Current therapy of retrolental fibroplasia. Retinopathy of prematurity

Retrolental fibroplasia, frequently referred to now as the "retinopathy of prematurity," has shown an increased incidence in recent years. This is apparently due to advances in neonatal care, which have resulted in a four- to five-fold improvement in the survival of the extremely low birthweight infants and it is these infants who are at the highest risk of developing retrolental fibroplasia. The use of large supplements of vitamin E, a known antioxidant, is discussed along with other forms of therapy.     

Antitumor effects of a nonsteroidal aromatase inhibitor (CGS 16949A) on 7, 12-dimethylbenz[alpha]anthracene-induced mammary tumors in rats.

The effects of a nonsteroidal aromatase inhibitor, CGS 16949A, on female Sprague-Dawley (SD) rats with 7, 12-dimethylbenz[alpha]anthracene (DMBA)-induced mammary cancers were examined in relation to estrogen receptors (ER). Rat tumor sizes in each treated group were significantly smaller (P less than 0.05) and rat body weights in most treated groups were significantly increased (P less than 0.05) compared to those in the control group (no treatment) at all measurement points during treatment. Rat uterine weights in each treated group decreased significantly compared with those in the control group (P less than 0.05). There was no significant difference between ER-positive and ER-negative groups in tumor size, body weight or uterine weight. At increased doses of CGS 16949A in the experiment, further increases in testosterone levels and further decreases in estradiol levels were shown to occur. The results suggest the mechanisms of CGS 16949A action not to be influenced by the presence or absence of ER, but to be due to its potent aromatase inhibition of the conversion of androgens to estrogens.     

Interleukin-1 alpha modulates luteinizing hormone stimulated cyclic AMP and progesterone release from human granulosa cells in vitro.

This study examines the possible direct effect of interleukin-1 alpha (IL-1 alpha) upon human granulosa cells. The cells were isolated from follicles of stimulated cycles in women undergoing oocyte retrieval for in-vitro fertilization. Purified cell preparations were cultured for different time periods in the presence of IL-1 alpha and human luteinizing hormone (LH) or follicle stimulating hormone. IL-1 alpha stimulated basal as well as LH-induced progesterone accumulation. The response in terms of cyclic AMP was more complex, there was no effect of IL-1 alpha on basal cyclic AMP accumulation. However, at the highest concentration tested (50 IU/ml), IL-1 alpha enhanced cyclic AMP accumulation over that seen with LH alone. At a lower concentration, IL-1 alpha either had no effect or was slightly inhibitory to the LH-induced cyclic AMP accumulation, depending on the culture period. Our results, taken together with other findings, are compatible with the view that IL-1 alpha has a potential regulatory role in the granulosa-luteal cell transition in the human ovary.     

Preincubation of human granulosa cells with gonadotrophin prevents the cloprostenol-induced inhibition of progesterone production.

Human granulosa cells, from women undergoing ovum collection for in-vitro fertilization (IVF), will luteinize in vitro and provide a model for investigating the antigonadotrophic action of a prostaglandin F2 alpha (PGF2 alpha) analogue, cloprostenol, on granulosa-derived luteal cells. The granulosa cells were cultured in a defined medium and exposed to treatments during a preincubation period of 0 to 3 days and a final incubation with low density lipoprotein (LDL) from days 3 to 4. In the absence of human chorionic gonadotrophin (HCG), progesterone production was low, whereas exposure to HCG in the final incubation resulted in a 10-fold increase in progesterone concentrations. The inclusion of cloprostenol with HCG in the final incubation significantly (P less than 0.05) inhibited HCG-stimulated progesterone production. Exposure to HCG during the preincubation prevented the antigonadotrophic action of cloprostenol in the final incubation. The antigonadotrophic action of cloprostenol was retained when the granulosa cells were exposed to cloprostenol during the preincubation. Omission of LDL from the final incubation lowered the production of progesterone but the pattern of responses to HCG and cloprostenol were similar. Prevention of the antigonadotrophic action of cloprostenol after exposure to HCG may be a mechanism through which chorionic gonadotrophin can prevent regression of the corpus luteum in early pregnancy. Cloprostenol does not appear to inhibit LDL-stimulated steroidogenesis in human granulosa cells.     

