Biomedical subjects
Publications and source records attributed to T Yano.
We present two cases of surgically proven lymphoepithelial cyst (LEC) of the pancreas that had a lipid component visualized by CT and MRI. Identification of this component in a pancreatic cystic lesion is a key to favor the diagnosis of LEC or splenic epidermoid cyst over other cystic lesions when the lesion is noted in an elderly patient.
To examine the efficacy of bleomycin on the local control of malignant pericardial effusion, we prospectively conducted a clinical trial consisting of continuous pericardial drainage and a local instillation of bleomycin. In the current study, we treated 7 patients, who suffered from malignant pericardial effusion with cardiac tamponade due to advanced-stage non-small cell carcinoma of the lung. The pericardial effusions were continuously drained through an echo-guided inserted catheter. After the effusions were drained as completely as possible, 5 mg of bleomycin were instilled locally via the catheter. In all patients but one, the draining catheter could be successfully removed. The duration of drainage ranged from 4 to 13 days (mean: 9.2 days). Five of the 7 patients achieved a complete remission of pericardial effusions, which was maintained until death or the last day of follow-up. Intrapericardial bleomycin treatment was thus found to be effective on malignant pericardial effusions without any adverse effects. However, a further study comparing the effect of pericardial instillation of bleomycin versus drainage alone would be needed for the determination of the usefulness of bleomycin.
The efficacy of the polymerase chain reaction (PCR) in the first-trimester prenatal diagnosis of Duchenne muscular dystrophy (DMD) was examined. Twenty-seven fetuses from 26 Japanese pedigrees at risk for DMD were analyzed. PCR-restriction fragment length polymorphism analysis, multiplex PCR, and dinucleotide repeat polymorphism analysis were used. Of 16 males, 11 were determined to be unaffected, 4 were affected, and the remaining 1 was undetermined. Of the 11 female fetuses, 1 was diagnosed as a noncarrier, 4 were carriers, and the carrier status of the remaining 6 was not determined at the option of the patients, although DNA polymorphisms could be detected in those patients. Prenatal diagnosis by PCR analysis was possible in 96% of the fetuses tested (26 of 27).
We describe an unusual case of B-cell neoplasm accompanied by pure red cell aplasia (PRCA) and myelofibrosis in a 67-year-old male presenting with severe anaemia. A few unclassified, myeloperoxidase-negative blastoid cells were seen on bone marrow aspiration, and erythroid cell hypoplasia and myelofibrosis on bone marrow biopsy. An autoimmune PRCA was suspected, as serum CH50, C3 and C4 levels were consistently low. Ciclosporin was effective in treating the anaemia, but anaemia returned when the drug was discontinued. Thirteen months later, the patient was admitted with pleural effusion and ascites that contained monoclonal CD19+ CD20+ immature blast cells with a complex karyotype, thought to be neoplastic B-cells. The unclassified blastoid cells seen earlier may therefore have been from the same origin. The patient deteriorated rapidly and died. Only one case of non-Hodgkin's lymphoma with PRCA and myelofibrosis has been reported previously. We discuss the possibility that dysregulated T-cells induced by neoplastic B-cells may have given rise to concomitant PRCA and myelofibrosis.
The mannose-resistant hemagglutinating factor (HAF) was extracted and purified from a diffuse adherent Escherichia coli (DAEC) strain belonging to the classic enteropathogenic E. coli (EPEC) serotype (0128). The molecular weight of HAF was estimated to be 18 KDa by SDS-PAGE and 66 KDa by Sephadex G100, suggesting that the native form of HAF consists of 3-4 monomeric HAF. Gold immunolabeling with specific HAF antiserum revealed that the HAF is not a rigid structure like fimbriae on the bacterial surface. The immunofluorescence test using purified HAF on HeLa cells, in addition to the fact that the HAF is distributed among serotypes of EPEC, suggests that HAF is a possible adhesive factor of DAEC strains.
