The variable heavy chain region (VH) genes of 3 untreated patients with B-cell chronic lymphocytic leukemia (B-CLL) were cloned and analyzed. The VH family used was VH3-11, VH3-72 and VH3-33. More than 2% difference from the corresponding germline gene was detected in all the 3 obtained potential functional genes (average 16.7). Mutation pattern analysis indicated evidence of antigen selective pressure observed in 1 of 3 cases. Our findings suggested that the tumor cells originate from post-GC cells.
The luminous intensity of dark variant (S1) separated from photobacterium phosphoreum (A2) was 1/10 000 less than that of wild-type. Ethidium bromide (EB) (0.6 mg/L), Mytomycin C (MC, 0.05 mg/L), 2-amino fluorene (2-AF, 1.0 mg/L) all could strongly induce reversion mutation for S1 within 24 h and increase reversion ratio significantly. The results of experiments indicated that these revertants had stable genetic characteristic and the mutation may take place at gene levels. The mutagenesis to S1 caused by EB, MC and 2-AF was detected and it may be used as a new rapid, simple and sensitive method for gene toxicant monitoring.
In order to study the role of annexin II, a recombinant expression vector, pZeoSV2 (+)ANN II, containing the annexin II cDNA, was developed. The 1. 1-kb-length annexin II cDNA was inserted into a expression vector, PZeoSV(+) and transfected into HL-60 cells which had low baseline expression of Ann- II. pZeoSV(+) ANN II was analyzed by restriction mapping and the Ann- II sequence identified. The ability of the transfected cells, non-transfected and mock-transfected cells to stimulate t-PA-depend plasminogen activation was compared. The results showed that HL-60 with pZeoSV(+) ANN II transfection could significantly increase the plasminogen activation (8.9±1.2 U)in vitro with the difference being significant as compared with non-transfected (1.5±0.4 U) and mock-transfected cells (4.2±0.9 U), respectively. Antiannexin II oligonucleotides significantly inhibited the binding ability of t-PA and plasminogen to annexin II, and obviously reduced the plasminogen activationin vitro. The above findings showed human umbilical vein endothelial cells (HUVECs) treated with sense or missense oligonucleotides indicated no significant change in binding of t-PA and PLG. Treatment of HUVECs with antiannexin II oligonucleotides could significantly reduce the plasminogen activation by 2.4–0.3 U as compared with sense oligonucleotide group in binding of t-PA and PLG. These results, therefore, suggest that Ann- II can bind plasminogen and participate in the stimulation of t-PA-dependent activation of plasminogen, and that interference with Ann- II mRNA by antisense oligonucleotide may be a new strategy for the therapy of bleeding in patients with hyperfibrinolysis.
In order to regulate the apoptosis induced by Fas-FasL system, a soluble isoform of mouse Fas was cloned from thymocytes of immature mice with the primers designed according to the full-length Fas cDNA sequence in the GeneBank. It was directionally inserted into the intermedium vector pUC19. DNA sequencing proved that it was consistent with the expected sequence. Then it was subcloned into the eukaryotic expression vector pCA13, which was used to construct the recombinant vector pCA13-FasC. By lipofectamine (LF2000)-mediated transfection, pCA13-FasC was transfected into the 293 cells. RT-PCR and Western blot indicated that the murine soluble Fas C protein was expressed in the 293 cells. Apoptosis inducing test showed that the expression of this murine Fas C could block the Fas-induced apoptosis, which confirmed the biological activity of the recombinant Fas C.
To explore the effects of platelet factor 4 (PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplanation (BMT). The syngenic BMT mice models were established. 20 and 26 h before irradiation, the mice were injected 20 μg/kg PF4 or PBS twice into abdominal cavity, then the donor bone marrow nuclear cells (BMNC) were transplanted. On the 7th day, spleen clone forming units (CFU-S) were counted. On the 7th, 14th and 21st day after BMT, the BMNC and megakaryoryocytes in bone marrow tissue were counted and the percentage of hematopoietic tissue and expression level of heparan sulfate in bone marrow tissue were assessed. In PF4-treated groups, the CFU-S counts on the 7th day were higher than those in BMT groups after BMT. The BMNC and megakaryoryocyte counts and the percentage of hematopoietic tissue and heparan sulfate expression level were higher than those in BMT group on the 7th, 14th and 21st day after BMT (P<0.01 orP<0.05). PF4 could accelerate hematopoietic reconstitution of syngenic bone marrow transplantation. The promotion of the heparan sulfate expression in bone marrow may be one of mechanisms of PF4.
