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Biomedical subjects

Y Lu

Publications and source records attributed to Y Lu.

At least 1,009 records · Page 56Linked to original sources

AIT-082 and methylprednisolone singly, but not in combination, enhance functional and histological improvement after acute spinal cord injury in rats.

Extracellular non-adenine based purines are neuroprotective. Preliminary studies indicate that administration of the synthetic purine 4-[[3-(1,6 dihydro-6-oxo-9-purine-9-yl)-1-oxypropyl] amino] benzoic acid (AIT-082, leteprinim potassium) to rats immediately after acute spinal cord injury (SCI), improves functional outcome. The effects of potential new agents are often compared to methylprednisolone (MPSS). We evaluated the effects of AIT-082 and MPSS, separately and in combination, on the functional and morphological outcome of acute SCI in adult rats. After standardized T11-12 spinal cord compression rats were given intraperitoneally one of the following: vehicle (saline); MPSS (30 mg/kg or 60 mg/kg body weight, first dose 15 min after crush); AIT-082 (60 mg/kg body weight daily, first dose 15 min after crush); or AIT-082 plus MPSS. After 1, 3, or 21 days, the rats were perfused for histological analysis. AIT-082 administrations significantly reduced locomotor impairment from 121 days post-operatively. At 1 and 3 days post injury, AIT-082-treatment reduced tissue swelling, tissue loss and astrogliosis at the injured cords but did not alter the extent of hemorrhage and the number of macrophages and/or microglia. MPSS reduced hemorrhage and the number of macrophages and/or microglia, but did not alter astrogliosis. At 21 days, either AIT-082 or MPSS administration improved function and morphology similarly (less tissue loss and astrogliosis). In contrast, administration of AIT-082 and MPSS together abolished the beneficial effects observed when either drug was given individually. These results suggest that MPSS and AIT-082 may exert their beneficial effects through different and potentially antagonistic pathways.

Aminobenzoates↗

Purification of adrenal chromaffin cells increases antinociceptive efficacy of xenotransplants without immunosuppression.

We have found that immunosuppression is necessary for the survival of xenogeneic adrenal medullary transplants. Because chromaffin cells are essentially nonimmunogenic, it is likely that the highly immunogenic "passenger" cells in the transplant preparation bring about rejection. This article describes a procedure that produces an essentially pure preparation of chromaffin cells for transplantation. Bovine adrenal medullary cells were isolated and differentially plated, resulting in a semipurified preparation of chromaffin cells. Ferromagnetic beads were added to the cell suspension, some of which were phagocytized by endothelial cells, which allowed their removal by exposure to a magnet. The remaining cells were then exposed to ferromagnetic beads coated with isolectin B4 from Griffonia simplicifolia and once again to a magnetic field. The "semipurified" preparation contained approximately 90% chromaffin cells, whereas the "highly purified" preparation was > 99.5% chromaffin cells as determined immunohistochemically. The immunogenicity of the two cell preparations was assessed in vitro by determining their capacity to evoke lymphocyte proliferation. Rat spleen lymphocytes were mixed with either a highly purified or semipurified population of bovine chromaffin cells. The results of this assay demonstrated that the highly purified preparation was a much weaker stimulant of lymphocyte proliferation than was the semipurified preparation and may demonstrate better graft survival in vivo. Transplantation via intrathecal catheter of either 80,000 or 250,000 cells from the highly or partially purified preparations onto the lumbar spinal cord of nonimmunosuppressed and non-nicotine-stimulated rats produced a cell number-dependent antinociception for both A(delta) and C fiber-mediated thermonociception at 6 days after transplantation. After 6 days and up to 28 days, only the "highly purified" preparation showed antinociception. These results suggest that nearly complete purification of bovine chromaffin cells minimizes immunorejection of xenogeneic transplants of these cells.

Adrenal Medulla↗

Molecular basis of Fas and cytochrome c pathways of apoptosis induced by tartary buckwheat flavonoid in HL-60 cells.

In a previous study, we showed that tartary buckwheat flavonoid (TBF) induced HL-60 leukemic cell apoptosis, most likely via a caspase 3 activating pathway. The aim of this study was to further investigate the molecular mechanisms involved in TBF-induced apoptosis of HL-60 cells. Thus, death receptor Fas expression on HL-60 cells was detected by flow cytometry (FCM). We also studied the effect of TBF on intranuclear DNA binding activity of NF-kappaB, as well as release of mitochondrial cytochrome c into the cytosol in HL-60 cells by FCM. The results suggest that TBF-induced apoptosis of HL-60 cells may be stimulated by the release of cytochrome c to the cytosol, upregulation of Fas expression on the cell surface, and through a caspase-3-dependent mechanism. Furthermore, TBF-induced apoptosis may be partly regulated through the inactivation of NF-kappaB in HL-60 cells. The induction of apoptosis by TBF may be attributed to its cancer chemopreventive activity.

