摘要:

AbstractIn a patient diagnosed with histiocytic medullary reticulosis (HM), we examined immunocytes for their responsiveness towards known signaling molecules. Both the granulocytes and monocytes were found to exhibit a high level of spontaneous activation (96% compared to normal cells 7%;P<0.001). These cells could not be downregulated when exposed to morphine. Following patient treatment with doxorubicin and cyclophosphamide, the immunocytes still exhibited a high spontaneous activation. They responded to morphine exposure in vitro with a cell rounding and becoming immobile for only 20 min whereas normal cells would remain round and immobile for up to 1–2 h. An examination of the plasma from the HM patient revealed that monocyte colony stimulating factor (MCSF) levels were elevated (6.4 and 5.78 compared to a control range of 1–1.75 ng/ml). In the HM patient, the immunocytes did not express the opiate selective and opioid peptide insensitive receptor, μ3, supporting the lack of opiate action. Given this finding, we incubated normal monocytes with MCSF and found that it significantly reduced the μ3 Bmax. Given the role of intracellular calcium in the activation process of immunocytes, we examined the action of various calcium channel blockers for their ability to inhibit the activated HM monocytes. The agents (nimodipine, cardiazem, and verapamil; 10−9M) were able to inhibit the HM‐associated chemokinesis. Taken together, the data indicate that in the HM patient the immunocytes appear to be overactivated because stimulatory molecules are high and have the ability to downregulate the normal “braking” process. Additionally, the data indicate that MCSF deregulation may be involved as an initiating factor for this disorder. Am. J. Hematol. 56:197–205, 1997. © 1997

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<197::AID-AJH1>3.0.CO;2-S

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractTwenty‐seven lymphomas of mucosa‐associated lymphoid tissue (MALT) derived from distinct anatomical sites were tested for the presence of genetic lesions commonly involved in B‐cell lymphomagenesis, including activation of proto‐oncogenes (BCL‐1,BCL‐2,BCL‐6, and c‐MYC), disruption of tumor suppressor loci (p53, 6q), and infection by viruses [Epstein‐Barr virus (EBV), and Kaposi's sarcoma‐herpesvirus/human herpesvirus‐8 (KSHV/HHV‐8)]. Sixteen low‐grade and 11 high‐grade MALT‐lymphomas were included in the study. The presence of genetic lesions was tested by a combination of molecular approaches, including Southern blot hybridization, polymerase chain reaction (PCR), and PCR‐single strand conformation polymorphism followed by DNA direct sequencing. Alterations ofBCL‐1,BCL‐2, or c‐MYC, as well as infection by KSHV/HHV‐8, scored negative in all MALT‐lymphomas analysed. Conversely, rearrangements ofBCL‐6 and mutations ofp53clustered with a fraction of high‐grade MALT‐lymphomas. Deletions of 6q occurred in selected cases of both low‐ and high‐grade MALT‐lymphomas, whereas a monoclonal infection by EBV was restricted to one single patient. These data corroborate the notion that the molecular pathogenesis of MALT‐lymphomas differs substantially from that of nodal B‐cell lymphomas. Occasionally, however, a proportion of high‐grade MALT‐lymphomas may harbor selected genetic lesions among the ones commonly involved in nodal B‐cell lymphomage

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<206::AID-AJH2>3.0.CO;2-0

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractMitoxantrone (M) is a synthetic aminoanthraquinone with anti‐leukemic activity in patients with daunorubicin (D) resistant acute leukemia. The Cancer and Leukemia Group B (CALGB) has undertaken a limited access pilot study in which M, 12 mg/m2, over 30 min, daily for 3 days, and cytosine arabinoside (Ara‐C), 100 mg/m2/day by constant infusion for 7 days were used for the induction of newly diagnosed patients with AML. Responding patients were consolidated with daunorubicin, 45 mg/m2/day for 3 days, and 7 days of Ara‐C. After a second consolidation identical to induction, no further therapy was given. Twenty‐nine patients with a median age of 50 years (range 18–72) were entered in the study; 18 were males and 11 females. Twenty‐four (83%) patients achieved CR, 1 patient achieved a PR, and 4 died in induction from leukemia‐related causes. Two patients died in CR from consolidation‐related neutropenic sepsis and two additional patients died in CR. Of 24 patients, 7 remain disease‐free at a median follow‐up interval of 8 years. The regimen is active and well tolerated. The duration of disease‐free survival in responding patients is consistent with that seen in similar regimens using intensification chemotherapy without prolonged maintenance. Am. J. Hematol. 56:214–218, 1997.

