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Biomedical subjects

H Liu

Publications and source records attributed to H Liu.

At least 595 records · Page 33Linked to original sources

Cardiopulmonary dysfunction in cirrhosis.

Cirrhosis is associated with several circulatory abnormalities. These include hyperkinetic systemic and splanchnic circulation, hepatopulmonary syndromes including pulmonary hypertension, and cirrhotic cardiomyopathy. Hepatopulmonary syndrome generally refers to hypoxaemia seen in patients with chronic liver disease and appears to be relatively common, although often subclinical. However, significant pulmonary hypertension occurs in 0.2-0.7% of cirrhotic patients. Nitric oxide and/or other vasodilators appear to be involved in the pathogenesis of hepatopulmonary syndrome through induction of pulmonary capillary dilatation which increases the alveolar-arterial oxygen gradient. Cirrhotic cardiomyopathy refers to abnormal left ventricular function which is manifested under conditions of physiological or pharmacological stress. The emergence of liver transplantation as an effective treatment for end-stage liver disease has led to recognition of previously subclinical cardiomyopathy and congestive heart failure accounts for significant morbidity and mortality after this procedure. Diminished myocardial beta-adrenergic receptor function has been shown to play an important role in the pathogenesis of this condition. The contributions of other factors including nitric oxide, catecholamines and membrane fluidity changes are under investigation. Cirrhotic patients also have an increased incidence of other cardiac abnormalities, such as endocarditis and pericardial effusions.

Animals↗

Isolation of 10 differentially expressed cDNAs in differentiated Neuro2a cells induced through controlled expression of the GD3 synthase gene.

Recently, we showed that transfection of GD3 synthase cDNA into Neuro2a cells, a mouse neuroblastoma cell line, causes cell differentiation with neurite sprouting. In a search for the genes involved in this ganglioside-induced Neuro2a differentiation, we used a tetracycline-regulated GD3 synthase cDNA expression system combined with differential display PCRs to identify mRNAs that were differentially expressed at four representative time points during the process. We report here the identification of 10 mRNAs that are expressed highly at the Neuro2a differentiated stage. These cDNAs were named GDAP1-GDAP10 for (ganglioside-induced differentiation-associated protein) cDNAs. It is interesting that in retinoic acid-induced neural differentiated mouse embryonic carcinoma P19 cells, GDAP mRNA expression levels were also up-regulated (except that of GDAP3), ranging from three to >10 times compared with nondifferentiated P19 cells. All the GDAP genes (except that of GDAP3) were developmentally regulated. The GDAP1, 2, 6, 8, and 10 mRNAs were expressed highly in the adult mouse brain, whereas all the other GDAP mRNAs were expressed in most tissues. Our results suggested that these GDAP genes might be involved in the signal transduction pathway that is triggered through the expression of a single sialyltransferase gene to induce neurite-like differentiation of Neuro2a cells.

Aging↗

Are Latinos less satisfied with communication by health care providers?

OBJECTIVE: To examine associations of patient ratings of communication by health care providers with patient language (English vs Spanish) and ethnicity (Latino vs white). METHODS: A random sample of patients receiving medical care from a physician group association concentrated on the West Coast was studied. A total of 7,093 English and Spanish language questionnaires were returned for an overall response rate of 59%. Five questions asking patients to rate communication by their health care providers were examined in this study. All five questions were administered with a 7-point response scale. MAIN RESULTS: We estimated the associations of satisfaction ratings with language (English vs Spanish) and ethnicity (white vs Latino) using ordinal logistic models, controlling for age and gender. Latinos responding in Spanish (Latino/Spanish) were significantly more dissatisfied compared with Latinos responding in English (Latino/English) and non-Latino whites responding in English (white) when asked about: (1) the medical staff listened to what they say (29% vs 17% vs 13% rated this "very poor," "poor," or "fair"; p <.01); (2) answers to their questions (27% vs 16% vs 12%; p <.01); (3) explanations about prescribed medications (22% vs 19% vs 14%; p <.01); (4) explanations about medical procedures and test results (36% vs 21% vs 17%; p <.01); and (5) reassurance and support from their doctors and the office staff (37% vs 23% vs 18%; p <.01). CONCLUSION: This study documents that Latino/Spanish respondents are significantly more dissatisfied with provider communication than Latino/English and white respondents. These results suggest Spanish-speaking Latinos may be at increased risk of lower quality of care and poor health outcomes. Efforts to improve the quality of communication with Spanish-speaking Latino patients in outpatient health care settings are needed.

