Akira Terano

Percutaneous ethanol injection therapy for hepatocellular carcinoma. A histopathologic study

Histopathologic examination was done on 18 cases after percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma. In eight cases, the lesion was treated by PEIT alone; in the other ten cases, PEIT was combined with transcatheter arterial embolization. The lesion was completely necrotic in 13 cases, 90% necrotic in four cases, and 70% necrotic in the rest. In addition, PEIT seemed to be effective against intercapsular, extracapsular, and vascular invasions. In the four cases of incomplete necrosis, the viable cancer tissue remained in small tumor nodules around the main tumor, in portions isolated by septa, or along the edge of the lesion. Therefore, ethanol should be injected not only into the center of the lesion, but also into sites close to its edge. Ethanol did not damage noncancerous liver parenchyma distant from injected sites. Local dissemination of the cancer cells was not found in any case. Therefore, PEIT seems to be a valuable therapy and may be an alternative to surgery in some cases.

Two different promoters direct expression of two distinct forms of mRNAs of human platelet-activating factor receptor

The human platelet‐activating factor (PAF) receptor gene exists as a single copy on chromosome 1. We identified two 5′‐noncoding exons, each of which has distinct transcriptional initiation sites. These exons are alternatively spliced to a common splice acceptor site on a third exon that contains the total open reading frame to yield two different species of functional mRNA (Transcript 1 and 2). Transcript 1 has consensus sequences for transcription factor NF‐κB and Sp‐1, and the Initiator (Inr) sequence homologous to the murine terminal deoxynucleotidyltransferase gene. Transcript 2 also contains consensus sequences for transcription factor AP‐1, AP‐2, and Sp‐1. Transcripts 1 and 2 were both detected in heart, lung, spleen, and kidney, whereas only Transcript 1 was found in peripheral leukocytes, a differentiated human eosinophilic cell line (EoL‐1 cells), and brain. Existence of distinct promoters was thus suggested to play a role in the regulatory control of PAF receptor gene expression in different human tissues and cells.

Protection of cultured rat gastric cells against oxidant-induced damage by exogenous glutathione

BACKGROUND/AIMSnReduced glutathione (GSH) is an intracellular protectant against oxidants. The present study determined whether extracellular GSH protects against oxidant damage or whether an uptake system of GSH is present in cultured gastric cells.nnnMETHODSnHydrogen peroxide was generated by glucose oxidase and glucose. Cytotoxicity was assessed by 51Cr release. Intracellular GSH was assayed by the method of Tietze.nnnRESULTSnPretreatment with extracellular GSH decreased H2O2-induced 51Cr release. Treatment with GSH enhanced cellular GSH content. Protection by pretreatment with GSH was prevented by buthionine sulfoximine (an inhibitor of gamma-glutamylcysteine synthetase). Enhancement of intracellular GSH was also prevented by buthionine sulfoximine. Acivicin (an inhibitor of gamma-glutamyl transpeptidase) prevented intracellular accumulation of GSH from extracellular GSH. Cysteine was effective in preventing damage and enhancing intracellular GSH content, whereas both glutamine and glycine were not.nnnCONCLUSIONSnExtracellular GSH protects cultured gastric cells from H2O2 damage by accelerating intracellular GSH synthesis; this is mediated by membrane-bound gamma-glutamyl transpeptidase acting on extracellular GSH (which supplies these cells with cysteine) and then by intracellular gamma-glutamylcysteine synthetase.

Role of Superoxide and hydroxyl radicals in rat gastric mucosal injury induced by ethanol

SummaryIt has been reported that oxygen-derived free radicals play an important role in the pathogenesis of mucosal injury in the small intestine as well as in the stomach. The aims of this study were to test whether ethanol-induced damage in the rat stomach was prevented by the administration of (1) Superoxide dismutase (SOD; a scavenger of Superoxide radicals), (2) allopurionol (ALP; an inhibitor of xanthine oxidase), (3) dimethyl sulfoxide (DMSO; a scavenger of hydroxyl radicals). SOD significantly decreased the ulcer index from 100±8.5% (control) to 39.6±8.2% (P<0.001). Ethanol-induced damage was reduced by the administration of ALP by 37.4% (P<0.01). DMSO also diminished the ulcer index from 100±8.5% (control) to 31.6±5.8% (P<0.01). Histochemical studies supported these results. A scanning EM study, however, revealed that surface epithelial cells were not protected by SOD against ethanol-induced damage. These results demonstrated that SOD, ALP and DMSO had the ability to protect gastric mucosa against ethanol-induced injury. Accordingly, oxygen-derived free radicals may be involved in the pathogenesis of ethanol-induced gastric mucosal damage. Surface epithelial cells, however, were not protected even by SOD against ethanol-induced injury.

