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Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 199 records · Page 11Linked to original sources
PubMed1995

Physiological characterization of a cadmium-resistant mutant in the fission yeast Schizosaccharomyces pombe.

After treatment of the wild-type strain 975 h+ with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) mutants able to grow on YEP-medium containing 15 mM CdCl2 were isolated. Mutant R17 showed a specific resistance to Cd, but no increased tolerance to Pb(NO3)2, CuSO4 or ZnCl2. No higher content of Cd-binding phytochelatins could be detected, but the mutant accumulated lower levels of Cd than the corresponding wild-type. No change, however, was observed in the accumulation of Cu. Under the influence of Cd, the respiratory activity of mutant R 17 is reduced less than in the wild-type. The mechanism of resistance could be an increased secretion or a decreased uptake of Cd.

Cadmium↗
PubMed1995

Acute coronary occlusion secondary to radiofrequency catheter ablation of a left lateral accessory pathway.

A case of asymptomatic acute coronary occlusion secondary to radiofrequency catheter ablation of a left lateral accessory pathway is reported. Due to post-procedural ST modifications of the surface ECG, a coronary angiography was performed which disclosed total occlusion of the first marginal branch of the left circumflex coronary artery. Acute myocardial infarction was confirmed by moderate cardiac enzyme release, abnormal myocardial perfusion scan and mild lateral hypokinesia at echocardiography. This rare but potentially harmful complication of interventional electrophysiology should be kept in mind and coronary angiography performed immediately when coronary occlusion related to radiofrequency application is suspected.

Catheter Ablation↗
PubMed1995

Expression of c-Fos and c-Jun in the cornea, lens, and retina after ultraviolet irradiation of the rat eye and effects of topical antisense oligodeoxynucleotides.

AIMS: Immunohistochemical techniques were used to investigate c-Fos and c-Jun proto-oncogene expression in the cornea, lens, and retina after ultraviolet irradiation of the rat eye. METHODS: Eyes of anaesthetised rats were exposed to 1.5 J/cm2 of ultraviolet radiation (280-380 nm). Animals were perfused 1, 6, or 24 hours after irradiation and tissue sections were incubated with specific antiserum to c-Fos and c-Jun, respectively. RESULTS: Non-irradiated contralateral eyes displayed no c-Fos and c-Jun immunoreactivity. One and 6 hours after ultraviolet exposure numerous c-Fos and c-Jun immunopositive nuclei were observed mainly in the epithelial cell layers of the cornea and the lens epithelium. Scattered labelled nuclei were detectable in the retinal ganglion cell layer and the inner nuclear layer. Twenty four hours after irradiation c-Fos and c-Jun protein expression returned to near control levels. Histological signs of ultraviolet damage (for example, chromatin condensation, nuclear fragmentation) were first recognisable in the corneal epithelium 6 hours after irradiation and became more apparent at later times. CONCLUSION: Thus, the rapid and sustained activation of c-Fos and c-Jun expression in the eye after single ultraviolet exposure may represent the molecular mechanism underlying ultraviolet induced photodamage and initiation of cell death. Furthermore, topical application of a c-fos antisense oligodeoxynucleotide to the ultraviolet exposed rat eye inhibited the increase in c-Fos expression in the cornea, suggesting therapeutic activity of antisense drugs in corneal malignant and infectious diseases.

Administration, Topical↗
PubMed1995

Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma.

Plasma and cerebrospinal fluid (CSF) concentrations of endothelin (ET)-1, ET-3, and big ET-1 in patients with aneurysmal rupture were measured serially for 2 weeks after the onset of aneurysmal subarachnoid hemorrhage (SAH) and compared with levels of ETs in patients without SAH and the plasma concentrations of ETs in normal volunteers. Big ET-1 was the predominant peptide present in the CSF of SAH patients. The CSF concentrations of big ET-1, ET-1, and ET-3 were significantly higher in older patients than in younger patients. In SAH patients with cerebral vasospasm (CVS) documented by transcranial Doppler sonography and clinical signs, postoperative concentrations of ETs in the CSF remained at or were increased above levels measured before surgery. In SAH patients without CVS, the concentrations of ETs in the CSF decreased with time, whereas the time course of CVS coincided with the increase in concentrations of big ET-1 and ET-1. The temporal dependence of concentrations of big ET-1 and ET-1 in SAH patients with and without CVS were significantly different. The volume of hematoma in the basal cisterns as detected by computerized tomography was predictive of the concentrations of ETs in the CSF. Plasma concentrations of ETs were not correlated with CVS. The possible role of ETs in the pathogenesis of CVS associated with SAH and the controversial data reported to date are discussed.

