Guess what: Chronic 13q14.3+/CD5-/CD23+ lymphocytic leukemia in blood and t(11;14)(q13;q32)+/CD5+/CD23- mantle cell lymphoma in lymph nodes!

We report a case of a patient with two B-cell lymphoproliferative disorders: CD5(-)/CD23(+) B-cell chronic lymphocytic leukemia and CD5(+)/CD23(-) mantle cell lymphoma. These disorders were diagnosed simultaneously based on flow cytometry, immunohistochemistry, fluorescence in situ hybridization, and polymerase chain reaction-based molecular studies. The B-cell lymphocytic leukemia clone predominated in the blood and bone marrow, whereas the mantle cell clone predominated in lymph nodes.     

慢性淋巴细胞系统白血病免疫表型分析

目的：研究国内慢性淋巴细胞系统折血病的免疫表型特点。方法：采用单参数和多参数流式细胞术分析了163例慢性淋巴细胞系统白血病的免疫表型。结果：71.8％（117/163）患者共表达CD5和B细胞标志。采用WHO引用的计分系统，将病例分为B-慢性淋巴细胞白血病（B-CLL），毛细胞白血病（HCL）和其他B淋巴细胞增殖性疾病。典型的B-CLL表达CD5、CD23、CD20、CD19、HLA-DR，但仍有部分患者表达CD22、CD11c、CD25和FMC7。CD103似为HCL最特异的标志。但仅仅依靠免疫表型难以鉴别非典型B-CLL、B细胞-幼淋巴细胞白血病（B-PLL）和外套细胞淋巴瘤（MCL），细胞遗传学或分子生物学检查将有助于鉴别诊断。以同一标本中残存的正常淋巴细胞为内参照，计算前向角光散射（FSC）指数和抗原表达指数，可定量地表示细胞的大小和抗原表达的强度，使不同的标本具有可比性。结论：免疫表型分析是诊断慢性淋巴细胞系统白血病非常有用的依据。     

Diminished expression of CD19 in B-cell lymphomas

BACKGROUND: CD19 is expressed on most B-cell lymphomas; however, the frequency and types of B-cell lymphomas with low-level expression of CD19 are not well characterized. METHODS: We reviewed flow cytometric histograms specifically for decreased CD19 expression on 349 cases analyzed by the Flow Cytometry Laboratory at University Hospitals of Cleveland (Cleveland, Ohio). Results of flow cytometry were correlated with the morphologic diagnosis. RESULTS: Of the cases reviewed, 125 (36%) showed a visible decrease in CD19 expression compared with normal B lymphocytes. Decreased CD19 expression was noted in 79% of follicular lymphomas (27 of 34), 36% of small lymphocytic lymphomas/chronic lymphocytic leukemias (82 of 228), 31% of mantle cell lymphomas (4 of 13), 24% of diffuse large B-cell lymphomas (8 of 33), and 13% of marginal zone B-cell lymphomas/lymphoplasmacytoid lymphomas (4 of 30) and was not observed in any Burkitt lymphoma (0 of 5) or hairy cell leukemia (0 of 6). Decreased CD19 expression was significantly more frequent in follicular lymphomas than in other lymphoma subtypes (P < 0.001). No significant difference was observed in the frequency of decreased CD19 expression based on histologic grade of follicular lymphoma. CONCLUSIONS: Diminished expression of CD19 expression occurs frequently in B-cell lymphomas, in particular follicular lymphoma, and may be helpful in identifying B-cell lymphoma cells in complex cell mixtures such as bone marrow specimens.     

Phenotypic classification of malignant lymphoma

The phenotypic characters of the lymphoma cell are important in the diagnosis of this disease. We recently tested whether the flow cytometry with fresh biopsy sample might be useful in the diagnosis of the lymphoma. In our date, 1. a rise and fall of the surface immunoglobulin kappa/lambda ratio indicated the monoclonal proliferation of the B-cell, 2. the increased proportion of the CD5/CD23 double positive cells indicated B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma, 3. the decreased proportion of the CD2 positive cells and the increased proportion of the CD19 positive cells indicated B-cell lymphoma. These findings suggest that the flow cytometry is of adjunctive importance in making a diagnosis of the lymphoma.     

