Semin Neurol, 2002 Mar, 22(1), 9 - 15 What I have learned about infectious diseases with my sleeves rolled up; Roos KL; The questions most often asked of my residents and myself are the following: (1) How do you interpret the cerebrospinal fluid white blood cell count and polymerase chain reaction results when the lumbar puncture has been traumatic? (2) Does the older adult with a serum sample that tests positive by the Venereal Disease Research Laboratory test need spinal fluid analysis for neurosyphilis, and which of those syphilis tests can become nonreactive even though the patient is never treated? (3) Do you give steroids to patients with bacterial meningitis? (4) What do you do for the patient with cryptococcal meningitis who develops a spastic gait? (5) Are all cases of transverse myelitis "idiopathic"? and (6) When does the patient who has had a stroke need spinal fluid analysis to rule out an infectious etiology? This is how we answer these questions. Rev Soc Bras Med Trop, 2002 Jul-Aug, 35(4), 347 - 50 {Seroepidemiological survey for infections by fungi causing systemic mycoses in the Xacriabá Indian Reserve, Minas Gerais State, Brazil}; Martinez R et al.; Xacriaba Indian Reserve is situated in the north of Minas Gerais State, Brazil, near the municipality of Manga and Sao Francisco River . The Indian population is miscegenated with caucasian and negroid people and have farming activities . Blood samples were collected from 180 inhabitants of the reserve (85 men and 95 women), 15 to 84 years old . Serum antibodies against antigens of Paracoccidioides brasiliensis, Histoplasma capsulatum, Cryptococcus neoformans, and Candida albicans were tested for by counterimmunoelectrophoresis method . Seropositivity was verified in 5%, 3.9%, 4.2%, and 6.7%, respectively of the 180 samples . Those seropositive for antigens of P . brasiliensis and H . capsulatum were predominantly women and had lower age and more elevated mean titers of antibodies than individuals whose sera reacted with antigens of C . neoformans and C . albicans . The results suggest the occurrence of paracoccidioidomycosis-infection and histoplasmosis-infection in the Xacriaba Indian Reserve, particularly in the first decades of life of the inhabitants. Pharmazie, 2002 Jul, 57(7), 491 - 3 Biologically active steroidal glycosides from Tribulus terrestris; Bedir E et al.; The steroidal saponin constituents obtained from Tribulus terrestris were tested for their antimicrobial and cytotoxic effects . The spirostanol-based steroidal saponins 1-3 exhibited remarkable activity against fungal organisms (Candida albicans and Cryptococcus neoformans) and cancer cell lines {human malignant melanoma (SK-MEL), human oral epidermoid carcinoma (KB), human breast ductal carcinoma (BT-549), and human ovary carcinoma (SK-OV-3)}, while none of the compounds possessing the furostanol framework 4-7 showed activity . The most active spirostanol glycoside, compound 3 exhibited a broad range of anticancer activity against cell lines, SK-MEL, KB, BT-549 and SK-OV-3 at IC50s of 6.0, 7.0, 6.0 and 8.2 micrograms/ml, respectively, while compounds 1 and 2 showed selective cytotoxicity against SK-MEL at 6.7 and 9.1 micrograms/ml, respectively . The minimum inhibitory concentrations (MIC) in antifungal bioassay for compounds 1-3 varied from 1.5 to 6.2 micrograms/ml, which prompted to conclude certain structural features are required for these bioactivities. Curr Opin Microbiol, 2002 Aug, 5(4), 386 - 91 Induced humoral immunity and vaccination against major human fungal pathogens; Casadevall A et al.; Protection against fungal pathogens can theoretically be elicited by vaccines that stimulate humoral or cellular immunity, or both . There is conclusive evidence that humoral immunity can modify the course of infection against certain pathogenic fungi such as Candida albicans and Cryptococcus neoformans . However, for other fungi, such as Aspergillus fumigatus, the notion that humoral immunity contributes to host defence is unproven . Attempts to evaluate the potential efficacy of humoral immunity using immune sera are often inconclusive, whereas consistent results can be obtained with monoclonal antibodies . Protective monoclonal antibodies can be used to identify antigens that induce useful humoral responses. J Assoc Physicians India, 1998 Jul, 46(7), 617 - 9 Cryptococcal meningitis in immunocompetent patients; Sanchetee P; Five cases of cryptococcal meningitis (CM) in immunocompetent patients who were initially diagnosed as either tuberculous meningitis or partially treated pyogenic meningitis are presented . There were 3 male and 2 female patients in the age range of 21 to 42 years . These patients presented as subacute meningitis . Additional features were visual impairment (4 cases), papilloedema (3 cases), sixth cranial nerve palsy (3 cases) and ataxic hemiparesis (one case) . There was a mediastinal mass of fungal aetiology in one patient . While routine analysis of CSF showed a variable picture, it is the India ink preparation, test for cryptococcal antigen and culture for fungus which gave the diagnosis . These patients were treated with standard antifungal therapy . While one patient died and one patient recovered completely, three other patients were left with permanent visual impairment . It is concluded that CM is uncommon but an important cause of non-acute meningitis and should be included in the list of causes of preventable blindness. J Vet Diagn Invest, 2002 Jul, 14(4), 337 - 9 Cryptococcosis in a llama (Lama glama); Bildfell RJ et al.; Cryptococcosis was diagnosed in a 17-year-old male llama that had been euthanatized following an acute onset of neurologic disease . Tissues affected included the brain, spinal cord, lung, and kidney . The character of the leukocytic response varied from minimal to pyogranulomatous . Cryptococcosis has not been previously reported in a llama, although the infection has been described in 2 other species of New World camelids . The pathogenesis of cryptococcosis is briefly reviewed. Expert Opin Investig Drugs, 2002 Aug, 11(8), 1117 - 25 Antifungals targeted to protein modification: focus on protein N-myristoyltransferase; Georgopapadakou NH; Invasive fungal infections have increased dramatically in recent years to become important causes of morbidity and mortality in hospitalised patients . Currently available antifungal drugs for such infections essentially have three molecular targets: 14 alpha demethylase (azoles), ergosterol (polyenes) and beta-1,3-glucan synthase (echinocandins) . The first is a fungistatic target vulnerable to resistance development; the second, while a fungicidal target, is not sufficiently different from the host to ensure high selectivity; the third, a fungistatic (Aspergillus) or fungicidal (Candida) target, has limited activity spectrum (gaps: Cryptococcus, emerging fungi) and potential host toxicity that might preclude dose escalation . Drugs aimed at totally new targets are thus needed to increase our chemotherapeutic options and to forestall, alone or in combination chemotherapy, the emergence of drug resistance . Protein N-myristoylation, the cotranslational transfer of the 14-carbon saturated fatty acid myristate from CoA to the amino-terminal glycine of several fungal proteins such as the ADP-ribosylation factor (ARF), presents such an attractive new target . The reaction, catalysed by myristoyl-CoA:protein N-myristoyltransferase (NMT), is essential for viability, is biochemically tractable and has proven potential for selectivity . In the past five years, a number of selective inhibitors of the fungal enzyme, some with potent, broad spectrum antifungal activity, have been reported: myristate analogues, myristoylpeptide derivatives, histidine analogues (peptidomimetics), aminobenzothiazoles, quinolines and benzofurans . A major development has been the publication of the crystal structure of Candida albicans and Saccharomyces cerevisiae NMTs, which has allowed virtual docking of inhibitors on the enzyme and refinement of structure-activity relationships of lead compounds. J Clin Microbiol, 2002 Aug, 40(8), 3098 - 9 First reported isolation of Cryptococcus neoformans var . gattii from a patient in Singapore; Taylor MB et al.; Cryptococcal meningitis has long been known to afflict immunocompetent patients in Singapore . We report the first identification of an isolate of Cryptococcus neoformans var . gattii from a Singaporean resident; this variety can cause invasive disease in the immunocompetent . Meningitis in a traveler returning from this area may be cryptococcal. Med Mycol, 2002 Jun, 40(3), 329 - 32 Determination of the pH of the Cryptococcus neoformans vacuole; Harrison TS et al.; We have previously demonstrated the antifungal activity of the weak bases chloroquine and quinacrine against Cryptococcus neoformans . Quinacrine, being fluorescent, was seen to be concentrated within a complex vacuolar structure within the cryptococcal cell . Here we determined the pH of this compartment using the pH-sensitive fluorescent dye, 5-(and 6-) carboxy-2',7'-dichlorofluorescein diacetate (carboxy-DCFDA) . Carboxy-DCFDA was concentrated within the cryptococcal vacuole, giving a pattern of fluorescence similar to that previously observed with quinacrine . For each experiment, a standard curve of fluorescence ratio against pH was generated using buffers of defined pH containing a mixture of ionophores and inhibitors to equilibrate vacuolar pH with that of the medium . The pH of the cryptococcal vacuole of five strains was calculated to range from 5.3 to 5.9 with a mean of 5.6 . This acidic pH is consistent with a model in which weak bases such as chloroquine and quinacrine are accumulated, by ion trapping within the fungal vacuole . Antifungal activity may result from the consequent disruption of pH-dependent processes as well as effects on other as yet undefined fungal targets. Med Mycol, 2002 Jun, 40(3), 323 - 8 Cryptococcus neoformans pulmonary granuloma formation is associated with matrix metalloproteinase-2 expression; Majka SM et al.; The aim of this study was to investigate matrix metalloproteinase (MMP) expression during the immune response to pulmonary Cryptococcus neoformans (Cne) infection . The immune response generated in C.B-17 and C57BL/6 mice to pulmonary Cne infection has previously been characterized as type 1 and type 2, respectively, differing in the cytokines produced and leukocytes recruited during infection, influencing the extent of Cne clearance from the lung . The focus of this study was to examine changes in expression of MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 in the lungs of Cne-infected mice during the two types (type 1 vs . type 2) of responses . C.B-17 mice that formed well-defined granulomas had elevated levels of pulmonary MMP-2 mRNA early during infection . C57BL/6 mice that had poorly defined cellular aggregates did not express detectable levels of pulmonary MMP-2 mRNA until later in the infection . Specific expression of MMP/TIMP was correlated with the type of immune response present, resolution of Cne infection and the resulting lung pathology. Med Mycol, 2002 Jun, 40(3), 273 - 82 Cryptococcus neoformans var . gattii in the koala (Phascolarctos cinereus): serological evidence for subclinical cryptococcosis; Krockenberger MB et al.; Cryptococcus neoformans var . gattii has been shown to have a strong association with eucalypts frequently used by koalas and, not surprisingly, it has been shown to colonize the nasal cavities of koalas . The progression from nasal colonization to tissue invasion is critical to understanding the pathogenesis of cryptococcosis in this species and provides a model for pathogenesis of cryptococcosis in other species . Cryptococcal antigenaemia was detected in twenty-eight healthy koalas from three different regions . This was interpreted as representing limited subclinical disease . One koala developed cryptococcal pneumonia 6 months after leaving the study, whereas another developed cryptococcal meningoencephalitis during the course of the study . Opportunistic necropsies on ten antigen-positive koalas resulted in discovery of small cryptococcal lesions in two (paranasal sinus and lung, respectively) . Our data suggest that cryptococcal antigenaemia occurs commonly in koalas, especially in areas with a high environmental presence of C n . var . gattii . Subclinical disease appears most likely to manifest as a small focal lesion in the respiratory tract . Possible outcomes include elimination by an effective immune response, quiescence with possibility of later re-activation or direct progression to overt disease . Symptomatic and subclinical cases showed differences in levels of antigenaemia . The data presented have significant implications for koalas in captivity. Med Mycol, 2002 Jun, 40(3), 263 - 72 Cryptococcus neoformans in the koala (Phascolarctos cinereus): colonization by C n . var . gattii and investigation of environmental sources; Krockenberger MB et al.; This study is the one in a series looking at the relationship among Cryptococcus neoformans var . gattii, koalas and the environment . The koala was used as a natural biological sampler in an attempt to understand the dynamics of C . neoformans var . gattii in Australian environments . Evidence of asymptomatic nasal and skin colonization for extended periods by large numbers of C . n . var . gattii was obtained and geographical factors assessed . The key finding was the ability of koalas to amplify numbers of C . n . var . gattii in certain environments . Koalas were not found to be obligatory for the survival of the organism in all environments . Geographical factors alone could not explain differing rates of nasal and skin colonization in koalas in different environments . A strong association between healthy koalas and C . n . var . gattii was confirmed and C n . var . gattii was isolated from novel sources, including the turpentine gum tree (Syncarpia glomulifera), tallowwood (Eucalyptus