Adolescent↗
PubMed1995

Influence of surface texture and charge on the biocompatibility of endovascular stents.

BACKGROUND: The mechanical behaviour and the surface characteristics of endovascular stents are key factors determining stent patency. In-vitro studies have suggested that surface texture and charge alter the biocompatibility of metallic stents. In this study, the influence of surface texture and charge of metallic stents on thrombosis and neointima formation was evaluated in a rabbit model. METHODS: Twenty-four stainless steel Palmaz-Schatz stents were coated either by an electrochemical deposition of metal on the stent surface or were coated with a metallic film which was implanted into the stent surface by argon ion bombardment. The coatings consisted of platinum, gold, or copper. Coated and uncoated control stents were implanted in rabbit iliac arteries. As antithrombotic therapy, 500 IU heparin and 60 mg aspirin was given intravenously before stent implantation, followed by 60 mg aspirin intravenously every third day for 4 weeks. Thrombus and neointima formation in arterial cross-sections of 24 coated stents were compared with 19 uncoated stents using quantitative, computer-assisted histomorphometry and transmission electron microscopy. RESULTS: A higher stent surface porosity and more surface cracks after stent expansion were found after galvanization than after ion implantation. The in-vitro surface potentials of uncoated steel, copper-, and gold-coated or platinized stents were +150, +120, +180, and +180 mV, respectively. Four weeks after implantation, six of 14 galvanized stents, but none of the uncoated or ion bombarded stents, were occluded by a thrombus. Neointimal hyperplasia was increased in stents coated by galvanization compared with stents coated by ion implantation. In both study groups, the most electropositive coating (platinum or gold) induced markedly less neointima formation than the least electropositive (copper). CONCLUSION: Stent surface texture was the most important factor determining biocompatibility of coated Palmaz-Schatz stents in this study. In contrast to suggestions derived from in-vitro studies, the charge of stents does not seem to play a major role with respect to stent thrombogenicity. Low stent charge correlates with an increased neointima formation.

Animals↗
PubMed1995

Biotin in vitro translation, nonradioactive detection of cell-free synthesized proteins.

In vitro translation of mRNAs into proteins is frequently used to study the coding capacity of RNAs or cDNAs and the functional effects of mutations. In vitro translation assays have traditionally been monitored by following the incorporation of a radiolabeled amino acid into newly synthesized protein. We have optimized an alternative nonradioactive biotin-labeling method. tRNALys is first aminoacylated with lysine, which is then chemically labeled with biotin. When biotin-lysine-tRNALys is added to translation systems, the biotinylated lysine is incorporated into the growing polypeptide chain. After electrophoresis and transfer to a blotting membrane, the biotin-labeled translation products are detected by a chemiluminescent reaction of luminol/iodophenol with streptavidin-coupled horseradish peroxidase. This nonradioactive method yields results equivalent to those obtained using the radioactive method. Biotin-labeled translation products are also biologically functional: (i) biotinylated precursor proteins are transported and processed correctly by dog pancreas microsomes; (ii) transcription factors synthesized by biotin in vitro translation bind specifically to their DNA recognition sequence; and (iii) biotin-modified luciferase keeps its enzymatic activity. The major advantage of the biotin in vitro translation system is that no radioactivity is required, and the method is easy, economical, reproducible and fast--the whole nonradioactive procedure, from translation to detection, can be completed within six hours.

Animals↗
PubMed1995

[Results of follow-up of conservatively and surgically treated injuries of the pelvic ring within the scope of a prospective study].

