Gentamicin and amikacin repress the growth of Plasmodium falciparum in culture, probably by inhibiting a parasite acid phospholipase

Human erythrocytes were loaded with either gentamicin or amikacin and subsequently infected with the human malarial parasite Plasmodium falciparum and grown in culture. Parasite invasion of erythrocytes was unaffected by the drugs, but subsequent development was retarded. The digestion of host cell cytosol in ring-stage parasites was inhibited by the drugs. A substantial acid, Ca2+-independent phospholipase activity could be monitored in parasite cytosol and was found to be inhibited by the drugs. These results imply that phospholipases are involved in the feeding mechanism of the parasite and that gentamicin and amikacin exert their inhibitory activity by affecting these enzymes.     

A specific decrease in collagen synthesis in acutely fasted, vitamin C-supplemented, guinea pigs

Weight loss often results from various experimental conditions including scurvy in guinea pigs, where we showed that decreased collagen synthesis was directly related to weight loss, rather than to defective proline hydroxylation (Chojkier, M., Spanheimer, R., and Peterkofsky, B. (1983) J. Clin. Invest. 72, 826-835). In the study described here, this effect was reproduced by acutely fasting normal guinea pigs receiving vitamin C, as determined by measuring collagen and non-collagen protein production after labeling tissues in vitro with [3H]proline. Collagen production (dpm/microgram of DNA) decreased soon after initiating fasting and by 96 h it had reached levels 8-12% of control values. Effects on non-collagen protein were much less severe, so that the percentage of collagen synthesis relative to total protein synthesis was 20-25% of control values after a 96-h fast. These effects were not due to changes in the specific radioactivity of free proline. Refeeding reversed the effects on non-collagen protein production within 24 h, but collagen production did not return to normal until 96 h. The effect of fasting on collagen production was independent of age, sex, ascorbate status, species of animal, and type of connective tissue and also was seen with in vivo labeling. Pulse-chase experiments and analysis of labeled and pre-existing proteins by gel electrophoresis showed no evidence of increased collagen degradation as a result of fasting. Procollagen mRNA was decreased in tissues of fasted animals as determined by cell-free translation and dot-blot hybridization with cDNA probes. In contrast, there was no decrease in translatable mRNAs for non-collagen proteins. These results suggest that loss of nutritional factors other than vitamin C lead to a rapid, specific decrease in collagen synthesis mainly through modulation of mRNA levels.     

Influence of chronic antigen exposure on the metabolism of PGH2 by microsomal preparations of airway and parenchymal tissues in the sheep

The effects of repeated antigen exposure on the synthesis of mediators by lung tissues are not well understood. To investigate the influence of antigen challenge on the synthesis of prostaglandins by central airway and peripheral lung tissues, fourteen sensitive sheep underwent biweekly exposure to aerosolized $\text{Ascaris suu}$ antigen (7) or saline (7). Following the fifth exposure, microsomal and high speed supernatant fractions were prepared from trachealis muscle and lung parenchyma. Synthesis of thromboxane (TX) A₂, prostaglandin (PG) D₂ and PGI₂ from the PG endoperoxide intermediate, PGH₂, was assayed over a range of substrate concentrations from 3–200 uM. Synthesis of PGI₂ by trachealis microsomes was approximately 5-fold greater than that of TXA₂. PGI₂ and TXA₂ production was identical in tracheal preparations from Ascaris- and saline-exposed animals. In parenchymal tissues, where TXA₂ production predominated over PGI₂ by 9-fold, preparations from Ascaris- exposed animals synthesized 50% more TXA₂ than controls at PGH₂ concentrations of 25 uM and above, whereas synthesis of PGI₂ and PGD₂ were similar in preparations from both groups of animals. The density of pulmonary mast cells was decreased by 21% in the Ascaris group, whereas polymorphonuclear leukocyte density was unchanged. These results demonstrate the differential synthesis of TXA₂ and PGI₂ in central airways and peripheral lung regions of the sheep. They further indicate that repeated exposure of the airways to antigen selectively enhances TXA₂ synthesis in the lung periphery of sensitized animals. The site of this increased enzymatic activity, whether in resident cells or newly-infiltrated cells, has not been determined.     

