High-Precision Measurement of the Proton's Atomic Mass.

We report on the precise measurement of the atomic mass of a single proton with a purpose-built Penning-trap system. With a precision of 32 parts per trillion our result not only improves on the current CODATA literature value by a factor of 3, but also disagrees with it at a level of about 3 standard deviations.

Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor.

The mechanisms underlying the hepatotropism of hepatitis A virus (HAV) and the relapsing courses of HAV infections are unknown. In this report, we show for a mouse hepatocyte model that HAV-specific immunoglobulin A (IgA) mediates infection of hepatocytes with HAV via the asialoglycoprotein receptor, which binds and internalizes IgA molecules. Proof of HAV infection was obtained by detection of HAV minus-strand RNA, which is indicative for virus replication, and quantification of infectious virions. We demonstrate that human hepatocytes also ingest HAV-anti-HAV IgA complexes by the same mechanism, resulting in infection of the cells, by using the HepG2 cell line and primary hepatocytes. The relevance of this surrogate receptor mechanism in HAV pathogenesis lies in the fact that HAV, IgA, and antigen-IgA complexes use the same pathway within the organism, leading from the gastrointestinal tract to the liver via blood and back to the gastrointestinal tract via bile fluid. Therefore, HAV-specific IgA antibodies produced by gastrointestinal mucosa-associated lymphoid tissue may serve as carrier and targeting molecules, enabling and supporting HAV infection of IgA receptor-positive hepatocytes and, in the case of relapsing courses, allowing reinfection of the liver in the presence of otherwise neutralizing antibodies, resulting in exacerbation of liver disease.

Mx proteins in blood leukocytes for monitoring interferon beta-1b therapy in patients with MS.

OBJECTIVE: To correlate Mx protein (Mx) levels in lysed blood leukocytes with the clinical response to interferon (IFN) beta-1b (IFNbeta-1b) in relapsing-remitting MS (RR-MS) patients for monitoring treatment. BACKGROUND: Intracellular Mx expression is exclusively induced by the type I IFNs (IFN-alpha, -beta, and -omega) or by viruses and is strongly increased under IFN treatment. Quantitative determination of Mx allows objective assessment of biological effects of IFN. METHODS: Mx protein levels were measured in blood leukocyte lysates from IFNbeta-1b-treated RR-MS patients by ELISA and correlated to clinical parameters, including relapse rate and clinical deterioration. RESULTS: In stable IFNbeta-1b-treated MS patients, Mx levels were significantly increased compared to patients with or without immunosuppressive treatment. In IFN-1b-treated MS patients during relapse, Mx levels were significantly lower than during stable phases of the disease. Mean values of Mx (MVMx) over time of treatment in patients with a reduction of relapse rate were significantly higher than in patients without response. CONCLUSION: Mx levels in lysed blood cells may represent a useful surrogate marker for IFNbeta-1b activity corresponding to the clinical response during treatment of MS.

Expression of matrix metalloproteinase-9 and its inhibitors in mononuclear blood cells of patients with multiple sclerosis.

Inflammatory mononuclear cells invading the nervous system in demyelinating diseases are supposed to be a major source of matrix metalloproteinases which are involved in damaging the blood-brain barrier and facilitating cellular migration through the extracellular matrix. Several studies revealed a crucial role of 92 kDa gelatinase (matrix metalloproteinase-9, MMP-9) in these processes. In this study, we determined MMP-9, TIMP-1 and TIMP-2 (tissue inhibitor of metalloproteinase) mRNA in peripheral blood mononuclear cells of multiple sclerosis (MS) patients by competitive reverse transcription PCR and plasma protein levels by ELISA. In active MS patients, both with relapsing-remitting and chronic progressive disease MMP-9 mRNA and plasma protein levels were significantly increased compared to healthy controls. No significant changes in mRNA expression were found for TIMP-1 and TIMP-2. However, unbound TIMP-2 in plasma was significantly higher in MS patients compared to healthy controls. MMP-9 and TIMP-1 expression was significantly correlated in MS with a significantly higher MMP-9/TIMP-1 ratio in active MS than in healthy controls. These results are in support of an important pathogenic role of MMP-9 activity in MS.

Larynx-associated lymphoid tissue (LALT) in young children.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) plays a central role in mucosal immunity. Whereas the characteristics and function of MALT in the intestine are well established, almost nothing is known about MALT in the larynx. METHODS: In this study we examined the morphology and the lymphocyte subset composition of MALT in the larynges of children who had died of sudden infant death or various defined traumatic or nontraumatic causes. RESULTS: Organized lymphoid tissue was found in the supraglottic parts of the larynx in nearly 80% of the children in both groups. This lymphoid tissue showed all morphological signs of MALT, such as typical lymphoid follicles with germinal centers, infiltration of the overlying epithelium by lymphocytes, and high endothelial venules (HEV). Thus we will use the term LALT (larynx-associated lymphoid tissue) to refer to this tissue. The lymphoid follicles of LALT contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably, T lymphocytes of both subset types and B lymphocytes were observed in comparable numbers in the parafollicular area. CONCLUSIONS: We assume that LALT is a physiological structure of the larynx in young children. The morphology and the distribution of lymphocyte subsets are similar to those of MALT in the human gut. LALT may be a regular part of the mucosal immune system in young children with the role of respiratory inductive site for mucosal immunity.

Comparison of the immunohistology of mucosa-associated lymphoid tissue in the larynx and lungs in cases of sudden infant death and controls.

The respiratory tract of children in the first two years of life, unlike that of adults, contains bronchus-associated lymphoid tissue (BALT) and larynx-associated lymphoid tissue (LALT) with no differences in frequency between SID and control children. Using immunohistochemical methods we examined the distribution of B, T, CD4+ and CD8+ lymphocytes, HLA-D+ cells, CD68+ macrophages and proliferating cells, comparing bronchus-associated and larynx-associated lymphoid tissue of sudden infant death cases and controls. In all groups the lymphoid tissue was organized in lymphoid follicles and parafollicular areas. With no differences in the cellular composition of BALT and LALT the lymphoid follicles contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably T lymphocytes of both subset types and B lymphocytes were observed in equal numbers in the parafollicular areas in contrast to gut-associated lymphoid tissue. However, the respiratory tract of young children with no differences between SID and controls might play a similar role in mucosal immunity and might function as an inductive site.