Silencing ATM gene gave rise to enhanced apoptotic response to irradiation and irradiation-like chemotherapy agents, this paper explored the crucial identities of the molecular elements responsible for the enhanced apoptotic response in U937 cells mediated by silencing ATM gene. Two U937 cell mutants named U937-ASPI3K (ATM, negative) and U937-pZeosv2(+) (ATM, wild-type) were used as a cell model system to identify the critical molecule(s) responsible for the varied apoptotic response in the absence or presence of ATM gene. Apoptosis was examined by measuring concentrations of free nucleosome in U937 cells. Western blot was employed to measure nuclear protein abundance of CDC25A, CDC25B, CDC25C, total p34cdc2, p34cdc2 (Thr 161) or p34cdc2 (Thr 14, Tyr 15). RT-PCR was used to estimate CDC25 transcript levels. U937-ASPI3K exhibited an enhanced apoptotic response to lower dosage of irradiation, which could not be blocked by protein synthesis inhibitor. Protein serine-threonine phosphatase inhibitor or cyclin-dependent kinase (CDK) inhibitors, on the other hand, abolished the enhancement indicated that protein phosphorylation/dephosphorylation modification and CDK activity are required for the enhanced apoptotic response in the absence of ATM gene. Upon irradiation, p34cdc2 in U937-pZeosv2 (+) was maintained in an inactive state by phosphorylation on threonine 14 (Thr 14) and tyrosine 15 (Tyr 15), which was associated with a dramatic decrease of nuclear CDC25A, CDC25B and CDC25C proteins. In contrast, p34cdc2 in U937-ASPI3K maintained in an active state by dephosphorylation on threonine 14 (Thr 14) and tyrosine 15 (Tyr 15), which was associated with constant nuclear CDC25A, CDC25B and CDC25C protein abundance before and after irradiation. The responsive decrease of nuclear CDC25 proteins occurred at the post-transcription level. Silencing ATM gene blocks the responsive decrease of nuclear CDC25 proteins, which is responsible for failure to inactivate p34cdc2 after irradiation. Active p34cdc2 and CDK2, in turn, acts as the death executors to trigger apoptosis. In summary, aberrantly activated CDK activity is the critical molecular mechanism central to enhanced apoptotic responses in the absence of ATM gene.
To assess the value of CD34+ cells transferred exogenous Fas ligand (FasL) in inducing apoptosis of human leukemic cells, the CD34+ cells transfected with FasL or without, pretreated with mitomycin C, was mixed with leukemic cell line U937 cells in presence or absence of daunorubicin (DNR) or cytosine arabinoside (Ara-C). After 18 h, apoptosis of cells was detected by FCM and TUNEL. Induced for 18 h by CD34+ cells transfected with FasL or without, the ratio of apoptosis of U937 cells was (5.0±1.3)%, (10.8±0.6)% (P<0.01), respectively. Induced by FasL+CD34++DNR, FasL+CD34++Ara-C, the ratio was (13.4±1.0) % (P<0.05), (17.9±1.3)% (P<0.01), respectively. The result demonstrated that CD34+ cells transfected with exogenous FasL could induce apoptosis of human leukemic cells and showed a cytotoxic synergistic effect when used in combination with chemotherapeutic drugs, suggesting that it was possible to develop a new method in treatment of leukemia.
To investigate the effects of Ligustrazine on histogenesis of bone marrow in the early phase of hematopoietic reconstruction in bone marrow transplantation (BMT) mice. The syngeneic BMT mice model was established. The syngeneic BMT mice were orally given 2 mg Ligustrazine twice a day. 1, 3, 5, 7, 10, 15 and 21 day(s) after BMT, peripheral blood granulocytes and bone marrow nucleated cells (BMNC) were counted and the diameter of central vein and the area of micro-vessel in femur were measured. The effect of Ligustrazine on hematopoietic stem cells was observed by colony forming unit of spleen (CFU-S). The effect of Ligustrazine on hemopoietic progenitors was studied by observing the number of progenitors of Granulocytes/Macrophage on day 10 and day 20 after BMT. In Ligustrazine-treated group, the diameter of center veins and the area of micro-vessel of femur were all significantly less than the control group 7, 10, 15, 21 days after BMT (P<0.01). In addition, Ligustrazine significantly increased the number of CFU-S on day 10 and the number of CFU-GM on day 10, 20 after BMT. These results indicate that Ligustrazine can accelerate the histogenesis of hemopoietic bone marrow, which may be one mechanism by which Ligustrazine promotes hematopoietic reconstitution after BMT.