Unsupervised immunophenotypic profiling of chronic lymphocytic leukemia

BACKGROUND: Proteomics and functional genomics have revolutionized approaches to disease classification. Like proteomics, flow cytometry (FCM) assesses concurrent expression of many proteins, with the advantage of using intact cells that may be differentially selected during analysis. However, FCM has generally been used for incremental marker validation or construction of predictive models based on known patterns, rather than as a tool for unsupervised class discovery. We undertook a retrospective analysis of clinical FCM data to assess the feasibility of a cell-based proteomic approach to FCM by unsupervised cluster analysis. METHODS: Multicolor FCM data on peripheral blood (PB) and bone marrow (BM) lymphocytes from 140 consecutive patients with B-cell chronic lymphoproliferative disorders (LPDs), including 81 chronic lymphocytic leukemia (CLLs), were studied. Expression was normalized for CD19 totals, and recorded for 10 additional B-cell markers. Data were subjected to hierarchical cluster analysis using complete linkage by Pearson's correlation. Analysis of CLL in PB samples (n = 63) discovered three major clusters. One cluster (14 patients) was skewed toward "atypical" CLL and was characterized by high CD20, CD22, FMC7, and light chain, and low CD23. The remaining two clusters consisted almost entirely (48/49) of cases recorded as typical BCLL. The smaller "typical" BCLL cluster differed from the larger cluster by high CD38 (P = 0.001), low CD20 (P = 0.001), and low CD23 (P = 0.016). These two typical BCLL clusters showed a trend toward a difference in survival (P = 0.1090). Statistically significant cluster stability was demonstrated by expanding the dataset to include BM samples, and by using a method of random sampling with replacement. CONCLUSIONS: This study supports the concept that unsupervised immunophenotypic profiling of FCM data can yield reproducible subtypes of lymphoma/chronic leukemia. Expanded studies are warranted in the use of FCM as an unsupervised class discovery tool, akin to other proteomic methods, rather than as a validation tool.     

Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia

CD5-expressing B lymphocytes from patients with selected chronic lymphoproliferative disorders were used to determine whether monoclonal populations of CD5+ human B cells produce autoantibodies. CD5+ B cells from 19 patients with chronic lymphocytic leukemia (CLL) and one with diffuse well-differentiated lymphocytic lymphoma (DWDL) were cultured, with and without mitogenic stimulation, to obtain Ig from these cells. 17 of the 20 samples produced Ig in vitro. mAb from nine of the 17 patients were reactive with either IgG, ssDNA, or dsDNA. In every instance, the autoantibodies displayed monotypic L chain usage that correlated precisely with the L chain expressed on the CD5+ leukemic B cell surface. These monoclonal autoantibodies varied in their degree of antigenic specificity; some were quite specific, reacting with only one antigen, whereas others were polyspecific, reacting with two or all three autoantigens tested. Three features distinguish these autoantibodies from those observed in prior studies of CD5+ B cells. First, they are clearly the products of monoclonal populations of CD5+ cells; second, several react with dsDNA, a specificity not previously reported and often seen in association with significant autoimmune disorders; and third, two of the monoclonal autoantibodies secreted by the CD5+ clones were of the IgG class. Although not all of the Ig-producing, CD5-expressing clones elaborated mAbs reactive with the autoantigens tested, greater than 50% did. It is possible that with a broader autoantigenic panel or with larger quantities of CLL/DWDL-derived Ig, even more autoantibody-producing clones might be identified. These studies may have important implications for the antigenic specificity of subsets of human B lymphocytes as well as for lymphoproliferative and autoimmune disorders in general.     

Effect of interferon-alpha on CD20 antigen expression of B-cell chronic lymphocytic leukemia

