Biomedical subjects

S Zhong

Publications and source records attributed to S Zhong.

At least 127 records · Page 7Linked to original sources

PubMed1995

Physical and functional interactions between p53 and cell cycle co-operating transcription factors, E2F1 and DP1.

One way in which wild-type p53 is able to regulate cell cycle progression is thought to be via the induction of its downstream target gene Waf1/CIP1, thus indirectly regulating the transcriptional activity of E2F. The E2F transcription factors are known to be key effectors of the cell cycle. We report here that there is a physical and functional interaction between p53 and two of the components of the E2F transcription factors, E2F1 and DP1. The expression of wild-type p53 can inhibit the transcriptional activity of E2F, and the expression of both E2F1 and DP1 can also downregulate p53-dependent transcription. The transcriptional activity of p53 is known to be inhibited by the direct binding of mdm2, but we demonstrate here that both E2F1 and DP1 can inhibit p53 transcriptional activity independently of mdm2. Detailed studies of protein-protein interactions have provided evidence that E2F1 and its co-operating factor DP1 can complex with p53 both in vitro and in vivo.

Animals↗

PubMed1995

Biological and structural characterization of a Ras transforming mutation at the phenylalanine-156 residue, which is conserved in all members of the Ras superfamily.

Although Ras residue phenylalanine-156 (F156) is strictly conserved in all members of the Ras superfamily of proteins, it is located outside of the consensus GDP/GTP-binding pocket. Its location within the hydrophobic core of Ras suggests that its strict conservation reflects a crucial role in structural stability. However, mutation of the equivalent residue (F157L) in the Drosophila Ras-related protein Rap results in a gain-of-function phenotype, suggesting an alternative role for this residue. Therefore, we have introduced an F156L mutation into Ras to evaluate the role of this residue in Ras structure and function. Whereas introduction of this mutation activated the transforming potential of wild-type Ras, it did not impair that of oncogenic Ras. Further, Ras (156L) exhibited an extremely rapid off rate for bound GDP/GTP in vitro and showed increased levels of Ras.GTP in vivo. To determine the structural basis for these altered properties, we used high-resolution nuclear magnetic resonance spectroscopy. The F156L mutation caused loss of contact with residues 6, 23, 55, and 79, resulting in disruption of secondary structure in alpha-helix 1 and in beta-sheets 1-5. These major structural changes contrast with the isolated alterations induced by oncogenic mutation (residues 12 or 61) that perturb GTPase activity, and instead, weaken Ras contacts with Mg2+ and its guanine nucleotide substrate and result in increased rates of GDP/GTP dissociation. Altogether, these observations demonstrate the essential role of this conserved residue in Ras structure and its function as a regulated GDP/GTP switch.

3T3 Cells↗

PubMed1995

Differential relationships among 10-Hz rhythmic discharges of sympathetic nerves with different targets depend on supraspinal rather than spinal mechanisms.

In urethane-anesthetized cats, ordinary and partial coherence values relating the 10-Hz rhythmic discharges of sympathetic nerves located on opposite sides of the body were not significantly affected by midsagittal section of the spinal cord from the seventh cervical through eighth thoracic or first cervical through eighth cervical segments. Thus, coordination of the 10-Hz discharges of the nerves occurred at a supraspinal level.

Action Potentials↗

PubMed1995

Synchronization of cardiac-related discharges of sympathetic nerves with inputs from widely separated spinal segments.

We used phase spectral analysis to study the relationships between the cardiac-related discharges of pairs of postganglionic sympathetic nerves in urethan-anesthetized or decerebrate cats. Phase angle when converted to a time interval should equal the difference in conduction times from the brain to the nerves (i.e., transportation lag) if their cardiac-related discharges have a common central source. Transportation lag was estimated as the difference in the onset latencies of activation of the nerves by electrical stimulation of the medulla or cervical spinal cord. The phase angle for the cardiac-related discharges of two nerves was not always equivalent in time to the transportation lag. For example, in some cases the cardiac-related discharges of the renal nerve were coincident with or led those of the inferior cardiac nerve. In contrast, the electrically evoked responses of the renal nerve lagged those of the inferior cardiac nerve by > or = 32 ms. These observations are consistent with a model of multiple and dynamically coupled brain stem generators of the cardiac-related rhythm, each controlling a different sympathetic nerve or exerting nonuniform influences on different portions of the spinal sympathetic outflow.

