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Biomedical subjects

Robert W Jackson

Publications and source records attributed to Robert W Jackson.

At least 19 recordsLinked to original sources

Thioquinolobactin, a Pseudomonas siderophore with antifungal and anti-Pythium activity.

Under conditions of iron limitation Pseudomonas fluorescens ATCC 17400 produces two siderophores, pyoverdine, and a second siderophore quinolobactin, which itself results from the hydrolysis of the unstable molecule 8-hydroxy-4-methoxy-2-quinoline thiocarboxylic acid (thioquinolobactin). Pseudomonas fluorescens ATCC 17400 also displays a strong in vitro antagonism against the Oomycete Pythium, which is repressed by iron, suggesting the involvement of a siderophore(s). While a pyoverdine-negative mutant retains most of its antagonism, a thioquinolobactin-negative mutant only slowed-down Pythium growth, and a double pyoverdine-, thioquinolobactin-negative mutant, which does not produce any siderophore, totally lost its antagonism against Pythium. The siderophore thioquinolobactin could be purified and identified from spent medium and showed anti-Pythium activity, but it was quickly hydrolysed to quinolobactin, which we showed has no antimicrobial activity. Analysis of antagonism-affected transposon mutants revealed that genes involved in haem biosynthesis and sulfur assimilation are important for the production of thioquinolobactin and the expression of antagonism.

Antifungal Agents↗

Phylogenetic analysis of the pPT23A plasmid family of Pseudomonas syringae.

The pPT23A plasmid family of Pseudomonas syringae contains members that contribute to the ecological and pathogenic fitness of their P. syringae hosts. In an effort to understand the evolution of these plasmids and their hosts, we undertook a comparative analysis of the phylogeny of plasmid genes and that of conserved chromosomal genes from P. syringae. In total, comparative sequence and phylogenetic analyses were done utilizing 47 pPT23A family plasmids (PFPs) from 16 pathovars belonging to six genomospecies. Our results showed that the plasmid replication gene (repA), the only gene currently known to be distributed among all the PFPs, had a phylogeny that was distinct from that of the P. syringae hosts of these plasmids and from those of other individual genes on PFPs. The phylogenies of two housekeeping chromosomal genes, those for DNA gyrase B subunit (gyrB) and primary sigma factor (rpoD), however, were strongly associated with genomospecies of P. syringae. Based on the results from this study, we conclude that the pPT23A plasmid family represents a dynamic genome that is mobile among P. syringae pathovars.

Base Sequence↗

How cold light was introduced to arthroscopy.

In 1954, in a landmark publication, H. H. Hopkins reported that images could be transmitted through glass fibers. This stimulated many investigations and, in 1957, B. Hirschowitz at the University of Michigan, succeeded in constructing a much-needed flexible gastroscope using optic glass fibers. Coating of the fibers by glass of lower refractive index was the next major step forward. Optical fibers were thus insulated and the accuracy of the transmitted image and the light transmission capacity of the fibers were enhanced. Working with American Cystoscope Makers Inc, L. Curtiss and H. Hett were the first to use glass fibers for illumination in an endoscope, producing a flexible ureteroscope in 1960. The light transmitted by the fibers was named "cold light" because it produced little heat, but the term had been used before for other types of illumination. The first arthroscope equipped with cold light was Watanabe's arthroscope No. 22 built by Tsunekichi Fukuyo in 1967. However, Watanabe was not satisfied with the new instrument and he still preferred the conventionally illuminated No. 21 arthroscope with the offset tungsten bulb at his tip. After R. W. Jackson reintroduced the technique to North America, most American pioneers used this conventionally illuminated arthroscope as well. But the early European arthroscopists had cold light instruments made by the German manufacturers R. Wolf and K. Storz since 1969. These rod-lens cold light instruments expanded in all markets during the following decade.

Arthroscopes↗

Knee bracing for unicompartmental osteoarthritis.

Unicompartmental osteoarthritis of the knee affects millions of individuals. Most nonsurgical management of this progressive disease is primarily directed at reducing inflammation and pain with medication. Evidence supports the clinical efficacy of bracing for managing osteoarthritis of the knee. In some patients, bracing significantly reduces pain, increases function, and reduces excessive loading to the damaged compartment. A variety of health and functional status instruments, as well as radiologic techniques and biomechanical investigations, has been used to evaluate the unloading capabilities of these braces. Although changes in angulation are relatively minimal, the braces have been shown to load share and thus reduce the stresses in the degenerated medial compartment of the knee.

Braces↗

Exposure to host resistance mechanisms drives evolution of bacterial virulence in plants.

