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J Stutzmann

Publications and source records attributed to J Stutzmann.

At least 19 recordsLinked to original sources

Adhesion complexes implicated in intestinal epithelial cell-matrix interactions.

This article review summarizes data on cell-substratum adhesion complexes involved in the regulation of cellular functions in the intestine. We first focus on the molecular composition of the two main adhesion structures-the beta1 integrin-adhesion complex and the hemidesmosome-found in vivo and in two human intestinal cell lines. We also report the key findings on the cellular behavior and response to the extracellular matrix that involve integrins, the main transmembrane anchors of these complexes. How the dynamics of cell/extracellular matrix interactions contribute to cell migration, proliferation, differentiation, and tumorigenicity is discussed in the light of the data provided by the human intestinal cells.

Caco-2 Cells↗

Regulation of the type II hemidesmosomal plaque assembly in intestinal epithelial cells.

Hemidesmosomes (HDs) are cellular junctions that anchor epithelial cells to the extracellular matrix (ECM) and are associated morphologically with the cytoskeleton. Hemidesmosomal molecular components include two proteins involved in linking intermediate filaments, HD1/plectin and BP230, and two transmembrane proteins, BP180 and the alpha6beta4 integrin, a laminin receptor. In cells lacking BP230 and BP180, HD1/plectin still associates with alpha6beta4 integrin, forming HD-like structures, called type II HDs. In the present study, we used an intestinal epithelial cell line that expresses HD1/plectin and the alpha6beta4 integrin to investigate the regulation of assembly of these proteins in type II HDs. These compounds were found to be clustered at sites of cell-ECM contact and their polarized localization was influenced by either cell confluency or extracellular matrix deposition. Conventional and immunoelectron microscopy showed that HD1/plectin and the beta4 integrin subunit are colocalized in an adhesion structure. Using cytoskeleton-disrupting drugs and confocal microscopy, we demonstrated that type II HDs are made up of numerous individual plaques whose assembly into a cluster requires actin filaments, but not microtubules.

Actin Cytoskeleton↗

Role of imidazoline receptors in cardiovascular regulation.

The involvement of nonadrenergic imidazoline specific receptors in the central control of the vasomotor tone and in the mechanism of action of drugs bearing an imidazoline structure, or analogs, is now well documented. Imidazoline-specific binding sites were found in many tissues and species. Moreover, until now, it is only in the brainstem that such binding sites are associated with a function: the hypotensive effect of imidazoline-like drugs. Rilmenidine, which is an oxazoline structurally related to the reference imidazolines, exerts a central hypotensive effect of central origin involving imidazoline receptors. The selectivity of rilmenidine for the imidazoline receptors compared to alpha 2-adrenergic receptors could explain the low incidence of sedative side effects observed with this antihypertensive drug. A specific anti-imidazoline radioimmunoassay allowed us to detect the presence of an immunoreactive imidazoline-like substance in human sera. High levels of this immunoreactive substance are associated with high blood pressure in 20-30% of the hypertensive patients. This observation indicates that high levels of this immunoreactive substance in the serum can be associated with some kinds of primary hypertension. The cause-and-effect relation between these 2 phenomena has not yet been determined. This substance is in process of purification; it could be a candidate to be an endogenous ligand of the imidazoline receptors.

Animals↗

Human brain imidazoline receptors: further characterization with [3H]clonidine.

The aim of the present study was to further characterize [3H]clonidine binding in the ventrolateral medulla of the human brainstem, the region involved in the vasodepressor effect of imidazoline drugs of the clonidine type. Under basal conditions, [3H]clonidine can bind both to the imidazoline receptors and to the alpha-adrenoceptors. The latter represent only a small part of the total [3H]clonidine binding with a Bmax of 61 +/- 13 fmol/mg proteins and a KD of 4.9 +/- 2.2 nM. Most of the binding was associated with imidazoline receptors with a KD of 67 +/- 13 nM and a Bmax of 677 +/- 136 fmol/mg protein. alpha-Adrenoceptor binding of [3H]clonidine could be completely prevented when membranes were either treated during preparation with the aIkylating agent phenoxybenzamine or incubated in the presence of 30 microM (-)-noradrenaline or in the presence of the non-hydrolysable analogue of GTP, guanylyl imidodiphosphate (Gpp(NH)p). When the alpha-adrenoceptors binding was prevented, we demonstrated the insensitivity of [3H]clonidine binding to Gpp(NH)p and showed that the competition between clonidine and idazoxan for imidazoline receptors was insensitive to Gpp(NH)p suggesting that imidazoline receptors are not G protein coupled receptors. The specificity of [3H]cloniding binding to imidazoline receptors in the human ventrolateral medulla indicates that these receptors are different from imidazole receptors as defined with p-aminoclonidine in the bovine brainstem.

