Common Law Liability of the Certified Public Accountant for Negligent Misrepresentation

This Article explores the scope of the duty owed by an accountant for negligent misrepresentation as articulated in the Supreme Court\u27s holding in Ultramares v. Touche. He begins by reviewing accounting standards governing accountants in performing a certified audit. He examines the Court\u27s holding in Ultramares, the policy considerations upon which the decision was based, the cases that follow it, and those cases which reject it. The author questions the Court\u27s holding that an accountant\u27s duty is limited to those with whom he is in privity, and argues that social, economic, and legal considerations now require accountants to be judged by the same standards applied to other professionals, and should be held liable for any reasonably foreseeable harm caused by their negligence

Identification of Cytolytic CD161−^−CD56+^+ Regulatory CD8 T Cells in Human Peripheral Blood

We previously developed methods for establishing CD8 regulatory T cell (Treg) clones from normal human peripheral blood and demonstrated that these clones were capable of killing T cell receptor (TCR)-activated autologous CD4 T cells. Based on phenotypic and functional characterization of the CD8 Treg clones, we have identified a corresponding population of endogenous CD8 Treg in normal human peripheral blood. These cells appear morphologically as large lymphocytes with abundant cytoplasm and have the following unique phenotype: CD3$^+$CD8$^+$CD161$^−$CD56$^+$. The majority of CD8 Treg express CD45RA and CD62L with low or negative expression of CD45RO, CD25, CD27, CD28 and CCR7. The expression of CD94 and NKG2a on CD8 Treg was elevated compared to conventional CD8 T cells. Following in vitro activation, this T cell subset is capable of killing TCR-activated CD4 T cells. These studies identify an endogenous CD8 Treg population in humans and it will now be possible to characterize these cells in a variety of clinical conditions

Induction of Immunological Tolerance by Oral Anti-CD3

In recent years, our knowledge about immunoregulation and autoimmunity has significantly advanced, but nontoxic and more effective treatments for different inflammatory and autoimmune diseases are still lacking. Oral tolerance is of unique immunologic importance because it is a continuous natural immunologic event driven by exogenous antigen and is an attractive approach for treatment of these conditions. Parenteral administration of anti-CD3 monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. Orally administered anti-CD3 monoclonal antibody is biologically active in the gut and suppresses experimental models of autoimmune diseases. Orally delivered antibody does not have side effects including cytokine release syndromes, thus oral anti-CD3 antibody is clinically applicable for chronic therapy. Here we review findings that identify a novel and powerful immunologic approach that is widely applicable for the treatment of human autoimmune conditions

Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-β) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy

Neoangiogenesis and Blood-brain Barrier Dysfunction in Human TSC Brain Lesions

Introduction: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the presence of multiple benign tumors throughout the body and brain. Patients with TSC experience severe cognitive dysfunction and therapy-resistant seizures, which can be associated with refractory epilepsy and poor developmental outcomes. We hypothesize that neoangiogenesis, disruption of the blood-brain barrier, and leakage of serum proteins into the brain parenchyma play vital roles in the pathogenesis of TSC. Methods: In order to assess blood-brain barrier integrity, cortical tissue samples from TSC patients with intractable seizures, non-TSC patients with therapy-resistant epilepsy, and control subjects were immunolabeled for the serum protein fibrinogen, the adherens junction protein V-cadherin, and the tight junction protein occludin. Lectin was used to visualize blood vessels. Quantification was performed to assess average blood vessel segment length and branching. The fraction of membrane-associated V-cadherin and occludin, relative to the blood vessel surface area represented by lectin, was also analyzed. Results: The average length of blood vessel segments and the average number of branch nodes were significantly increased in TSC compared to epilepsy and control. The average surface area fraction of V-cadherin and occludin was significantly decreased in TSC compared to control. In addition, fibrinogen staining outside of the blood vessels was extensive in both TSC and epilepsy. These results confirm our hypothesis, suggesting blood-brain barrier dysfunction in TSC, with disease-specific neoangiogenic mechanisms in TSC. Discussion: Our results show increased blood-brain barrier permeability and increased vascular proliferation in TSC. These findings are likely due to decreased expression of tight junctions and adherens junctions in TSC cortical tissue. These results suggest that antiangiogenic therapies targeting the blood-brain barrier may offer a novel approach to preventing epileptogenesis in patients with TSC

Variations of the ISM Compactness Across the Main Sequence of Star-Forming Galaxies: Observations and Simulations

