Search PubMed⌕ Search

Biomedical subjects

M Graf

Publications and source records attributed to M Graf.

At least 127 records · Page 7Linked to original sources
PubMed1983

Involvement of preoptic-anterior hypothalamic GABA neurons in the regulation of pituitary LH and prolactin release.

The effects of intraventricular injections of the highly specific gamma-amino-butyric acid (GABA) agonist muscimol (5 nmol/animal) on blood LH and prolactin levels were measured in ovariectomized (ovx) and in ovx estrogen-progesterone (OEP) primed rats. While the drug stimulated pituitary prolactin release in both experimental groups, pituitary LH release was significantly inhibited in the ovx animals. Muscimol was without any effect on LH levels in ovx-OEP primed rats. Bilateral implantation of tubes containing a muscimol-mannitol mixture into the medial preoptic/anterior hypothalamic (MPO/AH) area abolished pulsatile LH release whereas blood prolactin values were elevated. The intraventricular injection of GABA (8 mumol) also reduced LH and increased prolactin levels in the blood. Measurements of catecholamine turnover rates in the MPO/AH and in the mediobasal hypothalamus (MBH) yielded reduced preoptic but unchanged hypothalamic norepinephrine (NE) and stimulated hypothalamic dopamine (DA) turnover. In view of the well known stimulatory involvement of the NE system in the mechanism of pulsatile LH release and the inhibitory effect of GABA and its agonist muscimol on pulsatile LH release, it is suggested that GABA inhibits NE release in the MPO/AH by the mechanism of presynaptic inhibition. The observation that muscimol is unable to suppress LH release in vox OEP-primed rats may indicate that those estrogen receptive neurons in the MPO/AH which mediate the negative feedback action of the steroid may use GABA as neurotransmitter and that they are the neurons which inhibit NE release. The inhibitory effect of locally implanted muscimol into the MPO/AH also supports this hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

The value of the edrophonium tonography in the diagnosis of myasthenia gravis.

Tonography of the eye was performed after administration of 10 mg edrophonium chloride (Tensilon) in 13 patients with clinically diagnosed myasthenia gravis. In ten of these patients repetitive nerve stimulation was used to examine the function of the motor end-plate. A significant pressure rise (more than 2 mm Hg) within the 1st min after edrophonium administration was observed in three patients (four eyes), whereas eight of the ten patients who underwent nerve stimulation showed positive results. The edrophonium tonogram test does not seem to be significant enough to define the diagnosis in early myasthenia gravis. Beyond this, these tests might have lost some of their value due to the introduction of antibody analysis against acetylcholine receptors, which serve as a very sensitive diagnostic tool now.

Adolescent↗
PubMed1982

Adrenergic mechanisms and blood pressure regulation in diabetes mellitus.

Changes in blood pressure (BP) and plasma norepinephrine (NE) following various stimuli of the sympathetic, nervous system were studied in six healthy subjects and in 17 diabetic patients. The latter were subdivided in three groups: (1) six patients with neither peripheral neuropathy nor autonomic dysregulation, (2) six patients with severe peripheral neuropathy without autonomic dysregulation, and (3) five patients with autonomic dysregulation, three of whom suffered also from peripheral neuropathy. The following procedures were performed: (1) cold pressor test (2 min), (2) mechanical irritation of the skin by suction (0.75 kg/cm2, 10 min), (3) orthostasis (10 min), and (4) i.v. infusion of NE (50, 100, 200 ng kg-1 min-1 for 15 min each). Both the stimulated endogenous plasma NE levels and BP response to exogenous NE were the same in normal subjects, in diabetic controls and in diabetics with peripheral neuropathy without autonomic dysregulation. In contrast, diabetics with postural hypotension showed a less pronounced release of NE to standing (P less than 0.05), but not to cold pressor test and mechanical skin irritation. Furthermore, they showed increased vasoreactivity to the highest dose (P less than 0.05), but not to the lower doses of exogenous NE. Thus NE release and adrenergic BP regulation seem to be altered only in diabetics with clinical signs of autonomic dysregulation. These alterations can only be evaluated when patients are exposed to stimuli of higher intensity, such as orthostasis or infusion of a high NE dose.

