Endogenous Presentation of CD8+ T Cell Epitopes from Epstein-Barr Virus–encoded Nuclear Antigen 1

Epstein-Barr virus (EBV)-encoded nuclear antigen (EBNA)1 is thought to escape cytotoxic T lymphocyte (CTL) recognition through either self-inhibition of synthesis or by blockade of proteasomal degradation by the glycine-alanine repeat (GAr) domain. Here we show that EBNA1 has a remarkably varied cell type-dependent stability. However, these different degradation rates do not correspond to the level of major histocompatibility complex class I-restricted presentation of EBNA1 epitopes. In spite of the highly stable expression of EBNA1 in B cells, CTL epitopes derived from this protein are efficiently processed and presented to CD8(+) T cells. Furthermore, we show that EBV-infected B cells can readily activate EBNA1-specific memory T cell responses from healthy virus carriers. Functional assays revealed that processing of these EBNA1 epitopes is proteasome and transporter associated with antigen processing dependent. We also show that the endogenous presentation of these epitopes is dependent on the newly synthesized protein rather than the long-lived stable EBNA1. Based on these observations, we propose that defective ribosomal products, not the full-length antigen, are the primary source of endogenously processed CD8(+) T cell epitopes front EBNA1.

Case report: unusual presentation of Fasciolopsis buski in a Viet Namese child

A Viet Namese child presented with a history of abdominal pain. Shortly afterwards, he vomited eight live trematode flukes that were collected and morphologically identified as Fasciolopsis buski. The identification was confirmed by DNA analysis. Adult worms of F buski from humans are very rarely seen except at autopsy, and this is the first such report from Viet Nam. (C) 2003 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Clinical presentation of metabolic alkalosis in an adult patient with cystic fibrosis

In subtropical and tropical climates, dehydration is common in cystic fibrosis patients with respiratory exacerbations. This may lead to a clinical presentation of metabolic alkalosis with associated hyponatraemia and hypochloraemia. An adult cystic fibrosis patient who presented with a severe respiratory exacerbation accompanied by metabolic alkalosis is presented and the effects of volume correction are reported.

The role of CD4(+) and CD8(+) T cells on antibody production by murine Peyer's patch cells following mucosal presentation of Actinomyces viscosus

The aim of this study was to determine the role of CD4 and CD8 cells on specific antibody production by murine Peyer's patch (PP) cells after oral immunization with Actinomyces viscosus in mice. Female DBA/2 mice were orally immunized with three low doses of heat-killed A. viscosus. Sham-immunized mice served as a control group. Mice were depleted of CD4 or CD8 cells by intraperitoneal injection of anti-CD4 or anti-CD8 antibodies daily for 3 days before oral immunization. One week after the last oral immunization, PPs were removed and cell suspensions were cultured with A. viscosus. Specific antibody production in the culture supernatants was assessed by enzyme-linked immunosorbent assay. The results showed that oral immunization with A. viscosus induced a predominant specific immunoglobulin A (IgA) response by PP cells and, to a lesser extent, IgM antibodies. Depletion of CD4 but not CD8 cells suppressed the production of specific antibodies. These results suggest that oral immunization with low doses of A. viscosus may induce the production of specific antibodies by murine PP cells in a CD4-cell-dependent fashion.

Impaired Antigen Presentation and Effectiveness of Combined Active/Passive Immunotherapy for Epithelial Tumors

Background: Although immunization with tumor antigens can eliminate many transplantable tumors in animal models, immune effector mechanisms associated with successful immunotherapy of epithelial cancers remain undefined. Methods: Skin from transgenic mice expressing the cervical cancer-associated tumor antigen human papillornavirus type 16 (HPV16) E6 or E7 proteins from a keratin 14 promoter was grafted onto syngeneic, non-transgenic mice. Skin graft rejection was measured after active immunization with HPV16 E7 and adoptive transfer of antigen-specific T cells. Cytokine secretion of lymphocytes from mice receiving skin grafts and immunotherapy was detected by enzyme-linked immunosorbent assay, and HPV16 E7-specific memory CD8(+) T cells were detected by flow cytometry and ELISPOT. Results: Skin grafts containing HPV16 E6- or E7-expressing keratinocytes were not rejected spontaneously or following immunization with E7 protein and adjuvant. Adoptive transfer of E7-specific T-cell receptor transgenic CD8(+) T cells combined with immunization resulted in induction of antigen-specific interferon gamma-secreting CD8(+) T cells and rejection of HPV16 E7-expressing grafts. Specific memory CD8(+) T cells were generated by immunotherapy. However, a further HPV16 E7 graft was rejected from animals with memory T cells only after a second E7 immunization. Conclusions: Antigen-specific CD8(+) T cells can destroy epithelium expressing HPV16 E7 tumor antigen, but presentation of E7 antigen from skin is insufficient to reactivate memory CD8(+) T cells induced by immunotherapy. Thus, effective cancer immunotherapy in humans may need to invoke sufficient effector as well as memory T cells.

