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Biomedical subjects

K Liu

Publications and source records attributed to K Liu.

At least 307 records · Page 17Linked to original sources

Role of Escherichia coli RNA polymerase alpha subunit in modulation of pausing, termination and anti-termination by the transcription elongation factor NusA.

The alpha subunit (alpha) of RNA polymerase (RNAP) is critical for assembly of polymerase and positive control of transcription initiation in Escherichia coli. Here, we report that alpha also plays a role in transcription elongation, and this involves a direct interaction between alpha and NusA factor. During in vitro transcription without NusA, alpha interacts with the nascent RNA, as revealed by photocrosslinking. When NusA is present, RNA crosslinks to NusA rather than to alpha. We show that this NusA-RNA interaction is diminished during transcription with an RNAP mutant that lacks the C-terminus of alpha beyond amino acid 235, including the so-called alpha CTD. The absence of alpha CTD also affects NusA's ability to enhance transcription pausing, termination at intrinsic terminators and anti-termination by the phage lambda Q anti-terminator, but not anti-termination by the lambda N anti-terminator. NusA functions are not recovered even when transcription with mutant RNAP is done with excess NusA, a condition which does restore NusA-RNA crosslinking. By affinity chromatography, we show that NusA interacts directly with alpha, and also with beta and beta', but not with mutant alpha. Hence, alpha-NusA interaction is vital for the control of transcript elongation and termination.

Bacterial Proteins↗

Blood pressure in young blacks and whites: relevance of obesity and lifestyle factors in determining differences. The CARDIA Study. Coronary Artery Risk Development in Young Adults.

BACKGROUND: Middle-aged black men and women have higher blood pressure, on average, than whites. However, this pattern is inconsistent in children and adolescents. This study explores how differences in lifestyle factors in young adulthood may influence blood pressure patterns in the two races. METHODS AND RESULTS: The Coronary Artery Risk Development in Young Adults (CARDIA) study is an ongoing collaborative investigation of lifestyle and the evolution of cardiovascular disease risk factors in a random sample of young adults ages 18 to 30 years at baseline (1985 to 1986). Data from four examinations over 7 years were analyzed with the use of a method that simultaneously examined cross-sectional and longitudinal relationships of lifestyle factors and blood pressure. This study included 1154 black women, 853 black men, 1126 white women, and 1013 white men. Blacks had higher systolic blood pressure and diastolic blood pressure than whites at every examination. Racial differences were much greater in women than in men and increased over time. Within each sex-race group, average diastolic blood pressure over four examinations was positively associated with baseline age, body mass index, and alcohol intake and negatively associated with physical activity, cigarette use, and intake of potassium and protein. Longitudinal change in diastolic blood pressure was positively associated with changes in body mass index and alcohol intake. After adjustment for obesity and other lifestyle factors, black-white diastolic blood pressure differences were reduced substantially: 21% to 75% for men and 49% to 129% for women. Results for systolic blood pressure were similar. CONCLUSIONS: Differences in obesity and other lifestyle factors in young adults largely explain the higher baseline blood pressure and greater increase over time of blacks relative to whites.

Adolescent↗

Structure of Py.Pu.Py DNA triple helices. Fourier transforms of fiber-type x-ray diffraction of single crystals.

Well-formed hexagonal crystals of oligomeric DNA triple helices exhibit fiber-type x-ray diffraction patterns [cf., Liu et al. (1994) Nature Struct. Biol. 1, 11], which can be interpreted in terms of Fourier transforms of these helices. Precession photographs of a triplex formed of dA and dT chains show that it has 13 residues per turn. In contrast, a sequence containing the four natural bases A, G, C, and T has 12 residues per turn. In this sense the triple helices exhibit a sequence-dependent polymorphism, though both have C2'-endo sugar pucker and B rather than A conformation. New models are constructed, using constraints from x-ray diffraction, and Fourier transforms of the models are calculated. Good agreement in the amplitudes and positions of the calculated and observed diffraction intensities confirms the structures for both triple helices. These are the first stereochemically satisfactory DNA triple helices for which coordinates based on adequate experimental data were provided. Sequences for crystallization are designed to achieve unique base alignments and are screened for the presence of sharp bands on gel electrophoresis to assure the absence of multiple species caused by strand slippage. Despite intensive efforts to observe normal crystal diffraction by varying sequences and conditions, all crystals exhibited only fiber-type diffraction. We suggest that this behavior may be an intrinsic property of triple helices and discuss possible reasons for the results. Spectroscopic and chemical experiments establish that the oligonucleotides exist in solution as triple helices under the conditions of crystallization.

