Biomedical subjects

M Hayama

Publications and source records attributed to M Hayama.

At least 19 recordsLinked to original sources

PubMed2003

Primary gastric T-cell lymphoma not associated with human T-lymphotropic virus type I: a case report and review of the literature.

Primary gastric T-cell lymphoma (PGTL) not associated with human T-lymphotropic virus type I (HTLV-I) is extremely rare and such a case is reported herein. The patient was a 58-year-old Japanese male presenting with submucosal tumor of the stomach identified on endoscopic examination. The lesion was diagnosed as non-Hodgkin's lymphoma by endoscopic biopsy and classified as peripheral T-cell lymphoma, unspecified, due to clonal rearrangement of the T-cell receptor beta (TCR) gene and expression of TCR beta protein in the absence of B-cell genotypes and phenotypes. Unlike previously reported cases of HTLV-I-unassociated PGTL, lymphoma in the current case was characterized histologically as "low grade" and phenotypically as CD4+, TIA-1+, granzyme B+, and CD103-. The lymphoma responded well to chemotherapy and radiation, and the patient was well with no detectable disease 10 months after initiation of therapy. A review of patients with PGTL in the literature revealed a few long-term survivors, and the investigation of therapeutic strategies for PGTL is, therefore, necessary.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Duodenogastric reflux and Helicobacter pylori infection synergistically increase gastric mucosal cell proliferative activity in Mongolian gerbils.

BACKGROUND: Helicobacter pylori and duodenogastric reflux (DGR) are both recognized as aetiological factors in chronic gastritis and gastric carcinogenesis. In this study, a Mongolian gerbil (MG) model was used to investigate the histopathological changes in the gastric mucosa resulting from DGR and/or H. pylori infection. METHODS: One-hundred-and-eleven 7-week-old, specific-pathogen-free, male MGs were divided into four groups: normal controls, gerbils with surgically induced DGR, and H. pylori-infected gerbils with and without DGR. Gerbils were killed 4, 12 and 26 weeks after DGR surgery, their stomachs removed and sections prepared. Sections were fixed immediately in 20% phosphate-buffered formalin and subjected to haematoxylin and eosin staining, Alcian blue at pH 2.5/periodic acid-Schiff staining, and immunostaining for smooth muscle cells, H. pylori and 5'-bromo-2'-deoxyuridine (BrdU). RESULTS: The gastric mucosa of H. pylori-infected gerbils showed chronic active gastritis irrespective of DGR throughout the experimental period. The gastric mucosa of H. pylori-infected gerbils with DGR demonstrated higher BrdU labelling than in the other groups. CONCLUSIONS: In MGs, DGR and H. pylori infection synergistically increased gastric mucosal cell proliferative activity. DGR and H. pylori infection may be involved synergistically in gastric carcinogenesis by increasing cell proliferative activity.

Animals↗

PubMed2001

Ceramide accelerates dephosphorylation of extracellular signal-regulated kinase 1/2 to decrease prostaglandin D(2) production in RBL-2H3 cells.

In the present study, the effect of ceramide on antigen-stimulated phosphorylation of extracellular signal-regulated kinase (ERK) in the mechanism responsible for regulating production of prostaglandin (PG) D(2) was investigated in the mast cell line, RBL-2H3 cells. Cell-permeable C(6)-ceramide (N-hexanoylsphingosine) suppressed antigen-stimulated phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase. Ceramide also inhibited production of PGD(2) and an increase in the activity of cytosolic phospholipase A(2) (cPLA(2)), whereas it did not influence the tyrosine phosphorylation of major cellular proteins in response to antigen. The ceramide-induced inhibition of ERK1/2 phosphorylation and of cPLA(2) activation was suppressed by orthovanadate, a tyrosine phosphatase inhibitor, but not by okadaic acid, a serine/threonine phosphatase inhibitor. Addition of ceramide to the lysate prepared from antigen-stimulated cells reduced the phosphorylated ERK1/2, and orthovanadate effectively prevented the reduction. These results suggest that ceramide accelerates the dephosphorylation of phosphorylated ERK1/2 via activation of a protein tyrosine phosphatase, thus preventing activation of cPLA(2) and production of PGD(2).

