Search PubMed⌕ Search

Biomedical subjects

Y H Ma

Publications and source records attributed to Y H Ma.

At least 55 records · Page 3Linked to original sources
PubMed1991

Inhibitors of cytochrome P-450 attenuate the myogenic response of dog renal arcuate arteries.

The role of cytochrome P-450 in the myogenic response of isolated, perfused renal arcuate arteries of dogs to elevations in transmural pressure was examined. The phospholipase A2 inhibitor oleyloxyethylphosphorylcholine (1 and 10 microM) inhibited the greater than threefold increase in active wall tension in these arteries after an elevation in perfusion pressure from 80 to 160 mm Hg. Inhibition of cyclooxygenase activity with indomethacin (1 or 10 microM) had no effect on this response. The cytochrome P-450 inhibitors ketoconazole (10 and 100 microM) and beta-diethyl-aminoethyldiphenylpropylacetate (SKF 525A, 10 and 100 microM) also inhibited the myogenic response. At a pressure of 160 mm Hg, SKF 525A (10 microM) and ketoconazole (100 microM) reduced active wall tension in renal arteries by approximately 70%. Partial inhibition of the myogenic response was obtained after perfusion of the vessels with mechanism-based inhibitors of P-450, 1-aminobenzotriazole (75 microM) and 12-hydroxy-16-heptadecynoic acid (20 microM). The thromboxane receptor antagonist SQ 29,548 (1 or 10 microM) had no effect on the pressure-induced increase in active wall tension in renal arteries. Arachidonic acid (50 microM) constricted isolated perfused renal arteries and potentiated the myogenic response in the presence of indomethacin. This response was completely reversed by ketoconazole (100 microM) or SKF 525A (100 microM). Microsomes (1 mg/ml) prepared from small renal arteries (200-500 microns) and incubated with [1-14C]arachidonic acid (0.5 mu Ci, 50 microM) produced a metabolite that coeluted with 20-hydroxyeicosatetraenoic acid (20-HETE) during reversed-phase high-performance liquid chromatography. The formation of this product was inhibited by both ketoconazole and SKF 525A at concentrations of 10 and 100 microM. These results are consistent with the involvement of the vasoconstrictor 20-HETE and other cytochrome P-450 metabolites of endogenous fatty acids in the myogenic response.

Animals↗
PubMed1991

The role of Ca(2+)-related events in glucose-stimulated desensitization of insulin secretion.

The spontaneous decline of insulin secretion (third phase) that occurs under a variety of secretory conditions is well documented and suggests a general impairment or desensitization of the secretory process. We have examined several aspects of Ca2+ flux as well as regulators of Ca-linked second messenger events in freshly isolated rat islets chronically stimulated with glucose over 24 h, a period that encompasses initial (hour 1), peak (hour 3), and subsequent impaired or desensitized (hour 20-22) secretion. In islets incubated for these periods in HB104 medium with 22 mM glucose, 45Ca2+ uptake did not vary (12.6 +/- 1.6 vs. 10.2 +/- 1.7 vs. 13.2 +/- 3.4 pmol Ca2+/islet.10 min at 1, 3, and 22 h, respectively). Chronic incubation in 2 mM glucose reduced total Ca2+ uptake at each of the time periods, but, again, uptake did not change with desensitization (9.8 +/- 1.4 vs. 6.6 +/- 2.1 vs. 7.8 +/- 2.3 pmol Ca2+/islet.10 min). In 11 mM glucose, the Ca channel antagonist verapamil (1-10 microM) reduced insulin secretion by 55-80% in a dose-dependent manner over 1-3 h; islets continuously exposed to verapamil escaped inhibition by 20 h even at the highest concentration. However, in islets first exposed to 10 microM verapamil only during 20-22 h, hourly insulin secretion was suppressed 25%, 45%, and 33% at 20, 21, and 22 h, respectively, indicating that glucose-desensitized islets were still sensitive to further inhibition of Ca channels. Staurosporine (1 microM), an inhibitor of protein kinase-C activity, progressively inhibited glucose-stimulated insulin secretion from 48% at 1 h to more than 80% by 3 h; again, this inhibitory effect was lost by 20 h of chronic staurosporine. When staurosporine was first administered at 20 h, insulin secretion was modestly suppressed and returned to control values in the next hour. With continuous glucose, the islet response to positive stimulation of endogenous C-kinase activity by carbachol was maintained. The Ca/calmodulin inhibitor trifluoroperazine also inhibited insulin secretion by 75-80% during 1-3 h and continued to exert inhibitory effects through 23 h of continuous administration. We conclude that even though insulin secretion has desensitized to glucose, 1) Ca2+ entry is unchanged and is still regulated by glucose, 2) voltage-dependent Ca channels are still sensitive to blockade by acute verapamil, but can desensitize to chronic verapamil; 3) stimulus-enhanced C-kinase activity may be especially labile during glucose-induced desensitization, while 4) possible Ca/calmodulin potentiation of secretion persists through the three secretory phases.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkaloids↗
PubMed1991