microcorys) and flooded gum (E . grandis) . It seems likely that as yet undiscovered environmental sources of C . n . var . gattii exist in eastern Australia . Further investigation of host, environmental and organism factors integral to the hostpathogen relationship will assist an understanding of the progression from colonization to tissue invasion and cryptococcosis in all species. Nippon Ishinkin Gakkai Zasshi, 2002, 43(3), 143 - 51 Histopathology of deep-seated fungal infections and detailed examination of granulomatous response against cryptococci in patients with acquired immunodeficiency syndrome; Shibuya K et al.; This understood without starting paper describes general histopathological features of deep-seated mycoses in patients with acquired immunodeficiency syndrome (AIDS) detailed histological examination on cryptococcal lesions with a consideration of morphological modification caused by treatment with highly active antiretroviral therapy (HAART) . In a histopathological review of 164 patients with total human immunodeficiency virus (HIV) infection, the microscopical appearance of esophageal candidiasis which was common in those with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue . The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida pneumonia . Nineteen patients including one treated with HAART had generalized cryptococcosis, representing the most common generalized fungal disease . The essential histologic features of the disease were yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components . This was different from those induced by both Candida and Aspergillus infections . Three histologic patterns were recognized in the pulmonary cryptococcal lesions, two of which could be graded with respect to the degree and type of inflammatory reaction . The first was a mild one consisting of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response . The second pattern involved massive cryptococcal infection, which might have been simply more extensive than that in the former . Capillary involvement of alveolar septa was an important common finding in the eighteen patients who had not been treated with HAART . The absence of T cells and decreasing function of antigen-presenting activity in histiocytes were confirmed by immunohistological examination . These findings suggest that the lungs of AIDS patients without HAART offer little resistance to bloodstream dissemination by Cryptococci . The third pattern demonstrated in the patient treated with HAART was characterized by the presence of CD4+ cells, greater response of histiocytes and multinucleated giant cell formation, and lack of massive capillary involvement. Nippon Ishinkin Gakkai Zasshi, 2002, 43(3), 137 - 41 {The role of natural killer T cells in host defense to cryptococcal infection--a bridge from innate to acquired immunity}; Kawakami K; Cryptococcosis is an opportunistic fungal infectious pathogen in immunocompromised patients with acquired immunodeficiency syndrome and hematological malignancies . The host defense to this pathogen is mediated mostly by cellular immunity . Th1-type cytokines including IFN-gamma, IL-12 and IL-18 play a pivotal role in this process . Recently, innate immunity mediated by NK, NKT and gammma-delta-T cells has garnered much attention from investigators . NKT cell has been identified as a particular cell population which recognizes glycolipids and participates in the development of tumor immunity and autoimmune diseases . In the present review, the accumulating knowledge on the roles of NKT cells in host defense to infectious pathogens are summarized with our own data on cryptococcal infection. Nippon Ishinkin Gakkai Zasshi, 2002, 43(3), 133 - 6 Receptor-mediated recognition of Cryptococcus neoformans; Levitz SM; Cryptococcus neoformans, a facultative intracellular pathogen of macrophages, is unique among medically important fungi in its possession of a polysaccharide capsule . Capsule represents the organism's major virulence factor . In the absence of opsonins, binding of encapsulated C . neoformans to macrophages is minimal . Following incubation in serum, C . neoformans potently activates complement, resulting in surface deposition of the third component of complement . Macrophages bind and phagocytose opsonized C . neoformans via three major complement receptors (CR) for C3 fragments, designated CD35 (CR1), CD11b/CD18 (CR3), and CD11c/CD18 (CR4) . Antibody in normal human serum generally lacks opsonic activity, although vaccination can elicit anticapsular antibodies that are opsonic . The major component of cryptococcal capsule, glucuronoxylomannan (GXM), is shed from the fungus and circulates in the blood and cerebrospinal fluid of patients with cryptococcosis . Cellular receptors defined for GXM include CD14, toll-like receptor-2, toll-like receptor-4, and CD18 . GXM binding to macrophage receptors triggers activation of nuclear factor-kB, but not mitogen-activated protein kinases . This results in no proinflammatory gene expression or release . C . neoformans also secretes mannoproteins, which are recognized by mannose receptors as well as by mannose-binding lectin, perhaps in conjunction with CD14 . Strategies directed at modulating how intact C . neoformans and its released components are recognized by phagocytes could lead to novel approaches to treating cryptococcosis QJM, 2002 Aug, 95(8), 511 - 8 Cryptococcaemia: clinical features and prognostic factors; Jean SS et al.; BACKGROUND: Limited data are available on the clinical significance of cryptococcaemia, which occurs in 10-30% of patients with cryptococcal diseases . AIM: To describe the clinical features of cryptococcaemia and identify its prognostic factors . STUDY DESIGN: Retrospective cohort study . METHODS: All adult patients with Cryptococcus neoformans isolated from blood culture at the National Taiwan University Hospital, Taipei, 1981-2001, were included . Demographic and clinical information was obtained from medical records . RESULTS: Fifty-two patients were diagnosed and treated for cryptococcaemia . Acquired immunodeficiency syndrome (24/52, 46%), immunosuppressive therapy (12/52, 23%) and decompensated liver cirrhosis (11/52, 21%) were the three major predisposing conditions . Forty-two patients (81%, n=52) had sepsis, including four patients with septic shock, when blood cultures were obtained . Of the 38 patients in whom lumbar puncture was done, cerebrospinal fluid culture showed meningeal involvement in 32 (84%) . The 30-day fatality rate was 37% . Liver cirrhosis, septic shock at presentation, an initial APACHE II score >/=20, age >/=60 years and female gender were associated with mortality under univariate analysis . Starting antifungal therapy within 48 h after blood culture was associated with improved survival . Under multivariate analysis, liver cirrhosis remained a strong independent predictor of mortality at 30 days after blood culture (HR 16.3, 95%CI 2.6-101.7, p=0.003) . DISCUSSION: Patients with cryptococcaemia have a high risk of mortality within 30 days . Sepsis and meningeal involvement are common . Those with liver cirrhosis have a particularly poor prognosis. BMC Microbiol . 2002 Jul 25;2(1):21. Identification of cultured isolates of clinically important yeast species using fluorescent fragment length analysis of the amplified internally transcribed rRNA spacer 2 region (ITS2); De Baere T et al.; BACKGROUND: The number of patients candidate to yeast infection has increased during the last years . Also the variety of species of clinical importance has increased . Correct species identification is often important for efficient therapy, but is based on phenotypic features and is sometimes time-consuming and depends largely on the expertise of technicians . Therefore, we evaluated the feasability of PCR-based amplification of the Internally Transcribed Spacer region 2, followed by fragment size analysis on the ABI Prism 310 for the identification of clinically important yeasts . RESULTS: A rapid DNA-extraction method, based on simple boiling freezing was introduced . Of the 25 species tested, 22 could be identified unambiguously by scoring the length of the ITS2-region . No distinction could be made between the species T . asteroides and T . inkin and between T . mucoides and T . ovoides . The two varieties of Cryptococcus neoformans (var . neoformans and var . gattii) could be differentiated from each other due to a one bp length difference of the ITS2 fragment . The three C . laurentii isolates were split in two groups according to their ITS2-fragment lengths, in correspondence with the phylogenetic groups described previously . Since the obtained fragment lenghts compared well to those described previously, an internationally usable library of ITS2 fragment lengths can be constructed . CONCLUSIONS: The existing ITS2 size based library enables identification of most of the clinically important yeast species, within 6 hours starting from a single colony, can be easily updated when new species are described . Data can be exchanged between laboratories. Mol Microbiol, 2002 Aug, 45(3), 837 - 49 Isolation and characterization of capsule structure mutant strains of Cryptococcus neoformans; Moyrand F et al.; The capsule of Cryptococcus neoformans is the most obvious virulence factor of this pathogenic yeast . The main capsule constituents are glucuronoxylomannans (GXM) . Although several studies have focused on GXM composition and structure, very little is known about their genetics . To elucidate the relationship between the capsule structure and the pathophysiology of the cryptococcosis, genetic screening for mutant strains producing a structurally modified capsule was set up . Using monoclonal antibodies specific for different capsule sugar epitopes, we isolated strains with different mutated capsule structures (Cas mutants) . According to their reactivities with various monoclonal antibodies, the mutants were classified into six groups (Cas1 to Cas6) . One Cas2 mutant was used to clone the corresponding gene by complementation . This gene (USX1) encodes the previously identified UDP-xylose synthase . We demonstrated that it is necessary for both capsule xylosylation and C . neoformans virulence. Am J Trop Med Hyg, 2002 Feb, 66(2), 200 - 7 Etiology of encephalitis syndrome among hospitalized children and adults in Takeo, Cambodia, 1999-2000; Srey VH et al.; Whether or not Japanese encephalitis virus (JEV) is an important causative agent of acute encephalitis in Cambodia remains unclear . This study was carried out to determine the cause of encephalitis syndrome among children and adults admitted to Takeo Provincial Hospital from October 1999 to September 2000 . Ninety-nine cases were included in the study: 52 pediatric cases (12 were fatal) and 47 adult cases (10 were fatal) . A causative agent such as human herpesvirus (HHV-3 or HHV-4), Cryptococcus neoformans, or Mycobacterium tuberculosis had been identified in 8 of the 11 adults who had human immunodeficiency virus type 1 (HIV-1) . An infectious agent was identified in 35 (40%) of 88 HIV-1-seronegative patients (60% of the causes remains unidentified) . These comprised 11 bacterial infections, 1 fungal infection, and 23 viral infections . The viral infections were 1 fatal HHV-4 infection, 5 dengue virus infections (2 fatal), 1 coinfection with flavivirus and alphavirus, and 16 presumptive infections JEV (no virus detected), one case of which was fatal . Infection with JEV, the principal cause identified in the 99 encephalitis syndromes, concerned 16 (31%) of 52 children. Arch Pharm Res, 2002 Jun, 25(3), 215 - 28 AIDS related opportunistic infections, going but not gone; Samuel R et al.; It is now more than two decades since the AIDS epidemic began with a cluster of Pneumocystis carinii pneumonia (PCP) in a community of homosexual men . Since then, many other infections have been characterized as opportunistic infections secondary to HIV infection . These include, but are not limited to, infections with Toxoplasma gondii, Cytomegalovirus (CMV), Mycobacterium avium complex (MAC), and Cryptococcus neoformans . Over the last two decades, there have been dramatic improvements in diagnosis, prevention and treatment of all these infections . As a result, in North America and Western Europe the rates of opportunistic infections secondary to AIDS have decreased substantially . We will review these common opportunistic infections below. J Immunol, 2002 Aug 1, 169(3), 1379 - 86 Isotype can affect the fine specificity of an antibody for a polysaccharide antigen; McLean GR et al.; Ab specificity is determined by V region sequence . The murine Mab 18B7 (IgG1) binds to the Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan and produces annular immunofluorescence (IF) on yeast cells . The heavy and light V regions of 18B7 were expressed with the human C regions micro, gamma 1, gamma 2, gamma 3, gamma 4, and alpha1, and the specificity and binding properties of these mouse-human chimeric (ch) Abs was determined . The chIgG1, chIgG2, chIgG4, and the chIgA produced annular IF, whereas the IgM and IgG3 produced punctate IF, despite identical V region sequences . Competition experiments with murine Abs that competed with mAb 18B7 and binding assays to peptide mimetics of glucuronoxylomannan provided additional evidence for altered specificity in some of the ch Abs . Expression of 18B7 heavy V region with murine micro C region produced IgM with a punctate IF, indicating that a change in fine specificity also accompanied the change from murine IgG1 to IgM . Our results show that Ab fine specificity can be a function of isotype . This phenomenon may be most apparent for Abs that bind to Ag with repeating epitopes, such as polysaccharides, where the quarternary structure of the Ag-Ab complex may be influenced by such constraints as Fab-Fab angles, Fc-Fc interactions, Ab size, and solvent accessibility to exposed surfaces . Alterations in Ab fine specificity following isotype change could