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Biomedical subjects

T T Liu

Publications and source records attributed to T T Liu.

At least 37 records · Page 2Linked to original sources

Asymmetric growth and development of the Xenopus laevis retina during metamorphosis is controlled by type III deiodinase.

During the metamorphosis of the Xenopus laevis retina, thyroid hormone (TH) preferentially induces ventral ciliary marginal zone (CMZ) cells to both increase their proliferation and give rise to ipsilaterally projecting ganglion cells. Here we show that dorsal CMZ cells express type III deiodinase (D3), an enzyme that inactivates TH. The dorsal CMZ cells can be induced to proliferate if deiodinase activity is inhibited. D3 or dominant-negative thyroid hormone receptor transgenes inhibit both TH-induced proliferation of the ventral CMZ cells and the formation of the ipsilateral projection. Thus, the localized expression of D3 in the dorsal CMZ cells accounts for the asymmetric growth of the frog retina.

Animals↗

Reversal of spontaneous progressive autoimmune encephalomyelitis by myelin basic protein-induced clonal deletion.

Autoimmune encephalomyelitis can be initiated spontaneously and developed progressively in TCR transgenic mice specific for myelin basic protein when exposed to non-sterile environment, thus more closely mimicking human multiple sclerosis. By intravenous administration of myelin basic protein, we succeeded in reversing the clinical and pathological signs of progressive spontaneous disease in these mice. Flow cytometry showed that the majority of transgenic T cells in lymph nodes and spleen as well as spinal cords of treated mice were deleted. Dramatically increased numbers of apoptotic cells were found in peripheral immune organs of treated animals. Proliferative responses of single transgenic T cell to autoantigen were significantly decreased in treated mice, indicating that the remaining T cells were anergic. Moreover, production of both Th1 and Th2 cytokines was suppressed. This study is the first demonstration of reversal of progressive, spontaneous autoimmune disease of the central nervous system, and provides direct evidence that apoptosis-induced clonal deletion, along with anergy of remaining cells, but not Th2 switch, play a major part in the reversal of this disease by intravenous administration of autoantigen.

Animals↗

Mutation analysis of the 6-pyruvoyl-tetrahydropterin synthase gene in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency.

Hyperphenylalaninemia (HPA) may be caused by deficiency of phenylalanine hydroxylase or tetrahydrobiopterin (BH4), the essential cofactor for the aromatic amino acid hydroxylases. 6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is a major cause of BH4 deficient HPA. In this study, seven single base mutations at nucleotides 73 (C>G), 155 (A>G), 166 (G>A), 209 (T>A), 259 (C>T), 286 (G>A), and 317 (C>T) on PTPS cDNA were detected in Chinese PTPS-deficient HPA by polymerase chain reaction and solid phase DNA sequencing. These nucleotide alterations result in R25G, N52S, V56M, V70D, P87S, D96N, and T106M amino acid substitutions, respectively. The R25G, V56M, V70D, and T106M were novel mutations found in PTPS gene. By analysis of 38 PTPS mutant alleles from 19 unrelated Chinese PTPS-deficient HPA families, the allele frequency of these mutations in Chinese PTPS-deficient HPA were determined to be approximately 5.3% (R25G), 34.2% (N52S), 7.9% (V56M), 2.6% (V70D), 36.8% (P87S), 7.9% (D96N), and 2.6% (T106M), respectively. Two common mutations, N52S and P87S, were found to account for 71% of the Chinese PTPS mutant alleles. The N52S mutation accounts for 48% of the southern Chinese PTPS mutation, but only one (9%) of the northern Chinese PTPS mutant allele was found to be N52S, which suggested that the N52S mutation might be southern Chinese. Clinically, the V56M mutation was found to associate with the mild form of PTPS deficiency. However, the R25G, N52S, P87S, and D96N were found mainly in the patients with severe clinical symptom. Using polymerase chain reaction-based mutation analysis, a fetus at risk of PTPS deficiency was diagnosed prenatally to be a carrier of N52S mutation.

Alcohol Oxidoreductases↗

Expression of the tobacco anionic peroxidase gene is tissue-specific and developmentally regulated.

Transcriptionally regulated expression of tobacco anionic peroxidase was investigated with regard to tissue specificity and developmental regulation. Two tobacco species, Nicotiana sylvestris and Nicotiana tabacum cv. Xanthi, were stably transformed with a gene chimera composed of 3 kb of the tobacco anionic peroxidase promoter, the Escherichia coli beta-glucuronidase (GUS) coding region and the nopaline synthase terminator. Gene expression was regulated spatially and developmentally in all organs, and generally increased with age and maturity of the plant, tissue or organ. In the aerial portions of the plant, GUS activity was strongly expressed in trichomes and epidermis at nearly all developmental stages. In later stages of development, activity was also detected in ground tissue and parenchyma cells associated with vascular tissues. Activity in roots was limited to cortical cells and vascular-associated parenchyma cells. In reproductive tissue, expression was observed in sepals and petals before anthesis, and in all floral organs after anthesis. Expression was never detected in vascular tissue and was poorly correlated with lignification except in the cells surrounding primary xylem and pericyclic fibers in N. sylvestris. These studies suggest that this peroxidase isoenzyme is only limitedly involved in lignification but may be important in plant defense, growth and development.

