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Biomedical subjects

J Z Guo

Publications and source records attributed to J Z Guo.

At least 37 records · Page 2Linked to original sources

[Pharmacokinetics and pharmacodynamics of slow release tablet of diltiazem in hypertensive patients with various renal functions].

Twenty hypertensive patients were equally divided into 2 groups: A) with normal renal function (NRF) and B) with impaired renal function (IRF) according to creatinine clearance, blood urea nitrogen and creatinine levels. The pharmacokinetic and pharmacodynamic effects of diltiazem (Dil, 90 mg, bid x 7 d, p.o.) were studied. The pharmacokinetic parameters in IRF patients (Ka 0.7 +/- 0.2 h-1, T 1/2e 3.7 +/- 0.7 h, Cmax1 45 +/- 4 ng.ml-1, Tmax1 3.1 +/- 0.4 h) did not differ from those in NRF patients (0.7 +/- 0.5 h-1, 4.1 +/- 1.3 h, 41 +/- 5 ng.ml-1 and 3.4 +/- 0.4 h, P > 0.05). Antihypertensive efficacy of Dil in patients with IRF was similar to that in those with NRF, and the hypotensive effect lasted over 24 h. The plasma Dil concentrations were strongly correlated with a decrease in BP in both groups. It was concluded that IRF did not affect the disposition of slow release Dil tablet under a steady state. No dosage adjustment of Dil is necessary in hypertensive patients with IRF.

Adult↗

Electrophysiological identification of horizontal synaptic connections in rat visual cortex in vitro.

The presence of intrinsic horizontal synaptic connections in rat visual cortex was explored electrophysiologically using in vitro slice preparations. Intracellular recordings were made from pyramidal neurons located in the superficial and deep layers. Electrical stimulation at the gray matter in the same or different layers but 0.8-2.7 mm apart from the recording site evoked compound synaptic potentials composed of excitatory and inhibitory postsynaptic potentials of fast and slow time courses. Glutamate blockers, DNQX (5 microM) and kynurenate (2 mM) reduced the excitatory postsynaptic potential (EPSP), and GABAB receptor antagonist, phaclofen (0.5 mM), abolished the inhibitory postsynaptic potential of the slow time course. EPSP of the fast time course followed 20 Hz repetitive stimulation in the medium of high Ca2+ (6.0 mM) and Mg2+ (4.0 mM) concentration, suggesting that this fast EPSP was monosynaptic. Conduction velocity of the fibers mediating the monosynaptic EPSP was estimated to be 0.15-0.55 m/s. These results provide physiological evidence for the horizontal synaptic connections in the rat visual cortex, which had been previously suggested by morphology.

Animals↗

Involvement of NK1 receptors in synaptic transmission in the guinea pig coeliac ganglion.

Using intracellular recording techniques, we examined the effects of tachykinin receptor agonists and antagonists on electrophysiologically identified tonic neurons of the isolated guinea pig coeliac ganglion. In most of the tonic neurons, substance P (SP), neurokinin A (NKA) and/or senktide induced a depolarization. The effects of SP and NKA were blocked by the NK1-selective antagonist, GR71251 (5 microM), but not by the NK2-selective antagonist, L659,877 (10 microM), whereas the effect of senktide was not affected by these antagonists. The NK1-selective agonists, [Sar9,Met(O)2(11)]SP and SP methyl ester, and the NK3-selective agonist, [MePhe7]neurokinin B, also evoked depolarizations in tonic neurons. By contrast, the NK2-selective agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, at 1 microM each, did not evoke any significant depolarizing response. Repetitive electrical stimulation of the mesenteric nerves induced slow excitatory postsynaptic potentials (EPSPs) in the majority of tonic neurons, which were depressed by GR71251 (5 microM). These results suggest that NK1 and NK3 receptors but not NK2 receptors are involved in the tachykinin-induced depolarization of tonic neurons, and that the NKA-induced response is due to the activation of NK1 receptors. This study also suggests the involvement of NK1 receptors in the slow EPSPs in tonic neurons.