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<214::AID-AJH3>3.0.CO;2-#

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractA unique case with diffuse mixed malignant lymphoma was investigated for gene rearrangement on the level of T‐cell receptor (TCR), heavy chain immunoglobulin (Ig), and both light chains. Cell phenotype was examined with immunofluorescence techniques using antibodies against surface immunoglobulins (Slg) and the kappa and lambda light chains. Monoclonal antibodies were used against CD3, CD4, CD5, CD8, CD10, CD19, CD22, HLA‐DR, and TdT. Gene rearrangement analysis for monoclonality determination was carried out with restricted DNA (EcoR I and Hind III) hybridized with one of the following32P‐labelled probes: T‐cell receptor (TCR |gb), immunoglobulin heavy chain (JH), k light chain, and |gl light chain. Phenotyping of the cell population from the excised lymph node (LN) revealed the presence of 66% B‐cells and 35% T‐cells. Most of the B cells (94%) expressed μ heavy chain only. Expression of both light chains was negligible (k = 7% and λ = 2%). Gene rearrangement, which indicates monoclonality, was positive on the level of TCR, Ig heavy chain, and both light chains. The data obtained suggests a neoplastic transforming event in lymphoid stem cells, which preceded the subsequent differentiation process into either B or T lymphoma. Am. J. Hematol. 56:219–223, 1997. © 1997

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<219::AID-AJH4>3.0.CO;2-#

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractA number of chromosome aberrations occur nonrandomly as the sole aberration in malignant and premalignant hematological disorders. They imply very different prognoses. For most of them the survival consequences have been established. For trisomy 8, which is the most frequent numerical aberration in myeloid disorders, the prognostic implications have not been investigated. In order to clarify survival in patients with trisomy 8 as the sole aberration, the literature was searched for such cases. In 115 patients survival data were available. In 103 (89.6%), a myeloid disorder had been diagnosed. Acute myeloid leukemia (AML) or a myelodysplastic syndrome (MDS) occurred in 100 cases (87.0%). The median survival was found to be 17.1 months. On multivariate survival analysis (Cox), age above 60 and a leukemic diagnosis were found to be independent adverse prognostic indicators. MDS patients survived significantly longer (median 21 months) than AML patients (median 15 months). In MDS age and in AML the trisomy 8 clonal size was an independent prognostic factor. An unexpected observation was a clear male preponderance in trisomy 8 MDS (about two‐thirds of cases). In trisomy 8 AML an approximate 1:1 ratio was found. Browsing of Mitelman's catalog confirmed these ratios. Am. J. Hematol. 56:224–229, 1997. © 1997 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<224::AID-AJH5>3.0.CO;2-Z

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractWe compared the sensitivity and specificity of the two metabolite tests, methylmalonic acid (MMA) and total homocysteine (Hcy) in serum, and serum cobalamin (Cbl) in patients referred to our hospital because of suspected cobalamin deficiency and a serum cobalamin value at the referring unit<200 pmol/L. All 111 patients included were investigated using upper gastrointestinal endoscopy with biopsy specimens taken from the gastric and duodenal mucosa to find a morphological basis for cobalamin malabsorption as well as the Schilling test for the validation of the serum tests. All patients were treated with cobalamin and new blood samples were taken after 4 weeks. We found no difference in sensitivity and specificity between serum MMA, Hcy, and Cbl in identifying patients with and without conditions compatible with cobalamin malabsorption. Elevated serum MMA and Hcy were also found in about 15% of the group of patients with normal Schilling tests and without a morphological basis for cobalamin malabsorption. Moreover, most patients in this group responded with decreased values of the metabolite tests following cobalamin treatment, suggesting that neither elevated metabolites nor a decrease in these values following cobalamin treatment are specific for cobalamin deficiency. Am. J. Hematol. 56:230–238, 1997. © 1997 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<230::AID-AJH6>3.0.CO;2-Y

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractExpression of fetal hemoglobin (Hb F) is under polygenic control involving determinants both linked and unlinked to the β‐globin gene cluster on chromosome 11. Variations in the DNase I‐hypersensitive site 2 of the locus control region (LCR‐HS2) and a C → T change at position −158 from the Gγ‐gene (detected as anXmnI polymorphism) correlate with the high level of Hb F expression in patients with sickle‐cell anemia and β‐thalassemia. Interpretation of data under these conditions of anemic stress is difficult because the preferential survival of Hb F‐containing erythrocytes (F‐cells) may not reflect the true status of Hb F expression. We investigated the relationship between these markers and Hb F expression in terms of F‐cell levels in 48 unrelated non‐anemic AS heterozygotes from Sicily. The βS‐chromosome of all these individuals was of the Benin haplotype and they differed only by their βAchromosomes. We demonstrate that F‐cell expression is more strongly associated with LCR‐HS2 polymorphism than withXmnI polymorphism. The observed association betweenXmnI polymorphism and Hb F expression is very likely to be due to linkage disequilibrium with LCR‐HS2 sequences. Am. J. Hematol. 56:2