Apoptosis↗

Dielectric properties of human glioma and surrounding tissue.

Dielectric properties of human glioma and surrounding tissue from five patients were measured. Experiments were performed at frequencies of 5-500 MHz at 24 +/- 0.5 degrees C using a Network Analyser and a coaxial line capacitive sensor. The permittivity and conductivity of tumours were 30% higher than that of the surrounding tissues due to their higher water content. The characteristic of less differentiation in tumours clearly was reflected in the dielectric properties, namely a smaller parameter for the relaxation time distribution of the tumour's dielectric relaxation. With the dielectric data, the power absorption ratios of tumour to surrounding tissue were calculated for four representative electromagnetic (EM) irradiation cases. The calculation shows that power absorption ratios are strongly dependent on the incident direction of the EM wave and optimum frequency. To improve therapeutic efficiency, it is appropriate to have the electric field vector (E) parallel to the interface of tumour/surrounding tissue at optimum frequencies around 100 MHz, and the case of E perpendicular to the interface must be avoided in applications of EM hyperthermia for brain tumours.

Adult↗

A cross-cultural assessment of perceived health problems in the elderly.

To study cross-cultural differences in perceived health problems in the elderly the Nottingham Health Profile (NHP) developed by Hunt et al. was administered to subjects from the People's Republic of China and Australia. The Australian stratum was further categorized according to cardiovascular status. Analyses of covariance (with age as the covariate) on each of the six subscales of the NHP yielded significant differences for 'Energy', 'Pain', 'Emotional reactions', 'Social isolation' and 'Physical mobility'. No differences were found for the 'Sleep' subscale. Through comparisons between the mean scores for the four strata and from normative data it is concluded that it is likely that the NHP is 'culture free' on the dimensions 'Energy', 'Pain', 'Emotional reactions', 'Social isolation' and 'Physical mobility'.

Aged↗

Community-based rehabilitation: does it change community attitudes towards people with disability?

To achieve the goal of 'Health for All by the Year 2000' the World Health Organization (WHO) adopted an approach to rehabilitation described as community-based rehabilitation (CBR). A major objective of CBR is to develop positive community attitudes towards people with disabilities. To determine whether this objective can be achieved, post hoc measurement of attitudes towards people with disabilities was carried out in a community in which CBR had been established and in a control community. It is shown that both groups exhibited neutral attitudes. The community exposed to CBR obtained a mean attitude score significantly (p < 0.001) closer to the positive end of the scale than did the control community. It is concluded that communities in which CBR is being carried out develop more favourable attitudes towards people with disabilities than do those in which no such programme has been implemented.

Adult↗

Three multizone photorefractive keratectomy algorithms for myopia. The Melbourne Excimer Laser Group.

OBJECTIVE: To compare the efficacy and complications of three different excimer laser algorithms for multizone photorefractive and photoastigmatic keratectomy. METHODS: Three different software algorithms were applied to treat myopia and myopic astigmatism with the VISX 20/20 excimer laser. Each algorithm had a maximum ablation zone of 6 mm but differed in the number of zones employed, the proportion of the total treatment allocated to each ablation zone, and the treatment of astigmatism. The Melbourne multizone technique equally divided myopia correction into a maximum of three ablation zones. The Pop multizone technique biased myopia treatment into the smaller diameter zones to a maximum of six ablation zones, with one central island pretreatment. The Alpins multizone technique equally divided myopia treatment through all zones up to a maximum of six, with one central island pretreatment. RESULTS: A total of 585 patients (780 eyes) were treated and 625 eyes (80%) were followed for more than 6 months. The mean baseline spherical equivalent refractive error was -5.63 D (-1.00 to -19.50 D). Between 71 and 79% of eyes were treated for astigmatism. There was no statistically significant differences in baseline refractive error or other characteristics among the three groups. At 6 months, the Alpins multizone algorithm had more eyes with a refractive error within +/- 1.00 D of emmetropia (p = 0.01) and more within +/- 2.00 D of emmetropia (p < 0.01). This new algorithm produced more eyes with an uncorrected visual acuity of 20/20 or better at 6 months (p < 0.01). When multiple logistic regression was used to correct for any differences in baseline myopia among the three groups, this algorithm also had a higher odds ratio for achieving 20/20 or better uncorrected visual acuity (OR = 1.58). CONCLUSION: At 6 months, all three algorithms were effective in the reduction of myopia. Significantly better visual acuity and refractive results were achieved with the Alpins multizone algorithm that spread the total treatment over a larger number of ablation zones, with an equal number of diopters of treatment in each zone.

