Volume 112  ·   Issue 01  ·  1999

OBJECTIVE To evaluate the newly developed perfluoropropene-filled echo-contrast agent (FCT-188) in non-invasive assessment of risk areas (RA) and infarct areas (IA) with intravenous myocardial contrast echocardiography (MCE) in canine model of ischemia followed by reperfusion. METHODS Eight chest-opened Beagle dogs with a 90-minute ischemia followed by a 240-minute reperfusion were studied. MCE was performed after a bolus injection of FCT-188 (0.025 ml/kg, Ⅳ) into a superficial vein of the forelimb at baseline, 20 minutes after occlusion, and 4 h after reperfusion to non-invasively assess the left ventricular myocardium area (LVMA), myocardial ischemic risk area (RA), and infarct area (IA) in a short-axis view of left ventricle. The accuracy of detecting myocardial perfusion with intravenous MCE was further assessed by in vitro myocardial staining of the matched cross-sections. Both RA and IA were expressed as percent of LVMA. RESULTS LVMA, RA, IA, and IA/RA ratio were accurately assessed by MCE (LVMA: 6.60 cm2±0.76 cm2; RA: 35.7%±6.68%; IA: 21.0%±13.2%; IA/RA: 60.3%±31.4%; n=7) as compared with those of the matched cross-section (LVMA: 6.81 cm2±0.73 cm2, P=0.062; RA: 35.3%±9.9%, P=0.84; IA: 25.10%±14.5%, P=0.07; IA/RA: 68.0%±22.2%, P=0.28, respectively). There was a significant correlation of MCE-assessed IA/RA ratio and its corresponding pathologiclly determined finding in vitro (Y=1.21X-21.6, r=0.73, P=0.015). No significant changes of electrocardiogram (ECG), mean artery pressures (MAP), pulmonary artery pressures (PAP), and pulmonary artery wedge pressures (PAWP) were found between pre- and post-intravenous injection of FCT-188 at each time point. Conclusion These indicate that FCT-188 can be used to assess risk areas and infarct areas accurately and non-invasively with intravenous MCE in the canine model of a 90-minute ischemia followed by a 240-minute reperfusion and might have potential significance for non-invasive assessment of myocardial reperfusion clinically.

OBJECTIVE To evaluate the possible relationship between insulin-like growth factor-1 (IGF-1) and diabetic neuropathy (DNP). METHODS Sixty-nine patients with Type 2 non-insulin-dependent diabetes (54 with peripheral neuropathy and 15 without neuropathy) were observed. Normal controls were 34 non-diabetic persons. Diabetic peripheral neuropathy diagnosis was carried out taking into account results of NS, ND, NC and AF. After an overnight fast, blood was taken for IGF-1, glucose, hemoglobin Alc, C-peptide, and insulin. Plasma IGF-1 was measured by radioimmunoassay (RIA) method. RESULTS The neuropathic group had significantly lower levels for IGF-1 (86.43 ng/ml ±45.18 ng/ml) compared to normal controls (119.68 ng/ml ±89.42 ng/ml) (P<0.05), and to diabetic patients without neuropathy (113.75 ng/ml ±66.58 ng/ml) (P<0.05). No significant difference was found between diabetic non-neuropathic group and normal control subjects (P>0.05). In diabetic subjects there was a positive correlation (γ=0.27, P<0.05) between IGF-1 and beat to variation in heart rate. There were negative correlation bwteen IGF-1 and postprandial blood glucose (γ=-0.3, P<0.05), and aspartic acid translocase (γ=-0.27, P<0.05). Conclusio In diabetic patients with peripheral neuropathy there are abnormalities of IGF-1 that may contribute to the pathogeneses of diabetic neuropathy.

