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Biomedical subjects

S Zhong

Publications and source records attributed to S Zhong.

At least 73 records · Page 4Linked to original sources
PubMed2000

Hepatitis B virus reactivation in patients undergoing cytotoxic chemotherapy for solid tumours: precore/core mutations may play an important role.

Reactivation of the hepatitis B virus (HBV) is a rare, but well described complication of cytotoxic chemotherapy that may result in hepatic failure. Patients who are chronic carriers of the HBV and who have a G to A mutation at nucleotide 1896 in the precore region may develop more severe liver disease, possibly because of rapid selection and enhanced replication ability of the mutant strain. Such mutant viruses have been implicated occasionally in chemotherapy induced reactivation of hepatitis B virus. In this report, 5 patients with solid tumours were identified to have developed severe hepatitis B virus related liver disease during treatment with cytotoxic agents (with dexamethasone as anti-emetic). All had clinical and serological evidence of reactivation of the HBV. Three patients developed icteric hepatitis; 2 fully recovered, and 1 had died from progressive metastatic disease while recovering from the reactivation. The other two died from progressive liver failure. Direct sequencing of the polymerase chain reaction (PCR) products of the precore (preC) and precore promoter region of the HBV-DNA was carried out on the patients' serum samples taken during the episode of reactivation. In each case, similar mutations (G to A) in nucleotide 1896 of the preC region were found, together with additional mutations in the preC promoter. The present findings suggest that reactivation involving a mutant hepatitis B virus may lead to liver failure, which is possibly more severe than that caused by wild type HBV, and can be triggered by cytotoxic chemotherapy, or the administration of corticosteroids. In Eastern Asia the HBV carriage rate in adults is high. HBV reactivation and severe liver disease during cytotoxic treatment may become a serious and common problem in this region as cytotoxic chemotherapy is more widely used. Patients should be screened routinely for HBsAg in endemic areas of chronic hepatitis B virus infection prior to receiving cytotoxic treatment. The possibility of HBV reactivation should be considered in patients developing liver dysfunction. Patients who are HBeAg negative/Anti-HBe positive, and are suspected to be having an HBV reactivation, should have HBV-DNA levels measured for confirmation as they may carry a mutant HBV.

Adult↗
PubMed2000

Anti-HBV effect of targeted antisense RNA against HBV C gene.

OBJECTIVE: To investigate the anti-HBV effect of targeted antisense RNA to hepatic cells. METHODS: pREP4-aC which would transcript antisense RNA against HBV C gene in eukaryotic cells were delivered into 2.2.15 cells by glactosylated poly-L-lisine (Gal-PLL), and the positive cells were selected. HBsAg, HBeAg and HBV DNA produced by 2. 2.15 cells were detected with ELISA or Southern blot during the experiment, and the cytotoxicity of targeted antisense on 2.2.15 cells was observed. RESULTS: The inhibition effect on HBsAg, HBeAg and HBV DNA occurred at the 24th hour after delivery and reached the highest level at the 6th day, and kept at lest two months. No cytotoxicity on 2.2.15 cells was observed. CONCLUSION: The targeted antisense against HBV C gene by delivery of Gal-PLL could effectively inhibit the antigen expression of HBV and DNA replication.

Antiviral Agents↗
PubMed2000

[Effect of domestic glutathione on the alcoholic liver disease].

OBJECTIVE: To evaluate the effect and safety of domestic glutathione (GSH) on serum ALT, AST, SB levels in alcoholic liver disease (ALD) by multicenter, randomized and TAD controlled trial. METHODS: All the 110 patients with ALD enrolled had a history of drinking over 80g-120g daily for 5 years, and were randomized either into GSH (continuous infusion of 600g daily for 30d) or TAD (with the same dosage, course and route as GSH) group. The efficacy and safery were evaluated with clinical and biochemical (ALT, AST and GGT) parameters. RESULTS: After 8 weeks of treatment, the clinical signs were improved at a different degree in both groups. ALT, AST and SB showed no significant difference in the two groups (the efficacy rate of 93% vs 96%, P>0.05). CONCLUSION: The domestic GSH, with a good tolerance and safety, has a sound efficacy in the improvement of clinical signs and hepatic functions.

Adolescent↗
PubMed2000

[Applied anatomy of the transverse rectus abdominis musculocutaneous (TRAM) flap in relation to the eleventh or twelfth thoracic nerve].

