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Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 235 records · Page 13Linked to original sources
PubMed1993

Brainstem peptidergic neurons projecting to the medial and lateral thalamus and zona incerta in the rat.

The presence of neuropeptides in brainstem neurons that project to the medial and lateral thalamus and zona incerta has been studied in the rat. Brainstem neurons were retrogradely labeled from the medial and lateral thalamus and the zona incerta by colloidal gold-WGA-HRP and, after silver intensification of the retrograde label, their content of immunoreactivity for nine different neuropeptides was determined after colchicine administration. The medial thalamus and zona incerta both received a large peptidergic input and the lateral thalamus a smaller input from neurons in several brainstem nuclei. These were principally from the locus coeruleus, parabrachial nucleus, the dorsal raphe and the dorsal tegmentum. The principal input to the medial thalamus arose from neurotensin, neuropeptide Y and galanin neurons in the locus coeruleus, neurotensin neurons in the dorsal tegmentum, dynorphin neurons in the parabrachial nucleus and dorsal tegmentum, galanin neurons in the dorsal raphe, substance P neurons in the lateral and dorsal periaqueductal grey and calcitonin gene-related peptide neurons in the nucleus paragigantocellularis. The principal peptidergic input to the zona incerta was from dynorphin neurons in the nucleus of the solitary tract, bombesin neurons in the lateral reticular nucleus, calcitonin gene-related peptide and cholecystokinin neurons in the dorsal tegmentum, substance P, bombesin and galanin neurons in the locus coeruleus, dynorphin and substance P neurons in the lateral periaqueductal grey and cholecystokinin neurons in the substantia nigra, ventral tegmental nucleus and raphe linearis. The principal peptidergic input to the lateral thalamus came from calcitonin gene-related peptide and cholecystokinin neurons in the dorsal tegmentum, calcitonin gene-related peptide and galanin neurons in the locus coeruleus; substance P, neuropeptide Y, galanin and calcitonin gene-related peptide neurons in the dorsal raphe, substance P neurons in the lateral periaqueductal gray, galanin neurons in the nucleus interpedunculus and cholecystokinin neurons in the raphe linearis. In all these cases, from 25% to virtually all of the projection neurons in the brainstem nucleus could contain immunoreactivity to the neuropeptide. A lesser, but significant peptidergic input to the thalamus and zona incerta also arose from the trigeminal nucleus, the substantia nigra, the nucleus of the solitary tract, the lateral reticular nucleus, the interpeduncular nucleus, the raphe linearis, the paragigantocellularis, the inferior olive and ventral tegmental area. Overall, the neuropeptides most frequently present in the projection neurons were substance P, calcitonin gene-related peptide, galanin and cholecystokinin. Bombesin, neuropeptide Y, neurotensin and dynorphin were less common; and enkephalin was present in only a small percentage of projection neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Expression of JUN, KROX, and CREB transcription factors in goldfish and rat retinal ganglion cells following optic nerve lesion is related to axonal sprouting.

Goldfish and rat optic nerves were cut and crushed, respectively, and the expression of the transcription factor proteins c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB was investigated in retinal ganglion cells (RGCs) by immunocytochemistry. Immunoreactivities (IRs) were followed up to 350 days in the goldfish and up to 22 days in the rat. In RGCs of untreated goldfish and rats, all JUN, FOS, and KROX proteins were absent whereas CREB was constitutively expressed. After optic nerve cut in goldfish, a JUN-like immunoreactivity (JUN-IR) appeared in a small number of RGCs of central retina after 24 h, reached a maximum within 5 days, declined after 30 days, and was on a half-maximal level after 50 days. Between 100 and 200 days, JUN-IR was only visible in a few RGCs and was completely absent after 350 days. Specific antibodies against c-JUN, JUN B, and JUN D gave no distinct immunoreactive signal. Thus, we could not determine which member of the JUN family contributed to the JUN-IR. The expression of CREB declined after 5 days. The number of CREB-labeled RGCs was reduced (not significant) and the intensity of labeling faded out. After 50 days, CREB-IR had returned to basal level. c-FOS, FOS B, and KROX-24 could not be detected in goldfish RGCs following optic nerve cut. After optic nerve crush in the rat, c-JUN, JUN D, and KROX-24 appeared in a substantial number of RGCs after 24 h, had a maximal expression after 5 days, and strongly declined after 8 days. c-JUN and KROX-24 were completely absent after 22 days whereas JUN D was still present in a few rat RGCs. The number of CREB-labeled RGCs decreased after 5 days and had declined by 50% after 22 days. Expression of JUN B, c-FOS, FOS B could not be detected in rat RGCs after optic nerve crush. Our data demonstrate that the decrease of CREB and the increase of JUN and KROX-24 transcription factors precedes and parallels both the alteration of de novo protein synthesis and the axonal sprouting, which are long lasting in goldfish and transient in rat.