Animals↗

Depression of primary afferent-evoked responses by GR71251 in the isolated spinal cord of the neonatal rat.

1. The pharmacological profile of GR71251, a new tachykinin receptor antagonist, and its effect on the responses evoked by stimulation of primary afferent fibres were studied in isolated spinal cord preparations of neonatal rats. Potential changes were recorded extracellularly from a lumbar ventral root (L3-L5). 2. Bath-application of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) at 0.01-3 microM to the spinal cord induced depolarization of the ventral root in normal artificial cerebrospinal fluid (CSF). The NK1 agonist, acetyl-Arg6-septide, and the NK3 agonist, senktide, at 0.01-3 microM, also had potent depolarizing actions whereas two NK2 agonists, beta-Ala8NKA4-10 and Nle10NKA4-10, showed little depolarizing effects at 1 microM. 3. GR71251 (0.3-3 microM) caused a rightward shift of the concentration-response curves for SP, acetyl-Arg6-septide and NKA with pA2 values of 6.14, 6.75 or 6.70, respectively. The effects of GR71251 were readily reversible within 15-30 min after its removal. By contrast, GR71251 (1-5 microM) had little effect on the depolarizing responses to NKB and senktide. 4. GR71251 (1-3 microM) did not depress the depolarizing responses to bombesin, neuromedin B and gastrin-releasing peptide in normal artificial CSF. 5. Application of capsaicin to the spinal cord induced a depolarizing response, which was partially depressed by GR71251 (3-10 microM). 6. In the isolated spinal cord preparation, intense electrical stimulation of a dorsal root evoked a slow depolarizing response of the contralateral ventral root of the same segment. A similar slow ventral root depolarization was evoked by electrical stimulation of the ipsilateral saphenous nerve in an isolated spinal cord-saphenous nerve preparation. GR71251 (0.3-10 microM) dose-dependently depressed these slow ventral root potentials.7. In the spinal cord-peripheral nerve preparation, conditioning stimulation of the saphenous nerve evoked an inhibition of the muscle nerve-evoked monosynaptic reflex lasting about 20 s. The late part of the inhibition was markedly depressed by GR71251 (1-3 microM).8. The present results indicate that GR71251 is a potent and specific antagonist for tachykinin receptors in the spinal cord. The present study further provides evidence for the involvement of SP and NKA in the slow ventral root depolarization and the prolonged inhibition of monosynaptic reflex that are evoked by primary afferent stimulation.

Analgesics↗

Differential expression of the alpha 2 and beta messenger RNAs of Na,K-ATPase in developing brine shrimp as measured by in situ hybridization.

We used in situ hybridization histochemistry with synthetic oligonucleotide probes to localize the mRNAs encoding the alpha 2- and beta-mRNAs of Na,K-ATPase during development of the brine shrimp Artemia. The mRNAs of the alpha 2- and beta-subunit were of low abundance in the cysts; in addition, less mRNA of the beta-subunit was localized. During emergence (12 hr), there was an increase in alpha 2-subunit mRNA in the gut mucosa, but there was a burst in beta-subunit mRNA throughout. As development progressed, the mRNAs of both the alpha 2- and beta-subunits showed a distinct pattern of expression in which the mRNA in the salt gland was of greatest abundance, followed by epidermal cells and gut mucosa. After 36 hr the alpha 2-subunit mRNA began to decrease in all positive cells but still remained highest in the salt gland and the brain region, while the mRNA of the beta-subunit kept increasing in the gut mucosa. Finally, the greatest abundance of the beta-subunit mRNA shifted from the salt gland to the antenna gland and the epidermal cells in the tail region, but the alpha 2-subunit mRNA did not. The more widespread distribution of the beta-mRNA than alpha 2-mRNA at certain stages (e.g., there was no alpha 2-mRNA in the antenna gland at the adult stage) is in all likelihood due to the marked drop in the alpha 2-subunit and a rise in alpha 1-subunit previously seen by Peterson et al. on polyacrylamide gel electrophoresis, as development progresses.

Animals↗

[Pharmacokinetics and pharmacodynamics of diltiazem floating tablets].