The natural jurisprudence of Jean Barbeyrac: translation as an art of political adjustment

The article makes the case for redescribing Jean Barbeyrac [1674-1744], the great French translator and influential glossator of seventeenth-century Latin natural-law texts, as something quite other than a neutral mediator of Samuel Pufendorf. To consider the specific religious and political charge of his strategies as translator is to recognize the independence of Barbeyrac's Huguenot stance on natura; jurisprudence. This stance is provoked by the profound challenge that Pufendorf's radical post-Wespthalian secularizing of civil authority posed for a Huguenot: how to grant that the state had legitimate authority to regulate all external conduct, but at the same time preserve an inviolable moral space for the exercise of individual conscience. The argument--pointing to Barbeyrac's construction of a 'Lockeanized' Pufendorf--rests both on his famous presentation of Leibniz's critique of Pufendorf's De officio hominis et civis and on more neglected elements of Barbeyrac's corpus.

Spreading and synchronization of intrinsic signals in visual cortex of macaque monkey evoked by a localized visual stimulus

Spatio-temporal maps of the occipital cortex of macaque monkeys were analyzed using optical imaging of intrinsic signals. The images obtained during localized visual stimulation (IS) were compared with the images obtained on presentation of a blank screen (IB). We first investigated spontaneous variations of the intrinsic signals by analyzing the 100 IBs for each of the three cortical areas. Slow periodical activation was observed in alternation over the cortical areas. Cross-correlation analysis indicated that synchronization of spontaneous activation only took place within each cortical area, but not between them. When a small, drifting grating (2degreesX2degrees) was presented on the fovea. a dark spot appeared in the optical image at the cortical representation of this retinal location. It spread bilaterally along the border between V1 and V2, continuing as a number of parallel dark bands covering a large area of the lateral surface of V1. Cross-correlation analysis showed that during visual stimulation the intrinsic signals over all of the three cortical areas were synchronized, with in-phase activation of V1 and V2 and anti-phase activation of V4 and V1/V2. The significance of these extensive synergistic and antagonistic interactions between different cortical areas is discussed. (C) 2003 Elsevier B.V. All rights reserved.

Tissue Doppler imaging for evaluation of myocardial function in patients with diabetes mellitus

Purpose of review Heart failure and diabetes mellitus are frequently associated, and diabetes appears to potentiate the clinical presentation of heart failure related to other causes. The purpose of this review is to examine recent advances in the application of tissue Doppler imaging for the assessment of diabetic heart disease. Recent findings Recent studies have documented that both myocardial systolic and diastolic abnormalities can be identified in apparently healthy patients with diabetes and no overt cardiac dysfunction. Interestingly, these are disturbances of longitudinal function, with compensatory increases of radial function-suggesting primary involvement of the subendocardium, which is a hallmark of myocardial ischemia. Despite this, there is limited evidence that diabetic microangiopathy is responsible-with reduced myocardial blood volume rather than reduced resting flow, and at least some evidence suggesting a normal increment of tissue velocity with stress. Finally, a few correlative studies have shown association of diabetic myocardial disease with poor glycemic control, while angiotensin converting enzyme inhibition may be protective. Summary Tissue Doppler imaging (and the related technique of strain rate imaging) appears to be extremely effective for the identification of subclinical LV dysfunction in diabetic patients It is hoped that the recognition of this condition will prompt specific therapy to prevent the development of overt LV dysfunction.

Play it again: did this melody occur more frequently or was it heard more recently? The role of stimulus familiarity in episodic recognition of music

Episodic recognition of novel and familiar melodies was examined by asking participants to make judgments about the recency and frequency of presentation of melodies over the course of two days of testing. For novel melodies, recency judgments were poor and participants often confused the number of presentations of a melody with its day of presentation; melodies heard frequently were judged as have been heard more recently than they actually were. For familiar melodies, recency judgments were much more accurate and the number of presentations of a melody helped rather than hindered performance. Frequency judgments were generally more accurate than recency judgments and did not demonstrate the same interaction with musical familiarity. Overall, these findings suggest that (1) episodic recognition of novel melodies is based more on a generalized feeling of familiarity than on a specific episodic memory, (2) frequency information contributes more strongly to this generalized memory than recency information, and (3) the formation of an episodic memory for a melody depends either on the overall familiarity of the stimulus or the availability of a verbal label. (C) 2004 Elsevier B.V. All rights reserved.