[A study of the inheritance and linkage of resistance to four strains of soybean mosaic virus in soybeans].

Ten susceptible x resistant and resistant x resistant crosses were made among eight varieties, of which seven were previously identified as resistant to one to four SMV strains, in order to investigate the inheritance of resistance to the four strains (Sa, Sc, Sg, and Sh) and the linkage relationship among the resistant genes. Seeds from F2 individual plants were randomly divided and planted in two separated nurseries, in which the seedlings were inoculated with two different strains. The genotype of each F2 plant was detected from the reaction of its F3 progenies to the two strains. The results showed that the resistance to each of the four strains was conditioned by a dominant gene which was labelled here with Ra, Rc, Rg, and Rh, respectively. All the four loci appeared to be in a same linkage group with the order of Rg--Rh--Ra--Rc. The recombination value between Ra and Rc was estimated to be 25.4 +/- 7.7%, and those between Rg and Rh, Ra and Rh, Ra and Rg, and Rc and Rg to be 27.3 +/- 5.4%, 23.5 +/- 5.2%, 41.1 +/- 8.5%, and 46.5 +/- 7.5%, respectively. The genes resistance to Sa in Kwanggyo and "7222" were determined at the same locus, so were the resistant genes for Sc. In addition, this linkage group seemed to be not related with the first and eighth linkage group.

Crosses, Genetic↗
PubMed1990

Postunclipping renal blood flow in one-kidney, one-clip hypertensive rats.

Removal of the arterial clip (unclipping) in one-kidney, one-clip (1K, 1C) Goldblatt hypertensive rats causes rapid return of mean arterial pressure (MAP) to normotensive levels. An extracorporeal circulation was established between the renal and jugular veins to evaluate the influence of unclipping on renal blood flow (RBF) in Inactin-anesthetized 1K, 1C rats. MAP in rats with the extracorporeal circulation was 182 +/- 5 mmHg before unclipping or sham operation. MAP decreased to 113 +/- 4 mmHg within 2 h after unclipping compared with 169 +/- 13 mmHg in sham-unclipped rats. RBF increased by 2.8 ml.min-1.g-1 from a basal level of 3.8 +/- 0.3 after unclipping and was maintained approximately 40% above the basal level for 2 h, although renal vascular resistance was 94% greater than in uninephrectomized control rats. Heart rate did not change in either unclipped or sham-operated rats. Indomethacin (7 mg/kg) did not affect unclipping-induced changes in MAP, RBF, or urine output; however heart rate decreased immediately after unclipping and remained approximately 25-35 beats/min below control levels for the 2-h observation period. In rats lacking the extracorporeal circuit, MAP decreased (P less than 0.005) and heart rate increased (P less than 0.05) in response to unclipping. Nevertheless, unclipping-induced tachycardia was significantly less than that caused by nitroprusside infusions causing similar decrements in MAP. The results suggest that the sustained increment in RBF after unclipping in chronic, established 1K, 1C hypertension may be associated with postunclipping hypotension and diuresis, that blockade of prostaglandin synthesis may unmask unclipping-induced bradycardia, and that prostaglandins are not essential for postunclipping changes in renal hemodynamics.