The case of a 59-year-old man with paralytic ileus (pseudo-obstruction) associated with pheochromocytoma is reviewed. Paralytic ileus is believed to have been the result of overstimulation of alpha and beta receptors on the intestine by catecholamines. Phentolamine, bunazocin, propranolol, bethanechol and midaglizole in single administrations or in combination were administered. Phentolamine infusion clearly relieved the symptom, but ileus recurred, and the patient died of respiratory failure, liver dysfunction and disseminated intravascular coagulation syndrome. The significant role of catecholamines in causing these symptoms is discussed, and the management of this relatively rare complication is reviewed.
Effects of hyperthermia alone and combined with bromocriptine (BC) or a somatostatin analogue (SMS 201-995) were studied in vitro on normal pituitary and pituitary tumour cells (GH3 cells). GH3 cells were more sensitive to heat than normal pituitary cells and a maximal difference in survival was obtained with hyperthermia at 42.5 degrees C for 6 h. BC had cytotoxic and antiproliferative effects on GH3 cells, whereas SMS 201-995 was not effective. Hyperthermia at 42.5 degrees C for 3 h in combination with BC enhanced selective cytotoxicity for GH3 cells. In contrast, combined treatment with hyperthermia and SMS 201-995 failed to enhance cytotoxicity for GH3 cells. The combination of hyperthermia and BC could provide improved therapeutic efficacy in patients with pituitary adenomas.
The effects of the combination of cis-diamminedichloroplatinum(II) (CCDP) and hyperthermia on tumour growth were examined using transplantable human oesophageal cancer (ESO-2), having a histological type of moderately differentiated squamous cell carcinoma, in nude mice. Eighteen days after the inoculation of the tumour fragment into the subcutaneous tissue of the right hind foot, the treatment of CDDP and/or hyperthermia was performed and the antitumour effect was evaluated 21 days after the treatment. The combination of 4 mg/kg of CDDP and 43 degrees C heating for 30 min effectively depressed tumour growth in comparison with the individual treatment. The mean relative tumour weight of the combination group at 3 weeks after the treatment was 15% of that of the control group without treatment. On the other hand, pre-heating at 42 degrees C for 30 min did not influence the inhibition of tumour growth by CDDP alone or the concentration of CDDP in tumour. When pre-heating at 42 degrees C for 30 min was performed at 6 or 12 h prior to the combined treatments of 2 mg/kg of CDDP and 43 degrees C hyperthermia for 30 min, however, tumour growth depression by CDDP-hyperthermia was diminished. When pre-heating was performed 4 days prior to CDDP-hyperthermia, however, tumour growth depression occurred. These results showed that thermotolerance of tumour cells induced by pre-heating diminished hyperthermic potentiation for cytotoxicity of CDDP, though the thermotolerance did not affect the cytotoxicity of CDDP.
The study examined the effects of combination of hyperthermia (42 degrees C) and 290 MeV/u carbon-ion (C-) beams or 200 kVp X-rays on tumour regrowth delay of transplantable human esophageal cancer as an in vivo model for radiotherapy of cancer. The C-beams were more effective in the tumour growth inhibition than X-rays. The relative biological effectiveness (RBE) of C-beams against X-rays was 2.00. It was observed that the interactive hyperthermic (42 degrees C, for 30 min) enhancement of tumour regrowth delay by high-linear energy transfer (LET) C-beams was similar to that of combination of low-LET X-rays with hyperthermia. The thermal enhancement ratios (TER) were 6.10 and 5.57 for X-rays and C-beams, respectively. These results suggest that hyperthermic treatment is effective in radiotherapy not only by low-LET radiation but also by high-LET radiation such as C-beams. In conclusion, the depression of the tumour growth by the combined treatment of hyperthermia (42 degrees C) and the C-beams strongly suggests the available possible application of interdisciplinary cancer therapy for refractory tumours.
