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Biomedical subjects

J D Huang

Publications and source records attributed to J D Huang.

At least 19 recordsLinked to original sources
PubMed2006

Disruption of granules by hydrodynamic force in internal circulation anaerobic reactor.

A process of granule disruption by hydrodynamic force is discussed in this paper. Shear force and attrition among granules originated from hydrodynamic force are the main causes of the disruption. Since it is positively correlated to the attrition force, the shear force is utilized to describe the effect of hydrodynamic force on granule disruption. In the experiment, when increase rate of average shear rate (IRgamma) of the 1st stage is about 0.2 s(-1) x d(-1), the granules are disrupted; while re-granulation could develop when IRgamma is about 0.07 s(-1) x d(-1); even when the shear rate is as high as about 30s(-1), the granulation rate keeps stably at a relatively high level, which shows that granules could bear the high hydrodynamic force only if it increases by low increase rate. The experimental results would be valuable for the operation and controlling of the upflow reactors.

Aerobiosis↗
PubMed2001

Sex change in the protandrous black porgy, Acanthopagrus schlegeli: a review in gonadal development, estradiol, estrogen receptor, aromatase activity and gonadotropin.

Black porgy, Acanthopagrus schlegeli Bleeker, a marine protandrous hermaphrodite, is functional male for the first two years of life but begins to sexually change to female after the third year. Testicular tissue and ovarian tissue was separated by connective tissue in the bisexual gonad. This sex pattern provides a very good model to study the endocrine mechanism of sex change in fish. The annual profiles of plasma estradiol, vitellogenin and 11-ketotestosterone concentrations in males were significantly different from those in the three-year-old females. Significantly high levels of plasma estradiol during the prespawning/spawning season and low levels of plasma 11-ketotestosterone during the spawning season were observed in the inversing females. No difference of plasma testosterone levels was observed in males and females. Oral administration of estradiol stimulated high levels of gonadal aromatase activity, plasma gonadotropin II levels and sex change in the two-year-old fish. Exogenous estradiol administered for 5-6 months induced a reversible sex change in one- and two-year-old fish. The sensitive period for estradiol treatment of sex change is from early prespawning to spawning season. Implantation with testosterone for more than a year could not block the natural sex change in three-year-old fish. Exogenous aromatase inhibitors (1,4,6-androstatriene-3,17-dione or fadrozole) suppressed aromatase activity in the brain. Oral administration with aromatase inhibitors for a year further inhibited the natural sex change in three-year-old black porgy and all fish became functional male with spermiation. Estrogen receptor alpha gene in the ovarian tissue of bisexual gonad is significantly less expressed than that in the vitellogenic ovary of female on the basis of reverse-transcription polymerase-chain reaction. There was no difference in the annual profiles of the plasma gonadotropin II levels in the males and natural inversing females. Plasma gonadotropin II levels were significantly higher in estradiol-treated group than those in the control. It is concluded that estradiol, aromatase activity and estrogen receptor in the ovarian tissue play an important role in the natural and controlled sex change in black porgy. The association of gonadotropin and sex change in black porgy is not clear.

Administration, Oral↗
PubMed2001

Regulation of plasma gonadotropin II secretion by sex steroids, aromatase inhibitors, and antiestrogens in the protandrous black porgy, Acanthopagrus schlegeli Bleeker.

Plasma gonadotropin II (GTH II) concentrations were significantly higher (approx. 15-20-fold) in estradiol-17beta (E(2)) treated (1.0 microg or 2.5 microg g(-1) body weight) female black porgy from days 4 to 12 compared with the control. E(2) (1 microg g(-1) wt.) had a stronger stimulation on plasma GTH II in early recrudescent phase (low GSI) males (11-fold) than in high GSI and late spermiating males (2.6-fold, P< 0.05). No effect of androgens (testosterone, T; 5alpha-dihydrotestosterone, DHT) on plasma GTH II levels was observed either sex. The levels of plasma GTH II were stimulated in 1,4,6-androstatriene-3,17-dione (ATD, 1 microg g(-1), 2 microg g(-1) body wt.) and fadrozole-treated (1 microg g(-1), 3 microg g(-1) body wt.) groups compared to control. Tamoxifen (1 microg g(-1), 3 microg g(-1) body wt.) but not enclomiphene could stimulate high GTH II levels in plasma. In another experiment of ATD in combination with T, T treatment further attenuated the ATD stimulation of plasma GTH II levels. We concluded that GTH II secretion is positively regulated by an estrogen-specific effect in female and male black porgy. Gonadal stage had significant effects on the responsiveness of GTH II to E(2) stimulation in males. A negative aromatase-dependent feedback control of plasma GTH II levels was also suggested in the protandrous black porgy, Acanthopagrus schlegeli.

