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Biomedical subjects

H Cai

Publications and source records attributed to H Cai.

At least 163 records · Page 9Linked to original sources
PubMed1995

Phosphate transport inhibition by KW-3902, an adenosine A1 receptor antagonist, is mediated by cyclic adenosine monophosphate.

We have previously demonstrated that 1,3-dipropyl-8-(3-noradamantyl) xanthine (KW-3902) has an inhibitory effect on phosphate (Pi) transport with no effect on glucose transport in the rat renal proximal tubular cell, similar to that of parathyroid hormone (PTH). In the current studies we investigated the effect of KW-3902, rat PTH (1-34), and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), another selective adenosine A1 receptor antagonist, on Pi transport and the production of cyclic adenosine monophosphate (cAMP). We then compared these effects of KW-3902 with those of rat PTH in rat renal proximal tubule cells. The results showed that both KW-3902 (30 mumol/L) and rat PTH (1-34, 5 mumol/L) significantly inhibited Pi uptake in proximal cells from a control level of 61 +/- 3 to 19 +/- 3 (a reduction of 69%) and 46 +/- 4 picomoles phosphate/mg protein/min (a reduction of 25%), respectively (P < 0.01). The inhibitory effect of 30 mumol/L KW-3902 alone on Pi transport was more than twice that of 5 mumol/L rat PTH (1-34) alone (P < 0.01). KW-3902 stimulated the production of cAMP in a dose-dependent manner (r = 0.997, P < 0.01). Rat PTH (1-34; 5 mumol/L) also stimulated cAMP production, which was greater than that induced by 30 mumol/L KW-3902 alone. A significant increase in cAMP production by 30 mumol/L DPCPX was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Race: a Drosophila homologue of the angiotensin converting enzyme.

We report the isolation and characterization of a putative angiotensin converting enzyme (ACE) in Drosophila, called Race. General interest in mammalian ACE stems from its association with high blood pressure; ACE has also been implicated in a variety of other physiological processes including the processing of neuropeptides and gut peristalsis. Mammalian ACE is a membrane associated zinc binding protease that converts angiotensin I (A I) into angiotensin II (A II). A II functions as a potent vasoconstrictor by triggering a G-coupled receptor system in the smooth muscles that line blood vessels. Drosophila Race is composed of 615 amino acid residues, and shares extensive sequence identity with mammalian ACE over its entire length (over 42% overall identity and greater than 60% similarity). Evidence is presented that Race might correspond to a target of the homeobox regulatory gene, zerknullt (zen). Soon after zen expression is restricted to the dorsal-most regions of the embryonic ectoderm, Race is activated in a coincident pattern and becomes associated with the amnioserosa during germ band elongation, shortening and heart morphogenesis. After germ band elongation, Race is also expressed in both the anterior and posterior midgut, where it persists throughout embryogenesis. Race expression is lost from the dorsal ectoderm in either zen- or dpp- mutants, although gut expression is unaffected. P-transformation assays and genetic complementation tests suggest that Race corresponds to a previously characterized lethal complementation group, 1(2)34Eb. Mutants die during larval/pupal development, and transheterozygotes for two different lethal alleles exhibit male sterility. We propose that Race might play a role in the contractions of the heart, gut, or testes and also suggest that Hox genes might be important for coordinating both developmental and physiological processes.

Amino Acid Sequence↗
PubMed1995

CBI-CDPBO1 and CBI-CDPBI1: CC-1065 analogs containing deep-seated modifications in the DNA binding subunit.

