Biomedical subjects

C Hui

Publications and source records attributed to C Hui.

At least 37 records · Page 2Linked to original sources

PubMed1997

Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development.

The correct patterning of vertebrate skeletal elements is controlled by inductive interactions. Two vertebrate hedgehog proteins, Sonic hedgehog and Indian hedgehog, have been implicated in skeletal development. During somite differentiation and limb development, Sonic hedgehog functions as an inductive signal from the notochord, floor plate and zone of polarizing activity. Later in skeletogenesis, Indian hedgehog functions as a regulator of chondrogenesis during endochondral ossification. The vertebrate Gli zinc finger proteins are putative transcription factors that respond to Hedgehog signaling. In Drosophila, the Gli homolog cubitus interruptus is required for the activation of hedgehog targets and also functions as a repressor of hedgehog expression. We show here that Gli2 mutant mice exhibit severe skeletal abnormalities including cleft palate, tooth defects, absence of vertebral body and intervertebral discs, and shortened limbs and sternum. Interestingly, Gli2 and Gli3 (C.-c. Hui and A. L. Joyner (1993). Nature Genet. 3, 241-246) mutant mice exhibit different subsets of skeletal defects indicating that they implement specific functions in the development of the neural crest, somite and lateral plate mesoderm derivatives. Although Gli2 and Gli3 are not functionally equivalent, double mutant analysis indicates that, in addition to their specific roles, they also serve redundant functions during skeletal development. The role of Gli2 and Gli3 in Hedgehog signaling during skeletal development is discussed.

Animals↗

PubMed1997

A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh in vitro.

The floor plate plays important roles in ventral pattern formation and axonal guidance within the neural tube of vertebrate embryos. A critical event for floor plate development is the induction of a winged helix transcription factor, Hepatocyte Nuclear Factor-3beta (HNF-3beta). The enhancer for floor plate expression of HNF-3beta is located 3' of the transcription unit and consists of multiple elements. HNF-3beta induction depends on the notochord-derived signal, Sonic hedgehog (Shh). Genetic analysis in Drosophila has led to the identification of genes involved in the Hh signalling pathway, and cubitus interruptus (ci), encoding a protein with five zinc finger motifs, was placed downstream. In the present work, we test the involvement of Gli proteins, the mouse homologues of Ci, in activation of the floor plate enhancer of HNF-3beta. Transgenic analysis shows that a Gli-binding site is required for the activity of the minimal floor plate enhancer of HNF-3beta in vivo. Three Gli genes are differentially expressed in the developing neural tube. Gli expression is restricted to the ventral part, while Gli2 and Gli3 are expressed throughout the neural tube and dorsally, respectively. Strong Gli and Gli2, and weak Gli3 expressions transiently overlap with HNF-3beta at the time of its induction. Consistent with ventrally localized expression, Gli expression can be up-regulated by Shh in a cell line. Finally, the Gli-binding site acts as a Shh responsive element, and human GLI, but not GLI3, can activate this binding site in tissue culture. Taken together, these findings suggest that Gli, and probably also Gli2, are good candidates for transcriptional activators of the HNF-3beta floor plate enhancer, and the binding site for Gli proteins is a key element for response to Shh signalling. These results also support the idea that Gli/Ci are evolutionary conserved transcription factors in the Hedgehog signalling pathway.

Animals↗

PubMed1996

Poly(ethylene glycol)--lipid conjugates regulate the calcium-induced fusion of liposomes composed of phosphatidylethanolamine and phosphatidylserine.

