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Biomedical subjects

C Brunner

Publications and source records attributed to C Brunner.

At least 37 records · Page 2Linked to original sources
PubMed1996

The management of pneumothorax with the thoracic vent versus conventional intercostal tube drainage.

The thoracic vent is a new minimally invasive device for the treatment of spontaneous and iatrogenic pneumothorax. It consists of a polyurethane catheter connected to a plastic chamber containing a one-way valve. As there is no need to connect the thoracic vent to an underwater seal device, immobilization and hospitalization can be avoided. So far the performance of the thoracic vent has been evaluated only in patients without pleural effusions and without signs of tension pneumothorax. Hence, we have performed a randomized study comparing the treatment of pneumothorax by means of the thoracic vent versus conventional intercostal tube drainage in 30 patients, including some with tension pneumothorax. 17 patients were treated with the thoracic vent, 13 with conventional intercostal tube drainage. We found no significant differences in the rate of reexpansion and rate of complications between the group treated with the thoracic vent and the group treated with intercostal tube drainage, but the patients treated with the thoracic vent needed significantly less analgesics. 70% of the patients treated with the thoracic vent were successfully managed on an outpatient basis. All patients treated with intercostal tube drainage were hospitalised; duration of inpatient-therapy was 8 +/- 6.2 days (mean +/- SD).

Adolescent↗
PubMed1995

Determination and regional assignment of grouped sets of microclones in chromosome 1pter-p35.

In an approach to mapping physically the most distal 30 Mb of human chromosome 1p, region-specific clone libraries were generated by microdissection and microcloning. PFGE blot hybridization of single or low-copy microclones against rare-cutter digests of genomic DNA revealed physical linkage for groups of markers. Supplementary PFGE analysis of 31 1p36-p35-specific probes for genetically mapped loci established a total of 15 grouped sets, consisting of altogether 69 markers. Twelve of the grouped sets were located in 1pter-p36.12, as revealed by microcell hybrid mapping; the remaining three were localized proximal to 1p36.12. Regional assignment and ordering of most grouped sets was achieved either by evaluating the included genetic markers or by fluorescence in situ hybridization of representative probes. The genomic extent of individual grouped sets encompassed between 1100 and 2100 kb, covering a total of approximately 22 Mb of the distal chromosome 1p region. One particular grouped set was shown to contain seven polymorphic marker loci that were previously suggested to be distributed across the entire 1pter-p35 region. The increase in the number of hybridization marker probes in 1p36 and their physical mapping is expected to facilitate positional cloning experiments in this region; in particular, the construction of clone contigs may be greatly facilitated.

Blotting, Southern↗
PubMed1995

Identification of two functionally distinct lysine-binding sites in kringle 37 and in kringles 32-36 of human apolipoprotein(a).

The well documented association between high plasma levels of lipoprotein(a) (Lp(a)) and cardiovascular disease might be mediated by the lysine binding of apolipoprotein(a) (apo(a)), the plasminogen-like, multikringle glycoprotein in Lp(a). We employed a mutational analysis to localize the lysine-binding domains within human apo(a). Recombinant apo(a) (r-apo(a)) with 17 plasminogen kringle IV-like domains, one plasminogen kringle V-like domain, and a protease domain or mutants thereof were expressed in the human hepatocarcinoma cell line HepG2. The lysine binding of plasma Lp(a) and r-apo(a) in the culture supernatants of transfected HepG2 cells was analyzed by lysine-Sepharose affinity chromatography. Wild type recombinant Lp(a) (r-Lp(a)) revealed lysine binding in the range observed for human plasma Lp(a). A single accessible lysine binding site in Lp(a) is indicated by a complete loss of lysine binding observed for r-Lp(a) species that contain either a truncated r-apo(a) lacking kringle IV-37, kringle V, and the protease or a point-mutated r-apo(a) with a Trp-4174-->Arg substitution in the putative lysine-binding pocket of kringle IV-37. Evidence is also presented for additional lysine-binding sites within kringles 32-36 of apo(a) that are masked in Lp(a) as indicated by an increased lysine binding for the point mutant (Cys-4057-->Ser), which is unable to assemble into particles. An important role of these lysine-binding site(s) for Lp(a) assembly is suggested by a decreased assembly efficiency for deletion mutants lacking either kringle 32 or kringles 32-35.

