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Biomedical subjects

K Liu

Publications and source records attributed to K Liu.

At least 415 records · Page 23Linked to original sources

A novel DNA duplex. A parallel-stranded DNA helix with Hoogsteen base pairing.

We show here for the first time that a stable parallel double helix with Hoogsteen pairing can exist independently of the triple helix of which it is a component part. The experiments employ DNA oligonucleotides with mixed sequences of normal bases. These duplexes are distinct from previously reported ribopolynucleotide helices containing bulky substituents which prevent Watson-Crick pairing as well as from parallel duplexes with Donohue, or reversed Watson-Crick, pairing. Stoichiometry is established by mixing curves and gel electrophoresis. Tm depends linearly upon pH, increasing with acidity because of the need to protonate N3 of C. The Tm of the 20-mer studied here is 52 degrees C at pH 5.2 and 0.1 M NaCl. At pH above 6, the molecule rearranges to form an antiparallel duplex with imperfect Watson-Crick pairing and loops, and the Tm is then independent of pH. The CD spectrum of the parallel duplex is very similar to that of the corresponding triple helix but quite different from that of the Watson-Crick helix. The infrared spectrum in the double bond region closely resembles that of the triple helix but, as with the CD, is quite different from that of the Watson-Crick duplex. The infrared spectra of the duplex and triple helix are also nearly identical in the region form 800 to 1000 cm-1, which is sensitive to backbone conformation. The only symmetry element present is a pseudorotational axis coincident with the helix axis of the parallel duplex as well as with the axis of the corresponding triple helix.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Composition↗

The action of oxidized low density lipoprotein on calcium transients in isolated rabbit cardiomyocytes.

The effect of oxidized low density lipoprotein (oxLDL) on the Ca2+ transients of isolated rabbit cardiomyocytes was assessed. LDL was oxidized by a free radical generating system in vitro. The systolic Ca2+ concentration in transients was significantly increased after treatment with 100 micrograms of oxLDL cholesterol/ml for 16 min without having any effect on the diastolic [Ca2+]. However, a toxic effect was observed when the concentration of oxLDL was increased to 1,000 micrograms/ml. Cells treated with 100 micrograms of oxLDL/ml were more sensitive to the blocking action of nicardipine on the Ca2+ transient than were control cardiomyocytes. Furthermore, oxLDL failed to produce a stimulatory effect on the transient when the extracellular [Ca2+] was lowered. The malondialdehyde content in the oxLDL correlated well with the change in systolic [Ca2+] of treated cells. Lazaroid, a novel antioxidant, completely inhibited malondialdehyde formation in the oxLDL and prevented the increment of systolic [Ca2+] in the treated cells. The data indicate that oxLDL can induce relatively rapid alterations in cellular Ca2+ transients via a modification of Ca2+ entry through the L-type Ca2+ channel. LDL oxidation induced by free radicals may play an important role in influencing cardiac contractile function during pathological conditions such as ischemia/reperfusion challenge.

Animals↗

The effects of low density lipoprotein on calcium transients in isolated rabbit cardiomyocytes.

The purpose of this study was to examine the effects of low density lipoprotein (LDL) on Ca2+ transients of isolated rabbit cardiomyocytes. Incubation of cardiomyocytes with > or = 1 mg of LDL cholesterol/ml of perfusion medium induced a slow (> or = 30 min) but significant increase (2-fold) in the cellular Ca2+ transient. The time course for the effect was similar to that observed for the accumulation of cholesterol in the cells. Using Dil- labeled LDL as a fluorescent marker for LDL interaction with the cardiomyocytes, it was concluded that LDL interacted via a receptor-mediated event, but probably this was not the primary mechanism whereby the lipid entered the cell. LDL-treated cells were resistant to the depressant actions for ryanodine, nicardipine, and dichlorobenzamil on the cellular Ca2+ transient. Lowering the extracellular Ca2+ concentration removed the stimulatory effect of LDL on the Ca2+ transient. It is concluded that LDL can induce an increase in the magnitude of the Ca2+ transient in isolated cardiomyocytes. This is a relatively slow process. The mechanism appears to involve a stimulation of a transsarcolemmal Ca2+ transport pathway. These findings have important implications for cardiac contractile function in hypercholesterolemic and drug-treated hypercholesterolemic subjects.