The synthesis and preliminary examination of CBI-CDPBO1 (2) and CBI-CDPBI1 (3), CBI analogs of CC-1065 (1) and the duocarmycins incorporating the 3-carbamoyl-1,2-dihydro-3H-pyrrolo[3,2-e]benzoxazole-7-carboxylate (CDPBO) and 3-carbamoyl-1,2-dihydro-3H-pyrrolo[3,2-e]benzimidazole-7-carboxylate (CDPBI) DNA binding subunits, are detailed. The agents contain deep-seated modifications in the DNA binding subunits of the natural products with incorporation of a nitrogen capable of functioning as a hydrogen bond acceptor (CDPBO, CDPBI) or hydrogen bond donor (CDPBI) on their inside concave face which is in intimate contact with the minor groove floor. The CDPBO subunit was prepared through use of a novel and effective MnO2-mediated oxidative coupling of 2-(benzyloxy)ethylamine with 5-hydroxyindole (4) to directly provide 2-[(benzyloxy)methyl]pyrrolo[3,2-e]benzoxazole (6, 48%) in a reaction cascade that initially proceeds with amine regioselective C4 nucleophilic addition to the in situ generated p-quinone monoimine 13. Subsequent conversion of 6 to 8 (debenzylation; MnO2-NaCN, CH3OH) and selective reduction of the fused pyrrole (Et3SiH-CF3CO2H) completed the synthesis of the 1,2-dihydro-3H-pyrrolo[3,2-e]benzoxazole-7-carboxylate ring system. The CDPBI subunit was prepared through selective C4 nitration of 22 followed by reduction of the nitro group and acid-catalyzed closure to the corresponding 2-[(benzyloxy)methyl]pyrrolo[3,2-e]benzimidazole 25. The final conversion of 25 to the 1,2-dihydro-3H-pyrrolo[3,2-e]benzimidazole-7-carboxylate ring system (CDPBI) followed the same protocols introduced for CDPBO. The DNA alkylation efficiencies of 2 and 3 were identical and both were substantially diminished relative to that of CBI-CDPI1 (40). Thus, the introduction of a single nitrogen atom in the DNA binding subunit of 40 has a pronounced and detrimental effect on the relative efficiency (100 x) of DNA alkylation. Consistent with these observations, the in vitro cytotoxic activity of (+)-2 and (+)-3 were comparable (IC50 = 200 pM, L1210) and 40 x less potent than (+)-40 (IC50 = 5 pM, L1210). In contrast to the large impact these small structural changes had on the efficiency of DNA alkylation, the selectivity of DNA alkylation by 2 and 3 was unperturbed and both agents were found to alkylate the same major sites as CBI-CDPI1 (40). The potential origin of these effects is discussed.

Alkylation↗
PubMed1995

Study on anti-cataract drugs from natural sources. II. Effects of buddlejae flos on in vitro aldose reductase activity.

The inhibitory effects of nine crude drugs were tested on unpurified rat lens aldose reductase, an enzyme involved in the complications of diabetes. Among the crude drugs, a 70% methanolic extract of Buddlejae Flos (flower of Buddleja officinalis) exhibited the highest inhibition. Luteolin, luteolin-7-O-beta-D-glucopyranoside, apigenin and acacetin-7-O-alpha-L-rhamnopyranosyl-(6-1)-beta-D-glucopyranoside isolated from Buddlejae Flos showed the inhibitory activity, the IC50 (concentration of 50% inhibitory percentage) values of which were 0.21, 0.28, 0.58 and 0.75 microM, respectively. It is suggested that the inhibitory effect of Buddlejae Flos on aldose reductase is partially attributable to these flavonols or their glycosides.

Aldehyde Reductase↗
PubMed1995

[Immunohistochemical study of epidermal growth factor in liver of mice infected with schistosoma japonicum].

In this immunohistochemical study we examined the expression and localization of the epidermal growth factor in liver of mice infected with schistosoma japonicum during regulatory phase of immunology and early phase of hepatic fibrosis. EGF immunostaining is localized along sinusoids and within cytoplasm of centrilobular area and around ova granuloma at 6,8 weeks of infection. Proliferation of Ito cells and collagen deposition in Disse space were found by electron microscope. The data led us to conclude that the ova depositing in liver could excite the release of EGF and cytokines, then promote proliferation of Ito cells and overgrowth of extracellular matrix (ECM) under the endothelium, resulting in hepatic fibrosis.

