by alveolar macrophages was observed except in YC-27, which had thin capsules and high virulence . The phagocytosis rate in mice serum was 17.3% in YC-11 (capsule thickness 2.8-3.5 microns), 39.8% in YC-5 (capsule size 0.8-1.5 microns), 20.3% in YC-27 (capsule size 0.6-1.1 microns), and 62.8% in YC-13 (capsule not detected microscopically) . The CPS of YC-11, YC-5, and YC-27 analyzed by gel-filtration using CL-2B showed high molecular fractions near the void volume . However, the CPS of YC-13 showed only low molecular fractions . The widely eluted CPS of YC-11 was separated into 3 fractions and each fraction was added in the phagocytosis assay of YC-13 . Phagocytosis was markedly suppressed particularly by the addition of a higher molecular fraction . These results suggest that phagocytosis of C . neoformans by alveolar macrophages is influenced by the molecular sizes of the CPS. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi, 1994, 12(3), 188 - 91 {Experimental and clinical study on pneumocystosis . III . Development and characterization of monoclonal antibody against Pneumocystis carinii}; Mei Q et al.; BALB/c mice were repeatedly inoculated subcutaneously with purified rat source Pneumocystis carinii (P.c.) cysts . Six weeks later, the spleen cells were fused with NS1 myeloma cells, and a mouse hybridoma producing monoclonal antibody against P.c . was established and cloned, which was named as 4D7 McAb . Its mean of chromosome was 82 . The 4D7 McAb was shown to be IgG1 subclass . It reacted mainly with 54 kDa polypeptide of P.c . in EITB . 4D7 McAb could clearly recognize P.c . by immunohistochemical staining in the specimens from confirmed Pneumocystis carinii pneumonia (PCP) patients, and the sensitivity and specificity were both 100% for diagnosis of PCP (11/11) . No cross-reaction of 4D7 McAb was found with Pneumococcus, Candida albicans and Cryptococcus neoformans, as well as all examined normal human tissues. Biotherapy, 1994, 7(3-4), 195 - 210 Cytokines in the treatment of fungal infections; Kullberg BJ et al.; The incidence of invasive fungal infections in the immunocompromized host has increased during the past decade . Even the recently developed antifungal drugs are unable to cure these infections in patients with severely impaired host defense mechanisms . Cytokines have great potential to augment host resistance and as adjunctive therapy of invasive mycoses . We discuss the mechanisms of host defense against invasive candidiasis, aspergillosis, and cryptococcosis, and review the use of cytokines and growth factors in this setting . Interleukin-1 has been shown effective in an animal model of disseminated candidiasis, even during severe granulocytopenia . Interferon-gamma has been very effective as a modulator of resistance against a variety of fungal infections in vitro . The effect of interferon-gamma against disseminated candidiasis has been demonstrated in a mouse model . Activation of neutrophils is the main mechanism by which interferon-gamma enhances the elimination of Candida, and consequently the agent is not effective in severely granulocytopenic animals . Data on the role of colony-stimulating factors against fungal pathogens are accumulating, and trials with these agents for hematologic patients with invasive fungal infections are now being performed. AIDS, 1994, 8 Suppl 2, S35 - 43 Late manifestations of HIV in Asia and the Pacific; Clezy K et al.; PIP: Late-stage HIV infection is characterized by profound immunodeficiency with a progressive and irreversible decline in the CD4 count, functional impairment of cellular and humoral immunity, and evidence of increased viral replication, with the appearance of p24 antigenemia and increasing levels of beta(2)-microglobulin and neopterin . These changes are associated with increased susceptibility to many infections, the emergence of malignancies, and neurological complications due to the direct infection of neural tissue with HIV . In Australia, opportunistic infections and malignancies account for 75% and 18% of AIDS diagnoses, respectively . Opportunistic infections and neurological involvement usually occur late in the illness and may be associated with disturbances of function of each part of the neuraxis . The detailed clinical nature of the involvement has been described in several recent