Chimeric CD20 monoclonal antibody as alternative therapy in relapsed low-grade non-Hodgkin's lymphoma (NHL) has produced responses in nearly 50% of patients. Augmenting CD20 expression on tumor cells and/or inducing its expression may increase the cell kill and effectiveness of antibody therapy. Peripheral blood lymphocytes from 19 patients with B-cell chronic lymphocytic leukemia (B-CLL) were incubated in vitro in the presence of interferon-alpha (IFN-alpha) (500 U/ml and 1,000 U/ml) for 24 and 72 hours. The effect on CD20 expression was studied by flow cytometry. The differences in the percentage positivity, the mean fluorescence intensity (MFI), and the product of percentage positivity and MFI were used to assess upregulation. There was a significant upregulation of CD20 expression on B cells seen at both concentrations after 24-hour priming (p < 0.01). B-CLL cells cultured for 72 hours in the presence of IFN-alpha also showed upregulation of CD20 expression; however, the degree of upregulation was much lower than that seen at 24 hours. There was no statistically significant increase in CD20 antigen expression on normal lymphocytes following cytokine exposure. These results suggest that IFN-alpha priming may augment the effectiveness of antibody therapy by directly upregulating CD20 antigen expression in addition to its indirect action through effector cells of the host.     

Different levels of CD52 antigen expression evaluated by quantitative fluorescence cytometry are detected on B-lymphocytes, CD 34+ cells and tumor cells of patients with chronic B-cell lymphoproliferative diseases

BACKGROUND: The success of treatment using monoclonal antibodies in oncology is influenced by, among other factors, the level of target antigen expression on tumor cells. The authors analyzed the intensity of the CD52 antigen expression in patients with chronic lymphoproliferative diseases and compared them with B-lymphocytes of a healthy population and CD34(+) cells in peripheral blood stem cells (PBSC) grafts. METHODS: Recently diagnosed and previously untreated patients with B-cell chronic lymphocytic leukemia (B-CLL), mantle-cell lymphoma (MCL), or small lymphocytic lymphoma (SLL) were evaluated and compared with control group and CD34(+) cells. The intensity of CD52 was expressed in molecules of equivalent soluble fluorochrome units (MESF) and antibody-binding capacity (ABC). RESULTS: In the group of patients with B-CLL, the CD52 level on tumor cells (245 x 10(3) MESF; 107 x 10(3) ABC) was significantly lower than on B-lymphocytes of the control group (446 x 10(3) MESF; 194 x 10(3) ABC; P < 0.001) and SLL tumor cells (526 x 10(3) MESF; 229 x 10(3) ABC; P < 0.001). The CD52 antigen was expressed on a majority of CD34(+) cells, but its expression intensity was low (101 x 10(3) MESF; 44 x 10(3) ABC). CONCLUSIONS: Our data demonstrate differences in the intensity of the CD52 antigen expression between B-lymphocytes and tumor lymphocytes of B-CLL patients, and between B-CLL and SLL tumor cells. CD52 antigen is expressed at low level on CD34(+) cells.     

用流式细胞术从B淋巴增殖性疾病中鉴别脾边缘带淋巴瘤

脾边缘带淋巴瘤（Splenicmarginalzonelymphoma,SMZL）是一种相对少见的原发于脾脏的惰性B淋巴增殖性疾病,表现为外周血淋巴细胞计数和／或比例增高、脾大,而外周浅表淋巴结往往不大,需要应用诊断性脾切除病理检查得以确诊,但患者多数不能接受,早期诊断困难。本研究探索以流式细胞术（flowcytometry,FCM）为主的诊断途径的可行性。选取6例疑诊SMZL患者为研究对象,同时以10名骨髓健康供者及确诊的10例慢性淋巴细胞白血病（CLL）、3例毛细胞白血病（HCL）、3例淋巴浆细胞淋巴瘤／华氏巨球蛋白血症（LPL／wM）初诊患者为对照。对所有患者及对照组进行骨髓FCM免疫分型,所选抗体组合包括CD45、CD5、CD10、CD19、CD20、CD22、CD23、CD25、CD103、CD11c、CD123、κ、λ、CyclinD1等,同时结合骨髓细胞形态学检查。结果表明：6例疑诊sMzL患者表现为淋巴细胞增高和脾大。因外周淋巴结无肿大6例患者均未行淋巴结活检,仅1例患者行病理诊断性脾切除。经骨髓FCM免疫表型分析,除健康供者外均可发现骨髓中存在不同程度的异常成熟B细胞克隆,并通过CD5、CD10表达与否结合其他表型进一步与其他B细胞肿瘤鉴别。结果6例SMZL患者均CDl9＋、CD20＋,而CD10-,4例患者CD5-,2例CD5＋,而CD23、CD38、ZAP-70、CD11c、CD103、CD123、CyclinD1均不表达。骨髓细胞形态学检查可见有短绒毛的异常淋巴细胞,结合临床特征将6例患者诊断为SMZL。1例患者因合并脾功能亢进需要行脾切除,术后病理证实该病。10例CLL主要表达CD5、CD23之外;在3例HCL除表达CD11c、CD103、CD123,形态学上更有典型的”毛”;3例LPL／WM具有轻链限制性表达、IgM显著升高、浆样淋巴细胞增多的特点。结论：FCM免疫表型分析结合骨髓形态学可作为临床诊断SMZL有力的工具。     

