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M Vogelsang

Publications and source records attributed to M Vogelsang.

16 recordsLinked to original sources
PubMed2000

Lobular distribution pattern of lactate dehydrogenase and 6-phosphogluconate dehydrogenase activity in rat liver.

Lactate dehydrogenase (LDH) and 6-phosphogluconate dehydrogenase (6-PGDH) activities were measured in lobular areas expanding between 3 portal tracts and an efferent central vein in the livers of male Wistar rats, using a Lowry technique. The maximum of LDH activity was found in a nearly uniform broad area in the lobular periphery. From that area values decreased along periportal/septal-->perivenous gradients, but only slightly within that area along the periportal-->septal axis of the vascular septum. Maximum values of 6-PGDH activity were present in an intermediate area close to the central vein demonstrating a rather inhomogeneous distribution pattern without a clear definition of zonal limits. Our data on the distribution pattern of LDH are in agreement with the concept of the metabolic lobulus and are supported by a recent evaluation of the vascular architecture in rat liver. The lobular distribution pattern of 6-PGDH cannot be interpreted without doubt in accordance with that concept.

Animals↗
PubMed1999

In vivo migration of lymphocytes in chronically rejecting rat kidney allografts.

Histological analyses have identified lymphocytes and macrophages as the predominant leukocyte populations that infiltrate organs undergoing chronic rejection. In order to define the time frame of this infiltration, we investigated the in vivo migration pattern of lymphocytes in a well-established rat model of chronic kidney allograft rejection. F344 kidneys were orthotopically transplanted into bilaterally nephrectomized Lewis rats. Recipients were treated with cyclosporin A (1.5 mg/kg/per day) for the first 10 days. After anti-CD18 or vehicle pretreatment, peripheral blood lymphocytes obtained from naive Lewis rats and labeled with 3H-uridine were injected into transplanted rats 12 and 16 weeks after transplantation. Organs were harvested 4, 8, and 12 h thereafter. After 12 weeks, proteinuria developed, accompanied by all signs of chronic rejection including glomerular sclerosis. Labeled lymphocytes rapidly infiltrated grafted kidneys 4 h after injection. Even more lymphocytes had accumulated in the grafts 12 h after injection. After 16 weeks, few lymphocytes had emigrated into the graft at 4 h, while infiltration was most pronounced by 12 h. Pretreatment with anti-CD18 inhibited the influx of lymphocytes. There was no difference between the patterns of lymphocytes derived from naive and transplanted rats. Our results emphasize the importance of endothelial cells in chronically rejecting kidneys for the control of leukocyte influx. Beta2-integrins may play a central role in determining the transendothelial migration during this process.

Animals↗
PubMed1999

Recurrent pain after lumbar discectomy: the diagnostic value of peridural scar on MRI.

The association between peridural scarring and recurrent pain after lumbar discectomy is much debated. A recently published study found that patients with extensive peridural fibrosis were 3.2 times more likely to experience recurrent radicular pain than those with less extensive scarring. This finding may lead to an overestimation of peridural fibrosis in clinical practice. In a retrospective study we analyzed the records of 53 patients who underwent a lumbar MRI because of recurrent pain after first unilateral microdiscectomy. Patients were classified as those with radicular or non-radicular pain according to history and clinical findings. The diagnosis was confirmed by spinal anesthetic block. The extension of scarring was compared between the two groups of patients. The amount of epidural fibrosis was examined on contrast-enhanced MRI in axial slices subdivided into four quadrants. The amount of fibrosis was divided into four stages in each affected quadrant. We found no differences regarding the amount of peridural fibrosis between patients with radicular pain and patients with non-radicular pain. We conclude that the extent of peridural scarring as defined by MRI is of minor value in the differential diagnosis of recurrent back and leg pain after lumbar microdiscectomy.

Case-Control Studies↗
PubMed1998

Endothelin receptors in the failing and nonfailing human heart.

