Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 721 records · Page 40Linked to original sources

PubMed1997

Activated protein C resistance and anticardiolipin antibodies in patients with venous leg ulcers.

BACKGROUND: Hypercoagulable states, which include the presence of anticardiolipin antibodies (ACAs), have been associated with skin ulceration. Resistance to activated protein C (APC), resulting from the factor V Leiden mutation, is a common risk factor for venous thrombosis. Its prevalence among patients with venous leg ulcers is not known. OBJECTIVE: Our purpose was to determine the prevalence of factor V Leiden and ACA in patients with venous leg ulceration. METHODS: Twenty-nine consecutive patients with venous leg ulcers were studied. Resistance to APC was first determined by functional assay based on the partial thromboplastin time. Patients with an abnormally low APC ratio were then subjected to molecular analysis for confirmation of factor V Leiden. Measurements of ACA were performed by enzyme-linked immunosorbent assay. RESULTS: APC resistance was detected in 11 of 26 patients. However, only 2 of these 11 patients (7.7% overall) were found to be heterozygous for the factor V Leiden mutation. ACA was present in neither patient with the Leiden mutation but was found in 6 of 21 patients tested (29% overall). CONCLUSION: The factor V Leiden mutation, unlike ACA, may not be more prevalent in patients with venous leg ulcers than in the general population. Our results emphasize the importance of molecular analysis for factor V Leiden in patients with APC resistance.

Adult↗

PubMed1997

Direct assay and shelf-life monitoring of aspirin tablets using Raman spectroscopy.

A comparison was made between Raman and high-performance liquid chromatography (HPLC) analysis of aspirin tablets. The basis was an assay of aspirin content and the determination of salicylic acid produced by decomposition. Raman observations were performed directly on both intact and powdered tablet material. The limit of detection of HPLC with an ultraviolet detector is lower than that of the Raman measurement, but both are adequate for this application. The reproducibility of the Raman measurement is somewhat better than that of the HPLC measurement. Both methods were used in a degradation study in which samples were stored in a humid atmosphere for a maximum period of 8 weeks. Aside from somewhat higher salicylic acid responses from the HPLC method, which were attributed to hydrolysis during chromatography, results from the two methods were comparable. Direct Raman measurements are faster and do not require the use of solvents.

Anti-Inflammatory Agents↗

PubMed1997

The epidemiology of thyroid disease and implications for screening.

The burden of thyroid disease in the general population is enormous. As many as 50% of people in the community have microscopic nodules, 3.5% have occult papillary carcinoma, 15% have palpable goiters, 10% demonstrate an abnormal thyroid-stimulating hormone level, and 5% of women have overt hypothyroidism or hyperthyroidism. Despite this high prevalence of thyroid disease, screening for these disorders is not recommended by any major health agency. This article explores the epidemiologic issues surrounding this complex problem by analyzing prevalence, incidence, and mortality data from a worldwide variety of sources.

Adult↗

PubMed1997

V(D)J recombination in Ku86-deficient mice: distinct effects on coding, signal, and hybrid joint formation.

Ku, a heterodimer of 70 and 86 kDa subunits, plays a critical but poorly understood role in V(D)J recombination. Although Ku86-deficient mice are defective in coding and signal joint formation, rare recombination products have been detected by PCR. Here, we report nucleotide sequences of 99 junctions from Ku86-deficient mice. Over 90% of the coding joints, but not signal or hybrid joints, exhibit short sequence homologies, indicating that homology is required to join coding ends in the absence of Ku86. Our results suggest that Ku86 may normally have distinct functions in the formation of these different types of junctions. Furthermore, Ku86(-/-) joints are unexpectedly devoid of N-region diversity, suggesting a novel role for Ku in the addition of N nucleotides by terminal deoxynucleotidyl transferase.

Animals↗

PubMed1997

Stem cells of the corneal epithelium lack connexins and metabolite transfer capacity.

