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Biomedical subjects

L M Zhang

Publications and source records attributed to L M Zhang.

At least 55 records · Page 3Linked to original sources

Correlation between vascular and cellular responses to atrial natriuretic peptide and to sodium nitroprusside.

Atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP) increase cGMP in vascular smooth muscle cells and act as vasodilators in some, but not all, blood vessels. In this present study, we attempted to correlate the ability of these two agents to dilate blood vessels with the ability to increase cGMP in cultured vascular smooth muscle cells. In the isolated guinea pig heart, SNP dose-dependently increased coronary flow while ANP was ineffective. In smooth muscle cells cultured from the coronary system, SNP increased intracellular cGMP in a dose-dependent manner while ANP had no effect on cGMP in these cells. In isolated guinea-pig thoracic aorta, precontracted with K+, both ANP and SNP produced relaxation and ANP was the more potent. In smooth muscle cells cultured from the aorta, ANP and SNP increased cGMP and the potency relationship was similar to the intact vessel. These results support the view that phenotypic properties of vascular smooth muscle cells can account for differences in the response of blood vessels to vasodilators.

Analysis of Variance↗

A study of phlebotomine sandflies (Diptera:Psychodidae) in Yunnan Province. III. Phlebotomus (Adlerius) fengi sp. nov.

Among the phlebotomine specimens collected from Yunnan, China, in 1984, a new species of the subgenus Adlerius Nitzulescu 1931 was identified. The name Phlebotomus fengi is proposed for this species, in memory of the late medical entomologist, Professor Lan Chow Feng. Although generally similar to P. longiductus, P. fengi had distinct pharyngeal armature, style spines, paramere and aedeagus. Phlebotomus fengi may be a vector of visceral leishmaniasis in southern China.

Animals↗

A study of phlebotomine sandflies (Diptera:Psychodidae) in Yunnan Province. V. Phlebotomus (Larroussius) lengi sp. nov.

A new species of the subgenus Larroussius Nitzulescu 1931, named Phlebotomus lengi in honour of the Chinese sandfly taxonomist Professor Yan Jia Leng, was found amongst the phlebotomine sandflies collected in Yunnan Province, China, in 1989. A full description of the male and female of this species is provided. The ascoid formula of P. lengi distinguishes it from all previously described members of the subgenus Larroussius.

Animals↗

Variability of response to atrial natriuretic peptide and sodium nitroprusside in cultured vascular smooth muscle cells from three blood vessels.

OBJECTIVES: Vascular beds vary in their responses to atrial natriuretic peptide and sodium nitroprusside. Both of these agents dilate blood vessels by increasing intracellular guanosine 3',5'-cyclic monophosphate (cyclic-GMP) but activate different enzymes in the vascular smooth muscle cell. We aimed to determine if the response of intracellular cyclic-GMP to atrial natriuretic peptide and sodium nitroprusside varies in smooth muscle cells cultured from different vascular beds. DESIGN: Prospective, repeated measures analysis of concentration-response curves. SETTING: Anesthesia research laboratory of an academic medical center. SUBJECTS: Guinea pigs: Cultured guinea pig smooth muscle cells were obtained from three different blood vessels. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intracellular cyclic-GMP was measured by radioimmunoassay and concentration-response curves of cyclic-GMP to atrial natriuretic peptide and sodium nitroprusside were determined. Cells from the thoracic aorta were the most responsive to atrial natriuretic peptide. Atrial natriuretic peptide (1 microM) increased cyclic-GMP concentrations to 72 +/- 5 pmol/mg (20-fold increase) with a 50% effective concentration of 3 nM. The concentration-response curve in epicardial coronary smooth muscle cells was to the right with an 50% effective concentration for atrial natriuretic peptide of 20 nM and a maximum response of a ten-fold increase in cyclic-GMP. Coronary resistance vessel cells were unresponsive to atrial natriuretic peptide. In response to sodium nitroprusside, the concentration-response curve in coronary resistance vessel cells was significantly to the left of either thoracic aorta cells or the epicardial coronary cells. The 50% effective concentration for sodium nitroprusside in coronary resistance vessel smooth muscle cells was approximately 1 microM, while in both thoracic aortic cells and epicardial coronary cells, the 50% effective concentration was ten times higher. Coronary resistance cells were the most responsive with a 62-fold increase in cyclic-GMP in response to 1 mM of sodium nitroprusside. The maximum response in thoracic aorta cells and epicardial cells was 20- and 30-fold, respectively. CONCLUSIONS: Smooth muscle cells respond differently to vasodilators. The response of these cultured cells mimics the response of the intact vascular bed from which they were obtained. These findings suggest that phenotypic properties of smooth muscle cells within a blood vessel contribute to the responsiveness of the vessel.