Anesthesia, General↗

PubMed1995

[Effect of 153Sm-EDTMP on hematopoiesis and vital organs of 93 patients with bone tumor].

In the present study data on blood cell count, serum biochemistry, electrolyte, enzyme and vital organs of 93 patients with bone tumor or metastasis were investigated before and after treatment with 153Sm-EDTMP. The results showed that, 7 days and 30 days after the administration of 153Sm-EDTMP (< 29.6 MBq) (0.8 mCi/kg), the levels of hemoglobin, WBC lymphocyte count, and the liver and kidney function of all patients were not significantly different from the baseline data before treatment (P > 0.05). Although at 7 days, there was a declination of the granulocyte count, it returned to normal at 30 days (P > 0.05). The platelet count was significantly decreased (0.05 > P > 0.01). at 30 days after the administration of 153Sm-EDTMP. Thirteen patients received 74-185 MBq (2-5mCi/kg) and their myelo biopsies at 3 and 18 months showed no sign of acute or chronic toxicosis.

Adult↗

PubMed1995

[Inhibition of hepatitis B viral gene expression and replication in vitro by targeted antisense oligonucleotides].

We chose the 2.2. 15 cells as an in vitro cell culture assay system, and identified the surface antigen subtype of hepatitis B virus (HBV) DNA in the cells, by using the amplification of polymerase chain reaction and directed sequencing of amplified products. According to the result of the sequencing, a 16-mer phosphorothioate analogue of the antisense oligonucleotide (PS-ASON) directed against the HBV U5-unique region was synthesized and then linked with two liver-targeting ligands. The galactosylated human serum albumin coupled poly-L-lysine and the galactosylated poly-L-lysine. The effect of different modifications of ASONs on the expression of HBV gene was compared by using the 2.2. 15 cells. In the same experimental conditions, the inhibitary effects of surface antigen (HBsAg) and antigen (HBeAg) by PS-ASON were 70% and 58% respectively, and those of HBsAg and HBeAg by ligand-PS-ASONs were 90%-96% and 78%-82%. In the same time, the amount of HBV NDA in culture supernatant and cells was depressed significantly. Thus, the ligands targeted ASON to the hepatocytes were more effective inhibitors of HBV gene expression. ASONs were effective and specific inhibitors of HBV replication and expression, caused the dose-dependent inhibition of viral proteins and had no effect on cellular alpha-fetoprotein synthesis and no cytotoxicity.

Base Sequence↗

PubMed1995

[153Sm-EDTMP for moderate and severe bone cancer pain].

One hundred and thirty-six patients with bone cancer pain were treated with 153Sm-EDTMP (ethylenediamine-tetramethylene phosphonic acid). Pain free was noted in 49 cases (36%, 49/136) and pain relief in 77 cases (56.6%, 77/136), the total relief rate being 92.6% (126/136). The data from 76 patients with moderate and severe pain showed there were no significant relationships between the patients' age, the dose of 153Sm-EDTMP and the analgesic effects (P > 0.05). The pain relief observed in the patients with chest pain (ribs metastases) was earlier than that in other groups (P < 0.05). We didn't find any clinical side-effects, so 153Sm-EDTMP is safe for use.

Adult↗

PubMed1994

A modulatory role of central cholinergic transmission in control of the 10-Hz rhythm in sympathetic nerve discharge.

In 43 urethane-anesthetized or decerebrate, baroreceptor-denervated cats, spectral analysis showed that most of the power in sympathetic nerve discharge (SND) was at frequencies < 6 Hz. In 18 of these cats, physostigmine (100 micrograms/kg i.v.) induced a 10-Hz rhythm in inferior cardiac SND that was eliminated by atropine sulfate (0.25 mg/kg i.v.; n = 6). In contrast, the naturally occurring 10-Hz rhythm that appeared in SND in other experiments was atropine-insensitive (n = 6). The data indicate that central muscarinic cholinergic transmission is not essential for the naturally occurring 10-Hz rhythm. Nonetheless, facilitation of cholinergic transmission can induce a 10-Hz rhythm.

