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Volume 0 ， Issue 4 ， 2001
- Abstract：Objective. To examine the effect of isobutyramide synthesized in our laboratory on human and murine globin gene expression and to test cell toxicity ofthe drug.Methods. MEL cells were transfected with the recombinant construct μLCRAγψβδβand the stable transformants were cultured in the medium with different concentrations of isobutyramide. The experimental mice and rabbit were injected with different doses of isobutyramide. The globin mRNAs were analyzed by RNase protection assay. The hematological toxicity and electrolyte toxicity ofthe drug were tested.Results. An inducible and dose dependent expression of the human γ , β and mouse α globin gene was observed in the transfected MEL cells. The induction of the human γ globin gene is significant stronger than that of the β globin gene. With 2.5～5 mmol/L isobutyramide, the induction of the human γ globin gene is even more effective than that of mouse α globin gene. After a 15 day injection under the doses of 500～900mg·kg-1·d-1, the level of the mouse embryonic εy globin mRNA could be significantly induced up to 3～4 fold of that of uninjected controls. The changes of hemoglobin（Hb）, RBC, hematocrit（HCT）, WBC, derived from mice injected with different doses of isobutyramide at the interval of 24 hours for 2～4 weeks, were generally within the normal range. In rabbits injected with isobutyramide in the same regiment for 2 weeks, the concentration of blood K+, Na+, Cl-and CO2 were all within normal range and serum ionic osmotic pressure remained stable as well. Conclusion. Our results suggested that isobutyramide is a weak inducer ofcell differentiation, but it can selectively activate transcription of human γ globin gene at a certain degree, and it can act on early stages of erythroid progenitor differentiation in adult mice and activate transcription of embryonic εy-globin gene and have no hematological toxicity. Our results have further proved the potential value of isobutyramide in treatment of β-thalassemia and sickle cell disease.Keywords：isobutyramide;human fetal γ globin gene;murine embryonic εy globin gene;β thalassemia4|15|0Updated：2024-04-10
- Abstract：A rabbit anti serum to tree shrew apolipoprotein C I （apo C I） was used to screen an expression cDNA library constructed by us from tree shrew （TS）liver tissue. Two apo C I cDNA clones were obtained. The longer one consistsof 380 nucleotides, including 21 bp and 95 bp at the 5’ and 3’ end of the non translated regions respectively, and a 264 bp fragment in an open reading frame encoding 88 amino acids prepropeptide which contains 26 amino acids of signal peptide and a mature protein （62 amino acids）. Comparing the amino acid sequence deduced from this cDNA with those of the published mammalian apo C Is reveals that it shared some structural similarity with rat, mouse and dog apo C I, but it had 5 more amino acids than that of human and baboon. The expression of apo C I mRNA in 8 different tissues were also assayed with Northern blot. The results demonstrated that liver had the highest expression, intestine had much less expression and no expression in other tissues, which is much different from human and other species. This study has laid down a good foundation for further studying on the function and the stucture of tree shrew apo C I gene.Keywords：tree shrew;apolipoprotein C I;expression4|13|0Updated：2024-04-10
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- Abstract：Objective. To clone complete EcoRII restriction endonuclease gene （ecoRIIR） and methyltransferase gene （ecoRIIM） in one vector and to analyze the coordinating expression of this whole R M system.Methods. Unidirectional deletion subclones were constructed with ExoIII.ecoRIIR/M genes were preliminarily located in the cloned fragment according to the enzyme activities of subclones. Exact deletion sites were determined by sequencing, and transcriptional start sites were determined by S1 mapping. Results. The DNA fragment which was cloned into pBluescript SK+contained intact ecoRIIR gene andecoRIIM gene, and two transcriptional start sites of ecoRIIR gene were determined. 132bp to 458bp from 3’end of ecoRIIR gene are indispensable to enzyme activities and deletion of 202bp from 3’end of ecoRIIM gene made enzyme lose the capability in DNA protection to resist specific cut with EcoRII endonuclease （EcoRII.R）. Deletion of the coding and flanking sequences of one gene did not affect the expression of the other gene, and the recombinants only containing ecoRIIR gene appeared to be lethal to dcm+host. Conclusion. ecoRIIM gene linking closely to ecoRIIR gene is very important for the existence of the R M system in process of evolution, but the key tocontrol EcoRII R M order may not exist in transcriptional level .Keywords：EcoRII endonuclease;EcoRII methylase;deletion mutation;gene expression4|9|0Updated：2024-04-10