Amiloride↗

The yeast gene MSH3 defines a new class of eukaryotic MutS homologues.

We have identified a gene in Saccharomyces cerevisiae, MSH3, whose predicted protein product shares extensive sequence similarity with bacterial proteins involved in DNA mismatch repair as well as with the predicted protein product of the Rep-3 gene of mouse. MSH3 was obtained by performing a polymerase chain reaction on yeast genomic DNA using degenerate oligonucleotide primers designed to anneal with the most conserved regions of a gene that would be homologous to Rep-3 and Salmonella typhimurium mutS. MSH3 seems to play some role in DNA mismatch repair, inasmuch as its inactivation results in an increase in reversion rates of two different mutations and also causes an increase in postmeiotic segregation. However, the effect of MSH3 disruption on reversion rates and postmeiotic segregation appears to be much less than that of previously characterized yeast DNA mismatch repair genes. Alignment of the MSH3 sequence with all of the known MutS homologues suggests that its primary function may be different from the role of MutS in repair of replication errors. MSH3 appears to be more closely related to the mouse Rep-3 gene and other similar eukaryotic mutS homologues than to the yeast gene MSH2 and other mutS homologues that are involved in replication repair. We suggest that the primary function of MSH3 may be more closely related to one of the other known functions of mutS, such as its role in preventing recombination between non-identical sequences.

Adenosine Triphosphatases↗

Post-irradiation bladder dysfunction: development of a rat model.

The aim of this research was to establish a small animal model for the functional and morphological study of post-irradiation bladder dysfunction. Young adult female Wistar rats were X-irradiated with single doses of 10, 15, 20 or 25 Gy. Filling cystometry was performed to assess changes in reservoir function: the volume infused to produce a rise in intravesical pressure of 5 cmH2O was calculated as an index of compliance. A biphasic reduction in this index was noted in animals receiving 15-25 Gy; the first reduction developed at about 4 weeks, and the second started at 3-4 months and persisted at 6 months. Bladder tissue was taken at this time (6 months post-irradiation) for morphological study. Histological examination demonstrated an increased mast cell density in the irradiated bladders, but was otherwise non-specific; fibrosis was discernible in only half of the 18 animals studied. Electron microscopy showed focal degeneration of smooth muscle cells, and in some areas there was selective degeneration of unmyelinated axon profiles. The biphasic reduction in the compliance index is consistent with the timing of the symptoms of the acute and late irradiation reactions reported by radiotherapy patients. Changes in axon profiles and mast cell density may be of functional significance.

Animals↗

The Dietary Intervention Study in Children (DISC): dietary assessment methods for 8- to 10-year-olds.