have important implications for current concepts on the generation of secondary Ab responses to certain Ags and for the isotype preference observed in Abs to polysaccharides. Crit Care Med, 2002 Jul, 30(7), 1419 - 24 Cryptococcal encephalitis in thermally injured mice is accelerated by type 2 T-cell responses; Furukawa K et al.; OBJECTIVE: To explore the pathogenic role of burn-associated type 2 T-cell responses on the development of cryptococcal encephalitis in mice with severe thermal injuries . DESIGN: Experimental Cryptococcus neoformans infection in normal mice was compared with that in thermally injured mice (TI mice), normal mice treated with a mixture of interleukin (IL)-4 and IL-10, or normal mice inoculated with burn-associated type 2 T cells . SETTING: University research laboratory . SUBJECTS: Male BALB/c mice, 8 to 10 wks of age . INTERVENTIONS: We prepared four groups of mice as follows: a) normal mice, b) TI mice, c) normal mice treated with the IL-4/IL-10 mixture, and d) normal mice inoculated with burn-associated type 2 T cells . These groups of mice were anesthetized and exposed to 1 x 10 cells/mouse of C . neoformans intratracheally . Cryptococcal growth in brains and lungs in normal mice were compared with those of the other three groups . Also, cytokine-producing profiles of T lymphocytes from brains of both normal mice and TI mice were determined . MEASUREMENTS AND MAIN RESULTS: Compared with normal mice, TI mice were susceptible to C . neoformans infection . At the maximum (15 days after infection), numbers of C . neoformans organisms in brains of TI mice were 10 times higher than those of the pathogen in brains of normal mice . After stimulation with anti-CD3 monoclonal antibody, IL-4 (but not interferon gamma) was produced in cultures of T lymphocytes from brains of TI mice 15 days after the infection, whereas the same cell preparation from normal mice produced interferon gamma (but not IL-4) . TI mice and mice that were treated with a IL-4/IL-10 mixture or inoculated with burn-associated type 2 T cells were equally susceptible to the cryptococcal infection . CONCLUSIONS: Burn-associated type 2 T cells or their cytokine products play a key role in the severity of cryptococcal encephalitis that develops in TI mice. Curr Infect Dis Rep, 2002 Aug, 4(4), 332 - 338 Management of Increased Intracranial Pressure in Cryptococcal Meningitis; Gambarin KJ et al.; Therapy of cryptococcal meningitis has been focused primarily on optimizing the antifungal regimen to improve the previously high treatment failure rates . Until recently, relatively little attention has been paid to the impact of increased intracranial pressure, which is a frequent problem that complicates management of patients with cryptococcal meningitis . Patients with elevated baseline opening pressures have higher titers of cerebrospinal fluid cryptococcal capsular polysaccharide antigen, more frequent headaches, meningismus, papilledema, hearing loss, and pathologic reflexes, as well as increased morbidity and mortality compared with those patients with normal opening pressures . Optimal therapy has not yet been firmly established, but the diagnostic evaluation and available treatment options are reviewed here, including frequent high volume lumbar punctures, lumbar drains, ventriculoperitoneal shunting, and corticosteroids. Glycobiology, 2002 Jul, 12(7), 409 - 20 Molecular analysis of a novel family of complex glycoinositolphosphoryl ceramides from Cryptococcus neoformans: structural differences between encapsulated and acapsular yeast forms; Heise N et al.; Complex glycoinositolphosphoryl ceramides (GIPCs) have been purified from a pathogenic encapsulated wild-type (WT) strain of Cryptococcus neoformans var . neoformans and from an acapsular mutant (Cap67) . The structures of the GIPCs were determined by a combination of tandem mass spectrometry, nuclear magnetic resonance spectroscopy, methylation analysis, gas chromatography-mass spectrometry, and chemical degradation . The main GIPC from the WT strain had the structure Manp(alpha1-3){Xylp(beta1-2)} Manp(alpha1-4)Galp(beta1-6)Manp(alpha1-2)Ins-1-phosphoryl ceramide (GIPC A), whereas the compounds from the acapsular mutant were more heterogeneous in their glycan chains, and variants with Manp(alpha1-6) (GIPC B), Manp(alpha1-6) Manp(alpha1-6) (GIPC C), and Manp(alpha1-2)Manp(alpha1-6)Manp(alpha1-6) (GIPC D) substituents linked to the nonreducing terminal mannose residue found in the WT GIPC A were abundant . The ceramide moieties of C . neoformans GIPCs were composed of a C(18) phytosphingosine long-chain base mainly N-acylated with 2-hydroxy-tetracosanoic acid in the WT GIPC while in the acapsular Cap67 mutant GIPCs, as well as 2-hydroxy-tetracosanoic acid, the unusual 2,3-dihydroxy-tetracosanoic acid was characterized . In addition, structural analysis revealed that the amount of GIPC in the WT cells was fourfold less of that in the acapsular mutant. Immunity, 2002 Jun, 16(6), 791 - 802 CR3 (CD11b/CD18) and CR4 (CD11c/CD18) are involved in complement-independent antibody-mediated phagocytosis of Cryptococcus neoformans; Taborda CP et al.; IgM and IgA to the Cryptococcus neoformans capsular glucuronoxylomannan (GXM) promote complement-independent phagocytosis by macrophages with efficiency comparable to that of IgG1 . IgM- and IgA-mediated phagocytosis of C . neoformans was proportional to CR3 expression, inhibited by Abs to CR3 (CD11b/CD18) and CR4 (CD11c/CD18), and dramatically reduced with macrophages of CD18-deficient mice . IgM and IgA promoted ingestion of yeast cells by CHO cells expressing CR3 and CR4 . In contrast, IgG1-mediated phagocytosis was only partially inhibited by Abs to CR3 and CR4 . Phagocytosis by IgM and IgA but not IgG1 was inhibited by soluble GXM, which binds CD18 . Involvement of CR in antibody-mediated complement-independent phagocytosis indicates a new link between innate and adaptive immune systems. Southeast Asian J Trop Med Public Health, 2002 Mar, 33(1), 85 - 91 Necropsy in HIV-infected patients; Viriyavejakul P et al.; Human immunodeficiency virus (HIV)infection is usually followed by opportunistic infections, especially in the full-blown acquired immunodeficiency syndrome (AIDS) . This study details the histopathological changes of different organs in relation to HIV infection, with particular emphasis on the opportunistic infections . Various organs from seventeen HIV-infected patients were collected by necropsy and analyzed for histopathological changes . The major histopathological changes included cytomegalovirus infection, cryptococcosis, penicilliosis, bacterial pneumonia, cryptosporidiosis, pneumocystosis, candidiasis, tuberculosis, granulomatosis of unknown etiology, early cirrhosis and chronic active hepatitis . General organ changes from seventeen cases of HIV-infected patients were described and discussed. Endocr Pathol, 1998 Autumn, 9(3), 217 - 223 The Thyroid in Acquired Immunodeficiency Syndrome; Lima MK et al.; Forty-seven thyroids obtained at autopsy from patients with acquired immunodeficiency syndrome (AIDS) with no clinical manifestations of thyroid disease were analyzed systematically in order to determine the frequency and the major pathological characteristics of thyroid involvement in these individuals . The glands were obtained from 38 men and 9 women aged (on average) 33.6 yr . The specimens were weighed, measured, and evaluated after fixation in formalin Histological examination was performed on at least 10 macroscopically normal and altered areas . The anatomopathological lesions detected in 29 glands (613%) were chronic nonspecific focal inflammation (482%); mycobacteriosis and colloid goiter (172%); histoplasmosis, cryptococcosis, and lipomatosis (133%), and paracoccidioidomycosis and hyperplastic nodules (3A%) . Although thyroid disease had not been clinically diagnosed, thyroid involvement was elevated (613%) and in 14 cases (293%) it was related to the immunodeficiency, with mycobacteria being the most common opportunistic agents . There appears to be no report of the association of lipomatosis with AIDS, although this was a frequent finding in the present study (13 7%), exceeding by far the rates reported in the literature (1-2%) . Thus, thyroid lesions are frequent in AIDS patients, occurring in two thirds of the patients studied, especially those with disseminated infection. Glia, 2002 Aug, 39(2), 184 - 8 MHC class II-positive perivascular microglial cells mediate resistance to Cryptococcus neoformans brain infection; Aguirre K et al.; Acquired resistance to the CNS pathogen Cryptococcus neoformans is mediated by CD4(+) T lymphocytes primed by exposure to antigen in the context of major histocompatibility class II (MHC II) molecules . In mouse brain, parenchymal and perivascular microglial cells may express interferon-gamma (IFN-gamma)-inducible MHC class II marker and thus interact with CD4(+) T cells . Primed effector T cells are retained in the infected CNS if antigen is encountered in proper MHC context and may deliver signals that potentiate microglia to enhanced fungistasis . Vaccinated C57BL6/J mice resist an ordinarily lethal C . neoformans rechallenge, but identically treated congenic Abeta(o/o) mice (MHC class II-deficient; CD4(+) T-cell-deficient) do not . Nor can Abeta(o/o) mice be adoptively immunized by infusion of lymphocytes from vaccinated C57BL6/J donors, as are severe combined immunodeficient (SCID) mice (MHC class II-intact, lymphocyte-deficient) . Chimeric (C57BL/6J:Abeta(o/o)) mice with class II expression likely on perivascular microglia only were, like SCID mice, capable of adoptive immunization against C . neoformans brain infection . To the contrary, chimeric mice with class II expression likely only on parenchymal microglia were not capable of effective adoptive immunization against C . neoformans brain infection . Therefore, in order to mediate resistance to infection, primed CD4(+) T cells must interact with the replenishable perivascular microglial subset that lies in close proximity to cerebral vasculature . Although T cells may supply help in the form of inflammatory cytokines to parenchymal microglia, expression of class II on these cells appears unnecessary for antifungal activity . Can J Microbiol, 2002 May, 48(5), 463 - 7 Cryptococcus tephrensis, sp.nov., and Cryptococcus heimaeyensis, sp.nov.; new anamorphic basidiomycetous yeast species from Iceland; Vishniac HS; Two new species from Iceland are described on the basis of physiological profiles and sequence data from the D2 region of LSU rDNA: Cryptococcus tephrensis (type ICE99-IToM Y5, ATCC MYA-1765, CBS 8935, GenBank AF317208) and Cryptococcus heimaeyensis (type ICE99-IToM Y8, ATCC MYA-1759, CBS 8933, GenBank AF370717) . The two new species are identifiable from sequence data and can be distinguished from their closest relative, Cryptococcus victoriae, by their higher maximum temperatures for growth, failure to utilize nitrate as sole nitrogen source, and utilization of cadaverine and ethylamine as sole nitrogen sources . Cryptococcus tephrensis is distinguishable from C . heimaeyensis by failure to grow on saccharate as sole source of carbon and energy. J Infect, 2002 Apr, 44(3), 185 - 8 Intramedullary abscess resulting from disseminated cryptococcosis despite immune restoration in a patient with AIDS; Rambeloarisoa J et al.; We report on a case of cryptococcal intramedullary abscess, which occurred three years after a disseminated cryptococcosis and two years after a lymph node cryptococcal recurrence in a HIV-infected patient who exhibited a long-standing immune restoration . At the time of diagnosis, CD4(+) lymphocyte-count was 640x10(6)/l and HIV viral load was undetectable . Spinal involvement is rare during cryptococcosis of the central nervous system . As far as we are aware, there is only one case of proven intramedullary cryptococcal abscess reported in the literature and this case is then the second one . The significant and sustained increase in CD4 count following effective antiretroviral therapy was probably associated with only a partial immune restitution that did not allow to avoid the occurrence of the cryptococcal medullar abscess . Finally, this case raises the question of when to stop secondary prophylaxis of cryptococcal disease after increase in CD4 cell count under antiretroviral therapy . J Microbiol Immunol Infect, 2002 Jun, 35(2), 89 - 93 Comparison of bone marrow studies with blood culture for etiological diagnosis of disseminated mycobacterial and fungal infection in patients with acquired immunodeficiency syndrome; Ker CC et al.; The role of bone marrow examination in the diagnosis of prolonged fever in patients with human immunodeficiency virus infection remains controversial . This study compared the results of bone marrow examination and blood culture in the evaluation of opportunistic infections in 100 patients with acquired immunodeficiency syndrome who presented with prolonged fever and/or pancytopenia from November 1995 through August 1998 . Bone marrow and blood specimens were routinely submitted for bacterial, mycobacterial, and fungal cultures, and histopathological examination of the bone marrow specimens was also performed . A total of 33 cases of disseminated mycobacterial infections and 17 cases of disseminated fungal infections were identified . Fifteen cases of mycobacterial infection and 8 cases of fungal infection were identified by using bone marrow culture . The causative organisms included Mycobacterium avium complex (9 isolates), Mycobacterium tuberculosis (4), Mycobacterium chelonae (1), Mycobacterium kansasii (1), Cryptococcus neoformans (3), and Penicillium marneffei (5) . Granulomas were seen in only 8 of 33 disseminated mycobacterial infections, and acid-fast bacilli were detected in only 4 patients . Although bone marrow culture did not provide a significantly higher diagnostic yield than blood culture, bone marrow culture plus histopathological examination had a higher diagnostic