Antigen-specific suppressor ("blocking") factors in tumor immunity.
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Biomedical subjects
Publications and source records attributed to K Nelson.
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Starvation and diabetes both caused a marked increase in the concentration of hepatic phosphoenolpyruvate caroboxykinase mRNA while the administration of insulin to diabetic rats or refeeding glucose to starved animals caused a marked reduction in the levels of enzyme mRNA as measured by hybridization using a cDNA probe.l The Administration of dibutyryl cAMP to a starved-refed cat caused an 8-fold induction of phosphoenolpyruvate carboxykinase mRNA in 1 h. Triamcinolone plus acidosis induced the levels of enzyme mRNA in kidney 3-fold within 6 h, however, starvation for 24h had only marginal effects. In all of the above conditions, the levels of phosphoenolpyruvate carboxykinase mRNA measured by hybridization assay agreed well with the relative levels of translatable mRNA for the enzyme. The half-time of phosphoenolpyruvate carboxykinase mRNA, determined after the administration of either alpha-amanitin or cordycepin to starved animals, was approximately 40 min. However, cycloheximide either alone or together with cordycepin, not only prevented the decrease in phosphoenolpyruvate carboxykinase mRNA sequence abundance, but induced it 2-fold. Cycloheximide itself, when injected into 21-day fetal rats in utero caused an induction of enzyme mRNA equal to that noted when dibutyryl cAMP was administered. The mRNA for phosphoenolpyruvate carboxykinase is approximately 2.8 kb in length, but nuclei from the livers of diabetic rats contain a number of putative precursor RNA species for the enzyme, up to 6.5 kb in size, all containing a poly(A) tail. Two hours after refeedng glucose to a starved rat, these nuclear RNA species could no longer be detected by hybridization to our cDNA probe.
After an outbreak of rubella in Chicago in 1978, an intensive survey of local health care personnel and hospital records identified 31 infants with congenital rubella syndrome (CRS). Rubella virus was isolated from 11 infants; rubella-IgM antibodies were demonstrated in seven infants; ten babies had persistent high rubella hemagglutination-inhibition (HI) titers. The incidence of CRS in Chicago between July 1978 and June 1979 was 48.9 per 100,000 live births. Mothers of babies with CRS frequently remembered a crash-illness during pregnancy (56%), were unmarried (74%), and were primigravidas (64%). No mother had received rubella vaccine. Review of prenatal rubella HI testing and follow-up immunization in one hospital showed that only eight (10.8%) of 74 seronegative women received rubella vaccine physicians need to place increased emphasis on detection and vaccination of susceptible adult women.
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The effects of fluocinolone acetonide (FA), retinoic acid (RA), and tosylphenylalanine chloromethyl ketone (TPCK) on two-stage promotion after 7,12-dimethylbenz[a]-anthracene (DMBA) initiation in female Sencar mice were investigated. The two-stage promotion protocol was achieved by twice weekly applications of 2 microgram of 12-O-tetradecanoylphorbol 13-acetate (TPA) for 2 weeks (stage I) followed by twice weekly applications of mezerein for 18 weeks (stage II). Separately stage I and II do not cause any tumors to develop after DMBA initiation. FA was found to be a potent inhibitor of stages I and II but to a greater degree for stage I than for stage II. RA was ineffective in stage I but was a potent inhibitor of stage II; TPCK specifically inhibited stage I but not stage II. FA and TPCK effectively counteract the appearance of the dark basal keratinocytes, whereas RA has no effect. These results provide additional evidence for the importance of dark basal keratinocytes in stage I of promotion and indicate that most of the other biochemical and morphological responses normally associated with promotion (such as polyamines) are actually associated with stage II of promotion.
Culture supernatants of spleen or thymus cells from BALB/c mice bearing transplanted, syngeneic, methylcholanthrene-induced sarcomas suppress T lymphocyte-mediated lysis of cells from the tumor borne by the donor of the spleen or thymus cells. On this basis, we hybridized thymus cells from mice bearing sarcoma MCA-1490 with cells from the T lymphoma BW5147. The hybrids (hybridomas) formed were tested for production of factors that could suppress T lymphocyte-mediated lysis of MCA-1490 cells. One hybridoma, and a clone derived from it, produced factors that suppressed the lysis of MCA-1490 cells in vitro. In addition, these factors enhanced the growth of MCA-1490 in immune mice and prevented the destruction of MCA-1490 cells by immune lymphocytes in tumor neutralization (Winn) assays. In vitro lysis of cells from another MCA-induced sarcoma by immune lymphocytes was not suppressed. The suppressor factors did not affect the proliferative response of BALB/c lymphocytes to mitogens or the generation of a cytotoxic response to C57BL/6 alloantigens. Neither did they inhibit the generation of primary or secondary cytotoxic responses to murine leukemia virus-related antigens present on a BALB/c lymphoma line, LSTRA. Although our findings suggest that these suppressor factors are specific for MCA-1490, their specificity for antigens restricted to this tumor needs further definition.