OBJECTIVE s　To identify possible mutations in our previously cloned candidate gene for hereditary multiple exostoses type Ⅱ (EXT2) in affected members of EXT families so as to confirm that it is the disease-causing gene. METHODS The mutation was detected first by single strand conformational polymorphism(SSCP) of all coding exons of the candidate gene and then by sequencing analysis. RESULTS After analyzing 37 patients from 20 Chinese EXT families by SSCP and DNA sequencing analysis, one 2-bp insertion mutation was identified in this candidate gene in affected members of an EXT family. This mutation resulted in the frameshift and generated a truncated gene product consisting of 105 amino acids. CONCLUSIONS The identification of the mutation in the candidate gene indicates that this novel gene is responsible for EXT2 (one of the disease-causing gene of EXT).

OBJECTIVE To investigate cloning and expression of β2-glycoprotein 1 (β2GP1) recognized by antiphospholipid antibodies and to study the clinical significance of anti-β2GP1 antibodies in patients with autoimmune disease. METHODS By using reverse transcription-PCR method, two kinds of expression plasmid which expressed β2GP1 and the fifth domain of β2-glycoprotein 1 (β2GP1-D5) proteins respectively were constructed in this study. Their antigenic activities were identified by immunoblots using rabbit anti-β2GP1 antibodies. Anti-rβ2GP1 and anti-rβ2GP1-D5 antibodies in the 112 patents were detected by ELISA using rβ2GP1 and rβ2GP1-D5 as coating antigens. RESULTS A significant correlation in statistics (r=0.667, P&lt;0.01) between the levels of anti-rβ2GP1 and anticardiolipin antibodies (aCL) was found. The presence of anti-rβ2GP1 antibodies was associated with an increased frequency of history of thrombosis and/or recurrent abortion. Anti-rβ2GP1 assay provided better specificity than conventional aCL assay. The binding of anti-rβ2GP1 from the sera of patients with antiphospholipid syndrome (APS) to rβ2GP1 was inhibited by rβ2GP1-D5. Meanwhile, of 28 patients who had positive anti-rβ2GP1 antibodies in sera, 27 (96.4%) had positive anti-rβ2GP1-D5 antibodies. Conclusion It is indicated that antigenic epitope of β2GP1 might be located in its fifth domain. Detection of anti-rβ2GP1 antibodies may be of potential value for evaluating the risk of thrombosis and/or other APS associated symptom.

OBJECTIVE To detect expression of intercellular adhesion molecule-1 (ICAM-1), B7.1 and thyroid peroxidase (TPO) on thyrocyte and study the possible mechanism of interferon-alpha (IFN-α) in the pathogenesis of autoimmune thyroid disease (AITD). METHODS Thyrocytes were cultured from 6 normal persons. Antigen expression on thyrocytes induced by cytokines was examined using immunofluorescence staining with flow cytometer. RESULTS IFN-α significantly stimulated the expression of ICAM-1, B7.1 and TPO, as compared with those of control group. IFN-γ markedly enhanced the expression of HLA-DR and ICAM-1, but not B7.1. Prolactin (PRL) resulted in increased expression of ICAM-1, B7.1, as well as overexpression of TPO, which is more significant than that stimulated by IFN-α. CONCLUSIONS Thyroid autoimmunity induced by IFN-α is associated with the expression of ICAM-1, B7.1 and TPO. IFN-γ could not induce the expression of B7.1, therefore it is not an initiator in AITD. In addition, we should pay more attention to PRL which possibly plays an important role in the initiation and perpetuation of postpartum thyroiditis.

OBJECTIVE To evaluate the functional and morphologic features of stomach in liver cirrhosis model and the cytoprotective effects of Vitamin E. METHODS Experimental cirrhosis was induced in rats by subcutaneous administration of 0.4 ml CCl4 (diluted 1∶4 with olive oil) per kilogram of body weight twice a week for 12 weeks. Rats were divided into three groups. Group 1 was control. Group 2 consisted cirrhotic rats induced by CCl4 and Group 3 cirrhotic rats treated with Vitamin E (intramuscularly 100 mg/kg per day during study). At the end of 12 weeks, gastric mucosal injury was produced by instillation of absolute alcohol via an orogastric tube. After 3 hours, each animal was sacrificed. The stomachs were macroscopically, microscopically and biochemically analyzed. RESULTS Macroscopic and microscopic area of gastric mucosal injury were significantly larger in cirrhotic rats (P<0.05). Gastric mucosal injury was more serious in cirrhotic rats as compared with Group 1. With vitamin E treatment, tissue Malondialdehyde (MDA) and glutathione ［GSH (X)］ levels were significantly lower in group 3 as compared with group 2 (P<0.001). Conclusion Gastric mucosa in cirrhotic rats has distinctive histological and functional abnormalities. These abnormalities can be reversed by Vitamin E or other antioxidants.

