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Biomedical subjects

J Liang

Publications and source records attributed to J Liang.

At least 37 records · Page 2Linked to original sources
PubMed2004

Withholding and withdrawal of therapy in New Zealand intensive care units (ICUs): a survey of clinical directors.

Withdrawing and withholding life-support therapy in patients who are unlikely to survive despite treatment are common practices in intensive care units (ICUs). The literature suggests there is a large variation in practice between different ICUs in different parts of the world. We conducted a postal survey among all public ICUs in New Zealand to investigate the pattern of practice in withholding and withdrawal of therapy. Nineteen ICUs responded to this survey and they represented 74% of all the public ICU beds and 83% of the annual ICU admissions. The percentage of ICU admissions with therapy withdrawn or withheld was less than 10% in most ICUs. Only a small percentage (21%) of ICUs had a formal policy in withholding and withdrawal of therapy. The timing of making the decision to withhold or withdraw therapy was very variable. The patient and/or the family, the primary medical team consultant, two or more ICU consultants, and ICU nurses were usually involved in the decision making process. ICU nurses were more commonly involved in the decision making process in smaller ICUs (5 beds vs 10 beds, P = 0.03). The patient's pre-ICU quality of life, medical comorbidities, predicted mortality, predicted post-ICU quality of life, and the family's wishes were important factors in deciding whether ICU therapy would be withheld or withdrawn. Hospice ward or the patient's home was the preferred place for palliative care in 32% of the responses.

APACHE↗
PubMed2003

Physiological aspects of vetiver grass for rehabilitation in abandoned metalliferous mine wastes.

Physiological aspects of why vetiver grass (Vetiveria zizanioides L.) can be tolerant to heavy metals and be used as an alternative method for rehabilitation of abandoned metalliferous mine wastelands have been investigated. The results showed that high proportions of lead and zinc (Pb/Zn) tailing greatly inhibited the leaf growth, dry matter accumulation, and photosynthesis of leaves, but stimulated the accumulation of proline and abscisic acid (ABA), and enhanced the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), implying that different mechanisms to detoxify active oxygen species (AOS) existed in different parts of plants. Physiological responses to heavy metal treatments differed greatly between roots and shoots. Nitrogen fertilizer application could greatly alleviate the adverse effects of high proportions of Pb/Zn tailing on vetiver grass growth.

Abscisic Acid↗
PubMed2003

Invasion of Salmonella enteritidis in the tissues of reproductive organs in laying Japanese quail: an immunocytochemical study.

The aim of this study was to determine whether Salmonella enteritidis (SE) inoculated into the peritoneal cavity would colonize tissues of reproductive organs in Japanese quail hens. Quail hens regularly laying were intraperitoneally inoculated with 5 x 10(7) or 5 x 10(8) SE cells, and the ovary, oviduct, kidney, spleen, liver, and large intestine were excised 24 or 48 h after the treatment. Paraffin sections of these organs were immunostained for SE. Invasion of SE was found in the tissues of the ovarian stroma, the follicular wall including superficial and theca layers, and occasionally in the granulosa layer and yolk. The SE immunoreaction product frequently was found in the fibroblast-like and macrophage-like cells in the stroma and surface layer of follicles. The SE immunoreaction products were identified on the mucosal surface, in the mucosal epithelium, and in the stromal tissues in all segments of the oviduct. Many of the bacteria were contained in the cytoplasm of mucosal epithelial cells and stromal cells in those tissues. The SE immunoreactions were also found in the tissues of kidney, spleen, and liver and in the large intestine. These results suggest that SE organisms introduced into the peritoneal cavity can invade and colonize the tissues of ovary and oviduct and may be responsible in the production of contaminated eggs.

Animals↗
PubMed2003

Reducing uncertainties in volumetric image based deformable organ registration.

