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C J Wiedermann

Publications and source records attributed to C J Wiedermann.

At least 127 records · Page 7Linked to original sources
PubMed1989

Bombesin-like peptides as growth factors.

Bombesin-like peptides (BN-LP) are involved in the regulation of many important functions, including sensory transmission, regulation of central autonomic pathways, thermoregulation, pituitary, gastric and pancreatic secretion, food intake and satiety. They also stimulate cellular proliferation in a developmental and tissue-specific manner. Their role in pathogenesis appears to be related to their properties as growth factors, especially in the lung, where BN-LP can induce growth of normal and neoplastic epithelial cells. The formulated hypothesis of autocrine control of small cell lung cancer growth by BN-LP will be tested using specific synthetic bombesin antagonists.

Animals↗
PubMed1989

[Changes in the catecholamine plasma level 3 months after aortocoronary bypass operation].

Plasma catecholamine levels were obtained during diagnostic heart catheterization from the pulmonary artery and aorta and, similarly, renin levels were determined in the pulmonary artery in 31 patients with coronary heart disease and 18 normal controls. 3 months after aorto-coronary bypass surgery the patients with coronary heart disease underwent repeat heart catheterization and the epinephrine, norepinephrine and renin levels were compared with those obtained before operation. Norepinephrine decreased in the aorta from (means +/- SEM) 475 +/- 57 pg/ml to 360 +/- 38 pg/ml (p less than 0.001) postoperatively (controls 225 +/- 21 pg/ml). Epinephrine decreased from 121 +/- 11 pg/ml to 108 +/- 16 pg/ml (p less than 0.001) postoperatively (controls 84 +/- 9 pg/ml). This shows that postoperative relief from myocardial ischemia is associated with normalization of the preoperatively elevated plasma catecholamine levels).

Adult↗
PubMed1989

Interleukin-1 interaction with neuroregulatory systems: selective enhancement by recombinant human and mouse interleukin-1 of in vitro opioid peptide receptor binding in rat brain.

Interleukin-1 (IL-1) exerts a wide variety of biological effects on various cell types and may be regarded as a pleiotropic peptide hormone. Biological evidence suggests that IL-1 participates in the modulation of central nervous system physiology and behaviour in a fashion characteristic of neuroendocrine hormones. In this investigation, recombinant (r) human (h) IL-1 and r mouse (m) IL-1 were examined for their modulation of opioid peptide receptor binding in vitro. Experiments were performed on frozen sections of rat brain. Receptor binding of radiolabeled substance P and of radiolabeled neurotensin were not significantly affected by the presence of rIL-1s. Recombinant IL-1s, however, significantly enhanced specific binding of 125I-beta-endorphin (125I-beta-END) and of D-ala2-(tyrosyl-3,5-3H)enkephalin-(5-D-leucine) (3H-D-ALA), equipotently and in a concentration-dependent manner with maximal activity occurring at a concentration of 10 LAF units/ml. The increased binding of 125I-beta-END and 3H-D-ALA was blocked steroselectively by (-)-naloxone and by etorphine, suggesting detection of opiate receptors. In addition, brain distribution patterns of receptors labeled in the presence of rIL-1s corresponded to patterns previously published for opiate receptors. Autoradiographic visualization of receptors revealed that rIL-1s in the different areas of the brain exert their effect on opioid binding with comparable potencies. The data suggest that certain central nervous system effects of IL-1s may be mediated by their selective interaction with opiatergic systems at the receptor level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

In vitro human polymorphonuclear leukocyte chemokinesis and human monocyte chemotaxis are different activities of aminoterminal and carboxyterminal substance P.

Polymorphonuclear leukocytes (PMNL) are a component of the inflammatory response to neurogenic mediators. Using the micropore filter approach, the authors studied the chemoattracting properties of tachykinins, including substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), and that of calcitonin gene-related peptide (CGRP) for human PMNL in vitro and now show that SP in near nanomolar concentrations stimulates locomotion of human PMNL. Locomotion of PMNL is induced by SP, aminoterminal SP (1-9) and the SP receptor antagonist [D-pro2, D-trp7,9]-SP (DPDT) but not by carboxyterminal SP (3-11), NKA, NKB, or CGRP suggesting that the aminoterminal amino acids arginine and proline are essential residues of SP in activation of PMNL locomotion. In contrast, the migratory effect of SP on monocytes resides in the carboxyterminal SP amino acid sequence, which is in agreement with carboxyterminal, SP receptor-mediated chemotaxis of human monocytes previously shown by others. From the known structure-activity relationships for SP receptors it is concluded that induction of PMNL migration by SP does not involve neurokinin-1 (NK-1), NK-2 or NK-3 receptors. "Checkerboard" analysis reveals that PMNL locomotion by SP is not dependent on concentration gradients and thus represents chemokinesis, which is enhancement of speed and/or frequency of locomotion. One cannot exclude that this action of SP on PMNL is mediated by the aminoterminal sequence via yet unknown SP "receptors".(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitonin Gene-Related Peptide↗
PubMed1989

Substance P receptor-mediated secretion of respiratory glycoconjugate from feline airways in vitro.

