[Algorithm for securing an unexpected difficult airway : User analysis on a simulator]. / Algorithmus zur Sicherung des unerwartet schwierigen Atemwegs : Eine Anwenderanalyse am Simulator.

BACKGROUND: Critical incidents in difficult airway management are still a main contributory factor for perioperative morbidity and mortality. Many national associations have developed algorithms for management of these time critical events. For implementation of these algorithms the provision of technical requirements and procedure-related training are essential. Severe airway incidents are rare events and clinical experience of the individual operators is limited; therefore, simulation is an adequate instrument for training and evaluating difficult airway algorithms. OBJECTIVE: The aim of this observational study was to evaluate the application of the institutional difficult airway algorithm among anesthetists. MATERIAL AND METHODS: After ethics committee approval, anesthetists were observed while treating a "cannot intubate" (CI) and a "cannot intubate, cannot ventilate" (CICV) situation in the institutional simulation center. As leader of a supportive team the participants had to deal with an unexpected difficult airway after induction of anesthesia in a patient simulator. The following data were recorded: sequence of the applied airway instruments, time to ventilation after establishing a secured airway using any instrument in the CI situation and time to ventilation via cricothyrotomy in the CICV situation. Conformity to the algorithm was defined by the sequence of the applied instruments. Analysis comprised conformity to the algorithm, non-parametric tests for time to ventilation and differences between junior and senior anesthetists. RESULTS: Out of 50 participants 45 were analyzed in the CI situation. In this situation 93% of the participants acted in conformity with the algorithm. In 62% the airway was secured by flexible intubation endoscopy, in 38% with another device. Data from 46 participants were analyzed in the CICV situation. In this situation 91% acted in conformity with the algorithm. The last device used prior to the decision for cricothyrotomy was flexible intubation endoscopy in 39%, a laryngeal mask in 22% and other instruments in 39%. Of the 50 participants 38 had already been institutionally trained in difficult airway management during the previous 2 years. For cricothyrotomy the participants needed a median time of 63 s and there was no difference between junior and senior anesthetists (p = 0.46). The cricothyrotomy was performed faster using a surgical approach than a transtracheal puncture approach using a Melker emergency cricothyrotomy set (52 s vs. 73 s, p = 0.014). CONCLUSION: The conformity to the algorithm of over 90% indicates a good training level of the participants concerning the difficult airway algorithm. In the observed sample flexible intubation endoscopy tended to be of high significance even in the unanticipated difficult airway. Cricothyrotomy was performed faster surgically than by the use of the transtracheal puncture approach, while no differences between junior and senior anesthetists were observed. For the successful management of an unexpected difficult airway, specific training of these special and rare events is crucial. A standardized provision of special airway instruments stored in a special trolley and frequent application of this trolley in the clinical routine is recommended.

Semiautomated quantitative image analysis of glomerular immunohistochemistry markers desmin, vimentin, podocin, synaptopodin and WT-1 in acute and chronic rat kidney disease models.

Five different glomerular immunohistochemistry markers were evaluated and compared in four different acute and chronic rat kidney disease models. Progression of glomerular or podocyte damage was shown in the puromycin aminonucleoside nephrosis (PAN) and Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model. Progression and prevention of glomerular damage was demonstrated in the Zucker diabetic fatty (ZDF) and Dahl salt-sensitive (Dahl SS) rat. Immunohistochemistry was performed for desmin, vimentin, podocin, synaptopodin and Wilms tumor protein-1 (WT-1), and evaluation of glomerular immunohistochemistry markers was done by semiautomated quantitative image analysis. We found desmin and WT-1 as the most sensitive markers for podocyte damage in both acute and chronic glomerular damage followed by vimentin, podocin and synaptopodin. We were able to demonstrate that early podocyte damage as shown by increased desmin and vimentin staining together with either a phenotypic podocyte change or podocyte loss (reduced numbers of WT-1-stained podocytes) drives the progression of glomerular damage. This is followed by a reduction in podocyte-specific proteins such as podocin and synaptopodin. Our report describes the different sensitivity of glomerular or podocyte markers and gives future guidance for the selection of the most sensitive markers for efficacy testing of new drugs as well as for the selection of tissue-based toxicity markers for glomerular or podocyte injury. In addition to functional clinical chemistry markers, desmin and WT-1 immunohistochemistry offers reliable and valuable data on the morphologic state of podocytes.

