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J Petersen

Publications and source records attributed to J Petersen.

At least 55 records · Page 3Linked to original sources
PubMed2000

Oxo-vanadium as a spin probe for the investigation of the metal coordination environment of imidazole glycerol phosphate dehydratase.

Imidazole glycerol phosphate dehydratase (IGPD) catalyses the dehydration of imidazole glycerol phosphate to imidazole acetol phosphate, an important late step in the biosynthesis of histidine. IGPD, isolated as a low molecular weight and inactive apo-form, assembles with specific divalent metal cations to form a catalytically active high molecular weight metalloenzyme. Oxo-vanadium ions also assemble the protein into, apparently, the same high molecular weight form but, uniquely, yield a protein without catalytic activity. The VO2+ derivative of IGPD has been investigated by electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR) and electron spin echo envelope modulation (ESEEM) spectroscopy. The spin Hamiltonian parameters indicate the presence of multiple 14N nuclei in the inner coordination sphere of VO2+ which is corroborated by ENDOR and ESEEM spectra showing resonances attributable to interactions with 14N nuclei. The isotropic superhyperfine coupling component of about 7 MHz determined by ENDOR is consistent with a nitrogen of coordinated histidine imidazole(s). The ESEEM Fourier-transform spectra further support the notion that the VO2+ substituted enzyme contains inner-sphere nitrogen ligands. The isotropic and anisotropic 14N superhyperfine coupling components are similar to those reported for other equatorially coordinated enzymatic histidine imidazole systems. ESEEM resonances from axial 14N ligands are discussed.

Electron Spin Resonance Spectroscopy↗
PubMed2000

A novel particulate form of Ca(2+)/calmodulin-dependent [correction of Ca(2+)/CaMKII-dependent] protein kinase II in neurons.

Cytoskeletal and postsynaptic density (PSD) fractions from forebrain contain discrete spherical structures that are immunopositive for Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Spherical structures viewed by rotary shadow electron microscopy have an average diameter of approximately 100 nm and, in distinction to postsynaptic densities, do not immunolabel for PSD-95. These structures were purified to near homogeneity by extraction with the detergent N-lauryl sarcosinate. Biochemical analysis revealed that CaMKII accounts for virtually all of the protein in the purified preparation, suggesting that spherical structures are clusters of self-associated CaMKII. Exposure of cultured hippocampal neurons to a mitochondrial uncoupler in glucose-free medium promotes the formation of numerous CaMKII-immunopositive structures identical in size and shape to the CaMKII clusters observed in subcellular fractions. Clustering of CaMKII would reduce its kinase function by preventing its access to fixed substrates. On the other hand, clustering would not affect the ability of the large cellular pool of CaMKII to act as a calmodulin sink, as demonstrated by the Ca(2+)-dependent binding of gold-conjugated calmodulin to CaMKII clusters. We propose that the observed clustering of CaMKII into spherical structures is a protective mechanism preventing excessive protein phosphorylation upon loss of Ca(2+) homeostasis, without compromising calmodulin regulation.

Animals↗
PubMed2000

A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary-artery stents.

BACKGROUND: The introduction of an effective antiplatelet therapy with aspirin and ticlopidine after the placement of coronary-artery stents has decreased the risk of thrombotic stent occlusions (TSO) and hemorrhagic complications. However, the use of ticlopidine is limited by hematological and gastrointestinal adverse effects. The safety and efficacy of clopidogrel after stenting remains to be established. METHODS AND RESULTS: After successful coronary stenting during elective or emergency percutaneous transluminal coronary angioplasty, 700 patients with 899 lesions were randomly assigned to receive a 4-week course of either 500 mg ticlopidine (n=345) or 75 mg clopidogrel (n=355), in addition to 100 mg aspirin. All the following clinical events reflecting TSO were included in the prespecified primary cardiac endpoint: cardiac death, urgent target vessel revascularization, angiographically documented TSO, or nonfatal myocardial infarction within 30 days. The primary noncardiac endpoint was defined as noncardiac death, stroke, severe peripheral vascular or hemorrhagic events, or any adverse event resulting in discontinuation of study medication. Cardiac events occurred in 17 patients [11 (3.1%) with clopidogrel and 6 (1.7%) with ticlopidine (P=0.24)]. The primary noncardiac endpoint was observed in 16 patients (4.5%) assigned to receive clopidogrel versus 33 patients (9.6%) assigned to receive ticlopidine (P=0.01). CONCLUSIONS: After the placement of coronary-artery stents in unselected patients, antiplatelet therapy with aspirin and clopidogrel seems to be comparably safe and effective as aspirin and ticlopidine. Noncardiac events were significantly reduced with clopidogrel.

