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Ulcerative colitis (UC) is an immune disorder of the gastrointestinal tract which has been reported to be precipitated by interferon (IFN) therapy. We describe the results of a literature review of cases in which the development or exacerbation of UC was coincident with IFN and/or ribavirin (RIB) treatment for chronic hepatitis C. We summarized the studies on the effectiveness of IFN for UC or Crohn's disease, which were primarily carried out in Europe and the USA. In the nine reported cases of UC exacerbation by IFN therapy in Japan, seven involved IFN-α, one involved IFN-α2b plus RIB, and the other involved IFN-β; thus cases induced by IFN-α were more common. The period between the initiation of IFN treatment and the development or exacerbation of UC varied widely among the reported cases (from 1 day to 4.5 years). The reports have all assumed a cause-and-effect correlation between IFN treatment and UC. However, although combination therapy of IFN and RIB has become widespread in Japan, UC development or exacerbation induced by IFN has not increased concurrently. Conversely, numerous studies reporting the effectiveness of IFN for treating UC and Crohn's disease have been published in Europe and the USA. One reason for this finding may be the difference in the balance of T helper cell 1 and T helper cell 2 between populations.

A 65-year-old woman with liver injury was referred to our hospital in 1992. She was diagnosed with primary biliary cirrhosis (PBC) of Scheuer's histological classification stage IV. She was treated with 600 mg/day of ursodeoxycholic acid. A 1-cm mass in S7 was detected in August 1995. The serum alpha-fetoprotein (AFP) level increased to 1288 ng/mL in January 1996. Angiography showed a cotton wool-like appearance in the delayed phase. Because the size of the tumor appeared to be increasing and the serum AFP levels increased with high levels of L3 fraction, a pelioid-type hepatocellular carcinoma (HCC) was strongly suspected. Hepatic artery infusion with SMANCS and partial resection of S7 and S8 of the liver were performed in March 1996. The pathological diagnosis for theresected liver tumor was pelioid-type HCC. The serum AFP level decreased to 50 ng/mL after the operation, but relapsed HCC was detected in S6 and S7. Angiography in September 1996 revealed multiple hypervascular lesions, and hepatic artery infusion with SMANCS was again performed; however, we were unable to suppress the progression of the relapsed HCC. The patient died due to an intra-abdominal rupture of relapsed HCC and subsequent liver failure in December 1996. We report a rare case of pelioid-type HCC with numerous eosinophilic infiltrations arising from PBC.

Levels of prekallikrein and HMW kininogen that had increased during pregnancy decreased with start of labor. The role of the kinin-forming system with oxytocin in the mechanism of labor was suggested from the results of decreased prekallikrein and HMW kininogen, appearance of a free kallikrein-like enzyme during labor, and from the case of arrested labor in which both prekallikrein and HMW kininogen were markedly decreased. Prekallikrein was markedly decreased in patients with acute obstetrical DIC and severe toxemia of pregnancy. The excessive activation of prekallikrein in DIC seemed to be of help for understanding such clinical signs as shock, abnormal labor, and increased permeability in obstetrical DIC.

Clinical background and incidence of hepatocellular carcinoma (HCC) of patients with chronic hepatitis C who obtained biochemical remission without eradication of virus (biochemical response) after interferon (IFN) treatment was retrospectively analyzed for 755 patients. Annual incidence of HCC was significantly lower in the patients with biochemical response and sustained response than that of the patients that did not show these responses. Logistic regression analysis showed that only the normalization of alanine aminotransferase (ALT) value at the end of IFN treatment was a significant factor for biochemical response. Annual incidence of HCC was significantly lower in the patients who obtained normalization of ALT values at the end of treatment than those who did not. Patients who were younger, who had a lower level of activity and fibrosis indices in histology, higher platelet count, and who were given more higher total dose of IFN were more likely to attain normalization of ALT levels at the end of treatment, and this was related to biochemical response. Low incidence of HCC in patients who obtained normalization of ALT values at the end of treatment was likely because they were in the earlier stage of chronic hepatitis. Active treatment of chronic hepatitis C with interferon in the early phase of the disease may bring about a biochemical response in some patients, even if sustained virological response is not obtained.