Analysis of Variance↗

The effect of pertussis toxin on the growth of vascular smooth muscle cells stimulated by serum or platelet-derived growth factor.

The involvement of a Gi- or G(o)-related G-protein as a regulator of the growth of guinea pig thoracic aorta smooth muscle (TASM) cells was studied by investigating the effects of pertussis toxin (PTX) on the growth of these cells. PTX treatment decreased the growth rate of TASM cells by 70-100%. This effect was apparent within 24 h after exposure to the toxin and persisted for at least 10 days after starting the treatment. The effect of the toxin appeared to be the result of the inactivation of a G-protein because 1) TASM cell membranes contained a 40-kilodalton substrate for the toxin in in vitro assays that was absent in membranes prepared from cells pretreated with toxin; and 2) the effect required both the enzymatic component (A-protomer) of the toxin that inactivates Gi/G(o)-related G-proteins and its B-oligomer necessary for binding and internalization of the A-protomer. The effect of the toxin was not due to an increased level of intracellular cAMP brought about by inactivation of a G-protein that normally inhibits adenylyl cyclase activity. Further, the toxin did not merely make some unknown mitogen rate limiting, because neither increasing concentrations of serum in the growth medium nor supplementation with platelet-derived growth factor could overcome its inhibition of TASM cell growth. Instead, some unknown process regulated by a PTX-sensitive G-protein appears to be required for the normal growth of these cells.

Adenosine Diphosphate Ribose↗

Tolerance to nitroglycerin in vascular smooth muscle cells: recovery and cross-tolerance to sodium nitroprusside.

Treatment with nitric oxide (NO)-producing vasodilators such as nitroglycerin (NTG) and sodium nitroprusside (SNP) causes tolerance. Both NTG and SNP relax blood vessels by increasing guanosine 3',5'-cyclic monophosphate (cGMP) in vascular smooth muscle. We determined the effect of treatment with NTG on cGMP production in cultured pig coronary smooth muscle cells (CSM). Cells incubated for 1 h with 10 microM NTG were desensitized to the effect of NTG on cGMP, but 100 microM NTG was required to induce cross-tolerance to SNP. Acute concentration-response curves of cGMP to NTG and to SNP were determined in cells pretreated for 1 h with 100 microM NTG and compared to response curves in untreated cells. In untreated cells, both NTG and SNP increased cGMP concentration dependently. SNP (1 mM) increased cGMP to 575 +/- 22 pmol/mg vs 55 +/- 4 pmol/mg for 1 mM NTG (P < 0.01, n = 8). Pretreated cells were unresponsive to acutely applied NTG but remained responsive to SNP, although the concentration-response curve to SNP was significantly depressed by approximately 60%. After washout of the NTG pretreatment, the cGMP response to SNP returned to control within 48 h while response to NTG required 72 h. These results show that smooth muscle cells exposed to NTG become tolerant to the effect of NTG on cGMP, and that cross-tolerance to SNP required a 10-fold higher concentration of NTG. The cGMP concentration-response curves of these tolerant cells to rechallenge with NTG or SNP were different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nerve fibers containing dynorphin A in cerebral arteries.

Nerve fibers containing dynorphin (Dyn) A(1-17)-like immunoreactivity were identified around cerebral arteries of guinea pig. The immunoreactive nerve fibers were richly distributed in anterior and middle cerebral arteries, but sparsely in posterior cerebral and basilar arteries. Histofluorescent study showed that large and small cerebral arteries were abundantly innervated by monoamine nerve fibers. Pretreatment with 6-hydroxydopamine or reserpine reduced the concentration of Dyn A in the wall of arteries by about 60% and 30%, respectively. These results demonstrated that there exist Dyn A immunoreactive nerve fibers in cerebral arteries and Dyn A may coexist with monoamine in perivascular nerve fibers.

