Biomedical subjects

A Bernard

Publications and source records attributed to A Bernard.

At least 55 records · Page 3Linked to original sources

PubMed2001

Vav2 activates c-fos serum response element and CD69 expression but negatively regulates nuclear factor of activated T cells and interleukin-2 gene activation in T lymphocyte.

Vav1 and Vav2 are members of the Dbl family of guanine nucleotide exchange factors for the Rho family of small GTPases. Although the role of Vav1 during lymphocyte development and activation is well characterized, the function of Vav2 is still unclear. In this study, we compared the signaling pathways regulated by Vav1 and Vav2 following engagement of the T cell receptor (TCR). We show that Vav2 is tyrosine-phosphorylated upon TCR stimulation and by co-expressed Src and Syk family kinases. Using glutathione S-transferase fusion proteins, we observed that the Src homology 2 domain of Vav2 binds tyrosine-phosphorylated proteins from TCR-stimulated Jurkat T cell lysates, including c-Cbl and SLP-76. Like Vav1, Vav2 cooperated with TCR stimulation to increase extracellular signal-regulated kinase activation and to promote c-fos serum response element transcriptional activity. Moreover, both proteins displayed a similar action in increasing the expression of the early activation marker CD69 in Jurkat T cells. However, in contrast to Vav1, Vav2 dramatically suppressed TCR signals leading to nuclear factor of activated T cells (NF-AT)-dependent transcription and induction of the interleukin-2 promoter. Vav2 appears to act upstream of the phosphatase calcineurin because a constitutively active form of calcineurin rescued the effect of Vav2 by restoring TCR-induced NF-AT activation. Interestingly, the Dbl homology and Src homology 2 domains of Vav2 were necessary for its inhibitory effect on NF-AT activation and for induction of serum response element transcriptional activity. Taken together, our results indicate that Vav1 and Vav2 exert overlapping but nonidentical functions in T cells. The negative regulatory pathway elicited by Vav2 might play an important role in regulating lymphocyte activation processes.

Antigens, CD↗

PubMed2001

Micromosaic immunoassays.

Immunoassays are widely used for medical diagnostics and constitute the principal method of detecting pathogenic agents and thus of diagnosing many diseases. These assays, which are most often performed in well plates, would be greatly improved by a practical method to pattern a series of antigens on a flat surface and to localize their binding to many analytes. But no obvious method exists to expose a planar surface successively to a series of antigens and analytes. Here, we present miniaturized mosaic immunoassays based on patterning lines of antigens onto a surface by means of a microfluidic network (muFN). Solutions to be analyzed are delivered by the channels of a second muFN across the pattern of antigens. Specific binding of the target antibodies with their immobilized antigens on the surface results in a mosaic of binding events that can readily be visualized in one screening using fluorescence. It is thus possible to screen solutions for antibodies in a combinatorial fashion with great economy of reagents and at a high degree of miniaturization. Such mosaic-format immunoassays are compatible with the sensitivity and reliability required for immunodiagnostic methods.

Enzyme-Linked Immunosorbent Assay↗

PubMed2001

Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia.

PURPOSE: In patients with neutropenia, thoracic computed tomography (CT) halo and air-crescent signs are recognized as major indicators of invasive pulmonary aspergillosis (IPA). Nevertheless, the exact timing of CT images is not well known. PATIENTS AND METHODS: Seventy-one thoracic CT scans were analyzed in 25 patients with neutropenia with surgically proven IPA. RESULTS: On the first day of IPA diagnosis with early CT scan (d0), a typical CT halo sign was observed in 24 of 25 patients. At that time, the median number of thoracic lesions was two (range, one to six), and pulmonary involvement was bilateral in 12 cases. The halo sign was present in 68%, 22%, and 19% of cases on d3, d7, and d14, respectively. Similarly, the air-crescent sign was seen in 8%, 28%, and 63% of cases on the same days. Otherwise, a nonspecific air-space consolidation aspect was seen in 31%, 50%, and 18% of cases on the same days. The analysis of calculated aspergillary volumes on CT showed that, despite antifungal treatment, the median volume of lesions increased four-fold from d0 to d7, whereas it remained stable from d7 to d14. Overall, 21 patients (84%) were cured by the medical-surgical approach. CONCLUSION: In patients with neutropenia, CT halo sign is a highly effective modality for IPA diagnosis. The duration of the halo sign is short, and it demonstrates the value of early CT. The increase of the aspergillosis size on CT in the first days after IPA diagnosis is not correlated with a pejorative immediate outcome when using a combined medical-surgical approach.

