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Biomedical subjects

J Franke

Publications and source records attributed to J Franke.

At least 145 records · Page 8Linked to original sources

Developmental regulation of the cyclic-nucleotide-phosphodiesterase mRNA of Dictyostelium discoideum. Analysis by cell-free translation and immunoprecipitation.

Extracellular cyclic-nucleotide phosphodiesterase of Dictyostelium discoideum has previously been purified and characterized [Orlow et al. (1981) J. Biol. Chem. 256, 7620-7627]. Antisera have been raised against the purified enzyme. Following cell-free translation of RNA extracted from cells at various stages of development and immunoprecipitation with anti-phosphodiesterase serum, cAMP phosphodiesterase synthesized in vitro and labeled with L-[35S]methionine can be detected by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and fluorography. The cell-free translation product is an Mr-48 000 polypeptide and can be immunoprecipitated with antiserum raised against active Mr-50 000 cAMP phosphodiesterase or antiserum raised against heat-denatured cAMP phosphodiesterase. Purified native cAMP phosphodiesterase blocks immunoprecipitation of the cAMP-phosphodiesterase polypeptide synthesized in vitro. A detectable level of cAMP-phosphodiesterase mRNA is present in axenically grown cells. After starvation of the cells in phosphate buffer for 1 h an increase of translatable cAMP-phosphodiesterase mRNA occurs, followed by a decrease and another increase. When cells are starved in the presence of the slowly hydrolyzed cAMP analogue, adenosine 3',5'-thiophosphate, the level of translatable cAMP-phosphodiesterase mRNA increases about tenfold and does not show a temporary decline. A maximum of 0.015% of the total acid-insoluble radioactivity is incorporated into the Mr-48 000 cAMP-phosphodiesterase polypeptide.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Effect of fluoride on the skeletal system].

The chronic fluoride intoxication in man and animal may cause so different diseases of the bones as osteosclerosis, osteomalacia, secondary hyperparathyroidism and osteoporosis--partly in combination. On the basis of own examinations and of literature an own theory is developed which tries to explain these 4 contrary findings on the bone. According to this theory the fluor dosage, the calcium and vitamin D deficiency, differences of the species, duration of the fluoride supply and an individual sensitiveness to fluoride play an important role. Fluor has an effect on the 3 constituents of bones: osteoblasts, osteoclasts and the bone material.

Age Factors↗

Pressure effects and uptake of platelet-activating factor in isolated rat lung.

The aim of this study was, first, to examine pressure effects of platelet-activating factor (PAF) on pulmonary vasculature and bronchi in isolated perfused and ventilated rat lungs and, second, to investigate pulmonary uptake of tritium-labeled PAF injected into the pulmonary artery. Four different perfusates were used: Krebs-Ringer solution (KRS) and KRS with 0.2, 2.0, and 4% albumin. In the KRS, perfusion and inflation pressure increased by 100 and 47%, respectively, after 100 micrograms PAF. By increasing the albumin concentration, the pressure effects were reduced significantly (P less than 0.01). These changes were paralleled by increasing tritium outflow rates (15.9 +/- 3.6, 49.7 +/- 12.5, 78.3 +/- 8.7, 87.8 +/- 2.6%, respectively). Comparable changes in tritium outflow rates (19.2 +/- 3.9, 38.2 +/- 7.2%) occurred when tracer amounts of labeled PAF were injected, but, in KRS with 2.0 and 4.0% albumin, tritium outflow was significantly lower (52.8 +/- 8.0 and 60.8 +/- 11.8%, respectively). Pressure effects are related to extraction rates. Both pressure effects and extraction rates depend on binding to the albumin in the perfusion medium used. PAF might act on smooth muscle tissue of the pulmonary vasculature. Inflation pressure increases are probably due to concomitant occurrence of edema.

Animals↗

[Avulsion fractures of the foot].

The avulsion (strain) fractures of the foot can be divided into two groups. Indications for conservative or operative treatment are discussed in detail.

Foot Injuries↗

Detection and regulation of the mRNA for the inhibitor of extracellular cAMP phosphodiesterase of Dictyostelium discoideum.