A retrospective multicenter analysis of 652 patients with chronic hepatitis C who have been treated with interferon (IFN) was performed to assess the effects of IFN on the clinical course and development of HCC. During a mean follow-up of 54.8 months, hepatocellular carcinoma (HCC) developed in 7.0% of the patients. The rate was significantly higher in the patients who did not respond to IFN treatment than in those with sustained virological response and those who obtained a normalization of alanine aminotransferase levels despite the presence of HCV RNA (incomplete response) (P < 0.01). Using multivariate Cox's proportional hazard model, alcohol abuse (P < 0.05) and a higher level of fibrosis (P < 0.05) before treatment were the significant background factors associated with HCC development in the patients who did not respond to IFN. Interestingly, a significant increase in the rate of HCC development occurred in patients who had a histological finding of progressive fibrosis (F3). In addition, patients with low histological staging scores were likely to have an incomplete response, even if a sustained virological response was not obtained. IFN produced an improvement in histological activity and fibrosis stage in the second biopsy specimens irrespective of the clinical outcome when compared against untreated subjects.

Primary duodenal MALT lymphoma (MALToma) is a very rare neoplasm arising from the mucosa-associated lymphoid tissue of the duodenum. We report a 55-year-old woman with MALToma located in the descending duodenum and accompanying Helicobacter pylori infection of the stomach. We performed operative resection due to involvement of the papilla of Vater and submucosal tumor infiltration. Despite wide mucosal spreading, postoperative examination revealed only a small amount of MALToma cells infiltrating into the submucosa. No invasion into the adjacent structure or metastasis to regional lymph nodes was confirmed, suggesting the disease could have been controlled by eradication of Helicobacter pylori.

症例は42歳,男性.30歳頃より1日ウイスキー500mlから600mlを飲酒.1991年1月,腹部膨満感が出現し当科受診,黄疸と多量の腹水を認め,アルコール肝硬変と診断された.CT,USでは,多量の腹水と脾腫を認め99mTc-phytateシンチではRIの肝への取り込みは不良であった.断酒により黄疸,腹水が消失,以後外来にて経過観察していたが,1994年6月,99mTc-phytateおよび99mTc-GSAシンチでは右葉を中心とした多発するSOLを認め,CTでは内部densityの不整が出現し肝細胞癌あるいは転移性肝癌が考えられた.しかし,AFP, PIVKA-IIは陰性で,US,腹部血管造影でも腫瘤性病変は認められなかった.本症例は大量飲酒のために網内系細胞,肝細胞が広範に脱落したが,禁酒により限局性の大きな瘢痕組織を残して回復に向かったため,肝シンチで特異なSOLを呈した稀な1例と考えられた.

A case of malignant melanoma arising in uterine cervix of a 68-year-old woman is reported. The tumor had giant cells with bizarre nuclei, prominentnucleoli, abnormal cytoplasm and melanin pigment.Immunocytochemically, tumor cells revealed expression of HMB-45. Cytology and immunocytochemistry were very effective for diagnosis and to understand biological behavior in the tumor.

手術不能と診断された進行肝細胞癌28例(塊状型19例,びまん型5例,結節型4例)に対して温熱療法を中心とした集学的治療法を施行しその抗腫瘍効果について検討した.方法は13.56MHz RF誘電加温装置を用い,1回/週,40分間,計10回の加温を原則とした.加温中はMMC, 5-FUなどによる全身化学療法を,加温前後には可能な限りTAE, LPD動注を含むone shot動注療法を併用した.腫瘍の退縮に基づく評価により温熱療法の抗腫瘍効果を検討すると28例中4例(14%)にPRを認めたがその4例はいずれも男性でProtocol通りの充分な加温可能であった症例であり,その肉眼分類は塊状型で,臨床病期ではIが1例,IIが3例と比較的良好な肝機能を有する症例であった.脈管浸潤の程度ではVp2が3例,Vp3が1例であった.また,結節型,びまん型ではその治療効果は極めて不充分であった.

