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Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 271 records · Page 15Linked to original sources
PubMed1991

A microsomal protein is involved in ATP-dependent transport of presecretory proteins into mammalian microsomes.

Ribonucleoparticle (i.e. ribosome and SRP)-independent transport of proteins into mammalian microsomes is stimulated by a cytosolic ATPase which involves proteins belonging to the hsp70 family. Here we addressed the question of whether there are additional nucleoside triphosphate requirements involved in this transport mechanism. We employed a purified presecretory protein which upon solubilization in dimethyl sulfoxide and subsequent dilution into an aqueous buffer was processed by and transported into mammalian microsomes in the absence of the cytosolic ATPase. Membrane insertion of this precursor protein was found to depend on the hydrolysis of ATP and to involve a microsomal protein which can be photoaffinity inactivated with azido-ATP. Furthermore, a microsomal protein with a similar sensitivity towards photoaffinity modification with azido-ATP was observed to be involved in ribonucleoparticle-dependent transport. We suggest that a novel microsomal protein which depends on ATP hydrolysis is involved in membrane insertion of both ribonucleoparticle-dependent and -independent precursor proteins.

Adenosine Triphosphatases↗
PubMed1991

Beat-to-beat detection of ventricular late potentials with high-resolution electrocardiography.

To detect dynamic changes of VLPs we developed a low-noise, HR-ECG with a gain of 10(5)-10(6)X. This system allows the beat-to-beat detection of low-amplitude signals at the bedside in a nonshielded room without any averaging process. Analysis was performed in 39 normal subjects (group A: 27 men, 12 women, mean age, 28 +/- 8 years), in 98 patients with coronary artery disease without documented sustained ventricular tachycardia (group B: 86 men, 12 women, mean age, 59 +/- 10 years) and in 41 patients coronary artery disease with sustained monomorphic ventricular tachycardia (group C: 36 men, 5 women; mean age 63 +/- 9 years). Comparison was made with time-domain signal-averaging (SA-ECG) in all cases at the same electrode position and with identical band-pass filtering. In group A no VLPs were detected; the total filtered QRS duration was 84 +/- 8 msec (mean +/- SD), and the time interval during which the terminal QRS did not exceed 40 microV (I-40) was less than 30 msec in all cases (mean, 17 +/- 6 msec). In group B, VLPs were detected by HR-ECG in 34 of 98 patients (35%); the total QRS duration was 102 +/- 16 msec (mean +/- SD, p less than 0.01 vs group A), and the I-40 was 29 +/- 13 msec (mean +/- SD, p less than 0.01 vs (group A). In group C, VLPs were detected by HR-ECG in 38 of 41 patients (93%); the total QRS duration was 123 +/- 22 msec (mean +/- SD, p less than 0.01 vs group A and group B), and the I-40 was 40 +/- 14 msec (mean +/- SD, p less than 0.01 vs group A and group B). Concordant results between HR-ECG and SA-ECG were observed in 91% of the cases (59 positive and 103 negative results). Late potentials that exhibited dynamic variations were detected by HR-ECG alone in 13 cases, and very low amplitude VLPs were detected by SA-ECG alone in three cases. In conclusion, the present study demonstrates the feasibility of body-surface recording of VLPs on a beat-to-beat basis, without any averaging process, at the bedside in a nonshielded room. This new approach may allow the study of dynamic changes of VLPs during spontaneous ventricular arrhythmias or ischemia.

Coronary Disease↗
PubMed1991

c-JUN-like immunoreactivity in the CNS of the adult rat: basal and transynaptically induced expression of an immediate-early gene.

