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Biomedical subjects

H Yu

Publications and source records attributed to H Yu.

At least 109 records · Page 6Linked to original sources
PubMed1997

Molecular requirements for bi-directional movement of phagosomes along microtubules.

Microtubules facilitate the maturation of phagosomes by favoring their interactions with endocytic compartments. Here, we show that phagosomes move within cells along tracks of several microns centrifugally and centripetally in a pH- and microtubule-dependent manner. Phagosome movement was reconstituted in vitro and required energy, cytosol and membrane proteins of this organelle. The activity or presence of these phagosome proteins was regulated as the organelle matured, with "late" phagosomes moving threefold more frequently than "early" ones. The majority of moving phagosomes were minus-end directed; the remainder moved towards microtubule plus-ends and a small subset moved bi-directionally. Minus-end movement showed pharmacological characteristics expected for dyneins, was inhibited by immunodepletion of cytoplasmic dynein and could be restored by addition of cytoplasmic dynein. Plus-end movement displayed pharmacological properties of kinesin, was inhibited partially by immunodepletion of kinesin and fully by addition of an anti-kinesin IgG. Immunodepletion of dynactin, a dynein-activating complex, inhibited only minus-end directed motility. Evidence is provided for a dynactin-associated kinase required for dynein-mediated vesicle transport. Movement in both directions was inhibited by peptide fragments from kinectin (a putative kinesin membrane receptor), derived from the region to which a motility-blocking antibody binds. Polypeptide subunits from these microtubule-based motility factors were detected on phagosomes by immunoblotting or immunoelectron microscopy. This is the first study using a single in vitro system that describes the roles played by kinesin, kinectin, cytoplasmic dynein, and dynactin in the microtubule-mediated movement of a purified membrane organelle.

Adenosine Triphosphate↗
PubMed1997

Psychometric properties of the Eating Disorders Inventory (EDI-1) in a nonclinical Chinese population in Hong Kong.

OBJECTIVES: To evaluate the psychometric properties of the Chinese Eating Disorders Inventory (EDI-1) in a nonclinical population in Hong Kong. METHOD: 1,172 (females 606, males 566) Chinese undergraduates completed the Chinese EDI-1; 105 of them also completed the 12-item General Health Questionnaire (GHQ-12). RESULTS: In female subjects, the Chinese EDI-1 and its subscales met conventional standards of internal consistency, item-total, item-subscale, and subscale correlations, and exhibited an excellent degree of factorial integrity. The subscales discriminated among male, female, high Drive for Thinness, high Body Dissatisfaction, constitutionally slim, and Canadian female subjects. Female GHQ-12 cases and noncases were only distinguished by the Interpersonal Distrust, Interoceptive Awareness, and Ineffectiveness subscales. 3.3% of female subjects could be characterized as being pathologically weight preoccupied. DISCUSSION: This study provides preliminary evidence that the Chinese EDI-1 is an economical, reliable, and potentially useful self-report instrument for investigating the psychological and behavioral dimensions of eating disorders in Hong Kong. But further work is needed to evaluate its transcultural validity in clinical and less modernized Chinese populations.

Adolescent↗
PubMed1997

Oral absorption of anti-aids nucleoside analogues: 3. Regional absorption and in vivo permeability of 2',3'-dideoxyinosine in an intestinal-vascular access port (IVAP) dog model.

The absolute oral and regional intestinal bioavailabilities (BAs) and pharmacokinetics (PK) of 2',3'-dideoxyinosine (ddI), a nucleoside analog used in the treatment of human immunodeficiency virus (HIV) infection, were investigated in an in vivo intestinal-vascular access port (IVAP) dog model. The mean (+/- SD) absolute regional intestinal BAs of ddI were 49.6 +/- 8.8, 42.7 +/- 7.9, and 13.6 +/- 5.4% after the bolus administration of unbuffered solutions containing 250 mg ddI into the duodenum, ileum, and colon of IVAP beagle dogs, respectively. The BA of the orally administered Videx 250 mg buffered chewable tablets was 44.9 +/- 1.6%. ddI absorption and disposition PK were modeled by simultaneously fitting intravenous, oral, and intestinal plasma level versus time data using a physiologically based PK model. The region-specific apparent absorption rates followed the rank order duodenum > ileum > colon. Apparent regional in vivo intestinal permeabilities correlated well with previously determined regional permeabilities in rats. The intestinal pH was monitored using a radiotelemetric pH monitoring system since ddI is unstable in an acidic environment. While the pH was found to be lower in the duodenum and proximal jejunum (approximately pH 6) than in the ileum or colon (pH > or = 7.0), ddI is reasonably stable across the entire pH range of the dog small intestine. These studies demonstrate that the regional reduction in ddI BA is consistent with a reported distal reduction in intestinal permeability and appears to be a significant contributing factor to the high degree of absorption variability reported for ddI.

