Alteration and abnormal expression of the c-myc oncogene in human multiple myeloma

Structural alterations of the c-myc oncogene in human Burkitt's lymphoma and mouse plasmacytoma suggest that this oncogene is involved in several B cell neoplasms. The possibility of c-myc alterations in human myeloma has not been explored, probably because the low proliferative activity characteristic of this tumor impairs the propagation of representative cell lines for the performance of adequate cytogenetic studies. This report describes alterations in the c-myc locus with concomitant elevated expression of mRNA in the tumor cells of two of 37 patients with multiple myeloma. In one case, somatic cell hybrid studies revealed that the cloned rearranged DNA was entirely derived from chromosome 8, thus indicating a novel mechanism of c-myc activation different from that in Burkitt's lymphoma. Seven other patients exhibited five- to 12-fold overexpression of c-myc RNA when compared with normal marrow cells. Elevated mRNA expression in about one fourth of our patients suggests that the c-myc oncogene has a pathogenetic role in the evolution of multiple myeloma.     

Characterization of MR spectroscopic imaging of the human head and limb at 2.0 T

Using section-select and phase-encoding gradients, the authors obtained phosphorus chemical shift images of the human head and limb. Phosphorus spectra were acquired from planar sections divided into voxels as small as 7 cm3 in calf muscle and 27 cm3 in brain, with total examination times, including setup and proton locator imaging, of roughly 1 hour. Both spin-echo and free induction decay (FID) methods were employed; the FID gave superior results. Signal-to-noise ratios for the beta-adenosine triphosphate and phosphocreatine resonances were as high as 10:1 and 13:1 from volumes of 27 cm3 in brain.     

Characterization of the specificity and duration of T cell tolerance to intranasally administered peptides in mice: a role for intramolecular epitope suppression

Mucosal administration of antigens in experimental animals leads to the induction of peripheral T cell tolerance. We have previously reported that in H-2b mice, intranasal (i.n.) or oral administration of a peptide containing the immunodominant T cell epitope will down-regulate the function of CD4+ T cells reactive with Der P 1, a major target antigen in both B and T cell responses to house dust mite. In the present study we have investigated the tolerogenicity of peptides containing both dominant and subdominant determinants when given i.n. to nalve mice. Induction of tolerance by the nasally administered immunodominant peptide leads to a diminution in all T cell-derived cytokines and modulation of delayed-type hypersensitivity responses, but IgE production did not seem to be affected, furthermore the induction of T cell tolerance was stable, lasting beyond 6 months. We have also examined the specificity of intramolecular epitope suppression which is a feature of mucosal tolerance induced by nasally administered peptides and demonstrate that regulatory CD4+ T cells may exert their suppressive effect by linked recognition of epitopes on the same or neighbouring antigen-presenting cells.      

The effects of glucocorticoid therapy on glucocorticoid receptors in leukemia and lymphoma

Measurement of glucocorticoid receptors appears to be useful for selecting which patients with leukemia and lymphoma should receive glucocorticoid therapy. To determine the effect of recent or concurrent glucocorticoid therapy on the number of measured tumor glucocorticoid receptor sites, 18 patients with leukemia and lymphoma were studied. Baseline determinations of numbers of glucocorticoid receptors were performed on the malignant cells circulating in the patients' peripheral blood. Glucocorticoid therapy was then instituted consisting of dexamethasone 4 mg p.o. every 6 hr. Repeat determinations of the number of glucocorticoid receptor sites were performed within 24 hr and at various subsequent times from the start of therapy. When compared to baseline receptor numbers, 16 of 18 patients demonstrated a decrease in receptor number (median decrease 1651 sites/cell) after the start of glucocorticoid therapy. The magnitude of the change in receptor number was independent on the initial number of receptors. Our results suggest that in order accurately interpret glucocorticoid receptor numbers in patients with leukemia and lymphoma, glucocorticoid should not be administered for 3 wk prior to determinations of receptor levels.     

Screening of blood donors for idiopathic CD4+ T-lymphocytopenia

BACKGROUND: The recent recognition of idiopathic CD4+ T-lymphocytopenia (ICL) had led to concern that an unknown immunodeficiency virus may be transmissible by transfusion. STUDY DESIGN AND METHODS: To evaluate the prevalence and significance of low CD4+ values among blood donors, CD4+ data on 2030 blood donors who were negative for antibody to human immunodeficiency virus type 1 (HIV-1) were compiled. Those with CD4+ values below ICL cutoffs (< 300 CD4+ T cells/microL, or < 20% CD4+ T cells) were recalled for follow-up investigations. Serial CD4+ data on 55 homosexual men who seroconverted during prospective follow-up and data on 139 anti-HIV-1-positive blood donors initially evaluated in 1986 were reviewed as well. RESULTS: Five seronegative donors (0.25%) had absolute CD4+ counts < 300 cells per microL and/or < 20 percent. On follow-up, all five donors had immunologic findings within normal ranges, lacked HIV risk factors, and tested negative for HIV types 1 and 2 and human T-lymphotropic virus type I and II infections by antibody and polymerase chain reaction assays. Four of five donors reported transient illness shortly after their low CD4+ count donations. The median interval from HIV-1 seroconversion to an initial CD4+ value below ICL CD4+ cutoffs was 63 months for infected homosexual men. Of 139 HIV-1-infected blood donors studied 1 to 2 years after seropositive donations, 34 (24%) had CD4+ counts < 300 cells per microL and/or < 20 percent. CONCLUSION: Low CD4+ counts are rare among anti- HIV-1-negative volunteer blood donors and are generally associated with transient illnesses. If any unknown virus progresses similarly to HIV- 1, CD4+ count donor screening would be a poor surrogate for its detection.     