reviews and is probably not different in the Asia-Pacific region . The most common opportunistic infections in Australia are Pneumocystis carinii pneumonia (PCP), esophageal candidiasis, toxoplasmosis, CMV infection, atypical mycobacteriosis, and cryptococcal meningitis . There are few data from Asian countries, but it seems that the most common opportunistic infections are tuberculosis, PCP, systemic Penicillium marneffei infection, and cryptococcal meningitis . There is little information from Asia on neurological conditions . Tuberculosis is probably the most significant threat to public health in Asia and the Pacific . Its management and prevention require ongoing planning and resources . To that end, a collaborative effort is called for to help resource-poor countries . Mycobacterial, fungal, viral, and protozoal infections are discussed, along with consideration of neurological complications, malignant disease, and late manifestations of HIV infection in children . Scand J Infect Dis, 1994, 26(5), 623 - 6 Cellulitis as first clinical presentation of disseminated cryptococcosis in renal transplant recipients; Horrevorts AM et al.; Two renal transplant recipients with cellulitis due to Cryptococcus neoformans are described . The patients were treated empirically for a presumed bacterial erysipelas, but without response . Examination of skin biopsies revealed C . neoformans as the causative organism . In both patients the cellulitis was the presenting clinical manifestation of disseminated cryptococcosis . Therapy with antifungal agents was successful . Disseminated cryptococcal disease occurs mainly in immunocompromised patients . When left untreated, it nearly always has a fatal course . Early diagnosis and appropriate therapy are therefore essential. Mycoses, 1994, 37 Suppl 1, 34 - 42 {Pathogenesis, immunobiology and epidemiology of cryptococcosis}; Muller J; Cryptococcus neoformans is taken up by the human host via the respiratory tract . The polysaccharide capsule is regarded as the pathogenetic principle inhibiting phagocytosis of the fungus by cells of the unspecific host defense . Unspecific opsonization of Cr . n . by early phase proteins causes a rapid and successful elimination in the non-compromised host . In case of non-elimination the presence of Cr . n . capsule antigen in excess results in a downregulation of antibody formation thereby inhibiting specific opsonization . Furthermore the blockade of specific T cells and cytotoxic cells by means of free antigen and/or immunocomplexes causes a downregulation of the cellular immunity: Cr . n . antigens of different character induce T suppressor cells inhibiting cellular immunity via a cascade of effector cells and soluble factors . The AIDS patient enters cryptococcosis in a state comparable to a Cr . n.-infected non-AIDS patient whose cellular immunity is already downregulated by this mycosis itself . Both phenomena--the mycosis-induced downregulation of cellular immunity as well as the AIDS-specific lack of CD4 helper cells and its consequences--act, therefore, synergistically in the same pathogenetic direction . This explains the fulminant development and sequel of cryptococcosis typical with AIDS patients . Most probably each exposition of an AIDS patient to Cr . n . results in clinically manifest cryptococcosis . The frequence of cryptococcosis in AIDS is, therefore, reflecting the general exposure of humans to Cr . n . in a given region . Cryptococcosis in AIDS is at least about 1000x more frequent than cryptococcosis in non-AIDS individuals.(ABSTRACT TRUNCATED AT 250 WORDS) Mycoses, 1994, 37 Suppl 1, 28 - 33 {One hundred years of cryptococcosis . Medical mycology in the 19th century in Greifswald}; Knoke M et al.; Not later than 1842 medico-mycological investigations began at Greifswald in Germany following the appointment of Wilhelm Baum (1799-1883) to the chair of surgery at the university . This is indicated by some theses as well as by the discovery of the contagious characteristics of pityriasis versicolor by Carl Ferdinand Eichstedt (1816-1892) who found a fungus as the cause (1846), which was named Microsporon furfur later (C . Robin 1853) . In 1868 the physician (Karl) Friedrich Mosler (1831-1911) published clinical-mycological studies and investigations on animal feeding with yeasts . Some time later (1870) Friedrich Grohe (1830-1886) and his assistants Alwin R . A . Block (1843-?) and M . R . Roth of the Pathological Institute described results of transmission-studies with "Aspergillus glaucus, Penicillium glaucum and yeast" . The successor to the chair, Paul Grawitz (1850-1932), also published results of his own mycological investigations . Finally, on 7 July, 1894, during the evening lecture of the Greifswald Medical Society Abraham Buschke (1868-1943) from the Hospital of Surgery gave a talk "on a peculiar disease caused by coccidia" followed by the talk of pathologist Otto Busse (1867-1922) on a "demonstration of a pathogenic coccidia species" . Busse's subsequent publications are the first proper descriptions of cryptococcosis (1894 f) . Nevertheless, Cryptococcus neoformans has been named in connection with F . Sanfelice, whose results were published later (1895). Langenbecks Arch Chir, 1994, 379(6), 372 - 5 Fungal infections in liver transplant recipients; Grauhan O et al.; A retrospective analysis of 462 consecutive orthotopic liver transplantations was undertaken to evaluate incidence, risk factors, clinical course, and outcome of fungal infections . Infections involving Aspergillus (6 cases), Candida (5 cases), Mucor (1 case), and Cryptococcus (1 case) were observed in 2.8% (13/462) of our patients . Twelve of the 13 episodes developed during the first 2 postoperative months . None of the potential risk factors for fungal infections described by other authors (i.e., age, rejection treatment, dialysis, mechanical ventilation, graft failure, long operation time, second transplant, serious non-fungal infection) correlated significantly with the episodes in our patients . However, in patients who exhibited three or more of these potential risk factors the incidence of fungal infections was elevated (P < 0.001) . Six of seven exogenous infections (Aspergillus, Mucor) began before July 1991 when our department moved from Charlottenburg to Wedding, thus indicating that the incidence of these infections is highly influenced by exposure (P = 0.01) . Exposure prophylaxis should therefore by meticulously followed, particularly when severely compromised patients are involved, in order to prevent exogenous infections (i.e., Aspergillus/Mucor) . Infections involving such patients are combined with a very high mortality (57%) . We observed Candida infection as a pathological overgrowth of physiological oropharynx flora into the esophagus and/or trachea in five patients . In each case treatment led to full recovery. J Med Vet Mycol, 1994, 32(5), 401 - 4 Strains of Cryptococcus neoformans with defined capsular phenotypes; Jacobson ES et al.; The polysaccharide capsule is a virulence factor in the opportunistic yeast pathogen, Cryptococcus neoformans . We describe a collection of strains which were isolated or constructed to exhibit defined capsular phenotypes . The collection includes strains with wild-type, acapsular and hypercapsular traits. J Med Vet Mycol, 1994, 32(5), 395 - 9 Systemic fungal infections in Thailand; Imwidthaya P; Between January 1988 and December 1993, 254 cases of systemic mycoses were recorded in Thailand . Between 1988 and 1991, the common mycoses were aspergillosis, candidosis and cryptococcosis . In 1992, cryptococcosis increased to 30 cases with 27 being AIDS related . In 1993, cryptococcosis increased dramatically to 57 cases with 49 AIDS related . Eight cases of penicillosis marneffei occurred in AIDS patients in 1993 . Skin manifestations of penicillosis marneffei and histoplasmosis in AIDS usually manifested as molluscum contagiosum-like papulonecrotic lesions . Clinical signs and symptoms could not be differentiated from each other. Mycoses, 1994, 37 Suppl 2, 8 - 19 {Aspects in the diagnosis of deep-seated opportunistic mycoses}; Fegeler W; Possibilities for the mycological, mycoserological and clinical diagnostics of deep-seated opportunistic mycoses--cryptococcosis, aspergillosis and candidosis--are shown . Improvements of the diagnostics and interpretation by consideration of pathogenesis and clinical situation are discussed. Mycoses, 1994, 37 Suppl 2, 56 - 63 {Therapy of candidiasis and cryptococcosis in AIDS}; Just-Nubling G; Fungal infections figures large in HIV-infected patients . Candida infections of the mucous membranes belong to the