Aged↗
PubMed2000

Production of interleukin (IL)-1beta, IL-1 receptor antagonist and IL-10 by blood mononuclear cells in chronic arthritis.

Joint erosion is a prevalent feature of rheumatoid arthritis (RA) but not of many other chronic inflammatory arthritides (non-RA). Joint destruction is mediated by cytokines, primarily interleukin (IL)-1 and tumour necrosis factor. Less erosive activity in patients with non-RA compared to RA might be related to factors that inhibit production and/or function of IL-1. Release of IL-1beta, and the two antagonists, IL-1 receptor antagonist (IL-1ra) and IL-10 from blood mononuclear cells were therefore quantitated by ELISA in 22 patients with RA, 11 with non-RA and 15 healthy age-matched controls. Release of IL-1beta was comparable between the three groups but only detectable in cultures stimulated with lipopolysaccharide; it decreased in patients treated with prednisolone: 3.8 ng/10(6)monocytes (median) vs 11.7 (P=0.045). Release of IL-1ra was in all but IgG-stimulated cultures comparable between groups. The ratio of IL-1ra/IL-1beta was elevated in LPS-stimulated cells from RA patients only: 2.0 versus 1.3 (P=0.02). In contrast, IgG-induced IL-1ra release was significantly elevated only in non-RA patients: 95 ng/10(6)monocytes vs 40 (P=0.014), and the levels correlated positively to those of blood CRP (P=0.02). Though stimulated release of IL-10 was similar between the three groups, the levels were lower in non-erosive than erosive arthritis patients, and controls (P=0. 05). In conclusion, increased IgG-stimulated IL-1ra release and elevated IL-1ra/IL-1beta ratio may protect against actions of IL-1 in vivo, and decreased release of IL-10 might be related to features of non-erosive arthritis.

Adult↗
PubMed2000

Increased hepatocyte turnover and inhibition of woodchuck hepatitis B virus replication by adefovir in vitro do not lead to reduction of the closed circular DNA.

The aim of this study was to evaluate the inhibitory effect of the nucleotide analogue adefovir on woodchuck hepatitis B virus (WHV) replication and, in particular, to determine whether the pool of covalently closed circular DNA (cccDNA) could be reduced by adefovir treatment in primary cultures of woodchuck hepatocytes isolated from a chronic carrier. Strong reduction of WHV-DNA synthesis (90%) and secretion (up to 98%) was observed with all 3 doses of adefovir used (1, 10, and 100 micromol/L), whereas in the absence of the drug, high amounts of viral particles were continuously secreted in the culture medium until the end of the study (27 days). Secretion of envelope proteins and viral RNA levels remained constant both in the adefovir-treated and -untreated cultures for the entire course of the study. Intracellular core protein levels declined by approximately 50% in all the cultures, independent of adefovir treatment. There was no indication of cccDNA loss in the adefovir-treated hepatocyte cultures even when cell turnover was induced for 14 days by the addition of epidermal growth factor (EGF) to the culture medium. Our data show that adefovir has a very strong inhibitory effect on WHV-DNA synthesis in chronically infected primary hepatocyte cultures and indicate that cccDNA is a very stable molecule that appears to be efficiently transmitted to the dividing hepatocytes.

Adenine↗
PubMed2000

The release of nickel and other trace elements from electric kettles and coffee machines.

The release of nickel, chromium and lead from electric kettles to water under conditions simulating regular household use was investigated. Ten out of 26 kettles sold on the Danish market released more than 50 micrograms/l nickel to water, whereas neither lead nor chromium was released in any significant amount. Fifty micrograms/l of nickel in water was chosen as the threshold of action, because concentrations below this value were considered unlikely to provide outbreaks of eczema for those consumers suffering from contact allergy to nickel, who are also sensitive to the content of nickel in the diet. This first part of the study was followed up by a dialogue between the kettle producers and the Danish authorities, leading to a change of construction or design for those kettles that did not comply with the criteria. As a follow-up study another ten kettles were studied to check whether compliance was improved. Two of these ten kettles still released more than 50 micrograms/l nickel to water under the test conditions. These two kettles, however, were subsequently withdrawn from the market. Coffee machines tested similarly did not release aluminium, lead, chromium or nickel in quantities of any significance.

Chromium↗
PubMed2000

A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature.

