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Biomedical subjects

D Sun

Publications and source records attributed to D Sun.

At least 307 records · Page 17Linked to original sources
PubMed1995

Flow-dependent dilation and myogenic constriction interact to establish the resistance of skeletal muscle arterioles.

OBJECTIVE: To test the hypothesis that the diameter of skeletal muscle arterioles is determined by the interaction of responses elicited by intravascular pressure and flow. METHODS: Experiments were conducted on isolated, cannulated, first-order arterioles of cremaster muscle of male Wistar rats. The diameter of arterioles was followed by videomicroscopy. Perfusion pressures and flows were controlled. RESULTS: In the absence of perfusate flow, increases in perfusion pressure (from 0 to 120 mm Hg), after initial dilation, elicited endothelium independent constrictions of arterioles. At 60 mm Hg of perfusion pressure, the active diameter of vessels was 84.9 +/- 1.9 microns. The passive diameter of arterioles (Ca2(+)-free solution)was 150.6 +/- 2.4 microns. Increases in perfusate flow resulted in a significant upward shift in the pressure-diameter curves; in the presence of perfusate flows of 20, 40, and 60 microL/min, the constriction of the vessels at a pressure of 60 mm Hg was attenuated by 25.1 +/- 3.9%, 35.2 +/- 3.0%, and 46.8 +/- 4.4%, respectively. In contrast, the corresponding diameter of arterioles at perfusate flows of 10 to 60 microL/min was significantly reduced when perfusion pressure was increased from 60 to 80 and 100 mm Hg (at a flow of 60 microL/min) by 12.0 +/- 4.3% and 37.1 +/- 2.8%, respectively. Hence, both flow- and shear stress-diameter curves were significantly shifted downward when perfusion pressure increased from 60 to 100 mm Hg. CONCLUSION: These results demonstrate that an interplay between pressure and flow-sensitive mechanisms is an important determinant of the arteriolar resistance in skeletal muscle.

Animals↗
PubMed1995

Antitat gene therapy: a candidate for late-stage AIDS patients.

Antitat is an autoregulated gene expressing an inhibitory RNA with dual function: it sequesters the Tat protein by polymeric-TAR and blocks the translation of the Tat messenger RNA by antisense-Tat. Using human T cell lines and peripheral blood lymphocytes as the in vitro target, we have previously shown that antitat is an effective long-term suppressor of HIV-1, including 'field' isolates. To assess the efficacy of this inhibitory gene better in the setting of an infected individual with late-stage AIDS, we examined its antiviral activity in an in vivo established infection. Peripheral blood mononuclear cells isolated from AIDS patients were transduced with replication defective retroviral vectors carrying the antitat gene. In the absence of cell selection, the antitat gene blocked virus replication and allowed infected CD4+ T cells to expand in culture. These results suggest that antitat gene therapy may be beneficial to block HIV-1 replication and reconstitute the immune system of late-phase AIDS patients. We introduced a new parameter, CRF, which defines the effectiveness of the ex vivo gene therapy treatment of AIDS patients. Antitat treatment was efficient in cells of all patients regardless of viral quasispecies, however, it was most potent in severely immunocompromised individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Relationship of LDLR gene polymorphism and NIDDM in Chinese.

Genomic DNA was extracted from peripheral blood lymphocytes of 105 healthy and 75 NIDDM Chinese subjects. The fragment located in exon 13 of the low density lipoprotein receptor (LDLR) gene was amplified by polymerase chain reaction (PCR), and digested with restriction enzyme HincII. LDL, TC and TG levels were measured in all subjects. Investigations were conducted to explore the correlation between the HincII RFLP of LDLR gene and NIDDM in the Chinese population. The results showed that no significant correlation existed between this RFLP locus and NIDDM. Marked differences were found, however, between the genotype distribution of low LDL level subgroups of NIDDM patients and normal controls. It was inferred that the H1 allele might be associated with high blood cholesterol levels, and the H2 allele with low cholesterol levels. Disturbances of lipid metabolism occur frequently in diabetes mellitus. This study suggested that differences in LDLR genotypes may affect the phenotypes of lipid metabolism.

Adult↗
PubMed1995

The population association of glucokinase gene with type 2 (noninsulin-dependent) diabetes mellitus in Chinese.

