The structure of hemoglobin Creteil (beta 89 Ser replaced by Asn) is similar to that of abnormal human hemoglobins having sequence changes at Tyr 145 beta

In normal deoxyhemoglobin A, the beta chain COOH-terminal peptide adopts a well ordered structure which is needed for the full expression of allosteric action. Our crystallographic studies of deoxyhemoglobin Creteil (beta 89 Ser replaced by Asn), a variant hemoglobin characterized by high oxygen affinity and a very low level of allosteric function, show that replacement of Ser 89 beta by asparagine causes severe disordering of the beta chain COOH-terminal tetrapeptide. This results, as shown by our spectroscopic studies, in the destabilization of the quaternary structure of deoxyhemoglobin Creteil. We find, furthermore, that the changes in tertiary structure observed in deoxyhemoglobin Creteil are common to other variant hemoglobins having similar functional abnormalities but very different changes in primary structure. In particular, direct comparison of the difference electron density map of deoxyhemoglobin Creteil with that of deoxyhemoglobin Nancy (beta 145 Tyr replaced by Asp) suggests that these two abnormal hemoglobins may have the same mechanism of dysfunction despite the very different nature of their respective sequence changes.     

Vanadate,alcohol or both increase passive membrane permeability of neuro-2a cells; Lesser sensitivity of Hep-2 cells

Neuro-2a cells incubated for 1 hour with 0.1 mM vanadate showed an increase in cell membrane permeability. This effect is dose dependent, e.g. with 0.01 mM, 0.1 mM and 1 mM vanadate, there was {20, 30 and 40% increase. In contrast, no alteration in permeability was observed in HEp-2 cells under the same conditions.Ethanol (3%, 1 h incubation) also enhanced membrane permeability. The increase was also greater with Neuro-2a cells ({80%) than with HEp-2 cells (～30%). When the cells were incubated with ethanol plus vanadate (0.1 mM), there was a marked potentiation ({200%) in cell membrane permeability in Neuro-2a cells, and again a lesser increase in permeability ({50%) with HEp-2 cells.These results seem to be due to a preferential effect of vanadate on passive permeability of Neuro-2a cells because parallel measurements demonstrate equal inhibition of (Na⁺K) ATPase with both Neuro-2a and HEp-2 cells.     

Intraaortic administration of protamine: Method for heparin neutralization after cardiopulmonary bypass

In neutralizing heparin with intravenous protamine sulfate, hypotension may be prevented by administering the drug intraarterially. Forty patients underwent cardiac surgery with extracorporeal circulation in our hospital; each received a rapid injection of nondiluted protamine sulfate in the aortic root to reverse the effects of heparin. To maintain the blood volume at a constant level, volume expanders and inotropic drugs were avoided. The intraaortic injections ranged in duration from 0.2 min to 2.8 min, with a mean of 1.1 min. The mean systolic pressure only dropped from 92 mm Hg (SD +/- 21) before protamine injection to 85 mm Hg (SD +/- 23) after injection (p < 0.0001). In seven patients (18%), no hypotension was evident; in the remaining patients, the systolic pressure returned to preinjection values within a mean of 2.2 min. Coagulation was observed within 3 to 4 min (mean = 2.2 min) after the initiation of injection. This study indicates that intraaortic administration of protamine is a rapid and safe technique for heparin reversal after cardiopulmonary bypass.     

Structural regularities in tetraether lipids of Caldariella and their biosynthetic and phyletic implications

Individual di(biphytanyl) diglycerol tetraether lipids from thermoacidophile archaebacteria of the Caldariella series, with differently cyclized biphytanyl components, are separated and shown to have structures 8–12, with the glycerol and biphytanyl components demonstrably both antiparallel and with partial assignments of stereochemistry. Tetraethers with alternative arrangements of the components are absent. The structures allow previous observations on these and related lipids to be rationalized both biosynthetically and phyletically.     

