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Biomedical subjects

K Liu

Publications and source records attributed to K Liu.

At least 343 records · Page 19Linked to original sources

Impact of father's education and parental smoking status on smoking behavior in young adults. The CARDIA study. Coronary Artery Risk Development in Young Adults.

Associations of parents' education and smoking with young adults' smoking were examined in participants aged 18-30 years at baseline (1985-1986) in the Coronary Artery Risk Development in Young Adults study. Significant (p < 0.05) inverse age-adjusted associations of father's education with participant smoking status among black men, white men, and white women disappeared after adjustment for participant's education. Parental smoking status was directly related to participant smoking status for all race/sex groups. Participant education was strongly inversely related to participant smoking. Public health campaigns should consider influences of parental behaviors on children's behaviors and associations of limited education with adverse lifestyles.

Adolescent↗

NMR characterisation of a triple stranded complex formed by homo-purine and homo-pyrimidine DNA strands at 1:1 molar ratio and acidic pH.

Homo-purine (d-TGAGGAAAGAAGGT) and homo-pyrimidine (d-CTCCTTTCTTCC) oligomers have been designed such that they are complementary in parallel orientation. When mixed in a 1:1 molar ratio, the system adopts an antiparallel duplex at neutral pH with three mismatched base pairs. On lowering the pH below 5.5, a new complex is formed. The NMR results show the coexistence of a intermolecular pyrimidine.purine:pyrimidine DNA triplex and a single stranded oligopurine at this pH. The triplex is stabilized by five T.A:T, four C+.G:C and two mismatched triads, namely, C+.G-T and T.A-C. This triplex is further stabilized by a Hoogsteen C+.G base-pair on one end. Temperature dependence of the imino proton resonances reveals that the triplex dissociates directly into single strands around 55 degrees C, without duplex intermediates. Parallel duplexes are not formed under any of the conditions employed in this study.

Base Sequence↗

The structural basis for pseudoreversion of the E165D lesion by the secondary S96P mutation in triosephosphate isomerase depends on the positions of active site water molecules.

The structural basis for the improvement in catalytic efficiency of the mutant E165D chicken triosephosphate isomerase by the secondary mutation, S96P, has been analyzed using a combination of X-ray crystallography and Fourier transform infrared spectroscopy. All X-ray structures were of the complex of phosphoglycolohydroxamate (PGH), an intermediate analog, with the isomerase, and each was solved to a resolution of 1.9 A. Comparison of the structure of the double mutant, E165D.S96P, with that of the single mutant, E165D, as well as with the wild-type isomerase shows only insignificant differences in the positions of the side chains in all of the mutants when compared with the wild-type isomerase, except that in both the E165D and E165D.S96P mutants, the aspartate side chain was approximately 0.7 A further away from the substrate analog than the glutamate side chain. Significant differences were observed in the crystal structure of the E165D.S96P double mutant in the positions of ordered water molecules bound at the active site. The loss of two water molecules located near the side chain at position 165 was observed in isomerases containing the S96P mutation. The resulting increase in hydrophobicity of the pocket probably causes an increase in the pKa of the catalytic base, D165, thereby improving its basicity. A new ordered water molecule was observed underneath the bound PGH in the E165D.S96P structure, which likely decreases the pKa's of the substrate protons, thereby increasing their acidity. An enzyme derived carbonyl stretch at 1746 cm-1 that is only observed in the IR spectrum of the E165D.S96P double mutant isomerase with bound substrates has been assigned to a stable ground state protonated D165-enediol(ate) intermediate complex. Thus, the gain in activity resulting from the S96P second site change probably results from a combination of improving the basicity of the enzyme, improving the acidity of the substrate protons, and stabilization of a reaction intermediate. All three of these effects seem to be caused by changes in bound water molecules.

Animals↗

Rat growth hormone gene introns stimulate nucleosome alignment in vitro and in transgenic mice.