Administration, Oral↗
PubMed1997

Use of single-cycle analysis to study rates and mechanisms of retroviral mutation.

Retroviruses evolve at rapid rates. This allows them to escape immune surveillance, thwarts vaccine development, and leads to rapid emergence of drug-resistant virus. Information regarding the retroviral mutation rates and the underlying mechanisms of mutagenesis will undoubtedly expedite the development of strategies to combat retroviral-mediated diseases. In this review, we discuss how the unique retroviral life cycle can be adapted such that retroviral variation can be studied in a single cycle of replication. By limiting replication to a single cycle, retroviral mutation rates can be directly measured, and the consequences of mutations can be observed. In addition, retroviral recombination rates as well as the nature of primer strand transfer during reverse transcription can be studied using this system. Molecular analysis of the spectrum of mutations arising during a single cycle of virus replication also sheds light on the mechanisms of mutagenesis and retroviral replication.

Animals↗
PubMed1997

Developmental change in the voltage-dependence of the pacemaker current, if, in rat ventricle cells.

Myocytes were isolated from newborn and adult rat ventricle. Using the whole-cell patch clamp, the two cell populations were compared for the presence of the hyperpolarization-activated pacemaker current if. As in other mammalian species, the threshold voltage in acutely dissociated adult rat myocytes was extremely negative (-113 +/- 5 mV; n=12). In contrast, threshold in newborn cells was relatively positive, regardless of whether measured in acutely dissociated (-72 +/- 2 mV; n=6) or cultured cells (-70 +/- 2 mV; n=9). Current density was not reduced in the adult. These results suggest that with development the ventricle assumes its non-pacemaker function, at least in part, by a shift of the voltage dependence of if outside the physiological range.

Animals↗
PubMed1997

Nitric oxide stimulates prostaglandin synthesis in cultured rabbit gastric cells.

Both prostaglandins (PGs) and nitric oxide (NO) have cytoprotective and hyperemic effects in the stomach. However, the effect of NO on PG synthesis in gastric mucosal cells is unclear. We examined whether sodium nitroprusside (SNP), a releaser of NO, stimulates PG synthesis in cultured rabbit gastric mucus-producing cells. These cells did not release NO themselves. Co-incubation with SNP (2 x 10(-4), 5 x 10(-4), 10(-3) M) increased PGE2 synthesis, and SNP (10(-3) M) increased PGI2 synthesis in these cells. Hemoglobin, a scavenger of NO, (10(-5) M) eliminated the increase in PGE2 synthesis by SNP, but methylene blue, an inhibitor of soluble guanylate cyclase, (5 x 10(-5) M) did not affect the increase in PGE2 synthesis by SNP. 8-bromo guanosine 3':5'-cyclic monophosphate (8-bromo cGMP), a cGMP analogue, (10(-6), 10(-5), 10(-4), 10(-3) M) did not affect PGE2 synthesis. These findings suggest that NO increased PGE2 and PGI2 synthesis via a cGMP-independent pathway in cultured rabbit gastric cells.

Animals↗
PubMed1997

Effect of mifepristone and antiestrogens on uterine PGF2 alpha and PGE2 concentrations in ovariectomized and pregnant rats.

