Search PubMed⌕ Search

Biomedical subjects

F E Young

Publications and source records attributed to F E Young.

158 records · Page 9Linked to original sources
PubMedDate not supplied

New shuttle vectors for Bacillus subtilis and Escherichia coli which allow rapid detection of inserted fragments.

Two new shuttle vectors have been constructed by fusing the Escherichia coli plasmid pUC9 with the Staphylococcus aureus plasmids pU110 and pC194. The resulting hybrids replicate in both E. coli and Bacillus subtilis and contain seven restriction sites within a part of the lacZ gene. Insertion of foreign DNA into those sites can be easily detected in E. coli and hybrid plasmids can subsequently be transformed into B. subtilis.

Bacillus subtilis↗
PubMedDate not supplied

Cloning and mapping of the dihydrofolate reductase gene of Bacillus subtilis.

The structural gene for dihydrofolate reductase (dfrA) from the Bacillus subtilis 168 chromosome has been cloned, along with the thyB gene, on a 4.5-kb insert contained on chimeric plasmid pER1. The presence of the dfrA gene on pER1 was demonstrated by showing that: (i) transformation of Escherichia coli strains RUE10(Thy-) and RUE11(Thy+) with pER1 resulted in a 60 to 130-fold increase in dihydrofolate reductase (DFRase) activity with a turnover number characteristic of that of B. subtilis and (ii) pER1-mediated transformation of trimethoprim-resistant E. coli strain D05, which overproduced a DFRase with a decreased affinity for trimethoprim, resulted in a 41-fold increase in DFRase activity with an affinity for trimethoprim similar to that of the B. subtilis enzyme. The dfrA gene was mapped to the 200 degrees region of the B. subtilis chromosome, and the gene order was established as thyB dfrA ilvA. Furthermore, the dfrA gene was shown to be linked closely (95-99% cotransformation) to the thyB gene.

Bacillus subtilis↗
PubMedDate not supplied

Genetic determinants of microbial resistance to antibiotics.

Emergence of antibiotic resistance is related to the ease of mutation, to the extent of exchange of genetic information in bacteria by conjugation, transformation, and transduction, and to the large-scale use of antimicrobial agents in the biosphere. In addition to the development of resistance through chromosomal mutation and exchange of chromosomal genes among organisms, there is a more profound enlargement of the gene pool by the dissemination and amplification of plasmids. Two examples of the exchange of antibiotic resistance are analyzed: the transfer of plasmids from Bacteroides fragilis to Escherichia coli and the emergence of antibiotic-resistant strains of STreptococcus pneumoniae. Plasmids encoding antibiotic resistance in B. fragilis were transferred to E. coli by DNA-mediated transformation and conjugation. The beta-lactamase in the transformants and transconjugants displayed the same substrate specificity and electrophoretic mobility as the donor strain. The plasmid apparently was integrated rapidly into the chromosome of the recipient strain. Multiple antibiotic-resistant strains of S. pneumoniae were analyzed for plasmids, and none were detected. Furthermore, no evidence of linkage between the traits of multiple antibiotic resistance was observed. beta-Lactamase was not detected in the penicillin-resistant strains; therefore, it is likely that the resistance in these strains was chromosomal rather than plasmid-mediated. The range of genetic exchange and the use of Koch's postulates in determining the genetic mechanism of antibiotic resistance are illustrated and discussed.

Bacteria↗
PubMedDate not supplied

Auxotypes and antibiotic susceptibility patterns of Neisseria gonorrhoeae from disseminated and local infections.

The arginine-hypoxanthine-uracil auxotype has been linked with the propensity of gonococci to cause disseminated infections. Gonococci recovered from 25 patients with disseminated gonococcal infections were compared with gonococci recovered from matched controls, patients with uncomplicated gonorrhea selected during the same month. Minimal inhibitory concentrations of penicillin, tetracycline, erythromycin, and ampicillin, and the nutritional requirements (auxotypes) for proline alone, arginine alone, arginine, hypoxanthine and uracil together, serine alone and cysteine-cystine (wild type) were analyzed by discriminant analysis. Significant susceptibility to penicillin characterized strains causing disseminated infection, and a proline requirement was the most common auxotype (48%) among strains isolated in Atlanta. Together the minimal inhibitory concentration of penicillin and the proline auxotype best separated the strains causing gonorrhea. The arginine-hypoxanthine-uracil auxotype was was found in only 24% of strains causing disseminated infections. A trait other than auxotype must determine the capacity of the organisms to disseminate.

Adult↗
PubMedDate not supplied

Inhibition of active transport and macromolecular synthesis by pyocin 103 in Neisseria gonorrhoeae.

The mechanism of inhibition of Neisseria gonorrhoeae by pyocin 103 was examined. Pyocin 103 decreases the viability of N. gonorrhoeae immediately after its addition to logarithmically growing cells by single-hit kinetics. This inhibition was paralleled by an immediate cessation of protein synthesis, RNA synthesis, and active transport. From the data presented, it is likely that pyocin kills N. gonorrhoeae in the same manner that it kills Pseudomonas aeruginosa, i.e., by interfering with energy metabolism.

