Clinical and immunological implications of increase in CD208+ dendritic cells in tonsils of patients with immunoglobulin A nephropathy.

BACKGROUND: The therapeutic effect of tonsillectomy for immunoglobulin A nephropathy (IgAN) has been widely recognized, but the mechanism by which tonsillar immunity leads to glomerulonephritis has been unclear. We investigated subtypes and localization of dendritic cells (DCs) in tonsils and looked for relationships between the tonsillar DCs and the clinical features and renal histological changes of patients with IgAN. METHODS: We examined tonsils from 33 IgAN patients, using as control tonsillar specimens from subjects without glomerulonephritis. Five distinct markers of DCs (CD303, CD1c, CD209, CD208 and CD1a) were analyzed by immunohistochemistry and flow cytometry. The mRNA levels of these DC markers were evaluated using real-time polymerase chain reaction. The clinical data and histological results obtained evaluating renal biopsy tissues were statistically compared with immunological data. RESULTS: Of the five subtypes of DCs, CD208(+) DCs were significantly increased in the tonsils of IgAN patients compared with that of controls. Furthermore, the number of CD208(+) DCs in the tonsils was positively and linearly correlated with the proportion of crescentic glomeruli in renal biopsy tissues and with the urinary protein level. Only few CD208(+) cells, however, were found in the kidney biopsy specimens of IgAN patients. CONCLUSIONS: These observations suggest that increased CD208(+) DCs in tonsils may play a directive role in the pathogenesis of IgAN. The present results support the therapeutic significance of tonsillectomy for IgAN patients.

[Successful chemotherapy with a docetaxel regimen for primary signet-ring cell carcinoma of the urinary bladder-a case report].

Primary signet-ring cell carcinoma of the bladder is rare and has a poor prognosis. In addition, there are few successful chemotherapies for it. We report a case of chemotherapy with a docetaxel regimen which was efficacious in a 64-year-old Japanese man suffering from the disease. The onset of bilateral hydronephrosis led to the detection of his bladder tumor, and its pathological diagnosis was signet-ring cell carcinoma(immunohistochemistry showed cytokeratin 7+/20±). He was treated with chemotherapy rather than with surgery because the tumor invaded the abdominal wall and groin. To treat his disease, we performed 2 courses of a chemotherapy regimen comprised of S-1 and cisplatin, but it was not efficacious. We chose docetaxel as a second-line chemotherapy regimen,(60mg/m2, tri-weekly), and a clinical examination including contrast-enhanced CT showed that his disease had successfully responded to the chemotherapy.

Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours.

AIMS: Fibroblast activation protein (FAP)/seprase and dipeptidylpeptidase-IV (DPP-IV)/CD26 are serine integral membrane proteases. They are involved in tissue remodelling, cancer invasion and metastases, mechanisms that are controversial. The aim was to identify cell types that express FAP and DPP-IV in human bone and soft tissue tumours, and to determine whether there are any correlations between the expression of FAP and DPP-IV and the malignant potential of tumours. METHODS AND RESULTS: This study analysed in situ expression in 25 malignant and 13 benign human bone and soft tissue tumours. Reverse transcriptase-polymerase chain reaction analyses confirmed mRNA expression of FAP and DPP-IV in all individuals. Immunohistochemistry using pre-fixed frozen sections revealed that FAP was positive in low-grade myofibroblastic sarcoma, the fibroblastic component of osteosarcomas, and malignant fibrous histiocytomas, but negative in Ewing's sarcomas and rhabdomyosarcomas. DPP-IV showed similar immunohistochemical results. Among benign tumours, non-ossifying fibromas, desmoid tumours and chondroblastomas expressed both FAP and DPP-IV. Giant cells expressed DPP-IV in giant cell tumours. CONCLUSIONS: Our data suggest that FAP and DPP-IV are consistently expressed in bone and soft tissue tumour cells that are histogenetically related to activated fibroblasts and/or myofibroblasts, irrespective of their malignancy. DPP-IV is also expressed in monocyte-macrophage lineage cells.

Comparison of the effectiveness of geranylgeranylacetone with cimetidine in gastritis patients with dyspeptic symptoms and gastric lesions: a randomized, double-blind trial in Japan.