Applying volumetric image feedback in radiotherapy requires image based deformable organ registration. The foundation of this registration is the ability of tracking subvolume displacement in organs of interest. Subvolume displacement can be calculated by applying biomechanics model and the finite element method to human organs manifested on the multiple volumetric images. The calculation accuracy, however, is highly dependent on the determination of the corresponding organ boundary points. Lacking sufficient information for such determination, uncertainties are inevitable-thus diminishing the registration accuracy. In this paper, a method of consuming energy minimization was developed to reduce these uncertainties. Starting from an initial selection of organ boundary point correspondence on volumetric image sets, the subvolume displacement and stress distribution of the whole organ are calculated and the consumed energy due to the subvolume displacements is computed accordingly. The corresponding positions of the initially selected boundary points are then iteratively optimized to minimize the consuming energy under geometry and stress constraints. In this study, a rectal wall delineated from patient CT image was artificially deformed using a computer simulation and utilized to test the optimization. Subvolume displacements calculated based on the optimized boundary point correspondence were compared to the true displacements, and the calculation accuracy was thereby evaluated. Results demonstrate that a significant improvement on the accuracy of the deformable organ registration can be achieved by applying the consuming energy minimization in the organ deformation calculation.

Algorithms↗
PubMed2003

Adapting inverse planning to patient and organ geometrical variation: algorithm and implementation.

Image guided radiotherapy has the potential to improve both tumour control and normal tissue sparing by including temporal patient specific geometry information into the adaptive planning process. In this study we present a practical method of image guided adaptive inverse planning based on computed tomography (CT) and portal image feedback during the treatment course. The method is based on a general description of the radiotherapy optimization problem subject to dynamic geometrical variations of the patient/organs. We will demonstrate the feasibility of off-line image feedback into the inverse planning process with the example of three prostate cancer patients. CT and portal images acquired during the early course of the treatment are used to predict the geometrical variation distribution of a patient and to re-optimize the treatment plan accordingly. We will study the convergence of the optimization problem with respect to the number of image measurements and adaptive feedback loops.

Algorithms↗
PubMed2003

Withholding and withdrawal of therapy in patients with acute renal injury: a retrospective cohort study.

The incidence of withholding and withdrawal of therapy in the setting of multi-organ failure in critically ill patients has increased. Epidemiological data on the decision-making process of withholding or withdrawal of therapy from Australian and New Zealand intensive care units is sparse. We examined the clinical and electronic records of 179 consecutive patients, admitted to the ICU between 1st January 2000 and 31st December 2001, who had acute renal injury. Acute renal replacement therapy was offered in 11.2% of patients. Therapy was withheld or withdrawn in 21.2% of patients. The levels of supportive care were comparable between those who had therapy withheld or withdrawn and those who had full intensive care therapy until such a decision was made. Predicted mortality (OR 1.04, 95% CI: 1.01-1.08, P = 0.03) and age (OR 1.04, 95% CI: 1.00-1.08, P = 0.03) were independently associated with the decision to withhold or withdraw therapy. The mean ICU stay of those with withdrawal or withholding of therapy was much shorter than those with full therapy (2.5 vs 5.7 days). This was likely to be due to an older age of our cohort, rapid progressive nature of the acute disease, a different clinical approach to treating critically ill elderly patients, or a combination of these factors. This pattern of practice was quite different from those reported from ICUs in other parts of the world. A prospective multi-centre observational study will clarify the pattern of practice in this important area of intensive care practice in Australasia.

Acute Kidney Injury↗
PubMed2003

Clinical predictors of acute renal replacement therapy in critically ill patients with acute renal impairment.