Animals↗

[Analysis of national maternal death surveillance: 1989-1991].

An analysis of maternal mortality in 247 cities, districts and countries of 30 provinces, municipalities and autonomous regionscovering a population of 100,000,000 in China in 1989-1991 was reported. The total number of live births was 4,201,457 in the pilot area, and the number of maternal deaths was 3,274 giving an average maternal mortality rate (MMR) of 80.0/100,000. After correction, the average MMR was 87.8/100,000. The MMR per annum was in decreasing trends and in different regions were different from one another. The first 6 leading causes of maternal deaths in 3,274 cases, in decreasing order of importance, were: obstetric hemorrhage, pregnancy induced hypertension, cardiac diseases, puerperal infection, amniotic fluid embolism, and hepatic diseases. The result of audit on maternal deaths was as follow: 89.0% of the maternal deaths were avoidable, and 11.0% were unavoidable. Three aspects of the maternal deaths in China were formulated form this study.

Adult↗

[Planned delivery by oxytocin infusion in relation to cephalic dystocia].

To investigate the effect of initiating labor by oxytocin infusion on the outcome of delivery in cephalic presentation, the dystocia rate and final modes of delivery were analyzed in 3,090 cases of head presentation using oxytocin infusion and 2,982 cases with spontaneous onset of labor as control group. The results showed that 562 of the cases using oxytocin developed cephalic dystocia, a rate of 18.2%, while 371(12.4%) of the control group had dystocia. Besides, cephalic dystocia, rates of episiotomy, vacuum extraction and cesarean section were all significantly higher in the oxytocin group than those in the control (P < 0.005). Data also showed that the higher dosage, the more frequency and the longer time of pitocin infusion the higher the rate of dystocia.

Dystocia↗

Blocking effect of rhynchophylline on calcium channels in isolated rat ventricular myocytes.

The effect of rhynchophylline (Rhy) on L-type Ca2+ channel current was studied in rat ventricular myocytes using patch-clamp whole-cell recording technique. When the holding potential was -40 mV, cells were depolarized to 0 mV for 250 ms at frequency of 0.5 Hz, Rhy 10 and 50 mumol.L-1 reduced verapamil-sensitive Ca2+ inward current by 60% and 80%, respectively, without affecting the voltage-dependency of the maximal activation of Ca2+ current. This indicated that the effect of Rhy on the activation of Ca2+ channel was voltage-independent. The effect of Rhy on Ca2+ current reached the maximum at 10 min and was partially recovered by washout of Rhy. A pD2 value of 5.91 and Hill coefficient of 1.1 were obtained from the concentration-response curve.

Alkaloids↗

Effect of rhyncophylline on potassium channels in isolated rat or guinea pig ventricular myocytes.

Effects of rhyncophylline (Rhy) on the voltage-dependent potassium channels in isolated rat and guinea pig ventricular myocytes were studied by using patch clamp whole cell recording techniques. Rhy was found to reduce the steady-state outward current in rat ventricular myocytes when cells were depolarized from holding potential -40 mV to 0 mV. After blocking Ca2+ inward current with CdCl2 0.1 mmol/L, a K+ transient outward current (IA) can be recorded. Rhy 30 mumol/L inhibited the IA 30% when depolarized to +50 mV from the holding potential. The delayed outward (IK) and outward tail current (I(tail)) were also reduced 30% and 60%, respectively by Rhy 30 mumol/L which responded to 4.5 sec long pulse from -40 mV to +50 mV. Whereas, the inward rectifying current (IK1) was not changed by Rhy. The present study suggests that the antiarrhythmic action of Rhy was partially due to the K+ channel blocking effects.

Alkaloids↗

Oligodeoxynucleotides interact with recombinant CD4 at multiple sites.

