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Biomedical subjects

L Gong

Publications and source records attributed to L Gong.

At least 73 records · Page 4Linked to original sources

Chinese contribution to trials on antihypertensive therapy.

LACK OF TRIAL DATA ON NEW ANTIHYPERTENSIVE AGENTS: The present debate concerning the use of new classes of antihypertensive agents in general and calcium antagonists in particular, is due to the fact that for most of the agents, there is a lack of data from major clinical trials with cardiovascular outcomes. CONTRIBUTION OF CHINESE CLINICAL TRIAL DATA: The present review summarizes and qualifies the prospective clinical trial data obtained in China which were performed with calcium antagonists and indapamide. These results need to be reviewed critically for their weaknesses as well as strengths, so that the data can be used to improve present knowledge of antihypertensive therapy.

Antihypertensive Agents↗

Shanghai trial of nifedipine in the elderly (STONE).

OBJECTIVE: To assess the effectiveness of nifedipine treatment in elderly hypertensives. METHODS: A single-blind trial was conducted under the direction of the Shanghai Institute of Hypertension in 1632 subjects aged 60-79 years alternatively allocated to either nifedipine or placebo after a 4-week placebo run-in period between 1987 and 1990 with mean follow-up of 30 months. Clinical events and risk modification were analysed in collaboration with the University of Montreal. Seventy-four patients with severe hypertension were reallocated to active nifedipine treatment after placebo run-in. RESULTS: Cox's proportional hazards model accounting for covariates demonstrated a highly significant decrease in the probability of events: 'original treatment assignment' analysis indicated that 77 events occurred in the placebo and 32 in the nifedipine group. Similar significances were achieved with 'actual treatment' or 'changes excluded' (excluding reallocated subjects) analyses. A significant reduction in relative risk was observed for strokes and severe arrhythmia with an overall decrease from 1.0 to 0.41 (95% confidence interval 0.27-0.61). CONCLUSION: Nifedipine treatment diminished the number of severe clinical outcomes in elderly hypertensives significantly.

Aged↗

Translational control of puf operon expression in Rhodobacter sphaeroides 2.4.1.

The puf operon of Rhodobacter sphaeroides 2.4.1 encode the beta- and alpha-polypeptides of the B875 complex, the L and M polypeptides of the reaction centre and the pufX gene product. A previous report from the authors' laboratory indicated the potential existence of a 20-codon open reading frame (orfK, now designated pufK) located immediately upstream of the pufB structural gene. It is now demonstrated that pufK is translated in vivo and that the specific levels or nature of the rare codons within pufK affect the expression of pufK. Using a series of pufK-specific mutations, both in trans as lacZ translational fusions and incorporated into the genome in single copy, evidence has been obtained that translation initiation through pufK may be essential to translation of pufB. Further, the abundance, quality and distribution of rare codons within pufK may serve to 'gate' the entry of ribosomes at pufB. The data also suggest that translation of pufB is uncoupled from that of pufA, with the latter capable of being produced in excess of the former. It is also revealed that the secondary structure at the 5' end of the large and small puf transcripts may play a role in mRNA stability and that stability of the small puf transcript is independent of translation.

Amino Acid Sequence↗

Oligonucleotides induce apoptosis restricted to the t(14;18) DHL-4 cell line.

Most human follicular B-cell lymphomas are associated with t(14;18) chromosome translocation that joins the bcl-2 gene with the IgH locus. This hybrid gene causes upregulation of BCL-2 protein expression, endowing cells with survival advantage. Although early BCL-2 overexpression is definitely responsible for immortalization/transformation, its exact role in the overt transformation as well as in the maintenance of the tumor phenotype is not known. The capacity of oligodeoxynucleotides (ODN) to modulate gene expression specifically has been exploited to downregulate the overexpression of BCL-2 protein in the SU-DHL-4 human follicular B-cell lymphoma line by the use of sense ODN or antisense ODN or antisense ODN designed to encompass the unique nucleotide sequence in the fusion region of the hybrid transcript. The specific downregulation of the bcl-2 transcript and of the relevant BCL-2 protein in the treated cells activated programed cell death and inhibited growing cells. The antitumor activity was restricted to the DHL-4 cell line carrying the specific nucleotide sequence at the bcl-2/IgH joining region. Thus, DHL-4 lymphoma cells derived from the acute phase of human follicular B-cell lymphoma, although endowed with additional activated oncogenes, were growth inhibited by bcl-2 downregulation with additional activated oncogenes, were growth inhibited by bcl-2 downregulation in a genetically restricted fashion. The biological activity was exerted exclusively by ODNs synthesized in the sense orientation. The sense ODNs have been proposed to anneal the hybrid bcl-2/IgH antisense RNA as identified in this study.

