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Biomedical subjects

D Liu

Publications and source records attributed to D Liu.

877 records · Page 49Linked to original sources

Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain.

How neuronal activity changes cerebral blood flow is of biological and practical importance. The rodent whisker-barrel system has special merits as a model for studies of changes in local cerebral blood flow (LCBF). Stimulus-evoked changes in neural firing and 'intrinsic signals' recorded through a cranial window were used to define regions of interest for repeated flow measurements. Whisker-activated changes in flow were measured with intravascular markers at the pia. LCBF changes were always prompt and localized over the appropriate barrel. Stimulus-related changes in parenchymal flow monitored continuously with H2 electrodes recorded short latency flow changes initiated in middle cortical layers. Activation that increased flow to particular barrels often led to reduced flow to adjacent cortex. Dye was injected into single penetrating arterioles from the pia of the fixed brain and injected into arterioles in slices of cortex where barrels were evident without stains. Arteriolar and venular domains at the surface were not directly related to underlying barrels. Capillary tufts in layer IV were mainly coincident with barrels. The matching between a capillary plexus (a vascular module) and a barrel (a functional neuronal unit) is a spatial organization of neurons and blood vessels that optimizes local interactions between the two. The paths of communication probably include: neurons to neurons, neurons to glia, neurons to vessels, glia to vessels, vessels to vessels and vessels to brain. Matching a functional grouping of neurons with a vascular module is an elegant means of reducing the risk of embarrassment for energy-expensive neuronal activity (ion pumping) while minimizing energy spent for delivery of the energy (cardiac output). For imaging studies this organization sets biological limits to spatial, temporal and magnitude resolution. Reduced flow to nearby inactive cortex enhances local differences.

Animals↗

Elevated plasma CD105 and vitreous VEGF levels in diabetic retinopathy.

Diabetic retinopathy is the leading cause of blindness in the industrialized world. Hyperglycaemia induces retinal hypoxia that upregulates a range of vasoactive factors which may lead to macular oedema and/or angiogenesis and hence potentially sight threatening retinopathy. In this study, we have focused on the association of CD105 and vascular endothelial growth factor (VEGF) with the development and progression of diabetic retinopathy by means of quantifying their expression in the plasma and vitreous of diabetic patients. CD105 levels were quantified in the plasma of 38 type I diabetic patients at various stages of retinopathy and 15 non-diabetic controls. In an additional cohort of 11 patients with advanced proliferative retinopathy and 23 control subjects, CD105 and VEGF were measured in the vitreous. The values were expressed as median (range) and statistical analysis was carried out using the non-parametric Mann-Whitney U test. Plasma CD105 levels were significantly increased in diabetic patients [1.8 (1.1-2.4) ng/ml] compared with non-diabetic controls [0.7 (0.3-1.8) ng/ml] (p<0.01). Plasma CD105 levels were elevated in diabetic patients with all stages of retinopathy, the highest level was observed in background retinopathy [2.3 (2.1-2.5) ng/ml] followed by proliferative retinopathy [2.1 (0.9-2.8) ng/ml] and advanced proliferative retinopathy [1.4 (0.6-1.8) ng/ml]. Vitreous contents of CD105 did not differ between controls and patients with advanced proliferative retinopathy, but vitreous levels of VEGF were elevated by approximately 3-fold in patients with advanced proliferative retinopathy [7.2 (1.90-15.60) ng/ml] compared with the control subjects [1.80 (1.10-2.210)] (p<0.01). These observations indicate that plasma levels of CD105 and vitreous levels of VEGF are associated with diabetic retinopathy, suggesting that CD105 and the angiogenic factor VEGF may play a critical role in the development and progression of diabetic retinopathy. Further studies are required to determine whether circulating CD105 levels could serve as a surrogate marker for early stage retinopathy and for monitoring disease progression.

Antigens, CD↗

Accumulation of rare earth elements in corn after agricultural application.

