Is the polymerase chain reaction or cure of Helicobacter pylori infection of help in the differential diagnosis of early gastric mucosa-associated lymphatic tissue lymphoma?

PURPOSE: The differential diagnosis of early gastric mucosa-associated lymphatic tissue (MALT) lymphoma based on Helicobacter pylori gastritis may be difficult when lymphoepithelial lesions are not detected. The aim of the present study was to investigate the question whether the polymerase chain reaction (PCR) or cure of H pylori infection may be of help in this respect. PATIENTS AND METHODS: Twenty patients with suspected low-grade gastric MALT lymphomas were treated in a double-blinded, randomized, crossover trial with 2,250 mg of either amoxicillin or placebo, both in combination with omeprazole, for 14 days with the aim to cure H pylori infection. PCR was performed using primers specific for the CDR3 region to detect monoclonal B cells. RESULTS: In five of 20 patients, MALT lymphomas were finally diagnosed. Three of these five patients went into complete remission, while two were referred to surgery. In the 15 patients with gastritis, complete regression was observed in all cases. With respect to PCR, monoclonal bands were detected in all four of the analyzed lymphoma patients before histology showed lymphoma. In addition, monoclonal bands were found in three patients with gastritis. In the patients with gastritis and monoclonal PCR, complete regression took longer as compared with the remaining 12 patients with polyclonal PCR and gastritis (P = .0209). Successful H pylori eradication was associated with earlier diagnosis of the MALT lymphoma (P = .0237). CONCLUSION: CDR3-PCR may be of help in the differential diagnosis of early gastric MALT lymphoma. Furthermore, H pylori eradication may lead to earlier diagnosis.     

Recent progress in the management of malignant lymphoma

In this article recent lymphoma-related topics were reviewed. REAL classification, a new histopathological classification of lymphoid neoplasm, has been controversial in terms of clinical usefulness. However, mantle cell lymphoma in the classification has been well established as one histopathological entity, and considered an intermediate grade lymphoma in prognosis. In gastric MALT lymphoma, Helicobacter pylori might provide the antigenic stimulus for its growth. The eradication of H. pylori causes regression of MALT lymphoma, and anti-H. pylori treatment should be given for this type of lymphoma. The international prognostic index has made it possible to make a different therapeutic plan according to the risk group. The results of new therapies, such as purine nucleoside analogs for low grade B cell lymphoma and high dose chemoradiotherapy for high grade aggressive lymphoma, were reviewed.     

Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma

PURPOSE: Although most patients with primary gastric low-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma experience complete endoscopic and histologic remission after the cure of Helicobacter pylori infection, in many patients, the polymerase chain reaction (PCR) still detects monoclonal B cells in the gastric mucosa. The present study asked whether the lymphoma immunoglobulin VH (IgVH) sequences remained stable in patients with gastric MALT lymphoma after H pylori eradication. PATIENTS AND METHODS: Eight patients with stage EI disease treated with H pylori eradication were analyzed before and at different time points after the cure of the infection. After the amplification of IgVH genes from DNA extracted from gastric biopsy specimens, monoclonal PCR products were cloned and multiple clones (43 to 105) were sequenced per patient. RESULTS: Mutations were detected in all lymphoma VH sequences, which suggested germinal center or postgerminal center origin of the lymphoma B cells. In five of the eight patients, clonal heterogeneity was observed at diagnosis or during follow-up. Genealogical analysis of shared and unshared mutations showed that the process of somatic mutations was ongoing after H pylori eradication in four of the five patients who showed clonal instability. Ongoing mutations were observed in three of the four patients who completely responded to H pylori eradication, but in only one of the four patients who did not respond or who partially responded. CONCLUSION: In low-grade gastric MALT lymphomas, an ongoing process of somatic hypermutation and antigen selection can be detected after the therapeutic removal of the underlying stimulus H pylori. These data point to the relevance of yet unknown antigens that drive this disease. In addition, they challenge the view that these lymphomas may be cured solely by the eradication of H pylori.     

