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Biomedical subjects

H Ehrenreich

Publications and source records attributed to H Ehrenreich.

15 recordsLinked to original sources
PubMed1992

Long term monitoring of immunoreactive endothelin-1 and endothelin-3 in ventricular cerebrospinal fluid, plasma, and 24-h urine of patients with subarachnoid hemorrhage.

Endothelins (ETs), peptides that were originally isolated from endothelial cells, have extremely potent and long-lasting vasoconstricting effects on cerebral vessels in vitro and in vivo. Observations that astrocytes produce these peptides and that their ET production can be stimulated, e.g. by thrombin, and potentiated via a self-enhancing autoregulatory mechanism may have shed new light upon the pathogenesis of cerebrovasospasm (CVS). ETs are present at low levels in normal human cerebrospinal fluid (CSF). Few and contradictory reports exist on ET levels in subarachnoid hemorrhage (SAH)-associated CVS. We monitored ventricular CSF, plasma, and 24-h urine levels of immunoreactive endothelin-1 (ET-1) and endothelin-3 (ET-3) in seven patients with SAH, who did (five) or did not (two) develop CVS in the course of their disease, as well as in two patients with different conditions (acoustic neuroma/postoperative meningitis; hydro-/hematocephalus) over 7-19 days. A distinct peak of both ET-1 and ET-3 in CSF of patients with SAH coincided with clinically documented signs of CVS and was absent in CSF of patients with SAH but no CVS. CSF levels of ET-1 and ET-3 displayed a striking parallelism in all subjects. Plasma ET-1 levels were essentially in the normal range. ET-3 was not detectable in plasma under our assay conditions. The excretion profiles of ET-1 and ET-3 in 24-h urine revealed again a predominantly parallel behavior of the two peptides. Interestingly, patients with high ET levels in CSF showed simultaneous peaks in urinary ET excretion, expressed as nanograms per gram of creatinine. Our findings support an association of ETs with the pathogenic events following SAH. The well-documented effects of these peptides on cerebral vessels suggest they are mediators rather than markers of disease.

Adult↗
PubMed1992

Endothelins belong to the assortment of mast cell-derived and mast cell-bound cytokines.

Local accumulation of endothelins (ETs) as cytokine-like factors via autocrine/paracrine mechanisms seems to represent an important aspect of their pathophysiological action. This assumption prompted us to investigate mast cells as a possible source of these peptides. With the use of a combination of high-performance liquid chromatography and a radioimmunoassay specific for endothelin-1 (ET-1), 3-week-old cultures of primary murine bone marrow mast cells (BMMC) as well as various mast cell lines were shown to contain and secrete immunoreactive ET-1. The amounts of this peptide were constitutively high in cellular extracts of BMMC, while there was considerable variation in the basal cellular content among mast cell lines, ranging from high (C57) to undetectable (RBL) levels. Treatment of the cells with the combination of phorbol myristate acetate (PMA) and A23187 for 5 h led to induction of ET-1 production in all cases tested. In contrast to the rapid stimulation by PMA/A23187 of histamine release from BMMC or C57 cells, however, no ET-1 secretory response was noted as early as 30 min after this combined treatment. Moreover, stimulation of mast cells with crosslinked IgE for 30 min or 5 h did not affect ET-1 secretion, suggesting that mast cell ET-1 release is not directly related to mast cell degranulation. After exposure of the cells to crosslinked IgE for 20 h, however, there was a distinct increase in immunoreactive ET-1 in the medium, to approximate 10 times the basal level. Polymerase chain reaction (PCR) analysis of mRNA expression in mast cells revealed that the amount of ET-1 PCR product, which is low or undetectable under nonstimulated conditions, is enhanceable by both PMA/A23187 and crosslinked IgE. The IgE-mediated induction kinetics for ET-1 mRNA parallel the kinetics obtained with PMA/A23187, albeit at somewhat lower levels. With the use of fluorescent ligand binding/flow cytometry as a screening method and a radioreceptor assay as the confirming method, mast cells were found to express a single class of high affinity ET receptors with distinct selectivity for ET-1 and a pharmacological profile resembling that of the ETA type ET receptor. Stimulation of mast cell ET-1 receptors did not provoke histamine release, nor did it result in a mitogenic response of BMMC. In conclusion, mast cells synthesize and secrete ET-1 and have ET receptors, suggesting that ET-1 may participate in mediating mast cell-related long-term changes in the microenvironment, e.g., in smooth muscle tone or the proliferation rate of fibroblasts.

Animals↗
PubMed1991

A vasoactive peptide, endothelin-3, is produced by and specifically binds to primary astrocytes.

Primary rat astrocytes were found by immunohistochemistry to display positive staining for endothelin-3, located predominantly in the perinuclear area. The ability of these cells to produce and release endothelin-3 was confirmed by a combination of reverse-phase HPLC and radioimmunoassay, specific for endothelin-3, which demonstrated immunoreactive peptide in cellular extracts and astrocyte-conditioned medium. In addition, astrocytes were shown to possess a single class of binding sites for endothelin with comparable high affinity for endothelin-1, -2 and -3. These results suggest that astrocytes, by virtue of their ability to produce and secrete endothelin-3, serve as a potential extravascular source of intracerebral vasoregulation capable of influencing regional cerebral blood flow.

