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Biomedical subjects

G Morace

Publications and source records attributed to G Morace.

At least 73 records · Page 4Linked to original sources

'Antibiobodies': antibiotic-like anti-idiotypic antibodies.

Pathogenic micro-organisms such as Candida albicans may be susceptible to the activity of antimicrobial products like yeast killer toxins due to the presence of specific cell wall receptors for these agents. Anti-idiotypic antibodies (anti-Ids) were produced that competed for these receptors with the yeast killer toxin of a strain of Pichia anomala. We report here that affinity chromatography purified anti-Ids may kill C. albicans cells in vitro which are susceptible to the activity of the yeast killer toxin, as well as P. anomala killer cells which are obviously immune to their own toxin despite possessing specific cell wall receptors which can be detected by indirect immunofluorescence with anti-Ids. We propose that these conceptually new antimicrobial immunoglobulins acting as antibiotics be called 'antibiobodies'.

Anti-Bacterial Agents↗

In-vitro comparative activity of fluconazole and other antifungal agents against Blastoschizomyces capitatus.

Blastoschizomyces capitatus represents an emerging fungal pathogen in acute leukemia patients. The susceptibility to amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole of nine clinical isolates was evaluated. A specific medium (high resolution medium) was used for testing fluconazole. This agent and 5-fluorocytosine were at least four- to eight-fold more active than amphotericin B and ketoconazole against all isolates but one.

Antifungal Agents↗

In vitro susceptibility of 119 yeast isolates to fluconazole, 5-fluorocytosine, amphotericin B and ketoconazole.

The in vitro activity of fluconazole was tested against 13 yeast species (119 strains) isolated from clinical specimens during a 3-month period. For comparative purposes, three other antifungal compounds (5-fluorocytosine, amphotericin B and ketoconazole) were also tested. The tests were carried out using a microautomated method previously developed in our laboratory. The method allowed us to determine the minimum inhibitory concentration (MIC) of the four antifungal drugs used. For each of the drugs we utilized different media. The MIC ranges (mg/l) of fluconazole were: 0.04-12.5 for Candida albicans, 0.19-6.25 for Candida parapsilosis, 12.5-50 for Candida krusei, 0.04-100 for Candida tropicalis, 0.04- greater than 100 for Candida glabrata, 0.09- greater than 25 for Cryptococcus neoformans, 0.09-0.78 for Saccharomyces cerevisiae, 6.25- greater than 100 for Trichosporon beigelii and 0.09-0.19 for Blastoschizomyces capitatus (Trichosporon capitatum). The MIC value (mg/l) was 0.39 for Candida guilliermondii and Candida lusitaniae, greater than 100 for Cryptococcus laurentii and 0.09 for the 3 isolates of Torulopsis candida. These results were obtained using the medium recommended for in vitro testing of fluconazole (high-resolution medium) by Pfizer UK.

Amphotericin B↗

Interfaces of the yeast killer phenomenon.

A new prophylactic and therapeutic antimicrobial strategy based on a specific physiological target that is effectively used by killer yeasts in their natural ecological competition is theorized. The natural system exploited is the yeast killer phenomenon previously adopted as an epidemiological marker for intraspecific differentiation of opportunistic yeasts, hyphomycetes, and bacteria. Pathogenic microorganisms (Candida albicans) may be susceptible to the activity of yeast killer toxins due to the presence of specific cell wall receptors. On the basis of the idiotypic network, we report that antiidiotypic antibodies, produced against a monoclonal antibody bearing the receptor-like idiotype, are in vivo protecting animals immunized through idiotypic vaccination and in vitro mimicking the antimicrobial activity of yeast killer toxins, thus acting as antibiotics.

Adsorption↗

Detection by immunofluorescent anti-idiotypic antibodies of yeast killer toxin cell wall receptors of Candida albicans.

Yeast killer toxin cell wall receptors of Candida albicans were observed by indirect immunofluorescence using an affinity purified rabbit anti-idiotypic antiserum. The antiserum had been raised against a monoclonal antibody neutralizing the in vitro activity of a killer toxin produced by a selected strain of Hansenula anomala UCSC 25F. This simple procedure permitted the location of killer toxin cell wall receptors in various morphological phases of the yeast cells. The use of the indirect immunofluorescence technique with anti-idiotypic antibodies may have potential value in determining the occurrence of killer toxin receptors in other microbial systems.

Antibodies, Anti-Idiotypic↗

Epidemiological and clinical aspects of mycoses in patients with AIDS-related pathologies.

