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Biomedical subjects

B Muller

Publications and source records attributed to B Muller.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effects of cGMP on calcium handling in ATP-stimulated rat resistance arteries.

The mechanisms by which guanosine 3',5'-cyclic monophosphate (cGMP) modulates the contraction induced by ATP were investigated in small mesenteric resistance arteries of the rat. The nitric oxide donors 3-morpholinosydnonimine (SIN-1, 10 microM) and sodium nitroprusside (SNP, 10 microM) increased cGMP but not adenosine 3',5'-cyclic monophosphate (cAMP) content of the tissue. SIN-1, SNP, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 100 microM) inhibited the myosin light chain phosphorylation and the contractile response to ATP. Both effects were completely reversed by the selective inhibitor of cGMP protein kinase, Rp-8-bromoguanosine 3',5'-cyclic monophosphorothioate (30 microM). The sensitivity to Ca2+ of arteries permeabilized with Staphylococcus aureus alpha-toxin (4,000 hemolytic units/ml) was not affected by 8-BrcGMP. The two nitric oxide donors and 8-BrcGMP decreased the rise in intracellular Ca2+ induced by ATP. The vasodilator agents abolished the contractile response to the exogenous calcium in vessels that were exposed to 3 mM ATP after depletion of intracellular Ca2+ stores. Thapsigargin (1 microM), an inhibitor of the sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase, reversed the inhibitory effect of the vasodilator agents when the contraction induced by ATP was elicited in the presence of the Ca2+ entry blocker nitrendipine (1 microM) or in Ca(2+)-free medium. These results show that cGMP inhibits ATP-induced contraction by decreasing intracellular Ca2+ concentration in small resistance arteries. They indicate that this effect results from decreased Ca2+ influx and enhanced Ca2+ sequestration through a thapsigargin-sensitive pump via activation of a cGMP protein kinase.

Adenosine Triphosphate↗
PubMed1994

[Ender nail with interlocking mechanism or dynamic hip screw in pertrochanteric fractures? A prospective study extending its limits].

In a prospective study on 148 patients with trochanteric fractures of the hip we compared the results of two implant-systems: the Ender-nailing modified by the dynamical interlocking method of Kempf and Bitar, and the dynamic hip screw (DHS) of the AO-ASIF. The Ender-method had the shorter operation time, earlier weight-bearing and less septic complications. Fracture consolidation was complete after three months in all cases. But in 8% reosteosynthesis because of hip joint perforations of nails was necessary. The method leads in less cases to anatomical reduction (85%), more often relevant varus (9%) and rotationary (14%) malpositions and functional deficits in hip (25%) and knee joints (9%), compared with the DHS. The DHS had less implant complications, reosteosynthesis was necessary in 4%. Technical failures were seldom. In 96% anatomical reduction could be achieved and the function of the hip was in 87% good to excellent. The Ender-nailing with dynamic interlocking is a system for internal fixation of trochanteric fractures in elder patients. The DHS-system has better functional results. Both systems need to be performed in a very careful, exact surgical procedure, to avoid complications.

Adult↗
PubMed1994

Detection of de novo mutations and analysis of their origin in families with X linked hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (EDA) has been localised to the q12-q13.1 region of the X chromosome by both physical and genetic mapping methods. Although linkage analysis using closely linked flanking markers can clarify the carrier status for many females at risk for the disorder, knowledge of the origin of the mutation in instances of possible de novo mutation is critical for accurate genetic counselling of families. Two methods have been used to confirm de novo mutation in families with EDA and to trace their origin. Direct detection of three de novo molecular deletions, one arising during oogenesis and the other two during spermatogenesis, was achieved by Southern analyses using cosmids isolated from the EDA region as probes. Seven de novo mutations arising during spermatogenesis, and two possible de novo mutations during oogenesis, were identified by an analysis of the cosegregation of the disorder with polymorphic markers closely linked to and flanking the EDA locus. The confirmation and analysis of the origin of the 10 de novo mutations greatly assisted genetic counselling in these families. The apparent 3.5:1 excess of male to female origin of mutation in families studied with unidentified types of mutation is similar to other studies of X linked disorders, and suggests that the majority of these mutations may involve single base pair substitutions.

Adult↗
PubMed1994

Ultrastructure of systemic sclerosis inflammatory myopathy.

Muscle biopsies from 7 patients with systemic sclerosis (SS) and a slowly progressive proximal muscular weakness were studied ultrastructurally. In all cases an inflammatory myopathy was found exhibiting fibre atrophy, occasional fibre necrosis, connective tissue proliferation, filamentous bodies, concentric laminated bodies and a mononuclear cell infiltration formed by lymphocytes, macrophages and mast cells. Capillary abnormalities included alterations of endothelium, thickening and reduplication of basement membrane and the presence of cylindric confronting cisternae. The different associations between muscle diseases and SS are grouped. Our data suggest that SS inflammatory myopathy is a distinct clinical and pathological entity.