yield than blood culture alone for patients with disseminated mycobacteriosis . This study demonstrated that bone marrow examination provides an additional aid in the diagnosis of disseminated mycobacterial or fungal infections in patients with human immunodeficiency virus who had prolonged fever. Folia Microbiol (Praha), 2002, 47(3), 302 - 4 Fungal diseases of the respiratory tract; Dorko E et al.; The proportion of Candida and non-Candida species in the clinical material from patients with respiratory-tract diseases was determined . C . albicans was isolated in 102 cases . An additional 89 strains of yeasts, isolated in association with respiratory diseases, belonged to 10 non-albicans Candida spp . and Cryptococcus spp . The prevailing species, which occurred in 47 cases, was C . parapsilosis . C . tropicalis, C . glabrata, and C . guilliermondii were isolated in 12, 10, and 9 cases, respectively . Four strains of C . krusei and three strains of C . lusitaniae and one strain each of C . freyschussii, C . robusta, C . zeylanoides, and Cryptococcus neoformans were also isolated. Rev Alerg Mex, 2002 Mar-Apr, 49(2), 57 - 9 {Hyper-IgM syndrome: mucocutaneous lesions and neutropenia}; Escarcega-Barbosa D et al.; The hyper-IgM syndrome is a rare immunodeficiency disease in which the ability of B cells to switch immunoglobulin production from IgM to IgG, IgA and IgE is defective . The deficiency of IgG and IgA leads to recurrent infections of the respiratory tract, but some patients are susceptible to infection with opportunistic microorganisms, such as Cryptococcus neoformans, and also are prone to neutropenia and mucocutaneous ulcerations . We report a case of a two-year-old boy that was given the diagnosis of the hyper-IgM syndrome on the basis of low serum concentrations of IgG and IgA and high serum levels of IgM associated with C . neoformans infection, neutropenia and mucocutaneous ulcerations . Intravenous immune globulin improves dramatically the disorder, including neutropenia . To date, periodical infusion of immune globulin has prevented the development of serious infections. Curr Opin Investig Drugs, 2002 Apr, 3(4), 555 - 61 Ravuconazole Eisai/Bristol-Myers Squibb; Arikan S et al.; Eisai and Bristol-Myers Squibb (BMS) are developing the triazole, ravuconazole, as a potential treatment for fungal infection {187888} . Eisai selected the compound for further development on the basis of its good safety profile and well-balanced antifungal activity {187888} . Ravuconazole has a broader antifungal spectrum than fluconazole and itraconazole, particularly against strains of Candida krusei and Cryptococcus neoformans {271854}, {342757}, {370312} . By June 1999, the compound was undergoing phase II trials {327113} . In November 2001, it was reported that BMS was seeking a co-development partner for the compound {430011} . In October 2001, analysts at ABN Amro predicted sales of US $50 million in 2003 {444020}. J Nat Prod, 2002 Jun, 65(6), 856 - 9 New sesquiterpenoids from the root of Guatteria multivenia; Zhang Z et al.; A phytochemical investigation of the CHCl(3) fraction of an ethanol extract of the root of Guatteria multivenia furnished nine compounds, of which four are sesquiterpenes (1-4) and five are alkaloids (5-9) . Of the four sesquiterpenes, two are new (1, 3), named guatterin A (1) and dihydromadolin-K (3), and two are known (2, 4), identified as madolin-K (2) and madolin-W (4) . The five known alkaloids were identified as liriodenine (5), lysicamine (6), lanuginosine (7), guadiscine (8), and O-methylpallidine (9) . All the known compounds were isolated from this species for the first time . Structures of the new compounds were determined by extensive NMR studies, including DEPT, COSY, HMQC, HMBC, and NOESY . Compound 7 showed weak inhibitory effect against Candida albicans secreted aspartic proteases (SAP) with IC(50) of 45 microg/mL . Compound 5 was found to have antimicrobial activity against C . albicans, Cryptococcusneoformans, Staphylococcus aureus, and methicillin-resistant S . aureus (MRS) with IC(50)/MIC values of 3.5/6.25, 2.0/12.5, 2.0/3.13, and 2.0/3.13 microg/mL, respectively. Antibiot Khimioter, 2002, 47(2), 7 - 10 {Minimum inhibitory concentrations of various antifungal agents against Basidiomycetes clinical isolates}; Arzumanian VG; The basidiomycete yeasts are often isolated from clinical samples . A minimal inhibiting concentrations (MIC) of ten antifungals of different groups--azols, allilamines, polyens etc.--against isolates of Rhodotorula, Cryptococcus {symbol: see text} Trichosporon yeasts genera were estimated . No one of these cultures was sensitive to azoles at concentrations 0-256 mcg/ml . A vitality of cultures after incubation during 10 days with antifungals was investigated . Miramistin was the most potent fungicidal agent against all cultures. Rev Neurol, 2002 Apr 1-15, 34(7), 618 - 21 {Clinical features of cerebral toxoplasmosis in Cuban patients with AIDS}; Hernandez-Gonzalez E et al.; INTRODUCTION . Neurotoxoplasmosis (NTX) is one of the commonest opportunist infections in patients infected by the human immunodeficiency virus . It presents with a variety of clinical features in the immunocompromised patient . PATIENTS AND METHODS . We made a horizontal retrospective descriptive study of 88 patients with a diagnosis of NTX treated in the Pedro Kour Institute during a three years period . Our aim was to find which were the most common forms of clinical presentation in our setting and to evaluate the use of paraclinical examinations in reaching the presumptive diagnosis . The patients had clinical examinations, CSF studies, detection of indirect immunofluorescence titres (IFI) for Toxoplasma, imaging studies (CAT) and lymphocyte counts . RESULTS . The commonest symptoms were: headache in 79%, fever in 55.68%, motor defect in 44.31% and disorders of consciousness in 29.54% of the patients . The IFI titres were negative in 31.54% of the patients, between 1/16 and 1/32 in 38.34% and between 1/64 and 1/1,024 in only 30.07% of cases . The T CD4+ lymphocyte count was less than 200 cells in 66.7% of the patients; 72% of imaging studies showed typical lesions, in association with other disorders in 38% of the cases (lymphomas, cryptococcosis, tuberculous meningoencephalitis and cytomegalovirus encephalitis) . CONCLUSIONS . NTX in a patient with AIDS often presents in our setting with headache and fever, motor deficit and alterations of consciousness . The diagnosis should be confirmed by immunological or imaging studies since in this disease serology and CSF studies are less specific. FEMS Microbiol Lett, 2002 Jun 18, 212(1), 1 - 6 Organization of mitochondrial DNA in the basidiomycetous Dioszegia hungarica (Cryptococcus hungaricus) species; Gacser A et al.; The organization of mitochondrial DNA was investigated in the six collection strains of the basidiomycetous yeast Dioszegia hungarica (Cryptococcus hungaricus) isolated so far . Physical and partial functional maps were constructed . Two strains (CBS 6324 and 6576) were identical while three others (CBS 4214, 5124, 6953) differed not only in the distribution of restriction sites but in gene order as well . Results confirm the hypothesis that these five strains are representatives of different closely related species . The sixth strain CBS 6569 revealed a unique mitochondrial genome organization . Its mtDNA separated into eight bands on agarose gel without enzymatic digestion . These molecules carried mitochondrial genes, and RFLP analysis of the four largest molecules using frequently-cutting restriction enzymes (KpnI and SmaI) showed them to have strongly homologous sequences . This unique mtDNA organization was also observed in a strain of Cystofilobasidium capitatum, providing evidence that CBS 6569 belongs to the Cystofilobasidium clade. Curr Genet, 2002 Apr, 41(1), 43 - 7 Epub 2002 Apr 03. Mitochondrial DNA polymorphisms in the human pathogenic fungus Cryptococcus neoformans; Xu J; This study examined mitochondrial DNA (mtDNA) restriction site polymorphisms among 416 strains of the human pathogenic yeast Cryptococcus neoformans from the United States and Japan . The strains included 378 serotype A, 14 serotype D, 18 serotype AD, two serotype B, and two strains whose serotype could not be determined using current commercial monoclonal antibodies . Portions of two genes were examined: (1) the mitochondrial large ribosomal RNA gene (mtLrRNA) and (2) the NADH dehydrogenase subunit 2 ( ND2) . To screen for polymorphisms among the 416 strains, the endonuclease MaeIII was used to digest the PCR-amplified mtLrRNA gene fragment and three endonucleases ( BanI, AluI, MseI) were used to digest the PCR-amplified ND2 gene fragment . Four mtDNA haplotypes were identified among these strains . All strains of serotype A had mtDNA haplotype I, strains of serotype D had haplotype II, and strains of serotype B had haplotypes III and IV . Of the two non-typable strains, one was haplotype I while the other was haplotype II . Among the strains of serotype AD, 14 were haplotype I and the other four were haplotype II . These results were discussed in the context of recent findings regarding the origins of serotype AD strains and the observed uniparental mtDNA inheritance in laboratory crosses between strains of serotypes A and D. Ann Trop Paediatr, 2002 Jun, 22(2), 125 - 31 The post-mortem pathology of HIV-1-infected African children; Chakraborty R et al.; A retrospective review of autopsy findings and medical records in 33 HIV-infected children living in a Kenyan orphanage is described . Their ages ranged from 1 month to 18 years and median age at death was 71 months (range 7-156) . Respiratory disorders were probably the primary cause of death in 21 (64%), in 19 (90%) of whom pyogenic parenchymal lung disease was detected . A presumptive clinical diagnosis of pulmonary tuberculosis had been made in 14 (67%); these children also had a history of recurrent acute lower respiratory tract infections (more than four infections/year) . At autopsy, however, only one case of tuberculosis was identified (disseminated disease) . Pneumocystis carinii pneumonia was not identified . Primary bacterial meningitis was detected in 33% . The associated findings included disseminated Kaposi sarcoma in two children and cryptococcal meningitis in one child . It is concluded that pyogenic infections are common causes of morbidity and mortality in HIV-1-infected African children . Management should include prompt treatment and, if indicated, prophylaxis for recurrent bacterial infections, and early evaluation and treatment of pulmonary tuberculosis. Semin Respir Infect, 2002 Jun, 17(2), 158 - 81 State-of-the-art review of pulmonary fungal infections; Wheat LJ et al.; The endemic mycoses are restricted geographically based on environmental and other factors that favor the growth of these organisms in the soil . Histoplasmosis and blastomycosis mostly afflict patients in the Mississippi and Ohio River Valleys whereas coccidioidomycosis occurs primarily in the desert southwest United States . Cryptococcosis also may present as pulmonary disease, particularly in persons with cellular immune impairment . These mycoses are increasing in importance as causes for opportunistic disease in immunocompromised patients, especially those with acquired immune deficiency syndrome (AIDS) . Aspergillus is a common cause of serious invasive fungal infection in granulocytopenic patients, and may cause lung infection in persons with preexisting pulmonary diseases or atopy . Infections with less virulent fungi, such as Trichosporon, Fusarium, Alternaria, Pseudallescheria, and dematiaceous fungi, are being recognized more frequently . The lung is the portal of entry for most of these pathogens, and often is prominently involved in the clinical syndrome . This article focuses on the recognition, diagnosis, and management of these important pulmonary mycoses . Eur J Med Res, 2002 May 31, 7(5), 242 - 56 Voriconazole -- better chances for patients with invasive mycoses; Ghannoum MA et al.; The past two decades have witnessed an increase in serious fungal infections, without corresponding growth in available antifungal agents . Voriconazole (VRC) is a novel triazole antifungal, recently approved in Europe for treatment of serious infections caused by Aspergillus, Fusarium, Scedosporium, and resistant Candida species . Voriconazole has in vitro activity against yeasts and yeast-like fungi similar, or superior to, fluconazole (FLC), itraconazole (ITC) and amphotericin B (AMB) . Candida albicans is generally the most susceptible yeast (VRC MIC subset90 of 0.06 microg/ml); C . krusei often has low MICs even in the face of FLU/ITC resistance . Voriconazole has demonstrated comparable, or better, in vitro activity than ITC and AMB against Aspergillus (mean MICs 0.19-0.58 microg/ml), Ascomycetes, Bipolaris, Fusarium, Blastomyces dermatitidis, Coccidioides immitis, dermatophytes, Histoplasma capsulatum, Malassezia, and Scedosporium angiospermum (P . boydii) . The drug possesses potent fungicidal activity against moulds including Aspergillus, Scedosporium, and Fusarium . Fungicidal activity is likely due to the high affinity of VRC for fungal 14-alpha-demethylase, a concept supported by ultrastructural and biochemical analysis . Animal studies confirmed the activity of VRC against infections including pulmonary and invasive aspergillosis (IA); A . fumigatus endocarditis; fusariosis; pulmonary cryptococcosis; and invasive candidiasis . Most importantly, well-designed human clinical trials have confirmed the efficacy of VRC in the treatment of candidal esophagitis, IA, and febrile neutropenia . Smaller studies and case reports have shown VRC is useful for salvage therapy of IA, cerebral aspergillosis, Scedosporium, and other fungal infections . Clinical testing has shown VRC is safe and well tolerated; the most common side effect is benign, self-limited visual disturbance. Eur J Med Res, 2002 May 31, 7(5), 200 - 26 Management of