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S Peters

Publications and source records attributed to S Peters.

At least 181 records · Page 10Linked to original sources
PubMed1995

Investigation of the active site of oligosaccharyltransferase from pig liver using synthetic tripeptides as tools.

Oligosaccharyltransferase (OST), an integral component of the endoplasmic-reticulum membrane, catalyses the transfer of dolichyl diphosphate-linked oligosaccharides to specific asparagine residues forming part of the Asn-Xaa-Thr/Ser sequence. We have studied the binding and catalytic properties of the enzyme from pig liver using peptide analogues derived from the acceptor peptide N-benzoyl-Asn-Gly-Thr-NHCH3 by replacing either asparagine or threonine with amino acids differing in size, stereochemistry, polarity and ionic properties. Acceptor studies showed that analogues of asparagine and threonine with bulkier side chains impaired recognition by OST. Reduction of the beta-amide carbonyl group of asparagine yielded a derivative that, although not glycosylated, was strongly inhibitory (50% inhibition at approximately 140 microM). This inhibition may be due to ion-pair formation involving the NH3+ group and a negatively charged base at the active site. Hydroxylation of asparagine at the beta-C position increased Km and decreased Vmax, indicating an effect on both binding and catalysis. The threo configuration at the beta-C atom of the hydroxyamino acid was essential for substrate binding. A peptide derivative obtained by replacement of the threonine beta-hydroxy group with an NH2 group was found to display acceptor activity. This shows that the primary amine is able to mimic the hydroxy group during transglycosylation. The pH optimum with this derivative is shifted by approximately 1 pH unit towards the basic region, indicating that the neutral NH2 group is the reactive species. The various data are discussed in terms of the catalytic mechanism of OST, particular emphasis being placed on the role of threonine/serine in increasing the nucleophilicity of the beta-amide of asparagine through hydrogen-binding.

Amino Acid Sequence↗
PubMed1995

Synthesis of the glycosyl amino acids N alpha-Fmoc-Ser[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-OPfp and N alpha-Fmoc-Thr[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-OPfp and the application in the solid-phase peptide synthesis of multiply glycosylated mucin peptides with Tn and T antigenic structures.

Two new glycosyl amino acids N alpha-Fmoc-Ser[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-+ ++OPfp and N alpha-Fmoc-Thr[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-+ ++OPfp were synthesized. Glycosylation of N alpha-Fmoc-Ser-OPfp or N alpha-Fmoc-Thr-OPfp with protected beta-D-Gal-(1-->3)-D-GalN3 donors afforded the glycosyl amino acids containing an activated C-terminus which could be utilized directly for solid-phase glycopeptide synthesis. The transformation of the 2-azido group into the acetamido derivative was achieved quantitatively at the end of the synthesis by treatment of the polymer-bound glycopeptide with thioacetic acid. The versatility of this strategy was demonstrated by the assembly of eight triply glycosylated mucin peptides which were synthesized simultaneously by multiple column techniques. The glycopeptides were prepared in order to investigate the substrate specificity of a galactosyltransferase.

Amino Acid Sequence↗
PubMed1995

Selective right ventricular angiography in apparently idiopathic ventricular fibrillation.

The definition of underlying heart disease in apparently idiopathic ventricular fibrillation seems to be important in regard to prognosis and choice of therapy. From October 1989, until August 1993, cardiac arrest due to the documented ventricular fibrillation occurred in eight consecutive patients with normal results on clinical examination, normal echocardiography, and normal or apparently nonspecific electrocardiogram (ECG) findings. Complete invasive investigations, including selective right ventricular angiography, were done; regional hypokinesia and segmental bulging of the right ventricle were found in seven patients (88%). Arrhythmogenic right ventricular dysplasia was suspected in these patients, although endomyocardial biopsy was not performed. After the finding of localized right precordial QRS prolongation of more than 110 ms in November 1993 in five patients, a retrospective, a more precise approach to QRS duration in standard ECG supported this diagnosis. Selective right ventricular angiography is of great help in identifying underlying heart disease in patients with apparently idiopathic ventricular fibrillation, and confirms ECG findings.

Adolescent↗
PubMed1995

Risk factors of cardiac arrest in arrhythmogenic right ventricular dysplasia.