Biopsy↗
PubMed1994

[Use of ultrasound in acute and follow-up diagnosis of septic accident surgery].

In 50 patients with infections of soft tissue, bone and joints, ultrasound examination was the first diagnostic procedure performed after clinical and X-ray examination. In 22 soft tissue infections the liquid portion of the infection area could be differentiated. Deep subfascial infections were detected in 7 cases before they were clinically apparent. The results of the ultrasound examination had an influence on the operation performed in 10 cases. In 18 patients with bone infections with abscesses the linkage of the fluid zone to the bone was demonstrable, and in 6 of these cases we saw extramedullary sequestrae as total reflecting parts. Empyema was diagnosed by ultrasound in association with clinical and laboratory parameters in 10 cases, including 3 in which clinical examination had not yet led to a firm suspicion. Real-time sonography influenced the operative treatment (time of intervention, approach) in 36% of all these cases was helpful in the diagnosis in all.

Abscess↗
PubMed1993

Characterization of indolidan- and rolipram-sensitive cyclic nucleotide phosphodiesterases in canine and human cardiac microsomal fractions.

The distribution of phosphodiesterase (PDE) activities was studied in canine cardiac microsomal fractions separated by sucrose density gradient (fractions F1 to Fv1). These fractions were characterized by their 45Ca2+ uptake and release properties, [3H] ryanodine binding [used as sarcoplasmic reticulum (SR) markers] and their [3H]nitrendipine binding (as a T-system marker). The solubilized canine and human SR-enriched membranes were subjected to high performance liquid chromatography and the PDE forms were then analyzed for their kinetic properties and drug sensitivies. In human SR, a notable amount of PDE I hydrolyzing both cAMP and cGMP was characterized; however, its stimulation by calmodulin was reduced. Two selective cAMP-PDE forms were identified in the canine and human cardiac SR-enriched fractions. The major form presents the characteristics of PDE III: an apparent Km value of 0.29 and 0.35 microM in canine and human cardiac SR, respectively, potent inhibition by cGMP and AAL 05 > cilostamide > Cl 930 > indolidan, and insensitivity to rolipram. The other form displays the properties of PDE IV: an apparent Km value of 1.4 and 1.3 microM in canine and human cardiac SR respectively, potent inhibition by rolipram and poorly sensitive to inhibition by PDE III inhibitors. The PDE IV distribution in canine SR suggests that this form is mostly associated with the FII fraction enriched in sarcolemmal membranes. In contrast, PDE III assessed by its indolidan sensitivity and [3H]LY186126 binding is associated with the microsomal membranes enriched in vesicles derived from T-tubule and junctional SR membranes. Because these membranes are directly involved in controlling excitation-contraction coupling, such PDE location enhances the physiologic relevance to study their implication in regulating cardiac contraction.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Reconstitution and regulation of cation-selective channels from cardiac sarcoplasmic reticulum.

In order to study the conductances of the Sarcoplasmic Reticulum (SR) membrane, microsomal fractions from cardiac SR were isolated by differential and sucrose gradient centrifugations and fused into planar lipid bilayers (PLB) made of phospholipids. Using either KCl or K-gluconate solutions, a large conducting K+ selective channel was characterized by its ohmic conductance (152 pS in 150 mM K+), and the presence of short and long lasting subconducting states. Its open probability Po increased with depolarizing voltages, thus supporting the idea that this channel might allow counter-charge movements of monovalent cations during rapid SR Ca2+ release. An heterogeneity in the kinetic behavior of this channel would suggest that the cardiac SR K+ channels might be regulated by cytoplasmic, luminal, or intra SR membrane biochemical mechanisms. Since the behavior was not modified by variations of [Ca2+] nor by the addition of soluble metabolites such as ATP, GTP, cAMP, cGMP, nor by phosphorylation conditions on both sides of the PLB, a specific interaction with a SR membrane component is postulated. Another cation selective channel was studied in asymmetric Ca2+, Ba2+ or Mg(2+)-HEPES buffers. This channel displayed large conductance values for the above divalent cations 90, 100, and 40 pS, respectively. This channel was activated by microM Ca2+ while its Ca2+ sensitivity was potentiated by millimolar ATP. However Mg2+ and calmodulin modulated its gating behavior. Ca2+ releasing drugs such as caffeine and ryanodine increased its Po. All these features are characteristics of the SR Ca2+ release channel. The ryanodine receptor which has been purified and reconstituted into PLB, may form a cation selective pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Cytosolic and membrane-bound cyclic nucleotide phosphodiesterases from guinea pig cardiac ventricles.