The effect of nitric oxide donor sodium nitroprusside (SNP) on resting membrane potential (Em) and potassium currents of the bronchial smooth muscle cells from rats was investigated. All experiments were conducted in conventional whole-cell configuration. The changes of Em and potassium currents after addition of 0.1 mmol/L SNP were measured under the current-clamp mode and the voltage-clamp mode respectively. Results showed that (1) SNP could decrease the Em from −33.8±7.4 mV to −43.7±6.7 mV (n=10,P<0.01); (2) SNP could increase the Ca2+-activated K+ channel peak currents under ramp protocol from 466.9±180. 1 pA to 597.7±237.6 pA (n=7,P<0.01), and the currents under pulse protocol at +50 mV were increased from 544.2±145.4 pA to 678.1±206.2 pA (n=6,P<0.05); (3) SNP also could increase voltage-gated K+ channel peak currents under ramp protocol from 389.6±84.1 pA to 526.7±98.7 pA (n=7,P<0.01), the currents under pulse protocol at +50 mV were increased from 275.7±85.2 pA to 444.3±128.5 pA (n=6,P<0.01). It was concluded that SNP increases the activities of Ca2+-activated K+ channels and voltage-gated K+ channels and leads to K+ efflux and hyperpolarization of the cell membrane, resulting in a decrease of the cell excitement.
To elucidate role of the three enzymes in hepatocarcinogenesis, hMTH1, hOGG1 and hMYH, mRNA expression were examined by using RT/semi-quantitative real-time PCR and 8-O-HdG levels was studied by HPLC/ECD in HCC and non-tumorous liver tissue of 21 patients with hepatocellular carcinoma (HCC). It was found that the 8-OHdG level in non-tumourous liver tissue was significantly higher than in HCC tissue (P=0.006), and this was correlated with the degree of inflammation. The hMTH1 expression in HCC tissue was significantly higher than in nontumorous liver tissue (P=0.014). Inversely, The hMYHα expression was significantly increased (P=0.039) in non-tumorous liver tissue. No difference was seen in hOGG1 expression in non-tumorous liver and HCC tissue. A significant linear correlation between hMTH1 and hOGG1 expression was found both in HCC tissue (r=0.809,P<0.001) and in non-tumorous liver tissue (r=0. 883,P<0.001). Our findings suggested a reactive rather than pathogenic role of the DNA repair enzymes in the hepatocarcinogenesis.
The effect of ginsenoside Rb1 on cardiomyocyte apotosis after ischemia (30 min) and reperfusion (6 h) in rats was observed. The ischemia/reperfusion heart model was established by ligating left anterior descending branch of coronary artery in Wistar rats. The apoptotic cardiomyocytes were examined under transmission electron microscopy and counted byin situ nick end labeling (TUNEL) method and light microscopy. Results showed that (1) The apoptotic cardiomyocytes were found in ischemic regions in the ischemia/reperfusion group, but not in the sham-operating group under transmission electron microscopy; (2) The number of apoptotic cells were 134.45±45.61/field in the ischemia/reperfusion group, 0/field in the sham-operating group and 51.65±13.71/field in the ginsenoside Rb1-treated group. The differences were significant among the three groups (P<0.01). It was concluded that myocardial ischemia-reperfusion could induce cardiomyocyte apoptosis, and ginsenoside Rb1 could significantly inhibit cardiomyocyte apoptosis induced by ischemia-reperfusion in rats, indicating that ginsenoside Rb1 could inhibit cardiomyocyte apoptosis induced by ischemia-reperfusion, thus alleviating ischemia-reperfusion injury.
The relationship between the hepatic ischemia/reperfusion (I/R) injury and the balance of nitric oxide/endothelins (NO/ET) was studied. The changes of the ratio of NO/ET and the hepatic injury were observed in a rat hepatic I/R model pretreated with several tool drugs. In the acute phase of hepatic I/R injury, the ratio of plasma NO/ET was reduced from 1.58±0.20 to 0.29±0.05 (P<0.01) and the hepatic damage deteriorated. NO donor L-Arg and ET receptor antagonist TAK-044 could alleviate the hepatic I/R injury to some degree, whereas NO synthase inhibitor L-NAME aggravated the damage. It was concluded that the hepatic I/R injury might be related with the disturbance of the NO/ET balance. Regulation of this balance might have an effect on the I/R injury.
