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991.
Phenotypic heterogeneity of spontaneous lymphomas of CWD mice 总被引:3,自引:0,他引:3
Animals of the inbred mouse strain, CWD, express endogenous murine leukemia viruses early in life and have a high incidence of spontaneous neoplasms. We found that approximately one half of these animals died of malignant lymphoma by the age of 16 months. Splenic enlargement was seen in all mice, but thymic involvement was unusual. One half of the CWD tumors were diffuse lymphoblastic or immunoblastic lymphomas while the remainder were large cell, small cell, or mixed cell lymphomas. Analysis of DNAs from 12 tumors for immunoglobulin and T-cell receptor gene rearrangements revealed that all six of the lymphoblastic and immunoblastic lymphomas were of T-cell origin, as was one tumor of small cleaved cells. Four of the others were clonal B-cell lymphomas and one was of uncertain lineage. Assays of a limited number of tumors for the expression of the Thy 1.2 and IgM molecules confirmed the diversity in the cellular phenotype. The results indicate that CWD mice develop primarily splenic lymphomas with an unusual degree of heterogeneity in the tumor cell phenotypes as compared with the thymic lymphomas found in other high leukemia strains. The CWD strain is a useful new model for studies of retroviral leukemogenesis and the relationship between the histopathology and immunophenotype of malignant lymphomas. 相似文献
992.
Hemoglobin biosynthesis in individual bursts in culture: studies of human umbilical cord blood 总被引:3,自引:0,他引:3
We cultured human umbilical cord blood erythropoietic precursors in methyl cellulose clonal assay and analyzed the synthetic rates of Hb A and Hb F in individual erythropoietic bursts. Hemoglobin was labeled with 14C-amino acids in culture, separated by slab gel isoelectric focusing techniques, and quantitated by fluorographic methods. Almost all bursts exhibited both Hb A and Hb F in varying ratios. Frequencies of the individual bursts differing in percentage Hb F biosynthesis had normal distributions. Natal erythropoietic precursors appeared to be randomly committed to Hb F synthesis. 相似文献
993.
REGINALD VN LORD MATTHEW G LAW ROBYN L WARD GRAHAM G GILES ROBERT JS THOMAS VICKY THURSFIELD 《Journal of gastroenterology and hepatology》1998,13(4):356-362
Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to be increasing in incidence in many countries, while the incidence of squamous cell carcinoma of the oesophagus is stable and non-cardia gastric cancers are decreasing in incidence. Age-standardized incidence rates for the years 1982–93 for oesophageal adenocarcinoma and non-adenocarcinoma, and gastric cardia and non-cardia cancers were calculated based on state cancer registry incidence data. Time trends in the age-standardized rates were assessed using linear regression. A consistent increasing trend in the incidence of oesophageal adenocarcinoma in men was seen in all states of Australia and was statistically significant in all states except South Australia. There were no consistent nationwide trends in the incidence of oesophageal adenocarcinoma in women, although a trend towards an increase in the incidence of this cancer reached statistical significance ( P < 0.05) in three states (New South Wales, Victoria, Queensland). There were no important trends in the incidence of oesophageal non-adenocarcinoma in either men or women. There were no consistent nationwide changes in the incidence of gastric cardia cancer in either men or women, although this cancer was significantly increasing in Tasmania in both men and women. The incidence of cancer of the stomach not arising at the gastric cardia was significantly decreasing in men in all states and was also decreasing in women in all states, although in women this decrease was statistically significant only in New South Wales, Victoria and Western Australia. There has been a dramatic increase in the incidence of oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in men is now approximately equal with that of non-adenocarcinoma of the oesophagus. The incidence of non-cardia stomach cancer continues to fall. 相似文献
994.
Gandrille S; Greengard JS; Alhenc-Gelas M; Juhan-Vague I; Abgrall JF; Jude B; Griffin JH; Aiach M 《Blood》1995,86(1):219-224
Because multiple risk factors in one patient may increase the clinical expression of thrombophilia, we assessed the presence in protein C- deficient patients of the factor V Arg 506 Gln mutation responsible for activated protein C resistance. Using a strategy allowing rapid screening of factor V exon 10, we studied 113 patients with protein C deficiency and 104 healthy volunteers. We detected the Arg 506 Gln mutation in 15 patients (14%) and in one healthy subject (1%). We identified a previously unpublished sequence variation leading to an Arg 485 Lys substitution in three normal subjects and seven protein C- deficient patients. A significant difference in the allelic frequency of the Arg 506 Gln factor V mutation was found between protein C- deficient patients heterozygous for an identified protein C mutation (n = 84; allelic frequency, 4.8%) and protein C-deficient patients with no identified mutation in the protein C gene coding regions (n = 25; allelic frequency, 14%). The results demonstrate that a significant subset of thrombophilic patients has multiple genetic risk factors although additional secondary genetic risk factors remain to be identified for the majority of symptomatic protein C-deficient patients. 相似文献
995.