Amino Acid Sequence↗

Terminally L-modified oligonucleotides: pairing, stability and biological properties.

An oligodeoxynucleotide (ODN), capable of reducing the growth of human B lymphocytes carrying the t(14;18) chromosome translocation, was prepared in different 'chemical versions': unmodified phosphodiester, phosphorothioate and phosphodiester capped with L-2'-deoxycytidine. Their binding affinity to the complementary synthetic target was studied by the melting point assay. The ODNs, administered to DOHH2 cells, were compared for stability in the culture medium, cellular uptake, time course of the intact sequence concentration within the cell and ability to inhibit cell growth. The 5', 3'-L-capped derivative and the phosphorothioate had comparable potency, superior to that of the unmodified ODN, in agreement with the concentration of undegraded ODNs within the cell.

Antineoplastic Agents↗

Dopamine induces apoptotic cell death of a catecholaminergic cell line derived from the central nervous system.

Dopamine produces a time- and dose-dependent increase in cell death in a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system. Cell death also occurred after treatment with the catecholamines L-dihydroxyphenylalanine, norepinephrine, epinephrine, and isoproterenol, as well as the neurotoxic compound 6-hydroxydopamine. Cell death is not receptor mediated because selective noradrenergic and dopaminergic receptor agonists had no effect on CATH.a cell viability. Dopamine induces apoptotic cell death as indicated by DNA fragmentation measured by gel electrophoresis and by flow cytometric analysis. Apoptosis seems to be produced by dopamine autoxidation, because intracellular peroxides increase after dopamine treatment and cell death can be inhibited by catalase and N-acetylcysteine. N-acetylcysteine produced a dose-dependent decrease in dopamine-induced cell death; this correlated with a decrease in peroxide formation. In addition, antisense to the antioxidant protein bcl-2 increases the sensitivity of CATH.a cells to dopamine-induced cell death. These findings indicate that the oxidative products of dopamine cause neurotoxicity through apoptosis.

Animals↗

Long-term blood pressure control in older Chinese patients with isolated systolic hypertension: a progress report on the Syst-China trial.

This report on the ongoing double-blind placebo-controlled Syst-China trial investigated whether antihypertensive drug treatment based mainly on a calcium entry blocker and a converting enzyme inhibitor, would be suitable for maintaining long-term blood pressure (BP) control in older Chinese patients (average age: 67 years) with isolated systolic hypertension (systolic pressure 160-219 mm Hg and diastolic pressure < 95 mm Hg). Active treatment consisted of nitrendipine (10- 40 mg/day) with the possible addition of captopril (12.5- 50 mg/day) and hydrochlorothiazide (12.5-50 mg/day), as necessary to reduce systolic pressure to a level of 150 mm Hg or lower and by at least 20 mm Hg. Matching placebos were used in the control group. This progress analysis was restricted to BP control up to 3 years of follow-up. The placebo (n = 1134) and active treatment n = 1245) groups had similar characteristics at enrolment. The sitting BP averaged 170/86 mm Hg. Systolic pressure fell (P < 0.001) on average 8 mm Hg more on active treatment than on placebo and diastolic pressure 3 mm Hg more. Fewer patients remained on monotherapy in the placebo than in the active treatment group (P < 0.001); on placebo the second and third line medications were started more frequently (P < 0.001). This progress report showed that significant BP reduction can be achieved and maintained in older Chinese patients treated with a calcium antagonist, associated with a converting-enzyme inhibitor and a thiazide, as necessary. Whether this BP reduction would result in a clinically meaningful decrease of cardiovascular complications is still under investigation.

Aged↗

Beneficial effects of captopril on prognosis in patients with acute myocardial infarction. Shanghai Secondary Prevention of Acute Myocardial Infarction Study Group.