OBJECTIVES: The dietary assessment methods used in the Dietary Intervention Study in Children (DISC) are described and the rationale, validity, and/or general usefulness of each are discussed. DESIGN: DISC is the first multicenter, randomized, clinical trial to study the feasibility and long-term efficacy, safety, and acceptability of a fat-moderately diet in 8- to 10-year-old prepubescent children with moderately elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. Final data collection for the original study (DISC I) occurred December 1, 1993; continued intervention and follow-up (DISC II) will extend beyond 1997. SETTING: Six clinical centers across the country participate in DISC. SUBJECTS: Preadolescent boys and girls with fasting LDL-C levels between the 80th and 98th age-specific and sex-specific percentiles established by the Lipid Research Clinics were eligible for the study. The feasibility phase included 140 children who were then enveloped into the full-scale trial. Baseline dietary data for 652 randomized children in the full-scale trial and 6-month results for the feasibility cohort are reported. INTERVENTIONS: Dietary assessment involved several elements: (a) determining eligibility based on consumption of more than 30% of energy from total fat, (b) monitoring adherence to and adequacy of the intervention diet, (c) evaluating acceptability of the diet in the intervention group, and (d) determining appropriate foods for the intervention diet. Methods are described for each purpose. MAIN OUTCOME MEASURES: LDL-C differences between the two groups and differences in total and saturated fat intakes as calculated from three 24-hour recalls were the primary outcome measures. Six-month dietary differences in the feasibility group are reported. STATISTICAL METHODS: Baseline group means and 6-month differences in dietary intake are reported for the full-scale trial and feasibility study, respectively. RESULTS: Baseline mean intake from three dietary recalls for the intervention (n = 328) and control (n = 324) groups, respectively, were as follows: energy = 1,759 kcal and 1,728 kcal; total energy from fat = 33.3% and 34.0%; total energy from saturated fat = 12.5% and 12.7%; and total dietary cholesterol = 209 mg and 195 mg. After 6 months of intervention, percentage of energy from total fat and saturated fat was reduced by 5.1% (P = .004) and 2.9% (P < .001), respectively, in this feasibility subset (n = 73) of the intervention group. Essentially no change in these parameters occurred in the control group (n = 67), which demonstrates a measurable difference in reporting between groups. APPLICATIONS/CONCLUSIONS: Results illustrate the feasibility of implementing a variety of dietary assessment methods among preadolescent children without relying primarily on parental reports.

Child↗

Forecasts of active life expectancy: policy and fiscal implications.

Age-related changes in functional status can be summarized by active life expectancy (ALE) measures. ALE is useful in assessing efforts to improve function and in determining a population's service needs. ALE disaggregates total life expectancy (TLE) into components representing degree and type of impairment. We illustrate the calculation of two ALE measures and their relations to health inputs and service use. First, scores are calculated from 27 measures of function for persons 65 and over, as reported in the National Long Term Care Survey (NLTCS). The scores are then used to calculate the two ALE measures. Results are compared to ALE calculated from the 1982, 1984, and 1989 NLTCS.

Activities of Daily Living↗

Catastrophic acute and long-term care costs: risks faced by disabled elderly persons.

This article presents an empirical analysis of the extent to which acute and long-term care cause disabled elderly persons to incur catastrophic costs. We found that the proportion of those people whose out-of-pocket costs exceed 20% of income rises from 20% (when only acute care costs are measured) to 30% (when long-term care costs are included).

Age Factors↗

RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae.

To investigate the role of the yeast telomere-, silencing-, and UAS-binding protein RAP1 in telomere position effects, we have characterized two sets of mutant cells: (1) a set of rap1 alleles (termed the rap1t alleles) that produce truncated RAP1 proteins missing the carboxy-terminal 144-165 amino acids; and (2) null mutants of the RIF1 gene, encoding a protein capable of interaction with the carboxyl terminus of RAP1. The data presented here indicate that loss of the carboxyl terminus of RAP1 abolishes position effects at yeast telomeres and diminishes silencing at the HML locus. Elimination of position effects in these cells is associated with increased accessibility to the Escherichia coli dam methylase in vivo. Thus, the carboxy-terminal domain of RAP1 is required for telomere position effects. In contrast, rif1 deletion alleles increase the frequency of repressed cells. Using the rap1t alleles to generate wild-type cells differing only in telomere tract lengths, we also show that telomere position effects are highly sensitive to changes in the size (or structure) of the telomeric tract. Longer poly(G1-3T) tracts can increase the frequency of transcriptional repression at the telomere, suggesting that telomeric poly(G1-3T) tracts play an active role in the formation or stability of subtelomeric transcriptional states.

Chromatin↗

Signals in chicken beta-globin DNA influence chromatin assembly in vitro.