Computer Simulation↗

Gouty tophus presenting as a soft-tissue mass diagnosed by fine-needle aspiration: a case report.

We present a case in which a primary diagnosis of gout was made by fine-needle aspiration. The patient had a right distal ulnar mass, and the initial clinical and radiological diagnoses were that of giant cell tumor of tendon sheath. While tophi are the hallmark of gout, they rarely undergo aspiration because of the known clinical history. This case demonstrates that a tophus may mimic a soft-tissue neoplasm. Whenever an aspiration yields amorphous or granular material, the cytopathologist should be aware of and consider gouty tophus as a diagnostic possibility and perform compensated polarized microscopy on the specimen smears.

Aged↗

Study of chronic lymphocytic leukemia cells by FT-IR spectroscopy and cluster analysis.

The peripheral mononuclear cells from 23 normal individuals and the purified B cells from 38 patients with chronic lymphocytic leukemia (CLL) were examined by Fourier transform infrared (FT-IR) spectroscopy. Differences were observed between the CLL and normal cells at the DNA, protein and lipid levels, with CLL cells having greater DNA and lower lipid contents than normal cells. In addition, the spectral character of the CLL and normal cells varied, demonstrating that there were also qualitative differences in the DNA and lipids. Statistical analysis, based on hierarchical clustering, separated normal from CLL cells completely and classified them into two subgroups for normal cells, while the CLL cells could be divided into three subgroups that were distinct from the normal cells. These differences were based on the lipid and DNA content and the overall spectral character of the cells.

B-Lymphocytes↗

Accurate velocity mapping with FAcE.

Spin dislocation between the slice selection, phase encoding, and frequency encoding is a source of image distortions. Two strategies can be pursued to improve the appearance of moving spins in an image. Either the sequence is made equally sensitive to velocity-dependent dislocation artifacts for all spatial directions or the sensitivity is reduced with a shorter echo time. The first approach increases the dislocation for the phase-encoding direction and is therefore not useful if velocity maps with minimal distortion are the goal. FAcE (FID acquired echoes) is a sequence with separate sampling of the left and right k-space half-planes that allows for very short echo times. It was applied for velocity mapping of flow in the slice select direction. Special attention was paid to a compact design of the velocity-encoding select gradient to achieve short echo times even with high velocity sensitivity. Artifacts introduced by in-plane motion were studied for FAcE and conventional gradient-echo sequences, both in phantom experiments and simulation. FAcE allows for very short echo times with inherent motion compensation of the frequency-encoding gradient. Thus, both motion-related dislocation artifacts and signal voids due to coherence loss in regions with irregular flow are minimal.

Artifacts↗

Seven-year trends in plasma low-density-lipoprotein-cholesterol in young adults: the CARDIA Study.

To identify determinants of recent secular trends in lipids and characterize their influence on age-related increases in LDL-cholesterol, we examined a cohort of black and white men and women aged 18-30 in 1985-1986. Secular trends were determined by comparing participants aged 25-30 at baseline with those aged 25-30 at year 7 (2788 and 1395 participants, respectively). LDL-cholesterol was lower among those 25-30 at year 7 (5.9 to 10.2 mg/dL, depending on race-sex group; P < 0.001); weight was higher (8.3 to 12.5 lb; P < 0.001); Keys score was lower (-4.2 to -7.3 units; P < 0.001); and use of oral contraceptives was greater (white women only, P < 0.01). Among 4086 participants followed for 7 years, LDL-cholesterol changed little or decreased, despite substantial weight increases in all groups (11.6 to 19.0 lb; P < 0.001). Keys scores decreased by 6.1 to 8.0 units, and use of oral contraceptives decreased (P < 0.001). Declining secular trends in LDL-cholesterol occurred despite upward trends in weight; the decline was associated with lower dietary fat and cholesterol and offset expected age-related increases in LDL-cholesterol.

Adult↗

Psychological long-term effects of sterilization on anxiety and depression.

Two-thousand cases (500 women and 500 men with sterilization; 500 women and 500 men without sterilization) in two counties and two cities in Sichuan, China, were investigated between 15 September 1992 and 30 April 1993. Information was obtained about their age, parity, marriage, contraceptives, social behavior, and present psychological characteristics. CES-D, SAS, and E.P.Q. scales were used to assess the depressive symptomatology, anxiety, and personality of the subjects. The results revealed that sterilization psychologically affected the depressive symptoms and anxiety under the neutral personality. In addition, depressive symptoms and anxiety were related to the subjects' age, educational level, income, operative doctors' attitudes to sterilization acceptors, and subjects' understanding of the sterilization.