Adult↗

Application of near-infrared time-resolved spectroscopy to rat liver--a preliminary report for surgical application.

The applicability of near-infrared time-resolved spectroscopy to rat liver surgery was investigated. First, the technical reliability in determining the absorption coefficient (mu(a)) and reduced scattering coefficient (mu'(s)) of the liver was checked. Next, boundary effects in determining mu(a) and mu'(s) of the rat liver were examined. Finally, changes in mu(a) and mu'(s) of rat liver with ischaemia were directly measured by TRS. Our TRS system showed that the mu(a) value held a linear correlation with the ink concentration in a lipid emulsion until mu(a) reached 1.2 cm(-1), while the mu'(s) was fairly independent. The mu(a) values of blood-free rat liver and blood-containing rat liver at 780 nm were observed to be 0.43 cm(-1) and 0.67 cm(-1) by using the matching method, indicating that TRS is reliable in determining mu(a) and mu'(s) of the liver. Possible errors in mu(a) and mu'(s) determination due to the boundary effects of the rat liver were as small as 7%, when the mu(a) value was as high as observed for the liver. The oxygen saturation of haemoglobin (SO2) was changed from 64.9% to 8.0%, and the haemoglobin content (THB) from 189.1 microM to 131.6 microM by ischaemia. Mu'(s) dynamically changed in the range 7.06 cm(-1) to 11.36 cm(-1). We conclude that time-resolved measurement is applicable in the high-mu(a) region observed in the liver, and can give quantitative estimations of SO2 and THB in the liver.

Animals↗

Saccharomyces cerevisiae G1 cyclins are differentially involved in invasive and pseudohyphal growth independent of the filamentation mitogen-activated protein kinase pathway.

Several lines of evidence suggest that the morphogenetic transition from the yeast form to pseudohyphae in Saccharomyces cerevisiae may be regulated by the cyclin-dependent kinase (Cdk). To examine this hypothesis, we mutated all of the G1 cyclin genes in strains competent to form pseudohyphae. Interestingly, mutation of each G1 cyclin results in a different filamentation phenotype, varying from a significant defect in cln1/cln1 strains to enhancement of filament production in cln3/cln3 strains. cln1 cln2 double mutants are more defective in pseudohyphal development and haploid invasive growth than cln1 strains. FLO11 transcription, which correlates with the level of invasive growth, is low in cln1 cln2 mutants and high in grr1 cells (defective in proteolysis of Cln1,2), suggesting that Cln1,2/Cdks regulate the pseudohyphal transcriptional program. Epistasis analysis reveals that Cln1,2/Cdk and the filamentation MAP kinase pathway function in parallel in regulating filamentous and invasive growth. Cln1 and Cln2, but not Ste20 or Ste12, are responsible for most of the elevated FLO11 transcription in grr1 strains. Furthermore, phenotypic comparison of various filamentation mutants illustrates that cell elongation and invasion/cell-cell adhesion during filamentation are separable processes controlled by the pseudohyphal transcriptional program. Potential targets for G1 cyclin/Cdks during filamentous growth are discussed.

Cell Division↗

Reconstruction of mouse oocytes by germinal vesicle transfer: maturity of host oocyte cytoplasm determines meiosis.

We evaluated the maturational competence of mouse oocytes reconstructed by the transfer and electrofusion of germinal vesicles (GV) into anuclear cytoplasts of GV stage oocytes (both auto- and hetero-transfers), metaphase II stage oocytes or zygotes. Following in-vitro culture, the maturation rates of the reconstructed oocytes to metaphase II did not significantly differ between auto- and hetero-transfers (40/70 versus 95/144 respectively); these rates also did not differ from those of control oocytes (57/97) which were matured in vitro without micromanipulation and electrofusion. In contrast, when a GV was transferred into an enucleated metaphase II oocyte or a zygote, only a few reconstructed oocytes underwent germinal vesicle breakdown (5/30 and 2/21 respectively); moreover, none reached metaphase II stage. Cytogenetic and immunofluorescence analyses were conducted on hetero-GV oocytes that extruded a first polar body. Each oocyte showed two groups of chromosomes, one in the cytoplast and one in the polar body, as well as a bipolar spindle with twenty univalent chromosomes. Our findings suggest that oocytes reconstructed by GV transfer into a cytoplast of the same developmental stage mature normally in vitro through metaphase II. Such oocytes may be a useful research model to elucidate the cytoplasmic and nuclear mechanisms regulating meiosis and the relationships between meiotic errors and age-related changes in the oocyte.

