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61.
As part of our ongoing studies to characterize molecular alterations in a well-defined series of surgically resected esophageal cancers, we examined the expression of 2 ras-regulated genes, whose products (osteopontin and cathepsin L) previously were shown to be associated with tumor invasion and metastasis. RNA was extracted from primary esophageal tumors (adenocarcinomas, 19; squamous-cell carcinomas, 6) and matched histologically normal esophageal mucosa from the distant resection margin. Northern analysis was used to quantitate RNA, relative to an 18S rRNA control, and immunohistochemistry to assess the tissue distribution of osteopontin. In addition, H-, K- and N-ras mutations were studied in the same tissues using PCR and hybridization with allele (mutant)-specific oligonucleotide probes. We demonstrated a K-ras mutation (codon 12, GTT) in one esophageal adenocarcinoma. The ras-regulated gene osteopontin was over-expressed in 100% of squamous-cell carcinomas and in 58% of adenocarcinomas relative to matched normal esophageal mucosa. Patterns of immunoreactivity for osteopontin protein also varied between squamous-cell carcinomas (tumor cell staining) and adenocarcinomas (predominantly tumor-infiltrating macrophages). Expression of cathepsin L also varied with esophageal tumor histology, with over-expression in 58% of primary esophageal adenocarcinomas and 33% of squamous-cell cancers.  相似文献   
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CI-980 (NSC 613862) is one of a novel class of 1,2-dihydropyrido[3, 4-b]pyrazines that inhibits tubulin polymerization, presumably by binding to the colchicine binding site of tubulin. In a Phase I and pharmacological study, 16 patients with advanced solid neoplasms were treated with CI-980 on a continuous 72-h infusion schedule at doses ranging from 3.0-5.4 mg/m2/day every 3 weeks. High rates of central nervous system (CNS) toxicity and neutropenia occurred in both minimally and heavily pretreated patients who were treated with CI-980 doses above 3.75 mg/m2/day, which is the maximum tolerated dose and the recommended dose for additional evaluations. CNS effects, characterized by neurocortical, mood, and cerebellar manifestations, were generally observed toward the end of the infusion and immediately posttreatment and usually resolved within 48 h after the completion of treatment. Toxicity was mild to modest at the 3.75 mg/m2/day dose level. Neither clinical nor pharmacological risk factors that may predispose patients to the development of CNS effects were evident. Although no objective antineoplastic activity was observed in this Phase I study, CI-980 steady-state plasma concentrations achieved at the recommended dose of 3.75 mg/m2/day (mean +/- SE, 5.74 +/- 0.54 nM) approached and exceeded concentrations that have been associated with significant activity in preclinical studies, indicating that additional disease-directed evaluations of CI-980 may be warranted.  相似文献   
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Compositions of Ni0.32Zn0.68-2xLixFe2+xO4 with x=0.0, 0.025, 0.050, 0.075, 0.100, 0.125, 0.150, 0.175, 0.200 were prepared by oxalate precursors. The Ms–T curves resemble type R. The magnetic moment (nB) values were found to increase with increase of Li1+ content up to x=0.175, and thereafter it decreased. The former explained on the basis of the exchange interactions, whereas the decrease of nB is related to the migration of Ni to tetrahedral (A) sites. There is a decrease in Yafet–Kittle (Y–K) angles at octahedral (B) sites, suggesting that lithium does not favor Hc canting. Actually, Li1+ tends to reduce canting, resulting in the increase of nB coercive force (Hc) and remanance ratio (R) variations have been related to increase of anisotropy constant (Kl) with increasing Li1+ content. The values of R are comparable with the theoretical value, 0.87, which is probably due to the very high density of the samples. Thermal variations of Hc and R reveal that neither parameter changes rapidly with increasing temperature, indicating that the material contains multi-domain (MD) grains in predominance. These results are also supported by a.c. susceptibility studies. The values of wall susceptibility are higher than those of rotational susceptibility, suggesting that the susceptibility is contributed mainly by the domain wall motion.  相似文献   
64.