Advanced non-small cell lung cancer (NSCLC) has proven to be remarkably resistant to standard chemotherapy regimens. One potential alternative approach is the use of dose-intensive chemotherapy with supportive therapy such as granulocyte-colony stimulating factor (G-CSF). We conducted a randomized study of dose-intensive cisplatin/vindesine/mitomycin C chemotherapy (DI-PVM) and standard cisplatin/vindesine/mitomycin C chemotherapy (PVM). A total of one hundred patients with III-IV NSCLC was randomized. The DI-PVM consisted of 3 cycles of cisplatin: 80 mg/m2 (day 1), vindesine: 3 mg/m2 (days 1 and 8) and mitomycin C: 8 mg/m2 (day 1) in 3-week intervals with concurrent G-CSF. The PVM consisted of 2 cycles of the same chemotherapy in 4-week intervals. Blood cell counts were checked twice a week, and G-CSF (2 microgram/kg, SC) was administered when the count was </=2000/microliter. Eligibility criteria for this study were: no previous therapy, no active concomitant malignancy, ECOG PS </=1, age </=75 and adequate hematologic functions. The response rate for DI-PVM (26/50, 52%) was not significantly higher than that for PVM (22/50, 44%, chi2; p=0.423). However, progression-free survival for patients on DI-PVM was significantly longer than that of patients on PVM (23.7 versus 13.9 weeks, log-rank and generalized Wilcoxon test; p=0.006), as was overall median survival (57.0 versus 37.7 weeks, generalized Wilcoxon test; p=0.036). In addition, the difference in survival of patients with metastatic disease was significant (DI-PVM versus PVM; 48.9 weeks versus 23.9; p=0.032). Multivariate analysis showed that only ECOG PS was an independent prognostic variable in predicting response and survival on DI-PVM regimen. Hematological and non-hematological toxicities were equally frequent. The DI-PVM archived a longer survival than the PVM. The DI-PVM regimen should be considered a standard regimen for patients with metastatic NSCLC.
OBJECTIVE: In order to inhibit the occurrence of airborne metastasis of bronchioloalveolar cell carcinoma (BAC), we tried to activate alveolar macrophages by the inhalation of aerosolized OK-432, which is a heat and penicillin-treated lyophilized preparation of the Su strain of Streptococcus pyogenes. METHODS AND RESULTS: Alveolar macrophages were obtained from resected specimens of lung cancer patients and cultured for 24 h in the presence of various concentrations of OK-432 (0.001-1 KE/ml). The cytotoxic activity against a lung cancer cell line was augmented in a dose dependent manner and reached a plateau level at 0.1 KE/ml of OK-432. Furthermore, the alveolar macrophages produced various cytokines, i.e., IL-1, TNF-alpha, and IL-6 after 72 h cultivation with 0.1 KE/ml of OK-432. Based on the in vitro experiments, six patients with intrapulmonary metastatic BAC were therefore treated by the inhalation of aerosolized OK-432. All 6 patients inhaled aerosolized OK-432 (0.1 KE/ml) twice a day for 5 days. The inhalation therapy regimen was repeated either weekly or monthly unless the tumor markedly progressed. No adverse events were observed in any patients. Either an augmentation of antitumor cytotoxicity or TNF-alpha production by the alveolar macrophages was observed in the two of three patients examined. CONCLUSION: OK-432 inhalation therapy was found to be safe and thus warrants further investigation to determine its clinical effectiveness for BAC.