Animals↗
PubMed1995

[The relationship between 4-hydroxynonenal-derived epitopes on apolipoprotein B and coronary heart disease].

When lipid peroxidation takes place in plasma low density lipoprotein (LDL), a lot of aldehydes-derived epitopes are generated. To explore the relationship between these aldehydes-derived epitopes on apolipoprotein B (apo B) and coronary heart disease (CHD), we used both antibody against 4-hydroxynonenal (HNE)-derived epitopes and antibody against apo B to establish a sandwich enzyme-linked immunoassay (ELISA). The sera from 160 normal controls as well as from 103 patients with CHD were tested by ELISA for the expression of HNE-derived epitopes on apo B. The measurements showed that the mean expression of HNE-epitopes in the patients with CHD (183.5 +/- 63.6 mg/L, n = 103) was higher than that of normal controls (133.3 +/- 47.5 mg/L, n = 160). The difference of the expression of HNE-epitopes on serum apo B between the patients and normal controls was statistically significant. The results analysed by a multiple regression demonstrated that the expression of HNE-epitopes, levels of LDL-cholesterol and age were positively related to CHD, while the levels of HDL-cholesterol and female were negatively related to CHD. Thus, it was proven for the first time that the enhanced expression of HNE-epitopes on apo B might be an independent risk factor of CHD.

Aldehydes↗
PubMed1995

[Confocal laser scan microscope system and its applications on studying acupuncture and meridian].

In this paper, the principle of a confocal laser scan microscope system and its advantages are introduced. Its applications in biology and research of acupuncture and meridian are also introduced. Compared with conventional microscope, the confocal laser scan microscope system has many advantages such as high resolution fluorescent image, 3-dimension reconstruction, images quantitative analysis of concentration of ion within a cell, cell-cell communication and so on. It will offer many mathods for researching acupuncture and meridian.

Acupuncture Therapy↗
PubMed1995

[Histochemical observation of the effect of electroacupuncture on the livers of rats with endotoxic shock].

The experimental rats were randomly divided into three groups: i.e. control group; endotoxic shock group (the model of endotoxic shock was induced by intravenous administration of E. Coli endotoxin, 16 mg/kg); and electroacupuncture (EA) group ("Renzhong" or "Zusanli" acupoint was stimulated for 15 minutes at 1 hr after injection of endotoxin). The experimental rats were decapitated at 75 minutes after injecting endotoxin. Their livers were taken out for cryostat section, and histochemical observation. The results were as follows: 1) The glycogen in the hepatic cells of endotoxic shocked rats were almost completely depleted. The activities of SDH Mg(++)-ATPase and G-6-Pase and 5'-Nase were decreased; especially the activities of 5'-Nase in the biliary canaliculi and sinusoids were apparently reduced. 2) The content of hepatic glycogen in EA group was increased, but some of them was still depleted. The activities of SDH, Mg(++)-ATPase and G-6-Pase were slightly increased as compared with that of the endotoxic shock group. The activity of 5'-Nase was obviously increased after EA. The preliminary results indicated that EA at "Renzhong" or "Zusanli" acupoint of rats with endotoxic shock might play certain role on improving the hepatic metabolism and promoting the membrane transport action.

Animals↗
PubMed1995

[The visual evoked potentials of non-amblyopic eyes in children with amblyopia].

We investigated the characteristics of visual evoked potentials (VEPs) of the eyes with normal visual acuity in 84 children of whom 20 were normal, 28 of anisometropic amblyopia, 8 of anisometropic amblyopia already cured, 8 pairs of monozygotic and 6 pairs of dizygotic twins with amblyopia. The results showed that although the fellow eye of an amblyopic eye or the cured amblyopic eye had normal visual acuity, the VEPs presented abnormal, the marked abnormality being the prolongation of the latency of P100 peak. No significant difference was found in VEPs between the eye with normal visual acuity and the eye with amblyopia in the monozygotic twins with the same genetic background (P > 0.05). This study demonstrated that possibly the clinical examinations of visual acuity and VEPs reflect different visual information processes, and the "normal" eyes of amblyopes are not normal.