Animals↗
PubMed2001

Effect of hydroxyzine on the transport of etoposide in rat small intestine.

Etoposide, an anti-neoplastic agent and a substrate of P-glycoprotein (P-gp), exhibits variable oral bioavailability. P-gp, the multidrug resistance gene (mdr1) product, has been considered as an absorption barrier against intestinal drug absorption. Terfenadine, an antihistamine, has been shown to be a P-gp inhibitor. The current study was designed to assess the effect of hydroxyzine, an antihistamine, on the transport of etoposide in the small intestine. Everted rat gut sacs were used to determine the absorption and exsorption of etoposide under different conditions, as rhodamine 123 was chosen to evaluate the role of P-gp in the drug interaction. The results showed that the transport of etoposide was significantly increased from the luminal site to the serosal site in the jejunum by 2- and 4-fold after 90 min in the presence of hydroxyzine and quinidine, respectively. A similar trend was observed in the ileal sacs. This in vitro exsorption study also demonstrated that hydroxyzine could reduce the efflux of etoposide to the luminal site in either jejunum or ileum. The effect of hydroxyzine on the pharmacokinetics of etoposide differed by the in vivo route of administration, thus assuming clinical importance for chemotherapeutic treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Novel mutations of CYP3A4 in Chinese.

Human cytochrome P450 3A4 is a major P450 enzyme in the liver and gastrointestinal tract. It plays important roles in the metabolism of a wide variety of drugs, some endogenous steroids, and harmful environmental contaminants. CYP3A4 exhibits a remarkable interindividual activity variation as high as 20-fold. To investigate whether the interindividual variation in CYP3A4 levels can be partly explained by genetic polymorphism, we analyzed DNA samples from 102 Chinese subjects by polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis for novel point mutation in the CYP3A4 coding sequence and promoter region. Using PCR and directed sequencing method to establish the complete intron sequence of CYP3A4 from leukocytes, the complete genomic sequence from exon 1 through 13 of CYP3A4 was determined and published in the GenBank database (accession no. AF209389). CYP3A4-specific primers were designed accordingly. After PCR-single-strand conformation polymorphism and restriction fragment length polymorphism screening, we found three novel mutations; two are point mutations and one is insertion. The first variant allele (CYP3A4*4), an Ile118Val change, was found in 3 of 102 Chinese subjects. The next allele (CYP3A4*5), which causes a Pro218Arg amino acid change, was found in 2 of 102 subjects. We found an insertion in A(17776), designated as CYP3A4*6, which causes frame shift and an early stop codon in exon 9, in one heterozygous subject. We also investigated the CYP3A4 activity in these mutant subjects by measuring the morning spot urinary 6beta-hydroxycortisol to free cortisol ratio with the enzyme-linked immunosorbent assay method. When compared with healthy Chinese population data, the 6beta-hydroxycortisol to free cortisol ratio data suggested that these alleles (CYP3A4*4, CYP3A4*5, and CYP3A4*6) may decrease the CYP3A4 activity. Incidences of these mutations in Chinese subjects are rare. The prevalence of these point mutations in other ethnic groups and its effect on the metabolic activity of CYP3A4 remain to be further evaluated.

Alleles↗
PubMed2001

Genetic polymorphism of cytochrome P450 3A5 in Chinese.

