Marguerite Mangin

Humoral Hypercalcemia of Cancer

THE syndrome of humoral hypercalcemia of cancer was first described by Fuller Albright in 1941.1 When a patients hypercalcemia and hypophosphatemia resolved after the radiation of a single bone me...

Clonal rat parathyroid cell line expresses a parathyroid hormone-related peptide but not parathyroid hormone itself

A novel parathyroid hormone-related peptide has been identified in tumors associated with the syndrome of humoral hypercalcemia of malignancy. Subsequently, mRNAs encoding this peptide have been found to be expressed in a number of normal tissues, including the parathyroids. Using Northern blotting, RNase protection, and immunochemical techniques, we examined a clonal rat parathyroid cell line originally developed as a model system for studying parathyroid cell physiology. We found that this line expresses the parathyroid hormone-related peptide but not parathyroid hormone itself. Secretion of the parathyroid hormone-related peptide varied inversely with extracellular calcium concentration, but neither calcium nor 1,25-dihydroxyvitamin D3 appeared to influence steady-state parathyroid hormone-related peptide mRNA levels. This clonal line may prove to be an interesting system for studying the factors responsible for tissue-specific parathyroid hormone and parathyroid hormone-related peptide gene expression.

The mitochondrial genomes of spontaneous orir petite mutants of yeast have rearranged repeat units organized as inverted tandem dimers.

We have investigated the structure and organization of the mitochondrial genomes of two related orir (ori-rearranged) spontaneous petite mutants of Saccharomyces cerevisiae. In these mutant genomes every repeat unit contains an inverted terminal duplication harboring a second (inverted) ori sequence, and tandem pairs of repeat units alternate with tandem pairs in inverted orientation. We have shown that orir genomes are organized as the genomes with inverted repeat units of ethidium bromide (EtBr)-induced petites, and we have clarified the mechanism by which such mutant mitochondrial genomes arise.

The orir to ori+ mutation in spontaneous yeast petites is accompanied by a drastic change in mitochondrial genome replication

The orir petite mutants of Saccharomyces cerevisiae show a very low level of suppressivity (5-12%; suppressivity is the percentage of diploid petites issued from a cross of the parental haploid petite with a wild-type cell), indicating a poor replication efficiency of their mitochondrial genome. The latter is made up of repeat units containing two inverted ori sequences and arranged as tandem pairs in inverted orientation relative to their nearest neighbors. After subcloning orir petites or crossing with wild-type cells a large number of ori+ petites are found in the progeny. In contrast to the orir petites, from which they are derived, these ori+ petites are characterized by high suppressivity levels (approx. 90%) and contain mitochondrial genomes made up of tandem repeat units containing single ori sequences. The structural changes underlying the orir to ori+ mutation are therefore accompanied by a dramatic increase in suppressivity, indicating that the elimination of inverted ori sequences causes a drastic change from very poor to very good replicative efficiency in the mitochondrial genome. Finally, crosses of ori0 petites with wild-type cells were also studied; the results obtained have clarified the reasons for the high frequency of petites having genomes similar to those of orir petites after mutagenesis with ethidium bromide.