Animals↗
PubMed1991

Selective autoregulation of endothelins in primary astrocyte cultures: endothelin receptor-mediated potentiation of endothelin-1 secretion.

Observations that primary rat astrocytes express high-affinity binding sites for endothelins and, in addition, are capable of producing not only endothelin-3 but also endothelin-1 prompted the investigation of a possible relation between endothelin peptides and receptors in these cells. Sarafotoxin S6b, an endothelin receptor agonist, was used as a tool to study endothelin receptor-mediated changes in the secretion of endothelin-1 and -3. The effects of sarafotoxin S6b and endothelin-1 in stimulating inositolphospholipid turnover as well as in inducing AP1 in primary astrocyte cultures were found to be similar. A low cross-reactivity of sarafotoxin S6b with endothelin-1 and -3 in the endothelin radioimmunoassays used here, along with a distinctly different elution position in high-performance liquid chromatography, allowed a clear discrimination between sarafotoxin and endothelins in the culture media. Stimulation of primary rat astrocytes with 10(-7) M sarafotoxin S6b for 1 hour resulted in a substantial increase in endothelin-1 immunoreactivity in the medium. This immunoreactivity reached a peak at 3 hours and showed no further increase after 8 and 24 hours. Treatment of our cultures with phorbol myristate acetate, lipopolysaccharide, tumor necrosis factor alpha, and norepinephrine for 24 hours led to only a moderate elevation of endothelin-1 immunoreactivity. Immunoreactive endothelin-3 was not affected by any of the treatments tested. Thus, our data suggest that endothelins in primary rat astrocytes are subject to selective autoregulation, as demonstrated by the potentiation of endothelin-1 secretion after activation of glial endothelin receptors.

Animals↗
PubMed1990

Endothelins, peptides with potent vasoactive properties, are produced by human macrophages.

Endothelins are peptides, originally isolated from endothelial cells, with potent vasoactive and mitogenic properties. In this study, we demonstrate that human macrophages synthesize and secrete endothelins. Cultured human macrophages were found by immunocytochemistry to stain positively for endothelin 1 and endothelin 3. Their capability to produce and release these peptides was confirmed by a combination of reverse-phase high-performance liquid chromatography and radioimmunoassays, specific for endothelin 1 and 3, respectively. Immunoreactive peptides were identified both in cellular extracts and in macrophage-conditioned medium. The secretion of endothelin 1, but not of endothelin 3, from macrophages could be stimulated 6-10-fold by lipopolysaccharide or phorbol myristate acetate (PMA). Northern blot analysis of total macrophage RNA using an endothelin 1 cDNA probe revealed induction of endothelin mRNA in PMA-treated macrophages. Furthermore, immunoreactive endothelin 1 and 3 were found in U937 cells, a human promonocytic line, and in freshly isolated human monocytes. In contrast, no immunoreactive endothelin was detected in cell extracts from human neutrophils and lymphocytes. The expression of endothelins in tissue macrophages was demonstrated in paraffin sections of human lung using immunohistochemistry. In conclusion, the finding that human macrophages produce endothelins suggests an important role for these peptides in the microenvironment of tissue macrophages. Macrophage-derived endothelins may have an essential function in blood vessel physiology, and aberrant production may contribute to vessel pathology.

Cells, Cultured↗
PubMed1989

Complete bilateral internal ophthalmoplegia as sole clinical sign of botulism: confirmation of diagnosis by single fibre electromyography.

A case of complete bilateral internal ophthalmoplegia as the sole clinical sign of botulism is reported. Diagnosis was immediately confirmed by single-fibre electromyography (SFEMG), which revealed abnormally high blocking (14.3%), contrasting with moderately increased jitter (mean consecutive difference in the extensor digitorum communis muscle, 43.9 microseconds). After giving equine botulinum antitoxin and simultaneous forced emptying of the bowels, ocular symptoms completely disappeared within 2 days. Six days, 5 weeks and 6 months after the first SFEMG study, the jitter was still abnormal, even becoming more so with time. Blocking, however, was only rarely observed in the follow-up studies. It is concluded that SFEMG may serve as a useful and sensitive method for the rapid diagnosis of botulinum intoxication, even in cases where no clinical signs of general muscular weakness are apparent.

Adult↗
PubMed1989

Non-invasive topographic analysis of intestinal activity in man on the basis of acustic phenomena.