The Determinants of Early Nephropathy in Insulin-dependent Diabetes Mellitus: A Prospective Study Based on the Urinary Excretion of Albumin

A four-year prospective study of the factors predicting albuminuriawas carried out in 172 normotensive, insulin-dependent diabeticpatients without overt nephropathy. Urinary albumin excretionwas estimated as the urinary albumin:creatinine ratio (U_A/U_C)in an early morning sample. Multivariate analysis showed thatU_A/U_C on the return visit was positively associated with theU_A/U_C (p<0.001) and glycosylated haemoglobin (HbA₁; p<0.001) at initial examination; weaker associations were foundwith a history of hospital admission (p<0.05) and smoking(p<0.05), and with treatment of blood pressure (p<0.05).Neither initial blood pressure, heart rate, nor creatinine clearancewere significant predictors of the U_A/U_C. Two patients diedfrom coronary heart disease, both of whom had raised albuminexcretion at initial examination. Eleven (6.8 per cent) of the160 patients who were studied repeatedly developed macroalbuminuria(U_A/U_C >45.5 mg/mmol): they had a significantly higher initialU_A/U_C (p<0.005), HbA₁ (p<0.05) and a greater frequencyof retinopathy (p<0.05) than patients matched for age, sexand duration of diabetes who did not develop macroalbuminuria.Simultaneous measurements of the U_A/U_C and HbA₁ should be usedwhen screening for microalbuminuria in diabetets mellitus: patientswith a high U_A/U_C(e.g. >3.5 mg/mmol) and HbA₁ (e.g. >13 per cent) should be closely monitored even when blood pressureis normal.     

生物膜与膨体聚四氟乙烯包裹治疗动脉瘤的效果对照

目的:比较生物膜与膨体聚四氟乙烯在动脉瘤包裹的远期治疗效果。方法:实验于2004-12/2006-10年在南方医院神经外科实验室与广东冠昊动物实验中心进行。取成年健康杂种犬10只,采用显微外科技术,将双侧的颈外静脉1.5cm嫁接双侧颈总动脉缺损1.5cm制作梭形动脉瘤模型20枚。左侧10枚应用生物膜(广东冠昊生物科技有限公司产品)包裹治疗,右侧10枚应用膨体聚四氟乙烯(美国戈尔公司周围血管补片)包裹治疗。术后第1,3,6,9,12个月行彩色多普勒超声血动态观察血流动力学变化,第12个月进行数字减影血管造影检测及解剖组织学观察。结果:10只犬全部进入结果分析。①血流动力学观察:生物膜包裹侧瘤腔消失、形态上趋于正常的颈总动脉,管腔均通畅,造影剂快速通过无滞留;血流恢复为层流,频谱特征与颈总动脉一致;1个月时生物膜与瘤壁存在微小间隙,3个月后间隙完全消失,12个月时血管顺应性、弹性与颈总动脉基本相匹配。膨体聚四氟乙烯包裹侧瘤腔消失、管腔通畅6枚,腔内为层流,频谱特征与颈总动脉相似,但速度明显高于远近端颈总动脉;瘤腔轻度缩窄,内壁出现轻度波状充盈缺损,包裹片长度轻度缩短;1个月和3个月各出现2枚血栓性闭塞,经主动脉弓照影不显像。6个月内膨体聚四氟乙烯与瘤壁存在清晰微小间隙,6个月后间隙消失。②组织学观察:生物膜包裹侧外表柔软类似颈总动脉,有较多毛细血管长入但维持原形,瘤腔内膜光滑无增厚,内皮细胞无增生、脱落,未见附壁血栓;生物膜与瘤壁融合、多层次降解,降解间隙内较多新生血管、组织长入,未见炎症细胞。膨体聚四氟乙烯外表僵硬、未见周围组织长入;内膜增厚、不光滑,内皮细胞核密集、部分脱落,薄层血栓附壁;4例见胶冻状长圆柱形杂色血栓。膨体聚四氟乙烯与瘤壁嵌入无降解,未看到明显的毛细血管长入;有极少的成纤维细胞伸入,散在的淋巴细胞浸润及少量巨噬细胞。结论:生物膜具有良好的理化性能与生物相容性,其效果优于膨体聚四氟乙烯,是动脉瘤包裹治疗的理想再生医学工程材料。