Protooncogenes and growth factors associated with normal and abnormal liver growth

Hepatocyte replication during liver regeneration depends on extrinsic (circulating) and intrinsic (intrahepatic) factors. Two important growth factors produced in the regenerating liver are discussed, TGF, an autocrine, stimulatory growth factor, and TGF, a paracrine inhibitory factor. The balance between the activities of these factors is likely to play an important role in regulating hepatocyte proliferation. The experession of some protooncogenes occurs sequentially during the first few hours after partial hepatectomy and is a marker for the entry of hepatocytes into the cell cycle (proliferative competence). As hepatocytes become competent to proliferate, they respond to TGF and other growth factors and enter a proliferative phase. It is possible that TGF1 serves as a stop signal for liver regeneration but the mechanisms by which TGF inhibits hepatocyte DNA synthesis are still unknown.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.     

"Hyperfrontal" distribution of the cerebral grey matter flow in resting wakefulness; on the functional anatomy of the conscious state

Regional cerebral blood flow was measured with the intra-arterial 133 Xenon clearance technique using a multidetector device in 11 patients undergoing carotid angiography (with normal findings). During the flow studies the patients were awake and strict resting conditions were observed. The patients did not move or speak, and sensory stimulation were kept at a minimum. It was confirmed that the distribution of the grey matter blood flow showed a hyperfrontal pattern, the flow in frontal regions being significantly (20-40%) higher than in postcentral, occipital and temporal regions. There were no technical factors or morphological features of the telencephalon which could explain this difference. It was also shown that the distribution of the white matter flow and the relative weight of the grey matter corresponded in general to hemisphere morphology. Since in normal nervous tissue the blood flow is regulated by the neuronal activity, the following interpretation is given of the main finding. The hyperfrontal flow distribution of the grey matter (cortical) flow during resting wakefulness shows that there is a high activity in frontal "efferent" (motor-behavior) regions. At the same time there is a low activity in post-central and temporal "afferent" (sensory-gnostic) cortical areas. The high frontal activity suggests that in the resting conscious state--unaccompanied by movements, speech or behavioral reactions--the brain is active with an anticipatiory "simulation of behavior". The low postcentral flow, on the other hand, may possibly be related to a global inhibition of the sensory input. Several clinical as well as general biologic arguments are forwarded to support this interpretation. It is further pointed out that the hyperfrontal distribution of the resting activity in the cerebral cortex correlates to the resting EEG, in which lower frequencies (the alpha rhythm) predominate in postcentral and temporal regions where there is a low flow/activity, and high frequencies in frontal areas where the blood flow is high. This is in agreement with the finding that the blood flow and metabolism of the brain correlate to the EEG frequency content.     

AD治疗新药物——γ-分泌酶抑制剂

家族性阿尔采末病属常染色体显性遗传 ,其中大部分与编码早老素的基因发生突变所导致的γ 分泌酶功能异常有关 ,γ 分泌酶是一包括PS二聚体、Nicastrin、PEN 2等组分的多酶复合体。γ 分泌酶剪切APP、Notch、E cadherin、ErbB 4受体酪氨酸激酶等膜蛋白。目前已发现了许多类型的γ 分泌酶抑制剂 :基于二氟酮、二氟乙醇基团的γ 分泌酶抑制剂 ;脲多肽模拟化合物 ;基于羟乙基二肽电子等配体的化合物 ;具有α 螺旋结构的小肽 ;具有 4 氯 异香豆素基本母核的非肽抑制剂 ;含有丙氨酰基团的化合物。但这些抑制剂目前大多还只是作为一种工具药来研究γ 分泌酶的结构、功能以及作用机制。其中选择性抑制Aβ生成的γ 分泌酶抑制剂很有希望成为一种高效的阿尔采末病治疗药物     