1-Methyl-3-isobutylxanthine↗

Maize streak virus coat protein is karyophyllic and facilitates nuclear transport of viral DNA.

Transport of maize streak virus (MSV) DNA into the nucleus of host cells is essential for virus replication and the presence of virus particles in the nuclei of infected cells implies that coat protein (CP) must enter the nucleus. To see if CP is imported into the nucleus in the absence of other viral gene products, the MSV CP gene was expressed in insect cells with a baculovirus vector system, and also in tobacco protoplasts with a cauliflower mosaic virus (CaMV) 35S promoter-driven transient gene expression vector. Immunofluorescent staining showed that the CP accumulated in the nuclei of both insect and tobacco cells. Mutagenesis of a potential nuclear localization signal in the CP resulted in cytoplasmic accumulation of the mutant protein. We have shown previously that the CP binds to single-stranded (ss) and double-stranded (ds) viral DNA. To investigate if CP might also be involved in viral DNA nuclear transport, Escherichia coli-expressed CP, together with TOTO-1-labeled viral ss or ds DNA, was microinjected into maize and tobacco epidermal cells. Both ss and ds DNA moved into the nucleus when co-injected with the CP but not with E. coli proteins alone. These results suggest that, in addition to entering the nucleus where it is required for encapsidation of the viral ss DNA, the MSV CP facilitates the rapid transport of viral (ss or ds) DNA into the nucleus.

Amino Acid Sequence↗

Brain biopsy using high-field strength interventional magnetic resonance imaging.

OBJECTIVE: Lesions within the brain are commonly sampled using stereotactic techniques. The advent of interventional magnetic resonance imaging (MRI) now allows neurosurgeons to interactively investigate specific regions, with exquisite observational detail. We evaluated the safety and efficacy of this new surgical approach. METHODS: Between January 1997 and June 1998, 35 brain biopsies were performed in a high-field strength interventional MRI unit. All biopsies were performed using MRI-compatible instrumentation. Interactive scanning was used to confirm accurate positioning of the biopsy needle within the region of interest. Intraoperative pathological examination of the biopsy specimens was performed to verify the presence of diagnostic tissue, and intra- and postoperative imaging was performed to exclude the presence of intraoperative hemorrhage. Recently, magnetic resonance spectroscopic targeting was used for six patients. RESULTS: Diagnostic tissue was obtained in all 35 brain biopsies and was used in therapeutic decision-making. Histological diagnoses included 28 primary brain tumors (12 glioblastomas multiforme, 9 oligodendrogliomas, 2 anaplastic astrocytomas, 2 astrocytomas, 1 lymphoma, and 1 anaplastic oligodendroglioma), 1 melanoma brain metastasis, 1 cavernous sinus meningioma, 1 cerebral infarction, 1 demyelinating process, and 3 cases of radiation necrosis. In all cases, magnetic resonance spectroscopy was accurate in distinguishing recurrent tumors (five cases) from radiation necrosis (one case). No patient sustained clinically or radiologically significant hemorrhage, as determined by intraoperative imaging performed immediately after the biopsy. One patient (3%) suffered transient hemiparesis after a pontine biopsy for investigation of a brain stem glioma. Another patient developed scalp cellulitis, with possible intracranial extension, 3 weeks after the biopsy; this condition was effectively treated with antibiotic therapy. Three patients were discharged on the day of the biopsy. CONCLUSION: Interventional 1.5-T MRI is a safe and effective method for evaluating lesions of the brain. Magnetic resonance spectroscopic targeting is likely to augment the diagnostic yield of brain biopsies.

Adolescent↗

Optical processing architecture and its potential application for digital and analog radiography.

