Facilitators and barriers to TB care during the COVID-19 pandemic.

BACKGROUND: Knowledge about factors influencing access and adherence to TB care, and on the impact of the COVID-19 pandemic on TB care in resource-restricted settings is scarce. We conducted this study in Atsimo-Andrefana, a rural region in southern Madagascar where TB prevalence, poverty and food insecurity rates are high. We aimed to determine facilitators and barriers to access to and provision of TB care in rural Madagascar during the COVID-19 pandemic. METHODS: We conducted qualitative focus group discussions (FGDs) and in-depth interviews (IDIs) with patients with TB, community health workers, facility-based health workers, public health officials and non-governmental organisation staff. We analysed interviews using thematic analysis. RESULTS: We conducted 11 FGDs and 23 IDIs. We identified three main barriers to access and adherence to TB care: 1) stigma, 2) indirect treatment costs, and 3) food insecurity. The facilitator perceived as most influential was high health worker motivation. The effects of the COVID-19 pandemic on TB care varied between stake-holders; some health workers described delays in TB diagnosis and increased workload. CONCLUSIONS: To improve access and adherence to TB care, both indirect treatment costs and stigma need to be reduced; undernourished patients with TB should receive food support.

CONTEXTE: Les connaissances sur les facteurs influençant l'accès et l'adhésion aux soins antituberculeux, ainsi que sur l'impact de la pandémie de COVID-19 sur les soins antituberculeux dans les milieux à ressources limitées sont rares. Nous avons mené cette étude à Atsimo-Andrefana, une région rurale du sud de Madagascar où la prévalence de la TB et les taux de pauvreté et d'insécurité alimentaire sont élevés. Nous avons cherché à déterminer les facilitateurs et les obstacles à l'accès et à la fourniture de soins antituberculeux dans les zones rurales de Madagascar pendant la pandémie de COVID-19. MÉTHODES: Nous avons mené des discussions qualitatives en groupe (FGD) et des entretiens approfondis (IDI) avec des patients atteints de tuberculose, des agents de santé communautaires, des agents de santé en établissement, des responsables de la santé publique et des membres d'organisations non gouvernementales. Nous avons analysé les entretiens en utilisant l'analyse thématique. RÉSULTATS: Nous avons mené 11 FGD et 23 IDI. Nous avons identifié trois principaux obstacles à l'accès et à l'observance des soins antituberculeux : 1) la stigmatisation, 2) les coûts indirects du traitement et 3) l'insécurité alimentaire. Le facilitateur perçu comme le plus influent était la forte motivation des agents de santé. Les effets de la pandémie de COVID-19 sur les soins antituberculeux varient selon les parties prenantes ; certains agents de santé ont décrit des retards dans le diagnostic de la TB et une augmentation de la charge de travail. CONCLUSIONS: Pour améliorer l'accès et l'adhésion aux soins antituberculeux, il faut réduire à la fois les coûts indirects du traitement et la stigmatisation ; les patients tuberculeux sousalimentés devraient recevoir une aide alimentaire.

Short-term efficacy of tacrolimus in steroid-refractory ulcerative colitis - experience in 130 patients.

BACKGROUND: Steroid-refractory ulcerative colitis (UC) remains a challenging condition warranting surgery upon failure of pharmacological treatment. Calcineurin inhibitors or infliximab are alternatives in this situation. Data on the efficacy and safety of tacrolimus in this setting are limited. AIM: To study the short-term efficacy and safety of tacrolimus in moderate-to-severe steroid-refractory UC. The role of thiopurines in this situation and predictors of colectomy were evaluated. METHODS: In three centers, all charts from tacrolimus-treated patients with steroid-refractory UC were reviewed. Efficacy was assessed by colectomy-free survival and clinical remission at 3 months. RESULTS: We identified 130 patients with pancolitis in 75 (59%), left-sided disease in 35 (27%) and proctitis in 18 patients (14%) (disease localisation not obtainable in two patients). The median age was 40 (range: 18-81). Clinical activity according to the median Lichtiger score decreased from 13 (range: 4-17) at baseline to 3 (0-14) at week 12. Eighteen patients underwent colectomy within the first 3 months of treatment with tacrolimus (14%). Clinical remission was achieved in 94 patients (72%) in this period. Thiopurines given in parallel to tacrolimus tended to limit colectomy and significantly increased remission (P = 0.002) in the short-term. No other predictors of colectomy or remission were identified. Side effects were noticed in 53% of patients and no severe events occurred. CONCLUSION: This large survey confirms the efficacy and safety of tacrolimus in patients with steroid-refractory ulcerative colitis.