BACKGROUND AND AIM: Controversy remains regarding the treatment of choice for chronic gastritis patients with dyspeptic symptoms when Helicobacter pylori eradication is not indicated or fails for their gastric lesions. A multicenter, randomized, double-blind trial was performed to compare the effectiveness of geranylgeranylacetone (GGA), a mucoprotective drug, against cimetidine (CIT), an H(2)-receptor antagonist, on the treatment of erosions and petechial hemorrhage in H. pylori-infected patients with dyspeptic symptoms. METHODS: 128 H. pylori-positive gastritis patients with mucosal erosions and/or petechial hemorrhage were randomized to receive 150 mg GGA t.i.d. or 400 mg CIT b.i.d. for 2 weeks. Improvement and cure rates on endoscopic findings, symptom disappearance rates, and changes in mucosal neutrophil infiltration were compared. RESULTS: Endoscopic improvement rates were significantly higher in the GGA group (n = 50) than in the CIT group (n = 54; 86.0 vs. 64.8%, p = 0.014). Endoscopic cure rates were also significantly higher for GGA than for CIT (80.0 vs. 55.6%, p = 0.012). Symptom disappearance rates were 52.0% for GGA and 42.6% for CIT, but the difference was not significant. There was also no significant difference in mucosal neutrophil infiltration between the groups. CONCLUSION: GGA treatment appears to be more effective than CIT for chronic gastritis-associated erosion and petechial hemorrhage.

Up-regulation of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase were coupled with that of type I procollagen in granulation tissue response after the onset of aortic dissection.

The pathophysiological significance of matrix metalloproteinases (MMPs) in aortic dissection remains poorly understood. The purpose of the present study is to clarify the significance of MMPs in aortic dissection. The activities and distributions of MMP-2, membrane-type 1-MMP (MT1-MMP), and MMP-9 were evaluated by gelatin zymography, immunohistochemistry, and in situ hybridization in 29 patients and seven autopsy cases. To assess if these MMPs are related to a tissue remodeling process, we compared the expression of these MMPs with that of type I procollagen and platelet-derived growth factor receptor beta chain (PDGF Rbeta). Patients were divided into three groups based on histological findings: acute, intermediate, and healed groups. The most remarkable changes were observed in the intermediate group, in which MMP-2 activity peaked and tissue expression of mRNAs for MMP-2 and MT1-MMP were observed in spindle-shaped cells in the neointima, organizing thrombus, and the adventitia. These expression patterns were essentially coupled with those of type I procollagen mRNA and PDGF-Rbeta protein. The association of MMP-2, MT1-MMP, type I procollagen, and PDGF-Rbeta suggests that MMP-2 and MT1-MMP could be involved not only in the degradation of aortic tissue but also in tissue remodeling, which may be associated with the healing process.

Infiltration of CD19+ plasma cells with frequent labeling of Ki-67 in corticosteroid-resistant active ulcerative colitis.

Abnormalities in humoral immunity are implicated in the pathogenesis of ulcerative colitis. However, the detailed mechanisms of B-cell activation in the locale remain unaccounted for. We analyzed ulcerative colitis from the standpoint of lymphocytic expansion in the loco. Intestinal specimens obtained at surgery from 30 patients with ulcerative colitis treated with corticosteroids and 15 with Crohn's disease were analyzed by immunohistochemistry and flow cytometry. Ulcerative colitis was characterized by a diffuse distribution of Ki-67(+) small round cells particularly in the ulcer base (that were CD19(+) and CD20(-)), with a significant number of them also CD138(+). Immunoelectron microscopy for CD19 revealed an abundance of rough endoplasmic reticulum in the cytoplasm. These indicated that they are of immature plasma lineage cells. By contrast, plasma cells in Crohn's disease were negative for CD19, and the labeling for Ki-67 was infrequent, showing mature phenotype. Flow cytometry revealed an occurrence of CD19(+) and CD20(-) cells in ulcerative colitis but not in Crohn's disease. The labeling index of Ki-67 among CD19(+) plasma cells was positively correlated with the clinical activity of ulcerative colitis. High labeling of Ki-67 in CD19(+) plasma cells is specific for active ulcerative colitis that was resistant to medical treatment by corticosteroids.

Gastric epithelial cell turnover and mucosal protection in Japanese children with Helicobacter pylori infection.

