Inoperable adenocarcinoma of endometrium: radiation therapy

Between 1960 and 1979, 41 patients with adenocarcinoma of the endometrium who were poor surgical risks were treated with radiation therapy at the University of Iowa. Local tumor control was achieved in 78% of the patients, 5% manifested complications, and 46% survived 5 years ("uncorrected" 5-year survival rate). Intercurrent disease was the major cause of death (54%), and intrauterine recurrence (22%) was the most frequent recurrence. Intraperitoneal spread (12%) occurred as commonly as hematogenous metastases (12%). Three of nine local failures occurred after 5 years. Local control rates correlated well with clinical stage, and the survival rates correlated well with the stage and grade of the tumor. Local tumor control was achieved in 95% of patients who received greater than 7,000 mg-h intracavitary radium, compared with 63% of patients treated with less than 7,000 mg-h.     

腹腔镜胆囊切除术后腹壁肌间囊肿1例

1　病例报告　女 ,38岁 . 1 998- 1 0 - 2 0因右腰部包块逐渐增大 1 a入院 . 1 a前患者洗澡时发现右腰部核桃大小包块 ,逐渐增大且隐痛 ,不伴发热、盗汗及消瘦 ,饮食及大、小便正常 .患者于 3a前曾因胆囊结石在某院行腹腔镜胆囊切除术 ,术中经腹壁戳创口取出胆囊时 ,胆囊破裂 ,术后并发腹壁戳创口感染 ,并从戳创口夹出数枚米粒大小结石 ,经换药治愈 .查体 :T 36℃ ,肥胖 .于右腰区见 1 5 cm× 1 0 cm× 5 cm包块 ,皮色如常 ,皮温不高 ,包块质软 ,有囊性感 ,边界欠清 ,基底部固定 ,活动度差 ,无明显压痛 .B超 :右侧腹壁囊性包块 ,壁不规则增…     

IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome

The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al. reported homozygosity for a single mutation in KVLQT1 , a gene which has previously been shown to be mutated in families with dominantly inherited isolated long QT syndrome [Neyroud et al . (1997) Nature Genet ., 15, 186-189]. We have analysed a group of families with JLNS and shown that the majority are consistent with mutation at this locus: five families of differing ethnic backgrounds were homozygous by descent for markers close to the KVLQT1 gene and a further three families from the same geographical region were shown to be homozygous for a common haplotype and to have the same homozygous mutation of the KVLQT1 gene. However, analysis of a single small consanguineous family excluded linkage to the KVLQT1 gene, establishing genetic heterogeneity in JLNS. The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the gene IsK . This codes for a transmembrane protein known to associate with KVLQT1 to form the slow component of the delayed rectifier potassium channel. Sequencing of the affected boys showed a homozygous mutation, demonstrating that mutation in the IsK gene may be a rare cause of JLNS and that an indistinguishable phenotype can arise from mutations in either of the two interacting molecules.      

Molecular basis of the brindled mouse mutant (Mo(br)): a murine model of Menkes disease

The brindled mouse mutant (Mo(br)) is the closest animal model of the human genetic copper deficiency, Menkes disease, which is presumed to be due to a mutation at the X-linked mottled locus (Mo). The mutant mice are hypopigmented and die at around 15 days after birth, but can be saved by treatment with copper before the 10th postnatal day. Menkes disease has been shown to be due to mutations of the gene ATP7A which encodes P-type ATPase (referred to here as MNK). MNK is likely to function in copper efflux from cells, but the full range of its biological activity is not fully understood. The nature of the mutation in the brindled mouse is of importance in our understanding of the role of MNK and for devising treatment strategies for Menkes disease. Here we show that the brindled mouse has a deletion of two amino acids in a highly conserved, but functionally uncharacterized, region of Mnk. Comparison with the Ca ATPases suggests this region may be involved in conformational changes associated with the E1/E2 transition fundamental to the action of P-type ATPases. We also describe the first Western blot data for Mnk in tissues, and these show normal levels of Mnk in mutant and brindled kidneys but none in liver. In the kidney, immunohistochemistry demonstrated Mnk in the proximal and distal tubules, the distribution is identical in mutant and normal. This distribution is consistent with Mnk being involved in copper resorption from the urine.      

