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Biomedical subjects

G Peter

Publications and source records attributed to G Peter.

At least 19 recordsLinked to original sources

The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.

Arabidopsis↗

Gene expression during formation of earlywood and latewood in loblolly pine: expression profiles of 350 genes.

The natural variability of wood formation in trees affords opportunities to correlate transcript profiles with the resulting wood properties. We have used cDNA microarrays to study transcript abundance in developing secondary xylem of loblolly pine (Pinus taeda) over a growing season. The cDNAs were selected from a collection of 75 000 ESTs that have been sequenced and annotated (http://web.ahc.umn.edu/biodata/nsfpine/). Cell wall thickness and climatic data were related to earlywood and latewood formation at different time points during the growing season. Seventy-one ESTs showed preferential expression in earlywood or latewood, including 23 genes with no significant similarity to genes in GenBank. Seven genes involved in lignin synthesis were preferentially expressed in latewood. The studies have provided initial insights into the variation of expression patterns of some of the genes related to the wood formation process.

Expressed Sequence Tags↗

Improving loblolly pine somatic embryo maturation: comparison of somatic and zygotic embryo morphology, germination, and gene expression.

Clonal production of loblolly pine ( Pinus taeda L.) through somatic embryogenesis has the potential to meet the increasing industrial demands for high-quality uniform raw materials. A major barrier to the commercialization of this technology is the low quality of the resulting embryos. Twenty-five newly initiated loblolly pine genotypes were followed through the process of liquid culture establishment, embryo maturation, germination, and retrieval from cryogenic storage. A maturation medium, capable of promoting the development of loblolly pine somatic embryos that can germinate, is presented that combines 1/2 P6 modified salts, 2% maltose, 13% polyethylene glycol 8000 (PEG), 5 mg/l abscisic acid (ABA), and 2.5 g/l Gelrite. A procedure for converting and acclimating germinants to growth in soil and greenhouse conditions is also described. A set of somatic seedlings, produced from the maturation medium, showed 100% survival when planted in a field setting. Somatic seedlings showed normal yearly growth relative to standard seedlings from natural seed. The quality of the resulting embryos was examined and compared to that of zygotic embryos using such parameters as morphology, dry weight, germination performance, and gene expression. All of the observations that were made support the conclusion that even with the new maturation medium somatic embryos grow approximately only halfway through the normal sequence of development and then prematurely discontinue growth.

Abscisic Acid↗

Recommended schedules for routine immunization of children and adults.

Vaccine recommendations continue to evolve as a result of new vaccines, safety considerations, changing disease incidence (e.g., polio), and public health priorities. The pace of discovery is accelerating and advisory committees will need to respond accordingly. Each vaccine, new or old, will be required to earn its place in the routine immunization schedule on the basis of public health benefit or cost-benefit studies.

Adult↗

Standards for immunization practice for vaccines in children and adults.

Administration of vaccines is a continuing challenge. In childhood immunizations, many of the goals for national coverage rates by 2000 were achieved and the goal of annual influenza immunization for adults 65 years of age and older was reached. These successes in childhood immunization rates have led to record low numbers of cases of many vaccine-preventable diseases, such as measles and Haemophilus influenzae, type b invasive disease. These diseases will recur, however, as evidenced by the measles epidemic of 1989-1991, if high immunization coverage is not maintained. The development of immunization delivery systems to sustain these high rates in young children is essential to ensure that the 11,000 infants born each day in the United States receive all recommended vaccines, as noted in the recent NVAC report on strategies to sustain success in childhood immunization. For adults, the total economic burden of treating these vaccine-preventable diseases is estimated to exceed $10 billion each year, reflecting in part widespread underuse of vaccines in adults and resulting missed opportunities to prevent diseases such as influenza and pneumococcal infection. The development of standards for immunization practices in children and adults has been an important component in meeting these challenges and ensuring appropriate delivery of vaccines. Periodic review and updating is necessary and revision of the standards for adults by the NCAI and NVAC, pediatric standards, and those of the IDSA currently are undergoing revision. Most importantly, however, standards for immunization practices should be promulgated widely to all health care professionals to ensure that all segments of the population benefit from the availability of highly effective and safe vaccines.

Adult↗

An analysis of the immunization status of preschool children enrolled in a statewide Medicaid managed care program.

