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Biomedical subjects

J van der Sluys Veer

Publications and source records attributed to J van der Sluys Veer.

16 recordsLinked to original sources

Evolutionary pathways of the calcitonin (CALC) genes.

Recombinant DNA techniques have made it possible to establish the structure of various genes encoding polypeptide hormones. Comparison of nucleotide sequences of the calcitonin (CALC) genes in man has revealed surprising similarities and variations. These findings and the homologies among the sequences in different species offered an opportunity for speculation about relationships between these genes and about their evolutionary origin. The first gene (CALC-I) directing the synthesis of calcitonin (CT) or CT gene-related peptide (CGRP) comprises six exons and gives rise to two mRNAs by an alternative RNA-processing mechanism. The homology between CGRP and CT reflects their common origin. The human genome contains a second gene (CALC-II) that is structurally related to the CALC-I gene. The CALC-II RNA transcripts do not appear to be differentially processed, as only preproCGRP-II mRNA and not preproCT-II is detected. The first and second CT/CGRP genes probably have evolved from a common ancestor gene early in evolution. Meanwhile, a third genomic locus containing nucleotide sequences highly homologous to exons 2 and 3 of both CALC genes was detected and probably generated by duplication of a part of CALC-II. This locus is not likely to encode a CT- or CGRP-related polypeptide hormone. The CALC genes and this last (pseudo) gene are located on the short arm of chromosome 11. Recently, islet- or insulinoma-amyloid polypeptide (IAPP) was isolated as a major constituent of amyloid present in human insulinoma and in pancreatic islet amyloid in noninsulin-dependent diabetes mellitus. IAPP shows 46% amino acid sequence homology with human CGRP-II.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗

Evolutionary pathways of the calcitonin genes.

Since the development of molecular biology, knowledge about polypeptide hormones has increased rapidly. Recombinant DNA techniques have made it possible to establish the structure of genes encoding polypeptide hormones. The results have provided insight into the mechanisms underlying the increasing diversity of polypeptide hormones. Comparison of nucleotide sequences of various genes has revealed surprising similarities and variations. The calcitonin (CT) genes offered an opportunity for speculation about the evolutionary origin on one hand and relationships between these genes on the other.

Animals↗

Fluoride in serum and bone during treatment of osteoporosis with sodium fluoride, calcium and vitamin D.

Thirteen patients with primary osteoporosis were treated for two years with sodium fluoride (NaF), calcium and dihydrotachysterol (group A). The dose of NaF was modified according to the serum fluoride concentration, which was kept as constant as possible between 0.20 and 0.25 microgram/ml. In patients with bone fluoride content greater than or equal to 0.20% a significant increase in the volumetric density and in the surface percentage covered with osteoid and with osteoblasts was observed. A second group of 7 patients with primary osteoporosis was also treated for 2 years with calcium and dihydrotachysterol, but without fluoride (group B). In these patients no significant change in the volumetric density or in the surface percentage covered with osteoid or osteoblasts was found. Patients in group A with a bone fluoride content less than 0.20% could not be distinguished from the patients in group B. Based on the available data an advice was given for the dosage of NaF in patients with osteoporosis. Regular assessment of the serum fluoride concentration remains advisable.

Adult↗

The use of hydroxy-DL-proline-2-(14)C in the investigation of hydroxyproline metabolism in normal subjects and in patients with renal insufficiency.

The metabolism of hydroxyproline was investigated in six healthy subjects and four patients with chronic renal insufficiency (creatinine clearances respectively 40, 10, 7, 2 1/2 ml/min). For this purpose hydroxy-DL-proline-2-(14)C was administered intravenously and the excretion patterns of radio-activity in plasma, urine and expired air (14CO2) were determined. A separation procedure (using thin layer chromatography followed by oxidation with D-amino acid oxidase) made it possible to determine the concentration of hydroxy-L-proline-2-(14)C in the presence of the D-isomer and the degradation products of both. Although the use of a racemic mixture as tracer made conclusions more difficult, it could be shown that in uremic patients the concentration of hydroxy-DL-proline -2-(14)C remained high in the blood for a longer period, the metabolites appeared in the urine later, and the peak respiratory 14CO2 excretion was reached later and was lower than in the healthy subjects. On this basis it was concluded that the metabolism of hydroxyproline is diminished in patients with renal insufficiency.

Adult↗