In this report we introduce the fundamental architectures and the potential applications of optical processing techniques in medical imaging. Three basic optical processing architectures were investigated for digital and analog radiography. The processors consist of a module that converts either the analog or the digital radiograph into a coherent light distribution; a coherent optical processing architecture that performs various mathematical operations; a programmable digital-optical interface and other accessories. Optical frequency filters were implemented for mammographic and other clinical feature enhancement. In medical image processing, digital computers offer the advantages of programmability and flexibility. In contrast, optical processors perform parallel image processing with high speed. Optical processors also offer analog nature, compact size, and cost effectiveness. With technical advances of digital-optical interface devices, the medical image processor, in the foreseeable future, may be a hybrid device, namely, a programmable optical architecture.

Equipment Design↗

Measurement of x-ray attenuation coefficients of aqueous solutions of indocyanine green and glycated chitosan.

We report our experimental results of measurements of x-ray attenuation coefficients of aqueous solutions of a light absorbing dye, indocyanine green, and an immunoadjuvant, glycated chitosan. In the treatment of metastatic tumors in rats using a novel laser immunotherapy these solutions were administered in situ. The x-ray attenuation data of the solutions are essential to development of an x-ray digital imaging system for monitoring the administration of the solution, as well as for the distribution and the diffusion of the solution in tumors and in surrounding tissue. The composition of the solutions, the measurement system configuration, and the technique used to determine the attenuation coefficients are described. The experimental results show that glycated chitosan has a higher attenuation coefficient compared to indocyanine green and water. Our experimental data proved that, even at low concentrations, the x-ray attenuation through these aqueous solutions could be differentiated. Therefore, a digital x-ray imaging technique can be used effectively in monitoring and controlling the intratumor diffusion and distributions of these solutions.

Adjuvants, Immunologic↗

beta1-chain integrins are not essential for intimin-mediated host cell attachment and enteropathogenic Escherichia coli-induced actin condensation.

Intimin is a bacterial outer membrane protein required for intimate attachment of enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) to mammalian cells. beta1-chain integrins have been proposed as candidate receptors for intimin. We found that binding of mammalian cells to immobilized intimin was not detectable unless mammalian cells were preinfected with EPEC or EHEC. beta1-chain integrin antagonists or inactivation of the gene encoding the beta1-chain did not affect binding of preinfected mammalian cells to intimin or the actin condensation associated with the attachment of EPEC. The results indicate that beta1-chain integrins are not essential for intimin-mediated cell attachment or EPEC-mediated actin polymerization.

Actins↗

Role of crotonyl coenzyme A reductase in determining the ratio of polyketides monensin A and monensin B produced by Streptomyces cinnamonensis.

The ccr gene, encoding crotonyl coenzyme A (CoA) reductase (CCR), was cloned from Streptomyces cinnamonensis C730.1 and shown to encode a protein with 90% amino acid sequence identity to the CCRs of Streptomyces collinus and Streptomyces coelicolor. A ccr-disrupted mutant, S. cinnamonensis L1, was constructed by inserting the hyg resistance gene into a unique BglII site within the ccr coding region. By use of the ermE* promoter, the S. collinus ccr gene was expressed from plasmids in S. cinnamonensis C730. 1/pHL18 and L1/pHL18. CCR activity in mutant L1 was shown to decrease by more than 90% in both yeast extract-malt extract (YEME) medium and a complex fermentation medium, compared to that in wild-type C730.1. Compared to C730.1, mutants C730.1/pHL18 and L1/pHL18 exhibited a huge increase in CCR activity (14- and 13-fold, respectively) in YEME medium and a moderate increase (3.7- and 2. 7-fold, respectively) in the complex fermentation medium. In the complex fermentation medium, S. cinnamonensis L1 produced monensins A and B in a ratio of 12:88, dramatically lower than the 50:50 ratio observed for both C730.1 and C730.1/pHL18. Plasmid (pHL18)-based expression of the S. collinus ccr gene in mutant L1 increased the monensin A/monensin B ratio to 42:58. Labeling experiments with [1, 2-(13)C(2)]acetate demonstrated the same levels of intact incorporation of this material into the butyrate-derived portion of monensin A in both C730.1 and mutant C730.1/pLH18 but a markedly decreased level of such incorporation in mutant L1. The addition of crotonic acid at 15 mM led to significant increases in the monensin A/monensin B ratio in C730.1 and C730.1/pHL18 but had no effect in S. cinnamonensis L1. These results demonstrate that CCR plays a significant role in providing butyryl-CoA for monensin A biosynthesis and is present in wild-type S. cinnamonensis C730.1 at a level sufficient that the availability of the appropriate substrate (crotonyl-CoA) is limiting.