BACKGROUND: In patients with chronic heart failure (CHF), plasma endothelin-1 (ET-1) levels are increased. We studied whether the cardiac ET-receptor system is altered in CHF patients. METHODS AND RESULTS: We assessed ET-evoked inositol phosphate (IP) formation in slices from right atria and left ventricles from 6 potential heart transplant donors (NFH) and 15 patients with end-stage CHF; in membranes from the same tissues, we studied ET-induced inhibition of isoprenaline- and forskolin-stimulated adenylyl cyclase and ET-receptor density. ET (10[-9] to 10[-6] mol/L, ET-1 >>> ET-3) increased IP formation in right atria and left ventricles through ET(A)-receptor stimulation in a concentration-dependent manner; no difference in potency or efficacy between NFH and CHF hearts was observed. ET-1 (10[-10] to 10[-6] mol/L), via ET(A)-receptor stimulation, inhibited isoprenaline- and forskolin-stimulated adenylyl cyclase in right atria but not in left ventricles, whereas carbachol inhibited adenylyl cyclase in both tissues; again, the potency and efficacy of ET- or carbachol-induced adenylyl cyclase inhibition was not different between NFH and CHF hearts. [125I]ET-1 binding revealed the coexistence of ET(A) and ET(B) receptors in both tissues; however, the density of ET(A) receptors was not significantly different between NFH and CHF hearts. Finally, the immunodetectable amount of left ventricular Gq/11 protein did not differ between NFH and CHF hearts. CONCLUSIONS: In the human heart, ET(A) and ET(B) receptors coexist; however, only ET(A) receptors are of functional importance. In right atria, ET(A) receptors couple to IP formation and inhibition of adenylyl cyclase; in left ventricles, they couple only to IP formation. In end-stage CHF, the functional responsiveness of the cardiac ET(A)-receptor system is not altered.

Adenylyl Cyclases↗
PubMed1998

Mechanism of ET(A)-receptor stimulation-induced increases in intracellular Ca2+ in SK-N-MC cells.

The mechanism underlying endothelin-1 (ET-1)-induced increases in intracellular Ca2+ concentrations in the human neuroblastoma cell-line SK-N-MC was investigated. ET-receptor agonists increased inositol phosphate (IP)-formation (assessed as accumulation of total [3H]-IPs in [3H]-myo-inositol prelabelled cells) and intracellular Ca2+ (assessed by the FURA-2 method) with an order of potency: ET-1 > sarafotoxin 6b (S6b)> ET-3 = S6c; the ETA-receptor antagonist BQ-123 inhibited both responses with apparent pKi-values of 8.3 and 8.6, respectively, while the ETB-receptor antagonist BQ-788 did not. Pretreatment of the cells with pertussis toxin (PTX, 500 ng ml(-1) overnight) reduced ET-1-induced Ca2+ increases by 46+/-5%, but rather enhanced ET-1-induced IP-formation. Chelation of extracellular Ca2+ by 5 mM EGTA did not affect ET-1-induced IP-formation. However, in the presence of 5 mM EGTA or SKF 96365, an inhibitor of receptor mediated Ca2+ influx (1.0-3.0 x 10(-5) M) ET-1-induced Ca2+ increases were inhibited in normal, but not in PTX-treated cells. [125I]-ET-1 binding studies as well as mRNA expression studies (by RT-PCR) detected only ETA-receptors whereas expression of ETB-receptor mRNA was marginal. ET-1 (10(-8) M) inhibited isoprenaline-evoked cyclic AMP increases; this was antagonized by BQ-123, not affected by BQ-788 and abolished by PTX-treatment. We conclude that SK-N-MC cells contain a homogeneous population of ETA-receptors that couple to IP-formation and inhibition of cyclic AMP formation. Stimulation of these ETA-receptors increases intracellular Ca2+ by at least two mechanisms: a PTX-insensitive IP-mediated Ca2+ mobilization from intracellular stores and a PTX-sensitive influx of extracellular Ca2+.

Adrenergic beta-Agonists↗
PubMed1998

Diminished responsiveness of Gs-coupled receptors in severely failing human hearts: no difference in dilated versus ischemic cardiomyopathy.

