环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Microsurgical anatomy of VII and VIII cranial nerves and related arteries in the cerebellopontine angle

Summary The relationships of VII and VIII cranial nerves and related arteries are reviewed in 26 preparations by microdissection techniques. These vessels may be grouped in large (AICA, PICA), medium (LA, SA, CSA, RPI) and small calibre (vasa nervorum, radicullar and medullar branches). The importance of these structures in acoustic neuroma surgery, vestibular neurectomy and cross-compression syndromes is discussed. Vascular loops and elongated arteries are normal structures present at birth.This work was supported by a grant from the AJ Roemmers Foundation     

Differential pattern of DNA-aneuploidy in human malignancies

The differential pattern of DNA-aneuploidy, detected by flow cytometry (FCM) regarding its frequency, grade and multiclonality, was investigated and correlated to tumor type, malignancy grade, tumor stage and prognosis in a multi-institutional study at the University of Münster. High resolution measurements using admixed normal blood reference cells were undertaken in 2413 cases of 13 different malignant diseases and in 776 benign lesions or samples. The incidence of DNA-aneuploidy was highest in melanomas, carcinomas, testicular tumors, sarcomas (75%-95%) and myelomas (65%). Acute leukemias showed an intermediate DNA-aneuploidy rate of 40% with special subgroups represented by common ALL (44%), p less than 0.05) and myelomonocytic/monocytic AML (47%, p less than 0.01). The lowest DNA-aneuploidy-rate was found in basal cell skin carcinomas (19%) and congenital melanocytic nevi (9%). No case of DNA-aneuploidy was observed in the 776 benign lesions or samples.--DNA-indices giving the grade of DNA-aneuploidy with 1.0 for normal diploid G1/0 cells were found distributed predominantly between 1.0 and 2.0 in the solid tumors, except testicular tumors, clustering around a triploid maximum at 1.5. DNA-indices of myelomas and acute leukemias generally ranged below 1.25 with lower DNA-aneuploidy grades in AML than in ALL (p less than 0.01).--In melanomas the aneuploidy rate was higher (86%) in metastases than in the primary tumors (54%, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Corticosteroids increase lipocortin I in alveolar epithelial cells

Lipocortin I mediates, in part, the anti-inflammatory effects of corticosteroids. To determine whether alveolar epithelial cells produce lipocortin I, we used a highly specific anti-lipocortin I antibody and found by the techniques of Western blotting and immunocytochemical analysis that lipocortin I is a normal constituent of type II alveolar epithelial cells and that it constitutes approximately 0.1% of cell lysate proteins. Two separate species of lipocortin I were identified, migrating with molecular weights of 37 and 32 kD. Dexamethasone caused a dose-dependent increase in lipocortin I in rat alveolar epithelial cells, and its effect was maximal at a dose of 10(-5) M. This effect was specific for corticosteroids since it was not seen with other steroids. These studies suggest that lipocortin I may mediate, in part, the immunosuppressive effects of corticosteroids in the lower respiratory tract.     

The immediate early genes of human cytomegalovirus require only proximal promoter elements to upregulate expression of interleukin-1 beta.

Human cytomegalovirus (HCMV) can infect monocytes and macrophages. The immediate early one (IE1) gene product of HCMV positively regulates its own expression, as well as the expression of the interleukin-1 beta (IL-1) gene. This study describes the IL-1 promoter proximal region required for upregulation of IL-1 gene expression by the HCMV IE1 or IE1 plus IE2 gene products. An IL-1 chloramphenicol acetyltransferase (CAT) construct containing the IL-1 genomic upstream sequence from position -1097 to +14 and four additional IL-1CAT plasmids containing progressive deletions of the -1097 to -131 sequence were used to evaluate the effect of the HCMV IE gene products on IL-1 gene expression. IL-1CAT plasmids were transfected into a monocytic cell line, THP-1, with plasmids containing either the IE promoter-regulatory region upstream of the bona fide IE1 (pIE1), IE2 (pIE2), or IE1+2 genes (pIE1+2) or a control plasmid containing the IE promoter-regulatory region alone (pLink760). In the presence of pIE1+2, there was an approximate 15-fold increase in CAT activity compared with the control, pLink760, in cells with CAT plasmids containing the -1097 to +14 IL-1 sequence. Plasmids with progressive deletions of this sequence, including the plasmid containing the shortest upstream segment (-131 to +14) also had an approximate 15-fold increase in CAT activity. The upregulation of IL-1 expression was mediated, primarily, by IE1 and not by IE2. This effect was promoter specific because an IL-1CAT plasmid with a complete deletion of the proximal promoter elements (-234 to +146) did not respond to the HCMV IE gene products.(ABSTRACT TRUNCATED AT 250 WORDS)     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Influence of inhaled corticosteroids on growth: a pediatric endocrinologist''s perspective

Given the increasing advocacy for the use of inhaled corticosteroids as a treatment of choice for persistent asthma, growing numbers of children are being exposed to the possible growth-suppressing effects of glucocorticoids. Recent evidence strongly suggests that, when consistently administered at moderate doses, inhaled corticosteroids (IC) are capable of slowing growth in children. Whether such growth suppression would persist and ultimately affect final adult height remains unknown. Therapeutic goals which aim for uninterrupted inflammatory disease control rather than periodic symptom control may increase the occurrence of growth failure in children treated with IC. In this article, current information about the mechanisms of growth suppression by glucocorticoids and the effects of IC on growth is reviewed, and recommendations for designing studies to investigate the effects of drugs on growth are presented.