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Biomedical subjects

D Wolf

Publications and source records attributed to D Wolf.

At least 163 records · Page 9Linked to original sources
PubMed1985

[Bioavailability and tolerance of xanthinol nicotinate depot preparations. Comparison of a conventional 500 mg xanthinol nicotinate depot tablet with new 500 mg and 1 g depot tablets].

Bioavailability (therapeutic blood levels) and tolerance of two 500-mg xanthinol nicotinate retard tablet forms and one 1-g xanthinol nicotinate retard tablet (Complamin special) were tested in 11 (12) healthy volunteers. Despite the fact that both 500-mg retard tablets had different in vitro release rates the blood levels in man were similar. These results suggest that in vitro release rates of tablets do not predict corresponding blood levels in man. The tablet with a lower release rate also showed a distinctly lower flush rate. In respect to bioavailability and tolerance the 1-g xanthinol nicotinate retard tablet was comparable with corresponding dosages of 500-mg retard tablets. The dosage given was 2 X 500 mg or 1 g xanthinol nicotinate t.i.d. over a period of 10 days each.

Adult↗
PubMed1984

Reconstitution of p53 expression in a nonproducer Ab-MuLV-transformed cell line by transfection of a functional p53 gene.

L12 are Ab-MuLV-transformed cells that express the abl p120 oncogene product but lack the cellularly encoded p53. The functional p53 gene in these cells has been inactivated by the insertion of Moloney virus-like sequences into the first p53 intron. Transfection of L12 cells with a functional p53 gene, contained in a 16 kb Eco RI genomic cloned fragment gave rise to L12-derived cell lines with novel p53 sequences of various sizes and copy number. A high percentage of L12-derived clones efficiently transcribed p53 mRNA and synthesized the p53 protein. Whereas injection of L12 parental cells into syngeneic mice caused the development of local tumors that later regressed, L12-derived clones that expressed p53 caused lethal tumors in syngeneic mice, thus behaving similarly to other Ab-MuLV-transformed p53-producer cell lines. These results suggest that the expression of p53 is essential for tumor cells to exhibit a fully transformed phenotype, manifested in lethal tumors in syngeneic mice.

Abelson murine leukemia virus↗
PubMed1984

Chromosomal assignment of the murine gene encoding the transformation-related protein p53.

p53 is a transformation-related protein that is encoded by the cellular genome and is synthesized at elevated levels in a wide range of different cell line types and in primary tumors of various species. By using several independently established anti-p53 monoclonal antibodies, it was possible to distinguish between p53 of mouse origin and p53 of Chinese hamster origin. By analysis of a series of mouse X Chinese hamster hybrid cell lines containing various mouse chromosomes, we mapped the p53 gene product to mouse chromosome 11.

Animals↗
PubMed1984

Abelson murine leukemia virus-transformed cells that lack p53 protein synthesis express aberrant p53 mRNA species.

Cells of the Abelson murine leukemia virus-transformed line L12 that lack the p53 protein also lack polyadenylated mRNA capable of directing the synthesis of p53 in a cell-free system. Direct analysis of stable polyadenylated mRNA from a variety of cell lines shows that all p53 producers shared a common mRNA species (2.0 kilobases) which hybridized with a p53-specific cDNA probe. This species, which appears to be the mature, normal-sized p53 mRNA, was totally undetectable in L12 cells, which did not produce p53 in vivo. However, L12 cells contained two major p53-specific mRNA species of a substantially larger size (3.5 and 6.5 kilobases) than the p53-specific mRNA in the p53-producing cells. Genomic DNA analysis uncovered an apparent alteration in the 5' proximal part of only one p53 gene, which is unique to the L12 cell line. It is thus possible that the nonproducer phenotype of L12 cells is due at least in part to an alteration within a p53-specific DNA sequence. These findings define a system in which production of p53 appears to be efficiently regulated at the level of stable mRNA and which can be used to study the mechanisms controlling p53 expression in Abelson murine leukemia virus-transformed cells.

Abelson murine leukemia virus↗
PubMed1984

Inactivation of p53 gene expression by an insertion of Moloney murine leukemia virus-like DNA sequences.