- Abstract：Objectives. In an attempt to develop new method of treating the end ormid stage pancreatic cancer, we examined the effect of ischemic re perfusion injury plus particle embolism on the pathology and cell apoptosis of pancreatic cancer in Sprague Dawely rats. Methods. 9 mg dimethylbeneanthracine （DMBA） were implanted directly into the parenchyma of pancreatic tail of Sprague Dawely rats. After establishment of tumor, the inferior splenic artery, a main supplying vessel to pancreatic tail was subjected to blockade and re opening for 30 min separately, then embolism particles were infused via the artery. Afterwards, artery was ligated. Pathological changes and cell apoptosis indicators （AI） of pancreatic cancer were observed by light microscopy and ISEL respectively 14 days after the operation. Results. The prevalence of pancreatic cancer among DMBA implanted rats evaluated 3 months to 4 months after implantation was 59%. The volumes of the tumor in positive control group （B）, pancreatic ischemic group （C）, pancreatic ischemic re perfusion injury group （D） were significantly larger than pancreatic ischemic re perfusion injury plus particle thrombus group （E） （P< 0.01）. Thevolumes of the tumor in groups D, E were significantly smaller than that in group C （P< 0.01）. There was a significant difference in tumor size between group Band group C （P< 0.01）, but the difference was not significant between group D and group E （P >0.05）. There was a significant infiltration of tumor tissue in group B rats, but strong inflammatory reaction was not noted. In groups C, D, E, alocalized tumor growth was observed; infiltration of inflammatory cells and proliferation of fibroblasts and connective fiber were obvious, and some of these fibers grew into cancer nests and separate the tumor. The above findings were most conspicuous in group E. There was a significant difference in AI between group E （13.7±1.5）and other groups （P< 0.01）, with the difference being also significant between group C（4.3±2.4）, D （8.5±1.1）and group B （1.2±0.8）（P< 0.01）, and between group C and group D （P< 0.01） or between group D and group E （P< 0.01）. In the samples of group A, the apoptotic cells were not found. Conclusions. Pancreatic ischemic re perfusion injury plus particle thrombus can cause significant infiltration of inflammatory cells in tumor tissues thereby limiting its growth, and inducing cell apoptosis of pancreatic cancer. This effect is superior to either pancreatic ischemia alone or pancreatic ischemia plus re perfusion injury.Keywords：pancreatic cancer;ischemia re perfusion;apoptosis4|7|2Updated：2024-04-10
- Abstract：Objective. To study the characteristics and pathogenesis of gut barrier damage following multiple firearm injuries in a porcine model. Methods. Twenty four small pigs were divided into 4 groups: control group （n=6, group C）, group H （n=6, gunshot induced tangential fracture of parietal bone）, group L （n=6, gunshot induced comminuted fracture of bilateral femora） and group M （n=6, combined group H+L）. Gastric intramucosal pH （pHi）, plasma endotoxin levels in portal vein, and plasma D lactate levels were measured and blood samples were cultured at different intervals after trauma. The animals were sacrificed at 72 h following trauma and intestinal tissues were harvested for pathological examination and diamine oxidase （DAO） activity measurement. Results. In group M at 72 h, pHi was significantly lower than that of group H and L （P< 0.01）, and plasma endotoxin level was significantly higher than that of group H （P< 0.01） and group L （P< 0.05）. Simultaneously, in groupM, D lactate level was markedly higher