Cell Wall↗

Isolation and characterization of the mitochondrial channel, VDAC, from the insect Heliothis virescens.

A 31 kDa voltage-dependent anion-selective channel (VDAC) protein was purified from the insect Heliothis virescens (tobacco budworm, denoted TBW) using an alkali extraction and filtration procedure and was characterized by SDS-PAGE, amino acid sequencing, biophysical properties and immunocytochemistry. The N-terminal sequence has highest identity with VDACs from mammals (50-66%) followed by plants (34-41%) and lower eukaryotes (30-34%). Reconstitution in planar phospholipid membranes yielded properties typical of VDACs from other organisms including a single-channel conductance of 4.1 nS (in 1 M KCl), closure in response to positive and negative transmembrane voltage, and a reversal potential of 11.8 mV indicating anion selectivity in the open state. A polyclonal antiserum (R19) raised against gel-purified 31 kDa protein specifically labelled mitochondria and mitochondrial outer membranes in TBW flight muscle by light and electron microscope immunocytochemistry.

Amino Acid Sequence↗

Breast mass due to alveolar soft part sarcoma of the pectoris major muscle.

We present a case of alveolar soft part sarcoma (ASPS) of the pectoris major muscle in a 20-year-old female. She felt a mass in her right side breast for 7 years. The lesion was almost the same size with occasional throbbing pain and tenderness. Fine needle aspiration of the tumor was performed in the OPD and suspicious abnormal cells were reported. Ultrasound (US) examination of the breast revealed a large heterogeneously hypoechoic lesion contiguous to the pectoris major muscle. Profound color flow signals were evident in both central and peripheral regions of the mass. Spectral Doppler US showed high flow velocity in the tumor vessels with resistivity index of 0.73. Surgical intervention was performed and the histological examination yielded a diagnosis of ASPS.

Adolescent↗

The consequence of peroxidase overexpression in transgenic plants on root growth and development.

Transgenic tobacco plants that overproduce the tobacco anionic peroxidase wilt upon reaching maturity, although having functional stomata and normal vascular anatomy and physiology. These plants were examined further to determine the cause for wilting, and thus better understand how the anionic peroxidase functions in plant growth and development. Shoots from young peroxidase overproducing plants were grafted onto wild-type tobacco root stock to determine if the roots could absorb and transmit sufficient water to maintain leaf turgidity. These grafted plants never wilted when grown in the greenhouse though shoot peroxidase activity remained ten-fold greater than in control plants, thus indicating that wilting is a consequence of peroxidase expression in the roots. Close examination of root systems revealed considerably less root mass in the transformed plant, primarily exhibited through a decrease in branching. At flowering, root growth rate and total root mass in transformed plants were less than 50% of control plants although shoot mass and growth rate were unchanged. This is in contrast to root growth in young seedlings where transformed plants performed equivalently to controls. Root hydraulic conductivity was measured to evaluate the effect of elevated peroxidase expression on water absorption and transport; however, no significant change in hydraulic conductivity was found in transformed plants. The consequence of anionic peroxidase overexpression on indoleacetic acid (IAA) metabolism was also examined. No significant difference in IAA levels was observed; however, root elongation in plants overexpressing peroxidase was insensitive to exogenous IAA. It can be concluded that the overexpression of the tobacco anionic peroxidase in transformed plants results in diminished root mass from fewer root branches, which contributes to the wilting phenomenon seen in these plants. Further, this developmental change in transformed plants may be a consequence of the metabolism of IAA by the anionic peroxidase.

Indoleacetic Acids↗

Risk factors for Alzheimer's disease: a case-control study.

The extent of current knowledge of risk factors for Alzheimer's disease (AD) is still limited. We conducted a case-control study of 98 AD patients and 98 age- and sex-matched controls. Light smoking had a decreased risk for AD (AD: 2.0%, controls: 21.4%, odds ratio = 0.10, p = 0.003), whereas daily smoking showed a trend to increase the risk for AD (AD: 45.9%, controls: 26.5%, odds ratio = 1.73, p = 0.08). After multivariable analyses factors associated with AD included the presence of apolipoprotein epsilon4 allele, and the duration of well water consumption.

Aged↗

Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin synthesis deficiency.

