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Biomedical subjects

M John

Publications and source records attributed to M John.

At least 91 records · Page 5Linked to original sources
PubMed1998

Guanylin stimulates regulated secretion from human neuroendocrine pancreatic cells.

BACKGROUND & AIMS: Gastroenteropancreatic neuroendocrine cells secrete chemical messengers in a calcium-dependent fashion. So far, other second messenger systems involved in regulated secretion have gained little attention. The aim of this study was to characterize guanosine 3',5'-cyclic monophosphate (cGMP)-mediated vesicular secretion in pancreatic neuroendocrine cells. METHODS: In a human pancreatic cell line, BON, cyclic nucleotide levels and chromogranin A release were monitored with specific immunoassays. Uptake and release of gamma-aminobutyric acid were measured. Intracellular Ca2+ concentration was monitored with fura-2. Guanylyl cyclase C was analyzed by reverse-transcription polymerase chain reaction. RESULTS: Guanylin increased cGMP concentrations in BON cells via guanylyl cyclase C. Stimulation of the cGMP pathway by guanylin or Escherichia coli heat-stable enterotoxin increased the release of chromogranin A and gamma-aminobutyric acid from BON cells. This effect was mimicked by the cGMP analogue 8-bromo-cGMP. CONCLUSIONS: Guanylin and STa stimulate the regulated secretion from BON cells via guanylyl cyclase C and cGMP. Our study yields novel information about secretory properties of guanylin, mediated via a signal transduction pathway, increasing cGMP and leading to regulated secretion of neuroendocrine cells.

Bacterial Toxins↗
PubMed1998

Immortalized gonadotropin-releasing hormone neurons secrete gamma-aminobutyric acid-evidence for an autocrine regulation.

The immortalized hypothalamic neuronal cell lines GT1-1 and GT1-7 represent unique model systems to investigate the physiological control of gonadotropin-releasing hormone (GnRH) secretion. Using immunofluorescence microscopy, key proteins of regulated exocytosis, e.g. synaptotagmin, synaptobrevin and SNAP-25 (synaptosomal associated protein of 25 kDa) were found in GT1 neurons. In addition, GT1 neurons contained synaptophysin, a marker protein for small synaptic vesicles (SSVs) which are responsible for the storage of neurotransmitters such as gamma-aminobutyric acid (GABA). Upon subcellular fractionation, a lighter vesicle population characterized by synaptophysin separated from a denser vesicle population containing GnRH. Both vesicle populations contained synaptobrevin and synaptotagmin. Besides GnRH, GT1 neurons expressed glutamic acid decarboxylase at the mRNA-level and synthesized GABA. More importantly, GT1 neurons took up and stored 3H-GABA. The stored GABA was released after stimulation with increasing K+ concentrations and by alpha-latrotoxin. Reducing the extracellular Ca2+-concentration abolished stimulated secretion, indicating that GABA was released by regulated exocytosis. Hormone secretion from GT1 neurons is controlled by GABA via GABA(A) and GABA(B) receptors reflecting the situation in vivo. Our data provide the first evidence that GT1 neurons possess a second regulated secretory pathway sustained by SSVs storing and releasing GABA. The released GABA influences GnRH secretion by an auto- or paracrine loop.

Animals↗
PubMed1998

Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1alpha, granulocyte-macrophage colony-stimulating factor, and interferon-gamma release from alveolar macrophages in asthma.

We determined the effect of inhaled corticosteroid, budesonide, on the release of the anti-inflammatory cytokine, interleukin-10 (IL-10), and of pro-inflammatory cytokines, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF), from blood monocytes and alveolar macrophages of mild asthmatic subjects in a double-blind, cross-over, placebo-controlled study. Budesonide reduced bronchial hyperresponsiveness and improved baseline FEV1. Alveolar macrophages were obtained by bronchoalveolar lavage performed at the end of each treatment phase. IL-10 from blood monocytes was not altered, but both IL-10 mRNA and protein expression from alveolar macrophages stimulated by lipopolysaccharide and IL-1beta were increased after corticosteroid therapy. By contrast, alveolar macrophages released significantly less MIP-1alpha, IFN-gamma, and GM-CSF after steroid treatment. In comparison to alveolar macrophages from normal nonasthmatic volunteers, those from asthmatic patients released more MIP-1alpha, IFN-gamma, and GM-CSF but lower amounts of IL-10 particularly at baseline and after IL-1beta stimulation. The ability of steroids to inhibit pro-inflammatory cytokines but to enhance the anti-inflammatory cytokine such as IL-10 may contribute to their beneficial actions in asthma. Asthma is characterized by alveolar macrophages exhibiting both an enhanced capacity to release pro-inflammatory cytokines and a reduced capacity to produce IL-10.