Adult↗
PubMed1982

DSIP-induced changes of the daily concentrations of brain neurotransmitters and plasma proteins in rats.

The influence of delta sleep-inducing peptide (DSIP) on the brain neurotransmitters 5-HT, dopamine and norepinephrine and plasma proteins/corticosterone concentrations for four time points within the 24 hr following IV injection of 30 nmol/kg was investigated in rats. DSIP administered in the morning or in the evening respectively induced changes in nearly all measured parameters. Different effects were observed for different times of administration. The most marked changes were found in the level of serotonin during daytime. In view of the multivariate results obtained by measuring several parameters at multiple time points, a method was developed to describe the time-dependent changes. By means of "circadian rhythm statistics" based on a statistical likelihood analysis we found that multiple and different changes within the factor's daily variation are induced by one injection of DSIP. A multidimensional scaling of the results provides further insights into the correlations of the DSIP-induced effects on plasma and brain factors which are therefore tentatively termed "programming functions." These apparently involve not just sleep induction but also act on multiple parameters within the 24 hr rest-activity period.

Animals↗
PubMed1981

A simplified radioimmunological method for the determination of human beta-endorphin in cerebrospinal fluid.

Human beta-endorphin-like immunoreactive substances (beta h-EI) in human cerebrospinal fluid (CSF) were determined radioimmunologically. The cross reactivity of the antibodies to human beta-endorphin (beta h-E) amounted to 40% for human beta-lipotropin (beta h-LPH) whilst it was less than 1% for leu- and metenkephalin, alpha- and gamma-endorphin, fraction I and II [5], substance P and alpha-MSH. Prior to radioimmunological determination, an adsorbtion of beta h-EI from CSF with silicic acid was carried out and followed by a desorbtion, using a mixture of aceton/hydrochloric acid. This method was chosen because of the ratio of beta h-LPH to beta h-E in the desorbate can be shifted in favour of beta h-E owing to the variation in recoveries r (r beta h-LPH = 33%, r beta h-E = 64%). On the one hand, this enables a more specific determination of beta h-E and, on the other hand, and separation of any peptidase than may be present [9]. An adsorbtion/desorbtion of 2 ml CSF surfaces to prove the presence of 20-150 pg/ml (65-48 fmol/ml) of beta h-EI. The CSF of 28 patients with various neurological diseases was examined and 24 of them had concentrations of 20-70 pg/ml beta h-EI. The remaining four which had concentrations less than 20 pg/ml, came from meningitis patients undergoing corticoid therapy. A purchasable RIA kid was tested for its determination of beta h-E and was found to be unsuitable.

Antibody Specificity↗
PubMed1981

The present status of research in burn toxins.

Modern intensive care combined with current improvements in the specific, systemic and local therapy of burns has delayed the mortal effects of severe burns. Nor has there been any significant improvement in this mortality during the last decade. The occurrence of uncontrollable infection and sepsis due to gram-negative bacteria or fungi as the basic cause of death was not a satisfactory explanation. So, progress should only be expected from a new concept in burn treatment. This new concept should be to view the burn disease as being caused by toxic factors induced by thermal injury to the skin. Electron-microscope studies in mice and rats have revealed similar mitochondrial alterations in hepatocytes after either a sublethal controlled burn injury or an intraperitoneal application of an equivalent dose, of a cutaneous burn toxin. The intraperitoneal injection of different amounts of the burn toxin indicated, that the extent of the mitochondrial changes correlated directly with the dose of toxin. Investigations of liver metabolism suggested an inhibition of the oxygenation chain. The incubation of isolated liver cells together with the burn toxin demonstrated by scanning electron microscopy a direct cytotoxic effect of the burn toxin. In animal tests the pathogenic effect of the burn toxin could be prevented by treatment with an antitoxic IgG generated in sheep. The fatal sepsis of severely burned patients is the consequence of a decreased host defence against infections, which is caused by a primary and general toxic alteration of the whole organism. One important aspect of treatment should therefore be the elimination of burn toxins. To achieve this management should include primary excision of the burns, local application of nonabsorbable protein-complex-binding substances and specific passive immunotherapy with an antitoxic IgG.

