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Biomedical subjects

W Tang

Publications and source records attributed to W Tang.

At least 163 records · Page 9Linked to original sources

Detection of disease-specific augmentation of abnormal immunoglobulin G in sera of patients with rheumatoid arthritis.

Galactose-free immunoglobulin G (IgG), which is known to be higher in the sera of patients with rheumatoid arthritis, was prepared from IgG of healthy volunteers using enzymes. Its reactivity to lectins was analyzed. The galactose-free IgG showed no reactivity to Ricinus communis agglutinin 120 but displayed greater reactivity to concanavalin A and Lens culinaris lectin than did intact human IgG. Then, IgG in serum samples was bound to protein A immobilized on a nitrocellulose membrane, and its reactivity to biotinylated concanavalin A was measured with streptavidin-conjugated horseradish peroxidase. When the reactivity to concanavalin A of IgG in sera from healthy individuals and patients with rheumatoid arthritis (RA), osteoarthritis, systemic lupus erythematosus, or hepatic disease was compared, higher levels were shown in patients with RA, notably in 60% of the seronegative patients and 80% of the early phase patients. Therefore, it was suggested that augmentation of the abnormal IgG in sera was highly specific to patients with RA and that this novel serum test could be very useful for an accurate diagnosis of this disease.

Arthritis, Rheumatoid↗

Translocation of the zinc finger protein basonuclin from the mouse germ cell nucleus to the midpiece of the spermatozoon during spermiogenesis.

Basonuclin was first described as a human keratinocyte zinc finger protein present in the nuclei of proliferative basal keratinocytes in the epidermis. It disappears from keratinocytes that have lost their proliferative ability and have entered terminal differentiation. We now report that basonuclin is present also in the germ cells of the mouse testis and ovary. Immunocytochemical staining detected basonuclin in the nuclei of spermatogonia and spermatocytes at various developmental stages. During spermiogenesis, it relocated from the nucleus to the midpiece of the flagellum of the spermatozoa. In the ovary, basonuclin was found mainly in the nuclei of developing oocytes. The dual presence of basonuclin in differentiated spermatozoa and oocytes suggests that it may play a role in their differentiation and the early development of an embryo.

Animals↗

Decreases in organ blood flows associated with increases in sublingual PCO2 during hemorrhagic shock.

Earlier studies demonstrated that not only the stomach but also the esophageal wall served as an appropriate site for estimating the severity of circulatory shock by using tonometric methods. We then conceived of the option of sublingual tonometry. In the present study, we tested the hypothesis that the changes in sublingual PCO2 serve as indicators of decreases in blood flow to sublingual and visceral tissue. In Sprague-Dawley rats, sublingual PCO2 increased from 50 to 127 Torr and arterial blood lactate increased from 0.9 to 11.2 mmol/l during bleeding. Sublingual blood flow simultaneously decreased to approximately 32% of preshock values. After reinfusion of shed blood, organ blood flows and sublingual PCO2 were promptly restored to near-baseline values. There were corresponding decreases in blood flows in the tongue, stomach, jejunum, colon, and kidneys during hemorrhagic shock. Increases in sublingual PCO2 were highly correlated with decreases in sublingual blood flow (r = 0.80), tongue blood flow (r = 0.81), gastric blood flow (r = 0.74), jejunal blood flow (r = 0.65), colon blood flow (r = 0.80), and renal blood flow (r = 0.75). Unbled control animals demonstrated no significant changes. Therefore, we anticipate that sublingual tonometry will provide a useful, noninvasive alternative for monitoring visceral PCO2.

Animals↗

Sublingual capnometry for diagnosis and quantitation of circulatory shock.