Analysis of Abelson murine leukemia virus-transformed L12 cells which lack the p53 cellular encoded tumor antigen revealed alterations in the p53-specific genomic DNA sequences. The active p53 gene, usually contained in a 16-kilobase EcoRI DNA fragment of p53 producer cells, went through major alterations leading to the appearance of a substantially larger 28.0-kilobase p53-specific EcoRI fragment. Detailed restriction enzyme analysis, with genomic probes spanning throughout the whole active p53 gene, indicated that the L12 p53 altered gene contains all the exons and principal introns of the normal p53 16.0-kilobase gene. However, its structure was interrupted by the integration of a novel DNA segment into the noncoding intervening sequences of the first p53 intron. Analysis of the inserted sequences revealed close homology to Moloney murine leukemia virus. This Moloney leukemia murine virus-like particle resides in a 5' to 3' transcriptional orientation, similar to the p53 gene, permitting the transcription of aberrant fused mRNA molecules detected in these cells.

Animals↗
PubMed1984

Positive intradermal tests to D-tubocurarine in patients with cholinergic urticaria.

Patients with cholinergic urticaria exhibit increased hypersensitivity to cholinergic drugs. In the present study, an attempt was made to determine whether these patients would also cross-react to various neuromuscular blocking agents having structures analogous with acetylcholine. The four patients tested showed positive skin tests for D-tubocurarine at concentrations of 1/10,000. None of the 10 subjects in the control group and none of the patients with urticaria had positive responses, not even to a 10-fold higher concentration of D-tubocurarine. These findings suggest that caution should be exercised in the use of neuromuscular blocking agents in patients with cholinergic urticaria.

Adolescent↗
PubMed1984

Nabumetone--a novel anti-inflammatory drug: bioavailability after different dosage regimens.

The bioavailability of nabumetone after different multiple dosing regimens was investigated in healthy male volunteers by determining the main plasma metabolite 6-methoxy-2-naphthylacetic acid. The mean steady state morning plasma level was higher when 1000 mg nabumetone were administered, once daily, at night than after the application of 500 mg twice daily (in the morning and in the evening). There was only a small further increase of the mean steady state morning level when the dose was increased to 1000 mg b.d. In all application regimens the steady state was reached on day 3. The dosage of 1000 mg, once daily, at night with and without a loading dose of 1000 mg in the morning of the first day were compared. When a loading dose was administered the plasma levels rose very quickly to higher values but reached the same mean on day 3 as when given without the loading dose. The half-lives of the terminal beta-phase with mean values of 22.77 h and 22.0 h are of the same order of magnitude as those found in single dose studies. It can be concluded from these results that a dose regimen of 1000 mg once daily, at night would be preferable.

Administration, Oral↗
PubMed1984

Treatment of detrusor instability of the urinary bladder by selective sacral blockade.

Detrusor instability and its associated incontinence frequently impair activity and the results of pharmacological and operative treatment have often been unsatisfactory. Twenty-two patients with idiopathic detrusor instability were treated by selective local anaesthesia of both sacral roots S3. The follow-up period ranged from 4 months to 2 years. In patients with neuropathic detrusor instability, local anaesthesia had no permanent effect, but in four such cases it was possible to achieve continence by permanent blockade of S3 using phenol injections. A disadvantage of the latter procedure was that bladder emptying was achieved only by manual abdominal compression or catheterisation.

Female↗
PubMed1984

[Selective sacral nerve blockade in the treatment of detrusor hyperreflexia of the bladder].

Hyperreflexive detrusor instability causes severe impairment of the patients private and professional life. Involuntary detrusor contractions lead to incontinence. The results of previous pharmacological and operative therapeutic procedures are unsatisfactory. 22 cases with idiopathic hyperreflexive detrusor instability were cured by selective local anaesthesia of both sacral roots S3. The follow-up period ranges from 4 months to 2 years. In case with neurogenic detrusor instability local anaesthesia of the sacral roots S3 has no permanent effect. But in 4 such cases it was possible to reach continence by permanent interruption of the roots S3 using phenolglycerin injections. Unavoidably this success, which enables social rehabilitation, results in voiding disturbance of the bladder which makes voiding by manual bladder compression or even catheterization necessary.

