Cerebral glycine content and phosphoserine phosphatase activity in hyperaminoacidemias

Chronic hyperphenylalaninemia maintained with the aid of a suppressor of phenylalamine hydroxylase, -methylphenylalanine, increases the glycine concentration and the phosphoserine phosphatase activity of the developing rat brain but not that of liver or kidney. Similar increases occur after daily injections with large doses of phenylalanine alone, while tyrosine, isoleucine, alanine, proline, and threonine, were without effect. Treatment with methionine, which increases the phosphoserine phosphatase activity of the brain and lowered that of liver and kidney, left the cerebral glycine level unchanged. When varying the degrees of gestational or early postnatal hyperphenylalaninemia, a significant linear correlation was found between the developing brains' phosphoserine phosphatase and glycine concentration. Observations on the uptake of injected glycine and its decline further indicate that coordinated rises in the brain's phosphoserine phosphatase and glycine content associated with experimental hyperphenylalaninemia denote a direct impact of phenylalanine on the intracellular pathway of glycine synthesis in immature animals.     

Radiation-induced cardiomyopathy in the dog

Sequential necropsies and histologic evaluations of young adult beagle dogs were performed after irradiation of the thorax. Total doses to the heart were 36, 44, or 52 Gy given in 4-Gy fractions in 4 weeks. One month after irradiation there was little histologic evidence of damage visible by light microscopy. However, ventricular and septal weights were increased, probably due to edema. At 3 months damage to endothelial and mesothelial cells was evident. By 12 months the myocardium was thinned and focal degeneration and loss of muscle cells and Purkinje fibers were observed. There was extensive subendocardial and epicardial fibrosis as well as intimal proliferation in coronary arteries. Morphometric analyses were performed on the myocardium, pericardium, atria, and aorta. There was a slight increase in perivascular connective tissue in the myocardium. The pericardium was increased in thickness and the ratio of smooth muscle to elastin was decreased in the aorta. Severe fibrosis occurred only in the right atrium. At 1 year there was no clinical evidence of heart failure; however, evidence of myocardial damage was present histologically and functionally. Additional stress and continued aging are likely to enhance the damage and lead to serious complications. The interactions of irradiated lung and heart require further investigation.     

High level of divergence of male-reproductive-tract proteins, between Drosophila melanogaster and its sibling species, D. simulans

We compared male-reproductive-tract polypeptides of Drosophila melanogaster and D. simulans by using two-dimensional gel electrophoresis. Approximately 64% of male-reproductive-tract polypeptides were identical between two randomly chosen isofemale lines from these two species, compared with 83% identity for third-instar imaginal wing-disc polypeptides. Qualitatively similar differences were found between reproductive tracts and imaginal discs when D. sechellia was compared with D. melanogaster and with D. simulans. When genic polymorphism was taken into account, approximately 10% of male- reproductive-tract polypeptides were apparently fixed for different alleles between D. melanogaster and D. simulans; this proportion is the same as that found for soluble enzymes by one-dimensional gel electrophoresis. Strikingly, approximately 20% of male-reproductive- tract polypeptides of either D. melanogaster or D. simulans had no detectable homologue in the other species. We propose that proteins of the Drosophila male reproductive tract may have diverged more extensively between species than have other types of proteins and that much of this divergence may involve large changes in levels of polypeptide expression.      

Trehalose dimycolate enhances survival of fission neutron-irradiated mice and Klebsiella pneumoniae-challenged irradiated mice

The survival of B6D2F1 female mice exposed to lethal doses of fission neutron radiation is increased when trehalose dimycolate (TDM) preparations are given either 1 h after exposure or 1 day before exposure to radiation. TDM in an emulsion of squalene, Tween 80, and saline was the most effective formulation for increasing the 30-day survival of mice when given 1 day before (90%) or 1 h after (88%) exposure to radiation. An aqueous suspension of a synthetic analog of TDM was less effective at increasing 30-day survival (60%) when given 1 day prior to radiation exposure and not effective when given 1 h after radiation. Mice receiving a sublethal dose (3.5 Gy) of fission neutron radiation and either the TDM emulsion or synthetic TDM 1 h after irradiation were substantially more resistant to challenge with 10, 100, 1000, or 5000 times the LD50/30 dose of Klebsiella pneumoniae than untreated mice.     

Microbial transformation of primaquine by Candida tropicalis.

The microbial metabolism of primaquine, a 6-methoxy-8-aminoquinoline antimalarial agent, was investigated. The yeast Candida tropicalis was found to convert primaquine to the previously reported N-acetylated derivative. On continued incubation of C. tropicalis in the presence of the N-acetylated derivative, a minor dimeric metabolite was formed. The proposed structure of the metabolite was based primarily on the analysis of its spectroscopic properties (1H and 13C nuclear magnetic resonance spectra and field-desorption mass spectrum). The structure of the metabolite was proven by direct comparison with an authentic sample of the minor dimeric metabolite prepared by treatment of the N-acetylated derivative with formaldehyde in the presence of formic acid in methanol.     

Production of a novel dimeric metabolite of primaquine by Streptomyces rimosus.

Primaquine, an 8-amino-6-methoxyquinoline antimalarial agent, was subjected to metabolic studies with microorganisms. Streptomyces rimosus converted primaquine to the previously reported N-acetyl derivative. Continued incubation of S. rimosus resulted in the formation of a minor dimeric metabolite. The structure of the minor dimeric metabolite was proposed based primarily on its spectral data (1H and 13C nuclear magnetic resonance spectra and mass spectrum). The proposed structure of the metabolite was confirmed by synthesis of the dimer by treatment of primaquine-N-acetate with potassium ferricyanide in a biphasic chloroform-aqueous sodium bicarbonate system with a phase-transfer catalyst. Since (+/-)-primaquine was used for both the microbial transformation and synthesis, a diastereomeric mixture of symmetrical dimers was formed in each case. The metabolite sample was identical to the synthetic sample, as shown by direct comparison (thin-layer chromatography, co-thin-layer chromatography, high-pressure liquid chromatography, co-high-pressure liquid chromatography, 1H nuclear magnetic resonance spectra, and mass spectrum).     

Pre-induction priming of the uterine cervix with oral prostaglandin E2 and a placebo

A double blind study was undertaken to determine the effectiveness or oral prostaglandin E2 as a means of improving the pelvic score prior to induction of labour. 48 patients who were greater than 37 were gestation and who had Bishop scores of less than 6 entered the study. Ten tablets were given on an hourly regime. Of 25 patients in the prostaglandin group, 17 were considered successes (68.0%), whereas of 23 patients who received a placebo, 9 were successes (39.1%). No adverse effects were recorded. Prostaglandin E2 is therefore considered a safe and effective method for priming the unfavourable cervix prior to induction of labour.     

Monoclonal antibodies to rabbit liver cytochrome P-448

Cytochrome P-448 (mol wt 55,000 Daltons) from rabbit liver was purified to a specific content of 16.6 nmol/mg. Mice were immunised with this preparation, their spleens removed and dissociated lymphocytes hybridised with myeloma cells. Four monoclonal antibodies against cytochrome P-448 were raised and partially characterised. All four antibodies interacted with cytochrome P-448 in intact microsomal fractions and selectively immunoadsorbed cytochrome P-448 from solubilised microsomal preparations. One of the antibodies inhibited benzo[a] pyrene hydroxylase activity in a reconstituted system, one had no effect on activity and two increased activity. The possible applications of such antibodies are discussed.