Ulcerative colitis (UC) is an immune disorder of the gastrointestinal tract which has been reported to be precipitated by interferon (IFN) therapy. We describe the results of a literature review of cases in which the development or exacerbation of UC was coincident with IFN and/or ribavirin (RIB) treatment for chronic hepatitis C. We summarized the studies on the effectiveness of IFN for UC or Crohn's disease, which were primarily carried out in Europe and the USA. In the nine reported cases of UC exacerbation by IFN therapy in Japan, seven involved IFN-α, one involved IFN-α2b plus RIB, and the other involved IFN-β; thus cases induced by IFN-α were more common. The period between the initiation of IFN treatment and the development or exacerbation of UC varied widely among the reported cases (from 1 day to 4.5 years). The reports have all assumed a cause-and-effect correlation between IFN treatment and UC. However, although combination therapy of IFN and RIB has become widespread in Japan, UC development or exacerbation induced by IFN has not increased concurrently. Conversely, numerous studies reporting the effectiveness of IFN for treating UC and Crohn's disease have been published in Europe and the USA. One reason for this finding may be the difference in the balance of T helper cell 1 and T helper cell 2 between populations.

A 64-year-old man who had been given a diagnosis of idiopathic chronic cold agglutinin disease in a medical clinic suffered from Raynaud's phenomenon and acrocyanosis in winter. He was admitted to our hospital with unbearable abdominal pain. Blood tests showed liver dysfunction with jaundice and severe acidosis. Abdominal angiogram and contrast-enhanced CT revealed superior mesenteric artery occlusion. These findings suggest that thrombosis due to cold agglutinin disease could be the cause of superior mesenteric artery occlusion.

A 75-year-old female, who had an abnormal stomach x-ray finding, was admitted to the hospital for further examination and therapy. Upper GI endoscopy showed reddish and swollen folds on the greater curvature of the gastric body and a biopsy was of this lesion revealed malignant lymphoma (small cell type or mucosa-associated lymphoid tissue (MALT) lymphoma suspected). The patient was infected with Helicobacter pylori ( H. pylori), however, in response to the patient's wishes, a total gastrectomy, omentectomy and splenectomy were performed and the histological diagnosis was gastric MALT lymphoma. Two courses of CHOP therapy (cyclophosphamide (CPM) 750 mg/m2/day, day 1, adriamycin (ADM) 50 mg/m2/day, day 1, vincristine sulfate (VCR) 1.4 mg/m2/day, day 1, prednisolone 100 mg/body, day 1–5) were administered as adjuvant chemotherapy. A colonoscopic examination performed about 4.5 yr after the operation revealed rectal submucosal tumors and the biopsied specimens were diagnosed as malignant lymphoma. A transanal focal resection was performed and the histological diagnosis was metachronous and ectopic development of MALT lymphoma. The histological finding was similar to the gastric lesion. About 4 and 7 yr after the first development of rectal MALT lymphoma, MALT lymphomas developed repeatedly in the rectal lesion, however, these were resected repeatedly and no developmenthas occurred during the past two years. This report presents a very rare case of metachronous and ectopic MALT lymphoma development in the gastric and rectal lesions.

A 59-year-old man diagnosed as gastric cancer with peritonitis carcinomatosa was treated with paclitaxel and TS-1; 60 mg/m(2)/day of paclitaxel was given on days 1 and 8, and 60-80 mg/m(2)/day of TS-1 was given for 2 weeks. Six courses of combination therapy were administered, and the ascites disappeared completely. Because multiple bone metastases occurred, we attempted combination therapy with cisplatin and irinotecan hydrochloride; 50 or 30 mg/m(2)/day of cisplatin was given on day 1 or day 15, and 70 mg/m(2)/day of irinotecam hydrochloride was given on days 1 and 15. The patient achieved a remarkable response, however, intrameningeal dissemination occurred and he died from rapidly progressive meningitis carcinomatosa.

AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)]. Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 ± 12 mo in AIH patients and 8.4 ± 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC.

