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T L Ray

Publications and source records attributed to T L Ray.

17 recordsLinked to original sources
PubMed1990

Comparative production and rapid purification of Candida acid proteinase from protein-supplemented cultures.

Six Candida spp. that were previously characterized for cutaneous pathogenicity were assessed for Candida acid proteinase (CAP) production in albumin-supplemented, nitrogen-restricted media. C. albicans CAP production was compared in media supplemented with albumin, casein, collagen, hemoglobin, or keratin and in TC medium 199. C. albicans, C. stellatoidea, and C. tropicalis, which are cutaneous pathogens in murine infections, produced 3.3 to 4.7 times more CAP than did the nonpathogens C. parapsilosis and C. guilliermondii. C. krusei, a nonpathogen, produced negligible amounts of enzyme. C. albicans CAP production was similar in each protein-supplemented medium, and only a single acid proteinase was recovered from each one. Rapid CAP purification from culture supernatants was achieved by hollow fiber and stirred cell ultrafiltration followed by Affi-Gel blue and Sephacryl column chromatographies. The highest yield, purity, and specific activity of CAP were obtained from keratin-supplemented medium supernatants, producing 2.86 mg of purified CAP from a 7-liter culture. CAP was characterized as a 41,500-dalton glycoprotein, with a pI of 4.5; a pH range of 2.5 to 5.5; and broad substrate specificity, including that for keratin, denatured collagen, hemoglobin, casein, and albumin. Isolation of CAP also isolated the keratinolytic proteinase of Candida spp. CAP was inhibited by pepstatin A, but not by EDTA or phenylmethylsulfonyl fluoride. Monospecific antibody to CAP was produced in mice and reacted only to the 41,500-dalton protein, as determined by immunoblot analysis. High CAP production by cutaneous pathogenic Candida spp. supports the fact that CAP is a potential virulence factor that may facilitate Candida colonization and invasion of skin. CAP production from keratin-supplemented medium was superior to that from the other media that were tested and yielded sufficient and suitable enzyme for use in immunoassays of CAP antigen and antibody.

Animals↗
PubMed1989

Systemic candidiasis.

Systemic candidiasis is a disease of increasing incidence and proportions, which appears to be associated with the advances in modern medicine. It involves primarily patients with severe debilitating and malignant disease who are receiving immunosuppressive, cytotoxic, antimetabolite, and antibiotic therapy. Side effects of these otherwise major therapeutic agents predispose patients to opportunistic fungal infections, of which candidiasis is the most common. The high morbidity and mortality of disseminated candidiasis in neutropenic patients are difficult obstacles to obtaining the optimal, if not full, potential of modern chemotherapy for cancer. The inability to diagnose early invasive and systemic candidiasis is a major handicap that delays timely initiation of antifungal therapy. The paucity of highly efficacious antifungal agents with low toxicity severely limits the ability to successfully cure systemic fungal infections in cancer patients. Aggressive research into the basic biology of Candida spp. is necessary for directing the development of better diagnostic methods and improved antifungal drugs.

Amphotericin B↗
PubMed1988

Scanning electron microscopy of epidermal adherence and cavitation in murine candidiasis: a role for Candida acid proteinase.

Adherence of blastoconidia to epidermal corneocytes is an early event in Candida colonization and infection of the skin. Pathogenic species adhere more avidly than nonpathogenic species, transform to hyphal growth, and invade the stratum corneum of the skin. Adherence was studied by scanning electron microscopy of experimental murine cutaneous Candida infections, using six species of Candida. Candida albicans and C. stellatoidea blastoconidia, applied to newborn mouse skin, adhered to the stratum corneum in greater numbers than other species tested, acquired fibrils and strands of amorphous mucinlike material ("cohesin") between spores and the corneocyte cell surface, formed cavitations in the corneocyte surface, and invaded the corneocyte envelope by hyphal growth at sites distant to the point of blastoconidia attachment. Other species showed little or no adherence, colonization, or cavitation of the corneocyte surface, except C. tropicalis, which showed intermediate results. Pepstatin, an inhibitor of Candida acid proteinase, did not alter adherence or cohesion formation, but inhibited formation of corneocyte cavitations about adherent blastoconidia, suggesting that this enzyme may facilitate adherence/invasion events on skin. Depletion of surface lipids did not alter the formation of cohesin material or the adherence process. Adherence and invasion of epithelium by pathogenic Candida species include the interaction of blastoconidia with an epithelial surface cohesin material that participates in the adherence process. Candida acid proteinase, a keratinolytic enzyme, may participate in the cavitation process of the corneocyte surface by C. albicans.

Animals↗
PubMed1987

Oral candidiasis.

Oral candidiasis is one of the more common infections encountered by man. It manifests itself in a variety of forms, and can arise in any region of the mouth. A generally innocuous and treatable disorder in healthy individuals, it can be the herald of underlying disorders that affect the endocrine or immune systems. In the debilitated or seriously ill, the capacity for seemingly benign oral candidiasis to progress into fulminating fatal infections by hematogenous dissemination must not be ignored. Oral candidiasis in the otherwise healthy patient challenges the physician's ability to identify the contributing factors and associated diseases that predispose to the infection. In the cancer and transplant patient, oral candidiasis is a harbinger of systemic infection, and has become a significant obstacle to successful management of patients with life-threatening diseases. Although several efficacious agents are available for uncomplicated candidiasis, there remains a need for better prophylactic agents to prevent dissemination and better therapeutic agents to treat established infections in immunocompromised patients.