Bacterial Proteins↗
PubMedDate not supplied

Construction and characterization of chimeric beta-lactamase plasmids of Neisseria gonorrhoeae with altered ability to be mobilized during conjugation.

A series of chimeric plasmids derived from the transfer factor, beta-lactamase-encoding R factor, and cryptic plasmid of Neisseria gonorrhoeae was constructed. Two of these plasmids, each lacking a 1.9-kilobase-pair (kb) HinfI fragment, could not be mobilized by the 40-kb gonococcal transfer factor to recipient strains of N. gonorrhoeae or Escherichia coli during conjugation. The proteins encoded by both the naturally occurring and chimeric plasmids were examined with an E. coli cell-free transcription-translation system and in E. coli maxicells. Six plasmid-specific proteins were identified when DNA from a naturally occurring 7.1-kb R factor was used as template. A small protein (16,000 daltons), which is apparently not encoded by the two plasmids lacking the 1.9-kb HinfI fragment, appears to be necessary for plasmid transfer during conjugation.

Bacterial Proteins↗
PubMedDate not supplied

The role of the FDA in the effort against AIDS.

The Food and Drug Administration has instituted several pro-active measures to expedite the review of treatments, diagnostics, and vaccines for AIDS and related conditions. In particular, the agency has established a special designation--1-AA--for a potential AIDS product which gives top priority to its review. This special expedited review process for AIDS products has provided for greater cooperation between their sponsors and FDA's reviewers. AIDS products also receive prompt consideration for orphan product status--a status providing financial incentives to the developers of treatments for certain rare and complex diseases. FDA's special procedures for AIDS drugs have resulted in several major advances in available AIDS treatments. Foremost among these was the FDA's review and approval of zidovudine (commonly known as AZT) as the first effective palliative for AIDS within 107 days--an agency record. Similarly, the agency quickly evaluated and approved ELISA and Western blot diagnostic kits for detecting the presence of HIV antibody. These test kits have made an important contribution to safeguarding the nation's blood supply. The agency has also instituted new "treatment" investigational new drug regulations to allow earlier pre-approval distribution of promising experimental treatments to patients with immediately life-threatening conditions, including persons with AIDS. Under this system and its earlier prototype, eligible AIDS patients were able to receive pre-approval treatment with zidovudine and trimetrexate (an experimental drug for the treatment of AIDS patients with Pneumocystis carinii pneumonia who have experienced severe adverse reactions using standard approved therapies). The agency has made institutional reforms to effectively streamline the review of candidate AIDS treatments and vaccines. Two new centers within the agency have been established for the processing of drug and biologics. In addition,reviewing divisions have been created within these centers to give specialized attention to drugs and biologics designed to treat AIDS or related conditions.These efforts and the other aforementioned reforms, in part, have lead to the initiation of more than 100 ongoing clinical studies of potential drugs for AIDS and related conditions, as well as the clinical testing of two candidate vaccines against HIV. In other areas, FDA has increased inspections of the manufacturing and processing of condoms and begun a surveillance and sampling program to insure the quality of latex surgical gloves. The agency has worked with other authorities to move against quack AIDS products and to educate the public concerning this health fraud.FDA hopes that through all these efforts it can help researchers in government, academia, and industry advance the development, testing, and review of safe and effective therapies, preventatives,and diagnostics for AIDS and related conditions.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Marketing approval for the lithotripter.

In December 1984, the Food and Drug Administration (FDA) granted Dornier Systems (FRG) approval to market the external shock wave lithotripter (ESWL) in the USA. The Medical Device Amendments of the Food, Drug, and Cosmetic Act require that the FDA evaluate the safety and effectiveness of medical devices intended for commercial distribution in the U.S. Such evaluation includes basic scientific studies, animal testing, and investigational studies in human subjects, culminating in a judgment concerning acceptable risks in terms of anticipated benefits, and whether the device is effective for its intended use. Prior to human studies in West Germany, Dornier had evaluated the destruction of stones of varying composition, measured the rate and energy of stone destruction, and tested blood samples and lymphocyte cultures exposed to shock waves. In addition, studies in both rats and dogs had demonstrated the feasibility of the technique and evidence of safety. Such data are provided by manufacturers when applying for an investigational device exemption (IDE) from the FDA, which permits clinical studies in humans; such studies also require the approval of an Institutional Review Board. The FDA approved Dornier's IDE, allowing human investigational use of the ESWL in facilities in the U.S., conducted concurrently with similar studies in West Germany. Upon completion of clinical trials, data acquired in vitro, in laboratory animals, and in human investigations are submitted to the FDA for a premarked approval application (PMAA). The Agency was given 6 months to make a decision, taking into consideration the recommendation of an advisory panel of experts from outside the Agency who had reviewed the same data. In its evaluation of the ESWL for safety and effectiveness, the FDA considered the question of alternative practices and procedures to treat nephrolithiasis, including percutaneous nephrolithotomy and open surgical procedures, and the adverse effects of such procedures. Clinical data available at the time of review for approval included reports of treatment of 667 patients in West German centers, and 327 patients treated in three U.S. facilities. Dornier and the FDA initiated discussions concerning the labeling of the device and a postmarketing surveillance plan. These were completed and marketing approval for the ESWL was granted.

Costs and Cost Analysis↗