Inflammation and immunity in the tumor environment.

The relationship between inflammation, innate immunity and cancer is widely accepted. Cancer-associated inflammation includes infiltrating leukocytes, cytokines, chemokines, growth factors, lipid messengers and matrix-degrading enzymes. Tumor-associated macrophages and lymphocyte subpopulations are major components of the leukocyte infiltrate in most tumors. However, the cytokine and chemokine expression profile of the tumor microenvironment may be more relevant than its specific immune cell content. Apart from inflammatory cells, tumor stroma consists of new blood vessels and connective tissue. Many factors produced by tumor cells promote tumor angiogenesis and generation of extracellular matrix. Investigations regarding the link between inflammation and cancer are vital for identifying cell or protein targets for cancer prevention and therapy. Based on the relation between inflammation and cancer, different forms of immunotherapy have been developed. In a mouse model, we investigated the potential of Streptococcus pyogenes to achieve a bacteria-related immune response against tumor cells followed by tumor regression. As a model of pancreatic carcinoma, the aggressively growing and poorly immunogenic Panc02 tumor model was chosen. Our findings showed that a local application of bacteria mediates complete tumor regression. Future investigations should focus on the optimization of immunotherapeutic approaches that incorporate live bacteria or bacterial components.

3D CT evaluation of common crus aplasia.

Aplasia of the common crus is an uncommon congenital anomaly. We present the case of a patient with common crus aplasia and discuss the relevant embryology and the role of 3D CT in evaluation of this rare congenital anomaly.

Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model.

BACKGROUND: This study addressed the potential of bacteriolytic therapy using Streptococcus pyogenes in a syngeneic pancreatic carcinoma mouse model. METHODS: Panc02 tumours were either infected with S pyogenes or were treated with the equivalent volume of vehicle. In addition to assessment of tumour histology and immunohistochemistry, isolated splenocytes were analysed by flow cytometry. Interferon (IFN) gamma secretion as a reaction of splenocytes against tumour cells was shown through the ELISpot technique. A cytotoxic effect of lymphocytes against tumour targets was detected by lactate dehydrogenase (LDH) release. Cytokine levels in serum were measured. RESULTS: A single application of live bacteria into established Panc02 tumours resulted in complete tumour regression. This antitumoral effect was accompanied by massive leucocyte infiltration into the tumours as well as a significant and sustained elevation of systemic levels of the proinflammatory cytokines IFN gamma, tumour necrosis factor alpha and interleukin 6. Lymphocytes obtained from treated mice specifically recognised syngeneic tumour cells in IFN gamma-ELISpot, and most importantly in cellular cytotoxicity assays, indicating a tumour-specific immune response. CONCLUSIONS: We provide data that both the direct lytic activity of S pyogenes towards tumour cells and the infection-driven infiltration of tumours by cells of the innate immune system lead to damage of tumour cells followed by a dissemination of tumour components. This last outcome allows for the activation of tumour-specific effector cells, most probably in draining lymph nodes, promoted by the proinflammatory context. Taken together, these data indicate that the application of live S pyogenes may be a promising new treatment strategy for advanced pancreatic cancer patients that warrants further investigation.

[Prophylactic splenectomy for splenic vein thrombosis in patients undergoing resection for chronic pancreatitis]. / Prophylaktische Splenektomie während Resektion bei chronischer Pankreatitis.