Bacterial pathogenicity to plants and animals has evolved through an arms race of attack and defense. Key players are bacterial effector proteins, which are delivered through the type III secretion system and suppress basal defenses . In plants, varietal resistance to disease is based on recognition of effectors by the products of resistance (R) genes . When recognized, the effector or in this scenario, avirulence (Avr) protein triggers the hypersensitive resistance reaction (HR), which generates antimicrobial conditions . Unfortunately, such gene-for-gene-based resistance commonly fails because of the emergence of virulent strains of the pathogen that no longer trigger the HR . We have followed the emergence of a new virulent pathotype of the halo-blight pathogen Pseudomonas syringae pv. phaseolicola within leaves of a resistant variety of bean. Exposure to the HR led to the selection of strains lacking the avirulence (effector) gene avrPphB (or hopAR1), which triggers defense in varieties with the matching R3 resistance gene. Loss of avrPphB was through deletion of a 106 kb genomic island (PPHGI-1) that shares features with integrative and conjugative elements (ICElands) and also pathogenicity islands (PAIs) in diverse bacteria . We provide a molecular explanation of how exposure to resistance mechanisms in plants drives the evolution of new virulent forms of pathogens.

Bacterial Proteins↗

Changes in race-specific virulence in Pseudomonas syringae pv. phaseolicola are associated with a chimeric transposable element and rare deletion events in a plasmid-borne pathogenicity island.

Virulence for bean and soybean is determined by effector genes in a plasmid-borne pathogenicity island (PAI) in race 7 strain 1449B of Pseudomonas syringae pv. phaseolicola. One of the effector genes, avrPphF, confers either pathogenicity, virulence, or avirulence depending on the plant host and is absent from races 2, 3, 4, 6, and 8 of this pathogen. Analysis of cosmid clones and comparison of DNA sequences showed that the absence of avrPphF from strain 1448A is due to deletion of a continuous 9.5-kb fragment. The remainder of the PAI is well conserved in strains 1448A and 1449B. The left junction of the deleted region consists of a chimeric transposable element generated from the fusion of homologs of IS1492 from Pseudomonas putida and IS1090 from Ralstonia eutropha. The borders of the deletion were conserved in 66 P. syringae pv. phaseolicola strains isolated in different countries and representing the five races lacking avrPphF. However, six strains isolated in Spain had a 10.5-kb deletion that extended 1 kb further from the right junction. The perfect conservation of the 28-nucleotide right repeat of the IS1090 homolog in the two deletion types and in the other 47 insertions of the IS1090 homolog in the 1448A genome strongly suggests that the avrPphF deletions were mediated by the activity of the chimeric mobile element. Our data strongly support a clonal origin for the races of P. syringae pv. phaseolicola lacking avrPphF.

Amino Acid Sequence↗

Whole-genome sequence analysis of Pseudomonas syringae pv. phaseolicola 1448A reveals divergence among pathovars in genes involved in virulence and transposition.

Pseudomonas syringae pv. phaseolicola, a gram-negative bacterial plant pathogen, is the causal agent of halo blight of bean. In this study, we report on the genome sequence of P. syringae pv. phaseolicola isolate 1448A, which encodes 5,353 open reading frames (ORFs) on one circular chromosome (5,928,787 bp) and two plasmids (131,950 bp and 51,711 bp). Comparative analyses with a phylogenetically divergent pathovar, P. syringae pv. tomato DC3000, revealed a strong degree of conservation at the gene and genome levels. In total, 4,133 ORFs were identified as putative orthologs in these two pathovars using a reciprocal best-hit method, with 3,941 ORFs present in conserved, syntenic blocks. Although these two pathovars are highly similar at the physiological level, they have distinct host ranges; 1448A causes disease in beans, and DC3000 is pathogenic on tomato and Arabidopsis. Examination of the complement of ORFs encoding virulence, fitness, and survival factors revealed a substantial, but not complete, overlap between these two pathovars. Another distinguishing feature between the two pathovars is their distinctive sets of transposable elements. With access to a fifth complete pseudomonad genome sequence, we were able to identify 3,567 ORFs that likely comprise the core Pseudomonas genome and 365 ORFs that are P. syringae specific.

Bacterial Proteins↗

Genetic characterization of Pseudomonas fluorescens SBW25 rsp gene expression in the phytosphere and in vitro.

