Biomedical subjects
Publications and source records attributed to R Chen.
Zhigancao injection can antagonise the arrhythmia induced by chloroform, adrenaline, aconitine, strophanthine K and barium chloride, slow the heart rate, prolong P-R and Q-T intervals and antagonise the positive chronotropic response induced by isoprenaline. The LD50 of zhigancao injection is 41.2g/kg in nice by intraperitoneal.
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MK-801, a non-competitive antagonist of N-methyl-D-aspartate-type glutamate receptors, was tested for its ability to antagonize excitotoxic actions of N-methyl-D-aspartate or quisqualic acid injected into the brains of seven-day-old rats. Stereotaxic injection of N-methyl-D-aspartate (25 nmol/0.5 microliters) or quisqualic acid (100 nmol/1.0 microliter) into the corpus striatum under ether anesthesia consistently produced severe unilateral neuronal necrosis in the basal ganglia, dorsal hippocampus and overlying neocortex. The distribution of the damage corresponded to the topography of glutamate receptors in the vulnerable regions demonstrated by previous autoradiographic studies. N-Methyl-D-aspartate produced severe, confluent neuronal destruction while quisqualic acid typically caused more selective neuronal necrosis. Intraperitoneal administration of MK-801 (0.1-1.0 mg/kg) 30 min before N-methyl-D-aspartate injection had a prominent dose-dependent neuroprotective effects as assessed morphometrically by comparison of bilateral striatal, hippocampal and cerebral hemisphere cross-sectional areas five days later. A 1 mg/kg dose of MK-801 given as pre-treatment completely protected the infant brain. The same dose of MK-801 was also completely protective when administered 30 or 40 min after N-methyl-D-aspartate and afforded partial protection when given 2 h later. MK-801 pre-treatment also prevented the electrically confirmed behavioral seizures induced by N-methyl-D-aspartate. The drug significantly reduced striatal but not hippocampal or neocortical injury when given as two doses (1 mg/kg) 30 min prior to and immediately following quisqualic acid injection. The data indicate that systemic administration of MK-801 can prevent N-methyl-D-aspartate-induced neuronal injury in perinatal rat brain even when administered after the initial insult. MK-801 also partially antagonized quisqualic acid-mediated neurotoxicity, suggesting that quisqualic acid-induced toxicity is, in part, mediated through N-methyl-D-aspartate receptor activation. The sensitivity of the developing brain to the toxicity of N-methyl-D-aspartate provides a sensitive and reproducible in vivo model for exploring these issues and for screening prospective neuroprotective drugs that act at the N-methyl-D-aspartate receptor-channel complex.
The effect of aerobic perfusion, of up to 90 min global ischemia, and of reperfusion on 125I-labeled porcine endothelin (125I-ET-1) binding site density (Bmax), affinity (KD), and selectivity was investigated using cardiac membranes harvested from adult Sprague-Dawley rats. Membranes from nonperfused hearts bound 125I-ET-1 with a Bmax of 117.0 +/- 8.8 fmol/mg protein, a KD of 0.076 +/- 0.005 nM, and a Hill coefficient approaching unity. Neither aerobic perfusion nor 10 min of normothermic ischemia and subsequent reperfusion altered these binding parameters. The extension of the ischemic episode increased Bmax (23, 32, 62, and 60% increase after 20, 30, 60, and 90 min ischemia, respectively). Reperfusion further increased Bmax (P less than 0.01 at 15 min reperfusion after 20 and 30 min ischemia, and after 30 min reperfusion following 60 min ischemia) without changing selectivity. Affinity was reduced after 60 (P less than 0.05) and 90 (P less than 0.01) min ischemia. Ischemia at 22 degrees C had no effect on the density or affinity of these binding sites.
We observed HLA associations in patients with nasopharyngeal carcinoma from northern China. There was an increased risk of nasopharyngeal carcinoma associated with HLA-B35 and a difference in the HLA association between patients with early- and late-onset disease. The frequency of B35 was significantly higher in patients than in control subjects, especially in early-onset patients (less than 30 years old). Late-onset patients had a higher frequency of DR2 as compared with normal subjects.
The oncogenes most frequently detected in human tumors belong to the ras gene family (Ha-ras, Ki-ras, and N-ras). These genes encode a group of closely related 21,000 dalton proteins termed p21. An immunohistochemical study of ras p21 expression was carried out on paraffin sections of 54 human breast carcinomas using monoclonal antibodies to p21. The control group consisted of ten cases of benign fibrocystic disease. The p21 expression was significantly higher in cancer cells than in epithelial cells of control specimens. No correlations, however, were observed between oncogene product expression and tumor size, histologic type, or grade. As a group, tumors with axillary lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors. However, because of the significant overlap in individual p21 values, it is unlikely that the immunohistochemical assay for p21 could be used to predict the behavior of mammary carcinomas.