Animals↗
PubMed1993

Spondylectomy, microsurgical decompression and osteosynthesis in the treatment of complex disorders of the cervical spine.

In 44 patients with complex degenerative, traumatic, neoplastic and infectious disorders of the cervical spine an aggressive surgical approach was used, consisting of spondylectomy, radical microsurgical decompression and osteosynthesis. The patient group consisted of 23 patients with multisegmental cervical spondylosis, 9 patients with primary or metastatic malignant tumour disease spread along the cervical spine, 6 patients with complex cervical trauma and 6 patients with infection affecting one or more cervical segments. Considering the heterogeneity of the group of patients treated, a multitude of neurological symptoms and signs were present. Excruciating pain was the predominant symptom in 84% of the patients, followed by sensory and motor signs of varying degrees in 77% and 65% respectively. Involvement of the long tracts was present in 51%, gait disturbance in 49% and bladder disfunction in 28%. Considering the nature of the underlying disease, in the group with multisegmental cervical spondylosis (MSCS), advanced cervical myelopathy was the predominant clinical symptom, whereas in those patients with trauma, tumour or infection, pain was the leading symptom, followed by disturbed motor and/or sensory function. Altogether 59 vertebrae have been removed in the 44 patients. In 28 patients spondylectomy was performed at one level, in 15 patients at two levels and in one female tumour patient at three levels. In 34 patients an iliac crest bone graft was used and in 10 patients bone cement. Within the observation period, solid fusion was achieved in all patients. In one tumour patient screw loosening was demonstrable at follow-up, but the fusion remained stable. 2 patients with infectious disease required re-operation due to significant loosening of screws and plates. However, after re-stabilization solid fusion was achieved. Considering amelioration of specific pre-operative symptoms and signs, excruciating pain responded best to the stabilizing procedure, with improvement in over 90% of the patients, followed by improvement of sensory and motor deficits in 85% and 82% respectively. Improvement in pre-operative gait disturbance could be achieved in 81% of the patients, while disturbance of bladder function is less likely to improve after surgery with a positive response in only 58%. None of the patients became neurologically worse after surgery. With regard to the underlying disease, patients with MSCS and tumour had the best results with overall improvement in 62% and 75% respectively. While in patients with infection improvement could be achieved in 58%, improvement in trauma patients was demonstrable in only 34% while in 66% the pre-operative clinical status remained unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Colocalisation and covariation of c-JUN transcription factor with galanin in primary afferent neurons and with CGRP in spinal motoneurons following transection of rat sciatic nerve.