The plant-colonizing Pseudomonas fluorescens strain SBW25 harbors a gene cluster (rsp) whose products show similarity to type III protein secretion systems found in plant and animal pathogens. Here we report a detailed analysis of the expression and regulation of the P. fluorescens rsp pathway, both in the phytosphere and in vitro. A combination of chromosomally integrated transcriptional reporter fusions, overexpressed regulatory genes, and specific mutants reveal that promoters controlling expression of rsp are actively transcribed in the plant rhizosphere but not (with the exception of the rspC promoter) in the phyllosphere. In synthetic medium, regulatory (rspL and rspR) and structural (rspU, plus the putative effector ropE) genes are poorly expressed; the rspC promoter is subject to an additional level of regulatory control. Ectopic expression of regulatory genes in wild-type and mutant backgrounds showed that RspR controls transcription of the alternate sigma factor, rspL, and that RspL controls expression of gene clusters encoding structural genes. Mutation of rspV did not affect RspR-mediated expression of rspU. A search for additional regulators revealed two candidates--one with a role in the conversion of alanine to pyruvate--suggesting that expression of rsp is partly dependent upon the metabolic status of the cell. Mutations in rsp regulators resulted in a significant reduction in competitive colonization of the root tips of sugar beet seedlings but also caused a marked increase in the lag phase of laboratory-grown cultures, indicating that rsp regulatory genes play a more significant general role in the function of P. fluorescens SBW25 than previously appreciated.

Arabidopsis↗

Sutureless avascular meniscal repair with a photoactive naphthalimide compound: a preliminary animal study.

PURPOSE: The purpose of this study was to evaluate the ability of 2 new photoactive naphthalimide compounds to repair a lesion in the avascular zone of the meniscus. TYPE OF STUDY: In vivo animal study. METHODS: Ten Barbados sheep were used as the animal model. Under anesthesia, the left knee joint was opened and 2 identical lesions were produced in the avascular zone of the medial meniscus. The posterior horn lesion was left alone and used as the control and the lesion in the anterior horn was repaired using the photoactive laser technique. The photoactive laser technique involved placing small amounts of a naphthalimide compound into the lesion and then irradiating the site with a laser (457 nm and 1.8 W/cm2) for 6 minutes. Two different versions of the naphthalimide compound were produced and divided between the 10 animals. The joint was then flushed with normal saline and closed in layers with resorbable sutures. Four animals were euthanized at the end of 1 month and 6 animals were euthanized at the end of 3 months. After death, the medial meniscus was exposed, dissected free, and then placed in 10% buffered formalin for histologic preparation and staining. RESULTS: At 1 month, the control lesions grossly showed no repair and the photochemically repaired lesions appeared to be bonded. The photochemically repaired lesions showed some bridging by an eosinophilic amorphous-appearing substance. The previous cleft within the fibrocartilaginous structure had disappeared, and early formation of connective tissue fibers was identified. However, some reduction in cellularity was seen in these tissue sections. At 3 months, again the control lesions did not show any repair response, while the photochemically repaired lesions showed results similar to the animals at 1 month, but with a less consistent pattern of tissue bonding and remodeling. The reduced tissue cellularity was still noted. There was no discernible difference between the naphthalimide compounds. CONCLUSIONS: These preliminary results demonstrate the potential usefulness of this photochemical bonding for the treatment of avascular meniscal lesions. Additional research will be necessary to fully understand the mechanism of this repair and optimize its use before any human trials. CLINICAL RELEVANCE: This is a preliminary animal study investigating the short-term in vivo effects of a novel photochemical compound for the repair of meniscal lesions. This repair may someday be valuable in the repair of avascular meniscal lesions.

1-Naphthylamine↗

Eugen Bircher (1882-1956) the first knee surgeon to use diagnostic arthroscopy.

Eugen Bircher was a strong advocate of diagnostic arthroscopy as shown in several papers on the topic of internal derangements of the knee published between 1921 and 1926. During that time, he performed about 60 endoscopic procedures, which usually preceded a meniscectomy. We believe that this was the first time arthroscopy was used in a large scale for clinical purposes. Bircher was the head surgeon of the busy provincial Aarau General Hospital, a right-wing politician, and a highly ranked army officer. His interest in knee surgery was supported by his friend Fritz Steinmann, who was the "man of the pin" and an early promoter of skeletal traction for fracture treatment. Bircher believed in the early surgical treatment of meniscal lesions and, later, in the reconstruction of cruciate ligament lesions. He used the Jacobaeus thoracolaparoscope for arthroscopy, but it had poor endoscopic qualities. The electric lamp at the tip of the optical device was not mechanically protected and was therefore endangered by every manipulation within the joint space. Also, the 90 degrees optical system delivered a dark image. By the late 1920s, Bircher had developed the technique of double-contrast arthrography, and he gave up endoscopy by 1930. In 1935, he left surgery and took a military command in the Swiss army; later he was a representative of the Farmers Party in the National Parliament until his death.

Arthrography↗

The results of arthroscopic lavage and debridement of osteoarthritic knees based on the severity of degeneration: a 4- to 6-year symptomatic follow-up.