Construction of a mouse model of Charcot-Marie-Tooth disease type 1A by pronuclear injection of human YAC DNA

Construction of animal models of human inherited diseases is particularly important for testing gene therapy approaches. Towards this end, we constructed a mouse model for Charcot-Marie-Tooth disease type 1A by pronuclear injection of a YAC containing the human PMP22 gene. In one transgenic line, the YAC DNA is integrated in about eight copies and the PMP22 gene is strongly expressed to give a peripheral neuropathy closely resembling the human pathology. The disorder is dominant, causes progressive weakness of the hind legs, and there is severe demyelination in the peripheral nervous system including the presence of onion bulb formations. This approach will be valuable for pathologies produced by over-expression of a gene including trisomy and amplification in cancer. Such models will be particularly useful for testing gene therapy approaches if the transgene is human.      

Functional analysis and intracellular localization of the human menkes protein (MNK) stably expressed from a cDNA construct in Chinese hamster ovary cells (CHO-K1)

The Menkes protein (MNK or ATP7A) is an important component of the mammalian copper transport pathway and is defective in Menkes disease, a fatal X-linked disorder of copper transport. To study the structure and function of this protein and to elucidate its role in cellular copper homeostasis, a cDNA construct encoding the full-length MNK protein was cloned into a mammalian expression vector under the control of the CMV promoter. Transfection of this plasmid construct into CHO-K1 cells yielded clones that expressed MNK at varying levels. Detailed characterization of four clones showed that an increase in MNK protein expression led to a corresponding increase in the level of copper resistance of the cells. Subcellular localization studies showed that in the parental CHO-K1 and the transfected cell lines, MNK was located in a post-Golgi compartment which, based on immunogold electron microscopic analyses, most likely represented the trans -Golgi network (TGN). When the extracellular copper concentration was increased, MNK in the clones as well as in CHO-K1 cells was redistributed to the cytoplasm and plasma membrane, but returned to the TGN under basal, low copper conditions. This report presents the first ultrastructural evidence for the association of MNK with vesicles within the cell and with the TGN and plasma membrane. It also demonstrates the stable expression of a functional MNK protein from a cDNA construct in mammalian cells, as well as the copper-induced redistribution of MNK in a cell line (CHO-K1) that was not selected for copper resistance or overexpression of MNK.      

In-vivo administration of progesterone inhibits the secretion of endometrial leukaemia inhibitory factor in vitro

Human interleukin for DA cells, also called leukaemia inhibitory factor (LIF), is of cardinal importance for successful murine embryo implantation. Recent studies suggest it may also play an important role in human embryo implantation. Our objective was to study the hormonal regulation of the production/secretion of LIF by the human endometrium. Endometrial LIF secretion in specimens obtained from women without ovarian function (n+/-14) at day 10 (4 mg of oestradiol regimen) or day 20 (oestradiol plus 300 mg of progesterone) of a simulated menstrual cycle was examined. LIF was detected in all cultured explants obtained both in the proliferative and secretory phase of the stimulated cycles. The levels of cytokine production by day 10 endometrial culture explants were 5-fold higher than by day 20 endometrial samples (mean+/- SEM, 24.3+/-8.6 versus 4.5+/-2.1 pg/mg, P < 0.01). This suggests that progesterone significantly down-regulates the endometrial LIF secretion. The effect of progesterone on LIF secretion by the endometrium in vitro was also examined. Explants of endometrium obtained from the same patients on day 10 of cycle were treated with 0.5 ng/ml of progesterone in vitro. This progesterone treatment significantly reduced LIF secretion by endometrial explants in vitro (mean+/-SEM, 20.3+/-4.8 versus 10.7+/-2.3 pg/mg, P < 0.05). These results suggest that LIF endometrial production is regulated by progesterone both in-vivo and in-vitro. The possible mechanisms of LIF regulation are discussed briefly.