Mycological, cultural and/or serological studies were performed on 98 patients hospitalized in the Department of Infectious Diseases of the Catholic University in Rome with diagnoses of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) diseases. The incidence of mycoses was evaluated by retrospectively analyzing the results of mycological examinations and comparing them with clinical manifestations. The presence of concomitant bacterial, viral and parasitic infections was also examined. For epidemiological purposes, the study was extended to include the biotyping of all yeasts isolated from patients hospitalized between September 1988 and February 1989 in the same Department. Antimycotic susceptibility was also determined for the first yeast isolate obtained from each of these patients. Oral candidiasis (50 cases) caused by Candida albicans was the most frequent mycosis, followed by esophageal candidiasis (13 cases) and cryptococcosis (6 cases). Four out of the 6 cryptococcosis patients had meningeal involvement. Systemic candidiasis (2 cases) and aspergillosis (1 case) were less common. Biotyping of yeasts isolated between September 1988 and February 1989 with the killer system revealed type 377 to be the most common among the C. albicans isolates. It represented 70% of all the yeasts isolated.

AIDS-Related Complex↗

Production of yeast killer toxin in experimentally infected animals.

The ability of a killer yeast (Pichia anomala, UCSC 25F) to produce toxin in vivo was demonstrated, for the first time, in tissues of normal and immunosuppressed experimentally infected mice by means of a fluorescent antibody technique and a killer toxin specific monoclonal antibody. The possible significance of the findings is discussed.

Animals↗

Nosocomial outbreak of systemic candidosis associated with parenteral nutrition.

Eight patients in two surgical units developed systemic candidosis during a 40-day period from June 5 to July 13, 1987 (in five cases Candida albicans was identified). Three of them died. All cases belonged to a group of 27 patients receiving parenteral nutrition (PN), while among the 108 patients who did not receive PN, no cases were observed (p = .000001). Candida was cultured from two PN bags administered to the cases. A specialized nutrition nurse was responsible for the PN compounding and for maintaining administration sets in the two wards involved. An epidemiological investigation, in which 19 uninfected patients who had had PN were used as controls, showed no significant difference between cases and controls except that lipids were more frequently added to bags administered to cases (p = .0005). Furthermore, the bags administered to cases contained a higher average number of multidose constituents (p = .0008) when the comparison was focused on the two days before the onset of symptoms. Given the favorable medium provided by lipids, even a low level contamination of PN solutions during compounding and/or administration could have been responsible for the exposure of cases to multidose vials suggests, although not conclusively, that an extrinsic contamination occurred during compounding. Six isolates of C albicans were available from four cases. C albicans was cultured from the pharyngeal swabs of two physicians and three nurses, including the specialized nutrition nurse.

Aged↗

HIV genome in peripheral blood mononuclear cells of seronegative regular sexual partners of HIV-infected subjects.

We have investigated the presence of the human immunodeficiency virus (HIV) by using in situ hybridization on peripheral blood mononuclear cells (PBMCs) from seronegative regular sexual partners of HIV-infected subjects. The cells were hybridized with a 9 kilobase (kb) Sstl-Sstl lambda BH 10 probe, which was able to recognize both viral mRNA and proviral cDNA. Labeling was done by chemical insertion of an antigenic sulfone group in cytosine moieties and was visualized by a double-antibody immunohistochemical reaction. In all the subjects studied, the HIV genome was present. The HIV infected cells showed morphological aspects consistent with that of lymphocytes and monocytes. Our data suggest that the anti-HIV seronegative individuals who are regular sexual partners of HIV-infected subjects may be HIV-infected.

Bisexuality↗

Prevalence of HBeAg, anti-HBe serological markers and HBV-DNA in asymptomatic carriers in Ethiopia.

Data on the distribution of HBV-DNA and other serological markers of hepatitis B virus infection in a population of asymptomatic carriers in Ethiopia are reported. As compared to data from other countries of similar or lower levels of endemicity, it has been found that HBV-DNA prevalence and its correlation with HBeAg/anti-HBe status is similar to that of northern Europe. HBV-DNA is present in 84% of HBe Ag-positive sera but in only 4% of anti-HBe-positive sera, where the lowest concentration of DNA (less than 5 pgr/20 microliters) was found. The trend of increasing prevalence of serological markers with age seems to indicate a considerable horizontal transmission still present in this age range (18-30). In keeping with data of other authors a 3% of HBV-DNA positivity in anti HBc only positive sera was found. No regional or ethnical differences of HBV-DNA positive sera across the country were observed. There is also no evidence of any correlation between HBV-DNA prevalence and HBsAg subtypes ad and ay.