Average hepatic expression (mRNA per cell per gene) of a metallothionein-rat growth hormone (rGH) gene with its natural introns was about 15-fold higher than an intronless version when tested in transgenic mice. We examined the idea that intron removal leads to an alteration in chromatin structure that might be responsible for this effect. Using an in vitro chromatin assembly system, we observed that nucleosomes were aligned in a characteristic ordered array over the gene and promoter when all introns were present. Linker histones were necessary for this alignment to occur. In contrast, nucleosome alignment was perturbed in constructs lacking some or all of the introns. A similar disruption of nucleosome alignment was observed when comparing chromatin from livers of transgenic mice carrying rGH transgenes with or without introns. In vitro, sequences at the 3' end of the rGH gene position nucleosomes and facilitate nucleosome alignment upstream; however, nucleosome alignment does not occur on the approximately 3 kb of downstream flanking rat sequence. These observations suggest that signals present in genomic rGH DNA may serve to establish appropriate nucleosome alignment during development and, possibly, to restore nucleosome alignment to the transcribed region after disruption incurred by the passage of an RNA polymerase molecule, thereby facilitating subsequent rounds of transcription.

Animals↗

Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2.

One of the membrane guanylyl cyclases (GCs), RetGC, is expressed predominantly in photoreceptors. No extracellular ligand has been described for RetGC, but it is sensitive to activation by a soluble 24-kDa protein (p24) and is inhibited by Ca2+. This enzyme is, therefore, thought to play a role in resynthesizing cGMP for photoreceptor recovery or adaptation. By screening a human retinal cDNA library at low stringency with the cytoplasmic domains from four cyclases, we cloned cDNAs encoding a membrane CG that is most closely related to RetGC. We have named this GC RetGC-2, and now term the initially described RetGC RetGC-1. By in situ hybridization, mRNA encoding RetGC-2 is found only in the outer nuclear layer and inner segments of photoreceptor cells. By using synthetic peptide antiserum specific for each RetGC subtype, RetGC-2 can be distinguished from RetGC-1 as a slightly smaller protein in immunoblots of bovine rod outer segments. Membrane GC activity of recombinant RetGC-2 expressed in human embryonic kidney 293 cells is stimulated by the activator p24 and is inhibited by Ca2+ with an EC50 value of 50-100 nM. Our data reveal a previously unappreciated diversity of photoreceptor GCs.

Amino Acid Sequence↗

NusA interferes with interactions between the nascent RNA and the C-terminal domain of the alpha subunit of RNA polymerase in Escherichia coli transcription complexes.

The effects of NusA on the RNA polymerase contacts made by nucleotides at internal positions in the nascent RNA in Escherichia coli transcription complexes were analyzed by using the photocrosslinking nucleotide analog 5-[(4-azidophenacyl) thio]-UMP. It was placed at nucleotides between +6 and +15 in RNA transcribed from the phage lambda PR' promoter. Crosslinks of analog in these positions in RNAs which contained either 15, 28, 29, or 49 nt were examined. Contacts between the nascent RNA and proteins in the transcription complex were analyzed as the RNA was elongated, by placing the crosslinker nearest the 5' end of the RNA 10, 23, 24, or 44 nt away from the 3' end. The beta or beta' subunit of polymerase, and NusA when added, were contacted by RNA from 15 to 49 nt long. When the upstream crosslinker was 24 nt from the 3" end of the RNA (29-nt RNA), alpha was also contacted in the absence of NusA. The addition of NusA prevented RNA crosslinking to alpha. When the crosslinker was 44 nt from the 3' end (49-nt RNA), alpha crosslinks were still observed, but crosslinks to beta or beta' and NusA were greatly diminished. RNA crosslinking to alpha, and loss of this crosslink when NusA was added, was observed in the presence of NusB, NusE, and NusG and when transcription was carried out in the presence of an E. coli S100 cell extract. Peptide mapping localized the RNA interactions to the C-terminal domain of alpha.

Bacterial Proteins↗

NusA contacts nascent RNA in Escherichia coli transcription complexes.