AIM: Chronic pancreatitis (CP) is the leading cause of splenic vein thrombosis (SVT). SVT occurs in about 15 % of patients with CP. The risk of variceal bleeding in SVT is approximately 10 %. Splenectomy is indicated in symptomatic SVT but its role in asymptomatic SVT is discussed controversially. Aim of our study was to evaluate the outcome of splenectomy performed during pancreatic resection in patients with CP and asymptomatic SVT. METHODS: 33 of 198 patients undergoing resection for CP underwent concomitant prophylactic splenectomy for asymptomatic SVT. Perioperative data were compared in the groups of patients with or without splenectomy. Follow-up was complete in 84 % (average 31 months). RESULTS: Median operative time, postoperative morbidity, reoperation rate and mortality were not different in patients with or without splenectomy. The median number of blood units transfused was higher in patients with prophylactic splenectomy (6 vs 4 units; p < 0.01). One complication of splenectomy (postoperative bleeding) occurred (3 %). During follow-up no variceal bleeding, no episode of postsplenectomy sepsis or thrombosis due to temporary thrombocytosis occurred. CONCLUSIONS: Complications of prophylactic splenectomy are rare and less frequent than reported episodes of variceal bleeding. In the presence of asymptomatic SVT splenectomy should be considered during pancreatic resection to facilitate surgery and to avoid further variceal bleeding.

Extracellular signal regulated kinases are key mediators of mitogenic signals in rat pancreatic stellate cells.

BACKGROUND: Pancreatic stellate cells (PSCs) have been implicated in pancreatic fibrosis as they synthesise increased amounts of extracellular matrix proteins in response to activation by profibrogenic mediators such as cytokines. AIMS: The purpose of this study was to analyse cytokine receptor stimulated signalling pathways involved in PSC activation. Using a rat culture model of PSCs, we have also tested the potential of the platelet derived growth factor (PDGF) antagonist trapidil and PD98059, a specific inhibitor of extracellular signal regulated kinase (ERK) activation, to suppress PSC growth. METHODS: Cultured PSCs were stimulated with PDGF, and the signal transduction pathways activated in response to the mitogen were analysed by immunoblotting, kinase assays, and electrophoretic mobility shift assays. Furthermore, comparison of signalling cascades activated in PSCs before and after completing transdifferentiation to alpha-smooth muscle actin expressing myofibroblasts was performed. Biological effects of PDGF, trapidil, and PD98059 were analysed by proliferation assays and correlated with molecular effects of the substances. RESULTS: PDGF induced rapid activation of Raf-1, ERKs 1 and 2, as well as AP-1 proteins. The transforming growth factor beta activated transcription factor Smad2 was found to be constitutively phosphorylated in PSCs of different transdifferentiation grades. Furthermore, the results indicate a correlation between ERK activities and induction of PSC activation. Trapidil efficiently inhibited both PDGF induced ERK activation and, in common with PD98059, PSC proliferation. CONCLUSIONS: Our data suggest that ERKs play a key role in the regulation of PSC growth and that inhibition of the ERK signalling pathway may become a strategy to prevent activation of these cells.

Expression of hepatocyte growth factor, keratinocyte growth factor and their receptors in experimental chronic pancreatitis.

BACKGROUND: Hepatocyte (HGF) and Keratinocyte growth factors (KGF) are key factors of tissue organization and regeneration. These peptide growth factors and their receptors c-met and keratinocyte growth factor receptor (KGFR) are overexpressed in pancreatic cancer. AIM: Expression and localization of ligands and receptors were investigated during the development of experimental chronic pancreatitis. METHODS: Chronic pancreatitis was induced in rats by intravenous injection of dibutyltin dichloride. One to 60 days after treatment, the expression of growth factors and receptors was analysed by competitive polymerase chain reaction, Western blot analysis and immunohistochemistry. RESULTS: HGF mRNA expression increased (10-fold) until days 7-14 followed by a decrease to control level. Expression of c-met mRNA constantly increased (15-fold). KGF and KGFR mRNA expression were increased after 14-28 days (5-fold) and then returned to control levels. mRNA expression patterns correlated with changes in the protein expression, whereas protein levels of KGF remained unchanged. Ligands were localized in mesenchymal cells and their receptors on epithelial cells. CONCLUSIONS: The significant increase of HGF and c-met expression suggests an essential role of this growth factor in the morphological changes during the development of chronic pancreatitis. Changes in the expression of KGF and KGFR are less pronounced.