Orthopedic and interventional applications at low field MRI with horizontally open configuration. A review

Two monoclonal antibodies (MAbs), designated as H9 (IgG2a) and H20 (IgM), directed against heat-shock protein 60 (HSP60) of Helicobacter pylori strain TK1029 were established. Affinity-purified antigens cross-reacted in immunoblots with MAb H9 and MAb H20 respectively. These antigens also reacted with the 3C8 MAb previously established in this laboratory, which recognised Yersinia enterocolitica HSP60. By amino-acid sequence analysis, the N-terminal amino-acid sequence of the protein recognised by both H9 and H20 MAbs was confirmed as the amino-acid sequence of H. pylori HSP60 reported previously. Both MAbs reacted with nine strains of H. pylori in enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. In addition, MAb H9 reacted with extracts of other bacteria including H. mustelae, Pseudomonas aeruginosa, Vibrio cholerae, Serratia marcescens, Proteus mirabilis, Escherichia coli and Shigella sonnei. In contrast, MAb H20 reacted only with strains H. pylori. These results suggest that both the species-specific epitope recognised by MAb H20 and the common epitope recognised by MAb H9 exist on HSP60 of the bacterial cell. Both MAbs also reacted with the 60-kDa protein in the lysate of human gastric carcinoma (MKN45) cells. It was shown by immunohistochemical staining that gastric epithelial cells of four out of six biopsy specimens examined stained positively with MAb H20. These results suggest that there is a common epitope in H. pylori HSP60 and human gastric epithelial cells.     

Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity

Helicobacter pylori is involved in gastritis, gastric and duodenal ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Earlier studies already suggested a role for autoimmune phenomena in H. pylori-linked disease. We now report that lipopolysaccharides (LPS) of H. pylori express Lewis y, Lewis x, and H type I blood group structures similar to those commonly occurring in gastric mucosa. Immunization of mice and rabbits with H. pylori cells or purified LPS induced an anti-Lewis x or y or anti-H type I response, yielding antibodies that bound human and murine gastric glandular tissue, granulocytes, adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma cells. Experimental oral infections in mice or natural infection in humans yielded anti-Lewis antibodies also. The beta chain of gastric (H+,K+)-ATPase, the parietal cell proton pump involved in acid secretion, contained Lewis y epitopes; gastric mucin contained Lewis x and y antigenic determinants. Growth in mice of a hybridoma that secretes H. pylori-induced anti-Lewis y monoclonal antibodies resulted in histopathological evidence of gastritis, which indicates a direct pathogenic role for anti-Lewis antibodies. In conclusion, our observations demonstrate that molecular mimicry between H. pylori LPS and the host, based on Lewis antigens, and provide understanding of an autoimmune mechanism for H. pylori-associated type B gastritis.     

DNA methylation in mycobacteria: absence of methylation at GATC (Dam) and CCA/TGG (Dcm) sequences

The histopathology of low-grade primary gastric lymphoma re-capitulates the structure of Peyer's patches (mucosa-associated lymphoid tissue--MALT) rather than lymph nodes, characterised by an increased frequency of trisomy 3. Gastric B-cell lymphoma shows a favourable clinical behaviour, possibly as its growth appears to be influenced by a local antigen in the form of Helicobacter pylori. There is no lymphoid tissue in the normal stomach, but lymphoid tissue accumulates in gastric mucosa almost exclusively as a consequence of H. pylori infection, which has MALT characteristics, and H. pylori is found in over 90% of cases of gastric MALT lymphoma. Laboratory studies have shown that the growth of tumour cells from low-grade gastric lymphomas can be stimulated by H. pylori, and that the effect is strain-specific and mediated by contact-dependent help from H. pylori-specific T-cells. Cases of low-grade gastric lymphoma, when confined to the mucosa, may regress following eradication of H. pylori from the patient's stomach. It remains to be shown whether deeply penetrating or high-grade tumours will respond in the same way. Other outstanding questions relate to the optimum interval between eradication of H. pylori and final evaluation and expected duration of the response. Based on these laboratory and clinical findings it is possible to suggest a scheme for the pathogenesis of gastric MALT lymphoma.     

Helicobacter pylori infection and gastrointestinal lymphomas

Primary gastric lymphoma of the MALT (mucosa-associated lymphoid tissue) is nowadays considered a distinct entity with specific morphological, biological and clinical characteristics. In the pathogenesis of gastric MALT lymphoma, Helicobacter pylori infection plays an important conditioning role, In the case of low grade gastric lymphoma of stage E I, eradication of Helicobacter pylori offers a promising therapeutic option.     