Lymph node metastasis is often the first indication of the aggressiveness of breast cancer. Effective chemotherapy in breast cancer depends on targeting the metastatic component of the disease. In order to optimize chemotherapy in the metastatic target of breast cancer, the histoculture drug response assay (HDRA) was performed on surgical specimens of primary tumor and axillary lymph node metastasis from 30 breast cancer patients. The surgical specimens were cut into approximately 10 mg pieces, and placed onto the collagen gel sponges in the medium containing previously-determined cutoff concentrations of doxorubicin (DXR), 5-fluorouracil (5-FU), cisplatin (DDP), and mitomycin C (MMC). After incubation for 7 days, the chemosensitivity of the tumor fragments was evaluated with the 3-(4,5-dimethythiazol2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) endpoint. The lymph node metastases were more resistant than the primary tumor for DXR, 5-FU, and MMC (p < 0.05) but not for CDDP. The data suggest that both primary tumor and metastases from individual patients should be tested in the HDRA to enhance clinical efficacy of chemotherapy.
The purpose of this study was to determine whether avian pathogenic Escherichia coli produced cytotoxic activity. Culture supernatants of 20 E. coli strains isolated from cellulitis lesions in chickens, five E. coli strains from avian septicemia, five from swollen head syndrome, and five from the feces of healthy chickens were incubated with primary chicken embryo fibroblast (CEF) cells, primary chicken kidney (PCK) cells, a quail fibroblast cell line (QT-35), and four mammalian cell lines (human epithelioid cervical carcinoma, African green monkey kidney, Chinese hamster ovary, and human larynx epidermoid carcinoma). Cytotoxicity was observed with supernatants from the 30 avian pathogenic strains on the two primary chicken cells (CEF and PCK). The highest dilution of culture supenatant that induced cytotoxic changes in 50% of the cells was 1/64. Supernatants from the five strains from normal feces were noncytotoxic, and none of the supernatants was cytotoxic for the QT-35 or the four mammalian cell lines. The cytotoxic effect, which was observed as early as 2 hr after exposure of the cells, was maximal at 6 hr and was evident as vacuolation, morphologically indistinguishable from that previously reported for culture supernatants of Helicobacter pylori. Like the activity in H. pylori, the cytotoxicity of the avian pathogenic strains was destroyed by heating at 70 C for 30 min and by exposure to proteolytic enzymes and was retained by filtration with a 100,000 molecular weight cut-off ultrafilter. Supernatants of two vacuolating cytotoxin-positive cultures of H. pylori failed to induce vacuolation of the CEF and PCK cells but caused the characteristic vacuolation in HeLa and Vero cells. The observations suggest that avian pathogenic E. coli produce a cytotoxin that is similar to the cytotoxin of H. pylori but may be specific for avian cells.
BACKGROUND: Altered retinoblastoma gene expression has been found in various types of cancers including non-small cell lung cancer (NSCLC) and some reports have shown it also to be associated with a poor clinical prognosis in NSCLC. MATERIALS AND METHODS: We evaluated the expression of Rb protein by immunohistochemistry in 90 patients with lung adenocarcinoma who underwent surgical resection and determined its prognostic significance. Also, the expression of p27 by immunohistochemistry and the mutations of the p53 gene by PCR-SSCP were evaluated. RESULTS: Fifty-one out of 90 tumors (56.7%) had reduced expression of the Rb gene. There were no statistical differences between the Rb expression level and clinicopathological status. There was no correlation between the Rb expression level and the p53 mutations or the p27 expression level. The 5-year survival rate in the normal group was 55.1%, which was poorer than that of 73.0% in the reduced group, but showed no statistical difference (p=0.0981). In patients with a reduced Rb-expression, the survival rate of the p53 mutation group tended to show a poorer prognosis than that of the p53 normal group (p=0.0880). In addition, the survival rate of the negative p27 expression group tended to show a poorer prognosis than that of the positive p27 expression group (p=0.0537). CONCLUSIONS: The Rb expression status was not significant as an individual factor for evaluating the prognosis in adenocarcinoma of the lung. Analyses of the accumulation of genetic alteration are necessary to identify the subset of patients with a poor prognosis.