We investigated sublingual tissue PCO2 during hemorrhagic and septic shock. Hemorrhagic shock was induced in 10 rats. Sublingual PCO2 increased from 45 to 125 mm Hg and arterial pressure declined from 138 to 49 mm Hg, end-tidal PCO2 decreased from 35 to 13 mm Hg, and cardiac index fell from 290 to 77 ml/min/kg. Arterial blood lactate increased from 0.9 to 15.8 mmol/L. Gastric PCO2 was measured in five animals and it increased from 46 to 87 mm Hg. No significant changes were observed in eight "sham" bled animals including the five animals in which gastric PCO2 was measured. Highly significant linear correlations (p < 0.001) between sublingual PCO2 and gastric PCO2 (r = 0.71), cardiac index (r = -0.74), and arterial lactate (r = 0.59) were documented. We subsequently investigated sublingual PCO2 in five animals in which sepsis was induced by intravenous infusion of live Staphylococcus aureus. Like hemorrhagic shock, highly significant linear correlations were observed between end-tidal PCO2 and cardiac index and between sublingual PCO2 and arterial blood lactate. Sublingual PCO2 promises to serve as a technically simple, noninvasive, and rapid response quantitator of severity of circulatory shock states.

Animals↗

Tissue hypercarbic acidosis as a marker of acute circulatory failure (shock).

Measurement of pH of the stomach wall (gastric intramural pH) by the tonometric method has been utilized both experimentally and clinically as an indicator of the capability of the stomach to extract and utilize oxygen. As such, it serves as a metabolic marker of acute perfusion failure (circulatory shock). More recently, researchers have found that increases in the PCO2 accounted for the decline in pH; this was documented in tissues other than the stomach wall, including the esophageal and sublingual mucosa. In this review, tissue PCO2 is identified as a universal indicator of impaired perfusion and contrasted with conventional hemodynamic and metabolic markers of perfusion failure.

Acidosis↗

Binding specificities of lectins to immobilized glycoproteins and oligosaccharides differ from those of immobilized lectins to oligosaccharides.

The carbohydrate-binding specificities of lectins in solution to glycoproteins and neoglycolipids immobilized on a solid phase were analyzed in order to establish a simple, rapid method for structural analysis of the carbohydrate moieties of small amounts of individual glycoproteins blotted on membrane. Eight glycoproteins containing typical O-linked tetrasaccharides or a series of typical N-linked oligosaccharides of the high-man-nose type, hybrid type, and complex type and 6 neoglycoproteins containing mono- or di-saccharides were dot blotted on membranes and the membranes were then reacted with 8 kinds of horseradish peroxidase-conjugated lectins before and after heat treatment. Neoglycolipids containing the glycoprotein-derived oligosaccharides immobilized on a thin layer chromatography plate were also reacted with lectins. The heat treatment of the membrane increased lectin reactivity toward the glycoproteins. The carbohydrate-binding behavior of lectins, Phaseolus vulgaris erythroagglutinin, wheat germ agglutinin, and concanavalin A in solution toward glycoproteins and neoglycolipids immobilized on a solid phase differed from that of immobilized lectins toward oligosaccharides in solution. This difference should be noted in lectin detection of specific carbohydrates of individual glycoproteins on membrane.

Glycoproteins↗

[A model of nasopharyngeal carcinoma with spontaneous highly lymphatic metastasis in nude mice and its biological characteristics].

OBJECTIVES: To establish a model of nasopharyngeal carcinoma with spontaneous highly lymphatic metastasis in nude mice and to study its biological characteristics. METHODS: The clone cells of nasopharyngeal carcinoma(NPC), CNE-2Z-H5, were inoculated into nude mice. The cancer cells of lymph node metastatic foci were transplanted into nude mice again when the metastasis of nude mice were observed. After repetition of this procedure for 9 cycles, the metastatic rate and the metastatic paths were observed in nude mice of every passage; The changes were also observed in proliferation ability, expression of growth factor and its receptor in vitro, proliferation index(PI), and tumor weight and doubling time of the transplantable tumor in every passage in vivo. RESULTS: The lymphatic metastatic rates were higher than 85%. The metastatic paths were single, the proliferation ability was increased in cancer cells of every passage in vivo and vitro after passaging cancer cells of lymphatic metastatic foci for 9 cycles in nude mice. CONCLUSIONS: A model of nasopharyngeal carcinoma with spontaneous highly lymphatic metastasis has been established in nude mice, and the possibilities of metastasis and proliferation are increased after progression of NPC cells in nude mice. There is a close relationship between the metastasis and proliferation in NPC.

