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Biomedical subjects

D Drake

Publications and source records attributed to D Drake.

At least 55 records · Page 3Linked to original sources

Effects of selenium supplementation in cattle on aquatic ecosystems in northern California.

The potential impact on aquatic ecosystems of supplementing the diets of beef cattle with selenium (Se) was studied on 4 northern California ranches. All study sites included an area of concentrated use by cattle that had diets supplemented with Se. In each case, a stream flowed through the site and provided a control sampling area upstream and a treated sampling area downstream. Specimens of water, sediment, algae, aquatic plants, aquatic invertebrates, and fish were analyzed fluorometrically for total Se content. Significant differences in Se concentration were not found between specimens from upstream control areas and those from downstream areas subjected to use by Se-treated cattle. Evidence was not found that Se supplementation in cattle at maximal permitted concentrations caused Se accumulation in associated aquatic ecosystems.

Analysis of Variance↗

Intravascular haemolysis in association with necrotising enterocolitis.

Severe haemolysis is an unusual occurrence in association with necrotising enterocolitis (NEC). Activation of the Thomsen-Friedenreich (T) antigen on the neonatal erythrocytes is proposed as the mechanism. This haemolytic process is precipitated by transfusion with serum-containing blood products, which should therefore be avoided. Once haemolysis has become established the outcome is usually fatal. This report describes the management of four neonates who had established haemolysis complicating severe NEC. T activation was confirmed in two infants, but could not be tested for in the other two. Exchange transfusion abolished the haemolysis in two patients, who survived. Despite reduced use of blood products the other two infants died. We believe that exchange transfusion was essential in the successful management of the infants who survived, and recommend early exchange transfusion when haemolysis complicates NEC.

Antigens, Tumor-Associated, Carbohydrate↗

CHARGE and esophageal atresia.

CHARGE association was diagnosed in 61 infants, 20 of whom died, mainly during the first 2 years of life. Esophageal atresia and/or tracheoesophageal fistula were present in 10 neonates. Axial skeletal anomalies occurred in 7 of the 10, but none had preaxial limb defects typical of the VATER association. All had major cardiac anomalies, predominantly tetralogy of Fallot. The majority of patients had primary repair of the esophagus. The postoperative course was stormy in all patients, with a high incidence of complications and 70% died. The recognition of features of the CHARGE association is important because it has major prognostic and therapeutic implications.

Abnormalities, Multiple↗

Chelating agents inhibit activity and prevent expression of streptococcal glucan-binding lectins.

Several of the cariogenic mutans streptococci produce cell wall-associated glucan-binding lectins (GBLs). The lectins bind alpha-1,6-linked glucans and have no affinity for other polysaccharides or anomeric linkages. When citrate or lactate was included in the growth medium, expression of the activities of the GBLs of Streptococcus cricetus and S. sobrinus was prevented. Furthermore, chelating agents, including citrate, lactate, EDTA, and acetylacetone, were able to reversibly inhibit glucan-induced aggregation of GBL+ streptococci. In addition, the chelating agents prevented sucrose-dependent streptococcal adhesion to glass surfaces and dispersed preformed adherent masses of the streptococci. Neither citrate nor other chelating agents modified the activities of glucosyltransferases. Expression of the lectin could only be achieved by the addition of manganous ion to the growth medium. Chloramphenicol and other metabolic inhibitors prevented synthesis of GBL in cells obtained from manganese-deficient medium and shifted to manganous ion-sufficient medium. The GBL may be a manganoprotein, the manganese of which may be perturbed, but not removed, by chelating agents. During synthesis of the GBL, manganous ion may be required in order for the protein to achieve an active conformation. Citrate or other chelating agents may have promise as anticaries agents.

Bacterial Adhesion↗

Morbidity and mortality in 46 patients with the VACTERL association.