OBJECTIVE: To investigate the early predictors of acute renal replacement therapy (RRT) in critically ill patients with acute renal impairment. METHODS: A retrospective study of the clinical and laboratory records of all critically ill adult patients with acute renal impairment admitted to a 6-bed multidisciplinary intensive care unit of a general teaching hospital between 1 January 2000 and 31 December 2001 were reviewed to determine risk factors for RRT. Acute renal impairment was defined as an acute increase in plasma creatinine of > 0.12 mmol/L and urea of > 8 mmol/L or an increase in plasma creatinine of > 0.06 mmol/L from the baseline level in patients who had chronic renal impairment. RESULTS: A cohort of 179 critically ill patients with acute renal impairment were identified. The mean APACHE II score was 23.4 and RRT was required in 11.2% of patients. The final logistic regression model showed that the requirement for noradrenaline (OR 29.0; 95% CI: 1.92 - 436.4, p = 0.015) was a positive risk factor and an increase in the average hourly urine output after intravenous frusemide (post-frusemide average hourly urine output/pre-frusemide average hourly urine output, OR 0.08; 95% CI: 0.02 - 0.32, p = 0.0004) was a negative risk factor for the requirement of RRT (area under the ROC curve = 0.88, 95% CI: 0.82 - 0.94, p = 0.001). CONCLUSIONS: After adequate fluid resuscitation, poor urinary output response to intravenous frusemide coupled with requirement for noradrenaline predicted the requirement for RRT in critically ill patients with early acute renal impairment in our intensive care unit.

Journal Article↗
PubMed2002

Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues.

Decorin (dcn) and biglycan (bgn), two members of the family of small leucine-rich proteoglycans (SLRPs), are the predominant proteoglycans expressed in skin and bone, respectively. Targeted disruption of the dcn gene results in skin laxity and fragility, whereas disruption of the bgn gene results in reduced skeletal growth and bone mass leading to generalized osteopenia, particularly in older animals. Here, we report that bgn deficiency leads to structural abnormality in collagen fibrils in bone, dermis, and tendon, and to a "subclinical" cutaneous phenotype with thinning of the dermis but without overt skin fragility. A comparative ultrastructural study of different tissues from bgn- and dcn-deficient mice revealed that bgn and dcn deficiency have similar effects on collagen fibril structure in the dermis but not in bone. Ultrastructural and phenotypic analysis of newly generated bgn/dcn double-knockout (KO) mice revealed that the effects of dcn and bgn deficiency are additive in the dermis and synergistic in bone. Severe skin fragility and marked osteopenia characterize the phenotype of double-KO animals in which progeroid changes are observed also in the skin. Ultrastructural analysis of bone collagen fibrils in bone of double-KO mice reveals a complete loss of the basic fibril geometry with the emergence of marked "serrated fibril" morphology. The phenotype of the double-KO animal mimics directly the rare progeroid variant of human Ehlers-Danlos syndrome (EDS), in which skin fragility, progeroid changes in the skin (reduced hypodermis), and osteopenia concur as a result of impaired glycosaminoglycan (GAG) linking to bgn and dcn core proteins. Our data show that changes in collagen fibril morphology reminiscent of those occurring in the varied spectrum of human EDS are induced by both bgn deficiency and den deficiency in mice. The effects of an individual SLRP deficiency are tissue specific, and the expression of a gross phenotype depends on multiple variables including level of expression of individual SLRPs in different tissues and synergisms between different SLRPs (and likely other macromolecules) in determining matrix structure and functional properties.

Animals↗
PubMed2001

Sustained unilateral blockade of rat striatal M(1) muscarinic receptors with m1-toxin1 in vivo.