Adolescent↗

Biotyping of bacterial isolates using the yeast killer system.

Forty-four presumptive killer yeasts were tested against bacterial isolates, including rapid-growing gram-positive and gram-negative bacteria, as well as slow-growing bacteria, such as the mycobacteria. A killer system, based on the patterns of bacterial susceptibility to the action of nine selected killer yeasts, was developed for epidemiological purposes. The killer system, previously standardized for yeasts and hyphomycetes, was adapted to the specific growth conditions of the bacterial isolates. The results obtained confirm that susceptibility to the yeast killer phenomenon is widespread among microorganisms unrelated to yeasts and that it could form the basis for a convenient and adaptable biotyping method in microbiological laboratories.

Bacterial Typing Techniques↗

Studies on the epidemiology of Aspergillus fumigatus infections in a university hospital.

The impact of the airborne opportunistic fungus pathogen, Aspergillus fumigatus in patients hospitalized at the university hospital of Parma, Italy, and its outpatients was investigated during a period of six months. Sputum and bronchial washings were collected from 986 patients. The 2,437 specimens were culturally examined for the presence of A. fumigatus regardless of the patient's clinical diagnosis. This fungus was isolated from 32 patients (3.2%). Subsequently, immunological tests for aspergillosis were performed on 22 of these culture-positive patients. Eight of these patients (36.4%) were serologically proven to be affected by aspergillosis. The 32 A. fumigatus isolates were epidemiologically investigated by the killer system to determine the mode of spread of these infections. Among the patients, fifteen different biotypes were differentiated, and their value in studying the epidemiology of aspergillosis in the hospital environment was investigated.

Adolescent↗

Serological study of yeast killer toxins by monoclonal antibodies.

Yeast killer toxins coded by determined and undetermined killer plasmids or presumptive nuclear gene(s) in various genera (Saccharomyces, Kluyveromyces, Pichia and Candida) have been serologically investigated by a monoclonal antibody (KT4), produced against the yeast killer toxin of Pichia (Hansenula) anomala UCSC 25F. Double immunodiffusion with the killer toxins as antigens and indirect immunofluorescence on whole cells of the corresponding killer yeast have been used. In both the serological procedures, monoclonal antibody KT4 proved to be reacting only with the killer toxins and the whole cells of yeasts belonging to the genus Pichia.

Antibodies, Monoclonal↗

Biotyping of pathogenic fungi by the killer system and with monoclonal antibodies.

Biotyping of pathogenic yeasts and hyphomycetes based on their susceptibility to selected killer yeasts and their reactivity with monoclonal antibodies are described. Both methods were used to differentiate fungi isolated from patients providing valuable epidemiological information on mycotic infections. The functional biotyping obtained with the two systems and the conventional auxenographic biocoding approaches commercially available for opportunistic yeasts are comparatively evaluated. The potential for biotyping of industrial fungal isolates is also discussed.

Antibodies, Monoclonal↗

HBV and HIV expression in lymph nodes of HIV positive LAS patients: histology and in situ hybridization.

The presence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) was investigated using hybridization in 15 lymph nodes and one Kaposi's sarcoma skin lesion obtained from HIV-positive patients. Cryostat tissue sections were hybridized with chemically modified DNA probes for HBV and HIV. HIV genome was mainly observed in the cytoplasm of cells present in 7/15 lymph nodes and in the Kaposi's sarcoma skin lesion, thus indicating the expression of HIV replication. Control samples hybridized with an HTLV I probe were negative. HBV genome was found in the cytoplasm of lymphoid mononuclear cells in 2/7 lymph nodes, obtained from HIV+ patients without serum markers of ongoing HBV infection. Lymph node positivity for HBV DNA also confirms that lymphoid cells may be a target for HBV. Since HBV infection seems to precede HIV infection in nearly all patients, it is possible that it may represent a factor facilitating the development of the HIV-related disease.

AIDS-Related Complex↗

Yeast killer toxins and dimorphism.

The differential action of four selected yeast killer toxins on the mycelial and yeast forms of four isolates of the dimorphic fungus Sporothrix schenckii was comparatively evaluated. The results confirmed that the yeast killer phenomenon is present among hyphomycetes and yeasts and that both morphological forms of S. schenckii are susceptible to the action of the same yeast killer toxin. Quantitative differences in the response to the killer action of the mycelial and yeast forms in individual strains were also observed. To avoid retroconversion of the dimorphic forms, we used a modification of the conventional killer system.

Colony Count, Microbial↗