Adolescent↗

Selective abolition of the NMDA component of long-term potentiation in mice lacking mGluR5.

The mechanisms underlying the differential expression of long-term potentiation (LTP) by AMPA and NMDA receptors, are unknown, but could involve G-protein-linked metabotropic glutamate receptors. To investigate this hypothesis we created mutant mice that expressed no metabotropic glutamate receptor 5 (mGluR5), but showed normal development. In an earlier study of these mice we analyzed field-excitatory postsynaptic potential (fEPSPs) in CA1 region of the hippocampus and found a small decrease; possibly arising from changes in the NMDAR-mediated component of synaptic transmission. In the present study we used whole-cell patch clamp recordings of evoked excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons to identify the AMPAR- and NMDAR-mediated components of LTP. Recordings from control mice following tetanus, or agonist application (IS, 3R-1-amino-cyclopentane 1,3-dicarboxylic acid) (ACPD), revealed equal enhancement of the AMPA and NMDA receptor-mediated components. In contrast, CA1 neurons from mGluR5-deficient mice showed a complete loss of the NMDA-receptor-mediated component of LTP (LTP(NMDA)), but normal LTP of the AMPA-receptor-mediated component (LTP(AMPA)). This selective loss of LTP(NMDA) was seen in three different genotypic backgrounds and was apparent at all holding potentials (-70 mV to +20 mV). Furthermore, the LTP(NMDA) deficit in mGluR5 mutant mice could be rescued by stimulating protein kinase C (PKC) with 4beta-phorbol-12,13-dibutyrate (PDBu). These results suggest that PKC may couple the postsynaptic mGluR5 to the NMDA-receptor potentiation during LTP, and that this signaling mechanism is distinct from LTP(AMPA). Differential enhancement of AMPAR and NMDA receptors by mGluR5 also supports a postsynaptic locus for LTP.

Animals↗

Involvement of p21Waf1 in mediating inhibition of paclitaxel-induced apoptosis by epidermal growth factor in MDA-MB-468 human breast cancer cells.

Paclitaxel (Taxol) is currently one of the most widely used anti-cancer drugs for human breast cancer. In this study, we investigated how epidermal growth factor (EGF) modulated paclitaxel-induced apoptosis in MDA-MB-468 human breast adenocarcinoma cells. Pulse-exposure of the cells to paclitaxel resulted in cell death through apoptosis. When EGF was present during the post-paclitaxel culture period, this paclitaxel-induced apoptosis was inhibited in an EGF dose-dependent manner. The induction of apoptosis by paclitaxel was accompanied by an elevated level of p34cdc2 kinase activity, which was inhibited in the presence of EGF during the post-paclitaxel culture period. Exposure of MDA-MB-468 cells to EGF induced expression of the cyclin-dependent kinase inhibitor p21Waf1. Incubation of paclitaxel-treated MDA-MB-468 cell extracts with EGF-treated MDA-MB-468 cell extract, which exhibited elevation of p34cdc2 activity, inhibited the kinase activity. This inhibition was not observed with p21Waf1-immunodepleted EGF-treated cell extract. Transfection of the cells with p21Waf1 antisense oligonucleotide abolished the induction of p21Waf1 and also significantly reduced inhibition by EGF of paclitaxel-induced apoptosis. These studies demonstrate that p21Waf1 plays a key role in the inhibition of paclitaxel-induced apoptosis by EGF in MDA-MB-468 cells.

Adenocarcinoma↗

Thermal chondroplasty with radiofrequency energy. An in vitro comparison of bipolar and monopolar radiofrequency devices.