Binding, Competitive↗

Characterization of imidazoline binding protein(s) solubilized from human brainstem: studies with [3H]idazoxan and [3H]clonidine.

Imidazoline binding sites from the human brainstem were solubilized with 3-[(3-cholamido-propyl)-dimethylammonio]-1-propane-sulfonate (CHAPS). [3H]idazoxan and [3H]clonidine were used as ligands to characterize the solubilized binding sites. In both the soluble and membrane fractions, [3H]idazoxan binding was saturable, stereoselective, sensitive to imidazolines and insensitive to (-)norepinephrine and to amiloride. The affinities of [3H]idazoxan for the soluble and membrane sites were similar (KD = 25 +/- 11 nM and 20 +/- 3 nM). In both soluble and membrane fractions, the alpha 2-adrenoceptor binding being masked with (-)norepinephrine, [3H]clonidine bound to a low affinity site which was insensitive to (-)norepinephrine and which exhibited the same selectivity for various drugs as the [3H]idazoxan binding site. alpha 2-adrenoceptor binding was present in the membrane and the soluble fractions although it was difficult to detect in the soluble fraction because of inhibition of [3H]rauwolscine binding by the CHAPS detergent.

Binding Sites↗

Reaction of the pterygomaxillary fissure and the condylar cartilage to intermaxillary Class III magnetic mechanics.

The skeletal reaction to Class III intermaxillary magnetic mechanics was previously found to affect two target areas, the pterygomaxillary fissure (PMF) and the condylar cartilage. The objectives of this study were to analyze, radiographically and histologically, the response of these tissues to Class III intermaxillary functional orthopedic magnetic appliance (FOMA III), and to postulate possible models of their dichotomous biomechanism. Nine Macaca fascicularis monkeys received periodic administration of vital bone procion dye and were treated for 4 months with FOMA III (6 subjects) and sham appliance (3 subjects). The PMF (the target area of the midfacial complex) demonstrated a decreased skeletal reaction in inferosuperior and lateromedial directions. Cephalometrically, the lowermost PMF point was displaced inferiorly 1.98 +/- 1.74 mm and 0.42 +/- 0.38 mm and anteriorly 1.42 +/- 0.96 mm and 0.58 +/- 0.38 mm in the treated and control groups, respectively. The displacement of the uppermost PMF point, compared with the lowermost point, was three to five times lower. Histologically, two modes of response were found; first, a sutural response (disarticulation and osteogenesis) of the palatomaxillary and pterygopalatine sutures, which was distinctive of the lateral PMF aspect, and second, a dentosutural response, which was characteristic of the medial PMF aspect (bony microfractures between the third molar germ and the maxillary tuberosity in conjunction with mild sutural response). In the mandible, a discrepancy was found between the histologic and the cephalometric findings. Radiographically, mandibular length was unaffected after 4 months of treatment, and the distance condylion-pogonion was equally increased in the treated (0.75 +/- 0.78 mm) and the control animals (0.77 +/- 0.32 mm). Histologically, however, the condylar cartilage demonstrated increased osteoclastic activity at the zone of endochondral ossification and a decreased apposition rate at the adjacent bony trabeculae. Conceivably, the two target areas (PMF sutures versus condylar cartilage) demonstrate two diverse time-related responses that are either unrelated or interrelated to each other. An unrelated tissue response suggests that tissue stimulation (sutural) is always superior to tissue suppression (condylar). Another possible unrelated tissue reaction implies diverse response velocity (high sutural, low condylar). An interrelated mechanism suggests that an applied force will dissipate initially at the less resistant target area (sutures), and will subsequently affect the more resistant target area (condyle) once the sutural resistance exceeds a certain threshold. The fact that no pathologic change was found in the condylar cartilage encourages a long-term use of the FOMA III appliance, initiating treatment at an early skeletal age.

