Mutations in 16S rRNA that affect UGA (stop codon)-directed translation termination.

Site-directed mutagenesis was performed on a sequence motif within the 3' major domain of Escherichia coli 16S rRNA shown previously to be important for peptide chain termination. Analysis of stop codon suppression by the various mutants showed an exclusive response to UGA stop signals, which was correlated directly with the continuity of one or the other of two tandem complementary UCA sequences (bases 1199-1204). Since no other structural features of the mutated ribosomes were hampered and the translation initiation and elongation events functioned properly, we propose that a direct interaction occurs between the UGA stop codon on the mRNA and the 16S rRNA UCA motif as one of the initial events of UGA-dependent peptide chain termination. These results provide evidence that base pairing between rRNA and mRNA plays a direct role in termination, as it has already been shown to do for initiation and elongation.     

The significance ofheregulin in breast cancer tumor progression and drug resistance

Summary TheerbB-2 receptor plays an important role in the prognosis of breast cancer and is expressed at high levels in nearly 30% of tumors in breast cancer patients. While evidence accumulates to support the relationship betweenerbB-2 overexpression and poor overall survival in human breast cancer, understanding of the biological consequence(s) oferbB-2 overexpression remains elusive. The discovery ofheregulin has allowed us to identify a number of related but distinct biological endpoints which appear responsive to signal transduction through theerbB-2/4 receptor. These endpoints of growth, invasiveness, and differentiation have clear implications for the emergence, maintenance, and/or control of malignancy, and represent established endpoints in the assessment of malignant progression in human breast cancer. Preliminary studiesin vitro have shown thatheregulin induces a biphasic growth effect on cells witherbB-2 overexpression. Interestingly, we observed that expression ofheregulin correlates with a more aggressive/invasive, vimentin-positive phenotype in breast cancer cells lines. Therefore, we have postulated thatheregulin is involved in breast cancer tumor progression. We have shown thatheregulin inducesin vitro chemoinvasion and chemotaxis of breast cancer cells as well as growth in an anchorage dependent and independent manner. Interestingly, aheregulin neutralizing antibody inhibits chemotaxis and results in cell growth inhibition and blockade of the invasive phenotype. Strikingly, genetically engineered cells which constitutively expressheregulin demonstrate critical phenotypic changes that are associated with a more aggressive phenotype. Specifically, these cells are no longer dependent on estrogen for growth and are resistant to tamoxifenin vitro andin vivo, and moreover these cells metastasize to lymph nodes in athymic nude mice. These tumors appear to have lostbcl-2 expression as compared with the control tumors. In addition, presumably by activation/regulation of topoisomerase II, theheregulin-transfected cells become exquisitely sensitive to doxorubicin and VP-16. Clearly, mechanistic aspects of theerbB-2/4 andheregulin interaction need to be understood from a therapeutic standpoint which could provide additional insights into synergistic treatments for certain patients, or improve treatment regimens for a large number of women. The study ofheregulin and its co-expression witherbB-2/4 receptor and the assessment of its involvement in the progression from the in situ stage of breast tumors to the invasive one will additionally increase the relevance ofheregulin as a prognostic/diagnostic factor. We believe that our studies provide new insights into breast cancer diagnosis, prognosis, and treatment.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

Successful placement and re-expansion of a new balloon expandable stent to maintain patency of the ductus arteriosus in a newborn animal model

Objective: We performed this study in order to evaluate the usefulness of a new balloon expandable stent for maintaining ductal patency in a neonatal piglet model and to evaluate the ability to re-expand the stent weeks following initial implantation. Background: Maintaining patency of the ductus arteriosus without administration of Prostaglandin E has been reported previously using balloon dilation and stent implantation techniques. However, the experience is limited and the currently available stents are not modified for neonates. Methods: 14 newborn piglets all at age 12 days and median weight 3.6 Kg (range 2.7-4.3 Kg), underwent initial balloon dilation of the ductus arteriosus. Angiography after dilation demonstrated no significant left to right shunt. All piglets underwent successful stent (3.5 mm x 17 mm) placement in the ductus arteriosus. Results: Percutaneous ductal stent implantation via the arterial route was successful in all piglets with angiographic demonstration of a significant left to right shunt. Follow-up studies at weekly intervals with color flow Doppler were used to confirm patency of the stents. In 3 piglets the stent was not patent at initial follow-up and autopsy revealed sub-optimal stent placement. In two animals the stent was later re-expanded to 4 mm at 22 days, in one to 4 mm at 30 days and in one to 6 mm at 15 days, maintaining flow for an additional period of 15 to 34 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resection of clinically localized segments of painful retinaculum in the treatment of selected patients with anterior knee pain

We reviewed the long-term results of 25 patients who had localized soft tissue resections for refractory anterior retinacular knee pain. Patients completed visual analog scales to determine their activity and pain level changes, subjective assessment of their results, and whether they would have the surgery again under the same circumstances. Five of the 25 patients (20%) had had no knee surgery before the soft tissue excision, with the rest having had an average of two prior operations (range, 1 to 6). Subjectively, 22 patients (88%) noted moderate-to-substantial improvement after surgery; 3 patients (12%) declared no long-term benefit. All 25 patients stated that they would repeat the surgery under the same circumstances. Five patients (20%) noted a decrease in their results over time, but only two patients (8%) decreased their job level after surgery because of their knee pain. The average activity level dropped 60% after knee symptoms developed and increased 40% after surgery. Pain levels decreased 50% after surgery. The patients with the best overall results had lesions that were in the medial, inferomedial, or inferolateral retinaculum. The histologic results of the specimens included fibrosis, vascular proliferation, and small nerves with decreased myelin (neuromata). Our results show that specific soft tissue excision of painful tissue can often lead to successful clinical outcomes.     

腺点金丝桃挥发油化学成分分析

目的:研究腺点金丝桃挥发油成分及相对含量。方法:本文用水蒸气蒸馏,乙酸乙酯萃取法提取腺点金丝桃挥发油。采用GC-MS分析对其挥发油进行分离鉴定。结果:确定了41种成分,占挥发油总量的92.61,其中39种为首次报道。结论:萃取物中主要含:β-萜品烯反3.7-二甲基1.3.6-辛三烯、-顺3.7-二甲基1.3.6-辛三烯、δ-杜松萜烯、γ-杜松贴烯、长叶薄荷酮。