Animals↗

PubMed1994

Postnatal development in rat offspring delivered of dams with gestational hyperglycemia.

OBJECTIVES: Our purpose was to test the hypotheses that (1) offspring delivered of dams with gestational hyperglycemia will show metabolic abnormalities and (2) dams with repeated pregnancy but without lactation experience will demonstrate abnormal glucose metabolism long after the delivery of the third litter. STUDY DESIGN: Female rats went through three cycles of gestation-lactation, gestation-nonlactation, or no mating at all. The offspring were reared to 3 months of age, when half of each group were mated. Intravenous glucose tolerance testing was conducted at different times in dams and adult offspring. RESULTS: Nonlactation dams showed gestational hyperglycemia, insulin resistance, and hyperlipidemia during the third pregnancy. Impaired intravenous glucose tolerance testing was also apparent 1 week and 3 months after weaning in dams. Adult offspring nursed by nonlactation dams were glucose intolerant and had higher hepatic gluconeogenic enzyme activities and higher lipid levels in the pregnant state. CONCLUSION: Gestational hyperglycemia produced by repeated gestation without lactation could have a long-lasting effect on adult offspring.

Adipose Tissue↗

PubMed1994

Biomolecular applications of heteronuclear multidimensional NMR.

Recent advances in stable-isotope enrichment and heteronuclear multidimensional NMR techniques have transformed NMR into a more powerful and versatile method for the structural and dynamic characterization of biomolecules. Current efforts still focus on improving the methodology to increase the number of systems amenable to NMR analysis, to generate better structures and to investigate biomolecular motions in solution.

Carbohydrate Conformation↗

PubMed1994

Differential relationships among the 10-Hz rhythmic discharges of sympathetic nerves with different targets.

Partial coherence analysis was used to remove the influences of the central circuits controlling a sympathetic nerve (as reflected by its discharges) on the coherence of the 10-Hz discharges of other sympathetic nerves in unanesthetized decerebrate or urethan-anesthetized cats. In many cases, partialization reduced but did not eliminate the sharp peak near 10 Hz in the coherence functions relating the discharges of sympathetic nerve pairs. This observation implies that the central sources of the 10-Hz rhythmic discharges of any nerve are not identical to those responsible for the rhythm recorded from any other nerve. Partial coherence analysis also revealed differential relationships among the 10-Hz rhythmic discharges of sympathetic nerves with different targets. Importantly, the pattern of differential relationships observed in one experiment could be the reverse of that in the next. Although the basis for the differential relationships is not yet clear, nonuniform coupling of multiple brain stem 10-Hz oscillators and/or nonuniform cross talk between spinal circuits controlling different sympathetic nerves may be involved.

Animals↗

PubMed1994

Coordination of the cardiac-related discharges of sympathetic nerves with different targets.

Partial coherence analysis was used to remove the influences of pulse-synchronous baroreceptor nerve activity (as reflected by the arterial pulse) on the coherence of the cardiac-related discharges of sympathetic nerve pairs in unanesthetized decerebrate cats. It can be predicted that the peak at the heart rate frequency in the ordinary coherence function relating the discharges of two nerves will be eliminated by either partialization using the arterial pulse or surgical baroreceptor denervation, if the central circuits controlling the nerves share baroreceptor inputs but are not interconnected. Contrary to this prediction, in many experiments the peak was not eliminated by partialization using the arterial pulse. Moreover, partialization often nonuniformly reduced the peaks at the heart rate frequency in the coherence functions for different nerve pairs. These results are consistent with a model of multiple routes over which baroreceptor influences are distributed to the central circuits controlling different sympathetic nerves. Specifically, we propose that the direct route from the baroreceptors to each of the central circuits is complemented by cross talk among the central circuits.