Amino Acid Sequence↗
PubMed1995

Sequence polymorphism in kringle IV 37 in linkage disequilibrium with the apolipoprotein (a) size polymorphism.

Apolipoprotein(a) [apo(a)] contains a variable number of identical (K-IV A/B) or nearly identical (K-IV 1, K-IV 30-37) kringle repeats that are homologous to K-IV from plasminogen. The sizes of 414 apo(a) alleles were determined by pulsed-field gel electrophoresis (PFGE) of KpnI-digested DNA. Furthermore, sequence variation in the apo(a) K-IV 30-37 domain was analysed. Reverse transcription/polymerase chain reaction (RT-PCR) cloning of human liver poly A+ RNA followed by sequencing revealed a single nucleotide exchange in the ultimate K-IV (K-IV 37) of apo(a) (codon 4168); this results in an ATG (Met) to ACG (Thr) substitution. A PCR-based restriction assay of genomic DNA demonstrated that this substitution represents a common polymorphism. In 231 unrelated Tyroleans, the frequencies for the K-IV 37 Thr and K-IV 37 Met alleles were 0.66 and 0.34, respectively. The phase between the K-IV 37 Met/Thr and the KpnI size polymorphism was determined for 224 alleles. A significant linkage disequilibrium was detected between the sequence and size polymorphisms of apo(a). K-IV 37 Met was significantly associated with KpnI allele no. 18 (DAB = 0.0267 +/- 0.0101; chi 2 = 10.09, df = 1). The Met/Thr polymorphism was further used to test whether deletions or duplications of K-IV 37 occur frequently in the apo(a) gene. Some 40 apo(a) alleles, 22 of which were from subjects that appeared to be double heterozygotes for K-IV repeat number and the Met/Thr variation were separated by PFGE and analysed for the 4168 Met/Thr polymorphism. The Met and Thr sequences were always present on different size alleles and no evidence for a duplication or deletion of K-IV 37 was obtained. This suggests that the copy number of K-IV 37 is invariable, in contrast to the highly variable K-IV A/B domain of the gene. The 4168 Met/Thr polymorphism had no effect on Lp(a) concentration, neither did it influence the lysine-binding property of the Lp(a) particle.

Adult↗
PubMed1993

Cys4057 of apolipoprotein(a) is essential for lipoprotein(a) assembly.

Lipoprotein(a) contains one copy each of apolipoprotein B-100 and apolipoprotein(a). It has been hypothesized that a disulfide bond might exist between Cys4057 of apolipoprotein(a) and Cys3734 in apolipoprotein B-100. To investigate the role of Cys4057 for lipoprotein(a) assembly, wild-type and in vitro mutagenized apolipoprotein(a) cDNA plasmids were expressed in the human hepatocarcinoma line HepG2. The mutant plasmids encoded apolipoprotein(a) species with Cys4057 exchanged to either serine or glycine. Untransfected HepG2 cells, although able to secrete apolipoprotein B-100-containing lipoproteins, do not synthesize detectable amounts of apolipoprotein(a). After transfection of wild-type plasmid, almost all apolipoprotein(a) in the culture supernatant was present in lipoprotein(a)-like particles as demonstrated by immunoblotting, density-gradient centrifugation, and ELISA. The same analysis performed with supernatants of cells transfected with plasmids mutated in codon 4057 revealed free apolipoprotein(a) glycoprotein without detectable amounts of lipoprotein-associated apolipoprotein(a). Our results strongly suggest the existence of a disulfide bridge between Cys4057 of apolipoprotein(a) and apolipoprotein B-100 within recombinant lipoprotein(a) particles. Furthermore, they indicate that disulfide bridge formation is essential for assembly of the lipoprotein(a)-like complex produced by HepG2 cells and suggest a similar role of Cys4057 during lipoprotein(a) assembly in vivo.

Amino Acid Sequence↗
PubMed1993

Left ventricular diastolic impairment in type 1 diabetic patients with microalbuminuria.