Acute sleep deprivation delays the glucagon-like peptide 1 peak response to breakfast in healthy men.

OBJECTIVE: Previous experiments have demonstrated that acute sleep loss impairs glucose homeostasis and increases food intake in humans. The incretin hormone glucagon-like peptide 1 (GLP-1) enhances postprandial insulin secretion and promotes satiety. Hypothesizing that the detrimental metabolic effects of sleep curtailment imply alterations in GLP-1 signaling, we investigated 24-h serum total GLP-1 concentrations during total sleep deprivation (TSD) and a normal sleep/wake cycle (comprising ∼8 h of sleep) in 12 healthy young men. METHODS: Sessions started at 1800 h, and subjects were provided with standardized meals. Assessments of serum GLP-1 took place in 1.5- to 3-h intervals, focusing on the response to breakfast intake (3.8 MJ). RESULTS: Across conditions, 24-h concentration profiles of GLP-1 were characterized by the expected postprandial increases (P<0.001). Although there were no differences in magnitude between conditions (P>0.11), the postprandial GLP-1 peak response to breakfast intake was delayed by ∼90 min following sleep loss in comparison with regular sleep (P<0.02). CONCLUSIONS: RESULTS indicate that acute TSD exerts a mild, but discernible effect on the postprandial dynamics of circulating GLP-1 concentrations in healthy men.

Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism.

In recent years, the central nervous system (CNS) has emerged as a principal site of insulin action. This notion is supported by studies in animals relying on intracerebroventricular insulin infusion and by experiments in humans that make use of the intranasal pathway of insulin administration to the brain. Employing neurobehavioural and metabolic measurements as well as functional imaging techniques, these studies have provided insight into a broad range of central and peripheral effects of brain insulin. The present review focuses on CNS effects of insulin administered via the intranasal route on cognition, in particular memory function, and whole-body energy homeostasis including glucose metabolism. Furthermore, evidence is reviewed that suggests a pathophysiological role of impaired brain insulin signaling in obesity and type 2 diabetes, which are hallmarked by peripheral and possibly central nervous insulin resistance, as well as in conditions such as Alzheimer's disease where CNS insulin resistance might contribute to cognitive dysfunction.

[Outpatient surgery: an unstoppable evolution]. / Chirurgie ambulatoire: une voie incontournable.

The trend is to definitely shorten hospital stays. It follows in the footsteps of a broader range of surgeries that can be managed in an ambulatory care setting. The expected benefits are: a reduction in costs, a shorter preoperative delay, a shorter absence for the work place and a lessened risk of hospital-borne infections. A multidisciplinary approach is essential for the success of such a program. Surgeons, anaesthetists and nursing staff must be prepared to modify and adapt their skills. The criterion of success for such an endeavour is a low level of readmissions and hospitalisations. If day surgery tends to keep the patient away for the hospital settings, it certainly places him in the centre of his medical management.

[Trends in the spread of pandemic influenza A(H1N1) swl in the Far East in 2009].

The paper describes the trend in the spread of pandemic influenza A(H1N1) swl virus in the Far East, which started in this region 2-3 months later than that in the European part of Russia. By mid-October seasonal epidemic influenza was practically displaced by pandemic one.

Late intestinal fistula formation after incisional hernia using intraperitoneal mesh.

Enteric fistulas are a rare but serious complication following the repair of an incisional hernia using a prosthesis. We report the case of a 52-year-old man who developed an enterocolocutaneus fistula after incisional hernia repair with intra-abdominal polyester mesh. This case shows that one may want to avoid placing the parietal prostheses in direct contact with intestinal loops.

Leptin secretion and negative autocrine crosstalk with insulin in brown adipocytes.

