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Robert G Feldman

Publications and source records attributed to Robert G Feldman.

8 recordsLinked to original sources
PubMed2005

Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor.

Intrauterine infection has been frequently linked with preterm labor before 30 wk of human pregnancy. Many different species of organisms have been detected, leading to the suggestion that infection-induced preterm labor is a generic inflammatory response to organisms rather than a specific response to a limited number of pathogens. The detection of organisms by microbiological culture is a laborious and unreliable process, so the aim of this study was to harness modern molecular techniques to detect organisms in tissues from human pregnancy. A DNA probe specific for conserved regions of bacterial 16S ribosomal RNA sequence was designed and labeled with fluorescein for fluorescence in situ hybridization. Organisms were detected in the great majority (>80%) of fetal membranes after prolonged premature rupture of the fetal membranes and after preterm labor, which was consistent with previous data. Organisms were also detected in fetal membranes after preterm delivery without labor and in term deliveries (with or without labour). Inflammatory cells were found frequently in the amnion or chorion of preterm fetal membranes but not in term tissues. Our primary finding is that fluorescence in situ hybridization is an appropriate method to detect organisms in human fetal membranes. In addition, our data show that bacteria may be present in fetal membranes without necessarily causing an inflammatory response, so the mere presence of bacteria may not be sufficient to cause preterm labor.

Antigens, CD↗
PubMed2005

Efficacy of a physical therapy program in patients with Parkinson's disease: a randomized controlled trial.

OBJECTIVE: To investigate the effects of a physical therapy (PT) program in groups of people with Parkinson's disease (PD). DESIGN: Randomized controlled trial with a crossover design. SETTING: Two outpatient rehabilitation clinics in Boston and Amsterdam, respectively. PARTICIPANTS: Sixty-eight subjects diagnosed with typical, idiopathic PD, Hoehn and Yahr stage II or III, and stable medication use. INTERVENTION: Group A received PT and medication therapy (MT) for the first 6 weeks, followed by MT only for the second 6 weeks. Group B received only MT for the first 6 weeks and PT and MT for the second 6 weeks. MAIN OUTCOME MEASURES: The Sickness Impact Profile (SIP-68), the mobility portion of the SIP-68, the Unified Parkinson's Disease Rating Scale (UPDRS), and comfortable walking speed (CWS) at baseline, 6-week, 12-week, and 3-month follow-up. RESULTS: At 6 weeks, differences between groups were significant for the SIP mobility ( P =.015; effect size [ES]=.55), for CWS ( P =.012; ES=.49), for the activities of daily living (ADL) section of the UPDRS ( P =.014; ES=.45), and for the total UPDRS ( P =.007; ES=.56). The total SIP and the mentation and motor sections of the UPDRS did not differ significantly between groups. Significant differences were found at 3 months compared with baseline for CWS, the UPDRS ADL, and total scores. CONCLUSIONS: People with PD derive benefits in the short term from PT group treatment, in addition to their MT, for quality of life related to mobility, CWS, and ADLs; long-term benefits were found in CWS, UPDRS ADL, and total scores but varied between groups.

Activities of Daily Living↗
PubMed2005

Vaccination against group B streptococcus.

Streptococcus agalactiae (Group B streptococcus) is an important cause of disease in infants, pregnant women, the elderly and in immunosuppressed adults. An effective vaccine is likely to prevent the majority of infant disease (both early and late onset), as well as Group B streptococcus-related stillbirths and prematurity, to avoid the current real and theoretical limitations of intrapartum antibiotic prophylaxis, and to be cost effective. The optimal time to administer such a vaccine would be in the third trimester of pregnancy. The main limitations on the production of a Group B streptococcus vaccine are not technical or scientific, but regulatory and legal. A number of candidates including capsular conjugate vaccines using traditional carrier proteins such as tetanus toxoid and mutant diphtheria toxin CRM197, as well as Group B streptococcus-specific proteins such as C5a peptidase, protein vaccines using one or more Group B streptococcus surface proteins and mucosal vaccines, have the potential to be successful vaccines. The capsular conjugate vaccines using tetanus and CRM197 carrier proteins are the most advanced candidates, having already completed Phase II human studies including use in the target population of pregnant women (tetanus toxoid conjugate), however, no definitive protein conjugates have yet been trialed. However, unless the regulatory environment is changed specifically to allow the development of a Group B streptococcus vaccine, it is unlikely that one will ever reach the market.

Humans↗
PubMed2003

Novel protein vaccine candidates against Group B streptococcal infection identified using alkaline phosphatase fusions.

Using an alkaline phosphatase-based genetic screening method, we identified a number of proteins that are potentially located on the outer surface of Group B streptococcus (Streptococcus agalactiae). In an enzyme-linked immunosorbent assay, antisera raised against two of the proteins, the streptococcal yutD homologue and a subunit of an ABC transporter, recognised clinically important serotypes of Group B streptococcus. In a neonatal rat model, purified IgG from the sera conferred significant levels of protection against a lethal challenge infection. The proteins identified show potential as protein subunit candidates for vaccines against Group B streptococcal disease in neonates.

Alkaline Phosphatase↗
PubMed2002

PARK3 influences age at onset in Parkinson disease: a genome scan in the GenePD study.

Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P=.02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD.

Adult↗
PubMed2002

Identification of major outer surface proteins of Streptococcus agalactiae.

To identify the major outer surface proteins of Streptococcus agalactiae (group B streptococcus), a proteomic analysis was undertaken. An extract of the outer surface proteins was separated by two-dimensional electrophoresis. The visualized spots were identified through a combination of peptide sequencing and reverse genetic methodologies. Of the 30 major spots identified as S. agalactiae specific, 27 have been identified. Six of these proteins, previously unidentified in S. agalactiae, were sequenced and cloned. These were ornithine carbamoyltransferase, phosphoglycerate kinase, nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase, purine nucleoside phosphorylase, enolase, and glucose-6-phosphate isomerase. Using a gram-positive expression system, we have overexpressed two of these proteins in an in vitro system. These recombinant, purified proteins were used to raise antisera. The identification of these proteins as residing on the outer surface was confirmed by the ability of the antisera to react against whole, live bacteria. Further, in a neonatal-animal model system, we demonstrate that some of these sera are protective against lethal doses of bacteria. These studies demonstrate the successful application of proteomics as a technique for identifying vaccine candidates.

Amino Acid Sequence↗
PubMed2002

Characterization of Salmonella enterica derivatives harboring defined aroC and Salmonella pathogenicity island 2 type III secretion system (ssaV) mutations by immunization of healthy volunteers.

The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica serovar Typhi (Ty2 Delta aroC Delta ssaV, designated ZH9) and S. enterica serovar Typhimurium (TML Delta aroC Delta ssaV, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 10(7), 10(8), or 10(9) CFU. ZH9 was well tolerated, not detected in blood, nor persistently excreted in stool. Six of nine volunteers elicited anti-serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting cell (ASC) responses, with three of three vaccinees receiving 10(8) and two of three receiving 10(9) CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 10(8) and 10(9) CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 10(9) CFU of WT05 mounted detectable serovar Typhimurium LPS-specific ASC responses and serum antibody responses were variable. These data indicate that mutations in type III secretion systems may provide a route to the development of live vaccines in humans and highlight significant differences in the potential use of serovars Typhimurium and Typhi.

Bacterial Proteins↗