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Biomedical subjects

John J Ross

Publications and source records attributed to John J Ross.

At least 19 recordsLinked to original sources
PubMed2006

Goats, germs, and fever: Are the pyrin mutations responsible for familial Mediterranean fever protective against Brucellosis?

Mutations in the MEFV gene are highly prevalent in the Middle East and Mediterranean basin, with carrier rates of up to 1:3 in some populations. More than 50 mutations in the MEFV gene have been described. The high prevalence, multiple mutations, and geographic localization to the Middle East suggest a positive selection advantage for the abnormal gene operating in this area over the last several thousand years. To date, no satisfactory explanation of this phenomenon has been made. Rather, many harmful effects of these mutations have been described. MEFV gene mutations cause familial Mediterranean fever in homozygotes, a disease associated with recurrent febrile inflammatory episodes, and death from renal failure and amyloidosis. Heterozygotes with MEFV mutations are predisposed to premature coronary disease, and rheumatologic conditions such as Behçet's disease. MEFV mutations do not appear to protect against tuberculosis. Brucellosis is still highly endemic in the Middle East because of the traditional reliance for meat and dairy production on goats and sheep, the major vectors for this zoonosis. Brucellosis causes a prolonged febrile illness lasting for months and even years, and it may have exacted a major toll among Bronze Age peasant populations in the Middle East. The gene product for MEFV, pyrin, normally inhibits interleukin-1beta production. Mutations in MEFV result in a pro-inflammatory state, with a Th1 polarization and high levels of interferon-gamma. This may actually be protective against intracellular pathogens such as brucellosis. The possible heterozygote advantage of MEFV mutations against brucellosis may therefore be a balanced polymorphism, analogous to the protective effect against malaria that maintains high levels of sickle cell trait in sub-Saharan Africa.

Animals↗
PubMed2006

Angiogenic gene therapy as a potential therapeutic agent in chronic osteomyelitis.

Bacterial osteomyelitis is common, and outcomes are often poor. Standard therapies fail in 31% of cases, and lower extremity amputation and loss of independent functional status are common. Innovative therapies are desperately needed, particularly in diabetic patients with peripheral vascular disease at high risk for bad outcomes. Angiogenic gene therapy is a novel, logical and promising approach in these patients. Adult bone is not well vascularized. Host inflammation and bacterial toxin production result in further loss of vascularity, and produce bone necrosis. Dead bone acts as a foreign body, and is permissive for persistent infection. Poor blood supply prevents remodeling of dead bone, delivery of antibiotics, and phagocytosis of bacteria. Therefore, angiogenic gene therapy may be a useful therapeutic agent in osteomyelitis. It is reasonable to pursue studies of angiogenic agents in established animal models of chronic osteomyelitis, not only with vascular endothelial growth factor (VEGF), but also with the powerful bone angiogenic agent, placental growth factor, as well as other agents with tissue regenerative and angiogenic potential, such as sonic hedgehog, bone morphogenetic proteins, matrix metalloproteinase-9, secretoneurin, and perhaps pluripotent stem cells. If successful, animal studies could lead to pilot studies of one or more of these agents as adjunctive therapy, in addition to antibiotics, in diabetic patients with chronic osteomyelitis who have failed conventional treatment.

Animals↗
PubMed2006

Defective long-distance auxin transport regulation in the Medicago truncatula super numeric nodules mutant.

Long-distance auxin transport was examined in Medicago truncatula and in its supernodulating mutant sunn (super numeric nodules) to investigate the regulation of auxin transport during autoregulation of nodulation (AON). A method was developed to monitor the transport of auxin from the shoot to the root in whole seedlings. Subsequently, the transport was monitored after inoculation of roots with the nodulating symbiont Sinorhizobium meliloti. The sunn mutant showed an increased amount of auxin transported from the shoot to the root compared to the wild type. The auxin transport capacity of excised root segments was similar in wild type and sunn, suggesting that the difference in long-distance auxin transfer between them is due to loading in the shoot. After inoculation, wild-type seedlings showed decreased auxin loading from the shoot to the root; however, the sunn mutant failed to reduce the amount of auxin loaded. The time of reduced auxin loading correlated with the onset of AON. Quantification of endogenous auxin levels at the site of nodule initiation showed that sunn contained three times more auxin than wild type. Inoculation of sunn failed to reduce the level of auxin within 24 h, as was observed in the wild type. We propose a model for the role of auxin during AON of indeterminate legumes: 1) high levels of endogenous auxin are correlated with increased numbers of nodules, 2) inoculation of roots reduces auxin loading from the shoot to the root, and 3) subsequent reduction of auxin levels in the root inhibits further nodule initiation.