Prevalence of whole-body skin self-examination in a population at high risk for skin cancer (Australia)

Objective: Whole-body skin self-examination (SSE) with presentation of suspicious lesions to a physician may improve early detection of melanoma. The aim of this study was to establish the prevalence and determinants of SSE in a high-risk population in preparation for a community-based randomised controlled trial of screening for melanoma. Methods: A telephone survey reached 3110 residents older than 30 years (overall response rate of 66.9%) randomly selected from 18 regional communities in Queensland, Australia. Results: Overall, 804 (25.9%) participants reported whole-body SSE within the past 12 months and 1055 (33.9%) within the past three years. Whole-body SSE was associated in multivariate logistic regression analysis with younger age (< 50 years); higher education; having received either a whole-body skin examination, recommendation or instruction on SSE by a primary care physician; giving skin checks a high priority; concern about skin cancer and a personal history of skin cancer. Conclusion: Overall, the prevalence of SSE in the present study is among the highest yet observed in Australia, with about one-third of the adult population reporting whole-body SSE in the past three years. People over 50 years, who are at relatively higher risk for skin cancer, currently perform SSE less frequently than younger people.

Lymphoproliferative disease of the ocular adnexa: A clinical and pathologic study with statistical analysis of 69 patients

Purpose: To evaluate the clinical features, treatment, and outcomes of a cohort of patients with ocular adnexal lymphoproliferative disease classified according to the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms and to perform a robust statistical analysis of these data. Methods: Sixty-nine cases of ocular adnexal lymphoproliferative disease, seen in a tertiary referral center from 1992 to 2003, were included in the study. Lesions were classified by using the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms classification. Outcome variables included disease-specific Survival, relapse-free survival, local control, and distant control. Results: Stage IV disease at presentation, aggressive lymphoma histology, the presence of prior or concurrent systemic lymphoma at presentation, and bilateral adnexal disease were significant predictors for reduced disease-specific survival, local control, and distant control. Multivariate analysis found that aggressive histology and bilateral adnexal disease had significantly reduced disease-specific Survival. Conclusions: The typical presentation of adnexal lymphoproliferative disease is with a painless mass, swelling, or proptosis; however, pain and inflammation occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor histology, primary or secondary status, and whether the process was unilateral or bilateral were significant variables for disease outcome. In this study, distant spread of lymphoma was lower in patients who received greater than 20 Gy of orbital radiotherapy.

Calibration of the channel that determines the omega-hydroxylation regiospecificity of cytochrome P4504A1 - Catalytic oxidation of 12-halododecanoic acids

The fatty acid omega-hydroxylation regiospecificity of CYP4 enzymes may result from presentation of the terminal carbon to the oxidizing species via a narrow channel that restricts access to the other carbon atoms. To test this hypothesis, the oxidation of 12-iodo-, 12-bromo-, and 12-chlorododecanoic acids by recombinant CYP4A1 has been examined. Although all three 12-halododecanoic acids bind to CYP4A1 with similar dissociation constants, the 12-chloro and 12-bromo fatty acids are oxidized to 12-hydroxydodecanoic acid and 12-oxododecanoic acid, whereas the 12-iodo analogue is very poorly oxidized. Incubations in (H2O)-O-18 show that the 12-hydroxydodecanoic acid oxygen derives from water, whereas that in the aldehyde derives from O-2. The alcohol thus arises from oxidation of the halide to an oxohalonium species that is hydrolyzed by water, whereas the aldehyde arises by a conventional carbon hydroxylation-elimination mechanism. No irreversible inactivation of CYP4A1 is observed during 12-halododecanoic acid oxidation. Control experiments show that CYP2E1, which has an omega-1 regiospecificity, primarily oxidizes 12-halododecanoic acids to the omega-aldehyde rather than alcohol product. Incubation of CYP4A1 with 12,12-[H-2](2)-12-chlorododecanoic acid causes a 2-3-fold increase in halogen versus carbon oxidation. The fact that the order of substrate oxidation (Br > Cl >> I) approximates the inverse of the intrinsic oxidizability of the halogen atoms is consistent with presentation of the halide terminus via a channel that accommodates the chloride and bromide but not iodide atoms, which implies an effective channel diameter greater than 3.90 angstrom but smaller than 4.30 angstrom.

Oral candidosis and the therapeutic use of antifungal agents in dentistry

This paper reviews the current concepts of mycology and candidal infections as they relate to the oral cavity. Proposed classification for the presentation of oral candidosis is outlined as are examples of these topical infections, such as erythematous, pseudomembranous and hyperplastic candidosis, as well as angular chelitis and median rhomboid glossitis. The diagnosis and principles of management of oral candidosis are discussed, the therapeutic agents available for the management of these infections are presented and a treatment protocol for the management of patients with oral candidosis is given.

Oral viral infections and the therapeutic use of antiviral agents in dentistry

This paper reviews the current concepts of viral classification, infection and replication. The clinical presentation of common oral viral infections encountered in the dental practice are discussed, including: herpes simplex virus types 1 and 2; Epstein-Barr virus; varicella-zoster virus; Coxsackie virus; human papilloma virus; and human immunodeficiency virus. The diagnosis, principles of management and pharmacological agents available for the treatment of oral viral infections are also discussed.