Administration, Inhalation↗
PubMed1998

Expression and release of interleukin-8 by human airway smooth muscle cells: inhibition by Th-2 cytokines and corticosteroids.

Interleukin (IL)-8 is a C-X-C chemokine that potently chemoattracts and activates neutrophils. We determined whether IL-8 could be produced by human airway smooth muscle cells in culture and examined its regulation. TNF-alpha stimulated IL-8 mRNA expression and protein release in a time- and dose-dependent manner, whereas IFN-gamma alone had no effect. Both cytokines together did not induce greater IL-8 release compared to TNF-alpha alone. IL-1beta was more potent in inducing IL-8 release and, together with TNF-alpha, there was a synergistic augmentation of IL-8 release. IL-8 release induced by TNF-alpha and IFN-gamma was partly inhibited by the Th-2-derived cytokines IL-4, IL-10, and IL-13, as well as by dexamethasone. In addition to its contractile responses, airway smooth muscle cells have synthetic and secretory potential with the release of IL-8 and subsequent recruitment and activation of neutrophils in the airways. Release of IL-8 can be modulated by Th-2-derived cytokines and corticosteroids.

Adrenal Cortex Hormones↗
PubMed1998

Radiation therapy for rectosigmoid and rectal cancer: results of the 1992-1994 Patterns of Care process survey.

PURPOSE: To determine the US national practice standards for patients with adenocarcinoma of the rectum treated in radiation oncology facilities. MATERIALS AND METHODS: A national survey of 57 institutions identified 507 eligible patients who received radiation therapy as a component of their treatment for rectal cancer. A stratified two-stage cluster sampling with simple random sampling at each stage for each stratum was used and on-site surveys were performed. RESULTS: Of the 507 patients, 378 (75%) received postoperative therapy, 110 (22%) received preoperative therapy, 17 (2%) received both preoperative and postoperative therapy, and less than 0.5% received intraoperative radiation alone. To more accurately assess the utilization of modern radiation techniques as well as recommendations of the National Cancer Institute (NCI)-sponsored, randomized, postoperative, adjuvant combined modality therapy rectal cancer trials into current practice, the analysis was limited to the 243 (48%) patients with tumor, node, and metastasis staging system classification T3 and/or N1-2M0 disease who underwent conventional surgery with negative margins. Although only 7% were treated on a clinical trial, 90% received chemotherapy for a median of 21 weeks. Most were treated with modern radiation treatment techniques. In contrast, techniques to identify and help exclude the small bowel from the radiation field were not routinely used. CONCLUSION: Despite the fact that only 7% of patients with T3 and/or N1-2M0 disease were treated on a clinical trial, such trials appear to have resulted in a positive influence on the standard of practice within the oncology community. Although there are still some deficiencies, the majority of these patients received combined modality therapy and were treated with modern radiation therapy techniques.

Adenocarcinoma↗
PubMed1998

Factor V Leiden (G1691A), the prothrombin 3'-untranslated region variant (G20210A) and thermolabile methylenetetrahydrofolate reductase (C677T): a single genetic test genotypes all three loci--determination of frequencies in the S. Wales population of the UK.

Simultaneous genetic diagnosis of factor V (FV) Leiden (G1691A), the prothrombin variant (G20210A) and the thermolabile methylenetetrahydrofolate reductase (MTHFR) variant (C677T) has been achieved using multiplex heteroduplex analysis. All three loci are amplified in a single polymerase chain reaction (PCR) containing test DNA and three heteroduplex generators, respectively detecting the three nucleotide substitutions. After PCR, the products are analysed directly without further manipulation and the resulting heteroduplex profiles permit straightforward interpretation of the respective genotypes. The multiplex test has been used to assess the prevalence and allele frequency of each of the three nucleotide substitutions in 300 individuals (150 males and 150 females) from the local (S. Wales) population. A prevalence of 8% and an allele frequency of 0.040 +/- 0.015 (95% confidence interval) was obtained for FV Leiden; the prothrombin variant showed a prevalence of 1% and an allele frequency of 0.007 +/- 0.006 (95% confidence interval); the MTHFR mutation showed a prevalence of 60% and an allele frequency of 0.377 +/- 0.039 (95% confidence interval). This method is applicable to investigation of large cohorts of patients with arterial or venous thrombotic disease.