Animals↗

PubMed2001

Secretory phospholipase A2 mediates cooperative prostaglandin generation by growth factor and cytokine independently of preceding cytosolic phospholipase A2 expression in rat gastric epithelial cells.

Transforming growth factor (TGF)-alpha and interleukin (IL)-1beta are responsible for the healing of gastric lesions through, in part, prostaglandin (PG) generation. We examined the contribution of cytosolic and secretory phospholipase A(2)s (cPLA(2) and sPLA(2)) to the PG generation by rat gastric epithelial cells in response to both stimuli. Stimulation with TGF-alpha for 24 h increased cPLA(2) and cyclooxygenase (COX)-2 markedly, PGE(2) slightly, and type IIA sPLA(2) and COX-1 not at all, whereas IL-1beta increased sPLA(2) only. Both stimuli synergistically increased PGE(2), sPLA(2), and the two COXs but not cPLA(2). The onset of the PGE(2) generation paralleled the sPLA(2) release but was apparently preceded by increases in cPLA(2) and the two COXs. The increase in PGE(2) was impaired by inhibitors for sPLA(2) and COX-2 but not COX-1. cPLA(2) inhibitors suppressed PGE(2) generation by TGF-alpha alone but not augmentation of PGE(2) generation or sPLA(2) release by IL-1beta in combination with TGF-alpha. Furthermore, despite an increase in cPLA(2) including its phosphorylated form (phosphoserine), -induced arachidonic acid liberation was impaired in the TGF-alpha/IL-1beta-stimulated cells, in which p11, a putative cPLA(2) inhibitory molecule, was also increased and co-immunoprecipitated with cPLA(2). These results suggest that synergistic stimulation of sPLA(2) and COX-2 expression by TGF-alpha and IL-1beta results in an increase in PGE(2). Presumably, the preceding cPLA(2) expression is not involved in the PGE(2) generation, because of impairment of its hydrolytic activity in the stimulated cells.

Animals↗

PubMed2001

Adenocarcinoma of female paraurethral duct showing neuroendocrine differentiation.

Two cases are presented in which a female urethral adenocarcinoma took the form of a diverticular cancer. The pathologic examination of each tumor revealed a columnar/mucinous type of adenocarcinoma with evidence of abundant mucous secretion. Some of the cancer cells were positive on immunohistochemical staining with the conventional neuroendocrine marker chromogranin A, indicating focal neuroendocrine differentiation. The present cases may indicate a possible site of origin for female paraurethral adenocarcinomas.

Adenocarcinoma, Mucinous↗

PubMed2001

Experimental study of oversized grafts in a canine living-donor lobar lung transplantation model.

BACKGROUND: For infants and small children, organ transplantation is limited by the size discrepancy between donor and recipient. To address this problem, the use of over-sized grafts from living-relative donors could potentially expand the donor pool. The aim of this experimental study was to evaluate the effect of oversized grafts on early pulmonary function and to identify an indicator for acceptable size discrepancy. METHODS: Fourteen bilateral lobar lung allotransplant operations were performed without cardiopulmonary bypass in weight mismatched pairs of dogs. Animals were divided into 2 groups: Group I (n = 7), donor/recipient lung volume ratio < 2.85; Group II (n = 7), donor/recipient lung volume ratio >2.85. Pulmonary function of the recipient was measured before chest closure, after chest closure, and after the ventilator was removed. RESULTS: Pulmonary vascular resistance and airway pressure significantly increased in Group II after chest closure (1493 +/- 195 dynes sec cm(-5) and 14.4 +/- 0.9 mm Hg vs 2784 +/- 140 dynes sec cm(-5) and 23.4 +/- 1.2 mm Hg, p < 0.001). After the ventilator was removed, all recipients in Group I showed PaO2 > 239 mm Hg and PaCO2 < 76 mm Hg, whereas, all recipients in Group II showed PaO2 < 116 mm Hg and PaCO2 > 169 mm Hg. The donor/recipient chest circumference ratio was less than 1.3 in all but 1 dog in Group I. CONCLUSIONS: Acceptable, oversized grafts provide adequate pulmonary function, although excessively oversized grafts cause significant impairment in pulmonary function after chest closure. Chest circumference provides useful size-match criteria when oversized grafts are used in this canine experimental model.