Arrhythmogenic right ventricular dysplasia is an important cause of ventricular arrhythmia with a potential risk of sudden cardiac death in a young population. In order to define risk factors of cardiac arrest, angiographic and electrophysiological data from 60 patients with angiographically documented arrhythmogenic right ventricular dysplasia (of whom 20 also had spontaneous non-sustained ventricular arrhythmias, 27 sustained ventricular tachycardia and 13 suffered cardiac arrest with documented ventricular fibrillation before resuscitation) were analysed. There were no statistically significant differences in right ventricular volume, global right ventricular ejection fraction (RVEF), right ventricular structure, mean age at the time of diagnosis and angiographic left ventricular contraction abnormalities in the subgroups of patients with different forms of spontaneous arrhythmias. Only in a subgroup of patients with cardiac arrest and inducible sustained ventricular tachycardia did right ventricular volume (P < 0.05), ejection fraction (P < 0.001) and the amount of structural changes (P < 0.01) reveal significant results. A subgroup of patients with structural alterations and a low level of right ventricular function is at a high risk of cardiac arrest, although strenuous exercise and sport remain most important risk factors.

Adolescent↗
PubMed1995

Left ventricular impairment in arrhythmogenic right ventricular dysplasia: what we can learn from angiography.

Left ventricular impairment of arrhythmogenic right ventricular dysplasia is a common feature. Angiographic left ventricular contraction abnormalities can be found in more than 20% of patients with arrhythmogenic right ventricular dysplasia. Left ventricular impairment appears at all functional and morphological stages of the disease, even in cases with only slight or moderate right ventricular dysfunction. An event of aborted sudden cardiac death with documented ventricular fibrillation can be found in 56% of patients with left ventricular impairment. Left ventricular abnormalities seem to be an independent risk factor of sudden cardiac death; this is particularly true in patients with cardiac arrest as the first manifestation of the disease.

Adult↗
PubMed1995

Drug-induced mania.

Mania can occur by chance association during drug treatment, particularly in patients predisposed to mood disorder. Single case reports are unreliable, and evidence must be sought from large series of treated patients, particularly those with a matched control group. Drugs with a definite propensity to cause manic symptoms include levodopa, corticosteroids and anabolic-androgenic steroids. Antidepressants of the tricyclic and monoamine oxidase inhibitor classes can induce mania in patients with pre-existing bipolar affective disorder. Drugs which are probably capable of inducing mania, but for which the evidence is less scientifically secure, include other dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine and phencyclidine. Other drugs may induce mania rarely and idiosyncratically. Management involves discontinuation or dosage reduction of the suspected drug, if this is medically possible, and treatment of manic symptoms with antipsychotic drugs or lithium.

Adrenal Cortex Hormones↗
PubMed1995

Verrucous carcinoma with a dorsal sinus tract.

A verrucous carcinoma of the right foot was presented. A unique finding, a dorsal sinus tract at the base of the fourth toe, was found on examination, which communicated with the tumor. Other reports of a sinus tract extending to the dorsal surface of the foot could not be found in the literature.

Carcinoma, Verrucous↗
PubMed1995

Bone marrow transplantation for Philadelphia-chromosome-positive acute lymphoblastic leukemia.

The outcome of 14 bone marrow transplants (BMT) (autologous 4; allogeneic 10) for Philadelphia-chromosome (Ph1) positive acute lymphoblastic leukemia (ALL) was analyzed. Preparative regimens consisted of etoposide (VP16) (30 or 45 mg/kg BW) (n = 14), cyclophosphamide (CY)(120 mg/kg BW) (n = 14), and total body irradiation (TBI)(12 Gy) (n = 13) or busulfan (Bu)(16 mg/kg) (n = 1). All patients receiving autologous marrow were in complete remission (CR) (three patients in 1.CR, one patient in 2.CR) at the time of BMT. For allogeneic BMT (nine related, one unrelated donor), seven patients were in first CR, two patients in first refractory relapse, and one patient in second relapse. With a median follow-up of 503 days (range 93-1522 days), eight out of 14 patients are alive in remission (six out of 10 patients receiving allogeneic, and two out of four patients receiving autologous BMT). Disease-free survival for all patients is 46%. Causes of death were relapse (n = 3) and transplant-related toxicity (n = 3). All patients tested for the bcr/abl rearrangement by reverse transcriptase-polymerase chain reaction (RT-PCR) were negative 4 weeks post-BMT. Two of the three patients who subsequently relapsed were repeatedly RT-PCR positive prior to relapse (test not done in the third). Considering the negligible cure rate of Ph1-positive ALL with conventional chemotherapy regimens, our data support the concept of early (> or = 1 CR) BMT (allogeneic > autologous (purged) following triple therapy with TBI, VP16, and CY.