An immunocytochemical study of dorsal root ganglia, spinal cord and medulla oblongata was performed with antisera against the c-jun proto-oncogene encoded protein. The c-JUN-like immunoreactivity was restricted to the cell nucleus. In the CNS of untreated rats a basal c-JUN-like immunoreactivity was present in the nuclei of two types of neurons: motor and autonomic. Labelled nuclei could be seen in many motoneurons of the ventral horn of the entire length of spinal cord and the lower medulla oblongata, as well as in the area of the nucleus hypoglossus, the dorsal motor nucleus of nucleus vagus, nucleus ambiguus, nucleus facialis, nucleus abducens and motor nucleus of nucleus trigeminus. Additionally, labelled nuclei were found in the preganglionic sympathetic and preganglionic parasympathetic cells of the nucleus intermediolateralis and nucleus intercalatus in the spinal cord. In the medulla oblongata we found a cluster of cells with c-JUN-like immunoreactivity in an area between the dorsomedial part of the oral nucleus spinalis trigeminalis and the lateral border of the knee of facial nerve. Additionally, a second cluster of c-JUN-like immunoreactivity cells was visible between the ventromedial part of the oral nucleus spinalis trigeminalis and the lateral border of the rostral nucleus facialis. Examination of the characteristics of all cell groups with a basal c-JUN-like immunoreactivity in the spinal cord and lower brainstem revealed an overlapping distribution with cholinergic cell groups. Basal c-JUN-like immunoreactivity was also seen in the dorsal root ganglion cells. We examined the factors which can effect the expression of the c-JUN protein. Maximal expression of c-JUN-like immunoreactivity was observed after electrical stimulation of primary afferents. Stimulation of sciatic nerve at a strength sufficient to recruit A delta- and C-fibres produced c-JUN-like immunoreactivity in many nuclei of the ipsilateral dorsal horn of the lumbar spinal cord. c-JUN-like immunoreactivity was first detectable at 30 min following the end of stimulation, reached a maximum after 1 h, remained unchanged for another 1 h and declined to the basal level after 16 h. The distribution of c-JUN-like immunoreactivity in the lumbar cord coincided with the region of termination of sciatic nociceptive afferents. Contralateral c-JUN-like immunoreactivity appeared after 4 h. After noxious mechanical stimulation of the plantar hindpaw c-JUN-like immunoreactivity occurred in the spinal area of termination of nociceptive afferents of the tibial nerve. Noxious stimulation did not provoke additional c-JUN-like immunoreactivity in dorsal root ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Intra-hisian 2:1 atrioventricular block secondary to Lyme disease.

We describe a case of Lyme carditis with intra-hisian 2:1 atrioventricular (AV) block documented by electrophysiological study. To our knowledge, only two cases of AV block at the level of the His bundle has been described in the literature. Sinus rhythm was restored after 4 days of i.v. ceftriaxone.

Atrioventricular Node↗
PubMed1991

[Development and evaluation of a multi-applicator system of endocavitary radiothermotherapy of gynecologic tumors].

An applicator system for the radiothermotherapy of gynecological tumors has been developed. The concept is based on combining high-dose rate afterloading therapy with local hyperthermia (27.12 MHz). The main applicator, the rf-gamma applicator consists of a guide tube for the gamma source, an electrode system and a cooling system. Isodoses and isotherms can be adapted to the individual anatomical-pathological situation presenting. For therapy planning the interaction between the applicators and the perfused tissue was investigated in a theoretical FEM model. In the first step, the SAR-function in the vicinity of the rf-applicator was determined by means of a 2D FEM calculation. In a second step, the 3D temperature fields was determined using linear shape functions. The results of these calculations showed that in every case the hot spots shifted from the applicator surface into the depths of the tissue. With the aid of an infrared camera and a split phantom the calculations were examined in a homogeneous non-perfused tissue model. Thermometry confirmed the accuracy of the results obtained. The radiothermotherapy system described here was tested in animal experiments, and is presently being used in a clinical pilot study.

Animals↗
PubMed1991

Antiarrhythmic therapy for ventricular arrhythmias.