The role of bcl-2 in the pathogenesis of colorectal tumor were studied. The expression of bcl-2 in the colorectal carcinoma and incisional edge tissue of tumor was detected by using SABC method. The results showed that the positive rate of bcl-2 was 69.6% in colorectal carcinoma and 47.6% in the incisional edge tissue respectively, with the difference being very significant (P=0.001). Bcl-2 positive rate was associated with Dukes' stage, but had nothing to do with histological classification. It was concluded that bcl-2 might play a significant role in the development of colorectal carcinoma.
In order to study the modulatory effects of compound polysaccharide Erweikang on the immune function of the immunosuppressive mice, the positive immune modulation of Erweikang at different doses and different time points was compared when normal saline and cyclophosphamide served as controls. The results showed that different doses of Erweikang could effectively reverse the decreased induction levels of NK, IL-2, γ-IFN and the contents of TNF and IgG of the immunosuppressive mice after administration of Erweikang for 7 to 14 days. It was suggested that compound polysaccharide Erweikang presents positive immune modulation in dose- and time-dependent manners.
To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1∶7) dispersible tablets, a randomized cross—over study was conducted in 18 healthy volunteers. A single oral dose of 1000 mg Clavulanate Potassium and Amoxicillin (1∶7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high-performance liquid chromatography. The main paramaters of T were: for Clavulanate Potassium and Amoxicillin, Cmax: 2.46±1.11 μg/ml and 18.81±7.26 μg/ml, Tmax: 1.12±0.23h and 1.30±0.34h, ACU(0–6h): 5.18±2.24 μg·h/ml and 45.09±14.53 μg·h/ml, t1/2: 1.43±0.44 h and 1.09±0.22 h., respectively. The relative bioavailability of T to R were 96.5±19.2% and 98.4±26.1%, respectively. Statistical analysis showed that the two formulations were bioequivalent.
The clinical effects of acupuncture on idiopathic male infertility in sperm parameter and on therapeutic results in assisted reproductive technology were investigated. 22 patients failed in intracytoplasmic sperm injection (ICSI) with idiopathic male infertility were treated with acupuncture twice weekly for 8 weeks, followed by ICSI treatment again. The sperm concentration, motility, morphology, fertilization rates and embryo quality were observed. Quick sperm motility after acupuncture (18.3%±9.6%) was significantly improved as compared with that before treatment (11.0%±7.5%,P<0.01). The normal sperm ratio was increased after acupuncture (21.1%±10.4% vs 16.2%±8.2%,P<0.05). The fertilization rates after acupuncture (66.2%) were obviously higher than that before treatment (40.2%,P<0.01). There was no significant difference in sperm concentration and general sperm motility between before and after acupuncture. The embryo quality after acupuncture was improved, but the difference between them was not significant (P>0.05). Acupuncture can improve sperm quality and fertilization rates in assisted reproductive technology.
To probe the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM) 77 patients with DCM, HLA-DRB1 gene polymorphism were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique and autoantibody against myocardial mitochondria ADP/ATP carrier were examined by using the Immunoblot analysis. The frequency of HLA-DRB1*0901 allele was significantly higher in DCM patients in which autoantibody against ADP/ATP carrier of myocardial mitochondria is positive in contrast with those in which the autoantibody is negative (25.46% vs 3.45%,P<0.05), the relative risk (RR) being 9.56. The other frequencies of HLA-DRB1 alleles have no significant difference in the antibody positive group and negative group. It is possible that a subset of DCM patients may exist in which autoimmunity is associated with genetic factors.
To evaluate the effects of left ventricular contractility on the changes of average image intensity (AII) of the myocardial integrated backscatter (IB) and cyclic variation in IB (CVIB), 7 adult mongrel dogs were studied. The magnitude of AII and CVIB were measured from myocardial IB carves before and after dobutamine or propranolol infusion. Dobutamine or propranolol did not affect the magnitude of AII (13.8±0.7 vs 14.7±0.5,P>0.05 or 14.3±0.5 vs 14.2±0.4,P>0.05). However, dobutamine produced a significant increase in the magnitude of CVIB (6.8±0.3 vs 9.5±0.6,P<0.001) and propranolol induced significant decrease in the magnitude of CVIB (7.1±0.2 vs 5.2±0.3,P<0.001). The changes of the magnitude of AII and CVIB in the myocardium have been demonstrated to reflect different myocardial physiological and pathological changes respectively. The alteration of contractility did not affect the magnitude of AII but induced significant change in CVIB. The increase of left ventricular contractility resulted in a significant rise of the magnitude of CVIB and the decrease of left ventricular contractility resulted in a significant fall of the magnitude of CVIB.