Adolescent↗

PubMed2001

Measurements of resistance by the interrupter technique and of transcutaneous partial pressure of oxygen in young children during methacholine challenge.

Measurement of bronchial airway responsiveness requires noninvasive techniques in young children. The study was designed to examine the changes in resistance as measured using the interrupter technique (Rint) at the dose of methacholine (M) that induced a fall in transcutaneous partial pressure in O2 (P(tc)O2) > or = 20% (PD(20)P(tc)O2) in young children. Rint was calculated using the linear back-extrapolation method (Rint(L)) and the end-interrupter method (Rint(EI)). Twenty-two children (mean age, 5.2 +/- 1.1 years; range, 3.4 - 7.1 years) with nonspecific respiratory symptoms (mainly chronic cough, n = 17) were tested. P(tc)O2, Rint(L), and Rint(EI) were measured before the test, after saline challenge (baseline (B)), after each dose of M delivered by a dosimeter, and after bronchodilator (BD) inhalation. P(tc)O2 decreased significantly during M challenge, from 85 +/- 6 mmHg (B) to 62 +/- 9 mmHg (P < 0.05), and increased after BD inhalation, to 82 +/- 8 mmHg. Rint(L) and Rint(EI) increased significantly during M challenge, from 0.94 +/- 0.2 KPa/L/s and 1.11 +/- 0.19 KPa/L/s (B) to 1.27 +/- 0.35 KPa/L/s and 1.47 +/- 0.37 KPa/L/s, respectively (P < 0.05), and decreased after BD inhalation to 0.80 +/- 0.17 KPa/L/s and 0.95 +/- 0.18 KPa/L/s, respectively. Nineteen of 22 children reached the PD(20)P(tc)O2 at a dose of M ranging from 50-400 microg. At the PD(20)P(tc)O2, significant changes in Rint(L) and Rint(EI) (sensitivity index (SI) > or = 2) were found in 79% and 63% of children, respectively. We conclude that: 1) M challenge using P(tc)O2 is safe in young children; and 2) our findings are not in favor of the use of Rint as the only indicator of bronchial reaction in young children during M challenge.

Airway Resistance↗

PubMed2001

Cardiac pheochromocytoma.

Primary pheochromocytomas of the heart are extremely uncommon. In this report, we present the case of a patient with primary cardiac pheochromocytoma arising from the interatrial septum. Metaiodobenzylguanidine-scintigraphy was negative and diagnosis was confirmed by a positive octreotide scintiscan. The tumor was removed successfully using cardiopulmonary bypass.

3-Iodobenzylguanidine↗

PubMed2001

Resection of adrenal metastases from non-small cell lung cancer: a multicenter study.

BACKGROUND: In recent case reports and limited series, adrenalectomy was recommended for an isolated adrenal metastasis from non-small cell lung cancer (NSCLC). METHODS: We retrospectively studied patients with a solitary adrenal metastasis from NSCLC who had undergone potentially curative resection in eight centers. RESULTS: Forty-three patients were included. Their adrenal gland metastasis was discovered synchronously with NSCLC in 32 patients, and metachronously in 11. It was homolateral to the NSCLC in 31 patients and contralateral in 12 (p < 0.01). Median survival was 11 months, and 3 patients survived more than 5 years. There was no difference between the synchronous and metachronous groups regarding recurrence rate or survival. Survival was not affected by the homolateral location of the metastasis, the histology of the NSCLC, TNM stage, any adjuvant and neoadjuvant treatment, or, in the metachronous group, a disease-free interval exceeding 6 months. CONCLUSIONS: We confirm the possibility of long-term survival after resection of isolated adrenal metastasis from NSCLC, but no clinical or pathologic criteria were detected to identify patients amenable to potential cure.

Adrenal Gland Neoplasms↗

PubMed2001

Empyema and bronchopleural fistula after pneumonectomy: factors affecting incidence.

