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Biomedical subjects

E S Jacobson

Publications and source records attributed to E S Jacobson.

At least 37 records · Page 2Linked to original sources
PubMed1992

Surgical management of perilymphatic fistulas: a Portland experience.

A comprehensive review of our series of surgical perilymphatic fistula (PLF) repairs, as well as a review of published results from other otologists, suggested an unacceptably high rate of postoperative PLF recurrence. Some recurrences were related to specific events (i.e., coughing, strenuous activity, Valsalva-type maneuvers). However many cases had no apparent cause. Rather, the patients' symptoms recurred spontaneously, and at reoperation the graft was seen to have not "taken," suggesting graft failure rather than "patient failure." After a critical evaluation of current PLF surgical procedures and state-of-the-art concepts of wound healing, we developed a new surgical technique for PLF closure. Combining the use of laser graft-site preparation, an autologous fibrin glue "buttress," and a program of postoperative activity restriction, the new procedure allowed us to achieve statistically significant improvements in graft retention and surgical outcome, with recurrences dropping from 27 percent to 8 percent. In addition, complete resolution or significant symptomatic improvement occurred in 89 percent of patients with vertigo and/or dizziness and in 84 percent with disequilibrium. We conclude that this new surgical technique is an important addition to the otologic surgeon's arsenal for PLF management.

Adolescent↗
PubMed1991

Surgical management of perilymph fistulas. A new technique.

A wide range of recurrence rates (21% to 47%) for perilymph fistula repairs have been reported in the otology literature. An improved surgical technique developed at the Portland (Ore) Good Samaritan Hospital and Medical Center Neurotology Department was used to repair perilymph fistulas in 58 patients from October 1986 to October 1988. Our recurrence rate was reduced from 27% in a 1982-1985 study to 8% in our study. At 1 year postoperatively, improvements in disequillibrium, dizziness, and vertigo were comparable with results of older surgical techniques. Functional outcomes were also good: 83% of patients returned to normal activities of daily living, and 71% also returned to school or resumed gainful employment outside the home.

Adolescent↗
PubMed1991

Temperature regulation of the cryptococcal phenoloxidase.

Melanin formation at 37 degrees C has been proposed as a virulence factor in Cryptococcus neoformans. However, whereas catecholamine uptake is maintained at this temperature, phenoloxidase, which catalyses the oxidation of catecholamine to melanin, is severely decreased in most wild type strains cultivated at 37 degrees C.

Catecholamines↗
PubMed1991

Catecholamine uptake, melanization, and oxygen toxicity in Cryptococcus neoformans.

Oxygen sensitivity mutations of Cryptococcus neoformans were mapped to three genetic loci. Three oxygen-sensitive mutants had mutations that appeared allelic and exhibited albinism tightly linked to oxygen sensitivity; these three and a fourth exhibited defects in catechol uptake and catechol oxidation to melanin. Catecholamine metabolism appears to protect C. neoformans from oxidants.

Biological Transport↗
PubMed1990

Side group addition by xylosyltransferase and glucuronyltransferase in biosynthesis of capsular polysaccharide in Cryptococcus neoformans.

The capsular polysaccharide of Cryptococcus neoformans consists of an O-acetylated mannan backbone with xylosyl and glucuronyl substituents. We have studied two enzymes in the biosynthetic pathway of this polysaccharide. A particulate enzyme preparation contained xylosyltransferase and glucuronyltransferase activities with pH optima of 7.5 and less than 6.5, and optimum incubation temperatures of 25 degrees and 37 degrees C respectively. O-acetylated mannan served as an acceptor for glucuronyl residues but xylomannan did not. Glucuronomannan served as an acceptor for xylosyl residues but acetylated mannan did not. These observations suggest that glucuronate is added before xylose and after acetate. This hypothesis was supported by studies of lipid-linked sugars in which a microsomal preparation was incubated with various combinations of nucleotide sugars. With GDP-mannose, UDP-glucuronate and UDP-[14C]xylose; GDP-mannose, UDP-[14C]glucuronate and UDP-xylose; or GDP-mannose and UDP-[14C]glucuronate, no evidence for a lipid-linked monosaccharide was obtained. However, lipid-linked xylose was detected only if GDP-mannose and UDP-[14C]xylose were provided, a finding consistent with a pool of lipid-linked xylose which is only transferred following glucuronylation. The order of addition inferred is mannosyl, acetyl, glucuronyl and xylosyl.

Carbohydrate Sequence↗
PubMed1989

Effect of hypertonic solutes upon the polysaccharide capsule in Cryptococcus neoformans.

The polysaccharide capsule is a characteristic virulence factor in the yeast-pathogen, Cryptococcus neoformans. Growth in hypertonic growth media results in yeast cells with visibly smaller capsules. We investigated this suppression quantitatively, using a chemical assay for cell-bound and dissolved capsular polysaccharide. Molar NaCl suppressed production of cell-bound polysaccharide by a factor of 2.5- to 5-fold. The possibility of salt-induced physico-chemical contraction of capsular gel was tested by dialysis of fixed cells from hypotonic medium against medium containing 1 M NaCl and against the original medium again, while capsular thickness, packed cell volume and cell-bound polysaccharide were followed. We detected a physical contraction of gel following dialysis against medium containing 1 M NaCl. Mutants which gave mucoid colonies on hypertonic agar were isolated. One of these gave twice as much polysaccharide as the wild type when cultivated in medium containing 1 M NaCl. The hypercapsular trait was passed through serial outcrosses to the wild type and segregated as a chromosomal gene. This mutant may represent a gene which regulates production of capsular polysaccharide.

Cryptococcus↗
PubMed1989

Localization of mannoprotein in Cryptococcus neoformans.