Using both pot and plot experiments, the dose-dependent accumulation of rare earth elements (REs) in corn (Zea mays L.) after application of an agricultural REs mixture was measured. In the pot experiment, the dose-dependent accumulation of REs in corn root and stem was observed, but it could not be detected in corn leaf under the dosage of 20 mg REs kg(-1) soil (oven-dry mass). The non-observed effect concentration (NOEC) for accumulation of REs in corn seedling with the pot experiment was 1.0 mg REs kg(-1). In the plot experiment, the dose-dependent accumulation was observed at an early stage after application of REs and the NOEC value of 32 mg REs m(-2) was obtained. At harvest, no dose-dependent accumulation of REs was observed in any part of the corn. These results can be confirmed by the fingerprinting analysis based on the differences between La to RE ratios in the REs mixture and in pot or plot soil. We observed that the plant shows no preference on individual RE and the results of fingerprinting indicated clearly the incorporation of exogenous REs in plant tissues, in a similar manner as that observed in the dose-dependent distribution of RE concentrations. The results indicated also a translocation process of REs from plant root to leaf when applied to soil or from leaf to root when applied to leaf. A homeostatic regulation mechanism for excessive uptake of REs in plants is suggested to regulate the concentrations of REs in the plant.

Agriculture↗

Intravenous bolus topotecan in patients with myelodysplastic syndrome.

We treated 16 patients with myelodysplastic syndromes with 24 courses of bolus topotecan. Patients received topotecan as a daily 15 minute infusion for 5 days at 3 dose levels (4.0 mg/m2/d, 2.0 mg/m2/d or 2.5 mg/m2/d). There was one complete response and one partial response (overall response rate 12%). Toxicity included myelosuppression, diarrhea, ileus and mucositis. There were 3 treatment-related deaths. The results of this schedule of topotecan appeared to be inferior to that reported with infusional topotecan in patients with MDS.

Adult↗

LEA.135 expression: its comparison with other prognostic biomarkers for patients with primary breast carcinoma.

The purpose of this retrospective study was to examine the prognostic value of expression of luminal epithelial antigen (LEA.135) for recurrence and overall survival of patients with primary invasive breast carcinoma by both univariate and multivariate analyses. The possible prognostic value of LEA.135 was also compared with some widely utilized prognostic biomarkers such as c-erbB 2, topoisomerase II.alpha (TPII.alpha), MIB 1, estrogen receptor (ER) and progesterone receptor (PR), as well as age of the patients and clinicopathologic parameters. The study was carried out by immunohistochemical methods on formalin-fixed/paraffin-embedded tissue sections in a series of 225 patients with median follow-up of 8.5 years. Prognostic significance of the biomarkers was determined by two-sided p value. In this series of patients, among the age and clinicopathologic parameters, only age, was significantly associated with a decreased overall survival (logrank p = 0.027). Among the prognostic biomarkers, TPII a expression at high (> 50% positive cells) or moderate (6-50% positive cells) level was associated with an increased rate of recurrence (logrank p < 0.001). However, the association of TPII.alpha expression with a decreased overall survival failed to reach a statistically significance. Expression of c-erbB 2 showed a trend of being associated with an increased probability of recurrence, but the association did not reach statistical significance. The remaining biomarkers were not associated with either the probability of recurrence or overall survival. LEA.135 expression was observed in 163 (72.4%) of the 225 patients. The patients with high (> 50% positive cells) or moderate (6-50% positive cells) level of LEA.135-positive cancer cells showed a significantly decreased probability of recurrence (logrank p < 0.001) and an increased overall survival (logrank p < 0.001) compared with those with LEA.135-negative cancer cells. The association remained significant by multivariate analysis for recurrence (likelihood ratio test p < 0.001) and overall survival (likelihood ratio test p < 0.001) when assessed with other prognostic parameters. Furthermore, the combination of LEA.135 with other prognostic biomarkers stratified four subgroups of patients with distinct clinical outcome. The subgroup of patients who were LEA.135+/TPII.alpha- showed the lowest probability of recurrence and the longest overall survival compared with those who were LEA.135-/TPII.alpha+ (logrank p < 0.001). Interestingly, the patients whose cancer cells were LEA.135+/TPII.alpha+, LEA.135+ MIB.1+ or LEA.135+/c-erbB 2+ experienced a decreased probability of recurrence and an increased overall survival compared with those with LEA.135-/TPII.alpha+, LEA.135- MIB.1+ or LEA.135-/c-erbB 2+ (logrank p < 0.001). The results demonstrated that LEA.135 is an independent and favorable prognostic biomarker for patients with primary invasive breast carcinoma, that the loss of LEA.135 expression is associated with aggressive phenotype of cancer cells during the breast cancer progression, and that its continued expression seems to override the adverse effects of expression of an oncogene or cell proliferation-associated molecules.