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<239::AID-AJH7>3.0.CO;2-Y

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractUltrastructure of platelets with the localization of platelet peroxidase and fibrinogen through 3‐min 47°C hot‐spring bathing was investigated in eight healthy volunteers. The mean sublingual temperature rose about 1.8°C 5 min after the start of bathing. The frequencies of fold, pseudopods, vacuoles, and centralization were increased after bathing. Platelet peroxidase activity was decreased after bathing. Furthermore, fibrinogen was decreased in α‐granules after bathing. Thus, hyperthermal stress in vivo may activate platelets, resulting in consumption of platelet peroxidase and fibrinogen. Am. J. Hematol. 56:244–247, 1997. © 1997 Wile

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<244::AID-AJH8>3.0.CO;2-X

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractTo detect and characterize parvovirus B19 infection during the course of progressive immune deficiency from human immunodeficiency virus (HIV), ten subjects enrolled in the Multicenter Hemophilia Cohort Study were followed for 6.4 to 15 years from HIV seroconversion through extreme immune deficiency. Four to five sera or plasma samples from each subject, collected at predetermined CD4+lymphocyte levels, were tested for immunoglobulin G (IgG) and M (IgM) B19 antibodies and DNA. All 42 samples were positive for B19 IgG antibodies, and three were weakly positive for IgM antibodies. Only one sample, collected coincident with HIV seroconversion, was unequivocally positive for B19 DNA. No persistent hematologic adverse effects of B19 infection were observed. Thus, although B19 IgG antibodies are highly prevalent among HIV‐infected persons with hemophilia or related disorders, B19 viremia and its hematologic consequences were not detected, even with severe depletion of CD4+lymphocytes. If primary B19 infection occurs after immune deficiency, however, the consequences may be more adverse. Am. J. Hematol. 56:248–251, 1997. © 1997 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<248::AID-AJH9>3.0.CO;2-X

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractPatients with sickle‐cell anemia treated with hydroxyurea may have significant reduction in frequency and severity of pain episodes. However, previous clinical trials show a variable response to hydroxyurea. Criteria which can be used to select patients who are likely to respond to hydroxyurea treatment would be useful. Our laboratory has previously demonstrated an inverse linear relationship between the total number of burst‐forming unit‐erythroid (BFU‐E) colonies and fetal hemoglobin levels in sickle‐cell patients treated with hydroxyurea. In the present report, an in vitro cell culture system was established to evaluate the effects of hydroxyurea on BFU‐E colony growth and induction of fetal hemoglobin production. Five Hb SS patients who were not previously treated with hydroxyurea and three Hb SS patients who failed to respond to hydroxyurea treatment were included in the study. The results show that the number of BFU‐E colonies is decreased from 153.7 to 7.2 per 3 × 105mononuclear cells, whereas fetal hemoglobin levels were increased from 5.1 to 19.4% in the presence of hydroxyurea in vitro in cultured erythroid progenitors, which were derived from 5 patients before treatment. The number of BFU‐E colonies decreased from 153.7 to 2.0 per 3 × 105mononuclear cells in the in vitro cultures obtained from serial peripheral blood samples over a 9‐ to 20‐week period of oral hydroxyurea therapy. A simultaneous rise in fetal hemoglobin level from 10.2 to 28.6% in the peripheral blood over the same period of hydroxyurea therapy was also observed. Our results demonstrate that the increase in fetal hemoglobin levels in cells treated with hydroxyurea in vitro is comparable to the rise of fetal hemoglobin production following hydroxyurea therapy in these patients. On the contrary, these findings were not observed in three previously non‐responsive sickle‐cell patients. These results suggest that the changes in number of BFU‐E colonies and fetal hemoglobin levels after in vitro exposure to hydroxyurea may be a useful approach to select sickle‐cell patients who will respond to hydroxyurea therapy. Am. J. Hematol. 56:252–25

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199712)56:4<252::AID-AJH10>3.0.CO;2-B

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY