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Biomedical subjects

M Yu

Publications and source records attributed to M Yu.

At least 217 records · Page 12Linked to original sources

High-volume vs standard fluid therapy in a septic pig model. Impact on pulmonary function.

OBJECTIVE: To compare pulmonary function and peripheral organ blood flow in septic pigs receiving high-volume fluid resuscitation or standard-volume fluid resuscitation with similar goals in oxygen delivery. DESIGN: A prospective study comparing 2 groups of septic pigs. SETTING: A university animal research laboratory. SUBJECTS: Eleven septic pigs. INTERVENTIONS: Basal oxygen delivery was increased from 450 to 550 mL/min to at least 600 mL/min by the sixth hour and maintained for 24 hours. From a baseline pulmonary artery occlusion pressure (PAOP) measurement of approximately 6 mm Hg, the high-volume group (n = 5) was treated until a PAOP measurement of 12 mm Hg was reached and the standard-volume group (n = 6) was treated until a PAOP measurement of 8 mm Hg was reached. Blood transfusions and inotropic agents were added as necessary to reach the oxygen delivery goal. RESULTS: The high-volume group had a significantly greater positive fluid balance, greater weight gain, and a higher PAOP but similar intrapulmonary shunt and extravascular lung water as compared with the standard-volume group. CONCLUSION: Resuscitation with large volumes of fluid in early sepsis with a physiological goal of a higher PAOP to augment oxygen delivery did not cause increased pulmonary edema and oxygenation deficit compared with maintenance of lower cardiac filling pressures.

Animals↗

Research on the schizont cell culture vaccine against Theileria annulata infection in Xinjiang, China.

Theileria annulata infection (TAI) is one of the most serious diseases of cattle in Xinjiang Autonomous Region of Uigur Minority Nationality. It has been recorded in 14 prefectures, except the Tulufan Prefecture, but the enzootic areas are mainly distributed around the Zhunger Basin and Talim Basin. According to the records collected in the ten years before vaccination with the schizont cell culture vaccine was carried out, the average incidence rate of TAI in enzootic areas was 7.22% and the mortality rate was 24%. The milk production of cattle suffering from TAI was sharply decreased, and there were usually abortions in pregnant cows. The incidence rate and mortality rate were greater in high grade cattle, so TAI was a constraint to improving cattle breeds. To control this disease effectively in Xinjiang, researchers at the Xinjiang Academy of Animal Science began to study the schizont cell culture vaccine in 1972. In 1977 an immortalised cell line was achieved from a primary cell culture starting with white blood cells from cattle suffering from acute TAI caused by an artificial tick bite. The cell culture medium mainly consisted of calf serum, lactalbumin-hydrolysate, Eagles' medium DMEM and three antibiotics. As a vaccine, the above cells were mixed with preserving medium containing gelatin. This paper describes the experiments on the immunological properties of the vaccine carried out in subsequent years. Up to 1996, vaccine doses for 1,186,150 cattle have been produced and sold. This vaccine has had a critical effect on the control of TAI in Xinjiang. Owing to the sharp decrease in the incidence rate and mortality rate of TAI after cattle were vaccinated, the annual economic benefit of the vaccine is at least 1,620,000 yuan.

Animals↗

Cellular localization and developmental regulation of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) gene expression in the ovine placenta.

This study was designed to examine the cellular localization and developmental regulation of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 gene expression in the ovine placenta. Placental tissues were collected at discrete times between days 59 and 143 of pregnancy (term = 145 days). Levels of 11 beta-HSD1 mRNA were determined by Norther blot analysis. The level of both dehydrogenase and reductase activities of 11 beta-HSD1 was assessed by a radiometric conversion assay using cortisol and cortisone as physiological substrates. The cellular localization of 11 beta-HSD1 protein was determined by standard immunohistochemical technique using a polyclonal antibody specific for the ovine protein. High levels of 11 beta-HSD1 mRNA were detected in the placenta by day 59, and there was a trend towards a decrease between days 98-103 and 125-128 (P = 0.06). The level of placental 11 beta-HSD1 mRNA remained unchanged thereafter. Levels of both 11 beta-HSD1 dehydrogenase and reductase activities followed a similar pattern except that in both cases there was a significant decrease between 98-103 and 125-128 (P < 0.05). Moreover, under the present assay conditions, the dehydrogenase activity was always predominant, suggesting that the net effect of placental 11 beta-HSD1 activity would lead to glucocorticoid inactivation. Thus, the decreased 11 beta-HSD1 activity in the placenta at days 125-128 was consistent with, and may help to explain, the apparent increase in the placental transfer of cortisol from mother to fetus during that time. Throughout pregnancy, intense 11 beta-HSD1 immunoreactivity was detected in fetal trophoblastic cells, maternal stromal cells and blood vessels. In contrast, maternal syncytium was immunonegative before day 125, but became immunopositive thereafter. The observed predominant direction of 11 beta-HSD1 activity in vitro and its pattern of localization in the ovine placenta are consistent with the hypothesis that placental 11 beta-HSD protects the fetus from adverse effects of maternal glucocorticoids by inactivating glucocorticoids locally.