We have examined the interaction between NusA and the nascent RNA in Escherichia coli transcription complexes on four different templates. Photocrosslinking CTP and UTP analogs were incorporated internally and at the 3' end of the RNA. Identical templates with and without boxA sequences were compared. We found that NusA did not contact the ten nucleotides nearest to the 3' end of the RNA in complexes containing RNA up to 20 nucleotides long. Longer RNA did crosslink to NusA with all four templates examined, however. We reported that RNA 80 nucleotides long from the bacteriophage T7 A1 promoter substituted in two RNA stem-loops with photocrosslinking UMP analogs did not crosslink to NusA, even though interaction between NusA and the transcription complex were demonstrated. Here, we report that when this same RNA is substituted at CMP residues, it does crosslink to NusA. Templates containing the E. coli ribosomal RNA promoter rrnG P2, with and without a boxA sequence downstream, were compared. Long RNAs from both crosslinked to NusA, and thus boxA RNA sequences are not required for interaction with NusA. NusA did not interact with the free RNA containing boxA once released from the transcription complex, nor did it interact with RNA in a binary complex containing only RNA polymerase and RNA, without the DNA template.

Bacterial Proteins↗

Prostatic non-Hodgkin's lymphoma causing acute urinary retention in childhood.

An 8-year-old boy presented with dysuria and acute retention of urine. Rectal examination showed a hard mass arising from the prostate. CT scan of the pelvis confirmed the presence of a large prostatic tumor causing bladder outflow obstruction. A provisional diagnosis of pelvic sarcoma was initially made. Biopsy of the tumor mass however, revealed non-Hodgkin's lymphoma of T-cell type. The tumor showed very good response to chemotherapy and the urinary obstruction significantly improved with a week after starting therapy.

Acute Disease↗

Ligation of the thoracic duct without thoracotomy as an effective treatment for postoperative chylothorax: a newly designed surgical procedure.

We describe herein a newly designed surgical procedure for ligating the thoracic duct to treat postoperative chylothorax, without performing a thoracotomy. This technique was successfully performed on a 50-year-old man who developed chylothorax following resection of carcinoma of the esophagus whose case is briefly presented. The advantages of this procedure include the following: the integrity of the thorax is maintained, there is less traumatization, the need for a drainage tube is eliminated, shorter hospitalization is required, and the thoracic duct is much more easily exposed than by conventional transthoracic approaches. No similar report was found in our research of the literature.

Chylothorax↗

Bacterial contaminated breast milk and necrotizing enterocolitis in preterm twins.

A pair of preterm twins developed fatal necrotizing enterocolitis (NEC) in association with Staphylococcus epidermidis septicaemia after receiving contaminated expressed breast milk (EBM). S. epidermidis NEC can be associated with severe bowel inflammation, high morbidity and mortality. Breast milk is the most suitable nutrient for preterm infants but EBM should undergo regular screening for bacterial overgrowth. We urge caution before administering EBM found to be heavily contaminated with S. epidermidis to preterm infants.

Bacteremia↗

Identification of selective immunoglobulin a deficiency by renal biopsy.

We report three cases of selective immunoglobulin A (IgA) deficiency in which lack of direct immunofluorescent staining for IgA on renal biopsy specimens contributed to the diagnosis. In two patients, one with systemic lupus erythematosus and the other having asthma with nephrotic syndrome, the diagnosis of IgA deficiency was suggested by the complete absence of IgA on the renal biopsy. In the third patient, a renal transplant recipient, initial biopsies demonstrated donor-derived IgA, which disappeared on subsequent biopsies. The diagnosis of IgA deficiency was confirmed in all three patients by serologic quantification of IgA.

Adolescent↗

Psychosocial work characteristics and cardiovascular disease risk factors in young adults: the CARDIA study. Coronary Artery Risk Disease in Young Adults.

The associations of high job demands, low decision latitude and job strain with cardiovascular disease (CVD) risk factors among 2665 black and white working men and women were examined in the Coronary Artery Risk Development in Young Adults study--a large, prospective, multi-center study of the development of CVD risk factors in young adults aged 18-30 years at baseline (1985-1986). Multiple linear and multiple logistic regression were used in cross-sectional analyses to examine the associations of job demands, decision latitude and job strain with blood pressure, total serum cholesterol, alcohol use and cigarette consumption. Inverse associations with risk factors were found for high job demands, low decision latitude and job strain. Few associations supported the hypotheses that high job demands, low decision latitude or job strain are associated with increased levels of CVD risk factors. We discuss possible explanations for these findings, including methodologic, age and gender differences between studies. In addition, we discuss the validity of job strain measures for women and minority workers.

Adolescent↗

Cardiac function in smokers and nonsmokers: the CARDIA study. The Coronary Artery Risk Development in Young Adults Study.

