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Biomedical subjects

Gregory Martin

Publications and source records attributed to Gregory Martin.

12 recordsLinked to original sources
PubMed2024

Natural variation of immune epitopes reveals intrabacterial antagonism.

Plants and animals detect biomolecules termed microbe-associated molecular patterns (MAMPs) and induce immunity. Agricultural production is severely impacted by pathogens which can be controlled by transferring immune receptors. However, most studies use a single MAMP epitope and the impact of diverse multicopy MAMPs on immune induction is unknown. Here, we characterized the epitope landscape from five proteinaceous MAMPs across 4,228 plant-associated bacterial genomes. Despite the diversity sampled, natural variation was constrained and experimentally testable. Immune perception in both Arabidopsis and tomato depended on both epitope sequence and copy number variation. For example, Elongation Factor Tu is predominantly single copy, and 92% of its epitopes are immunogenic. Conversely, 99.9% of bacterial genomes contain multiple cold shock proteins, and 46% carry a nonimmunogenic form. We uncovered a mechanism for immune evasion, intrabacterial antagonism, where a nonimmunogenic cold shock protein blocks perception of immunogenic forms encoded in the same genome. These data will lay the foundation for immune receptor deployment and engineering based on natural variation.

Epitopes↗
PubMed2024

Natural variation of immune epitopes reveals intrabacterial antagonism.

Plants and animals detect biomolecules termed Microbe-Associated Molecular Patterns (MAMPs) and induce immunity. Agricultural production is severely impacted by pathogens which can be controlled by transferring immune receptors. However, most studies use a single MAMP epitope and the impact of diverse multi-copy MAMPs on immune induction is unknown. Here we characterized the epitope landscape from five proteinaceous MAMPs across 4,228 plant-associated bacterial genomes. Despite the diversity sampled, natural variation was constrained and experimentally testable. Immune perception in both Arabidopsis and tomato depended on both epitope sequence and copy number variation. For example, Elongation Factor Tu is predominantly single copy and 92% of its epitopes are immunogenic. Conversely, 99.9% of bacterial genomes contain multiple Cold Shock Proteins and 46% carry a non-immunogenic form. We uncovered a new mechanism for immune evasion, intrabacterial antagonism, where a non-immunogenic Cold Shock Protein blocks perception of immunogenic forms encoded in the same genome. These data will lay the foundation for immune receptor deployment and engineering based on natural variation.

comparative genomics↗
PubMed2006

Long-term changes of serum chemokine levels in vaccinated military personnel.

BACKGROUND: Members of the United States Armed Forces receive a series of vaccinations during their course of service. To investigate the influence of multiple vaccinations on innate immunity, we measured concentrations of a panel of immunomodulatory and pro-inflammatory cytokines in serum samples from a group of such individuals. RESULTS: Significantly increased levels of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta and interleukin 8 (IL-8) were detected. Since these cytokines are known to have anti-human immunodeficiency virus (HIV) activity, we tested the effect of serum from these individuals on HIV-1 infectivity and susceptibility of their peripheral blood mononuclear cells (PBMCs) to HIV-1 infection in vitro. Sera from vaccinated military personnel inhibited, and their PBMCs were partially resistant to, infection by HIV-1 strains tropic to CCR5 (R5), but not to CXCR4 (X4), chemokine receptor. CONCLUSION: These findings demonstrate that increased anti-HIV chemokines can be detected in vaccine recipients up to 68 weeks following immunization.

Adult↗
PubMed2005

A 15- to 25- year follow-up study of primary Charnley low-friction arthroplasty: a single surgeon series.

Long term outcome studies are essential to determine the effectiveness and durability of a procedure. We report our 15 to 25 year clinical and radiographic follow-up with the Charnley low-friction hip arthroplasty. Four hundred and forty-seven primary Charnley hip arthroplasties were performed by a single surgeon. Ninety-eight of the 447 hips from 75 patients were available for follow up at average of 18.9 years (range 15.3 to 25.4 years). Seventy-two hips (73.5%) survived clinically. Of these 72, seventy-one stems (98.6%) and 60 sockets (83.3%) survived radiographically. Kaplan-Meier survival analysis on all 447 hips using revision as an endpoint revealed 66.2% +/- 5.7% survival at 20 years. Twenty-six hips were revised. The main reason for revision was failure of the socket. Complications included dislocation (3 of 98 hips), heterotopic ossification (7 of 98 hips), trochanteric wire breakage (6 of 98 hips), and trochanteric non-union (1 of 98 hips). Charnley low-friction hip arthroplasty is an effectiveand durable procedure. Key words: hip, arthroplasty, charnley, follow-up.