The effect of substance P (SP) and other tachykinins on respiratory glycoconjugate (RGC) release was studied in a feline tracheal organ culture system. SP in concentrations of 10(-5) and 10(-6) M stimulated an increase in RGC release of 35 +/- 8% and 18.5 +/- 5%, respectively. The addition of the protease inhibitor aprotinin or the enkephalinase inhibitor thiorphan to the cultures had no effect on the baseline secretion of RGC but markedly potentiated the activity of SP. SP in the presence of aprotinin or thiorphan was active at 10(-8) -10(-9) M concentrations and was more potent at each concentration studied (in the presence of peptidase inhibitors). Among other tachykinins studied, only physalaemin in the presence of aprotinin had a clear stimulatory effect on RGC release at 10(-6) M concentration (26% +/- 5% increase above control, n = 4, p less than 0.02); kassinin, neurokinin A, and neurokinin B had little or no effect on RGC secretion in concentrations of 10(-6) M or less. Autoradiographic studies of [125I]SP binding revealed SP receptor expression in the submucosal glands of the feline trachea. [125I]SP binding was inhibited in the presence of excess unlabeled SP. We conclude that SP receptors are present in the feline tracheal submucosal glands and that binding to SP receptors results in RGC secretion.

Animals↗
PubMed1988

Neuromodulation by polypeptide growth factors: preliminary results on the distribution of epidermal growth factor receptors in adult brain.

Polypeptide growth factors and their receptors are expressed within the brain and neuromodulatory functions are described. Using autoradiography of 125I-epidermal growth factor (EGF) and radioimmunohistochemistry with an antibody to the EGF receptor, we have determined the distribution pattern of the EGF receptor in adult rat brain. The patterns achieved by both methods were similar at every level of the neuroaxis examined. Highest densities of autoradiographic grains were present in the cingulate cortex, cerebral cortex, hippocampus, amygdala and caudate putamen. This pattern of distribution suggests that EGF may have neuromodulatory functions. Common expression of polypeptide receptors by cells of different organ systems constitutes a biochemical basis for homeostatic network regulation.

Animals↗
PubMed1988

Enhanced secretion of immunoreactive bombesin by alveolar macrophages exposed to silica.

Bombesin has recently been identified in alveolar macrophages (AM). Since this peptide has been shown to stimulate fibroblast growth in culture, we wished to determine whether AM exposed to the fibrogenic particle silica in vivo were capable of secreting more bombesin than AM recovered after instilling inert carbon particles to the lung. Rats received 10 mg of either carbon or silica by intratracheal injection and were killed at 3 days or 6 weeks. Both particles induced a rapid inflammatory response, and normal levels of immunoreactive bombesin were measured in lung lavage fluid and in freshly recovered macrophages from all rats. However, incubation of normal AM for 4 h in serum free medium produced a significant increase in bombesin levels measured in supernatants. Bombesin in supernatants of AM cultured after recovery from rats exposed to carbon was at the control value, while AM recovered after silica exposure in vivo secreted increased amounts of bombesin when cultured. Cells recovered 6 wk after instilling silica to the lung and cultured for 4 h secreted 50% more bombesin than control AM. At this time, hydroxyproline measured in the silica-injected lungs was also significantly higher than in controls or carbon-injected rats. These results indicate that AM recovered from lungs after exposure to silica secrete increased amounts of bombesin during the development of pulmonary fibrosis.

Animals↗
PubMed1988

Stimulation of human early and late erythropoietic progenitor cells by insulin: evidence for different mechanisms.

