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Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 253 records · Page 14Linked to original sources

Expression of the junD proto-oncogene in the rat spinal cord and skin following noxious cutaneous ultraviolet irradiation.

Noxious peripheral stimulation induces the expression of various proto-oncogenes in rat spinal neurons. However, proto-oncogene expression seems to differ depending on the mode of the stimulus. Here, we report that noxious cutaneous ultraviolet (UV) irradiation results in a nearly 8-fold increase in junD mRNA levels in the rat lumbar spinal cord. RNA slot-blotting and hybridization techniques revealed a transcriptional activation of the junD proto-oncogene after 6 h, but not 1 h following UV exposure. These results suggest that low-frequency ongoing afferent impulse discharge is reflected by an accumulation in junD transcripts.

Afferent Pathways↗

Genetic diversity of the yeast Candida utilis.

The electrophoretic karyotypes and some mtDNA restriction fragment patterns of 13 strains of Candida utilis and one strain of Hansenula jadinii were compared. PFGE separations revealed remarkable chromosome length polymorphisms between two groups of strains suggesting that perhaps they do not belong to the same species. However, all strains had the same or similar EcoRI, HindIII and BamHI mtDNA restriction patterns. The mtDNA genomes had an average size range of 55 kb. These results support the supposition that C. utilis is a yeast with a highly variable electrophoretic karyotype as already known for another imperfect yeast species, Candida albicans.

Candida↗

The transcription factors c-JUN, JUN D and CREB, but not FOS and KROX-24, are differentially regulated in axotomized neurons following transection of rat sciatic nerve.

In adult rats, expression of c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24 and CREB proteins was investigated by immunocytochemistry in L4 and L5 dorsal root ganglia and lumbar spinal cord for up to 300 days following transection of the left sciatic nerve. In dorsal root ganglia, expressions of c-JUN and JUN D were increased 10 h and 15 h after sciatic nerve transection, respectively. c-JUN was still at an elevated level after 300 days predominantly in small diameter neurons, whereas JUN D had declined to control levels after 100 days. In contrast to the JUN proteins, expression of CREB showed a delayed onset after 10 days and reached a maximum between 70 and 150 days. In motoneurons, expression of c-JUN and JUN D was increased 15 h and 25 h after sciatic nerve transection, respectively. Expression of c-JUN remained increased after 150 days, whereas JUN D had declined to control levels after 70 days. In contrast, expression of CREB declined within 30 h in axotomized motoneurons and remained on a reduced level for up to 150 days. JUN B, c-FOS, FOS B and KROX-24 were not induced either following axotomy or following a repeated nerve crush. Sciatic nerve transection including the surgical procedure transynaptically provoked a transient expression of all JUN, FOS and KROX-24 proteins in neurons of spinal dorsal horn which disappeared after 5 days except the expression of JUN D which lasted for up to 20 days. In contrast, CREB immunoreactivity was not at all altered in neurons of spinal dorsal horn. In untreated animals, CREB and to a lesser extent JUN D showed an ubiquitous expression in neurons and glia cells of spinal cord, whereas expression of c-JUN and a weak expression of FOS B were restricted to motoneurons. In neurons of the dorsal root ganglia, a basal expression was found for c-JUN, JUN D and CREB and, at a low level, for FOS B and KROX-24. c-JUN and JUN D were colocalized with CREB in many cells such as interneurons, motoneurons, dorsal root ganglion cells and glial cells indicating the possibility for both the control of c-jun and jun D expression by CREB and the competition of JUN and CREB proteins for CRE consensus sequences.

Animals↗

Potentiated expression of FOS protein in the rat spinal cord following bilateral noxious cutaneous stimulation.

A noxious mechanical or chemical stimulus to the ventral skin of one hindpaw induced the expression of FOS proteins ipsilaterally in the spinal dorsal horn neurons in the rat. The number of FOS-labelled cells reached a maximum at 2-3 h, and decayed to basal levels within 6 h after the stimulus. When a first noxious stimulus was applied to the contralateral hindpaw 1-1.5 h prior to this stimulus, the number of FOS-labelled cells increased, over all laminae, to 153% (mechanical) and 164% (chemical) compared to the number produced by a single stimulus. This effect of a prior stimulus in increasing the number of FOS-labelled cells produced by a contralateral stimulus persisted for several hours after the first stimulus. The results are interpreted as a sensitization of dorsal horn neurons induced by peripheral noxious stimuli, which is manifest at the molecular biological level.

Animals↗

Significance of ventricular late potentials in non-ischaemic dilated cardiomyopathy.