Hereditary pyropoikilocytosis (HPP) is a recessively inherited hemolytic anemia characterized by severe poikilocytosis and red blood cell fragmentation. HPP red blood cells are partially deficient in spectrin and contain a mutant alpha or beta-spectrin that is defective in terms of spectrin self-association. Although the nature of the latter defect has been studied in considerable detail and many mutations of alpha-spectrin and beta spectrin have been identified, the molecular basis of spectrin deficiency is unknown. Here we report two mechanisms underlying spectrin deficiency in HPP. The first mechanism involves a thalassemia-like defect characterized by a reduced synthesis of alpha-spectrin as shown by studies involving synthesis of spectrin in two unrelated HPP probands and their parents: One parent carries the elliptocytogenic spectrin mutation, whereas the other parent is fully asymptomatic. Peripheral blood mononuclear cells as a source of erythroid burst-forming unit (BFUe) were cultured in a two-phase liquid culture system that gives rise to terminally differentiated erythroblasts. Pulse-labeling studies of an equal number of erythroblasts or morphologically identical maturity showed that the synthesis of alpha-spectrin as well as the mRNA levels as measured by the competitive polymerase chain reaction (PCR) method are markedly reduced in the presumed asymptomatic carriers and the HPP probands. In contrast, the synthesis and mRNA levels of beta-spectrin were normal. These results constitute a direct demonstration of an alpha-spectrin synthetic defect in a subset of asymptomatic carriers of HPP and HPP probands. The second mechanism underlying spectrin deficiency involves increased degradation of mutant spectrin before its assembly on the membrane. This is evidenced by pulse labeling studies of erythroblasts from a patient with HPP associated with a homozygous state for spectrin alpha I/46 mutation (leu-pro mutation at AA 207 of alpha-spectrin). These studies showed that although spectrin is synthesized in the cytosol in normal amounts, the rate of turnover of alpha-spectrin is faster resulting in about 40% to 50% reduced assembly of alpha-spectrin and beta-spectrin on the membrane. Thus, spectrin deficiency in this case is at least in part caused by increased susceptibility of the mutant spectrin to degradation before its assembly on the membrane. We conclude that at least two separate mechanisms underlie the molecular basis of spectrin deficiency in HPP. 相似文献
996.
Antiphospholipid antibodies and venous thromboembolism 总被引:14,自引:2,他引:14
Ginsberg JS; Wells PS; Brill-Edwards P; Donovan D; Moffatt K; Johnston M; Stevens P; Hirsh J 《Blood》1995,86(10):3685-3691
The clinical relevance of antiphospholipid antibodies (APLA) in patients without systemic lupus erythematosus who have venous thromboembolism (VTE) in unknown. Limited evidence suggests that there is an association between the presence of APLA and both initial and recurrent episodes of VTE and that patients with APLA and VTE are resistant to warfarin therapy. Unselected patients with a first episode of clinically suspected deep vein thrombosis or pulmonary embolism were evaluated with objective tests for VTE and with laboratory tests for APLA; the latter included tests for the lupus anticoagulant (LA) and anticardiolipin antibodies (ACLA). Patients with VTE were treated with anticoagulant therapy and observed during and after discontinuation of anticoagulants for symptomatic recurrence of VTE. There was a strong association between LA and VTE (odds ratio, 9.4; 95% confidence interval [CI], 2.1 to 46.2) and 9 to 65 (14%; 95% CI, 7% to 25%) patients with VTE had LA. There was no association between the presence of ACLA and VTE (odds ratio, 0.7; 95%CI, 0.3 to 1.7) because of the high frequency of positive ACLA assays in patients without VTE. None of the 16 patients with VTE and APLA developed recurrent VTE while receiving warfarin therapy. There was no difference in rates of recurrent VTE in patients with or without APLA after anticoagulant therapy was discontinued. The strong association between LA and VTE suggests that testing for LA in patients with VTE is useful. The measurement of ACLA in patients with VTE has no clinical usefulness because the results are abnormal in a high proportion of patients without VTE. Although the presence of APLA in patients with VTE was not associated with resistance to a conventional intensity of warfarin or an increased risk of recurrent VTE after discontinuation of warfarin, a larger study should address these issues in a subgroup of patients with VTE and LA. 相似文献
997.