Candidiasis, Oral↗
PubMed1986

Intrauterine herpes simplex infection resembling mechanobullous disease in a newborn infant.

We present a case of transplacentally acquired intrauterine herpes simplex virus infection in a newborn delivered at 36 weeks' gestation by cesarean section because of intrauterine growth retardation and maternal preeclampsia. The mother experienced a single episode of serotype 2 herpes progenitalis at 14 weeks' gestation. At birth the infant manifested clinical findings of herpes simplex virus infection, which resembled epidermolysis bullosa and aplasia cutis congenita. Preexisting cutaneous lesions and intact fetal membranes at delivery strongly support a transplacentally acquired intrauterine herpes simplex virus infection. Repeated Tzanck smears, viral cultures, and immunohistochemical studies of the skin were required to confirm the diagnosis. Intrauterine herpes simplex virus infection is associated with significant morbidity and mortality but responds to antiviral therapy. Therefore this diagnosis must be considered in the neonate born with bullous or eroded skin lesions.

Adult↗
PubMed1979

Purification of a mannan from Candida albicans which activates serum complement.

Candida species activate complement by the alternative pathway, induce leukocyte migration and, when applied epicutaneously, cause epidermal microabscesses of neutrophils in man and experimental animals. Complement activation by C. albicans appears to be a property of the cell wall. To biochemically identify the complement-activating constituent(s) of C. albicans, an ethyleneglycol extract of growth phase blastospores was prepared. Acid hydrolysis and neutral sugar analysis revealed mannose (82%), fucose (7%), and glucose (11%). The soluble, mannose-rich cell wall polysaccharide of C. albicans activates serum complement via the alternative pathway, induces neutrophil chemotaxis and is antigenically reactive with antisera to C. albicans. This constituent exhibits in vitro endotoxin-like activity as measured by Limulus lysate gelation, but is nonpyrogenic in rabbits. The extracts produced precipitin lines in double immunodiffusion studies against serum from patients with invasive candidiasis and rabbit antisera to mycelial and blastospore preparations of C. albicans, but not against normal serum. Thus, pathogenic properties and reactive phenomenon of C. albicans are in part attributable to a cell wall polysaccharide, mannan.

Animals↗
PubMed1978

Experimental cutaneous candidiasis in rodents; II. Role of the stratum corneum barrier and serum complement as a mediator of a protective infalmmatory response.

Of six species of Candida applied epicutaneously to rodents, only C albicans and C stellatoidea penetrate the stratum corneum and produce inflammation. The role of the stratum corneum and produce inflammation. The role of the stratum corneum in experimental murine Candida infections was studied, therefore, by intraepidermal injection of blastospores in mice that received a prior injection of staphylococcal epidermolysin. All six species caused accumulation of neutrophils if placed within an intraepidermal cleft in contact with viable epidermis. The role of serum complement in cutaneous candidiasis was also studied in vivo in rodents depleted of complement with cobra venom factor or deficient in the fifth component of complement. These animals failed to develop neutrophilic inflammatory responses to the six Candida species tested in contrast to control animals. Candida albicans, C stellatoidea, and C tropicalis developed extensive hyphal proliferation with invasion of the entire cutis and subcutis in these animals. The stratum corneum provides an effective barrier to some, but not all Candida species. When this barrier is penetrated, complement mediates an acute neutrophilic pustular response that resticts Candida proliferation and prevents deep invasion of tissue.

Animals↗
PubMed1976

Experimental cutaneous candidiasis in rodents.

Epicutaneous application of viable Candida albicans or Candida stellatoidea under an occlusive dressing resulted in subcorneal microabscesses in newborn rats and mice. Neither heat-killed C. albicans nor occlusion alone resulted in epidermal micropustules. These results were dependent upon the number of organisms applied and the duration of application. Four additional species of Candida tested did not produce epidermal micropustules. The microscopic pathology of the abscesses revealed penetration of the epidermis by Candida pseudohyphae; the tips of the hyphal processes were seen within the pustules when sections were stained by the periodic acid-Schiff method. The resident flora of the newborn mouse or rat was not substantially altered by occlusion with or without C. albicans during the interval tested. The animal model of cutaneous candidiasis with permit greater manipulation and control in investigations of cutaneous candidiasis and the factors influencing neutrophil accumulation in the epidermis.

Animals↗
PubMed1976

Activation of the alternative (properdin) pathway of complement by Candida albicans and related species.

Accumulations of neutrophilic granulocytes within the epidermis and beneath the stratum corneum of the skin are a prominent histologic feature of experimental and clinical candidiasis. The mechanism of cell accumulation was studied by standard chemotactic methods. Suspensions of viable or heat-killed Candida sp caused marked chemotaxis of human neutrophils in fresh serum. Culture supernatants of Candida sp were not chemotactic. Chemotaxis was dependent upon fresh serum, and could be abolished by heating the serum to 56 degress C for 30 min, suggesting that interaction of these organisms with a heat-labile serum factor generated a chemoattractant. Incubation of Candida sp with fresh human serum resulted in the conversion of the third component of complement and properdin factor B, as measured by immunoelectrophoresis. Conversion did not occur in serum chelated with EDTA, or heated to 50 degress C for 30 min (to destroy factor B). Conversion was present in serum chelated with EGTA (to deplete calcium), or genetically deficient in the fourth component of complement. By contrast, the three components of the kinin-forming system (Hageman factor, prekallikrein, high-molecular-weight kininogen) were not activated by Candida sp. We suggest that Candida sp do not release a chemotactic substance but, in the presence of serum, activate the alternative pathway of complement, generating chemotactic factors.

Candida↗