Until fairly recently, investigations into the control of cell production (proliferation) have been the mainstay of studies into the maintenance of mucosal homeostasis and general integrity. However, in addition to proliferation, it is now increasingly evident that programmed cell death, specifically that form of programmed cell death known as apoptosis, is an equally, if not more important, mechanism of regulating mucosal cell number. This review will concentrate on the significance of damage (radiation) induced and spontaneous apoptosis in the maintenance of intestinal epithelial stem cell number and integrity, and its probable link to the level of cancer incidence in the small intestine and colon.  相似文献   
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AIM OF STUDY: Intrathecal sufentanil has recently been used in labour as part of a combined spinal epidural technique. This study was conducted to compare its use in combination with bupivacaine for caesarean section with fentanyl added to bupivacaine and bupivacaine alone. METHODS: Sixty ASA I and II patients for non-emergency caesarean section under spinal anaesthesia were divided into three groups to receive 15 micrograms fentanyl added to 7.5 mg bupivacaine, 10 micrograms sufentanil added to 7.5 mg bupivacaine and 7.5 mg bupivacaine. Onset time of sensory blockade, side effects, surgical conditions, neonatal outcome and quality of the anaesthetic was assessed. On the first postoperative day, duration of effective analgesia, side effects and patient satisfaction were noted. RESULTS: The duration of effective analgesia of bupivacaine alone was prolonged with the addition of sufentanil and fentanyl by 358% and 256% respectively. No patient in the sufentanil and fentanyl groups required additional intra-operative analgesics compared with 17.6% of patients in the bupivacaine alone group. There was an increase in incidence of desaturation in the sufentanil group (45%) and fentanyl group (5.6%) compared with the bupivacaine only group (0%). The incidence of pruritus was 35% with sufentanil, 27.8% with fentanyl against 0% with bupivacaine alone. CONCLUSION: The addition of 10 micrograms of sufentanil and 15 micrograms of fentanyl to 7.5 mg of bupivacaine prolonged the duration of effective analgesia and improved intra-operative analgesia. However, the incidence of pruritus and episodes of desaturation were increased more with 10 micrograms sufentanil than with 15 micrograms fentanyl.  相似文献   
67.
Recombinant adeno-associated virus vectors (AAV) were prepared in high titer (10(12) to 10(13) particles/mL) for the expression of human factor IX after in vivo transduction of murine hepatocytes. Injection of AAV-CMV-F.IX (expression from the human cytomegalovirus IE enhancer/promoter) into the portal vein of adult mice resulted in no detectable human factor IX in plasma, but in mice injected intravenously as newborns with the same vector, expression was initially 55 to 110 ng/mL. The expression in the liver was mostly transient, and plasma levels decreased to undetectable levels within 5 weeks. However, long-term expression of human F.IX was detected by immunofluorescence staining in 0.25% of hepatocytes 8 to 10 months postinjection. The loss of expression was likely caused by suppression of the CMV promoter, because polymerase chain reaction data showed no substantial loss of vector DNA in mouse liver. A second vector in which F.IX expression was controlled by the human EF1alpha promoter was constructed and injected into the portal vein of adult C57BL/6 mice at a dose of 6.3 x 10(10) particles. This resulted in therapeutic plasma levels (200 to 320 ng/mL) for a period of at least 6 months, whereas no human F.IX was detected in plasma of mice injected with AAV-CMV-F.IX. Doses of AAV-EF1alpha-F. IX of 2.7 x 10(11) particles resulted in plasma levels of 700 to 3, 200 ng/mL. Liver-derived expression of human F.IX from the AAV-EF1alpha-F.IX vector was confirmed by immunofluorescence staining. We conclude that recombinant AAV can efficiently transduce hepatocytes and direct stable expression of an F.IX transgene in mouse liver, but sustained expression is critically dependent on the choice of promoter.  相似文献   
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Cells of nasal placode of chick embryos were studied with thymidine H3 and autoradiography. Our results shown, that the nuclei in the nasal placode synthesize DNA in the outer zone, then migrate toward the inner zone to undergo division and subsequently return to the outer zone.  相似文献   
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