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Biomedical subjects

F Roberts

Publications and source records attributed to F Roberts.

At least 37 records · Page 2Linked to original sources

Localized antimicrobial peptide expression in human gingiva.

The stratified epithelia of the oral cavity are continually exposed to bacterial challenge that is initially resisted by innate epithelial factors and by the recruitment of neutrophils. Antimicrobial peptides from phagocytes and epithelia contribute to this antimicrobial barrier. Using antibodies and in situ hybridization, we explored antimicrobial peptide expression in the varied epithelia of the periodontium and in cultured gingival epithelial cells. In gingival tissue, mRNA for the beta-defensins, human beta-defensin 1 (hBD-1) and human beta-defensin 2 (hBD-2) was predominately localized in suprabasal stratified epithelium and the peptides were detected in upper epithelial layers consistent with the formation of the stratified epithelial barrier. In cultured epithelial cells, both hBD-1 and -2 peptides were detected only in differentiating, involucrin-positive epithelial cells, although hBD-2 required stimulation by proinflammatory mediators or bacterial products for expression. Beta-defensins were not detected in junctional epithelium (JE) that serves as the attachment to the tooth surface. In contrast, alpha-defensins and cathelicidin family member LL-37 were detected in polymorphonuclear neutrophils (PMNs) that migrate through the JE, a localization that persists during inflammation, when the JE and surrounding tissue are highly infiltrated with PMNs. Thus, the undifferentiated JE contains exogenously expressed alpha-defensins and LL-37, and the stratified epithelium contains endogenously expressed beta-defensins. These findings show that defensins and other antimicrobial peptides are localized in specific sites in the gingiva, are synthesized in different cell types, and are likely to serve different roles in various regions of the periodontium.

Adult↗

Counter-protective role for interleukin-5 during acute Toxoplasma gondii infection.

The role of interleukin-5 (IL-5) during Toxoplasma gondii infection was investigated by comparing disease progression in IL-5 gene deficient (IL-5-/-) mice and their wild-type (WT) counterparts on a C57BL/6 background. IL-5-/- mice infected orally with T. gondii were less susceptible to infection than WT mice as demonstrated by reduced mortality rates. Consistent with this data, orally infected IL-5-/- mice had less severe pathological changes in their small intestines than WT mice at 8 days postinfection. At this time, splenocytes and mesenteric lymph node cells derived from IL-5-/- mice produced levels of IL-12, interferon-gamma (IFN-gamma), IL-4, IL-10, and nitric oxide (measured as nitrite) similar to those derived from WT mice when stimulated with Toxoplasma lysate antigen. However, peak serum IL-12 and IFN-gamma levels (at days 6 and 8, respectively) were significantly higher in IL-5-/- mice than in WT mice. In addition, WT mice but not IL-5-/- mice had raised levels of eosinophils in their peripheral blood between days 5 and 8 following infection. Oral administration of N omega-nitro-L-arginine methyl (from day 4 postinfection) increased mortality rates in both IL-5-/- and WT mice, indicating a protective role for nitric oxide during the early stages of oral T. gondii infection. In comparison with oral infection, no difference in mortality was observed between IL-5-/- and WT mice following intraperitoneal infection with T. gondii, with all mice surviving until 35 days postinfection. Similarly, no significant differences were observed in the severity of the meningitis, perivascular cuffing, or number of microglial nodules or parasites in the brains of intraperitoneally infected mice. Together, these results demonstrate a detrimental role for IL-5 during the early stage of oral infection with T. gondii which is associated with increased small-intestine pathology, eosinophilia, and reduced plasma IL-12 and IFN-gamma levels.

Acute Disease↗

Immunological studies of chronic ocular toxoplasmosis: up-regulation of major histocompatibility complex class I and transforming growth factor beta and a protective role for interleukin-6.

A murine model was used to characterize the local immune and inflammatory response during ocular toxoplasmosis. Major histocompatibility complex (MHC) class I, normally expressed at low levels in immune-privileged sites such as the eye, was up-regulated during infection as determined by competitive reverse transcriptase (RT)-PCR and immunocytochemistry for both beta2-microglobulin and the MHC class I heavy chain. However, the eyes of chronically infected mice also had increased levels of mRNA transcripts for transforming growth factor beta, a cytokine associated with immune privilege and constitutively expressed in normal eyes. Transcripts for a number of inflammatory mediators, including interleukin-6 (IL-6), were increased during chronic infection. The role of IL-6 was further investigated by comparing disease progression and the development of the local immune response in wild-type (WT) and IL-6-deficient mice (IL-6(-/-) mice). Following infection, IL-6(-/-) mice developed more severe inflammation in the retina and vitreous humor compared with WT mice. This increased severity of disease was associated with reduced ocular IL-1alpha and increased tumor necrosis factor alpha mRNA production compared with WT mice. Moreover, the increased severity of disease in IL-6(-/-) mice correlated with increased eye parasite burden as determined by RT-PCR for the Toxoplasma gondii bradyzoite-specific LDH2 gene. These results demonstrate alterations to components of immune privilege as a result of ocular toxoplasmosis and a role for IL-6 in controlling parasite numbers and inflammation in the eye.