Cytokine mRNA levels and lymphocyte infiltration in pancreatic tissue during experimental chronic pancreatitis induced by dibutyltin dichloride.

There is little information available regarding the role of inflammatory cells in the pathogenesis of chronic pancreatitis. Therefore, we analyzed the local cytokine profile and infiltrating lymphocytes in a rat model of chronic pancreatitis. Experimental pancreatitis was induced by a single intravenous application of dibultyltin dichloride (DBTC). During a time course of two months we observed the mRNA expression of cytokines using competitive RT-PCR. Lymphocytes were characterized by immunohistochemistry, FACS analysis, and the lymphocyte proliferation test. IL-1beta, IL-6, IL-5, and IL-10 were immediately up-regulated in the acute phase of disease, while lymphocyte-restricted expression of IL-2, IL-2R, and IFN-y was only found in the chronic course. Among the infiltrating lymphocytes, CD4+ cells dominated, but during the chronic process there was an increase of CD8+ cells, resulting in a reduced CD4/CD8 ratio. Mitogen-induced activation of isolated mesenteric lymph node cells increased during the chronic inflammation. Our results suggest that in experimental pancreatitis acute inflammatory reactions are followed by a T-lymphocyte-mediated process.

Estradiol has a direct impact on the exocrine pancreas as demonstrated by enzyme and vigilin expression.

BACKGROUND: Estrogen receptors have been found in the exocrine pancreas; however, the exact role of estrogen in pancreatic enzyme synthesis and secretion remains to be elucidated. Vigilin, a multi-KH domain protein, is part of a tRNA-containing ribonucleoprotein complex and may be a suitable marker for stimulation of the translational machinery. In the present study, we investigated the influence of estradiol and compared it to CCK on the expression of vigilin, trypsin and amylase in rat pancreatic acini. METHODS: Acini were isolated and incubated with CCK or estradiol. The change in amylase and trypsin levels in the medium and in cell extracts were determined using a photometric method. The change in vigilin mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. RESULTS: Treatment of isolated exocrine pancreatic cells with estradiol caused stimulation of amylase and trypsin production and inhibition of secretion, while treatment with CCK showed only a minor effect on enzyme production and resulted mainly in a stimulation of secretion. Further we found an increase in vigilin mRNA and protein expression in acini stimulated with both CCK-8 and estradiol. CONCLUSION: Our data suggest that estradiol may play a role in inducing exocrine enzyme production but not secretion, and that vigilin, as a marker for translational activity, is stimulated in parallel to the pancreatic enzymes: amylase and trypsin.

Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.

In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns. MARS enables the selective removal of albumin-bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk (bilirubin level, > or =15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child-Turcotte-Pugh scores of 12.4 +/- 1. 0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 +/- 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 +/- 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels (P <.01) and increase in serum sodium level and prothrombin activity (P <.01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively (P <.01). We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS.

Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group.

The chimeric anti-TNF antibody Remicade (Infliximab) has recently been approved for human use by the FDA and is now available on the market. Since there is considerable interest in this kind of treatment among patients with Crohn's disease, an international working group has summarized the presently available information about efficacy, side effects and possible problems of this treatment. Studies show that Remicade is effective in the treatment of active Crohn's disease, maintaining remission and fistulae. The working group does not see Infliximab as a first-line treatment for Crohn's disease. It may be used in active phase recurrent disease, chronic active disease and fistulae if standard treatment was not successful. For the surveillance special attention has to be given to the unknown malignancy rate of Infliximab. Infusion should be performed in an institution, routinely performing intravenous infusions and a two-hour surveillance of the patients should be guaranteed to recognize anaphylactic reactions or acute side effects. There is presently no information indication that the combination with immunosuppressants might increase risks or side effects of this treatment. Due to the limited information available the working group would prefer to use Remicade in studies only and recommends central collection and documentation of all data on efficacy and side effects for the next year.