The high incidence of cardiac mortality in type 1 diabetic patients is further increased when diabetic nephropathy is present. Since microalbuminuria (albumin excretion rate > 30 mg/day) represents an incipient stage of diabetic nephropathy, we decided to investigate whether incipient renal changes correlate with early diastolic cardiac dysfunction, known to preceed systolic dysfunction. To test this hypothesis, 13 normotensive type 1 diabetics with incipient nephropathy (mean age 37.8 +/- 3.5, diabetes duration 18.8 +/- 2.6 years), 13 type 1 diabetics without nephropathy (matched for age, diabetes duration and metabolic control) or other microangiopathic changes and 13 normal controls were studied. Diseases known to affect left ventricular performance were ruled out before investigation. Right and left ventricular parameters were assessed by M-mode and Doppler echocardiography. While parameters for left ventricular systolic function stayed within the normal range and did not differ between the two diabetic groups (ejection fraction 69.3 +/- 2.4 vs. 69.6 +/- 1.4%; fractional shortening 40.3 +/- 2.2 vs. 38.5 +/- 1.1%), diastolic function was significantly impaired in diabetic patients with microalbuminuria. This is expressed by an inversed early and late peak flow velocity ratio in patients with microalbuminuria (0.988 +/- 0.04 vs. 1.362 +/- 0.1; p < 0.05) and a significant percentual increase in late (atrial) filling (39.1 +/- 1.7 vs. 29.9 +/- 1.4% when compared to whole filling; p < 0.05) despite a similar rate-corrected isovolumetric relaxation period in both diabetic groups (98.4 +/- 5.8 vs. 95.5 +/- 6.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Lysolecithin actions on vascular smooth muscle cells.

Oxidation of low density lipoprotein increases its atherogenic potential. During oxidation there is an extensive conversion of lecithin to lysolecithin. In rat aortic smooth muscle cells, 2-25 micrograms/ml lysolecithin elevated cytosolic calcium concentration up to 560%. Lysolecithin (10-20 micrograms/ml) increased [3H]thymidine incorporation from 15 cpm/mg cell protein (controls) up to 189 cpm/mg cell protein. Lysolecithin (10 micrograms/ml) potentiated the PDGF-induced (50 ng/ml) [3H]thymidine incorporation up to 6.3 times. The results indicate that lysolecithin could induce mechanisms, by which oxidized low density lipoproteins could promote cell growth and thus contribute to atherosclerosis.

Animals↗
PubMed1991

Mammalian nuclei contain foci which are highly enriched in components of the pre-mRNA splicing machinery.

The organization of the major snRNP particles in mammalian cell nuclei has been analysed by in situ labelling using snRNA-specific antisense probes made of 2'-OMe RNA. U3 snRNA is exclusively detected in the nucleolus while all the spliceosomal snRNAs are found in the nucleoplasm outside of nucleoli. Surprisingly, U2, U4, U5 and U6 snRNAs are predominantly observed in discrete nucleoplasmic foci. U1 snRNA is also present in foci but in addition is detected widely distributed throughout the nucleoplasm. An anti-peptide antibody specific for the non-snRNP splicing factor U2AF reveals it to have a similar distribution to U1 snRNA. Co-localization studies using confocal fluorescence microscopy prove that U2AF is present in the snRNA-containing foci. Antibody staining also shows the foci to contain snRNP-specific proteins and m3G-cap structures. The presence of major components of the nuclear splicing apparatus in foci suggests that these structures may play a role in pre-mRNA processing.

Antisense Elements (Genetics)↗
PubMed1991

The effects of morphology and histopathologic findings on the mobility of the sacroiliac joint.

The sacroiliac joints of seven pelvic specimens were examined to determine functional, morphologic, and histopathologic aspects. The movements were measured in four intact pelvises (from two men and two women). The joint surfaces of all pelvises (from three men and four women) then were examined topographically by means of a photogrammetric method. After this, they were examined histologically to characterize any effects on function. The morphologic investigation revealed sex-specific differences. All joint surfaces from the female pelvises showed circular contours, the centers of which coincided with the iliac tuberosities. These morphologic characteristics were not discernible in the joint surfaces from the male pelvises; these had interlocking irregularities without a topographic pattern. As expected, this configuration involved distinct differences in mobility. Rotation of the sacrum was markedly less in the sacroiliac joints of men than in those of women.

Cadaver↗
PubMed1991

A new behavioral assessment scale for geriatric out- and in-patients: the NOSGER (Nurses' Observation Scale for Geriatric Patients).