Animals↗
PubMed1990

Effect of glucagon or somatostatin on desensitized insulin secretion.

In this study we have examined the role of glucagon and somatostatin in regulating glucose-induced desensitization of insulin secretion from rat islets. Measured in batch incubations with medium routinely used to induce three phases of insulin secretion, secreted glucagon levels fell off over 24 h to 20% of peak secretion levels. Although more responsive to various secretagogues, somatostatin secretion also declined to the same degree. Thus, the A- and D-cells desensitize to chronic stimulation as does the B cell. In other experiments, added glucagon (10(-6) M) enhanced glucose (11 X 10(-3) M)-stimulated insulin secretion 34% in the first 3 h; however, islets became insensitive to continuous glucagon by 4 h. The exogenous glucagon did not prevent or delay glucose-induced desensitization of insulin secretion. When glucagon was administered as acute 1-h tests over continuous glucose administration, the degree of B-cell response did not differ in the 1st, 3rd, or 6th hours and appeared to increase in the 21st hour. When islets were perifused continuously with glucose (22 X 10(-3) M) plus 3 X 10(-7) M somatostatin, glucose-induced insulin secretion was suppressed 50% in the first 3 h, but this inhibitory effect disappeared after 6 h. Desensitization was slightly delayed, but not prevented. When somatostatin was administered as acute 1-h tests over continuous glucose perifusion, the B-cell response was relatively constant in the 3rd, 6th, and 21st hours. Results show that 1) islet release of glucagon and somatostatin desensitizes during constant stimulation; and 2) islet release of insulin desensitizes to chronic potentiation or inhibition, respectively, by these hormones. Furthermore, 3) changing B-cell sensitivity to either glucagon or somatostatin cannot account for observed desensitization of insulin secretion with chronic glucose exposure.

Animals↗
PubMed1989

Identification of a second "French Canadian" LDL receptor gene deletion and development of a rapid method to detect both deletions.

Hobbs et al. (N. Engl. J. Med. 317: 734-737, 1987) reported a large deletion of approximately 10 kilobases in the 5' portion of the human low-density lipoprotein (LDL) receptor gene. This deletion affects about 60% of familial hypercholesterolemia (FH) heterozygotes in the French Canadian population. We have developed a rapid, convenient method for the detection of the deletion using double digestion with the restriction enzymes XbaI and EcoRV, or triple digestion with XbaI, EcoRV and XmnI, and a 650 bp cDNA probe, radio-labeled using a random oligonucleotide primer technique. Eighty French Canadian FH heterozygotes were screened for the presence of the deletion. Forty-seven (59%) of them were found to carry the 10 kb deletion. Using the same method, we also identified a new mutation which was found in four of the 80 (5%) FH patients. This mutation has been found to be a 5 kb deletion removing exons 2 and 3 of the LDL receptor gene, which correspond to the first two repeats of the LDL receptor binding domain. Cosegregation of the 5 kb deletion and the FH phenotype was observed in one family. Possible structure-function relationship is discussed.

Canada↗
PubMed1988

Antagonism of the vasodilator effects of a platelet activating factor precursor in anesthetized spontaneously hypertensive rats.

The hemodynamic effects of platelet activating factor (PAF), PAF antagonists and a precursor of PAF, 1-palmityl-2-acetyl-glycerol (PAG), were examined in pentobarbital-anesthetized spontaneously hypertensive rats to determine whether functionally significant amounts of PAF are produced via the cholinephosphotransferase pathway of PAF synthesis in vivo. Intravenous bolus doses of PAF, PAG and nitroprusside elicited hypotension and active mesenteric vasodilatation. Responses to PAG were slower in onset and longer in duration than those of PAF and nitroprusside. The specific PAF antagonists, CV-3988 and SRI 63-675, attenuated PAG- and PAF-, but not nitroprusside-induced changes in blood pressure and mesenteric flow/resistance. In contrast, captopril, which blocked the effects of angiotensin I, did not influence the hypotension caused by PAG, PAF and nitroprusside. The results suggest that the vasodilator effects of PAG are attributable to PAF produced from this alkylacetylglycerol, and the renin-angiotensin system does not appear to influence the biotransformation of PAG to PAF or the hypotensive action of PAF.

