Identification and culture of Kaposi's sarcoma-like spindle cells from the peripheral blood of human immunodeficiency virus-1-infected individuals and normal controls [see comments]

We examined 26 patients with human immunodeficiency virus-1 (HIV-1)- associated Kaposi's sarcoma (KS), and 76 HIV-1-infected (HIV-1+) people without KS or uninfected (HIV-1-) controls for the presence of circulating KS-like spindle cells. Adherent cells that had spindle morphology and several characteristics of spindle cells of KS lesions (KS cells) were identified in the peripheral blood mononuclear cell fraction only after culture in the presence of conditioned medium (CM) from activated lymphocytes. The peripheral blood-derived spindle cells (PBsc) expressed a variety of endothelial cell markers, such as Ulex europaeus I lectin, EN4, EN2/3, EN7/44, CD13, CD34, CD36, CD54, ELAM-1, and HLA-DR. However, they were negative for CD2, CD19, PaIE, and factor VIII-related antigen. The PBsc produced angiogenic factors as evidenced by the ability of CM from these cells to promote growth of normal vascular endothelial cells. In addition, subcutaneously injected PBsc stimulated angiogenesis in vivo in athymic nude mice. We determined that the number of PBsc grown from the peripheral blood of HIV-1+ patients with KS or at high risk to develop KS were increased by 78- fold (P = .0001) and 18-fold (P = .005), respectively, when compared with HIV-1- controls. The number of spindle cells cultured from the HIV- 1+ patients at low risk for developing KS, eg, HIV-1+ injection drug users, showed no statistical increase when compared with HIV-1- controls. The presence of increased PBsc with characteristics of KS cells in HIV-1+ KS patients or patients at high risk for developing KS gives insights into the origin of KS cells and may explain the multifocal nature of the disease. In addition, this may be useful in predicting the risk of KS development.     

Discrepancy between IIA phenotype and IIB genotype in a patient with a variant of von Willebrand disease

Type IIA and IIB von Willebrand disease (vWD) result from qualitative abnormalities of von Willebrand factor (vWF) characterized by an absence in plasma of high molecular weight vWF multimers and an abnormal reactivity of vWF towards platelet glycoprotein (GP) Ib, which is decreased in type IIA and increased in type IIB. In this report, we describe the case of a patient having a IIA vWD phenotype associated with an intermittent thrombocytopenia atypical in this subtype but observed in type IIB vWD. The patient plasma vWF showed an absence of high molecular weight and intermediate multimers and had a decreased binding capacity to GPIb. The affinity of botrocetin was normal for plasma vWF from the propositus. Analysis of the propositus vWF gene showed the presence of a substitution Val 551 to Phe of the mature vWF subunit. This mutation is localized within a 509-695 disulphide loop of the vWF that plays an important role in the binding to GPIb and is where most of the molecular defects described so far were associated with type-IIB vWD. We have reproduced the Val 551 Phe substitution onto the vWF cDNA, expressed it in COS-7 cells, and performed structural and functional analysis of the mutant recombinant protein (rvWFPhe 551). The rvWFPhe 551 had a normal multimeric structure and showed the capacity to spontaneously interact with GPIb. Botrocetin had a decreased affinity for rvWFPhe 551. In conclusion, the Val 551 Phe mutation modifies the affinity of vWF for platelet GPIb, as does a type IIB mutation, and may be responsible for the thrombocytopenia of the patient and the clearance of the high molecular weight and intermediate- sized multimers of vWF from the plasma. The study of the rvWFPhe 551 has confirmed the discrepancy between the IIA phenotype and the IIB genotype of the patient.     

Antiretroviral pill count and clinical outcomes in treatment‐naïve patients with HIV infection

Objectives

Treatment guidelines recommend single‐tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple‐pill formulations of the same regimen.

Methods

We selected treatment‐naïve patients starting one‐, two‐ or three‐pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one‐pill regimen or a three‐pill regimen.

Results

Among 11 739 treatment‐naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow‐up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01‐1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84‐1.68). We estimate that 77 patients would need to be exposed to a one‐pill regimen rather than a three‐pill regimen for 1 year to avoid one additional AIDS event or death.

Conclusions

This particular single‐tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple‐pill formulations.

     

双腔起搏器自动模式转换功能的临床应用

为观察双腔起搏器自动模式转换功能在房性心律失常治疗中的应用效果 ,对置入具自动模式转换功能起搏器的 31例患者分别于术后第 4天、1个月及每隔 3个月进行一次跟踪随访 ,观察房性心律失常的发生情况和起搏器自动模式转换情况及临床症状。全部病例随访 1～ 18个月 ,出现阵发性心房颤动、心房扑动及房性心动过速 76阵次 ,起搏器由DDD(R)自动转换成DDI(R)模式 72阵次 ,患者自觉心悸 8阵次。结论 :自动模式转换功能可使起搏器在患者发作房性心动过速时发挥对心室的保护作用 ,有效避免由于起搏器跟踪快速心房率而造成心室率过快引起的血流动力学改变 ,并能明显减轻心悸等临床症状 ,提高病人的舒适性和安全性。     

Polyspecific natural antibodies and autoantibodies secreted by human lymphocytes immortalized with Epstein-Barr virus

Recent studies have shown that autoreactive B cells and autoantibodies are present in pathological as well as in normal situations. In the present study, we immortalized human B cell lines from normal individuals and from patients with malignant or benign dysglobulinemia with Epstein-Barr virus and examined, after cloning, the autoantibody reactivities of the immunoglobulins secreted by these cells. Forty-two supernatants were analyzed by enzyme-immunoassay on a panel of 13 self and non-self antigens: trinitrobenzenesulfonic acid (TNP), DNA, L- glutamine, L-alanine, L-tyrosine (GAT), actin, myosin, tubulin, albumin, renin, spectrin, transferrin, thyroglobulin, myoglobin, peroxidase, and by immunofluorescence in tissue sections. Fourteen (33%) of the immunoglobulin-secreting cell lines were found to have an autoantibody function; seven secreted IgM, six IgA, and one IgG. The light chains were of the kappa type in 11 cases. The vast majority of these clones reacted with more than five antigens of the panel and all of them reacted with TNP. No correlation was found between a given isotype and an antibody specificity. More than half of these antibodies also reacted with cellular antigens present in tissue sections. None of the four cell lines secreting monoclonal antiviral antibodies reacted with any of the antigens of the panel. The results indicate that immunoglobulins secreted by human monoclonal lymphoid cell lines can have polyspecific autoantibody functions, similar to those found in normal human polyclonal antibodies, in human monoclonal paraproteins and in natural monoclonal antibodies synthesized by murine or rat clones obtained from physiologically normal animals.