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Monica Rodolfo Carolina Salvi Cinzia Bassi Giorgio Parmiani 《Cancer immunology, immunotherapy : CII》1990,31(1):28-36
Summary We have used a BALB/c colonic adenocarcinoma (C-26) to evaluate the therapeutic potential of recombinant interleukin-2 (rIL-2) at high and low dosages in combination with or without lymphokine-activated killers (LAK) or tumor-specific, immune lymphocytes in either an adjuvant spontaneous or an artificial metastasis system. Most (80%) of the mice that underwent s.c. C-26 tumor excision were shown to die of spontaneous metastasis with lung involvement by 1–4 months after excision. Postsurgical systemic treatment with low-dose rIL-2 (3 × 104 U/day, i.p.) increased the survival rate to 31% as compared to 21% (not significant) in excised controls while administration of high-dose rIL-2 (8 × 104 U/day) led to 53% survival (P <0.01). Both LAK cells and C-26-tumor-immune lymphocytes given during rIL-2 treatment significantly increased the effects of rIL-2 at the low but not at the high-dose, with tumor-immune effectors resulting in the highest percentage (63%) of cures. When mice bearing 3-day artificial lung metastases of C-26 cells were treated with low- or high-dose rIL-2, in combination with or without LAK or tumor-immune lymphocytes, a highly significant reduction or abrogation of the number of lung foci was observed with all treatments, including those involving or tumor-immune lymphocytes alone. Assessment of survival benefit in these mice, however, showed survival prolongation, with 20% cures achieved by low-dose rIL-2 alone and up to 65% cures by LAK in combination with low-dose rIL-2. In this system of artificial metastasis high-dose rIL-2 alone increased the survival time but failed to cure the animals, and the addition of LAK was ineffective whereas that of tumor-immune lymphocytes led to 80% cure. These results suggest that tumorimmune lymphocytes are more effective than LAK when combined with rIL-2 and that caution is necessary in extrapolating findings obtained in artificial metastasis models. 相似文献
3.
Lithium Stimulation of Membrane-Bound Phospholipase C from PC 12 Cells Exposed to Nerve Growth Factor 总被引:4,自引:4,他引:0
LiCl stimulated the formation of inositol monophosphate in PC12 cells that had been exposed to nerve growth factor (NGF) for 4-5 days. Half-maximal accumulation was observed at approximately 8 mM LiCl. Stimulation of formation of inositol bisphosphate plus inositol trisphosphate was half-maximal at approximately 1 mM LiCl. With membranes isolated from PC12 cells differentiated with NGF, the hydrolysis of added phosphatidylinositol 4,5-bisphosphate (PIP2) was stimulated by LiCl in a biphasic manner, with the first stimulation half-maximal at approximately 0.7 mM and the second half-maximal at approximately 15 mM LiCl. The apparent Km for PIP2 was lowered in the presence of 1.1 mM LiCl from approximately 200 to approximately 70 microM. Membranes from cells grown in the absence of NGF did not respond to LiCl. Although observations with intact cells are difficult to interpret without ambiguity, the results obtained with isolated membranes support our interpretation of the stimulatory action of lithium in the intact PC12 cells. 相似文献
4.
Stimulation of Inositol Incorporation into Lipids of PC 12 Cells by Nerve Growth Factor and Bradykinin 总被引:6,自引:4,他引:2
The effects of bradykinin (BK) and lithium on the phosphatidylinositol cycle were examined in PC12 cells cultured for 20 h in the presence [PC12(+)] or in the absence [PC12(-)] of nerve growth factor (NGF). BK (1 microM) induced a small stimulation of the incorporation of myo-[2-3H]inositol into the lipids of PC12(-) cells and a three- to fourfold stimulation of such incorporation into the lipids of PC12 (+) cells. About 15 h of incubation with NGF and greater than 10 min of incubation with BK were needed for maximal stimulation of inositol incorporation by BK. In the presence of 25 mM LiCl, BK stimulated the inositol monophosphate levels nine-fold in PC12 (-) and 30-fold in PC12 (+) cells. After incubation for 20 h with NGF, an increased binding of [3H]BK to the PC12 (+) cells was observed at 4 degrees C. Exposure of the cells for 30 min to 25 mM LiCl enhanced the effect of BK on the inositol incorporation into total inositol lipids, especially in PC12(+) cells. In these cells, LiCl in the presence of BK also increased several-fold the intracellular levels of inositol bisphosphate and inositol trisphosphate. 相似文献
5.