Cancer antigen 125 levels in inflammatory bowel diseases

Background: Cancer antigen 125 (CA‐125) is a tumor marker used for the diagnosis and monitoring of ovarian carcinoma. It can also be elevated in endometriosis, inflammations, and in nongynecological malignancies. Up to date, serum CA‐125 levels in inflammatory bowel diseases (IBD) have not been studied before. Aim: To assess the levels of CA‐125 in patients with ulcerative colitis (UC) and Crohn's disease (CD). Methods: Serum levels of CA‐125 were investigated in 68 cases with UC (male/female: 47/21), 32 CD (male/female: 21/11), and 31 healthy controls (male/female: 16/15). Levels of CA‐125 were also compared among UC patients according to lesion location, severity, and activity of CD. Results: Serum CA‐125 levels were 17.29±24.50 U/ml, 15.56±20.74 U/ml, and 8.85±2.62 U/ml in patients with UC, CD, and healthy controls, respectively. Serum CA‐125 levels were significantly higher in UC compared to control group (P=0.001). Serum CA‐125 levels were higher in CD patients compared to control group but there was no significance (P=0.087). Serum CA‐125 levels were higher in pancolitis compared to distal type and left‐sided UC. Conclusions: Our data suggest that serum CA‐125 levels may be increased in patients with IBDs. J. Clin. Lab. Anal. 23:244–248, 2009. © 2009 Wiley‐Liss, Inc.     

脾原发性淋巴瘤超微病理诊断及流式细胞分析的研究

目的探讨诊断电镜(DEM)对脾原发性淋巴瘤的病理分型诊断,流式细胞术(FCM)检测瘤细胞DNA含量与其恶性程度及预后关系.方法应用透射电镜和流式细胞术观察分析41例脾原发性淋巴瘤超微结构和瘤细胞DNA含量.结果41例脾原发性淋巴瘤中霍奇金B细胞性淋巴瘤5例占12.20%,非霍奇金B细胞性淋巴瘤21例,占51.22%非霍奇金T免疫母细胞淋巴瘤11例,占26.83%;脾组织细胞性淋巴瘤3例,占7.31%;伴毛细胞淋巴瘤1例,占2.34%.FCM范围在0.77～2.06,DI均值1.12±0.37,其中二倍体肿瘤13例,占31.7%;异倍体肿瘤28例,占68.3%.低恶性组为13例,DI为1.12±0.37,中恶组17例,DI为1.45±0.25,高恶组11例,DI为1.71±0.19.低、中与高恶组相比,差异显著(P＜0.01).DI和超微病理组织学分型呈正相关关系.结论DEM为脾原发性淋巴瘤超微病理诊断提供了形态学标准,FCM脾淋巴瘤细胞DNA倍性,增殖活性的检测有助于脾原发性淋巴瘤恶性度和预后的判断.     

Soluble interleukin-2 receptor in hairy-cell leukemia: a reliable marker of disease

Summary The CD25 molecule, which corresponds to the p55 α chain of the interleukin-2 receptors, is strongly expressed by neoplastic cells in hairy-cell leukemia and is released in large amounts in the soluble form which is detectable in serum. In order to assess the reliability of the soluble interleukin-2 receptor as a disease marker in the management of patients with hairy-cell leukemia, we investigated serum levels in 35 untreated patients and in 2 patients with the hairy-cell leukemia variant. In 21 of 35 patients soluble receptor levels were also monitored during and after recombinant interferon-α therapy. Clinical and hematological parameters were also assessed. Soluble interleukin-2 receptor levels were extremely high at the time of diagnosis in patients with typical hairy-cell leukemia [32,722±27,001 vs. 331±145 units/ml in controls (mean±SD)], but not in patients with the leukemia variant. A progressive decrease in soluble interleukin-2 receptor levels paralleled the clinical response to treatment, although normal values were never detected, even in patients who achieved an apparent complete remission. After recombinant interferon-α discontinuation, disease recurrence was accompanied by a progressive increase to pre-treatment soluble receptor levels. Overall, a close correlation was found between soluble interleukin-2 receptor values and total tumor burden (r=0.84,P<0.001). On the basis of these data, soluble interleukin-2 receptor should be regarded as a key marker in the management of patients with hairy-cell leukemia.     