Floating tablet is a new type of delayed-action preparations. The present study was aimed at pharmacokinetic and hemodynamic effects of diltiazem floating tablet in 8 healthy volunteers. Each subject received po 90 mg diltiazem floating and normal tablets in a crossover design. For floating tablets the T1/2 (6.4 +/- 4.4 h) and Cmax (56 +/- 23 ng.ml-1) were longer and lower than those of normal tablets (2.3 +/- 1.1 h and 96 +/- 30 ng.ml-1, P < 0.01), respectively. AUC of the 2 forms were similar, suggesting that they had same bioavailability. Diltiazem lowered the blood pressure of the subjects. Although there was no significant difference between the 2 formulations in maximal decreases of systolic and diastolic blood pressures, the duration of hypotension was longer with floating tablets than that with normal ones. There was a positive correlation between diltiazem concentration and its hypotensive action. Thus, administration of floating tablets twice a day may be effective in controlling the blood pressure of hypertensive patients.

Adult↗

Na,K-ATPase expression in the developing brine shrimp Artemia. Immunochemical localization of the alpha- and beta-subunits.

Developing brine shrimp are a good experimental model for study of gene expression during development. Development is initiated on suspension of brine shrimp cysts in seawater. Only 48 hr are required for progression from cyst to the larval stage. We have localize the alpha- and beta-subunits in different cells by immunostaining as development progresses. Both alpha- and beta-subunits are first detected in epidermal cells in the trunk region at the emergence 2 stage (16-hr incubation). At the nauplius 1 stage (24 hr) the enzyme appears in the brain and epidermal regions, as well as in mesenchymal cells, with weaker staining in the salt gland. After further development (nauplius 2 stage, 36 hr) stronger staining appears in the salt gland and in the epidermal region. At the nauplius 3 stage (48 hr) the enzyme appears in the midgut mucosa. Co-localization of the alpha- and beta-subunits appears in all positive cells during development. In the epidermal and salt gland cells the enzyme is mainly localized on the basolateral membrane. The basolateral localization of the Na,K-ATPase in epidermal and salt gland cells suggests that Na+ is actively transported into the epidermal and salt gland cells and passively diffuses out from the apical region.

Animals↗

Messenger RNA stabilization accounts for elevated basic fibroblast growth factor transcript levels in a human astrocytoma cell line.

Basic fibroblast growth factor (bFGF) is a potent autocrine and paracrine mitogen for cells of mesodermal origin. Although the protein is present in substantial amounts in a variety of tissues, the level of mRNA is undetectable in most normal tissues. This has led to speculation that bFGF mRNA is very unstable, but the half-life of this mRNA has not been described. A number of mRNAs encoding growth factors and growth-related proteins are known to be short-lived and posttranscriptionally regulated. In the present study we have examined the half-life of bFGF mRNA in two human tumor cell lines, which contain high (U87-MG) and low (T98-G) steady state bFGF mRNA levels. The half-life of bFGF mRNA, determined after transcriptional arrest with actinomycin-D, was approximately 10 min in T98-G cells, but was extended to 120 min in the presence of cycloheximide. In contrast, bFGF transcripts in U87-MG cells were very stable with a half-life considerably greater than 5 h. This was not attributable to a general stabilization of mRNA in the U87-MG line, since the half-life of c-myc mRNA in the two cell lines was similar (10 and 15 min in T98-G and U87-MG, respectively). Cycloheximide had no effect on the steady state level of bFGF in U87-MG cells. These findings suggest that posttranscriptional processes play an important role in the regulation of bFGF transcript levels and demonstrate that loss of posttranscriptional regulation could contribute to elevated bFGF expression in some tumors.

Astrocytoma↗

Molecular cloning of the Na,K-ATPase alpha-subunit in developing brine shrimp and sequence comparison with higher organisms.