OBJECTIVES: To assess the effects of early and long-term angiotensin-converting enzyme inhibitor treatment with captopril on clinical outcome in patients with acute myocardial infarction (AMI). METHODS: Eight hundred and twenty-two patients with AMI who were hospitalised within 72 hours of symptoms and had no cardiogenic shock were randomly allocated to captopril (n = 478, Group I) and conventional treatment (n = 344, Group II). Cardiac events including congestive heart failure, reinfarction, severe arrhythmias and cardiac death during hospitalization and follow-up period (average 20 months) were determined. RESULTS: The overall mortality rate during hospitalization was lower in group I than in group II (P = 0.0001), this was true for patients with anterior (P = 0.0003), inferior (P = 0.0411) and anterior inferior AMI (P = 0.0232). During follow-up, despite similar occurrence rate of reinfarction and severe arrhythmias in the two groups, the mortality rate (P = 0.0324) and total cardiac event rate (P = 0.055) were lower in group I than in group II. CONCLUSIONS: After AMI, early and long-term treatment with captopril exerts a beneficial effect on the prognosis of patients.

Aged↗

Abnormal coronary flow reserve in patients with angina pectoris and hypertensive left ventricular hypertrophy.

OBJECTIVE: To assess coronary flow reserve using a computer-assisted method with intracoronary papaverine in patients with angina pectoris. PATIENTS AND METHODS: Coronary arterial diameter, cross-sectional area and blood flow velocity were measured during coronary arteriography before and after intracoronary papaverine in 26 control subjects, 45 patients with significant coronary artery disease (> 50% luminal narrowing), 16 patients with syndrome X and 14 patients with hypertension and left ventricular hypertrophy (LVH). RESULTS: After intracoronary administration of papaverine, proximal diameter, cross-sectional area, blood velocity, flow volume and reserve capacity of both left anterior descending and right coronary arteries were lower in patients with significant coronary stenosis than in the controls. Despite similar changes in diameter and cross-sectional area, the blood velocity, flow volume and reserve capacity of the two vessels were also lower in patients with syndrome X than in the controls. In 14 patients with hypertension and LVH, although the blood velocity and flow volume were augmented for the two arteries and did not differ from those in the controls, the flow reserve was reduced because of higher baseline blood velocity and flow volume. CONCLUSIONS: Coronary flow reserve is reduced in patients with coronary artery disease, syndrome X or hypertensive LVH, which may be related to abnormal changes at different levels of the coronary vasculature or resting flow states.

Angina Pectoris↗

Structural alterations of resistance vessels of spontaneously hypertensive rats and protective effects of captopril.

OBJECTIVE: To observe the structural alterations of resistance vessels in spontaneously hypertensive rats (SHRs) and to evaluate the effects of captopril on them. METHODS: 15-week-old male SHRs were treated with oral captopril (100 mg/kg/day) for 12 weeks. Age- and sex-matched SHRs and Wistar-Kyoto rats (WKY) were fed under the same conditions without captopril administration for the same duration. All rats were killed at the age of 27 weeks. The structural parameters included media width, lumen diameter, media-lumen ratio, vascular collagen area (VCA) and vascular collagen density (VCD). The media width, lumen diameter and media-lumen ratio were measured in hhematoxylin and eosin staining sections under a direct light microscope and VCA and VCD in picrosirius red staining sections under a polarizing light microscope. All the values were processed with a computer image analyzer. RESULTS: There were thicker media width, smaller lumen diameter, higher media-lumen ratio and larger VCA in untreated SHRs than in WKY. Captopril inhibited media thickening, with lumen diameter decreasing, media-lumen ratio increasing and VCA enlarging. There was no significant difference in VCD among the three groups. CONCLUSIONS: Adverse structural alterations occur in resistance vessels of SHRs and captopril may prevent their progression.

Angiotensin-Converting Enzyme Inhibitors↗

Clinical significance of complete left bundle branch block in dilated cardiomyopathy.

