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U Müller

Publications and source records attributed to U Müller.

At least 703 records · Page 39Linked to original sources
PubMedDate not supplied

Application of high resolution two-dimensional polyacrylamide gel electrophoresis of polypeptides from cultured neonatal rat cardiomyocytes: regulation of protein synthesis by catecholamines.

High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was applied to cultured neonatal rat heart muscle cells, incubated for 72 h at 37 degrees C in serum-free medium, either in the absence or in the presence of 0.1 microM norepinephrine. After silver staining, about 340 and 550 protein spots could be seen in cardiomyocytes, cultured either in the absence or presence of norepinephrine. Of these spots, 141 could be further characterized according to isoelectric point and molecular weight, with 71 protein spots being present under both conditions. In cells cultivated in presence of norepinephrine, 58 new protein spots appeared, whereas 12 spots disappeared, and 22 spots increased (whereas 3 spots decreased) in intensity. In comparison with 2-D PAGE of rat cardiomyocytes, the protein pattern of the intact heart of neonatal rats is incongruent. 2-D PAGE of polypeptides of cultured neonatal rat cardiomyocytes may be a suitable tool to study the regulation of protein synthesis by various stimuli with relevance to cardiac growth adaptation, inotropy and heart failure.

Animals↗
PubMedDate not supplied

Regulation of protein biosynthesis in neonatal rat cardiomyocytes by adrenoceptor-stimulation: investigations with high resolution two-dimensional polyacrylamide gel electrophoresis.

The role of alpha- and beta-adrenoceptor-mediated regulation of protein patterns in cultured neonatal rat cardiomyocytes was studied with high resolution two-dimensional polyacrylamide gel electrophoresis. Spontaneously beating neonatal rat cardiomyocytes were cultured for 72 h at 37 degrees C in serum-free medium, supplemented with either the catecholamine norepinephrine (0.1 microM), or with norepinephrine (0.1 microM) plus the alpha 1-adrenoceptor blocker prazosin (1 microM), or with neither of these substances. In transmission light, 105 protein spots could be seen in the lysates from control cells, 244 spots were identified in lysates from norepinephrine-treated cells, and 114 protein species were counted in the case of lysates from cardiomyocytes which had been cultured in the presence of norepinephrine plus prazosin. This experimental approach allows a clear classification of alpha- and non-alpha (probably beta)-adrenoceptor-mediated catecholamine effects on protein synthesis in cardiomyocytes. In comparison with previous experiments (Chang et al., Electrophoresis, this issue, pp. 748-754), less protein species were identified in the untreated control cardiomyocytes, as well as in the norepinephrine treated cells. The only actual modification in the experimental setup in these two series was the addition of dimethyl sulfoxide--a substance known for its repressive effect on oncoprotein expression--to the culture medium, as solvent for prazosin.

Animals↗
PubMedDate not supplied

Mechanisms in acute septic cardiomyopathy: evidence from isolated myocytes.

Although often not considered, the heart is one of the targets of multiple organ failure in sepsis and septic shock, with myocardial depression being a prominent component of this "acute septic cardiomyopathy". Hypotheses concerning the etiology of this depression are increasingly elucidated on a cellular level, including dysfunction of the beta-adrenoceptor/G protein/adenylate cyclase system, calcium channel blockade by cardiodepressant factor, contractile impairment by activated leucocytes, as well as inhibition of protein synthesis by Pseudomonas exotoxin A. In the search for "mechanisms of myocardial depression in sepsis", isolated cardiomyocytes may play a role as research tools with respect to: a) discrimination between direct and indirect cardiodepressant effects; b) identifying not only the acute, but also chronic toxin- and mediator-induced cardiodepression; c) clarification of the mechanism of action of cardiodepressant bacterial toxins and sepsis mediators; d) establishment of in vitro models of leucocyte-mediated cardiodepression in sepsis.

Acute Disease↗
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Promoter inactivation or inhibition by sequence-specific methylation and mechanisms of reactivation.

In studies on adenovirus promoters, predominantly on the late E2A promoter of adenovirus type 2 (Ad2), we have demonstrated by a number of experimental approaches that the sequence-specific methylation of three 5'-CCGG-3' sequences inactivates this promoter. Recently, we have developed a cell-free transcription system in which the methylation-inactivation of eukaryotic promoters can be studied in detail. It has also been shown that methylation-caused promoter inactivation can be reversed by the 289 amino acid E1A protein of Ad2 or of adenovirus type 5. In the presence of this protein with a transactivating effect, transcription is initiated at the authentic cap site of the methylated late E2A promoter. A similar reactivation of the methylated late E2A promoter can also be effected by a cis-acting genetic element, i.e., the strong enhancer of human cytomegalovirus. Further studies will be directed toward the biochemical mechanisms of promoter silencing by sequence-specific methylations.