OBJECTIVE: To test the usefulness of the Chapel Hill nomenclature, supplemented with surrogate parameters, as diagnostic criteria for primary vasculitides. METHODS: To prospectively evaluate vasculitis patients according to a standardised clinical and para-clinical programme. In accordance with the Chapel Hill publication surrogate parameters were used: proteinuria, haematuria and red blood cell casts (glomerulonephritis), angiographic or ultrasonic demonstration of aneurysms or stenoses (arteritis), radiological lung infiltrates or cavitations of more than one month's duration (granuloma in the lungs), bloody nasal discharge or crusts, chronic sinusitis, otitis and/or mastoiditis, bone and/or cartilage destruction, and acute hearing loss (granuloma in upper airways). RESULTS: The following entities were diagnosed: giant cell arteritis (n=14), Takayasu arteritis (n=1), polyarteritis nodosa (n=2), Wegener's granulomatosis (n=27), Churg-Strauss syndrome (n=2), microscopic polyangiitis (n=12), Henoch-Schönlein purpura (n=2), cutaneous leucocytoclastic angiitis (n=37), and secondary vasculitis (n=21). Giant cell arteritis and cutaneous leucocytoclastic angiitis were in all cases diagnosed by biopsy. Using the Chapel Hill nomenclature supplemented with surrogate parameters, only 8 of 27 patients were diagnosed with Wegener's granulomatosis, and 3 of 12 cases with microscopic polyangiitis. The number of patients in the remaining diagnostic entities were considered to few to evaluate. CONCLUSIONS: The Chapel Hill nomenclature, supplemented with surrogate parameters, failed to act as diagnostic criteria in Wegener's granulomatosis and microscopic polyangiitis. The following diagnostic criteria are proposed for Wegener's granulomatosis: (1) Biopsy or surrogate parameter for granulomatous inflammation in the respiratory system and (2) Biopsy verified necrotising vasculitis in small to medium sized vessels or biopsy/surrogate parameter for glomerulonephritis or positive PR3-ANCA test and (3) Lack of eosinophilia in blood and biopsy samples. The following diagnostic criteria are proposed for microscopic polyangiitis: (1) Biopsy verified necrotising vasculitis in small vessels and/or glomerulonephritis with few or no immune deposits and (2) Involvement of more than one organ system as indicated by biopsy verified vasculitis in small to medium sized vessels or surrogate parameter for glomerulonephritis and (3) Lack of biopsy and surrogate parameter for granulomatous inflammation in the respiratory system. Using these criteria all Wegener's patients and 9 of 12 patients with microscopic polyangiitis could be diagnosed.

Adolescent↗
PubMed2000

Two edged role of mannose binding lectin in rheumatoid arthritis: a cross sectional study.

OBJECTIVE: We investigated whether polymorphisms in the gene of mannose binding lectin (MBL) may be associated with onset of rheumatoid arthritis (RA), and whether MBL in conjunction with aggregated agalactosyl IgG (IgG-G0) may be associated with clinical and paraclinical variables. METHODS: MBL genotypes and serum concentrations were measured by polymerase chain reaction and ELISA in 189 patients with established RA. Binding of purified MBL to IgG-G0 in serum was assessed and clinical and paraclinical variables were recorded. RESULTS: The median age at onset of RA in the 3 genotypes (normal: A/A, hetero: A/0, and homozygous: 0/0 for variant alleles) was 54.1 (n = 108), 47.0 (n = 68), and 38.4 years (n = 13), respectively (p = 0.01). The frequency of variant alleles in patients with onset below the median age (50.8 yrs) was 0.32, but was 0.17 in patients with onset above 50.8 years (p = 0.003) and 0.20 in 250 controls (p = 0.001). Stratification according to erosion score (no, small, large) revealed an increasing tendency among the different groups in binding of MBL to IgG-G0, increased Health Assessment Questionnaire score, and acute phase reactants in A/A individuals, while no difference was seen among carriers of variant alleles. This effect was most pronounced in those with late onset RA. CONCLUSION: Presence of MBL variant alleles was associated with early onset of RA. MBL deficiency may, therefore, accelerate the disease. However, in patients with late onset and advanced disease our results indicate that the A/A type may be associated with additional inflammation different from that seen in carriers of variant alleles.

Adult↗
PubMed1999

Insulin in oral immune "tolerance": a one-amino acid change in the B chain makes the difference.

