淋巴结血管内T细胞淋巴瘤1例报道及文献复习

目的　探讨血管内淋巴瘤 (IVL)的临床病理特征。方法　对 1例腹股沟淋巴结IVL临床、病理组织学及免疫表型进行观察分析并复习文献。结果　男性 31岁 ,不明原因高热伴消瘦 5 0天 ,右腹股沟直径 1cm淋巴结 1枚 ,B超示肝脏轻度增大 ,血LDH明显升高伴ESR及转氨酶轻度升高 ,外周血WBC 3 3× 10 7/L ,骨髓像、多种病原及各肿瘤相关抗原检测均无异常。病理活检 :腹股沟淋巴结大部分破坏 ,代之以大量扩张的中小血管 ,腔内充满大量异型淋巴样细胞 ,局部伴管壁、管周浸润并累及结外脂肪组织。瘤细胞免疫表型CD4 5、CD4 5RO、CD3阳性 ,CK、CD6 8、CD79α、CD2 0均阴性 ,血管壁及内皮细胞CD31、CD34阳性。行CHOP化疗后症状缓解 ,现仍在随访中。结论　IVL是一罕见的非霍奇金淋巴瘤 ,好发于中枢神经系统及皮肤 ,其他部位少见 ,绝大数为B细胞型 ,T型罕见 ,以浅表淋巴结活检确诊者尚无报道。临床表现有一定提示性 ,确诊靠组织病理学检查 ,部分病例对化疗敏感 ,但多数病例预后差     

Rapid non-genomic inhibitory effects of glucocorticoids on human neutrophil degranulation

Background: Glucocorticoids acting as anti-inflammatory or immunosuppressive drugs have been shown to exert most of their effects genomically. Recent findings suggest that non-genomic activity might be relatively more important in mediating the therapeutic effects of high-dose pulsed glucocorticoid. However, few non-genomic anti-inflammatory effects were reported, much less non-genomic mechanisms.Objective: This study was performed to investigate the nongenomic effects of glucocorticoids on human neutrophil degranulation.Methods: Purified human neutrophils were pretreated with 6 -methylprednisolone or hydrocortisone for 5 min, and then primed with N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10^–6 M) or phorbol myristate acetate (PMA) (50 ng/ml) in the presence of cytochalasin B. The release of two markers of neutrophil granules, lactoferrin and myeloperoxidase, was measured by ELISA and enzymology methods respectively.Results: Both 6 -methylprednisolone (10^–5–10^–4 M) and hydrocortisone (10^–4 M) showed significant inhibitory effects on neutrophil degranulation within 5 min after fMLP administration. For PMA stimulated degranulation, 6 -methylprednisolone (10^–4 M) showed significant inhibitory effects (p < 0.01), while hydrocortisone (10^–4 M) only showed an inhibitory tendency (P > 0.05). Neither RU486 (10^–5 M) nor cycloheximide (10^–4 M) could alter the inhibitory effects of glucocorticoids.Conclusion: Our results demonstrate that megadoses of glucocorticoids exert rapid inhibitory effects on human neutrophil degranulation at the cellular level via a new mechanism that is independent of corticosteroid type II receptor occupation or protein synthesis. We infer that these effects may be very important when glucocorticoids act as anti-inflammatory drugs during pulse therapy.Received 20 May 2004; returned for revision 21 July 2004; accepted by M.J. Parnham 23 September 2004L. Liu and Y. X. Wang contributed equally to this work.     

Changes in bone turnover during tibolone treatment

OBJECTIVES: An open study was carried out to evaluate changes in bone remodeling markers such as N-telopeptide (NTx), tartrate-resistant acid phosphatase (TRAP), total alkaline phosphatase (TAP), and bone alkaline phosphatase (BAP) during a 1-year continuous tibolone treatment in postmenopausal women. MATERIAL AND METHODS: Thirty-six postmenopausal women were recruited for receiving tibolone 2.5 mg per day for 1 year. Densitometry and determination of biochemical markers of bone metabolism in serum and urine were performed at 1, 3, 6, and 12 months. RESULTS: Comparing baseline with 12 month's values, BAP and all resorption markers decreased significantly. NTx began to decrease since the initiation of the treatment (baseline: 74.4 +/- 5.3; 1 month: 57.5 +/- 4.2; 12 months: 36.6 +/- 2.8). BAP increased at the first month (baseline: 37.3 +/- 2.1; 1 month: 42.6 +/- 3.0) but diminished in the following months (12 months: 23.1 +/- 1.5). TAP started to decrease significantly only after 6 months of treatment (baseline: 37.3 +/- 2.1; 12 months: 31.4 +/- 2.3) and TRAP after 3 months (baseline: 9.8 +/- 0.4; 6 months: 9.1 +/- 0.5; 12 months: 8.2 +/- 0.4). Normal bone mineral density at distal and ultradistal forearm was maintained during the 1-year treatment (baseline: 0.42 +/- 0.01; 12 months: 0.42 +/- 0.01 and baseline: 0.33 +/- 0.01; 12 months: 0.33 +/- 0.01, respectively). CONCLUSION: The use of tibolone 2.5 mg per day diminished progressively and significantly bone resorption and formation markers during 1-year treatment period.     

Neonatal sepsis in the neonatal intensive care unit: characteristics of early versus late onset.