The purpose of this study was to examine the in vitro effects of three radiofrequency energy devices (two bipolar devices and one monopolar device) for the performance of thermal chondroplasty. Thirty-two fresh bovine femoral osteochondral sections (approximately 3 x 4 x 5 cm) from eight cows were divided into four groups (three treatment patterns and one sham-operated group with eight specimens per group). The three treatment patterns consisted of 1) radiofrequency energy delivered by a mechanical jig at 1 mm/sec in a contact mode (50 g of pressure), 2) radiofrequency energy delivered by a mechanical jig at 1 mm/sec in a noncontact mode (1 mm between probe tip and articular cartilage surface), and 3) radiofrequency energy smoothing of abraded cartilage during arthroscopic visualization. Thermal smoothing of the abraded cartilage surface was accomplished with all three devices. Significant chondrocyte death, as determined by confocal laser microscopy and cell viability staining, was observed with each device. The bipolar radiofrequency systems penetrated 78% to 92% deeper than the monopolar system. The bipolar systems penetrated to the level of the subchondral bone in all osteochondral sections during arthroscopically guided paintbrush pattern treatment. Radiofrequency energy should not be used for thermal chondroplasty until further work can establish consistent methods for limiting the depth of chondrocyte death while still achieving a smooth articular for thermal chondroplasty until further work can establish consistent methods for limiting the depth of chondrocyte death while still achieving a smooth articular surface.

Animals↗

Automated severity classification of AIDS hospitalizations.

To validate an automated AIDS severity-of-illness prognostic algorithm, 2,113 discharge summaries of HIV-infected patients were merged with the Problem-Oriented Medical Synopsis (POMS) and an HIV risk registry. The combination of a medically derived classification and staging algorithm with multivariate statistical techniques was used for automated severity-of-illness disease staging and prognostic assignment. The model correctly predicted the outcomes of 82% of all cases (death, survivorship) at discharge, and 66% of deaths.

Algorithms↗

Evaluation of N-4-(hydroxycarbophenyl) retinamide as a cancer prevention agent and as a cancer chemotherapeutic agent.

In this review, a retinoid analogue (N-4-hydroxycarbophenyl) retinamide (R11) has been evaluated for its pharmacological and clinical properties. R11 has been studied both as a cancer prevention agent, as well as, a cancer chemotherapeutic agent. R11 alone and in combination with other agents can be used for the treatment of cervical dysplasia or leukemia. This review will examine novel strategies and mechanisms of action for retinoids in the treatment and prevention of cancer.

Animals↗

Tumor necrosis factor and interleukin-1 stimulate testosterone secretion in adult male rat Leydig cells in vitro.

The actions of two cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), on testosterone production by dispersed adult testis cells and purified Leydig cells in culture were studied. In one set of experiments, testis cells from adult (90-day-old) rats were enzymatically dispersed. In another set of experiments, the dispersed testis cells were placed on a Percoll density gradient and were centrifuged to yield purified (greater than 85%) Leydig cells. Both whole testis cells and purified Leydig cells were cultured in the presence of varying doses of TNF or IL-1 with or without maximally stimulating doses of human chorionic gonadotropin (hCG). Both TNF and IL-1 stimulated basal secretion of testosterone in whole testis cells, as well as purified Leydig cells. Additionally, both TNF and IL-1 augmented maximally hCG stimulated testosterone secretion. Both cytokines stimulated testosterone secretion by dispersed testis cells as early as 4 hours, and the effect continued for up to 72 hours. The cytokines slightly, but significantly, stimulated testosterone production in purified Leydig cells after 24 hours, and continued for up to 72 hours. We have concluded from this data that TNF and IL-1 stimulate the testosterone secretion by adult rat Leydig cells. While this effect might be mediated through the action of the cytokines on testicular macrophages, there might also be a direct effect on the Leydig cell since augmentation of secretion occurred in purified Leydig cells, as well as whole testis cells. Therefore, TNF and IL-1 may serve as local regulators of Leydig cell function.

Animals↗

Inadequate dietary intake and altered nutrition status in early HIV-1 infection.

Recent studies indicate that multiple nutritional abnormalities occur relatively early in the course of human immunodeficiency virus (HIV-1) infection. Decreased plasma levels of vitamins B6, B12, A, and E and zinc have been correlated with dietary intake and associated with significant alterations in immune response and cognitive function. To determine the level of intake consistent with normal plasma nutrient levels, we examined nutrition status in relation to food consumption and nutrient supplementation in HIV-1-seropositive (HIV+) and -seronegative (HIV-) homosexual men. The mean level of total intake (diet plus supplements) for all nutrients was significantly higher in HIV+ men. To achieve normal plasma nutrient values, the HIV+ men appeared to require intake in multiples of the recommended dietary allowance (RDA) for vitamins A, E, B6, and B12 and zinc. For the HIV+ men, a relatively high proportion of biochemical deficiency was associated with consumption of vitamin B6 and zinc at the RDA level. Because little evidence of deficiency was observed with elevated intake in both groups, an effective program of nutritional supplementation may be beneficial in maintaining adequate plasma nutrient levels.

