Antibodies against human heat-shock protein (hsp) 60 and mycobacterial hsp65 differ in their antigen specificity and complement-activating ability.

Although complement activation appears to have an important role both in the early and late phases of atherosclerosis, the exact mechanism of the initiation of this activation is still unknown. Since injuries of the endothelial cells are known to result in increased stress-protein expression we tested the complement-activating ability of recombinant human 60 kDa heat-shock protein (hsp60). Human hsp60 was found to activate the complement system in normal human serum in a dose-dependent manner. Activation took place through the classical pathway. The lack of complement activation in agammaglobulinemic serum indicates that the classical pathway is triggered by anti-hsp60 antibodies. Hsp60 activated complement in the sera of 74 patients with coronary heart disease as well, and a strong positive correlation (r = 0.459, P < 0.0001) was found between the extent of complement activation and the level of anti-hsp60 IgG antibodies but there was no correlation to the level of anti-hsp65 IgG antibodies. Further distinction between anti-hsp60 and anti-hsp65 antibodies was obtained from competitive ELISA experiments: binding of anti-hsp60 antibodies to hsp60-coated plates was inhibited only by recombinant hsp60 and vice versa. Our present findings indicate that anti-hsp60 and anti-hsp65 antibodies are distinct, showing only partial cross-reactivity. Since complement activation plays an important role in the development of atherosclerosis and the levels of complement-activating anti-hsp60 antibodies are elevated in atherosclerosis-related diseases, our present findings may have important pathological implications.     

Interferon alpha-2c therapy of patients with chronic myelogenous leukemia: long-term results of a multicenter phase-II study

 In a prospective multicenter phase-II trial 80 patients with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) were treated with recombinant interferon (IFN)α-2c, administered subcutaneously at an absolute dose of 3.5 megaunits (MU)/day. Complete hematological remission was achieved in 29 (39%) and partial hematological remission in 26 (35%) of the 74 patients evaluable for response. Major cytogenetic responses were observed in ten (13%) and minor cytogenetic responses in 11 patients (15%). Median duration of cytogenetic response was 33 months (range, 2–90); relapses were seen in all of the 11 patients with minor and in three of the ten patients with major cytogenetic responses. Median survival estimates for pretreated (n=19) and untreated (n=58) patients were 51 months (95% confidence interval [CI], 30–72) and 77 months (95% CI, 43–111), and the survival probabilities at 5 years were 45% and 54% for the two groups, respectively. Hematological response after 3 months of treatment demonstrated a clear-cut discriminative capacity with 5-year survival probabilities of 100%, 67% and 24% for patients achieving CHR (n=6), PHR (n=34), and less than PHR (n=35), respectively. Landmark analysis at 12, 18, and 24 months after start of IFN therapy and an analysis treating time to cytogenetic response as a time-dependent covariate showed that cytogenetic response was associated with longer survival. The impact of a low-dose IFN regimen on survival in CML patients is unclear and requires further clarification by randomized clinical trials. Early hematological and cytogenetic response to IFN-α treatment identifies patients with a favorable long-term prognosis. Received: 26 October 1995 / Accepted: 3 January 1996     

Spontaneous remission in a secondary acute myelogenous leukaemia following invasive pulmonary aspergillosis

Spontaneous remission of adult acute myelogenous leukaemia (AML) represents a rare event. We report a 60-year-old female patient suffering from secondary AML M1 and severe invasive pulmonary hyalohyphomycosis highly suggestive of aspergillosis. Two months after the diagnosis of leukaemia, she achieved a spontaneous remission lasting 3 months, although neither cytostatic drugs nor corticoids were administered because of a septic condition. At the time of remission, a chronic hepatitis C virus infection and a polyclonal hypergammaglobulinaemia were present, and the patient received granulocyte colony-stimulating factor once. This report represents the first documentation of a spontaneous remission in AML following invasive pulmonary hyalohyphomycosis. Possible mechanisms of this phenomenon are discussed.     

Micro-flow nanocatalysis: synergic effect of TfOH@SPIONs and micro-flow technology as an efficient and robust catalytic system for the synthesis of plasticizers

The combination of continuous flow technology with immobilizing of only 0.13 mol% of triflic acid (TfOH) on silica-encapsulated superparamagnetic iron oxide nanoparticles (SPIONs) under solvent-free conditions successfully provided a powerful, efficient, and eco-friendly route for the synthesis of plasticizers. The turnover frequency value in micro-flow conditions varied in the range of 948.7 to 7384.6 h⁻¹ compared to 403.8 to 3099 h⁻¹ for in-flask. This technique works efficiently, encouraging future applications of micro-flow nano-catalysis in green chemistry.