Animals↗
PubMed1988

Insect-derived crude drugs in the Chinese Song dynasty.

Fifty-four kinds of crude drug derived from insects are listed in the "herbal" Jing-shi-zheng-lei-da-guang-ben-cao (1108 A.D.) edited during the Chinese Song dynasty (960-1280 A.D.). We considered each of them from the viewpoint of various herbals and have commented on them, the order being adhered to in most cases. We added our own findings of identification of insect crude drugs available on the market. The crude drugs emphasized are mantis egg case, wasp's nest, scarab larva, red cicada, snipe fly, horse fly, flying cockroach, Eupolyphaga, Chinese Cantharides and scarab beetle. Others are discussed to a lesser extent.

Animals↗
PubMed1986

Human apolipoprotein B: chromosomal mapping and DNA polymorphisms of hepatic and intestinal species.

Apolipoprotein B (apoB) is the major protein component of low-density and very-low-density lipoproteins. We have recently isolated nonoverlapping cDNA clones for apoB and confirmed their identity by sequence comparisons. We now report the mapping of the human apoB gene (APOB) to the p23-p24 region of chromosome 2 by examination of human-mouse somatic cell hybrids and by in situ hybridization to human chromosomes. Thus, APOB is unlinked to members of the dispersed gene family encoding other apolipoprotein species or to the gene encoding the low-density lipoprotein receptor. Hybridization analysis with genomic DNA and liver and intestinal mRNA suggests that APOB encodes both the high-molecular-weight form of apoB (apoB100) incorporated into very-low-density lipoproteins in liver and the lower-molecular-weight form (apoB48) incorporated into chylomicrons in intestine. Restriction fragment length polymorphisms of APOB have been identified and should prove useful in examining the possibility that genetic variations of APOB are involved in dyslipoproteinemias and atherosclerosis.

Apolipoproteins B↗
PubMed1985

Human apolipoprotein B: identification of cDNA clones and characterization of mRNA.

Apolipoprotein B (apoB) is a major protein component of low density and very low density lipoproteins. Because of its large size and heterogeneity, molecular studies of apoB have been difficult, and its structure and regulation remain poorly understood. We now report the identification of human apoB cDNA clones by antibody screening of hepatoma libraries in the expression vector lambda gt11. Both oligo(dT) primed and random primed libraries were constructed and screened with polyclonal antibodies to intact apoB, as well as with antibodies raised against a synthetic peptide based on the limited amino acid sequence available for apoB. The identity of the clones was unambiguously established by comparisons of the cloned cDNA sequences with apoB amino acid sequences. The clones hybridize to an exceptionally large 20 kb mRNA that is present in liver and intestine but not other tissues examined, consistent with the distribution expected from protein biosynthetic studies. The properties of the mRNA have implications for the biogenesis of the multiple apoB molecular weight forms secreted by liver and intestine.

Apolipoproteins B↗
PubMed1985

Action mechanism of the platelet aggregation inducer and inhibitor from Echis carinatus snake venom.

Platelet aggregation inducer and inhibitor were isolated from Echis carinatus snake venom. The venom inducer caused aggregation of washed rabbit platelets which could be inhibited completely by heparin or hirudin. The venom inducer also inhibited both the reversibility of platelet aggregation induced by ADP and the disaggregating effect of prostaglandin E1 on the aggregation induced by collagen in the presence of A23187, arachidonate, ADP and platelet-activating factor (PAF) with an IC50 of around 10 micrograms/ml. It did not inhibit the agglutination of formaldehyde-treated platelets induced by polylysine. In the presence of indomethacin or in ADP-refractory platelets or thrombin-degranulated platelets, the venom inhibitor further inhibited the collagen-induced aggregation. Fibrinogen antagonized competitively the inhibitory action of the venom inhibitor in collagen-induced aggregation. In chymotrypsin-treated platelets, the venom inhibitor abolished the aggregation induced by fibrinogen. It was concluded that the venom inducer caused platelet aggregation indirectly by the conversion of prothrombin to thrombin, while the venom inhibitor inhibited platelet aggregation by interfering with the interaction between fibrinogen and platelets.