Ischemia-modified albumin in acute aortic dissection

Background: Acute aortic dissection (AOD) is associated with high mortality and early diagnosis and treatment are essential. Ischemia‐modified albumin (IMA) is a marker of myocardial ischemia whereas cardiac enzymes are released when myocardial necrosis occurs. We investigated, for the first time, whether IMA increases in AOD either at presentation or after surgery. Methods: We studied 46 consecutive patients with documented AOD; we also evaluated 13 consecutive patients with dilated ascending aortas scheduled for elective surgery and admitted for preoperative coronary angiography; 46 age‐matched normal subjects served as controls. Only patients with acute onset of symptoms were included. We evaluated IMA, cardiac enzymes, N‐terminal pro‐B‐type natriureticpeptide, albumin, C‐reactive protein (CRP), and D‐dimers on admission, 24 hr post‐operatively and 4 days post‐operatively. Duration from symptom onset to the first sample was 23±17 hr. Results: IMA did not differ between patients with AOD at presentation (93±19 U/ml), patients with chronic aneurysms (90±14 U/ml) and normal controls (91±9 U/ml). In addition, IMA did not change significantly after surgical repair. IMA, at baseline, however, correlated positively with time from symptom onset as well as CRP levels (P=0.05 and P=0.007, respectively). Conclusion: IMA is not elevated in AOD when blood sampling is performed within 23±17 hr after symptom onset nor increases after surgery. J. Clin. Lab. Anal. 24:399–402, 2010. © 2010 Wiley‐Liss, Inc.     

30例原发性小肠淋巴瘤病理分析

目的：研究原发性小肠淋巴瘤（PSIL）的病理特点。方法：对30例PSIL患者的组织标本行苏木精-伊红（HE）染色、免疫组化检查,其中2例行基因重排检查,并结合文献进行分析。结果：30例PSIL患者的病理诊断均为非霍奇金淋巴瘤（NHL）,其中B细胞来源23例（76.7%）、T细胞来源7例（23.3%）。其组织学类型分别为弥漫大B细胞淋巴瘤16例（53.3%）、黏膜相关淋巴组织（MALT型）B细胞淋巴瘤7例（23.3%）、外周T细胞淋巴瘤6例（20.0%）、自然杀伤（NK）/T细胞淋巴瘤1例（3.4%）。免疫组化结果示,30例PSIL均表达CD45,AE1/AE3均阴性,4例B细胞淋巴瘤EMA弱阳性。23例B细胞淋巴瘤均表达CD20和CD79α,7例T细胞淋巴瘤均表达CD3和CD45RO。NK/T细胞淋巴瘤还表达CD56和TIA-1。16例弥漫大B细胞淋巴瘤有6例（37.5%）表达Bcl-2蛋白,10例（62.5%）表达MIB-1。7例MALT型B细胞淋巴瘤中有5例（71.4%）表达Bcl-2,1例（14.3%）表达MIB-1。基因重排结果示,2例B细胞淋巴瘤均呈Fr2A、Fr3A阳性,TcR阴性。结论：PSIL大多为B细胞来源的NHL,最常见的组织学类型是弥漫大B细胞淋巴瘤。Bcl-2、MIB-1的阳性率与肿瘤病理分型相关。     