Neonatal sepsis is a major cause of death in newborns despite sophisticated neonatal intensive care. This retrospective study reviewed the clinical characteristics of cases of culture-proven sepsis in a neonatal intensive care unit from January 1992 to December 2001. Patients were divided into those with onset of sepsis in the first 7 days of life (early-onset group) and those with onset after the seventh day of life (late-onset group). A total of 270 cases with 325 episodes of sepsis and 353 isolated pathogens were identified and included in the study. The male-to-female ratio was 1.4. The majority of cases of sepsis occurred in low birth weight (75.9%) and premature babies (76.7%). Late onset occurred in 71.9% of cases. Patients with late onset had a lower mortality rate than those with early onset (11.3% vs 28.9%). Coagulase-negative staphylococci (20.1%) was the most common organism isolated, but infection with Pseudomonas aeruginosa was associated with the highest morality rate (55.0%). Late-onset sepsis was significantly more common in very low birth weight and premature infants. The most frequently encountered pathogens in the early-onset group were group B streptococci (GBS) and Escherichia coli, while in the late-onset group, the organisms were coagulase-negative staphylococci and Enterobacteriaceae, including E. coli, Klebsiella pneumoniae, and Acinetobacter baumannii. GBS infection resulted in the highest mortality when the onset of sepsis was within the first 24 hours of life.     

CD4 lymphocytes in the blood of HIV(+) individuals migrate rapidly to lymph nodes and bone marrow: support for homing theory of CD4 cell depletion

Recent studies have provided evidence that macrophages from Th1-prone mouse strains respond with an M1 profile, and macrophages from Th2-prone mouse strains respond with an M2 profile, characterized by the dominant production of NO or TGF-beta 1, respectively. We have shown that peritoneal macrophages from IL-12p40 gene knockout mice have a bias toward the M2 profile, spontaneously secreting large amounts of TGF-beta 1 and responding to rIFN-gamma with weak NO production. Moreover, IL-12p40KO macrophages are more permissive to Trypanosoma cruzi replication than their wild-type littermate cells. Prolonged incubation with rIL-12 fails to reverse the M2 polarization of IL-12p40KO macrophages. However, TGF-beta 1 is directly implicated in sustaining the M2 profile because its inhibition increases NO release from IL-12p40KO macrophages. IFN-gamma deficiency is apparently not the reason for TGF-beta 1 up-regulation, because rIFN-gamma KO macrophages produce normal amounts of this cytokine. These findings raise the possibility that IL-12 has a central role in driving macrophage polarization, regulating their intrinsic ability to respond against intracellular parasites.     

大鼠脊髓损伤后NGF及其受体TrkA在运动神经元及神经胶质细胞表达的变化

为探讨脊髓损伤后运动神经元及神经胶质细胞内神经生长因子(NGF)及其高亲和力受体(TrkA)表达的变化,用改良Allen重击法损伤SCI组动物T12脊髓,按伤后存活时间再将动物分为脊髓损1 d组、2 d组和5 d组。各组动物的脊髓切片经ABC法免疫组织化学染色,用光镜观察TrkA及NGF在脊髓前角运动神经元表达的变化和胶质纤维酸性蛋白(GFAP)及NGF免疫反应阳性胶质细胞的反应性增生程度,并进行图像分析。结果显示:脊髓损伤后前角运动神经元TrkA及NGF的表达随脊髓损伤后动物存活时间的延长逐渐上调;脊髓白质和灰质内尤其是皮质脊髓束内GFAP及NGF阳性胶质细胞明显增生;与此同时,室管膜细胞内亦可见明显的NGF免疫反应产物。上述结果表明,脊髓损伤可刺激脊髓前角运动神经元表达TrkA及NGF,通过自分泌维持受损神经元的存活;损伤部位反应性增生的胶质细胞亦可产生NGF,通过旁分泌作用于脊髓前角运动神经元或皮质脊髓束的轴突末梢,以维持运动神经元的存活及促进皮质脊髓束的再生;适时补充外源性神经营养素或改变损伤局部的微环境将有利于受损脊髓的修复和再生。     

Dominant mutations affecting both sporulation and sterigmatocystin biosynthesis in Aspergillus nidulans

The initiation of conidiophore development in the filamentous fungus Aspergillus nidulans is a complex process requiring the activities of several genes including fluG, flbA, flbB, flbC, flbD, and flbE. Recessive mutations in any one of these genes result in greatly reduced expression of the brlA developmental regulatory gene and a colony morphology described as fluffy. These fluffy mutants have somewhat diverse phenotypes but generally grow as undifferentiated masses of vegetative hyphae to form large cotton-like colonies. In this paper we describe a genetic screen to identify dominant mutations resulting in similar fluffy colony morphologies. We have identified 36 dominant fluffy mutant strains and shown that 29 of these mutants have greatly reduced brlA expression as compared to wild-type. In addition, we have found that 19 of these mutants are not only developmentally altered but also fail to produce the toxic, carcinogenic, secondary metabolite sterigmatocystin. At least three of the mutants isolated result from dominant activating mutations in fadA which encodes the Gα subunit of a heterotrimeric G-protein. Another of the mutants results from a dominant interfering mutation in brlA. We discuss the approaches taken to characterize these potentially important regulators of growth, development and secondary metabolism. Received: 13 February / 28 May 1997     

Innovations in curriculum design: A multi-disciplinary approach to teaching statistics to undergraduate medical students

Background  

Statistics is relevant to students and practitioners in medicine and health sciences and is increasingly taught as part of the medical curriculum. However, it is common for students to dislike and under-perform in statistics. We sought to address these issues by redesigning the way that statistics is taught.