The expression of galanin (GAL) in L5 dorsal root ganglia (DRG) and calcitonin gene-related peptide (CGRP) in motoneurons (MN) of lumbar spinal cord and their colocalisation with the nuclear c-JUN protein was investigated by immunocytochemistry following transection of rat sciatic nerve. Expression of c-JUN in L5 DRG neurons increased 10 h following transection. Between 24 h and 10 days 64%-72% of all neurons were labelled. After 50 and 150 days, the end of the observation period, 62% and 27%, respectively, of neurons were labelled by c-JUN. Expression of GAL started after 24 h, reached a maximum between 2 and 10 days in 40-50% of all neurons and persisted in 37% up to 50 days. After 150 days, GAL-IR had returned to basal levels. Between 24 h and 150 days, 75%-86% of all GAL positive neurons showed a nuclear c-JUN immunoreactivity, the maximal number was visible between 2 and 10 days. After 30 days, small diameter neurons showed a slightly increased colocalisation of GAL and c-JUN compared to large diameter neurons. In motoneurons (MN) of lumbar spinal cord of untreated rats, c-JUN was predominantly visible in small diameter MN. The number of c-JUN labelled MN raised 15 h following sciatic nerve transection in both small and large diameter MN. It reached its maximum after 2 days and declined after 40 days. CGRP showed basal expression exclusively in large MN. Its expression raised after 20 h, showed a maximum after 48 h and returned to control levels after 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The KROX-20 transcription factor in the rat central and peripheral nervous systems: novel expression pattern of an immediate early gene-encoded protein.

The KROX-20 protein (also termed EGR-2) is encoded by an immediate early gene cloned by cross-hybridization to the Drosophila melanogaster Krüppel gene. It belongs to a class of transcription factors with zinc finger motifs and binding activity to a transcriptional regulatory DNA element termed the early growth response consensus sequence. In the present study the temporospatial expression of KROX-20 was investigated in the central and peripheral nervous systems of normal rats and after various stimuli known to induce immediate early genes, including epileptic seizures, axotomy, pharmacological treatment with glutamate and alpha-adrenergic receptor antagonists, and peripheral noxious stimulation. Immunocytochemistry was performed with a specific polyclonal antiserum generated against a fusion protein containing KROX-20 sequences. In the central nervous system, KROX-20 protein demonstrated distinct constitutive nuclear expression in specific neuronal subpopulations of the cortex, septum, amygdala, olfactory bulb and hypothalamus. In addition, distinct cytoplasmic immunoreactivity was present in spinal and medullary motoneurons, dorsal root ganglion neurons and a few neuronal cell populations of midbrain and forebrain. In the CNS, KROX-20 was only induced by bicuculline-induced epileptic seizures. Topographically, the postictal increase of KROX-20 levels was restricted to areas with constitutive expression, such as cerebral cortex, fornix and amygdala. Induction of KROX-20 peaked at 4-8 h after onset of seizure activity. No increase in immunoreactivity was observed in the hippocampus, the brain region most severely affected by bicuculline-induced seizures. Transection of central and peripheral nerve fibers did not result in KROX-20 induction in axotomized neurons. However, KROX-20 was induced in Schwann-like cells after transection of the sciatic nerve. In contrast to KROX-20, KROX-24, a related transcription factor of the zinc finger family, was markedly induced in hippocampal and spinal neurons following seizures and peripheral noxious stimulation, respectively, as well as in CNS neurons following axotomy. Our data indicate that KROX-20 represents an immediately early gene product with basal expression in selected neuronal populations of the nervous system and a restricted inducibility after intentional stimuli.

Animals↗
PubMed1993

Does cranial irradiation reduce the risk for bone marrow relapse in acute myelogenous leukemia? Unexpected results of the Childhood Acute Myelogenous Leukemia Study BFM-87.

PURPOSE: One of the goals of study AMA-BFM-87 was to test prospectively in acute myelogenous leukemia (AML) patients if cranial irradiation could be replaced by late intensification therapy with high-dose cytarabine (Ara-C) and etoposide (VP-16). PATIENTS AND METHODS: Patients with a low risk of CNS relapses (ie, no initial CNS disease, WBC count at diagnosis < or = 70.000/microL) were randomized for irradiation (group A, 31 patients). In 25 patients (group B), randomization was refused. As interim results showed no increase of CNS relapses in nonirradiated patients, prophylactic irradiation was discontinued after 2 1/2 years to prevent unnecessary CNS toxicity. Forty-four patients (group C) entered the study after randomization had been stopped. RESULTS: In all patients with a low risk of CNS recurrences (n = 100), a significantly higher probability of relapse-free interval (pRFI) of 5 years was found in irradiated patients (pRFI = .78) compared with nonirradiated patients (pRFI = .41) (P = .007). Moreover, a slightly higher incidence of CNS relapses was observed in nonirradiated patients. Due to the small number of patients, this was not observed when randomized patients only were analyzed. In accordance with these findings, the favorable outcome of low-risk patients in the preceding study, AML-BFM-83 (pRFI > .80), could only be reproduced in study AML-BFM-87 in patients who had received cranial irradiation. CONCLUSION: These results indicate that cranial irradiation should be an integral part of the treatment of all AML patients not undergoing bone marrow transplantation. Residual blasts in the CNS may escape systemic chemotherapy and lead to recurrence of the initial disease not only in the CNS, but also in the bone marrow.