Animals↗

Malignant mesothelioma: a comparison of biopsy and postmortem material by light microscopy and immunohistochemistry.

AIMS: The diagnosis of malignant mesothelioma in pleural biopsies can be difficult. Survival is short and consequently many of these cases are submitted to necropsy to assist with medicolegal claims. This study compares the histological appearances and immunohistochemical profile of nine biopsy specimens with corresponding postmortem specimens. METHODS: Archival, formalin fixed, paraffin wax embedded material was obtained from nine biopsy and corresponding postmortem cases of malignant mesothelioma. The specimens were examined by light microscopy and stained with an immunohistochemical panel of 12 commercially available antibodies including CAM5.2, HBME-1, and Ber-EP4, and antibodies to thrombomodulin, calretinin, CD44H, WT-1, carcinoembryonic antigen, Leu-M1, epithelial membrane antigen and p53. RESULTS: There was greater variation in the range of histological appearances of mesotheliomas in postmortem specimens compared with biopsy specimens. There was also variability in the immunohistochemical staining pattern for certain antibodies including HBME-1, and Ber-EP4 and antibodies to calretinin, CD44H, WT-1, and p53. CONCLUSIONS: All available information should be taken into account in the histological diagnosis of malignant mesothelioma. Interpretation of the immunohistochemical profile should be regarded with some caution when only postmortem material is available. When reporting a postmortem case of suspected mesothelioma, the pathologist should seek to review all available biopsy material in conjunction with the necropsy.

Biopsy↗

Medical recommendations as joint social practice.

Treatment plans can be thought of as one of the products of a medical interaction. As such, treatment for illness has been investigated as an outcome measure and seems to reflect bias in some areas of the practice of medicine. Although the evidence for patterns of differential treatment is compelling, determining the source of treatment bias has been difficult. Based on detailed analysis of transcripts of actual interactions in general medicine and oncology clinics, we propose that treatment plans are negotiated through everyday language practices that work to maximize agreement. We demonstrate that, on the level of individual medical encounters, patient agency is both apparent and operative and that physician power does not unilaterally determine outcomes. Thus, this investigation goes beyond the abstract study of physician and patient preferences or prejudices, focusing closely on the consequences of actual talk in settings where medical recommendations are being made.

Family Practice↗

Overcoming truth telling as an obstacle to initiating safer sex: clients and health practitioners planning deception during HIV test counseling.

This article considers how deception, as a strategy for handling delicate interpersonal situations, is raised and responded to during HIV pretest counseling sessions. Two cases are presented in which clients (CLs) formulate extrarelational sexual encounters as potential obstacles to initiating safer sex practices with long-term relational partners (because reinitiating safer sex with such partners would entail admission of the extrarelational encounters). Close analysis of spoken interaction reveals that CLs display their resistance to initiating safer sex by animating, through hypothetical dialogue, their long-term partners' requests for explanation of the disruption in their usual intimate behaviors; health practitioners attempt to overcome this obstacle of "truth telling" by suggesting deception in its place. This study extends current understandings of the formulation and planning of deceptive messages in the course of actual health promotion interactions. The implications of this investigation suggest that deception may pose a viable, albeit controversial, option when promoting disease prevention behaviors, especially in delicate interpersonal interactions such as not wanting to admit an extrarelational affair.

Adolescent↗

Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies.

To identify the most accurate and useful panel to diagnose mesothelioma, we immunostained sections from 112 mesotheliomas, 18 adenocarcinomas, and 11 reactive pleural specimens with 13 antibodies. Positive results for mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were CAM5.2, 111, 18, and 11; vimentin, 30, 3, and 3; HBME-1, 75, 10, and 8; thrombomodulin, 31, 2, and 2; calretinin, 43, 6, and 11; and CD44H, 68, 10, and 4. Positive results for adenocarcinoma markers in mesotheliomas and adenocarcinomas, respectively, were carcinoembryonic antigen, 1 and 15; LeuM1, 7 and 9; and Ber-EP4, 5 and 12. All reactive pleura were negative. Positive results for markers to help distinguish mesothelioma from reactive pleura in mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were epithelial membrane antigen, 76, 17, and 6; p53, 78, 16, and 9; P-170 glycoprotein, 37, 4, and 2; and platelet-derived growth factor receptor beta, 31, 1, and 2. The differential diagnosis of mesothelioma from adenocarcinoma is based on negative markers. Individual mesothelial markers are of low sensitivity and specificity for mesothelioma. However, diagnostic accuracy is improved by the use of antibody panels. To date there are no antibodies that help distinguish mesothelioma from reactive pleura.