The association of gluckinase (GCK) gene with type 2 (non-insulin-dependent) diabetes mellitus was investigated in 168 Chinese subjects (85 unrelated type 2 diabetics and 83 non-diabetic controls). The microsatellite polymorphism marker, GCK-5', was amplified with polymerase chain reaction. Four alleles were observed in Chinese population with length varying from 137bp to 143bp and the most common one being the 139bp allele 3. In comparison with non-diabetics, allele 4 was significantly increased in type 2 diabetes (10% versus 38, respectively; X2 = 6.773, P = 0.009); genotype 44 and 4X (X denotes any allele other than allele 4) were significantly increased in type 2 diabetes (16% versus 6% respectively; X2 = 6.439, P = 0.011). The frequency difference was also shown in overweight/obese subgroup comparison (X2 = 7.718, P = 0.021), but not in lean/normal-weight subgroup comparison. No differences of age of onset and frequency of positive family history were observed between type 2 diabetic patients with genotype 44 or 4X and those with XX. The risk for type 2 diabetes in Chinese with genotype 44 or 4X was about 3.5 times higher than in Chinese with genotype XX. Therefore, GCK gene was associated with Chinese type 2 diabetes.

Adult↗
PubMed1995

Carbon dioxide volume and intra-abdominal pressure determination before the creation of a pneumoperitoneum.

Laparoscopic surgery generally is regarded as a safe procedure when a preset pressure is used in the carbon dioxide insufflator. However, a fixed pressure setting is not appropriate when insufflating a very large or a very small abdomen. Presently, extrapolation from the commonly used 15 mm Hg to an appropriate and safe pressure cannot be easily determined except by a crude trial and error method. We developed an anthropometric formula to calculate the total abdominal cavity capacity and the corresponding pressure necessary to obtain safe pneumoperitoneum. This anthropometric formula calculates the total abdominal capacity by measuring one diameter from the symphysis pubis to the xyphoid bone, a second diameter as half the initial measurement, and a third diameter by dividing the waist measurement (minus an estimated percentage of body fat) and dividing that product by pi. The product of the three diameters is then multiplied by a constant (K = 0.5). We studied prospectively 20 patients whose indications for laparoscopic surgery necessitated creation of a pneumoperitoneum. The patients were divided into two groups: group A (n = 10), patients who were observed with the intra-abdominal pressure fixed at 15 mm Hg while recording the amount of distension produced in the abdominal cavity during creation of the pneumoperitoneum; and group B (n = 10) in whom pneumoperitoneum was obtained based on the initial volume of carbon dioxide-insufflation previously calculated using our formula. Based on our observations, we conclude that this anthropometric formula can be used successfully in predicting a safe level of insufflation in relation to the patient's size.

Abdomen↗
PubMed1995

[High yield techniques for bupleurum falcatum L].

The growth of plants may be controlled by clipping the aerial part. This may increase the yield of Bupleurum falcatum. Different methods of cultivation may result in different outputs of crude drugs. Compared with land plotting, deep ploughing and high ridging may increase the root weight of one-year-old plant by 28% and 50% respectively.

Plants, Medicinal↗
PubMed1995

[Cost-benefit analysis on Malayan filariasis control in Miaoxi Township, Huzhou City, Zhejiang Province during 1964-1987].

The methods adopted in this paper were as follows: (1) The cost of the filariasis control was estimated to be direct cost and indirect cost; (2) Using the reduction rate of acute inflammatory attack as the measurable indicator of control effectiveness; (3) Estimating the case number of acute inflammatory attack occurred after control year by year basing on the goodness by fitting in the reduction trend of acute inflammatory attack with hyperbola formula; (4) Assuming that the case number of acute inflammatory attack would be relatively stable at the same level of pre-control if filariasis control measures were not implemented; (5) The benefit from the filariasis control was estimated by transforming the increasing man-working day and saving the medicine expenses of patients due to the reduction of acute inflammatory attack. By allowing seven percent discount on cost and benefit, the total cost was 21,182 Yuan, the total benefit was 119,859 Yuan, the ratio of cost-benefit was 1:5.7, implying that putting in one Yuan to filariasis control in this township may gain benefit 5.7 Yuan.

Animals↗
PubMed1995

[An eight-year prospective study on 163 cases of hepatitis C].

To explore the characteristics of hepatitis C in China, one hundred and sixty three cases of hepatitis C were followed for 8 years. The rates of abnormal alanine aminotransferase (ALT) were 100%, 73%, 57%, 37% and 28% in less than one, 1, 2, 5 and 8 years after the onset respectively. Abnormality of ALT might be persistent or fluctuating, and the latter type accounted for about 1/3 to 1/2 of the cases. The positive rates of anti-hepatitis C virus (HCV) were 56%, 93%, 94%, 96%, 97%, 93% and 83% in less than two, 2-6, 7-12 months and 1, 2, 5 and 8 years after the onset respectively. Negative conversion of anti-HCV was found only in a few patients whose ALT had returned to normal level and the rates of negative conversion for them were 10%, 8%, 16%, and 22% in 1, 2, 5 and 8 years after the onset. Positive rate of HCV-RNA, detected with nested PCR 8 years after the onset was 84% for patients who still showed positive anti-HCV and there was no significant difference between patients with abnormal (80%) and normal ALT (85%) levels. Genotype II accounted for 93% of the cases. No patient developed hepatocellular carcinoma or decompensated cirrhosis after a follow-up of eight years.