BACKGROUND: Factors affecting the incidence of empyema and bronchopleural fistula (BPF) after pneumonectomy were analyzed. METHODS: All patients who underwent pneumonectomy at the Mayo Clinic in Rochester, Minnesota, from January 1985 to September 1998 were reviewed. There were 713 patients (514 males and 199 females). Ages ranged from 12 to 86 years (median 64 years). Indication for resection was primary malignancy in 607 patients (85.1%), metastatic disease in 32 (4.5%), and benign disease in 74 (10.4%). One hundred fifteen patients (16.1%) underwent completion pneumonectomy. Factors affecting the incidence of postoperative empyema and BPF were analyzed using univariate and multivariate analysis. RESULTS: Empyema was documented in 53 patients (7.5%; 95% confidence interval [CI], 5.7% to 9.7%) and a BPF in 32 (4.5%; 95% CI, 3.1% to 6.3%). Univariate analysis demonstrated that the development of empyema was adversely affected by benign disease (p = 0.0001), lower preoperative forced expiratory volume in 1 second (FEV1; p < 0.01) and diffusion capacity of lung to carbon monoxide (DLCO; p = 0.0001), lower preoperative serum hemoglobin (p = 0.05), right pneumonectomy (p = 0.0109), bronchial stump reinforcement (p = 0.007), completion pneumonectomy (p < 0.01), timing of chest tube removal (p = 0.01), and the amount of blood transfusions (p < 0.01). Similarly, the development of BPF was significantly associated with benign disease (p = 0.03), lower preoperative FEV1 (p = 0.03) and DLCO (p = 0.01), right pneumonectomy (p < 0.0001), bronchial stump reinforcement (p = 0.03), timing of chest tube removal (p = 0.004), increased intravenous fluid in the first 12 hours (p = 0.04), and blood transfusions (p = 0.04). Bronchial stump closure with staples had a protective effect against BPF compared with suture closure (p = 0.009). No risk factors were identified as being jointly significant in multivariate analysis. CONCLUSIONS: Multiple perioperative factors were associated with an increased incidence of empyema and BPF after pneumonectomy. Prophylactic reinforcement of the bronchial stump with viable tissue may be indicated in those patients suspected at higher risk for either empyema or BPF.

Adolescent↗

PubMed2001

[Recombinant hirudin in neurosurgery].

We report the case of a 70-year-old woman with paraplegia resulting from spinal cord compression secondary to an epidural haematoma. Because of an arrhythmia, a mitral valve replacement and the high risk of venous thrombosis, an anticoagulant treatment was introduced postoperatively. The patient having previously developed an type II heparin-induced thrombocytopaenia, a treatment by lepirudine was established successfully.

Aged↗

PubMed2001

Risk analysis and long-term survival in patients undergoing resection of T4 lung cancer.

OBJECTIVE: The aim of this study is to identify the risk group of patients with T4 lung cancer who could more likely benefit from surgical resection. METHODS: Between January 1, 1990, and December 31, 1998, 77 patients underwent pulmonary resection for T4 lung cancer: lobectomy (n = 20), bilobectomy (n = 4) and pneumonectomy (n = 53). The T4 sites of mediastinal involvement were: Intrapericardiac portions of the pulmonary artery (n = 30), left atrium (n = 19), aorta (n = 8), superior vena cava (n = 8), carina (n = 7), the esophagus (n = 8) and the vertebral body (n = 6). Ten patients had multiple neoplastic nodules in the same lobe of the lung. RESULTS: Overall survival rates at 1, 2 and 3 years were 46, 31 and 21%, respectively. Factors adversely affecting survival with univariate analysis included the localization of tumours in the lower lobe (P = 0.04) and both the involvement of superior and inferior mediastinal lymph nodes (P = 0.03). Multivariate analysis included two factors adversely affecting survival: the location of the primary tumour and the nodal stations involved. Regression tree analysis classified the patients into low-risk group (primary tumour in upper lobe or in main stem bronchus and pN0 or pN1 or superior or inferior mediastinal nodes involved), intermediate-risk group (primary tumour in upper lobe or in main stem bronchus and both superior and inferior mediastinal nodes involved, primary tumour in inferior lobe and pN0 or pN1 or inferior mediastinal nodes involved) and high-risk group (primary tumour in inferior lobe and both superior and inferior nodes involved). The 3-year survival rates were 36% for the low-risk group, 4% for the intermediate-risk group and 0% for the high-risk group (P = 0.006). CONCLUSIONS: In patients with T4 lung cancer, the surgery can justify itself for tumours in the upper lobe or in the main stem bronchus and with pN0 or pN1.

