UNTERSUCHUNG DER VERTEILUNG VERSCHIEDENER MIT LÖSUNGSMITTELFREIEN (ÄTHER FREIEN) KATALITISCHEN GRIGNARD-VERFAHREN HERGESTELLTEN PHENYLÄTHOXYSILANE

The distribution of the product mixtures from the one-step catalytic Grignard syntheses was investigated in the case of phenylethoxysilanes. It was stated, that the Fuoss distribution theory can be used for describing of the distribution of the differently substituted phenylethoxysilanes formed in the reaction-mixture only if the dependence of α and ß distribution coefficients on the R/Si (Phenyl-Silicon atom) ratio was taken into account during the reaction

Anti-salivary gland protein 1 antibodies in two patients with Sjogren’s syndrome: two case reports

INTRODUCTION: Current diagnostic criteria for Sjogren’s syndrome developed by the American College of Rheumatology include the presence of antinuclear antibodies, rheumatoid factor, anti-Ro or anti-La autoantibodies. The purpose of this report is to describe two patients with biopsy-proven Sjogren’s syndrome lacking these autoantibodies but identified by antibodies to salivary gland protein 1. Diagnosis was delayed until salivary gland tumors developed in these patients because of the lack of the classic autoantibodies. This report emphasizes the existence of patients with primary Sjogren’s syndrome who lack autoantibodies anti-Ro or anti-La and may therefore be misdiagnosed. Antibodies to salivary gland protein 1 identify some of these patients. CASE PRESENTATION: Two patients are described and were seen in the autoimmune disease clinics of the State University of New York (SUNY) at the Buffalo School of Medicine. In both patients, chronic dry mouth and dry eye had been dismissed as idiopathic because test results for autoantibodies anti-Ro and anti-La were negative. Both patients had swelling of major salivary glands that prompted biopsies. Biopsies of major salivary glands from both cases demonstrated salivary gland tumors and existence of inflammation consistent with Sjogren’s syndrome. Serologic testing revealed antibodies to salivary gland protein 1. CONCLUSIONS: Patients presenting with classic clinical symptoms of dry mouth and eyes do not always show the current serologic markers of Sjogren’s syndrome, anti-Ro and anti-La. In these cases, investigation for antibodies to salivary gland protein 1 is of importance to make the diagnosis of Sjogren’s syndrome. Early diagnosis of Sjogren’s syndrome is necessary for improved management as well as for vigilance regarding potential complications, such as salivary gland tumors as were seen in the described cases

Quantum superposition principle and gravitational collapse: Scattering times for spherical shells

A quantum theory of spherically symmetric thin shells of null dust and their gravitational field is studied. In Nucl. Phys. 603 (2001) 515 (hep-th/0007005), it has been shown how superpositions of quantum states with different geometries can lead to a solution of the singularity problem and black hole information paradox: the shells bounce and re-expand and the evolution is unitary. The corresponding scattering times will be defined in the present paper. To this aim, a spherical mirror of radius R_m is introduced. The classical formula for scattering times of the shell reflected from the mirror is extended to quantum theory. The scattering times and their spreads are calculated. They have a regular limit for R_m\to 0 and they reveal a resonance at E_m = c^4R_m/2G. Except for the resonance, they are roughly of the order of the time the light needs to cross the flat space distance between the observer and the mirror. Some ideas are discussed of how the construction of the quantum theory could be changed so that the scattering times become considerably longer.Comment: 30 pages and 5 figures; the post-referee version: shortened and some formulations improved; to be published in Physical Revie

Regulation of TRPC6 ion channels in podocytes — Implications for focal segmental glomerulosclerosis and acquired forms of proteinuric diseases

The glomerular filtration barrier is a highly specialized tri-layer structure with unique functional properties. Podocyte dysfunction and cytoskeletal disorganization leads to disruption of the slit diaphragma, and proteinuria. Inflammatory diseases involving the kidney as well as inherited podocytopathies or diabetic nephropathy cause injury of the podocyte network. Focal segmental glomerulosclerosis (FSGS) is a pathologic entity that is a common cause of nephrotic syndrome with severe proteinuria in both adults and children. Several causative genes have been identified in the pathogenesis of FSGS. Mutations of the transient receptor potential canonical-6 (TRPC6), a non-selective cation channel that is directly activated by diacylglycerol (DAG), cause a particularly aggressive form of FSGS. Angiotensin II, acting through its AT1 receptor, plays a critical role in generation of proteinuria and progression of kidney injury in a number of kidney diseases, including FSGS. Mounting evidence suggest the central role of TRPC6 and perhaps other TRPC channels in the pathogenesis of FSGS as well as of acquired forms of proteinuria such as diabetic nephropathy or hypertension. Identification of signaling pathways downstream of TRPC6 may provide novel targets for the treatment of proteinuria and prevent progression of podocyte injury

Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren's syndrome condition

Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells. Although the loss of salivary gland function is a major manifestation observed in pSS, the factors that could promote these changes in salivary gland tissue in pSS is not yet determined. Herein, we provide evidence that loss of alpha-1 antiproteinase antitrypsin could contribute to the induction of pSS. Alpha-1 antiproteinase antitrypsin belongs to the family of serpin proteins that function as protease inhibitors and protect secretory cells against proteases, especially to elastases that is secreted from lymphocytes. Importantly, expression of alpha-1 antiproteinase antitrypsin was decreased (more than 3-fold), along with an increase in elastase expression, in pSS samples when compared with age-matched non-SS-SICCA patients. Consistent with the human data, loss of alpha-1 antiproteinase antitrypsin, as well as an increase in immune infiltration, was observed in IL14α transgenic mice that exhibit SS like symptoms. Moreover, an age-dependent increase in elastase expression was observed in IL14α transgenic mice along with a decrease in total saliva secretion. Importantly, a 4-fold increase in microRNA132 expression, but not in other microRNAs, and increased DNA methylation in the promoter/noncoding region of serpina gene was observed in pSS, which could be responsible for the inhibition of alpha-1 antiproteinase antitrypsin expression in salivary gland cells of pSS patients. Together, these findings demonstrate that epigenetic regulations that include DNA methylation and microRNAs that could modulate the expression of alpha-1 antiproteinase antitrypsin in salivary glands and could be involved in the onset of pSS

The Bb fragment of complement factor B acts as a B cell growth factor.

The process of B cell growth and differentiation into plasma cells is highly regulated and may be influenced by a large number of inflammatory mediators, including complement components. We have studied the regulatory influence of Bb, a 60-kD peptide created during the cleavage of complement Factor B by Factor D and C3b. Purified Bb alone had no effect on proliferation and differentiation of human splenic or tonsillar B cells. However, when B cells were activated by Staphylococcus aureus Cowan I (SAC), Bb enhanced proliferation in a dose-dependent manner. Bb also enhanced proliferation when cocultured with SAC and suboptimal concentrations of purified 60-kD B cell growth factor (HMW-BCGF), a previously described lymphokine that is known to possess growth-promoting activity. However, Bb had no effect on cells treated with optimal concentrations of HMW-BCGF. Like HMW-BCGF, Bb's major effect was on the larger in vivo activated B cells. Half-maximal enhancement of proliferation was reached at a Bb concentration of 1-10 nM. Of note is the fact that antibody to Factor B recognized HMW-BCGF, and an mAb to HMW-BCGF also recognized Factor B and Bb, but not Ba. Moreover, radiolabeled Bb bound saturably to activated B cells and to an EBV-transformed human B cell line. The binding of Bb was inhibited by HMW-BCGF but not by Ba or IgG. Thus, Bb is antigenically and functionally related to HMW-BCGF, and can act as a B cell growth and differentiation factor at potentially physiologic concentrations. These data suggest that Bb may be important in amplifying the immune response in areas of inflammation. Since complement activation occurs at inflammatory sites long before induction of HMW-BCGF synthesis, Bb may be an early signal for the clonal expansion of antigen-activated B cells

Identification of a Small Molecule Inhibitor of Importin β Mediated Nuclear Import by Confocal On-Bead Screening of Tagged One-Bead One-Compound Libraries

In eukaryotic cells, proteins and RNAs are transported between the nucleus and the cytoplasm by nuclear import and export receptors. Over the past decade, small molecules that inhibit the nuclear export receptor CRM1 have been identified, most notably,leptomycin B. However, up to now no small molecule inhibitors of nuclear import have been described. Here we have used our automated confocal nanoscanning and bead picking method (CONA) for on-bead screening of a one-bead one-compound library to identify the first such import inhibitor, karyostatin 1A. Karyostatin 1A binds importin beta with high nanomolar affinity and specifically inhibits importin alpha/beta mediated nuclear import at low micromolar concentrations in vitro and in living cells, without perturbing transportin mediated nuclear import or CRM1 mediated nuclear export. Surface plasmon resonance binding-experiments suggest that karyostatin 1A acts by disrupting the interaction between importin p and the OPase Ran. As a selective inhibitor of the importin alpha/beta import pathway, karyostatin 1A will provide a valuable tool for future studies of nucleocytoplasmic trafficking.</p