Follow-up was possible after an average of 23.4 months in 26 cases of pelvic ring injury. These were made up of 7 type A, 8 type B, and 11 type C injuries. Every type A lesion was treated conservatively. External fixation and conservative management were used with type B injuries. Besides conservative treatment both internal and external surgical procedures were applied for correction of type C fractures. While patients treated for type A injuries reported hardly any pain at follow-up, those with types B and C reported dorsal pelvic ring pain of comparable intensity regardless of the treatment given. All patients with a poor outcome following unstable pelvic ring injuries reported dorsal pelvic pain as a principal symptom. Radiological evaluation revealed that the greater the dorsal displacement the more acute the dorsal pain must be expected. An anatomical reduction does not guarantee freedom from pain, however. Besides pain we also rated hip joint flexibility and ability to walk according to the Merle D'Aubigné score. Trauma-related damage and postoperative injuries were distinguished in the neurological evaluation showing a high incidence of lesions of the lateral cutaneous nerve of the thigh following external pelvic fixation. Because of their pelvic injuries 6 patients (23%) were completely or partly disabled and thus unfit for work. The follow-up examinations showed good results in 20 (76%) of the cases. While type B pelvic ring injuries can heal completely when treated by means of a supra-acetabular pelvic fixator, reliable retention cannot be achieved in the case of type C lesions.

Adult↗
PubMed1994

Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86.

In trial ALL-BFM 86, the largest multicenter trial of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight-drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD-cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety-eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

Adolescent↗
PubMed1994

Differential expression of bcl-2 and bax mRNA in axotomized dorsal root ganglia of young and adult rats.

Bcl-2 and Bax have recently been identified as putative repressor and effector proteins respectively, in the cell death program of growth factor-deprived haematopoietic cell lines. Overexpression of bcl-2 in neuronal cell culture prevents apoptosis induced by removal of neurotrophic factors. In the present in vivo study the expression of bcl-2 and bax mRNA has been investigated in dorsal root ganglia of young and adult rats using polymerase chain reaction. A high constitutive expression was observed for both genes in control ganglia. Unilateral transection of the sciatic nerve led to a dramatic decrease in bcl-2 mRNA levels in ganglia of young animals within 5 days following nerve lesion and a partial recovery thereafter. In contrast, the decline in bcl-2 mRNA was much less pronounced in axotomized ganglia of adults. The amount of bax transcripts did not change significantly in ganglia of both young and adult rats up to 20 days after nerve injury. The decrease in bcl-2 expression in dorsal root ganglia may be part of the molecular mechanism leading to neuronal cell death after axotomy-induced deprivation of neurotrophic factors. The age-dependent decline in the ratio of bcl-2 to bax gene products may explain the greater susceptibility of immature neurons to apoptosis.

Animals↗
PubMed1994

[Atrial fibrillation: anticoagulants or not?].

Atrial fibrillation is a common arrhythmia, and the risk of embolic stroke in patients with nonrheumatic atrial fibrillation is increased about fivefold. Until recently, there has been no consensus on the use of anticoagulants in patients with nonrheumatic atrial fibrillation, and the role of aspirin has been controversial. Since 1989, 5 randomized, controlled trials have been published comparing warfarin or aspirin with placebo for primary prevention of stroke in patients with nonrheumatic atrial fibrillation. All these trials have shown a clear benefit of anticoagulant therapy (risk reduction 35 to 86%), whereas the benefit of aspirin has been less obvious (risk reduction 15 to 42%). In all these studies, anticoagulation level was moderate (INR 1.5 to 3.0), and the rate of major bleeding was reported to be low (0.8 to 2.5% per year). Anticoagulant therapy does not seem to be warranted in patients < 60 years old with lone atrial fibrillation, and the decision should be individualized in patients > 75 years old in whom the risk of major bleeding is high. In these situations, aspirin (325 mg per day) appears to be a safe and reasonable alternative.

Aged↗
PubMed1994

Time-resolved flow cytometry for the measurement of lanthanide chelate fluorescence: II. Instrument design and experimental results.