Animals↗

PubMed1994

Chromosome assignment of the human glutathione S-transferase mu 3 gene (GSTM3) to chromosome 1 by gene specific polymerase chain reaction.

Oligonucleotide primers specific for exons 4 and 5 sequences were used to amplify a unique 199-bp fragment in the human GSTM3 gene. Using DNA from a panel of somatic cell hybrids we assigned the GSTM3 locus to chromosome 1p.

Base Sequence↗

PubMed1994

Human ApoA-II inhibits the hydrolysis of HDL triglyceride and the decrease of HDL size induced by hypertriglyceridemia and cholesteryl ester transfer protein in transgenic mice.

The plasma cholesteryl ester transfer protein (CETP) mediates the exchange of HDL cholesteryl esters with triglycerides of other lipoproteins. Subsequent lipolysis of the triglyceride-enriched HDL by hepatic lipase leads to reductions of HDL size and apoA-I content. To investigate a possible modulation of the effects of CETP by apoA-II, human CETP transgenic mice were cross-bred with transgenic mice expressing human apoA-II and, in some cases, human apoA-I and apoC-III (with human-like HDL and hypertriglyceridemia). CETP expression resulted in reductions of HDL and increases in VLDL cholesteryl ester in mice expressing human apoA-II, alone or in combination with apoA-I and apoC-III, indicating that apoA-II does not inhibit the cholesteryl ester transfer activity of CETP. However, CETP expression resulted in more prominent increases in HDL triglyceride in mice expressing both apoA-II and CETP, especially in CETP/apoA-II/apoAI-CIII transgenic mice. CETP expression caused dramatic reductions in HDL size and apoA-I content in apoAI-CIII transgenic mice, but not in apoA-II/AI-CIII transgenic mice. HDL prepared from mice of various genotypes showed inhibition of emulsion-based hepatic lipase activity in proportion to the apoA-II/apoA-I ratio of HDL. The presence of human apoA-II also inhibited mouse plasma hepatic lipase activity on HDL triglyceride. Thus, apoA-II does not inhibit the lipid transfer activity of CETP in vivo. However, coexpression of apoA-II with CETP results in HDL particles that are more triglyceride enriched and resistant to reductions in size and apoA-I content, reflecting inhibition of hepatic lipase by apoA-II. The inhibition of HDL remodeling by apoA-II could explain the relatively constant levels of HDL containing both apoA-I and apoA-II in human populations.

Animals↗

PubMed1994

Potentiation of glucocorticoid receptor-mediated gene expression by heat and chemical shock.

We have examined the effects of heat shock on glucocorticoid receptor (GR)-mediated gene transcription in an L929 cell line derivative (LMCAT2) stably transfected with the mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) reporter plasmid. Exposure of the LMCAT2 cells to heat or chemical shock resulted in a large increase in dexamethasone (Dex)-induced expression of CAT enzyme activity. This potentiation of hormone-induced MMTV-CAT expression was dependent on the magnitude of the stress event and on the Dex concentration, with maximal increases observed for 1 microM Dex after 2 h at 43 C or 2 h at 200 microM sodium arsenite. Heat shock potentiation of MMTV-CAT expression was not seen in an L929 cell derivative devoid of GR or in LMCAT2 cells treated with RU486 antagonist, suggesting that this effect of stress on CAT gene expression was mediated by the GR. Using a quantitative Western blot procedure, the amount of GR protein in the nucleus of cells subjected to combined heat shock and Dex treatment was no greater than the amount of nuclear GR in cells treated with hormone alone, indicating that the stress potentiation effect was not the result of increased nuclear translocation or retention by the GR. In addition, equally strong potentiations of MMTV-CAT expression were observed for cells subjected to heat shock either before or after Dex-mediated translocation of the GR to the nucleus. Thus, the major effect of stress on GR transcription enhancement activity appears to occur after the GR is bound to its high affinity nuclear acceptor sites. We have used a series of MMTV-CAT reporter constructs containing varying portions of the long terminal repeat regulatory region to show that a putative heat shock transcription factor-binding sequence at position -437 of the long terminal repeat is not required for this effect of heat shock on MMTV-CAT expression. A stress-induced increase in hormone-mediated CAT gene expression was observed for a minimal CAT reporter controlled by two synthetic glucocorticoid response elements and a TATA box sequence. Thus, it is unlikely that any DNA-binding transcription factor, other than GR, is required for this effect of stress on transcription by the hormone-bound GR. Based on these results, a model of heat shock enhancement of GR-mediated gene expression is developed in which stress acts on the DNA-bound GR, on a putative heat shock-activated adaptor, or on components of the RNA-polymerase-II complex.