Adolescent↗
PubMed1995

[Surgical treatment of undifferentiated esophageal carcinoma].

From 1961 through 1983, a total of 3,804 cases with carcinoma of esophagus underwent surgical resection of cancer at Shanghai Chest Hospital. Thirty-nine of them were primary undifferentiated esophageal carcinoma (UEC) with an incidence of 1%. In 97% of the cases, the lesions were located at the mid- and lower-esophagus. All cases underwent tumor resection and esophagogastrostomy, with an operative complication rate of 10%, and mortality rate of 13%. Follow-up until December 1994, all patients were dead. 42% of the cases died within 6 months, another 42% of the cases died within 7-24 months, with a median survival period of 7 months only. The postoperative 5-year survival rate was 15%. To improve the therapeutic results, preoperative radiotherapy and postoperative adjuvant therapy are needed.

Adult↗
PubMed1995

[Treatment of ototoxic auditory damage caused by kanamycin with electroacupuncture at different acupoints].

We adopted the technique and method of integrating the morphology with function to select the effective acupoints for treatment of deafness. The results show that: (1) Tinggong (SI 19), Yifeng (TE 17), Waiguan (TE 5), Shenshu (UB 23), Sanyinjiao (SP 6) and Zhubin (KI 9) etc. are the effectine acupoints for the treatment of ototoxic auditory damage caused by drug, especially, the effect of Tinggong, Sanyinjiao and Zhubin etc, is much better; (2) electroacupuncture can promote audibility, improve SDH activity and relieve progressing injury of auditory hair cells, (3) FFR method has an important significance in the determination of ototoxic damage caused by drug.

Animals↗
PubMed1994

Binding of Sp1 to the 21-bp repeat region of SV40 DNA: effect of intrinsic and drug-induced DNA bending between GC boxes.

The effect of the antitumor antibiotic (+)-CC-1065 on the binding of Sp1 to the 21-bp repeats of SV40 DNA has been investigated. (+)-CC-1065 alkylates N3 of adenine in DNA and resides in the minor groove. As a consequence of alkylation of the two 5'-AGTTA* sequences (* indicates covalent modification site), which reside between GC boxes III and IV, and boxes V and VI, protein binding to the 3' sites is completely abolished and there is a significant decrease in Sp1 binding to the other regions. The effect of substituting A5 tracts for the (+)-CC-1065-bonding sequence was intermediate between the unmodified 5'-AGTTA* and the drug-modified sequences. It is proposed that a structural distortion of DNA associated with stiffening of the helix induced by the drug-adduct formation is primarily responsible for the inhibition of binding of Sp1 molecules to 21-bp repeats, rather than steric hindrance due to the occupancy by drug molecules of the minor groove within that region.

Base Sequence↗
PubMed1994

Hydroxyurea as an inhibitor of human immunodeficiency virus-type 1 replication.

Hydroxyurea, a drug widely used in therapy of several human diseases, inhibits deoxynucleotide synthesis--and, consequently, DNA synthesis--by blocking the cellular enzyme ribonucleotide reductase. Hydroxyurea inhibits human immunodeficiency virus-type 1 (HIV-1) DNA synthesis in activated peripheral blood lymphocytes by decreasing the amount of intracellular deoxynucleotides, thus suggesting that this drug has an antiviral effect. Hydroxyurea has now been shown to block HIV-1 replication in acutely infected primary human lymphocytes (quiescent and activated) and macrophages, as well as in blood cells infected in vivo obtained from individuals with acquired immunodeficiency syndrome (AIDS). The antiviral effect was achieved at nontoxic doses of hydroxyurea, lower than those currently used in human therapy. Combination of hydroxyurea with the nucleoside analog didanosine (2',3'-dideoxyinosine, or ddl) generated a synergistic inhibitory effect without increasing toxicity. In some instances, inhibition of HIV-1 by hydroxyurea was irreversible, even several weeks after suspension of drug treatment. The indirect inhibition of HIV-1 by hydroxyurea is not expected to generate high rates of escape mutants. Hydroxyurea therefore appears to be a possible candidate for AIDS therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cooperative bending of the 21-base-pair repeats of the SV40 viral early promoter by human Sp1.