Adult↗

PubMed2001

Affinity capture of proteins from solution and their dissociation by contact printing.

Biological experiments at the solid/liquid interface, in general, require surfaces with a thin layer of purified molecules, which often represent precious material. Here, we have devised a method to extract proteins with high selectivity from crude biological sample solutions and place them on a surface in a functional, arbitrary pattern. This method, called affinity-contact printing (alphaCP), uses a structured elastomer derivatized with ligands against the target molecules. After the target molecules have been captured, they are printed from the elastomer onto a variety of surfaces. The ligand remains on the stamp for reuse. In contrast with conventional affinity chromatography, here dissociation and release of captured molecules to the substrate are achieved mechanically. We demonstrate this technique by extracting the cell adhesion molecule neuron-glia cell adhesion molecule (NgCAM) from tissue homogenates and cell culture lysates and patterning affinity-purified NgCAM on polystyrene to stimulate the attachment of neuronal cells and guide axon outgrowth.

Animals↗

PubMed2001

Amniotic fluid Clara cell protein concentration in normal pregnancy, a marker of fetal airway growth or fetal lung maturation?

OBJECTIVE: To evaluate the relationship of Clara cell protein (CCP) in amniotic fluid (AF) with the lecithin/sphingomyelin (L/S) ratio, and the concentrations of saturated phosphatidylcholine (Sat PC) and surfactant protein A (SP-A). STUDY DESIGN: AF samples were obtained by amniocentesis from 98 pregnancies without conditions known to influence fetal lung maturation between 25 and 41 weeks of gestation. These samples were used for determinations of CCP, L/S ratio, Sat PC, and SP-A. Simple and multiple linear regressions were used to analyze the data. RESULTS: CCP in AF increased logarithmically with gestational age (R(2)=0.51, p=0.006). The L/S ratio (R(2)=0.41, p<0.001), and the concentrations of Sat PC (R(2)=0.26, p<0.001) and SP-A (R(2)=0.52, p<0.001) also increased with advancing gestation. Weak correlations of CCP with the L/S ratio (R(2)=0.22, p=0.009) and Sat PC (R(2)=0.12, p=0.004), but not with SP-A (R(2)=0.07, p=0.10), were found. Using multiple linear regressions, gestational age was the only predictor of CCP (F=10.9, R(2)=0.13, p=0.015). Conversely, gestational age, Sat PC, and SP-A accounted for most of the variation of the L/S ratio (F=34.7, R(2)=0.61, p=0.0001). CONCLUSION: CCP correlated very poorly with known and widely accepted indices of fetal lung maturation. The increasing concentration of CCP in AF throughout gestation probably reflects growth and development of the fetal airways.

Amniotic Fluid↗

PubMed2001

Tyrosine phosphorylation of ionotropic glutamate receptors by Fyn or Src differentially modulates their susceptibility to calpain and enhances their binding to spectrin and PSD-95.

Both tyrosine phosphorylation and calpain-mediated truncation of ionotropic glutamate receptors are important mechanisms for synaptic plasticity. Previous work from our laboratory has shown that calpain activation results in truncation of the C-terminal domains of several glutamate receptor subunits. To test whether and how tyrosine phosphorylation of glutamate ionotropic receptor subunits modulates calpain susceptibility, synaptic membranes were phosphorylated by Fyn or Src, two members of the Src family tyrosine kinases. Tyrosine phosphorylation of synaptic membranes by Src significantly reduced calpain-mediated truncation of both NR2A and NR2B subunits of NMDA receptors, but not of GluR1 subunits of AMPA receptors. In contrast, phosphorylation with Fyn significantly protected calpain-mediated truncation of GluR1 subunits of AMPA receptors, but enhanced calpain-mediated truncation of NR2A subunits of NMDA receptors. Similar results were observed with NR2A and NR2B C-terminal domain fusion proteins phosphorylated by Fyn or Src before incubation with calpain and calcium. In addition, phosphorylation of NR2A and NR2B C-terminal fusion proteins by Fyn or Src enhanced their binding to spectrin and PSD-95. Thus, tyrosine phosphorylation impairs or facilitates calpain-mediated truncation of glutamate receptor subunits, depending on which tyrosine kinase is activated. Such mechanisms could serve to regulate receptor integrity and location, in addition to modulating channel properties.