mycoses in surgical patients -- review of the literature; Holzheimer RG et al.; Fungal infections have been recognized as major cause of morbidity and mortality in neutropenic and non-neutropenic surgical intensive care patients . The incidence of Candida has increased: it is now the fourth most often isolated pathogen in bloodstream infections . The incidence of Aspergillus infection in transplant patients is highest in heart and lung transplants: 19-26% . Most invasive fungal infections in surgical patients are caused by Candida spp . and Aspergillus spp., less by Cryptococcus spp . and may be classified as local or organ-related, as (chronic) disseminated, and as fungemia . There is no highly specific and sensitive routine test for the diagnosis of Candida and Aspergillus infections available; clinical signs of fungal infections are rather unspecific . The significance of colonization remains undetermined . In non-neutropenic surgical patients central venous access and broad-spectrum antibiotics are independent risk factors for the development of fungal infection . Immunsuppression, e.g., transplantation, burn injury, can render patients susceptible to fungal infection . This has lead to the introduction of antifungal prophylaxis in transplant and burned patients which has reduced the mortality for Candida spp . infection significantly . There is no prophylaxis available against Aspergillus spp . and Cryptococcus spp . Treatment of fungal infections consists of surgical and medical treatment for most organ-related infections . Recommendations for the management of fungal infections exist mostly for neutropenic patients, only few reports address the fungal infection of the surgical intensive care patient . Amphotericin B has been recommended as first line treatment for most severe fungal infections with fluconazole as follow-up treatment . In case of the development of toxic side effects of amphotericin B, mostly fluconazole or lipid formulations of amphotericin were favored . However, a shift in Candida strains towards non-albicans spp . and more resistant species was observed during recent years . This has lead to treatment failures in severe Candida and Aspergillus infections . The prognosis for invasive Aspergillus infections remains poor despite amphotericin B treatment . Newer azoles, e.g . voriconazole, demonstrated stable activity against most of these strains and may offer an option in the treatment of refractory fungal infections. J Microbiol Methods, 2002 Sep, 51(1), 29 - 33 Preparation and characterization of Cryptococcus neoformans synchronous culture; Raclavsky V et al.; We have developed a method for preparation of synchronous culture in Cryptococcus neoformans . The method is based on age fractionation of exponentially growing asynchronous culture through differential sedimentation in 10-20% (w/v) lactose gradient . C . neoformans capsule thickness should be reduced to a minimum to ensure most accurate age fractionation, which is necessary to obtain a higher degree of synchrony . The C . neoformans synchronous culture system has revealed important characteristics with respect to cellular morphology, DNA content and cell volume distribution . The method can be used for further cell cycle studies. Scand J Infect Dis, 2002, 34(5), 397 - 8 Diabetes insipidus as a complication of cryptococcal meningitis in an HIV-infected patient; Juffermans NP et al.; We describe an HIV-infected patient with central diabetes insipidus as a complication of cryptococcal meningitis . Nephrogenic diabetes insipidus as a result of amphotericin B treatment is a rare but known complication . Central diabetes insipidus in cryptococcal meningitis has not been reported before . The patient responded well to desmopressin treatment. Bioorg Med Chem Lett, 2002 Jul 8, 12(13), 1697 - 700 Antifungal Sordarins . Part 4: synthesis and structure--activity relationships of 3',4'-fused alkyl-tetrahydrofuran derivatives; Bueno JM et al.; A series of Sordarin derivatives bearing alkyl substituted tetrahydrofuran rings fused to C3'-C4' bond of the sugar moiety have been prepared and their antifungal properties evaluated . Most of them show remarkable antifungal activity against Candida spp and Cryptococcus neoformans. Infect Immun, 2002 Jul, 70(7), 3363 - 70 Modulation of C5aR expression on human neutrophils by encapsulated and acapsular Cryptococcus neoformans; Monari C et al.; Cryptococcus neoformans and cryptococcal surface polysaccharides influenced C5aR expression on human polymorphonuclear neutrophils (PMN) . Encapsulated and acapsular strains produced dramatically different effects . Treatment of PMN with acapsular cryptococci up-regulated C5aR expression; whereas treatment with encapsulated cells suppressed C5aR expression . Glucuronoxylomannan (GXM), the principal constituent of the cryptococcal capsule, was responsible for such inhibition . Increased C5aR expression following treatment with acapsular cryptococci was accompanied by increased binding of C5a to PMN, increased superoxide production in response to stimulation with C5a, and an increased chemotactic response to C5a . Conversely, decreased C5aR expression following treatment with encapsulated cryptococci or acapsular cryptococci that had been pretreated with GXM was accompanied by decreased binding of C5a to PMN and a decreased chemotactic response to C5a . Our results raise the possibility that the down-regulation of C5aR expression by encapsulated cryptococci might alter PMN function at the site of cryptococcal infection. Scand J Infect Dis, 2002, 34(4), 309 - 10 Cryptococcal breast abscess; Schouten WE et al.; A cryptococcal abscess of the breast is uncommon and may mimic a neoplastic lesion . We describe a patient with an isolated cryptococcal infection of the breast, which was treated with oral fluconazole in combination with surgical excision . With the exception of diabetes mellitus type II, no underlying predisposing illness was identified. Scand J Infect Dis, 2002, 34(4), 284 - 8 Systemic fungal infections after renal transplantation; Altiparmak MR et al.; In a retrospective evaluation, the incidence of systemic fungal infections (SFIs) in 296 kidney graft recipients admitted to our center between 1986 and 1999 was found to be 4% . Eighteen percent of 28 recipients transplanted in India and 8% of 12 recipients transplanted in Russia developed SFI . In contrast, SFI was encountered in only 2% of recipients transplanted at our center . The median time of diagnosis of SFI was 5 months after transplantation . The lungs and central nervous system were the most frequently affected sites . The most common etiologic agent was Aspergillus fumigatus (n = 7) but Candida spp . (n = 1), Rhizopus spp . (n = 1) and Cryptococcus neoformans (n = 1) were also encountered . In 2 patients, 2 different pathogens were isolated at the same time: A . fumigatus and Rhizopus spp . in 1 patient and Candida spp . and A . fumigatus in another . In order to determine predisposing factors for SFI, patients admitted immediately before and after those with SFI were used as controls: long-term hospitalization, long-term antibiotic use and post-transplant diabetes mellitus were found to be predisposing factors . Eight patients were treated with antifungal drugs and a good response to liposomal amphotericin B therapy was obtained in 3/5 . Nine patients (75%) with SFI died . As SFIs are associated with a high mortality rate in renal transplant recipients, antifungal therapy, especially with liposomal amphotericin B, should be started whenever fungal infection is suspected, even before the results of microbiologic and/or histologic examinations are known. J Assoc Nurses AIDS Care, 2002 May-Jun, 13(3), 81 - 99 Clinical aromatherapy and AIDS; Buckle J; Clinical aromatherapy is the use of essential oils for expected outcomes that are measurable and is a therapy that is used as part of nursing care in Switzerland, Germany, Australia, Canada, the United Kingdom, and, more recently, the United States . Essential oils are steam distillates obtained from aromatic plants . These volatile extracts have been used for many years by French hospitals against airborne bacteria and fungi . As antimicrobial agents, essential oils may be appropriate in HIV/AIDS for specific opportunistic infections . Aromatherapy can also alter perceptions of chronic pain, help maintain skin integrity, and is useful in stress management . Methods of application vary depending on the site of infection and the psychological profile of the patient and can include inhalation, compresses, baths, massage, and the "m" technique . This article will explore the potential use of essential oils in HIV/AIDS focusing on four opportunistic infections: Cryptococcus neoformans, Candida albicans, methicillin-resistant Staphylococcus aureus, and herpes simplex types I and II. Clin Infect Dis, 2002 Jul 1, 35(1), 53 - 61 Epub 2002 Jun 05. The impact of novel immunosuppressive agents on infections in organ transplant recipients and the interactions of these agents with antimicrobials; Husain S et al.; Several of the new immunosuppressive agents that are used to treat transplant recipients possess in vitro activity against specific pathogens, enhance the activity of antimicrobial agents, or have unique drug interactions with antimicrobial agents . Mycophenolate mofetil may have a protective effect against Pneumocystis carinii; it also enhances the activity of ganciclovir and has strong antiviral activity against human immunodeficiency virus type 1 . High doses of mycophenolate mofetil have been associated with a higher frequency of tissue-invasive cytomegalovirus disease but not with asymptomatic cytomegalovirus infection . Rapamycin exhibits potent in vitro fungicidal activity against Cryptococcus neoformans and several pathogenic fungi in transplant recipients; however, it is not known whether its immunosuppressive effect in organ transplant recipients outweighs its antifungal activity . Recognition of the unique characteristics of these agents and the evolving spectrum of opportunistic infections has implications for the differential diagnosis, management, and prophylaxis of infections in organ transplant recipients in the modern immunosuppressive era. Med Mycol, 2002 Apr, 40(2), 221 - 3 Cryptococcus neoformans var . gattii meningitis in Singapore; Koh TH et al.; We describe here two cases of Cryptococcus neoformans var . gattii meningitis that occurred in Singapore . This variety of Cryptococcus neoformans differs from the more widely known C . n . var . neoformans in its ecology and epidemiology . Infections with this variety are still rare in Singapore. Folia Microbiol (Praha), 2002, 47(2), 182 - 4 Candidal urinary tract infections caused by non-albicans Candida species; Dorko E et al.; The incidence of non-albicans Candida and non-Candida species isolated from the urine of patients admitted to various departments of the Faculty Hospital of the Medical Faculty of Safarik University in Kosice was examined . From a total of 94 samples of analyzed urine 58 strains of C . albicans and 36 strains of yeasts belonging to 6 species of non-albicans Candida and non-Candida spp . were detected: C . parapsilosis (n = 23), C . tropicalis (6), C . krusei (3), C . robusta (2), C . catenulata (1) and Cryptococcus neoformans (1) . In relation to the diagnosis, the yeasts were isolated from patients suffering from a kidneys disease, epididymitis, diabetes, neoplastic diseases, urogenital anomalies, obstructive uropathy, cystitis, prostatitis, hemolytic-uremic syndrome, and others. Folia Microbiol (Praha), 2002, 47(2), 105 - 12 Causative agents of nosocomial mycoses; Tomsikova A; In the last few years mycoses have been caused by fungi formerly considered to be harmless for humans . They cause diseases of plants and insects; some of them are also used in the industry . They are now usually called "emerging fungi" . We investigated this flora with respect to their potential to cause infections in hospitals . These fungi are present in the air, on medical objects and instrumentation, in the respiratory tract and on the hands of hospital staff; other sources have been identified in the use of iatrogenic methods . Mycotic diseases, their risk factors, their clinical pictures, and spectra of agents were analyzed in 1990-2000; the results were compared with data in the literature . Transplantations were the most frequent risk factors, fungemia and abscess the most frequent clinical picture and filamentous fungi (genera Absidia, Acremonium, Alternaria, Apophysomyces, Aspergillus, Bipolaris, Cladophialophora, Cunninghamella, Exserohilum, Fusarium, Chaetomium, Chrysosporium, Lecythophora, Ochroconis, Paecilomyces, Pythium, Rhizopus, Scedosporium, Scopulariopsis) were the most frequent agents of nosocomial infections . These filamentous fungi and also some yeasts (genera Candida, Cryptococcus, Trichosporon) bring about different clinical syndromes in both immunocompromised and immunocompetent patients. Int J Syst Evol Microbiol, 2002 May, 52(Pt 3), 1033 - 8 Cryptococcus nyarrowii sp . nov., a basidiomycetous yeast from Antarctica; Thomas-Hall S et al.; In December 1997, 196 soil and snow samples were collected from Vestvold Hills, Davis Base, Antarctica . Two isolates, CBS 8804T (pink colonies) and CBS 8805 (yellow colonies), were shown by proteome analysis and DNA sequencing to represent the same species . Results from the sequencing of the D1/D2 region of the large rDNA subunit placed this species in the hymenomycetous tree in a unique sister clade to the Trichosporonales and the Tremellales . The clade consists of Holtermannia corniformis CBS 6979 and CBS strains 8804T, 8805, 8016, 7712, 7713 and 7743 . Morphological and physiological characteristics placed this species in the genus Cryptococcus, with characteristics including the assimilation of D-glucuronate and myo-inositol, no fermentation, positive Diazonium blue B and urease reactions, absence of sexual reproduction and production of