Chemotherapy is essential in the treatment of small round cell sarcomas. However, as yet there is no progress concerning the efficacy of chemotherapy in the treatment of other types of soft tissue tumors (STS). The Histoculture Drug Response Assay (HDRA) is an in vitro chemosensitivity test that has a high correlation with clinical response, the usefulness of which has been reported in various kinds of solid tumors. However, there has never been a report on its use in STS until now. In this study, in order to investigate the variation in chemosensitivity in STS, fresh biopsy or surgical samples of STS were tested using the HDRA method. Drug sensitivity testing by HDRA showed that two drugs, ADM and THP, had a significantly higher inhibitory rate than CDDP, IFOS, or VP-16 in the thirty-three soft tissue sarcomas tested. Depending on the morphological type, spindle cell sarcomas were sensitive to THP, which showed significantly higher inhibition rates than CDDP, IFOS, or VP-16. Small round cell sarcomas were relatively sensitive to all of the drugs tested. However the drug sensitivity of pleomorphic cell sarcoma was low except for ADM and THP, while its sensitivity to THP was higher than about 70%. However, there are numerous other soft tissue sarcomas that do not belong to these categories; drug sensitivity testing in each of them and the devising of individualized treatment strategies seems necessary to improve the therapeutic outcome.
From 1973 to 1989, 110 thoracotomies for metastatic lung tumors were done on 85 patients, in our institution. The overall actuarial five-year survival rate was 31%. The five-year survival rate for carcinoma was 40% and for sarcoma was 11% (less than 0.05). A favorable outcome was obtained in the group with primary tumors of the breast, head-neck, and chorion. The outcome for patients with bone and soft tissue tumors was poor. The significant predictors of a better long-term survival for metastatic lung tumors were disease-free interval (DFI) greater than 12 months, tumor size less than or equal to 30 mm in diameter, and tumor doubling time (TDT) greater than 40 days (p less than 0.05). The number of nodules and the laterality of the sites of recurrence did not relate to survival time. Of 22 patients undergoing regional lymph node dissection, seven (32%) had positive nodes. Even in cases of a recurrent pulmonary metastasis, the three-year survival in those with multiple thoracotomies was 16%. We wish to draw attention to the finding that a prolonged survival time can be achieved for patients undergoing regional lymph node dissection or even repeated resections for a recurrent pulmonary metastases.
In this work, culture filtrates of entomopathogenic and phytopathogenic Serratia marcescens strains induced cytotoxic effects on CHO, Vero and HEp-2 cell lines. Morphological changes on sensitive cells were characterized by cell rounding and detachment as soon as 30 min of incubation, culminating in cell death after 24 h. The cytotoxic effect was completely neutralized by specific antiserum indicating that occur antigenic similarity among cytotoxins produced by these strains. The toxicity assays on plants showed that the culture supernatants did not provoke any visible morphological change and did not affect their growth. By contrast, the plants treated with bacterial suspension showed disease symptom, such as shriveling and decay of stores bulbus in onion and lettuce plantlets. In conclusion, this study show that phytopathogenic and entomopathogenic S. marcescens may produce a cytototoxin similar to that produced by clinical isolates and it is toxic to different mammalian cell lines. These results are especially important for studies involving this bacterium as biological control agent.
From 1974 to 1988, we experienced 36 benign tumors or tumor-like lesions of the lung out of 721 thoracotomies performed for the treatment of lung tumors. There were 21 hamartomas, nine inflammatory pseudotumors and six sclerosing hemangiomas. On average patients were in their fifth or sixth decade, which was somewhat younger than that for bronchogenic carcinoma. Marked female predominance was noted in the cases of sclerosing hemangioma. There were no particular characteristics with respect to symptoms or location of the tumors. Over 80% of the benign tumors were less than 30 mm in diameter. Diagnosis of the benign tumors was usually not difficult from the routine chest X-ray film. However, some cases produced shadows on X-ray films closely resembling those of lung cancer. Surgical removal preserving as much lung parenchyma as possible is indicated for definite diagnosis and treatment.