In end-stage heart failure, cardiac beta-adrenoceptors are decreased and cardiac Gi protein is increased. We assessed beta-adrenoceptors, G proteins, and effects of several beta-adrenoceptor agonists, histamine, and 5-HT on adenylyl cyclase activity in right and left atria and left ventricles and on left ventricular contractility in six potential heart transplant donors (nonfailing hearts; NFHs) and in nine patients with end-stage dilated cardiomyopathy (DCM) and 11 patients with end-stage ischemic cardiomyopathy (ICM) to establish whether the functional responsiveness of all cardiac Gs-coupled receptors is reduced. Beta-adrenoceptors were reduced in all three tissues; in DCM, beta1-adrenoceptors were more markedly downregulated; in ICM, both beta1- and beta2-adrenoceptors were diminished. In all three tissues, isoprenaline-, terbutaline-, histamine- and 5-HT-induced adenylyl cyclase activation was reduced similarly in DCM and ICM. Moreover, in DCM and ICM, guanosine triphosphate (GTP)- (involving Gs and Gi) activated adenylyl cyclase was significantly diminished, whereas NaF-activated (involving only Gs) and Mn2+-activated (acting at the catalytic unit of the enzyme) adenylyl cyclase was unaltered. Left ventricular positive inotropic responses to beta1- (noradrenaline, dopamine, and dobutamine), beta2- (terbutaline), and beta1- and beta2-adrenoceptors (isoprenaline, adrenaline, and epinine), as well as H2-receptor (histamine) stimulation were significantly reduced. The extent of reduction was not different for each agonist in ICM and DCM. We conclude that in DCM and ICM, functional responsiveness of all cardiac Gs-coupled receptors is similarly reduced.

Adenylyl Cyclases↗
PubMed1995

Acetylcholine induces different cutaneous sensations in atopic and non-atopic subjects.

The mediators eliciting pruritus in atopic eczema are a matter of discussion, since several substances may be involved and histamine is unlikely to be the main agent. Hence, in this study we examined the cutaneous sensations and vascular reactions in 15 patients with atopic eczema and in 15 non-atopic subjects after i.c. injection of acetylcholine (Ach, 0,5 M, 20 microliter) or buffered saline, respectively. The sensory perceptions were rated by a visual analogue scale (VAS) as to quality and intensity, and the vascular reactions were monitored by laser Doppler flowmetry and evaluated planimetrically as to flare and wheal extension. The flares and wheals in both groups were similar; yet the cutaneous sensations significantly differed, since all patients with atopic eczema complained of "pure" itching after Ach-injection, whereas the controls reported a burning pain. The patients with atopic eczema started their ratings significantly earlier and rated significantly longer than the controls. Our results provide evidence that Ach may play an important role in the etiology of pruritus in atopic eczema patients.

Acetylcholine↗
PubMed1994

Positive inotropic effects of the beta 2-adrenoceptor agonist terbutaline in the human heart: effects of long-term beta 1-adrenoceptor antagonist treatment.

OBJECTIVES: This study was conducted to determine whether activation of cardiac beta 2-adrenoceptors increases contractility in humans and whether this is affected by long-term beta 1-adrenoceptor antagonist treatment. BACKGROUND: Coexistence of beta 1- and beta 2-adrenoceptors in the human heart is generally accepted. The functional importance of cardiac beta 2-adrenoceptors for increases in contractility in humans, however, has not been completely established. METHODS: We studied 1) the beta-adrenoceptor subtype mediating positive inotropic effects of the beta 2-adrenoceptor agonist terbutaline in vitro (on right atrial and left ventricular preparations from nonfailing human hearts) and increases in contractility (by measurement of systolic time intervals) in vivo in seven healthy male volunteers; and 2) in vivo whether long-term treatment of volunteers with the beta 1-adrenoceptor antagonist bisoprolol affects terbutaline-induced increases in contractility. RESULTS: In vitro terbutaline caused a concentration-dependent increase in atrial and ventricular adenylate cyclase activity and force of contraction. Terbutaline effects were antagonized only by the beta 2-adrenoceptor antagonist ICI 118,551, indicating that they were mediated by beta 2-adrenoceptor stimulation. In vivo intravenous infusions of terbutaline (dose range 25 to 300 ng/kg body weight per min for 15 min) dose dependently increased heart rate and shortened the pre-ejection period and heart rate-corrected electromechanical systole (QS2) time. These effects are mediated predominantly by beta 2-adrenoceptor stimulation because they were only marginally affected by the beta 1-adrenoceptor antagonist bisoprolol (1 x 10 mg orally), either given 2 h before infusion or long term for 3 weeks. CONCLUSIONS: Stimulation of cardiac beta 2-adrenoceptors in humans causes not only in vitro but also in vivo positive inotropic effects. Long-term beta 1-adrenoceptor antagonist treatment does not considerably affect beta 2-adrenoceptor-mediated in vivo increases in contractility. Thus, it may be possible to treat patients with chronic heart failure and long-term beta 1-adrenoceptor antagonist therapy with beta 2-adrenoceptor agonists if immediate inotropic support is needed.