Impaired male sexual development in perinatal Sprague-Dawley and Long-Evans hooded rats exposed in utero and lactationally to p,p''-DDE

The evolution of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a multi-stage process, comprising the sequential development of chronic H. pylori-associated gastritis, low grade and high grade lymphoma. The genesis of MALT lymphoma embodies the mechanisms of both physiological immune responses and the acquisition of genetic abnormalities. The tumour probably originates from an autoreactive MALT marginal zone B cell, which is generated during H. pylori infection. As a consequence of a genotoxic insult induced by H. pylori infection, the progenitor tumour cell may become genetically unstable and develop genetic abnormalities such as the t(11;18) translocation, trisomy three, c-myc and p53 mutations during a phase of expansion, which lead to partial transformation. With the growth help from H. pylori specific T cells, this abnormal B cell clone may undergo clonal expansion and gradually form a low grade MALT lymphoma. Additional genetic abnormalities including the t(1;14) translocation and other uncharacterised events could completely transform this abnormal B cell clone and result in escape from T cell dependency. Finally, further genetic events such as complete inactivation of the tumour suppressor genes p53 and p16, and possible activation of c-myc oncogene by translocation or other undetermined abnormalities can result in high grade transformation     

Chronic pancreatitis and neoplasia: correlation or coincidence

Renal biopsy specimens from patients with membranous nephropathy (MN) were studied using immunohistochemical labelling to clarify the aetiological significance of Helicobacter pylori antigen in this disease. Sixteen specimens were examined, from 7 male and 9 female MN patients. Renal specimens from patients with diabetic nephropathy and IgA nephropathy, and from autopsied patients without renal diseases were obtained as controls. Immunohistochemical labelling was performed using one polyclonal antibody and three monoclonal antibodies against H. pylori. Specimens from 11 of the MN patients revealed granular deposits along the glomerular capillary walls, which reacted positively with polyclonal antibody after trypsin pretreatment. None of the control specimens revealed positive labelling. The MN specimens showed no positive reaction with the primary antibody, which had been treated for immunoabsorption testing using sonicated H. pylori. We also determined H. pylori status in these MN patients histologically and/or serologically. Of the 11 patients whose glomeruli were positive for anti-H. pylori antibody, 7 were suitable for analysis, and all were regarded as positive for H. pylori infection. These results suggest that the presence of a specific antigen in the glomeruli of patients with MN and H. pylori infection may be involved in the pathogenesis of MN.     

Performance characteristics of an enzyme-linked immunosorbent assay for determining salivary immunoglobulin G response to Helicobacter pylori

We evaluated the salivary immunoglobulin G (IgG) immune response to Helicobacter pylori in 70 subjects by enzyme-linked immunosorbent assay (ELISA). Subjects with a positive H. pylori culture showed significantly higher titers of antibodies than subjects with no detectable H. pylori: the overall sensitivity and specificity of the test were 84 and 90%, respectively. The detection of salivary anti-H. pylori IgG antibodies may be considered as an alternative to serum IgG detection for ease of sample collection or when blood samples are not available in screening of patients with dyspepsia.     

Trends in state laws and regulations affecting nurse-midwives: 1995-1997

Increased epithelial cell proliferation is associated with an increased risk of gastric carcinoma. Helicobacter pylori infection is an established risk factor for gastric cancer and the organism has recently been classified as a group I carcinogen by an IARC working group. In this study, we describe differences in gastric epithelial cell proliferation between a H. pylori eradicated group (n = 21) and a not eradicated group (n = 8) after anti-H. pylori eradication therapy to show that increased cell proliferation is associated with H. pylori infection. H. pylori infection was determined by rapid urease test and immunohistochemical method with anti-H. pylori polyclonal antibody. Gastric epithelial cell proliferation was assessed using immunohistochemical method using Ki-67 monoclonal antibody. Ki-67 positive cells in H. pylori associated chronic active gastritis were observed in the glandular neck and the upper portion of foveolar epithelium. Patients who cleared their H. pylori infections showed a significant decrease of Ki-67 labeling index after therapy (0.73 +/- 0.10 vs. 0.48 +/- 0.08, p < 0.01). By contrast, Ki-67 labeling index before and after treatment in patients who remained positive for H. pylori showed no significant difference (0.78 +/- 0.08 vs 0.74 +/- 0.10, p > 0.05). These results indicate that H. pylori infection increases the proliferation of gastric foveolar epithelium, which is reduced by the eradication therapy. We suggest that anti-H. pylori eradication therapy can prevent mucosal cell proliferation to be closely associated with gastric carcinogenesis.     

