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Biomedical subjects

K C Liu

Publications and source records attributed to K C Liu.

At least 19 recordsLinked to original sources
PubMed2001

Characterization of the murine Lbx2 promoter, identification of the human homologue, and evaluation as a candidate for Alström syndrome.

The murine Lbx2 gene is a member of the ladybird family of homeobox genes, which is expressed in the developing urogenital system, eye, and brain. Using transgenic mice, we demonstrate that 9 kb of the 5' flanking region of mouse Lbx2 is able to direct expression of a reporter gene in a tissue-specific manner recapitulating the endogenous expression pattern. This regulatory region provides a novel reagent allowing for transgenic expression in the developing urogenital ridge. In addition, we describe the identification of the human homologue, LBX2. Comparison of the human LBX2 and mouse Lbx2 sequences upstream of the coding regions reveals sequence conservation suggesting conserved regulatory regions. Both the human LBX2 and the mouse Lbx2 genes have similar genomic structures and are composed of two exons separated by an intron. We mapped the mouse Lbx2 gene to 35 cM on chromosome 6 and the human LBX2 gene to a homologous region of chromosome 2p13. This is a candidate region for several inherited disorders, including Alström syndrome, a disorder that includes ocular, urogenital, and renal abnormalities. Given the expression pattern of Lbx2, the chromosomal location in humans, and the potential function of mammalian ladybird genes, we have begun to analyze patients with ocular disorders and those with Alström syndrome for mutations in LBX2. Although polymorphisms were identified, our results indicate that mutations in the coding region of LBX2 do not account for Alström syndrome in the six kindreds analyzed.

Amino Acid Sequence↗
PubMed2001

Cyclopeptide alkaloids from stems of Paliurus ramossisimus.

Three 13-membered cyclopeptide alkaloids, paliurines G, H and I, together with six known alkaloids, nummularine H, daechuine-S3, paliurines A-C and F, were isolated from the stem of Paliurus ramossisimus by a combination of centrifugal partition chromatography and preparative TLC. Their structures were characterized and established on the basis of spectral analysis. A preliminary study indicated that nummularine H could shorten the methohexital induced sleeping time.

Alkaloids↗
PubMed2000

Cyclopeptide alkaloids from Paliurus ramossisimus.

Seven zizyphine A-type cyclopeptide alkaloids were isolated from the roots of Paliurus ramossisimus by the combination of centrifugal partition chromatography and conventional separation methods. The novel structures of paliurines A-F (1-6) were characterized and established on the basis of MS and elaborate NMR spectral analyses. Terminal dipeptide stereochemistry was confirmed by correlation with the synthetic dipeptides via comparison of their (13)C NMR data.

Alkaloids↗
PubMed1999

Lbx2, a novel murine homeobox gene related to the Drosophila ladybird genes is expressed in the developing urogenital system, eye and brain.

We describe the cloning, expression pattern, and genomic organization of Lbx2, a murine homologue of the Drosophila and mammalian ladybird genes. Lbx2 includes a homeodomain motif most closely related to those of Lbx1 and the Drosophila ladybird proteins. Lbx2 transcripts are first detected at E10.5 when they are located in the gonadal component of the urogenital ridge. Expression of Lbx2 dramatically increases by E11.5 in the urogenital ridges, and in the cranial surface ectoderm. At later stages, Lbx2 transcripts are expressed in the brain and organs derived from the urogenital ridge, including the gonadal tubercle, kidneys, and adrenal glands. From E14.5 to birth, Lbx2 expression is evident in the developing retinal neuroepithelium and the vibrissa.

Amino Acid Sequence↗
PubMed1999

Antiviral tannins from two Phyllanthus species.

Seven ellagitannins isolated from Phyllanthus myrtifolius and P. urinaria (Euphorbiaceae) have been shown, for the first time, to be active against Epstein-Barr virus DNA polymerase (EBV-DP) at the microM level. All these compounds have the same moiety of a corilagin, and differ from each other by different substitutions at C-2 and C-4 of the glucose core. SAR analysis and molecular modeling reveal that the essential pharmacophore of these tannins resides in the corilagin moiety. The outer complex carboxylic acid moieties appear to act only as auxopharmacore.

Antiviral Agents↗
PubMed1999

Transgenic rescue of congenital heart disease and spina bifida in Splotch mice.