(abridged) The majority of star-forming galaxies follow a simple empirical correlation in the star formation rate (SFR) versus stellar mass ($M_*$) plane, usually referred to as the star formation Main Sequence (MS). Here we combine a set of hydro-dynamical simulations of interacting galactic disks with state-of-the-art radiative transfer codes to analyze how the evolution of mergers is reflected upon the properties of the MS. We present \textsc{Chiburst}, a Markov Chain Monte Carlo (MCMC) Spectral Energy Distribution (SED) code that fits the multi-wavelength, broad-band photometry of galaxies and derives stellar masses, star formation rates, and geometrical properties of the dust distribution. We apply this tool to the SEDs of simulated mergers and compare the derived results with the reference output from the simulations. Our results indicate that changes in the SEDs of mergers as they approach coalescence and depart from the MS are related to an evolution of dust geometry in scales larger than a few hundred parsecs. This is reflected in a correlation between the specific star formation rate (sSFR), and the compactness parameter $\mathcal{C}$, that parametrizes this geometry and hence the evolution of dust temperature ($T_{\rm{dust}}$) with time. As mergers approach coalescence, they depart from the MS and increase their compactness, which implies that moderate outliers of the MS are consistent with late-type mergers. By further applying our method to real observations of Luminous Infrared Galaxies (LIRGs), we show that the merger scenario is unable to explain these extreme outliers of the MS. Only by significantly increasing the gas fraction in the simulations are we able to reproduce the SEDs of LIRGs.Comment: 18 pages, 10 figures, accepted in Ap

Resistance to Experimental Autoimmune Encephalomyelitis in Mice Lacking the Cc Chemokine Receptor (Ccr2)

Monocyte recruitment to the central nervous system (CNS) is a necessary step in the development of pathologic inflammatory lesions in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Monocyte chemoattractant protein (MCP)-1, a potent agonist for directed monocyte migration, has been implicated in the pathogenesis of EAE. Here we report that deficiency in CC chemokine receptor (CCR)2, the receptor for MCP-1, confers resistance to EAE induced with a peptide derived from myelin oligodendrocyte glycoprotein peptide 35–55 (MOGp35–55). CCR2−/− mice immunized with MOGp35–55 failed to develop mononuclear cell inflammatory infiltrates in the CNS and failed to increase CNS levels of the chemokines RANTES (regulated on activation, normal T cell expressed and secreted), MCP-1, and interferon (IFN)-inducible protein 10 (IP-10) as well the chemokine receptors CCR1, CCR2, and CCR5. Additionally, T cells from CCR2−/− immunized mice showed decreased antigen-induced proliferation and production of IFN-γ compared with wild-type immunized controls, suggesting that CCR2 enhances the T helper cell type 1 immune response in EAE. These data indicate that CCR2 plays a necessary and nonredundant role in the pathogenesis of EAE

Effect of Natalizumab Treatment on Circulating Plasmacytoid Dendritic Cells: A Cross-Sectional Observational Study in Patients with Multiple Sclerosis

Objectives: Dendritic cells (DCs) serve a critical role both in promoting and inhibiting adaptive immunity. The goal of this study was to investigate the effect of natalizumab (NTZ) treatment on DC numbers, phenotype, and function in patients with multiple sclerosis (MS). Methods: Frequency and phenotype of myeloid and plasmacytoid DCs (MDCs and PDCs, respectively) were analyzed in blood from two separate cohorts of untreated, interferon-treated, or NTZ-treated MS patients. In addition, PDCs were stimulated with CpG-containing oligonucleotides or co-cultured with homologous T cells in the presence or absence of NTZ in vitro to determine functional effects of NTZ treatment. Results: We observed that NTZ treatment was associated with a 25–50% reduction in PDC frequency in peripheral blood as compared to untreated MS patients, while the frequency of MDCs was unchanged. PDCs in NTZ-treated patients displayed a mature, activated phenotype with increased expression of HLA-DR, TLR9, CCR7, IL-6 and IL-12. In contrast, in vitro treatment with NTZ did not increase markers of PDC activation or their ability to induce T cell differentiation. Conclusion: Our study shows that NTZ treatment is associated with a reduced frequency of PDCs in the peripheral circulation, but that PDCs in NTZ-treated individuals display an activated phenotype. Taken together the data suggests that transmigration of activated PDCs is preferentially affected by blockade of integrin α4 leading to an increased frequency of activated PDCs in blood