Cyclic nucleotide phosphodiesterase (PDE) activities were characterized in the cytosolic and post-nuclear membrane preparations of guinea pig cardiac ventricles. The cytosolic PDE activities were stimulated 5-fold by calmodulin (CaM) on both substrates (1 microM) and 1.2-fold by cGMP (5 microM) on cAMP hydrolysis. Conversely, in the membrane preparation, CaM only stimulated PDE activities 1.2- to 1.4-fold, but cGMP induced a 3-fold increase of the hydrolysis of cAMP. In both the cytosolic and the membrane preparations, the hydrolysis of cAMP was inhibited by 100 microM of either the PDE III inhibitor SK&F 94120 (27% and 31% respectively) or the PDE IV inhibitor rolipram (14% and 23% respectively). Four peaks were resolved from the cytosolic preparation by chromatography. Peak A and peak B hydrolyzed both cAMP and cGMP and were stimulated respectively by CaM and cGMP. Peak C and peak D selectively hydrolyzed cAMP. Peak C had an apparent Km value for cAMP of 3.3 microM and was inhibited by PDE IV inhibitors. Peak D showed an apparent Km value for cAMP of 0.43 microM and was inhibited by cGMP and by cardiotonic inhibitors of PDE III. Similar potencies of these inhibitors were observed in the membrane preparation. These results suggest that in guinea pig cardiac ventricles: (1) PDE I (CaM-activated) is almost exclusively cytosolic; (2) PDE II (cGMP-stimulated), PDE III (cGMP-inhibited and cardiotonic-sensitive) and PDE IV (rolipram-sensitive) are present in cytosolic and membrane preparations; (3) PDE III and PDE IV differ in their apparent Km values for cAMP. The latter observation could explain the differential effects of PDE III and PDE IV inhibitors in the regulation of cardiac contraction.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1992

Relationship of HLA to schizophrenia not supported in multiplex families.

The role of the human histocompatibility complex (HLA) in the pathogenesis of schizophrenia has been suggested in previous reports. We conducted a genetic study in 33 new families. Our linkage analysis, which used the affected sib-pair method, did not provide evidence for nonrandom assortment. Moreover, the results of an association study using the "haplotype relative risk" method failed to confirm the positive association between HLA A9 and schizophrenia. Taken together, our data did not support any relationship of HLA type to schizophrenia.

Genetic Linkage↗
PubMed1992

Effect of Phloem-Translocated Malate on NO(3) Uptake by Roots of Intact Soybean Plants.

In soybean (Glycine max L. Merr. cv Kingsoy), NO(3) (-) assimilation in leaves resulted in production and transport of malate to roots (B Touraine, N Grignon, C Grignon [1988] Plant Physiol 88: 605-612). This paper examines the significance of this phenomenon for the control of NO(3) (-) uptake by roots. The net NO(3) (-) uptake rate by roots of soybean plants was stimulated by the addition of K-malate to the external solution. It was decreased when phloem translocation was interrupted by hypocotyl girdling, and partially restored by malate addition to the medium, whereas glucose was ineffective. Introduction of K-malate into the transpiration stream using a split root system resulted in an enrichment of the phloem sap translocated back to the roots. This treatment resulted in an increase in both NO(3) (-) uptake and C excretion rates by roots. These results suggest that NO(3) (-) uptake by roots is dependent on the availability of shoot-borne, phloem-translocated malate. Shoot-to-root transport of malate stimulated NO(3) (-) uptake, and excretion of HCO(3) (-) ions was probably released by malate decarboxylation. NO(3) (-) uptake rate increased when the supply of NO(3) (-) to the shoot was increased, and decreased when the activity of nitrate reductase in the shoot was inhibited by WO(4) (2-). We conclude that in situ, NO(3) (-) reduction rate in the shoot may control NO(3) (-) uptake rate in the roots via the translocation rate of malate in the phloem.

Journal Article↗
PubMed1990

Implication of cyclic AMP in the positive inotropic effects of cyclic GMP-inhibited cyclic AMP phosphodiesterase inhibitors on guinea pig isolated left atria.

The present investigation was performed to characterize the positive inotropic actions of inhibitors of the cyclic GMP-inhibited cyclic AMP phosphodiesterase (CGI-PDE) on the electrically driven guinea pig left atria. With forskolin added at a concentration (1 x 10(-8)-3 x 10(-8) M) that in itself produced a 10.7% increase of the response to electrical stimulation, the EC50 value of isoproterenol was slightly but significantly (p less than 0.01) reduced from 1.5 to 0.9 nM without modification of the maximal developed tension (delta Emax). The positive inotropic effects of milrinone, piroximone, and SK&F 94120 were significantly enhanced by forskolin (percentage of increase at 3 x 10(-5) M CGI-PDE inhibitors concentration was milrinone 43, piroximone 154, and SK&F 94120 133). With 8-Br-cyclic GMP added (10(-4) M) that in itself exerted a small but significant negative inotropic effect (-0.12 g), the EC50 value of isoproterenol was significantly (p less than 0.01) increased from 1.5 to 3 nM without modification of the delta Emax value. The positive inotropic effects of CGI-PDE inhibitors were significantly depressed by 8-Br-cyclic GMP (percentage of decrease at 3 x 10(-5) M was milrinone 35, piroximone 63, and SK&F 94120 39). In identical conditions, neither forskolin nor 8-Br-cyclic GMP produced any significant alteration of the positive inotropic effects of elevated external Ca2+ or protoveratrine B. Together these results strongly suggest that the positive inotropic effect of CGI-PDE inhibitors is mediated by cyclic AMP in guinea pig left atria.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Involvement of rolipram-sensitive cyclic AMP phosphodiesterase in the regulation of cardiac contraction.