Adolescent↗
PubMed2005

Effect of labor epidural analgesia with and without fentanyl on infant breast-feeding: a prospective, randomized, double-blind study.

BACKGROUND: The influence of labor epidural fentanyl on the neonate is controversial. The purpose of this study was to determine whether epidural fentanyl has an impact on breast-feeding. METHODS: Women who previously breast-fed a child and who requested labor epidural analgesia were randomly assigned in a double-blinded manner to one of three groups: (1) no fentanyl group, (2) intermediate-dose fentanyl group (intent to administer between 1 and 150 microg epidural fentanyl), or (3) high-dose epidural fentanyl group (intent to administer > 150 microg epidural fentanyl). On postpartum day 1, the mother and a lactation consultant separately assessed whether the infant was experiencing difficulty breast-feeding, and a pediatrician assessed infant neurobehavior. All women were contacted 6 weeks postpartum to determine whether they were still breast-feeding. RESULTS: Sixty women were randomly assigned to receive no fentanyl, 59 were randomly assigned to receive an intermediate dose, and 58 were randomly assigned to receive high-dose fentanyl. On postpartum day 1, women who were randomly assigned to receive high-dose fentanyl reported difficulty breast-feeding (n = 12, 21%) more often than women who were randomly assigned to receive an intermediate fentanyl dose (n = 6, 10%), or no fentanyl (n = 6, 10%), although this did not reach statistical significance (P = 0.09). There was also no significant difference among groups in breast-feeding difficulty based on the lactation consultant's evaluation (40% difficulty in each group; P = 1.0). Neurobehavior scores were lowest in the infants of women who were randomly assigned to receive more than 150 microg fentanyl (P = 0.03). At 6 weeks postpartum, more women who were randomly assigned to high-dose epidural fentanyl were not breast-feeding (n = 10, 17%) than women who were randomly assigned to receive either an intermediate fentanyl dose (n = 3, 5%) or no fentanyl (n = 1, 2%) (P = 0.005). CONCLUSIONS: Among women who breast-fed previously, those who were randomly assigned to receive high-dose labor epidural fentanyl were more likely to have stopped breast-feeding 6 weeks postpartum than woman who were randomly assigned to receive less fentanyl or no fentanyl.

Adjuvants, Anesthesia↗
PubMed2004

Minor salivary gland biopsy in neonatal hemochromatosis.

BACKGROUND: Neonatal hemochromatosis (NH), a rare disorder seen in newborns, is defined as liver failure with extrahepatic iron deposition that spares the reticuloendothelial elements. This disorder is considered the pathologic end point of a variety of diseases that result in prenatal liver failure, and mortality without aggressive treatment is common. However, ready diagnosis remains a problem. A liver biopsy specimen showing siderosis is not specific for hemochromatosis and may be risky in patients with coagulopathy. OBJECTIVE: To describe a safe and effective method for diagnosing NH that uses lower-lip minor salivary gland biopsy and can be readily performed even in the most severe cases of coagulopathy under local anesthesia. METHODS: Eleven neonates with suspected NH were identified. After informed consent, a biopsy specimen of lower-lip tissue was taken under local anesthesia by the otolaryngology team. RESULTS: Ten of the 11 neonates had minor salivary gland tissue present (or detected) by initial frozen-section analysis. One of the 11 patients required a second biopsy owing to a lack of sufficient minor salivary gland tissue on the initial specimen, underscoring the importance of frozen-section analysis. Six of 7 neonates with NH had positive biopsy findings and the seventh had a false negative. There were 4 true negatives. Three of 7 children with NH survived, 1 requiring liver transplantation and 2 with medical treatment only. CONCLUSION: Minor salivary gland biopsy is a safe and effective way to quickly diagnose NH, a rapidly progressive, often fatal condition.

Biopsy↗
PubMed2004

ESTs, cDNA microarrays, and gene expression profiling: tools for dissecting plant physiology and development.

