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51.
Bone marrow transplantation (BMT) is often followed by significant morbidity and mortality due to protracted immunodeficiency. We have hypothesized that the bone marrow-ablative regimen may delay the recovery of normal immune function following transplantation by impairing the interaction of host endothelial cells with circulating graft-derived lymphocytes. This report compares the relative effects of busulfan (an alkylating drug) and gamma-irradiation on the tissue- specific localization potential of lymphocytes and the eventual recovery of immune function within syngeneic murine transplant recipients. Localization of normal lymphocytes into peripheral lymph nodes of irradiated BMT recipients was markedly less (less than 50%) than in busulfan-treated or normal mice over the first 2 months post- BMT. This finding correlated with irradiation-induced endothelial cell edema and microvascular occlusions within lymphocyte-receptive areas of the nodal microvasculature. The effect of both preparative regimens on the recovery of contact hypersensitivity (CHS) was also analyzed. This response recovered more quickly (between 1 and 2 months) in busulfan- pretreated animals. Further experiments demonstrated that the decrease in CHS responsiveness appeared, in part, related to a depression in the capacity of lymphocytes to localize into skin sites of antigen deposition within irradiated mice. The impairment of tissue-specific lymphocyte localization may represent a novel mechanism by which whole body irradiation can contribute to delayed immunologic reconstitution following bone marrow transplantation. 相似文献
52.
G Lesage SS Glaser S Gubba WE Robertson JL Phinizy J Lasater RE Rodgers G Alpini 《Gastroenterology》1996,111(6):1633-1644
BACKGROUND & AIMS: After partial hepatectomy, liver regeneration occurs with the return of hepatocyte mass to normal, Limited data exist regarding the renewal of the biliary tree after partial hepatectomy. This study tested the hypothesis that, after partial hepatectomy, the biliary tree regenerates by proliferation of the remaining cholangiocytes, leading to an increase in secretin-induced ductal bile secretion. METHODS: After 70% partial hepatectomy, cholangiocyte proliferation was assessed in situ by morphometric analysis and In vitro by measurement of 3H-thymidine incorporation. Ductal secretion was estimated by measurement of secretin receptor gene expression and adenosine 3',5'-cyclic monophosphate (cAMP) levels in vitro and by the effect of secretin on ductal bile secretion in vivo. RESULTS: DNA synthesis was undetectable in control cholangiocytes, increased and peaked at day 3 after partial hepatectomy, and returned to normal by day 28. Morphometric analysis showed regrowth of the biliary tree beginning at day 1 with restoration by day 10. The expression of secretin receptor gene and secretin-induced cAMP levels and secretin- induced bicarbonate-rich choleresis increased during the period of bile duct renewal. CONCLUSIONS: After partial hepatectomy, the increase in secretin-induced ductal bile secretion observed during bile duct renewal results from proliferation of remaining cholangiocytes. (Gastroenterology 1996 Dec;111(6):1633-44) 相似文献
53.
54.
Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro 总被引:3,自引:0,他引:3
Kelton JG; Meltzer D; Moore J; Giles AR; Wilson WE; Barr R; Hirsh J; Neame PB; Powers PJ; Walker I; Bianchi F; Carter CJ 《Blood》1981,58(3):524-529
Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia. 相似文献
55.
Interleukin-8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long-term myelolymphoid repopulating ability 总被引:10,自引:5,他引:10
Interleukin-8 (IL-8) belongs to a family of chemoattractant cytokines involved in chemotaxis and activation of neutrophils. As in vivo administration of IL-8 induces granulocytosis and the release of immature white blood cells into the circulation, we assessed a possible mobilizing effect of IL-8 on myeloid progenitor cells. IL-8 was administered at intraperitoneal doses ranging from 0.1 to 100 micrograms per mouse to female Balb/C mice (aged 8 to 12 weeks; weight, 20 to 25 g). Animals were killed at time intervals ranging from 1 to 240 minutes after IL-8 administration, and blood, bone marrow, and spleen cells were harvested. Injection of 30 micrograms IL-8 resulted in an increment from 25 +/- 9 to 418 +/- 299 granulocyte-macrophage colony-forming units (CFU-GM) per milliliter blood at 15 minutes after a single intraperitoneal injection. Sixty minutes after the injection of IL-8, the numbers of circulating CFU-GM per milliliter blood had almost returned to pretreatment values (82 +/- 39 CFU-GM per milliliter). A dose of 100 micrograms IL-8 per animal did not result in a further increment in the number of circulating CFU-GM. Transplantation of 5 x 10(5) blood-derived mononuclear cells (MNC) obtained at 30 minutes after IL-8 injection (30 micrograms) resulted in 69% survival of lethally irradiated (8.5 Gy) recipients at 60 days versus 22% for animals transplanted with an equal number of nonprimed blood-derived MNC. Transplantation of 1.5 x 10(6) MNC obtained from IL- 8-treated donors resulted in 100% survival. Six months after transplantation, female recipients of MNC derived from IL-8-treated male donors were killed, and chimerism was determined in bone marrow, spleen, and thymus using a Y chromosome-specific probe and fluorescent in situ hybridization (FISH). The majority of bone marrow, spleen, and thymus cells (83% +/- 25%, 89% +/- 5%, and 64 +/- 28%, respectively) consisted of Y chromosome-positive cells, showing that the IL-8- mobilized cells had myelolymphoid repopulating ability. We conclude that IL-8 is a cytokine that induces rapid mobilization of progenitor cells and pluripotent stem cells that are able to rescue lethally irradiated mice and that are able to completely and permanently repopulate host hematopoietic tissues. 相似文献
56.