than that of group H （P< 0.01）, and incidence of positive blood culture was much higher than that of group H and L （P<0.05）. Necrosis and exfoliation were revealed at ileum villus top in all traumagroups, especially in group M, in which ileum DAO activity declined most significantly as well. Conclusion. Multiple trauma is prone to cause gastrointestinal ischemia even without hemorrhagic shock. The damage of gut barrier in multiple trauma appears to be more severe than that in one site trauma, thereby promoting gut derived endotoxemia and bacterial translocation and contributing to the development of endogenous infection.SURGICAL TREATMENT OF MALIGNANTESOPHAGEAL TUMORS IN PUMC HOSPITAL Guo Huiqin,Li Zejian ,Zhang Fan1 ,Zhang Zhiyong,Xu Letian ,Li Weidong2,Wang Xiuqin2and Wu Min2Department of Thoracic Surgery, PUMC Hospital, CAMS &PUMC, Beijing 100730Key words malignant esophageal tumors; early diagnosis; FHIT geneTo study how to prolong the postoperative survival time of the patientswith malignant esophageal tumors. The clinical data of 1098 patients with malignant esophageal tumors from 1961 to 1992 were retrospectively analyzed. The deletion of fragile histamine triplet （FHIT） gene （a tumor suppressor gene） in 30 fresh esophageal samples obtained in 1996 was detected with PCR and RT PCR method. The resectability was raised gradually and the operative morbidity and mortality decreased year by year, but there was no significant improvement on the postoperative 5 year survival rate. Delayed diagnosis and irradical resection influenced the long term survival. The deletion of cDNA of FHIT gene was 64.2%in esophageal cancer and 20%in the resected margin of the cancer. We believe that high grade atypical hyperplasia in esophageal epithelium and deletion of FHIT gene in esophageal cancer and its resected margin are pathological and molecular markers for early diagnosis of esophageal cancer respectively, and the latter may be one of the molecular markers for the resection. Early diagnosis and treatment, radical resection, and postoperative nutritional support are very important for the improvement of the postoperative survival time of the patients.Keywords：small pig;multiple firearm injuries;gut barrier function;bacterial/ endotoxin translocation4|13|0Updated：2024-04-10
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- Abstract：To study how to prolong the postoperative survival time of the patients with malignant esophageal tumors. The clinical data of 1098 patients with malignant esophageal tumors from 1961 to 1992 were retrospectively analyzed. The deletion of fragile histamine triplet （FHIT） gene （a tumor suppressor gene） in 30 fresh esophageal samples obtained in 1996 was detected with PCR and RT PCR method. The resectability was raised gradually and the operative morbidity and mortality decreased year by year, but there was no significant improvement on the postoperative 5 year survival rate. Delayed diagnosis and irradical resection influenced the long term survival. The deletion of cDNA of FHIT gene was 64.2% in esophageal cancer and 20% in the resected margin of the cancer. We believe that high grade atypical hyperplasia in esophageal epithelium and deletion of FHIT gene in esophageal cancer and its resected margin are pathological and molecular markers for early diagnosis of esophageal cancer respectively, and the latter may be one of the molecular markers for the resection. Early diagnosis and treatment, radical resection, and postoperative nutritional support are very important for the improvement of the postoperative survival time of the patients.Keywords：malignant esophageal tumors;early diagnosis;FHIT gene4|13|0Updated：2024-04-10
