The end adjusts the means: Heterochromatin remodelling during terminal cell differentiation

All cells that constitute mature tissues in an eukaryotic organism undergo a multistep process of cell differentiation. At the terminal stage of this process, cells either cease to proliferate forever or rest for a very long period of time. During terminal differentiation, most of the genes that are required for cell ‘housekeeping’ functions, such as proto-oncogenes and other cell-cycle and cell proliferation genes, become stably repressed. At the same time, nuclear chromatin undergoes dramatic morphological and structural changes at the higher-order levels of chromatin organization. These changes involve both constitutively inactive chromosomal regions (constitutive heterochromatin) and the formerly active genes that become silenced and structurally modified to form facultative heterochromatin. Here we approach terminal cell differentiation as a unique system that allows us to combine biochemical, ultrastructural and molecular genetic techniques to study the relationship between the hierarchy of chromatin higher-order structures in the nucleus and its function(s) in dynamic packing of genetic material in a form that remains amenable to regulation of gene activity and other DNA-dependent cellular processes.     

糖蛋白(MUC1与MUC7)基因在膀胱移行细胞癌的表达研究

目的 探讨糖蛋白MUC1与MUC7基因在膀胱移行细胞癌（BTCC）组织及细胞株中的表达及意义。方法 采用MUC1与MUC7特异性巢式逆转录-聚合酶链反应（RT—PCR）对分离的4种组织标本及3种细胞株的mRNA样本进行检测。结果 所有4种组织标本及3种膀胱癌细胞株的MUC1基因表达均为阳性。MUC7基因表达仅见于3种膀胱癌细胞株和侵袭性移行细胞癌标本。半定量结果显示MUC1 mRNA基因表达在正常膀胱黏膜同腺性膀胱炎及各期膀胱癌之间差异有统计学意义（P〈0．05）。浅表性膀胱癌与侵袭性膀胱癌之间差异有统计学意义（P〈0．05）。不同细胞系BIU-87与T24之间表达差异无统计学意义（P〉0．05），耐药细胞株BIU-87／A同敏感细胞株BIU-87与T24之间表达差异有统计学意义（P〈0．05）。MUC7 mRNA基因表达在3种细胞株及侵袭性膀胱癌组织之间差异无统计学意义（P〉0．05）。结论 MUC1基因的上调表达与MUC7基因的差异性表达可能影响膀胱癌细胞的生物学行为，导致相应的临床后果-恶性转变、侵袭转移、耐药。MUC7基因表达是尿路上皮恶性侵袭性转化的开始。     

大鼠壁胸膜通透性的电镜观察

目的观察大鼠壁胸膜的通透性，胸膜腔内物质的吸收途径。方法向大鼠胸膜腔内注射示踪剂，应用光镜、透射电镜方法观察壁胸膜的物质吸收途径以及壁胸膜间皮的形态变化。结果壁胸膜表面覆盖一层连续的间皮细胞，间皮细胞按形态可分为立方形和扁平形问皮细胞，立方形间皮细胞下的结缔组织内存在大量的毛细淋巴管。由毛细淋巴管内皮细胞突起穿过间皮下结缔组织与问皮细胞相连接而形成的间皮孔，是物质吸收的主要途径。结论壁胸膜通过三种途径吸收物质：①间皮孔的吸收作用；②问皮细胞的吞噬作用；③通过问皮细胞间裂隙吸收。     

灌注液对糖尿病玻璃体切割手术中角膜内皮的影响

目的 评价不同灌注液对糖尿病玻璃体切割手术中角膜内皮细胞的影响。方法 对30例术中应用BSS或BSSPlus的糖尿病玻璃体切割手术眼的角膜内皮细胞密度和细胞面积变异系数进行前瞻性研究．结果 无囊膜组中应用BSSPlus的玻切手术眼角膜内皮细胞密度、细胞面积变异系数与应用BSS的手术眼之间存在明显差异，在有囊膜组中二者之间无明显差异。结论 对于囊膜不完整的糖尿病患者玻切手术中使用BSSPlus可减轻手术对角膜内皮细胞的损害。     

枸杞多糖对氧化损伤大鼠晶状体上皮细胞凋亡的调控

目的 :研究枸杞多糖 (lyciumbarbarumpolysaccha rides,LBP)对实验性晶状体氧化损伤所致晶状体上皮细胞(lensepithelialcell,LEC)凋亡的影响。方法 :复制大鼠晶状体LEC凋亡模型 ,将 2 4只透明晶状体随机分为 4组 ,空白组、H2 O2 组、白内停组、枸杞多糖组。枸杞多糖组加入终浓度为1g/L的枸杞多糖共同孵育 2 4h ,采用TUNEL法检测LEC凋亡率 ,用透射电子显微镜观察LEC超微结构改变。结果H2 O2 组LEC凋亡率 (92 .0± 2 .5 5 )显著高于空白组 (3.5± 1.84 ) ,(t=6 2 .97,P <0 .0 1) ;枸杞多糖组LEC凋亡率 (16 .6±8.11)与白内停组比较 ,差异有非常显著性 (t=15 .5 0 ,P <0 .0 1)。透射电镜观察 ,H2 O2 组胞浆明显浓缩 ,核内染色质凝聚或成块 ,枸杞多糖组多数LEC形态改变轻微 ,表现为胞浆基质密度轻度升高 ,部分线粒体水肿 ,细胞间间隙增宽。结论 :枸杞多糖可明显抑制LEC凋亡 ,从祖国医药中寻求防治白内障的有效药物具有广阔前景。     