Animals↗

PubMed2001

Histone H3 mRNA in situ hybridization for identifying proliferating cells in human pancreas, with special reference to the ductal system.

In general, the incidence of proliferating cells parallels that of carcinogenesis. We have investigated proliferating activity and phenotype expression in epithelial cells in normal tissue, mucinous metaplasia and ductal adenocarcinoma of the pancreas. Twenty-eight resected pancreases (15 cases of pancreatic ductal adenocarcinoma and 13 cases of other diseases) were examined. Formalin-fixed, paraffin-embedded tissue sections were examined for proliferating cell activity using histone H3 mRNA in situ hybridization and immunostaining for Ki-67. In the normal pancreas, the labelling indices for proliferating cells were low and no generating zone was found. The following progressive increase was found in the labelling indices: normal ductal epithelium < mucinous metaplasia without papillary hyperplasia < mucinous metaplasia with papillary hyperplasia < ductal carcinoma. In the pancreatic ductal adenocarcinomas, the S-phase fraction, as defined by the ratio H3-mRNA-labelling index/Ki-67-labelling index, increased as the degree of differentiation decreased. Mucinous metaplasia with papillary hyperplasia showed organoid differentiation toward pyloric mucosa. If used in combination with other proliferative markers on paraffin-embedded tissue sections, histone H3 mRNA in situ hybridization could open broader perspectives on the biology of cell proliferation in the pancreatic ductal system.

Adenocarcinoma↗

PubMed2001

Prostatic adenocarcinoma with marked neuroendocrine differentiation.

A case is presented of prostatic cancer with marked neuroendocrine differentiation. Double-labeled immunohistochemical staining was performed with prostate-specific antigen and Chromogranin A. Both antibodies were localized to some of the cancer cells with Paneth cell-like features. Furthermore, most of the cancer cells were positively stained with luminal cell marker CAM 5.2, suggesting that neuroendocrine cells originated from the prostatic luminal cells.

Adenocarcinoma↗

PubMed2001

Proliferation of alpha-smooth muscle actin-containing stromal cells (myofibroblasts) in the lamina propria subjacent to intraepithelial carcinoma of the esophagus.

BACKGROUND: The lamina propria of the digestive tract is the space containing vessels, myofibroblasts, and other interstitial components. The present study was undertaken to elucidate the relationships between the proliferation of myofibroblasts within this space and other histological features such as inflammatory cell infiltration and proliferation of blood vessels. METHODS: Thirty-eight cases in total-comprising 19 cases of early and 19 cases of advanced esophageal squamous cell carcinoma with intraepithelial extension (the former including 10 lesions of carcinoma in situ and 15 lesions of carcinoma with invasion only into the lamina propria)-were examined using H&E staining, Azan Mallory staining, and immunostaining for the characterization of mesenchymal cells in the lamina propria against alpha-smooth muscle actin (alphaSMA), desmin, vimentin, factor VIII, collagen type IV, laminin, or inflammatory cells (L26, UCHL1, Kp1, and c-kit). The proliferative potential of myofibroblasts was evaluated by measuring the total length of the bundles of myofibroblasts per case. RESULTS: Proliferation of alphaSMA-containing stromal cells: i) occurred in the lamina propria subjacent either to intraepithelial carcinomas (64%) or to the intraepithelial extension of carcinoma tissue (47%), and ii) showed a significant correlation with both the degree of mononuclear cell infiltration (mostly UCHL1-positive T cells) and the total length of the carcinoma tissue in each case. CONCLUSIONS: Proliferation of alphaSMA-containing stromal cells in the lamina propria may be involved in altering the endoscopic features of the esophagus in cases with intraepithelial carcinoma or an intraepithelial extension of carcinoma tissue.