starch-like compounds . Fatty acid analysis identified large proportions of polyunsaturated lipids, mainly linoleic (C18:2) and, to a lesser extent, linolenic (C18:3) acids . On the basis of the physiological and phylogenetic data, isolates CBS 8804T and CBS 8805 are described as Cryptococcus nyarrowii sp . nov. Med Mycol, 2001 Oct, 39(5), 419 - 22 First report of Cryptococcus neoformans var . gattii serotype B from Greece; Velegraki A et al.; A plethora of cases of Cryptococcus neoformans infections have been recorded worldwide in immunocompromised individuals . The number of such cases showed a steady rise before 1981 and increased dramatically thereafter due to the AIDS epidemic . A similar pattern has been seen in Greece but, so far, infections appear to have been caused by C . neoformans var . neoformans . This paper describes for the first time two culture-proven C . n . var . gattii serotype B infections in Greece, one in an AIDS patient and one in a patient with systemic lupus erythematosus. Med Mycol, 2001 Oct, 39(5), 409 - 17 Prospective use of RFLP analysis on amplified Cryptococcus neoformans URA5 gene sequences for rapid identification of varieties and serotypes in clinical samples; Velegraki A et al.; Clinical isolates of Cryptococcus neoformans, whole blood, cerebrospinal fluid, bronchoalveolar lavage fluid from patients with positive cryptococcal antigen latex-agglutination test, and spiked clinical material from healthy individuals, were tested by polymerase chain reaction (PCR) with primers amplifying C . neoformans URA5 gene sequences . To test compatibility of different DNA extraction protocols with the PCR-restriction fragment length polymorphism (RFLP) assay, a commercial DNA extraction kit (XTRAX; Gull Laboratories, UT, USA) was used alongside with the hexadecyltrimethylammonium bromide (CTAB) method on spiked biological fluids . Both methods extracted DNA from spiked clinical samples containing C . neoformans (8 +/- 2 cells ml(-1)) and generated amplification products suitable for restriction enzyme analysis . Alu I digestion differentiated the two varieties of C . neoformans . Three distinct RFLP patterns were obtained upon restriction with MspI corresponding to serotypes A, AD and B, C and D . URA5 PCR followed by RFLP analysis, coupled with a sensitive in-house or commercially available DNA extraction method from clinical samples, could be successfully incorporated into rapid routine diagnostic strategies . It could also provide an expeditious tool for epidemiology-based population genetics studies. Med Mycol, 2001 Oct, 39(5), 383 - 6 Isolation of a Cryptococcus neoformans serotype A MATa strain from the Italian environment; Viviani MA et al.; Cryptococcus neoformans is a heterothallic basidiomycete which possesses a bipolar mating system based on two mating type alleles, MATa and MATalpha . In the type variety, C . neoformans var . neoformans, both mating types have been found among strains of one serotype, serotype D, whereas only MATalpha was identified after extensive survey of serotype A strains . Serotype A MA Ta appeared to be extinct or to exist only in a vestigial, non-functional form . We report the isolation of a C . n . var . neoformans serotype A MATa strain from the Italian environment . The strain was serotyped by slide agglutination test, genotyped by polymerase chain reaction (PCR) fingerprinting using the (GACA)4 primer, and its haploid state was determined by flow cytometry . The mating type was identified by PCR amplification of the pheromone a gene . In addition, the amplification of the four STE20 alleles, specific for the mating type of serotypes A and D, showed that the strain contains only the MATa locus . By crossing experiments the strain was found to be fertile . The interest in the finding of this fertile isolate is related to the possibility to construct a congenic pair of serotype A MATa/MATalpha strains to be used in genetic and pathogenesis studies. J Neurovirol, 2002 Jun, 8(3), 158 - 67 Central nervous system infections in individuals with HIV-1 infection; Mamidi A et al.; Opportunistic infections of the central nervous system (CNS) are common complications of advanced immunodeficiency in individuals with human immunodeficiency virus type 1 (HIV-1) infection . Neurological disease is the first manifestation of acquired immunodeficiency syndrome (AIDS) in 10% to 20% of symptomatic HIV-1 infection . Prompt diagnosis and treatment of such disorders is critical . Also, in the era of highly active antiretroviral therapy (HAART), these disease states have changed in presentation and epidemiology . Therefore, we review the epidemiology, pathogenesis, clinical features, diagnosis, and management of five common central nervous system disorders in individuals with HIV-1 infection: toxoplasma encephalitis, primary central nervous system lymphoma, cryptococcal meningitis, cytomegalovirus encephalitis, and progressive multifocal leukoencephalopathy. J Immunother, 2002 Mar-Apr, 25 Suppl 1, S12 - 9 Interleukin-18 and host defense against infectious pathogens; Kawakami K; Host defense to infectious pathogens is largely mediated by neutrophil-, cellular, or humoral immunity or eosinophil-dependent mechanism . Each mechanism preferentially acts against extracellular or intracellular microbial pathogens, viruses, or helminthes . These host defense responses are strictly regulated by two different categories of cytokines, T helper (Th)1 and Th2 cytokines . Interleukin-18, originally found as interferon-gamma-inducing factor, has now been identified to be involved in the development of Th1 and Th2 cells, which suggests the considerable involvement of this cytokine in the protective immune responses against infection . This review focuses on the role of interleukin-18 in the development and regulation of host resistance to infectious pathogens, with an emphasis on the infection with Cryptococcus neoformans, an intracellular fungal pathogen, as determined by recent studies from our laboratory. Immunology, 2002 Jun, 106(2), 267 - 72 Antibody to Cryptococcus neoformans capsular glucuronoxylomannan promotes expression of interleukin-12Rbeta2 subunit on human T cells in vitro through effects mediated by antigen-presenting cells; Vecchiarelli A et al.; The results reported herein show that T cells responding to encapsulated Cryptococcus neoformans cells had reduced expression of interleukin-12 receptor beta2 (IL-12Rbeta2) in comparison to those responding to non-encapsulated cells . This suggested that encapsulation with glucuronoxylomannan (GXM), the principal constituent of the C . neoformans polysaccharide antiphagocytic capsule, inhibited expression of the IL-12Rbeta2 subunit on T cells responding to cryptococcal antigens . Addition of GXM-binding monoclonal antibody (mAb) overcame this effect by promoting IL-12Rbeta2 expression and by decreasing IL-1R expression on T cells . This effect may be a consequence of mAb-induced changes on antigen-presenting cells (APC) that are closely related to increased phagocytosis . Blocking of phagocytosis with monoiodacetic acid (MIA) precluded up-regulation of B7 expression on APC and was associated with diminished IL-12Rbeta2 expression on T cells . The observed effects on T cells were interpreted as a consequence of increased APC function due to enhanced phagocytosis . These findings suggest a mechanism by which specific antibody can promote the polarization of the cellular immune response towards a Th1-like response and thus contribute to an enhanced cellular immune response against C . neoformans. Orbit, 2001 Mar, 20(1), 11 - 23 Fine needle aspiration biopsy in orbital lesions; Rastogi A et al.; PURPOSE . The study was performed to evaluate the efficacy of fine needle aspiration biopsy (FNAB) in orbital lesions . METHODS . Seventeen patients with orbital masses who had been fully investigated by non-invasive techniques participated in this study . FNAB was performed by standard technique, as an outpatient procedure, with ultrasound guidance in lesions posterior to the equator . A trained cytologist analysed all the smears . RESULTS . Specific results were obtained in 14 of the 17 (82%) patients studied by FNAB . Ten cases were neoplastic (8 malignant and 2 benign), 3 were inflammatory and 1 was a case of histiocytosis X . In 3/17 cases the results were non-specific . These were treated as pseudotumours and responded well to systemic steroids . In 7 cases the clinical and radiological diagnosis was confirmed by FNAB . Non-invasive investigations like USG, CT and MRI, however, failed to provide accurate diagnosis in the other 7 (41%) cases . In these patients, FNAB yielded a pathological diagnosis (histiocytosis X, cryptococcosis, non Hodgkin's lymphoma, adenocarcinoma, pleomorphic adenoma, Schwannoma and cysticercosis), helping us to modify treatment with an excellent response . No significant complications were encountered following the aspiration biopsies . CONCLUSION . FNAB proved to be a reliable method for distinguishing between malignant and non-malignant lesions . It was found to be rapid, accurate, cost-effective, safe and a valuable addition to ultrasound, CT scan and MRI in the diagnosis of orbital lesions . This tool may help in avoiding a traumatic surgical intervention . Southeast Asian J Trop Med Public Health, 2001 Dec, 32(4), 776 - 8 Initial treatment with amphotericin B plus rifampin in the acute treatment of cryptococcal meningitis in aids; Chotmongkol V et al.; The result of initial treatment with amphotericin B (0.7 mg/kg/day) plus rifampin (600 mg/day) for 2 weeks, followed by fluconazole (400 mg/day) for 8 weeks in the acute treatment of cryptococcal meningitis in AIDS is reported . There were 10 patients in the study: at 2 weeks, all had made a clinical response and cerebrospinal fluid was sterile in 4 patients; at 10 weeks, all had negative cerebrospinal fluid cultures . Serious side effects were not detected. J Clin Microbiol, 2002 Jun, 40(6), 2095 - 100 Multicenter comparison of three different analytical systems for evaluation of DNA banding patterns from Cryptococcus neoformans; Cardinali G et al.; The enormous improvement of molecular typing techniques for epidemiological and clinical studies has not always been matched by an equivalent effort in applying optimal criteria for the analysis of both phenotypic and molecular data . In spite of the availability of a large collection of statistical and phylogenetic methods, the vast majority of commercial packages are limited by using only the unweighted pair group method with arithmetic mean algorithm to construct trees and by considering electrophoretic pattern only as migration distances . The latter method has serious drawbacks when different runs (separate gels) of the same molecular analysis are to be compared . This work presents a multicenter comparison of three different systems of banding pattern analysis on random amplified polymorphic DNA, (GACA)(4), and contour-clamped homogeneous electric field patterns from strains of Cryptococcus neoformans var . neoformans isolated in different clinical and geographical situations and a standard Saccharomyces cerevisiae strain employed as an outgroup . The systems considered were evaluated for their actual ability to(i) recognize identities, (ii) define complete differences (i.e., the ability to place S . cerevisiae out of the C . neoformans cluster), and (iii) estimate the extent of similarity among different strains . The ability to cluster strains according to the patient from which they were isolated was also evaluated . The results indicate that different algorithms do indeed produce divergent trees, both in overall topology and in clustering of individual strains, thus suggesting that care must be taken by individual investigators to use the most appropriate procedure and by the scientific community in defining a consensus system. J Clin Microbiol, 2002 Jun, 40(6), 2041 - 5 Detection of antibodies specific to an antigenic cell wall galactomannoprotein for serodiagnosis of Aspergillus fumigatus aspergillosis; Chan CM et al.; Aspergilloma and invasive aspergillosis are important opportunistic infections caused by Aspergillus species, among which Aspergillus fumigatus is the most common species associated with human disease . We developed an enzyme-linked immunosorbent assay (ELISA)-based antibody assay with Afmp1p, a purified recombinant antigenic cell wall galactomannoprotein of A . fumigatus . Evaluation of the test with guinea pig sera against A . fumigatus and other pathogenic fungi indicated that this assay was specific for A . fumigatus . Clinical evaluation revealed that the assay was 100% sensitive for patients with aspergilloma and 33.3% sensitive for patients with invasive aspergillosis . No false-positive results were found for serum samples from 80 healthy blood donors, 6 patients with typhoid fever, 4 patients with melioidosis, 20 patients with penicilliosis marneffei, 5 patients with candidiasis, and 4 patients with cryptococcosis, indicating a high specificity of the test . Thus, this ELISA-based test for the detection of anti-Afmp1p antibody can be of significant value as a diagnostic for aspergillosis. Pharm Res, 2002 Apr, 19(4), 418 - 22 Block copolymer micelles for the encapsulation and delivery of amphotericin B; Lavasanifar A et al.; PURPOSE: To assess the effect of fatty acid substitution of a micelle-forming poly(ethylene oxide)-block-poly(N-hexyl stearate-L-aspartamide) (PEO-b-PHSA) on the encapsulation, hemolytic properties and antifungal activity of amphotericin B (AmB) . METHODS: PEO-b-PHSA with three levels of stearic acid substitution were synthesized and used to encapsulate AmB by a solvent evaporation method . Size exclusion chromatography and UV spectroscopy were used to confirm and measure levels of encapsulated AmB . The hemolytic activity of encapsulated AmB toward human red blood cells and its minimum inhibitory concentration against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans were obtained