Animals↗

[The relationship between chromatographic retention value and grey model parameters].

The relationship between development parameter a, grey action variable u in the grey model GM(1,1) and parameters A,B which express the relation of k' and phi, that is, 1nk' = A + B phi have been studied. The functions of these two kinds of parameters which are a = -B lambda and u = B lambda eA[(1 - e-B lambda)(-1) - 1] are given. Therefore, it can predict the position of peaks and the possibility of separating the components in different mixtures. It verifies the experimental data, and gives out a proper method to amend equations. The results show that the function is fit for not only the research of chromatographic parameters of explosives but also the prediction of A,B values of other compounds.

Chromatography↗

Effect of transtympanic injection of steroids on cochlear blood flow, auditory sensitivity, and histology in the guinea pig.

HYPOTHESIS: Transtympanic application of steroids is not harmful to the inner ear. BACKGROUND: Steroids are routinely used to treat inner ear pathologies, such as sudden sensorineural hearing loss and autoimmune inner ear disease. The transtympanic route has received increased attention as it can lead to higher levels in tissue and nearly eliminate systemic effects. There has been concern over the safety of applying these drugs directly to the inner ear. METHODS: This study investigates the effects of transtympanic Dexamethasone injection on cochlear blood flow using laser Doppler flowmetry, auditory sensitivity using auditory brain stem responses, and histology in the guinea pig. RESULTS: Results show a significant increase in cochlear blood flow within 30 s to a mean of 29.26% without significant change in auditory sensitivity. The increase in cochlear blood flow was sustained and did not return to baseline for at least 1 hour after drug application. No histologic changes were observed. CONCLUSIONS: These results suggest that transtympanic steroid application is not likely to be detrimental to the inner ear. Additionally, the increase in blood flow may indicate a possible mechanism accounting for the pharmacologic effects of steroids in the inner ear.

Animals↗

Novel steroid-linked conjugates of 17 beta-[N-[N'-(2-chloroethyl)-N'-nitroso]carbamoyl]amino acids and their antineoplastic activity against Noble Nb prostate carcinoma model in rats.

The novel steroid conjugates 17 beta-[N-[N'-(2-chloroethyl)-N'-nitroso] carbamoyl]-glycyl-19-nortestosterone (1) and 17 beta-[N-[N'-(2-chloroethyl)-N'-nitroso]carbamoyl]-L-alyanyl-19- nortestosterone (2) were synthesized and characterized with respect to affinity for steroid receptors and for androgenic efficacy. At an i.p. dosage of 50 mg/kg, conjugates 1 and 2 induced strong tumor inhibition of Nobel Nb prostate carcinoma in rats, but also a marked loss of body weight. In two further experiments, treatment with conjugate 2 at a dosage of 25 mg/kg demonstrated high antitumor activity without indication of toxicity. Conjugate 2 achieved the same tumor growth inhibition as a nearly twofold molar dose of cyclophosphamide. The results indicate reproducibly high antitumor activity of 2 in the Noble Nb model at a well tolerated dosage. A low dose equimolar mixture of unlinked N-(2-chloroethyl)-N-nitrosocarbamoyl (CNC)-alanine and 19-nortestosterone was significantly more toxic than conjugate 2, showing about the same adverse effect on the body weight as the conjugate at high dosage. CNC-L-alanine at equimolar dosage was highly toxic, causing early death of all animals.

Amino Acids↗

Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes.

Standard overexpression transgenic approaches are limited in their ability to model waxing and waning diseases and frequently superimpose development-dependent and -independent phenotypic manifestations. We used the clara cell 10-kD protein (CC10) promoter and the reverse tetracycline transactivator (rtTA) to create a lung-specific, externally regulatable, overexpression transgenic system and used this system to express human interleukin 11 (IL-11) in respiratory structures. Gene induction could be achieved in utero, in neonates and in adult animals. Moreover, gene expression could be turned off by removal of the inducing stimulus. When gene activation was initiated in utero and continued into adulthood, subepithelial airway fibrosis, peribronchiolar mononuclear nodules, and alveolar enlargement (emphysema) were noted. Induction in the mature lung caused airway remodeling and peribronchiolar nodules, but alveolar enlargement was not appreciated. In contrast, induction in utero and during the first 14 d of life caused alveolar enlargement without airway remodeling or peribronchiolar nodules. Thus, IL-11 overexpression causes abnormalities that are dependent (large alveoli) and independent (airway remodeling, peribronchiolar nodules) of lung growth and development, and the CC10-rtTA system can be used to differentiate among these effector functions. The CC10-rtTA transgenic system can be used to model waxing and waning, childhood and growth and development-related biologic processes with enhanced fidelity.