11-beta-Hydroxysteroid Dehydrogenases↗

Metyrapone is a competitive inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 reductase.

The present study was designed to examine the effects of metyrapone in vitro on the activities of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) types 1 and 2, the two intracellular enzymes responsible for the metabolism of glucocorticoids. Enzymatic activities of 11beta-HSD1 and 2 were determined by a radiometric conversion assay using cortisol and cortisone as physiological substrates. The enzyme activity assays were carried out in the absence and presence of metyrapone using sheep liver and kidney microsomes as the source of 11beta-HSD1 and 2, respectively. It was found that metyrapone inhibited the reductase activity of 11beta-HSD1 in a dose-dependent manner with an apparent Ki of 30 microM. Moreover, this inhibition was competitive because the Km for cortisone was increased in the presence of metyrapone. In contrast, metyrapone showed biphasic effects on the dehydrogenase activity of 11beta-HSD1, in that it increased the activity at concentrations lower than 100 microM but decreased it at higher concentrations. However, under similar conditions, metyrapone had little effect on the unidirectional dehydrogenase activity of 11beta-HSD2. In conclusion, the present results provide the first direct evidence that metyrapone is a competitive inhibitor of 11beta-HSD1 reductase, and that it also exerts biphasic effects on 11beta-HSD1 dehydrogenase activity. These findings indicate that metyrapone influences peripheral glucocorticoid metabolism through its regulation of 11beta-HSD1 activity, in addition to its classic inhibitory effects on adrenal steroid biosynthesis. It is therefore imperative that this novel extra-adrenal effect of metyrapone be considered when this drug is used in the diagnosis and treatment of adrenocorticoid-related diseases.

11-beta-Hydroxysteroid Dehydrogenases↗

Intracellular application of hairpin ribozyme genes against hepatitis B virus.

HBV, a partially double-stranded DNA virus, replicates through a pregenomic RNA (pgRNA) intermediate, which provides a therapeutic opportunity for a novel antiviral gene therapy based on ribozyme RNA cleavage. Three hairpin ribozymes (Rzs) were designed which have the potential to disrupt HBV replication by targeting the pgRNA as well as specific mRNAs encoding the HBV surface antigen (HBsAg), the polymerase and the X protein. The ability of each ribozyme to cleave approximately 0.3 kb HBV subgenomic RNA fragments was tested in vitro. Two of the three Rzs tested (BR1 and BR3) were capable of cleaving their respective RNA substrates, while their catalytically disabled mutated counterpart Rzs were not. Structural modifications were performed on these two Rzs, with the goal of increasing catalytic efficiency both in vitro and in cells. To determine the Rz activities in liver cells, the cDNAs for each of the anti-HBV Rzs (and their catalytically disabled negative controls) were cloned into retroviral vectors. Unmodified ribozymes co-expressed with HBV in human liver Huh7 cells reduced the level of viral particle production by up to 66% based on the endogenous polymerase assay, while the structurally modified ribozymes inhibited HBV production up to 83%. These encouraging results indicate the feasibility of ribozyme-mediated gene therapy for the treatment of HBV infections.

Gene Expression↗

Infectivity and pathogenicity in chimpanzees of a surface gene mutant of hepatitis B virus that emerged in a vaccinated infant.

