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Biomedical subjects

R Wolff

Publications and source records attributed to R Wolff.

At least 19 recordsLinked to original sources
PubMed1995

Role for ceramide as an endogenous mediator of Fas-induced cytotoxicity.

Triggering of the Fas/APO-1 cell-surface receptor induces apoptosis through an uncharacterized chain of events. Exposure of Fas-sensitive cells to an agonist monoclonal antibody induced cell death and a 200-300% elevation in endogenous levels of the sphingolipid ceramide, a proposed intracellular mediator of apoptosis. In contrast, similar treatment of Fas-resistant cells caused insignificant changes in ceramide levels. Because resistant cell lines expressed the Fas antigen, these results indicate that these cells have a defect in the proximal signaling events leading to ceramide generation. Exposure of the resistant cell lines to a synthetic analog of ceramide induced apoptosis, thus bypassing Fas resistance and indicating that the signaling pathways downstream of ceramide were intact. Furthermore, activation of protein kinase C with the diacylglycerol analog phorbol 12-myristate 13-acetate significantly reduced Fas-induced cytotoxicity, suggesting opposing roles for ceramide and protein kinase C in regulation of apoptosis. These results provide evidence for ceramide as a necessary and sufficient lipid mediator of Fas-mediated apoptosis and suggest this process may be modulated via activation of additional signal-transduction pathways.

Antigens, Surface↗
PubMed1994

[The child in our society].

Peter Berger once said that children are our "hostages to history", we expect them to ensure continuity. At the same time we project our wishes on them, they are our vectors of the future. Public discourse on children in modern society--charged with historical traditions and diverse expectations--provides a seismographic reading of our hopes and fears as the 20th century draws to a close. Pessimistic attitudes, the sense of looming dangers, appear to be ever more widespread, the discourse about modern childhood takes on an apocalyptic tone, children are seen increasingly as victims or dangerous delinquents. There are complaints that childhood disappeared or would be extended more and more. The paper provides a critical review of present day attitudes to children, investigates the current situation, and discusses the dilemmas that have arisen in the conditions of life and relations between the generations in modern civilization. But a question is also asked: How can we create the conditions that will do children and adults good? Last but not least, what can the health and social services contribute to making childhood worth living?

Child↗
PubMed1993

[Traumatic false aneurysm of the subclavian artery].

Injuries of the subclavian artery are rare; still rarer are aneurysms of the subclavian artery due to blunt or penetrating trauma. Diagnosis can be performed by careful clinical investigation. To identify precisely the nature and site of the injury, angiography and CT are necessary. Rarely associated injuries, such as arteriovenous fistulas, can be recognized by means of these diagnostic tools. This will be of value for planning the surgical approach, which varies with the anatomical site of the injury and the kind of accompanying damage. Subclavian aneurysms should be treated surgically, because embolic or thrombotic complications may threaten the extremity and the brain.

Adolescent↗
PubMed1992

Ocular pharmacokinetics of saperconazole in rabbits. A potential agent against keratomycoses.

The ocular pharmacokinetics of saperconazole, an experimental lipophilic triazole with activity against filamentous fungi, including Aspergillus and Candida species, were evaluated in rabbits by radioassay. The drug was administered by topical, subconjunctival, and oral routes. Following a single 20-microL drop of 0.25% saperconazole in normal corneas, a mean (+/- SEM) peak level of 2.32 +/- 0.06 micrograms/g was achieved in 10 minutes. In débrided corneas, a peak level of 13.09 +/- 2.87 micrograms/g was achieved in 2 minutes. The drug was rapidly cleared from the cornea within 2 hours. The administration of 13 drops during 1 hour resulted in a threefold increase in normal corneal levels and in a sixfold increase in débrided cornea levels. Peak levels following subconjunctival injection in normal corneas (12.91 +/- 2.02 micrograms/g) were approximately twofold greater than those following sustained topical administration (6.19 +/- 0.16 micrograms/g) and, in débrided corneas, were a third higher than those following topical therapy in débrided corneas. Clearance was virtually complete by 8 hours. Levels following oral administration were low and probably subtherapeutic in all ocular tissues that were evaluated. Bioassay studies revealed that 44.17% of the drug in the cornea following topical administration was bioactive.

Administration, Oral↗
PubMed1991

Generation of variability at VNTR loci in human DNA.

Our laboratory has constructed linkage maps of the human chromosomes to use as a tool towards the goal of cloning by position the genes responsible for genetic disorders. Construction of the map required the development of polymorphic marker systems in the form of Restriction Fragment Length Polymorphisms (RFLPs). Work by Yusuke Nakamura in the laboratory led to the identification of more than 200 highly informative Variable Number Tandem Repeat (VNTR) markers. The hypervariable nature of these marker loci has allowed individualization at the DNA level. Techniques for individualization have subsequently been adopted by diverse fields including gene mapping, cancer genetics and forensic biology. These markers have also become a resource to test hypotheses as to how the VNTRs generate their intrinsic variability. We have demonstrated that the hypothesis that VNTRs generate their variability by unequal exchange between homologous chromosomes in incorrect (Wolff et al., 1988; Wolff et al., 1989). Our data are consistent with intrachromosomal models such as unequal sister chromatid exchange and replication slippage. Using DNA derived from nonhuman primate species, we have tested hypotheses that try to explain the sequence relationship at dispersed VNTR loci. Our data reveal that VNTR loci are most likely not related by transposition but rather arose independently at multiple loci.