Adenoviruses, Human↗
PubMedDate not supplied

Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder for which the biochemical defect is as yet unknown. Recently, two cloned segments of human X-chromosome DNA have been described which detect structural alterations within or near the genetic locus responsible for the disorder. Both of these cloned segments were described as tightly linked to the locus and were capable of detecting deletions in the DNA of boys affected with DMD. In an attempt to determine more precisely the occurrence of these deletions within a large population of DMD patients and the accuracy of one of the segments, DXS164 (pERT87), in determining the inheritance of the DMD X chromosome, the subclones 1, 8 and 15 were made available to many investigators throughout the world. Here we describe the combined results of more than 20 research laboratories with respect to the occurrence of deletions at the DXS164 locus in DNA samples isolated from patients with DMD and Becker muscular dystrophy (BMD). The results indicate that the DXS164 locus apparently recombines with DMD 5% of the time, but is probably located between independent sites of mutation which yield DMD. The breakpoints of some deletions are delineated within the DXS164 locus, and it is evident that the deletions at the DMD locus are frequent and extremely large.

Chromosome Deletion↗
PubMedDate not supplied

High frequency of unequal recombination in pseudoautosomal region shown by proviral insertion in transgenic mouse.

The mammalian X and Y chromosomes, in contrast to the autosomes, pair during male meiosis only near the telomeres. Alleles localized in this region can undergo reciprocal exchange during meiosis. Because such sequences do not show strict sex-linked inheritance, they have been termed pseudoautosomal. In man, several DNA sequences have been described which show pseudoautosomal transmission and which are localized in the pairing region at the ends of the short arms of both the X and Y chromosomes (refs 6-9, and D. Page, unpublished results). We now show that the transgenic mouse strain, Mov-15, contains a single Moloney murine leukaemia virus (M-MuLV) genome in its germline, and genetic evidence indicates that the provirus is integrated into the pseudoautosomal region of the sex chromosome. Proviral copies are lost or gained in 7% of male meioses in this strain, and mouse sequences flanking the provirus are tandemly repeated and highly variable. We conclude that unequal recombination events occur with high frequency in the pairing region, possibly because of the presence of repeated sequences.

Animals↗
PubMedDate not supplied

Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex.

Tumour necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) are related proteins, secreted by macrophages and lymphocytes respectively, which play a role in destruction of tumour cells and virally infected cells (for reviews see refs 1,2). TNF-alpha is a non-glycosylated protein of relative molecular mass 17,000 (Mr 17 K), whereas TNF-beta is a glycoprotein of Mr 25 K. Both TNF-alpha and TNF-beta aggregate into multimers and act through the same receptor molecule on target cells. Genes encoding these two TNF proteins have been cloned from mouse and man and in both are closely linked, being separated by approximately 1 kilobase (kb) of DNA. In the mouse these genes are located on chromosome 17, but in man they are on the short arm of chromosome 6. This segment of chromosome 6 also contains the genes of the major histocompatibility complex (MHC), as does chromosome 17 in the mouse. To find out whether the TNF genes are located within the MHC, we used polymorphic restriction sites to analyse a panel of MHC congeneic and intra-MHC recombinant mouse strains. Initially, we mapped the TNF genes the D or Qa region in the distal half of the mouse MHC. We then studied a gene cluster encompassing part of the D and Qa regions and found the TNF genes are located 70 kb proximal to the D gene.

Animals↗
PubMedDate not supplied

MEHMO (mental retardation, epileptic seizures, hypogonadism and -genitalism, microcephaly, obesity), a novel syndrome: assignment of disease locus to xp21.1-p22.13.

A previously unrecognised X-chromosomal mental retardation syndrome is described. Clinical hallmarks are mental retardation, epileptic seizures, hypogonadism, and -genitalism, microcephaly and obesity. Life expectancy of patients is less than two years. Based on the major clinical symptoms this condition is referred to by the acronym MEHMO. Haplotype and two-point linkage analyses in a large three-generation family assign the disease locus to Xp21.1-p22.13, to a region that is flanked by CYBB and DXS365.

Epilepsy↗
PubMedDate not supplied

Integrated physical and transcript map of 5q31.3-qter.

We have constructed a physical and transcript map of 5q31.3-qter. The contig comprises 173 yeast artificial chromosomes (YACs) to which 159 sequence tagged sites (STSs), 47 expressed sequence tags (ESTs), and 32 genes were assigned. Previously published partial YAC contigs of the region have been refined and integrated. Given that the region contains 25 Mbp of DNA the average spacing of markers is approximately 100 kb.

Base Sequence↗
PubMedDate not supplied

[Value of 2-dimensional echocardiography in the diagnosis of infectious endocarditis].

Cross sectional and simultaneous M-mode echocardiograms were performed on 15 consecutive patients with infective endocarditis, 14 of whom had pre-existing cardiac lesions. Patients were divided into two groups based on the presence or absence of echocardiographically detected vegetative lesions. In 10 out of 15 patients vegetations were present (66%): aortic valve 5, mitral valve 1, tricuspid valve 1, both aortic and mitral valves 1 and left ventricular endocardium associated with aortic valve lesion 2. In this group 3 had systemic embolic episodes and 2 died, whereas none of the 5 patients without detectable vegetations had complications. In 6 the preoperative echocardiographic findings could be confirmed at surgery or autopsy. Emergency surgery without catheterization was performed in 2 patients. Two dimensional echocardiography provides an important non invasive method of assessing a significant percentage of vegetations, but a negative echocardiogram does not exclude infective endocarditis. From the present experience and that of others the detection of vegetations by echocardiography identifies a subgroup of patients with a higher risk for complications in whom early operative intervention without catheterization can be performed. Cross sectional echocardiography may also prove helpful for serial examination of valve vegetations.