The effect of poly(ethylene glycol)--lipid (PEG--lipid) conjugates on liposomal fusion was investigated. Incorporation of PEG--lipids into large unilamellar vesicles (LUVs) composed of equimolar phosphatidylethanolamine (PE) and phosphatidylserine (PS) inhibited calcium-induced fusion. The degree of inhibition increased with increasing molar ratio of the PEG conjugate and with increasing size of the PEG moiety. Inhibition appeared to result from the steric barrier on the surface of the liposomes which opposed apposition of bilayers and interbilayer contact. In the presence of a large excess of neutral acceptor liposomes, however, fusogenic activity was restored. The rate of fusion under these conditions depended on the initial molar ratio of the PEG conjugate in the PE:PS vesicles and the length and degree of saturation of the acyl chains which composed the lipid anchor. These results are consistent with spontaneous transfer of the PEG--lipid from PE:PS LUVs to the neutral lipid sink reducing the steric barrier and allowing fusion of the PE:PS LUVs. The primary determinant of the rate of fusion was the rate of transfer of the PEG--lipid, indicating that liposomal fusion could be programmed by incorporation of appropriate PEG--lipid conjugates. Interestingly, increasing the size of the PEG group did not appear to affect the rate of fusion. The implications of these results with respect to the design of fusogenic liposomal drug delivery systems are discussed.

Calcium↗

PubMed1996

Modulation of vascular calcium channel activity in response to acute volume expansion in rats.

The mechanisms of the increased resistance in hypertension are still unclear. Several studies have indicated that the potential-sensitive Ca2+ channels (PSC) are altered in arteries isolated from hypertensive patients or animals. An expansion of body fluid volume may trigger local autoregulatory responses or may induce the release of humoral factors, either of which could increase systemic vascular resistance and cause volume-dependent forms of hypertension. We tested the hypothesis that volume expansion per se may cause the alterations of PSC similar to those seen in hypertension. For this, we examined the alterations of PSC in aortas from volume-expanded rats with the use of dihydropyridine-type Ca2+ channel activator, BayK 8644, in parallel with the changes in endothelium-dependent relaxation. Volume expansion was produced by a rapid intravenous infusion of saline (10% of body weight) over 30 min in rats. At the end of infusion, rats were killed and aorta removed for in vitro measurement of isometric tension. Relaxation to acetylcholine (10(-7)-10(-5) mol/L, % relaxation to 10(-7) mmol/L norepinephrine contraction) was not significantly changed. In contrast, contractile response to BayK 8644 (10(-9)-10(-6) mol/L, % response to 50 mmol/L KCl) was significantly enhanced in rats with volume expansion (12 control rats: 11.6 +/- 4.9%; 18 volume-expanded rats: 40.9 +/- 10.4% at 10(-6) mol/L, p < 0.05). These findings suggest that acute volume expansion could induce a similar enhanced vascular Ca2+ channel activity to that seen in hypertension in rats.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1996

Role of ouabain-like compound in the regulation of plasma aldosterone concentration in rats.

A major biologically active Na,K-ATPase inhibitor in the mammalian circulation may be ouabain-like compound(OLC). We developed a population of immunized rats against ouabain to block the actions of circulating OLC. To investigate the roles of OLC in the regulation of aldosterone secretion and/or production, we measured plasma aldosterone concentration after a week of low salt diet. No significant changes in serum Na and K concentrations were observed in immune rats. The plasma aldosterone concentration was significantly decreased by 30% in 17 immune rats as compared with 11 control rats(control: 455 +/- 53, immune: 315 +/- 21 pg/mL, p < 0.05). These data indicate that chronic blockade of the circulating OLC significantly decreases plasma aldosterone concentration during salt depletion and suggest that endogenous OLC may play an important role in the regulation of aldosterone secretion and/or production.

Aldosterone↗

PubMed1996

Developmental expression of the Bombyx Antennapedia homologue and homeotic changes in the Nc mutant.