We report here the molecular cloning, nucleotide sequence, and predicted amino acid sequence of an alpha-subunit of the developmentally useful model, Artemia. The amino acid sequence shows divergence from that of mammals, birds, Torpedo, and Drosophila. However, regions in the putative ATP binding and transmembrane domains show absolute or high levels of conservation. Major differences occur in the amino-terminal domain and several other hypervariable regions. These differences are consistent with the suggestion that the brine shrimp is a 'fast clock' organism which diverged from the precursors of vertebrates 0.5-1 billion years ago.

Amino Acid Sequence↗

Estrogen effects on modifications of chromatin proteins in the rat uterus.

ADP-ribosylation and phosphorylation of chromatin proteins was studied in rat uterine nuclei isolated after estrogen treatment and then incubated with [adenylate-32P]NAD or [gamma-32P]ATP. Histone acetylation was studied in uteri from immature rats treated with estradiol by incubating the whole uterus in a medium containing [14C]acetic acid. Chromatin proteins were isolated from uterine nuclei and separated by electrophoresis on SDS polyacrylamide gels followed by autoradiography or fluorography. Chromatin proteins H1, H2B, H3, HMG 14 and HMG 17 were almost exclusively ADP-ribosylated. Uterine histones H1, H3, H4, HMG 14 and HMG 17 were phosphorylated. There was a general increase in [32P]ADP-ribose uptake in chromatin proteins after estrogen stimulation, whereas [32P]phosphate incorporation into chromatin proteins showed a biphasic pattern. The [14C]acetate activity associated with all histone proteins increased gradually after estrogen treatment.

Acetylation↗

Malignant pheochromocytoma: diagnosis and treatment in fifteen cases.

This study reviews the diagnosis and treatment of 15 patients with malignant pheochromocytoma (MP) between 1958 and 1986 in Shanghai Rui-jin Hospital. The main clinical features consisted of sustained elevation of arterial blood pressure, obviously increased catecholamine secretion and a sustained positive phentolamine test. Out of 15 patients only seven survived, two of whom suffered from paraplegia due to metastatic cordal compression. Compared with some earlier results, the prognosis was unsatisfactory. There were several factors which may have been responsible: (1) late diagnosis; (2) incomplete operation, and (3) no regular post-operative assessment of urinary biochemical changes. Because MP is a tumour with a low degree of malignancy, noting the above three factors and using 131I-MIBG to obtain accurate diagnosis and effective treatment enables a better prognosis of this disease.

Adolescent↗

Salt and the action of calcium antagonists.

Calcium antagonists are unique in that they combine vasodilating and natriuretic properties. Although the acute natriuretic response, and details on intrarenal mechanisms of action, have been documented in the past, recent evidence shows intrarenal actions even in the chronic steady state of antihypertensive medication. Chance observations led to recent systematic studies that clearly document (a) that the antihypertensive action of calcium antagonists is not antagonized by high sodium diet and (b) that there is negative interaction between diuretics and calcium antagonists with respect to their antihypertensive actions. Potential mechanisms for the salt/diuretic-calcium antagonist interactions include (i) intrinsic natriuretic property of calcium antagonists, (ii) interaction of volume control and hormonal calcium control systems, and (iii) modulation of--at least dihydropyridine--binding sites by dietary sodium.

Calcium Channel Blockers↗

Differential stimulation of histone and high mobility group chromatin protein synthesis in the rat uterus by estrogen.

Uterine tissue isolated from immature rats at different times after estradiol injection was incubated with medium containing [3H]lysine. The acid-extractable protein from the uterine tissue was subjected to electrophoresis on sodium dodecyl sulfate and acid-urea-Triton X-100 polyacrylamide gels, and the rate of chromatin protein synthesis determined by densitometric analysis of the fluorographs of the gels. Synthesis of chromatin proteins (histones and high mobility group chromatin proteins) was stimulated by 3 h after estrogen treatment and reached a peak at 9 h, several hours before DNA synthesis was stimulated. Synthesis of chromatin proteins occurred at the same time as total cellular protein synthesis. Estrogen stimulated the synthesis of histone variants at different rates, but the accumulation of histone proteins remained coordinated such that equivalent amounts of histone proteins were being produced at any one time.

Animals↗