Isolation of a cell surface component of Helicobacter pylori that binds H type 2, Lewis(a), and Lewis(b) antigens

BACKGROUND & AIMS: Individuals of blood group O and nonsecretors of ABO blood group antigens are more susceptible to peptic ulcers. The aim of this study was to determine if blood group antigens associated with group O or secretor status are epithelial cell receptors for Helicobacter pylori. METHODS: Bacterial binding and binding of monoclonal antibodies to H type 2, Lewis(a), and Lewis(b) to Kato III, buccal epithelial, and gastric mucosal cells were shown by flow cytometry. Bacterial outer membrane proteins eluted from H type 2, Lewis(a), or Lewis(b) were shown by polyacrylamide gel electrophoresis. RESULTS: Kato III and human epithelial cells bound each monoclonal antibody; O cells bound more anti-H type 2 (P < 0.05). Binding indices for H. pylori correlated with those for anti-H type 2 (P < 0.005) and anti-Lewis(b) (P < 0.001) but not anti-Lewis(a). A 61-kilodalton protein was eluted from H type 2, Lewis(a), or Lewis(b). CONCLUSIONS: Our results indicate that H type 2 is an important receptor for the 61-kilodalton bacterial adhesin, partly explaining increased susceptibility of individuals of blood group O to ulcers. Lewis(b) binds H. pylori more efficiently than Lewis(a). If these interactions occur in vivo, lack of Lewis(b) in mucosal fluids of nonsecretors may contribute to colonization by H. pylori.     

Intestinal anastomosis by use of the biofragmentable anastomotic ring: is it safe and efficacious in emergency operations as well?

OBJECTIVE: To determine the phenotype of naturally developing lymphomas in young ferrets. ANIMALS: 10 ferrets with lymphoma. PROCEDURE: Neoplastic tissues were graded histologically according to the National Cancer Institute's Working Formulation for non-Hodgkin's lymphoma and phenotype was determined by means of immunohistochemical staining. A polyclonal anti-human CD3 and a monoclonal anti-human CD79 antibody were used to classify the lymphomas in situ as T-cell or B-cell origin. Specificity of antibodies was determined by evaluating lymphoid tissue from normal ferrets in situ, which was confirmed by western blot analyses. RESULTS: All 10 ferrets had clinically aggressive tumors, irrespective of the phenotype. Nine ferrets had T-cell lymphoma that extensively involved the mediastinum. Remnants of thymic tissue, indicative of thymic origin, were identified in lymphoma of these 9 ferrets. One ferret had a B-cell multicentric lymphoma without involvement of the mediastinum. CONCLUSIONS: The majority of lymphomas in these young ferrets involved the mediastinum and were of T-cell phenotype. Impact for Human Medicine-There are many similarities between the lymphoma syndrome of ferrets and the condition documented for cats and children with lymphoma of the mediastinal area. CLINICAL RELEVANCE: Differential diagnoses for young ferrets with clinical signs of lethargy or respiratory distress should include T-cell lymphoma of the mediastinum.     

Identification of the sheep homologue of the monocyte cell surface molecule--CD14

An ovine monocyte/macrophage cell surface antigen was recognized by three mouse monoclonal antibodies (mAbs) VPM65, VPM66 and VPM67. These mAbs also reacted with bovine cells. The antibodies immunoprecipitated a single, glycosyl-phosphatidylinositol-linked polypeptide of M(r) 55,000 which, when deglycosylated, was reduced to M(r) 53,000. They reacted strongly with peripheral blood monocytes, alveolar macrophages and peripheral blood granulocytes, and weakly with afferent lymph dendritic cells. They also reacted with macrophages in many different tissues but were non-reactive with lymphocytes. Competitive flow cytometry shows that these three mAbs recognize the same or a closely related epitope of a single antigen. An antigen-specific capture ELISA using the anti-human CD14 mAb (TUK4) revealed that all four mAbs associate with the same antigen. These data demonstrate that the mAbs react with the ovine homologue of the lipopolysaccharide (LPS)-LPS binding protein receptor, CD14.     