Acetates↗

Targeting human immunodeficiency virus (HIV) type 2 integrase protein into HIV type 1.

Integrase (IN) is the only retroviral enzyme necessary for the integration of retroviral cDNA into the host cell's chromosomes. The structure and function of IN is highly conserved. The human immunodeficiency virus type 2 (HIV-2) IN has been shown to efficiently support 3' processing and strand transfer of HIV-1 DNA substrate in vitro. To determine whether HIV-2 IN protein (IN(2)) could substitute for HIV-1 IN function in vivo, we used HIV-1 Vpr to deliver the IN(2) into IN mutant HIV-1 virions by expression in trans as a Vpr-IN fusion protein. Trans-complementation with IN(2) markedly increased the infectivity of IN-minus HIV-1. Compared with the homologous trans-IN protein, infectivity was increased to a level of 16%. Since IN has been found to play a role in reverse transcription (Wu et al., J. Virol. 73:2126-2135, 1999), cells infected with IN(2)-complemented HIV-1 were analyzed for DNA products of reverse transcription. DNA levels of approximately 18% of that of wild type were detected. The homologous trans-IN protein restored the synthesis of viral cDNA to approximately 86% of that of wild-type virus. By complementing integration-defective HIV-1 IN mutant viruses, which were not impaired in cDNA synthesis, the trans-IN(2) protein was shown to support integration up to a level of 55% compared with that of the homologous trans-IN protein. The delivery of heterologous IN protein into HIV-1 particles in trans offers a novel approach to understand IN protein function in vivo.

DNA, Complementary↗

Human immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex.

The human immunodeficiency virus type 1 (HIV-1) integrase protein (IN) is essential for integration of the viral DNA into host cell chromosomes. Since IN is expressed and assembled into virions as part of the 160-kDa Gag-Pol precursor polyprotein and catalyzes integration of the provirus in infected cells as a mature 32-kDa protein, mutations in IN are pleiotropic and may affect virus replication at different stages of the virus life cycle in addition to integration. Several different phenotypes have been observed for IN mutant viruses, including defects in virion morphology, protein composition, reverse transcription, nuclear import, and integration. Because the effects of mutations in the IN domain of Gag-Pol can not always be distinguished from those of mutations in the mature IN protein, there remains a significant gap in our understanding of IN function in vivo. To directly analyze the function of the mature IN protein itself, in the context of a replicating virus but independently from that of Gag-Pol, we used an approach developed in our laboratory for incorporating proteins into HIV virions by their expression in trans as fusion partners of either Vpr or Vpx. By providing IN in trans as a Vpr-IN fusion protein, our analysis revealed, for the first time, that the mature IN protein is essential for the efficient initiation of reverse transcription in infected cells and that this function does not require the IN protein to be enzymatically (integration) active. Our findings of a direct physical interaction between IN and reverse transcriptase and the failure of heterologous HIV-2 IN protein to efficiently support reverse transcription indicate that this novel function occurs through specific interactions with other viral components of the reverse transcription initiation complex. Studies involving complementation between integration- and DNA synthesis-defective IN mutants further support this conclusion and reveal that the highly conserved HHCC motif of IN is important for both activities. These findings provide important new insights into IN function and reverse transcription in the context of the nucleoprotein reverse transcription complex within the infected cell. Moreover, they validate a novel approach that obviates the need to mutate Gag-Pol in order to study the role of its individual mature components at the virus replication level.

DNA, Viral↗

A G1 cyclin is necessary for maintenance of filamentous growth in Candida albicans.