main manifestations of immunodeficiency in HIV infection . For therapy and prophylaxis of oropharyngeal candidosis mainly systemically acting azoles as ketoconazole, fluconazole and itraconazole are applied; antimycotics to be administered topically regularly fail to act in patients with progressing disease . Ketoconazole tablets were used with good success in previous years of the AIDS epidemics . Application of ketoconazole in liquid formulation led to a significant increase in efficacy . Subsequently fluconazole proved to be a triazole with evidently better pharmacological properties leading to good clinical efficacy . Presently it represents the drug of first choice in acute and maintenance therapy of recurrent oropharyngeal and oesopharyngeal candidosis . In the case of therapy failure with fluconazole the administration of itraconazole in liquid cyclodextrine formulation can replace or at least delay the administration of amphotericin B plus flucytosine, a therapy rich in toxic side effects . The standard therapy of disseminated cryptococcosis--particularly of cerebral manifestation--is still the administration of amphotericin B combined with flucytosine . Alternative drugs are represented by fluconazole and itraconazole . However, an azole monotherapy seems to be legitimate only in primary cryptococcosis of the lungs or in early stages of secondary extrapulmonary infection . Cryptococcal meningitis requires an intense initial therapy . New therapy strategies were developed combining azoles with standard antimycotic drugs . The value of amphotericin B in liposomal or lipid complex formulations is still undetermined due to the up to now low number of AIDS patients treated.(ABSTRACT TRUNCATED AT 250 WORDS) Mycoses, 1994, 37 Suppl 2, 27 - 33 {Pharmacokinetics of itraconazole}; Cauwenbergh G; Itraconazole is a lipophilic triazole antifungal with a broad spectrum of activity . Most of the important fungal pathogens respond to itraconazole concentrations of 100 ng/ml . Therefore, itraconazole is suitable for treatment of a variety of systemic mycoses, as aspergillosis, cryptococcosis, candidosis as well as non-European endemic mycoses . The lipophilicity of the molecule is the reason for a pronounced tissue affinity meaning that the tissue levels of the drug usually are substantially higher than the corresponding plasma levels . This fact has to be kept in mind when plasma measurements are being used to decide a therapeutic approach for a systemic fungal infection . In contrast to the skin, internal organs will not show a long term retention of itraconazole in the tissues . This means that for systemic mycoses the therapy needs to be continued until clinical and mycological cure is obtained . Reduced itraconazole absorption may occur in a minority of patients because of underlying chemotherapy or dramatic changes in stomach pH . This is occasionally seen in patients with allogeneic bone marrow transplants and end-stage AIDS patients . Use of antacida and H2-antagonists somewhat reduces the absorption of itraconazole, however, often not in a clinically meaningful way . Itraconazole increases the levels of cyclosporin A . Itraconazole levels are decreased by rifampicin, phenytoin and phenobarbital . Caution is required in patients on concomitant anticoagulants. Mycoses, 1994, 37 Suppl 2, 1 - 7 {Epidemiology of deep-seated, domestic mycoses}; Muller J; The opportunistic character of deep-seated mycoses depends on granulocyte-based defense in candidosis and aspergillosis . Therefore, haematological, patients represent the group of highest risk . Mucocutaneous candidosis is controlled by macrophages . Cryptococcus neoformans forces its way into the human host via causing an imbalance in the CD8-T-cell suppressor system . An aggravating synergism exists between Cryptococcus invasion and HIV-infection which explains the severe course of cryptococcosis in AIDS patients . The following pathways of transmission are observed in opportunistic mycoses: In aspergillosis and cryptococcosis humans are infected by inhalation of fungal propagules and primary settlement of the pathogens in the lungs, a site from which dissemination may occur . Exposure to Aspergillus conidiospores is ubiquitous and can be remarkably intensified by construction activities . Exposure to Cr . neoformans is geographically highly variable; not all humans are exposed . Candidosis emerges from the commensal reservoir of the human gastrointestinal tract, caused by translocation of the pathogens from the GI tract into the blood-lymph circulation or by anal/oral or oral-oral infection respectively . The incidence of deep-seated mycoses in the northern hemisphere is estimated to be 600 mycosis situations per million population per year . The estimate for Germany amounts to 50,000 mycoses patients per year, i.e . 