头针对急性脑缺血再灌注大鼠脑内肿瘤坏死因子α表达影响的实验研究

目的 :观察头穴针刺对缺血再灌注大鼠脑内肿瘤坏死因子α(TNF αmRNA)表达的影响 ,探讨针刺治疗缺血性脑损伤的可能机制。方法 :采用大鼠局灶性脑缺血再灌注模型 ,应用原位杂交及HE染色方法观察脑缺血再灌注时TNF αmRNA的变化及缺血脑组织病理变化 ,以及针刺对其影响。结果 :假手术组大鼠TNF αmRNA在皮层、纹状体呈基础水平表达 ,脑缺血再灌注后12hrTNF αmRNA表达增强 (P <0 .0 5) ,针刺可明显抑制皮层、纹状体内TNF αmRNA的表达(P <0 .0 5) ,组织学中其神经组织变性、坏死及血管炎性反应也明显减轻。结论 :针刺对缺血性脑损伤的保护作用机制可能与针刺抑制脑内TNF αmRNA的表达有关     

192例恶性肿瘤患者应用重组人肿瘤坏死因子-α免疫功能与疗效的相关性分析

目的：观察重组人肿瘤坏死因子—α(rh—TNFα)静脉输注对恶性肿瘤患者细胞免疫功能的增强作用及影响因素，并分析其与rh—TNFα抗肿瘤作用的相关性。方法：选择具有明确病理诊断的复治或拒绝放、化疗的乳腺癌、恶性淋巴瘤、肾癌和恶性黑色素瘤患者，静脉输注rh—TNFα，100万U／m^2，每日1次，每周连续5日，连用4周为1个疗程。采用免疫荧光直标染色法染色，以流式细胞仪检测治疗前后患者外周血T细胞亚群、NK细胞变化，同时评价抗肿瘤治疗的疗效。治疗前后细胞免疫功能比较采用配对t检验，免疫功能变化与抗肿瘤客观疗效的相关性采用多因素Logistic回归分析。结果：rh—TNFα给药后可提高患者外周血NK细胞和T细胞亚群数量，但CD4／CD8比值变化不明显，NK细胞和T细胞亚群的变化与rh—TNFα的抗肿瘤客观疗效的相关性不显著。结论：rh—TNFα具有一定的改善肿瘤患者细胞免疫功能的作用，但这种免疫增强作用可能不是其抗肿瘤疗效的最主要机制。     

人肿瘤坏死因子-α基因转导绒癌耐药细胞系体外耐药逆转的研究

目的 将人肿瘤坏死因子-alpha(hTNF-α)基因导入已建立的绒癌耐药细胞系，观察hTNF-α基因转导后对绒癌细胞耐药性逆转的体外作用。方法 通过阳离子脂质体将hTNF-α基因转导绒癌耐药细胞系，用新霉素筛选含hTNF-α片段的单细胞克隆，用RT-PCR方法和细胞免疫组织化学方法，检测转导hTNF-α基因的耐药细胞中MDRl mRNA和MDRl蛋白(P-gp)表,达水平的改变。采用四甲基偶氮唑蓝比色法，检测转导hTNF-α基因的耐药细胞对足叶乙甙(VP-16)的耐药指数。结果 转导hTNF-α基因后，绒癌耐药细胞中检测出hTNF-α mRNA表达，转导hTNF-α基因在mRNA水平能一定程度的逆转绒癌耐药细胞的MDRl，而在P-gp蛋白水平几乎能完全逆转绒癌耐药细胞的MDRl。转导hTNF-α基因的细胞的耐药指数明显降低。结论 hTNF-α基因转导后，可通过调节MDRl的表达，来逆转绒癌耐药细胞系的耐药性。