Although a great number of psychometric tests and rating scales for the assessment of psychogeriatric patients is available, there is still an urgent need, in research and practice, for a clinical rating instrument that meets the following main requirements: (1) applicable to institutionalized and community patients and covering a wide range of behavioral pathology; (2) acceptable and easy to use for professionals and lay persons alike; (3) covering a wide range of behavior relevant to daily functioning but independent of sex or social status of the individual assessed. The NOSGER contains 30 items of behavior, each rated on a 5-point scale according to frequency of occurrence. Item scores are summarized into 6 Dimension scores (memory, instrumental activities of daily life, self-care, mood, social behavior, and disturbing behavior) which are clinically relevant in dementia, depression, and other psychiatric disorders of old age. Validation studies with a preliminary version of the NOSGER indicated good acceptance of the scale, high inter-rater and test-retest reliability, and high correlations of all NOSGER Dimension scores with results of a variety of established assessment instruments. The NOSGER is currently being used in a number of European and North American centers and should turn out to be a useful instrument for longitudinal studies in psychogeriatrics.

Activities of Daily Living↗
PubMed1991

Intracellular free calcium concentration and thromboxane A2 formation of vascular smooth muscle cells are influenced by fish oil and n-3 eicosapentaenoic acid.

UNLABELLED: The effect of fish oil and n-3 eicosapentaenoic acid (EPA) on intracellular free calcium concentration ([Ca2+]i) and thromboxane B2 (TXB2) formation in resting and stimulated cultured rat vascular smooth muscle cells (VSMC) was examined. In resting control cells [Ca2+]i was 147 +/- 15 nmol l-1 (mean +/- SEM, n = 4). After pretreatment of the cells with fish oil or EPA for 24 days the resting [Ca2+]i was decreased to 126 +/- 10 nmol l-1 and 84 +/- 8 nmol-1, respectively. After stimulation of untreated control cells with either 100 nmol l-1 angiotensin II (AII), 40 micrograms ml-1 low-density lipoprotein (LDL), or 100 ng ml-1 of recombinant platelet-derived growth factor (PDGFAB), [Ca2+]i was (in nmol l-1) 306 +/- 31, 217 +/- 25 and 213 +/- 16. Treatment of cells with fish oil or EPA reduced the stimulatory effect of the agonists, and the following [Ca2+]i values (in nmol l-1) were found: 199 +/- 21, 131 +/- 10, 148 +/- 13; and 175 +/- 11, 98 +/- 12, and 103 +/- 6, respectively. PDGFAB induced a four fold increase in TXB2-generation (270 +/- 28 pg mg-1 cell protein compared with 61 +/- 8.2 pg mg-1 in unstimulated control cells) within 6 min. In cells pretreated with fish oil or EPA, TXB2-formation was reduced by 54% and 44%, respectively. IN CONCLUSION: in rat VSMC stimulated by a variety of vasoactive agonist, fish oil and EPA can markedly attenuate intracellular mechanisms related to changes of cytosolic calcium concentration and eicosanoid production.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1990

Novel cellular activities for low density lipoprotein in vascular smooth muscle cells.

Hyperlipidemia and hypertension play important roles in the pathogenesis of atherosclerosis. To investigate the underlying intracellular mechanisms, we studied the effect of various concentrations of low density lipoprotein from normolipidemic subjects on concentrations of free intracellular calcium, intracellular pH, DNA synthesis, and vascular tone in vascular smooth muscle cells and rings from rat aortas. Low density lipoprotein in the range of 1-15 micrograms/ml induced a dose-dependent increase of concentration of free intracellular calcium and a biphasic change of the intracellular pH. Similar concentrations of low density lipoprotein led to an enhanced DNA synthesis. Furthermore, cumulative addition of 1-15 micrograms/ml low density lipoprotein produced a dose-dependent increase in contractile tension of thoracic aortic rings from rats. The maximal low density lipoprotein-induced contractile response was approximately 70% of that induced by 40 mM KCl. These findings indicate that low concentrations of low density lipoprotein occurring, for example, in the extravascular fluid might contribute to the pathogenesis of cardiovascular diseases by enhancing cell proliferation and vasoconstriction by changing intracellular calcium and intracellular pH.

Animals↗
PubMed1990

[Diagnostic and prognostic elements of non-immunologic feto-placental anasarca. Review of the literature apropos of 7 new cases].