45,000 candidosis and 5,000 aspergillosis situations as well as 100 each of cryptococcal and other mycotic diseases . Beyond that the number of AIDS-patients with cryptococcosis in Germany amounts to about 200 cases. Dev Neurosci, 1994, 16(3-4), 152 - 61 Reactive nitrogen intermediates in human neuropathology: an overview; Brosnan CF et al.; Nitric oxide (NO) is a recently recognized messenger molecule that has been shown to possess pleiotropic properties, including vasodilation, neurotransmission, cytotoxicity and antimicrobial activity . Constitutive and inducible forms of NO synthase (NOS) have been identified . Activation of cNOS releases relatively low levels of NO for short periods of time whereas induction of iNOS releases high levels of NO for extended periods of time . In rodents, iNOS is predominantly found in cells of the monocyte/macrophage series, including microglia, where it is induced by a combination of bacterial products and cytokines . cNOS and iNOS have also been reported in rodent astrocytes . Activation of iNOS in the CNS could be toxic to many different cell types, including neurons and oligodendrocytes . iNOS, however, has been difficult to demonstrate in human peripheral blood cells, suggesting that the regulation of expression of this enzyme in humans is different from that found in rodents . In this overview, we show that in human glial cells cultured in vitro, astrocytes, but not microglia, can be induced by cytokines to express NO-like activity . Bacterial products are without effect, but a combination of IL-1 and TNF alpha or IFN gamma is a potent stimulus . NO production by astrocytes inhibits Cryptococcus neoformans growth in vitro . In vivo, we show in acute multiple sclerosis lesions, intense NADPH-diaphorase activity is present in hypertrophic astrocytes in the lesion center and at the lesion edge, whereas microglia are nonreactive . Increased NADPH-diaphorase activity colocalizes with immunoreactivity for IL-1 and TNF . These results suggests that the induction of reactive nitrogen intermediates in humans differs from that found in rodents, and supports the conclusion that hypertrophic astrocytes are the major source of NO-like activity in the inflamed CNS. J Med Vet Mycol, 1994, 32(5), 361 - 72 Comparisons between in vitro glial cell adherence and internalization of non-encapsulated and encapsulated strains of Cryptococcus neoformans; Merkel GJ et al.; The adherence of non-encapsulated and encapsulated strains of Cryptococcus neoformans to rat glial cells in culture was compared . Like the encapsulated strain, the adherence of the unencapsulated strain was affected by the yeast culture age and growth temperature . Yeasts grown to late stationary phase at 37 degrees C were the most adherent . Neither encapsulated nor non-encapsulated strains adhered to glial monolayers when the experiments were conducted at 5 degrees C, indicating that metabolically active mammalian cells were required for yeast adherence . Additionally, the non-encapsulated strain was consistently three times more adherent than the encapsulated strain, suggesting that the non-encapsulated strain either had more adhesins or more adhesins were exposed . Electron microscope studies indicated that both strains were internalized by glial cells, an event previously not reported for this mammalian cell type . The same carbohydrates (N-acetyl-D-glucosamine, sucrose and inositol) that inhibited adherence of the encapsulated strain the most, also inhibited adherence of the non-encapsulated strain, again indicating similar adhesin mechanisms . Both encapsulated and non-encapsulated strains were made non-adherent by treatment with pronase, papain, trypsin and amylase . Immobilized amylase appeared to remove an adhesin fragment that bound to glial cells and inhibited the adherence of intact