Adult↗
PubMed1994

UDPgalactose:glycoprotein-N-acetyl-D-galactosamine 3-beta-D-galactosyltransferase activity synthesizing O-glycan core 1 is controlled by the amino acid sequence and glycosylation of glycopeptide substrates.

In order to investigate the role of the peptide moiety of glycoproteins in the control of O-glycan biosynthesis, UDPgalactose:glycoprotein-N-acetyl-D-galactosamine 3-beta-D-galactosyltransferase (core 1 beta 3-Gal-T) from rat liver was tested for its specificity towards GalNAc-containing glycopeptide substrates. Series of glycopeptides have been synthesized by solid-phase synthesis, protected with an acetyl group on the amino terminal and an amide group on the carboxy terminal, based on variations of the repeat sequences of human intestinal mucin. Most glycopeptides were excellent substrates for core 1 beta 3-Gal-T compared to benzyl alpha-D-galactosamine as indicated by their relatively high Vmax/Km. The enzyme preferred threonine alpha-D-galactosamine Thr(GalNAc) to serine alpha-D-galactosamine. Pro on the carboxy-terminal side adjacent to Thr(GalNAc) was inhibitory. Negatively charged amino acids on either side showed a low Km; substrates with negatively charged amino acids on the amino-terminal side were highly efficient substrates, suggesting charge-charge interactions between enzyme and substrate. Gal beta 1-3GalNAc alpha residues adjacent to Thr(GalNAc) reduced the activity. Product analysis using glycopeptide substrates with three adjacent GalNAc residues showed incorporation of one, two and a small amount of three Gal residues per molecule with an uneven distribution of the potential di-galactosylated isomers. These studies indicate that, in addition to initial glycosylation, the second step in the glycosylation pathways of O-glycans is also controlled by the structure and glycosylation of the peptide core of substrates.

Amino Acid Sequence↗
PubMed1994

[Incidence and significance of morphologic and morphometric variants in selective right ventricular angiography in diagnosis of arrhythmogenic right ventricular disease].

BACKGROUND: In arrhythmogenic right ventricular disease it is difficult to find an imaging technique not only to suppose but to diagnose this disease. PATIENTS AND METHOD: In order to assess the value of selective right ventricular angiography in 104 patients with arrhythmogenic right ventricular disease (n = 53), WPW-syndrome (n = 2), sarcoidosis (n = 1), atrial septum defect (n = 8), dilative cardiomyopathy (n = 8), mitral valve disease (n = 17) and normal patterns (n = 15) right ventricular angiography was performed in biplane 30 degrees RAO/60 degrees LAO projection. Quantitative criteria such as RVEDVi, RVEF, regional wall motion in infundibular, inferior, apical and anterior segments and qualitative criteria such as deep horizontal fissures in trabecular hypertrophy, "pile d'assiettes" phenomenon and enddiastolic bulges with loss of trabecular structure were analysed. RESULTS: After extensice statistical analysis enddiastolic bulges with loss of trabecular structure and in less circumstance segmental contraction impairment of the right ventricle are the most valuable angiographic signs in order to diagnose ARVD. CONCLUSION: The best definition of arrhythmogenic right ventricular disease is obtained by extensive angiographic analysis with measurement of oxygen saturation and pressure curves in different positions, coronary angiography and biventricular angiography in order to distinguish between some in regard to right ventricular involvement similar cardiac entities.

Adult↗
PubMed1994

Human ductal adenocarcinomas of the pancreas express extracellular matrix proteins.

