Biomedical subjects

C Grewe

Publications and source records attributed to C Grewe.

5 recordsLinked to original sources

PubMed2001

Alterations at the Ink4a locus in transplacentally induced murine lung tumors.

The malignant phenotype results from multiple genetic alterations, including the activation of oncogenes and inactivation of tumor suppressor genes. Activation of the Ki-ras oncogene has been implicated as an early event in the pathogenesis of lung adenocarcinomas in humans and experimental animal models. Previous studies from this laboratory have shown that, following treatment of pregnant [D2 x B6D2F(1)]F(2) or Balb/c mice with the polycyclic aromatic hydrocarbon, 3-methylcholanthrene (MC), lung tumors from the transplacentally exposed offspring exhibited a high incidence of mutations in the Ki-ras gene. The role of genetic alterations at other oncogenic or tumor suppressor loci that can mediate lung tumor initiation and/or progression have not been well characterized in either human or murine models. Using the transplacental carcinogenesis model, which results in the induction of both lung and liver tumors following in utero exposure to MC, the results of this and our previous studies show that alterations in the Ink4a locus occur in only 15 and 27% of the lung and liver tumors, respectively. Preliminary data also suggests that the type of mutation induced in the Ki-ras gene following the initial exposure to MC may influence lung tumor progression. These results imply that damage to the Ink4a gene is not a frequent pathway to malignant progression in mouse lung and liver tumors following in utero exposure to environmental carcinogens.

Animals↗

PubMed1996

Immunolocalization of a 22 kDa protein (IPLA7, P22) of Borrelia burgdorferi.

The monoclonal antibody LA7 was raised against the species-specific Borrelia burgdorferi lipoprotein P22 (= IPLA7), which induces antibody formation in patients with Lyme arthritis. It is composed of 194 amino acids with a calculated molecular mass of 21.8 kDa. Its gene on the linear chromosome is 582 nucleotides in length. The aim of this study was to localize the protein P22 by immune electron microscopy. Immunolabeling of Borrelia burgdorferi with LA7 and an anti-mouse immunogold conjugate proved that P22 is an outer membrane protein. This finding was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis of the outer envelope fraction, which contained 99% of the P22 proteins.

Animals↗

PubMed1990

HIV: early virus-cell interactions.

Two entry mechanisms of HIV occur in both lymphocytes and macrophages incubated with purified virus suspensions: (a) direct fusion of the viral envelope with the cell membrane and (b) receptor-mediated endocytosis via clathrin-coated pits and vesicles. Both mechanisms are shown in detail in a time-interval series of electron micrographs. The two lipid bilayers of the viral envelope and of the cellular membrane usually fuse seamlessly within 1-3 min at 37 degrees C, but occasionally membrane ruptures occur, leading to rapid cytopathic effects, i.e., vacuolization and cytolysis only a few minutes later. In the course of virus-cell fusion, gp 120 is integrated into the cell membrane; subsequent syncytia formation was observed after 1 h of incubation. The core disintegrates and releases the viral ribonucleoprotein through the opening at the fusion site into the cytoplasm.

Adsorption↗

PubMed1986

Receptor-mediated actions of corticotropin-releasing factor in pituitary gland and nervous system.

High-affinity corticotropin-releasing factor (CRF) receptors which mediate the actions of the hypothalamic peptide on adrenocorticotropic hormone (ACTH) release have been identified in the rat anterior pituitary gland. Occupancy of the pituitary receptor by CRF agonists stimulates ACTH release via activation of adenylate cyclase and cyclic adenosine monophosphate dependent protein kinase. In the regulation of ACTH secretion, the effects of CRF on the corticotroph are integrated with the stimulatory actions of cyclic adenosine monophosphate-independent stimuli such as angiotensin II, vasopressin and norepinephrine, and the inhibitory effects of glucocorticoids and somatostatin. In contrast to the major importance of the inhibitory effect of glucocorticoid feedback on ACTH secretion, somatostatin has relatively little effect on CRF-stimulated ACTH release in the normal rat corticotroph. Following adrenalectomy, the progressive elevation of plasma ACTH levels is accompanied by a concomitant decrease in pituitary CRF receptors. The postadrenalectomy loss of CRF receptors, which is prevented by dexamethasone treatment, is caused by a combination of occupancy and processing of the pituitary sites during increased secretion of the hypothalamic peptide. Recently, specific receptors for CRF have been localized in the rat and monkey brain and adrenal medulla, where they are also coupled to adenylate cyclase. Brain CRF receptors are most abundant in the cerebral and cerebellar cortices and in structures related to the limbic system and control of the autonomic nervous system. The actions of CRF on the central and peripheral nervous systems, as well as on the pituitary gland, emphasize the role of CRF as a key hormone in the integrated response to stress.

Adrenocorticotropic Hormone↗

PubMed1984

Actions of growth hormone-releasing factor and somatostatin on adenylate cyclase and growth hormone release in rat anterior pituitary.

The interaction of growth hormone-releasing factor (GRF) and somatostatin (SRIF) on adenylate cyclase activity and growth hormone release was investigated in pituitary homogenates and 2-day cultured rat anterior pituitary cells. GRF stimulated growth hormone release by about 3-fold (ED50 1.6 X 10(-12) M) and caused a rapid 15-fold increase in cyclic AMP production (ED50 6.0 X 10(-12) M). The increase in cyclic AMP was due to direct stimulation of adenylate cyclase by GRF, which caused a 4-fold increase in the activity of the enzyme measured in anterior pituitary homogenates. GRF-induced cyclic AMP formation and GRF-stimulated adenylate cyclase activity were maximally inhibited to the extent of about 50% by 10(-8) M somatostatin. In contrast, GRF-stimulated growth hormone release was completely inhibited by somatostatin (ID50 3.2 X 10(-11) M), suggesting a second site of action of somatostatin. These studies demonstrate that GRF stimulates growth hormone release via activation of adenylate cyclase and a rise in intracellular cyclic AMP. In addition, these findings indicate that the inhibitory action of somatostatin on growth hormone release is exerted at two levels, one at the level of adenylate cyclase affecting the production of cyclic AMP, and the other beyond the formation of the nucleotide, at a site which modulates the release of growth hormone from the cell.

Adenylyl Cyclases↗