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Biomedical subjects

O Maier

Publications and source records attributed to O Maier.

10 recordsLinked to original sources

Fundic gland polyps (Elster's cysts) of the gastric mucosa. A marker for colorectal epithelial neoplasia?

The results of several retrospective studies allow us to conclude that the detection of fundic gland polyps (Elster's cysts) is associated with an increased incidence of colorectal tumors. In this survey, we present the results of a prospective study investigating such a possible relationship. A total of 144 patients were investigated, of whom 80 had fundic gland polyps of the gastric corpus mucosa. Sixty-four of these patients underwent a colonoscopy, whereas the other 64 patients belonged to a sex- and age-matched control group with no fundic gland polyps. In the group with known fundic gland polyps, colorectal neoplasias were found in 29 (45.3%) patients. Eight of these patients had (12.5%) adenocarcinomas, 3 (4.7%) had high-grade intraepithelial neoplasia, and 18 (28.1%) had tubular adenomas. In one patient, a synchronous carcinoma of the rectum and the colon was detected. In comparison, 6 patients of the control group (9.3%) developed tubular adenomas and 9 (14.1%) had hyperplastic polyps of the colonic and rectal mucosa. Our results suggest that it is necessary to conduct a careful diagnostic work-up of the colon in patients with gastric fundic gland polyps.

Biomarkers, Tumor↗

Membrane domains and polarized trafficking of sphingolipids.

The plasma membrane of polarized cells consists of distinct domains, the apical and basolateral membrane, that are characterized by a distinct lipid and protein content. Apical protein transport is largely mediated by (glyco)sphingolipid--cholesterol enriched membrane microdomains, so called rafts. In addition changes in the direction of polarized sphingolipid transport appear instrumental in cell polarity development. Knowledge is therefore required of the mechanisms that mediate sphingolipid sorting and the complexity of the trafficking pathways that are involved in polarized transport of both sphingolipids and proteins. Here we summarize specific biophysical properties that underly mechanisms relevant to sphingolipid sorting, cargo recruitment and polarized trafficking, and discuss the central role of a subapical compartment, SAC or common endosome (CE), as a major intracellular site involved in polarized sorting of sphingolipids, and in development and maintenance of membrane polarity.

Animals↗

The subapical compartment and its role in intracellular trafficking and cell polarity.

In polarized epithelial cells and hepatocytes, apical and basolateral plasma membrane surfaces are maintained, each displaying a distinct molecular composition. In recent years, it has become apparent that a subapical compartment, referred to as SAC, plays a prominent if not crucial role in the domain-specific sorting and targeting of proteins and lipids that are in dynamic transit between these plasma membrane domains. Although the molecular identity of the traffic-regulating devices is still obscure, the organization of SAC in distinct subcompartments and/or subdomains may well be instrumental to such functions. In this review, we will focus on the potential subcompartmentalization of the SAC in terms of regulation of membrane traffic, on how SAC relates to the endosomal system, and on how this compartment may operate in the context of other intracellular sorting organelles such as the Golgi complex, in generating and maintaining cell polarity.

Animals↗

On the mechanism of intracellular membrane fusion: in search of the genuine fusion factor.

Intracellular membrane fusion events require a general protein machinery that functions in vesicular traffic and in assembly and maintenance of organelles. An array of cytosolic and integral membrane proteins are currently identified, and in conjunction with ongoing detailed structural studies, rapid progress is made in understanding basic features of the overall mechanism of the fusion machinery, but above all a proper appreciation of its enormous complexity. Thus a highly sophisticated level of regulation of the different steps involved in tethering, docking and merging itself is apparent. Apart from the relevance of protein-protein interactions, also a role of distinct lipids is gradually emerging, particularly in fusion. However, although various suggestions have been made recently, largely based upon in vitro studies, the identity of the actual fusion factor(s) remains to be determined.

Carrier Proteins↗

Protein kinase C bound to the Golgi apparatus supports the formation of constitutive transport vesicles.