Long-Term Depression in Rat Cerebellum Requires both NO Synthase and NO-sensitive Guanylyl Cyclase

Long-term depression (LTD) of synaptic transmission between parallel fibres and Purkinje cells is a well-known example of synaptic plasticity taking place in the cerebellum. Nitric oxide (NO) has been implicated in synaptic plasticity in other brain areas, but its function in cerebellar LTD is controversial. Even when an involvement is suggested, the NO signal transduction pathway is unclear. One candidate is the cyclic GMP-synthesizing enzyme, soluble guanylyl cyclase, whose activity in the brain and elsewhere is powerfully stimulated by NO. By recording intracellularly from Purkinje cells in cerebellar slices, we demonstrate that blockade of NO synthase completely inhibits LTD induced by pairing parallel fibre stimulation with postsynaptic Ca²⁺ spike firing. LTD was also blocked by intracellular application of 1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxalin-1-one, a recently identified potent and selective inhibitor of soluble guanylyl cyclase. These findings indicate that soluble guanylyl cyclase is required for cerebellar LTD and suggest that this enzyme, located within Purkinje cells, transduces the NO signal in this form of synaptic plasticity.     

Satisfactory Remission Achieved by PUVA Therapy in Langerhans Cell Hisiocytosis in an Elderly Patient

Langerhans cell histiocytosis is currently regarded as a reactive proliferative process of Langerhans cells rather than a malignancy. The disease is characterized by Langerhans cell infiltration of skin, lung, bone and other organs. We report a 74-year-old man with Langerhans cell histiocytosis who had generalized hemorrhagic and crusted papules. He also had diabetes insipidus. Because he did not have any severe constitutional symptoms or failure of vital organs, we applied topical PUVA treatment to his skin lesions, which responded well to the therapy. Diabetes insipidus, however, remained, in spite of X ray radiotherapy for the pituiary lesion.     

Absence of structural alterations of the multidrug resistance genes in transitional cell carcinoma

Summary Tumor DNA from 27 patients with treated or untreated transitional cell carcinomas of the urinary tract was screened for genomic alterations of the multidrug resistance genes in order to determine whether structural changes of these genes are important in primary urothelial tumors. None of the tumors showed evidence of amplification or rearrangements of either mdr1 or mdr2. The lack of amplification or rearrangements observed in these tumors suggests that structural alterations of the mdr1 and mdr2 genes are not important mediators of drug resistance in TCC.Supported in part by grant CA-34775 from the National Institutes of Health and by a grant from the Heckscher Foundation for ChildrenDr. Klein is a fellow of the American Cancer Society     

Cytochemical Redistribution of 5'-Nucleotidase in the Developing Cat Visual Cortex

The adenosine-producing ectoenzyme 5'-nucleotidase has recently been shown to undergo a marked redistribution during development of the cat visual cortex and to be involved in the remodelling of ocular dominance columns (Schoen et al., J. Comp. Neurol. , 296 , 379 – 392, 1990). Using an enzyme-cytochemical technique, we now investigate the developmental redistribution of 5'-nucleotidase activity in area 17 of kittens at the ultrastructural level. Between postnatal days 35 and 42, when 5'-nucleotidase is concentrated in layer IV, enzyme reaction product occupies the clefts of asymmetrical synapses within the neuropil. During later development (9th and 13th postnatal weeks), when 5'-nucleotidase spreads over all cortical laminae, the enzyme disappears from its synaptic localization and becomes increasingly associated with astrocytic membranes. The transient appearance of 5'-nucleotidase at synapses parallels the time-course and laminar profile of the synaptic remodelling which takes place during the critical period of visual cortex development. This suggests that synapse-bound 5'-nucleotidase activity plays a role in synaptic malleability, whereas its later association with glial profiles is likely to reflect other functions of the enzyme.     

Chronic renal failure and its treatment in tuberous sclerosis

BACKGROUND.: Chronic renal failure is rare in tuberous sclerosis, but itsprecise frequency is not known and treatment modalities havenot been evaluated. METHODS.: A questionnaire was addressed to the 260 French dialysis centresand the characteristics of 65 patients with tuberous sclerosisand chronic renal failure were analysed. RESULTS.: In France the approximate prevalence of tuberous sclerosis withend-stage renal failure is 0.7 cases per million and that ofend-stage renal failure in tuberous sclerosis 1 per 100. Tuberoussclerosis with chronic renal failure was more frequent in females(63.1%) and was diagnosed at a mean age of 29 years. Renal impairmentwas the first manifestation of tuberous sclerosis in about halfthe cases. Renal tumours were frequent, with angiomyolipomasin 15 cases (23.1%), cysts in 12 cases (18.5%), and both in35 cases (53.8%). Malignancies were associated in nine cases(13.8%). Nephrectomy was done before dialysis in 21 cases (32.3%),and after the start of dialysis in six cases (9.2%). All butone of the 48 patients with end-stage renal failure were treatedby dialysis; 20 were transplanted, with good results. CONCLUSIONS.: Tuberous sclerosis with end-stage renal failure is rare. Thesepatients require dialysis and renal transplantation, but werecommend binephrectomy after starting dialysis and before transplantation,given the risk of cancer and bleeding related to angiomyolipomas.