BACKGROUND: In adults, epithelial cell proliferation and apoptosis of the gastric mucosa are induced by Helicobacter pylori infection and are associated with gastric atrophy or gastric carcinoma. In children, there are few studies about such epithelial changes. To elucidate the role of H. pylori infection in gastric mucosal inflammation, we immunohistochemically examined gastric mucosa of Japanese children. METHODS: Biopsy specimens obtained from the gastric antrum and corpus of H. pylori-infected (n = 13) and noninfected children (n = 15) were studied for immunolocalization of Ki-67, single-strand DNA, manganese superoxide dismutase (Mn-SOD), and CD68, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In 10 patients with successful eradication, pre- and posttreatment results were compared. RESULTS: In both gastric antrum and corpus, neutrophil and mononuclear cell infiltration, epithelial cell proliferation, and apoptosis significantly increased in H. pylori-infected patients, predominantly in the antrum. In the antrum of H. pylori-infected patients, there was positive correlation between the degrees of neutrophil infiltration and cell proliferation (P < 0.05) or apoptosis (P < 0.05). H. pylori eradication improved mucosal inflammation, cell proliferation (P < 0.001), and apoptosis (P < 0.01) in the antrum. Mn-SOD immunoreactivity and CD68-positive macrophages in the antrum, which significantly increased in H. pylori-infected patients, decreased after the eradication. CONCLUSIONS: H. pylori infection induced gastric mucosal inflammation and epithelial cell turnover in children. Moreover, gastric mucosal defense mechanism against H. pylori infection was activated. H. pylori eradication in childhood might prevent the accumulation of gastric epithelial cell damage.

Accumulation of phosphorylated alpha-synuclein in aging human brain.

Alpha-synuclein in Lewy bodies (LBs) is phosphorylated at Ser129. We raised monoclonal and polyclonal antibodies to this phosphorylation site (psyn) and examined 157 serial autopsy brains from a geriatric hospital. Anti-psyn immunoreactivity was observed in 40 of these cases (25.5%). Immunohistochemistry revealed 4 novel types of pathology: diffuse neuronal cytoplasmic staining (pre-LB); neuropil thread-like structures (Lewy threads); dot-like structures similar to argyrophilic grains (Lewy dots); and axons in the white matter (Lewy axons). This novel pathology was abundantly present around LBs and also involved the limbic subcortical white matter, the cerebral cortical molecular layer, and the spongiform changes of the medial temporal lobe associated with cases of dementia with LBs (DLB). The phosphorylated alpha-synuclein was limited to the temporal lobe in cases of Parkinson disease, spread from the temporal lobe to the frontal lobe in cases of DLB transitional form and further spread to the parietal and occipital lobes in DLB neocortical form. Our findings suggest that LB-related pathology initially involves the neuronal perikarya, dendrites, and axons, causes impairment of axonal transport and synaptic transmission, and later leads to the formation of LBs, a hallmark of functional disturbance long before neuronal cell death.

Comparison of the distribution and numbers of antigen-presenting cells among T-lymphocyte-mediated dermatoses: CD1a+, factor XIIIa+, and CD68+ cells in eczematous dermatitis, psoriasis, lichen planus and graft-versus-host disease.

Antigen-presenting cells (APCs) participate in the initiation of the inflammatory process in various immune-mediated dermatoses through the activation of antigen-specific T lymphocytes. The skin contains several different subsets of APCs. To investigate the role of these APCs in T-cell immune-mediated inflammation, we examined the distribution and numbers of epidermal and dermal CD1a(+) dendritic cells (DCs), factor XIIIa(+) dermal DCs, and CD68(+) macrophages in five T-cell-mediated inflammatory skin diseases. Immunohistochemistry of CD1a, factor XIIIa, and CD68 was performed using paraffin-embedded tissue obtained from a total of 51 patients with eczematous dermatitis (histologically spongiotic dermatitis), psoriasis, lichen planus, acute graft-versus-host disease (GVHD), and chronic GVHD. The numbers of positive cells for each staining were compared with those in site-matched normal skin control specimens from aged-matched subjects. In spongiotic dermatitis and lichen planus, the numbers of epidermal and dermal CD1a(+) cells and factor XIIIa(+) cells were significantly greater than in normal control skin, while in psoriasis only factor XIIIa(+) cells were significantly increased in number. Acute and chronic GVHD showed a reduced number of dermal CD1a(+) cells. Interestingly, factor XIIIa(+) cells were decreased in acute GVHD while they were increased in chronic GVHD. There was a significant reduction in epidermal CD1a(+) cells in acute GVHD, but not in chronic GVHD. The differences in the numbers of APCs in lesional skin appeared to reflect differences in the pathophysiology of these inflammatory skin diseases.

Expression of mucosal addressin cell adhesion molecule 1 on vascular endothelium of gastric mucosa in patients with nodular gastritis.