- Abstract：Objective. To explore an effective method of surgical management of craniopharyngioma. Subjects and methods. Fifty patients with craniopharyngioma had total andsubtotal tumor ectomy. There were 29 males and 21 females, ranging in age from 15 to 56 years （mean 34.1 years）. MR imaging showed that the tumors were locatedin the superior sellar region in 24 cases, in superior sella region and extended into the third ventricular floor in 19 cases, into parasella in 3 cases and down to intrasella in 4 cases. Complete cystic tumors were found in 5 cases, whilethe partial cystic tumor in 24 cases and complete solid tumors in 21 cases. Pterional approach was used in 48 patients and subfrontal approach in 2 patients. Great attention was paid to the preservation of the perforating arteries from thecarotid, posterior and anterior communicating and anterior choroidal arteries to the hypothalamic structures. The clinical outcome was evaluated according to the GOS scale.Results. Of the 50 patients surgically treated, 47 patients obtained total ectomy of the tumor and 3 patients with the secondary surgery had subtotal ectomy of the tumor. The pituitary stalk was preserved in 29（58%） patients, severed in 14 patients and unidentified in 7 patients. Forty-six patients regained a normal life; one patient needed assist in life. Of the 3 deaths, one patient died of diabetes insipidus, one of inhalation asphyxia, and another one of water and sodium disorders. Conclusion. Avoidance of the injury to the neural structures in the thirdventricular floor and preservation of the perforating arteries to hypothalamus are the key to achieve good surgical results in treating craniopharyngioma.Keywords：craniopharyngioma;perforating artery;surgical removal;hypothalamic structures4|21|0Updated：2024-04-10
- Abstract：Objective . To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat （BB 94） on mouse forestomach carcinoma （MFC）, and compared them with doxorubicin. Methods and results. In vitro, growth curve analysis, MTT assay and clonogenic assay used to determine the cytotoxic effect of docetaxel or/and BB 94 on MFC cell showed that docetaxel but not BB 94 had a significant cytotoxicity, and the effect of docetaxel wasn’t enhanced by BB 94. In early stage MFC tumor model, obvious antitumor effect of docetaxel or doxorubicin given i.v. at maximum tolerated dose （MTD, docetaxel: 20mg/kg; doxorubicin: 6mg/kg） every 4 days for 3 injections （q4d×3）, even that of BB 94 （30mg/kg i.p. qd×20） was observed. Tumor growth inhibition was greater for docetaxel batimastat （96.0%） than for doxorubicin-batimastat （88.0%）, docetaxel （89.0%）, doxorubicin （68.0%） and BB 94 （33.0%）, and the effect of docetaxel could be potentiated by BB 94. Docetaxel also showed activity against advanced stage MFC tumor in dose-dependent manner, and was more effective at MTD than doxorubicin with 4/5 regressions, 46.5 days tumor growth delay and 2.8log10 tumor cell kill. Conclusion. Our results suggest that in the MFC model with dose and schedule used, docetaxel is an effective cytotoxic new drug against MFC tumor and BB 94 enchances the antitumor activity of docetaxel.Keywords：docetaxel;batimastat;stomach neoplasms;combined modality therapy4|19|3Updated：2024-04-10
- Abstract：Objective. To investigate the unique characteristics and treatment of thoracic spine fractures. Methods. Seventy seven patients with thoracic spine fractures were retrospectively reviewed. Of these, there were 37 compression fractures, 34 fracture dislocations, 3 burst fractures and 3 burst dislocations. Twenty six patients had a complete lesion of the spinal cord, 14 sustained a neurologically incomplete injury, and 37 were neurologically intact. Fifty three patients were treated nonoperatively and 24 treated operatively. Results. All patients were followed up for 2～15 years. None of the 26 patients with a complete lesion recovered any significant function. Of 37 neurologically intact patients, 13 had local pain although all of them remained normal function. Two of 14 patients with incomplete paraplegia returned to normal, 7 recovered some function and 5 did not recovered. Conclusions. Because of the unique anatomy and biomechanics of the thoracic spine, the classification commonly applied to thoracolumbar fractures is not suitable for thoracic fractures. Fusion and instrumentation are indicated when the fractures are unstable, while patients with incomplete lesion of the spinal cord may be the candidates for supplemented decompression.Keywords：thoracic spine;fractures;spinal cord injuries4|19|1Updated：2024-04-10
