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Primary cultures of liver cells from normal adult rats were treated with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at various concentrations for 6 days. 3'-Me-DAB treatment induced rapid proliferation of epithelial clear cells with chromosomal abnormalities and gamma-glutamyl transpeptidase (GGT) activity. In early culture, marker chromosomes were detected in 13 of 44 3'-Me-DAB-treated cultures but not in control cultures. GGT activity was not detected in the epithelial clear cells in either 3'-Me-DAB-treated or control cultures. In late culture, 21 cell lines established from 39 carcinogen-treated cultures consisted of 3 diploid cell lines, 5 pseudodiploid cell lines and 13 aneuploid cell lines. Eighteen of these 21 cell lines had marker chromosomes. Of the 2 cell lines established from 15 control cultures both were aneuploid, but a marker chromosome was detected in only one of these. GGT activity was detected in 11 of 21 cell lines established from the carcinogen-treated cultures but not in those from control cultures. Morphological features of the cell lines which varied from normal to cancerous included polymorphism, increased nuclear/cytoplasmic ratio and prominent nucleoli. No cell line established in this study developed tumors in host rats during a 1-year observation period.

A cell strain having low tumor-producing capacity was exposed in culture to 3'-methyl-N,N-dimethyl-4-aminoazobenzene (3'-Me-DAB) in the presence or absence of liver microsomes, and whether or not the cells will progress to those having high tumor-producing capacity was examined. When transplanted into rats, the cells treated with 3'-Me-DAB four (Exp-I) or thirteen times (Exp-II) formed larger tumors than untreated control cells, the latter treatment being more efficient in this regard. Furthermore, the tumors formed by the cells treated with 3'-Me-DAB in the presence of liver microsomes were considerably larger than those formed by the cells treated with 3'-Me-DAB alone. The subcutaneous tumors produced by the cells treated with 3'-Me-DAB with S-15 Mix showed poorly differentiated histology compared with those produced by control and 3'-Me-DAB-treated cells. The frequency of lung metastasis tended to increase by 3'-Me-DAB with S-15 Mix. The cells treated with 3'-Me-DAB in the presence or absence of liver microsomes differed from untreated control cells in vitro in some properties, including the size of aggregates in rotation culture, plating efficiency in liquid medium and morphology. These observations suggest that cell malignancy was promoted by 3'-Me-DAB alone as well as by 3'-Me-DAB in the presence of liver microsomes.

In order to increase the accuracy of diagnosis in lung cancer, analysis concerning cytological and histological correlation was attempted. The present study consists of 106 patients, who were seen during the past approximately five years and underwent radical surgery to remove tumors completely; mere biopsy specimens were excluded. These patients were 63 years old on the average, 78 males and 28 females, 29 cases of the hilar type (H) and 77 of the peripheral type (P), and 27 and 76 cases of the clinical stage I in H and P, respectively. Histologically, there were 53 adenocarcinomas (Ad), 38 squamous cell carcinomas (Sq), 4 adenosquamous cell carcinomas (Ad + Sq), 5 large cell carcinomas (LCC), and 6 small cell carcinomas (SCC); among them, 3 Ad and 21 Sq in H, and 50 Ad and 17 Sq in P. The overall positive percentages were 65.5 (H) and 26.0 (P) by combination of spontaneous, airsol-induced and Saccomanno's methods, against 96.6 (H) and 72.8 (P) with inclusion of brushing method. 94.8% of Sq in H and 66.7% of Ad and 70.6% of Sq in P were positive by the brushing. A comparative study of these four methods, performed at least once on the same patient, also confirmed the superiority of brushing. Cyto- and histological agreement was 21/21 (100%) for Sq in H, whereas 30/34 (88.2%) for Ad and 13/15 (86.7%) for Sq in P. In conclusion, cyto- and histological findings in H and P corresponded well, and as far as cytology of peripheral type is concerned, a combined method, especially with brushing, is strongly recommended.

Repair polymerases participating in unscheduled DNA synthesis in isolated liver nuclei, bleomycin-treated permeable cells and in ultraviolet-irradiated living cells were studied using two specific inhibitors of DNA polymerases, aphidicolin and 2', 3'-dideoxythymidine-5'-triphosphate. Unscheduled, i.e., repair, DNA synthesis in rat liver nuclei, and in bleomycin-treated permeable SR-C3H/He and XC cells was mostly attributed to DNA polymerase beta. Unscheduled DNA synthesis in human liver nuclei, bleomycin-treated permeable HeLa and HEp-2 cells, and in ultraviolet-irradiated HeLa, HEp-2 and XC cells was partially inhibited by the polymerase alpha-specific inhibitor, aphidicolin. The results suggested that both DNA polymerase alpha and beta participated in unscheduled DNA synthesis, though the respective degrees of participation differed depending on cell type and the nature and degree of DNA damage.