Aging↗

Identification of a flexible loop region (297-313) of urokinase-type plasminogen activator, which helps determine its catalytic activity.

Pro-urokinase has a much higher intrinsic catalytic activity than other zymogens of the serine protease family. Lys300(c143) in an apparent "flexible loop" region (297-313) was previously shown to be an important determinant of this intrinsic catalytic activity. This was related to the loop allowing the positive charge of Lys300(c143) to transiently interact with Asp355(c194), thereby inducing an active conformation of the protease domain (Liu, J. N., Tang, W., Sun, Z., Kung, W., Pannell, R., Sarmientos, P., and Gurewich, V. (1996) Biochemistry 35, 14070-14076). To further test this hypothesis, the charge at position 300(c143) and the flexibility of the loop were altered using site-directed mutagenesis designed according to a computer model to affect the interaction between Lys300(c143) and Asp355(c194). When the charge at Lys300(c143) but not Lys313(c156) was reduced, a significant reduction in the intrinsic catalytic activity occurred. Similarly, when the flexibility (wobbliness) of the loop was enhanced reducing the size of side chain, the intrinsic catalytic activity was also reduced. By contrast, when the loop was made less flexible, the intrinsic catalytic activity was increased. These findings were consistent with the hypothesis. The effects of these mutations on two-chain activity were less and often discordant with the intrinsic catalytic activity, indicating that they can be modulated independently. This structure-function disparity can be exploited to create a more zymogenic pro-urokinase (lower intrinsic catalytic activity) with a high catalytic activity, as exemplified by two of the mutants. The changes in intrinsic catalytic activity and two-chain activity induced by the mutations were due to changes in kcat rather than Km. Some significant structure-function differences between pro-urokinase and its highly homologous counterpart, tissue plasminogen activator, were also found.

Catalysis↗

Ethnic origin and serum levels of 1alpha,25-dihydroxyvitamin D3 are independent predictors of coronary calcium mass measured by electron-beam computed tomography.

BACKGROUND: Blacks have been found to have lower amounts of coronary calcium as well as higher levels of the osteoregulatory steroid 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] than whites. We sought to determine if racial differences in coronary calcium mass could be explained by differences in serum levels of 1,25(OH)2D3. METHODS AND RESULTS: We evaluated standard coronary risk factors, quantified coronary calcium mass with electron-beam computed tomography (EBCT), and measured serum 1,25(OH)2D3 with radioimmunoassay in 283 high-risk subjects (51 [180%] black, 232 [82%] white). Black subjects had lower masses of coronary calcium than whites (14 versus 47 mg; P=.003). Serum 1,25(OH)2D3 levels were slightly higher in blacks (41 versus 38 pg/mL; P=.05). Log 1,25(OH)2D3 levels were inversely proportional to log-transformed calcium mass (r=-.19; P=.001) in both races. Multivariate linear regression demonstrated that both black race (P=.02) and 1,25(OH)2D3 levels (P=.007) contributed inversely and independently to coronary calcium mass. However, an interaction term of racex1,25(OH)2D3 did not significantly contribute to coronary calcium mass, indicating that other undetermined factors in addition to 1,25(OH)2D3 are responsible for ethnic differences in coronary calcium mass. CONCLUSIONS: Both black race and serum levels of 1,25(OH)2D3 are independent negative determinants of coronary calcium mass. Nevertheless, diminished amounts of coronary calcium in blacks are not accounted for by higher 1,25(OH)2D3 levels.

Aged↗

Electron beam computed tomographic coronary calcium as a predictor of coronary events: comparison of two protocols.