The stem cells of the corneal epithelial lineage are confined to the basal cell layer of the limbus, a vascularized outer corneal rim. These slow cycling cells of great proliferative potential maintain the corneal epithelial mass. Since cell-cell communication plays an important role in development and differentiation, we conducted a comparative examination of the expression of two corneal connexins, C x 43 and C x 50, and the tracer transfer capacity of the limbal and corneal epithelia using the scrape loading technique. C x 43 is abundantly expressed in the basal cell layer of the epithelium covering the cornea, but is essentially absent from the mouse, human, neonatal rabbit, and chicken limbal epithelium. In the adult rabbit the limbal epithelium displays an overall weak C x 43 immunoreactivity, but C x 43-free isolated basal cells can be distinguished. C x 50 is expressed throughout the corneal epithelium of the three mammalian corneas, but is not detectable in the limbus. Scrape loading experiments in the rabbit yielded results which were consistent with the immunohistological findings; limbal epithelium lacked tracer (lucifer yellow) transfer capacity, strongly suggesting the absence of functional gap junctions. Altogether, our results demonstrate the incompetence of stem cells for gap junction-mediated cell-to-cell communication. This property may reflect the need of these unique cells to maintain a distinct intracellular environment.

Aged↗

PubMed1997

Temporal and Quantitative Analysis of Chimerism in Liver and Kidney Transplant Patients: An Enhanced Fluorescence Detection System Allows for More Sensitive Quantitative Detection.

Background: Because spontaneous microchimerism has been reported in stable renal and hepatic allografts, the presence of donor-derived cells in recipient tissues was investigated in kidney and liver tranplant recipients. Methods and Results: Human lymphocyte antigen class II markers and Y-chromosome sequences in male donor-to-female recipient transplants were used for chimeric analysis. Human lymphocyte antigen typing was performed by group-specific polymerase chain reaction amplification and restriction fragment length polymorphism analysis, X-chromosome- and Y-chromosome-specific primers were used in a multiplex polymerase chain reaction analysis. Quantitative Y-chromosome analysis was performed using energy-transfer fluorescence from a nested primer system. Patients who had rejected their grafts were also analyzed, as were a group who were analyzed for chimerism at the time of transplant (day 1) and sequentially at various intervals for up to 3 months. Of 23 long-term kidney patients analyzed, 16 were chimeric by human lymphocyte antigen or sex-determination analysis. In 2 patients whose graft had failed no chimerism was observed. Chimerism in liver patients was detectable on the day of transplant and was maintained for 30 to 120 days as measured at 5-day intervals (these patients continue to be monitored). Quantititative analysis suggested that the ratio of donor to recipient cells was variable in a patient and ranged from greater than 1 in 10(4) to less than 1 in 10(5). An enhanced fluorescence energy-transfer detection system was adopted to increase sensitivity of the polymerase chain reaction detection of chimerism and to quantitate the results. Conclusions: The results indicate that cells from the donor organ migrate into recipient tissues early after transplantation. These cells persist in a majority of patients for at least 3 to 4 years. It has been proposed that tolerance is related to the presence of these "passenger" leukocytes and that dendritic cells play the most important role. The data suggest that the establishment of chimerism plays an important role in graft acceptance in a majoritiy of the kidney and liver patients in this study. These findings also suggest that the levels of chimeric cells, "a quantitative chimerism," may be important in establishing tolerance but further studies are required to support this contention.

Journal Article↗

PubMed1997

Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells.