Treatment of ventricular arrhythmias has received great attention during the past 20 years. However, results of recent trials with class I antiarrhythmic drugs in patients after myocardial infarction have raised many questions about the risk-benefit ratio of antiarrhythmic therapy, at least in asymptomatic subjects. Theoretically, the only two reasons to treat ventricular arrhythmias are (a) the presence of symptoms related to the arrhythmia, and (b) the presence of an increased risk of sudden death. The prognostic significance of a ventricular arrhythmia depends on the type of underlying cardiac disease, on the extent of left ventricular dysfunction, on arrhythmia-related symptoms, and on specific characteristics of the ventricular arrhythmia itself. All these factors should be assessed to allow an adequate selection of patients who really need antiarrhythmic therapy (including nonpharmacological modes of treatment), and to allow the identification of patients for whom antiarrhythmic therapy is clearly unnecessary. Such a risk stratification strategy is essential, because many if not all antiarrhythmic agents have potentially serious adverse effects such as proarrhythmic or negative inotropic effects.

Anti-Arrhythmia Agents↗
PubMed1991

Pathophysiological mechanisms of fibromyalgia.

Pain related to fibromyalgia may consist of a complex interaction of nociceptive, neuropathic, dysregulatory central nervous system and psychosomatic mechanisms. Nociceptor pain is based on the excitation of nervous sensors specialized to signal potentially harmful stimuli, i.e., the nociceptors. Metabolic deficiencies in muscle and neurogenic inflammation induced by the release of substance P and other neuropeptides from the peripheral nerve endings may result in chemical sensitization of nociceptors and an ensuing hyperalgesia particularly present in tender points. Neuropathic pain is due to pathological mechanisms within nerve cells and fibers in the peripheral and central nervous system. Pathophysiology may be related to compression (such as in the carpal tunnel syndrome or a vertebral disk herniation) or regeneration of nerves, resulting in ectopic impulse discharges and disturbances of axonal transport. The ensuing neuronal hyperexcitability and trophic changes induced by a disturbed axonal transport system may be major factors of pain in fibromyalgia. Dysregulatory pain denotes pain maintained by dysfunction of efferent control loops. Thus, if spinal motoneuron output results in excessive tension of postural muscle, nociceptors in muscles, tendons and joints might become more excited. Persistent abnormal spinal reflex transmission due to, e.g., peripheral trauma or inappropriate postural habits may result in a vicious circle between muscle hypertension and pain. Similarly, a defective sympathetic control may result in disturbed microcirculation and nociceptor excitation (e.g., in sympathetic algodystrophy). Many symptoms of pain in fibromyalgia (trigger points, pain referral, pain associated with muscle spasm or neurogenic joint immobilization) can be attributed to abnormal control mechanisms in a complex cybernetic system.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1991

[Results after insertion of apical titanium cones in apicoectomy].

In a post-treatment study 50 apicoectomized teeth in 34 patients being treated with apical titanium cones between 1988 and 1990 were registered. After a mean postoperative observation period of 15.3 months, 42 teeth were still in situ and subjected to clinical and radiographical evaluations. Their mobility was measured by the periotest method. A resulting 84% success rate demonstrates the technique to be suitable to safeguard a prolonged lifetime of severe damaged teeth by use of conical pins which guarantee a perfect closing at neoapex.

Adolescent↗
PubMed1990

The KROX-24 protein, a new transcription regulating factor: expression in the rat central nervous system following afferent somatosensory stimulation.

The expression of the protein product encoded by the Krox-24 gene was investigated immunocytochemically in the central nervous system of adult rats. Immunoreactivity (IR) of the KROX-24 protein which is a nuclear transacting transcription factor, showed a pattern of nuclear staining. Basal KROX-24-IR was visible in the superficial layers of spinal dorsal horn and trigeminal nucleus, and in many areas of the brain including the cerebellum, nucleus raphe magnus, colliculi, periaqueductal gray, hypothalamus, geniculate nuclei, caudate putamen, amygdala, hippocampus, lateral septal nucleus, olfactory tubercle and cerebral cortex. Electrical stimulation of sciatic nerve A- and C-fibers, but not of A alpha- and A beta-fibers alone, induced transient expression of KROX-24 in numerous spinal neurons in the termination area of the stimulated nerve. One hour following the onset of this stimulation of the sciatic nerve the distribution of KROX-24-IR was investigated in the brain and compared to untreated rats. In stimulated animals, the KROX-24-IR was induced in many areas including the lateral reticular nucleus, parabrachial nucleus, periaqueductal gray, hypothalamus, amygdala and lateral habenular nucleus.