Animals↗

PubMed1994

Impact of annual screening and chemotherapy with praziquantel on schistosomiasis japonica on Jishan Island, People's Republic of China.

The impact of annual screening and treatment with praziquantel on schistosomiasis japonica was examined on Jishan Island in Po Yang Lake, Jiangxi Province. China. Prevalence of infection in the community decreased from 39% in year 1 to 33% in year 3 with a corresponding decrease in the geometric mean egg count from 51 eggs per gram of stool (epg) to 31 epg. The most dramatic changes in infection status and intensity of infection were observed in younger individuals (0-19 years of age). The prevalence of hepatosplenomegaly also significantly decreased, again primarily in younger individuals. No change in the community prevalence of schistosome-induced hepatic fibrosis was observed as determined by ultrasonography. Longitudinal cohort analysis, however, demonstrated significant improvement in treated individuals with advanced hepatic fibrosis. These data indicate that annual screening and treatment had a significant impact on infection status and morbidity and suggest that community therapy may be an effective approach to control schistosomiasis japonica in lake regions and marshlands in China. Further studies are necessary to determine the optimal and most cost-effective approach for drug delivery.

Adolescent↗

PubMed1994

The autocrine regulatory effect of vasoactive intestinal peptide on the growth of human pancreatic carcinoma cells.

In the present study, the effects of VIP on the growth of two human pancreatic carcinoma cell lines PU-PAN-1 and PANC-1 were determined using tritiated thymidine incorporation. VIP receptors, intracellular cAMP and polyamines were investigated. The results indicated that VIP at a concentration of 10(-8) mol/L to 10(-7) mol/L can significantly stimulate the growth of PU-PAN-1 cells but not PANC-1 cells. This effect is dose-dependent and abolished by VIP receptor antagonist, [4-C1-Phe6, Leu17] VIP, suggesting VIP receptors in PU-PAN-1 cells may mediate this effect. VIP can markedly elevate the levels of intracellular cAMP and polyamines in PU-PAN-1 cells, indicating that the growth-promoting effect stimulated by VIP may be via a rapid increase in the biosyntheses of cAMP and polyamines. In addition, the VIP-antibody inhibited the growth of PU-PAN-1 cells in serum-free culture medium. The results above suggested that VIP has an autocrine regulatory effect on this pancreatic carcinoma cell line (PU-PAN-1).

Biogenic Polyamines↗

PubMed1994

65 cases of preserving pylorus pancreatoduodenectomy: experience and problems.

Sixty-five patients with neoplasm (62 cases) or pancreatitis (3 cases) were treated with preserving pylorus pancreatoduodenectomy (PPPD) from 1984 to 1991. One postoperative death occurred. Follow-up studies were performed in 35 patients who had been treated by PPPD or the standard Whipple's procedure; they were questioned carefully concerning clinical symptoms. Further studies were performed in 20 patients with or without pylorus preservation (10 patients, respectively). Nutritional status and gastrointestinal digestive and absorptive functions were evaluated by determination of serum components, gastric analysis, barium emptying time, D-xylose absorption test, 14CO2 breath test, PABA, and other methods. The results demonstrated malnutrition and postgastrectomy syndromes in some patients after the standard Whipple's procedure, but not in those with PPPD. The quality of life was better in the latter. Pylorus preservation may be the main reason for this above difference. Delayed gastric emptying in the early postoperative period was a complication in some patients (21%) treated by PPPD. We recommend PPPD for pancreatoduodenectomy.

Adenocarcinoma↗