Release of hyaluronan and laminin into pancreatic secretions.

BACKGROUND: Development of fibrosis characterizes chronic pancreatitis. As it results from deposition of extracellular matrix (ECM) proteins such as hyaluronan (HA) or laminin, the release of these ECM components into blood or pancreatic secretion may be enhanced during the course of chronic pancreatitis. PATIENTS, MATERIAL AND METHODS: Using immunoassays for HA and laminin, the concentration for these ECM components was measured in pancreatic juice and serum samples from 20 patients with and 20 patients without chronic pancreatitis. Pancreatic calculi of varying size and weight obtained from 13 patients with chronic pancreatitis were also examined for the content of ECM components. Tissue samples from normal pancreas and those showing chronic pancreatitis were investigated immunocytochemically with an antibody to HA synthetase (HAS). RESULTS: After stimulation with secretin high levels of ECM components were found in the initial washout period in chronic pancreatitis patients as well as in controls. HA levels, however, were seen seven times higher in patients with chronic pancreatitis (mean +/- SEM; 734 +/- 301 vs. 95 +/- 15 microg/l; p < 0.01). Serum HA levels correlated with the duration of chronic pancreatitis and with the levels of HA in pancreatic juice. HA and laminin were detected in the supernatants of pancreatic calculi (laminin 0.70 +/- 0.30 U/l; HA 275 +/- 85 microg/l). Immunocytochemically, strong staining for HAS was found in the duct epithelium and in centroacinar cells of chronic pancreatitis specimens. CONCLUSION: Demonstration of increased amounts of HA in pancreatic juice of chronic pancreatitis patients stimulated with secretin suggests enhanced production of this ECM component in the chronically inflamed pancreas. The source of HA appears to be the pancreatic ductal epithelium.

Serum levels of extracellular matrix in acute pancreatitis.

BACKGROUND/AIMS: Elevated levels of serum markers of extracellular matrix, i.e., the amino-terminal procollagen-III-peptide, hyaluronic acid and laminin are found in various diseases. The study aims to examine a panel of these parameters in patients with acute pancreatitis and correlate them with the course and severity of the disease. METHODOLOGY: We prospectively examined the time-course of procollagen-III-peptide, hyaluronic acid and laminin in 24 consecutive patients with acute necrotizing (n = 13) or edematous (n = 11) pancreatitis. Patients with chronic pancreatitis with (n = 10) or without (n = 17) acute pain, and 6 patients in complete remission after an episode of acute pancreatitis as well as healthy individuals served as controls. In addition, serum levels of collagen VI and undulin were followed in 10 and 9 patients with acute necrotizing pancreatitis, respectively. RESULTS: The serum concentrations of procollagen-III-peptide, hyaluronic acid and laminin were significantly higher at the onset of acute necrotizing pancreatitis compared to edematous pancreatitis and the controls. They returned to almost normal levels during the course of the disease when the patient recovered, but remained elevated in patients with a lethal course. Laminin allowed us to discriminate between patients with necrotizing pancreatitis from all other forms of pancreatitis on admission (specificity 82%, sensitivity 92%, PPV 86%, NPV 90%). Collagen type VI levels were 2-3-fold higher in sera of patients with acute pancreatitis than in healthy controls, whereas the results for undulin were inconclusive. CONCLUSIONS: Since markers of matrix metabolism (especially laminin) are differently elevated in acute necrotizing versus edematous pancreatitis, we suggest that they might be used as parameters for the outcome.

Immunohistochemical characterization of the pancreatic cellular infiltrate in normal pancreas, chronic pancreatitis and pancreatic carcinoma.