Alleles↗
PubMed1991

Coronary artery stenting after angioplasty with self-expanding parallel wire metallic stents.

Parallel wire stents were implanted over exchange guide wires at percutaneous transluminal coronary angioplasty sites in 27 canine coronary arteries that were predilated with slightly oversized balloons. Stents were stainless steel, self-expandable, 3.5 to 4.5 mm in diameter, 9 to 12 mm in length, and were made of 10 wires that were longitudinally laser-welded in a zig-zag design. The compressible stent was delivered by the withdrawal of a Teflon outer catheter (4.2 to 4.9F) and the push of a polyethylene inner catheter. Aspirin, 80 mg per day, was given from the day before the study began, and heparin (150 U/kg) was administered during implantation. Quantitative angiography and pathologic examinations were performed at day 0 and at weeks 2, 4, 12, 26 and 52. The coronary angiographic diameter at the stent site immediately after stenting marginally increased from diameter before stenting: 3.22 +/- 0.40 mm versus 3.14 +/- 0.37 mm (p = 0.03), and during a mean of 14 weeks of follow-up, remained unaltered from immediate post-stenting: 3.29 +/- 0.43 mm versus 3.22 +/- 0.40 mm (p = NS) with no stent displacement. Comparisons of patency and thrombosis between heparin-coated and uncoated stents, between left anterior descending and circumflex arteries, and among the three different diameters of stents showed uniformly good results. At microscopy, the wires were oriented perfectly and embedded in the arterial wall, and by 2 weeks they were covered by mucopolysaccharide ground substance, smooth muscle cells, and an almost complete monolayer of neoendothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1991

A map of 22 loci on human chromosome 22.

We constructed a genetic linkage map of the entire long arm of human chromosome 22 with 30 polymorphic markers, defining 22 loci. The map consists of a continuous linkage group 110 cM long, when male and female recombination fractions are combined; average distance between the loci is 5.2 cM. All loci were placed on the map with high support against alternative orders (odds in excess of 1000:1). The order of loci presented in our map is in full agreement with that of the previous linkage maps of chromosome 22 and with the physical assignment of markers. Two markers included in this map, KI-831 (D22S212) and pEFZ31 (D22S32), allowed us to better define the region of the (11;22) translocation breakpoint specific for Ewing sarcoma. Ten additional polymorphic markers were placed on the 22-loci map with odds lower than 1000:1 against alternative locations. In total, we have introduced 29 new markers on the linkage map of chromosome 22.

Chromosome Mapping↗
PubMed1990

Oligonucleotide probes for detection and differentiation of Staphylococcus aureus strains containing genes for enterotoxins A, B, and C and toxic shock syndrome toxin 1.

Different synthetic DNA nucleotide sequences were evaluated as gene probes for the specific detection and differentiation of Staphylococcus aureus strains encoding enterotoxins A (SEA), B (SEB), and C (SEC) and toxic shock syndrome toxin 1 (TSST-1). Identification of sequences unique to each toxin, based on knowledge of their nucleotide sequences, led to preparation of the specific 18-base oligonucleotide probes EA1 (encoding amino acids 177 to 182 of SEA), EB2 (encoding amino acids 105 to 110 of SEB), EC5 (encoding amino acids 125 to 131 of SEC1), and TS1 (encoding amino acids 160 to 166 of TSST-1). In colony blot hybridization analyses, these probes hybridized specifically with DNA from strains that produced the respective toxin serotypes. An excellent (greater than or equal to 93%) correlation between hybridization results (genotype) and toxin protein detection by an enzyme-linked immunosorbent assay (phenotype) was observed in the characterization of both reference and clinical strains of S. aureus for SEA, SEB, and TSST-1. A lower correlation (64%) for SEC reflected a lack of sensitivity in detecting toxin production. Our findings demonstrate that molecular DNA hybridization with synthetic oligonucleotide probes provides another approach for establishing the toxigenicity of S. aureus.

Amino Acid Sequence↗
PubMed1990

[Tuberculous spondylitis--a contribution to the differential diagnosis of space-occupying lesions of the posterior mediastinum].

This report describes a 27-year-old male patient with advanced spondylitis tuberculosa, who, being suspected of having a malignant tumour, was submitted to a CT-guided biopsy. Treatment comprising CT-controlled insertion of a permanent drain, and antituberculous chemotherapy and dorsal stabilisation, was administered. A high-risk intervention (diagnostic and therapeutic thoracotomy with the attendant acute danger of paraplegia was avoided through the use of the most up-to-date imaging procedures available.