Actins↗

PubMed2001

Helicobacter pylori and two ultrastructurally distinct layers of gastric mucous cell mucins in the surface mucous gel layer.

BACKGROUND AND AIMS: Helicobacter pylori locate not only on the apical surface of surface mucous cells but also in the mucous gel layer covering the gastric mucosa. The present study was undertaken to observe the mucous gel layer itself and any H pylori in this layer at the electron microscopic level, and to determine whether H pylori proliferate in this layer. METHODS: We examined resected human stomachs (five cases, fixed in Carnoy's solution, paraffin embedded) under the light microscope, and gastric biopsy specimens (10 cases, fixed in glutaraldehyde with or without osmium, epoxy embedded) under the electron microscope. We performed histochemical staining for gastric mucins and immunostaining for H pylori, gastric gland mucous type mucins, and intestinal mucins. RESULTS: Under the electron microscope, surface mucous cell type mucins and gland mucous cell type mucins in the mucous gel layer covering gastric mucosa without intestinal metaplasia showed reticular and band like structures, respectively. H pylori were frequently found as small aggregates within the mucous gel layer of surface mucous cell type mucins, and H pylori within these aggregates were seen dividing. H pylori were frequently found in the mucous gel layer of the surface mucous cell type mucins along the border with the layer of gland mucous cell mucins. Occasionally, H pylori were trapped by frayed thin threads of the gland mucous cell type mucins. CONCLUSIONS: The two types of gastric mucins in the mucous gel layer differ in ultrastructure. H pylori preferentially colonise and form microcolonies within the mucous gel layer of surface mucous cell type mucins. Mucins from gland mucous cells may disturb the movement of H pylori within the mucous gel layer.

Adult↗

PubMed2001

Cell lineage specificity of newly raised monoclonal antibodies against gastric mucins in normal, metaplastic, and neoplastic human tissues and their application to pathology diagnosis.

The specificity of monoclonal antibodies against gastric mucins (designated as HIK1083, PGM 36, and PGM 37) was studied immunohistochemically in normal, metaplastic, and neoplastic human tissues. These antibodies labeled class III mucin-producing cells identified by paradoxical concanavalin A staining in normal stomach, duodenum (Brunner gland), biliary tract, and main pancreatic duct; in mucinous metaplasia of pancreas and gallbladder; and in adenocarcinomas of stomach (90%), bile duct (80%), gallbladder (100%), pancreas (80%), lung (100% of goblet cell type adenocarcinomas), ovary (67% of mucinous carcinomas), and uterine cervix (100% of adenoma malignum tumors). Normal and neoplastic cells of esophagus, colon, salivary gland, kidney, endometrium, breast, prostate, and liver, as well as normal small intestine, lung, and uterine cervix, were all negative. The antibodies used should be valuable for the detection of class III mucin and class III mucin-producing cells in normal, metaplastic, and neoplastic tissues.

Antibodies, Monoclonal↗

PubMed2001

[Role of ultrasonography in diagnosis of neutropenic enteritis: a study of 4 cases].

Neutropenic enteritis is a septic or inflammatory disease of the colon. It is usually encountered in patients with hematological malignancy who have undergone chemotherapy, and it presents as fever, diarrhea, and abdominal pain, although the symptoms are not always specific. The diagnostic features of neutropenic enteritis revealed by barium enema, CT and ultrasonography have been reported previously. Here we report 4 cases of neutropenic enteritis in which ultrasound was used for diagnosis, and also for monitoring the clinical course of the disease. Because neutropenic enteritis is rapidly progressive, early diagnosis and therapeutic intervention are required. We believe that ultrasonography is a useful method for examining patients with neutropenic enteritis, being noninvasive, mobile, and providing rapid results in real time, thus aiding early diagnosis and clinical follow-up.

Adult↗

PubMed2001

[Primary lymphoma of the vagina].