A 60-year-old man, who had been admitted to another hospital with complaints of constipation, abdominal fullness and appetite loss, was referred to our hospital for further examination and therapy. The patient was diagnosed as advanced gastric cancer (type-3) with multiple liver metastasis and obstructive jaundice. He was treated with combination therapy of paclitaxel and TS-1 (60 mg/m(2)/day of paclitaxel was iv administered on day 1 and 8, and TS-1 of 80 mg/m(2)/day was orally administered for 2 weeks followed by one drug-free week), and showed a remarkable response. However, because of ascites, elevated serum CEA level and resistance in the liver metastasis and gastric region, we attempted two courses of combination therapy with high-dose CPT-11 and cisplatin (70 mg/m(2)/day of CPT-11 was administered iv on day 1 and 15, and 80 mg/m(2)/day of cisplatin on day 1 followed by two drug-free weeks) which showed a remarkable response. Two courses of combination therapy with low-dose CPT-11 and cisplatin (60 mg/m(2)/day of CPT-11 and 30 mg/m(2)/day of cisplatin were administered iv on day 1 and 15 followed by two drug-free weeks) on an outpatient basis. However, the patient showed resistance to the latter combination therapy, increased ascites due to suspicious peritonitis carcinomatosa and obvious re-growth of the metastatic tumors in the liver. He died on May 23, 2006, about ten months after initial diagnosis. We reported a case of successful treatment of combination chemotherapy for advanced gastric cancer with obstructive jaundice due to progressive multiple metastatic tumors in the liver and obtained comparative long-term survival maintaining high quality of life.

A 55-year-old man with chronic hepatitis C had diarrhea with bloody stool in July, 2003 and ulcerative colitis was suspected. However, he quickly improved. He was treated with percutaneous radiofrequency ablation therapy for adenomatous hyperplasia in S5 of the liver in December, 2004. After the ablation therapy, he was treated with combination therapy of PEG-interferon alpha-2b and ribavirin for chronic hepatitis C. Because exacerbation of ulcerative colitis appeared 10 weeks after beginning of the treatment for hepatitis C, the combination therapy of PEG-interferon and ribavirin was discontinued. He was treated with mesalazine and steroid therapy for ulcerative colitis, and improved. We report the first case in Japan of the exacerbation of ulcerative colitis induced by the combination therapy of PEG-interferon and ribavirin for chronic hepatitis C.

Clinical background and incidence of hepatocellular carcinoma (HCC) of patients with chronic hepatitis C who obtained biochemical remission without eradication of virus (biochemical response) after interferon (IFN) treatment was retrospectively analyzed for 755 patients. Annual incidence of HCC was significantly lower in the patients with biochemical response and sustained response than that of the patients that did not show these responses. Logistic regression analysis showed that only the normalization of alanine aminotransferase (ALT) value at the end of IFN treatment was a significant factor for biochemical response. Annual incidence of HCC was significantly lower in the patients who obtained normalization of ALT values at the end of treatment than those who did not. Patients who were younger, who had a lower level of activity and fibrosis indices in histology, higher platelet count, and who were given more higher total dose of IFN were more likely to attain normalization of ALT levels at the end of treatment, and this was related to biochemical response. Low incidence of HCC in patients who obtained normalization of ALT values at the end of treatment was likely because they were in the earlier stage of chronic hepatitis. Active treatment of chronic hepatitis C with interferon in the early phase of the disease may bring about a biochemical response in some patients, even if sustained virological response is not obtained.

A case of vulvar adenocarcinoma in a 76-year-old woman is reported.The tumor has cribriform and “Comedo” like pattern in histology, polyhedral aggregate and prominent nucleoli in cytology, which are similar to those in breast carcinoma.Tumor cells revealed, expression not only of epithelial membrane antigen, keratin and carcinoembryonic antigen, but also of human papilloma virus antigen and estrogen receptor. Further, many tumor cells showed a strong staining of proliferating cell nuclear antigen. In this report, possible origin and biological behavior of the tumor are discussed.

This paper describes a design approach and its implementation for a broadband access management system that provides element and network management functions for FTTC (fiber-to-the-curb)/FTTB (fiber-to-the-building) access networks, and service management functions for video on demand (VOD) services. The proposed architecture is a top-down approach, and consists of four levels of basic architecture, namely, service/functional architecture, system architecture, network architecture and software architecture. By the proposed architecture, TMN compliant layered management functions are realized for the broadband access system at EML (element management layer), NML (network management layer) and SML (service management layer). By considering multi-vendor environments, the proposed management systems communicate each other via OSI protocols. Three different configurations are evaluated for EML agents, and the distributed or hybrid EML agent approaches are cost effective solutions based on current technologies. Finally, this paper shows a prototype system based on the proposed architecture.