The CYP3A subfamily enzymes are the most abundant and important drug-metabolizing enzymes. Wide variation in the CYP3A5 expression was well known. Recently, G(-44) to A of CYP3AP1 was found to segregate with CYP3A5*3 defective allele. The homozygous A(-44) subjects showed low expression of CYP3A5. In Caucasian, only 9.2% of CYP3AP1 alleles were with G(-44) and associated with the wild-type CYP3A5*1 allele, which expressed CYP3A5 significantly. By using polymerase chain reaction and FauI endonuclease digestion, we found that 28% of CYP3AP1 alleles are G(-44) in 110 Chinese subjects. The frequency is 3 times higher in Chinese than in Caucasian, implying more Chinese subjects are probably extensive CYP3A5 metabolizers. In two Chinese subjects, we also found a heterozygous G(13048)gt-to-G(13048)gc mutation at the intron 5 splicing donor site, leading to a splicing defect. A 6478-base pair minigene, including intron 4 to intron 7, was used for in vitro transcription. Both the wild-type and the mutated minigenes produced splicing variants. The wild-type minigene used Ggt(13050) as the splicing donor. The mutant minigene used gt(8504) in intron 4 or gt(13112) in intron 5 as the splicing donor for various splicing acceptors. The splicing defect may result in a shorter peptide or cause the frame shift. In the other two Chinese subjects, we found A(14763)-to-G mutation in exon 7, resulting in the Q200R amino acid change. The consequence of the polymorphism site has not been known. In Caucasian, there is a reported T398N polymorphism. In these Chinese subjects, we did not find polymorphism at this site.

China↗
PubMed2001

[The mouse model and human disease].

The mouse is an ideal model organism for studies of human disease, because mouse is physiologically very similar to human. Also, there is a large genetic reservoir of potential models of human diseases that has been generated. In addition, high-resolution genetic and physical linkage maps are now available and the sequence of mouse genome will be completed in the near future. Furthermore, the techniques necessary for the modification of mouse genome, such as transgenic and knockout techniques, and chromosome engineering methods have been established. These techniques enable us to introduce any mutations anywhere in the mouse genome. The methods for analyzing complex genetic diseases also have been developed. These advances facilitate the identification and cloning of mouse disease loci and the establishment of new models. It makes mouse the model organism of choice by academic and industrial researchers to study human diseases. In Part I of this review, we summarize the classical and modern approaches that provide the basis of establishing mouse model of human diseases. In the following parts, we will list more than 100 mouse models of human diseases. In most of these models, the mouse mutant phenotype closely resembles the human disease phenotype. These mouse models are valuable sources for the understanding of the human diseases and they can be used to develop strategies for prevention and treatment of the diseases.

Animals↗
PubMed2000

The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a.

Exon shuffling is thought to be an important mechanism for evolution of new genes. Here we show that the mouse neurological mutation flailer (flr) expresses a novel gene that combines the promoter and first two exons of guanine nucleotide binding protein beta 5 (Gnb5) with the C-terminal exons of the closely linked Myosin 5A (MyoVA) gene (Myo5a). The flailer protein, which is expressed predominantly in brain, contains the N-terminal 83 amino acids of Gnb5 fused in-frame with the C-terminal 711 amino acids of MyoVA, including the globular tail domain that binds organelles for intracellular transport. Biochemical and genetic studies indicate that the flailer protein competes with wild-type MyoVA in vivo, preventing the localization of smooth endoplasmic reticulum vesicles in the dendritic spines of cerebellar Purkinje cells. The flailer protein thus has a dominant-negative mechanism of action with a recessive mode of inheritance due to the dependence of competitive binding on the ratio between mutant and wild-type proteins. The chromosomal arrangement of Myo5a upstream of Gnb5 is consistent with non-homologous recombination as the mutational mechanism. To our knowledge, flailer is the first example of a mammalian mutation caused by germ line exon shuffling between unrelated genes.

Amino Acid Sequence↗
PubMed2000

Effects of sodium deoxycholate and sodium caprate on the transport of epirubicin in human intestinal epithelial Caco-2 cell layers and everted gut sacs of rats.

The effects of sodium deoxycholate (Deo-Na), a bile salt, and sodium caprate (Cap-Na), a fatty acid, on the transport of epirubicin were investigated in both the human colon adenocarcinoma (Caco-2) cell line and the everted gut sacs of the rat jejunum and ileum. The possible use of these two potent absorption enhancers as multidrug resistance (MDR) reversing agents also was examined. Epirubicin uptake experiments using a flow cytometer showed that Deo-Na and Cap-Na significantly increased the accumulation of epirubicin in Caco-2 cells. These two enhancers significantly increased apical to basolateral absorption of epirubicin across Caco-2 monolayers and mucosal to serosal absorption of epirubicin in the rat jejunum and ileum. Moreover, the addition of Deo-Na or Cap-Na significantly reduced the basolateral to apical efflux of epirubicin across Caco-2 monolayers. The co-presence of verapamil, one typical P-glycoprotein (P-gp) substrate, and Deo-Na or Cap-Na demonstrated further reduction of epirubicin efflux. The study suggests that inhibition of P-gp or other transporter proteins located in the intestines may be involved, at least partially, in the reduction of epirubicin efflux. In conclusion, the therapeutic efficacy of epirubicin may be improved by the use of such low toxicity excipients as absorption enhancers and MDR modulators in formulations.