Chemokine expression in Helicobacter pylori-infected gastric mucosa.

Abstract: Inflammatory response to Helicobacter pylori is characterized by infiltration of neutrophils, monocytes, and lymphocytes into the gastric mucosa. Interleukin-8 (IL-8), a prototype of the CXC-chemokine subfamily, may be a key modulator in inducing neutrophil migration and activation in H. pylori-infected gastric mucosa. IL-8 is produced by gastric epithelial cells in response to H. pylori infection, and IL-8 expression is induced by local production of proinflammatory cytokines and attachment of H. pylori organisms to the gastric epithelial cell surface. Multiple genes in the H. pylori cag pathogenicity island seem to be involved in inducing the epithelial IL-8 response to H. pylori attachment. Activation of the transcription factor, nuclear factor κB (NF-κB), is associated with this IL-8 response. Reactive oxygen intermediates whose production is increased in H. pylori-infected gastric mucosa may also modulate IL-8 expression in the gastric mucosa. Recent reports also suggest that the local production of CC-chemokines, another chemokine subfamily, is important in H. pylori-associated gastritis.

Redox Regulation of Interleukin-8 Expression in MKN28 Cells

Recent evidence suggests a role of reactiveoxygen intermediates (ROI) in intracellular signalingand regulation of gene expression. We examined whetherexpression of interleukin-8 (IL-8), a key cytokine in the inflammatory responses of gastricepithelial cells, is sensitive to antioxidants andoxidative stress. IL-8 secretion was quantified by IL-8enzymelinked immunosorbent assay, and IL-8 mRNAexpression was determined by northern blot analysis.Electrophoretic mobility shift assay was performed todetect the transcription factor, nuclear factor κB(NF-κB). N-Acetylcysteine (NAC) ordimethylsulfoxide inhibited IL-8 expression induced by tumornecrosis factor-α (TNF-α) orinterleukin-1β (IL-1β). Externally appliedH2O2 significantly up-regulatedIL-8 expression. TNF-α-induced activation of NF-κB activity was suppressed by NAC,and H2O2 caused significantactivation of NF-κB. Since ROI production isincreased in the inflamed gastric mucosa, for example,in H. pylori-associated gastritis, the present results suggest that ROImay be an important modulator of IL-8 expression ingastric mucosal cells.

Churg-Strauss syndrome (allergic granulomatous antiitis) with multiple perforating ulcers of the small intestine, multiple ulcers of the colon, and mononeuritis multiplex

A case of Churg-Strauss syndrome with multiple perforations of the small intestine is described. A 31-year-old woman was admitted with a complaint of epigastric pain. She had a history of bronchial asthma. One week before admission, white blood cell count was 20 800/mm3 with 59% eosinophils. Neurological examination on admission disclosed mononeuritis multiplex with paresthesia in both the lower and upper extremities. At colonoscopy, there were scattered aphthous ulcers in the colon. Ophthalmological examination revealed allergic conjunctivitis. After admission, hypereosinophilia increased to as high as 36 000/mm3. Oral administration of prednisolone (60 mg/day) was begun. On the 3rd day of the treatment, the eosinophil count decreased dramatically, to 400/mm3, while severe abdominal pain developed. Since abdominal X-ray film revealed free air in the abdominal cavity, emergency laparotomy was performed and multiple intestinal ulcers with perforations were found. Partial ileectomy was performed. Pathological findings of the resected specimen were interpreted as a necrotizing angiitis with extravascular granuloma. Since the operation, the patient has been asymptomatic, except for neurological symptoms. Hypereosinophilia has decreased without treatment to counts averaging 270/mm3, within 3 months. On the basis of the clinical features and histopathological findings, a diagnosis of Churg-Strauss syndrome was established.

