Gene Literature Dashboard

The autopsy and electron microscopic findings in a pair of brothers with congenital dyserythropoietic anemia (CDA) are presented. In both patients autopsy revealed severe secondary hemochromatosis, including cirrhosis of the liver and fatal heart involvement. According to current ultrastructural criteria, a mixture of CDA type I (interchromatin bridges, wide euchromatin-cytoplasmic connections) and of type II (marginal cisternae, nuclear protrusions, multinuclearity, karyorrhexis) was found in erythroblasts of one patient. In the second patient electron microscopy of bone marrow stored in formalin for several years allowed the diagnosis of CDA with marginal cisternae in retrospect. These findings illustrate the usefulness of electron microscopy for the diagnosis of CDA in unsolved cases of chronic ineffective erythropoiesis, even from formalin fixed material. For subtyping CDA into type I and II, however, other than morphological parameters should be used for definition. In the clinical management splenectomy and a drastic phlebotomy programme have been found favourable.

Membranes of Escherichia coli contain an adenosine 5'-triphosphate (ATP) energy-transducing system that is inhibited by treatment with dicyclohexylcarbodiimide (DCCD). The carbodiimide-reactive protein component of this system has been identified after treatment with [14C]DCCD. This protein has an apparent molecular weight of 9,000 as judged from acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and is extracted from the membrane with chloroform-methanol (2:1). These properties are similar to the analogous protein previously identified in mitochondria (Cattell et al., 1971). A mutant strain, RF-7, has been isolated which derives energy from oxidative phosphorylation in the presence of 5 mM DCCD. The ATP hydrolase activity of the membraned system in the mutant was considerably less sensitive to inhibition by DCCD than that in the wild type. The carbodiimide-reactive protein, which was easily labeled by [14C]DCCD in the wild type, was labeled much less rapidly in the carbodiimide-resistant mutant. It is thus concluded that the reaction of DCCD with this specific protein leads to inhibition of the ATP energy-transducing reactions. The mutation causing carbodiimide resistance in strain RF-7 was mapped. It is cotransduced with the uncA gene at a frequency exceeding 90%. The mutationally altered protein causing the carbodiimide resistance was not conclusively identified. However, reconstitution experiments indicate that the altered protein is not one of the subunits of the soluble ATP hydrolase activity, which can be removed from the membrane by washing with 1 mM tris(hydroxymethyl)aminomethane buffer lacking Mg2+. The carbodiimide-reactive protein remains with the membrane residue after removal of the soluble ATP hydrolase and is thus distinct from these subunits as well.

The reaction of pig pepsin and pepsinogen with 3H-dicyclohexylcarbodiimide (DCC-T) is studied. It is found that about three residues of DCC-H incorporate into pepsin molecule and about four residues--into pepsinogen molecule under the excess of carbodiimide. The incorporation of DCC-T into protein results in a deep enzyme and zymogen inactivation: pepsine retains 20% of the proteolytic activity with respect to hemoglobin, and pepsinogen completely loses its potential proteolytic activity. It is found that a part of DCC-T residues attaches to N-terminal part of pepsinogen, which splits off under the activation of proenzyme in acid medium. It is demonstrated that the interaction of DCC-T with carboxyl groups of dicarbonic amino acids results in the change of isoelectric point of pepsin and pepsinogen.