The structures of various covalent phosphorylated derivatives of alpha-chymotrypsin (alpha-CT) have been studied by 31P NMR spectroscopy. Diisopropylphosphoryl-alpha-chymotrypsin (alpha-DIPCT) shows a single 31P signal at ca. 0.0 ppm (pH 4). At low pH, the 31P NMR spectrum of alpha-DIPCT gradually changed with the appearance of one or two additional peaks. The ratio of the peaks varied with pH, time, and concentration. One of these two new downfield peaks (both at ca. 2.0 ppm) has been previously identified by Markley and co-workers (Markley, 1979; Porubcan et al., 1979) and van der Drift et al. (1985) as an aged monoisopropylphosphoryl-alpha-chymotrypsin (alpha-MIPCT) and is confirmed by our studies. A new additional downfield signal, separate from the alpha-MIPCT signal, is attributed to a dimer of the phosphorylated alpha-DIPCT. Phosphorylation of the enzyme with diphenyl chlorophosphate yields a monophenylphosphoryl-alpha-chymotrypsin (alpha-MPPCT) that also showed a single 31P signal at -2.1 ppm (pH 7). However, the spectrum did not change as a function of pH, incubation time, or concentration. Comparison of the 31P chemical shifts of the native and denatured phosphorylated derivatives of alpha-chymotrypsin suggests changes in the conformation about the P-O ester bonds are at least partially responsible for the various 31P chemical shift differences.
L-657,743 (MK-912), a highly potent and selective alpha 2-adrenoceptor antagonist was tritiated to a high specific activity and its binding characteristics to brain tissue were determined. The specific binding of [3H]L-657,743 to rat cerebrocortex was saturable, reversible, and dependent on tissue concentration. In saturation studies, [3H]L-657,743 binding was resolved into two high affinity components exhibiting Kd values of 86 pM and 830 pM with densities of 82 fmol/mg protein and 660 fmol/mg protein, respectively. Based on the binding potencies of a variety of compounds with differing receptor selectivities, the sites labeled by [3H]L-657,743 were characteristic of alpha 2-adrenoceptors. In contrast to alpha 2-antagonists, alpha 2-agonists displayed shallow competition curves. In the presence of 100 microM GTP, Gpp(NH)p or 150 mM NaCl, the competition curve for epinephrine was shifted to the right, whereas that for yohimbine was unaffected. In studies utilizing human cerebrocortical tissue, [3H]L-657,743 also bound with high affinity to sites characteristic of alpha 2-adrenoceptors.
[3H]L-365,260, [(3R-(+)-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-N'-(3-methylphenyl)urea], a new potent and selective nonpeptide brain cholecystokinin (CCK-B) and gastrin receptor antagonist, bound saturably and reversibly to guinea pig brain membranes. Scatchard analysis indicated a single class of high affinity (Kd = 2.3 nM) binding sites. The binding of [3H]L-365,260 was stereospecific, because unlabeled L-365,260 (an R-enantiomer) was approximately 100 times more potent than its S-enantiomer in displacing binding. The relative potencies of various CCK/gastrin-related peptides and nonpeptide peripheral CCK-A antagonists in displacing [3H]L-365,260 brain binding correlated with their potencies in displacing the binding of 125I-CCK to brain receptors but not their potencies in displacing the peripherally selective CCK-A ligand [3H]L-364,718 from pancreatic receptors. The regional distribution of [3H]L-365,260 binding in various brain areas correlated with 125I-CCK binding. Specific [3H]L-365,260 binding to guinea pig brain membranes was reduced by omission of NaCl but was not affected by omission of MgCl2 or addition of guanosine 5'-(beta-gamma-imido)triphosphate or various pharmacological agents known to interact with other common peptide and nonpeptide receptor systems. [3H]L-365,260 also bound in a specific manner to guinea pig gastric glands but only negligibly to guinea pig or rat pancreas. The binding of [3H]L-365,260 to gastric glands was inhibited by CCK/gastrin antagonists with potencies similar to those for inhibition of 125I-gastrin binding in this tissue. Collectively, the data indicates that [3H]L-365,260 represents a new potent nonpeptide antagonist radioligand suitable for the study of brain CCK-B and gastrin receptors.