Adult↗

Changes in keratinocyte differentiation during accelerated repopulation of the irradiated mouse epidermis.

Epidermal stem cells accelerate their repopulation rate during fractionated irradiation. To study the changes in keratinocyte differentiation associated with radiation-induced repopulation, we investigated the expression of a panel of 14 monoclonal or polyclonal antibodies against keratins, involucrin and others, as well as the expression of 15 lectins in the irradiated mouse leg skin. Tissue samples were collected after 1, 2, and 3 weeks of daily irradiation with 3 Gy per fraction. Abnormal morphological appearance of the irradiated epidermis suggested disturbed terminal differentiation. Keratin 16 (K16) was negative in normal epidermis but intense staining was observed in the irradiated epidermis. Involucrin was expressed in the outmost suprabasal layers only in the normal epidermis but extended to the lower layers in the irradiated epidermis. The lectin binding patterns for agglutinins from Soybean, Dolichos biflorus, and Helix pomatia showed differences between the normal and the irradiated epidermis. From these characteristic changes in staining patterns we concluded that accelerated repopulation of the epidermis during fractionated irradiation is associated with a deficiency in terminal squamous differentiation.

Animals↗

Preliminary studies on the role of plasminogen activator in seminal plasma of human and rhesus monkey.

Two types of plasminogen activators (PA), tissue type (tPA) and urokinase type (uPA), were identified in the seminal plasma of both the human and the rhesus monkey. We studied the possible relationship between PA activities in the seminal plasma and the sperm counts and motility and demonstrated that: (i) PA activity in human seminal plasma from infertile patients was associated with immotile spermatozoa; (ii) the treatment of fertile men with testosterone enanthate (TE) to induce azoospermia was accompanied by an increase in seminal PA activity; (iii) when monomer T4 (isolated from multiglycosides of Tripterygium wilforddi) was administered to fertile male rhesus monkeys to induce azoospermia, PA activities in seminal plasma increased considerably; and (iv) immunocytochemistry studies showed that both uPA and PAI-1 antigens were localized on the surface of human spermatozoa, indicating that human spermatozoa were capable of binding uPA and PAI-1 through their receptors or forming a complex. These data demonstrate that seminal PA activity may be related to azoospermia, and possibly, to the fertilizing capability of spermatozoa in primates.

Adult↗

Effects of pre- and postischemic administration of thiopental on transmitter amino acid release and histologic outcome in gerbils.

BACKGROUND: The mechanism by which barbiturates protect neurons against ischemia is unclear, particularly when they are given after ischemia or reperfusion begins. Because an excess release of excitatory neurotransmitters causes postsynaptic membrane depolarization, which triggers neuronal damage in ischemia, the effects of thiopental on histologic outcome, ischemia-induced amino acid release, and anoxic depolarization in gerbils were studied. METHODS: The effects of different doses of thiopental administered before or after ischemia were examined morphologically by assessing delayed neuronal death in hippocampal CA1 pyramidal cells produced by forebrain ischemia for 3 min in gerbils. The ischemia-induced changes in output of aspartate, glutamate, glycine, taurine, and gamma-aminobutyric acid were measured using a microdialysis-high-performance liquid chromatography procedure, and the differences among a halothane-anesthetized group, a thiopental-administered group, and a group given thiopental after a period of ischemia were evaluated. The changes induced in the direct-current potential in the hippocampal CA1 area by forebrain ischemia were compared in animals anesthetized with halothane and those given thiopental. RESULTS: Preischemic administration of thiopental at all doses decreased the risks for delayed neuronal death (P < 0.01). Post-ischemic administration at a dosage of 2 mg.kg-1.min-1 for 60 min protected neurons, but the same dose for 10 min did not ameliorate the cell injury. Forebrain ischemia produced marked increases in all amino acids 3 to 6 min after the start of recirculation in the halothane-anesthetized gerbils, whereas thiopental anesthesia (2 mg.kg-1.min-1) reduced these increases throughout the experimental period, except for glycine (P < 0.01). The initiation of thiopental after reflow did not markedly diminish these increases. Thiopental anesthesia prolonged the onset of anoxic depolarization and reduced its maximal amplitude. CONCLUSIONS: Thiopental helps protect the brain from ischemia, although treatment with this agent after ischemia requires a larger dose than that before ischemia. The effect of preischemic treatment may be related to the suppression of the excitatory amino acid release and the direct-current potential shift.

