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Biomedical subjects

H Winkler

Publications and source records attributed to H Winkler.

At least 127 records · Page 7Linked to original sources
PubMed1994

Bovine posterior pituitary: presence of p65 (synaptotagmin), PC1, PC2 and secretoneurin in large dense core vesicles.

The subcellular distribution of p65 (synaptotagmin), of the endoproteases PC1 and PC2 and of secretoneurin was studied in bovine posterior pituitary by differential and density gradient centrifugation. All these peptides were found to be present in the neurosecretory granules (large dense core vesicles). p65 can therefore participate not only in exocytosis from small synaptic vesicles but also from large dense core vesicles. Secretoneurin is a peptide derived from secretogranin II. Processing of the propeptide apparently occurs during axonal transport of the large dense core vesicles and is complete in the posterior pituitary. Thus, stimulation of the hypothalamic magnocellular neurons can lead to the release of this newly characterized, functional neuropeptide.

Animals↗
PubMed1994

[Amputation injuries of large extremity segments. Clinical management].

Amputating injuries are often combined with multiple trauma. The management of these serious traumas has to consider survival more than restoration of function and extremity preservation. Out of 51 patients with 60 macroamputation injuries only one case was successful in replantation. The leading rule in the treatment of macroamputation still must be life before limb, as our series of the years 1988 up to 1991 clearly shows.

Adult↗
PubMed1994

[Treatment of acromioclavicular joint dislocation by tension band and ligament suture].

From 1. 1. 1988 until 30. 6. 1990 54 patients with acromio-clavicular luxation and 3 patients suffering from lateral fractures of the clavicula were treated with tension-bend-wiring combined to suturing the acromio- and coracoclavicular ligaments at the BG-Unfallklinik Ludwigshafen. In 8 cases (14%) complications due to the implant occurred. Infection was found in 4 cases (7%). 47 patients (82.5%) could be followed clinically with mean follow-up time of 21.5 month. Clinical criteria like interpretation of the result by the patient, clinical and radiological findings were quantitatively and qualitatively interpreted by a score.

Acromioclavicular Joint↗
PubMed1993

Ontogenic development and distribution of mRNAs of chromogranin A and B, secretogranin II, p65 and synaptin/synaptophysin in rat brain.

We have studied by in situ hybridization the mRNA levels of several constituents of transmitter storing vesicles during ontogenic development of rat brain. The following vesicle components were investigated: chromogranin A and B and secretogranin II, representing secretory peptides of large dense core vesicles, and the membrane proteins p65 and synaptin/synaptophysin which are found in both large and small synaptic vesicles but are concentrated in the latter ones. Several ontogenic patterns were observed: concomitant increases of most or all mRNAs in certain brain regions, e.g. in the thalamic nuclei at gestational day 18 or in the cortex at postnatal day 6. For some areas selective increases for the various chromogranin mRNAs occurred, thus throughout development the substantia nigra compacta contained only the chromogranin B mRNA, whereas the lateral and medial geniculate nuclei and the medial tuberal nucleus expressed only secretogranin II mRNA. In the paraventricular hypothalamic nucleus, secretogranin II mRNA declined at P1 and then increased again. In the intermediate cortex there was a rather selective appearance of a high level of chromogranin A mRNA already at gestational day 16. In general the mRNAs for the membrane components become detectable by in situ hybridization together with the chromogranin mRNA, however, in the claustrum a high level of the p65 mRNA is present already at gestational day 16 whereas the chromogranin mRNA only appears at day 20. In some nuclei there was also a differential expression of the membrane components with e.g. the synaptophysin mRNA being present without any concomitant appearance of p65. These results establish that the ontogenic development of the investigated components in many brain areas simply indicate the starting point of biosynthesis of both types of vesicles finally leading to functional synapses. In those cases where a selective dissociation in the biosynthesis of these components occurs, a functional relevance of one component for a certain stage of development might be postulated. Since these data define the time of onset of vesicle biosynthesis in the various brain regions, future studies on single components of these vesicles can be interpreted in the context of the present findings.

Animals↗
PubMed1993

Attraction of human monocytes by the neuropeptide secretoneurin.