AIM: The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin alpha4beta7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT). Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center, strongly associated with H pylori infection. The purpose of this study was to address the implication of the MAdCAM-1/integrin beta7 pathway in NG. METHODS: We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls. A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM-1 and integrin beta7. In simultaneous viewing of serial sections, the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated. We also performed immunostaining with anti-CD20, CD4, CD8 and CD68 antibodies to determine the lymphocyte subsets co-expressing integrin beta7. RESULTS: Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection. Of note, the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls. Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates. Integrin beta7-expressing mononuclear cells, mainly composed of CD20 and CD4 lymphocytes, were associated with vessels lined with MAdCAM-1-expressing endothelium. CONCLUSION: Our results suggest that the MAdCAM-1/integrin alpha4beta7 homing system may participate in gastric inflammation in response to H pylori-infection and contributes to MALT formation, typically leading to the development of NG.

[Marked decrease of intracranial atherosclerosis in contrast with unchanged coronary artery stenosis in Japan].

We conducted comparative studies on intracranial atherosclerosis and coronary artery stenosis over the past 28 years. Two-year consecutive autopsy case studies from an urban geriatric hospital between 1974-1975 (Group I. 484 cases). 1986-1987 (Group II, 504 cases) and 2000-2001 (Group III, 273 cases) were employed. Atherosclerotic changes of the bilateral middle cerebral arteries and basilar artery were semiquantitatively evaluated as none (0), mild (1), moderate (2) and severe (3) and values of the 3 arteries were totalled to give a value of 0-9 which was taken as the intracranial atherosclerotic index (ICAI). The coronary stenotic index was calculated as previously reported (Sugiura et al 1969). ICAI and CSI were directly compared with each other, together with risk factors for each, including mean blood pressure (BP), serum level of total cholesterol (Tch) and the history of diabetes mellitus (DM+). Chronologically ICAI decreased dramatically but CSI did not change at all. There was continuous lowering of BP, elevation of Tch and increased incidence of DM+. There was a significant positive correlation in BP in relation to both ICAI and CSI (p < 0.01). DM+ vs. CSI (p < 0.01) and ICAI (p < 0.05), and Tch vs. CSI (p < 0.01) but not ICAI. Regression analysis highlighted age and BP as major risk factors for ICAI. Our study provides the first morphological confirmation of marked decrease of the intracranial atherosclerosis in the recent 28 years, in contrast with unchanged coronary stenosis in Japanese elderly subjects.

Accumulation of CCR5+ T cells around RANTES+ granulomas in Crohn's disease: a pivotal site of Th1-shifted immune response?

Immunological abnormalities are implicated in the pathogenesis of inflammatory bowel disease (IBD), that is, Crohn's disease and ulcerative colitis. In particular, Crohn's disease is considered to be a T helper type 1 (Th1)-shifted disease. Chemokines and their receptors are involved in various immune responses including Th1- and Th2 responses. In this study, we analyzed chemokines and their receptors by immunohistochemistry, using frozen sections derived from 33 patients with Crohn's disease and 24 with ulcerative colitis. In inflamed mucosa, small mononuclear cells predominantly expressed CCR5 and CXCR3, the receptors selectively expressed on Th1 cells, without significant differences between Crohn's disease and ulcerative colitis. We then focused on the noncaseating granulomas that are characteristic of Crohn's disease. Granuloma cells, observed in all the layers of intestinal tissues, were positive for RANTES/CCL5 protein along their cell membranes. Lymphocytes surrounding granulomas were mostly CCR5+ and CXCR3+ T cells with CD4+ and CD8+ cells at similar frequencies. Granuloma cells were positive for RANTES mRNA by in situ hybridization. By contrast, lymphoid aggregates in Crohn's disease and lymphoid follicles in the normal intestinal mucosa were characterized by abundant B cells, a predominance of CD4+ T cells over CD8+ T cells, and low frequencies of cells expressing CCR5 or CXCR3. Together with the notion that granuloma cells are possible antigen-presenting cells, our results suggest that the noncaseating granulomas could be one of the crucial sites of Th1-shifted immune responses in Crohn's disease.

Constant and severe involvement of Betz cells in corticobasal degeneration is not consistent with pyramidal signs: a clinicopathological study of ten autopsy cases.