The inhibitor of the cAMP phosphodiesterase of Dictyostelium discoideum is a cysteine-rich glycoprotein, which binds to the enzyme and inactivates it. When the inhibitor is removed, enzymatic activity is restored. Following translation in vitro of RNA from developing cells and immunoprecipitation with anti-inhibitor serum, newly synthesized inhibitor can be detected by sodium dodecylsulfate/polyacrylamide gel electrophoresis and fluorography. The inhibitor can be labeled using [35S]cysteine but not [35S]methionine, in agreement with the previously determined amino acid composition, and can be detected after cell-free translation only if it has been previously acetylated. Purified native inhibitor blocks immunoprecipitation of the inhibitor polypeptide synthesized in vitro. No inhibitor mRNA was detected in growing cells. Translatable mRNA was present 2 h after the beginning of starvation, reached a maximal level after 3 h, and decreased thereafter. Addition of 1 mM cAMP at the beginning of starvation delayed the appearance of translatable inhibitor mRNA. In the presence of 5 microM adenosine cyclic-3',5'-phosphorothioate, a slowly hydrolyzed cAMP analogue, no translatable mRNA could be detected. Following removal of the analogue, the mRNA appeared within one hour and inhibitor was secreted after another hour.

3',5'-Cyclic-AMP Phosphodiesterases↗

Kinetics of 57Co-bleomycin in sheep after intra-arterial injection in the head and neck region.

Intra-arterial (i.a.) chemotherapy for the treatment of head and neck tumors is performed on the basis of clinical reports. The hypothetical aim of i.a. chemotherapy is to achieve higher drug concentrations in the tumor than are achieved by systemic intravenous (i.v.) administration. Therefore, it is postulated that i.a. chemotherapy leads to an increased therapeutic effect at the tumor site and to a decrease in systemic drug toxicity. The lack of adequate animal experiments and the absence of prospective randomized clinical trials comparing i.a. with i.v. chemotherapy led to the present kinetic study, concerned with various modes of administration of bleomycin with the aim of achieving high cytotoxic concentrations at the required site. Radioactive bleomycin (57Co-bleomycin) was injected locally (buccal plane, group I), intra-arterially (transverse facial artery, group II; superficial temporal artery, group III; external carotid artery, group IV), and intravenously (saphenous vein, group V) in five sheep per group. Between 1 and 360 min after injection of radioactive bleomycin the urine and the systemic blood activities were determined, and the activities in the hypothetical tumor area (buccal plane) were measured continuously. The animals were killed 360 min after injection and the activities in the hypothetical tumor area, in the lymph nodes draining this area (submandibular, parotic, lateral pharyngeal) and in different tissues and organs were determined. For all groups, 70%-80% of the injected bleomycin was eliminated by the kidneys, without any significant differences among the five groups tested. The systemic blood activities measured at 5-min intervals exhibited no differences for the groups injected i.a. (II-IV) and i.v. (V). Only animals which received local injections (group I) showed lower activities for 60 min after injection as compared with the other four groups. The activities of radioactively labeled bleomycin in the hypothetical tumor area during the entire experiment (360 min) were again similar for the groups injected i.a. (II-IV) and those injected i.v. (V). However, only animals injected locally (group I) showed significantly increased activities. After the death of the animals there was again no significant difference between i.a. and i.v. administration. Only local injection led to significantly increased tissue activities. Similar results also obtained for the lymph nodes draining the hypothetical tumor area.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Production and recovery of human leukocyte-derived alpha interferon using a cascade filtration system.

The use of a cascade filtration system for production and recovery of human leukocyte-derived alpha interferon (HuIFN-alpha) has been investigated. Included in the investigation were mass transfer studies of HuIFN-alpha across ultrafiltration membranes, design and evaluation of a laboratory-scale production system and determination of IFN production kinetics in both batch and filtration systems. The cascade filtration system allows separation of interferon from leukocytes and virus during production with simultaneous concentration and complete recovery. Kinetic studies indicate that HuIFN-alpha production can be enhanced by appropriate timing of the filtration procedure. While the current study is concerned with HuIFN-alpha, it is expected that the techniques developed will be applicable to the production and recovery of both natural and recombinant IFNs and lymphokines in general.

Cell Survival↗