Secretoneurin is a newly discovered 33-amino-acid peptide derived from secretogranin II (chromogranin C) that is found in sensory afferent C-fibers. We show here that secretoneurin triggers the selective migration of human monocytes in vitro and in vivo. Combinations of secretoneurin with the sensory neuropeptides, substance P or somatostatin, synergistically stimulate such migration. The attraction of monocytes represents the first established function of secretoneurin as a sensory neuropeptide.

Animals↗
PubMed1993

Different degrees of processing of secretogranin II in large dense core vesicles of bovine adrenal medulla and sympathetic axons correlate with their content of soluble PC1 and PC2.

We investigated the processing of secretogranin II in large dense core vesicles of adrenal medulla and sympathetic nerve. Despite the fact that both types of vesicles have a very similar biochemical composition, the degree of processing of secretogranin II in vesicles from splenic nerve was significantly higher. The endoproteases PC1 and PC2, two likely candidates for secretogranin II cleavage, are found in both types of vesicles, however, relative to secretogranin II the nerve vesicles have a much higher content of these enzymes. This probably explains the fast and more extensive processing of secretogranin II in these vesicles.

Adrenal Medulla↗
PubMed1993

Vesicle monoamine transporters 1 and 2: differential distribution and regulation of their mRNAs in chromaffin and ganglion cells of rat adrenal medulla.

The expression and synthesis regulation of the vesicle monoamine transporter was investigated in rat adrenal medulla. Previous studies established two genes for monoamine transporters by molecular techniques. In rat adrenal medulla, a differential expression of the corresponding mRNAs was found by in situ hybridization. The mRNA of monoamine transporter 2 was localized in chromaffin cells whereas monoamine transporter 1 mRNA occurred only in ganglion cells of the adrenal medulla. Insulin-induced hypoglycemia, a model for short neurogenic stimulation of the adrenal medulla, did not alter steady-state mRNA levels of both monoamine transporters.

Adrenal Medulla↗
PubMed1993

Cytokine-inducible expression in endothelial cells of an I kappa B alpha-like gene is regulated by NF kappa B.

The transient expression of many different genes is mediated by the inducible transcription factor p50-p65 NF kappa B, which in turn is regulated by complex formation with its inhibitor I kappa B alpha. We describe here that in porcine aortic endothelial cells, either IL-1 alpha, TNF alpha or LPS upregulates an inhibitor of NF kappa B which we refer to as ECI-6. ECI-6 is by structural and functional criteria an I kappa B alpha protein, the porcine homologue of MAD-3, pp40 and RL/IF-1. We have studied the promoter of the ECI-6/I kappa B alpha gene and provide three lines of evidence that its expression is directly regulated by NF kappa B. First, the 5' regulatory region of ECI-6/I kappa B alpha contains two sites that bind NF kappa B in electrophoretic mobility shift assays. Second, expression following transfection of an ECI-6/I kappa B alpha promoter-luciferase reporter construct is dependent on a co-transfected NF kappa B-p65 subunit. Third, pretreatment of endothelial cells with antioxidants, agents that inhibit activation of NF kappa B, inhibit the expression of ECI-6/I kappa B alpha. We conclude that the regulated expression of ECI-6/I kappa B alpha could represent a novel feedback mechanism by which NF kappa B downregulates its own activity after transient activation of target genes has been achieved.

Amino Acid Sequence↗
PubMed1993

In situ hybridization: mRNA levels of secretogranin II, VGF and peptidylglycine alpha-amidating monooxygenase in brain of salt-loaded rats.

The mRNA levels of secretogranin II (SgII), VGF and peptidylglycine alpha-amidating monooxygenase (PAM) were studied in brains of salt loaded rats by in situ hybridization. In these rats the levels of the message for secretogranin II and VGF were increased in the paraventricular, supraoptic and retrochiasmatic nuclei and in the subfornical organ. The increases ranged from 416 to 721% for SgII and from 778 to 890% for VGF. The PAM message was also elevated in these brain regions; however, the maximal increase was only 221%. We conclude that the message for all secretory peptides investigated so far, i.e. vasopressin, galanin, secretogranin II and VGF are upregulated to a similar degree in the hypothalamus of salt-located rats. The relative increase in mRNA for the enzyme peptidylglycine alpha-amidating monooxygenase occurred to a much lower extent, and was comparable to the limited changes previously seen for carboxypeptidase H.

