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C Lamarre

Publications and source records attributed to C Lamarre.

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Candida albicans expresses an unusual cytoplasmic manganese-containing superoxide dismutase (SOD3 gene product) upon the entry and during the stationary phase.

We report here that in addition to a cytoplasmic copper-zinc-containing superoxide dismutase (SOD) and a mitochondrial manganese-containing SOD, Candida albicans expresses a third SOD gene (SOD3). The deduced amino acid sequence contains all of the motifs found in previously characterized manganese-containing SODs, except the presence of a mitochondrial transit peptide. Recombinant Sod3p expressed and purified from Escherichia coli is a homotetramer with a subunit mass of 25.4 kDa. Mass absorption spectrometry detected the presence of both iron and manganese in purified Sod3p but, as determined by metal replacement experiments, the enzyme displays activity only when bound to manganese. Overexpression of SOD3 was shown to rescue the hypersensitivity to redox cycling agents of a Saccharomyces cerevisiae mutant lacking the cytoplasmic copper-zinc-containing SOD. Northern blot analyses showed that the transcription of SOD3 is induced neither by the transition from the yeast to the mycelial form of C. albicans nor by drug-induced oxidative stress. In continuous cultures, the expression of SOD3 was strongly stimulated upon the entry and during the stationary phase, concomitantly with the repression of SOD1. We conclude that Sod3p is an atypical cytosolic manganese-containing superoxide dismutase that is involved in the protection of C. albicans against reactive oxygen species during the stationary phase.

Amino Acid Sequence↗

Expression cloning of the Candida albicans CSA1 gene encoding a mycelial surface antigen by sorting of Saccharomyces cerevisiae transformants with monoclonal antibody-coated magnetic beads.

The mycelial surface antigen recognized by monoclonal antibody (mAb) 4E1 has previously been shown to be present predominantly in the terminal third of the hyphal structures in Candida albicans. We report here the expression cloning of the corresponding gene (CSA1 ) by mAb 4E1-coated magnetic beads sorting of Saccharomyces cerevisiae transformants expressing a C. albicans genomic library. The strategy is both highly selective and highly sensitive and provides an additional genetic tool for the cloning and characterization of C. albicans genes encoding surface proteins. CSA1 is an intronless gene encoding a 1203-residue protein composed of repetitive motifs and domains. Northern analysis indicates that CSA1 is preferentially expressed during the mycelial growth phase, although a low level of CSA1 mRNA can be detected in the yeast form. As evidenced by indirect immunofluorescence microscopy with mAb 4E1, Csa1p is not randomly distributed over the surface of yeast cells, but localizes predominantly in the growing buds. This suggests that the distribution of Csa1p may be restricted to sites of cell surface elongation. Both heterozygous and homozygous C. albicans csa1Delta mutants are viable. Upon induction of mycelial growth, the number and size of hyphal structures derived from the mutants are similar to those observed in the parental wild-type strain. The physiological role of Csa1p has yet to be determined. However, the presence in Csa1p of repeated cysteine-rich hydrophobic domains with significant sequence similarity to motifs found in surface proteins (Ag2 and Pth11) from two distantly related fungal pathogens (Coccidioides immitis and Magnaporthe grisea respectively) suggests a common function in host interaction.

Amino Acid Sequence↗

Synoviorthesis with colloidal 32P chromic phosphate for hemophilic arthropathy: clinical follow-up.

Thirty-one synoviortheses were performed in 22 joints of 14 hemophilic patients (aged 12 to 28 years) with chronic synovitis and for whom "conventional treatments" were considered ineffective. Except for patients with inhibitors, conventional treatments included three to six months of adequate prophylactic therapy with the missing coagulation factors, intensive physiotherapy and, when indicated, antiinflammatory agents and orthosis. Colloidal 32P chromic phosphate was injected intraarticularly in doses of 1.0 mCi for knees and of 0.5 mCi for the other joints. Time of follow-up ranged from two to five years. Frequency and importance of bleeding decreased in all patients. Effect on range of motion was best in knees; six of the seven treated improved and one was unchanged. In elbows, flexion-extension was improved in four cases, unchanged in five and decreased in one; pronation-supination was decreased in four cases. Range of motion was not affected in shoulders and ankles except for internal-external rotation which was improved in two of three shoulders treated. The results of 13 synoviortheses in four hemophilic patients with high titer factor VIII inhibitors were comparable to those in hemophiliacs with no inhibitors. However, in three of the four patients synoviorthesis had to be repeated after two to four years for recurrence of synovitis. Extraarticular escape of radioactivity was monitored 62 times for 17 synoviortheses in 12 patients; extraarticular counts never exceeded 4% of the intraarticular counts. Chromosome aberrations were found not to be increased after treatment in the seven patients in whom adequate analysis could be done.

Adolescent↗

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Child Welfare↗