Adolescent↗
PubMed1993

[Utilization of CT image data for preparation of thermoradiotherapy].

Medical imaging procedures are providing qualitative and, increasingly, quantitative diagnostic information on the morphology and function of the human organism. As possibilities for communication and data processing continue to grow, they are also being applied in the field of therapy. Taking combined local radiotherapy and thermotherapy for the treatment of uterine carcinoma as an example, this paper describes the integration of the biological-pathological situation into the modelling of isothermal profiles using the patient's image data.

Body Temperature Regulation↗
PubMed1993

Long-lasting expression of JUN and KROX transcription factors and nitric oxide synthase in intrinsic neurons of the rat brain following axotomy.

In adult rats, the medial forebrain bundle (MFB) and mammillothalamic tract (MT) were unilaterally transected, resulting in axotomy of neurons in numerous areas such as the substantia nigra (SN), ventral tegmental area (VTA), nucleus (ncl.) mammillaris (MnM), and ncl. parafascicularis of the thalamus (PF). In these areas, expression of the transcription factor proteins c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-20, KROX-24, and CREB was investigated by immunocytochemistry up to 150 d. In parallel, the expression of nitric oxide synthase (NOS) was investigated both immunocytochemically and by the NADPH-diaphorase reaction (NDP), and the antibody against NOS was further characterized. The colocalization of c-JUN with NDP or NOS was also studied in the axotomized neurons. c-JUN and JUN D became visible in nuclei of many neurons of the ipsilateral MnM, PF, VTA, and SN (predominantly in the pars compacta and those double labeled by tyrosine hydroxylase, TH) after 36 hr, not after 24 hr, following transection of MFB and MT. In MnM, c-JUN and JUN D persisted at a nearly maximal level for up to 150 d. In PF, these proteins returned to control levels after 75 d. Expression of c-JUN and JUN D declined in the VTA after 30 d, but in the SN, it already declined after only 10 d. KROX-24 had a later onset of expression, being visible after 3 d in all investigated areas, and its pattern was similar to that of JUN proteins, although labeling was visible in fewer nuclei and declined earlier. JUN B, c-FOS, FOS B, and KROX-20 were not expressed in these areas, and substantial alterations of CREB immunoreactivity (CREB-IR) could not be detected. A subset of SN neurons (predominantly in the pars reticularis and negative for TH) presented an early and transient expression of all studied JUN, FOS, and KROX-24 proteins within 3 hr of transection that declined between 24 hr and 48 hr to basal levels. This expression pattern is typical of that caused by transynaptic stimulation (probably due to excitation of descending striatal neurons running within the MFB) and was clearly distinct from that evoked by c-JUN, JUN D, and KROX-24 IRs after 36 hr (predominantly in the pars compacta). An ipsilateral increase in NOS and NDP became visible in many neurons of the MnM after 10 d, but not after 5 d, and this persisted up to 150 d. The temporospatial pattern of NDP was similar to the pattern of NOS-IR.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

The antimicrobial actions of taurolin and other preparations on the pathogenic spectrum in dentoalveolar infections.