In an attempt to find a non-invasive method yielding a comprehensive insight into a patient's intestinal activity, continuous multichannel registration and analysis of acustic phenomena as produced by the intestines were performed. Previous work, described by others, was further developed with respect to topographical interpretation of the data obtained, and to the possible introduction into general clinical use by installing different methods of artifact detection and reduction. To record and process bowel sounds, a device developed for this purpose (Phonoenteroanalyzer PEA-06, G-W Elektronik, Munich, FRG) was used. Five specially designed microphones were placed on the abdominal wall. After amplification and filtering, further processing of the signal was achieved by means of rectifying, peak detection, and logarithmic transformation techniques, yielding a topographically discernible pattern of intestinal activity. Noise and movement artifacts, although a basic problem of this technique, could be adequately managed, e.g., by using a control microphone as well as simultaneous registration of breathing. Ten normal subjects as well as eight patients with manifest or suspected gastrointestinal problems, had their bowel sounds registered either continuously overnight or during adequate stimulatory tests (gastrocolonic response, neostigmine test, rectal distension). Bowel sounds were registrated as short "clicks" or longer lasting, sometimes rhythmically appearing, complex acustic phenomena. Overnight registrations revealed periodical changes in general or local intestinal activity, which in turn showed remarkable interindividual variabilities. Stimulatory tests provoked an enhancement of intestinal activity, which could well be documented with this method. In conclusion, analysis of acustic phenomena provoked by the bowels should henceforth allow an objective, continuous, long-term, non-invasive, indirect, and at any time repeatable topographical registration of intestinal activity.

Adult↗
PubMed1989

Immunoreactive atrial natriuretic peptide (ANP) in endoscopic biopsies of the human gastrointestinal tract.

The human gastrointestinal tract, important for body salt and water balance, was investigated by endoscopic biopsy for the presence of atrial natriuretic peptide (ANP). Using immunohistochemistry, ANP-immunoreactive cells were identified in the lamina epithelialis mucosae of stomach, duodenum, jejunum, colon, and rectum. The findings indicate that ANP plays a role in intestinal salt and water regulation in man. ANP measurements in tissue specimens reached by endoscopic biopsy may be of major interest for future investigations on (patho-)physiological and pharmacological aspects of ANP.

Adult↗
PubMed1988

Stimulation by hCRF of C-peptide release in type 2 diabetics during concomitant opioid receptor blockade.

Administration of synthetic human corticotropin-releasing factor (hCRF, 2 micrograms/kg body weight) during simultaneous application of the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) produced a significant increase in plasma C-peptide levels of six male Type 2 diabetic patients which even exceeded the postprandial values. This stimulatory effect of hCRF/naloxone on plasma C-peptide was less pronounced in six healthy men. hCRF alone did not provoke any reaction of plasma C-peptide in either group. The possibility of a paracrine, CRF-dependent mechanism in pancreatic islets which somehow involves inhibitory opioid receptors is preferentially discussed. Such a mechanism may underlie the stimulatory action of hCRF/naloxone on B cells and would explain the absent reaction of peripheral venous plasma C-peptide to hCRF alone as well as the amplifying effect of simultaneous opioid receptor blockade.

Blood Glucose↗
PubMed1987

Potentiation of the hCRF-induced release of ACTH in man by an opioid antagonist.

Administration of synthetic human corticotropin-releasing factor (hCRF; 2 micrograms/kg body weight) to six normal male subjects produced a significant rise in plasma ACTH, followed by an increase in circulating cortisol. Simultaneous treatment with the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) significantly potentiated the hCRF-induced rise in ACTH and enhanced the cortisol response to hCRF. It is suggested that naloxone acts by antagonizing an inhibitory ultra-short-loop feedback effect of coreleased beta-endorphin on pituitary corticotrophs, thereby amplifying the net effect of hCRF, i.e., the release of ACTH.

Adrenocorticotropic Hormone↗
PubMed1987

Impaired pancreatic polypeptide response to hCRF in type 2 diabetics: restoration to normal by an opioid antagonist.

Administration of synthetic human corticotropin-releasing factor (hCRF, 2 micrograms/kg body weight) to 6 normal men produced a significant rise in plasma pancreatic polypeptide (PP) levels. This PP-stimulating effect of hCRF could not be observed in 6 male Type 2 diabetic patients. Simultaneous application of the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) led to a restoration of the normal PP response to hCRF in the diabetic patients, while in normal subjects, during this combined treatment, the hCRF-induced PP peak occurred somewhat delayed. Our results provide further evidence for a role of hCRF as a stimulatory factor of PP release in normal men. Moreover, it is suggested that endogenous opioids may be part of a modulatory principle co-regulating the secretion of PP. An elevated tone of such an opioidergic PP control system could be responsible for the impaired PP response to hCRF in Type 2 diabetics.

Adult↗
PubMed1985

[Endogenous opioids].

The discovery of the opioid receptors and their corresponding ligands, the opioid peptides, is of fundamental importance as regards our understanding of a variety of functional mechanisms in the central and peripheral nervous system. This review considers the distribution of the multiple opioid peptides within the organism as well as their tissue-specific enzymatic processing. These parameters differ considerably between species. The multiple opioid peptides are paralleled by multiple opioid receptors. These opioid systems affect a broad spectrum of functions, such as behaviour, pain perception, the cardiovascular system, respiration, appetite, gut motility and secretion, water- and electrolyte balance and the complex field of endocrine mechanisms. The task of future pharmacological research is to study these functions by means of more selective opioid agonists and antagonists. An awareness of our present knowledge and of probable findings to come suggests novel therapeutic possibilities in the field of veterinary science.

Animals↗