Primary vaginal non-Hodgkin's lymphomas (NHL) are rare, and are clinically difficult to differentiate from inflammatory diseases or vaginal cancer. Here, we present such a case in a 74-year-old woman complaining of fever and difficulty with urination. Pelvic examination revealed a tumor involving most of the vaginal wall, and pelvic MRI demonstrated vaginal wall thickening. A biopsy of this lesion confirmed NHL (diffuse large B-cell lymphoma), and the patient was admitted. Abdominal CT and MRI detected a vaginal tumor, and Ga scintigraphy confirmed accumulation in the pelvis, but no abnormalities were seen in other areas. Therefore, the patient was diagnosed as having NHL at clinical stage IB with low-intermediate risk (international prognosis index) (LDH 1,309 IU/L). The patient underwent three courses of CHOP therapy followed by radiotherapy, and complete remission was achieved. Primary vaginal NHL often affects women younger than 50 years of age, and abnormal hemorrhage is the initial symptom in many cases. There have been a number of reports of long-term survival following appropriate early chemotherapy and radiation therapy, suggesting that early diagnosis and treatment based on vaginal biopsy findings greatly influence the prognosis.

Aged↗

PubMed2000

Acceleration by ceramide of calcium-dependent translocation of phospholipase A2 from cytosol to membranes in platelets.

The effect of ceramide on Ca2+-dependent translocation of cytosolic phospholipase A2 (cPLA2) to membranes was studied. Pretreatment of platelets with sphingomyelinase or C6-ceramide (N-hexanoylsphingosine) led to apparent enhancement of Ca2+-ionophore A23187-stimulated arachidonic acid release but did not affect the cytosolic phospholipase A2 (cPLA2) activity. Under these conditions, the cPLA2 proteins in membranes increased significantly, compared with those by A23187 alone. Sphingomyelinase and C6-ceramide, but not C6-dihydroceramide, a control analog of C6-ceramide, also facilitated the Ca2+-dependent increase in the cPLA2 protein, as well as the activity, in membranes induced by addition of Ca2+ into platelet lysate. Protein kinase Calpha, which possesses a Ca2+-dependent lipid binding domain, was increased in membranes in a Ca2+-dependent manner, but the increase was not accelerated by sphingomyelinase or C6-ceramide. These findings suggest that ceramide in membranes potentiates Ca2+-dependent cPLA2 translocation from cytosol to membranes, probably through modification of membrane phospholipid organization.

Animals↗

PubMed2000

Inhibitory effect of cepharanthine on fibronectin production in growth factor-stimulated rat mesangial cells.

We examined the effect of cepharanthine, a biscoclaurine alkaloid, on extracellular matrix production in rat mesangial cells in response to platelet-derived growth factor (PDGF) or transforming growth factor-beta (TGF-beta). Stimulation of the cells with PDGF increased the amounts of fibronectin, one of extracellular matrix components. Pretreatment with cepharanthine (0.1-2 microM) suppressed the PDGF-stimulated increase in fibronectin in a dose-dependent manner. At a concentration of 2 microM, the alkaloid almost completely suppressed the production. Under the conditions, the alkaloid inhibited tyrosine phosphorylation of several proteins including PDGF beta receptor in PDGF-stimulated cells, and also tyrosine kinase activity of the receptor prestimulated with PDGF in a cell-free assay system. Furthermore, cepharanthine suppressed TGF-beta-stimulated fibronectin production at the same concentration ranges. Our results suggest that cepharanthine inhibits fibronectin production induced by growth factors, probably through suppression of receptor autophosphorylation.

Alkaloids↗

PubMed2000

Type II pneumocytes are preferentially located along thick elastic fibers forming the framework of human alveoli.