Cohort Studies↗
PubMed1997

Lipochitooligosaccharide-induced tobacco cells release a peptide as mediator of the glycolipid signal.

Lipochitooligosaccharides (LCOs) are plant growth regulators that promote at subfemtomolar concentrations cell division in tobacco protoplasts. In response to LCO treatment, tobacco cells release a second growth factor that fully mediates the growth-promoting activities of the initial extracellular LCO stimulus. This diffusible growth factor was isolated from the protoplasts' culture filtrate and shown to be a peptide. We report that the LCO-induced mitogen released by tobacco cells and a synthetic heptadecapeptide derived from region 2 of the tobacco homolog of the early nodulin gene ENOD40 are antigenically related and qualitatively indistinguishable in their ability to stimulate cell division.

Amino Acid Sequence↗
PubMed1997

DNA binding and transactivation properties of Fos variants with homodimerization capacity.

The mammalian Fos and Fos-related proteins are unable to form homodimers and to bind DNA in the absence of a second protein, like c-Jun for example. In order to study the implications of hydrophobic point mutations in the c-Fox leucine zipper on DNA binding of the entire c-Fos protein, we have constructed and purified a set of Fos mutant proteins harboring one or several isoleucine or leucine residues in the five Fos zipper a positions. We show that a single point mutation in the hydrophobic interface of the c-Fos leucine zipper enables the c-Fos mutant protein to bind specifically to an oligonucleotide duplex harboring the TRE consensus sequence TGA(C/G)TCA. This point mutation (Thr196-->Ile) is situated in the a position of the second heptade (a2) of the Fos zipper. The introduction of additional isoleucine residues in the other a positions progressively increases the DNA binding affinity of these homodimerizing Fos zipper variants. Heterodimerization of these c-Fos variants with c-Jun reveals a complex behavior, in that the DNA binding affinity of these heterodimers does not simply increase with the number of isoleucine side chains in position a. For example, a c-Fos variant harboring a wild-type Thr in position a1 aad Ile in the four other a positions (c-Fos4I) interacts more tightly with c-Jun than a variant harboring Ile in all five a positions (c-Fos5I). The same holds true for the corresponding leucine variants, suggesting that the wild-type a1 residue of the Fox zipper (Thr162) is thermodynamically relevant for Fos-Jun heterodimer formations and DNA binding. The c-Fos4I variant forms heterodimers with c-Jun slightly better than the wild-type zipper protein, suggesting that the driving force for Fos-Jun heterodimerization is not the simple fact that the Fos protein is unable to form homodimers. These c-Fos variants were further tested for their transactivation properties in F9 and NIH3T3 cells. At low expression levels the most efficiently homodimerizing variant (c-Fos5I) activates transcription in F9 cells about 6-fold. However part of this activation may be due to the formation of heterodimers with a member of the Jun family (like JunD for example), since a wild type c-Fos expression vector confers a 3-fold activation under these conditions. In the case of the homodimerizing c-Fos variants however, this activation is abrogated at higher expression levels due to a strong inhibition of basal transcription activity.

3T3 Cells↗
PubMed1997

PDGF-BB increases endothelial migration on cord movements during angiogenesis in vitro.

