The aminoacylation of transfer ribonucleic acid. Inhibitory effects of some amino acid analogues with altered side chains.

Several amino acid analogues that are able to replace amino acid residues in binding positions of the biologically active C-terminal tetrapeptide amide sequence, Trp-Met-Asp-PheNH2, of the gastrins were examined for their ability to inhibit the aminoacylation of tRNA in an Escherichia coli and rat liver system. Although in both systems the amino acid side chains are involved in the recognition process, the structural requirements of the side chain in the two systems are not comparable. Analogues of methionine and phenylalanine behaved similarly in the E. coli and rat liver systems, whereas analogues of tryptophan behaved differently. From the results it is possible to suggest structural features of the amino acid side chains which are required for recognition by the aminoacyl-tRNA synthetases.     

The carriage of Candida albicans in the mouths of rats treated with tetracycline briefly or for a prolonged period

Rats given tetracycline in their drinking water for one week were orally inoculated with Candida albicans in the following week. Colonization of the mouth by the fungus resulted, whether the rats continued to receive tetracycline or not, over a period of 22 weeks. Histological changes indicative of oral candidosis were also found both in rats maintained on tetracycline throughout the experiment and in animals given the drug only initially. It is suggested that exposure to tetracycline as tested in this experiment causes a lasting reduction in the rat's ability to expel C. albicans, or an enhancement of the organism's colonizing propensities.     

Experimental study of changes in osteoblastic shape induced by calcitonin and parathyroid extract in an organ culture system

Summary Neonate rat endocranial osteoblasts were cultured on their bone surfaces in control medium (CC) or medium to which either parathyroid extract (PTE) or calcitonin (CT) had been added for 2, 4, 8 or 24 h. Some were cultured for 24 h in CC, then for 2, 4, 8 or 24 h in either CT or PTE medium; or for 24 h in PTE, then for 2, 4, 8 or 24 h in either CC or CT; or 24 h in CT and 2, 4, 8 or 24 h in CC. The dorsal ruffling of the cells in CC was found to be suppressed by later culturing with PTE and the disoriented cells reorganized to form arrays of parallel cells. The effects of PTE were also reversed by CC or CT: the osteoblasts in the second culture (CC) lost elongation and order, and proceeded through a proliferative phase before exhibiting the ruffling form similar to a single CC 24 h culture. PTE-cultured osteoblasts showed an increase in cell overlap and contact so that a more competent barrier was formed separating the bone from the medium. In control or CT medium, however, intercellular gaps were greater than in vivo.We are grateful for the expert technical assistance of Elaine Bailey, for laboratory facilities kindly provided by Dr. Martin Evans, and for financial support from the Medical Research Council     

Local cold exposure of Andean Indians during normal and simulated activities.

Thermal resonses of Andean Indians were measured during several customary tasks associated with cold exposure in the highlands of southern Peru. These included surface temperature measurements of women while they washed clothing in the river and similar measurements of men while they constructed a diversion channel in the same river. A third test measured the effects of alcohol consumption on body temperatures during light activity. Women maintained slightly warmer hand than foot temperatures. Men maintained nearly equal hand and foot temperatures during the exposure period. Among male subjects the foot rewarmed at a faster rate than the hand. The results from the field studies compared favorably with results from earlier laboratory exposure tests. Comparisons between the river water exposure tests for males and females showed a consistent pattern where females maintained warmer hand and foot temperatures than males. These findings were in accord with previous laboratory studies among Quechua Indians and with the findings reported for other ethnic groups who experience natural cold stress. Alcohol ingestion appeared to have minimal effect in mitigating cold stress response during light activity. This finding was counter to earlier laboratory tests of resting subjects.     

Hexokinase isoenzymes in tissues of the adult and developing guinea pig

Changes in the activities and isoenzyme distribution of hexokinase were determined in a number of tissues during the development of the guinea pig. The total activity in the fetal liver showed a large fall during the second half of gestation to reach adult values by term. With normal diet the fetal, neonatal, and adult livers had isoenzymes I and III but little or no detectable IV (glucokinase). The fetal liver had predominantly type I, but the proportion of type III increased during development. The kinetics of the guinea pig isoenzymes were similar to those reported for the rat. Two additional isoenzymes with mobility between I and II were detected in the fetal liver and blood. They appear to have kinetic properties similar to type I. Detectable liver glucokinase activity was induced by glucose administration to adult guinea pigs. The total activity in kidney, brain and skeletal muscle showed a postnatal rise while in the fetal heart it was high and declined after birth. These tissues contained predominantly type I with varying proportions of type III hexokinase. The ratio of particulate-bound to soluble hexokinase varied from tissue to tissue. All except the liver showed a significant increase in binding after birth. The changes are discussed in relation to the control of glucose utilization in the fetal and neonatal periods.     

Biosynthesis of chloramphenicol in Streptomyces sp. 3022a. Identification of p-amino-L-phenylalanine as a product from the action of arylamine synthetase on chorismic acid.

Products obtained from the action of arylamine synthetase on [G-14C]chorismic acid were fractionated by gel filtration and ion exchange column chromatography to yield a partially purified radioactive component with an arylamine function. From its ultraviolet absorption spectrum and thin-layer chromatographic behaviour the product was considered to be p-aminophenylalanine and the identification was confirmed by co-crystallization with an authentic specimen. Specific deamination of the product with L-amino-acid oxidase indicated that it was the L-epimer. These results strengthen previous evidence that arylamine synthetase is at a branch point in the shikimic acid pathway, specifically diverting intermediates to the synthesis of chloramphenicol.     

Active observation in management of acute abdominal pain in childhood.

Out of 363 children admitted to a surgical unit with acute abdominal pain only 126 (35%) had an operation. Of these, 20 first underwent a period of "active observation." This procedure, used to help reach a diagnosis or decision in doubtful cases, is safe and useful and may be applied at home or in hospital.     

Role of doxapram in reducing pulmonary complications after major surgery.

In a double-blind study patients given a single dose of doxapram 1-5-2-0 mg/kg combined with morphine postoperatively had a significantly lower incidence of reflex postoperative cough and expectoration of purulent sputum than patients given morphine alone. They also had significantly higher arterial oxygen tensions five days postoperatively. Smaller differences were found with naloxone combined with morphine.