A retrospective multicenter analysis of 652 patients with chronic hepatitis C who have been treated with interferon (IFN) was performed to assess the effects of IFN on the clinical course and development of HCC. During a mean follow-up of 54.8 months, hepatocellular carcinoma (HCC) developed in 7.0% of the patients. The rate was significantly higher in the patients who did not respond to IFN treatment than in those with sustained virological response and those who obtained a normalization of alanine aminotransferase levels despite the presence of HCV RNA (incomplete response) (P0.01). Using multivariate Cox's proportional hazard model, alcohol abuse (P0.05) and a higher level of fibrosis (P0.05) before treatment were the significant background factors associated with HCC development in the patients who did not respond to IFN. Interestingly, a significant increase in the rate of HCC development occurred in patients who had a histological finding of progressive fibrosis (F3). In addition, patients with low histological staging scores were likely to have an incomplete response, even if a sustained virological response was not obtained. IFN produced an improvement in histological activity and fibrosis stage in the second biopsy specimens irrespective of the clinical outcome when compared against untreated subjects.

A 59-year-old woman suspected of having colonic malignant lymphoma was transferred to our hospital (Japan Labour Health and Welfare Organization Tsubame Rosai Hospital, Tsubame, Niigata, Japan) in October 2003. Systemic CT scan showed no swollen lymph nodes. Gallium scintiscan useful in localising lymphoma, showed no abnormal accumulation. Endoscopic findings of the oesophagogastroduodenal tract showed no tumour lesions. Colonoscopic examination was performed in November 2003, and clearly revealed multiple small elevations (fig 1A). Endoscopic mucosal resections were performed on lesions and the resected specimens suggested mantle cell lymphoma (MCL). A second colonoscopic examination performed in July 2004 revealed increased numbers of polyps, indicating a case of multiple lymphomatous polyposis (MLP). Biopsy was performed again to confirm the diagnosis of colonic MCL. Figure 1B–D shows the histopathological findings of both resected and biopsy specimens. Immunohistochemical examination of these specimens revealed positive immunoreactivity for CD20 and CD5 (fig 1E), and negative …

A 55 year old man with chronic hepatitis C presented with diarrhoea and bloody stools in July 2003. Colonoscopic examination showed redness and oedematous mucosa in the rectum and ulcerative colitis was suspected. Biopsy of the lesion confirmed the diagnosis and treatment was initiated with mesalazine (5-ASA 2250 mg/day). However, he showed short term improvement and mesalazine was discontinued. He was treated with percutaneous radiofrequency ablation therapy (RFA)(Cool-tip) for adenomatous hyperplasia in S5 of the liver in December 2004. After providing consent to treatment with interferon (IFN), the patient underwent combination therapy with PEG-IFNα-2b (100 mg/week) and ribavirin (800 mg/day) for chronic hepatitis C. Liver biopsy and blood biochemistry revealed chronic active hepatitis C virus (HCV) F3/A2, genotype 1b, liver injury associated with HCV, aspartate aminotransferase (AST) 109 IU/l, alanine aminotransferase (ALT) 126 IU/l, and HCV RNA 3400.0 KIU/ml (by reverse transcription nested polymerase chain reaction, high range method). One …

As a result of having undergone computed tomography (CT), a 75-year-old woman with type-C liver cirrhosiswas shown to have two tumors on the ventral and dorsal sides of subsegment 3 (S3). The tumor on the ventral side was diagnosed as a classic hepatocellular carcinoma (HCC), while that on the dorsal side was considered atypical for a HCC. Although the indocyanine green (ICG) findings indicated poor hepatic reserve, the prothrombin time (PT) was relatively good. An operation was performed in February 2007; however, this resulted in exploratory laparotomy. Dynamic CT performed 12 mo after the operation revealed that the tumor on the dorsal side of S3 had apparently increased. The marginal portion of the tumor was shown to be in the early and parenchymal phases, while the internal portion was found to have grown only slightly in the delayed phase. We diagnosed this tumor as a cholangiocellular carcinoma (CCC). S3 subsegmentectomy was performed in April 2008. The tumor on the ventral side was pathologically diagnosed as a moderately differentiated HCC, and that on the dorsal side was diagnosed as a CCC. We can therefore report a rare case of synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type-C liver cirrhosis. We also add a literature review for all the reported cases published in Japan and around the world, and summarize the features of double cancer exhibiting both HCC and CCC.