The combination of continuous flow technology with nanocatalyst for the synthesis of plasticizers.

The investigation of powerful and less hazardous chemical catalysts has become a priority in developing sustainable organic transformations.^1,2 Triflic acid (TfOH), as a versatile Brønsted acid catalyst, has been used widespread in organic transformations.^3–11 However, the difficulties in handling and transportation of TfOH associated with its highly corrosive nature, restrict its industrial applications.¹² Moreover, the recovery of TfOH from the reaction mixture leads to the formation of large amounts of waste.^12,13 To solve these problems, immobilization of TfOH onto an inorganic matrix as a heterogeneous catalyst is an alternative, which features easy-handling, low toxicity, superior stability, etc. Despite these advantages, the obtained catalyst still suffers several drawbacks, such as low surface area, the monotonous recycling by filtration, and loss of catalyst during recovery.^14–18 Recently, a new TfOH catalyst based on silica-coated magnetic nanoparticles was reported by Zhang and co-workers and showed high efficiency, good recyclability, and reusability in the transformation of aldehydes or ketones into their corresponding gem-dihydroperoxides.¹⁹ Therefore, extension of investigation on this superacid generation, which could produce more fine chemicals and further increase the efficiency via combining new technology, is in high demand. Nowadays, there is a growing interest in developing of micro-flow technology for various organic transformations.^20–24 This technology allows a directed reactant flux through an immobilized catalyst, making it attractive by enhancing mass- and heat-transfer characteristics via low hold-up volumes. Micro-flow technology has also an excellent thermal transport capability, as well as the ability to efficiently optimize reaction conditions by controlling the residence time.^25–28 Moreover, the yields of reactions performed in the microreactor at a very short residence time, even for scaled up reactions, are much higher than those obtained via conventional stirring.²⁹ Therefore, integrating the advances of micro-flow chemistry into the TfOH heterogeneous catalyst would bring new features, such as higher yields and efficient optimization, in addition to the good recyclability and reusability. Micro-flow nanocatalysts could serve as a new and practical technique for overcoming of the problems mentioned above.To this end, we prepared TfOH functionalized silica-encapsulated superparamagnetic iron oxide nanoparticles (TfOH@SPIONs) and tested their efficiency in synthesizing plasticizers with micro-flow techniques. Plasticizers are an essential ingredient for the producing of macromolecule materials used widely by polymer industries.^30,31 A variety of modified catalytic processes have been performed; from traditional catalysts, such as sulfuric acid³² and titanate,³³ to more modern ionic liquids³⁴ for the synthesis of plasticizer esters. Although these methods are valuable, most of them require hours of reflux, utilizing expensive or corrosive catalysts, tedious work-up, difficult recovery, and easy deactivation with consumption of energy. Therefore, implementation of eco-friendly and straightforward chemical methods remains a particularly interesting task.The aforementioned explanations and our recent investigations on the micro-flow nano-catalyst technology,³⁵ encouraged us to develop the ultimate green synthesis, very practical, and straightforward protocol for the synthesis of plasticizer esters via the first combination of TfOH@SPION with micro-flow technique.     

Healthy twin live-birth after ionophore treatment in a case of theophylline-resistant Kartagener syndrome

Purpose

To evaluate whether it is a feasible option to target the oocyte (with Ca²⁺-ionophore) in case that sperm motility cannot be restored in Kartagener syndrome.

Methods

A case of a male Kartagener syndrome with exclusively immotile spermatozoa that did not react to the dimethylxanthine theophylline. Thus, half of the associated oocytes were treated for 15 min with the ready-to-use- ionophore CultActive immediately after ICSI whereas the other 50 % were injected with routine ICSI without artificial oocyte activation. Rates of fertilization, blastulation, pregnancy and live birth were evaluated.

Results

Fertilization check revealed that none of the conventionally injected but 4/6 (66.7 %) of the artificially activated oocytes showed two pronuclei. Three embryos were of good and one of fair quality. Corresponding blastocyst formation rate was 3 out of 4 (75 %). A double embryo transfer led to a healthy twin birth in the 34th week of gestation (two boys with a birth weight of 1724 g and 2199 g).