PURPOSE: A clinically and arthroscopically oriented staging system based on the severity of the degenerative process has been used in the assessment of the results of arthroscopic lavage and debridement of osteoarthritic (OA) knees. TYPE OF STUDY: Retrospective case series. METHODS: For eighteen months, commencing January 1995, every case of previously untreated OA referred for definitive treatment was clinically classified into 1 of 4 stages of increasing degeneration. Excluded were patients who were treated nonoperatively, by replacement arthroplasty or marrow stimulation techniques. A group of 121 cases treated by arthroscopic lavage and debridement were available for review with a 4 to 6 year follow-up. RESULTS: Arthroscopic lavage and debridement carried out in the earlier stages of the degenerative process resulted in significant relief of symptoms for reasonably long periods of time. The more advanced stages of degeneration commonly experienced some temporary relief from arthroscopic lavage and debridement, but the amount of improvement was unpredictable. CONCLUSIONS: The surgeon's armamentarium for the treatment of degenerative arthritis unresponsive to conservative treatment methods should involve minimal interventional arthroscopy at an earlier, rather than a later stage in the disease process. It is recommended that the arthroscopist be conservative in the surgical debridement, removing only the fibrillated and scaling fragments of articular cartilage.

Adult↗

A tyrosine hydroxylase microsatellite and hemodynamic response to stress in a multi-ethnic sample of youth.

OBJECTIVE: Behavioral stress is believed to have an impact on cardiovascular health. As the rate-limiting enzyme in the pathway for catecholamine synthesis, tyrosine hydroxylase is a candidate gene for variability in cardiovascular function. The aim of this study was to determine whether a relationship exists between a tyrosine hydroxylase microsatellite and resting hemodynamic function, and/or hemodynamic responsivity to laboratory stress. DESIGN: Subjects underwent 2 laboratory stressors: a video game challenge and a social competence interview. SETTING: The stressors were administered in a laboratory setting. PARTICIPANTS: Subjects were 292 10- to 20-year-old normotensive African-American and European-American twin pairs. MAIN OUTCOME MEASURES: Blood pressure (BP) and heart rate (HR) were measured at rest and in response to the stressors. RESULTS: Chi-square analyses using re-sampling to account for the twin design indicated that allele and genotype frequencies were significantly different between European Americans and African Americans (P < or = .0001). Analyses of variance indicated that the 184 and 199 bp alleles were associated with an attenuation of the hemodynamic response to stress with increasing age (P < or = .003, P < or = .002, respectively), while the 188 bp allele was associated with a higher resting systolic blood pressure (SBP) (P < or = .02), and greater hemodynamic response to stress with increasing BMI (P < or = .02). CONCLUSIONS: This study showed that in a multi-ethnic sample of normotensive adolescents, specific alleles of this tyrosine hydroxylase microsatellite were associated with protective or deleterious cardiovascular effects with subjects at rest and responding to stress.

Adolescent↗

The effect of elective cesarean delivery and intrapartum infection on fetal lymphocyte activation and susceptibility to HIV infection.

OBJECTIVE: Mother-to-child transmission of the human immunodeficiency virus may be reduced with elective cesarean delivery before labor. Because immune activation enhances the human immunodeficiency virus infection, we hypothesized that fetal lymphocytes that are obtained at elective cesarean delivery may be less activated, therefore less susceptible to human immunodeficiency virus infection than cells that are obtained after normal spontaneous vaginal delivery at term. A second hypothesis was that intrapartum infection correlates with increased lymphocyte activation and susceptibility to human immunodeficiency virus infection. STUDY DESIGN: Samples were obtained after normal spontaneous vaginal delivery (n = 13), elective cesarean delivery (n = 12), chorioamnionitis (n = 5), and preterm labor (n = 6). Activation markers were measured by flow cytometry, and cord blood mononuclear cells were infected with the human immunodeficiency virus. RESULTS: Cell activation was comparable within the normal spontaneous vaginal delivery and elective cesarean delivery groups; there was no difference in susceptibility to in vitro human immunodeficiency virus infection. Intrapartum infection (chorioamnionitis, preterm labor) was associated with increased cell activation. Chorioamnionitis/preterm labor also tended to increase cord blood mononuclear cell susceptibility to human immunodeficiency virus infection. CONCLUSION: Labor did not activate fetal lymphocytes or alter susceptibility to human immunodeficiency virus infection compared with elective cesarean delivery. Intrapartum infection was associated with cell activation, and there was a trend toward increased susceptibility to human immunodeficiency virus infection. These data suggest that fetal lymphocyte activation correlates with susceptibility to human immunodeficiency virus infection and may account for the increased mother-to-child transmission of the human immunodeficiency virus that has been seen in association with chorioamnionitis and preterm labor.

Cesarean Section↗