Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes

Two major types of lymphocytosis of large granular lymphocytes (LGLs) were observed. The proliferating LGLs in each type had distinct immunophenotypes, functional characteristics, and probably belonged to different cell lineages. The more common form (Type A) consisted of cells derived from the T cell lineage and had the T suppressor/cytotoxic phenotype (T11+, T3+, T8+). The expression of the Leu 7 and HLA-DR antigen was variable. These cells did not have natural killer (NK) function but showed a variable degree of antibody-dependent cell-mediated cytotoxic (ADCC) activity. Neutropenia was invariably present and rheumatoid arthritis and autoantibodies were frequent associations. These lymphocytes had many similarities to the major type of LGLs present in normal adult bone marrow. The other type of LGL lymphocytosis (Type B) consisted of cells lacking the antigens T3 and T8 but expressing M1 and NKH1. These cells possessed strong NK and ADCC activity but their cell lineage was not clear. Neutropenia and autoimmune phenomena were not detected. The cytochemical characteristics of the LGL granules from both types of patients were similar but differences in ultrastructure were observed. LGLs from Type B patients proliferated in the presence of Interleukin 2 (IL-2) and 12- O-tetradecanoyl-phorbol-13 acetate (TPA). Significant changes in their basic T11+, T3-, T8- phenotype were not observed. IL-2 and TPA, however, had profound influence on the NK function of the cells with enhancement in the case of IL-2 and marked suppression when stimulated by TPA.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.      

急危重病人血流动力学最佳化状态治疗研究的Meta分析

目的　探讨有关急危重病人血流动力学状态达到最佳化治疗研究中肺动脉导管 (Swan -Ganz)与复苏治疗的关系 ,评估生理、临床、治疗等方面因素对复苏治疗效果的影响。方法　从MEDLINE(英文医学文献资料网库 )中搜集所有与Swan -Ganz和血流动力学状态有关的 71篇研究文献。按照限定条件进行筛选 :①病人类型 :急性病 ,高危外科手术病人 ,创伤 ;②达到血流动力学指标正常值或超常值标准 ;③控制组死亡率 >2 0 % (危重组 )或 <15 % (一般组 ) ;④治疗后达到血流动力学指标的早晚 ;其中 2 1项研究接受Meta分析。结果　在危重组 ,早期达到血流动力学超常值治疗 ,2 1项研究中的 7项显示在控制组与治疗组之间死亡率有显著性的差别 (P <0 0 5 ) ;而晚期达到血流动力学超常值治疗的 6项研究 ,两组之间死亡率无显著性的差别 (P >0 0 5 )。在一般组 ,达到血流动力学正常值治疗的 5项研究和超常值治疗的 3项研究显示 ,控制组与治疗组之间死亡率无显著性的差别。结论　经Swan -Ganz引导早期达到血流动力学超常值治疗 ,能降低重病组的死亡率。     

Patient preference and willingness to pay for transient elastography versus liver biopsy: A perspective from British Columbia

BACKGROUND:

The cost of liver biopsy (LB) is publicly funded in British Columbia, while the cost of transient elastography (FibroScan [FS], Echosens, France) is not. Consequently, there is regional variation regarding FS access and monitoring of liver disease progression.

OBJECTIVE:

To evaluate patient preference for FS versus LB and to assess the willingness to self-pay for FS.

METHODS:

Questionnaires were distributed in clinic and via mail to LB-experienced and LB-naive patients who underwent FS at Vancouver General Hospital, Vancouver, British Columbia.

RESULTS:

The overall response rate was 76%. Of the 422 respondents, 205 were LB-experienced. The mean age was 53.5 years, 50.2% were male, 54.7% were Caucasian, 38.2% had hepatitis C and 26.3% had an annual household income >$75,000. Overall, 95.4% of patients preferred FS to LB. FS was associated with greater comfort than LB, with the majority reporting no discomfort during FS (84.1% versus 7.8% for LB), no discomfort after (96.2% versus 14.6% LB) and no feelings of anxiety after FS explanation (78.2% versus 12.7% LB). FS was also associated with greater speed, with the majority reporting short test duration (97.2% versus 48.3% LB) and short wait for the test result (95.5% versus 30.2% LB). Most (75.3%) respondents were willing to self-pay for FS, with 26.3% willing to pay $25 to $49. Patients with unknown liver disease preferred LB (OR [FS preference] 0.20 [95% CI 0.07 to 0.53]).

CONCLUSIONS:

FS was the preferred method of assessing liver fibrosis among patients, with the majority willing to self-pay. To ensure consistency in access, provincial funding for FS is needed. However, LB remains the procedure of choice for individuals with an unknown diagnosis.     

Herpes simplex virus hepatitis in pregnancy. Two patients successfully treated with acyclovir

Two cases of herpes simplex virus hepatitis in pregnancy are presented. Each case was characterized by extremely high serum aminotransferase levels with minimal bilirubin elevation. In both cases, liver biopsy was instrumental in arriving at the diagnosis. In addition, computed tomography showed a radiographic appearance of the liver not characteristically seen in other hepatic disorders of pregnancy. A high index of suspicion in the second case led to early recognition and treatment. Despite the presence of fulminant liver failure and evidence of herpes encephalitis in the other case, institution of therapy with acyclovir was associated with complete recovery in both patients. The present cases are compared and contrasted with the literature. The incidence of two cases within a 6-month period suggests that herpes simplex virus hepatitis in pregnancy may occur more frequently than previously reported.     

T-cell receptor gene rearrangement in T-cell large granular leukocyte leukemia: preferential V alpha but diverse J alpha usage in one of five patients

T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T- cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T-cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR alpha- and beta-chain genes in patients with T-gamma LPD, we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common V alpha nor a common J alpha segment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the beta chain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common V alpha (V alpha 19.1). In contrast to this common V alpha usage, there was a marked diversity of the J alpha segments and N-region addition that were associated with the V alpha 19.1 segment. This pattern of common V alpha usage associated with different N and J alpha segments suggests an immune-mediated selection process affecting the TCR alpha chain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreactivity conferred by the selected TCR alpha chain and that this autoreactivity might be implicated in this patient's anemia.     

华人、马来人、印度人中白细胞介素4及受体基因多态性与血清总IgE水平的关系

既往研究提示白细胞介素4(IL-4)、白细胞介素4受体(IL-4RA)基因与血清总IgE水平、过敏性疾病有关。然而结论并不一致。我们的研究目的在于调查华人、马来人及印度人中IL-4、IL-4RA的3个基因位点的基因型(C590T、Ile50Val、Q576R)与血清总IgE水平是否存在相关性。