Type II pneumocytes were found to be preferentially located on thick elastic fibers which formed the main structural framework of the alveoli in humans. Eight lobes resected from eight patients with adenocarcinoma or atypical adenomatous hyperplasia and two lobes from two necropsies were examined. Four small specimens of normal lung tissue were obtained from each lobe fixed in a buffered formalin. Thick sections (200-300 microm) were stained with hematoxylin to contrast nuclei or with elastica staining to demonstrate elastic fibers and immunostained with an antibody against Thomsen-Friedenreich antigen after pretreatment with sialidase to visualize type II pneumocytes. Alveolar structure and the distribution of type II pneumocytes were examined in 3D reconstructions generated using a standard microscope, a personal computer and NIH-Image software. Nuclei including those of type I and type II pneumocytes and endothelial cells were distributed diffusely throughout the alveolar wall. Thick elastic fibers constructed the main structural framework of the alveoli and formed the sides of the polygonal alveoli. Type II pneumocytes were found to be linearly located along these thick elastic fibers. This previously undisclosed distribution of type II pneumocytes may be concerned with alveolar rapid movement.

Adult↗

PubMed2000

Helicobacter pylori infection produces expression of a secretory component in gastric mucous cells.

Helicobacter pylori infection induces the expression of a secretory component (SC) in gastric epithelial cells. We investigated the cell lineage of the SC- and immunoglobulin (Ig) A-expressing epithelial cells in H. pylori-infected gastric mucosa. Materials were obtained by means of gastric biopsy from H. pylori-infected patients (24 cases) before and after the eradication of H. pylori, from five normal uninfected volunteers, and from three gastrectomy cases. Acetic acid-ethanol-fixed and paraffin-embedded specimens were examined using histochemical staining for gastric mucins (periodic acid oxidation-thionine Schiff reaction-concanavalin A-horse radish peroxidase staining) by means of immunostaining for gastric mucins (45M1 and HIK1083), intestinal cells (MUC2 and CD10), Ki67, H. pylori, SC, and IgA. The SC and IgA were not found in normal gastric mucosa. The expressions of the SC and IgA in gastric surface mucous cells and mucous neck cells in the generating zone of the gastric mucosa of H. pylori-infected patients were significantly higher before eradication of H. pylori than after the eradication. These mucous cells have the potential for SC-mediated translocation of IgA into the gastric lumen, and this may act as part of the antibacterial defense system against H. pylori infection in the gastric generating zone.

Adult↗

PubMed2000

Transforming growth factor-alpha stimulates prostaglandin generation through cytosolic phospholipase A(2) under the control of p11 in rat gastric epithelial cells.

The regulatory effects of transforming growth factor (TGF)-alpha on phospholipase A(2) (PLA(2)) isozymes contributing to prostaglandin generation in rat gastric epithelial RGM1 cells were examined. Stimulation with TGF-alpha for 24 h time-dependently induced prostaglandin E(2) generation with an increase in cyclo-oxygenase-2 protein. The TGF-alpha-induced prostaglandin E(2) generation was suppressed by NS-398, a cyclo-oxygenase-2 inhibitor. TGF-alpha stimulated the activity and the protein synthesis of cytosolic PLA(2) (cPLA(2)). A time-dependent increase in cPLA(2) protein occurred in parallel with PGE(2) generation, which was inhibited by methyl arachidonyl fluorophosphonate (MAFP), a cPLA(2) inhibitor. However, no change in activity of secretory PLA(2) or Ca(+2)-independent PLA(2) was observed in the TGF-alpha-stimulated cells. Stimulation with the Ca(2+) ionophore A23187 for 10 min induced MAFP-sensitive arachidonic acid liberation. Interestingly, preincubation with TGF-alpha for 24 h diminished A23187-stimulated arachidonic acid liberation despite the increase in cPLA(2) protein. Under the conditions, TGF-alpha was found to increase p11, an endogenous cPLA(2) suppressor, also known as annexin II light chain. The TGF-alpha-induced increase in p11 was suppressed by tyrphostin AG1478, an inhibitor of tyrosine kinase of epidermal growth factor receptor, which was also found to restore the inhibition by TGF-alpha of A23187-stimulated arachidonic acid liberation. However, TGF-alpha did not alter protein levels of annexin II heavy chain. These results suggest that TGF-alpha stimulates prostaglandin generation through an increase in cPLA(2), the hydrolytic action of which may be under the control of p11.

Animals↗