Leptin is an important adipocytokine whose main regulative effects on energy metabolism are exerted via activation of signalling pathways in the central nervous system. Another important regulator of energy homeostasis is insulin. The role of direct autocrine leptin effects on adipose tissue and crosstalk with insulin, in particular in the thermogenically active brown adipose tissue, remains unclear. In the present study, we have investigated leptin secretion and interaction with insulin in highly insulin-responsive immortalised mouse brown adipocytes. Leptin was secreted in a differentiation-dependent manner, and acute leptin treatment of mature adipocytes dose- and time-dependently stimulated phosphorylation of STAT3 and MAP kinase. Interestingly, acute pretreatment of fully differentiated brown adipocytes with leptin (100 nM) significantly diminished insulin-induced glucose uptake by approximately 25%. This inhibitory effect was time-dependent and maximal after 60 min of leptin prestimulation. Furthermore, it correlated with a 35% reduction in insulin-stimulated insulin receptor kinase activity after acute leptin pretreatment. Insulin-induced insulin receptor substrate-1 tyrosine phosphorylation and binding to the regulatory subunit p85 of phosphatidylinositol 3-kinase (PI 3-kinase) were diminished by approximately 60% and 40%, respectively. Taken together, this study has demonstrated strong differentiation-dependent leptin secretion in brown adipocytes and PI 3-kinase-mediated negative autocrine effects of this hormone on insulin action. Direct peripheral leptin-insulin crosstalk may play an important role in the regulation of energy homeostasis.

Direct effects of ciliary neurotrophic factor on brown adipocytes: evidence for a role in peripheral regulation of energy homeostasis.

Ciliary neurotrophic factor (CNTF) plays an important role in regulating neuronal growth. Recently, central anorexigenic effects of this cytokine have been characterized. However, peripheral effects on tissues that actively contribute to the regulation of energy homeostasis have not been described. Here, we report direct potent and selective effects of CNTF on growth factor and metabolic signalling intermediates in mouse brown adipocytes. CNTF stimulates STAT3, MAP kinase, Akt, and p70 S6 kinase. We find that, next to mediating Akt and p70 S6 kinase activation, both phosphatidylinositol 3-kinase and protein kinase C are separately acting, main intermediates for inducing mitogen-activated protein (MAP) kinase activation. On a functional level, CNTF enhances beta3-adrenergic induction of uncoupling protein-1. Thus, these results demonstrate direct effects of CNTF on adipose tissue signalling and metabolism and suggest a novel role for this cytokine in the peripheral regulation of energy homeostasis.

Oligoneuronal hypoganglionosis in patients with idiopathic slow-transit constipation.

PURPOSE: Several alterations of the enteric nervous system have been described as an underlying neuropathologic correlate in patients with idiopathic slow-transit constipation. To obtain comprehensive data on the structural components of the intramural nerve plexus, the colonic enteric nervous system was investigated in patients with slow-transit constipation and compared with controls by means of a quantitative morphometric analysis. METHODS: Resected specimens were obtained from ten patients with slow-transit constipation and ten controls (nonobstructive neoplasias) and processed for immunohistochemistry with the neuronal marker Protein Gene Product 9.5. The morphometric analysis was performed separately for the myenteric plexus and submucous plexus compartments and included the quantification of ganglia, neurons, glial cells, and nerve fibers. RESULTS: In patients with slow-transit constipation, the total ganglionic area and neuronal number per intestinal length as well as the mean neuron count per ganglion were significantly decreased within the myenteric plexus and external submucous plexus. The ratio of glial cells to neurons was significantly increased in myenteric ganglia but not in submucous ganglia. On statistical analysis, the histopathologic criteria (submucous giant ganglia and hypertrophic nerve fibers) of intestinal neuronal dysplasia previously described in patients with slow-transit constipation were not completely fulfilled. CONCLUSION: The colonic motor dysfunction in slow-transit constipation is associated with quantitative alterations of the enteric nervous system. The underlying defect is characterized morphologically by oligoneuronal hypoganglionosis. Because the neuropathologic alterations primarily affect the myenteric plexus and external submucous plexus, superficial submucous biopsies are not suitable to detect these innervational disorders.

Direct peripheral effects of ghrelin include suppression of adiponectin expression.