To assess the incidence and clinical significance of ventricular late potentials in non-ischaemic dilated cardiomyopathy, 51 consecutive (44 male, seven female, mean age 53 +/- 11 years) patients with dilated cardiomyopathy were studied. Twenty-eight patients (55%) were in New York Heart Association functional class III or IV, 34 out of 51 (76%) had a left ventricular ejection fraction of less than 40%, 10 out of 51 (20%) had a history of sustained ventricular tachycardia (VT), 24 out of 37 (65%) had runs of non-sustained ventricular tachycardia during Holter monitoring and 15 out of 51 (29%) had a left bundle branch block. A signal-averaged electrocardiogram (gain 10(6) x, bipolar chest leads, filters 100-300 Hz) was performed in all the patients; late potentials were considered present if the total filtered QRS duration was longer than 118 ms and the interval between the end of QRS and the voltage 40 microV was more than 40 ms in the absence of left bundle branch block (total filtered QRS duration greater than 140 ms and interval between the end of QRS and the voltage 40 microV greater than 50 ms in the presence of left bundle branch block). Ventricular late potentials were detected in 22 out of 51 patients (43%). Late potentials were present in 80% (eight out of 10) of patients with sustained ventricular tachycardia but in only 34% (14 of 41) without sustained ventricular tachycardia (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Late ventricular potentials and myocardial infarction. A critical analysis].

The identification of patients at high risk of developing severe ventricular arrhythmias or sudden death after acute myocardial infarction is one of the major preoccupations of cardiologists. In this field, electrocardiographic signal averaging represents a promising technique and the prognostic value of late potentials in the post-infarction period has been well demonstrated during the last 10 years. However, in order to use optimally the information obtained by this technique the limitations should be understood: what do late ventricular potentials represent from the electrophysiological point of view? Do they play an active role in the genesis of ventricular arrhythmias or are they only a marker? What is the best method of recording late potentials? What are the criteria of normality of signal averaged recordings? What is the predictive value of late potentials in the post-infarction period? At what moment should they be searched for? Are they affected by medical therapy? These are some of the questions which have not yet been answered and which are addressed in this article.

Action Potentials↗

In vitro activity of taurolidine, chlorophenol-camphor-menthol and chlorhexidine against oral pathogenic microorganisms.

The antimicrobial activity of taurolidine (Taurolin, CAS 19388-87-5), a synthetic broad-spectrum antimicrobial agent and anti-toxin, and two conventional antiseptics, chlorophenol-camphor-menthol (CCM) and chlorhexidine digluconate (CHX) were compared using the serial dilution test on 10 potential oral pathogenic bacterial species. The minimum inhibitory and minimum bactericidal concentrations were lowest for CHX (MIC 0.03-0.12 mg/ml), followed by taurolidine (MIC 0.12-0.5 mg/ml) and CCM (MIC 0.5-2.0 mg/ml). However, if both bacterial efficacy and cytotoxicity are considered, only taurolidine achieves extensive bactericidal activity with tissue tolerability.

Anti-Infective Agents, Local↗

[The therapy of the postextraction syndrome with Taurolin. A controlled clinical study].

In a controlled clinical study with a total of 200 patients the broad spectrum agent and antitoxin taurolidine (Taurolin) was clearly superior to conventional medication with the broad spectrum antibiotic chlortetracycline (Aureomycin) when applied topically to treat the postextraction syndrome. Thus, the mean duration of therapy (primary target criterion) with Taurolin (group A) was 5.6 days compared to 8.2 days with the standard therapy (group B). In statistical terms this difference was highly significant (p < 0.0001). Compared with the conventionally treated patient group, the clinical control parameters such as pain, swelling, secretion, tenderness to pressure and remission (secondary target criteria) in the Taurolin group exhibited not only a markedly more rapid normalisation of the score-data during the initial phase, but also an appreciably shorter interval until the patients were symptom-free. Age, gender, localisation of the lesion or facultative systemic antibiotic or analgetic administration had no demonstrable effect on the course of the treatment, although the patients in the reference group required concomitant medication with antibiotics (p = 0.007) and analgetics (p = 0.01) considerably more often than those in the Taurolin group.

Adult↗

Pain: a kaleidoscope of ideas, concepts and approaches.

The following pages contain summaries and short statements on chronic pain providing further material for reflection and debate, namely: a) synopses of recent findings on: the physiology and biochemistry of pain; the contribution of psychoneuroimmunology; b) some views on a sociology of pain; c) analysis of various concepts and approaches which consider pain as: a symptom of disease a form of behaviour a psychosomatic reaction and a social learning process a communication phenomenon a symptom of disintegrated life a disruption in the integrity of the system a signal of broken unity a breach in the wholeness of the individual; d) a holistic approach in pain therapy; e) some unanswered questions.