To determine the relationship between Barrett's esophagus (BE) and features of gastroesophageal acid reflux, 24 h esophageal pH monitoring was performed in 90 patients. The patients were divided into 3 groups: 31 subjects with BE, 21 with mild esophagitis and 38 with severe esophagitis. The following parameters were evaluated: the percentage time of pH<4; the number of reflux episodes over 5 min; the duration of longest episodes and DeMeester score over total period and the auterior three parameters in erect and supine position. All these parameters in BE were significantly different from those with mild esophagitis (P<0.01) and not significantly different from those with severe esophagitis (P>0.05). During supine position all the above parameters in BE were significantly different from those with reflux esophagitis (P<0.05). It is concluded that the quantity of acid reflux is not an important factor in development of BE in gastroesophageal reflux (GER), and the acid reflux in supine position might be important in development of BE in GER.
To study the manifestations of endoscopic retrograde cholangiopancreatography (ERCP) in patients of obstructive jaundice associated with HCC, 32 cases of histopathologically diagnosed HCC with obstructive jaundice were successfully examined with routine ERCP. 31 patients were demonstrated by ERCP as having malignant obstructive jaundice. Among them, 19 were hepatic perihilar bile duct stricture, 7 bile ductile tumorous thrombus, 3 perihilar bile duct stricture complicated with thrombus, 2 metastasis to hilar lymph node, and 1 common bile duct stone as proven by sphincterotomy. The malignant perihilar stricture was all of type III and IV by Bismuth standard of Klastin tumor. In patients identified as having bile duct tumor thrombus, by the Ueda classification, none was of type I and II; 1 type III a; 4 III b; 2 type IV. HCC with obstructive jaundice was mainly caused by the malignant infiltration of tumor, and most stricture was of serious nature. When major extra-hepatic bile duct was involved by tumor thrombus, obstructive jaundice might develop. Malignant perihilar stricture and tumor thrombus might coexist in some patients. Jaundice was rarely caused by hepatic hilar lymph node metastasis. Jaundice was not necessarily caused by tumors and sometimes, it might be caused by common bile stones. Care should be exercised in differentiation diagnosis in such patients.
To elevate the clinical value of3D-FLASH in the diagnosis of anal fistula and compare it with convationd MR sequence, MR sequences, consisting of spin echo T1WI, turbo invertion recovery magnitude (TIRM), fast low-angle shot image (FLASH), mon-enhancement and enhancement substraction and coronary reconstructing, was conducted in15 cases suspected of anal fistula. Comparison was made among the three sequences in display rate of internal fistula, external fistula, the branch of fistule connulas. Our results showed that1 patient had perianal abscess.24 different anal fistulas were identified in14 patients, and10 of them was complicated with perianal abscess and8 of them with complex multi-branch fistula. The display rate of3D-FLASH sequence was much higher than those of T1WI and TIRM in all cases. It is concluded that3D-FLASH squence is an senstive and time-efficient technique for the dignosis of anal fistula.
The reliability and reliable indexes of quantitative assessment of coronary flow reserve (CFR) by using time-intensity curve (TIC) via myocardial contrast echocardiography were investigated. The TIC variables were obtained by employing acoustic densitometry (AD) technique before and after acetylcholine (Ach) injection in 12 dogs. Meanwhile, the correlation between these variables and CFR was analyzed. Among the variables derived from TIC, peak intensity (PI), area under the curve (AUC) and descending slope (DS) were increased significantly (P<0.05) with the increase of coronary blood flow after Ach injection. Conversely, time-to-peak (TP), half-time of descent (HT), and mean-transit-time (MTT) were decreased remarkably (P<0.0001). The PI and AUC ratios from post-to pre-Ach injection were strongly associated with CFR with the correlation coefficient (r) being 0.8366 and 0.8824, respectively. It is reliable by using the variables derived from TIC with myocardial contrast echocardiography to quantitatively evaluate regional myocardial CFR. The PI and AUC ratios from post-to pre-Ach injection are the reliable indexes for quantitative assessment of CFR.