Multiple-needle insertion method in percutaneous ethanol injection therapy for liver neoplasms

SummaryOne of the shortcomings of percutaneous ethanol injection therapy (PEIT) is that many sessions are necessary to accomplish the treatment. In order to reduce the number of treatment sessions, we inserted two or three needles before injection of ethanol was begun. Using the multiple-needle insertion method, we markedly reduced the number of treatment sessions. Histopathologic examination, imaging techniques, and serum alpha-fetoprotein levels showed efficacy of PEIT using the multiple-needle insertion method. No serious complication occurred. Levels of transient pain, fever, and the feeling of intoxication did not seem to be different from those occurring with the conventional method. Multiple-needle insertion method may be valuable as a method for reducing the number of treatment sessions necessary and thus shortening the treatment period.

Massive gastrointestinal hemorrhage in systemic lupus erythematosus: successful treatment with corticosteroid pulse therapy

Although mesenteric vasculitis due to systemic lupus erythematosus (SLE) is relatively uncommon, it is the most dangerous manifestation associated with high mortality. We describe the case of a SLE patient with life-threatening gastrointestinal hemorrhage due to mesenteric vasculitis in whom methylprednisolone pulse therapy was quite effective in controlling the hemorrhage and resulted in a satisfactory long term outcome. A 47-yr-old woman presenting with high fever, rash, and melena was diagnosed with SLE from positive antinuclear antibodies, anti-dsDNA, and low complement titers. Although fever and rash subsided with administration of prednisolone, massive hematemesis appeared with melena. Endoscopy demonstrated bleeding ulceration of the antrum, which was intractable despite intensive antiulcer therapy and transfusion. Surgical exploration revealed ileal penetration, and multiple bleeding ulcerations were observed over the resected ileum as well as the antral ulceration. However, bleeding persisted after surgery and surgical findings prompted us to select methylprednisolone pulse. Hemorrhage responded promptly to the therapy, and the patient has remained well since then for >10 yr. Our report indicates that corticosteroid pulse may serve as one of the therapeutic options for SLE with massive hemorrhage due to widespread mesenteric vasculitis.

Protective effect of tauroursodeoxycholate against chenodeoxycholate-induced damage to cultured rabbit gastric cells

Ursodeoxycholate (UDC) and tauroursodeoxycholate (TUDC) have been reported to be protective against liver injury induced by other bile salts. UDC also has been shown to be effective against refluxed bile-induced gastritis after gastric surgery. However the mechanism of the therapeutic effect of UDC on gastric mucosa has not been known. In the present study, cytoprotective actions of UDC and TUDC against chenodeoxycholate (CDC)-induced gastric injury were investigated using rabbit gastric cell cultures without systemic factors. Rabbit gastric mucosal cells were cultured after the isolation of rabbit gastric cells with collagenase and ethylenediaminetetraacetic acid. Cytotoxicity was quantified by measuring51Cr release from prelabeled cells and MTT assay. Prostaglandin (PG) E2 was assayed by radioimmunoassay. Concentrations of CDC>0.5mM or UDC>5mM caused cellular damage and increased51Cr release in a dose-dependent and time-dependent fashion, while TUDC up to 10 mM did not. TUDC, but not UDC, showed a significant decrease of CDC (1.5 mM)-induced51Cr release dose dependently. The protective effect of TUDC against CDC-induced damage was confirmed by MTT assay. On phase-contrast microscopy, disruption of monolayers induced by CDC (1.5 mM) was clearly protected by TUDC (10 mM). Free radical scavengers (500 units/ml of superoxide dismutase, 300 units/ml of catalase, and 100 mM of dimethyl sulfoxide) or a calcium blocker (10−7–10−5 M verapamil) did not show significant protection against CDC-induced damage. Deprivation of Ca2+ in the media did not affect CDC-induced damage. Thus free radicals of Ca2+ might not be involved in the cell toxicity of CDC. Although TUDC (10 mM) significantly increased PGE2 production by cultured cells, indomethacin (10−4 M) did not reduce protective effects of TUDC, as assessed by51Cr release and MTT assay. In conclusion TUDC is cytoprotective against CDC-induced damage to cultured rabbit gastric cells. Neither free radicals, Ca2+, nor endogenous PGs may play leading roles in the mechanism of this action.