OBJECTIVE: To observe the distribution of the terminal branches of the eleventh and twelfth thoracic nerve(T11, T12) for the anatomical basis and operation key points of the transverse rectus abdominis musculocutaneous(TRAM) flap with T11, T12. METHODS: The anterior abdominal wall was investigated through anatomical dissection in 22 embalmed cadavers. RESULTS: Cutaneous nerve distribution in the TRAM flap came mainly from T11, T12. They run obliquely between transverse abdominis and obliquus internus abdominis muscle. At the lateral edge of the rectus abdominis, they piece the anterior rectus sheath into the muscle. While supplying the muscle they pass on to supply the anterior rectus sheath and the overlying skin. CONCLUSION: It is possible to preserve T11, T12 in the TRAM flap, which would favour rapid return of flap sensation.

Female↗
PubMed2000

Pancreatic insulinomas: experience in 220 patients.

OBJECTIVE: To summarize the experience in the diagnosis and treatment of insulinoma. METHODS: We retrospectively reviewed 220 patients with insulinoma confirmed surgically in the PUMC Hospital from 1953 to 1999. They were 131 men and 89 women, aged on average 39 years. RESULTS: In the 220 patients, the average interval from the onset of symptoms to diagnosis was 35 months. 54% of the patients were misdiagnosed before admission to the hospital. In 214 patients underwent operation, 201 (93.9%) had benign tumor and 12 (5.6%) malignant one. The diameter of 78% tumors was less than 2cm. 90.7% tumors were single and 9.3% were multiple. 37.1% tumors were located in the head and uncinate process of the pancreas, 26.1% in the body, 36.1% in the tail, and 0.7% ectopic. 95.5% patients had Whipple's triad and the ratio of insulin to glucose was greater than 0.3 in 89% patients. The positive rates of B-ultrasound, CT and MRI for localization before operation were low, but those of angiography and PTPC were 62.8% and 88% respectively. Most patients could be cured by simple enucleation of tumor. The main complications were pancreatic fistulae and pancreatitis. CONCLUSION: It is important for surgeons to familiarize with insulinoma, the most common islet cell tumor, for a better treatment.

Adult↗
PubMed2000

[Three-dimensional reconstruction of internal auditory meatus and anatomical study of the inner structures].

OBJECTIVE: To provide anatomical basis for surgical operation in internal auditory meatus (IAM). METHODS: Structures of cerebellopontine angle (CPA) and IAM in 25 temporal bone specimens (50 sides) fixed in formalin were measured. Three-dimensional reconstruction (3DR) of IAM in 13 normal adults (26 sides) was conducted using spiral CT scanning. RESULTS: IAM took a conic shape with larger inside and smaller outside. The average width of IAM was (4.16 +/- 1.23) mm(2.87-6.83 mm) in horizontal dimension, the average height was (3.14 +/- 1.01) mm(2.23-4.45 mm) in vertical dimension, the average length was (8.67 +/- 2.31) mm (6.77-11.22 mm), the average volume was (98.23 +/- 16.56) mm3(67.44-133.21 mm3). There were 1-4 internal auditory arteries branched from the anterior-inferior cerebellar artery, which formed a vascular ansa near the opening of IAM. The average length of the facial nerve in IAM was (0.98 +/- 0.03) mm (0.89-1.07 mm), the average diameter of vestibulocochlear nerve was (1.67 +/- 0.05) mm (1.42-1.97 mm), the average diameter of the intermediate nerve (0.23 +/- 0.02) mm (0.19-0.26 mm). CONCLUSION: It is necessary to pay attention to types of vascular ansa and relative nerve location in IAM during operation.

Adult↗
PubMed1999

A role for PML and the nuclear body in genomic stability.

The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumor suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells. The Bloom syndrome gene BLM encodes a RecQ DNA helicase, whose absence from the cell results in genomic instability epitomized by high levels of sister-chromatid exchange (SCE) and cancer predisposition. We show here that BLM co-localizes with PML to the NB. In cells from persons with Bloom syndrome the localization of PML is unperturbed, whereas in APL cells carrying the PML-RARalpha oncoprotein, both PML and BLM are delocalized from the NB into microspeckled nuclear regions. Treatment with retinoic acid (RA) induces the relocalization of both proteins to the NB. In primary PML-/- cells, BLM fails to accumulate in the NB. Strikingly, in PML-/- cells the frequency of SCEs is increased relative to PML+/+ cells. These data demonstrate that BLM is a constituent of the NB and that PML is required for its accumulation in these nuclear domains and for the normal function of BLM. Thus, our findings suggest a role for BLM in APL pathogenesis and implicate the PML NB in the maintenance of genomic stability.