We have confirmed the result that chicken beta-globin gene chromatin, which possesses the characteristics of active chromatin in erythroid cells, has shortened internucleosome spacings compared with bulk chromatin or that of the ovalbumin gene, which is inactive. To understand how the short (approximately 180-bp) nucleosome repeat arises specifically on beta-globin DNA, we have studied chromatin assembly of cloned chicken beta-globin DNA in a defined in vitro system. With chicken erythrocyte core histones and linker histone H5 as the only cellular components, a cloned 6.2-kb chicken beta-globin DNA fragment assembled into chromatin possessing a regular 180 +/- 5-bp repeat, very similar to what is observed in erythroid cells. A 2-kb DNA subfragment containing the beta A gene and promoter region, but lacking the downstream intergenic region between the beta A and epsilon genes, failed to generate a regular nucleosome array in vitro, suggesting that the intergenic region facilitates linker histone-induced nucleosome alignment. When the beta A gene was placed on a plasmid that contained a known chromatin-organizing signal, nucleosome alignment with a 180-bp periodicity was restored, whereas nucleosomes on flanking plasmid sequences possessed a 210-bp spacing periodicity. Our results suggest that the shortened 180-bp nucleosome spacing periodicity observed in erythroid cells is encoded in the beta-globin DNA sequence and that nucleosome alignment by linker histones is facilitated by sequences in the beta A-epsilon intergenic region.

Animals↗

Predicting the outcome of radical radiotherapy for invasive bladder cancer.

The correlation between T stage, histological grade, the presence of squamous metaplasia, and nuclear morphometry scores and response to radiotherapy and survival was investigated in 60 patients with muscle invasive transitional cell carcinomas of the bladder. Patients with T2 tumours showed a complete response significantly more often than those with T3 lesions. Multivariate analysis showed that T stage and initial response to radiotherapy were very strong predictors of survival though they were not independent variables. Histological grade, the presence of squamous metaplasia, and nuclear morphometry scores were not found to have any predictive value.

Aged↗

[The effect of iontophoresis on accelerating orthodontic tooth movement]

This paper reported that acceleration of tooth movement can be gained by submucosal injection of some kind of medicine.To avoid the pain caused by the injection,conventional drug administration was ameliorated in this study by adopting the method of ionophoresis rabibits were divided into 2 groups and the standard otthodontic appliances were placed in the lower incisors of all animals.The 2 groups were separately recieved submucosal iontophoresis and injection of 0.9% NaCl which served as control.The result showed that animals with iontophoresis,in whose periodontal pression side more osteoclasts were observed histologically,had gained rapider tooth movement than those with injections.

Journal Article↗

[The multi-channel VEPs topography in optic neuritis].

The multi-channel VEPs topographies of 20 normal persons and 22 patients suffered from optic neuritis were recorded. In normal subjects, the topography showed symmetric distribution by full-field stimulation and paradoxical lateralization by half-field stimulation. In patients with optic neuritis, it showed asymmetric distribution most on the temperal side, some on the nasal side and occasionally in the middle by full-field stimulation. The result suggests that the optic nerve may be damaged on either temperal or nasal. The effect of the early diagnosis and evaluating treatment using topography is also discussed.

Adult↗

The possible involvement of tissue type plasminogen activator in luteolysis of rhesus monkey.

Changes of plasminogen activators (PA) during different stages of development of the corpus luteum, and their possible physiological role in luteolysis were studied in rhesus monkeys. It was demonstrated for the first time that monkey corpus luteal cells not only produce PA, but that the function of the corpus luteum is also closely related to the activity of this enzyme system. Generally, the life span for a corpus luteum in monkey is approximately 14-16 days, its demise beginning thereafter. In the present study, we found that urokinase in the corpus luteum is higher on day 5 and day 10 after human chorionic gonadotrophin injection, while the tissue type (t) PA is mainly produced on day 13 when luteolysis may take place. Progesterone production remained high on day 5 and day 10 and decreased dramatically from day 13, indicating the important role of tPA but not urokinase (u) PA in suppressing luteal function. When purified tPA (but not uPA) monoclonal antibody was added to luteal cell culture to neutralize endogenously produced tPA activity, progesterone production in the cells was increased significantly. Interestingly, prolactin alone was capable of increasing PA production by luteal cells; prolactin together with luteinizing hormone, however, had a synergistic luteotrophic effect.

Animals↗