The involvement of rolipram-sensitive phosphodiesterase (PDE IV) in regulation of cardiac contraction was investigated by studying the effect of selective inhibitors (rolipram, denbufylline, Ro 20-1724) on guinea pig left atria contraction. In contrast to milrinone and SK&F 94120 (inhibitors of the cyclic GMP-inhibited PDE, PDE III), (+/-)-rolipram and denbufylline (0.1-30 microM) did not produce any positive inotropic effect in normal (2.5 mM) or elevated (3-3.2 mM) external CaCl2 concentration. In these conditions, Ro 20-1724 produced only a slight but significant increase of contraction over control levels. In the presence of forskolin (an adenylate cyclase activator) or SK&F 94120 (a PDE III inhibitor), which produced an increase of the response to electrical stimulation of approximately 10%, (+/-)-rolipram, denbufylline, and Ro 20-1724 all exerted concentration-dependent positive inotropic effects (mean EC50 values were 20, 25, and 125 nM, respectively, in the presence of forskolin). Rolipram exhibited stereospecificity: the (-)-enantiomer was 10 times more potent than the (+)-enantiomer. Neither preincubation of the atria with atenolol nor pretreatment of the guinea pigs with reserpine significantly modified the effect of PDE IV inhibitors obtained in the presence of forskolin. These data show that in the presence of cyclic AMP-dependent positive inotropic agents, PDE IV inhibitors exert a positive inotropic effect which probably does not involve enhanced catecholamine release from sympathetic nerve endings. This suggests that PDE IV may play a role in regulation of cardiac contraction in physiologic conditions in which the sympathetic outflow produces a stimulation of adenylate cyclase in cardiac cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

The psychiatric hospitalization of children: an overview.

This paper reviews significant outcome studies regarding the hospitalization of latency-age children and examines pertinent admission criteria. Essential diagnostic and therapeutic components, including milieu therapy, individual therapy, family work, pharmacotherapy and school are discussed. The future role of psychiatric hospitalization of children is examined.

Child↗
PubMed1988

Estradiol involvement in the luteolytic action of LH during the estrous cycle in the rat.

The study was undertaken to examine LH, prolactin (Prl) and estradiol involvement in the control of corpus luteum function during 4-day cycle in the female rat. A potent LHRH antagonist (Antag) and bromocriptine (BRC) were used to induce LH and Prl deprivation in 4-day cyclic rats. Both drugs were administered after the occurrence of LH and Prl release on the afternoon of proestrus. Blood progesterone (P) concentration on diestrus 1 at 24:00 hr was similar in Antag, Antag + BRC and BRC-treated animals and did not differ from P values in control females. It was then concluded that neither LH nor Prl were necessary for the corpus luteum to achieve its stage of maximal activity during the night from diestrus 1 to diestrus 2. By contrast higher P values were observed on diestrus 2 at 12:00 hr in Antag-treated rats than in those given Antag + BRC, BRC or in the controls. When given on diestrus 1 evening estradiol benzoate completely prevented this effect of Antag to occur in LH and Prl deprived females. These results allow to hypothesize that LH exerts luteolytic effects during the diestrous period of the cycle and also suggest a possible involvement of estradiol in the regression phase of the corpus luteum.

Animals↗
PubMed1986

Dopaminergic and noradrenergic sympathetic nerves of the dog have different DOPA decarboxylase activities.

We have compared the pattern of neural catecholamine fluorescence with that of immunoreactivity for the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC) in dog atrium, which is innervated by noradrenergic nerves, and in dog kidney, which is thought to be supplied by dopaminergic nerves as well. In both tissues the distribution of nerves containing catecholamine fluorescence was similar to that of nerves exhibiting TH-like immunoreactivity. By contrast, DDC-like immunoreactivity was present in some (but not all) of the nerves associated with the intrarenal blood vessels, but was not detectable in any atrial nerves. High DDC activity provides further confirmation of the existence of sympathetic dopaminergic neurons supplying the kidney.

Animals↗