Deficiency in 6-pyruvoyl-tetrahydropterin synthase (PTPS) activity is the major cause of tetrahydrobiopterin (BH4)-deficient phenylketonuria. Two single base alterations of PTPS cDNA, a C-to-T transition at nucleotide 259 and a novel A-to-G transition at nucleotide 155 (according to cDNA sequence), were identified in two Chinese PTPS-deficient siblings by the reverse transcription-polymerase chain reaction (RT-PCR). The C-to-T transition at nucleotide 259 results in an amino acid change from proline to serine at codon 87 (Pro87Ser), and the A-to-G transition at nucleotide 155 causes an amino acid change from asparagine to serine at codon 52 (Asn52Ser) of PTPS. The C259T missense mutation can be identified by analysis of the BbvI restriction fragments of the PCR-amplified PTPS cDNA product, and was found to account for 42% (11/26) of 26 Chinese PTPS mutant alleles studied. However, none of 100 normal alleles screened were found to have this change. This result indicates that the C259T transition may be a common mutation in Chinese PTPS-deficient patients.

Adult↗

Reevaluation of polychlorinated biphenyl concentrations in milk and body fat of lactating cows.

Polychlorinated biphenyls occur as mixtures of congeners, each of which may be absorbed, excreted, or metabolized differently. Quantification of polychlorinated biphenyls by packed-column GLC has been difficult. Many quantification techniques, generally based on quantification of a selected group of the congeners present, have been used by researchers. Results of these studies have not provided a consistent basis to determine the relationship between the amounts of polychlorinated biphenyls consumed and residual polychlorinated biphenyls in milk and animal tissues. In the present study, we hypothesized that if a standardized quantification procedure was applied, consistent dose:residue predictions could be made. Weighted percentage of each peak in the polychlorinated biphenyl mixture procedures was used as a standard method to quantify polychlorinated biphenyls in milk fat from published and unpublished studies where lactating cows were fed between 3.5 and 1000 mg/d (Aroclor 1254) for greater than or equal to 15 d. When steady state occurred by 60 d of dosing, the relationship between concentration in milk fat (microgram/g) and daily dose as mg and as mg/kg BW were described by the equations: [polychlorinated biphenyls, microgram/g]milk fat = .28 (daily dose, mg).82, and [polychlorinated biphenyls, microgram/g]milk fat = 50.2 (daily dose, mg/kg BW).81. Similar equations described the relationships between daily dose and concentrations in adipose tissue and blood plasma. Concentrations of polychlorinated biphenyls residues in milk fat of 79 animals that were dosed with known quantities of polychlorinated biphenyls for 15 to 107 d confirmed that the equations could be valuable in predicting exposure over a wide range of exposure durations and concentrations.

Adipose Tissue↗

Study of restriction fragment length polymorphisms at the human phenylalanine hydroxylase locus and evaluation of its potential application in prenatal diagnosis of phenylketonuria in Chinese.

Using a human phenylalanine hydroxylase cDNA probe, the restriction fragment length polymorphisms at the human phenylalanine hydroxylase locus have been determined with the restriction enzymes BglII, PvuII, EcoRI + BamHI, MspI, XmnI, HindIII and EcoRV. The frequency of the observed heterozygosity of the restriction site polymorphisms at this locus in a Chinese population is approximately 54%, which is significantly lower than that in Caucasians. No DNA rearrangement or deletion of the phenylalanine hydroxylase locus was detected among mutant phenylalanine hydroxylase genes in seven Chinese classical phenylketonuria (PKU) families. Haplotype analysis of these seven families revealed that the mutant alleles belonged to five different haplotypes, i.e. haplotype 4, 11 and three unreported haplotypes. The majority of normal and mutant phenylalanine hydroxylase genes are confined to hyplotype 4. These results indicate that approximately 42% of Chinese PKU families are informative for prenatal diagnosis of PKU when eight restriction sites linked to the phenylalanine hydroxylase locus are examined.

Alleles↗

Screening of congenital hypothyroidism, phenylketonuria, galactosemia, homocystinuria, and maple syrup urine disease in moderate to severe mentally retarded Chinese children.

Five-hundred and fifty one mentally retarded children from seven institutes in Northern Taiwan were screened by dried blood spot for the detection of treatable congenital metabolic diseases, including congenital hypothyroidism, phenylketonuria, homocystinuria, maple syrup urine disease and galactosemia. We found 2 children (0.36%) with congenital hypothyroidism, 1 case (0.18%) of classical phenylketonuria and two cases (0.36%) of trisomy 21 associated with autoimmune thyroiditis. The results of our investigation suggest that congenital hypothyroidism and phenylketonuria can be the factors causing mental retardation among children in Taiwan and mass neonatal screening of these treatable inborn metabolic diseases is strongly indicated for efficiently circumventing mental retardation in our community.

