[A case of primary biliary cirrhosis presenting histopathological similarity to idiopathic portal hypertension with huge splenomegaly].
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Biomedical subjects
Publications and source records attributed to H Isobe.
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A 43-year-old woman was referred for examination because of an abnormal shadow on a chest X-ray film. She had a 12-year history of seropositive rheumatoid arthritis. Chest X-ray films and CT scans showed a pleurabased solitary nodule without a cavity. Cytological examination of a transbronchial biopsy specimen did not lead to a diagnosis, so thoracoscopic enucleation was performed. Histologically, the nodule consisted of lymphocytes and fibroblasts surrounding a central necrotic area, which indicated that it was a rheumatoid nodule. This solitary necrobiotic nodule was radiographically indistinguishable from lung adenocarcinoma, so histologic confirmation was necessary.
A 55-year-old patient with multiple myeloma (IgG-lambda) diagnosed in November 1988 was admitted because of bone pain throughout the body. After plasmapheresis and several courses of chemotherapy, a massive tumor of the left thoracic wall involving the rib appeared. Radiotherapy was performed to ameliorate the severe chest pain, after which myelomatous pleural effusion appeared on the left side. The serum, urine and pleural effusion revealed increased activity of amylase of the salivary type. Amylase activity was also detected in the supernatant of myeloma cells cultured from pleural effusion. We reviewed 12 cases of ectopic amylase-producing multiple myeloma. All the cases except one have been reported from Japan, and hyperamylasemia in these cases was detected at diagnosis or during course of the illness. Moreover, cytogenetic analysis of myeloma cells of previous reports revealed structural abnormalities including chromosome 1, near the amylase gene locus. This case also showed t (1; 10) (q 21?; q 26) by examination of 8 metaphase derived from bone marrow. These observations suggested that ectopic amylase production was induced by irradiation to the plasmacytoma of thoracic wall.
BACKGROUND: Hematogenous metastasis requires angiogenesis within the tumor. Previous studies have shown that microvessel counts in histologic sections of the primary tumor, which reflect angiogenesis, are correlated with metastasis in breast, prostate and Stage I nonsmall cell lung carcinoma. In this study, the authors investigated the association between angiogenesis, hematogenous metastasis and lymph node metastasis in all stages of lung adenocarcinoma. METHODS: Microvessels were highlighted by immunostaining endothelial cells for factor VIII. We counted microvessels within the tumors of 42 patients who had surgical resection (25 with relapse and 11 without relapse more than 5 years after surgical resection). Without knowledge of patient outcome, microvessels were counted on a 200x field (0.723 mm2) in the most active areas of neovascularization. RESULTS: The microvessel counts from patients with relapse after surgical resection (mean +/- standard deviation, 75.4 +/- 64.3) were significantly higher than those without relapse more than 5 years after surgical resection (42.6 +/- 26.0) (P = 0.027). Analysis of regional lymph node metastases (factor N) revealed that the microvessel counts were 62.6 +/- 35.1 for N0 (no regional lymph node metastasis), 51.7 +/- 22.2 for N1 (metastasis in ipsilateral, peribronchial and/or ipsilateral hilar lymph nodes, including direct extension), 75.4 +/- 75.3 for N2 (metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes), and 74.0 for N3 (metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node[s]), and these values were not significantly different from each other. CONCLUSIONS: Angiogenesis assessed by microvessel counts, correlated positively with relapse after surgical resection and hematogenous metastasis in all stages of lung adenocarcinoma; there was no correlation with lymph node metastasis in lung adenocarcinoma.
BACKGROUND: The concentration of cysteine proteinase cathepsin B has been shown to be elevated in association with malignancy or metastatic potential of human and rodent tumors, but its prognostic value for human lung cancer remains undetermined. METHODS: Using a polyclonal antibody, immunohistochemical analyses of cathepsin B were performed on paraffin embedded sections of tumors obtained surgically from 108 patients with non-small cell lung cancer (49 squamous cell carcinomas, 59 adenocarcinomas). The immunohistochemical expressions of cathepsin B in the tumors were compared with patient survival. RESULTS: Higher grade expression of cathepsin B was associated significantly with shorter survival in non-small cell lung cancer (P < 0.01), in squamous cell carcinoma (P < 0.05), and in adenocarcinoma (P < 0.01). A similar result also was seen in Stage I non-small cell lung cancer (P < 0.05). CONCLUSIONS: The authors concluded that the immunohistochemical staining pattern of cathepsin B may be a useful predictor of survival for human lung cancer.
Eight cell lines were established from the pleural effusion of 4 patients with malignant mesothelioma. The most sensitive (FCCMES-4) and the most resistant (FCCMES-2) mesothelioma cell lines had IC50 of 0.66 and 1.85 microM for doxorubicin in clonogenic assays, respectively. In comparison with murine leukemic P388 cells, mesothelioma cell lines were 7.5- to 21-fold more resistant to doxorubicin. Co-incubation with verapamil significantly increased doxorubicin retention in one of the cell lines (FCCMES-2) expressing P-glycoprotein in 16.8% of the cells. These results indicate that doxorubicin resistance may be intrinsic in refractory mesothelioma patients and P-glycoprotein-mediated drug efflux may be involved in resistance of some of the mesotheliomas.