To explore the relationship between β-amyloid (Aβ) and the pathogenesis of Alzheimer disease (AD), after injection of β-amyloid into the rat brain, the apoptosis of nerve cells and acetylcholine (Ach) content in rat hippocampus were examined by employing TUNEL technique and base hydroxylamine colorimetry respectively. The influence of age and glucocorticoid on the neurotoxic effect of Aβ was also analyzed. Aβ peptide could strongly induce the apoptosis of neurons in hippocampus, cortex and striate body (P<0.05 orP<0.01). In addition, the senility and glucocorticoid pre-treatment could enhance the toxic effect of Aβ(P<0.05 orP<0.01). It is concluded that Aβ may play an important role in the pathogenesis of Alzheimer disease via its induction of apoptosis of neurons and by decreasing the content of the Ach.
In this study antigen-independent factor in the pathogenesis of chronic rejection of organ transplants was examined. Kidney isografts and allografts were transplanted orthotopically into bilaterally nephroectomized rat recipients and studied functionally, morphologically and immunohistologically, at serial intervals up to 52 weeks after transplantation. Allograft recipients developed progressive proteinuria after 12 weeks, with gradual renal failure ultimately leading to death. At the same time, morphological changes, including progressive arteriosclerosis and glomerulosclerosis, tubular atrophy and interstitial fibrosis, developed. Immunohistologically, macrophages infiltrated glomeruli during this period and cytokines became unregulated. Our results showed that antigen-independent functional and morphological changes occurred in long-term kidney isografts and mimicked those appearing much earlier in allografts that reject chronically. Initial injury and extent of functioning renal mass is suggested to be important factor for such late changes.
To explore whether the imprinting status of IGF-2 in the malignant epithelial ovarian tumors is different from that in benign tumors, the target sequences (DNA and RNA) which contain a polymorphism site for ApaI restriction endonuclease digestion were amplified with PCR and RT-PCR methods. Then the PCR/RT-PCR products were digested by ApaI. The IGF-2 transcriptional pattern came out from the results of endonucleases digestion. Among the 36 cases of benign epithelial ovarian tumors, 20 were heterozygous for ApaI locus and all showed genomic imprinting. While in the malignant group, 22 were heterozygous for ApaI locus but six were found to lose imprinting. Significant differences existed between the two groups (P<0.05). Loss of imprinting of IGF-2 may serve as a marker for differentiating the malignant ovarian cancers from the benign ones. In a new field of molecular genetics, our research provides an experimental basis for genetic diagnosis and treatment of the ovarian cancers.
One hundred and sixteen senile patients (older than 65 years) with chronic heart failure (CHF) were analyzed retrospectively in order to verify if old patients with CHF would benefit from long-term (one year) angiotension-converting enzyme inhibitor (ACEI) treatment. The frequency of drugs (including ACEI, digitalis and diuretic) used was stratified into four degrees accordingly. Development of the CHF was scored with regard to relapse rate and severity of this disease. Stepwise regression analysis was applied to explore the relationship between the scored outcome of CHF and the frequency of individual drug administration. A significant relationship of the scored outcome of CHF to the frequency of ACEI usage but not to digitalis nor to diuretics was found (partial coefficient of the correlationr=0.42,P=0.002). It was concluded that the longterm administration of ACEI improves the outcome of CHF in senile patients.
In order to investigate the human cytomegalovirus (HCMV) infection, the mouse cytomegalovirus (MCMV) infected mice were experimentally studied. 6 to 8 week old female BALB/C mice with immunosuppression were selected to undergo the MCMV inoculations: intracranial inoculation and peritoneal inoculation. MCMV of the infected mice in various organs and tissues were detected by using β-gal staining andin situ nucleic acid hybridization assay. The pathological changes were observed in HE staining paraffin-embedded sections. It was found that all the MCMV infected mice showed the retardation of growth and development, and feather looseness. Both intracranial inoculation of 104 PFU viruses or peritoneal inoculation of 106 PFU viruses resulted in the pathological changes, to some extent, of various organs and tissues in the mice. The pathological changes in liver were consistent with the amount of β-gal staining positive cells, indicating the liver lesions were mainly caused by viral proliferation. It was also found that the viruses in the immunosuppressed mice subjected to intracranial inoculation could spread to whole body organs, while the viruses in the immunosuppressed mice subjected to intrapeitoneal inoculation couldn't spread to the brain, suggesting blood-brain barrier could prevent the virus from spreading to the brain.