Juvenile Xanthogranuloma on the Palm

Abstract: Juvenile xanthogranuloma is a xanthomatous and granulomatous condition that frequently arises before 1 year of age and mainly occurs on the head and trunk. We report a rare solitary juvenile xanthogranuloma on the right palm of a 10-year-old girl, present for one year. This solitary involvement of the palm has been reported only twice before.     

Antitumor activity of five new platinum complexes having a glycolate leaving ligand.

In an attempt to develop a new anticancer platinum complex with greater or equivalent antitumor activity but reduced side effects compared with cisplatin (CDDP), a series of new platinum complexes having a glycolate leaving ligand was synthesized. Among them, five complexes were selected for further development on the basis of adequate water solubility, low nephrotoxicity and high antitumor activity in a murine system. The chemosensitivity of these five complexes was examined in MTT assay against two human pulmonary adenocarcinoma cell lines, PC-9 and PC-14, and two human stomach adenocarcinoma cell lines, MKN-45 and KATO III. Their IC50 and relative antitumor activity (RAA) values were compared with those of CDDP and 254-S, a second-generation platinum complex with a glycolate leaving ligand under phase III clinical trial. The lowest mean IC50 value was observed in CDDP, followed by SKI 2034R and SKI 2033R. In this study, the antitumor activity was evaluated in terms of RAA values and SKI 2034R showed the highest RAA value. The order of RAA values was SKI 2034R > CDDP > SKI 2032R > SKI 2033R > SKI 2030R > SKI 2029R > 254-S. Based on the RAA order, we have recommended SKI 2034R as the most promising candidate for further development of a clinically useful platinum complex.     

Microvascular corrosion casting of normal tissue, transitional mucosa and adenocarcinoma in the human colon.

The microcirculatory architecture of normal tissue, transitional mucosa and adenocarcinoma of the human colon was investigated with microvascular corrosion casting (MVCC) combined with scanning electron microscopy (SEM). The study showed that the capillaries within the normal mucosa were arranged in a regular hexagonal pattern around the mucosal glands and that the microvessels of transitional mucosa mostly had lost the typical hexagonal pattern and become slightly wider in diameter. The microvessels in the tumor periphery were increased in number and disorganized, and presented large variation in morphology with claw-like formations, widened sinuses, diverticula and appendixoid patterns. Microvessels were lacking in the central areas of tumors. These morphological alterations may serve as additional indicators of tumor development.     

Structure-activity relationships of (+)-CC-1065 analogues in the inhibition of helicase-catalyzed unwinding of duplex DNA.

(+)-CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis. Previous studies have shown that the potent cytotoxic and antitumor activities of (+)-CC-1065 are due to the ability of this compound to covalently modify DNA. (+)-CC-1065 reacts with duplex DNA to form a (N3-adenine)-DNA adduct which lies in the minor groove of DNA overlapping with a five base-pair region. As a consequence of covalent modification with (+)-CC-1065, the helix bends into the minor groove and also undergoes winding and stiffening. In the studies described here, we have constructed templates for helicase-catalyzed unwinding of DNA that contain site-directed (+)-CC-1065 and analogue DNA adducts. Using these templates we have shown that (+)-CC-1065 and select synthetic analogues, which have different levels of cytotoxicity, all produce a significant inhibition of unwinding of a 3'-tailed oligomer duplex by helicase II when the displaced strand is covalently modified. However, the extent of helicase II inhibition is much more significant for (+)-CC-1065 and an analogue which also produced DNA winding when the winding effects are transmitted in the opposite direction to the helicase unwinding activity. This observed pattern of inhibition of helicase-catalyzed unwinding of drug-modified templates was the same for a 3'-T-tail, for different duplex region sequences, and with the Escherichia coli rep protein. Unexpectedly, the gel mobility of the displaced drug-modified single strand was dependent on the species of drug attached to the DNA. Last, strand displacement by helicase II coupled to primer extension by E. coli DNA polymerase I showed the same pattern of inhibition when the lagging strand was covalently modified. In addition, the presence of helicase II on single-stranded regions of templates caused the premature termination of primer extension by DNA polymerase. These results are discussed from the perspective that (+)-CC-1065 and its analogues have different effects on DNA structure, and these resulting structural changes in DNA molecules are related to the different in vivo biological consequences caused by these drug molecules.     

Cyclosporine overcomes cold preservation/reperfusion injury of liver graft: Chemokine release and liver ultrastructure

There is a growing body of evidence that the cytokine, tumor necrosis factor-α (TNF-ga), plays an important role in the development of hepatic ischemia/reperfusion injury. We found that the immunosuppressants, cyclosporine-A (CsA), azathioprine, and FK506, have protective effects on such injury. The purpose of the present study was to elucidate mechanisms involved in these beneficial effects of the immunosuppressant, CsA, on liver injury following cold preservation and transplantation, with special reference to the suppression of TNF-α release. Rat livers were stored in Euro-Collins solution (EC) at 4°C for 6h and orthotopically transplanted. The animals allotted to two groups: group A (untreated controls) and group B (CsA pretreatment of recipients). CsA (10 mg/kg, p.o.) was given for 3 consecutive days preoperatively. CsA pretreatment of the recipients significantly improved the 2-week survival rate (0/6 for group A, 3/6 for group B;P<0.05) and this was associated with a significant decrease in serum TNF-α levels 2h posttransplantation (group A, 69.8±15.7 pg/ml; group B, 22.8±6.8; mean±SEM;n=12 each;P<0.05) and amelioration of sinusoidal endothelial injury, assessed by electron microscopy. Plasma endotoxin levels following reperfusion of the grafts were not altered by the CsA therapy. Morphologically, CsA pretreatment of the recipients did not alter activation of Kupffer cells. CsA pretreatment of the recipient aids in preventing cold preservation/reperfusion injury of the liver graft, possibly by modulating effects of TNF-α.     