Objective To evaluate the killing effect of interleukin-2 (IL-2) and interferon-α (INF-α) activated bone marrow cells on K562 cells. Methods Semi-solid colony and 3H-TdR incorporating method were used. Results Bone marrow from leukemia patients in remission was activated in vitro with IL-2 for 3 days. The activated bone marrow (ABM) displayed killing effects of 0.31-2.30 logs on K562 cells. This killing effect was further increased to 0.30-3.15 logs when INF-α added with IL-2 to the marrow for activation. IL-2 alone or in combination with IFN-α showed no inhibition of CFU-GM and K562 cells. Compared with IL-2 or IFN-α alone, the combination of the two cytokines could more effectively maintain the killing effect of ABM on leukemic cells. Conclusion IFN-α can augment the purging effect of IL-2 ABM and combination of the two cytokines can effectively maintain the cytotoxicity of ABM.

OBJECTIVE To hibernate fetal ventral mesencephalic tegmental (VMT) cells from Spraque-Dawley rats E-15 for 5 days at 4℃ in either hibernation media (HM) or in conditioned hibernation media (CHM) supplemented with trophic factors such as epidermal growth factor (EGF 200 ng/ml), basic fibroblast growth factor (bFGF 100 ng/ml), recombinant human brain derived neurotrophic factor (rhBDNF 20 μg/ml), recombinant human glial cell-derived neurotrophic factor (rhGDNF 20 μg/ml), fetal calf serum (FCS 9%), or human placental cord serum (HPCS 10%). METHODS The percent of cell viability and the density of tyrosine hydroxylase immunoreactive (THir) cells in fetal striatal-VMT co-culture were determined. RESULTS The viability of fetal striatal cells (0.8±0.104) was slightly higher than that of fetal VMT cells (0.7±0.072) at 0-time point (F17,1=4.677; P=0.045). After 5 days of hibernation, the viability of fetal VMT cells reduced by 30% (F7,1=88.493; P<0.001) in HM. However, THir-cell density reduced by more than 90% as compared to the freshly harvested VMT cells (F7,1=179.944; P<0.001). CHM with HPCS, bFGF, EGF, BDNF, and GDNF showed higher THir-cell density than that of HM or CHM supplemented with FCS (P<0.001). Conclusion Supplementation of appropriate trophic factors for hibernated fetal VMT cells promotes cell viability and the subsequent expression of Thir-cell density.

OBJECTIVES To get a more comprehensive recognition about carpal tunnel syndrome (CTS), especially the manual housework as its risk factor, and to facilitate early diagnosis and proper treatment. METHODS 262 CTS patients (396 CTS hands) were analyzed retrospectively. A 1∶1 matched case-control study of 61 woman pairs in relationship between manual housework and the occurrence of CTS was carried out. RESULTS In 262 CTS patients, 84% were female, and the dominant hand was more frequently affected; repetitive and forceful movement of the hand and wrist might be associated with CTS. Typical clinical manifestations include pain and paresthesia in the median nerve territory, but 75.3% of our 396 CTS hands had all five digits involved. Conduction abnormalities appeared selectively in the median nerve distal to the wrist. In the case-control study, for manual washing, rolling or kneading dough, and knitting woolen sweater, the odds ratios (OR) of CTS between high and low intensities were 3.86 (95% confidence interval 1.79-8.33, χ2=11.76, P<0.01), 6.25 (95% confidence interval 2.50-15.63, χ2=15.21, P<0.01) and 1.13 (95% confidence interval 0.57-2.22, χ2=0.125, P>0.05) respectively; and those between long and short duration (i.e. the number of years engaging in these manual housework) were 2.33 (95% confidence interval 0.63-8.64, χ2=1.6, P>0.05), 1.88 (95% confidence interval 0.81-4.38, χ2=2.13, P>0.05) and 1 (χ2=0, P>0.05). CONCLUSIONS The diagnosis of CTS requires confirmation of illness history, symptoms and signs with objective electrodiagnostic tests. Manual washing and rolling or kneading dough might be associated with the onset of CTS.