The overall structural features of the multimeric complex between Sp1 and the 21-base-pair repeat of the early promoter region of SV40 DNA have been determined using hydroxyl-radical footprinting; (+)-CC-1065, a sequence-specific minor groove bending probe; and circularization experiments. The results show that the 21-base-pair repeat region has an intrinsically in-phase bent structure that is stabilized upon saturation Sp1 binding by protein-DNA and protein-protein interactions to produce a looping structure. The direction of the Sp1-stabilized bending of DNA occurs into the minor groove and is localized between each of the Sp1 binding sites. These results are used as the basis to propose a looping structure for the multimeric Sp1 21-base-pair repeat region of SV40 DNA. Last, these results provide a rationale for the recently observed inhibition of basal transcriptional levels by site-specific triple-helical DNA complexes.

Base Sequence↗
PubMed1994

Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells.

Gene-expression modulator 91 (GEM91) is a 25-nt antisense oligodeoxynucleotide phosphorothioate complementary to the Gag mRNA of human immunodeficiency virus type 1 (HIV-1). Cellular uptake and intracellular distribution of GEM91 within cells suggest that this oligomer is readily available for antisense activity. GEM91 inhibited HIV-1 replication in a dose-dependent and sequence-specific manner. In a comparative study, 2 microM GEM91 was as effective as 5 microM 3'-azido-3'-deoxythymidine in blocking virus replication during the 28-day treatment of an HIV-1-infected T-cell line. GEM91 also completely inhibited (> 99%) the growth of three different HIV-1 isolates in primary lymphocytes and prevented the cytopathic effect of the virus in primary CD4+ T cells. Similarly, treatment with GEM91 for 3 weeks of HIV-1/BaL-infected primary macrophages blocked virus replication. Based on GEM91 anti-HIV-activity, safety, and pharmacokinetic profile in animals, a clinical trial was started using this compound as an antisense oligonucleotide drug for the treatment of the acquired immunodeficiency syndrome.

Antigens, CD↗
PubMed1994

A Rev-inducible mutant gag gene stably transferred into T lymphocytes: an approach to gene therapy against human immunodeficiency virus type 1 infection.

One strategy for somatic gene therapy for human immunodeficiency virus type 1 (HIV-1) infection is based on the regulated expression of dominant negative mutants of the HIV-1 gag gene. To limit expression of the mutant Gag polypeptide to HIV-1-infected cells, we have constructed a replication-defective retroviral vector that contains a Rev-responsive element. By using this construct we have obviated problems that can be associated with constitutive expression of an exogenous gene, an important step toward developing a human therapy. In uncloned T lymphocytes infected (transduced) with this retroviral construct, HIV-1 replication was inhibited by 94% with a concomitant decrease in the cytopathic effects of the virus. In addition, simian immunodeficiency virus (SIV) replication was also shown to be significantly inhibited, suggesting that this mutant Gag protein may have antiviral efficacy against a broad range of primate lentiviruses and that an SIV/macaque model can be used for further in vivo studies. These results have important implications in assessing the potential of somatic gene therapy in the treatment of HIV-1 infection.

Amino Acid Sequence↗
PubMed1994

Extracellular human T-cell lymphotropic virus type I Tax protein induces cytokine production in adult human microglial cells.

Tropical spastic paraparesis (HAM/TSP) is caused by human T-cell lymphotropic virus type I (HTLV-I) infection. Although the virus infects T cells in vivo and is capable of infecting microglia in vitro, the inflammatory demyelination has not been linked to virus in central nervous system tissue. Thus, indirect mechanisms (e.g., cytokines) could be involved in demyelination and inflammation. The ability of HTLV-I Tax protein to induce tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in primary adult human microglia and peripheral blood macrophages (PBMs) was examined by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction (RT-PCR). Tax (20 ng/ml) induced TNF-alpha in microglia (from undetectable or low basal levels to 215-1,075 pg/ml, mean 576 +/- 375 pg/ml, n = 4) and in PBMs (70-1,900, mean 646 +/- 844 pg/ml, n = 4). This induction was dose dependent, Tax specific, and maximal at 8 hours after stimulation. IL-6 levels in microglia increased from a basal level of 368 +/- 194 to 664 +/- 270 pg/ml 24 hours after Tax stimulation. In contrast, IL-1 beta levels were modestly induced (< or = 26 pg/ml). An increase in mRNA levels of the three cytokines was observed by semiquantitative RT-PCR (TNF-alpha = 28-fold; IL-6 = 5.6-fold; IL-1 beta = 3.6-fold). Thus, in HAM/TSP, extracellular Tax released from infiltrating T cells could induce cytokine release by microglia and contribute to demyelination and inflammation in the absence of detectable virus.

Adult↗