Daniela Larizza Miryam Martinetti Cinzia Pizzochero Mariaclara Cuccia Francesca Severi 《Human genetics》1992,88(4):383-387
Summary Growth failure starting before birth is a common characteristic in Turner syndrome, and its pathogenesis is still not completely explained. Experiments performed in mice and rats to test whether a genetic disparity between mothers and offspring and maternal immunological status have any influence on litter size have demonstrated that allogenic litters are significantly larger in size than genetically compatible ones. Studies in humans have given contrasting results, but some authors have found that heterozygosity at enzyme loci and in blood groups is positively correlated with intrauterine growth. HLA class I and II polymorphisms were defined in 53 patients with Turner syndrome and in their parents, and lymphocytotoxic antibody detection was performed in 36 mothers. These data were related to the patients' birth weight. The frequency of the HLA-B16 allele in patients with a birth weight > 10th centile was significantly higher in comparison with those < 10th centile. HLA antigen sharing was present in 43 couples (81.1%). Mean birth weight was 2934 ± 472 g in patients without HLA antigen parental sharing and 2721 ± 529 g in those whose parents shared HLA antigens. The mean birth weight of the 10 patients whose parents do not share HLA antigens was significantly higher than that of the patients with parental HLA–B+DR sharing (P < 0.05) and not significantly higher than in those patients with parental HLA sharing at other HLA loci. Patients whose parents shared B+DR antigens also had significantly smaller birth weights than those with B and A+B+DR sharing (P < 0.025 and P < 0.025). No significant difference in mean birth weight was found in relation to other parameters, such as mother-child histocompatibility, HLA homozygosity and lymphocytotoxic production in the mothers. 相似文献
6.
N. Lelli R. Garuti P. Pedrazzi M. Ghisellini M. L. Simone R. Tiozzo L. Cattin M. Valenti M. Rolleri S. Bertolini C. Stefanutti S. Calandra 《Human genetics》1994,93(5):538-540
During a survey of the mutations of the low density lipoprotein receptor (LDL-R) gene in Italian patients with familial hypercholesterolemia (FH), we identified a novel point mutation, that creates a new EcoRI site at the 5 end of exon 7, in a heterozygous FH subject (FH-100). The sequence of a cDNA fragment encompassing exon 7 showed the presence of a GT transversion in codon 297; this created a new EcoRI site and produced a missense mutation, leading to a Cys297Phe substitution in repeat A of the epidermal growth factor (EGF) precursor homology domain of LDL-R. Since the substitution of Cys297 disrupts the intracellular transport of the LDL-R protein, as previously demonstrated by site-directed mutagenesis, we suggest that this mutation is the cause of FH in the FH-100 proband. We screened the DNA of 303 Italian FH patients by amplification of exon 7 from genomic DNA followed by digestion with EcoRI or by Southern blotting. Two individuals (FH-64 and FH-127) were found to be carriers of the Cys297Phe mutation. Restriction fragment length polymorphism analysis demonstrated that, in two kindreds (FH-64 and FH-100), the haplotype in linkage with the Cys297Phe mutation was the same, suggesting the presence of a common ancestor. The Cys297Phe mutation has been designated FHTrieste after the name of the city in Northern Italy from which probands FH-100 and FH-127 originate. 相似文献
7.