Adult↗

Lead suppresses chimeric human transferrin gene expression in transgenic mouse liver.

The major iron-transport protein in serum is transferrin (TF) which also has the capacity to transport other metals. This report presents evidence that synthesis of human TF can be regulated by the metal lead. Transgenic mice carrying chimeric human TF-chloramphenicol acetyl transferase (CAT) genes received lead or sodium salts by intraperitoneal injections or in drinking water. Transgene expression in liver was suppressed 31 to 50% by the lead treatment. Lead regulates human TF transgenes at the mRNA level since liver CAT enzyme activity, CAT protein, and TF-CAT mRNA levels were all suppressed. The dosages of lead did not alter synthesis of the other liver proteins, mouse TF and albumin, as measured by Northern blot analysis of total liver RNA and rocket immunoelectrophoresis of mouse sera. Moderate levels of lead exposure were sufficient to evoke the human TF transgene response; blood lead levels in mice that received lead acetate in drinking water ranged from 30 micrograms/dl to 56 micrograms/dl. In addition to suppressing expression of TF-CAT genes in transgenic mice, lead also suppressed synthesis of TF protein in cultured human hepatoma HepG2 cells. The regulation of human TF apparently differs from the regulation of mouse TF which is unresponsive to lead exposure.

Albumins↗

Chromium (IV)-mediated fenton-like reaction causes DNA damage: implication to genotoxicity of chromate.

This paper describes our deoxyribonucleic acid (DNA) damage and Fenton activity studies on Cr(IV) that were undertaken to examine a role of Cr(IV) in the biochemical mechanism of genotoxicity of Cr(VI) compounds. A Cr(IV)-containing compound, a Cr(IV)-ester, was synthesized and used as the first model compound for Cr(IV) studies. Electron spin resonance measurements demonstrated that in the presence of H2O2, this Cr(IV) compound acts as a potent Fenton-like reagent, i.e., it generates OH radical and a Cr(V) species (g = 1.9787) via: Cr(IV) + H2O2-->Cr(V) + OH + OH-. Measurements of OH yield as a function of H2O2 concentration showed that Cr(IV) is more potent than Cr(V) in generating OH. DNA damage assays demonstrate that Cr(IV) and the Cr(IV)/H2O2-generated OH radical can cause DNA strand breaks. The DNA damage caused by OH radical can be effectively blocked by OH radical scavengers. These results thus constitute the first direct evidence for DNA damage by Cr(IV) and Cr(IV)-mediated Fenton-like reaction and support the conjecture that Cr(IV) plays a significant role in the biochemical mechanism of the genotoxic reactions of Cr(VI) compounds and that this effect can be modulated by suitable antiradical agents.

Animals↗

Interleukin-10, interferon gamma, interleukin-2, and soluble interleukin-2 receptor alpha detected during peritonitis in the dialysate and serum of patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: To analyze interleukin (IL)-10, interferon gamma (IFN-gamma), IL-2, and soluble IL-2 receptor alpha (sIL-2R alpha) in the dialysate and serum of patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN AND PATIENTS: Samples from dialysate bags were collected during the initial month of dialysis. During peritonitis, samples were collected from the first three bags on the day of admittance to the hospital and from the night bags on days 3 and 10. Serum samples were drawn on days 1 and 10. RESULTS: IL-10 was detected in all dialysate samples except one on the first day of infection, with a peak median level of 50 pg/mL and a slow decrease thereafter. In serum the median levels never exceeded detectable levels. Patients infected with Escherichia coli or Staphylococcus aureus had higher IL-10 levels in dialysate on day 3 as compared to the remaining patients (p < 0.05). If the catheter had to be drawn, because of persistent cloudy dialysate, the IL-10 levels remained elevated for a longer time (p < 0.05). IFN-gamma and IL-2 were detected only in the dialysate of patients infected with either S. aureus or S. epidermidis. Only one serum sample showed increased IFN-gamma. SIL-2R alpha was found in all the serum and dialysis samples from the first day of infection. Contrary to the analyzed cytokines, the receptor showed severalfold higher levels in serum as compared to the dialysate. During the infection the receptor levels in the dialysate increased, while they remained stationary in the serum, indicating a local production. CONCLUSION: This is the first time IL-10 has been demonstrated in the dialysate during peritonitis in CAPD patients. In view of its role as a suppressor of the immune and inflammatory responses, it is a potentially important observation, which might have clinical implications in the future.

Adult↗