998.
Kitchen L; Leal M; Wichmann I; Lissen E; Ollero M; Allan JS; McLane MF; Essex M 《Blood》1985,66(6):1473-1475
We tested serum samples from 50 hemophiliacs from Sevilla, Spain, for antibody to HTLV-III by indirect membrane immunofluorescence (IMI) and radioimmunoprecipitation with SDS polyacrylamide gel electrophoresis (RIP-SDS/PAGE). All had received commercial clotting factors from the United States with the exception of one hemophiliac who had never been transfused. Thirty-four (68%) reacted with HTLV-III-infected cells (H9/HTLV-III) by both methods, but not with the uninfected line (H9). Of 41 hemophilia-A patients tested, 28 (68%) were positive, and of nine hemophilia-B patients, six (66%) were positive. The nontransfused hemophilia-B patient was negative for antibody to HTLV-III by both methods. One patient with clinical AIDS tested positive as did six of seven with chronic unexplained lymphadenopathy. The eight individuals with AIDS or lymphadenopathy all had hemophilia A. We conclude that exposure to HTLV-III is widespread among asymptomatic hemophiliacs in Spain. 相似文献
999.
Serological confirmation of human T-lymphotropic virus type I infection in healthy blood and plasma donors 总被引:10,自引:0,他引:10
Anderson DW; Epstein JS; Lee TH; Lairmore MD; Saxinger C; Kalyanaraman VS; Slamon D; Parks W; Poiesz BJ; Pierik LT 《Blood》1989,74(7):2585-2591
We wished to develop criteria for serological confirmation of human T- lymphotropic virus type I (HTLV-I) infection in healthy donors. Selected serum or plasma samples reactive by HTLV-I enzyme immunosorbent assay or gel-agglutination assays with at least one viral- specific band on Western immunoblot (WIB) were tested in six laboratories by four WIBs and four radioimmunoprecipitation assays (RIPAs) for antibodies to HTLV-I proteins encoded by gag (p19 and p24), env (gp46 and/or gp61), and tax (p40x) genes. One hundred forty-two donor sera were obtained from 38 Japanese, 69 American, and 35 Caribbean blood or plasma donors. Among these samples, WIB assays appeared more sensitive to p24 antibodies, whereas RIPAs were significantly more sensitive to gp61 antibodies. All sera (137) with gp61 antibodies had p24 antibodies. Of the 137 sera positive for p24 and gp61 antibodies, p19 antibodies were detected in 129 sera, and p40x antibodies were detected in 108. In sera with p19 antibodies and antibodies to env- or tax-encoded proteins, p24 antibodies were always present. Antibodies to p40x were not found in the absence of gp61 antibodies. Virological evidence of infection was found in seven American donors by lymphocyte coculture (one HTLV-I, one HTLV-II) or by polymerase chain reaction (three HTLV-I, two HTLV-II). Sera from all seven donors showed p24 and gp46 and/or gp61 antibodies. We suggest that seroreactivity to both p24 and gp46 and/or gp61 by WIB or RIPA or both are suitable criteria to confirm but not to distinguish HTLV-I and HTLV-II infections. 相似文献
1000.
Expression of embryonic zeta-globin and epsilon-globin chains in a 10- year-old girl with congenital anemia 总被引:1,自引:0,他引:1
A 10-year-old Danish girl with congenital anemia is described. At birth, she had severe anemia and erythroblastosis and was transfused a number of times during the first year. The need for transfusions has since declined steadily. Her reticulocyte counts varied between 2% and 15%, and her bone marrow aspirate showed some dyserythropoietic features. Her hemoglobin F level was consistently elevated, up to as much as 41%. Her erythrocytes had a normal level of I antigen but an undetectable level of i antigen. Moreover, embryonic zeta-globin and epsilon-globin chains were present in some of her circulating erythrocytes. These findings may represent the manifestations of a new variant of congenital anemia. 相似文献