肝血管内大B细胞性淋巴瘤2例临床病理观察

目的探讨肝血管内大B细胞性淋巴瘤的临床病理特征、诊断与鉴别诊断、治疗及预后。方法回顾性分析2例肝血管内大B细胞性淋巴瘤患者的临床资料、组织病理学形态和免疫组化结果。结果光镜下肝窦内和小血管内可见较多具有明显异型性的淋巴样细胞浸润,汇管区可见慢性炎细胞浸润,亦可见少许异型淋巴细胞样细胞,未见明确纤维化。免疫组化示CD20、PAX5弥漫(+),CD3散在少许(+),Ki-67阳性率为70%,AE1/AE3、CD117和CD56均(-);其中例1 CD5弥漫(+)。结论血管内大B细胞性淋巴瘤是一种具有高度侵袭性的结外弥漫性大B细胞性淋巴瘤的亚型,由于该病临床表现多样及不典型性,造成了部分患者的诊断困难,因此,掌握临床病理及免疫组化特征对该病的诊断和鉴别诊断具有重要意义。     

Clinical significance of monoclonal B cells in cerebrospinal fluid

BACKGROUND: Morphologically malignant lymphocytes in the cerebrospinal fluid (CSF) are highly suggestive of central nervous system involvement by lymphoid malignancy. Although flow cytometry is increasingly used to detect a monoclonal B-cell population in the CSF, the significance of this finding in the absence of morphologically identifiable malignant cells is unknown. METHODS: We reviewed CSF flow cytometric results in 32 patients studied at a single institution over 5 years and identified patients who had monoclonal B-cells in the CSF. Clinical presentation and course were reviewed. RESULTS: Twelve patients had a monoclonal B-cell population in the CSF, but only three had clinical evidence of malignant CNS disease. Of the other nine patients, 4 had nonmalignant neurologic disease and five had a lymphoproliferative disorder: chronic lymphocytic leukemia (n = 4) and mantle cell lymphoma (n = 1). In patients who had chronic lymphocytic leukemia and mantle cell lymphoma, the monoclonal B-cell population was small and had an immunophenotype identical to that of circulating malignant B cells. None of these nine patients developed clinical evidence of malignant CNS involvement during follow-up. CONCLUSION: In patients who have indolent B-cell malignancies, the presence of monoclonal B cells in the CSF may not be diagnostic of clinically significant CNS involvement by a lymphoid malignancy.     

恶性血液病细胞中tankyrase表达与端粒酶活性关系研究

为研究以白血病为主的恶性血液病细胞中端粒酶活性正向调控基因tankyrase的表达与端粒酶活性的关系并初步探讨tankyrase对端粒酶活性调控的机理和意义 ,以实时定量RT PCR技术对髓细胞系白血病细胞株K5 6 2 ,HL 6 0 ,U937,NB4 ,THP 1,HEL ,Dami,T淋巴细胞性白血病细胞株 6T CEM ,Jurkat和B细胞淋巴瘤细胞株Raji中tankyrase的表达进行检测 ,同时检测端粒酶逆转录酶hTERT的表达确定端粒酶活性 ,并以经磁珠分离的正常人CD3 ,CD19 和CD33 细胞和 10份正常人骨髓单个核细胞做对照。结果发现 :tankyrase在恶性血液病细胞株中的表达明显高于正常对照 (U =19,P <0 .0 1) ,其中髓系白血病细胞株中的表达高于正常人CD33 细胞 ,T淋巴细胞性白血病细胞株和B细胞淋巴瘤细胞株中的表达分别高于正常人CD3 和CD19 细胞。髓系恶性血液病细胞株tankyrase的表达 (0 .0 0 32± 0 .0 0 10 )明显低于淋系恶性血液病细胞株的表达 (0 .0 12± 0 .0 0 16 ) (F =2 3,P <0 .0 1)。Tankyrase与hTERT的表达呈正相关 (相关系数为 0 .395 ,P <0 .0 5 )。结论 :tankyrase在恶性血液病细胞株中呈高表达 ,与端粒酶活性呈正相关 ,提示tankyrase可能是恶性血液病中端粒酶活性增高的原因之一。     

Effect of low-dose heparin on fibrinogen levels in patients with chronic ischemic heart disease

