MMP-2及MMP-9表达在侵袭性垂体腺瘤中的生物学意义

目的本研究的目的是探讨基质金属蛋白酶-2(matrix metalloproteinase 2, MMP-2)及基质金属蛋白酶-9(matrix metalloproteinase 9, MMP-9)的表达与侵袭性垂体腺瘤相关性研究.以寻找垂体腺瘤侵袭性可能的发病机理.方法用免疫组化方法对54例垂体瘤患者的组织标本进行研究.并对其中16例患者采用逆转录-聚合酶链反应(RT-PCR)的方法对MMP-2及MMP-9 mRNA的表达进行分析.结果 54例垂体瘤患者中,有32例女性,22例男性.平均年龄为49.9岁(从18～76岁).其中,12例为侵袭性垂体腺瘤,42例为非侵袭性垂体腺瘤.免疫组化显示,侵袭性垂体腺瘤的MMP-2及MMP-9的表达明显高于非侵袭性垂体腺瘤(3.9±0.5; 2.3±0.2;P<0.01)和(4.1±0.4; 2.6±0.2; P<0.01).MMP-2及MMP-9的表达与MIB-1的表达无明显相关性(r=–0.05; P>0.05).侵袭性垂体腺瘤MMP-2及MMP-9 mRNA的表达,明显高于非侵袭性垂体腺瘤[(59.7±12.5)%; (33.3±5.4)%, P<0.05] 及[(68.2±15.3)%; (21.8±8.2)%; P<0.05] .结论 MMP-2及MMP-9的高表达与肿瘤的侵袭性密切相关.但与肿瘤的大小及分泌功能无明显关系.MMP-2及MMP-9可以作为肿瘤侵袭性一项有效的指标.肿瘤的侵袭性和增殖之间可能存在不同的生物学机制.     

Studies on the affinity and selectivity of denopamine (TA-064), a new cardiotonic agent, for beta-adrenergic receptors

Denopamine is a new orally active cardiotonic agent. The present experiment was carried out to characterize the binding affinity and selectivity of this drug for beta-adrenergic receptor subtypes. Binding studies were performed using 3H-dihydroalprenolol as the radioligand. Binding affinities of denopamine and some beta-agonists for rat heart membranes (KiH), which contain predominantly the beta 1-subtype, were in the order of isoproterenol (Iso, 14.1 nM) greater than prenalterol (158) greater than norepinephrine (Nor, 227) greater than or equal to epinephrine (Epi, 248) greater than denopamine (545) greater than or equal to dobutamine (645) greater than procaterol (1440) greater than terbutaline (6420). In rat lung membranes (predominantly beta 2-subtype), the order of potency (KiL) was Iso (20.6 nM) greater than procaterol (70.2) greater than Epi (136) greater than prenalterol (412) greater than dobutamine (735) greater than or equal to Nor (744) greater than denopamine (2205) greater than terbutaline (2500). The beta 1/beta 2-selectivity as judged from the KiL/KiH values was in the order of denopamine (4.1) greater than Nor (3.3) greater than prenalterol (2.6) greater than Iso (1.5) greater than dobutamine (1.1) greater than Epi (0.55) greater than terbutaline (0.39) greater than procaterol (0.05). Practolol, a beta 1-antagonist, showed a high beta 1-selectivity (KiL/KiH = 15.3). In the presence of guanine nucleotide (GTP), the denopamine radioligand competition curve showed a rightward shift, and its Hill coefficient increased like other agonists, although the degree of the shift was less than that observed with full agonists such as Iso. These results essentially correspond with the pharmacological and biochemical properties of denopamine and confirm the beta 1-selectivity and the agonist property of this compound.     

Pharmacokinetic and clinical evaluation of cefpirome in the pediatric field

Pharmacokinetic and clinical evaluations of cefpirome (CPR), a newly developed cephalosporin, were performed in the field of pediatrics. The results are summarized as follows. 1. Peak serum concentrations of CPR after a dose of 20 mg/kg via 30 minutes and that via 60 minutes intravenous drip infusion and a dose of 40 mg/kg via 60 minutes intravenous drip infusion were 80.8, 63.7 and 128.8 micrograms/ml, respectively, with half-lives being 1.41, 1.28 and 1.79 hours, respectively. Urinary excretion rates for CPR in the first 6 hours after administration ranged 66.7-77.1%. 2. The clinical efficacy rate in pediatric infections obtained at daily dose levels ranging 55.6-166.7 mg/kg was 95.7%. 3. The eradication rate for 22 strains identified in the study was 95.5%. 4. Side effects were found in 2 cases of diarrhea. The abnormal laboratory test results were observed in 5 cases with 7 test items (increased number of platelets; 2 cases, increased activity of GOT; 2 cases and increased activity of GPT; 1 case). According to these results, CPR was considered to be a useful antimicrobial agent in pediatric infections.     

Case report 685

We report an unusual case of an ossifying tumor arising in the deep soft tissue adjacent to the humerus of a 72-year-old woman. The tumor exhibited sarcoma-like features histologically, although its clinical course unexpectedly differed from that of a malignant tumor. We diagnosed this particular case as an ossifying fibromyxoid tumor of soft parts, which has been recently described by Enzinger et al.. This is another example of an ossifying soft-tissue tumor which simulates a malignant sarcoma.     

Activated oncogenes in a rat hepatocellular carcinoma induced by 2-amino-3-methylimidazo[4,5-f]quinoline

The presence of activated oncogenes in several rat hepatocellular carcinomas induced by 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) was examined by NIH 3T3 cell transfection assay and Southern blot analysis. In one tumor, IQ4, rat H-ras-1 and another oncogene that did not belong to the ras family were found to be activated.     

Transport characteristics of paraquat across rat intestinal brush-border membrane

The mechanism of absorption of paraquat, which is a type of quaternary ammonium compound (QAC), was studied using rat intestinal loops and brushborder membrane vesicles. Approximately 47% and 37% of radioactively labeled paraquat injected into jejunal and ileal loops disappeared, respectively, after 60 min. Since only a small amount of radioactivity was detected in the mucosal fraction, most of the paraquat that disappeared from the intestinal lumen was considered to have been carried away by the bloodstream, indicating that paraquat absorption was greater than expected. In spite of its low lipid solubility, the uptake of paraquat by brush-border membrane vesicles reflected smooth penetration into the intravesicular space rather than binding to the membrane. According to the increase in extravesicular paraquat concentration, paraquat uptake in the early stage was saturable. Moreover, early paraquat uptake was significantly inhibited by structurally-related QACs such as tetramethylammonium and choline, but not by an endogenous dicationic amine (putrescine). On the other hand, inside-negative membrane potential had no significant effect on the time course of paraquat uptake. From these results, it is suggested that paraquat is absorbed through a specialized mechanism associated with the carrier-mediated transport system for choline on the brush-border membrane.