University of Graz

About: University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Context (language use). The organization has 17934 authors who have published 37489 publications receiving 1110980 citations. The organization is also known as: Carolo Franciscea Graecensis & Karl Franzens Universität.

The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats

Abstract: PTH treatment can result in dramatic increases in cancellous bone volume in normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of PTH leads to hypercalcemia and bone abnormalities. The purpose of these studies was to determine the optimal duration of the PTH pulses. A preliminary study revealed that human PTH-(1-34) (hPTH) is cleared from circulation within 6 h after sc administration of an anabolic dose of the hormone (80 microg/kg). To establish the effects of gradually extending the duration of exposure to hPTH without increasing the daily dose, we programmed implanted Alzet osmotic pumps to deliver the 80 microg/kg x day dose of the hormone during pulses of 1, 2, and 6 h/day, or 40 microg/kg x day continuously. Discontinuous infusion was accomplished by alternate spacing of external tubing with hPTH solution and sesame oil. After 6 days of treatment, we evaluated serum chemistry and bone histomorphometry. As negative and positive controls, groups of rats received pumps that delivered vehicle only and 80 microg/kg x day hPTH by daily sc injection, respectively. Dynamic and static bone histomorphometry revealed that the daily sc injection and 1 h/day infusion dramatically increased osteoblast number and bone formation in the proximal tibial metaphysis, whereas longer infusion resulted in systemic side-effects, including up to a 10% loss in body weight, hypercalcemia, and histological changes in the proximal tibia resembling abnormalities observed in patients with chronic primary hyperparathyroidism, including peritrabecular marrow fibrosis and focal bone resorption. Infusion for as little as 2 h/day resulted in minor weight loss and changes in bone histology that were intermediate between sc and continuous administration. The results demonstrate that the therapeutic interval for hPTH exposure is brief, but that programmed administration of implanted hormone is a feasible alternative to daily injection as a route for administration of the hormone.

The morphologic correlate of incidental punctate white matter hyperintensities on MR images.

Abstract: Postmortem examinations were made of the brains of six patients, 52-63 years old, who exhibited incidental punctate white matter hyperintensities on MR images before death. Our aim was to unravel the morphologic correlate of such lesions. By repeating the MR study after fixation on four specimens, cutting the brain parallel to the MR imaging plane, and examining whole-hemisphere microscopic sections, we optimized lesion identification. The white matter signal abnormalities were better delineated on pre- than postmortem scans, and visual inspection of the brain slices was normal in all but one location. Histologically, we found areas of reduced myelination with atrophy of the neuropil around fibrohyalinotic arteries as well as different stages of perivenous damage. The latter ranged from spongiform transformation of the neuropil and scattered foci of demyelination to large perivenous areas with marked rarefaction of myelinated fibers. Edematous glial swelling in foci of ganglion cell heterotopia caused subcortical white matter hyperintensities in one case. Our results suggest minor perivascular damage but not infarction as the most likely substrate of punctate MR white matter hyperintensities in elderly brains. Histologic correlations with MR images obtained during life or with studies of unfixed material are necessary to analyze such small lesions.

Association between the endoplasmic reticulum and mitochondria of yeast facilitates interorganelle transport of phospholipids through membrane contact.

Abstract: Membrane association between mitochondria and the endoplasmic reticulum of the yeast Saccharomyces cerevisiae is probably a prerequisite for phospholipid translocation between these two organelles. This association was visualized by fluorescence microscopy and computer-aided three-dimensional reconstruction of electron micrographs from serial ultrathin sections of yeast cells. A mitochondria-associated membrane (MAM), which is a subfraction of the endoplasmic reticulum, was isolated and re-associated with mitochondria in vitro. In the reconstituted system, phosphatidylserine synthesized in MAM was imported into mitochondria independently of cytosolic factors, bivalent cations, ATP, and ongoing synthesis of phosphatidylserine. Proteolysis of mitochondrial surface proteins by treatment with proteinase K reduced the capacity to import phosphatidylserine. Phosphatidylethanolamine formed in mitochondria by decarboxylation of phosphatidylserine is exported to the endoplasmic reticulum where part of it is converted into phosphatidylcholine. In contrast with previous observations with permeabilized yeast cells [Achleitner, G., Zweytick, D., Trotter, P., Voelker, D. & Daum, G. (1995) J. Biol. Chem.270, 29836–29842], export of phosphatidylethanolamine from mitochondria to the endoplasmic reticulum was shown to be energy-independent in the reconstituted yeast system.