Several prospective studies have demonstrated that high plasma fibrinogen levels are associated with an increased risk of ischemic heart disease. Since in most patients an increased thrombin generation has been reported, we investigated whether the control of thrombin generation could affect plasma fibrinogen levels. Forty male outpatients (20 asymptomatic with previous myocardial infarction and 20 with stable effort angina) were enrolled in a randomized medium-term (6 months) cross-over study. Clottable fibrinogen, according to Clauss, prothrombin fragment 1+2, thrombin-antithrombin complex, and fibrinopeptide A were evaluated in relation to treatment with low-dose heparin. After a 15-day wash-out period, during which patients had been treated only with nitrates if needed, patients were allocated to two sequential periods of treatment with standard heparin (12,500 U, subcutaneously daily) plus antianginal treatment or antianginal treatment alone, separated by a second 15-day wash-out period. At the end of the treatment period with low-dose heparin significant decreases in the plasma fibrinogen (2.5±0.6 g/l vs. 3.3±0.5 g/l,P<0.001), prothrombin fragment 1+2 (1.4±0.5 nmol/l vs. 1.9±0.7 nmol/l,P<0.001), thrombinantithrombin (4.5±2.4 ng/ml vs. 9.7±3.6 ng/ml,P<0.001), and fibrinopeptide A (2.1±1.1 ng/ml vs. 3.5±2.1 ng/ml,P<0.001) were observed compared with the period without heparin. The present results indicate that low-dose heparin can effectively control the increased abnormal thrombin generation and elevated fibrinogen levels in patients with ischemic heart disease, possibly decreasing the risk of cardiovascular death.     

Autoantibodies to B Lymphocytes in a Patient with Hypoimmunoglobulinemia: CHARACTERIZATION AND PATHOGENIC ROLE

In a young woman with ulcerative colitis, hypoimmunoglobulinemia, and humoral immunodeficiency, lymphocyte counts vary between 600 and 1,000 per mm(3) with 0.5-1.5% bone marrow-derived (B) cells and 98-99% thymus-derived (T) cells. Anti-lymphocyte antibodies were detected by immunofluorescence and by microlymphocytotoxicity with increased reactivity at +4 degrees C. They belonged to the IgM class and were polyclonal. Studies performed with various normal lymphocyte subpopulations, several lymphoblastoid cell lines and lymphocytes from immunodeficiency patients showed that these antibodies reacted with B cells. The corresponding antigen(s) is distinct from membrane-bound immunoglobulins, is not an alloantigen, and is probably unrelated to the la-like molecules. Pokeweed mitogen stimulated B cells appear to lose this antigen. Cells from various lymphoproliferative disorders were tested. T-derived and "non T-non-B" leukemic cells did not react with the antibody. Malignant cells from B-derived lymphomas and prolymphocytic leukemias were reactive. The incidence of positivity of the leukemic cells among patients with common B chronic lymphocytic leukemia was surprisingly low (one-third of the patients).The autoantibody nature of the anti-B-cell antibodies and their pathogenic role in the genesis of the patient's hypoimmunoglobulinemia was demonstrated by the effect of removal of antibodies by massive plasmaphereses which were followed by a dramatic and transitory increase of B-cell figures. Whereas most primary immunodeficiency syndromes appear to result from an arrest in the differentiation capabilities of immunologically competent cells, autoantibodies to circulating B lymphocytes may be incriminated in the pathogenesis of some cases of hypogammaglobulinemia.     

The surface morphology of human B lymphocytes as revealed by immunoelectron microscopy

Surface immunoglobulins (sIg) were detected on human lymphocytes by immunoelectron microscopy with peroxidase-conjugated antibodies. Blood, marrow, and thymus cells from normal individuals and patients with lymphoproliferative disorders were examined. Samples were fixed before exposure to specific reagents. Normal lymphocyts with detectable sIg, i.e. B lymphocytes, were characterized by a villous surface; nonlabeled blood lymphocytes and thymocytes were smooth cells. Intermediate cells were also found which in sections appeared moderately villous and labeled, thus identified as B lymphocytes. Further evidence for a relationship between villous surface and sIg was given by the finding of a few lymphocytes with polar concentration of labeled microvilli. In chronic lymphocytic leukemia patients, most cells exhibited a villous surface with parallel variations of the number of microvilli and of anti-immunoglobulin-binding capacity. However, some labeled smooth blastic cells were also observed. On the other hand, abnormal lymphocytes from Sézary's syndrome which could exhibit segments of villous membrane had no detectable sIg. This study confirms that in most cases human B lymphocytes have a characteristic surface appearance and that the detection of sIg in normal lymphocytes correlates with the presence of microvilli.