The role of dendritic cells in alphaherpesvirus infections: archetypes and paradigms

Dendritic cells (DCs) play a critical role in orchestrating both innate and adaptive components of the immune system and are therefore of pivotal importance in the initiation of immune responses to control and eliminate viral infections. A major focus of this review is to give an overview on the recent findings that point out the importance of DCs in controlling alphaherpesvirus infections, but also indicate that these viruses have evolved several strategies to inhibit and/or exploit DC functions to delay or escape elimination by the immune system. In addition, we point out the common features and interspecies differences between DCs from man and animal, and discuss the potential use of animal alphaherpesvirus homologues to gain further insights into the interaction between alphaherpesviruses and DCs in their natural virus–host environment. Finally, recent knowledge on the potential of alphaherpesviruses as vectors for DC stimulation and their use for immunotherapy is presented. Copyright © 2009 John Wiley & Sons, Ltd.     

Quantitative Changes of Sialoadhesin and CD163 Positive Macrophages in the Implantation Sites and Organs of Porcine Embryos/Fetuses During Gestation

Porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta most easily in the last third of gestation. Further, PRRSV does not replicate in preimplantation embryos but does replicate in postimplantation embryos and fetuses. In the present study, it was aimed to find an explanation for these observations by localization and quantification of the macrophages carrying two entry mediators that play a crucial role in PRRSV replication, sialoadhesin (Sn) and CD163, in the implantation sites and organs of embryos/fetuses during gestation. Uterus and embryos or organs (liver, spleen, lungs) from fetuses were obtained from pregnant PRRSV negative sows at different days of gestation (20–35, 50–60, 70–80, 114) and the Sn⁺ and CD163⁺ macrophages were quantified. In endometrium and placentas, two macrophage subsets were observed: Sn^?CD163⁺ and Sn⁺CD163⁺. The highest number of Sn⁺ and CD163⁺ macrophages was counted at 114 days of gestation. In the mid-gestation fetal placentas (50–60 days of gestation), most CD163⁺ macrophages were Sn negative. The number of Sn⁺ and CD163⁺ macrophages in organs increased during gestation. In the liver, the Sn⁺ and CD163⁺ macrophages were most abundant (Sn⁺: 8.1–48.7%; CD163⁺: 22.0–55.0%); the lowest number of Sn⁺ and CD163⁺ macrophages was observed in the lungs (Sn⁺: 0–15.2%; CD163⁺: 4.0–19.3%). Double immunofluorescence staining revealed three macrophage subsets in the spleen: Sn⁺CD163^?, Sn^?CD163⁺ and Sn⁺CD163⁺; and two macrophage subsets in the lungs: Sn^?CD163⁺ and Sn⁺CD163⁺. In the liver, due to physiological presence of biotin, the double immune-fluorescence staining could not be performed. The present results show clear changes in the quantity of Sn⁺ and CD163⁺ macrophages in the placentas and organs of embryos/fetuses during gestation which most probably have a physiological basis. The absence of Sn on macrophages in the fetal placenta at mid-gestation might explain the difficulty for PRRSV to spread transplacentally at this stage of gestation.     

Analysis of the relationship between age and treatment response in migraine

In migraine, headache severity varies with age. As a consequence, the effectiveness of medication may also depend on a patient's age. The purpose of this study was to assess the combined effect of age and drug treatment on headache characteristics. Using data from clinical trials of sumatriptan in adolescents and adults, we show how the interaction between age and drug exposure can be parameterised as a covariate on a Markov model that describes the decline of headache severity over three clinically defined stages (no relief, relief and pain-free status). The model explains important clinical observations: (i) the rates at which the pain relief and pain-free status were attained were found to be inversely related to age; (ii) in placebo-treated patients, the mean transit time from 'no relief' to 'relief' is 3 h for young adolescents and increases to 6 h for patients aged ≥ 30 years; and (iii) sumatriptan reduces the transit time to 2 h, irrespective of age. These findings indicate that the therapeutic gain over placebo increases with age. Prospective studies of antimigraine drugs should take this relationship into account when extrapolating efficacy data from adults to adolescents.     

