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Biomedical subjects

D Krause

Publications and source records attributed to D Krause.

At least 163 records · Page 9Linked to original sources

Regulation of ppp(A2'p)nA-dependent RNase levels during interferon treatment and cell differentiation.

The intracellular effector oligonucleotides ppp(A2'p)nA (n = 2- greater than or equal to 4) regulate the breakdown of RNA by activating ppp(A2'p)nA-dependent RNase. Cellular levels of this RNase were demonstrated to be regulated during differentiation of murine embryonal carcinoma cells. An induction of this RNase by interferon was demonstrated in each of three differentiated cell types (F9 clone 9, PYS, and PSA 5E) by analyzing rRNA breakdown following the introduction of ppp(A2'p)nA into the intact cells. In contrast, in three undifferentiated embryonal carcinoma cell lines (F9, PC13 clone 5, and Nulli 2A) there was little if any ppp(A2'p)nA-dependent RNase either with or without interferon pretreatment. These results were confirmed by affinity labeling of the RNase in cell-free systems. Addition of the proteinase inhibitor, leupeptin, to the cell lysis buffer was necessary to stabilize the RNase against cleavage to discrete breakdown products. Moreover, during differentiation of PC13 clone 5 cells by retinoic acid and N6,O2'-dibutyryl-adenosine 3',5'-monophosphate there was a gradual induction of ppp(A2'p)nA-dependent RNase. The expression of this RNase is, therefore, greatly enhanced during cell differentiation. In addition, the double-stranded-RNA-dependent protein kinase was investigated and was found to be interferon-inducible in all of the cell lines regardless of the state of cell differentiation.

Affinity Labels↗

Interferon-induced 2'-5' oligoadenylate synthetase during interferon-alpha therapy in homosexual men with Kaposi's sarcoma: marked deficiency in biochemical response to interferon in patients with acquired immunodeficiency syndrome.

Titers of circulating interferon (IFN) and the activity of 2'-5' oligoadenylate (2-5A) synthetase, an enzyme specifically induced by IFN, were measured in 28 homosexual men with acquired immunodeficiency syndrome (AIDS) who received one- to six-month courses of antineoplastic therapy with IFN-alpha and in homosexual and heterosexual controls. Fifteen of the patients and two of seven healthy homosexual men had high endogenous levels of 2-5A synthetase. IFN therapy induced further increases in this enzyme in only 10 of the 28 patients with AIDS. Furthermore, peripheral blood cells from all but one of the patients with AIDS and homosexual controls tested were markedly deficient in their ability to respond to IFN in vitro, as measured by increased levels of 2-5A synthetase. We did not find a statistical correlation between cytomegalovirus viremia and pretherapy endogenous circulating IFN, nor any apparent correlation between disseminated infection with cytomegalovirus and either basal levels of 2-5A synthetase or changes in enzyme level during therapy. Pretherapy circulating IFN was significantly correlated with progressive Kaposi's sarcoma during therapy, but rises in levels of 2-5A synthetase were not sufficient to predict a good clinical response.

2',5'-Oligoadenylate Synthetase↗

Thrombogenicity of central venous catheters: prospective study of polyethylene, silicone and polyurethane catheters with phlebography or post-mortem examination.

The thrombogenicity of polyethylene, silicone and polyurethane central venous catheters was compared in a prospective clinical, phlebographic and post-mortem study in 52 patients. The incidence of central venous thrombosis was high with polyethylene catheters (70%), but much lower with silicone (20%) and with polyurethane catheters (17%).

Catheters, Indwelling↗

[Diagnostic angiography of antero-apical ventricular aneurysms. Contribution of multiple projections. Apropos of 42 cases].

The wide variety of definitions covering the term, left ventricular aneurysm, at the present time suggests the need for a radiological description based on pathological findings. The presence of the aneurysm on angiographic images is shown by a persistent left ventricular deformity during diastole causing a pocket separated from the contractile left ventricle by an annular constriction. A study of 42 cases of anterior apical ventricular aneurysms selected according to these criteria and investigated by multiple ventriculographic projections (LAO, RAO, anteroposterior and profile) demonstrated that the right anterior oblique projection alone is insufficient to ensure the diagnosis. An indirect sign suggestive of the diagnosis is a double outline due to the superimposition of aneurysmal and contractile zones. A complementary LAO projection, with or without a profile film, should be performed in order to confirm diagnosis and determine extent of lesion, this conditioning the result of surgery.

Angiography↗

Interferon-induced synthesis of 2-5A-dependent RNase in mouse JLS-V9R cells.

Interferon treatment of mouse JLS-V9R cells resulted in a 10- to 20-fold increase in the levels of the 2-5A (ppp(A2'p)nA)-dependent RNase. The nuclease was monitored in cell extracts by covalent and noncovalent binding of 32P-labeled 2-5A derivatives to the nuclease and by the appearance of 2-5A-mediated ribosomal RNA cleavage products. Untreated JLS-V9R cells contained very low levels of the nuclease (5-10% of that found in control Ehrlich ascites tumor cells). An increase in the nuclease was first detected between 3 and 6 hr after interferon treatment and was completely inhibited by actinomycin D. Control experiments indicated that the increase in the nuclease was not due to an intracellular redistribution of the enzyme. The results indicate that in JLS-V9R cells, interferon controls the activity of the 2-5A system at two levels: by inducing the synthesis of both the 2-5A-dependent RNase and the 2-5A-synthetase.

2',5'-Oligoadenylate Synthetase↗

Induction of ppp(A2'p)nA-dependent RNase in murine JLS-V9R cells during growth inhibition.

We recently reported that interferon induces the synthesis of ppp(A2'p)nA(n = 2 to greater than or equal to 4) (2-5A)-dependent RNase in the murine cell line JLS-V9R. These cells normally contain very low levels of the nuclease; after interferon treatment, however, they develop levels approaching those found in murine L or Ehrlich ascites tumor cells. Here, we report a similar increase in the nuclease levels in JLS-V9R cells during the transition from the subconfluent actively growing state to the confluent stationary phase. Levels of 2-5A synthetase increased in parallel with the nuclease. The induced levels of both the nuclease and synthetase returned to low basal amounts after trypsinization, dilution, and culturing of the cells at subconfluent densities. The addition of anti-murine interferon (alpha + beta) antibodies to the medium did not affect the induction of the nuclease nor could any interferon be detected in the culture supernatants as determined by the lack of antiviral activity. The increase in the enzymes was not, therefore, due to the spontaneous production of interferon. The induction of the nuclease during confluency preceded an inhibition of [3H]-thymidine incorporation by the cells into DNA. The regulation of the 2-5A-dependent RNase in JLS-V9R cells may, therefore, be related to the control of cell growth.

2',5'-Oligoadenylate Synthetase↗

Estimation of Rate constant from measurement during free dosage regimen.

The estimation procedure for pharmakokinetic rate constants of blood and/or urine levels which have been taken during a free dosage regimen is described under the assumption of a classical open two-compartment model of first order. In an example phenylbutazone concentration measurements are used to demonstrate the iteration estimation procedure and to discuss the specific problems in order to receive unbiased and best estimates. Advantages and disadvantages of multiple-dose studies in free dosage regimen are itemised, and model functions for the free dosage regimen are suggested.

Humans↗