BACKGROUND: We assessed the accuracy of two electron beam computed tomography (EBCT) protocols for predicting coronary events. METHODS AND RESULTS: In 1994, 24 months after enrollment in a longitudinal study, 326 high-risk adults underwent both 3- and 6-mm image-slice thickness EBCT scanning and were followed up for 32.0+/-4.0 additional months. Events were defined as either coronary death, myocardial infarction, or revascularization. We monitored these subjects for the 32-month postscanning period with yearly phone calls and acquisition of records for all hospital admissions. At the time of scanning, 11 subjects (3%) had already suffered 12 events (5 infarctions and 7 revascularizations) during the 24-month prescanning period. During the postscanning period, 18 subjects (6%) suffered 23 events (5 coronary deaths, 6 infarctions, and 12 revascularizations). Thus, 28 subjects (9%) suffered 35 events. Calcium quantities calculated for both protocols, performed on the same subjects, were sorted in ascending order and divided into equal quartiles. When revascularizations were included, there was a significant trend toward higher frequencies of events with increasing calcium quantity (P<.01). However, coronary death and infarction were not significantly more frequent in higher quartiles. These relationships were preserved in the subjects without prior events at the time of scanning. CONCLUSIONS: Calcium quantities from the 3-mm and the more reproducible 6-mm scanning are equally accurate for predicting events. Coronary calcium amount appears to be a weak predictor of coronary death and infarction. Its predictive accuracy is superior for predicting revascularization.

Aged↗

Two-dimensional analysis of recombinant E. coli proteins using capillary isoelectric focusing electrospray ionization mass spectrometry.

On-line combination of capillary isoelectric focusing with electrospray ionization mass spectrometry is applied for a two-dimensional analysis of Escherichia coli proteins. The proteins are focused and cathodically mobilized in a polyacrylamide coated capillary. At the end of the capillary, various protein zones are analyzed by mass spectrometry coupled through an electrospray interface. Comparisons with silver-stained two-dimensional gel electrophoresis are made with regard to mass determination, resolution, speed, and sensitivity. Direct identification of a recombinant fusion protein of glutathione S-transferase and striped bass growth hormone is achieved without any prior protein isolation procedures.

Ampholyte Mixtures↗

High-energy defibrillation increases the severity of postresuscitation myocardial dysfunction.

BACKGROUND: The fatal outcome of victims after initially successful resuscitation from cardiac arrest has been attributed both to global myocardial ischemia during the interval of cardiac arrest and to the adverse effects of reperfusion. The present study was prompted by earlier experimental observation that the magnitude of myocardial dysfunction was in part related to the energy delivered during electrical defibrillation. METHODS AND RESULTS: Ventricular fibrillation (VF) was induced in 15 Sprague-Dawley rats. Precordial compression was begun together with mechanical ventilation after 4 minutes of untreated VF and continued for 6 minutes. Spontaneous circulation was restored in each animal after external defibrillation with a single stored 2-, 10-, or 20-J countershock. Cardiac index and the rate of left ventricular pressure rise at left ventricular pressure of 40 mm Hg (dP/dt40) and fall (negative dP/dt) during the 240-minute interval after successful resuscitation were decreased, and left ventricular diastolic pressure was increased. These decreases in myocardial function were closely related to the energy of electrical defibrillation. After a 20-J shock, animals survived for only 5+/-3 hours; after a 10-J shock, animals survived for 15+/-4 hours; and after a 2-J shock, all animals survived for >24 hours. CONCLUSIONS: The severity of postresuscitation myocardial dysfunction is related, at least in part, to the magnitude of the electrical energy of the delivered shock.

Animals↗

Dosimetric comparison of treatment planning systems in irradiation of breast with tangential fields.

