Exercise activates renal dysfunction in hypertension.

A bilateral, exercise-mediated renal functional abnormality was first described more than a decade ago. The disturbance is specific for hypertension, is seen in different forms of hypertension, and has been studied most extensively in hypertensives with renovascular disease. The bilateral-abnormal exercise renogram identifies the disturbance.

Epitope analysis of the murine p53 tumour suppressor protein.

The identification and characterisation of the p53 tumour suppressor has relied extensively on the use of immunological reagents. To facilitate further characterisation of the murine p53 protein (Mp53), and its interaction with other proteins, we have characterised the antigenic sites of Mp53 in fine detail. Using an overlapping Mp53 peptide library we report the identification by Pepscan ELISA of the epitopes of nine antibodies.

Modification of an N-terminal regulatory domain of T antigen restores p53-T antigen complex formation in the absence of an essential metal ion cofactor.

We have discovered that the ability of the tumor suppressor protein p53 to bind to the viral large T antigen (TAg) oncogene product is regulated by divalent cations. Both proteins were purified from an insect cell line infected with the appropriate baculovirus expression vector. In a two-site capture enzyme-linked immunosorbent assay, complex formation between the purified proteins is strictly dependent on the addition of specific concentrations of divalent metal ions, notably zinc, copper, cadmium, cobalt, manganese, and nickel.

Allosteric regulation of the thermostability and DNA binding activity of human p53 by specific interacting proteins. CRC Cell Transformation Group.

Conformational stability is a prerequisite for the physiological activity of the tumor suppressor protein p53. p53 protein can be allosterically activated for DNA binding by phosphorylation or through noncovalent interaction with proteins such as DnaK, the Escherichia coli homologue of the heat shock protein Hsp70. We present in vitro evidence for a rapid temperature-dependent change in the conformation and tetrameric nature of wild-type p53 upon incubation at 37 degrees C, which correlates with a permanent loss in DNA binding activity.

[Dystopic goiter--aspects of definition and surgical therapy].

The incidence in the literature of dystopic goiter depends on classification of the false endothoracic goiter ("substernal goiter") as dystopic and varies from 2 to 20%. From November 1989 through April 1993 we operated on 530 patients with benign nodular goiters. In 84 patients (15.

Small peptides activate the latent sequence-specific DNA binding function of p53.

Normal cells contain p53 protein in a latent state that can be activated for sequence-specific transcription by low levels of UV radiation without an increase in protein levels. Microinjection of cells with an antibody specific to the C-terminal negative regulatory domain can activate the function of p53 as a specific transcription factor in the absence of irradiation damage, suggesting that posttranslational modification of a negative regulatory domain in vivo is a rate-limiting step for p53 activation. Small peptides derived from the negative regulatory domain of p53 have been used as biochemical tools to distinguish between allosteric and steric mechanisms of negative regulation of p53 tetramer activity.

Two distinct signaling pathways activate the latent DNA binding function of p53 in a casein kinase II-independent manner.

Post-translational modification of a carboxyl-terminal negative regulatory domain in vitro by either casein kinase II or protein kinase C allosterically activates the latent sequence-specific DNA binding function of p53. Reported here is a biochemical approach to determine the types of signaling pathways and enzymes that are involved in p53 activation in cells. Using a novel chromatographic method, we have been able to separate three distinct biochemical forms of p53 that have been synthesized in vivo; two are in an activated state, and one is in a latent state for sequence-specific DNA binding.

A direct effect of activated human p53 on nuclear DNA replication.

p53 is a transcriptional activator and repressor, but recent evidence suggests that some of its many biological functions may not be dependent on transcription. To determine whether p53 exerts a direct influence on nuclear DNA replication, purified human p53 was added to a transcription-free DNA replication extract from Xenopus eggs. Full-length human p53 that inhibits SV40 DNA replication in vitro had no effect on nuclear DNA synthesis in the Xenopus system.

[Endovascular and open reconstructive surgery of renal artery lesions].

Besides antihypertensive drug treatment and reconstructive surgery, the percutaneous transluminal angioplasty became an established treatment modality for renal artery stenosis since the late 70's. The treatment aimed at curing the renovascular hypertension, at normalizing and improving of both compensated and decompensated renal insufficiency in order to avoid prolonged hemodialysis after acute renal failure. Endovascular procedures contributed significantly to reach a normotensive state, particularly in cases with renal artery stenosis concomitant with fibromuscular dysplasia and gives similar results as open surgical methods if certain morphological features are considered.

On the regulation of the p53 tumour suppressor, and its role in the cellular response to DNA damage.

The p53 gene is required for the normal apoptotic response of mammalian cells to DNA damage caused by ionizing radiation and DNA damaging drugs. DNA damage results in the accumulation of biologically active p53. This response is potentially lethal and is therefore highly regulated.

[The sonographic and computed radiographic findings in perigraft reactions after the surgical implantation of vascular prostheses].

Between January 1988 and January 1994, 24 patients with heterologous vascular bypasses were examined with suspected diagnosis of a perigraft reaction (PGR). All patients were subjected to ultrasound and CT. PGR ist defined as a sterile inflammation along the course of a vascular prosthesis.