Clinical, electrocardiographic and echocardiographic findings in 64 patients with dilated cardiomyopathy were restrospectively studied. Compared with 51 patients without complete left bundle branch block (CLBBB), 13 patients with CLBBB had higher New York Heart Association (NYHA) functional class (P < 0.05), increased left ventricular end-diastolic and end-systolic diameters (P < 0.002) and myocardial mass (P < 0.02), severe mitral regurgitation (P < 0.01) and higher mortality rate (P < 0.04). Multivariate stepwise regression analysis revealed that the presence of CLBBB was an independent prognostic factor for patients with dilated cardiomyopathy.

Adult↗

Abnormal left ventricular systolic and diastolic functional response to isometric exercise in idiopathic dilated cardiomyopathy: beneficial effect of captopril.

In 19 patients with idiopathic dilated cardiomyopathy and symptoms of congestive heart failure, left ventricular (LV) systolic performance and diastolic velocity profiles were assessed by two- dimensional echocardiography and pulsed wave Doppler at rest and during handgrip exercise before and ninety minutes after administration of captopril (mean dose 25 +/- 12mg; range 12.5-50mg). Although heart rate and blood pressure increased similarly during handgrip exercise before and after captopril treatment, both were lower with handgrip exercise during captopril treatment. The results from this study indicated that acute angiotension converting enzyme inhibition with captopril reduces preload and afterload and ameliorates handgrip exercise-induced LV systolic and diastolic filling dysfunction in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy.

Adult↗

[Clinical analysis of anaerobic septicemia in 26 patients with extensive burn].

To understand the incidence and importance of anaerobic infection, the aerobic and anaerobic blood culture were carried out simultaneously in 127 patients with extensive burns (TBSA > 50%). Among 39 patients with positive culture, 26 had anaerob growth in blood culture. The total incidence rate of anaerobic septicemia was 20.4%. 61 strains (9 species) of anaerobes were isolated from blood specimens. The predominant anaerobes were Peptococcus (37.7%) and B. fragilis (36.1%). 20 (76.9%) were mixed infection of aerobes and anaerobes. The others thers suffered from combined infection of B. Fragilis and peptococcus combined infection. Finally, 19 patients survived and 7 died (26.9%). The sensitive tests showed that the effective drugs were metronidazot, chloramycin, and lincomycin. These data suggested that the septicemia of extensive burn patients is often caused by anaerobes. Therefore, anaerobe plays an important role in burn infection.

Adolescent↗

Knowledge-based medical image analysis and representation for integrating content definition with the radiological report.

Technology breakthroughs in high-speed, high-capacity, and high performance desk-top computers and workstations make the possibility of integrating multimedia medical data to better support clinical decision making, computer-aided education, and research not only attractive, but feasible. To systematically evaluate results from increasingly automated image segmentation it is necessary to correlate them with the expert judgments of radiologists and other clinical specialists interpreting the images. These are contained in increasingly computerized radiological reports and other related clinical records. But to make automated comparison feasible it is necessary to first ensure compatibility of the knowledge content of images with the descriptions contained in these records. Enough common vocabulary, language, and knowledge representation components must be represented on the computer, followed by automated extraction of image-content descriptions from the text, which can then be matched to the results of automated image segmentation. A knowledge-based approach to image segmentation is essential to obtain the structured image descriptions needed for matching against the expert's descriptions. We have developed a new approach to medical image analysis which helps generate such descriptions: a knowledge-based object-centered hierarchical planning method for automatically composing the image analysis processes. The problem-solving steps of specialists are represented at the knowledge level in terms of goals, tasks, and domain objects and concepts separately from the implementation level for specific representations of different image types, and generic analysis methods. This system can serve as a major functional component in incrementally building and updating a structured and integrated hybrid information system of patient data.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial Intelligence↗

Neonatal 6-hydroxydopamine and adult SKF 38393 treatments alter dopamine D1 receptor mRNA levels: absence of other neurochemical associations with the enhanced behavioral responses of lesioned rats.