and compared to AmB alone . RESULTS: An increase in the level of stearic acid substitution on PEO-b-PHSA improved the encapsulation of AmB while reducing its hemolytic activity . PEO-b-PHSA micelles having 50% and 70% stearic acid substitution (mol fatty acid: mol reacted and unreacted hydroxyls) were completely non-hemolytic at 22 microg/ml . At 11% stearic acid substitution, AmB caused 50% hemolysis at 1 microg/ml . AmB in PEO-b-PHSA micelles was as effective as AmB alone against pathogenic fungi . CONCLUSIONS: PEO-b-PHSA micelles with a high level of stearic acid side chain substitution can effectively solubilize AmB, reduce its hemolytic activity yet retain its potent antifungal effects. Clin Infect Dis, 2002 Jun 15, 34(12), E64 - 8 Epub 2002 May 17. Use of ventriculoperitoneal shunts to treat uncontrollable intracranial hypertension in patients who have cryptococcal meningitis without hydrocephalus; Liliang PC et al.; Between 1997 and 2000, 4 human immunodeficiency virus-negative patients in our institution had cryptococcal meningitis with uncontrollable intracranial hypertension . All 4 patients were treated with antifungal drugs as well as ventriculoperitoneal (VP) shunts for intracranial hypertension . Neurological deficits that were unresponsive to pharmacologic treatment were resolved by use of the VP shunt . Uncontrollable elevation of intracranial pressure associated with cryptococcal meningitis can be resolved by use of a VP shunt, even when imaging studies do not reveal hydrocephalus. Bioorg Med Chem Lett, 2002 Jun 3, 12(11), 1473 - 6 Identification of novel antifungal nonapeptides through the screening of combinatorial peptide libraries based on a hexapeptide motif; Kundu B et al.; Four sets of mixture based nonapeptide libraries derived from an antifungal hexapeptide pharmacophore Arg-D-Trp-D-Phe-Ile-D-Phe-His-NH(2) (II) have been synthesized . The three C-terminal positions 7, 8 and 9 were subject to randomization using 19 genetically coded amino acids . They were then screened for their antifungal activity against Candida albicans and Cryptococcus neoformans in order to quantify inhibition at each step of the nonapeptide sublibrary deconvolution . The studies led to the identification of several novel nonapeptides with potent antifungal activity . Two of the nonapeptides exhibited approximately 17-fold increase in the activity in comparison to the lead hexapeptide motif His-D-Trp-D-Phe-Phe-D-Phe-Lys-NH(2) (I) against C . albicans. Microb Ecol, 2001 Aug, 42(2), 201 - 207 Microbial Ecology of the Mango Phylloplane; Jager ES et al.; Bacteria, filamentous fungi, and yeasts were enumerated on the mango phylloplane by indirect leaf impression and washing- and dilution plating . The phylloplane microbial community was qualitatively and quantitatively related to leaf age, position in the tree canopy, seasonality, and chemical spraying . Filamentous fungi and yeasts were more abundant during winter and spring, whereas bacterial population densities increased during autumn . Community density and diversity increased progressively with leaf age . The western tree aspect sustained the least diverse bacterial, filamentous fungal, and yeast communities . Chemical sprays reduced bacterial, filamentous fungal, and yeast community diversities . Gram-positive bacteria (Bacillus spp . and coryneform spp.) exceeded gram-negative bacteria . The most common fungal genera isolated were Cladosporium and Alternaria . Yeasts prevalent in the mango phylloplane were of the genera Aureobasidium, Cryptococcus, and Sporobolomyces. J Comput Assist Tomogr, 2002 May-Jun, 26(3), 330 - 4 Pulmonary cryptococcosis: CT and pathologic findings; Zinck SE et al.; PURPOSE: The purpose of this work was to describe the CT and pathologic findings of pulmonary cryptococcosis . METHOD: CT scans of 11 patients (7 immunocompromised, 4 immunocompetent) with proven pulmonary cryptococcosis were analyzed for number, morphologic characteristics, and distribution of parenchymal abnormalities as well for presence of lymphadenopathy and pleural effusion . Pathology of lung specimens obtained by open biopsy or resection (n = 5) and transbronchial biopsy (n = 1) was reviewed by one dedicated pulmonary pathologist . RESULTS: Pulmonary nodules, either solitary or multiple, were the most common CT finding, present in 10 of 11 patients (91%); associated findings included masses (n = 4), CT halo sign (n = 3), and consolidation (n = 2) . On histologic examination, focal areas of ground-glass attenuation surrounding or adjacent to nodules were found to represent airspace collections of macrophages and proteinaceous fluid . CONCLUSION: Pulmonary cryptococcosis should be considered in the differential diagnosis of solitary or multiple pulmonary nodules (with or without associated CT halo sign), particularly in immunocompromised patients. J Appl Physiol, 2002 Jun, 92(6), 2608 - 16 Experimental and calculated parameters on particle phagocytosis by alveolar macrophages; Camner P et al.; Phagocytosis of three types of fluorescein-labeled test particles by rat alveolar macrophages (AM) were studied: spherical silica (3.2 microm), heat-killed Candida albicans (3.8 microm), and heat-killed Cryptococcus neoformans (6.1 microm) opsonized with specific IgG . These particles should attach to scavenger, mannose, and Fc receptors, respectively . Both control AM and AM pretreated for 20 h with interferon-gamma (12.5 or 50 U/ml) were studied . The sum of the number of attached and ingested particles per AM (accumulated attachment) was used as a measure of the attachment process, and the number of ingested particles per AM divided by the accumulated attachment (ingested fraction) was used as a measure of the ingestion process . The average ingestion time (IT), which is also a measure of the ingestion process, was calculated from the experimental data . The ingestion process was independent of the attachment process . IT increased with the time of observation . This is explained by the fact that IT determined from observation times shorter than the whole distribution of IT for a certain particle results in a shorter IT than the real average IT . C . albicans (mannose receptor) had the fastest ingestion process, C . neoformans opsonized with specific IgG (Fc receptor) had ingestion that was nearly as fast, and the silica particles (scavenger receptors) had the slowest ingestion process . Treatment with interferon-gamma markedly impaired the attachment process for all three types of particles (and three types of receptors) but clearly impaired the ingestion process only for silica particles (scavenger receptors). Infect Immun, 2002 Jun, 70(6), 2959 - 64 Induction of interleukin-12 and gamma interferon requires tumor necrosis factor alpha for protective T1-cell-mediated immunity to pulmonary Cryptococcus neoformans infection; Herring AC et al.; The development of T1-cell-mediated immunity is required to clear a pulmonary Cryptococcus neoformans infection . The objective of these studies was to determine the mechanism by which tumor necrosis factor alpha (TNF-alpha) augments the development of pulmonary T1 immunity to C . neoformans infection . TNF-alpha expression was detected in lavage sample cells at days 2, 3, and 7 following C . neoformans infection . The numbers of CFU in the lung were not different between control and anti-TNF-alpha-treated mice at any time point examined during the afferent phase of the response (days 0 to 7) . However, neutralization of TNF-alpha prevented the initiation of pulmonary clearance during the efferent phase of the response (day 14) . Administration of anti-TNF-alpha monoclonal antibody (day 0) diminished the lung levels of TNF-alpha, interleukin-12 (IL-12), and gamma interferon (IFN-gamma) induced by C . neoformans at day 7 postinfection . Neutralization of TNF-alpha (day 0) also altered the IFN-gamma/IL-4 ratio in the lung-associated lymph nodes at day 7 following C . neoformans infection . Anti-TNF-alpha-treated mice developed a pulmonary eosinophilia at day 14 postinfection . Consistent with the pulmonary eosinophilia, anti-TNF-alpha-treated mice exhibited elevated serum immunoglobulin E and inhibition of the anticryptococcal delayed-type hypersensitivity response, indicating a shift toward a T2 response . Neutralization of IL-12 also prevented lung leukocyte production of IFN-gamma in response to the infection . These findings demonstrate that afferent-phase TNF-alpha production is essential for the induction of IL-12 and IFN-gamma and neutralization of early TNF-alpha results in a T2 shift of the T1/T2 balance of antifungal immunity. Infect Immun, 2002 Jun, 70(6), 2812 - 9 Fc-dependent and Fc-independent opsonization of Cryptococcus neoformans by anticapsular monoclonal antibodies: importance of epitope specificity; Netski D et al.; Monoclonal antibodies (MAbs) reactive with glucuronoxylomannan (GXM), the major capsular polysaccharide of the yeast Cryptococcus neoformans, produce distinct capsular reactions when viewed by differential interference contrast microscopy . These reactions depend on the epitope specificity of the antibody . Opsonic activities of immunoglobulin G1 (IgG1) MAbs that produce patterns termed rim and puffy were examined . Rim-pattern MAbs are reactive with an epitope shared by GXM serotypes A, B, C, and D . Puffy-pattern MAbs are reactive only with serotypes A and D . In phagocytosis assays, using serotype A cells and resident murine peritoneal macrophages, rim-pattern MAbs were markedly more opsonic than puffy-pattern MAbs . F(ab')(2) fragments of rim-pattern MAbs were synergistic with heat-labile factors in normal human serum for opsonization of the yeast . F(ab')(2) fragments of puffy-pattern MAbs were also synergistic with normal serum in opsonization but at a much lower level than fragments of rim-pattern MAbs . Normal serum alone was not opsonic . F(ab')(2) fragments of rim-pattern MAbs, but not puffy-pattern MAbs, stimulated phagocytosis of encapsulated cryptococci in the absence of serum . This serum-independent opsonic action of F(ab')(2) fragments was abrogated by pretreatment of macrophages with purified GXM, suggesting the involvement of a phagocyte GXM receptor . The results indicate that (i) there are multiple mechanisms by which anticapsular IgG MAbs facilitate phagocytosis of encapsulated cryptococci, (ii) some anti-GXM antibodies are opsonic in an Fc-independent manner, and (iii) opsonic activity correlates with the capsular reaction and occurs in an epitope-specific manner. Microbiol Immunol, 2002, 46(3), 181 - 6 Anti-CD11 b monoclonal antibody suppresses brain dissemination of Cryptococcus neoformans in mice; Kawakami K et al.; To elucidate the role of the beta2 integrin family of adhesion molecules in the disseminated infection of Cryptococcus neoformans from the lung to the central nervous system, we examined the effects of monoclonal antibodies (mAbs) against CD11a, CD11b, CD11c and CD18 on the number of live microorganisms in both the lung and brain of mice three weeks after intratracheal infection . Administration of anti-CD11b mAb partially, but reproducibly, reduced the fungal loads in the brain in three independent experiments, while the lung loads were not affected . In addition, the same treatment significantly decreased the number of live microorganisms in the blood . In sharp contrast, the brain loads one week after intravenous injection with C . neoformans were not affected by treatment with anti-CD11b mAb . Finally, administration of mAb against other adhesion molecules (CD11a, CD11c or CD18) failed to affect the fungal loads in the brain as well as in the lung three weeks after intratracheal instillation, except for anti-CD18 mAb which rather increased the brain loads . Our results suggested that CD11b might be involved at least in part in the process of fungal dissemination from lung to brain, although the significance of other beta2 integrin family adhesion molecules remains to be substantiated. FEMS Microbiol Lett, 2002 Apr 9, 209(2), 175 - 81 Strain-dependent effects of environmental signals on the production of extracellular phospholipase by Cryptococcus neoformans; Wright LC et al.; Extracellular phospholipase (PL) activities comprising phospholipase B, lysophospholipase and lysophospholipase transacylase have been identified in culture supernatants of Cryptococcus neoformans and contribute to virulence . We found that PL production was optimal after fungal growth at 30 degrees C and secretion at 37 degrees C for all six C . neoformans isolates studied (four C . neoformans var . neoformans and two C . neoformans var . gattii) . No increase in PL activity was found in one strain, NU-2, in low iron or tissue culture media, conditions where upregulation of other virulence factors has been reported . The most virulent strains in an intravenous mouse model of infection were best able to produce PL at growth and secretion temperatures of 37 degrees C, in tissue culture media and under assay conditions of pH 7.0. J Electron Microsc (Tokyo), 2002, 51(1), 21 - 7 Electron microscopy of pathogenic yeasts Cryptococcus neoformans and Exophiala dermatitidis by high-pressure freezing; Yamaguchi M et al.; A high-pressure freezing method was used to observe the ultrastructure of pathogenic yeasts, Cryptococcus neoformans and Exophiala dermatitidis, after freeze-substitution and ultrathin sectioning . The method well preserved the cell structure in its natural state, since the capsule, cell wall, plasma membrane, nucleus, outer and inner nuclear membranes, nuclear pores, nucleolus, mitochondria, mitochondrial membrane and cristae, vacuoles, endoplasmic reticulum, Golgi apparatus, spindle pole body, ribosomes, lipid droplets, microtubules, actin filaments, and glycogen granules were clearly visible . The method was shown to freeze cells as deep as 0.1 mm by sectioning the sample perpendicular to specimen surface . The quality of the cell image was similar to that obtained by a rapid freezing method when compared using