Chronic Disease↗

[Idiopathic sustained ventricular tachycardia in the young adult with right bundle-branch and left axis deviation].

The authors report 4 cases of sustained ventricular tachycardia with right bundle branch block and left axis deviation morphology. These ventricular tachycardias which are usually sensitive to Verapamil are often mistaken for supraventricular tachycardia. However, they are a specific clinical, electrocardiographic and electrophysiological entity. The origin of the tachycardia is probably in the Purkinje fibres of the left posterior hemibranch of the His bundle. The mechanism is controversial: much evidence points to reentrant phenomenon, but, in the present state of our knowledge, triggered activity cannot be formally excluded.

Action Potentials↗

Sequential expression of JUN B, JUN D and FOS B proteins in rat spinal neurons: cascade of transcriptional operations during nociception.

Expression of the immediate-early gene encoded proteins JUN B, JUN D and FOS B was investigated by immunocytochemistry in rat L5 spinal cord up to 24 h following stimulation of hind limb somatosensory nociceptors by noxious heat or injection of formalin. In both experimental protocols, JUN B, which did not show basal expression, reached maximum expression after 2 h and thereafter slowly decreased. In contrast, the expression of JUN D, which was present before stimulation in many spinal neurons, was increased after 4 h, reached its maximum after 8 h and thereafter remained elevated. FOS B which was absent under basal conditions reached its maximum between 4 h and 8 h and thereafter declined but was still present after 24 h. All immunoreactivities were restricted to the ipsilateral dorsal horn except JUN D which was also induced in the contralateral side after 8 h. The results are discussed in respect to their meaning for transcriptional operations of JUN and FOS proteins.

Animals↗

Photoaffinity labeling of dog pancreas microsomes with 8-azido-ATP inhibits association of nascent preprolactin with the signal sequence receptor complex.

Transport of bovine preprolactin into dog pancreas microsomes involves a microsomal protein which is sensitive to photoaffinity labeling with azido-ATP and which is distinct from the ATP-binding protein, immunoglobulin heavy chain binding protein. Here we addressed the question of what stage of preprolactin transport is affected. Thus a nascent presecretory protein which is related to preprolactin, termed ppl-86mer, was employed. Here we show that the nascent preprolactin did not become associated with the alpha-subunit of the signal sequence receptor complex after photoaffinity labeling of microsomes with azido-ATP. Therefore, we conclude that the microsomal protein which is sensitive to photoaffinity labeling with azido-ATP acts prior to the signal sequence receptor complex.

Adenosine Triphosphate↗

Ventricular late potentials and induced ventricular arrhythmias after surgical repair of tetralogy of Fallot.

Ventricular tachycardia (VT) and sudden death are rare but recognized complications after surgical repair of tetralogy of Fallot. We prospectively studied 31 patients (19 boys and 12 girls, mean age +/- standard deviation 7 +/- 4 years) with postoperative tetralogy of Fallot, by means of right-sided cardiac catheterization, 24-hour Holter monitoring, body-surface and intracavitary signal-averaging (gain 10(5) to 10(6), filters of 100 and 300 Hz) and programmed ventricular stimulation (1 and 2 extrastimuli, 3 basic cycle lengths, right ventricular apex and outflow tract). All patients were asymptomatic and none had documented or suspected ventricular arrhythmias. Ventricular late potentials were detected in 10 of 31 patients (32%) and spontaneous ventricular arrhythmias in 12 of 31 patients (39%). No sustained VT was induced by programmed ventricular stimulation but nonsustained VT was induced in 3 patients (10%). Patients with inducible VT more often had late potentials (3 of 3 vs 7 of 28, p less than 0.01), and spontaneous ventricular premature complexes (VPCs) during Holter monitoring (3 of 3 vs 9 of 28, p less than 0.05). To predict VT inducibility, late potentials had a sensitivity of 100%, a specificity of 75%, a positive predictive value of 30% and a negative predictive value of 100%. For spontaneous VPCs, the figures were 100, 68, 25 and 100%, respectively. It is concluded that shortly after repair of tetralogy of Fallot, the presence of both spontaneous VPCs and ventricular late potentials are associated with an increased incidence of inducible VT. Conversely, the absence of VPCs and ventricular late potentials may identify patients at low risk of subsequent ventricular arrhythmias.

Adolescent↗

Regulation of calcitonin gene-related peptide mRNA expression in the hearts of spontaneously hypertensive rats by testosterone.