Oral administration of self-Ags can dampen or prevent autoimmune processes by induction of bystander suppression. Based on encouraging results from experiments in nonobese diabetic (NOD) mice, clinical trials have been initiated in type 1 diabetes using human insulin as an oral Ag. However, neither the precise antigenic requirements nor the mechanism of bystander suppression are currently understood in detail. Here we report that 1) a 1-aa difference in position 30 of the insulin B chain abrogated the ability of insulin to confer protection in both NOD as well as a virus-induced transgenic mouse model for type 1 diabetes. In the latter model transgenic mice express the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promotor (RIP) in the pancreatic beta cells and develop diabetes only following LCMV infection; and 2) protection could be transferred with insulin B chain-restimulated but not LCMV-restimulated splenocytes from RIP-NP transgenic mice, demonstrating that the mechanism of diabetes prevention in the RIP-NP model is mediated by insulin B chain-specific, IL-4-producing regulatory cells acting as bystander suppressors.

Administration, Oral↗
PubMed1999

Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis.

We targeted expression of human/fly chimeric Bcr-Abl proteins to the developing central nervous system (CNS) and eye imaginal disc of Drosophila melanogaster. Neural expression of human/fly chimeric P210 Bcr-Abl or P185 Bcr-Abl rescued abl mutant flies from pupal lethality, indicating that P210 and P185 Bcr-Abl can substitute functionally for Drosophila Abl during axonogenesis. However, increased levels of neurally expressed P210 or P185 Bcr-Abl but not Drosophila Abl produced CNS defects and lethality. Expression of P210 or P185 in the eye imaginal disc produced a dominant rough eye phenotype that was dependent on dosage of the transgene. Drosophila Enabled, previously identified as a suppressor of the abl mutant phenotype and substrate for Drosophila Abl kinase, had markedly increased phosphotyrosine levels in Bcr-Abl expressing Drosophila, indicating that it is a substrate for Bcr-Abl as well. Drosophila, therefore, is a suitable model system to identify Bcr-Abl interactions important for signal transduction and oncogenesis.

Animals↗
PubMed1999

Mannose-binding lectin polymorphisms and susceptibility to infection in systemic lupus erythematosus.

OBJECTIVE: To determine whether variant alleles in the coding portion of the mannose-binding lectin (MBL) gene are associated with increased susceptibility to systemic lupus erythematosus (SLE) and concomitant infections. METHODS: MBL alleles and serum concentrations were determined by polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in 91 Danish patients with SLE and in 250 controls. RESULTS: Homozygosity for MBL variant alleles was observed in 7.7% of the SLE patients compared with 2.8% of the controls (P = 0.06), while no difference was seen for heterozygosity (33.0% versus 34.4%). Homozygotes had an increased risk of acquiring serious infections compared with patients who were heterozygous or homozygous for the normal allele (odds ratio 8.6, 95% confidence interval 1.5-47.6, P = 0.01). The time interval from the diagnosis of SLE to the first infectious event was shorter (P = 0.017), and the annual number of infectious events was 4 times higher, among homozygotes (P = 0.00002). They were especially prone to acquire pneumonia (P = 0.00004). CONCLUSION; Homozygosity for MBL variant alleles may explain much of the increased risk of complicating infections seen in SLE patients. Additionally, it is a minor risk factor for acquiring SLE.

Adolescent↗
PubMed1999

Influence of Three Contrasting Detrital Carbon Sources on Planktonic Bacterial Metabolism in a Mesotrophic Lake.

Abstract Lakes receive organic carbon from a diversity of sources which vary in their contribution to planktonic microbial food webs. We conducted a mesocosm study to test the effects of three different detrital carbon sources (algae, aquatic macrophytes, terrestrial leaves) on several measures of microbial metabolism in a small meso-eutrophic lake (DOC approximately 5 mg/L). Small DOC additions (DeltaC < 1 mg/L) affected bacterial numbers, growth, and pathways of carbon acquisition. Macrophyte and leaf detritus significantly increased TDP and color, but bacterial densities initially (+12 h) were unaffected. After 168 h, densities in systems amended with terrestrial detritus were 60% less than in controls, while production rates in mesocosms with macrophyte detritus were 4-fold greater. Detritus treatments resulted in greater per-cell production rates either through stable cell numbers and greater growth rates (macrophyte-C) or lower densities with stable production rates (terrestrial-C). After only 12 h, rates of leucine aminopeptidase (LAPase) activity were 2.5x greater in macrophyte-C systems than in controls, but LAPase and beta-N-acetylglucosamindase activities in systems amended with terrestrial-C were only 50% of rates in controls. After 168 h, beta-xylosidase rates were significantly greater in communities with terrestrial and phytoplankton detritus. Microbial utilization of >20% of 102 carbon sources tested were affected by at least one detritus addition. Macrophyte-C had positive (6% of substrates) and negative (14%) effects on substrate use; terrestrial detritus had mainly positive effects. An ordination based on carbon-use profiles (+12 h) revealed a cluster of macrophyte-amended communities with greater use of psicose, lactulose, and succinamic acid; controls and algal-detritus systems were more effective in metabolizing two common sugars and cellobiose. After 168 h, communities receiving terrestrial detritus were most tightly clustered, exhibiting greater use of raffinose, pyroglutamic acid, and sebacic acid. Results suggest that pelagic bacterial communities respond to changes in organic carbon source rapidly and by different routes, including shifts in per-cell production rates and variations in degradation of a variety of compounds comprising the DOC pool.