Observations on the prevalence of trypanosomosis in small ruminants, equines and cattle, in relation to tsetse challenge, in The Gambia

Lipoprotein lipase (LPL) hydrolyses triglycerides in chylomicrons and in very low density lipoproteins. In this study, a new sensitive enzyme immunoassay, the dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA), for the quantification of immunoreactive LPL mass in biological specimens was developed. In the indirect sandwich DELFIA assay polyclonal anti-human or anti-bovine LPL IgGs were used as capture antibodies, monoclonal antibody (mAb) 5D2 and Eu(3+)-labelled goat anti-mouse IgG were used as detection antibodies. In the direct sandwich DELFIA assay, mAb 5D2 was used as capture and Eu(3+)-labelled mAb 5D2 as detection antibodies. Both purified bovine and human LPL proteins served as standards in the indirect and the direct DELFIA assay. Standard curves were linear between 0.1 and 1000 ng LPL/ml, assuring the sensitivity of the DELFIAs within this range. Mean values for immunoreactive LPL mass in normal individuals were found to be 40.3 +/- 14.4 ng/ml preheparin plasma and 334.1 +/- 71 ng/ml postheparin plasma. In patients affected with type I hyperlipoproteinemia 82.4 +/- 29.3 ng/ml (postheparin plasma) were determined. Coefficients of inter- and intra-assay variation were 4.3% and 6.2% on average. The correlation coefficient between the indirect and the direct DELFIA technique was 0.9694. The correlation coefficient between immunoreactive LPL mass (estimated by DELFIA) and LPL activity (estimated by the LPL activity assay) was 0.9345. Our data are consistent with the concept that LPL is active as a dimer. Dissociation of the LPL dimer into monomers is tightly coupled to both loss of immunoreactivity and enzyme activity of LPL.     

Antibodies against Helicobacter pylori were detected in the cerebrospinal fluid obtained from patients with Guillain-Barré syndrome

We examined the antibodies against Helicobacter pylori proteins in the cerebrospinal fluid (CSF) of 7 patients with Guillain-Barré syndrome (GBS). Crude H. pylori antigens, fractionated heat shock protein (HSP), and urease B (UB) from H. pylori antigens were separated by SDS-PAGE. With Western blot analysis, four of seven CSF samples had several IgG antibodies against H. pylori proteins, including HSP and UB. No cross reactivity against Campylobacter jejuni was observed. These antibodies may be involved in the immune responses of patients with GBS.     

Eradiction of H. pylori results in regression of B-cell low grade gastric MALToma with evident B-symptoms

Although it is well known that eradication of H. pylori may result in either complete or partial regression of low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma), it would be of clinical interest to determine whether the B-symptoms of patients with MALToma could be relieved by eradication of H. pylori. Here, we report on a 29 year-old female case with B-cell low-grade gastric MALToma with apparent B-symptoms. Her peripheral blood also disclosed large granular lymphocytes (LGL). The B-symptoms of this patient were quickly relieved within 2 weeks after starting an anti-H. pylori regimen; peripheral blood LGLs were clearly decreased as well. Complete regression of MALToma was determined 4 months after the anti-H. pylori regimen. Thereafter, the patient has been disease-free and in good general condition during a 2-year follow-up.     