BACKGROUND: Abundant availability of homeotic mutants in Bombyx mori provides us with clues to study the body plan of the silkworm. Previous studies indicated that the ECa/ECa and EN/EN embryos, which reveal drastic morphological changes (Itikawa 1943, 1952) lack the homologue of abd-A and the homologues of abd-A and Ubx, respectively (Ueno et al. 1992). It will be interesting to characterize a mutant named Nc, the locus of which was mapped about 1.4 cm apart from the E loci (Itikawa 1944, 1952). RESULTS: In the present study we cloned and identified the Bombyx Antennapedia cDNA from a library of larval middle silk gland. The developmental expression patterns of the Bombyx Antennapedia were analysed in embryos and larval middle silk glands. We found the Bombyx Antennapedia mRNA of the Nc mutant lacks the homeobox region and its downstream region. This defect comes from a corresponding deletion on the Nc chromosome. Development of the Nc/Nc embryos terminates at stage 26, revealing a transformation of the prothoracic legs into antennae, milder changes in the mesothoracic legs, compression between the prothoracic and mesothoracic segments as well as in the gnathocephalon region, and a severe growth suppression of the silk glands. CONCLUSIONS: These results give a molecular basis and detailed morphological abnormalities of the Nc mutant known since 1944.

Amino Acid Sequence↗

PubMed1996

Protective effects of ME3221 on hypertensive complications and lifespan in salt-loaded stroke-prone spontaneously hypertensive rats.

1. A comparison was made on the protective effects of the following: ME3221, a competitive angiotensin AT1 receptor antagonist; losartan, in which a major active metabolite is a non-competitive angiotensin AT1 receptor antagonist; and enalapril, an angiotensin-converting enzyme inhibitor, using the salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP received orally ME3221 (3 and 10 mg/kg per day), losartan (10 mg/kg per day) and enalapril (10 mg/kg per day) from the 6th to the 20th week of age. All the control rats showed rapid elevation of systolic blood pressure (SBP), accompanied by hypertensive complications, and died by 15 weeks of age. 3. ME3221, losartan and enalapril suppressed the elevation of SBP in the salt-loaded SHRSP to a comparable degree. ME3221 and losartan increased the survival rate to > 90%, and diminished hypertensive complications such as cerebral apoplexy (stroke), renal injury (increased proteinuria, and total N-acetyl-beta-D-glucosaminidase activity) and heart failure (cardiac hypertrophy and pleural effusion). 4. Competitive (ME3221) and non-competitive (losartan) angiotensin AT1 receptor antagonists showed comparable efficacy against the complications and mortality of the salt-loaded SHRSP; both were more potent than enalapril in the protective effect.

Angiotensin Receptor Antagonists↗

PubMed1996

ME3221, a surmountable angiotensin AT1-receptor antagonist, prevents hypertensive complications in aged stroke-prone spontaneously hypertensive rats.

The protective effects of ME3221, 3-methoxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-y l]methoxy] pyridine, on aged (32-week-old) stroke-prone spontaneously hypertensive rats (SHRSP) were studied following long-term (for 8 months) oral administration. At a dose of 10 mg/kg/day, ME3221 suppressed the mortality and the hypertensive complications observed in control SHRSP: cerebral apoplexy (hemorrhage, and spongeform and malacia in the cerebral cortex), increased proteinuria, and total N-acetyl-beta-D-glucosaminidase activity, and cardiac hypertrophy and pleural effusion. The protective activity of ME3221, a surmountable angiotensin AT1-receptor antagonist, was comparable to losartan, an insurmountable AT1-antagonist, and also to enalapril, an angiotensin-converting enzyme inhibitor. In addition, ME3221 reduced the systolic blood pressure more effectively than the two reference drugs.

Angiotensin Receptor Antagonists↗

PubMed1995

Pharmacological profile of ME3221, a novel angiotensin II receptor antagonist.

The pharmacological profile of a new surmountable angiotensin AT1 receptor antagonist, ME3221, 3-methoxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4- yl]methoxy]pyridine, was studied in several animal models, and was compared with that of losartan. EF2831, 3-hydroxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4- yl]methoxy]pyridine, a metabolite of ME3221, is also a surmountable angiotensin AT1 receptor antagonist, whose potency was 1/30 that of ME3221 in vitro, but equal to or 1/3 of that of ME3221 in in vivo experiments. In rats and marmosets, ME3221 antagonized angiotensin II-induced pressor responses, but did not affect bradykinin-induced depressor responses. ME3221 lowered the blood pressure in renal hypertensive rats and spontaneously hypertensive rats (SHR), and its ED25 value was 3 times that of losartan. Repeated administration of ME3221 to SHR had a stable and long-lasting antihypertensive effect without influencing heart rate. Thus ME3221, like losartan, may be useful in the treatment of renal and essential hypertension.