Adolescent↗

The use of restriction fragment length polymorphisms for prenatal diagnosis: the estimation of diagnosable rate of multiple genetic markers and its use in detecting beta-thalassemia in a Chinese population.

As a codominant genetic marker, restriction fragment length polymorphism (RFLP) has been widely applied to the prenatal diagnosis of some genetic diseases. To evaluate the usefulness of the genetic markers in prenatal diagnosis, a parameter, the diagnosable rate or the proportion of diagnosable matings, is estimated when two or more genetic markers are used. The assessment is based on the distribution of haplotypes. By using the data of the distribution of haplotypes of beta-A (normal) and beta-T (beta-thalassemia) chromosomes in a Chinese population and the formula given, it is easy to calculate the different diagnosable rates of all the combinations of seven given genetic markers. The results could help us to find an appropriate combination of genetic markers in prenatal diagnosis and, therefore, makes it possible to obtain a sufficiently high diagnosable value with a limited number of genetic markers.

China↗

Health and productivity of dairy cows fed polychlorinated biphenyls.

Holstein cows were studied through a complete lactation, a nonlactating period, and 42 days of a subsequent lactation for overt and subtle responses to a commercial mixture of polychlorinated biphenyls. Dosed cows (n = 4) received consecutive 60-day periods of daily dosing with 10, 100, and 1000 mg of Aroclor 1254. Control cows (n = 6) received daily sham doses. The following were recorded: daily milk production, feed intake, and health observations; weekly body weight, temperature, heart and respiratory rates and rectal palpation; semi-monthly clinical chemistry determinations; and monthly milk fat, microbiological culture of quarter foremilk samples, and composite milk somatic cell counts. Mean daily milk production (22.4 +/- 1.1 vs 24.8 +/- 1.0 kg) and net energy of a complete lactation (1.46 +/- 0.05 vs 1.45 +/- 0.03 Mcal/kg dry matter intake) were not different (p = 0.85) for control and PCB-dosed cows. Milk production during the first 42 days of the subsequent lactation was also similar for control and dosed cows. Occurrences of injuries, dysfunctions, and general infections were not related to polychlorinated biphenyl exposure. Intramammary infections were detected for both lactations with 51 and 32 infections detected in microbiological cultures, respectively, for the control and dosed groups. Environmental pathogens were most frequently isolated from cases of clinically apparent mastitis. The majority of quarter infections detected were due to Corynebacterium bovis. Only one animal (dosed, necropsy revealed left oviduct obstructed) failed to conceive with three to six services required before conception for the other control and dosed cows. Exposure to polychlorinated biphenyls resulting in maximal residues in milk fat, near 100 micrograms/g, had no apparent effect on health and productivity.

Animals↗

Changes in hepatic function tests to induced toxicity in the bovine liver.

Graded hepatic damage was induced in mature lactating dairy cows to measure the sensitivity of several hepatic diagnostic tests. In a preliminary study, cows were dosed with .05, .10 and .20 ml/kg body weight of carbon tetrachloride. Extreme changes occurred in hepatic tests by 24 h post-dosing, and all died by 35 h with massive diffuse centrilobular necrosis of hepatic cord cells. Dosing was decreased to induce non-fatal hepatic changes. Cows in Groups 1, 2, 3 and 4 were orally dosed with .002, .004, .006 or .01 ml/kg body weight of carbon tetrachloride, respectively. Serum enzymes of hepatic origin, bilirubin, plus bromosulfophthalein dye clearance were assayed before dosing and up to d 14 post-dosing. Liver biopsies were performed 24 h post-dosing for histological evaluation and cytochrome P-450 content. Hepatic concentrations of cytochrome P-450 were decreased in all the dosed cows. Serum activities of sorbitol dehydrogenase and gamma-glutamyl transferase were elevated in cows of Groups 3 and 4 and glutamic-oxaloacetic transaminase in cows of Group 4 by 24 h. Serum alkaline phosphatase, glutamic-pyruvate transaminase, lactate dehydrogenase, bilirubin, urobilinogen and bromosulfophthalein dye clearance were not significantly different. Mild to moderate diffuse centrolobular necrosis was observed in livers of cow of Groups 3 and 4, but no pathological changes were seen in Groups 1 and 2.

Animals↗

Effect of hemodialysis on contrast sensitivity in renal failure.

After a brief review of the ocular aspects of hemodialysis treatment for renal failure, we report on 10 patients who underwent this treatment. Contrast thresholds over a wide range of spatial frequencies and Snellen visual acuities were measured before and after treatment. Subtle changes in vision can be monitored by the contrast sensitivity function (CSF) technique. We conclude that there are measurable changes in contrast sensitivity after hemodialysis treatment for each of the 10 patients (20 eyes).

Adult↗