[Determination of the degree of stenosis of the internal carotid artery in the surgical specimen after eversion TEA: comparison with angiography and c-w-Doppler ultrasound].

Unlabelled: 22 carotid specimens following eversion-endarterectomy were compared with preoperative assessment of carotid stenosis obtained angiographically and by c-w-Doppler-sonography. The intact, unsplit specimens were perfused with a liquid plastic material (Palavit M). After hardening of the plastic material the specimens were removed.

Repeat exercise renograms in hypertension identify persistent renal dysfunction.

Background: Hypertensives may develop bilateral trapping of para-aminohippurate analogues in the tissue of the kidneys during light exercise, as can be demonstrated using radioactively labelled [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine. Tracer accumulation in the kidneys during exercise results in a typical renographic pattern, the bilateral-abnormal exercise renogram. The disturbance is common during exercise, being found in almost 60% of all hypertensives, regardless of aetiology.

Revision of the proximal aortic anastomosis after aortic bifurcation surgery.

The implantation of an aortic bifurcation graft (ABG) for treatment of occlusive (OD) and aneurysmal (AD) aortoiliac disease is a standard technique with good long-term results and a relatively low incidence of complications. In a retrospective review of our patients from 1964 to 1993 only 36/1520 patients were identified who required reoperation at the proximal aortic anastomosis after ABG. Indications were graft occlusion (15/36) and graft stenoses (2/36), refractory to graft thrombectomy, proximal aortic anastomotic aneurysms (11/36) or graft infection (8/36).

Allosteric activation of latent p53 tetramers.

Background: The DNA-binding activity of p53 is essential to its function as a tumour suppressor. Point mutations that abolish this activity have been found to occur frequently in the p53 genes of human cancer cells. Wild-type p53 protein assembles into oligomers with latent DNA-binding activity that can be activated in vitro by phosphorylation of a carboxy-terminal regulatory region, catalyzed by protein kinase C or casein kinase II.

The role of the p53 protein in the apoptotic response.

When mammalian cells or tissues are exposed to DNA damaging agents a programmed cell death pathway is induced as well as a cell cycle arrest. In mice in which the p53 gene has been inactivated by homologous recombination this response is profoundly diminished. These mice develop normally so that developmentally induced apoptotic events do not require p53.

Synthesis of DnaK protein during the division cycle of Escherichia coli.

DnaK protein is involved in the initiation of DNA synthesis from the Escherichia coli chromosome as well as from the replication origins of phage lambda and P1. The synthesis of dnaK mRNA and protein has been reported to vary during the cell cycle of Caulobacter crescentus (Gomes et al., 1990).

[Diagnosis and therapy of perioperative lung embolism].

Pulmonary embolism is a major cause of postoperative problems, accounting for 12-20% postoperative deaths. 0.1% to 0.

Regulation of the cryptic sequence-specific DNA-binding function of p53 by protein kinases.

p53 is an allosterically regulated protein with a latent DNA-binding activity. Posttranslational modification of a carboxy-terminal regulatory site in vitro, by casein kinase II and protein kinase C, can activate the sequence-specific DNA-binding function of the wild-type protein. The latent form of p53 is produced in a variety of eukaryotic and prokaryotic cell lines, including E.

[Nonocclusive intestinal ischemia as a complication of hemodialysis treatment].

A 52-year-old man on haemodialysis treatment for chronic glomerulonephritis also had a nephrotic syndrome, hypercholesterolaemia, severe arterial hypertension and peripheral vascular disease in stage IIb. He also was a heavy smoker. Following a nonspecific diarrhoeal illness, which caused haemoconcentration, he developed abdominal pain and fever.

Activation of the cryptic DNA binding function of mutant forms of p53.

Wild type p53 assembles into a latent multiprotein complex which can be activated for sequence-specific DNA binding in vitro by proteins targeting the carboxy-terminal domain. Using an optimized system coupling the post-translational modification of wild type p53 to activation of sequence specific DNA binding, we examined the affects of common mutations on the cryptic DNA binding function of p53. Two mutant forms of p53 were shown to be efficiently converted from the latent state by PAb421 and DnaK, but were defective in activation by casein kinase II, indicating that mutant p53 may not be receptive to allosteric regulation by casein kinase II phosphorylation.

Activation of mutant forms of DnaA protein of Escherichia coli by DnaK and GrpE proteins occurs prior to DNA replication.

Mutant forms of DnaA protein, inert in a replication system composed of other purified proteins, are "activated" by DnaK and GrpE heat shock proteins (Hupp, T. R., and Kaguni, J.

Activation of DnaA5 protein by GrpE and DnaK heat shock proteins in initiation of DNA replication in Escherichia coli.

DnaA5 protein, inactive in replication systems dependent on purified enzymes, was activated by addition of a crude enzyme fraction. Based on this assay, two proteins in the crude enzyme fraction were identified that confer replication activity upon DnaA5 protein in a purified enzyme system. That one is DnaK protein was suggested initially from studies in which DnaK protein stimulated another mutant form of DnaA protein in replication assays dependent on a crude enzyme fraction (Hwang, D.