Four antiestrogens (anordiol, tamoxifen, RU 39411, ICI 182780) and the antiprogestin, mifepristone (RU 486), were administered to the following three animal models: (1) ovariectomized rats, (2) mated rats treated post-coitally; and (3) pregnant rats treated post-implantation. The antiestrogens were administered alone or in combination with mifepristone at doses effective in preventing and/or terminating pregnancy in rats. The objective of the study was to determine whether these drugs influenced uterine concentrations of prostaglandins (PGF2 alpha and PGE2). Antiestrogens administered alone to ovariectomized rats did not effect uterine PGE2 or PGF2 alpha concentrations; whereas the combination of anordiol/mifepristone increased uterine PGF2 alpha concentration, resulting in an increase in the PGF2 alpha/PGE2 ratio. Mated rats were treated post-coitally for three consecutive days with anordiol, tamoxifen, estradiol and mifepristone alone and with the combination of anordiol/mifepristone and tamoxifen/mifepristone. An increase in uterine PGF2 alpha concentrations and in the PGF2 alpha/PGF2 ratio occurred only in anordiol/mifepristone treated group. A decrease in uterine PGE2 concentrations occurred in animals treated with anordiol, tamoxifen and estradiol, resulting in an increase in the PGF2 alpha/PGE2 ratio. Anordiol (5.0 mg/kg/day) and mifepristone (4.0 mg/kg/day) alone and the combination of anordiol/mifepristone (2.5/1.0 mg/kg/day) administered to pregnant rats on day 7, 8 and 9 of pregnancy induced an increase in PGF2 alpha levels without affecting uterine PGE2 concentration. The changes in PGF2 alpha concentrations induced by anordiol and the combination of anordiol/mifepristone resulted in an increase in the PGF2 alpha/PGE2 ratio. The antiestrogens tested except for ICI 182780 possessed agonist activity when assayed by measuring their capacity to increase the uterine weights in ovariectomized rats. Also, ICI 182789 was the only antiestrogen that did not influence uterine PG concentrations. It can be concluded that ICI 182780 is the only "pure" antiestrogen among those tested. The present results show that antiestrogens and the combination of mifepristone plus anordiol at doses preventing implantation and terminating pregnancy increase uterine PGF2 alpha and/or decrease PGE2 concentrations, resulting in an alteration of PGF2 alpha/PGE2 ratio. These findings suggest that there exists a critical balance of PGF2 alpha to PGE2 concentrations in the uterus required for the normal passage of fertilized ova through the oviduct, initiating implantation of the blastocysts, development of embryos, and maintenance of pregnancy.

Abortifacient Agents, Steroidal↗
PubMed1997

Nonprostatic sources of prostate-specific antigen.

The name prostate-specific antigen has been given to a protein that now is known not to be prostate-specific; however, prostatic tissue does produces extremely high levels of PSA and secrets it into the seminal plasma. Seminal plasma contains about 1 million micrograms/L of PSA and is the richest source of PSA reported. The biologic fluid with the second highest PSA concentration, however, is nipple aspirate fluid from the female breast (up to about 5000 micrograms/L), and the third is milk from lactating women (up to 300 micrograms/L). Male serum PSA is usually less than 4 micrograms/L. In nonprostatic tissues, PSA exists mainly in its free molecular form, but PSA-ACT complex is also present in most of the fluids that contain PSA, such as breast secretions and amniotic fluid. The gene expression and protein production of PSA in nonprostatic tissues are under the regulation of steroid hormones via their receptors. Androgens, glucocorticoids, and progestins up-regulate the PSA gene expression, resulting in an increase of protein production. Estrogen by itself seems to have no effect on PSA regulation, but it can impair PSA production induced by androgen. It remains unknown whether PSA is enzymatically active and what is the physiologic role of PSA in nonprostatic tissues. It is speculated that PSA may be involved in the regulation of growth factors. Measuring PSA in breast cancer cytosol, breast-nipple aspirate fluid, and female serum may have potential clinical utilities, including breast cancer prognosis, breast cancer risk assessment, and evaluation of androgen excess. Further studies are needed to identify the exact function and regulation of PSA in nonprostatic tissues and to explore the clinical application of this protein.

Amniotic Fluid↗
PubMed1997

Composition of cartilagenous tissue with mineralized and non-mineralized zones formed in vitro.