Pancreatic ductal adenocarcinomas are characterised by a dense connective tissue reaction. To test the hypothesis that stroma components are synthesised and produced by the tumour cells themselves, eight cell lines as well as six xenografted tumours from human ductal adenocarcinomas of the pancreas were examined for the expression of extracellular matrix proteins (ECM), using cDNA probes and antibodies to collagen types I, III and IV, vitronectin, fibronectin, undulin and laminin. All tumour cell lines (CAPAN-1, CAPAN-2, AsPC-1, BxPC-3, PANC-1, PaCa-2, PaCa-3, PaCa-44) and xenografted human pancreatic tumours expressed at least one of the examined ECM at the RNA (collagen type IV > laminin = fibronectin = vitronectin > collagen type III > undulin > collagen type I) or protein level (collagen type IV = collagen type III > vitronectin > laminin > collagen type I = fibronectin > undulin). In nude mouse tumours expression of laminin and collagen I was most pronounced in well-differentiated carcinomas. In a few tumours, collagen type III, vitronectin and undulin were expressed on the luminal side of the neoplastic glands, suggesting loss of normal polar differentiation. Incubation with fetal calf serum modulated ECM RNA levels to a varying extent in all but one cell line (AsPC-1). The results suggest that human pancreatic ductal adenocarcinomas cells are capable of synthesising and producing extracellular matrix proteins in vitro and in vivo, but that the extent and pattern of ECM expression differs between the various tumours and conditions tested.

Animals↗
PubMed1994

Interactions between the effects of propranolol and nicotine on radial maze performance of rats with lesions of the forebrain cholinergic projection system.

This experiment investigated the hypothesis that nicotine-induced regional release of noradrenaline contributes to the improvements in radial maze performance following nicotine treatment in rats with lesions to the forebrain cholinergic projection system (FCPS), by examining whether pretreatment with the noradrenergic beta-receptor antagonist propranolol abolished the facilitative effects of nicotine. After S-AMPA (8.0mM) lesions to the nuclei of origin of the FCPS in the nucleus basalis and medial septal areas, rats displayed long-lasting impairment in long-term reference and short-term working memory in both spatial (place) and associative (cue) radial maze tasks. Performance of control and lesioned rats was assessed after administration of nicotine (0.1mg/kg), propranolol (either 0.5 or 5.0mg/kg) and both treatments. Nicotine reduced working memory error rates in lesioned animals, but did not affect the performance of controls. Propranolol dose-relatedly increased error rates in both control and lesioned animals. Adverse effects were more marked in controls, all four types of error being increased under the high dose of propranolol, whereas in lesioned rats significant increases in error rates above baseline were confined to working memory. The low dose of propranolol, in conjunction with nicotine, abolished the improvement in working memory seen with nicotine alone in lesioned rats. However, under joint treatment with the high dose, the substantial increases in working memory error rates seen in lesioned rats after propranolol alone were reduced to baseline level. In controls, reduction in errors to baseline was seen only in the cue task; place task errors remained significantly elevated. These results suggest that both cholinergic depletion and noradrenergic blockade exert disruptive effects on cognition, but that these effects are largely independent, since an additive or interactive mechanism would be predicted to produce greater disruption, following noradrenergic blockade, in lesioned rather than in control animals. Although facilitative effects of nicotine were abolished with the low dose of propranolol, the results further suggest that these effects are independent of release of noradrenaline, since nicotine continued to reduce errors in control and lesioned animals following blockade of beta receptors with the high dose of propranolol.

Journal Article↗
PubMed1994

Susceptibility of glycans to beta-elimination in Fmoc-based O-glycopeptide synthesis.

In order to investigate the possible extent of beta-elimination occurring in Fmoc-based continuous-flow solid-phase glycopeptide synthesis, the influence of the pKb of the base used for N alpha-deprotection has been studied. A glycosylated pentapeptide was synthesized using 50% morpholine, 10% piperidine or 2% DBU, respectively, in DMF for deprotection. The dehydropentapeptide N alpha-Ac-Thr-Thr-delta Aba-Val-Thr-NH2, which would be formed in the case of beta-elimination, was prepared independently and used as a control in HPLC analysis; however, this product was not formed under any of the deprotection conditions applied. Furthermore, a 23 amino acid long glycopeptide from human intestinal mucin was prepared using 2% DBU as a base for Fmoc cleavage, and similarly no beta-elimination was observed. The glycopeptide products were subjected to a prolonged treatment with sodium hydroxide in methanol/water without significant formation of byproducts, and the pure glycopeptides were isolated and characterized by 1H-NMR spectroscopy.

Amino Acid Sequence↗
PubMed1994

Engraftment of normal murine marrow into nonmyeloablated host mice.