OBJECTIVES: To measure immunization coverage rates for children enrolled in a statewide Medicaid managed care program and determine the impact of sociodemographic characteristics and the type of primary care provider site on immunization coverage. STUDY DESIGN: A random sample of 2000 was chosen from children between the ages of 19 and 35 months who had been continuously enrolled in the Medicaid managed care program for 1 year. Sociodemographic data and a list of primary care providers for the study children were obtained from administrative databases. Immunization histories were determined by medical record review. RESULTS: Vaccine-specific immunization rates for diphtheria-tetanus-pertussis, polio, Haemophilus influenzae type b, hepatitis B, and measles-mumps-rubella ranged from 87% to 94%, with an overall coverage rate of 75%. Overall immunization status varied by primary care provider site as follows: office-based, 72%; community health center, 75%; hospital-based clinic, 79%; and staff model health maintenance organization, 85% (chi(2) test, P =.008). CONCLUSIONS: Immunization rates compare favorably with national rates for this low-income group. Sociodemographic characteristics were not important predictors of underimmunization, but rates did vary by the type of primary care provider site.

Child Health Services↗

New metabolic pathways of alpha-lipoic acid.

The excretion and biotransformation of rac-alpha-lipoic acid (LA), which is used for the symptomatic treatment of diabetic polyneuropathy, were investigated following single oral dosing of [(14)C]LA to mice (30 mg/kg), rats (30 mg/kg), dogs (10 mg/kg), and unlabeled LA to humans (600 mg). More than 80% of the radioactivity given was renally excreted. Metabolite profiles obtained by radiometric high-performance liquid chromatography revealed that LA was extensively metabolized irrespective of the species. Based on a new on-line liquid chromatography/tandem mass spectroscopy assay developed for negative ions, LA and a total of 12 metabolites were identified. Mitochondrial beta-oxidation played the paramount role in the metabolism of LA. Simultaneously, the circulating metabolites were subjected to reduction of the 1,2-dithiolane ring and subsequent S-methylation. In addition, evidence is given for the first time that the methyl sulfides formed were partly oxidized to give sulfoxides, predominantly in dogs. The disulfoxide of 2,4-bismethylmercapto-butanoic acid, the most polar metabolite identified, was the major metabolite in dogs. Furthermore, new data are presented that suggest conjugation with glycine occurred as a separate metabolic pathway in competition with beta-oxidation, predominantly in mice.

Animals↗

The effect of troglitazone biliary excretion on metabolite distribution and cholestasis in transporter-deficient rats.

We investigated whether lack of the canalicular multispecific organic anion transporter in transport-deficient (TR-) rats would result in plasma and urinary accumulation of troglitazone or its major metabolites and whether any accumulation would be associated with increased levels of bilirubin or bile acids. Administration of a single oral dose of troglitazone (200 mg/kg) to TR- rats resulted in 2- and 50-fold increases in plasma levels and 30- and 500-fold increases in urinary amounts of troglitazone sulfate and troglitazone glucuronide, respectively, compared with normal rats. No changes were found in the plasma concentrations and urinary amounts of troglitazone or troglitazone-quinone. Accumulation of troglitazone metabolites in plasma was accompanied by a 2-fold increase in the serum level of conjugated bilirubin in TR- rats, whereas no changes were observed in normal animals. Bile acids were detected in the urine of both TR- and normal rats, with an average 3-fold greater level found in the urine of TR- animals. Biliary metabolic profiles revealed a delay in the secretion of troglitazone sulfate and troglitazone glucuronide in TR- rats over the first 2- and 4-h periods, respectively. These results demonstrate the role of multidrug resistant associated protein-2 in biliary secretion of troglitazone glucuronide and troglitazone sulfate and suggest the presence of compensatory mechanisms responsible for transport of troglitazone metabolites and bilirubin-glucuronide at the basolateral and canalicular sites of hepatocytes.

Animals↗

The impact of outreach efforts in reaching underimmunized children in a Medicaid managed care practice.