In order to investigate cellular mechanisms involved in insulin stimulation of erythropoiesis, we have studied the response of early (BFU-e) and late (CFU-e) erythroid progenitor cells in a serum-free agar culture system. In this assay system, CFU-e proliferation occurred in media containing low-density lipoproteins, bovine serum albumin, transferrin and recombinant erythropoietin (rEPO). Insulin in physiological concentrations as low as 10(-12)M, added directly to cultures, augmented CFU-e colony formation. This stimulatory effect was also seen when monocyte- and T lymphocyte-depleted cells from normal donors were cultured. In contrast, BFU-e was not stimulated by media devoid of insulin. Occurrence of BFU-e colonies required the presence of insulin in concentrations higher than 10(-8)M. This insulin effect was not dependent on the presence of monocytes and T lymphocytes. Delayed addition studies of rEPO to insulin containing cultures revealed a slight but significant survival rate of CFU-e. A similar survival rate was found for BFU-e. From this, we conclude that insulin stimulates CFU-e by an EPO-like activity. For BFU-e, however, the decline in the number of bursts caused by EPO deprivation implies that insulin does not act directly as a burst-promoting activity but that it probably induces the release of this activity from non-adherent and T lymphocyte-depleted bone marrow cells.

Animals↗
PubMed1988

Vasoactive intestinal peptide receptors in rat spleen and brain: a shared communication network.

The binding sites for [125I]-vasoactive intestinal polypeptide (125I-VIP) in rat spleen and brain were localized using autoradiography. High affinity VIP receptors are present in rat spleen, and competition studies reflect structure-activity relationship typical of VIP receptors elsewhere. In spleen, specific binding of 125I-VIP occurs on red pulp and, most abundantly, on the periarteriolar lymphoid sheath (PALS) of white pulp. Unlabeled VIP competes for binding to both red pulp and white pulp, whereas secretin displaces binding to PALS more potently than to red pulp. This indicates that expression of VIP and/or secretin type receptors is limited to T lymphocytes of white pulp. In red pulp, VIP receptor bearing cells probably are monocytes/macrophages since this is the most abundant red pulp cell type. In the brain, VIP receptors are widely distributed with the highest densities occurring in "sensory" areas. Receptors are abundant in the olfactory bulb, thalamic nuclei, several cranial nuclei and the area postrema. High levels of 125I-VIP binding occurred on inner walls of blood vessels of the brain and spleen. The distribution patterns of receptors for "VIP-ergic signals" in brain and lymphoid tissue indicate interrelatedness of the two organ systems. This may serve as one biochemical rationale for a bio-psycho-social view of health and disease.

Animals↗
PubMed1988

Bombesin-like peptides: neuropeptides with mitogenic activity.

In recent years, a remarkable advance has been made in identifying the extracellular factors that control cell proliferation in a variety of cells. Bombesin-like peptides (BN-LP) are neuropeptides involved in the regulation of many important functions, including sensory transmission, regulation of central autonomic pathways, thermoregulation, pituitary, gastric, and pancreatic secretion, food intake, and satiety. They also may stimulate cellular proliferation in a developmental and tissue-specific manner. Their role in pathogenesis appears to be related to their properties as growth factors, especially in the lung, where BN-LP are proposed to induce growth of normal and neoplastic epithelial cells. The formulated hypothesis of control of SCLC growth by BN-LP will be tested using specific synthetic BN antagonists. Neuronal modulation of the release of BN-LP from neuroepithelial bodies and paracrine effects of BN-LP as sensory neurotransmitters indicate possible pathways of nervous system involvement in tissue development, proliferation, and differentiation, as well as repair processes and wound healing.

Animals↗
PubMed1988

Substance P: the relationship between receptor distribution in rat lung and the capacity of substance P to stimulate vascular permeability.

The interaction of substance P (SP) with specific receptors in intact lung tissue was autoradiographically visualized, using slide-mounted tissue sections of rat lung tissue. SP receptors are highly concentrated in the central airways and are not detectable in peripheral bronchi, vessels, and alveoli. Within central airways, receptor distribution is most concentrated in the epithelium and small vessels in the lamina propria. Smooth muscle in airway or blood vessel walls expressed no detectable SP receptors. Immunohistochemical staining for SP revealed SP-containing nerves in the same areas where the receptors are localized. Displacement curves of SP bound to rat lung indicated that the C-terminal fragment was much more effective than the N-terminal fragment at competing for SP binding. Injection of 0.3 to 30 nmol/kg SP dramatically increased vascular permeability in the trachea and to a lesser extent in the hilus. Peripheral lung failed to respond to SP with increased vascular permeability unless toxic concentrations of SP were employed. SP increased the transudation of protein into the trachea within 5 min of injection, and the extravasated protein persisted through at least 2 h. Both SP and SP(3-11) were capable of stimulating increased vascular permeability, but SP(1-4) was inactive. SP caused mast cell degranulation as reflected in increased plasma histamine levels after SP or SP(3-11) injection, but SP(1-4) had no effect. In order to determine if histamine release caused by SP contributed to the vascular permeability response, the effects of H1 and H2 antihistamine treatment were studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Plasma catecholamine level in diagnostic heart catheterization studies].