cryptococci. J Med Vet Mycol, 1994, 32(3), 163 - 80 The 16S-like, 5.8S and 23S-like rRNAs of the two varieties of Cryptococcus neoformans: sequence, secondary structure, phylogenetic analysis and restriction fragment polymorphisms; Fan M et al.; The nucleotide sequences of the 16S-like, 5.8S and 23S-like rDNAs from the two varieties of Cryptococcus neoformans, C . neoformans var . neoformans and C . neoformans var . gattii, were determined . The rRNA locus has the typical eukaryote organization of 16S-5.8S-23S with the 16S-like and 5.8S rRNA genes separated by a 124-nucleotide spacer and the 5.8S and 23S-like rRNA genes separated by a 187-nucleotide spacer in each strain . The C . neoformans var . neoformans and C . neoformans var . gattii 16S-like, 5.8S and 23S-like rRNAs are, respectively 1802, 158, and 3358 nucleotides in length and share > 99% nucleotide sequence identity, a finding which strongly supports the present taxonomic classification of two varieties within a species . Comparative structure analysis was used to construct secondary-structure models for the deduced 16S-like and 5.8S-23S-like rRNA sequences, which are similar to those of other fungal rRNAs . The C . neoformans 16S-like and 23S-like rRNA sequences were aligned with other eukaryote sequences based on secondary and higher-order structures predicted by comparative structure analysis for phylogenetic analysis . There was good correspondence between the 16S-like and 23S-like derived phylogenetic trees . The closest known fungal relative is Trichosporon beigelii . Southern blot analysis revealed one C . neoformans strain with two types of DNA repeats coding for rRNA which differed in size by about 1000 bp . Restriction fragment length polymorphisms in the rDNA locus provide useful markers for the study of epidemiology and pathogenesis of C . neoformans infections. Am J Ophthalmol, 1993 Dec 15, 116(6), 721 - 7 Ophthalmic manifestations of infections with Cryptococcus neoformans in patients with the acquired immunodeficiency syndrome; Kestelyn P et al.; The present study was undertaken to determine the nature and the prevalence of ophthalmic manifestations of infections with Cryptococcus neoformans in human immunodeficiency virus seropositive patients and to analyze whether the presence or absence of ocular signs is associated with improved survival . Eighty human immunodeficiency virus seropositive patients with cryptococcal infection were enrolled . We observed papilledema in 26 of the 80 patients (32.5%) . Visual loss and abducens nerve palsy occurred in seven patients (9%) . Only two patients (2.5%) had optic atrophy . Visual loss caused by optic nerve involvement was less frequent among the 62 patients treated with oral conazoles exclusively than among the 18 patients who had received amphotericin B or a combination of amphotericin B and conazoles . Actual invasion of the intraocular structures with Cryptococcus neoformans was an uncommon complication in our series . In addition to the ocular manifestations attributable to cryptococcal disease, human immunodeficiency virus-related retinopathy was present in nearly half of the patients . Cytomegalovirus retinitis was diagnosed in four patients (5%) . The 26 patients (32.5%) with papilledema had a median survival of 182 days vs 160 days for the patients without papilledema . The median survival for 18 patients (22.5%) with cotton-wool spots was 102 days vs 186 days for those without cotton-wool spots . The differences between these subgroups were not statistically significant. Semin Dermatol, 1993 Dec, 12(4), 310 - 4 Histoplasmosis; Hay RJ; Histoplasmosis is an infection caused by the dimorphic fungus, Histoplasma capsulatum . The initial site of entry is usually the lung, but dissemination to skin occurs in some patients, particularly those with human immunodeficiency virus (HIV) infection in whom it is part of a widespread infection . The organisms have to be distinguished from other yeasts in skin such as Cryptococcus neoformans and small forms of Blastomyces dermatitidis. Vnitr Lek, 1993 Dec, 39(12), 1192 - 8 {The most common pathogens in opportunistic mycoses and their clinical manifestations}; Haber J et al.; The most frequent pathogens of opportunistic mycotic infections are Candidae . The clinical manifestation of infection is very varied . With regard