Adult↗
PubMed1989

Tolerability of long term clozapine treatment.

Tolerability of long term clozapine treatment (7-8 years) was investigated in 27 female patients (age 34-77 years). Diagnosis according to ICD 9 was schizophrenia in 21 patients, severe psychomotor agitation with mental deficiency in 4 patients and an "endogenous" depression in 2 patients. All patients had previously been treated with different neuroleptics but with inadequate response or distressing side effects. The duration of the disorder was 10-36 years, duration of hospitalisation 10-36 years. At the day of investigation the total dose of clozapine ranged from 52-826 g, the average total dose being 385 g. The daily dose of clozapine ranged from 75 to 600 mg, the average daily dose being 225 mg. Only 2 patients were treated exclusively with clozapine, the other 25 patients were also receiving other neuroleptics. Seventy eight per cent of the investigated patients complained about hypersalivation and 63% showed overweight. In 37% of the patients the EEG demonstrated abnormalities. Mild parkinsonism was reported in 15% and akathisia in 11% of the patients, all these patients being on combined treatment. Clozapine did not induce tardive dysakinesia (TD) in any of the patients within a treatment period of 7-8 years. It is concluded that a potential benefit of clozapine includes a low incidence of neurological side effects even after long term administration.

Adult↗
PubMed1989

One-step extraction of human erythrocyte lipids allowing rapid determination of fatty acid composition.

A one-step extraction procedure to directly quantify cholesterol, phospholipids, and fatty acids in red blood cell membranes has been developed. The method uses a single solvent, isopropanol, which extracts lipids and allows the rapid formation of isopropylic esters of fatty acids by acid catalysis. The efficiency of this new technique has been confirmed by comparing yields of cholesterol and total and individual phospholipids with yields obtained following conventional extraction procedures. Moreover, in comparison to the formation of methyl esters, we demonstrate that directly obtained isopropylic esters immediately allow the quantitative determination of fatty acids, without involving the hydrolytic degradation of fatty acids and the oxidation of unsaturated fatty acids.

Chloroform↗
PubMed1989

Molecular dissection of a contiguous gene syndrome: frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated "island" in the Miller-Dieker chromosome region.

The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be less than 15 kb apart. Three overlapping cosmids spanning greater than 100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region.

Biological Evolution↗
PubMed1989

[Report of experiences with 31 surgically treated patients with deformity of the femur shaft].

In 1986/1987 we made a follow-up of 31 patients having undergone a surgical treatment of a deformity of the femur shaft in 1971 through 1981. For a better interpretation of the results we divided these patients into three partly overlapping groups: Patients with deformities of the angel or rotation, patients being shortened in case of length-differences and those being elongated. Finally we investigated, that in nine out of ten cases we got a good result by correcting angle-and rotation-deformities and by the shortening osteotomy. The extension osteotomy caused more complications and not so good results than those of the first two groups. We recognized, that the follow-up treatment was very long, and the method of the operation was not standardized but was adapted to the circumstances of the single case.

Bone Diseases↗
PubMed1989

[Sarcomas with orofacial localization. A monocentric retrospective study].

It is presented a retrospective study of patient with sarcomas, treated in a hospital of oral surgery in the time of 15 years. The authors give conclusions for the stomatological practice. The exact knowledge of clinical symptoms is important for early diagnosis and treatment, because it is decisive for the prognosis of patients with sarcomas in the orofacial region.

Aged↗
PubMed1988

Leishmania braziliensis panamensis: increased infectivity resulting from heat shock.

Promastigotes of Leishmania braziliensis panamensis were subjected to a heat shock transformation yielding an amastigote-like stage. During the process of conversion, the heat-induced differentiating form displayed an increase in infectivity (as determined by lesion size) accompanied by a total protein composition unlike that of the promastigote and a morphology resembling that of the amastigote. These biological/functional changes may be related to an involvement of a heat shock response in the differentiation of leishmania, thus having important implications in the development of prevention and treatment stratagems.

Animals↗
PubMed1988

[Neurinoma of the L3 spinal nerve root as a cause of stress-induced lumbo-ischialgias].

Degenerative diseases of the lumbar vertebral discs or the vertebral joints are the main causes of low back pain and sciatica following overstraining during sports activities. However, they are rarely seen in sportsmen engaged in competitive sports because these persons are mostly young and well-trained. Other neurological diseases are even rarer as possible causes of sciatica. That is why we report on a young athletic who is a short-distance hurdler (110m hurdle race) and has been suffering from a neurinoma of the spinal nerve root L3 with sciatica and pain in the knee as initial symptoms. Attention is drawn to the importance of neurological examinations as part of medical examinations conducted by sports physicians for the purpose of obtaining an overall guiding picture of the subjects' health status.

Adult↗