Helicobacter pylori and non-Helicobacter pylori bacterial flora in gastric mucosal and tumour specimens of patients with primary gastric lymphoma

There is an association between Helicobacter pylori (H. pylori) and gastric mucosa-associated lymphoid tissue (MALT) and MALT lymphoma. Histologically, mainly non-specific stains are used to detect H. pylori, such as haematoxylin-eosin (HE) or modified Giemsa (MG). In this study, both a MG and a specific immunohistochemical stain (IMM) for H. pylori (Dako B471) were performed on sequential slides of resected material containing tumour and non-tumorous gastric mucosa from patients with primary gastric lymphoma (n = 52). Special attention was paid to the presence of non-H. pylori bacterial flora diagnosed by a positive MG (according to form and localization) and a subsequently negative IMM. On all slides, bacterial density was scored semiquantitatively (grades 0, 1, 2, 3). In total, 32 (61.5%) patients were H. pylori positive using IMM and 34 (65.4%) were non-H. pylori positive using MG. In 24 out of the 34 patients, the non-H. pylori flora consisted mainly of cocci in combination with rods in 15 patients, mostly in minor quantities; in another 10 patients, high numbers of both cocci and different types of rods were present. Most non-H. pylori bacteria were localized superficially, although in 22 patients minor quantities of non-H. pylori were also seen in the glandular lumina. After all of the patients had been analysed, no differences in the density of H. pylori and of non-H. pylori flora were found. Only when comparing patients who had a small-cell lymphoma with those who had a large-cell lymphoma was a significantly higher density of H. pylori found in the corpus mucosa of large-cell lymphomas and a higher prevalence of non-H. pylori was found in tumours, in antrum or corpus, of patients with large-cell lymphomas. In conclusion, with joint evaluation using MG and a H. pylori-specific immunohistochemical stains, the proportion of H. pylori-positive gastric lymphoma patients was lower than in most previous studies but other bacteria were found in a relatively high proportion. The role of the non-H. pylori intragastric bacterial flora identified in this study has to be further elucidated in the aetiopathogenesis of primary gastric lymphoma.     

The Trp64Arg mutation of the beta3-adrenergic receptor is associated with hyperglycemia and current body mass index in Jamaican women

Helicobacter pylori is a major etiologic agent in gastroduodenal disorders. In this study, immunoglobulin A (IgA) antibodies to H. pylori antigens were evaluated in serum and gastric juice specimens obtained from patients with gastritis or peptic ulcers by utilizing antibody capture enzyme-linked immunosorbent assays (ACELISAs). Urease alpha subunit (UA), urease beta subunit (UB), the 66-kDa heat shock protein (HSP), and the 25-kDa protein (25K) were used as antigens for the ACELISAs. The antibody titers of the ACELISAs reflect the ratio of H. pylori-specific IgA to total IgA. The ratio is stable, although the antibody concentration fluctuates in gastric juice. By using ACELISAs it was possible to evaluate quantitatively not only serum IgA antibodies but also gastric juice secretory IgA (S-IgA) antibodies. In both serum IgA and gastric juice S-IgA ACELISAs, the titers of antibody to HSP and 25K were remarkably correlated with the histologic grade of gastritis, whereas those to UA and UB were not strongly correlated with histologic grade. Thus, it is useful for estimating the histologic grade of gastritis to quantify serum IgA and gastric juice S-IgA antibodies to HSP and 25K.     

A comparative immunohistochemical study of pancreatic islets in laboratory animals (rats, dogs, minipigs, nonhuman primates)

The aim of the present study was to distinguish and describe the patterns of distribution of pancreatic islets within the pancreas of four species of laboratory animals, including rats, dogs, minipigs and monkeys, and furthermore, to identify immunohistochemically various islet cell types and characterize their content. Histopathological examinations were performed on sections stained with hematoxylin and eosin (H&E) and immunostained using rabbit polyclonal antibodies (pAb) against insulin, glucagon, pancreatic polypeptide (PP), somatostatin, chromogranin A, keratin, bombesin and gastrin, or mouse monoclonal antibodies (mAb) against synaptophysin, Leu-7 and proliferating cell nuclear antigen (PCNA) in three-step rabbit immunoperoxidase (PAP) and streptavidin/peroxidase (StreptABC/HRP) reactions. Positive immunohistochemical reactions were observed in the pancreatic islets of all animal species with all antibodies, except with anti-bombesin and anti-gastrin antibodies. Our results revealed that: 1) there is species specific regional arrangement of islets in the pancreas, 2) each species presents a characteristic distribution of cells producing different hormones. 3) immunoreactivity with immunohistochemical markers varies between species and/or age. The present comparative immunohistochemical study could be helpful for answering questions which are important for understanding some of the intricate mechanisms that govern the integrated function of the endocrine pancreas.