Animals↗

Medullary hypotensive effect of endothelin1 in anaesthetized animals.

In anaesthetized animals, systemic injection of ET1 at doses from 3 to 100 ng.kg-1 provoked only a transient hypotensive effect. At 300 ng.kg-1 we observed the classical biphasic effect, consisting of a transient lowering of the arterial pressure followed by a long-lasting hypertensive effect. Direct injection of the peptide into the vertebral artery of anaesthetized animals only affected arterial pressure (AP) when the blood-brain barrier was permeabilised. Under these conditions, a dose-dependent decrease in AP was observed, which was not associated with a significant effect on the heart rate. Micro-injections of the peptide in the medullary nucleus reticularis lateralis area (NRL), a medullary vasopressive centre, at doses of 30 to 60 ng.kg-1 led to a significant reduction in mean arterial pressure (MAP) (17 +/- 4% and 36.5 +/- 6%) respectively without a significant change in heart rate. These effects lasted less than 2 hours. These results suggest a possible role of ET1 as a neuromodulator involved in the central regulation of vasomotor tone, in the NRL region.

Anesthesia↗

Relevance of the use of [3H]-clonidine to identify imidazoline receptors in the rabbit brainstem.

1. [3H]-clonidine binding was investigated in membranes isolated from the ventral medulla oblongata of the rabbit, where clonidine produced a hypotensive effect which was not mediated by adrenoceptors. [3H]-clonidine specific binding, as defined by the difference between the binding of [3H]-clonidine in the presence and in the absence of 10 microM cirazoline, occurred at two sites: a high affinity site with a KD = 2.9 +/- 0.7 nM and a Bmax of 40 +/- 8 fmol mg-1 protein and a low affinity site with a KD = 18.2 +/- 0.4 nM and a Bmax of 66 +/- 14 fmol mg-1 protein. 2. The high affinity sites being catecholamine-sensitive were identified as alpha 2-adrenoceptors. The low affinity binding of [3H]-clonidine was insensitive to catecholamines, as well as to other alpha 2-adrenoceptor specific probes, and could be inhibited with high affinity only by compounds which lowered blood pressure when directly injected in the nucleus reticularis lateralis of the ventral brainstem, or by antagonists. 3. It was concluded that in the ventral medulla of the rabbit, [3H]-clonidine labelled alpha 2-adrenoceptors and imidazoline receptors (IRs). Only the latter were related to the hypotensive effects of clonidine and rilmenidine directly injected into the rostroventrolateral medulla oblongata (RVLM) of the rabbit. The methodological problems regarding the study of IRs with [3H]-clonidine are discussed.

Animals↗

Imidazoline receptors. A new concept in central regulation of the arterial blood pressure.

Clonidine-like antihypertensive substances bind to nonadrenergic imidazoline specific sites within the nucleus reticularis lateralis (NRL), their medullary privileged site of action. Rilmenidine, a new central antihypertensive agent, was tested in the anesthetized rabbit. For the same hypotensive effect, cumulative doses given intracisternally proved 50 times more active than of those given systemically. Idazoxan, an alpha 2-adrenergic antagonist structurally related to the imidazolines, given centrally as pretreatment proved more potent in preventing the hypotensive effects than the same molar dose of yohimbine. When injected within the NRL area of the anesthetized rabbit, rilmenidine, like clonidine, always exhibited a hypotensive effect. The influence of clonidine and rilmenidine upon the NRL noradrenergic neurons involved in the blood pressure regulation, and upon those of the locus coeruleus (LC) involved in the sedative effect was studied by differential voltammetry. It was observed that rilmenidine was two times more selective than clonidine in inhibiting the NRL, as opposed to LC, neuronal activity. In addition, binding experiments of tritiated clonidine to human cortical and NRL membrane preparations showed that rilmenidine, as compared to clonidine, has a two to three times higher selectivity for the imidazoline receptors. In conclusion, we are now able to discriminate between the mechanism of the hypotensive effect of imidazoline-like drugs and that of their sedative action. Rilmenidine is the first example of an hypotensive drug more selective for imidazolin preferring receptors than for classical alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗

Modus operandi of Planas' appliance.