The stomach-derived peptide, ghrelin, has recently been discovered as an important regulator of energy homeostasis. Central nervous system pathways involving stimulation of hypothalamic neuropeptides play a prominent role in mediating ghrelin's orexigenic effects. However, potential direct peripheral effects remain poorly understood. Using a brown adipocyte model, we tested ghrelin-mediated influences on adipose tissue. Chronic ghrelin stimulation of differentiating adipocytes did not affect the pattern or extent of fat accumulation. Furthermore, insulin-induced glucose uptake as a hallmark of adipocyte function was not altered by ghrelin pre-treatment. However, acute ghrelin treatment resulted in a significant time-dependent increase in p44/42 mitogen-activated protein kinase phosphorylation. There was no stimulation of phosphatidylinositol 3-kinase, JAK/STAT, or stress kinase signaling pathways. Furthermore, ghrelin did not significantly alter gene expression of the thermogenic uncoupling protein-1. By contrast, expression of the novel adipokine adiponectin, which has been implicated in the pathogenesis of insulin resistance and obesity, was strongly impaired. This inhibition occurred acutely, and was sustained for several hours. In summary, our data provide evidence for selective effects of ghrelin on adipocyte signaling and function and thus propose a role for adipose tissue as a novel mediator of ghrelin's effects on energy balance and glucose homeostasis.

FcgammaRIIB-mediated inhibition of T-cell receptor signal transduction involves the phosphorylation of SH2-containing inositol 5-phosphatase (SHIP), dephosphorylation of the linker of activated T-cells (LAT) and inhibition of calcium mobilization.

The low-affinity receptor for immunoglobulin G, FcgammaRIIB, is expressed on most B-cells and on immature and activated mature T-cells. Co-aggregation of FcgammaRIIB with the B-cell antigen receptor (BCR) leads to attenuation of BCR-induced blastogenesis and cell proliferation via inhibition of p21(ras), phosphatidylinositol 3-kinase (PI3-K) and phospholipase Cgamma (PLCgamma) activation. These effects are mediated, at least in part, by the recruitment of SH2-containing protein tyrosine phosphatase-1 (SHP-1) and -2 (SHP-2) and SH2-containing inositol 5-phosphatase (SHIP). In this report, we demonstrate that FcgammaRIIB co-aggregation with the T-cell antigen receptor (TCR), which may occur when T-cells recognize antibody-coated target cells, leads to inhibition of TCR-induced phosphorylation of the linker of activated T-cells (LAT). When phosphorylated, LAT functions as an adapter molecule and recruits PI3-K. Additionally, we demonstrate that PI3-K is required for TCR-induced Ca(2+) mobilization. Together, these data suggest that FcgammaRIIB may inhibit TCR-mediated Ca(2+) mobilization, in part via inhibition of LAT phosphorylation and subsequent inhibition of PI3-K activation. A similar mechanism has been described in B-cells, where FcgammaRIIB co-aggregation with the BCR leads to inhibition of PI3-K activity via dephosphorylation of CD19. It is likely that, in both cell types, levels of PtdIns(3,4,5)P(3) are additionally modulated via the enzymic activity of SHIP.

Fc gamma RIIB as a potential molecular target for intravenous gamma globulin therapy.

The ability of the immune system to respond appropriately to foreign antigen is dependent on a delicate balance of activating and inhibitory signals. Recently, the role of cell surface inhibitory receptors in attenuating immune responses, thereby preventing pathologic conditions including autoimmunity and atopy, has been recognized. It is postulated that the beneficial effects of intravenous gamma globulin in the treatment of immune disorders may be attributable, at least in part, to engagement of Fc gamma RIIB, a member of the recently described family of immune inhibitory receptors. Recent genetic and biochemical studies have identified the SH2 domain-containing inositol 5-phosphatase (SHIP) as a critical effector in Fc gamma RIIB inhibitory signaling. This review summarizes recent work from our laboratory and others aimed to define the mechanism(s) by which Fc gamma RIIB and its effector, SHIP, inhibit immune responses. Elucidation of these mechanisms may lead to the development of therapeutic strategies for the treatment of autoimmune and inflammatory pathologies that specifically target Fc gamma RIIB or its effector(s).

Accuracy of two-dimensional electrophoresis for target discovery in human colorectal cancer.

Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is increasingly used for target discovery in human disease to complement genomic studies. We have assessed the possibilities and limits of 2-D PAGE applied to human colorectal cancer. Up to 10(8) epithelial cells were purified from paired normal and pathological biopsies using Ber-EP4 coated magnetic beads, allowing the elimination of cellular and fluid contaminations. The mean coefficient of variation (CVAR) of repeated 2-D PAGE analysis with silver staining was lying between 20 and 28%. However, only 47% (interrun) to 76% (intrarun) of spots could be matched within a triplicate experiment. Interindividual phenotypic variability was high. Intratumoral phenotypic variability was not found to be significant. When method and tumor variability were added, 90% of CVAR were inferior to 48%. Thus, two-fold up- or down-regulation of protein expression reveals biological significance. Serial paired comparison of 923 proteins in 10 patients showed highly reproducible differences between normal and cancer tissues. Under well defined experimental conditions and after the high variability of the technique has been considered, 2-D PAGE parallel analysis of paired colorectal samples allows patient-specific tumor profiling.