The distributions of cathepsin B (CB) a lysosomal cysteine proteinase, type IV collagen (CIV) and laminin (LM), which are main components of basement membranes (BMs) were studied in a series of 64 human lung adenocarcinomas using an immunohistochemical technique. Over-expression of CB (> 80% positive cells) was significantly associated with the grade of tumour differentiation (p < 0.01), with lymph node metastasis (p < 0.01) and with BM degradation (p < 0.01) detected by the staining pattern of CIV and LM. It was significantly associated with a prognostic disadvantage (p < 0.01). The immunohistochemical staining pattern of CB has a close relationship with degradation of BM, and may be used as a marker for tumour metastasis and prognosis in lung adenocarcinoma.
Using a scintigraphic technique, we investigated gastric emptying of a semisolid meal in 20 patients with liver cirrhosis and in 10 control subjects and correlated gastric emptying with gastrointestinal symptoms and with autonomic nervous function as determined by R-R interval variation on the electrocardiogram. All subjects lacked endoscopic abnormalities that might explain their gastrointestinal symptoms. None had alcoholic liver disease, diabetes, or other diseases known to affect gastric emptying. The half-time for gastric emptying was significantly prolonged in the cirrhotic patients (51.3 +/- 16.6 minutes) as compared with control subjects (29.9 +/- 8.4) (P < 0.01). There was a significant correlation between the gastrointestinal symptom score and the half-time for gastric emptying (r = 0.46, P < 0.05) in the cirrhotic patients. However, the decreases in R-R interval variation and gastric emptying were not significantly correlated. These observations indicate that delayed gastric emptying is frequently present in patients with liver cirrhosis and may produce their gastrointestinal symptoms.
We examined the relationship between the retention of thallium-201 (201Tl) on a delayed scan and the metastatic potential of adenocarcinomas of the lung. We studied 43 patients with adenocarcinoma of the lung and divided them into two groups according to the presence or absence of lymph node metastasis. 201Tl single photon emission computerised tomography (SPECT) was conducted twice: 15 min (early scan) and 120 min (delayed scan) after intravenous injection of 3 mCi of 201Tl chloride. We calculated the retention index in order to evaluate the degree of 201Tl retention in the primary tumour. The retention indices were significantly higher in the group that was positive for lymph node metastasis than in the negative group. In adenocarcinomas with high metastatic potential, 201Tl SPECT demonstrated slow washout or increased retention on the delayed scan. The retention index of 201Tl SPECT is a useful indicator of metastatic potential, thereby facilitating the prediction of prognosis, and provides insight into the relationship between 201Tl uptake and malignancy. This is the first report demonstrating a significant relationship between the retention of 201Tl SPECT and lymph node metastasis.
Immunoglobulins are encoded by genes located in three different loci, the heavy chain (IgH), kappa light chain (Ig kappa), and lambda light chain (Ig lambda) loci. In mice, the kappa/lambda ratio of B cells is 95:5. In a previous study, we reported that kappa gene deletion causes the alternative usage of lambda 1 (93%) and lambda 2 (7%) light chains, and that the kappa anti-TNP repertoire is compensated for by the lambda repertoire even though the latter is clonally restricted in K-/- mice. To investigate the contribution of lambda antibodies to protection against virus, we compared K-/- mice with 129/Sv wild-type mice with respect to immune responses to influenza virus. PR8 virus immunized K-/- and 129/Sv mice showed no difference in the titer of anti-HA antibodies. Furthermore, the same immunized mice had sufficiently high neutralizing antibody titer to prevent infection when challenged with 7.5 x 10(4) TCID50 of PR8 virus. In addition, immunized K-/- mice were resistant to infection with 7.5 x 10(4) TCID50 and 7.5 x 10(5) TCID50 (10 and 100 LD50, respectively) of PR8 virus. Finally, K-/- mice are also capable of inducing cytotoxic T cells. These results suggest that the lambda repertoire can compensate for the kappa repertoire by generating a fully protective neutralizing antibody response.