BACKGROUND: National immunization standards call for all primary care providers to implement immunization tracking systems that include contacting families when children are overdue for vaccines. The restructuring of Medicaid systems toward managed care models with a greater emphasis on having defined medical homes for children presents opportunities to expand the use of immunization recall systems among low-income children. OBJECTIVE: To assess the impact of telephone, mail, and a combined approach to reaching underimmunized children enrolled in a hospital-based Medicaid managed care practice. DESIGN AND METHODS: All underimmunized children younger than 6 years who had been continuously enrolled in the hospital-based Medicaid managed care practice for 3 months were randomly assigned to 1 of 4 groups: (1) control group with no intervention, (2) telephone reminder group, (3) mail reminder group, or (4) sequential mail/telephone reminder group. After a 10-week follow-up, medical records and the hospital's computerized appointment scheduling system were reviewed to determine the effect of the outreach effort on appointments made, visits attended, immunizations received, and immunization status. RESULTS: Outreach efforts had a positive impact on the proportion of children immunized and on the resulting immunization coverage rates. The percentage of children receiving immunizations during the 10-week follow-up was 4.2% (3/71) for the control group, 16.7% (10/60) for the telephone reminder group, 19.0% (12/63) for the mail reminder group, and 25.7% (18/70) for the sequential mail/telephone reminder group. The percentage of children up-to-date for all immunizations at the end of the 10-week follow-up was 2.8% (2/71) for the control group, 13.3% (8/60) for the telephone reminder group, 14.3% (9/63) for the mail reminder group, and 17.1% (12/70) for the sequential mail/telephone reminder group. Forty-eight children were seen during follow-up without receiving all indicated vaccines. CONCLUSIONS: Outreach efforts were modestly successful in reaching underimmunized children in a Medicaid managed care practice, although the lack of accurate information on telephone numbers and addresses limited the effectiveness. Missed opportunities for immunization also reduced the impact of outreach on immunization coverage. Arch Pediatr Adolesc Med. 2000;154:1243-1247.

Child↗

A high degree of natural immunologic priming to the capsular polysaccharide may not prevent Haemophilus influenzae type b meningitis.

BACKGROUND: A current debate is whether the immunologic priming of infants with Haemophilus influenzae type b (Hib) conjugate vaccines would be protective in the absence of circulating antibody to the capsular polysaccharide (PS). Data from the prevaccine era on the PS antibody responses of older children to Hib meningitis may be informative on this issue. METHODS: PS antibody was assayed by radioantigen binding in sera taken in the first month postadmission in 47 children ages 2 to 136 months with culture-proved Hib meningitis. RESULTS: Sera obtained on admission had very low antibody concentrations, and the subsequent response during convalescence was age-dependent. The major finding is that some patients, including 10 of 11 children older than 2 years, had substantial antibody elevations within a few days of admission, increases resembling the response to PS vaccine in infants primed with PS-protein conjugate vaccines. CONCLUSIONS: In this group of patients with Hib meningitis, natural priming did not prevent infection. Hib may have the ability to invade despite the capacity for a vigorous antibody response.

Age Factors↗

Disposition and metabolism of cetrorelix, a potent luteinizing hormone-releasing hormone antagonist, in rats and dogs.

Disposition and metabolism of cetrorelix was studied in intact and bile duct-cannulated rats and dogs after s.c. injection. An s.c. dose of 0.1 mg/kg [(14)C]cetrorelix was rapidly and completely absorbed in rats. T(max) in plasma and most tissues was at 2 h. Radioactivity at the injection site in rats declined to 10% by 24 h. The extent of (14)C absorption in rats calculated from excretion until 264 h was 94%. Exposure of the target organ pituitary gland was demonstrated with a time course similar to plasma but on a higher level. Rats excreted 69.6% of radioactivity via feces and 24. 3% into urine. Excretion was nearly complete within 48 h. No enteral reabsorption was detected. In dogs t(max) in plasma was 1.3 h. (14)C- and cetrorelix-plasma levels were similar until 24 h, indicating a negligible amount of metabolites. A dose of 1 mg/kg in dogs showed an increasing influence of a slow absorption phase (flip-flop). In dogs equal amounts of the (14)C dose were found within 192 h in feces and urine, 46 and 48%, respectively. In urine of both species, only intact cetrorelix was detected. In bile and feces of both species qualitatively the same metabolites were found, characterized as truncated peptides of the parent decapeptide. The major metabolite occurring in bile of both species was the (1-7)heptapeptide. The amounts of the (1-4)tetrapeptide in feces of rats but not in that of dogs increase with time, suggesting additional degradation of the peptide in the gastrointestinal tract of rats by enteric metabolization.

Absorption↗

Immunization status of children enrolled in a hospital-based medicaid managed care practice: the importance of the timing of vaccine administration.