Symptoms of ＂Heat＂ as a Pattern of Physiopathology

Objective： The guiding criteria are considered the backbone of Chinese medicine. They have previously been described as functional features （symptoms） leading to the overall assessment of human functions on the basis of a regulatory （cybernetic） model referring to the I Ging. Methods： The Heidelberg model can explain symptoms such as created by ＂heat＂ on a rational physiological level. Results ＆ Conclusion： The overall of physiological symptoms are shown as a schematic draft. The basis of ＂heat＂ is considered to be a general increase of microcirculation in the periphery. This leads to a couple of local pathophysiological consequences and sensations like 1） red tongue （the tongue is considered an embryological somatotopic system）. 2） Sensation of warmth （by increase of capillary flow）. 3） pre-inflammatory state, leading to pain modalities like ＂worse if pressed＂, as inflammations tend to be increasingly painful under pressure; 4） reddish skin, the mechanisms by which this is induced may include the release of substance P, therefore accompanied by burning sensation. Systemic pathophysiological consequences may include. Relative lack of fluid in the larger vessels, as fluid supplies peripheral capillary flow. This may lead to water saving mechanisms like thirst, dry mucosa with do, mouth, dry nose, dry lips, dry skin, and also dry stool, yellow and sparse urine.     

One-year audit of admissions to the Intensive Care Unit of the Queen Elizabeth Central Hospital,Blantyre

The intensive care unit at Queen Elizabeth Central Hospital (QECH) has 4 beds and offers level 2 care. A retrospective audit of all admissions to the unit during 2002 was carried out. There were a total of 339 admissions giving a bed occupancy rate of 82 %. Surgical patients made up 81 % of admissions. 45% of all admissions were ventilated. Overall mortality was 38%. Ventilated patients had a mortality of 71% compared with 10% for non-ventilated. Data are also presented for mortality within the surgical and paediatric surgical admissions.     

Use of E mu-PIM-1 transgenic mice short-term in vivo carcinogenicity testing: lymphoma induction by benzo[a]pyrene, but not by TPA

E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to their low spontaneous tumour incidence and their increased sensitivity towards the lymphomagen ethylnitrosourea these mice may present an interesting model for short-term carcinogenicity testing. Here, we report on the further exploration of this transgenic mouse model with two additional carcinogens known to have, among others, the lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and 12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week (by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1 mice during the observation period of 40 weeks. B[a]P also induced tumours of the forestomach within this observation period, though at a lower incidence and apparently equally effective in wildtype and transgenic mice. TPA, on the other hand, was unable to induce lymphomas (or tumours in any other organ) in either transgenic or wildtype animals within the observation period of 44 weeks, when applied dermally at the maximum tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular analysis showed that B[a]P-induced lymphomas in transgenic mice were of T-cell origin, 80% of which had elevated levels of c-myc expression. None of the lymphomas had increased N-myc expression and mutation analysis of the ras-gene family revealed a K-ras mutation in only one out of eight tumours investigated. Also, none of the lymphomas showed aberrant expression of p53 as determined by immunohistochemistry. It is concluded that the E mu-pim-1 mouse model will not be very suitable for short-term carcinogenicity testing in general: only genotoxic chemicals that have the lymphohaematopoietic system as target for carcinogenesis in wild- type mice, appear to be efficiently identified.      

Localized muscular mucormycosis in a child with acute leukemia

Mucormycosis is a rare fungal infection of childhood, occurring mainly in patients with chronic illnesses such as diabetes and malignancies. The fungus seldom grows in culture and confirmation of the diagnosis depends on histologic examination of infected tissues. To date, the reported natural history of the disease has been rapid progression and a fatal outcome. Therefore, the importance of early diagnosis by tissue biopsy and early treatment with surgical debridement and systemic antifungal therapy cannot be overemphasized. The pulmonary system is the most common site for mucormycosis in patients with leukemia. We report what we believe to be the first successfully treated case of isolated muscular mucormycosis occurring in a child with biphenotypic acute leukemia. The diagnosis was made promptly by tissue examination at the time of surgical debridement. The patient was also given systemic amphotericin-B therapy.      

Standards for total body fat and fat-free mass in infants

Data on body composition in conjunction with reference centiles are helpful in identifying the severity of growth and nutritional disorders in infancy and for evaluating the adequacy of treatment given during this important period of rapid growth. Total body fat (TBF) and fat-free mass (FFM) were estimated from total body electrical conductivity (TBEC) measurements in 423 healthy term Caucasian infants, aged 14-379 days. Cross sectional age, weight, and length related centile standards are presented for TBF and FFM. Centiles were calculated using Altman's method, based on polynomial regression and modelling of the residual variation. The TBF percentage steeply increased during the first half year of life, and slowly declined beyond this age. Various simple TBEC derived anthropometric prediction equations for TBF and FFM are available to be used in conjunction with these standards. Regression equations for the P50 and the residual SD, depending on age, weight, or length, are provided for constructing centile charts and calculating standard deviation scores.