45Ca uptake and histamine release was examined in mast cells from rats sensitized with ovalbumin and Bordetella Bertussis as an adjuvant. The uptake of 45Ca by the mast cells was significantly increased by stimulation with ovalbumin as was the release of histamine from the mast cells. Nifedipine, a calcium antagonist, inhibited the increase in both 45Ca uptake and histamine release stimulated by ovalbumin, though the effect on 45Ca uptake was stronger than that on histamine release.

The oncogenicity of xenotropic pseudotype Kirsten murine sarcoma virus (MSV) was investigated in Sprague-Dawley rats. When fetal or newborn rats were inoculated intracerebrally with xenotropic pseudotype MSV, brain tumors developed after about one month. Tumors were induced both in the cerebrum and the cerebellum. Histologically, the tumors were predominantly glioblastoma multiforme and hemangioendotheliomas. In cerebellar lesions, malignant transformation of vascular endothelial cells, polycystic areas and numerous giant cells were noted. Proliferation of Purkinje cells was also observed in some of the cerebellar tumors. Inoculation of the same virus by other routes, such as s.c., i.p. and i.m., also caused cerebral and cerebellar tumors. Brain tumors thus induced were transplantable subcutaneously into suckling rats.

That blood transfusions aid kidney graft survival is well known. Our data show that blood transfusions, except for the red blood cell component, promote growth of transplanted tumors in mice. These clinical and experimental observations suggest that blood transfusions may induce some immunological tolerance.

A total of 252 bladder-washing and voided specimens from normal, and inflammatory and malignant lesions were examined by a direct mapping technique, i.e., a combined use of light (LM) and scanning electron microscopy (SEM). A newly-designed mesh, which consists of a piece of gelatine-covered, osmium-impregnated and polylysine-coated glass-slip with 42 compartments/25 mm2, was used in this study. This mesh permitted us to directly correlate LM and SEM images, which resulted in a shortening of the observation time. Malignancy of exfoliated urothelial cells has been determined on the basis of the presence or absence of pleomorphic microvilli as observed by SEM. Subsequently, a new "SEM grading" system for human urinary cytology was proposed. The direct mapping technique has enhanced the accuracy of the diagnosis over conventional methods, especially in cases of noninvasive, low-grade malignant tumors of the urinary bladder.

The O2- production by neutrophils was examined in 4 cases of refractory anemia with excess of blasts (RAEB) in order to evaluate the possible causes of enhanced susceptibility to infection and to gain some informations on the differentiation of neutrophils in this hematological disorder. In three of the four RAEB cases there was little O2- production by neutrophils, in addition to there being morphological anomalies of the neutrophils such as a Pelger-Huet-like anomaly, granular deficiency and binucleated cells. These results suggest that the impairment of O2- production by neutrophils in RAEB is one of the possible causes of susceptibility to infection and also suggest that the differentiation of neutrophils in this hematological disorder is faulty. The estimation of O2- production by neutrophils may be a useful diagnostic method for preleukemia.

Metastatic neuroblastoma cells in bone marrow aspirates were examined by the formaldehyde induced fluorescence histochemical method. With this method we could easily identify abnormal cells as metastatic neuroblastoma cells by observing catecholamine green colored fluorescence in their cytoplasma. This formaldehyde induced fluorescence histochemical method is significantly useful for the diagnosis of metastatic neuroblastoma of the bone marrow.

This report concerns an unusual case of adult T cell leukemia (ATL) complicated with progressive systemic sclerosis (PSS). The surface markers of peripheral blood mononuclear cells (PBM) and lymph node cells, both of which mainly consisted of leukemic cells, were examined. The effect of these cells on the pokeweed mitogen (PWM)-induced IgG synthesis by normal PBM also was studied. The leukemic cells formed rosettes with sheep red blood cells (SRBC; E) and expressed T cell antigen, Leu-1, and DR antigen. The detection of cell surface antigens was carried out by employing monoclonal antibodies against these antigens. We diagnosed this case as DR positive ATL. In terms of the immunoregulatory function of these leukemic cells, the co-culture experiments showed that these cells had some suppressive effect on the PWM-induced IgG production by allogeneic normal PBM.

We report two cases of adult T-cell leukemia in which the disease developed in a mother, aged 62 years, and her son, aged 41 years, less than four months apart. Both mother and son showed abnormal karyotypes and high titers of adult T-cell leukemia-associated antibody.