Planas' approach to the management of a distocclusion, as applied by Simoes, is analyzed physiologically by taking into account the Petrovic-Stutzmann's cybernetic vision of facial growth. This scientifically based theorization further strengthens the clinical validity of this orthodontic ideology and procedure. The clinician, the orthodontist, the functional orthopedist or the functional orthodontist are fundamentally dependent on their knowledge about biophysics, biochemistry and mainly physiology. It is important then that they be acquainted with fundamental concepts of basic sciences as applicable to the specialty. In planning the treatment of a malocclusion, it is necessary to select the appliance or the series of them for sequential use in the correction of a intermaxillary malrelation. It is also useful to be able to predict the response to each appliance. In this case it must be considered the input (appliance in the mouth) designed to produce either displacements of the teeth or other modifications within the dentofacial complex and the output (appliance effect). According to Petrovic and Stutzmann there are 6 tissue level growth categories. Previous investigations using Frankel appliance, LSU Activator, Bionator, Chin Cup and Begg techniques, have shown that when going from the growing category number 1 to number 6 it becomes easier to stimulate the growth rate and amount of the condylar cartilage and of the posterior border of the ramus and it becomes more difficult to restrain their growth rate and amount. In other words we have also to test clinically the effectiveness of the Planas Appliance by taking into account the inter-individual variation in the tissue level responsiveness to it. (Fig. 1-4).(ABSTRACT TRUNCATED AT 250 WORDS)

Activator Appliances↗

Effects on the rat mandible of a chincup-type appliance and of partial or complete immobilization.

Sixty 20-day-old male rats were divided into 4 groups: controls (group 1), partly immobilized mandible with a chincup-type appliance (group 2) and completely immobilized mandible without (group 3) or with (group 4) a chincup-type appliance. After 4 weeks the rats were killed and 3 parameters were measured: number of 3H-thymidine labelled cells in the condylar cartilage. "Stutzmann's angle" and length of the mandible. The growth rate of the condylar cartilage and the lengthening of the mandible were both smaller than in the controls. The chincup treatment was much more efficient when the mandible was completely immobilized than when it was only partly immobilized.

Animals↗

Ultradian mitotic rhythms in culture of human sarcomatous bone cells originating from the patient before and after chemotherapy.

Bone sarcomatous cells derived from human malignant tumors were cultured. The mitotic index was recorded for 39 hr. When the cultured cells originated from patients with cancer disease before any chemotherapy, ultradian mitotic rhythms of a 6-9-hr period were detected, but in many cases only after a sensitive statistical analysis was performed. When the cultured cells originated from cancer patients undergoing chemotherapy, the mitotic index was decreased, and the amplitudes of the 6-9-hr component oscillations of the mitotic index were highly significantly increased. Damping and fading out of an ultradian mitotic rhythmicity was a bad prognostic portent in bone cancer. With reference to chemotherapy, the restored and amplified ultradian rhythmicity disclosed an appreciable antitumor effect and better survival prospects for the patient.

Bone Neoplasms↗

[Surgical treatment of hypoplasia of the ascending ramus of the mandible in children using an autologous osteochondral costal graft].

To lengthen the child's mandibular ramus, we use, since 1977, an autologous osteochondral rib graft fixed to the posterior margin of the ramus. Experimental studies show that this graft has a growth potential, the osteochondral junction responds to the biomechanical forces in a similar way to the mandibular condyle. Surgical treatment allows an immediate restitution of the morphology, normal masticatory function and good buccal opening. The interposition of cartilage prevents recurrence. The growth potential of the graft due to osteochondral junction activity, allows surgery to be performed in childhood, without requiring a further surgical operation several years later. This constitutes an optimistic prospect for the future and the good results obtained with 8 patients are analyzed.

Bone Lengthening↗