Pax3-deficient Splotch mice display neural tube defects and an array of neural crest related abnormalities including defects in the cardiac outflow tract, dorsal root ganglia and pigmentation. Pax3 is expressed in neural crest cells that emerge from the dorsal neural tube. Pax3 is also expressed in the somites, through which neural crest cells migrate, where it is required for hypaxial muscle development. Homozygous mutant Splotch embryos die by embryonic day 14. We have utilized the proximal 1.6 kb Pax3 promoter and upstream regulatory elements to engineer transgenic mice reproducing endogenous Pax3 expression in neural tube and neural crest, but not the somite. Over expression of Pax3 in these tissues reveals no discernible phenotype. Breeding of transgenic mice onto a Splotch background demonstrates that neural tube and neural crest expression of Pax3 is sufficient to rescue neural tube closure, cardiac development and other neural crest related defects. Transgenic Splotch mice survive until birth at which time they succumb to respiratory failure secondary to absence of a muscular diaphragm. Limb muscles are also absent. These results indicate that regulatory elements sufficient for functional expression of Pax3 required for cardiac development and neural tube closure are contained within the region 1.6 kb upstream of the Pax3 transcriptional start site. In addition, the single Pax3 isoform used for this transgene is sufficient to execute these developmental processes. Although the extracellular matrix and the environment of the somites through which neural crest migrates is known to influence neural crest behavior, our results indicate that Pax3-deficient somites are capable of supporting proper neural crest migration and function suggesting a cell autonomous role for Pax3 in neural crest.

Animals↗
PubMed1998

APC in the regulation of intestinal crypt fission.

The functional effects of APC (adenomatous polyposis coli gene) germ-line mutations on crypt fission and cell proliferation were investigated in the normal intestine of human familial adenomatous polyposis (FAP) and multiple intestinal neoplasia (MIN) mice. Compared with controls, there was a 19-fold increase in the proportion of crypts in fission in FAP colon [95 per cent confidence interval (CI): 11-32, P < 0.0001], and a 75 and 61 per cent increase in MIN colon (95 per cent CI: 1.08-2.82, P < 0.02) and small bowel, respectively (95 per cent CI: 1.31-1.99, P < 0.001). In marked contrast, no significant differences in intra-cryptal epithelial cell proliferation or mitotic distribution were seen. Furthermore, 10.9 per cent of crypts in FAP were in asymmetrical fission as opposed to only 1 per cent in controls (P = 0.001). The largest relative increases in MIN crypt fission were in the colon (proximal and distal colon:190 per cent, P = 0.02 and 83 per cent, P = 0.01), suggesting that Apc mutations exert their maximal influence site-specifically. However, sites with the highest relative increases were also those with the largest eventual tumour sizes, but not the highest polyp counts. Three-dimensional serial section reconstruction analysis corroborated that FAP adenomas enlarge by crypt fission, which was frequently both asymmetrical and atypical. It is proposed that the absence of an increase in intestinal cell division infers that APC regulates intestinal crypt differentiation, specifically through the crypt cycle. This role appears analogous to the control of axis re-duplication in embryonic development, when downstream targets of APC are over-expressed. It is concluded that in vivo, the major defect in pre-neoplastic intestine harbouring APC mutations is elevated rates of crypt fission, and that this is also the mode by which micro-adenomas enlarge.

Adenoma↗
PubMed1998

Brittle-1, an adenylate translocator, facilitates transfer of extraplastidial synthesized ADP--glucose into amyloplasts of maize endosperms.

Amyloplasts of starchy tissues such as those of maize (Zea mays L.) function in the synthesis and accumulation of starch during kernel development. ADP-glucose pyrophosphorylase (AGPase) is known to be located in chloroplasts, and for many years it was generally accepted that AGPase was also localized in amyloplasts of starchy tissues. Recent aqueous fractionation of young maize endosperm led to the conclusion that 95% of the cellular AGPase was extraplastidial, but immunolocalization studies at the electron- and light-microscopic levels supported the conclusion that maize endosperm AGPase was localized in the amyloplasts. We report the results of two nonaqueous procedures that provide evidence that in maize endosperms in the linear phase of starch accumulation, 90% or more of the cellular AGPase is extraplastidial. We also provide evidence that the brittle-1 protein (BT1), an adenylate translocator with a KTGGL motif common to the ADP-glucose-binding site of starch synthases and bacterial glycogen synthases, functions in the transfer of ADP-glucose into the amyloplast stroma. The importance of the BT1 translocator in starch accumulation in maize endosperms is demonstrated by the severely reduced starch content in bt1 mutant kernels.

