[Joint swelling, reversible arm paresis, and elevated serum IgG4 in a 55-year-old man]. / Gelenkschwellungen, reversible Armparese und erhöhtes Serum-IgG4 bei einem 55-jährigen Patienten.

Only described in the last 10 years, IgG4-related disease is a fibroinflammatory disorder characterized by tumorous lesions with dense lymphoplasmacytic infiltration by IgG4-positive plasma cells and often elevated concentration of serum IgG4. In this paper, we present a male patient with this disease involving the lymph nodes and possibly the joints and kidneys. Infiltration of lymph node tissue with IgG4-positive plasma cells was demonstrated. The general condition of the patient improved considerably by immunosuppressive therapy.

Advanced glycation end products affect growth and function of osteoblasts.

OBJECTIVES: Advanced glycation end products (AGEs) have been implicated in the pathogenesis of bone-destructive disorders. Yet reports on the influence of AGEs on human osteoblasts remain lacking. The aim of the study is to investigate the influence of AGE-modified bovine serum albumin (AGE-BSA) on cell growth and expression of osteoblastic markers associated with osteogenesis and osteoclastogenesis. METHODS: Human osteoblasts established from bone tissue specimens were stimulated with AGE-BSA and investigated in vitro. Expression of mRNA for the receptor for AGEs (RAGE), nuclear factor kappa B subunit p65 (NFκB p65), tumour necrosis factor alpha (TNF-α), matrix metallo proteinase-1 (MMP-1), receptor activator of NFκB ligand (RANKL), osteoprotegerin, collagen type I (Col1), osteocalcin (OC) and alkaline phosphatase (ALP) were measured using real-time polymerase chain reaction (PCR). Respective protein expressions were evaluated by western blot analysis or ELISA. NFκB activation was investigated by luciferase assay and electrophoretic mobility shift assay (EMSA). Cell cycle analysis, cell proliferation and markers of necrosis and early apoptosis were assessed. RESULTS: AGE-BSA was actively taken up into osteoblasts and induced cell cycle arrest and an increase in necrotic, but not apoptotic cells. The increased expression of RAGE and TNF-α together with NFκB activation indicates an AGE-mediated inflammatory response. The decreased expression of Col1, OC and ALP presumably reflects a diminished osteogenic potential, whereas upregulation of RANKL and TNF-α enhances osteoclastogenesis. CONCLUSIONS: The present study demonstrates that AGE-BSA affects the growth and function of osteoblasts. Modulation of the expression of various target genes involved in bone metabolism provides evidence that AGEs accumulated in the bone matrix have the potential to suppress osteogenic and to promote osteoclastogenic properties of osteoblasts in vivo, thereby leading to functional and structural impairment of bone.

Decreased RAGE expression in peripheral blood mononuclear cells of patients with rheumatoid arthritis.

OBJECTIVE: Interactions between the multiligand receptor for advanced glycation end products (RAGE) and its proinflammatory ligands (AGEs, S100/calgranulins, HMBG1, Mac-1) may contribute to inflammatory responses playing a key role in the pathogenesis of chronic inflammatory diseases such as in rheumatoid arthritis (RA). Peripheral blood mononuclear cells (PBMCs) participate in the development of chronic inflammatory diseases. This study investigated expression of the RAGE variants endogenous secretory RAGE (esRAGE), N-truncated RAGE (NtRAGE) and complete RAGE (cRAGE: encoding full-length RAGE, esRAGE and NtRAGE) in PBMCs of patients with RA in comparison to healthy control subjects (controls) and to patients with Crohn's disease (CD) as another chronic inflammatory disease. METHODS: The cRAGE, esRAGE and NtRAGE mRNA expression levels of PBMCs from controls, RA and CD patients were measured by real-time PCR. The RAGE protein expression was determined by Western blot analysis and the esRAGE plasma levels by ELISA. RESULTS: PBMCs of RA patients showed significantly decreased mRNA expression for cRAGE (46%), esRAGE (54.0%) and NtRAGE (52%) in comparison to healthy controls (100%). For CD patients, also a down-regulation but to a lower extent was found (cRAGE: 79%; esRAGE: 76%; NtRAGE: 69%). Related to controls, RA PBMCs showed a significantly reduced protein expression of full-length RAGE (53%) as well as significantly decreased esRAGE plasma concentrations (70%). CONCLUSION: The down-regulation of RAGE isoforms in RA PBMCs may contribute to reduced intracellular responses mediated by the cell-standing receptor as well as to a lowered capability of trapping inflammatory ligands by circulating esRAGE.

Magnetization-switched metal-insulator transition in a (Ga,Mn)as tunnel device.

We observe the occurrence of an Efros-Shklovskii gap in (Ga,Mn)As based tunnel junctions. The occurrence of the gap is controlled by the extent of the hole wave function on the Mn acceptor atoms. Using k.p-type calculations we show that this extent depends crucially on the direction of the magnetization in the (Ga,Mn)As (which has two almost equivalent easy axes). This implies one can reversibly tune the system into the insulating or metallic state by changing the magnetization.

[Acute myopia and progressive acute renal failure in a 28-year old active horsewoman]. / Visusverlust und akutes Nierenversagen bei einer 28-jährigen aktiven Reiterin.

A 28-year old active sportswoman was admitted to hospital suffering from fever, menigeal irritation, acute myopia and progressive acute renal failure. Showing signs of polyserositis in combination with pulmonary granulomatous changes a collagenosis as well as an atypical pneumonia was excluded first. Due to the renal loss of function a renal biopsy was taken with the typical histological result of a hantavirus infection. This could be confirmed serologically in the following. With symptomatic treatment the patient had an uneventful complete recovery during the next four weeks.

Very large tunneling anisotropic magnetoresistance of a (Ga,Mn)As/GaAs/(Ga,Mn)As stack.

We report the discovery of a very large tunneling anisotropic magnetoresistance in an epitaxially grown (Ga,Mn)As/GaAs/(Ga,Mn)As structure. The key novel spintronics features of this effect are as follows: (i) both normal and inverted spin-valve-like signals; (ii) a large nonhysteretic magnetoresistance for magnetic fields perpendicular to the interfaces; (iii) magnetization orientations for extremal resistance are, in general, not aligned with the magnetic easy and hard axis; (iv) enormous amplification of the effect at low bias and temperatures.

Tunneling anisotropic magnetoresistance: a spin-valve-like tunnel magnetoresistance using a single magnetic layer.

We introduce a new class of spintronic devices in which a spin-valve-like effect results from strong spin-orbit coupling in a single ferromagnetic layer rather than from injection and detection of a spin-polarized current by two coupled ferromagnets. The effect is observed in a normal-metal-insulator-ferromagnetic-semiconductor tunneling device. This behavior is caused by the interplay of the anisotropic density of states in (Ga,Mn)As with respect to the magnetization direction and the two-step magnetization reversal process in this material.

Very large magnetoresistance in lateral ferromagnetic (Ga,Mn)as wires with nanoconstrictions.

We have fabricated (Ga,Mn)As nanostructures in which domain walls can be pinned by sub-10 nm constrictions. Controlled by shape anisotropy, we can switch the regions on either side of the constriction to either parallel or antiparallel magnetization. All samples exhibit a positive magnetoresistance, consistent with domain-wall trapping. For metallic samples, we find a magnetoresistance up to 8%, which can be understood from spin accumulation. In samples where, due to depletion at the constriction, a tunnel barrier is formed, we observe a magnetoresistance of up to 2000%.