Candida albicans undergoes a dramatic morphological transition in response to various growth conditions. This ability to switch from a yeast form to a hyphal form is required for its pathogenicity. The intractability of Candida to traditional genetic approaches has hampered the study of the molecular mechanism governing this developmental switch. Our approach is to use the more genetically tractable yeast Saccharomyces cerevisiae to yield clues about the molecular control of filamentation for further studies in Candida. G1 cyclins Cln1 and Cln2 have been implicated in the control of morphogenesis in S. cerevisiae. We show that C. albicans CLN1 (CaCLN1) has the same cell cycle-specific expression pattern as CLN1 and CLN2 of S. cerevisiae. To investigate whether G1 cyclins are similarly involved in the regulation of cell morphogenesis during the yeast-to-hypha transition of C. albicans, we mutated CaCLN1. Cacln1/Cacln1 cells were found to be slower than wild-type cells in cell cycle progression. The Cacln1/Cacln1 mutants were also defective in hyphal colony formation on several solid media. Furthermore, while mutant strains developed germ tubes under several hypha-inducing conditions, they were unable to maintain the hyphal growth mode in a synthetic hypha-inducing liquid medium and were deficient in the expression of hypha-specific genes in this medium. Our results suggest that CaCln1 may coordinately regulate hyphal development with signal transduction pathways in response to various environmental cues.

Actins↗

Neutrophil elastase and elastase-rich cystic fibrosis sputum degranulate human eosinophils in vitro.

Neutrophils, eosinophils, and their proinflammatory constituents are important mediators of airway disease, and high levels of neutrophil proteases and eosinophil cationic protein (ECP) are found in sputum from patients with cystic fibrosis (CF). To investigate whether neutrophil proteases or CF sputum causes eosinophil degranulation, purified eosinophils from atopic asthmatic subjects were incubated for 2 h with neutrophil elastase, cathepsin G, and CF sputum, and the release of ECP was measured. We found that the percent release of ECP was higher after incubation with neutrophil elastase (10(-5) M) than with a buffer control [6.1 +/- 0.8 (SE) vs. 1.7 +/- 0.1%; P < 0.003] and represented >50% of the release caused by positive controls [Ca2+ ionophore A-23187 (5 x 10(-6) M) or serum-coated Sephadex beads]. The release of ECP after incubation with cathepsin G (2.3 +/- 0.2%) and CF sputum (6.2 +/- 2.0%) was also significantly higher than that with a buffer control (P < 0.05). Neutralization of free elastase activity with alpha1-proteinase inhibitor reduced the mean percent degranulation of eosinophils by neutrophil elastase by 50% (P = 0.0004) and by CF sputum by 75% (P = 0.02). Preincubation of eosinophils with cytochalasin B (10 mg/ml) and depletion of the incubation medium of Ca2+ also significantly attenuated degranulation of eosinophils incubated with purified free neutrophil elastase or CF sputum (P < 0.05). We conclude that neutrophil proteases, especially neutrophil elastase, and elastase-rich CF sputum cause degranulation of eosinophils in a mechanism partially dependent on Ca2+ and actin filaments.

Adult↗

No mutation of G209A in the alpha-synuclein gene in sporadic Parkinson's disease among Taiwan Chinese.

The role of genetics in Parkinson's disease (PD), previously controversial, is now supported by several studies. A major breakthrough has been the discovery of a single gene defect in familial Parkinson's disease. A single base pair change at position 209 from G to A (G209A) in the fourth exon of the alpha-synuclein gene has been identified in cases of familial PD. We looked for this mutation in 65 cases of sporadic PD in Taiwan Chinese patients but found none of these patients with this mutation. We conclude that mutation of G209A in the alpha-synuclein gene plays no role in sporadic PD among Taiwan Chinese.

Asian People↗

Ontogeny of self-sustaining status epilepticus.

Rat pups of ages of 20, 25, 30 and 35 postnatal days were subjected to the perforant-path stimulation model of status epilepticus (SE). This treatment resulted in age- and stimulus-frequency-dependent loss of inhibition in the dentate granule cell layer. Only 35% of the 20-day-old animals, but 88% of the 35-day-olds, progressed to self-sustaining status epilepticus (SSSE). Loss of inhibition as measured by 0.1-Hz paired-pulse testing and histologic damage that extended to the contralateral side, including both the hilus and some extrahippocampal limbic structures, were associated with SSSE. This model of SE differs from in vitro models of SE, in which immature animals show an increased susceptibility to epileptogenic stimuli, and provides us with a novel method to study epileptogenicity in the developing brain.

Animals↗