Phosphodiester oligodeoxynucleotides bearing the 5'-alkylating moiety 4-(N-2-chloroethyl-N-methyl)aminobenzylamine specifically modify recombinant soluble CD4 (rsCD4) in solution. This reaction is saturable with respect to the alkylating oligonucleotide reagent. The existence of at least two binding sites, with different affinities, on the rsCD4 molecule, were demonstrated. The values of apparent Kd for the sites are approximately 0.1 and 1 microM. The existence of two sites was confirmed by electrophoretic analysis of the modified protein, in which two distinct gel bands were seen. The modification is inhibited by excess non-alkylating oligonucleotide, as well as by phosphorothioate oligonucleotides. Quantitative estimates of the competition constants (Kc), for the binding of these competitors of the binding of the alkylating oligonucleotide reagent with rsCD4, have been made. By use of this method, several anionic dyes as well as potential anti-HIV therapeutic agents were also demonstrated to interact with rsCD4. Phosphorothioate oligonucleotides also inhibit binding of rsCD4 with the monoclonal antibody L71.1.1 This monoclonal antibody recognizes the CDR3-like loop (D1 domain) of the rsCD4 molecule. Thus, oligonucleotide binding sites exist on two remote regions (i.e. both the CDR2- and CDR3-like loops) of the D1 domain of CD4.

Alkylating Agents↗

Dynamics of the internalization of phosphodiester oligodeoxynucleotides in HL60 cells.

We have examined the cellular association and internalization of phosphodiester (PO) oligodeoxynucleotides (oligos) with HL60 cells. At 4 degrees C, a 15-mer PO homopolymer of thymidine (FOdT15) exhibits apparent saturation binding (Km = 22 +/- 1 nM) that is competitive with the binding of phosphorothioate (PS) oligos. The value of Kc for SdC28, a PS 28-mer homopolymer of cytidine, is 5 +/- 2 nM. SdC28 was used to strip cell surface fluorescence: Internalized fluorescence accumulated in a (concentration)(time)-dependent fashion, consistent with a pinocytotic mechanism. PS, and to a lesser extent, PO oligos inhibited the rate of internalization of fluorescent albumin, also a marker of pinocytosis. This was correlated with direct in vitro inhibition of protein kinase C (PKC) beta 1 by the PS and PO oligos. Furthermore, other PKC inhibitors (H7, staurosporine, DMSO, PKC pseudosubstrate polypeptide) also inhibited intracellular accumulation of pinocytosed materials, perhaps by stimulating the exocytosis rate. In HL60 cells, the pinocytotic internalization of charged oligos appears to be dependent on intact PKC kinase activity, which is inhibited in vitro by PS and PO oligos.

Amino Acid Sequence↗

Modification of antisense phosphodiester oligodeoxynucleotides by a 5' cholesteryl moiety increases cellular association and improves efficacy.

Phosphodiester oligodeoxynucleotides bearing a 5' cholesteryl (chol) modification bind to low density lipoprotein (LDL), apparently by partitioning the chol-modified oligonucleotides into the lipid layer. Both HL60 cells and primary mouse spleen T and B cells incubated with fluorescently labeled chol-modified oligonucleotide showed substantially increased cellular association by flow cytometry and increased internalization by confocal microscopy compared to an identical molecule not bearing the chol group. Cellular internalization of chol-modified oligonucleotide occurred at least partially through the LDL receptor; it was increased in mouse spleen cells by cell culture in lipoprotein-deficient medium and/or lovastatin, and it was decreased by culture in high serum medium. To determine whether chol-modified oligonucleotides are more potent antisense agents, we titered antisense unmodified phosphodiester and chol-modified oligonucleotides targeted against a mouse immunosuppressive protein. Murine spleen cells cultured with 20 microM phosphodiester antisense oligonucleotides had a 2-fold increase in RNA synthesis, indicating the expected lymphocyte activation. Antisense chol-modified oligonucleotides showed an 8-fold increase in relative potency: they caused a 2-fold increase in RNA synthesis at just 2.5 microM. The increased efficacy was blocked by heparin and was further increased by cell culture in 1% (vs. 10%) fetal bovine serum, suggesting that the effect may, at least in part, be mediated via the LDL receptor. Antisense chol-modified oligonucleotides are sequence specific and have increased potency as compared to unmodified oligonucleotides.

Animals↗

Check list and geographical distribution of phlebotomine sandflies in China.

