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     

Comparative nuclear magnetic resonance studies of diffusional water permeability of red blood cells from different species. VIII. Adult and fetal guinea pig (Cavia procellus)

The diffusional water permeability (P _d) of adult, pregnant female and fetal guinea-pig red blood cells (RBCs) was measured by a doping nuclear magnetic resonance (NMR) technique on control cells and following inhibition withp-chloromercuribenzene sulphonate (PCMBS). The values ofP _d were around 5.0 × 10^?3 cm/s at 15 °C, 5.3 × 10-3 cm/s at 20 °C, 6.6 × 10^?3 cm/s at 25 °C, 7.5 × 10^?3 cm/s at 30 °C and 8.6 × 10^?3 cm/s at 37 °C with no significant differences between adult, pregnant female and fetal RBCs. Systematic studies on the effects of PCMBS on water diffusion indicated that the maximal inhibition was reached in 10 min at 37 °C with 0.1 mm PCMBS. The values of maximal inhibition ranged from 70%–77% at 15–30 °C to 57%–63% at 37 °C in the case of adult and from 64%–67% at 15–30 °C to 51% at 37 °C in the case of fetal RBCs. The basal permeability to water was estimated at 1.1 × 10^?3 cm/s at 15 °C ,1.3 × 10^?3 cm/s at 20 °C, 1.6 × 10^?3 cm/s at 25 °C, 2.2 × 10^?3 cm/s at 30 °C and 3.2 × 10^?3 cm/s at 37 °C for adult and slightly higher values for fetal guinea pig RBCs as 1.6 × 10^?3 cm/s at 15 °C, 2.0 × 10^?3 cm/s at 20 °C, 2.4 × 10^?3 cm/s at 25 °C, 2.6 × 10^?3 cm/s at 30 °C and 4.2 × 10^?3 cm/s at 37 °C. The activation energy of water diffusion was around 22 kJ/ mol, with no significant differences between the adult pregnant female and fetal RBCs, and increased to about 40 kJ/mol in the case of adult and pregnant RBCs and 34 kJ/mol for fetal RBCs after incubation with PCMBS in conditions of maximal inhibition of water diffusion. The membrane polypeptide electrophoretic pattern of adult and fetal guinea-pig RBCs was compared with its human counterpart. The guinea-pig membrane contained higher amounts of spectrin (band 1 and 2), whereas the proteins in bands 4.1, 4.2 and 6 were present in lower amounts. Considerable differences in polypeptides migrating in the region of bands 7 and 8 and in front of them were apparent between the two sources of RBC membranes where some bands were present only in the guinea-pig RBC membranes. The adult guinea-pig membranes contained smaller amounts of proteins migrating in band 4.5 and lacked band 8.     

A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice

Collagen IV is a major structural component of basement membranes. In the glomerular basement membrane (GBM) of the kidney, the alpha3, alpha4, and alpha5(IV) collagen chains form a distinct network that is essential for the long-term stability of the glomerular filtration barrier, and is absent in most patients affected with Alport syndrome, a progressive inherited nephropathy associated with mutation in COL4A3, COL4A4, or COL4A5 genes. To investigate, in vivo, the regulation of the expression, assembly, and function of the alpha3alpha4alpha5(IV) protomer, we have generated a yeast artificial chromosome transgenic line of mice carrying the human COL4A3-COL4A4 locus. Transgenic mice expressed the human alpha3 and alpha4(IV) chains in a tissue-specific manner. In the kidney, when expressed onto a Col4a3(-/-) background, the human alpha3(IV) chain restored the expression of and co-assembled with the mouse alpha4 and alpha5(IV) chains specifically at sites where the human alpha3(IV) was expressed, demonstrating that the expression of all three chains is required for network assembly. The co-assembly of the human and mouse chains into a hybrid network in the GBM restores a functional GBM and rescues the Alport phenotype, providing further evidence that defective assembly of the alpha3-alpha4-alpha5(IV) protomer, caused by mutations in any of the three chains, is the pathogenic mechanism responsible for the disease. This line of mice, humanized for the alpha3(IV) collagen chain, will also provide a valuable model for studying the pathogenesis of Goodpasture syndrome, an autoimmune disease caused by antibodies against this chain.     

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.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.