Adenosine Diphosphate↗
PubMed1981

Effects of repeated DSIP and DSIP-P administration on the circadian locomotor activity of rats.

Daily intravenous evening injections of 30 nmol/kg DSIP (Delta Sleep-Inducing Peptide) in rats adapted to a constant 24 hr light:dark cycle produced changes in the circadian locomotor behavior. After 3 days the normally high locomotor activity during the dark phase was reduced while during the light (sleeping) phase the animals became relatively more active. Similar, but more rapid and more marked changes were observed (with the same schedule of injections) after 0.1 nmol/kg DSIP-P (the analogue of DSIP phosphorylated at the serine in position 7). In fact the peptide and its analogue induced a relative reversal or shift of the circadian locomotor activity phases opposite to the persisting light:dark conditions (=Zeitgeber). This suggests that DSIP exerts rather complex "programming" effects on the circadian activities and has more than just a sleep-inducing activity.

Animals↗
PubMed1981

Histochemical localization of cathepsin B at the invasion front of the rabbit V2 carcinoma.

To clarify the role of cathepsin B in tumor invasion, the enzyme was visualized in tissue frozen sections of the subcutaneously growing rabbit V2 carcinoma. Localization of cathepsin B was achieved by immunofluorescent staining and by enzyme histochemistry. For the former approach, a sheep antiserum was raised against purified cathepsin B from rabbit liver. The antibodies, isolated by immunoadsorption, reacted monospecifically with rabbit liver cathepsin B in Ouchterlony double diffusion and in immunoelectrophoresis. In the enzyme histochemical assay, Z-Ala-Arg-Arg-methoxynaphtylamide was used as fluorogenic substrate and nitrosalicylaldehyde as coupling agent. With both methods, cathepsin B was found to be localized within fibroblasts and leukocytes assembled at the tumor invasion front. In addition, immunofluorescent staining demonstrated the occurrence of the enzyme in the extracellular matrix surrounding tumor cell clusters. Carcinoma cells always remained unstained. The conclusion is drawn that cathepsin B is chiefly produced by host cells which are stimulated to increase synthesis and to release the enzyme under the influence of the tumor. A dual function can be ascribed to cathepsin B concentrated in the vicinity of the tumor: it operates intracellularly (in host cells) through degradation of endocytosed protein and extracellularly through activation of collagenase. The resulting lytic action on host structures appears to be a prerequisite for local spread of the V2 carcinoma.

Animals↗
PubMed1979

[The effect of 1-deamino-8-D-arginine vasopressin (DDAVP) on blood coagulation in patients with hemophilia A and in healthy men].

DDAVP, a synthetic vasopressin analogue, causes a sustained increase of factor VIII in blood. The drug (0.4 micrograms/kg) was repeatedly infused into 13 hemophilics and 5 healthy men in order to study the kinetics of the elicited antihemophilic factor (AHF). The AHF increase and disappearance were found to be strictly related to the severity of the coagulation defect. Thus, data were obtained which will form a basis for rational therapeutic use of DDAVP in hemophilia. The DDAVP effect was completely independent of the presence of AHF in the circulation and was not associated with activation of clotting or platelets.

Arginine Vasopressin↗
PubMed1979

Shape change reaction of platelets in protein-free medium: ultramorphology.

Transmission and scanning electron microscopy indicate that rabbit platelets incubated in protein-poor medium retain their reactivity to shape change-inducing agents such as 5-hydroxytryptamine, adenosine-5'-diphosphate and chlorpromazine. Such platelets may be used as models for drug-membrane interactions, e.g. in neuronal cells.