Previous studies have demonstrated the existence of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibres and nerve cell bodies in the rat heart. Using polymerase chain reaction we have investigated whether CGRP messenger RNA (mRNA) could be detected in heart tissue of spontaneously hypertensive rats, and whether CGRP-mRNA levels are affected by gonadectomy and testosterone substitution. Two weeks after castration CGRP-mRNA levels decreased to 65.2 +/- 6.4% of control values, whereas daily dihydrotestosterone substitution reversed this effect (88.0 +/- 1.2% of control). Our results indicate that steroid hormones control the expression of intracardiac CGRP on a pretranslational level.

Animals↗

Reduction in the frequency of ventricular late potentials after acute myocardial infarction by early thrombolytic therapy.

Ventricular late potentials are strong predictors of arrhythmic events after acute myocardial infarction (AMI). To assess the effect of intravenous thrombolysis on the incidence of ventricular late potentials, 223 consecutive patients surviving a first AMI were included in the present study: 59 patients (53 men, 6 women, mean age +/- standard deviation 55 +/- 10 years) received intravenous recombinant tissue-type plasminogen activator (100 mg over 3 hours, group A) and 164 patients (123 men, 41 women, mean age 61 +/- 11 years) received conventional medical treatment (group B). A time-domain signal-averaged electrocardiogram and a high-resolution beat-to-beat recording (gain 10(6), filters 100 to 300 Hz) were performed at 10 +/- 3 days after AMI. There was no difference between group A and B patients in terms of AMI location (anterior in 28 of 59 vs 80 of 164, difference not significant [NS]), mean left ventricular ejection fraction (55 +/- 10 vs 55 +/- 13%, NS), or presence of heart failure (New York Heart Association class III or IV in 12 of 59 vs 40 of 164, NS). The incidence of ventricular late potentials was 10% (6 of 59) in group A and 24% (39 of 164) in group B (p less than 0.05). Among the 146 patients who underwent coronary arteriography, the incidence of ventricular late potentials was 13% (10 of 80) in patients with a patent infarct-related artery and 26% (17 of 66) in patients with an occluded infarct-related artery (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Ultraviolet irradiation of the skin attenuates calcitonin gene-related peptide mRNA expression in rat dorsal root ganglion cells.

Calcitonin gene-related peptide (CGRP) mRNA expression in rat dorsal root ganglion cells was measured by polymerase chain reaction after ultraviolet (UV) irradiation of the skin. The aim was to investigate whether a noninvasive peripheral lesion set by UV irradiation influences neuropeptide gene expression thus possibly contributing to the pathophysiology of the UV erythema. Forty-eight hours after irradiation, when the inflammatory response of the skin was at its maximum, there was a decrease in CGRP mRNA levels to 50% of the control values. The results demonstrate that exposure of the peripheral receptive field to noxious UV radiation affects neuropeptide gene expression in primary sensory neurons.

Animals↗

Development of monoclonal antibodies against different protein and carbohydrate epitopes of dipeptidyl peptidase IV from rat liver plasma membranes.

Dipeptidyl peptidase IV (DPP IV) is a serine exopeptidase expressed at high levels in rat kidney, liver and lung. We established eight monoclonal antibodies against partially purified DPP IV from rat liver plasma membranes. By means of a competitive dot blot assay with purified DPP IV, these antibodies were shown to recognize four different epitopes of the glycoprotein, designated A - D. The epitopes are located on the extracellular domain of DPP IV, as shown by papain digestion of liver plasma membranes. Treatment of DPP IV with neuraminidase and glycopeptide N-glycosidase F, as well as incubation of hepatocytes with the alpha-mannosidase I inhibitor deoxymannojirimycin, revealed that epitope A may be formed by a mannose-rich sugar chain and epitope D might represent a complex carbohydrate structure in the mature glycoprotein, while the epitopes B and C are formed by the protein moiety. Concanavalin A reduced the binding of monoclonal antibody to epitope A by 78%. Binding to epitope D was blocked by 73% with wheat germ lectin, and by more than 99% with sialic acid; epitopes B and C were unaffected by any of the lectins or sugars tested. The immunological cross-reactivity with DPP IV from Morris hepatoma 7777 was demonstrated with monoclonal antibodies against epitopes A-C. Epitope D was not recognized on hepatoma DPP IV. However, in addition to DPP IV, four hepatoma plasma membrane glycoproteins were precipitated by the monoclonal antibody against the epitope D, indicating that this epitope is not uniquely restricted to DPP IV.

Animals↗