The microsomal epoxide hydrolase (mEH)-catalyzed hydrolysis of cis-4,4′–dimethylstilbene oxide ( 1a ), cis-4,4′-diethylstilbene oxide ( 1b ), cis-4,4′-diisopropylstilbene oxide ( 1c ), and cis-4,4′-dichlorostilbene oxide ( 1d ) have been investigated using rabbit liver microsomal preparations. The kinetic parameters, Km and Vmax, and the absolute stereochemistry of the reactions have been determined and compared with those of cis-stilbene oxide ( 1e ). All epoxides 1a – d are hydrolyzed by mEH with high product enantioselectivity to give (R,R)-(+)-diols with ee ≥ 90%. The presence of the substituents on the phenyl rings markedly reduces the rates of mEH catalyzed hydrolysis with respect to cis-stilbene oxide, by increasing Km and reducing Vmax in the cases of 1a , 1b , and 1d , or reducing only the Vmax in the case of 1c . The very low Vmax, together with a persistent ability to fit into the mEH active site, make all these epoxides, and particularly 1c , inhibitors of cis-stilbene oxide hydrolysis. The kinetic and stereochemical results are interpreted on the basis of the proposed topology of the mEH active site. © 1994 Wiley-Liss, Inc. 相似文献
8.
Kohen W. Bauer N. Ryan McKenzie Cinzia Bottini Elisabetta Erba Sean A. Crowe 《Geobiology》2023,21(3):341-354
Oceanic Anoxic Events (OAEs) are conspicuous intervals in the geologic record that are associated with the deposition of organic carbon (OC)-rich marine sediment, linked to extreme biogeochemical perturbations, and characterized by widespread ocean deoxygenation. Mechanistic links between the marine biological carbon pump (BCP), redox conditions, and organic carbon burial during OAEs, however, remain poorly constrained. In this work we reconstructed the BCP in the western Tethys Ocean across OAE1a (~120 Mya) using sediment geochemistry and OC mass accumulation rates (OCAcc). We find that OCAcc were between 0.006 and 3.3 gC m−2 yr−1, with a mean value of 0.79 ± 0.78 SD gC m−2 yr−1—these rates are low and comparable to oligotrophic regions in the modern oceans. This challenges longstanding assumptions that oceanic anoxic events are intervals of strongly elevated organic carbon burial. Numerical modelling of the BCP, furthermore, reveals that such low OC fluxes are only possible with either or both low to moderate OC export fluxes from ocean surface waters, with rates similar to oligotrophic (nutrient-poor, <30 gC m−2 yr−1) and mesotrophic (moderate-nutrients, ~50–100 gC m−2 yr−1) regions in the modern ocean, and stronger than modern vertical OC attenuation. The low OC fluxes thus reflect a relatively weak BCP. Low to moderate productivity is further supported by palaeoecological and geochemical evidence and was likely maintained through nutrient limitation that developed in response to the burial and sequestration of phosphorus in association with iron minerals under ferruginous (anoxic iron-rich) ocean conditions. Without persistently high productivity, ocean deoxygenation during OAE1a was more likely driven by other physicochemical and biological factors including ocean warming, changes in marine primary producer community composition, and fundamental shifts in the efficiency of the BCP with associated effects and feedbacks. 相似文献
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10.
In situ analysis of native microbial communities in complex samples with high particulate loads 总被引:1,自引:0,他引:1
In the present study a procedure combining a cell extraction method and Fluorescence In Situ Hybridization (FISH) for molecular monitoring and quantification of bacteria in soil and aquifer samples is presented. FISH was applied to bacterial cells extracted from the matrix by density gradient centrifugation. This separation method was applied to soil and aquifer samples and produced high cell recovery of 76.5%+/-4.4 and 78.0%+/-3.2, respectively. FISH, performed on the harvested cells, permitted a perfect visualization and quantification of bacteria. This approach is therefore promising for in situ detection of indigenous bacterial communities in complex samples. 相似文献