PURPOSE: The objectives of this study are: (1) to investigate the dosimetric differences of the different treatment planning systems (TPS) in breast irradiation with tangential fields, and (2) to study the effect of beam characteristics on dose distributions in tangential breast irradiation with 6 MV linear accelerators from different manufacturers. METHODS AND MATERIALS: Nine commercial and two university-based TPS are evaluated in this study. The computed tomographic scan of three representative patients, labeled as "small", "medium" and "large" based on their respective chest wall separations in the central axis plane (CAX) were used. For each patient, the tangential fields were set up in each TPS. The CAX distribution was optimized separately with lung correction, for each TPS based on the same set of optimization conditions. The isodose distributions in two other off-axis planes, one 6 cm cephalic and the other 6 cm caudal to the CAX plane were also computed. To investigate the effect of beam characteristics on dose distributions, a three-dimensional TPS was used to calculate the isodose distributions for three different linear accelerators, the Varian Clinac 6/100, the Siemens MD2 and the Philips SL/7 for the three patients. In addition, dose distributions obtained with 6 MV X-rays from two different accelerators, the Varian Clinac 6/100 and the Varian 2100C, were compared. RESULTS: For all TPS, the dose distributions in all three planes agreed qualitatively to within +/- 5% for the "small" and the "medium" patients. For the "large" patient, all TPS agreed to within +/- 4% on the CAX plane. The isodose distributions in the caudal plane differed by +/- 5% among all TPS. In the cephalic plane in which the patient separation is much larger than that in the CAX plane, six TPS correctly calculated the dose distribution showing a cold spot in the center of the breast contour. The other five TPS showed that the center of the breast received adequate dose. Isodose distributions for 6 MV X-rays from three different accelerators differed by about +/- 3% for the "small" patient and more than +/- 5% for the "large" patient. For two different 6 MV machines of the same manufacturer, the isodose distribution agreed to within +/- 2% for all three planes for the "large" patient. CONCLUSION: The differences observed among the various TPS in this study were within +/- 5% for both the "small" and the "medium" patients while doses at the hot spot exhibit a larger variation. The large discrepancy observed in the off-axis plane for the "large" patient is largely due to the inability of most TPS to incorporate the collimator angles in the dose calculation. Only six systems involved agreed to within +/- 5% for all three patients in all calculation planes. The difference in dose distributions obtained with three accelerators from different manufacturers is probably due to the difference in beam profiles. On the other hand, the 6 MV X-rays from two different models of linear accelerators from the same manufacturer have similar beam characteristics and the dose distributions are within +/- 2% of each other throughout the breast volume. In general, multi-institutional breast treatment data can be compared within a +/- 5% accuracy.

Body Constitution↗

The structure of the gene for murine CTP:phosphocholine cytidylyltransferase, Ctpct. Relationship of exon structure to functional domains and identification of transcriptional start sites and potential upstream regulatory elements.

Phosphatidylcholine (PC) is the most abundant eukaryotic phospholipid and serves critical structural and cell-signaling functions. CTP:phosphocholine cytidylyltransferase (CT) is the rate-limiting enzyme in the CDP-choline pathway of PC biosynthesis, which is utilized by all tissues and is the sole or major PC biosynthetic pathway in all non-hepatic cells. Herein, we present the complete structure of the murine CT (Ctpct) gene. One P1 genomic clone and six subsequent plasmid subclones were isolated and analyzed for the exon-intron organization of the Ctpct gene. The gene spans approximately 26 kilobases and is composed of 9 exons and 8 introns. The exons match the distinct functional domains of the CT enzyme: exon 1 is untranslated; exon 2 codes for the nuclear localization signal domain; exons 4-7 encompass the catalytic domain; exon 8 codes for the alpha-helical membrane-binding domain; and exon 9 includes the C-terminal phosphorylation domain. Two transcriptional initiation sites, spaced 35 nucleotides apart, were identified using 5'-rapid amplification of cDNA ends polymerase chain reaction. The 5' natural flanking region was found to lack TATA or CAAT boxes and to contain GC-rich regions, which are features typical of promoters of housekeeping genes. Several sites that have the potential to interact with transcription regulatory factors, such as Sp1, AP1, AP2, AP3, Y1, and TFIIIA, were identified in the 5'-region of the gene and found to be distributed in two distinct clusters. These data will provide the basis for future studies on the cis- and trans-acting factors involved in Ctpct gene transcription and for the creation of induced mutant mouse models of altered CT activity.

Animals↗