m1-Toxin1 is a trace component of the venom of the green mamba that antagonizes M(1) muscarinic receptors specifically and irreversibly in vitro. It was injected into the right caudatoputamen of Wistar rats to occlude M(1) receptors specifically for several days ("M(1) knockdown"), and to begin to establish the unknown effects of striatal M(1)-neurotransmission on movement. The extent and duration of M(1)-blockade were evaluated with receptor binding assays and light microscopic autoradiography, using 1-2 nM [3H]pirenzepine to assess unoccupied M(1) receptors. An injection of 27 pmol m1-toxin1 blocked almost all of the M(1) receptors in one caudatoputamen (4 pmol), followed by their slow recovery to supranormal levels (115%) during a week. During maximum M(1)-blockade, the binding of 1 nM [3H]N-methylscopolamine to striatal membranes was reduced by only half, indicating no blockade of M(4) receptors, which comprise 51% of striatal muscarinic receptors. It is concluded that m1-toxin1 can produce acute, focal, selective, unilateral and long-lasting M(1)-blockade for investigations of the effects of M(1)-neurotransmission in vivo. Rats with extensive unilateral striatal M(1)-blockade appeared normal, and did not show unilateral deficits in spontaneous forearm use, in contrast to rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. Since M(1)-blockade should decrease the activity of both striatonigral and striatopallidal projection neurons, and the relative activity of these neurons is believed to control movement, the results suggest that a balanced decrease in the activity of these neurons on one side of the brain does not produce a right/left imbalance in spontaneous movement.

Acetylcholine↗
PubMed2001

Regulation of glycosaminoglycan function by osmotic potentials. Measurement of water transfer during antithrombin activation by heparin.

The sulfated glycosaminoglycan heparin is an important anticoagulant, widely used to treat and to prevent arterial thrombosis. Heparin triggers conformational changes in, and the functional activation of, the serine proteinase inhibitor antithrombin. We investigated water-transfer reactions during the activation process to explore the possibility that functional interaction between antithrombin and sulfated glycosaminoglycans can be regulated by osmotic potentials. Volume of water transferred upon heparin binding was measured from differences in free energy change, Delta(Delta G), with osmotic stress, pi. Osmotic stress was induced with chemically inert probes that are geometrically excluded from the water-permeable spaces of antithrombin and from intermolecular spaces formed during the association reaction. The free energy change, Delta G, for the antithrombin/heparin interaction was calculated from the dissociation constant, determined by functional titrations of heparin with antithrombin at fixed concentrations of the coagulation protease factor Xa. The effect of osmotic stress was independent of the chemical nature of osmotic probes but correlated with their radius up to radius >17 A. In mixtures including a large and a small probe, the effect of the large probe was not modified by the small probe added at a large molar excess. With an osmotic probe of 4-A radius, the Delta(Delta G)/pi slope corresponds to a transfer of 119 +/- 25 water molecules to bulk solution on formation of the complex. Analytical characterization of water-permeable volumes in x-ray-derived bound and free antithrombin structures revealed complex surfaces with smaller hydration volumes in the bound relative to the free conformation. The residue distribution in, and atomic composition of, the pockets containing atoms from residues implicated in heparin binding were distinct in the bound versus free conformer. The results demonstrate that the heparin/antithrombin interaction is linked to net water transfer and, therefore, can be regulated in biological gels by osmotic potentials.

Antithrombins↗
PubMed2001

Helix-helix packing and interfacial pairwise interactions of residues in membrane proteins.

Helix-helix packing plays a critical role in maintaining the tertiary structures of helical membrane proteins. By examining the overall distribution of voids and pockets in the transmembrane (TM) regions of helical membrane proteins, we found that bacteriorhodopsin and halorhodopsin are the most tightly packed, whereas mechanosensitive channel is the least tightly packed. Large residues F, W, and H have the highest propensity to be in a TM void or a pocket, whereas small residues such as S, G, A, and T are least likely to be found in a void or a pocket. The coordination number for non-bonded interactions for each of the residue types is found to correlate with the size of the residue. To assess specific interhelical interactions between residues, we have developed a new computational method to characterize nearest neighboring atoms that are in physical contact. Using an atom-based probabilistic model, we estimate the membrane helical interfacial pairwise (MHIP) propensity. We found that there are many residue pairs that have high propensity for interhelical interactions, but disulfide bonds are rarely found in the TM regions. The high propensity pairs include residue pairs between an aromatic residue and a basic residue (W-R, W-H, and Y-K). In addition, many residue pairs have high propensity to form interhelical polar-polar atomic contacts, for example, residue pairs between two ionizable residues, between one ionizable residue and one N or Q. Soluble proteins do not share this pattern of diverse polar-polar interhelical interaction. Exploratory analysis by clustering of the MHIP values suggests that residues similar in side-chain branchness, cyclic structures, and size tend to have correlated behavior in participating interhelical interactions. A chi-square test rejects the null hypothesis that membrane protein and soluble protein have the same distribution of interhelical pairwise propensity. This observation may help us to understand the folding mechanism of membrane proteins.