ATP Binding Cassette Transporter, Subfamily B↗

Intrapocket anesthesia for scaling and root planing: results of a double-blind multicenter trial using lidocaine prilocaine dental gel.

BACKGROUND: The efficacy of a novel anesthetic gel (lidocaine 25 mg/g plus prilocaine 25 mg/g in thermosetting agents) for non-invasive periodontal pocket anesthesia was evaluated. METHODS: One hundred twenty-two (122) patients in 8 centers with moderate to severe periodontitis requiring scaling and root planing (SRP) were enrolled in this multicenter, randomized, double-blind, controlled clinical trial. The active dental gel or a matching placebo gel was applied into the periodontal pocket using a blunt applicator. Following a waiting period of 30 seconds to 2 minutes, scaling and root planing were performed. If the patient had any discomfort, a second application of the gel was applied. If the patient continued to experience discomfort, conventional anesthesia was offered. After all teeth in the test quadrant had received SRP, the overall pain was assessed by the patient using a 100 mm horizontal, ungraded visual analog scale in which the left side was marked "no pain" and the right side marked "worst pain imaginable." Patients also assessed pain by using a 5-point verbal rating scale, from "no pain" to "very severe pain." RESULTS: The visual analog scale showed significant reductions in reported pain, favoring the active gel over the placebo (mean reduction, 8 mm; P <0.0005). The verbal rating scale revealed that 90% of patients treated with active gel reported no pain or mild pain compared to 64% of placebo-treated patients (P<0.001). CONCLUSIONS: Intrapocket administration of lidocaine 25 mg/g plus prilocaine 25 mg/g and thermosetting agents may be effective for pain control for scaling and root planing and may offer an alternative to infiltration anesthesia.

Administration, Topical↗

Histopathological features of ocular toxoplasmosis in the fetus and infant.

BACKGROUND: Ocular disease is a frequent manifestation of congenital Toxoplasma gondii infection. There are only limited data available in the literature concerning early stages of this disease in fetuses and infants. The purpose of our study was to characterize histopathological features in the eyes of 10 fetuses and 2 infants with congenital toxoplasmosis. METHODS: Fifteen eyes from 10 fetuses, 3 eyes from 2 premature infants, and both eyes from a 2-year-old child with congenital toxoplasmosis were examined by light microscopy. Immunohistochemical analysis to identify inflammatory cells and T gondii antigens was performed. The findings in infected eyes were compared with those of age-matched control eyes. RESULTS: Retinitis (10/18 eyes), retinal necrosis (4/18 eyes), disruption of the retinal pigment epithelium (12/18 eyes), and choroidal inflammation and congestion (15/18 eyes) were characteristic findings. Optic neuritis was present in 5 of 8 fetal eyes with associated optic nerve available for evaluation. An eye obtained from a 32-week-old fetus showed retinal rosettes at the edge of a scar. T cells predominated in retinal lesions and choroid. Parasites were identified by immunohistochemical analysis in 10 of 18 eyes. CONCLUSIONS: Ocular toxoplasmosis causes irreversible damage to the retina in utero. The fetus and infant mount inflammatory responses that may contribute to ocular damage. These findings have important implications for serological screening programs and in utero therapy.

Antigens, CD↗

Inhibition of nitric oxide production exacerbates chronic ocular toxoplasmosis.

There is considerable controversy as to the roles of parasite proliferation and the inflammatory response in destruction of the retina during Toxoplasma gondii infection. A murine model was used to investigate the role of nitric oxide in pathogenesis of chronic ocular toxoplasmosis. Increased quantities of messenger RNA (mRNA) transcripts for iNOS were detected in the eyes of chronically infected C57BL/6 mice compared with noninfected control mice. Inhibition of nitric oxide (NO) by the addition of Lomega-nitro-L-arginine methyl ester (L-NAME) to the drinking water of infected mice between weeks 4-6 of infection, exacerbated ocular inflammation. The amount of inflammation was assessed semiquantitatively in histological sections of the eye. Eyes from L-NAME treated mice showed a significant increase in inflammation of the retina (P = 0.02), choroid (P = 0.03), and vitreous (P = 0.02) compared with control mice. These results demonstrate a protective role for NO in the control of chronic, ocular toxoplasmosis.

Animals↗

Phlegmasia cerulea dolens of the upper extremity.

