c-erbB-2/p185-directed therapy in human lung adenocarcinoma

BACKGROUND: These experiments were conducted to determine whether p185 can be therapeutically targeted in adenocarcinoma of the lung using an anti-p185-gelonin conjugate. c-erbB-2/p185 is overexpressed in up to one third of non-small cell lung cancers. CALU-3 is a human lung adenocarcinoma cell line that overexpresses p185. muMoAb-4D5 is a murine anti-p185 monoclonal immunoglobulin G1. Gelonin is a potent type 1 ribosomal inhibitory protein. METHODS: 4D5 and gelonin were covalently modified and linked. Purification was confirmed by SDS-polyacrylamide gel electrophoresis. Dose-dependent cytotoxicity was quantified using 3H-thymidine uptake by CALU-3 cells after incubation with 4D5-gelonin conjugate or with control substances (4D5, gelonin, unconjugated 4D5 + gelonin, or control antibody MOPC-21). RESULTS: The 4D5-gelonin conjugate showed a 50% inhibitory concentration of 3.5 x 10(-10) mol/L, but 4D5 alone demonstrated no cytotoxic effect. Gelonin and the unconjugated 4D5-gelonin mixture had one tenth the cytotoxicity of the 4D5-gelonin conjugate (inhibitory concentration = 6.5 x 10(-9) mol/L and 8.5 x 10(-9) mol/L, respectively). The conjugate exhibited minimal toxicity against a p185-negative cell line (NIH3T3). CONCLUSIONS: Selective and efficient killing of human lung adenocarcinoma cells can be achieved in vitro using c-erbB-2/p185-directed therapy.     

Dermatology in southwestern Ethiopia: rationale for a community approach

The objective of our follow-up study was to evaluate the success of two different types of partially prefabricated post-and-core systems following crown placement. Two hundred and thirty-seven Permador posts and 49 Radix posts were evaluated clinically. Radiological follow-up was performed for 230 Permador posts and 47 Radix posts. The restorations had been in situ for an average of 3.9 years (Permador posts) and 2.3 years (Radix posts), respectively. Root canal fillings were evaluated as to their length, their homogeneity and their flushness with the walls of the root canal. The post-and-cores were evaluated for their orientation in the root canal and for the length of the inserted post relative to the length of the root. The position of the post was classified as centric in 78.0% of the restorations followed, and eccentric in 19.5%, while 2.5% showed a root perforation. The minimal requirement that the length of the post-and-core should at least be equal to the length of the clinical crown was met in 85% of the cases. Eighteen (6.3%) of the 286 teeth examined had to be extracted. There were significant correlations between insertion periods, horizontal bone loss, length of the root canal filling, and position of the post on one hand and tooth loss on the other.     

Linkage between operator binding and dimer to octamer self-assembly of bacteriophage lambda cI repressor

Cooperative binding of the bacteriophage lambda cI repressor dimer to specific sites of the phage operators OR and OL controls the developmental state of the phage. Cooperativity has long been thought to be mediated by self-assembly of repressor dimers to form tetramers which can bind simultaneously to adjacent operators. More recently, we demonstrated that when free repressor dimers self-associate in solution, tetramer is an intermediate in a concerted assembly reaction leading to octamer as the predominant higher order species [Senear, D. F., et al. (1993) Biochemistry 32, 6179-6189]. Even as a minority component in the assembly reaction, tetramer can account for pairwise cooperativity. In a similar manner, were it able to bind all three operators simultaneously, octamer could account for three-way cooperativity. In fact, based solely on repressor self-assembly, the naive prediction is that the repressor-OR interactions should be substantially more cooperative than they are. Evidently, there are unfavorable contributions to cooperativity from processes other than repressor self-assembly. Here, we focus on coupling between repressor self-association and operator binding as one possible unfavorable contribution to cooperativity. Sedimentation equilibrium analysis was used to compare the dimer-octamer association reactions of a repressor dimer-OR1 complex and free repressor dimer. Fluorescence anisotropy was used to investigate OR1 binding to free dimers and dimers assembled as higher order species. The results of these experiments indicate a significant and salt-dependent unfavorable contribution generated by such coupling. Since the oligonucleotides used in these experiments are the size of single operator sites, this coupling is mediated by the protein, not by the DNA. This mechanism does not account for an additional, salt-independent, unfavorable contribution which we presume is transmitted via the DNA. Thus, unfavorable contributions generated by structural transitions in both macromolecules serve to moderate the effect of self-association alone. We speculate that this is a general feature of cooperative protein-DNA interactions.     

疏松砂层微粒运移特征及对油井动态的影响

微粒运移伤害是疏松产层一种比较普遍又相当严重的地层伤害。本文着重讨论了水动力作用下孔隙微粒运移条件，结合室内实验分析了不同类型的驱动流体对运移产生的影响，最后应用实际生产数据对比分析了冀东油田馆陶组产层微粒运移伤害后油井的几种典型动态特征。     

Primary dedifferentiated leiomyosarcoma of the fallopian tube

Between 1960 and 1995 the University of Leipzig Women's Hospital encountered 44 cases of primary malignant tumors of the Fallopian tube, including four malignant Müller mixed tumors and one sarcoma. The sarcoma, a dedifferentiated leiomyosarcoma, was found incidentally in a 57-year-old woman. Treatment encompassed total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy and pelvic and para-aortic lymph node dissection, followed by telecobalt irradiation of the pelvis (Hd 52 Gy). One year after treatment, no evidence of disease recurrence, is found. Literature documents only 34 cases of a primary uterine tube sarcoma. Even with RO-resection, the early, high rate of local recurrence (most often within the first two years after treatment) and hematogenous metastasis to the lungs, liver and bones compose this tumor's clinical course. The prognosis is poor despite the use of radiotherapy and/or combination chemotherapy.     

Native-like beta-hairpin structure in an isolated fragment from ferredoxin: NMR and CD studies of solvent effects on the N-terminal 20 residues

The conformational properties of protein fragments have been widely studied as models of the earliest initiation events in protein folding. While native-like alpha-helices and beta-turns have been identified, less is known about the factors that underly beta-sheet formation, in particular beta-hairpins, where considerably greater long-range order is required. The N-terminal 20 residue sequence of native ferredoxin I (from the blue-green alga Aphanothece sacrum) forms a beta-hairpin in the native structure and has been studied in isolation by NMR and CD spectroscopy. Local native-like interactions alone are unable to stabilize significantly a folded conformation of the 20-residue fragment in purely aqueous solution. However, we show that the addition of low levels of organic co-solvents promotes formation of native-like beta-hairpin structure. The results suggest an intrinsic propensity of the peptide to form a native-like beta-hairpin structure, and that the organic co-solvent acts in lieu of the stabilizing influence of tertiary interactions (probably hydrophobic contacts) which occur in the folding of the complete ferredoxin sequence. The structure of the isolated hairpin, including the native-like register of interstrand hydrogen bonding interactions, appears to be determined entirely by the amino acid sequence. The solvent conditions employed have enabled this intrinsic property to be established.     

Increased risk for cancer in patients with the Peutz-Jeghers syndrome

BACKGROUND: Some reports describe an increased risk for cancer in patients with the Peutz-Jeghers syndrome. OBJECTIVE: To characterize occurrences of cancer in a large cohort of patients with the Peutz-Jeghers syndrome. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: 34 patients with the Peutz-Jeghers syndrome identified from Mayo Clinic records from 1945 to 1996. MEASUREMENTS: Cases of cancer documented by chart review and telephone follow-up. RESULTS: 26 cases of noncutaneous cancer developed in 18 of the 34 patients: 10 cases of gastrointestinal cancer and 16 cases of extraintestinal cancer. With the use of SEER (Surveillance, Epidemiology, and End Results) data for comparison, the relative risk for cancer was 18.5 (95% CI, 8.5 to 35.2) in women with the Peutz-Jeghers syndrome and 6.2 (CI, 2.5 to 12.8) in men with the syndrome (P = 0.001). In women, the relative risk for breast and gynecologic cancer was 20.3 (CI, 7.4 to 44.2). CONCLUSIONS: The Peutz-Jeghers syndrome is associated with an increased risk for cancer. The relative risk for breast and gynecologic cancers is particularly high.     

Canine filarial infections in north Taiwan

STUDY OBJECTIVES: Define the incidence of obstructive atelectasis in patients presenting with small cell lung cancer and their response to treatment. DESIGN: Retrospective review of clinical records and radiographic studies. SETTING: Single federal government institution-the National Cancer Institute-Naval Medical Oncology Branch. PATIENTS: One hundred seventy-two consecutive patients treated between 1983 and 1993. INTERVENTIONS: Patients presenting with obstructive atelectasis were identified. The incidence of dyspnea, cough, and sputum production before starting treatment and 1, 3, and 6 months later was determined. Fiberoptic bronchoscopy and chest radiographs performed before starting treatment were compared with those obtained later in the patients' clinical course. MEASUREMENTS AND RESULTS: Thirty-seven of 172 (22%) patients had obstructive atelectasis. Initial symptoms included cough in 25 (68%), dyspnea in 24 (65%), and productive cough in 10 (27%). The patients' symptoms of cough, dyspnea, and sputum production decreased to one third of the initial prevalence 1 month after the start of treatment. Fiberoptic bronchoscopy and chest radiographs performed 3 months after starting treatment demonstrated bronchial patency in 90%. CONCLUSIONS: Obstructive atelectasis occurs in approximately one fifth of patients presenting with small cell lung cancer. Chemotherapy and chemotherapy plus chest radiotherapy lead to symptomatic, bronchoscopic, and radiographic resolution in similar proportions of patients with obstructive atelectasis.