To study potential biochemical correlates of dopamine (DA) and serotonin receptor supersensitivity, rats were lesioned at 3 days after birth with 6-hydroxydopamine (6-OHDA; 67 micrograms in each lateral ventricle; desipramine pretreatment, 20 mg/kg i.p., 1 h) and then sensitized with the DA D1 agonist, SKF 38393 HCl (3.0 mg/kg i.p. per day) either ontogenetically (daily, for 28 consecutive days from birth) and/or in adulthood (four weekly injections, 6-9 weeks from birth). Controls received vehicle in place of 6-OHDA or SKF 38393. Enhanced locomotor responses were observed after SKF 38393 at 6 weeks, only in rats that received SKF 38393 + 6-OHDA in ontogeny. Locomotor responses were further enhanced in this group after the last of four weekly SKF 38393 injections at the 9th week. These weekly SKF 38393 treatments also produced enhanced responses in 6-OHDA rats that did not receive SKF 38393 in ontogeny. When striata were studied at 11 weeks, the percentages of high and low affinity DA D1 binding sites were not altered. Basal as well as DA-, NaF-, and forskolin-stimulated adenylyl cyclase activities also were not changed. Dot blot analysis showed that there was a reduction of mRNA levels for DA D1, but not serotonin1C, receptors in the 6-OHDA groups. However, SKF 38393 at 6-9 weeks eliminated this alteration. Based on these findings it can be proposed that supersensitization may be a consequence of altered neuronal cross talk rather than an imbalance of receptor elements per se.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

The Q gene of Rhodobacter sphaeroides: its role in puf operon expression and spectral complex assembly.

The Q gene of the facultative photoheterotroph Rhodobacter sphaeroides, localized immediately upstream of the oxygen- and light-regulated puf operon, encodes a 77-amino-acid polypeptide. The 5' and 3' ends of the 561-bp Q transcript were determined. To gain insight into the role of the Q gene product, a number of Q mutations were constructed by oligonucleotide-directed mutagenesis and subsequent substitution of the mutated form of the gene in single copy for the chromosomal copy via homologous recombination. The resulting mutants can grow photosynthetically, with the exception of QSTART, in which the initiation codon for the Q protein was altered. Spectral analysis of the intracytoplasmic membranes showed that one of the missense mutants (QdA) was deficient in the formation of detectable B875 light-harvesting complex (LHC), whereas deletion of the stem-loop structure (Qloop) failed to form B800-850 LHC when grown anaerobically either in the dark or under light intensity of 100 W/m2. Other missense mutants (QuA and QuB) contained either more B800-850 LHC or more B875 LHC, respectively, than the wild type. Although the levels of puf and puc transcripts isolated from QSTART grown anaerobically on succinate-dimethyl sulfoxide in the dark were comparable to wild-type levels, no B875 spectral complex was detected and there was a greater than 90% reduction in the level of the B800-850 pigment-protein complex. It has also been confirmed that the ultimate cellular levels of either the B875 or B800-850 spectral complexes can vary over wide limits without any change in the level(s) of complex specific transcripts. When the wild-type Q gene was reintroduced in trans into the Q mutations, QSTART was able to grow photosynthetically and both B800-850 and B875 spectral complexes were formed in either QdA or Qloop. Finally, we demonstrated that the level of each puf-specific mRNA behaves independently of one another as well as independently of the level(s) of Q gene-specific mRNA. These results are compatible with the existence of regulatory sequences affecting the puf mRNA level(s) being localized within the Q structural gene. These results suggest that Q-specific expression is uncoupled from puf-specific transcription and that the Q protein is not involved in the regulation of transcription of the puf operon but is directly involved in the assembly of both the B875 and B800-850 pigment-protein complexes.

Amino Acid Sequence↗

[Comparative study of single strand conformation polymorphism of 4.5S RNA gene in enterobacteria].

A recently developed technique, non-isotopic single strand conformation polymorphism analysis (PCR-SSCP), was applied to study the conserved feature of 4.5S RNA gene in enterobacteria. The 4.5S RNA gene was amplified by the polymerase chain reaction, using the template DNA extracted respectively from five strains of Escherichia coli and three strains of different genera in Enterobacteriaceae, i.e. Proteus vulgaris, Serratia marcescens and Enterobacter aerogenes. The PCR products were then carried out SSCP analysis. The experimental results showed that there seemed to be no detectable differences in the size and single strand conformation of 4.5S RNA genes from above strains, except the negative strand conformation of Enterobacter aerogenes. Thus it can be seen that the secondary structures of 4.5S RNA gene in enterobacteria are quite conservative.

Base Sequence↗