the same materials . Thus, high-pressure freezing would be useful for making serial ultrathin sections for three-dimensional analysis of cells, which should give basic information of structure and function of pathogenic yeast cells necessary for finding an effective therapy for mycoses. Mycoses, 2002 Apr, 45(3-4), 132 - 4 Case reports . Isolation of two Trichosporon cutaneum strains from urine; Gokahmetoglu S et al.; Two strains of Trichopsoron cutaneum were isolated from the urine of two male patients . Antifungal susceptibility and cross-reactivity with Cryptococcus antigen latex agglutination text as well as the patients' situation are reported. Mycoses, 2002 Apr, 45(3-4), 111 - 7 Case Reports . Pulmonary cryptococcosis associated with cryptococcal meningitis in non-AIDS patients; Zhu LP et al.; We report four cases of pulmonary cryptococcosis associated with cryptococcal meningitis in non-HIV infected patients . All four patients had no apparent symptoms and signs of focal lesions that necessitate evaluation for the pulmonary lesion . Two out of four patients had radiologic evidence of pulmonary cavitation and mass lesions simultaneously, an uncommon finding in non-AIDS patients . Diagnostic and therapeutic problems of pulmonary cryptococcosis associated with cryptococcal meningitis are discussed. Mycoses, 2002 Apr, 45(3-4), 75 - 8 Comparative evaluation of Candi Select test and conventional methods for identification of Candida albicans in routine clinical isolates; Foongladda S et al.; The Candi Select test (Sanofi Diagnostics, Pasteur, Marnes-La-Coquette, France) is a new yeast-selective medium for the identification of Candida albicans in the clinical laboratory . The performance of this test was compared with the conventional methods of chlamydospore formation, germ tube formation and carbohydrate fermentation . Four hundred and twenty clinical yeast isolates from 412 fresh clinical specimens, including 283 C . albicans, 59 C . tropicalis, 39 Trichosporon spp., 19 C . glabrata, 11 Cryptococcus neoformans and 9 other yeasts, were evaluated . Colonies of C . albicans produced a blue-green colour on the Candi Select media which could be distinguished from the other yeasts with the naked eye within 24-48 h . The sensitivity and specificity of the Candi Select test for the identification of C . albicans were 99.65% and 97.08%, respectively . The blue-green colonies of C . albicans were easy to identify and recognize in mixed cultures and did not need detailed microscopic examination. Mycoses, 2002 Apr, 45(3-4), 65 - 74 Antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'-trimethoxyphenyl)-2-nitro-ethylene; Pettit RK et al.; The antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'-trimethoxyphenyl)-2-nitro-ethylene (TMPN) were examined . TMPN was fungicidal for the majority of 132 reference strains and clinical isolates tested, including those resistant to fluconazole, ketoconazole, amphotericin B or flucytosine . Minimum fungicidal concentration/minimum inhibitory concentration (MFC/MIC) ratios were < or = 2 for 96% of Cryptococcus neoformans clinical isolates and 71% of Candida albicans clinical isolates . TMPN was fungicidal for a variety of other basidiomycetes, endomycetes and hyphomycetes, and its activity was unaffected by alterations in media pH . The frequency of occurrence of fungal spontaneous mutations to resistance was <10(-6) . Kill-curve analyses confirmed the fungicidal action of TMPN, and demonstrated that killing was concentration- and time-dependent . At sub-MIC exposure to TMPN, C . albicans did not exhibit yeast/hyphae switching . TMPN was slightly cytotoxic for murine and human cancer cell lines (GI50=1-4 microg ml(-1)), and weakly inhibited mammalian tubulin polymerization (IC50=0.60 microg ml(-1)). Mycopathologia, 2002, 153(3), 133 - 5 Repeated isolation of Cryptococcus laurentii from the oropharynx of an immunocompromized patient; Bauters TG et al.; Cryptococcus laurentii is one of the non-neoformans cryptococci that have rarely been isolated from humans . We report a case of repeated colonization of the oropharynx by Cr . laurentii in a patient with erythroleukaemia . The isolate was identified by phenotypic and genotypic tests and showed resistance to fluconazole. Mycopathologia, 2002, 153(3), 121 - 4 Occurrence of yeasts in psittacines droppings from captive birds in Italy; Mancianti F et al.; Three-hundred twenty five droppings from parrots raised in the premises of 4 breeders and in several private households were cultured for yeasts . One-hundred sixty droppings (49.2%) resulted positive . From these specimens 212 isolates belonging to 27 different species were obtained . Mainly Candida species such as C . albicans, C . catenulata, C . curvata, C . famata, C . glabrata, C . guilliermondi, C . holmii, C . intermedia, C . krusei, C . lambica, C . lusitaniae, C . membranaefaciens, C . parapsilosis, C . pelliculosa, C . sake and C . valida were isolated . Debarvomyces marama, D . polymorphus, Geotrichum sp., Pichia etchelsii, P . ohmeri, Rhodotorula glutinis, R . rubra, Rhodotorula sp., Saccharomyces cerevisiae, S . kluyiveri and Zygosaccharomyces sp . were also obtained . Dark colonies on Staib medium were never observed . The psittacine birds apparently serve as carriers for several Candida species or their perfect states and to a lesser extent for other opportunistic yeasts such as Rhodotorula, Trichosporon and Saccharomyces spp., which are considered part of the transient microbiota of the gastrointestinal tract . The most striking finding was the absence of Cryptococcus spp . among the isolates . The present survey confirms the role of pet birds in carrying potential zoonotic yeasts. J Med Microbiol, 2002 May, 51(5), 423 - 32 Increased release of glucuronoxylomannan antigen and induced phenotypic changes in Trichosporon asahii by repeated passage in mice; Karashima R et al.; Clinically important fungi such as Candida albicans and Cryptococcus neoformans are known to undergo phenotypic changes after repeated subculture or passages in vivo . However, there are no reports describing this phenomenon in Trichosporon species . This study investigated whether in-vivo passages of environmental isolates of Trichosporon asahii in mice changes their phenotype; three environmental isolates and 14 clinical isolates (from deep-seated infections) were used . The shape of the colony and cell type were observed, and the titre of glucuronoxylomannan (GXM) antigen and concentration of (1-->3)-beta-D-glucan were measured for each isolate . Changes in these features were also examined after three passages of the environmental isolates in mice . The shape of colonies and cell types were clearly different in environmental and clinical isolates . Furthermore, the clinical isolates released significantly higher levels of GXM antigen than environmental isolates (titre: log2 9.4 SD 0.7 versus log2 5.4 SD 1.4) . The phenotype of passaged isolates was significantly different from the original environmental isolates with respect to the morphology of colonies and cell type and GXM release (titre: log2 10.0 SD 0.7 versus log2 5.4 SD 1.4) . These results suggest that the phenotypic changes in T . asahii occur as a result of in-vivo passages . This process may allow a proportion of the fungal population to escape eradication by the host immune system, as GXM antigen is considered to protect the fungi against phagocytosis by polymorphonuclear leucocytes and monocytes in vivo. Przegl Epidemiol, 2001, 55 Suppl 3, 91 - 9 {The essence of infection by opportunistic microorganisms}; Zaremba ML; Infection is regarded as an imbalance between microbial pathogenicity factors and the host defense systems . Opportunistic infections are defined as infections rarely observed in humans with normal immune responses . The term immunocompromised (compromised) host refers to host in which one or more defence mechanisms are inactive and in which the probability of infection is therefore increased . Hospital patients are often compromised host . Compromised hosts exist even outside the hospital (smoking, intravenous drug use, poor nutrition and other) . A good example is HIV (human immunodeficiency virus) . HIV causes acquired immunodeficiency syndrome (AIDS) by destroying the CD4 T lymphocytes, involved in the immune response . The most common AIDS-associated opportunistic infections include pneumonia caused by the fungus Pneumocystis carinii, systemic candidiasis (Candida albicans) and cryptococcosis (Cryptococcus neoformans), protozoal infections such as cryptosporidiosis (Cryptosporidium spp.) and toxoplasmosis (Toxoplasma gondii), viral infections due to HSV, CMV, EBV, HPV or HHV8, tuberculosis and other bacterial infections . Pneumocystis carinii pneumonia (PCP) is the most common opportunistic disease observed in AIDS patients . Disease does not necessarily follow exposure to a given causal agent (pathogen 01 opportunistic pathogen) . In fact, the occurrence (or otherwise) of disease typically depends on various factors--including the degree of sensitivity of the host (as above) and the virulence factors of the pathogens . Overtly aggressive products such as toxins and aggressins are clearly virulence factors . However, so too are those products and strategies which help a pathogen to become established in the host and to evade the host's defences . Certain virulence factors can be induced in the pathogen via signal transduction pathways from environment. Chirality, 2002 May 15, 14(5), 449 - 54 Chiral discrimination by HPLC and CE and antifungal activity of racemic fenticonazole and its enantiomers; Quaglia MG et al.; Fenticonazole is a chiral antifungal agent, used in therapy as the racemic mixture . The investigation on the chirality of fenticonazole is reported in this study . rac-Fenticonazole was resolved by HPLC and by capillary electrophoresis (CE) . The chiral stationary phase (CSP), used in HPLC, was Daicel OD-H, a commercial phase, which allowed the separate collection of the two enantiomers . The chiral selectors used for CE were some cyclodextrin derivatives . The analysis time required from CE was about the half the HPLC enantioseparation time . The biological activity of the rac-mixture and each individual enantiomer was tested against Cryptococcus neoformans and two Aspergillus nidulans strains . The minimum inhibitory concentration (MIC) evaluation showed that the eutomer was the enantiomer chromatographically more retained and had a longer migration time in the electrophoretic enantioseparation . The CD spectrum of the eutomer showed a positive Cotton effect . J Basic Microbiol, 2002, 42(2), 111 - 9 Intra-strain variability of Cryptococcus neoformans can be detected on phloxin B medium; Kucsera J et al.; A method was devised for easy detection of intra-strain variability of the human pathogenic yeast Cryptococcus neoformans . Cultivation of strains on a medium containing Phloxin B resulted in different coloured colonies . Generally, colonies were either pink or red; however there were also several colony-colour segregant in which both colours could be observed . A number of these segregants were isolated and analysed . Virulence factors such as the cell and capsule sizes were measured; further temperature sensitivity, growth rates, mating-types and melanin production were also studied . Segregants were examined by random amplified polymorphic DNA (RAPD) fingerprinting and electrophoretic karyotyping by pulsed-field gel electrophoresis (CHEF) . They showed both phenotypic and genotypic differences . The main differences appeared in phenotypic characters and RAPD patterns; while the chromosomal patterns remained unchanged . Reversion frequency analysis revealed that the reason for this segregation could be due to phenotypic switching . The physiological reason for the colour changes was also investigated and was attributed to the differential ability of the cells to accumulate Phloxin B either into their capsules or into their cells . The method described here is potentially applicable for the detection of strain heterogeneity in both basic and clinical microbiology laboratories. J Immunol, 2002 May 1, 168(9), 4659 - 66 Differential roles of CC chemokine ligand 2/monocyte chemotactic protein-1 and CCR2 in the development of T1 immunity; Traynor TR et al.; CCR2 and its major ligand, chemokine ligand 2 (CCL2)/monocyte chemotactic protein-1, have been found to influence T1/T2 immune response polarization . Our objective was to directly compare the roles of CCR2 and CCL2 in T1/T2 immune response polarization using a model of pulmonary Cryptococcus neoformans infection . Either deletion of CCR2 or treatment of wild-type mice with CCL2 neutralizing Ab produced significant and comparable reductions in macrophage and T cell recruitment into the lungs following infection . Both CCL2 neutralization and CCR2 deficiency resulted in significantly diminished IFN-gamma production, and increased IL-4 and IL-5 production by lung leukocytes (T1 to T2 switch), but only CCR2 deficiency promoted pulmonary eotaxin production and eosinophilia . In the lung-associated lymph nodes (LALN), CCL2-neutralized mice developed Ag-specific IFN-gamma-producing cells, while CCR2 knockout mice did not . LALN from CCR2 knockout mice also had fewer MHCII(+)CD11c(+) and MHCII(+)CD11b(+) cells, and produced significantly less IL-12p70 and TNF-alpha when stimulated with heat-killed yeast than LALN from wild-type or CCL2-neutralized mice, consistent with a defect in APC trafficking in CCR2 knockout mice . Neutralization of CCL2 in CCR2 knockout mice did not alter immune response development, demonstrating that the high levels of CCL2 in these mice did not play a role in T2 polarization . Therefore, CCR2 (but not CCL2) is required for afferent T1 development in the lymph nodes . In the absence of CCL2, T1 cells polarize in the LALN, but do not traffic from the lymph nodes to the lungs, resulting in a pulmonary T2 response. J Vet Dent, 2000 Dec, 17(4), 177 - 81 Pr