Adenosine Diphosphate↗
PubMed1979

The fluorescence and bright field microscopic demonstration of cathepsin B in human fibroblasts.

Cathepsin B was demonstrated cytochemically in human fibroblasts with Z-Ala-Arg-Arg-2-(4-methoxy)naphtylamide as substrate. The enzyme was visualized in the bright field microscope with the diazonium salt Fast Blue B as coupling reagent and in the fluorescence microscope with 5-nitrosalicylaldehyde. With both methods cathepsin B was found in small granules distributed throughout the cytoplasm.

Carcinoma, Squamous Cell↗
PubMed1979

EEG, pattern-evoked potentials and nerve conduction velocity in a family with adrenoleucodystrophy.

In a family with 8 children one case of adrenoleucodystrophy (ALD), verified by autopsy, 2 cases with clinical signs of ALD and four other clinically healthy subjects with pathological ACTH tests were found. As an initial sign in the EEG, temporo-occipital slowing occurred. Further EEG studies showed spread of the primary local abnormalities, indicating diffuse brain dysfunction during progression of the disease. Terminal EEG flattening may be characteristic for late stages of the disease. No correlation could be established between lateralization, paroxysms and actual stage of the disease. Abnormal EEGs occurred not only in clinically and subclinically affected male patients, but also in a girl, who might be a carrier of ALD. Visual evoked potentials showed an increased latency of the P2 wave in the clinically, and in one subclinically, affected subjects. Motor nerve conduction velocity was reduced in only 2 patients. Antidromic sensory nerve conduction velocity of the median nerve was normal in all patients.

Addison Disease↗
PubMed1979

Shape change of blood platelets--a model for cerebral 5-hydroxytryptamine receptors?

1. In blood platelets of rabbits isolated by a stractan gradient and incubated in a protein-poor medium, tryptamine, 5-hydroxytryptamine (5-HT) and derivatives, quipazine and mescaline caused a shape change. This shape change was inhibited by low concentrations of methysergide. 2. The most potent antagonists of the 5-HT-induced shape change included ergoline derivatives and neuroleptic drugs, which showed high stereoselectivity. 3. (+)-Lysergic acid diethylamide ((+)-LSD), psilocine and some N',N'-dimethylated tryptamines acted as mixed agonist-antagonists. 4. The compounds found to be agonists or mixed agonist-antagonists on platelets have previously been shown to act also as 5-HT agonists in the central nervous system (CNS). 5. With regard to 5-HT antagonists, the 5-HT receptors of platelets reacted differently from those described earlier in brain areas with dense 5-hydroxytryptaminergic innervation, but showed similarities to 5-HT receptors investigated previously in spinal cord, cerebral cortex and possibly reticular formation. 6. It is concluded that platelets may be considered with caution as models for some, but not for all, 5-HT receptors in the CNS.

Adenosine Diphosphate↗
PubMed1979

Blood platelets as models for central 5-hydroxytryptaminergic neurons.

Blood platelets resemble 5-hydroxytryptamine (5HT) neurons of the central nervous system (CNS) with regard to uptake kinetics of 5HT at the plasma membrane and potencies of 5HT uptake inhibitors at this membrane. Furthermore, by comparing 5HT uptake in normal and reserpinized platelets the site of action of uptake inhibitors (plasma membrane, intracellular amine storage organelles) may be determined. The specific 5HT receptors of platelets whose stimulation induces a reversible shape change of platelets seem to react to drugs in a similar way as 5HT receptors of some CNS-regions such as spinal cord, cortex and possibly reticular formation. In other CNS areas e.g. those with dense 5HT innervation and the hippocampus the 5HT receptors show a reaction to drugs which is partially different from that of the platelet receptors. In other respects e.g. the synthesis and turnover of 5HT platelets do not resemble 5HT neurons. It is concluded that platelets may be used with caution as models for 5HT-neurons with regard to some aspect of 5HT-dynamics.

Animals↗