OBJECTIVES: This study assessed clinical and echocardiographic measures of cardiac function at rest in smokers and nonsmokers to determine the associations of cigarette smoking with various measures of left and right ventricular performance. BACKGROUND: Whereas the immediate cardiovascular effects of cigarette smoking have been well described, the long-term effects in an otherwise healthy cohort have not. Of particular interest were associations with heart rate, left ventricular end-systolic stress and left ventricular mass because higher levels of these measures would suggest increased myocardial oxygen consumption. METHODS: In year 5 of the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3,366 smokers and nonsmokers (ex-smokers were excluded) underwent echocardiography as well as assessment of heart rate, anthropometric measurements and blood pressure. Participants ranged in age from 23 to 35 years and were equally distributed by race and gender. Echocardiographic measures included pulsed Doppler pulmonary artery acceleration time (a decrease suggests increased pulmonary artery pressure), left ventricular mass, left ventricular end-systolic stress and left ventricular fractional shortening. RESULTS: All comparisons were between smokers and nonsmokers. Heart rate at rest was significantly higher in smokers by 1.5 to 5 beats/min in all race/gender groups except black men. In men who smoked, pulmonary artery acceleration time was significantly lower by 4 to 8 ms. Except for black male smokers, there was a trend toward increased left ventricular mass (3 to 8 g) in all race/gender groups, significant in black women. Left ventricular end-systolic stress was significantly higher in women who smoked (4 to 6 dynes/cm2). There were no differences for systolic blood pressure or left ventricular fractional shortening. CONCLUSION: In an assessment of cardiovascular function at rest in young adults, quantifiable differences between smokers and nonsmokers that predict increased rest myocardial oxygen consumption in smokers were found. Some of these differences were gender specific.

Adolescent↗

Expression of stress proteins and lymphocyte reactivity in heterotopic cardiac allografts undergoing cellular rejection.

This report addresses the concept that, during rejection, the allograft undergoes a stress response which leads to an increased expression of stress proteins, also called heat shock proteins (hsp), and the recruitment and activation of hsp-reactive lymphocytes. Recent studies in our laboratory have provided evidence that hsp-reactive T-cells are present in cardiac allografts undergoing rejection. In this study, an MHC incompatible heterotopic heart allograft model (ACI into LEW) was chosen to analyse the kinetics of hsp expression during the development of rejection. Allografts and syngrafts (LEW into LEW) were harvested every day during the first 5 days post-transplant. Immunoblot analysis of proteins extracted from graft stromal tissues was done with murine monoclonal antibodies (mAb) against various mammalian hsp. Proliferation studies were done to determine hsp reactivity of graft-infiltrating lymphocytes on different days post-transplant. Three types of stressful stimuli appeared to increase hsp expression in the allograft. The first was a physiological stress secondary to the trauma of the transplant procedure and ischaemia/reperfusion injury and this would occur in allogeneic and syngeneic grafts. During the first day after transplantation, both types of grafts showed higher expression of hsp72 and grp78 and to a lesser extent, hsp60 and grp75. On the second and third day, the expression of grp78 and grp96 was higher in allografts than in syngrafts and this may reflect an immunologically mediated stress response in the allograft when infiltrating hsp-reactive lymphocytes became first detectable in the allograft. The third type of stress appeared related to the inflammatory process associated with rejection. On the fourth and fifth day post-transplant, the allografts showed strong expression of at least five proteins of lower molecular mass reacting with hsp-specific mAbs; namely, approximately 40 kDa (detected by anti-hsp60), approximately 30 kDa (by anti-hsp72), approximately 45 kDa and approximately 32 kDa (by anti-hsp72 + hsc73), and approximately 50 kDa (by anti-grp78). At that time, the allograft began to show progressive inflammatory changes and tissue damage. The appearance of lower molecular mass hsp-crossreactive proteins might reflect a degradation of hsps which had increased expression earlier during the post-transplant period. This process may generate large quantities of hsp-derived peptides which may be presented by MHC molecules to graft-infiltrating T-cells. Another interpretation of the strong expression of lower molecular bands in later allografts is that they represent other stress proteins that crossreact with antibodies against hsp60 and hsp70 family members.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