Constitutive secretion of heparan sulphate proteoglycans (HSPGs) was stimulated in human hepatoma HepG2 cells by phorbol 12-myristate 13-acetate (PMA) and inhibited by calphostin C, a specific inhibitor of protein kinase C (PKC). To delineate more closely the site of PKC action, the packaging in vitro of 35SO4-labelled HSPGs into transport vesicles was investigated. Formation of transport vesicles at the trans-Golgi network was stimulated by PMA and inhibited by calphostin C or Ro 31-8220 by using a post-nuclear supernatant. Treatment of either isolated Golgi-enriched membranes or cytosolic proteins with calphostin C provided evidence that membrane-bound PKC forms strongly supported vesicle formation, whereas cytosolic PKC forms showed a marginal effect. The PKC isoforms PKC-alpha and PKC-zeta were attached to highly purified Golgi membranes, as shown by Western blotting. Both isoforms were localized by confocal immunofluorescence microscopy in the Golgi area of HepG2 cells. Immunoelectron microscopy of ultrathin cryosections of HepG2 cells showed that PKC-zeta predominantly attaches to the trans-Golgi region, whereas PKC-alpha binds to the cis- and trans-Golgi area.

Carcinoma, Hepatocellular↗

Dynamin II binds to the trans-Golgi network.

Two dynamin II-specific antibodies were used to detect dynamin II attached to highly purified Golgi membranes of HepG2 cells. Within the Golgi apparatus dynamin II is predominantly localized to the trans-Golgi network, as shown by immunoelectron microscopy. Increased binding of dynamin II to the trans-Golgi network in the presence of GTP-gamma-S and a reduced binding upon stimulation of secretion by phorbolester indicates that dynamin II may have a function in post-Golgi vesicle transport.

Amino Acid Sequence↗

Trimeric G protein alpha subunits of the Gs and Gi families localized at the Golgi membrane.

The occurrence of individual G proteins within Golgi membranes from liver and from adrenal medulla were analyzed by Western blotting. Two splice variants of G alpha s and also G alpha i-3 were found in both tissues. Additionally, G alpha i-2, its 43-kDa splice variant and G alpha o were strongly labeled in Golgi of adrenal medulla. Golgi preparations of liver contained comparable quantities of G alpha i-2 and a second variant of 46 kDa, but no G alpha o was detected. Immunoelectron microscopic studies of the above Golgi preparations showed that both G alpha i-2 and G alpha i-3 are localized at multivesicular structures identified as Golgi complexes. The occurrence of two stimulatory G proteins (G alpha s-S and G alpha s-L) and three or four alpha subunits of the Gi/Go type as components of the Golgi membrane support the notion that formation of different vesicle types might be regulated by individual stimulatory and inhibitory G proteins.

Adrenal Medulla↗

Prevalence of antibodies against HEp-2 cell antigen in infants and children hospitalized with respiratory syncytial virus infection.

Infants with respiratory syncytial virus (RSV) infection were shown to have antibodies against HEp-2 cell antigen present in RSV-antigen preparation used for immunoblot analysis. The prevalence of anti HEp-2 cell antibodies was examined in infants hospitalized for RSV infection (n = 49, median age 121 days) compared to rotavirus infected children (n = 30, median age 114 days) and to healthy controls (n = 20, median age 150 days). The immunoblot analysis with RSV-infected and non-infected HEp-2 cells as antigen revealed the expected age-dependent low prevalence of G protein antibodies and clear seroconversion of N and P protein antibodies. HEp-2 antibody prevalence was higher in RSV antigen-positive infants (33/49) than in rotavirus antigen-positive (5/30) and RSV antigen-negative infants (4/20), respectively (p < 0.001). Anti HEp-2 antibodies were mostly directed against 47, 46, 33, 30 kD antigens. A multiple regression analysis found the following correlations (odds ratio; 95% confidence interval): 42 kD RSV antibodies (N protein) with pneumonia (7.58; 1.43-40), 94 kD RSV antibodies (G protein) with bronchiolitis (0.064; 0.006-0.686). This study shows repeated well-known features of humoral immunity in RSV infection. The data on anti HEp-2 antibodies point to a role for these pre-existing autoreactive antibodies in the pathogenesis of RSV infection.

Acute Disease↗