Amblyopia↗
PubMed1994

Chaperone-like activity of protein disulfide isomerase in the refolding of a protein with no disulfide bonds.

D-Glyceraldehyde-3-phosphate dehydrogenase (GAP-DH) is a protein containing no disulfide bonds; the guanidine HCl-denatured enzyme shows only a limited extent of refolding and reactivation upon dilution, and the enzyme is particularly prone to aggregation during the dilution process. With increasing GAPDH concentration, reactivation decreases and aggregation increases. The presence of protein disulfide isomerase in the dilution mixture markedly increases reactivation of GAPDH and at the same time prevents the aggregation of GAPDH as shown by light-scattering measurements. It is suggested that upon dilution, denatured GAPDH is faced with two competing processes of correct folding and assembly to yield the native enzyme and non-productive association of the partially refolded species to form aggregates. Independent of the isomerase activity as no disulfide bond is present in GAPDH, protein disulfide isomerase assists the refolding of GAPDH to its active state by suppressing aggregation in a way closely similar to the action of chaperones.

Disulfides↗
PubMed1994

Nucleotide insertion and primer extension at abasic template sites in different sequence contexts.

Efficiencies of insertion and extension at a single site-directed abasic lesion, X, were measured while varying 5'- and 3'-template bases adjacent to X. The preference for insertion was found to be A > G > T approximately C, with the "upstream" (3'-neighboring) template base perturbing insertion efficiencies by an order of magnitude or more. Efficiencies of synthesis past the abasic lesion depended strongly on the "downstream" (5'-neighboring) template base and on the properties of the polymerase. HIV-1 RT favored "direct" extension of X.A > X.G > X.T > X.C, by addition of the next correct nucleotide. However, it was found that X.C, least favored for direct extension, was most favored for "misalignment" extension, occurring when the DNA structure in the vicinity of the lesion collapsed to realign a primer 3'-C terminus opposite a downstream template G site. Polymerase properties have an important role in copying abasic lesions. Drosophila DNA polymerase alpha, HIV-1, and AMV reverse transcriptases had "little" difficulty inserting opposite abasic lesions, with efficiencies comparable to misinsertions opposite normal template bases. However, AMV RT did not extent past the lesion using direct or misalignment mechanisms. Wild-type and mutant T4 DNA polymerases were used to show that although exonucleolytic proofreading inhibits lesion bypass, the presence of a highly active proofreading exonuclease is not sufficient to prevent bypass.

DNA Damage↗
PubMed1994

Effect of KW-3902, a novel adenosine A1 receptor antagonist, on sodium-dependent phosphate and glucose transport by the rat renal proximal tubular cell.

KW-3902, 1,3-dipropyl-8-(3-noradamantanyl)xanthine, is a novel potent and selective adenosine A1-receptor antagonist. KW-3902 has been found to cause significant diuresis and natriuresis. To investigate the action of this adenosine A1-receptor antagonist on phosphate transport in renal proximal tubular cells, we studied its effect on the uptake of phosphate by the cultured rat renal proximal tubular cell. KW-3902 significantly inhibited sodium-dependent uptake of phosphate at 10 minutes. The inhibitory effect was dose-dependent with maximum effect achieved at a KW-3902 concentration of 3 x 10(-5) M in the uptake media. The half-maximal inhibitory concentration, IC50, of KW-3902 on phosphate uptake was 2 x 10(-6) M. Dixon plot analysis of the uptake data was consistent with pure non-competitive inhibition. The inhibition constant, Ki, of 6.2 x 10(-6) M for phosphate transport, derived from the Dixon plot, was in close agreement with the IC50 calculated from a semilog dose response curve. Sodium-dependent glucose transport was not affected by KW-3902. These findings reveal that KW-3902 has a direct and specific inhibitory effect on phosphate uptake in renal proximal tubules.

Animals↗
PubMed1994

A yeast artificial chromosome clone map of the Drosophila genome.