Animals↗

Relationships between depressive symptoms, anxiety, alcohol consumption, and blood pressure: results from the CARDIA Study. Coronary Artery Risk Development in Young Adults Study.

OBJECTIVES: We examined cross-sectional relationships among depressive symptoms, anxiety, alcohol intake, and blood pressure. Test hypotheses were that: (1) alcohol intake, depressive symptoms, and anxiety would be positively related to blood pressure; (2) depressive symptoms and anxiety would have a stronger association with alcohol intake in Blacks than in Whites; and (3) adjustment for differences in depressive symptoms, anxiety, and alcohol intake would reduce Black-White blood pressure differences. METHODS: Study hypotheses were tested in a sample of 4,352 Black and White adults, participating in the CARDIA study. Hypotheses were tested using multiple linear regression. RESULTS: Alcohol intake was positively related to systolic (p = 0.0001) and diastolic (p = 0.0004) blood pressure in men, but not in women. Depressive symptoms and anxiety were unrelated to blood pressure. The relationship between alcohol intake and depressive symptoms differed by race/ethnicity in men (p = 0.0719) and in women (p = 0.0002). Alcohol intake increased with increasing levels of depressive symptoms, but the increase was greater in Blacks than in Whites. After accounting for alcohol intake, body mass index, and other variables, Black-White blood pressure differences were reduced in men, but not in women; most of the reduction was caused by body mass index. CONCLUSIONS: Blacks may respond differently than Whites to psychological distress.

Adolescent↗

Fatal haemorrhagic gastritis associated with oral sulindac treatment for patent ductus arteriosus.

We report the first case in a preterm infant given oral sulindac for treatment of symptomatic patent ductus arteriosus who subsequently developed severe acute haemorrhagic gastritis leading to disseminated intravascular coagulation, massive pulmonary haemorrhage and death. The postmortem examination suggested that the mechanism was likely a direct irritant insult causing ischaemia on the gastric mucosa. Although sulindac is supposed to be a renal-sparing non-steroidal anti-inflammatory prodrug associated with minimal renal and gastrointestinal adverse effects, clinicians should be alerted to this potential life-threatening complication in preterm infants. Until the question of safety could be adequately addressed, the use of sulindac for ductal closure should remain experimental.

Cyclooxygenase Inhibitors↗

C/EBPbeta is a negative regulator of human papillomavirus type 11 in keratinocytes.

We have evaluated the impact of the CCAAT enhancer-binding protein (C/EBP) transcription factors on human papillomavirus type 11 (HPV11). C/EBPbeta is in nuclei of cultured foreskin keratinocytes and binds its consensus sequence in HPV11 DNA. We have used the novel approach of depleting the availability of C/EBPs in vivo using nuclease-resistant oligomers containing C/EBP DNA binding sites. In cultured foreskin keratinocytes containing replicating HPV11 DNA, levels of both HPV11 transcripts and HPV DNA increase after treatment with oligomers; containing the C/EBPbeta DNA binding motif. These results indicate that C/EBPbeta is a repressor for HPV11 in keratinocytes.

Base Sequence↗

Cloning and characterization of a highly repeated DNA sequence in Hordeum vulgare L.

A novel repetitive DNA sequence, R10hvcop, has been identified in the barley (Hordeum vulgare L.) genome. This 830 base pair (bp) DNA sequence has a 606-bp open reading frame and is present as approximately 1.96 x 10(5) copies per haploid barley genome. Southern blot analysis revealed that repetitive DNA elements containing R10hvcop and related sequences were dispersed within the barley chromosomes. Sequences similar to R10hvcop were also found in wheat (Triticum aestivum L.), rye (Secale cereale L.), and oat (Avena sativa L.) with copy numbers of 8 x 10(4), 1.39 x 10(5), and 7.9 x 10(4) per haploid genome, respectively. Sequences similar to R10hvcop were also present in the corn (Zea mays L. ssp. mays) genome, but they were not highly repeated. Barley, wheat, rye, oat, and corn showed species-specific restriction fragment length polymorphisms of R10hvcop and related sequences. Computer-based similarity searches revealed that R10hvcop is closely related to reverse transcriptase genes in retrotransposon-like elements of several plant species and of Drosophila. The highly repetitive nature, interspersed distribution, and high degree of similarity to reverse transcriptase genes suggests that R10hvcop contains the sequence of a diverged reverse transcriptase gene.

