Studies on chemical carcinogens. XXIII. A simple method for characterization of the alkylating ability of compounds by using 4-(p-nitrobenzyl)-pyridine.
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Biomedical subjects
Publications and source records attributed to N Tamura.
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A short-term cultivation of human mammary tumors and normal mammary glands was attempted in order to establish a reproducible method for their cultivation. Epithelial cells could be cultivated consistently by the use of collagenase for tissue dissociation and the addition of insulin, human colostrum milk and cholera toxin to the culture medium. Human colostrum milk seemed to be a good additive for the growth of mammary epithelial cells but not for that of fibroblastic cells.
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The capacity of complement-mediated solubilization of immune complexes (complex releasing activity: CRA) was studied in 63 sera from eight systemic lupus erythematosus (SLE) patients. CRA in sera of active SLE (35 +/- 17.%) was significantly lower than that of inactive SLE (64.1 +/- 24.1%, P less than 0.001). In addition, 20 of 23 sera collected during active diseases demonstrated CRA values less than 50% of the control pooled serum. On the other hand, CRA of 29 of 40 sera from inactive disease exceeded the 50% level. CRA in SLE sera correlated with complement component levels and in particular with the CH50. Serial determination of CRA and of levels of circulating immune complexes (CIC), C4 and C3 in two active patients indicated that the correlation between CRA and the complement components was positive, while that between CRA and CIC was negative. These studies provide evidence that CRA may be useful for following the activity of SLE and that CRA reflects the levels of the complement components of both classical and alternative pathways. The possibility that CIC may be solubilized and opsonized by complement and cleared by the reticuloendothelial system was discussed.
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Immune precipitates were solubilized by the alternative pathway of complement assembled from isolated proteins, i.e., C3, factor B, factor D, properdin, C3b inactivator (C3bINA), and beta 1H. The kinetic curves of solubilization in the isolated system and in EGTA-serum were virtually indistinguishable. No requirement of other factors was apparent. Deletion of C3bINA and beta 1H from the complete mixture caused total consumption of C3 in the fluid phase and resulted in neither C3 binding to the complexes nor solubilization. Thus, the presence of a regulated fluid-phase reaction is essential for efficient fixation of C3 and the consequent solubilization. In addition, properdin plays an essential role in the complement-mediated solubilization in the presence of the two regulators. A large amount of C3 was incorporated into the antigen-antibody lattice. Solubilization of immune complexes started after the binding of one C3 molecule to one antibody molecule in the complexes, and the molar ratio of C3:antibody in the solubilized complexes also is approximately 1.
Experimental allergic encephalomyelitis (EAE) was induced in guinea pigs with bovine myelin basic protein (BP) with adjuvant of either synthetic muramyl dipeptide (Mdp) or Mycobacterium tuberculosis (Tbc). The following results were obtained: (1) The body temperature of the animals was studied serially after sensitization and its elevation was shown to be an early sign of EAE. (2) Several animals developed the clinical and histological signs of hyperacute EAE. (3) An optimal combined dosage of BP and adjuvant was found for induction of clinical EAE and for the the production of complement fixing (CF) antibodies. (4) Little passive hemagglutinating (PH) antibody was produced by single immunization. These results displayed no essential difference in EAE induced by either adjuvant. (5) Detectable PH antibodies developed later in addition to CF antibodies in a few animals immunized with Tbc adjuvant. These animals were skin-tested to BP, and had recovered from body weight loss or limb weakness. The results suggest that humoral antibodies play a role in modifying the disease process, even if they are not essential in production of EAE.
The reactivities of leukocytes from gastric cancer and noncancer patients to gastric tumor and normal tissue extracts were tested by the leukocyte adherence inhibition (LAI) microtest, assessing cell-mediated immunoreactivity to adenocarcinoma of the stomach. The reactivities were expressed with the LAI index. All leukocyte preparations showed low reactivities, a LAI index of less than 20%, to normal tissue extracts and only the preparations of leukocytes from cancer patients displayed high reactivities, a LAI index of more than 20%, to tumor extracts. Assuming that a patient is sensitized to gastric tumor antigen if his leukocytes respond to at least one tumor extract with a LAI index of more than 20%, approximately half of the cancer tumor antigen. Thus, the LAI microtest appears to be a simple, rapid and specific method for demonstrating cell-mediated immunity to tumor.
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New hydrophilic alkylating agents, isethionic acid esters, are proposed for use as synthetic biological alkylating agents. Methyl, ethyl, and isopropyl esters of isethionic acid were synthesized starting from isethionate and the corresponding alkyl bromides or iodides in good yields. This synthetic procedure might be generally applicable to syntheses of alkyl isethionates. The derivatives thus prepared were water-soluble, as expected, and their alkylating abilities were very similar to those of the corresponding methanesulfonates. Hence, isethinonic acid esters might be suitable for use as hydrophilic biological alkylating agents in place of methanesulfonates. In order to determine the effectiveness of isethionates as anticancer alkylating agents, 1,4-butanediol diisethionate was prepared as a model compound and its anticancer activities against adenocarcinoma 755, sarcoma 180, L1210, and P388 were compared with those of the corresponding methanesulfonate, busulfan. The isethionate was superior to busulfan in all the assay systems employed. 1,5-Pentanediol diisethionate was also prepared and assayed. The results were similar to those for the 1,4-butanediol analog. In conclusion, in the design of molecules for use as cancer chemotherapeutics, the isethionic acid ester group is worth considering, and may be preferable to other commonly used leaving groups, including methanesulfonic acid ester.
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A surgical technique is described for correcting the drooping alar rim associated with cleft lip. An incision is made on the cleft-side alar rim such that the rims will be symmetrical. After extensive undermining between the dorsal skin and alar cartilages, a suspension suture is positioned so as to pull the drooping point of the nostril rim in an anteromediocranial direction to the septovestibular junction on the normal side. The upper and lateral walls of the nasal vestibule, together with the alar cartilage, are fixed to the dorsal skin in a pushed-back position using a special technique. For the nose to retain its corrected shape, it is important that hematoma does not develop and that the chondrovestibular flap be fixed to the dorsal skin under adequate pressure and over a wide area.
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