We have previously shown that cartilagenous tissue with both non-mineralized and mineralized zones can be formed by chondrocytes which have been selectively isolated from the deep zone of bovine articular cartilage. In this study, we quantitate proteoglycan and collagen content, calcification, tissue thickness and cellularity over a 10 week culture period in order to study matrix accumulation and tissue formation. The cartilagenous tissue cellularity and proteoglycan and collagen accumulation continued up to 8 weeks and this was paralleled by an increase in tissue thickness. The amount of mineral in the tissue as well as the amount of collagen, in contrast to proteoglycan, was still increasing at 10 weeks. At the end of week 10, the amount of glycosaminoglycan and collagen as a percentage of dry weight of the tissue were 11.0 +/- 0.6% and 14.8 +/- 0.1%, respectively, compared with 10.5 +/- 1.2% and 35.1 +/- 5.8% for the in vitro deep articular cartilage. The amount of calcium as a percentage of dry weight of the cartilagenous tissue was 8.1 +/- 0.7% which was similar to the in vivo cartilage (9.1 +/- 1.6%). This data suggests that 8 weeks of culture may be necessary before the cartilagenous tissue is suitable for use as a transplant.

Animals↗
PubMed1997

A cytidine deaminase expressed in the post-infective L3 stage of the filarial nematode, Brugia pahangi, has a novel RNA-binding activity.

A number of genes have been identified that are highly expressed in the post-infective L3 stage of the filarial parasite, Brugia pahangi. Amongst these was a cDNA with homology to the cytidine deaminase (CDD) gene family. Phylogenetic analysis of the various cytosine nucleoside deaminases suggest that Brugia pahangi CDD evolved with significant divergence from the RNA editing family. In order to characterize its function, we have expressed Brugia pahangi CDD in bacteria as a chimera with maltose-binding protein (MBP). Biochemical analysis demonstrates the MBP-CDD fusion protein functions as an authentic cytidine deaminase with an obligate requirement for zinc. In addition to cytidine deaminase activity, however, the fusion protein demonstrates RNA binding activity with specificity for AU-rich sequences and was found to bind an RNA template spanning the edited site of mammalian apolipoprotein B (apoB) mRNA. This RNA binding activity was not found in two different recombinant bacterial CDD proteins. In vitro RNA editing assays revealed that MBP-CDD failed to mediate cytidine deamination of a mammalian apoB RNA template. Furthermore, binding of MBP-CDD to the apoB RNA did not inhibit in vitro editing of this template by apobec-1. The data suggest that the cytosine nucleoside deaminases and RNA editing deaminases have acquired different mechanisms of binding to an AU-rich RNA template, presumably with different functional implications.

Amino Acid Sequence↗
PubMed1997

Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues.

Growth hormone release is under tight control by two hypothalamic hormones: growth hormone-releasing hormone and somatostatin. In addition, synthetic growth hormone secretagogues have also been shown to regulate growth hormone release through the growth hormone secretagogue receptor (GHS-R), suggesting the existence of an additional physiological regulator for growth hormone release. To understand the physiological role of the GHS-R in more detail, we mapped the expression of mRNA for the receptor by in situ hybridization and RNase protection assays using rat and human tissues. In the rat brain, the major signals were detected in multiple hypothalamic nuclei as well as in the pituitary gland. Intense signals were also observed in the dentate gyrus of the hippocampal formation. Other brain areas that displayed localized and discrete signals for the receptor include the CA2 and CA3 regions of the hippocampus, the substantia nigra, ventral tegmental area, and dorsal and median raphe nuclei. In resemblance to the results from rat brain, RNase protection assays using human tissues revealed specific signals in pituitary, hypothalamus and hippocampus. Moreover, a weak signal was noted in the pancreas. The demonstration of hypothalamic and pituitary localization of the GHS-R is consistent with its role in regulating growth hormone release. The expression of the receptor in other central and peripheral regions may implicate its involvement in additional as yet undefined physiological functions.

Animals↗
PubMed1997

Infant mortality among various nationalities in the middle part of Guizhou, China.