Angiotensin II↗

PubMed1995

Effect of chronic treatment with ME3221 on blood pressure and mortality in aged stroke-prone spontaneously hypertensive rats.

1. The protective effect of ME3221, a surmountable AT1 antagonist, on the hypertension and its concomitant complications in aged (32 week old) stroke-prone spontaneously hypertensive rats (SHRSP) was studied following long-term (32 weeks) oral administration, and compared with those of losartan (metabolite EXP3174 is an insurmountable AT1 antagonist) and enalapril. 2. During the treatment period, ME3221, at a dose of 10 mg/kg per day steadily reduced the systolic blood pressure, and no tolerance was developed to the fall in blood pressure. The reference drugs showed similar activity, but the antihypertensive effect of ME3221 was more potent. 3. In the control group, rats began to die from 52 weeks of age and all rats had died by 64 weeks of age. In contrast, no rats treated with ME3221, losartan or enalapril died before 64 weeks of age. 4. ME3221, losartan and enalapril suppressed the hypertensive complications observed in control SHRSP, that is, cerebral apoplexy (stroke and cerebral oedema), renal injury (increased proteinuria, total N-acetyl-beta-D-glucosaminidase activity and ascites) and heart failure (cardiac hypertrophy and pleural effusion). 5. These results indicate that ME3221 has a stable anti-hypertensive effect, prevents hypertensive complications and prolongs survival in aged SHRSP equally as well as losartan and enalapril.

Aging↗

PubMed1995

Effects of intracerebroventricular infusion of Fab fragments of digoxin antibody (Digibind) on development of reduced renal mass-saline hypertension in rats.

To clarify the role of brain ouabain-like compound in reduced renal mass-saline hypertension, we examined the effects of intracerebroventricular infusion of the Fab fragments of antidigoxin antibody (Digibind) on the change in blood pressure of saline-drinking subtotally nephrectomized rats. Twenty male Wistar rats weighing 250 g each underwent subtotal nephrectomy. Two groups of 10 rats received intracerebroventricular infusion of Digibind (20 mg/ml) or normal sheep IgG (20 mg/ml) at a rate of 0.5 microliters/h for 11 days. All rats began to drink 1% NaCl solution after two days of infusion. Systolic blood pressure was measured by the tail-cuff method on days 2, 6 and 9 of infusion. Two groups of saline-drinking rats with reduced renal mass developed hypertension. However, systolic blood pressure was significantly higher in Digibind-infused rats than in IgG-infused rats (day 2, 144 +/- 3(SEM) vs. 133 +/- 1 mmHg, p < 0.05; day 6, 161 +/- 4 vs. 151 +/- 2 mmHg, 0.05 < p < 0.1, day 9, 181 +/- 8 vs. 155 +/- 2 mmHg, p < 0.05). In spite of similar renal dysfunction, plasma aldosterone concentrations, and plasma OLC levels, the accelerated increase in blood pressure was accompanied by a significantly impaired pressure-natriuresis relationship (0.089 +/- 0.013 vs. 0.131 +/- 0.013 mmol/day/mmHg, p < 0.05). These results indicate that chronic intracerebroventricular infusion of Digibind augmented reduced renal mass-saline hypertension in rats and suggest that brain ouabain-like compound may play a protective role against the elevation of blood pressure, at least in this model of hypertension.

Animals↗

PubMed1995

Time pressure, type A syndrome, and organizational citizenship behavior: a field study replication of Hui, Organ, and Crooker (1994)

A field study of 182 university students in their residences tested the relationships among subjective time pressure, Type A scores, and organizational citizenship behavior. Perceived time pressure did not inhibit any form of citizenship behavior. Scores on the Achievement-Striving dimension of the Type A measure were positively related to the impersonal form of citizenship behavior as well as perceived time pressure and grade point average.