A total of 42 species of sandflies, included in five genera, have been recorded from 31 of 32 provinces, municipalities and autonomous regions of China (excluding Heilongjiang Province). Five species, namely Phlebotomus alexandri, P. chinensis, P. longiductus, P. sichuanensis and P. smirnovi (syn. P. wui), are known to be vectors of human leishmaniasis. A list of these 42 phlebotomines is given, and their geographical distributions in China are described.

Animals↗

Regulation of atrial natriuretic peptide receptors in vascular smooth muscle cells: role of cGMP.

We tested the hypothesis that intracellular guanosine 3',5'-cyclic monophosphate (cGMP) regulates atrial natriuretic peptide (ANP) receptors. The effect of chronic exposure to ANP, sodium nitroprusside (SNP), and 8-bromo-cGMP (8-BrcGMP) on ANP receptors and cGMP formation was determined in guinea pig thoracic aorta smooth muscle cells (TASM) and in coronary artery smooth muscle cells (CASM). TASM express both the ANP-activated guanylyl cyclase (B-receptor) and the clearance receptor (C-receptor) and respond to ANP with increased cGMP. CASM exhibit only the ANP C-receptor. In TASM, 24-h treatment with 1 microM atriopeptin (AP) III [rat ANP-(103-126)] caused a sixfold increase in basal cGMP levels, which were unaltered in CASM. In AP III-treated TASM, maximal binding of 125I-labeled AP III (Bmax) was reduced 40% while affinity [dissociation constant (KD)] was unaltered. In CASM, Bmax and KD were not affected. In treated TASM, washed free of AP III, acute dose-response curves of cGMP to AP III were not different from that in untreated cells. In both TASM and CASM, basal cGMP levels were elevated and Bmax was decreased by 6-h treatment with SNP. SNP did not alter the acute response of cGMP to AP III. In both cell types, 8-BrcGMP for 6 h caused reduction in Bmax. These findings support the conclusion that elevated cGMP was necessary for ANP-induced downregulation of receptors. The unaltered responsiveness of cGMP to AP III suggests the B-receptor was not altered and the reduced Bmax was due to decreased C-receptor.

8-Bromo Cyclic Adenosine Monophosphate↗

Tolerance to sodium nitroprusside. Studies in cultured porcine vascular smooth muscle cells.

BACKGROUND: Tolerance to nitrovasodilators, including sodium nitroprusside (SNP), is a clinical problem. SNP causes vasodilatation by releasing nitric oxide, which stimulates intracellular guanosine 3':5'-cyclic monophosphate (cGMP) accumulation in smooth muscle cells. This study examined tolerance to SNP in coronary smooth muscle cells by measuring intracellular cGMP formation. METHODS: Smooth muscle cells were isolated from pig coronary vessels. Intracellular cGMP formation in response to SNP, nitroglycerine, and atrial natriuretic peptide (ANP) was quantitated by radioimmunoassay before and after chronic pretreatment. RESULTS: The detection of tolerance of cells rechallenged with SNP required exposure to a minimum concentration of 1 microM for SNP for at least 60 min. In untreated cells, acutely applied 100 microM SNP increased the cGMP concentration to 300 +/- 8.6 pmol/mg protein (mean +/- SEM). The cGMP concentration in cells pretreated with 1 microM SNP for 60 min increased to 213 +/- 11 pmol/mg in response to 100 microM SNP (P < 0.01, compared to untreated cells). The pretreatment of cells for 60 min with increasing concentrations of SNP caused a sequential reduction in the acute concentration-response curves of cGMP to SNP. After a 6 h washout period, cGMP accumulation in response to a rechallenge with SNP returned to control levels. The acute concentration-response curve of cGMP to SNP in cells pretreated with 100 microM nitroglycerine for 60 min was reduced significantly. Pretreatment with 100 microM SNP for 60 min did not change the response of cAMP accumulation to isoproterenol or forskolin. However, the response of cGMP formation to ANP was potentiated after pretreatment. In addition, elevation of basal cAMP or cGMP concentrations, induced with isoproterenol or ANP, respectively, did not alter the response of cGMP formation to SNP. CONCLUSION: The study yielded the following findings: (1) reversible tolerance to SNP was induced in cultured vascular smooth muscle cells; (2) chronic exposure to nitroglycerine induced cross-tolerance to SNP; (3) cells that were tolerant to SNP showed a potentiated response to ANP.

Animals↗