This paper describes infant mortality, leading causes of death, and some associated factors among the Han, the Miao, the Bouyei and other minority nationalities in three counties of the middle part of Guizhou Province, China. The results showed that the overall infant mortality rate (IMR) in these areas was 125.7 per 1000 live births during 1985-1987. There existed a great disparity in IMR among different nationalities. The rate was 103.1 (Han), 148.8 (Miao), 161.2 (Bouyei) and 145.0 (other ethnic groups) per 1000 live births, respectively. The five leading causes of death in infants were respiratory diseases, neonatal tetanus, birth asphyxia, infectious diseases and diarrhoea. These causes of death combined resulted in an IMR of 104.1 per 1000 live births. However, these diseases varied in importance for infants of different nationalities. We considered the relationship between infant death and maternal and child health care. The location of birth, the kinds of birth attendants and utilization of health facilities might be associated with differentials of infant mortality among these nationalities. Maternal education was associated with infant survival, but it might not be the only factor in decreasing or eliminating the differential of IMR among various nationalities. Based upon the findings, it is urgent to improve maternal and child health care and investigate further cultural and sociological factors among various nationalities.

Anthropology, Cultural↗
PubMed1997

Differential purinergic receptor signalling in osteoclasts and osteoblastic cells.

There are differences between osteoclasts and osteoblastic cells in their cytosolic calcium responses to purinergic receptor activation. Application of 50 or 100 microM extracellular ATP inhibits the calcium response to a second application of ATP in osteoblastic rat osteosarcoma UMR 106 cells, but not in rabbit osteoclasts. This shows that there is adaptation to the extracellular, ATP in osteoclasts, but not in the UMR 106 cells. Extracellular washing of the UMR 106 cells restores the calcium response to ATP partially but not completely, indicating that there is a purinergic receptor activation-induced desensitisation of the receptor or its linked signalling pathways. In contrast to these results, if extracellular UTP is applied first, application of ATP produces no calcium response in osteoclasts, with or without washing, while in the UMR 106 cells there is some response to the ATP, which is greatly enhanced by washing. This indicates that UTP induces a complete desensitisation of the purinergic receptor/calcium signalling system in osteoclasts, but not in the osteoblastic cells, in which there is simply competition between UTP and ATP for the same receptors. Taken together, these results demonstrate that ATP and UTP could differentially regulate osteoblasts and osteoclasts.

Adaptation, Physiological↗
PubMed1997

Pharmacokinetic and pharmacodynamic studies of (R)-8-hydroxy-2-(di-n-propylamino)tetralin in the rat.

Racemic 8-OH-DPAT, (R,S)-8-hydroxy-2-(di-n-propylamino)tetralin, has become the prototype 5-HT1A receptor agonist. The enantiomers of 8-OH-DPAT have similar affinities to the 5-HT1A receptor, but the (R)-enantiomer is a full agonist, whereas the (S)-enantiomer is a partial agonist. This communication describes the dose- and time-response relationships of behavioural (5-HT behavioural syndrome, cage-leaving response), physiological (body temperature) and biochemical (5-HT turnover, 5-hydroxytryptophan accumulation) effects of (R)-8-OH-DPAT in rats. A high-performance liquid chromatography (HPLC)-UV method for determination of plasma and brain concentrations of (R)-8-OH-DPAT was developed, permitting studies of the pharmacokinetics of the drug. The concentrations of 8-OH-DPAT in brain were several fold higher than in plasma, and there were large variations in (R)-8-OH-DPAT concentrations between brain regions (highest in the hippocampus). (R)-8-OH-DPAT peaked in plasma at 5 min and in brain at 15 min after subcutaneous administration. The 5-HT1A behavioural syndrome peaked within 5 min after administration and disappeared after 30 min, when brain concentrations were still high. The hypothermic and biochemical responses developed gradually and were maximal at 45-60 min post injection, when both plasma and brain concentrations were declining. Thus, there was not a simple relationship between the kinetics and the dynamics of (R)-8-OH-DPAT. These results prompt further studies on the pharmacokinetics of 8-OH-DPAT within the central nervous system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Influence of the microporous substratum and hydrodynamics on resistances to drug transport in cell culture systems: calculation of intrinsic transport parameters.