Adult↗

PubMed1994

Role of ouabainlike compound in rats with reduced renal mass-saline hypertension.

Ouabainlike compound (OLC) has recently been identified as a likely mammalian endogenous digitalis-like factor (EDLF) from human plasma. In this study, plasma levels of OLC were determined to assess the role of OLC in a model known as volume-expanded, reduced renal mass (RRM)-saline (S) hypertension in rats with use of a newly developed radioimmunoassay for ouabain. In the first experiment, at 3 wk after subtotal nephrectomy and drinking 1% saline solution, sysolic blood pressure (SBP) of 18 rats with reduced renal mass (RRM-S rats) was significantly higher than in 17 sham-operated saline-drinking control (C-S) rats [154 +/- 4 (SE) vs. 132 +/- 2 mmHg; P < 0.01]. Plasma OLC levels were 355 +/- 68 pmol/l in RRM-S rats, sevenfold higher than in C-S rats (54 +/- 4 pmol/l; P < 0.01). In the second experiment, we measured plasma OLC levels of 10 RRM-S, 12 sham-operated control (C), and 10 subtotally nephrectomized rats drinking distilled water (RRM rats). Concomitant with a marked increase in blood pressure (203 +/- 5 mmHg), RRM-S rats showed significantly higher plasma OLC levels compared with C and RRM rats (RRM-S 114 +/- 24, C 47 +/- 11, and RRM 52 +/- 9 pmol/l; P < 0.05). In both experiments, plasma OLC levels correlated significantly with SBP (P < 0.05). These findings suggest that plasma OLC shows a similar behavior to that of EDLFs or Na(+)-K(+)-adenosinetriphosphatase inhibitors reported in previous publications and may play a role in hypertensive mechanisms in rats with RRM and excess Na intake.

Animals↗

PubMed1994

Participation of ouabainlike compound in reduced renal mass-saline hypertension.

We examined the role of ouabainlike compound in reduced renal mass-saline hypertension using a population of rats immunized with ouabain. To develop ouabain-immunized rats, ouabain-bovine serum albumin conjugates were injected subcutaneously three times at 4-week intervals. Titer determinations were made 2 weeks after the third immunization, and rats with high titers were used in the study. Immunoglobulin G fractions from ouabain-immunized rats effectively inhibited the contractile response of guinea pig aorta to exogenous ouabain (150 nmol). Fourteen ouabain-immunized and seven nonimmunized control rats underwent subtotal nephrectomy. An additional eight ouabain-immunized and six nonimmunized rats served as sham-operated rats. Four groups of rats drank 1% NaCl solution for 3 weeks, and systolic blood pressure was measured weekly by the tail-cuff method. Two groups of sham-operated rats remained normotensive. In contrast, two groups of subtotally nephrectomized rats developed hypertension. However, among these rats, systolic blood pressure was significantly lower in ouabain-immunized rats than in nonimmunized rats (161 +/- 5 versus 180 +/- 3 [+/- SEM) mm Hg, P < .01). The decrease in blood pressure was accompanied by a significant inhibition of aortic hypertrophy (P < .05). These results indicate that chronic blockade of circulating ouabainlike compound partly ameliorates reduced renal mass-saline hypertension and suggest that circulating ouabainlike compound may be involved in the pathophysiology in this model of hypertension.

Adrenal Glands↗

PubMed1994

Role of brain ouabainlike compound in central nervous system-mediated natriuresis in rats.