Adenosine Triphosphatases↗
PubMed1999

Detection of apolipoprotein B mRNA editing by peptide nucleic acid mediated PCR clamping.

Apolipoprotein B (apoB) mRNA editing leads to a single base change in its mRNA and the production of apoB-48. Currently, the degree of apoB mRNA editing is analyzed by the RT-PCR primer extension method. While this method is quantitative, it is labor intensive, utilizes radioactivity for labeling and may not be sensitive enough to discriminate between low levels of editing and inherent assay background levels. Peptide nucleic acid (PNA) oligonucletides have been used in single point mutation detection through PCR clamping. In the present work, we developed a PCR based assay which can detect the single base change responsible for the apoB-48 production. We found that as low as 0.5% of the edited form can be clearly detected by PNA mediated PCR clamping. When combined with the primer extension assay, an approximately 180-fold enrichment of the edited percentage is observed, reflecting selected PCR amplification of templates containing the edited base.

Apolipoprotein B-48↗
PubMed1999

Lymphohematopoietic stem cell engraftment.

Traditional dogma has stated that space needs to be opened by cytoxic myeloablative therapy in order for marrow stem cells to engraft. Recent work in murine transplant models, however, indicates that engraftment is determined by the ratio of donor to host stem cells, i.e., stem cell competition. One hundred centigray whole body irradiation is stem cell toxic and nonmyelotoxic, thus allowing for higher donor chimerism in a murine syngeneic transplant setting. This nontoxic stem cell transplantation can be applied to allogeneic transplant with the addition of a tolerizing step; in this case presensitization with donor spleen cells and administration of CD40 ligand antibody to block costimulation. The stem cells that engraft in the nonmyeloablated are in G0, but are rapidly induced (by 12 hours) to enter the S phase after in vivo engraftment. Exposure of murine marrow to cytokines (IL-3, IL-6, IL-11 and steel factor) expands progenitor clones, induces stem cells into cell cycle, and causes a fluctuating engraftment phenotype tied to phase of cell cycle. These data indicate that the concepts of stem cell competition and fluctuation of stem cell phenotype with cell cycle transit should underlie any new stem cell engraftment strategy.

Animals↗
PubMed1999

Traumatic instabilities of the cervical spine caused by high-speed axial compression in a human model. An in vitro biomechanical study.

STUDY DESIGN: Traumatic injury of the cervical spine was produced on human cadavers and evaluated with instability tests and radiographs. OBJECTIVE: To relate traumatic injuries of the cervical spine to instability and patterns of traumatic injury to different levels of impact energy. SUMMARY OF BACKGROUND DATA: Data from young human cadavers are rare in traumatic models of the cervical spine, and instabilities caused by axial compression with different impacts remain unknown. METHODS: Fourteen cervical spine specimens (C2-C4) obtained from fresh human cadavers were divided evenly into two groups and subjected to axial compressive impact with 30 J and 50 J impact energy, respectively. Pure moments in flexion-extension, left/right lateral bending, and left/right axial rotation were applied to each specimen before and after trauma. The maximum moment was 2.0 Nm in each case. Ranges of motion and neutral zones were measured using stereophotogrammetry. RESULTS: Ranges of motion and neutral zones for both groups increased after trauma. No bony injury was observed on the radiographs after trauma with 30 J, but motions increased significantly in flexion, extension, and axial rotation. All specimens showed bony injuries after trauma with 50 J, whereas motions continued to increase significantly in all directions. The relative neutral zone values were larger than the corresponding range of motion values, except in flexion-extension after trauma with 50 J. CONCLUSIONS: The injury patterns of the cervical spine were associated with impact energy, and a high level of impact energy could produce either three-column injury or anterior middle-column injury. Instabilities of the cervical spine caused by compressive trauma increased with the level of impact energy. The neutral zone was more sensitive than the range of motion in representing spinal instability, whereas instability testing was more sensitive than radiographs in evaluating traumatic injury of cervical spine.