Thirteen isoflavonoids, flavonoids, and lignans, including some known phytoestrogens, were evaluated for their effects on DNA synthesis in estrogen-dependent (MCF-7) and -independent (MDA-MB-231) human breast cancer cells. Treatment for 24 hours with most of the compounds at 20-80 microM sharply inhibited DNA synthesis in MDA-MB-231 cells. In MCF-7 cells, on the other hand, biphasic effects were seen. At 0.1-10 microM, coumestrol, genistein, biochanin A, apigenin, luteolin, kaempferol, and enterolactone induced DNA synthesis 150-235% and, at 20-90 microM, inhibited DNA synthesis by 50%. Treatment of MCF-7 cells for 10 days with genistein or coumestrol showed continuous stimulation of DNA synthesis at low concentrations. Time-course experiments with genistein in MCF-7 cells showed effects to be reversed by 48-hour withdrawal of genistein at most concentrations. Induction of DNA synthesis in MCF-7 cells, but not in MDA-MB-231 cells, is consistent with an estrogenic effect of these compounds. Inhibition of estrogen-dependent and -independent breast cancer cells at high concentrations suggests additional mechanisms independent of the estrogen receptor. The current focus on the role of phytoestrogens in cancer prevention must take into account the biphasic effects observed in this study, showing inhibition of DNA synthesis at high concentrations but induction at concentrations close to probable levels in humans.

Anticarcinogenic Agents↗

PubMed1997

Dysprosium-enhanced MR imaging for tumor tissue characterization. An experimental study in a human xenograft model.

PURPOSE: To evaluate dysprosium-enhanced MR imaging for differentiation between morphologically intact and necrotic tumor tissue in a tumor model. MATERIAL AND METHODS: A human colon carcinoma was transplanted subcutaneously into 9 nude (immunodeprived) rats. MR imaging was performed before and after injection of the dysprosium agent Dy-DTPA-BMA. T1-, T2- and T2*-weighted sequences were acquired. The tumors were dissected, histological sections were prepared, and compared with corresponding MR images. RESULTS: In intact tissue, the MR signal intensity in the T2- and T2*-weighted images decreased after Dy injection and the delineation of the intact regions were sharp and corresponded well to the gross histological sections. CONCLUSION: Dy-enhanced MR imaging facilitated the differentiation between intact and necrotic tumor tissue.

Adenocarcinoma↗

PubMed1997

Diagnostic efficacy of MnDPDP in MR imaging of the liver. A phase III multicentre study.

PURPOSE: To assess the diagnostic efficacy, safety and tolerability of mangafodipir trisodium (MnDPDP, Teslascan) in MR imaging of the liver. MATERIAL AND METHODS: Eighty-two patients from 4 centres underwent MR imaging with pre-contrast sequences including T1-weighted SE and GRE, and T2-weighted turbo SE sequences. MnDPDP at a dose of 5 mumol/kg b.w. was administered by slow i.v. infusion, and 20-60 min after infusion the T1-weighted SE and GRE sequences were repeated. Diagnostic efficacy was evaluated by counting the number of lesions and by evaluating whether more information for lesion characterisation was available in post-contrast images. Safety and tolerability were assessed by recording adverse events and infusion-related discomfort. RESULTS: Significantly more lesions were found in MnDPDP-enhanced T1-weighted SE and GRE images than in unenhanced images of the same sequences. More lesions were also found in these images compared with T2-weighted images at a level of marginal significance. More information was obtained from MnDPDP-enhanced images in 40 cases. Mild to moderate adverse events were experienced by 17% of the patients. CONCLUSION: MnDPDP-enhanced images can improve lesion detection in the liver and are helpful for lesion characterisation. To obtain optimal diagnostic information of liver lesions T2-weighted images are also valuable. MnDPDP is a safe contrast agent for MR imaging of liver lesions.

Adult↗

PubMed1997

MR imaging properties and pharmacokinetics of MnDPDP in healthy volunteers.

PURPOSE: Thirteen male volunteers were studied to evaluate the MR imaging properties and pharmacokinetics of 10 mM mangafodipir trisodium infusion (MnDPDP, Teslascan). MATERIAL AND METHODS: Doses of 5 and 10 mumol/kg b.w. were administered by bolus injection (< 1 min) to 5 subjects, and by infusion (20 min) to 8 subjects, with a 3-week wash-out between doses. Infusion subjects underwent MR imaging. RESULTS: At 1 h after infusion, the plasma concentration of Mn was reduced to approximately 15% of the maximum value. Fifteen to 20% of Mn was recovered in the urine, and 50-60% was recovered in the faeces. The rapid initial plasma clearance of Mn is consistent with both rapid tissue uptake and rapid renal elimination. Increases in signal intensity were apparent on T1-weighted images of the liver, pancreas, spleen, renal cortex and the renal medulla, but not in regions of the brain protected by an intact blood-brain barrier. Increases were seen in the choroid plexus and pituitary. Contrast-related adverse events, only flushing of moderate intensity, occurred in bolus injection subjects. CONCLUSION: At 5 and 10 mumol/kg, mangafodipir produces relatively long-lasting enhancement of several abdominal organs, including the liver, pancreas and kidney.