Phlegmasia cerulea dolens (PCD) is the term describing the painful venous congestion that results from near-total venous occlusion of a limb. It is unusual in the lower extremity but is decidedly rare in the upper extremity with only a handful of cases reported in the literature. PCD of the upper extremity usually occurs in patients with significant comorbid conditions such as severe cardiac failure or advanced malignancy. PCD of the upper extremity is associated with substantial morbidity and mortality. We present a case of upper extremity PCD in an elderly man with a complex medical history, complicated clinical course, and poor outcome that is typical for this rare disease.

Aged↗

Oesophageal rhabdomyoma.

Extracardiac rhabdomyomas are rare benign tumours showing striated muscle differentiation. Seventy percent of these lesions occur in the head and neck region. The most common sites for these lesions are the larynx, pharynx, and the floor of the mouth. There has been only one previous report of a rhabdomyoma of the oesophagus; two further cases are described.

Adult↗

HLA-class II genes modify outcome of Toxoplasma gondii infection.

Associations between Human Leukocyte Antigen (HLA) (i.e. human major histocompatibility complex [MHC]) genes and susceptibility to infections and inflammatory processes have been described, but causal relationships have not been proven. We characterized effects of HLA-DQ alleles on outcome of congenital toxoplasma infection and found that among Caucasians, the DQ3 gene frequency was significantly higher in infected infants with hydrocephalus (0.783) than infected infants without hydrocephalus (0.444) or published normal controls (0.487). We then developed a novel animal model to definitively determine the effect of these HLA DQ molecules on the severity of toxoplasmosis. Human MHC-Class II transgenes reduced parasite burden and necrosis in brains of mice infected with Toxoplasma gondii. Consistent with the observed association between DQ3 and hydrocephalus in human infants, in the murine model the DQ3(DQ8; DQB1*0302) gene protected less than DQ1 (DQ6; DQB1*0601). Our findings definitively prove a cause and effect relationship between human MHC genes and resistance to infection, provide novel means to characterise human immune responses that are protective or pathogenic in infections, and are important for vaccine development.

Animals↗

Pathogenesis of toxoplasmic retinochoroiditis.

The protozoan parasite Toxoplasma gondii is an important cause of ocular disease both in immunosuppressed and immunocompetent individuals. Non-ocular infections are not usually serious in otherwise healthy adults. In contrast, toxoplasmic retinochoroiditis is a progressive, recurring disease that can cause severe morbidity. Here, Fiona Roberts and Rima McLeod review the demography, pathology and clinical findings of this disease. They discuss mechanisms of retinal destruction and disease recurrences, and the local immunological response at this immune-privileged site.

Animals↗

Evidence for the shikimate pathway in apicomplexan parasites.

Parasites of the phylum Apicomplexa cause substantial morbidity, mortality and economic losses, and new medicines to treat them are needed urgently. The shikimate pathway is an attractive target for herbicides and antimicrobial agents because it is essential in algae, higher plants, bacteria and fungi, but absent from mammals. Here we present biochemical, genetic and chemotherapeutic evidence for the presence of enzymes of the shikimate pathway in apicomplexan parasites. In vitro growth of Toxoplasma gondii, Plasmodium falciparum (malaria) and Cryptosporidium parvum was inhibited by the herbicide glyphosate, a well-characterized inhibitor of the shikimate pathway enzyme 5-enolpyruvyl shikimate 3-phosphate synthase. This effect on T. gondii and P. falciparum was reversed by treatment with p-aminobenzoate, which suggests that the shikimate pathway supplies folate precursors for their growth. Glyphosate in combination with pyrimethamine limited T. gondii infection in mice. Four shikimate pathway enzymes were detected in extracts of T. gondii and glyphosate inhibited 5-enolpyruvyl shikimate 3-phosphate synthase activity. Genes encoding chorismate synthase, the final shikimate pathway enzyme, were cloned from T. gondii and P. falciparum. This discovery of a functional shikimate pathway in apicomplexan parasites provides several targets for the development of new antiparasite agents.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

Covered lives and seamless systems: nursing workforce development and integration in Arizona's managed-care environment.

Responding to demands that nursing leaders conduct business in creative proactive ways, the authors of this department share the work of The Robert Wood Johnson Foundation's national program, Colleagues in Caring: Regional Collaboratives for Nursing Work Force Development. The purpose of this initiative is to enhance regional and state collaborative planning and implement actions and policies to address the rapid changes occurring in the United States nursing labor market. This department, edited by Mary Fry Rapson, PhD, RN, CS, National Program Director and Rebecca B. Rice, EdD, RN, National Deputy Director, presents the ongoing work of the program, highlighting the work of the 20 individual collaboratives. Regional approaches to the expected program outcomes and specific challenges and opportunities that are unique to each region's environment are included.

Arizona↗