Cell wall mannoprotein of nonpathogenic yeasts is surface exposed, since the cells are agglutinated by concanavalin A and antimannoprotein antibodies. However, nonencapsulated cells of Cryptococcus neoformans were agglutinated neither by concanavalin A nor by antimannoprotein antibodies. Immunogold electron microscopy located most mannoprotein in the inner cell wall. Chemical analysis of purified cell walls showed the lack of mannose, xylose, and galactose residues. These data indicate that cryptococcal mannoprotein recovered from the cultural supernatant is a nonstructural element of the cell wall.

Cell Wall↗
PubMed1987

Cryptococcal UDP-glucose dehydrogenase: enzymic control of capsular biosynthesis.

UDP-Glucuronate, formed through dehydrogenation of UDP-glucose and itself decarboxylated to make UDP-xylose, is the presumed donor for the glucuronyl side-groups in biosynthesis of the capsular polysaccharide in Cryptococcus neoformans. A specific radiochromatographic assay for UDP-glucose dehydrogenase shows that the enzyme is present in the cytosol. The enzyme is very labile but is stabilized by 25% glycerol. The enzyme is inhibited strongly by NADH (Ki,NADH = Km,NAD = 0.1 to 0.2 mM). It is also inhibited competitively by UDP-xylose (Ki = 0.3 mM). These results suggest that the rate of production of the capsular precursor, UDP-glucuronate, is controlled by the intracellular concentrations of an end product, UDP-xylose, and of a direct product, NADH. Capsule mutants have been screened for activity of this enzyme but none is clearly deficient.

Carbohydrate Dehydrogenases↗
PubMed1987

Extracellular iron chelation in Cryptococcus neoformans.

Low-iron minimal medium supported growth of Cryptococcus neoformans but spent medium contained no hydroxamates, organic acids or other iron chelators. Exogenous deferoxamine stimulated growth in extreme iron-limitation, while neither organic acids nor quartersaturated transferrins were stimulatory. These results suggest two iron uptake mechanisms, one dependent upon exogenous hydroxamate, the other hydroxamate-independent.

Cryptococcus↗
PubMed1985

Occurrence of diploid strains of Cryptococcus neoformans.

A mating between niacin and pantothenate auxotrophs of Cryptococcus neoformans gave a few prototrophic progeny that were self-fertile. These were uninuclear but contained twice as much DNA as the parental strains. Segregation of nutritional markers was observed upon sporulation. We conclude that these self-fertile strains are diploids.

Cryptococcus↗
PubMed1985

Cytologic identification of trophoblastic epithelium in products of first-trimester abortion.

A cytologic method is described for the identification of trophoblastic epithelium in products of first-trimester abortion. In material from 50 consecutive induced first-trimester abortions, trophoblast was identified cytologically in 46 cellular samples (93.9%). In addition, nucleated fetal erythrocytes were found in 26 cellular samples (53%). There were no false positives, and three false negatives occurred. One negative examination, confirmed by histologic study, led to procedures that diagnosed ectopic tubal pregnancy. The cytologic method is easily performed and is rapid, sensitive, certain, inexpensive, and permanent. Cytologic study should not supplant meticulous macroscopic examination of abortion products by the clinician.

Abortion, Induced↗
PubMed1982

Decreased virulence in stable, acapsular mutants of cryptococcus neoformans.

Six acapsular strains of Cryptococcus neoformans obtained by chemical mutagenesis failed to produce a capsule in vivo and were avirulent in mice following high dose intramuscular, intraperitoneal or intravenous inoculation. Peritoneal granulomas were observed in all animals inoculated with the acapsular mutants. These granulomas were characterized by a large central mass consisting of intact, degenerating and necrotic yeast cells. This was surrounded by concentric layers of a broad band of histiocytes, a narrow band of fibroblasts, and around the periphery, a mass of lymphocytes and plasma cells. These isolates did not revert to an encapsulated or virulent state after more than a year of subculturing or 18 passages through mice.

Animals↗
PubMed1982

Cysteine-independent and cysteine-requiring yeast-strains of Histoplasma capsulatum.

Recently we described a strain of Histoplasma capsulatum, designated H-35, which is able to grow as yeast on a minimal medium consisting of inorganic salts, glucose and a trace of biotin. Using this strain as a prototrophic wild type we sought auxotrophic mutants. Mutagenized yeast-cells were starved for inorganic sulfate in sulfur-free minimal medium. Sulfate was then added, and growing prototrophic cells were killed by addition of amphotericin B. After 24 hours non-growing auxotrophs were 'rescued' by removal of amphotericin and addition of yeast extract. This 'mutant enrichment' cycle was repeated two additional times, after which the cells were plated on blood agar and 800 yeast-colonies were picked. Seventeen of these yeast-strains required cysteine for growth, as compared with strain H-35, which grew as yeast on minimal medium.

Amphotericin B↗
PubMed1982

Genetic and phenotypic characterization of capsule mutants of Cryptococcus neoformans.

Stable mutants with reduced capacity to produce capsules were isolated from suspensions of Cryptococcus neoformans after treatment of the wild type with a mutagen. The mutants could be assigned one of two phenotypes, hypocapsular or acapsular. Hypocapsular mutants were immunochemically and physicochemically indistinguishable from the wild type, whereas acapsular mutants lacked a major capsular antigen and a negatively charged exterior. In genetic analysis, the mutant trait segregated as a Mendelian gene (1:1) when random basidiospores from an outcross were studied, and analysis of products of single meiotic events from outcrossed mutants was likewise consistent with meiotic segregation. Two-factor crosses yielded the expected four classes of progeny, with recombinants equal to parentals. We concluded that chromosomal genes are responsible for synthesis of the cryptococcal capsule and that random basidiospore analysis represents a useful technique for genetic analysis in this species.

Antigens, Fungal↗