Many aspects of the etiology and pathophysiology of reversible sudden deafness remain obscure. In order to better understand the pathophysiology of reversible sudden deafness we compared the results of two therapies which have different mechanisms of action. The results of therapy with tranexamic acid alone in 49 cases (57 ears) of sudden deafness were compared with the results of treatment with so-called antisludging agents in 65 cases (69 ears) using the chi square contingency test. The same therapeutic effect was observed in both groups despite the different modes of chemical action of the two therapeutics. A series of processes involving an increase in permeability of vascular walls and related edema, and extravascular red cell oozing due to hypoxia or anoxia leading to tissue damage in the inner ear seem to be important factors in the etiology and pathophysiology of reversible sudden deafness.

Forty-one patients with small cell carcinoma of the lung were treated with a four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine. The response rate was 68% (28 responded among 41 patients), with 10 complete responses (24%) and 18 partial responses (44%). The median survival time from the initiation of chemotherapy was 11 months for patients with limited disease and 8 months for those with extensive disease. Patients who achieved complete response survived significantly longer than those who did not; the median survival time for complete responders was 14.5 months, compared to 8.5 months for partial responders and 6 months for non-responders. Myelosuppressive toxicity remained within acceptable limits, with 5% incidence of leukocytopenia (less than 1,000/microliter) and 7% incidence of thrombocytopenia (less than 50,000/microliter) following the first course of the regimen.

We applied a tumor stem cell assay using an enriched double-layered soft agar system for the detection of metastatic sites of lung cancer. Lung cancer colonies grew from 7 of 10 effusions cytologically positive for tumor cells and 7 of 10 bone marrow aspirates cytologically and histologically positive for tumor cells. Twenty-six of 29 bone marrow aspirates cytologically and histologically negative for tumor cells showed no colony growth. However, the remaining three bone marrow aspirates, which were obtained from patients with small cell lung cancer, formed colonies in soft agar. These results indicate that the tumor stem cell assay is useful for detecting metastatic sites of lung cancer.

We reported a 62-year-old man with malacoplakia of the prostate, and reviewed 49 cases of malacoplakia hitherto observed in Japan in which the lesions originated from the urogenital tract, except for one gastric case. E. Coli was emphasized as a possible causative agent for malacoplakia especially in the urogenital tract. The possible histiocytic origin of von Hansemann cells was stressed by demonstrating cytoplasmic processes and desmosomes in our prostatic case. An adjuvant use of cholinergic agents and ascorbic acid with chemotherapeutic agents was recommended for treating malacoplakia.

Glycoproteins play a significant role in neoplastic transformations. Both the levels of fucose and the activity of fucosyl transferase, which mediates the assembly of the oligosaccharide moieties of the glycoprotein chains, have been found to be elevated in neoplastic conditions. Since these elevations are common features of a variety of neoplastic cells, these two have been designated as non-specific markers of malignancy. In the present study, the fucose level and fucosyl transferase activity were determined in the sera of cancer patients and an attempt was made to establish a relationship between the two. It was found that both the fucose levels and fucosyl transferase activities showed considerable elevation in the five cancer groups studied, establishing them as useful diagnostic parameters. However, it was also observed that the rate of increased fucosyl transferase activity was not fully reflected in the resulting serum fucose levels in a few cases.

Levamisole (LMS) was given to stage III gastric cancer patients starting three days before gastrectomy, at a does of 150 mg/day for three consecutive days every other week. Survival rates of these patients were compared with those of stage III gastric cancer patients previously operated in our Department who had not received levamisole. The background factors of both groups were matched as closely as possible. Both groups were concomitantly treated with mitomycin C and FT-207. The survival rate of the LMS group was significantly higher than that of the control group when the tumor had a diameter of 4.0-8.0 cm, cancer cells infiltrated to the gastric serosa, there were metastases within the regional lymph nodes, cancer cells slightly invaded the venous capillaren and there was moderate infiltration of the stroma.

A blood recipient, aged 66, was found to have positive adult T-cell leukemia-associated antigens (ATLA), approximately half a year after a transfusion. The donor's ATLA-antibody titer was 1: 640. Routine screening of blood donors for ATLA antibody was proposed.

Electron microscopy of four human T-cell lines revealed the production of type C virus particles in two T-cell lines: one derived from acute lymphoblastic leukemia and the other from a leukemic T-lymphoid malignancy. Virus particles isolated from these cells had reverse transcriptase activity and the major internal structural protein of 30,000 daltons (p30). The indirect immunofluorescence test of these virus-producing cells with sera of patients with adult T-cell leukemia (ATL) was negative. The data indicate that these retroviruses are different from adult T-cell leukemia virus (ATLV).