Phenotype frequencies of vitamin D binding protein (Gc) and of posttransferrin-2 (Ptf-2) in Belgian cattle breeds*

The vitamin D binding protein (Gc) and posttransferrin-2 (Ptf-2) phenotypes have been determined in a number of Belgian cattle breeds. A very slow migrating variant of the Gc protein — Gc C — has been found in White and Red East Flemish breed. This variant was absent from the other breeds studied. This slow variant was identified as a vitamin D binding protein by autoradiography. The Gc C protein was shown to be controlled by a codominant autosomal allele Gc C at the Gclocus. The Gc C protein is probably identical with a fraction previously described in buffalo and an Italian cattle breed. The allele frequencies for the Gc and Pft-2 systems are reported for several Belgian breeds of cattle.     

Comparison of estrogen priming effects with body weight restoration effects on the gonadotropin pattern of patients with anorexia nervosa

Plasma estradiol (E2), serum LH and FSH, and the gonadotropin response to two consecutive LHRH administrations (10 and 100 micrograms with an interval of 2 h) were determined in 19 patients with anorexia nervosa (AN) at the emaciation phase, before and after estradiol benzoate (E2B) injections (3 micrograms/kg/day for 7 days). The same investigations were repeated after weight restoration in 9 AN patients who remained amenorrheic. Both at the emaciation phase and after weight restoration, E2B enhanced the second LH response to LHRH and decreased serum FSH, suggesting that the functional capacities of the pituitary gonadotrophs are normal in AN. Unlike E2B injections, weight restoration increased all the hormone values, suggesting that the weight restoration effects on the abnormal gonadotropin secretory pattern of AN depend on another mechanism than the E2 lowering. That mechanism is probably a disorder of the hypothalamic LHRH secretion, the consequences of which could be reinforced by the low E2 levels.     

Tunicamycin-resistant mutants of Bacillus amyloliquefaciens are deficient in amylase, protease and penicillinase synthesis and have altered sensitivity to antibiotics and autolysis

Mutants of Bacillus amyloliquefaciens resistant to at least 10 micrograms/ml of tunicamycin were isolated and shown to be pleiotropic. The mutants were more resistant to streptomycin, chloramphenicol, kanamycin and neomycin than was the parent strain but less resistant to penicillin G and tetracycline. They were more autolytic, presumably due to an altered cell wall. The mutants produced reduced levels of amylase, penicillinase and both metal and serine protease besides having an enhanced sporulation frequency and being more motile.     

Estimate of mean tissue O2 consumption at onset of exercise in males

A mathematical model has been developed that permitted the calculation of the flow-weighted mean tissue O2 consumption (VO2T) at the onset of a step increase in work rate. From breath-by-breath measurements of alveolar O2 consumption (VO2A) and cardiac output (Q) by impedance cardiography and assumptions about the site of depletion of O2 stores, the rate of change in O2 stores (VO2s) was determined. The sum of VO2A + VO2s = VO2T. Six very fit males performed six repetitions of each of two step increases in work rate. STlo was a transition from rest to 100-W cycling; SThi was a transition from 100- to 200-W cycling. For each work rate transition, the responses of VO2A and Q were averaged over the six repetitions of each subject and the model was solved to yield VO2T. The responses of VO2A, VO2T, and Q after the increase in work rate were fit with a monoexponential function. This function included a time constant and time delay, the sum of which gave the mean response time (MRT). In the STlo test, the MRT of VO2A (24.9 +/- 1.1 s, mean +/- SE) was longer than that of VO2T (15.3 +/- 1.3 s) and of Q (16.5 +/- 6.5 s) (P less than 0.05). The MRT of VO2T and Q did not differ significantly. Also for SThi, the MRT of VO2A (34.4 +/- 3.3 s) was significantly longer than that of VO2T (30.0 +/- 3.4 s) (P less than 0.05). The MRT of VO2T and Q (30.3 +/- 5.5 s) were not significantly different at this work rate either.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inositol 1,4,5-trisphosphate is not effective in releasing calcium from skeletal sarcoplasmic reticulum microsomes

Regulation of many cell systems has been shown to be mediated by Inositol 1,4,5-trisphosphate which causes a release of calcium from intracellular sites. We have shown that release of Ca2+ from sarcoplasmic reticulum microsomes was not stimulated by IP3. The phorbol ester, TPA, also had no effect on Ca2+ release or Ca2+ ATPase activity. Thus, it is unlikely that the breakdown of polyphosphatidylinositides serves as a second messenger to mediate release of Ca2+ in skeletal muscle.