- Abstract：Objective. To investigate the characteristics of urotensin II （U II） receptor in the rat airway smooth muscle and the effect and signal transduction pathway of U II on the proliferation of airway smooth muscle cells. Methods. Using 125I UII binding assay to measure the Bmax and Kd of U II receptor. Using the 3H TdR incorporation to determine the effect of U II on the proliferation of airway smooth muscle cells and its signal transduction pathway. Using Fura 2/AM to measure the effect of U II on the cytosolic free calcium concentration. Results. 1. 125I UII binding increased with the time and reached saturation at 45min. The Bmax was （11.36±0.37）fmol/mg pr and Kd was （4.46±0.61）nmol/L. 2. U II increased 3H TdR incorporation of the airway smooth muscle cells in a dose dependent manner. 3. H7, PD98059 and nicardipine, inhibitors of PKC, MAPK, calcium channel, respectively, significantly inhibited U II stimulated 3H TdR incorporation of airway smooth muscle cells. W7, inhibitor of CaM PK, had no effect. 4. Cyclosporin A, inhibitor of CaN, inhibited 3H TdR incorporation of the airway smooth muscle cells induced by U II in a dose dependent manner. 5. U II promoted cytosolic free calcium concentration increase by 18%. Conclusions. 1. There was U II receptor in the rat airway smooth muscle. 2. The effect of U II stimulated 3H TdR incorporation of airway smooth muscle cells was mediated by such signal transduction pathway as Ca2+, PKC, MAPK and CaN, etc.Keywords：urotensin II;airway smooth muscle;signal transduction4|30|1Updated：2024-04-10
- Abstract：Objective. To evaluate the diagnostic criteria for the localization of acquired arteriovenous fistulas （AVFs） by color Doppler flow imaging （CDFI） based on the features of their hemodynamic changes. Methods. The shape and hemodynamic changes of involved vessels which could be helpful to localize the sites of fistulas were studied according to the observation of 10 cases of acquired AVFs. Results. The sites of the fistulas could be shown by two dimensional ultrasonography and color flow imaging in 40%and 80%cases, respectively. In all cases, turbulent high velocity flow was present at the sites of the fistulas, low resistant flow was present in the arteries proximal to the fistulas, and artery like flow was detected in the veins. Conclusion. CDFI was accurate for the localization of acquired AVFs, which were mainly localized by their hemodynamic changes shown by pulse Doppler ultrasound.Keywords：arteriovenous fistula;ultrasonography;Doppler4|23|0Updated：2024-04-10
- Abstract：Objective. To investigate the treatment of corneal epithelial ingrowth with flap melt after LASIK. Patients and method. Thirteen eyes of 13 patients with corneal epithelial ingrowth and flap melt after LASIK were treated based on the thickness and the extent of melting of the flap. Nine eyes were treated by lifting the flap and scraping the epithelium in the interface. Three eyes underwent allogenic keratomileusis. The flap was removed in one eye. Results. Recurrence occurred in 2 eyes treated by lifting the flap. The flaps, however, healed normally after retreatment. The grafts healed normally in the allogenic keratomileusis group, except for one eye in which the flap was lost. The corneal epithelium healed over the stromal bed after the flap was removed. Corneal haze of grade 2 was present at 6 months. The uncorrected visual acuity was between 0.3 and 1.0, and the best corrected visual acuity lost 1 to 3 lines. Conclusions. Corneal epithelial ingrowth with flap melt is a severe complication after LASIK. However, with proper treatment, vision can be salvaged in most cases.Keywords：refractive surgery;cornea;epithelial ingrowth;laser4|9|1Updated：2024-04-10
- Abstract：Objective. To discover the relation between alkaline phosphatase （ALP） in gingival crevicular fluid （GCF） of implant teeth and the curing results. Methods. We measured the ALP level in GCF among 56 cases of implant teeth which included 2 failed cases, 5 cases with bad oral hygiene and gingivitis, and compared it with that in the normal group composed of 10 persons. Results. The ALP levels in normal group and success implant group showed no difference. The ALP levels in normal group and success with gingivitis group showed obvious difference. The ALP levels of the 2 failed cases are the highest of all.Conclusions. The ALP level in GCF is an important index in evaluating the curing result of the implant teeth.Keywords：implant teeth;gingival crevicular fluid;alkaline phosphatase4|7|2Updated：2024-04-10
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