Adult↗
PubMed1999

Human brain alpha rhythm: nonlinear oscillation or filtered noise?

The mechanism for generation of the alpha rhythm is controversial. In the current study, analysis in the time and frequency domains revealed that the alpha rhythm recorded from the scalp overlying the human occipital cortex can be entrained to the second or third harmonic of low frequency light flashes. These results support the view that the alpha rhythm is generated by a nonlinear oscillator rather than a narrow-band transmission system acting as a filter.

Adult↗
PubMed1999

RB regulates the stability and the apoptotic function of p53 via MDM2.

The binding of RB to MDM2 is shown to be essential for RB to overcome both the antiapoptotic function of MDM2 and the MDM2-dependent degradation of p53. The RB-MDM2 interaction does not prevent MDM2 from inhibiting p53-dependent transcription, but the RB-MDM2 complex still binds to p53. Since RB specifically rescues the apoptotic function but not the transcriptional activity of p53 from negative regulation by MDM2, transactivation by wild-type p53 is not required for the apoptotic function of p53. However, an RB-MDM2-p53 trimeric complex is active in p53-mediated transrepression. These data link directly the function of two tumor suppressor proteins and demonstrate a novel role of RB in regulating the apoptotic function of p53.

Apoptosis↗
PubMed1999

The biological response of MCF7 breast cancer cells to proteosome inhibition or gamma-radiation is unrelated to the level of p53 induction.

The p53 tumour suppressor is stabilised following exposure to genotoxic agents, such as gamma-radiation. Cell responses to p53 stabilisation include induction of apoptosis and/or cell cycle arrest. Several studies have suggested that gamma-radiation stabilises p53 by blocking ubiquitin mediated proteolysis. Here we have compared the biological activities of p53 stabilized following exposure to gamma-radiation or treatment with the proteosome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) in MCF7 cells with wild type p53. Stabilisation of p53 by ALLN was reversible and was not blocked by caffeine. Although ALLN was a more effective p53 stabilising agent than gamma-radiation, ALLN was not as effective at inducing cell cycle arrest/apoptosis as gamma-radiation. Although p53 stabilised by ALLN and gamma-radiation were both able to bind DNA and activate transcription, ALLN did not increase expression of BAX, which is involved in p53-induced apoptosis. Therefore, p53 stabilised by different agents is not always biologically active to the same extent and additional alterations triggered by gamma-radiation may enable p53 to activate a subset of critical target genes, such as BAX, which are required for p53 responses.

Journal Article↗
PubMed1999

A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins.

PML and Tif1a are fused to RARA and Braf, respectively, resulting in the production of PML-RARalpha and Tif1alpha-B-Raf (T18) oncoproteins. Here we show that PML, Tif1alpha and RXRalpha/RARalpha function together in a transcription complex that is dependent on retinoic acid (RA). We found that PML acts as a ligand-dependent coactivator of RXRalpha/RARalpha. PML interacts with Tif1alpha and CBP. In Pml-/- cells, the RA-dependent induction of genes such as RARB2 and the ability of Tif1alpha and CBP to act as transcriptional coactivators on RA are impaired. We show that both PML and Tif1alpha are growth suppressors required for the growth-inhibitory activity of RA. T18, similar to PML-RARalpha, disrupts the RA-dependent activity of this complex in a dominant-negative manner resulting in a growth advantage. Our data define a new pathway for the control of cell growth and tumorigenesis, and provide a new model for the pathogenesis of acute promyelocytic leukaemia (APL).

Animals↗
PubMed1999

Hepatitis B envelope protein mutants in human hepatocellular carcinoma tissues.

