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11.
12.
Debelenko LV; Brambilla E; Agarwal SK; Swalwell JI; Kester MB; Lubensky IA; Zhuang Z; Guru SC; Manickam P; Olufemi SE; Chandrasekharappa SC; Crabtree JS; Kim YS; Heppner C; Burns AL; Spiegel AM; Marx SJ; Liotta LA; Collins FS; Travis WD; Emmert-Buck MR 《Human molecular genetics》1997,6(13):2285-2290
Lung carcinoids occur sporadically and rarely in association with multiple
endocrine neoplasia type 1 (MEN1). There are no well defined genetic
abnormalities known to occur in these tumors. We studied 11 sporadic lung
carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene
on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy
fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was
studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene
were inactivated. All four tumors showed the presence of a MEN1 gene
mutation and loss of the other allele. Observed mutations included a 1 bp
insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide
substitution affecting a donor splice site. Each mutation predicts
truncation or potentially complete loss of menin. The remaining seven
tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH.
The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a
complex germline MEN1 gene mutation. The data implicate the MEN1 gene in
the pathogenesis of sporadic lung carcinoids, representing the first
defined genetic alteration in these tumors.
相似文献
13.
Postnatal development of cyclooxygenase-2 in the rat kidney 总被引:2,自引:0,他引:2
Prostaglandins are local mediators/modulators of kinin effects in the kidney. The prostaglandin G2/H2 synthase (cyclooxygenase, COX) is the key regulatory enzyme of prostanoid synthesis pathway. Two COX isoenzymes (constitutive or COX-1 and inducible or COX-2) have been described in the rat kidney. We have demonstrated the presence of COX-2 in a subset of thick ascending limb of Henle (TAL) cells in normal adult rats [Vio, C.P., Cespedes, C., Gallardo, P., Masferrer, J.L., 1997. Renal identification of cyclooxygenase-2 in a subset of thick ascending limb cells. Hypertension 30, 687-692]. The present work was designed to evaluate COX-2 during the postnatal development of the rat kidney. Kidneys from Sprague-Dawley rats were studied during postnatal days 5, 10, 15 days and adult (60 days) (n = 8 each group). Renal tissue was immunostained with specific antibodies against COX-2. COX-2 was observed exclusively in TAL. A small number of COX-2 cells were observed during early postnatal life, increasing from day 5 to 15, and decreasing thereafter to reach adult levels. During maximal expression, near 20% of TAL were COX-2 positive whereas in early postnatal period and adults, only 2% of TAL cells contain COX-2. This transient induction of COX-2 during development suggest that the enzyme is necessary for the postnatal development of the kidney. This change in COX-2 seems to correspond to a derepression of COX-2 gene expression secondary to low levels of glucocorticoids. 相似文献
14.
A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma 总被引:8,自引:2,他引:8
Chen J; Giovannucci E; Hankinson SE; Ma J; Willett WC; Spiegelman D; Kelsey KT; Hunter DJ 《Carcinogenesis》1998,19(12):2129-2132
We examined the relationship between a functional polymorphism (667C--
>T, ala-->val) of the methylenetetrahydrofolate reductase gene
(MTHFR) and the risk of colorectal adenomas in the prospective Nurses'
Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR
val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval
(CI) 0.84-2.17] was not significantly associated with risk of adenomas.
This lack of association was observed for both small (RR = 1.36, 95% CI
0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore,
there was no significant interaction between this polymorphism and
consumption of either folate, methionine or alcohol. We also examined the
relationship of a newly identified polymorphism (asp919gly) of the
methionine synthase gene (MS) with the risk of colorectal adenomas in the
same population. The MS gly/gly polymorphism was also not significantly
associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70).
These results, which need to be confirmed in other studies, suggest that
the MTHFR val/val polymorphism, which has been previously inversely
associated with risk of colorectal cancer, plays a role only in a late
stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may
protect against malignant transformation in the subset of benign adenomas,
which may progress to malignancy.
相似文献
15.
16.