Age Factors↗

Nucleocapsid protemn gene of Chinese isolate of Bombyx mori nucleopolyhedrovirus.

The nucleocapsid protein gene (vp39) of a Chinese isolate of Bombyx mori nucleopolyhedrovirus (BmNPV-Ch), namely an open reading frame (ORF) of 1050 bp that codes for a polypeptide of 39 K (VP39) consisting of 350 amino acids was sequenced. The homology of the nucleotide (nt) and amino acid sequences of vp39 and VP39, respectively, of BmNPV-Ch and a Japanese isolate of BmNPV (BmNPV-Ja) were found to be 97.5% and 97.1%, respectively. The BmNPV-Ch vp39 is nine nucleotides longer than that of BmNPV-Ja vp39 due to insertion of CGA at nt 625 and GTCGGC at nt 985 910. There are differences in 17 nucleotides causing a few substitutions of amino acids which slightly modify the secondary structure of BmNPV-Ch. It indicates that the main part of the secondary structure of VP39 is a folded structure containing high proportion of beta-sheet and beta-turn units. A dot blot hybridization analysis revealed the existence of a homologous transcript of BmNPV-Ch vp39 in Sf9 cells infected with Autographa californica multiple nucleocapsid nucleopolyhedrovirus (AcMNPV).

Amino Acid Sequence↗

[Isolation by suppression-subtractive hybridization of genes preferentially expressed during early and late fiber development stages in cotton].

As a main natural fiber source, cotton plays an important role in human life. To identify genes preferentially expressed during early and late cotton fiber development, we constructed two fiber subtracted libraries on the basis of PCR-selected subtraction using a pool of nonfiber tissues as the same driver and 10 days postanthesis (DPA) and 20 DPA fiber cells as testers, respectively. Through differential screening, 292 clones in both libraries were identified as being preferentially expressed during fiber development. Sequence analysis showed that 31 unique sequences were found in the library of 10 DPA fibers and 48 unique sequences were obtained in the library of 20 DPA fibers. In addition, there were 13 unique clones in common in both libraries. Many previously reported cotton fiber-related genes were included in both libraries. Northern hybridization was performed to further confirm the differential expression and to determine the pattern of mRNA accumulation of selected clones. As a result, all selected cDNAs showed highly preferential expression in developing cotton fibers. Four genes-putative gibberellin-regulated protein, putative tonoplast intrinsic protein, putative plasma membrane intrinsic protein, and Gossypium hirsutum putative membrane protein-were identified in 10 DPA fiber subtracted library, and they were found to be expressed a lot during early fiber development. On the other hand, those genes screened out of 20 DPA fiber subtracted library, like arabinogalactan protein and fiber glycosyl hydrolase family 19 protein, were found highly expressed in fibers with the maximal transcription level during developmental switch from elongation to cellulose deposition. By subtraction between fibers and five nonfiber tissues, two sets of genes were identified, and their fiber-specific or fiber-preferential expression indicated that they are involved in the network that controls cotton fiber development.

Cloning, Molecular↗

Variation of insulin absorption during subcutaneous and peritoneal infusion in insulin-dependent diabetic patients with unsatisfactory long-term glycaemic response to continuous subcutaneous insulin infusion.

The aim of present study was to analyse the reproducibility of plasma-free insulin profiles of subcutaneously (CSII) and intraperitoneally (CIPII) administered insulin in 6 C-peptide-negative, type 1, diabetic patients. The patients were selected for CIPII because of unsatisfactory, long-term, metabolic response to CSII. Plasma-free insulin was measured repeatedly, twice during subcutaneous infusion and twice during intraperitoneal infusion, for 4 hours, following a standard breakfast. In the CSII experiment, insulin was given as a meal-dose of 0.1 U per kg body weight, and in the CIPII experiment the meal-dose was 0.05 U per kg body weight. The dose-induced peak occurred earlier after the CIPII than with the CSII (60.0 +/- 8.0 vs 133.6 +/- 16.3 min). In conclusion, the intra-patient coefficient of variation (C.V.) of plasma-free-insulin profiles at 0-60 min and 0.240 min, as well as the peak time, were markedly lower for CIPII insulin than for CSII, indicating a more reproducible way of insulin administration with CIPII in this selected group of patients.