Bacteriological specimens from a total of 64 patients with six common, highly relevant clinical indications were collected for an in vitro investigation. By means of standard microbiological methods, 149 species of organism were differentiated, and their relative sensitivity to Taurolin, a broad spectrum chemotherapeutic and antitoxin, as well as 5 conventional finished pharmaceuticals were tested in agar diffusion tests. Taurolin, which was tested in 3 different galenic formulations, produced practically identical, but considerably wider zones of inhibition than all other compared products. In contrast to other substances which exhibited a failure rate of up to 24.8%, no gaps in the activity spectrum in the form of the lack of inhibition zone formation were observed.

Anti-Bacterial Agents↗
PubMed1993

[Normal and induced Hg release from different amalgams].

In an experimental investigation of 20 subjects who had no amalgam fillings, the mercury load from artificially applied, standardised amalgam surfaces was tested for one product containing gamma-2 and one free of gamma-2 respectively. The product which contained gamma-2 caused a statistically significant increase in Hg concentrations in the 24-hour urine sample. After challenge with Dimaval, an intensifying effect on the elimination rate could be detected, although all values clearly remained below a toxicologically relevant concentration. In order to avoid unnecessary exposure to heavy metals, the use of gamma-2-free amalgams and, in the long term, the development of optimised filling materials and intensification of prophylactic measures for prevention of dental caries are to be welcomed.

Administration, Oral↗
PubMed1992

[Mercury concentration in the mouth mucosa of patients with amalgam fillings].

Mercury concentrations were measured in specimens of oral mucosa taken during oral surgery from 90 patients (53 men, 37 women, mean age 42 +/- 16 years); 30 of the patients had no amalgam fillings. All the mucosal specimens extended for at least 2-3 mm from the epithelium of the gingival margin and were clinically and radiologically normal. Thirteen patients without metallic fillings of any kind had mercury concentrations of 118.4 +/- 83.7 ng/g tissue, and in 17 patients with precious metal fillings but no amalgam the mean mercury concentrations were 144 +/- 290 ng/g tissue. Seventeen patients with 1-3 amalgam fillings had an average of 1975 +/- 4300 ng/g tissue and in 26 patients with 3-6 amalgam fillings the average concentration was 1158 +/- 2500 ng/g tissue. In 17 patients with more than six amalgam fillings the mean mercury concentration was 2302 +/- 5600 ng/g tissue. Although these results demonstrate a considerable degree of transfer of mercury from the amalgam fillings to the oral mucosa, it had not resulted in any clinically detectable mucosal lesions.

Adult↗
PubMed1992

[Value and limitations of long-term continuous electrocardiographic recording (Holter)].

Long-time recording of ECG (Holter) is a safe method for assessment of objective complaints patients verbalize often imprecisely. The main value of the method lies in the exact correlation of stated symptoms with recorded ECG-anomalies or the exclusion of such a correlation. Furthermore Holter-analysis yields significant prognostic and therapeutic information in certain types of cardiac disease. Its use knows however a certain number of technical and clinical limitations that have to be known for an efficient application in daily practise.

Arrhythmias, Cardiac↗
PubMed1992

The transcription factor CREB, but not immediate-early gene encoded proteins, is expressed in activated microglia of lumbar spinal cord following sciatic nerve transection in the rat.

Expression of CREB, JUN, FOS and KROX-24 proteins was investigated in glial cells of the lumbar spinal cord. In untreated rats, CREB, c-JUN and JUN D were present in glial cells of the ventral and dorsal horn. Following sciatic nerve transection, the number of CREB immunoreactive glial cells increased in both the ipsilateral ventral and dorsal horns between 24 h and 48 h, reached a maximum after 5 days and returned to control levels after 20 days. Counterstaining with Cresyl violet, a general stain of cells, revealed that the increase of CREB positive glial cells was congruent with the increase of the number of glial cells. Staining with GFAP, a marker for astrocytes, showed an increase in intensity of labelling but no change in number of GFAP labelled cells. This indicates a constitutive expression of CREB in activated microglia. The number of glial cells labelled by c-JUN and JUN D did not change, and glial cells were not labelled by FOS and KROX-24 proteins following sciatic nerve transection. These findings demonstrate that proliferation and differentiation of glial cells in vivo can occur in absence of JUN, FOS and KROX proteins.

Animals↗