A pedigree of cancer family syndrome with an aggregation of transitional cell cancer (TCC) of the urinary tract is reported. The proband had left (lt) pelvic cancer at the age of 49, and double cancers of the right (rt) fallopian tube and the uterine body at 50. Various types of cancer, including colon cancer and gastric cancer, were found in four out of her seven siblings. In three siblings, TCC of the urinary tract was found. Although TCC has not been described to be a cancer found in cancer family syndrome, this pedigree clearly demonstrates that TCC is one such cancer.

In order to clarify the mechanism of DIC, the kinin-forming enzyme system which relates to bothcapillary permeability and blood coagulation was studied. Prekallikrein was determined by TAMe-or BAMe-lytic method.The results obtained were as follows:1. To obtain sufficient activation of prekallikrein to kallikrein, the concentration of factor XII was necessary to be more than 40%.2. Since hemolysis caused the activation of prekallikrein, artifact hemolysis should be avoided.3. BAMe was approximately 10 times more sensitive than TAMe.4. Prekallikrein content was significantly lowered in the patients with obsterical acute DIC. This might be due to consumption. The activation of prekallikrein to kallikrein causes enhanced capillary permeability and lowered function of blood coagulation, and aggravates DIC with vitious cycle.

It has been a general concept that fibrinolytic activity is diminished during pregnancy. However, increase in FDP (fibrin/fibrinogen degradation products by plasmin digestion) which indicates accelerated fibrinolytic activity is also observed during pregnancy. To clarify these conflicting findings, alpha-2-plasmin inhibitor and FDP, sensitive indicators of fibrinolytic activity, were studied during pregnancy. Decrease in plasmin inhibitor and increase in FDP were found during pregnancy suggesting that fibrinolytic activity is accelerated during pregnancy. Since FDP level was higher in blood samples from the uterine vein than those from the artery, the accelerated fibrinolysis characterized by decrease in plasmin inhibitor and increased FDP, might be reflection of local event. On the other hand, systemic blood remains still hypofibrinolytic in normal pregnant condition.

From the standpoint of labor mechanism, behavior of prekallikrein, a kinin-forming enzyme, during pregnancy and labor has been of great importance. Plasma prekallikrein determined by synthetic chromogenic tripeptide substrate was increased with advancing gestational ages, reaching approximately 200% of normal. When labor started, it decreased rapidly to 70%, then returned gradually to the normal level after delivery. Prekallikrein and kininogen are only two plasma proteins which change so markedly during labor among many plasma proteins. Role of prekallikrein in the mechanism of labor is presumptively as follows: (1) Prekallikrein is converted to kallikrein resulting in its consumption and decrease. (2) Kallikrein contributes to uterine contraction by liberating kinin from kininogen.

KOJIMA, N., ISEMURA, M., YOSIZAWA, Z., ONO, T., SHINADA, S., SOGA, K., AOYAGI, Y. and ICHIDA, F. Distribution of Fibronectin in Fibrotic Human Livers at Various States. Tohoku J. exp. Med., 1981, 135 (4), 403-412-Fibronectin was isolated from human plasma by affinity chromatograpy with gelatin-coupled Sepharose 4B. Anti-fibronectin antiserum was prepared using rabbits, and human liver biopsy specimens at various stages of fibrosis were investigated for distribution of fibronectin by the indirect immunofluorescence technique. Fibronectin was absent in liver parenchymal cells, while it was detected intensely in reticulin and the area containing collagen fibers. The existence of fibronectin in the necrotic area and in prematured fibers suggests the earlier deposition of fibronectin than that of collagen at the locus of tissue repairing, and thus the important role of fibronectin at the early stage of fibrosis.-fibronectin; liver fibrosis; collagen: immunofluorescence