Adenylyl Cyclases↗
PubMed1994

Endothelin ETA-receptors couple to inositol phosphate formation and inhibition of adenylate cyclase in human right atrium.

To study signal transduction pathways of endothelin (ET) in human heart, we assessed, in isolated human right atria, the effects of ET-1 and ET-3 on inositol phosphate (IP) formation and on the adenylate cyclase/cyclic AMP system. In right atrial slices, ET-1 (10(-10)-10(-6)M) concentration-dependently increased [3H]IP accumulation and decreased 10-microM isoprenaline-induced or 1-microM forskolin-induced increases in cyclic AMP content. ET-3 was approximately 100 times less potent. The cyclic AMP-decreasing effect of ET-1 (10(-11)-10(-6)M) could also be demonstrated directly in adenylate cyclase assays in right atrial membranes; again, ET-3 was approximately 100 times less potent. We conclude that in human right atrium, ETA receptors couple to two different signal-transduction pathways: IP formation and inhibition of adenylate cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1993

Comparison of the positive inotropic effects of serotonin, histamine, angiotensin II, endothelin and isoprenaline in the isolated human right atrium.

The receptor systems through which serotonin (5-HT), histamine, angiotensin II and endothelin increase the force of contraction were studied in isolated right atria from patients without apparent heart failure. All agonists increased the atrial force of contraction in a concentration-dependent manner; maximal effects, however, were significantly less than those evoked by isoprenaline or Ca2+. 5-HT and histamine, but not angiotensin II and endothelin, activated adenylate cyclase, whereas endothelin and angiotensin II stimulated inositol phosphate generation. Experiments with subtype-selective antagonists revealed that histamine effects were mediated by H2-receptors (sensitive to ranitidine), 5-HT-effects by 5-HT4-receptors (sensitive to SDZ 205-557) and angiotensin II effects by AT1-receptors (sensitive to losartan). We conclude that in human right atria the force of contraction can be increased by cyclic AMP-dependent (histamine, 5-HT) and -independent (angiotensin II, endothelin) pathways. Compared to beta-adrenoceptors, however, all other receptor systems increase the force of contraction only submaximally indicating that the beta-adrenoceptor pathway is the most important physiological mechanism to regulate force of contraction and/or heart rate in the human heart.

Adenylyl Cyclases↗
PubMed1991

Pattern of retinotectal projection in the megachiropteran bat Rousettus aegyptiacus.

