Aspects of Parathyroid Physiology in Mammals

This report summarizes the parameters of parathyroid physiologyin the mammal. Emphasis is given to the part played by thishormone in the processes of growth and remodelling in bone aswell as to its function in the maintenance of a relatively constantlevel of ionic calcium in the extracellular fluid. The importanceof phosphate ions has been shown, particularly with respectto their role in the rate of Ca-transport through the extracellularfluid compartments, and their influence on the rate of parathyroidsecretion. In addition, the inter-relationship of the newlydiscovered hormone, thyrocalcitonin, is considered. The latterhormone, by suppressing resorption of bone, may have an influencein stabilizing plasma levels of calcium; it also has a moderate,but long range effect on the rate of bone remodelling. Finally,an attempt has been made to relate the vast amount of work donewith these two hormones in mammals to their phylogenetic developmentin vertebrates. It is suggested that the parathyroids developedat the time when the specialization of bone in vertebrates produceda solid structure which was incompatible with the fluid calciumconcentration needed for the maintenance of many physiologicalfunctions. The parathyroid hormone, by its action to increasethe transfer of calcium from bone against a concentration gradient,permitted these vertebrates to maintain the higher fluid calciumion concentration needed for the normal functioning of the animal.     

Mortality in Spinal Cord Injuries—Follow-up Report

The principal cause among 137 deaths in a series of 1,613 patients with traumatic spinal cord lesions treated at Veterans Administration Hospital, Long Beach, was renal disease attributable to the paralysis of the bladder and bladder sphincter and resultant genito-urinary tract infections. The second ranking cause was pulmonary disease. Before 1960 no deaths from cancer had occurred in this series, but between 1960 and 1962 three patients died of carcinoma of the bladder. It can be expected that as these patients reach higher age groups the incidence of neoplasms will increase.     

Regulation of fibrinogen assembly. Transfection of Hep G2 cells with B beta cDNA specifically enhances synthesis of the three component chains of fibrinogen

Previous studies indicated that synthesis of B beta chain may be a rate-limiting factor in the production of human fibrinogen since Hep G2 cells contain surplus pools of A alpha and gamma but not of B beta chains, and fibrinogen assembly commences by the addition of preformed A alpha and gamma chains to nascent B beta chains attached to polysomes. To test whether B beta chain synthesis is rate limiting Hep G2 cells were transfected with B beta cDNA, and its effect on fibrinogen synthesis and secretion was measured. Two sets of stable B beta cDNA-transfected Hep G2 cells were prepared, and both cell lines synthesized 3-fold more B beta chains than control cells. The B beta-transfected cells also synthesized and secreted increased amounts of fibrinogen. Transfection with B beta cDNA not only increased the synthesis of B beta chain but also increased the rate of synthesis of the other two component chains of fibrinogen and maintained surplus intracellular pools of A alpha and gamma chains. Transfection with B beta cDNA did not affect the synthesis of albumin, transferrin, or anti-chymotrypsin and had a small inhibitory effect on the synthesis of C-reactive protein. Taken together these studies demonstrate that increased B beta chain synthesis specifically causes increased production of the other two component chains of fibrinogen and that unequal and surplus amounts of A alpha and gamma chains are maintained intracellularly.     

Involvement of calcium, calmodulin and protein phosphorylation in morphogenesis of Candida albicans

N-Acetyl-D-glucosamine-induced germ tube formation in Candida albicans at 37 degrees C was accompanied by an increase in the rate of protein phosphorylation. The calmodulin antagonist trifluoperazine and the Ca2+ ionophore A23187, which inhibited germ tube formation, also reduced the rate of phosphorylation. The rate of phosphorylation was also reduced when cells were incubated at 25 degrees C, which favoured yeast-phase growth. Two-dimensional SDS-PAGE analysis of phosphoproteins from germ-tube-forming and yeast cells revealed two germ-tube-specific and three yeast-specific phosphoproteins. Germ tubes and hyphae had more calmodulin activity than yeast cells, irrespective of the germ-tube-inducing condition used. As a first step towards understanding the inhibitory effect of trifluoperazine on germ tube formation, calmodulin from C. albicans was purified to homogeneity. It was heat stable, and displayed a pronounced Ca2(+)-induced shift in electrophoretic mobility.     

Structure of testicular angiotensin-converting enzyme. A segmental mosaic isozyme

The complete amino acid sequence of rabbit testicular angiotensin-converting enzyme has been deduced from the sequence of the corresponding cDNA clone. A protein of the expected molecular weight of 84,000 was translated in vitro from the mRNA encoded by this cDNA. All of the previously determined sequences of seven tryptic peptides from the enzyme are present in the deduced sequence, thus confirming the identity of the protein. From the deduced sequence it appears that the protein contains a signal peptide at the amino terminus and a hydrophobic anchoring domain near the carboxyl terminus. Northern analysis with oligonucleotide probes, whose sequences represented different regions of the cDNA, revealed not only the regions of extensive homology between the mRNAs encoding the testicular and the pulmonary isozymes but also a stretch of sequence near the 5' end unique to the testicular mRNA.     

Evaluation of genotoxicity of clofazimine, an antileprosy drug, in mice in vivo. II. Micronucleus test in bone marrow and hepatocytes

The antileprosy drug, clofazimine, was tested for its possible genotoxicity using micronucleus (MN) tests in mice. A significantly higher incidence of MN in bone marrow erythrocytes, particularly in polychromatic erythrocytes, as well as in regenerated hepatocytes revealed a positive clastogenic effect of the drug. The drug also had a marked antimitotic effect as indicated by a negative correlation with the dose.