The effects of nonpromoting and weakly promoting diterpenes on skin tumor promotion by 12-O-tetradecanoylphorbol 13-acetate (TPA) were investigated. When phorbol and phorbol 12,13-diacetate (both nonpromoting) were given simultaneously with TPA after 7,12-dimethylbenz[a]-anthracene (DMBA) initiation in female mice, they had no effect on TPA promotion. However, the nonpromoter 4-O-methyl-TPA and the weak promoter mezerein were found to inhibit TPA promotion in a dose-dependent manner when given simultaneously with TPA. Because mezerein was found to be an effective inhibitor of TPA promotion when given simultaneously and because it induces many biological responses similar to those to TPA, the capacity of mezerein to act as an incomplete promoter in a two-stage promotion protocol was also investigated. Twice-weekly applications of 1,2, or 5 mug of TPA for 2 weeks after DMBA initiation produced 0, 0, and 0.5 papilloma per mouse, respectively, at 20 weeks. When the twice-weekly applications of TPA for 2 weeks were followed by twice-weekly treatments with 2 mug of mezerein for 18 weeks, the number of papillomas per mouse was 2.2, 3.5, and 9.0, respectively. Twice-weekly applications of 2 mug of TPA for 2 weeks followed by twice-weekly treatments with 1, 2, or 4 mug of mezerein for 18 weeks produced 2.1, 3.5, and 6.8 papillomas per mouse, respectively, in DMBA-treated mice. Twice-weekly doses as high as 40 mug of 4-O-methyl-TPA were not effective in producing tumors when given after a limited treatment with TPA; however, 4-O-methyl-TPA had weak activity as a first-stage promoter. The results suggest that although mezerein by itself is a weak promoter and mimics TPA in many biochemical and morphological effects it is a potent second-stage promoter in a two-stage promotion regimen.
Two patients who received pneumococcal vaccine had severe pain and swelling that extended beyond the site of injection. Both patients were atopic, and each had either received pneumococcal vaccine in the past or had had extensive laboratory contact with pneumococci. Care must be exercised in selecting patients for revaccination with pneumococcal vaccines.
A method has been developed for the assay of arylsulfatase C in tissue extracts containing arylsulfatases A and B. Significant variation of enzyme activity was observed among 26 inbred murine strains. Activity differences were apparent at all stages evaluated between 1 and 70 days postnatal age. Arylsulfatase C from representative high- and low-activity strains exhibited similar Michaelis constants, temperature optima, pH optima, thermostabilities and inhibitor profiles.
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An improvement in the extraction procedure for the quantitative determination of verapamil in human plasma is described. The advantages are: 1. the time involved in the extraction procedure is only 1/3 of that in the original method allowing the extraction of 100 samples in a working day. 2. increased mean recovery from 67% to 85% over the range of 3--90 ng verapamil/ml plasma. 3. less expenditure a) use of cheap plastic tubes instead of stoppered glass tubes. b) 1/2 the amount of heptane required as compared to the original procedure. c) use of air instead of N2 for evaporation. The lower limit of detection is 3 ng/ml which is comparable to that for the original extraction procedure. Within-batch precision over the range of 9--90 ng/ml averages 5.8% and at the lower limit of detection 17.3%. Between-batch precision over the range of 9--90 ng/ml averages 8.5% and at the lower limit of detection 19.7%. No significant difference could be found in the quantitative determination of verapamil in 27 plasma samples from patients undergoing verapamil treatment using the original and modified extraction procedures. This improvement of the extraction procedures simplifies the determination of verapamil and the only additional material required is liquid nitrogen or a suitable solvent cooled with dry ice.
Lymphoid cells specifically reactive with antigens shared by rat bowel carcinomas and mid-term embryo cells were generated by in vitro culture on monolayers of embryo cells. Spleen cells from WF females were cultured for 5 days on monolayers of syngeneic embryo cells or adult cells and assayed for cytotoxic activity on syngeneic embryo, bowel carcinoma, or adult fibroblast target cells in microcytotoxicity and 51Cr-release assays. After culture on embryo monolayers, spleen cells were cytotoxic for embryo and tumor but not for adult fibroblast target cells. Enhanced cytotoxicity was recorded when the spleen cells were cultured from females after interstrain (WF X BN) pregnancy rather than from virgin females. In contrast, previous intrastrain (WF X WF) pregnancy appeared to depress the generation of spleen cells cytotoxic for target cells bearing embryonic antigens.
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