Adenosine Diphosphate↗
PubMed1985

Characterization of the platelet aggregation inducer and inhibitor from Echis carinatus snake venom.

Echis carinatus venom was separated into twenty fractions by means of ultrafiltration and CM-Sephadex C-50 column chromatography. Fraction II possessed inhibitory activity on the aggregation of washed rabbit platelets and fraction XII possessed the procoagulant and platelet aggregation-inducing activity. Both were further purified by gel filtration on a Sephacryl S-200 column. The purified aggregation inducer was a glycoprotein with procoagulant activity 10-12-times that of the crude venom. It possessed proteinase and amidase but was devoid of esterase activity. The molecular weight was 16 000, and it contained 8.7% of neutral sugar. The isoelectric point was pH 7.6. The purified aggregation inhibitor was a single peptide chain with a molecular weight of 6800 and contained 22.1% of neutral sugar. The isoelectric point was pH 4.8. It was devoid of any enzymatic activity of the crude venom. The IC50 was about 10 micrograms/ml on the thrombin-induced platelet aggregation. The inhibitory activity was fully retained after the treatment of the venom aggregation inhibitor with neuraminidase, but was completely destroyed by sodium metaperiodate. Upon heat treatment at 90 degrees C, the venom aggregation inhibitor was heat stable at pH 5.5 for 4 h, but was completely destroyed after 2 h at pH 8.9 and retained about 50% of its inhibitory activity of the control at pH 7.2 for 4 h. The venom aggregation inhibitor decreased the elasticity of the whole blood clot, and this effect was related to its inhibitory action on platelet aggregation instead of blood coagulation.

Amino Acids↗
PubMed1977

Modification of hydroxyindole-O-methyltransferase activity in experimental pineocytomas induced in hamsters by a human papovavirus (JC).

Hydroxyindole-O-methyltransferase (HIOMT) (HIOMT) activity was studied and compared in 7 pineal tumors (pineocytomas) induced in vivo in Syrian hamsters after postnatal inoculation with strains of human papovavirus (JC). Levels of tumor HIOMT activity were correlated with degree of cytologic differentiation of the pineocytes of each neoplasm, as judged from electrom micrographs. The relative capacities of the HIOMT in the tumors to methylate three related substrates gave similar ratios in the individual tumors and were not different from those of HIOMT in normal hamster pineal glands.

Acetylserotonin O-Methyltransferase↗
PubMedDate not supplied

Role of cytochrome P-450 in elevating renal vascular tone in spontaneously hypertensive rats.

The contribution of cytochrome P-450 metabolites of arachidonic acid in elevating vascular tone in the kidneys of adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was examined using a juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. At 80 mm Hg, the basal internal diameters of arcuate and interlobular arteries and proximal and distal afferent arterioles of the SHR averaged 341 +/- 15.81 +/- 5.24 +/- 0.5 and 19 +/- 0.3 micron, respectively. These diameters were 5-29% smaller (p < 0.05) than those measured in corresponding vessels in WKY rats. Addition of the P-450 inhibitors, ketoconazole (100 microM) or 17-octadecynoic acid (17-ODYA, 20 microM), to the perfusate and bath increased the diameters of the preglomerular vasculature of the SHR by 6-29%, but by only 3-13% in WKY rats and reduced significantly the differences in pressure-diameter relations between the two groups. The rate of formation of 20-hydroxyeicosatetraenoic acid (20-HETE) by renal cortical microsomes was similar in SHR and WKY rats. However, the production of epoxyeicosatrienoic acids (EETs) by cortical microsomes was 87% lower and dihydroxyeicosatrienoic acids (DHETs) 70% higher in the SHR than WKY rats. Ketoconazole (100 microM) reduced the formation of 20-HETE by 80%, and EETs and DHETs production by more than 98% in SHR and WKY rats. 17-ODYA (20 microM) reduced the formation of 20-HETE, EETs and DHETs by more than 98% in both groups. These results suggest that cytochrome P-450 metabolites of arachidonic acid contribute to the elevated renal vascular tone in adult SHR. This may be due to an enhanced vascular responsiveness to vasoconstrictor P-450 metabolites in SHR or an elevated local production of vasoconstrictor eicosanoids in the renal vasculature of SHR rather than in renal cortical tissue.