During a 10-year period, 313 infants were treated at the Hospital for Sick Children for esophageal atresia, of whom 46 had features of the VACTERL association. These 46 patients had a mortality rate of 24%, most deaths being caused by cardiovascular abnormalities. Infants weighing less than 2,050 g had a mortality rate of 26%, double that of heavier infants. During the first year of life there was considerable morbidity resulting from the tracheoesophageal abnormalities. Whenever possible primary repair of the esophagus should be performed; however, many patients with VACTERL association had an unusually long gap between the two ends of the esophagus, and repair under tension was associated with a high incidence of complications. Of the 35 survivors, 25 are in a satisfactory, stable condition, but 10 still require treatment necessitating repeated admission to hospital. Anorectal, renal or skeletal anomalies rarely caused death, but, when severe, were associated with a poor quality of life.

Abnormalities, Multiple↗

Transposon Tn7. cis-Acting sequences in transposition and transposition immunity.

We have identified and characterized the cis-acting sequences at the termini of the bacterial transposon Tn7 that are necessary for its transposition. Tn7 participates in two kinds of transposition event: high-frequency transposition to a specific target site (attTn7) and low-frequency transposition to apparently random target sites. Our analyses suggest that the same sequences at the Tn7 ends are required for both transposition events. These sequences differ in length and nucleotide structure: about 150 base-pairs at the left end (Tn7L) and about 70 base-pairs at the right end (Tn7R) are necessary for efficient transposition. We also show that the ends of Tn7 are functionally distinct: a miniTn7 element containing two Tn7R ends is active in transposition but an element containing two Tn7L ends is not. We also report that the presence of Tn7's cis-acting transposition sequences anywhere in a target replicon inhibits subsequent insertion of another copy of Tn7 into either an attTn7 target site or into random target sites. The inhibition to an attTn7 target site is most pronounced when the Tn7 ends are immediately adjacent to attTn7. We also show that the presence of Tn7R's cis-acting transposition sequences in a target replicon is necessary and sufficient to inhibit subsequent Tn7 insertion into the target replicon.

Base Composition↗

Flagella, motility and invasive virulence of Pseudomonas aeruginosa.

The role of motility as a virulence factor in Pseudomonas aeruginosa burn wound sepsis was examined using mutants deficient in the Fla or Mot phenotype. Physiological profiles of parental strains and Fla- and Mot- mutants were similar with respect to antibiograms, O antigen types, growth rates, and proteolytic, exotoxin A and phospholipase activities, providing evidence for isogenicity. Lethality studies using a subcutaneous mouse burn model showed that three Fla- mutants and one Mot- mutant were much less virulent (10(2) to 10(5) times) than the parent wild-type. Topical challenges in the flame burn model showed that a Fla- mutant of strain M-2 was approximately tenfold less virulent. A reduction in virulence, although somewhat less than tenfold, was also observed in the scald burn model for M-2 Fla-, and Mot- strains. Tissue colonization experiments revealed a characteristic, rapidly systemic infection in burned mice challenged with wild-type organisms. Nonmotile mutants similarly proliferated in the burn wound, but the characteristic bacteraemia and systemic invasion were markedly absent. The infection remained localized in the skin wound and the mice survived. The pattern of infection by nonmotile mutants in the colonization studies was very similar to that obtained with Fla+ cells in burned animals passively treated with antiflagellar antibody. These results add substantial support to the concept of motility as a P. aeruginosa virulence factor in invasive infections.

Animals↗

Specificity of the glucan-binding lectin of Streptococcus cricetus.

The specificity of the glucan-binding lectin (GBL) of Streptococcus cricetus AHT was determined. Examination of the kinetics of aggregation of cell suspensions with glucans containing various percentages of alpha-1,6, alpha-1,4, alpha-1,3, and alpha-1,2 anomeric linkages revealed that only glucans with at least 80% alpha-1,6 linkages promoted strong aggregation. Moreover, only linear glucans with molecular weights greater than 5 X 10(5) were capable of causing rapid aggregation of the bacteria. The lectin was observed to be present on S. cricetus strains, on Streptococcus sobrinus, and on several Streptococcus mutants strains. Preincubation of suspensions of S. cricetus AHT with glucan T10 (molecular weight of 10,000) before the addition of high-molecular-weight glucan resulted in competitive inhibition in a concentration-dependent manner. Inhibition was achieved also with isomaltopentaose, isomaltohexaose, and isomaltooctaose, but at higher concentrations than glucan T10. In contrast, no inhibition was observed with maltoheptaose, providing additional evidence for the specificity of GBL. Treatment of suspensions of S. cricetus AHT with trypsin before and after aggregation with high-molecular-weight glucan revealed a substantial level of protection of GBL when in a bound state. Collectively, these results indicated that GBL has an absolute affinity for glucans rich in alpha-1,6 linkages and possesses an active site which recognizes internal sequences and accommodates isomaltosaccharides of at least nine residues. This unusual specificity may contribute to the colonization of S. cricetus, S. sobrinus, and S. mutans in glucan-containing plaque in the oral cavity.