This report concerns a clinicopathological study of three additional patients with corticobasal degeneration (CBD), described here for the first time, and a clinicopathological correlation between pyramidal signs and upper motor neuron involvement, in ten autopsy cases of CBD, including seven cases reported by us previously. We investigated pyramidal signs, including hyperreflexia, Babinski sign, and spasticity, and involvement of the primary motor cortex and pyramidal tract, focusing on the astrocytosis of the fifth layer of the primary motor cortex. Pyramidal signs were observed in six (60%) of the ten cases. Hyperreflexia was evident in six patients (60%), with spasticity being observed in three patients (30%). Loss of Betz cells associated with prominent astrocytosis and presence of ballooned neurons in the fifth layer of the primary motor cortex was observed in all ten cases. In all cases, involvement of the pyramidal tract was obvious in the medulla oblongata, without involvement of the pyramidal tract in the midbrain. Constant and severe involvement of the fifth layer of the primary motor cortex, including the Betz cells, has not previously been reported in CBD. We suggest that the pyramidal signs in CBD have been disregarded.

Selective infiltration of CCR5(+)CXCR3(+) T lymphocytes in human colorectal carcinoma.

T cell infiltration in colorectal cancer is associated with a favorable prognosis, suggesting an occurrence of a certain degree of anti-tumor immunity. T helper type 1 (Th1) and Th2 cells are now known to selectively express CC-chemokine receptor 5 (CCR5)/CXC-chemokine receptor 3 (CXCR3) and CCR4, respectively. To clarify the mechanism of T cell infiltration, we examined in situ expression of these chemokine receptors and their respective chemokine ligands in 40 cases of human colorectal cancer. Immunohistochemistry showed a predominant accumulation of T cells expressing CCR5 and CXCR3 mainly along the invasive margin, whereas those expressing CCR4 were rare. Flow cytometric analysis showed that more than half of CD8(+) T cells and a fraction of CD4(+) cells isolated from fresh tumor tissues co-expressed CCR5 and CXCR3, and CD8(+) T cells and CD4(+) cells predominantly produced interferon-gamma (IFN-gamma) over interleukin-4 (IL-4) after in vitro stimulation. RANTES/CCL5, a ligand of CCR5, was localized within infiltrating CD8(+) T cells in a granular pattern, whereas IP-10/CXCL10, a ligand of CXCR3, was localized in cancer cells and macrophages along the invasive margin. These data were consistent with an active recruitment of T cells expressing CCR5 or CXCR3 into the invasive margin of colorectal cancer. With the previous clinicopathological studies showing a favorable prognostic impact of T cell infiltration in colorectal cancer, our study supports the occurrence of a certain level of Th1-shifted cellular immune responses in human colorectal cancer.

Tissue Localization of Nerve Growth Factor Receptors: trk A and Low-Affinity Nerve Growth Factor Receptor in Neuroblastoma, Pheochromocytoma, and Retinoblastoma.

The immunohistochemical localization of nerve growth factor receptor (NGFR)-high-affinity NGFR (trk A) and low-affinity NGFR (LNGFR)-was investigated in 23 neuroblastoma group tumors, 18 pheochromocytomas, 2 mixed neuroendocrine-neural tumors, and 16 retinoblastomas. trk A was expressed in the tumor cells of all neuroblastomas, pheochromocytomas, and retinoblastomas. Immunoreactive intensity was especially strong in the larger ganglionic tumor cells of ganglioneuroblastoma and ganglioneuroma. Messenger RNA (mRNA) of trk A was also strongly expressed in the ganglionic cells of ganglioneuroblastomas and chromaffin cells of pheochromocytomas by in situ hybridization method. LNGFR was negative in the tumor cells of neuroblastoma; however, it showed strong immunoreactivity in ganglionic tumor cells and Schwann cells of ganglioneuroblastoma/ganglioneuroma, and sustentacular cells of pheochromocytoma. Although normal retina expressed both trk A and LNG FR, tumor cells of retinoblastoma were positive for only trk A but negative for LNGFR. Such differences in the expression of trk A and LNGFR may reflect neuronglial interactions in the survival and maturation of the sympathetic nerves, retina, and tumors in these tissues.

Immunohistochemistry of Gastric Carcinomas and Associated Diseases: Novel Distribution of Carcinoembryonic Antigen and Secretory Component on the Surface of Gastric Cancer Cells 1.

Carcinoembryonic antigen (CEA) and secretory component (SC) were localized by peroxidase-labeled antibody immunocytochemistry in normal and abnormal human gastric mucosa. In normal epithelium, both glycoproteins were absent or only faintly present, but in intestinal metaplasia and carcinoma both were prominently present. CEA and SC on the surfaces of metaplastic epithelial cells were polarized. That is, CEA was expressed only on the microvillous surface and SC was expressed only on the basolateral surface. In gastric cancer, CEA and SC were distributed over the entire surface of the neoplastic cells. Thus, deviations from the normal differentiation and maturation of gastric epithelial cells were accompanied by abnormalities in surface expression of CEA and SC. These observations, together with compatible observations previously made in colonic neoplasia (DJ Ahnen, PK Nakane, and WR Brown, Cancer 49:2077, 1982), suggest that loss of polarity of surface membrane components is a characteristic of neoplastic epithelial cells.