When 200 x 10(6) male BALB/c cells are given by tail vein injection to female nonmyeloablated hosts in one injection, a relatively low engraftment percentage is seen, but when the same total number of cells is given over five injections (separated by 24 hours), the observed engraftment is much higher. A further increase in engraftment appears to occur when the same number of cells is given in 10 injections separated by at least 24 hours. These data suggest that somewhere between 5 and 10% of marrow niches are available at intervals of 24 or more hours and that the keys to high levels of engraftment are the cell cycle status of the engrafting stem cell and the schedule of engraftment.

Animals↗
PubMed1994

In vitro and in vivo studies of stromal niches.

Lymphohematopoiesis occurs in the densely packed environment of the intramedullary spaces. Primitive lymphohematopoietic stem cells exist in close apposition to a variety of supportive cells including both hemopoietic and nonhemopoietic lineages. Using an in vitro long-term Dexter liquid culture system, we have established that a variety of cytokines are produced constitutively by such stromal cells in culture. These cytokines include Steel factor, interleukin-6 (IL-6), and colony-stimulating factor (CSF-1). Granulocyte-CSF and granulocyte-macrophage-CSF mRNA can be detected after refeeding of cultures, although in quiescent cultures message for these factors is difficult to detect. Interleukin-3, IL-4, and IL-5 are not detectable by standard Northern blot analysis or bioassay of condition media. However, IL-3--detectable by reverse-transcriptase PCR and biologic activity--was confirmed by growth of factor-dependent cells on stromal cells with IL-3 antibody blocking of such growth. Stem cells resident on such stromal cells are mirrored by the high proliferative potential colony-forming cell assay and are responsive to a relatively large number of cytokines, with Steel factor being of central importance, appearing to be a critical component of various synergistic combinations. Steel factor allows reduced levels of other factors in such combinations and works early in a temporal sequence. Hematopoietic stem cells can engraft in normal nonmyeloablated hosts. Using a male/female BALB/c transplantation model, we have shown high rates of engraftment into normal animals, out after marrow infusion to 25 months, after marrow infusion and that post-5-fluorouracil bone marrow is quite deficient in such engraftment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Measles vaccine failures: lack of sustained measles-specific immunoglobulin G responses in revaccinated adolescents and young adults.

The measles-specific antibody responses of seronegative adolescents and young adults were evaluated after revaccination. Of 1650 previously vaccinated healthy volunteers between the ages of 10 and 30 years, 4.4% were found to be seronegative for measles antibodies and 9.9% had equivocal titers. Seronegative volunteers were revaccinated to measles and followed serially for development of measles-specific IgG. Of 43 subjects followed for at least 1 year, only 58% developed and maintained positive antibody titers; 12% never developed positive titers and 30% initially developed titers that fell below positive levels within 1 year. The peak titers achieved by those subjects who responded transiently were lower than those achieved by subjects who developed sustained responses. Thus even after the recommended two dose schedule of the current measles vaccine, some adolescents and young adults lack protective titers of measles-specific antibody.

Adolescent↗
PubMed1993

Intravenous pentoxifylline failed to prevent transplant-related toxicities in allogeneic bone marrow transplant recipients.

Based on encouraging results of a recently published study on the clinical usefulness of oral pentoxifylline (PTX) to reduce transplant-related toxicities, prophylactic pentoxifylline was administered to 31 consecutive allogeneic BMT recipients with hematological malignancies. Patients received PTX as a continuous infusion at increasing dose levels (0.50, 0.75, 1.00 and 1.25 mg/kg/h) starting 1 day prior to the conditioning regimen. At all dose levels, PTX was well tolerated with no significant side-effects. When compared with a historical control group of 61 consecutively transplanted allogeneic BMT recipients, PTX patients did not appear to experience less gastrointestinal (moderate and severe mucositis: 100% vs 68%, p < 0.001), hepatic (hyperbilirubinemia > 1.5 mg/dl: 84% vs 30%, p < 0.001) or renal (creatinine > 1.5 mg/dl: 16% vs 27%, NS) toxicity or to have a lower incidence of GVHD > or = grade III (21% vs 22%, NS). Using i.v. PTX, we were unable to reproduce the reduction in morbidity and mortality in patients undergoing BMT which has been described for prophylactic oral PTX.

Adolescent↗