Animals↗

PubMed2001

Pneumonectomy for malignant disease: factors affecting early morbidity and mortality.

OBJECTIVE: The purpose of this report is to analyze factors affecting morbidity and mortality after pneumonectomy for malignant disease. METHODS: We retrospectively reviewed the cases of all patients who underwent pneumonectomy for malignancy at the Mayo Clinic. Between January 1, 1985, and September 30, 1998, 639 patients (469 men and 170 women) were identified. Median age was 64 years (range 20 to 86 years). Indication for pneumonectomy was primary lung cancer in 607 (95.0%) patients and metastatic disease in 32 (5.0%). Factors affecting morbidity and mortality were analyzed by univariate and multivariate analysis. RESULTS: Cardiopulmonary complications occurred in 245 patients (38.3%; 95% confidence interval 34.6%-42.2%). Factors adversely affecting morbidity with univariate analysis included age (P <.0001), male sex (P =.04), associated respiratory (P =.02) or cardiovascular disease (P <.0001), cigarette smoking (P =.02), decreased vital capacity (P =.01), forced expiratory volume in 1 second (P <.0001), forced vital capacity (P =.002), diffusion capacity of the lung to carbon monoxide (P =.005), oxygen saturation (P <.05), arterial PO (2) (P =.007), preoperative radiation (P =.02), bronchial stump reinforcement (P =.007), crystalloid infusion (P =.01), and blood transfusion (P =.02). Factors adversely affecting morbidity with multivariate analysis included age (P =.0001), associated cardiovascular disease (P =.001), and bronchial stump reinforcement (P =.0005). There were 45 deaths (7.0%; 95% confidence intervals 5.2%-9.3%). Factors adversely affecting mortality with univariate analysis included associated cardiovascular (P <.0001) or hematologic disease (P <.005), lower preoperative serum hemoglobin level (P =.004), preoperative chemotherapy (P =.01), decreased diffusion capacity of lung to carbon monoxide (P =.002), right pneumonectomy (P =.0006), extended resection (P =.04), bronchial stump reinforcement (P =.007), and crystalloid infusion (P =.01). Factors affecting mortality with multivariate analysis included hematologic disease (P =.01), lower preoperative serum hemoglobin (P =.003), and completion pneumonectomy (P =.01). CONCLUSION: Multiple factors adversely affected morbidity and mortality after pneumonectomy for malignant disease. Appropriate selection and meticulous perioperative care are paramount to minimize risks in those patients who require pneumonectomy.

Adult↗

PubMed2001

Persistent viral load in patients on HAART is associated with a higher level of activation-induced apoptosis of CD4(+) T cells.

Apoptosis is one of the mechanisms involved in the persistent CD4(+) T cell lymphopenia occurring in human immunodeficiency virus (HIV)-infected patients treated with highly active antiretroviral therapy (HAART). The aim of this study was to look at the relationship between the level of T cell apoptosis in patients on HAART and their HIV viral load measurement. Forty-five patients receiving HAART for a median time of 5 months were included: 13 had an undetectable viral load and 32 had a viral load > or = 200 copies/mL. No relationship was observed between the level of spontaneous T cell apoptosis and the viral load measurement. Patients with a viral load > or = 200 copies/mL exhibited a significantly higher level of CD4-induced apoptosis of CD4(+) T cells, compared with patients with undetectable viraemia (38 versus 15%, respectively, P = 0.03). Activation-induced apoptosis may be involved in the paucity of the immune reconstitution observed in HIV-infected patients treated with HAART.

Adult↗

PubMed2001

New approach for accurate simulation of human pharmacokinetics in an in vitro pharmacodynamic model: application to ciprofloxacin.

An in vitro pharmacodynamic model using a disposable dialyser unit and computer-controlled devices was developed. Feedback control of peristaltic pump flow rates is used to maintain constant flow rates, thus avoiding the problem of the modification of the physical properties of the tubing that generally occurs. Fast equilibrium is obtained with capillaries, which allows simulation of the same kinetic profile in the central and the peripheral compartments. Thus, more accurate simulation of plasma, extracapillary fluid or whole tissue kinetics can be performed. Our model was validated by simulation of a 30 min infusion of a 200 mg dose, and of an oral administration of a 500 mg dose of ciprofloxacin.