Bacterial Proteins↗
PubMed2001

Controlled release of clot-dissolving tissue-type plasminogen activator from a poly(L-glutamic acid) semi-interpenetrating polymer network hydrogel.

With the aim of developing an effective therapeutic modality for treatment of thrombosis, a tissue-type plasminogen activator (t-PA)-loaded porous poly(L-glutamic acid) (PLGA) semi-interpenetrating polymer network (semi-IPN) hydrogel was developed as a possible local drug delivery system. Porous structure of hydrogel was essential in this system to yield a large surface area so that t-PA release could be facilitated. This semi-IPN hydrogel was prepared using the method of free-radical polymerization and crosslinking of polyethylene glycol (PEG)-methacrylate through the PLGA network. Sodium bicarbonate (NaHCO(3)) was added to function as a foaming agent under acidic conditions, rendering the semi-IPN hydrogel to be porous. While the added NaHCO(3) provided gas foam in the reaction mixture, the pH in the hydrogel increased to about 7 to 8, which stimulated the polymerization. The porous structure that was presented at both the surface and sublayer was stabilized during hydrogel formation and freeze-drying. The hydrogel thus prepared possessed a porous structure of 10-20 microm in diameter, as determined by scanning electron microscopy. Results showed that the above hydrogel preparation process did not significantly alter the specific activity of the entrapped t-PA with regard to plasminogen activation and fibrin clot lysis ability. The t-PA release from this semi-IPN hydrogel was examined by measuring the plasmin activity using the chromogenic substrate S-2251. Findings in this paper demonstrated that the porous structure of the hydrogel facilitated t-PA release when compared to the dense structure. Aside from the porous structure, other factors including the content of the crosslinker, PLGA and t-PA could all be varied to regulate t-PA release from the hydrogel. These results suggest that a porous PLGA semi-IPN hydrogel could potentially be a useful local delivery system to release active t-PA primarily at the site of a thrombus.

Blood Coagulation↗
PubMed2001

Highly abundant genes in the transcriptosome of human and baboon CD34 antigen-positive bone marrow cells.

Nonhuman primates are useful large animal model systems for the in vivo study of hematopoietic stem cell biology. To better understand the degree of similarity of the hematopoietic systems between humans and baboons, and to explore the relevance of such studies in nonhuman primates to humans, this study was designed to compare the global gene expression profile of bone marrow CD34(+) cells isolated from these 2 species. Human complementary DNA (cDNA) filter arrays containing 25 920 human cDNAs were surveyed for this purpose. The expression pattern and relative gene abundance of the 2 RNA sources were similar, with a correlation coefficient of 0.87. A total of 15 970 of these cDNAs were expressed in human CD34(+) cells, of which the majority (96%) varied less than 3-fold in their relative level of expression between human and baboon. Reverse transcriptase-polymerase chain reaction analysis of selected genes confirmed that expression was comparable between the 2 species. No species-restricted transcripts have been identified, further reinforcing the high degree of similarity between the 2 populations. A subset of 1554 cDNAs, which are expressed at levels 100-fold and greater than background, is described, which includes 959 expressed sequence tags and uncharacterized cDNAs, and 595 named genes, including many that are clearly involved in hematopoiesis. The cDNAs reported here represent a selection of some of the most highly abundant genes in hematopoietic cells and provide a starting point to develop a profile of the transcriptosome of CD34(+) cells.

Animals↗
PubMed2001

Microsomal triglyceride transfer protein binding and lipid transfer activities are independent of each other, but both are required for secretion of apolipoprotein B lipoproteins from liver cells.