Objective To investigate the relationship between c-jun mRNA and apoptosis of neurons following perinatal ischemic-hypoxia. Methods We set up a fetal rat model of perinatal ischemic-hypoxia by ligating unilateral uterine horn vessel of pregnant Wistar rats (21-day gestation). The contralateral horn vessel was not ligated and the fetuses in these uteri served as controls. Rat pups were delivered by cesarean section at the end of ischemic hypoxic insult and then the rats’ brain tissues were collected in different points of time. In situ hybridization and TUNEL methods were used to detect the c-jun mRNA expression and neural cells apoptosis separately. Results The expression of c-jun mRNA in brain tissues began at 15 minutes, reached the first peak at 1-2 hours after ischemic-hypoxic insult and reduced gradually after 4 hours and the second peak at 24th hour after insult, gradually disappeared till 72nd hour. There were very low c-jun mRNA expression of hippocampus in the control group 24 h after birth. Meanwhile, we observed that the apoptosis of neuronal cells in cerebral cortex was much more than that in the control group. Conclusion The increases of immediate early gene c-jun expression and the cell apoptosis could be induced by perinatal ischemic-hypoxia. The higher expression of c-jun mRNA might induce the transcription of its target gene, especially, so called “death related genes”, which would be a promoter for cell apoptosis.

Purpose To document and review all the published reports on smoking and coronary heart disease (CHD) in China and Hong Kong, and to estimate the risks of CHD due to smoking. Data sources Papers cited in Medline, Chinese Biomedical Literature Disc and Chinese Medical Current Contents, references in review papers, conference papers and abstracts. Study selection All published reports which had findings on smoking and CHD were included.|Data extraction|Reports on 13 cross-sectional, 16 case-control and 13 prospective studies were included. Available data on risk estimates from 23 studies were extracted and pooled odds ratios (OR) and relative risks (RR) were calculated using Mantel-Haenszel’s methods. Results In China in 1970s, most results, which were from cross-sectional studies, did not show an association between smoking and CHD. In the 1980s, most case control studies found an association but the prospective studies did not. In the 1990s, there was stronger evidence from prospective studies mainly in men. The relative risk was about 1.90 in men and about 2.50-3.50 in women although the 95% confidence interval for the latter was wide. Dose response relationships were observed in 12 studies. In Hong Kong, there were one cross-sectional and two case control studies. Conclusions The existing evidence supports that smoking is a cause of CHD in Chinese, particularly in men. More data in women are needed to quantify the risk more precisely. The risk estimates probably indicate only the early stage of a growing tobacco epidemic.

This short review summarizes an integrated approach to new methods of managing hepatocellular carcinoma (HCC) developed at our centre. HCC-specific isoforms of alpha-fetoprotein were detected by isoelectric focusing and their value in the differential diagnosis of early HCC on a background of chronic liver disease has been shown. Selective internal radiation therapy using yttrium-90 (90 Y) microspheres has been shown to be an effective treatment for inoperable HCC in a phase Ⅰ and Ⅱ study. A partition model for estimating the radiation doses from the　90 Y microspheres to the tumour and the non-tumorous liver during the therapy was then formulated, verified by correlating with intraoperative dosimetry, and evaluated in clinical settings. This permits　90 Y microspheres to be administered safely without the need of an open surgery and a randomized therapeutic controlled trial is in progress. Another radomized controlled trial using iodine-131 Lipiodol as a post-operative adjuvant therapy, aiming at reducing the recurrence rate is also on-going. HCC may be more effectively combated with a better understanding of its pathogenesis from chronic liver disease.