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H L Cailla

Publications and source records attributed to H L Cailla.

18 recordsLinked to original sources
PubMed1988

Mechanisms of degradation of 2'-5' oligoadenylates.

We have studied the mechanisms of breakdown of 2'-5' oligoadenylates. We monitored the time-courses of degradation of ppp(A2'p5')nA (dimer to tetramer) and of 5'OH-(A2'p5')nA (dimer to pentamer) in unfractionated L1210 cell extract. The 5' triphosphorylated 2'-5' oligoadenylates are converted by a phosphatase activity. However, 2'-5' oligoadenylates are degraded mainly by phosphodiesterase activity which splits the 2'-5' phosphodiester bond sequentially at the 2' end to yield 5' AMP and one-unit-shorter oligomers. The nonlinear least-squares curve-fitting program CONSAM was used to fit these kinetics and to determine the degradation rate constant of each oligomer. Trimers and tetramers, whether 5' triphosphorylated or not, are degraded at the same rate, whereas 5' triphosphorylated dimer is rapidly hydrolyzed and 5'-OH dimer is the most stable oligomer. The interaction between degradation enzymes and the substrate strongly depends on the presence of a 5' phosphate group in the vicinity of the phosphodiester bond to be hydrolyzed; indeed, when this 5' phosphate group is present, as in pp/pA2'p5'A/or A2'/p5'A2'p5'A/, affinity is high and maximal velocity is low. Such a degradation pattern can control the concentration of 2'-5' oligoadenylates active on RNAse L either by limiting their synthesis (5' triphosphorylated dimer is the primer necessary for the formation of longer oligomers) and/or by converting them into inhibitory (e.g., monophosphorylated trimer) or inactive (e.g., nonphosphorylated oligomers) molecules.

Adenine Nucleotides↗
PubMed1987

The occurrence of 2'-5' oligoadenylates in Escherichia coli.

The use of a highly specific radioimmunoassay and of HPLC permitted us to confirm the occurrence of 2'-5' oligoadenylates [p chi (A2'p5')nA] in several strains of Escherichia coli. Cellular concentrations of 2'-5' oligoadenylates ranged from 50 nM to 300 nM. The mixture of 2'-5' oligoadenylates consisted primarily of pppA2'p5'A, pA2'p5'A,A2'p5'Ap and A2'p5'A under normal conditions of growth. None of them activated RNase L. Infection of the bacteria with the single-stranded DNA phage M13 or induction of a heat-inducible, non-lytic mutant of phage lambda led to a significant increase in the total pool of 2'-5' oligoadenylates, paralleling the progressive inhibition of growth. Likewise, the inhibition of protein synthesis with chloramphenicol stimulated the accumulation of 2'-5' oligoadenylates. Furthermore, the inhibition of bacterial growth by either phage or by chloramphenicol brought about a change in the composition of the 2'-5' oligoadenylate pool; 5'-phosphorylated 2'-5' oligoadenylates accumulated and became the major components. The findings indicate a parallelism between the effects of viral infection on the synthesis of 2'-5' oligoadenylates in eukaryotes and similar effects subsequent to phage growth in the bacterium E. coli.

Adenine Nucleotides↗
PubMed1981

Relationship between the levels of cyclic cytidine 3':5'-monophosphate, cyclic guanosine 3':5'-monophosphate, and cyclic adenosine 3':5'-monophosphate in urines and leukocytes and the type of human leukemias.

Cyclic cytidine 3':5'-monophosphate (cyclic CMP), cyclic guanosine 3':5'-monophosphate (cyclic GMP), and cyclic adenosine 3':5'-monophosphate (cyclic AMP) contents of leukocytes and urines of leukemic patients have been investigated. We have studied four types of leukemia: acute myeloblastic leukemia; chronic myelocytic leukemia; acute lymphoblastic leukemia; and chronic lymphocytic leukemia. As controls, the cyclic nucleotide content of leukocytes and urines of healthy volunteers and patients with solid tumors selected for their normal hemogram has been determined. It has also been measured in phytohemagglutinin-stimulated lymphocytes. Our data show that: (a) the concentration of cyclic CMP is always lower than that of cyclic GMP or cyclic AMP; (b) in urines, the concentrations of the three nucleotides are higher in patients than in healthy volunteers, the greatest differences being observed between the cyclic CMP concentrations of acute leukemia patients and controls; and (c) in white blood cells, cyclic AMP concentration is lower in leukemic than in normal cells. The cyclic GMP concentration is the same everywhere except in monoblastic cells and leukocytes from solid tumor patients. High cyclic CMP levels are associated only with acute leukemia, whether myeloblastic, monoblastic, or lymphoblastic, a fact which suggests that cyclic CMP could be a biochemical marker of hematopoietic stem cell malignancy.

Adult↗
PubMed1979

Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin-pancreozymin.

The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin-pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg-1 h-1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg-1 h-1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg-1 h-1 of CCK and later for 12 and 24 U kg-1 h-1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.

Animals↗
PubMed1976

Endogenous cyclic AMP in thyroid cell culture. Effect of thyroid-stimulating hormone and dibutyryl cyclic AMP.

We have studied the variations of endogenous cyclic AMP levels in thyroid cells cultured over a period of 7 days in several conditions: in the presence of thyroid-stimulating hormone or dibutyryl cyclic AMP which both promote the aggregation of isolated cells into follicles, and in their absence when cells develop as a typical monolayer. In follicle-forming cells, the cyclic AMP level was found to rise during the first day of culture, then to fall rapidly. In monolayer-forming cells, the cyclic AMP content slightly increases attaining the same level as found in other cells at the fourth day, which remains stable till the seventh day. We have investigated the response of these cells cultured in the presence of dibutyryl cyclic AMP retain the capability of increasing their cyclic AMP concentration whereas monolayer-forming cells do not preserve this quality of thyroid cells.

Animals↗
PubMed1976

Effect of sugars on early biochemical events in development of Dictyostelium discoideum.

Metabolizable sugars blocked development of the slime mold Dictyostelium discoideum; the same sugars also inhibited the formation of contact sites "A", of membranal 3':5'-cyclic adenosine monophosphate (cAMP)-binding sites, and of total cAMP phosphodoesterase (3':5'-cyclic-nucleotide phosphodiesterase; EC 3.1.4.17; 3':5'-cyclic-nucleotide 5'-nucleotidohydrolase). These inhibitory effects of the sugars on the synthesis of cellular components, required for the aggregation of developing amebae, were paralleled by an inhibition of the accumulation of cAMP which normally accompanies development. The inhibition by sugars could be overcome partially by pulsing the amebae with nanomolar concentrations of cAMP only after the amebae had acquired cAMP-binding sites. The findings suggest that metabolizable sugars inhibit development by blocking the formation of cAMP and, conversely, that development in D. discoideum may be related to the energetic state of the cell.

3',5'-Cyclic-AMP Phosphodiesterases↗