BACKGROUND/AIMS: Chronic pancreatitis is histologically characterized by an extended fibrosis and infiltration of leukocytes. We intended to differentiate the infiltration to evaluate the inflammatory process. METHODS: Samples of tissues of normal pancreas (NP, n = 12), of chronic pancreatitis (CP, n = 7), and pancreatic tissues surrounding pancreatic carcinoma (CA, n = 7) were investigated by immunohistochemical staining using the APAAP technique. RESULTS: In normal pancreas, mononuclear cells (47.1 +/- 26.0 cells/mm2) were observed with a predominance of macrophages (56.3%) and T lymphocytes (31.3%) which were differentiated in CD8+ lymphocytes (9.3 +/- 7.2 cells/ mm2) and CD4+ lymphocytes (6.7 +/- 3.2 cells/mm2). Rarely, plasma cells (5.3%) and B lymphocytes (7.1%) could be detected. In pancreatic tissue of patients with CP and in CA there was a significant increase of mononuclear cells to 264.4 +/- 120.3 cells/mm2 and 284.3 +/- 67.8 cells/mm2, respectively. In both diseases percentages of T lymphocytes (CP: 50.5%; CA: 48.1%) were higher than in normal controls. CD4+/CD8+ ratio of 0.77 in CP and 0.82 in CA demonstrated a predominance of CD8+ cells compared to the peripheral blood. In NP and CA, nearly all T lymphocytes expressed CD45R0 identifying memory cells, while only 58% of T lymphocytes were CD45R0 positive in CP. CONCLUSION: Our data suggest that the investigated cases of CP were of a common inflammatory type rather than due to an autoimmunological reaction. CD8+ T lymphocytes were the predominant T cell subset in the inflammatory infiltrates in both CP and CA.

Secretory immunoglobulin A in pancreatic juice and pancreatic tissue of patients with chronic pancreatitis.

BACKGROUND: The predominance of secretory IgA (S-IgA) in intestinal secretions compared with blood is well established, but concentrations of this protein in pancreatic juice and its origin, especially in chronic pancreatitis, are unknown. AIMS: To investigate the role of S-IgA in chronic pancreatitis. PATIENTS: Twenty one patients with chronic pancreatitis (group I), three patients with proven malignancies (group II), and 12 patients without pancreatic disease (group III). METHODS: Pure human pancreatic juice was collected endoscopically in four fractions after consecutive stimulation with secretin and cholecystokinin (CCK). Samples were analysed for S-IgA, protein, trypsinogen, and proteolytic activity. RESULTS: The S-IgA level was significant increased in fraction 1 of pancreatic juice of group I (1210 (1411) ng/ml) compared with controls (33 (70) ng/ml). Protein concentrations and trypsinogen content were lower in group I than in the other groups. Proteolytic activity could be observed in 53% of all 133 pancreatic juice samples, but in 87% of fraction 1. In pancreatic tissue of three patients with chronic pancreatitis both IgA and secretory component were detected by immunohistology. Expression of the secretory component by human pancreatic epithelial cells was increased in patients with chronic pancreatitis compared with normal controls. The concentration of S-IgA in pancreatic juice did not correlate with the serum S-IgA level. In contrast, serum levels of S-IgA were decreased in patients with chronic pancreatitis. CONCLUSION: There are high levels of S-IgA in human pancreatic juice following chronic inflammation and a protective role is suggested for this immunoglobulin.

Production of trypsin by cells of the exocrine pancreas is paralleled by the expression of the KH protein vigilin.

Vigilin, a protein with a continuous series of 14 KH motifs, forms part of a multiprotein complex containing tRNA. Several lines of evidence have suggested that vigilin expression is enhanced in those cells which were actively engaged in protein synthesis. Accordingly, we show here by immunoelectronmicroscopy a close association of vigilin with the rough endoplasmic reticulum in rat pancreatic cells. Histological examination of these cells furthermore demonstrates the highest intensity of vigilin staining in the perinuclear, intranuclear, and basolateral regions where the endoplasmic reticulum is mainly amassed. In vivo challenge of starving rats fed prior to sacrifice raised in parallel the protein levels of both trypsin and vigilin when compared to unchallenged animals and was associated with enhanced expression of the vigilin gene. In contrast, in human and rat cell lines of pancreatic tumors with a constitutively high expression of vigilin no further stimulation by cholecystokinin treatment could be achieved. Our data provide circumstantial evidence that vigilin may play a crucial role in the ability of an organ, e.g., pancreas, to cope with the physiological demand to upregulate protein synthesis.