Adolescent↗
PubMedDate not supplied

[Reactions of the osseous site following implantation of cemented endoprostheses in the femur].

17 autopsy femora with fixed cemented endoprostheses were sectioned horizontally and studied histologically, morphometrically and microradiographically. The implantation period varied between 0 and 12 years. It was frequently found that in distal segments the implant was already loosened shortly after implantation. The morphometrical analyses showed no significant bone changes distal to the trochanter minor. Enhanced microresorption and areas of reduced mineralization were found at the cement-bone interface. The total bone alterations, however, are not very extensive and seem not to be responsible for aseptic loosening, but the frequently inferior fixation instead.

Aged↗
PubMedDate not supplied

[Chronic pain syndromes in orthopedics--typical sites, follow-up and patient characteristics].

This epidemiological questionnaire--study about 362 patients suffering from chronic pain related to muscle skeletal disorders shows the following results: most muscle skeletal pain syndromes are located in the area of the head and back (57.5%), patients who want to be treated in an orthopedic pain ambulance, suffer from at least "moderate" pain according to the verbal rating scale and at least from pain equal or more than 50 according to the numeric rating scale, for most patients (51.9%) the duration of the pain has been between 1 and 10 years, about twice as many women (60.5%) than men (39.5%) suffer from chronic muscle skeletal pain, pain syndromes seem to be of more chronic duration in women than in men, and women tend to take pain killers more frequently than men, most patients with chronic pain consult 2 to 6 doctors, for typical orthopedic pain syndromes most patients consult an orthopedic doctor, patients suffering from chronic headache consult an orthopedic specialist about as frequently as an neurologist or internal specialist.

Adult↗
PubMedDate not supplied

[Catheterized peridural anesthesia as a procedure for intra- and postoperative pain therapy in chemonucleolysis].

In 13 patients scheduled for intradiscal therapy with chymopapain we performed continuous lumbar epidural anaesthesia as a method of intra- and postoperative pain relief. In all patients epidural anaesthesia provided a sufficient analgesia by the use of bupivacaine 0.75% intraoperatively. In contrast to chemonucleolysis under general anaesthesia only half of the patients needed postoperative pain therapy, which was achieved by the epidural injection of bupivacaine 0.25%.

Adult↗
PubMedDate not supplied

Treatment of disseminated malignant melanoma with cisplatin in combination with whole-body hyperthermia and doxorubicin.

Twenty-three patients with disseminated malignant melanoma were entered in a pilot study conducted from January 1983 to January 1988. There were 14 men and nine women. Fifteen patients were available for final evaluation. The criterion for evaluation was the completion of the two thermochemotherapy cycles. Patients received multiple-drug chemotherapy consisting of cisplatin (80 mg/m2, i.v., day 1) and doxorubicin (50 mg/m2, i.v., day 2); applications were repeated on days 22-29. Cisplatin was administered concurrently with whole-body hyperthermia (WBH) on day 1 (body core temperature 41 +/- 0.5 degrees C/h). The following response rates were achieved: complete remission (CR) 0/15; partial remission (PR) 3/15; minor response (MR) 4/15, no change (NC) 3/15; progressive disease (PD) 5/15. These findings are within the range known from the literature of the response to multiple-drug chemotherapy without hyperthermia. Toxicity, in particular renal toxicity, was not enhanced by the combined application of cisplatin and hyperthermia, with the exception of the bone marrow toxicity, which seemed to be slightly more pronounced than that known from normothermic application. Concurrent administration of thermochemotherapy with cisplatin and WBH (41 +/- 0.5 degrees C/h) is no more effective than the multiple-drug chemotherapy without hyperthermia as reported in the literature.

Adult↗
PubMedDate not supplied

[Prenatal serum screening for Down's syndrome].

With the aid of two commercially available analysis programmes we effected non-invasive assessment of the risk for Down's syndrome in 597 pregnancies with healthy fetuses and in 22 pregnancies with trisomie 21-affected fetuses, maternal age ranging between 18 and 45 years. Based on the women's serum levels, hormone concentrations of AFP, free estriol and beta HCG were determined, a multiple of their median was combined with the age factor, and the result used as a parameter for overall risk estimation. A risk cut-off-level greater then 1:250 was considered to represent a positive risk. For patients younger than 35 years test sensitivity, at just over 50%, was found to be low. For those aged 35 years or greater, however, the Dermalog programme was able to detect 94.4% and the Alpha programme 88.2% of fetuses affected by trisomy 21, with a false-positive rate of 19.6 and 19.1%, respectively. If the test were to be applied to all pregnant women beyond 35 years of age the detection rate of Down's syndrome could be nearly doubled compared to today's figure (only 50%, of women in this age group undergo amniocentesis). By the same token the rate of amniocentesis-induced abortion (approx. 1%) could be reduced to about one third.

Adult↗