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To evaluate the effect of percutaneous ethanol injection given alone, we studied disease recurrence and prognosis in 37 patients with solitary hepatocellular carcinoma up to 2 cm. The patients were classified as Child's class A, 22; B, 11; and C, 4. During follow-up for periods ranging from 10 to 44 (mean, 26) months, 15 of the 37 patients (40.5%) had disease recurrence. The 1-, 2-, and 3-year recurrence rates were 37, 49, and 53%, respectively (Kaplan-Meier method). Significant risk factors for recurrence included the hypervascularity and the histological differentiation of the tumor (p < 0.01). Of those 15 patients, two had local recurrence, eight had nodular recurrence (fewer than two nodules), and five had widespread multinodular recurrence. The patients with local or nodular recurrence then received repeated injections of ethanol, while those with multinodular recurrence received transarterial embolization or chemolipiodolization therapy as possible. Seven of the 37 patients died during follow-up. The 1-, 2-, and 3-year survival rates were 95, 81, and 70%, respectively (Kaplan-Meier method). No factor was significant in prognosis. We observed a significant relationship between recurrence pattern and prognosis. Patients with a widespread multinodular recurrence had a significantly shorter survival (p < 0.01). In summary, ethanol injections given alone appeared to be effective in treating small and solitary hepatocellular carcinomas. Repeated injection of ethanol of the site of recurrence was useful in prolonging survival.
AIMS: To examine the prognostic value of basement membrane expression in early stage adenocarcinoma of the lung. METHODS: Using antibodies to type IV collagen, basement membrane expression at the tumour-stromal border was immunohistochemically analysed in 30 patients with early stage adenocarcinoma of the lung (pstage I and pstage II). Two patterns of staining for type IV collagen were observed: in the first one the staining line was conserved or partially fragmented; in the second the staining line was widely fragmented or absent in more than 10% of the tumour area. The first staining pattern was categorised as continuous and the second as discontinuous. RESULTS: Of the 24 patients with pstage I adenocarcinoma, 12 (50%) cases showed a continuous pattern. In only one (16.7%) of the six patients with pstage II adenocarcinoma was this pattern evident. Five year survival was greater in pstage I adenocarcinoma (65%) than in pstage II adenocarcinoma (17%), but the difference was not significant. When the analysis was restricted to the 24 patients with pstage I adenocarcinoma, five year survival was better in continuous pattern cases (88%) than in discontinuous pattern cases (20.5%) (p < 0.05). The survival curve of 12 patients with pstage I adenocarcinoma and a discontinuous pattern resembled that of the six patients with pstage II adenocarcinoma. CONCLUSION: These findings suggest that patients with pstage I adenocarcinoma and a discontinuous pattern have histopathologically unrecognised micrometastasis when they come to surgery. The staining pattern of type IV collagen could help in the prognosis of pstage I adenocarcinoma of the lung after surgery.
To evaluate the malignancy of lung cancer, nuclear DNA content, AgNORs counts and cathepsin B activity were examined. The survival time of small cell carcinoma patients with limited disease of near diploid is longer than that with limited disease of hyperdiploid pattern. By flow cytometric technique, the proportion of DNA aneuploid pattern were higher in adenocarcinoma than in squamous cell carcinoma. In squamous cell carcinoma, the prognosis of patients with DNA aneuploid pattern was worse. However, there was no significant difference in survival time of adenocarcinoma patients. A good correlation between the AgNORs counts and tumor volume doubling time of non-small cell carcinoma of lung was observed. However, the AgNORs counts were an independent prognostic factor for survival time of patients with lung cancer. The survival time of lung cancer patients with the marked intensity of cathepsin B was significantly shorter than that of patients with negative and/or weak positive staining pattern. The AgNORs value and cathepsin B activity can serve as a pertinent marker for clinical assessment of malignancy of lung cancer.
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A patient with reactive lymphoid hyperplasia of the liver was symptom free and had no underlying disease except for diabetes mellitus. The hepatic tumor was found by ultrasound examination at routine checkup. The preoperative diagnosis of the tumor was unsuccessful despite various radiological examinations. Histological examination of the resected tumor showed that it was composed of benign-appearing lymphocytic proliferations forming lymphoid follicles that included numerous germinal centers. The germinal center was mainly composed of B-cell marker, L26-positive lymphocytes, but a few T cells were also found. Lymphocytes surrounding germinal centers were mainly T-cell marker, UCHL1-positive T-cells, and a small number of B cells. The B cells in the lymphoid follicles were stained for both kappa and lambda light chains at equal frequency, indicating polyclonal and benign nature. A diagnosis of reactive lymphoid hyperplasia of the liver seems justified.
We measured plasma levels of endothelin-1, a potent vasoconstrictor peptide, in 6 healthy controls and 20 patients with cirrhosis and correlated them with various clinical and laboratory parameters and other vasoactive substances. There was a trend toward increased endothelin-1 levels in patients with cirrhosis compared with controls (6.0 +/- 2.5 vs. 4.4 +/- 1.5 pg/ml, NS). The presence of ascites did not influence plasma endothelin-1 levels, and plasma endothelin-1 levels were not significantly correlated with serum albumin, serum bilirubin, or prothrombin time. Plasma endothelin-1 levels were significantly elevated in cirrhotic patients with esophageal varices compared with those without varices (7.5 +/- 2.5 vs. 4.5 +/- 1.6, p < 0.05). The elevation of endothelin-1 levels in patients with varices may represent a physiological compensation for the systemic vasodilation present in patients with liver cirrhosis and portal hypertension.