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Biomedical subjects

W Gartner

Publications and source records attributed to W Gartner.

7 recordsLinked to original sources
PubMed2001

Cerebral expression and serum detectability of secretagogin, a recently cloned EF-hand Ca(2+)-binding protein.

Recently we identified a novel EF-hand Ca-binding protein termed secretagogin, which is expressed in neuroendocrine cells. Immunohistochemical investigations, using a murine monoclonal and an affinity purified rabbit polyclonal anti-secretagogin antibody as well as Northern-blot and Western-blot analysis revealed a neuron-specific cerebral expression pattern. Secretagogin was detected in high quantity in basket and stellate cells of the cerebellar cortex, in secretory neurons of the anterior part of the pituitary gland and in singular neurons of the frontal and parietal neocortex. Remarkable staining intensity was observed in hypothalamic and in hippocampal neurons. Using a newly developed sandwich capture ELISA we show presence of secretagogin in serum of patients suffering from hypoxic neuronal damage. In sera obtained from 32 patients with different forms of neurological symptoms due to focal cerebral ischemia, secretagogin levels ranged from 3 to 236 pg/ml, with highest levels observed on days 2 and 3 after infarction. Three patients exhibiting minor, reversible neurological deficits had nondetectable serum secretagogin levels at time points of testing. In 50 control sera, secretagogin was below the detection limit of our ELISA. Parallel analysis of secretagogin and the established neurobiochemical marker S-100B in 14 representative patients revealed comparable results. However, S-100B levels were higher and exhibited different kinetics than secretagogin. Our data present the cerebral expression pattern of secretagogin and give evidence that this protein might represent a clinically relevant serum marker indicative for neuronal damage.

Adult↗
PubMed2000

Cloning and expression of secretagogin, a novel neuroendocrine- and pancreatic islet of Langerhans-specific Ca2+-binding protein.

We have cloned a novel pancreatic beta cell and neuroendocrine cell-specific calcium-binding protein termed secretagogin. The cDNA obtained by immunoscreening a human pancreatic cDNA library using the recently described murine monoclonal antibody D24 contains an open reading frame of 828 base pairs. This codes for a cytoplasmic protein with six putative EF finger hand calcium-binding motifs. The gene could be localized to chromosome 6 by alignment with GenBank genomic sequence data. Northern blot analysis demonstrated abundant expression of this protein in the pancreas and to a lesser extent in the thyroid, adrenal medulla, and cortex. In addition it was expressed in scant quantity in the gastrointestinal tract (stomach, small intestine, and colon). Thyroid tissue expression of secretagogin was restricted to C-cells. Using a sandwich capture enzyme-linked immunosorbent assay with a detection limit of 6.5 pg/ml, considerable amounts of constitutively secreted protein could be measured in tissue culture supernatants of stably transfected RIN-5F and dog insulinoma (INS-H1) cell clones; however, in stably transfected Jurkat cells, the protein was only secreted upon CD3 stimulation. Functional analysis of transfected cell lines expressing secretagogin revealed an influence on calcium flux and cell proliferation. In RIN-5F cells, the antiproliferative effect is possibly due to secretagogin-triggered down-regulation of substance P transcription.

Amino Acid Sequence↗
PubMed2000

Signaling states of rhodopsin. Retinal provides a scaffold for activating proton transfer switches.

The G-protein-coupled receptor rhodopsin is activated by photoconversion of its covalently bound ligand 11-cis-retinal to the agonist all-trans-retinal. After light-induced isomerization and early photointermediates, the receptor reaches a G-protein-dependent equilibrium between active and inactive conformations distinguished by the protonation of key opsin residues. In this report, we study the role of the 9-methyl group of retinal, one of the crucial steric determinants of light activation. We find that when this group is removed, the protonation equilibrium is strongly shifted to the inactive conformation. The residually formed active species is very similar to the active form of normal rhodopsin, metarhodopsin II. It has a deprotonated Schiff base, binds to the retinal G-protein transducin, and is favored at acidic pH. Our data show that the normal proton transfer reactions are inhibited in 9-demethyl rhodopsin but are still mandatory for receptor activation. We propose that retinal and its 9-methyl group act as a scaffold for opsin to adjust key proton donor and acceptor side chains for the proton transfer reactions that stabilize the active conformation. The mechanism may also be applicable to related receptors and may thus explain the partial agonism of certain ligands.

Animals↗
PubMed1999

Multi-component apparent diffusion coefficients in human brain.

The signal decay with increasing b-factor at fixed echo time from brain tissue in vivo has been measured using a line scan Stejskal-Tanner spin echo diffusion approach in eight healthy adult volunteers. The use of a 175 ms echo time and maximum gradient strengths of 10 mT/m allowed 64 b-factors to be sampled, ranging from 5 to 6000 s/ mm2, a maximum some three times larger than that typically used for diffusion imaging. The signal decay with b-factor over this extended range showed a decidedly non-exponential behavior well-suited to biexponential modeling. Statistical analyses of the fitted biexponential parameters from over 125 brain voxels (15 x 15 x 1 mm3 volume) per volunteer yielded a mean volume fraction of 0.74 which decayed with a typical apparent diffusion coefficient around 1.4 microm2/ms. The remaining fraction had an apparent diffusion coefficient of approximately 0.25 microm2/ms. Simple models which might explain the non-exponential behavior, such as intra- and extracellular water compartmentation with slow exchange, appear inadequate for a complete description. For typical diffusion imaging with b-factors below 2000 s/mm2, the standard model of monoexponential signal decay with b-factor, apparent diffusion coefficient values around 0.7 microm2/ms, and a sensitivity to diffusion gradient direction may appear appropriate. Over a more extended but readily accessible b-factor range, however, the complexity of brain signal decay with b-factor increases, offering a greater parametrization of the water diffusion process for tissue characterization.

Adult↗
PubMed1996

Conversion of energy in halobacteria: ATP synthesis and phototaxis

Halobacteria are aerobic chemo-organotroph archaea that grow optimally between pH 8 and 9 using a wide range of carbon sources. These archaea have developed alternative processes of energy provision for conditions of high cell densities and the reduced solubility of molecular oxygen in concentrated brines. The halobacteria can switch to anaerobic metabolism by using an alternative final acceptor in the respiratory chain or by fermentation, or alternatively, they can employ photophosphorylation. Light energy is converted by several retinal-containing membrane proteins that, in addition to generating a proton gradient across the cell membrane, also make phototaxis possible in order to approach optimal light conditions. The structural and functional features of ATP synthesis in archaea are discussed, and similarities to F-ATPases (functional aspects) or vacuolar ATPases (structural aspects) are presented.

Journal Article↗
PubMed1976

Conversion of a benign lymphoepithelial salivary gland lesion to lymphocytic lymphoma during dilantin therapy: correlation with dilantin-induced lymphocyte transformation in vitro.

A patient with a classical salivary gland benign lymphoepithelial lesion (BLL) that converted to a lymphoblastic lymphoma (LSA) localized to the salivary glands is described. The malignant transformation of the BLL was preceded by Dilantin anticonvulsant therapy, and in vitro tests subsequent to the development of LSA demonstrated positive Dilantin-induced lymphocyte transformation. The lymphoma was treated successfully by local irradiation, chemotherapy, and discontinuation of Dilantin. The case illustrates the "prelymphomatous" nature of BLL in certain patients, as well as the possible potential danger of Dilantin and other lymphoid-stimulating drugs in discussed. Further study of drugs capable lymphocyte transformation in patients with prelymphomatous disorders is warranted.

Cell Transformation, Neoplastic↗