Adult↗

PubMed1997

Zinc balance in adolescent females consuming a low- or high-calcium diet.

There is increasing evidence that calcium intake up to the threshold amount (1480 mg/d) increases bone mass during growth. However, there is concern that such a high calcium intake may interfere with the utilization of other nutrients such as zinc, which is also important for skeletal development. The purpose of our study was to investigate the effect of long-term calcium supplementation on zinc utilization in 26 adolescent females (mean +/- SD age 11.3 +/- 0.5 y) during a 14-d period. Each day subjects consumed a metabolic diet containing 722 mg Ca and 6.3 mg Zn. Participants were randomly assigned to receive either a placebo or a calcium supplement containing 1000 mg supplemental Ca/d as calcium citrate malate. Supplementation began 15 wk before the balance period to allow for adaptation to the greater calcium intake. Mean (+/-SD) zinc balance (0.8 +/- 0.8 compared with 0.3 +/- 1.1 mg/d, P = 0.23), fecal zinc (4.3 +/- 0.6 compared with 4.7 +/- 1.4 mg/d, P = 0.27), urinary zinc (0.4 +/- 0.2 compared with 0.5 +/- 0.1 mg/d, P = 0.55), and net zinc absorption (21% compared with 15%, P = 0.33) were not significantly different between the high- and low-calcium groups. Our results suggest that increasing the recommended dietary allowance of calcium to 1500 mg/d as recommended by the National Institutes of Health consensus panel will not have adverse effects on zinc utilization in adolescent females.

Absorption↗

PubMed1997

Dissociation between the effect of nitrous oxide on spontaneous and reflexly evoked sympathetic activity in dogs.

We have examined the effect of nitrous oxide on spontaneous sympathetic activity and A delta- and C-fibre mediated somatosympathetic reflexes in renal nerves, evoked by supramaximal electrical stimulation of radial nerves in anaesthetized, paralysed dogs undergoing mechanical ventilation. In six preparations, nitrous oxide was administered at end-tidal concentrations of 10%, 30%, 50% and 70%, each for 20 min. Spontaneous renal sympathetic activity increased significantly to 147.8% and 151.2% of control values with 50% and 70% nitrous oxide, respectively (P < 0.05), but there were no significant changes in A delta and C reflexes. We conclude that the large increase in spontaneous sympathetic activity was dissociated from somatosympathetic reflexes which remained unchanged at these concentrations of nitrous oxide.

Anesthetics, Inhalation↗

PubMed1997

Significance of apoptosis in the temporal and stage-specific loss of germ cells in the adult rat after gonadotropin deprivation.