Absorption↗

A novel electrochemical heparin sensor.

Heparin is one of the most important clinical drugs, and is employed universally during surgical procedures and extra-corporeal therapies to prevent blood from clotting. Its clinical use, however, is often associated with serious hemorrhagic complications. Because of this life threatening bleeding risk, there is a need for a simple sensing device that can rapidly and directly monitor heparin levels during extra-corporeal therapies to provide a safeguard during these procedures. Current heparin assays are all based on the measurement of blood clotting time, and none of them are suitable for direct and rapid determination of heparin. We describe applying conventional ion selective electrode (ISE) polymer membrane technology and using a specifically formulated membrane doped with tridodecylmethylammonium chloride (TDMAC) as the heparin complexing agent, to devise the first electrochemical sensor for heparin measurement. The sensor is capable of detecting directly and rather selectively the free heparin concentrations in both physiologic saline and undiluted plasma samples. In addition, the clinical utility of the sensor has been demonstrated by monitoring the levels of heparin in undiluted whole blood specimens obtained from patients undergoing open heart operations. It is envisioned that the sensor could be configured as an in-line device within extracorporeal blood loops to monitor current extracorporeal therapy, or as a convenient single use disposable device for rapid bedside or laboratory measurements of heparin in small discrete samples of undiluted whole blood. Preliminary studies concerning the feasibility of designing a mass fabricated, solid state, disposable heparin sensor also have been conducted.

Blood Chemical Analysis↗

Antibody mediated lung targeting of long-circulating emulsions.

Monoclonal antibody 34A, which specifically binds to a surface glycoprotein (thrombomodulin) of the pulmonary endothelial cell surface in mice, has been conjugated to the surface of long-circulating emulsions composed of Castor oil, phosphatidylcholine and polyethylene glycol coupled to distearoylphosphatidyl-ethanolamine. These antibody-containing emulsions were found capable of binding to the lung when injected into mice through the tail vein. The level of lung accumulation of these emulsions depends on the amount of antibodies conjugated to the surface of the emulsions. With an input antibody to lipid ratio of 2:1 (w/w), 30% injected emulsions were found in the lung 30 minutes after administration. Such high level accumulation can be blocked by co-administration of free 34A antibody, indicating that the binding is specific and 34A antibody mediated. Kinetic studies showed that emulsion targeting to the lung was very rapid. Five minutes after tail vein injection, the total amount of emulsion found in the lung was the highest among the time points examined, indicating the completion of lung binding. However, about 50% of the initially bound emulsions remained bound for more than 4 hours. These results indicate that the targeted drug delivery using oil-in-water emulsions could be very useful to enhance the therapeutic efficacy of lipophilic drugs.

Animals↗

Archival, formalin-fixed tissue: its use in the study of Alzheimer's type changes.

Preparing for a retrospective study of senile degeneration in schizophrenia, we had occasion to explore the suitability of an old collection formalin-fixed brains and paraffin blocks for study by modern staining methods. Tissue that had been in formalin for 50 years was embedded in paraffin. Sections were then stained with thioflavine S and with immunoperoxidase stains using Alz 50 and antibodies to paired helical filaments, ubiquitin, and beta-amyloid. In all 4 cases that had originally (50 years earlier) received neuropathologic diagnoses of Alzheimer's disease, large numbers of neocortical senile plaques and neurofibrillary tangles were clearly demonstrated by thioflavine S stain and by immunohistochemistry for paired helical filaments, ubiquitin, and beta-amyloid. In each of 4 other cases, in which the original neuropathologic examination had not revealed Alzheimer's disease, no plaques or tangles were observed. Immunoreactivity with Alz 50 was completely absent after 50 years in formalin. Examination of additional cases of Alzheimer's disease revealed that Alz 50 immunoreactivity was well preserved after 10 years in formalin and completely absent after 30 years in formalin. Alzheimer's disease tissue stored in paraffin for 30 years was clearly stained by all modalities. We conclude that immunohistochemical identification of senile plaques and neurofibrillary tangles is practical even after decades of storage in formalin or paraffin. The applicability of techniques that did not exist when these specimens were collected indicates that the systematic, permanent retention of formalin-fixed material may yield unanticipated future benefits.

Adult↗