Transforming growth factor beta (TGF-beta) is a bifunctional regulator of the growth of myeloid progenitors and is here demonstrated to directly inhibit the growth of primitive erythroid progenitors by 95% to 100% regardless of the cytokines stimulating growth. Autocrine TGF- beta production of primitive hematopoietic progenitors has previously been reported. In the present study, a neutralizing TGF-beta antibody (anti-TGF-beta) added to serum-containing cultures, resulted in a 3-, 4- , and 25-fold increase in burst-forming unit erythroid (BFU-E) colony formation in response to interleukin-4 (IL-4) plus erythropoietin (Epo), SCF plus Epo, and IL-11 plus Epo, respectively. The growth of BFU-E progenitors has been suggested to require a burst-promoting activity in addition to Epo. Accordingly, we observed no BFU-E colony formation in serum-containing cultures in response to Epo alone. In contrast, 50 BFU-E colonies were formed when anti-TGF-beta was included in the culture. In serum-free cultures, Epo also stimulated BFU-E colony formation in the absence of other cytokines, whereas anti-TGF- beta had no effect on the number of colonies formed. Quantitation of TGF-beta 1 in serum by an enzyme-linked immunosorbent assay method showed predominantly the presence of precursor (latent) TGF-beta 1, but also showed active TGF-beta 1 at a concentration sufficient to potently inhibit erythroid colony formation. Thus, neutralization of active TGF- beta 1 in serum shows that Epo alone is sufficient to stimulate the growth of murine BFU-E progenitors. 相似文献
17.
Fluorescent in vivo tracking of hematopoietic cells. Part I. Technical considerations 总被引:3,自引:1,他引:3
We report a new technology for in vivo tracking of hematopoietic cells, using fluorescent lipophilic probes. Because the probe is irreversibly bound in the lipids of the cell membrane; substantial numbers of dye molecules can be incorporated per cell and thus substantial signal to noise can be achieved. Although this technology can be used for all hematopoietic cells, these first findings are reported on red blood cells (RBCs) owing to the importance of the membrane to RBC function and integrity. We demonstrated that labeling 10% of the RBCs of a rabbit and reinjecting them into the animal makes possible the tracking of these cells at various times after injection. Furthermore, the labeling appears not to affect in vivo cell lifetime or cellular volume changes in response to hypotonic shock. The single cell fluorescence intensity of the labeled RBCs remains relatively constant for 60 days, and an immune response appears not to be generated against labeled cells. That labeled RBCs have lifetime kinetics in vivo, as shown in other studies, indicates that the membranes are functioning normally and are unaltered by the labeling technology. The technology we present is also applicable to white blood cells, bone marrow, and platelets. 相似文献
18.
Design,Synthesis, Biological Evaluation and Binding Mode Modeling of Benzimidazole Derivatives Targeting the Cannabinoid Receptor Type 1
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19.
Dittrich R Recabarren S Mitze M Jaeger W 《Journal of cancer research and clinical oncology》2001,127(8):495-501
Purpose: In this study the effect of continuous stimulation of gonadotropins on sex cord stromal tumors in the rat was examined. Methods: Sex cord stromal tumors were induced by transplantation of ovaries under the splenic capsule of ovariectomized rats. Beginning
180 days after transplantation, these tumors were taken out and cut into several pieces, which were then retransplanted (by
isotransplantation) under the splenic capsule of 80 either intact or ovariectomized rats. Results: Most of the tumor grafts grew up to a median size of 0.7 cm in ovariectomized rats. However, some of the tumors recovered
from recipient rats that were retransplanted with donor tumors differed significantly from the others. Characterized by a
high mitotic rate, nuclear atypia, size (up to 3.8 cm) as well as growth in intact animals, these tumors were defined as malignant.
They could be kept in culture and always led to the development of metastases after retransplantation into other rats. Conclusion: Benign sex cord stromal tumors can show malignant growth after transplantation. This study for the first time demonstrates
that gonadotropins are involved in the induction of ovarian malignancies.
Received: 15 December 2000 / Accepted: 15 February 2001 相似文献
20.
Cultured adherent human macrophages and a promonocytic cell line, U 937, were previously shown to produce a Mr 95,000 gelatin-binding protein. The protein has no immunologic cross-reactivity with the well- characterized gelatin-binding protein fibronectin and the Mr 70,000 gelatin-binding protein produced by a variety of mesenchymal or epithelial cell types (T. Vartio et al, J Biol Chem 257:8862, 1982). In the present study the Mr 95,000 protein was found in Triton X-100 extracts of granulocytes purified from human blood buffy coat. The protein, as isolated by gelatin-agarose, was immunologically cross- reactive with the corresponding macrophage protein in immunoblotting assay. When peripheral blood and bone marrow cells were examined for the presence of the Mr 95,000 protein by indirect immunofluorescence, positive staining was detected only in differentiated granulocytes but not to any significant extent in metamyelocytes, myelocytes, promyelocytes, or in normal or leukemic blasts. In granulocytes the protein had a granular cytoplasmic distribution. In freshly prepared monocyte cultures, the Mr 95,000 protein was detected in low amounts in the cytoplasm, while along with differentiation of the cells into macrophages, the immunofluorescence increased in a reticular and vesicular cytoplasmic pattern and in a juxtanuclear cap, probably representing the Golgi complex. In conclusion, the Mr 95,000 gelatin- binding protein was specifically detected in macrophages and granulocytes and may thus serve as a differentiation marker for these phagocytic cells. 相似文献