Use of an ammonia electrode to study bacterial deamination of amino acids with special reference to D-asparagine breakdown by campylobacters.

A method using an ammonia electrode is being developed for investigating the deamination of amino acids and amides by bacteria. Application of this method to Campylobacter jejuni and C. coli has led to the demonstration of D-asparaginase activity in some strains. This has allowed the subdivision of both species into D-asparaginase-positive and -negative biotypes. Even though the method is in the developmental stage, it was found to be generally reproducible and easy to perform. Areas for further improving the procedure have been identified. The ammonia electrode offers the theoretical possibility of investigating the breakdown of any amino acid by bacteria. It thus opens up a new and practical approach for separating species and strains, particularly in those bacterial groups that are difficult to subdivide by conventional means.     

Toxoplasma encephalitis in a HIV patient: unusual involvement of the corpus callosum

In patients with acquired immuno-deficiency syndrome, the differential diagnosis between primary brain lymphoma and toxoplasma encephalitis is not radiologically always straightforward, especially in the presence of a solitary cerebral lesion. In this context, involvement of the corpus callosum is almost exclusively associated with primary brain lymphoma. We describe here an HIV-infected patient who presented with a single and large cerebral lesion affecting the corpus callosum, suggestive of primary brain lymphoma on MRI-scan but who nonetheless responded clinically and radiologically to an anti-toxoplasma drug trial confirming the diagnosis of toxoplasma encephalitis.     

Effects of 1,25-dihydroxyvitamin D3 and cortisol on bovine and human parathyroid cells

Incubation of bovine parathyroid cells with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) decreased both preproparathyroid mRNA levels and parathyroid hormone (PTH) secretion. There was a fall to 56.6 +/- 13.7% (mean +/- S.E.M.) and 65.1 +/- 9.3% in mRNA levels and PTH secretion respectively at 1 nmol 1,25-(OH)2D3/l, and 41.1 +/- 13.6% and 42.0 +/- 12.1% at 10 nmol 1,25-(OH)2D3/l after 24 h. After 48 h in 0.1 nmol 1,25-(OH)2D3/l, mRNA levels had fallen to 35.3 +/- 12.6% and PTH secretion to 32.1 +/- 5.0%. In human adenomatous cells, however, incubation with 1,25-(OH)2D3 (10 nmol/l) had no effect on either mRNA levels or PTH secretion even after 48 h. This lack of sensitivity of adenomatous cells to 1,25-(OH)2D3 was not due to an absence of receptors (3847 +/- 39 receptors/ng cytosolic protein in adenomatous cells compared with 4068 +/- 371 in bovine cells) or receptors being of low affinity. Cortisol (1 mumol/l) caused a reduction in the number of receptors for 1,25-(OH)2D3 in bovine parathyroid cells of approximately 20% within 24 h of incubation, but no change in affinity. This decrease was accompanied by abolition of the response to 1,25-(OH)2D3 and was reversible, in that withdrawal of cortisol for the final 24 h of incubation was sufficient for the response to return, the number of receptors having returned to control values. These results suggest that only a small percentage of receptors for 1,25-(OH)2D3 in bovine parathyroid cells may be functional at any one time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abortion and perinatal sepsis associated with campylobacter infection

Fetal loss or neonatal sepsis associated with campylobacter infection during pregnancy is infrequently recognized. As reported herein, one case of premature labor and neonatal sepsis due to Campylobacter fetus subspecies fetus was treated successfully with ampicillin and gentamicin. Only 19 similar cases have been cited in the literature. A review of these 19 cases reveals that the Campylobacter species involved were probably C. fetus subspecies fetus in nine instances, Campylobacter jejuni in nine, and Campylobacter coli in one. There were no significant species-related differences in clinical presentation or outcome. Eighteen of 20 pregnancies (including tht described herein) ended prematurely at 13-32 weeks of gestation. All of the mothers survived, but fetal/neonatal mortality was 80%. The pathogenesis of campylobacter infection in this situation probably involves maternal bacteremia originating from the bowel, with subsequent feto-placental involvement. Early recognition and treatment may improve fetal/neonatal outcome.     

Clostridium difficile invasion and toxin circulation in fatal pediatric pseudomembranous colitis.

The direct involvement of Clostridium difficile in the lesional tissue of pseudomembranous colitis has not been demonstrated; the organism's effects have been assumed to be strictly toxin mediated. Because C. difficile cytotoxin may be found incidentally in the intestinal lumina of asymptomatic infants, the role of the organism in a variety of pediatric intestinal diseases is uncertain. The authors studied seven cases of fatal pediatric pseudomembranous colitis in which the presence of C. difficile was uniformly demonstrable in lesional tissues with the use of both an intestinal spore stain and a specific immunostain. The patients had either underlying Hirschsprung's disease or hematologic malignancy; the striking pathologic features peculiar to these patients were altered mucosal mucin and immunologic barriers in the former group and neutropenia in the latter. Two patients had demonstrable circulating cytotoxin in serum or ascitic fluid, and C. difficile was identified invading colonic mucosa or submucosa. Such phenomena did not occur in control pediatric patients with multiple other intestinal lesions. Altered host factors may be responsible for the intestinal invasion of C. difficile and its systemic toxin circulation in cases of fatal pediatric pseudomembranous colitis.     

The Cancer Genome Atlas Analysis Predicts MicroRNA for Targeting Cancer Growth and Vascularization in Glioblastoma

Using in silico analysis of The Cancer Genome Atlas (TCGA), we identified microRNAs associated with glioblastoma (GBM) survival, and predicted their functions in glioma growth and progression. Inhibition of two “risky” miRNAs, miR-148a and miR-31, in orthotopic xenograft GBM mouse models suppressed tumor growth and thereby prolonged animal survival. Intracranial tumors treated with uncomplexed miR-148a and miR-31 antagomirs exhibited reduced proliferation, stem cell depletion, and normalized tumor vasculature. Growth-promoting functions of these two miRNAs were, in part, mediated by the common target, the factor inhibiting hypoxia-inducible factor 1 (FIH1), and the downstream pathways involving hypoxia-inducible factor HIF1α and Notch signaling. Therefore, miR-31 and miR-148a regulate glioma growth by maintaining tumor stem cells and their niche, and providing the tumor a way to activate angiogenesis even in a normoxic environment. This is the first study that demonstrates intratumoral uptake and growth-inhibiting effects of uncomplexed antagomirs in orthotopic glioma.