Animals↗
PubMed2000

[The determination of activated partial thromboplastin time, coagulate time and thrombin time in patients with epistaxis of indeterminate cause].

OBJECTIVE: To explore the coagulation mechanism of indeterminate epistaxis. METHOD: 36 cases with epistaxis of indeterminate cause were studies by mean of detecting activated partial thromboplastin time (APTT), coagulate time (CT) and thrombin time. The results of first APTT, APTT after 8 min and CT were observed. RESULT: 1. The first APTT in epistaxis and normal group didn't show statistical difference (P > 0.05). But the APTT after 8 min in epistaxis were significantly different compared with the first APTT and that in normal group (P < 0.01). 2. The CT prolonged in 33.3% patients with epistaxis, which was higher significantly than that in the normal group (P < 0.01). (3) The epistaxis thrombin time (TT) was longer than that in normal group. CONCLUSION: The result suggest that during blood coagulation in indeterminate epistaxis, the activated factors in internal coagulating system may decompose more quickly than that in normal group. Antiagglutinating factors increase in blood.

Adolescent↗
PubMed1999

Direct interaction of microtubule- and actin-based transport motors.

The microtubule network is thought to be used for long-range transport of cellular components in animal cells whereas the actin network is proposed to be used for short-range transport, although the mechanism(s) by which this transport is coordinated is poorly understood. For example, in sea urchins long-range Ca2+-regulated transport of exocytotic vesicles requires a microtubule-based motor, whereas an actin-based motor is used for short-range transport. In neurons, microtubule-based kinesin motor proteins are used for long-range vesicular transport but microtubules do not extend into the neuronal termini, where actin filaments form the cytoskeletal framework, and kinesins are rapidly degraded upon their arrival in neuronal termini, indicating that vesicles may have to be transferred from microtubules to actin tracks to reach their final destination. Here we show that an actin-based vesicle-transport motor, MyoVA, can interact directly with a microtubule-based transport motor, KhcU. As would be expected if these complexes were functional, they also contain kinesin light chains and the localization of MyoVA and KhcU overlaps in the cell. These results indicate that cellular transport is, in part, coordinated through the direct interaction of different motor molecules.

Actins↗
PubMed1999

G169R mutation diminishes the metabolic activity of CYP2D6 in Chinese.

The molecular basis of the reduced ability of a Chinese to metabolize debrisoquine was explored by sequencing all of the nine exons of the CYP2D6 gene. The subject has T188, A1846, T2938, and C4268 (CYP2D6*14) instead of C188, G1846, C2938, and G4268 as in wild-type subjects. XbaI restriction fragment length polymorphism indicated that the subject has a 29-kb allele and a gene deletion (11.5 kb) in another allele (CYP2D6*5). A CYP2D6*14 allele together with a CYP2D6*5 allele may cause the poor metabolism of the subject. T188, T2938, and C4268 are common haplotypes in Chinese-extensive metabolizers. The effect of G1846 to A mutation in CYP2D6 metabolism has not been reported. A polymerase chain reaction-based endonuclease digestion test was designed for the G/N1846 polymorphism and 124 Chinese subjects were screened. With DNA sequencing, two other subjects showed the heterozygous G/A1846 and have a relatively high metabolic ratio of debrisoquine hydroxylation. The site-directed mutagenesis was used to create recombinant CYP2D6 cDNA with T188, A1846, or C4268. The cDNA was then transfected into Rat-1 cells. The transfection was confirmed by Southern, Northern, and Western blots. Based on the same microsomal protein level, the bufuralol 1'-hydroxylation activity of CYP2D6(T188) or CYP2D6(A1846) was significantly lower than that of the wild-type CYP2D6. P34S mutation (C188 to T) significantly decreased CYP2D6 activity. G169R mutation (G1846 to A) also decreased CYP2D6 activity and may further reduce the metabolic activity of CYP2D6 protein with P34S, R296C, and S486T mutations.