Animals↗
PubMed1993

Reserpine causes differential changes in the mRNA levels of chromogranin B, secretogranin II, carboxypeptidase H, alpha-amidating monooxygenase, the vesicular amine transporter and of synaptin/synaptophysin in rat brain.

Brains of rats treated with a high dose of reserpine were analyzed by in situ hybridization. The mRNA levels of several components of large dense core and small synaptic vesicles were determined. After drug treatment the secretogranin II message was elevated in the parvocellular neurons of the paraventricular nucleus, in the zona incerta, dorsal raphe, locus coeruleus and in the nucleus tractus solitarius. The levels of chromogranin B mRNA were increased in the dorsal raphe and in the substantia nigra compacta. In control animals messages for synaptin/synaptophysin could be found in most of the nuclei investigated, that of the vesicular amine transporter was only detectable in substantia nigra compacta, the dorsal raphe and the locus coeruleus whereas those of carboxypeptidase H and the alpha-amidating monooxygenase could only be determined in the paraventricular nucleus. All these messages were not changed after reserpine. We conclude that the chromogranin B/secretogranin II messages are regulated concomitantly with various neuropeptides. They represent useful general markers to identify stimulated neurons. Our results are consistent with the concept that stimulation of neurons leads to an increased synthesis of secretory peptides and consequently to large dense core vesicles filled with higher quanta of peptides.

Animals↗
PubMed1993

Secretoneurin--a neuropeptide generated in brain, adrenal medulla and other endocrine tissues by proteolytic processing of secretogranin II (chromogranin C).

Secretogranin II (chromogranin C), originally described as tyrosine sulfated protein of the anterior pituitary, is present in large dense core vesicles of several endocrine cells and neurons. We raised antisera in rabbits to conjugates of two synthetic peptides (bovine secretogranin 133-151 and rat secretogranin 154-186) flanked in the primary structure of secretogranin II by pairs of basic residues and used them to investigate the proteolytic processing of this protein by immunoblotting and a newly developed radioimmunoassay. The sensitivity of this assay was 30 fmol for secretogranin 154-186 and 60 fmol for secretogranin 133-151. The highest degree of processing of secretogranin II (> 90%) occurs in brain. One of the peptides (secretogranin 133-151) is not generated to any significant extent. The other peptide, secretogranin 154-186, however, is formed in vivo, and in brain the free peptide apparently represents the predominant form. The highest concentrations of secretogranin 154-186 are found in the hypothalamus, two- to six-fold lower levels are present in the hippocampus, caudate nucleus, thalamus and brainstem. These concentrations are comparable to those of established neuropeptides. In order to indicate the special relevance of secretogranin II and of this peptide for brain we have named this peptide secretoneurin. The newly developed radioimmunoassay for this peptide will be a useful tool to establish its physiologic role in brain.

Adrenal Medulla↗
PubMed1993

Secretoneurin releases dopamine from rat striatal slices: a biological effect of a peptide derived from secretogranin II (chromogranin C).

Proteolytic processing of secretogranin II (chromogranin C) in brain leads to the formation of a 33-amino acid peptide which we have named secretoneurin. All the properties of secretoneurin are consistent with the concept that this peptide represents a neuropeptide. However, a biological function has not yet been demonstrated. Therefore, we have now investigated whether secretoneurin could alter transmitter release in brain. Slices of rat caudate-putamen were superfused in an in vitro system and dopamine was measured in the superfusate. Secretoneurin dose-dependently increased the outflow of dopamine. This response was abolished in Ca(2+)-free medium. The secretoneurin-response could also be blocked by preincubation of the peptide with a specific antiserum and was subject to rapid specific and reversible desensitization. This effect on dopamine release constitutes the first discovered biological effect found for a peptide derived from secretogranin II. Thus, secretoneurin can be added to the ever-growing number of neuropeptides.

Animals↗