Characterization of Thy-1 (CDw90) expression in CD34+ acute leukemia

Thy-1 (CDw90) is a phosphatidylinositol-anchored cell surface molecule which, when coexpressed with CD34 in normal human bone marrow, identifies a population of immature cells that includes putative hematopoietic stem cells. To date, the characterization of Thy-1 expression has been confined largely to normal tissues and cell lines. In this study, we evaluated the frequency and intensity of Thy-1 expression as defined by reactivity with the anti-Thy-1 antibody 5E10 in 38 cases of CD34+ acute leukemia (21 acute myelogenous leukemia [AML], 8 chronic myelogenous leukemia [CML] in blast crisis, and 9 acute lymphoblastic leukemia [ALL]). In 34 of 38 cases (89%) the CD34+ cells lacked expression of the Thy-1 antigen. High-density Thy-1 expression was found in 1 case of CML in lymphoid blast crisis, and low- density Thy-1 expression was identified on a portion of the leukemic cells in 2 cases of AML with myelodysplastic features, and 1 case of CML in myeloid blast crisis, suggesting a possible correlation between Thy-1 expression and certain instances of stem cell disorders such as CML and AML with dysplastic features. In contrast, the dissociation of Thy-1 and CD34 expression in the majority of acute leukemias studied suggests that the development of these leukemias occurs at a later stage than the hematopoietic stem cell. Characterization of Thy-1 expression in acute leukemia may eventually provide insights into the origin of the disease. In addition, separation of leukemic blasts from normal stem cells based on Thy-1 expression may prove useful in assessing residual disease, as well as in excluding leukemic blasts from stem cell preparations destined for autologous bone marrow or peripheral stem cell transplantation.     

A survey of hepatitis B surface antigen-positive blood donors: degree of understanding and action taken after notification

All blood donors in the United States are tested for hepatitis B surface antigen (HBsAg) upon donation; if the test result is positive, the primary method of notification is by letter. To assess the effectiveness of this notification methods in stimulating HBsAg-positive donors to seek medical care and take preventive measures, 54 donors who tested HBsAg-positive on donation at the American Red Cross Blood Services. Atlanta Region, from January 1987 to July 1989 were interviewed. Thirty-nine donors (72%) had sought medical care after notification; the only motivating factor was that the letter told the donor to consult with his or her physician. Compared with donors who did not seek medical care, donors who did so were more likely to understand that the blood test was abnormal or that they were infected, and they were more likely to understand how hepatitis B virus is transmitted and that a vaccine is available. The differences were not significant, however. Of those donors who sought medical care, less than half received appropriate recommendations for protection of contacts, and of those who did, only one-third received prophylaxis. In-person and telephone interviews with donors, revision of the notification letter, and hepatitis B education programs targeted at medical care providers are suggested.     

铅对肾上腺皮质细胞线粒体的氧化损伤

目的】 研究铅对肾上腺皮质细胞氧化应激和线粒体功能的 影响,为了解其肾上腺皮质毒作用机制提供依据。【方法】 原代分离培养豚鼠肾上腺皮质 细胞,以0、6.25、12.5、25、50、100 μmol/L醋酸铅(PbAc)处理细胞,观察PbAc诱导肾 上腺皮质细胞活性氧(ROS)产生和线粒体损伤作用。ROS检测采用荧光分光光度法,线粒体膜 电位(MMP)和细胞存活状态采用Rh123和PI双标记、流式细胞术检测,细胞ATP水平采用化学 发光法测定。【结果】 PbAc染毒后肾上腺皮质细胞ROS形成水平随剂量增加而增加,具有剂 量效应关系[y=4.16+10.21×1g(x+1),P<0.01,R2=0.64 1］;线 粒体膜电位呈剂量依赖性降低,Rh123的平均荧光强度(MFI)在6.25～100 μmol/L各剂量组 依次为1.01,0.94,0.96,0.95和0.91,与对照组(1.35)比较具有显著性差异(P<0 .01);染毒后细胞死亡率轻度增加,与对照组(1.02%)比较,50 μmol/L和100 μmol/L的 PbAc组分别为3.16%和3.40%,差异具有显著性(P<0.05);ATP水平降低与PbAc剂量之 间存在剂量效应关系[y=212965.7-51592.5×1g(x+1),P<0.01,R2= 0.568］,剂量和时间对ATP水平的影响呈协同抑制作用(P<0.01)。【结论】 线粒体 氧化应激介导肾上腺皮质细胞毒性可能是PbAc毒作用机制之一,线粒体损伤是铅致肾上腺皮 质毒作用的早期细胞和分子事件。     

Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke,seizures and sensorimotor gating deficit

Background and purpose:

Abnormal glutamatergic activity is implicated in neurologic and neuropsychiatric disorders. Selective glutamate receptor antagonists were highly effective in animal models of stroke and seizures but failed in further clinical development because of serious side effects, including an almost complete set of symptoms of schizophrenia. Therefore, the novel polyvalent glutamatergic agent 3,5-dibromo-L-phenylalanine (3,5-DBr-L-Phe) was studied in rat models of stroke, seizures and sensorimotor gating deficit.

Experimental approach:

3,5-DBr-L-Phe was administered intraperitoneally as three boluses after intracerebral injection of endothelin-1 (ET-1) adjacent to the middle cerebral artery to cause brain injury (a model of stroke). 3,5-DBr-L-Phe was also given as a single bolus prior to pentylenetetrazole (PTZ) injection to induce seizures or prior to the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) to cause disruption of prepulse inhibition (PPI) of startle (sensorimotor gating deficit).

Key results:

Brain damage caused by ET-1 was reduced by 52%, which is comparable with the effects of MK-801 in this model as reported by others. 3,5-DBr-L-Phe significantly reduced seizures induced by PTZ without the significant effects on arterial blood pressure and heart rate normally caused by NMDA antagonists. 3,5-DBr-L-Phe prevented the disruption of PPI measured 3 days after the administration of ET-1. 3,5-DBr-L-Phe also eliminated sensorimotor gating deficit caused by MK-801.

Conclusion and implications:

The pharmacological profile of 3,5-DBr-L-Phe might be beneficial not only for developing a therapy for the neurological and cognitive symptoms of stroke and seizures but also for some neuropsychiatric disorders.     

Effect of micronized fenofibrate on microvascular complications of type 2 diabetes: a systematic review

Objective: Micronized fenofibrate prevents the progression of microvascular complications in type 2 diabetes, but no systematic review has summarized these effects. Therefore, we performed a systematic review to investigate the effects of micronized fenofibrate on type 2 diabetes-related microvascular complications.

Research design and methods: The PubMed database was systematically searched for trials in English language published between January 1990 and November 2015 that examined the effects of fenofibrate on microvascular complications in patients with type 2 diabetes.

Results: Thirteen trials of the 290 clinical studies reviewed met the inclusion criteria. Fenofibrate significantly slowed the progression of early diabetic retinopathy by 30 to 40% within 4 to 5 years in patients with type 2 diabetes mellitus and pre-existing retinopathy at baseline. Fenofibrate also consistently reduced the progression of urinary albumin excretion in the trials studied. One large study demonstrated a significant effect (47% reduction) of the drug on diabetes-related minor amputations.

Conclusions: The available evidence supports the adjunctive early use of fenofibrate in type 2 diabetes mellitus for the prevention of microvascular complications, particularly in individuals presenting with the first signs of the complication and during the initial stages of the disease.