Administration, Oral↗

PubMed2001

Integrin-associated protein (CD47/IAP) contributes to T cell arrest on inflammatory vascular endothelium under flow.

Integrin-associated protein (CD47/IAP) is a pentaspan molecule that regulates integrin functions. We prepared a CD47-deficient Jurkat T cell line to assess its role in the arrest of T cells on inflammatory endothelium. Under flow conditions, constitutive arrest of CD47-deficient cells is strongly decreased as compared to the original cell line, whereas reexpression of CD47 reestablishes their ability to stop. Moreover, cells transfected with a chimera made with the extracellular portion of CD47 and the transmembrane domain of CD7 or several truncated forms of CD47 show that the first transmembrane domain and a short cytoplasmic loop are sufficient for this process. CD47 effect is indirect and depends mainly on the alpha4beta1/VCAM-1 pathway, as shown by blocking antibodies. We detected on endothelium the two CD47 counter receptors known to date: thrombospondin and SIRP1alpha. Blocking experiments show that both are involved. Overall, CD47 participates in the constitutive arrest of T lymphocytes on inflamed vascular endothelium by up-regulating alpha 4beta1 integrins.

Antibodies, Monoclonal↗

PubMed2001

Analysis of nitric oxide activity in prevention of reperfusion injury.

This project was designed to determine the role of nitric oxide (NO) in the prevention of ischemia-reperfusion injury. Inferiorly based rectus abdominis muscle flaps were elevated in pigs and subjected to 6 hours of ischemia followed by 4 hours of reperfusion. Group I animals received a bolus of L-arginine before reperfusion, and a continuous infusion once flow was restored. Group II animals served as controls and received an equal volume of saline as a bolus and subsequent continuous infusion. Microdialysis was used to measure tissue NO levels, and these were correlated with muscle survival determined by vital staining with nitroblue tetrazolium. The results demonstrated a significant increase in tissue NO levels in L-arginine-supplemented animals (p < 0.05), which in turn correlated with a significant increase in muscle survival (p = 0.0051). These results suggest that administration of supplemental L-arginine to ischemic skeletal muscle during reperfusion results in increased NO production and decreased tissue damage.

Animals↗

PubMed2001

Morbillivirus infection of the mouse central nervous system induces region-specific upregulation of MMPs and TIMPs correlated to inflammatory cytokine expression.

Viral infection of the central nervous system (CNS) can result in perturbation of cell-to-cell communication involving the extracellular matrix (ECM). ECM integrity is maintained by a dynamic balance between the synthesis and proteolysis of its components, mainly as a result of the action of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). An MMP/TIMP imbalance may be critical in triggering neurological disorders, in particular in virally induced neural disorders. In the present study, a mouse model of brain infection using a neurotropic strain of canine distemper virus (CDV) was used to study the effect of CNS infection on the MMP/TIMP balance and cytokine expression. CDV replicates almost exclusively in neurons and has a unique pattern of expression (cortex, hypothalamus, monoaminergic nuclei, hippocampus, and spinal cord). Here we show that although several mouse brain structures were infected, they exhibited a differential pattern in terms of MMP, TIMP, and cytokine expression, exemplified by (i) a large increase in pro-MMP9 levels, in particular in the hippocampus, which occurred mainly in neurons and was associated with in situ gelatinolytic activity, (ii) specific and significant upregulation of MT1-MMP mRNA expression in the cortex and hypothalamus, (iii) an MMP/TIMP imbalance, suggested by the upregulation of TIMP-1 mRNA in the cortex, hippocampus, and hypothalamus and of TIMP-3 mRNA in the cortex, and (iv) a concomitant region-specific large increase in expression of Th1-like cytokines, such as gamma interferon, tumor necrosis factor alpha, and interleukin 6 (IL-6), contrasting with weaker induction of Th2-like cytokines, such as IL-4 and IL-10. These data indicate that an MMP/TIMP imbalance in specific brain structures, which is tightly associated with a local inflammatory process as shown by the presence of immune infiltrating cells, differentially impairs CNS integrity and may contribute to the multiplicity of late neurological disorders observed in this viral mouse model.

Animals↗