Biological Transport↗
PubMed2006

Posttraumatic stress disorder after occupational HIV exposure: two cases and a literature review.

Two healthcare workers developed disabling chronic posttraumatic stress disorder after needlestick exposures to blood from a patient infected with human immunodeficiency virus (HIV), even though both continue to test negative for HIV antibody more than 22 months after their exposures. We describe these 2 cases and review the relevant literature. Prospective studies of psychological morbidity after occupational needlestick injuries are required to determine the role of long-term psychological follow-up, counseling, and support.

Female↗
PubMed2006

Distinct roles of HF-1b/Sp4 in ventricular and neural crest cells lineages affect cardiac conduction system development.

The heterogeneous cell types of the cardiac conduction system are responsible for coordinating and maintaining rhythmic contractions of the heart. While it has been shown that the cells of the conduction system are derived from myocytes, additional cell types, including neural crest cells, may play a role in the development and maturation of these specialized cell lineages. Previous work has shown that the expression of the hf-1b gene is required for specification of the cardiac conduction system. Using Cre-Lox technology, we conditionally mutated the hf-1b gene in the ventricular and the neural crest cell lineages. Cx40 immunohistochemistry on HF-1b tissue-restricted knockouts revealed a requirement for HF-1b in the cardiomyogenic lineage. Electrophysiological studies identified a second requirement for HF-1b in the neural crest-derived cells. Absence of HF-1b in the neural crest led to atrial and atrioventricular dysfunction resulting from deficiencies in the neurotrophin receptor trkC. Therefore, in this study, we document that a single transcription factor, HF-1b, acts through two separate cell types to direct distinct functions of the cardiac conduction system.

Animals↗
PubMed2006

Seed dormancy and ABA metabolism in Arabidopsis and barley: the role of ABA 8'-hydroxylase.

We have investigated the relationship between seed dormancy and abscisic acid (ABA) metabolism in the monocot barley and the dicot Arabidopsis. Whether dormant (D) or non-dormant (ND), dry seed of Arabidopsis and embryos of dry barley grains all had similarly high levels of ABA. ABA levels decreased rapidly upon imbibition, although they fell further in ND than in D. Gene expression profiles were determined in Arabidopsis for key ABA biosynthetic [the 9-cis epoxycarotenoid dioxygenasegene family] and ABA catabolic [the ABA 8'-hydroxylase gene family (CYP707A)] genes. Of these, only the AtCYP707A2 gene was differentially expressed between D and ND seeds, being expressed to a much higher level in ND seeds. Similarly, a barley CYP707 homologue, (HvABA8'OH-1) was expressed to a much higher level in embryos from ND grains than from D grains. Consistent with this, in situ hybridization studies showed HvABA8'OH-1 mRNA expression was stronger in embryos from ND grains. Surprisingly, the signal was confined in the coleorhiza, suggesting that this tissue plays a key role in dormancy release. Constitutive expression of a CYP707A gene in transgenic Arabidopsis resulted in decreased ABA content in mature dry seeds and a much shorter after-ripening period to overcome dormancy. Conversely, mutating the CYP707A2 gene resulted in seeds that required longer after-ripening to break dormancy. Our results point to a pivotal role for the ABA 8'-hydroxylase gene in controlling dormancy and that the action of this enzyme may be confined to a particular organ as in the coleorhiza of cereals.

Abscisic Acid↗
PubMed2006

A role for ethylene in the phytochrome-mediated control of vegetative development.

Members of the phytochrome family of photoreceptors play key roles in vegetative plant development, including the regulation of stem elongation, leaf development and chlorophyll accumulation. Hormones have been implicated in the control of these processes in de-etiolating seedlings. However, the mechanisms by which the phytochromes regulate vegetative development in more mature plants are less well understood. Pea (Pisum sativum) mutant plants lacking phytochromes A and B, the two phytochromes present in this species, develop severe defects later in development, including short, thick, distorted internodes and reduced leaf expansion, chlorophyll content and CAB gene transcript level. Studies presented here indicate that many of these defects in phyA phyB mutant plants appear to be due to elevated ethylene production, and suggest that an important role of the phytochromes in pea is to restrict ethylene production to a level that does not inhibit vegetative growth. Mutant phyA phyB plants produce significantly more ethylene than WT plants, and application of an ethylene biosynthesis inhibitor rescued many aspects of the phyA phyB mutant phenotype. This deregulation of ethylene production in phy-deficient plants appears likely to be due, at least in part, to the elevated transcript levels of key ethylene-biosynthesis genes. The phytochrome A photoreceptor appears to play a prominent role in the regulation of ethylene production, as phyA, but not phyB, single-mutant plants also exhibit a phenotype consistent with elevated ethylene production. Potential interactions between ethylene and secondary plant hormones in the control of the phy-deficient mutant phenotype were explored, revealing that ethylene may inhibit stem elongation in part by reducing gibberellin levels.