Journal Article↗
PubMed1999

[Lipid intervention and coronary heart disease in men less than 56 years of age. The Coronary Intervention Study: CIS].

UNLABELLED: The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 x 4 g Colestyramin), and diet counselling. Male patients, average age 49 (< or = 56) years, were included with angiographic CAD and a screening total cholesterol of 207-350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, who did not suffer from serious other disease (e.g., diabetes mellitus), and who had not undergone coronary bypass surgery previously. RESULTS: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of -35%, in Apo-Protein B (ApoB) of -30%, in VLDL-C of -37%, and in triglycerides (TG) of -27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: -41, -36, -39, -31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by -0.017; P: -0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: -0.20; P: +0.23 mm; p = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to four-times less in the S group as compared to the control group (S: by 0.69%; P: by 2.73%; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; p < 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis "as treated". The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronounced in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12-56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C gr

Anticholesteremic Agents↗
PubMed1999

Silicone venous access devices positioned with their tips high in the superior vena cava are more likely to malfunction.

BACKGROUND: Silicone venous access devices (VADs) are commonly used for multiple intravenous infusions and blood sampling in chronically ill patients, particularly cancer patients. These devices are susceptible to malfunctions most commonly characterized by difficulty infusing fluids or withdrawing blood. We hypothesized that the incidence of such malfunctions is primarily related to the position of the catheter tip relative to the superior vena cava/right atrial junction. METHODS: We reviewed medical records for 141 patients in whom silicone venous access devices were used. Chest radiographs obtained following catheter insertion were reviewed by a single radiologist to rule out pneumothorax and determine the position of the catheter tip. Other potential factors included in the analysis were catheter brand, the vein into which the catheter was inserted, and the side (right or left). A malfunction was defined as resistance to flushing or infusion of a substance, complete inability to infuse a substance, resistance to blood aspiration attempts, or absence of blood return with aspiration, occurring any time during which the catheter was in place. Multiple logistic regression was used to determine which factor(s) most strongly predicted catheter malfunction. RESULTS: Catheter tip location was the only factor that was statistically predictive of malfunctions (coefficient 0.842, P < 0.001). A significant increase in malfunctions was observed in cases where the catheter tip was located greater than 4 cm superior to the junction of the right atrium and the superior vena cava (z-test of proportions, P = 0.003). Malfunctions were minimized in those cases where the catheter tip was located in the right atrium. CONCLUSIONS: These results indicate that malfunctions can be minimized in silicone venous access catheters by locating the catheter tip as close to the superior vena cava/right atrial junction as possible, or slightly inside the right atrium. To ensure proper location of the catheter tip, placement should be performed under fluoroscopy, and a radiograph should be obtained immediately following placement, with the patient in the upright position.

Catheterization, Central Venous↗
PubMed1999

Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL-4/Stat6 pathway.

Targeted immune regulation can be achieved by use of tissue-specific T cells and offers the potential for organ-specific suppression of destructive autoimmune processes. Here, we report the generation and characterization of insulin B chain-specific "autoreactive" CD4+ regulatory T cells that locally suppress diabetogenic T cell responses against an unrelated self-antigen (viral transgene) in a virus-induced model for type 1 diabetes. Interleukin 4 (IL-4) is essential for prevention of diabetes since regulatory T cells cannot be induced in the absence of IL-4 or stat6 (IL-4 signaling pathway). Our observations demonstrate that autoreactive regulatory T cells can suppress autoreactive destructive T cell activity of differential antigenic specificity locally in the pancreatic draining lymph node, probably via cytokine-mediated modulation of antigen-presenting cells.

Administration, Oral↗