Hepatitis B virus (HBV) variants with amino acid mutations in the a epitope of the major surface protein have been identified, and questions have been raised regarding their biologic properties. Dilutions of serum that contained the first such described HBV mutant, with an Arg-for-Gly substitution at codon 145 of the S gene, were inoculated into 6 seronegative chimpanzees. Five of the animals developed serologic and/or biochemical evidence of hepatitis B. A polymerase chain reaction-based assay that discriminated between the wild type and mutant viral genomes revealed that a pure population of the mutant genome was present in the 10(-6) and 10(-7) dilutions of the index serum, resulting in infection of the chimpanzees receiving these dilutions only with the mutant virus. A clone of the mutant virus replicated normally following transfection in vitro. Thus, this HBV surface gene mutant is viable, infectious, and pathogenic in chimpanzees.

Animals↗

Molecular evolution of the tet(M) gene in Gardnerella vaginalis.

Five clinical isolates of Gardnerella vaginalis known to carry the tetracycline resistance determinant Tet M were examined by hybridization and nucleotide sequencing. Four of the strains carried tet(M) genes with identical sequences. The two versions of the tet(M) gene found in G. vaginalis did not show complete identity with other published tet(M) sequences, but showed mosaic structures with regions of homology to tet(M) gene sequences from Tn916, Tn1545 and the American type plasmid found in Neisseria gonorrhoeae. Hybridization studies showed that all isolates carried the tet(M) gene on a single HindII restriction fragment of variable length. No evidence was found for the presence of sequences homologous to the transposition functions of Tn916.

Base Sequence↗

Evaluation of a continuous cardiac output and mixed venous oxygen saturation catheter in critically ill surgical patients.

OBJECTIVE: To evaluate the agreement of continuous cardiac output and mixed venous oxygen saturation measurements, obtained with a modified pulmonary artery catheter, with those values obtained by standard intermittent bolus thermodilution and cooximetry. DESIGN: Prospective, clinical investigation. SETTING: A surgical intensive care unit in a tertiary referral center. PATIENTS: Twenty-one adult critically ill surgical patients, requiring pulmonary artery catheter monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A modified pulmonary artery catheter capable of continuous monitoring of cardiac output and mixed venous oxygen saturation was used with either an 8.5-Fr or a 9-Fr introducer. At random intervals, the continuous cardiac output measurement was compared with the cardiac output obtained using standard intermittent bolus thermodilution. The system was calibrated every 24 hrs for mixed venous oxygen saturation monitoring. Each saturation obtained by the laboratory cooximeter was compared with that value recorded using the catheter. Data points for 202 pairs of cardiac output (21 patients, 31 catheters) and 65 pairs of mixed venous oxygen saturation (20 patients, 28 catheters) were obtained. The bias and precision of the cardiac output data were 0.49 and 1.01 L/min, respectively. The agreement between the continuous and bolus values decreased as the cardiac output increased. Heart rate did not affect the agreement between the continuous and bolus techniques. The bias and precision of the mixed venous oxygen saturation data were -0.57% and 3.76%, respectively. The hematocrit did not affect the bias or precision of the venous saturation data over the hematocrit range observed (23.2% to 44.6%). Fewer catheter malfunctions were observed when the catheter was used with a 9-Fr introducer than with an 8.5-Fr introducer. CONCLUSIONS: The test catheter adequately measures continuous cardiac output and mixed venous oxygen saturation in the clinical setting. Because intermittent bolus thermodilution is not a true "gold standard" for cardiac output determination, new techniques compared with bolus thermodilution may fail to achieve accuracy expectations. A 9-Fr introducer is recommended, as fiberoptic damage may have occurred when the 8.5-Fr introducer was used.

Adult↗

Renal expression of two rat kallikrein genes under diabetic conditions.