Ethylenes↗
PubMed2005

Tuberculosis, bronchiectasis, and infertility: what ailed George Orwell?

In the last and most productive years of his life, George Orwell struggled with pulmonary tuberculosis, dying at the dawn of the era of chemotherapy. His case history illustrates clinical aspects of tuberculosis with contemporary relevance: the role of poverty in its spread, the limited efficacy of monotherapy, the potential toxicity of treatment, and the prominence of cachexia as a terminal symptom. Orwell's ordeals with collapse therapy may have influenced the portrayal of the tortures of Winston Smith in the novel 1984. I discuss unifying diagnoses for Orwell's respiratory problems and apparent infertility, including tuberculous epididymitis, Young syndrome, immotile cilia syndrome, and cystic fibrosis.

Antitubercular Agents↗
PubMed2005

Nodulation phenotypes of gibberellin and brassinosteroid mutants of pea.

The initiation and development of legume nodules induced by compatible Rhizobium species requires a complex signal exchange involving both plant and bacterial compounds. Phytohormones have been implicated in this process, although in many cases direct evidence is lacking. Here, we characterize the root and nodulation phenotypes of various mutant lines of pea (Pisum sativum) that display alterations in their phytohormone levels and/or perception. Mutants possessing root systems deficient in gibberellins (GAs) or brassinosteroids (BRs) exhibited a reduction in nodule organogenesis. The question of whether these reductions represent direct or indirect effects of the hormone deficiency is addressed. For example, the application of GA to the roots of a GA-deficient mutant completely restored its number of nodules to that of the wild type. Grafting studies revealed that a wild-type shoot or root also restored the nodule number of a GA-deficient mutant. These findings suggest that GAs are required for nodulation. In contrast, the shoot controlled the number of nodules that formed in graft combinations of a BR-deficient mutant and its wild type. The root levels of auxin and GA were similar among these latter graft combinations. These results suggest that BRs influence a shoot mechanism that controls nodulation and that the root levels of auxin and GA are not part of this process. Interestingly, a strong correlation between nodule and lateral root numbers was observed in all lines assessed, consistent with a possible overlap in the early developmental pathways of the two organs.

Gene Expression Regulation, Plant↗
PubMed2005

Auxin dynamics after decapitation are not correlated with the initial growth of axillary buds.

One of the first and most enduring roles identified for the plant hormone auxin is the mediation of apical dominance. Many reports have claimed that reduced stem indole-3-acetic acid (IAA) levels and/or reduced basipetal IAA transport directly or indirectly initiate bud growth in decapitated plants. We have tested whether auxin inhibits the initial stage of bud release, or subsequent stages, in garden pea (Pisum sativum) by providing a rigorous examination of the dynamics of auxin level, auxin transport, and axillary bud growth. We demonstrate that after decapitation, initial bud growth occurs prior to changes in IAA level or transport in surrounding stem tissue and is not prevented by an acropetal supply of exogenous auxin. We also show that auxin transport inhibitors cause a similar auxin depletion as decapitation, but do not stimulate bud growth within our experimental time-frame. These results indicate that decapitation may trigger initial bud growth via an auxin-independent mechanism. We propose that auxin operates after this initial stage, mediating apical dominance via autoregulation of buds that are already in transition toward sustained growth.

Flowers↗
PubMed2005

Stems of the Arabidopsis pin1-1 mutant are not deficient in free indole-3-acetic acid.

The pin1-1 mutant of Arabidopsis thaliana has been pivotal for studies on auxin transport and on the role of auxin in plant development. It was reported previously that when whole shoots were analysed, levels of the major auxin, indole-3-acetic acid (IAA) were dramatically reduced in the mutant, compared with the WT (Okada et al. 1991). The cloning of PIN1, however, provided evidence that this gene encodes a facilitator of auxin efflux, raising the question of how the pin1-1 mutation might reduce overall IAA levels as well as IAA transport. We therefore re-examined IAA levels in individual parts of pin1-1 and WT plants, focusing on inflorescence stems. Our data show that there is in fact no systemic IAA deficiency in the mutant. The previously reported difference between mutant and WT may have been due to the inclusion of reproductive structures in the WT harvest: we show here that the inflorescence itself contains high levels of IAA. We reconcile the normal IAA levels of pin1-1 inflorescence stems with their (previously-reported) reduced ability to transport IAA by presenting evidence that the auxin in mutant stems is not imported from their apical portion. Our data also indicate that levels of another auxin, indole-3-butyric acid (IBA), are very low in stems of the genotypes used in this study.

