Uppsala University

About: Uppsala University is a education organization based out in Uppsala, Sweden. It is known for research contribution in the topics: Population & Insulin. The organization has 36485 authors who have published 107509 publications receiving 4220668 citations. The organization is also known as: Uppsala universitet & uu.se.

Heterogeneity of Genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas.

Abstract: Six new permanent cell lines were established from human gliomas and compared to nine other cell lines from human gliomas. All fifteen lines had individually distinct HLA phenotypes and all but two, which were from a black patient, had type B glucose-6-phosphate-de;hydrogenase isoenzymes. Morphologically, the lines could be classified into four patterns descriptively designated as fibroblastic, fascicular, epithelial, or glial. Four of the lines grew progressively and could be serially transplanted when injected into athymic mice; two others grew initially and then regressed. From none to 100% of cells developed elongated tapering processes and showed reduction in nuclear-cytoplasmic ratio in the presence of 1 mM cyclic AMP and theophylline. Levels of 2'-3' cyclic nucleotide 3'-phosphohydrolase activity ranged from nondetectable to 12.78 +/- 1.49 micromoles 2' AMP formed per hr mgm total protein. None of the lines had detectable S-100 protein, but two had readily demonstrable glial fibrillary acidic protein in indirect immunofluorescence. Fibronectin levels in spent culture supernatants ranged from undetectable levels to 21.4 micrograms/ml/10(5) cells. All but one line shared surface antigens with normal human adult or fetal brain, as detected in absorption analyses with nonhuman primate antiserum raised against glioblastoma multiforme tissue or cell line U-251 MG. Although there were many common properties of the lines, each line had a unique profile of the parameters evaluated. This heterogeneity most likely reflects the individuality of the tumors of origin and individual genotypes and capacity for a range of phenotypic expression of cells.

Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism

Abstract: Adrenal aldosterone-producing adenomas (APAs) constitutively produce the salt-retaining hormone aldosterone and are a common cause of severe hypertension. Recurrent mutations in the potassium channel gene KCNJ5 that result in cell depolarization and Ca(2+) influx cause ∼40% of these tumors. We identified 5 somatic mutations (4 altering Gly403 and 1 altering Ile770) in CACNA1D, encoding a voltage-gated calcium channel, among 43 APAs without mutated KCNJ5. The altered residues lie in the S6 segments that line the channel pore. Both alterations result in channel activation at less depolarized potentials; Gly403 alterations also impair channel inactivation. These effects are inferred to cause increased Ca(2+) influx, which is a sufficient stimulus for aldosterone production and cell proliferation in adrenal glomerulosa. We also identified de novo germline mutations at identical positions in two children with a previously undescribed syndrome featuring primary aldosteronism and neuromuscular abnormalities. These findings implicate gain-of-function Ca(2+) channel mutations in APAs and primary aldosteronism.