Hepatitis B virus (HBV) envelope mutants in the region encoding the highly immunogenic major hydrophilic region (MHR) of surface antigen (HBsAg) have been associated with vaccine failure and chronic infection. To determine if these mutants are associated with the development of human hepatocellular carcinoma (HCC), we measured the frequency and nature of such mutants in 23 HBV-associated HCC and various control tissues by performing Southern blot analysis, the polymerase chain reaction (PCR) and direct sequencing. The HBV genome was present mainly in an integrated form and, in most of the samples, the envelope gene was intact. Amino acid substitutions, involving the MHR region in the HCC tissues, were analysed in 11 (61. 1%) of 18 patients with HCC. The mutation Gly145Arg, which has been reported to be associated with immunoevasion, was found in seven of the 18 HCC tissues. A significantly higher frequency of mutations was found in HCC tissues (11 of 18) than in the corresponding non-tumorous tissue of the same patients (one of eight), and in samples from patients with acute (one of 19) or chronic (three of 31) HBV infection (P < 0.001, Fisher's exact test). The accumulation of these envelope mutants in the HCC tissue suggests that such envelope protein mutations may play a role in the process of oncogenesis and that specific vaccines may need to be developed to prevent the occurrence of mutant HBV-associated HCC. Alternatively, the progressive accumulation of mutants in patients with acute hepatitis, chronic hepatitis and HCC may reflect the increased length of duration of HBV infection in these groups of liver lesions.

Adult↗
PubMed1999

Differential patterns of spinal sympathetic outflow involving a 10-Hz rhythm.

Time and frequency domain analyses were used to examine the changes in the relationships between the discharges of the inferior cardiac (CN) and vertebral (VN) postganglionic sympathetic nerves produced by electrical activation of the midbrain periaqueductal gray (PAG) in urethan-anesthetized, baroreceptor-denervated cats. CN-VN coherence and phase angle in the 10-Hz band served as measures of the coupling of the central oscillators controlling these nerves. The 10-Hz rhythm in CN and VN discharges was entrained 1:1 to electrical stimuli applied to the PAG at frequencies between 7 and 12 Hz. CN 10-Hz discharges were increased, and VN 10-Hz discharges were decreased when the frequency of PAG stimulation was equal to or above that of the free-running rhythm. In contrast, stimulation of the same PAG sites at lower frequencies increased, albeit disproportionately, the 10-Hz discharges of both nerves. In either case, PAG stimulation significantly increased the phase angle between the two signals (VN 10-Hz activity lagged CN activity); coherence values relating their discharges were little affected. However, the increase in phase angle was significantly more pronounced when the 10-Hz discharges of the two nerves were reciprocally affected. Importantly, partialization of the phase spectrum using the PAG stimuli did not reverse the change in CN-VN phase angle. This observation suggests that the increase in the CN-VN phase angle reflected changes in the phase relations between coupled oscillators in the brain stem rather than the difference in conduction times to the two nerves from the site of PAG stimulation. In contrast to the effects elicited by PAG stimulation, stimulation of the medullary lateral tegmental field induced uniform increases in the 10-Hz discharges of the two nerves and no change in the CN-VN phase angle. Our results demonstrate that changes in the phase relations among coupled brain stem 10-Hz oscillators are accompanied by differential patterns of spinal sympathetic outflow. The reciprocal changes in CN and VN discharges produced by PAG stimulation are consistent with the pattern of spinal sympathetic outflow expected during the defense reaction.

Animals↗
PubMed1999

ApoA-II maintains HDL levels in part by inhibition of hepatic lipase. Studies In apoA-II and hepatic lipase double knockout mice.

High density lipoprotein (HDL) cholesterol levels are inversely related to the risk of developing coronary heart disease. Apolipoprotein (apo) A-II is the second most abundant HDL apolipoprotein and apoA-II knockout mice show a 70% reduction in HDL cholesterol levels. There is also evidence, using human apoA-II transgenic mice, that apoA-II can prevent hepatic lipase-mediated HDL triglyceride hydrolysis and reduction in HDL size. These observations suggest the hypothesis that apoA-II maintains HDL levels, at least in part, by inhibiting hepatic lipase. To evaluate this, apoA-II knockout mice were crossbred with hepatic lipase knockout mice. Compared to apoA-II-deficient mice, in double knockout mice there were increased HDL cholesterol levels (57% in males and 60% in females), increased HDL size, and decreased HDL cholesteryl ester fractional catabolic rate. In vitro incubation studies of plasma from apoA-II knockout mice, which contains largely apoA-I HDL particles, showed active lipolysis of HDL triglyceride, whereas similar studies of plasma from apoA-I knockout mice, which contains largely apoA-II particles, did not. In summary, these results strongly suggest that apoA-II is a physiological inhibitor of hepatic lipase and that this is at least part of the mechanism whereby apoA-II maintains HDL cholesterol levels.

Animals↗