A time-resolved flow cytometer capable of measuring a luminescence with a decay time in the range of 10 microseconds to 2 ms, typical for some lanthanide chelates, is presented. The instrument permits acquisition of conventional light scatter and prompt fluorescence signals as well as detection of slowly decaying luminescence by a photon counting unit for a selectable time period of 1 microsecond to 1 ms. During photon counting, the laser beam is turned off by an acoustooptic deflector. The design of a flow chamber with an average geometrical light collection efficiency of 35% over a distance of 1.7 mm is presented and analyzed by ray tracing. A pulse processing system featuring digital integration of the conventional signals and a transputer system for the acquisition and the transfer of the measured parameter values to a host computer is described. Instrument function is verified with lyophilized human lymphocytes stained for the CD8 antigen with dye-loaded liposomes. Quantitation of cell-associated europium chelate fluorescence, displaying a decay time of 1.6 ms, is demonstrated. Elimination of fast decaying background emission generated by DNA-associated ethidium bromide is shown. The background generated by instrument components in the time-gated measurement channel is characterized, and measures for its complete elimination are discussed.

Chelating Agents↗
PubMed1994

Inhibition of c-Fos protein expression in rat spinal cord by antisense oligodeoxynucleotide superfusion.

Peripheral noxious stimulation leads to a rapid and transient expression of c-fos, c-jun and other immediate-early genes (IEGs) in the spinal cord. However, the role of IEG encoded transcription factors in plasticity of spinal neurons remains speculative. In the present study we have shown that superfusion of rat spinal cord with antisense oligodeoxynucleotides complementary to c-fos mRNA suppresses heat-induced c-Fos protein expression without affecting other members of the Fos and Jun family, thus providing a technique to determine the function of IEGs in vivo.

Animals↗
PubMed1994

The membrane proteins TRAMp and sec61 alpha p may be involved in post-translational transport of presecretory proteins into mammalian microsomes.

The presecretory protein ppcecDHFR, a hybrid between preprocecropinA and dihydrofolate reductase, is transported into mammalian microsomes post-translationally, i.e. independent of ribosome and signal recognition particle. Here, the involvement of microsomal proteins in ribonucleoparticle-independent transport of ppcecDHFR was analyzed by transport into trypsin-pretreated microsomes and by transport of a truncated version of ppcecDHFR and subsequent chemical cross-linking. We observed that post-translational transport of ppcecDHFR can occur into microsomes which had been pretreated with trypsin (final concentration, 100 micrograms/ml) and that of the known transport components only TRAMp and sec61 alpha p are still present under these conditions. Furthermore, we found that the truncated ppcecDHFR, ppcecDHFR-98mer', can be cross-linked to 36 kDa microsomal membrane proteins during post-translational transport. Therefore, the two microsomal membrane proteins with molecular masses of about 36 kDa, TRAMp and sec61 alpha p, appear to be involved in the post-translational transport of ppcecDHFR and ppcecDHFR-98mer.

Adenosine Triphosphate↗
PubMed1994

A stably folded presecretory protein associates with and upon unfolding translocates across the membrane of mammalian microsomes.

The presecretory protein ppcecDHFR, a hybrid between preprocecropin A and dihydrofolate reductase, is transported into mammalian microsomes post-translationally, i.e. independently of ribosome and signal recognition particle. Upon staging the transport process, stably folded ppcecDHFR bound to mammalian microsomes and subsequently translocated across the membrane. Membrane association depended on the signal peptide but involved neither ATP nor an N-ethylmaleimide-sensitive microsomal protein. Membrane insertion of bound ppcecDHFR did not necessitate unfolding of the DHFR domain but depended on ATP and an N-ethylmaleimide-sensitive microsomal protein. Completion of translocation relied on unfolding of the DHFR domain. Thus mammalian microsomes have the capability of transporting a bound and folded precursor protein, i.e. to trigger unfolding of a precursor protein on the membrane surface.

Adenosine Triphosphate↗
PubMed1994

Efficacy of rapid atrial pacing for conversion of atrial flutter in medically treated patients.