Conclusions

This case indicates that Ca²⁺-ionophore treatment in cycles from theophylline-resistant Kartagener syndrome patients is a feasible option. The future will show if routine application of A23187 in Kartagener or primary cilia dyskinesis patients will be of benefit.     

Planar embryos have poor prognosis in terms of blastocyst formation and implantation

Normally, day-2 embryos show a crosswise arrangement of four cells with three blastomeres lying side by side. Cleavage anomalies include embryos that are characterized by a particular planar constellation of four blastomeres with presumed incomplete cleavage. Since little is known on the developmental fate of such conceptuses, within a 10-month period all consecutive patients were screened for day-2 planar embryos. A total of 64/2070 embryos with suboptimal blastomere configuration were detected (3.1%). In conventional IVF, planar embryos were significantly less frequent (0.7%) as compared with intracytoplasmic sperm injection (2.8%; P < 0.05) and cases of testicular sperm extraction (5.4%; P < 0.01). Interestingly, embryos with a cleavage anomaly showed better morphology both on day 2 (P < 0.005) and day 3 (P < 0.001). In contrast, blastocyst formation (P < 0.001) and blastocyst quality (P = NS) was higher in tetrahedral embryos. There was a significant increase in implantation rate if tetrahedral embryos could be transferred compared with when planar embryos had to be transferred (P < 0.01). It may be postulated that, in planar embryos, the mitotic spindle might have been affected, e.g. sperm centrosome composition or function, which in turn might have led to the observed cleavage anomaly.Normally, day-2 embryos show a crosswise arrangement of four cells with three blastomeres lying side by side. Cleavage anomalies include more planar embryos that are characterized by a particular flat constellation of four blastomeres with presumed premature cleavage (like a tetrafoliate clover). Since little is known on the developmental fate of such embryos within a 10-month study period, all consecutive patients were screened for the presence of day-2 planar embryos (study group). A total of 64 (out of 2070) embryos with abnormal blastomere configuration were detected (3.1%). Interestingly, in conventional IVF (0.7%), the presence of planar embryos was significantly less frequent as compared with intracytoplasmic sperm injection (2.8%; P < 0.05) and cases of testicular biopsy (5.4%; P < 0.01). Embryos from the study group showed better morphology both on day 2 (P < 0.005) and day 3 (P < 0.001). In contrast, blastocyst formation (survival to day 5 of preimplantation development) was higher in the normally cleaved control group (P < 0.001) and so was blastocyst quality; however, the latter parameter did not reach level of significance. This was also reflected in a significantly higher implantation rate in the control group (P < 0.01). Based on present data, it may be postulated that, in planar embryos, the mitotic spindle (which involves the sperm centrosome) might have been affected, which in turn might have led to an incomplete cleavage.     

拉米夫定与恩替卡韦治疗藏族慢性乙型肝炎患者的临床疗效和安全性对比

目的 探讨拉米夫定与恩替卡韦治疗藏族慢性乙型肝炎患者的临床疗效和安全性.方法 采用随机数字表法,将符合纳入标准的114例藏族慢性乙型肝炎患者随机分为两组:恩替卡韦组(ETV组,n=57)和拉米夫定(LVD组,n=57).恩替卡韦组给予恩替卡韦片0.5 mg,口服,1次/d;拉米夫定组给与拉米夫定片100 mg,口服,1次/d,两组分别治疗48周.于治疗前及治疗12、24、48周时点测定两组的ALT和HBV DNA值,记录ALT复常、HBV DNA转阴、HBeAg转阴及血清学转换的患者例数以及治疗过程中不良事件的发生情况.结果 与治疗前比较,两组患者治疗12、24、48周时ALT、HBV DNA定量值均下降;与LVD组比较,治疗12、24周时ETV组的ALT、HBV DNA定量值下降,ALT复常率、HBV DNA转阴率升高,差异有统计学意义(P<0.05).两组患者在治疗过程中均未发生严重不良反应事件.结论 拉米夫定与恩替卡韦治疗藏族慢性乙型肝炎患者安全、有效,但拉米夫定耐药性高,恩替卡韦在恢复肝功能及降低HBV复制的效果优于拉米夫定.