Arabidopsis↗
PubMed2005

Shakespeare's chancre: did the bard have syphilis?

Shakespeare's obsessive interest in syphilis, his clinically exact knowledge of its manifestations, the final poems of the sonnets, and contemporary gossip all suggest that he was infected with "the infinite malady." The psychological impact of venereal disease may explain the misogyny and revulsion from sex so prominent in the writings of Shakespeare's tragic period. This article examines the possibility that Shakespeare received successful treatment for syphilis and advances the following new hypothesis: Shakespeare's late-life decrease in artistic production, tremor, social withdrawal, and alopecia were due to mercury poisoning from syphilis treatment. He may also have had anasarca due to mercury-related membranous nephropathy. This medical misadventure may have prematurely ended the career of the greatest writer in the English language.

Drama↗
PubMed2005

Septic arthritis.

Septic arthritis has increased in incidence in the United States in the past two decades, and increasingly affects an older population with a greater burden of chronic illness and a higher risk for drug-resistant organisms. Successful management depends on a high diagnostic suspicion, empiric antibiotic treatment, and joint drainage. A bacteriologic diagnosis is more likely with inoculation into blood culture bottles than plating on solid media. As MRSA increases in prevalence in the community, empiric anti-biotic regimens increasingly need to be active against MRSA.

Animals↗
PubMed2005

Suppurative tenosynovitis and septic bursitis.

Suppurative tenosynovitis and septic bursitis are closed space infections of the musculoskeletal system. Appropriate antibiotics in combination with incision and drainage are generally recommended. Aggressive surgical management is particularly important in tenosynovitis to prevent tendon necrosis. Empiric antibiotic coverage should be directed toward staphylococci and streptococci. Patient characteristics and epidemiologic exposures may provide clues to unusual causative organisms that are occasionally encountered, such as Neisseria gonorrhoeae, Pasteurella multocida, atypical mycobacteria, fungi, and protothecosis.

AIDS-Related Opportunistic Infections↗
PubMed2005

Tropical and temperate pyomyositis.

Pyomyositis is a primary infection of skeletal muscle not arising from contiguous infection, presumably hematogenous in origin, and often, but not invariably, associated with abscess formation. Classically, pyomyositis is an infection of the tropics, occurring in previously active and healthy young men. Pyomyositis in temperate countries is often regarded as an infection that occurs in hosts who are immunocompromised or otherwise debilitated. However,this distinction may be somewhat artificial, as tropical pyomyositis may be partly related to underlying infection with HIV or parasites, and temperate pyomyositis has been reported in healthy and athletic persons. This article discusses the pathogenesis, clinical presentation, diagnosis, and management of pyomyositis in the tropical and temperate settings.

AIDS-Related Opportunistic Infections↗
PubMed2004

The brassinosteroid growth response in pea is not mediated by changes in gibberellin content.

The objective of this study was to increase our understanding of the relationship between brassinosteroids (BRs) and gibberellins (GAs) by examining the effects of BR deficiency on the GA biosynthesis pathway in several tissue types of pea (Pisum sativum L.). It was suggested recently that, in Arabidopsis, BRs act as positive regulators of GA 20-oxidation, a key step in GA biosynthesis [Bouquin et al. (2001) Plant Physiol 127:450-458]. However, this may not be the case in pea as GA20 levels were consistently higher in all shoot tissues of BR-deficient (lk and lkb) and BR-response (lka) mutants. The application of brassinolide (BL) to lkb plants reduced GA20 levels, and metabolism studies revealed a reduced conversion of GA19 to GA20 in epi-BL-treated lkb plants. These results indicate that BRs actually negatively regulate GA20 levels in pea. Although GA20 levels are affected by BR levels, this does not result in consistent changes in the level of the bioactive GA, GA1. Therefore, even though a clear interaction exists between endogenous BR levels and the level of GA20, this interaction may not be biologically significant. In addition to the effect of BRs on GA levels, the effect of altered GA1 levels on endogenous BR levels was examined. There was no significant difference in BR levels between the GA mutants and the wild type (wt), indicating that altered GA1 levels have no effect on BR levels in pea. It appears that the BR growth response is not mediated by changes in bioactive GA levels, thus providing further evidence that BRs are important regulators of stem elongation.

Arabidopsis↗