We describe the mapping of 979 randomly selected large yeast artificial chromosome (YAC) clones of Drosophila DNA by in situ hybridization to polytene chromosomes. Eight hundred and fifty-five of the clones are euchromatic and have primary hybridization sites in the banded portions of the polytene chromosomes, whereas 124 are heterochromatic and label the chromocenter. The average euchromatic clone contains about 211 kb and, at its primary site, labels eight or nine contiguous polytene bands. Thus, the extent as well as chromosomal position of each clone has been determined. By direct band counts, we estimate our clones provide about 76% coverage of the euchromatin of the major autosomes, and 63% coverage of the X. When previously reported YAC mapping data are combined with ours, euchromatic coverage is extended to about 90% for the autosomes and 82% for the X. The distribution of gap sizes in our map and the coverage achieved are in good agreement with expectations based on the assumption of random coverage, indicating that euchromatic clones are essentially randomly distributed. However, certain gaps in coverage, including the entire fourth chromosome euchromatin, may be significant. Heterochromatic sequences are underrepresented among the YAC clones by two to three fold. This may result, at least in part, from underrepresentation of heterochromatic sequences in adult DNA (the source of most of the clones analyzed), or from clone instability.

Animals↗
PubMed1994

Immunomodulatory effect of fu-fang-tai-pan-pian, a traditional Chinese tonic medicine.

The purpose of this study was to evaluate the effect of the traditional Chinese medicine Fu-Fang-Tai-Pan-Pian on responsiveness of mouse spleen leukocytes to the mitogens concanavalin A (con A), phytohemagglutinin (PHA), and bacterial endotoxin (LPS). Aqueous and chloroform/methanol extracts of the drug were prepared and added to mitogen-stimulated cultures at doses ranging from 0.625% to 20% by volume. The aqueous extract depressed responsiveness to all mitogens at all doses tested, and was significantly more potent in this regard than the organic extract. The organic extract depressed responsiveness at low dilutions; however it significantly stimulated responsiveness to PHA and LPS, but not to con A, at dilutions of 2.5% or less. The relative ability of compounds partitioning into aqueous and organic extracts of the medicinal mixture to both stimulate and depress the ability of lymphocytes to proliferate may provide insight into the mechanism of action of this and related medicines.

Analysis of Variance↗
PubMed1994

Effect of moderate hypothermia on lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation.

BACKGROUND AND PURPOSE: We sought to examine the effect of moderate hypothermia (30 degrees C to 32 degrees C) initiated after resuscitation on the scavenging systems of free radicals and lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation. METHODS: Twenty-one dogs were divided into four groups: group A, nonischemic controls (shams) (n = 4); group B, 15-minute cardiac arrest without reperfusion (n = 4); group C, 15-minute cardiac arrest and standard resuscitation (n = 6); and group D, 15-minute cardiac arrest and hypothermic resuscitation (n = 7). During the period of 10 to 120 minutes after resuscitation, brain temperature and core temperature in group D remained at 30 degrees C to 32 degrees C and were 4 degrees C to 5 degrees C lower than in group C. For each dog, a sample of right parietal cerebral cortex was obtained from group A, group B, or from group C and group D at 2 hours after resuscitation. The sample was assayed for tissue malondialdehyde (MDA), the content of reduced glutathione (GSH), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). RESULTS: In group B, a 15-minute cardiac arrest induced an increase in MDA, a significant reduction of GSH, and no change in SOD and GSH-PX activities compared with group A. In group C, there were further increases in MDA and reductions in GSH content and GSH-PX activity compared with group A; SOD activity remained substantially unchanged. The content of MDA was higher in group D than in group A but less elevated in group D than in group C. The GSH content and SOD and GSH-PX activities were significantly higher in group D than in group C. CONCLUSIONS: Moderate hypothermia initiated after resuscitation can significantly inhibit the accumulation of lipid peroxidation products and the consumption of free radical scavengers in the brain tissue.

Animals↗