The cytosolic isocitrate dehydrogenases (NADP-IDH) were purified to homogeneity from pea roots and green leaves with a high yield by ammonium sulfate precipitation, DEAE-cellulose chromatography, Sephacryl S-200 gel filtration, Matrex red-A affinity chromatography and phenyl-Superose HR 5/5 HPLC. Both isoenzymes were dimeric proteins, consisting of two apparently identical 41-kDa subunits, having similar secondary structures with an alpha-helical content of 20% and a beta-pleated sheet content of 43%. Similarly immunoassays suggested that the two isoenzymes were closely related in terms of antigenic determinants. However, the two proteins were distinguishable by their electrophoretic mobilities and amino acid compositions. The profiles of the two isoenzymes as a function of pH were similar and exhibited a broad pH optimum from 8.5 to 9.0 with Mg2+ as cofactor and 8.0 to 8.5 when Mn2+ was used. Compared to the root isoenzyme, the leaf NADP-IDH appeared to be more heat-labile. However, these isoenzymes exhibited similar behavior for thermal denaturation in the presence of bovine serum albumin and were stabilized upon addition of substrate, metal and coenzyme. Their values of activation energy were estimated as 47 kJ/mol. When using Mn2+ as cofactor, the two isoenzymes displayed identical Km(Mn2+), Km(DL-isocitrate) and Km(NADP) values, which were calculated to be 2.1 microM, 5.7 microM and 2.7 microM respectively. With Mg2+ as cofactor, their Km(Mg2+) K(DL-isocitrate)m and Km(NADP) values were also not statistically different, being 34.0 microM, 15.2 microM and 2.6 microM for the root NADP-IDH, and 29.0 microM, 20.3 microM and 3.1 microM for the leaf isoenzyme. From the above data it can be concluded that although the cytosolic NADP-IDH in pea roots and leaves are organ-specific isozymes, their similar physicochemical and kinetic properties suggest that the two isozymes might be involved in identical metabolic functions.
Transforming growth factor-beta (TGF-beta) inhibits proliferation of Nb2 cells, a rat T lymphoma, in response to lactogens and interleukin-2. Prostaglandins may play an important role in the pathway through which TGF-beta exerts its inhibitory actions, because prostaglandin E2 also inhibits proliferation of Nb2 cells, and indomethacin, an inhibitor of prostaglandin synthesis, reverses the inhibitory effects of TGF-beta on Nb2 cell proliferation.
L-654,284 [2R, 12bS)-N-(1,3,4,6,7,12b-hexahydro-2H-benzo[b]-furo[2,3-a] quinolizin-2-yl)-N-methyl-2-hydroxyethanesulfonamide], a potent and selective antagonist of the alpha 2 adrenoceptor, was tritiated to high specific activity. Saturation binding to cell membrane suspensions obtained from calf cerebral cortex revealed a high affinity binding site (0.63 nM). Kinetics of association and dissociation were well represented by single exponential processes, and the equilibrium dissociation constant obtained from the ratio of rate constants agreed well with that found by saturation binding. A direct comparison of saturation binding revealed that the antagonist [3H]L-654,284 had roughly the same affinity for the alpha 2 adrenoceptor as the agonist [3H]clonidine and eight times the affinity of the antagonist [3H]rauwolscine. The maximum receptor densities of these radioligands were not significantly different. Competition assays with a series of compounds of known receptor affinity revealed that [3H]L-654,284 selectively binds to a site with all of the characteristics expected of the alpha 2 adrenoceptor.
We report an unusual phenotype of B cells in a patient with X-linked agammaglobulinemia (XLA), and cellular evidence for Lyonization of B cells from his mother and sister. The patient has a failure of B cell maturation at the stage of early B lymphocytes, associated with production of D(mu delta) H chain. The phenotype of his B cells includes: (a) limitation to expression of the mu and delta H chain isotypes, (b) production of mu and delta H chains of reduced size and (c) delayed expression of L chain. Peripheral blood and B cell lines from the patient's mother and sister include 50% cells that express H chain without L chain. B cell lines from the mother and sister produce full-length mu and gamma H chains and truncated mu and delta chains corresponding to the H chains produced by the patient's B cells. Clones with normal and XLA phenotype have been isolated from B cell lines derived from the patient's mother. We conclude that the dimorphism of mother's and sister's B cells results from Lyonization, implying that the gene defect in XLA is intrinsic to B lymphocytes.
Sections of human placental villi tissue and carcinoma cell lines (SMMC-7721, (MGC-803 and Kato-111; were examined using the indirect immunoperoxidase histological technique to further investigate the localization of the tumor-associated placental protein (PP) in human placental tissue and the expression of PP on carcinoma cell lines. PP was prepared from placenta in the first trimester. Placental tissue sections exposed to PP antisera showed a marked staining of the trophoblast cells, especially in syncytiotrophoblast. The strongly stained area was localized to the cell membrane of syncytiotrophoblast. In contrast, the nucleus and the cytoplasm of syncytiotrophoblast were stained weakly. The specific PP antisera also stained the carcinoma cell lines. Among different carcinoma cell lines, the degree of staining of liver carcinoma cell line (SMMC-7721) was higher than that of gastric carcinoma cell lines (MGC-803 and Kato-111). In the carcinoma cell lines the presence of antigen similar to PP suggests that oncogene (one) occur in human trophoblast cells as well as mice trophoblast cells.
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The convenience of the previously described enzyme immunochromatography method for visually quantifying theophylline in whole blood has been improved with the development of a one-step protocol. The capillary migration and color generation in the two-step enzyme immunochromatographic assay have been combined into a single step. Ascorbic acid is used as a signal inhibitor to delay enzymatic color product formation until the inhibitor itself is consumed. The concept of internal delay reaction is presented and the mechanism of ascorbate's action as an inhibitor to temporarily delay color generation is described. The internal delay reaction has been applied to a practical one-step quantitative visual enzyme immunochromatographic assay for theophylline in whole blood.