To explore direct effects of platelet-derived growth factor (PDGF) on endothelial cells during angiogenesis in vitro, we have used cloned bovine aortic endothelial cells that spontaneously form cord structures. Recently we have shown that cells forming these endothelial cords express PDGF beta-receptors and that PDGF-BB can contribute to cellular proliferation and cord formation. In this study we investigated whether PDGF-induced cellular migration might also contribute to endothelial repair and angiogenesis in vitro. Ten individual endothelial cells in cords were tracked at an early stage of cord formation by video-timelapse microscopy. PDGF-BB (100 ng/ml) induced an increase in endothelial cell movement of 67 +/- 15% as compared with diluent control. Interestingly, PDGF-BB also increased movements of entire cord structures, followed at branching points, by 53 +/- 12% over diluent control. Taken together, these video-timelapse experiments suggested that the apparent movements of single endothelial cord cells might also be due to the motion of entire underlying cord structures in response to PDGF. To analyze the response of single endothelial cord cells we therefore examined whether PDGF-induced migration contributes to endothelial repair. Abrasions were applied with a razor blade to confluent monolayers of endothelial cells at an intermediate stage of cord formation. PDGF-BB concentration-dependently increased the distance to which cord-forming endothelial cells migrated into the abrasion. An increased number of elongated, i.e., probably migrating, endothelial cells was found in the abrasion in response to PDGF-BB. However, there was no effect of PDGF-BB on the total number of endothelial cells found in the abrasion. PDGF-AA affected neither the distance to which the cells migrated nor the number of elongated cells. Actin and tubulin stainings revealed that these cytoskeletal structures were not appreciably altered by PDGF-BB. Furthermore, urokinase-type plasminogen activator transcripts were not modulated in response to PDGF-BB. We conclude that in this model of angiogenesis in vitro PDGF-BB can elicit the movement of entire cord structures, possibly via u-PA-independent mechanisms. PDGF-BB also controls the migration of single cord-forming endothelial cells. Thus, PDGF-BB possibly contributes to endothelial repair and angiogenesis by direct effects on proliferation and composite movements of PDGF beta-receptor-expressing endothelial cells and cords.

Adult↗
PubMed1997

Human airway smooth muscle cells express and release RANTES in response to T helper 1 cytokines: regulation by T helper 2 cytokines and corticosteroids.

RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong chemotactic activity for eosinophils, lymphocytes, and monocytes. We determined the regulation of RANTES production by human airway smooth muscle cells in culture. While TNF-alpha, but not IFN-gamma, increased RANTES mRNA expression and protein release, the combination of TNF-alpha and IFN-gamma caused a greater degree of expression and release in a time- and dose-dependent manner. Sequential treatment of airway smooth muscle cells with TNF-alpha and IFN-gamma showed that IFN-gamma sensitized the cells to the stimulatory effect of TNF-alpha. Using a modified Boyden chamber technique, RANTES separated by reverse-phase liquid chromatography from cell culture supernatants of airway smooth muscle cells stimulated by TNF-alpha and IFN-gamma showed a strong chemoattractant effect on human eosinophils, an effect inhibited by an anti-RANTES Ab. RANTES production induced by TNF-alpha and IFN-gamma was inhibited partly by the Th2-derived cytokines, IL-4, IL-10, and IL-13, as well as by dexamethasone. Our studies indicate that, in addition to contractile responses and mitogenesis, airway smooth muscle cells have synthetic and secretory potential with the release of RANTES. They may participate in chronic airway inflammation by interacting with both Th1- and Th2-derived cytokines to modulate chemoattractant activity for eosinophils, activated T lymphocytes, and monocytes/macrophages.

Adrenal Cortex Hormones↗
PubMed1997

Expression of epidermal growth factor receptor in gestational trophoblastic diseases.

Gestational trophoblastic disease is an abnormal condition of the placenta, the incidence of which is very high in the State of Kerala, India. The biology of this disease is vague and methods to determine the malignant potential are limited. Placentae of normal (50) and molar pregnancies (95), including 32 showing persistent disease, were used for the study. Epidermal growth factor (EGFR), expression was evaluated by immunohistochemistry using monoclonal antibody, and quantified using the 125I-EGF-binding assay. EGFR was expressed more strongly in molar placentae than in normal placentae of similar gestational age, and was strong in the molar placentae of all gestational ages, whereas expression was mainly restricted to the first and second trimesters in normal placentae. Moles with early presenting symptoms (before 16 weeks) were at a higher risk of developing persistent disease. To conclude, the immunohistochemical study shows high expression of EGFR in early normal placentae and in moles, linking its role to the proliferative and differentiating activity of trophoblasts. Tumours with a histological diagnosis of invasive moles and choriocarcinoma showed very strong binding of EGFR. The present observations also suggest the possibility of mutated EGF receptors being present in persistent trophoblastic disease.