Adult↗
PubMed1983

The presence of p53 transformation-related protein in Ab-MuLV transformed cells is required for their development into lethal tumors in mice.

p53, a cellular-encoded protein, is synthesized at elevated levels in a wide range of tumor cells. Ab-MuLV-transformed cells expressing both the viral-encoded p120 oncogene and the cellular-encoded p53 display a lethal tumor phenotype in syngeneic mice. L12 is an exceptional Ab-MuLV-transformed cell line that expresses the p120 oncogene and lacks the p53 cellular protein. Injection of L12 cells into syngeneic mice is followed by the development of local tumors that are subsequently rejected. Prolonged treatment of L12 cells with TPA, a tumor cell promoter, gave rise to L12T cells that synthesize the p53 protein and exhibit a lethal tumor phenotype. Comparison of one-dimensional proteolytic partial peptide map of p53 obtained from L12T to that obtained from other Ab-MuLV-transformed cell lines confirmed their identity. These results suggest a correlation between the cellular expression of p53 in Ab-MuLV-transformed cells and their capacity to develop into lethal tumors in syngeneic mice.

Abelson murine leukemia virus↗
PubMed1983

Introduction of plasma indomethacin level monitoring and evaluation of an effective threshold level in very low birth weight infants with symptomatic patent ductus arteriosus.

First results are described of individually tailored indomethacin dose rates employing on-line drug level monitoring for pharmacologically induced ductal constriction in very low birth weight infants with symptomatic patent ductus arteriosus (sPDA). In addition prolonged indomethacin therapy was introduced. From our data it appears that the effective threshold indomethacin level for the induction of ductus constriction has to be about 1000 ng/ml 10 h postdosing, while ductus closure can be maintained with a dose rate that exceeds a plasma level of 500 ng/ml for at least 1 week. These maintenance levels were also effective in completely suppressing the urinary metabolite excretion rates of PGI2 and PGE2, which are potential mediators of ductal relaxation. On-line indomethacin level monitoring appears to be practically essential for prolonged indomethacin therapy to overcome the marked variation of indomethacin disposition in preterm infants with sPDA.

Ductus Arteriosus, Patent↗
PubMed1983

Variation in antigenic determinants of p53 transformation-related protein obtained from various species.

p53 is a cellular-encoded transformation-related protein. It is synthesized at elevated levels in tumor cells but has also been detected at low concentrations in several types of nontransformed cells. The p53 of tumor cells is immunogenic and elicits specific antibody production. The antigenic determinants of the p53 protein were studied by specific binding to anti-p53 monoclonal antibodies obtained from the RA3-2C2, PAb122, and PAb421 established hybridoma cell lines, and their conservation was followed in various animal species. We found that whereas mouse p53 efficiently immunoprecipitated with all three anti-p53 monoclonal antibodies, human and rat p53 bound PAb122 and PAb421 but lacked a determinant binding RA3-2C2. The hamster p53 molecule represented a third category, which immunoprecipitated with polyclonal anti-p53 antibodies but failed to bind all three monoclonal antibodies analyzed here. Using these monoclonal antibodies, we detected no variations between p53 found in transformed and p53 found in nontransformed cells, within a given species. The results also showed that RA3-2C2, which recognizes a mouse-specific determinant, binds a site located at a proteolytic digestion fragment of the p53 molecule that differs from that containing PAb122 and PAb421 recognition site(s). p53 is a single protein that can be immunoprecipitated through different antigenic determinants that vary between species.

Animals↗
PubMed1983

Aortic flow velocity curves in the diagnosis and the followup of symptomatic patent ductus arteriosus in preterm infants during therapeutic interventions.