Alleles↗
PubMed1999

Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in Chinese.

Despite a wide interindividual variation of cytochrome P-450 1A2 (CYP1A2) activity, genetic polymorphism of CYP1A2 has not been reported. By amplification of exons of CYP1A2 by polymerase chain reaction in eight Chinese subjects, the polymerase chain reaction products were directly sequenced. One subject showed heterozygous C2866-->G (Phe21-->Leu) polymorphism. DNA from 157 Chinese subjects (104 polychlorinated biphenyl-exposed subjects and 53 control subjects) was screened for polymorphism by single-strand conformation polymorphism method and MboII endonuclease digestion. Only 1 of 157 samples showed another heterozygous C2866-->G mutation. The subject was previously exposed to polychlorinated biphenyl and showed a value of 3.5% in the caffeine breath test. The value is not significantly higher than the mean value of polychlorinated biphenyl-exposed subjects (3.12 +/- 0.29%, mean +/- S.E.M.). The incidence of the point mutation in these Chinese subjects is less than 1%. The prevalence of the F21L mutation in other ethnic groups and its effect on the metabolic activity of CYP1A2 remain to be further evaluated.

Asian People↗
PubMed1998

Molecular genetic dissection of mouse unconventional myosin-VA: head region mutations.

The mouse dilute (d) locus encodes unconventional myosin-VA (MyoVA). Mice carrying null alleles of dilute have a lightened coat color and die from a neurological disorder resembling ataxia and opisthotonus within three weeks of birth. Immunological and ultrastructural studies suggest that MyoVA is involved in the transport of melanosomes in melanocytes and smooth endoplasmic reticulum in cerebellar Purkinje cells. In studies described here, we have used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles that vary in their effects on coat color and the nervous system. Seven of these mutations mapped to the MyoVA motor domain and are reported here. Crystallographic modeling and mutant expression studies were used to predict how these mutations might affect motor domain function and to attempt to correlate these effects with the mutant phenotype.

Alleles↗
PubMed1998

Molecular genetic dissection of mouse unconventional myosin-VA: tail region mutations.

We used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles, a mouse-coat-color locus encoding unconventional myosin-VA. Ten of the mutations mapped to the MyoVA tail and are reported here. These mutations represent the first extensive collection of tail mutations reported for any unconventional mammalian myosin. They identify sequences important for tail function and identify domains potentially involved in cargo binding and/or proper folding of the MyoVA tail. Our results also provide support for the notion that different myosin tail isoforms produced by alternative splicing encode important cell-type-specific functions.

Animals↗
PubMed1997

The endocrine mechanism of sex reversal in the protandrous black porgy, Acanthopagrus schlegeli: a review.

Black porgy, Acanthopagrus schlegeli Bleeker, a marine protandrous hermaphrodite, is a functional male for the first 2 years of life but begin to sexually reverse to female after the third year. This sex pattern provides a very good model to study the mechanism of sex reversal in fish. The gonad at 5 month of age consisted of testicular tissue with few primary oocytes at 5 month of age. The ovarian tissue became dominant at 18 months of age during the non-spawning season. Testicular and ovarian tissues were separated by connective tissue. Plasma estradiol-17 beta(E2), vitellogenin and 11-ketotestosterone (11-KT) profiles in males were significantly different from those in the 3-year-old reversing females. Peak levels of plasma E2 in the reversing females occurred during the early prespawning season (in October). Lower levels of plasma E2 were, however, observed in the males. Plasma 11-KT levels significant decreased but no changes of plasma testosterone were detected in the reversing females. Exogenous E2 suppressed the testicular development but induced the gonadal aromatase activity, ovarian development and sex reversal in 2-year-old black porgy. Exogenous T and LHRH analog did not have effects on the sex reversal. Higher concentrations of pituitary GtH II and mRNA of GtH II-beta subunit were detected in the reversed females. These data suggested that E2 and gonadal aromatase closely associated to the occurrence of sex reversal. A working model of the sex reversal in black porgy is proposed.

Animals↗