Adenosine Diphosphate Glucose↗
PubMed1997

Antiplatelet effects of some aporphine and phenanthrene alkaloids in rabbits and man.

Two aporphines (boldine and laurolitsine) and five phenanthrene alkaloids (litebamine, secoboldine, N-cyanosecoboldine, N-methylsecoglaucine and N-methylsecopredicentrine) were evaluated in-vitro for their ability to inhibit platelet aggregation. All seven alkaloids inhibited aggregation of rabbit platelets and inhibited the release of ATP induced by arachidonic acid and collagen in rabbit platelets. Those aggregations induced by platelet-activating factor (PAF), thrombin, U46619 and ADP were inhibited by the three N-substituted secoboldine derivatives only. Thromboxane B2 formation caused by arachidonic acid was also suppressed by these compounds. They did not affect the generation of [3H]inositol monophosphate caused by collagen, PAF and thrombin in the presence of indomethacin. Platelet cyclic AMP level was unaffected by litebamine, but was increased by N-methylsecoglaucine. Litebamine suppressed the secondary aggregation, but not the primary aggregation, induced by ADP and adrenaline in platelet-rich plasma from man, whereas N-methylsecoglaucine inhibited both primary and secondary aggregation. It is concluded that the antiplatelet effect of these seven aporphine and phenanthrene alkaloids is mainly a result of inhibition of thromboxane A2 formation; N-methylsecoglaucine has additional antiplatelet activity as a result of increasing the levels of platelet cyclic AMP.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Six lignans from Phyllanthus myrtifolius.

Six lignans comprising phyllamyricins D (1), E (2), and F (3) and phyllamyricosides A (4), B (5), and C (6) were isolated in a continuing study of Phyllanthus myrtifolius. Compounds 1 and 2 are 2a-methoxy-4-aryl-2,3-naphthalides. Compounds 3-6 belong to the 4-arylnaphthalene class, with compounds 4-6 being O-beta-glucosides. Their structures were elucidated on the basis of spectral analysis. Compound 4 increased the activity of HIV-1 reverse transcriptase by 65% at a concentration of 1.89 microM.

HIV Reverse Transcriptase↗
PubMed1995

Differential inhibition of reverse transcriptase and cellular DNA polymerase-alpha activities by lignans isolated from Chinese herbs, Phyllanthus myrtifolius Moon, and tannins from Lonicera japonica Thunb and Castanopsis hystrix.

Two lignans, phyllamycin B and retrojusticidin B isolated from Phyllanthus myrtifolius Moon have been demonstrated to have a strong inhibitory effect on human immunodeficiency virus-1 reverse transcriptase activity (HIV-1 RT), but much less inhibitory effect on human DNA polymerase-alpha (HDNAP-alpha) activity. Fifty percent inhibitory concentrations of phyllamycin B and retrojusticidin B were determined to be 3.5 and 5.5 microM for HIV-1 RT, and 289 and 989 microM for HDNAP-alpha, respectively. The mode of inhibition was found to be non-competitive inhibition with respect to template-primer and triphosphate substrate. Several tannins such as caffeoylquinates (CQs) isolated from Lonicera japonica Thunb, galloylquinates (GQs) and galloylshikimates (GSs) purified from Castanopsis hystrix were shown to have a much less selective inhibitory effect on HIV-1 RT.

DNA Polymerase II↗
PubMed1995

Mechanical and electrophysiological effects of a hydroxyphenyl-substituted tetrahydroisoquinoline, SL-1, on isolated rat cardiac tissues.

