Beta adrenergic receptors and cyclic AMP levels in intact human lymphocytes: Effects of age and gender

A saturable, stereospecific high affinity beta₂ adrenergic receptor was demonstrated on intact human peripheral blood lymphocytes using the ligand [¹²⁵I]-iodocyanopindolol ([¹²⁵I]ICYP). A method is described for parallel measurements of saturation binding isotherms and isoproterenol-cAMP responsiveness in split samples of intact lymphocytes isolated from 40 ml. of whole blood. A significant positive correlation between beta receptor density (Bmax) and the ratio of maximal isoproterenol-generated cAMP to basal levels was found in healthy subjects (r=0.65, p < 0.001). A significant positive correlation was found between age and the fold increase over basal cAMP levels induced by isoproterenol. Older females had a significantly higher fold increase in cAMP levels after isoproterenol than older males. These effects were largely accounted for by the lower basal levels of cAMP in older subjects. Beta receptor binding indices (Bmax and K_D) did not differ between males and females, or change with aging. The effects of age and sex upon cAMP levels appear to be at least partly mediated by mechanisms independent of the beta receptor. The method, which describes a convenient assay for parallel measurement of beta receptor binding and cAMP levels in small blood samples, represents a useful model for studying human beta receptor function.     

Use of a Continuous Glucose Monitoring System in High-Risk Hospitalized Noncritically Ill Patients With Diabetes After Cardiac Surgery and During Their Transition of Care From the Intensive Care Unit During COVID-19: A Pilot Study

ObjectiveContinuous glucose monitoring (CGM) has demonstrated benefits in managing inpatient diabetes. We initiated this single-arm pilot feasibility study during the COVID-19 pandemic in 11 patients with diabetes to determine the feasibility and accuracy of real-time CGM in patients who underwent cardiac surgery and whose care was being transitioned from the intensive care unit.MethodsA Clarke error grid analysis was used to compare CGM and point-of-care measurements. The mean absolute relative difference (MARD) of the paired measurements was calculated to assess the accuracy of CGM for glucose measurements during the first 24 hours on CGM, the remaining time on CGM, and for different chronic kidney disease (CKD) strata.ResultsOverall MARD between point-of-care and CGM measurements was 14.80%. MARD for patients without CKD IV and V with an estimated glomerular filtration rate (eGFR) of ≥20 mL/min/1.73 m² was 12.13%. Overall, 97% of the CGM values were within the no-risk zone of the Clarke error grid analysis. For the first 24 hours, a sensitivity analysis of the overall MARD for all patients and those with an eGFR of ≥20 mL/min/1.73 m² was 15.42% ± 14.44% and 12.80% ± 7.85%, respectively. Beyond the first 24 hours, overall MARD for all patients and those with an eGFR of ≥20 mL/min/1.73 m² was 14.54% ± 13.21% and 11.86% ± 7.64%, respectively.ConclusionCGM has shown great promise in optimizing inpatient diabetes management in the noncritical care setting and after the transition of care from the intensive care unit with high clinical reliability and accuracy. More studies are needed to further assess CGM in patients with advanced CKD.     

Cellular pathophysiology of cystic kidney disease: insight into future therapies.

Polycystic kidney disease (PKD) is a developmental kidney disorder which can be inherited as either an autosomal dominant trait, with an incidence of 1:50 to 1:1000, or as an autosomal recessive trait with an incidence of 1:6,000 to 1:40,000. Three different genes have now been cloned that are associated with mutations that cause PKD. Two of these are linked to the most common forms of the dominant disease while the third is associated with the orpk mouse model of recessive polycystic kidney disease. Advances in understanding the molecular genetics of PKD have been paralleled by new insights into the cellular pathophysiology of cyst formation and progressive enlargement. Current data suggest that a number of PKD proteins may interact in a complex, which when disrupted by mutations in PKD genes may lead to altered epithelial proliferative activity, secretion, and cell matrix biology. The identification of a unique cystic epithelial phenotype presents new opportunities for targeted therapies. These include targeted gene therapy, gene complementation, and specific immunological or pharmacological interruption of growth factor pathways.     

Wild-Type Strain of Staphylococcus aureus Containing Two Genetic Linkage Groups for Penicillinase Production

Staphylococcus aureus strain 55C1, isolated from a patient in 1955, contained two genetic linkage groups for penicillinase formation. One was linked to genes that control resistance to cadmium and mercuric ions; it had properties of a plasmidborne gene. The other was not linked to resistance to these metal ions; it had properties of a chromosomal gene. Penicillinase formation by cells that contained either linkage group was inducible by penicillins. Induced penicillinase in cells that contained both linkage groups equalled the sum of that produced in cells containing each group singly. Exopenicillinase produced by cells containing either gene was serological type A. Constitutive penicillinase formation resulting from regulator gene mutations in either linkage group was repressed to differing extents by a wild-type determinant in the trans position. The genetic structure and the regulation of penicillinase formation in strain 55C1 resembled in general those for penicillinase linkage groups which Asheshov and Dyke described for diploid mutant strains of S. aureus PS 80. There were differences in detail, however.     

Formation of amino acids by cobalt-60 irradiation of hydrogen cyanide solutions.

Aqueous solutions of hydrogen cyanide (0.004-0.1 M) were exposed to cobalt-60 gamma rays. Among the products formed on hydrolysis of the irradiated solution; glycine, alanine, valine, serine, threonine, aspartic acid, and glutamic acid have been identified.     

The lack of a solvent accessible hydroxide or water ligand to iron at the 3Fe center of Azotobacter vinelandii ferredoxin I

The X-ray crystal structure of Azotobacter vinelandii ferredoxin I (FdI) describes a planar 3Fe-3S center in which one of the iron atoms is ligated to a solvent accessible oxo ligand, presumably from water or hydroxide (Ghosh et al., (1982) J. Mol. Biol. 158, 73-109). Efforts to displace the proposed oxo ligand with cyanide were unsuccessful, even in 80% dimethylsulfoxide. In addition, comparison of the electron spin echo envelopes for H2O- and D2O-equilibrated samples of FdI showed only a slight deuterium modulation, far less than would be expected were water to be bound as an iron ligand. These results do not support the presence of a solvent accessible oxo ligand to the 3Fe center as described in the X-ray crystal structure.     

Decrease in hepatic cytochrome P-450 and catalase following allylisopropylacetamide: The effect of concomitant hemin administration

It is known that administration of allylisopropylacetamide (AIA) to rats increases δ-aminolevulinic acid synthetase (ALA-S), urine ascorbic acid excretion and decreases hepatic hemoproteins cytochrome P-450 and catalase. Hemin has been shown to inhibit induction of ALA-S by AIA. To investigate further the regulatory role of hemin, AIA was administered to rats over a 5 day period with and without hemin. Hemin did not prevent the decrease in P-450 or catalase caused by AIA but partially inhibited induction of ALA-S and the increase in ascorbic acid excretion. It is unlikely that the hemin is replacing endogenous heme in hemoprotein synthesis and we conclude that the role of hemin in suppressing induction phenomena that follow AIA treatment reflects a regulatory function not related to a role in hemoprotein synthesis.