Hereditary elliptocytosis (HE) is a heterogeneous disorder of red blood cells frequently associated with abnormal limited tryptic digestion of the alpha I domain of spectrin and impaired spectrin dimer self- association. We studied two related individuals with poikilocytic hereditary elliptocytosis (HE) of different severity. Limited tryptic digestion of spectrin from these individuals showed the presence of a variant alpha I/50b Kd peptide at the expense of the normal alpha I/80 Kd peptide. Amino acid sequence analysis of the abnormal peptide showed that the proteolytic cleavage occurred after the arginine at position 470 of the alpha spectrin chain. Spectrin from these patients had an impaired ability to undergo self-association, as evidenced by increased amounts of spectrin dimers in 4 degrees C extracts of erythrocyte membrane from affected individuals. The polymerase chain reaction was used to study the DNA sequence of the alpha spectrin gene encoding the region of the alpha spectrin chain surrounding the abnormal proteolytic cleavage site. We detected the in-frame deletion of the trinucleotide CAT, encoding histidine 469, two amino acid residues to the N-terminal side of the abnormal proteolytic cleavage site between residues 470 and 471. Similar to many other defects of spectrin associated with HE, this deletion occurs in helix three of repeat 5 of the proposed triple helical model of spectrin repeats. 相似文献
57.
Kroef MJ; Fibbe WE; Mout R; Jansen RP; Haak HL; Wessels JW; Van Kamp H; Willemze R; Landegent JE 《Blood》1993,81(7):1849-1854
Interstitial deletions of the long arm of chromosome 5 are among the most characteristic abnormalities observed in myeloid disorders. To assess the lineage involvement of peripheral blood cells from patients with a 5q--anomaly, purified neutrophils, monocytes, T lymphocytes, and B lymphocytes were analyzed for loss of heterozygosity using six different highly polymorphic mininucleotide and dinucleotide (CA) repeat sequences from the 5q31 to 5q33 region. Ten patients were screened by polymerase chain reaction (PCR) amplification and proved to be informative for at least one marker. Six patients showed a complete or partial disappearance of an allele in myeloid cells, whereas cells of lymphoid lineages exhibited full heterozygosity. The other patients displayed no allelic loss, indicating that the informative markers were located outside the deleted chromosomal segments. In addition, three female patients who were also polymorphic for the BstXI site in the PGK- 1 gene were analyzed for the methylation status of this gene. Clonality of hematopoiesis, as determined by non-random X-chromosome inactivation, followed the same cell pattern as the 5q-specific allelic losses. In conclusion, using tumor-specific and clonal markers, we have demonstrated that the 5q- anomaly is restricted to cells of myeloid origin, leaving lymphoid cells unaffected. 相似文献
58.
59.
M Bestak D R Miller J S Mouradian 《American journal of diseases of children (1960)》1979,133(8):831-833
A 4-year-old boy with multiple café-au-lait spots and a family history of neurofibromatosis had generalized edema, histiocytic rash characterized by benign histiocytic infiltration, hepatomegaly, and life-threatening infection. Six months later, progessive splenomegaly led to juvenile chronic myelocytic leukemia that eventually proved fata. The case represents an important association of diseases. 相似文献
60.
目的:观察非穿透性小梁切除术联合人羊膜植入的临床效果。方法:对18例(30眼)中、晚期开角型青光眼进行非穿透性小梁切除术联合人羊膜植入,术后观察视力、视野、眼压及滤过泡形成情况。结果:术后随访3-9月,视力、视野稳定,眼压≤20mmHg(1mmHg=0.133kPa),滤过泡形成良好,并发症少。结论:非穿透性小梁切除术 联合人羊膜植入治疗开角型青光眼,能有效降低眼压,形成功能性滤过泡和并发症少等优点,是治疗开角型青光眼较理想的方法。 相似文献