Non immunologic hydrops fetalis (NIHF) is relatively more frequent now since prevention and treatment of blood incompatibilities are common. Seven cases of NIHF were observed between November 1984 and April 1987; antenatal diagnosis by ultrasound scanning was possible in six of these seven cases. Fetal prognosis is usually poor. Only one of the seven children survived, four infants died shortly after birth; two women chose an elective termination of pregnancy at 18 and 23 weeks of gestation, respectively. The review of the literature shows that more than 150 etiologies are associated with this condition. An etiology was found in five of our seven cases, these were all different; renal vein thrombosis, cardiac malformation, cystic hygroma, osteogenesis imperfecta and one case of recurrent NIHF (four affected siblings). Two cases remained idiopathic. Diagnosis of NIHF is best oriented by three investigations: obstetrical ultrasound scanning, fetal echocardiography and any kind of amniocentesis, either for karyotype alone, or to evacuate pleural, pericardial of peritoneal effusions. Ultrasound scanning can evaluate the importance of these effusions and help to choose other etiological investigations. Fetal echocardiography is mandatory because out of the 150 etiologies described in association with NIHF, 25% are cardiac (malformation or dysrhythmias). As already mentioned, fetal prognosis in our series was poor, but perhaps more aggressive in utero treatment could have improve it.

Adult↗
PubMed1990

Fatal encephalitis in a patient with chronic graft-versus-host disease.

A 32-year-old male patient with chronic myelocytic leukemia in accelerated phase received a bone marrow allograft from his 42-year-old HLA/MLC-identical sister. He recovered from acute graft-versus-host disease (GVHD) grade III-IV of skin, liver and gut, but chronic GVHD of progressive onset developed. On day 556 post-graft severe thrombocytopenia was resistant to prednisolone, cyclophosphamide and high dose immunoglobulin. Splenectomy was followed by a normalization of platelet counts. The subsequent clinical course was characterized by progressive muscular atrophy and weight loss. Dysphagia, dysarthria, cachexia and ultimately recurrent pneumonic episodes ensued. The cachectic patient developed a highly abnormal breathing pattern with hypoventilation and intermittent apnea requiring mechanical ventilation. Auditory evoked potentials revealed a considerable dysfunction of the brainstem. The patient died on day 1120 post-graft from pneumonia, aggravated by thoracic muscular insufficiency. Postmortem examination revealed diffuse predominantly lymphoid perivascular infiltration in meninges and CNS tissue; proliferation of activated microglial cells expressing the HLA-DR antigen was prominent in the brainstem. These histologic changes are similar to those observed in the CNS in experimental GVHD. We suggest that this case represents the first documentation of CNS involvement in chronic GVHD.

Adult↗
PubMed1989

Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease.

The intraneuronal accumulation of paired helical filaments in the form of neurofibrillary tangles is one hallmark of the brain pathology in Alzheimer's disease. At certain predilection sites, a small number of similar lesions are also present in the brains of the majority of aged non-demented individuals. As suggested by several studies before, these abnormal cytoskeletal structures contain determinants of microtubule-associated protein tau and ubiquitin. The present study uses a morphological classification of neurofibrillary tangles into different stages of maturation, as suggested by Alzheimer in 1911, and shows by quantitative immunocytochemistry that early stages of neurofibrillary degeneration contain abnormally phosphorylated tau. Immunoreactivity for the altered tau is seen not only in tangles but also in the cytoplasm of some nerve cells lacking neurofibrillary tangles. Similar numbers of such immunoreactive neurons without tangles are present in age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls. In contrast, incorporation of an epitope, recognized by a monoclonal antibody (3-39) raised to paired helical filaments, which is directed against a determinant residing in the 50-65 amino acid residue region of ubiquitin occurs late in the process of tangle maturation and is most pronounced in extracellular 'ghost tangles'. It is suggested that the accumulation of abnormally phosphorylated tau is one of the earliest cytoskeletal changes in the process of tangle formation. Exposure of certain ubiquitin epitopes in the pathological fibers may reflect an unsuccessful attempt of proteolytic degradation.

Adult↗
PubMed1989

Molecular mimicry and Lyme borreliosis: a shared antigenic determinant between Borrelia burgdorferi and human tissue.

The pathogenesis of chronic manifestations in Lyme borreliosis, a disease induced by Borrelia burgdorferi, is at present unresolved. By testing monoclonal antibodies directed against various borrelia antigens, we found an antigenic determinant shared by the 41 kDa flagella protein and human tissue, especially prominent on myelinated fibers of human peripheral nerve, on nerve cells and axons of the central nervous system, as well as on certain epithelial cells (including joint synovia) and on heart muscle cells. Immune reactions against such a shared antigen could play a pathogenetic role in chronic organ manifestations of Lyme borreliosis.

Antibodies, Monoclonal↗