OBJECTIVE: We have reported that bradykinin (BK) excretion is increased in severely diabetic rats, independent of the activity of the main renal kinin-forming enzyme, true kallikrein (KLK). To further investigate the relationship between renal BK excretion and renal KLK in diabetes we studied the regulation of the renal kallikrein-like gene, rat kallikrein 7 (rKLK7), as well as of the KLK encoding gene, rKLK1, in streptozotocin-induced (STZ) diabetic rats. METHODS: Experiments were performed in STZ-induced diabetic male Wistar rats and their non-diabetic controls (n = 7 each group). Twelve weeks after STZ injection, urinary KLK activity, glomerular filtration rate and total protein excretion were determined. After extraction of total renal cortical RNA, specific oligonucleotides were used to generate a reverse transcription-polymerase chain reaction (RT-PCR) products of renal cortical rKLK1 and rKLK7 messenger (m)RNA. Southern blot analysis of these RT-PCR products were hybridized with appropriate gene-specific oligonucleotide probes. RESULTS: After 12 weeks, the rats showed hyperglycemia, proteinuria and a reduced glomerular filtration rate. Renal kininogenase was reduced, as indicated by a reduction in the expression of rKLK1, as well as of the KLK-related gene, rKLK7. CONCLUSIONS: Our data show that the expression of the two principal renal KLK genes is downregulated in the renal cortex of STZ-diabetic rats. We suggest that under severe diabetic conditions the rise in urinary BK excretion is not related to activation of the renal kinin-forming enzyme system.

Actins↗

Ca(2+)-activated Cl- currents are activated by metabolic inhibition in rat pulmonary artery smooth muscle cells.

We report the electrophysiological and functional properties of Ca(2+)-activated Cl- currents [ICl(Ca)] in rat pulmonary artery smooth muscle and the activation of these currents by the metabolic inhibitor cyanide. Caffeine and norepinephrine (NE) evoked both Ca(2+)-activated K+ currents [IK(Ca)] and ICl(Ca) currents in voltage-clamped myocytes (-50 mV). Niflumic acid (10 microM) reduced the caffeine-induced ICl(Ca) by approximately 64% and reversibly reduced NE-induced tension. Exposure of myocytes to cyanide (2-10 mM) induced a slowly developing inward current (-50 mV) in physiological and K(+)-free solutions, which was identified as ICl(Ca) on the basis of ion selectivity and Ca2+ dependence. Cyanide elevated cytosolic Ca2+ concentration, and this elevation was markedly inhibited by preexposure to caffeine and slightly inhibited by nisoldipine. During exposure to caffeine, the Ca(2+)-activated K+ current was also augmented. Cyanide markedly prolonged ICl(Ca) activated by caffeine, increasing the half-decay time from 3.5 (control) to 29 s (cyanide); the half-decay time of the caffeine-induced IK(Ca) was not significantly affected by cyanide. The results indicate that metabolic inhibition increases [Ca2+]i and activates a prolonged, depolarizing Cl- current in pulmonary artery myocytes.

Animals↗

[A comparative study of visual field defects between primary open-angle and low tension glaucoma].

OBJECTIVE: To investigate the characteristics of early visual field defects in primary opene-angle glaucoma (POAG) and low tension glaucoma (LTG). METHOD: The visual fields of 41 eyes with early POAG and 15 eyes with LTG were quantitatively measured with QZS-2 automated perimetry (full threshold program). RESULTS: Most of the early glaucomatous visual field defects in POAG and LTG presented the decrease of localized light sensitivity, and a few indicated the decrease of diffuse type. The defect occurred entirely in the central field and in a small number of eyes it was complicated by the peripheral field defect, especially in the nasal field. The differences of the mean light sensitivity and short-term fluctuation in the central field were statistically significant between the early POAG or LTG and the normal control group (all P < 0.05). In the comparisons of the visual field defect and retinal nerve fiber layer defect between early POAG and LTG groups, the results indicated that the types of damage and distribution of the areas involved were not different. CONCLUSION: The characteristics of early visual field defects in POAG and LTG are the same.

Adult↗

[The effect of IL-2 and IL-3 gene therapy in mice on immunological recovery receiving high dose chemotherapy].

OBJECTIVE: To investigate the effect of Ad-IL-2 and Ad-IL-3 on immunological recovery. METHODS: The Ad-IL-2 and/or Ad-IL-3 were i.p. injected into C57BL/6 mice having received high dose cyclophosphamide (200 mg/kg) 24 hours before. The number and cytotoxicity, Ia antigen expression of peritoneal macrophages, the proliferation and NK cell activity of splenic cells were observed. RESULTS: After i.p. injection with Ad-IL-3, the number, cytotoxicity and Ia antigen expression of peritoneal macrophagee were increased. After i.p. injection with Ad-IL-2, the proliferation and NK cell activity of splenic cells were significantly augmented. As i.p. injection with Ad-IL-2 and Ad-IL-3 simultaneously, both the peritoneal macrophages and splenic cells were activated. CONCLUSION: Intraperitoneal injection of Ad-IL-2 and Ad-IL-3 can promote immune recovery after high dose chemotherapy.