Gene expression profiling holds tremendous promise for dissecting the regulatory mechanisms and transcriptional networks that underlie biological processes. Here we provide details of approaches used by others and ourselves for gene expression profiling in plants with emphasis on cDNA microarrays and discussion of both experimental design and downstream analysis. We focus on methods and techniques emphasizing fabrication of cDNA microarrays, fluorescent labeling, cDNA hybridization, experimental design, and data processing. We include specific examples that demonstrate how this technology can be used to further our understanding of plant physiology and development (specifically fruit development and ripening) and for comparative genomics by comparing transcriptome activity in tomato and pepper fruit.

DNA, Complementary↗
PubMed2003

Influence of demographic and technical variables on the incidence of osteolysis in Charnley primary low-friction hip arthroplasty.

The influence of demographic and technical variables on the incidence of osteolysis in Charnley primary low-friction arthroplasty was investigated. Demographic variables included age, gender, diagnosis, and Charnley joint class. Technical variables included the design of acetabular and femoral components, subchondral plate retention versus removal, and cementing techniques. We analyzed 633 hips (in 494 patients) implanted by a single surgeon between 1970 and 1984 using Kaplan-Meier survival graphs. Radiographically determined osteolysis was defined as the end point. The incidence of osteolysis at 5 years was 2% (confidence interval [CI] +/- 0.5%); at 10 years, 8% (CI +/- 1.6%); at 15 years, 15% (CI +/- 2.2%); and at 20 years, 17% (CI +/- 3.5%). Younger patients (age < 65 years) and men were both found to have a significantly increased incidence of osteolysis (P<.05). No significant association with osteolysis was found for the other demographic and technical variables investigated. Osteolysis predates loosening and failure of hip arthroplasty. Regular assessment with the goal of earlier identification, especially in higher risk younger and male patients, is important to avoid excessive bone loss and technical difficulties in revision surgery.

Adolescent↗
PubMed2002

Deductions about the number, organization, and evolution of genes in the tomato genome based on analysis of a large expressed sequence tag collection and selective genomic sequencing.

Analysis of a collection of 120,892 single-pass ESTs, derived from 26 different tomato cDNA libraries and reduced to a set of 27,274 unique consensus sequences (unigenes), revealed that 70% of the unigenes have identifiable homologs in the Arabidopsis genome. Genes corresponding to metabolism have remained most conserved between these two genomes, whereas genes encoding transcription factors are among the fastest evolving. The majority of the 10 largest conserved multigene families share similar copy numbers in tomato and Arabidopsis, suggesting that the multiplicity of these families may have occurred before the divergence of these two species. An exception to this multigene conservation was observed for the E8-like protein family, which is associated with fruit ripening and has higher copy number in tomato than in Arabidopsis. Finally, six BAC clones from different parts of the tomato genome were isolated, genetically mapped, sequenced, and annotated. The combined analysis of the EST database and these six sequenced BACs leads to the prediction that the tomato genome encodes approximately 35,000 genes, which are sequestered largely in euchromatic regions corresponding to less than one-quarter of the total DNA in the tomato nucleus.

Arabidopsis↗
PubMed2002

Opening a bacillus anthracis-containing envelope, Capitol Hill, Washington, D.C.: the public health response.

On October 15, 2001, a U.S. Senate staff member opened an envelope containing Bacillus anthracis spores. Chemoprophylaxis was promptly initiated and nasal swabs obtained for all persons in the immediate area. An epidemiologic investigation was conducted to define exposure areas and identify persons who should receive prolonged chemoprophylaxis, based on their exposure risk. Persons immediately exposed to B. anthracis spores were interviewed; records were reviewed to identify additional persons in this area. Persons with positive nasal swabs had repeat swabs and serial serologic evaluation to measure antibodies to B. anthracis protective antigen (anti-PA). A total of 625 persons were identified as requiring prolonged chemoprophylaxis; 28 had positive nasal swabs. Repeat nasal swabs were negative at 7 days; none had developed anti-PA antibodies by 42 days after exposure. Early nasal swab testing is a useful epidemiologic tool to assess risk of exposure to aerosolized B. anthracis. Early, wide chemoprophylaxis may have averted an outbreak of anthrax in this population.

Anthrax↗