Adult↗
PubMed1997

Microspectroscopic imaging of nodulation factor-binding sites on living Vicia sativa roots using a novel bioactive fluorescent nodulation factor.

A novel bioactive fluorescent nodulation (Nod) factor, NodRlv-IV(BODIPY FL-C16), has been synthesized by attaching a BODIPY FL-C16 acyl chain to the primary amino group of chitotetraose deacetylated at the nonreducing terminus by recombinant NodB. The binding of the fluorescent Nod factor to root systems of Vicia sativa was investigated with fluorescence spectral imaging microscopy (FSPIM) and fluorescence ratio imaging microscopy (FRIM). Spatially resolved fluorescence spectra of living and labeled Vicia sativa root systems were measured by FSPIM. Strong autofluorescence, inherent to many plant systems when excited at 488 nm, was corrected for by utilizing the difference in fluorescence emission spectra of the autofluorescence and NodRlv-IV(BODIPY FL-C16). A methodology is presented to break down the in situ fluorescence emission spectra into spatially resolved autofluorescence and BODIPY FL fluorescence spectra. Furthermore, an FRIM method was developed for correcting autofluorescence in fluorescence micrographs for this system. After autofluorescence correction it was shown that NodRlv-IV(BODIPY FL-C16) was concentrated in the root hairs, but was also bound to other parts of the root surface.

Binding Sites↗
PubMed1997

Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity.

When transcriptionally active, the human immunodeficiency virus (HIV) promoter contains a nucleosome-free region encompassing both the promoter/enhancer region and a large region (255 nucleotides [nt]) downstream of the transcription start site. We have previously identified new binding sites for transcription factors downstream of the transcription start site (nt 465 to 720): three AP-1 sites (I, II, and III), an AP3-like motif (AP3-L), a downstream binding factor (DBF) site, and juxtaposed Sp1 sites. Here, we show that the DBF site is an interferon-responsive factor (IRF) binding site and that the AP3-L motif binds the T-cell-specific factor NF-AT. Mutations that abolish the binding of each factor to its cognate site are introduced in an infectious HIV-1 molecular clone to study their effect on HIV-1 transcription and replication. Individual mutation of the DBF or AP3-L site as well as the double mutation AP-1(III)/AP3-L did not affect HIV-1 replication compared to that of the wild-type virus. In contrast, proviruses carrying mutations in the Sp1 sites were totally defective in terms of replication. Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the AP-1(III), AP3-L, and DBF sites and in the AP3-L and DBF-sites, whereas viruses mutated in the AP-1(I,II,III) and AP3-L sites and in the AP-1(I,II,III), AP3-L, and DBF sites exhibited a severely defective replicative phenotype. No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their HIV genomic RNA. Measurement of the transcriptional activity of the HIV-1 promoter after transient transfection of the HIV-1 provirus DNA or of long terminal repeat-luciferase constructs showed a positive correlation between the transcriptional and the replication defects for most mutants.

Base Sequence↗
PubMed1997

Cytokines derived from alveolar macrophages induce fever after bronchoscopy and bronchoalveolar lavage.

As much as one-third of patients develop fever and flu-like symptoms after fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) for yet unknown reasons. The aim of the present study was to investigate factors mediating these side effects. Fifty consecutive patients with various pulmonary diseases who underwent FOB without further interventions (n = 30) or combined with BAL (n = 20) were enrolled. Serum levels of the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha were determined directly prior to (t0), directly after (t1), and 6 h after (t2) the procedures by ELISA. In parallel, blood cultures were drawn at t2. At to and t1, generally only low cytokine concentrations could be detected. At t2, however, significant increases of cytokine levels were found. IL-6 and TNF-alpha were significantly higher in patients after BAL than in patients after FOB. Comparing patients who developed fever (n = 12) with those who did not (n = 38), irrespective of the endoscopic procedures performed, dramatic increases of all three cytokines were detected in febrile patients that were significantly higher than in patients without fever. In the FOB group only patients who received local anesthesia by prilocaine bolus injection into the airways via the working channel of the bronchoscope developed fever and increases of IL-6 and IL-beta, whereas patients anaesthetized by inhalation of a prilocaine aerosol remained afebrile and had slight IL-6 increases only. There was a highly significant correlation between IL-6 values at t2 and the number of BAL alveolar macrophages (r = 0.98). All blood cultures remained sterile. These results indicate that fever after FOB and BAL is induced by proinflammatory cytokines derived from alveolar macrophages activated by instillation of fluid into the airways.