Immunolocalization of 3ß-hydroxysteroid dehydrogenase in human adrenal cortex and in its disorders.

Immunohistochemical localization of 3ß-hydroxysteroid dehydrogenase/Δ5→4-isomerase (3ß-HSD), which converts Δ5-3ß-hydroxysteroids to Δ4-3-ketosteroids, was performed in the human adrenal gland and in its disorders by employing a specific antibody raised against the enzyme purified from human placenta. Immunoreactivity of 3ß-HSD was present in all three cortical zones of the adrenal glands obtained at autopsy, while in surgically removed adrenal glands, immunoreactivity was dominant in the zona fasciculata (ZF), with faint immunoreactivity in the zona glomerulosa (ZG) and the zona reticularis (ZR). Intracortical localization of 3ß-HSD in the adrenal glands obtained at autopsy may represent an adrenal adaptation to antemortem stress, with shifting of adrenal pregnenolone- a substrate of 3ß-HSD - as well as steroid 17α-hydroxylase from adrenal androgen synthesis to glucocorticoid synthesis. In adrenocortical hyperplasia, marked immunoreactivity was observed in the ZG and outer ZF in adrenal glands with idiopathic hyperaldosteronism and in the ZF and ZR, especially in cortical micronodules, in the adrenal glands associated with Cushing's disease. In aldosteronoma and Cushing's adenoma, immunoreactivity of the enzyme was much more intense in large clear tumor cells than in small compact tumor cells. Immunolocalization of 3ß-HSD can yield important information toward an understanding of adrenal steroid metabolism in both physiological and pathological processes.

Immunohistochemical Localization of Chromostatin and Pancreastatin, Chromogranin A-Derived Bioactive Peptides, in Normal and Neoplastic Neuroendocrine Tissues.

Despite the widespread distribution of chromogranin A (CgA) in neuroendocrine tissues, the biological function of CgA has not yet been elucidated. The primary amino acid sequence of CgA, elucidated by cDNA analysis, has been revealed to include several pairs of basic amino acid residues that are homologous to the bioactive peptides, such as pancreastatin (PST) and chromostatin (CST). Using antibodies for human PST and CST, the immunohistochemical localization of these peptides was investigated in neuroendocrine tissues, including human pituitary glands, pancreas, adrenal medulla, various types of neuroendocrine neoplasms (13 pheochromocytomas, 10 medullary thyroid carcinomas, 11 pancreatic endocrine tumors, and 19 carcinoid tumors), and the cell line QGP-1N derived from human somatostatin-producing pancreatic endocrine tumor. Variable immunoreactive intensities of PST and CST were seen, but both peptides were detectable in all neuroendocrine tissues and in most of the neoplasms. Immunoreactivity for both PST and CST was observed in 100 and 73%, respectively, of pancreatic endocrine tumors, all pheochromocytomas, and 80 and 40%, respectively, of medullary thyroid carcinomas, as well as all nonrectal carcinoid tumors. In rectal carcinoids, cells immunoreactive for PST and CST were sparse. The distribution of PST and CST was similar to that of CgA, and it is considered that these peptides are simultaneously processed from CgA, and may play roles in autocrine and paracrine regulation on various hormones in addition to their previously known functions.

Localization of antigen-presenting cells in Helicobacter pylori-infected gastric mucosa.

Helicobacter pylori (HP) infection is known to induce the specific immune response in the gastric mucosa. The immune response is triggered by presentation of antigen peptides on the major histocompatibility assembly of the antigen-presenting cells (APC) with the assistance of costimulatory molecules such as B7-1 (CD80) and B7-2 (CD86). Their counter-receptors or ligands on T cells are CD28 or cytotoxic lymphocyte-associated molecule-4. The aim of the present study was to clarify the localization of APC and their relation with T cells in HP-infected human gastric mucosa. Our findings suggest that the macrophages in the lamina propria may mainly act as APC in the HP-infected gastric mucosa, and the triggered immune response might be involved in the mucosal immune response in the inflamed gastric mucosa to invasive antigens related to HP organisms.