Human Ia molecules carrying DC1 or BR4X7 determinants are not homologous to murine I-E molecules

An anti-I-E^k alloantiserum was shown to react with purified human Ia preparation. All Ia preparations tested were actively bound irrespective of their HLA-DR phenotypes. However, from a quantitative point of view, DR7 molecules were significantly less reactive. No reaction was observed with isolated Ia subunits. Only molecules carrying DR determinants, but not those carrying either DC1 or BR4X7 determinants, were bound.     

The ATP/2e ratio during photosynthesis in intact spinach chloroplasts.

Addition of ribose-5-phosphate to intact spinach chloroplasts in the absence of added P_i resulted in a conversion of part of the Benson-Calvin cycle into a linear sequence so that triose phosphate accumulated during CO₂ fixation stoichiometrically with the O₂ evolved (triose phosphate / O₂ ratio was 2.0). The fortunate consequence of this effect is that the $\text{ATP}\text{2e}$ ratio may be calculated from the 3-phosphoglycerate and triose phosphate accumulated and the O₂ evolved. In this way the $\text{ATP}\text{2e}$ ratio was shown to be 2.0, with cyclic or pseudocyclic phosphorylation contributing less than 9% to the total phosphorylation.     

Photocross-linking analysis of the contact surface of tRNA Met in complexes with Escherichia coli methionine:tRNA ligase.

Photoinduced covalent cross-linking has been used to identify a common surface of four methionine-accepting tRNAs which interact specifically with the Escherichia coli methionine:tRNA ligase (EC 6.1.1.10). tRNA--ligase mixtures were irradiated, and the covalently linked complexes were isolated and digested with T1 RNase (Schimmel & Budzik, 1977). The fragments lost from the elution profile of the T1 RNase digest were considered to have been cross-linked to the protein and therefore in intimate contact with the enzyme. Only specific cognate tRNA--ligase pairs produce covalently linked complexes. The four substrate tRNAs used in this study have substantially different sequences, but all showed a common cross-linking pattern, supporting the view that the sites cross-linked to the enzyme reflect the functionally common contact surface rather than particularly photoreactivity regions of tRNA. The cross-linked contact surface is comprised of three regions: (1) the narrow groove of the anticodon stem and its extension into the anticodon loop; (2) the 3' terminal residues; and (3) the 3' side of the "T arm". Unlike previous studies with other tRNAs, the D arm is not involved and significant radiation damage is suffered by the tRNA which must be taken into account in the analysis. The results are consistent with and complement chemical modification studies [Schulman, L. H., & Pelka, H. (1977) Biochemistry 16, 4256].     

Hemoglobin J Cairo: beta 65 (E9) Lys leads to Gln, A new hemoglobin variant discovered in an Egyptian family.

The present report describes clinical, hematological and biochemical studies of a 27-year old Egyptian woman in whom a fast moving Hb variant was found. The abnormal Hb constituted 48% of the total erythrocyte Hb of the propositus and her father. Structural studies demonstrated that in the abnormal Hb lysine beta 65 is replaced by glutamine. The new Hb mutant is designated hemoglobin J Cairo beta 65 (E9) Lys leads to Gln. This substitution results in only a moderate decrease in cooperativity. No evidence of Hb instability was found. A slight anemic state has been observed in the propositus since she reached adolescence.     

Sea-blue histiocytosis and beta-thalassemia in the same family.

Among 5 families with SBH of Neapolitan origin, herediatry glyco-lipidosis was accompanied in one by beta-thalassemia. All 10 members of this family, namely parents and 8 siblings, were investigated. The mother and two children were found to be carriers of both SBH and beta-thalassemia, while three other siblings were carriers of SBH alone. None of the six patients conformed the classic clinical picture often observed in genotypical SBH. The present state of genotypic transmission of the stigma is discussed on the basis of the author's experience as well as the data in the literature. As for the combination SBH-thalassemia in the same individual it may be concluded that the two genes are most likely independent and certainly not linked.