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Thiazole-4-carboxamide adenine dinucleotide (TAD), the active metabolite of the oncolytic C-nucleoside tiazofurin (TR), is susceptible to phosphodiesteratic breakdown by a unique phosphodiesterase present at high levels in TR-resistant tumors. Since accumulation of TAD, as regulated by its synthetic and degradative enzymes, appears to be an important determinant for sensitivity to the drug, a series of hydrolytically resistant phosphonate analogues of TAD were synthesized with the intent of producing more stable compounds with an ability to inhibit IMP dehydrogenase equivalent to TAD itself. Isosteric phosphonic acid analogues of TR and adenosine nucleotides were coupled with activated forms of AMP and TR monophosphate to give dinucleotides 2 and 4. Coupling of protected adenosine 5'-(alpha, beta-methylene)diphosphate with isopropylidene-TR in the presence of DCC afforded compound 3 after deprotection. These compounds are more resistant than TAD toward hydrolysis and still retain potent activity against IMP dehydrogenase in vitro. beta-Methylene-TAD (3), the most stable of the TAD phosphonate analogues, produced a depletion of guanine nucleotide pools in an experimentally induced TR-resistant P388 tumor variant that was superior to that obtained with TR in the corresponding sensitive line.

The nucleotide sequence of the tetracycline resistance gene tetM encoded by streptococcal conjugative shuttle transposon Tn1545 has been determined. The resistance gene was identified as a coding sequence of 1917 base pairs corresponding to a protein with a Mr of 72,500 daltons. This value is in good agreement with that, 68,000 daltons, estimated by SDS-polyacrylamide gel electrophoresis of Escherichia coli minicell extracts. The tetM gene product does not exhibit any sequence homology with either the Gram-negative (tetA, tetB and tetC), or the Bacillus and Staphylococcus tetracycline resistance proteins. The average hydropathy value of the tetM gene product (-0.21) contrasts with those calculated for the other TET proteins which are markedly hydrophobic (0.76 to 0.93). Hybridization experiments performed with an intragenic tetM probe do not support the claim [Taylor, D. (1986), J. Bact. 165, 1037-1039)] that tetracycline resistance in Campylobacter is due to acquisition of tetM.

Selected parameters of the haemostatic system were evaluated in 12 consecutive cases of canine Cushing's syndrome. The dogs did not exhibit evidence of thromboembolic complications. Levels of factors V and X were increased significantly (P less than 0.01) and fibrinogen concentration was increased modestly (P less than 0.05) in these dogs. Levels of factors IX and VIII:C remained in the reference range. Antithrombin III (ATIII) and plasminogen concentrations were markedly elevated (P less than 0.001). The low factor VIII:C and elevated ATIII levels in the plasma were not consistent with characteristics of a hypercoagulable state. These results demonstrated that haemostatic abnormalities which occur in canine Cushing's syndrome do not necessarily represent a state predisposed to thrombosis.

Tre character of K+ uptake in anaerobically grown S. typhimurium LT-2 is studied. In the alkaline media with glucose and moderate K+ activity these bacteria uptake K+ in two steps, the first of which has a high rate of K+ uptake, Km 2.1 mM and Vmax 0.44 mM/g. min and is sensitive to the medium osmolarity. Bacteria transfer from the media with high osmolarity to that with low one leads to a decrease of K+ uptake at the first step. The second increase of the medium osmolarity turns on the rapid K+ uptake only at alkaline pH. K+ uptake at the first step is inhibited by DCC and protonophores. In the absence of phosphate in the medium arsenate blocks K+ uptake at the first step, and when phosphate is available arsenate decreases K+ uptake. Valinomycin decreases the rate of K+ uptake. K+ uptake at the first step in S. typhimurium proceeds via Trk-like system which requires for K+ uptake both ATP and delta mu H+.

Plasma antithrombin III (AT-III) levels were measured in 61 patients undergoing general surgery. The patients were randomly allocated to a test or a control group. The test group received 5000iu of subcutaneous heparin two hours before operation and then twelve hourly for seven days. The control group received subcutaneous saline. Plasma levels of AT-III and of heparin were estimated before operation, at two, four and six hours after heparin injection on the day of operation and thereafter before the morning injection on the first, third and sixth postoperative days. Antithrombin III decreased progressively during and after operation in both groups. The decrease was greater in the test group at six hours after the first injection. These findings support the hypothesis that AT-III is consumed during coagulation and its utilization is increased in the presence of heparin.