The major objectives of the present study were to document the temporal and stage-specific acceleration of germ cell apoptosis in adult rats after selective suppression of pituitary gonadotropins by GnRH antagonist (GnRH-A) treatment, and to examine the possibility that apoptosis is the sole mechanism of germ cell death in response to hormonal deprivation. Groups of adult male rats were given a daily injection of a vehicle for 14 days or GnRH-A (1.25 mg/kg BW) for 2, 5, 7, and 14 days. Analysis of testicular apoptotic DNA fragmentation revealed a detectable increase at Day 5 and a maximal increase at 14 days after treatment. In situ analysis of germ cell apoptosis fully corroborated the observed increase in the degree of DNA fragmentation with time and also revealed a stage-related activation of apoptosis of specific germ cells. A low incidence (0.06-0.09) of germ cell apoptosis (expressed as numbers per Sertoli cell) was detectable at stages I, IX-XI, and XII-XIV in control rats. Mean incidence of apoptotic germ cells specifically at stages VII-VIII increased significantly (0.40 +/- 0.06) by Day 5 and increased another 2.2-fold (over the 5-day treatment values) on Day 7 after GnRH-A treatment as compared to values in controls, where no apoptosis was detected. Significantly increased incidence of apoptosis at stages IX-XI (0.37 +/- 0.05) over control values (0.07 +/- 0.01) was noted by Day 7. Within the study paradigm, the highest number of dying cells occurred by Day 14, at which time a modest but significant (p < 0.05) increase in the incidence of apoptosis was also noted at stages I, II-IV, V-VI, and XII-XIV in comparison with control values. Stages VII-VIII and IX-XI still exhibited the higher number of cells undergoing apoptosis (0.97 +/- 0.22, and 1.03 +/- 0.22, respectively). Comparison between rates of apoptosis and cell degeneration measured at stages VII-VIII demonstrated an intimate association (r = 0.94; p < 0.001) between apoptosis and germ cell loss, strongly supporting the concept that germ cell death (at these stages) after removal of hormonal support in the adult rat occurs almost exclusively via apoptosis.

Animals↗

PubMed1997

Kinetics of E-selectin expression in surgical flaps.

During the ischemia/reperfusion phenomenon, adhesion molecules seem to play a critical role in the recruitment of neutrophils to sites of eventual tissue injury. E-selectin is an endothelium-derived molecule that mediates adhesion of neutrophils to activated endothelial cells. In vitro expression of E-selectin, after exposure to stimuli such as endotoxin, interleukin 1, or tumor necrosis factor alpha is maximal at 4 to 6 h, followed by a decline toward basal levels at 24 to 48 h. Characterizing the temporal expression of E-selectin in an in vivo model of skin flap ischemia-reperfusion would help to determine the optimal approach to eventual pharmacologic blockade. This intervention may prove therapeutically beneficial in attenuating flap injury. This study, using the standard porcine buttock skin flap model, was designed to evaluate immunohistochemically the expression of E-selectin in flaps subjected to (1) arterial ischemia (8 h)-reperfusion (18 h), (2) venous ischemia (8 h)-reperfusion (18 h), and (3) distal ischemia (26 h). Four flaps were examined per group, with 8 biopsies being collected sequentially over the 26-h study period from each flap. Blinded, semi-quantitative histologic scoring revealed the following results: (1) E-selectin is absent in normal porcine skin; (2) with arterial ischemia/reperfusion, E-selectin expression in flaps was maximal at 1 h of reperfusion, declining thereafter; (3) with venous ischemia/reperfusion, E-selectin expression peaked during the first hour of ischemia, with subsequent decline; and (4) within a flap designed to sustain distal ischemia, E-selectin expression is relatively more intense in regions of the flap distant from the vascular pedicle, and maximal at 6 h after flap elevation. Our conclusion, therefore, is that the kinetics of E-selectin expression within the tissues of porcine skin flaps differs depending on the type of ischemic insult sustained. Interpretation of these findings, correlating possible pathophysiologic differences in the different models of ischemia, is offered.

Animals↗

PubMed1997

Excitatory convergence of Y and non-Y information channels on single neurons in the PMLS area, a motion area of the cat visual cortex.

We analysed the receptive field properties of neurons in the posteromedial lateral suprasylvian (PMLS) visual cortical area of anaesthetized cats in which there was selective conduction block of the largest (Y-type) fibres in one optic nerve. As in normal cats, in cats with selective block of one optic nerve the great majority of PMLS cells could be activated by photic stimulation through either eye. However, the responses evoked by stimulation via the eye with the selectively pressure-blocked optic nerve ('Y-blocked eye') were significantly weaker than those of the same cells evoked by the stimulation via the normal eye. Accordingly, eye dominance histograms were shifted markedly in favour of the normal eye. Furthermore, there was a significant shift towards lower preferred velocities when PMLS cells were photically stimulated via the Y-blocked eye. Finally, when stimulated via the Y-blocked eye, PMLS cells responded poorly or not at all to high stimulus velocities (> or = 100 degrees/s). On the other hand, a number of receptive field properties, such as the spatial organization of receptive fields, the size of the discharge fields, orientation tuning and direction selectivity indices, were not significantly affected by the removal of the Y input. We conclude that virtually all neurons in the PMLS area of the cat receive excitatory input from both Y and non-Y information channels, although the Y channel provides the dominant input and makes the principal contribution to the detection of high-velocity motion.