The retinotopic organisation of the superior colliculus (SC) in the megachiropteran bat Rousettus aegyptiacus was examined with single and multi-unit recordings and by tracing the retrograde and anterograde transport of horseradish peroxidase (HRP) between the retina and the SC. The pattern of projection of the visual field onto the SC in Rousettus resembles the pattern found in most mammals. The whole of the contralateral visual field is represented and, in addition, a region of the ipsilateral visual field extending 25 degrees beyond the vertical 0 degree meridian. The ipsilateral visual field is represented binocularly in the most anterior 300-500 microns of the rostral pole of the SC. The contralateral visual field up to 25 degrees from the vertical meridian is represented through both eyes for the next 500-800 microns. The peripheral part of the contralateral visual field, 25 degrees-110 degrees from the vertical meridian is seen only by the nasal retina (the monocular crescent) of the contralateral eye and is represented in the caudal part of the SC. Following multiple injections of HRP into one SC, ganglion cells were labeled in both the nasal and temporal hemiretina of the contralateral eye. In the retina ipsilateral to the injection site, labeled cells were restricted to the temporal hemiretina. After injections of HRP into one eye, labeled terminals were found all over the contralateral SC, but in the ipsilateral SC they were restricted to a band that begins 300-500 microns caudal from the rostral pole and extends to the middle of the SC. These results suggest that in Rousettus, unlike the megachiropteran bats described by Pettigrew, Jamieson, Robson, Hall, McAnally, and Cooper (Philosophical Transactions of the Royal Society of London Series B 325:489-559, 1989), the retinotopic organisation of the SC is not primate-like, but follows the general mammalian scheme. As the retinotopic organisation of the SC is not consistent among the megachiropteran bats, the pattern of this projection may not be a useful indicator of their phylogenetic origins.

Animals↗
PubMedDate not supplied

Receptor systems affecting force of contraction in the human heart and their alterations in chronic heart failure.

Catecholamines acting through beta 1- and beta 2-adrenergic receptors cause positive inotropic and chronotropic effects in the human heart. However, recent evidence suggests that in the human heart other receptor systems can also affect heart rate and contractility. Positive inotropic effects can be mediated by receptor systems acting through accumulation of intracellular cyclic adenosine monophosphate (cAMP; Gs-protein-coupled receptors such as 5-hydroxytryptamine(5-HT)4-like, histamine H2, and vasoactive intestinal peptide) or by receptor systems acting independently of cAMP, possibly through the phospholipase C/diacylglycerol/inositol-1,4,5-trisphophate pathway (such as alpha 1-adrenergic, angiotensin II, and endothelin). In the nonfailing human heart, activation of all these receptor systems induces only submaximal positive inotropic effects compared with those caused by beta-adrenergic receptor stimulation, indicating that in humans the cardiac beta-adrenergic receptor/Gs-protein/adenylate cyclase pathway is the most powerful mechanism to increase heart rate and contractility. However, the human heart contains only a few spare receptors for beta-adrenergic receptor-mediated positive inotropic effects and nearly all beta-adrenergic receptors are needed to cause maximal inotropic effects. Thus any decrease in the number of beta-adrenergic receptors will automatically lead to a reduction in functional responsiveness of beta-adrenergic receptors. In chronic heart failure the number and responsiveness of cardiac beta-adrenergic receptors are reduced, presumably because of the enhanced sympathetic drive to the heart and hence endogenous down-regulation by an elevated release of (cardiac-derived) norepinephrine, and this loss in cardiac beta-adrenergic receptor function is strongly related to the severity of the disease. However, beta 1- and beta 2-adrenergic receptors are differentially changed in different forms of heart failure. In dilated cardiomyopathy and possibly in aortic valve disease the number of cardiac beta 1-adrenergic receptors is selectively reduced without alteration in the number of beta 2-adrenergic receptors (although beta 2-adrenergic receptors become somewhat uncoupled). In ischemic cardiomyopathy, mitral valve disease, and possibly tetralogy of Fallot, the number of both beta 1- and beta 2-adrenergic receptors is concomitantly decreased. Because of the lack of a substantial receptor reserve, such a decrease in the number of beta-adrenergic receptors is accompanied by reduced inotropic and chronotropic responses to beta-adrenergic receptor stimulation in vitro and in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMedDate not supplied

Increased abnormal urothelial cells in voided urine following excretory urography.

A prospective study of 45 consecutive patients scheduled for excretory urography demonstrated a statistically significant increase in the proportion of abnormal urothelial cells, including pseudomalignant cells, recovered in the urine between three hours and seven days after urography. The total number of urothelial cells recovered in the urine did not increase at any time. The Millipore filter imprint technique, which allows semiquantitative examination of urothelial cells from urine, is discussed.

Adult↗