Adenoviridae↗

[Automatic discriminatory analysis of visually evoked potentials waveforms in normals and amblyopes].

We presented a method of discriminatory analysis for the discrimination of P-VEP waveforms in frequency domain, and used this analysis in the discrimination of the P-VEP waveforms of normal eyes and amblyopic eyes. In this analysis, the amplitudes and the phases of the first to the sixth harmonics of P-VEP waveforms were calculated, thus 12 parameters of the P-VEP waveform were obtained for the discriminatory analysis. The P-VEP waveforms of thirty-one normal eyes and thirty-one amblyopic eyes were used to establish the discriminatory system. The result of clinical application showed that this method of Discriminatory Analysis was effective for the discrimination between normal and amblyopic P-VEP.

Amblyopia↗

[Objective assessment of visual acuity with visual evoked potential].

PURPOSE: To study the technique for objectively assessment of visual acuity with Pattern Visual Evoked Potential (PVEP) and Discrete Fourier Transform (DFT). METHOD: Thirty-three normal eyes were tested in this study. Reversal square-wave gratings of eight different sizes (30, 20, 18, 12, 10, 6, 4, 2 min. of arc) were used as stimuli. The reversal rate of the stimuli was 10 times/sec. The harmonic amplitudes of VEP at 10 Hz were calculated with Discrete Fourier Transform. A relation curve between the harmonic amplitude and the size of grating was plotted from the data of each tested eye. Regression line was fitted to the data points in the approximately linear section of the curve which is near the threshold of zero amplitude. The threshold of the grating size was obtained by extrapolating of the regression line to zero amplitude, and the visual acuity was assessed with the threshold. RESULT: In seventy percent of tested eyes, the visual acuities assessed with VEPs were consistent with those measured with the International Standard Test Chart. CONCLUSION: The VEP technique for visual acuity assessment is reliable.

Adolescent↗

Variation of the multifocal visual evoked potential with eccentricity in isometropic amblyopes.

PURPOSE: To investigate the variation of visual function in different eccentricities of the visual field in isometropic amblyopes. METHOD: The stimulus matrix containing 61 hexagons was generated on a monitor. The diameter of the entire stimulating field was approximately 13.6 deg of arc; the frame rate of the monitor was 67 Hz. Every hexagon of the display contained a number of black and white small hexagonal patches which reversed during stimulation. These hexagons were simultaneously but independently modulated in time by the controlling computer program. The flashed elements were selected differently on each frame according to a computer-generated binary pseudo-random time series (m-sequence); the response contributions from each of the individual stimulus elements could be extracted from the cross corre-ation function. Subjects were asked to maintain fixation at the center of the stimulus pattern while each of the hexagons of the display reversed. The VERIS system extracted the local responses by cross-correlating the input (binary m-sequence) and output (evoked response) signals. The latencies and amplitudes of the responses from the central 8.6 deg of arc in the visual field were analyzed. RESULT: Mean latency is about 22 ms longer at the fovea, and 10 ms longer in the first ring for the isometropic amblyopes than for the normal (control) subjects. The differences are highly significant at the fovea and in the first ring. In the second ring and the third ring, the difference have reduced to 3 to 4 ms. The latencies at the second ring and the third ring are not significantly different. In isometropic amblyopes, the P1-N2 amplitude is about half of that in the normal subjects for the fovea and is similar to that for the normal subjects in the third ring. The P1-N2 amplitudes in the isometropic amblyopes are significant lower than the normal values from the center to the second ring. CONCLUSION: In isometropic amblyopia, the prolongation of latencies and the attenuation of the amplitudes of topographic VEPs are marked in the central region of the visual field and diminished in the periphery. The topographic VEP can objectively reflect the variation of visual response with eccentricity in the visual field.

Adolescent↗