Action Potentials↗
PubMed1990

Ribonucleoparticle-independent transport of proteins into mammalian microsomes.

There are at least two different mechanisms for the transport of secretory proteins into the mammalian endoplasmic reticulum. Both mechanisms depend on the presence of a signal peptide on the respective precursor protein and involve a signal peptide receptor on the cis-side and signal peptidase on the trans-side of the membrane. Furthermore, both mechanisms involve a membrane component with a cytoplasmically exposed sulfhydryl. The decisive feature of the precursor protein with respect to which of the two mechanisms is used is the chain length of the polypeptide. The critical size seems to be around 70 amino acid residues (including the signal peptide). The one mechanism is used by precursor proteins larger than about 70 amino acid residues and involves two cytosolic ribonucleoparticles and their receptors on the microsomal surface. The other one is used by small precursor proteins and relies on the mature part within the precursor molecule and a cytosolic ATPase.

Amino Acid Sequence↗
PubMed1990

Optimized deglycosylation of glycoproteins by peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine amidase from Flavobacterium meningosepticum.

Peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F(PNGase F) from Flavobacterium meningosepticum is a highly useful enzyme for the structural analysis of N (asparagine)-linked carbohydrate chains derived from glycoproteins. The enzyme was enriched using a published procedure [Tarentino AL, Gomez CM, Plummer TH, Jr (1984) Biochemistry 1985:4665-71; Tarentino AL, Plummer TH, Jr (1987) Methods Enzymol 138:770-78] and further purified by hydrophobic interaction HPLC on a weak hydrophobic TSK-Ether column from which it was eluted by a decreasing gradient of 1.7 M ammonium sulphate in 100 mM sodium phosphate, pH 7.0, containing 5 mM EDTA. To determine the optimal conditions for a complete deglycosylation of glycoproteins by PNGase F, experiments were performed with human alpha 1-acid glycoprotein, because the five complex type carbohydrate chains are quite resistant to enzymic hydrolysis. The influence of different detergents on the enzyme reaction was studied. Complete deglycosylation of human alpha 1-acid glycoprotein was achieved by the use of 60 mU/ml PNGase F in 0.25 M sodium phosphate buffer, pH 8.6, containing 0.2% (w/v) SDS, 20 mM mercaptoethanol and 0.5% Mega-10.

Amidohydrolases↗
PubMed1990

Suppression of a hind limb flexion withdrawal reflex by microinjection of glutamate or morphine into the periaqueductal gray in the rat.

Microinjection into the midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF) of the neuronal excitant glutamate produces analgesia, and suppresses the responses of a fraction of spinal dorsal horn neurons to noxious heat applied to ventral hind paw skin. Microinjection of morphine into the PAG also produces analgesia, but has been reported to frequently facilitate, as well as to suppress or have no effect, on nociceptive spinal neurons. In anesthetized rats, we tested whether (a) glutamate microinjections into PAG or LRF, and (b) morphine microinjections into PAG, affected the isometric force of hind limb withdrawal elicited by the same noxious heat stimuli on the hind paw as used in single-unit studies of dorsal horn neurons. Glutamate (0.5 M; 0.1-0.5 microliter) microinjected at 9/12 PAG and 8/10 LRF sites suppressed the reflex, and had no effect or facilitated the reflex from the remaining sites. Morphine (5 micrograms in 0.5 microliter) microinjected at each of 10 PAG sites suppressed the reflex in a naloxone-reversible manner. Suppression usually began shortly after morphine, peaked at 20-40 min, and lasted greater than 60 min. The integrated flexion reflex thus appears to be more susceptible to chemical midbrain stimulation under these experimental conditions, compared to previous studies of single dorsal horn neurons.

Animals↗