Low-molecular-weight Ia antigens in normal mouse serum

Low-molecular-weight Ia antigens can be detected in mouse serum. A procedure for isolating these antigens from serum in high yield is described. The Ia antigen preparation was found to be rich in carbohydrate, low in protein, and strongly bound to Concanavalin A andLotus lectins. Furthermore, the Ia antigenicity was destroyed by periodate oxidation and neuraminidase treatment, but was unaffected by pronase. These observations strongly suggest that the Ia antigens in serum are oligosaccharide in nature. Such a conclusion implies that at least some of the genes in theI region of theH-2 gene complex code for glycosyl transferase enzymes.     

Neoaplectana glaseri: essential amino acids

Required for a nematode's reproduction in a chemically defined medium are the nine mammalian essential amino acids (sensu strictu). Needed in addition to lysine, tryptophane, histidine, phenylalanine, leucine, isoleucine, threonine, methionine, and valine is arginine which is marginally essential for mammals. Tyrosine, nonessential for mammals, is not absolutely required by the nematode but is beneficial in terms of onset time and quantity of reproduction. Aspartic acid, nonessential for the nematode and mammals, is toxic for adult nematodes at and above 4.8 mg/ml medium. The nematode, Neoaplectana glaseri, is parasitic in insect grubs but the strain used has been cultivated in species isolation on kidney slices continuously since (1944).     

THE RELATIONSHIP OF THE REFERRING PHYSICIAN TO THE PSYCHIATRIST

Tumors of the adrenal glands produce hormones which cause a variety of symptoms and signs including high blood pressure, excessive growth of hair on the body and precocious sexual development. By recently developed tests, it has been possible to differentiate high blood pressure due to these tumors from hypertension due to other causes. Removal of these tumors will often alleviate changes caused by them. Localization of the tumor and appraisal of the condition of the contralateral gland should be carried out preoperatively if possible. In this, several kinds of roentgen studies are helpful. Infusions of drugs during operation can be used to control the blood pressure which otherwise would vary widely. During a ten-year period (1942 to 1951) there were observed at the Los Angeles County General Hospital 100 proved cases of non-secreting and secreting primary neoplasms of the adrenal glands. In addition, there were three cases of Cushing's syndrome due to bilateral adrenal cortical hyperplasia, and ten probable cases (four, pheochromocytomas; five, Cushing's syndrome; one, adrenogenital syndrome) in which operation was not done.     

Interaction between the soluble F1 ATPase and its naturally occurring inhibitor protein. Studies using hydrophilic high-performance liquid chromatography and immunoelectron microscopy

Binding of the isolated ATPase (F1) to its naturally occurring inhibitor protein was studied by two novel, independent techniques. High-pressure gel permeation chromatography revealed one tight binding site (Kd = 0.46 microM) for the inhibitor on F1, and a number of weak, non-specific sites. Use of an antibody directed against a non-binding region of the inhibitor protein demonstrated the formation of inhibitor/F1/immunoglobulin G complexes of 1:1:1 and 2:2:1 stoichiometry, but not of the putatively more stable cyclic 4:2:2 complexes. It was concluded that, despite the presence of three beta-subunits, only one site per F1 molecule is available for binding its inhibitor protein.     

Different half-lives of messenger RNA corresponding to different segments of the tryptophan operon of Escherichia coli

In genetically derepressed strains (trpR⁻) of Escherichia coli which are growing exponentially, messenger RNA regions corresponding to different segments of the trp operon are labeled with different kinetics, suggesting that operator-proximal and distal regions of trp-mRNA have different half-lives. This conclusion was confirmed by direct measurement of trp-mRNA decay; the half-lives for different mRNA regions at 30 °C were found to be 60 seconds for trpE-mRNA, 75 seconds for trpDC-mRNA, and 95 to 115 seconds for trpBA-mRNA. Deletions of genetic segments within the operator-proximal region of the operon reduce the half-life of trp BA-mRNA. Large deletions which place the BA region near the operator reduce the half-life of trpBA-mRNA to values similar to that of trpE-mRNA in the parental strain. Therefore location in the message rather than primary structure appears to determine the half-life of each mRNA region. Several of the internal deletions have a polar effect on the synthesis of the trpB and trpA polypeptides. However, the reduction in trpBA-mRNA half-life does not appear to be due to polarity because trpBA-mRNA half-life is reduced to the same value in three deletion mutants in which there is a sevenfold difference in polarity. These results are compatible with a model of trp-mRNA degradation in which the initial degradative event occurs near the 5′ end of the mRNA molecule and is followed by over-all degradation in the 3′ direction, with random or non-random delays causing an increase in half-life of about 10% per 1000 nucleotides mRNA. Our findings are not compatible with a model of normal degradation in which the entire mRNA molecule is the target for the initial degradative event.     

Covalent Bonding of Pyrrolobenzodiazepines (PBDs) to Terminal Guanine Residues within Duplex and Hairpin DNA Fragments

Pyrrolobenzodiazepines (PBDs) are covalent-binding DNA-interactive agents with growing importance as payloads in Antibody Drug Conjugates (ADCs). Until now, PBDs were thought to covalently bond to C2-NH₂ groups of guanines in the DNA-minor groove across a three-base-pair recognition sequence. Using HPLC/MS methodology with designed hairpin and duplex oligonucleotides, we have now demonstrated that the PBD Dimer SJG-136 and the C8-conjugated PBD Monomer GWL-78 can covalently bond to a terminal guanine of DNA, with the PBD skeleton spanning only two base pairs. Control experiments with the non-C8-conjugated anthramycin along with molecular dynamics simulations suggest that the C8-substituent of a PBD Monomer, or one-half of a PBD Dimer, may provide stability for the adduct. This observation highlights the importance of PBD C8-substituents, and also suggests that PBDs may bind to terminal guanines within stretches of DNA in cells, thus representing a potentially novel mechanism of action at the end of DNA strand breaks.