Activating and inhibitory signaling in mast cells: new opportunities for therapeutic intervention?

Immune responses are tightly controlled by the activities of both activating and inhibitory signals. At the cellular level, these signals are generated through engagement of membrane-associated receptors and coreceptors. The high-affinity IgE receptor FcepsilonRI is expressed on mast cells and basophils and, on cross-linking by multivalent antigen (allergen), stimulates the release of inflammatory mediators that induce acute allergic responses. Activation signals mediated by a variety of immune receptors (eg, B-cell receptor, T-cell receptor, and FcepsilonRI) are subject to negative regulation by a growing family of structurally and functionally related inhibitory receptors. Recent studies indicate that mast cells express multiple inhibitory receptors that may regulate FcepsilonRI-induced mast cell activation through similar mechanisms. The ability of inhibitory receptors to attenuate IgE-mediated allergic responses implicates them as potential targets for therapeutic intervention in the treatment of atopic disease. Indeed, coaggregation of activating and inhibitory receptors has been suggested as one possible mechanism to explain the beneficial effects of specific immunotherapy in the treatment of allergy. In this review we summarize the current knowledge of inhibitory receptors expressed in mast cells and the mechanisms through which they regulate mast cell function.

[Disorders of intestinal innervation as a possible cause for chronic constipation]. / Intestinale Innervationsstörungen als mögliche Ursache der chronischen Obstipation.

The gastrointestinal tract contains the largest amount of nerve cells apart from the central nervous system constituting together with glial cells the enteric nervous system (ENS). The morphology of the ENS is characterized by intramurally located ganglionated and non-ganglionated plexus of different structure. The diversity of neurotransmitters synthesized by the different nerve cell types as well as the complex neuronal circuits establish the basis for the mediation of a coordinated intestinal motility. Subsequently abnormalities of the ENS may cause severe constipation. The most acknowledged intestinal innervation disorder represents aganglionosis (Hirschsprung's disease) characterized by the absence of intramural nerve cells and the hypertrophy of nerve fiber bundles within the affected intestinal segment. Non-aganglionic intestinal innervation disorders include intestinal neuronal dysplasia (IND), hypoganglionosis and heterotopic ganglia. The pathogenesis of intestinal neuronal malformations is mainly attributed to development disorders of the ENS, in part caused by genetic defects. Furthermore, the ENS can sustain damage during the postnatal period by ischemic, inflammatory, autoimmunological processes or neurotoxic agents. The histopathological diagnosis of intestinal innervation disorders is achieved by enzyme- and immunohistochemical methods. The examination of the ENS can be carried out on mucosal, deep submucosal or full-thickness biopsies using serial transverse sections as well as on intestinal whole-mount preparations allowing a three-dimensional demonstration and assessment of the intramural plexus. Structural abnormalities of the myenteric and submucosal plexus and an abnormal content of neurotransmitters have been considered to be responsible for primary chronic constipation. However, until now no unified pathophysiological concept has been established due to the partly contradictory findings. Therefore, an important goal in patients with chronic constipation should be a detailed quantitative and qualitative assessment of the underlying neurohistopathology. The correlation of these data with functional parameters of intestinal motility may represent an useful tool for the differential diagnostic and therapeutic considerations.

Tyrosine phosphorylation of syndecan-1 and -4 cytoplasmic domains in adherent B82 fibroblasts.