Animals↗

PubMed1997

Neuropathogenesis of chimeric simian/human immunodeficiency virus infection in pig-tailed and rhesus macaques.

We recently reported that a chimeric simian/human immunodeficiency virus (SHIVKU-1) developed in our laboratory caused progressive depletion of CD4+ T lymphocytes and AIDS within 6 months of inoculation into pig-tailed macaques (M. nemestrina). None of the pig-tailed macaques showed productive SHIV infection in the central nervous system (CNS). In this report, we show that by further passage of the pathogenic virus in rhesus macaques [M. mulatta], we have derived a new strain of SHIV (SHIVKU-2) that has caused AIDS and productive CNS infection in 3 of 5 rhesus macaques infected with the virus. Productive replication of SHIV in the CNS was clearly shown by high infectivity titers and p27 protein levels in brain homogenates, and in 2 of the 3 rhesus macaques this was associated with disseminated, nodular, demyelinating lesions, including focal multinucleated giant cell reaction, largely confined to the white matter. These findings were reminiscent of HIV-1 associated neurological disease, and our immunohistochemical and in situ hybridization data indicated that the neuropathological lesions were associated with the presence of SHIV-specific viral antigens and nucleic acid respectively. However, the concomitant reactivation of opportunistic infections in these macaques suggested that such pathogens may have influenced the replication of SHIV in the CNS, or modified the neuropathological sequelae of SHIV infection in the rhesus species, but not in pig-tailed macaques. Our findings in the two species of macaques highlight the complexities of lentiviral neuropathogenesis, the precise mechanisms of which are still elusive.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Interactions of the RepA1 protein with its replicon targets: two opposing roles in control of plasmid replication.

By studying the interaction of derivatives of RepFIC miniplasmids, we were able to demonstrate that under certain conditions the RepA1 initiator protein inhibits plasmid replication. An analysis of cloned derivatives whose replication is inhibited by the RepA1 protein revealed the existence of two areas of the RepFIC genome that interact with RepA1 in the inhibition reaction. One of these areas, which occurs in the origin region, was explored by in vivo methylation protection footprinting studies. The protected area was 200 bp long and showed a definite periodicity of protected and hypersensitive sites, suggesting that RepA1 promotes a topological change in the RepFIC genome. The significance of our results is discussed in the context of plasmid replication control.

Bacterial Proteins↗

PubMed1997

Cloning and characterization of the major outer membrane protein gene (ompH) of Pasteurella multocida X-73.

The major outer membrane protein (OmpH) of Pasteurella multocida X-73 was purified by selective extraction with detergents, followed by size exclusion chromatography. The planar lipid bilayer assay showed that OmpH has pore-forming function. The average single channel conductance in 1.0 M KCl was 0.62 nS. The gene (ompH) encoding OmpH has been isolated and sequenced by construction of a genomic library and PCR techniques. The coding region of this gene is 1,059 bp long. The predicted primary protein is composed of 353 amino acids, with a 20-amino-acid signal peptide. The mature protein is composed of 333 amino acids with a molecular mass of 36.665 kDa. The ompH gene encoding mature protein has been expressed in Escherichia coli by using a regulatable expression system. The ompH gene was distributed among 15 P. multocida serotypes and strain CU. Protection studies showed that OmpH was able to induce homologous protection in chickens. These findings demonstrate that OmpH is a protective outer membrane porin of strain X-73 and is conserved among P. multocida somatic serotypes.

Amino Acid Sequence↗