Intracerebroventricular infusion of artificial sodium-rich cerebrospinal fluid induces increases in blood pressure and urinary sodium excretion. To examine the role of brain ouabainlike compound in these central nervous system-mediated responses, we evaluated the effects of prior intracerebroventricular injection of the Fab fragments of digoxin-specific antibody (Digibind, 10 mg/mL, 10 microL) on changes in blood pressure and urinary sodium excretion after intracerebroventricular infusion of high-sodium (323 mmol/L, 150 microL/kg per 15 minutes) cerebrospinal fluid in anesthetized rats. Antiouabain action of Digibind was revealed by the inhibition of a contractile response to ouabain in guinea pig aorta. Similar significant increases in blood pressure were found in rats that received preinjection of Digibind (n = 14) compared with control rats that received injection of saline (n = 5) or normal sheep IgG (n = 8). In rats pretreated with Digibind the natriuretic responses to central high sodium were significantly diminished by 68% (P < .05) or 82% (P < .05) compared with rats treated with saline or normal IgG, respectively. In contrast, Digibind did not affect either pressor or natriuretic responses to intracerebroventricular angiotensin II (600 ng/30 microL per 10 minutes). These data indicate that Digibind significantly inhibits increases in renal sodium excretion in response to high central sodium and suggest that brain ouabainlike compound may be involved in central nervous system-mediated natriuresis with nonpressor mechanisms.

Animals↗

PubMed1994

Expression of mouse LSP1/S37 isoforms. S37 is expressed in embryonic mesenchymal cells.

Mouse LSP1 is a 330 amino acid intracellular F-actin binding protein expressed in lymphocytes and macrophages but not in non-hematopoietic tissues. A 328 amino acid LSP1-related protein, designated S37, is expressed in murine bone marrow stromal cells, in fibroblasts, and in a myocyte cell line. The two proteins differ only at their N termini, the first 23 amino acid residues of LSP1 being replaced by 21 different residues in S37. The presence of different amino termini suggests that the LSP1 and S37 proteins are encoded by transcripts arising through alternative exon splicing. Here we report the genomic organization of the Lsp1 gene and show that the distinct N termini of LSP1 and S37 are encoded by two alternatively used exons, each containing a translational start codon. We also demonstrate that alternative 3' acceptor sites are used in the splicing of exon 5. This results in LSP1 and S37 transcripts that either do or do not contain 18 bp encoding the 6 amino acids HLIRHQ of the acidic domain. Therefore, the Lsp1 gene encodes four protein isoforms: full-length LSP1 and S37 proteins, designated LSP1-I and S37-I and the same proteins without the HLIRHQ sequence, designated LSP1-II and S37-II. By in situ hybridization analysis we show that the S37 isoforms are expressed in mesenchymal tissue, but not in adjacent epithelial tissue, of several developing organs during mouse embryogenesis. This, together with our finding that S37 is an F-actin binding protein, suggests that S37 is a cytoskeletal protein of mesenchymal cells, which may play a role in mesenchyme-induced epithelial differentiation during organogenesis.

Actins↗

PubMed1994

Time pressure, type A syndrome, and organizational citizenship behavior: a laboratory experiment.

Time pressure was manipulated in a laboratory task for 77 undergraduate subjects, who also responded to a measure of Type A syndrome. Afterwards, an occasion for organizational citizenship behavior was presented in the form of participation in a survey. Type A scores were unrelated to those on any measure of organizational citizenship behavior; time pressure acted to depress especially the quality of organizational citizenship behavior.

Adult↗

PubMed1993

Digitalis-like factors from human urine.

We isolated two candidates for endogenous digitalis-like factors from human urine based on the inhibition of [3H]ouabain binding to intact human erythrocytes. The more-polar ouabain-displacing compound-1 (ODC-1) closely resembled ouabain in biological, physicochemical, and chromatographic properties. Moreover, anti-ouabain IgG dose-dependently neutralized the action of ODC-1. The less-polar ODC-2 behaved identically to digoxin in three analytical high-performance liquid chromatography and thin layer chromatography systems. Fast atom bombardment mass spectrum and proton nuclear magnetic resonance spectrum supported the notion that ODC-2 may be indistinguishable from digoxin. The possibility that substances quite similar to cardenolides are synthesized in the mammalian body must be seriously considered.

Binding Sites↗