The syndecans, a family of cell surface proteoglycans, have highly conserved cytoplasmic domains that bind proteins containing PDZ domains and co-localize with the actin cytoskeleton. The syndecan cytoplasmic domains contain four conserved tyrosine residues, two of which are located within favorable sequences for phosphorylation. Endogenous tyrosine phosphorylation of syndecans-1 and -4 is detected in adherent B82 fibroblasts. Approximately 1.5% of total syndecan is endogenously phosphorylated, while most, if not all, cell surface syndecan is phosphorylated following treatment with the tyrosine phosphatase inhibitor pervanadate. Syndecan phosphorylation is also detected in Raji-S1 and NMuMG cells, but only following treatment with vanadate or pervanadate, suggesting that endogenous phosphorylation is maintained in an "off" state in these cells. Endogenous syndecan phosphorylation in B82 cells is rapidly blocked by genistein (IC50 < 10 microM) confirming the presence of a constitutively active kinase and a corresponding tyrosine phosphatase. Phosphorylation is also inhibited by herbimycin A (IC50 < 1.0 microM) and staurosporine (IC50 < 1.0 nM), suggesting a role for Src family kinases in regulating syndecan phosphorylation. Together, these data suggest an important role for tyrosine phosphorylation of the syndecan cytoplasmic domains in regulating downstream signaling events in response to cell adhesion and/or growth factor activity.

Molecular interactions of the syndecan core proteins.

The syndecan family of cell-surface heparan sulfate proteoglycans participate in multiple cell behaviors ranging from growth factor signaling to cell adhesion. Participation in these activities is dependent on specific binding interactions of their heparan sulfate chains and molecular interactions of their core proteins with cytoskeletal and signaling molecules. The highly conserved features of the core proteins have long suggested important functions, which are only now beginning to be understood. Recent advances point to important roles for the extracellular, transmembrane and cytoplasmic domains of the syndecan core proteins in the assembly of these proteoglycans into an intracellular cytoskeletal and signaling apparatus. The proteins display interactions that may be common among the different family members, as well as interactions that provide signaling capabilities that are specific to individual members.

Touch-screen computerized education for patients with brain injuries.

The use of computer technology for patient education has increased in recent years. This article describes a study that measures the attitudes and perceptions of healthcare professionals and laypeople regarding the effectiveness of a multimedia computer, the Brain Injury Resource Center (BIRC), as an educational tool. The study focused on three major themes: (a) usefulness of the information presented, (b) effectiveness of the multimedia touch-screen computer methodology, and (c) the appropriate time for making this resource available. This prospective study, conducted in an acute care medical center, obtained healthcare professionals' evaluations using a written survey and responses from patients with brain injury and their families during interviews. The findings have yielded excellent ratings as to the ease of understanding and usefulness of the BIRC. By using sight, sound, and touch, such a multimedia learning center has the potential to simplify patient and family education.

Pervanadate activation of intracellular kinases leads to tyrosine phosphorylation and shedding of syndecan-1.

Syndecan-1 is a transmembrane haparan sulphate proteoglycan that binds extracellular matrices and growth factors, making it a candidate to act between these regulatory molecules and intracellular signalling pathways. It has a highly conserved transmembrane/cytoplasmic domain that contains four conserved tyrosines. One of these is in a consensus sequence for tyrosine kinase phosphorylation. As an initial step to investigating whether or not phosphorylation of these tyrosines is part of a signal-transduction pathway, we have monitored the tyrosine phosphorylation of syndecan-1 by cytoplasmic tyrosine kinases in intact cells. Tyrosine phosphorylation of syndecan-1 is observed when NMuMG cells are treated with sodium orthovanadate or pervanadate, which have been shown to activate intracellular tyrosine kinases. Initial studies with sodium orthovanadate demonstrate a slow accumulation of phosphotyrosine on syndecan-1 over the course of several hours. Pervanadate, a more effective inhibitor of phosphatases, allows detection of phosphotyrosine on syndecan-1 within 5 min, with peak phosphorylation seen by 15 min. Concurrently, in a second process activated by pervanadate, syndecan-1 ectodomain is cleaved and released into the culture medium. Two phosphorylated fragments of syndecan-1 of apparent sizes 6 and 8 kDa remain with the cell after shedding of the ectodomain. The 8 kDa size class appears to be a highly phosphorylated form of the 6 kDa product, as it disappears if samples are dephosphorylated. These fragments contain the C-terminus of syndecan-1 and also retain at least a portion of the transmembrane domain, suggesting that they are produced by a cell surface cleavage event. Thus pervanadate treatment of cells results in two effects of syndecan-1: (i) phosphorylation of one or more of its tyrosines via the action of a cytoplasmic kinase(s) and (ii) cleavage and release of the ectodomain into the medium, producing a C-terminal fragment containing the transmembrane/cytoplasmic domain.