Recent studies indicate that microsomal triglyceride transfer protein (MTP) and apolipoprotein B (apoB) interact physically via two specific binding sites located within the amino-terminal globular region of apoB100. The first site is thought to be within the first 5.8% of the amino-terminal sequence, and the second site is between 9 and 16% of the amino-terminal sequence. It is not clear from prior studies whether these sites have unique or overlapping functions. Furthermore, there are no data differentiating between lipid transfer and potential chaperone functions of MTP. In the present study we have attempted to further characterize the physiologic interaction between apoB and MTP and to determine the relationship between the binding and lipid transfer aspects of the interaction. HepG2 cells were transiently transfected with apoB cDNAs, and MTP binding to apoB polypeptides was determined by two-step immunoprecipitation. MTP bound equally well to apoB polypeptides with (apoB13, 16,beta, apoB34, and apoB42) or without (apoB16, apoB13, and 16 or apoB13, 13, and 16) beta sheet domains. When proteasomal degradation of newly synthesized apoB polypeptides was blocked, MTP binding to all of the apoB polypeptides was only modestly affected by lipid availability and was independent of MTP-associated lipid transfer. Furthermore, MTP did not bind directly to a portion of the first beta sheet domain. We created two apoB constructs (apoB16del and apoB34del) by deleting the first 210 amino acids of apoB16 and apoB34. These apoB polypeptides, therefore, lacked the putative first MTP binding site. MTP binding to apoB16del and apoB34del was decreased significantly. However, the secretion of apoB16del was not different from apoB16, whereas the secretion of apoB34del was impaired significantly. Our results indicate that the interaction between MTP and apoB involves independent binding and lipid transfer activities but that both activities are required for the secretion of apolipoprotein B from liver cells.

Animals↗
PubMed2001

DNA sequencing by capillary electrophoresis using copolymers of acrylamide and N,N-dimethylacrylamide.

Copolymers of acrylamide (AM) and N,N-dimethylacrylamide (DMA) with AM to DMA molar ratios of 3:1, 2:1 and 1:1 and molecular weights of about 2.2 MDa were synthesized. The polymers were tested as separation media in DNA sequencing analysis by capillary electrophoresis (CE). The dynamic coating ability of polydimethylacrylamide (PDMA) and the hydrophilicity of polyacrylamide (PAM) have been successfully combined in these random copolymers. A separation efficiency of over 10 million theoretical plates per meter has been reached by using the bare capillaries without the additional polymer coating step. Under optimized separation conditions for longer read length DNA sequencing, the separation ability of the copolymers decreased with decreasing AM to DMA molar ratio from 3:1, 2:1 and 1:1. In comparison with PAM, the copolymer with a 3:1 AM:DMA ratio showed a higher separation efficiency. By using a 2.5% w/v copolymer with 3:1 AM:DMA ratio, one base resolution of 0.55 up to 699 bases and 0.30 up to 963 bases have been achieved in about 80 min at ambient temperatures.

Acrylamides↗
PubMed2001

Are proteins well-packed?

The average packing density inside proteins is as high as in crystalline solids. Does this mean proteins are well-packed? We go beyond average densities, and look at the full distribution functions of free volumes inside proteins. Using a new and rigorous Delaunay triangulation method for parsing space into empty and filled regions, we introduce formal definitions of interior and surface packing densities. Although proteins look like organic crystals by the criterion of average density, they look more like liquids and glasses by the criterion of their free volume distributions. The distributions are broad, and the scalings of volume-to-surface, volume-to-cluster-radius, and numbers of void versus volume show that the interiors of proteins are more like randomly packed spheres near their percolation threshold than like jigsaw puzzles. We find that larger proteins are packed more loosely than smaller proteins. And we find that the enthalpies of folding (per amino acid) are independent of the packing density of a protein, indicating that van der Waals interactions are not a dominant component of the folding forces.

Computer Simulation↗