To determine factors affecting the success rate of rapid atrial pacing in converting atrial flutter to sinus rhythm in medically treated patients, we prospectively used this technique for 120 consecutive episodes in a total of 110 patients (94 male, 16 female, mean age 63 +/- 14 years). Structural heart disease was present in 77%, and all patients were receiving antiarrhythmic drugs at the time of the procedure. Atrial flutter type I was present in 92 of 110 patients (84%), and atrial flutter type II in 18 of 110 (16%). Primary success rate (return to sinus rhythm either immediately or after < 10 min of atrial fibrillation) was 70% (71/102) for flutter type I, and 6% (1/18) for flutter type II (p < 0.001). Delayed success (conversion to sinus rhythm in > 10 min but < 24 h) was observed in 15 additional episodes of flutter type I (15%) and in 1 additional episode of flutter type II (6%). The only clinical factors predicting primary success were (a) characteristics of flutter waves on the 12-lead surface electrocardiogram, (b) duration of flutter (primary success rate of 81% if flutter < 1 month vs. 57% if > 1 month, p < 0.05), and (c) flutter rate (primary success rate of 78% if < 260/min vs. 56% if > 260/min, p < 0.05). In 6/71 episodes of flutter type I (8%), prolonged sinus pauses or severe bradyarrhythmias occurred after conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

NADH: ubiquinone oxidoreductase in obligate aerobic yeasts.

The strictly aerobic yeasts Candida pinus, Cryptococcus albidus, Rhodotorula minuta, Rhodotorula mucilaginosa and Trichosporon beigelii possess mitochondrial NADH dehydrogenases with significant features of the NADH:ubiquinone oxidoreductase (complex I). These species show in all growth phases and under standard cultivation conditions, NADH dehydrogenases of approximately 700 kDa, which are sensitive to rotenone, a specific inhibitor of this complex. Identical results were obtained with the weakly fermenting C. pinus. The facultatively fermenting yeasts Saccharomyces cerevisiae and Kluyveromyces marxianus do not possess the 700 kDa-complex and are insensitive to rotenone. In S. cerevisiae, a rotenone-insensitive NADH dehydrogenase of about 500-600 kDa is detected only in stationary phase cells. As in Neurospora crassa, upon incubation of the obligately aerobic yeast R. mucilaginosa with chloramphenicol, an intermediate NADH dehydrogenase of approximately 350 kDa was formed, which was insensitive to rotenone.

Aerobiosis↗
PubMed1994

Induction of c-Jun and suppression of CREB transcription factor proteins in axotomized neurons of substantia nigra and covariation with tyrosine hydroxylase.

In adult rats, the expression of transcription factor proteins c-Jun and CREB and their colocalization with tyrosine hydroxylase (TH) were investigated in neurons of the substantia nigra compacta (SNC) axotomized by stereotaxic unilateral transection of the medial forebrain bundle (MFB). Axotomized SNC neurons were identified by injection of the retrograde tracer horseradish-peroxidase-coupled-gold (HRP-gold) into the ipsilateral striatum 5 days prior to MFB transection. Nuclear c-Jun immunoreactivity (IR) appeared 36 h after MFB transection in SNC neurons, was maximal after 5 days, and declined after 10 days. c-Jun-IR was visible in HRP-gold-labeled SNC neurons, demonstrating that c-Jun is in fact expressed in axotomized neurons. The constitutively expressed CREB (calcium/cAMP response element-binding protein, syn. CREB-1) was present in apparently all neuronal and glial cells in the brains of untreated rats including those SNC neurons that coexpressed TH. Three days following MFB transection, the nuclear CREB-IR disappeared in the axotomized SNC neurons labeled by TH-IR and was almost completely absent after 20 days in this neuronal population. The TH-IR rapidly declined 5 days after MFB transection, and 10 and 100 days post-axotomy the number of TH-labeled neurons was reduced by 52 and 80%, respectively. During this period, the majority of surviving TH positive neurons coexpressed c-Jun but were immunonegative for CREB. Between 3 and 60 days following MFB transection, the number of CREB-labeled glial cell nuclei increased in the ipsilateral substantia nigra by about 80%. Concomitantly, expression of GFAP, a marker protein for astrocytes, was also enhanced whereas nuclear c-Jun-, JunD-, and c-Fos-IR did not change in glial cells. These findings demonstrate that c-Jun can be expressed in axotomized neurons during the absence of CREB and suggest a role of c-Jun in the transcriptional control of the TH gene.

Animals↗