In preterm infants, persistent ductus arteriosus (PDA) fails to close soon after birth and becomes symptomatic (sPDA) in about 40% of the infants, causing cardio-respiratory deterioration by a left-to-right shunt across the PDA. Aortic run-off of blood, predominantly occurring during ventricular diastole, causes an abnormal diastolic retrograde aortic blood flow. This aortic reverse flow can be assessed semi-quantitatively in a noninvasive way, using continuous-wave Doppler-ultrasonography. An increased ratio (R/F ratio) of the abnormal retrograde aortic blood flow (R) related to the normal forward flow (F) in the aorta indicates presence of sPDA in preterm infants. The R/F ratio was assessed in 30 premature infants, including 13 cases without sPDA, and 17 infants with sPDA--in 12 of them before and after surgical ligation of PDA, in five concomitantly to pharmacological closure of PDA by the application of indomethacin. The R/F ratio was low in all infants without sPDA and in infants following surgical ligation of PDA. On the other hand, a high R/F ratio was found in all patients with sPDA before specific treatment. During indomethacin-induced closure of PDA the R/F ratio decreased continuously, whereas it remained high in infants with sPDA not responding to indomethacin treatment.

Aorta, Thoracic↗
PubMed1983

Nabumetone--a novel anti-inflammatory drug: the influence of food, milk, antacids, and analgesics on bioavailability of single oral doses.

The absorption and bioavailability of nabumetone, a novel anti-inflammatory drug, were investigated following administration of single oral doses alone, and with food, milk, antacids, and analgesics to healthy volunteers. Since no unchanged nabumetone has been found in human plasma [Mangan et al. unpublished information], the plasma level of the metabolite 6-methoxy-2-naphthylacetic acid was investigated. After doses of 250, 500, and 1000 mg nabumetone, maximum plasma concentrations of the major metabolite, 6-methoxy-2-naphthylacetic acid, were 9.76, 24.19, and 36.59 micrograms/ml, in nonfasting subjects. The 0-24 h and the 0-72 h areas under the plasma level curves together with the maximum plasma concentration reached, correlated strongly with the dosage level used. When nabumetone was given with food, the areas under the plasma level curve during the first 24 h and the maximum plasma concentrations were found to be significantly increased. No clinically relevant differences of plasma levels were seen when nabumetone was given to male and female subjects. The area under the plasma concentration curve and maximum plasma levels were significantly increased when the drug was given with milk compared to application with water or aluminum hydroxide. No significant differences could be found when the administration of nabumetone with aluminum hydroxide was compared with the administration with water. Co-administration of nabumetone with common analgesics, e.g., acetylsalicylic acid or paracetamol, did not significantly affect the plasma levels or the AUC values of 6-methoxy-2-naphthylacetic acid. The tolerance of nabumetone was found to be excellent in both fasting and nonfasting subjects. No adverse effects could be seen in hematology and clinical chemistry.

Acetaminophen↗
PubMed1983

[Therapeutic problems with indomethacin in preterm infants with persistent ductus arteriosus].

Inhibition of PGE production in eight preterm infants with persistent ductus arteriosus and respiratory distress syndrome was associated with marked improvement in the respiratory and circulatory function in all of them. However, in six of them this effect was only transient. In the posttreatment period of five and a half days reopening of the ductus arteriosus was frequently associated with increased PGE production and a drop of indomethacin serum levels. Three of these six infants were transferred for surgical ligation and the other three infants were successfully treated with a second course of indomethacin. The margin between closure of the ductus arteriosus and the deterioration of kidney function in preterm infants treated with a presently recommended indomethacin dosage is too narrow. Before an improved therapeutic procedure has been developed indomethacin treatment for the closure of persistent ductus arteriosus should not generally be recommended in preterm infants.

Ductus Arteriosus, Patent↗
PubMed1982

Whole bone marrow irradiation for the treatment of multiple myeloma.

Nine patients with multiple myeloma were treated with whole bone marrow irradiation. Six had heavily pretreated disease refractory to chemotherapy. Three had stable disease lightly pretreated by chemotherapy. A modification of the "three and two" total nodal radiation technique was employed. Although varying and often severe treatment related cytopenia occurred, infectious complications, clinical bleeding, and nonhematalogic complications were minimal. Five of nine patients showed a decrease in monoclonal protein components, and one showed an increase during treatment. These preliminary results indicate that a reduction of tumor cell burden may occur in patients following whole bone marrow irradiation and that the technique is feasible. Whole bone marrow irradiation combined with chemotherapy represents a new conceptual therapeutic approach for multiple myeloma.

Adult↗