Base Sequence↗

Coordinated and cell-specific induction of both physiological plasminogen activators creates functionally redundant mechanisms for plasmin formation during ovulation.

Several lines of indirect evidence indicate that plasmin-mediated proteolysis plays a role in the breakdown of the follicle wall during ovulation. Consistent with this, the ovulation efficiency of mice lacking the two known physiological plasminogen activators (PAs), tissue-type PA (tPA) and urokinase-type PA (uPA), is reduced by 26%. Surprisingly, mice with a single deficiency of either tPA or uPA gene function were normal in their capacity to ovulate. In this study we used in situ hybridization and casein in situ zymography to localize the expression of messenger RNAs (mRNAs) encoding PAs and PA inhibitors and to examine the net PA activity in the mouse ovary at the time of ovulation. Although uPA mRNA expressed by granulosa cells is the most abundant and dramatically up-regulated PA before ovulation, a previously unnoticed coordinated induction oftPA mRNA was found in thecal-interstitial tissue. The existence of redundant mechanisms for plasmin production in the ovary may be the cause of the normal ovulation efficiency in single deficient mice lacking tPA or uPA. The expression of mRNAs for PA inhibitors, types 1 and 2, was low in the ovary, with minor inductions at restricted time points. In contrast, expression of protease nexin-1 (PN-1) by granulosa cells was high during the entire periovulatory period. Among subpopulations of granulosa cells, the expression of PN-1 and uPA was heterogeneous and complementary. Cumulus cells expressed high levels of PN-1 mRNA and low levels of uPA mRNA, thereby providing an inhibitory activity that may protect the mucified matrix of the cumulus oocyte complex from proteolytic degradation.

Amyloid beta-Protein Precursor↗

Coordinated expression of tissue-type plasminogen activator and plasminogen activator inhibitor type 1 during corpus luteum formation and luteolysis in the adult pseudopregnant rat.

Proteolytic activity generated by the plasminogen activator (PA) system is associated with many biological processes. Using an adult pseudopregnant rat model, we have studied how two components of the PA system, tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1), are expressed temporally and spatially during different developmental stages of the corpus luteum (CL). Northern blot analysis, in situ hybridization, in situ zymography, and fibrin overlay were used to analyze the expression and distribution of tPA and PAI-1 messenger RNA (mRNA) as well as PA activity in CL of different ages. We demonstrated that during the luteinization period (approximately days 1-2), tPA mRNA was highly and evenly expressed in newly formed CL, whereas PAI-1 mRNA was mainly detected in the central part of the same CL. In accordance with these findings, proteolytic activity generated by tPA was detected in the outer region of newly formed CL by in situ zymography. During the luteotropic period (approximately days 3-10), tPA mRNA expression was very low. PAI-1 mRNA expression was also low, but increased on day 10. As expected, proteolytic activity was very low during this period. During functional luteolysis (days 13-14) and subsequent structural luteolysis, tPA mRNA was elevated. PAI-1 mRNA was also expressed during this period. Moreover, the net PA activity, as determined by fibrin overlay, was relatively high during this period. Our studies indicate that tPA and PAI-1 are coordinately expressed in the CL, resulting in increased proteolytic activities during the luteinization and luteolytic periods. PA-mediated proteolysis may, therefore, play a role in both CL formation and luteolysis in rats.

Animals↗

Virtual bronchoscopy. Relationships of virtual reality endobronchial simulations to actual bronchoscopic findings.

Advances in computer technology have permitted development of virtual reality images of the tracheobronchial tree using data sets derived from helical CT of the chest. To determine the relevance of these images to actual bronchoscopic findings, we compared "virtual bronchoscopy" images with videotaped bronchoscopy results in 20 patients who had undergone both helical chest CT and fiberoptic bronchoscopy during clinical evaluation of their thoracic problems. Suboptimal endobronchial simulations in ten patients identified important, readily-addressed technical requirements for this imaging procedure. In the ten patients with technically suitable renderings of the airway, virtual bronchoscopy simulations accurately demonstrated endobronchial obstructions by tumor in five, airway distortion and/or ectasia in four, and accessory bronchi in another. These preliminary observations suggest that virtual bronchoscopy simulations accurately represent major endobronchial anatomic findings. This technique may have a role in prebronchoscopy planning, endoscopy training, and/or endobronchial therapy, and merits further study.

Bronchial Diseases↗