The mechanisms of the positive inotropic action of a new synthetic tetrahydroisoquinoline compound, SL-1, were investigated in isolated rat cardiac tissues and ventricular myocytes. SL-1 produced a rapidly developing, concentration-dependent positive inotropic response in both atrial and ventricular muscles and a negative chronotropic effect in spontaneously beating right atria. The positive inotropic effect was not prevented by pretreatment with reserpine (3 mg/kg) or the alpha-adrenoceptor antagonist prazosin (1 microM), but was suppressed by either the beta-adrenoceptor antagonist atenolol (3 microM) or the K+ channel blocker 4-aminopyridine (4AP, 1mM). In the whole-cell recording study, SL-1 increased the plateau level and prolonged the action potential duration in a concentration-dependent manner and decreased the maximum upstroke velocity (Vmax) and amplitude of the action potential in isolated rat ventricular myocytes stimulated at 1.0 Hz. On the other hand, SL-1 had little effect on the resting membrane potential, although it caused a slight decrease at higher concentrations. Voltage clamp experiments revealed that the increase of action potential plateau and prolongation of action potential duration were associated with an increase of Ca2+ inward current (ICa) via the activation of beta-adrenoceptors and a prominent inhibition of 4AP-sensitive transient outward K+ current (Ito) with an IC50 of 3.9 microM. Currents through the inward rectifier K+ channel (IK1) were also reduced. The inhibition of Ito is characterized by a reduction in peak amplitude and a marked acceleration of current decay but without changes on the voltage dependence of steady-state inactivation. In addition to the inhibition of K+ currents, SL-1 also inhibited the Na+ inward current (INa) with an IC50 of 5.4 microM, which was correlated with the decrease of Vmax. We conclude that the positive inotropic effect of SL-1 may be due to an increase in Ca2+ current mediated via partial activation of beta-adrenoceptors and an inhibition of K+ outward currents and the subsequent prolongation of action potentials.

Action Potentials↗
PubMed1995

The Hong Kong vascularized temporalis fascia flaps for optimal, mastoid cavity reconstruction.

The classical modified radical mastoidectomy offers the advantages of combining the mastoid cavity, the attic and the external canal into one cavity that remains open for inspection. However the ultimate goal to predictably produce well healed, dry and safe mastoid cavities despite receiving much attention has not been fulfilled. By employing basic surgical principles of wide access to facilitate meticulous removal of all cholesteatoma and then eliminating all raw surfaces of the bony cavity with pedicled vascularized deep temporalis fascia, the Hong Kong Flap technique achieves the highest percentage of dry, stable, disease free ears. This living fibrous tissue layer provides the optimal substrate for epithelial resurfacing while separating the mucosa and bone of the middle ear and mastoid from the surface epithelium. Excellent healing even under unfavourable circumstances is ensured by the rich blood supply to the pedicled temporalis fascia flap. Furthermore the technique obviates the need for second look procedures in more than two-thirds of cases as the cavity lining becomes transparent and simple observation is safe. The Hong Kong Flap was used to reconstruct 107 cavities between October 1988 and October 1992. 86 were performed for primary cholesteatoma removal and 21 for revision of discharging cavities. 103 (96%) healed soundly. There were 4 dry perforations. Minor complications occurred in 8 (7%) patients. 84 (78%) required n+o second exploratory operation. This is a straight forward procedure requiring no special technical skills. The concept is rational and provides the ideal management for cholesteatoma by achieving a dry, safe ear with one operation.

Cholesteatoma, Middle Ear↗
PubMed1992

The migration pathway of epithelial cells on human duodenal villi: the origin and fate of 'gastric metaplastic' cells in duodenal mucosa.

The specific migration pathways which epithelial cells take as they migrate through the human villus is unknown, although there have been several speculations. The well-known phenomenon of 'gastric metaplasia' in the human duodenum is readily demonstrable by the diastase periodic acid Schiff (dPAS) method. However, there is no general agreement on whether the origin of this cell lineage is the villus epithelial cells or proliferative crypt cells. Using serial sections, model building and computer-aided three-dimensional reconstruction we have followed the pathway of migration of these metaplastic cells in human duodenal villi and report: (1) that these cells migrate in straight lines; (2) that migration is in relatively tight cohorts or migration streams; (3) that a single vestibule can supply cells to more than one villus; and (4) that the cell lineage has a complex origin, deriving either from Brunner's gland duct epithelium or from basal buds growing out of the crypts of Lieberkühn.

Cell Movement↗
PubMed1990

Stomal recurrence: a separate entity?

Uncertainty exists concerning the exact aetiology of stomal recurrence following laryngectomy, although it is generally agreed that, when present, the prognosis is very poor. Fourteen cases of stomal recurrence were compared with 15 cases of other types of aggressive recurrence in the neck, for factors implicated in stomal recurrence. Similarities exist between the two groups and, although stomal recurrence has a greater association with subglottic tumour, this difference is not statistically significant. The possible mechanisms of recurrence are discussed, particularly in relation to aggressiveness, and it is concluded that factors involved in aggressive recurrences are similar. Stomal recurrence can be considered part of a group of aggressive neck recurrences associated with more advanced disease prior to laryngectomy.

Carcinoma, Squamous Cell↗