Agglutination↗

Expression of the glucan-binding lectin of Streptococcus cricetus requires manganous ion.

Streptococcus cricetus AHT exhibited a requirement for manganese for growth and expression of the glucan-binding lectin. While low concentrations of manganese (0.1 to 10 microM) were able to support growth, higher concentrations (greater than 100 microM) were required for full expression of the glucan-binding lectin. The manganous-aquo ion may be important in cellular adhesion and accumulation processes in dental plaque.

Bacterial Adhesion↗

Midgut malrotation diagnosed by ultrasound.

Ultrasound was used to demonstrate the abnormal orientation of the mesenteric vessels in six cases of midgut malrotation. Five of these patients were known to have an abnormality of rotation before the ultrasound scan. In one patient malrotation was predicted from the ultrasound scan and confirmed by a barium study and at operation.

Adult↗

Protection against Pseudomonas aeruginosa infection by passive transfer of anti-flagellar serum.

The specificity of adsorbed flagellar antisera for H-antigen was demonstrated in vitro by cross-agglutination assays, motility inhibition, and an ELISA. The specific flagellar antibody was determined to be an IgG. Complete protection against burn wound sepsis was achieved with flagellar antisera. Cross-protection experiments revealed that protection was not only H-antigen dependent, but specific for the flagella antigen type. Antiserum raised against b-type flagella would only protect against homologous bacterial challenge and not against a-type flagellated strains. Results using a-type antisera were consistent, giving protection only against the homologous strain. In contrast, protective capacity was selectively removed from antisera by adsorbing with Fla+ cells. Bacteria colonized the burn wounds of passively protected mice to similar levels as seen in nonprotected animals, but the colonization remained localized and did not result in systemic infection, a pattern similar to infections with motility mutants observed in other studies. Animals rendered neutropenic prior to burning were not protected with flagellar antisera. These data suggested a role for phagocytic cells in protection. Immobilization by flagellar antiserum was observed both by microscopic studies and by inhibition of colony spreading. Antiflagellar antibody is hypothesized as exerting its protective capacity possibly in two ways; first by inhibiting the motility of invading bacteria by binding to the flagellum and immobilizing the bacteria, and secondly by acting as an opsonin, targeting either immobilized or mobile cells for phagocytosis.

Animals↗

Electrophoretic separation and molecular weight characterization of Pseudomonas aeruginosa H-antigen flagellins.

We found that preparations of Pseudomonas aeruginosa flagellar antigens protected against P. aeruginosa challenge in a burned-mouse model. To determine the extent of similarity among known flagellar antigen types, we compared flagellins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A majority of our laboratory strains and clinical isolates, including PAO strains and their derivative mutants RM46 and PJ108, as well as virulent strains M-2 and 1244, had flagellins of 53,000 Mr. These flagellins had the same Mrs as those of type b-standard strains 170001 and 15084. The heterogeneous group of a-type H-antigen flagellins were of smaller molecular weights, ranging from 52,000 Mr for standard strain 5939 (a0, a3) to 45,000 Mr for standard strain 170018 (a0, a3, a4). Standard strains 5933 (a0, a1, a2) and 5940 (a0, a2) had intermediate Mrs of 51,000 and 47,000, respectively. Differences in Mr of 1,000 to 2,000 could be resolved by coelectrophoresis. A series of 26 unknown strains were categorized. Correlations among typing by molecular weight, cross-agglutination reactions with O-adsorbed H antisera, and previous results for H-serum typing are reported.

Animals↗