OBJECTIVES: To evaluate the immunization status of children enrolled in a hospital-based Medicaid managed care practice and to assess the impact of the timing of vaccine administration on measured immunization rates. DESIGN AND METHODS: The medical records of all children between the ages of 19 and 35 months who were continuously enrolled in the Medicaid managed care practice for the last 6 months of 1996 were reviewed. Immunization status was determined for the following vaccines: diphtheria-tetanus-pertussis/diphtheria-tetanus-acellular pertussis (4 doses); Haemophilus influenzae type b (3 doses); poliovirus (3 doses); hepatitis B (3 doses); measles-mumps-rubella (1 dose); and overall for the basic series. Two assessment methods were used to determine the immunization status of the study children: (1) a count of all documented vaccines ("count"); and (2) only including vaccines that met minimal age and spacing intervals based on American Academy of Pediatrics and CDC recommendations ("interval assessment"). RESULTS: With the count method vaccine-specific immunization rates ranged from 88 to 95%, with overall coverage of 80% for the basic series. With the interval assessment method vaccine-specific immunization rates ranged from 74 to 92%, with overall coverage of 53% for the basic series. CONCLUSIONS: When all documented vaccines were included in the assessment, vaccine-specific immunization rates approached national goals, although overall coverage remained below 90% in this Medicaid managed care practice. The substantially lower immunization rates obtained by the interval assessment method demonstrate the importance of considering the issue of vaccine timing when interpreting immunization rates and the need for policies for revaccinating children who were immunized at less than recommended intervals. The results also have implications for provider education regarding the early administration of vaccines.

Child, Preschool↗

Lessons learned from a review of the development of selected vaccines. National Vaccine Advisory Committee.

BACKGROUND: Although the vaccine research and development network in the United States remains vibrant, its continued success requires maintaining harmonious interaction among its many components. Changing one component is likely to affect the system overall. An examination of case studies of the development of selected vaccines would allow an examination of the network as a whole. This article presents conclusions drawn from the case study review undertaken. OBJECTIVE: Successful development of vaccines is a time-intensive process requiring years of commitment from a network of scientists and a continuum of regulatory and manufacturing entities. We undertook this work to shed light on how well the vaccine development system in the United States performs. METHOD: The National Vaccine Advisory Committee examined the research and development pathways of several vaccines that reached licensure expeditiously (hepatitis B vaccine, Haemophilus influenzae type b conjugate vaccines); some that became licensed only after considerable delay (oral typhoid Ty21a vaccine, varicella vaccine); some that are at the point of imminent or recent licensure (reassortant Rhesus rotavirus vaccine, which was licensed by the Food and Drug Administration on August 30, 1998) or near submission for licensure (intranasal cold adapted influenza vaccine); and one for which clinical development is slow because of hurdles that must be overcome (respiratory syncytial virus vaccines). RESULTS: Some common themes emerged from the reviews of these vaccine "case histories": the expediting influence of a strong scientific base and rationale; the need for firm quantitation of disease burden and clear identification of target populations; the critical role played by individuals or teams who act as "champions" to overcome the inevitable obstacles; availability of relevant animal models, high-quality reagents and standardized assays to measure immune response; the absolute requirement for well designed, meticulously executed clinical trials of vaccine safety, immunogenicity, and efficacy; postlicensure measurements of the public health impact of the vaccine and a track record of the vaccine's safety and acceptance with large-scale use; and the critical need for international collaborations to evaluate vaccines against diseases of global importance that are rare in the United States (eg, typhoid fever). It was clear that the critical step-up from bench scale to pilot lots and then to large-scale production, which depends on a small group of highly trained individuals, is often a particularly vulnerable point in the development process. CONCLUSIONS: One fundamental lesson learned is that within the varied and comprehensive US vaccine development infrastructure, multiple and rather distinct paths can be followed to reach vaccine licensure. The National Vaccine Advisory Committee review process should be conducted periodically in the future to ascertain that the US vaccine development network, which has been enormously productive heretofore and has played a leadership role globally, is adapting appropriately to ensure that new, safe, and efficacious vaccines become available in a timely manner.

Drug Approval↗

A collaborative study on media for the enumeration of yeasts in foods.

A collaborative study was made to evaluate the effectivity of a general purpose medium, tryptone glucose yeast extract (TGY) agar on the detection and enumeration of yeasts from food. Nine laboratories participated in the study and compared five media (four kinds of TGY with different concentrations of glucose, one of them without tryptone, and, for comparison, dichloran rose bengal chloramphenicol (DRBC) agar). Six food samples were investigated by each laboratory and 23 additional food samples were investigated individually by different laboratories. No difference was found in the performance of media with either the samples common to all laboratories or the various samples tested in different ones. A medium consisting of tryptone, glucose and yeast extract, at any concentration of glucose tested, appeared reliable for the detection and enumeration of yeasts from foods, and its performance did not differ from that of DRBC. Omission of tryptone as recommended by ISO provided an even simpler medium of equally good performance. TGY without chloramphenicol may result in higher total counts due to the development of bacteria. DRBC incubated in light results in lower counts compared to that incubated in the dark.

Aniline Compounds↗

Prevention of bacterial endocarditis. Recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.

American Heart Association↗

Prevention of bacterial endocarditis. Recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.

Antibiotic Prophylaxis↗