Plasma catecholamine levels were obtained during diagnostic heart catheterization from pulmonary artery and aorta before and after injection of contrast medium in 31 patients with coronary heart disease and in 18 normals. The most striking difference between both groups is a significant decline of norepinephrine concentration in aortas after injection of contrast medium in the normals (from 296 +/- 24 [mean +/- SEM] to 225 +/- 21 pg/ml [p less than 0.01]) and no change in patients with coronary heart disease. The cause seems to be rather increased elimination than a decrease of secretion of norepinephrine. Adrenalin shows only partially similar results. Further studies will have to show, what could be the reason for these different reactions of catecholamine level in normals and in patients with coronary heart disease.

Adult↗
PubMed1988

Proliferation and differentiation of human erythropoiesis in vitro: effect of different human lipoprotein species.

In order to permit erythroid proliferation in agar, a serum-free system was developed based on McCoy's 5A medium at pH 8.0, containing deionized and delipidated bovine serum albumin, iron-saturated transferrin, and crude erythropoietin (step III). Addition of the entire complement of serum lipoproteins, termed lipoprotein fraction I (density, less than 1.21 g/ml), increased the number of erythroid colony-forming units and erythroid burst-forming units to numbers indistinguishable from those observed with media containing serum. Moreover, terminal differentiation occurred to fully hemoglobinized normoblasts and even mature erythrocytes. Under these conditions, the erythropoietin dose-response curve obtained when not using serum was comparable to that with serum. Colony formation also displayed a linear relationship to seeding densities down to limiting dilutions. For differential analysis of the main density lipoprotein fractions, sequential ultracentrifugation was performed to isolate very low-density lipoproteins, low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2), and HDL3, which were then added individually to serum-free cultures. Of the main lipoprotein classes, LDL exhibited the most proliferative capacity, followed by HDL2 and HDL3. Our findings indicate that when serum is substituted by well defined compounds including highly purified lipoprotein fractions, a serum-like proliferation and differentiation of human erythropoietic progenitor cells in agar can be obtained.

Bone Marrow↗
PubMed1987

Shared recognition molecules in the brain and lymphoid tissues: the polypeptide mediator network of psychoneuroimmunology.

Nervous and immune systems share specific recognition molecules for signals that originate in both systems. The information substances are polypeptides and their receptors. They comprise the multi-directional information exchange network whereby brain and nervous system function including mood and emotion can be integrated with immune and endocrine system activity throughout the body. This serves as a biochemical rationale for multiple interactions between the systems. It permits us at the tissue, cellular and molecular level to start to understand the "psychoneuroimmunology" of the whole person. Initiated changes in our view of the nervous and immune systems will undoubtedly lead to new strategies for the prophylaxis, diagnosis and treatment of human pathology.

Animals↗
PubMed1987

Sudden death in a young competitive athlete with Wolff-Parkinson-White syndrome.

The case history is documented of a young competitive athlete known to have the electrocardiographic pattern of the Wolff-Parkinson-White syndrome, but considered asymptomatic. On that basis competitive sport was not proscribed. In retrospect, he had experienced occasional tachycardias which were of short duration and ended spontaneously. He never requested medical advice. The boy was first admitted for an attack of rapid heart beating which did not readily subside. He was medicated with prajmalium and left the hospital in stable condition. He died suddenly 10 days after discharge. Autopsy examination of the heart revealed an accessory atrioventricular connection in the posterior septal region. The case history underlines that in some patients with the Wolff-Parkinson-White syndrome the clinical manifestation can be minimal and may be easily ignored by the patient. In retrospect, benign episodes of rapid heart beating most likely were due to a circus movement tachycardia, related to an accessory atrioventricular connection. The sudden death can be attributed to atrial fibrillation with rapid ventricular response via the anomalous connection, despite medical treatment. The observation endorses the potential danger of the Wolff-Parkinson-White syndrome in patients with minimal clinical manifestations. A meticulous histologic study of the atrioventricular junction in hearts of young athletes with sudden and unexplained death is a necessity.

Adolescent↗