Animals↗
PubMedDate not supplied

Two DNA restriction fragment length polymorphisms associated with Ag(t/z) and Ag(g/c) antigenic sites of human apolipoprotein B.

Several high frequency restriction fragment length polymorphisms (RFLPs) associated with the human gene for apolipoprotein B have been previously reported by Priestly et al. The EcoRI RFLP here was shown to be very strongly associated with the Ag(t/z) immunochemical polymorphism of human low density lipoproteins, allowing correct Ag(t/z) phenotyping of 17 (out of 17 tested) unrelated individuals. The Xbal RFLP was associated with the Ag(g/c) immunochemical polymorphism, permitting correct phenotyping of 14 (out of 17 tested) unrelated individuals. Its close association with an RFLP permitted localization of the Ag(t/z) polymorphism to the C-terminal end of the apolipoprotein B peptide, and allowed detailed discussion of its probable molecular basis.

Apolipoproteins B↗
PubMedDate not supplied

Apolipoprotein B: the Ag(a1/d) immunogenetic polymorphism coincides with a T-to-C substitution at nucleotide 1981, creating an Alu I restriction site.

Short cDNA fragments covering the entire coding region for apolipoprotein (apo) B have been cloned in the pING expression vector. A monoclonal antibody specific for the Ag(d) epitope on apo B has been used, together with the expressed apo B peptides, to locate this epitope to a stretch of 26 amino acids. Sequencing of this region from several genomic DNAs of known Ag(a1/d) genotype showed a single T-to-C substitution at nucleotide 1981, creating an Alu I restriction site and resulting in a val to ala residue change in the corresponding peptide (at position 591 in the mature protein). Southern blots, using the Alu I restriction endonuclease and a short probe for this region of the cDNA, showed perfect correspondence between the restriction fragment length polymorphism and the Ag(a1/d) immunochemical polymorphism in all 17 persons examined.

Apolipoproteins B↗
PubMedDate not supplied

Apolipoprotein B gene haplotypes. Association between Ag and DNA polymorphisms.

Berg et al. (Clin Genet 1986;30:515-520) have reported that an Xba I DNA polymorphic site in exon 26 of the apolipoprotein (apo) B gene is associated both with the Ag(x/y) immunochemical polymorphism and with elevated serum lipoprotein levels. Ma et al. (Arteriosclerosis 1987;7:301-305) have reported that the same Xba I polymorphism is associated with a different immunochemical polymorphism, Ag(c/g). To extend and clarify these observations, we have determined the Ag and Xba I polymorphism for 106 individuals. We find that the Xba I restriction fragment length polymorphism is in linkage disequilibrium with both Ag(x/y) and Ag(c/g) loci; thus, all 31 Xba I(X1/X1) genotypes observed in this study are also Ag(y/y). All but one of 22 Xba I(X2/X2) genotypes are also Ag(g/g). For individuals homozygous at either two or three of these loci, it was possible to determine the haplotypes for 128 apo B alleles. Of the eight possible apo B haplotypes, only four were represented in this unambiguous subpopulation, although other minor haplotypes were present in the total population from which it was derived. The identification of major apo B haplotypes in human populations may simplify the search for significant correlations between certain apo B alleles and lipid levels and atherosclerosis.

Apolipoproteins B↗