Although cell culture models are increasingly used to study drug transport and metabolism, the influence of the substratum on the transport properties of the cell monolayer has not been studied in great detail. Furthermore, the use of effective (or apparent) permeabilities (Peff) assumes that the contribution of the microporous filter substratum and the aqueous boundary layer (ABL) to transport are negligible or are at least constant for a series of drugs. In the present study, the permeabilities of the substratum, ABL, and monolayer were obtained for a series of compounds at variable flow rates in side-by-side diffusion chambers. Comparisons of transport properties were made between cell monolayers grown on substrata made of polycarbonate (PC) and polyester (PE). All paracellular markers demonstrated a reduction in permeability and a corresponding increase in transepithelial electrical resistance (TEER) through PE-grown monolayers. The permeabilities of two carrier-mediated compounds, phenylalanine and proline, were 55% higher and 48% lower through PE-grown monolayers than through the PC-grown monolayers, respectively. The resistance to progesterone transport attributed to the PE and PC filters was large (71% and 27% of total resistance, respectively) at a flow rate of 20 mL/min, indicating that the monolayer was not the rate-limiting transport barrier. Therefore, for highly permeable compounds, reporting Peff has limited value since it is an indicator of the transport properties of the substratum rather than of the monolayer. These results demonstrate that substratum properties (e.g., membrane composition, pore size, etc.) significantly affect the barrier properties of the Caco-2 cell monolayer. The most probable mechanism is by the modulation of the functional expression of nutrient and ion transporters resulting in variable transcellular and paracellular transport properties. These results further demonstrate the importance of calculating intrinsic membrane transport parameters if the monolayer is not maintained as the rate-determining barrier in the transport experiment. Using higher flow rates and higher porosity substrata supports may help maintain the monolayer as the rate-limiting transport barrier.

Biological Transport↗
PubMed1997

Evidence for diminished functional expression of intestinal transporters in Caco-2 cell monolayers at high passages.

PURPOSE: To investigate the effects of passaging on the intrinsic membrane transport parameters of compounds absorbed by means of passive and carrier-mediated processes in the Caco-2 cell line. METHODS: Caco-2 cells at low (28-36) and high (93-108) passage numbers were used to evaluate the transport characteristics of model compounds for paracellular diffusion (mannitol), transcellular diffusion (progesterone) and carrier-mediated transport (cephalexin, cephradine, phenylalanine, proline, and taurocholic acid) using side-by-side diffusion chambers. Intrinsic intestinal transport parameters were determined by correcting the effective permeability for potential biases introduced by the microporous filter and aqueous boundary layer. Intrinsic maximal flux (Jmax), Michaelis constant (K(m)) and carrier permeability (Pc) were determined as a function of passage number. RESULTS: Compared to the low passaged cells, the high passaged Caco-2 cells were characterized by less morphological heterogeneity, higher transepithelial electrical resistance, higher transcellular diffusion, lower paracellular diffusion, lower carrier-mediated transport and lower alkaline phosphatase activity. The use of effective transport parameters overestimated the K(m) and underestimated Pc but had no effect on Jmax. CONCLUSIONS: The current results provide experimental evidence that the passaging process significantly affects the biological characteristics and transport properties of Caco-2 cell monolayers. The effects are consistent with a reduction in the functional expression of a brush border enzyme and several transport proteins as passage number is increased. The underlying basis for this appears to be a selection of fast-growing subpopulations from the original heterogeneous Caco-2 cell line during passaging.

Alkaline Phosphatase↗
PubMed1997

Artificial neural network method for predicting the specificity of GalNAc-transferase.

The specificity of GalNAc-transferase is consistent with the existence of an extended site composed of nine subsites, denoted by R4, R3, R2, R1, R0, R1', R2', R3', and R4', where the acceptor at R0 is either Ser or Thr to which the reducing monosaccharide is anchored. To predict whether a peptide will react with the enzyme to form a Ser- or Thr-conjugated glycopeptide, a neural network method--Kohonen's self-organization model is proposed in this paper. Three hundred five oligopeptides are chosen for the training site, with another 30 oligopeptides for the test set. Because of its high correct prediction rate (26/30 = 86.7%) and stronger fault-tolerant ability, it is expected that the neural network method can be used as a technique for predicting O-glycosylation and designing effective inhibitors of GalNAc-transferase. It might also be useful for targeting drugs to specific sites in the body and for enzyme replacement therapy for the treatment of genetic disorders.

Glycosylation↗