Adult↗
PubMed1997

Evaluation of luteal phase in normal and infertile women.

Evaluation of luteal phase function is an important part of fertility evaluation in the female. Among fifty clinically identified patients with primary infertility certain well-established laboratory methods were used to identify the luteal phase defect. These methods included serum progesterone assays, endometrial biopsy, vaginal cytology, basal body temperatures and cervical mucus scoring, with appropriate controls. Based on both endometrial biopsy which was two or more days out of phase and the serum progesterone level of less than 2.5 ng/ml, luteal phase defect was found in five patients among the 50 patients (10 percent). It was found that an endometrial biopsy which was well dated showed a definite correlation with the progesterone assays and could be considered as the most easily performed and reliable indicator, useful in detecting a luteal phase defect.

Adult↗
PubMed1997

Expression of epidermal growth factor in gestational trophoblastic disease (GTD).

Gestational Trophoblastic Disease (GTD) is an abnormal condition of the placenta, the incidence of which is very high in the State of Kerala, India. The biology of the disease is vague and methods to determine the malignant potentialis limited. Placentae of normal (50) and molar pregnancy (95) including 32 patients showing persistent disease were used in this study. EGF expression was analyzed by immunohistochemistry using monoclonal antibody to EGF and quantitated using isotope labelled antibody to EGF. EGF was expressed more strongly in molar placentae in all gestational ages in comparison with normal placentae of similar gestational age, the expression being restricted mainly to first and second trimesters in normal placentae. Moles with early presenting symptoms (< 12 weeks) were at a higher risk for developing persistent disease. In conclusion, the immunohistochemical study shows high expression of EGF in early normal placentae and moles linking its role to proliferative and differentiating activity of trophoblasts. Tumors with histological diagnosis of invasive moles and choriocarcinoma showed very strong binding of EGF and thus EGF has the potential of identifying high risk lesions.

Adolescent↗
PubMed1997

[Molecules of regulated secretion are differentiation markers of neuroendocrine tumors].

Regulated secretory vesicles of neuroendocrine cells encompass two distinct types, i.e. hormone-storing large dense core vesicles (LDCV) and neuron-like small synaptic vesicles (SSVs). The membranes of the vesicles and the acceptor organelles contain proteins which are essential for targeted membrane fusion and protein transport (SNARE hypothesis). Membrane proteins of SSV analogues such as synaptophysin, synaptobrevin (v-SNARE) and synaptotagmin are key proteins of neurosecretion. The plasma membrane proteins syntaxin and SNAP25 (t-SNARE) are indispensible for this locking/fusion process. This study was done to identify the molecular components of LDCVs, SSV analogues and the SNARE-complex in neuroendocrine tumors. Immunohistochemical analysis using a panel of antibodies was done on file material from benign or low-grade malignant neuroendocrine tumors (n = 20) and high-grade malignant intermediate or small cell carcinomas (n = 27) of the gut, pancreas and lung. The statistical evaluation of our results indicate that the expression of all marker molecules of the regulated secretory pathway is significantly reduced in high-grade malignant carcinomas when compared to benign or low-grade malignant tumors. The reduction of the LDCV matrix protein chromogranin A and of the SSV membrane protein synaptobrevin is highly significant in high-grade malignant carcinomas, which may even loose these proteins. In contrast, the synthesis of synaptophysin and the t-SNARE-protein SNAP25 appears to be better maintained even in small cell carcinomas. We conclude that the immunohistochemical diagnosis of high-grade malignant neuroendocrine tumors should mainly be based on the identification of SSV- and SNARE-proteins, especially synaptophysin and SNAP25. These marker molecules of the regulated secretory pathway are valuable tools for the diagnosis and classification of neuroendocrine tumors and contribute to the understanding of cellular differentiation pathways.

Biomarkers↗