白细胞介素—2新的功能位点及其中枢镇痛作用

白细胞介素－２（ＩＬ－２）不仅是重要的免疫调节因子，而且还具有重要的中枢调节作用。本实验以钾离子透入引起大鼠甩尾反应为指标，发现侧脑室注射ＩＬ—２能显著提高动物痛阈，并能被纳洛酮所阻断，表示ＩＬ－２的中枢镇痛作用可能与阿片受体有关。利用基因定位突变技术获得的无免疫活性ＩＬ－２实查体仍具有中枢镇痛作用，表明ＩＬ—２分子上发挥镇痛和免疫调节作用的功能位点是相互独立的。纳洛酮能够阻断ＩＬ—２的中枢镇痛作用，而不能影响ＩＬ—２增殖ＣＴＬＬ－２细胞的作用，提示ＩＬ－２发挥镇痛和免疫调节作用可能通过不同的受体途径。ＩＬ－２分子中第４５位Ｔｙｒ残基突变为Ｖａｌ后，虽仍保留了免疫活性，但丧失了镇痛功能，表示４５位Ｔｙｒ残基是ＩＬ—２发挥中枢镇痛功能的关键残基之一。我们推测ＩＬ—２的镇痛功能位点可能在ＩＬ—２分子中第４５位Ｔｙｒ残基附近区域。     

A comparative study of pepsinogen (PG) and lactic acid dehydrogenase (LDH) activities and isoenzyme patterns in tissues from human primary gastric cancer, gastric cancer xenografts in nude mice and gastric cancer cell lines]

Tissue and cell homogenates were prepared for PG and LDH study from 20 samples of histologically proven gastric cancer (GC), 6 samples of gastric cancer xenografts (THPGC-1) of different passages (GCXG) and cultured cells of 3 different gastric cancer cell lines (GCCL). Normal gastric mucosa (NGM) was also obtained from the resected stomach far distant from the primary tumor and histologically tumor free. The results indicated that the expression of PG isoenzymes was low or absent and the PG activities were significantly decreased in GC, GCXG and GCCL as compared to NGM. The activity of LDH was also significantly increased in GC, GCXG and GCCL. In addition, there was a change in isoenzyme pattern in GC and GCXG in which isoenzyme type M was observed whereas isoenzyme type H was preponderent in NGM. The results show that the human gastric cancer xenograft, THPGC-1, has biological properties very similar to those of the primary tumor suggesting that THPGC-1 is a reliable model for the study of the molecular biology of human gastric cancer.     

诺迪康对心脏活动的药理学作用

目的 :探讨诺迪康对心脏活动的药理学作用。方法 :运用 ms2 0 0 0多媒体生物信号处理系统 ,经 Straub法制备离体蛙心灌流标本并检测心脏活动 ,利用血流动力学方法检测家兔的心室活动等相关指标。结果 :2 0 9mg/L 诺迪康组的心肌收缩力增强 4 0 .38% (n =2 1,P <0 .0 0 1) ,4 18mg/L 诺迪康组的心肌收缩力增强 76 .4 4 % (n =17,P <0 .0 5 ) ,6 2 7mg/L 诺迪康组的心肌收缩力增强 10 4 .95 % (n =2 5 ,P <0 .0 1) ,对照组的心肌收缩力无明显变化 (n =2 5 ,P >0 .5 ) ;三个实验组及对照组对离体蛙心率均无作用 ,P >0 .0 5 ;家兔血流动力学方面 ,诺迪康组的 dp/dtmax增加了 2 1.0 8% (n =10 ,P <0 .0 5 ) ,其他各指标在对照组及诺迪康组均未见显著变化。结论 :诺迪康能增强心肌收缩力且有明显的剂量效应关系 ,可加速心肌的收缩速度但对心肌舒张无明显影响     

Embryology of the human fetal hippocampus: MR imaging,anatomy, and histology.

PURPOSETo identify changes in the embryology of the hippocampus responsible for its adult anatomy.METHODSTen human fetal specimens ranging from 13 to 24 weeks'' gestational age were examined with MR imaging. Dissections and histologic sections of 10 different specimens of similar ages were compared with MR imaging findings.RESULTSAt 13 to 14 weeks'' gestation, the unfolded hippocampus, on the medial surface of the temporal lobe, surrounds a widely open hippocampal sulcus (hippocampal fissure). At 15 to 16 weeks, the dentate gyrus and cornu ammonis have started to infold. The hippocampal sulcus remains open. The parahippocampal gyrus is larger and more medially positioned. The CA1, CA2, and CA3 fields of the cornu ammonis are arranged linearly. The dentate gyrus has a narrow U shape. By 18 to 20 weeks, the hippocampus begins to resemble the adult hippocampus. The dentate gyrus and cornu ammonis have folded into the temporal lobe. The hippocampus and subiculum approximate each other across a narrow hippocampal sulcus. The CA1-3 fields form an arc and the CA4 field has increased in size within the widened arch of the dentate gyrus.CONCLUSIONMR imaging of fetuses provides a developmental basis for understanding hippocampal anatomy.